@article {pmid41366440,
year = {2025},
author = {Soni, T and Gupta, S and Bharany, S and Rehman, AU and Ghoniem, RM and Taye, BM},
title = {Retinal vessel segmentation using multi scale feature attention with MobileNetV2 encoder.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {43369},
pmid = {41366440},
issn = {2045-2322},
abstract = {This work introduces the MSFAUMobileNet model, a complex U-Net structure tailored for retinal blood vessel segmentation, which is a critical process for detecting and monitoring retinal diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration (AMD). The model uses Multi-Scale Feature Aggregation (MSFA), Residual Connections, and Attention Mechanisms to enhance its segmentation accuracy. Utilizing MobileNetV2 as the encoder, the model is capable of effectively generating 13 bottleneck layers' worth of hierarchical features. Although residual connections and attention mechanisms are useful in improving the segmentation process and guaranteeing the precise outlining of intricate vascular networks, MSFA extracts spatial information at various resolutions. The model was tested on the DRIVE dataset and produced exceptionally high scores with accuracy at 99.99%, Dice coefficient at 99.95%, and Intersection over Union (IoU) at 99.94%. These scores show how efficiently the model separates the complex retinal network, enabling early treatment and detection of retinal disease. MSFAUMobileNet is a good medical image analysis software for real clinical practice owing to its computational speed and precision, particularly in the management of retinal disease.},
}
@article {pmid41362358,
year = {2026},
author = {Hinterhuber, L and Birner, K and Schrittwieser, J and Coulibaly, LM and Fuchs, P and Schürer-Waldheim, S and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U and Reiter, GS},
title = {Biomarker-Specific Test-Retest Repeatabilities of Microperimetry in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100978},
pmid = {41362358},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the biomarker-specific intradevice and interdevice repeatability of microperimetry (MP) examinations in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Cross-sectional study.<br><br>SUBJECTS: Twenty eyes of 20 individuals with nAMD.<br><br>METHODS: Patients underwent 2 consecutive MP assessments on the MP-3 (photopic) and Macular Integrity Assessment ([MAIA], mesopic), each in a randomized sequence. The pointwise sensitivity values were obtained using a 45-stimuli grid and were coregistered with the OCT volumes. Intraretinal fluid (IRF), subretinal fluid, and pigment epithelium detachment (PED) were quantified with deep learning, whereas subretinal hyperreflective material (SHRM) and ellipsoid zone (EZ) loss were manually annotated. Intradevice repeatability was assessed using Bland-Altman plots, coefficient of repeatability (CoR) and intraclass correlation coefficient. Differences in fixation stability and examination time were calculated using mixed-effect models.<br><br>MAIN OUTCOME MEASURES: Intradevice and interdevice repeatability and impact of OCT biomarkers on repeatability.<br><br>RESULTS: Analysis of a total of 3600 stimuli points revealed a CoR of &#xb1;6.37 decibel and &#xb1;5.68 for MP-3 and MAIA, respectively. Presence of OCT biomarkers had a significant impact on repeatability in the MP-3 for IRF (P < 0.0001), SHRM (P = 0.015), and EZ loss (P < 0.0001). Statistically significant results were obtained in the MAIA for IRF (P < 0.0001), PED (P < 0.0001), SHRM (P = 0.0005), and EZ loss (P < 0.0001). Intraclass correlation coefficients revealed excellent intradevice repeatability and good interdevice repeatability, ranging from 0.83 [95% confidence interval [CI]: 0.60-0.91] to 0.94 [95% CI: 0.93-0.94].<br><br>CONCLUSIONS: OCT biomarkers IRF, SHRM, and EZ loss significantly impacted repeatability under photopic and mesopic testing conditions with the MAIA also revealing a statistically significant association for PED. These findings demonstrate the viability of the MP devices to detect functional variability associated with nAMD biomarkers. Repeatability between consecutive MP tests in 2 commonly used MP devices showed good-to-excellent metrics in nAMD, which further supports the use of MP as a viable outcome measure in clinical trials and practice.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41361469,
year = {2025},
author = {Wang, X and Gui, S and Liu, X and Tao, Y and Gao, J and Liu, H},
title = {Eriocitrin inhibits sodium iodate-induced cuproptosis and barrier function impairment in retinal pigment epithelium via SIRT7/YAP/ATP7A pathway.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-025-07451-w},
pmid = {41361469},
issn = {1479-5876},
support = {2023zhyx-C72//the Research Fund Project of Anhui Institute of Translational Medicine/ ; },
abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is characterized by retinal pigment epithelium (RPE) barrier dysfunction, and currently lacks effective treatment options. Eriocitrin is a natural flavonoid with antioxidant and anti-inflammatory properties, and its potential role in inhibiting cuproptosis and improving RPE barrier function remains unclear.<br><br>METHODS: ARPE-19 cells treated with sodium iodate (NaIO&#x2083;) were used to establish an in vitro AMD model. The effects of eriocitrin at various concentrations (0-100 &#xb5;M) and treatment durations on cell viability were assessed using the CCK-8 assay. ELISA and ROS fluorescence were used to assess inflammation and oxidative stress levels. Western blotting and qPCR analysis were employed to evaluate the expression of copper-dependent programmed cell death (cuproptosis)-related markers. RPE barrier function was analyzed by transepithelial electrical resistance (TEER), FITC-dextran permeability assays, and the expression of tight junction proteins. We further utilized siRNA to knockdown SIRT7 and ATP7A gene, and pharmacological inhibition of YAP using verteporfin. In vivo, a NaIO&#x2083;-induced AMD model was established in both C57BL/6J and SIRT7 silencing mice, followed by administration of eriocitrin (25 or 50&#xa0;mg/kg). Retinal histology and protein expression were subsequently analyzed.<br><br>RESULTS: Eriocitrin significantly ameliorated NaIO&#x2083;-induced reductions in cell viability, decreased ROS levels, and suppressed inflammatory cytokine expression. It also restored RPE barrier function in a dose-dependent manner. Mechanistically, eriocitrin modulated SIRT7 expression, inhibited YAP activity, and enhanced ATP7A expression. Genetic silencing or knockdown of SIRT7 markedly weakened the protective effects of eriocitrin, including its antioxidant and barrier-restoring functions. YAP inhibition by verteporfin partially mimicked the actions of eriocitrin, while ATP7A silencing completely abrogated its effects, indicating that the SIRT7/YAP/ATP7A axis plays a crucial role in the therapeutic mechanism of eriocitrin against AMD.<br><br>CONCLUSION: This study demonstrated that eriocitrin alleviates NaIO&#x2083;-induced oxidative stress and RPE barrier dysfunction by modulating the SIRT7/YAP/ATP7A signaling pathway and inhibiting cuproptosis. Our findings indicated eriocitrin as a promising natural therapeutic candidate for dry AMD and lay the foundation for developing flavonoid-based anti-cuproptosis strategies.},
}
@article {pmid41361163,
year = {2025},
author = {Farashi, S and Abbott, CJ and Ansell, BRE and Wu, Z and Altay, L and Arnon, E and Arnould, L and Bagdasarova, Y and Balaskas, K and Chen, FK and Chew, E and Chowers, I and Clarke, S and Cukras, C and Delcourt, C and Delyfer, MN and den Hollander, AI and Fauser, S and Finger, RP and Gabrielle, PH and Han, J and Hodgson, LAB and Hogg, R and Holz, FG and Hoyng, C and Kumar, H and Lad, EM and Lee, A and Luhmann, UFO and Mauschitz, MM and McKnight, AJ and McLenachan, S and Mishra, A and Moghul, I and Orozco, LD and Sampson, DM and Scott, LW and Sitnilska, V and Song, S and Stockwell, A and Swaroop, A and Terheyden, JH and Tiosano, L and Tufail, A and Yaspan, BL and , and , and Pébay, A and Fletcher, EL and Guymer, RH and Bahlo, M and , },
title = {HTRA1/lncRNA HTRA1-AS1 dominates in age-related macular degeneration reticular pseudodrusen genetic risk with no complement involvement.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10854},
pmid = {41361163},
issn = {2041-1723},
support = {GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1195236//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Independent Research Institute Infrastructure Support Scheme//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1157776//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT2008382//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1154389//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1194667//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT1181010//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Operational Infrastructure Support//Department of Health, State Government of Victoria (Victorian Department of Health)/ ; Operational Infrastructure Support//Department of Health, State Government of Victoria (Victorian Department of Health)/ ; Z01EY000546//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; },
mesh = {Humans ; *High-Temperature Requirement A Serine Peptidase 1/genetics ; *Macular Degeneration/genetics/pathology ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Aged ; Male ; Female ; *RNA, Long Noncoding/genetics ; Polymorphism, Single Nucleotide ; Retina/pathology/metabolism ; *Retinal Drusen/genetics ; Chromosomes, Human, Pair 10/genetics ; Chromosomes, Human, Pair 1/genetics ; Quantitative Trait Loci ; Middle Aged ; Aged, 80 and over ; Proteins/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2165 AMD+/RPD+ and 4181 AMD+/RPD- compared to 7639 control participants, both chromosomes 1 (CFH) and 10 (ARMS2/HTRA1) major AMD risk loci are reidentified. However association is only detected for the chromosome 10 locus when comparing AMD+/RPD+ to AMD+/RPD- cases. The chromosome 1 locus is notably absent. The chromosome 10 RPD risk region contains a long non-coding RNA HTRA1-AS1 (ENSG00000285955/BX842242.1) which colocalizes with genetic markers of retinal thickness. HTRA1-AS1 has a strong retinal eQTL signal, pinpointing the parafoveal photoreceptor outer segment layer. Whole genome sequencing of phenotypically extreme RPD cases identifies even stronger enrichment for the chromosome 10 risk genotype.},
}
@article {pmid41358132,
year = {2025},
author = {Pashandi, Z and Liu, M and Azam, M and Das, S and Sheves, M and Jastrzebska, B},
title = {Therapeutic Potential of Partial Retinoid Agonists against Vertebrate Rhodopsin Misfolding Disorders.},
journal = {ACS omega},
volume = {10},
number = {47},
pages = {57487-57502},
pmid = {41358132},
issn = {2470-1343},
abstract = {Mutations in rod opsin are a leading cause of inherited retinal degenerative diseases such as retinitis pigmentosa (RP). Pharmacological compounds that stabilize rhodopsin (Rho) and mitigate cellular stress pathways hold promise for therapeutic intervention. Among these, retinoid analogs have shown efficacy in models of autosomal dominant RP (adRP) and age-related macular degeneration (AMD). In this study, we evaluated the pharmacological potential of two partial retinoid agonists, acyclic-retinal and 9-cis-9-demethyl-retinal, as well as newly synthesized retinol and amine derivatives of 9-cis-9-demethyl-retinal. A photoreceptor-derived 661W cell line stably expressing two RP-linked misfolding rod opsin mutants, P23H and T289P, was used to assess the compound activity. We investigated the effects on opsin folding, glycosylation, membrane localization, and pigment regeneration. Both acyclic-retinal and 9-cis-9-demethyl-retinal promoted mature glycosylation and enhanced cell surface trafficking of P23H and T289P rod opsins. Spectroscopic analysis confirmed that these compounds regenerated functional, photosensitive pigments and stabilized the receptor in the Meta-I conformation upon light exposure. Notably, 9-cis-9-demethyl-retinal exhibited higher binding affinity than 9-cis-retinal, without impairing visual signaling postphotoisomerization. Among the derivatives, the amine form of 9-cis-9-demethyl-retinal was most effective in promoting proper folding and localization of misfolded rod opsin, outperforming the corresponding retinol analog. These findings support the therapeutic potential of acyclic-retinal, 9-cis-9-demethyl-retinal, and its derivatives for rescuing misfolded rod opsin and delaying photoreceptor degeneration in RP.},
}
@article {pmid41356765,
year = {2025},
author = {Warner, JD and Tuli, A and Zhang, DD and Singireddy, R and Ebrahimiadib, N and Chen, J},
title = {Full-Spectrum Pachychoroid Manifestation in One Eye: A Case Report.},
journal = {Case reports in ophthalmology},
volume = {16},
number = {1},
pages = {896-902},
pmid = {41356765},
issn = {1663-2699},
abstract = {INTRODUCTION: The pachychoroid spectrum refers to a group of chorioretinal disorders including pachychoroid pigment epitheliopathy (PPE), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC). These conditions are thought to represent progressive stages, beginning with subclinical retinal pigment epithelium (RPE) changes in PPE, advancing to serous retinal detachment in CSC, followed by choroidal neovascularization in PNV, and culminating in aneurysmal dilation of vessels in PCV. We present a rare case of the pachychoroid spectrum in which lesions in all four stages were simultaneously observed in a single, fovea-sparing eye.<br><br>CASE PRESENTATION: An 85-year-old man presented with a 1-month history of a visual disturbance in his left eye. Examination revealed all four stages of pachychoroid disease in the same eye: choroidal neovascular membrane (CNV) with subretinal hemorrhage (pachychoroid neovascularization, PNV), multiple RPE defects (PPE), and findings consistent with CSC and PCV. He was treated with a combination of anti-VEGF injections and focal laser therapy with the lesions stabilizing after 2 years.<br><br>CONCLUSION: Although it has features similar to age-related macular degeneration, pachychoroid spectrum is a distinct disease entity, with a slower onset and greater response to initial therapy. It may necessitate therapies otherwise not used for other causes of neovascularization like focal laser treatment and verteporforin photodynamic therapy. It is a unique pathologic process presenting with varying stages/lesions that have distinct morphological features but are thought to be a part of the same spectrum.},
}
@article {pmid41356440,
year = {2025},
author = {Mimura, T and Noma, H},
title = {Metabolites of traffic-related volatile organic compounds in age-related macular degeneration.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e20405},
pmid = {41356440},
issn = {2167-8359},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Macular Degeneration/urine/metabolism ; Aged ; *Volatile Organic Compounds/urine/metabolism ; *Vehicle Emissions/analysis/toxicity ; Middle Aged ; *Air Pollutants/adverse effects ; Gas Chromatography-Mass Spectrometry ; Aged, 80 and over ; Case-Control Studies ; },
abstract = {BACKGROUND: Volatile organic compounds (VOCs), commonly emitted from vehicle exhaust and industrial activities, are prevalent air pollutants in urban environments. These compounds have been reported to cause various health effects through mechanisms such as oxidative stress and neurotoxicity. Recently, air pollution has attracted attention as a potential risk factor for age-related macular degeneration (AMD); however, the association between VOC exposure and AMD remains unclear.<br><br>OBJECTIVE: This study aimed to assess VOC exposure levels among urban-dwelling AMD patients by quantifying urinary metabolites and investigating the association between VOCs and AMD.<br><br>METHODS: This cross-sectional study included 40 untreated AMD patients (AMD group), 10 cataract patients (Cataract group), and 10 healthy controls (Healthy group). Representative urinary metabolites of VOCs-2-methylhippuric acid, 3-methylhippuric acid, mandelic acid, phenylglyoxylic acid, and trans,trans-muconic acid-were measured using gas chromatography-mass spectrometry (GC/MS), with concentrations corrected for urinary creatinine. Group comparisons were performed based on creatinine-adjusted metabolite levels.<br><br>RESULTS: The AMD group exhibited elevated urinary VOC metabolite levels compared to both control groups. The ratios of mean concentrations in the AMD group versus the Healthy and Cataract groups, respectively, were: 2-methylhippuric acid (201% and 181%), 3-methylhippuric acid (190% and 139%), mandelic acid (304% and 198%), phenylglyoxylic acid (118% and 90%), and trans,trans-muconic acid (214% and 92%). Among these, 2-methylhippuric acid and mandelic acid were significantly higher in the AMD group than in both controls (p&#xa0;<&#xa0;0.001 and p&#xa0;=&#xa0;0.042; p&#xa0;<&#xa0;0.001, respectively). Trans,trans-muconic acid also showed a significant increase compared to the Healthy group (p&#xa0;<&#xa0;0.001). Correlation analysis within the AMD group revealed moderate but significant associations for 2-methylhippuric acid (r&#xa0;=&#xa0;0.29, p&#xa0;=&#xa0;0.011), mandelic acid (r&#xa0;=&#xa0;0.47, p&#xa0;<&#xa0;0.001), and trans,trans-muconic acid (r&#xa0;=&#xa0;0.27, p&#xa0;=&#xa0;0.020). Multivariate logistic regression identified mandelic acid as an independent factor significantly associated with AMD (odds ratio = 17.20, p&#xa0;<&#xa0;0.001). Subgroup analysis categorized the AMD group into drusenoid AMD, typical AMD (t-AMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). No significant differences in urinary VOC metabolite levels were observed among the four subtypes after multiple comparison adjustment.<br><br>CONCLUSIONS: These findings indicate that AMD patients are exposed to higher levels of traffic-related VOCs. While mandelic acid-a styrene metabolite-was independently associated with AMD, its role should be interpreted as a potential exposure marker rather than a definitive disease biomarker. Further longitudinal studies are warranted to clarify causal relationships between VOC exposure and AMD development.},
}
@article {pmid41354925,
year = {2025},
author = {Nafar, H and Mahdavi Sharif, P and Rezaei, N},
title = {Advances in nanomedicine-based retinal drug delivery: mechanisms and translational applications.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-025-03848-3},
pmid = {41354925},
issn = {1477-3155},
abstract = {Retinal diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), alongside optic neuropathies such as glaucoma, are primary contributors to irreversible visual impairment and blindness, and not only impact the quality of life but also place considerable socioeconomic pressures on healthcare systems worldwide. Despite the availability of several therapeutic modalities, the clinical management of these conditions remains challenging due to the unique anatomical and physiological barriers of the eye (i.e., tear film, cornea, blood-aqueous barrier, and the blood-retinal barrier), which impede achieving therapeutic drug concentrations in the posterior segment. Topical administration exhibits low bioavailability, while systemic delivery is generally inefficient and associated with adverse effects. Intravitreal injections (IVIs) deliver drugs directly to the vitreous but necessitate frequent administration, hence increasing risks of endophthalmitis, retinal detachment, and patient non-compliance. Nanomedicine has revolutionized drug delivery science across various medical fields, offering significant advantages for therapeutic interventions. Nanoparticle (NP)-based systems enhance drug solubility and stability, improve pharmacokinetic profiles, facilitate passage across biological barriers, and enable targeted delivery to specific cells or tissues with surface modifications, thereby potentially increasing bioavailability while minimizing systemic toxicity. This review aims to illustrate recent advancements in the design principles, preclinical applications, and translational potential of NP-based drug delivery systems aimed at addressing the challenges inherent in treating posterior segment eye diseases. NPs (ranging from polymeric and lipid-based systems to inorganic and hybrid forms) have been able to effectively carry various formulations of antiangiogenic, anti-inflammatory, anti-neoplastic, and antioxidant compounds, as well as genetic materials, to counteract such disorders. NP's size, surface charge, and composition can be modulated to optimize interaction with ocular tissues and overcome barriers. With their controlled and sustained drug release, NPs decrease the required frequency of IVIs. In addition, NPs can encapsulate a wide range of therapeutic agents (including hydrophobic molecules, proteins, and nucleic acids) and are amenable to the functionalization of their surfaces with ligands for specific receptors on retinal cells, thereby enhancing therapeutic efficacy and minimizing local toxicities. The findings of this review will establish a research agenda for translating NP-based interventions into clinical practice.},
}
@article {pmid41354398,
year = {2025},
author = {Fernández, Y and Subirada, PV and Vaglienti, MV and Tovo, A and Paz, MC and Barcelona, PF and Sánchez, MC},
title = {GLIAL FIBRILLARY ACIDIC PROTEIN, AN EARLY AND SUSTAINED INDICATOR OF RETINOPATHY PROGRESSION.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110796},
doi = {10.1016/j.exer.2025.110796},
pmid = {41354398},
issn = {1096-0007},
abstract = {Macroglial cells, particularly astrocytes and Müller glial cells (MGCs), are crucial for maintaining retinal health and function. Both cell types express glial fibrillary acidic protein (GFAP), although their expression levels and patterns differ. In a healthy retina, astrocytes constitutively express GFAP, whereas MGCs typically show low or undetectable levels. In response to retinal insults, macroglial cells are activated through a process known as gliosis to preserve retinal homeostasis. The gliotic response includes cellular hypertrophy and the upregulation of intermediate filaments -primarily GFAP- as a protective mechanism. However, when harmful stimuli persist, both astrocytes and MGCs may contribute to pathology, becoming associated with ongoing damage and loss of retinal function. Changes in GFAP expression have been described in conditions like diabetic retinopathy, sickle-cell retinopathy, and age-related macular degeneration, indicating retinal stress and dysfunction. A deeper understanding of GFAP's dual role in retinal diseases is critical for developing effective treatments for these conditions and for identifying its potential as a biofluid-based biomarker.},
}
@article {pmid41354182,
year = {2025},
author = {Xu, L and Chen, ZA and Wu, CH and Chen, YP and Wu, SH and Mou, CY and Tseng, CL and Chien, Y and Chan, HW and Yang, TC and Chiou, SH},
title = {Dual-Functionalized Mesoporous Silica Nanoparticles for Topical Axitinib Delivery to the Posterior Eye Segment.},
journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences},
volume = {},
number = {},
pages = {107398},
doi = {10.1016/j.ejps.2025.107398},
pmid = {41354182},
issn = {1879-0720},
abstract = {Topical drug delivery to the posterior eye segment remains a significant challenge due to ocular anatomical barriers, particularly in diseases such as wet age-related macular degeneration (AMD), where treatment typically relies on frequent intravitreal (IVT) injections of anti-angiogenic agents. In this study, we present a non-invasive eye drop formulation of axitinib (AXT), a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, encapsulated within 25-nm dual-functionalized mesoporous silica nanoparticles (AXT@dual-MSNs) engineered for efficient retinal delivery. The nanoparticles feature sulfonate-functionalized mesopores that enhanced AXT loading and solubilization, along with a PEGylated/quaternary ammonium-modified surface that improved colloidal stability and favored intramesopore drug confinement. Following topical administration, AXT@dual-MSNs achieved retinal accumulation via the conjunctiva-sclera-choroid pathway, effectively bypassing the corneal route. A pharmacokinetic analysis confirmed rapid, transscleral delivery of AXT with therapeutically relevant concentrations in the retina. In a laser-induced choroidal neovascularization (CNV) mouse model, a well-established surrogate for wet AMD, AXT@dual-MSN eyedrops significantly suppressed neovascular lesion formation, outperforming free-drug eyedrops and IVT AXT injection. Notably, the formulation exhibited excellent ocular tolerance, with no evidence of local toxicity or contralateral eye exposure. This work introduces a novel nanocarrier system capable of overcoming the longstanding delivery barrier to the posterior eye segment via eyedrops, offering a safe, effective, and clinically translatable alternative to IVT injections. The modular design of AXT@dual-MSNs also holds promise for expanding topical access to other hydrophobic or labile therapeutics targeting retinal diseases.},
}
@article {pmid41353670,
year = {2025},
author = {Poteet, J and Koetting, C and Vakharia, PS},
title = {Role of B Vitamins in Preventing the Development and Progression of Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41353670},
issn = {2193-8245},
support = {Editorial/writing assistance//Bausch + Lomb/ ; Funding for rapid service fee//Bausch + Lomb/ ; },
abstract = {No current treatments are curative for age-related macular degeneration (AMD), and preventing disease progression is challenging. Dietary factors play a role in the course of macular degeneration, and management of AMD commonly includes nutraceuticals (e.g., supplementation with a combination of antioxidant vitamins and minerals). This commentary summarizes the existing literature, emerging evidence, and upcoming research on the role of B vitamins in both preventing the development of AMD and slowing its progression.},
}
@article {pmid41353467,
year = {2025},
author = {E de Carlo Forest, T and Marin, AI and Gill, Z and Gnanaraj, R and Patnaik, JL and Poppelaars, F and Lynch, AM and Palestine, AG and Mathias, MT and Manoharan, N and Frazer-Abel, AA and Holers, VM and Mandava, N},
title = {Association between systemic complement levels and choroidal thickness in advanced non-neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-31051-9},
pmid = {41353467},
issn = {2045-2322},
support = {R01EY032456//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; UL1 TR002535/TR/NCATS NIH HHS/United States ; },
abstract = {To investigate associations between systemic complement activation and choroidal thickness (CT) in advanced non-neovascular age-related macular degeneration (nnAMD). Cross-sectional study of 96 patients (187 eyes) with advanced nnAMD enrolled in the University of Colorado AMD Registry (August 2014-June 2021). Medical histories, multimodal imaging, and plasma samples were collected. Plasma was analyzed via enzyme-linked immunosorbent assay and multiplex Luminex assays for complement factors C1q, monoclonal B-cell lymphocytosis, C2, C4, C4b, C3, C3a, Factor B, Bb, Factor D, Factor H, Factor I, C5 and soluble C5b-9. CT was measured subfoveally and at 1000 μm intervals superiorly, inferiorly, nasally, and temporally using Spectralis OCT. Linear modeling with generalized estimating equations assessed log-transformed OCT and complement factors. The mean age was 82.2 years (± 7.1 SD); 54.2% were female. Average CT was negatively associated with Bb (β=-0.47, SE: 0.12, p = 0.0001) and the Bb/Factor B ratio (β=-0.28, SE: 0.12, p = 0.02), but not other complement markers. Bb levels correlated with alternative pathway components but not with classical or lectin pathway markers. We found a key association between systemic complement activation of Factor B and choroidal thickness in patients with advanced nnAMD, implying the potential involvement of the systemic alternative pathway in nnAMD patients.},
}
@article {pmid41352581,
year = {2025},
author = {Dinah, C and Esmaeelpour, M and Rachitskaya, AV and De Salvo, G and Munk, MR},
title = {Functional endpoints in patients with geographic atrophy: What to consider when designing a clinical trial.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101421},
doi = {10.1016/j.preteyeres.2025.101421},
pmid = {41352581},
issn = {1873-1635},
abstract = {There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure-function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.},
}
@article {pmid41352549,
year = {2025},
author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Wang, X},
title = {SS-OCTA versus ICGA: A Comparison of Detection Efficiency for Large Choroidal Vein Patterns in AMD Patients.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105303},
doi = {10.1016/j.pdpdt.2025.105303},
pmid = {41352549},
issn = {1873-1597},
abstract = {PURPOSE: To compare the efficacy of swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in visualizing and classifying large choroidal vein topography, and to evaluate the association between specific venous patterns and pachychoroid spectrum disease (PSD)-associated macular neovascularization (MNV).<br><br>METHODS: This retrospective cross-sectional study included 222 eyes from 160 patients with neovascular age-related macular degeneration (nAMD). All participants underwent both SS-OCTA and ICGA imaging. Choroidal venous patterns were classified into four types based on ICGA venous phase images: watershed, anastomotic, upper thicker, and lower thicker. SS-OCTA images were processed and analyzed using Fiji software. Diagnostic agreement between modalities was assessed using Cohen's Kappa. Logistic regression was used to evaluate the association between venous patterns and disease subtypes.<br><br>RESULTS: SS-OCTA and ICGA showed almost perfect agreement in classifying choroidal venous patterns in discernible cases (unweighted Kappa&#x202f;=&#x202f;0.978). Among 77 eyes where ICGA failed to provide a clear classification, SS-OCTA achieved a definitive diagnosis in 87.0% (P < 0.001), with the anastomotic type being the most common. Furthermore, the watershed pattern was significantly more prevalent in non-PCV nAMD compared to PCV (29.8% vs. 12.1%, p&#x202f;=&#x202f;0.002), suggesting distinct choroidal venous backgrounds between these subtypes.<br><br>CONCLUSION: SS-OCTA provides a reliable, non-invasive alternative to ICGA for visualizing and classifying large choroidal veins, with superior performance in cases obscured by hemorrhage or leakage. The distinct distribution of venous patterns across nAMD subtypes highlights the potential role of choroidal venous architecture in disease phenotyping and pathogenesis.},
}
@article {pmid41352547,
year = {2025},
author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Zhang, S},
title = {Multimodal and 3D Imaging Presentation of the Evolution of Pressure-Related CNV.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105305},
doi = {10.1016/j.pdpdt.2025.105305},
pmid = {41352547},
issn = {1873-1597},
abstract = {This study reports a unique case that visually demonstrates the six-year evolution of a pressure-related choroidal neovascularization (CNV) using multimodal image registration and three-dimensional (3D) reconstruction. A 65-year-old female with neovascular age-related macular degeneration received 33 anti-VEGF injections over six years but experienced continued vision decline. Through precise registration of indocyanine green angiography, and optical coherence tomography angiography images, combined with 3D modeling of swept-source OCTA volume data. We found that the main trunk of this large, tree-like type II CNV originated from an abnormally dilated great vein, which exhibited an anastomosis with an accompanying great vein. Furthermore, the 3D reconstruction viewed from the scleral side revealed that this vein was closely opposed to and shared a shunt branch with an underlying choroidal great artery. The CNV appeared to function as a "pressure-relief valve," sprouting from the venous trunk to alleviate pressure. This case underscores the critical role of deep multimodal imaging integration in tracing CNV origins and reveals that some anti-VEGF-resistant CNVs may represent hemodynamic compensatory disorders secondary to pre-existing large vessel structural abnormalities, rather than purely neovascular diseases.},
}
@article {pmid41350762,
year = {2025},
author = {Ma, Y and Zan, H and Li, L and Li, S and Yu, X and Li, J and Cai, J and Zhang, H and Yang, J and Zhang, R and Salvi, R and Li, W and Wang, H and Yin, S},
title = {Global burden and geospatial drivers of sensory impairment with sense organ disease projections to 2050.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-025-01259-x},
pmid = {41350762},
issn = {2730-664X},
support = {82271161//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82330034//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {BACKGROUND: Sense organ diseases represent the leading causes of years lived with disability. Despite its major impact, a comprehensive understanding of sense organ diseases burden remains limited.<br><br>METHODS: Based on the data from the Global Burden of Disease Study 2021 and nighttime light exposure data from remote-sensing satellites, we did secondary analysis and described the epidemiological characteristics of sense organ diseases globally and nationally. The relationship between the specific causes of blindness and vision loss and nighttime light exposure was further explored. We assessed the trends, causes and cross-country inequalities related to sense organ diseases and forecasted the burden of disease until 2050.<br><br>RESULTS: Here we show that in 2021, there are more than 2 billion prevalent cases and more than 77 million years lived with disability cases of sense organ diseases globally. Both age-related macular degeneration and near vision loss show positive correlations with nighttime light exposure. The global burden of sense organ diseases continues to rise from 1990 to 2021, primarily driven by population growth and ageing. Health inequalities exist between different countries and increase over time. Projections of years lived with disability for sense organ diseases from 2022 to 2050 show that although the age-standardized rate remains stable, the number increases significantly.<br><br>CONCLUSIONS: Over the past 32 years, the global burden of sense organ diseases has increased, and cross-country inequalities have intensified due to the trends of population growth and aging. Therefore, it is urgently necessary to formulate more targeted and effective prevention and management strategies.},
}
@article {pmid41350718,
year = {2025},
author = {Ruiz-Medrano, J and Pana, I and García-Zamora, M and Flores-Moreno, I and Puertas, M and Ruiz-Moreno, JM},
title = {Faricimab treat-and-extend approach for neovascular age-related macular degeneration: insights from real-world clinical practice.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00776-0},
pmid = {41350718},
issn = {2056-9920},
abstract = {PURPOSE: To evaluate the clinical outcomes of the switch to faricimab in a treat-and-extend (T&amp;E) regimen patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective cohort study included consecutive patients with nAMD who had previously been treated with anti-VEGF agents in a T&amp;E regimen, with treatment intervals (TI) that could not be extended beyond 12 weeks, and a minimum follow-up of 24 weeks. These patients were switched to faricimab therapy in a T&amp;E regimen for at least 6 months. The primary endpoint was the TI between intravitreal injections (IVIs), and the secondary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to the last follow-up visit (LFUV).<br><br>RESULTS: A total of 225 eyes from 188 patients were included, with a mean age of 79.6&#x2009;&#xb1;&#x2009;7.4 years. Previous anti-VEGF treatments included ranibizumab (n&#x2009;=&#x2009;34), aflibercept (n&#x2009;=&#x2009;144), brolucizumab (n&#x2009;=&#x2009;6), and bevacizumab (n&#x2009;=&#x2009;41). TI1 (5.9&#x2009;&#xb1;&#x2009;2.0 weeks) matched the prior treatment interval. Significant increases in treatment intervals were observed at subsequent time points (TI2: 8.2&#x2009;&#xb1;&#x2009;3.2 weeks, TI3: 10.1&#x2009;&#xb1;&#x2009;3.9 weeks, TI4: 10.7&#x2009;&#xb1;&#x2009;4.3 weeks, TI5: 9.9&#x2009;&#xb1;&#x2009;4.0 weeks, and TI6: 8.5&#x2009;&#xb1;&#x2009;4.4 weeks; p&#x2009;<&#x2009;0.001). BCVA remained stable, going from 0.41&#x2009;&#xb1;&#x2009;0.23 to 0.43&#x2009;&#xb1;&#x2009;0.24 (p&#x2009;=&#x2009;0.0112). The mean number of injections was 5.9&#x2009;&#xb1;&#x2009;1.9, with a mean follow-up duration of 51.4&#x2009;&#xb1;&#x2009;11.8 weeks.<br><br>CONCLUSIONS: The switch to faricimab in a T&amp;E regimen significantly increased treatment intervals maintaining BCVA in patients with nAMD under other anti-VEGF treatments. No serious adverse events were reported. Longer follow-up is needed to confirm these results.},
}
@article {pmid41349782,
year = {2025},
author = {Horrigan, WF and Caron, Q and Rodriguez, A and Singh, R and Anand-Apte, B},
title = {The Effect of Age on Wound Healing in the Laser Induced Choroidal Neovascularization Model.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110790},
doi = {10.1016/j.exer.2025.110790},
pmid = {41349782},
issn = {1096-0007},
abstract = {The laser induced model of choroidal neovascularization (LiCNV) is a commonly used in vivo rodent model to study neovascular age-related macular degeneration (nAMD), although progression of this model is not well understood. In this study we characterize and compare the longitudinal progression of wound healing of laser induced choroidal neovascular (CNV) lesions in young and old mice. Using 2-month and 12-month-old C57BL/6J mice and ocular computerized tomography (OCT), fluorescein and indocyanine green angiography we performed a longitudinal imaging analysis at 3-, 7-, 14- and 28-days following laser injury. This was compared with immunohistochemical analysis of the lesions at similar timepoints for markers of angiogenesis, fibrosis, epithelial-to-mesenchymal transition (EMT), and gliosis. OCT analysis determined an increased lesion volume in older mice. In contrast younger mice demonstrated earlier vascularization and fibrosis with no difference in neovascularization or leakage. Reactive gliosis occurs directly above the laser-induced CNV lesion in both ages. The RPE in this model encloses the lesion area by day 14 in both young and old mice. This study concludes that age is an important variable in some but not all aspects of laser-induced CNV.},
}
@article {pmid41348407,
year = {2025},
author = {Hang, Z and Li, Y and Ren, W and Du, H},
title = {The blood-retinal barrier in ocular pathologies: an updated narrative review.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {10},
pmid = {41348407},
issn = {1573-2630},
mesh = {Humans ; *Blood-Retinal Barrier/physiopathology/pathology ; *Retinal Diseases/physiopathology ; *Eye Diseases/physiopathology ; },
abstract = {PURPOSE: To provide a comprehensive overview of the structural and functional characteristics of the blood-retinal barrier (BRB), examine its critical role in the pathogenesis of major ocular diseases, and summarize current and emerging therapeutic strategies aimed at restoring BRB integrity.<br><br>METHODS: A literature search was conducted in PubMed, Scopus, and Web of Science databases, focusing primarily on publications from the past 10 years supplemented by seminal earlier works. This narrative review synthesizes evidence on BRB molecular anatomy, pathological mechanisms, disease-specific roles, and therapeutic interventions.<br><br>RESULTS: The BRB comprises inner (iBRB) and outer (oBRB) compartments with distinct cellular and molecular architectures. BRB dysfunction is driven by convergent mechanisms including aging, hyperglycemia, oxidative stress, inflammation, and hypoxia, which disrupt tight junction proteins and promote aberrant angiogenesis. This barrier breakdown constitutes a pivotal pathogenic driver in major blinding diseases: age-related macular degeneration, diabetic retinopathy and retinal vein occlusion, glaucoma, and uveitis. Current standard treatments include anti-VEGF agents and corticosteroids. Emerging strategies target Wnt/&#x3b2;-catenin signaling, employ senolytic therapies, utilize biomaterial-based drug delivery, and develop organ-on-a-chip models for personalized medicine.<br><br>CONCLUSIONS: BRB disruption represents a critical inflection point in ocular disease progression, triggering self-perpetuating cycles of neuroinflammation and degeneration. Effective restoration requires multi-faceted approaches combining anti-angiogenic, antiinflammatory, and barrier-strengthening mechanisms. Future research should focus on dynamic functional assessment, single-cell multi-omics integration, and adaptive therapeutic strategies to prevent irreversible vision loss.},
}
@article {pmid41348378,
year = {2025},
author = {Wang, S and Hong, Y and Qu, Y and Zheng, K and Luo, H and Chen, R and Jia, H and Liu, X and Sun, X},
title = {Association between low handgrip strength and the increased risk of age-related macular degeneration: results from UK biobank cohort study.},
journal = {Aging clinical and experimental research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40520-025-03208-z},
pmid = {41348378},
issn = {1720-8319},
abstract = {OBJECTIVES: To determine whether handgrip strength is associated with the incidence of age-related macular degeneration.<br><br>METHODS: A prospective cohort study of over 500 thousand UK Biobank participants aged 40-69 years. Individuals&#x2009;&#x2265;&#x2009;50 years and without age-related macular degeneration at baseline were included. Exposure was the handgrip strength measured by dynamometer. Primary outcome was the incidence of age-related macular degeneration during 13 years of follow-up. Cox proportional-hazard models were fitted to estimate the risk effect for handgrip strength on age-related macular degeneration, and stratified for sociodemographic and lifestyle factors. Mediation models were regressed to explore underlying mechanisms driven by inflammatory and erythrocyte-related biomarkers.<br><br>RESULTS: 382174 eligible participants in the UK Biobank were included. After 4680431 person-year, 7987 individuals (2.09%) developed age-related macular degeneration. Individuals in the lowest quintile of handgrip strength had higher risk of age-related macular degeneration incidence (Hazard Ratio, 1.25; 95% CI, 1.16-1.35) compared with those in the highest quintile. Per 5&#xa0;kg decrement in handgrip strength was associated with increased risk of age-related macular degeneration incidence (Hazard Ratio, 1.06; 95% CI, 1.04-1.08) with similar trend among all subgroups except for sex. Specific inflammatory and erythrocyte-related biomarkers partially (37.5%) mediated the incidence of age-related macular degeneration as substantial biological mechanisms following handgrip strength decrease.<br><br>CONCLUSIONS: Our findings suggest that handgrip strength is associated with the incidence of age-related macular degeneration under the mediation of systemic proinflammatory factors. The current study holds an outlook for improved visual health over the evaluation and intervention of muscle strength in old-age population.},
}
@article {pmid41348248,
year = {2025},
author = {Bartol-Puyal, FA and Sánchez Monroy, J and Puzo Bayod, M and Mallén, V and Méndez-Martínez, S and Calvo, P and Pablo, L},
title = {Choroidal changes after antiVEGF in neovascular age-related macular degeneration with type 1 and 3 macular neovascularization.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {8},
pmid = {41348248},
issn = {1573-2630},
mesh = {Humans ; Retrospective Studies ; Male ; *Choroid/pathology ; Tomography, Optical Coherence/methods ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; Fluorescein Angiography/methods ; Aged, 80 and over ; Visual Acuity ; Follow-Up Studies ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage ; *Bevacizumab/administration &amp; dosage ; Middle Aged ; *Choroidal Neovascularization/drug therapy/diagnosis ; },
abstract = {PURPOSE: To analyze choroidal thickness (CT) in patients with neovascular age-related macular degeneration (nAMD) with type 1 macular neovascularization (MNV) and type 3 (or retinal angiomatous proliferation) after antiVEGF treatment for two years.<br><br>METHODS: Retrospective study enrolling Caucasian na&#xef;ve patients with nAMD (type 1 MNV), and patients with type 3 MNV with no other ophthalmological disorders, and without switching treatment. Nine manual CT measurements were performed on optical coherence tomography (OCT) Spectralis (Heidelberg Engineering). Demographic data, smoking, disease activity, and number of injections, among others were recorded. Three visits were analyzed: pretreatment baseline visit, first and last visits with no disease activity.<br><br>RESULTS: 53 eyes of 53 patients with type 1 MNV, and 41 eyes of 41patients with type 3 MNV were analyzed. Both groups received the same number of injections (p&#x2009;=&#x2009;0.282). Type 3 MNV patients showed lower CT (between 143.29 and 174.17&#x3bc;m) than type 1 MNV patients (between 169.91 and 220.17&#x3bc;m) in the baseline visit, but differences disappeared in first and last visits. Choroidal thinning was only observed in type 1 MNV patients between baseline and first visit (p&#x2009;<&#x2009;0.05). In the las visit, they had a CT between 87 and 96% of baseline measurement. No other influencing factor was detected.<br><br>CONCLUSIONS: Patients with nAMD (type 1 MNV) have higher CT than patients with type 3. However, patients with type 1 MNV experience significant choroidal thinning, and CT is similar in both groups after antiVEGF treatment. Smoking, type of drusen or other OCT features have no influence in this reduction.},
}
@article {pmid41347874,
year = {2025},
author = {Trivizki, O and Wykoff, CC and Smoor, MA and Rabinovitch, D and Zhou, A and Cao, JA and Lechanteur, YTE and van den Heuvel, L and van Gool, AJ and Gloerich, J and Vergroesen, JE and Klaver, CCW},
title = {Effect of Pegcetacoplan on Aqueous Humor Proteome in Geographic Atrophy: A Prospective Exploration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {15},
pages = {24},
doi = {10.1167/iovs.66.15.24},
pmid = {41347874},
issn = {1552-5783},
mesh = {Humans ; *Aqueous Humor/metabolism ; *Geographic Atrophy/drug therapy/metabolism ; Prospective Studies ; Male ; Aged ; Female ; *Proteome/metabolism/drug effects ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Complement C3/antagonists &amp; inhibitors ; Proteomics/methods ; Aged, 80 and over ; Middle Aged ; },
abstract = {PURPOSE: Pegcetacoplan, a complement component 3 (C3) inhibitor, has recently received U.S. Food and Drug Administration approval for treating geographic atrophy (GA), an advanced stage of age-related macular degeneration (AMD). However, the limited treatment response prompts further investigations into its molecular effects.<br><br>METHODS: We prospectively collected aqueous humor (AH) samples from 11 patients with GA before and at 2 months during pegcetacoplan treatment. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze the proteome, and global normalization was applied to account for differences in protein concentration. To assess global proteomic shifts over time, principal component analysis (PCA) was performed. The Friedman test was used to assess differences in protein intensities across time points while adjusting for multiple testing using Benjamini-Hochberg false discovery rate (FDR) correction.<br><br>RESULTS: A total of 283 proteins were analyzed. PCA revealed temporal changes in global protein expression profiles, with a significant shift between baseline and month 2 (P = 0.01). The levels of complement components C3 (P = 0.12) and C5 (P = 0.27) remained stable after initiation of treatment, but the levels of C1qB, C1RL, C2, C6, C7, C8, C9, factor D, factor H, and factor I increased significantly (all P < 0.05). Most non-complement proteins showed no significant changes; however, beta-2-glycoprotein 1 (FDR = 0.09), kininogen 1 (FDR < 0.05), and prothrombin (FDR < 0.05) increased significantly, and kallistatin (FDR < 0.05) and plasma serine protease inhibitor (FDR < 0.05) decreased.<br><br>CONCLUSIONS: This exploratory study suggests that pegcetacoplan modulates the AH proteome in GA. Although no changes in the target protein C3 were detected following treatment, significant changes in proteins tightly connected to complement, inflammation, and coagulation were observed. These findings underscore the need for further investigation into the biological and clinical relevance of the observed molecular shifts.},
}
@article {pmid41346473,
year = {2025},
author = {Buscaglia, M and Gouriou, B and Asquoët, Y and Le Goïc, N and Le Grand, F and Hachem, M and Soudant, P},
title = {Production of [13]C-labeled docosahexaenoic acid from heterotrophic marine microorganisms Aurantiochytrium mangrovei and Crypthecodinium cohnii enabling fluxomic applications.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {13},
number = {},
pages = {1690863},
pmid = {41346473},
issn = {2296-4185},
abstract = {Docosahexaenoic acid (DHA, 22:6n-3) is the predominant polyunsaturated fatty acid in the human brain and eyes, playing a crucial role in vision and cognitive development. DHA deficiency has been associated with ocular diseases, such as macular degeneration and glaucoma, as well as neurodegenerative disorders. Since the human body has a limited ability to synthesize DHA from its precursor, alpha-linolenic acid (ALA, 18:3n-3), targeted DHA supplementation is essential for these patients. To investigate DHA metabolism and integration, researchers commonly use stable ([2]H,[13]C) or radioactive ([3]H,[14]C) isotopes, which are expensive and not widely accessible, restricting the scope and duration of studies. This study aimed to develop a sustainable method for biosynthesizing uniformly labeled [13]C-DHA by culturing the heterotrophic protists Aurantiochytrium mangrovei and Crypthecodinium cohnii with [13]C-glucose. The major fatty acids (FA) of A. mangrovei included 16:0, 22:5n-6 (DPA), and DHA, with DHA accounting for 50.5% ± 4.9% of the total FA. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed a[13]C-enrichment of DHA at 96.7% ± 0.4% after the effective High Performance Liquid Chromatography (HPLC) purification. The predominant FA of C. cohnii were 12:0, 14:0, 16:0, and DHA, with DHA representing around 27% of the total FA and exhibiting a[13]C-enrichment of 86.3% ± 1.6%. Based on FA content, A. mangrovei showed a balanced distribution of neutral and polar lipids, with DHA predominantly in the polar fraction (57.8% ± 3.1%), whereas C. cohnii exhibited a predominance of neutral lipids (82.4% ± 0.3%), which contained the majority of its DHA (57.5% ± 1.0%).},
}
@article {pmid41345313,
year = {2025},
author = {Niknahad, A and Zielińska, A and Auffarth, GU and Son, HS and Lee, H and Khoramnia, R and Łabuz, G},
title = {[Emerging technology for retinal function testing: two-photon microperimetry].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41345313},
issn = {2731-7218},
abstract = {The technique of 2‑photon microperimetry is an emerging procedure that combines measurement of retinal sensitivity with retinal imaging and offers substantial improvements compared to conventional microperimetry. Conventional microperimetry relies on 1‑photon linear absorption while 2‑photon microperimetry relies on the simultaneous absorption of two photons, leading to enough energy for photoisomerization of visual pigments and perception of colors, such as green. This 2‑photon absorption process has shown a lower spread of measurements at one retinal location, leading to more reproducible data compared to conventional microperimetry. The current literature also suggests that 2‑photon microperimetry provides more reliable measurements in the presence of lens opacities, a common issue in an aging eye. Furthermore, it has been successfully utilized to assess retinal function in patients with diabetic retinopathy, age-related macular degeneration and glaucomatous neuropathy. These advantages highlight the very promising application in clinical settings. Future adjustments focusing on implementing this technology in the clinical practice could improve outcomes in the early detection and monitoring of retinal diseases.},
}
@article {pmid41344859,
year = {2025},
author = {Schmidt, I and Volkmer, P and Müskens, RPHM and van der Waaij, AM and van Dam, GM and Huiskamp, EA and Nagengast, WB},
title = {Targeted Fluorescence Imaging of Bevacizumab-800CW in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270802},
pmid = {41344859},
issn = {1535-5667},
abstract = {The purpose of this study was to determine the safety and feasibility of fluorescence molecular imaging using a commercially available system and intravenous injection of fluorescently labeled bevacizumab (bevacizumab-800CW) to visualize bevacizumab distribution in patients with neovascular age-related macular degeneration (nAMD)s. Methods: Twelve patients with active nAMD aged 60 y or older, who were either on anti-vascular endothelial growth factor (VEGF) therapy or were anti-VEGF therapy naïve, received an intravenous injection of 4.5 mg (n = 3) or 15 mg (n = 9) of bevacizumab-800CW. This clinical trial was divided into 2 parts. An interim analysis was performed after the inclusion of 3 patients per dose group (study part 1) to determine the more optimal dose. Then 6 additional patients were included with the optimal dose in study part 2. All patients underwent standard clinical imaging, including fundus photography, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. Fluorescence imaging was performed 1 min, 60 min, and 3-4 d after bevacizumab-800CW injection. Results: Bevacizumab-800CW injections were safe and well tolerated. One minute after injection, only the 15-mg group demonstrated a significantly higher contrast-to-noise ratio (median, 6.32) in vessels compared with baseline (median, -4.44; P = 0.0342). This, combined with the clear visual uptake after 3-4 d, supported 15 mg as the preferred dose. Contrast-to-noise ratio values inside the macula of patients receiving 15 mg of bevacizumab-800CW (n = 8) were significantly higher after 3-4 d (median, 4.45) compared with baseline (median, 0.19; P = 0.0078). Conclusion: Targeted fluorescent tracers such as bevacizumab-800CW can visualize VEGF expression, providing important insights into nAMD, and can pave the way toward personalized treatments and targeted drug development.},
}
@article {pmid41343426,
year = {2025},
author = {DeLucia, PR and Oberfeld, D and Kearney, JK and Cloutier, M and Jilla, AM and Zhou, A and Corona, ST and Cormier, J and Taylor, A and Wykoff, CC and Baurès, R},
title = {Visual, auditory, and audiovisual time-to-collision estimation among participants with age-related macular degeneration compared to a normal-vision group: The TTC-AMD study.},
journal = {PloS one},
volume = {20},
number = {12},
pages = {e0337549},
doi = {10.1371/journal.pone.0337549},
pmid = {41343426},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/physiopathology ; Male ; Female ; Aged ; *Visual Perception/physiology ; *Auditory Perception/physiology ; Aged, 80 and over ; Middle Aged ; Cues ; *Vision, Ocular ; },
abstract = {Little is known about whether and to what degree people with different amounts of visual impairment rely on hearing instead of vision for mobility, particularly in judgments of collision. We measured how much importance was assigned to visual and auditory cues during time-to-collision judgments made by people with age-related macular degeneration (Impaired Vision Group; IV) compared to a control group without age-related macular degeneration (Normal Vision Group; NV). A virtual reality system simulated a roadway with an approaching vehicle viewed from the perspective of a pedestrian. Participants pressed a button to indicate the time the vehicle would reach them. The vehicle was presented visually only, aurally only, or both simultaneously. Standardized regression coefficients and general dominance weights indicated that time-to-collision (TTC) judgments were determined by both auditory and visual cues in both groups. In the vision-only modality condition, the relative importance of distance and optical size compared to TTC was higher in the IV group compared to the NV group, but with a relatively small effect size. In all modality conditions, the mean absolute error of TTC estimates was comparable between groups, and a multimodal advantage was not observed. Intraindividual variability was greater in the IV group only in the AV condition. The implication is that similar performance can be achieved through the use of different sources of information. Importantly, people with and without IV achieved similar performance but showed differences in the relative importance of different sensory sources of information. A comparison of two IV subgroups differing in severity suggested that simply having IV in both eyes is not sufficient to predict TTC estimation differences between people with IV and people without IV who have normal vision. Rather it appears to be the degree of bilateral visual impairment of the IV that matters.},
}
@article {pmid41342744,
year = {2025},
author = {Cakici, O and Yilmaz, OF and Karaca, S and Sarmis, A and Mutlu, MA and Sahin, ZB and Borucu, B and Oguz, H},
title = {Conjunctival Microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251393397},
doi = {10.1177/11206721251393397},
pmid = {41342744},
issn = {1724-6016},
abstract = {PurposeThis study aimed to investigate the conjunctival microbiota of patients requiring intravitreal injections due to diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO).MethodsA total of 182 participants (46 DR, 71 AMD, 16 RVO, and 49 controls) were enrolled between August and November 2024. Conjunctival swabs were collected from both eyes under sterile conditions prior to injection and cultured on 5% sheep blood and chocolate agar. Microorganisms were identified using Vitek MS.ResultsNo significant differences were observed among the groups in overall microbial growth frequency (all p > 0.05). Gram-negative bacteria, fungi, and polymicrobial growth were more frequently detected in DR and AMD patients, suggesting a trend toward greater microbial diversity, although these differences were not statistically significant.ConclusionDR and AMD patients exhibited higher prevalence of gram-negative, fungal, and polymicrobial colonization. These findings underscore the importance of strict aseptic preparation, povidone-iodine disinfection, and targeted prophylactic strategies to minimize post-injection infection risk in high-risk populations.},
}
@article {pmid41342623,
year = {2025},
author = {Peter, VG and Hayoz, M and Scandella, D and Sznitman, R and Escher, P and Zinkernagel, MS},
title = {AI-Assisted Optical Coherence Tomography Segmentation for Enhanced Diagnosis of Inherited Retinal Diseases.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {12},
pages = {8},
doi = {10.1167/tvst.14.12.8},
pmid = {41342623},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnosis/diagnostic imaging/genetics ; *Artificial Intelligence ; Male ; Female ; Middle Aged ; Aged ; Algorithms ; Adult ; Macular Degeneration/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Retina/diagnostic imaging ; },
abstract = {PURPOSE: Inherited retinal diseases (IRDs) are rare and diverse, posing a diagnostic challenge in ophthalmology. This study aimed to determine whether artificial intelligence (AI)-assisted image processing can improve IRD diagnosis and provide insights into disease characteristics. We used an optical coherence tomography (OCT) segmentation algorithm to characterize retinal features in IRDs. Two control groups were included to enhance the contextual understanding of these features: healthy eyes and eyes with age-related macular degeneration (AMD). An AI-driven classification model was then used to classify the data into disease and control groups.<br><br>METHODS: We analyzed 327 images from 181 patients with IRD and 146 control individuals, including healthy subjects and patients with AMD. IRD cases were stratified into macular and retinal dystrophies. Automated segmentation of six retinal layers and detection of nine biomarkers were performed on retinal OCT images using the AI-based RetinAI Discovery tool. A random forest classifier differentiated macular IRD, retinal IRD, and controls.<br><br>RESULTS: The model detected IRD with 91% accuracy and achieved 91% accuracy in differentiating macular from retinal IRD. Key OCT features for differentiation included reduced perifoveal photoreceptor and outer nuclear layer thicknesses and increased retinal nerve fiber layer thickness in retinal IRD. Macular IRD featured significant foveal photoreceptor and outer nuclear layer thinning.<br><br>CONCLUSIONS: This study shows that standardized OCT image analysis combined with AI-based classification can accurately detect and stratify IRDs. The model's high accuracy highlights its potential as a reliable diagnostic tool in ophthalmology.<br><br>TRANSLATIONAL RELEVANCE: This AI-assisted OCT evaluation approach enhances ophthalmic diagnostics by improving IRD detection and classification.},
}
@article {pmid41342587,
year = {2025},
author = {Zhao, S and Voegele, F and Tang, J and Clark, SJ and Tschulakow, AV and Julien, S},
title = {Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {23},
pages = {e71307},
doi = {10.1096/fj.202502226R},
pmid = {41342587},
issn = {1530-6860},
support = {//Dr. Werner Jackstaedt Stiftung, Germany/ ; //Guangzhou Elites Scholarship Council, China/ ; //Open access Publishing Fund of University of Tuebingen/ ; },
mesh = {Animals ; *Geographic Atrophy/chemically induced/pathology/metabolism ; *Iodates/toxicity ; Rats ; Disease Models, Animal ; Rats, Long-Evans ; Retinal Pigment Epithelium/pathology/metabolism ; *Inflammation/pathology/metabolism/chemically induced ; Tomography, Optical Coherence ; Electroretinography ; Male ; },
abstract = {Geographic atrophy (GA) is characterized by the loss of choriocapillaris, retinal pigment epithelium (RPE) and photoreceptors and is an advanced form of age-related macular degeneration (AMD)-a leading cause of central vision loss in the elderly. The development of effective treatments has been hindered by the lack of reliable animal models that recapitulate the structural, functional, and molecular hallmarks of GA. In this study, we established and extensively characterized a sodium iodate (NaIO3)-induced model of GA in pigmented Long Evans rats using a comprehensive set of in vivo and histological techniques. NaIO3 was administered intraperitoneally at 80 mg/kg to induce bilateral retinal degeneration. Morphological, functional, and ultrastructural changes were evaluated using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG), light and electron microscopy, and immunohistochemistry at pre-dose and 3, 7, and 14 days post-injection. The model exhibited typical GA features including choriocapillaris loss, RPE degeneration, photoreceptor death, Bruch's membrane remodeling, and mitochondrial damage. Complement activation (C3, C5b-9) and immune cell infiltration (Iba1, CD68) were observed, along with gliosis and RPE65 loss. ERG analysis revealed profound and persistent functional deficits. These findings demonstrate that the NaIO3 rat model robustly mimics the key pathological events in GA, particularly at 7 days post-injection, making it a suitable model for preclinical evaluation of therapeutic interventions targeting choriocapillaris and RPE protection.},
}
@article {pmid41341962,
year = {2025},
author = {Ly, A and Harnick, E and Jowsey, T and Bannatyne, AJ},
title = {Qualitative Factors Impacting Patients and Clinicians Regarding Intravitreal Injections for Retinal Disorders: A Scoping Review.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {4349-4365},
pmid = {41341962},
issn = {1177-5467},
abstract = {BACKGROUND: Intravitreal injections are among the most frequently performed eye procedures worldwide. They are vital in managing vision-related retinal conditions such as neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion. This review scopes qualitative research concerning people's beliefs, perspectives, experiences and behaviors towards intravitreal injections.<br><br>METHODS: Academic databases (PubMed, Embase, CINAHL and Web of Science) were searched for studies focused on qualitative research of intravitreal injections in adult patients, published between January 2000 and May 2024. We extracted data regarding publication and participants' characteristics, main study objectives, and methodological approaches.<br><br>RESULTS: Of the 795 identified citations, 28 met the inclusion criteria. Most studies reported on patients' emotional experiences of undergoing intravitreal injections, with the fear of vision loss compounded with ongoing injections prompting significant anxiety and uncertainty for patients. Other studies also reported on the physical component as the invasiveness of the procedure caused pain and discomfort, which varied with the clinician's delivery of the injection. One study reported on clinician experiences of performing intravitreal injections, stating that the treatment decisions are dependent on patient-related factors such as their adherence to regular injections. Overall, qualitative research in ophthalmology is increasing, with most studies employing semi-structured interviews with thematic analysis.<br><br>CONCLUSION: Qualitative research offers valuable insights into both patient and clinician experiences of intravitreal injections, which can shape person-centered and sustainable models of intravitreal treatment. Understanding qualitative factors such as personal experiences and barriers to treatment can refine the delivery of intravitreal injections and ultimately improve patient adherence.},
}
@article {pmid41340913,
year = {2025},
author = {Sun, M and Wang, J and Fan, W and Wang, K and Wang, Y and Zhang, J and Ding, S and Zhang, C and Feng, Z and Wang, YG and Song, Z and Tao, Y},
title = {From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics.},
journal = {Materials today. Bio},
volume = {35},
number = {},
pages = {102537},
pmid = {41340913},
issn = {2590-0064},
abstract = {Delivering medications to targeted lesions poses significant challenges due to the unique anatomical structure and physical barriers of the eyeball. Polymer nanomicelles are spontaneously assembled from surfactants and amphiphilic polymers, encapsulating insoluble drugs within their cores to augment their hydrosolubility. Nanomicelles have demonstrated potential to surmount these biological hurdles and convey encapsulated therapeutic agents to intended sites. Nanomicelle can prolong the drug half-life and promote molecule permeation through ocular epithelium. Notably, they can be formulated at concentrations marginally exceeding the critical micelle concentration while maintaining a stable conformation, thereby boosting therapeutic effectiveness. Moreover, the physicochemical attributes of polymeric micelles can be precisely adjusted by integrating diverse hydrophilic or hydrophobic moieties. Surface modifications can further impart specific charges or facilitate targeted organ delivery enhancing adhesion to ocular tissues and mitigating systemic toxicity. This review delves into the utilization of polymer nanomicelles in ophthalmological practice, encompassing block copolymer design, the pharmacokinetics of encapsulated drugs within nanomicelles, and the molecule pathways governing nanomedicines. This review also explores their applications in treating ocular disorders including infectious keratitis, DED, glaucoma, corneal graft rejection, neovascular age-related macular degeneration (nAMD), and DR, while introducing progress in clinical deployment and potentials in ocular diagnosis. We also discuss the key challenges in clinical translation and scalable manufacturing. With continued optimization, polymer nanomicelles are poised to become a versatile, non-invasive platform for personalized ophthalmologic therapies.},
}
@article {pmid41337039,
year = {2025},
author = {Abay, SG and Asmare, MH and Geurts, L},
title = {An Affordable Smartphone-based Fundus Imaging Device for Retinal Examination.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-6},
doi = {10.1109/EMBC58623.2025.11254224},
pmid = {41337039},
issn = {2694-0604},
mesh = {*Smartphone ; Humans ; *Fundus Oculi ; *Retina/pathology/diagnostic imaging ; Glaucoma/diagnosis ; Equipment Design ; Optic Disk/pathology ; },
abstract = {Fundus imaging is widely used for diagnosing and monitoring ocular diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration. However, the high cost and limited availability of conventional fundus cameras pose significant barriers, particularly in resource-constrained settings. This study introduces the Glaucoma Screening on Phone (GSoP), an affordable and portable smartphone-based fundus imaging adapter designed to address these challenges. The adapter is developed using accessible and cost-effective components. We recorded retinal videos from dilated pupil with a focus on the optic disc region, which provides critical information on the degeneration of the optic nerve. While field testing revealed artifacts such as glare that reduced overall image quality, the GSoP demonstrated its ability to capture diagnostically relevant images of the optic disc region. A subjective qualitative comparison with the commercially available ophthalmoscope called oDocs-nun showed that although the GSoP's field of view is smaller, it effectively highlights the optic nerve head, a critical area for glaucoma screening. Our approach is well-suited for mydriatic video-based screening due to its limited field of view. With a production cost of under C10, the GSoP offers a practical and accessible solution for primary healthcare and educational purposes. Future improvements, including glare reduction mechanisms, AI-driven automation, and modular design options, have the potential to enhance its diagnostic capabilities and broaden its impact.},
}
@article {pmid41335743,
year = {2025},
author = {Herrero-Tudela, M and Romero-Oraa, R and Hornero, R and Gutierrez-Tobal, GC and Lopez, MI and Romero-Aroca, P and Garcia, M},
title = {Explainable Artificial Intelligence for Early Detection and Diagnosis of Age-Related Macular Degeneration.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-4},
doi = {10.1109/EMBC58623.2025.11254905},
pmid = {41335743},
issn = {2694-0604},
mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Artificial Intelligence ; Early Diagnosis ; Algorithms ; Neural Networks, Computer ; Deep Learning ; Diagnosis, Computer-Assisted/methods ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Early identification of individuals at risk of progressing from an asymptomatic stage to advanced AMD is critical for preventing severe vision loss. Automated image assessment systems for AMD can enhance screening efficiency by reducing time, cost, and effort. Despite the success of convolutional neural networks in AMD detection, their limited interpretability restricts their use in clinical practice. To address this issue, we present an explainable deep-learning approach based on ResNetRS-200, incorporating Kernel SHAP for model interpretability. Our approach achieved a quadratic kappa of 0.6927 and an accuracy of 60.95% on the publicly available Age-Related Eye Disease Study dataset, while achieving a quadratic kappa of 0.7784 and an accuracy of 77.95% on a private dataset. Kernel SHAP analysis highlighted specific retinal regions close to the macula influencing the predictions of the model, providing a clinically interpretable framework, and enhancing diagnostic confidence. Our findings demonstrate the effectiveness of the proposed framework for automated AMD grading. Therefore, the proposed method could be an explainable diagnostic aid for the early detection and grading of AMD.Clinical relevanceThis research establishes the useful- ness of an eXplainable Artificial Intelligence approach using ResNetRS-200 architecture and Kernel SHAP for automated AMD grading.},
}
@article {pmid41335529,
year = {2025},
author = {Machna, B and Jastrzebska-Miazga, I and Pacwa, A and Liu, X and Oseka, M and Smedowski, A},
title = {Experimental models of myopia development: A review of literature.},
journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society},
volume = {76},
number = {4},
pages = {335-367},
doi = {10.26402/jpp.2025.4.01},
pmid = {41335529},
issn = {1899-1505},
mesh = {*Myopia/physiopathology/etiology/epidemiology/pathology ; Humans ; Animals ; *Disease Models, Animal ; Refraction, Ocular ; },
abstract = {Myopia is one of the most prevalent refractive errors and one of the leading causes of visual impairment and blindness worldwide. It results from a mismatch between the axial length and optical power of the eye, resulting in a focal plane that lies in front of the retina. In children and young adults, myopia is most commonly caused by excessive elongation of the eyeball during development - a hallmark of school-age and some early-onset genetic forms of myopia. However, myopic refractive error can also result from other mechanisms, such as increased lens power in age-related nuclear cataracts or corneal steepening in keratoconus, which are not associated with axial elongation. The prevalence of myopia in young Asian adults has increased from 20-30% to 80-85% over the last 50 years. In contrast, recent meta-analytic data for European young adults, emphasizing studies with cycloplegic refraction essential for accuracy, indicate myopia prevalence rates of approximately 19-24%. The prevalence of high myopia (greater than or equal to-6.0 diopters) has increased disproportionately to myopia in the last 50 years, from 1-5% to 10-20% and became a global problem. The reason for this state of affairs is believed to be lifestyle and prolonged near vision activities. Although refractive error can be corrected, sight-threatening pathologies such as retinal detachment, macular degeneration, glaucoma, and cataracts are more challenging to control. Owing to years of research, the biological mechanisms of eye growth and refractive development are increasingly elucidated. The signaling cascade mechanisms that link the retinal image processing and alterations in choroidal thickness and scleral development have also been studied. While the retina can detect defocus and changes in defocus, decades of research have led to a growing understanding of the fundamental pathways in visually guided eye growth, yet the precise initial mechanisms by which the retina senses and transduces these optical signals continue to be an active and important area of investigation. Animal studies have demonstrated that the retina can locally regulate visually guided eye growth through intrinsic mechanisms, even in the absence of direct input from the brain. The precise molecular mechanisms underlying common forms of myopia, particularly those involving axial elongation, are yet to be fully elucidated. This reflects the complexity and multifactorial influences inherent even in these prevalent forms, alongside the challenges posed by experimental models in completely recapitulating all aspects of the human condition.},
}
@article {pmid41335372,
year = {2025},
author = {Shirley, M},
title = {Elamipretide: First Approval.},
journal = {Drugs},
volume = {},
number = {},
pages = {},
pmid = {41335372},
issn = {1179-1950},
abstract = {Elamipretide (Forzinity™) is a mitochondrial cardiolipin binder being developed by Stealth BioTherapeutics for the treatment of a range of disorders featuring mitochondrial dysfunction. In September 2025, elamipretide was granted accelerated approval in the USA for use to improve muscle strength in adult and pediatric patients with Barth syndrome weighing ≥ 30 kg. With this accelerated approval, elamipretide became the first disease-specific treatment approved for Barth syndrome, an ultra-rare X-linked recessive genetic disorder. Elamipretide is also under phase III clinical development for use in the treatment of dry age-related macular degeneration and mitochondrial myopathies. This article summarizes the milestones in the development of elamipretide leading to this first approval for Barth syndrome.},
}
@article {pmid41335185,
year = {2025},
author = {de Angelis, L and Galasso, M and Di Simplicio, S and Raimondi, R and Vidal-Aroca, F and Romano, MR and Toro, MD and Rizzo, S and Barca, F},
title = {Correction: In Vivo Evaluation of SING IMT™ Alignment for Late-Stage Age-Related Macular Degeneration Using Anterior Segment OCT.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40123-025-01294-w},
pmid = {41335185},
issn = {2193-8245},
}
@article {pmid41335184,
year = {2025},
author = {Augustin, AJ and Koss, M},
title = {Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41335184},
issn = {2193-8245},
}
@article {pmid41335183,
year = {2025},
author = {Borrelli, E and Coco, G and Scorcia, V and Carnevali, A and Reibaldi, M and Giannaccare, G},
title = {A Response to: Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41335183},
issn = {2193-8245},
}
@article {pmid41334307,
year = {2025},
author = {Sadeghi, E and Mahmoudinezhad, G and Valsecchi, N and Vupparaboina, SC and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J},
title = {Long-Term Follow-Up of Dry Age-Related Macular Degeneration Patients.},
journal = {Journal of current ophthalmology},
volume = {37},
number = {1},
pages = {78-85},
pmid = {41334307},
issn = {2452-2325},
abstract = {PURPOSE: To assess the progression rate from dry age-related macular degeneration (dAMD) to advanced AMD and possible risk factors.<br><br>METHODS: Demographics, medical and ocular conditions, baseline eye examinations, optical coherence tomography features, and progression rates to advanced AMD were collected.<br><br>RESULTS: We included 74 eyes from 47 dAMD patients, with a mean age of 74.58 &#xb1; 8.29 years and 38.30% males. During a follow-up period of 8.9 &#xb1; 0.4 years, 40 eyes (54.05%) progressed to advanced AMD, with 25 eyes (33.78%) developing neovascular AMD (nAMD) and 22 eyes (29.72%) progressing to geographic atrophy (GA). Patients progressing to advanced AMD were older (77.8 &#xb1; 6.5 vs. 73.8 &#xb1; 9.5, P = 0.03). A higher incidence of open-angle glaucoma (OAG) was noted in progressing eyes (32.5% vs. 8.8%, P = 0.01), along with thinner baseline central macular thickness (CMT) (247.93 &#xb1; 32.55 vs. 268.67 &#xb1; 16.75, P = 0.007). Smokers with OAG had a higher tendency to develop nAMD (P < 0.05). Females with lower best-corrected visual acuity (BCVA) were more likely to develop GA (P < 0.001).<br><br>CONCLUSIONS: The progression rate to advanced AMD was 54.05% over 8.9 &#xb1; 0.4 years. Advanced age, reduced baseline CMT, and lower BCVA were linked to progression. OAG and smoking were associated with higher nAMD, while females had a higher risk of GA.},
}
@article {pmid41334300,
year = {2025},
author = {Sarkar, AD and Kannan, NB and Thakur, S and Balakrishnan, TN and Ramasamy, K},
title = {Long-Term Outcome of Intravitreal Expansile Gas and Bevacizumab Injection for Macular Neovascularization-Induced Subfoveal Hemorrhage: A Retrospective Study.},
journal = {Journal of current ophthalmology},
volume = {37},
number = {1},
pages = {86-92},
pmid = {41334300},
issn = {2452-2325},
abstract = {PURPOSE: To analyze the results of the long-term outcome of pneumatic displacement (PD) with intravitreal bevacizumab (IVB) for subfoveal hemorrhage (SFH) secondary to polypoidal choroidal vasculopathy (PCV)/macular neovascularization secondary to neovascular age-related macular degeneration (n-AMD).<br><br>METHODS: This is a retrospective and interventional study executed in the population of southern part of India who attended a tertiary care ophthalmic hospital over a decade. Patients who presented with a complaint of diminution of vision following SFH secondary to PCV or n-AMD who were treated with PD using sulphur hexafluoride (SF6) along with IVB were included in the study. The patients were followed up for at least 24 months posttreatment. Finally, a dataset of 54 patients was chosen who fulfilled all the criteria and a thorough analysis on their long-term outcome was done.<br><br>RESULTS: The mean age at baseline was 57.55 &#xb1; 13.02 years. Average treatment delay was measured 9.43 &#xb1; 5.22 days. Best-corrected visual acuity (BCVA) on presentation was 1.07 &#xb1; 0.46 in logMAR. The average size of the SFH was measured 4.46 &#xb1; 1.17-disc diameter area. The average long-term follow-up was measured 29.33 &#xb1; 4.53 months. Final BCVA improved to 0.74 &#xb1; 0.62 in logMAR (P < 0.001). Overall improvement in BCVA was significantly better, although only a minority of patients (n = 24, 44.44%) improved BCVA &#x2265; 0.3 in logMAR. Subgroup analysis reveals smaller SFH (&#x2264;2 disc diameter) and presentation earlier than 1 week shows comparatively better visual outcome.<br><br>CONCLUSIONS: The study shows encouraging results on the long-term follow-up with respect to anatomical and visual acuity outcome. This serves as the second largest dataset on PD with IVB for SFH secondary to PCV/n-AMD in ophthalmic literature.},
}
@article {pmid41332270,
year = {2025},
author = {Li, KV and Pan, A and Liu, YV and Antonio-Aguirre, B and Wang, J and Adams, M and McNerney, C and Tun, SBB and Jimenez, K and Lu, Y and Li, Z and McNally, M and Barathi, VA and Johnston, RJ and Singh, MS},
title = {Application of Machine Learning to Discriminate Photoreceptor Cell Species in Xenotransplanted Chimeric Retinas.},
journal = {Clinical and translational science},
volume = {18},
number = {12},
pages = {e70420},
pmid = {41332270},
issn = {1752-8062},
support = {R01EY033103/EY/NEI NIH HHS/United States ; R01EY030872/EY/NEI NIH HHS/United States ; F31EY033187/EY/NEI NIH HHS/United States ; /FFB/Foundation Fighting Blindness/United States ; //Shulsky Foundation/ ; //Joseph Albert Hekimian Fund/ ; G2019300//BrightFocus Foundation/ ; //Maryland Technology Development Corporation/ ; //Juliette RP Vision Foundation/ ; 147042//Knights Templar Eye Foundation/ ; //Wilmer Pooled Professor Fund (PPF) Lutty Grant/ ; EY001765//Johns Hopkins University/ ; },
mesh = {*Machine Learning ; Animals ; Humans ; Mice ; Swine ; *Transplantation, Heterologous/methods ; *Retina/cytology/transplantation ; *Retinal Degeneration/pathology/therapy ; *Photoreceptor Cells, Vertebrate/transplantation ; Disease Models, Animal ; Species Specificity ; Organoids/transplantation/cytology ; Heterografts ; Human Embryonic Stem Cells/transplantation/cytology ; },
abstract = {Photoreceptor transplantation is being studied to restore visual function in retinal diseases causing blindness, including age-related macular degeneration, hereditary eye diseases, and traumatic retinopathy. Preclinical studies often involve delivering exogenous human photoreceptor cells into animal models' retinas. A key readout in such experiments is distinguishing donor cell integration from artificial labeling secondary to material transfer of cytosolic or nuclear labels. Recognizing donor (human) versus animal photoreceptor nuclei is key, but purely immunohistology discrimination is challenging due to antigenic species overlap or intercellular antigen transfer. To address this, we sought to develop and validate a computational technique to discriminate between photoreceptor cells of different animal species based on machine learning of nuclear morphology. We aim to evaluate the feasibility of computer-assisted nuclear detection combined with random forest classification to automate species differentiation in DAPI-stained photoreceptors after xenotransplantation into mouse and pig retinas. Our models were trained on single-species samples and validated with mixed-species samples. We then transplanted human embryonic stem cell-derived retinal organoid cells into rodent and pig retinal degeneration models. The random forest model accurately determined cell identity post-xenotransplantation, validated by histological assessment using an antihuman nuclear antibody. Our results support the potential efficacy of employing machine learning image analysis and classification techniques that may promote experimental rigor, minimize observer bias, and enable high throughput semiautomated workflows for transplantation outcomes analysis. The methodological framework reported here may enable a more nuanced and precise analysis of the behavior of transplanted photoreceptors for the purposes of human retinal regeneration.},
}
@article {pmid41331277,
year = {2025},
author = {Moon, S and Park, S and Kim, CG and Kim, J and Yoon, YS and Kim, JH},
title = {Predicting visual acuity using optical coherence tomography in patients with neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-28738-4},
pmid = {41331277},
issn = {2045-2322},
support = {25ZK1100//Electronics and Telecommunications Research Institute/ ; },
abstract = {This study aimed to assess the feasibility of an artificial intelligence(AI) model to predict visual acuity(VA) using optical coherence tomography(OCT) in treatment-naïve patients with neovascular age-related macular degeneration (AMD). This retrospective study enrolled 240 patients(240 eyes) with pseudophakic neovascular AMD who received antivascular endothelial growth factor therapy. Each patient underwent 10 visits where they underwent best-corrected visual acuity(BCVA) testing and horizontal OCT scans, yielding 2,400 images. The images were cropped, resized to 224 × 224 pixels, and partitioned at the patient level to avoid data leakage. A pretrained VGG16 CNN was modified for five-class VA classification (< 0.1, 0.1-0.3, 0.3-0.5, 0.5-0.8, ≥ 0.8). The performance was assessed by five-fold cross-validation using the macro-averaged AUC, accuracy, Top-2 accuracy, and binary accuracy (threshold VA = 0.5). The average performance showed a macro-averaged AUC of 0.772, accuracy of 50.3%, Top-2 accuracy of 71.0%, and binary accuracy of 79.6%. For high-confidence predictions (29.2% of the samples), the accuracy improved to 74.1%, with a binary accuracy of 94.2%. ROC analyses demonstrated AUCs of 0.73-0.83 across VA categories, with the strongest discrimination for VA < 0.1 (AUC 0.83). The confusion matrix showed that the VA 0.5-0.8 and ≥ 0.8 categories achieved relatively higher accuracies; however, misclassifications mainly occurred between these adjacent ranges, with frequent bidirectional errors observed. Our pretrained VGG16 showed moderate ability at predicting VA from OCT images in patients with neovascular AMD. While the overall classification was limited, high binary accuracy highlights the potential clinical value of distinguishing good from poor vision.},
}
@article {pmid41329005,
year = {2025},
author = {Trinh, M and Duong, A and Cheung, R and Chen, S and Ng, D and Friedrich, J and Hodge, C and Nivison-Smith, L and Ly, A},
title = {Determinants of Intergrader Agreement for Key Retinal Photography and OCT Biomarkers in AMD.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {12},
pages = {4},
doi = {10.1167/tvst.14.12.4},
pmid = {41329005},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Biomarkers ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Photography/methods ; Middle Aged ; Aged, 80 and over ; Retinal Drusen ; *Retina/pathology/diagnostic imaging ; Retinal Pigment Epithelium/pathology ; },
abstract = {PURPOSE: To quantify determinants of intergrader agreement for key retinal photography and optical coherence tomography (OCT) biomarkers in early to intermediate age-related macular degeneration (AMD) and to inform future consensus definitions and grading protocol.<br><br>METHODS: Single eyes from 269 participants with early to intermediate AMD were consecutively sampled. Retinal photographs were evaluated for the presence of large drusen and pigmentary abnormalities. OCT B-scans were graded for reticular pseudodrusen (RPD), outer retinal band abnormality (external limiting membrane [ELM], ellipsoid zone [EZ], and retinal pigment epithelium [RPE]), nascent geographic atrophy (nGA), intraretinal hyperreflective foci (IHRFs), hyporeflective drusen cores (hDCs), shallow irregular RPE elevations (SIREs), and drusenoid pigment epithelial detachment (DPED). Biomarkers were classified using a trinary certainty system: "definitely present" (&#x2265;90%), "questionably present" (50%-90%), or "absent" (<50%). The main outcome was odds of intergrader agreement from generalized estimating equations adjusting for intraparticipant correlations, biomarker type, and eye- and participant-level factors.<br><br>RESULTS: Odds of agreement were comparable for large drusen, nGA, RPE abnormality, IHRF, and ELM abnormality; higher for RPD (odds ratio [95% confidence interval], 3.17 [1.56-6.45], P < 0.01); and lower for SIRE, EZ abnormality, pigmentary abnormalities, hDC, and DPED (up to 0.5 [0.32-0.78], P < 0.01). Agreement improved with higher grading certainty (1.4 [1.22-1.6], P < 0.0001) but declined with age (per decade, 0.8 [0.7-0.93], P < 0.01).<br><br>CONCLUSIONS: Biomarker type, grading certainty, and participant age influence OCT agreement. Consensus definitions and grading protocols, including the use of high certainty thresholds (&#x2265;90%), may improve consistency.<br><br>TRANSLATIONAL RELEVANCE: Implementing consensus definitions and protocols can improve agreement and strengthen the clinical utility of OCT biomarkers in AMD.},
}
@article {pmid41328785,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Wang, YX and Jonas, RA},
title = {Associations of macular drusen in an East Asian population. The Beijing Eye Study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70043},
pmid = {41328785},
issn = {1755-3768},
support = {82271086//National Natural Science Foundation of China/ ; },
abstract = {PURPOSE: To assess associations of macular drusen in a general population, affected by age-related macular degeneration (AMD) or free of any retinal disease.<br><br>METHODS: Participants of the population-based cross-sectional Beijing Eye Study underwent optical coherence tomography. Macular volume scans were assessed for macular drusen.<br><br>RESULTS: The study included 870 eyes (870 participants) (age: 64.7&#x2009;&#xb1;&#x2009;9.9&#x2009;years; range: 50-91&#x2009;years), randomly selected within the groups of early AMD (n&#x2009;=&#x2009;356 (40.9%) eyes), intermediate AMD (n&#x2009;=&#x2009;201; 23.1%), late AMD (n&#x2009;=&#x2009;6; 0.7%) and within eyes without AMD (n&#x2009;=&#x2009;307; 35.3%). In multivariable analysis, higher drusen count was associated (r[2]&#x2009;=&#x2009;25) with older age (beta: 0.08; p&#x2009;=&#x2009;0.048), higher serum concentration of cholesterol (beta: 0.10; p&#x2009;=&#x2009;0.008), shorter axial length (beta: -0.09; p&#x2009;=&#x2009;0.03), thicker subfoveal choroidal thickness (beta: 0.08; p&#x2009;=&#x2009;0.04), higher prevalences of macular hyperpigmentations (beta: 0.13; p&#x2009;<&#x2009;0.001), hyperreflective foci (HRFs) (beta: 0.12; p&#x2009;=&#x2009;0.004) and reticular pseudodrusen (beta: 0.27; p&#x2009;<&#x2009;0.001), and a lower prevalence of a visible Henle's layer (beta: -0.15; p&#x2009;<&#x2009;0.001). Larger drusen size was associated with shorter axial length (beta: -0.08; p&#x2009;=&#x2009;0.03), thicker subfoveal choroidal thickness (beta: 0.18; p&#x2009;<&#x2009;0.001), higher prevalences of macular hypopigmentations (beta: 0.14; p&#x2009;<&#x2009;0.001) and HRFs (beta: 0.31; p&#x2009;<&#x2009;0.001), and lower prevalences of a visible Henle's layer (beta: -0.19; p&#x2009;<&#x2009;0.001) and of reticular pseudodrusen (beta: -0.09; p&#x2009;=&#x2009;0.02).<br><br>CONCLUSIONS: In this population-based study on Chinese, higher macular drusen count was associated with shorter axial length, thicker subfoveal choroidal thickness, higher prevalences of macular hyperpigmentations, HRFs and reticular pseudodrusen and lower prevalence of a visible Henle's layer. These findings may be clinically helpful and etiologically interesting.},
}
@article {pmid41328469,
year = {2025},
author = {Ermilov, VV and Nesterova, AA},
title = {[Amyloidogenesis and neurotrophic dysfunction in age-related macular degeneration in correlation with Alzheimer's disease].},
journal = {Arkhiv patologii},
volume = {87},
number = {6},
pages = {61-68},
doi = {10.17116/patol20258706161},
pmid = {41328469},
issn = {0004-1955},
mesh = {Humans ; *Alzheimer Disease/pathology/metabolism/genetics/complications ; *Macular Degeneration/pathology/metabolism/genetics/complications ; *Amyloidosis/pathology/metabolism/genetics ; *Amyloid/metabolism/genetics ; Aged ; Glaucoma, Open-Angle/pathology/metabolism/genetics ; },
abstract = {The pathogenesis of diseases associated with amyloid deposition in various organs and tissues has been a concern for researchers and clinicians since their discovery. Particular attention is paid to the relationship between amyloidogenesis and neurotrophic disorders in age-related neurodegenerative pathology. In this context, the amyloid cascade theory and the neurotrophic dysfunction theory remain relevant, as evidenced by the results of numerous studies conducted in recent years. Meanwhile, it has been shown that amyloidosis, being a systemic pathological process, affects ocular tissues and extraocular structures in various forms with diverse clinical and morphological manifestations. This highlights the need for improved diagnostics of ocular amyloidosis and the study of its association with geriatric ophthalmic diseases such as age-related macular degeneration (AMD), senile cataract, primary open-angle glaucoma, and pseudoexfoliation syndrome. Accumulating evidence suggests that both amyloidogenesis and neurotrophic disturbances share common triggers and mutually contribute to the development of neurodegenerative pathology in both AMD and Alzheimer's disease (AD). Therapeutic strategies aimed not only at suppressing amyloidogenesis and correcting neurotrophic dysfunction but also at the overall regulation of these two pathogenic mechanisms may have a positive effect on geriatric ophthalmic diseases and AD, significantly improving the quality of life of elderly patients. This article summarizes current concepts on the role of neurotrophic dysfunction and amyloidogenic processes in the development of AMD.},
}
@article {pmid41327637,
year = {2025},
author = {Jian, L and Huang, Z and Qi, J and Meng, J and Zhang, K and Zhu, X},
title = {Associations between estimated glucose disposal rate and age-related ocular diseases in cardiovascular-kidney-metabolic syndrome stages 0-3: a large prospective cohort study.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {41327637},
issn = {2397-3269},
mesh = {Humans ; Prospective Studies ; Female ; Male ; *Metabolic Syndrome/complications/metabolism ; Middle Aged ; *Eye Diseases/epidemiology/etiology/metabolism ; Aged ; Risk Factors ; *Blood Glucose/metabolism ; *Cardiovascular Diseases/complications/metabolism ; Incidence ; United Kingdom/epidemiology ; Follow-Up Studies ; },
abstract = {OBJECTIVE: This study investigated the relationship between estimated glucose disposal rate (eGDR) and the risk of age-related ocular diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR) and retinal detachment (RD), in individuals with stages 0-3 of cardiovascular-kidney-metabolic (CKM) syndrome.<br><br>METHODS AND ANALYSIS: This prospective cohort study included 223&#x2009;120 participants from the UK Biobank. The CKM stages were defined based on adiposity, metabolic risk factors and subclinical cardiovascular disease. Lower eGDR values indicate greater insulin resistance. Outcomes were incidences of macular degeneration, glaucoma, cataract, DR and RD. HRs and 95% CIs were estimated using Cox proportional hazards models. Non-linear relationships were explored using restricted cubic splines.<br><br>RESULTS: The study showed that macular degeneration (HR 0.92, 95%&#x2009;CI 0.87 to 0.97, p=0.001) and glaucoma (HR 0.91, 95%&#x2009;CI 0.87 to 0.95, p<0.001) were linearly associated with eGDR. Cataracts exhibited a U-shaped association with eGDR (P non-linear=0.001) and DR exhibited an L-shaped association (P non-linear=0.018). Quartile stratification of eGDR significantly differentiated risk in DR (Q4 vs Q1: HR 0.15, 95%&#x2009;CI 0.04 to 0.52, p=0.003) and RD (Q4 vs Q1: HR 0.65, 95%&#x2009;CI 0.47 to 0.89, p=0.007). Stratified effects analysis revealed that these associations were more significant in advanced CKM syndrome stages.<br><br>CONCLUSIONS: eGDR is associated with ocular diseases risk in CKM syndrome, especially in advanced stages. This finding suggests the potential use of eGDR for guiding ophthalmic screening in CKM management.},
}
@article {pmid41326361,
year = {2025},
author = {Sarkar, S and Kannan, R and Panigrahi, T and Veeramani, K and Mb, T and Shanker Bhattacharya, S and Ghosh, A},
title = {Comparative transcriptomic analysis of retinal response to diverse cellular stresses reveals relative contributions of different cell death processes and signalling networks.},
journal = {Cell death &amp; disease},
volume = {16},
number = {1},
pages = {876},
pmid = {41326361},
issn = {2041-4889},
support = {IA/TSG/20/1/600029//DBT India Alliance (Wellcome Trust/DBT India Alliance)/ ; },
mesh = {Animals ; Oxidative Stress/genetics ; *Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; Cell Death/genetics ; *Signal Transduction/genetics ; Endoplasmic Reticulum Stress/genetics ; *Retina/metabolism/pathology ; *Transcriptome ; Retinal Pigment Epithelium/metabolism/pathology ; Apoptosis/genetics ; *Retinal Degeneration/genetics/pathology/metabolism ; },
abstract = {Retinal degeneration comprises a diverse group of progressive disorders leading to visual impairment and ultimately blindness. These include inherited retinal dystrophies (IRDs), diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma, affecting millions worldwide. The underlying pathology involves dysfunction and death of photoreceptor cells and the retinal pigment epithelium (RPE), driven by various stress-induced cell death mechanisms. Although multiple pathways have been reported, the relative contribution of each remains incompletely understood, highlighting the need for further investigation. Therefore, we studied how different stress types that induce retinal degeneration alter the global gene expression profile in vivo (C57BL/6 mice), aiming to identify predominant cell death mechanisms as well as key genes and networks. Retinal toxicity was induced using established models of oxidative stress, hypoxia, endoplasmic reticulum (ER) stress, and chronic inflammation. Transcriptomic profiling revealed both unique and convergent gene expression changes associated with each stressor. In total, 170, 328, 146, and 151 genes were significantly altered under oxidative stress, inflammation, ER stress, and hypoxia, respectively (Log2 fold change >2 or <-2; p < 0.05). Genes such as Arhgap26, Ccdc9, Ube2e2, and Fndc3b were commonly dysregulated across ER stress, inflammation, and oxidative stress, whereas Nfix, Elp6, Naca, and Plcd3 were selectively altered in oxidative stress, inflammation, ER stress, and hypoxia, respectively. Analysis of cell death-related gene subsets revealed that pyroptosis was commonly activated across different stress types. Additionally, autophagy-mediated cell death, ferroptosis, and extrinsic apoptosis were preferentially associated with oxidative stress, chronic inflammation, and hypoxia, respectively. Both ER and oxidative stress models showed strong activation of autophagy-associated cell death. Together, these findings delineate distinct molecular signatures and predominant cell death mechanisms triggered by specific stressors, providing important insights that could aid in developing targeted therapies to prevent or slow retinal degeneration.},
}
@article {pmid41325920,
year = {2025},
author = {Wang, Z and Zhang, Q and Li, B and Chen, J and Yoshida, S and Sun, B and Zhou, Y},
title = {tRNA-derived small RNAs-Biogenesis, functions, and potential applications in ocular diseases: A review.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {149334},
doi = {10.1016/j.ijbiomac.2025.149334},
pmid = {41325920},
issn = {1879-0003},
abstract = {tRNA-derived small RNAs (tsRNAs), a burgeoning class of small non-coding RNAs, are emerging as pivotal macromolecular regulators in gene expression and cellular signaling networks. Derived from specific cleavage of precursor or mature tRNAs, these molecules exhibit diverse functionalities, including epigenetic remodeling, transcriptional regulation, and translational modulation. Growing evidence underscores their significant roles in the pathogenesis of various ocular diseases, such as age-related macular degeneration, diabetic retinopathy, myopia, and cataract, where they influence critical processes like angiogenesis, inflammation, and neuronal homeostasis. Their dynamic expression profiles in ocular tissues and biofluids position tsRNAs as promising diagnostic biomarkers and therapeutic targets. This review systematically delineates the biogenesis and classification of tsRNAs, elaborates their multifaceted molecular mechanisms, and comprehensively examines their implications in ocular diseases. We further discuss the translational potential of tsRNAs in early detection and precision treatment of ocular diseases, while highlighting current challenges and future directions in this rapidly evolving field.},
}
@article {pmid41324896,
year = {2025},
author = {Kojima, H and Yamashita, A and Nakano, Y and Booka, A and Tatara, Y and Yamada, T and Akimitsu, J and Miyoshi, Y and Osaka, R and Suzuma, K},
title = {Significant Correlation Between Choroidal Thickness and Decrease in Choroidal Blood Flow After Switching to Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41324896},
issn = {2193-8245},
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) therapy suppresses neovascularization in neovascular age-related macular degeneration (nAMD) but may reduce ocular blood flow. However, its relationship with choroidal thickness remains unclear. This study evaluated 1-month outcomes after switching from intravitreal aflibercept or ranibizumab to intravitreal brolucizumab (IVBr) in patients with refractory nAMD.<br><br>METHODS: This prospective, single-center study included 50 eyes of 50 patients with nAMD. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), choroidal stromal area (SA), choroidal luminal area (LA), optic nerve head (ONH) mean blur rate (MBR), and choroidal (CHOR) MBR were evaluated before and 1&#xa0;month after switching to IVBr, with blood flow measured using laser speckle flowgraphy. Univariate analyses were performed to identify potential predictors of changes in CHOR-MBR, and variables with P&#x2009;<&#x2009;0.1 were entered into a multiple regression model.<br><br>RESULTS: BCVA was maintained. CRT decreased from 371.6&#x2009;&#xb1;&#x2009;118.7 to 288.8&#x2009;&#xb1;&#x2009;89.7&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.001). SFCT decreased from 231.9&#x2009;&#xb1;&#x2009;118.7 to 196.0&#x2009;&#xb1;&#x2009;117.4&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.001). CVI showed no significant changes, while SA and LA exhibited significant reductions. ONH-MBR and CHOR-MBR decreased (P&#x2009;=&#x2009;0.004 and P&#x2009;<&#x2009;0.001, respectively). The baseline SFCT was the only significant predictor of change in CHOR-MBR. Older age correlated with thinner baseline SFCT and a greater decrease in CHOR-MBR.<br><br>CONCLUSIONS: IVBr is associated with significant reductions in CRT and SFCT and may decrease choroidal blood flow, particularly in older patients and those with thinner SFCTs.<br><br>TRIAL REGISTRATION: UMIN-CTR Registration ID, UMIN000041382.},
}
@article {pmid41323371,
year = {2025},
author = {Iwama, Y and Masuda, T and Maeyama, A and Eade, KT and Friedlander, M and Nishida, K and Mandai, M},
title = {Cell-based regenerative therapy for retinal diseases: challenges and emerging bioengineering strategies.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {1101-1112},
pmid = {41323371},
issn = {2352-3204},
abstract = {Cell-based regenerative therapy holds promise for a broad spectrum of retinal diseases characterized by irreversible photoreceptor cell (PRC) loss, including retinitis pigmentosa (RP) and age-related macular degeneration. While gene therapy has delivered landmark successes for selected indications, it does not directly replace lost PRCs and is not well suited for advanced-stages of diseases. In this context, cell-based regenerative approaches-either PRC suspensions or retinal sheets-aim to rebuild the outer retinal circuitry and restore light responses across different retinal diseases. In addition to its relatively high prevalence (1 in 3000-5000 individuals), the PRC-specific degeneration pattern in RP has motivated numerous preclinical studies aimed at clinical application. In this review, we first outline the two major graft modalities-cell suspensions and retinal sheet transplantation-from the perspective of their respective advantages and limitations. Here, we summarize preclinical and clinical evidence for both modalities, highlighting the first-in-human trial of transplantation of human iPSC-derived retinal organoid sheets in late-stage RP, which demonstrated a favorable safety profile and two-year graft survival. We then analyze the challenges that emerged from this first-in-human trial and discuss potential bioengineering and biological solutions. Finally, we consider the prospects of extending these transplantation strategies beyond RP to macular diseases, where PRC replacement may also provide therapeutic benefit. Collectively, the field is transitioning from proof-of-concept to diversified clinical exploration; converging advances in developmental biology, genome engineering, and high-throughput cell analytics are poised to accelerate functional vision restoration in retinal diseases.},
}
@article {pmid41321555,
year = {2025},
author = {Gregori, G and Mangoni, L and Muzi, A and Mariotti, C and Lupidi, M},
title = {Neovascular Maculopathy after Laser Retinal Rejuvenation Therapy in a Young Myopic Patient: A Case Report.},
journal = {Case reports in ophthalmology},
volume = {16},
number = {1},
pages = {841-846},
pmid = {41321555},
issn = {1663-2699},
abstract = {INTRODUCTION: Laser photobiomodulation, including retinal rejuvenation therapy (2RT), is a system which selectively targets the retinal pigment epithelium by a concise 3 ns pulse duration. The advantage of this laser system over the traditional thermal laser is that the pulsed, very short duration laser effects can be titrated as spatially confined photodisruptors without resultant conductive thermal spread and therefore collateral damage. It has been investigated primarily in age-related macular degeneration (AMD), particularly in decreasing drusen and slowing the rate of AMD progression. In this case, we have described a case of neovascular maculopathy occurring shortly after 2RT in a young myopic patient.<br><br>CASE PRESENTATION: We report the case of a 28-year-old male who presented with unilateral visual impairment following laser 2RT. Two months before, he was subjected to photorefractive keratectomy for moderate myopia (-3.00 D). The baseline optical coherence tomography (OCT) imaging revealed "sharp-peaked" pigment epithelium detachment (PED) in the subfoveal area. Fluorescein angiography indicated a focal area of irregular foveal hyperfluorescence. Observation was advised, and laser 2RT was performed. However, 1 month later, the patient developed a neovascular lesion in the same eye, confirmed by OCT-angiography, requiring urgent intravitreal anti-VEGF therapy.<br><br>CONCLUSIONS: In summary, this case illustrates a progressive maculopathy culminating in choroidal neovascularization triggered by laser 2RT in a young myopic patient.},
}
@article {pmid41318054,
year = {2025},
author = {Zhang, Z and Shan, X and Liang, F and Fang, L},
title = {Integrative single-cell transcriptomic and experimental analyses unveil Qihuang granule's protection against retinal photodamage via PI3K/AKT/mTOR-mediated autophagy.},
journal = {The international journal of biochemistry &amp; cell biology},
volume = {190},
number = {},
pages = {106881},
doi = {10.1016/j.biocel.2025.106881},
pmid = {41318054},
issn = {1878-5875},
abstract = {Light-induced retinal damage is a significant contributor to age-related macular degeneration (AMD). Qihuang granule (QHG), a traditional Chinese herbal formulation, has been clinically employed in the treatment of retinal diseases, including AMD; however, the precise protective mechanisms remain unclear. This study investigated the protective effects and underlying mechanisms of QHG using a rat model of blue light-induced retinal injury and a human retinal pigment epithelial (ARPE-19) cell model. The results demonstrated that QHG significantly alleviated retinal morphological abnormalities, ultrastructural damage, and apoptosis induced by light exposure. Single-cell RNA sequencing further revealed that specific cell clusters were notably enriched in the PI3K-AKT-mTOR and autophagy-related signaling pathways after QHG treatment, characterized by increased MAP1LC3B (LC3B) expression and decreased SQSTM1 (P62) expression. Validation at the protein and gene levels in vivo confirmed that QHG activated the autophagy pathway by downregulating PI3K, AKT, mTOR, and P62 expression while upregulating LC3B expression. Collectively, this study demonstrates that QHG protects against retinal photodamage by modulating autophagy via the PI3K/AKT/mTOR signaling pathway, providing theoretical support for its clinical application in the treatment of AMD.},
}
@article {pmid41317829,
year = {2025},
author = {Kerwin, AF and Perlman, EM and Browning, DJ},
title = {Atrophy Advisor: A Clinical Tool for Dry Macular Degeneration with Geographic Atrophy.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2025.11.037},
pmid = {41317829},
issn = {1879-1891},
abstract = {OBJECTIVE: To develop and evaluate Atrophy Advisor, a clinical decision tool integrating geographic atrophy (GA) progression and personalized lifespan estimates to help clinicians considering complement factor inhibitor injections for dry macular degeneration with GA.<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: Fifty consecutive patients with GA secondary to nonexudative age-related macular degeneration, seen at Wake Forest-affiliated retina clinics from May 2013 to June 2025.<br><br>METHODS: Fundus images at two or more timepoints were analyzed using ImageJ to measure the distance from the fovea to the nearest GA edge. Pixel-to-micron conversion was made using an assumed vertical disk diameter of 1800 microns. Demographics, comorbidities, and corrected visual acuities were extracted from records. Lifespan estimates were calculated using University of Connecticut (UCONN) and Social Security Administration (SSA) algorithms and compared to observed outcomes.<br><br>MAIN OUTCOME MEASURES: GA edge-to-fovea distance, GA progression rate, corrected visual acuity, and predicted versus observed lifespan.<br><br>RESULTS: Median age was 78 years (IQR: 73.8-82.3); 64% were female. Baseline median GA-to-fovea distance was 792 &#xb5;m (IQR: 509-1213 &#xb5;m), declining to 395 &#xb5;m (IQR: 194-702 &#xb5;m) at last follow-up. Median GA progression was 122 &#xb5;m/year (range 2-627 &#xb5;m/year), with a direct relationship between initial distance and progression rate (p=0.006, R&#xb2;=0.146). Lifespan calculators (UCONN and Atrophy Advisor) yielded median estimates of 11.9 and 11 years, respectively, influencing treatment guidance in 4% of cases.<br><br>CONCLUSIONS: Atrophy Advisor is feasible for combining GA progression kinetics and lifespan estimates to inform treatment decisions. Variability in progression rates and lifespan predictions highlights the need for personalized approaches. Limitations include measurement variability and retrospective design; future studies should validate the tool in larger, prospective cohorts.},
}
@article {pmid41317302,
year = {2025},
author = {Hashimoto, Y and Arai, Y and Takahashi, H and Tampo, H and Kondo, R and Takahashi, H and Yoshida, H and Takahashi, R and Inoda, S and Kaburaki, T and Yanagi, Y},
title = {Increased aqueous flare after intravitreal brolucizumab injections compared to aflibercept in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41317302},
issn = {1435-702X},
support = {21K09751//Japan Society for the Promotion of Science/ ; },
abstract = {PURPOSE: To evaluate aqueous flare values in patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor (VEGF) therapy, including brolucizumab.<br><br>METHODS: This retrospective study included 101 patients treated with intravitreal anti-VEGF injections at Jichi Medical University Hospital from March to July 2021. Aqueous flare values were measured in both affected and fellow eyes. The number of treated eyes was 28 for aflibercept and 73 for brolucizumab. Flare values were compared between affected and fellow eyes, and associations with age, gender, drug type, number of injections, disease duration, and time since last injection were analyzed. We also measured flare values from pre-filled syringes.<br><br>RESULTS: In unilateral treatment cases, brolucizumab-treated eyes had significantly higher aqueous flare values than fellow eyes (6.7 vs. 6.2 photon counts/ms, P&#x2009;=&#x2009;0.0032), while no significant difference was observed with aflibercept (6.9 vs. 6.7 pc/ms, P&#x2009;=&#x2009;0.55). Flare values increased significantly with age in the brolucizumab group (P&#x2009;=&#x2009;0.0076) but not in the aflibercept group (P&#x2009;=&#x2009;0.56). The number of brolucizumab injections did not alter flare values. Multivariate analysis identified age as the only significant factor associated with increased aqueous flare. The mean (standard deviation) flare values measured from pre-filled syringes were 430 (15.6) pc/ms for Beovu[&#xae;] (brolucizumab) and 161.8 (31) pc/ms for Eylea[&#xae;] (aflibercept).<br><br>CONCLUSION: In nAMD, aqueous flare values were higher in brolucizumab-treated eyes and increased with age but were unaffected by the number of injections. Different flare values of each drug might affect the aqueous flare values within hours after injection.},
}
@article {pmid41316464,
year = {2025},
author = {Zhang, Z and Yang, H and Tan, L and Li, Y and Ren, X and Li, X},
title = {Associations between the monocyte‑lymphocyte ratio and age‑related macular degeneration among US adults: evidence from NHANES 2005-2008.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00766-2},
pmid = {41316464},
issn = {2056-9920},
support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; },
abstract = {BACKGROUND: Previous studies have established an association between age-related macular degeneration (AMD) and chronic systemic inflammation. However, the relationship between AMD and the monocyte-to-lymphocyte ratio (MLR), a novel inflammatory biomarker, remains unclear. In this study, we aimed to investigate the association between MLR and AMD using data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).<br><br>METHODS: Data from three NHANES cycles (2005-2008) were analyzed to preliminarily assess the association between MLR and AMD, excluding participants with incomplete data. We utilized weighted logistic regression models, restricted cubic spline functions (RCS) and constructed receiver operating characteristic (ROC) curves to evaluate the association between MLR and AMD.<br><br>RESULTS: A total of 4,894 participants were deemed eligible for our analysis, with 379 individuals diagnosed with AMD. The Monocyte to Lymphocyte Ratio (MLR) was significantly elevated in the AMD group compared to the non-AMD group. After adjusting for potential confounding factors, we found that elevated MLR levels were significantly associated with an increased risk of AMD, with an OR of 2.56, 95% CI: (1.17,5.58), P&#x2009;=&#x2009;0.022. The restricted cubic spline (RCS) analysis revealed a significant nonlinear relationship between MLR and AMD, with an inflection point at 0.26 (nonlinear P&#x2009;<&#x2009;0.05). Furthermore, the receiver operating characteristic (ROC) curve analysis demonstrated that MLR exhibited acceptable discrimination for AMD.<br><br>CONCLUSIONS: Elevated MLR is associated with an increased risk of AMD, suggesting that MLR may serve as a simple and effective clinical biomarker of AMD.},
}
@article {pmid41316395,
year = {2025},
author = {Dundar, A and Cetik Yildiz, S},
title = {Kynurenine pathway metabolites as potential biomarkers in age-related macular degeneration: an ELISA-based prospective study.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {131},
pmid = {41316395},
issn = {2056-9920},
abstract = {OBJECTIVES: Age-related macular degeneration (AMD), in which oxidative stress, inflammation and metabolic imbalances play a role in its pathogenesis, is one of the leading causes of irreversible vision loss. The kynurenine (KYN) pathway, one of the principal routes of tryptophan (TRP) metabolism, constitutes an important mechanism in retinal neurodegeneration. Based on this information, our study aimed to compare the serum TRP, KYN, kynurenic acid (KYNA), 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HAA) and, quinolinic acid (QA) levels of AMD patients and to investigate the diagnostic values of these biomarkers.<br><br>METHODS: Serum samples were collected from AMD patients and control groups. TRP, KYN, KYNA, 3HK, 3HAA, and QA levels were measured using a commercial ELISA method. KYN pathway activity, KYN/TRP and, KYNA/3HK ratios were also assessed. Mann-Whitney U test, ROC analysis, Spearman correlation were applied for statistical comparisons.<br><br>RESULTS: According to our results, 3HK was significantly higher in the AMD group, while TRP, KYN, QA, and KYNA/3HK ratio were higher in the control. ROC analysis revealed 3HK to be the strongest discriminatory marker. The KYNA/3HK ratio also provided significant diagnostic value. Correlation analysis revealed strong negative correlations between 3HK and KYN, QA, and especially KYNA/3HK. Conversely, strong positive correlations were found between KYN and KYNA/3HK, and between TRP, KYN, QA, and KYNA.<br><br>CONCLUSION: KYN pathway metabolites exhibit significant alterations in patients with AMD. 3HK levels and the reduction of the KYNA/3HK ratio suggest a disruption of the neurotoxic-neuroprotective balance and imply that KYN pathway dysfunction may play a role in the pathogenesis of AMD. Among the biomarkers examined, 3HK displayed the highest diagnostic performance, while the KYNA/3HK ratio emerged as an additional biological indicator. These findings indicate that 3HK and the KYNA/3HK ratio may serve as potential biomarker candidates for the early diagnosis and monitoring of AMD.},
}
@article {pmid41316066,
year = {2025},
author = {Pei, Y and Meng, J and He, W and Zhang, K and Guo, D and Lu, Y and Zhu, X},
title = {Unique liver function in high myopia: associations with myopic macular degeneration.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {677},
pmid = {41316066},
issn = {1471-2415},
support = {82301188//National Natural Science Foundation of China/ ; 82122017//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; Middle Aged ; *Myopia, Degenerative/physiopathology/blood/complications ; *Macular Degeneration/blood/physiopathology/etiology ; Adult ; Liver Function Tests ; *Liver/physiopathology ; ROC Curve ; gamma-Glutamyltransferase/blood ; Lipids/blood ; },
abstract = {PURPOSE: To investigate liver function and lipid indexes in patients with high myopia and their association with myopic macular degeneration (MMD).<br><br>METHODS: This cross-sectional comparative study included 995 emmetropic patients and 805 highly myopic patients. Serum levels of liver function and lipid indexes were measured using a Roche C702 biochemical analyzer. Ultra-widefield fundus photographs of eyes were classified according to the International META-PM Classification: Category 0: No myopic retinal degeneration, Category 1: tessellated fundus, Category 2: diffuse choroidal retinal atrophy, Category 3: patchy choroidal retinal atrophy, Category 4: macular atrophy. A machine learning model based on liver function indexes was employed to predict the presence of MMD in patients with high myopia.<br><br>RESULTS: Serum levels of albumin (Alb), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) and triglyceride (TG) were significantly lower, whereas high-density lipoprotein cholesterol (HDL) and apolipoprotein-A (Apo-A) were higher in patients with high myopia than those in emmetropic patients (all P&#x2009;<&#x2009;0.05). Significant differences in serum ALT and GGT were found among MMD categories (both P&#x2009;<&#x2009;0.05). Multivariate logistic regression showed that MMD4 was associated with lower serum GGT than MMD1 (P&#x2009;<&#x2009;0.05). The decision tree model to predict MMD achieved an area under the curve (AUC) of 0.735 using serum GGT (sensitivity&#x2009;=&#x2009;53.12%; specificity&#x2009;=&#x2009;82.09%; P&#x2009;<&#x2009;0.001). When using multiple liver function indexes, the AUC of the model reached 0.803 (sensitivity&#x2009;=&#x2009;73.4%; specificity&#x2009;=&#x2009;76.1%; P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: We identified close associations between liver function and MMD, suggesting serum GGT serve as a potential diagnostic indicator for MMD among highly myopic patients.},
}
@article {pmid41314477,
year = {2025},
author = {Poirot, M and Buñay, J and Ayadi, S and Silvente-Poirot, S and de Medina, P},
title = {Liver X receptors and the hallmarks of aging: From molecular mechanisms to therapeutic opportunities.},
journal = {Ageing research reviews},
volume = {114},
number = {},
pages = {102967},
doi = {10.1016/j.arr.2025.102967},
pmid = {41314477},
issn = {1872-9649},
abstract = {Aging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and other chronic disorders. Therefore, targeting the hallmarks of aging has emerged as a promising strategy to extend healthspan. Liver X receptors (LXRs) are ligand-dependent nuclear receptors that are activated by specific oxysterols and cholesterol derivatives. They are traditionally known as key regulators of cholesterol homeostasis. However, recent evidence reveals that LXRs also influence autophagy, mitochondrial function, epigenetics, senescence, stem cell dynamics, and intercellular communication. This positions LXRs at the crossroads of multiple hallmarks of aging. This review synthesizes current knowledge on endogenous and synthetic LXR ligands, their transcriptional mechanisms, and their effects on the aforementioned hallmarks and age-related pathophysiology. The clinical development of pan-LXR agonists for atherosclerosis has been hindered by side effects, notably hepatic steatosis. Emerging strategies, including LXRβ-selective ligands, selective LXR modulators (SLiMs), and biased agonists such as dendrogenin A, offer ways to separate the protective vascular, metabolic, and neuroprotective effects from adverse outcomes. Additionally, we explore how LXR signaling intersects with the hallmarks of aging and how it can be leveraged to intervene in atherosclerosis, diabetes, cancer, osteoporosis, age-related macular degeneration, and neurodegenerative diseases. Positioning LXRs within the geroscience framework suggests that LXRs may serve as pharmacological hubs to delay aging and its comorbidities. Future work should prioritize isoform- and tissue-selective approaches, metabolite-inspired ligand design, and integration with the hallmarks of aging to unlock the full therapeutic potential of LXRs.},
}
@article {pmid41313467,
year = {2025},
author = {Cheng, X and Lohmann, T and Johnen, S and Walter, P and Baumgarten, S},
title = {Relationship between monocyte-to-lymphocyte ratio and age-related macular degeneration: Findings from a national cross-sectional study.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251402991},
doi = {10.1177/11206721251402991},
pmid = {41313467},
issn = {1724-6016},
abstract = {BackgroundRecent advances have revealed the important role of the immune system in the progression of age-related macular degeneration (AMD). Monocyte-to-lymphocyte ratio (MLR) is a combined marker reflecting inflammation status. However, research on the correlation between MLR and AMD is limited.MethodsIn this cross-sectional analysis, weighted multivariable logistic regression, multinomial logistic regression, subgroup analysis, smoothed curve fitting and threshold effect analysis were used to investigate the relationship between MLR and AMD based on data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).ResultsThis study included data of 4,655 participants. The proportions of no AMD, early AMD and late AMD were 92.27%, 6.79% and 0.95%, respectively. After adjusting for covariates, weighted multivariable logistic regression analysis revealed that MLR was positively associated with AMD (OR = 3.22, 95%CI 1.32-7.82). Threshold effect analysis revealed that higher MLR associated with prevalence of AMD after MLR was greater than 0.37 (OR = 8.93, 95%CI 2.53-31.60). The diagnostic performance of MLR > 0.37 for AMD was assessed using ROC curve analysis. In addition, MLR was proven to have a significant positive correlation with early AMD (OR = 1.20, 95%CI 1.19-1.21) and late AMD (OR = 9.21, 95%CI 9.10-9.31) through weighted multinomial logistic regression.ConclusionsOur study demonstrates that an elevated MLR is independently associated with the prevalence of AMD.},
}
@article {pmid41312773,
year = {2025},
author = {Ju, X and Ramke, J and Turnbull, PR},
title = {Emerging research on non-neovascular age-related macular degeneration treatments.},
journal = {Clinical &amp; experimental optometry},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/08164622.2025.2579872},
pmid = {41312773},
issn = {1444-0938},
abstract = {Age-related macular degeneration (AMD) is a common condition that causes vision impairment in the elderly, significantly impacting their physical and psychosocial well-being. Historically, treatment options to slow or prevent atrophic AMD progression have been limited but are recently increasing in number. This scoping review aims to provide an overview of the research (both preclinical and clinical) on non-neovascular AMD (including early, intermediate, and geographic atrophy) treatments published in the past decade. Our study protocol was prospectively registered on the Open Science Framework.Searches were conducted on MEDLINE, Embase, ProQuest, and CINAHL for studies investigating treatments for atrophic AMD (including early, intermediate, and geographic atrophy stages) published between 1 January 2014 and 14 July 2024, the search date. Data screening, full-text review, and extraction were independently performed by two researchers. Study characteristics and outcomes were summarised, and the results were synthesised narratively. The search identified 1,211 studies, of which 132 were included in this review. Studies were most often conducted in the United States (n = 92, 68.7%) or Europe (n = 25, 18.5%) and most frequently investigated antioxidant or anti-inflammatory treatments (n = 30, 22.7%) or complement pathway inhibitors (n = 25, 18.9%) as potential therapies. Over three quarters (n = 101, 76.5%) of the included studies reported positive outcomes. Across the decade, the number of studies published increased at an annual rate of 24.0%.This review highlights the growing body of research on atrophic AMD treatments over the past decade, with antioxidant and anti-inflammatory treatments emerging as prominent, promising avenues. However, more phase III human clinical trials are needed to ensure that future therapies effectively serve the global AMD population.},
}
@article {pmid41312453,
year = {2025},
author = {Wei, L and Yan, W and Zhang, K and Gao, F and Li, Z and Pan, R and Zhang, Z and Wang, X},
title = {Allogeneic whole-eye transplantation: advancements, challenges, and future directions in vision restoration.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1691259},
pmid = {41312453},
issn = {2296-858X},
abstract = {Vision loss remains a significant global health burden, primarily driven by irreversible ocular conditions such as age-related macular degeneration (AMD), glaucoma, severe ocular trauma, and intraocular malignancies. Despite advances in retinal prosthetics and stem cell-based therapies, current treatment options are still limited in their ability to fully restore visual function. Allogeneic whole-eye transplantation (WET) has recently gained attention as a novel and potentially transformative strategy for vision restoration. This review synthesizes recent progress in the field, including advancements in microsurgical techniques, immunosuppressive protocols, and neural integration strategies, drawing on evidence from both preclinical animal models and emerging human studies. Key components, including optic nerve (ON) regeneration, vascular anastomosis, immune tolerance, and donor-recipient matching, are critically examined. Furthermore, we address ongoing barriers, including graft viability, chronic rejection, central visual pathway rewiring, and ethical considerations surrounding the procurement of donor eyes. While substantial milestones have been achieved, particularly in experimental settings, clinical translation remains in its early stages. This review highlights current limitations and proposes future directions for multidisciplinary research aimed at overcoming these challenges and advancing WET toward clinical reality.},
}
@article {pmid41311657,
year = {2025},
author = {Hanson, J and Yamamoto, M and Tsui, E and Tsui, I},
title = {Efficacy of faricimab for recalcitrant multifactorial cystoid macular edema.},
journal = {American journal of ophthalmology case reports},
volume = {40},
number = {},
pages = {102475},
pmid = {41311657},
issn = {2451-9936},
abstract = {PURPOSE: More information is emerging on faricimab-svoa (faricimab) used for etiologies beyond wet age-related macular degeneration (AMD) and diabetic macular edema (DME), including ongoing trials for use in macular edema following retinal vein occlusion (RVO). This manuscript describes a case of recalcitrant postoperative cystoid macular edema (CME), confounded by a history of branch retinal vein occlusion (BRVO), in which faricimab resulted in resolution of CME after incomplete response to topical anti-inflammation drops, intravitreal aflibercept and bevacizumab, a corticosteroid intravitreal implant, grid laser therapy, and suprachoroidal triamcinolone acetonide (SCS-TA).<br><br>OBSERVATIONS: An 83-year-old pseudophakic male with history of steroid-induced ocular hypertension and BRVO with mild preoperative CME and visual acuity (VA) of 20/160 presented with significant worsening CME following a pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peel for an epiretinal membrane (ERM) in the right eye. CME persisted for eight years despite treatment with topical anti-inflammatories, anti-VEGF injections, a dexamethasone intravitreal implant, grid laser therapy, and a SCS-TA injection. However, after 3 faricimab injections, CME resolved with a CST change from 748 &#x3bc;m to 339 &#x3bc;m and VA improved from 20/50 to 20/40.<br><br>CONCLUSIONS AND IMPORTANCE: This case demonstrates the effectiveness of faricimab in treatment of CME resistant to other therapies and the importance of continued attempts at using new agents for chronic, recurrent CME. The unique benefits of new agents like faricimab, with both VEGF and Ang-2 inhibition, may be particularly helpful in mixed or inflammatory CME when other proven therapies have failed.},
}
@article {pmid41310732,
year = {2025},
author = {Yoo, HS and Chakravarthy, H and Xi, J and Cui, J and Ai, Z and Hosseini, A and Song, J and Tan, N and Ma, N and Zhou, C and Li, B and Bell, R and Haegert, A and Le Bihan, S and Ju, MJ and Granville, DJ and Matsubara, JA},
title = {Granzyme B contributes to subretinal fibrosis in neovascular age-related macular degeneration by modulating inflammation and epithelial-mesenchymal transition.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03619-9},
pmid = {41310732},
issn = {1742-2094},
}
@article {pmid41308944,
year = {2025},
author = {Wang, L and Wang, Z},
title = {Therapeutic targeting of lncRNAs in age-related ocular disease.},
journal = {Experimental eye research},
volume = {263},
number = {},
pages = {110771},
doi = {10.1016/j.exer.2025.110771},
pmid = {41308944},
issn = {1096-0007},
abstract = {Age-related ocular diseases, including age-related macular degeneration, cataract, and glaucoma, are significant causes of visual loss and blindness worldwide. Long non-coding RNAs (lncRNAs) participate in gene regulation, epigenetic control, and cellular homeostasis, and increasing evidence implicates them in age-related ocular disorders by modulating oxidative stress, inflammation, angiogenesis, apoptosis, and extracellular matrix remodeling within ocular tissues. LncRNAs are linked to retinal degeneration, lens opacity, and optic nerve damage, supporting their promise as biomarkers and targets for treatment approaches. This review summarizes current understanding of lncRNA-related processes in age-related ocular disease and emphasizes their potential roles in diagnosis, prognosis, and treatment. An integrated view of lncRNA function in aging ocular tissues may guide precision medicine strategies to prevent or slow vision loss in older individuals.},
}
@article {pmid41308857,
year = {2025},
author = {Cen, S and Liu, S and Zhao, M and Tang, L},
title = {Comparative efficacy and safety of faricimab, aflibercept, conbercept, and ranibizumab for neovascular age-related macular degeneration: A systematic review and network meta-analysis.},
journal = {European journal of pharmacology},
volume = {1010},
number = {},
pages = {178406},
doi = {10.1016/j.ejphar.2025.178406},
pmid = {41308857},
issn = {1879-0712},
abstract = {BACKGROUND: Existing meta-analyses of anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration focus mainly on ranibizumab and aflibercept, with limited data on newer agents (faricimab, conbercept). This network meta-analysis (NMA) comprehensively compares all four key agents.<br><br>METHODS: We systematically searched multiple databases for randomized controlled trials. Bayesian random-effects network meta-analysis was conducted, with evidence certainty assessed using CINeMA (Confidence in Network Meta-Analysis).<br><br>RESULTS: Thirty-nine randomized controlled trials involving 11,548 participants were included. For best-corrected visual acuity, agents showed comparable efficacy (high to moderate evidence); differences were neither statistically nor clinically significant. Choroidal neovascularization regression showed no important differences (mostly low certainty evidence). For retinal thickness, superior reductions versus ranibizumab 0.5&#xa0;mg were observed with aflibercept 2&#xa0;mg (MD: -14.27, 95&#xa0;% CrI: -27.25, -1.75; high certainty), aflibercept 8&#xa0;mg (MD: -32.43, 95&#xa0;% CrI: -57.40, -7.75; high certainty), and conbercept 0.5&#xa0;mg (MD: -10.26, 95&#xa0;% CrI: -19.43, -0.98; moderate certainty). Faricimab required significantly fewer injections (high certainty evidence). Aflibercept 2&#xa0;mg showed better ocular safety than faricimab 6&#xa0;mg (OR: 0.58, 95&#xa0;% CrI: 0.37, 0.90) and ranibizumab 0.5&#xa0;mg (OR: 0.72, 95&#xa0;% CrI: 0.53, 0.97; high certainty).<br><br>CONCLUSION: Aflibercept and conbercept may be preferred when anatomical outcomes are prioritized, whereas faricimab's extended dosing interval could benefit treatment-adherent populations. The superior safety profile of aflibercept 2&#xa0;mg warrants consideration in risk averse patients. These differential effects support personalized therapeutic decision-making.},
}
@article {pmid41308856,
year = {2025},
author = {Chuang, CC and Chen, YS and Lu, WY and Su, SC and Liao, TY and Yang, SF and Hsieh, YH},
title = {Protective role of Oxyresveratrol against NaIO3-induced oxidative stress in RPE cells via targeting NRF2-mediated ferroptosis in vitro and in vivo.},
journal = {European journal of pharmacology},
volume = {1010},
number = {},
pages = {178402},
doi = {10.1016/j.ejphar.2025.178402},
pmid = {41308856},
issn = {1879-0712},
abstract = {Age-related macular degeneration (AMD) is a chronic retinal disorder that occurs when oxidative damages are gradually accumulated to the center of retina. Oxyresveratrol (OxyR), a naturally occurring stilbene found in many plants, has been reported to exhibit anti-inflammatory and anti-oxidative activities. To fill this gap, we explored the effect of OxyR on retinal pigment epithelial cells in response to oxidative stress and on a mouse model of AMD and further dissected the molecular mechanism underlying OxyR's actions. In this study, we demonstrated that OxyR efficiently impeded both apoptosis and ferroptosis of a human ARPE-19 cells induced by sodium iodate (NaIO3). Such protective effect of OxyR on NaIO3-induced ARPE-19 cells was accompanied with altered expression levels of NRF2, KEAP1, and several ferroptosis-related proteins. Moreover, OxyR treatment, coupled with silencing of NRF2, ferroptosis inhibitor (ferrostatin-1) or depletion of ROS, enhanced the protection of ARPE-19 cells from NaIO3-induced damages. Consistently, oral gavage of OxyR restored the reduction of retinal thickness and attenuated the upregulation of NRF2 in retinal pigment epithelium layers of NaIO3-treated mice. These results demonstrated that OxyR mitigates NaIO3-induced ARPE19 cell death via targeting NRF2-ferroptosis signaling. Our findings provided potential avenues for the use of OxyR in controlling AMD.},
}
@article {pmid41308839,
year = {2025},
author = {Wang, W and Wazny, VK and Mahadzir, MDA and Maier, AB},
title = {Multivitamin and mineral use: A rapid review of meta-analyses on health outcomes.},
journal = {Ageing research reviews},
volume = {114},
number = {},
pages = {102965},
doi = {10.1016/j.arr.2025.102965},
pmid = {41308839},
issn = {1872-9649},
abstract = {Multivitamin and mineral (MVM) supplements are among the most widely used dietary supplements globally, however, their role in promoting healthspan and longevity remains unclear. This review evaluated comprehensive findings from meta-analyses to clarify their health effects. A rapid review of MEDLINE and EMBASE identified 19 eligible meta-analyses published from 2000 to 2025, encompassing 5535,426 participants, including over 333,943 pregnancies and 904,947 children exposed to maternal MVM supplementation. Randomized controlled trials indicated that MVM use improved global cognition, episodic memory, and immediate recall in older or cognitively intact adults, reduced psychological symptoms in healthy individuals, and lowered systolic blood pressure in at-risk populations. However, no benefits were found for all-cause mortality, COVID-19 outcomes, visual acuity, or multiple cognitive domains, and a higher risk of age-related macular degeneration progression was reported. Observational studies found associations between MVM use and a reduced risk of colorectal cancer, coronary heart disease, cataracts, and fragility hip fractures, but not breast or prostate cancer, stroke, or overall mortality. During pregnancy, MVM supplementation was linked to reduced risks of small-for-gestational-age births and pediatric cancers, but not to preterm birth, stillbirth, or low birth weight. Overall, the findings revealed a lack of consistency in the definition of MVM supplementation, and substantial variability in MVM effectiveness depending on population, age, and health status. These results highlighted the importance of shifting from generalized supplementation approaches to more targeted, personalized nutritional strategies to support healthspan and longevity.},
}
@article {pmid41307906,
year = {2025},
author = {Liem, Y and Vemula, V and Lim, CC and Chong, CCY and Choo, JCJ and Cheng, CY and Sabanayagam, C},
title = {Impact of chronic kidney disease on the incidence of visual impairment and age-related eye diseases in a multi-ethnic Asian population.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04316},
pmid = {41307906},
issn = {2047-2986},
mesh = {Humans ; Middle Aged ; Aged ; Male ; Female ; *Renal Insufficiency, Chronic/complications/ethnology/epidemiology ; Singapore/epidemiology ; Incidence ; Adult ; Aged, 80 and over ; *Vision Disorders/epidemiology/ethnology ; *Eye Diseases/epidemiology/ethnology ; *Asian People/statistics &amp; numerical data ; Risk Factors ; Cataract/epidemiology ; },
abstract = {BACKGROUND: The kidney and eye share common metabolic and vascular risk factors, and chronic kidney disease (CKD) has been associated with the prevalence of visual impairment (VI). In this study, we examined the association of CKD with incident VI and major age-related eye diseases, including cataract, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, in a multi-ethnic Asian population.<br><br>METHODS: We analysed data from 6486 Chinese, Malay, and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases study at baseline (2004-11) and six-year follow-up visit (2011-17) and were free of VI and the respective eye diseases at baseline. We defined CKD (n&#x2009;=&#x2009;564; 8.7%) as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m[2], and categorised the severity of CKD into stages G1-G5. Eye examinations included refraction, slit-lamp examinations, and retinal imaging. We defined incident VI as best-corrected visual acuity <20/40 in the better eye. Eye diseases examined included cataract, AMD, retinopathy, including DR in those with diabetes and glaucoma. We examined associations between CKD, VI, and eye diseases using multivariable logistic regression models adjusted for age, gender, ethnicity, diabetes, and hypertension status, presenting the results as odds ratios (ORs) and 95% confidence intervals (CIs).<br><br>RESULTS: CKD participants had a higher incidence of any VI (14.3% vs. 3.3%; P&#x2009;<&#x2009;0.001), any AMD (8.0% vs. 5.4%; P&#x2009;<&#x2009;0.001), and cataracts (65.1% vs. 40.8%; P&#x2009;<&#x2009;0.001) than non-CKD participants. VI incidence increased with CKD severity in G1-G2 (3.3%), G3a (13.5%), and G3b-G5 (16.3%) (P&#x2009;<&#x2009;0.001). In multivariable models, CKD was associated with incident VI (OR&#x2009;=&#x2009;1.47; 95% CI&#x2009;=&#x2009;1.03-2.10) and moderate/worse DR (OR&#x2009;=&#x2009;2.62; 95% CI&#x2009;=&#x2009;1.35-5.10).<br><br>CONCLUSIONS: Our results suggest that the presence of CKD increases the risk and severity of VI and eye diseases in Asian adults. Our findings highlight the importance of regular eye exams for CKD patients to reduce the risk of VI.},
}
@article {pmid41305085,
year = {2025},
author = {Wang, MH},
title = {Explainable Artificial Intelligence Framework for Predicting Treatment Outcomes in Age-Related Macular Degeneration.},
journal = {Sensors (Basel, Switzerland)},
volume = {25},
number = {22},
pages = {},
pmid = {41305085},
issn = {1424-8220},
support = {82501368//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Macular Degeneration/therapy/diagnostic imaging/diagnosis ; Aged ; *Artificial Intelligence ; Male ; Female ; Treatment Outcome ; Tomography, Optical Coherence ; Middle Aged ; Prognosis ; Deep Learning ; Fluorescein Angiography ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, yet current tools for forecasting treatment outcomes remain limited by either the opacity of deep learning or the rigidity of rule-based systems. To address this gap, we propose a hybrid neuro-symbolic and large language model (LLM) framework that combines mechanistic disease knowledge with multimodal ophthalmic data for explainable AMD treatment prognosis. In a pilot cohort of ten surgically managed AMD patients (six men, four women; mean age 67.8 ± 6.3 years), we collected 30 structured clinical documents and 100 paired imaging series (optical coherence tomography, fundus fluorescein angiography, scanning laser ophthalmoscopy, and ocular/superficial B-scan ultrasonography). Texts were semantically annotated and mapped to standardized ontologies, while images underwent rigorous DICOM-based quality control, lesion segmentation, and quantitative biomarker extraction. A domain-specific ophthalmic knowledge graph encoded causal disease and treatment relationships, enabling neuro-symbolic reasoning to constrain and guide neural feature learning. An LLM fine-tuned on ophthalmology literature and electronic health records ingested structured biomarkers and longitudinal clinical narratives through multimodal clinical-profile prompts, producing natural-language risk explanations with explicit evidence citations. On an independent test set, the hybrid model achieved AUROC 0.94 ± 0.03, AUPRC 0.92 ± 0.04, and a Brier score of 0.07, significantly outperforming purely neural and classical Cox regression baselines (p ≤ 0.01). Explainability metrics showed that >85% of predictions were supported by high-confidence knowledge-graph rules, and >90% of generated narratives accurately cited key biomarkers. A detailed case study demonstrated real-time, individualized risk stratification-for example, predicting an >70% probability of requiring three or more anti-VEGF injections within 12 months and a ~45% risk of chronic macular edema if therapy lapsed-with predictions matching the observed clinical course. These results highlight the framework's ability to integrate multimodal evidence, provide transparent causal reasoning, and support personalized treatment planning. While limited by single-center scope and short-term follow-up, this work establishes a scalable, privacy-aware, and regulator-ready template for explainable, next-generation decision support in AMD management, with potential for expansion to larger, device-diverse cohorts and other complex retinal diseases.},
}
@article {pmid41304869,
year = {2025},
author = {Alali, NM and Aljahdali, A and AlBalawi, HB and Al Jarallah, OJ and Al Zaid, SM and Abuallut, I and ALMarek, F and Shajry, I and Alotaibi, YA and Hazzazi, MA and Magliyah, MS},
title = {Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {11},
pages = {},
pmid = {41304869},
issn = {1424-8247},
abstract = {Background/Objectives: Brolucizumab is a humanized single-chain antibody fragment with a molecular weight of approximately 26 kilodaltons (scFv, ~26 kDa) targeting all VEGF-A isoforms. Intravitreal brolucizumab (6 mg) is FDA-approved for neovascular age-related macular degeneration (nAMD) (2019) and diabetic macular edema (DME) (2022). We systematically review the literature on brolucizumab for nAMD and DME, focusing on efficacy, safety, pharmacokinetics, real-world outcomes, and cost-effectiveness in adult and pediatric patients. Methods: Our method involves a comprehensive literature search of PubMed, Embase, Scopus, Cochrane, and related databases (through late 2024) using terms including "brolucizumab," "Beovu," "neovascular AMD," "diabetic macular edema," "safety," "pharmacokinetics," and "pediatric." High-quality clinical trials, meta-analyses, regulatory documents, and real-world studies were prioritized. Results: In pivotal Phase III trials (HAWK/HARRIER for nAMD), brolucizumab 6 mg demonstrated non-inferior visual acuity (VA) gains to aflibercept, with >50% of eyes maintained on 12-week dosing and greater retinal fluid reduction. In DME trials (KESTREL/KITE), brolucizumab was similarly non-inferior to aflibercept for VA and showed superior anatomic drying, with 33-48% of eyes maintained on ≥12-week intervals. However, brolucizumab use has been associated with intraocular inflammation (IOI), retinal vasculitis, and vascular occlusion: clinical trials and post hoc analyses reported higher rates of these events than comparator agents. Real-world cohorts found IOI in ~4-10% of treated eyes, often occurring early (within 3 months) after initiation. Conclusions: In conclusion, Brolucizumab is an effective anti-VEGF option for nAMD and DME, providing durable anatomic control with fewer injections. Non-inferior vision outcomes and superior fluid resolution have been demonstrated. However, it carries a distinct risk of IOI and occlusive vasculitis, necessitating careful patient selection, dosing, and monitoring.},
}
@article {pmid41303866,
year = {2025},
author = {Kang, SG and Singh, M and Lee, G and Lee, KE and Vinayagam, R},
title = {Formulation of α-Linolenic Acid-Based Microemulsions for Age-Related Macular Degeneration: Physicochemical Tests and HET-CAM Assays for Anti-Angiogenic Activities.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {11},
pages = {},
pmid = {41303866},
issn = {1648-9144},
support = {1345370673, LINC3.0-2023-54//Ministry of Education and National Research Foundation of Korea/ ; },
mesh = {Emulsions/therapeutic use ; *alpha-Linolenic Acid/therapeutic use/pharmacology ; Animals ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy ; Chorioallantoic Membrane/drug effects ; Humans ; Chick Embryo ; Drug Delivery Systems/methods ; Chickens ; Mice ; Intravitreal Injections/methods ; },
abstract = {Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood-retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (Smix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a Smix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94-56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen's egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections.},
}
@article {pmid41303411,
year = {2025},
author = {Gyenes, A and István, L and Papp, A and Resch, M and Récsán, Z and Ecsedy, M and Szepessy, Z and Szabó, A and Lesch, B and Barcsay, G and Borbándy, &#xc1; and Sándor, GL and Nagy, ZZ and Kovács, I},
title = {Evaluation of the Duration of Good Visual Acuity During Anti-VEGF Therapy for Age-Related Macular Degeneration in Routine Clinical Practice.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303411},
issn = {1422-0067},
mesh = {Humans ; *Visual Acuity/drug effects ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Male ; Female ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy/physiopathology ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; },
abstract = {The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely inhibit VEGF. This retrospective study analysed data from patients treated with anti-VEGF injections between 2015 and 2023. We set an ETDRS score threshold of 70 (equivalent to 20/40 Snellen acuity) to calculate 'time in range' (TIR). TIR is defined as 'time spent with best-corrected visual acuity (BCVA) better than 20/40' and can highlight significant variations in the time individuals spend above the threshold during their AMD treatment. Over nine years, 30,209 aflibercept and 10,876 ranibizumab injections were administered to 6043 patients. Patients received an average of 6.8 injections. The mean BCVA at the first injection was 57.00 ± 16.15 ETDRS letters for ranibizumab patients and 58.75 ± 15.82 for aflibercept patients, with a statistically significant difference (p < 0.001). Both groups showed significant improvement in visual acuity at follow-up (aflibercept: 60.21 ± 15.53; ranibizumab: 59.43 ± 15.81; both p < 0.001). The mean time between the two consecutive injections, including both the initial loading phase and the subsequent maintenance phase, was 67.22 ± 34.08 days for ranibizumab and 72.15 ± 31.00 days for aflibercept; the difference was statistically significant (p < 0.001). After controlling for the effect of initial BCVA and time between injections, patients who received aflibercept had a significantly higher average TIR (60.90 ± 36.27 days vs. 56.55 ± 38.78 days, p < 0.001), and significantly more likely to achieve >70 letters at the next visit (OR: 1.10; 95% CI: 1.05-1.15; p < 0.001) compared to patients receiving ranibizumab. Aflibercept treatment improves the likelihood of maintaining good BCVA by 10% compared to ranibizumab in patients receiving intravitreal anti-VEGF treatment for nAMD. Furthermore, the beneficial effects of aflibercept treatment are observed with less frequent dosing. Our results suggest that using anti-VEGF compounds that target multiple domains provides a detectable advantage in treating age-related macular degeneration, particularly when these agents have a longer duration of action.},
}
@article {pmid41303406,
year = {2025},
author = {Chao, WW and Chao, HW and Peng, PH and Lee, YT and Chao, HM},
title = {Retinal Ischemia: Therapeutic Effects and Mechanisms of Paeoniflorin.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303406},
issn = {1422-0067},
mesh = {Animals ; *Glucosides/pharmacology/therapeutic use ; *Monoterpenes/pharmacology/therapeutic use ; Rats ; Rats, Wistar ; Male ; Vascular Endothelial Growth Factor A/metabolism ; *Ischemia/drug therapy/metabolism/pathology ; Disease Models, Animal ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Retinal Diseases/drug therapy/metabolism/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Cell Survival/drug effects ; Reperfusion Injury/drug therapy/metabolism/pathology ; Apoptosis/drug effects ; Neuroprotective Agents/pharmacology ; },
abstract = {Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H2O2) or by subjecting retinal neuronal cells to 8 h of oxygen-glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties.},
}
@article {pmid41303405,
year = {2025},
author = {Noreen, S and Lim, SS and Lee, D},
title = {Preventive and Protective Effects of Nicotinamide Adenine Dinucleotide Boosters in Aging and Retinal Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303405},
issn = {1422-0067},
support = {RS-2021-NR060133//NRF/ ; },
mesh = {Humans ; *NAD/metabolism ; Animals ; *Aging/metabolism/drug effects ; *Retinal Diseases/metabolism/prevention &amp; control/drug therapy ; Niacinamide/analogs &amp; derivatives/pharmacology/therapeutic use ; Diabetic Retinopathy/metabolism/drug therapy/prevention &amp; control ; Macular Degeneration/metabolism/drug therapy ; Mitochondria/metabolism/drug effects ; Retina/metabolism/drug effects ; Oxidative Stress/drug effects ; *Protective Agents/pharmacology ; Nicotinamide Mononucleotide/pharmacology/therapeutic use ; Pyridinium Compounds ; },
abstract = {Nicotinamide adenine dinucleotide (NAD[+]) boosting can sustain energy metabolism and neurovascular stability in the retinal tissue. Depletion of NAD[+] is linked to the development of pathological retinal conditions, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction, oxidative stress, and inflammation occur in these diseases. This review summarizes substantial evidence of therapeutic NAD[+] boosters, including nicotinamide, nicotinamide mononucleotide, or nicotinamide riboside. They help improve mitochondrial function and lessen neurovascular injury. We also emphasize the importance of natural products and sirtuins in facilitating cytoprotective effects through the regulation of mitochondrial balance and inflammation. Developments in drug delivery methods, such as nanoparticle encapsulation and targeted eye treatments, are promising for enhancing the bioavailability and effectiveness of NAD[+] boosters. The novelty of this work is its combination of mechanistic insights regarding NAD[+] metabolism with efficacy data from preclinical studies. Furthermore, natural products may work together to boost their therapeutic effects against retinal damage. Together, our review article highlights NAD[+] metabolism as a potential therapeutic target for addressing retinal degeneration and maintaining vision in aging, neurologic disorders, and various metabolic diseases, including diabetes.},
}
@article {pmid41303260,
year = {2025},
author = {Lee, SY and Hwang, DD},
title = {Short-Term Effects of Intravitreal Ranibizumab Biosimilar Injections in Patients with Neovascular Age-Related Macular Degeneration on Retinal Nerve Fiber Layer Thickness.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41303260},
issn = {2077-0383},
abstract = {Background/Objectives: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD), but concerns remain regarding its potential effects on optic nerve structure. Evidence on the structural safety of ranibizumab biosimilars, including LucenBS[®], is still limited. This study aimed to investigate the short-term effects of intravitreal LucenBS[®] injections on peripapillary retinal nerve fiber layer (RNFL) thickness in previously treated nAMD patients using optical coherence tomography (OCT). Methods: This retrospective, observational case series included 24 eyes from 24 nAMD patients who had previously received anti-VEGF agents other than ranibizumab biosimilar. In bilateral cases, the eye that developed nAMD earlier was selected. Patients received between one and three LucenBS[®] injections, and the mean follow-up period after the final injection was 11.92 ± 4.81 weeks. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), and peripapillary RNFL thickness were assessed before and after each injection using spectral-domain OCT. Sectoral and global RNFL values were compared using the Wilcoxon signed-rank test. Results: The mean age of participants was 74.6 ± 9.0 years, and baseline BCVA and IOP were 0.83 ± 0.66 logMAR and 14.88 ± 2.80 mmHg, respectively. RNFL thickness showed no significant changes in either global or sectoral regions after any injection (all p > 0.05). CMT significantly decreased after the first injection (p = 0.007), but remained stable with subsequent treatments. BCVA remained stable after the first and second injections, but slightly worsened after the third injection (p = 0.012). IOP showed no significant changes at any time point. Conclusions: Short-term intravitreal LucenBS[®] injections did not induce structural alterations in the peripapillary RNFL, supporting their short-term ocular safety in previously treated nAMD patients. Although CMT improved after the first injection, functional and anatomical responses varied with repeated dosing. Larger, long-term studies are required to further validate the structural and functional safety of ranibizumab biosimilars in nAMD management.},
}
@article {pmid41303214,
year = {2025},
author = {Wu, KY and Qian, SY and Camiré, A and Kim, DT and Giunta, M},
title = {Aflibercept for Wet Age-Related Macular Degeneration: A Prospective, Randomized Trial Comparing Treat-And-Extend and Fixed Bimonthly Dosing.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41303214},
issn = {2077-0383},
support = {Unknown//Bayer (Canada)/ ; },
abstract = {Background/Objectives: Currently, treatments for age-related macular degeneration (AMD) consist of regular intravitreal injections that exert significant pressure on healthcare systems via their high labor costs and economic burden. To address this, our study's goal is to propose new treatment protocols by comparing the efficacy of bimonthly fixed dosing aflibercept injections versus the treat-and-extend (T&amp;E) approach for wet AMD. Secondary objectives included categorical best-corrected visual acuity (BCVA) changes, anatomical outcomes, treatment intervals, and adverse events. Methods: This study is a 1-year randomized, open-label, prospective trial that included 44 eyes from 44 patients, 32 in the T&amp;E arm and 12 in the bimonthly arm. Treatment-naïve AMD patients with neovascularization were randomized to a bimonthly fixed dosing group or a T&amp;E group after receiving 3 consecutive monthly aflibercept injections. Following the induction doses, retreatment intervals for patients in the T&amp;E arm were adjusted based on a predetermined algorithm. Results: Over 12 months, mean BCVA improvements were 5.0 letters in the bimonthly group and 4.1 in the T&amp;E group (p = 0.096 for non-inferiority test). On average, T&amp;E patients received 9.6 injections compared to 7.7 for those in the fixed dosing group (p < 0.001). Anatomical outcomes were comparable in both treatment arms. Conclusions: In our trial, the T&amp;E approach provided significant visual improvements, but did not meet the threshold for non-inferiority when compared to fixed bimonthly dosing. It was also unable to minimize treatment burden over the course of the first year of injections. Further research is required to optimize the T&amp;E algorithm with aflibercept.},
}
@article {pmid41302976,
year = {2025},
author = {Molin, C and Midena, E and Convento, E and Midena, G and Pilotto, E},
title = {Fixation Stability as a Surrogate for Reading Abilities in Age-Related Macular Degeneration: A Perspective.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41302976},
issn = {2077-0383},
abstract = {Age-related macular degeneration (AMD) significantly impacts central vision, fixation site and stability and reading abilities. This work aims to analyze the relationship between retinal fixation parameters measured using microperimetry and reading performance in patients with AMD. We identified the role of fixation stability measurement in the evaluation of reading abilities and discussed its implications both in clinical practice and in clinical trials. Our analysis highlights the importance of retinal fixation assessment as a precise surrogate for evaluating reading ability outcomes in AMD patients and as new clinical endpoint to demonstrate the functional effects of present and emerging target therapies.},
}
@article {pmid41302082,
year = {2025},
author = {Liesenhoff, C and Meyrl, C and Krause, D and Eckardt, F and Lorger, A and Deiters, V and Schiefelbein, J and Klaas, JE and Schworm, B and Priglinger, SG and Siedlecki, J},
title = {High-Dose 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration: Who Is Being Treated with This New Agent?.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
pmid = {41302082},
issn = {2075-1729},
abstract = {Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD treated with 8 mg aflibercept. Demographic data, multimodal imaging and treatment parameters were recorded. Reasons for treatment with 8 mg aflibercept were analyzed. Results: Thirty-four consecutive eyes of 31 patients (mean age 78.6 ± 8.9 years) were identified. There were 22 women (70.1%) and 9 men (29.9%). In all eyes (100%), 8 mg Aflibercept was applied as switching therapy. Prior to switching, the mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 3.9 ± 2.9 years, pretreatment amounted to a mean of 34.5 ± 26.3 injections, equaling 9.2 ± 2.4 injections/year, and the mean visual acuity (VA) was 0.4 ± 0.4 logMAR. The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases. Reasons for switching included (A) recalcitrant nAMD with persistent fluid despite q4w dosing (17 eyes, 50%), (B) the wish for interval extension (15 eyes, 44%) and (C) macular hemorrhage (2 eyes, 6%). In group B, two-thirds of eyes (10/15, 66.7%) were maintained at ≤q6w prior to switching. Conclusions: In this study, high-dose 8 mg aflibercept was exclusively used as a switch therapy. Most eyes (76%) switched were from pretreatment with 2 mg aflibercept. The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept.},
}
@article {pmid41301918,
year = {2025},
author = {Lee, Y and Seo, JH},
title = {Potential Causal Effects of Cystatin C on Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301918},
issn = {2227-9059},
support = {VHSMC24002//Veterans Health Service Medical Center Research Grant/ ; },
abstract = {Background/Objectives: Previous studies have shown an association between kidney function and age-related macular degeneration (AMD). This study aims to assess whether the kidney function-related parameters of serum cystatin C and creatinine levels are associated with increased risk of AMD and its subtypes. Methods: Genetic instruments for variants associated with serum cystatin C and creatinine levels as exposure at genome-wide significance (p < 5.0 × 10[-8]) were obtained from the UK Biobank. Genetic data for AMD and its subtypes were obtained from the FinnGen project. A two-sample Mendelian randomization analysis was performed to evaluate the causal effects of serum cystatin C and creatinine levels on AMD and its subtypes. Results: Using an inverse-variance weighted approach, higher cystatin C levels are associated with an increased risk of AMD [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.04 to 1.22, p = 0.004 for overall AMD; OR = 1.14, 95% CI: 1.04 to 1.25, p = 0.007 for dry AMD; OR = 1.14, 95% CI: 1.03 to 1.26, p = 0.011 for wet AMD]. However, serum creatinine levels did not significantly impact the risk of AMD or its subtypes. Conclusions: This study provides genetic evidence that higher cystatin C levels may be a causal risk factor for AMD and its subtypes, whereas serum creatinine was not. This result implies the need to investigate the effect of cystatin C on AMD potentially independent of kidney function.},
}
@article {pmid41301509,
year = {2025},
author = {Nardella, M and Pellegrini, M and Yu, AC and Adamo, GG and Mura, M and Busin, M},
title = {Nanotechnology-Based Delivery Systems and Retinal Pigment Epithelium: Advances, Targeting Approaches, and Translational Challenges.},
journal = {Biomolecules},
volume = {15},
number = {11},
pages = {},
pmid = {41301509},
issn = {2218-273X},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Drug Delivery Systems/methods ; Animals ; *Nanotechnology/methods ; Translational Research, Biomedical ; Nanomedicine/methods ; Macular Degeneration/drug therapy ; Retinal Diseases/drug therapy ; Nanoparticles/chemistry ; },
abstract = {The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application.},
}
@article {pmid41301489,
year = {2025},
author = {Intonti, S and Olivieri, C and Reibaldi, M and Borrelli, E and Curcio, C and Conedera, FM},
title = {Translational Molecular and Fluid Biomarkers for Age-Related Macular Degeneration: Practical Insights from Animal Models and Humans.},
journal = {Biomolecules},
volume = {15},
number = {11},
pages = {},
pmid = {41301489},
issn = {2218-273X},
support = {PZ00P3_223803/SNSF_/Swiss National Science Foundation/Switzerland ; },
mesh = {Humans ; *Biomarkers/metabolism ; Animals ; *Macular Degeneration/metabolism/diagnosis/pathology/genetics ; Disease Models, Animal ; Oxidative Stress ; Mice ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss. Its pathogenesis is complex and multifactorial, involving genetic predisposition, inflammation, oxidative stress, and environmental influences, which underscores the need to better understand biomarkers associated with the disease. This review provides a comprehensive translational overview of biomarkers linked to both dry and wet forms of AMD by integrating findings from human studies and preclinical mouse models, including chemical, genetic, and laser-induced paradigms. It outlines key tissue, fluid, and systemic biomarkers related to oxidative stress, inflammation, complement activation, extracellular matrix remodeling, angiogenesis, and gut microbiota alterations. The main findings highlight similarities and differences between human AMD and animal models, identify challenges in biomarker validation, and emphasize the potential of combining biomarker profiles from ocular tissues, blood, tear fluid, aqueous and vitreous humor, and gut microbiome samples to improve early diagnosis, therapeutic monitoring, and personalized treatment strategies. These insights suggest that integrating experimental and clinical biomarker data could advance precision medicine in AMD, facilitating better early detection and individualized therapies. Future research should aim to bridge these datasets to optimize biomarker-driven approaches for AMD management.},
}
@article {pmid41300437,
year = {2025},
author = {Hong, SJ and Lee, DH and Choi, JW and Lee, H and Sung, Y and Kim, GJ},
title = {Nrf2 Activated by PD-MSCs Attenuates Oxidative Stress in a Hydrogen Peroxide-Injured Retinal Pigment Epithelial Cell Line.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {11},
pages = {},
pmid = {41300437},
issn = {2076-3921},
support = {RS - 2025 - 431 02313877//Industry - Academia - Research Institute (IAR) Collabo R&amp;D Fund Grant funded by the Korean Government/ ; },
abstract = {Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H2O2) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H2O2 treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H2O2 treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H2O2-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress.},
}
@article {pmid41300254,
year = {2025},
author = {Shi, C and Lee, J and Shi, D and Wang, G and Yuan, F and Lai, TYY and Liu, J and Lu, Y and Liu, D and Qin, B and Zee, BC},
title = {AI-Based Retinal Image Analysis for the Detection of Choroidal Neovascular Age-Related Macular Degeneration (AMD) and Its Association with Brain Health.},
journal = {Brain sciences},
volume = {15},
number = {11},
pages = {},
pmid = {41300254},
issn = {2076-3425},
abstract = {Purpose: This study aims to develop a method for detecting referable (intermediate and advanced) age-related macular degeneration (AMD) and neovascular AMD, as well as providing an automatic segmentation of choroidal neovascularisation (CNV) on colour fundus retinal images. We also demonstrated that brain health risk scores estimated by AI-based Retinal Image Analysis (ARIA), such as white matter hyperintensities and depression, are significantly associated with AMD and neovascular AMD. Methods: A primary dataset of 1480 retinal images was collected from Zhongshan Hospital of Fudan University for training and 10-fold cross-validation. Additionally, two validation subdataset comprising 238 images (retinal images and wide-field images) were used. Using fluorescein angiography-based labels, we applied the InceptionResNetV2 deep network with the ARIA method to detect AMD, and a transfer ResNet50_Unet was used to segment CNV. The risks of cerebral white matter hyperintensities and depression were estimated using an AI-based Retinal Image Analysis approach. Results: In a 10-fold cross-validation, we achieved sensitivities of 97.4% and 98.1%, specificities of 96.8% and 96.1%, and accuracies of 97.0% and 96.4% in detecting referable AMD and neovascular AMD, respectively. In the external validation, we achieved accuracies of 92.9% and 93.7% and AUCs of 0.967 and 0.967, respectively. The performances on two validation sub-datasets show no statistically significant difference in detecting referable AMD (p = 0.704) and neovascular AMD (p = 0.213). In the segmentation of CNV, we achieved a global accuracy of 93.03%, a mean accuracy of 91.83%, a mean intersection over union (IoU) of 68.7%, a weighted IoU of 89.63%, and a mean boundary F1 (BF) of 67.77%. Conclusions: The proposed method shows promising results as a highly efficient and cost-effective screening tool for detecting neovascular and referable AMD on both retinal and wide-field images, and providing critical insights into CNV. Its implementation could be particularly valuable in resource-limited settings, enabling timely referrals, enhancing patient care, and supporting decision-making across AMD classifications. In addition, we demonstrated that AMD and neovascular AMD are significantly associated with increased risks of WMH and depression.},
}
@article {pmid41297526,
year = {2025},
author = {Paneerselvam, GS and Wai, NJ and Sheng, LJ and Kenneth, LKC},
title = {Cost-Effectiveness of Vascular Endothelial Growth Factor Inhibitors in the Management of Wet Age-Related Macular Degeneration: A Systematic Review.},
journal = {Value in health regional issues},
volume = {53},
number = {},
pages = {101542},
doi = {10.1016/j.vhri.2025.101542},
pmid = {41297526},
issn = {2212-1102},
abstract = {OBJECTIVES: To evaluate the cost-effectiveness of VEGF inhibitors, ranibizumab, aflibercept, bevacizumab, brolucizumab, pegaptanib, and conbercept for wAMD treatment.<br><br>METHODS: A systematic search was conducted in PubMed, Cochrane, and SpringerLink databases to identify cost-effectiveness analyses and cost-utility analyses related to wAMD treatment. Eligible studies were assessed using Drummond's 10-point checklist to evaluate methodological quality. The extracted data included intervention costs, quality-adjusted life-years, and incremental cost-effectiveness ratios.<br><br>RESULTS: Twenty-two studies met the inclusion criteria. Bevacizumab and brolucizumab were frequently reported as cost-effective alternatives, offering comparable or superior visual outcomes at lower costs than ranibizumab or aflibercept. Pegaptanib was consistently less cost-effective. Findings for ranibizumab versus aflibercept varied by treatment regimen and analytic assumptions. Across studies, cost-effectiveness estimates were influenced by model perspective, time horizon, exclusion of adverse events, and single-eye modeling. A further limitation is that in contexts of non-inferior efficacy, small incremental quality-adjusted life-years differences may artificially inflate incremental cost-effectiveness ratios, potentially overstating the costs relative to benefits.<br><br>CONCLUSIONS: Decision making in wAMD treatment requires more thorough economic evaluations that incorporate standardized methodologies and lengthy cost assessments.},
}
@article {pmid41297424,
year = {2025},
author = {Zhou, L and Ma, Y and Li, X and Cao, G},
title = {Gut-eye axis in ophthalmic diseases: Focus on ocular neurodegeneration.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {193},
number = {},
pages = {118800},
doi = {10.1016/j.biopha.2025.118800},
pmid = {41297424},
issn = {1950-6007},
abstract = {Ocular neurodegeneration comprises a group of complex processes that severely affect visual function and is recognized as a key pathogenetic process in a variety of blinding ocular diseases, including glaucoma, diabetic retinopathy, age-related macular degeneration and retinitis pigmentosa. Although these diseases have different etiologies and mechanisms, apoptosis, metabolic disorders and oxidative damage are common features shared by all of them. Increasing evidence indicates that gut microbiota regulates distant organs by engaging in the host's neural, endocrine, immune regulation and even intercellular information. However，in ocular degenerative diseases, specific gut microbiota and their metabolites play an important role in ocular degenerative diseases. Therefore, in this review, we summarize the pathways through which the "gut-eye axis" functions and the mechanisms by which it interacts with ocular degenerative diseases, as well as the alterations in gut microbiota profiles observed in several common ocular degenerative diseases. Additionally, we provide an outlook on the clinical application of the "gut-eye axis", including its potential diagnostic, therapeutic, and adjunctive therapies.},
}
@article {pmid41294847,
year = {2025},
author = {Alam, J and Ponnam, A and Souvangini, A and Gopi, S and Ildefonso, CJ and Biswal, MR},
title = {EPO-R76E Enhances Retinal Pigment Epithelium Viability Under Mitochondrial Oxidative Stress Induced by Paraquat.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
pmid = {41294847},
issn = {2073-4409},
support = {R01 EY033415/EY/NEI NIH HHS/United States ; R01EY033415/EY/NEI NIH HHS/United States ; },
mesh = {*Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; *Mitochondria/metabolism/drug effects ; *Paraquat/toxicity/pharmacology ; *Erythropoietin/genetics/metabolism ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; NF-E2-Related Factor 2/metabolism ; Apoptosis/drug effects ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, primarily driven by oxidative stress-induced degeneration of retinal pigment epithelium (RPE). Erythropoietin (EPO), a hematopoietic cytokine with neuroprotective properties, has been shown to reduce apoptosis and retinal degeneration. In this study, we examined the cytoprotective role of a non-erythropoietic EPO variant, EPO-R76E, in suppressing oxidative stress and mitochondrial dysfunction related to oxidative stress in RPE cells. Stable ARPE-19 cell lines expressing EPO-R76E were generated via lentiviral transduction and exposed to paraquat to induce oxidative stress. Oxidative stress was induced using paraquat. EPO-R76E expression conferred increased cell viability and resistance to mitochondrial damage, as assessed by cytotoxicity assays. Western blot analysis revealed reduced expression of ferritin and p62/SQSTM1, diminished activation of p-AMPK and NRF2, and restoration of GPX4 levels, indicating enhanced antioxidant defenses. Moreover, intracellular iron accumulation and reactive oxygen species were significantly reduced in EPO-R76E-expressing cells exposed to paraquat. These findings suggest that EPO-R76E promotes mitochondrial homeostasis and modulates oxidative stress pathways. Our study positions EPO-R76E as a promising therapeutic candidate for halting RPE degeneration in AMD.},
}
@article {pmid41294302,
year = {2025},
author = {Quarta, A and Corradetti, G and Romano, F and Trinco, A and Feo, A and Corvi, F and Nardi, C and Alhelaly, M and Abbasgholizadeh, R and Chujo, S and Popovic, M and Soylu, C and Chung, YC and Kwak, HD and Rattu, R and Nittala, MG and Staurenghi, G and Sadda, SR},
title = {Distinct Profiles of Choriocapillaris Involvement in Extensive Macular Atrophy With Pseudodrusen-Like Appearance and Geographic Atrophy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {14},
pages = {64},
pmid = {41294302},
issn = {1552-5783},
mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/etiology ; Retrospective Studies ; Female ; *Choroid/blood supply ; Cross-Sectional Studies ; Male ; Tomography, Optical Coherence/methods ; Aged ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Retinal Drusen/diagnosis/physiopathology ; Capillaries/pathology/physiopathology ; *Macular Degeneration/complications/diagnosis/physiopathology ; Visual Acuity ; Fundus Oculi ; Middle Aged ; Regional Blood Flow/physiology ; },
abstract = {PURPOSE: To quantitatively compare choriocapillaris flow deficit percentages (CCFD%) between eyes with extensive macular atrophy with pseudodrusen-like appearance (EMAP) and geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and to identify predictive factors for CCFD% at the atrophy margin.<br><br>METHODS: This retrospective cross-sectional study included 53 eyes (27 with GA and 26 with EMAP). CCFD% were computed within a 500-&#xb5;m-wide marginal zone (CCFD%_M) and beyond the margin (CCFD%_BM) using compensated en face optical coherence tomography angiography (OCTA) images. Atrophy-to-fovea distance (AFD) was quantified by pixel-wise Euclidean analysis.<br><br>RESULTS: Eyes with EMAP demonstrated significantly higher CCFD% compared to GA both at the atrophy margin (CCFD%_M, P < 0.05) and beyond (CCFD%_BM, P < 0.01). In univariable analysis, belonging to the GA group was associated with a 5.9-unit reduction in CCFD%_M, reflecting a substantial preservation of choriocapillaris (CC) perfusion in GA relative to EMAP. AFD was greater in EMAP (2.35 &#xb1; 0.56 mm) than GA (1.74 &#xb1; 0.55 mm; P = 0.014) suggesting more eccentric positioning of the lesions in the former. A multivariable mixed-effects model confirmed disease subtype (EMAP vs. GA) as an independent determinant of CC impairment with EMAP associated with a significantly higher CCFD%_M (P < 0.01).<br><br>CONCLUSIONS: CC impairment is more pronounced in EMAP than in GA, with EMAP exhibiting more extensive and diffuse CCFD, particularly at the atrophy margins. This pattern may reflect a more aggressive vascular compromise in EMAP. These findings underscore a distinct CC pathoanatomy between the two conditions, with implications for disease progression and therapeutic targeting.},
}
@article {pmid41293996,
year = {2025},
author = {Xin, X and Zhao, X and Han, X and Pu, W},
title = {ASNS Regulates H2O2-Induced Senescence, Oxidative Stress, and Glucose Metabolism in ARPE-19 Cells by Modulating USP13 Expression.},
journal = {BioFactors (Oxford, England)},
volume = {51},
number = {6},
pages = {e70057},
pmid = {41293996},
issn = {1872-8081},
support = {2023GLLH0239//Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of InnerMongolia Academyof Medical Sciences/ ; 2023YK17//Scientific Research Program of Aerospace Medical and Healthcare Technology Group Co./ ; },
mesh = {Oxidative Stress/drug effects ; Humans ; Hydrogen Peroxide/pharmacology ; *Glucose/metabolism ; Cellular Senescence/drug effects ; Animals ; Cell Line ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Macular Degeneration/genetics/metabolism/pathology ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a common degenerative disease of the eye that ultimately leads to irreversible vision loss. Asparagine synthase (ASNS) is an aminotransferase, and its low expression is associated with retinal damage. The present study centered on the protective effect of ASNS on retinal epithelial cells. We found that in the AMD cell model, overexpression of ASNS reduced SA-β-gal staining and ROS production, and increased cell viability in H2O2-treated ARPE-19 cells. In addition, overexpression of ASNS increased glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) and enhanced the expression of glycolytic markers. Molecular mechanistic studies revealed that ASNS was highly bound to USP13 protein and increased USP13 expression. Furthermore, ASNS protected the retinal epithelium from oxidative stress damage in an animal model of AMD. Taken together, these findings suggest that the ASNS/USP13 axis plays an important regulatory role in AMD development. Our findings not only emphasized the understanding of the role of glucose metabolism in AMD, but also identified a promising target for future AMD therapy.},
}
@article {pmid41293704,
year = {2025},
author = {Guo, Y and Hormel, TT and Wu, AL and Gao, M and Hwang, TS and Bailey, ST and Jia, Y},
title = {AI-aided segmentation of four types of drusen in volumetric OCT.},
journal = {Biomedical optics express},
volume = {16},
number = {11},
pages = {4380-4391},
pmid = {41293704},
issn = {2156-7085},
abstract = {Drusen are a hallmark biomarker of age-related macular degeneration (AMD), with their size, number, and morphology (type) closely linked to disease severity and progression. Accurate segmentation and classification of drusen from optical coherence tomography (OCT) images are essential for objective AMD assessment and monitoring. In this work, we present a deep learning framework that combines a convolutional neural network for automated drusen segmentation with a dedicated classification module to distinguish four clinically relevant, distinct drusen types based on segmentation output. We evaluated our approach on a comprehensive dataset and achieved a mean Dice score of 0.74 ± 0.21 for voxel-wise segmentation accuracy and a critical success index of 0.69 ± 0.24 for drusen count accuracy. This method demonstrates substantial improvements in the quantitative drusen analysis and offers a promising tool for enhanced AMD diagnosis and tracking of disease progression.},
}
@article {pmid41293061,
year = {2025},
author = {Lorenzi, M and Ebohon, S and Kissner, J and Comiskey, J and Paap, M and Bouchet, C and Garnham, A and Wissinger, E},
title = {Network Meta-Analysis of Bevacizumab Gamma Versus Competing Interventions for Treating Neovascular Age-Related Macular Degeneration in the United Kingdom.},
journal = {Journal of market access &amp; health policy},
volume = {13},
number = {4},
pages = {58},
pmid = {41293061},
issn = {2001-6689},
abstract = {This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis (NMA). An SLR was conducted to identify randomized controlled trials (RCTs) of anti-vascular endothelial growth factor (anti-VEGF) therapies for the treatment of nAMD in adult patients relevant to the UK context. The included anti-VEGF treatments were ranibizumab, aflibercept, faricimab, and bevacizumab gamma. Bayesian NMA models were used to estimate relative efficacy in terms of change from baseline (CFB) in best-corrected visual acuity (BCVA) at 12 months, the proportion of patients gaining 15 or more letters at 12 months, and the proportion of patients losing less than 15 letters at 12 months. Twenty-two relevant RCTs were included in the NMA. At 12 months, all anti-VEGF treatments were similarly efficacious to ranibizumab 0.5 mg every four weeks (Q4W) in terms of CFB in BCVA, the proportion of patients gaining 15 or more letters, and the proportion of patients losing less than 15 letters (except for ranibizumab 0.5 mg every 12 weeks [Q12W] and ranibizumab 0.5 mg pro re nata [PRN]). Bevacizumab gamma provided similar improvements in visual acuity to other anti-VEGF treatments.},
}
@article {pmid41292308,
year = {2025},
author = {Kim, TR and Kim, TG and Choi, J and Yu, SY and Kim, K},
title = {Quantitative Analysis of Drusen in Korean Patients: A 36-Month Follow-Up Study.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2025.0104},
pmid = {41292308},
issn = {2092-9382},
abstract = {PURPOSE: This study aimed to quantitatively evaluate longitudinal changes in drusen area and volume over 36 months in Korean patients and to identify the factors associated with these changes and the development of advanced age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective study, 38 eyes from 38 patients diagnosed with drusen were analyzed. The drusen area and volume were measured using spectral-domain optical coherence tomography (SD-OCT, Cirrus 5000; Carl Zeiss Meditec, Dublin, CA, USA) with an automated retinal pigment epithelium (RPE) elevation map algorithm. To minimize bias from variable follow-up intervals, an annualized classification framework was adopted. Based on percentage change in drusen area within the 5-mm circle, eyes were categorized as progressed (increase >20%), stable (change within &#xb1;20%), or regressing (decrease >20%).<br><br>RESULTS: Both drusen area and volume increased significantly up to 24 months (area: p = 0.003; volume: p = 0.028) and then showed a modest decline at 36 months, remaining above baseline levels. No significant difference in the proportions of progressed, stable, or regressing eyes was observed across 12-month intervals or compared with baseline (all p > 0.05). A larger baseline 5-mm drusen area was significantly associated with the development of advanced AMD (adjusted odds ratio = 2.818; 95% confidence interval, 1.022-7.767; p = 0.045). Eyes that exhibited at least one episode of drusen regression showed a higher incidence of advanced AMD (36.8% vs 5.3%; p = 0.042).<br><br>CONCLUSIONS: Drusen in Korean patients demonstrated dynamic morphological remodeling over time. Drusen regression was not a benign phenomenon but rather a potential high-risk marker for progression to advanced AMD. These findings highlight the importance of population-specific, quantitative SD-OCT monitoring for early risk stratification in East Asian eyes.},
}
@article {pmid41284475,
year = {2025},
author = {Cui, Y and Song, Z and Wang, X},
title = {Bisphosphonate-related ocular adverse events: a pharmacovigilance study based on the FAERS database.},
journal = {Endocrine connections},
volume = {},
number = {},
pages = {},
doi = {10.1530/EC-25-0482},
pmid = {41284475},
issn = {2049-3614},
abstract = {This retrospective study aimed to identify and characterize signals of ocular adverse events (AEs) related to bisphosphonates (BPs) using FDA Adverse Event Reporting System (FAERS) data (2004Q1-2024Q3) to inform future safety investigations. Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods to identify BP-related ocular AE signals. Additionally, a modified ROR method was utilized to examine differences across gender and age. Among 6,965 ocular AE reports for five BPs (alendronate, zoledronate, pamidronate, risedronate, and ibandronate), 136 positive signals were identified, predominantly unlisted in drug labels. Notable risks included ocular inflammatory AEs (especially zoledronate) and novel risk signals such as cataract, glaucoma, and macular degeneration. Standardized MedDRA queries (SMQ) linked BPs to 11 eye disorders, with scleral disorders common to all five BPs and pamidronate involving the broadest SMQ categories. Ocular AEs for alendronate, zoledronate, and pamidronate exhibited age-related differences, while those for alendronate and zoledronate showed gender differences. This study identifies high-risk and novel ocular AEs related to BPs. These findings warrant further validation in future studies.},
}
@article {pmid41283579,
year = {2025},
author = {Cao, JA and Zhou, AW and Teagle, GM and Baumann, LM and Sahraravand, RA and Wong, CW and De Zanet, S and Jovic, N and Steiner, P and Patel, SB and Minaker, SA and MacCumber, MW and Brown, DM and Al-Khersan, H and Wykoff, CC},
title = {Geographic Atrophy Progression in Clinical Practice Before and After Pegcetacoplan Treatment.},
journal = {Vision (Basel, Switzerland)},
volume = {9},
number = {4},
pages = {},
pmid = {41283579},
issn = {2411-5150},
support = {N/A//Texas Retina Research Foundation (TRRF), Houston, Texas/ ; },
abstract = {This retrospective study evaluated changes in ocular characteristics and retinal pigment epithelium (RPE) and photoreceptor ellipsoid zone (EZ) depletion rates before and after intravitreal pegcetacoplan initiation in clinical practice. A total of 168 eyes from 110 patients with GA secondary to age-related macular degeneration (AMD) who received at least 3 pegcetacoplan injections were included. Data was collected from 5 years before to 9 months after pegcetacoplan initiation. RPE and EZ depletion areas were measured using an automated artificial intelligence (AI) algorithm on optical coherence tomography (OCT) images. At baseline, 76 eyes (45.2%) had concurrent neovascular AMD (nAMD), with mean RPE and EZ depletion areas of 3.3 mm[2] and 4.9 mm[2], respectively. By pegcetacoplan initiation, these increased to 8.6 mm[2] and 11.2 mm[2], respectively, with 151 eyes (89.9%) having concurrent nAMD and 155 eyes (92.3%) having subfoveal GA. Pre-treatment to post-treatment RPE and EZ square root depletion rates decreased from 0.25 mm/year to 0.096 mm/year, and 0.26 mm/year to 0.049 mm/year, respectively. Mean best-recorded visual acuity (BRVA) worsened by 0.05 logMAR annually before and after treatment. These real-world findings align with data from the pegcetacoplan phase 3 trials, showing reduced RPE and EZ depletion rates without changes in rates of BRVA loss. Additional studies are warranted.},
}
@article {pmid41283408,
year = {2025},
author = {Barranco Garcia, J and Ferrazzini, T and Coito, A and Brügger, D and Abegg, M},
title = {Recovery of the Pupillary Response After Light Adaptation Is Slowed in Patients with Age-Related Macular Degeneration.},
journal = {Journal of eye movement research},
volume = {18},
number = {6},
pages = {},
pmid = {41283408},
issn = {1995-8692},
abstract = {Purpose: This study evaluates a novel, non-invasive method using a virtual reality (VR) headset with integrated eye trackers to assess retinal function by measuring the recovery of the pupillary response after light adaptation in patients with age-related macular degeneration (AMD). Methods: In this pilot study, fourteen patients with clinically confirmed AMD and 14 age-matched healthy controls were exposed to alternating bright and dark stimuli using a VR headset. The dark stimulus duration increased incrementally by 100 milliseconds per trial, repeated over 50 cycles. The pupillary response to the re-onset of brightness was recorded. Data were analyzed using a linear mixed-effects model to compare recovery patterns between groups and a convolutional neural network to evaluate diagnostic accuracy. Results: The pupillary response amplitude increased with longer dark stimuli, i.e., the longer the eye was exposed to darkness the bigger was the subsequent pupillary amplitude. This pupillary recovery was significantly slowed by age and by the presence of macular degeneration. Test diagnostic accuracy for AMD was approximately 92%, with a sensitivity of 90% and a specificity of 70%. Conclusions: This proof-of-concept study demonstrates that consumer-grade VR headsets with integrated eye tracking can detect retinal dysfunction associated with AMD. The method offers a fast, accessible, and potentially scalable approach for retinal disease screening and monitoring. Further optimization and validation in larger cohorts are needed to confirm its clinical utility.},
}
@article {pmid41282784,
year = {2025},
author = {Zhang, PW and Wan, ZH and Liu, S and Wang, J and Sripathi, S and Li, W and Ahn, J and Li, S and Fan, L and Berlinicke, CA and Qian, J and Merbs, SL and Zack, DJ},
title = {HTRA1-AS1 , an ARMS2 -region long non-coding RNA, is downregulated in retinas of age-related macular degeneration patients.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282784},
abstract = {PURPOSE: The human 10q26 locus is a major genetic risk factor for age-related macular degeneration (AMD). Fine mapping by linkage and large-scale genome-wide association studies (GWAS) has narrowed this region to a 30-kb interval encompassing the ARMS2 and HTRA1 genes. However, the causative gene(s), risk variants, and underlying pathogenic mechanisms remain unresolved.<br><br>METHODS: Long non-coding RNA (lncRNA) candidates within the ARMS2-HTRA1 region were identified using human postmortem retinal RNA-seq data and public databases (NCBI, Ensembl). Candidate transcripts were validated by RT-PCR and Sanger sequencing. Published single-cell RNA-seq datasets were analysed to define cell type-specific expression, and RNA levels were compared between AMD and non-AMD donor retinas. Additionally, expression changes were assessed in human iPSC-derived retinal pigment epithelium (RPE) cells exposed to cigarette smoke extract (CSE) and paraquat (PQT).<br><br>RESULTS: We identified and validated a lncRNA, HTRA1-AS1 , and its transcript variants (ENST00000647969.1) within the ARMS2 locus. HTRA1-AS1 overlaps ARMS2 and is transcribed in the antisense orientation. It is predominantly expressed in rod photoreceptors, M&#xfc;ller glia and Choroid/RPE, and its retinal expression was significantly reduced in AMD compared with controls (43 AMD donors vs. 44 controls, p = 0.007). By contrast, HTRA1 mRNA showed no significant difference (p = 0.121). Furthermore, ENST00000647969.1, HTRA1-AS1 and ARMS2 expression increased dramatically, up to 101-fold, 8-fold and 75-fold, respectively, in induced pluripotent stem cells (iPSC)-derived RPE cells following cigarette smoke extract (CSE)-induced oxidative stress but showed no significant change after paraquat treatment.<br><br>CONCLUSION: These findings suggest that HTRA1-AS1 , a dysregulated lncRNA within the ARMS2 locus, may act as a non-coding element contributing to transcriptional mis-regulation underlying AMD pathogenesis.},
}
@article {pmid41282676,
year = {2025},
author = {Banijamali, SMA and Versek, C and Lashkari, K and Bex, P and Sridhar, S},
title = {Mobile Objective Diagnostics of Macular Degeneration using Dark-Adapted Visual Evoked Potentials.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282676},
abstract = {PURPOSE: Delayed Dark-Adapted vision Recovery (DAR) is a known biomarker for Age-related Macular Degeneration (AMD); however, its measurement is often cumbersome for both patients and examiners. In this study, we developed NeuroVEP, a portable, wireless, and user-friendly system designed to objectively assess Dark-Adapted Visual Evoked Potentials (DAVEP).<br><br>METHODS: NeuroVEP consists of a headset with a smartphone that delivers controlled photo-bleach and monocular pattern reversal stimuli while utilizing custom electroencephalography (EEG) electrodes and electronics to measure DAVEP. The system allows for separate analysis of the near peripheral and macular visual field of each eye, completing the test in a comfortable, single-session format (<25 minutes) without requiring subjective patient feedback.The NeuroVEP test protocol included: (i) Mesopic luminance pattern reversal VEP for macular and peripheral regions (5 mins), (ii) Full-field photopic pattern reversal VEP (2.5 mins), (iii) Scotopic luminance DAVEP recovery post photo-bleach (up to 15 mins), measured simultaneously from both eyes.The data were analyzed for 66 participants, divided into four cohorts: (A) Age-matched healthy controls with no ophthalmic pathologies (n=10), (B) Early-stage AMD (AREDS1) (n=19), (C) Intermediate-stage AMD (AREDS3) (n=18), (D) Advanced-stage AMD (AREDS4/5) (n=19).Advanced signal processing and machine learning methodologies were applied to filter and process the VEP responses from the DAR segment of the experiment. 13 discriminating features were extracted from the processed signals and classified for each participant using a Bayesian statistical framework and Gaussian Mixture Model (GMM).<br><br>RESULTS: The algorithm demonstrated: 86% accuracy in early-stage AMD detection (Healthy vs. Early AMD) (Sensitivity: 97%, Specificity: 65%, AUC-ROC: 0.81 and AUC-PR: 0.92) and 93% accuracy in overall AMD detection (Healthy vs. All AMD stages) (Sensitivity: 98%, Specificity: 65%, AUC-ROC: 0.82 and AUC-PR: 0.97).<br><br>CONCLUSIONS: We successfully developed a portable, objective user-friendly VEP system and an advanced Bayesian-GMM statistical analysis framework capable of identifying DAR deficits in AMD patients. This novel technology shows high potential for early AMD detection and could serve as a non-invasive, objective diagnostic tool for AMD screening in clinical and remote settings.},
}
@article {pmid41282061,
year = {2025},
author = {Lizińczyk, AM and Pankiewicz, JE and Cullina, WL and Franco, LA and Sullivan, PM and Sadowski, MJ},
title = {APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7820890/v1},
pmid = {41282061},
issn = {2693-5015},
abstract = {APOE polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer's disease, primary tauopathies, α-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using APOE targeted replacement (TR) mice, we investigated how APOE genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female ε2/ε2 , ε3/ε3 , and ε4/ε4 APOE -TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. ε4/ε4 22L mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. ε2/ε2 22L mice performed significantly better than ε4/ε4 22L mice but significantly worse than ε3/ε3 22L animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the ε4 allele including increased PrP [Sc] accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between ε2/ε2 22L and ε3/ε3 22L mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in ε4/ε4 22L mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in ε4/ε4 22L mice. ε4/ε4 22L mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by ε2/ε2 22L , with ε3/ε3 22L having the lowest. Thus, APOE polymorphism differentially regulates the progression of prion pathology attributable to two ε4 -affected mechanisms: increased conversion and accumulation of PrP [Sc] and worsened prion-associated neuroinflammation. Though less severely than ε4 , the ε2 allele also increased the inflammatory response, rendering disease outcome worse relative to the ε3 allele. Our findings suggest both ε4 and ε2 alleles are disadvantageous determinants in prion pathology.},
}
@article {pmid41281747,
year = {2025},
author = {Yang, B and Yang, K and Chen, Y and Xi, R and Han, J and Li, S and Chen, J and Wu, Y},
title = {Activation of GSDME by all-trans-retinal increases sensitivity to photoreceptor ferroptosis.},
journal = {International journal of biological sciences},
volume = {21},
number = {15},
pages = {7029-7042},
pmid = {41281747},
issn = {1449-2288},
mesh = {Animals ; *Ferroptosis/physiology/drug effects/genetics ; Mice ; Mice, Knockout ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; *Photoreceptor Cells, Vertebrate/metabolism ; *Retinaldehyde/metabolism/pharmacology ; Mice, Inbred C57BL ; Lipid Peroxidation ; Mitochondria/metabolism ; Retinal Degeneration/metabolism ; Macular Degeneration/metabolism ; ATP-Binding Cassette Transporters ; },
abstract = {Impaired clearance of all-trans-retinal (atRAL) due to visual cycle dysfunction contributes to photoreceptor atrophy, a key pathological hallmark of Stargardt disease type 1 (STGD1) and dry age-related macular degeneration (AMD). Prior studies have shown that light-induced atRAL accumulation promotes ferroptosis and activates gasdermin E (GSDME) in retinal photoreceptors of Abca4[-/-]Rdh8[-/-] mice, a model for STGD1 and dry AMD that exhibits visual cycle disorders. However, the role of GSDME in photoreceptor ferroptosis remains unclear. In this study, we revealed that GSDME activation by atRAL triggered photoreceptor ferroptosis and retinal atrophy via mitochondrial damage and oxidative stress. Knocking out GSDME significantly attenuated light-induced photoreceptor ferroptosis and retinal degeneration in Abca4[-/-]Rdh8[-/-] mice. Moreover, deleting the Gsdme gene in photoreceptor cells prevented atRAL-induced ferroptosis by inhibiting mitochondrial reactive oxygen species (mitoROS) production, iron overload, and lipid peroxidation. Notably, treatment with the mitoROS scavenger MitoTEMPO mitigated ferroptosis in atRAL-loaded photoreceptor cells and dramatically relieved photoreceptor ferroptosis and retinal degeneration in light-exposed Abca4[-/-]Rdh8[-/-] mice. We found that both GSDME elimination and MitoTEMPO treatment repressed atRAL-induced photoreceptor ferroptosis and retinal atrophy by inactivating the mitoROS-induced oxidative stress. In conclusion, GSDME-mediated photoreceptor ferroptosis is crucial for inducing structural and functional damage of the retina in retinopathies caused by atRAL accumulation, thereby providing new therapeutic insights for the prevention and treatment of STGD1 and dry AMD.},
}
@article {pmid41280070,
year = {2025},
author = {Shin, K and Brown, W and Tian, Y and Gopinath, T and Bobkov, AA and Marinelli, F and Marassi, FM},
title = {Structural basis for lipid binding by the blood protein vitronectin, a component of HDL.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.01.685992},
pmid = {41280070},
issn = {2692-8205},
abstract = {Vitronectin (Vn) is a multifunctional blood glycoprotein involved in cell adhesion and migration, blood coagulation, and inflammation. It is a component of the high-density lipoprotein (HDL) proteome, and often found associated with the calcified, lipid-rich, protein deposits that are a hallmark of age-related macular degeneration, Alzheimer's disease, atherosclerosis and other aging-related diseases. Here we explored the molecular basis for lipid binding by Vn using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and all-atom molecular dynamics (MD) simulations. The data reveal a hydrophobic groove on the surface of the hemopexin-like (HX) domain of Vn, that is capable of binding phosphatidylcholine (PC). Conformational landscape analyses of multiple, independent MD simulations identify key structural motifs and intermolecular contacts mediating the association of Vn with PC, and show that lipid binding is guided by interactions with positively charged and hydrophobic residues that organize the lipids in a tail-to-tail bilayer-like arrangement within the groove. Collectively, the data establish a comprehensive structural model for Vn association with HDL and provide mechanistic insight into its accumulation within lipid-rich deposits characteristic of age-related pathologies.},
}
@article {pmid41279388,
year = {2025},
author = {Maniglia, M and Vice, J and Maxwell, E and Visscher, KM and Seitz, AR},
title = {Examining oculomotor behavior in central vision loss with a gaze-contingent display.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279388},
issn = {2692-8205},
support = {R21 EY033623/EY/NEI NIH HHS/United States ; },
abstract = {Patients with central vision loss due to macular degeneration (MD) must rely on their peripheral vision for tasks normally performed by the fovea. Many patients develop a preferred retinal locus (PRL), an eccentric retinal location used as a substitute for the damaged fovea in tasks such as face recognition, navigation, and reading. However, the mechanisms underlying PRL development remain elusive, and no single hypothesis fully explains its characteristics. Investigations into PRL development are hindered by oculomotor assessments, which often focus on fixation ability while neglecting other eye movement characteristics and potentially conflating different behaviors over time. In previous work, we introduced a series of oculomotor metrics in cases of simulated central vision loss, demonstrating that complex profiles of eye movement behavior can be extracted from a simple visual task. Here we present longitudinal data from 10 patients with MD as evidence of the feasibility of using these metrics to characterize different profiles of eye movements following central vision loss. Consistent with findings in healthy individuals using artificial scotoma, the metrics reveal substantial individual differences in behavior, both at baseline and after visual training. Overall, patients exhibit significantly higher saccadic re-referencing than controls, despite larger inter-individual differences. These metrics provide a detailed evaluation of oculomotor behavior in patients with central vision loss and offer a valuable tool for assessing progress in training protocols.},
}
@article {pmid41279129,
year = {2025},
author = {Zhang, PW and Liu, S and Li, W and Fan, L and Li, S and Wan, ZH and Berlinicke, CA and Merbs, SL and Zack, DJ},
title = {Identification and functional characterization of an AMD associated c-ABL binding SNP streak within the ARMS2 gene promoter region.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.27.684937},
pmid = {41279129},
issn = {2692-8205},
abstract = {BACKGROUND: Large-scale genome-wide association studies (GWAS) have identified the human 10q26 locus as a major genetic risk factor for age-related macular degeneration (AMD). The AMD-associated interval has been refined to a 5,196 bp segment flanking the ARMS2-HTRA1 region, excluding HTRA1 and the ARMS2 3' indel (443del54ins) variant by risk haplotype analysis. Although the missense SNP rs10490924 has been proposed as a functional variant, its role in AMD remains controversial, and the causative variants and underlying mechanisms within this region remain unresolved.<br><br>METHODS: An unbiased bioinformatic screen identified a 5-SNP block within the 5,196 bp interval that potentially alters c-ABL protein binding. Protein-DNA interactions were validated using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Genetic association with AMD (dry and wet subtypes) was assessed in patient cohorts using blood genomic DNA. The regulatory effect of the 5-SNP block was further examined using luciferase reporter assays.<br><br>FINDINGS: We identified a 5-SNP block located &#x223c;556 bp upstream of the ARMS2 start codon, representing a cluster of predicted c-ABL tyrosine kinase binding sites. This block, in complete linkage disequilibrium with rs10490924 (A69S), showed a strong association with both wet and dry AMD (136 controls, 179 dry AMD, 251 wet AMD). EMSA and ChIP confirmed direct c-ABL binding, while luciferase reporter assays demonstrated reduced transcriptional activity mediated by the 5-SNP block in the presence of c-ABL.<br><br>INTERPRETATION: Our results suggest that the c-ABL-responsive 5-SNP regulatory streak in the ARMS2 promoter region act as functional non-coding elements that may contribute to AMD pathogenesis through altered transcriptional regulation.},
}
@article {pmid41278837,
year = {2025},
author = {Oshima, Y and Hussey, KA and Hagen, J and Smit-McBride, Z and Moorthy, M and Matsubara, JA and Flajnik, M and Johnston, RJ and Vogel, BE},
title = {Complement Factor H and its C. elegans homolog regulate IFT52/OSM-6 and CNG channel localization in sensory neurons.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41278837},
issn = {2692-8205},
support = {P30 EY012576/EY/NEI NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Current disease models propose AMD pathogenesis is a consequence of cytolytic damage and tissue inflammation that result from defective repression of alternative complement pathway activity by complement factor H (CFH). However, recent studies demonstrate functions for CFH that are outside of its established role in the alternative complement pathway, suggesting that novel CFH-mediated mechanisms may influence AMD initiation and progression. Our previous demonstration that CFH and its nematode homolog, CFH-1, modulate inversin/NPHP-2 accumulation in vertebrate photoreceptor and C. elegans sensory neuron cilia during aging suggests that AMD patients with CFH loss-of-function mutations have cilia defects that may contribute to photoreceptor dysfunction. Here, we investigate the consequences of CFH and CFH-1 loss-of-function mutations on the dynamics and localization of intraflagellar transport (IFT) train and visual cycle components in these cells. In C. elegans sensory neurons, IFTB1 components IFT52/OSM-6 and IFT88/OSM-5 are transported at similar rates in WT animals but IFT52/OSM-6 transport slows significantly in cfh-1 mutant animals while IFT88/OSM-5 is unaffected. Defective localization of IFT52/OSM-6 in photoreceptors of CFH knockout mice and in human photoreceptors from AMD high-risk CFH Y402H homozygotes, suggest an evolutionarily conserved role for CFH in promoting IFT52/OSM-6 transport and localization in sensory neuron cilia. In addition, distribution of CNG channel subunits in C. elegans cfh-1 mutant sensory neurons and CFH Y402H high-risk human photoreceptors are distinct from their WT and Y402 low-risk counterparts. Together, the data indicate previously unappreciated functions for CFH in IFT train organization and cilia protein localization and suggest a novel mechanism for photoreceptor segment thinning, an early AMD biomarker that has been linked to CFH high-risk variants.},
}
@article {pmid41278702,
year = {2025},
author = {Oshima, Y and Nagidi, Y and Moorthy, ME and Heier, J and Matsubara, JA and Hardin, J and Flajnik, M and Vogel, BE},
title = {TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41278702},
issn = {2692-8205},
support = {P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and C. elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for non-canonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.},
}
@article {pmid41277047,
year = {2025},
author = {Choe, S and Ye, J and Zhang, T and Gao, J},
title = {Advanced Drug Delivery Systems for Age-Related Macular Degeneration Treatment: Latest Trends and Future Prospects.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e03757},
doi = {10.1002/adhm.202503757},
pmid = {41277047},
issn = {2192-2659},
support = {W2442037//National Natural Science Foundation of China/ ; 2023GSP006851//Chinese Government Scholarship/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. While wet AMD is primarily characterized by choroidal neovascularization, dry AMD is characterized by dysfunction of the retinal pigment epithelium. One of the key challenges in AMD treatment is achieving efficient drug delivery to the posterior segment, a task complicated by the anatomical and physiological barriers, such as rapid clearance from the vitreous. Current therapeutic approaches, mainly constituted by frequent intravitreal injections of anti-vascular endothelial growth factor agents for wet AMD, place a heavy burden on patients, leading to complications such as retinal detachment and endophthalmitis. This review highlights recently developed drug delivery systems designed to overcome these challenges and the potential of these systems to transform AMD management. These systems include hydrogels, nanocarriers, and biologically derived vesicles, which enable sustained, localized drug release and improved targeting. Additionally, device-based delivery systems such as microneedles, ultrasound-mediated systems, magnetically guided systems, 3D bioprinting, and implantable sustained-release devices are explored for their potential to reduce injection frequency and improve therapeutic outcomes. Lastly, it outlines future efforts needed to accelerate the clinical adoption of these innovative therapies, with a focus on patient safety, efficacy, and quality of life in AMD treatment.},
}
@article {pmid41276957,
year = {2025},
author = {Yang, CC and Weng, CC and Chou, YB and Huang, YM and Lin, TC and Chen, SJ and Hwang, DK},
title = {Early anatomical outcomes of faricimab vs. aflibercept 2 mg in treatment-naïve neovascular AMD and PCV: A head-to-head comparative study in Taiwan.},
journal = {Journal of the Chinese Medical Association : JCMA},
volume = {},
number = {},
pages = {},
doi = {10.1097/JCMA.0000000000001320},
pmid = {41276957},
issn = {1728-7731},
abstract = {BACKGROUND: While clinical trials have established the non-inferiority of faricimab compared to aflibercept regarding 1-year visual acuity, real-world evidence directly comparing their early effects on anatomical changes remains limited. This study aimed to compare the early effects of these treatments in treatment-naïve Asian patients with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This retrospective study included treatment-naive nAMD patients who received three monthly intravitreal injections of 6.0 mg/0.05 mL faricimab or 2.0 mg/0.05 mL aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HRF), and subretinal hyperreflective material (SHRM) were assessed monthly for 4 months.<br><br>RESULTS: A total of 76 eyes of 76 patients (38 per group) were enrolled in this study. Baseline characteristics were comparable between the two groups, and there were no significant differences in BCVA, CMT, SFCT, SRF and IRF at 4 months (p > 0.05). However, the faricimab group had significant improvements in BCVA at months 2, 3, and 4 (p < 0.05), while this was not seen in the aflibercept group. The decrease in mean logarithm of the minimum angle of resolution (logMAR) was from 0.78 &#xb1; 0.47 to 0.66 &#xb1; 0.65 in the faricimab group compared to 0.78 &#xb1; 0.41 to 0.72 &#xb1; 0.60 in the aflibercept group (p = 0.348) at 4 months. Moreover, significantly fewer faricimab-treated patients had PED (67.6% vs. 91.9%, p = 0.016), SHRM (32.4% vs. 59.5%, p = 0.022), and HRF (52.9% vs. 89.2%, p = 0.001) at 4 months.<br><br>CONCLUSION: Faricimab and aflibercept demonstrated comparable effects on BCVA, CMT, and SFCT. However, faricimab was associated with better early control of PED, SHRM, and HRF. Further prospective trials are needed to validate our findings.},
}
@article {pmid41275318,
year = {2025},
author = {Lim, J and Cho, H and Ramkumar, H and Adrean, SD},
title = {Neovascular age-related macular degeneration complicated by large submacular hemorrhage managed with faricimab monotherapy.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00771-5},
pmid = {41275318},
issn = {2056-9920},
}
@article {pmid41273407,
year = {2025},
author = {Ferreira, AM and Vilares-Morgado, R and Martins, L and Marques-Couto, P and Rocha-Sousa, A and Carneiro, &#xc2; and Falcão, M},
title = {Non-exudative macular neovascularization: a 3-year follow-up study assessing the progression for exudative or atrophic stages.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41273407},
issn = {1435-702X},
abstract = {INTRODUCTION: Non-exudative macular neovascularization (NE-MNV) has been linked to smaller areas of geographic atrophy (GA), suggesting it may slow the progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA). This study aims to determine whether NE-MNV affects the prevalence and progression to later stages of age-related macular degeneration (AMD) over 3 years in the fellow eyes of patients with unilateral exudative AMD.<br><br>METHODS: Observational study including 61 patients with unilateral exudative AMD assessing 3-year cRORA progression and exudative conversion in the fellow eye. Patients were grouped based on the presence (NE-MNV) or absence of NE-MNV (no NE-MNV). The prevalence and progression of tomographic cRORA, GA on fundus autofluorescence (FAF) and exudative conversion rates were compared.<br><br>RESULTS: Sixty-one patients were included in our cohort. The prevalence of NE-MNV was 24.6%. We identified a 36.3% bilateral exudative conversion rate (n&#x2009;=&#x2009;4) in the NE-MNV group and a 15.2% conversion rate in the eyes without NE-MNV (n&#x2009;=&#x2009;7) at 3 years (p&#x2009;=&#x2009;0.036). There were no significant differences in cRORA or FAF GA prevalence between groups (2/15 (13.3%) with NE-MNV vs. 11/35 (31.4%) without NE-MNV, p&#x2009;=&#x2009;0.410). Eyes with NE-MNV presented a significantly smaller cRORA greatest linear diameter (GLD) than eyes without NE-MNV (1342.3&#x2009;&#xb1;&#x2009;1260 vs. 2897&#x2009;&#xb1;&#x2009;1925.3, p&#x2009;=&#x2009;0.023), and a smaller FAF GA area (4.5&#x2009;&#xb1;&#x2009;3.7 vs. 11.9&#x2009;&#xb1;&#x2009;10.6 mm2, p&#x2009;=&#x2009;0.042). The presence of reticular pseudodrusen and hypertransmission defects were significantly associated with the GA phenotype (p&#x2009;=&#x2009;0.002 and p&#x2009;<&#x2009;0.001, respectively) while the identification of concurrent large drusen was significantly associated with the presence of MNV, both exudative and non-exudative (p&#x2009;=&#x2009;0.023). The increase in OCTA NE-MNV area and the presence of anastomosis and loops pattern were associated with exudative conversion (p&#x2009;=&#x2009;0.046 and p&#x2009;=&#x2009;0.032, respectively).<br><br>CONCLUSION: The presence of NE-MNV was associated with smaller cRORA GLD and FAF GA area, corroborating that NE-MNV may prevent the progression of cRORA. One third of the eyes with NE-MNV converted to exudative AMD over 3-years. Reticular pseudodrusen, hypertransmission defects and concurrent large drusen were significant OCT biomarkers for late stages AMD. Extended monitoring is required to confirm these results at long term.},
}
@article {pmid41272236,
year = {2025},
author = {Pidishetty, D and Damera, SK and Murugavel, M and Susaimanickam, PJ and Chittajallu, SNSH and Kushawah, G and Sarkar, P and Bharadwaj, SR and Mishra, R and Mariappan, I},
title = {Loss of retinal stem cell reserve and lipofuscin accumulation accelerates cone-rod degeneration and replicates Stargardt disease in abca4b null zebrafish.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-28951-1},
pmid = {41272236},
issn = {2045-2322},
abstract = {Mutations in ABCA4 gene causes Stargardt macular degeneration, which manifests with toxic lipofuscin deposits in the outer retina, gradual atrophy of RPE cells, followed by photoreceptor cell loss. The cone-enriched retina, with macula-like 'area-temporalis' of zebrafish are better models than rodents for studying human macular dystrophies. Here, we generated abca4b knockout zebrafish model using CRISPR/Cas9 editing and evaluated the early and late-stage retinal changes. In adult abca4b[-/-] mutants, the RPE cells exhibited hyperpigmentation, altered retinomotor behaviour and lipofuscin accumulation, but they remained viable. However, the photoreceptors underwent progressive degeneration, with a sequential loss of blue and UV cones, followed by red and green cones and finally the rod cells. This triggered the chronic activation and early depletion of retinal stem cells at the ciliary marginal zone of mutants and resulted in accelerated outer-retinal degeneration and severe visual defects, despite them retaining the Müller glia-dependant retinal repair potential.},
}
@article {pmid41271910,
year = {2025},
author = {Tabuchi, H and Nagasato, D and Tanabe, M and Murata, K and Ishitobi, N and Kato, D and Kazunori, A},
title = {Evaluation of deep learning-based retinal pigment epithelium segmentation for a widely used optical coherence tomography device.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {41310},
pmid = {41271910},
issn = {2045-2322},
mesh = {Humans ; *Tomography, Optical Coherence/methods/instrumentation ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; *Deep Learning ; Algorithms ; Aged ; Macular Degeneration/diagnostic imaging ; Male ; Female ; Diabetic Retinopathy/diagnostic imaging ; Middle Aged ; *Image Processing, Computer-Assisted/methods ; },
abstract = {To develop our proposed technology method to improve retinal pigment epithelium (RPE) detection in optical coherence tomography (OCT) images and compare its efficacy with Topcon's automated segmentation algorithm across multiple retinal diseases and healthy eyes. OCT images from 88 patients with age-related macular degeneration (AMD) were used for our proposed technology model training and validation. For testing with separate images were obtained from patients with AMD (100), diabetic retinopathy (DR; 50), epiretinal membrane (ERM; 50), branch retinal vein occlusion (BRVO; 50), and healthy eyes (50). The proposed technology was used to identify RPE in OCT images using the Pyramid Scene Parsing Network on top of ResNet-50. The accuracy of the proposed technology method in RPE detection was measured using the mean absolute error (MAE) and compared with Topcon's automated segmentation algorithm for each retinal condition. As compared with Topcon's automated segmentation algorithm, the proposed technology showed significantly better MAEs across all conditions: AMD (2.18 vs. 4.79), DR (1.69 vs. 3.17), ERM (1.50 vs. 2.67), BRVO (1.86 vs. 2.98), and healthy eyes (1.59 vs. 2.28). Notably, the proposed technology's superiority was most evident in the AMD group. The proposed technology method outperformed Topcon's automated segmentation algorithm in accurately visualizing RPE in OCT images across all tested conditions, especially in AMD. Our results indicate the proposed technology's potential to elevate the RPE segmentation which can lead to enhancing ophthalmology care by providing more accurate OCT imaging analyses.},
}
@article {pmid41270813,
year = {2025},
author = {Jiang, L and Xu, Z and Ma, J and Cai, W and Lin, R and Hu, C and Luo, Y and Liang, F and Wu, Y and Yu, J},
title = {siRASA1 in vascular endothelial cells alleviates subretinal fibrosis through inhibiting macrophage-myofibroblast transdifferentiation via SHH signaling pathway.},
journal = {Cellular signalling},
volume = {138},
number = {},
pages = {112261},
doi = {10.1016/j.cellsig.2025.112261},
pmid = {41270813},
issn = {1873-3913},
abstract = {Subretinal fibrosis (SRF) is a vision-threatening complication of neovascular age-related macular degeneration (nAMD) driven by angiogenesis, inflammation, and collagen deposition，which is refractory to current anti-VEGF treatments. This study investigates the role of RASA1 in promoting SRF through Sonic Hedgehog (SHH) signaling. We found that VEGF stimulation upregulates RASA1 in human umbilical vein endothelial cells (HUVECs), potentiating the secretion of SHH. Secreted SHH then activates the SHH-SMO/PTCH1-GLI1 axis in macrophages, driving their transdifferentiation into myofibroblasts and promoting fibrogenesis. Furthermore, a positive feedback loop was identified: macrophage-derived EFNB2 activated EphB4-RASA1 in HUVECs, exacerbating fibrosis. To therapeutically disrupt this circuit, we engineered a multifunctional nanoparticle system, MGPDA@Eylea/siRASA1, for the co-delivery of siRASA1 and the anti-VEGF drug Eylea. This nanotherapeutic demonstrated excellent biocompatibility and effectively attenuated the fibrotic cascade by suppressing RASA1 expression, inhibiting SHH signaling, and mitigating macrophage-to-myofibroblast transition (MMT), thereby delaying SRF progression. Our work unveils a previously unrecognized intercellular circuit driving fibrosis and presents a promising nanomedicine-based strategy for managing fibrotic complications in nAMD.},
}
@article {pmid41270236,
year = {2025},
author = {Shi, N and Li, J and Shang, M and Zhang, W and Xu, K and Li, Y and Liang, L},
title = {Detection and Management of Geographic Atrophy Secondary to Age-Related Macular Degeneration Using Noninvasive Retinal Images and Artificial Intelligence: Systematic Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e81328},
pmid = {41270236},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Deep Learning ; *Geographic Atrophy/diagnostic imaging/etiology/diagnosis/therapy ; *Macular Degeneration/complications/diagnostic imaging ; *Retina/diagnostic imaging ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: Geographic atrophy (GA), the endpoint of dry age-related macular degeneration (AMD), is irreversible. The recent approval by the Food and Drug Administration of a complement component 3 inhibitor marks a significant breakthrough, highlighting the critical importance of early detection and management of GA. Consequently, there is an urgent and unmet need for efficient, accurate, and accessible methods to identify and monitor GA. Artificial intelligence (AI), particularly deep learning (DL), applied to noninvasive retinal imaging, offers a promising solution for automating and enhancing GA management.<br><br>OBJECTIVE: This systematic review aimed to assess the performance of AI using noninvasive imaging modalities and compare it with clinical expert assessment as the ground truth.<br><br>METHODS: Two consecutive searches were conducted on PubMed, Embase, Web of Science, Scopus, Cochrane Library, and CINAHL. The last search was performed on October 5, 2025. Studies using AI for GA secondary to dry AMD via noninvasive retinal imaging were included. Two authors worked in pairs to extract the study characteristics independently. A third author adjudicated disagreements. Quality Assessment of Diagnostic Accuracy Studies-AI and Prediction Model Risk of Bias Assessment Tool (PROBAST) were applied to evaluate the risk of bias and application.<br><br>RESULTS: Of the 803 records initially identified, 176 were found through an updated search. Subsequently, 200 papers were assessed in full text, of which 41 were included in the final analysis, 10 for GA detection, 20 for GA assessment and progression, and 11 for GA lesion prediction. The reviewed studies collectively involved at least 24,592 participants (detection: n=7132, assessment and progression: n=14,064, and prediction: n=6706), with a wide age range of 50 to 94 years. The studies spanned a diverse array of countries, including the United States, the United Kingdom, China, Austria, Australia, France, Israel, Italy, Switzerland, and Germany, as well as a multicenter study encompassing 7 European nations. The studies used a variety of imaging modalities to assess GA, including color fundus photography, fundus autofluorescence, near-infrared reflectance, spectral domain-optical coherence tomography (OCT), swept-source (SS)-OCT, and 3D-OCT. DL algorithms (eg, U-Net, ResNet50, EfficientNetB4, Xception, Inception v3, and PSC-UNet) consistently showed remarkable performance in GA detection and management tasks, with several studies achieving performance comparable to clinical experts.<br><br>CONCLUSIONS: AI, particularly DL-based algorithms, holds considerable promise for the detection and management of GA secondary to dry AMD with performance comparable to ophthalmologists. This review innovatively consolidates evidence across GA management-from initial detection to progression prediction-using diverse noninvasive imaging. It has strong potential to augment clinical decision-making. However, to realize this potential in real-world settings, future research is needed to robustly enhance reporting specifications, ensure data diversity across populations and devices, and implement rigorous external validation in prospective, multicenter studies.},
}
@article {pmid41269906,
year = {2025},
author = {Korobelnik, JF and Chaudhary, V and Mitchell, P and Kang, SW and Allmeier, H and Lee, J and Zhang, X and Machewitz, T and Bailey, C},
title = {Aflibercept 2 mg for Neovascular Age-Related Macular Degeneration: XTEND at 3 Years.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1-21},
doi = {10.1159/000549663},
pmid = {41269906},
issn = {1423-0267},
abstract = {INTRODUCTION: Long-term, global, data evaluating intravitreal aflibercept (IVT-AFL) 2 mg for treatment of neovascular age-related macular degeneration (nAMD) in real-world practice are needed. This study investigated the long-term, real-world effectiveness and safety of IVT-AFL 2 mg in patients with nAMD.<br><br>METHODS: XTEND was a multicenter, observational, prospective study. Enrollment was conducted between May 2019 and May 2020; patient follow-up period was 36 months. Treatment-na&#xef;ve patients were treated with IVT-AFL 2 mg (fixed dosing or treat-and-extend [T&amp;E]) according to the local label; for the T&amp;E regimen, treatment intervals could be extended according to the national label (either European Medicines Agency [EMA]-aligned or non-EMA-aligned).<br><br>RESULTS: Overall, 1483 patients across 17 countries were treated with IVT-AFL 2 mg; mean &#xb1; standard deviation (SD) age was 78.8 &#xb1; 8.5 years; 60.4% were female. Overall, 62.6% of patients completed the 36-month follow-up visit. The mean (95% confidence interval [CI]) changes in best-corrected visual acuity from baseline were +4.6 (3.7, 5.4), +2.3 (1.3, 3.3), and +0.9 (-0.2, 1.9) at Months 12, 24, and 36, respectively. The mean (95% CI) changes in central subfield thickness from baseline were -106 (-114, -99) &#x3bc;m, -109 (-117, -102) &#x3bc;m, and -110 (-118, -103) &#x3bc;m at Months 12, 24, and 36, respectively. The mean &#xb1; SD numbers of injections from baseline to Months 12, 24, and 36 were 7.7 &#xb1; 2.7, 11.3 &#xb1; 5.3, and 13.7 &#xb1; 7.5, respectively. No new safety concerns were identified.<br><br>CONCLUSION: This study demonstrates that improvements with IVT-AFL 2 mg were maintained through Month 36, suggesting that long-term durability of vision is achievable in patients with treatment-na&#xef;ve nAMD in real-world practice.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03939767. Available at: https://www.<br><br>CLINICALTRIALS: gov/study/NCT03939767.},
}
@article {pmid41269403,
year = {2025},
author = {Jin, J and Hand, R and Meltzer, M and Abate, C and Geva, M and Hayden, MR and Ross, CA},
title = {Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {121},
pmid = {41269403},
issn = {1559-1182},
mesh = {*Receptors, sigma/antagonists &amp; inhibitors/agonists/metabolism ; *Huntington Disease/drug therapy/pathology/metabolism ; Animals ; *Neuroprotective Agents/pharmacology/therapeutic use ; Sigma-1 Receptor ; *Piperidines/pharmacology/therapeutic use ; Mice ; Humans ; Neurons/drug effects/metabolism/pathology ; Huntingtin Protein/metabolism ; },
abstract = {Pridopidine is a selective sigma-1 receptor (S1R) agonist in clinical development for Huntington's Disease (HD) and Amyotrophic Lateral Sclerosis (ALS). Activation of the S1R by pridopidine is neuroprotective in multiple preclinical models of neurodegenerative disease. The sigma-2 receptor (S2R) is evolutionarily and structurally unique from the S1R. Nevertheless, the S1R and S2R share an overlapping yet distinct ligand binding profile. Inhibition of the S2R is neuroprotective and S2R antagonists are in clinical development for Alzheimer's Disease (AD), ⍺-synucleinopathies, and dry age-related macular degeneration. In this study, we hypothesized that simultaneous activation of the S1R by pridopidine and inhibition of the S2R by the selective S2R antagonist FA10 might provide enhanced protection against mutant huntingtin (mHTT) expression in an in vitro model of neurodegeneration. Consistent with previous studies, pridopidine reduced neuronal cell death in a mouse primary neuron mHTT model. Similarly, we found that inhibition of the S2R by FA10 was also sufficient to protect against mHTT induced neurodegeneration in this model. The combination treatment of pridopidine and FA10 achieved greater efficacy than either compound alone, even at lower concentrations. The combination of these compounds may allow for lower efficacious doses leading to improved safety profiles and reduced off-target effects. This novel combinatorial approach, in which the S1R is activated while simultaneously inhibiting the S2R may prove to be a highly effective therapeutic strategy for HD and other neurodegenerative diseases.},
}
@article {pmid41268988,
year = {2025},
author = {Kozak, I and Sinclair, SH and Zhang, E and Murati, F and Lee, E and Stepura, A and Dey, A and Ribaric, N},
title = {Application of Deep Learning for Advanced Detection and Quantification of Drusen in Nonexudative AMD From Retinal Multispectral Imaging.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {11},
pages = {35},
pmid = {41268988},
issn = {2164-2591},
mesh = {*Deep Learning ; Humans ; *Retinal Drusen/diagnosis/diagnostic imaging ; *Macular Degeneration/diagnosis ; *Retina/diagnostic imaging/pathology ; Neural Networks, Computer ; Aged ; *Geographic Atrophy/diagnosis ; },
abstract = {PURPOSE: To propose a novel deep learning-based methodology for drusen detection and quantification in early age-related macular degeneration (AMD) using retinal multispectral images. The retinal multispectral images highlight features in several nonoverlapping spectral bands that the deep learning models leverage for automatic drusen detection and quantification in dry AMD.<br><br>METHODS: The proposed novel methodology comprises quality assessment of retinal images, region of interest extraction, drusen segmentation, and drusen quantification stages. Different deep learning models (such as UNet++ convolutional neural network with EfficientNetV2 encoder) have been implemented for these stages. A total of 170 drusen and 150 nondrusen retinal images (single eye) were split into four training and validation data sets to analyze the performance of a deep learning model for drusen segmentation.<br><br>RESULTS: The proposed methodology achieved an average score, recall, and precision of 0.691, 0.668, and 0.776, respectively, across all four validation sets. This work also analyzed the performance of the proposed deep learning model for discriminating drusen and drusen-like lesions, achieving a pixel-wise segmentation accuracy of 99.998%. The number and the diameter of the detected drusen were also computed. A Dice score distribution for drusen segmentation with different numbers and sizes of drusen per eye is also shown.<br><br>CONCLUSIONS: This work demonstrates that deep learning models applied to retinal multispectral images can provide accurate and clinically significant drusen segmentation and quantification, thereby facilitating early detection, longitudinal monitoring, and reduction of the risk of vision loss from AMD.<br><br>TRANSLATIONAL RELEVANCE: Deep learning-assisted detection of drusen from multispectral retinal images will refine and improve clinical diagnosis of early nonexudative age-related macular degeneration.},
}
@article {pmid41268217,
year = {2025},
author = {Amer, M and Sonne, S and Piri, N},
title = {Hyperreflective Choroidal Foci: A Comprehensive Review.},
journal = {Journal of ophthalmic &amp; vision research},
volume = {20},
number = {},
pages = {},
pmid = {41268217},
issn = {2008-2010},
abstract = {Hyperreflective choroidal foci (HCF) are a finding on optical coherence tomography that may serve as a biomarker in various retinal and choroidal pathologies. These discrete hyperreflective spots, identified in various layers of the choroid, have been linked to inflammatory, vascular, and degenerative conditions. This review examines the clinical significance, histopathological correlation, and implications of HCF in various diseases, including diabetic retinopathy, age-related macular degeneration, Stargardt disease, choroideremia, Vogt-Koyanagi-Harada disease (VKH), idiopathic posterior uveitis, retinitis pigmentosa, and central serous chorioretinopathy (CSR), as well as non-pathological states. Although further studies are required to validate the findings in each pathology described herein, HCF may be used as a background prognostic marker of disease progression and therapeutic response, albeit with caution.},
}
@article {pmid41267136,
year = {2025},
author = {Choy, S and Chun, JM and Seok, JW and Park, SR and Kim, JD},
title = {Effectiveness of photobiomodulation therapy for ophthalmic diseases: protocol for a systematic review and meta-analysis of disease-specific and shared physiological outcomes.},
journal = {Systematic reviews},
volume = {14},
number = {1},
pages = {231},
pmid = {41267136},
issn = {2046-4053},
support = {KSN2511012//Korea Institute of Oriental Medicine/ ; },
mesh = {Humans ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; *Low-Level Light Therapy/methods ; *Eye Diseases/therapy/radiotherapy ; Research Design ; Treatment Outcome ; },
abstract = {BACKGROUND: Photobiomodulation therapy (PBMT)-a noninvasive therapeutic strategy-employs low-level red or near-infrared light to regulate cellular bioenergetics, reduce oxidative stress, and modulate inflammation. It has demonstrated therapeutic potential for several ophthalmic diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa, and dry eye disease. However, the clinical evidence remains fragmented due to heterogeneity in study designs, treatment parameters, and outcome measures. Moreover, existing reviews are largely confined to single diseases. Robust, prespecified assessments that standardize disease-specific endpoints and only explore shared physiological measures across conditions remain scarce.<br><br>METHODS: The protocol is registered in the PROSPERO database. This review will follow the PRISMA guidelines; randomized controlled trials and comparative nonrandomized clinical studies involving PBMT interventions for any clinically diagnosed ophthalmic disease will be included. Eligible comparators will include sham treatment, no treatment, or standard care, and outcomes will be primarily analyzed at the disease-specific level, with endpoints including best-corrected visual acuity, drusen volume, intraocular pressure, and diabetic retinopathy severity. Selected shared physiological or functional outcomes (e.g., electroretinogram amplitude, tear cytokine concentrations, and optical coherence tomography measurements of retinal structure) will be examined in a secondary exploratory framework to provide hypothesis-generating insights across conditions. Databases-including PubMed, Embase, Cochrane Library, Web of Science, and Scopus-will be searched for articles published up to July 31, 2025. Two reviewers will independently select studies, extract data, and assess risk of bias. Random-effects models will be used for the meta-analysis, and heterogeneity will be explored through prespecified subgroup (disease type, wavelength, irradiance, fluence, session duration, treatment frequency) and exploratory meta-regression analyses.<br><br>DISCUSSION: This review will provide pooled effect estimates for PBMT based on clinical outcomes across ophthalmic diseases. These will be stratified by intervention parameters and outcome types (disease-specific and shared physiological/biomarker-based). Rather than aiming to determine optimal treatment strategies, the findings are intended to provide exploratory insights and generate hypotheses for future clinical research. The study will synthesize clinical evidence regarding the effect of PBMT on ophthalmic diseases, highlighting methodological considerations to guide the design of future trials and serve as an exploratory framework for understanding potential multidisease and multioutcome perspectives.<br><br>PROSPERO CRD420251033569.},
}
@article {pmid41265309,
year = {2025},
author = {Parra-Sánchez, &#xc1; and Román-Vallina, A and Fernández, E and Martínez-Navarrete, G},
title = {Computational modeling of anti-VEGFA drug interactions with VEGF-A: Insights into therapeutic strategies for neovascular AMD.},
journal = {Computational biology and chemistry},
volume = {120},
number = {Pt 1},
pages = {108788},
doi = {10.1016/j.compbiolchem.2025.108788},
pmid = {41265309},
issn = {1476-928X},
abstract = {Vascular endothelial growth factor A (VEGF-A) is the main driver of pathological angiogenesis and represents the primary therapeutic target in neovascular age-related macular degeneration (nAMD). Several anti-VEGF agents are currently available, but systematic comparisons of their molecular interactions with VEGF-A remain limited. In this study, we performed the first integrated in silico evaluation of six clinically relevant anti-VEGF drugs: abicipar, aflibercept, bevacizumab, brolucizumab, faricimab, and ranibizumab. Structural modeling, residue conservation analysis, molecular docking (HADDOCK), and binding affinity prediction (PRODIGY) were employed to assess drug-VEGF-A interactions in terms of stability, energetic contributions, and key conserved residues. Our results showed that bevacizumab exhibited the most stable interaction profile, dominated by van der Waals forces and supported by highly conserved residues. Aflibercept displayed strong electrostatic stabilization, while ranibizumab and brolucizumab achieved robust interactions through mixed forces. Faricimab presented weaker binding stability but its dual-target mechanism, involving VEGF-A and angiopoietin-2, may extend its therapeutic efficacy beyond VEGF-A inhibition. Abicipar demonstrated favorable stability despite structural differences from conventional antibodies. Notably, hydrophobic interactions were consistently identified as a central determinant of complex stability across all drugs, whereas an excess of charged residues correlated with reduced affinity. This systematic analysis highlights the coexistence of evolutionary conservation and rational molecular engineering as complementary strategies shaping anti-VEGF drug performance. Overall, our findings demonstrate that computational modeling offers a cost-effective and predictive tool to guide the optimization of current therapies and the rational design of next-generation anti-VEGF agents for nAMD and other retinal vascular disorders.},
}
@article {pmid41264299,
year = {2025},
author = {Yee, H and Wong, CMJ and Gupta, P and Thakur, S and Fenwick, E and Lamoureux, EL and Man, REK},
title = {Prevalence, Risk Determinants, and Burden of Undiagnosed Age-Related Eye Diseases Among Older Asian Adults.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41264299},
issn = {2168-6173},
abstract = {IMPORTANCE: While population-based surveys have identified a high prevalence of undiagnosed eye diseases among Asian adults, these studies were conducted more than a decade ago, and there is a paucity of contemporary data.<br><br>OBJECTIVES: To determine the contemporary prevalence of undiagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and glaucoma and their shared risk determinants and to evaluate these conditions' patient-centered and economic burden in a large multiethnic cohort of older Asian adults.<br><br>This cross-sectional cohort study was conducted among individuals from the Population Health and Eye Disease Profile in Elderly Singaporeans study (PIONEER-1, conducted from December 2017 to November 2022), a population-based cohort of community-dwelling individuals of Chinese, Malay, and Indian ethnicity aged 60 years or older living in Singapore. Data analysis was performed from April 2024 to December 2024.<br><br>EXPOSURES: The 4 eye diseases were diagnosed clinically by a study ophthalmologist; participants were considered undiagnosed if no prior physician diagnosis or related interventions were reported.<br><br>MAIN OUTCOMES AND MEASURES: One primary outcome, visual impairment (VI), was assessed clinically using the logMAR chart at 4 m by certified optometrists, while key patient-centered and economic outcomes were assessed using validated questionnaires.<br><br>RESULTS: This study was conducted among 1878 individuals from the PIONEER-1 study, among whom mean (SD) age was 72.7 (8.3) years and 1013 participants (53.9%) were female. A total of 742 participants (weighted prevalence: 35.8%) had at least 1 type of undiagnosed eye disease, with 650 participants (87.6%), 87 participants (11.7%), and 5 participants (0.7%) having 1, 2, and 3 conditions, respectively. Among individuals with AMD, DR, cataracts, or glaucoma, the weighted prevalences of undiagnosed disease were 89.8%, 89.8%, 40.8%, and 48.1%, respectively. Younger age (odds ratio [OR], 1.08 per year decrease; 95% CI, 1.06-1.10; P&#x2009;<&#x2009;.001), wearing multifocal glasses (OR, 1.75; 95% CI, 1.19-2.59; P&#x2009;=&#x2009;.005), and Malay (OR, 1.71; 95% CI, 1.21-2.43; P&#x2009;=&#x2009;.003) and Indian (OR, 1.43; 95% CI, 1.00-2.04; P&#x2009;=&#x2009;.05) ethnicities compared with Chinese individuals were associated with greater odds of having undiagnosed eye disease. Individuals with undiagnosed eye diseases reported -1.97% to -4.57% lower scores in health- and vision-related quality of life, as well as a greater likelihood of having VI (OR, 2.46; 95% CI, 1.68-3.61; P&#x2009;<&#x2009;.001). Additionally, undiagnosed individuals incurred 1.73-fold higher health care expenditures compared with those who were diagnosed (diagnosed: reference; undiagnosed: OR, 1.73; 95% CI, 1.06-2.84; P&#x2009;=&#x2009;.03).<br><br>CONCLUSIONS AND RELEVANCE: In this cross-sectional cohort study, the rates of undiagnosed age-related eye diseases were relatively high, and these conditions were associated with poorer patient-centered outcomes and greater health care expenditure. These results support the use of community eye screening services and health awareness campaigns targeted toward individuals at the lower end of the older than 60 years spectrum and those of Malay and Indian ethnicities to mitigate the detrimental effects of undiagnosed eye diseases in these individuals.},
}
@article {pmid41263219,
year = {2025},
author = {Dang, TM and Invernizzi, A and Nguyen, V and Hashimoto, Y and Romano, F and Cozzi, M and Arnold, J and Wong, J and Mehta, H and Fraser-Bell, S and Barry, R and Barthelmes, D and Gillies, M and Luckie, A},
title = {Twelve-Month Outcomes of Brolucizumab in Routine Clinical Practice: Fight Retinal Blindness! Registry.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.70033},
pmid = {41263219},
issn = {1442-9071},
support = {//Novartis/ ; },
abstract = {BACKGROUND: We analysed 12-month real-world outcomes of treatment of eyes with neovascular age-related macular degeneration switched to brolucizumab from a first-generation VEGF inhibitor to determine whether switching chronically active eyes that required frequent treatment improved control of the disease safely with fewer injections.<br><br>METHODS: Retrospective analysis of Australian and Italian data from the prospectively designed observational Fight Retinal Blindness! registry. We studied eyes that switched to brolucizumab and received at least two injections with 12&#x2009;months of follow-up.<br><br>RESULTS: Of the 81 eligible eyes, the proportion of inactive lesions increased from 5% at baseline to 37% 12&#x2009;months after switching to brolucizumab (p&#x2009;<&#x2009;0.001). Mean (95% CI) visual acuity (VA) was stable (0.6 [-1.5, 2.8] letters, p&#x2009;=&#x2009;0.55), while median treatment intervals increased from 44 to 63&#x2009;days (p&#x2009;<&#x2009;0.001). Nearly a third (30%) of eyes switched back to another VEGF inhibitor within 12&#x2009;months. Eyes that stayed on brolucizumab had a significantly longer mean treatment interval at 12&#x2009;months than eyes that switched off it (66.1 [Q1, Q3: 56, 91] vs. 49 [28, 63.2] days, p&#x2009;&#x2264;&#x2009;0.001) while VA change and inactivation rates were similar. Intraocular inflammation (IOI) was recorded in 7 (9%) eyes receiving at least one injection of brolucizumab.<br><br>CONCLUSIONS: Eyes that switched from a first generation VEGF inhibitor to brolucizumab in routine clinical practice achieved a clinically significant extension of their treatment interval, with more than a third becoming inactive but with a relatively high rate of IOI.},
}
@article {pmid41262993,
year = {2025},
author = {Geetha, J and Govindhan, S and Kalifa, MRHM and Gaur, A and Varatharajan, S},
title = {Association of Visual Impairment and Falls in Elderly Individuals-A Cross-Sectional Study.},
journal = {Current health sciences journal},
volume = {51},
number = {2},
pages = {185-190},
pmid = {41262993},
issn = {2067-0656},
abstract = {BACKGROUND: Falls are considered to be the most frequent and significant cause of unintentional harm and mortality among the elderly. Impaired vision is a significant risk factor for falls.<br><br>AIM: To analyse the relationship between visual impairment and falls in the elderly.<br><br>METHODOLOGY: This hospital-based cross-sectional study included 270 participants after obtaining informed consent. Details of demographic profile, lifestyle, gait and balance deficits, ophthalmic and systemic condition were collected. The identification of independent risk variables for falls in the elderly was performed by logistic regression analysis.<br><br>RESULTS: Among 270 participants, 115 participants had falls. The mean age of fallers was 72.97 years. Females had significant falls. 87.8% of participants had visual impairment. Visual risk factors like cataract (80.9%), uncorrected refractive error (59.1%), glaucoma (24.3%), age-related macular degeneration (20.2%), and corneal opacity (13%) were very strongly associated with fall (P<0.001). On multivariate logistic regression analysis visual risk variables like Cataract, uncorrected refractive error and glaucoma had a significant association with falls (P<0.05) with an adjusted odds ratio (aOR) of less than 1. Diabetic retinopathy had strong association of fall (P<0.001) with aOR of 41.8 (95% CI 4.27-409.2).<br><br>CONCLUSION: Falls and visual impairment are public health concerns that require attention. Since many causes of visual impairment in the elderly are reversible, lowering the risk of falls in this population may be a controllable goal.},
}
@article {pmid41262233,
year = {2025},
author = {Abbas, A and Singaravelu, J and Fein, JG},
title = {Real-World Clinical Usage and Safety Profile of Intravitreal Pegcetacoplan in Age-Related Macular Degeneration-Associated Geographic Atrophy.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251387554},
pmid = {41262233},
issn = {2474-1272},
abstract = {Purpose: To examine the clinical usage and safety profile in real-world patients with age-related macular degeneration (AMD) receiving intravitreal pegcetacoplan (Syfovre) for the treatment of geographic atrophy, and to explore the effect of intravitreal pegcetacoplan on neovascular AMD (nAMD) disease activity. Methods: Information on patient demographics, AMD classification, treatment history, visual acuity, and ocular adverse events were extracted from the electronic medical records. Results: A total of 1069 patients (1451 eyes) initiated intravitreal pegcetacoplan treatment between February 2023 and October 2023 and were followed up until March 2024. Patients received a mean (±SD) 3.3 ± 2.1 injections, and the mean (±SD) follow-up after pegcetacoplan administration was 7.5 ± 2.3 months. The majority of this cohort displayed stable visual acuity throughout treatment, with logMAR values in 821 patients remaining within 0.20 of the initial value. Ocular hypertension occurred in 36 patients (2.5% of eyes). Seventy-six patients (5.2% of eyes) with non-neovascular AMD at treatment initiation subsequently developed nAMD. Five patients (0.34% of eyes) had intraocular inflammation, including 3 with anterior uveitis, 1 with nonocclusive retinal vasculitis, and 1 with hemorrhagic occlusive retinal vasculitis with subsequent poor outcomes. A rate of retinal vasculitis of 0.03% per injection and a rate of overall intraocular inflammation of 0.1% per injection were observed. In total, 460 patients with nAMD received intravitreal pegcetacoplan. Stability of the anti-vascular endothelial growth factor (anti-VEGF) treatment interval was observed in 289 of 396 patients (73%). Preserved or improved visual acuity while undergoing anti-VEGF therapy was noted in 384 of 396 patients (97%). Conclusions: Real-world data on intravitreal pegcetacoplan treatment identifies clinician practice patterns and demonstrates an acceptable safety profile, with complications leading to long-term vision loss following pegcetacoplan administration being rare in this cohort.},
}
@article {pmid41258608,
year = {2025},
author = {Sun, Y and Zhang, WY and Song, CL and Pan, ZQ and Du, GJ and Song, ZQ and Ren, J and Bo, LY and An, JJ and Wang, M},
title = {Effects of Plastein Reaction Mediated Corn Glutelin Hydrolysate on the Structure and Its Anti-Inflammatory Activity of ARPE-19 Cells in Vitro.},
journal = {Journal of food science},
volume = {90},
number = {11},
pages = {e70650},
doi = {10.1111/1750-3841.70650},
pmid = {41258608},
issn = {1750-3841},
support = {TSBICIP-KJGG-022//Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project/ ; 22HHSWSS00001//"Major Project" of Haihe Laboratory of Synthetic Biology/ ; 130212124135//Heilongjiang Education Department of Basic Business Project of China/ ; 145309403//Heilongjiang Education Department of Basic Business Project of China/ ; },
mesh = {*Anti-Inflammatory Agents/pharmacology/chemistry ; Humans ; *Protein Hydrolysates/chemistry/pharmacology ; Cell Line ; *Glutens/chemistry/pharmacology ; Antioxidants/pharmacology/chemistry ; *Zea mays/chemistry ; Amino Acids/chemistry ; Tumor Necrosis Factor-alpha/metabolism ; Retinal Pigment Epithelium/drug effects/cytology ; Interleukin-6/metabolism/immunology ; Interleukin-1beta/metabolism ; },
abstract = {Corn glutelin hydrolysate (CGH) has demonstrated potential diverse biological activities; however, its application in the food industry is often limited by physicochemical properties (e.g., peptide instability, solubility, or essential amino acid deficiency). The Plastein reaction, a very safe chemical reaction, involving exogenous amino acids (AAs), shows promise in altering the functionality of CGH. In this study, CGH was modified via the Plastein reaction using histidine, cysteine, or tryptophan to generate CGH-His, CGH-Cys, and CGH-Trp. These modified products with superior antioxidant activity and functional characteristics were screened out, and their anti-inflammatory activity was evaluated via an LPS-induced retinal inflammation ARPE-19 cell model. The results indicated that the free amino group contents of all three AA-modified CGHs were significantly lower than those of their corresponding mixtures (P < 0.05). Among the modifiers, CGH-Trp exhibited a significantly enhanced DPPH radical scavenging rate (78.66%), hydroxyl radical scavenging rate (58.35%), ABTS radical scavenging rate (83.29%), and average particle size (381.67 nm) (P < 0.05), compared to unmodified CGH. Structural characterization analysis revealed that the incorporation of tryptophan led to peptide condensation and improved thermal stability. Furthermore, pre-treatment with 10 µg/mL of CGH-Trp significantly reduced the secretion of TNF-α, IL-6, and IL-1β by 33.46%, 32.17%, and 44.49%, respectively, in ARPE-19 cells, compared to the LPS-induced group. This study confirms that the Plastein reaction promotes peptide condensation in CGH in the presence of exogenous amino acids and improves the characteristic, antioxidant, and anti-inflammatory activities, highlighting its potential as a preventive strategy for age-related macular degeneration (AMD).},
}
@article {pmid41258038,
year = {2025},
author = {Barbosa, M and Bartolomeo, N and Schuetz, YP and Nascimbeni, AC and Castro, DG and Barry, MP and Ambresin, A},
title = {Intravitreal faricimab in patients with aflibercept-refractory neovascular age-related macular degeneration: short and long-term outcomes and assessment of volume dynamics using an artificial intelligence-based tool.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {126},
pmid = {41258038},
issn = {2056-9920},
abstract = {PURPOSE: This study assessed the short- and long-term outcomes of intravitreal (IVT) faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. The main aim was to investigate whether faricimab might enable longer treatment intervals versus aflibercept through improved fluid control, evaluated through use of an artificial intelligence-based quantification tool to evaluate retinal fluid dynamics.<br><br>METHODS: This observational cohort study involved patients with refractory nAMD who received at least three consecutive IVT aflibercept 2.0&#xa0;mg injections before switching to IVT faricimab (with a four-month loading phase followed by a treat-and-extend regimen) due to persistent or recurrent disease despite 4-8-week treatment intervals. Functional and anatomical outcome measures were recorded, and fluid volume dynamics were quantified, at baseline, monthly to Month 4, and at Months 6, 9, and 12.<br><br>RESULTS: Seventy-four eyes from 60 patients were included, with a mean&#x2009;&#xb1;&#x2009;standard deviation duration of prior aflibercept therapy of 24&#x2009;&#xb1;&#x2009;17 months. Fifty-two eyes completed 12-month follow-up. At Month 12, mean best-corrected visual acuity showed no significant change from baseline (+&#x2009;0.01 Early Treatment of Diabetic Retinopathy Study letters, p&#x2009;=&#x2009;0.64). Significant reductions in mean central retinal thickness (-&#x2009;80.8&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.0001) and maximal pigment epithelium detachment (PED) height (-&#x2009;28.2&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.011), were observed at Month 4 and maintained to Month 12. Mean fluid volumes (intraretinal fluid [IRF], subretinal fluid [SRF]), and PED decreased significantly at Month 4 (-&#x2009;26.3 nL, p&#x2009;=&#x2009;0.007; -41.5 nL, p&#x2009;=&#x2009;0.0001; and -&#x2009;175.4 nL, p&#x2009;=&#x2009;0.0001, respectively). At Month 12, reductions in IRF and PED volumes were sustained. The maximal fluid-free interval increased from 4.4 weeks, prior to switching to faricimab, to 6.5 weeks (p&#x2009;=&#x2009;0.001) after switching, while mean last treatment interval improved from 5.0&#x2009;&#xb1;&#x2009;1.4 weeks at baseline to 7.3&#x2009;&#xb1;&#x2009;2.6 weeks at month 12 (p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: Faricimab may offer a valuable alternative for patients with refractory nAMD. The use of four loading injections administered monthly, followed by a treat-and-extend regimen can result in maintenance of visual acuity and improve anatomical parameters and retinal fluid activity, allowing for longer treatment intervals.},
}
@article {pmid41254090,
year = {2025},
author = {Wolfram, L and Schwämmle, M and Gimpel, C and Merle, DA and Tang, J and Clark, SJ and Böhringer, D and Schlunck, G},
title = {Extracellular matrix stiffness modulates angiogenic properties of the retinal pigment epithelium.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {40349},
pmid = {41254090},
issn = {2045-2322},
mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; *Extracellular Matrix/metabolism ; Humans ; *Neovascularization, Physiologic ; Cell Line ; Vascular Endothelial Growth Factor A/metabolism ; Culture Media, Conditioned/pharmacology ; Thrombospondin 1/metabolism ; Bruch Membrane/metabolism ; Macular Degeneration/metabolism/pathology ; },
abstract = {Physiological and pathological processes, such as aging and basal deposit aggregation in degenerative retinal diseases like age-related macular degeneration (AMD), alter the mechanical properties of Bruch's membrane (BrM). These mechanical changes in the extracellular matrix (ECM) significantly affect retinal pigment epithelial (RPE) cells, influencing their morphology, transcriptome and angiogenic behavior. ARPE-19 cells were cultured on hydrogels of physiological stiffness (30 and 80 kPa) and on conventional tissue culture plastic (TCP) for comparison. Gene expression was analyzed by droplet digital PCR (ddPCR), while protein-level changes were examined using immunofluorescence (IF), Western blotting (WB) and enzyme-linked immunosorbent assays (ELISA). Stiffness-dependent modulation of endothelial cells by RPE-conditioned media was investigated using in vitro angiogenesis assays. RPE cells cultured on softer substrates exhibited enhanced angiogenic properties, including increased expression of CD44 and vascular endothelial growth factor (VEGF). In contrast, stiffer substrates promoted antiangiogenic responses, associated with altered distribution of thrombospondin 1 (THBS1). These findings underscore the importance of ECM mechanics in modulating angiogenic signaling and highlight their potential relevance in retinal pathologies such as AMD. Local disruptions in adhesion or mechanical cues, potentially caused by basal deposits, may contribute to proangiogenic behavior even in the context of globally increased tissue stiffness with age.},
}
@article {pmid41251528,
year = {2025},
author = {Singh, SR and Sadeghi, E and Schulman, A and Du, K and Gandhi, P and Narayan, SA and Arora, S and Ibrahim, MN and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Chhablani, J},
title = {Comparison of Three-Dimensional Choroidal Contour in Patients With Neovascular Age-Related Macular Degeneration and Their Fellow Eyes.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {11},
pages = {26},
pmid = {41251528},
issn = {2164-2591},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Cross-Sectional Studies ; *Choroid/diagnostic imaging/pathology ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnostic imaging ; *Imaging, Three-Dimensional/methods ; Aged, 80 and over ; *Choroidal Neovascularization ; Middle Aged ; Macular Degeneration ; },
abstract = {PURPOSE: To compare the three-dimensional choroidal contour map of patients with neovascular age-related macular degeneration (nAMD) and their fellow eyes.<br><br>METHODS: This cross-sectional study included 30 patients with nAMD in one eye and early/intermediate AMD in the fellow eye. Wide-field (12 &#xd7; 12 mm) swept source optical coherence tomography volumetric scans were obtained. Choroidal inner boundaries (CIBs) and choroidal outer boundaries (COBs) were delineated based on our previously reported deep learning model. Best-fit spherical radius (R, mm) was calculated for CIB and COB and compared in both groups using paired t tests. The regional variation of RCIB and RCOB in different sectors (superior, inferior, nasal, temporal, and central) was compared. P values of &#x2264;0.05 were considered statistically significant.<br><br>RESULTS: The mean RCIB was 32.8 &#xb1; 8.6 mm and 32.5 &#xb1; 9.4 mm in nAMD group and their fellow eyes, respectively (P = 0.80). Similarly, the mean RCOB was 31.3 &#xb1; 7.0 mm in the nAMD group with no statistically significant variation in their fellow eyes (early/intermediate AMD, 31.5 &#xb1; 9.0 mm; P = 0.88). Comparison of RCIB (nAMD, 15.0 &#xb1; 9.1 mm; fellow eye, 15.2 &#xb1; 10.4 mm; P = 0.91) and RCOB (nAMD, 13.6 &#xb1; 8.1 mm; fellow eye, 12.2 &#xb1; 9.0 mm; P = 0.48) in the central sector where AMD lesions were located was not significant. Intragroup sectoral comparisons of RCIB and RCOB in both groups were statistically significant (all P values < .01).<br><br>CONCLUSIONS: RCIB and RCOB exhibited significant regional variations across different sectors in both eyes, including nAMD and fellow eyes. However, the comparison of RCIB and RCOB between the two groups was not significantly different.<br><br>TRANSLATIONAL RELEVANCE: The study of choroidal contour may help to understand the pathological changes in age-related macular degeneration.},
}
@article {pmid41248379,
year = {2025},
author = {Shumye, AF and Desalegn, GK and Tegegn, MT and Worku, EM and Lorato, MM and Bogale, ZM and Tegegne, MM and Alimaw, YA and Mengistu, HG and Bekele, MM and Bayabil, AZ and Birhan, GS and Eticha, BL},
title = {Burden and predictors of age-related macular degeneration among old age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia: a multicentre cross-sectional prospective study.},
journal = {BMJ open},
volume = {15},
number = {11},
pages = {e105305},
pmid = {41248379},
issn = {2044-6055},
mesh = {Humans ; Ethiopia/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Macular Degeneration/epidemiology/etiology ; Aged ; Middle Aged ; Prospective Studies ; Risk Factors ; Hospitals, Special/statistics &amp; numerical data ; *Diabetes Mellitus/epidemiology ; Prevalence ; Aged, 80 and over ; Adult ; Age Factors ; },
abstract = {OBJECTIVE: This study aims to assess the burden and predictors of age-related macular degeneration (AMD) among older age patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia.<br><br>DESIGN: A multicentre cross-sectional study was conducted among older patients with diabetes using a systematic random sampling technique.<br><br>SETTING: The study was conducted at five comprehensive specialised hospitals in Northwest Ethiopia from 8 May to 8 June 2023.<br><br>PARTICIPANTS: The study included 832 diabetic individuals aged 40 years and above.<br><br>MAIN OUTCOME MEASURES: Data were collected using a pretested structured questionnaire and physical examinations.<br><br>RESULT: In this study, a total of 832 participants were involved, with a response rate of 96.85%. The burden of AMD was 15.4% (95% CI 13.0% to 18.0%). Male sex (adjusted OR (AOR) 2.04, 95%&#x2009;CI 1.17 to 3.56), older age (AOR 6.91, 95%&#x2009;CI 3.17 to 15.08), diabetes duration of 10 and more years (AOR 3.00, 95%&#x2009;CI 1.91 to 4.69), higher body mass index (AOR 2.56, 95%&#x2009;CI 1.15 to 5.71), presence of hypertension (AOR 2.45, 95%&#x2009;CI 1.56 to 3.85) and family history of diabetes mellitus (DM) (AOR 2.29, 95%&#x2009;CI 1.40 to 3.76) were positively associated with AMD.<br><br>CONCLUSIONS: This study found that the prevalence of AMD among patients with diabetes was 15.4%. Older age, male sex, longer DM duration, higher body mass index, presence of hypertension and family history of DM were significantly associated with AMD. Targeted screening of at-risk individuals for AMD, public health awareness campaigns focusing on these factors and further research to understand the burden and underlying mechanisms of these associations with AMD are recommended.},
}
@article {pmid41248269,
year = {2025},
author = {Starr, MR and Bakri, SJ},
title = {Response to Letter to the Editor regarding: "10-year Follow-Up of Patients with Exudative Age-Related Macular Degeneration Treated with Intravitreal Anti-VEGF Injections".},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004729},
pmid = {41248269},
issn = {1539-2864},
}
@article {pmid41248230,
year = {2025},
author = {Fragiotta, S and Sacconi, R and Beretta, F and Querques, G},
title = {Basal Laminar Deposits and Pseudodrusen: Rethinking Their Role in AMD Progression.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004683},
pmid = {41248230},
issn = {1539-2864},
abstract = {PURPOSE: To explore the association between basal laminar deposits (BLamD) and pseudodrusen and its clinico-prognostic significance in the context of age-related macular degeneration (AMD).<br><br>METHODS: A comprehensive narrative review of the literature was conducted, focusing on histopathological, clinical, and imaging studies that examine BLamD and subretinal drusenoid deposits (SDD) in AMD. Histopathological and clinical studies were analyzed to understand the composition, distribution, and clinical significance of these deposits.<br><br>RESULTS: Imaging and histological studies suggest that BLamD may serve as an indicator of AMD severity. BLamD is consistently observed in eyes with pseudodrusen and is characterized by a thin double layer sign in vivo with a hyporeflective interior. On fundus autofluorescence, BLamD retain an intrinsic autofluorescence, leading to a dark grey appearance of the nascent atrophic lesions. The association with SDD, also known as reticular pseudodrusen (RPD), can synergically affect the outer retina and retinal pigment epithelium, leading to a rapidly progressive atrophy.<br><br>CONCLUSION: BLamD is a key pathological feature in AMD, particularly in eyes with pseudodrusen. Their presence may contribute to disease progression, highlighting the need for further research into their prognostic significance and potential as therapeutic targets. A critical consideration is the need to improve multimodal imaging recognition, facilitating their identification in future clinical studies.},
}
@article {pmid41247476,
year = {2025},
author = {Rosso, WC and Chakravarthy, U and Girado, SEM and Rosenstiehl, S and Peto, T and Rodriguez, FJ},
title = {Characterization of subretinal hyperreflective material and short-term visual acuity in patients with neovascular age related macular degeneration after loading dose with antiangiogenics.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41247476},
issn = {1435-702X},
abstract = {PURPOSE: This study analyzes the morphological characteristics of subretinal hyperreflective material (SHRM) and its relationship with short-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial grown factor (anti-VEGF) at the Fundación Oftalmológica Nacional between 2011 and 2017.<br><br>METHODOLOGY: An analytical observational study was conducted on 65 treatment-na&#xef;ve nAMD patients who initiated treatment between January 2011 and December 2017. Spectral-Domain Optical Coherence Tomography (SD-OCT) was graded to determine quantitative and qualitative SHRM characteristics. SHRM features and best corrected visual acuity (BCVA) were correlated before and after treatment, and associations between SHRM characteristics and BCVA improvement after the loading phase were analyzed.<br><br>RESULTS: The median age was 75.5 years (range 68-84), and 56.9% were women. Aflibercept was the most widely used anti-VEGF (40%). Median BCVA improved from 0.8 logMAR (range 0.5-1.2) to 0.7 logMAR (range 0.4-1) after treatment. At baseline, a significant correlation was found between worse BCVA and SHRM horizontal extension (r=0.7, p=0.001), low reflectivity (p=0.017), and undefined margins (p=0.037). SHRM characteristics associated with BCVA improvement after treatment included low reflectivity (p=0.048), non-homogeneity (p=0.048), smaller width (p=0.043), and the presence of the external limiting membrane (ELM) (p=0.002) and ellipsoid zone (EZ) (p=0.017).<br><br>CONCLUSION: SHRM features such as low reflectivity, non-homogeneity, reduced width, and the presence of ELM/EZ were associated with improved short-term visual outcomes. These findings provide insight into favorable short-term SHRM characteristics, which may help establish early treatment criteria and support its role as a prognostic biomarker.<br><br>KEY MESSAGES: WHAT IS KNOWN : Neovascular age-related macular degeneration (nAMD) is a progressive disease that severely impacts vision if untreated. Subretinal hyperreflective material (SHRM) is a recognized biomarker on spectral-domain optical coherence tomography (SD-OCT) and has been studied as a predictor of long-term visual outcomes in patients treated with anti-VEGF therapy.<br><br>WHAT IS NEW: This study evaluates SHRM characteristics and their relationship with short-term visual outcomes after the loading dose of anti-VEGF treatment.SHRM features such as low reflectivity, undefined borders, smaller horizontal extent, and the presence of external limiting membrane (ELM) and ellipsoid zone (EZ) are associated with early visual improvement. SHRM features such as low reflectivity, undefined borders, smaller horizontal extent, and the presence of external limiting membrane (ELM) and ellipsoid zone (EZ) are associated with early visual improvement. These findings suggest that SHRM morphology could serve as an early prognostic biomarker, potentially guiding treatment decisions for better visual outcomes.},
}
@article {pmid41247474,
year = {2025},
author = {Vahldiek, A and Heine, L and Vahldiek, B and Schröter, J and Wolf, JN and Swora, M and Reissberg, L and Pauleikhoff, L and Kleesiek, J and Pauleikhoff, D},
title = {Automated measurement of macular neovascularization lesion size in nAMD using AI segmentation.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41247474},
issn = {1435-702X},
abstract = {PURPOSE: To compare artificial intelligence (AI)-based annotations of hyperreflective material (HRM) and manual demarcation of macular neovascularization (MNV) on optical coherence tomography (OCT) volume scans in neovascular age-related macular degeneration (nAMD), and to assess the suitability of AI-driven OCT segmentation for longitudinal lesion monitoring.<br><br>METHODS: In this retrospective study, 42 eyes from 36 patients (21 f, 15&#xa0;m; mean age baseline 76.6 y) with exudative nAMD were analyzed using longitudinal spectral-domain OCT data. Manual MNV demarcations on en-face OCT projections served as ground truth and were compared to AI-predicted HRM segmentations generated by a 3D nU-Net model on OCT scans. HRM and MNV lesion areas were quantified at multiple time points, and agreement between manual and AI-based measurements was evaluated using Pearson correlation, ordinary least squares regression and robust regression.<br><br>RESULTS: A highly similar mean lesion growth was observed when comparing HRM/MNV lesion sizes in longitudinal measurements. Point-by-point comparison revealed a strong overall correlation (r&#x2009;=&#x2009;0.78) between AI-predicted and manually annotated HRM areas with increasing significance with longer follow-up. However, two aspects were responsible for some AI measurements being larger than manual measurements: At baseline, AI measurements included hyperreflective subretinal fluid as HRM, which was resorbed after three anti-VEGF injections, and during longer-term follow-up, manually annotated MNV areas were occasionally smaller than those derived from AI-based HRM segmentation due to the manual underestimation of very thin HRM.<br><br>CONCLUSIONS: AI-based segmentation of HRM on OCT scans demonstrates strong overall agreement with manual MNV measurements, particularly on longitudinal assessments. Despite some AI-based overestimations occurring at baseline and some manual MNV underestimations during follow-up, measurements between both methods were highly comparable over time.},
}
@article {pmid41245253,
year = {2025},
author = {Cen, S and Xie, S and Ibrahim, KS and Baran, MR and Li, X and Reilly, J and Tan, Z and He, Z and Shu, X},
title = {Modified Zhujing pill regulates RPE cholesterol metabolism and gut microbiota in an age-related macular degeneration mouse model.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1691360},
pmid = {41245253},
issn = {2235-2988},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Macular Degeneration/drug therapy/metabolism ; Mice ; Disease Models, Animal ; *Drugs, Chinese Herbal/pharmacology/administration &amp; dosage ; *Cholesterol/metabolism ; *Retinal Pigment Epithelium/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Male ; Cytokines/metabolism ; Cecum/microbiology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common retinal disorder, causing blindness in aged individuals. One of the traditional Chinese medicines, modified Zhujing pill (MZP), has been widely used to treat various ocular disorders, including AMD; however, its protective mechanisms remain elusive. In this study, we explored the functional role of MZP in high-fat-diet-fed mice, a commonly used model for AMD.<br><br>METHODS: Compounds of MZP water extract were identified by high-performance liquid chromatography (HPLC)/mass spectrometry (MS)/MS. The mice were divided into three groups: group 1 mice fed with control diet (CD), group 2 mice fed with high-fat diet (HFD), and group 3 mice fed with HFD for 12 weeks; groups 1 and 2 were then treated with physiological saline, while group 3 was treated with MZP for 4 weeks. The cholesterol level and expression of cholesterol homeostasis-associated genes, antioxidant genes, and proinflammatory cytokines in mouse tissues were measured using biochemical approaches. Mouse cecum microbiota compositions and metabolic functions were analyzed using 16rRNA sequencing and bioinformatics approach.<br><br>RESULTS: HFD-fed mice had high levels of cholesterol in the retinal pigment epithelial (RPE) cells, liver, and serum, a decreased expression of cholesterol homeostasis-associated genes and antioxidant genes in the RPE and liver, and an increased expression of proinflammatory cytokines. MZP treatment counteracted HFD-induced pathologic effects. Additionally, HFD altered cecum bacterial compositions and diversities associated with individual metabolic pathways. These metabolic pathways are involved in the biosynthesis of bacterial metabolites, mitochondrial function, oxidative stress, and inflammation. MZP reversed most of the changes back to control characteristics.<br><br>CONCLUSION: We postulate that the beneficial effects of MZP against AMD are possibly related to lowering the cholesterol level, suppressing oxidative stress and inflammation, and modulating gut microbiota and associated functions.},
}
@article {pmid41244992,
year = {2026},
author = {Kleinman, DM and Wykoff, CC and Borkar, DS and Guymer, RH and Kocab, AJ and Puscas, L and Wietholter, SC and Kesteloot, LL and Zacks, DN},
title = {ONL1204 for the Treatment of Geographic Atrophy: Phase Ib Study Evaluating Safety, Tolerability, and Efficacy.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100954},
pmid = {41244992},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the safety and tolerability of ONL1204, a novel, small peptide inhibitor of the fragment apoptosis stimulator receptor, for the treatment of patients with geographic atrophy (GA).<br><br>DESIGN: A phase Ib multicenter study involving a dose-escalation/open-label (DE/OL) component and a randomized, double-masked, sham-controlled natural history/treatment (NHS/T) component.<br><br>PARTICIPANTS: Patients aged &#x2265;55 years with GA secondary to age-related macular degeneration.<br><br>METHODS: Dose-escalation/OL patients received a single intravitreal injection of either 50 &#x3bc;g, 100 &#x3bc;g, or 200 &#x3bc;g of ONL1204 and were followed for 24 weeks. Participants in the NHS/T component were randomized (1:1:1) to either 50 &#x3bc;g or 200 &#x3bc;g of ONL1204 or sham injection, after a 24-week NHS phase. Two injections were administered 12 weeks apart, and patients were observed for an additional 12 weeks.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was safety, assessed by monitoring adverse events (AEs), ophthalmic examination, electrophysiology, fundus photography, fundus autofluorescence, and OCT. Additional endpoints included measurement of GA lesion area and best-corrected visual acuity.<br><br>RESULTS: Six patients were enrolled in the DE/OL component and 22 patients in the NHS/T component. All patients in the DE/OL component completed the study with no major safety findings or dose-limiting toxicities. Seventeen patients were randomized in the NHS/T component, with 15 patients completing the study. All ophthalmic AEs were mild or moderate in severity. ONL1204 demonstrated a favorable effect on GA lesion growth, with numerically favorable slower lesion growth compared with the fellow eye in the DE/OL component at 6 months and a numerically slower growth rate (mean difference [standard error of the mean] of -0.524 mm[2] [0.39]; P = 0.202) in the 200 &#x3bc;g ONL1204 group compared with the sham group in the treatment phase of the NHS/T component. There were no changes in the treatment group with respect to visual acuity suggestive of any safety issues.<br><br>CONCLUSIONS: ONL1204 was safe and well tolerated at all evaluated doses, with the potential to reduce GA lesion growth and improve vision. These results support further evaluation of ONL1204 in patients with GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41244990,
year = {2026},
author = {Tan, JCK and Montesano, G and Behning, C and Dunbar, HMP and Finger, RP and Tufail, A and Terheyden, JH and Holz, FG and Luhmann, UFO and Crabb, DP and , },
title = {Using the Rate of Global and Pointwise Microperimetry Change to Predict Structural Conversion in Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100950},
pmid = {41244990},
issn = {2666-9145},
abstract = {PURPOSE: Studies evaluating functional change in age-related macular degeneration (AMD) using microperimetry often measure the difference in global mean sensitivity at interval time points versus baseline. We evaluate the rate of global and pointwise microperimetry change in intermediate AMD (iAMD) in the multicenter MACUSTAR (Registration NCT03349801) study and assess their prognostic value in structural conversion to late-stage AMD.<br><br>DESIGN: Prospective study.<br><br>SUBJECTS: Four hundred forty-seven subjects with iAMD (Beckman classification) from 20 European sites.<br><br>METHODS: Subjects that underwent mesopic microperimetry on &#x2265;3 follow-up visits were included. Two methods of assessing functional progression were evaluated: (1) global mean sensitivity regression and (2) pointwise sensitivity regression at fastest progressing N number of locations (N from 1 to 10). Rates of microperimetry progression were then evaluated in an initial series of visits prior to structural conversion to late-stage AMD.<br><br>MAIN OUTCOME MEASURES: Area under the receiving operating characteristic (AUC) curves and Cox proportional hazard models were used to assess risk of structural conversion based on rate of functional progression.<br><br>RESULTS: The mean age of subjects was 72 (standard deviation 7) years. The median number of visits and duration of follow-up was 6 visits and 3 years, respectively. Structural conversion to late-stage AMD was observed in 80 (17.9%) eyes. In the visits prior to conversion, there was a greater rate of global mean sensitivity loss in eyes that eventually developed late-stage AMD compared with those that did not (-1.05 vs. -0.30 decibels/year, P < 0.001). The AUC for classifying structural conversion versus no conversion was 0.72 for global sensitivity progression and 0.75-0.76 for between 1 and 10 fastest progressing N pointwise locations. The rate of global (hazard ratio 1.7, confidence interval [CI] 1.4-2.0) and pointwise (hazard ratio 1.2, CI 1.2-1.3) microperimetry progression in the initial series of visits was significantly associated with structural conversion (P < 0.0001).<br><br>CONCLUSIONS: In the analysis of longitudinal microperimetry data from the MACUSTAR study, the rate of global and pointwise sensitivity change was significantly greater and strongly prognostic of eyes that developed structural conversion. Our findings support use of these trend-based pointwise analysis methods in assessing functional progression in iAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41244346,
year = {2025},
author = {Wang, Y and Jiang, D and Wang, Q and Cao, Y and Guo, H and Lu, Y and Tian, F},
title = {Three-dimensional tissue engineering and organoid technologies for retinal regeneration and therapy.},
journal = {Bioengineering &amp; translational medicine},
volume = {10},
number = {6},
pages = {e70051},
pmid = {41244346},
issn = {2380-6761},
abstract = {The human eye, a masterpiece of evolution, orchestrates the intricate process of vision. The retina is a tissue with a layered structure that plays a critical role in converting light signals into neural impulses interpretable by the brain. Various eye conditions such as glaucoma, retinitis pigmentosa, age-related macular degeneration, and other retinopathies are characterized by damage or degeneration in the retina. Recent strides in organoid cultivation and advanced three-dimensional (3D) bioengineering technologies offer promising avenues for potential therapeutic interventions. Compared to traditional two-dimensional cell culture models, which are non-natural and limited in accuracy, 3D models, including organoids, electrospinning constructs, microfabrication-based scaffolds, and hydrogel systems, are more delicate, especially in recapitulating tissue architecture, offering spatial patterning, and enabling vascularization. Retinal organoids are 3D multicellular structures derived from stem cells that can mimic the retina's layered architecture and functionality. However, their inherent complexity, including the presence of multiple differentiated cell types, may not be necessary for all disease modeling applications. In contrast, engineered 3D technologies can be tailored to specific retinal diseases by incorporating only the most relevant cell types, matrix stiffness, and spatial arrangements, offering greater experimental control and reproducibility in targeted therapeutic testing. In the following paper, we will discuss organoid generation in detail. Besides retinal organoids, bioprinting is another promising avenue for regenerative medicines. We further review a suite of 3D fabrication strategies, including inkjet and laser-assisted bioprinting, electrospun scaffolds, and hydrogel systems, and evaluate their current and potential applications in modeling retinal diseases and developing translational therapies. We will also delve into the contemporary advancements in retinal therapies, particularly emphasizing the roles and prospects of organoid and engineered 3D technologies.},
}
@article {pmid41244030,
year = {2025},
author = {Momenaei, B and Wakabayashi, T and Adams, OE and Wang, K and Regillo, CD and Spirn, M and Ho, AC and Hsu, J and Kaiser, R and Yonekawa, Y and Orlin, A and Garg, SJ},
title = {Short-Term Changes in Intraocular Pressure Following Intravitreal Injection of Pegcetacoplan.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251390791},
pmid = {41244030},
issn = {2474-1272},
abstract = {Purpose. To determine short-term changes in intraocular pressure (IOP) after intravitreal injection of 0.1 mL pegcetacoplan (Syfovre; Apellis Pharmaceuticals) for the treatment of geographic atrophy (GA). Methods. This prospective, interventional study evaluated a case series of patients with GA without corneal pathology or a history of vitreoretinal surgery who received pegcetacoplan injections. IOP was measured with a handheld applanation tonometer immediately prior to injection, immediately after injection, and at 5, 10, 20, and 30 minutes postinjection. Results. Fifty-one patients (total 73 eyes) were enrolled. The mean (±SD) preinjection IOP was 15.3 ± 3.3 mm Hg, which significantly increased to 40.2 ± 13.7 mm Hg (P < .001) immediately after injection. Subsequent IOP measurements showed a gradual decrease to 31.3 ± 11.6 mm Hg at 5 minutes (P < .001), 23.2 ± 9.7 mm Hg at 10 minutes (P < .001), 19.6 ± 8.6 mm Hg at 20 minutes (P < .001), and 16.4 ± 4.9 mm Hg at 30 minutes (P = .05) postinjection. No further treatment was required, except that the left eye of 1 patient with a history of primary open-angle glaucoma and persistent IOP elevation underwent anterior chamber tap 20 minutes after injection. Multivariate linear regression analysis revealed that a higher IOP at 30 minutes postinjection was significantly associated with the preinjection IOP (P = .004) and with a history of glaucoma (P = .019). Conclusions. Following pegcetacoplan injections, immediate IOP elevation was observed, which gradually declined within the first 30 minutes. Eyes with higher baseline IOP or a history of glaucoma exhibited higher postinjection IOP.},
}
@article {pmid41243864,
year = {2025},
author = {Cui, Y and Li, H and Fan, W and Wu, H and Wang, J and Qu, C and Pu, N and Tao, Y},
title = {Dialogue Between the Clock Gene Bmal1 and Retinopathy: What Is the Exact Relationship?.},
journal = {CNS neuroscience &amp; therapeutics},
volume = {31},
number = {11},
pages = {e70490},
pmid = {41243864},
issn = {1755-5949},
support = {221100310200//the Science and Technology Major Project of Henan Province/ ; 224200510013//the Zhongyuan Science and Technology Leading Talent Project/ ; },
mesh = {Humans ; *ARNTL Transcription Factors/genetics/metabolism ; Animals ; Circadian Rhythm/physiology/genetics ; *Retinal Diseases/genetics/metabolism ; Circadian Clocks/genetics/physiology ; Retina/metabolism ; CLOCK Proteins/genetics ; Diabetic Retinopathy/genetics ; },
abstract = {BACKGROUND: Circadian clock coordinates the physiologic and behavioral activities with a 24-hour solar rhythm to maintain the temporal homeostasis of the body. In the mammalian retina, the circadian system regulates the physiological function of this organ. The realm of ocular circadian rhythm has earned kinds of research interest as the circadian rhythms dysfunction will disrupt the retinal homeostasis. Bmal1 functions as a major transcriptional regulator of the circadian clock.<br><br>RESULTS: In the retina, Bmal1 mediates the processing of light information, sustains photoreceptor viability and governs neurotransmitter release. Moreover, Bmal1 gene is believed to be a pathologic cofactor of the diabetic retinopathy (DR), age-related macular degeneration (AMD), premature aging and refractive myopia. To date, the precise mechanisms underlying the pathological effects mediated by Bmal1 remain incompletely elucidated.<br><br>CONCLUSIONS: This review presents recent findings and evidence regarding the contributory role of Bmal1 in retinal degeneration and its deficits, while exploring its therapeutic potential. And th review provides a comprehensive analysis of the underlying mechanisms of the clock gene Bmal1 in other diseases, with the aim of offering insights into innovative therapeutic strategies for retinopathy.},
}
@article {pmid41242720,
year = {2025},
author = {Zheng, X and Mi, Y and Cao, Y and Tong, L and Wan, M},
title = {Plasma caffeine level as a protective factor against age-related eye diseases: a two-sample Mendelian randomisation study.},
journal = {The British journal of nutrition},
volume = {},
number = {},
pages = {1-7},
doi = {10.1017/S0007114525105291},
pmid = {41242720},
issn = {1475-2662},
abstract = {Traditional studies examining caffeine intake and age-related eye diseases (ARED) have shown inconsistent results, potentially related to variations in caffeine assessment methods. This two-sample Mendelian randomisation study investigated associations between plasma caffeine and four ARED: senile cataract, diabetic retinopathy (DR) and glaucoma and age-related macular degeneration (AMD). Summary data on genetically predicted plasma caffeine came from a genome-wide association study of 9876 European-ancestry participants across six population-based studies. ARED data were extracted from FinnGen Consortium clinical records. We further examined causal effects on glaucoma subtypes: primary open-angle glaucoma (POAG) and primary angle closure glaucoma (PACG) and assessed intraocular pressure (IOP) as a potential mediator. Higher genetically predicted plasma caffeine levels were associated with reduced risk of senile cataract (OR 0·84, 95 % CI 0·78, 0·90, P < 0·001), DR (OR 0·81, 95 % CI 0·74, 0·88, P < 0·001), glaucoma (OR 0·83, 95 % CI 0·73, 0·95, P = 0·008) and PACG (OR 0·74, 95 % CI 0·54, 0·99, P = 0·046). No associations were observed with AMD or POAG. Mediation analysis suggested that 41 % (95 % CI −0·14, −0·01) of caffeine’s effect on glaucoma was mediated by IOP. Our findings indicate that elevated plasma caffeine may protect against senile cataract, DR and glaucoma, but not AMD. Effects differed by glaucoma subtype, with IOP partially explaining the overall association. This study provides genetic evidence supporting caffeine’s role in mitigating ARED risk, highlighting its potential therapeutic implications.},
}
@article {pmid41237938,
year = {2025},
author = {Wang, Y and Xia, Z and Jia, L and Zhang, K and Wei, P and Han, G},
title = {Metabolomic biomarkers across plasma, serum, and ocular fluids in age-related macular degeneration: narrative review and evidence synthesis.},
journal = {Experimental eye research},
volume = {262},
number = {},
pages = {110749},
doi = {10.1016/j.exer.2025.110749},
pmid = {41237938},
issn = {1096-0007},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss globally. It is a degenerative disorder characterized by progressive macular damage and systemic metabolic dysregulation. Metabolomics elucidates relationships between metabolic alterations and disease phenotypes, providing scientific foundation for biomarker-driven predictive diagnostics. Current AMD staging predominantly relies on a linear classification based on clinical symptoms and imaging phenotypes. But metabolic alterations often precede morphological changes, providing a crucial window for early screening and intervention. Recent multi-biofluid metabolomic studies have identified key metabolic biomarkers, including glycerophospholipid pathway metabolites, acylcarnitines, branched-chain amino acids, and adenosine. They are predictive of transition from non-advanced to advanced stages. This review summarizes stage-specific metabolic biomarkers across AMD progression, such as 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (18:0-20:4 PC), sphingosylphosphorylcholine (LysoSM[d18:1]), lysophosphatidylcholine (LysoPC[18:4]), short-chain acylcarnitines (e.g., acetylcarnitine [C2]), long-chain acylcarnitines (e.g., linoleoylcarnitine [C18:2]), and valerylcarnitine (C5). These biomarkers may allow for timely intervention before irreversible visual impairment and underscore the importance of differential metabolic signatures between stable and progressive stages for early disease management. By unveiling the dynamic changes of these critical metabolites, and providing evidence for their prognostic value in stage transition, this review proposes an evidence-based foundation for early risk stratification and precision intervention in AMD.},
}
@article {pmid41237838,
year = {2025},
author = {Wei, Y and Hu, X and Liu, Y and Zhang, J and Zhao, L and Yang, J and Xie, Z and Shi, D and Ma, L},
title = {ALKBH5-mediated m6A modification of ID2 mRNA promotes choroidal neovascularization and subretinal fibrosis.},
journal = {Cellular signalling},
volume = {138},
number = {},
pages = {112237},
doi = {10.1016/j.cellsig.2025.112237},
pmid = {41237838},
issn = {1873-3913},
abstract = {Choroidal neovascularization (CNV) and subretinal fibrosis are pivotal in the pathogenesis of wet age-related macular degeneration (wAMD) and contribute significantly to blindness. The role of N6-methyladenosine (m6A) modifications in the progression of wAMD remains unclear. This study identifies a significant upregulation of the RNA demethylase A-ketoglutarate dioxygenase ALKB homolog 5 (ALKBH5) in macular samples of wAMD donors. Mechanistically, ALKBH5 enhances retinal microvascular endothelial cell (RMEC) migration, angiogenesis, and endothelial-mesenchymal transition (EndMT) by upregulating DNA binding/differentiation protein 2 (ID2). Further analysis reveals that ALKBH5 interacts with the YTHDF2 binding domain of the m6A reader, which recognizes the m6A sequence on ID2 mRNA. This interaction stabilizes ID2 mRNA and modulates its m6A methylation, thereby influencing the epigenetic network in wAMD. In laser-induced CNV mouse models, ALKBH5 knockdown significantly inhibits CNV and subretinal fibrosis while protecting the retinal photoreceptor layer, thus preserving visual function. This study highlights the ALKBH5-YTHDF2-ID2 axis as a critical regulator in wAMD and suggests it as a novel therapeutic target for subretinal fibrosis in wAMD.},
}
@article {pmid41236117,
year = {2025},
author = {Singerman, L and Gugiu, C and Tschosik, E and Doll, H and Singerman, B and Gentile, B},
title = {DERIVATION OF A SHORT FORM OF THE NATIONAL EYE INSTITUTE VISUAL FUNCTION QUESTIONNAIRE-25 IN SUBJECTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {2319-2328},
pmid = {41236117},
issn = {1539-2864},
mesh = {Humans ; *Visual Acuity/physiology ; Psychometrics ; Female ; Male ; Surveys and Questionnaires ; Aged ; *Wet Macular Degeneration/physiopathology/drug therapy ; *National Eye Institute (U.S.) ; Angiogenesis Inhibitors/therapeutic use ; Reproducibility of Results ; United States ; Ranibizumab/therapeutic use ; *Sickness Impact Profile ; Aged, 80 and over ; *Quality of Life ; Middle Aged ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: Develop a short form of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) using Rasch methodology in patients with neovascular age-related macular degeneration.<br><br>METHODS: Data on 32 items of the NEI VFQ-25 were analyzed from 1,294 patients in 3 studies of ranibizumab in neovascular age-related macular degeneration. Items were first grouped by visual function type; iterative multiple-group rating scale Rasch analyses were used to derive the Visual Function Questionnaire-Short Form (VFQ-SF). Item and scale-level VFQ-SF psychometric properties were assessed with estimation of meaningful within-patient change.<br><br>RESULTS: Fourteen of 32 items were eliminated initially; the final optimal subset included 7 items measuring 5 domains. The seven-item VFQ-SF had strong internal consistency (average item-total correlation 0.67, Cronbach alpha 0.88), test-retest reliability (intraclass correlation coefficient 0.79-0.91), and high NEI VFQ-25 composite score correlation (r = 0.93). Convergent (mean r = 0.76) and divergent (mean r = 0.24) validity were demonstrated. Known-groups validity was shown by mean VFQ-SF scores monotonically increasing with best-corrected visual acuity severity categories with large between group effect sizes (>2.8). Responsiveness was confirmed with VFQ-SF change linearly related to best-corrected visual acuity change. A meaningful within-patient change estimate of seven points was derived.<br><br>CONCLUSION: The seven-item VFQ-SF measures composite vision-related functioning, met all psychometric benchmarks, and is fit-for-purpose in neovascular age-related macular degeneration patients.},
}
@article {pmid41235805,
year = {2025},
author = {Hashimoto, Y and Reddie, I and Louw, Z and Gillies, M},
title = {Macular Atrophy in the Better-Seeing Eye of Australian Patients Treated for Neovascular Age-Related Macular Degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.70032},
pmid = {41235805},
issn = {1442-9071},
support = {//Roche/ ; //Bayer/ ; 1195021//National Health and Medical Research Council/ ; //Astellas/ ; //Apellis/ ; },
}
@article {pmid41235547,
year = {2025},
author = {},
title = {Correction to "Peptide-Bound Aflibercept Eye Drops for Treatment of Neovascular Age-Related Macular Degeneration in Nonhuman Primates".},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e19902},
doi = {10.1002/advs.202519902},
pmid = {41235547},
issn = {2198-3844},
}
@article {pmid41232694,
year = {2025},
author = {Rashid, M and Azeem, S and Shahid, IF and Ali, MKB and Shahid, F and Fatima, A and Rashid, A and Azeem, E},
title = {Efficacy and safety of aflibercept biosimilars compared to reference aflibercept for retinal diseases: A systematic review and meta-analysis.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.11.007},
pmid = {41232694},
issn = {1879-3304},
abstract = {Aflibercept biosimilars offer cost-effective alternatives to reference aflibercept for retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). By inhibiting vascular endothelial growth factor-mediated vascular damage, they aim to improve visual outcomes with comparable safety and efficacy, increasing treatment access while reducing cost burden. We evaluate their performance against the reference drug. A comprehensive search was done across Cochrane, Embase, PubMed, Scopus and ClinicalTrials.gov. Randomized controlled trials were included, and quality was assessed via RoB 2.0 tool. A random-effects model estimated standardized mean differences (SMD) and risk ratios. 11 studies (4064 participants) were analyzed, 8 focused on nAMD and 2 on DME. No significant differences in best-corrected visual acuity changes were observed between biosimilars and reference aflibercept in studies on nAMD (SMD = -0.04, 95 % confidence inerval [CI]: -0.15-0.06) or DME (SMD = 0.11, 95 % CI: -0.12-0.33). Central subfield thickness change at week 4 and the endpoint also showed no significant differences. Similarly, no significant differences were seen in choroidal neovacularization size, vision maintenance, anti-drug antibody development, treatment-emergent adverse events, or ocular adverse effects. Biosimilar aflibercept show similar efficacy and safety to the original for nAMD and DME, with no significant differences in key outcomes. They offer a cost-effective alternative that offers similar clinical benefits while improving treatment accessibility.},
}
@article {pmid41232598,
year = {2025},
author = {Yang, Z and Zhang, W and Gu, X and Zhao, X and Koh, A and Loewenstein, A and Li, B and Wang, C and Cheung, G and Zhang, J and Yang, J and Jin, K and Meng, L and Chen, L and He, M and Yuan, M and Luo, M and Li, N and Ruamviboonsuk, P and Yu, Q and Zhao, Q and Cheng, S and Sadda, SR and Peng, W and Zhang, X and Zhang, X and Liu, X and Wang, Y and Xu, Z and Xie, Z and Xu, Z and Ma, Z and Zhao, C and Chen, Y},
title = {Polypoidal Choroidal Vasculopathy: In-Depth Insights and Promising Future Directions.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101414},
doi = {10.1016/j.preteyeres.2025.101414},
pmid = {41232598},
issn = {1873-1635},
abstract = {Polypoidal choroidal vasculopathy (PCV) is an ocular condition predominantly affecting elderly individuals of Asian descent, characterized by the presence of polypoidal lesions and branching neovascular networks in the sub-retinal pigment epithelium (RPE) space. It has garnered increased attention for its potential differences from neovascular age-related macular degeneration. Genetic studies have identified specific genetic markers associated with PCV. Advances in imaging techniques, particularly optical coherence tomography (OCT) and OCT angiography, have significantly enhanced the diagnosis of PCV and our insight into its unique pathogenesis. Treatment strategies for PCV have evolved, with anti-vascular endothelial growth factor (VEGF) monotherapy becoming the primary treatment, and combination therapies including photodynamic therapy showing promising results. Consideration of targets beyond VEGF and the incorporation of artificial intelligence (AI) based analysis strategies may open the door to more personalized, precise, and effective treatments for patients. This review comprehensively discusses the current knowledge and recent advancements in PCV, including its epidemiology, genetics, biomarkers, pathogenesis, diagnosis, and management. It also highlights the need to explore mechanism underlying the higher prevalence of PCV in pigmented races, clarify the roles of pachychoroid and pachydrusen in PCV pathogenesis, and develop animal models that can better recapitulate the disease's pathological features.},
}
@article {pmid41231253,
year = {2025},
author = {Yu, Y and Sun, Y and Zhao, T},
title = {The roles of glycerophospholipids in the aging retina and age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41231253},
issn = {1435-702X},
support = {No. 2023SK2032//Key Research and Development Program of Hunan Province of China/ ; No. kq2502054//the Changsha Municipal Natural Science Foundation/ ; No. 2025JGB161//Project Program of central south university graduate education teaching reform/ ; },
abstract = {Glycerophospholipids (GPs) are integral constituents of cellular membranes, and play a crucial role in the regulation of lipid metabolism homeostasis and physiological conditions. However, pathological alterations associated with aging, such as variations in plasma GP concentrations, disruptions in intercellular GP transport, and local accumulation of excessive GPs, have been observed. These changes induce irreversible cellular degeneration, ultimately leading to tissue damage in organs such as the brain and retina. A growing body of evidences has demonstrated that GPs play significant roles in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Similarly, GPs have been implicated in the pathogenesis and progression of age-related macular degeneration (AMD), a degenerative condition affecting the choroid and retinal layers of the eye. Understanding the homeostasis of GP metabolism in the aging retina and in AMD is essential for elucidating the pathogenic processes involved in AMD. In this review, we present a comprehensive overview of the mechanisms of GPs in the aging retina and their correlation with degenerative processes associated with AMD. KEY MESSAGES: What is known Metabolic dysregulation of glycerophospholipids (GPs) plays vital roles in age-related macular degeneration (AMD) and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Patients with age-related neurological disorders exhibit a significantly higher risk of developing AMD compared to healthy individuals, potentially due to shared pathological mechanisms, including mitochondrial metabolic disturbance, chronic inflammation and autophagy dysfunction. What is new The interconnection between multiple GP species and their metabolites has been established to delineate complex pathogenic mechanisms underlying the aging retina and AMD, including cell senescence, autophagy and apoptosis, oxidative stress, inflammation, vascular abnormalities. GPs may serve as potential therapeutic targets to prevent or delay the progression of AMD.},
}
@article {pmid41230723,
year = {2025},
author = {Usmani, E and Bahrami, B and Ebneter, A and Chan, WO},
title = {Cessation of Anti-VEGF Treatment Therapy in Age-Related Macular Degeneration: A Narrative Review.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.70034},
pmid = {41230723},
issn = {1442-9071},
abstract = {Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionised the treatment of neovascular age-related macular degeneration (nAMD), significantly improving visual outcomes and enhancing the quality of life for affected patients. However, the decision to discontinue anti-VEGF therapy in nAMD management remains complex and lacks consensus, with various criteria being applied. This narrative review examines the available evidence on the cessation of anti-VEGF treatment in nAMD in detail.},
}
@article {pmid41230290,
year = {2025},
author = {Shloush, M and Eleff, A and Eleff, E},
title = {Ophthalmology Considerations in End-of-Life Care.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e94396},
pmid = {41230290},
issn = {2168-8184},
abstract = {Ophthalmologic interventions can significantly impact quality of life, even in the context of end-of-life care. This paper explores the ethical and clinical considerations for ophthalmologic treatments in hospice care, with a focus on cataract surgery, age-related macular degeneration (ARMD) therapy, retinal detachment (RD) repair, glaucoma, painful blind eye (PBE) management, benign and surface ocular tumors, and corneal or anterior segment diseases. A review of published literature and clinical precedent was conducted to assess the benefits, risks, and practical limitations of ophthalmologic procedures in hospice patients, with an emphasis on quality of life. Cataract surgery has been shown to be cost-effective in hospice settings, offering significant improvements in vision and overall quality of life. Treatment for ARMD, though requiring ongoing injections, can provide benefits within weeks and help sustain visual function. RD repair, while more complex, can substantially restore vision when appropriately managed. Palliative glaucoma interventions, including individualized target intraocular pressures and laser therapy, can minimize treatment burden while maintaining comfort. PBEs may be managed with retrobulbar chlorpromazine or alcohol injections, and enucleation or evisceration may be considered when pain persists. Benign or surface ocular tumors and corneal or anterior segment diseases can often be addressed with conservative, comfort-focused measures to reduce symptoms and preserve quality of life. Ophthalmologic procedures should be considered viable options in end-of-life care when clinically indicated, with careful ethical review. Restoration of vision contributes meaningfully to the quality of life and deserves thoughtful inclusion in care planning.},
}
@article {pmid41230077,
year = {2025},
author = {Sriram, R and Manayath, GJ},
title = {Subretinal injection of tissue plasminogen activator for submacular hemorrhage - When and how to do.},
journal = {Oman journal of ophthalmology},
volume = {18},
number = {3},
pages = {284-290},
pmid = {41230077},
issn = {0974-620X},
abstract = {Submacular hemorrhage (SMH) causes irreversible loss of vision as it causes permanent anatomical and functional damage to photoreceptors. The various causes include polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, retinal artery macroaneurysm, high myopia, and trauma. The current treatment modalities include antivascular endothelial growth factor (anti-VEGF) monotherapy, anti-VEGF ± gas pneumatic displacement ± intravitreal recombinant tissue plasminogen activator injection (rtPA), and triple therapy (intravitreal anti-VEGF + intravitreal rtPA + perfluoropropane gas injection). The surgical displacement of the SMH by vitrectomy with subretinal tissue plasminogen activator injection + intravitreal anti-VEGF + gas tamponade has been a valuable addition to our armamentarium. Evidence suggests that this novel technique provides better anatomical and functional outcomes in terms of visual acuity when the surgical displacement is performed within the prompt time frame in comparison to other available modalities of treatment. The current lacuna in the literature is the absence of level 1 evidence to support the surgical displacement as the first-line therapy. Hence, we review the current evidence and provide recommendations regarding this ever-promising therapy that can be vision-saving.},
}
@article {pmid41230053,
year = {2025},
author = {Ambiya, V and Kapoor, G and Sharma, VK},
title = {Large subfoveal pigment epithelial detachment causing macular hole formation: Surgical approach.},
journal = {Oman journal of ophthalmology},
volume = {18},
number = {3},
pages = {382-384},
pmid = {41230053},
issn = {0974-620X},
abstract = {Subfoveal pigment epithelial detachments (PEDs) have been reported to develop full-thickness macular hole (FTMH). The response to treatment has been varied in different reports, with most cases having persistent PED even after successful surgical closure of the macular hole. Here, we report an unusual case of nonneovascular age-related macular degeneration, having a large subfoveal serous PED, leading to the formation of a large FTMH, which showed complete flattening of the PED with a successful closure of the macular hole with the surgical approach.},
}
@article {pmid41229552,
year = {2025},
author = {Schuster, AK and Leisle, L and Picker, N and Vorwerk, H and Hahn, P and Wasem, J and Lewis, P},
title = {Economic and Medical Burden of Non-Exudative Age-Related Macular Degeneration in Germany: A Retrospective Observational Claims Data Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {4129-4144},
pmid = {41229552},
issn = {1177-5467},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in higher-income countries. This study aimed to explore the medical and economic burden of non-exudative AMD patients living in Germany.<br><br>METHODS: German claims data (AOK PLUS) were utilized in this retrospective analysis. Prevalent non-exudative AMD only patients were compared to (i) non-exudative AMD patients with a concomitant exudative AMD diagnosis and (ii) propensity score matched non-AMD controls in terms of patient characteristics and eye-related diagnostic/monitoring patterns during baseline (in 2020) as well as in terms of the healthcare resource use and associated costs during the follow-up (in 2021).<br><br>RESULTS: The sample comprised 25,439 patients diagnosed with non-exudative AMD only and 7,153 diagnosed with both types of AMD (mean age: 79/81 years | female: 64.3%/64.5%). The total health insurance costs for non-exudative AMD only patients were estimated to be 6,500 &#x20ac; per person-year (pPY), which was about 500 &#x20ac; pPY higher than in matched non-AMD controls. The total costs further increased by about 3,500 &#x20ac; pPY in the presence of concomitant exudative AMD. Also, the healthcare resources (especially related to ophthalmological care) were utilized more frequently by non-exudative AMD patients compared to non-AMD controls, and even more so by patients with concomitant exudative AMD.<br><br>CONCLUSION: Non-exudative AMD patients were associated with an increased medical and economic burden compared to non-AMD individuals living in Germany.},
}
@article {pmid41229226,
year = {2025},
author = {Rakic, N and Van Cauwenberge, F and Georges, A and Rakic, JM},
title = {[Early management of vitreous hemorrhage : clinical experience of the University Hospital of Liege].},
journal = {Revue medicale de Liege},
volume = {80},
number = {11},
pages = {703-707},
pmid = {41229226},
issn = {0370-629X},
mesh = {Humans ; *Vitreous Hemorrhage/surgery/therapy/diagnosis/etiology ; Retrospective Studies ; Male ; Female ; Aged ; Hospitals, University ; Middle Aged ; Vitrectomy ; Adult ; Aged, 80 and over ; Visual Acuity ; Young Adult ; },
abstract = {Hemorrhages occurring in the vitreous body have multiple etiologies. They cause an immediate and severe loss of visual acuity and sometimes require urgent surgical management by vitrectomy. We report in a retrospective series the clinical data of 76 patients treated at the University Hospital of Liège, highlighting the high incidence of retinal tears caused by posterior detachment of the vitreous body, the predominance of proliferative diabetic retinopathy in young patients, and that of age-related macular degeneration in older patients. Surgical intervention allows a very significant and fast improvement in visual acuity while avoiding the natural history of retinal tears which, in a hemorrhagic context, lead to retinal detachment with a very bad prognosis.},
}
@article {pmid41226778,
year = {2025},
author = {Dave, A and Tosevska, A and Morselli, M and Tom, E and Pellegrini, M and Skowronska-Krawczyk, D and Radu, RA},
title = {Dysregulated DNA Methylation in Abca4[-/-] Retinal Pigment Epithelium: Insights into Early Stage of Stargardt Disease.},
journal = {International journal of molecular sciences},
volume = {26},
number = {21},
pages = {},
pmid = {41226778},
issn = {1422-0067},
support = {1R01EY025002-05/NH/NIH HHS/United States ; 1R01EY000331-10/NH/NIH HHS/United States ; na//Research to Prevent Blindness, Inc./ ; },
mesh = {*DNA Methylation/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Stargardt Disease/genetics/pathology/metabolism ; Animals ; *ATP-Binding Cassette Transporters/genetics/metabolism ; Mice ; Disease Models, Animal ; Methyl-CpG-Binding Protein 2/metabolism/genetics ; Mice, Knockout ; *Macular Degeneration/genetics/congenital ; Epigenesis, Genetic ; Humans ; },
abstract = {Stargardt disease (STGD1), the most common inherited juvenile macular degeneration, is caused by biallelic mutations in the ABCA4 gene. Currently, there is no approved treatment. In this study, we investigated early-stage epigenomic changes in the retinal pigment epithelium (RPE) of Abca4[-/-] mice, a well-established model of STGD1. Reduced representation bisulfite sequencing (RRBS) revealed hypermethylation of gene regions associated with disease-related pathways, implicating methyl-CpG-binding protein 2 (MeCP2) and RE1-silencing transcription factor (REST) as potential regulators. Notably, DNA methylation of a subset of genes preceded their transcriptional change and disease phenotypes in Abca4[-/-] RPE. Together with the detected age-dependent increase in MeCP2 levels in Abca4[-/-] RPE, these findings suggest that early DNA methylation changes may contribute to RPE dysfunction and eventual cell loss in STGD1.},
}
@article {pmid41224521,
year = {2025},
author = {Yeo, D and Hwang, SH and Lee, S and Jeong, J and Kong, J and Lee, H and Smith, L and Cho, J and Yim, Y and Lee, J and Kang, J and Yang, JM and Yon, DK},
title = {Global, regional and national burden of major blindness-associated ophthalmologic conditions, 1990-2021, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327917},
pmid = {41224521},
issn = {1468-2079},
abstract = {BACKGROUND: The global burden of blindness and vision loss continues to increase, yet comprehensive analyses of underlying causes remain limited. This study estimated the global and regional burden of blindness-related diseases from 1990 to 2021 and projected trends to 2050 to inform public health strategies.<br><br>METHODS: We analysed data from the Global Burden of Disease Study (GBD) 2021 to estimate the prevalence and disability-adjusted life years (DALYs) rates of blindness and vision loss, focusing on six major causes, including glaucoma, cataract, age-related macular degeneration, refraction disorders, near vision loss and other vision loss. We quantified the contribution of risk factors, and future trends were projected to 2050 using GBD's forecast framework.<br><br>RESULTS: In 2021, the global age-standardised prevalence and DALY rates of blindness were 15&#x2009;784.3 (95% uncertainty interval (UI), 12&#x2009;761.4-19&#x2009;502.3) and 342.8 (224.2-503.6) per 100&#x2009;000. Although global age-standardised DALY rates remained statistically stable between 1990 and 2021, regional trends varied numerically. Southern sub-Saharan Africa recorded the highest age-standardised prevalence rate in 2021 at 16&#x2009;741.4 (13&#x2009;187.8-21&#x2009;129.5), whereas the highest DALY rate was observed in South Asia at 497.1 (345.3-691.6). While the overall burden of blindness did not differ significantly by sex, glaucoma showed a higher burden in males. From 1990 to 2021, cataract DALY rates attributable to household air pollution decreased by 38.4%, with projections showing stable age-standardised rates through 2050.<br><br>CONCLUSIONS: As populations age, the global burden of vision loss is projected to grow, with particularly high impact in lower-sociodemographic index regions such as Southern Sub-Saharan Africa and South Asia.},
}
@article {pmid41223128,
year = {2025},
author = {Spooner, KL and Fraser-Bell, S and Mehta, H and Hong, T and Broadhead, G and Wong, JG and Chang, AA},
title = {Lost to Follow-Up In Neovascular Age-Related Macular Degeneration: A Systematic Review of Global Trends, Risk Factors and Clinical Consequences.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1-30},
doi = {10.1159/000549177},
pmid = {41223128},
issn = {1423-0267},
abstract = {INTRODUCTION: Loss to follow-up (LTFU) among patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) remains a critical challenge for maintaining visual outcomes. This systematic review and meta-analysis evaluated the prevalence, risk factors, and impact on visual prognosis of LTFU across real-world studies.<br><br>METHODS: A comprehensive literature search of PubMed, Embase, Cochrane, Scopus and Google Scholar identified studies published between 2015 and 2025. Eligible studies included observational cohorts and registry-based analyses that reported the LTFU rates, risk factors, and visual outcomes following treatment discontinuation. Random-effects meta-analysis (DerSimonian-Laird) estimated pooled odds ratios (ORs) and 95 % confidence intervals (CIs); heterogeneity was assessed via I&#xb2; and Cochran's Q. Continuous predictors were analysed using regression-based odds ratios or standardised mean differences (SMDs), where appropriate.<br><br>RESULTS: We included 52 studies. Short-term loss to follow-up (LTFU) was defined as 6-12 months without treatment; long-term LTFU as &#x2265;12 months. LTFU rates ranged from <5% to >75% over up to 10 years. Older age was moderately associated with LTFU (SMD = 0.47, 95% CI 0.37-0.57; &#x2248;6-7 years older). Greater travel distance increased LTFU risk (OR = 1.35 per 10-km increase, 95% CI 1.14-1.60). Male sex (OR = 1.20, 95% CI 1.05-1.37) and caregiver/transport dependence (OR = 2.00, 95% CI 1.45-2.75) were also associated with a higher likelihood of LTFU. Treat-and-extend (T&amp;E) regimens showed lower LTFU than pro re nata (PRN). Patients who were LTFU had worse visual outcomes even after resuming care.<br><br>CONCLUSION: LTFU in nAMD treatment is common and driven by demographic (age, sex, and race), socioeconomic (income and insurance), and access (distance and caregiver need) factors. Continuous treatment, early response, and structured regimens (e.g., T&amp;E) mitigate dropout risk. Interventions to improve access and personalise support are essential to reduce LTFU and preserve visual outcomes.},
}
@article {pmid41223116,
year = {2025},
author = {Ottaiano-Poli, PA and Germano-Morrel, CS and Tomishige, KS and Macchione, RM and Kasahara, N},
title = {Comparison of balance-confidence between glaucoma and age-related macular degeneration patients who live in a developing country.},
journal = {Clinical rehabilitation},
volume = {},
number = {},
pages = {2692155251394989},
doi = {10.1177/02692155251394989},
pmid = {41223116},
issn = {1477-0873},
abstract = {ObjectiveTo compare balance-confidence among patients with primary open-angle glaucoma, age-related macular degeneration, and controls in Brazil.DesignCase-control study.SettingCharity hospital in São Paulo, Brazil.ParticipantsPatients with glaucoma, age-related macular degeneration, and controls without eye diseases.Main outcomes measuresActivities-specific Balance Confidence (ABC) Scale scores.ResultsThe sample consisted of 64 patients with glaucoma, 60 with age-related macular degeneration, and 60 controls. All groups were matched by age, gender, ethnic distribution, and comorbidities. The ABC Scale score was 63.1 (25.9) in the glaucoma group, 69.5 (16.4) in the age-related macular degeneration group, and 95.3 (9.1) for the controls (P < 0.001; Hedges' g -1.65 and -1.93, large effect size); glaucoma patients score did not differ from age-related macular degeneration patients (P = 0.132; Hedges' g 0.30, small effect size).ConclusionBoth glaucoma and age-related macular degeneration patients reported lower balance-confidence in performing daily activities without losing balance as compared to controls.},
}
@article {pmid41222660,
year = {2025},
author = {Fragiotta, S and Parravano, M and Costanzo, E and De Geronimo, D and Varano, M and Borrelli, E and Barresi, C and Sacconi, R and Querques, G},
title = {Early prediction of macular neovascularization phenotypes and prognostic evolution.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41222660},
issn = {1435-702X},
abstract = {PURPOSE: To investigate baseline predictors of macular neovascularization (MNV) phenotypes and prognostic outcomes, including changes in visual acuity (VA) and the development of macular atrophy (MA) and fibrosis.<br><br>METHODS: A retrospective, observational, cohort study was performed on a total of 102 eyes from 97 patients with intermediate age-related macular degeneration (AMD) converting to MNV subtypes. Baseline features, including age, drusen, reticular pseudodrusen (RPD), subfoveal choroidal thickness (SFCT), and central retinal thickness (CRT), were analyzed. Predictive models that considered the baseline characteristics predicting the different MNV subtypes and prognostic outcomes were developed using Cox regression and generalized linear models.<br><br>RESULTS: Of the included eyes, 68.6% developed type 1 MNV, 15.7% type 2 MNV, and 15.7% type 3 MNV. SFCT was a significant predictor of type 2 MNV, with thicker choroid predisposing to the lesion development (HR: 1.02, CI95%: 1, 1.03, p&#x2009;=&#x2009;0.001). Age was the primary predictor for type 3 MNV (HR: 1.1, CI 95%: 1, 1.2, p&#x2009;=&#x2009;0.02). Type 2 MNV exhibited the highest rate of fibrosis at follow-up (71.4%), compared to both type 1 (43.5%) and type 3 MNV (26.7%) (p&#x2009;=&#x2009;0.04). Age at baseline and best-corrected visual acuity (BCVA) were factors associated with final vision loss (p&#x2009;<&#x2009;0.001), while the presence of drusen alone appeared protective (p&#x2009;=&#x2009;0.03). SFCT at baseline also reduced the risk of outer retinal atrophy (p&#x2009;=&#x2009;0.01).<br><br>CONCLUSIONS: SFCT served as a key indicator for type 2 MNV while aging predominantly predicted type 3 MNV. The findings may improve the early identification and tailored management of MNV phenotypes, optimizing visual outcomes and mitigating complications such as fibrosis and atrophy.},
}
@article {pmid41222493,
year = {2025},
author = {Pan, SY and Chao, TF and Weng, CH and Lin, JF and Lin, CH and Lin, HJ and Wang, IJ and Chou, CC},
title = {Association between atrial fibrillation and age-related macular degeneration: A multinational cohort study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70028},
pmid = {41222493},
issn = {1755-3768},
support = {TCVGH-1136902B//Taichung Veterans General Hospital/ ; },
abstract = {PURPOSE: To assess whether atrial fibrillation (AF) is associated with an increased risk of age-related macular degeneration (AMD).<br><br>METHODS: This multinational retrospective cohort study included individuals aged 50&#x2009;years or older, with or without AF at baseline, from healthcare organisations across 21 countries during 2015-2020 in the TriNetX database. Participants were classified into those with and without AF, and followed for up to 5&#x2009;years to observe the occurrence of AMD, including both dry and wet forms, and other cerebrovascular outcomes. The AF and non-AF groups were 1:1 propensity score-matched to balance baseline characteristics and comorbidities. Outcomes were assessed using Cox regression models and Kaplan-Meier analysis.<br><br>RESULTS: A total of 113&#x2009;974 individuals were included in the final analysis. The mean follow-up (standard deviation [SD]) is 4.09 (1.30) years in the AF group and 4.53 (0.95) years in the non-AF group. During follow-up, 1169 individuals developed AMD, 527 developed dry AMD, and 242 developed wet AMD. Compared to individuals without AF, those with AF have a significantly higher risk of developing AMD (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.42-3.11), dry AMD (HR, 2.55; 95% CI, 2.12-3.07), wet AMD (HR, 2.50; 95% CI, 1.90-3.28), and ischemic stroke (HR, 1.67; 95% CI, 1.60-1.73). Across most subpopulations, AF is consistently linked to higher risks of both dry and wet AMD.<br><br>CONCLUSION: Individuals with AF experience a higher risk of developing both dry and wet forms of AMD compared to individuals without AF.},
}
@article {pmid41222201,
year = {2025},
author = {Beqiri, S and Pan, H and Kumar, BS and Berni, A and Shen, M and Hiya, FE and Cheng, Y and El-Mulki, OS and Herrera, G and Badla, O and Kastner, J and Trivizki, O and Di Nicola, M and O'Brien, RC and Waheed, NK and Wang, RK and Gregori, G and Rosenfeld, PJ},
title = {Changes in Choriocapillaris Flow Deficits Before and After the Onset of Large Choroidal Hypertransmission Defects in AMD.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {14},
pages = {20},
pmid = {41222201},
issn = {1552-5783},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Aged ; Fluorescein Angiography/methods ; Regional Blood Flow/physiology ; Aged, 80 and over ; *Macular Degeneration/physiopathology/diagnosis ; Capillaries/physiopathology ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; Follow-Up Studies ; Middle Aged ; Prospective Studies ; },
abstract = {PURPOSE: Eyes with intermediate age-related macular degeneration (iAMD) underwent swept-source optical coherence tomography angiography (SS-OCTA) imaging and were evaluated longitudinally to determine if choriocapillaris flow deficits (CCFDs) developed before or after the formation of large choroidal hypertransmission defects (hyperTDs).<br><br>METHODS: A retrospective review was performed of prospectively collected 6 &#xd7; 6-mm SS-OCTA images from eyes with iAMD that developed large hyperTDs, defined on en face images from subretinal pigment epithelium (sub-RPE) slabs positioned 64 to 400 &#xb5;m beneath Bruch's membrane (BM) as bright lesions with a greatest linear dimension (GLD) &#x2265; 250&#xa0;&#xb5;m. The onset of large hyperTDs was designated as baseline T = 0; additional visits were chosen at 1 year before and at two 1-year intervals after T = 0. A grid box strategy was implemented for the analysis of CCFDs at the site where hyperTDs formed. A change in the percentage of CCFDs greater than 5% was considered to be a true change outside the repeatability limits.<br><br>RESULTS: Twenty-seven targets from 27 eyes eligible for final analysis were followed over four visits separated by 12 &#xb1; 3 months. No targets showed a marked CCFD change above 5% prior to hyperTD onset. Only two targets showed marked increases in CCFDs after hyperTD formation. A grouped analysis of all targets showed no mean CCFD change prior to hyperTD onset, but a significant change only after the onset of hyperTD.<br><br>CONCLUSIONS: CCFD values did not increase prior to the onset of hyperTDs with increases in CCFDs detected after their onset. These results suggest that loss of choriocapillaris perfusion did not precede hyperTD formation but may play a role in hyperTD growth.},
}
@article {pmid41222198,
year = {2025},
author = {Cinque, F and de Breuk, A and Mhmud, H and De Jong, S and Vermeulen, J and Liefers, B and den Hollander, AI and Thee, E and Colijn, JM and Heesterbeek, TJ and Klaver, CC and Hoyng, CB and Lechanteur, YTE},
title = {Disease Progression in Age-Related Macular Degeneration Patients Carrying Rare Variants in the Complement Factor H or Complement Factor I Genes.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {14},
pages = {23},
pmid = {41222198},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Aged ; *Complement Factor H/genetics/metabolism ; Disease Progression ; *Complement Factor I/genetics/metabolism ; Retrospective Studies ; Visual Acuity/physiology ; Incidence ; *Macular Degeneration/genetics/epidemiology/diagnosis ; Follow-Up Studies ; Middle Aged ; Aged, 80 and over ; Prospective Studies ; Geographic Atrophy/genetics ; },
abstract = {PURPOSE: Rare variants in CFI and CFH genes are associated with AMD. This study aimed to compare the incidence of late AMD in carriers of these variants to a reference cohort using a long follow-up cohort (LF-cohort) and to examine short-term AMD progression in a short follow-up cohort (SF-cohort).<br><br>METHODS: This cohort study included two groups: the LF-cohort, observed for more than five years retrospectively and the SF-cohort, observed for one year prospectively, with patients attending in-hospital visits. One hundred twelve AMD patients with rare CFH/CFI or variants were invited from the European Genetic Database. The LF-cohort's outcome was the incidence of late AMD per 100 person-years compared to a matched reference cohort. In the SF-cohort, geographic atrophy (GA), retinal sensitivity, and visual acuity were measured.<br><br>RESULTS: The LF-cohort included 28 patients (median [interquartile range {IQR}
] age, 71.3 [24.3] years; 18 females [64%]) with an incidence rate of 6.2 per 100 person-years which was higher than the reference cohort (1.8 per 100 person years (P = 0.01)). The SF-cohort consisted of 44 patients (median [IQR] age 70.5 [16.5] years; 29 (65% female). Mean annual GA growth (SD) was 0.22 mm (0.13) in 19 eyes of 12 patients. Retinal sensitivity changed for late-staged eyes (right eye: 17.2 dB to 15.7 dB, P = 0.03; left eye 17.3 dB to 16.4 dB, P = 0.06) whereas visual acuity did not.<br><br>CONCLUSIONS: Carriers of rare CFI or CFH variants show a higher incidence of late AMD. These patients may benefit from personalized gene therapy and complement inhibition in future trials.},
}
@article {pmid41221122,
year = {2025},
author = {Alqahtani, HB and Votruba, M and Regini, J},
title = {Do retinal implants provide long-term efficacy, safety and improve quality of life? A systematic review.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414251385884},
pmid = {41221122},
issn = {2515-8414},
abstract = {BACKGROUND: Retinal implants have emerged as interventions to partially restore functional vision such as light perception, motion detection or object localisation in patients with severe vision loss from degenerative retinal conditions, including retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD).<br><br>OBJECTIVES: To evaluate the long-term efficacy, safety and quality of life (QoL) impact of retinal implants with &#x2a7e;1&#x2009;year of follow-up.<br><br>METHODS: Following PRISMA guidelines, a systematic search was conducted (31st July to 31st August 2024) in Web of Science, PubMed, Medline, Scopus, Cochrane Library and Embase, using the terms: ('retinal implant' OR 'retinal prosthesis') AND ('long-term' OR 'follow-up') AND ('efficacy' OR 'safety' OR 'quality of life'). No publication date restrictions were applied. Eligible studies were in English, involved human subjects with retinal degenerations, and reported &#x2a7e;1&#x2009;year follow-up. Risk of bias was assessed using the Critical Appraisal Skills Programme (CASP) cohort study checklist for most studies, as they involved prospective follow-up without randomisation or control groups. The Joanna Briggs Institute (JBI) critical appraisal checklist for case series was applied to studies with a case series design. Narrative synthesis was applied.<br><br>RESULTS: Thirteen studies met the inclusion criteria: 53.85% assessed epiretinal implants (Argus II), 30.77% subretinal (Alpha AMS and PRIMA), and 15.38% suprachoroidal (44 and 49-channel STS). Epiretinal implants improved visual function, with up to 89% better in SLT, 50%-56% in DOM, and 30%-40% reaching &#x2a7e;2.9 logMAR when activated. Subretinal implants enhanced light perception, localisation, and grating acuity (to 3.33 cycles/degree), with acuity of 20/460 and 20/550 in some cases. Suprachoroidal devices improved SLT, DOM and GVA. Adverse events were more frequent with epiretinal than other implant types. QoL outcomes improved, particularly in mobility, orientation, and daily tasks.<br><br>CONCLUSION: Retinal implants confer functional vision, but acuities remain below 20/200, and recipients continue to meet criteria for legal blindness. Given the high risk of bias, lack of controls and potential placebo effects, further high-quality evidence is needed to confirm their efficacy, safety and QoL impact.},
}
@article {pmid41219682,
year = {2025},
author = {de Angelis, L and Galasso, M and Di Simplicio, S and Raimondi, R and Vidal-Aroca, F and Romano, MR and Toro, MD and Rizzo, S and Barca, F},
title = {In Vivo Evaluation of SING IMT™ Alignment for Late-Stage Age-Related Macular Degeneration Using Anterior Segment OCT.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41219682},
issn = {2193-8245},
abstract = {INTRODUCTION: This study aimed to assess the in vivo positioning, tilt, and decentration of the second-generation implantable miniature telescope (SING-IMT™; Samsara Vision, Inc., Far Hills, NJ, USA) using swept-source anterior segment optical coherence tomography (AS-OCT).<br><br>METHODS: This was a multicentric retrospective observational study conducted at two tertiary referral centers (Palagi Hospital, Florence, Italy, and Royal Victoria Infirmary Hospital, Newcastle upon Tyne, UK). Eleven eyes from 11 patients with end-stage age-related macular degeneration (AMD) underwent secondary SING IMT&#x2122; implantation at these two tertiary centers. Using high-resolution AS-OCT (CASIA2 system [Tomey, Nagoya, Japan] and Anterion system [Heidelberg Engineering, Heidelberg, Germany]), telescope alignment was assessed after 12&#xa0;months. Decentration and tilt were calculated and reported in both Cartesian and polar coordinates. Telescope configuration relative to the iris plane and corneal-telescope (C-T) distance and endothelial cell count was also evaluated.<br><br>RESULTS: The mean (&#xb1; standard deviation) follow-up was&#xa0;15.7&#x2009;&#xb1;&#x2009;2.8&#xa0;months. The mean decentration was 0.33&#x2009;&#xb1;&#x2009;0.12&#xa0;mm, with a predominant superior and nasal displacement. Mean tilt was 3.28&#x2009;&#xb1;&#x2009;1.31&#xb0;, oriented mainly in the supero-temporal direction. Three positional configurations were observed: anterior to the iris plane (36.4%), at the iris plane (36.4%), and posterior to the iris plane (27.3%). The mean C-T distance was 2.71&#x2009;&#xb1;&#x2009;0.48&#xa0;mm. Mean endothelial cell loss at 12&#xa0;months was 13.21%&#x2009;&#xb1;&#x2009;3.57%.<br><br>CONCLUSIONS: After 12&#xa0;months of follow-up, the SING IMT&#x2122; maintained stable in-the-bag fixation, with tilt and decentration values within the ranges previously reported for conventional in-the-bag intraocular lenses.},
}
@article {pmid41219247,
year = {2025},
author = {Chiu, CJ and Chiu, ES and Chang, ML},
title = {Interaction between serum levels of Porphyromonas gingivalis immunoglobulin G and lutein/zeaxanthin is associated with risk for age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {39400},
pmid = {41219247},
issn = {2045-2322},
support = {R01 EY021826/EY/NEI NIH HHS/United States ; R21 EY028209/EY/NEI NIH HHS/United States ; RO1EY021826 and R21EY028209/GF/NIH HHS/United States ; },
mesh = {Humans ; *Porphyromonas gingivalis/immunology ; *Macular Degeneration/blood/microbiology/etiology ; Female ; Male ; *Immunoglobulin G/blood ; Middle Aged ; Case-Control Studies ; Aged ; Risk Factors ; Periodontitis/microbiology/blood ; Antibodies, Bacterial/blood ; Nutrition Surveys ; *Bacteroidaceae Infections/blood/microbiology ; },
abstract = {Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiota. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiota and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis. To investigate the potential association between periodontopathic microbiota and AMD occurrence, we conducted a candidate microbe approach case-control study in the Third National Health and Nutrition Examination Survey (NHANES-III). Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Consistent with current evidence that host nutritional status critically modulates immune responses to the microbiota and influences human health, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 µmol/L or ≥ 20 µg/dL) might potentially mitigate the P. gingivalis-related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrients related to eye health and humoral response to P. gingivalis.Significance statement: While humoral response to P. gingivalis indicates an impact on age-related macular degeneration, nutritional factors may modulate the associated risk.},
}
@article {pmid41218907,
year = {2025},
author = {Hong, Y and Bo, QY and Sun, XD},
title = {[Progress on predictive biomarkers for exudation in polypoidal choroidal vasculopathy].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {61},
number = {11},
pages = {915-920},
doi = {10.3760/cma.j.cn112142-20250416-00186},
pmid = {41218907},
issn = {0412-4081},
support = {U22A20311, 82301220, 82388101//National Natural Science Foundation of China/ ; 23YF1434100//"YangFan Program"of Shanghai Municipal Committee of Science and Technology/ ; 20224Y0352//Clinical research project of Shanghai Municipal Health Commission/ ; },
mesh = {Humans ; Biomarkers ; *Choroid/blood supply ; *Choroidal Neovascularization/diagnosis ; *Choroid Diseases/diagnosis ; Macular Degeneration ; Polypoidal Choroidal Vasculopathy ; },
abstract = {Polypoidal choroidal vasculopathy (PCV) is a common subtype of neovascular age-related macular degeneration (nAMD) in Asian populations. Clinical follow-up has revealed varying degrees of activity in PCV lesions. Studies have shown that multimodal retinal imaging techniques can be used to assess the activity of PCV lesions. Abnormal branching vascular networks, polypoidal lesions, and choroidal-related features are important biological markers for predicting lesion activity. Additionally, demographic characteristics and genetic traits of patients may also serve as relevant factors for assessing the activity of PCV lesions. This review summarizes recent updates in the understanding of PCV lesion activity based on multimodal retinal imaging studies and their impact on clinical ophthalmic practice. It also explores the potential applications and prospects of lesion activity characteristics in the treatment and follow-up of PCV, aiming to provide reference for clinicians in assessing and determining the activity of PCV lesions and developing personalized treatment and follow-up plans.},
}
@article {pmid41218596,
year = {2025},
author = {Debbarma, R and Dos Santos, ACF and Ramirez Gutierrez, D and Erk, KA and Koo, H and da Cunha, F and Ladisch, M},
title = {Imaging of Intra-Matrix IgG Diffusion as an Indicator of Age-Related Vitreous Changes.},
journal = {Molecular pharmaceutics},
volume = {22},
number = {12},
pages = {7445-7454},
doi = {10.1021/acs.molpharmaceut.5c00836},
pmid = {41218596},
issn = {1543-8392},
mesh = {*Immunoglobulin G/metabolism/chemistry ; *Vitreous Body/metabolism ; Hyaluronic Acid/chemistry/metabolism ; Humans ; Aged ; Viscosity ; Aged, 80 and over ; Animals ; Diffusion ; Cattle ; Macular Degeneration/drug therapy/metabolism ; Intravitreal Injections ; *Aging ; },
abstract = {Intravitreal injection of therapeutics that treat age-related macular degeneration and diabetic retinopathy requires diffusion of the protein therapeutic through hyaluronic acid (HA) in the vitreous humor. The tracking of bovine IgG movement in an in vitro HA matrix simulates protein diffusion in the vitreous humor and provides a fundamental understanding of the diffusion properties of injected IgG type biologics. Phase separation of the vitreous humor, creating pockets of liquid rich in HA, begins at about age 40 and steadily progresses, with more than 50% of the vitreous being liquid by age 80-90 years. When formulated to represent viscosity at the injection site for patients between 65 and 80 years old, the HA has a viscosity of 0.1 Pa s. The vitreous humor for patients at ages lower than 65 corresponds to a viscosity of 1 Pa s. This work shows how HA matrices may be formulated to simulate the HA environment in the vitreous humor so that IgG diffusion may be measured using label-free imaging based on tryptophan autofluorescence. A 37% increase in the mean diffusion coefficient occurred as the HA matrix viscosity decreased from 1 to 0.1 Pa s, thus indicating that protein formulations may need to be adjusted if equivalent diffusion rates are to be achieved in the vitreous humor of different ages of patients. This approach provides an in vitro preclinical screening tool that could prove useful for correlating the diffusion properties of protein therapeutics as a function of the viscoelasticity of the vitreous humor.},
}
@article {pmid41218567,
year = {2025},
author = {Cai, S and Liang, X and Wu, H and Li, X and Pu, Q},
title = {Navigating the ocular barrier: Viral- and nanotechnology-based delivery systems as promising therapeutic agents for ocular diseases.},
journal = {Molecular aspects of medicine},
volume = {106},
number = {},
pages = {101421},
doi = {10.1016/j.mam.2025.101421},
pmid = {41218567},
issn = {1872-9452},
abstract = {While the intricate and precisely specialized structure of the human eye is critical for its appropriate function, it also presents a number of anatomical and physiological barriers, such as tight junctions, enzymatic degradation, and dynamic fluid turnover, which highly restrict the intraocular bioavailability of various therapeutic compounds. This is more significant for those therapeutic compounds that are used for complications affecting the posterior segment. Accordingly, conventional therapeutic strategies for common ocular complications such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and infectious keratitis significantly demand invasive administration approaches and multiple injections, frequently resulting in various side effects and suboptimal therapeutic consequences. To address these major challenges, novel technologies, such as viral- and nanotechnology-based delivery systems, have provided emerging opportunities to bypass ocular barriers and facilitate targeted, maintained, and efficient drug and gene delivery. The present review aims to comprehensively describe the current advancements in both viral- and nanotechnology-based strategies for ocular diseases. It discusses the complex molecular structure and physiological functions of the ocular barriers, focusing on the exact mechanisms that restrict drug permeation. Moreover, this review describes the design principles, physicochemical properties, and therapeutic potential of diverse viral- and nanotechnology-based delivery systems. Their efficacy and safety profiles are thoroughly discussed across various pre-clinical and clinical studies. Furthermore, the review discusses the emergence of hybrid viral-nanotechnology delivery systems that combine the strengths of both approaches, offering enhanced targeting precision and biocompatibility. The major challenges linked to the clinical translation of these novel technologies, such as aspects of biocompatibility and immunogenicity are also addressed. This review highlights the significant transformative potential of viral vectors and nanotechnology in reforming ocular disease management and increasing patient quality of life.},
}
@article {pmid41218191,
year = {2025},
author = {Călugăru, D and Călugăru, M},
title = {Ten-year follow-up of patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004728},
pmid = {41218191},
issn = {1539-2864},
}
@article {pmid41217603,
year = {2025},
author = {Akada, M and Hata, M and Ideyama, M and Kido, A and Miyata, M and Tamura, H and Ooto, S and Tsujikawa, A},
title = {Subtype-specific shifts in age, axial length, and clinical profile of neovascular age-related macular degeneration: a five-year study in Japan.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41217603},
issn = {1613-2246},
abstract = {PURPOSE: To evaluate 5-year temporal changes in baseline clinical characteristics-age, axial length, and best-corrected visual acuity-among treatment-naïve eyes with neovascular Age-Related Macular Degenaration (nAMD), comparing pachychoroid neovasculopathy (PNV) with drusen-driven (non-PNV) nAMD at a Japanese tertiary center.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: Registry data from Kyoto University Hospital were analyzed for patients newly diagnosed with nAMD in 2013/2014 and in 2018/2019. Patients were classified as PNV or non-PNV based on findings derived from multimodal imaging-including optical coherence tomography, indocyanine-green angiography, and color fundus photography. Demographic data, axial length, best-corrected visual acuity (BCVA) at baseline and 1 year posttreatment, and the proportion of eyes achieving &#x2265;0.20 logMAR improvement were compared over time.<br><br>RESULTS: A total of 118 patients were included. In the non-PNV group, mean age rose from 74.35 &#xb1; 8.42 years to 77.39 &#xb1; 7.90 years (p = 0.021), whereas the PNV group showed a smaller, non-significant change from 68.88 &#xb1; 7.25 to 70.41 &#xb1; 9.19 years (p = 0.48). Among non-PNV cases, both mean age (p=0.021) and axial length (p=0.017) increased significantly over time. In contrast, PNV cases showed no significant changes in age or axial length. BCVA outcomes and the proportion of patients achieving &#x2265;0.20 logMAR improvement were similar across time points within each subtype. Multivariable logistic regression analysis revealed no significant associations between visual improvement and year, subtype, age, or axial length.<br><br>CONCLUSIONS: This study revealed an aging trend and axial elongation among non-PNV cases over time, underscoring a subtype-specific divergence in clinical trajectory.},
}
@article {pmid41216998,
year = {2025},
author = {Brouwer, NJ and Vu, THK and De Jong‐Hesse, Y and van Dijk, EHC},
title = {The prechoroidal cleft in neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70035},
pmid = {41216998},
issn = {1755-3768},
abstract = {The prechoroidal cleft is a lenticular, hypo-reflective space on optical coherence tomography imaging, located between a band of fibrovascular material underneath the retinal pigment epithelium (RPE) and Bruch's membrane. It occurs in 8%-22% of neovascular age-related macular degeneration (nAMD) eyes, most often with macular neovascularization (MNV) type 1 and 3, and less often with MNV type 2 or polypoidal choroidal vasculopathy. The presence of a prechoroidal cleft is associated with poor visual prognosis, some studies report more frequent occurrence of RPE tears and subretinal haemorrhages. Eyes with a prechoroidal cleft require more frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections to treat the nAMD and more often require a switch to other anti-VEGF medication. Clinicians should be aware of the prechoroidal cleft for diagnostic and prognostic reasons, as it may be misunderstood for other (subretinal) fluid or even a choroidal lesion.},
}
@article {pmid41216067,
year = {2025},
author = {Moafa, MA and Albahrawy, SS and Alluwimi, MS and Alrasheed, S and Elmadina, AM and Mutwaly, RF and Abdelhamid, AF and Albarnawi, EH and Alghamdi, WM and Aldebasi, YH},
title = {Assessment of Peripapillary Retinal Nerve Fibre Layer Thickness, Optic Nerve Head Rim Area, Anterior Chamber Parameters, and Axial Length in Myopic Eyes.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e94271},
pmid = {41216067},
issn = {2168-8184},
abstract = {BACKGROUND: Myopic eyes commonly show structural changes, including optic nerve head (ONH) and altered anterior chamber parameters.<br><br>AIM: The study aimed to investigate the associations of peripapillary retinal nerve fibre layer (RNFL) thickness, optic disc rim area, anterior chamber parameters, and axial length in myopic eyes.<br><br>METHODS: This&#xa0;cross-sectional study was conducted at the Royal Commission Medical Centre, Yanbu, Saudi Arabia, between February and May 2025 and included 152 myopic eyes. Refraction was measured using an autorefractometer. Swept-source optical coherence tomography (SS-OCT)&#xa0;scans (optic disc cube 200&#x2009;&#xd7;&#x2009;200) were used to assess peripapillary RNFL thickness and optic disc rim area. Corneal and anterior chamber parameters, along with axial length, were measured using Pentacam AXL (OCULUS Optikger&#xe4;te GmbH, Wetzlar, Germany). Data analysis was conducted to assess the correlation between myopia severity and structural ocular changes.<br><br>RESULTS: Myopic eyes (mean spherical equivalent: -2.02 &#xb1; 1.34 D) showed a significant inverse correlation with both central corneal thickness (r = -0.193, P < 0.05) and corneal thickness at the thinnest point (r = -0.225, P < 0.05). Anterior chamber volume (r = 0.266, P < 0.001) and anterior chamber depth (r = 0.259, P < 0.001) showed significant positive correlations with myopia, while the anterior chamber angle showed no significant association (P > 0.05). Axial length was strongly correlated with myopia severity (r = 0.545, P < 0.001). Inverse correlations were observed between myopia and both peripapillary RNFL thickness (r = -0.100, P > 0.05) and ONH rim area (r = -0.134, P > 0.05). A statistically significant inverse correlation was found between peripapillary RNFL thickness and axial length (r = -0.163, P < 0.05), as well as between ONH rim area and axial length (r = -0.167, P < 0.05).<br><br>CONCLUSION: The study revealed a significant positive correlation between myopia and both anterior chamber volume and anterior chamber depth, while the anterior chamber angle remained unaffected. The increase in myopia severity was correlated with thinning of the peripapillary RNFL and a reduction in ONH rim area. These findings underscore the importance of assessing axial elongation and structural changes in myopic eyes, particularly in the context of ocular diseases such as glaucoma, myopic macular degeneration, and retinal detachment.},
}
@article {pmid41212222,
year = {2025},
author = {Honjo, J and Mukai, R and Itagaki, K and Tanaka, K and Norikawa, K and Kato, Y and Kasai, A and Sekiryu, T},
title = {A one-year study on the regression effects of aflibercept and faricimab on retinal pigment epithelial detachment.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41212222},
issn = {1435-702X},
abstract = {PURPOSE: To compare long-term regressive effects on pigment epithelial detachment (PED) between aflibercept and faricimab in type 1 macular neovascularization (MNV).<br><br>METHODS: We analyzed 94 eyes from 92 patients diagnosed with type 1 MNV using multimodal imaging. Seventy-one eyes received intravitreal aflibercept injections (IVA group), and 23 received intravitreal faricimab injections (IVFa group). After three consecutive monthly injections, intervals were adjusted in 2-4 week increments within drug-specific windows (IVA, 4-12 weeks; IVFa, 8-16 weeks) through 1 year. The maximum height (MH) and horizontal maximum diameter (H-MD) of PED were measured using optical coherence tomography before treatment and at 3 months and 1year post-treatment. We also assessed associations between PED change and 1-year dry macula, and explored visual outcomes with using analysis of covariance and logistic models.<br><br>RESULTS: MH decreased in both IVA (184&#x2009;&#xb1;&#x2009;176&#x2192;126&#x2009;&#xb1;&#x2009;153&#xa0;&#x3bc;m at 3 months, P&#x2009;=&#x2009;0.0003; 124&#x2009;&#xb1;&#x2009;135&#xa0;&#x3bc;m at 1 year, P&#x2009;=&#x2009;0.0005) and IVFa (162&#x2009;&#xb1;&#x2009;124&#x2192;83&#x2009;&#xb1;&#x2009;65&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.0056; 86&#x2009;&#xb1;&#x2009;71&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.0053). The mean change in MH was not significantly different between groups (P&#x2009;=&#x2009;0.244). H-MD did not show significant regression in either group. IVFa required fewer injections (6.17&#x2009;&#xb1;&#x2009;0.39 vs. 7.90&#x2009;&#xb1;&#x2009;1.99/year; P&#x2009;<&#x2009;0.0001) and achieved a longer final intended injection interval (14.17&#x2009;&#xb1;&#x2009;2.53 vs. 8.64&#x2009;&#xb1;&#x2009;2.90 weeks; P&#x2009;<&#x2009;0.0001). In multivariable linear regression for percent MH change at 1 year, annual injection number was positively associated with percent change (&#x3b2;&#x2009;=&#x2009;7.62% points/injection, P&#x2009;=&#x2009;0.012), whereas drug type was not (P&#x2009;=&#x2009;0.633), adjusting for baseline MH (&#x3b2; = -0.078/&#xb5;m, P&#x2009;=&#x2009;0.016; all VIFs&#x2009;<&#x2009;2). At 1 year, MH was lower in dry vs. wet macula (90&#x2009;&#xb1;&#x2009;82 vs. 186&#x2009;&#xb1;&#x2009;185&#xa0;&#x3bc;m; P&#x2009;=&#x2009;0.0004). For vision, &#x2265; 0.2logMAR gain was predicted by CMT decrease (OR&#x2009;&#x2248;&#x2009;1.56 per 100&#xa0;&#x3bc;m decrease; P&#x2009;=&#x2009;0.045), while percent PED change was not significant (P&#x2009;=&#x2009;0.283).<br><br>CONCLUSION: In a treat-and-extend regimen with different label constraints, 1-year PED regression was similar for IVA and IVFa and was achieved with less treatment burden in IVFa. PED regression aligned with dry macula rather than with large visual gains, which instead tracked with retinal thickness recovery.},
}
@article {pmid41211376,
year = {2025},
author = {Kong, H and Feng, H and Wang, H},
title = {Global burden of age-related macular degeneration (1990-2021): trends, age-sex disparities, and socioeconomic dynamics from the GBD study.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1594672},
pmid = {41211376},
issn = {2296-2565},
mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; Female ; Aged ; Prevalence ; *Global Burden of Disease/trends ; Middle Aged ; *Global Health/statistics &amp; numerical data ; Socioeconomic Factors ; Aged, 80 and over ; Risk Factors ; Adult ; Sex Factors ; *Health Status Disparities ; },
abstract = {OBJECTIVES: This study aimed to assess the global burden of Age-related macular degeneration (AMD) across countries, regions, and age groups by sex, sociodemographic index (SDI) level, and risk factors from 1990 to 2021, using newly updated data from the Global Burden of Disease (GBD) study. The focus was on age-related disparities in AMD burden by sex and SDI.<br><br>METHODS: This population-based study utilized AMD data from GBD 2021 (1990-2021). The burden was evaluated using the number of cases, prevalence rates per 100,000 population, and trends in years lived with disability (YLDs) and prevalence, assessed through average annual percentage changes (AAPCs) and estimated annual percentage changes (EAPCs).<br><br>RESULTS: Globally, AMD prevalence increased from 364,000 cases in 1990 to 806,000 in 2021 (+121%), while YLDs rose from 30,000 to 58,000 (+91%). However, age standardized prevalence and YLD rates (ASPRs and ASYRs) significantly declined (EAPCs: -0.26 and -0.94, respectively). Regional analyses revealed that low SDI regions (e.g., sub-Saharan Africa) bore the highest AMD burden (ASPR: 139.9 per 100,000) and exhibited a younger age distribution, with a significantly higher proportion of cases in individuals aged 55-74&#x202f;years. In contrast, high SDI regions (e.g., high-income Asia-Pacific) had a concentration of cases among those aged 70&#x202f;years or older. While medium SDI regions accounted for one-third of global cases in 2021, age-standardized rates declined most slowly in low SDI regions (EAPC: -1.03) and even trended upward in some countries. AMD cases peaked globally at ages 65-69, yet prevalence was highest among those over 85&#x202f;years (1,349.9 per 100,000), with women generally experiencing a higher burden than men. These findings highlight distinct regional patterns, with younger disease profiles in low SDI regions and aging-driven increases in high SDI regions, underscoring the need for targeted prevention and control strategies.<br><br>CONCLUSION: Although global efforts over the past 30&#x202f;years have led to a decline in AMD prevalence rates and YLDs, the absolute number of cases and YLDs continues to rise, driven by age, sex, socioeconomic status, and geographic location. These findings provide an epidemiological basis for developing global public health strategies to address these ongoing challenges.},
}
@article {pmid41211298,
year = {2026},
author = {Bai, ZP and Pan, YS and Cai, YX and Chen, C and Tao, D and Zhao, XY and Shen, YF and Chen, F and Li, JH and Qu, J and Huang, XF},
title = {Investigating the Shared Genetic Architecture of 3 Age-Related Ocular Disorders.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100942},
pmid = {41211298},
issn = {2666-9145},
abstract = {PURPOSE: To explore the shared genetic architecture, causal relationships, and cell type-specific expression patterns of pleiotropic genes in age-related macular degeneration (AMD), cataract, and primary open-angle glaucoma (POAG), uncovering molecular mechanisms and informing targeted therapies.<br><br>DESIGN: A genetic association study combined with cross-trait meta-analyses, Mendelian randomization analyses, and single-cell RNA sequencing (scRNA-seq) analysis.<br><br>SUBJECTS: The data related to 3 age-related ocular diseases, including AMD, cataract, and POAG, were obtained from publicly available genome-wide association study (GWAS) databases.<br><br>METHODS: We conducted a comprehensive genetic analysis utilizing GWAS summary statistics to examine genetic correlations among AMD, cataract, and POAG. Cross-trait meta-analyses were performed to identify shared risk loci. Mendelian randomization was employed to investigate potential causal relationships between these conditions. Additionally, we analyzed scRNA-seq data to examine the expression patterns of identified pleiotropic genes across different retinal cell types.<br><br>MAIN OUTCOME MEASURES: Identification of shared risk single nucleotide polymorphisms (SNPs) and pleiotropic loci. Causal relationships between AMD, cataract, and POAG. Cell type-specific expression patterns of pleiotropic genes in retinal cells.<br><br>RESULTS: Our analysis revealed significant genetic correlations, with a negative correlation between AMD and POAG and a positive correlation between cataract and POAG. Cross-trait meta-analyses identified shared risk SNPs, with CDKN2B-AS1 emerging as a notable pleiotropic locus. Mendelian randomization analyses suggested causal relationships between AMD and cataract, as well as between POAG and AMD. Single-cell expression analysis demonstrated cell type-specific expression patterns of pleiotropic genes including ATXN2, HTRA1, SIX6, and THSD7A across retinal cells.<br><br>CONCLUSIONS: This study provides compelling evidence for shared genetic architecture and causal relationships among AMD, cataract, and POAG. The identification of specific pleiotropic genes and their expression patterns across retinal cell types offers new insights into the molecular mechanisms underlying these age-related ocular diseases, potentially informing the development of targeted therapeutic strategies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41208951,
year = {2025},
author = {Adrean, SD and Hill, L and Amador-Patarroyo, J},
title = {Fibrosis in Patients With Choroidal Neovascularization Based on Spectral-Domain Optical Coherence Tomography: Findings From the HARBOR Trial.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251389993},
pmid = {41208951},
issn = {2474-1272},
abstract = {Purpose: To evaluate the rate and impact of fibrosis on visual outcomes by choroidal neovascularization (CNV) type, based on spectral-domain optical coherence tomography (SD-OCT), in patients with neovascular age-related macular degeneration (nAMD). Methods: Fibrosis status and location at month 24, stratified by baseline CNV type, were evaluated using data from the HARBOR trial (NCT00891735). All patients (n = 1097) received pro re nata or monthly ranibizumab treatment. Results: Fibrosis was most common in eyes with type 2 CNV lesions (53%) compared with other types (type 1, 31%; mixed type 1 or 2, 45%; any type 3, 33%; P < .0001). The rate of fibrosis differed by less than or equal to 6% between monthly and pro re nata treatment regimens. In eyes with subretinal fibrosis, most (65% to 78%) showed subfoveal involvement at month 24. Mean visual acuity gains at month 24 were not negatively affected by the presence of fibrosis (type 1, 8.0 letters; type 2, 11.0; mixed type 1 or 2, 7.8; any type 3, 16.2), regardless of treatment regimen. Male sex and current smoking status were associated with significantly higher rates of fibrosis at month 24 (P < .0001 and P = .003, respectively). Conclusions: Many patients with nAMD develop fibrosis despite antivascular endothelial growth factor therapy, and the prevalence of fibrosis is affected by baseline CNV type.},
}
@article {pmid41205855,
year = {2025},
author = {Chen, Y and Jiang, F and Fu, Y and Han, N and Yang, J and Wu, X and Mao, T and Zhang, M},
title = {Transketolase regulates endoplasmic reticulum stress independent of enzymatic activity in human retinal Müller cells.},
journal = {Experimental eye research},
volume = {262},
number = {},
pages = {110732},
doi = {10.1016/j.exer.2025.110732},
pmid = {41205855},
issn = {1096-0007},
abstract = {Transketolase (TKT) expression in the nucleus of the retina has been reported, but its function beyond metabolism remains unclear. In this study, we investigated the role of TKT in the regulation of endoplasmic reticulum (ER) stress in the retina. Using a VEGF-overexpressing mouse model of age-related macular degeneration (AMD), we analyzed the expression and enzymatic activity of Tkt, and found that while expression levels remained unchanged, enzymatic activity was significantly reduced. Tkt localized primarily to the nucleus of the inner nuclear layer in healthy retinae but shifted outside the nuclear center in the lesion area of the AMD mouse model. ChIP-seq analysis revealed that Tkt-targeted genes were enriched in pathways related to metabolism, ER protein processing, and neurogenerative diseases. Among these targets, TKT directly bound to the promoter region of endoplasmic reticulum to nucleus signaling 1 (ERN1) and suppressed its expression, as validated by dual-luciferase reporter assays. In human Müller cells, TKT knockdown elevated ERN1 levels and exacerbated ER stress responses, while enzymatic inhibition alone had no effect on ER stress. Furthermore, TKT knockdown did not alter mitochondria respiration or glycolysis. These findings demonstrate that TKT mitigates ER stress in the human retinal Müller cells by transcriptionally regulating ERN1 in a manner that is independent of its enzymatic activity.},
}
@article {pmid41205703,
year = {2025},
author = {Yin, Q and Xie, Y and Chen, R and Lyu, Y and Yao, K and Han, H and Shentu, X},
title = {Multifunctional macrophage membrane biomimetic nanoparticles for targeted therapy of neovascular age-related macular degeneration.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {388},
number = {Pt 2},
pages = {114394},
doi = {10.1016/j.jconrel.2025.114394},
pmid = {41205703},
issn = {1873-4995},
mesh = {Animals ; *Macular Degeneration/drug therapy/pathology ; *Nanoparticles/administration &amp; dosage/chemistry ; *Choroidal Neovascularization/drug therapy/pathology ; *Biomimetic Materials/administration &amp; dosage/chemistry ; Mice, Inbred C57BL ; *Macrophages/metabolism ; Mice ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; *Curcumin/administration &amp; dosage/therapeutic use/chemistry ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Humans ; Male ; *Anti-Inflammatory Agents/administration &amp; dosage/therapeutic use ; Oxidative Stress/drug effects ; Antioxidants/administration &amp; dosage ; Disease Models, Animal ; },
abstract = {Neovascular age-related macular degeneration (nAMD), characterized by choroidal neovascularization (CNV), is a major cause of blindness worldwide. Current anti-vascular endothelial growth factor (VEGF) therapy remains unsatisfactory, as this single-target treatment only alleviates the symptoms without addressing the underlying etiology. Emerging research indicates that inflammation and oxidative stress are closely related to early nAMD, where the retinal pigment epithelium (RPE) is initially impaired, leading to pathological angiogenesis. Herein, biomimetic nanoparticles (termed SHP/Cur@MNPs) are prepared by co-encapsulating SHP099, an anti-inflammatory and anti-angiogenic agent, and curcumin, an antioxidant, into poly (lactic-co-glycolic acid) (PLGA) coated with macrophage membrane. Taking advantage of the macrophage-inherited property, SHP/Cur@MNPs effectively targeted the inflamed foci, specifically the vascular endothelium. Using a laser-induced CNV mouse model, SHP/Cur@MNPs markedly inhibited neovascularization, reduced inflammation and oxidative stress, and improved retinal function. Furthermore, bioinformatics analysis explored the mechanism of the Hippo signaling pathway in the treatment of SHP/Cur@MNPs against nAMD. Collectively, our study describes a strategy using biomimetic nanoparticles to achieve the synergistic effect by targeting major risk factors associated with nAMD, which might be a novel approach for the safe and effective treatment of nAMD.},
}
@article {pmid41205411,
year = {2025},
author = {Realini, G and Amato, R and Rasa, M and Ceccatelli, R and Cannavale, A and Bottoni, L and Marchini, F and Minetti, A and Giustarini, D and Canovai, A and Melecchi, A and Elia, I and Krepelova, A and Annunziata, F and Cammalleri, M and Rossi, R and Tosi, GM and Orlandini, M and Chiariello, M and Neri, F and Dal Monte, M and Galvagni, F},
title = {N-acetyl-l-cysteine ethyl ester (NACET) induces the transcription factor NRF2 and prevents retinal aging and diabetic retinopathy.},
journal = {Redox biology},
volume = {88},
number = {},
pages = {103914},
doi = {10.1016/j.redox.2025.103914},
pmid = {41205411},
issn = {2213-2317},
abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are leading causes of visual impairment in older people, with oxidative stress playing a central role in the development of these diseases. In this study, we showed that N-acetylcysteine ethyl ester (NACET) not only increases intracellular cysteine and glutathione levels, but also strongly stimulates the expression and activity of the transcription factor NRF2, a master regulator of oxidative stress response, in RPE cells. Using RNA interference, mass spectrometry and mutagenesis of the NRF2 regulator KEAP1, we identified direct cysteinylation of the sensor residues Cys226 and Cys613 on KEAP1 as the molecular mechanism underlying NRF2 activation after NACET treatment. Furthermore, we demonstrated that oral administration of NACET induces NRF2 activity in the retina in vivo, attenuates retinal aging hallmarks, and prevents diabetes-induced retinal neurodegeneration in mouse models. These results position NACET as a promising therapeutic candidate for age- and oxidative stress-related retinal diseases such as AMD and DR.},
}
@article {pmid41204997,
year = {2025},
author = {Gandhi, P and Sadeghi, E and Schulman, A and Singh, SR and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J},
title = {Correlation of drusen burden and vascular integrity in age-related macular degeneration using three-dimensional choroidal vascular model.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41204997},
issn = {1435-702X},
support = {NIH Core Grant P30 EY08098//Eye and Ear Foundation of Pittsburgh/ ; },
abstract = {PURPOSE: To study intricate relationship between drusen volume and evolving dynamics of retinal and choroidal vasculature in dry age-related macular degeneration (AMD).<br><br>METHODS: Patients underwent swept-source optical coherence tomography angiography (SS-OCTA) using Plex Elite 9000 device. Retinal thickness, retinal vessel perfusion, drusen volume, choroidal thickness (ChT), choroidal vascularity index (CVI), choroidal vessel diameters (MChVD), and intervessel distance (IVD) were assessed. The Advanced Research and Innovation (ARI) Network, ResUNet model, and Phansalkar thresholding were utilized for image analysis. The linear mixing model was used for the statistical analysis.<br><br>RESULTS: We assessed 53 eyes from 40 patients with dry AMD (22 eyes with early-stage, 31 eyes with intermediate-stage eyes). The mean age was 75.25 years and 62.5% were females. The mean LogMar visual acuity was 0.09&#x2009;&#xb1;&#x2009;0.17 standard deviation (SD) in early-stage and 0.19&#x2009;&#xb1;&#x2009;0.14 SD in intermediate-stage (p&#x2009;=&#x2009;0.03). Mean drusen volume was 0.075&#x2009;&#xb1;&#x2009;0.125 SD mm[3] in early-stage and 0.24&#x2009;&#xb1;&#x2009;0.26 SD mm[3] in intermediate-stage (p&#x2009;=&#x2009;0.005). Mean ChT was thicker, and mean CVI was higher in the early-stage compared to the intermediate-stage (p&#x2009;<&#x2009;0.05). A decrease of 11.48&#xa0;&#x3bc;m in MChVD for every 1&#xa0;mm&#xb3; increase in drusen volume was noted.<br><br>CONCLUSION: With increase in drusen volume, a reduction in CVI and MChVD was noted, without any significant association with changes in retinal metrics, suggesting that choroidal vessels may exhibit early changes during disease progression.},
}
@article {pmid41202799,
year = {2025},
author = {Ryals, RC},
title = {RPE replacement therapy for dry AMD-early success in a phase 1/2 clinical trial.},
journal = {Cell stem cell},
volume = {32},
number = {11},
pages = {1637-1638},
doi = {10.1016/j.stem.2025.10.007},
pmid = {41202799},
issn = {1875-9777},
mesh = {Humans ; *Retinal Pigment Epithelium/transplantation/cytology ; *Macular Degeneration/therapy ; *Stem Cell Transplantation ; Clinical Trials, Phase I as Topic ; },
abstract = {The number of retinal pigment epithelium (RPE) transplantation clinical trials for dry age-related macular degeneration (AMD) is increasing quickly, with groups using different stem cell sources, delivery approaches, and immune suppression. We discuss the recent success in a phase 1/2a clinical trial[1] evaluating allogeneic RPE stem cell-derived RPE cells isolated from the RPE layer of human cadaveric eyes.},
}
@article {pmid41201702,
year = {2025},
author = {Zhou, Y and Liu, J and Wang, Z and Huang, C and Wang, Q and Yu, X and Dai, C and Zhao, D and Cai, Y and Wang, T},
title = {Biological aging phenotypes mediate gut microbiota effects on age-related macular degeneration subtype progression: genetic causality by mendelian randomization and mediation analysis.},
journal = {AMB Express},
volume = {15},
number = {1},
pages = {167},
pmid = {41201702},
issn = {2191-0855},
support = {62175156//National Natural Science Foundation of China/ ; 22S31903000//Science and technology innovation project of Shanghai Science and Technology Commission/ ; 2025M771943//China Postdoctoral Science Foundation/ ; 2024409//Shanghai Post-doctoral Excellence Program/ ; 2023030716//Ningbo Top Medical and Health Research Program/ ; },
abstract = {The mechanisms driving age-related macular degeneration (AMD) progression into two major but distinct vision-threatening subtypes, geographic atrophy (GA) and choroidal neovascularization (CNV), are unclear. This study identifies causal gut microbiota (GM) taxa involved in AMD and their connections to biological aging phenotypes, including epigenetic clock acceleration, telomere length, mitochondrial DNA copy number, 731 immune cell traits, and 91 inflammatory proteins through genetic prediction. Analyzing 207 GM taxa and 205 functional pathways alongside AMD progression GWAS data, we found that class_Gammaproteobacteria significantly influences both CNV and GA, and a bidirectional gut-retina axis involving Erysipelotrichaceae was also identified. Genus_Flavonifractor, species_Ruminococcus_obeum, and species_Streptococcus_thermophilus may attenuate AMD progression. Mediation analysis revealed pathways linking Ruminococcus obeum to GA progression via SSC-A expression on CD4 + T cells, and a CNV-associated pathway mediated by CD33dim HLA-DR + CD11b- cell counts. This study provides novel genetic evidence linking GM to dynamic AMD progression, offering genetic insights for future experimental research and clinical strategies.},
}
@article {pmid41200258,
year = {2025},
author = {Rizwan Khan, AY and Malik, MB},
title = {Artificial Intelligence in Ophthalmology: Practical Applications, Subspecialty Evidence and Real-World Deployment.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {e96121},
pmid = {41200258},
issn = {2168-8184},
abstract = {Artificial Intelligence (AI) has undoubtedly emerged as a transformative technology in the field of medicine. In ophthalmology, it has been a catalyst for innovation in the methods used for the diagnosis, management, and treatment of different eye diseases. This article offers a detailed review of the literature on the application and utilization of AI technology in the field of ophthalmology. A detailed search of available literature on the use of AI in the field of ophthalmology was performed through the PubMed database and Google Scholar. Published literature on the role of AI in screening, diagnosis, and management of common ocular conditions such as diabetic retinopathy (DR), cataract, glaucoma, and age-related macular degeneration (AMD) was reviewed. Special emphasis was laid on the effectiveness and limitations of the recently developed AI systems for the detection and management of ocular conditions. We screened (n=4449) records and included (n=102) studies spanning retina, glaucoma, cornea, pediatric ophthalmology, neuro-ophthalmology, ocular oncology, surgery, emergencies, and tele-ophthalmology. Deep learning (DL) and machine learning (ML) algorithms have demonstrated significant performance in the analysis of ophthalmic data, including optical coherence tomography scans and retinal images, for accurately diagnosing and classifying diseases, predicting disease progression, and personalizing different treatment plans. In addition to the common ocular conditions, the use of AI has now spread to other domains of ophthalmology, such as pediatric ophthalmology, oculoplastics and reconstructive surgery, and triage and management of emergency ocular conditions. Various AI systems have shown accuracy similar to that of clinical experts, with the additional benefit of being less subjective and time-consuming. Despite significant progress, different challenges related to regulatory approval, standardization, data quality, and ethical considerations hamper the wide-scale implementation of AI in ophthalmology. Literature is evident on the transformative role of AI in screening, diagnosis, and management of various ocular conditions. However, currently, there are various challenges and limitations to the implementation of AI. Future research should focus on addressing these challenges while optimizing the utilization of AI algorithms for enhancing patient care in ophthalmology.},
}
@article {pmid41199318,
year = {2025},
author = {Lennikov, A and Yang, M and Elzaridi, F and Shu, DY and Hu, Z and Miller, WP and Tsonas, M and Huang, L and Yen, C and Chang, K and Chen, J and Vijikumar, A and Ashok, A and Cho, KS and Geniez, MS and Dartt, DA and Chen, DF},
title = {Non-invasive bioelectrical therapy suppresses retinal neovascularization by modulating cellular metabolism and inflammation.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {479},
pmid = {41199318},
issn = {1478-811X},
support = {HT9425-24-1-0788//U.S. Department of Defense/ ; M2021010F//BrightFocus Foundation/ ; R01EY019470/EY/NEI NIH HHS/United States ; R01 EY031696/EY/NEI NIH HHS/United States ; R01EY031696/EY/NEI NIH HHS/United States ; HT9425-23-1-1045//U.S. Department of Defense/ ; R01 EY019470/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; Microglia/metabolism ; *Retinal Neovascularization/therapy/pathology/metabolism ; *Electric Stimulation Therapy ; *Inflammation/pathology/therapy/metabolism ; Mice, Inbred C57BL ; Choroidal Neovascularization/therapy/pathology ; Endothelial Cells/metabolism ; Diabetic Retinopathy/therapy/pathology/metabolism ; Adenosine Triphosphate/metabolism ; Male ; Membrane Potential, Mitochondrial ; Retina/pathology ; },
abstract = {BACKGROUND: Pathological retinal neovascularization, a major cause of blindness, occurs in conditions such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Microglial activation and chronic neuroinflammation play critical roles in disease progression by promoting vascular permeability and angiogenesis. While anti-VEGF therapies are the current standard of care, their efficacy is limited, requiring frequent intraocular injections and raising concerns about long-term retinal health. Noninvasive transpalpebral electrical stimulation (TpES) has emerged as a potential alternative therapy, but its mechanism and therapeutic impact remain poorly understood.<br><br>METHODS: To investigate the therapeutic effects of TpES, we applied daily microcurrent stimulation (300 &#xb5;A, 20&#xa0;Hz, 4&#xa0;min) in laser-induced choroidal neovascularization (CNV) and streptozotocin (STZ)-induced DR mouse models. Vascular pathology was assessed using fluorescein angiography, optical coherence tomography (OCT), and immunohistochemistry. Mechanistic studies were conducted using primary microglia and human retinal endothelial cells (HREC) to evaluate TpES-induced changes in intracellular calcium ([Ca&#xb2;&#x207a;]i) signaling, mitochondrial membrane potential, and ATP production. Additionally, human RPE/choroidal explants from healthy, AMD, and DR donors were cultured to assess TpES effects on angiogenesis in healthy and pathological human tissues.<br><br>RESULTS: TpES significantly reduced vascular leakage (by ~&#x2009;30%, p&#x2009;<&#x2009;0.001) and lesion size in the CNV model (p&#x2009;<&#x2009;0.05), while also suppressing microglial infiltration and VEGF-A expression. In the DR model, TpES attenuated microaneurysm formation, preserved endothelial tight junctions (in vitro). Mechanistic studies revealed that TpES suppressed ATP-induced microglial activation by reducing mitochondrial membrane potential and intracellular ATP levels, leading to depletion of ER calcium stores and inhibition of proinflammatory and proangiogenic signaling. TpES also directly suppressed endothelial cell migration and tube formation, as well as angiogenic sprouting in human RPE/choroidal explants.<br><br>CONCLUSIONS: These findings establish TpES as a dual-action therapy that mitigates both inflammation and pathological angiogenesis by modulating microglial and endothelial metabolism. Given its noninvasive nature and ability to target key pathways in retinal pathology, TpES represents a promising therapeutic strategy for AMD, DR, and other retinal vascular diseases.},
}
@article {pmid41199263,
year = {2025},
author = {Menghini, M and Grimaldi, G and Paris, A and Bachmann, LM and Schmid, MK},
title = {One-year clinical outcomes of four-dose induction versus immediate treat-and-extend faricimab regimens in pretreated neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {624},
pmid = {41199263},
issn = {1471-2415},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Intravitreal Injections ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Aged, 80 and over ; Treatment Outcome ; Dose-Response Relationship, Drug ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Time Factors ; Antibodies, Bispecific ; },
abstract = {BACKGROUND/OBJECTIVES: This study aimed to compare one-year clinical outcomes of two faricimab treatment strategies in patients with previously treated exudative neovascular age-related macular degeneration (nAMD): (1) immediate switch to treat-and-extend dosing (T&amp;E), and (2) initiation with a four-dose induction ("loading") regimen.<br><br>SUBJECT/METHODS: Retrospective comparing two cohorts of pretreated nAMD patients with 12 months of follow-up who were either switched to Faricimab with immediate T&amp;E dosing (Lucerne protocol, "on-the-fly"), or initiated with a four-dose induction phase (Lugano protocol,"re-loading"). Both cohorts were subsequently managed according to a T&amp;E regimen. Demographic and clinical data, including prior intravitreal agents, best-corrected visual acuity (BCVA), central subfield thickness (CST) on optical coherence tomography (OCT), and length of treatment intervals were analysed. Multivariable models were adjusted for baseline differences.<br><br>RESULTS: Both cohorts (Lucerne, 183 eyes; Lugano, 33 eyes) were similar in baseline characteristics. BCVA improved by 0.81 ETDRS letters in Lucerne and by 2.42 in the Lugano cohort (p&#x2009;=&#x2009;0.250). CRT decreased by -38.3&#xa0;&#x3bc;m in Lucerne and by -57.8&#xa0;&#x3bc;m in Lugano (p&#x2009;=&#x2009;0.053). Treatment intervals increased by 2.2 weeks in Lucerne and 3.4 weeks in Lugano (p&#x2009;=&#x2009;0.092). At 12 months, 15.3% of Lucerne patients and 27.3% of Lugano patients achieved intervals&#x2009;&#x2265;&#x2009;12 weeks, with significantly higher odds of extension in Lugano (OR 3.87; p&#x2009;=&#x2009;0.013).<br><br>CONCLUSIONS: Both cohorts showed anatomical and functional improvements after switching to faricimab. The Lugano cohort, using a four-dose induction phase, showed longer treatment intervals, suggesting better disease stability.<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid41198979,
year = {2025},
author = {Feo, A and Boscia, G and Borrelli, E and Quarta, A and Stradiotto, E and Forte, P and Viggiano, P and Popovic, MM and Corradetti, G and Savastano, A and Boscia, F and Sarraf, D and Sadda, SR and Romano, MR},
title = {Vitelliform lesions and choroidal changes in chorioretinal disorders: pathophysiological insights and clinical implications.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41198979},
issn = {1476-5454},
abstract = {This narrative review aims to explore the correlation between choroidal thickness (CT), broader choroidal changes, and the development and progression of vitelliform lesions, with a focus on their potential modulatory role-whether primary or secondary- through mechanisms involving choriocapillaris (CC) and retinal pigment epithelium (RPE) dysfunction. CT was found to be significantly increased in various vitelliform maculopathies, including adult-onset foveomacular vitelliform dystrophy (AOFVD), Best disease, autosomal recessive bestrophinopathy, age-related macular degeneration (AMD), and pachychoroid disease spectrum (PDS) disorders. Notably, increased subfoveal CT was associated with the presence and progression of subretinal hyperreflective material and subretinal fluid in AOFVD and Best disease. In PDS disorders, choroidal thickening, pachyvessels, and choroidal vascular hyperpermeability were identified as key contributors to RPE dysfunction and vitelliform lesion formation. Conversely, leptovitelliform maculopathy was characterised by thinner choroid in association with reticular pseudodrusen or subretinal drusenoid deposits. An important feature is CC dysfunction, which is often associated with pachyvessels, even in the absence of a clear pachychoroid-related phenotype or choroidal thickening. These findings underscore the importance of CT evaluation in clinical practice and highlight the need for further research to elucidate the complex relationship between CT and vitelliform maculopathies.},
}
@article {pmid41198978,
year = {2025},
author = {Gelisken, F and Koçak, N and Wenzel, CJ and Atay Dinçer, K and Wenzel, DA},
title = {Intravitreal anti-VEGF therapy for extrafoveal macular neovascularisation secondary to age-related macular degeneration: five-year results in a tertiary centre.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41198978},
issn = {1476-5454},
abstract = {OBJECTIVES: To assess the long-term efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy on best-corrected visual acuity (BCVA) and foveal morphology in patients with extrafoveal macular neovascularisation (MNV) secondary to age-related macular degeneration (AMD) over five years.<br><br>METHODS: A total of 104 eyes with treatment-na&#xef;ve extrafoveal MNV treated with intravitreal anti-VEGF injections were analysed retrospectively. BCVA was assessed at baseline and annually for five years. Central foveal thickness (CFT), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED), subretinal hyperreflective material (SHRM), and foveal atrophy (incomplete/complete retinal pigment epithelium and outer retinal atrophy (iRORA/cRORA))-were documented.<br><br>RESULTS: After five years, 46% of the eyes had unchanged or improved vision by one or more lines, whereas mean BVCA declined from 0.28&#x2009;&#xb1;&#x2009;0.20 logMAR at baseline to 0.50&#x2009;&#xb1;&#x2009;0.49 logMAR after five years (p&#x2009;=&#x2009;0.016). CFT, and the prevalence of IRF and SRF decreased significantly (p&#x2009;<&#x2009;0.001), while iRORA (p&#x2009;=&#x2009;0.041), and cRORA (p&#x2009;<&#x2009;0.001) increased by year five. Presence of cRORA was associated with worse five-year BCVA (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Anti-VEGF therapy for extrafoveal MNV secondary to AMD stabilised or improved BCVA in approximately half of the patients; however, mean BCVA declined after five years. Long-term functional benefits were limited due to morphological changes in the macula, such as subfoveal atrophy.},
}
@article {pmid41198612,
year = {2025},
author = {Ortega, AJ and Daniel, S and Renwick, M and Kambhampati, P and Thompson, KN and Collier, GE and Baker, EL and Zaki, H and Hulleman, JD},
title = {Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.},
journal = {Cell death &amp; disease},
volume = {16},
number = {1},
pages = {803},
pmid = {41198612},
issn = {2041-4889},
support = {R01 EY027785/EY/NEI NIH HHS/United States ; R01-DK128031//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; R01-EY027785//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; N/A//Edward N. and Della L. Thome Memorial Foundation (Thome Memorial Foundation)/ ; R01 DK128031/DK/NIDDK NIH HHS/United States ; R01 DK125352/DK/NIDDK NIH HHS/United States ; R01-DK125352//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; },
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism/deficiency ; Mice ; Caspase 1/metabolism/genetics ; *Macular Degeneration/genetics/pathology/metabolism ; *Extracellular Matrix Proteins/genetics/metabolism ; *Aging/pathology/genetics ; Inflammasomes/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; },
abstract = {Chronic, unresolved inflammation has long been speculated to serve as an initiating and propagating factor in numerous neurodegenerative diseases, including a leading cause of irreversible blindness in the elderly, age-related macular degeneration (AMD). Intracellular multiprotein complexes called inflammasomes in combination with activated caspases facilitate production of pro-inflammatory cytokines such as interleukin 1 beta. Specifically, the nucleotide-binding oligomerization (NOD)-like receptor protein 3 (NLRP3) has received heightened attention due to the wide range of stimuli to which it can respond and its potential involvement in AMD. In this study, we directly tested the role of Nlrp3 and its downstream effector, caspase 1 (Casp1) in mediating early AMD-like pathology (i.e., basal laminar deposits [BLamDs]) in wild-type (WT) mice and the Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) mouse model (p.R345W mutation in Efemp1). Compared to aged-matched controls, R345W[+/+] knockin mice demonstrated increased Muller cell gliosis, subretinal Iba-1[+] cells, higher Nlrp3 immunoreactivity in the retina, as well as significant transcriptional upregulation of complement component 3, Nlrp3, pro-Il1b, pro-caspase-1, and tissue inhibitor of matrix metalloproteinase 3 in the retinal pigmented epithelium (RPE)/choroid. These findings were accompanied by an age-related increase in BLamD formation in the R345W[+/+] mice. Genetic elimination of either Nlrp3 or Casp1 significantly reduced both the size and coverage of BLamDs in the R345W[+/+] background, highlighting an important and underappreciated pathway that could affect ML/DHRD onset and progression. Moreover, Nlrp3 knockout reduced spontaneous, age-related BLamDs in WT mice, suggesting translatability of our findings not only to rare inherited retinal dystrophies, but also potentially to AMD itself.},
}
@article {pmid41197713,
year = {2025},
author = {Allan, KC and Cohn, EF and Bala, S and Kim, SB and Kaelber, DC and Singh, RP and Talcott, KE and Mammo, DA and Rachitskaya, AV},
title = {Glucagon-Like Peptide-1 Receptor Agonist Use and Risk of Neovascular Age-Related Macular Degeneration in a National Cohort Study.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.10.020},
pmid = {41197713},
issn = {2468-6530},
abstract = {PURPOSE: To investigate the risk of neovascular age-related macular degeneration (AMD) in patients taking glucagon-like peptide-1 receptor agonists (GLP-1RAs).<br><br>DESIGN: A retrospective cohort study.<br><br>PARTICIPANTS: This study used the TriNetX network, a large aggregated electronic health records platform from health care organizations across the United States. Adults over the age of 60 years with &#x2265;1, 2, or 3 years of ophthalmology follow-up and medication prescription documentation were included.<br><br>METHODS: Patients were grouped into those taking GLP-1RAs, alternate glucose-lowering medications, and alternate lipid-lowering medications. Cohorts were propensity matched on demographics, chronic disease prevalence, and disease severity indicators.<br><br>MAIN OUTCOME MEASURES: The primary outcomes were risk of developing nonneovascular and neovascular AMD at 1, 2, and 3 years after initial medication prescription. A secondary analysis evaluated the risk of neovascular AMD in patients with nonneovascular AMD at baseline. Significance was defined as P < 0.05 and hazard ratio (HR) threshold >1.1 or <0.9 to minimize noise in large data sets.<br><br>RESULTS: Patients prescribed GLP-1RA had greater baseline chronic disease burden and worse disease severity metrics than comparator groups. Propensity matching effectively matched chronic disease prevalence at baseline. Glucagon-like peptide-1 receptor agonist prescription was associated with a significant reduction in risk of nonneovascular AMD compared with glucose-lowering medications over 1 (HR, 0.79; 95% confidence interval [CI], 0.66-0.94), 2 (HR, 0.75; 95% CI, 0.64-0.88), and 3 (HR, 0.77; 95% CI, 0.66-0.91) years. Similar protective effects were observed when compared with lipid-lowering medications after 2 (HR, 0.84; 95% CI, 0.71-0.99) and 3 (HR, 0.8; 95% CI, 0.68-0.94) years. There was a significant reduction in risk of neovascular AMD with GLP-1RA prescription across all time points compared with both alternate glucose-lowering and lipid-lowering medications. However, there was no significant impact of GLP-1RA on the risk of conversion from nonneovascular AMD at baseline to neovascular AMD.<br><br>CONCLUSIONS: These findings suggest that GLP-1RAs may provide protective effects against nonneovascular AMD and, importantly, did not show an increased risk of neovascular AMD. Future prospective trials are needed to validate these findings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41196411,
year = {2025},
author = {Furtado, J and Zapadka, TE and Park, H and Boyé, K and Demb, JB and Eichmann, A},
title = {Restoring compromised blood-retina-barrier integrity with Netrin-1 overexpression.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {82},
number = {1},
pages = {389},
pmid = {41196411},
issn = {1420-9071},
support = {R01 HL125811/HL/NHLBI NIH HHS/United States ; 834161/ERC_/European Research Council/International ; 1R01HLI125811//NHLBI Division of Intramural Research/ ; 830299//American Heart Association/ ; },
mesh = {*Netrin-1/genetics/metabolism ; Animals ; *Blood-Retinal Barrier/metabolism/pathology ; Mice ; Diabetic Retinopathy/pathology/metabolism/genetics ; Choroidal Neovascularization/pathology/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; Electroretinography ; Netrin Receptors/genetics ; Mice, Knockout ; Retina/metabolism/pathology ; },
abstract = {The blood-retina barrier (BRB) protects retinal neuronal function and enables vision. A compromised, leaky BRB is a hallmark of vision-threatening retinal diseases such as diabetic retinopathy (DR) and wet age-related macular degeneration (AMD) that affect millions of persons worldwide. Strategies to enhance BRB integrity hold promise as therapeutic interventions to prevent vision loss. Previous studies identified Netrin-1 (NTN1) as a key regulator of BRB stability and revealed reduced Netrin-1 signaling in DR patients, suggesting that Netrin-1 supplementation could help preserve BRB function and prevent disease progression. Herein, we used inducible genetic NTN1 overexpression to investigate effects on BRB development and maintenance. We show that global NTN1 overexpression converted leaky vessels at the P5 angiogenic front into a non-leaky state. In pathological settings, NTN1 overexpression reinforced BRB integrity in oxygen-induced retinopathy (OIR), improving electroretinogram (ERG) amplitudes and rescued vascular leak in laser-induced choroidal neovascularization (CNV). NTN1 overexpression or Ntn1 knockout minimally and transiently affected retinal angiogenesis. Global Unc5b deletion phenocopied vascular leak observed in Ntn1 deficient retinas, while angiogenesis defects differed between Ntn1 and Unc5b knockouts. These findings establish Netrin-1 as a promising therapeutic target for preventing BRB breakdown in retinal vascular diseases and suggest that reinforcing the Netrin-1/Unc5b signaling pathway may provide a strategy to selectively stabilize the BRB.},
}
@article {pmid41194821,
year = {2025},
author = {Almpanidou, S and Gounari, E and Goulas, A and Topouzis, F and Talimtzi, P and Kouzi-Koliakou, K and Karampatakis, V and Koliakos, G},
title = {Targeting Angiogenesis and Visual Cycle in Age-Related Macular Degeneration: The Role of Stem Cells and Vinpocetine.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e93878},
pmid = {41194821},
issn = {2168-8184},
abstract = {Purpose The purpose of this study was to evaluate whether bone marrow stem cells (BMSCs), vinpocetine, or their combination can attenuate amyloid-β (Aβ)-induced alterations in angiogenesis and visual cycle gene expression in a cellular model of age-related macular degeneration (AMD). Methods Human retinal pigment epithelium (RPE) cells (ARPE-19) were exposed to Aβ 1-42 for 24h and divided into four groups: (i) co-culture with BMSCs, (ii) treated with vinpocetine, (iii) treated with BMSCs and vinpocetine, and (iv) untreated control. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the mRNA expression levels of angiogenesis-related genes, vascular endothelial growth factor (VEGF-A) and pigment epithelium-derived factor (PEDF), and RPE-associated visual cycle genes: lecithin retinol acyltransferase (LRAT), retinoid isomerohydrolase (RPE65), retinol dehydrogenase 5 (RDH5), retinol dehydrogenase 10 (RDH10), and retinaldehyde-binding protein 1 (RLPB1). Results Aβ1-42 significantly reduced ARPE-19 cell viability (p=0.002); all treatments significantly restored viability. Aβ1-42 upregulated VEGF-A expression, which was significantly downregulated by all treatments. Although Aβ1-42 slightly increased PEDF expression, all treatments significantly enhanced its upregulation, with the combination therapy showing the greatest effect (p=0.006, 0.010, and 0.002, respectively). Furthermore, Aβ 1-42 induced upregulation of most visual cycle genes was reversed by all treatments. Conclusion Aβ1-42 induces cytotoxicity, angiogenesis, and dysregulation of visual cycle genes in RPE cells in vitro. BMSCs, vinpocetine, and their combination attenuate these effects, supporting a potential role in AMD therapy pending further investigation.},
}
@article {pmid41194565,
year = {2025},
author = {Singh, RB and Stettler, I and Romano, F and Parmar, UPS and Surico, PL and Ding, X and Kim, J and Rai, KK and Miller, JW and Miller, JB},
title = {Prevalence of Age-Related Macular Degeneration (AMD) in the United States: A Medicare-Based Analysis from 2014 to 2021.},
journal = {Ophthalmic research},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000548724},
pmid = {41194565},
issn = {1423-0259},
abstract = {PURPOSE: To assess the prevalence of age-related macular degeneration (AMD) among U.S. individuals aged 65 years and older.<br><br>DESIGN: Retrospective cohort study using data from the Vision and Eye Health Surveillance System (VEHSS), which included Medicare beneficiaries diagnosed with AMD between 2014 and 2021.<br><br>METHODS: The study analyzed Medicare-insured individuals aged 65 and older diagnosed with AMD during the study period. Crude prevalence rates were calculated for AMD and its stages-early, intermediate, wet AMD, and geographic atrophy (GA)-at national and state levels. Prevalence rates were compared by age, sex, and racial/ethnic groups. Statistical analyses included the Mann-Whitney U test for age and sex comparisons, the Brown-Forsythe one-way ANOVA for racial/ethnic comparisons, and the Dunnett T3 test for post-hoc analysis.<br><br>MAIN OUTCOME MEASURES: The primary outcomes were the prevalence and case counts of AMD and its stages across age, sex, and racial/ethnic groups.<br><br>RESULTS: In 2021, the VEHSS-Medicare database included 24,129,807 individuals aged 65 and older and the national AMD prevalence in this population was 10.40%. Prevalence rates for early AMD, intermediate AMD, wet AMD, and GA were 2.87%, 6.91%, 2.14%, and 0.73%, respectively. The estimated number of AMD cases increased from 2.33 million in 2014 to 2.51 million in 2021. AMD prevalence and its stages were significantly higher among individuals aged 85 and older compared to those aged 65-84, and among females compared to males. Post-hoc analyses showed significantly higher AMD prevalence in White individuals compared to all other racial groups.<br><br>CONCLUSIONS: AMD prevalence was 10.4% among individuals aged 65 and older, with higher rates observed in those aged 85 and older, females, and White individuals. These findings underscore the need for targeted public health strategies to address disparities in AMD care among older adults.},
}
@article {pmid41194409,
year = {2025},
author = {Zarei-Ghanavati, S and Shariati, MM and Hadi, Y and Khazaei, S and Yoo, SH},
title = {Cataract Surgery in the Context of Age-Related Macular Degeneration: Challenges and Considerations.},
journal = {Journal of cataract and refractive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.jcrs.0000000000001825},
pmid = {41194409},
issn = {1873-4502},
abstract = {Age-related macular degeneration (AMD) and cataracts commonly coexist in the aging population, posing unique diagnostic and therapeutic challenges for ophthalmologists. While cataract surgery can substantially improve visual function, outcomes are often influenced by the type and severity of underlying macular pathology. This narrative review explores current evidence on the impact of cataract surgery in AMD patients, including preoperative assessment strategies, intraoperative considerations, and postoperative visual expectations. The role of multimodal imaging in detecting subclinical macular changes, advanced intraocular lenses, and the debated relationship between cataract surgery and AMD progression are discussed. Emphasis is placed on personalized patient selection and counseling to optimize outcomes. Overall, with appropriate planning and patient-centered care, cataract surgery remains a safe and beneficial intervention for most individuals with AMD.},
}
@article {pmid41192738,
year = {2025},
author = {Aphale, P and Shekhar, H and Dokania, S},
title = {Comments on "Refining the translational pathway for senotherapeutics in age-related macular degeneration: Insights on biomarkers, delivery strategies, and clinical trial design".},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.10.002},
pmid = {41192738},
issn = {1879-3304},
}
@article {pmid41191669,
year = {2025},
author = {Zhou, J and He, Y and Wang, J and Cao, J and Huang, X and Chen, M and Ye, J},
title = {Malnutrition and age-related macular degeneration: mechanistic insights from UK Biobank metabolomic and imaging data.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {80},
number = {12},
pages = {},
doi = {10.1093/gerona/glaf229},
pmid = {41191669},
issn = {1758-535X},
support = {82330032//Key Program of the National Natural Science Foundation of China/ ; U20A20386//National Natural Science Foundation Regional Innovation and Development Joint Fund/ ; 2024C03204//Key Research and Development Program of Zhejiang Province/ ; 82301208//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Male ; *Macular Degeneration/epidemiology/etiology/metabolism/diagnostic imaging ; Female ; Middle Aged ; United Kingdom/epidemiology ; *Malnutrition/complications/metabolism/epidemiology ; Metabolomics ; Biological Specimen Banks ; Aged ; Risk Factors ; Cohort Studies ; Tomography, Optical Coherence ; UK Biobank ; },
abstract = {BACKGROUND: Malnutrition, characterized by degeneration of body composition due to reduced intake or inflammation, shares some common mechanisms with age-related macular degeneration (AMD), while their associations remain unexplored.<br><br>METHODS: This cohort study utilized data from the UK Biobank. Participants without pre-existing AMD and with complete malnutrition data were included. Cox regression was employed to evaluate the longitudinal association. An ElasticNet model was used to derive a metabolomic signature of malnutrition, which was subsequently assessed for association with AMD. Malnutrition and the metabolomic signature were further tested for associations with photoreceptor thinning. Structural equation modeling was applied to delineate underlying mechanisms.<br><br>RESULTS: A total of 444&#x2009;681 participants (mean age: 56.4&#x2009;&#xb1;&#x2009;8.1 years; 45.8% male) were included, with 32&#x2009;086 (7.2%) diagnosed with malnutrition at baseline. Over a median follow-up of 13.6 years, 10 009 AMD cases were identified. Malnutrition was associated with an increased risk of AMD (hazard ratio [HR]: 1.221, 95% CI, 1.144-1.304, p&#x2009;<&#x2009;.001). The metabolomic signature of malnutrition, derived from 127 metabolites, was significantly associated with AMD risk (per SD increase: HR: 1.073, 95% CI, 1.037-1.110, p&#x2009;<&#x2009;.001) and thinner photoreceptor layer (&#x3b2;&#x2009;=&#x2009;-.214, 95% CI, -0.314 to -0.114, p&#x2009;<&#x2009;.001). Structural equation modeling revealed that malnutrition increased AMD risk partially through metabolomic changes that induced photoreceptor thinning.<br><br>CONCLUSIONS: Malnutrition in middle-aged adults was significantly associated with increased risk of AMD, which was mediated by metabolomic alterations that impaired photoreceptor health.},
}
@article {pmid41191163,
year = {2025},
author = {Zhang, J and Kamoi, K and Zong, Y and Yang, M and Zou, Y and Ohno-Matsui, K},
title = {Inflammation and Immune Pathways in Myopia: An Overview on Pathomechanisms and Treatment Prospects.},
journal = {Clinical reviews in allergy &amp; immunology},
volume = {68},
number = {1},
pages = {98},
pmid = {41191163},
issn = {1559-0267},
support = {JPMJSP2180//JST SPRING/ ; 25K02864//Japan Society for the Promotion of Science/ ; 22FC0201//Ministry of Health, Labour and Welfare/ ; 23fk0108671h0001, 23fk0108672h000//Japan Agency for Medical Research and Development/ ; FY2023//Takeda Science Foundation/ ; },
mesh = {Humans ; *Myopia/therapy/immunology/etiology/metabolism/epidemiology ; *Inflammation/immunology/metabolism ; Animals ; Cytokines/metabolism ; Anti-Inflammatory Agents/therapeutic use ; Signal Transduction ; Inflammation Mediators/metabolism ; Disease Susceptibility ; Extracellular Matrix/metabolism ; Disease Management ; },
abstract = {Myopia represents a growing global public health challenge, characterized by increasing prevalence and associated complications such as myopic macular degeneration and retinal detachment. Although genetic and environmental factors are well-recognized contributors, emerging evidence supports a pathological link between inflammation and myopia progression. Epidemiological studies indicate a higher incidence of myopia among individuals with systemic or ocular inflammatory conditions. Inflammation perturbs the ocular immune microenvironment by upregulating pro-inflammatory cytokines and matrix metalloproteinase-2, thereby accelerating extracellular matrix (ECM) degradation and scleral remodeling, which culminates in axial elongation. Conversely, excessive axial elongation in high myopia triggers choroidal microvascular dysfunction, tissue hypoxia, and disruption of the blood-retinal barrier, leading to elevated inflammatory cytokines in the aqueous humor and vitreous, thereby raising the possibility of a self-perpetuating loop. Anti-inflammatory agents, including diacerein, resveratrol, and lactoferrin, have demonstrated therapeutic potential in experimental models by modulating inflammatory pathways, reducing pro-inflammatory cytokines, and preserving ECM integrity. However, their clinical efficacy and long-term safety require further validation. Elucidating the complex interplay between inflammation and myopia is pivotal for the development of targeted interventions, moving the focus of myopia management beyond optical correction towards disease-modifying strategies.},
}
@article {pmid41191064,
year = {2025},
author = {Hasan, N and Sadeghi, E and Gandhi, P and Vupparaboina, SC and Du, K and Eller, AW and Sahel, JA and Bollepalli, SC and Vupparaboina, KK and Chhablani, J},
title = {Demography, clinical profile and risk of retinal vein occlusion among patients with age-related macular degeneration - a tertiary hospital based study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41191064},
issn = {1435-702X},
abstract = {PURPOSE: Age-related macular degeneration (AMD) and retinal vein occlusion (RVO) share common risk factors and the risk of blindness is higher when both diseases coexist. This study aims to evaluate the risk factors of developing RVO among AMD patients and describe their clinical characteristics.<br><br>METHODS: In this single-center cohort study, 5618 Patients with AMD were divided into two groups: those who developed RVO and those who did not. Demographic, clinical and comorbidity profile were compared and multivariable logistic regression was performed to identify risk factors for RVO among patients with AMD. Additionally, baseline characteristics were compared between patients who developed central and branch retinal vein occlusion (CRVO and BRVO).<br><br>RESULTS: Among 5,618 patients with AMD, 55 developed RVO while 5563 did not. The prevalence of RVO among AMD patients was 9.79/1,000 AMD patients (95% CI:7.2-12.4) with an incidence rate of 2.04/1,000 person-years. Multivariate regression analysis revealed patients with lower BMI(OR:0.89,95%CI:0.84-0.95,p&#x2009;=&#x2009;<&#x2009;0.001), higher Charlson comorbidity index(OR:1.12,95%CI:1.02-1.22,p&#x2009;=&#x2009;0.019), African-American ethnicity(OR:4.07,95%CI:1.55-10.73,p&#x2009;=&#x2009;0.004), glaucoma(OR:2.09,95%CI:1.2-3.64,p&#x2009;=&#x2009;0.009) and neovascular AMD(OR:1.92,95%CI:1.07-3.43,p&#x2009;=&#x2009;0.028) have higher risk. On subgroup analysis, 27 patients developed CRVO, while 29 developed BRVO. The mean time to RVO development after the first visit for AMD was 4.42&#xb1;3.6 years. Patients with CRVO had significantly worse visual acuity(p&#x2009;<&#x2009;0.001), higher IOP(p&#x2009;=&#x2009;0.012), and a higher incidence of glaucoma(p&#x2009;=&#x2009;0.006) at baseline.<br><br>CONCLUSION: AMD Patients with lower BMI, higher CCI, African Americans, glaucoma, and neovascular AMD are at a higher risk of developing RVO. Identifying these risk factors is crucial to diagnose RVO promptly in patients with AMD as it has a higher prevalence compared to the general population, with a greater risk for vision loss.},
}
@article {pmid41189793,
year = {2025},
author = {Muşat, AAM and Zamfiroiu-Avidis, N and Ştefan, C and Andreea, S and Muşat, G and Udrea, G and Popescu, IS and Muşat, O},
title = {A Case Series of Serious Adverse Events Following Anti-VEGF Intravitreal Injections.},
journal = {Romanian journal of ophthalmology},
volume = {69},
number = {3},
pages = {450-454},
pmid = {41189793},
issn = {2501-2533},
mesh = {Humans ; Intravitreal Injections/adverse effects ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Retrospective Studies ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Endophthalmitis/chemically induced/diagnosis ; *Visual Acuity ; Male ; Female ; Aged ; *Ranibizumab/adverse effects/administration &amp; dosage ; Middle Aged ; *Bevacizumab/adverse effects/administration &amp; dosage ; *Retinal Detachment/chemically induced/diagnosis ; *Cataract/chemically induced/diagnosis ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To highlight serious adverse effects regarding intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, which is widely used for the treatment of retinal diseases, including two cases of post-injection endophthalmitis, one of which was complicated by rhegmatogenous retinal detachment, and one case of secondary cataract following a potentially unnecessary injection.<br><br>METHODS: A retrospective analysis of three cases that developed complications after intravitreal anti-VEGF therapy.<br><br>RESULTS: All cases resulted in a decline in best corrected visual acuity (BCVA) that required additional surgical procedures.<br><br>DISCUSSION: While intravitreal anti-VEGF therapy has become the standard in the treatment of various retinal pathologies, it is not without risks. This case series presents significant adverse outcomes, emphasizing the potential for severe anatomical and functional consequences. As the global volume of anti-VEGF intravitreal injections increases, so must our commitment to patient safety, precision in diagnosis, and ethical decision making.<br><br>CONCLUSION: Although generally safe and commonly used in clinical practice, physicians must be aware of the risks of anti-VEGF therapy and must remain vigilant regarding patient selection and risk-benefit considerations.},
}
@article {pmid41189788,
year = {2025},
author = {Stoica, AM and Jurja, S and Dervis, N},
title = {The Role of Vitamin D in Retinal Physiology.},
journal = {Romanian journal of ophthalmology},
volume = {69},
number = {3},
pages = {315-321},
pmid = {41189788},
issn = {2501-2533},
mesh = {Humans ; *Vitamin D/physiology ; *Retina/physiology ; *Retinal Diseases/physiopathology/metabolism/prevention &amp; control ; Oxidative Stress/physiology ; Vitamin D Deficiency/physiopathology ; Animals ; },
abstract = {Vitamin D plays a crucial role in ocular health, particularly in the function and protection of the retina. This fat-soluble vitamin is synthesized in the skin in response to UVB radiation and can also be obtained from dietary sources. Research indicates that vitamin D has neuroprotective properties, which are essential for retinal cell survival and function. The active form of vitamin D, calcitriol, has been shown to modulate inflammation and oxidative stress in retinal tissues, thus potentially preventing retinal degeneration diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Furthermore, vitamin D receptors are expressed in various retinal cells, suggesting that vitamin D directly influences retinal physiology. Deficiency in vitamin D has been associated with an increased risk of chronic eye diseases, emphasizing the importance of maintaining adequate vitamin D levels for preserving retinal health. Ongoing studies are needed to elucidate further the molecular mechanisms underlying the protective effects of vitamin D on the retina and to explore its therapeutic potential in retinal disorders.},
}
@article {pmid41189785,
year = {2025},
author = {Stoica, AM and Jurja, S and Dervis, N},
title = {Anti-VEGF therapy - a new hope in AMD treatment.},
journal = {Romanian journal of ophthalmology},
volume = {69},
number = {3},
pages = {322-327},
pmid = {41189785},
issn = {2501-2533},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Choroidal Neovascularization/drug therapy/etiology ; *Macular Degeneration/drug therapy/complications ; Ranibizumab ; *Wet Macular Degeneration/drug therapy ; Bevacizumab ; },
abstract = {Choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) represents a significant global cause of visual impairment. Contemporary therapeutic approaches for neovascular AMD focus on inducing regression of CNV by inhibiting critical growth factors involved in angiogenesis. For nearly two decades, vascular endothelial growth factor (VEGF) has been the principal therapeutic target, with multiple intravitreally administered agents developed to achieve anatomical restoration and improved visual outcomes through sustained dosing.},
}
@article {pmid41189775,
year = {2025},
author = {Guzun, OV and Zadorozhnyy, OS and Konovalova, NV and Bezdetko, PA and Korol, AR and Dumbrăveanu, LG and Cușnir, VN and Cușnir, VV},
title = {Reducing the risk of age-related macular degeneration progression - five-year follow-up study in Ukraine and Moldova.},
journal = {Romanian journal of ophthalmology},
volume = {69},
number = {3},
pages = {340-349},
pmid = {41189775},
issn = {2501-2533},
mesh = {Humans ; Ukraine/epidemiology ; Disease Progression ; Follow-Up Studies ; Male ; Female ; Prospective Studies ; Aged ; *Dietary Supplements ; *Macular Degeneration/epidemiology/prevention &amp; control/diagnosis ; Moldova/epidemiology ; *Antioxidants/administration &amp; dosage/therapeutic use ; Time Factors ; *Visual Acuity ; Risk Factors ; Middle Aged ; Vitamins ; *Fatty Acids, Omega-3/administration &amp; dosage ; },
abstract = {This open prospective study aimed to evaluate the dynamics of progression of early and intermediate age-related macular degeneration (AMD) against the background of continuous use of the nutraceutical formula AREDS2, which includes omega-3 polyunsaturated fatty acids (PUFAs), vitamin D, resveratrol, and photobiomodulation (PBM), over a 5-year follow-up in patients from Ukraine and Moldova. Examining 126,400 patients, 163 patients (304 eyes) with early and intermediate stages of AMD were treated (5-year follow-up). Patients were divided into two groups. Patients in the 1st group (149 eyes) were prescribed a nutraceutical formula based on AREDS2 with omega-3 PUFAs, vitamin D, and resveratrol (Nutrof®Forte 1 capsule once a day continuously). The second group (155 eyes) included patients who irregularly took various vitamin-antioxidant complexes. All patients underwent PBM every 6 months. The five-year prevalence of early and intermediate AMD was estimated using data from leading ophthalmological centers in Ukraine (Odesa - 7.1%, Kharkiv - 6.6%) and Moldova (6.3%). AMD progression in the multivariate Cox regression model over five years showed a 3.24-fold reduction in relative risk (95% CI: 2.15-4.79, p=0.000) for patients with early and intermediate AMD who regularly took the recommended nutraceutical (compared to those who irregularly took various vitamin-antioxidant complexes). Patients with early and intermediate AMD are recommended to undergo courses of PBM every six months. Additionally, it is crucial to address cardiovascular issues and consistently use the AREDS2 nutraceutical formula. Adherence to these recommendations can reduce the likelihood of disease progression by at least 3.24 times over the next 5 years.},
}
@article {pmid41189030,
year = {2025},
author = {Arnal, L and Mesfin, Y and Xu, C and Salvi, A and Mishra, K and Ludwig, CA},
title = {Beyond refractive error: myopia's exponential burden on retinal health with each diopter.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {121},
pmid = {41189030},
issn = {2056-9920},
support = {K23 EY035741/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; NEI P30-EY026877//P30 Vision Research Core Grant/ ; K23EY035741//National Eye Institute K23 Grant/ ; },
abstract = {BACKGROUND: As myopia reaches epidemic levels worldwide, its role in driving vision-threatening retinal complications is increasingly urgent. This study quantifies the burden of myopia by examining its association with key retinal diseases and how risk escalates with increasing severity.<br><br>METHODS: We conducted a retrospective cohort study using the STARR clinical data warehouse, including all patients with &#x2265;&#x2009;1 documented eye visit. Myopia severity was defined by spherical equivalent and axial length, classifying patients as non-myopic, myopic, highly myopic, or severely myopic. Primary outcomes included six retinal diseases associated with myopia: choroidal neovascularization (CNV), myopic macular degeneration (MMD), foveoschisis, macular hole (MH), rhegmatogenous retinal detachment (RRD), and foveal retinal detachment (FRD). Adjusted logistic regression estimated odds by myopia severity and spherical equivalent. Mean age at diagnosis was compared across groups.<br><br>RESULTS: Retinal complications occurred at younger ages with increasing myopia severity. Compared to non-myopes, myopic, highly myopic, and severely myopic patients had 2.45 (95% CI: 2.36-2.55), 2.46 (95% CI: 2.31-2.62), and 8.15 (95% CI: 7.17-9.27) times higher odds, respectively, of developing any retinal complication. Per diopter increase in myopia, the odds of each complication increased: CNV (OR 1.11; 95% CI: 1.09-1.12), MMD (OR 1.22; 95% CI: 1.18-1.25), foveoschisis (OR 1.22; 95% CI: 1.16-1.28), MH (OR 1.06; 95% CI: 1.05-1.08), FRD (OR 1.23; 95% CI: 1.16-1.32), and RRD (OR 1.10; 95% CI: 1.10-1.11). In severe myopes, odds were markedly elevated: CNV (OR 22.90), MMD (OR 60.19), foveoschisis (OR 102.98), MH (OR 6.69), FRD (OR 22.72), and RRD (OR 6.84).<br><br>CONCLUSIONS: Myopia is independently associated with higher odds of retinal diseases, and this risk increases incrementally with severity. These findings support a dose-response relationship and highlight the importance of early risk stratification, tailored monitoring, and timely referral in patients with high and severe myopia.},
}
@article {pmid41188571,
year = {2025},
author = {Eilon, E and Lishinsky-Fischer, N and Levy, J},
title = {Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41188571},
issn = {1476-5454},
abstract = {BACKGROUND/OBJECTIVES: To assess whether systemic prostacyclin analogue (PCA) therapy in patients with pulmonary arterial hypertension (PAH) is associated with a reduced long-term risk of developing age-related macular degeneration (AMD).<br><br>SUBJECTS/METHODS: A retrospective cohort study was conducted using the TriNetX global health research network. Patients aged &#x2265;50 with a diagnosis of PAH were included and stratified by PCA treatment. Propensity score matching (1:1) was applied to balance demographics and comorbidities. Incident diagnoses of non-neovascular AMD (non-nvAMD) and neovascular AMD (nvAMD) were compared across six follow-up intervals (3-15 years) using Kaplan-Meier analysis and Cox proportional hazards models.<br><br>RESULTS: Following matching, 9862 PCA-treated and 9862 untreated PAH patients were analysed. PCA-treated patients showed a consistently lower risk of non-nvAMD across all follow-up periods (hazard ratios [HRs] 0.30-0.37; all p&#x2009;<&#x2009;0.001). A similar protective trend was observed for nvAMD, with significant associations emerging at longer follow-up (HR&#x2009;=&#x2009;0.37-0.39 at 10-15 years; p&#x2009;<&#x2009;0.05). The protective effect was robust and durable over time.<br><br>CONCLUSIONS: Systemic administration of prostacyclin analogues is associated with a significant and sustained reduction in AMD risk among patients with PAH. These findings suggest a potential preventive role for PCAs in AMD pathogenesis and merit further investigation in broader populations.},
}
@article {pmid41187450,
year = {2025},
author = {Dashti, R and Safaei, F and Sadeghian, G and Hosseini, SA and Salimibani, M},
title = {Peptide-functionalized nanomaterials for controlled drug delivery and regenerative therapies in retinal diseases.},
journal = {Journal of biomaterials applications},
volume = {},
number = {},
pages = {8853282251395196},
doi = {10.1177/08853282251395196},
pmid = {41187450},
issn = {1530-8022},
abstract = {Degenerative retinal diseases, such as diabetic retinopathy, age-related macular degeneration (AMD), and retinitis pigmentosa, cause irreversible vision loss by destroying vital retinal cells and represent major global health concerns. Traditional therapies have limited success in fully restoring vision due to the complex retinal structure and blood-retinal barriers (BRBs), though they may help alleviate symptoms or slow disease progression in some cases. Nanochemistry and peptide-based systems represent breakthrough approaches by leveraging nanoscale precision and biological specificity. This review examines the chemical design and synthesis of nanoparticles (NPs), nanoscaffolds, and peptide conjugates used in retinal neural regeneration. It also explores their biomedical applications, especially in targeted drug delivery, tissue engineering, and cellular repair. Biodegradable polymeric NPs, liposomes, and hybrid nanostructures are designed to cross barriers, release drugs in a controlled manner, and enhance biocompatibility. PEGylation improves stability and reduces immune responses in the ocular environment, while peptide functionalization enables specific cellular targeting and minimizes inflammatory reactions. Peptide-functionalized platforms, such as RGD-modified NPs and self-assembling hydrogels, provide receptor-mediated targeting and extracellular matrix (ECM) mimicry to support retinal regeneration for improved stem cell differentiation and neuroprotection. We discuss drug/gene delivery mechanisms, cellular interactions, and immune modulation, as well as neuroprotection, stem cell therapy, and diagnostic applications. Preclinical studies have demonstrated promising efficacy in animal models; however, concerns regarding scalability, long-term safety, and non-invasive delivery persist. Next-generation technologies, such as stimuli-responsive NPs, computationally designed peptides, and patient-specific delivery systems, are on the horizon to address unmet clinical needs. By marrying nanochemistry's precision with peptides' bioactivity, these technologies have the potential to transform retinal disease treatment, enabling the restoration of vision and an improvement in quality of life for millions of people worldwide.},
}
@article {pmid41187156,
year = {2025},
author = {Li, Y and Wang, B and Luo, X and Zhang, M and Hu, Q and Li, X},
title = {Machine learning models for risk prediction of age-related macular degeneration in Fujian eye study.},
journal = {PloS one},
volume = {20},
number = {11},
pages = {e0335620},
pmid = {41187156},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/epidemiology/diagnosis ; *Machine Learning ; Female ; Male ; Aged ; Cross-Sectional Studies ; Risk Factors ; Logistic Models ; Middle Aged ; Aged, 80 and over ; Support Vector Machine ; },
abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a retinal disorder that significantly impairs vision. This study investigates various machine learning models for predicting AMD risk, laying the groundwork for further research using big data and determining the most effective predictive model.<br><br>METHODS: Utilizing data from 8211 records with 39 features from the Fujian Eye Study, a cross-sectional epidemiological investigation, several machine learning models were developed and assessed. The models included logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Data preprocessing, feature selection, and model training were all key components of the study.<br><br>RESULTS: After evaluating multiple models, the logistic regression model emerged as the most accurate, achieving a balanced accuracy of 0.6364. Among the predictive features, educational background had the highest influence on the model's predictions, with an average SHAP (SHapley Additive exPlanations) value of 0.8199. Other significant factors included outdoor time and left eye spherical equivalent (OSSE), with SHAP values of 0.6474 and 0.6377, respectively.<br><br>CONCLUSION: This study confirms that logistic regression is the most effective machine learning model for predicting AMD risk, with educational background identified as the most critical risk factor.},
}
@article {pmid41186544,
year = {2025},
author = {Lou, J and Liao, X},
title = {Re: Friedman et al: Randomized Trial of Biosimilar ABP 938 Compared with Reference Aflibercept in Adults with Neovascular Age-Related Macular Degeneration (2025 Aug 5:S2468-6530(25)00351-3. doi: 10.1016/j.oret.2025.07.015. Online ahead of print.).},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.10.003},
pmid = {41186544},
issn = {2468-6530},
}
@article {pmid41184811,
year = {2025},
author = {Wang, Y and Wei, W and Pei, X and Zhan, H and Tang, Y and Li, Y and Bai, J and Li, J},
title = {PDC-DETR: a Parallel Dilated Convolutional Detection Transformer for preliminary screening of multiple macular degeneration.},
journal = {BMC medical imaging},
volume = {25},
number = {1},
pages = {439},
pmid = {41184811},
issn = {1471-2342},
support = {2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; 2023ZXYG07//Dalian Science and Technology Bureau,China&#xff0c;/ ; },
abstract = {Current diagnostic approaches for macular degeneration in optical coherence tomography (OCT) images often lead to misdiagnosis due to their limited ability to capture the disease’s multiscale and irregular features. We present PDC-DETR, a Parallel Dilated Convolutional Detection Transformer, which introduces three major innovations for accurate and efficient macular degeneration analysis. First, a Parallel Feature-Optimized Attention Pyramid Network (PFOAPN) enables simultaneous modeling of global context and local details through multi-scale feature pathways. Second, a novel Wise-MPDIoU loss dynamically adjusts to variations in image quality while improving lesion localization accuracy. Third, the lightweight design ensures real-time clinical applicability, requiring only 38.2 MB parameters and 58.5 GFLOPs, while achieving 94.1% accuracy across five macular degeneration categories at 71 FPS. This study establishes a new benchmark for automated OCT-based retinal disease detection, providing both high diagnostic accuracy and practical clinical deployment potential.},
}
@article {pmid41183785,
year = {2025},
author = {Basilious, A and Yuan, AT and Sheidow, TG},
title = {Outcomes of 16-week extension of anti-VEGF therapy in neovascular age-related macular degeneration.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2025.10.002},
pmid = {41183785},
issn = {1715-3360},
abstract = {OBJECTIVE: To determine the outcomes of extending anti-VEGF injection intervals to 4 months in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: A prospective cohort study.<br><br>PARTICIPANTS: Patients undergoing injections with standard-dose anti-VEGF (aflibercept, ranibizumab) with documented disease stability at 3-month injection intervals for &#x2265;2 years.<br><br>METHODS: The injection interval was extended to 4 months. The primary outcome of disease stability was defined as no clinical evidence of lesion growth, blood, or intraretinal or new subretinal fluid seen on ocular coherence tomography (OCT). Demographic data, visual acuity, exam findings, and OCT data were collected.<br><br>RESULTS: This study included 88 eyes (83.4 &#xb1; 7.3 years, 64.8% female) with nAMD extended to injection intervals of 4 months (56 eyes with aflibercept and 32 with ranibizumab). The recurrence rate was 10.2% (9/88). Four eyes recurred after the first 4-month extension interval, 2 eyes at the 8-month follow-up, 2 eyes at 16 months, and 1 eye at 22 months. In eyes with a recurrence (n&#x202f;=&#x202f;9), there was no significant difference (p > .05) between mean visual acuity prior to recurrence (0.18 &#xb1; 0.13 [20/30]) and at final follow-up postrecurrence (0.21 &#xb1; 0.17 [20/30]). All but 1 case returned to within 1 Snellen line of visual acuity at final follow-up. All eyes were able to regain stability at 3- or 4-month injection intervals.<br><br>CONCLUSIONS: In nAMD patients with disease stability at 3-month injection intervals for at least 2 years, the majority remained stable when extended to 4 months. Recurrences were able to achieve stability again with shorter injection intervals, without a persistent decline in visual acuity.},
}
@article {pmid41183696,
year = {2026},
author = {Cheng, Y and Gu, S and Yu, H and Jin, J and Cheng, H and Zhang, H and Lin, J and Li, M and Zhu, H and Wang, T and Huang, Q and Liu, Y and Yue, P and Li, W and Ling, S},
title = {PYGM downregulates necroptosis signaling to attenuate sodium iodate-induced RPE cell degeneration.},
journal = {Cellular signalling},
volume = {137},
number = {},
pages = {112206},
doi = {10.1016/j.cellsig.2025.112206},
pmid = {41183696},
issn = {1873-3913},
mesh = {*Iodates/toxicity ; *Necroptosis/drug effects ; Animals ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; Mice ; *Macular Degeneration/metabolism/pathology/genetics/chemically induced ; Signal Transduction/drug effects ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Down-Regulation ; Mice, Inbred C57BL ; Disease Models, Animal ; Cell Line ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) causes incurable vision loss in elderly individuals, and there is currently only a rarely effective treatment for dry AMD. Necroptosis is attracting increasing attention in the context of AMD. This study aimed to elucidate the mechanisms underlying the induction of abnormal necroptosis in AMD.<br><br>METHODS: Sodium iodate (SI) was used to establish in vitro and in vivo retinal pigment epithelium cell (RPE) degeneration models and to simulate dry AMD-like conditions. Phenotypes and classic necroptosis markers were identified. RNA-seq was performed on the retinas of RPE-degeneration mice and combined with the GSE29801 microarray data of human AMD retinal samples to identify the key genes regulating necroptosis. Key genes were overexpressed both in vivo and in vitro to further validate their function in necroptosis and RPE degeneration.<br><br>RESULTS: Necroptosis phenotypes and the expression of the necroptosis markers RIPK1, RIPK3, and MLKL were upregulated in both SI-treated ARPE-19 cells and the RPE layer of mice. Transcriptome data from SI-treated mice and patients with AMD revealed that the reduced expression of PYGM is implicated in the regulation of necroptosis. PYGM overexpression in RPE cells and mouse retinas alleviated SI-induced RPE degeneration.<br><br>CONCLUSIONS: This study confirmed that PYGM attenuates necroptosis in cellular and animal models resembling dry AMD, providing a new perspective on exploring novel AMD treatment targets.},
}
@article {pmid41183353,
year = {2025},
author = {Sabbagh, F and Zargarian, SS and Kosik-Kozioł, A and Nakielski, P and Pierini, F},
title = {Hydrogel-based ocular drug delivery systems.},
journal = {Journal of materials chemistry. B},
volume = {13},
number = {46},
pages = {14982-15006},
doi = {10.1039/d5tb01575h},
pmid = {41183353},
issn = {2050-7518},
mesh = {*Hydrogels/chemistry ; Humans ; *Drug Delivery Systems ; Animals ; *Ophthalmic Solutions/chemistry ; },
abstract = {Ocular drug delivery is challenging due to physical and physiological barriers, such as the corneal epithelium and blood-retinal barrier, resulting in limited bioavailability (<5% for eye drops) and fast degradation. For the reason of improving drug delivery to the anterior and posterior ocular segments, this review attempts to assess hydrogel-based systems as versatile systems to overcome these barriers. We thoroughly explore physicochemical and performance characterization approaches (e.g., swelling, rheology, drug release kinetics), hydrogel fabrication methods (e.g., chemical crosslinking, 3D printing), and their uses in new and commercial products. Significant advances highlight the controlled release, mucoadhesion, and biocompatibility of hydrogels, which allow prolonged drug delivery as demonstrated by commercial products such as DEXTENZA® and ReSure® Sealant for corneal sealing and post-operative inflammation control. New technologies provide greater accuracy and less invasiveness. Examples include bioengineered hydrogels for retinal regeneration, systems integrated with nanotechnology, and stimuli-responsive hydrogels (such as pH-sensitive chitosan for glaucoma). By addressing mechanical stability and regulatory criteria, characterization techniques guarantee the suitability of the hydrogel for ocular applications. Hydrogels exhibit considerable promise for personal and least invasive treatments, despite challenges like scalability and high production costs. With implications for improving clinical outcomes and patient compliance through novel biomaterials, this review highlights the important role of hydrogels in ocular drug delivery and offers an outline for future advancements in the treatment of diseases like glaucoma, age-related macular degeneration, and dry eye syndrome.},
}
@article {pmid41183001,
year = {2025},
author = {Hu, X and Tang, Y and Zhang, H and Wang, Z and Sun, J},
title = {Alu RNA-transfected Primary Mouse Retinal Pigment Epithelium: A Pathologically Relevant In Vitro Model for Age-related Macular Degeneration.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {224},
pages = {},
doi = {10.3791/68570},
pmid = {41183001},
issn = {1940-087X},
mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/pathology/metabolism/cytology ; *Macular Degeneration/pathology/genetics ; *Disease Models, Animal ; *Alu Elements/genetics ; *Transfection/methods ; *RNA/genetics ; Mice, Inbred C57BL ; },
abstract = {Age-related macular degeneration (AMD), particularly non-exudative AMD, requires experimental models that better replicate human pathology. Current in vivo models remain technically demanding and time-intensive, whereas conventional in vitro systems fail to recapitulate disease-specific pathological triggers. Here, we present a method to establish a retinal pigment epithelial (RPE) degeneration model using primary mouse RPE cells transfected with Alu RNA, a retrotransposon directly implicated in geographic atrophy pathology. This protocol details the enzymatic isolation of primary mouse RPE cells, followed by Alu RNA transfection to induce RPE degeneration. Validation integrates morphological (hexagonal architecture), functional (polarity loss and mouse protein ZO-1 disruption), and molecular analysis (quantitative PCR). As a result, we observed multifactorial changes triggered by Alu RNA transfection: inflammatory cytokine secretion (mouse genes Ifn-β, Il-6, Tnf-α; p < 0.05) and cellular senescence (mouse genes p21 and p53 upregulation; p < 0.05). Compared to traditional acute stress models, this system recapitulates chronic inflammatory-degenerative cascades of AMD through standardized techniques, ensuring reproducibility. By combining aspects of simplified in vitro assays and complex in vivo models, this approach could serve as a preliminary platform for exploring retrotransposon-driven mechanisms and screening potential therapeutic candidates.},
}
@article {pmid41182913,
year = {2025},
author = {Akçay, G and Kutlutürk Karagöz, I and Doğan Gökçe, G},
title = {Evaluating anxiety and depression levels in patients undergoing intravitreal injections and investigation of contributing factors.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251392036},
doi = {10.1177/11206721251392036},
pmid = {41182913},
issn = {1724-6016},
abstract = {PurposeTo evaluate anxiety and depression levels in patients receiving intravitreal injections for diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO), and their associations with visual acuity, disease type, and demographic factors.MethodsThe study included 90 patients (43 males and 47 females) mean age 73.9 ± 12.4 years; (range: 22-92 years). Anxiety levels were assessed using the state anxiety form of the State-Trait Anxiety Inventory (STAI-S), and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Best-corrected visual acuity (BCVA) was recorded, and patients were evaluated according to disease type, severity of visual impairment, and number of injections.ResultsThe mean STAI-S score was 36.2 ± 8.9, and that of HADS was 13.9 ± 12.6. There were no significant differences in STAI-S scores between the disease groups (p = 0.17). However, HADS scores were significantly lower in the RVO group than in the DME and AMD groups (p = 0.02, p = 0.04). A significant association was observed between severity of visual impairment and STAI-S scores (p = 0.016), with moderate visual impairment showing higher anxiety levels than mild and severe impairment (p = 0.07, p = 0.02). However, HADS scores were not significantly associated with visual acuity (p = 0.058). Women exhibited higher HADS scores (p = 0.036). Neither injection frequency nor waiting time significantly affected STAI-S or HADS scores (p > 0.05).ConclusionPatients receiving intravitreal injections have varying levels of anxiety and depression, considering disease type, sex, and severity of visual impairment affecting these psychological parameters. These findings provide invaluable insights into the importance of psychological support in ophthalmic care.},
}
@article {pmid41182446,
year = {2025},
author = {Entezari, Z and Mahootchi, M and Eskandari, M and Ahmadieh, H},
title = {Artificial intelligence-driven diagnosis for age-related macular degeneration bridging pathology and engineering: a survey.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {456},
pmid = {41182446},
issn = {1573-2630},
mesh = {Humans ; *Macular Degeneration/diagnosis ; *Artificial Intelligence ; Tomography, Optical Coherence/methods ; Disease Progression ; Early Diagnosis ; Risk Factors ; },
abstract = {Age-related macular degeneration (AMD) is the primary reason for severe visual impairments, making early diagnosis critically important. This paper provides a comprehensive review of the methods used to support screening and diagnostic decisions, focusing on four categories: early, intermediate, and advanced stages of AMD, in addition to AMD across all stages. In this regard, a reference framework is initially proposed to describe research perspectives in pathology. Utilizing this framework, a literature review is conducted to identify the most reliable demographic, environmental, and comorbidity-related risk factors, clinical symptoms, and various aspects of AMD pathology, setting the necessary prerequisites for subsequent sections. The potential application of risk factors is also explained for personalized medicine. While phenotypic risk factors and genetic variants play a crucial role in predicting the progression of AMD, it is more vital to examine demographic and environmental factors at earlier stages for developing effective prevention plans. Therefore, the selection of appropriate risk factors emerges as a critical area of research. Afterward, we present a comparative analysis of different screening and diagnostic methods pertinent to AMD from an industrial engineering perspective. This analysis brings attention to the suite of artificial intelligence (AI) to describe, analyze, and evaluate diagnostic models, thereby providing a reference outline for clinical practice. AI methods can automate the interpretation of retinal images, serving as a supportive tool for clinical decision-making to improve the management of disease progression. In general, this survey highlights the necessity of developing more integrated methods to support decisions at different planning levels.},
}
@article {pmid41182355,
year = {2025},
author = {Shmueli, O and Batash, T and Nitzan, I and Chowers, I and Tiosano, L},
title = {Cataract surgery in eyes with adult-onset foveomacular-vitelliform dystrophy.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41182355},
issn = {1435-702X},
abstract = {PURPOSE: To assess the outcomes and safety of cataract surgery in Adult-Onset Foveomacular-Vitelliform dystrophy (AFVD) patients.<br><br>METHODS: This retrospective study analyzed eyes with AFVD that underwent cataract surgery in a tertiary center, comparing them with eyes affected by none and neovascular age-related macular degeneration (NVAMD). Data included demographics, best-corrected visual acuity LogMAR (VA), eye examination results, and optical coherence tomography (OCT) results. The primary outcome was improvement in VA. A secondary outcome was AFVD progression such as the development of choroidal neovascularization (CNV) or retinal atrophy.<br><br>RESULTS: The cohort included 83 eyes (18 with AFVD, 27 with none-NV AMD, and 38 with NVAMD). AFVD eyes showed significant improvement in VA&#xb1;SD from pre-surgery (0.60&#x2009;&#xb1;&#x2009;0.34) to 1 month (0.23&#x2009;&#xb1;&#x2009;0.11; P&#x2009;<&#x2009;0.0001) and 12 months post-operatively (0.26&#x2009;&#xb1;&#x2009;0.12; P&#x2009;<&#x2009;0.0001). No cases of CNV or major AFVD progression changes were observed over 12 months of follow up. However, at last follow-up (62.20&#x2009;&#xb1;&#x2009;39.30 months) there was increased proportion of atrophic AFVD (44.40% compared to 5.50% at baseline; P&#x2009;=&#x2009;0.10). No difference was found comparing VA improvement one month after surgery of none-NV AMD, NVAMD and AFVD (AFVD&#x2009;=&#x2009;0.37&#x2009;&#xb1;&#x2009;0.36, none-NV AMD&#x2009;=&#x2009;0.47&#x2009;&#xb1;&#x2009;0.68, NVAMD&#x2009;=&#x2009;0.28&#x2009;&#xb1;&#x2009;0.37; P&#x2009;=&#x2009;0.29). In the none-NV AMD group, one eye developed CNV ten months post-operatively and another eye demonstrated worsening retinal atrophy one-month post-surgery. In the NVAMD group, 9 eyes developed retinal atrophy at last follow up.<br><br>CONCLUSION: Cataract surgery in&#xa0;AFVD eyes led to significant visual acuity improvement and demonstrated good safety with no&#xa0;new CNV or retinal atrophy. The similar visual improvement across the AFVD, none-NV AMD&#xa0;and NVAMD groups suggests the procedure's efficacy and safety for AFVD patients.},
}
@article {pmid41181732,
year = {2025},
author = {Tamai, R and Nizawa, T and Kawamata, Y and Iwase, T and Baba, T},
title = {Switching From Aflibercept 2 mg to 8 mg in Vitrectomized Eyes With Neovascular Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e93645},
pmid = {41181732},
issn = {2168-8184},
abstract = {Vitrectomy may alter intravitreal pharmacokinetics through the removal of the vitreous gel, potentially accelerating the clearance of anti-vascular endothelial growth factor (VEGF) agents. Clinical trials and most real-world studies on neovascular age-related macular degeneration (nAMD) generally exclude vitrectomized eyes, and the efficacy of anti-VEGF therapy in this subgroup remains unclear. Aflibercept 8 mg, approved in Japan in 2024, delivers four times the dose of the conventional 2 mg formulation and is designed to improve durability and extend treatment intervals. We report three vitrectomized eyes from three patients with nAMD who exhibited persistent or recurrent exudation despite short-interval (≤8 weeks) aflibercept 2 mg therapy under a treat-and-extend regimen. Switching to aflibercept 8 mg led to the resolution of fluid in all cases and enabled interval extension. No ocular or systemic adverse events were observed. These findings suggest that aflibercept 8 mg can achieve improved anatomical outcomes and greater treatment durability in vitrectomized eyes with nAMD, thereby potentially reducing the treatment burden in this challenging subgroup. Larger prospective studies are required to validate these findings.},
}
@article {pmid41181297,
year = {2025},
author = {Agius, D and Mamo, JJ and Calleja, N and Cassar, D and Marku, X and Nappa, MC and Zammit, M and Pace, ME and Carbonaro, F},
title = {Markedly Lower Rates of Age-Related Macular Degeneration in Malta Compared to European Countries: Results from The Malta Eye Study, Indicating Possible Divergent Genetic Ancestry?.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3961-3971},
pmid = {41181297},
issn = {1177-5467},
abstract = {PURPOSE: To estimate the prevalence of age-related macular degeneration (ARMD) in a nationally representative sample of older adults from Malta, evaluate associations with established risk factors, and compare rates with those reported in other European populations, where substantial variation has been observed.<br><br>PATIENTS AND METHODS: A population-based cross-sectional study was conducted involving 1794 participants aged 50-80 years from Malta (1% of the represented population), recruited as part of The Malta Eye Study. Standardized ophthalmic examinations were performed, including retinal imaging graded for ARMD according to Age-Related Eye Disease Study criteria and optical coherence tomography scans. Data on demographics, medical history, behavioural risk factors, and ocular characteristics were collected via structured questionnaires. Associations were assessed using multivariable logistic regression. DNA samples were also collected for future genetic analyses.<br><br>RESULTS: The overall prevalence of ARMD was 6.5% (95% CI 5.4-7.8%), with early ARMD accounting for 5.6% (95% CI 4.6-6.7%) and late ARMD for 0.4% (95% CI 0.2-0.8%). Multivariate analysis showed that ARMD prevalence increased significantly with age (OR per year 1.08; 95% CI 1.05-1.11, p<0.001) and in the male sex (OR 1.57; 95% CI 1.01-2.44, p=0.043). The other traditional ARMD risk factors did not show significant associations in this cohort. Compared to other European populations, ARMD prevalence was notably lower.<br><br>CONCLUSION: This study reports a relatively low prevalence of ARMD compared to other European settings, with age and male sex emerging as the only significant risk factors. The absence of association with other traditional risk factors may reflect underlying genetic differences or distinct gene-environment interactions. As DNA samples were collected, further investigation incorporating genetic data is warranted to better understand ARMD susceptibility in this population.},
}
@article {pmid41179910,
year = {2026},
author = {Doshi, U and Davis, E and Al-Sheikh, M and Sahel, JA and Chhablani, J and Vupparaboina, KK and Bollepalli, SC},
title = {Generalizable Multimodal Retinal Image Registration via Label-free Vessel Segmentation.},
journal = {Biomedical signal processing and control},
volume = {113},
number = {Pt B},
pages = {},
pmid = {41179910},
issn = {1746-8094},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; },
abstract = {Multimodal retinal imaging plays a crucial role in diagnosing and managing various retinal diseases such as diabetic retinopathy and age-related macular degeneration (AMD). The majority of retinal imaging modalities including Color Fundus Photography (CF), Fluorescein Angiography (FAG), Fundus Autofluorescence (FAF), Indocyanine Green Angiography (ICG), and Optical Coherence Tomography (OCT), along with infrared imaging (IR) and B-scans, capture different aspects of the same pathology within the retina. Consequently, accurate disease quantification, monitoring, and automated diagnosis require integrating their complementary insights, which relies on accurate registration of these images. To this end, developing a robust registration algorithm applicable across all modalities assumes significance. This paper presents a generalizable, label-free approach to retinal image registration, using vessel structure, extracted using DexiNed algorithm. The proposed method was evaluated across various imaging modalities, including CF-IR, CF-FAF, CF-FAG, CF-ICG, FAF-FAG, FAF-ICG, and FAG-ICG, achieving a mean landmark error (MLE) ranging from 1.91±0.44 to 4.9±2.32 pixels. In particular, CF-IR and CF-FAF registration attained an MLE of 3.08±1.47 and 4.9±2.32 pixels respectively, performing favorably when compared to human grader annotations. Furthermore, the proposed solution eliminates the need for large labeled training datasets while effectively extracting vessel structures to enable multimodal retinal image registration, improving diagnostic precision and disease monitoring.},
}
@article {pmid41178994,
year = {2025},
author = {Li, Y and Wang, C and Deng, T and Li, X and Xu, R and Shang, Q},
title = {RARRES1 attenuates H2O2-induced RPE cell injury and inhibits choroidal neovascularization.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1641653},
pmid = {41178994},
issn = {1664-042X},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in the elderly, yet its underlying molecular mechanisms remain incompletely understood, and novel biomarkers and therapeutic targets are urgently needed. This study aimed to identify and functionally characterize potential biomarkers and therapeutic candidates for nAMD, with a focus on retinoic acid receptor responder protein 1 (RARRES1).<br><br>METHODS: Tandem mass tag (TMT)-based proteomic analysis was performed on aqueous humor samples from patients with nAMD and age-related cataracts. RARRES1 expression was examined in aqueous humor, laser-induced choroidal neovascularization (CNV) model mice, and human ARPE-19 cells exposed to H2O2. Functional studies assessed the effects of RARRES1 on oxidative stress, cell death, inflammatory and angiogenic factor expression, and signaling pathways in ARPE-19 cells. Its effects on proliferation, migration, and tube formation were tested in HUVECs. In vivo, a RARRES1-overexpressing AAV2 vector was injected intraocularly into CNV model mice, and lesion size and vascular leakage were evaluated using fundus fluorescein angiography, hematoxylin and eosin staining, and isolectin B-4 fluorescence staining.<br><br>RESULTS: RARRES1 was significantly reduced in the aqueous humor of nAMD patients, in CNV model mice, and in H2O2-treated ARPE-19 cells. Overexpression of RARRES1 in ARPE-19 cells mitigated oxidative stress-induced damage, suppressed inflammatory and angiogenic factor expression, inhibited JNK phosphorylation, and increased Sirtuin 1 and Nrf2 expression. In HUVECs, RARRES1 reduced proliferation, migration, and tube formation. In vivo, intraocular delivery of RARRES1 significantly reduced CNV lesion size and vascular leakage.<br><br>CONCLUSION: RARRES1 protects retinal pigment epithelial cells from oxidative stress, inhibits choroidal neovascularization, and modulates inflammatory and angiogenic pathways. These findings identify RARRES1 as a potential biomarker and therapeutic target for nAMD.},
}
@article {pmid41177553,
year = {2025},
author = {Sawires, K and Nithianandan, H and Somani, S},
title = {Comparative outcomes of aflibercept biosimilars and reference aflibercept in nAMD: a systematic review and meta-analysis.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {41177553},
issn = {2397-3269},
mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; *Visual Acuity ; Randomized Controlled Trials as Topic ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; },
abstract = {OBJECTIVE: To evaluate the literature-pooled functional, anatomical and safety outcomes of aflibercept biosimilars compared with reference aflibercept for neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSIS: Systematic review and meta-analysis. Medline, Embase and CENTRAL were searched from inception to 2 June 2025. Phase 3 randomised controlled trials (RCTs) comparing aflibercept biosimilars with the reference product in patients with nAMD were included. Two independent reviewers conducted screening, data extraction, risk of bias (RoB 2) assessment and certainty of evidence assessment (Grading of Recommendations, Assessment, Development and Evaluation), with a third reviewer resolving discrepancies. Primary outcomes included mean difference (MD) change in best-corrected visual acuity (BCVA) and retinal thickness over time, risk ratio (RR) for proportion of participants gaining >15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and RR for adverse events. Meta-regression was used to evaluate the temporal stability of continuous outcomes.<br><br>RESULTS: Six RCTs involving 2044 participants (1026 biosimilar, 1018 reference) were included. Five aflibercept biosimilars were evaluated, representing more than 50% of the eight biosimilars currently approved worldwide. Meta-regression revealed no significant difference in MD change in BCVA over time between biosimilar and reference aflibercept (slope: 0.0321 letters/week; p=0.1013). For MD change in retinal thickness, an initial anatomical advantage for reference aflibercept at week 0 (intercept: 9.58&#x2009;&#xb5;m; p=0.0449) was not sustained over time (slope: -0.1685&#x2009;&#xb5;m/week; p=0.2303). The pooled RR for gaining >15 ETDRS letters from baseline was 1.19 (95% CI 0.98 to 1.45; p=0.079). No statistically significant differences were observed across 15 safety outcomes.<br><br>CONCLUSION: This systematic review and meta-analysis found no statistically significant differences in functional, anatomical or safety outcomes between aflibercept biosimilars and the reference product for nAMD, based on moderate to high certainty evidence. Functional and anatomical outcomes appeared stable across multiple timepoints. Further long-term pharmacovigilance studies and real-world data beyond 56 weeks are warranted.<br><br>PROSPERO REGISTRATION NUMBER: CRD420251048633.},
}
@article {pmid41177551,
year = {2025},
author = {Brunner, P and Havanur, P and Papukchieva, S and Friedrich, B and Ziemssen, F},
title = {Tracking real-world persistence and adherence to anti-VEGF intravitreal therapy with prefilled syringes: a German prescription sales analysis.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {41177551},
issn = {2397-3269},
mesh = {Humans ; Germany/epidemiology ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Female ; Aged ; *Syringes ; *Drug Prescriptions/statistics &amp; numerical data ; *Bevacizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; *Ranibizumab/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Follow-Up Studies ; },
abstract = {OBJECTIVE: Intravitreal antivascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration and other retinal vascular diseases. Despite proven efficacy in clinical trials, real-world data suggest suboptimal persistence and adherence. This study aimed to assess therapy continuity in routine practice using pharmacy-based dispensing data in Germany, focusing on treatment with prefilled syringes (PFS).<br><br>METHODS AND ANALYSIS: This retrospective cohort study used anonymised nationwide pharmacy sales data from Germany to evaluate patients who initiated anti-VEGF therapy with PFS between 2020 and 2023. Patient trajectories were followed from treatment initiation for up to 12 months. 46&#x2009;546 therapy beginners with 297&#x2009;454 anti-VEGF PFS purchases were included. Discontinuation of treatment was defined by not purchasing a relevant medication for >6 months.<br><br>RESULTS: Mean time on therapy for all patients was 8.1&#xb1;8.2 months (median=5.5) with 6.9&#xb1;6.1 purchases (median=5). 20.5% of patients initiating anti-VEGF treatment stopped therapy before completing the loading phase (first three injections), and more than half of all patients discontinued treatment after 6 months. 49.4% of the patients who completed the loading phase (n all=34&#x2009;895) adhered to the recommended monthly regimen. Non-adherence significantly decreased the number of injections later on (average of 7.5 vs 8.7 injections). Further, patients who stayed longer on therapy bought more PFSs within the first 6 and 12 months.<br><br>CONCLUSIONS: Real-world adherence and persistence to intravitreal anti-VEGF therapy in Germany are suboptimal, even with the use of PFS formulation. The high rate of early treatment discontinuation, especially during the loading phase, underscores the need for improved patient support, education and flexible treatment approaches to sustain long-term outcomes. A 'breaking point' or sensitive phase already seems to exist right at the beginning of therapy.},
}
@article {pmid41175863,
year = {2025},
author = {Xin, Y and Jin, Y and Qian, C and Blackshaw, S and Qian, J},
title = {MetaLigand provides a prior-knowledge-guided framework for predicting non-peptide ligand mediated cell-cell communication.},
journal = {Cell reports methods},
volume = {5},
number = {11},
pages = {101217},
pmid = {41175863},
issn = {2667-2375},
mesh = {*Cell Communication ; Humans ; Ligands ; Transcriptome ; Animals ; *Computational Biology/methods ; },
abstract = {Non-peptide ligands (NPLs), including lipids, amino acids, carbohydrates, and non-peptide neurotransmitters and hormones, play a critical role in ligand-receptor-mediated cell-cell communication, driving diverse physiological and pathological processes. To facilitate the study of NPL-dependent intercellular interactions, we introduce MetaLigand, a tool designed to infer NPL availability and NPL-receptor interactions using transcriptomic data. MetaLigand compiles data for 233 NPLs, including their biosynthetic enzymes, transporter genes, and receptor genes, through a combination of automated pipelines and manual curation from comprehensive databases. The tool integrates both de novo and salvage synthesis pathways, incorporating multiple biosynthetic steps and transport mechanisms. Comparisons with existing tools demonstrate MetaLigand's ability to account for complex biogenesis pathways and model NPL availability across diverse tissues and cell types. Furthermore, analysis of single-nucleus RNA sequencing (RNA-seq) datasets from age-related macular degeneration samples revealed that distinct retinal cell types exhibit unique NPL profiles and participate in specific NPL-mediated pathological cell-cell interactions.},
}
@article {pmid41175224,
year = {2025},
author = {Yang-Seeger, D and Schellstede, A and Pauleikhoff, LJB and Spitzer, MS and Birtel, J},
title = {Travel-associated emissions of intravitreal injections.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41175224},
issn = {1435-702X},
abstract = {PURPOSE: Intravitreal injections (IVIs) are among the most frequently performed ophthalmic procedures and have been associated with a substantial carbon footprint. Travel-associated emissions are considered a key driver of IVIs' carbon footprint; however, no study in a country with a decentralised healthcare system has assessed IVI-related emissions. Here, the IVI-associated carbon footprint in an urban German tertiary referral centre was investigated.<br><br>METHODS: In total, 340 patients were included. The carbon footprint was assessed based on the distance travelled by patients and accompanying persons, the mode of transport, and postoperative follow-up visits. Demographic data, treatment indication, and the injected medication were collected.<br><br>RESULTS: The average travel-associated CO2 equivalent (CO2eq) for a single IVI was 11.1&#xa0;kg. Of this,&#xa0;9.1&#xa0;kg CO2eq and 2&#xa0;kg CO2eq were due to travel to the injection clinic and to follow-up visits, respectively. Anti-VEGF treatment for common diseases such as age-related macular degeneration and diabetic macular edema was associated with a lower CO2eq compared with treatment of patients suffering from&#xa0;less prevalent conditions such as uveitis (10.8&#xa0;kg vs. 15.6&#xa0;kg). The majority of patients (49%) travelled by public transport (median distance: 22.4&#xa0;km); patients travelling by car (33%) usually covered longer distances (median distance: 61.5&#xa0;km).<br><br>CONCLUSION: Travel is a meaningful contributor to the carbon footprint of IVIs. Mitigation may be achieved by various approaches, such as longer-acting therapeutic agents or bilateral injections. To implement strategies for more sustainable IVIs, ophthalmologists may be encouraged by local and national bodies to incorporate environmental criteria into their practice.},
}
@article {pmid41174770,
year = {2025},
author = {Trinh, M and Tee, YG and Nam, J and Chen, S and Schiller, G and Friedrich, J and Ng, D and Ly, A and Hodge, C and Nivison-Smith, L},
title = {Localising OCTA changes induced by the isometric hand-grip test to the superficial retina in neovascular age-related macular degeneration.},
journal = {Eye and vision (London, England)},
volume = {12},
number = {1},
pages = {44},
pmid = {41174770},
issn = {2326-0254},
support = {2023//Future Vision Foundation/ ; },
abstract = {PURPOSE: This study uses optical coherence tomography angiography (OCTA) topographical cluster analysis to localise where vascular changes occur during the isometric hand-grip test (IHGT) in eyes with neovascular age-related macular degeneration (AMD).<br><br>METHODS: This prospective study included single eyes from 44 participants with neovascular&#xa0;AMD. Systemic blood pressure (BP) and macular 6&#x2009;&#xd7;&#x2009;6&#xa0;mm OCTA scans were obtained before the IHGT, during the IHGT, and after the IHGT. The main outcome was the change in processed OCTA signal (%), measured within high-density (126&#x2009;&#xd7;&#x2009;126) grids and analysed by topographical clusters across the superficial retina, deep retina, and choriocapillaris. Results were compared against test-retest thresholds to differentiate true IHGT-induced changes from measurement variability.<br><br>RESULTS: The IHGT increased systolic (13.83 [3.28, 24.39] mmHg) and diastolic BP (7.04 [3.57, 10.52] mmHg; P&#x2009;<&#x2009;0.01). Adjusted for test-retest thresholds, the IHGT increased processed OCTA signal (12.84 [8.49, 26.77] %, P&#x2009;<&#x2009;0.0001) at nasal clusters in the superficial retina. These changes were moderately correlated with systolic BP increases (Spearman r&#x2009;=&#x2009;0.43, P&#x2009;<&#x2009;0.05), but not with diastolic BP. No changes were observed in the deep retina or choriocapillaris. Systemic BP and processed OCTA signal returned to baseline within 30&#xa0;s after IHGT release.<br><br>CONCLUSION: Hand-squeezing temporarily increases processed OCTA signal in the nasal superficial retina. This response may serve as a valuable marker of vascular function. Consequently, caution is warranted when interpreting OCTA following BP changes, such as those induced by physical activity or medication changes.},
}
@article {pmid41173219,
year = {2025},
author = {Deimazar, G and Sabbaghi, H and Ahmadieh, H and Sheikhtaheri, A},
title = {Artificial intelligence for detection of age-related macular degeneration based on fundus images: A systematic review.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.10.004},
pmid = {41173219},
issn = {1879-3304},
abstract = {Age-related macular degeneration (AMD) is one of the most common types of eye diseases that generally affect the elderly population over 50 years of age. The effects of AMD on the quality of vision and life are devastating. We systematically review applications and performance of machine/deep learning algorithms for AMD detection and prediction using color fundus photos. We reviewed the studies that focused on machine learning and deep learning techniques and algorithms to analyze the fundus images for AMD. The data were collected by searching Scopus, PubMed (Medline), Web of Science and IEEE Xplore databases. After screening, 42 papers were included. The findings showed that the studies used different architectures for model training and testing. Convolutional neural networks (CNN) are used mostly in the diagnosis of AMD. ResNet architecture (11 studies) was used more than other architectures. Twenty-two studies used AREDS dataset. CNN algorithm with ResNet architecture had the highest performance compared to other architectures. Studies have shown that machine learning can diagnose AMD from fundus images with high accuracy; however, calibration, fairness, explainability, external validation, generalization, prospective validation in clinical settings and regulatory requirements should be considered in the future.},
}
@article {pmid41172710,
year = {2025},
author = {Singh, S and Runyon, W and Hu, S and Kennedy, PG and Singh, A and Ratnapriya, R and Kumar, R and Csaky, K and Sripathi, SR},
title = {Generation of iPSCs (RFSCi007-A, RFSCi008-A) from a patient with early-onset bilateral drusen and a healthy sibling for retinal disease modeling.},
journal = {Stem cell research},
volume = {89},
number = {},
pages = {103862},
doi = {10.1016/j.scr.2025.103862},
pmid = {41172710},
issn = {1876-7753},
abstract = {Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.},
}
@article {pmid41170269,
year = {2025},
author = {Lloyd, A and Elbalawi, M and Kurc, M and Hussain, M and Abugreen, S},
title = {The Implementation of Faricimab in East Lancashire NHS Trust: Highlighting the Real-World Efficacy and Safety in Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93478},
pmid = {41170269},
issn = {2168-8184},
abstract = {PURPOSE: To report the safety and efficacy of intravitreal faricimab injections (IVTF) in both treatment-naïve and treatment-resistant patients with neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This study was a retrospective real-world evidence trial where patients with nAMD were given IVTF. Group 1 (treatment-na&#xef;ve) and group 2 (switch loading dose, SLD)&#xa0;were given a course of four loading doses of IVTF four weeks apart. Group 3 (switch pro re nata, SPRN)&#xa0;was given a single IVTF and then reviewed at eight weeks. The outcome was based on visual acuity (VA) and optical coherence tomography (OCT), showing central retinal thickness (CRT), subretinal, and intraretinal fluid.<br><br>RESULTS: A total of 99 eyes from 89 patients were included. A total of 350 IVTF were given. The mean follow-up duration was 6.33 &#xb1; 1.11 months (range: 2-8 months).&#xa0;The mean change in CRT at final follow-up was&#xa0;-127.09 &#xb1; 97.39 &#xb5;m (p < 0.001) for na&#xef;ve eyes, -115.59 &#xb1; 145.02 &#xb5;m (p < 0.001) for SLD, and -57.61 &#xb1; 58.06 &#xb5;m (p < 0.001) for SPRN. The mean VA change was&#xa0;-3.47 ETDRS (Early Treatment Diabetic Retinopathy Study) (p = 0.256) for na&#xef;ve eyes, -0.79 (p = 0.45) for SLD, and +1.25 (p = 0.304) for SPRN. A total of 48 eyes (48.48%) had better VA, 22 (22.22%) had no change in VA, and 29 (29.29%) had worse VA. One patient developed bilateral sterile intraocular inflammation.<br><br>CONCLUSION: IVTF was associated with an improvement in CRT in both treatment-naive and treatment-resistant nAMD patients. There was no evidence of vasculitis or vein occlusion, highlighting the safety of faricimab in our real-world study.},
}
@article {pmid41169746,
year = {2025},
author = {Abuleil, D and Gorbet, D and McCulloch, DL and Cohan, R and Steeves, JEK and Bang, JW and Chan, KC and Thompson, B},
title = {Anodal transcranial direct current stimulation does not alter GABA concentration or functional connectivity in the normal visual cortex.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1639838},
pmid = {41169746},
issn = {1662-4548},
abstract = {INTRODUCTION: Anodal direct current stimulation (a-tDCS) of the visual cortex is a potential rehabilitation tool for vision disorders such as amblyopia and macular degeneration. However, the underlying neural mechanisms are currently unknown. When applied to the human motor cortex, a-tDCS reduces the concentration of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that modulates neuroplasticity. Our primary aim was to assess whether the same a-tDCS paradigm alters local GABA concentration when applied to the healthy primary visual cortex. We also measured the effect of a-tDCS on visual cortex resting-state connectivity and sought to replicate reported observations of an association between visual cortex GABA concentration and the dynamics of binocular rivalry.<br><br>METHODS: Fourteen participants with normal vision completed two brain imaging sessions at least 48 hours apart. In each session, binocular rivalry dynamics, primary visual cortex GABA and glutamate-glutamine (Glx) concentrations (via magnetic resonance spectroscopy (MRS)) and resting-state functional connectivity (via task-free fMRI) were measured at baseline. Real or sham a-tDCS (20 min, 2mA) was then applied to the visual cortex in a randomized sequence followed by a second set of MRS and fMRI measurements.<br><br>RESULTS: No between-session effects of a-tDCS on GABA or Glx concentration or resting-state functional connectivity were observed. A pre-planned within-session analysis revealed a significant increase in Glx following a-tDCS that did not withstand multiple comparisons correction. No consistent relationships between binocular rivalry dynamics and GABA concentration were apparent.<br><br>DISCUSSION: Together, our results suggest that a-tDCS effects on the visual cortex may differ from the GABA-associated mechanism in motor cortex.},
}
@article {pmid41169217,
year = {2025},
author = {Mirshahvaladi, S and Gaire, BP and Kashani, SA and Guha, A and Koronyo, Y and Fuchs, DT and You, Y and Black, KL and Paulo, JA and Graham, SL and Gupta, V and Mirzaei, M and Koronyo-Hamaoui, M},
title = {Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00291},
pmid = {41169217},
issn = {1673-5374},
abstract = {Dysregulated proteome in the retina represents a promising avenue for discovering novel therapeutic targets and noninvasive diagnostic biomarkers for neurodegenerative diseases with ocular manifestations. Advanced mass spectrometry-based proteomics techniques have shown considerable potential in investigating the retinal proteome in diseases such as glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, as well as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Recent proteomics innovations are overcoming challenges such as limited sample size and protein coverage that previously hindered comprehensive retinal proteome analysis. Notably, the incorporation of artificial intelligence-driven computational pipelines, including Graphics Processing Unit-accelerated deep learning architectures, has markedly enhanced the precision and effectiveness of retinal proteomics. These advances facilitate high-resolution identification of novel protein signatures within large-scale multi-omics datasets. Furthermore, the integration of advanced artificial intelligence with state-of-the-art big data infrastructures supports the early detection of biomarkers and therapeutic targets in neurodegenerative diseases with ocular involvement, offering unprecedented disease specificity and sensitivity. In addition to these computational strides, emerging complementary and alternative technologies continue to provide valuable tools for retinal analysis, expanding the potential for identifying biomarker and therapeutic targets in both ophthalmic and neurodegenerative disorders. This review summarizes recent advancements in retinal proteomics, with a particular focus on neurodegenerative and ocular diseases.},
}
@article {pmid41168502,
year = {2025},
author = {Jiménez-Loygorri, JI and Shang, P and Bayramoglu, I and Gómez-Sintes, R and Martín-Segura, A and Ambrosino, H and Hoang, J and Díaz, A and Geng, Z and Gavathiotis, E and Dutton, JR and Dengjel, J and Cuervo, AM and Ferrington, DA and Boya, P},
title = {Defective chaperone-mediated autophagy in the retinal pigment epithelium of age-related macular degeneration patients.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41168502},
issn = {1757-4684},
support = {310030_215271//SNSF/ ; 310030_212187//SNSF/ ; CRSII5_189952//SNSF/ ; PID2021-126864NBI00//MCIN/ ; PRE2019-088222//MCIN/ ; R01EY028554//NIH/NEI/ ; AG021904//NIH/NIA/ ; AG031782//NIH/NIA/ ; Ram&#xf3;n Areces Postdoctoral Fellowship//Ramon Areces Foundation/ ; },
abstract = {Autophagy is one of the main intracellular recycling systems and its impairment is considered a primary hallmark of the aging process. Defective macroautophagy in the retinal pigment epithelium (RPE) has been described in age-related macular degeneration (AMD), a blindness-causing disease that affects roughly 200 million patients worldwide. The relevance of chaperone-mediated autophagy (CMA), a selective type of autophagy for proteins containing a KFERQ-like motif, in RPE cell biology and homeostasis remains to be elucidated. Here we describe decreased CMA activity in the RPE of AMD patients compared to healthy age-matched controls, along with accumulation of substrate proteins, and in donor-derived iPSC-RPE cells, which we used to further characterize AMD-associated alterations of cellular homeostasis derived from proteotoxicity. Treatment with CA77.1 (CMA activator) restores proteostasis and remodels specific subsets of the proteome in cells from healthy and AMD donors. CA77.1-treated AMD iPSC-RPE display reduced oxidative stress and improved mitochondrial function. These findings may explain the specific vulnerability of the RPE during AMD and shed light on CMA as a new druggable target for this as-of-now incurable disease.},
}
@article {pmid41168499,
year = {2025},
author = {Fink, DJ and Finger, RP and Terheyden, JH},
title = {[Importance of vision in old age].},
journal = {Zeitschrift fur Gerontologie und Geriatrie},
volume = {58},
number = {8},
pages = {639-644},
pmid = {41168499},
issn = {1435-1269},
mesh = {Humans ; Aged ; *Vision Disorders/diagnosis/therapy/rehabilitation/prevention &amp; control/psychology ; Aged, 80 and over ; Female ; Male ; *Quality of Life/psychology ; Germany ; },
abstract = {Vision is a significant determinant of quality of life and autonomy in older people. It declines with age due to natural processes. In the general population this is exacerbated by age-related eye diseases, such as cataract, age-related macular degeneration, glaucoma and diabetic retinopathy. The resulting impairments can lead to reduced mobility, independence and mental health and physiological ageing processes of the eye and disease-related changes in visual function are therefore associated with increased morbidity, such as an increased risk of falls and depression. Treatment, prevention and rehabilitation measures can significantly reduce the impairment of older people caused by age-related eye diseases. In order to keep pace with the increasing demand for care and to maintain vision at the highest possible level into old age, not only targeted and timely ophthalmological care are necessary but also more prevention in the field of age-related eye diseases.},
}
@article {pmid41167797,
year = {2025},
author = {Huang, X and Chen, J and Li, J and Zhang, G and Zhu, X and Zhou, M and Bo, Q and Sun, X},
title = {Choroidal changes correlate with type 1 neovascular activity in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327839},
pmid = {41167797},
issn = {1468-2079},
abstract = {PURPOSE: To investigate the association among choroidal factors and lesion activity of polypoidal choroidal vasculopathy (PCV) and type I neovascular age-related macular degeneration (nAMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: 69 eyes with PCV or type I nAMD were retrospectively included. All eyes had either &#x2265;2 consecutive non-exudative visits without treatment or no exudation/treatment within 6-month SS-OCTA follow-up. Lesions were categorised into active and inactive based on progression, defined as exudation, branching vascular network (BVN)/macular neovascularisation enlargement or recurrence/new/growth of polypoidal lesions. Choroidal parameters, including mean choroidal thickness (MCT), choroidal vascularity index (CVI) and choroidal volume (CV), were evaluated before and after lesion progression. The association between CVI variation and lesion area growth in PCV was also analysed.<br><br>RESULTS: No baseline differences in MCT or CVI were found between PCV and nAMD. However, significant differences in CVI and MCT variation were observed between active and inactive lesions (p<0.05). In PCV, lesion activity was characterised by decreased CVI and increased MCT, while in nAMD, only MCT and CV increased. Notably, combined CVI decrease and MCT increase served as a sensitive marker for active PCV (p<0.05), but not for nAMD. CVI reduction also correlated with BVN growth in PCV (R=-0.722, p<0.01).<br><br>CONCLUSION: Choroidal parameters varied significantly during lesion progression. Combined CVI decrease and MCT increase sensitively reflected active PCV lesions and were correlated with lesion location, size and progression, highlighting the differences in the choroidal microenvironment in the activities of PCV and nAMD.},
}
@article {pmid41167282,
year = {2025},
author = {Chen, Y and Jiang, F and Zhang, M},
title = {Response to comments on refining the translational pathway for senotherapeutics in age-related macular degeneration: Insights on biomarkers, delivery strategies, and clinical trial design.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.10.006},
pmid = {41167282},
issn = {1879-3304},
}
@article {pmid41166891,
year = {2025},
author = {Zhang, M and Shen, J and Luly, KM and Lim, Y and Shannon, SR and Jain, M and Tzeng, SY and Hackett, S and Kanan, Y and Green, JJ and Campochiaro, PA},
title = {Suppression of choroidal neovascularization by nonviral gene transfer of pigment epithelium-derived factor.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {193},
number = {},
pages = {118711},
doi = {10.1016/j.biopha.2025.118711},
pmid = {41166891},
issn = {1950-6007},
abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss among individuals over 60, is characterized by progressive retinal degeneration in a critical area for vision, the macula, and neovascular complications. Pigment epithelium-derived factor (PEDF) has the potential to address both of these pathologic processes because it has both neuroprotective and anti-angiogenic activities. In this study, we used a polymeric nonviral gene transfer platform to express PEDF in the eyes of mice and rats. In mice, there was high expression of PEDF in the retina and eyecup two weeks after subretinal injection of poly(β-amino ester) (PBAE) nanoparticles (NPs) containing a plasmid encoding PEDF, and at 2 or 4 weeks after injection there was a significant reduction in the area of choroidal neovascularization (CNV) at Bruch's membrane rupture sites compared with eyes that had received subretinal injection of a control vector. As suprachoroidal injection is a route of vector delivery that can be done in an outpatient setting and may limit certain negative side effects associated with subretinal injection, this route of administration was also investigated for PEDF plasmid delivery. In rats, there was high expression of PEDF in the retina and eyecup 4 weeks after suprachoroidal injection of PEDF NPs, and a significant reduction in CNV area at Bruch's membrane rupture sites compared with those in eyes injected with control vector. These data suggest that ocular nonviral gene transfer of PEDF may provide a new treatment approach for AMD.},
}
@article {pmid41165404,
year = {2025},
author = {Faurite, C and Michaud, C and Cousin, E and Olivier, P and Gallice, M and Chiquet, C and Pietras, J and Attyé, A and Soler, V and Berry, I and Mermillod, M and Cottereau, BR and Peyrin, C},
title = {Neurobehavioral Changes in Macular Degeneration: Spatial Frequency Use in Scene Recognition.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {13},
pages = {54},
pmid = {41165404},
issn = {1552-5783},
mesh = {Humans ; *Macular Degeneration/physiopathology/psychology ; Male ; Female ; Magnetic Resonance Imaging ; Aged ; Middle Aged ; *Scotoma/physiopathology ; *Pattern Recognition, Visual/physiology ; Visual Acuity/physiology ; *Visual Perception/physiology ; Aged, 80 and over ; },
abstract = {PURPOSE: Central vision loss in macular diseases severely affects visual perception and cognition, particularly scene recognition. A key question is whether observed impairments result solely from reduced input or reflect functional changes in spatial frequency processing. This study investigated how macular diseases affects this processing at both behavioral and brain levels.<br><br>METHODS: We compared patients with macular diseases with age-matched controls using an artificial scotoma simulating each patient's central vision loss. Participants performed a scene categorization task with images filtered in high spatial frequencies (HSFs; fine details) or low spatial frequencies (LSFs; global shape). Patients fixated using their preferred retinal locus (PRL), whereas controls fixated on the location corresponding to the patient's fovea, within the artificial scotoma. Behavioral performance and functional magnetic resonance imaging (fMRI) responses were analyzed.<br><br>RESULTS: Patients performed worse than the healthy controls for both HSF and LSF scenes, with a more pronounced deficit for HSFs. These deficits were associated with reduced activation in occipital cortex and in the parahippocampal place area (PPA), particularly for HSF scenes. In contrast, LSF processing was relatively preserved and accompanied by increased recruitment of higher-level cognitive and oculomotor areas in patients.<br><br>CONCLUSIONS: These findings demonstrate that macular diseases leads to altered spatial frequency processing within residual vision itself, particularly affecting fine-detail analysis. This perceptual degradation is accompanied by functional brain reorganization supporting partial compensation. The results highlight the importance of considering both degraded input and adaptive mechanisms when designing rehabilitation strategies based on residual peripheral vision.},
}
@article {pmid41164518,
year = {2025},
author = {Namdeo, TS and Ashok, AA},
title = {Transformative Algal Interventions in Ophthalmology, Mechanisms, and Future Potential: A Review.},
journal = {Journal of pharmacy &amp; bioallied sciences},
volume = {17},
number = {Suppl 3},
pages = {S2044-S2048},
pmid = {41164518},
issn = {0976-4879},
abstract = {Microalgae have become the focus of many studies concerning ocular health due to the varied chemical composition of algae. These organisms contain bioactive compounds especially carotenoids, polyunsaturated fatty acids (PUFAs), and antioxidants, which have proven beneficial in some diseases of the eyes. This review is focused on summarizing the potential therapeutic use of algae in treating eye diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR), and dry eye syndrome. We will also describe the pathways by which algae produce benefits, review cases of clinical studies, and explore future uses for algae in treatments.},
}
@article {pmid41162760,
year = {2025},
author = {Brandl, C and Schuster, AK and Finger, RP},
title = {[Nutrition and dietary supplements in eye diseases-Part 1: age-related macular degeneration and diabetic eye diseases].},
journal = {Die Ophthalmologie},
volume = {122},
number = {11},
pages = {871-872},
doi = {10.1007/s00347-025-02326-3},
pmid = {41162760},
issn = {2731-7218},
}
@article {pmid41162529,
year = {2025},
author = {Misson, GP and Anderson, SJ and Armstrong, RA and Heitmar, R},
title = {A novel computational model for human macular pigment optical density and its relationship to foveal structure.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {37865},
pmid = {41162529},
issn = {2045-2322},
mesh = {Humans ; *Macular Pigment/metabolism ; *Fovea Centralis/diagnostic imaging/metabolism ; Tomography, Optical Coherence ; Female ; Male ; Macular Degeneration/metabolism/diagnostic imaging ; Aged ; Middle Aged ; *Computer Simulation ; Xanthophylls/metabolism ; Macula Lutea/metabolism ; },
abstract = {Macular pigment optical density (MPOD) models enhance understanding of macular xanthophyll distribution, particularly relevant to age-related macular degeneration. This study investigates an existing model and introduces a novel, more accurate and biologically relevant approach. MPOD spatial profiles of 48 eyes were obtained using dual-wavelength autofluorescence imaging, with structural data from OCT and OCT-angiography. MPOD data were analyzed using (a) an existing sum of exponential and Gaussian model (MEG) and (b) a novel sum of three Gaussians model (M3G). Extracted parameters generated individualized MPOD models, from which gradients and volumes were derived. M3G-derived variables were analyzed against OCT/OCTA data using factor analysis and multiple regression. M3G demonstrated a superior fit to MPOD data (SSE = 2.60 × 10[- 3]) compared to MEG, (SSE = 35.7 × 10[- 3]) enabling automated fitting consistent over small and large datasets. M3G provided meaningful variables, including MPOD gradients, volumes and critical point eccentricities. Correlations included those between dependent variables of critical point eccentricities and central macular pigment volume with foveal avascular zone and foveal pit radii.The excellent data fit of M3G enables automated extraction of physiologically relevant parameters. Its three-component configuration is consistent with the location of macular xanthophylls. M3G is similar to models of foveal structure, suggesting a fundamental relationship.},
}
@article {pmid41162502,
year = {2025},
author = {Luo, M and Zhang, M and Xing, Z and Yu, W and Lv, H},
title = {Mechanistic analysis of luteolin in mitigating dry age-related macular degeneration through network pharmacology and experimental validation.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {37862},
pmid = {41162502},
issn = {2045-2322},
support = {2024ZYD0114//Sichuan Provincial Department of Science and Technology/ ; S2024001//Sichuan Medical Association/ ; },
mesh = {*Luteolin/pharmacology/chemistry ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; Molecular Docking Simulation ; *Network Pharmacology ; Cell Survival/drug effects ; Protein Interaction Maps/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; Retinal Pigment Epithelium/drug effects/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Iodates ; },
abstract = {Dry age-related macular degeneration (AMD) ranks among the primary causes of irreversible vision loss in the elderly. Luteolin, with its diverse biological activities, has attracted significant attention as a promising candidate for intervening in dry AMD. Explore the protective effect of luteolin on dry AMD to address the unmet need for current therapeutic agents. Luteolin's target information and dry AMD-related genes were retrieved from public databases. Shared targets of luteolin and dry AMD were used to construct a protein‒protein interaction network, followed by Gene Ontology and pathway enrichment analyses. Finally, molecular docking between the active ingredient and core targets was validated. In vitro, sodium iodate was used to induce ARPE-19 cells, after which cell viability was analyzed via a Cell Counting Kit-8 (CCK-8) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential were detected via fluorescent dye staining. In the network pharmacology analysis, a total of 213 potential therapeutic targets associated with luteolin's activity against dry AMD were identified. Among these genes, TP53, TNF, IL6, AKT1, BCL2, STAT3, JUN, and CASP3 were identified as core therapeutic targets. These targets are primarily involved in pathways including lipid and atherosclerosis, cancer-related pathways, and the AGE-RAGE signaling pathway in diabetic complications. Molecular docking analyses revealed strong binding affinities between luteolin and the core targets, validating the molecular mechanisms underlying luteolin's efficacy against dry AMD. Experimental data demonstrated that luteolin not only mitigated sodium iodate-induced reductions in ARPE-19 cell viability but also decreased intracellular ROS levels and restored mitochondrial membrane potential. Luteolin effectively enhances the viability of damaged RPE cells, reduces oxidative stress levels, and protects mitochondrial function. This protective effect is likely mediated through the coordinated action of multiple targets and pathways, highlighting luteolin's promising potential in the prevention and management of dry AMD. However, this study is limited by its sole reliance on in vitro cell validation and inability to fully reflect real in vivo effects and potential side effects.},
}
@article {pmid41162371,
year = {2025},
author = {Amirkavei, M and Kaikkonen, O and Turunen, T and Meller, A and Åhlgren, J and Kvanta, A and André, H and Koskelainen, A},
title = {Non-damaging laser treatment with electroretinography-based thermal dosimetry activates hormetic heat response in pig retinal pigment epithelium.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9533},
pmid = {41162371},
issn = {2041-1723},
mesh = {Animals ; *Retinal Pigment Epithelium/radiation effects/metabolism/pathology ; *Electroretinography/methods ; Swine ; Male ; *Heat-Shock Response/physiology ; *Laser Therapy/methods ; Autophagy/radiation effects ; Apoptosis/radiation effects ; Oxidative Stress ; Retina ; Lasers ; Hot Temperature ; Heat-Shock Proteins/metabolism ; },
abstract = {Enhancing protein homeostasis and antioxidant defense mechanisms in the retinal pigment epithelium (RPE) holds significant promise as a treatment option for various retinal diseases, including age-related macular degeneration. However, patient responses to laser-induced RPE hyperthermia varies substantially. To address this, we introduce a focal electroretinography (fERG)-based method for retinal temperature monitoring during laser exposure. Applying the method to anaesthetized male pigs in vivo, we study the biological effects of controlled retinal hyperthermia. Our findings reveal that temperature elevation to 44 °C with 60-second laser exposure triggers heat shock protein production and autophagy activation in RPE/choroid while avoiding oxidative stress, apoptosis, and structural damage. Importantly, our results demonstrate that visible lesions occur at temperatures above 48 °C, and that the temperature determination precision was 0.6 °C. These outcomes highlight that fERG-controlled retinal laser treatment enables reliable and safe activation of cytoprotective mechanisms in the RPE, providing a promising new therapeutic approach.},
}
@article {pmid41160616,
year = {2025},
author = {Jia, S and Liu, Q and Liu, P and Zhao, W and Li, S},
title = {Association of perchlorate, nitrate, and thiocyanate with age-related macular degeneration in the United States.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0334919},
pmid = {41160616},
issn = {1932-6203},
mesh = {Humans ; *Nitrates/urine/adverse effects ; *Thiocyanates/urine/adverse effects ; Female ; Male ; United States/epidemiology ; Middle Aged ; *Macular Degeneration/epidemiology/chemically induced/urine ; Aged ; *Perchlorates/urine/adverse effects ; Adult ; Nutrition Surveys ; Risk Factors ; },
abstract = {Perchlorate, nitrate, and thiocyanate are endocrine-disrupting chemicals, but their associations with AMD is unclear. This study aims to investigate this relationship. We included 4727 participants aged 40 years and older from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) were applied to investigate the single, non-linear, and combined effects on AMD risk. Nitrate exposure was positively associated with any AMD risk (OR Any AMD, 1.19; 95% CI, 1.05-1.35; P = 0.010) and early AMD risk (OR Early AMD, 1.19; 95% CI, 1.05-1.36; P = 0.010); compared to the first quartile, the highest quartile of nitrate (OR, 1.94; 95% CI, 1.18-3.19; P = 0.012) and thiocyanate (OR, 1.70; 95% CI, 1.19-2.42; P = 0.006) levels were positively associated with AMD risk. The results of RCS showed a nonlinear relationship between nitrate exposure (P for nonlinearity = 0.020), thiocyanate (P for nonlinearity = 0.041), and AMD risk. WQS analysis indicated a positive relationship between mixed exposure and AMD risk (OR, 1.24; 95% CI, 1.01 to 1.51; P = 0.037). This study indicated that high urinary nitrate and thiocyanate levels were associated with an increased AMD risk among US adults. However, the cross-sectional design precludes causal inference.},
}
@article {pmid41159651,
year = {2025},
author = {Gorski, M and Grunin, M and Herold, JM and Fröhlich, B and Behr, M and Wheeler, N and Bush, WS and Song, YE and Zhu, X and Blanton, SH and Pericak-Vance, MA and Heid, IM and Haines, JL and , },
title = {Diverse-Ancestry GWAS of Age-Related Macular Degeneration on 16,108 Examined Cases and 18,038 Controls.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {13},
pages = {51},
pmid = {41159651},
issn = {1552-5783},
support = {R01 EY022310/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; Complement Factor H/genetics ; *Genetic Predisposition to Disease/ethnology ; *Genome-Wide Association Study ; *Macular Degeneration/ethnology/genetics ; *Polymorphism, Single Nucleotide ; *Population Groups/ethnology/genetics ; },
abstract = {PURPOSE: In 2016, the International Age-related Macular Degeneration Genomics Consortium analyzed data from approximately 50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD (adAMD) in individuals of European ancestry and did not include diverse ancestries, fine-mapping per ancestry, or a predictive model with/without the contributions of one lead genetic risk locus, CFH. Therefore, we analyzed full cross-ancestry IAMDGC data, utilizing the newest imputation panel, and identified genetic risk loci across and between ancestries contributing to AMD.<br><br>METHODS: In this IAMDGC 2.0 analysis, we included cross-ancestry data via custom exome chip imputed genome-wide via TOPMedv2, in 16,108 ophthalmologically confirmed adAMD cases and 18,038 examined AMD-free controls. We included both male and female subjects and four diverse ancestries. Data were analyzed from June 2021 to May 2024.<br><br>RESULTS: Utilizing diverse ancestry data (cases/controls&#xa0;=&#xa0;15,616/16,723 European, 50/357 African, 207/322 Asian, and 235/636 Other), we identified 28 loci at P&#xa0;<&#xa0;5 &#xd7; 10-8, including 2 additional AMD loci compared to IAMDGC 1.0 (SERPINA1 and CPN1). Fine-mapping supported one ancestry-shared signal around HTRA1/ARMS2 and nine signals around CFH without African ancestry contribution. The 52-variant genetic risk score with and the 44-variant score without CFH predicted adAMD in all ancestries (area under the curve [AUC] = 0.80/0.75, 0.65/0.64, and 0.80/0.79, respectively).<br><br>CONCLUSIONS: Our results indicate that the genetic underpinning of adAMD is mostly shared between ancestries. We also identify the CFH variant as being less relevant in specific ancestries, indicating a difference in pathogenic burden between ancestries. We increased the available genomic data for AMD over 300-fold with the IAMDGC 2.0 imputation, making it a valuable resource for further AMD genetic analysis.},
}
@article {pmid41158821,
year = {2025},
author = {Sanfelippo, WA and Oley, M and Harrelson, H and Vilar, N},
title = {Artery of Percheron infarct with multiple cranial nerve palsies and Horner Syndrome.},
journal = {American journal of ophthalmology case reports},
volume = {40},
number = {},
pages = {102458},
pmid = {41158821},
issn = {2451-9936},
abstract = {PURPOSE: To report a case of a rare stroke variant involving the artery of Percheron leading to ocular motility compromise.<br><br>OBSERVATIONS: A 65-year-old man presented to the neuro-ophthalmology clinic with multiple cranial nerve palsies and Horner Syndrome. He was three weeks post-thrombolytic therapy to treat an ischemic stroke, and his pertinent medical history consisted of hyperlipidemia and macular degeneration. On physical exam, the patient experienced bilateral vertical gaze paresis, incomplete left Horner syndrome, right-sided cranial nerve VI palsy, and partial left-sided cranial nerve VII palsy. Based on the infarction patterns demonstrated on MRI, the patient was diagnosed with an artery of Percheron infarct.<br><br>CONCLUSIONS AND IMPORTANCE: The artery of Percheron is a rare variant of posterior cerebral circulation that supplies both paramedian thalamic zones in addition to variably supplying the midbrain. Overall, this case highlights the importance of considering rare anatomical variants when working up ophthalmic deficits in a stroke patient. Early diagnosis can lead to adequate therapy and prevent complications in the future.},
}
@article {pmid41158184,
year = {2025},
author = {Kananen, F},
title = {Treatment results switching from aflibercept to bevacizumab in wet age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {18},
number = {11},
pages = {2116-2121},
pmid = {41158184},
issn = {2222-3959},
abstract = {AIM: To examine effects of switching intravitreal aflibercept to bevacizumab in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Data from patients treated for nAMD with anti-vascular endothelial growth factor (VEGF) injections at &#xd6;rebro University Hospital between January 2014 and June 2020, were extracted from the Swedish macular register (SMR). A total of 230 eyes were included in the study: 116 in the study/bevacizumab switch group and 114 in the control/aflibercept group. Central retinal thickness (CRT) was measured at baseline and after 2y. Primary outcome was mean change in best corrected visual acuity (BCVA) between baseline and 2y. Secondary outcome variables included proportion of patients with a clinically significant change in BCVA [increase or decrease of &#x2265;15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters], mean change in CRT, number of anti-VEGF injections, number of visits assessing disease activity and number of visits with active disease.<br><br>RESULTS: The mean difference in BCVA between baseline and 2y was 1.13&#xb1;14.47 ETDRS letters in the bevacizumab switch group and 1.81&#xb1;13.01 ETDRS letters in the aflibercept group. The lower bound of the 95% confidence interval of the difference in BCVA was -4.25, indicating non-inferiority within a 5 ETDRS letter limit. No significant differences in mean change of CRT between baseline and 2y were detected (study -185.9&#xb1;167.0 versus control -149.4&#xb1;193.1 &#xb5;m, P=0.127). The distribution of clinically significant improvement (P=0.598) or worsening (P=0.508) of BCVA during follow-up did not show statistically significant differences between groups. The number of anti-VEGF injections administered (study 12.76&#xb1;2.20 versus control 13.10&#xb1;4.20, P=0.442), the number of visits assessing disease activity (P=0.301), and the number of visits with active disease (P=0.065) did not show differences between subjects receiving bevacizumab and aflibercept treatment. No significant differences were detected in baseline characteristics between the study and control groups, including age, BCVA, CRT, neovascular membrane type or location, duration of symptoms or prior cataract surgery.<br><br>CONCLUSION: Switching to off-label bevacizumab in patients responding to initial aflibercept treatment is non-inferior to continued aflibercept treatment with respect to change in visual acuity at 2y. Switching anti-VEGF from aflibercept to bevacizumab may be a viable option in clinical settings with limited resources.},
}
@article {pmid41158183,
year = {2025},
author = {Ai, LQ and Zhu, LY and Yang, H and Ye, J},
title = {Critical role of lipid metabolism in axial myopia development.},
journal = {International journal of ophthalmology},
volume = {18},
number = {11},
pages = {2195-2204},
pmid = {41158183},
issn = {2222-3959},
abstract = {The global prevalence of myopia is becoming increasingly severe, with epidemiological models predicting that by 2050, approximately 50% of the world's population will be affected by myopia, and about 10% will suffer from high myopia. The incidence of high myopia is projected to increase fivefold, making it the leading cause of irreversible vision impairment. Myopia often leads to various complications and has been associated with other ocular diseases, including early-onset cataracts, age-related macular degeneration, and primary open angle glaucoma. As a result, the control and management of myopia have become ongoing and long-term research priorities. The pathogenesis of myopia involves complex multisystem interactions. Current mainstream theories focus primarily on choroidal hypoxia-induced scleral remodeling, with neurotransmitters such as acetylcholine and dopamine playing regulatory roles. However, recent studies have increasingly suggested that changes in nutritional intake, including proteins, fats, and cholesterol, may also be related to myopia development. The role of lipid metabolism in the onset and progression of myopia has gradually attracted growing attention. Therefore, this review aims to systematically elucidate the molecular mechanisms of lipid metabolism regulatory networks in axial myopia, integrating multidimensional factors to provide a theoretical foundation for precision intervention strategies.},
}
@article {pmid41158172,
year = {2025},
author = {Guo, YJ and Chen, ZQ and Zhao, J},
title = {Integrating plasma proteomics and genome-wide association data to identify therapeutic targets for retinal neurodegenerative diseases in Europeans.},
journal = {International journal of ophthalmology},
volume = {18},
number = {11},
pages = {2170-2182},
pmid = {41158172},
issn = {2222-3959},
abstract = {AIM: To employ proteome-wide Mendelian randomization (MR) to explore novel protein and drug targets for retinal neurodegenerative diseases (RND) in individuals of European ancestry.<br><br>METHODS: This study used summary data-based MR to analyze the correlation between plasma protein levels and three RND, with protein data derived from two independent large-scale proteomics datasets. Potential drug targets were identified using Bayesian colocalization, followed by MR analysis, sensitivity testing, and external validation. Drug prediction and molecular docking were conducted to evaluate the druggability of the target proteins.<br><br>RESULTS: The study identified six promising protein targets, each successfully replicated at least twice. The results included three proteins related to diabetic retinopathy (ICAM1, GCKR, WARS), two proteins related to age-related macular degeneration (WARS, BRD2), and two proteins related to glaucoma (SVEP1, NPTXR). Additionally, drug prediction and molecular docking indicated that five drugs (fenofibrate, trofinetide, ticagrelor, lifitegrast, acetaminophen) effectively bound to the target proteins.<br><br>CONCLUSION: This study identified six potential protein targets for RND and five existing drugs with therapeutic potential. By integrating plasma proteomics with genetic data, it provides a cost-effective framework for drug discovery.},
}
@article {pmid41157282,
year = {2025},
author = {Iliadis, I and Pechnikova, NA and Poimenidou, M and Almaliotis, DD and Tsinopoulos, I and Yaremenko, TV and Yaremenko, AV},
title = {Applications of Modern Cell Therapies: The Latest Data in Ophthalmology.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {10},
pages = {},
pmid = {41157282},
issn = {2075-1729},
abstract = {Cell-based therapeutics are redefining interventions for vision loss by enabling tissue replacement, regeneration, and neuroprotection. This review surveys contemporary cellular strategies in ophthalmology through the lenses of therapeutic effectiveness, translational readiness, and governance. We profile principal sources-embryonic and induced pluripotent stem cells, mesenchymal stromal cells, retinal pigment epithelium, retinal progenitor and limbal stem cells-and enabling platforms including extracellular vesicles, encapsulated cell technology and biomaterial scaffolds. We synthesize clinical evidence across age-related macular degeneration, inherited retinal dystrophies, and corneal injury/limbal stem-cell deficiency, and highlight emerging applications for glaucoma and diabetic retinopathy. Delivery routes (subretinal, intravitreal, anterior segment) and graft formats (single cells, sheets/patches, organoids) are compared using standardized structural and functional endpoints. Persistent barriers include GMP-compliant derivation and release testing; differentiation fidelity, maturation, and potency; genomic stability and tumorigenicity risk; graft survival, synaptic integration, and immune rejection despite ocular immune privilege; the scarcity of validated biomarkers and harmonized outcome measures and ethical, regulatory, and health-economic constraints. Promising trajectories span off-the-shelf allogeneic products, patient-specific iPSC-derived grafts, organoid and 3D-bioprinted tissues, gene-plus-cell combinations, and cell-free extracellular-vesicle therapeutics. Overall, cell-based therapies remain investigational. With adequately powered trials, methodological harmonization, long-term surveillance, scalable xeno-free manufacturing, and equitable access frameworks, they may eventually become standards of care; at present, approvals are limited to specific products/indications and regions, and no cell therapy is the standard of care for retinal disease.},
}
@article {pmid41157186,
year = {2025},
author = {Chujo, S and Chung, YC and Quarta, A and Kwak, H and Soylu, C and Abbasgholizadeh, R and Alhelaly, M and Rattu, R and Corradetti, G and Nittala, MG and Sadda, SR},
title = {Improving OCTA Visualization of Macular Neovascularization via a Grayscale Inversion Method.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {10},
pages = {},
pmid = {41157186},
issn = {2075-1729},
abstract = {BACKGROUND: Age-related macular degeneration is a major cause of vision loss, and improved visualization of macular neovascularization (MNV) on OCT angiography (OCTA) could enhance clinical assessment. This study aimed to establish a simple and accessible image enhancement method.<br><br>METHODS: We retrospectively analyzed 24 eyes from 22 patients with MNV at the Doheny UCLA Eye Centers. Grayscale-inverted OCTA images were generated using the basic "Invert" function in ImageJ 1.51 23. Each original and inverted image pair was assessed for seven MNV-related features: structure and area within 3 &#xd7; 3 mm, 6 &#xd7; 6 mm and 12 &#xd7; 12 mm scans, and presence of polypoidal lesions. Twenty-one ophthalmologists graded visibility using a standardized five-point scale. Paired comparisons were performed using the Wilcoxon signed-rank test.<br><br>RESULTS: Grayscale inversion significantly improved the visualization of MNV structure in 6 &#xd7; 6 mm scans (mean difference: +0.67 &#xb1; 1.02; p = 0.008), 12 &#xd7; 12 mm scans (+0.62 &#xb1; 1.07; p = 0.013), and detection of polypoidal lesions (+0.43 &#xb1; 0.98; p = 0.030). No significant differences were found for 3 &#xd7; 3 mm structure (p = 0.793) or area-related features (all p > 0.3).<br><br>CONCLUSIONS: Grayscale inversion may enhance MNV visibility and polypoidal lesion detection on OCTA. As this study relied solely on subjective assessments, future work should incorporate quantitative image analysis.},
}
@article {pmid41156523,
year = {2025},
author = {Pieńczykowska, K and Bryl, A and Mrugacz, M},
title = {The Impact of a High-Fat Diet on Eye Health.},
journal = {Nutrients},
volume = {17},
number = {20},
pages = {},
pmid = {41156523},
issn = {2072-6643},
mesh = {Humans ; *Diet, High-Fat/adverse effects ; Oxidative Stress ; Fatty Acids, Omega-3/administration &amp; dosage ; *Eye Diseases/etiology ; Lipid Metabolism ; Dietary Supplements ; Inflammation/etiology ; Retina/metabolism ; Animals ; *Eye ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Background: The increasing prevalence of high-fat diets is associated with a rise in metabolic and neurodegenerative diseases. The retina and retinal pigment epithelium are metabolically active tissues exposed to oxidative stress, making them particularly vulnerable to lipid excess. Materials and Methods: A systematic literature review was conducted covering years until 2025 inclusive. Results: High-fat diets lead to cholesterol accumulation and lipid metabolism disturbances in the retina, retinal pigment epithelium, and ocular vessels. They activate inflammatory and oxidative stress pathways, resulting in structural and functional damage. Omega-3 deficiency exacerbates inflammation, while supplementation improves the tear film stability, corneal epithelial function, intraocular pressure regulation, and exerts neuroprotective effects. Conclusions: High-fat diets represent a significant risk factor for ocular diseases by disrupting lipid metabolism, enhancing inflammation, and inducing oxidative stress. Omega-3 fatty acid supplementation reduces inflammation and supports ocular functions.},
}
@article {pmid41156216,
year = {2025},
author = {Kucharczuk, J and Kasprzak, H and Gawęcki, M},
title = {Switching from Aflibercept to Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration: Short-Term Results from Real-Life Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {20},
pages = {},
pmid = {41156216},
issn = {2077-0383},
abstract = {Purpose: To evaluate anatomical and functional outcomes after switching from aflibercept to faricimab in patients with neovascular age-related macular degeneration (nAMD) with suboptimal response. Methods: This retrospective study included 72 eyes of 66 patients with nAMD previously treated with intravitreal aflibercept using a treat-and-extend regimen. Indications for switching included persistent retinal fluid, pigment epithelial detachment (PED), lack of best-corrected visual acuity (BCVA) improvement, or inability to extend treatment intervals beyond four weeks. Patients received three monthly loading doses of faricimab followed by individualized 8- to 16-week dosing. Follow-up comprised six visits over a mean of 8.5 ± 1.4 months. Outcomes included BCVA (logMAR), retinal morphology (subretinal fluid-SRF; intraretinal fluid-IRF; pigment epithelial detachment-PED), central subfoveal thickness (CST), and treatment interval changes. Results: Switching to faricimab led to significant short-term anatomical improvement, primarily reduction in subretinal fluid (p < 0.0001), with maximal effect during the loading phase. Resolution of SRF was significant at the end of the follow up; however, IRF changes were transient and not sustained beyond three months. PED reduction reached borderline significance (p = 0.0455). CST decreased during the loading phase (p < 0.0001) but returned to baseline thereafter. BCVA improved only after loading (p = 0.0287) but not at final follow-up. Treatment intervals were extended by a mean of ~2 weeks (p < 0.0001), increasing in 80% of eyes. Eyes with fewer prior injections and better baseline BCVA achieved superior final visual outcomes. Conclusions: Switching to faricimab provides short-term anatomical benefits and treatment-interval extension without sustained visual gain. Functional improvements tended to be greater in patients with fewer injections and shorter treatment duration prior to switch.},
}
@article {pmid41156127,
year = {2025},
author = {Nishiyama, T and Hirai, H and Miyata, K and Nishi, T and Ueda, T and Kase, S},
title = {A Pilot Study on Structural Changes of Choroidal Vasculature Following Intravitreal Anti-VEGF Injection in Neovascular Age-Related Macular Degeneration: Faricimab vs Ranibizumab.},
journal = {Journal of clinical medicine},
volume = {14},
number = {20},
pages = {},
pmid = {41156127},
issn = {2077-0383},
abstract = {Objectives: This paper aims to explore optical coherence tomography (OCT)-based choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents, faricimab and ranibizumab, in a pilot study. Methods: This retrospective pilot cohort study enrolled 28 treatment-naïve nAMD patients who received three consecutive intravitreal anti-VEGF injections at Nara Medical University Hospital. In total, 17 patients (61%) were Type 1 MNV and 11 patients (39%) were Type 2 MNV. Patients were divided into a faricimab group (13 eyes) and a ranibizumab group (15 eyes). The type of macular neovascularization (MNV) and the presence of polyps were recorded. The central choroidal thickness (CCT) and the ratio of luminal area to choroidal area (L/C ratio), derived from binarized OCT images, were measured at baseline after the first and third injections. Results: Type 1 MNV was observed in 61% of eyes, with polyps confirmed in 53%. There was no significant difference in best corrected visual acuity (BCVA) for both faricimab and ranibizumab during treatment (p = 0.12, 0.94, respectively). After the third injection, a dry macula was achieved in 62% of the faricimab group and 60% of the ranibizumab group. In the ranibizumab group, CCT significantly decreased after the first injection, while no significant change was observed in the faricimab group. Conversely, the L/C ratio significantly decreased in the faricimab group after the third injection (p = 0.010). Among faricimab-treated eyes, those with type 1 MNV showed a significantly greater reduction in the L/C ratio compared to type 2 MNV (p = 0.017). Conclusions: This pilot study suggests that faricimab may exert combined anti-VEGF and Ang-2 effects predominantly on type 1 MNV, potentially leading to vascular constriction. These exploratory findings warrant confirmation in larger studies.},
}
@article {pmid41156023,
year = {2025},
author = {Yu, HS and Cho, H and Shin, YU and Hong, EH and Koh, SH},
title = {Protective Effect of Curcumin in Oxidative Stress-Induced Injury on Retinal Pigment Epithelial Cells.},
journal = {Journal of clinical medicine},
volume = {14},
number = {20},
pages = {},
pmid = {41156023},
issn = {2077-0383},
support = {2020R1A2C1010229//National Research Foundation of Korea/ ; 2021R1I1A1A01059690//National Research Foundation of Korea/ ; 202400000000843//Hanyang University/ ; },
abstract = {Background/Objectives: Oxidative stress is the major cause of retinal pigment epithelial cell death. We used oxidative stress-injured retinal pigment epithelial cells to investigate the protective effects of curcumin, a strong antioxidant, on the Nod-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: To evaluate the effect of curcumin, cell viability was measured with cell counting kit-8 and lactate dehydrogenase assays. Hydrogen peroxide (H2O2)-injured ARPE-19 cells were treated with different curcumin concentrations. We performed a wound healing assay and dichlorodihydrofluorescein diacetate staining. Western blotting and immunofluorescence staining were performed to evaluate the changes in inflammasome levels in the ARPE-19 cells. Result: H2O2 (300 μM) reduced the viability of ARPE-19 cells. However, treatment with 7.5 μM curcumin enhanced ARPE-19 cell viability and reduced cell toxicity. Curcumin also reduced reactive oxygen species (ROS) levels in the H2O2-induced damaged ARPE-19 cells and attenuated the H2O2-dependent levels of the NLRP3 inflammasome and its related signaling proteins. Conclusions: Curcumin demonstrated protective effects against oxidative stress in retinal pigment epithelial cells by attenuating the activation of the NLRP3 inflammasome pathway. These findings suggest the therapeutic potential of curcumin as an anti-inflammatory and antioxidant agent for macular degeneration.},
}
@article {pmid41155961,
year = {2025},
author = {Hassan, MSA and Zhong, C and Hassan, F and Li, SK},
title = {Targeting the Eye: RNA-Based Therapies, Interferences, and Delivery Strategies.},
journal = {Pharmaceutics},
volume = {17},
number = {10},
pages = {},
pmid = {41155961},
issn = {1999-4923},
support = {R01 EY031452/EY/NEI NIH HHS/United States ; R01EY031452/EY/NEI NIH HHS/United States ; },
abstract = {Recent advances in molecular biology have led to the development of RNA-based therapeutics, offering significant promise for treating various eye diseases. Current RNA therapeutics include RNA aptamers, antisense oligonucleotides (ASOs), small interfering RNA (siRNA), and messenger RNA (mRNA) that can target specific genetic and molecular pathways involved in eye disorders. In addition to their potential in therapy, RNA technologies have also provided tools for mechanistic studies to improve the understanding of eye diseases, expanding the possibilities of RNA-based treatments. Despite the utility of RNA in studying eye disease mechanisms and its potential in disease treatment, only a few RNA-based therapies have been approved for posterior eye diseases. This paper reviews RNA interference and related ocular delivery and posterior eye diseases, focusing on the use of RNA aptamers, siRNA, short hairpin RNA (shRNA), and microRNA (miRNA). Approaches using RNA to advance our understanding of eye diseases and disease treatments, particularly in the posterior segment of the eye, are discussed. It is concluded that RNA therapeutics offer a novel approach to treating a variety of eye diseases by targeting their molecular causes. siRNA, shRNA, miRNA, and ASO can directly silence disease-driving genes, while RNA aptamers bind to specific targets. Although many RNA-based therapies are still in experimental stages, they hold promise for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), glaucoma, and inherited retinal disorders. Effective delivery methods and long-term safety are key challenges that need to be addressed for these treatments to become widely available.},
}
@article {pmid41155120,
year = {2025},
author = {Patel, MJ and Sheth, S and Mar, J and Gregori, NZ and Sengillo, JD},
title = {Surgical Approaches to Retinal Gene Therapy: 2025 Update.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {10},
pages = {},
pmid = {41155120},
issn = {2306-5354},
abstract = {Gene therapy offers a promising new frontier in the treatment of inherited and acquired retinal disease. This review describes the current surgical delivery approaches for gene therapy to the retina-subretinal, suprachoroidal, and intravitreal-and provides an update on the state of the art for each method in 2025.},
}
@article {pmid41155071,
year = {2025},
author = {Barthelemy, N and Sridhar, J and Sengillo, JD},
title = {Gene Therapy for Wet Age-Related Macular Degeneration.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {10},
pages = {},
pmid = {41155071},
issn = {2306-5354},
abstract = {The prevalence of wet age-related macular degeneration (AMD) in the US is expected to increase to 82 million by 2050. Addressing the specialized needs for this population will become increasingly challenging as prevalence rises. Frequent anti-vascular endothelial growth factor (anti-VEGF) injections have been the recourse for this population; however, the burden wet AMD places on patients underscores the critical need for durable therapeutic approaches. Gene therapy is a bioengineered treatment that has transformed the management of previously untreatable disorders. Ongoing advancements and refinements in its biomechanism could lead to more sustainable treatment options for wet AMD. In this article, we provide recent updates on gene therapy trials for wet AMD.},
}
@article {pmid41154560,
year = {2025},
author = {Mimura, T and Noma, H},
title = {Title Oxidative Stress in Age-Related Macular Degeneration: From Molecular Mechanisms to Emerging Therapeutic Targets.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
pmid = {41154560},
issn = {2076-3921},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the elderly, and oxidative stress, primarily mediated by reactive oxygen species (ROS), is widely recognized as a central driver of its onset and progression. The retina is highly susceptible to oxidative damage due to its elevated oxygen consumption, abundant polyunsaturated fatty acids, and continuous exposure to light. Recent studies have elucidated molecular mechanisms in which mitochondrial dysfunction, disruption of redox homeostasis, inflammation, and complement activation interact to promote degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. In addition to age-related oxidative stress, environmental factors such as motor vehicle exhaust and volatile organic compounds (VOCs) can accelerate the accumulation of lipofuscin and drusen, thereby fostering a chronic pro-inflammatory milieu. From a therapeutic perspective, beyond conventional antioxidant supplementation, emerging strategies targeting oxidative stress-related pathways have gained attention, including mitochondrial protectants, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, anti-inflammatory agents, and gene therapy. Importantly, several innovative approaches are under investigation, such as saffron supplementation with neuroprotective properties, drug repositioning of levodopa, and nanotechnology-based delivery systems to enhance retinal bioavailability of antioxidants and gene therapies. This review summarizes the pathophysiological role of oxidative stress in AMD from a molecular mechanistic perspective and discusses recent advances in research and novel therapeutic targets.},
}
@article {pmid41153316,
year = {2025},
author = {Romero-Oraá, R and Herrero-Tudela, M and López, MI and Hornero, R and Romero-Aroca, P and García, M},
title = {An Ensemble Model for Fundus Images to Aid in Age-Related Macular Degeneration Grading.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {20},
pages = {},
pmid = {41153316},
issn = {2075-4418},
support = {TED2021-131913B-I00//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; PID2023-148895OB-I00//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; TED2021-131913B-I00//European Regional Development Fund/ ; PID2023-148895OB-I00//European Regional Development Fund/ ; Instituto de Salud Carlos III//Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine/ ; PIF-UVa//Universidad de Valladolid/ ; },
abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly population. Periodic examinations through fundus image analysis are paramount for early diagnosis and adequate treatment. Automatic artificial intelligence algorithms have proven useful for AMD grading, with the ensemble strategies recently gaining special attention. Methods: This study presents an ensemble model that combines 2 individual models of a different nature. The first model was based on the ResNetRS architecture and supervised learning. The second model, known as RETFound, was based on a visual transformer architecture and self-supervised learning. Results: Our experiments were conducted using 149,819 fundus images from the Age-Related Eye Disease Study (AREDS) public dataset. An additional private dataset of 1679 images was used to validate our approach. The results on AREDS achieved a quadratic weighted kappa of 0.7364 and an accuracy of 66.03%, which outperforms the previous methods in the literature. Conclusions: The ensemble strategy presented in this study could be useful for the screening of AMD in a clinical setting. Consequently, eye care for AMD patients would be improved while clinical costs and workload would be reduced.},
}
@article {pmid41153266,
year = {2025},
author = {Perkins, SW and Shah, N and Whitney, J and Matar, K and Yu, HJ and Wykoff, CC and Ehlers, JP},
title = {Radiomic Characterization and Automated Classification of Drusen Substructure Phenotype Associated with High-Risk Dry Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {20},
pages = {},
pmid = {41153266},
issn = {2075-4418},
support = {T32 EY024236/EY/NEI NIH HHS/United States ; T32EY024236/NH/NIH HHS/United States ; },
abstract = {Background/Objectives: Optical coherence tomography (OCT)-reflective drusen substructures (ODSs) are associated with the conversion of intermediate AMD to geographic atrophy (GA). However, ODSs must be manually identified, a laborious process introducing bias and variation. This study proposes objective radiomic metrics of drusen phenotypes and validates them for the prediction of GA development and GA growth rate. Methods: A total of 104 drusen with high-reflective cores (H-type), 105 with low-reflective cores (L-type), 129 conical drusen (C-type), and 101 normal drusen (N-type) were segmented from OCT images. Radiomic features were extracted from these drusen, and the most important features for drusen classification were extracted from the retinal pigment epithelium-Bruch's membrane compartment of 743 OCT scans of eyes with dry AMD and used to predict GA conversion and fast growth. Results: Radiomic features classified drusen phenotypes with AUC = 0.87-0.95. H-type drusen have a higher reflectivity, greater variation in reflectivity, and coarser texture (p < 0.001). L-type drusen have a lower reflectivity and greater variation in reflectivity (p < 0.0001). C-type drusen have a less spherical shape and more disordered internal reflectivity (p < 0.001). N-type drusen have a more spherical shape and more uniform internal reflectivity (p < 0.001). These radiomic features predict the conversion from intermediate AMD to GA and top-quartile GA growth rate with AUC = 0.59-0.74 at years 1-3. Conclusions: These results demonstrate the potential of clinical phenotype-grounded radiomics for objective automated drusen analysis, GA risk stratification, and clinical prediction.},
}
@article {pmid41153254,
year = {2025},
author = {Al-Khersan, H and Sodhi, SK and Cao, JA and Saju, SM and Pattathil, N and Zhou, AW and Choudhry, N and Russakoff, DB and Oakley, JD and Boyer, D and Wykoff, CC},
title = {Deep Learning-Based Segmentation of Geographic Atrophy: A Multi-Center, Multi-Device Validation in a Real-World Clinical Cohort.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {20},
pages = {},
pmid = {41153254},
issn = {2075-4418},
abstract = {Background: To report a deep learning-based algorithm for automated segmentation of geographic atrophy (GA) among patients with age-related macular degeneration (AMD). Methods: Validation of a deep learning algorithm was performed using optical coherence tomography (OCT) images from patients in routine clinical care diagnosed with GA, with and without concurrent nAMD. For model construction, a 3D U-Net architecture was used with the output modified to generate a 2D mask. Accuracy of the model was assessed relative to the manual labeling of GA with the Dice similarity coefficient (DSC) and correlation r[2] scores. Results: The OCT data set included 367 scans from the Spectralis (Heidelberg, Germany) from 55 eyes in 33 subjects; 267 (73%) scans had concurrent nAMD. In parallel, 348 scans were collected using the Cirrus (Zeiss), from 348 eyes in 326 subjects; 101 (29%) scans had concurrent nAMD. For Spectralis data, the mean DSC score was 0.83 and r[2] was 0.91. For Cirrus data, the mean DSC score was 0.82 and r[2] was 0.88. Conclusions: The reported deep learning algorithm demonstrated strong agreement with manual grading of GA secondary to AMD on the OCT data set from routine clinical practice. The model performed well across two OCT devices as well as amongst patients with GA with concurrent nAMD, suggesting applicability in the clinical space.},
}
@article {pmid41152160,
year = {2025},
author = {Chen, M and Yang, W and Xu, S and Lu, Y and Yang, Z and Li, F and Gu, Z},
title = {[Research on attention-enhanced networks for subtype classification of age-related macular degeneration in optical coherence tomography].},
journal = {Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi},
volume = {42},
number = {5},
pages = {901-909},
pmid = {41152160},
issn = {1001-5515},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/classification/diagnostic imaging ; *Neural Networks, Computer ; },
abstract = {Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.},
}
@article {pmid41151537,
year = {2025},
author = {Lee, JK and Lee, J and Park, JB and Kim, K and Yu, SY},
title = {Topographic Progression of Geographic Atrophy and Visual Acuity in Non-Exudative Age-related Macular Degeneration.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2025.0103},
pmid = {41151537},
issn = {2092-9382},
abstract = {PURPOSE: To investigate long-term topographic progression of the geographic atrophy (GA) area based on location and analyze its correlation with visual acuity in patient with GA secondary to non-neovascular AMD in Korean patient cohort.<br><br>METHODS: Medical records and imaging data of 58 eyes from 34 patients with GA were retrospectively reviewed using fundus autofluorescence (FAF). Regions of interest were defined as concentric ring-shaped zones with diameters of 1, 2, 3, and 4 mm centered on the fovea (Zones 0-3), each subdivided into superior, temporal, inferior, and nasal sectors. The foveal center was determined using optical coherence tomography (OCT), and sectoral GA areas were measured on FAF with the semi-automated software (Region Finder 2.6.2.0). Correlations among GA area enlargement, GA growth rate, and changes in best-corrected visual acuity (BCVA) were evaluated.<br><br>RESULTS: The mean GA area enlarged from 4.10 to 16.57 mm2 and mean BCVA decreased from 0.34 to 1.06 logarithm of the minimal angle of resolution (logMAR) at 5 years of follow-up. The mean overall GA area growth rate was 1.96 mm2/year. During yearly follow-up from baseline to 5 years, there was significant differences in GA growth rate of Zone 3 inferior (P < .005). The GA area changes of Zone 3 inferior was significantly correlated with BCVA. In subgroup with BCVA decreased under 1.0 logMAR during follow-up, there was a higher growth rate in Zone 2 nasal sector, 2 to 3 years before.<br><br>CONCLUSION: The overall GA growth rate was 1.96 mm2/year in the 5-year follow-up of our Korean cohort. Changes in the GA growth rate in the nasal perifoveal region (Zone 2) may be associated with subsequent clinically meaningful visual decline.},
}
@article {pmid41149849,
year = {2025},
author = {Bennie, J and Ramsey, DJ},
title = {Navigating the Decision to Discontinue Intravitreal Injection Therapy in End-Stage Neovascular Age-Related Macular Degeneration.},
journal = {Journal of personalized medicine},
volume = {15},
number = {10},
pages = {},
pmid = {41149849},
issn = {2075-4426},
abstract = {Introduction: The management of neovascular age-related macular degeneration (nAMD) is constrained by diminishing therapeutic options for retina specialists and their patients when the disease reaches its end stages. Methods: Clinical insights emerge from two case narratives in which patients benefitted from discontinuation of anti-VEGF therapy. Results: Long-term management of nAMD with intravitreal injections of agents targeting vascular endothelial growth factor (VEGF) is crucial for slowing progression of the disease and is generally well-tolerated. However, vision often declines as the disease progresses over time, even with treatment. This article presents strategies for aligning therapeutic goals with their expected visual outcome when an eye has reached end-stage disease. It addresses considerations for how and when to stop treatment when vision becomes limited, taking into consideration the visual status of the fellow eye and incorporating input from low vision specialists who can better assess best-corrected visual acuity (BCVA) and optimize the visual function of patients. We also acknowledge the potential benefits of switching either the dose or the agent that targets VEGF to alter the long-term visual outcome of treatment. Finally, we discuss the importance of taking into consideration related manifestations of the disease, such as macular scarring, geographic atrophy, or other retinal or optic nerve diseases which may limit vision and thus the utility of continued nAMD treatment. Conclusions: Building a strong patient-physician relationship is essential for navigating the shared decision-making process of when to stop treatment for nAMD.},
}
@article {pmid41149584,
year = {2025},
author = {Fang, Y and Zheng, H and Chen, Y and Ryu, B and Qian, ZJ},
title = {A Sulfated Polysaccharide from Gelidium crinale Suppresses Oxidative Stress and Epithelial-Mesenchymal Transition in Cultured Retinal Pigment Epithelial Cells.},
journal = {Marine drugs},
volume = {23},
number = {10},
pages = {},
pmid = {41149584},
issn = {1660-3397},
mesh = {*Epithelial-Mesenchymal Transition/drug effects ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; Humans ; *Polysaccharides/pharmacology/isolation &amp; purification/chemistry ; Hydrogen Peroxide/pharmacology ; Cell Line ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; Macular Degeneration/drug therapy ; *Rhodophyta/chemistry ; Signal Transduction/drug effects ; NF-kappa B/metabolism ; Epithelial Cells/drug effects/metabolism ; Sulfates/pharmacology/chemistry ; Edible Seaweeds ; },
abstract = {Age-related macular degeneration (AMD) progresses to vision-threatening dry and wet forms, with no effective dry AMD treatments available. The sulfated polysaccharide (GNP, 25.8 kDa) derived from Gelidium crinale exhibits diverse biological activities and represents a potential source of novel therapeutic agents. This study employed a hydrogen peroxide (H2O2)-induced oxidative stress and epithelial-mesenchymal transition (EMT) model in retinal pigment epithelial (RPE) cells to investigate GNP's protective mechanisms against both oxidative damage and EMT. The results demonstrated that GNP effectively suppressed oxidative stress, with the 600 μg/mL dose significantly inhibiting excessive reactive oxygen species (ROS) generation to levels comparable to untreated controls. Concurrently, at concentrations of 200-600 μg/mL, GNP inhibited NF-κB signaling and increased the Bax/Bcl-2 ratio, effectively counteracting H2O2-induced oxidative damage and cell apoptosis. Furthermore, in H2O2-treated ARPE-19 cells, 600 μg/mL GNP significantly reduced the secretion of N-cadherin (N-cad), Vimentin (Vim), and α-smooth muscle actin (α-SMA), while increasing E-cadherin (E-cad) expression, consequently inhibiting cell migration. Mechanistically, GNP activated the Nrf2/HO-1 pathway, thereby mitigating oxidative stress. These findings suggest that GNP may serve as a potential therapeutic agent for dry AMD.},
}
@article {pmid41148250,
year = {2025},
author = {Terao, R and Kitamoto, K and Aoki, S and Totani, K and Sugiyama, S and Yamanari, M and Inoue, T and Azuma, K and Obata, R},
title = {Short-term changes in retinal pigment epithelium after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration evaluated by polarization-sensitive optical coherence tomography.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41148250},
issn = {1435-702X},
abstract = {PURPOSE: To characterize changes in retinal pigment epithelium (RPE) melanin distribution after anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study enrolled treatment-na&#xef;ve nAMD eyes with macular neovascularization (MNV) type 1 and type 2. Eyes were treated with intravitreal faricimab injection every four weeks. Visual acuity and anatomical changes were assessed with multimodal imaging. Polarization-sensitive OCT (PS-OCT) was used to examine the polarimetric entropy, quantitative indicator of melanin distribution, at the RPE segment. Retinal sensitivity was assessed with microperimetry.<br><br>RESULTS: Twelve patients with MNV type 1 and seven eyes with MNV type 2 were included. Faricimab significantly improved visual acuity and central subfield thickness (p&#x2009;=&#x2009;0.0064,&#x2009;<&#x2009;0.0001, respectively). In MNV type 1, faricimab significantly increased mean entropy in the overall Early Treatment Diabetic Retinopathy Study (ETDRS) grid area (p&#x2009;=&#x2009;0.0386). In the per-grid analysis, entropy of type 1 also significantly increased, whereas type 2 showed significant reduction (p&#x2009;=&#x2009;0.0071, 0.0389, respectively). As MNV type 2 regresses, high-entropy area corresponding to MNV decreased and low-entropy area surrounding them increased (p&#x2009;=&#x2009;0.019, 0.0058, respectively), suggesting RPE migration onto MNV. RPE entropy was significantly associated with visual acuity or retinal sensitivity after the treatment (p&#x2009;=&#x2009;0.00475, 0.0307, respectively).<br><br>CONCLUSIONS: After anti-VEGF treatment for type 1 or type 2 MNV, RPE melanin distribution at the MNV and the surrounding area distinctly changed. They were associated with visual function. The present study supported deterioration of visual function in eyes with type 2 MNV after anti-VEGF treatment resulted not only from subretinal scar formation but RPE atrophy surrounding the MNV.},
}
@article {pmid41147841,
year = {2025},
author = {Gallagher, D and Hurley, D and O'Brien, L and Petronzi, V and Connell, P and Dooley, I},
title = {VISUAL AND ANATOMICAL OUTCOMES AFTER VITRECTOMY WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR INJECTION IN PATIENTS WITH SUBMACULAR HEMORRHAGES SECONDARY TO WET AGE-RELATED MACULAR DEGENERATION.},
journal = {Retinal cases &amp; brief reports},
volume = {19},
number = {6},
pages = {744-748},
doi = {10.1097/ICB.0000000000001660},
pmid = {41147841},
issn = {1937-1578},
mesh = {Humans ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Vitrectomy/methods ; *Retinal Hemorrhage/etiology/therapy/diagnosis ; Male ; Female ; *Fibrinolytic Agents/administration &amp; dosage ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/complications/diagnosis ; Aged, 80 and over ; Tomography, Optical Coherence ; Retrospective Studies ; Injections, Intraocular ; Treatment Outcome ; Middle Aged ; },
abstract = {PURPOSE: Submacular hemorrhages (SMHs) are most commonly associated with wet age-related macular degeneration and their size and duration are strong prognostic factors for visual outcome. The aim of this audit was to evaluate outcomes of direct injection of submacular tissue plasminogen activator into these lesions during pars plana vitrectomy.<br><br>METHODS: All patients presenting to the Mater Misericordiae Hospital from January 2017 to December 2019 with large submacular hemorrhages secondary to wet age-related macular degeneration who underwent this treatment were included for review. All 10 patients underwent complete pars plana vitrectomy, injection of 0.2 mL (50 &#x3bc;g) of subretinal tissue plasminogen activator, and air tamponade. Preoperative and postoperative evaluations included VA testing, optical coherence tomography, and slit lamp examination.<br><br>RESULTS: Eight patients (80%) showed improvement of their VA, with four patients achieving a VA of &#x2264;0.4 LogMAR (20/50). Six patients had a total clearing of the macular hemorrhage, with a further two patients having subtotal clearance. One patient subsequently developed a retinal detachment requiring oil tamponade.<br><br>CONCLUSION: Submacular hemorrhage secondary to wet age-related macular degeneration is a sight threatening event with a varied prognosis, but in most cases, vitrectomy with subretinal tissue plasminogen activator injection results in improved anatomical and visual outcomes.},
}
@article {pmid41147690,
year = {2025},
author = {Wang, M and Gao, FJ and Tang, W and Lei, B and Hu, F and Ma, J and Sadda, SR and Kannan, R and Sreekumar, PG and Xu, G},
title = {Deficiency of 2-Oxoglutarate Carrier (Slc25a11) Drives RPE Epithelial-to-Mesenchymal Transition and Exacerbates Subretinal Fibrosis in Neovascular Age-Related Macular Degeneration.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70271},
doi = {10.1111/acel.70271},
pmid = {41147690},
issn = {1474-9726},
support = {R01EY30141/EY/NEI NIH HHS/United States ; //Keck Foundation/ ; 82101150//National Natural Science Foundation of China/ ; 82101124//National Natural Science Foundation of China/ ; },
abstract = {Subretinal fibrosis significantly contributes to vision loss in neovascular age-related macular degeneration (nAMD). Epithelial-to-mesenchymal transition (EMT) in RPE cells is a key early step in subretinal fibrosis. While mitochondrial dysfunction in RPE is involved, the metabolic and molecular connections between EMT and mitochondria are not well understood. This study explores the role of oxoglutarate carrier (OGC; Slc25a11) on EMT and investigates the molecular mechanisms, focusing on its role in mitochondrial metabolism and GSH transport. OGC-silenced or overexpressed ARPE-19 cells were treated with TGF-β2 (10 ng/mL) for 48 h. EMT markers, cell migration, mtGSH, and mitochondrial bioenergetics and signaling pathways were assessed. In vivo, subretinal fibrosis was induced in wild-type and OGC[+/-] mice via laser photocoagulation. Fibrosis volume was measured using optical coherence tomography and immunostaining in RPE-choroid flat mounts. OGC silencing aggravated EMT, while overexpression attenuated TGF-β2-induced EMT, cell proliferation, and migration. OGC knockdown significantly enhanced RPE EMT, as evidenced by upregulated expression of α-SMA, fibronectin, collagen type I, and Slug, while E-cadherin was downregulated. OGC overexpression improved mitochondrial bioenergetics, whereas its inhibition reduced mitochondrial respiration, which was further aggravated by co-treatment with TGF-β2. Loss of OGC promoted cell proliferation and migration through Slug-mediated EMT. OGC depletion stimulated EMT via pSmad2/3 upregulation, dependent on the PI3K/AKT signaling pathway activation. In vivo studies further demonstrate that subretinal fibrosis was significantly augmented in OGC[+/-] mice via TGF-β2-dependent PI3K signaling. In conclusion, modulating OGC expression in RPE affects EMT and mitochondrial function, making OGC a potential therapeutic target for subretinal fibrosis in nAMD.},
}
@article {pmid41146803,
year = {2025},
author = {Kominami, T and Ota, J and Takeuchi, J and Yuki, K and Ushida, H},
title = {Extensive Macular Atrophy With Pseudodrusen Complicated by Macular Neovascularization in a Japanese Patient: A Case Report.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e93258},
pmid = {41146803},
issn = {2168-8184},
abstract = {Recognizing the characteristic vertically oriented atrophy, pseudodrusen distribution, and retinal pigment epithelium-Bruch's membrane separation is critical for distinguishing extensive macular atrophy with a pseudodrusen-like appearance (EMAP) from age-related macular degeneration (AMD). Early identification of neovascular complications and prompt anti-vascular endothelial growth factor therapy can stabilize macular neovascularization (MNV) and help preserve residual vision in this rare retinal disorder. To the best of our knowledge, this is the first reported case of EMAP with MNV in an Asian patient. This report aims to describe the clinical presentation, imaging features, genetic findings, and therapeutic response in a Japanese woman with EMAP complicated by MNV, which is rarely reported in Asia. A 63-year-old woman presented with decades-long nyctalopia and progressive visual loss. Fundus examination and fundus autofluorescence showed vertically oriented macular atrophy, widespread pseudodrusen, and peripheral paving-stone degeneration. Optical coherence tomography (OCT) demonstrated diffuse separation of the retinal pigment epithelium from Bruch's membrane. These findings lead to the diagnosis of EMAP. Fluorescein angiography, indocyanine green angiography, and OCT angiography revealed type 1 MNV in the left eye. Whole-exome sequencing detected no pathogenic variants associated with inherited retinal disease or AMD. The neovascular lesion was treated with intravitreal aflibercept on a treat-and-extend regimen; after seven injections, the MNV became inactive.},
}
@article {pmid41146323,
year = {2025},
author = {Lee, Y and Rahman, S and Tao, BK and Fang, T and Akil, H and Ferrara, D and Lam, S and Navajas, EV},
title = {Recognition and treatment of polypoidal choroidal vasculopathy and age-related macular degeneration in British Columbia.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {118},
pmid = {41146323},
issn = {2056-9920},
abstract = {OBJECTIVE: To assess ethnic differences in the prevalence, diagnosis, and management of polypoidal choroidal vasculopathy (PCV) compared to typical neovascular age-related macular degeneration (nAMD) among Chinese and Caucasian patients in British Columbia.<br><br>METHODS: A retrospective chart review was conducted between 2008 and 2013 based on predefined inclusion criteria. Demographic, diagnostic, and clinical outcome data&#x2014;including race, lesion type, diagnostic modality, and treatment response&#x2014;were extracted and analyzed using RStudio.<br><br>RESULTS: Of the 416 eyes reviewed, 92.07% (383/416, N&#x2009;=&#x2009;Total sample number) were from Caucasian patients and 7.93% (33/416, N&#x2009;=&#x2009;Total sample number) from Chinese patients. No statistically significant difference in median age at diagnosis was observed between ethnic groups. ICGA was used in 3.57% (2/56, N&#x2009;=&#x2009;Total number of PCV cases) of PCV cases. Anti-VEGF monotherapy was the predominant treatment modality, while combination therapy with photodynamic therapy (PDT) was employed in 5.38% (22/353&#x2009;+&#x2009;56) of cases. There were no significant differences in visual acuity (VA) gains or central retinal thickness (CRT) reductions between PCV and nAMD diagnoses, nor between ethnic groups. Under anti-VEGF monotherapy, visual acuity and central retinal thickness outcomes were similar between PCV and nAMD and across the ethnic groups evaluated, within the limitations of the study design.<br><br>CONCLUSION: PCV, though less common than typical nAMD, was identified in both Chinese and Caucasian patients, with a trend toward younger age at presentation compared to nAMD. The low utilization of ICGA may contribute to the underdiagnosis of PCV. Nevertheless, anti-VEGF monotherapy yielded comparable outcomes across diagnoses and ethnicities, underscoring the importance of equitable diagnostic and therapeutic strategies in nAMD care.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-025-00744-8.},
}
@article {pmid41144243,
year = {2025},
author = {Perilli, R and Mastropasqua, R and Mastropasqua, L},
title = {Turning diabetic retinopathy telescreening into a multi-telescreening.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251389641},
doi = {10.1177/11206721251389641},
pmid = {41144243},
issn = {1724-6016},
}
@article {pmid41143474,
year = {2025},
author = {Habibi, A and Ashrafkhorasani, M and Emamverdi, M and Chinasigari, PR and Goerdt, L and Gao, L and McGwin, G and Clark, ME and Abbasgholizadeh, R and Fasih-Ahmad, S and Vatanatham, C and Wang, ZC and Mishra, Z and Nittala, MG and Owsley, C and Curcio, CA and Hu, ZJ and Sadda, SR},
title = {Total Retinal Pigment Epithelium Thickness and Reflectivity, in Relation to Histology and Vision, at the Aging-AMD Transition: ALSTAR2 Baseline.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {13},
pages = {42},
pmid = {41143474},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; Female ; Aged ; Male ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Visual Acuity/physiology ; *Aging/physiology ; *Macular Degeneration/physiopathology/pathology/diagnosis ; Aged, 80 and over ; Middle Aged ; Dark Adaptation/physiology ; },
abstract = {PURPOSE: The retinal pigment epithelium (RPE) is critical in age-related macular degeneration (AMD) pathophysiology. We compare total RPE thickness (TRPET) and normalized reflectivity intensity (TNRR) on optical coherence tomography (OCT) among healthy aged and early AMD (eAMD) and intermediate AMD (iAMD) eyes, and to visual function.<br><br>METHODS: Spectralis OCT volume scans from aged, eAMD, and iAMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step) of the Alabama Study on Early Age-related Macular Degeneration 2 (ALSTAR2) baseline sample were automatically segmented for vitreous, nerve fiber layer (NFL), and total RPE (measured up to the centerline of the interdigitation zone) and manually corrected. TNRR was normalized with reference to vitreous and NFL within zones of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Vision tests included rod-mediated dark adaptation (RMDA), a functional benchmark for AMD risk (reported as rod intercept time [RIT]), and other tests of rod- and cone-mediated function.<br><br>RESULTS: Of 502 eyes of 502 participants (71.8 &#xb1; 6.1 years, 59.6% female participants), 252 were healthy, 147 had eAMD, and 103 had iAMD. TRPET was significantly thinner in iAMD compared with eAMD and healthy eyes (P < 0.001) and moderately correlated with longer RIT in all eyes (r = 0.12-0.35). TNRR was lower in iAMD eyes compared to eAMD and healthy eyes (P < 0.01); correlation with RIT was weaker but significant.<br><br>CONCLUSIONS: Reduced TRPET and TNRR in AMD and their correlation with RMDA are statistically significant due to the large sample. Whether they have practical utility for AMD detection will be learned from ongoing longitudinal studies. In ALSTAR2, non-RPE layers may contribute to delayed RMDA.},
}
@article {pmid41143143,
year = {2025},
author = {Biswas, RK and Sheth, JU and Shrivastava, V and Kaur, J and Sinha, S and Pal, SS and Nandi, K and Das, S},
title = {Faricimab for Refractory Neovascular Age-Related Macular Degeneration: Retrospective Real-World Evidence from India.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3881-3887},
pmid = {41143143},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the anatomical and functional outcomes of faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) in a real-world Indian cohort over a six-month period.<br><br>PATIENTS AND METHODS: In this retrospective, multicenter study, 24 eyes with refractory nAMD were switched to faricimab on a pro-re-nata regimen between January 2024 and December 2024. Patients underwent monthly evaluation for three months, then per physician discretion, with measurement of best-corrected visual acuity (BCVA), central foveal thickness (CFT), and proportions of eyes with intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED).<br><br>RESULTS: The cohort's mean age was 68.1 (&#xb1;10.6) years, and prior to switching had received an average of 11.4 (&#xb1;9.1) anti-VEGF injections. During the six-month period, eyes underwent a mean of 2.63 (&#xb1; 1.34) faricimab injections (range, 1-5): 25.0% received one injection, 29.2% two, 16.7% three, 16.7% four, and 12.5% five. Mean BCVA improved from 0.66 (&#xb1;0.4) logMAR at baseline to 0.47 (&#xb1;0.34) at month 1, 0.35 (&#xb1;0.32) at month 2, and 0.27 (&#xb1;0.27) at months 3 and 6 (P&#x2264;0.0003). Mean CFT decreased from 471.1 (&#xb1;246.4) &#xb5;m to 337.3 (&#xb1;198.3) &#xb5;m (month 1), 265.1 (&#xb1;90.7) &#xb5;m (month 2), 217.7 (&#xb1;41.3) &#xb5;m (month 3), and 209.4 (&#xb1;36.0) &#xb5;m (month 6) (P<0.0001). SRF resolved in 90.9% of affected eyes (P<0.001), IRF in 87.5% (P=0.0006), and PED in 54.5% (P=0.32), with complete fluid resolution in 83.3% of eyes (P=0.00002). No ocular or systemic adverse events occurred.<br><br>CONCLUSION: In this real-world Indian cohort of refractory nAMD, faricimab delivered robust visual gains, significant CFT reduction, and high rates of fluid resolution, with over half of eyes requiring &#x2264;2 injections over six months, supporting its role as an effective switch therapy. Further prospective studies are warranted to optimize dosing intervals and long-term outcomes.},
}
@article {pmid41141822,
year = {2025},
author = {Wang, T and Zhang, Y and Xiao, W and Jin, Y and Yi, Q and Chen, Q and Xiang, J and Wang, R and Li, J and Liu, L},
title = {Tetrahedral DNA Framework Penetrating Ocular Barrier for Treatment of Retinal Oxidative Stress.},
journal = {ACS omega},
volume = {10},
number = {41},
pages = {48984-48990},
pmid = {41141822},
issn = {2470-1343},
abstract = {Excessive accumulation of reactive oxygen species in the retina is the predominant pathogenic mechanism underlying dry age-related macular degeneration (dAMD). Although antioxidant chemicals have been shown to be effective in reducing ROS levels, their bioavailability and therapeutic efficacy are restricted by ocular barriers. Herein, we developed a tetrahedral framework nucleic acid (tFNA)-based antioxidant drug for the treatment of retinal oxidative stress diseases. By exploiting their penetration capability, these tFNAs penetrated multiple ocular tissues and cellular barriers. These tFNAs protected retinal pigment epithelium cells from glyoxal-induced oxidative stress damage by exerting their intrinsic antioxidant properties through the JNK and AKT pathways upon entering the cells. The subconjunctival administration of tFNAs alleviated structural damage and reduced retinal cell apoptosis in a retinal oxidative stress rat model. These results indicated that tFNAs are a promising therapeutic drug for the treatment of retinal oxidative stress diseases, which sheds light on the development of dAMD therapy.},
}
@article {pmid41140907,
year = {2026},
author = {Nagai, N and Shinoda, H and Matsubara, H and Terasaki, H and Hirano, T and Kato, A and Miki, A and Hirai, H and Murao, F and Imaizumi, H and Gomi, F and Mitamura, Y and Ogata, N and Kusuhara, S and Yasukawa, T and Murata, T and Sakamoto, T and Kondo, M and Ozawa, Y},
title = {Associations between Progression of Retinal Pigment Epithelial and Outer Retinal Atrophy and Choroidal Thickness: A 2-Year observation.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100939},
pmid = {41140907},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the clinical course of retinal pigment epithelial and outer retinal atrophy (RORA) with best-corrected visual acuity (BCVA) and risk factors for rapid progression to explore the pathogenesis.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Data on eyes with fovea-involved RORA associated with age-related macular degeneration were collected over time from 10 hospitals in Japan.<br><br>METHODS: Data on ophthalmic examination, BCVA, and OCT images were analyzed.<br><br>MAIN OUTCOME MEASURES: Relationships between changes in BCVA and extents of RORA and outer plexiform layer (OPL) deterioration and their associations with central choroidal thickness (CCT) and pachychoroid characteristics at baseline were evaluated.<br><br>RESULTS: Of the 53 eyes of 53 patients (mean age; 74.9 &#xb1; 1.4 years), 32 eyes (60.4%) belonged to men. The progression in the mean extent of OPL deterioration was evident at year 1, whereas that of RORA, BCVA impairment, thinning of the central retinal thickness, and CCT became apparent at year 2 (P < 0.05). Changes in the extents of RORA and OPL deterioration and BCVA were correlated (P < 0.05). Baseline CCT negatively correlated with baseline RORA and the changes in extent of RORA (P < 0.05). After adjusting for age and sex, a longer extent of RORA at baseline predicted BCVA worsening &#x2265;0.04 per year (odds ratio [OR], 3.444; 95% confidence interval [CI], 1.015-11.691; P = 0.047). Greater horizontal extension of RORA &#x2265;175 &#x3bc;m/y was frequently observed in eyes with thinner CCT <180 &#x3bc;m (OR, 4.684; 95% CI, 1.288-17.036; P = 0.019), subretinal drusenoid deposits (SDDs) (OR, 6.714; 95% CI, 1.555-28.988; P = 0.011), and drusen (OR, 4.392; 95% CI, 1.176-16.410; P = 0.028) and less observed in eyes with pachychoroid characteristics (OR, 0.038; 95% CI, 0.003-0.454, P = 0.010) at baseline after adjusting for age and baseline extent of RORA; similar risks for greater vertical extension of RORA were observed.<br><br>CONCLUSIONS: The change in BCVA paralleled the changes in the extents of RORA and OPL deterioration. Rapid BCVA impairment was observed in eyes with longer RORA at baseline. A thinner choroid, SDD, and drusen were risk factors, and pachychoroid characteristics were protective factors against RORA progression. Further studies are warranted to better understand the progression of RORA and vision loss.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41140906,
year = {2026},
author = {Goldberg, EA and Ross, CJ and Douglas, VP and Ivanov, A and Elze, T and Miller, JW and Lorch, AC and , },
title = {Data Duplication and Errors in Large Medical Data Sets: A Case Study in the IRIS® Registry.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100933},
pmid = {41140906},
issn = {2666-9145},
abstract = {PURPOSE: To investigate entry errors and data duplication within the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) utilizing cataract surgery (CS), neodymium-doped: yttrium aluminum garnet (YAG) capsulotomy, age-related macular degeneration (AMD), and diabetic retinopathy (DR) records.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients in the IRIS Registry.<br><br>METHODS: We collected records of CS and YAG capsulotomy with specified laterality within the IRIS Registry (years 2013-2023), identifying eyes having >1 record and eyes having &#x2265;1 record on a date after the first entry (different date duplication, D d). Additionally, we identified eyes amongst records of DR and AMD with (1) a diagnosis indicating a more severe stage then reversion to the less severe stage or (2) a transition to a more severe stage before later being diagnosed with the less severe stage, defined as transition errors. We investigated potential predictors of D d and transition errors among patient and practice characteristics by evaluating the permutation feature importance (PFI) of classification models.<br><br>MAIN OUTCOME MEASURES: For CS and YAG capsulotomy, we measure the proportion of eyes having >1 procedure record, having >1 record only on the initial procedure date, and having &#x2265;1 procedure record on a date after the first entry. For DR and AMD, we measure the proportion of eyes reverting to an earlier stage after starting at a later stage and the proportion reverting to an earlier stage after transitioning to a later stage.<br><br>RESULTS: Of the 14 718 896 CS-treated eyes, 30.9% had duplicates, with 5.5% having D d . For YAG capsulotomy, out of 5 113 679 eyes, 29.1% had duplicates, with 4.1% having D d . For AMD and DR, 13.6% and 12.7% of eyes, respectively, exhibited transition errors. Models captured a relationship between the eye's first practice on record and the data errors under study, indicated by F1-loss = 0.230 (D d model), 0.062 (transition error model) on average by PFI.<br><br>CONCLUSIONS: Data duplication in large medical data sets necessitates caution when analyzing repeated procedures or relapsing conditions. Addressing problematic errors requires transparency and communication amongst stakeholders across organizations. Within the IRIS Registry, the results indicated an association between the first record's originating practice and data errors, providing an investigative entry point for upstream data stewards.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41140896,
year = {2026},
author = {Dadgar, N and Fung, K and McClintic, S and Metea, C and Llorenç, V and Saleh, M and Nakamura, YK and Jahrig, C and Kiang, L and Janowitz, C and Davin, S and Balter, A and Le Cao, KA and Karstens, L and Martin, TM and Klein, ML and Lin, P},
title = {Age-related Eye Disease Studies Supplements and Genetic Risk Score Are Crucial Determinants of Intestinal Microbial Alterations in Advanced Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100920},
pmid = {41140896},
issn = {2666-9145},
abstract = {OBJECTIVE: Determine whether an intestinal microbial signature is associated with advanced age-related macular degeneration (AMD); investigate the relationship between the microbiota and AMD genetic risk, intestinal immunoglobulin-A (IgA), and Age-Related Eye Disease Studies (AREDS) supplementation.<br><br>DESIGN: Case-control study.<br><br>METHODS: Fecal 16S rRNA sequencing, DESeq2 differential abundance, and IgA-sequencing.<br><br>SUBJECTS: Advanced AMD and age-similar non-AMD control subjects.<br><br>MAIN OUTCOME MEASURES: Differential abundance plots using DESeq2, &#x3b1; and &#x3b2; diversity, and impact of AREDS supplementation and genetic risk on AMD microbiota.<br><br>RESULTS: In 85 advanced AMD compared with 49 healthy control subjects' intestinal microbiota, exploratory partial least-squares-discriminant analysis (PLS-DA) showed that gut microbiome composition was able to predict AMD with moderate confidence (cross validation error rates, 0.28-0.36) with the potential for overfitting. A higher AMD genetic risk score was associated with lower gut microbial diversity (P = 0.0086; Spearman r = -0.3), a finding confirmed by multiple linear regression with confounding covariates, whereas AREDS supplementation was associated with increased gut bacterial diversity (coefficient, 2.64; P < 0.05). Differential abundance plots showed increased Proteobacteria and many differentially abundant genera (including Prevotella, Desulfovibrio, Oscillospira, and Ruminococcaceae) in AMD versus controls. Flow cytometry and IgA-sequencing suggested increased IgA-coating of gut bacteria in the age-related maculopathy susceptibility 2 (ARMS2) gene risk genotype, including higher IgA indices for Prevotella. These findings are hypothesis-generating and require functional validation. Predicted metabolic pathways (via piphillin) that differed between AMD and controls included lipid metabolism and xenobiotic processing by cytochrome P450; these findings are inferred and require confirmation by metabolomic studies.<br><br>CONCLUSIONS: The intestinal microbiome is able to predict advanced AMD via PLS-DA. AREDS supplementation and genetic risk are crucial determinants of the AMD microbiome, which interacts with gut immunity by increasing IgA binding to certain bacteria. Understanding how the gut microbiome and its metabolites interact with gut immunity and host genetics will allow us to further investigate the microbiome to find potentially novel therapeutic targets in AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41140895,
year = {2026},
author = {Xu, Z and Lin, R and Wang, X and Liu, Y and Huang, C and Wang, C and Bao, Z},
title = {Association of Physical Frailty and Genetic Predisposition with Risk of Irreversible Eye Diseases.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100910},
pmid = {41140895},
issn = {2666-9145},
abstract = {OBJECTIVE: The evidence linking frailty to overall and specific irreversible eye diseases is limited. Moreover, it is unclear whether frailty is associated with similar increased risk across individuals with different genetic risk profiles. The aim of this study was to examine the association between frailty and overall and specific irreversible eye diseases and explore the modification effect of genetic risk of glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in such associations.<br><br>DESIGN: Prospective cohort study.<br><br>PARTICIPANTS: The study included a total of 409 579 White participants in the UK Biobank study.<br><br>METHODS: Physical frailty was defined by 5 components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. Participants were classified as nonfrail, prefrail, or frail. Polygenic risk score was categorized as low (tertile 1), intermediate (tertile 2), or high (tertile 3). Cox regression was used to assess the association of physical frailty with irreversible eye diseases.<br><br>MAIN OUTCOMES AND MEASURES: Irreversible eye diseases were identified using hospital admission electronic health records and death registries.<br><br>RESULTS: Among 409 579 individuals (mean age, 56.5 years; 46.5% male) with a median follow-up of 13.1 years, 10 927, 7 095, and 919 were diagnosed with irreversible eye disease in the nonfrail, prefrail, and frail groups, respectively. Prefrail and frail individuals showed increased risks of overall irreversible eye diseases, with a 12% higher risk for prefrail individuals (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.09-1.16) and a 47% higher risk for frail individuals (HR, 1.47; 95% CI, 1.37-1.58). Increased risks were also observed for specific irreversible eye diseases, including glaucoma (HR, 1.11 [95% CI, 1.06-1.17] for prefrailty; HR, 1.43 [95% CI, 1.28-1.61] for frailty), diabetic retinopathy (HR, 1.12 [95% CI, 1.03-1.21] for prefrailty; HR, 1.53 [95% CI, 1.34-1.73] for frailty), and AMD (HR, 1.13 [95% CI, 1.08-1.19] for prefrailty; HR, 1.35 [95% CI, 1.20-1.52] for frailty). Furthermore, individuals with more severe frailty status and higher genetic risk exhibited higher risks of irreversible eye diseases than those with low genetic risk and nonfrailty.<br><br>CONCLUSIONS: Frailty was associated with an increased risk of irreversible eye diseases, particularly among individuals with higher genetic risk. These findings suggest that targeted strategies to prevent and manage frailty may contribute to reducing the risk of irreversible eye diseases.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid41140340,
year = {2025},
author = {Christensen, CA and Gupta, N and Breazzano, MP},
title = {Novel Bilateral Geographic Atrophy Phenotype Associated With CRX Mutation.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251386364},
pmid = {41140340},
issn = {2474-1272},
abstract = {Purpose: To describe an atypical phenotype of retinal dystrophy in the setting of a heterozygous missense mutation (CRX-RD). Methods: The case is a 71-year-old woman previously diagnosed with advanced, non-neovascular, nonexudative age-related macular degeneration (AMD) who presented with longstanding blurry vision for consideration of intravitreal anti-complement factor therapy. Results: Ophthalmic examination showed geographic atrophy (GA) in both eyes, without evidence of drusen or drusenoid deposits. Genetic panel testing revealed a pathogenic, heterozygous missense mutation in CRX, the NM_000554.6(CRX) variant c.128G>A (p.Arg43His) (RCV001228802.6). Although CRX-RD is known to have phenotypic heterogeneity, cases with macular atrophy most commonly display bullseye maculopathy or benign concentric annular macular dystrophy. Conclusions: This case presenting with bilateral GA is consistent with a novel phenotype associated with a pathogenic variant of CRX and is an atypical presentation of RD simulating AMD.},
}
@article {pmid41140136,
year = {2025},
author = {Erbezci, M and Özen Tunay, Z and Öztürk, T},
title = {Preferred Retinal Locus in Juvenile Macular Dystrophy.},
journal = {Turkish journal of ophthalmology},
volume = {55},
number = {5},
pages = {239-244},
pmid = {41140136},
issn = {2149-8709},
mesh = {Humans ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Adolescent ; Young Adult ; Adult ; Child ; *Macular Degeneration/physiopathology/diagnosis ; *Fovea Centralis/pathology ; Fluorescein Angiography/methods ; Follow-Up Studies ; Ophthalmoscopy ; },
abstract = {OBJECTIVES: To evaluate foveal lesion and preferred retinal locus (PRL) locations and their effects on visual acuity in juvenile macular dystrophy (JMD) patients.<br><br>MATERIALS AND METHODS: In this retrospective study, 14 JMD patients (28 eyes) with bilateral central vision loss were examined using scanning laser ophthalmoscope/optical coherence tomography. Best-corrected visual acuity (BCVA), dimensions and location of the macular lesion, PRL location, and PRL stability were evaluated.<br><br>RESULTS: Mean BCVA was 0.84&#xb1;0.17 logarithm of the minimum angle of resolution. PRL was superiorly located in 64.3% of eyes and nasally located in 35.7%. PRL location was significantly associated with patient age (r=0.541, p=0.002); nasally located PRLs were more common in younger patients (mean age 15.1&#xb1;2.8 years) while superiorly located PRLs were more common in older patients (mean age 22.4&#xb1;6.9 years). Superiorly located PRLs were significantly closer to the fovea than nasally located PRLs (p=0.014). Visual acuity worsened as lesion size increased and PRL-fovea distance increased. PRL-fovea distance was longer in younger patients and positively correlated with lesion dimensions and PRL-lesion distance.<br><br>CONCLUSION: In JMD patients, PRLs are predominantly located superiorly or nasally. In younger patients, PRLs are typically located nasally and farther from the fovea, with poorer visual acuity compared to older patients. Cortical adaptation mechanisms may play a role in changing PRL location with age. Understanding PRL characteristics in JMD is crucial for developing effective low-vision rehabilitation strategies.},
}
@article {pmid41139156,
year = {2025},
author = {Habot-Wilner, Z and Ostrovsky, M and Zur, D and Schwartz, S and Hagin, D and Gadoth, A and Ben-Ami, R and Paran, Y and Goldshmidt, H and Slutzkin, M and Adler, A and Levytskyi, K},
title = {Metagenomic next-generation sequencing: a game-changer in the diagnosis of unique intraocular infections.},
journal = {Eye (London, England)},
volume = {39},
number = {18},
pages = {3365-3371},
pmid = {41139156},
issn = {1476-5454},
mesh = {Humans ; Male ; Adult ; *High-Throughput Nucleotide Sequencing/methods ; Retrospective Studies ; *Metagenomics/methods ; Female ; Aged, 80 and over ; *Endophthalmitis/diagnosis/microbiology ; *Eye Infections, Bacterial/diagnosis/microbiology ; },
abstract = {OBJECTIVE: To thoroughly describe unique intraocular infections diagnosed by metagenomic next-generation sequencing (mNGS).<br><br>METHODS: A retrospective case series of patients presenting with challenging atypical intraocular infections at Tel Aviv Sourasky Medical Center during 2024. Clinical and demographic data, as well as mNGS results were extracted from patient records. mNGS was performed on the Illumina NextSeq500 platform using a custom bioinformatics pipeline. The following parameters were examined: Reads Per Million, Reads Per Million-ratio to negative control and E-index (K-mers*coverage/reads).<br><br>RESULTS: The study included three patients with novel presentations of intraocular infections, manifesting with atypical clinical manifestations and negative routine diagnostic workups. mNGS allowed the identification of Cytomegalovirus in a 43-year-old male with a history of autosomal dominant hyper-IgE syndrome, Bartonella henselae infection manifesting with photoreceptoritis, retinal vasculitis and global retinal dysfunction in a healthy 28-year-old female, and polymicrobial endophthalmitis with Rothia mucilaginosa and Pantoea agglomerans following intravitreal faricimab injection for neovascular age-related macular degeneration in an 81-year-old male. Treatment regimens were adjusted based on mNGS results.<br><br>CONCLUSIONS: Metagenomic next-generation sequencing has an important role in the diagnosis of challenging intraocular infections. It enables comprehensive pathogen identification and enhances the precision of treatment strategies.},
}
@article {pmid41138285,
year = {2025},
author = {Demiot, C and De Sousa, C and Labrunie, A and Danigo, A and Authier, D and Delavaud, JM and Robert, PY and Rocher, M},
title = {Descriptive analysis of the knowledge amongst French patients about neovascular age-related macular degeneration as a function of social vulnerability, health literacy and date of diagnosis.},
journal = {Journal francais d'ophtalmologie},
volume = {48},
number = {9},
pages = {104666},
doi = {10.1016/j.jfo.2025.104666},
pmid = {41138285},
issn = {1773-0597},
mesh = {Humans ; *Health Literacy/statistics &amp; numerical data ; Female ; Male ; *Health Knowledge, Attitudes, Practice ; Aged ; France/epidemiology ; Aged, 80 and over ; *Macular Degeneration/diagnosis/epidemiology/psychology ; Patient Education as Topic ; *Vulnerable Populations/statistics &amp; numerical data/psychology ; Surveys and Questionnaires ; *Wet Macular Degeneration/diagnosis/epidemiology/psychology ; Time Factors ; Socioeconomic Factors ; Risk Factors ; Quality of Life ; },
abstract = {Patient education (PE) programs for patients with neovascular age-related macular degeneration (nAMD) are essential to reduce the disease's impact on quality of life. To establish a PE program for nAMD, a descriptive quantitative study was conducted to (i) describe the population and their knowledge concerning nAMD, (ii) classify patients according to their knowledge of disease, and (iii) their social vulnerability, health literacy and the duration since diagnosis. Socio-demographic data of 100 nAMD patients (70 women and 30 men, 80±7 years of age) were collected and compared with data on their social vulnerability (simplified EPICES score) and health knowledge (health literacy questionnaire). Patients were classified into three groups according to their knowledge, evaluated with questionnaires including the themes of pathology, information retrieval, treatment, risk factors and self-monitoring. A subgroup analysis of these knowledge profiles was assessed according to social vulnerability, health literacy and duration since diagnosis. False beliefs and lack of knowledge about nAMD were noted in almost 50% of patients. Only 15 patients were familiar with the Amsler grid. Three groups of patients were identified according to their knowledge of disease. No link was found between knowledge levels and health literacy. Patients who did not understand their disease were the most vulnerable, searched for less information, and had the most recent diagnosis. There is a significant need to improve the knowledge of nAMD patients. Social vulnerability, duration since diagnosis and heterogeneity in patient knowledge must be considered when establishing a PE program.},
}
@article {pmid41138048,
year = {2025},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Can Gene Therapy Transform the Treatment Landscape of Posterior Segment Eye Diseases? A Comprehensive Review of Recent Advancements.},
journal = {Drugs},
volume = {85},
number = {12},
pages = {1585-1608},
pmid = {41138048},
issn = {1179-1950},
mesh = {Humans ; *Genetic Therapy/methods ; Animals ; Macular Degeneration/therapy/genetics ; *Eye Diseases/therapy/genetics ; Gene Editing ; *Retinal Diseases/therapy/genetics ; Gene Transfer Techniques ; Genetic Vectors ; *Posterior Eye Segment/pathology ; },
abstract = {Posterior segment eye diseases (PSEDs) encompass a diverse group of conditions affecting the retina, choroid, optic nerve, and vitreous humor, often leading to progressive and irreversible vision loss. Age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and inherited retinal diseases (IRDs) are among the most clinically significant PSEDs with a substantial global burden and economic impact. Conventional treatments for PSEDs have limitations that necessitate the development of novel therapies that address the underlying molecular drivers of the disease. Gene therapy has emerged as a promising approach, offering the potential for durable and curative outcomes through precise genetic manipulation. Advancements in gene therapy strategies, including gene augmentation, gene editing, RNA-based therapies, and optogenetics, have led to significant progress in preclinical studies and clinical trials across various PSED subtypes. US Food and Drug Administration (FDA) approval of voretigene neparvovec (Luxturna[®]) for RPE65-associated IRDs validated the clinical viability of ocular gene therapy, while ongoing trials for AMD, DR, and other IRDs continue to expand the therapeutic landscape. Innovations in viral and non-viral delivery systems, such as dual AAV vectors, lipid nanoparticles, and novel biomaterials, have enhanced the efficiency and specificity of gene delivery to the retina. However, challenges persist, including immune responses to viral vectors, limited transduction efficiency in certain cell types, and anatomical barriers posed by the blood-retinal barrier. Future directions in ocular gene therapy include the development of precision genome editing techniques, such as prime editing, miRNA-based regulation, and combinatorial approaches integrating gene therapy with stem cell transplantation or neuroprotective agents. As the field continues to evolve, addressing these challenges and optimizing gene therapy strategies will be crucial in translating the transformative potential of ocular gene therapy into clinical reality for patients with PSEDs.},
}
@article {pmid41136910,
year = {2025},
author = {Cho, Y and Yoo, WS and Kim, SJ and Chung, I},
title = {Characteristics of patients lost to follow-up after intravitreal anti-vascular endothelial growth factor therapy for exudative age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {598},
pmid = {41136910},
issn = {1471-2415},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Visual Acuity ; *Lost to Follow-Up ; Follow-Up Studies ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: This study aimed to analyze and compare the characteristics of patients with exudative age-related macular degeneration who were lost to follow-up after receiving intravitreal anti-vascular endothelial growth factor(anti-VEGF) injections versus those who maintained regular follow-up.<br><br>METHODS: This retrospective study included patients who were lost to follow-up for more than 1 year (n&#x2009;=&#x2009;79) or maintained follow-up (n&#x2009;=&#x2009;186) after treatment with intravitreal injections of ranibizumab or aflibercept for exudative age-related macular degeneration. Age, sex, place of residence, type of health insurance, distance from the hospital, laterality of involvement, and follow-up duration were analyzed.<br><br>RESULTS: There were no significant differences between the two groups in terms of age, sex, or type of health insurance. However, patients lost to follow-up resided significantly further from the hospital versus those with regular follow-up (33.1&#x2009;&#xb1;&#x2009;26.8 vs. 21.6&#x2009;&#xb1;&#x2009;8.5&#xa0;km; P&#x2009;=&#x2009;0.001). A significantly higher proportion of patients that were lost to follow-up had unilateral involvement (P&#x2009;<&#x2009;0.001) and resided in rural areas (P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Distance from the hospital, rural residency, and unilateral involvement are significantly associated with nonadherence to follow-up among patients with exudative age-related macular degeneration receiving intravitreal anti-VEGF injections.},
}
@article {pmid41136844,
year = {2025},
author = {Wang, L and Wang, YK and Li, D and Ma, J and Sun, Y and Li, X and Wang, H and Niu, S and Stacey, GN and Zhao, T and Hu, B and Zhou, Q and Wang, L and Hao, J},
title = {The Programme for Manufacture of hPSC‑Based Products for AMD and PD.},
journal = {Advances in experimental medicine and biology},
volume = {1486},
number = {},
pages = {227-236},
pmid = {41136844},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/therapy/pathology ; *Parkinson Disease/therapy/pathology ; *Pluripotent Stem Cells/cytology/transplantation ; Retinal Pigment Epithelium/cytology/pathology ; Cell Differentiation ; Animals ; Dopaminergic Neurons/transplantation/pathology ; *Stem Cell Transplantation/methods ; Regenerative Medicine/methods ; },
abstract = {Pluripotent stem cells (hPSCs) possess the unique ability to self-renew and differentiate into various functional cell types, positioning them as key "seed cells" in regenerative medicine. The development of PSC-based therapies offers new hope for treating complex diseases, and degenerative diseases, particularly those caused by the loss of specific cellular functions, such as macular degeneration, Parkinson's disease, spinal cord injury, diabetes, and cartilage damage. Cell replacement therapies using hPSC-committed cells can help halt disease progression or potentially cure these conditions. The Retinal Pigment Epithelium (RPE) is crucial for visual function and photoreceptor support, with its dysfunction implicated in age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Parkinson's disease (PD), a rapidly progressing neurodegenerative disorder marked by the loss of midbrain dopaminergic neurons (mDA), remains one of the most difficult neurological conditions to treat. Traditional therapies for these diseases have largely been ineffective. RPE and mDA neurons differentiated from hPSCs offer promising solutions for treating AMD and PD, their treatment methods are both cell replacement therapy, and they are the products used in the first batch of stem cell clinical research registration projects in China, so we will put these two products together. This chapter summarizes the differentiation and quality control strategies for hESC-derived RPE and mDA neurons as examples of the potential hPSC-derived cell therapies, under development at the Chinese Academy of Sciences and Beijing Institute for Stem Cell and Regenerative Medicine, for these complex, treatment-resistant diseases.},
}
@article {pmid41136840,
year = {2025},
author = {Jha, S and Hua, F and Dejene, R and Sarkar, S and Sharma, R and Bharti, K},
title = {Development of a Manufacturing Process for Clinical Autologous hiPSC-Derived Retinal Pigment Epithelium.},
journal = {Advances in experimental medicine and biology},
volume = {1486},
number = {},
pages = {165-178},
pmid = {41136840},
issn = {0065-2598},
mesh = {Humans ; Cell Differentiation ; *Induced Pluripotent Stem Cells/cytology/transplantation ; *Macular Degeneration/therapy/pathology ; *Retinal Pigment Epithelium/cytology/transplantation ; Tissue Engineering/methods ; Transplantation, Autologous ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. The disease progresses through early, intermediate, and advanced stages, with late forms including dry AMD (geographic atrophy) and wet AMD (choroidal neovascularization). Currently, there is no cure for dry AMD, which results from retinal pigment epithelium (RPE) cell loss. Induced pluripotent stem cell (iPSC)-based transplants offer a potential therapy by replacing atrophied RPE. This chapter outlines the manufacturing process, key parameters, and challenges of developing iPSC-derived RPE therapy. We engineered a clinical-grade iPSC-RPE patch using autologous cells from AMD patients. Starting from the patient blood, CD34+ cells were isolated, expanded, and reprogrammed using episomal plasmids. Twelve iPSC clones were generated, quality-tested, and three were selected for differentiation into mature RPE on a biodegradable scaffold. The final patch underwent QC assays for donor identity, sterility, and phenotype confirmation before transplantation. This work has led to a Phase I/IIa clinical trial to evaluate the safety and feasibility of auto-iPSC-RPE patches in AMD patients.},
}
@article {pmid41135684,
year = {2025},
author = {Saadane, A and von Lintig, J},
title = {The retinol-binding protein receptor STRA6 and melanin cooperatively sustain retinoid signaling and outer blood-retinal barrier integrity.},
journal = {The Journal of biological chemistry},
volume = {301},
number = {12},
pages = {110846},
pmid = {41135684},
issn = {1083-351X},
abstract = {Disruption of the outer blood-retinal barrier (oBRB) is a central feature of retinal degenerative diseases, including age-related macular degeneration, yet the molecular mechanisms maintaining this barrier in the adult eye remain poorly defined. STRA6, a high-affinity receptor for retinol-binding protein (RBP4), mediates vitamin A uptake at the basolateral membrane of the retinal pigment epithelium (RPE), while melanin protects ocular retinoid stores from photooxidative stress. We previously showed that STRA6 deficiency leads to downregulation of junctional proteins in the RPE. Here, we demonstrate that STRA6 and melanin act synergistically to preserve the integrity of the oBRB. In albino Stra6 knockout mice, ocular retinoid levels were severely reduced despite normal circulating retinol levels, and dietary vitamin A delivered via chylomicrons failed to compensate for the loss of RBP4-mediated transport. This led to a functional impairment of both rod- and cone-mediated responses, even under vitamin A-sufficient conditions. Mice also showed downregulated tight junction proteins (ZO-1, Claudin-1, Claudin-3), RPE disorganization, barrier leakage, and immune cell infiltration into the subretinal space. These defects were further exacerbated under dietary vitamin A restriction. Importantly, systemic treatment with the pan-retinoic acid receptor (RAR) agonist TTNPB restored junctional gene expression and oBRB function in Stra6[-/-] mice, providing evidence that barrier failure arises from impaired retinoid signaling rather than structural loss of STRA6 and melanin. These findings define a novel role for retinoic acid in sustaining RPE barrier function and highlight the combined importance of STRA6-mediated transport and melanin-dependent photoprotection in retinal homeostasis.},
}
@article {pmid41135050,
year = {2025},
author = {Pinhas, A and Pinhas, B and Dmitruk, E and Pinhas, S},
title = {Eye and Systemic Disease Management Changes After Teleophthalmology Screening in Primary Care: Retrospective Cross-Sectional Pilot Study of 200 Consecutive Patients.},
journal = {JMIR formative research},
volume = {9},
number = {},
pages = {e81918},
pmid = {41135050},
issn = {2561-326X},
mesh = {Humans ; Cross-Sectional Studies ; Pilot Projects ; Retrospective Studies ; Female ; Male ; Middle Aged ; *Primary Health Care ; Aged ; Adult ; Telemedicine ; *Eye Diseases/diagnosis/therapy ; Aged, 80 and over ; Adolescent ; Young Adult ; Child ; Disease Management ; *Mass Screening/methods ; Diabetic Retinopathy/diagnosis ; Ophthalmology/methods ; },
abstract = {BACKGROUND: Undiagnosed ocular diseases and ocular complications from systemic diseases are common in primary care populations, and many can be detected through retinal imaging before symptoms develop. Asynchronous store-and-forward teleophthalmology offers a scalable way to integrate eye screening into primary care, yet its broader impact beyond diabetes and diabetic retinopathy detection remains underexplored.<br><br>OBJECTIVE: This study evaluated the outcomes of asynchronous store-and-forward teleophthalmology screening in a primary care clinic, including detection and triage of ocular conditions and subsequent changes in eye and systemic management.<br><br>METHODS: This was a retrospective cross-sectional analysis of the first 200 patients screened in a single primary care clinic in Elmhurst, New York, between January and May 2025. Each patient underwent nonmydriatic external and posterior eye imaging, which was reviewed by a remote reading eye clinician. Reports included eye findings, triage decisions (routine monitoring vs in-person referral), and management recommendations. Subsequent changes in care were extracted from primary care and in-person specialist consult notes.<br><br>RESULTS: Of 200 patients (mean age 62.1, SD 19.0, range 11-100 years), 71.5% (143/200, 95% CI 64.9-77.3) had positive eye findings, and 40% (80/200, 95% CI 33.5-46.9) were referred for in-person eye examinations. Only 8.8% (7/80, 95% CI 4.3-17.0) of referrals were for diabetic retinopathy; most were for glaucoma suspects, age-related macular degeneration, cataracts, and other eye diseases. Image quality was high, with 98.2% (390/397, 95% CI 96.4-99.1) of fundus images being at least partially adequate. Of the 32 patients with documented in-person eye follow-up, 87.5% (28/32) of evaluations confirmed the screening findings. Eye management changes were initiated in 11 patients, whereas systemic management changes occurred in 70 patients, including new prescriptions for Age-Related Eye Disease Study 2 supplements, antihypertensives, diabetes medications, and lipid-lowering agents.<br><br>CONCLUSIONS: Asynchronous teleophthalmology screening in a primary care setting effectively identified both ocular diseases and ocular complications from systemic diseases, leading to meaningful changes in eye and systemic management. The low rate of diabetic retinopathy among referrals highlights the broader diagnostic value of retinal imaging beyond diabetes management. This care model offers a scalable, high-yield strategy for proactive disease detection and interdisciplinary intervention at the primary care level.},
}
@article {pmid41134689,
year = {2025},
author = {Xue, Q and Huang, J and Wang, B and Ji, J and Wang, L and Kumari, S and Lan, C and Xiao, M},
title = {FTO Fuels Aβ1-40-Induced Retinal Pigment Epithelium Cell Injury Associated With Pyroptosis by Erasing m6A Methylation of the lncRNA Neat1.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {20},
pages = {e71166},
doi = {10.1096/fj.202500272RRRR},
pmid = {41134689},
issn = {1530-6860},
support = {82101139//MOST | National Natural Science Foundation of China (NSFC)/ ; 2021J01750//| Natural Science Foundation of Fujian Province (Fujian Natural Science Foundation)/ ; 2023J01690//| Natural Science Foundation of Fujian Province (Fujian Natural Science Foundation)/ ; 2023GGA019//| Fujian Provincial Health Technology Project (Provincial Health Technology Project of Fujian Province)/ ; 2022QNA015//| Fujian Provincial Health Technology Project (Provincial Health Technology Project of Fujian Province)/ ; 2024Y9260//Fujian Provincial Department of Science and Technology ()/ ; },
mesh = {*RNA, Long Noncoding/metabolism/genetics ; *Pyroptosis ; *Retinal Pigment Epithelium/metabolism/pathology ; Humans ; Animals ; *Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/genetics ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Methylation ; *Adenosine/analogs &amp; derivatives/metabolism ; Macular Degeneration/metabolism/pathology/genetics ; Inflammasomes/metabolism ; Epigenesis, Genetic ; Mice, Inbred C57BL ; },
abstract = {Retinal pigment epithelium (RPE) degeneration in association with inflammation is a key feature of age-related macular degeneration (AMD) pathology. Amyloid β (Aβ) in drusenoid deposits, the hallmark of AMD, is a critical initiating component that causes RPE cell damage through the activation of the NLR family pyrin domain containing 3 (NLRP3)-mediated inflammatory response. Epigenetic mechanisms have been reported to contribute to the pathogenesis of AMD. However, the extent to which epigenetic modifications regulate Aβ-mediated RPE inflammatory damage and cell death remains unclear. N6-methyladenosine (m6A) is the most abundant RNA epigenetic regulation in eukaryotes. Herein, based on bioinformatics analysis, we identified that fat mass and obesity-associated protein (FTO) acts as an essential epigenetic regulator in Aβ1-40-mediated RPE inflammatory cell death. Activation of NLRP3 inflammasome-related RPE pyroptosis was evident through enhanced NLRP3, gasdermin D immunoreactivity, increased caspase-1 cleavage, elevated IL-1β secretion, and higher LDH activity. Deletion of FTO resulted in the inhibition of RPE pyroptosis in vitro and in vivo. Mechanistically, methylated RNA immunoprecipitation (MeRIP) combined with RNA-seq demonstrated that long noncoding RNA (lncRNA) Neat1 served as a downstream target of FTO, with FTO knockdown suppressing Neat1 expression in an m6A-dependent manner. Neat1 depletion deactivated inflammatory factors, thereby hindering Aβ1-40-induced RPE pyroptosis. Furthermore, FTO silencing attenuated Neat1-mediated pyroptosis, resulting in compromised retinal structure and function. These findings suggest that the FTO-Neat1-NLRP3 network provides potential targets to treat AMD while expanding our understanding of the role of epigenetically modified lncRNAs in Aβ-driven RPE injury.},
}
@article {pmid41132628,
year = {2025},
author = {Ou, S and Shi, F and Cai, M and Wu, Y},
title = {Conbercept Treatment for Heart-Shaped Vascular Intertwined Nets in Macular Neovascularization: Anti-VEGF Drug Therapy Strategy Based on Vascular Geometry Diagnosed by OCTA.},
journal = {Clinical case reports},
volume = {13},
number = {10},
pages = {e71250},
pmid = {41132628},
issn = {2050-0904},
abstract = {Macular neovascularization (MNV), a hallmark of several retinal disorders including ocular trauma and wet age-related macular degeneration, remains a major cause of vision impairment due to the proliferation of abnormal, fragile blood vessels. Anti-VEGF therapies, such as Aflibercept (Eylea), Bevacizumab (Avastin), Brolucizumab (Beovu), Conbercept (Lumitin), Faricimab (Vabysmo), Ranibizumab (Lucentis), and Pegaptanib (Macugen), have significantly transformed MNV management, targeting VEGF to curb this pathological vascular growth. In this report, we describe a 63-year-old male with a history of hypertension and diabetes who developed acute vision loss attributed to MNV secondary to hypertensive retinopathy. Optical coherence tomography angiography (OCTA) revealed unusual heart-shaped, intertwined vascular nets, informing the choice of Conbercept for intravitreal injection. This personalized therapeutic decision led to marked visual improvement over a 12-month period. The case exemplifies the importance of vascular geometry in guiding anti-VEGF selection, supported by existing literature that links specific neovascular geometries to differential drug responsiveness. Conbercept, in particular, proved effective against the complex intertwined nets observed in this patient. These findings emphasize the promise of individualized treatment strategies and the potential of OCTA-based vascular geometry classification as a tool for precision medicine.},
}
@article {pmid41132126,
year = {2025},
author = {Schmidt-Erfurth, U and Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Scheibler, L and Bogunovic, H},
title = {Plain language summary of disease activity and therapeutic response to pegcetacoplan for geographic atrophy identified by deep learning-based analysis of OCT.},
journal = {Immunotherapy},
volume = {17},
number = {14},
pages = {971-981},
doi = {10.1080/1750743X.2025.2569302},
pmid = {41132126},
issn = {1750-7448},
}
@article {pmid41131329,
year = {2025},
author = {Peto, T and Pearce, I and Talks, J and de Salvo, G and Patel, PJ and de Silva, SR and Gale, RP and Sivaprasad, S and Varma, D and Reynolds, R and Bailey, C and Downey, L and Kiire, C and Chi, GC and Dodds, M and James, N and Downey, AK and Dayal, P},
title = {Real-world treatment patterns and visual outcomes of faricimab in patients with diabetic macular oedema in the UK at 12 months: the FARWIDE-DMO study.},
journal = {Eye (London, England)},
volume = {39},
number = {18},
pages = {3350-3358},
pmid = {41131329},
issn = {1476-5454},
mesh = {Humans ; *Visual Acuity ; *Diabetic Retinopathy/drug therapy/physiopathology/complications/diagnosis ; Female ; Male ; *Macular Edema/drug therapy/physiopathology/etiology/diagnosis ; Intravitreal Injections ; United Kingdom/epidemiology ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Middle Aged ; Treatment Outcome ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: The Faricimab Real-World Evidence (FARWIDE) studies are evaluating real-world outcomes of eyes with diabetic macular oedema (DMO)/neovascular age-related macular degeneration (nAMD) treated with faricimab in the UK. We present results from FARWIDE-DMO for eyes with 12 months of follow-up after faricimab initiation.<br><br>METHODS: FARWIDE-DMO includes patients with diagnosis of DMO who received &#x2265;1 intravitreal faricimab injection after May 2022 in the diagnosed eye(s) at 1 of 35 UK National Health Service sites. All eyes had &#x2265;12 months of follow-up after faricimab initiation as of July 2024. Treatment-na&#xef;ve (TN) eyes had no prior anti-VEGF therapy or steroid implant. Previously treated (PT) eyes switched to faricimab. Baseline characteristics, visual acuity (VA) outcomes and treatment patterns were evaluated. Intraocular inflammation (IOI) and presumed infectious endophthalmitis (PIE) incidences were pooled for all nAMD/DMO eyes with any follow-up duration. Analyses are descriptive.<br><br>RESULTS: 2147 eyes (1564 patients) were included (TN, 32.1%; PT, 67.9%). For TN eyes, mean (standard deviation [SD]) VA at baseline and 12 months were 63.9 (15.2) and 68.4 (16.3) Early Treatment Diabetic Retinopathy Study letters, respectively. VA remained stable in PT eyes. TN eyes received a mean (SD) of 4.5 (1.0) faricimab injections in months 1-6 and 1.9 (1.2) injections in months 7-12. PT eyes received 4.5 (1.2) injections in months 1-6 and 2.4 (1.3) in months 7-12. IOI and PIE rates were consistent with faricimab phase 3 trials.<br><br>CONCLUSIONS: These 1-year data support real-world effectiveness, durability and safety of faricimab in DMO.},
}
@article {pmid41131180,
year = {2025},
author = {Graham, F},
title = {Daily briefing: People with macular degeneration can read again after retinal implant.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/d41586-025-03442-5},
pmid = {41131180},
issn = {1476-4687},
}
@article {pmid41130930,
year = {2025},
author = {Ostrovsky, M and Tuli, R and Kozlov, Y and Robart, ACW and Ruparelia, S and Lebreton, L and Gou, A and Shoham-Hazon, N and Lee, TKM and Berco, E},
title = {To ac tap or not to ac tap: Multi-centre outcomes of patients receiving anti-VEGF injections.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251389427},
doi = {10.1177/11206721251389427},
pmid = {41130930},
issn = {1724-6016},
abstract = {PurposeTo compare intraocular pressure (IOP) and retinal nerve fibre layer (RNFL) thickness in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) injections with and without anterior chamber paracentesis (ACP).MethodsThis multicentre retrospective cohort study included 269 injection-naïve eyes from 210 patients with neovascular age-related macular degeneration (AMD) or diabetic macular oedema (DME). A matched subset of 140 eyes (70 with ACP, 70 without) was selected based on age, sex, diagnosis, laterality, and number of injections. RNFL thickness (overall and by quadrant) was measured at baseline and one-year follow-up. Additional outcomes included IOP, visual acuity (VA), and central retinal thickness (CRT).ResultsThe matched cohort had a mean age of 71.06 ± 11.44 years, with 61.4% female participants. ACP eyes had worse baseline VA, higher IOP, and thicker CRT (p < 0.050, for all), but showed greater VA improvement (p = 0.023) and a trend towards greater CRT reduction (p = 0.061). RNFL thinning over one year did not differ between the groups (-3.24 ± 11.82 µm vs -2.95 ± 7.81 µm, p = 0.883). No major complications were observed.ConclusionACP did not significantly reduce RNFL thinning over one year but was well tolerated. It may be considered in patients at higher risk from transient IOP elevations. Future prospective studies are warranted to clarify its role in specific patient subgroups.},
}
@article {pmid41130334,
year = {2025},
author = {Li, HY and Dong, L and Shao, L and Wei, WB},
title = {Multiomics data reveal microglia's promotion for choroidal neovascularization in endothelial cells.},
journal = {Experimental eye research},
volume = {262},
number = {},
pages = {110701},
doi = {10.1016/j.exer.2025.110701},
pmid = {41130334},
issn = {1096-0007},
abstract = {Choroidal neovascularization (CNV) stands as one of the leading causes of blindness worldwide, driven by the dysregulation of key signaling pathways, including vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β). This study aimed to elucidate the specific cell types within the retina and retinal pigment epithelium (RPE)/choroid complex that contribute to CNV progression, as well as to explore how the expression levels of cysteine-rich protein 2 (CSRP2), a downstream effector, are altered in the pathological mechanisms underlying CNV. By investigating these molecular and cellular dynamics, we seek to provide deeper insights into the disease's progression and identify potential therapeutic targets. Retinal tissues, RPE/choroid complexes, and blood samples from both age-related macular degeneration (AMD) caused CNV patients and healthy controls were obtained from the GEO database for differential gene expression analysis. Integrated analysis of tissue and blood samples from wet AMD patients and healthy controls identified CSRP2 as a critical biomarker gene associated with pathogenesis. To uncover potential underlying mechanisms, we conducted immune infiltration analysis and further validated our findings using single-cell RNA sequencing (scRNA-seq) data from the GEO database. Additionally, scRNA-seq data were utilized to investigate cell-cell communication networks and perform Gene Set Enrichment Analysis (GSEA). scRNA-seq analysis demonstrated that CSRP2 was significantly upregulated in microglia and endothelial cells, with concurrent activation of the VEGF and TGF-β signaling pathways. Microglia emerged as a central hub for outgoing interactions, while endothelial cells were identified as the primary target of incoming signals within these pathways. GSEA further implicated CSRP2 in CNV progression, highlighting its role in angioimmunoblastic regulated by VEGF and TGF-β signaling pathways. In the in-vitro experiments, we found that activated microglia stimulated VEGFA, TGF-β and CSRP2, which enhanced angiogenesis, migration, proliferation, permeability, and altered the phenotype of co-cultured choroidal endothelial cells. These findings underscore the pivotal involvement of CSRP2 in mediating cellular crosstalk and signaling dynamics critical to CNV development. Microglia and endothelial cells emerged as the primary cell clusters interacting under this signaling regulation, driving angiogenesis and contributing to the pathological progression of CNV. The findings provide promise alternative therapy for CNV patients casued by AMD.},
}
@article {pmid41129903,
year = {2025},
author = {Rajendran, N and Singh, A and Runyon, W and Hu, S and Kumar, R and Ratnapriya, R and Csaky, K and Sripathi, SR},
title = {Derivation of pluripotent stem cell lines (RFSCi005-A, RFSCi006-A) from siblings harboring identical high-risk complement variants with discordant age-related macular degeneration.},
journal = {Stem cell research},
volume = {89},
number = {},
pages = {103852},
doi = {10.1016/j.scr.2025.103852},
pmid = {41129903},
issn = {1876-7753},
abstract = {Age-related macular degeneration (AMD) is a complex disease influenced by genetic and environmental factors. Variants in the complement pathway, especially in the CFH gene, increase AMD risk, yet disease severity can differ among individuals with identical high-risk genotypes. We generated induced pluripotent stem cell (iPSC) lines from siblings carrying identical high-risk complement variants but displaying discordant AMD phenotypes. These lines provide a unique platform to study epigenetic, transcriptomic, and environmental factors driving AMD heterogeneity. By comparing differentiated retinal cells, we aim to reveal mechanisms behind variable disease susceptibility and inform personalized therapies for AMD.},
}
@article {pmid41129178,
year = {2025},
author = {Alkabbani, W and Cromer, SJ and Patorno, E},
title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.3720},
pmid = {41129178},
issn = {2168-6173},
}
@article {pmid41129172,
year = {2025},
author = {Feldman-Billard, S and Girmens, JF and Ayello-Scheer, S},
title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.3717},
pmid = {41129172},
issn = {2168-6173},
}
@article {pmid41129166,
year = {2025},
author = {Mammo, DA and Talcott, KE and Singh, RP},
title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.3714},
pmid = {41129166},
issn = {2168-6173},
}
@article {pmid41129165,
year = {2025},
author = {Ziemssen, F and Helbig, H},
title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.3711},
pmid = {41129165},
issn = {2168-6173},
}
@article {pmid41129138,
year = {2025},
author = {Talcott, KE and Rachitskaya, AV and Singh, RP},
title = {Glucagon-Like Peptide-1 Receptor Agonist Use and Age-Related Macular Degeneration-Where Do We Stand?.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.4090},
pmid = {41129138},
issn = {2168-6173},
}
@article {pmid41129133,
year = {2025},
author = {Ahuja, AS and Paredes, AA and Young, BK},
title = {Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41129133},
issn = {2168-6173},
abstract = {IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown.<br><br>OBJECTIVE: To evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs).<br><br>This retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities. Data were analyzed on March 21, 2025, and August 2, 2025.<br><br>EXPOSURES: Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching.<br><br>RESULTS: A total of 91&#x202f;408 patients were included. After propensity score matching for the primary analysis, 45&#x202f;704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35&#x202f;753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35&#x202f;732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P&#x2009;<&#x2009;.001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P&#x2009;<&#x2009;.001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P&#x2009;<&#x2009;.001). No differences were observed in progression to exudative AMD.<br><br>CONCLUSIONS AND RELEVANCE: In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations.},
}
@article {pmid41129131,
year = {2025},
author = {Shor, R and Popovic, MM and Muni, RH},
title = {Neovascular Age-Related Macular Degeneration and GLP-1 RAs-Reply.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.3723},
pmid = {41129131},
issn = {2168-6173},
}
@article {pmid41125297,
year = {2025},
author = {Li, Z and Pan, Z and Huang, Y and Xie, H and Wu, X and Zhang, C and Wong, TY and Jonas, JB and Wang, YX},
title = {Cigarette smoking and retinal ganglion cell layer and photoreceptor outer segment thickness: The Beijing Eye Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2024-326789},
pmid = {41125297},
issn = {1468-2079},
abstract = {PURPOSE: To examine an association of cigarette smoking on retinal layer thickness.<br><br>METHODS: The population-based Beijing Eye Study 2011 included 3468 individuals aged 50+ years. All participants underwent optical coherence tomography (OCT) of the macula. Using a multiple-surface OCT segmentation algorithm, the retina was segmented into nine layers. Information about cigarette smoking was assessed in an interview with a standardised questionnaire. The exclusion criterion was the presence of any retinal or optic nerve disease.<br><br>RESULTS: The study included 2173 participants (mean age: 61.7&#xb1;8.4 years; mean axial length: 23.1&#xb1;0.8&#x2009;mm) with 660 (30.4%) participants with a smoking history and 1513 (69.6%) non-smokers. Mean duration of the smoking period was 8.7&#xb1;14.9 years, and mean smoking quantity was 9.5&#xb1;18.2 pack-years. In multivariable analysis, higher prevalence of smoking was associated with thinner whole retina (p=0.024; B=-1.64; 95% CIs -3.07 to -0.22), thinner ganglion cell layer (GCL) (p=.044; B=-0.39; 95%&#x2009;CI -0.78 to -0.01) and thinner photoreceptor outer segment layer (POS) (p=0.024; B=-0.38; 95%&#x2009;CI -0.72 to -0.05) with adjustments of age, gender, axial length, education level and hypertension. Similar results were obtained if the retinal thickness measurements were obtained in the various macular subfields. A longer period of smoking was related to thinner whole retina (p=0.009; B=-0.06; 95%&#x2009;CI -0.10 to -0.01), thinner retinal nerve fibre layer (RNFL) (p=0.011; B=-0.01; 95%&#x2009;CI -0.02 to -0.002), thinner GCL (p=0.006; B=-0.02; 95%&#x2009;CI -0.03 to -0.01) and thinner POS (p=0.025; B=-0.01; 95%&#x2009;CI -0.02 to -0.001) with adjustments of age, gender, axial length, education level and hypertension. Higher smoking pack-years were significantly associated with thinner GCL (p=0.022; B=-0.01; 95%&#x2009;CI -0.02 to -0.002).<br><br>CONCLUSIONS: Smoking was related to thinner GCL and POS in this population-based investigation, pointing towards and agreeing with an association between smoking and optic nerve damage or age-related macular degeneration.},
}
@article {pmid41124203,
year = {2025},
author = {Holz, FG and Le Mer, Y and Muqit, MMK and Hattenbach, LO and Cusumano, A and Grisanti, S and Kodjikian, L and Pileri, MA and Matonti, F and Souied, E and Stanzel, BV and Szurman, P and Weber, M and Bartz-Schmidt, KU and Eter, N and Delyfer, MN and Girmens, JF and van Overdam, KA and Wolf, A and Hornig, R and Corazzol, M and Brodie, F and Olmos de Koo, L and Palanker, D and Sahel, JA},
title = {Subretinal Photovoltaic Implant to Restore Vision in Geographic Atrophy Due to AMD.},
journal = {The New England journal of medicine},
volume = {},
number = {},
pages = {},
pmid = {41124203},
issn = {1533-4406},
support = {NIHR203322/DH_/Department of Health/United Kingdom ; },
abstract = {BACKGROUND: Geographic atrophy due to age-related macular degeneration (AMD) is the leading cause of irreversible blindness and affects more than 5 million persons worldwide. No therapies to restore vision in such persons currently exist. The photovoltaic retina implant microarray (PRIMA) system combines a subretinal photovoltaic implant and glasses that project near-infrared light to the implant in order to restore sight to areas of central retinal atrophy.<br><br>METHODS: We conducted an open-label, multicenter, prospective, single-group, baseline-controlled clinical study in which the vision of participants with geographic atrophy and a visual acuity of at least 1.2 logMAR (logarithm of the minimum angle of resolution) was assessed with PRIMA glasses and without PRIMA glasses at 6 and 12 months. The primary end points were a clinically meaningful improvement in visual acuity (defined as &#x2265;0.2 logMAR) from baseline to month 12 after implantation and the number and severity of serious adverse events related to the procedure or device through month 12.<br><br>RESULTS: A total of 38 participants received a PRIMA implant, of whom 32 were assessed at 12 months. Of the 6 participants who were not assessed, 3 had died, 1 had withdrawn, and 2 were unavailable for testing. Among the 32 participants who completed 12 months of follow-up, the PRIMA system led to a clinically meaningful improvement in visual acuity from baseline in 26 (81%; 95% confidence interval, 64 to 93; P<0.001). Using multiple imputation to account for the 6 participants with missing data, we estimated that 80% (95% CI, 66 to 94; P<0.001) of all participants would have had a clinically meaningful improvement at 12 months. A total of 26 serious adverse events occurred in 19 participants. Twenty-one of these events (81%) occurred within 2 months after surgery, of which 20 (95%) resolved within 2 months after onset. The mean natural peripheral visual acuity after implantation was equivalent to that at baseline.<br><br>CONCLUSIONS: In this study involving 38 participants with geographic atrophy due to AMD, the PRIMA system restored central vision and led to a significant improvement in visual acuity from baseline to month 12. (Funded by Science Corporation and the Moorfields National Institute for Health and Care Research Biomedical Research Centre; PRIMAvera ClinicalTrials.gov number, NCT04676854.).},
}
@article {pmid41123658,
year = {2025},
author = {Chakravarthy, U and Foss, AJE and Panos, GD and Peto, T and Rotsos, T and Sadda, S and De Cock, E and Empeslidis, T},
title = {Management of fibrosis in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41123658},
issn = {1435-702X},
abstract = {Subretinal fibrosis is a common end-stage sequela of neovascular age-related macular degeneration (nAMD), and it is associated with poor long-term visual outcomes. The pathogenesis of subretinal fibrosis in nAMD is largely driven by epithelial-mesenchymal and endothelial-mesenchymal transition within the retinal pigment epithelium and endothelium of the choroidal circulation. Upregulation of vascular endothelial growth factor (VEGF) expression further contributes to the observed fibrovascular content and increased vascular permeability. There is a substantial need for direct therapeutic strategies for fibrosis in nAMD, including anti-fibrotic agents. Until direct treatment strategies are developed, the management of nAMD using anti-VEGF agents must be optimized. However, fibrosis can occur in some patients otherwise successfully treated with anti-VEGF therapy, resulting in the loss of previous visual acuity (VA) gains experienced after treatment initiation. This review summarizes the current understanding of the mechanisms driving fibrosis in nAMD, risk factors for fibrosis development, and limitations of current detection methods. Available evidence on how different factors relating to anti-VEGF therapy (e.g., specific agent, delays in administration, extended administration intervals, dosing or treatment regimen) and the early detection of nAMD impact the risk of fibrosis is also discussed. Lastly, insights into potential future directions for the management of fibrosis in nAMD, particularly the development of anti-fibrotic agents, are deliberated.},
}
@article {pmid41122527,
year = {2025},
author = {Bates, BA and Mansour, HA and Al-Khersan, H and Wood, E and Momenaei, B and Schneider, E and Richards, CJ and DeYoung, C and Wykoff, CC and Quinn, K and Hsu, J and Regillo, CD and Ho, AC and Fineman, MS and Klufas, MA and Storey, PP},
title = {The Efficacy and Safety of Intravitreal Aflibercept 8 mg in Clinical Practice.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251383384},
pmid = {41122527},
issn = {2474-1272},
abstract = {Purpose: To characterize real-world use of intravitreal aflibercept 8 mg across 22 US retina practices. Methods: Retrospective review of patients who received at least 1 intravitreal aflibercept 8 mg injection for treatment of neovascular age-related macular degeneration, diabetic macular edema, or diabetic retinopathy through April 1, 2024. Data from health records were collected retrospectively, including best-corrected visual acuity (BCVA), interval between treatments, and adverse events. Results: A total of 8323 eyes of 6271 patients received 20 385 intravitreal aflibercept 8 mg injections. A total of 669 eyes (8.0%) were not previously treated. Among treatment-naive eyes, mean logMAR BCVA improved from 0.57 (Snellen equivalent ~20/80) at the time of the first intravitreal aflibercept 8 mg injection, to 0.47 (Snellen equivalent ~20/60) (P < .001), 0.46 (Snellen equivalent ~20/60) (P < .001), and 0.48 (Snellen equivalent ~20/60) (P = .012) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Among previously treated eyes, mean logMAR BCVA improved from 0.46 (Snellen equivalent ~20/60) at the time of the first intravitreal aflibercept 8 mg injection, to 0.42 (Snellen equivalent ~20/50) (P < .001), 0.43 (Snellen equivalent ~20/50) (P < .001), and 0.45 (Snellen equivalent ~20/60) (P = .70) at the second, third, and fourth intravitreal aflibercept 8 mg injections, respectively. Treatment intervals to time of second, third, and fourth intravitreal aflibercept 8 mg injections increased compared to baseline intervals, by a mean of 2.2 days (P < .001), 2.5 days (P < .001), and 13.5 days (P < .001), respectively. Intraocular inflammation was observed in 11 eyes (1 in 1853 injections). Nine eyes (1 in 2265 injections) developed suspected endophthalmitis. Conclusions: In this real-world clinical setting, intravitreal aflibercept 8 mg treatment demonstrated improvements in BCVA outcomes, with increased intervals between injections. Rates of intraocular inflammation and endophthalmitis were low.},
}
@article {pmid41122382,
year = {2025},
author = {Wang, W},
title = {LLM-based multi-agent system for neuro-ophthalmic diagnosis and personalized treatment planning.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1688509},
pmid = {41122382},
issn = {1662-4548},
abstract = {INTRODUCTION: Ophthalmic findings can non-invasively reflect nervous-system status. We present an LLM-based multi-agent framework that preserves diagnostic uncertainty to support neuro-ophthalmic screening and referral.<br><br>METHODS: Heterogeneous inputs (clinical text/PDFs and optional fundus/OCT images) are normalized by an Information Collection Agent. A Diagnosis Agent ensembles multiple LLMs and, when available, a CNN image branch; outputs are aggregated with an uncertainty-aware fusion.<br><br>RESULTS: Across a curated ophthalmic corpus, the multi-agent framework improves robustness over single-model baselines and produces multi-candidate distributions suitable for downstream triage and monitoring.<br><br>DISCUSSION: Uncertainty-aware, multi-candidate predictions align with clinical decision-making under ambiguity and suggest future work on calibration and knowledge-layer fusion.},
}
@article {pmid41120131,
year = {2025},
author = {Phan, LT and Hong, T and Chang, JH and Mehta, H and Fraser-Bell, S and Cheung, GCM and Broadhead, GK and Chang, AA},
title = {A prospective, open-label, single-arm, investigator-initiated clinical trial to assess the efficacy, safety and durability of faricimab in patients with inadequate response to current treatment for neovascular age-related macular degeneration: protocol design and rationale for the FURGGHORN Study.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {41120131},
issn = {2397-3269},
mesh = {Aged ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Multicenter Studies as Topic ; Prospective Studies ; Research Design ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Clinical Trials, Phase IV as Topic ; Antibodies, Bispecific ; },
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor therapy has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). However, some patients face recurrent and persistent disease activity despite ongoing treatment. Faricimab (trade name: Vabysmo) is a recently approved therapy which targets two pathways involved in nAMD. This study aims to assess changes in best-corrected visual acuity (BCVA) and treatment frequency among patients currently treated for nAMD who switch to intravitreal faricimab therapy under a treat-and-extend regimen.<br><br>METHODS AND ANALYSIS: The FURGGHORN Study is a prospective, open-label, single-arm, multicentre investigator-initiated clinical trial. 102 patients with nAMD meeting inclusion criteria were recruited from 12 clinical sites across Australia and Singapore. Following 4&#x2009;monthly loading doses of faricimab, treatment intervals were adjusted according to a regimen developed based on real-world practice patterns and consensus guidelines. The primary endpoint is the change from BCVA at week 52. Secondary endpoints include the proportions of patients at different treatment intervals, changes in central macular thickness and retinal fluid dimensions.<br><br>ETHICS AND DISSEMINATION: This study was designed, implemented and reported in accordance with the International Conference on Harmonisation Harmonised Tripartite Guidelines for Good Clinical Practice, with applicable local regulations and with the ethical principles laid down in the Declaration of Helsinki. Ethics approval was obtained from Bellberry Limited (2022-12-1388), St Vincent's Hospital Human Research Ethics Committee (2023/STE01568) and Singhealth Centralized Institutional Review Board (2023-2190). Results will be disseminated at scientific meetings and through peer-reviewed publications.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12623000215628.},
}
@article {pmid41117364,
year = {2025},
author = {García-Serrano Fuertes, R and Romero Martínez, A and Suarez Pérez, J and López Herrero, F and Cabanás Jiménez, M and Flores Córdoba, A and Sánchez Vicente, JL},
title = {Cost-effectiveness analysis of Brolucizumab compared to Aflibercept and Ranibizumab in nAMD with persistent retinal fluid.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251388170},
doi = {10.1177/11206721251388170},
pmid = {41117364},
issn = {1724-6016},
abstract = {Purpose of the researchThis study aimed to evaluate the cost-effectiveness of Brolucizumab in patients with exudative age-related macular degeneration (AMD) and persistent retinal fluid unresponsive to previous therapies, within the context of a real-world clinical practice setting in a Spanish referral hospital. Furthermore, the study examined the probabilities of transitioning between therapies.Major findingsA 6-month treatment projection demonstrated that Brolucizumab was not cost-effective compared to Ranibizumab (incremental cost-effectiveness ratio [ICER]: -12.98) and Aflibercept (ICER: -47.64). Conversely, when assessing only drug and administration visit costs, Brolucizumab appeared cost-effective (ICER of 9.14 versus Aflibercept and 35.01 versus Ranibizumab). The increased burden of follow-up costs, which were €348.96 higher than those for Ranibizumab and €174.48 higher than Aflibercept, likely drove the trend towards non-cost-effectiveness. Additionally, the analysis indicated a 43% probability of transitioning to Faricimab within the studied population.ConclusionsBrolucizumab was determined to be not cost-effective compared to Ranibizumab and Aflibercept in patients with exudative AMD and persistent retinal fluid, primarily due to a higher number of follow-up visits necessitated by its safety profile. Furthermore, newly observed vitreous opacities and a tendency towards the use of Faricimab were noted.},
}
@article {pmid41117255,
year = {2025},
author = {Yang, W and Jia, J and Liu, X and Wan, P},
title = {Evaluating the Impact of Age-Related Macular Degeneration on Seasonal Affective Disorder: A Retrospective Cohort Study in a Chinese Population.},
journal = {Actas espanolas de psiquiatria},
volume = {53},
number = {5},
pages = {939-946},
pmid = {41117255},
issn = {1578-2735},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Seasonal Affective Disorder/complications/psychology/epidemiology ; *Macular Degeneration/complications/psychology ; China/epidemiology ; Aged ; Middle Aged ; Life Style ; East Asian People ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) usually affects the macular region of the retina, while seasonal affective disorder (SAD) is a complex mental disorder. However, the interaction between these two clinical conditions remains unexplored. Therefore, this study aimed to explore the influence of AMD on SAD and to assess the correlation of ocular pathology with lifestyle and mental health factors.<br><br>METHODS: This study recruited 158 AMD patients admitted to the Second Affiliated Hospital of Xi'an Medical University, China, between January 2020 and October 2023. Based on their affection status, the patients were divided into two groups: the SAD group (n = 58) and the non-SAD group (n = 100). Baseline characteristics, including blood pressure, hematological parameters, ocular parameters, and lifestyle factors, were compared between the two groups to evaluate the potential influence of AMD on SAD.<br><br>RESULTS: We observed specific differences in the family history of mental illness between the non-SAD and SAD groups (p < 0.001). However, the two groups' other baseline characteristics, such as blood pressure and hematological parameters, were comparable (p > 0.05). Additionally, significant differences were also observed in central retinal thickness (CRT), choroidal thickness, lesion atrophy area, and macular volume between the two groups (p < 0.001). Moreover, intraocular pressure (IOP) did not reveal a~significant difference between the two groups (p > 0.05). Compared with the SAD group, the non-SAD group had significantly better vision, longer exercise duration, sunlight exposure time, outdoor activity, and lower sedentary behavior (all p < 0.001). The logistic regression analysis indicated that increased macular volume (odds ratio (OR) = 3.054, p = 0.008) and sedentary behavior (OR = 4.382, p < 0.001) significantly increased SAD risk. Additionally, the absence of a family history of mental illness did not reach statistical significance (OR = 0.375, p = 0.129), but a specific correlation was still observed.<br><br>CONCLUSION: This study shows a correlation between SAD and AMD. The significant differences in ocular pathological characteristics, lifestyle factors, and mental health status between the SAD and non-SAD groups suggest the crucial role of visual function and lifestyle in regulating mood and circadian rhythm in AMD patients.},
}
@article {pmid41117141,
year = {2025},
author = {Chen, C and Zhu, M and Fan, X and Lv, K and Jiang, K and Zhang, Y and Zhang, H and Qi, X and Lee, BT and Wan, Y and Wei, G and Liu, K and Xu, X},
title = {Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti-VEGFA Nanobody and Proprietary Penetratin Analog Formulation.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e04660},
doi = {10.1002/advs.202504660},
pmid = {41117141},
issn = {2198-3844},
support = {82271096//National Natural Science Foundation of China/ ; 81800835//National Natural Science Foundation of China/ ; 82273864//National Natural Science Foundation of China/ ; 21S11905300//Shanghai Science and Technology Program/ ; 21ZR1407100//Shanghai Science and Technology Program/ ; 18YF1419700//Shanghai Sailing Program/ ; //Shanghai Talent Development Fund/ ; //Shanghai Jiao Tong University K. C. Wong Medical Fellowship Fund/ ; //Lumitin Vision to Brightness Research Funding/ ; },
abstract = {Pathological retinal and choroidal neovascularization is a hallmark of several blinding diseases, including diabetic retinopathy and age-related macular degeneration. While intravitreal anti-VEGF therapies remain the standard of care, they necessitate frequent injections, posing risks such as endophthalmitis and elevated intraocular pressure, alongside economic and adherence challenges. Here, we present Pene/LQ015, a novel eye drop formulation comprising the anti-VEGFA nanobody (LQ015) and a proprietary penetratin analog for noninvasive delivery. LQ015 demonstrates superior VEGF-blocking activity, broad binding specificity across species, and robust stability and scalability using a yeast expression system. Topical administration of Pene/LQ015 achieved effective retinal-choroid complex drug levels and suppressed neovascularization in preclinical models. Notably, in the cynomolgus monkey laser-induced choroidal neovascularization model, 30 days of continuous topical application significantly reduced neovascularization and vascular leakage, with excellent safety and tolerability. These findings highlight Pene/LQ015's potential as a game-changer in treating neovascular eye diseases. It offers a groundbreaking, noninvasive alternative to intravitreal injections, addressing key limitations of current therapies by enabling continuous dosing, improving patient adherence, and reducing treatment burden. These findings underscore its potential to transform the management of neovascular retinal and choroidal diseases, with promising implications for clinical application.},
}
@article {pmid41114788,
year = {2025},
author = {Zhou, Y and Liu, C and Yin, J and Zhao, D and Xue, F},
title = {From environmental exposure to retinal pathology: epidemiological and mechanistic insights into multi-metal driven ocular diseases.},
journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine},
volume = {},
number = {},
pages = {},
pmid = {41114788},
issn = {1572-8773},
abstract = {With aging and environmental pollution, heavy metal exposure has become a growing concern for age-related eye diseases. However, the relationship between heavy metals and age-related macular degeneration (AMD), cataracts, glaucoma, and diabetic retinopathy (DR) remains unclear. This study investigates the association between urinary heavy metals and these eye diseases, focusing on the molecular mechanisms of cadmium (Cd) in driving AMD. Data from the 2005-2008 NHANES (n = 1865) were analyzed using multivariable logistic regression, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS) modeling, and sensitivity analyses. Potential molecular mechanisms of Cd in AMD were explored via intersection gene screening, protein-protein interaction network construction, and GO/KEGG enrichment analyses. In single-metal exposure models, Cd was significantly associated with AMD (OR = 1.563, 95% CI: 1.177-2.077, P = 0.00205), Co with cataract (OR = 1.386), U with glaucoma (OR = 1.300), and As with DR (OR = 1.214). In the WQS model, only AMD remained significantly associated with the overall metal mixture (OR = 1.89, 95% CI: 1.22-2.91, P = 0.0041). BKMR identified Cd as the most influential contributor to AMD (PIP = 0.523). The exposure-response curve for Cd and AMD demonstrated an upward trend, with the risk of AMD increasing as Cd exposure levels rose. Additionally, the overall metal mixture was positively associated with AMD risk. Subgroup and RCS analyses confirmed the stability of results, with no significant interaction across demographic subgroups. Sensitivity analyses further validated the findings: the highest quartile of Cd exposure was associated with increased AMD risk (OR = 2.45), and a significant dose-response trend was observed (P for trend = 0.0187). The association remained robust after excluding outliers (OR = 1.31, P = 0.0483).Mechanistically, Cd may induce retinal pigment epithelium damage via oxidative stress (SIRT1/TP53 axis), inflammation (TLR4/NF-κB pathway and pro-inflammatory cytokines), dysregulated apoptosis (BCL2/BAX imbalance), and hypoxia-induced metabolic disruption (HIF-1 signaling). Cd is an independent risk factor for AMD, likely acting through multiple toxic pathways. The effects of U, Co, and As may depend on exposure thresholds or confounders. These findings highlight the need for stricter Cd control and targeted antioxidant or anti-inflammatory strategies for age-related eye disease prevention and treatment.},
}
@article {pmid41112795,
year = {2025},
author = {Dhaliwal, KK and Simmons, J and Wong, A and Hudson, C and Wright, T and Ballios, BG and Bizheva, K},
title = {Visual stimulus-evoked transient blood flow and blood vessel diameter changes in the healthy human retina measured with a combined OCT+ERG system.},
journal = {Biomedical optics express},
volume = {16},
number = {10},
pages = {3958-3976},
pmid = {41112795},
issn = {2156-7085},
abstract = {Neurodegenerative retinal diseases, such as glaucoma, age-related macular degeneration and diabetic retinopathy, cause gradual damage to the retinal morphology, blood vasculature, and neuronal function, and ultimately lead to blindness. In this study, a retinal OCT system was combined with a clinical electroretinography (ERG) system to investigate visually-evoked transient changes in the retinal blood flow (RBF) and blood vessel diameter (BVD) in the healthy human retina. The OCT system offered 2.7 µm axial resolution in retinal tissue and 98 dB sensitivity for 1.1 mW imaging power and 250 kHz image acquisition rate. Doppler OCT (double circular scans around the optic nerve head) and ERG traces were acquired from healthy subjects in response to 10 Hz, white light flicker stimuli and different stimulus intensities. The ERG system was used to generate visual stimuli of precise timing, duration, luminance, and flicker frequency, as well as to confirm the retinal neuronal response to the visual stimulation. MATLAB-based custom algorithms were developed to track time-dependent changes in the RBF and BVD from the OCT images. Results from this study revealed a rapid transient increase in the RBF accompanied by transient vasoconstriction and vasodilation of the retinal blood vessels in response to the flicker stimulation. The amplitude and latency of the RBF and BVD responses were dependent on the stimulus intensity as well as the blood vessel type (arteries or veins).},
}
@article {pmid41111640,
year = {2025},
author = {Abukhaled, Y},
title = {Reactive oxygen species and oxidative stress in ocular disease: from molecular mechanisms to targeted therapies.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {14},
number = {3},
pages = {136-145},
pmid = {41111640},
issn = {2322-3219},
abstract = {BACKGROUND: Reactive oxygen species and oxidative stress are increasingly recognized as central drivers in the development of major ocular diseases, including cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy. The eye's unique environment-continuous light exposure, high oxygen tension, and abundant photosensitizers-renders it particularly vulnerable to ROS-mediated damage. This narrative review aims to synthesize current evidence on the molecular mechanisms of oxidative stress in ocular disease and highlight emerging therapeutic approaches.<br><br>METHODS: Targeted searches of PubMed, Scopus, and Google Scholar for literature published between 2000 and June 2025 were conducted. Keywords included "oxidative stress", "reactive oxygen species", "ocular disease", "cataract", "age-related macular degeneration", "glaucoma", and "diabetic retinopathy". Only English-language, peer-reviewed articles were considered. Relevant primary studies, clinical trials, reviews, and experimental reports were selectively incorporated, with an emphasis on recent publications and high-impact contributions to the field.<br><br>RESULTS: Evidence consistently demonstrates that ROS induce lipid peroxidation, protein oxidation, DNA damage, mitochondrial dysfunction, and disruption of redox-sensitive cellular signaling pathways across ocular tissues. In cataracts, oxidation of crystalline proteins and glutathione depletion are primary drivers of lens opacification. In age-related macular degeneration, mitochondrial dysfunction and lipofuscin accumulation promote retinal pigment epithelium degeneration and neovascularization. Glaucoma involves both trabecular meshwork oxidative injury, contributing to elevated intraocular pressure, and mitochondrial-driven retinal ganglion cell apoptosis. In diabetic retinopathy, hyperglycemia-induced ROS overload activates pathogenic pathways, leading to microvascular damage and neuronal dysfunction. Clinical and experimental studies support antioxidant therapies as adjunctive strategies, with the strongest evidence for Age-Related Eye Disease Study-based formulations in age-related macular degeneration and promising results for agents such as Coenzyme Q10 in glaucoma and sulforaphane in diabetic retinopathy. For cataracts, supplementation trials have yielded mixed outcomes and surgery remains the definitive treatment.<br><br>CONCLUSIONS: Oxidative stress represents a unifying mechanism in the pathogenesis of vision-threatening ocular diseases. Antioxidant-based interventions show potential, particularly when integrated with existing treatment regimens, but their translation into routine practice remains limited by heterogeneous trial results and the absence of robust biomarkers for patient selection. Future research should focus on precision antioxidant therapy, leveraging stage-specific interventions, novel delivery systems, and pathway-targeted compounds, to transform ocular care from reactive management toward prevention.},
}
@article {pmid41111635,
year = {2025},
author = {Koksaldi, S and Karti, O and Saatci, AO},
title = {Anti-vascular endothelial growth factor therapies in ophthalmology.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {14},
number = {3},
pages = {107-135},
pmid = {41111635},
issn = {2322-3219},
abstract = {BACKGROUND: Retinal diseases, including neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, are leading causes of vision loss worldwide. The introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies has dramatically changed the management of these conditions, offering targeted treatment that can preserve and even improve vision. We aimed to provide a comprehensive review of the development, clinical applications, and emerging indications of anti-VEGF therapies in ophthalmology, including biosimilar agents.<br><br>METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE for English-language articles published up to 31 July 2025. Additional sources were identified through manual screening of reference lists. Included studies spanned various designs: clinical trials, meta-analyses, observational studies, and preclinical research. Keywords used in the search strategy included terms such as "anti-VEGF therapy", "biosimilar pharmaceuticals", "intravitreal and intrastromal anti-VEGF injections", "retinal diseases" including "macular degeneration" and "retinal neovascularization", "ranibizumab", and "bevacizumab", as well as relevant MeSH terms where applicable.<br><br>RESULTS: Anti-VEGF agents have transformed the management of retinal diseases such as neovascular age-related macular degeneration, diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Newer agents such as brolucizumab and faricimab offer prolonged durability and enhanced anatomic outcomes, while biosimilars provide cost-effective alternatives. Anti-VEGF therapy has also shown promise in off-label or emerging indications such as neovascular glaucoma, corneal neovascularization, and other retinal or choroidal disorders including secondary macular edema and/or macular neovascularization associated with various forms of uveitis, diffuse choroidal hemangioma in Sturge-Weber Syndrome, hereditary retinal disorders such as fundus flavimaculatus, Coats-Like retinitis pigmentosa, Peripherin-2-associated retinopathy, immune checkpoint inhibitor use, radiation retinopathy, retinitis pigmentosa, Bietti crystalline dystrophy, autosomal recessive bestrophinopathy, melanocytoma-associated macular neovascular membrane, Best disease, Wyburn-Mason syndrome, choroidal osteoma, peripheral exudative hemorrhagic chorioretinopathy, traumatic choroidal rupture, torpedo maculopathy, optic disc melanocytoma, type 2 proliferative macular telangiectasia, and Coats disease. High-dose formulations and innovative delivery systems are under active investigation to reduce the treatment burden and extend dosing intervals.<br><br>CONCLUSIONS: Anti-VEGF therapies have revolutionized the field of ophthalmology, providing sight-saving treatment for a range of retinal diseases that were once considered untreatable or inevitably blinding. Today, anti-VEGF drugs are the go-to option for managing neovascular retinal disorders, thanks to their proven efficacy, favorable safety profile, and transformative impact on modern eye care.},
}
@article {pmid41110782,
year = {2025},
author = {Liu, H and Wong, DSL and Parikh, BH and Hao, M and Tan, QSW and Chee, PL and Lou, X and Kai, D and Lingam, G and Huang, D and Su, X and Liu, Z},
title = {Single-cell-pore-sized 3D printed scaffolds for retinal pigment epithelial cell therapy.},
journal = {Acta biomaterialia},
volume = {207},
number = {},
pages = {294-310},
doi = {10.1016/j.actbio.2025.10.033},
pmid = {41110782},
issn = {1878-7568},
mesh = {*Printing, Three-Dimensional ; *Tissue Scaffolds/chemistry ; *Retinal Pigment Epithelium/cytology/metabolism ; Humans ; Animals ; Rabbits ; Polyesters/chemistry ; Swine ; Porosity ; *Human Embryonic Stem Cells/cytology/metabolism ; *Cell- and Tissue-Based Therapy ; },
abstract = {Cell therapy is one of the most promising methods to treat retinal degenerative diseases, and crucial to its success is optimizing biomaterials to facilitate the delivery of retinal pigment epithelial (RPE) cells. This study explores the application of single-cell-pore-sized 3D printed polycaprolactone (PCL) scaffolds for cultivating human embryonic stem cell-derived RPE cell sheets. It compares them with track-etched polyethylene terephthalate (PET) membranes, the commercial products used in clinical trials for RPE cell delivery. We engineered two types of scaffolds at the microscale to optimize cell culture conditions, specifically focusing on pore size and fiber spacing. Protein expression analysis demonstrated that one scaffold with a pore size of ∼10 µm facilitated superior cellular integrity and function. Functional assessments, including barrier integrity, permeability, and phagocytosis assays, indicated that this scaffold enhanced nutrient exchange and maintained effective RPE functions akin to PET membranes. In an in vivo study, color fundus, optical coherence tomography, immunohistochemistry, and electroretinography revealed that 3D printed scaffolds exhibited biocompatibility, stability, and minimal inflammatory responses in the subretinal space of porcine models for 2 months and rabbit models for 14 months, with no adverse impact on retinal structure or function over either period. The findings suggest that 3D-printed biodegradable scaffolds present a viable alternative for RPE cell delivery, potentially advancing therapies for retinal degenerative conditions. STATEMENT OF SIGNIFICANCE: Cell therapy shows great promise for treating eye diseases that lead to vision loss. A crucial aspect of this therapy is delivering specialized retinal pigment epithelial (RPE) cells effectively. Our research presents a 3D-printed scaffold made from polycaprolactone (PCL), designed to carry RPE cells derived from human stem cells and dissolve after placement in the eye. We tested this scaffold in rabbits and pigs to evaluate its surgical handling, cell delivery effectiveness, and safety for human application. Our results refine implant design, paving the way for safer and more effective treatments for retinal diseases. Overall, this research enhances the application of cell therapy with scaffolds and offers valuable insights for future medical practices.},
}
@article {pmid41109779,
year = {2025},
author = {Lai, TYY and Kataoka, K and Hsieh, YT and Apte, RS and Bhende, M and Chang, A and Chaikitmongkol, V and Chen, Y and Chen, LJ and Cheung, GCM and Chhablani, J and Fong, KCS and Guymer, RH and Gomi, F and Huang, SS and Kim, JE and Kokame, GT and Koh, A and Li, X and Lim, JI and Ng, DSC and Okada, AA and Radke, NV and Sadda, SR and Sasaki, M and Sivaprasad, S and Shanmugam, MP and Verma, L and Wong, TY and Zhang, X and Lam, DSC},
title = {Corrigendum to "International consensuses and guidelines on etiology, diagnosis, treatment, and future developments of neovascular age-related macular degeneration (nAMD) by the Asia-Pacific Vitreo-retina Society (APVRS), the Asia-Pacific Ocular Imaging Society (APOIS) and the Academy of the Asia-Pacific Professors of Ophthalmology (AAPPO)" [Asia-Pac J Ophthalmol, Available online 29 August 2025, 100242 (2025) DOI:10.1016/j.apjo.2025.100242].},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100249},
doi = {10.1016/j.apjo.2025.100249},
pmid = {41109779},
issn = {2162-0989},
}
@article {pmid41108452,
year = {2025},
author = {Shen, LL and Applegate, CA and Rubin, GS and Sunness, JS},
title = {Patient-reported visual difficulties associated with geographic atrophy from age-related macular degeneration.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {412},
pmid = {41108452},
issn = {1573-2630},
support = {R01EY08552/NH/NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/complications/etiology ; Male ; Female ; *Visual Acuity/physiology ; Prospective Studies ; Aged ; *Macular Degeneration/complications/diagnosis/physiopathology ; *Vision Disorders/etiology/physiopathology/diagnosis ; Tomography, Optical Coherence/methods ; Surveys and Questionnaires ; Cross-Sectional Studies ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; },
abstract = {PURPOSE: To characterize visual difficulties associated with geographic atrophy (GA).<br><br>METHODS: A prospective study included 91 participants with bilateral GA. A visual activities questionnaire was administered at baseline and annually for 2&#xa0;years along with best-corrected visual acuity (BCVA) and GA size. Baseline questionnaire responses were compared using logistic regressions, and longitudinal changes were analyzed with generalized linear mixed-effect models. A small group of 12 participants with drusen without GA served as a comparison to participants with GA and good VA.<br><br>RESULTS: Compared to drusen participants, bilateral GA participants with BCVA of 20/50 or better reported significantly more difficulties in 8 vision-specific tasks. The frequencies of difficulty in reading small print, trouble with face recognition, and stopping driving were positively associated with GA severity cross-sectionally, measured by either BCVA or GA size, and increased over 2&#xa0;years (P&#x2009;<&#x2009;0.05 for each). Additional significant longitudinal changes included difficulty seeing in dim light (P&#x2009;=&#x2009;0.005) and locating a sign (P&#x2009;=&#x2009;0.008).<br><br>CONCLUSION: Reading, vision in dim illumination, face recognition, locating signs, and driving worsen over 2&#xa0;years in patients with GA, and may be the appropriate self-reported items to monitor in a clinical trial. These findings highlight the need for therapies addressing both GA enlargement and visual function decline.},
}
@article {pmid41108153,
year = {2025},
author = {Beckers, D and Lockington, D and Kretz, F and Beckers, L},
title = {Beyond the Label: Inconsistencies in AREDS2 Eye Supplements and a Call for Standardisation.},
journal = {Seminars in ophthalmology},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/08820538.2025.2577391},
pmid = {41108153},
issn = {1744-5205},
abstract = {PURPOSE: Age-related macular degeneration (AMD) remains a major cause of vision impairment among older adults globally. While treatment exists for the more aggressive, exudative form, options for managing nonexudative AMD are limited. One of the few interventions with scientific backing is the AREDS2 micronutrient formula, which has demonstrated an ability to slow disease progression in patients with intermediate AMD.This investigation set out to systematically assess over-the-counter supplements in the UK that are promoted for macular support, measuring how closely their contents align with the evidence-based AREDS2 formulation.<br><br>METHODS: Products marketed as beneficial for AMD were collected and analyzed. Their labeled ingredients and dosages were directly compared with the standardized nutrient profile outlined in the AREDS2 clinical trials.<br><br>RESULTS: The analysis revealed that most commercially available supplements deviated markedly from the AREDS2 formula. On average, vitamin C levels were 52.3% lower than recommended, vitamin E levels were 61.2% lower, and zinc content was reduced by 40.1%. Only a small subset of products fully matched both the composition and dosage of the reference formulation.<br><br>CONCLUSION: These findings highlight a significant gap between marketed claims and clinical evidence. Most supplements do not meet the established AREDS2 standards, potentially limiting their efficacy. Some were promoted specifically for AMD, while others used general "macular health" claims, adding to patient confusion. This inconsistency underscores the need for regulatory measures to enforce standardized labeling and formulation requirements to ensure informed clinical recommendations.},
}
@article {pmid41107523,
year = {2025},
author = {Gurudas, S and Marques, I and Girmens, JF and Lechanteur, Y and Parravano, M and Berger, L and Agostini, H and Barrão, S and Tsiroukis, E and Monés, J and Sararols, L and Silva, R and Scholl, HPN and Lommatzsch, A and Stanzel, B and Vujosevic, S and Sivaprasad, S and , },
title = {Baseline factors that are associated with change in visual acuity in intermediate AMD over two years in a multicentre cohort study in Europe- INTERCEPT-AMD Report 2.},
journal = {Eye (London, England)},
volume = {39},
number = {18},
pages = {3324-3332},
pmid = {41107523},
issn = {1476-5454},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Aged ; Aged, 80 and over ; Europe/epidemiology ; *Macular Degeneration/physiopathology/diagnosis ; Middle Aged ; Tomography, Optical Coherence ; Follow-Up Studies ; Retinal Drusen/physiopathology ; Cohort Studies ; },
abstract = {BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the change in visual acuity (VA) in participants with intermediate age-related macular degeneration (iAMD) over two years when categorised by the presence or absence of incomplete retinal and retinal pigment atrophy (iRORA) and subretinal drusenoid deposits (SDD).<br><br>SUBJECTS/METHODS: In this multicentre cohort study, participants with iAMD were classified as: i) iAMD with no iRORA or SDD; ii) iAMD with SDD with no iRORA; iii) iAMD with iRORA with no SDD and iv) iAMD with iRORA and SDD. The change in best recorded visual acuity (BRVA) over two years in the whole cohort and in each sub-category was analysed using linear mixed effect models employing an unstructured covariance structure. Associations with age, sex and baseline BRVA were evaluated.<br><br>RESULTS: 983 eyes from 805 participants were analysed. The mean baseline VA changed from 79.8 (SD 8.1) to 77.7 (SD 10.1) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at two years, with a mean unadjusted change in BRVA of -0.33 ETDRS letters (95% CI -0.72,0.06); P&#x2009;=&#x2009;0.10 at 6 months, -0.65 ETDRS letters (95% CI -1.14, -0.16); P&#x2009;=&#x2009;0.01 at 12 months, -1.45 ETDRS letters (95% CI -2.03, -0.86); P&#x2009;<&#x2009;.001 at 18 months and -2.16 ETDRS letters (95% CI -2.79, -1.53); P&#x2009;<&#x2009;.001 at 24 months. All sub-categories showed a small decline in BRVA. Increasing age and lower baseline visual acuity were associated with lower BRVA over two years.<br><br>CONCLUSION: Eyes with iAMD experience a small mean decline of ~2 letters over two years. Overall, these changes may not represent a clinically meaningful difference.},
}
@article {pmid41105576,
year = {2025},
author = {Hu, M and Li, X and Gong, Z and Yang, Y and Yin, C},
title = {The Bidirectional Casual Relationships between Chronic Inflammation and Intrinsic Capacity Decline: Insights from Mendelian Randomization Analysis.},
journal = {Gerontology},
volume = {},
number = {},
pages = {1-11},
doi = {10.1159/000548944},
pmid = {41105576},
issn = {1423-0003},
abstract = {INTRODUCTION: Intrinsic capacity, encompassing locomotion, vitality, cognition, psychology, and sensory function, is a critical determinant of healthy aging, yet its association with inflammatory markers remains poorly understood due to confounding factors in observational studies. We aimed to investigate the bidirectional causal relationships between chronic inflammation and intrinsic capacity decline by using Mendelian randomization (MR).<br><br>METHODS: We conducted a bidirectional MR analysis using summary-level data from large-scale genome-wide association studies (GWAS). Genetic variants significantly associated with five inflammatory markers (C-reactive protein [CRP], interleukin-1 receptor antagonist [IL-1RA], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-&#x3b1;], and white blood cell count [WBC]), and intrinsic capacity domains were used as instrumental variables. The inverse-variance weighted method was employed as the primary analysis, supplemented by sensitivity analyses such as MR-Egger, weighted median, and weighted mode methods.<br><br>RESULTS: Higher CRP levels were negatively associated with anxiety, hand grip strength, malnutrition, and usual walking pace but positively associated with macular degeneration. Elevated IL-1RA levels were associated with reduced cognitive performance, while higher WBC levels were linked to decreased hand grip strength and usual walking pace. Better cognitive performance, hand grip strength, and the usual walking pace were associated with lower CRP and WBC levels. The robustness of these findings was confirmed by sensitivity analyses.<br><br>CONCLUSION: Our study provides robust evidence for bidirectional causal relationships between chronic inflammation and intrinsic capacity decline, highlighting inflammation as a potential target for interventions to promote healthy aging. Future research is required to explore these relationships in more diverse populations and investigate therapeutic strategies to mitigate inflammation-related declines in intrinsic capacity.},
}
@article {pmid41105325,
year = {2025},
author = {Tillmann, A and Stillenmunkes, R and Garweg, JG and Cattaneo, J and Bartolomeo, N and Grimaldi, G and Spitznagel, T and De Oliveira Figueiredo, EC and Ambresin, A and Menghini, M and Somfai, GM and Zweifel, S and Fröhlich, J and Artemiev, D and Ebneter, A and Hatz, K and Weinberger, A and Pfister, IB and Schild, C and Eandi, C and Munk, MR and , },
title = {One-Year Outcomes of Faricimab in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {12},
pages = {3079-3091},
pmid = {41105325},
issn = {2193-8245},
abstract = {INTRODUCTION: This study evaluates the efficacy and safety of faricimab in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Data were retrospectively collected from 130 eyes of 118 patients across 11 centers of the Swiss Retina Research Network, all treated with faricimab using a treat-and-extend regimen and followed for 12 months between May 2022 and October 2024.<br><br>METHODS: Demographic data, visual and anatomical outcomes, treatment intervals, and adverse events were extracted from the electronic medical records over a 12-month follow-up period. Main outcomes included change in best corrected visual acuity (BCVA), central retinal thickness (CRT), presence of intra- and subretinal fluid, retinal pigment epithelial detachment (PED), injection intervals, and safety. Data are presented as mean&#x2009;&#xb1;&#x2009;standard deviation.<br><br>RESULTS: Twelve months after the initiation of faricimab therapy, mean BCVA improved from 64.6&#x2009;&#xb1;&#x2009;14.1 to 69.2&#x2009;&#xb1;&#x2009;20.3 ETDRS (Early Treatment of Diabetic Retinopathy Study) letters (p&#x2009;<&#x2009;0.001), while mean CRT decreased from 386.3&#x2009;&#xb1;&#x2009;172.3 to 246.6&#x2009;&#xb1;&#x2009;90.4&#xa0;&#x3bc;m (p&#x2009;<&#x2009;0.001). An early anatomical response to faricimab was observed in 34.6% of eyes achieving complete retinal fluid resolution after the first injection and in 55.6% after 12&#xa0;months. The mean treatment interval was extended to 10.5&#x2009;&#xb1;&#x2009;4.3&#xa0;weeks, with 26.2% of eyes achieving intervals of 8-11&#xa0;weeks and 39.2% achieving intervals of &#x2265;&#x2009;12&#xa0;weeks after 12&#xa0;months. Intraocular inflammation occurred in 0.77% of eyes (n&#x2009;=&#x2009;1, anterior uveitis); serious adverse events were not reported.<br><br>CONCLUSION: Faricimab demonstrates favorable anatomical and functional outcomes with extended treatment intervals in a majority of patients with treatment-na&#xef;ve nAMD, offering the potential of reduced treatment burden and the absence of retinal fluid in more than half of the subjects during the first year, while maintaining safety in a real-world setting.},
}
@article {pmid41103309,
year = {2025},
author = {Arnal, LI and Mesfin, Y and Ferreira, G and Salvi, A and Wai, KM and Koo, E and Kossler, AL and Koo, E and Rahimy, E and Mruthyunjaya, P and Ludwig, CA},
title = {The Association Between the Retinal Sequelae of Myopia and Glaucoma in a Global Cohort.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3749-3760},
pmid = {41103309},
issn = {1177-5467},
abstract = {PURPOSE: Discerning glaucoma in myopic eyes with tilted optic nerve discs is challenging given the atypical appearance and segmentation on optical coherence tomography. This study aims to determine the association between retinal sequelae of myopia and primary open-angle glaucoma (POAG). We hypothesize that retinal sequelae of myopia may aid in identifying high-risk glaucoma patients.<br><br>METHODS: An aggregated electronic health records research network was used to retrospectively identify 929,142 myopic patients. We evaluated the association of POAG with retinal sequelae of myopia, including choroidal neovascularization (CNV), myopic macular degeneration (MMD), foveoschisis, macular hole (MH), rhegmatogenous retinal detachment (RRD), and foveal retinal detachment (FRD). Logistic regressions estimated odds ratios (adjusted for age, sex, race, and ethnicity). Cox models estimated hazard ratios (additionally adjusted for pseudophakia).<br><br>RESULTS: FRD exhibited the strongest association with POAG (AOR: 5.82; 95% CI: 3.44-9.85), followed by foveoschisis (AOR: 3.10; 95% CI: 1.84-5.21) and MMD (AOR: 2.87; 95% CI: 2.19-3.75). Severe subtypes of POAG were also more highly associated with each retinal sequela than moderate and milder severity subtypes. Additionally, patients with each retinal sequela experienced a significantly faster progression from glaucoma suspect to POAG than those without these sequelae. Kaplan-Meier curves and adjusted Cox regression models suggested a faster progression from glaucoma suspect to POAG in those with foveoschisis (HR: 5.33; 95% CI: 2.21-12.85; p<0.005), CNV (HR: 1.73; 95% CI: 1.12-2.67; p=0.01), MMD (HR: 2.74; 95% CI: 1.47-5.10; p<0.005), MH (HR: 1.73; 95% CI: 1.29-2.31; p<0.005), and RRD (HR: 1.54; 95% CI: 1.28-1.86; p<0.005), whereas FRD was not significantly associated with glaucoma progression (HR: 1.28; 95% CI: 0.18-9.10; p=0.8).<br><br>CONCLUSION: The retinal sequelae of myopia are associated with the presence and progression of primary open-angle glaucoma. The presence of the retinal sequelae of myopia should cue ophthalmologists to refer such patients for glaucoma evaluation to encourage earlier detection and more targeted management.},
}
@article {pmid41102864,
year = {2025},
author = {Lombardo, M and Maccauro, C and D'Ambrosio, M and Grossi, M and Missiroli, F and Cesareo, M and Ricci, F},
title = {Aflibercept, ranibizumab, and bevacizumab for macular neovascularization secondary to age-related macular degeneration: a retrospective OCT-angiography study.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {111},
pmid = {41102864},
issn = {2056-9920},
abstract = {BACKGROUND: Intravitreal aflibercept, ranibizumab, and bevacizumab represent the three most widely used anti-VEGF agents for the treatment of neovascular age-related macular degeneration (AMD). The objective of this study is to compare the loading phase effects of these three agents on the macular neovascularization (MNV) area and flow in treatment-naïve eyes affected by neovascular AMD, utilizing optical coherence tomography angiography (OCTA).<br><br>METHODS: Eighty-four neovascular AMD eyes from eighty-four patients were included in this retrospective study. Twenty-five patients were treated with aflibercept, thirty-four with ranibizumab, and twenty-five with bevacizumab within the initial loading phase preceding a treat-and-extend regimen. All patients underwent a three-monthly injection loading phase and were evaluated at baseline and one month after the loading phase. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), MNV area, and MNV flow area were assessed. MNV parameters were measured using the device-integrated &#x201c;Flow Area&#x201d; tool and ImageJ software.<br><br>RESULTS: Average baseline BCVA and CRT were 0.60&#x2009;&#xb1;&#x2009;0.22 logMAR and 343&#x2009;&#xb1;&#x2009;46&#xa0;&#x3bc;m, respectively, and did not differ between groups. All three anti-VEGF agents improved anatomical and functional parameters, with no statistically significant differences between treatment groups (p&#x2009;>&#x2009;0.05). Aflibercept showed the most significant CRT reduction (88&#xa0;&#x3bc;m; p&#x2009;<&#x2009;0.01), while bevacizumab led to the highest BCVA gain (0.15 logMAR; p&#x2009;<&#x2009;0.01). MNV area significantly decreased only in the bevacizumab group (0.26 mm2; p&#x2009;<&#x2009;0.01), and flow area only in the ranibizumab group (0.23 mm2; p&#x2009;<&#x2009;0.05). A strong positive correlation between MNV areas and flow areas was found at baseline (r&#x2009;>&#x2009;0.8) and follow-up (r&#x2009;>&#x2009;0.9).<br><br>CONCLUSIONS: Aflibercept, ranibizumab, and bevacizumab demonstrated similar efficacy in reducing MNV area and flow and improving visual and anatomical outcomes after a three-injection loading phase. OCTA-derived flow area measurement may be a valuable and easily accessible tool in monitoring early treatment response.},
}
@article {pmid41102764,
year = {2025},
author = {Bottos, JM and Soares, ES and M Zimmer, CG and C Sinatti, VV and Q S Leal, CB and F Sallum, JM},
title = {RNA dysfunction in age-related macular degeneration: the role of U1 snRNP complex and neurodegenerative diseases.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {110},
pmid = {41102764},
issn = {2056-9920},
abstract = {BACKGROUND: Age-related macular degeneration (AMD), a leading cause of vision loss in elderly individuals, is a multifactorial disease driven by genetic, environmental, and cellular aging processes. Emerging evidence highlights the critical role of ribonucleic acid (RNA) splicing dysfunction in AMD pathogenesis, with a focus on the U1 small nuclear ribonucleoprotein (U1 snRNP) complex, a key spliceosome component. U1 snRNPs ensure the fidelity of RNA cotranscription and pre-mRNA splicing initiation, and their dysfunction has been implicated in neurodegenerative disorders and other age-related diseases.<br><br>MAIN BODY: This narrative review explores the impact of U1 snRNP dysregulation on retinal cells, focusing on its role in transcriptomic instability, impaired protein homeostasis, cellular stress, impaired autophagy, and inflammation, which are important features of AMD pathogenesis. Finally, we propose that targeting U1 snRNP dysfunction could provide a novel therapeutic approach to slow, prevent, or restore retinal degeneration, offering insights into broader implications for age-related diseases.<br><br>SHORT CONCLUSION: Understanding the molecular mechanisms underlying U1 snRNP dynamics in retinal health and degeneration is essential for developing innovative and effective treatments for AMD, which may provide ways to delay or reverse the effects of aging and associated diseases.},
}
@article {pmid41102554,
year = {2025},
author = {Zarranz-Ventura, J and Garay-Aramburu, G and Calvo, P and Zapata, MA and Arruabarrena, C and Arnáiz, P and García-Lunar, P and Sararols-Ramsay, L and , },
title = {Treatment intervals with first-generation anti-vascular endothelial growth factor drugs: evaluating the unmet need in a real-world neovascular age-related macular degeneration national database.},
journal = {Eye (London, England)},
volume = {39},
number = {18},
pages = {3306-3313},
pmid = {41102554},
issn = {1476-5454},
support = {Independent research collaboration//Roche (F. Hoffmann-La Roche Ltd)/ ; },
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Retrospective Studies ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Male ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Female ; Aged ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Visual Acuity/physiology ; Aged, 80 and over ; Databases, Factual ; Registries ; Follow-Up Studies ; Middle Aged ; },
abstract = {BACKGROUND: To evaluate treatment intervals at 12/24 months following initiation of anti-VEGF therapy and to characterise the clinical profile of neovascular AMD (nAMD) patients achieving extended treatment intervals (≥12 and ≥16 weeks).<br><br>METHODS: National, retrospective, real-world study using data from the validated web-based Fight Retinal Blindness (FRB!) registry. Treatment-naive nAMD eyes managed with approved first-generation intravitreal VEGF inhibitors (ranibizumab, aflibercept 2&#x2009;mg) and followed for at least 12 months were included. A subanalysis was conducted on eyes receiving a number of injections within range of a treat and extend (TAE) regimen at 12 and 24 months.<br><br>RESULTS: A total number of 1278/557 treatment-na&#xef;ve nAMD eyes within the TAE range category completed the required follow up at 12/24 months. At 12 months, 39.3% of eyes remained on &#x2264;Q8W, 22.5% >Q8W-&#x2009;<&#x2009;Q12W, 29.1% &#x2265;Q12W-&#x2009;<&#x2009;Q16 and 9.1% &#x2265;Q16W. At 24 months, the distribution was 35.4%, 17.6%, 28.3% and 18.7%, respectively. Mean VA change was not significantly different between groups at both 12 months (&#x2264;&#x2009;Q8W: +4.7, Q8-Q12: +3.5, Q12-Q16: +6.1, &#x2265;Q16W: +4.8 letters) and 24 months (&#x2264;Q8W: +5.8, Q8-Q12: +3.7, Q12-Q16: +4.1, &#x2265;Q16W: +3 letters). The percentage of visits with active lesions was similar across groups at both time points, indicating consistent disease control.<br><br>CONCLUSIONS: Despite receiving a number of injections within a TAE range, a substantial proportion of eyes failed to achieve extended treatment intervals at 12 and 24 months (61.8% and 52.9%, respectively). These results underscore the significant unmet therapeutic need in the management of nAMD with currently approved first-generation anti-VEGF agents.},
}
@article {pmid41102507,
year = {2025},
author = {Mauschitz, MM and Goerdt, L and Helbig, H and Holz, FG and Finger, RP and Brandl, C},
title = {[Nutrition and dietary supplements in age-related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {122},
number = {11},
pages = {873-879},
pmid = {41102507},
issn = {2731-7218},
mesh = {Humans ; *Macular Degeneration/epidemiology/prevention &amp; control/diet therapy ; *Dietary Supplements ; Micronutrients/administration &amp; dosage ; Diet, Mediterranean ; },
abstract = {BACKGROUND: Nutrition has an influence on the condition of our retina and appears to play a role in the complex, multifactorial pathogenesis of age-related macular degeneration (AMD).<br><br>OBJECTIVES: This article summarizes the current epidemiological evidence on nutrition and AMD and discusses the intake of specific nutrients as well as nutritional supplements and their potential role in prevention and disease modification.<br><br>MATERIAL AND METHODS: A&#xa0;narrative literature review of epidemiological studies, clinical trials and experimental work on the role of individual micronutrients, supplements and dietary patterns in AMD was carried out.<br><br>RESULTS: There is evidence of a&#xa0;protective effect for individual nutrients such as lutein, zeaxanthin, zinc and omega&#x2011;3 fatty acids. The AREDS studies in particular show a&#xa0;reduction in the progression of intermediate AMD to late stages through defined supplements. In addition, a&#xa0;Mediterranean diet correlates with a&#xa0;reduced risk of AMD. Nevertheless, the study results remain contradictory in some cases, which is due to methodological limitations and the complex pathogenesis of AMD.<br><br>DISCUSSION: Nutrition can potentially influence and reduce the risk for and progression of AMD. The existing literature underlines the potential of nutrition-based approaches, which must be further investigated in the future.},
}
@article {pmid41101497,
year = {2025},
author = {Broadhead, GK and Phan, L and Keenan, TDL and Chin, J and Hong, T and Chew, EY and Chang, AA},
title = {How to Judge Failure: Defining Treatment Resistance to Anti-VEGF Therapy in Exudative Maculopathies-A Systematic Scoping Review.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.10.006},
pmid = {41101497},
issn = {2468-6530},
abstract = {TOPIC: To evaluate the currently used definitions of treatment resistance in common retinal vascular diseases (neovascular age-related macular degeneration [nAMD], diabetic macular edema [DME], and retinal vein occlusion [RVO]) through a systematic scoping review of published studies.<br><br>CLINICAL RELEVANCE: A notable proportion of patients receiving therapy for retinal vascular diseases exhibit suboptimal responses to anti-VEGF therapy, however, currently there are no well-recognized definitions of resistance to treatment in these conditions. Clear definitions of treatment resistance would aid in developing treatment strategies and guiding research studies for these patients.<br><br>METHODS: The online databases PubMed, EMBASE, and the Cochrane Database of Systemic Reviews were searched on January 5, 2025, and August 16, 2025, for articles relating to treatment resistance in all 3 conditions.<br><br>RESULTS: In total, 402 publications were identified, of which 88 met the eligibility criteria: 30 relating to nAMD, 48 relating to DME, and 10 relating to RVO. Wide heterogeneity exists in the definition of treatment resistance for each condition. Persistent intraretinal fluid and/or subretinal fluid (SRF) on OCT is the most commonly used criterion in each condition. Duration of prior treatment for defining resistance is commonly longest for nAMD, however, treatment frequency of approximately &#x2264;6 weekly injections for defining resistance was generally similar across all 3 conditions.<br><br>CONCLUSION: There is wide variability in the definitions used, however, persistent intraretinal and/or SRF on OCT despite regular anti-VEGF therapy of approximately &#x2264;6 weekly intervals are the most common criteria across all 3 conditions. Adoption of these definitions for future studies would help ensure consistency and may potentially improve patient outcomes by improving the validity of future studies and allowing for the development of treatment paradigms to manage this patient subgroup.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41100220,
year = {2025},
author = {Palata Rezende, M and Faria, FA and Polido, J and Belfort, R and Cabral, T},
title = {Swept-Source OCT and OCT Angiography Biomarkers in Dry AMD Treated with Photobiomodulation: A Prospective Study.},
journal = {Photobiomodulation, photomedicine, and laser surgery},
volume = {},
number = {},
pages = {},
doi = {10.1177/25785478251385768},
pmid = {41100220},
issn = {2578-5478},
abstract = {Background: Photobiomodulation Valeda (PBM-Valeda) is a novel therapeutic approach for dry age-related macular degeneration (AMD). The primary objective of this short-term study was to conduct an analysis of best-corrected visual acuity (BCVA) and evaluate of biomarkers using state-of-the-art high-resolution imaging with swept-source optical coherence tomography OCT (SS-OCT) and OCT angiography (SS-OCTA) in dry AMD patients treated with PBM. Materials and Methods: This prospective, noncomparative, interventional case series pilot study examined the following biomarkers before and after PBM treatment: BCVA, central macular thickness (CMT), subfoveal choroidal thickness (SCT), capillary density (CD), avascular area of the superficial plexus (AASP), and avascular area of the deep plexus (AADP). All parameters were assessed at baseline and 1 week after treatment. A questionnaire (exploratory, not a validated endpoint) was carried out at the end of the treatment. Results: The study included 25 eyes (19 patients), predominantly in the Age-Related Eye Disease Study category II. A statistically significant change in BCVA was observed (p = 0.001). No statistically significant changes were observed in CMT, SCT, CD, AASP, or AADP (p > 0.05). The treatment was well tolerated, with few mild side effects, and no patient developed wet AMD. Conclusion: PBM-Valeda therapy demonstrated a favorable short-term safety profile in patients with dry AMD. The key finding of this study was the stability of SS-OCT and SS-OCTA biomarkers (CMT, SCT, CD, AASP, and AADP), with no adverse changes observed. These results reinforce the short-term safety of PBM. Reported side effects were minimal, with no evidence of retinotoxicity. This is the first prospective study to explore SS-OCT and SS-OCTA biomarkers in patients with dry AMD undergoing PBM therapy, providing preliminary safety data for future controlled trials.},
}
@article {pmid41099595,
year = {2025},
author = {Huang, L and Hu, P and Chen, J and Liu, J and Grzybowski, A},
title = {Smoking-Attributable Age-Related Macular Degeneration Vision Loss in China: 1990-2021 Trends and 2040 Projections.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {10},
pages = {21},
pmid = {41099595},
issn = {2164-2591},
mesh = {Humans ; China/epidemiology ; *Macular Degeneration/epidemiology/etiology ; Male ; Female ; *Smoking/adverse effects/epidemiology ; Aged ; Middle Aged ; Aged, 80 and over ; *Blindness/epidemiology/etiology ; },
abstract = {PURPOSE: This study aimed to analyze the spatiotemporal burden of vision loss due to age-related macular degeneration (AMD) attributable to smoking in China from 1990 to 2021, projecting to 2040.<br><br>METHODS: Based on the Global Burden of Diseases 2021 dataset, we quantified epidemiological metrics for AMD-related vision loss. Joinpoint regression identified trend turning points in the smoking-attributable AMD vision loss burden. The Autoregressive Integrated Moving Average model projected trajectories to 2040. Pearson correlation assessed associations between the Socio-demographic Index and burden indicators.<br><br>RESULTS: From 1990 to 2021, AMD-related vision loss cases surged approximately 200% (2021: 2,647,261 [95% uncertainty interval {UI}
: 2,185,651-3,258,896]), whereas Years Lived with Disability (YLDs) rose 184% to 153,220 (95% UI: 105,756-212,586). Age-standardized YLDs rates slightly declined by 2.74% to 7.25 per 100,000. The contribution of smoking to age-standardized YLDs decreased by 13.7%, declining from 16.82% (95% UI: 10.80%-22.44%) in 1990 to 14.52% (95% UI: 9.12%-19.58%) in 2021. Smoking-attributable AMD vision loss YLDs increased 133.5% to 23,157 cases, although age-standardized rate dropped to 1.05 per 100,000. The burden was 5.8 times higher in males than females. Joinpoint regression identified 1995 as a significant turning point for trend changes. Despite declining standardized rates, smoking-attributable AMD YLD cases are projected to increase by 38.5% by 2040 in male.<br><br>CONCLUSIONS: China's burden of smoking-attributable AMD vision loss exhibits male predominance and elderly clustering. Given the vast smoking population base and accelerating demographic ageing, this burden constitutes a major public health challenge.<br><br>TRANSLATIONAL RELEVANCE: The findings provide essential data for targeted interventions. We emphasize the crucial role of smoking cessation in AMD prevention and management.},
}
@article {pmid41098549,
year = {2025},
author = {Du, J and Chen, MY and Dasan, R and Chen, A and Kim, G and Naidu, A and Ebert, J and Huang, JM and Levinson, JD and Ali, MH and Do, BK},
title = {Comparison of Neovascular Age-Related Macular Degeneration Outcomes in Established vs New Patients of a Retina Practice.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251374576},
pmid = {41098549},
issn = {2474-1272},
abstract = {Purpose: To compare the treatment outcomes of newly diagnosed unilateral neovascular age-related macular degeneration (nAMD) in established patients of a retina practice with those of patients referred by non-retina specialist providers. Methods: This is a retrospective cohort study of patients with unilateral nAMD treated with intravitreal antivascular endothelial growth factor (anti-VEGF) therapy and at least 12 months of follow-up. Group 1 included established patients with initially bilateral dry age-related macular degeneration (AMD) that subsequently converted to unilateral nAMD requiring anti-VEGF treatment. Group 2 patients were referred to the practice with newly diagnosed unilateral nAMD requiring anti-VEGF treatment. All included patients presented with cases of new neovascular disease of the first eye. Results: There were 253 patients in Group 1 and 392 in Group 2. Average logMAR (Snellen equivalent) best-corrected visual acuity (BCVA) at time of neovascular conversion was 0.40 (20/50) for Group 1 and 0.62 (20/80) for Group 2 (P < .001). The percentage of patients with submacular hemorrhage was 7.9% for Group 1 and 18.6% for Group 2 (P < .001). By 12 months, BCVA improved to 0.36 (20/40) for Group 1 and 0.52 (20/60) for Group 2 (P < .001). The mean ± SD number of injections in the first 12 months of therapy was 8.64 ± 2.17 for Group 1 and 9.19 ± 2.33 for Group 2 (P = .003). Conclusions: Visual outcomes were superior in established patients of retina specialists at the time of nAMD conversion in the first eye. It may be advantageous for patients with dry AMD to already be under the care of a retina specialist at the time of neovascular conversion.},
}
@article {pmid41097011,
year = {2025},
author = {Campagnoli, LIM and Varesi, A and Fahmideh, F and Hakimizad, R and Petkovic, P and Barbieri, A and Marchesi, N and Pascale, A},
title = {From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41097011},
issn = {1422-0067},
mesh = {Humans ; *Metformin/therapeutic use/pharmacology ; *Hypoglycemic Agents/therapeutic use/pharmacology ; *Diabetes Mellitus, Type 2/drug therapy/metabolism ; Animals ; *Neurodegenerative Diseases/drug therapy/metabolism ; AMP-Activated Protein Kinases/metabolism ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; },
abstract = {Metformin, an oral antihyperglycemic drug, represents the cornerstone of pharmacological treatment for type 2 diabetes mellitus (T2DM). Its primary glucose-lowering effects are well established, predominantly mediated through the activation of AMP-activated protein kinase (AMPK). This activation leads to a reduction in hepatic glucose production (primarily by inhibiting gluconeogenesis and glycogenolysis) and an increase in peripheral glucose uptake and utilization. Beyond its direct impact on glucose metabolism, metformin also improves insulin sensitivity and has beneficial effects on lipid profiles. Increasingly, research shows that metformin has pleiotropic effects. In addition to its recognized antihyperglycemic action, metformin is emerging as a regulator of cellular processes implicated in aging. Indeed, emerging evidence suggests a potential role of metformin in modulating pathways associated with longevity and ameliorating the symptoms of age-related diseases, including neurodegenerative disorders (such as Alzheimer's and Parkinson's diseases), cardiovascular diseases, age-related macular degeneration, and osteoporosis. The proposed mechanisms for these broader effects involve AMPK activation, modulation of the mTOR pathway, reduction of oxidative stress, and promotion of autophagy. After exploring the established role of metformin in T2D, this review provides a comprehensive investigation of its promising applications in the context of age-related diseases, offering valuable insights into its multifaceted therapeutic potential beyond glycemic control.},
}
@article {pmid41096710,
year = {2025},
author = {Lazzeri, G and Ferrucci, M and Lenzi, P and Giambelluca, MA and Biagioni, F and Busceti, CL and Frati, A and Fornai, F},
title = {Modulation of mTOR Within Retinal Pigment Epithelium Affects Cell Viability and Mitochondrial Pathology.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41096710},
issn = {1422-0067},
support = {RC 2024-2025//Ministero della Salute/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *TOR Serine-Threonine Kinases/metabolism ; *Mitochondria/metabolism/drug effects/pathology/ultrastructure ; Humans ; Cell Survival/drug effects ; Sirolimus/pharmacology ; Autophagy/drug effects ; Curcumin/pharmacology ; Adenine/analogs &amp; derivatives/pharmacology ; Macular Degeneration/metabolism/pathology ; },
abstract = {The relevance of well-structured mitochondria in sustaining the integrity of the retinal pigment epithelium (RPE) is increasingly evident. Conversely, altered mitochondria are a culprit of age-related macular degeneration (AMD), which is influenced by the activity of mechanistic target of rapamycin (mTOR). In the present manuscript, the mitochondrial status of RPE cells was investigated by light and electron microscopy following the administration of various doses of compounds, which modulate mTOR. The study combines MitoTracker dyes and mitochondrial immunohistochemistry with in situ mitochondrial morphometry. Various doses of 3-methyladenine (3-MA), curcumin, and rapamycin were administered alone or in combination. The activity of autophagy and mTOR was quantified following each treatment. Administration of 3-MA led to activation of mTOR, which was associated with severe cell death, altered membrane permeability, and altered ZO-1 expression. In this condition, mitochondrial mass was reduced, despite a dramatic increase in damaged mitochondria being reported. The decrease in healthy mitochondria was concomitant with alterations in key mitochondria-related antigens such as Tomm20, Pink1, and Parkin. Specific mitochondrial alterations were quantified through in situ ultrastructural morphometry. Both curcumin and rapamycin counteract mTOR activation and rescue mitochondrial status, while preventing RPE cell loss and misplacement of decreased ZO-1 expression. Mitigation of mTOR may protect mitochondria in retinal degeneration.},
}
@article {pmid41095854,
year = {2025},
author = {Teper, S and Ledwoń, D and Romaniszyn-Kania, P and Sendecki, A and Tuszy, A and Nycz, J and Mitas, AW and Figurska, M and Wylęgała, E and Rękas, M},
title = {Twelve-Month Outcomes of Anti-VEGF Therapy for nAMD with Brolucizumab, Aflibercept, and Ranibizumab in the Polish National Registry: A Multicenter Database Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
pmid = {41095854},
issn = {2077-0383},
abstract = {Background/Objectives: Real-world registries of neovascular age-related macular degeneration (nAMD) treatments provide critical insights for optimizing patient care and resource allocation. This study evaluates one-year outcomes of anti-VEGF therapy with aflibercept, ranibizumab, and brolucizumab in the Polish Therapeutic Program Monitoring System between 1 January 2016 and 31 October 2023. Methods: We analyzed data from 51,902 treatment-naïve patients with nAMD, comparing baseline characteristics and outcomes across drugs, as well as between those who discontinued therapy early and those treated for at least one year. Results: No significant baseline differences were found between drug groups. One-year follow-up was available for 40,396 eyes; 3184 were lost to follow-up, and 8322 discontinued treatment: 14.4% for those receiving aflibercept, 24.1% for those receiving brolucizumab, and 20.1% for those receiving ranibizumab. Early discontinuers were older and had higher baseline visual acuity (aflibercept, ranibizumab). Twelve-month treatment outcomes, particularly visual acuity gains and injection frequency (~6-7/year), were similar across agents. Only ~22% achieved at least 0.3 logMAR improvement, underscoring real-world treatment challenges. Conclusions: System-level support, appropriate treatment intensification, and strategic use of newer, durable agents like brolucizumab are crucial to narrowing the gap between clinical trial efficacy and real-world effectiveness, ultimately improving long-term outcomes in nAMD care.},
}
@article {pmid41095792,
year = {2025},
author = {Chan, CC and Liu, PK and Cheng, KC and Lai, HC and Chang, YC},
title = {Efficacy and Safety of Intravitreal Faricimab in Age-Related Macular Degeneration-A Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
pmid = {41095792},
issn = {2077-0383},
abstract = {Neovascular age-related macular degeneration (nAMD) is a significant cause of vision loss globally, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents forming the cornerstone of treatment. Despite advances, the considerable treatment burden associated with frequent injections and the occurrence of suboptimal responses in some patients highlight an ongoing need for more effective and durable therapeutic options. Faricimab, a bispecific antibody that targets both VEGF-A and angiopoietin-2 (Ang-2), has been developed to address these challenges by promoting greater vascular stability and potentially offering extended treatment intervals. This review synthesizes current evidence from pivotal clinical trials (TENAYA/LUCERNE), real-world studies, meta-analyses, and case reports on the efficacy, durability, and safety of intravitreal faricimab for nAMD. Key efficacy outcomes, such as changes in best-corrected visual acuity and anatomical parameters (e.g., central subfield thickness, retinal fluid dynamics, pigment epithelial detachment morphology), are evaluated in both treatment-naïve and previously treated/treatment-resistant nAMD populations. The safety profile, including intraocular inflammation, retinal vasculitis, retinal pigment epithelium tears, and systemic adverse events, is also comprehensively addressed. Faricimab has demonstrated non-inferior visual outcomes compared to aflibercept 2 mg, alongside robust anatomical improvements and a significant potential for reduced treatment frequency, thereby lessening patient and healthcare system burden. While generally well-tolerated, ongoing monitoring for adverse events remains essential.},
}
@article {pmid41094968,
year = {2025},
author = {Sorgente, V and Correra, S and Verrillo, I and Cesarelli, M and Martinelli, F and Santone, A and Mercaldo, F},
title = {NeoNet: A Novel Deep Learning Model for Retinal Disease Diagnosis and Localization.},
journal = {Sensors (Basel, Switzerland)},
volume = {25},
number = {19},
pages = {},
pmid = {41094968},
issn = {1424-8220},
mesh = {*Deep Learning ; Humans ; Neural Networks, Computer ; *Retinal Diseases/diagnosis ; Diabetic Retinopathy/diagnosis/diagnostic imaging ; Retina/diagnostic imaging/pathology ; Macular Degeneration/diagnosis/diagnostic imaging ; Choroidal Neovascularization/diagnosis ; Algorithms ; },
abstract = {Retinal diseases are among the leading causes of vision impairment worldwide, and early detection is essential for enabling personalized treatments and preventing irreversible vision loss. In this paper, we propose a method aimed to identify and localize retinal conditions, i.e., Age-Related Macular Degeneration, Diabetic Retinopathy, and Choroidal Neovascularization, using explainable deep learning. For this purpose, we consider seven fine-tuned convolutional neural networks: MobileNet, LeNet, StandardCNN, CustomCNN, DenseNet, Inception, and EfficientNet. Moreover, we develop a novel architecture i.e., NeoNet, specifically designed for the detection of retinal diseases, achieving an accuracy of 99.5%. Furthermore, with the aim to provide explaianability behind the model decision, we highlight the most critical regions within retinal images influencing the predictions of the model. The obtained results show the ability of the model to detect pathological features, thereby supporting earlier and more accurate diagnosis of retinal diseases.},
}
@article {pmid41094548,
year = {2025},
author = {Carvalho, BFS and Rosa, AAM and Scherer, R and Nunes, VM and de Souza, FVM and da Silva, JLN and Neto, TDSR},
title = {Semantic segmentation of the avascular zone of the fovea in optical coherence tomography angiography: evaluation of techniques and applications in ocular diseases.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {109},
pmid = {41094548},
issn = {2056-9920},
abstract = {INTRODUCTION: This study addresses the use of zero-shot learning (ZSL) for segmentation of the foveal avascular zone (FAZ) in optical coherence tomography (OCT) images obtained through the RedCheck[®] platform. Accurate FAZ segmentation is essential for ophthalmologic diagnoses in conditions such as diabetic retinopathy and age-related macular degeneration. The proposed method aims to overcome the limitation of labeled data, reducing both the cost and time associated with model training.<br><br>METHODS: A total of 200 images from healthy patients were used. A neural network-based model was employed to identify the FAZ without specific labeled data, using pre-trained representations for contextual learning. Model performance was evaluated by comparing the automatic segmentation results with the manual annotations provided by specialists.<br><br>RESULTS: Quantitative analysis revealed a mean intersection over union (MIoU) of 0.86, indicating consistent model performance in identifying regions of interest. The median IoU was 0.89, with an interquartile range between 0.85 (Q1) and 0.92 (Q3), demonstrating the method&#x2019;s precision in most samples. Extreme values showed a maximum IOU of 0.97, reflecting excellent agreement, whereas the minimum IoU of 0.03 revealed limitations in atypical cases. The standard deviation of 0.11 indicated moderate variation in the results, and the 95% confidence interval for the MIoU ranged from 0.84 to 0.89, ensuring the statistical reliability of the approach.<br><br>DISCUSSION: The findings demonstrate the feasibility and accuracy of the ZSL-based method for FAZ segmentation, even in the absence of labeled data. Despite the positive results, variability observed in specific images highlights the need for improvements to increase the model&#x2019;s robustness in more heterogeneous data scenarios.},
}
@article {pmid41094540,
year = {2025},
author = {Shen, X and Chen, Y and He, B and Xi, R and Chen, J and Wu, Y},
title = {Ferrostatin-1, a ferroptosis inhibitor, mitigates all-trans-retinal-induced retinal pigment epithelium degeneration in mice.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1103},
pmid = {41094540},
issn = {1479-5876},
support = {82471093//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Ferroptosis/drug effects ; *Retinal Pigment Epithelium/pathology/drug effects ; *Cyclohexylamines/pharmacology/therapeutic use ; *Phenylenediamines/pharmacology/therapeutic use ; Reactive Oxygen Species/metabolism ; Mice ; *Retinaldehyde ; Lipid Peroxidation/drug effects ; *Retinal Degeneration/drug therapy/pathology/chemically induced ; Humans ; Cell Line ; Mitochondria/metabolism/drug effects ; Disease Models, Animal ; Macular Degeneration/pathology ; Cell Survival/drug effects ; Iron/metabolism ; ATP-Binding Cassette Transporters ; },
abstract = {BACKGROUND: Disruption of the retinoid (visual) cycle causes all-trans-retinal (atRAL) to accumulate in photoreceptors and retinal pigment epithelium (RPE), contributing to Stargardt disease type 1 (STGD1) and dry age-related macular degeneration (dAMD). Yet, the mechanisms underlying atRAL-induced RPE degeneration are not well understood. Here, we explored whether ferroptosis, a form of regulated cell death marked by iron-dependent lipid peroxidation, mediated RPE damage by atRAL.<br><br>METHODS: Cell and animal models of STGD1 and dAMD were established using ARPE-19 cells loaded with atRAL and Abca4[-/-]Rdh8[-/-] mice subjected to light exposure. Cell viability and morphology, mitochondrial morphology, ferrous iron (Fe[2+]) levels, reactive oxygen species (ROS) production, lipid peroxidation, and ferroptosis-related gene and protein expression were assessed using MTS assay, inverted and confocal microscopy, fluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting, respectively. The conditions of mouse retina were evaluated by electroretinography (ERG), optical coherence tomography (OCT), fundus imaging, and immunofluorescence labeling.<br><br>RESULTS: atRAL triggered ferroptosis of ARPE-19 cells through Fe[2+] accumulation, ROS generation, lipid peroxidation, mitochondrial damage, and abnormal expression of typical ferroptosis-related genes and proteins. These effects were capable of being alleviated by treatment with ferrostatin-1 (Fer-1), a potent ferroptosis inhibitor. Moreover, ferroptosis was clearly observed in the RPE of light-exposed Abca4[-/-]Rdh8[-/-] mice that showed rapid and excessive accumulation of atRAL in the retina. Notably, intraperitoneal administration of Fer-1 effectively mitigated the degeneration of the RPE and photoreceptors and significantly ameliorated retinal function in Abca4[-/-]Rdh8[-/-] mice following light exposure.<br><br>CONCLUSIONS: Ferroptosis plays a critical role in RPE damage by atRAL. Inhibition of ferroptosis by Fer-1 may enhance RPE cell survival and prevent subsequent photoreceptor degeneration in STGD1 and dAMD.},
}
@article {pmid41092158,
year = {2025},
author = {Ucak, T and Dedeli, FK and Kol, G and Uysal, B and Demir, ST},
title = {Optical Coherence Tomography &amp; Optical Coherence Tomography Angiography Biomarkers for Predicting Response to Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004702},
pmid = {41092158},
issn = {1539-2864},
abstract = {PURPOSE: To identify optical coherence tomography (OCT) and OCT angiography (OCTA) biomarkers associated with persistent retinal fluid in treatment-naïve neovascular age-related macular degeneration (nAMD) following three loading doses of anti-VEGF therapy.<br><br>METHODS: In this retrospective study, 60 treatment-na&#xef;ve typical nAMD patients received three monthly intravitreal bevacizumab injections. Four weeks after the third injection, patients were categorized as responders (Group 1, n = 30) if no fluid was seen, or as suboptimal responders (Group 2, n = 30) if fluid persisted. Baseline OCT and OCTA parameters were assessed, including central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED) height, hyperreflective foci (HF), subretinal hyperreflective material (SHRM), and macular neovascularization (MNV) morphology. OCTA features were analyzed for loop morphology, branching vessels, peripheral arcades, sea fan pattern, and hypointense halo. Vessel density (VD) was quantified in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC).<br><br>RESULTS: No significant differences were found between groups in baseline OCT parameters (all p > 0.05). VD in the SCP, DCP, and choriocapillaris did not differ between groups. However, OCTA revealed that loop morphology (p = 0.001), peripheral arcade (p = 0.009), and branching vessels (p = 0.032) were more frequent in suboptimal responders. On multivariate regression, only loop morphology remained a significant independent predictor of persistent fluid (OR = 4.36, p = 0.036).<br><br>CONCLUSIONS: Loop-shaped neovascular morphology on baseline OCTA independently predicted poor anatomical response to anti-VEGF therapy. Identifying such features may support early risk stratification and guide personalized treatment strategies.},
}
@article {pmid41091318,
year = {2025},
author = {Oshima, Y and Himeno, N and Nakamura, T and Ando, Y and Takaki, N and Hirata, M and Yamamoto, A},
title = {Treatment outcomes of patients with neovascular age-related macular degeneration after switching from aflibercept to faricimab.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41091318},
issn = {1613-2246},
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) can cause vision loss and irreversible blindness. However, its treatment needs to be improved. This study aimed to evaluate the 1-year treatment outcomes in patients with nAMD after switching from 2 mg aflibercept to faricimab.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: We included 83 eyes of 83 patients with nAMD who switched from 2 mg aflibercept to faricimab to extend the administration interval or eliminate exudative changes, with &#x2265; 1 year of follow-up. We retrospectively examined the 1-year treatment outcomes after switching, with the time of switching as the baseline.<br><br>RESULTS: After switching, the mean log minimum angle of resolution best corrected visual acuity was significantly improved from 0.35 to 0.33 (p = 0.0498), and the mean central retinal thickness was significantly reduced from 302 &#x3bc;m to 237 &#x3bc;m (p < 0.0001). A significant reduction was observed in the incidence of subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid (p < 0.05). The mean dosing interval was significantly extended from 5.58 weeks to 9.69 weeks (p < 0.0001). One year after switching, 66 eyes (80%) continued receiving faricimab, while 17 eyes (20%) were switched to other drugs owing to worsening exudation or other reasons.<br><br>CONCLUSION: One year after switching treatment for nAMD from 2 mg aflibercept to faricimab, visual acuity and macular morphology were improved, and the treatment interval was extended. The study's findings could help develop strategies for improving nAMD.},
}
@article {pmid41091136,
year = {2025},
author = {Sirks, MJ and van Dijk, EHC and Ghalayini, H and Bazdar, S and Yu, W and Yzer, S and Martinez Ciriano, JP and Schlingemann, RO and Diederen, RMH and Boon, CJF},
title = {Neovascular age-related macular degeneration without drusen.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70010},
pmid = {41091136},
issn = {1755-3768},
support = {//Mathilde Grant/ ; //Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; //Stichting Steunfonds Uitzicht/ ; //Stichting tot Verbetering van het Lot der Blinden/ ; //Stichting Leids Oogheelkundig Ondersteuningsfonds/ ; //Stichting voor Ooglijders/ ; //Rotterdamse Stichting Blindenbelangen/ ; //Stichting Blindenhulp/ ; },
abstract = {PURPOSE: To describe the clinical characteristics and 1-year follow-up of patients with neovascular AMD (nAMD) without drusen in either eye.<br><br>METHODS: This is a multicentre retrospective cohort study in three tertiary referral centres in The Netherlands. We included patients of 55&#x2009;years or older with nAMD in one or both eyes, without the presence of drusen or signs of another underlying disease in either eye. The medical charts and multimodal imaging (MMI) were evaluated by two independent graders. Eyes were divided into two groups: polypoidal choroidal vasculopathy (PCV)-associated macular neovascularization (MNV) and non-PCV MNV. We evaluated the visual acuity (VA) at baseline and 1&#x2009;year after baseline; complete resolution of macular fluid on optical coherence tomography (OCT) during 1&#x2009;year of follow-up; required treatments to achieve a complete resolution of macular fluid on OCT; complication rate.<br><br>RESULTS: We included 106 eyes of 99 patients, with a median age of 73&#x2009;years. Seventy-one eyes had PCV-associated MNV, and 35 eyes had non-PCV MNV. The overall median baseline VA was 0.22 logMAR (Snellen 20/30), and 0.15 logMAR (Snellen 20/28) at 1&#x2009;year follow-up. Subretinal haemorrhage was more common in PCV-associated MNV compared to non-PCV MNV, both at initial presentation (21% vs. 17%) and during the 1 year follow-up period (23% vs. 11%). In total, 31 out of 48 eyes (65%) achieved complete resolution of macular fluid on OCT during follow-up, most commonly achieved with combined photodynamic therapy (PDT)&#x2009;+&#x2009;intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections.<br><br>CONCLUSION: nAMD can occur without the presence of drusen in either eye. Treatment with anti-VEGF injections, PDT or a combination thereof appears to be effective, but more research is warranted.},
}
@article {pmid41089879,
year = {2025},
author = {Hejsek, L and Hrevuš, M and Burova, M and Beran, D and Cyžová, Z and Penčák, M and Pařilová, T and Liláková, D and Veith, M},
title = {Efficacy and Safety of Switching from Ranibizumab to Brolucizumab in Age-Related Macular Degeneration: Multicenter Real-World Outcomes.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3729-3740},
pmid = {41089879},
issn = {1177-5467},
abstract = {PURPOSE: To assess whether switching from ranibizumab (0.5 mg) to brolucizumab (6 mg) improves injection intervals, disease activity, and anatomical/functional outcomes in wet age-related macular degeneration (wAMD).<br><br>METHODS: This multicenter retrospective study included patients aged &#x2265;50 years with active wAMD, baseline visual acuity (VA) 35-70, lesion size &#x2264;8 disc areas, and submacular hemorrhage &#x2264;25%. All had prior ranibizumab and were switched to brolucizumab for suboptimal response. VA and central retinal thickness (CRT) were recorded at switch, 6, and 12 months. Injection counts before and after switching were analyzed. Safety was monitored for intraocular inflammation (IOI) and discontinuation.<br><br>RESULTS: Seventy-nine eyes (75 patients) were enrolled; 66 eyes (60 patients, median age 75.0 years [IQR: 70.0-80.0]) completed 12 months. Patients received median 12.0 ranibizumab injections [IQR: 8.0-19.0] pre-switch and 5.0 brolucizumab injections [IQR: 4.0-6.0] post-switch. Median switch VA was 50.0 letters [IQR: 36.5-63.0]; CRT was 319.0&#xa0;&#xb5;m [IQR: 258.0-393.0]. At 6 months, VA improved to 51.0 [IQR: 38.0-66.5] (p = 0.0001) and CRT decreased to 255.0&#xa0;&#xb5;m [IQR: 216.0-298.0] (p < 0.00000001). At 12 months VA was 50.5 [IQR: 38.5-68.0] (p = 0.0004 vs baseline) and CRT 251.5&#xa0;&#xb5;m [IQR: 207.5-282.5] (p < 0.0001). Adverse events included 6 IOI cases, with discontinuation in 9 eyes overall.<br><br>CONCLUSION: Switching to brolucizumab reduced CRT, modestly improved or stabilized VA, and decreased injection frequency with acceptable safety. Limitations include retrospective design, modest sample size, and exclusion of poor visual outcomes, potentially introducing selection bias.},
}
@article {pmid41087731,
year = {2025},
author = {Huang, J and McLean, GR and Franke, A},
title = {Twenty years of genome-wide association studies: Health translation challenges and AI opportunities.},
journal = {European journal of human genetics : EJHG},
volume = {33},
number = {12},
pages = {1579-1584},
pmid = {41087731},
issn = {1476-5438},
support = {82473740//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Genome-Wide Association Study/history/trends/methods ; Humans ; *Artificial Intelligence/trends ; *Translational Research, Biomedical/trends ; },
abstract = {A landmark genome-wide association study (GWAS) in 2005 led to a major discovery about the genetics of age-related macular degeneration. Since then, thousands of GWAS have been published and tens of thousands of genomic loci have been reported for association with human traits ranging from established ones (e.g. height, cardiovascular disease) to unconventional ones (e.g. same-sex sexual behavior, family income). While some claim that GWAS has already fulfilled its promises, we argue that it has yet to fully showcase its power in unraveling the secrets of the human genome and its links to phenotypes. The March 2025 bankruptcy of 23andMe serves as a stark reminder of the limited translational value of GWAS to the general public. The GWAS research community can achieve more only if we begin with a sober and objective assessment. Here, we first outline "Four Persistent Obstacles" that continue to hinder GWAS progress and discuss how a "Global Research Ecosystem" may be well-positioned to overcome them. We also highlight the transformative rise of artificial intelligence (AI) exemplified by AlphaFold's unprecedented power in predicting protein structures. Finally, we introduce a novel concept, the "trait efficiency locus (TEL)", as a complement to the widely used quantitative trait locus (QTL) framework, providing a new lens for evaluating genetic discoveries. One could also term it "structural trait locus (STL)", but "TEL" emphasizes the central idea that efficiency is what ultimately matters.},
}
@article {pmid41086904,
year = {2025},
author = {Sasaki, M and Apte, RS and Bastion, MC and Cheung, CY and Chakravarthy, U and Chang, A and Hwang, DK and Lai, CC and Lee, WK and Miyake, M and Raman, R and Sivaprasad, S and Spaide, RF and Tan, ACS and Tham, YC and Ruamviboonsuk, P and Yanagi, Y},
title = {International Consensus and Guidelines on Diagnosing and Managing Pachydrusen from APVRS, AEEC, APOIS, AAPPO, and ARI.},
journal = {American journal of ophthalmology},
volume = {281},
number = {},
pages = {573-589},
doi = {10.1016/j.ajo.2025.10.007},
pmid = {41086904},
issn = {1879-1891},
abstract = {PURPOSE: To establish evidence-based consensus statements on pachydrusen, a distinct drusen subtype associated with increased choroidal thickness, addressing current knowledge gaps in diagnosis, clinical significance, and management.<br><br>METHODS: An international expert panel systematically reviewed existing literature on pachydrusen characteristics, prevalence, and clinical associations. Consensus statements were developed through structured analysis of morphologic features, diagnostic criteria, and clinical outcomes across diverse populations.<br><br>RESULTS: Pachydrusen are morphologically distinct from soft drusen and subretinal drusenoid deposits, characterized by irregular, multilobulated yellow-white deposits &#x2265;125 &#x3bc;m with sharp borders. The genetic observations suggest that pachydrusen represent a distinct subtype within the age-related macular degeneration (AMD) spectrum. Prevalence varies markedly by ethnicity. Pachydrusen are frequently observed in eyes with polypoidal choroidal vasculopathy and type 1 macular neovascularization when exudation is present, although their presence is not consistently associated with an increased risk of exudative change and they rarely progress to geographic atrophy. They are associated with increased choroidal thickness and choroidal vascular alterations. Although multimodal imaging may provide additional insights into associated choroidal features, standardized criteria for color fundus photography-based identification are essential. The clinical significance regarding progression risk to late AMD needs further elucidation.<br><br>CONCLUSIONS: Pachydrusen are a distinct drusen subtype associated with generalized or localized choroidal thickening, but not necessarily with diffuse thickening. Recognition of pachydrusen highlights the importance of considering genetic background, ethnicity, and choroidal characteristics in AMD research and management.},
}
@article {pmid41086611,
year = {2025},
author = {Cukier, HN and DeRosa, BA and Coombs, LE and Tang, E and Leyva, DR and Lazzaro, AR and Gu, E and Dykxhoorn, DM and Haines, JL and Pericak-Vance, MA and Song, YE and Bush, WS and Griswold, AJ},
title = {Generation of two isogenic induced pluripotent stem cell lines derived from a Hispanic individual with Alzheimer's Disease and mosaic for loss of the Y chromosome.},
journal = {Stem cell research},
volume = {89},
number = {},
pages = {103851},
doi = {10.1016/j.scr.2025.103851},
pmid = {41086611},
issn = {1876-7753},
abstract = {Mosaic loss of the Y chromosome (LOY) is a somatic phenomenon that occurs in males as they age (Jacobs, 1963; Forsberg, 2017; Danielsson, 2020) and is associated with an elevated risk of developing numerous diseases, including Alzheimer's Disease (AD) (Dumanski, 2016; Palmer, et al., 2022; Garcia-Gonzalez, 2023), cancer (Holmes, 1985; Loftfield, 2018), diabetes (Loftfield, 2018), age related macular degeneration (Grassmann, 2019), and autoimmune disease (Persani, 2012; Lleo, 2013). The induced pluripotent cell lines (iPSCs) UMi050-A and UMi050-B were derived from a Hispanic male with loss of the Y chromosome in his blood and diagnosed with AD. This isogenic pair of lines with and without a Y chromosome is a unique resource to delve into the mechanism of LOY and its relationship to AD risk.},
}
@article {pmid41083560,
year = {2025},
author = {Alsamri, J and Alamgeer, M and Alqazzaz, A and Said, Y and Alshuhail, A and Alshammeri, M and Alkharashi, A and Alkhiri, H},
title = {Revolutionizing AMD detection Bi model CNNs and hybrid feature selection for automated grading.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35598},
pmid = {41083560},
issn = {2045-2322},
mesh = {*Macular Degeneration/diagnosis/diagnostic imaging ; Humans ; *Neural Networks, Computer ; Algorithms ; Fundus Oculi ; *Image Processing, Computer-Assisted/methods ; Deep Learning ; Aged ; Image Interpretation, Computer-Assisted/methods ; },
abstract = {Age-related macular degeneration (AMD) is a common cause of vision loss in older adults. The automated grading of AMD from fundus images can aid in early detection and treatment. In this research, we propose a comprehensive framework that can enhance the quality of fundus images and increase automated grading accuracy. We employ preprocessing techniques such as the Adaptive Contrast Enhancement Algorithm (CLAHE) and Gamma correction to improve image quality and feature representation. Additionally, we suggest a hybrid feature selection approach that combines handcrafted and deep learning-based features to identify discriminative features for AMD grading. This approach can comprehensively represent AMD-related abnormalities, leaving no room for ambiguity. Furthermore, we introduce a new Bi-Model Convolutional Neural Network (CNN) architecture that uses global and local features for accurate AMD grading. The Bi-Model CNN integrates feature representations extracted from the entire fundus image and local patches to capture global context and fine-grained details. This approach offers precise, consistent, and prompt results, thereby increasing the effectiveness of early disease identification. Experimental results demonstrate that the Bi-CNN + Feature Fusion model achieves a 99.5% accuracy, outperforming other configurations. The model's performance is further validated with high precision (0.995), recall (0.995), and F1-score (0.995), along with a Cohen's Kappa of 0.990, indicating almost perfect agreement between predicted and actual labels.},
}
@article {pmid41083247,
year = {2025},
author = {Britten-Jones, AC and Chen, FK and Mack, HG and Kolic, M and Hermawan, J and Hickey, DG and Edwards, TL and Ayton, LN and Guymer, RH and Abbott, CJ},
title = {Inherited Retinal Disease or Age-Related Macular Degeneration: Predictive Value of Genetic Testing in Macular Disease With Atypical Atrophy.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.70008},
pmid = {41083247},
issn = {1442-9071},
support = {//University of Melbourne/ ; //Macular Disease Foundation Australia Grant Family Fund/ ; GNT#1194667//National Health and Medical Research Council/ ; GNT#1195713//National Health and Medical Research Council/ ; },
abstract = {BACKGROUND: Both age-related macular degeneration (AMD) and inherited retinal disease (IRD) can present with outer retinal atrophy at the macula. Distinguishing between IRD and geographic atrophy (GA) secondary to AMD is important for appropriate management, particularly as disease-specific treatments become available. This study investigates the utility of genetic testing for suspected IRDs in individuals with atypical macular atrophy.<br><br>METHODS: Twenty-four participants aged over 50, presenting with macular atrophy atypical for AMD, underwent clinical assessments, multimodal retinal imaging and exome-based sequencing covering known IRD genes. Three retinal ophthalmologists reviewed genetic and clinical data to reach a consensus for the underlying cause of macular atrophy and identified a set of features that challenge an AMD diagnosis and suggest a higher likelihood of an IRD.<br><br>RESULTS: The panel judged 58% of atypical atrophy cases as likely being an IRD. Of these suspected cases, 57% (33% of the entire cohort) received IRD genetic confirmation (PRPH2, ABCA4 or MT-TL1 [m.3243A>G]-related IRD). The remaining cases were classified as GA (29%) or did not reach consensus on the likely diagnosis (13%). Clinical features aiding in the differentiation of IRD from GA included symptom onset before age 50, family history, distinctive autofluorescence patterns (speckled, reticular or widespread), extensive atrophy and absence of subretinal drusen.<br><br>CONCLUSION: IRD genetic testing is valuable if a positive identification is achieved, but negative results neither rule out IRD nor confirm AMD. Limitations in our ability to robustly differentiate IRD-related atrophy from GA, especially in advanced lesions, need further research to improve diagnostic accuracy.},
}
@article {pmid41082699,
year = {2025},
author = {Yeh, JH and Chang, YY and Chuang, CJ and Chen, TC and Tsou, SC and Huang, CJ and Hsieh, YH and Wang, I and Lee, MC and Lin, HW},
title = {Hesperidin and Hesperetin from Orange Peel Water Extract Protect against NaIO3-Induced Oxidative Damage in Retinal Pigment Epithelial Cells by Modulating PI3K/Akt/HIF-1α/BNIP3 Signaling.},
journal = {Journal of agricultural and food chemistry},
volume = {73},
number = {42},
pages = {26669-26682},
pmid = {41082699},
issn = {1520-5118},
mesh = {*Hesperidin/administration &amp; dosage ; *Oxidative Stress/drug effects ; Animals ; Proto-Oncogene Proteins c-akt/metabolism/genetics ; Mice ; Humans ; *Citrus sinensis/chemistry ; Phosphatidylinositol 3-Kinases/metabolism/genetics ; Signal Transduction/drug effects ; Iodates/adverse effects/toxicity ; *Plant Extracts/administration &amp; dosage ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; Membrane Proteins/metabolism/genetics ; Cell Line ; *Protective Agents/administration &amp; dosage ; Apoptosis/drug effects ; Epithelial Cells/drug effects/metabolism ; Male ; *Macular Degeneration/metabolism/genetics/drug therapy ; Mice, Inbred C57BL ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, with oxidative stress a major causative factor. Orange peel, rich in polyphenols and flavonoids, possesses potent antioxidant and anti-inflammatory activities. This study evaluated the protective effects of an ultrasound-assisted aqueous extract (OPWE) of orange peel and its major components, hesperidin and hesperetin, against sodium iodate (NaIO3)-induced retinal damage. Component identification was performed using 3D-HPLC and LC/MS, and the antioxidant capacity was determined using the DPPH and ABTS assays. In vitro, OPWE reduced oxidative stress, mitochondrial dysfunction, and apoptosis in NaIO3-treated ARPE-19 cells through the PI3K/Akt and HIF-1α/BNIP3 pathways. Notably, hesperetin exhibited comparable protective effects to OPWE, restoring cell viability and inhibiting ROS production. In vivo, oral administration of OPWE maintained retinal morphology and function in mice induced by NaIO3. These findings suggest that OPWE, especially hesperetin, is a promising natural candidate for preventing oxidative stress-related retinal degeneration and maintaining retinal health.},
}
@article {pmid41081949,
year = {2025},
author = {Zhou, Y and Wang, Z and Huang, C and Yu, X and Cai, X and Zhao, D and Cai, Y},
title = {Genetically predicted causal links between gut microbiota and biological aging phenotypes in age-related macular degeneration.},
journal = {Biogerontology},
volume = {26},
number = {6},
pages = {191},
pmid = {41081949},
issn = {1573-6768},
support = {2025M771943//China Postdoctoral Science Foundation/ ; 2024409//Shanghai Postdoctoral Excellence Program/ ; 202401056//Postdoctoral Initiative Fund of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Macular Degeneration/genetics/microbiology ; *Aging/genetics ; Phenotype ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Aged ; Male ; },
abstract = {Current knowledge regarding the role of gut microbiota (GM) dysbiosis and biological aging in the pathogenesis of age-related macular degeneration (AMD) remains limited. This study aims to explore the causal relationships among these factors in AMD development. Utilizing two-sample bidirectional mendelian randomization (MR), we analyzed genome-wide association study (GWAS) data from 105,248 individuals, including 14,034 early AMD cases, to assess causality between AMD, GM taxa, and biological aging phenotypes such as epigenetic clocks, telomere length, mitochondrial DNA copy number, immune cell traits, and inflammatory proteins. Multivariable MR (MVMR) was employed to evaluate mediation pathways, complemented by sensitivity analyses to ensure robustness. We identified 8 causal GM taxa (including one phylum, one class, one order, one family, and four species) along with 8 GM functional pathways. Additionally, 78 immune cell traits, 3 circulating inflammatory proteins, and DNA methylation PhenoAge acceleration were identified as causal biological aging phenotypes linked to AMD. Mediation analysis revealed three pathways connecting GM functional pathways, immune cell traits, and AMD. Reverse MR analysis highlighted the modifying effects of AMD on GM and other aging phenotypes. This study represents a pioneering effort to identify causal GM taxa associated with the onset of AMD and to unravel potential mechanisms from the perspective of biological aging, providing genetic insights into the connections among gut microbiota, immune cell traits, and AMD.},
}
@article {pmid41081892,
year = {2025},
author = {Schuhmayer, AC and Karl, NAM and Pomberger, L and Eidherr, M and Khalil, H and Kallab, M and Strohmaier, C and Bolz, M and Reisinger, A},
title = {Reduced ocular perfusion after intravitreal Aflibercept and faricimab: an exploratory study for Tie2 receptor distribution in ophthalmic capillaries.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41081892},
issn = {1435-702X},
abstract = {PURPOSE: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections reduce ocular perfusion in patients with neovascular age-related macular degeneration (nAMD). Faricimab blocks both, VEGF-A and Angiopoietin-2. The study investigated the effects of intravitreal Aflibercept or Faricimab on ocular perfusion in patients with nAMD.<br><br>METHODS: 36 eyes of 36 Caucasian patients with nAMD were initially enrolled and treated with either Aflibercept (n&#x2009;=&#x2009;18) or Faricimab (n&#x2009;=&#x2009;18). Two patients were excluded after screening failures, resulting in 34 eyes (n&#x2009;=&#x2009;17 per group) for analysis. Ocular perfusion was assessed using Laser Speckle Flowgraphy (LSFG) at baseline, and 1 and 4 weeks after the first injection. The main output parameter of LSFG, mean blur rate (MBR), was measured in the optic nerve head (ONH) and macula. MBR, defined by an ellipsoid region of interest (ROI), was calculated for the total ONH area (ONH-MA), major retinal vessels within the ONH (ONH-MV), and the tissue area containing microvasculature (ONH-MT). For macular measurements, a square ROI (150&#x2009;&#xd7;&#x2009;150 pixels) was placed temporal to the optic disc to measure choriocapillaris perfusion (CHOR) without including main retinal vessels.<br><br>RESULTS: Faricimab group showed a significant decrease in MV (p&#x2009;=&#x2009;0.006) after one week, while the decrease with Aflibercept was not significant after one week (p&#x2009;=&#x2009;0.29). After 4 weeks, both groups showed a significant decrease (p&#x2009;=&#x2009;0.003 and p&#x2009;=&#x2009;0.017, respectively). For MT and CHOR, both groups showed a significant decrease in perfusion, both after one and after 4 weeks (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Faricimab caused a more rapid decrease in retinal perfusion, while choroidal perfusion was equally reduced by Aflibercept and Faricimab. These different responses in the vascular systems seem to indicate a different distribution of Tie2 receptors for Angiopoietin-2. These findings warrant further investigation into the role of Tie2 receptors in the vascular response to anti-VEGF therapies.},
}
@article {pmid41081891,
year = {2025},
author = {Kataoka, K and Tanaka, K and Honjyo, J and Miyara, Y and Hashiya, N and Watanabe, Y and Yamamoto, A and Wakatsuki, Y and Nakai, A and Mukai, R and Kato, Y and Terao, N and Maehira, M and Maruko, I and Kawai, M and Iida, T and Koizumi, H and Sekiryu, T and Mori, R and Okada, AA and , },
title = {Treatment outcomes of switching to aflibercept 8 mg in previously-treated neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41081891},
issn = {1435-702X},
}
@article {pmid41080767,
year = {2025},
author = {Nemet, A and Anaki, L and Shitrit, IB and Wasser, LM and Plopsky, G and Beluga, S and Tuuminen, R},
title = {Advanced Age Does Not Predispose to Intraoperative Complications Among High-Risk Cataract Surgeries.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3713-3718},
pmid = {41080767},
issn = {1177-5467},
abstract = {BACKGROUND: To examine whether advanced age predisposes to intraoperative complications among cataract surgery cohort preoperatively stratified as high-risk.<br><br>METHODS: A retrospective analysis of 100 consecutive patients, 75 of which aged under 80 vs 25 of which aged 80 or above were analyzed for operation time, complication rates, postoperative best-corrected visual acuity (BCVA), and intraocular pressure. Secondary outcomes analysis focused on multivariable models on age and surgical outcomes adjusted for preoperative complication risk factors such as nuclear sclerosis severity, pseudoexfoliation, and intraoperative floppy iris syndrome (IFIS) and ocular comorbidities such as age-related macular degeneration and glaucoma.<br><br>RESULTS: Baseline variables for sex distribution, concomitant ocular and systemic comorbidities, nuclear sclerosis grade, pseudoexfoliation, BCVA, and IOP were comparable between the groups. None of the patients underwent anterior or posterior vitrectomy. No differences were observed in the rate of intraoperative floppy iris (IFIS) syndrome (17% vs 16%, P=1.000) and the use of surgical adjuncts such as iris hooks (1.3% vs 4.0%, P=0.439) between patients aged under 80 years and those 80 years or above. Postoperative BCVA at 1&#xa0;week (0.33&#xb1;0.35 LogMAR units vs 0.33&#xb1;0.29 LogMAR units, P=0.962) did not differ between those aged under 80 years and 80 years or above. For patient age at surgery, correlation analysis revealed no associations with operation time (B: -0.09; 95% CI: -0.44 to 0.27; P=0.628), surgical challenge rate (B: 1.12; 95% CI: 1.00 to 1.27; P=0.073), or postoperative BCVA at 1&#xa0;week (B: 0.004; 95% CI: -0.012 to 0.005; P=0.379). In multivariable analysis, patient age at surgery remained non-significant for operation time when adjusted for pseudoexfoliation and IFIS (B: -0.07, 95% CI: -0.43, 0.30; P=0.629). After adjustment for wet AMD and glaucoma, advancing age showed a trend towards worse 1-week postoperative BCVA, with each additional year corresponding to a 0.01 decline in LogMAR units (B: -0.01; 95% CI: -0.02, 0.00; P=0.051).<br><br>CONCLUSION: Advanced age should not be treated as an inherent risk factor or contraindication for cataract surgery in high-risk patients.},
}
@article {pmid41080270,
year = {2025},
author = {Vilkeviciute, A and Ciumbaraite, R and Pileckaite, E and Kriauciuniene, L and Hin Ma, H and Piskiniene, R and Liutkeviciene, R},
title = {Gender-Specific Associations of CYP4F2 (rs1558139) Gene Polymorphism and Serum Levels in Early and Exudative Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91988},
pmid = {41080270},
issn = {2168-8184},
abstract = {BACKGROUND: The study aimed to assess the potential association between CYP4F2 rs1558139 gene polymorphism, serum CYP4F2 levels, and the development of age-related macular degeneration (AMD).<br><br>MATERIALS AND METHODS: A total of 204 patients with early AMD, 204 patients with wet AMD, and 294 healthy individuals as controls participated in this study. Genotyping of rs1558139 was carried out using real-time polymerase chain reaction (RT-PCR), while levels of serum CYP4F2 protein were determined by enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: The allele A at CYP4F2 rs1558139 was statistically significantly less frequent in females with early AMD than in the control females (46.8% vs. 54.77%, p=0.037). However, in the exudative AMD group, the AA genotype was more frequent in women than in men (31.9% vs. 17.3%, p<0.001). Serum CYP4F2 concentration was higher in early and exudative AMD groups than in controls (5.394 (3.554) vs. 1.599 (4.142), p=0.013 and 8.422 (8.356) vs. 1.599 (4.142), p<0.001, respectively).<br><br>CONCLUSIONS: The&#xa0;CYP4F2 rs1558139 polymorphism shows gender-specific associations with AMD. The A allele is less frequent only in females with early AMD, while the AA genotype is more common in women with exudative AMD.&#xa0;A higher serum CYP4F2 level may contribute to the development of AMD.},
}
@article {pmid41077603,
year = {2025},
author = {Ye, L and Zhao, T and Tian, H and Li, R and Li, Z and Li, H and Liao, R and Chuan, J and Xu, H and Zou, L and Qu, C and Shi, Y and Yang, Z and Huang, L},
title = {Unveiling the choroidal immune landscape revealed interferon-gamma and TNF-alpha as novel therapeutic targets in dry AMD.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {41077603},
issn = {1869-1889},
abstract = {Age-related macular degeneration (AMD), particularly its atrophic (dry) form, is a leading cause of irreversible blindness in the elderly. Limited treatment efficacy stems from its complex pathogenesis, highlighting an urgent need for novel therapeutic targets. This study investigates the contribution of the choroidal immune microenvironment, focusing on intercellular communication involving resident fibroblasts-a cell type whose role in AMD remains poorly defined. By analyzing single-cell RNA sequencing data from human choroid, we interrogated crosstalk between fibroblasts, macrophages, and NK/T cells, identifying interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα) signaling pathways as central mediators. We demonstrate that activated choroidal fibroblasts release key inflammatory mediators, including IL6, CCL2, CSF1, CXCL9, and CXCL10, which functionally recruit macrophages and CD8[+] T cells, thereby shaping the local immune landscape. Critically, targeting these pathways in vivo using TAPI-1 (inhibiting TNFα processing) and Tofacitinib (inhibiting IFNγ signaling) significantly ameliorated retinal, RPE, and choroidal pathology in a NaIO3-induced murine model of dry AMD. Our findings underscore the pathogenic role of fibroblast-mediated choroidal inflammation driven by TNFα and IFNγ signaling in dry AMD, presenting these pathways as promising therapeutic targets.},
}
@article {pmid41077163,
year = {2025},
author = {Roskoski, R},
title = {Vascular endothelial cells and angiogenesis.},
journal = {Pharmacological research},
volume = {221},
number = {},
pages = {107983},
doi = {10.1016/j.phrs.2025.107983},
pmid = {41077163},
issn = {1096-1186},
mesh = {Humans ; Animals ; *Endothelial Cells/metabolism/physiology ; *Neovascularization, Pathologic/metabolism/drug therapy ; *Neovascularization, Physiologic ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Neoplasms/blood supply/drug therapy ; Signal Transduction ; Angiogenesis ; },
abstract = {Physiological vascular endothelial cell division and angiogenesis occur during embryonic development, wound healing, in the endometrium during the menstrual cycle, and during placental development. Otherwise, vascular endothelial cells divide less than once per decade. Neoplasms are limited in size (∼ 1.0 mm) owing to a deficiency of oxygen and metabolic fuels. To grow larger, new blood vessels form from pre-existing vasculature by angiogenesis (capillary sprouting). During this process, mature endothelial cells replicate and become incorporated into new capillaries resulting in tumor growth. Angiogenesis results in part from the increased production of vascular endothelial growth factors (VEGFs). The human VEGF family consists of VEGF-A/B/C/D and placental growth factor (PlGF). The VEGF family of receptors consists of three protein-tyrosine kinases (VEGFR1/2/3) and two nonprotein kinase receptors (neuropilin-1 and neuropilin-2). Semaphorins 3A-F/4A-G/5 A/B/6A-G/7 A are regulatory ligands that interact with their neuropilin and plexin receptors (PlxA1-A4/B1-B3/C1/D1) and regulate angiogenesis. Angiopoietin-1/2/4 interact with their Tie1/2 receptor protein-tyrosine kinases to modulate vasculogenesis and angiogenesis. Ephrin ligands (EfnA1/A2/A3/A4/A5/B1/B2/B3) and Ephrin receptors (EphA1/A2/A3/A4/A5/A6/A7/A8/A10/B1/B2/B3/B4/B6/) also contribute to angiogenesis. Platelet-derived growth factors, fibroblast growth factors, hepatocyte growth factor (c-Met), stem cell growth factor (Kit) receptor protein-tyrosine kinases, PKB/Akt, Src, and MAP kinases also participate in angiogenesis. Owing to its importance in tumor progression, the inhibition of angiogenic signaling represents an attractive cancer treatment. Ponatinib, regorafenib, and vandetanib are FDA-approved VEGFR, Tie2, and Ephrin receptor blockers used in the treatment of various malignancies. Other disorders characterized by aberrant angiogenesis include diabetic retinopathies and neovascular age-related macular degeneration.},
}
@article {pmid41076606,
year = {2025},
author = {Antal, R and Benyó, Z and Nagy, ZZ and Kovács, I and Fekete, JT and Győrffy, B and Kovács, KA},
title = {Recent advances in treating age-related macular degeneration and diabetic retinopathy: Current therapies and emerging novel approaches.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41076606},
issn = {2509-2723},
abstract = {The incidence of retinopathies is expected to increase globally as our population ages and diabetes becomes more prevalent. Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR) are major causes of severe vision loss. These ophthalmological conditions are associated with neovascularization caused by excessive vascular endothelial growth factor (VEGF) secretion. This review focuses on the milestones achieved during the last few decades in treating retinopathies, presents a meta-analysis of key human clinical trials, and finally describes various novel therapies, some of which could potentially eliminate the need for intravitreal injections of anti-VEGF in the future. According to data from clinical trials and everyday medical practice, treatments targeting VEGF are efficient; however, they can cause various systemic (such as stroke) and ocular adverse events. The most frequently experienced adverse reactions (such as endophthalmitis or retinal detachment) are related to the injection process itself. These complications warrant the efforts invested in developing novel approaches, including gene therapy-based products and inhibitors of VEGF receptors. We discuss here the strengths and drawbacks of gene therapy and highlight the potential of small-molecule tyrosine kinase inhibitors (TKIs) as alternative anti-neovascularization agents. TKIs have recently been tested via numerous administration routes, including simple oral dosing of oral formulations in addition to intravitreal implants, which allow for a slow release, intravitreal depots, and suprachoroidal injections. All of which have shown different safety and efficacy profiles. We conclude that gene therapy products, especially TKIs, have the potential to become inhibitors of ocular neovascularization in the upcoming years.},
}
@article {pmid41076458,
year = {2025},
author = {Khanani, AM and Bakri, SJ and Regillo, C and Weng, CY and Wong, TY and Baldwin, ME and Han, JJ and Leitch, IM},
title = {Novel targets beyond vascular endothelial growth factor-A inhibition: improving vision with neovascular age-related macular degeneration treatment.},
journal = {Eye (London, England)},
volume = {39},
number = {17},
pages = {3045-3057},
pmid = {41076458},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/physiopathology ; *Visual Acuity/physiology ; Receptors, Vascular Endothelial Growth Factor ; },
abstract = {The primary goal in the management of neovascular age-related macular degeneration (nAMD) is to optimise visual acuity outcomes for patients. Landmark clinical trials have demonstrated improved visual outcomes with standard-of-care vascular endothelial growth factor (VEGF) inhibitors, principally targeting a single ligand (VEGF-A). However, in the real-world setting, not all patients attain optimal visual outcomes with these monotherapies. The role of the VEGF-A and VEGF receptor (VEGFR)-2 axis in angiogenesis and vascular permeability is well characterised, but other VEGF family members, including VEGF-C and VEGF-D, which activate VEGFR-2 and VEGFR-3, have also been implicated in nAMD pathogenesis. This may explain the heterogeneous responses observed with current therapies that primarily inhibit VEGF-A signalling, and in patients who continue to lose vision despite treatment, the consequences can be profound. Vision loss affects daily living and can lead to increased cost of care and susceptibility to falls and injuries. This review will explore the VEGF family of ligands and receptors and their role in nAMD, as well as novel therapeutics in development that target mediators beyond VEGF-A with the potential to provide improved vision benefits to patients. In particular, sozinibercept, an investigational trap biologic inhibitor of VEGF-C and VEGF-D ligands, has shown promising efficacy with superior vision gains when used in combination with ranibizumab dosed monthly (standard-of-care therapy) vs. standard-of-care alone (i.e. monthly ranibizumab). This adds to the increasing evidence that multifaceted approaches that target the VEGF family beyond VEGF-A have the potential to provide better vision outcomes for patients with nAMD.},
}
@article {pmid41076031,
year = {2025},
author = {Seddon, JM and De, D and Rosner, B},
title = {Quantifying Effects Of Lifestyle Changes On Progression To Advanced Age-Related Macular Degeneration In High Genetic Risk Individuals.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2025.09.030},
pmid = {41076031},
issn = {1549-4713},
abstract = {PURPOSE: We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of affected patients.<br><br>DESIGN: Prospective longitudinal analysis PARTICIPANTS: Eyes with early/intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study severity scale. High genetic risk was defined as the third tertile of a genetic risk score (GRS) for progression, adjusted for age, race and sex.<br><br>METHODS: Information on lifestyle behaviors was obtained from baseline risk and food frequency questionnaires. Risk-inducing and health-promoting lifestyle profiles were defined based on dichotomous categorizations of smoking, body-mass index (BMI), and dietary caloric intake, green leafy vegetables and fish, in never and ever smokers. Cox proportional hazard ratios (HRs), relative risks and population attributable risks (PARs) were calculated, adjusting for inter-eye correlation, demographic factors, macular status and family history.<br><br>MAIN OUTCOME: Progression to advanced AMD (AAMD) and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years follow-up.<br><br>RESULTS: Among 898 high genetic risk eyes, 207 eyes progressed to AAMD (23%). Among never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting profile [HR = 3.3 (CI 1.8, 6.4), P <0.001]. In ever smokers, a high risk-inducing profile was independently associated with a 5-fold increased incidence of AAMD [HR = 5.3 (CI 2.3,11.9), P <0.001]. Stronger effects of lifestyle behaviors were seen for GA compared to NV. Estimated PARs suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers.<br><br>CONCLUSION: Unhealthy behaviors increased incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population, and 56-60% of AAMD incidence was attributed to modifiable factors: smoking, high BMI, high caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids. Results underscore the importance of lifestyle interventions in high genetic risk populations, such as relatives of affected patients and/or patients with a high GRS, to reduce progression from early/intermediate AMD to advanced vision-threatening stages.},
}
@article {pmid41075000,
year = {2025},
author = {Rodrigues Alves, N and Silva, PB and Barão, C and Costa, L and Donato, H and Basílio, A and Flores, R and Anjos, R},
title = {Ranibizumab biosimilars vs. reference Ranibizumab for neovascular age-related macular degeneration: a systematic review and meta-analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41075000},
issn = {1435-702X},
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss, with anti-vascular endothelial growth factor therapy being effective but costly. This systematic review and meta-analysis assessed the efficacy, safety, and immunogenicity of ranibizumab biosimilars versus ranibizumab in nAMD.<br><br>METHODS: We systematically searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing ranibizumab biosimilars with reference ranibizumab in nAMD. Outcomes included: (1) best-corrected visual acuity (BCVA), (2) proportion of patients losing fewer than 15 BCVA letters, (3) central subfield thickness (CST), (4) choroidal neovascularization (CNV) size, (5) safety outcomes, and (6) anti-drug antibodies (ADA). Data were pooled using a random-effects model, and heterogeneity assessed by I&#xb2;.<br><br>RESULTS: Ten RCTs (3704 eyes) were included, with 1944 (52.5%) receiving biosimilars. At short-term follow-up (8-16 weeks), biosimilars significantly improved BCVA over reference (MD -0.81 letters; 95% CI -1.41 to -0.21; p&#x2009;=&#x2009;0.008), although this difference is clinically negligible. At long-term follow-up (48-52 weeks), there was a non-significant trend toward greater BCVA improvement (MD -0.75 letters; 95% CI -1.62 to 0.12; p&#x2009;=&#x2009;0.09). The proportion losing fewer than 15 BCVA did not differ significantly (RR 0.99; 95% CI 0.98 to 1.00; p&#x2009;=&#x2009;0.21). CST changes were comparable. Notably, biosimilars reduced CNV size at long-term follow-up (MD -0.39&#xa0;mm&#xb2;; 95% CI -0.68 to -0.09; p&#x2009;=&#x2009;0.01). Safety outcomes and ADA incidence were similar between groups.<br><br>CONCLUSIONS: Ranibizumab biosimilars demonstrate comparable safety, immunogenicity, and efficacy to reference ranibizumab. The small short-term BCVA difference is not clinically meaningful, supporting biosimilars as cost-effective alternatives for nAMD.},
}
@article {pmid41072938,
year = {2025},
author = {Jaggi, D and Marugg, S and Berger, LE and Munk, MR and Zinkernagel, MS and Heussen, FM},
title = {Evaluating the risk of recurrence in neovascular age-related macular degeneration using OCT-angiography at the time of treatment exit.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327721},
pmid = {41072938},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: To find biomarkers on OCT-angiography (OCT-A) that indicate a higher risk of recurrence in neovascular age-related macular degeneration (nAMD) patients before anti-vascular endothelial growth factor (anti-VEGF) therapy termination.<br><br>METHODS: Retrospective, observational study. Stable, inactive nAMD patients who had been treated with a treat-and-extend regimen and met the predefined exit criteria were included. The macular neovascularisation (MNV) lesion was imaged on OCT-A. Lesion area, vessel density (VD), fractal dimension and height of feeder vessel were quantified. Patients with disease recurrence after termination were compared with those who stayed inactive.<br><br>RESULTS: Out of 819 eyes diagnosed with nAMD and 281 with a 2-year follow-up, 77 (27.4%) reached the exit criteria. Thirty-four eyes of 33 (15 female) patients with reliable OCT-A were further analysed. Mean age was 80.35 (&#xb1;9.29) years, the number of injections was 16.68 (&#xb1;8.22). Treatment duration before exit was 36.15 (&#xb1;16.63) months. After exit, 23 eyes stayed inactive for a follow-up period of 23.00 (&#xb1;16.18) months, and 11 experienced recurrence after 13.36 (&#xb1;9.90) months. VD was significantly higher in the recurrent versus inactive group with 0.60 (&#xb1;0.15) versus 0.47 (&#xb1;0.11), p=0.015. There was an insignificant tendency for the protective properties of type 1 MNV and a low feeder vessel.<br><br>CONCLUSION: OCT-A is useful in the risk calculation for recurrence in patients who are about to discontinue anti-VEGF treatments in nAMD. Patients with a high VD might need closer follow-ups or continued anti-VEGF treatments even if inactive.},
}
@article {pmid41072666,
year = {2025},
author = {Wang, R and Zhang, R and Zhou, J and Ran, J},
title = {Crosstalk between anti-angiogenic and pro-angiogenic pathways in disease: Mechanisms and therapeutic strategies.},
journal = {Pharmacology &amp; therapeutics},
volume = {276},
number = {},
pages = {108934},
doi = {10.1016/j.pharmthera.2025.108934},
pmid = {41072666},
issn = {1879-016X},
mesh = {Humans ; *Angiogenesis Inhibitors/pharmacology/therapeutic use ; *Neovascularization, Pathologic/drug therapy/metabolism ; Animals ; Neoplasms/drug therapy/blood supply ; Signal Transduction/drug effects ; *Angiogenesis Inducing Agents/pharmacology/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {Angiogenesis, which entails the sprouting of new blood vessels from existing ones, is a critical process in normal development and tissue repair. However, when dysregulated, it contributes to a variety of diseases, including cancer, ischemic disorders, and chronic inflammation. Central to these processes are key factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF). Recent research has focused on therapeutic modulation of angiogenesis, employing both anti-angiogenic and pro-angiogenic strategies to regulate these pathways. Anti-angiogenic therapies primarily target the VEGF pathway to inhibit vessel formation, thereby reducing tumor vascularization in cancer and preventing abnormal blood vessel growth in neovascular ocular diseases such as age-related macular degeneration and diabetic retinopathy. Conversely, pro-angiogenic therapies stimulate vessel growth to improve vascularization in conditions like coronary artery disease and Alzheimer's disease, enhancing tissue perfusion and promoting regeneration. In this review, we summarize current knowledge on targeted modulation of angiogenesis, detailing therapeutic strategies, the mechanisms that regulate vascular homeostasis, and their implications for disease management.},
}
@article {pmid41072536,
year = {2025},
author = {Liu, WW and Xu, ZJ and Xu, F},
title = {NEW INSIGHTS INTO THE PATHOGENESIS AND TREATMENT ADVANCES OF AGE - RELATED MACULAR DEGENERATION.},
journal = {Georgian medical news},
volume = {},
number = {364-365},
pages = {352-354},
pmid = {41072536},
issn = {1512-0112},
mesh = {Humans ; *Macular Degeneration/therapy/genetics/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/genetics ; Genetic Therapy ; Oxidative Stress ; Stem Cell Transplantation ; Lipid Metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent and vision - threatening disease among the elderly. This review article focuses on the latest understanding of its pathogenesis and the significant treatment advances. In terms of pathogenesis, new research reveals the complex interplay of genetic factors, such as complement pathway gene mutations, oxidative stress, chronic inflammation, and abnormal lipid metabolism in the development of AMD. The treatment landscape has also witnessed remarkable progress, with anti-vascular endothelial growth factor (VEGF) therapies revolutionizing the management of wet AMD, and emerging treatments like gene therapy, complement pathway inhibitors, and stem cell - based therapies showing great potential for both wet and dry AMD. This article aims to provide a comprehensive overview of these new insights and treatment options, which may contribute to better clinical management and future research directions for AMD.},
}
@article {pmid41072315,
year = {2025},
author = {Li, H and Yan, Y and Yan, H and Luo, Y and Wang, H and Zhao, L and Zang, R and Zeng, Q and Cui, T and Zhou, J and Ye, Z and Li, Z and Xi, J and Yue, W},
title = {Chronic low-dose cadmium exposure induces neurodevelopmental impairment in hESC-derived retinal organoids.},
journal = {Ecotoxicology and environmental safety},
volume = {305},
number = {},
pages = {119189},
doi = {10.1016/j.ecoenv.2025.119189},
pmid = {41072315},
issn = {1090-2414},
mesh = {Humans ; *Organoids/drug effects ; *Cadmium/toxicity ; *Retina/drug effects/embryology ; Cell Differentiation/drug effects ; Neurogenesis/drug effects ; Apoptosis/drug effects ; Dose-Response Relationship, Drug ; *Environmental Pollutants/toxicity ; Human Embryonic Stem Cells/drug effects ; },
abstract = {Cadmium, a heavy metal environmental toxin known for its neurotoxic effects on the central nervous system, is implicated in multiple eye diseases, including cataracts, glaucoma, and age-related macular degeneration. However, due to the lack of suitable experimental models, there is limited data on the impact of cadmium exposure on human retinal development. Human retinal organoids accurately mimic the 3D architecture of early fetal retinal tissue, making them suitable for investigating developmental retinal toxicity in the context of maternal cadmium exposure. This study found that cadmium exposure caused a dose- and time-dependent reduction in neural retina thickness and retinal organoid volume. And cadmium exposure specifically induced retinal cell apoptosis, inhibited retinal progenitor cell proliferation, and affected ganglion cell differentiation. After four weeks of cadmium exposure, retinal organoids exhibited abnormal cell distribution, disorganized neural retina structure, and generated rosette-like structures. Transcriptomic analysis revealed that cadmium exposure upregulated the expression of metallothioneins, profoundly disrupted ion homeostasis in retinal cells, and potentially suppressed the development of human retinal organoid by modulating pathways involved in environmental information processing. Overall, this study established a versatile and straightforward experimental model for assessing the influence of environmental toxic substances on human embryonic retinal development, and preliminarily elucidated the toxic effects and molecular mechanisms of long-term, low-dose cadmium exposure on the initial neurogenesis of the human retina.},
}
@article {pmid41071031,
year = {2025},
author = {Mizumoto, K and Kato, K and Matsubara, H and Matsui, Y and Chujo, S and Mase, Y and Muramoto, Y and Ikesugi, K and Kondo, M},
title = {Comparisons of Visibility of Two-Color (RG) to Three-Color (RGB) Ultra-Widefield Images for Ten Types of Fundus Lesions.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {10},
pages = {11},
pmid = {41071031},
issn = {2164-2591},
mesh = {Humans ; *Fundus Oculi ; *Retinal Diseases/diagnosis ; Female ; Male ; Middle Aged ; Aged ; },
abstract = {PURPOSE: To compare the visibility of fundus lesions between RGB and RG images obtained with an ultra-widefield (UWF) fundus imaging device (Optos) for 10 types of fundus lesions.<br><br>METHODS: UWF images from 30 patients representing 10 types of fundus lesions were analyzed: vessel sheathing, optic disc cupping, cotton wool spots, epiretinal membrane, laser photocoagulation scars, retinal drusen, retinal hemorrhage, retinal/choroidal detachment, chorioretinal atrophy, and macular degeneration. Three images of each type of lesion were used, and 26 board-certified ophthalmologists compared them. The raters compared the visibility of lesions on a five-point scale: RG significantly better = -2; RG slightly better = -1; equal = 0; RGB slightly better = +1; and RGB significantly better = +2. The Wilcoxon signed-rank test was used to determine the significance of the differences.<br><br>RESULTS: RGB images were rated significantly more visually favorable than the RG images for all 10 lesions (P < 0.01). The greatest improvements in perceived visibility in RGB images were observed for vessel sheathing (50.7%), optic disc cupping (49.8%), cotton wool spots (46.9%), and an epiretinal membrane (46.7%). Conversely, macular degeneration (22.7%) and chorioretinal atrophy (25.1%) had minimal advantages in RGB images.<br><br>CONCLUSIONS: RGB imaging improves the visibility of white and superficial fundus lesions but adds little benefit for deeper located lesions.<br><br>TRANSLATIONAL RELEVANCE: The results indicate that RGB imaging, which includes blue laser light, improves the visibility of superficial and white retinal lesions. These findings support the optimized use of color imaging modalities in clinical practice based on lesion characteristics.},
}
@article {pmid41070355,
year = {2025},
author = {Dodeller, F and Alliger, P and Heyn, J and Urosevic, D and Allmannsberger, L and Wersig, C and Silva, R},
title = {Development of Biosimilar Aflibercept SDZ-AFL.},
journal = {Current therapeutic research, clinical and experimental},
volume = {103},
number = {},
pages = {100812},
pmid = {41070355},
issn = {0011-393X},
abstract = {PURPOSE: Aflibercept is a recombinant fusion protein that binds with high affinity to vascular endothelial growth factor A (VEGF-A), and other growth factors, reducing pathological neovascularization and abnormal vascular permeability. Aflibercept is approved as a first-line treatment for several retinal diseases, including neovascular age-related macular degeneration (nAMD); however, the high costs of these biologic agents can impede patient access. In 2024, Sandoz biosimilar aflibercept (SDZ-AFL; SOK583A1, Enzeevu/Afqlir) was approved by the US Food and Drug Administration and the European Medicines Agency as a biosimilar of reference aflibercept (Ref-AFL; Eylea, a trademark of Bayer AG and in the US of Regeneron Pharmaceuticals, Inc) based on a comprehensive package of data.<br><br>METHODS: This narrative review summarizes the totality of evidence demonstrating biosimilarity between SDZ-AFL and Ref-AFL, including physicochemical and biological characterization data from analytical in vitro studies, results of an ocular pharmacokinetic (PK) study in rabbits, and clinical efficacy, safety, immunogenicity, and systemic PK data from Phase III clinical studies.<br><br>RESULTS: Analytical evaluation demonstrated that SDZ-AFL has structural homology with Ref-AFL, including identical amino acid sequences, indistinguishable higher-order structures, and highly similar levels of structural variants. SDZ-AFL and Ref-AFL also demonstrated highly similar in vitro biologic activities, including target binding affinity, and potency in terms of neutralization of VEGF-A. In a single-dose ocular PK study in rabbits, vitreal exposure was comparable between SDZ-AFL and Ref-AFL after intravitreal administration. A 52-week Phase III clinical study (Mylight) evaluated the efficacy, safety, immunogenicity, and systemic PK of SDZ-AFL and Ref-AFL in 484 participants with nAMD. The primary endpoint was mean change from baseline to week 8 in best corrected visual acuity (BCVA): the difference between the SDZ-AFL and Ref-AFL groups in this endpoint was -0.3 letters (90% CI -1.5 to 1.0), which met predefined bioequivalence margins. Secondary efficacy endpoints, including changes from baseline in BCVA and central subfield foveal thickness over the whole 52-week study, were also similar for SDZ-AFL and Ref-AFL. Two subsequent "in-use" studies confirmed the safe use of SDZ-AFL provided in either a vial kit or a prefilled syringe.<br><br>CONCLUSION: This comprehensive totality of evidence has established biosimilarity between SDZ-AFL and Ref-AFL based on comparable physicochemical and biological characteristics, as well as similarity in clinical efficacy, safety, and immunogenicity. The introduction of aflibercept biosimilars to the market is anticipated to reduce barriers to access, potentially increasing the number of appropriate patients with retinal diseases benefiting from this biologic therapy.},
}
@article {pmid41068986,
year = {2025},
author = {Wu, J and Jang, H and Kwak, H and Son, M and Jiang, W and Hwang, HY and Jo, DH and Kim, D and Kim, HH and Kim, JH},
title = {Engineered virus-like particle-assembled Vegfa-targeting Cas9 ribonucleoprotein treatment alleviates neovascularization in wet age-related macular degeneration.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {346},
pmid = {41068986},
issn = {1474-760X},
support = {2022M3A9F3017506//National Research Foundation of Korea/ ; 2022M3A9E4017127//National Research Foundation of Korea/ ; 202200004004//Kun-hee Lee Child Cancer &amp; Rare Disease Project/ ; 18-2023-0010//Seoul National University Hospital/ ; GTL24021-000//National Research Council of Science and Technology/ ; },
mesh = {Animals ; *Vascular Endothelial Growth Factor A/genetics/metabolism ; Mice ; Gene Editing/methods ; *Ribonucleoproteins/genetics ; *CRISPR-Associated Protein 9/genetics/metabolism ; *Choroidal Neovascularization/therapy/genetics ; CRISPR-Cas Systems ; NIH 3T3 Cells ; Disease Models, Animal ; Humans ; *Wet Macular Degeneration/therapy/genetics ; Genetic Therapy ; *Macular Degeneration/therapy/genetics ; },
abstract = {BACKGROUND: Age-related macular degeneration, particularly the wet form, is a leading cause of vision loss, characterized by vascular endothelial growth factor A (VEGFA) overproduction. Engineered virus-like particles (eVLPs) combine the efficiency of viral systems with the transient nature of non-viral platforms to offer a potential solution for delivering VEGFA-targeting genome editing enzymes in a safe and efficient manner. Here, we investigate the therapeutic efficacy of eVLPs for transient delivery of Vegfa-targeting Cas9 ribonucleoprotein in a laser-induced choroidal neovascularization mouse model of wet age-related macular degeneration.<br><br>RESULTS: We find that Cas9-eVLPs enables efficient intracellular delivery in vitro, achieving up to 99% insertion and deletion frequency at Vegfa target locus and significant VEGFA protein downregulation in NIH/3T3 cells. A single subretinal injection of Cas9-eVLPs into the mouse retinal pigment epithelium effectively disrupts Vegfa expression, achieving an average indel efficiency of 16.7%. Compared to control groups, the laser-induced choroidal neovascularization mouse model exhibits significantly reduced choroidal neovascularization formation following Cas9-eVLPs intervention, and decreased VEGFA protein levels are detected in the retinal pigment epithelium. Furthermore, the retinal anatomical and functional toxicity are not affected after treatment.<br><br>CONCLUSIONS: eVLPs exhibit the potential as a safe and efficient delivery platform for Cas9 ribonucleoproteins, achieving precise Vegfa downregulation and significant reduction in choroidal neovascularization in a mouse model of wet age-related macular degeneration. With transient delivery of gene editing enzymes, high editing efficiency, and minimal risk of genomic integration, eVLPs present a promising alternative to conventional delivery systems for advancing genome editing therapies in retinal diseases.},
}
@article {pmid41068150,
year = {2025},
author = {Terheyden, JH and Behning, C and Dunbar, HMP and Poor, S and Zakaria, N and Binns, AM and Saßmannshausen, M and Leal, S and Schmid, M and Holz, FG and Crabb, DP and Luhmann, UFO and Finger, RP and , },
title = {Patient-reported vision impairment in low luminance relates to visual function in age-related macular degeneration: A MACUSTAR study report.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {35223},
pmid = {41068150},
issn = {2045-2322},
mesh = {Humans ; *Macular Degeneration/physiopathology/complications ; Male ; Female ; Aged ; Visual Acuity/physiology ; Cross-Sectional Studies ; Aged, 80 and over ; *Vision Disorders/physiopathology/etiology ; Contrast Sensitivity/physiology ; Middle Aged ; Surveys and Questionnaires ; Patient Reported Outcome Measures ; },
abstract = {Early stages of age-related macular degeneration (AMD) can lead to a number of visual function deficits, but the patient relevance of these deficits is largely unknown. We therefore investigated how bilateral visual function domains affected by age-related macular degeneration (AMD) are associated with patient-reports. Using data from the cross-sectional part of the MACUSTAR study with 245 individuals with AMD (34 early AMD, 168 intermediate (i) AMD, 43 late AMD), the Vision Impairment in Low Luminance (VILL) questionnaire (subscales: reading, VILL_R; mobility, VILL_M; emotional well-being, VILL_E) and visual function assessments from both eyes (best-corrected and low-luminance visual acuity, BCVA, LLVA; Moorfields acuity, MA; contrast sensitivity, CS) were included. Associations between VILL and visual function data (better and worse eyes defined based on BCVA) were investigated using age- and sex-adjusted regression models. In the overall sample, VILL_R and VILL_M were associated with all functional tests across eyes (p ≤ 0.0389), while VILL_E was associated with MA and CS (p ≤ 0.0302). Regression estimates for BCVA, LLVA, MA and CS in the better-seeing eyes were -2.70, -1.84, -1.83 and 1.08 (VILL_R); -2.71, -1.87, -1.90 and 1.88 (VILL_M), and -0.25, -0.22, -2.15 and 1.57 (VILL_E). In iAMD, CS and MA in the worse-seeing eye were associated with two VILL subscales, respectively (VILL_R and VILL_M; VILL_M and VILL_E, respectively; p ≤ 0.0395), while BCVA and LLVA in the worse-seeing eye were both associated with one VILL subscale (VILL_M; p ≤ 0.0317). CS in the better eye was associated with VILL_M (p = 0.0454). Thus, patient-reported outcomes are associated with visual function assessments in both eyes in people with AMD. Contrast vision seems particularly patient-relevant in iAMD. Our results further support the construct validity of the VILL questionnaire.},
}
@article {pmid41067751,
year = {2025},
author = {Zeng, Y and Qiu, B and Chen, X and Zhang, X},
title = {OCT and OCTA quantitative metrics for polypoidal choroidal vasculopathy.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {41067751},
issn = {2397-3269},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply ; *Fluorescein Angiography/methods ; *Polyps/diagnosis ; *Choroidal Neovascularization/diagnosis ; *Choroid Diseases/diagnosis ; Polypoidal Choroidal Vasculopathy ; },
abstract = {Polypoidal choroidal vasculopathy (PCV) is characterised by distinctive polypoidal lesions, recurrent serosanguineous retinal pigment detachments and branched neovascular networks. The incidence of PCV is notably higher among Asian populations, leading to inferior clinical outcomes in the absence of intervention. The relationship between PCV and neovascular age-related macular degeneration remains a controversial. The advent of optical coherence tomography (OCT) and OCT angiography (OCTA) technologies has revolutionised our approach to understanding PCV pathogenesis. Innovative OCT and OCTA biomarkers, including double layer sign, the sign of polyps, vessel density, the diameter of choroidal vessels, choroidal vascularity index, and choroidal vortex have emerged as critical imaging parameters for elucidating the pathological intricacies of PCV. Quantitative analysis of the choroid has become an essential adjunct for investigating the mechanisms underlying PCV. This comprehensive review encapsulates the array of quantitative OCT and OCTA biomarkers vital for the diagnosis, prognosis, and clinical management of this complex ocular condition.},
}
@article {pmid41067369,
year = {2025},
author = {Le Du, J and Ronco, C},
title = {Therapeutic strategies targeting ocular vasculopathies: Current advances and emerging challenges.},
journal = {Drug discovery today},
volume = {30},
number = {11},
pages = {104496},
doi = {10.1016/j.drudis.2025.104496},
pmid = {41067369},
issn = {1878-5832},
mesh = {Humans ; Animals ; *Eye Diseases/drug therapy ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Genetic Therapy/methods ; },
abstract = {Ocular vasculopathies, including neovascular age-related macular degeneration (wet AMD), diabetic retinopathy, retinal vein occlusion, and radiation maculopathy, are major causes of vision loss driven by vascular endothelial growth factor (VEGF)-mediated neovascularization. Anti-VEGF therapies have transformed outcomes but face limitations from resistance, variable response, frequent injections, and adverse effects of broad VEGF blockade. This review discusses emerging approaches, including platelet-derived growth factor (PDGF), angiopoietin-2 (Ang-2), tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2), and integrin inhibitors, alongside innovations in long-acting biologics, gene therapy, and nanocarriers. Complementary strategies targeting alternative angiogenic pathways, inflammation, hypoxia, and neuroprotection might overcome resistance and preserve retinal function. Together, these advances highlight opportunities to optimize therapy and address unmet needs in ocular vasculopathies.},
}
@article {pmid41066402,
year = {2025},
author = {Pan, W and Man, REK and Fenwick, EK and Hu, Z and Jiang, Y and Tan, H and Chen, Z and Hoang, QV and Saw, SM and Lamoureux, EL and Lan, W and Yang, Z},
title = {A psychometric evaluation of the Chinese Impact of Vision Impairment (C-IVI) questionnaire in an adult cohort with high myopia using Rasch analysis.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0327708},
pmid = {41066402},
issn = {1932-6203},
mesh = {Humans ; Adult ; Male ; Female ; *Psychometrics/methods ; *Quality of Life ; Middle Aged ; Surveys and Questionnaires ; *Myopia/psychology ; *Vision Disorders/psychology ; Cohort Studies ; China ; Macular Degeneration/psychology ; Visual Acuity ; East Asian People ; },
abstract = {PURPOSE: A psychometric evaluation of the Chinese Impact of Vision Impairment (C-IVI) questionnaire in an adult cohort with high myopia using Rasch Analysis and determination of the relationship between vision-related quality-of-life (VRQoL) and myopia macular degeneration (MMD).<br><br>METHODS: We used the baseline visit data of the AIER-Singapore Eye Research Institute (SERI) High Myopia Adult Cohort Study. VRQoL was assessed using the 28-item C-IVI. Rasch analysis was conducted to evaluate the overall C-IVI and domain scores ('Mobility and independence'-MB, 'Reading and accessing information'-RD, and 'Emotional well-being'-EWB), including response category functioning, precision, unidimensionality, targeting, and differential item functioning (DIF). The criterion validity, C-IVI's ability to distinguish participants based on severity of vision impairment (VI), spherical equivalent (SER), and the presence of MMD were analyzed using ANOVA and pairwise t-tests.<br><br>RESULTS: There were 431 participants, with mean (SD) age of 42.2 (7.1) years, SER of -8.3 (3.8) D, and visual acuity of 0.1 (0.2) LogMAR. Of these, 15.8% presented MMD, 79.4%, 13.5%, 7.0%, and 0.2% had no, mild, moderate, and severe VI, respectively. Response thresholds were ordered for the overall and three domains. The overall range-based precision was 0.94, and 0.80 for each domain. The three domains demonstrated unidimensionality. DIF was uniform in overall and EWB, but not the MB and RD domains. Person estimates decreased with increasing VI severity, worsening SER, and presenting MMD (all p&#x2009;<&#x2009;0.05) for the overall and domain scores.<br><br>CONCLUSIONS: The C-IVI questionnaire is a valid and reliable tool for assessing VRQoL in adults with high myopia in China.},
}
@article {pmid41065791,
year = {2025},
author = {Chen, Y and Zhang, S and Zhong, Q and Chen, S and Ding, H and Ye, W and Zhang, K},
title = {Inflammatory Proteins Profiling in Tear Fluid in Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1177/10807683251384447},
pmid = {41065791},
issn = {1557-7732},
abstract = {Objective: To analyze the differential expression of inflammatory proteins in the tear fluid of patients with polypoidal choroidal vasculopathy (PCV) or neovascular age-related macular degeneration (nAMD). Methods: A total of 19 patients with PCV, 17 patients with nAMD, and 18 normal controls (NC) aged ≥50 years were enrolled. Tear samples were collected, and the expression levels of 92 inflammatory proteins were quantified using Olink technology. Differentially expressed proteins (DEPs) among the groups were analyzed, with particular attention to consistency with previous findings from aqueous humor studies. Results: Olink analysis revealed extensive DEPs among PCV, nAMD, and NC groups. Compared with NC, the PCV group exhibited significant upregulation of VEGFA, Interleukin (IL) -18, IL-1α, IL-8, IL-7, Monocyte chemotactic protein (MCP)-2, and Neurturin (NRTN), along with downregulation of Tumor necrosis factor (TNF) and IL-10. The nAMD group showed a more pronounced pro-inflammatory profile, with upregulation of VEGFA, IL-18, IL-8, IL-1α, IL-7, Fibroblast growth factor (FGF)-19, MCP-1, Matrix metalloproteinase (MMP)-10, NRTN, Stem cell factor (SCF), Osteoprotegerin (OPG), Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), MMP-1, MCP-2, Fms-related tyrosine kinase 3 ligand (Flt3L), Tumor Necrosis Factor - like Weak Inducer of Apoptosis (TWEAK), Caspase (CASP)-8, and Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and downregulation of IL-10 and IL-12β. Comparison between PCV and nAMD indicated that IL-12β and Hepatocyte growth factor (HGF) were specifically upregulated in PCV, whereas SCF, VEGFA, Flt3L, OPG, MCP-1, T-cell surface glycoprotein CD8α (CD8α), Cystatin D (CST5), MMP-1, TNFRSF9, Transforming growth factor-α (TGF-α), 4E-BP1, and CASP-8 were significantly downregulated in PCV relative to nAMD. Boxplot analysis confirmed that Flt3L, IL-18, IL-1α, IL-7, IL-8, MCP-1, MMP-1, OPG, SCF, and VEGFA were specifically elevated in nAMD compared with both PCV and NC groups, while IL-10 was specifically suppressed in PCV. Conclusions: Tear fluid analysis represents a feasible and noninvasive approach to investigate the pathogenesis of PCV and nAMD.},
}
@article {pmid41065753,
year = {2025},
author = {Tschulakow, AV and Xi, L and Schraermeyer, U and Julien, S},
title = {Pigment Epithelium-Derived Factor (PEDF)-Based Therapy Induced Photoreceptor Survival by Stabilizing Choroidal Neovessels in a VEGF Overexpression CNV Rat Model.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {19},
pages = {e71113},
pmid = {41065753},
issn = {1530-6860},
support = {//Dr. Werner Jackst&#xe4;dt-Stiftung/ ; BI 1551/3-1//Deutsche Forschungsgemeinschaft (DFG)/ ; },
mesh = {Animals ; *Serpins/pharmacology ; *Eye Proteins/pharmacology ; *Nerve Growth Factors/pharmacology ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Rats ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; Bevacizumab/pharmacology ; Disease Models, Animal ; Angiogenesis Inhibitors/pharmacology ; Male ; *Choroid/blood supply/metabolism/drug effects/pathology ; Intravitreal Injections ; Rats, Sprague-Dawley ; *Photoreceptor Cells, Vertebrate/drug effects ; },
abstract = {Pathological choroidal neovascularization (CNV), characterized by abnormal leaky vessel formation, can lead to vision impairment or blindness. Current standard treatment, anti-vascular endothelial growth factor (VEGF) therapy, while effective, can be associated with severe local and systemic side effects and resistance in some patients, necessitating novel therapeutic approaches. Evidence from wet age-related macular degeneration (AMD) donor eyes and patients suggests that functional, quiescent CNV can aid photoreceptor survival. Therefore, stabilizing functional neovessels rather than removing them could offer an effective alternative for treating pathological CNV. Pigment epithelium-derived factor (PEDF), a multifunctional protein with antiangiogenic, neuroprotective, and vessel-stabilizing properties, is a promising candidate for this approach. The efficacy of intravitreally injected PEDF protein, alone or in combination with bevacizumab, was investigated and compared to bevacizumab monotherapy in a VEGF overexpression-induced CNV rat model using in vivo imaging and histology. Following PEDF + bevacizumab treatment, a significant reduction in CNV thickness was observed, comparable to bevacizumab monotherapy. Notably, only PEDF and PEDF + bevacizumab treatments significantly preserved retinal thickness and enhanced photoreceptor survival at the CNV site. Ultrastructural analysis revealed that PEDF and PEDF + bevacizumab treatments increased CNV vessel lumina, stabilized these vessels by reducing the thickness of the extracellular matrix and refining its structure, and enhanced vessel fenestration and pericyte coverage, making PEDF-based therapy more effective than bevacizumab monotherapy. These findings suggest that supporting the maintenance of functional CNV vessels using PEDF may represent a novel and innovative strategy for the treatment of wet AMD.},
}
@article {pmid41064591,
year = {2025},
author = {Borsellino, PJ and Schauer, S and Rivas, A and Aharonian, K and Vida, TA},
title = {Filling in the Blind Spot: Integrating Charles Bonnet Syndrome Screening in Ophthalmology.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3619-3657},
pmid = {41064591},
issn = {1177-5467},
abstract = {PURPOSE: Charles Bonnet Syndrome (CBS) is an underdiagnosed condition affecting patients with significant vision loss who experience complex visual hallucinations while maintaining cognitive insight. This scoping review aims to synthesize existing literature on CBS prevalence, risk factors, and screening practices, and to propose a standardized, clinically implementable screening workflow for ophthalmologists.<br><br>PATIENTS AND METHODS: We conducted a structured literature search across four databases (PubMed, Embase, Web of Science, Scopus) using keywords related to CBS, visual impairment, screening, and diagnosis. Inclusion criteria encompassed peer-reviewed studies involving patients with vision loss that reported the use of screening tools, diagnostic criteria, or clinical assessments of CBS. Excluded were case reports with fewer than five patients, articles lacking full text or peer review, and those focused primarily on psychiatric or neurologic hallucinations. We identified 1,582 articles, with 89 studies meeting the final inclusion criteria.<br><br>RESULTS: CBS prevalence ranged from 2% to 30%, depending on the underlying ocular condition and screening method used. Age-related macular degeneration showed the highest association. Few studies utilized validated screening tools though the QR-SCB and NEVHI instruments demonstrated clinical utility. Barriers to diagnosis included patient reluctance to report symptoms and clinician unfamiliarity. We developed a pragmatic clinical model incorporating risk stratification, direct questioning, validated tools, and functional assessment to improve detection in ophthalmology clinics.<br><br>CONCLUSION: CBS remains underdiagnosed despite its significant psychosocial burden. A structured screening approach may increase diagnostic accuracy and support timely intervention. The proposed model offers ophthalmologists a practical pathway to integrate CBS assessment into routine care.},
}
@article {pmid41064534,
year = {2025},
author = {Hou, J and Guo, J and Shen, W and Xie, D and Li, P and Zhang, Y and Zhao, Z},
title = {Genetically Prioritized Plasma Proteins as Candidate Therapeutic Targets for Dry Age-Related Macular Degeneration.},
journal = {Journal of ophthalmology},
volume = {2025},
number = {},
pages = {3972293},
pmid = {41064534},
issn = {2090-004X},
abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, yet effective treatments remain limited. This study aimed to identify putative causal plasma proteins linked to dry AMD through proteome-wide Mendelian randomization (MR) and genetic pleiotropy analyses.<br><br>METHODS: We performed proteome-wide MR analyses using protein quantitative trait loci (pQTL) data from the UK Biobank Pharma Proteomics Project (UKB-PPP) and genetic summary statistics for dry AMD from FinnGen R11. Replication analyses were conducted using pQTL data from the deCODE Genetics cohort and dry AMD GWAS data from the Million Veteran Program (MVP), all in individuals of European ancestry. To enhance robustness, we conducted additional sensitivity analyses using colocalization and summary data-based MR (SMR) approaches. Cell-type-specific expression profiles derived from single-cell RNA sequencing (scRNA-seq) data were used to prioritize candidate drug targets based on tissue relevance and druggability.<br><br>RESULTS: Discovery MR analysis identified 22 plasma proteins putatively associated with dry AMD. Replication MR tests and genetic pleiotropy analyses prioritized 12 proteins. Two retinal cell-specific genes were validated through scRNA-seq analysis. Druggability assessment confirmed C3 as an established AMD target and identified MASP1 and CFHR2 as complement pathway components with partial druggability. Notably, the remaining nine proteins represent novel pathways in dry AMD pathogenesis, four of which offer immediate drug-repurposing opportunities with approved agents, while five represent previously unexplored therapeutic candidates with high mechanistic plausibility.<br><br>CONCLUSIONS: This study provides genetically supported therapeutic candidates for dry AMD and prioritizes candidates with high clinical potential, advancing therapeutic strategies for dry AMD.},
}
@article {pmid41063677,
year = {2025},
author = {Zhang, C and Zhang, W and Wang, T and Wen, L and Zhang, J},
title = {Polypoidal Choroidal Vasculopathy: From Clinicopathological and Molecular Perspectives.},
journal = {Ophthalmic research},
volume = {68},
number = {1},
pages = {1-16},
pmid = {41063677},
issn = {1423-0259},
abstract = {Polypoidal choroidal vasculopathy (PCV) causes a severe visual impairment in patients with neovascular age-related macular degeneration (nAMD). Currently, PCV is classified as a subtype or variant of type 1 macular neovascularization (MNV), based on the neovascular characteristics of the lesions. These include both polypoidal lesion(s) (PLs) and branching neovascular network (BNN) that develops within Bruch's membrane and is located beneath the basal lamina of the retinal pigment epithelium (RPE). Effective treatments for PCV remain limited, despite the variable efficacy of anti-vascular endothelial growth factor (VEGF) drugs in regressing PLs. A key contributing factor is the incomplete understanding of the disease mechanisms, which highlights the necessity for reliable animal models to facilitate further research. Thus, it is of great importance to comprehensively understand this complex disease from multiple perspectives, including clinical manifestations, multimodal imaging, and clinicopathological features. This study aims to elucidate the complexities of PCV through an integrated analysis of its clinical characteristics, pathological features, and molecular mechanisms. In fact, both PLs and BNN are the neovascular lesions as evidenced by both optical coherence tomography angiography (OCTA) and clinicopathological studies. However, several distinguishing features exist between PLs and BNN, including lesion location, cellular component, and vascular maturity. Three-dimensional OCTA reconstruction demonstrated the anteroposterior separation between the PLs and BNN, and the presence of the internal microvascular architecture with some small nodules within PLs. Importantly, the clinicopathological analysis demonstrated a marked incomplete coverage of mural cells, including no pericyte coverage in PLs and relatively less coverage of vascular smooth muscle cells in BNN based on the clinicopathological analysis. The incomplete coverage of mural cells might be due to the increased expression of angiopoietin 2 (Ang-2), resulting in the loss or dropout of mural cells via the integrin-mediated signaling pathway. Regressing PLs and promoting BNN maturity through various approaches might provide an optimal treatment strategy for PCV management. However, a comprehensive understanding of the complex mechanisms of PCV merits further investigation for better management of this refractory disease.},
}
@article {pmid41063197,
year = {2025},
author = {Reyes, AG and Shah, TJ and Linton, EF and Mortensen, ZQ and Boyce, TM and Ricca, AM and Coussa, RG and Boldt, HC and Folk, JC and Russell, SR and Han, IC and Gehrs, KM and Sohn, EH},
title = {Real-world short-term outcomes after switching to fixed-interval anti-VEGF therapy for neovascular AMD during the COVID-19 pandemic.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {103},
pmid = {41063197},
issn = {2056-9920},
support = {IK1RX005029//U.S. Department of Veterans Affairs/ ; R01-EY035435//National Eye Institute,United States/ ; },
abstract = {PURPOSE: To assess short-term real-world visual and anatomic outcomes in patients with neovascular age-related macular degeneration (nvAMD) following a protocol shift from an individualized treat-and-extend (T&amp;E) anti-VEGF regimen to a fixed-interval injection schedule without routine imaging during the early COVID-19 pandemic.<br><br>METHODS: This retrospective cohort study included patients with nvAMD undergoing anti-VEGF therapy at a single tertiary academic retina practice. In response to the COVID-19 pandemic, the clinic transitioned from a T&amp;E approach to a fixed 8-week injection schedule without routine OCT imaging between March 25 and July 1, 2020. Eyes with at least two visits and OCT imaging before and after the protocol change were included. Outcomes measured included visual acuity (VA), central macular thickness (CMT), fluid status, appointment adherence, COVID-19 cases, and mortality. Statistical comparisons were performed using paired t-tests and Wilcoxon signed-rank tests.<br><br>RESULTS: A total of 289 eyes (232 patients) were included. Mean VA before the switch was 20/45 (logMAR 0.35&#x2009;&#xb1;&#x2009;0.33) and 20/50 (logMAR 0.39&#x2009;&#xb1;&#x2009;0.33, p&#x2009;=&#x2009;0.17) after the switch. Mean CMT showed non-significant changes from 292.1&#x2009;&#xb1;&#x2009;89&#xa0;&#x3bc;m pre-switch to 298.7&#x2009;&#xb1;&#x2009;66&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.15) post-switch. COVID-19 affected 11 patients (6 deaths); no cases were linked to clinic visits, and staff remained unaffected.<br><br>CONCLUSIONS: Switching to fixed-interval injections with limited imaging effectively maintained visual and anatomical outcomes while safely reducing COVID-19 transmission risks. These results suggest that fixed-interval regimens may preserve short-term outcomes in established nvAMD patients and could be useful during future care disruptions or protocol changes.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40942-025-00734-w.},
}
@article {pmid41062838,
year = {2025},
author = {Doğan Arı, AB and Türkyılmaz, A and Kolkıran, A and Taşdelen, E and Kılıç, E},
title = {Ectodermal dysplasias and isolated ectodermal anomalies: expanding the clinical and molecular spectrum in a cohort of 36 patients.},
journal = {European journal of pediatrics},
volume = {184},
number = {11},
pages = {667},
pmid = {41062838},
issn = {1432-1076},
mesh = {Humans ; *Ectodermal Dysplasia/genetics/diagnosis ; Male ; Female ; Child ; Child, Preschool ; Infant ; Exome Sequencing ; Adolescent ; Genetic Association Studies ; Phenotype ; Mutation ; Edar Receptor/genetics ; Genetic Testing ; Ectodysplasins/genetics ; },
abstract = {UNLABELLED: Ectodermal dysplasias are clinically and genetically heterogeneous congenital disorders characterized by abnormal development of at least two of the four ectodermal tissues: teeth, hair, nails, and sweat glands. In this study, we summarized the clinical and molecular characteristics of the patients and contributed to the genotype-phenotype correlation. For genetic diagnosis, single-gene testing, clinical exome sequencing, whole-exome sequencing, and variant confirmation analyses were performed. In this study, 30 ectodermal dysplasia patients from 18 families and six patients with isolated ectodermal anomalies from three families were analyzed. A total of 21 unique variants were identified, five of which were novel. Of these, seven were classified as pathogenic, 11 as likely pathogenic, and three as variants of uncertain significance (LIPH, TSPEAR, HR). Hypohidrotic ectodermal dysplasia was the most frequently identified subtype, with variants in the EDAR gene found in 10 patients and in the EDA gene in seven patients. Two patients harbored WNT10A variants. Variants in the CDH3 gene were identified in six patients with macular degeneration. Additionally, variants in the LIPH and LPAR6 genes were detected in three patients presenting with woolly hair. In the remaining eight patients, variants were identified in the HR, TSPEAR, TP63, DSG1, and CST6 genes. Microcephaly was observed in 47% (8/17) of patients in the hypohidrotic ectodermal dysplasia group (EDA, EDAR) and in 66% (4/6) of patients carrying CDH3 variants. The patient with a TSPEAR variant also had Beckwith-Wiedemann syndrome.<br><br>CONCLUSION: Our clinical findings, together with the identification of novel variants in EDAR, LIPH, LPAR6, HR, and TP63, expand the clinical and molecular spectrum of ectodermal dysplasias. A potential association between microcephaly and ectodermal dysplasia is discussed. This study highlights the genetic heterogeneity of ectodermal dysplasias and emphasizes the importance of combining detailed clinical evaluation with molecular diagnostics.<br><br>WHAT IS KNOWN: &#x2022; Ectodermal dysplasias (EDs) are congenital disorders characterized by abnormal development of at least two of four ectodermal structures, such as hair, nails, teeth, and sweat glands. EDs represent a clinically and genetically heterogeneous group of disorders with over 200 distinct types described.<br><br>WHAT IS NEW: &#x2022; In the current study, we report the clinical and molecular genetic analysis of 36 patients and contribute to the genotype-phenotype correlation. Five novel variants were identified. Microcephaly was observed in 47% of patients in the hypohidrotic ectodermal dysplasia group and in 66% of patients carrying CDH3 variants. The patient with a TSPEAR variant also had Beckwith-Wiedemann syndrome.},
}
@article {pmid41062254,
year = {2025},
author = {Cozzi, M and Zweifel, S and Balaskas, K and Curcio, CA and Viola, F and Mehta, H and Zarranz-Ventura, J and Teo, KYC and O'Toole, L and Nolan, J and Green-Gomez, M and Johnson, EJ and Arnold, J and Staurenghi, G and Gillies, MC and Barthelmes, D and Invernizzi, A},
title = {Minimum set of outcome measures for non-advanced age-related macular degeneration: a Delphi consensus statement by the TRACER (intermediate age-related macular degeneration) study group.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327744},
pmid = {41062254},
issn = {1468-2079},
abstract = {BACKGROUND: The purpose of this study was to define a minimum set of outcome measures for patients affected by non-advanced age-related macular degeneration (AMD).<br><br>METHODS: A structured Delphi consensus process was conducted by a panel of worldwide experts in treatment outcome registries, imaging, nutrition and other AMD aspects. The experts answered anonymously to a series of surveys, each followed by a face-to-face meeting to discuss the pooled results. Supporting literature was shared among the group members by a facilitator before each round. Finally, all the results were discussed and the consensus document was created based on the level of agreement between experts.<br><br>RESULTS: Six rounds were conducted until a formal consensus was achieved. Five main sections were identified: demographic characteristics, health factors, functional, imaging and clinical outcomes. A minimum set of 28 outcome measures was subsequently developed and approved by all members. Based on the priority of various items, 24 fields were designated as mandatory, while the remaining were deemed optional. Five items are required only at baseline, 12 are to be assessed annually for changes and the remaining 0 1must be collected at each clinical assessment.<br><br>CONCLUSION: This newly defined minimum set of outcome measures for non-advanced AMD could be employed in future real-world data collection registries aimed at gathering comprehensive and longitudinally extensive clinical data on a global scale. This may help to elucidate the natural progression of non-advanced AMD and its response to new therapies.},
}
@article {pmid41062151,
year = {2025},
author = {Gismero Moreno, SM and Jódar Sánchez, F and García-Agua Soler, N and Rivas Ruiz, F and Garcia-Ruiz, AJ},
title = {Model-based pharmacoeconomic analysis of anti-VEGF strategies for neovascular age-related macular degeneration: a value-based comparison of real-world administration approaches.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e103539},
pmid = {41062151},
issn = {2044-6055},
mesh = {Humans ; Cost-Benefit Analysis ; Recombinant Fusion Proteins/economics/administration &amp; dosage/therapeutic use ; Ranibizumab/economics/administration &amp; dosage/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/economics/administration &amp; dosage/therapeutic use ; *Macular Degeneration/drug therapy/economics ; Models, Economic ; Economics, Pharmaceutical ; Spain ; Intravitreal Injections ; Antibodies, Monoclonal, Humanized/economics/administration &amp; dosage/therapeutic use ; },
abstract = {OBJECTIVES: To evaluate the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) using a value-based model that considers drug durability, dosing regimens and real-world administration strategies, including safe vial fractionation.<br><br>DESIGN AND SETTING: Model-based pharmacoeconomic analysis using data from randomised clinical trials and network meta-analyses. Analysis conducted from the payer perspective using cost data from the Spanish National Health System.<br><br>METHODS: A model-based analysis compared five anti-VEGF agents-innovator and biosimilar ranibizumab, aflibercept 2 mg, brolucizumab and faricimab-across three dosing regimens: fixed, Pro Re Nata and Treat-and-Extend (TAE). Administration formats included single-use vials, prefilled syringes and vial fractionation (VF), with or without dead-space-free (DSF) syringes to minimise waste. The primary outcome was cost per optimal responder, defined as a patient gaining &#x2265;15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, with and without adverse events. Cost-effectiveness was evaluated using Number Needed to Treat (NNT), Net Efficacy Adjusted for Risk-NNT (adjusted for safety) and incremental cost-effectiveness ratios. Secondary outcomes included the number of treated patients and optimal responders achievable within a fixed &#x20ac;1 000 000 budget.<br><br>RESULTS: The most cost-effective strategy was aflibercept 2&#x2009;mg under a TAE regimen using DSF VF, with a total cost of &#x20ac;6214 per patient and a cost per optimal responder of &#x20ac;27&#x2009;155. Under a fixed budget of &#x20ac;1&#x2009;000&#x2009;000, this approach allowed treatment of 160 patients, yielding 36 optimal responders. Faricimab with DSF VF ranked second, with a total cost of &#x20ac;5847 and a cost per optimal responder of &#x20ac;28&#x2009;652, treating 171 patients and achieving 34 responders. In contrast, single-use vials without VF led to substantially higher total costs (eg, &#x20ac;11&#x2009;305 for aflibercept TAE) and lower treatment capacity (eg, 88 patients treated).<br><br>CONCLUSIONS: This model demonstrates that combining durable agents, extended dosing intervals and optimised delivery strategies (eg, prefilled syringes and DSF VF) can substantially improve the cost-effectiveness and sustainability of anti-VEGF therapy in public health systems.},
}
@article {pmid41061823,
year = {2025},
author = {Tsai, HR and Chang, WC and Lee, YC},
title = {Oral Acetylcysteine and the Risk of Age-Related Macular Degeneration: A Retrospective Cohort Study.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2025.09.025},
pmid = {41061823},
issn = {1549-4713},
abstract = {PURPOSE: N-acetylcysteine (NAC) functions as both a direct antioxidant agent and precursor for glutathione (GSH) synthesis, both of which are implicated in the pathogenesis of age-related macular degeneration (AMD). However, whether NAC use confers protective effects against AMD remains unclear. This study aimed to investigate potential associations between NAC use and the risks of AMD development in a large cohort of the Taiwanese population.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: The study included 22 498 NAC users and 138 607 non-NAC users between 2003 and 2017 before propensity score matching (PSM).<br><br>METHODS: This nationwide, population-based study leveraged data from the Taiwan National Health Insurance Research Database. Propensity score matching was applied to ensure comparability of baseline demographics and comorbidities between NAC users and nonusers. Stratified analyses by age and sex were conducted, and a cumulative defined daily dose was calculated to evaluate dose-response relationships among NAC users. Cox proportional hazards regression models were used post-PSM to estimate the hazard ratio (HR) for each outcome.<br><br>MAIN OUTCOME MEASURES: Outcome measures included the HR of overall, dry, and wet AMD.<br><br>RESULTS: After PSM, 5234 patients were included in each cohort: NAC users and non-NAC users. N-acetylcysteine users exhibited a significantly lower risk of AMD than nonusers did (HR, 0.19; 95% confidence interval [CI], 0.14-0.26; P < 0.001). This protective effect was observed for both dry AMD (HR, 0.19; 95% CI, 0.14-0.26) and wet AMD (HR, 0.31; 95% CI, 0.12-0.81). Stratified analyses demonstrated a reduced risk of AMD among NAC users, consistent across different age and sex groups. A dose-response relationship was identified, with higher cumulative doses of NAC associated with greater reductions in the risk of AMD and dry AMD. Sensitivity analyses for patients aged &#x2265;60 and &#x2265;70 years further supported the association between NAC use and reduced AMD risk, particularly for dry AMD.<br><br>CONCLUSIONS: Use of NAC was associated with a significantly reduced risk of AMD, especially dry AMD. These findings support the need for further investigation into the effectiveness of NAC as a preventive treatment for AMD.<br><br>FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid41061694,
year = {2025},
author = {Shah, N and Tran, E and Aly, M and Phu, V and Laughlin, E and Malvankar-Mehta, MS},
title = {Depression and Anxiety in Patients With Irreversible Vision Loss: Meta-Analysis and Systematic Review.},
journal = {International journal of psychiatry in medicine},
volume = {},
number = {},
pages = {912174251382653},
doi = {10.1177/00912174251382653},
pmid = {41061694},
issn = {1541-3527},
abstract = {ObjectiveApproximately 295 million individuals globally live with moderate to severe irreversible vision loss, primarily due to conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). Vision impairment diminishes quality of life leading to higher rates of depression and anxiety. This study investigated the prevalence of anxiety and depression in patients with irreversible vision loss, with a comparative analysis across the conditions of AMD, diabetic retinopathy, and glaucoma.MethodsA comprehensive literature search was conducted in Medline, Embase, CINAHL, and Cochrane databases, supplemented by manual searches of conference literature.ResultsThe prevalence of depression in patients with irreversible vision loss was found to be 21% (95% CI: 0.17-0.26) among 76 561 patients, with variations based on the cause: 27% (95% CI: 0.19-0.35) in AMD, 48% (95% CI: 0.32-0.64) in diabetic retinopathy, and 23% (95% CI: 0.16-0.29) in glaucoma. Anxiety prevalence was 22% (95% CI: 0.15-0.30) among 25 616 patients.ConclusionThe high prevalence of depression and anxiety underscores the need for comprehensive healthcare approaches that incorporate mental health support, including vision rehabilitation, psychotherapy, pharmacological interventions, and lifestyle modifications. Future research should explore factors that protect against anxiety and depression, as well as address the long-term effects of vision loss treatments on mental health outcomes.},
}
@article {pmid41061005,
year = {2025},
author = {Agius, D and Mamo, J and Calleja, N and Cassar, D and Marku, X and Nappa, MC and Zammit, M and Pace, ME and Carbonaro, F},
title = {The population characteristics and prevalence of visual impairment in a Southern European population.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251383740},
doi = {10.1177/11206721251383740},
pmid = {41061005},
issn = {1724-6016},
abstract = {PurposeTo describe the population characteristics, prevalence, and causes of visual impairment in Maltese adults aged 50-80 years.MethodsThe Malta Eye Study invited 4,006 random adults aged 50-80 for eye exams and interviews at the Malta and Gozo state hospitals (September 2021-July 2024). Tests included visual acuity, refraction, anthropometry, clinical measurements, tonometry, slit-lamp and dilated fundus exams, retinal imaging, and cognitive screening. Interviews covered sociodemographic, medical, ocular, and medication histories.ResultsA representative sample of 1,794 individuals (44.8% turnout) were assessed. Visual impairment in either eye was found in 23.9% (95%CI 21.9%-25.9%), and bilateral impairment in 6.0% (95%CI 4.9%-7.2%). The most common causes in either eye were uncorrected/undercorrected refractive error (12.3%), amblyopia (5.0%), cataract (3.8%), pathological myopia (1.3%), diabetic retinopathy (0.8%), age-related macular degeneration (0.6%), and glaucoma (0.4%). Predictors of visual impairment included older age, lower education, diabetes requiring insulin and tablets, and dementia. Protective factors were sunglasses use and angiotensin receptor blocker therapy.ConclusionsAlthough overall visual impairment rates are favourable, this study highlights the need to strengthen screening and treatment services for avoidable causes, particularly by improving public optometry access, among older adults, socioeconomically vulnerable groups, and those with poorly controlled diabetes.},
}
@article {pmid41060759,
year = {2025},
author = {Sotani, N and Kusuhara, S and Nishisho, R and Kuno, H and Shima, H and Haruwaka, K and Mori, Y and Kishi, M and Furuyashiki, T and Kobayashi, K and Wake, H and Takumi, T and Nakamura, M and Tachibana, Y},
title = {Transpupillary in vivo two-photon imaging reveals enhanced surveillance of retinal microglia in diabetic mice.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {41},
pages = {e2426241122},
pmid = {41060759},
issn = {1091-6490},
support = {JPMJMS239F//MEXT | Japan Science and Technology Agency (JST)/ ; JPMJMS2299//Japan Agency for Medical Research and Development (AMED)/ ; 22K19732 and 24K02339//Japan Society for the Promotion of Science London (JSPS)/ ; 15K10865 18K09409 21K09698//Japan Society for the Promotion of Science London (JSPS)/ ; 24K22086//Japan Society for the Promotion of Science London (JSPS)/ ; 21H04812 and 24K22086//Japan Society for the Promotion of Science London (JSPS)/ ; },
mesh = {Animals ; *Microglia/pathology/metabolism/drug effects ; Mice ; *Retina/diagnostic imaging/pathology ; *Diabetic Retinopathy/pathology/diagnostic imaging ; *Diabetes Mellitus, Experimental/pathology ; *Microscopy, Fluorescence, Multiphoton/methods ; Mice, Inbred C57BL ; Retinal Vessels ; },
abstract = {The retina, located outside the cranium, serves as an ideal structure for investigating information processing within the central nervous system due to its well-organized neurovascular unit comprising diverse cell types, including neurons, glial cells (such as microglia, Müller glia, and astrocytes), pericytes, and vascular endothelial cells. Disrupted retinal homeostasis contributes to various ocular diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinitis pigmentosa. However, noninvasive in vivo imaging methods to study the pathogenesis of these disorders remain limited. Here, we developed a two-photon microscopy technique for real-time, transpupillary in vivo visualization of the retinal neurovascular unit in mice. Our approach integrates systematic head fixation, a custom-made polymethyl methacrylate contact lens, and a glycerin immersion objective lens with an extended working distance and a higher numerical aperture, specifically designed for two-photon microscopy. This method enabled us to visualize dynamic microglial process activity around retinal blood vessels. Our results revealed that retinal microglia exhibit enhanced surveillance under diabetic conditions, which is undetectable by static confocal microscopy. Furthermore, we demonstrated that liraglutide, a glucagon-like peptide-1 receptor agonist commonly used for the treatment of diabetes and obesity, reversed the enhanced microglial behaviors in the diabetic retina. Our simple yet effective approach mitigates the need for advanced optical systems like adaptive optics, providing an effective tool for real-time imaging of the retina. This method offers a valuable resource for visual neuroscience research and holds great potential for clinical applications, particularly in the early diagnosis, intervention, and monitoring of retinal diseases.},
}
@article {pmid41060147,
year = {2025},
author = {Molbech, CR and Bøegh, MM and Nielsen, MK and Subhi, Y and Liisborg, C and Roubeix, C and Sennlaub, F and Mehlsen, J and Sørensen, TL},
title = {Impaired Vagal Tone Function-Based Regulation of Systemic Inflammation in Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {13},
pages = {16},
pmid = {41060147},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Prospective Studies ; *Vagus Nerve/physiopathology/physiology ; Aged ; Heart Rate/physiology ; Case-Control Studies ; *Inflammation/physiopathology ; *Wet Macular Degeneration/physiopathology/immunology ; T-Lymphocytes, Regulatory/immunology ; Middle Aged ; Aged, 80 and over ; CD4-Positive T-Lymphocytes/immunology ; },
abstract = {PURPOSE: The purpose of this study was to investigate vagal nerve function and correlation to CD4+ T-cell population in patients with neovascular age-related macular degeneration (nvAMD) and healthy individuals.<br><br>METHODS: This study is a prospective case-control study including 36 patients with nvAMD and 40 healthy individuals. We measured the proxy of vagus nerve activity, the resting heart rate variability (HRV). Freshly sampled venous blood was prepared to measure CD4+ T-cell populations regulated by the vagal tone (regulatory T cells [Tregs], recently thymic emigrant Tregs, na&#xef;ve Tregs, and effector memory T cells).<br><br>RESULTS: Compared with healthy individuals, patients with nvAMD had significantly lower HRV (low frequency/high frequency [LF/HR] ratio, P = 0.037 and standard deviation [SD] ratio, P = 0.011), indicating impaired vagal function. HRV measures negatively correlated to the proportion of Tregs (square root of the mean squared difference of successive NN intervals [RMSSD], P = 0.046) and memory T cells (RMSSD, P = 0.046) in healthy individuals, suggesting an intact regulatory capacity. These correlations were not found in patients with neovascular AMD, suggesting an impaired vagus nerve-regulatory T cell axis. Patients with nvAMD had significantly higher Tregs (P = 0.0005), na&#xef;ve Tregs (P = 0.016), and recent thymic emigrant Tregs (P = 0.015).<br><br>CONCLUSIONS: Vagal tone is impaired in patients with nvAMD which disharmonizes with increased Tregs in the systemic circulation. These altered regulators may be the key to increased systemic inflammation, present in patients with nvAMD.},
}
@article {pmid41058830,
year = {2025},
author = {Miki, R and Shiba, T and Oshitari, T and Usui, T},
title = {Evaluation of the Correlation of Reading Ability and Fixation Status in Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91705},
pmid = {41058830},
issn = {2168-8184},
abstract = {Purpose The purpose of this study was to evaluate the correlation of the reading ability obtained by Minnesota low vision reading (MNREAD) and the fixation status by microperimetry and morphological status in Japanese patients with neovascular age-related macular degeneration (nAMD). Material and methods We analyzed 25 consecutive nAMD patients and selected patients if the distance log MAR best corrected visual acuity (BCVA) of the studied eye was from 0.3 to 1.0. For reading ability, the reading visual acuity, maximum reading speed (MRS), and critical print size (CPS) were evaluated. Fixation stability (FS) was defined by the percentage of fixation points located within a circle of diameter 2° centered on all fixation points. For morphological status, central retinal thickness (CRT) and lesion size were evaluated. Multiple regression analyses were used to determine independent contributing factors for MRS and CPS. Single regression analyses were also used to determine the relationship between 2°FS, preferred retinal locus (PRL)-fovea distance, and other parameters. Results Fifteen patients had unilateral nAMD, and 10 patients had bilateral nAMD. The lesion size was identified as a factor independently contributing to the MRS. The BCVA of the fellow eye and 2°FS were identified as factors independently contributing to the CPS. The CRT and PRL-fovea distance were significantly negatively correlated with the 2°FS, and age was significantly negatively correlated with the PRL-fovea distance. Conclusion It is possible that there is a relationship between morphology, fixation status, and reading ability in Japanese patients with nAMD.},
}
@article {pmid41057440,
year = {2025},
author = {Lim, SH and Yamaguchi, TCN and Herrmann, R and Lee, EK and Bae, KH and Park, UC and Park, KH and Yoon, CK},
title = {Influence of subretinal drusenoid deposit on retinal sensitivity in age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {34952},
pmid = {41057440},
issn = {2045-2322},
mesh = {Humans ; Female ; *Retinal Drusen/physiopathology/diagnostic imaging/pathology ; *Macular Degeneration/physiopathology/diagnostic imaging/pathology ; Aged ; Male ; *Retina/physiopathology/diagnostic imaging/pathology ; Tomography, Optical Coherence ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; Visual Field Tests ; Fluorescein Angiography ; },
abstract = {This retrospective study aimed to assess the impact of subretinal drusenoid deposit (SDD), also known as reticular pseudodrusen, on retinal sensitivity (RS) in patients with intermediate age-related macular degeneration (iAMD) using microperimetry. Eyes meeting the modified criteria of iAMD, including SDD, and total drusen area greater than 0.50 mm[2] were included. The presence of SDD, as well as soft drusen (SD), and specific type of SDD (dot or ribbon) were determined through multimodal imaging modalities including fundus photography, fundus autofluorescence, infrared reflectance image and optical coherence tomography. RS was measured using MAIA microperimetry. A total of 302 eyes from 302 patients were analyzed. Patients with SDD were older and predominantly female. Average RS was significantly lower in eyes with SDD than without SDD. (19.75 (5.06) vs. 21.21 (4.53) (average (SD)), P = 0.003). The presence of SD alone did not significantly affect RS. Among eyes with SDD, those with ribbon-type SDD exhibited significantly lower RS (18.02 ± 6.49) than those with dot-type SDD (20.67 ± 4.13; P < 0.001). In multivariable linear regression analysis, older age and the presence of ribbon-type SDD were significantly associated with reduced RS. In conclusion, eyes with iAMD and SDD demonstrate reduced RS, with ribbon-type SDD exerting a greater negative impact on retinal function than dot-type SDD.},
}
@article {pmid41055014,
year = {2025},
author = {Eppenberger, LS and Mohanna, S and Ferdowsi, S and Simon-Zoula, S and Pfäffli, O and Amstutz, C and Bachmann, LM and Thiel, MA and Schmid, MK},
title = {Characterization of retinal pigment epithelium layer in healthy and diseased retinas with high-resolution adaptive optics transscleral flood illumination imaging.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70016},
pmid = {41055014},
issn = {1755-3768},
abstract = {PURPOSE: The retinal pigment epithelium (RPE) is critical in the pathophysiology of retinal diseases, such as age-related macular degeneration. Adaptive optics transscleral flood illumination (AO-TFI) offers rapid, detailed morphometric characterization of the RPE layer. This study evaluated AO-TFI's efficacy and feasibility to detect clinically relevant morphological characteristics in a clinical setting.<br><br>METHODS: A total of 230 participants, categorized by their central retinal health, underwent comprehensive examination including SD-OCT, fundus imaging and AO-TFI using the Cellularis&#xae; prototype 2.0. Image quality control and RPE layer quantification were performed with an AO-TFI-specific automated segmentation algorithm. Density and area of hyper- and hyporeflective regions in the RPE layer plane, and, if detectable, RPE cell density, were quantified. We hypothesized that the RPE cell density would be lower in diseased retinas than in healthy retinas. Imaging results of healthy participants were statistically compared to those of diseased eyes. Additionally, generalized linear and logistic regression mixed-effect models identified associations between ocular characteristics and imaging parameters.<br><br>RESULTS: After quality evaluation, high-quality images from 200 subjects (87%) were selected and segmented. The number of hyperreflective regions and their mean surface area were significantly higher in diseased than in healthy eyes (68&#x2009;&#xb1;&#x2009;40/mm[2] vs. 51&#x2009;&#xb1;&#x2009;39/mm[2]; p&#x2009;<&#x2009;0.001; 302&#x2009;&#xb1;&#x2009;196&#x2009;&#x3bc;m[2] vs. 155&#x2009;&#xb1;&#x2009;55&#x2009;&#x3bc;m[2]; p&#x2009;<&#x2009;0.001). The RPE distinct mosaic pattern was more often visible in healthy retinas (n&#x2009;=&#x2009;103 vs. n&#x2009;=&#x2009;30, p&#x2009;<&#x2009;0.0001). The mean RPE cell density was 6354&#x2009;&#xb1;&#x2009;695/mm[2], with comparable counts for healthy and diseased, 6327&#x2009;&#xb1;&#x2009;687/mm[2] vs. 6532&#x2009;&#xb1;&#x2009;725/mm[2] (p&#x2009;=&#x2009;0.1).<br><br>CONCLUSION: AO-TFI detected differences between healthy and diseased eyes, indicating its potential as a promising clinical modality providing quantitative and qualitative insights into RPE layer dynamics.},
}
@article {pmid41054065,
year = {2025},
author = {Wu, Y and Liu, Y and Jiao, Z and Chen, X and Li, H and Pan, M and Liu, G},
title = {Association between body roundness index and age-related macular degeneration: A cross-sectional analysis of NHANES 2005-2008.},
journal = {Medicine},
volume = {104},
number = {40},
pages = {e44875},
pmid = {41054065},
issn = {1536-5964},
support = {2023J01852//Natural Science Foundation of Fujian Province, China/ ; 2021ZQNZD012//Fujian Major Research Grants for Young and Middle-aged Health Professionals/ ; X2022018-SP//Special Project of Fujian University of Traditional Chinese Medicine/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; Nutrition Surveys ; United States/epidemiology ; Aged ; Adult ; Waist Circumference ; Risk Factors ; ROC Curve ; Body Mass Index ; Logistic Models ; Body Height ; },
abstract = {The specific relationship between body roundness index (BRI) and age-related macular degeneration (AMD) in US adults aged 40 years and older remains insufficiently understood. This study aimed to elucidate the association between BRI and AMD. Data were sourced from the National Health and Nutrition Examination Survey conducted in the United States from 2005 to 2008. The BRI was calculated using anthropometric measurements, specifically height and waist circumference (WC). AMD was diagnosed based on distinct ocular characteristics observed in fundus photographs, evaluated through a recognized grading classification system. Weighted logistic regression analyses were conducted to examine the association between BRI and AMD. Spline smoothing and threshold effects were utilized to identify potential linear or nonlinear correlations. Subgroup analyses were performed to investigate possible factors influencing this relationship. Additionally, receiver operating characteristic (ROC) curve analysis was employed to evaluate predictive capability of BRI for AMD. This study included a total of 5033 participants. The findings indicated a significant positive association between BRI and the risk of AMD in both unadjusted and adjusted logistic regression models (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 1.07-1.31; OR: 1.37, 95% CI: 1.14-1.66). When BRI was divided into quartiles, the highest quartile demonstrated a stronger association with AMD risk compared to the lowest quartile (OR: 1.70, 95% CI: 1.16-2.49) in the unadjusted categorical model. Subgroup analyses and interaction tests confirmed the consistency of the BRI-AMD relationship across various populations. Spline smoothing and threshold effect analyses indicated an approximately positive linear relationship between BRI and AMD incidence in the general population. Furthermore, ROC analysis showed that BRI was slightly more effective in predicting AMD compared to body mass index (BMI) and WC. Since the area under the curve values for BRI, BMI, and WC were 0.549, 0.533, and 0.504, they all showed limited discriminatory performance for AMD prediction. Moreover, the ROC analysis of multi-model comparisons revealed that a combination of WC, BMI, and BRI provided a little better predictive capability for AMD prevalence than any single predictive model. There is a positive association between BRI and AMD among US adults aged 40 years and older. BRI serves as a modest predictor of obesity for forecasting AMD risk. Strategies for managing obesity related to BRI are essential for the prevention and treatment of AMD to some extent.},
}
@article {pmid41053370,
year = {2025},
author = {Bowley, N and Thomas, P and Sivaprasad, S and Purbrick, RMJ and Beardmore, E and Gilbert, R and Clarke, A and Chase, TJG},
title = {Sustainability in medical retina: the environmental impact of using aflibercept 8 mg instead of aflibercept 2 mg in treatment-naïve patients with nAMD.},
journal = {Eye (London, England)},
volume = {39},
number = {17},
pages = {3160-3166},
pmid = {41053370},
issn = {1476-5454},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; United Kingdom ; *Carbon Footprint ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {BACKGROUND/OBJECTIVES: Sustainability is a major concern with the use of intravitreal therapy for neovascular age-related macular degeneration (nAMD), as case numbers rise with the ageing population. The aim of this study is to quantify the difference in the carbon emissions from factory gate to patient between aflibercept 2 mg pre-filled syringe (PFS) and aflibercept 8 mg PFS when used over the first 2 years in treatment-naïve patients with nAMD in the UK.<br><br>METHODS: The carbon footprint per injection was calculated by adding carbon emissions-obtained from internal corporate and published data-for packaging creation, transport, patient travel and waste disposal for each product. Results were extrapolated to a UK population using an estimate of the number of injections from real-world evidence and/or clinical trial data and the published incidence of nAMD.<br><br>RESULTS: Between factory and patient, the carbon emissions for aflibercept 2&#x2009;mg PFS are approximately 2.3&#x2009;kg CO2 per injection, compared with 2.1&#x2009;kg CO2 for aflibercept 8&#x2009;mg PFS. Using aflibercept 8&#x2009;mg PFS instead of aflibercept 2&#x2009;mg PFS for treatment-na&#xef;ve patients with nAMD in the UK would result in ~68,000-272,000 fewer hospital visits over the first 2 years and decrease emissions by ~277,000-736,000&#x2009;kg CO2.<br><br>CONCLUSIONS: Using aflibercept 8&#x2009;mg PFS instead of aflibercept 2&#x2009;mg PFS in treatment-na&#xef;ve patients with nAMD has benefits for the environment and National Health Service (NHS) capacity and would therefore help meet NHS sustainability goals.},
}
@article {pmid41053127,
year = {2025},
author = {Li, Y and Yarahmadov, T and Jahnke, L and Brodie, T and Morandi, SC and Stroka, D and Hafezi-Moghadam, A and Zinkernagel, MS and Enzmann, V and Zandi, S},
title = {Rho-kinase inhibition reduces subretinal fibrosis.},
journal = {Cell death discovery},
volume = {11},
number = {1},
pages = {428},
pmid = {41053127},
issn = {2058-7716},
support = {DP3 DK108238/DK/NIDDK NIH HHS/United States ; INO-2016-222-A-N//JDRF/United States ; DK108238-01//U.S. Department of Health &amp; Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health)/ ; 202008520042//China Scholarship Council (CSC)/ ; },
abstract = {Subretinal fibrosis, a consequence of choroidal neovascularization (CNV) in age-related macular degeneration (AMD), leads to irreversible vision loss due to excessive accumulation of extracellular matrix (ECM) proteins and fibrotic scarring. Anti-VEGF therapy can reverse neovascularization, but its effect on fibrosis is relatively limited. To reduce the visual impact of the fibrosis that remains after CNV. Our study investigated the use of ROCK inhibitors, fasudil and belumosudil, to treat subretinal fibrosis after CNV. The results confirmed that levels of key fibrotic markers (TGF-β1, fibronectin, vimentin, α-SMA and pMYPT1) were lower after treatment. IMC provided detailed spatial mapping of protein expression, revealing significant changes in structure and cellular composition before and after the treatment. We found that fasudil and belumosudil are effective in attenuating subretinal fibrosis by modulating the ROCK-signaling pathway, reducing ECM remodeling and attenuating the expression of markers associated with fibrosis. We hope to provide a basis for maximizing clinical benefit, focusing on optimizing dose and timing of treatment, exploring combination therapies for future anti-subretinal fibrosis research.},
}
@article {pmid41053106,
year = {2025},
author = {Geiger, F and Heigl, T and Merolla, L and Yong, M and Wögenstein, GM and Govers, LP and Tsioti, I and Fottner, A and Samardzija, M and Grimm, C},
title = {HIF1 activity in photoreceptors drives type 3 neovascularization and retinal atrophy in a new mouse model of age-related macular degeneration.},
journal = {Cell death &amp; disease},
volume = {16},
number = {1},
pages = {687},
pmid = {41053106},
issn = {2041-4889},
support = {310030_200798//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; },
mesh = {Animals ; *Macular Degeneration/pathology/metabolism/genetics ; Disease Models, Animal ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Mice ; Retinal Pigment Epithelium/pathology/metabolism ; Atrophy ; *Retinal Neovascularization/pathology/metabolism/genetics ; Humans ; Mice, Inbred C57BL ; Retina/pathology/metabolism ; *Retinal Rod Photoreceptor Cells/metabolism/pathology ; *Neovascularization, Pathologic/pathology/metabolism ; },
abstract = {Morphological changes in the ageing eye impede oxygen delivery from the choroid to the outer retina causing tissue hypoxia, which activates a molecular response that adapts the transcriptomic fingerprint of the retina and retinal pigment epithelium (RPE). This response, orchestrated by hypoxia-inducible transcription factors (HIFs), leads to the production of pro-angiogenic factors and plays a critical role in the development and pathogenesis of age-related macular degeneration (AMD). To evaluate the specific contribution of HIF1 to this response we expressed a constitutively active form of HIF1A in rod photoreceptors of the adult mouse retina. This elicited a transcriptional response characterized by the upregulation of genes involved in cell death, inflammation and angiogenesis, all of which play an important role in AMD. The HIF1-mediated response in rods caused severe retinal degeneration, disruption of the RPE and retinal neovascularization. Pathological vessels originated from the deep vascular plexus and penetrated the RPE resembling type 3 macular neovascularization observed in over 20% of patients with neovascular AMD. Our study provides further evidence for the involvement of tissue hypoxia in the pathogenesis of AMD and highlights the potential of HIF1A as a therapeutic target.},
}
@article {pmid41053100,
year = {2025},
author = {Youale, J and Bigot, K and Jaworski, T and Lebon, C and Françon, A and Delaunay, K and Bénard, R and De Bastard, T and Daruich, A and Kaddour, N and Bordet, T and Behar-Cohen, F and Picard, E},
title = {Transferrin is a drug candidate for the treatment of dry age-related macular degeneration (AMD).},
journal = {Cell death &amp; disease},
volume = {16},
number = {1},
pages = {692},
pmid = {41053100},
issn = {2041-4889},
support = {ANR-20-CE18-0023//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-20-CE18-0023//Agence Nationale de la Recherche (French National Research Agency)/ ; },
mesh = {Humans ; *Transferrin/therapeutic use/pharmacology/metabolism ; *Macular Degeneration/drug therapy/pathology/metabolism ; Iron/metabolism ; Oxidative Stress/drug effects ; Aged ; Female ; Male ; Ferroptosis/drug effects ; Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Geographic Atrophy/drug therapy/pathology/metabolism ; Aged, 80 and over ; Homeostasis/drug effects ; },
abstract = {Dysregulation of iron homeostasis plays a crucial role in retinal diseases, contributing to oxidative stress, inflammation, and ferroptosis, key processes that drive the degeneration of the retinal pigment epithelium (RPE) and photoreceptors in age-related macular degeneration (AMD). Previous studies, though limited in patient numbers, have reported elevated iron levels in the aqueous humor, RPE, and Bruch's membrane of AMD patients. In this study, we aimed to confirm iron imbalance in a larger cohort of AMD patients and assess its correlation with disease stage. Elevated iron levels and a reduction in transferrin (TF) iron-binding capacity were observed in patients with early geographic atrophy (GA). RPE cells derived from human stem cells exhibited AMD-like features when exposed to iron overload or oxidized lipids. Treatment with TF appeared to restore aspects of iron homeostasis and reduce oxidative stress, mitochondrial damage, inflammation, complement activation, and ferroptosis in this model. These findings suggest that TF supplementation may represent a potential therapeutic strategy to help prevent or slow AMD progression.},
}
@article {pmid41051727,
year = {2025},
author = {Tatemoto, Y and Hayashi, T and Mizobuchi, K and Den, S and Nakano, T},
title = {Best vitelliform macular dystrophy caused by a BEST1 p.(Ser246Asn) variant coexisting with diabetic retinopathy.},
journal = {Documenta ophthalmologica. Advances in ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41051727},
issn = {1573-2622},
support = {JP25K20191//Japan Society for the Promotion of Science London/ ; JP24K12771//Japan Society for the Promotion of Science London/ ; JPMH23FC1043//MHLW/ ; },
abstract = {PURPOSE: To report a 42 year-old male patient with Best vitelliform macular dystrophy (BVMD) complicated by diabetic retinopathy, who harbored a missense variant in the BEST1 gene.<br><br>METHODS: Comprehensive ophthalmological examinations, including full-field electroretinography (ERG) and electrooculography (EOG), were performed. Whole exome sequencing (WES) was conducted to identify potential disease-causing variant(s), and Sanger sequencing was used for confirmation.<br><br>RESULTS: Fundus photography and fluorescein angiography revealed macular degeneration and non-proliferative diabetic retinopathy with macular leakage. Although the light peak/dark trough (Arden) ratio on EOG was relatively preserved, a reduced light rise and attenuated dark trough amplitudes were observed. ERG demonstrated normal rod and cone system function. Based on optical coherence tomography findings, the BVMD stage was classified as a stage between the Vitelliruptive and Atrophic stages in the right eye, and as the Pseudohypopyon stage in the left eye. WES identified a previously unreported BEST1 variant, c.737G&#x2009;>&#x2009;A: p.(Ser246Asn) heterozygously, confirmed by Sanger sequencing.<br><br>CONCLUSIONS: This case emphasizes the importance of EOG assessment and genetic analysis in establishing an accurate diagnosis of BVMD, particularly in patients with coexisting conditions such as diabetic retinopathy.},
}
@article {pmid41050312,
year = {2025},
author = {Ueberroth, JA and Oellers, PR and Eliott, D},
title = {Electroretinographic Response Following Inadvertent Intravitreal Injection of Lidocaine 2.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251366411},
pmid = {41050312},
issn = {2474-1272},
abstract = {Purpose: To describe the visual and electroretinographic (ERG) outcomes after inadvertent intravitreal injection of lidocaine. Methods: A 75-year-old man with neovascular age-related macular degeneration inadvertently received approximately 0.07 mL of lidocaine 2% intravitreally in his right eye. Serial 30 Hz flicker ERG was performed at 3, 6, and 24 hours postinjection. Results: Visual acuity decreased to count fingers immediately after the injection and returned to baseline of 20/30 within 24 hours. ERG showed increased amplitudes at 3 hours in the affected eye (47.7 microvolts) relative to the unaffected eye (35.7 microvolts) that normalized at hours 6 (23.5 microvolts OD, 29.1 microvolts OS) and 24 (13.4 microvolts OD, 11.8 microvolts OS). Mean implicit time (26.97 ms OD, 27.0 ms OS) was symmetric. Conclusions: In our case, visual acuity reduction and ERG changes specific to 0.07 mL intravitreal lidocaine 2% seem to be transient and may not require any specific therapy other than immediate intraocular pressure control.},
}
@article {pmid41049435,
year = {2025},
author = {Yang, Y and Zhang, R and Zhang, M and Yang, Z and Ma, Z and Zhang, Y and Wu, M and Guo, D and Bi, H},
title = {Association between Disorders of Lipid Metabolism and Oculopathy: An Overview.},
journal = {International journal of medical sciences},
volume = {22},
number = {15},
pages = {3878-3894},
pmid = {41049435},
issn = {1449-1907},
mesh = {Humans ; *Eye Diseases/pathology/metabolism/etiology ; *Lipid Metabolism Disorders/complications/metabolism/pathology ; *Lipid Metabolism ; Oxidative Stress ; Eye/pathology/metabolism ; },
abstract = {Lipid metabolism disorders, which lead to lipid deposition or changes in blood lipid composition, play a significant role in inducing or exacerbating the pathogenesis of diseases such as hypercholesterolemia and diabetes. Moreover, these disorders are closely associated with the development and progression of ocular diseases, including corneal degeneration, cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy. Studies have shown that lipid metabolism disorders critically impact the structure and function of ocular tissues through mechanisms such as lipid deposition, disrupted cholesterol synthesis, abnormal lipid concentrations, or impaired lipid transport. These disorders can damage cellular structures, induce oxidative stress, disrupt signal transduction, and lead to apoptosis of ocular tissue cells, mitochondrial dysfunction, and osmotic imbalance, ultimately impairing normal physiological functions and contributing to the onset of various eye diseases. This article reviews the association between lipid metabolism disorders and the development of various ocular diseases and explores the mechanisms underlying the interaction between lipid metabolism abnormalities and eye diseases, as well as the preventive role of lipid metabolism regulation in ocular diseases.},
}
@article {pmid41049111,
year = {2026},
author = {Li, T and Yang, S and Liu, Q and Song, Y and Tong, J and Wei, W and Chen, W and Dai, H and Wang, W and Wu, M and Zhou, G and Xiao, X and Zhang, J and Zhu, R and Li, H and Wang, Y and Chen, X and Lu, S and Du, H and Han-Zhang, H and Hao, J and Li, C and Wen, Y and Zhang, J and Sun, J and Jia, H and Sun, X},
title = {Efficacy and Safety of Efdamrofusp Alfa with Personalized Dosing Intervals in Neovascular Age-Related Macular Degeneration: A Phase II Trial.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100913},
pmid = {41049111},
issn = {2666-9145},
abstract = {PURPOSE: This study aims to evaluate the efficacy and safety of high-dose efdamrofusp alfa (IBI302, targeting VEGF and complement C3b/4b) with personalized dosing intervals in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: A multicenter, randomized, double-masked, active-controlled, noninferiority phase II trial.<br><br>PARTICIPANTS: A total of 132 anti-VEGF na&#xef;ve or previously treated participants with nAMD were enrolled.<br><br>METHODS: Eligible participants were randomized (1:1:1) to receive IBI302 6.4 mg, IBI302 8.0 mg, or aflibercept 2.0 mg. Efdamrofusp alfa groups were dosed every 8 weeks (Q8W) or every 12 weeks (Q12W), based on disease activity assessment at week 20, after 4 monthly injections. The aflibercept 2.0-mg group was dosed Q8W, after 3 monthly injections.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 40. The prespecified noninferiority margin was 4 letters.<br><br>RESULTS: The least squares mean (standard error) changes in BCVA from baseline to week 40 were +10.5 (1.5) letters with IBI302 6.4 mg, +9.2 (1.5) letters with IBI302 8.0 mg, and +9.7 (1.5) letters with aflibercept 2.0 mg. The estimated differences were +0.8 (80% confidence interval: -1.9 to 3.6, noninferiority test: P = 0.0115) for IBI302 6.4 mg versus aflibercept 2.0 mg and -0.5 (-3.3 to 2.2, noninferiority test: P = 0.0123) for IBI302 8.0 mg versus aflibercept 2.0 mg. Over 80% of participants in IBI302 groups were dosed Q12W after week 20 and maintained their regimens until the end of study. Treatment-emergent adverse events (TEAEs) in the study eye were reported in 36.4% of participants receiving IBI302 6.4 mg, 37.8% receiving IBI302 8.0 mg, and 23.3% receiving aflibercept 2.0 mg. The most common ocular TEAE was conjunctival hemorrhage (9.1% for 6.4 mg and 11.1% for 8.0 mg) in both IBI302 groups, whereas cataract (7.0%) was the most frequent ocular TEAE in the aflibercept 2.0-mg group.<br><br>CONCLUSIONS: Efdamrofusp alfa 6.4 and 8.0 mg dosed up to Q12W demonstrated noninferior visual gain to aflibercept 2.0 mg Q8W. Moreover, IBI302 groups were well tolerated. These findings suggested that high-dose IBI302 with extended dosing intervals could provide sustained visual benefits for patients with nAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid41048962,
year = {2025},
author = {Zhong, J and Yao, C and Jin, Y},
title = {Global trends and hotspots of inflammation in diabetic retinopathy: a literature review and bibliometric analysis.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1615045},
pmid = {41048962},
issn = {2296-858X},
abstract = {BACKGROUND: Diabetic retinopathy (DR) is a global public health problem, with inflammation playing a pivotal role in its progression. In this study, we aimed to assess the current research landscape of inflammation in DR and identified emerging frontiers using bibliometric analysis.<br><br>METHODS: Relevant publications were retrieved from the Web of Science Core Collection database, and VOSviewer and CiteSpace were used for bibliometric analysis and visualization.<br><br>RESULTS: Overall, 3,419 publications on inflammation in DR over the past 44&#x202f;years were identified, exhibiting an upward trend. China had the highest number of publications, while the United States had the majority of citations. Shanghai Jiao Tong University was the most active institution, and Investigative Ophthalmology Visual Science was the most productive journal. Timothy S. Kern contributed the most publications, with the highest total/average citations. Research mainly focused on the risk factors, mechanisms, and potential therapies in this field. Key areas of future exploration include the roles of the NLRP3 inflammasome and gut microbiota, the correlation between DR and age-related macular degeneration, and advancements in identification techniques and optical coherence tomography.<br><br>CONCLUSION: We provide a systematic overview of the academic literature on inflammation in DR over the past few decades. The United States and China have been pivotal in conducting research in this field. Optical coherence tomography screening and the precise identification of inflammation in DR are likely to emerge as the next area of focus. Further understanding the roles of NLRP3 and the gut microbiota in inflammation in DR is also a potential research direction. Additionally, identifying the mechanisms of inflammation underlying DR and age-related macular degeneration is a cutting-edge and urgent research priority.},
}
@article {pmid41047829,
year = {2025},
author = {Du, Y and Sahraie, Y and Das, M and Katsimpris, A},
title = {Efficacy of Initial Intravitreal Faricimab Injection after Switching from Aflibercept to Faricimab in Treatment-Resistant Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {},
number = {},
pages = {1-12},
doi = {10.1159/000548751},
pmid = {41047829},
issn = {1423-0259},
abstract = {PURPOSE: Previous studies have demonstrated the efficacy of Faricimab where the intervention in treatment-resistant neovascular age-related macular degeneration (nAMD) had been switched from Aflibercept to Faricimab. This exploratory study aimed to assess the clinical anatomical and functional outcomes of a single intravitreal Faricimab (IVF) injection in those with treatment-resistant nAMD who switched from Aflibercept, in a single tertiary ophthalmology centre.<br><br>METHODS: This retrospective, observational real-world study assessed 20 patients (21 eyes) with treatment-resistant nAMD who were switched from intravitreal Aflibercept (IVA) to Faricimab due to persistent subretinal fluid (SRF) despite frequent Aflibercept injections. Patients were switched to a regimen of Faricimab consisting of three loading doses administered at 4-weekly injections. Anatomical and functional measures were assessed at two time points: immediately before the initial Faricimab injection and approximately 4 weeks later, before the second Faricimab injection. The outcome measures were: visual acuity, central macular thickness (CMT), macular volume, and the presence of SRF were evaluated pre- and post-switch.<br><br>RESULTS: Twenty-one eyes from 20 patients were analyzed. Statistically significant reductions in CMT (from 570.2 to 482.7 &#x3bc;m; p < 0.01) and macular volume (from 8.57 to 7.87 mm&#xb3;; p = 0.02) were observed post-switch, while the change in visual acuity did not reach statistical significance (p = 0.051). The number of eyes with SRF decreased from 21 pre-switch to 9 post-switch.<br><br>CONCLUSION: The findings from this exploratory study suggests that switching from Aflibercept to Faricimab demonstrated significant physiological improvements among patients with treatment-resistant nAMD. Faricimab may serve as an effective and safe option in this patient population. The exploratory study also identifies changes in CMT and macular volume as outcome measure candidates for future large-scale investigations.},
}
@article {pmid41047158,
year = {2025},
author = {Olivieri, C and Neri, G and Ricardi, F and Gelormini, F and Fai, A and Parisi, G and Marolo, P and Viggiano, P and Boscia, F and Reibaldi, M and Borrelli, E},
title = {Comparative diagnostic performance of six imaging modalities for detecting macular atrophy in neovascular age-related macular degeneration.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328225},
pmid = {41047158},
issn = {1468-2079},
abstract = {PURPOSE: To evaluate the diagnostic accuracy of six imaging modalities-colour fundus photography (CFP), multicolour imaging (MC), blue autofluorescence (BAF), green autofluorescence (GAF), near-infrared reflectance (NIR) and structural optical coherence tomography (OCT)-for detecting macular atrophy (MA) in patients with previously treated neovascular age-related macular degeneration (AMD).<br><br>METHODS: This retrospective cohort study included 113 eyes from patients treated with anti-vascular endothelial growth factor for at least 1 year. All eyes underwent six imaging modalities during the same visit. MA was identified by a senior retinal specialist using multimodal criteria and served as the diagnostic reference (ie, gold standard). Sensitivity and specificity of each imaging modality were calculated relative to this reference. Two masked graders independently assessed images using modality-specific definitions of MA. Discrepancies were resolved by consensus. Sensitivity, specificity, positive predictive value, negative predictive value and inter-reader agreement were calculated for each modality.<br><br>RESULTS: MA was present in 46.9% of eyes based on multimodal imaging. Structural OCT detected MA in 43.4% of cases, followed by GAF (36.3%), BAF and NIR (35.4% each), MC (33.6%) and CFP (30.1%). Structural OCT demonstrated the highest diagnostic accuracy, with 92.4% sensitivity and 96.7% specificity. Other modalities showed moderate sensitivity (64.1-77.4%) and specificity (75.0-88.3%). Inter-reader agreement was moderate for BAF (&#x3ba;=0.46) and lower for the remaining modalities, lowest for CFP (&#x3ba;=0.18).<br><br>CONCLUSIONS: Structural OCT offers the highest accuracy and reliability for detecting MA in neovascular AMD, supporting its use in both clinical practice and research. Other modalities may supplement OCT when needed, but CFP alone is limited.},
}
@article {pmid41043824,
year = {2025},
author = {Yang, WYL and Chay, IWJ and Lim, HB and Tan, MCL and See, B and Low, JW},
title = {Pachychoroid Neovasculopathy, Intravitreal Injection, and Implications for Aeromedical Decision Making.},
journal = {Aerospace medicine and human performance},
volume = {96},
number = {10},
pages = {940-946},
doi = {10.3357/AMHP.6665.2025},
pmid = {41043824},
issn = {2375-6322},
mesh = {Humans ; Intravitreal Injections ; Male ; *Aerospace Medicine ; *Choroidal Neovascularization/drug therapy ; Military Personnel ; Visual Acuity ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Central Serous Chorioretinopathy/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Singapore ; Pilots ; },
abstract = {BACKGROUND: Optimal visual function is essential in aviation to ensure flight safety and mission effectiveness. Pachychoroid neovasculopathy is a relatively recently recognized clinical entity of choroidal neovascularization, belonging to the pachychoroid spectrum, for which intravitreal therapy (IVT) is the standard of care. The main aeromedical considerations are degradation of visual function from disease progression, which could preclude aircrew from flying duties, and the compatibility of IVT with flying.<br><br>CASE REPORT: A trained Republic of Singapore Air Force aircrew operator on board the Fokker-50 first presented with a reduction in visual acuity at his annual aircrew medical examination, for which he was restricted from flying duties for further evaluation. He was diagnosed with central serous chorioretinopathy and treated conservatively, but subsequently developed pachychoroid neovasculopathy. He was started on monthly IVT for 3 mo before being placed on a treat-and-extend regimen. After 10 mo of treatment totalling five doses of aflibercept IVT, he achieved resolution of subretinal fluid and recovery of visual acuity, stereopsis, and color vision. He was returned to flying duties upon full recovery, with a close follow-up regimen with his attending ophthalmologist and flight surgeon.<br><br>DISCUSSION: Pachychoroid neovasculopathy can cause degradation of visual function and visual incapacitation, posing differential threats to flight safety and mission success based on an aircrew's vocational roles. The aviation environment could also influence disease progression. Furthermore, aeromedical considerations for IVT are increasingly relevant as IVT becomes the standard of care for prevalent conditions, including neovascular age-related macular degeneration and diabetic macular edema. Yang WYL, Chay IWJ, Lim HB, Tan MCL, See B, Low JW. Pachychoroid neovasculopathy, intravitreal injection, and implications for aeromedical decision making. Aerosp Med Hum Perform. 2025; 96(10):940-946.},
}
@article {pmid41043515,
year = {2025},
author = {Merle, DA and Beretta, F and Sacconi, R and Querques, G},
title = {Fibrogliosis in neovascular age-related macular degeneration: A new mechanistic perspective.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.09.019},
pmid = {41043515},
issn = {1879-3304},
abstract = {Age-related macular degeneration (AMD) remains among the leading causes of blindness in industrialized nations, with fibrosis secondary to macular neovascularization (MNV) significantly contributing to visual decline despite treatment with anti-vascular endothelial growth factor therapy. Although traditionally viewed as detrimental, fibrosis may reflect a delicate balance between beneficial vessel stabilization and harmful scarring. We critically evaluate the pathophysiology of fibrosis in AMD and introduces the novel hypothetical concept of "fibrogliosis", which emphasizes the central role of Müller glia and retinal microglia activation following disruption of the outer blood-retinal barrier. According to this concept, fibrogliosis manifests differently among MNV subtypes, influenced largely by their impact on outer blood-retinal barrier integrity. Recognizing this variability underscores the importance of further investigation into the hypothetical concept of fibrogliosis, which in theory could guide future therapeutic strategies to balance vascular stabilization with the modulation of neovascularization and fibrosis.},
}
@article {pmid41042032,
year = {2025},
author = {Park, J and Kazemi, M and Tamhane, M and Shen, J},
title = {Computational Fluid Dynamics Modeling of Intravitreal Ranibizumab Bolus Versus Subretinal ABBV-RGX-314 Transgene Product in Human Eyes.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {10},
pages = {6},
pmid = {41042032},
issn = {2164-2591},
mesh = {*Ranibizumab/pharmacokinetics/administration &amp; dosage ; Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage ; Animals ; Aqueous Humor/metabolism ; Hydrodynamics ; Retina/metabolism ; Computer Simulation ; Macaca fascicularis ; *Recombinant Fusion Proteins/pharmacokinetics ; *Wet Macular Degeneration/drug therapy/metabolism ; },
abstract = {PURPOSE: ABBV-RGX-314 is being developed for neovascular age-related macular degeneration (nAMD). Computational fluid dynamics (CFDs) modeling in the eye enables simulation of drug distribution incorporating geometry and substructures of the eye across species. Given the similarity between ranibizumab and ABBV-RGX-314 transgene product (TP), ranibizumab intraocular pharmacokinetic (PK) data from literature were used to simulate intraocular drug distribution of ABBV-RGX-314 TP. This investigation aims to use CFD modeling to estimate retinal TP level based on aqueous humor (AH) TP level following subretinal (SR) injection of ABBV-RGX-314 in patients with nAMD.<br><br>METHODS: Ocular distribution of ranibizumab following a single intravitreal (IVT) injection was modeled in both monkey and human eyes independently. Following model validation, ABBV-RGX-314 TP distribution in human eyes was simulated following retinal transduction of ABBV-RGX-314.<br><br>RESULTS: Iterative simulations were performed to achieve similar AH ABBV-RGX-314 TP levels in patients with nAMD from phase I/IIa Study RGX-314-001. The CFD simulation estimated corresponding retinal TP concentrations of 1.86 to 5.50 &#xb5;g/g at steady-state, which was assumed to be reached by 28 days and falls within the range of the estimated retinal ranibizumab trough retinal ranibizumab concentration (Ctrough; 0.718-5.37 &#xb5;g/g) following monthly and every other month (EOM) dosing of 0.5 mg ranibizumab in patients with nAMD.<br><br>CONCLUSIONS: The current study results predict that the 2 pivotal trial ABBV-RGX-314 doses (6.4E10 and 1.3E11 genome copies/eye) are expected to achieve and maintain sufficient retinal ABBV-RGX-314 TP levels for the treatment of nAMD.<br><br>TRANSLATIONAL RELEVANCE: CFD modeling effectively bridges limited human ocular PK data with rich preclinical data, supporting model-informed drug development (MIDD) for clinical dose selection.},
}
@article {pmid41041280,
year = {2025},
author = {Chakraborty, S and Sheth, JU and Ganguly, S and Reddy, R},
title = {Efficacy and Safety of Intravitreal Brolucizumab in Chronic Central Serous Chorioretinopathy: A Retrospective Cohort Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3557-3565},
pmid = {41041280},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the anatomical and functional outcomes and treatment burden of intravitreal brolucizumab in chronic central serous chorioretinopathy (cCSCR) over 12 months in a real-world setting.<br><br>PATIENTS AND METHODS: In this retrospective, single-center cohort, 29 eyes with cCSCR received pro re nata intravitreal brolucizumab. Baseline OCT angiography excluded macular neovascularization. Patients were seen monthly for three months, then as needed through month 12. At each visit, best-corrected visual acuity (BCVA), central retinal thickness (CRT), and presence of SRF, intraretinal fluid (IRF), and pigment epithelium detachment (PED; including PED height) were recorded. Total injections per eye were tallied.<br><br>RESULTS: Twenty-nine eyes (mean age 55.2&#xb1;11.0 years; 72% male) with cCSCR received 1.72 &#xb1; 0.62 intravitreal brolucizumab injections over 12 months. Vision improved from BCVA 0.59 &#xb1; 0.23 logMAR at baseline to 0.46 &#xb1; 0.22 at one month (P=0.002), 0.40 &#xb1; 0.20 at three months (P<0.001), and 0.39 &#xb1; 0.20 at month 12 (P<0.001). Mean CRT reduced from 340 &#xb1; 140&#xa0;&#xb5;m to 260 &#xb1; 110&#xa0;&#xb5;m at one month and stabilized at 230 &#xb1; 98&#xa0;&#xb5;m by month 12 (P<0.001). Mean PED height decreased from 48 &#xb1; 55&#xa0;&#xb5;m at baseline to 13 &#xb1; 17&#xa0;&#xb5;m at month 12 (P<0.001). Fluid resolution was rapid and sustained; SRF cleared in 63% at one month (P<0.001) and 88.9% at 12 months (P<0.001), IRF in 85.7% by month 3 (P=0.016) and 71.4% by month 12 (P=0.063), and PEDs in 43.8% at one month (P=0.021) rising to 68.8% at month 12 (P=0.001). No ocular or systemic adverse events occurred.<br><br>CONCLUSION: Intravitreal brolucizumab provided significant and sustained visual and anatomical improvements in cCSCR with a low injection burden over 12 months. Given the off&#x2011;label use and absence of a control group, findings should be interpreted cautiously and confirmed in prospective controlled studies.},
}
@article {pmid41041025,
year = {2024},
author = {Katoch, K and Sharma, RK and Mahajan, VK and Tuli, R},
title = {Ophthalmic Comorbidities in Patients with Chronic Plaque Psoriasis: A Hospital-Based Cross-Sectional Study of 100 Patients.},
journal = {Journal of current ophthalmology},
volume = {36},
number = {4},
pages = {419-427},
pmid = {41041025},
issn = {2452-2325},
abstract = {PURPOSE: To study the characteristics of ophthalmic comorbidities in patients with chronic plaque psoriasis.<br><br>METHODS: We assessed the clinical and epidemiological attributes and characteristics of ophthalmic comorbidities of patients who had chronic plaque psoriasis for 15-25 years (mean &#xb1; standard deviation [SD], 3.9 &#xb1; 4.8 years). Out of 100 patients, 57 were males and 43 were females. In this cohort, the age range was from 19 to 77 years (mean &#xb1; SD, 41.8 &#xb1; 13.9 years). The severity of psoriasis was defined by the psoriasis area severity index (PASI) score as mild (PASI &#x2264;6), moderate (PASI >6-12), or severe (PASI >12).<br><br>RESULTS: Psoriasis was mild in 77, moderate in 13, and severe in 10 patients, respectively. Three patients had asymmetric oligoarthritis. In a cohort of 100 patients, there were 23 patients with moderate-to-severe psoriasis and 77 patients with mild psoriasis. In the moderate-to-severe psoriasis group, 18 out of the 23 patients also had ophthalmic abnormalities. In the mild psoriasis group, 53 of 77 patients also had ophthalmic abnormalities. Itching (n = 12; psoriasis was mild in 7, moderate-to-severe in 5 patients), decreased vision (n = 12; psoriasis was mild in 10, moderate-to-severe in 2 patients), redness (n = 9; psoriasis was mild in 5, moderate-to-severe in 5 patients;), watering/discharge (n = 8; psoriasis was mild in 6, moderate-to-severe in 2 patients), and pain or burning (n = 6; psoriasis was mild in 4, moderate-to-severe in 2 patients) were commonly complained by 31 patients. The major ophthalmic comorbidities in order of frequency observed were keratoconjunctivitis sicca/dry eye (n = 41), blepharitis (n = 29), meibomian gland dysfunction (MGD) (n = 18), conjunctivitis (n = 10), corneal abnormalities (n = 13), cataract (n = 14), retention cyst (n = 2), and anterior uveitis in 2 patients (without psoriatic arthritis). Common corneal abnormalities were punctuate keratitis (n = 7), corneal opacities (n = 4), band-shaped keratopathy (n = 1), and superficial vascularization (n = 1). Posterior segment manifestations of arteriosclerotic changes (n = 4), media haze (n = 2), and macular degeneration (n = 1) were likely to be age-related.<br><br>CONCLUSIONS: The ophthalmic comorbidities, such as blepharitis, MGD, conjunctivitis, keratoconjunctivitis sicca, corneal abnormalities, and presenile cataract, can occur in patients with psoriasis. These are largely asymptomatic and subtle findings that are often missed. They require an early consult to ophthalmology for appropriate management. The major limitations in this study are that it is a single-center, cross-sectional study design that has a low number of patients, lacks a healthy patient control group, and there is a lack of long-term follow-up.},
}
@article {pmid41040794,
year = {2025},
author = {Sato, M and Kageyama, K and Ito, S and Ino, Y and Bunchuailua, W and Rungpragayphan, S and Yamazaki, T and Sugishita, K and Krichanchai, S and Nakao, S and Sriamornsak, P and Takeuchi, H and Nakamura, M},
title = {Evaluation of Intraocular Anti-vascular Endothelial Growth Factor (VEGF) Drug-Associated Adverse Events Using Spontaneous Reporting Databases.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e91376},
pmid = {41040794},
issn = {2168-8184},
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) agents are the first-line therapies for macular edema, diabetic macular edema, and exudative age-related macular degeneration secondary to retinal vein occlusion. Although adverse events, including cerebral infarction, are rare, their potential severity warrants further investigation. This study aimed to evaluate the risk and time to onset of adverse events, including cerebral infarction, associated with anti-VEGF agents using the Japanese Adverse Drug Event Report (JADER) database.<br><br>METHODS: Adverse events were coded using the Medical Dictionary for Regulatory Activities, and reporting odds ratios were calculated. The number of reports and median time to onset (interquartile range) were determined.&#xa0;Survival analyses were performed employing the log-rank test and the generalized Wilcoxon test.<br><br>RESULTS: From April 2004 to January 2025, 965,286 reports were included in the JADER database. The number of adverse event reports for aflibercept (IVA), ranibizumab (IVR), brolucizumab (IVB), and faricimab (IVF) was 1,217, 1,223, 1,064, and 199, respectively. Furthermore, the reported numbers of cerebral infarction cases associated with IVA, IVR, IVB, and IVF were 200, 154, 16, and 20, respectively. The median (interquartile range) time to onset of cerebral infarction associated with IVA and IVR was 79.0 (range: 28.0-274.0) days and 48.5 (range: 14.0-142.5) days, respectively, with a significant difference in the time trend (log-rank test: p = 0.0100 and generalized Wilcoxon test: p = 0.0067).<br><br>CONCLUSION: The findings suggest that cerebral infarction may develop earlier with IVR use than with IVA use and highlight the need for careful monitoring and individualized treatment strategies in clinical practice.},
}
@article {pmid41039072,
year = {2025},
author = {Sharma, A and Nicholson, L and Vazquez-Alfageme, C and Sivagnanavel, V and Fausto, R and Soare, MC and Salamanca, MB and Fabozzi, L and Tsika, C and Corbalan, OC and Verdejo, AG and Wakabayashi, T and Woo, SJ and Kolomeyer, AM and Mansour, H and Momenaei, B and Regillo, CD and , },
title = {FYB-201 Biosimilar ranibizumab (Ongavia/Ranivisio/Cimerli) Efficacy and Safety in Clinical Settings - FORCE study.},
journal = {Eye (London, England)},
volume = {39},
number = {17},
pages = {3129-3134},
pmid = {41039072},
issn = {1476-5454},
mesh = {Humans ; *Ranibizumab/therapeutic use/adverse effects/administration &amp; dosage ; Female ; Male ; Retrospective Studies ; *Biosimilar Pharmaceuticals/therapeutic use/adverse effects/administration &amp; dosage ; Intravitreal Injections ; Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; Aged ; Middle Aged ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Macular Edema/drug therapy ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To understand the early experience of ranibizumab biosimilar (FYB 201) that has been approved in the United Kingdom (Ongavia, Teva Pharmaceuticals, Tel Aviv Israel), United States (Cimerli, Sandoz Inc, Princeton, NJ, USA) and Europe (Ranivisio, Bioeq AG, Zug, Switzerland).<br><br>METHODS: 1230 patients received 3595 ranibizumab biosimilar (FYB 201) injections for variable indications in this multicentric retrospective study. All patients were treated with at least one intravitreal injection of ranibizumab biosimilar (FYB 201) 0.5&#x2009;mg. Primary outcome was best-corrected visual acuity (BCVA). Secondary outcome was central foveal thickness&#xa0;(CFT). Other outcome measures included adverse events.<br><br>RESULTS: A total of 3595 ranibizumab biosimilar (FYB 201) injections were given for neovascular age-related macular degeneration (n-AMD) (n&#x2009;=&#x2009;802), other causes of choroidal neovascularization (CNV) (n&#x2009;=&#x2009;36), diabetic macular oedema (DMO) (n&#x2009;=&#x2009;169), retinal vein occlusion (RVO) (n&#x2009;=&#x2009;155), myopic macular neovascularisation (m-MNV) (n&#x2009;=&#x2009;61), cystoid macular oedema (CMO) (n&#x2009;=&#x2009;6) and proliferative diabetic retinopathy (n&#x2009;=&#x2009;1). Mean age was 77.2&#x2009;&#xb1;&#x2009;12.7 years and 80.9% were females. The mean follow-up period was 15.7&#x2009;&#xb1;&#x2009;9.9 weeks after the first injection of ranibizumab biosimilar (FYB 201). Overall, the mean BCVA remained stable from 0.57&#x2009;&#xb1;&#x2009;0.21 at baseline to 0.56&#x2009;&#xb1;&#x2009;1.8 at the last follow-up (p&#x2009;=&#x2009;0.84, 95% CI -0.0915 to 0.1115). The mean CFT was significantly reduced from 260.5&#x2009;&#xb1;&#x2009;141.8 &#x3bc;m at baseline to 211.4&#x2009;&#xb1;&#x2009;113.2 &#x3bc;m at the last follow-up (p&#x2009;=&#x2009;0.0001, 95% CI 38.935 to 59.265). Three eyes (0.24%) had ocular adverse events and 6 patients (0.48%) experienced systemic adverse events during the study period.<br><br>CONCLUSION: Ranibizumab biosimilar (FYB 201) injections were effective and safe in this real-world experience, with stable visual acuity and reduced CFT with no major complications.},
}
@article {pmid41034984,
year = {2025},
author = {Yap, CL and Tan, TF and Tan, ACS and Schmetterer, L and Wong, D},
title = {Lesion detection in age-related macular degeneration with a multi-modal imaging and machine learning approach.},
journal = {Biomedical engineering online},
volume = {24},
number = {1},
pages = {111},
pmid = {41034984},
issn = {1475-925X},
support = {OFLCG/004c/2018-00; MOH-000249-00; MOH-000647-00; MOH-001001-00; MOH-001015-00; MOH-000500-00; MOH-000707-00; MOH-001072-06; MOH-001286-00//National Medical Research Council/ ; NRF2019-THE002-0006 and NRF-CRP24-2020-0001//National Research Foundation Singapore/ ; A20H4b0141//Agency for Science, Technology and Research/ ; STANCE//Singapore Eye Research Institute &amp; Nanyang Technological University/ ; },
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/pathology ; *Machine Learning ; *Multimodal Imaging/methods ; Tomography, Optical Coherence ; *Image Processing, Computer-Assisted/methods ; ROC Curve ; Aged ; },
abstract = {BACKGROUND: Age-related macular degeneration is a leading cause of central vision loss, and assessing visual function with microperimetry can be time-consuming and tiring for patients. Targeting regions corresponding to worsening acute-stage retinal lesions may reduce test durations and patient fatigue.<br><br>RESULTS: We developed a machine-learning approach using multi-modal imaging data to differentiate lesional regions from healthy retinal areas. Our dataset included 344,003 regions extracted from color fundus photographs, infrared fundus images, optical coherence tomography, and optical coherence tomography angiography images. A gradient-boosted tree-ensemble model was trained on this data and achieved an area under the receiver operating characteristic curve of 0.95 in detecting end-stage lesions in chronic age-related macular degeneration.<br><br>CONCLUSIONS: The proposed method effectively detects lesions associated with age-related macular degeneration using multi-modal imaging and machine learning. This approach offers a potential solution for creating targeted microperimetry test patterns, which can reduce testing time and patient fatigue, thereby enhancing the clinical assessment of visual function in affected patients.},
}
@article {pmid41034378,
year = {2025},
author = {Li, J and Wang, B and Liu, P and Qiu, X and Bian, Q and Shen, C and Li, Y and Shao, M and Li, M},
title = {Intermittent fasting attenuates glial hyperactivation and photoreceptor degeneration in a NaIO3-induced mouse model of age-related macular degeneration.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1408},
pmid = {41034378},
issn = {2399-3642},
support = {82371401//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100769//National Natural Science Foundation of China (National Science Foundation of China)/ ; 24KJA310011//Jiangsu Provincial Department of Education (Department of Education Jiangsu Province)/ ; },
mesh = {Animals ; *Macular Degeneration/chemically induced/pathology/metabolism/prevention &amp; control ; Iodates/toxicity ; Mice ; Disease Models, Animal ; Male ; *Fasting/physiology ; *Neuroglia/metabolism/pathology ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/pathology/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; *Photoreceptor Cells, Vertebrate/pathology/metabolism ; Intermittent Fasting ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss, with limited treatments available. Recent studies suggest intermittent fasting (IF) may offer neuroprotective benefits for aging and age-related disorders, but its efficacy in AMD has not yet been established. Here, using a sodium iodate (NaIO3)-induced AMD model in male mice, we find that pretreatment with an IF diet regimen mitigates NaIO3-induced cellular damage and loss of both retinal pigment epithelium (RPE) and photoreceptors. Visual function tests indicate that IF preserves vision in NaIO3-treated mice. Transcriptome analyses show IF counteracts NaIO3-induced transcriptional dysregulation, affecting genes related to reactive oxygen species (ROS), inflammation, and photoreceptor structure. Further experimental results confirm that IF effectively reduces ROS levels and inhibits the activation of microglia and Muller cells in the retina. Collectively, these findings indicate that IF reduces ROS production and inflammation in NaIO3-induced retinal damage, providing a potential therapeutic strategy for oxidative stress-induced retinal degenerative diseases, including AMD.},
}
@article {pmid41034043,
year = {2025},
author = {Lee, JR and Kim, MR and Jeong, KW},
title = {Activator protein-1 mediates blue light-induced phototoxicity in retinal pigment epithelial cells.},
journal = {The Journal of toxicological sciences},
volume = {50},
number = {10},
pages = {569-576},
doi = {10.2131/jts.50.569},
pmid = {41034043},
issn = {1880-3989},
mesh = {Humans ; *Retinal Pigment Epithelium/radiation effects/cytology/pathology/metabolism ; *Transcription Factor AP-1/metabolism/physiology/genetics ; Apoptosis/radiation effects/genetics ; *Light/adverse effects ; Cell Line ; Signal Transduction/radiation effects ; Retinoids ; Phosphorylation ; Tumor Suppressor Protein p53/metabolism/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism ; bcl-2-Associated X Protein/metabolism ; Macular Degeneration/etiology ; Proto-Oncogene Proteins c-jun/metabolism ; Blue Light ; },
abstract = {Age-related macular degeneration is a leading cause of vision loss and is characterized by the accumulation of drusen in the retinal pigment epithelium. N-retinylidene-N-retinylethanolamine (A2E), a major component of drusen, induces phototoxicity upon exposure to blue light. Given that blue light activates the MAPK pathway and triggers apoptosis, the present study aimed to determine the role of signaling via the activator protein-1 (AP-1) transcription factor in A2E-laden ARPE-19 cells. RNA-sequencing identified significant upregulation of the UV response and p53 pathways. In silico analysis predicted that JUN was a key upstream transcriptional regulator, and experimental validation confirmed increased JUN phosphorylation and AP-1 target gene expression upon blue light exposure. Furthermore, blue light treatment decreased BCL2 and increased BAX protein levels, thereby promoting apoptosis via caspase activation and PARP cleavage, as also confirmed by flow cytometry. These findings suggest that blue light induces apoptosis via JUN, which activates AP-1 in A2E-laden ARPE-19 cells. The present study provides new insights into the molecular mechanisms underlying blue light-induced retinal damage and its potential contribution to the progression of age-related macular degeneration.},
}
@article {pmid41032557,
year = {2025},
author = {Fazekas, B and Aresta, G and Seebock, P and Mai, J and Schmidt-Erfurth, U and Bogunovic, H},
title = {SD-RetinaNet: Topologically Constrained Semi-Supervised Retinal Lesion and Layer Segmentation in OCT.},
journal = {IEEE transactions on medical imaging},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TMI.2025.3615240},
pmid = {41032557},
issn = {1558-254X},
abstract = {Optical coherence tomography (OCT) is widely used for diagnosing and monitoring retinal diseases, such as age-related macular degeneration (AMD). The segmentation of biomarkers such as layers and lesions is essential for patient diagnosis and follow-up. Recently, semi-supervised learning has shown promise in improving retinal segmentation performance. However, existing methods often produce anatomically implausible segmentations, fail to effectively model layer-lesion interactions, and lack guarantees on topological correctness. To address these limitations, we propose a novel semi-supervised model that introduces a fully differentiable biomarker topology engine to enforce anatomically correct segmentation of lesions and layers. This enables joint learning with bidirectional influence between layers and lesions, leveraging unlabeled and diverse partially labeled datasets. Our model learns a disentangled representation, separating spatial and style factors. This approach enables more realistic layer segmentations and improves lesion segmentation, while strictly enforcing lesion location in their anatomically plausible positions relative to the segmented layers. We evaluate the proposed model on public and internal datasets of OCT scans and show that it outperforms the current state-of-the-art in both lesion and layer segmentation, while demonstrating the ability to generalize layer segmentation to pathological cases using partially annotated training data. Our results demonstrate the potential of using anatomical constraints in semi-supervised learning for accurate, robust, and trustworthy retinal biomarker segmentation.},
}
@article {pmid41031745,
year = {2025},
author = {Pu, J and Zhuang, X and Li, M and Hao, X and He, G and Su, Y and Xia, L and Wen, F},
title = {Early Fluctuations of Exudative Lesions as Predictors of Two-Year Clinical Outcomes in Neovascular Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {10},
pages = {1},
pmid = {41031745},
issn = {2164-2591},
mesh = {Humans ; Aged ; Male ; Female ; Prospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Middle Aged ; Ranibizumab/therapeutic use/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Intravitreal Injections ; Subretinal Fluid ; Prognosis ; Fluorescein Angiography ; Treatment Outcome ; Exudates and Transudates ; },
abstract = {PURPOSE: To investigate how early fluctuations of exudative lesions correlate with 2-year outcomes in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study included 92 treatment-na&#xef;ve nAMD eyes treated with anti-vascular endothelial growth factor (anti-VEGF) therapy using a 3+PRN regimen over 2 years. Volumes of seven exudative lesion types were measured: subretinal fluid (SRF); intraretinal fluid (IRF); vascular and avascular subretinal hyperreflective material (vSHRM and avSHRM, respectively); and serous, fibrovascular, and hemorrhagic pigment epithelial detachment (sPED, fvPED, and hPED, respectively). Four fluctuation parameters were calculated during the 3-month loading phase. Relationships between these early fluctuations and clinical outcomes, including best-corrected visual acuity (BCVA) and injection frequency, were analyzed.<br><br>RESULTS: A total of 92 eyes (92 patients) were included, with a mean age of 65.65 &#xb1; 7.20 years. After adjusting for baseline characteristics, fluctuations in both vSHRM and avSHRM were identified as independent predictors of 2-year BCVA prognosis, with greater fluctuations associated with poorer visual outcomes (vSHRM Std&#x3b2; range, 0.671-0.797; avSHRM Std&#x3b2; range, 0.722-0.856; all P &#x2264; 0.001). However, only IRF fluctuation metrics were found to be independently associated with injection frequency over 2 years (Std&#x3b2; range, 0.327-0.532; all P < 0.05), with greater fluctuations correlating with more frequent injections.<br><br>CONCLUSIONS: SHRM fluctuations during the loading phase predict 2-year visual outcomes, and IRF variations correlate with injection frequency in nAMD.<br><br>TRANSLATIONAL RELEVANCE: Early fluctuation patterns of exudative lesions can serve as predictive biomarkers to guide personalized anti-VEGF treatment strategies and optimize long-term visual outcomes in nAMD patients.},
}
@article {pmid41031003,
year = {2025},
author = {Zeng, Y and Zhang, T and Cornish, E and Lee, SR and Yam, M and Eminhizer, M and Zeng, J and Zhang, J and Zeng, S and Wei, X and Yang, J and Zhu, M and Chang, A and Zhang, M and Du, J and Zhu, L and Gillies, MC},
title = {Dysregulated Proline Metabolism Contributes to Subretinal Fibrosis in Neovascular AMD: Therapeutic Potential of Prolyl-4-Hydroxylase Inhibition.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.04.13.648057},
pmid = {41031003},
issn = {2692-8205},
abstract = {Subretinal fibrosis, a major cause of irreversible vision loss in neovascular age-related macular degeneration (nAMD), is driven by excessive deposition of extracellular matrix such as collagens. While proline metabolism is known to play a critical role in collagen biosynthesis and fibrosis, its involvement in subretinal fibrosis remains unclear. Here, we characterized the progression of fibrovascular lesions in JR5558 mice, observing significant molecular alterations as early as 4 weeks of age and phenotypic changes by 8 weeks. Transcriptomic and metabolomic analyses revealed elevated levels of 4-hydroxyproline, an essential component of collagen, alongside significant alterations of other fibrosis-related pathways. P4HA1, a catalytic subunit of prolyl-4-hydroxylase essential for 4-hydroxyproline biosynthesis, was prominently expressed in fibrotic lesions in retinas of JR5558 and two-stage laser-induced murine models, as well as human eyes with nAMD. Targeting P4HA1 with the small-molecule inhibitor diethyl pythiDC significantly attenuated fibrovascular lesion growth in the JR5558 murine models and reduced collagen turnover in human retinal pigment epithelium cells. Combining diethyl pythiDC with aflibercept had a stronger antifibrotic effect than monotherapies in JR5558 mice. These findings suggest a key contribution of proline metabolism, particularly proline hydroxylation, in subretinal fibrosis. Inhibiting P4HA1 with diethyl pythiDC inhibited fibrosis in the models we studied, offering a novel therapeutic strategy. Further research is warranted to explore the potential benefits of combining existing anti-angiogenic therapies with drugs that inhibit proline metabolism for the management of nAMD-associated fibrosis.},
}
@article {pmid41029559,
year = {2025},
author = {Park, SM and Shin, D and Kim, CG and Kim, JH},
title = {Characteristics of geographic atrophy secondary to age-related macular degeneration in Korean patients.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {516},
pmid = {41029559},
issn = {1471-2415},
abstract = {PURPOSE: To evaluate the characteristics of geographic atrophy (GA) in the Korean population and investigate the factors associated with visual acuity.<br><br>METHODS: Patients with complete retinal pigment epithelium and outer retinal atrophy were considered to have GA. The characteristics of GA, including lesion type (monofocal or multifocal), total lesion size, foveal involvement, best-corrected visual acuity, and subfoveal choroidal thickness (SCT), were evaluated. The incidence of pachychoroid GA and factors associated with better visual acuity (&#x2265;&#x2009;20/40) were also determined.<br><br>RESULTS: This study included 104 eyes of 68 patients with a mean age of 77.6&#x2009;&#xb1;&#x2009;7.0 years. Bilateral GA was detected in 52.9% of patients. Monofocal and multifocal lesions were observed in 49% and 51% of the eyes, respectively. The mean lesion size was 9.9&#x2009;&#xb1;&#x2009;8.9&#xa0;mm&#xb2;. Foveal involvement was observed in 41.3% of eyes. The mean SCT was 154.6&#x2009;&#xb1;&#x2009;90.1&#xa0;&#x3bc;m, and pachychoroid GA was detected in 7.7% of eyes. Greater central retinal thickness and the absence of foveal involvement were associated with better visual acuity.<br><br>CONCLUSIONS: The prevalence of bilateral GA and larger lesions were higher while the prevalence of pachychoroid GA was lower among our patients than among those included in previous studies involving East Asian populations. This study highlights the diverse characteristics of GA in Koreans and suggests that patients with GA characteristics comparable to those observed in Western populations may be frequently encountered depending on the center.},
}
@article {pmid41029554,
year = {2025},
author = {AlJohani, S and Khathami, AA and Shehri, AA},
title = {Factors influencing ophthalmology trainees' decision to pursue vitreoretinal surgery fellowship in Saudi Arabia: a cross-sectional study.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {519},
pmid = {41029554},
issn = {1471-2415},
mesh = {Humans ; Cross-Sectional Studies ; Saudi Arabia ; Male ; Female ; *Career Choice ; *Vitreoretinal Surgery/education ; *Ophthalmology/education ; *Fellowships and Scholarships ; *Internship and Residency ; Adult ; Surveys and Questionnaires ; *Education, Medical, Graduate ; },
abstract = {BACKGROUND: The demand for vitreoretinal surgery (VRS) specialists is increasing globally due to the rising prevalence of retinal diseases such as diabetic retinopathy and age-related macular degeneration. In Saudi Arabia, the burden of retinal diseases is particularly high, with diabetic retinopathy affecting about one-third of diabetic patients. Despite this, factors influencing ophthalmology trainees' decisions to pursue VRS fellowship remain underexplored. This study aimed to identify the key factors shaping career decisions among ophthalmology trainees in Saudi Arabia.<br><br>METHODS: A cross-sectional study was conducted between July and December 2024, targeting senior ophthalmology residents and vitreoretinal surgery fellows across Saudi Arabia. A purposive sampling method was used, and data were collected via an online survey adapted from a validated tool and assessed for content validity. The survey explored exposure to VRS, research opportunities, mentorship, and career motivations using a 5-point Likert scale. Descriptive statistics and nonparametric Mann-Whitney U tests were applied.<br><br>RESULTS: A total of 61 trainees participated, of whom 35 (57.4%) reported pursuing a VRS fellowship. Male trainees were significantly more likely to pursue VRS than females (88.6% vs. 46.2%, p&#x2009;<&#x2009;0.001). Most VRS pursuers reported deciding during residency years R2-R3, and 40% had performed over 100 cataract procedures. Major motivators included strong interest in complex surgeries (74.3%), advanced technology (51.4%), and the perceived prestige of VRS (54.3%). Exposure to VRS, research opportunities, and program match success were significantly associated with career choice, while mentorship and work-life balance played a lesser role.<br><br>CONCLUSION: The decision to pursue vitreoretinal surgery among ophthalmology trainees in Saudi Arabia is primarily influenced by early exposure, surgical complexity, and perceived prestige. Gender disparities remain evident, with male trainees more likely to enter VRS, partly due to limited female mentorship. Enhancing mentorship opportunities and fostering early exposure may help address these disparities and sustain interest in the subspecialty.},
}
@article {pmid41028859,
year = {2025},
author = {Nagel, ID and Tran, MD and Zhang, H and Cheng, L and Heinke, A and Mehta, NN and Bartsch, DU and Kalaw, FGP and Morsy, M and Mueller, AJ and Freeman, WR},
title = {Faricimab at 6 and 12 mg reduces pigment epithelium detachment in treatment-resistant macular neovascularization: an OCT and AI analysis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33950},
pmid = {41028859},
issn = {2045-2322},
support = {P30EY022589//UCSD Vision Research Center Core Grant/ ; P30EY022589//UCSD Vision Research Center Core Grant/ ; P30EY022589//UCSD Vision Research Center Core Grant/ ; R01EY016323//NIH grant/ ; R01EY016323//NIH grant/ ; R01EY016323//NIH grant/ ; 5R01EY033847//NIH Grant/ ; 5R01EY033847//NIH Grant/ ; 5R01EY033847//NIH Grant/ ; OT2OD032644//National Institutes of Health Bridge2AI Project/ ; OT2OD032644//National Institutes of Health Bridge2AI Project/ ; },
mesh = {Humans ; Male ; Female ; Tomography, Optical Coherence ; Aged ; *Retinal Detachment/drug therapy/diagnostic imaging ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Cross-Sectional Studies ; *Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Aged, 80 and over ; *Retinal Pigment Epithelium/drug effects/pathology ; Intravitreal Injections ; Middle Aged ; Treatment Outcome ; Antibodies, Bispecific ; },
abstract = {Macular neovascularization (MNV) in age-related macular degeneration (AMD) remains a therapeutic challenge, especially in eyes resistant to conventional anti-VEGF therapy. This study evaluates the anatomical and functional response to Faricimab in patients with persistent fluid despite intensified Aflibercept treatment and explores potential benefits of dose escalation. This cross-sectional study included 25 eyes from 23 patients with active MNV resistant to standard anti-VEGF therapy. All had persistent fluid on OCT despite monthly injections and received off-label double-volume Aflibercept 4 mg (0.1 ml) for at least three doses. Eyes with persistent fluid were switched to Faricimab 6 mg. In non-responders, Faricimab was further escalated to 12 mg (0.1 ml). Retinal fluid volumes and pigment epithelium detachment (PED) were analyzed using AI-based OCT segmentation. MNV activity was assessed using AI-based OCTA analysis. Faricimab 6 mg significantly reduced PED volume (p < 0.05), especially after the first two injections. However, changes in intraretinal and subretinal fluid were not significant. In the Faricimab 12 mg subgroup, no additional anatomical benefit was observed. OCTA showed a trend toward reduced vascular activity after switching to Faricimab 6 mg, but no further change with dose escalation. In MNV eyes resistant to high-dose Aflibercept, Faricimab 6 mg provides meaningful anatomical improvement, particularly in PED volume. However, escalating Faricimab to 12 mg offers no additional benefit, suggesting therapeutic saturation at the standard dose.},
}
@article {pmid41025875,
year = {2025},
author = {Reiter, GS and Birner, K and Schrittwieser, J and Hinterhuber, L and Steiner, I and Gumpinger, M and Schürer-Waldheim, S and Bogunovic, H and Schmidt-Erfurth, U},
title = {Deep-Learning-Based Analysis of Disease-Specific Structural Biomarkers on Retinal Sensitivity in Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {12},
pages = {68},
pmid = {41025875},
issn = {1552-5783},
mesh = {Humans ; Aged ; Cross-Sectional Studies ; Female ; Male ; Tomography, Optical Coherence/methods ; Prospective Studies ; *Deep Learning ; Biomarkers ; *Wet Macular Degeneration/physiopathology/diagnosis ; Aged, 80 and over ; Visual Field Tests/methods ; Visual Acuity/physiology ; *Visual Fields/physiology ; *Retina/physiopathology/diagnostic imaging ; Fluorescein Angiography ; },
abstract = {PURPOSE: To evaluate the impact of disease-specific biomarkers on pointwise sensitivity (PWS) in patients with active neovascular age-related macular degeneration (nAMD) using two microperimetry (MP) instruments.<br><br>METHODS: Participants in this prospective cross-sectional study underwent imaging with a SPECTRALIS HRA+OCT and MP with the photopic MP-3 (NIDEK) and mesopic MAIA (CenterVue). Pigment epithelium detachment (PED), intraretinal and subretinal fluid (IRF, SRF), ellipsoid zone loss (EZL), and subretinal hyperreflective material (SHRM) were quantified using deep learning (DL). DL enabled co-registration between the MP and optical coherence tomography (OCT). Univariate and multivariable mixed-effects models using variable selection including interaction terms were used to assess the effects of the biomarkers on PWS.<br><br>RESULTS: Twenty eyes of 20 subjects (mean age, 76.0 years) were included. Sensitivity in the MAIA was lower (-2.87 dB; 95% confidence interval [CI], -3.15 to -2.59) than in the MP-3. Significant interactions between EZL and SRF, EZL and IRF, and between EZL and eccentricity were observed. EZL significantly reduced PWS (-1.30 dB; 95% CI, -2.08 to -0.51) at 0&#xb0; eccentricity with SRF of 0.15 nL and absent IRF. IRF presence further decreased PWS by -2.57 dB (95% CI, -3.66 to -1.47). SRF negatively impacted PWS (-2.08 dB/nL; 95% CI, -2.53 to -1.64), but showed no association when EZL was present (+0.05 dB/nL; 95% CI, -0.81 to 0.92). SHRM presence and PED volume reduced PWS by -5.13 dB (95% CI, -5.83 to -4.43) and -0.71 dB/nL (95% CI, -0.92 to -0.50), respectively. Eccentricity only impaired function in the presence of EZL (-0.49 dB/&#xb0;; 95% CI, -0.61 to -0.37).<br><br>CONCLUSIONS: DL-quantified biomarkers mostly had a negative impact on PWS in nAMD, particularly IRF and SHRM presence. The above-mentioned biomarkers should be considered when managing patients with nAMD and using MP in trials and clinical settings.},
}
@article {pmid41024579,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX},
title = {External limiting membrane defects in age-related macular degeneration. The Beijing Eye Study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70015},
pmid = {41024579},
issn = {1755-3768},
support = {82271086//National Natural Science Foundation of China/ ; },
abstract = {PURPOSE: To assess the prevalence and associations of external limiting membrane (ELM) defects on optical coherence tomographic (OCT) images in a general population, affected by age-related macular degeneration (AMD) or free of any retinal disease.<br><br>METHODS: Using OCT images, we assessed the ELM defect presence in participants of the population-based Beijing Eye Study.<br><br>RESULTS: The study population consisted of 712 (44.2%) eyes with early AMD, 295 (18.3%) eyes with intermediate AMD, 12 (0.7%) eyes with geographic atrophy and 592 (36.7%) eyes without signs of AMD. ELM defect prevalence increased from 6/592 (1.0%; 95% CI: 0.0, 2.0) in the normal group to 57/712 (8.0%; 95% CI: 6.0, 10.0), 117/295 (39.7%; 95% CI: 34.2, 45.2) and 11/12 (91.7%; 95% CI: 73.7, 100) in the group with early AMD stage, intermediate AMD and late AMD stage, respectively. Higher ELM defect prevalence was spatially associated with higher prevalence of ellipsoid zone (EZ) defects (OR: 929; 95% CI: 291-2964; p&#x2009;<&#x2009;0.001). In multivariable analysis, higher ELM defect prevalence correlated with higher AMD stage (OR: 2.22; 95% CI: 1.33, 3.71; p&#x2009;=&#x2009;0.002), higher prevalence of intraretinal hyperreflective foci (iHRFs) superior to the EZ/ELM (OR: 29.7; 95% CI: 8.69-102; p&#x2009;<&#x2009;0.001), lower prevalence of iHRFs beneath the EZ/ELM (OR: 0.11; 95% CI: 0.04, 0.35; p&#x2009;<&#x2009;0.001) and higher prevalence of localized interdigitation zone thinnings (IZTs) (OR: 5.66; 95% CI: 3.14, 10.2; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: The spatial correlation between ELM defects and EZ defects, the associations of both defect types with a higher occurrence of iHRFs superior to the ELM, the association between an absence of ELM defects and a higher prevalence of iHRFs located inferior to the ELM, and the association between a higher ELM defect prevalence and higher IZT prevalence may suggest the ELM/EZ may act as a barrier for RPE cells migrating into the retina.},
}
@article {pmid41024135,
year = {2025},
author = {Rath, S and Ibrahim, AA and Singh, A and Das, A and Sediqi, SM and Khan, NA and Panchal, K and Mian, SM},
title = {Efdamrofusp alfa: an insight into the novel drug and its use in age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {100},
pmid = {41024135},
issn = {2056-9920},
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in older adults, with its prevalence rising globally. This review aims to explore the potential of Efdamrofusp alfa (EA), a novel bispecific decoy receptor fusion protein targeting both VEGF and complement pathways, in treating neovascular AMD (nAMD).<br><br>METHODS: A comprehensive literature search was conducted across PubMed, Cochrane and Embase till March 2025 to find articles evaluating the efficacy of EA in the treatment of neovascular AMD. Observations from early pre-clinical studies and clinical trials were analyzed to determine the efficacy and safety of EA.<br><br>RESULTS: A total of five preclinical and clinical studies were included, encompassing 66 animal subjects and 880 human participants. Efdamrofusp alfa (IBI302) neutralizes both C3b/C4b and VEGF, demonstrating anti-angiogenic effects in preclinical models. Clinical trials examined intravitreal doses ranging from 0.05&#xa0;mg to 4.00&#xa0;mg. EA showed efficacy in reducing central retinal thickness and improving visual acuity, with a safety profile comparable to existing anti-VEGF treatments. Treatment-emergent adverse events (TEAEs) included conjunctival hemorrhage, ocular hypertension, and keratitis, which were similar to those observed with other intravitreal anti-VEGF drugs. The drug demonstrated noninferiority to aflibercept in improving best-corrected visual acuity (BCVA) and significantly reduced central subfield thickness.<br><br>CONCLUSIONS: Efdamrofusp alfa shows promise as a novel treatment for nAMD, potentially offering improved efficacy over current anti-VEGF therapies. Nonetheless, further large-scale randomized clinical trials are essential to confirm its efficacy and safety in broader populations. The dual-inhibition strategy provides a new avenue for personalized AMD treatment, particularly for patients unresponsive to monotherapies.},
}
@article {pmid41023746,
year = {2025},
author = {Qu, Y and Liu, Y and Fang, J and Chen, C and Cheng, L and Xu, X and Jin, J and Chen, X and Niu, T and Wang, H and Xing, X and Shi, X and Shen, Y and Liu, K},
title = {Dysregulated serum lipid profiles in neovascular age-related macular degeneration revealed by UPLC‒MS/MS lipidomics.},
journal = {Lipids in health and disease},
volume = {24},
number = {1},
pages = {302},
pmid = {41023746},
issn = {1476-511X},
support = {82171071, 81870667//the National Natural Science Foundation of China/ ; project number YG2025ZD26//the Fundamental Research Funds for the Central Universities/ ; 21XD1402700//Program of Shanghai Academic/Technology Research Leader under the Science and Technology Innovation Action Plan/ ; No. SHDC2022CRD001//the Clinical Research Plan of Shenkang Hospital Development Center of Shanghai/ ; 10000015Z155080000004//National Clinical Key Specialty Construction Project/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Lipidomics/methods ; Tandem Mass Spectrometry ; Middle Aged ; Cross-Sectional Studies ; *Lipids/blood ; *Wet Macular Degeneration/blood ; Chromatography, High Pressure Liquid ; Sphingolipids/blood ; Lipid Metabolism ; Prospective Studies ; Carnitine/blood/analogs &amp; derivatives ; Glycerophospholipids/blood ; *Choroidal Neovascularization/blood ; *Macular Degeneration/blood ; China ; Retina/pathology ; Liquid Chromatography-Mass Spectrometry ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is a major aetiology of vision loss characterized by lipid metabolism dysregulation. This study investigated the alterations in lipid profiles associated with wet AMD (wAMD) and its subtype, polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: A cross-sectional lipidomic analysis was derived from a prospective longitudinal study in China (2017-2019). Serum samples from 195 wAMD patients, 130 PCV patients and 119 controls were analysed using ultra-performance liquid chromatography&#x2012;tandem mass spectrometry (UPLC&#x2012;MS/MS), focusing on acylcarnitines, glycerophospholipids and sphingolipids. Training and test sets were randomly generated after sample size matching. Orthogonal partial least squares-discriminant (OPLS-DA), univariate and multivariate analyses were performed. The selection criteria for differential lipids were a variable importance in projection (VIP)&#x2009;>&#x2009;1.0, a fold change (FC)&#x2009;>&#x2009;1.2 or <&#x2009;0.83, and a false discovery rate (FDR)&#x2009;<&#x2009;0.05. Key lipids were refined using the Boruta algorithm and evaluated through Firth regression and receiver operating characteristic (ROC) analysis. Spearman's rank correlation analysis was used to assess the relationships between the differential lipids and ocular indicators, including central retinal thickness (CRT), central retinal volume (CRV) and best-corrected visual acuity (BCVA).<br><br>RESULTS: No significant Lipid profile differences were detected between wAMD and PCV. Compared with the controls, wAMD patients had 53 differential lipids (52 upregulated, 1 downregulated), whereas PCV patients had 34 (31 upregulated, 3 downregulated). Upregulated PC ae C42:0 was consistently associated with ocular indicators in both groups. A 9-lipid panel for wAMD and a 6-lipid panel for PCV showed moderate diagnostic performance in the ROC models. Significant correlations with macular structure and BCVA were observed in PCV patients for 12 phosphatidylcholines, 3 sphingomyelins and 2 acylcarnitines and in wAMD patients for one phosphatidylcholine and one acylcarnitine. Downregulated lipids were negatively correlated with CRT or CRV, whereas upregulated lipids showed the opposite trend. Age-related lipid associations were found in wAMD but not in PCV patients.<br><br>CONCLUSIONS: PCV and wAMD had shared and distinct lipidomic dysregulations, with stronger systemic-retinal associations in PCV, suggesting that subtype-specific metabolic reprogramming may affect nAMD pathology, offering new perspectives regarding early diagnosis and intervention strategies to mitigate disease burden.<br><br>TRIAL REGISTRATION: NCT03128463 (www.<br><br>CLINICALTRIAL: gov) was registered on 9 March 2017.},
}
@article {pmid41023401,
year = {2025},
author = {Demirel, S and Ellialtıoğlu, PA and Yanık, &#xd6; and Cheung, CMG and Chhablani, J and Koh, A and Batıoğlu, F},
title = {Non-indocyanine green angiography non-invasive differentiating features in the differential diagnosis of pachychoroid neovasculopathy and neovascular age-related macular degeneration: a sensitivity-specificity study.},
journal = {Eye (London, England)},
volume = {39},
number = {17},
pages = {3090-3098},
pmid = {41023401},
issn = {1476-5454},
mesh = {Humans ; Female ; Male ; Aged ; Diagnosis, Differential ; Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Choroidal Neovascularization/diagnosis ; Middle Aged ; ROC Curve ; *Choroid/blood supply/pathology ; Coloring Agents/administration &amp; dosage ; *Wet Macular Degeneration/diagnosis ; Indocyanine Green ; Sensitivity and Specificity ; Aged, 80 and over ; Retrospective Studies ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; },
abstract = {OBJECTIVES: To define the differentiating features of pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD) without dye angiography.<br><br>METHODS: This study included treatment-naive 50 PNV patients and 50 nAMD patients with unilateral Type 1 macular neovascularisation (MNV). The studied optical coherence tomography (OCT) features were subretinal hyperreflective material, intraretinal cysts, choroidal thickness (CT), pigment epithelial detachment (PED), retinal pigment epithelium (RPE) changes, and types of drusen. The choroidal vascularity index (CVI) was calculated. Intervortex venous anastomosis, MNV subtypes, and the main trunk appearance on OCT angiography (OCTA) were evaluated. Features with an area under the receiver operating characteristic curve (AUC) above 0.75 were defined as major, while those between 0.60 and 0.75 were defined as minor differentiating features.<br><br>RESULTS: Five features met the criteria for major differentiating features: age &#x2264;60 years, SFCT&#x2009;&#x2265;&#x2009;254&#x2009;&#xb5;m in the diseased eye, CVI&#x2009;&#x2265;&#x2009;72% in the diseased eye, SFCT&#x2009;&#x2265;&#x2009;323&#x2009;&#xb5;m in the fellow eye, and the absence of soft drusen. Six features met the criteria for minor differentiating features: CVI&#x2009;&#x2265;&#x2009;74% in the fellow eye, absence of serous PED, absence of reticular drusen, presence of intervortex anastomoses, presence of immature MNV, and absence of the main trunk on OCTA. The sensitivity, specificity, positive predictive value, negative predictive value, and AUC for at least three major and at least three minor differentiating features are 0.88, 0.96, 0.96, 0.89, and 0.92, respectively.<br><br>CONCLUSION: At least three major and three minor criteria must be present to confidently diagnose PNV.},
}
@article {pmid41022968,
year = {2025},
author = {Neo, EZO and Liang, KWO and Toh, ZH and Tan, ABY and Choy, DMY and Zhou, W and Mi, HF and Lim, LWY and Soh, YQ and Chin, JYH and Thng, ZX and Chia, KJW and Laude, A and Tan, CSH and Lim, TH and Gan, NY and Rajagopalan, R and Ngo, WK},
title = {Real world outcomes of faricimab in treatment resistant neovascular age-related macular degeneration among Asian patients.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33672},
pmid = {41022968},
issn = {2045-2322},
mesh = {Humans ; Male ; Aged ; Female ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/adverse effects ; Tomography, Optical Coherence ; Aged, 80 and over ; Visual Acuity/drug effects ; Treatment Outcome ; Intravitreal Injections ; Ranibizumab/therapeutic use/administration &amp; dosage ; Middle Aged ; *Macular Degeneration/drug therapy ; Singapore ; Asian People ; Recombinant Fusion Proteins/therapeutic use ; Bevacizumab/therapeutic use/administration &amp; dosage ; Antibodies, Bispecific ; Receptors, Vascular Endothelial Growth Factor ; },
abstract = {To describe the real-world efficacy and safety outcome measurements of faricimab use in treatment-resistant neovascular age-related macular degeneration (nAMD) in a cohort of Asian patients. A tertiary hospital in central Singapore serving a resident population of approximately 1.5 million. Retrospective chart review of patients with nAMD previously treated using intravitreal bevacizumab, ranibizumab or aflibercept and were switched to faricimab between August 2022 to August 2023. Patients were switched to faricimab due to either the ineffectiveness of prior anti-VEGF agents to achieve retinal dryness or inadequate treatment intervals. Only patients who had at least one follow-up visit after switching to faricimab were included in the analysis. Primary outcome measures included best-corrected visual acuity (BCVA) in ETDRS letter score and Optical Coherence Tomography (OCT) measurements including central subfield thickness (CST), presence or absence of intraretinal fluid (IRF), subretinal fluid (SRF), intraretinal cysts and subretinal hyperreflective material (SRHM). Secondary outcome measures included adverse events and treatment history such as the mean number of injections and treatment intervals. One hundred and nineteen eyes (117 patients) with a mean age of 75.6 (58-93 years) were switched to faricimab and included in the analysis. Of these, 55 (47.0%) were males. The mean number of intravitreal anti-VEGF injections received was 28.2 ± 19.5 prior to switching to faricimab. The majority of these were switched from ranibizumab (26.1%) and aflibercept (73.1%). At baseline, BCVA was 62.7 ± 19.9 letter and mean CST on OCT was 352.5 μm ± 128.5 μm. Only 11 (9.2%) eyes were dry on OCT at baseline: 39.5% had presence of IRF, 72.3% had presence of SRF, 41.2% had presence of intraretinal cysts, and 50.4% had presence of SRHM. After switching to faricimab, the eyes received a mean of 4.8 ± 2.7 faricimab injections up to the time of data cut-off. At last visit, the mean BCVA maintained at 60.3 ± 20.7 letter and mean CST reduction was - 41.6 μm (p < 0.001). Compared to baseline, 49 (41.2%) were dry on OCT: 24.4% had presence of IRF, 41.2% had presence of SRF, 29.4% had presence of intraretinal cysts, and 48.7% had presence of SRHM (all p < 0.001). No serious ocular adverse events were reported. Switching patients with nAMD to faricimab in real-world scenarios has demonstrated the ability to maintain vision while adding anatomical gains in those previously resistant to alternative anti-VEGF therapy. Faricimab is well-tolerated with no serious ocular adverse events reported.},
}
@article {pmid41020975,
year = {2025},
author = {Jonas, JB and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Gilemzianova, LI and Fakhretdinova, AA and Tuliakova, AM and Wang, YX and Xu, J and Nangia, V and Nangia, PV and Wu, S and Chen, S and Bi, H and Hu, Y and Qu, Y and Zhu, D and Wu, X and Jonas, RA and Panda-Jonas, S},
title = {Association between axial length and corneal refractive power in the two-continent population-based studies project.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41020975},
issn = {1435-702X},
abstract = {PURPOSE: To examine associations between corneal refractive power (CRP) and axial length (AL) in various populations of different ethnicities and age.<br><br>METHODS: Using biometry, we measured AL and CRP in population-based studies (Ural Eye and Medical Study (UEMS), Ural Very Old Study (UVOS), Beijing Eye Study (BES), Central India Eye and Medical Study (CIEMS), and Kailuan Eye Study (KES), all examining adults, and the Ural Children Eye Study (UCES), Shandong Children Eye Study (SCES) and Hinggan Children Eye Study (HCES), all examining schoolchildren).<br><br>RESULTS: In all studies examining adults, CRP significantly and linearly decreased with longer AL for the AL range from 21.0&#xa0;mm to 24.0&#xa0;mm (UEMS and UVOS) or 24.5&#xa0;mm (BES, CIEMS and KES). For an AL&#x2009;>&#x2009;24.0-24.5&#xa0;mm, CRP was statistically independent of AL (UEMS:P&#x2009;=&#x2009;0.38; UVOS:P&#x2009;=&#x2009;0.10), or increased with longer AL (BES:P&#x2009;=&#x2009;0.02; CIEMS:P&#x2009;<&#x2009;0.001). In the KES, CRP plateaued for an AL from 24.0&#xa0;mm to 26.5&#xa0;mm, and showed a decrease for an AL of 26.5&#x2009;+&#x2009;mm. In all studies on schoolchildren, CRP continuously decreased with longer AL across the whole range of AL, spanning from 21.0&#xa0;mm to 26.5&#x2009;+&#x2009;mm, with a steeper decrease for an AL between 21.0&#xa0;mm and 24.0&#xa0;mm than for an AL of 24.0&#x2009;+&#x2009;mm. For an AL of 24.0&#x2009;+&#x2009;mm, the CRP values were significantly (P&#x2009;>&#x2009;0.001) lower in all three schoolchildren studies than in the studies including adults.<br><br>CONCLUSIONS: Myopia varies between schoolchildren and adults in the relationship between AL and CRP, potentially pointing to a difference between entities.<br><br>KEY MESSAGES: What is&#xa0;known Corneal refractive power (CRP) is correlated with axial length. What is&#xa0;new In adults, CRP significantly and linearly decreased with longer axial length for the axial length range from 21.0mm to approximately 24.5mm, while for an axial length of >24.5mm, the CRP was statistically independent of axial length or increased with longer axial length. In schoolchildren, the CRP continuously decreased with longer axial length across the whole range of axial length, including the highly myopic part, with a steeper decrease in CRP for an axial length between 21.0mm and 24.0mm than for an axial length of 24.0+mm. These differences between myopia in schoolchildren and myopia in adults may give a hint that today&#xb4;s schoolchildren myopia may partially differ from the myopia of adults.},
}
@article {pmid41019872,
year = {2025},
author = {Chujo, S and Matsubara, H and Mase, Y and Muramoto, Y and Kato, K and Kondo, M},
title = {Comparisons of Early Changes of Vascular Structure After Treatment with Faricimab and Aflibercept in Eyes with Macular Neovascularization by OCT Angiography.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3527-3533},
pmid = {41019872},
issn = {1177-5467},
abstract = {OBJECTIVE: To evaluate whether Faricimab, which targets Ang-2, can reduce macular neovascularization (MNV) metrics on OCTA compared with Aflibercept in treatment-naïve nAMD.<br><br>METHODS: Among 34 eyes treated with Aflibercept, 12 eyes were included; among 31 eyes treated with Faricimab, 14 eyes were included. Vessel area (Va) and junction density (JD) were measured using AngioTool over a 3-month loading period.<br><br>RESULTS: In the Faricimab group, mean Va changed from 0.14 mm[2] at baseline to 0.15 mm[2] at 3 months; JD changed from 0.16 to 0.15/mm. In the Aflibercept group, Va decreased from 0.29 to 0.20 mm[2], and JD changed from 0.77 to 0.83/mm. Differences in Va and JD between groups were not statistically significant.<br><br>CONCLUSION: There were no significant structural changes in MNV with either drug over the short term. These findings suggest that vascular effects of Faricimab may require longer observation to become evident.},
}
@article {pmid41019493,
year = {2025},
author = {Chee, PL and Hao, M and Liu, G and Yew, PYM and Kim, E and Liu, H and Sathasivam, T and Xu, G and Liu, Z and Kai, D},
title = {Functional scaffolds design strategies for retinal repair and regeneration.},
journal = {Materials today. Bio},
volume = {35},
number = {},
pages = {102283},
pmid = {41019493},
issn = {2590-0064},
abstract = {The growing strain placed on both society and the healthcare system due to an ageing population should not be underestimated. Age-related macular degeneration (AMD) is a leading cause of blindness worldwide and is projected to affect 288 million people globally by 2040. Current treatment options for AMD primarily focus on disease management rather than offering a definitive cure. Retinal tissue engineering, which aims to develop targeted regenerative strategies to restore or replace damaged retinal tissues, offers pioneering advances that could provide curative solutions for AMD and revolutionize its therapeutic landscape. This review aims to provide a comprehensive overview of biomaterial strategies for retinal repair and regeneration, with a particular focus on scaffold design. To effectively address the underlying causes of retinal degenerative diseases and develop functional scaffolds, the review examines the retinal anatomy, the vision-impairing diseases associated with degeneration and relevant cell types. Building on this foundation, it further discusses various scaffold design strategies, including the selection of biomaterials, the structural and mechanical mimicry of native tissues, and the fabrication of scaffolds for co-culturing. Beyond current strategies, we also explore potential features, such as electrically conductive and photo-responsiveness, that could shape the future of scaffold design in retina tissue engineering. Collectively, these insights provide a robust framework to drive and accelerate the next generation of scaffold development for retinal tissue engineering.},
}
@article {pmid41018360,
year = {2025},
author = {Flindris, K and Chatzipetrou, C and Papafotiou, E and Kaliardas, A and Koumpoulis, I and Melissourgos, I},
title = {Quality of Life and Treatment Satisfaction in Patients Receiving Intravitreal Injection Therapy for Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Retinal Vein Occlusion: A Cross-Sectional Study.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e91004},
pmid = {41018360},
issn = {2168-8184},
abstract = {Purpose Neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) are leading causes of vision loss treated with intravitreal injections. The impact of these chronic treatments on patients' vision-related quality of life (QoL) and treatment satisfaction (TS) across different diseases remains unclear. This study aims to evaluate and compare vision-related QoL and TS in patients with nAMD, DME, or RVO undergoing intravitreal therapy, and to identify factors associated with QoL. Methods Single-center cross-sectional study including 88 patients (58 with nAMD, 22 DME, 8 RVO) receiving intravitreal anti-vascular endothelial growth factor (VEGF) or corticosteroid injections (≥3 prior injections). Vision-related QoL was assessed with the National Eye Institute Visual Function Questionnaire-25 (VFQ-25), and TS was measured with the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ). Best-corrected visual acuity (BCVA) of both eyes was measured (logMAR), and a complete ophthalmological examination was performed. We compared VFQ-25 and MacTSQ scores among diagnostic groups and analyzed correlations between QoL, TS, and systemic factors. Multivariable linear regression identified independent predictors of QoL. Results Mean VFQ-25 composite score was 65.1 ± 20.7 (out of 100), indicating moderate QoL impairment, with no significant difference between nAMD, DME, and RVO groups (p = 0.40). Mean MacTSQ score was 81.9 ± 13.5, reflecting high treatment satisfaction, also with no difference among diagnoses (p = 0.14). Worse BCVA (higher mean logMAR of both eyes) and older age were each significantly associated with lower QoL (Spearman r ≈ -0.50 and r ≈ -0.48; p < 0.001). In multivariable analysis, older age (p = 0.004), presence of dyslipidemia (p = 0.03) or depression (p = 0.04), and worse BCVA (p < 0.001) were independent predictors of lower VFQ-25 scores. Diagnostic group, bilateral treatment, and other comorbidities were not independent predictors of QoL. Treatment satisfaction was uniformly high across all groups and was not significantly correlated with age or QoL. Conclusions Patients with nAMD, DME, and RVO receiving intravitreal injections report similar levels of vision-specific QoL impairment and high satisfaction with treatment. Preservation of visual acuity is the key determinant of better QoL, underscoring the importance of effective therapy and adherence. Additionally, older age and systemic factors such as dyslipidemia and depression adversely affect QoL, highlighting the need for a multidisciplinary management approach. These findings suggest that regardless of retinal disease etiology, maintaining vision and addressing comorbidities are critical to optimizing patient-centered outcomes.},
}
@article {pmid41018263,
year = {2025},
author = {Gu, X and Zhou, Y and Zhao, J and Zhang, H and Pan, X and Li, B and Zhang, B and Wang, Y and Xia, S and Lin, H and Wang, J and Ding, D and Li, X and Wu, S and Yang, J and Chen, Y},
title = {Diagnostic performance and generalizability of deep learning for multiple retinal diseases using bimodal imaging of fundus photography and optical coherence tomography.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1665173},
pmid = {41018263},
issn = {2296-634X},
abstract = {PURPOSE: To develop and evaluate deep learning (DL) models for detecting multiple retinal diseases using bimodal imaging of color fundus photography (CFP) and optical coherence tomography (OCT), assessing diagnostic performance and generalizability.<br><br>METHODS: This cross-sectional study utilized 1445 CFP-OCT pairs from 1,029 patients across three hospitals. Five bimodal models developed, and the model with best performance (Fusion-MIL) was tested and compared with CFP-MIL and OCT-MIL. Models were trained on 710 pairs (Maestro device), validated on 241, and tested on 255 (dataset 1). Additional tests used different devices and scanning patterns: 88 pairs (dataset 2, DRI-OCT), 91 (dataset 3, DRI-OCT), 60 (dataset 4, Visucam/VG200 OCT). Seven retinal conditions, including normal, diabetic retinopathy, dry and wet age-related macular degeneration, pathologic myopia (PM), epiretinal membran, and macular edema, were assessed. PM ATN (atrophy, traction, neovascularization) classification was trained and tested on another 1,184 pairs. Area under receiver operating characteristic curve (AUC) was calculated to evaluated the performance.<br><br>RESULTS: Fusion-MIL achieved mean AUC 0.985 (95% CI 0.971-0.999) in dataset 2, outperforming CFP-MIL (0.876, P < 0.001) and OCT-MIL (0.982, P = 0.337), as well as in dataset 3 (0.978 vs. 0.913, P < 0.001 and 0.962, P = 0.025) and dataset 4 (0.962 vs. 0.962, P < 0.001 and 0.962, P = 0.079). Fusion-MIL also achieved superior accuracy. In ATN classification, AUC ranges 0.902-0.997 for atrophy, 0.869-0.982 for traction, and 0.742-0.976 for neovascularization.<br><br>CONCLUSION: Bimodal Fusion-MIL improved diagnosis over single-modal models, showing strong generalizability across devices and detailed grading ability, valuable for various scenarios.},
}
@article {pmid41017685,
year = {2025},
author = {Yang, Y and Lv, M and Qiao, B and Yang, Z and Zhang, H and Wu, Z and Xia, Y and Yao, D and Chen, K},
title = {Retinitis pigmentosa elicits neurodegeneration within the visual pathway in REEP6 knockout mice.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-00168},
pmid = {41017685},
issn = {1673-5374},
abstract = {While degenerative diseases of the central nervous system are commonly linked to age-related macular degeneration and glaucoma, they have also been infrequently associated with retinitis pigmentosa, a condition defined by retinal degeneration that can be caused by an isoform of receptor expression enhancing protein 6 (REEP6) expressed in rod photoreceptors. In this study, we used REEP6 knockout mice (REEP6-/-) and wild-type mice (REEP6+/+) to examine neurodegenerative pathology within the visual pathways and neural activity in the primary visual cortex (V1) at three specific time points (1, 6, and 10 months) during retinitis pigmentosa progression. Microglial activation was observed in both the retina and the primary visual cortex starting at 1 month of age, but no such activation was detected in the lateral geniculate nucleus at any time point. Not only was increased microglial activation observed at 6 and 10 months within the primary visual cortex of REEP6-/- mice, but also coinciding with elevated levels of phosphorylated Tau expression. At 6 and 10 months of age, primary visual cortex neurons in REEP6-/- mice exhibited reduced responses to grating stimuli and increased spontaneous activity compared with neurons in the primary visual cortex of mice in the control group. Our findings show that retinitis pigmentosa induces neurodegenerative pathology within the visual pathway of mice, particularly in the primary visual cortex, suggesting that ocular disease contributes substantially to central nervous system degeneration. It may provide new clues for the selection of treatment opportunities and the development of therapeutic measures for the subsequent treatment of retinitis pigmentosa or even other retinal degenerative diseases.},
}
@article {pmid41017154,
year = {2025},
author = {Ebner, LJA and Imsand, C and Karademir, D and Peters, F and Kiessling, E and Fottner, A and Matter, C and Fajardo, DS and Merolla, L and Wögenstein, GM and Tsioti, I and Govers, LP and Blaser, F and Meneau, I and Boye, SL and Boye, SE and Grimm, C and Samardzija, M},
title = {A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2025.09.044},
pmid = {41017154},
issn = {1525-0024},
abstract = {Age-related tissue changes lead to reduced oxygen delivery to photoreceptors and the retinal pigment epithelium (RPE) and contribute to the pathology of age-related macular degeneration (AMD). The implication of hypoxia-inducible factors (HIFs) in this process makes them good candidates as therapeutic targets for AMD. We developed a multiplex dual-acting therapy utilizing the shRNAmir system, delivered by a single adeno-associated virus, that reduces mRNA levels of Hif1a in photoreceptors and Hif2a in the RPE. This RNA interference (RNAi)-based strategy demonstrated a strong therapeutic effect, potently preserving photoreceptors and the RPE in two models of pseudo- and true hypoxia up to 61 weeks post-injection. The efficacy of our dual-acting virus proved superior to single-acting viruses targeting only Hif1a in photoreceptors or Hif2a in the RPE. By targeting a common, conserved disease pathway, this gene-agnostic RNAi therapy shows significant potential to protect tissues from chronic hypoxic insults in complex diseases such as AMD.},
}
@article {pmid41016648,
year = {2025},
author = {Yin, X and Shi, P and Ge, J},
title = {Analysis of clinical characteristics of multifocal electroretinogram and microperimetry in patients with high myopia.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {56},
number = {},
pages = {105237},
doi = {10.1016/j.pdpdt.2025.105237},
pmid = {41016648},
issn = {1873-1597},
abstract = {To investigate the role of microperimetry (MP) and multifocal electroretinogram (mfERG) in evaluating macular function in high myopia METHODS: From January to June 2025, data from 42 patients (76 eyes) undergoing both MP and mfERG at Jinan Mingshui Eye Hospital were retrospectively analyzed. The impact of axial length, atrophic macular degeneration (Atrophic, Tractional, Neovascular, ATN) grade, and age on the results was compared RESULTS: MP and mfERG results in pathological myopia were significantly lower than the normal range. Significant differences in light sensitivity and best-corrected visual acuity (BCVA) were found across different axial lengths, ATN grades, and age groups (P < 0.05). For amplitude density, Ring3 and Ring4 showed significant differences among axial lengths (P < 0.05), while Rings 1-5 exhibited significant differences among ATN grades and age groups (P < 0.05). Further clarification is needed for latency differences among these variables CONCLUSION: MP and mfERG are valuable tools for assessing macular function changes in high myopia.},
}
@article {pmid41016571,
year = {2025},
author = {Kao, CC and Chokkalingam, U and Singh, A and Shih, PC and Prakash, E and Wang, JS},
title = {Protective effects of acemannan-enriched Aloe polysaccharide J2 against UVA-induced autophagic cell death in retinal pigment epithelial cells.},
journal = {European journal of pharmacology},
volume = {1006},
number = {},
pages = {178199},
doi = {10.1016/j.ejphar.2025.178199},
pmid = {41016571},
issn = {1879-0712},
mesh = {*Ultraviolet Rays/adverse effects ; *Retinal Pigment Epithelium/cytology/drug effects/radiation effects/metabolism/pathology ; Humans ; *Aloe/chemistry ; *Autophagy/drug effects/radiation effects ; Reactive Oxygen Species/metabolism ; *Mannans/pharmacology ; Cell Line ; *Polysaccharides/pharmacology ; Cytoprotection/drug effects/radiation effects ; Mitogen-Activated Protein Kinases/metabolism ; },
abstract = {Age-Related Macular Degeneration (AMD) is one of the leading causes of irreversible vision loss worldwide, characterized by the degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells, resulting in progressive loss of central vision. RPE cells are highly specialized and essential for retinal function, and their malfunction due to genetic, environmental, or age-related factors contributes significantly to AMD pathogenesis. Ultraviolet A (UVA) radiation is recognized as a major causative factor, as it induces the accumulation of reactive oxygen species (ROS) in RPE cells, ultimately contributing to the development of AMD. On the other hand, acemannan, a D-isomer mucopolysaccharide derived from Aloe vera pulp, is known for its antioxidant and anti-inflammatory properties. In this study, we extracted a highly purified Aloe-derived polysaccharide fraction enriched in acemannan, designated Aloe polysaccharide J2 (ACJ2), to investigate its protective effects against UVA-induced RPE damage. The results showed that post-treatment with ACJ2 significantly reduced UVA-induced cell death by lowering mitochondrial ROS levels, suppressing phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK), and downregulating proinflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and inducible nitric oxide synthase (iNOS). Furthermore, ACJ2 enhanced heme oxygenase-1 (HO-1) expression and mitochondrial DNA levels, and inhibited p62/sequestosome-1 (p62) consumption and microtubule-associated protein 1 light chain 3 (LC3)-I/II conversion, thereby reducing autophagic flux. These findings demonstrate that ACJ2 mitigates UVA-induced damage and restores disrupted autophagy in RPE cells, supporting its potential as a therapeutic candidate for AMD.},
}
@article {pmid41016543,
year = {2026},
author = {Jiang, GC and Pan, HY and Gu, L and Cheng, TT and Zhu, BX and Wang, XQ and Yu, JY and Zhu, F and Lin, M and Hu, JN and Wang, XW},
title = {Chrysanthemum morifolium extract attenuates pathological angiogenesis of age-related macular degeneration via VEGF and Nrf2 pathway modulation.},
journal = {Journal of ethnopharmacology},
volume = {355},
number = {Pt B},
pages = {120660},
doi = {10.1016/j.jep.2025.120660},
pmid = {41016543},
issn = {1872-7573},
mesh = {Animals ; *Chrysanthemum/chemistry ; Humans ; *NF-E2-Related Factor 2/metabolism ; *Vascular Endothelial Growth Factor A/metabolism ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Plant Extracts/pharmacology/therapeutic use ; Zebrafish ; Human Umbilical Vein Endothelial Cells/drug effects ; Signal Transduction/drug effects ; Rats ; Oxidative Stress/drug effects ; *Angiogenesis Inhibitors/pharmacology/isolation &amp; purification/therapeutic use ; Cell Line ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Male ; Rats, Sprague-Dawley ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Retinal Pigment Epithelium/drug effects ; Cell Movement/drug effects ; Neovascularization, Pathologic/drug therapy ; },
abstract = {Chrysanthemum morifolium has long been utilized in Traditional Chinese Medicine to improve visual acuity and alleviate ocular damage. Although recent pharmacological studies highlight its antioxidant and vasoprotective effects, its efficacy against neovascular processes in age-related macular degeneration (AMD) has not been established.<br><br>AIM OF THE STUDY: This study aimed to investigate the therapeutic potential and underlying mechanisms of Chrysanthemum morifolium extract (CME) in managing neovascular AMD, emphasizing its effects on vascular endothelial growth factor (VEGF)-mediated angiogenesis and oxidative stress regulation.<br><br>MATERIALS AND METHODS: In vitro, ARPE-19 human retinal pigment epithelial cells underwent hypoxic and oxidative stress assays to measure VEGF, hypoxia-inducible factor 1-alpha (HIF-1&#x3b1;), and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Human umbilical vein endothelial cells (HUVECs) were treated with a conditioned medium (CM) from CME-exposed ARPE-19&#xa0;cells to assess migration, invasion, and tube formation. In vivo therapeutic efficacy was validated in cobalt chloride (CoCl2)-induced zebrafish and laser-induced rat choroidal neovascularization (CNV) models.<br><br>RESULTS: CME significantly attenuated hypoxia- and CoCl2-induced upregulation of VEGF and HIF-1&#x3b1;, enhanced Nrf2 signaling, and reduced reactive oxygen species (ROS) in ARPE-19&#xa0;cells. CME-CM markedly suppressed HUVEC migration, invasion, and angiogenesis. In zebrafish and rat CNV models, CME treatment significantly reduced neovascular lesion area and preserved retinal architecture in a dose-dependent manner, without evident toxicity.<br><br>CONCLUSIONS: CME exerts dual anti-angiogenic and antioxidant effects in AMD models by simultaneously targeting VEGF-driven angiogenesis and oxidative stress, supporting its therapeutic potential as a safe and effective herbal intervention for neovascular AMD.},
}
@article {pmid41011040,
year = {2025},
author = {Preiksaitiene, E and Gurskytė, V and Mikštienė, V and Strupaitė-Šileikienė, R and Dzindzalieta, R and Petraitytė, G and Dapkūnas, J and Vyčaitė, E and Karčiauskaitė, D and Černiauskas, L and Utkus, A},
title = {Evidence for the Pathogenicity of a CFH Variant in a Multigenerational Family with Cuticular Drusen.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {9},
pages = {},
pmid = {41011040},
issn = {1648-9144},
support = {No. 02-002-P-0001//Economic Revitali-435 zation and Resilience Enhancement Plan "New Generation Lithuania"/ ; },
mesh = {Humans ; Female ; Male ; *Retinal Drusen/genetics/physiopathology ; Middle Aged ; *Complement Factor H/genetics/analysis ; Pedigree ; Adult ; Tomography, Optical Coherence/methods ; Aged ; Exome Sequencing/methods ; Macular Degeneration/genetics ; Extended Family ; Eye Diseases, Hereditary ; Bruch Membrane/pathology ; },
abstract = {Background and Objectives: Cuticular drusen are a rare form of early-onset drusen maculopathy, which falls within the spectrum of age-related macular degeneration. Previous research suggests that cuticular drusen can result from monogenic inheritance of pathogenic variants in the complement factor H coding CFH gene. These variants impair regulation of the alternative complement pathway, leading to increased central retinal inflammation, progressive tissue damage, and ultimately, vision loss. This study aims to assess the pathogenic potential of the variant NM_000186.4(CFH):c.1318C>T, previously classified as a variant of unknown significance. Materials and Methods: Eight individuals from three generations of a single family underwent ophthalmologic evaluation, including biomicroscopy, ophthalmoscopy, optical coherence tomography, and optical coherence tomography angiography. Subsequently, whole-exome sequencing of the proband's DNA sample was performed. Sanger sequencing was used to validate the whole-exome sequencing results and to assess segregation of the identified variant in the family. The individuals' clinical, instrumental, and genetic data were collected and stored in the database iGENLIT. Results: the heterozygous NM_000186.4(CFH):c.1318C>T variant was detected in six family members. Of these, five have been clinically diagnosed with cuticular drusen. Three affected individuals are currently in their 40s and maintain good visual acuity. In two family members, the drusen progressed to choroidal neovascularization, fibrosis, and atrophy, resulting in profound visual loss at the ages of 54 and 62. One 21-year-old individual also carries the variant, but currently shows no evidence of drusen, likely due to age. Conclusion: In this study, we demonstrated a genotype-phenotype relationship in individuals with the NM_000186.4(CFH):c.1318C>T variant, which suggests its pathogenic role in the development of cuticular drusen and associated complications.},
}
@article {pmid41010841,
year = {2025},
author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S},
title = {Impact of Punctate Hyperfluorescence Status on Treatment Outcomes of Faricimab Versus Aflibercept in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {18},
pages = {},
pmid = {41010841},
issn = {2077-0383},
abstract = {Background/Objectives: To compare the treatment outcomes of intravitreal faricimab (IVF) and intravitreal aflibercept (IVA) in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), stratified by the presence or absence of punctate hyperfluorescence (PH). Methods: This retrospective study included 301 treatment-naïve patients with nAMD who underwent either IVF or IVA. After 1:1 propensity score matching based on baseline best-corrected visual acuity (BCVA), age, and PH status, 56 eyes (28 per group) were analyzed within each PH subgroup. Outcome measures included BCVA, central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and no retinal fluid rate during the loading dose regimen, and the retreatment rate after the loading dose regimen. The prespecified primary endpoint was the 1-year retreatment rate after completion of the loading dose regimen, analyzed by Kaplan-Meier curves with log-rank tests. Comparisons were performed separately between the PH and non-PH groups. Results: In the PH group, no significant differences were observed between IVF and IVA groups in terms of BCVA, CRT, SFCT, no retinal fluid rate, or retreatment rate at any time point. In the non-PH group, IVF and IVA groups showed no significant differences in BCVA, CRT, or SFCT at any time point; however, the IVF group achieved a significantly higher no retinal fluid rate (100.0% vs. 64.3%, p < 0.001) and a lower retreatment rate at 1 year (71.4% vs. 92.9%, p = 0.004) than the IVA group. Conclusions: IVF and IVA showed comparable efficacy in nAMD with PH. In contrast, IVF demonstrated superior anatomical outcomes in nAMD without PH. These retrospective findings suggest distinct pathophysiological mechanisms between PH and non-PH subtypes.},
}
@article {pmid41010701,
year = {2025},
author = {López-Cuenca, I and Fabozzi, L and Younis, S and Ali, A and Ramírez, JM and Cordeiro, MF and Hoz, R},
title = {The Effects of the COVID-19 Pandemic on the Follow-Up of Patients with Age-Related Macular Degeneration in a Tertiary Hospital in London, the UK.},
journal = {Journal of clinical medicine},
volume = {14},
number = {18},
pages = {},
pmid = {41010701},
issn = {2077-0383},
support = {CT42/18//Universidad Complutense de Madrid/ ; },
abstract = {Background/Objectives: Adherence to medical appointments is crucial for managing age-related macular degeneration (AMD). The COVID-19 pandemic disrupted healthcare services, potentially affecting disease control. This study aimed to assess the impact of the pandemic on appointment adherence and disease progression in AMD patients at the Western Eye Hospital in London. Methods: Patients were divided into two groups: those who attended appointments on time and those who experienced delays (n = 100 per group). We compared disease progression using demographic data, best-corrected visual acuity (BCVA), and macular thickness measured by OCT, extracted from medical records. Results: In patients without delays, BCVA remained stable pre- and post-COVID-19, although significant changes in macular thickness were observed in the central (C0), superior (S1, S2), nasal (N1), and inferior (I1, I2) macular sectors. In contrast, patients with delayed appointments showed a significant increase in N1 macular thickness from 324.00 (304.00-358.00) pre-COVID-19 to 337.50 (305.50-375.50) post-COVID-19 (p = 0.030). Post-COVID-19, patients without delays had significantly better BCVA and thinner N1 macular thickness than those with delays. A positive correlation was found between the length of appointment delays and increased macular thickness in S1 and I2 sectors. Conclusions: Timely follow-up is essential in AMD management. Appointment delays during the COVID-19 pandemic were associated with increased macular thickness and worse visual outcomes, highlighting the importance of maintaining continuity of care even during healthcare disruptions.},
}
@article {pmid41010580,
year = {2025},
author = {Moon, GY and Park, JS and Bae, KW},
title = {Optical Coherence Tomography- and Optical Coherence Tomography Angiography-Based Evaluation in Treatment-Naïve Non-Exudative Macular Neovascularization.},
journal = {Journal of clinical medicine},
volume = {14},
number = {18},
pages = {},
pmid = {41010580},
issn = {2077-0383},
support = {2024-0109//Eulji University/ ; },
abstract = {Background/Objectives: We evaluated the clinical features and natural course of treatment-naïve non-exudative macular neovascularization (NE MNV) associated with age-related macular degeneration in Korean patients. Methods: This retrospective longitudinal study of 21 eyes of 21 patients with NE MNV involved a chart review of best corrected visual acuity (BCVA), optical coherence tomography (OCT), and OCT angiography parameters. Results: This study included 13 men (13/21, 61.9%) and 8 women (8/21, 38.1%), with a mean age of 71.5 ± 9.1 years. The average follow-up period was 15.1 ± 11.8 (range 6.0-49.6) months, and 14 eyes (66.7%) demonstrated exudative changes on OCT scans. The baseline BCVA was 0.15 ± 0.18 logMAR. The initial central macular thickness (CMT), subfoveal choroidal thickness, and the outer retinal layer thickness were 265.3 ± 37.1, 245.2 ± 95.2, and 86.6 ± 5.3 μm, respectively. Cox proportional hazards analysis revealed that older age (hazard ratio [HR]: 1.096, 95% confidence interval [CI]: 1.002-1.200; p = 0.045), larger baseline CMT (HR: 1.025, 95% CI: 1.002-1.049; p = 0.035), and larger baseline MNV (HR: 1.618, 95% CI: 1.035-2.529; p = 0.035) were significant risk factors for exudative changes. Conclusions: We observed the clinical features and natural course of NE MNV in Korean patients and identified that significant risk factors for exudative changes in NE MNV included old age, initially thick CMT, and larger MNV size at baseline. For eyes with NE MNV that have risk factors of exudative conversion, more frequent observation is recommended to ensure the appropriate management.},
}
@article {pmid41010531,
year = {2025},
author = {Li, C and Wu, J and Zhao, Y and Zhu, J and Zhu, X and Chen, Y and Wu, J},
title = {Identification of Amino Acids That Regulate Angiogenesis and Alter Pathogenesis of a Mouse Model of Choroidal Neovascularization.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
pmid = {41010531},
issn = {2072-6643},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/etiology/pathology ; Activating Transcription Factor 4/metabolism/genetics ; Disease Models, Animal ; Humans ; *Amino Acids/metabolism ; Mice ; Vascular Endothelial Growth Factor A/metabolism ; Endothelial Cells/metabolism ; Mice, Inbred C57BL ; Signal Transduction ; Protein Serine-Threonine Kinases/metabolism/genetics ; Eukaryotic Initiation Factor-2/metabolism ; Angiogenesis ; },
abstract = {Background: Metabolic stress from amino acid (AA) insufficiency is increasingly linked to pathological angiogenesis, but specific essential AA (EAA) roles remain undefined. Neovascular age-related macular degeneration (AMD), a major cause of blindness driven by aberrant ocular neovascularization, has limited efficacy with current VEGFA-targeting therapies. We sought to identify specific EAAs that regulate pathological angiogenesis and dissect their mechanisms to propose new therapeutic strategies. Methods: Human retinal microvascular endothelial cells (HRMVECs) were used to identify angiogenesis-regulating amino acids through systematic EAA screening. The molecular mechanism was investigated using shRNA-mediated knockdown of key stress response regulators (HRI, PKR, PERK, GCN2) and ATF4. Angiogenesis was assessed via tubule formation and migration assays. Therapeutic potential was examined in a laser-induced choroidal neovascularization (CNV) mouse model, evaluated by fluorescein angiography and histomorphometry. Results: Deprivation of methionine, lysine, and threonine potently induced capillary-like tube formation (p < 0.01). Mechanistically, restriction of these three EAAs activated HRI and GCN2 kinases, converging on eIF2α phosphorylation to induce ATF4 and its target VEGFA. Dual, but not single, knockdown of HRI and GCN2 abolished eIF2α-ATF4 signaling and angiogenic responses. Restricting these EAAs exacerbated CNV area in mice. Conclusions: Our findings reveal a coordinated HRI/GCN2-ATF4-VEGFA axis linking EAA scarcity to vascular remodeling, establishing proof-of-concept for targeting this pathway in CNV. This work highlights the therapeutic potential of modulating specific AA availability or targeting the HRI/GCN2-ATF4 axis to treat CNV.},
}
@article {pmid41010490,
year = {2025},
author = {Naquin, ER and Garg, R and Chen, WJ and Karmakar, E and Prasad, A and Mandadi, S and Depala, K and Gopianand, JS and Gnana-Prakasam, JP},
title = {Iron: More than Meets the Eye.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
pmid = {41010490},
issn = {2072-6643},
support = {R01 EY031008/EY/NEI NIH HHS/United States ; 1R01EY031008-05/NH/NIH HHS/United States ; },
mesh = {Humans ; *Iron/metabolism ; *Iron Overload/complications/metabolism ; *Eye Diseases/etiology/metabolism ; Oxidative Stress ; Homeostasis ; Iron Deficiencies ; Animals ; Dietary Supplements ; *Eye/metabolism ; },
abstract = {Iron is an essential micronutrient integral to ocular physiology, supporting biochemical processes such as mitochondrial respiration, DNA synthesis and phototransduction. Disruptions in systemic or local iron homeostasis, whether due to overload or deficiency, have been increasingly implicated in the pathogenesis of a broad range of anterior and posterior segment ocular disorders. Iron deficiency may compromise retinal bioenergetics, impair cellular repair, and increase susceptibility to oxidative stress, while iron overload facilitates the generation of reactive oxygen species, contributing to lipid peroxidation, mitochondrial dysfunction, and ferroptosis. Dysregulated iron metabolism has been associated with several ocular pathologies, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinal detachment, cataracts, and anemic retinopathy. The eye possesses specialized iron regulatory mechanisms involving proteins such as transferrin, ferritin, ferroportin, and hepcidin that govern iron transport, storage, and export across ocular barriers. Aberrations in these pathways are now recognized as contributing factors in disease progression. This narrative review explores the complex dual role of iron overload and deficiency in ocular diseases. It highlights the molecular mechanisms underlying iron-mediated pathologies in both the posterior and anterior segments of the eye, along with the clinical manifestations of iron imbalance. Current therapeutic approaches are discussed, including oral and parenteral iron supplementation for deficiency and emerging chelation-based or antioxidant strategies to address iron overload, while highlighting their limitations. Key challenges remain in developing targeted ocular delivery systems that optimize bioavailability and minimize systemic toxicity. Hence, maintaining iron homeostasis is critical for visual function, and further research is needed to refine therapeutic interventions and clarify the mechanistic role of iron in ocular health and disease.},
}
@article {pmid41010482,
year = {2025},
author = {Ayoub, G},
title = {Vitamins, Vascular Health and Disease.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
pmid = {41010482},
issn = {2072-6643},
mesh = {Humans ; Folic Acid/administration &amp; dosage ; Dietary Supplements ; *Vascular Diseases/prevention &amp; control ; *Vitamins/administration &amp; dosage ; Hyperhomocysteinemia/prevention &amp; control ; *Endothelium, Vascular/drug effects/physiopathology ; Tetrahydrofolates/administration &amp; dosage ; Vitamin B Complex ; },
abstract = {Vascular health relies on the proper function of endothelial cells, which regulate vascular tone, blood fluidity, and barrier integrity. Endothelial dysfunction, often aggravated by inadequate vitamin absorption, contributes to a spectrum of clinical disorders, including cardiovascular disease, cerebrovascular disease, peripheral artery disease, age-related macular degeneration, lymphedema, and chronic venous insufficiency. B-group vitamins (especially folate, or vitamin B9), along with vitamins B12, B6, C, D, and E, are essential in maintaining endothelial function, supporting DNA synthesis, regulating methylation, enhancing cellular repair, mitigating oxidative stress and inflammatory signaling, and curtailing vascular damage. Folate is noted for its central function in one-carbon metabolism and in converting homocysteine to methionine, thereby reducing vascular toxicity. We cover natural dietary sources of folate, synthetic folic acid, and the biologically active forms 5-methyl-(6S)-tetrahydrofolate (L-5-MTHF, L-methylfolate) and 5-formyl-(6S)-tetrahydrofolate (levoleucovorin). Therapeutic strategies to address vascular health and prevent hyperhomocysteinemia in order to preclude follow-on disorders include targeted vitamin supplementation, dietary improvements to ensure a sufficient intake of bioavailable nutrient forms, and, in certain clinical contexts, the use of active L-methylfolate or levoleucovorin (a drug product) to bypass metabolic conversion issues. These evidence-based interventions aim to restore endothelial homeostasis, slow disease progression, and improve patient outcomes across a variety of disorders linked to poor vascular health.},
}
@article {pmid41010227,
year = {2025},
author = {Guo, R and Zhang, X and Song, Y and Shen, J and Li, K and Zheng, Y},
title = {Surface Modification and Pore Size Regulation of MSN as Function Aflibercept Carrier for Anti-Vascular Migration.},
journal = {Materials (Basel, Switzerland)},
volume = {18},
number = {18},
pages = {},
pmid = {41010227},
issn = {1996-1944},
support = {ZHY10-Z73//Heilongjiang Province Traditional Chinese Medicine Research Project/ ; },
abstract = {Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness in the elderly, primarily by choroidal neovascularization (CNV) leakage. While intravitreal injections of anti-angiogenic antibodies (e.g., aflibercept) provide clinical benefits, their short half-life necessitates frequent administrations, potentially causing ocular infections or retinal detachment. There is an urgent need for effective antibody delivery systems. Mesoporous silica nanoparticles (MSN) have emerged as promising nanocarriers due to their tunable porosity, surface modifiability, and biocompatibility, though their application in ophthalmology for antibody delivery remains underexplored. We developed two MSN carries: spiky mesoporous silica nanospheres (S-MSN) without amino groups and amine-functionalized hollow dendritic mesoporous silica nanospheres (A-HDMSN). Characterization revealed that A-HDMSN exhibited superior properties, including a larger surface area (550.32 vs. 257.72 m[2]/g), larger mesoporous pore size (17 vs. <10 nm), and 5.28 times higher drug loading capacity (286.31 ± 8.14 vs. 54.26 ± 3.61 μg/mg) compared to S-MSN (n = 3, p < 0.001), attributable to pore size effects and hydrogen bonding. FITC-labeled A-HDMSN demonstrated efficient uptake by retinal pigment epithelial cells (ARPE-19). Notably, A-HDMSN loaded with Aflibercept (A-HDMSN@Afl) showed significant inhibitory effect on VEGF-induced cell migration even 10 days after drug release in vitro, indicating a favorable sustained-release effect of the drug. These findings highlight A-HDMSN as a promising antibody delivery platform that could extend clinical dosing intervals, offering potential for improved AMD management.},
}
@article {pmid41008593,
year = {2025},
author = {Grenga, PL and Ciancimino, C and Meduri, A and Fragiotta, S},
title = {Optogenetics: A Novel Therapeutic Avenue for Age-Related Macular Degeneration.},
journal = {Biomolecules},
volume = {15},
number = {9},
pages = {},
pmid = {41008593},
issn = {2218-273X},
mesh = {Humans ; *Optogenetics/methods ; *Macular Degeneration/therapy/genetics/metabolism/pathology ; Animals ; Genetic Therapy/methods ; Dependovirus/genetics ; Retinal Pigment Epithelium/metabolism/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, characterized by progressive degeneration of the retinal pigment epithelium (RPE) and photoreceptors in the macula. Current treatment options primarily focus on slowing disease progression in neovascular AMD, while effective therapies for dry AMD remain limited. Optogenetics, a revolutionary technique utilizing light-sensitive proteins (opsins) to control the activity of genetically targeted cells, has emerged as a promising therapeutic strategy for restoring vision in retinal degenerative diseases. In retinal disease models, adeno-associated viruses (AAVs) serve as delivery vectors via intravitreal or subretinal injections. This review explores the principles of optogenetics, its application in preclinical AMD models, and the potential for clinical translation of this approach. We discuss the various optogenetic tools, delivery methods, and the challenges and future directions in harnessing this technology to combat AMD-related vision loss.},
}
@article {pmid41008535,
year = {2025},
author = {Stathopoulos, A and Wang, JJ and Martin, SF and Zhang, SX},
title = {Transmembrane Protein 97 (TMEM97): Molecular Target and Treatment in Age-Related Macular Degeneration (AMD).},
journal = {Biomolecules},
volume = {15},
number = {9},
pages = {},
pmid = {41008535},
issn = {2218-273X},
support = {R01 EY019949/EY/NEI NIH HHS/United States ; R01 EY036132/EY/NEI NIH HHS/United States ; R01 EY030970/EY/NEI NIH HHS/United States ; R21 EY035810/EY/NEI NIH HHS/United States ; EY019949, EY030970, EY035810, and EY036132//NIH/NEI/ ; },
mesh = {Humans ; *Macular Degeneration/metabolism/drug therapy/genetics/pathology ; Animals ; *Membrane Proteins/metabolism/genetics ; Molecular Targeted Therapy ; Retinal Pigment Epithelium/metabolism/pathology ; Oxidative Stress ; *Receptors, sigma/metabolism/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a common eye disease that significantly affects daily activities and impedes the quality of life in aging adults, yet effective treatments to halt or reverse disease progression are currently lacking. Ongoing research aims at understanding the complex mechanisms underlying AMD pathophysiology involving retinal pigment epithelium (RPE) dysfunction, drusen formation, inflammation, neovascularization, and RPE/photoreceptor degeneration. Sigma 2 receptor/transmembrane protein 97 (σ2R/TMEM97) is a multifunctional protein implicated in cellular processes including cholesterol homeostasis, lysosome-dependent autophagy, calcium homeostasis, and integrated stress response (ISR). Recent genome-wide association studies (GWASs) have identified σ2R/TMEM97 as a novel genetic risk factor strongly associated with AMD development. In this review, we summarize recent research progress on σ2R/TMEM97 in age-related neurodegenerative diseases, highlighting its implication as a molecular target in AMD via regulating oxidative stress, inflammation, lipid uptake, drusen formation, and epithelial-mesenchymal transition (EMT). We also discuss the potential of modulating σ2R/TMEM97 function with novel small-molecule drugs as a promising treatment for dry AMD and the unresolved questions in understanding the mechanistic basis of their actions.},
}
@article {pmid41007725,
year = {2025},
author = {Alfahaid, A and Morris, T and Cootes, T and Keane, PA and Khalid, H and Pontikos, N and Alharbi, F and Alalwany, E and Almars, AM and Aldweesh, A and ALMansour, AGM and Sergouniotis, PI and Balaskas, K},
title = {Machine Learning-Based Analysis of Optical Coherence Tomography Angiography Images for Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
pmid = {41007725},
issn = {2227-9059},
support = {MR/T019050/1//the UK Research and Innovation (UKRI) (MR/T019050/1 Future Leaders Fellowship to P.A.K.)/ ; NIHR203308//The research was also supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. It was also co-funded by the NIHR Manchester/ ; 224643/Z/21/Z//the Wellcome Trust (224643/Z/21/Z, Clinical Research Career Development Fellowship to P.I.S.)/ ; /WT_/Wellcome Trust/United Kingdom ; R190028A//This work was supported by the Moorfields Eye Charity (R190028A Career Development Award to P.A.K; R190031A Career Development Award to N.P.)/ ; },
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is the leading cause of visual impairment among the elderly. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that enables detailed visualisation of retinal vascular layers. However, clinical assessment of OCTA images is often challenging due to high data volume, pattern variability, and subtle abnormalities. This study aimed to develop automated algorithms to detect and quantify AMD in OCTA images, thereby reducing ophthalmologists' workload and enhancing diagnostic accuracy. Methods: Two texture-based algorithms were developed to classify OCTA images without relying on segmentation. The first algorithm used whole local texture features, while the second applied principal component analysis (PCA) to decorrelate and reduce texture features. Local texture descriptors, including rotation-invariant uniform local binary patterns (LBP2riu), local binary patterns (LBP), and binary robust independent elementary features (BRIEF), were combined with machine learning classifiers such as support vector machine (SVM) and K-nearest neighbour (KNN). OCTA datasets from Manchester Royal Eye Hospital and Moorfields Eye Hospital, covering healthy, dry AMD, and wet AMD eyes, were used for evaluation. Results: The first algorithm achieved a mean area under the receiver operating characteristic curve (AUC) of 1.00±0.00 for distinguishing healthy eyes from wet AMD. The second algorithm showed superior performance in differentiating dry AMD from wet AMD (AUC 0.85±0.02). Conclusions: The proposed algorithms demonstrate strong potential for rapid and accurate AMD diagnosis in OCTA workflows. By reducing manual image evaluation and associated variability, they may support improved clinical decision-making and patient care.},
}
@article {pmid41007616,
year = {2025},
author = {Kocab, AJ and Cano, M and Bacellar-Galdino, M and Jamison, JA and Brock, WJ and Zacks, DN and Handa, JT},
title = {In Vivo Characterization of ONL1204, a Small Peptide Inhibitor of the Fas Receptor, as a Potential Neuroprotective Therapy for Geographic Atrophy and Dry Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {13},
number = {9},
pages = {},
pmid = {41007616},
issn = {2227-9059},
support = {R42 EY029625/EY/NEI NIH HHS/United States ; 5R42EY029625-23/NH/NIH HHS/United States ; },
abstract = {Background: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the developed world, and the approved products for geographic atrophy (GA), a late-stage form of dry AMD, have shown limited efficacy and require frequent administration. Therefore, longer-lasting therapies with improved efficacy would be a welcome addition to AMD treatment. One potential therapeutic is ONL1204, a small peptide inhibitor of the Fas receptor that has prevented cell death and inflammation in retinal disease models. This study characterizes the pharmacokinetics (PK) and durability of protection conferred by ONL1204. Methods: Ocular pharmacokinetic profiles were generated over 3 months in rabbit and minipig following a single intravitreal (IVT) injection of ONL1204 at multiple doses. Ocular pharmacodynamics were evaluated in two models: a rabbit model using a single IVT injection of ONL1204 with a delayed sodium iodate challenge coupled with fluorescein angiography to quantify RPE loss, and a chronic mouse model that reflects key features of dry AMD disease pathology to assess the efficacy of repeat IVT administrations of ONL1204. Results: ONL1204 had prolonged residence in the ocular tissues of rabbit and minipig, with a vitreous humor half-life of over 100 days. ONL1204 demonstrated significant protection of the retinal pigment epithelium (RPE) in the rabbit sodium iodate model. In the chronic mouse model, two administrations of ONL1204 preserved RPE morphology, reduced caspase-8 activity, and decreased inflammation. Conclusions: These data represent key characteristics of ONL1204, highlighting its clinical potential as a therapeutic for chronic retinal diseases, including GA.},
}
@article {pmid41007159,
year = {2025},
author = {Liew, A and Agaian, S},
title = {Comprehensive Survey of OCT-Based Disorders Diagnosis: From Feature Extraction Methods to Robust Security Frameworks.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {9},
pages = {},
pmid = {41007159},
issn = {2306-5354},
abstract = {Optical coherence tomography (OCT) is a leading imaging technique for diagnosing retinal disorders such as age-related macular degeneration and diabetic retinopathy. Its ability to detect structural changes, especially in the optic nerve head, has made it vital for early diagnosis and monitoring. This paper surveys techniques for ocular disease prediction using OCT, focusing on both hand-crafted and deep learning-based feature extractors. While the field has seen rapid growth, a detailed comparative analysis of these methods has been lacking. We address this by reviewing research from the past 20 years, evaluating methods based on accuracy, sensitivity, specificity, and computational cost. Key diseases examined include glaucoma, diabetic retinopathy, cataracts, amblyopia, and macular degeneration. We also assess public OCT datasets widely used in model development. A unique contribution of this paper is the exploration of adversarial attacks targeting OCT-based diagnostic systems and the vulnerabilities of different feature extraction techniques. We propose a practical, robust defense strategy that integrates with existing models and outperforms current solutions. Our findings emphasize the value of combining classical and deep learning methods with strong defenses to enhance the security and reliability of OCT-based diagnostics, and we offer guidance for future research and clinical integration.},
}
@article {pmid41006661,
year = {2025},
author = {Most, JA and Folk, GA and Walker, EH and Nagel, ID and Mehta, NN and Flester, E and Borooah, S},
title = {Evaluating the clinical utility of multimodal large language models for detecting age-related macular degeneration from retinal imaging.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33214},
pmid = {41006661},
issn = {2045-2322},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/diagnosis ; Female ; Male ; Aged, 80 and over ; Retrospective Studies ; Aged ; *Retina/diagnostic imaging/pathology ; Severity of Illness Index ; Large Language Models ; },
abstract = {This single-center retrospective study evaluated the performance of four multimodal large language models (MLLMs) (ChatGPT-4o, Claude 3.5 Sonnet, Google Gemini 1.5 Pro, Perplexity Sonar Large) in detecting and grading the severity of age-related macular degeneration (AMD) from ultrawide field fundus images. Images from 76 patients (136 eyes; mean age 81.1 years; 69.7% female) seen at the University of California San Diego were graded independently for AMD severity by two junior retinal specialists (and an adjudicating senior retina specialist for disagreements) using the Age-Related Eye Disease Study (AREDS) classification. The cohort included 17 (12.5%) eyes with 'No AMD', 18 (13.2%) with 'Early AMD', 50 (36.8%) with 'Intermediate AMD', and 51 (37.5%) with 'Advanced AMD'. Between December 2024 and February 2025, each MLLM was prompted with single images and standardized queries to assess the primary outcomes of accuracy, sensitivity, and specificity in binary disease classification, disease severity grading, open-ended diagnosis, and multiple-choice diagnosis (with distractor diseases). Secondary outcomes included precision, F1 scores, Cohen's kappa, model performance comparisons, and error analysis. ChatGPT-4o demonstrated the highest accuracy for binary disease classification [mean 0.824 (95% confidence interval (CI)): 0.743, 0.875)], followed by Perplexity Sonar Large [mean 0.815 (95% CI: 0.744, 0.879)], both of which were significantly more accurate (P < 0.00033) Than Gemini 1.5 Pro [mean 0.669 (95% CI: 0.581, 0.743)] and Claude 3.5 Sonnet [mean 0.301 (95% CI: 0.221, 0.375)]. For severity grading, Perplexity Sonar Large was most accurate [mean 0.463 (95% CI: 0.368, 0.537)], though differences among models were not statistically significant. ChatGPT-4o led in open-ended and multiple-choice diagnostic tasks. In summary, while MLLMs show promise for automated AMD detection and grading from fundus images, their current reliability is insufficient for clinical application, highlighting the need for further model development and validation.},
}
@article {pmid41006570,
year = {2025},
author = {Terheyden, JH and Gittel, L and Wu, Z and Guymer, RH and Finger, RP},
title = {Associations between patient-reported vision impairment in low luminance and vision-related quality of life in intermediate age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33317},
pmid = {41006570},
issn = {2045-2322},
mesh = {Humans ; *Quality of Life ; Female ; Aged ; Male ; *Macular Degeneration/physiopathology/psychology ; Cross-Sectional Studies ; Aged, 80 and over ; Surveys and Questionnaires ; Visual Acuity ; *Vision Disorders/physiopathology ; Middle Aged ; Vision, Ocular ; },
abstract = {Intermediate age-related macular degeneration (iAMD) reduces vision under low-luminance conditions, affecting quality of life (QoL). The Vision Impairment in Low Luminance (VILL) questionnaire captures QoL domains relevant in iAMD but most AMD studies use the generic vision-related QoL measure Visual Function Questionnaire (NEI VFQ). To investigate associations between these generic and specific vision-related QoL instruments, and explore the added value of including the VILL over the NEI VFQ in future iAMD studies, we analysed cross-sectional study data from individuals with iAMD. Associations were investigated using age-adjusted regression models. We included 150 participants (73% women, 74.6 ± 7.8 years). VILL subscale scores were associated with NEI VFQ scores (p ≤ 0.014) and explained 62.0% to 67.9% in the variance of the NEI VFQ scores. Ceiling effects were more common in the visual functioning NEI VFQ subscale than in the VILL-Reading subscale (p = 0.039), while the emotional well-being scores did not differ signficiantly between the instruments. NEI VFQ scores, VILL-Reading and VILL-Mobility subscale scores were associated with best-corrected visual acuity in either eye. Thus, assessments of vision-related QoL in iAMD using a generic instrument and a low luminance vision-specific instrument yield comparable but not identical results. The VILL has less ceiling effects than the NEI VFQ, suggesting its suitability for iAMD intervention trials and added value over the NEI VFQ in populations with few functional deficits.},
}
@article {pmid41006457,
year = {2025},
author = {Masaoka, M and Yamashiro, K},
title = {Switching to faricimab from aflibercept during maintenance treatment period for age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33100},
pmid = {41006457},
issn = {2045-2322},
mesh = {Humans ; Female ; Male ; Aged ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Visual Acuity/drug effects ; *Macular Degeneration/drug therapy ; Aged, 80 and over ; Treatment Outcome ; Drug Substitution ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {To compare the short-term treatment outcomes of aflibercept and faricimab for neovascular age-related macular degeneration (nAMD) during the maintenance treatment period, we included 82 eyes of 74 patients who switched from aflibercept to faricimab between July 2022 and July 2023, when approximately 80% of the patients with nAMD received faricimab treatment. Visual acuity and retinal exudative changes in the macular and subfoveal areas were evaluated over three months following a single injection of either aflibercept or faricimab. Faricimab resulted in a longer period of significant reduction in retinal exudative changes than aflibercept, whereas visual acuity remained stable with either treatment. Visual acuity analysis, divided by nAMD subtype and the presence of pachychoroid, indicated no clinically significant differences between aflibercept and faricimab. However, faricimab showed stronger fluid suppression in patients with nAMD without pachychoroid, with significant suppression of macular and subfoveal fluids, especially in the intraretinal fluid. These findings suggest that faricimab may be more effective than aflibercept in controlling retinal exudative changes in nAMD during maintenance treatment, particularly in patients without pachychoroid.},
}
@article {pmid41006433,
year = {2025},
author = {Bradley, A and Park, S and Park, S and Kim, K and Galdamez, A and Min, H and Diaz-Aguilar, MS and Hartnett, ME and Lee, EJ and Lin, JH},
title = {Targeting ATF6 reduces pathological neovascularization and improves visual outcomes in retinal disease models.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33070},
pmid = {41006433},
issn = {2045-2322},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; Merit I01BX002284//U.S. Department of Veterans Affairs/ ; DISC2-10973//California Institute for Regenerative Medicine/ ; P30EY026877/NH/NIH HHS/United States ; I01 BX002284/BX/BLRD VA/United States ; },
mesh = {Animals ; *Activating Transcription Factor 6/metabolism/genetics/antagonists &amp; inhibitors ; Mice ; *Retinal Neovascularization/metabolism/pathology/genetics ; Disease Models, Animal ; Unfolded Protein Response/genetics ; Mice, Knockout ; Signal Transduction ; Retinopathy of Prematurity/metabolism/pathology ; Retina/metabolism/pathology ; Mice, Inbred C57BL ; Cell Proliferation ; },
abstract = {Pathological retinal neovascularization is a cause of vision loss in diseases including retinopathy of prematurity (ROP), wet age-related macular degeneration (AMD), and diabetic retinopathy. The Unfolded Protein Response (UPR) is an intracellular signal transduction mechanism that is activated by ER stress and upregulates many proteins, including angiogenesis factors like VEGF and HIF-1α. This suggests that UPR genes and pathways may drive retinal angiogenesis. Here, we tested the role of the UPR regulator Activating Transcription Factor 6 (ATF6) in pathological and developmental retinal angiogenesis. We induced pathological retinal neovascularization in Atf6[-/-] mice using the oxygen-induced retinopathy (OIR) model and found significantly preserved visual function, accompanied by decreased retinal neovascularization, endothelial cell proliferation, and UPR transcriptional program induction. When we chemically blocked ATF6 signaling by intraocular injection of the small molecule Ceapin-A7, we also saw suppressed retinal expression of UPR genes. Additionally, in postnatal day 7 Atf6[-/-] mice when the retinal vasculature is developing in response to physiologic intraocular hypoxia, there was a transient but significant defect in pruning and retinal blood vessel extension. Together, our results demonstrate ATF6's causal role in developmental and pathological retinal angiogenesis and highlight its potential as a therapeutic target to preserve vision in retinal neovascularization diseases.},
}
@article {pmid41005881,
year = {2026},
author = {Wang, J and Gao, Y and Lin, Y and Wu, IXY and Xiao, F},
title = {Residential greenness, air pollution, and incident age-related macular degeneration: A prospective cohort study.},
journal = {Journal of environmental sciences (China)},
volume = {159},
number = {},
pages = {242-249},
doi = {10.1016/j.jes.2025.04.014},
pmid = {41005881},
issn = {1001-0742},
mesh = {*Air Pollution/statistics &amp; numerical data ; *Macular Degeneration/epidemiology ; Humans ; Prospective Studies ; *Air Pollutants/analysis ; *Environmental Exposure/statistics &amp; numerical data ; Particulate Matter/analysis ; China/epidemiology ; Aged ; Male ; Female ; Nitrogen Oxides/analysis ; Incidence ; Middle Aged ; },
abstract = {Existing evidence suggests residential greenness is beneficial to human, while no research to date explored the associations of greenness with age-related macular degeneration (AMD). To evaluate the association of greenness with AMD, modification and mediation effect of air pollution, we conducted this prospective study. We constructed weighted quantile sum (WQS) index as co-exposure to nitrogen oxides (NOx), particulate matter <2.5 µm (PM2.5), particulate matter <10 µm (PM10). Stratified Cox regression models were applied to test the effect of exposure. Effect modification of air pollution was assessed. Stratified Cox models through the indirect method and Aalen additive risk models were used in mediation analysis. Over median follow-up of 11.67 years, 4596 AMD events were ascertained. Hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) of incident AMD for pollution per interquartile range (IQR) increment were 1.10 (1.04-1.16) for nitrogen dioxide (NO2), 1.09 (1.03-1.15) for NOx, 1.14 (1.05-1.24) for PM2.5, 1.13 (1.05-1.21) for PM10. The HR (95 % CI) of AMD associated with greenness 1000 m buffer per IQR increment was 0.91 (0.86-0.97), 300 m buffer was 0.94 (0.89-0.99). The association between greenness 1000 m and AMD was 28.59 %, 44.77 %, 35.59 %, 32.31 % and 27.08 % mediated by the decreased WQS index, NO2, NOx, PM2.5 and PM10, respectively. Increased greenness was associated with lower AMD incidence, and air pollution partly mediate it, which implies that interventions aimed at improving air quality and increasing greenness could have a dual benefit in mitigating AMD risk.},
}
@article {pmid41005608,
year = {2025},
author = {Suzuki, T and Nagahara, M and Hayashi, K and Shiraya, T and Terao, R and Honjo, M and Ueta, T},
title = {NaIO3-induced RPE toxicity leads to chorioretinal atrophy, scleral remodeling, and myopic axial elongation in mice.},
journal = {Experimental eye research},
volume = {261},
number = {},
pages = {110665},
doi = {10.1016/j.exer.2025.110665},
pmid = {41005608},
issn = {1096-0007},
mesh = {Animals ; *Retinal Pigment Epithelium/drug effects/pathology ; Mice ; *Iodates/toxicity ; *Sclera/pathology/drug effects ; Disease Models, Animal ; Mice, Inbred C57BL ; *Axial Length, Eye/pathology ; *Choroid/pathology/drug effects ; Atrophy ; *Myopia, Degenerative/chemically induced/pathology/metabolism ; Male ; Tomography, Optical Coherence ; },
abstract = {Pathologic myopia, a vision-threatening subtype of myopia, is characterized by axial elongation accompanied by chorioretinal atrophy and scleral remodeling. While lens-induced and form-deprivation myopia models have elucidated the role of visual input in ocular growth, the contribution of retinal pigment epithelium (RPE) and choriocapillaris (CC) damages remains incompletely understood. Here, we employed a sodium iodate (NaIO3) model-traditionally used in age-related macular degeneration research-to investigate whether the damage to the RPE and CC can induce changes in the sclera and axial length. We demonstrate that systemic NaIO3 exposure induced widespread RPE and CC degeneration, retinal thinning, and chorioretinal atrophy, all of which were partially rescued by the ferroptosis inhibitor ferrostatin-1 (Fer-1) in mice. These degenerative changes correlated with a significant myopic shift (∼15 D) and axial elongation (∼0.3 mm), alongside scleral thinning, decreased COL1A1 expression, and reduced collagen fibril diameter-hallmarks of scleral extracellular matrix remodeling. Fer-1 treatment attenuated both the anatomical and molecular features of myopia, supporting a causal role of lipid peroxidation in this process. Our findings demonstrate that lipid peroxidation-associated RPE and CC damage can trigger scleral remodeling and axial elongation independent of visual input, providing a novel mechanistic insight into ocular growth regulation. The NaIO3 model may therefore serve as a unique and reproducible platform for studying chorioretinal degeneration-driven myopia and evaluating lipid peroxidation-targeting therapies.},
}
@article {pmid41003471,
year = {2025},
author = {Kasi, A and Tan, J and Rosen, R and Deobhakta, A and Dhamoon, M and Lema, G and Bhuiyan, A and Yannuzzi, L and Smith, RT},
title = {Re: Chen et al.: High-density lipoproteins associated with age-related macular degeneration in the All of Us research program (Ophthalmology. 2025;132:684-691).},
journal = {Ophthalmology},
volume = {132},
number = {12},
pages = {e194-e195},
doi = {10.1016/j.ophtha.2025.08.017},
pmid = {41003471},
issn = {1549-4713},
}
@article {pmid41002181,
year = {2025},
author = {Zhang, M and Mo, Y and Gao, J and Qu, W and Chen, A and Wu, S and Zhang, Y},
title = {Complement and local ocular inflammatory response: Chronic immune factors in myopia.},
journal = {Science progress},
volume = {108},
number = {3},
pages = {368504251383046},
pmid = {41002181},
issn = {2047-7163},
mesh = {Humans ; *Myopia/immunology/pathology ; *Complement System Proteins/immunology/metabolism ; *Inflammation/immunology/pathology ; Complement Activation/immunology ; Animals ; Immunity, Innate ; },
abstract = {Myopia has emerged as a globally pervasive visual disorder, with its incidence rising steadily, particularly among children and adolescents, posing a significant threat to ocular health. Recent research underscores a strong link between chronic inflammatory processes and both the onset and progression of myopia. As a cornerstone of the innate immune system, the complement cascade plays a pivotal role in mediating ocular inflammatory diseases associated with high myopia, including macular degeneration, glaucoma, allergic conjunctivitis, uveitis, and scleritis. Accumulating evidence indicates that complement activation contributes to myopia pathogenesis by orchestrating local inflammatory responses within the eye. This article is a narrative review that synthesizes current evidence on complement-myopia interactions, with a focus on the underlying biological mechanisms and their potential as therapeutic targets for both preventing and managing myopia.},
}
@article {pmid41002105,
year = {2025},
author = {Schloesser, L and Terheyden, JH and Behning, C and Klinkhammer, H and Garzone, D and Saßmannshausen, M and Thiele, S and Schmitz-Valckenberg, S and Hoyng, C and Sánchez, CI and Schmid, M and Luhmann, UFO and Floyd, H and Leal, S and Holz, FG and Finger, RP and , },
title = {Associations Between Structural Phenotype and Polygenic Risk Scores in Intermediate Age-Related Macular Degeneration - A MACUSTAR Report.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {9},
pages = {37},
pmid = {41002105},
issn = {2164-2591},
mesh = {Humans ; Female ; Aged ; Male ; *Macular Degeneration/genetics/pathology ; Phenotype ; Prospective Studies ; *Multifactorial Inheritance ; Middle Aged ; Risk Factors ; Aged, 80 and over ; Biomarkers ; Genetic Predisposition to Disease ; Retinal Pigment Epithelium/pathology ; Genetic Risk Score ; Proteins ; },
abstract = {PURPOSE: The purpose of this study was to analyze genotype-phenotype associations in intermediate age-related macular degeneration (iAMD) based on global and pathway-specific polygenic risk scores (psPRS) in participants of the prospective European multicenter cohort study MACUSTAR.<br><br>METHODS: Assessed structural biomarkers included reticular pseudodrusen (RPD), pigmentary abnormalities, hyper-reflective foci (HRF), and incomplete or complete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA and cRORA). Blood samples were genotyped and imputed via a local pipeline. Global and pathway-specific PRS (complement PRS [C-PRS], with and without ARMS2/HTRA1 variants [C+AH-PRS and AH-PRS]; extracellular matrix PRS [E-PRS]; and lipid PRS [L-PRS]) were calculated. The associations between global and pathway-specific PRS and structural iAMD biomarkers were assessed with multivariable models, controlling for age and sex.<br><br>RESULTS: In total, 404 participants (263 women, 65.1%; mean age = 71.5 &#xb1; 7.0 years, mean &#xb1; standard deviation [SD]) were included in the analysis. Multivariable regression models revealed that RPD was associated with a higher AH-PRS (estimate = 7.11 &#xd7; 10-2, P = 9.0 &#xd7; 10-3), C+AH-PRS (estimate = 9.96 &#xd7; 10-2, P = 5.0 &#xd7; 10-3), and E-PRS (estimate = 3.28 &#xd7; 10-2, P = 3.1 &#xd7; 10-2). The presence of cRORA was associated with a higher AH-PRS (estimate = 1.34 &#xd7; 10-1, P = 2 &#xd7; 10-3) and a higher C+AH-PRS (estimate = 1.59 &#xd7; 10-1, P = 6 &#xd7; 10-3).<br><br>CONCLUSIONS: Structural risk biomarkers are associated with psPRS in iAMD. These findings further underscore the heterogeneity of pathogenic pathways in AMD and indicate differential risk characteristics across the broad spectrum of iAMD.<br><br>TRANSLATIONAL RELEVANCE: Our findings reveal subgroups in iAMD based on genotype-phenotype associations which can help identifying patients at high risk for iAMD and establish new endpoints for clinical trials in iAMD.},
}
@article {pmid41000856,
year = {2025},
author = {Maddipatla, R and Bartuzel, MM and Pijewska, E and Langlo, CS and Zawadzki, RJ and Jonnal, RS},
title = {Subretinal aspects of the optoretinographic response.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41000856},
issn = {2692-8205},
support = {R01 EY026556/EY/NEI NIH HHS/United States ; R01 EY031098/EY/NEI NIH HHS/United States ; P30 EY012576/EY/NEI NIH HHS/United States ; R01 EY034340/EY/NEI NIH HHS/United States ; R01 EY033532/EY/NEI NIH HHS/United States ; },
abstract = {Water movement in the living human retina and its regulation are important components of the tissue's structural integrity, optical properties, and homeostasis. In the outer retina there is a continuous flow of water from the subretinal space, through the retinal pigmented epithelium, and into the choroid. This flow is disrupted acutely in disorders such as retinal detachment and central serous retinopathy, and is also known to reduce dramatically with age and age-related macular degeneration. Optoretiongraphy is an emerging technique for measuring neural function in the retina by monitoring nanometer-scale deformations of the membranes of photoreceptors. These deformations have been hypothetically attributed, in part, to osmotic shifts that cause water to move into and out of the photoreceptor outer segment after light stimulation. In the present work, we describe a method for measuring changes in the lengths of the cone outer segment and subretinal space in parallel and results showing that light stimuli change the volume of the subretinal space. These results are consistent with earlier ex vivo measurements of its light-induced hydration. The magnitude of the latter changes depend on the rate of water clearance from the subretinal space, and thus may serve as an indicator of the health of the water transport system. In addition, they may help us understand the mechanisms underlying the photoreceptor optoretinogram. These findings add to a growing understanding of the ways in which light exposure leads to transient reconfigurations of the outer retinal layers lasting milliseconds to hours.},
}
@article {pmid41000371,
year = {2025},
author = {Wu, T and Esfandiari, M and Zhang, P and Taylor, RH and Gehlbach, P and Iordachita, I},
title = {Deep Learning-Enhanced Robotic Subretinal Injection with Real-Time Retinal Motion Compensation.},
journal = {IEEE International Conference on Automation Science and Engineering (CASE) : [proceedings]. IEEE Conference on Automation Science and Engineering},
volume = {2025},
number = {},
pages = {1285-1291},
pmid = {41000371},
issn = {2161-8070},
support = {R01 EB023943/EB/NIBIB NIH HHS/United States ; R01 EB025883/EB/NIBIB NIH HHS/United States ; R01 EB034397/EB/NIBIB NIH HHS/United States ; },
abstract = {Subretinal injection is a critical procedure for delivering therapeutic agents to treat retinal diseases such as inherited retinal diseases (IRD) and age-related macular degeneration (AMD). However, retinal motion caused by physiological factors such as respiration and heartbeat significantly impacts precise needle positioning, increasing the risk of retinal pigment epithelium (RPE) damage. This paper presents a fully autonomous robotic subretinal injection system that integrates intraoperative optical coherence tomography (iOCT) imaging and deep learning-based motion prediction to synchronize needle and retinal motion. A Long Short-Term Memory (LSTM) neural network is used to predict internal limiting membrane (ILM) motion, outperforming a Fast Fourier Transform (FFT)-based baseline model. Additionally, a real-time registration framework aligns the needle tip position with the robot's coordinate frame. Then, a dynamic proportional speed control strategy ensures smooth and adaptive needle insertion. Experimental validation in both simulation and ex vivo open-sky porcine eyes demonstrates precise motion synchronization and successful subretinal injections. The experiments achieve a mean tracking error below 16.4 μm in pre-insertion phases. These results show the potential of AI-driven robotic assistance to improve the safety and accuracy of retinal microsurgery.},
}
@article {pmid41000209,
year = {2025},
author = {Cheong, KX and Jiang, Y and Htoon, HM and Pan, W and Foo, LL and Hu, Z and Chen, L and Ang, S and Lamoureux, EL and Hoang, QV and Saw, SM and Lan, W},
title = {Characteristics of Myopic Traction Maculopathy in the Aier-SERI High Myopia Adult Cohort Study.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100894},
pmid = {41000209},
issn = {2666-9145},
abstract = {PURPOSE: To describe the prevalence, clinical characteristics, associations, and visual outcomes of myopic traction maculopathy (MTM), which was defined by the presence of retinoschisis (RS), macular holes (MHs), or foveal retinal detachment (RD), in an adult high myope cohort in Changsha, China.<br><br>DESIGN: A cross-sectional study.<br><br>PARTICIPANTS: Chinese adults with high myopia (defined as spherical equivalent [SE] less than or equal to -5 diopters [D]) in the Aier-Singapore Eye Research Institute High Myopia Adult Cohort Study, which is a prospective population-based study.<br><br>METHODS: Swept-source OCT was performed to detect RS, MH, and foveal RD. Multivariable generalized estimating equation analyses were performed to assess associations of MTM and the impact of MTM on best-corrected visual acuity (BCVA).<br><br>MAIN OUTCOME MEASURES: Prevalence, clinical characteristics, associations, and visual outcomes of MTM.<br><br>RESULTS: Of 437 participants (839 eyes), MTM was observed in 20 participants with a prevalence of 4.6% (by participants) or in 24 eyes (with a prevalence of 2.9%; by eyes). Overall, the whole cohort (64.7% female) had a mean age of 42.9 &#xb1; 7.2 years, an SE of -9.5 &#xb1; 4.4 D, and an axial length (AL) of 27.3 &#xb1; 1.9 mm. Retinoschisis was the most common lesion (91.7%; 22/24 eyes with MTM). In the multivariable analysis, the prevalence of MTM was associated with a more myopic SE (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.01-1.18; P = 0.03), longer AL (OR: 1.30; 95% CI: 1.03-1.65; P = 0.03), myopic macular degeneration (MMD) (OR: 12.77; 95% CI: 3.18-51.24; P < 0.001), and older age (OR: 1.06; 95% CI: 1.01-1.11; P = 0.01). In the multivariable analysis, the prevalence of MTM was also associated with poorer BCVA (beta coefficient: -0.07; 95% CI: -0.13 to -0.01; P < 0.01).<br><br>CONCLUSIONS: The prevalence of MTM was 4.6% in an adult high myope cohort. Associations with MTM include more myopic SE, longer AL, MMD, and older age. Myopic traction maculopathy is associated with poorer vision.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid40999227,
year = {2025},
author = {Borrelli, E and Boscia, F and Lanzetta, P and Lupidi, M and Mastropasqua, R and Nicolò, M and Parravano, M and Ricci, F and Staurenghi, G and Vadalà, M and Viola, F and Vujosevic, S and Bandello, F},
title = {Intravitreal faricimab for diabetic macular oedema and neovascular age-related macular degeneration: general considerations and practical recommendations by an expert panel of Italian retina specialists.},
journal = {Eye (London, England)},
volume = {39},
number = {16},
pages = {3005-3014},
pmid = {40999227},
issn = {1476-5454},
mesh = {Humans ; Intravitreal Injections ; *Macular Edema/drug therapy/etiology/diagnosis ; *Diabetic Retinopathy/drug therapy ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Italy ; *Wet Macular Degeneration/drug therapy/diagnosis ; Consensus ; Visual Acuity ; Antibodies, Bispecific ; },
abstract = {BACKGROUND/OBJECTIVES: Faricimab, a bispecific antibody targeting angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A), introduces a novel therapeutic option for diabetic macular oedema (DMO) and neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This consensus document, developed by an expert panel of Italian retina specialists, provides practical recommendations for the integration of faricimab into clinical practice.<br><br>RESULTS: The panel reviewed pivotal clinical trials, YOSEMITE and RHINE for DMO and TENAYA and LUCERNE for nAMD, which demonstrated faricimab's noninferiority to aflibercept in vision outcomes while offering extended dosing intervals up to 16 weeks. Key benefits include rapid and sustained fluid resolution, enhanced macular dryness, and reduced treatment burden for patients and healthcare systems. Recommendations cover treatment initiation, tailored management using treat-and-extend protocols, and strategies for switching from other anti-VEGF therapies.<br><br>CONCLUSION: The consensus highlights faricimab's potential to optimise outcomes for patients with DMO and nAMD while addressing real-world challenges, such as undertreatment and clinic resource constraints.},
}
@article {pmid40999046,
year = {2025},
author = {Lorenz, AT and Messias, AM and Darwisch, W and Roberts, PK and Boden, KT and Szurman, P and Stanzel, BV},
title = {AI-based fluid quantification in neovascular age-related macular degeneration and diabetic macular edema treated with faricimab - a real-life study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {40999046},
issn = {1435-702X},
support = {SL45295//Roche Deutschland/ ; },
abstract = {PURPOSE: To assess faricimab treatment in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) with artificial intelligence-based fluid quantification on spectral-domain optical coherence tomography (SD-OCT).<br><br>METHODS: Retrospective patients with nAMD and DME; treatment-na&#xef;ve, or on another intravitreal medication (switchers), loaded with 4 monthly intravitreal faricimab. SD-OCT (Heidelberg Engineering) at baseline and 16&#xa0;weeks, then processed using the Fluid Monitor&#xae; (RetInSight). Sum of fluid volumes in the central 1&#xa0;mm (pigment epithelial detachment, subretinal fluid, and intraretinal fluid) was computed (SF) and correlated with central subfield thickness (CST).<br><br>RESULTS: Thirty-four nAMD (25 switchers) and 21 DME (20 switchers) eyes were included. SF (nL) was 126.68&#x2009;&#xb1;&#x2009;17.24 and 37.84&#x2009;&#xb1;&#x2009;8.31 at baseline reduced to 80.78&#x2009;&#xb1;&#x2009;15.56 (p&#x2009;<&#x2009;0.0001) and 15.28&#x2009;&#xb1;&#x2009;4.94 (p&#x2009;<&#x2009;0.0001) for nAMD and DME, respectively. CST (&#xb5;m) reduced from 405.12&#x2009;&#xb1;&#x2009;24.95 and 354.97&#x2009;&#xb1;&#x2009;15.89 to 320.33&#x2009;&#xb1;&#x2009;19.80 (p&#x2009;=&#x2009;0.0001) and 302.41&#x2009;&#xb1;&#x2009;11.55 (p&#x2009;<&#x2009;0.0001) in nAMD and DME, respectively. Mean intraindividual change between baseline and 16&#xa0;weeks was larger using SF than with CST for nAMD (36.5% and 17.6%, respectively) and for DME (56.2% and 13.1%, respectively). A similar pattern was observed for each retinal compartment.<br><br>CONCLUSION: When loaded with faricimab, total fluid decreased by 37% in nAMD and 56% in DME. Fluid volumetry appears more sensitive for retinal fluid.<br><br>TRANSLATIONAL RELEVANCE: When AI-fluid volumetry is applied real-world nAMD and DME cases, then fluid volume offers a more sensitive and quantifiable measure of disease activity than CST.},
}
@article {pmid40998972,
year = {2025},
author = {Fuchs, P and Schmidt-Erfurth, U and Coulibaly, LM and Bogunovic, H and Leingang, O and Gruber, A and Frommlet, F and Mares, V and Barthelmes, D and Reiter, GS},
title = {Impact of AI-quantified fluid dynamics on visual outcomes over 5 years in patients with treatment-naïve nAMD from the FRB! registry.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {32881},
pmid = {40998972},
issn = {2045-2322},
mesh = {Humans ; Female ; Male ; Aged ; Registries ; *Visual Acuity ; Tomography, Optical Coherence ; Aged, 80 and over ; Middle Aged ; *Artificial Intelligence ; *Subretinal Fluid ; *Macular Degeneration/physiopathology ; Algorithms ; Hydrodynamics ; Treatment Outcome ; },
abstract = {To investigate the impact of retinal fluid dynamics on visual outcomes in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) treated in the real world over 5 years using approved AI-based fluid monitoring. Real-world data comprising OCT scans and electronic medical records from 148 patients (187 eyes) were extracted from the Fight Retinal Blindness! (FRB!) Zürich database. OCT scans were analysed using an approved AI algorithm (RetInSight, Vienna, Austria) to quantify fluid volumes by compartements. The impact of fluid persistence and fluctuations on BCVA change was assessed using forward stepwise regression and mixed models. Fluid compartments were further categorized into quartiles (SD-Qs), and the effect of fluid fluctuations on BCVA analysed (SD-Q1 least and SD-Q4 greatest variability of fluctuations). The greatest PED fluctuations in the central 1-mm showed an accentuated BCVA decrease after 2 and 4 years (estimate: -0.07, P = 0.019; estimate: -0.15, P < 0.01). After 4 years, eyes in SD-Q4 compared with SD-Q1 with greater PED fluctuations in the central 1-mm and 6-mm area were affected by a significant mean reduction in BCVA (-5.7 letters (P = 0.013); -6.1 letters (P = 0.015)). Greater intraretinal fluid (IRF) fluctuations (central 1-mm) (SD-Q4 compared with SD-Q1) were associated with a significantly worse mean BCVA by -6.8 letters (P = 0.018) after 5 years. Fluid persistence was not associated with statistically significant BCVA changes. In routine clinical management of nAMD, greater fluctuations of PED and IRF correlate with worse BCVA outcomes over long-term follow-up. A well-suited treatment regimen is required in the real world which can be utilized with AI-based fluid monitoring.},
}
@article {pmid40998549,
year = {2025},
author = {Yanai, R and Murao, F and Miki, A and Terasaki, H and Chujo, S and Sakaeda, Y and Seki, K and Ishigouoka, G and Iwase, T and Ohara, H and Tsujinaka, H and Fukuyama, H and Abe, Y and Nishi, Y and Kinoshita, T and Kondo, M and Sakamoto, T and Mitamura, Y and , },
title = {6-month outcomes of intravitreal faricimab injection for neovascular age-related macular degeneration and their relationships with clinical findings: a multicentre cohort study from the J-CREST.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40998549},
issn = {2397-3269},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; *Visual Acuity ; Female ; Male ; Aged ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Time Factors ; Macula Lutea/pathology ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {BACKGROUND/AIMS: This study aimed to investigate the outcomes of intravitreal faricimab (IVF) injection for neovascular age-related macular degeneration (nAMD) and their relationships with clinical findings.<br><br>METHODS: At 14 sites, we retrospectively examined the 6-month treatment outcomes of 186 eyes that underwent IVF for treatment-na&#xef;ve nAMD or nAMD previously treated except for >3 months before the baseline.<br><br>RESULTS: Visual acuity and central retinal thickness (CRT) significantly improved at 1, 3 and 6 months after treatment (p<0.001, respectively). At 3 or 6 months, 151 eyes (81.2%) exhibited dry macula. The dry macula rate in the treatment-na&#xef;ve group (85.7%) was significantly higher than the previously treated group (71.7%, p=0.022). Eyes with pretreatment submacular haemorrhage (SMH) had a significantly higher rate of dry macula (93.9%) than those without (78.4%, p=0.048). Eyes with pretreatment subretinal fluid had good final visual acuity, but poor visual acuity was observed in those with intraretinal fluid (IRF), subretinal hyper-reflective material (SHRM), SMH or hard exudates. However, a similar tendency was also observed at baseline. CRT improvement was good in the eyes with pretreatment IRF, pigment epithelial detachment, SHRM and SMH, although these eyes had higher CRT at the baseline.<br><br>CONCLUSION: IVF treatment for nAMD was associated with improvements in visual acuity and CRT over 6 months. Eyes presenting with SMH showed a higher rate of achieving a dry macula. This result indicates that faricimab may be useful in treating patients with nAMD and SMH. Given the retrospective, non-randomised design, however, these findings should be interpreted cautiously and viewed as hypothesis-generating rather than definitive.},
}
@article {pmid40997603,
year = {2025},
author = {Yin, Y and Zhao, T},
title = {CircRNA MALAT1/miR-96-5p/FOXK2 axis regulates choroidal neovascularization.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100759},
pmid = {40997603},
issn = {1980-5322},
abstract = {OBJECTIVE: This study determined the role of circRNA MALAT1 (circ-MALAT1) in Choroidal Neovascularization (CNV).<br><br>METHODS: CNV mice were induced by laser photocoagulation, and Hypoxic human Retinal Microvascular Endothelial Cells (HRMECs) were induced using cobalt chloride. circ-MALAT1 expression pattern was determined in CNV mice and hypoxic HRMECs. Hematoxylin-eosin staining and fluorescein fundus angiography were performed to examine focal areas in CNV mice. Endothelial cell proliferation and migration assay, tubule formation assay, and apoptosis assay were conducted to determine angiogenesis in vitro. Circ-MALAT1-mediated CNV development was investigated using bioinformatics, luciferase analysis, and RNA immunoprecipitation.<br><br>RESULTS: circ-MALAT1 expression was upregulated in laser-induced CNV mice and hypoxic HRMECs. circ-MALAT1 silencing delayed structural disorganization of choroidal membranes and the formation of CNV, which was abolished by miR-96-5p inhibitors. circ-MALAT1 silencing decreased HRMEC viability, proliferation, migration, and tube formation and promoted apoptosis. circ-MALAT1 acted as a miR-96-5p sponge, chelating and inhibiting miR-96-5p activity, which led to increased expression of FOXK2. miR-96-5p overexpression mimicked the anti-angiogenic effects mediated by circ-MALAT1 silencing. FOXK2 overexpression diminished circ-MALAT1 silencing-mediated inhibition of endothelial cell progression. Furthermore, significant upregulation of circ-MALAT1 and FOXK2 expression was detected in clinical samples from neovascular age-related macular degeneration patients.<br><br>CONCLUSION: The introduction of circ-MALAT1/miR-96-5p/FOXK2 as a potential therapeutic target in this study provides new insights into the molecular pathogenesis of CNV, but our preliminary study only hints at the possibility of this axis as a target for CNV intervention, and its clinical significance still needs to be validated with larger sample sizes.},
}
@article {pmid40997007,
year = {2025},
author = {Zang, P and Wang, C and Hormel, TT and Bailey, ST and Hwang, TS and Jia, Y},
title = {Clinically Explainable Disease Diagnosis based on Biomarker Activation Map.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2025.3614518},
pmid = {40997007},
issn = {1558-2531},
abstract = {OBJECTIVE: Artificial intelligence (AI)-based disease classifiers have achieved specialist-level performances in several diagnostic tasks. However, real-world adoption of these classifiers remains challenging due to the black box issue. Here, we report a novel biomarker activation map (BAM) generation framework that can provide clinically meaningful explainability to current AI-based disease classifiers.<br><br>METHODS: We designed the framework based on the concept of residual counterfactual explanation by generating counterfactual outputs that could reverse the decision-making of the disease classifier. The BAM was generated as the difference map between the counterfactual output and original input with postprocessing. We evaluated the BAM on four different disease classifiers, including an age-related macular degeneration classier based on fundus photography, a diabetic retinopathy classifier based on optical coherence tomography angiography, a brain tumor classifier based on magnetic resonance imaging (MRI), and a breast cancer classifier based on computerized tomography (CT) scans.<br><br>RESULTS: The highlighted regions in the BAM correlated highly with manually demarcated biomarkers of each disease.<br><br>CONCLUSION/SIGNIFICANCE: The BAM can improve the clinical applicability of an AI-based disease classifier by providing intuitive output clinicians can use to understand and verify the diagnostic decision.},
}
@article {pmid40996723,
year = {2025},
author = {Dail, R and Bertolucci, G and Thinda, S},
title = {Occlusive Retinal Vessels Associated With Intravitreal Aflibercept, 8.0 mg.},
journal = {JAMA ophthalmology},
volume = {143},
number = {11},
pages = {978-980},
doi = {10.1001/jamaophthalmol.2025.3027},
pmid = {40996723},
issn = {2168-6173},
}
@article {pmid40996501,
year = {2025},
author = {Verma, A and Nittala, MG and Haines, JL and Pericak-Vance, MA and Stambolian, D and Sadda, SR},
title = {Spatial distribution of Intra-retinal Hyper-reflective foci and impact on progression in eyes with intermediate Age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {40996501},
issn = {1435-702X},
support = {R01EY023164 and 1R01EY030614/EY/NEI NIH HHS/United States ; },
abstract = {AIM: To analyze the longitudinal spatial distribution characteristics of intraretinal hyperreflective foci (IHRF) in eyes with intermediate age-related macular degeneration (iAMD).<br><br>METHODS: The optical coherence tomography (OCT) data was collected from the Amish Eye Study, for all patients with evidence of iAMD and IHRF at baseline, who completed a 24 month (M24) follow up visit. Early Treatment Diabetic Retinopathy Study (ETDRS) rings were placed on the enface scans from all volume scans showing IHRF, and the frequency and the density of IHRF was measured in the central subfield (CSF; 1&#xa0;mm circle), the 1-3&#xa0;mm ring (parafoveal region) and the 3-6&#xa0;mm ring (perifoveal region). The distance of all IHRF lesions from the foveal center was measured.<br><br>RESULTS: Forty-nine eyes (40 subjects) had iAMD and IHRF at baseline and M24. 23 eyes (46.9%) showed progression to late AMD. The frequency of IHRF was greatest in the parafoveal ring, although the density was highest in the CSF. IHRF number and density numerically increased in all regions at M24, though the increase was significant only in the perifoveal region. Although regression analysis did not show a relationship between baseline IHRF distribution and risk for progression to late AMD at 2 years, eyes that developed late AMD at M24 tended to show a more eccentric distribution of IHRF over time.<br><br>CONCLUSIONS: IHRF do not distribute evenly across the macula in eyes with iAMD, with a higher density centrally, but greater frequency parafoveally. IHRF tend to distribute more peripherally over time, however, among eyes that progress to late AMD. These observations may provide new insights into the pathophysiology of these lesions.},
}
@article {pmid40995793,
year = {2025},
author = {Gillies, M},
title = {The Long Journey of Treatment for Wet Macular Degeneration, Is It Worth It?.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {7},
pages = {744-745},
doi = {10.1111/ceo.70004},
pmid = {40995793},
issn = {1442-9071},
}
@article {pmid40995309,
year = {2025},
author = {Hormel, TT and Jia, Y},
title = {Advancing optical coherence tomography angiography to the clinic.},
journal = {Taiwan journal of ophthalmology},
volume = {15},
number = {3},
pages = {333-343},
pmid = {40995309},
issn = {2211-5072},
abstract = {Optical coherence tomography (OCT) angiography (OCTA) is a new clinical technology that advances the capabilities of OCT imaging by adding the ability to readily visualize vascular anatomy down to the capillary scale. With this level of detail, OCTA can be used to identify many important vascular pathologies such as capillary dropout, microaneurysms, or neovascularization. Because it offers high-resolution, high-contrast imaging of these and similar features, OCTA is useful not just for visualization but also for quantification. Quantification is a powerful feature that enables the potential for diagnostics, staging, evaluation of treatment response, and patient monitoring in a more rigorous way than simple observation. In this review, we will examine several OCTA measurements with either demonstrated clinical utility or clinical potential through the lens of three prevalent blinding diseases: diabetic retinopathy, age-related macular degeneration, and glaucoma. We will discuss the merits of these various measurements and care that should be taken in their interpretation and analyze their role in patient management.},
}
@article {pmid40993448,
year = {2025},
author = {Friedman, SM and Xu, Y and Sherman, S and Kuznik, A and Mojebi, A and Keeping, S and Chan, K and Leng, T and Patel, N},
title = {Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {11},
pages = {2919-2936},
pmid = {40993448},
issn = {2193-8245},
abstract = {INTRODUCTION: Reducing intravitreal injection frequency while maintaining efficacy is a critical goal in alleviating the burden associated with anti-vascular endothelial growth factor (VEGF) therapy in patients with diabetic macular edema (DME) or neovascular age-related macular degeneration (nAMD). In clinical trials, aflibercept 8 mg and faricimab 6 mg administered at extended dosing intervals have demonstrated similar efficacy compared with aflibercept 2 mg, but with fewer injections. This network meta-analysis (NMA) indirectly compared numbers of injections and efficacy between aflibercept 8 mg and faricimab 6 mg administered according to a treat-and-extend (T&amp;E)-based regimen in patients with DME or nAMD.<br><br>METHODS: A systematic literature review was conducted on 10 January 2025, to identify randomized controlled trials of aflibercept 8 mg or faricimab T&amp;E with observation periods of approximately 2 years. Outcomes included number of injections, absolute change from baseline in best-corrected visual acuity (BCVA), and absolute and percentage change from baseline in central subfield thickness (CST). NMAs were performed with Bayesian statistical models. Injection numbers were adjusted to 104 weeks to account for differences in trial observation periods.<br><br>RESULTS: The NMA included 2-year data from six trials: PHOTON, YOSEMITE, and RHINE (DME); and PULSAR, TENAYA, and LUCERNE (nAMD). Treatment with aflibercept 8 mg was associated with significantly fewer injections compared with faricimab T&amp;E in patients with DME (mean difference&#x2009;-3.62 [95% credible interval&#x2009;-4.22,&#x2009;-3.02]) or nAMD (-1.47 [-1.90,&#x2009;-1.05]). Mean changes from baseline in BCVA (absolute) or CST (absolute and percentage) did not differ significantly between the two treatments.<br><br>CONCLUSION: This NMA indicated that aflibercept 8 mg required significantly fewer injections while maintaining similar efficacy over 2 years of treatment compared with faricimab T&amp;E in patients with DME or nAMD.},
}
@article {pmid40991728,
year = {2025},
author = {Gao, F and Tom, E and Rydz, C and Cho, W and Kolesnikov, AV and Sha, Y and Papadam, A and Jafari, S and Joseph, A and Ahanchi, A and Balalaei Someh Saraei, N and Lyon, DC and Foik, A and Nie, Q and Grassmann, F and Kefalov, VJ and Skowronska-Krawczyk, D},
title = {Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice.},
journal = {Science translational medicine},
volume = {17},
number = {817},
pages = {eads5769},
doi = {10.1126/scitranslmed.ads5769},
pmid = {40991728},
issn = {1946-6242},
mesh = {Animals ; *Aging/drug effects ; *Retina/drug effects/metabolism/physiopathology ; *Fatty Acids, Unsaturated/pharmacology/administration &amp; dosage/metabolism/therapeutic use ; Fatty Acid Elongases/metabolism ; *Dietary Supplements ; Mice ; *Vision, Ocular/drug effects ; Mice, Inbred C57BL ; Humans ; Macular Degeneration ; },
abstract = {The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), primarily localized in cell membranes, where they govern membrane biophysical properties. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, which is associated with normal age-related reductions in contrast sensitivity, diminished photoreceptor function and delayed rod-mediated dark adaptation recovery, and pathological age-related macular degeneration (AMD). ELOVL2 (elongation of very long chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs. The methylation status of the ELOVL2 promoter is currently one of the best predictors of chronological age. Here, we show that lower VLC-PUFA abundance in the aged mouse retina is accompanied by a reduction in visual function. Similarly, mice lacking ELOVL2-specific enzymatic activity (Elovl2[C234W]) demonstrate reduced contrast sensitivity and slower rod-mediated dark adaptation. Intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals improved visual function for up to 4 weeks and reduced accumulation of APOE- and C3d-positive sub-RPE deposits. The gene expression pattern observed in supplemented retinas exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature resembling younger retinas. Last, human genetic data from the IAMDGC and UK Biobank linked two variants in the ELOVL2 locus with the onset of intermediate AMD, underlining the translational importance of our findings. Our work highlights VLC-PUFA supplementation as a potential therapeutic opportunity and defines ELOVL2 as a promising target for interventions to prevent age-related vision loss.},
}
@article {pmid40991158,
year = {2025},
author = {Viggiano, P and Accurso Tagano, L and Binetti, R and De Leonardis, S and Carella, M and Ribezzi, G and Termite, AC and Pignataro, MG and Dore, S and Evangelista, F and Evangelista, P and Iaculli, C and Alessio, G and Boscia, F},
title = {Distinct Pathogenic Mechanisms of Neurodegeneration in Pachychoroid Pigment Epitheliopathy Versus Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {11},
pages = {2905-2918},
pmid = {40991158},
issn = {2193-8245},
abstract = {INTRODUCTION: To investigate distinct neurodegeneration mechanisms in pachychoroid pigment epitheliopathy (PPE) versus age-related macular degeneration (AMD) using quantitative optical coherence tomography (OCT) with age-matched controls.<br><br>METHODS: This cross-sectional study of 184 subjects included 50 age-matched controls (25 young: 47-63&#xa0;years; 25 elderly: 67-83&#xa0;years), 57 PPE patients (47-63&#xa0;years), 39 AMD drusen patients (64-80&#xa0;years), and 38 AMD reticular pseudodrusen patients (67-83&#xa0;years). Primary outcomes included ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, subfoveal choroidal thickness, and choroidal volume using swept-source OCT.<br><br>RESULTS: All pathologic conditions showed significant neurodegeneration versus age-matched controls (p&#x2009;<&#x2009;0.001). PPE demonstrated choroidal thickening (410.5&#x2009;&#xb1;&#x2009;32.9&#xa0;&#x3bc;m vs. 306.0&#x2009;&#xb1;&#x2009;10.8&#xa0;&#x3bc;m controls) with inverse choroidal-neural correlations (r&#x2009;=&#x2009;-0.52 to -0.61, p&#x2009;<&#x2009;0.001). AMD variants showed choroidal thinning (187-238&#xa0;&#x3bc;m vs. 277&#xa0;&#x3bc;m elderly controls) with positive correlations (drusen: r&#x2009;=&#x2009;+0.43, p&#x2009;=&#x2009;0.006; RPD: r&#x2009;=&#x2009;+0.68, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Two distinct pathways cause neurodegeneration: compressive (PPE: choroidal thickening&#x2009;&#x2192;&#x2009;choriocapillaris compression&#x2009;&#x2192;&#x2009;neurodegeneration) and ischemic (AMD: choroidal thinning&#x2009;&#x2192;&#x2009;hypoperfusion&#x2009;&#x2192;&#x2009;neurodegeneration).},
}
@article {pmid40990172,
year = {2025},
author = {Gurnani, B and Kaur, K},
title = {Teleophthalmology-enabled devices: bridging the gap in rural eye care.},
journal = {Expert review of medical devices},
volume = {22},
number = {11},
pages = {1167-1172},
doi = {10.1080/17434440.2025.2566741},
pmid = {40990172},
issn = {1745-2422},
mesh = {Humans ; *Telemedicine/instrumentation ; *Ophthalmology/instrumentation/methods ; Rural Population ; Artificial Intelligence ; },
abstract = {INTRODUCTION: Rural populations bear a disproportionate burden of preventable vision loss due to scant ophthalmic resources, long travel distances, and delayed diagnoses of vision-threatening conditions such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Teleophthalmology, leveraging portable imaging devices, data connectivity, and remote interpretation, offers a critical solution by bringing diagnostic capabilities to underserved communities and enabling earlier intervention before irreversible vision loss occurs.<br><br>AREAS COVERED: This report reviews the evolution and performance of handheld fundus cameras and smartphone-based adapters for ophthalmic imaging, as well as portable and home-based OCT systems for high-resolution structural assessment. We summarize key studies that validate device accuracy and examine artificial intelligence algorithms that autonomously grade retinal images with regulatory clearance. We also discuss implementation challenges, including infrastructure gaps, image-quality limitations, cost-utility data, and outline strategies such as hybrid AI-expert workflows, federated learning, and integration of tele-eye care into existing public health programs.<br><br>EXPERT OPINION: Teleophthalmology devices have matured into reliable tools that can democratize eye care. Their success depends on robust digital infrastructure, rigorous device and algorithm validation, and sustainable financing models. Investment in local training, community engagement, and interoperable referral networks is crucial for translating technological advances into meaningful reductions in rural vision impairment.},
}
@article {pmid40989889,
year = {2025},
author = {Zeng, L and Wei, Y and Qiu, Y and Bi, R and Peng, H and Hu, B and Li, Y},
title = {Nanomaterial-Based Anti-Angiogenic Gene Therapy for Retinal Neovascular Diseases: Mechanistic Insights and Preclinical Advances.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {11361-11388},
pmid = {40989889},
issn = {1178-2013},
mesh = {Humans ; *Genetic Therapy/methods ; Animals ; *Retinal Neovascularization/therapy/genetics ; *Nanostructures/chemistry ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Gene Transfer Techniques ; },
abstract = {Retinal neovascular diseases (RNVs) are the leading cause of preventable vision loss worldwide, including diabetic retinopathy, age related macular degeneration, retinopathy of prematurity, and retinal vein occlusion. Anti-VEGF therapy remains central to current clinical management, while emerging molecular targets, including ANG-2, PDGF, Sema4D, integrins, and inflammatory mediators, are gaining therapeutic relevance. The current standard anti-VEGF intravitreal injection (administered every 4-8 weeks) regimen significantly increases the risk of complications such as endophthalmitis and elevated intraocular pressure, which has driven interest in one-time gene therapy approaches. However, traditional viral delivery systems for gene therapy are limited by limited drug loading and poor biocompatibility. This review systematically investigated nanomaterial mediated gene therapy options for anti-angiogenesis in RNVs, focusing on six distinct nanomaterial categories: metal nanoparticles, carbon/silicon nanostructures, lipid nanoparticles, polymers, dendrimers, and nanocomposites. The advantages and limitations of various nanomaterials in terms of gene-loading capacity, controlled release profiles, biocompatibility, and transfection efficiency in the preclinical application of anti-angiogenic gene therapy for RNV diseases were compared. It also provides unique insights into the future multi-target therapy of nanomaterials and hybrid nanomaterial delivery.},
}
@article {pmid40989744,
year = {2025},
author = {Douglas, K and Pardhanani, G and Mariani, L and Chaita, M},
title = {European Health Technology Assessment Considerations Related to Gene Therapies in Eyecare: The Neovascular Age-Related Macular Degeneration Example.},
journal = {Journal of market access &amp; health policy},
volume = {13},
number = {3},
pages = {42},
pmid = {40989744},
issn = {2001-6689},
abstract = {Gene therapies that induce the body to produce therapeutic anti-vascular endothelial growth factor (anti-VEGF) proteins are an emerging topic related to neovascular age-related macular degeneration (nAMD). Continuous delivery of anti-VEGF protein directly to the target tissue offers the possibility of lifelong efficacy without the need for repeated and frequent eye injections. This novel approach could revolutionize patient management through optimizing clinical outcomes while simplifying service delivery. However, such gene therapies are anticipated to face unique challenges related to patients' access and health technology assessment (HTA), and their integration into real-world eyecare practices. This article presents key elements raised at the European Access Academy (EAA) Fall convention (held in Rome in October 2024) regarding anticipated HTA challenges for gene therapies in nAMD. The important role of HTA and policymakers in ensuring that emerging gene therapies are accessible to all eligible patients is also highlighted. This article mainly focuses on the need for a fit-for-purpose EU HTA framework to address the widely varying utilization of standard of care in nAMD clinical practice, and to incorporate considerations about the long-term durability of gene therapies in nAMD. The importance of integrating real-world evidence (RWE) into the EU HTA framework is also discussed.},
}
@article {pmid40989224,
year = {2025},
author = {Benda, PZ and Jakus, G and Sodnik, J and Miljković, N and Tanasković, I and Stokanović, S and Meglič, A and Valentinčič, NV and Mekjavić, PJ},
title = {Reading Assessment and Eye Movement Analysis in Bilateral Central Scotoma Due to Age-Related Macular Degeneration.},
journal = {Journal of eye movement research},
volume = {18},
number = {5},
pages = {38},
pmid = {40989224},
issn = {1995-8692},
abstract = {This study investigates reading performances and eye movements in individuals with eccentric fixation due to age-related macular degeneration (AMD). Overall, 17 individuals with bilateral AMD (7 males; mean age 77.47 ± 5.96 years) and 17 controls (10 males; mean age 72.18 ± 5.98 years) were assessed for reading visual acuity (VA), reading speed (Minnesota low vision reading chart in Slovene, MNREAD-SI), and near contrast sensitivity (Pelli-Robson). Microperimetry (NIDEK MP-3) was used to evaluate preferential retinal locus (PRL) location and fixation stability. Eye movements were recorded with Tobii Pro-glasses 2 and analyzed for reading duration, saccade amplitude, peak velocity, number of saccades, saccade duration, and fixation duration. Individuals with AMD exhibited significantly reduced reading indices (worse reading VA (p < 0.001), slower reading (p < 0.001), and lower near contrast sensitivity (p < 0.001)). Eye movement analysis revealed prolonged reading duration, longer fixation duration, and an increased number of saccades in individuals with AMD per paragraph. The number of saccades per paragraph was significantly correlated with all measured reading indices. These findings provide insights into reading adaptations in AMD. Simultaneously, the proposed approach in analyzing eye movements puts forward eye trackers as a prospective diagnostic tool in ophthalmology.},
}
@article {pmid40987979,
year = {2025},
author = {Biju, BK and Andavar, M},
title = {Resveratrol: potential therapeutic effects on ocular health.},
journal = {Inflammopharmacology},
volume = {33},
number = {10},
pages = {5757-5768},
pmid = {40987979},
issn = {1568-5608},
mesh = {*Resveratrol/pharmacology ; Humans ; Animals ; *Eye Diseases/drug therapy/metabolism ; Oxidative Stress/drug effects ; Antioxidants/pharmacology/therapeutic use ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Stilbenes/pharmacology/therapeutic use ; Inflammation/drug therapy ; },
abstract = {Resveratrol, a polyphenolic compound predominantly found in grapes and red wine, exhibits significant biological activity due to its potent antioxidant and anti-inflammatory properties. Known for its cardioprotective, chemotherapeutic, neuroprotective, and anti-aging effects, resveratrol has garnered attention for its potential in managing age-related ocular diseases, such as glaucoma, cataract, diabetic retinopathy, and macular degeneration-conditions, where oxidative stress and inflammation play central roles in disease progression and vision impairment. Both in vitro and animal studies indicate that resveratrol impacts key biological pathways, including oxidative stress modulation, inflammation reduction, mitochondrial protection, apoptosis regulation, and angiogenesis suppression, which are implicated in the pathology of these ocular conditions. Resveratrol with antioxidant, anti-inflammatory, and anti-angiogenic properties, shows promise in treating ophthalmic diseases by targeting oxidative stress and abnormal angiogenesis, offering a safer, non-invasive alternative to conventional drugs and better scientific validation than herbal remedies. This review synthesizes current research on resveratrol's mechanisms of action, therapeutic potential, and limitations as a treatment for eye disorders, highlighting its promise as a nutritional intervention and areas requiring further exploration.},
}
@article {pmid40987707,
year = {2025},
author = {Yuan, J and Dong, X and Gao, Y and Nao, J},
title = {Pleiotropic regulatory mechanisms and targeted therapeutic prospects of Galectin-3 in aging-related diseases.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {22},
number = {6},
pages = {e00744},
pmid = {40987707},
issn = {1878-7479},
mesh = {Humans ; *Aging/metabolism/drug effects ; *Galectin 3/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/drug therapy ; Diabetes Mellitus, Type 2/metabolism/drug therapy ; Alzheimer Disease/metabolism/drug therapy ; },
abstract = {Aging is a major risk factor for numerous chronic diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), atherosclerosis (AS), type 2 diabetes mellitus (T2DM), osteoarthritis (OA) and age-related macular degeneration (AMD). Galectin-3 (Gal-3), a unique β-galactoside-binding lectin, has emerged as a critical mediator in the pathogenesis of AD and other age-related disorders by modulating key mechanisms such as inflammation, oxidative stress, and apoptosis. While emphasizing neurological disorders (AD, PD), this review also examines Gal-3's role in systemic age-related conditions (T2DM, AS, OA, AMD) that frequently co-occur with or influence neurodegeneration. This review summarizes current knowledge on the expression patterns, molecular mechanisms, and therapeutic potential of Gal-3 in aging-related diseases. Elevated Gal-3 levels have been detected in the brain tissue and cerebrospinal fluid of AD patients, where it contributes to multiple pathological processes, including microglia-driven neuroinflammation, Aβ plaque deposition, tau hyperphosphorylation, oxidative damage, and neuronal apoptosis. Furthermore, Gal-3 upregulation is observed across various age-related diseases and correlates with disease progression, underscoring its potential as a diagnostic biomarker and therapeutic target. Preclinical studies demonstrate that Gal-3-targeted interventions-including small-molecule inhibitors (e.g., TD-139), natural compounds (e.g., modified citrus pectin), and other pharmacological agents-exert neuroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects by binding to Gal-3 and modulating its activity in animal models, offering promising avenues for multi-disease treatment. However, the dual roles and complex regulatory networks of Gal-3 present challenges for clinical translation, requiring context-specific therapeutic approaches tailored to distinct disease mechanisms. Future research should focus on elucidating tissue-specific mechanisms and optimizing combination therapies to enable precise targeting of aging-related pathologies.},
}
@article {pmid40987377,
year = {2025},
author = {Tseng, YH and Wu, PL and Kang, EY and Chen, KJ and Yeh, PH and Yeung, L and Sun, MH and Wang, NK and Hwang, YS and Lai, CC and Wu, WC},
title = {Advancements in ocular blood flow imaging: Clinical applications of laser speckle flowgraphy and optical coherence tomography angiography in retinal and choroidal vascular diseases.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.09.016},
pmid = {40987377},
issn = {1879-3304},
abstract = {Ocular blood flow imaging techniques have become indispensable in current clinical practice because retinal vascular disturbances have been implicated in the pathophysiology of numerous ocular diseases. In this review, we explore the applications of laser Doppler flowmetry, laser speckle flowgraphy (LSFG), and optical coherence tomography angiography (OCTA), focusing on LSFG and OCTA. Each modality is discussed in detail, including its principles, key parameters, advantages, limitations, and common artifacts. We further evaluated their roles in several ocular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy, retinal vein occlusion, retinal artery occlusion, pathologic myopia, glaucoma, non-arteritic anterior ischemic optic neuropathy, and retinopathy of prematurity. Finally, we discuss emerging advancements such as neonatal imaging devices, ultrawide-field OCTA, and artificial intelligence integration in vascular analysis.},
}
@article {pmid40987347,
year = {2025},
author = {Abbas, K and Basilious, A and Duncan, J and Sheidow, T and Hooper, P and Gonder, J},
title = {Transient vision and intraocular pressure changes following anti-vascular endothelial growth factor injection.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2025.09.005},
pmid = {40987347},
issn = {1715-3360},
abstract = {OBJECTIVE: To assess transient intraocular pressure (IOP) and visual acuity (VA) changes following anti-vascular endothelial growth factor (anti-VEGF) injections and explore factors influencing recovery.<br><br>DESIGN: A prospective observational study.<br><br>PARTICIPANTS: Eighty-six patients (100 eyes) receiving anti-VEGF injections with either aflibercept, bevacizumab, or ranibizumab at a retina clinic were included.<br><br>METHODS: Age, biological sex, diagnosis (neovascular age-related macular degeneration, retinal vein occlusion, diabetic macular edema), antiseptic used, anti-VEGF agent, glaucoma status, and IOP-lowering pretreatment were collected. IOP and VA using Snellen charts were measured at baseline, 1, 10, 20, and 30 minutes after injection. Spearman's correlation coefficients were used to assess the relationships between IOP and VA. Ordinal logistic regression was used to evaluate predictors of delayed VA recovery.<br><br>RESULTS: At 1 minute after intravitreal injection (IVI), VA worsened significantly from a baseline of 0.29 &#xb1; 0.21 to 0.76 &#xb1; 0.65 logMAR (p < 0.001), while IOP rose from 14.34 &#xb1; 4.39 mm Hg to 54.53 &#xb1; 20.21 mm Hg (p < 0.001). VA progressively improved over time, with 43% of eyes returning to baseline at 1 minute, 67% at 10 minutes, 83% at 20 minutes, and 89% at 30 minutes. The Spearman correlation coefficient for VA and IOP was statistically significant at 1-minute follow-up after IVI at 0.244 (p&#x202f;=&#x202f;0.014) but not at later follow-ups. Eyes returning to baseline VA at 1 minute exhibited lower IOP than those not at baseline (p&#x202f;=&#x202f;0.0004). Logistic regression revealed no significant predictors of delayed VA recovery.<br><br>CONCLUSIONS: Worsened VA and elevated IOP are common in the immediate postinjection period with later improvement. Patients' awareness of VA fluctuations within the first 30 minutes postinjection may aid in the early detection and management of complications associated with IOP elevation.},
}
@article {pmid40983489,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Pan, Z and Wu, X and Wang, YX},
title = {Photoreceptor layer thickness in age-related macular degeneration: the Beijing Eye Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2024-326734},
pmid = {40983489},
issn = {1468-2079},
abstract = {PURPOSE: To assess the photoreceptor layer thickness and its associations with age-related macular degeneration (AMD).<br><br>METHODS: Participants of the population-based Beijing Eye Study without optic nerve or retinal diseases (except for early and intermediate AMD) were examined by optical coherence tomography of the macula.<br><br>RESULTS: The study cohort was composed of 2426 participants (mean age: 62.8&#xb1;9.1 years; range: 50-93 years), with 200 and 393 individuals affected by early AMD and intermediate AMD, respectively. In multivariable analysis, thickness of Henle's fibre layer, outer nuclear layer, external limiting membrane and myoid zone (HOEM) combined was not significantly associated with AMD prevalence (beta: 0.03; p=0.08) or AMD stage (beta: 0.04; p=0.06), after adjusting for younger age (beta: -0.09; p<0.001), shorter axial length (beta: -0.07; p<0.001), thicker ellipsoid zone (EZ) (beta: 0.19; p<0.001), thicker photoreceptor outer segment (POS) layer (beta: 0.12; p<0.001), thicker subfoveal choroid (beta: 0.11; p<0.001) and thinner retinal pigment epithelium/Bruch's membrane (RPE/BM) layer (beta: -0.17; p<0.001). Thicker EZ correlated with lower AMD prevalence (beta: -0.04; p=0.03) and lower AMD stage (beta: -0.02; p=0.02), with adjustment for older age (beta: 0.05; p=0.03), longer axial length (beta: 0.06; p=0.001), thicker HOEM (beta: 0.19; p<0.001) and thinner RPE/BM (beta: -0.31; p<0.001). Including only normal eyes and eyes with early AMD, EZ thickness was not significantly correlated with AMD prevalence (beta: -0.02; p=0.49). Thicker POS correlated with lower AMD prevalence (beta: -0.06; p<0.001) after adjusting for younger age (beta: -0.10; p<0.001), thicker HOEM (beta: 0.08; p<0.001) and thinner RPE/BM layer (beta: -0.62; p<0.001). If only normal eyes and eyes with early AMD were included, POS thickness was not significantly related to AMD prevalence (beta: -0.03; p=0.09).<br><br>CONCLUSIONS: Thickness of HOEM, EZ and POS was not significantly associated with the prevalence of early AMD.},
}
@article {pmid40983254,
year = {2025},
author = {Jonas, JB and Jonas, RA and Panda-Jonas, S},
title = {Clinical and histological aspects of the anatomy of myopia, myopic macular degeneration and myopia-associated optic neuropathy.},
journal = {Progress in retinal and eye research},
volume = {109},
number = {},
pages = {101402},
doi = {10.1016/j.preteyeres.2025.101402},
pmid = {40983254},
issn = {1873-1635},
abstract = {Axial myopia is characterized by a panoply of morphological, clinical and histological, features in association with longer axial length. It includes changes in the region peripheral to the optic nerve head (reduction in the density of photoreceptors and retinal pigment epithelium (RPE) cells and retinal thinning); in the optic nerve head region in moderately myopic eyes (shift of Bruch's membrane (BM) opening typically in the temporal/inferior direction, leading to a secondary BM overhang into the nasal intrapapillary compartment, BM absence in the temporal parapapillary region ("gamma zone"), and optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter; and widening of the RPE opening leading to myopic parapapillary beta zone), and in highly myopic eyes (BM opening enlargement resulting in a circular gamma zone, elongation and thinning of the lamina cribrosa ("secondary macrodisc") and of the peripapillary scleral flange ("parapapillary delta zone"); and in the macular region with an elongation of the fovea-optic disc distance, reduction in angle kappa, straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers (leading to a re-arrangement of the retinal nerve fibers with a myopia-specific regional distribution of the retinal nerve fiber layer thickness profile), choroidal thinning most pronounced at the posterior pole and affecting mainly the medium-sized and large choroidal vessel layer), and scleral thinning. Pathologic changes in the macular region are extrafoveally located, linear RPE layer defects (lacquer cracks), potentially widening to round RPE layer defects (patchy atrophies), in some eyes with central BM defects; BM defects with RPE layer defects in the foveal region, accompanied by macular neovascularization or subsequent subretinal RPE cell proliferation ("macular atrophy"); myopic macular retinoschisis; and staphylomas. With longer axial length, the prevalence of non-glaucomatous optic neuropathy and glaucoma-like/glaucomatous optic neuropathy steeply increases beyond an axial length of 26.0-26.5 mm. With BM thickness being independent of axial length and in view of eye shape change from an oblate or sphere in emmetropia to a prolate rotational ellipsoid in myopia, the myopia specific morphological changes may be associated with a primary BM enlargement in the region peripheral to the optic disc.},
}
@article {pmid40983165,
year = {2025},
author = {Quarta, A and Feo, A and Corradetti, G and Popovic, MM and Sadda, SR},
title = {Double layer sign in chorioretinal diseases: Clinical significance and implications from multimodal imaging.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.09.017},
pmid = {40983165},
issn = {1879-3304},
abstract = {The double-layer sign (DLS) is an emerging optical coherence tomography (OCT) biomarker of growing diagnostic and prognostic relevance in retinal and chorioretinal diseases, including age-related macular degeneration, pachychoroid spectrum disorders. Multimodal imaging, particularly OCT angiography (OCTA), has enhanced our ability to characterize DLS and its role in disease progression and treatment response. DLS is identified as a separation between the retinal pigment epithelium (RPE) and Bruch's membrane, with overlapping phenotypic presentations including flat irregular pigment epithelial detachment (FIPED) and shallow irregular retinal pigment epithelial elevation. These signs are often associated with vascularized lesions that demonstrate increased DLS thickness, irregular contours, and heterogeneous reflectivity. OCTA offers superior sensitivity and specificity for detecting subclinical macular neovascularization compared to dye-based angiography, which may underestimate nonexudative neovascularization. Additionally, indocyanine green angiography remains crucial for identifying branching vascular networks and polypoidal lesions, especially in polypoidal choroidal vasculopathy. In pachychoroid diseases, such as chronic central serous chorioretinopathy, the presence of FIPED/DLS can indicate underlying neovascularization, which may benefit from combination therapy with anti-vascular endothelial growth factor agents. We discuss the multimodal imaging characteristics, prognostic significance, and clinical relevance of DLS across various retinal and chorioretinal disorders.},
}
@article {pmid40977621,
year = {2025},
author = {Sommer-Lind, F and Subhi, Y and Vergmann, AS and Lövestam-Adrian, M and Andersen, N and Borrelli, E and Cehofski, LJ and Falk, MK and Jørstad, &#xd8;K and Kaarniranta, K and Kaya, MY and Larsen, MB and Reiter, GS and Schneider, M and Vorum, H and Grauslund, J and , },
title = {Consensus on age-related macular degeneration course curricula for general ophthalmologists and non-ophthalmologist clinical staff: A Delphi study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70006},
pmid = {40977621},
issn = {1755-3768},
support = {24030031//Synoptik-Fonden/ ; 24090018//Synoptik-Fonden/ ; },
abstract = {PURPOSE: To define the curriculum content for two interactive learning courses on age-related macular degeneration (AMD): (1) an advanced course tailored for general ophthalmologists and (2) a basic course for non-ophthalmologist healthcare staff. This initiative aims to establish a national consensus on the educational framework for AMD management among general ophthalmologists in Denmark.<br><br>METHODS: We conducted a three-round Delphi study. The Delphi panel consisted of 33 ophthalmologists (28 retinal specialists from Denmark and five internationally recognized retinal specialists), eight non-ophthalmologist healthcare staff (six optometrists, one ophthalmic nurse and one clinic assistant) with experience in managing patients with AMD. To ensure national representation, we recruited panel participants from all five Danish regions.<br><br>RESULTS: Response rates were 85%, 73% and 71% for Delphi rounds 1, 2 and 3, respectively. In the first round, participants suggested a total of 390 potential curriculum components and learning goals: 211 components for the advanced course and 179 for the basic course. After the third round, the panel reached consensus on an AMD curriculum, which included 46 topics for the advanced course (e.g., OCT interpretation: signs of disease activity versus atrophic changes) and 15 topics for the basic course (e.g., visual requirements for driving).<br><br>CONCLUSION: This study reached consensus on the curricula for courses on AMD for general ophthalmologists and non-ophthalmologist healthcare staff. This forms the basis for developing instructional, virtual, interactive courses that can support the development and maintenance of competencies related to AMD, both in Denmark and abroad.},
}
@article {pmid40977307,
year = {2025},
author = {Cinque, F and Pas, J and Shahabi, M and Sluijterman, L and Ten Brink, S and de Breuk, A and Heesterbeek, TJ and Klaver, C and Hoyng, C and Lechanteur, Y},
title = {Power and clinical utility of mesopic microperimetry analysis strategies in age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70008},
pmid = {40977307},
issn = {1755-3768},
support = {//Bayer/ ; //Stichting Steunfonds Uitzicht/ ; //Gelderse Blindenstichting/ ; //Stichting Blindenhulp/ ; //Louise Rottinghuisfonds/ ; },
abstract = {PURPOSE: This study evaluates whether mesopic microperimetry (MMP) provides a more robust measure of retinal function compared to visual acuity (VA) in age-related macular degeneration (AMD) clinical trials, with a focus on optimal analysis strategies.<br><br>METHOD: Fellow-eyes of unilateral neovascular AMD were prospectively studied. Presenting VA was measured. The Macular Integrity Assessment Microperimeter (MAIA) was used with a 4 to 2 staircase strategy with a 10&#xb0; diameter grid containing 37 loci. Three analysis strategies were calculated: the mean of 37 sensitivity thresholds (MS), the per cent reduced threshold (PRT), and the log-transformed candela mean (MS cd log). Sample size requirements were calculated for 12- and 24-month follow-ups using a paired one-sided T-test (&#x3b1;&#x2009;=&#x2009;0.05, power&#x2009;=&#x2009;0.80).<br><br>RESULTS: N&#x2009;=&#x2009;123 were analysed (82 (65.5%) females; mean age 74.2 (7.8) years). Ranked high to low, the required sample size at 12&#x2009;months was: MS (n&#x2009;=&#x2009;51), MS cd log (n&#x2009;=&#x2009;52), PRT (n&#x2009;=&#x2009;139), and VA (n&#x2009;=&#x2009;203). Similar trends were seen at 24&#x2009;months, with MS requiring the smallest sample size (n&#x2009;=&#x2009;85) and VA the largest (n&#x2009;=&#x2009;1673).<br><br>CONCLUSION: All MMP analysis strategies outperformed VA, and MS required the least number of patients to show significant changes. This trend was consistent for both 12 and 24&#x2009;months. These findings provide strong statistical arguments for the use of MMP in longitudinal within-subjects clinical trials and suggest that averaging decibels is optimal.},
}
@article {pmid40976965,
year = {2025},
author = {Fei, Y and Jin, Z and He, L and Zhang, M and Jiao, Q and Liu, Q and Lin, F and Wang, W and Wang, N and Cao, A and Cheng, D},
title = {Homozygous FAT1 frameshift mutation linked to glomerulotubular nephropathy with impaired cell adhesion and Rap1 signaling.},
journal = {Renal failure},
volume = {47},
number = {1},
pages = {2561216},
pmid = {40976965},
issn = {1525-6049},
mesh = {Humans ; Female ; *Frameshift Mutation ; Adult ; Cell Adhesion/genetics ; Homozygote ; Signal Transduction/genetics ; *Cadherins/genetics/metabolism ; Exome Sequencing ; *Kidney Diseases/genetics ; *rap1 GTP-Binding Proteins/metabolism ; },
abstract = {Genetic mutations are closely linked to various renal diseases, revealing important molecular mechanisms that contribute to kidney dysfunction. Here, we reported a 35-year-old Chinese female diagnosed of glomerulotubular nephropathy with multiple extra-renal manifestations including ptosis, corneal dystrophy, macular degeneration, right foot syndactyly. Whole-exome sequencing identified a homozygous frameshift variant in FAT1 (NM_005245: c.7444_7445delGT, p.Val2482AsnfsTer16). Further analysis revealed that this mutation caused translation repression of FAT1. RNA sequencing showed dysregulation of cell adhesion and Rap1 signaling pathways, while immunofluorescence staining demonstrated disrupted β-catenin junctions and cytoskeletal abnormalities in patient-derived primary urinary epithelial cells. Pull-down assays indicated that the reduction in activated Rap1 levels was correlated with the observed cellular defects. These findings provide compelling evidence that this loss-of-function homozygous FAT1 variant is causally associated with nephropathy and congenital anomalies, likely through degradation of transcribed mRNA and impaired protein expression. The results emphasize the critical role of FAT1 in renal development and provide new insights into the molecular mechanisms underlying these conditions.},
}
@article {pmid40976557,
year = {2025},
author = {McKay, BS and Grabrucker, AM and Thompson, RB and Chew, EY and Lengyel, I and González-Iglesias, H},
title = {Zinc in eye health, retinal biology and disease.},
journal = {Progress in retinal and eye research},
volume = {109},
number = {},
pages = {101404},
doi = {10.1016/j.preteyeres.2025.101404},
pmid = {40976557},
issn = {1873-1635},
abstract = {Zinc is an essential trace mineral that plays a crucial role in numerous bodily functions, including immune response, wound healing, and protein synthesis. Regarding eye health, zinc is particularly important due to its high concentration, functional abundance, and critical roles in the retina/RPE/choroid complex, where both deficiency and excess can lead to cellular dysfunction. This mineral contributes significantly to the maintenance of the structure and function of the tissues, and it is believed to help protect against oxidative stress, which can damage cells in the eye. The retinal pigment epithelium/choroid complex (RPE/choroid) contains the highest zinc concentration. Therefore, it is unsurprising that several eye disorders associated with this interface are associated with reduced zinc accumulation, and zinc supplementation has become an essential secondary preventive therapy for diseases like age-related macular degeneration (AMD). Despite zinc's importance in health and diseases of the outer retina, it still needs to be fully understood how zinc participates in cellular and molecular events and how zinc supplementation might be beneficial. However, it appears that adequate zinc levels are essential for retinal health and overall vision, particularly as we age. This review is focused on summarising our current understanding of the biology of zinc, with particular attention paid to the RPE/choroid interface.},
}
@article {pmid40975892,
year = {2025},
author = {Yan, R and Wang, Y and Wang, Y and Pang, M and Wei, L and Zhu, M and Yang, H and Yu, W},
title = {Bioengineering Approaches for the 3D Blood-Retinal Barrier: Disease Modeling and Drug Development.},
journal = {ACS biomaterials science &amp; engineering},
volume = {11},
number = {10},
pages = {5740-5755},
doi = {10.1021/acsbiomaterials.5c00706},
pmid = {40975892},
issn = {2373-9878},
mesh = {Humans ; *Blood-Retinal Barrier/drug effects/metabolism ; Animals ; *Drug Development ; *Bioengineering/methods ; *Retinal Diseases/drug therapy/pathology ; Printing, Three-Dimensional ; Tissue Scaffolds/chemistry ; },
abstract = {The integrity and functionality of the blood-retina barrier (BRB) are essential for maintaining homeostasis of the retina. Disruption of the BRB is a key feature in different stages of retinal diseases including diabetic retinopathy, age-related macular degeneration (AMD), and inherited retinal diseases such as retinitis pigmentosa. In order to understand and recapitulate various retinal diseases, there has been significant interest in the progress of in vitro 3D-BRB models as they may address limitations associated with traditional 2D cultures and xenogeneic animal models. Therefore, it is crucial to explore 3D in vitro models for investigating mechanistic and therapeutic strategies in BRB-related diseases. In this review, we provide an overview of recent advances in BRB models, ranging from simple constructs to complex systems. In this review, commonly used techniques (extracellular matrix scaffolds, 3D bioprinting, and microfluidics), cell types utilized, and biomaterials employed are discussed. Additionally, we focus on new developments over the past three years, emphasizing applications of 3D-BRB models in disease evolution and drug screening. Overall, 3D modeling for the BRB holds promise for recapitulating the structural and functional characteristics of the in vivo BRB, which is a powerful armament for laboratory research and translational medicine for retinal diseases.},
}
@article {pmid40975596,
year = {2025},
author = {Yiu, G},
title = {Using Natural Language Processing to Score Age-Related Macular Degeneration Severity.},
journal = {Ophthalmology},
volume = {132},
number = {10},
pages = {1088-1090},
doi = {10.1016/j.ophtha.2025.06.012},
pmid = {40975596},
issn = {1549-4713},
}
@article {pmid40975484,
year = {2025},
author = {Yang, Q and Govindarajan, V and Li, Q and Zhou, H and Shaikh, ZA and Ksibi, A and Yang, J and Por, LY},
title = {OcuMDNet: A lightweight CNN for robust multi-disease retinal diagnosis with cross-dataset reliability.},
journal = {Experimental eye research},
volume = {261},
number = {},
pages = {110642},
doi = {10.1016/j.exer.2025.110642},
pmid = {40975484},
issn = {1096-0007},
mesh = {Humans ; *Neural Networks, Computer ; Reproducibility of Results ; *Retinal Diseases/diagnosis ; ROC Curve ; Diabetic Retinopathy/diagnosis ; Macular Degeneration ; Fundus Oculi ; Glaucoma/diagnosis ; *Diagnostic Techniques, Ophthalmological ; },
abstract = {This study aims to develop a lightweight convolutional network for the classification of multiple retinal diseases using fundus images and to evaluate cross-dataset generalization under strict label alignment. We introduce OcuMDNet (Ocular Multi-Disease Net), a compact convolutional neural network (CNN) specifically designed for fundus imagery, incorporating batch normalization and dropout for regularization. A standardized processing pipeline is employed, which includes cropping and resizing images to 224 × 224 pixels, applying contrast-limited adaptive histogram equalization (CLAHE), and performing per-channel normalization. The training process utilizes the AdamW optimizer and incorporates early stopping to enhance model performance. We propose a label-aligned evaluation protocol: (i) assesses 4-class performance (Normal, diabetic retinopathy (DR), Glaucoma, age-related macular degeneration (AMD)) on a combined dataset assembled from public sources; (ii) reports disease-specific results based on the native labels of each dataset (DR: EyePACS, Messidor; Glaucoma: ORIGA; AMD: AREDS); and (iii) evaluates cross-dataset transfer for DR (training on EyePACS and testing on Messidor). Patient-level splits are implemented to prevent data leakage, and class counts are reported for each split. Performance metrics such as accuracy, macro-F1 score, and one-vs-rest ROC-AUC are calculated with 95 % confidence intervals using stratified bootstrap (n = 1000). Paired comparisons are conducted using McNemar's test for accuracy and DeLong's method for AUC, with multiplicity control applied. The OcuMDNet demonstrates strong performance on both combined and disease-specific benchmarks, maintaining robust discrimination in cross-dataset evaluations for DR while ensuring computational efficiency suitable for large-scale screening applications. Ablation studies confirm the significance of preprocessing steps and architectural choices. In conjunction with a label-aligned protocol, the OcuMDNet provides an accurate and efficient baseline for multi-disease fundus analysis, facilitating a transparent assessment of cross-dataset reliability. The code, scripts, and trained weights will be made available to support reproducibility.},
}
@article {pmid40975441,
year = {2025},
author = {Lee, E and Hunt, D and Cakir, Y and Kuo, D and Zhou, Z and Pajic, M and Hadziahmetovic, M},
title = {Artificial intelligence in age-related macular degeneration: Advancing diagnosis, prognosis, and treatment.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.09.007},
pmid = {40975441},
issn = {1879-3304},
support = {R21 EY033480/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. While anti-vascular endothelial growth factor (anti-VEGF) therapy and novel treatments for geographic atrophy have improved management, timely diagnosis and personalized intervention remain a challenge. Artificial intelligence (AI), such as machine learning and deep learning models, shows promise in AMD diagnosis, classification, and treatment planning. This review summarizes AI's recent advancements, highlights its clinical utility, and addresses key limitations for wider real-world implementation in AMD. We conducted systematic search of PubMed from its conception up to August 1, 2024. Studies utilizing AI-based algorithms for AMD management were identified and categorized into early detection/classification and prediction of disease progression/treatment response. Data extraction focused on AI model performance, imaging modalities, and clinical applicability. Of 193 records screened, 47 studies were included, in which 19 studies focused on early detection/classification and 28 on prediction of disease progression/treatment response. AI models demonstrated high accuracy in AMD classification and progression prediction, including in real-world settings. Prediction models for treatment response, particularly anti-VEGF therapy, could provide recommendations on optimizing injection timelines. Recent studies have also begun tackling previous challenges, such as algorithmic biases, limited generalizability, and AI's "black-box" nature. AI-based models offer significant potential to transform AMD care through timely detection and personalized treatment; however, clinical integration depends on improving model interpretability and validating tools across diverse populations. As AI continues to evolve, ongoing research is needed to refine AI models and support their translation into evidence-based, real-world applicability in AMD.},
}
@article {pmid40974049,
year = {2025},
author = {Hsiung, CN and Chou, WC and Hsu, CH and Chen, L},
title = {Genome-wide association study reveals genetic mechanisms underlie eye disorders and comorbidities.},
journal = {HGG advances},
volume = {7},
number = {1},
pages = {100520},
pmid = {40974049},
issn = {2666-2477},
abstract = {Eye diseases, including cataracts, glaucoma, diabetes retinopathy, and age-related macular degeneration, are major global health challenges and leading causes of blindness. This study leveraged genome-wide association studies (GWASs) involving over 100,000 individuals, integrating data from the Taiwan Biobank and National Health Insurance Research Database, to identify genetic loci associated with disease onset. Our findings suggest that these conditions are influenced by multifactorial etiologies, as pleiotropic loci including rs10811660, rs4710941, rs2283228, and rs7646518 were identified, linking ocular diseases to metabolic conditions. Notably, a strong genetic correlation was observed between cataract and depression. Mendelian randomization analysis further demonstrated a causal effect of depression on cataract risk, implicating shared biological pathways, particularly oxytocin signaling, in disease pathophysiology. This finding revealed a functional genetic variant near the OXTR gene, highlighting its potential as a causal candidate for genetic diagnosis in precision health. By bridging the gap between genetic discovery and clinical application, this research offers critical insights into shared genetic mechanisms across diverse health domains, paving the way for innovative diagnostic and therapeutic strategies.},
}
@article {pmid40973913,
year = {2025},
author = {Ahmed, F and Uddin, MDJ},
title = {OcuViT: A Vision Transformer-Based Approach for Automated Diabetic Retinopathy and AMD Classification.},
journal = {Journal of imaging informatics in medicine},
volume = {},
number = {},
pages = {},
pmid = {40973913},
issn = {2948-2933},
abstract = {Early detection and accurate classification of retinal diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), are essential to preventing vision loss and improving patient outcomes. Traditional methods for analyzing retinal fundus images are often manual, prolonged, and rely on the expertise of the clinician, leading to delays in diagnosis and treatment. Recent advances in machine learning, particularly deep learning, have introduced automated systems to assist in retinal disease detection; however, challenges such as computational inefficiency and robustness still remain. This paper proposes a novel approach that utilizes vision transformers (ViT) through transfer learning to address challenges in ophthalmic diagnostics. Using a pre-trained ViT-Base-Patch16-224 model, we fine-tune it for diabetic retinopathy (DR) and age-related macular degeneration (AMD) classification tasks. To adapt the model for retinal fundus images, we implement a streamlined preprocessing pipeline that converts the images into PyTorch tensors and standardizes them, ensuring compatibility with the ViT architecture and improving model performance. We validated our model, OcuViT, on two datasets. We used the APTOS dataset to perform binary and five-level severity classification and the IChallenge-AMD dataset for grading age-related macular degeneration (AMD). In the five-class DR and AMD grading tasks, OcuViT outperforms all existing CNN- and ViT-based methods across multiple metrics, achieving superior accuracy and robustness. For the binary DR task, it delivers highly competitive performance. These results demonstrate that OcuViT effectively leverages ViT-based transfer learning with an efficient preprocessing pipeline, significantly improving the precision and reliability of automated ophthalmic diagnosis.},
}
@article {pmid40973777,
year = {2025},
author = {Hogg, HDJ and Talks, SJ and Engelmann, J and Teare, MD and Pogose, M and Patel, PJ and Balaskas, K and Maniatopoulos, G and Keane, PA},
title = {Dual site external validation of artificial intelligence-enabled treatment monitoring for neovascular age-related macular degeneration in England.},
journal = {Eye (London, England)},
volume = {39},
number = {16},
pages = {2973-2979},
pmid = {40973777},
issn = {1476-5454},
support = {NIHR301467//DH | National Institute for Health Research (NIHR)/ ; },
mesh = {Humans ; *Artificial Intelligence ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; England ; *Angiogenesis Inhibitors/therapeutic use ; Aged ; Male ; Female ; Intravitreal Injections ; Ranibizumab/therapeutic use ; Aged, 80 and over ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Subretinal Fluid ; },
abstract = {BACKGROUND: Monitoring neovascular age-related macular degeneration (nAMD) is a significant contributor to ophthalmology demands in the NHS, with clinical capacity struggling to meet the demand. This task depends upon interpreting retinal optical coherence tomography (OCT) imaging, where artificial intelligence (AI) could rebalance clinical demand and capacity. However, evidence of safety and effectiveness in nAMD monitoring is lacking.<br><br>METHODS: Using a published non-inferiority design protocol, 521 pairs of ipsilateral retinal OCTs from consecutive visits for nAMD treatment were collected from two NHS ophthalmology services. Real-world binary assessments of nAMD disease activity or stability were compared to an independent ophthalmic reading centre reference standard. An AI system capable of retinal OCT segmentation analysed the OCTs, applying thresholds for intraretinal and subretinal fluid to generate binary assessments. The relative negative predictive value (rNPV) of AI versus real-world assessments was calculated.<br><br>RESULTS: Real-world assessments of nAMD activity showed a NPV of 81.6% (57.3-81.6%) and a positive predictive value (PPV) of 41.5% (17.8-62.3%). Optimised thresholds for intraretinal fluid increase (>1,000,000&#x2009;&#xb5;m&#xb3;) and subretinal fluid increase (>2,000,000&#x2009;&#xb5;m&#xb3;) for the AI system assessments produced an NPV of 95.3% (85.5-97.9%) and PPV of 57.8% (29.4-76.0%). The rNPV of 1.17 (1.11-1.23) met predefined criteria for clinical and statistical superiority and accompanied an rPPV of 1.39 (1.10-1.76).<br><br>CONCLUSIONS: This study suggests that the same thresholds for interpreting OCT-based AI analysis could reduce undertreatment and overtreatment in nAMD monitoring at different centres. Interventional research is needed to test the potential of supportive or autonomous AI assessments of nAMD disease activity to improve the quality and efficiency of services.},
}
@article {pmid40971067,
year = {2025},
author = {Borselli, M and Elfalah, M and Trunfio, TA and Scala, A and Chisari, D and Mancini, A and Lucisano, A and Carnovale-Scalzo, G and Mollace, V and Improta, G and Zweifel, S and Scorcia, V and Toro, MD and Carnevali, A},
title = {Neovascular Age-Related Macular Degeneration Treated with Aflibercept: Five-Year Follow-Up and Correlation with Optical Coherence Tomography Biomarkers in a Real-World Setting.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {11},
pages = {2831-2848},
pmid = {40971067},
issn = {2193-8245},
abstract = {INTRODUCTION: To evaluate long-term outcomes of neovascular age-related macular degeneration(nAMD) treatment with aflibercept in a treat-and-extend (T&amp;E) regimen and explore correlations between optical coherence tomography (OCT) biomarkers and clinical evolution over 5 years in a real-world setting.<br><br>METHODS: This retrospective monocentric study included patients diagnosed with type 1 or type 2 nAMD at the University Magna Graecia of Catanzaro between 2016 and 2024. Inclusion criteria were treatment-na&#xef;ve status, diagnosis confirmed by OCT and optical coherence tomography angiography (OCT-A), exclusive treatment with intravitreal aflibercept following a T&amp;E regimen, and a minimum 5-year follow-up. Best-correct visual acuity (BCVA) and OCT were assessed at baseline, after the third injection, and yearly up to year 5 (seven time points). Evaluated OCT biomarkers included subretinal and intraretinal fluid (SRF, IRF), hyperreflective spots (HS), drusenoid pigment epithelial detachment (dPED), subretinal hyperreflective material (SHRM), outer retinal tubulations (ORT), onion sign, retinal pigment epithelium (RPE) tears, and subretinal fibrosis.<br><br>RESULTS: Among 59 cases, 57.6% were type 1 macular neovascularization (MNV) and 42.4% type 2. At the baseline, SRF was more common in type 1, SHRM in type 2. Central foveal thickness (CFT) decreased significantly in both groups after loading and remained stable. SRF decreased significantly in type 1 (p&#x2009;=&#x2009;0.001), but not in type 2. dPED decreased in both groups, significantly in type 1 (p&#x2009;=&#x2009;0.01). HS decreased in patients&#xa0;with type 1 MNV (p&#x2009;=&#x2009;0.009). RPE tears were more frequent in type 2 (12%) and linked to BCVA loss. For type 2 MNV, ORT (p&#x2009;=&#x2009;0.035) and subretinal fibrosis appeared from year 5 (p&#x2009;=&#x2009;0.006). BCVA improved after loading in both groups, declined after year 2, and was better preserved in those with better visual acuity after the loading dose.<br><br>CONCLUSIONS: Baseline SHRM in type 2 MNV may predict more IRF, ORT, and RPE tears over time. Type 1 MNV with baseline SRF often shows reduced HS and dPED but may develop subretinal fibrosis. BCVA gains after loading wane by year 5, and eyes needing ongoing treatment for persistent OCT biomarkers decline gradually in both subtypes (significant in type 1).},
}
@article {pmid40971062,
year = {2025},
author = {Bartolomeo, N and Schuetz, YP and Nascimbeni, AC and Castro, DG and Crozat, B and Barry, MP and Ambresin, A},
title = {Early Outcome Analysis of Intravitreal Aflibercept 8 mg Treatment in Naïve Patients with Neovascular Age-Related Macular Degeneration Using Artificial Intelligence.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {11},
pages = {2819-2829},
pmid = {40971062},
issn = {2193-8245},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is one of the leading causes of vision loss, often requiring frequent injections. Our aim is to report the early outcomes of intravitreal aflibercept (IVA) 8 mg treatment in naïve patients with nAMD.<br><br>METHODS: An observational, retrospective, monocentric study was conducted at Swiss Visio Montchoisi, Lausanne, Switzerland. A total of 51 eyes of 48 patients with na&#xef;ve macular neovascularization (MNV) secondary to AMD received a loading phase of three-monthly IVA followed by a monthly observational phase until fluid recurrence. At each visit, all patients had a full ophthalmological exam, including spectral-domain optical coherence tomography (SD-OCT), which was analysed manually and with artificial intelligence (AI). The main outcomes were best-corrected visual acuity (BCVA), central subfield thickness (CST), maximal pigment epithelial detachment (PED) height, presence or absence of intraretinal fluid (IRF) and subretinal fluid (SRF) on SD-OCT, and mean volumetric changes in IRF, SFR, and PED using AI at baseline and month 1, 2, 3, and 6.<br><br>RESULTS: Mean age at baseline was 79.94&#x2009;&#xb1;&#x2009;7.29&#xa0;years, and 81.25% of patients were female. At baseline, mean BCVA was 70.44&#x2009;&#xb1;&#x2009;12.48 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, mean CST was 339.8&#x2009;&#xb1;&#x2009;174.6.0&#xa0;&#x3bc;m, and mean Maximal PED height was 214.3&#x2009;&#xb1;&#x2009;115.1&#xa0;&#x3bc;m. After loading and at month 6, BCVA significantly increased by 2.47 and 3.41 ETDRS letters, respectively. Mean CST and PED height significantly decreased to 231.9&#x2009;&#xb1;&#x2009;68.69&#xa0;&#x3bc;m and 137.6&#x2009;&#xb1;&#x2009;68.53&#xa0;&#x3bc;m, respectively, at month 6. Qualitative and AI-quantified biomarkers significantly decreased after loading and at month 6. A mean interval of 9.67&#x2009;&#xb1;&#x2009;3.87&#xa0;weeks was reached with a mean number of 4.63&#x2009;&#xb1;&#x2009;1.01 injections at the time of the last observation. Baseline IRF and HRF were negative predictors of functional outcomes in the short term. One patient with sterile vitritis benefited from vitrectomy and topical treatment.<br><br>CONCLUSIONS: Aflibercept intravitreal injections in the treatment of na&#xef;ve patients with wet AMD demonstrated rapid improvement of functional and anatomical parameters, particularly regarding fluid control and quantitative biomarkers on OCT. A comprehensive analysis of follow-up visits will be performed to confirm our early results.},
}
@article {pmid40971061,
year = {2025},
author = {Kuznik, A and Coughlan, A and Pinsent, A and Toro-Diaz, H and Sherman, S and Patel, N},
title = {Economic Benefit of Aflibercept 8 mg Versus Faricimab for Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema in the US.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {11},
pages = {2863-2875},
pmid = {40971061},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this study was to compare the estimated direct and indirect costs with aflibercept 8 mg and faricimab in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) over 5 years.<br><br>METHODS: An economic model was developed to estimate direct and indirect costs based on the mean number of injections administered in clinical trials of aflibercept 8&#xa0;mg (PULSAR and PHOTON) and faricimab (TENAYA/LUCERNE and YOSEMITE/RHINE). Injection numbers for years 1 and 2 were sourced from clinical trials, injection numbers in years 3-5 were imputed from year 2, and the base case for the analysis was a 3-year time horizon. Direct costs were estimated based on modeled mean injection numbers and 2025 wholesale acquisition costs per injection (aflibercept 8&#xa0;mg: 2677.50 USD; faricimab: 2289.65 USD) plus medical monitoring costs. Indirect costs included caregiver and patient time and travel costs.<br><br>RESULTS: Over a 3-year time horizon, the mean number of injections was lower with aflibercept 8&#xa0;mg versus faricimab for nAMD (12.25 vs. 14.80 injections) and DME (11.80 vs. 15.65 injections). Total costs (direct and indirect) associated with aflibercept 8&#xa0;mg were 1978.74 USD lower than faricimab for nAMD and 6032.90 USD lower than faricimab for DME. After year 1, similar differences were seen through 5&#xa0;years.<br><br>CONCLUSIONS: For both nAMD and DME, less frequent dosing with aflibercept 8&#xa0;mg versus faricimab is expected to reduce the direct and indirect cost burden to payers and patients.},
}
@article {pmid40970870,
year = {2025},
author = {Romano, F and Casaluci, M and Valastro, A and Airaldi, M and Milella, P and Pozzo Giuffrida, F and Cozzi, E and Aretti, A and Teo, KY and Cheung, CMG and Nassisi, M and Viola, F and Staurenghi, G and Invernizzi, A},
title = {Ten-Year Incidence, Risk Factors and Progression Rate of Macular Atrophy in Neovascular Age-Related Macular Degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.14608},
pmid = {40970870},
issn = {1442-9071},
abstract = {BACKGROUND: To evaluate the 10-year cumulative incidence, progression rates, and risk factors for macular atrophy (MA) in neovascular age-related macular degeneration (nAMD) patients receiving long-term anti-vascular endothelial growth factor (VEGF) therapy.<br><br>METHODS: Retrospective, multicenter, cohort study including 148 eyes from 140 nAMD patients treated with a pro-re-nata (PRN) anti-VEGF regimen and followed for &#x2265;&#x2009;10&#x2009;years. Annual multimodal imaging-including blue autofluorescence [BAF], spectral-domain optical coherence tomography [SD-OCT] and near-infrared reflectance-was reviewed to detect and quantify MA using RegionFinder. Kaplan-Meier analysis estimated cumulative MA incidence, while mixed-effects Cox and linear regressions identified risk factors and progression rates.<br><br>RESULTS: Baseline MA prevalence was 23.0%, increasing to 64.9% at 5&#x2009;years and 79.8% at 10&#x2009;years. Foveal involvement occurred in 47.4% of cases. Significant predictors for MA included baseline BCVA <&#x2009;20/40 (HR&#x2009;=&#x2009;1.50, p&#x2009;=&#x2009;0.02), greater central subfield thickness (CST) fluctuations (HR&#x2009;=&#x2009;1.04, p&#x2009;=&#x2009;0.01), and more frequent submacular haemorrhages (HR&#x2009;=&#x2009;1.34, p&#x2009;=&#x2009;0.04). Type 3 macular neovascularization was associated with fovea-involving MA (HR&#x2009;=&#x2009;2.03, p&#x2009;=&#x2009;0.02). Mean MA size increased from 0.34 to 2.27&#x2009;mm at 10&#x2009;years, progressing at 0.20&#x2009;mm/year (&#x3b2;&#x2009;=&#x2009;0.15, p&#x2009;<&#x2009;0.001). Eyes with incident MA exhibited faster progression (&#x3b2;&#x2009;=&#x2009;0.03, p&#x2009;=&#x2009;0.01) and worse BCVA decline compared to those with baseline MA (-1.96 vs. -1.42 letters/year, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: nAMD patients treated with PRN anti-VEGF therapy demonstrated a high 10-year cumulative incidence of MA (79.8%), with poor baseline BCVA and CST fluctuations as key risk factors. Eyes with incident MA progressed faster and were associated with greater visual decline, suggesting a more visually impactful atrophy.},
}
@article {pmid40970575,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX},
title = {Prevalence and associations of the three-layer sign in age-related macular degeneration. The Beijing eye study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70004},
pmid = {40970575},
issn = {1755-3768},
support = {82271086//National Natural Science Foundation of China/ ; 82571275//National Natural Science Foundation of China/ ; },
abstract = {OBJECTIVE: To assess the prevalence and associations of the detectability of the three-layer sign (TLS) in a general population, including individuals with age-related macular degeneration (AMD) or without any retinal disease.<br><br>METHODS: Using OCT images running horizontally through the foveola of participants of the population-based Beijing Eye Study, we assessed the TLS detectability. We defined the TLS as the visibility of the ellipsoid zone (EZ), interdigitation zone and retinal pigment epithelium (RPE)/Bruch's membrane line as separate units in the foveola on optical coherence tomographic (OCT) images.<br><br>RESULTS: The study included 1566 eyes (age: 65.3&#x2009;&#xb1;&#x2009;9.8&#x2009;years; axial length: 23.01&#x2009;&#xb1;&#x2009;0.93&#x2009;mm; range: 19.90&#x2009;mm-28.93&#x2009;mm), randomly selected within each group of normal eyes (n&#x2009;=&#x2009;592; 37.8%), eyes with early AMD (n&#x2009;=&#x2009;700; 44.7%), intermediate AMD (n&#x2009;=&#x2009;267; 17.0%), and late AMD (n&#x2009;=&#x2009;7; 0.4%). In the normal group, TLS prevalence decreased with older age (OR: 0.93; p&#x2009;<&#x2009;0.001), declining from 217/265 (81.9%) in the 50-59&#x2009;years age group to 57/126 (45.2%) in individuals aged 70+ years. In the whole study cohort, TLS prevalence decreased (p&#x2009;<&#x2009;0.001) from 389/592 (65.7%) in the normal group to 334/700 (47.7%), 66/267 (24.7%) and 0/7 (0%) in early AMD, intermediate AMD and late AMD, respectively. In multivariable analysis, higher TLS prevalence was associated with younger age (OR: 0.92; p&#x2009;<&#x2009;0.001), female sex (OR: 1.65; p&#x2009;<&#x2009;0.001), lower AMD stage (OR: 0.51; p&#x2009;<&#x2009;0.001), better best-corrected visual acuity (OR: 0.42; p&#x2009;=&#x2009;0.03), and lower prevalence of a flat retinal pigment epithelium elevation (OR: 0.68; p&#x2009;=&#x2009;0.04).<br><br>CONCLUSIONS: The foveal TLS may be taken as a qualitative sign of the intactness of the deep layers of the fovea, with its prevalence decreasing with older age, higher AMD stage and worse best-corrected visual acuity.},
}
@article {pmid40970447,
year = {2025},
author = {Abdulrazzaq, GM and Merkhan, MM and Billa, N and Alany, RG and Amoaku, WM and Tint, NL and Ahmad, Z and Qutachi, O},
title = {Current and emerging therapies for dry and neovascular age-related macular degeneration.},
journal = {Pharmaceutical development and technology},
volume = {30},
number = {8},
pages = {1147-1182},
doi = {10.1080/10837450.2025.2562196},
pmid = {40970447},
issn = {1097-9867},
mesh = {Humans ; *Macular Degeneration/drug therapy/pathology ; *Angiogenesis Inhibitors/therapeutic use ; Animals ; Oxidative Stress/drug effects ; *Choroidal Neovascularization/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Disease Progression ; },
abstract = {Age-related macular degeneration (AMD), first identified in the 1840s, is now considered the leading cause of visual impairment in elderly people in Western societies. This condition affects the macula, a region rich with photoreceptors essential for detailed visual resolution and colour vision. Advanced AMD can be either atrophic (dry) or exudative (wet), and both forms may coexist. Exudative AMD is characterised by choroidal neovascularisation, where abnormal blood vessels invade the retina and the retinal pigment epithelium (RPE), leading to fluid accumulation in sub- and intra-retinal compartments and photoreceptor dysfunction. In contrast, atrophic AMD involves the gradual degeneration of the RPE and outer retinal layers. Current treatments, such as anti-vascular endothelial growth factor (anti-VEGF) therapies for exudative AMD, can slow or halt disease progression but do not offer a cure. Over the past decade, extensive research programs have focused on various pathogenetic mechanisms of AMD, including oxidative stress, inflammation, and complement pathway dysregulation. This review aims to highlight current theories for developing new treatments, compile recent discoveries and insights into AMD pathogenesis and disease progression, and place special emphasis on therapeutic approaches that have reached clinical trials, evaluating their findings wherever possible.},
}
@article {pmid40970228,
year = {2025},
author = {Salabati, M and Garrigan, H and Momenaei, B and Wakabayashi, T and Wong, JC and Patel, D and Mahmoudzadeh, R and Mansour, HA and Ammar, M and Xu, D and Regillo, CD},
title = {Clinical Characteristics and Long-Term Outcomes of Eyes With Neovascular Age-Related Macular Degeneration Requiring Frequent Treatment.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251371007},
pmid = {40970228},
issn = {2474-1272},
abstract = {Purpose: To compare long-term visual outcomes in neovascular age-related macular degeneration (AMD) patients who received frequent vs infrequent antivascular endothelial growth factor injections. Methods: This retrospective case series included treatment-naïve AMD patients receiving either frequent injections (≤ 6-week intervals) or infrequent injections (≥ 10-week intervals). Best-available visual acuity (VA) and anatomic outcomes were assessed at the initial visit, 52 weeks, 104 weeks, and final visit. Results: A total of 151 eyes were studied over a mean follow-up of 42.6 months: 81 eyes (54%) in the frequent group and 70 eyes (46%) in the infrequent group. Baseline central foveal thickness (CFT) was higher in the frequent group (320 µm vs 265 µm; P = .002). Though CFT improved in both groups, it remained higher in the frequent group at 52 weeks (230 µm vs 185 µm; P = .004), 104 weeks (203 µm vs 173 µm; P = .004), and final visit (197 µm vs 165 µm; P = .015). The frequent group showed more subretinal and intraretinal fluid at all times. Baseline logMAR VA was 0.63 and 0.84 in the frequent and infrequent groups, respectively (P = .10). Visual improvement was similar between groups at 52 weeks (0.21 vs 0.22 logMAR; P = .916), 104 weeks (0.21 vs 0.18 logMAR; P = .714), and final visit (0.1 vs 0.05 logMAR; P = .510). Poor baseline VA (P < .001) and geographic atrophy (P = .025) were associated with worse outcomes. Conclusions: Over 4 years, despite higher CFT and more fluid, frequent injections showed similar visual improvement to infrequent injections. Baseline vision was the strongest predictor of final outcomes, regardless of injection frequency.},
}
@article {pmid40970089,
year = {2025},
author = {Doncheva, D and Eden, ER and Futter, CE},
title = {Specialised features of melanosomes in health and disease in the retinal pigment epithelium.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1593840},
pmid = {40970089},
issn = {2296-634X},
abstract = {This mini-review focuses on melanosome biogenesis, positioning and function in the retinal pigment epithelium (RPE) where melanosomes absorb light scatter and protect against the harmful effects of photo-oxidation. RPE melanosomes share a common biogenesis pathway with those of skin melanocytes but are made primarily embryonically and are retained by the RPE throughout life. They do however move from the cell body into the apical processes which, in mammalian RPE, is regulated by a machinery related to that regulating melanosome distribution in skin melanocytes. Melanosomes in the RPE make extensive membrane contacts with the ER and mitochondria although their role in adult RPE remains to be fully established. Albinism is associated with multiple visual defects and reduced or absent pigmentation in melanosomes has implications for long term visual health. Age-related changes in melanosomes have been implicated in retinal degenerative disease, including age-related macular disease (AMD). The lysosomes of the RPE have an unparalleled degradative burden arising from the daily phagocytosis of the distal tips of photoreceptor outer segments, which is part of a daily process of outer segment renewal. A failure to fully process the phagocytosed outer segments leads to a build-up of the toxic ageing pigment, lipofuscin, which accumulates in all ageing RPE. Melanolipofuscin also accumulates in the RPE with age and may result from melanin-mediated degradation of lipofuscin through melanin chemiexcitation. Age-related loss of melanosome-mediated protection could be an important component of age-related visual decline.},
}
@article {pmid40969489,
year = {2025},
author = {Chen, Q and Keenan, TDL and Agron, E and Allot, A and Guan, E and Duong, B and Elsawy, A and Hou, B and Xue, C and Bhandari, S and Broadhead, G and Cousineau-Krieger, C and Davis, E and Gensheimer, WG and Golshani, CA and Grasic, D and Gupta, S and Haddock, L and Konstantinou, E and Lamba, T and Maiberger, M and Mantopoulos, D and Mehta, MC and Elnahry, AG and Al-Nawaflh, M and Oshinsky, A and Powell, BE and Purt, B and Shin, S and Stiefel, H and Thavikulwat, AT and Wroblewski, KJ and Chung, TY and Cheung, CMG and Cheng, CY and Chew, EY and Hribar, MR and Chiang, MF and Lu, Z},
title = {Towards Accountable AI in Eye Disease Diagnosis: Workflow, External Validation, and Development.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {40969489},
issn = {2331-8422},
support = {R00 LM014024/LM/NLM NIH HHS/United States ; },
abstract = {IMPORTANCE: Timely disease diagnosis is challenging due to limited clinical availability and growing burdens. Although artificial intelligence (AI) shows expert-level diagnostic accuracy, a lack of downstream accountability-including workflow integration, external validation, and further development- continues to hinder its real-world adoption.<br><br>OBJECTIVE: To address gaps in the downstream accountability of medical AI through a case study on age-related macular degeneration (AMD) diagnosis and severity classification.<br><br>We developed and evaluated an AI-assisted diagnostic and classification workflow for AMD. Four rounds of diagnostic assessments (accuracy and time) were conducted with 24 clinicians from 12 institutions. Each round was randomized and alternated between Manual and Manual + AI, with a washout period. In total, 2,880 AMD risk features were evaluated across 960 images from 240 Age-Related Eye Disease Study patient samples, both with and without AI assistance. For further development, we enhanced the original DeepSeeNet model into DeepSeeNet+ using ~40,000 additional images from the US population and tested it on three datasets, including an external set from Singapore.<br><br>MAIN OUTCOMES AND MEASURES: We measured the F1-score for accuracy (Wilcoxon rank-sum test) and diagnostic time (linear mixed-effects model), comparing Manual vs. Manual + AI. For further development, the F1-score (Wilcoxon rank-sum) was again used.<br><br>RESULTS: Among the 240 patients (mean age, 68.5 years; 53% female), AI assistance improved accuracy for 23 of 24 clinicians, increasing the average F1-score by 20% (37.71 to 45.52), with some improvements exceeding 50%. Manual diagnosis initially took an estimated 39.8 seconds per patient, whereas Manual + AI saved 10.3 seconds and remained 1.7-3.3 seconds faster in later rounds. However, combining manual and AI may not always yield the highest accuracy or efficiency, underscoring challenges in explainability and trust. DeepSeeNet+ performed better in three test sets, achieving 13% higher F1-score in the Singapore cohort.<br><br>CONCLUSIONS AND RELEVANCE: In this diagnostic study, AI assistance improved both accuracy and time efficiency for AMD diagnosis. Further development was essential for enhancing AI generalizability across diverse populations. These findings highlight the need for downstream accountability during early-stage clinical evaluations of medical AI. All code and models are publicly available.},
}
@article {pmid40969487,
year = {2025},
author = {Wu, P and Lin, M and Chen, Q and Chew, EY and Lu, Z and Peng, Y and Dong, H},
title = {AMD-Mamba: A Phenotype-Aware Multi-Modal Framework for Robust AMD Prognosis.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {40969487},
issn = {2331-8422},
support = {R21 EY035296/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, making effective prognosis crucial for timely intervention. In this work, we propose AMD-Mamba, a novel multi-modal framework for AMD prognosis, and further develop a new AMD biomarker. This framework integrates color fundus images with genetic variants and socio-demographic variables. At its core, AMD-Mamba introduces an innovative metric learning strategy that leverages AMD severity scale score as prior knowledge. This strategy allows the model to learn richer feature representations by aligning learned features with clinical phenotypes, thereby improving the capability of conventional prognosis methods in capturing disease progression patterns. In addition, unlike existing models that use traditional CNN backbones and focus primarily on local information, such as the presence of drusen, AMD-Mamba applies Vision Mamba and simultaneously fuses local and long-range global information, such as vascular changes. Furthermore, we enhance prediction performance through multi-scale fusion, combining image information with clinical variables at different resolutions. We evaluate AMD-Mamba on the AREDS dataset, which includes 45,818 color fundus photographs, 52 genetic variants, and 3 socio-demographic variables from 2,741 subjects. Our experimental results demonstrate that our proposed biomarker is one of the most significant biomarkers for the progression of AMD. Notably, combining this biomarker with other existing variables yields promising improvements in detecting high-risk AMD patients at early stages. These findings highlight the potential of our multi-modal framework to facilitate more precise and proactive management of AMD.},
}
@article {pmid40967511,
year = {2025},
author = {Lewallen, CF and Ortolan, D and Reichert, D and Sharma, R and Bharti, K},
title = {Impact of artificial intelligence in vision science: A systematic review of progress, emerging trends, data domain quantification, and critical gaps.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.09.014},
pmid = {40967511},
issn = {1879-3304},
abstract = {The prominence of artificial intelligence (AI) is growing exponentially, yet its implementation across research domains is uneven. To quantify AI trends in vision science, we evaluated over 100,000 PubMed article metadata spanning 35 years. Using Medical Subject Headings (MeSH) terms, we analyzed trends across four prominent ocular diseases: age-related macular degeneration, diabetic retinopathy, glaucoma, and cataract. Most articles utilized research techniques from at least one of the following domains: biological models, molecular profiling, image-based analysis, and clinical outcomes. Our quantification reveals that AI prominence is disproportionally concentrated in the image-based analysis domain, and, additionally, among 4 diseases evaluated, AI prevalence in cataract research is lagging. Contributing factors towards these disparities include insufficient data standardization, complex data structures, limited data availability, unresolved ethical concerns, and not gaining meaningful improvements over human-based interpretations. By mapping where AI thrives and where it lags, we offer a quantitative reference for funding agencies, clinicians, and vision scientists. Connecting various research domains with multimodal and generative AI could improve diagnostic utility; enabling earlier diagnosis, personalized therapy, reduced healthcare costs, and accelerate innovation. Future work should move AI in vision science beyond image-centric pattern recognition toward integrative, mechanistic analyses that explain - rather than merely detect - disease.},
}
@article {pmid40967488,
year = {2025},
author = {Holz, FG and Ziemssen, F and Bauer-Steinhusen, U and Wachtlin, J and Schürks, M and Lorenz, K and Scholz, P and Machewitz, T and Rech, C and Lanzl, I and Lommatzsch, A and Finger, RP and , },
title = {Adherence to Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: 24-Month Results from the ANDROMEDA Study.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.09.004},
pmid = {40967488},
issn = {2468-6530},
abstract = {PURPOSE: The ANDROMEDA (intravitreal Aflibercept in Neovascular amD: an obseRvational study assessing patient relevant OutcoMes, rEal-worlD treatment pattern And effectiveness) study was planned to assess adherence to intravitreal aflibercept (IVT-AFL) 2 mg treatment over 24 months for neovascular age-related macular degeneration (nAMD) and to identify patient- and physician-related factors for nonadherence (NA) in clinical settings.<br><br>DESIGN: Prospective, observational, noncontrolled, multicenter cohort study.<br><br>SUBJECTS: Treatment-na&#xef;ve and previously treated adult patients with nAMD under IVT-AFL treatment from 41 centers in Germany.<br><br>METHODS: Time to first occurrence of NA was analyzed descriptively using Kaplan-Meier methods followed by a Cox model to explore the potential impact of patient- and physician-related factors on NA. Participants reported reasons for NA in standardized telephone interviews.<br><br>MAIN OUTCOME MEASURES: Primary endpoints were time to first occurrence of and reasons for NA. Secondary endpoints included change in best-corrected visual acuity and central retinal thickness from baseline to months 4, 12, and 24.<br><br>RESULTS: The median time to first NA was 180 days in the 509 study participants (mean age: 77.2 years; 57.2% female). Among them, 44.0% were treatment-na&#xef;ve, 22.6% were previously treated with IVT-AFL, and 33.4% were previously treated with other anti-VEGF agents (VEGF). Adherence rates, particularly among treatment-na&#xef;ve participants, fell early and markedly: 69.6% at 4 months (95% confidence interval [CI]: 62.9%-75.3%), 53.0% at 12 months (95% CI: 46.0%-59.5%), and 40.1% at 24 months (95% CI: 33.3%-46.9%). Key risk factors for NA (hazard ratio [HR] <1 indicating a higher risk of NA for the mentioned factor, HR > 1 indicating a lower risk for the mentioned factor) included presence of any "other diseases" in the treatment-na&#xef;ve cohort at baseline (HR: 0.57; 95% CI: 0.37-0.88), and patient-reported "lack of information for accompanying persons" (HR: 1.36; 95% CI: 1.03-1.79), involvement of referrals and multiple providers (HR: 0.76; 95% CI: 0.60-0.97), and "bilateral AMD" (HR: 0.73; 95% CI: 0.57-0.93) in the total cohort.<br><br>CONCLUSIONS: In the ANDROMEDA study, key determinants of NA were comorbidities, bilateral disease, treatment by multiple providers, and a lack of patient caregiver education. Thus, better adherence may be achieved through holistic patient management, considering additional disease parameters, single-center treatment, and improved (caregiver) education.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40966958,
year = {2025},
author = {Kuo, PH and Du, E and Huang, CJ and Lan, WC and Chou, SH and Yao, TC and Peng, CC},
title = {Improvement of an eye disease detection model by using the denoising diffusion implicit model.},
journal = {Computational biology and chemistry},
volume = {120},
number = {Pt 2},
pages = {108677},
doi = {10.1016/j.compbiolchem.2025.108677},
pmid = {40966958},
issn = {1476-928X},
abstract = {With rapid developments in artificial intelligence (AI), the discussion about and applications of generative AI have increased substantially. Generative AI has extensive and valuable applications in many industrial and medical fields and is a possible solution for industries that struggle to collect large quantities of data. The present study evaluated the use of generative AI in eye disease prediction. Because retinal images are difficult to acquire, this study used a generative AI model [i.e., the denoising diffusion implicit model (DDIM)] to conduct data augmentation, thereby improving the accuracy of a convolutional neural network (CNN) model developed for eye disease detection. This study adopted the DDIM primarily for its high inference speed and ability to consistently generate high-quality samples in a limited number of steps, making it suitable for tasks that require high-quality medical images. With the increasing prevalence of electronic products, the number of patients with retinopathy or optic neuropathy is increasing annually, and patients are experiencing these diseases at increasingly younger ages. Moreover, eye diseases such as glaucoma and macular degeneration are becoming increasingly common in modern society. The developed CNN model exhibited a 3 % higher accuracy when it was trained using the data generated by the DDIM than when it was trained without these data. This CNN model can screen eye disease symptoms early to enable patients to receive timely treatment, thereby mitigating the risk and consequences of eye diseases. The results of this study indicate that the training data generated using the DDIM can enhance the accuracy of early eye disease detection.},
}
@article {pmid40965880,
year = {2025},
author = {Liu, SH and Mandava, N and Li, T},
title = {Metformin and Age-Related Macular Degeneration-No Causal Evidence Yet.},
journal = {JAMA ophthalmology},
volume = {143},
number = {10},
pages = {853-854},
doi = {10.1001/jamaophthalmol.2025.3183},
pmid = {40965880},
issn = {2168-6173},
}
@article {pmid40965862,
year = {2025},
author = {Jindal, DA and Hanna, J and Shaia, JK and Markle, J and Rachitskaya, A and Kaelber, DC and Singh, RP and Talcott, KE},
title = {Metformin and the Development of Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {143},
number = {10},
pages = {844-853},
pmid = {40965862},
issn = {2168-6173},
mesh = {Humans ; *Metformin/therapeutic use ; Aged ; Female ; Male ; *Hypoglycemic Agents/therapeutic use ; Aged, 80 and over ; Disease Progression ; *Wet Macular Degeneration/diagnosis/prevention &amp; control/epidemiology ; Electronic Health Records ; Retrospective Studies ; Risk Factors ; *Geographic Atrophy/diagnosis ; *Macular Degeneration/diagnosis ; Cohort Studies ; Diabetes Mellitus, Type 2/drug therapy ; },
abstract = {IMPORTANCE: Metformin has demonstrated protective effects in systemic diseases, including cancer, cardiovascular disease, and retinal diseases, such as diabetic retinopathy and choroidal neovascularization. Literature suggests metformin may reduce the risk of age-related macular degeneration (AMD), but a consensus has not been reached.<br><br>OBJECTIVE: To evaluate the association of metformin with the development of any AMD and progression to geographic atrophy and neovascular AMD using a large electronic health record (EHR) platform.<br><br>This cohort study had 2 exposed cohorts of participants aged 65 years or older who were prescribed metformin: one without AMD to assess development of any AMD and the other with mild or moderate nonexudative AMD to evaluate AMD progression to geographic atrophy or neovascular AMD. Corresponding nonexposed cohorts consisted of participants not prescribed metformin. Participants were required to meet inclusion criteria at least 6 months before the outcome of interest occurred. Those who had outcomes of interest before meeting inclusion criteria were excluded from analysis. This cohort study used a federated health research platform aggregating deidentified EHR data from 70 institutions (TriNetX). Data were collected from January 2013 to June 2025 and analyzed from September 2024 to June 2025.<br><br>EXPOSURES: Participants prescribed metformin.<br><br>MAIN OUTCOMES AND MEASURES: Propensity score matching controlled for confounders, such as age, sex, race, hypertension, diabetes, and other systemic conditions. Risk ratios (RRs) with 95% CIs were calculated to compare outcomes at 5 years, 10 years, and any time after meeting criteria. Any confidence intervals that crossed 0.90 to 1.10 were considered statistically not significant. Comparisons between exposed and unexposed groups were repeated requiring a diagnosis of cataract.<br><br>RESULTS: Before propensity score matching, cohort 1 (no AMD) included 297&#x202f;008 participants exposed to metformin (mean [SD] age, 74.9 [7.0] years; 157&#x202f;584 [53.1%] female) and 1&#x202f;269&#x202f;644 participants unexposed to metformin (mean [SD] age, 76.8 [7.9] years; 738&#x202f;640 [58.2%] female). Before propensity score matching in cohort 2 (early or intermediate nonexudative AMD), there were 12&#x202f;843 participants exposed to metformin (mean [SD] age, 79.5 [7.2] years; 7107 [55.3%] female) and 77&#x202f;279 participants unexposed to metformin (mean [SD] age, 81.6 [7.2] years; 48&#x202f;491 [62.7%] female). After propensity score matching, participants prescribed metformin had comparable risk of developing any AMD relative to those not prescribed metformin (RR, 0.90; 95% CI, 0.86-0.94). When stratified by time, the risk remained similar at 5 years (RR, 0.94; 95% CI, 0.90-0.99) and 10 years (RR, 0.91; 95% CI, 0.87-0.94). Similarly, participants prescribed vs not prescribed metformin had a comparable risk of AMD progression over these time spans (RR for geographic atrophy, 0.87; 95% CI, 0.76-1.01; RR for neovascular AMD, 1.03; 95% CI, 0.91-1.17).<br><br>CONCLUSION AND RELEVANCE: This study suggests that, overall, metformin is not associated with significant development or progression of AMD. Further studies and prospective analyses are necessary to evaluate whether dosage and longevity of metformin use are associated with AMD development or progression.},
}
@article {pmid40965406,
year = {2025},
author = {Villafuerte-Trisolini, C and Le, SM and Sin, TN and Huynh, L and Gong, M and Shen, T and Heo, J and Roszak, K and Raposo, AS and Graham, J and Havel, P and Choy, K and Farsiu, S and Thomasy, SM and Yiu, G},
title = {Systemic and Local Lipids in Nonhuman Primates With Drusen and Age-Related Maculopathies.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {12},
pages = {41},
pmid = {40965406},
issn = {1552-5783},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; P30 EY012576/EY/NEI NIH HHS/United States ; R01 EY032238/EY/NEI NIH HHS/United States ; U24 EY029904/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Macaca mulatta ; *Retinal Drusen/metabolism/pathology/blood/diagnosis ; *Macular Degeneration/metabolism/pathology/blood/diagnosis ; Tomography, Optical Coherence ; *Lipids/blood ; Male ; Female ; Retinal Pigment Epithelium/metabolism/ultrastructure ; Fluorescein Angiography ; Disease Models, Animal ; },
abstract = {PURPOSE: Lipids are a principal component of drusen and are involved in the pathobiology of age-related macular degeneration (AMD). Nonhuman primates (NHPs) develop macular drusen and may provide insight into circulating or local lipids in AMD.<br><br>METHODS: We evaluated aged rhesus macaques by fundus photography, optical coherence tomography (OCT), and fundus autofluorescence, as well as measured fasting plasma glucose, total cholesterol, high- and low-density lipoproteins, triglycerides, and apolipoprotein (Apo) A1, B, CIII, and E. Retinal tissues were collected for electron microscopy and immunostained for oil red O, ApoE, and ApoB.<br><br>RESULTS: Among 203 adult macaques (mean age 19.1 &#xb1; 3.1 years), 25 animals (12.1%) exhibited soft drusen with sub-RPE deposits, while 59 (28.6%) had yellow punctate dots that were mostly hyperautofluorescent without RPE elevation on OCT. Drusen prevalence increased with older age (P = 0.001) but not with plasma lipids (P > 0.05 for all), while the punctate dot phenotype was associated with older age (P = 0.014), higher fasting glucose (P = 0.023), low-density lipoprotein cholesterol (P = 0.022), and ApoB (P = 0.017). Ultrastructure revealed NHP drusen consisting of extracellular sub-RPE lipid particles, whereas punctate dots appeared to correspond to individual RPE cells with intracellular lipid vacuoles. Both sub-RPE and intra-RPE lipids of the two phenotypes contained neutral lipids and ApoE, while ApoE and ApoB appeared to be expressed in RPE.<br><br>CONCLUSIONS: In rhesus macaques, soft drusen are extracellular lipid deposits associated with older age, while punctate dots are intracellular lipids linked to age, hyperglycemia, and hyperlipidemia, suggesting differential dysregulation of lipid transport in these NHP models of AMD.},
}
@article {pmid40965251,
year = {2025},
author = {Lonfat, N and Moreno-Leon, L and Punzo, C and Khanna, H},
title = {Update on Gene Therapy Clinical Trials for Eye Diseases.},
journal = {Human gene therapy},
volume = {36},
number = {19-20},
pages = {1287-1300},
doi = {10.1177/10430342251379824},
pmid = {40965251},
issn = {1557-7422},
mesh = {Humans ; *Genetic Therapy/methods ; Clinical Trials as Topic ; Genetic Vectors/genetics ; *Eye Diseases/therapy/genetics ; Gene Editing ; Dependovirus/genetics ; Gene Transfer Techniques ; Macular Degeneration/therapy/genetics ; Animals ; },
abstract = {Inherited and complex retinal degenerative diseases, such as retinitis pigmentosa, age-related macular degeneration, and glaucoma, represent a significant global burden of irreversible vision loss. Due to immense genetic and clinical heterogeneity and complex underlying mechanisms, these diseases still lack safe and effective disease-modifying treatments. This review summarizes the current landscape of gene therapeutic approaches to develop novel treatments for these blinding conditions. Specifically, we provide an update on several ongoing or completed clinical trials on gene-specific or gene-agnostic approaches, including recombinant adeno-associated viral vector-mediated delivery of the full gene or gene editing and antisense oligonucleotide components into the eye. We also discuss the initial clinical trial results of the use of the different approaches to ocular delivery, including subretinal, intravitreal, and suprachoroidal delivery. While long-term clinical trial data and refined clinical endpoints are essential to assess the efficacy, safety, and durability of these strategies, the data so far underscore the immense potential of gene therapy to revolutionize the management of retinal diseases in patients living with these debilitating conditions.},
}
@article {pmid40965041,
year = {2025},
author = {Eidenberger, A and Reiter, GS and Mares, V and Frank-Publig, S and Fuchs, P and Baratsits, M and Gumpinger, M and Faustmann, G and Miere, A and Creuzot-Garcher, C and Scheschy, U and Kodjikian, L and Gualino, V and Wolff, B and Sacu, S and Schmidt-Erfurth, U},
title = {Fluid/function correlation using AI-based quantification versus central subfield thickness in treatment-naïve and pre-treated patients with neovascular AMD in a real-world setting.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70000},
pmid = {40965041},
issn = {1755-3768},
abstract = {PURPOSE: To investigate the association between best-corrected visual acuity (BCVA) and quantitative macular fluid volumes, compared to central subfield thickness (CST) in treatment-naïve and previously treated patients with active neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSIS: Baseline data were collected from 290 eyes of 290 participants consecutively enrolled in a prospective, randomized phase III clinical trial. Intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) volumes were quantified and localized using an MDR-certified AI algorithm (Fluid Monitor, RetInSight). Fluid volumes and CST were included in linear regression models for comparison.<br><br>RESULTS: Significantly greater IRF volumes within each macular region were observed in treatment-na&#xef;ve patients, whereas larger PED volumes contributed to higher CST values in pretreated patients. In both subgroups, the largest proportion of BCVA variance could be explained by measuring IRF and SRF volumes within the entire 6-mm area (adjusted R[2]&#x2009;=&#x2009;0.140 and 0.225, respectively). In pre-treated eyes, CST explained only half as much BCVA variance as the 6-mm fluid model, and the model's fit was even poorer when compared to the CST model in the treatment-na&#xef;ve subgroup (adjusted R[2]&#x2009;=&#x2009;0.078 vs. 0.198).<br><br>CONCLUSION: The examination of IRF and SRF volumes significantly impacts BCVA in nAMD. The weaker association of CST highlights its limitations as a parameter of disease activity. These findings emphasize the necessity of distinct fluid volume quantification as a relevant surrogate for visual function loss or benefit in nAMD, with particular emphasis on treatment duration and fluid in regions beyond the central 1-mm.},
}
@article {pmid40964624,
year = {2024},
author = {Bo, N and Wei, Y and Zeng, L and Kang, C and Ding, Y},
title = {A Meta-Learner Framework to Estimate Individualized Treatment Effects for Survival Outcomes.},
journal = {Journal of data science : JDS},
volume = {22},
number = {4},
pages = {505-523},
pmid = {40964624},
issn = {1680-743X},
support = {R01 GM141076/GM/NIGMS NIH HHS/United States ; },
abstract = {One crucial aspect of precision medicine is to allow physicians to recommend the most suitable treatment for their patients. This requires understanding the treatment heterogeneity from a patient-centric view, quantified by estimating the individualized treatment effect (ITE). With a large amount of genetics data and medical factors being collected, a complete picture of individuals' characteristics is forming, which provides more opportunities to accurately estimate ITE. Recent development using machine learning methods within the counterfactual outcome framework shows excellent potential in analyzing such data. In this research, we propose to extend meta-learning approaches to estimate individualized treatment effects with survival outcomes. Two meta-learning algorithms are considered, T-learner and X-learner, each combined with three types of machine learning methods: random survival forest, Bayesian accelerated failure time model and survival neural network. We examine the performance of the proposed methods and provide practical guidelines for their application in randomized clinical trials (RCTs). Moreover, we propose to use the Boruta algorithm to identify risk factors that contribute to treatment heterogeneity based on ITE estimates. The finite sample performances of these methods are compared through extensive simulations under different randomization designs. The proposed approach is applied to a large RCT of eye disease, namely, age-related macular degeneration (AMD), to estimate the ITE on delaying time-to-AMD progression and to make individualized treatment recommendations.},
}
@article {pmid40963925,
year = {2025},
author = {Chen, Y and Bounds, SE and Kundu, N and Karmoker, JR and Liu, Y and Kim, D and Cai, J},
title = {Role of MiR-204 in controlling metabolic functions of the subretinal microglia.},
journal = {Theranostics},
volume = {15},
number = {17},
pages = {8952-8963},
pmid = {40963925},
issn = {1838-7640},
support = {P30 EY021725/EY/NEI NIH HHS/United States ; R01 EY026999/EY/NEI NIH HHS/United States ; R01 EY034742/EY/NEI NIH HHS/United States ; R01 EY035855/EY/NEI NIH HHS/United States ; },
mesh = {*MicroRNAs/genetics/metabolism ; Animals ; *Microglia/metabolism ; Mice ; Mice, Knockout ; *Retinal Pigment Epithelium/metabolism ; Lipid Metabolism/genetics ; Extracellular Vesicles/metabolism ; *Retina/metabolism ; Mice, Inbred C57BL ; },
abstract = {Rationale: MicroRNA-204 (miR-204) is one of the most abundant miRNA species in the retinal pigment epithelium (RPE) and RPE-derived extracellular vesicles (EVs). Knockout (KO) of miR-204 leads to dysfunction and degeneration of both the RPE and the retina. In addition to previously reported retinal pathologies, we observed the accumulation of lipid-laden subretinal microglia in miR-204 KO mice. This study aimed to identify potential molecular targets of miR-204 involved in microglia lipid processing and to determine whether RPE-derived EVs can improve the function of miR-204-deficient retinal microglia. Methods: Lipid accumulation in microglia was detected by staining with LipidTox, a fluorescent dye specific for neutral lipids, followed by either flow cytometry analysis or direct visualization on RPE/choroid flat mounts. MiRNA database and target prediction tools, such as miRWalk and TargetScan, were used to search for potential target genes of miR-204 in microglia. The identified target mRNA was validated with a miRNA reporter assay. RPE EVs were prepared from ex vivo cultured mice eye cups and administered via retro-orbital injection in miR-204 knockout (KO) mice. RPE integrity was assessed by ERG c-wave measurement. Results: KO of miR-204 resulted in the accumulation of neutral lipids in subretinal microglia. MiR-204 targeted the TGF-β receptor 2 gene in microglia. TGF-β markedly suppressed the expression of genes related to microglia lipid clearance. Eyes injected with RPE-derived EVs showed improved ERG c-wave responses compared to the fellow eyes injected with saline. Conclusions: This study supports that TGF-β/TGF-β receptor 2 regulates microglia lipid metabolism primarily by suppressing lipid clearance. By modulating TGF-β signaling, miR-204 in RPE-derived EVs likely enhances the lipid metabolic activities of subretinal microglia, which are crucial for the structural integrity and proper function of the outer retina and RPE. RPE-derived EVs and their delivery of miRNAs represent a potential therapeutic approach for treating retinal diseases, such as age-related macular degeneration, which involve dysregulated lipid metabolism in subretinal microglia.},
}
@article {pmid40961946,
year = {2025},
author = {Rao, RC and Arduini, BL and Borden, S and Sareen, D and Svendsen, C and Lee, P and Ryan, C and Kodati, S and Nyaiburi, C and Wolsieffer, K and Oh, E and Park, S and Ford, G and Dionne, K and Temple, S and Stern, J},
title = {Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes.},
journal = {Cell stem cell},
volume = {32},
number = {11},
pages = {1659-1670.e4},
pmid = {40961946},
issn = {1875-9777},
support = {U01 EY030581/EY/NEI NIH HHS/United States ; UG3 EY031810/EY/NEI NIH HHS/United States ; UH3 EY031810/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/transplantation/cytology ; Female ; Male ; Aged ; Treatment Outcome ; Middle Aged ; *Macular Degeneration/therapy ; *Stem Cell Transplantation/adverse effects/methods ; Visual Acuity ; *Geographic Atrophy/therapy ; *Stem Cells/cytology ; Aged, 80 and over ; },
abstract = {Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD.},
}
@article {pmid40961008,
year = {2025},
author = {Scupola, A and Hu, L and Cusato, M and Fossataro, C and Michieletto, M and Sammarco, MG and Rizzo, S and Savino, G},
title = {Brolucizumab for Wet Age-Related Macular Degeneration in Switch Patients: Long-Term Real-World Experience from a Tertiary Center.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1-11},
doi = {10.1159/000547471},
pmid = {40961008},
issn = {1423-0267},
abstract = {INTRODUCTION: This retrospective, single-center, observational cohort study evaluated the 3-year real-world efficacy and safety of intravitreal brolucizumab injections in patients with neovascular age-related macular degeneration (nAMD) who had previously been treated with other anti-vascular endothelial growth factor (VEGF) agents. A total of 97 eyes from 91 patients were included, all of whom completed 3 years of follow-up after switching to brolucizumab.<br><br>METHODS: Patients received intravitreal injections of 6 mg brolucizumab. Data on best-corrected visual acuity (BCVA), central subfield thickness (CST), intraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid (sRPEF), treatment intervals, and adverse events were collected over a 3-year follow-up period.<br><br>RESULTS: The mean age of patients was 78.9 &#xb1; 8.2 years, with a mean follow-up of 161.3 weeks. At 3-year follow-up, mean BCVA significantly improved, from 41.1 &#xb1; 6.5 at baseline to 50.7 &#xb1; 7.5 ETDRS letters (p < 0.001), and mean CST significantly decreased from 371.3 &#xb1; 136.7 to 299.1 &#xb1; 137.81 (p < 0.001). Significant reductions were observed in IRF (p < 0.001), SRF (p < 0.001), and sRPEF (p = 0.004). Mean injections per year were 4.7 &#xb1; 1.9, 3.9 &#xb1; 1.7, and 3.6 &#xb1; 1.9 in the first, second, and third years, respectively. Adverse events were noted in 4 patients after either the first or second injection, with no further events reported.<br><br>CONCLUSION: This study reports that brolucizumab provides favorable anatomical and functional outcomes and can reduce treatment burden in patients with nAMD due to its rapid and sustained efficacy and favorable safety profile.},
}
@article {pmid40960227,
year = {2025},
author = {Haj Najeeb, B and Gerendas, BS and Sacu, S and Leingang, O and Deak, G and Schmidt-Erfurth, U},
title = {Reshaping the Burden of nAMD: National, Regional, and Global Prevalence of MNV3 and Its Correlation With Life Expectancy-The RAP Study, Report 7.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {12},
pages = {37},
pmid = {40960227},
issn = {1552-5783},
mesh = {Humans ; *Life Expectancy/trends ; Prevalence ; Aged ; Male ; Female ; Global Health ; Aged, 80 and over ; *Wet Macular Degeneration/epidemiology/diagnosis ; Middle Aged ; },
abstract = {BACKGROUND: To report the global distribution of macular neovascularization type 3 (MNV3) and to redefine the associated burden of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A total of 4652 patients with treatment-na&#xef;ve nAMD were included. MNV3 was diagnosed using multimodal imaging methods. The prevalence of MNV3 in each country, region, continent and worldwide was calculated. The correlation between the prevalence of MNV3 and life expectancy in each country was estimated. Continent prevalence data was compared using a logistic (binomial) generalized linear mixed model (GLMM).<br><br>RESULTS: Our analysis revealed 4652 nAMD eyes from 47 countries, 575 (12.4%) of which had MNV3. In North America, the highest percentage was in Canada (17.6%), followed by the USA (11.5%). In Europe, the highest prevalence (23.4%) was in Austria and the lowest (4.3%) in Russia and Croatia. The prevalence in Asia, South America, and Australia was 6.6%, 9.4%, and 13.7%. A significant positive correlation was found between the MNV3 prevalence and life expectancy in 20 European countries (r = 0.63, P < 0.003). The GLMM revealed significantly lower odds for observing MNV3 in Asia compared to Europe (P < 0.01). No significant difference was observed in any other continent pair. The prevalence in Western Europe and Mediterranean region was higher than in Eastern Europe and the non-Mediterranean region (18.6% vs. 9.6%, P < 0.001; and 17.5% vs. 12.6%, P = 0.001, respectively).<br><br>CONCLUSIONS: MNV3 is more prevalent in Western and Mediterranean regions, likely because of higher life expectancy and a lower percentage of Asian ethnicity. AREDS supplements and the Mediterranean diet may not provide prophylactic benefits against the development of MNV3. The unique distribution pattern of MNV3 and its correlation with life expectancy should be considered in nAMD research to ensure adequate representation of MNV3 patients in clinical trials.},
}
@article {pmid40959859,
year = {2025},
author = {Emmert, R and McKenzie, T and Smith, D and Russell, H and Schultheis, G and Hartwell, M},
title = {Equity reporting in systematic reviews and meta-analysis for geographic atrophy: a PROGRESS-Plus assessment.},
journal = {Journal of osteopathic medicine},
volume = {},
number = {},
pages = {},
pmid = {40959859},
issn = {2702-3648},
abstract = {CONTEXT: As systematic reviews and meta-analyses (SRMAs) are crucial for treatment development, they must provide guidelines that represent diverse patient demographics to promote equitable health care. As new research and treatment modalities are being developed for geographic atrophy (GA), establishing an equitable research foundation is becoming vitally important to physicians as they personalize their treatment plans.<br><br>OBJECTIVES: This analysis aims to determine whether SRMAs pertaining to GA are reporting equity-related items utilizing the PROGRESS-Plus framework.<br><br>METHODS: We conducted a cross-sectional analysis by searching databases for systematic reviews and meta-analyses concerning GA from the year 2000 to November 2023. From this search, 176 articles returned, but only 57 of them met all the inclusion criteria. After screening the articles for inclusion, data pertaining to PROGRESS-Plus items were extracted. All analyses were conducted in a masked and duplicative fashion.&#xa0;&#x3c7; [2]&#xa0;tests were employed to determine whether associations existed between the variables.<br><br>RESULTS: From the initial search, 176 articles returned, of which 119 were excluded due to duplication, data unrelated to GA, or because it was animal-based research. Of the remaining 57 studies, 26 (45.6&#x202f;%) included zero PROGRESS-Plus items. Fewer articles from the US-reported equity items (31.3&#x202f;%, 5/16) compared to other countries (63.4&#x202f;%, 26/41), which held statistical significance (p=0.028).<br><br>CONCLUSIONS: The American Academy of Ophthalmology has created initiatives to increase diversity, equity, and inclusion within the subspecialty. By using the PROGRESS-Plus framework, this study concluded that the majority of the articles pertaining to GA do not meet equity item objectives. As these documents aid physicians in developing treatment plans, these findings are concerning as physicians may find it more difficult to individually tailor treatment plans according to each patient's holistic needs. Limitations in this study included unintentional omission or misclassification of research documents despite the comprehensive search string and double-blinded analysis. Furthermore, the results of this study cannot be generalized to other areas of research.},
}
@article {pmid40958430,
year = {2025},
author = {Fu, T and Ma, Y and Jiang, Y and Jiang, C and Li, X and Jiang, Q},
title = {Role of stem cells in ocular diseases: Progress and challenges.},
journal = {Journal of biomedical research},
volume = {},
number = {},
pages = {1-21},
doi = {10.7555/JBR.39.20250251},
pmid = {40958430},
issn = {1674-8301},
abstract = {Ocular diseases, including corneal disease, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity, can significantly impair vision and reduce the quality of life. Due to the fact that degenerated cells in these diseases are unable to regenerate, treatments for them have limited efficacy. Stem cell therapies are revolutionizing the treatment of degenerative eye conditions, enabling tissue and functional recovery through mechanisms such as cell replacement and paracrine signaling. This review examines the advancements in stem cell therapy for ocular diseases, from preclinical studies to early clinical trials, focusing on various types of stem cells, including embryonic stem cells, induced pluripotent stem cells (iPSCs), and mesenchymal stem cells. Significant progress has been made with iPSC-derived retinal pigment epithelium cell transplantation in AMD treatment, showing cell survival in trials as well as with mesenchymal stem cells for corneal repair through anti-inflammatory effects. Challenges remain, such as controlling differentiation to prevent tumorigenesis, managing immune rejection, and ensuring production that complies with Good Manufacturing Practice (GMP) standards. By integrating mechanistic insights with translational strategies, this review outlines pathways to optimize stem cell therapies for previously intractable ocular diseases.},
}
@article {pmid40958284,
year = {2025},
author = {Liu, J and Huang, Y and Dong, Z and Qian, C and Huang, B},
title = {Systematic review and sequential analysis of traditional Chinese medicine in the treatment of age-related macular degeneration based on GRADE evidence quality rating.},
journal = {Medicine},
volume = {104},
number = {37},
pages = {e44426},
pmid = {40958284},
issn = {1536-5964},
mesh = {Humans ; *Macular Degeneration/drug therapy/therapy ; *Medicine, Chinese Traditional/methods ; Randomized Controlled Trials as Topic ; *Drugs, Chinese Herbal/therapeutic use ; Treatment Outcome ; },
abstract = {BACKGROUND: This study systematically reviews the clinical efficacy and safety of traditional Chinese medicine (TCM) in the treatment of age-related macular degeneration (AMD), assesses the quality of evidence, and verifies the credibility of the research findings.<br><br>METHODS: Literature on TCM treatment for AMD was retrieved from PUBMED, Cochrane, Embase, China National Knowledge Infrastructure, SINOMED, Wanfang, and Technology Periodical Database (VIP) from inception to January 17, 2025. The selected literature was screened, data extracted, and evaluated. Meta-analysis was conducted using Review Manager 5.3, trial sequential analysis (TSA) using TSA v0.9 software, and grading of recommendations, assessment, development and evaluation evidence quality rating using.<br><br>RESULTS: A total of 52 randomized controlled trials were included. Meta-analysis results showed that the experimental group demonstrated better clinical efficacy compared with the control group (risk ratio [RR]&#x2005;=&#x2005;1.24, 95% confidence interval [CI]: 1.19-1.29, P&#x2005;<&#x2005;.00001), lower recurrence rates (RR&#x2005;=&#x2005;0.35, 95% CI: 0.21-0.57, P&#x2005;<&#x2005;.0001), and improvements in central macular thickness (weighted mean difference&#x2005;=&#x2005;0.79, 95% CI: -0.86 to -0.71, P&#x2005;<&#x2005;.00001) and best-corrected visual acuity (weighted mean difference&#x2005;=&#x2005;-0.76, 95% CI: -1.01 to -0.52), P&#x2005;<&#x2005;.00001). TSA further confirmed the efficacy of TCM in treating AMD. The grading of recommendations, assessment, development and evaluation evidence quality rating indicated that recurrence rates and best-corrected visual acuity (early treatment diabetic retinopathy study) were of very low-quality evidence, while other outcomes were of low-quality evidence.<br><br>CONCLUSION: TCM is safe and effective in the treatment of AMD, but additional high-quality clinical studies are necessary to further verify the results.},
}
@article {pmid40956390,
year = {2025},
author = {Yi, Z and Wen, C and Du, H and Wang, Y and Chen, S and Liu, J and Zhang, S and Wang, J and Xiao, X and Li, S and Jia, X and Jiang, Y and Ouyang, J and Wang, P and Hejtmancik, JF and Sun, W and Shen, H and Zhang, Q},
title = {Retinitis Pigmentosa-Associated Gene TRIM49 Regulates ULK1-Mediated Autophagy and Photoreceptor Phagocytosis by the Retinal Pigment Epithelium.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {43},
pages = {e12305},
pmid = {40956390},
issn = {2198-3844},
support = {202201011073//Science and Technology Planning Projects of Guangzhou/ ; SL2024A03J00525//Science and Technology Planning Projects of Guangzhou/ ; 82302095//National Natural Science Foundation of China/ ; 81970837//National Natural Science Foundation of China/ ; //Fundamental Research Funds of the State Key Laboratory of Ophthalmology/ ; 2021A1515110104//Basic and Applied Basic Research Foundation of Guangdong Province/ ; //GBRCE for Major Blinding Eye Diseases Prevention and Treatment/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Autophagy/genetics/physiology ; *Phagocytosis/genetics/physiology ; *Autophagy-Related Protein-1 Homolog/metabolism/genetics ; *Retinitis Pigmentosa/genetics/metabolism/pathology ; *Tripartite Motif Proteins/genetics/metabolism ; *Ubiquitin-Protein Ligases/genetics/metabolism ; Animals ; Intracellular Signaling Peptides and Proteins ; },
abstract = {Autophagy is pivotal for cellular homeostasis and photoreceptor outer segment (POS) phagocytosis by the retinal pigment epithelium (RPE) in retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa (RP). Yet, the mechanism of autophagy in the RPE remains largely unknown. RP is an inherited retinal degenerative condition, whose candidate genes provide avenues for dissecting novel autophagy factors. Here, whole exome sequencing of RP patients identified biallelic variants in TRIM49, a primate-specific gene involved in autophagy, as a novel cause of RP. Among human tissues TRIM49 is highly expressed in the RPE. In human RPE cells, deficiency of TRIM49 significantly disturbs cellular homeostasis and impairs the POS phagocytosis. Importantly, suppressed basal autophagy flux is present in TRIM49-depleted RPE cells, whereas enhanced autophagy flux is present in RPE cells overexpressing TRIM49. Variations of TRIM49 after treatment with multiple autophagy modulators indicate that TRIM49 is involved in the initiation of autophagy. TRIM49 interacts with the key regulator of autophagy initiation ULK1. Deficiency of TRIM49 down-regulates and overexpression of TRIM49 up-regulates ULK1 expression. Altogether, these findings identify TRIM49 as a critical regulator of ULK1-mediated autophagy and POS phagocytosis by the RPE, suggesting that RPE autophagy is a potential therapeutic target for retinal degenerative diseases.},
}
@article {pmid40956067,
year = {2025},
author = {Zuo, L and Ye, M and Chen, L and Xu, X and Huang, S and Li, X and Bai, W},
title = {Anthocyanin-Rich Berries and Their Bioactive Compounds in Ocular Health: Mechanisms and Therapeutic Potential.},
journal = {Journal of agricultural and food chemistry},
volume = {73},
number = {38},
pages = {23724-23741},
doi = {10.1021/acs.jafc.5c03411},
pmid = {40956067},
issn = {1520-5118},
mesh = {Humans ; *Anthocyanins/chemistry/administration &amp; dosage ; *Fruit/chemistry/metabolism ; Animals ; *Eye Diseases/metabolism/drug therapy/genetics ; *Plant Extracts/chemistry/administration &amp; dosage ; *Eye/metabolism/drug effects ; Antioxidants/chemistry ; Oxidative Stress/drug effects ; },
abstract = {As a global public health challenge, ocular diseases are driven by interconnected mechanisms, including oxidative stress, vascular abnormalities, and neurodegeneration. This review analyzes the multitarget mechanisms of berry-derived bioactive components (anthocyanins, proanthocyanidins, vitamin C, lutein, zeaxanthin, quercetin, and resveratrol) in regulating ocular homeostasis. Beyond antioxidant and anti-inflammatory effects, these compounds delay the progression of age-related macular degeneration, diabetic retinopathy, and glaucoma through mechanisms such as improving microcirculation, protecting photoreceptors, modulating angiogenesis, and inhibiting advanced glycation end-product deposition. Their protective effects involve the synergistic regulation of PI3K/AKT, Nrf2/HO-1, and VEGF pathways, supporting berry-based nutritional interventions for ocular health. Bioavailability and metabolism of these compounds are also discussed, highlighting their translational potential for the prevention and adjunctive therapy of ocular diseases.},
}
@article {pmid40955792,
year = {2025},
author = {Anderson, AJ and Ayton, LN and Robertson, EG and Nguyen, BN},
title = {Seeing a sunset: Exploring the joy of vision, in healthy eyes and ocular disease.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {},
number = {},
pages = {},
doi = {10.1111/opo.70019},
pmid = {40955792},
issn = {1475-1313},
support = {//Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne/ ; Stem Cell Therapies Mission grant APP2016039//Medical Research Future Fund/ ; Investigator Grant GNT#1195713//National Health and Medical Research Council/ ; //Victorian Optometrists Training and Education Trust/ ; },
abstract = {PURPOSE: Vision plays a critical role in the performance of various functional tasks, and can also be an inherent source of enjoyment unrelated to a functional task. This study aimed to explore the sources and importance of visual enjoyment and how these might alter with vision loss.<br><br>METHODS: Fourteen adults (26-81&#x2009;years) with self-reported healthy vision and 15 (37-84&#x2009;years) with vision loss (inherited retinal disease, glaucoma, age-related macular degeneration) participated. Across four focus groups (2&#x2009;&#xd7;&#x2009;healthy vision, 2&#x2009;&#xd7;&#x2009;vision loss), participants were asked about sources of visual enjoyment, attitudes around the distinction between vision to perform tasks versus vision as an inherent source of enjoyment, how sources of visual enjoyment may have changed through eye disease or aging, and experiences with eye care providers regarding visual enjoyment. Transcriptions were analysed using qualitative content analysis.<br><br>RESULTS: Almost all participants felt sources of visual enjoyment were important. Most could think of examples of visual enjoyment as distinct from visual function (e.g., appreciating leaf colour changes, stargazing), with a minority noting sources of enjoyment that either depended upon, or were facilitated by, good vision (e.g., playing golf, reading). Although around half believed the distinction between visual enjoyment and visual function was important, some were unclear whether there was a distinction or saw no distinction. Most felt that aging and vision loss with ocular disease had altered what they considered as sources of visual enjoyment. While direct experience of eye care practitioners considering personal sources of visual enjoyment when providing advice was mostly lacking, many respondents felt visual enjoyment would be important or beneficial to consider.<br><br>CONCLUSIONS: Sources of visual enjoyment are important to most people with and without vision loss. These results suggest that some patients may value having their personal sources of visual enjoyment considered by eye care providers.},
}
@article {pmid40955002,
year = {2025},
author = {Suh, YK and Lee, SH and Kim, MS},
title = {Outcomes of Re-Switching Anti-vascular Endothelial Growth Factor After Brolucizumab-Associated Inflammation in Age-related macular degeneration.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2025.0008},
pmid = {40955002},
issn = {2092-9382},
abstract = {PURPOSE: To investigate the anatomical and functional outcomes in cases of re-switching to previous anti-vascular endothelial growth factor (VEGF) agents due to intraocular inflammation (IOI) following a switch to brolucizumab in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This study included patients with nAMD who switched to brolucizumab and discontinued brolucizumab treatment due to IOI, with a follow-up duration of at least 6 months before and after brolucizumab treatment period. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and retinal fluid on optical coherence tomography were evaluated.<br><br>RESULTS: A total of 16 eyes from 16 patients were reviewed. 12.5% of patients achieved complete fluid resolution before brolucizumab treatment, which increased to 93.8% during brolucizumab therapy. However, after switching back to other anti-VEGF agents, the proportion of patients with dry macula decreased to 37.5%. There were no statistically significant changes in BCVA, CMT, or CCT throughout the study period.<br><br>CONCLUSIONS: In cases where brolucizumab treatment was discontinued due to IOI and switched back to other anti-VEGF agents, the anatomical response was insufficient, indicating the need for alternative treatment options.},
}
@article {pmid40954063,
year = {2025},
author = {Ma, Y and Hu, Y and Shi, X and Hu, X and Hong, W and Zhang, R},
title = {[ZHANG Ren's academic characteristics of acupuncture for refractory eye diseases in modern times with "homotherapy for heteropathy"].},
journal = {Zhongguo zhen jiu = Chinese acupuncture &amp; moxibustion},
volume = {45},
number = {9},
pages = {1311-1317},
doi = {10.13703/j.0255-2930.20240812-k0002},
pmid = {40954063},
issn = {0255-2930},
mesh = {*Acupuncture Therapy/history/methods ; Humans ; *Eye Diseases/therapy/history ; Acupuncture Points ; History, 20th Century ; China ; History, 21st Century ; },
abstract = {This paper introduces the academic characteristics of Professor ZHANG Ren in treatment with acupuncture for refractory eye diseases in modern times, guided by "homotherapy for heteropathy" (same therapy for different diseases sharing the same pathogenesis). The refractory eye diseases in modern times include a variety of conditions such as glaucoma, macular degeneration, diabetic retinopathy, high myopia and its complications, dry eye, cortical visual impairment and genetic eye diseases. The same therapy is used because these diseases share the similar location and pathogenesis. Professor ZHANG optimizes the methods of acupoint selection and provides the comprehensive prescriptions, "basic prescription, prescription based on disease differentiation, and supplementary prescription". A variety of acupuncture manipulation techniques are operated in clinical practice, such as compound needling methods, penetration needling, manipulations for promoting qi movement and conducting qi flow. "Early, regular and persistent" treatment is the common requirement with "the same acupoints, the same prescription and the same acupuncture method" as well as at "the same time". It is also proposed that the treatment should be provided flexibly according to the different symptoms, "identifying the differences within similarities".},
}
@article {pmid40952055,
year = {2025},
author = {Li, C and Zhou, L and Luo, T and Sun, H and Ma, R and Wang, J and Yang, MM},
title = {Integrative Multiomics Identifies CD64[+] Monocytes as Potential Contributors to Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {12},
pages = {32},
pmid = {40952055},
issn = {1552-5783},
mesh = {Animals ; Humans ; Mice ; *Monocytes/metabolism/immunology ; Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/genetics/metabolism/immunology ; Disease Models, Animal ; Flow Cytometry ; *Receptors, IgG/metabolism/genetics ; Genome-Wide Association Study ; Male ; Mice, Inbred C57BL ; Female ; Aged ; Choroid/metabolism ; Multiomics ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, characterized by chronic retinal inflammation and immune dysregulation. While myeloid cells have been increasingly implicated in AMD pathogenesis, the specific immune subsets responsible remain poorly defined. This study aimed to identify causal immune cell populations and elucidate their functional roles in AMD progression.<br><br>METHODS: We employed an integrative multiomics strategy encompassing Mendelian randomization (MR) analysis using genome-wide association study summary statistics, single-cell RNA sequencing (scRNA-seq) analysis of retinal pigment epithelium (RPE)/choroid tissues from patients with AMD and healthy controls (GSE230348), and flow cytometric (FCM) validation in a sodium iodate-induced dry AMD mouse model.<br><br>RESULTS: MR analysis identified a significant causal association between CD64 expression on CD14&#x207b;CD16&#x207b; monocytes and increased AMD risk (odds ratio, 1.179; P < 0.001). scRNA-seq profiling revealed a pronounced enrichment of CD14&#x207b;CD16&#x207b; monocytes in AMD tissues, with FCGR1A (CD64) expression specifically localized within this subset. Pseudotime trajectory analysis demonstrated dynamic activation and differentiation states among monocyte populations in AMD. Ligand-receptor interaction modeling identified three major signaling pathways, MIF-CD74-CXCR4, IGF1-IGF1R, and SEMA3C-PLXND1, mediating interactions between CD14&#x207b;CD16&#x207b; monocytes and RPE cells. FCM analysis of retinal single-cell suspensions in AMD mice confirmed a significantly higher proportion of CD64&#x207a; myeloid cells compared to controls.<br><br>CONCLUSIONS: This study identifies CD64&#x207a;CD14&#x207b;CD16&#x207b; monocytes as potential contributors to AMD and reveals their putative immunomodulatory crosstalk with RPE cells. These findings highlight CD64 as a promising biomarker and therapeutic target for mitigating myeloid-driven inflammation in AMD.},
}
@article {pmid40951367,
year = {2025},
author = {He, X and Li, C and Wang, Y and Du, Z and Jiang, J and Zhang, W and Peng, J and Peng, Z and Huang, T and Li, H and Kuang, Y and Yu, H and Liu, L and Yang, X},
title = {Association of Age-Related Eye Diseases with Comorbidity of Coronary Heart Disease and Depression in a Population-Based Cohort Study.},
journal = {Psychology research and behavior management},
volume = {18},
number = {},
pages = {1931-1942},
pmid = {40951367},
issn = {1179-1578},
abstract = {BACKGROUND: Coronary heart disease (CHD) and depression are highly comorbid and increase mortality risk. Although age-related eye diseases (AREDs) are independently associated with CHD and depression, their link to comorbidity remains unknown. Therefore, we aim to investigate the association between AREDs and the comorbidity of CHD and depression.<br><br>METHODS: Using UK Biobank data, we conducted a prospective cohort analysis with baseline assessments from March 2006 to December 2010 and follow-up until July 2021. AREDs include age-related macular degeneration, glaucoma, cataract, and diabetes-related eye diseases (DRED). Incident cases were identified via self-reports and hospital records. Multivariable Cox proportional hazard regression models were applied to investigate the association between AREDs and comorbidity risk.<br><br>RESULTS: Among 116,501 participants free of CHD and depression at baseline, 7,750 (6.65%), 3,682 (3.16%), and 741 (0.64%) developed CHD, depression, and their comorbidity over a mean of 11.82 years (inter-quartile range: 11.51-13.11) of follow-up. After adjusting for confounders, individuals with AREDs had a higher risk of developing CHD (hazard ratio [HR] 1.10, 95% confidence interval [CI]: 1.03-1.17), depression (HR 1.28, 95% CI: 1.16-1.42), and comorbidity (HR 1.37, 95% CI: 1.12-1.67). Compared to those without AREDs, individuals with cataract were associated with increased risks of comorbidity (HR 1.57, 95% CI: 1.23-2.03) and depression (HR 1.26, 95% CI: 1.10-1.43), while those with DRED had an increased risk of incident CHD (HR 1.33, 95% CI: 1.13-1.56).<br><br>CONCLUSION: The study found that individuals with AREDs had a higher risk of comorbid CHD and depression than of either condition independently. Our findings highlighted the importance of screening for the comorbidity of CHD and depression in the longitudinal management of AREDs.},
}
@article {pmid40951075,
year = {2025},
author = {Solano Pineda, DL and Marín Hernández, I and Gómez Morales, L and Nuñez Cruz, A and Flores Peredo, V and González Rubio Medina, E and Medina Quero, K and Vargas Hernández, MA and Escalera Arroyo, P},
title = {Real-World Outcomes of Antiangiogenic Therapy in Patients With Wet Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e89937},
pmid = {40951075},
issn = {2168-8184},
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in developing countries. The treatment of choice is intravitreal antiangiogenic therapy. However, there are discrepancies between outcomes observed in real-world clinical practice and those reported in clinical trials such as RIVAL, MARINA, ANCHOR, and PrONTO. Objective: The objective of this study was to explore real-world outcomes in visual acuity (VA) and central macular thickness (CMT) in patients with wet AMD treated with antiangiogenic therapy. Methods: This was an ambispective, observational, and analytical study. A total of 110 patients (132 eyes) diagnosed with wet AMD were included. All had complete clinical records, optical coherence tomography reports, and VA data from January 2017 to June 2020. Results: More than 80% of the eyes showed improvement in VA post-loading dose, along with a statistically significant reduction in CMT. The number of antiangiogenic injections ranged from 3 to 33, with an average follow-up of 20.8±12.5 months. Conclusion: Treatment received in real-world clinical practice differs from the protocols established in multicenter trials, particularly regarding injection frequency. Despite these variations, a positive trend was observed in both visual improvement and CMT reduction at the end of follow-up.},
}
@article {pmid40950238,
year = {2025},
author = {Lu, YR and Cameron, JC and Hu, Y and Shen, H and Shirahama, S and Tyshkovskiy, A and Chen, Z and Ai, J and Zhu, DY and Karg, MM and Chew, LA and Bell, GW and Jena, SG and He, Y and Seifert, P and Shu, DY and Ei-Brolosy, MA and Lou, Q and Zhang, B and Puszynska, AM and Qiu, X and Tian, X and Gregory-Ksander, M and Gladyshev, VN and Sinclair, DA and Saint-Geniez, M and Buenrostro, JD and Rickman, CB and Ksander, BR and Weissman, JS},
title = {Reprogramming Factors Activate a Non-Canonical Oxidative Resilience Pathway That Can Rejuvenate RPEs and Restore Vision.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.08.30.673239},
pmid = {40950238},
issn = {2692-8205},
abstract = {UNLABELLED: Oct4, Sox2, and Klf4 (OSK) Yamanaka factors induce pluripotency and reverse age-related epigenetic changes, yet the mechanisms by which they promote rejuvenation remain poorly explored. Oxidative stress contributes to CNS aging and retinal pigmented epithelium (RPE) degeneration in age-related macular degeneration. We find that OSK expression in RPE restores retinal structure and visual function in aged mice and promotes oxidative resilience through a non-canonical, Tet2-independent pathway. Integrative functional genomics identifies GSTA4, a detoxifying enzyme that clears the lipid peroxidation byproduct 4-HNE, as a necessary and sufficient OSK effector. Dynamic GSTA4 regulation by OSK recapitulates a stem cell derived stress resilience program. GSTA4 overexpression alone enhances mitochondrial resilience, rejuvenates the aged RPE transcriptome, and reverses visual decline. GSTA4 is consistently upregulated across diverse lifespan-extending interventions suggesting a broader pro-longevity role. These findings uncover a previously unrecognized protective axis driven by Yamanaka factors that circumvents reprogramming, providing therapeutic insights for age-related diseases.<br><br>HIGHLIGHTS: OSK-GSTA4 provides a dynamic, Tet2-independent stress-resilience axis.Functional genomics pinpoints GSTA4 as a direct downstream effector activated by OSK.RPE aging involves progressive accumulation of 4-HNE that can be detoxified by GSTA4.Enhancing GSTA4 rejuvenates RPE cells, restores vision and is associated with lifespan-extending interventions.},
}
@article {pmid40949825,
year = {2025},
author = {Paudel, N and Moran, EM and Stafford, S and McVicker, K and Stratieva, P and Daly, A},
title = {Prioritising the Burden of Geographic Atrophy and Treatment Expectations: A Modified Nominal Group Technique Study with International Patient-Led Organisations.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3317-3329},
pmid = {40949825},
issn = {1177-5467},
abstract = {AIM: Geographic atrophy (GA), an advanced form of dry AMD, impacts over 5 million people globally and leads to progressive, irreversible vision loss. Current approaches to GA treatment aim to prevent and delay disease progression and preserve remaining vision. However, there is a debate on what constitutes a meaningful treatment outcome for patients. The aim of this study was to prioritise challenges associated with GA and desired treatment expectations from therapies using a modified Nominal Group Technique (NGT).<br><br>METHODS AND ANALYSIS: The study employed a modified nominal group technique (NGT), a widely used, validated, structured, facilitated group meeting to generate consensus. Representatives from patient-driven international research funding and support organizations were invited to participate. Two questions, one asking the impact of GA on patients and caregivers and another asking the treatment expectations of GA therapies were posed during the NGT session. Standard NGT methods were followed to generate top 10 challenges of living with GA and treatment expectation as perceived by the participants.<br><br>RESULTS: The group ranked loss of independence (score - 32/50), difficulty recognizing faces (score - 28/50), impairment in daily living activities (scores - 11 to 22/50), and mental health issues (scores - 19/50 - anxiety, 21/50 - depression) as the most significant challenges faced by people living with GA. The group also prioritised stability of vision (score - 47/50), ability to recognise faces (score - 27/50) and one time therapy (score - 19/50) as their top expectations from GA treatments.<br><br>CONCLUSION: This study successfully used the NGT to prioritise challenges associated with GA and treatment expectation of GA therapies. The consensus results imply that meaningful progress in GA care will come from therapies that realistically aim to slow further vision loss, are convenient to use, and are delivered alongside psychosocial and low-vision support.},
}
@article {pmid40948984,
year = {2025},
author = {Oh, E and Jun, JH and Choi, JY and Yoo, TK},
title = {Systemic inflammation at the oral-ocular interface: a 3P medicine perspective on the relationship between periodontitis and eye diseases.},
journal = {The EPMA journal},
volume = {16},
number = {3},
pages = {571-587},
pmid = {40948984},
issn = {1878-5077},
abstract = {RATIONALE AND PURPOSE: Periodontitis is a common source of chronic systemic inflammation, driven by bacterial translocation and cytokine release through ulcerated gingival epithelium, and may contribute to the development of various chronic ocular diseases. This study investigated the association between periodontitis and multiple ocular conditions, interpreting the findings within the framework of Predictive, Preventive, and Personalized Medicine (3PM).<br><br>We hypothesized that periodontitis, as a treatable inflammatory condition, serves as a predictive marker and modifiable risk factor for ocular diseases involving vascular and immune-mediated mechanisms. Data from 11,448 adults aged&#x2009;&#x2265;&#x2009;40&#xa0;years from the Korea National Health and Nutrition Examination Survey (2008-2010) were analyzed. Periodontal status was classified using the Community Periodontal Index (CPI): no periodontitis (CPI&#x2009;&#x2264;&#x2009;2), moderate (CPI&#x2009;=&#x2009;3), and severe (CPI&#x2009;=&#x2009;4). Ophthalmologists assessed ocular diseases, including cataract, pterygium, diabetic retinopathy, glaucoma suspect, blepharoptosis, and age-related macular degeneration (AMD), using standardized diagnostic protocols. Multivariable logistic regression adjusted for key covariates, and Pearson correlation analysis was conducted.<br><br>RESULTS: Periodontitis was independently associated with higher risks of cataract (adjusted OR&#x2009;=&#x2009;1.26), diabetic retinopathy (OR&#x2009;=&#x2009;1.66), pterygium (OR&#x2009;=&#x2009;1.22), glaucoma suspect (OR&#x2009;=&#x2009;1.10), and blepharoptosis (OR&#x2009;=&#x2009;1.16). These associations were more pronounced in individuals with severe periodontitis. No significant association was observed with early or late AMD. CPI scores showed weak but significant positive correlations with several ocular conditions, particularly cataract and diabetic retinopathy.<br><br>Periodontitis may serve as a predictive biomarker for ocular diseases with shared inflammatory and vascular pathways. Early identification and management of periodontal disease offer a targeted preventive strategy to reduce systemic inflammatory burden and ocular comorbidities. Personalized care models incorporating periodontal status into ocular screening protocols may improve diagnostic precision and enable risk-adapted interventions. These findings support the integration of oral health into multidisciplinary care frameworks, advancing the paradigm shift from reactive to predictive and personalized ophthalmology.},
}
@article {pmid40948806,
year = {2025},
author = {Bochnička, J and Kremláček, J},
title = {Use of functional magnetic resonance imaging in the evaluation of neural plasticity in macular degeneration.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1622244},
pmid = {40948806},
issn = {1662-4548},
abstract = {This review evaluates the use of functional Magnetic Resonance Imaging (fMRI) to investigate brain plasticity in Age-Related Macular Degeneration (AMD). An analysis of studies utilizing fMRI methods identified three primary research approaches: task-based fMRI (17 studies), resting-state fMRI (4 studies), and population receptive fields (pRF) with population connective fields modeling (pCF; 3 studies). The review outlines the principles behind each fMRI methodology and summarizes the key functional and morphological findings. Results consistently demonstrated significant structural and connectivity reorganization in the brains of individuals with AMD, suggesting that the brain undergoes adaptive responses to sensory loss. Voxel-based morphometric findings, measuring the gray matter volume loss in visual cortex, further confirm these structural changes, which appear to correlate with altered functional connectivity. These insights underscore the intricate relationship between sensory deficits and cognitive function in AMD and emphasize the potential for targeted therapeutic interventions. FMRI emerges as a vital tool in group studies for understanding the neural underpinnings of AMD and its broader cognitive implications.},
}
@article {pmid40947728,
year = {2025},
author = {Thomas, JO and Idowu, IM},
title = {Phytochemicals in Ginkgo biloba for Age-Related Eye Disease - A Review.},
journal = {Journal of dietary supplements},
volume = {22},
number = {6},
pages = {907-938},
doi = {10.1080/19390211.2025.2560365},
pmid = {40947728},
issn = {1939-022X},
mesh = {*Ginkgo biloba/chemistry ; Humans ; *Phytochemicals/pharmacology/therapeutic use ; *Plant Extracts/therapeutic use/pharmacology ; Antioxidants/pharmacology/therapeutic use ; Macular Degeneration/drug therapy ; *Eye Diseases/drug therapy ; *Phytotherapy ; Animals ; Diabetic Retinopathy/drug therapy ; Anti-Inflammatory Agents/pharmacology ; Glaucoma/drug therapy ; Oxidative Stress/drug effects ; Flavonoids/pharmacology ; Ginkgo Extract ; },
abstract = {Ginkgo biloba is a rich source of phytochemicals and antioxidants derived from plant extracts, and its therapeutic potential is increasingly recognized in ocular health. Eye diseases such as glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) are among the leading causes of vision impairment worldwide, with current therapies often failing to counteract oxidative stress and retinal neurodegeneration. Ginkgo biloba, a medicinal plant used for centuries in Traditional Chinese Medicine (TCM), contains diverse flavonoids and terpenoids with potent antioxidant, anti-inflammatory, and neuroprotective properties. However, the specific contributions of these phytochemicals to ocular protection and the optimization of delivery strategies for standardized plant extracts remain insufficiently explored. This review examines evidence on standardized Ginkgo biloba extracts (GBEs) for ocular health, highlighting their ability to reduce oxidative damage, regulate inflammation, and protect retinal cells in major eye diseases. We hypothesize that standardized GBEs, when formulated via advanced ocular drug delivery systems, could enhance retinal bioavailability and efficacy, serving as viable adjunct or alternative therapies for glaucoma, DR, and AMD. The objectives are to summarize current knowledge on the phytochemical composition of Ginkgo biloba and its mechanisms of ocular protection, critically evaluate preclinical and clinical evidence of its use in eye diseases, and explore novel formulation and delivery strategies to overcome the bioavailability challenges of these plant extracts.},
}
@article {pmid40947063,
year = {2025},
author = {Anderson, CA and Trefry, SV and Barrera, MD and Boghdeh, N and Sreepangi, S and Opoku, L and Galarza, MF and Bliss, AR and Bleach, JL and Alem, F and Ronzier, E and Cerchin, ES and Gardner, CL and Burke, CW and Narayanan, A},
title = {Verteporfin is a broad-spectrum inhibitor of arboviruses and influences viral and host-based events.},
journal = {Antiviral research},
volume = {243},
number = {},
pages = {106281},
doi = {10.1016/j.antiviral.2025.106281},
pmid = {40947063},
issn = {1872-9096},
mesh = {Animals ; *Verteporfin/pharmacology ; Humans ; *Antiviral Agents/pharmacology ; *Encephalitis Virus, Venezuelan Equine/drug effects ; Viral Load/drug effects ; Virus Replication/drug effects ; *Host-Pathogen Interactions/drug effects ; *Arboviruses/drug effects ; Cell Line ; *Arbovirus Infections/drug therapy/virology ; Disease Models, Animal ; },
abstract = {There is an unmet need for broadly effective therapeutic strategies to address the globally expanding health burden caused by vector-transmitted viruses. Protein-protein interactions involving host and viral proteins are key regulators of a productive viral infection and interruption of such interactions can exert broad-spectrum antiviral outcomes. Verteporfin (VP), a small molecule that is currently approved by the United States Food and Drug Administration (FDA) for the treatment of age-related macular degeneration and a known Yes-associated protein (YAP) inhibitor, was identified as a robust inhibitor of Venezuelan Equine Encephalitis Virus (VEEV) TC-83 strain from a protein-protein interaction inhibitor library. VP demonstrated a cell type independent reduction of viral load with inhibitory mechanism including reduction of nonstructural and structural protein levels. VP treatment also impacted its known target YAP, resulting in reduced expression of total and phosphorylated YAP in virus-infected cells. The in vivo assessment of VP in a lethal infection rodent model demonstrated early promise by increasing survival of infected animals, while also indicating the need for additional improvements in dosing strategy. Assessment of VP-mediated inhibition of other RNA viruses including Old- and New-world alphaviruses, a prototype flavivirus and bunyavirus demonstrated the potential of VP to function as a broad-spectrum inhibitor of vector-transmitted viruses.},
}
@article {pmid40944941,
year = {2025},
author = {Chirpaz, N and Matagrin, B and Gauthier, L and Elbany, S and Rocher, A and Mathis, T and Fenniri, I and Denis, P and Kodjikian, L and Burillon, C and Dot, C},
title = {Comparative Analysis of Long-Term Outcomes of Submacular Hemorrhage in AMD: A Real-Life Study.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1-8},
doi = {10.1159/000548392},
pmid = {40944941},
issn = {1423-0267},
abstract = {INTRODUCTION: Submacular hemorrhage (SMH) is a severe complication of neovascular age-related macular degeneration (nAMD), often causing profound vision loss. The aim of this study was to assess the long-term outcomes of SMH patients managed with anti-VEGF monotherapy (MT) versus surgical displacement (SD) and to identify prognostic factors for visual acuity.<br><br>METHODS: This multicenter retrospective study included patients with SMH secondary to nAMD treated in three hospitals in Lyon between 2018 and 2023. Patients were treated with MT or underwent pneumatic displacement (PD) or SD. The best-corrected visual acuity (BCVA) and clinical parameters were assessed at baseline (time of SMH onset), months 1, 3, 9, and 12.<br><br>RESULTS: Sixty-six eyes were included: 33 received MT, 6 underwent PD, and 27 underwent SD. The baseline VA was strongly reduced (mean BCVA: 0.14). The VA improved to 0.21 at M1, 0.29 at M3, and 0.33 at M6 but was stabilized at 0.28 at M12. At M12, VA did not significantly differ between MT and SD groups (0.27 vs. 0.32, p = 0.624). However, multivariate analysis revealed a significantly greater VA gain in the SD group (p = 0.025), despite more severe baseline characteristics. SMH thickness was significantly associated with a poorer VA (p = 0.02).<br><br>CONCLUSION: SD may offer greater visual improvement in cases of large and thick SMH. Maximum SMH thickness appears to be a key prognostic factor. Treatment decisions should consider initial hemorrhage severity.},
}
@article {pmid40943788,
year = {2025},
author = {Parravano, M and Fragiotta, S and Polito, MS and Varano, M and Querzoli, G and Rossi, T},
title = {Retinal Vessel Coronal Displacement in Intermediate Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
pmid = {40943788},
issn = {2077-0383},
support = {NA//Italian Ministry of Health/ ; NA//Fondazione Roma/ ; },
abstract = {Introduction: This pilot study aimed to test the feasibility of a novel vectorial image analysis method to quantify coronal microvascular displacement in different retinal plexuses in intermediate age-related macular degeneration (iAMD) over 6 months. Material and methods: A retrospective series of iAMD patients with at least 6-month follow-up was included if they had complete medical records, best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and OCT angiography (OCTA). En-face (coronal) vascular displacement between baseline and 6 months was assessed in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using the Farneback motion tracking algorithm applied to consecutive OCTA scans. Results: Eighteen eyes of 18 iAMD patients met the inclusion criteria. Average coronal vascular displacement (T0-T6) was 13.7 ± 7.72 µm for the SCP, 15.11 ± 10.06 µm for the DCP, and 19.02 ± 12.25 µm for the CC slab. Reticular pseudodrusen (RPD) was associated with greater displacement in the DCP (p = 0.047), but not in the SCP (p = 0.980) or CC (p = 0.473). Quantitative analysis confirmed the highest DCP displacement in RPD eyes (66.7%, p = 0.02), while drusenoid pigment epithelial detachment showed the greatest reorganization in the CC (100%, p = 0.02). Discussion: Retinal vessels undergo significant tangential displacement in iAMD, suggesting a structural reorganization of the microvasculature. Such remodeling may constitute a compensatory response to ultrastructural alterations resulting in ischemia.},
}
@article {pmid40943713,
year = {2025},
author = {Dorronzoro-Ramirez, E and Sanchez-Tena, MA and Alvarez-Peregrina, C and Cardenas Rebollo, JM and Flores Cervantes, D and Sánchez-Ramos, C},
title = {Visual Outcomes of a Non-Diffractive Extended Depth-of-Focus Intraocular Lens in Patients with Early-Stage Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {17},
pages = {},
pmid = {40943713},
issn = {2077-0383},
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in older adults and often coexists with cataracts. The indication of presbyopia-correcting intraocular lenses (IOLs) in these patients remains controversial. This study aimed to evaluate the clinical performance of a non-diffractive extended depth-of-focus (EDOF) IOL (LuxSmart™) compared to a monofocal plus IOL (Tecnis Eyhance™) in cataract patients with early-stage dry AMD. Methods: In this prospective observational study, 41 patients with early-stage AMD underwent bilateral cataract surgery with either LuxSmart™ or Tecnis Eyhance™ IOL implantation, targeting postoperative emmetropia. The eye selected for analysis was the first eye scheduled for surgery. Preoperative and postoperative evaluations included high and low-contrast distance visual acuity, intermediate and near visual acuity, defocus curves, ocular light scatter (halometry), and quality of life assessment (NEI VFQ-25). Postoperative biometric accuracy and refractive outcomes were also analyzed. Results: Both IOLs showed high refractive accuracy, with 100% of eyes within ±0.50 D of target. Postoperative uncorrected distance visual acuity was 0.10 ± 0.06 LogMAR for Eyhance and 0.07 ± 0.02 for LuxSmart (p = 0.06). Low contrast VA at 20% was 0.22 ± 0.11 (Eyhance) and 0.26 ± 0.16 (LuxSmart) (p = 0.49). Depth of focus was approximately 1.75 D for both lenses. Light scatter (LDI) improved postoperatively in both groups with no significant differences (p = 0.54). VFQ-25 scores showed improvement in daily activities, though no changes were observed in driving or mental health domains. Conclusions: Both lenses are safe and effective options for early AMD patients undergoing cataract surgery, providing good functional vision at multiple distances.},
}
@article {pmid40943535,
year = {2025},
author = {Alibrandi, S and Mordà, D and Scimone, C and D'ascola, A and Aliquò, F and Pozzato, A and Scalinci, SZ and D'Angelo, R and Sidoti, A and Donato, L},
title = {QMR[®] and Patient Blood-Derived Secretome Modulate RPE microRNA Networks Under Oxidative Stress.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943535},
issn = {1422-0067},
mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Oxidative Stress/drug effects ; *Secretome/metabolism ; Cell Line ; *Gene Regulatory Networks ; Apoptosis ; Gene Expression Regulation ; },
abstract = {Oxidative stress destabilizes microRNA homeostasis in the retinal pigment epithelium (RPE), driving apoptosis and the epithelial-to-mesenchymal transition, which contribute to age-related macular degeneration. We investigated whether Quantum Molecular Resonance (QMR[®]) electrostimulation, alone or combined with Patient Blood-Derived (PBD) secretoma, can reprogram the RPE miRNome and mitigate stress-induced damage. Human ARPE-19 cells were exposed to tert-butyl-hydroperoxide and treated with QMR[®], PBD secretome, or their combination. The deep sequencing of small RNAs at 24 h and 72 h, followed by differential expression and pathway enrichment analyses, delineated treatment-driven miRNA signatures. Oxidative stress deregulated > 50 miRNAs, enriching pro-apoptotic, fibrotic, and inflammatory pathways. QMR[®] restored roughly 40% of these miRNAs and upregulated additional cytoprotective species such as miR-590-3p, a known regulator of the NF-κB and NLRP3 pathways according to validated target databases. While these observations suggest the potential involvement of inflammatory and stress-related cascades, functional assays will be required to directly confirm such effects. Secretome treatment preferentially increased anti-inflammatory miR-146a-5p and regenerative miR-204-5p while suppressing pro-fibrotic let-7f-5p. Combined QMR[®] + secretome triggered the broadest miRNA response, normalizing over two-thirds of stress-altered miRNAs. These changes are predicted to influence antioxidant, anti-apoptotic, and anti-fibrotic pathways, although they did not translate into additional short-term cytoprotection compared with QMR[®] alone. These data indicate that QMR[®] and PBD secretome modulate complementary miRNA programs that converge on stress response networks. This broader molecular reprogramming may reflect regulatory complementarity, but functional validation is needed to determine whether it provides benefits beyond those observed with QMR[®] alone. These findings offer molecular insights into potential non-invasive, cell-free strategies for retinal degeneration, although in vivo validation will be required before any clinical translation to Age-Related Macular Degeneration (AMD) therapy.},
}
@article {pmid40943481,
year = {2025},
author = {Di Gregorio, J and Zerti, D and Carozza, G and Capozzo, A and Flati, V and Feligioni, M and Maccarone, R},
title = {Hormetic Effects of Curcumin in RPE Cells: SIRT1 and Caspase-3 Inactivation with Implications for AMD.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943481},
issn = {1422-0067},
support = {07_progetto_ricerca_ateneo_zerti//intramural funding University of L'Aquila/ ; 07_DG_2025_12//Intramural funding Department of Biotechnological and Applied Clinical Sciences/ ; },
mesh = {*Curcumin/pharmacology ; Humans ; *Sirtuin 1/metabolism ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; *Caspase 3/metabolism ; *Macular Degeneration/metabolism/drug therapy/pathology ; Oxidative Stress/drug effects ; *Hormesis ; Cell Line ; Apoptosis/drug effects ; },
abstract = {Retinal Pigment Epithelium (RPE), a component of the blood-retinal barrier, plays a pivotal role in maintaining retinal homeostasis and visual function. Dysfunction of the RPE is an early event that triggers photoreceptor death, in Age-related Macular Degeneration (AMD), a multifactorial disorder primarily caused by an imbalance between endogenous antioxidant defenses and reactive oxygen species production. Our in vitro study investigated the hormetic effects of curcumin in human RPE cells (ARPE-19), focusing on its capability to modulate two enzymes related to the onset of AMD: Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase enzyme involved in cellular metabolism, aging, and stress response, and caspase-3, a crucial enzyme in programmed cell death. Curcumin exhibited classic hormetic doseresponses, with low concentrations (5-10 μM) providing cytoprotection while at high doses (≥20 μM) inducing toxicity. Under moderate oxidative stress, acetylated p53 was significantly reduced, indicating SIRT1 activation; curcumin 10 μM restored basal SIRT1 activity, while 5 µM did not. Both concentrations significantly decreased cleaved caspase-3 levels, demonstrating the anti-apoptotic effects of curcumin. Our results reveal curcumin's hormetic mechanisms of RPE protection and emphasize the critical importance of dose optimization within the hormetic window for AMD therapeutic development.},
}
@article {pmid40943417,
year = {2025},
author = {Kłodnicka, K and Januszewski, J and Tyc, H and Michalska, A and Forma, A and Teresińska, B and Rejdak, R and Baj, J and Dolar-Szczasny, J},
title = {From Pathophysiology to Innovative Therapies in Eye Diseases: A Brief Overview.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943417},
issn = {1422-0067},
mesh = {Humans ; *Eye Diseases/therapy/physiopathology/diagnostic imaging ; Tomography, Optical Coherence ; Animals ; Genetic Therapy/methods ; Precision Medicine ; Macular Degeneration/therapy ; Molecular Imaging/methods ; },
abstract = {Molecular imaging and precision therapies are transforming ophthalmology, enabling earlier and more accurate diagnosis and targeted treatment of sight-threatening diseases. This review focuses on age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis, examining high-resolution imaging techniques such as optical coherence tomography (OCT), OCT angiography, MALDI-MSI, and spatial transcriptomics. Artificial intelligence supports these methods by improving image interpretation and enabling personalized analysis. The review also discusses therapeutic advances, including gene therapies (e.g., AAV-mediated RPE65 delivery), stem cell-based regenerative approaches, and biologics targeting inflammatory and neovascular processes. Targeted molecular therapies targeting specific signaling pathways, such as MAPK, are also explored. The combination of single-cell transcriptomics, proteomics, and machine learning facilitates the development of personalized treatment strategies. Although these technologies hold enormous potential, their implementation in routine clinical care requires further validation, regulatory approval, and long-term safety assessment. This review highlights the potential and challenges of integrating molecular imaging and advanced therapies in the future of precision ophthalmic medicine.},
}
@article {pmid40943357,
year = {2025},
author = {Dörschmann, P and Prinz, M and Schmitkall, G and Roider, J and Klettner, A},
title = {Specific Assay Protocols for Porcine Single-Eye Retinal Pigment Epithelium Concerning Oxidative Stress and Inflammation.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943357},
issn = {1422-0067},
support = {03LW0148//German Federal Ministry of Education and Research/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology/drug effects/cytology ; Animals ; *Oxidative Stress/drug effects ; Swine ; *Inflammation/metabolism/pathology ; Cell Survival/drug effects ; Macular Degeneration/metabolism/pathology ; Cells, Cultured ; Cytokines/metabolism ; Lipopolysaccharides/pharmacology ; Poly I-C/pharmacology ; Tumor Necrosis Factor-alpha ; },
abstract = {The retinal pigment epithelium (RPE) is strongly involved in the pathogenesis of several retinal diseases, such as age-related macular degeneration (AMD). RPE models addressing specific pathological pathways are of high importance for understanding cellular pathomechanisms and pre-clinical screening of potential new therapeutics. The goal of this study is to establish standard operation protocols for single-eye porcine RPE preparation for AMD-relevant models of oxidative stress (RPE-Ox) and inflammation (RPE-Inf). Porcine primary RPE were prepared from one eye and seeded into one well of 12-well plates or, for polar differentiation, in transwell inserts. Different coatings (Poly-ᴅ-Lysine and laminin) and serum content of media (10%, 5%, and 1%) were tested to determine optimal culture parameters. For RPE-Ox, cells were treated with NaIO3, CoCl2, or erastin; cell viability (thiazolyl blue tetrazolium bromide, MTT), and gene expression (RT-qPCR) were determined. For RPE-Inf, cells were treated with lipopolysaccharide (LPS), polyinosinic/polycytidylic acid (Poly I:C), or tumor necrosis factor alpha (TNF-α); cell viability (MTT), cytokine secretion (ELISA), and gene expression (RT-qPCR) were determined. For transwell plates in RPE-Inf, cell viability (MTT), polar cytokine secretion (ELISA), gene expression (RT-qPCR), and transepithelial electrical resistance (TEER) for barrier assessment were conducted. For RPE-Ox, effective LD50 could be achieved by using 24 h stimulation with 25 µm erastin, seven days after preparation in 5% serum cultures, without coating. For gene expression assessment, the use of Poly-ᴅ-Lysine is recommended. For RPE-Inf, three days of LPS stimulation (1 µg/mL) showed effective cytokine activation with 5% serum on uncoated 12-well plates. Transwell plates are not recommended for cytokine secretion assessment. It can be used for cell barrier assays in which LPS also showed effective cell barrier decrease and gene expression assays. Two specific best practice protocols for the use of porcine single-eye cultures in AMD research concerning oxidative stress and inflammation with optimized parameters were established and are provided.},
}
@article {pmid40943078,
year = {2025},
author = {York, LR and Ma, H and Le, Y and Griffin, CT and Ding, XQ},
title = {RIPK3 Contributes to Thyroid Hormone-Induced Photoreceptor Degeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {17},
pages = {},
pmid = {40943078},
issn = {1422-0067},
support = {R01 EY033841/EY/NEI NIH HHS/United States ; R01EY033841, P30EY021725, P30GM122744, and R35HL144605/GF/NIH HHS/United States ; R35 HL144605/HL/NHLBI NIH HHS/United States ; P30 GM122744/GM/NIGMS NIH HHS/United States ; P30 EY021725/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism/genetics ; Mice ; Mice, Knockout ; *Retinal Degeneration/metabolism/pathology/genetics/chemically induced ; *Thyroid Hormones/metabolism ; Mice, Inbred C57BL ; Necroptosis ; *Photoreceptor Cells, Vertebrate/metabolism/pathology ; Protein Kinases/metabolism/genetics ; *Triiodothyronine ; },
abstract = {Thyroid hormone (TH) regulates cell proliferation, differentiation, and metabolism. Increased TH levels in circulation are associated with a higher incidence of age-related macular degeneration. In mice, TH treatment causes photoreceptor degeneration, which is accompanied by an increase in receptor-interacting serine/threonine-protein kinase 3 (RIPK3) in the retina. Here, we investigated the contribution of RIPK3/necroptosis to TH-induced photoreceptor degeneration using mice deficient in RIPK3 and the necroptotic mixed lineage kinase domain-like protein (MLKL). Wild-type (C57BL/6) and mutant mice at postnatal day 30 received triiodothyronine (T3, 20 µg/mL in drinking water) for four weeks, followed by the evaluation of photoreceptor survival/death and retinal function. Deletion of Ripk3 preserved photoreceptor integrity against T3-induced degeneration, evidenced by improved retinal morphology, increased cone density, improved retinal light responses, and reduced cell death. This protection was observed in both global and photoreceptor-specific Ripk3 knockout mice. In contrast, the deletion of Mlkl did not protect photoreceptors. This work supports the view that RIPK3, but not MLKL, contributes to TH-induced photoreceptor degeneration. The lack of protection from Mlkl deletion suggests that RIPK3's action is likely mediated via a necrosome-independent mechanism. These findings provide significant insight into how TH signaling induces photoreceptor degeneration and implicate RIPK3 as a potential therapeutic target.},
}
@article {pmid40942117,
year = {2025},
author = {Starvaggi, J and Di Chio, C and De Luca, F and Previti, S and Zappalà, M and Ettari, R},
title = {The Role of Nutraceuticals in Age-Related Ocular Diseases.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {17},
pages = {},
pmid = {40942117},
issn = {1420-3049},
mesh = {Humans ; *Dietary Supplements ; *Eye Diseases/drug therapy ; Antioxidants/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy ; Animals ; Cataract/drug therapy ; Anti-Inflammatory Agents/therapeutic use/pharmacology ; Neuroprotective Agents/therapeutic use/pharmacology ; },
abstract = {Although conventional medicine has seen substantial progress in recent years, there is a growing interest in nutraceuticals, bioactive compounds derived from natural sources such as plants, fruits, and cereals, due to their potential therapeutic applications. These substances have garnered increasing attention for their capacity to support ocular health and to aid in the prevention and management of age-related eye disorders, including age-related macular degeneration (AMD), cataracts, and glaucoma. This review provides a comprehensive and detailed analysis of selected nutraceuticals related to ocular health and diseases. It aims to define their pharmacodynamic properties, to elucidate the molecular and cellular mechanisms underlying their effects and to critically evaluate the current evidence regarding their potential clinical applications. By integrating findings from both preclinical and clinical studies, this review seeks to offer insights into the role of these nutraceuticals in the prevention, management, and adjunctive treatment of various ocular disorders, thereby suggesting future research directions and clinical practice. Notable attention is given to their antioxidant, anti-inflammatory, and neuroprotective properties, which are believed to contribute to the preservation of visual function and the deceleration of disease progression. Elucidating the medicinal benefits of these compounds may open new pathways for complementary or alternative strategies in the prevention and treatment of ocular diseases.},
}
@article {pmid40941740,
year = {2025},
author = {Fırat, M and Fırat, &#x130;T and Üstündağ, ZF and Öztürk, E and Tuncer, T},
title = {AI-Based Response Classification After Anti-VEGF Loading in Neovascular Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {17},
pages = {},
pmid = {40941740},
issn = {2075-4418},
abstract = {Background/Objectives: Wet age-related macular degeneration (AMD) is a progressive retinal disease characterized by macular neovascularization (MNV). Currently, the standard treatment for wet AMD is intravitreal anti-VEGF administration, which aims to control disease activity by suppressing neovascularization. In clinical practice, the decision to continue or discontinue treatment is largely based on the presence of fluid on optical coherence tomography (OCT) and changes in visual acuity. However, discrepancies between anatomic and functional responses can occur during these assessments. Methods: This article presents an artificial intelligence (AI)-based classification model developed to objectively assess the response to anti-VEGF treatment in patients with AMD at 3 months. This retrospective study included 120 patients (144 eyes) who received intravitreal bevacizumab treatment. After bevacizumab loading treatment, the presence of subretinal/intraretinal fluid (SRF/IRF) on OCT images and changes in visual acuity (logMAR) were evaluated. Patients were divided into three groups: Class 0, active disease (persistent SRF/IRF); Class 1, good response (no SRF/IRF and ≥0.1 logMAR improvement); and Class 2, limited response (no SRF/IRF but with <0.1 logMAR improvement). Pre-treatment and 3-month post-treatment OCT image pairs were used for training and testing the artificial intelligence model. Based on this grouping, classification was performed with a Siamese neural network (ResNet-18-based) model. Results: The model achieved 95.4% accuracy. The macro precision, macro recall, and macro F1 scores for the classes were 0.948, 0.949, and 0.948, respectively. Layer Class Activation Map (LayerCAM) heat maps and Shapley Additive Explanations (SHAP) overlays confirmed that the model focused on pathology-related regions. Conclusions: In conclusion, the model classifies post-loading response by predicting both anatomic disease activity and visual prognosis from OCT images.},
}
@article {pmid40940771,
year = {2025},
author = {Francelin, C and Qi, X and Godoy, J and Bicknell, BT and Prasad, R and Grant, MB and Boulton, ME},
title = {Impact of Donor and Host Age on Systemic Cell Therapy to Treat Age-Related Macular Degeneration.},
journal = {Cells},
volume = {14},
number = {17},
pages = {},
pmid = {40940771},
issn = {2073-4409},
support = {P30 AI027767/AI/NIAID NIH HHS/United States ; R01 EY033620/EY/NEI NIH HHS/United States ; R01 EY012601/EY/NEI NIH HHS/United States ; P30 CA013148/CA/NCI NIH HHS/United States ; R01 EY032753/EY/NEI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01EY036588/EY/NEI NIH HHS/United States ; R01 EY028037/EY/NEI NIH HHS/United States ; R01 EY028858/EY/NEI NIH HHS/United States ; R01EY012601/EY/NEI NIH HHS/United States ; R01 EY025383/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Macular Degeneration/therapy/pathology ; Mice ; *Cell- and Tissue-Based Therapy/methods ; Superoxide Dismutase/metabolism/genetics ; Retinal Pigment Epithelium/pathology/metabolism ; Mice, Inbred C57BL ; *Aging ; Disease Models, Animal ; Age Factors ; Hematopoietic Stem Cells/cytology/metabolism ; Retina/pathology ; },
abstract = {Purpose: We previously reported that the systemic administration of preprogrammed mouse hematopoietic bone marrow-derived progenitor cells (HSPCs) improved visual function and restored a functional retinal pigment epithelial (RPE) layer. Here, we investigated the potential impact of donor vs. host age on systemic cellular therapy in a murine model of retinal degeneration. Methods: HSPCs from young (8 weeks) and old (15 months) mice were programmed ex vivo with a lentiviral vector expressing the RPE65 gene (LV-RPE65) and systemically administering into young or old SOD2 KD mice. Visual loss and pathological changes were evaluated by electroretinogram (ERG), optical coherence tomography (OCT), histology, and immunohistochemistry. Results: Old donor HSPCs administered to old manganese superoxide dismutase (SOD2) knockdown (KD) recipient mice offered the least benefit. This was exemplified by the reduced recruitment and incorporation of LV-RPE65 HSPC into the RPE layer, as well as decreased improvement in visual function, retinal thinning, and limited reduction in oxidative damage and microglial activation. LV-RPE65 HSPC from young mice incorporated into the RPE layer of old SOD2 KD mice, though to a lesser extent than young cells administered to young hosts, offered some level of protection. By contrast, LV-RPE65 HSPCs from old mice, located to the subretinal space of young host mice, reduced visual loss, although some retinal pathology was observed. Conclusions: The administration of LV-RPE65 HSPC from old donors to old SOD2 KD mice offered the least improvement. Translational Relevance: Our findings highlight how both donor and recipient age impact the success of HSPC-based retinal therapy and using cells from aged donors for AMD treatment may have some limitations.},
}
@article {pmid40940727,
year = {2025},
author = {Lalman, C and Yang, Y and Walker, JL},
title = {Artificial Intelligence in Ocular Transcriptomics: Applications of Unsupervised and Supervised Learning.},
journal = {Cells},
volume = {14},
number = {17},
pages = {},
pmid = {40940727},
issn = {2073-4409},
mesh = {Humans ; *Supervised Machine Learning ; *Transcriptome/genetics ; *Gene Expression Profiling/methods ; *Artificial Intelligence ; *Unsupervised Machine Learning ; *Eye/metabolism ; *Eye Diseases/genetics ; Macular Degeneration/genetics ; },
abstract = {Transcriptomic profiling is a powerful tool for dissecting the cellular and molecular complexity of ocular tissues, providing insights into retinal development, corneal disease, macular degeneration, and glaucoma. With the expansion of microarray, bulk RNA sequencing (RNA-seq), and single-cell RNA-seq technologies, artificial intelligence (AI) has emerged as a key strategy for analyzing high-dimensional gene expression data. This review synthesizes AI-enabled transcriptomic studies in ophthalmology from 2019 to 2025, highlighting how supervised and unsupervised machine learning (ML) methods have advanced biomarker discovery, cell type classification, and eye development and ocular disease modeling. Here, we discuss unsupervised techniques, such as principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), uniform manifold approximation and projection (UMAP), and weighted gene co-expression network analysis (WGCNA), now the standard in single-cell workflows. Supervised approaches are also discussed, including the least absolute shrinkage and selection operator (LASSO), support vector machines (SVMs), and random forests (RFs), and their utility in identifying diagnostic and prognostic markers in age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, keratoconus, thyroid eye disease, and posterior capsule opacification (PCO), as well as deep learning frameworks, such as variational autoencoders and neural networks that support multi-omics integration. Despite challenges in interpretability and standardization, explainable AI and multimodal approaches offer promising avenues for advancing precision ophthalmology.},
}
@article {pmid40940720,
year = {2025},
author = {Mohanna, S and Eppenberger, LS and Pfäffli, O and Ferdowsi, S and Simon-Zoula, S and Amstutz, C and Bachmann, LM and Thiel, MA and Schmid, MK},
title = {High-Resolution Adaptive Optics Transscleral Flood Illumination Imaging Allows Phenotyping of Age-Related Macular Degeneration.},
journal = {Cells},
volume = {14},
number = {17},
pages = {},
pmid = {40940720},
issn = {2073-4409},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/pathology ; Tomography, Optical Coherence/methods ; Aged ; Female ; Male ; Phenotype ; Retinal Pigment Epithelium/diagnostic imaging/pathology ; Aged, 80 and over ; Middle Aged ; },
abstract = {Adaptive optics transscleral flood illumination (AO-TFI) enables in vivo imaging of the retinal pigment epithelium (RPE) at near-cellular resolution. In this study, we evaluated its potential as a phenotyping tool in age-related macular degeneration (AMD) by analyzing disease-associated structural patterns and their correlation with optical coherence tomography (OCT) features. We examined AO-TFI images from 120 eyes diagnosed with either early-to-advanced dry AMD (including geographic atrophy, GA) or neovascular AMD (nvAMD). Images were graded by a masked reader, and patterns were matched to corresponding OCT findings. Four consistent morphologic patterns were identified: atrophy, pre-atrophy, soft drusen, and reticular pseudodrusen. Morphometric quantification of hyporeflective regions showed progressive changes in perimeter, diameter, and area from reticular pseudodrusen to soft drusen and pre-atrophy, returning to lower values in atrophy. Distinct nvAMD-specific signatures were not identified. AO-TFI offers a practical, high-resolution complement to OCT, AO-SLO, and AO-OCT for phenotypic characterization of AMD in clinical settings.},
}
@article {pmid40939951,
year = {2025},
author = {Vance, E and von der Emde, L and Mukherjee, S and Hou, J and Domalpally, A and Chew, EY and Chakravarthy, U and Keenan, TDL and , },
title = {Risk Factors for 15-Letter Visual Acuity Loss from Geographic Atrophy Progression over 1 Year in the Age-Related Eye Disease Study 2.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
pmid = {40939951},
issn = {2468-6530},
support = {Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; ZIA EY000485/ImNIH/Intramural NIH HHS/United States ; },
abstract = {PURPOSE: A change of ≥15 letters in best-corrected visual acuity (BCVA) is typically defined as clinically significant by regulatory agencies, but risk factors for rapid 15-letter loss in geographic atrophy (GA) are poorly understood. The purpose was to identify independent risk factors for 15-letter loss within 1 year in eyes with GA.<br><br>DESIGN: Post hoc analysis of the Age-Related Eye Disease Study 2.<br><br>PARTICIPANTS: Nine hundred sixty-one eyes (743 participants).<br><br>METHODS: Annual fundus photographs were graded for GA presence/morphology. Best-corrected visual acuity was measured using the ETDRS chart. Multivariable analyses comprised logistic regression for 15-letter loss within 1 year, based on (1) baseline variables (demographic, BCVA, and GA morphology variables, defined at first time point with GA), (2) genetic variables (CFH Y402H and ARMS2), and (3) GA enlargement rate (from first time point with GA).<br><br>MAIN OUTCOME MEASURES: Fifteen-letter loss in BCVA within 1 year.<br><br>RESULTS: During 1-year follow-up, BCVA declined by &#x2265;15 letters in 53 eyes (5.5%). In a model with baseline variables, the risk factors were as follows: age (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 1.04-1.14; P = 0.0005), closer GA proximity to fovea (aOR, 0.90 per 0.1 mm increase; 95% CI, 0.84-0.97; P = 0.005), current smoking (aOR, 3.85; 95% CI, 1.49-9.97; P = 0.005), and BCVA <20/40 (aOR, 2.09; 95% CI, 1.17-3.74; P = 0.013). In a model with baseline variables and genotype, CFH was a risk factor (aOR, 4.63; 95% CI, 1.27-16.9; P = 0.020; 2 vs. 0 risk alleles), whereas ARMS2 was not. In a model with baseline variables and GA enlargement rate, faster enlargement was a risk factor (aOR, 1.12 per 0.1 mm/year increase; 95% CI, 1.07-1.18; P < 0.0001).<br><br>CONCLUSIONS: We identified multiple independent risk factors for rapid, clinically significant BCVA loss in GA. We also developed clinically relevant models for different scenarios. These can guide the design and interpretation of interventional trials aimed at decreasing vision loss in GA and provide prognostic information in clinical practice. The risk factors for BCVA loss and faster GA enlargement overlap only partially, so that trial inclusion criteria, power calculations, and covariate adjustment should differ according to the choice of a functional versus structural measure as the primary end point.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40938387,
year = {2025},
author = {Jauch, AS and Saßmannshausen, M and Chang, P and von der Emde, L and Pfau, M and Holz, FG and Ach, T},
title = {[Progression assessment for geographic atrophy].},
journal = {Die Ophthalmologie},
volume = {122},
number = {10},
pages = {773-781},
pmid = {40938387},
issn = {2731-7218},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; Disease Progression ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Artificial Intelligence ; },
abstract = {In addition to the development of macular neovascularization (MNV), geographic atrophy (GA) is one of the late stages of age-related macular degeneration (AMD) and can lead to irreversible severe visual impairment. Standardized and precise quantification of GA areas, based primarily on fundus autofluorescence and optical coherence tomography (OCT) imaging, is important for progression monitoring. Various factors such as foveal involvement, lesion location, focality of GA and perilesional autofluorescence patterns play an important role in the assessment of GA progression. Automated analytical techniques based on artificial intelligence (AI) are emerging in the detection, assessment, quantification and prediction of disease progression. As there is currently no causal therapy for GA, measuring progression in GA is becoming increasingly more important in order to monitor current treatment options with complement inhibitors and to test in studies novel therapeutic approaches to slow down the course of the disease. A progression analysis based on structural and functional degeneration parameters could optimize the counselling of patients, treatment decisions and patient monitoring in the future.},
}
@article {pmid40934544,
year = {2025},
author = {Yabaş, A and Karabaş, VL and Furat, S and Tokuç, E&#xd6; and Öztürk, A and Altuntaş, C and Özsoy, &#xd6;D and Duruksu, G and Yazır, Y},
title = {Investigation of the effects of resveratrol, lutein, and crocetin on ARPE-19 cells induced with oxidative damage by H2O2.},
journal = {Tissue &amp; cell},
volume = {98},
number = {},
pages = {103133},
doi = {10.1016/j.tice.2025.103133},
pmid = {40934544},
issn = {1532-3072},
abstract = {OBJECTIVE: This study aimed to evaluate and compare the antioxidant effects, influence on autophagy and mitophagy, and impact on cell viability of resveratrol, lutein, and crocetin in hydrogen peroxide (H2O2)-induced oxidative damage in ARPE-19 cells as an in vitro model of age-related macular degeneration (AMD).<br><br>METHODS: Oxidative damage was induced in ARPE-19 cells by exposure to 800&#x202f;&#x3bc;M H&#x2082;O&#x2082; for 1&#x202f;h. Cell viability was assessed using the WST-1 assay. Subsequently, ARPE-19 cells were treated with lutein (5 and 10&#x202f;&#x3bc;M), crocetin (10 and 20&#x202f;&#x3bc;M), or resveratrol (100&#x202f;&#x3bc;M), and the levels of oxidative damage biomarkers including malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) were quantified via spectrophotometry. The autophagy- and mitophagy-related markers, LC3B, PINK1, and PARKIN, were visualized using confocal microscopy, and LC3B and PARKIN were further evaluated by western blotting (WB).<br><br>RESULTS: Cell viability results were 100&#x202f;% in the control group, decreased to 73.5&#x202f;% and 69.1&#x202f;% with 10 and 20&#x202f;&#x3bc;M crocetin, 62.7&#x202f;% and 59.3&#x202f;% with 5 and 10&#x202f;&#x3bc;M lutein, and 52.7&#x202f;% with 100&#x202f;&#x3bc;M resveratrol, respectively, while H&#x2082;O&#x2082; exposure reduced viability to 0.04&#x202f;%. Exposure to H&#x2082;O&#x2082; (800&#x202f;&#xb5;M, 1&#x202f;h) induced significant oxidative damage in ARPE-19 cells, as indicated by a reduction in GSH levels (p&#x202f;<&#x202f;0.01) and an increase in MDA (p&#x202f;<&#x202f;0.001) and NO (p&#x202f;<&#x202f;0.001) compared to the control group, along with a notable decrease in WST-1 viability. Among the interventions, 10&#x202f;&#xb5;M crocetin significantly decreased MDA (p&#x202f;=&#x202f;0.019) and NO (p&#x202f;=&#x202f;0.05) levels compared to those in the damage group, although the 20&#x202f;&#xb5;M concentration also reduced these markers without achieving statistical significance. 5&#x202f;&#xb5;M Lutein significantly reduced NO levels compared to the damage group, whereas reductions in MDA at concentrations of 5-10&#x202f;&#xb5;M were not statistically significant. GSH levels exhibited a numerical, albeit non-significant, increase with 10&#x202f;&#xb5;M lutein (p&#x202f;=&#x202f;0.09), and showed modest, non-significant increases with crocetin and resveratrol. The highest LC3B expression was observed in the 5&#x202f;&#x3bc;M lutein group compared to control and other treatment groups, while PARKIN expression was significantly elevated in the 10&#x202f;&#x3bc;M lutein, 20&#x202f;&#x3bc;M crocetin, and 100&#x202f;&#x3bc;M resveratrol groups, with 20&#x202f;&#x3bc;M crocetin and resveratrol levels also exceeding lutein 5&#x202f;&#x3bc;M.<br><br>CONCLUSIONS: 10&#x202f;&#x3bc;M Crocetin demonstrated the strongest antioxidant protection, while 5&#x202f;&#x3bc;M lutein primarily improved cell survival, likely through autophagy activation and 100&#x202f;&#x3bc;M resveratrol also activated both autophagy and mitophagy. These results highlighted the complementary concentration-dependent mechanisms of natural antioxidants in protecting RPE cells from oxidative stress related to AMD.},
}
@article {pmid40933661,
year = {2025},
author = {Cheung, CMG and Jackson, TL and Wykoff, CC and Khanani, AM and Leitch, IM and Baldwin, ME and Slakter, J},
title = {Sozinibercept (Anti-VEGF-C/-D) Combined with Ranibizumab for Polypoidal Choroidal Vasculopathy: Phase IIb Predefined Subgroup Analysis.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100759},
pmid = {40933661},
issn = {2666-9145},
abstract = {PURPOSE: The aim of this study was to assess the efficacy of sozinibercept, a novel "trap" inhibitor of VEGF-C and VEGF-D, when combined with ranibizumab for the treatment of polypoidal choroidal vasculopathy (PCV).<br><br>DESIGN: Prespecified subgroup analysis of a randomized, double-masked, sham-controlled phase IIb trial.<br><br>PARTICIPANTS: Adults with treatment-na&#xef;ve neovascular age-related macular degeneration.<br><br>METHODS: Participants were randomized 1:1:1 to receive a total of 6 intravitreal injections of ranibizumab 0.5 mg given 4-weekly, in combination with either 0.5 mg sozinibercept, 2 mg sozinibercept, or sham injection (control). Active PCV was determined at baseline by masked readers at an independent imaging center based on multimodal imaging, including OCT (notched, sharply peaked, or multilobular pigment epithelial detachments with or without a ring of hyperreflectivity along the inner border), fundus photography (subretinal orange nodules), and fluorescein angiography (typical primarily occult multifocal lesions).<br><br>MAIN OUTCOME MEASURES: The primary end point was mean change from baseline in best-corrected visual acuity (BCVA) through week 24. Secondary end points included categorical changes in BCVA from baseline, anatomical changes in lesion morphology, and safety.<br><br>RESULTS: Of 366 participants, PCV was identified in 66 (18%) using predefined criteria. Sozinibercept combination therapy produced a dose response, with a mean BCVA change from baseline to week 24 of +13.54 (2 mg, n = 22) and +10.87 (0.5 mg, n = 24) letters compared with +6.9 letters for ranibizumab (n = 20), respectively. The 2 mg sozinibercept combination group had a superior BCVA gain versus ranibizumab (+6.7 letter difference in least squares mean; P = 0.0253) with more participants gaining &#x2265;10 letters (77.3 vs. 47.4%) and &#x2265;15 letters (40.9 vs. 31.6%) and fewer losing &#x2265;5 letters (4.5 vs. 15.8%). Anatomic responses were consistent with functional outcomes and at week 24, fewer participants in the 2 mg sozinibercept combination group had subretinal fluid (19%) or intraretinal cysts (9.1%) than with ranibizumab monotherapy (42.1% and 25%, respectively). The safety profile of sozinibercept combination therapy was similar to ranibizumab.<br><br>CONCLUSIONS: In this predefined phase IIb subgroup of patients with PCV, sozinibercept combination therapy through inhibition of VEGF-C/-D achieved improved visual and anatomic outcomes compared with ranibizumab monotherapy consistent with the overall population.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40932714,
year = {2025},
author = {Kim, MS and Nam, S and Lee, J and Woo, SJ},
title = {Antithrombotic Medications and Intraocular Hemorrhage Risk in Exudative Age-Related Macular Degeneration.},
journal = {JAMA network open},
volume = {8},
number = {9},
pages = {e2531366},
pmid = {40932714},
issn = {2574-3805},
mesh = {Humans ; Male ; Female ; Aged ; Retrospective Studies ; *Anticoagulants/adverse effects/therapeutic use ; *Macular Degeneration/complications/drug therapy ; *Platelet Aggregation Inhibitors/adverse effects/therapeutic use ; *Eye Hemorrhage/epidemiology/chemically induced ; Aged, 80 and over ; Middle Aged ; Risk Factors ; *Fibrinolytic Agents/adverse effects/therapeutic use ; Incidence ; Republic of Korea/epidemiology ; Vitrectomy/statistics &amp; numerical data ; Cross-Sectional Studies ; Case-Control Studies ; Longitudinal Studies ; Proportional Hazards Models ; },
abstract = {IMPORTANCE: Although the use of anticoagulants or antiplatelets is known to increase bleeding risk, there is limited evidence on whether they contribute to a higher incidence of intraocular hemorrhage in patients with age-related macular degeneration (AMD).<br><br>OBJECTIVE: To examine the association between anticoagulant or antiplatelet use and clinically important intraocular hemorrhage requiring vitrectomy in patients with exudative AMD.<br><br>In this nationwide, population-based, retrospective cohort study using the Korean Health Insurance Review and Assessment Service database, 149&#x202f;620 patients with exudative AMD older than 40 years were identified from May 1, 2014, to April 30, 2023.<br><br>EXPOSURES: Use of anticoagulants or antiplatelets.<br><br>MAIN OUTCOMES AND MEASURES: The main study outcome was clinically important intraocular hemorrhage requiring vitrectomy. The analysis used a retrospective, longitudinal cohort study design using Cox proportional hazards regression analysis and Kaplan-Meier survival analyses (exposure vs nonexposure group) and a cross-sectional case-control study design using logistic regression analysis (hemorrhage vs no hemorrhage group). All analyses were adjusted for demographics and comorbidities.<br><br>RESULTS: A total of 94&#x202f;449 patients (mean [SD] age, 71.8 [9.8] years; 55&#x202f;677 [59.0%] male) were included in the cohort study, and 8110 patients (mean [SD] age, 70.2 [9.6] years; 5090 [62.8%] male) were included in the case-control study. In the Cox proportional hazards regression analysis, anticoagulant or antiplatelet exposure was associated with a higher risk of intraocular hemorrhage requiring vitrectomy (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29). The incidence probability of intraocular hemorrhage requiring vitrectomy was higher in the exposure group than the nonexposure group. In the logistic analysis, the use of anticoagulants (adjusted odds ratio [aOR], 1.88; 95% CI, 1.45-2.44) or antiplatelets (aOR, 1.37; 95% CI, 1.19-1.57) was associated with intraocular hemorrhage requiring vitrectomy. The combined use of anticoagulants and antiplatelets showed the highest aOR (aOR, 2.28; 95% CI, 1.65-3.15). Higher medication adherence was also associated with a higher aOR of intraocular hemorrhage (aOR, 1.69; 95% CI, 1.45-1.97).<br><br>CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of patients with exudative AMD, antithrombotic medications were associated with a higher risk of intraocular hemorrhage requiring vitrectomy. These results suggest the need for proactive communication and tailored monitoring strategies to help minimize such sight-threatening complications.},
}
@article {pmid40932447,
year = {2025},
author = {Lin, T and Leng, T},
title = {Code-Free Machine Learning for the Detection of Common Ophthalmic Diseases.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {9},
pages = {16},
pmid = {40932447},
issn = {2164-2591},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Machine Learning ; *Diabetic Retinopathy/diagnosis ; *Glaucoma/diagnosis ; *Macular Degeneration/diagnosis ; *Eye Diseases/diagnosis ; Photography ; Fundus Oculi ; },
abstract = {PURPOSE: We explore a code-free method enabling physicians without programming experience to develop machine learning (ML) models for detecting diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma from fundus photographs.<br><br>METHODS: Two classification models were developed using Google Vertex AI's no-code AutoML Vision platform: a binary model detecting any pathology and a multi-class model classifying specific diseases. The development dataset consisted of 800 fundus photography images (200 each of DR, AMD, glaucoma, and normal) from the publicly available Fundus Image dataset for Vessel Segmentation. Ten percent of the dataset was saved for testing and 10% for internal validation. External validation was performed using the Eye Disease Diagnosis and Fundus Synthesis dataset, from which 100 single-diagnosis images per class were randomly selected (total N = 400). Model performances were evaluated using area under the precision-recall curve (AUPRC), precision, recall, accuracy, F1 score, and confidence score analysis.<br><br>RESULTS: Internally, the binary model yielded an AUPRC of 0.967, with 95.0% precision and recall. The multi-class model had an AUPRC of 0.906, with 91.0% precision and 90.0% recall. On external validation, the binary model reached 92.3% accuracy, whereas the multi-class model achieved 90% overall accuracy.<br><br>CONCLUSIONS: Code-free ML approaches can enable physicians to create ML models for retinal disease detection without requiring programming expertise, supporting early detection of eye diseases.<br><br>TRANSLATIONAL RELEVANCE: This work bridges the gap between AI research and clinical deployment by demonstrating that physicians can independently build ML models using accessible, no-code tools.},
}
@article {pmid40931816,
year = {2025},
author = {Lee, YT and Wu, JY and Chang, TW and Hung, CH},
title = {Impact of SGLT2 inhibitors on the risk of age-related ocular diseases in patients with type 2 diabetes mellitus: A target trial emulation study.},
journal = {Diabetes, obesity &amp; metabolism},
volume = {27},
number = {12},
pages = {7299-7308},
doi = {10.1111/dom.70131},
pmid = {40931816},
issn = {1463-1326},
mesh = {Humans ; *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Female ; Male ; Aged ; Retrospective Studies ; Middle Aged ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; *Macular Degeneration/epidemiology/prevention &amp; control ; Risk Factors ; Aged, 80 and over ; *Eye Diseases/epidemiology/prevention &amp; control ; },
abstract = {AIMS: Chronic ocular diseases such as age-related macular degeneration (AMD) are leading causes of vision loss in older adults. While sodium-glucose co-transporter 2 inhibitors (SGLT2i) are widely prescribed in the management of type 2 diabetes mellitus (T2DM), their effects on ocular disease risk remain largely unknown.<br><br>MATERIALS AND METHODS: This retrospective cohort study evaluated the association between SGLT2i use and the risk of AMD and other age-related ocular conditions in adults aged &#x2265;60 with T2DM, using a target trial emulation framework based on the TriNetX global health research network (2013-2025). Patients initiating SGLT2i or dipeptidyl peptidase-4 inhibitors (DPP4i) were propensity-matched 1:1. Primary outcomes were incident non-exudative, exudative, and atrophic AMD, and secondary outcomes included cataract, ocular hypertension, and primary open-angle glaucoma.<br><br>RESULTS: In 12&#x2009;156 matched patients, SGLT2i use was associated with significantly lower risks of non-exudative AMD (HR 0.64; 95% CI 0.49-0.84) and exudative AMD (HR 0.56; 95% CI 0.33-0.96) compared with DPP4i use. A slight increase in the risk of cataract was observed (HR 1.08; 95% CI 1.02-1.15), while no significant differences were found for atrophic AMD, ocular hypertension, or glaucoma.<br><br>CONCLUSIONS: These findings suggest that SGLT2i may offer retinal protective effects in older adults with T2DM, supporting further mechanistic and prospective clinical studies.},
}
@article {pmid40930272,
year = {2025},
author = {Sun, H and Li, B and Gu, Y and Li, F and Di, G and Chen, P},
title = {Imbalanced mitochondrial homeostasis in ocular diseases: unique pathogenesis and targeted therapy.},
journal = {Experimental eye research},
volume = {260},
number = {},
pages = {110632},
doi = {10.1016/j.exer.2025.110632},
pmid = {40930272},
issn = {1096-0007},
mesh = {Humans ; *Homeostasis/physiology ; *Mitochondria/metabolism ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism ; *Eye Diseases/metabolism ; Animals ; *Mitochondrial Diseases/metabolism ; },
abstract = {Mitochondria play a crucial role in energy production and are intimately associated with ocular function. Mitochondrial dysfunction can trigger oxidative stress and inflammation, adversely affecting key ocular structures such as the lacrimal gland, lens, retina, and trabecular meshwork. This dysfunction may compromise the barrier properties of the trabecular meshwork, impeding aqueous humour outflow, elevating intraocular pressure, and resulting in optic nerve damage and primary open-angle glaucoma. Additionally, impaired mitochondrial homeostasis can contribute to dry eye, cataracts, and age-related macular degeneration (AMD) by disrupting the function of the lacrimal gland, lens, and macula. Imbalanced mitochondrial homeostasis primarily involves four pathological features: disruption of mitochondrial quality control, mitochondrial damage (inducing inflammation), excessive production of mitochondrial reactive oxygen species (ROS) (initiating oxidative stress), and disturbances in mitochondrial calcium (Ca[2+]) homeostasis. Oxidative stress and inflammation are central mechanisms of cellular injury. Pharmacological strategies aimed at reducing excessive ROS, restoring redox balance, and mitigating oxidative and inflammatory damage show therapeutic promise. Moreover, enhancing mitochondrial function through pharmacological agents, replacing damaged mitochondria, and promoting mitochondrial rejuvenation represent emerging treatment avenues. This review explores the relationship between mitochondrial dysfunction and ocular diseases such as dry eye, glaucoma, cataracts, and AMD, with a focus on associated mechanisms and potential therapeutic interventions.},
}
@article {pmid40928311,
year = {2025},
author = {Chen, C and Xie, T and Zhang, H and Chang, L and Lan, Y and Fan, C and Wei, D and Wang, X and Liu, S and Chen, Y and Chen, Y and Wang, X and Yan, X and Shang, L and Tao, L and Han, J},
title = {Na-Cl Cotransporter (SLC12A3) Inhibition Exacerbates Age-Related Macular Degeneration Via the Nrf2/HO-1 Ferroptosis Pathway.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {12},
pages = {24},
pmid = {40928311},
issn = {1552-5783},
mesh = {*Macular Degeneration/metabolism/genetics/chemically induced ; *NF-E2-Related Factor 2/metabolism/genetics ; Humans ; Animals ; Mice ; *Ferroptosis/drug effects/physiology ; Oxidative Stress/drug effects ; *Heme Oxygenase-1/metabolism/genetics ; Cross-Sectional Studies ; *Sodium Chloride Symporter Inhibitors/pharmacology/adverse effects ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Male ; Mice, Inbred C57BL ; Antihypertensive Agents/adverse effects/pharmacology ; Female ; Signal Transduction ; Aged ; Disease Models, Animal ; },
abstract = {PURPOSE: To explore the causal links between antihypertension drugs usage and age-related macular degeneration (AMD).<br><br>METHODS: Multiple genetic analyses, including summary data-based Mendelian randomization (SMR), traditional MR, and colocalization analysis, were used to explore the causal associations between antihypertension drugs and AMD. Clinical data from the UK Biobank and the National Health and Nutrition Examination Survey (NHANES) was applied to refined risk assessment of specific antihypertensive medications in the context of AMD development. In vitro and in vivo oxidative stress models, mediated by NaIO3, were utilized to study the impact of specific antihypertensive drugs and target genes on AMD pathogenesis.<br><br>RESULTS: Genetic analyses substantiated the causal relationship between increased SLC12A3 expression and a lowered AMD risk. Colocalization analysis supported the shared causal attributes between SLC12A3 expression and AMD. Cross-sectional analysis results based on UK Biobank indicated that AMD risk was significantly lower in participants taking thiazide diuretics with other antihypertensives or not on antihypertensives compared to those on thiazides alone. The results based on NHANES support the above results. In vivo and in vitro experiments showed that thiazide diuretics worsened retinal damage in AMD mouse models, and SLC12A3 knockdown disrupted the balance of oxidative stress in retinal pigment epithelium (RPE) cells. Further molecular mechanism experiments showed that SLC12A3 knockdown promoted retinal degeneration by regulating RPE ferroptosis through activation of the Nrf2/HO-1 pathway.<br><br>CONCLUSIONS: Our study underscores a notable causal association between thiazide diuretic use and AMD risk and reveals a potential mechanism by which inhibition or downregulation of SLC12A3 (sodium-chloride cotransporter [NCC]) contributes to AMD progression. However, deeper exploration is needed to enhance the accuracy and validity of our findings.},
}
@article {pmid40927851,
year = {2024},
author = {Lippera, M and Feo, A and Del Turco, C and Santoru, F and Fossati, G and Zollet, P and Panico, E and Romano, MR and Querques, G and Panico, C and La Spina, C},
title = {Modified pro re nata regimen of brolucizumab in treatment-naive neovascular age-related macular degeneration.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001692},
pmid = {40927851},
issn = {1937-1578},
abstract = {PURPOSE: To study the efficacy and safety of pro re nata regimen of brolucizumab, without loading dose, in treatment-naive patients with neovascular age-related macular degeneration (nAMD).<br><br>CASE SERIES: Retrospective, observational study. We included all consecutive patients diagnosed with treatment- na&#xef;ve nAMD undergoing Brolucizumab in Humanitas eye clinic, Turin, Italy between April 2022 and May 2023. Treatment was performed following pro re nata regimen without loading phase. Injection intervals (time between two injections), adverse events, changes in best corrected visual acuity (BCVA), central macular thickness (CMT), maximal retinal thickness (MRT), intraretinal and subretinal fluid (IRF, SRF) were evaluated descriptively up to one year after the first injection. Twenty-one eyes of 21 patients were included in the study. The mean number of injections was 2.4&#xb1;0.7 at 3 month, 3.0&#xb1;2.0 at 6 month, 3.1&#xb1;2.4 at 9 month and 3.8&#xb1;2.8 at 12 month, respectively. BCVA significantly improved from 20/80 Snellen (0.6&#xb1;0.3 LogMar) to 20/50 Snellen (0.4&#xb1;0.3 LogMar) at month 12 (p = 0.044). CMT and MRT significantly reduced from 426 &#x3bc;m and 606 &#x3bc;m at baseline, to 248 &#x3bc;m and 356 &#x3bc;m at one-year follow-up (p=0.00067 and p=0.02, respectively). SRF and IRF also progressively resolved. On the other hand, intraocular inflammation (IOI) events occurred in 9.5% of cases during follow-up. IOI resolved in all cases with prompt treatment without visual sequelae.<br><br>CONCLUSIONS: In our study, pro re nata regimen of brolucizumab without loading phase appears to be an effective treatment option in treatment-naive nAMD patients, with IOI rate similar to the one reported in trials and lower number of injections.},
}
@article {pmid40925810,
year = {2025},
author = {Zhang, KR and Nair, RM and Chen, Y and Jin, F and Dunaief, JL and VanderBeek, BL},
title = {Oral Ursodeoxycholic Acid Is Associated With Decreased Rate of AMD.},
journal = {Clinical therapeutics},
volume = {47},
number = {11},
pages = {1024-1027},
doi = {10.1016/j.clinthera.2025.08.010},
pmid = {40925810},
issn = {1879-114X},
mesh = {Humans ; *Ursodeoxycholic Acid/administration &amp; dosage/therapeutic use ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; *Macular Degeneration/prevention &amp; control/epidemiology ; *Cholelithiasis/drug therapy/complications ; Administration, Oral ; *Cholagogues and Choleretics/administration &amp; dosage/therapeutic use ; Proportional Hazards Models ; Cholecystectomy ; Disease Progression ; },
abstract = {PURPOSE: Cholelithiasis is associated with decreased risk of age-related macular degeneration (AMD). Ursodeoxycholic acid (UDCA), a bile acid used to dissolve cholesterol gallstones, has been shown to be retina-protective in several mouse models. This study sought to determine if UDCA may protect against AMD.<br><br>METHODS: A retrospective cohort study was conducted using data between January 1, 2000 to June 30, 2022 in Optum's de-identified Clinformatics Data Mart database. All patients had a history of cholelithiasis, cholecystitis, or cholecystectomy. The exposed cohort included patients taking UDCA. Controls did not take UDCA and were matched 1:3 for age (&#xb1;3 years), sex, race, type of gallbladder disease, and insurance coverage start and end date (&#xb1;4 months). All included patients were 55 years old or older, had at least two years of data in the dataset, and no prior history of AMD. Inverse probability of treatment weighting (IPTW) was used to balance covariates at baseline. Cox proportional hazard regression modeling with IPTW was used to compare progression to AMD between the cohorts.<br><br>FINDINGS: A total of 5,863 patients taking UDCA and 17,164 matched controls were analyzed. In both cohorts after IPTW, roughly 56% of patients had cholelithiasis, 16% had cholecystitis, and 28% had cholecystectomy. Age and sex were balanced at baseline between cohorts (UDCA: 70.5 &#xb1; 9.54 years old and 58.6% female; controls: 70.3 &#xb1; 9.59 years old and 57.4% female). In the UDCA cohort, 384/5,705 (6.74%) were diagnosed with AMD. In the control cohort, 1,559/17,322 (9.00%) were diagnosed with AMD. This corresponded to a significantly decreased hazard of AMD (adjusted hazard ratio = 0.65, 95% CI: 0.58-0.74, P < 0.0001).<br><br>IMPLICATIONS: UDCA was associated with a 35% reduction in the hazard of AMD in patients with underlying gallbladder disease. Determining the mechanism for this protective effect could improve understanding of AMD pathogenesis. These results also suggest that clinical trials evaluating the use of UDCA for AMD could be valuable.},
}
@article {pmid40924919,
year = {2025},
author = {Chan, HH and Feo, A and Cabral, D and Bousquet, E and Popovic, MM and Marin, AI and Quarta, A and El-Haig, WM and Chong Teo, KY and Tan, ACS and Gemmy Cheung, CM and Querques, G and Govetto, A and Romano, MR and Mastropasqua, R and Sadda, SR and Sarraf, D},
title = {Type 4 Macular Neovascularization (NV): A New Member of the Optical Coherence Tomography (OCT) Classification of NV Age-Related Macular Degeneration (AMD).},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004664},
pmid = {40924919},
issn = {1539-2864},
abstract = {PURPOSE: To describe the clinical and multimodal imaging features of a novel form of macular neovascularization (MNV), designated Type 4 MNV, defined by mixed Type 1 and Type 2 neovascularization (NV), extensive intraretinal anastomotic NV, and central posterior hyaloid fibrosis (CPHF).<br><br>METHODS: This multicenter retrospective observational case series included patients with neovascular age-related macular degeneration (AMD) exhibiting both Type 1 and 2 MNV and an overlying anastomotic intraretinal NV network. This was confirmed with OCT and OCT angiography (OCTA). Demographics, baseline visual acuity (VA), and OCT imaging biomarkers including the hyperreflective oblique band (HOB) sign, CPHF, epiretinal membrane (ERM), and OCTA NV subtype were assessed.<br><br>RESULTS: Eleven eyes from eleven patients (mean age: 76.9 years; 36.4% female) met inclusion criteria. Baseline VA was logMAR 1.56 &#xb1; 0.45 (&#x2248;20/630) and 90.9% of subjects presented with severe visual loss. All eyes showed the HOB sign. CPHF was observed in 81.8% (9/11 subjects). ERM with radial traction was present in 81.8%. OCTA illustrated mixed Type 1 and 2 MNV with a prominent overlying intraretinal anastomotic network extending into the preretinal space.<br><br>CONCLUSION: Type 4 MNV represents a distinct AMD phenotype with aggressive anatomical features including mixed Type 1 and 2 MNV, inner retinal and preretinal proliferation and anastomosis and retinal disorganization. The visual prognosis is invariably poor with recalcitrance to anti-VEGF therapy. The recognition of this signature NV lesion subtype further refines the MNV classification system and can impact therapeutic strategies for neovascular AMD.},
}
@article {pmid40923045,
year = {2025},
author = {Rothbächer, J and Khalil, H and Eidherr, M and Bolz, M},
title = {Additional Effects of Faricimab in Aflibercept Low-Responders: Retinal Morphology and Function in Eyes with Neovascular Age Related Macular Degeneration Following a Switch Between Two Anti-VEGF Agents.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3145-3152},
pmid = {40923045},
issn = {1177-5467},
abstract = {PURPOSE: To assess how transitioning from an Aflibercept to a Faricimab intravitreal treatment impacts retinal structures and functional aspects in patients with neovascular age related macular degeneration (nAMD) in a real-life setting.<br><br>PATIENTS AND METHODS: A retrospective clinical study including 49 patients (57 eyes) with nAMD at the Department of Ophthalmology and Optometry, Kepler University Hospital, Linz, Austria was performed. The patients, who had previously been receiving monthly Aflibercept injections with an unsatisfactory treatment response, were switched to intravitreal Faricimab and followed-up between 12/2022 and 12/2023.<br><br>RESULTS: The mean treatment-interval before the fifth injection with Faricimab was 5.35 &#xb1; 1.49&#xa0;weeks and was therefore significantly longer compared to the monthly interval with Aflibercept (p < 0.001). Mean baseline central retinal thickness (CRT) was 267.82 &#xb1; 76.00&#xa0;&#xb5;m and decreased significantly already at month 1 to 249.61 &#xb1; 65.35&#xa0;&#xb5;m (p < 0.001). After the fourth intravitreal injection, there was no significant change with a CRT of 252.95 &#xb1; 56.96&#xa0;&#xb5;m (p = 0.134). There was a significant reduction in the number of patients showing subretinal fluid (SRF) and intraretinal fluid (IRF). In eyes with fibrovascular pigment epithelium detachment (PED), an interval extension was not possible in more than half of the cases. Eyes with serous and drusenoid PED and a rather high amount of hyper-reflective foci (HRF), the majority showed a significant response after the switch.<br><br>CONCLUSION: An initial loading dose could be beneficial to elongate Faricimab's additional effect of reducing retinal swelling in eyes with nAMD and previous low-response to Aflibercept. Serous and drusenoid PEDs seem to benefit more than fibrovascular PEDs. A high amount of intraretinal HRF in patients with PED was a sign for good respondence to Faricimab.},
}
@article {pmid40922557,
year = {2025},
author = {Kumar, H and Bagdasarova, Y and Song, S and Hickey, DG and Cohn, AC and Okada, M and Finger, RP and Terheyden, JH and Hogg, RE and Gabrielle, PH and Arnould, L and Jannaud, M and Hadoux, X and van Wijngaarden, P and Abbott, CJ and Hodgson, LAB and Schwartz, R and Tufail, A and Chew, EY and Lee, CS and Fletcher, EL and Bahlo, M and Ansell, BRE and Pébay, A and Guymer, RH and Lee, AY and Wu, Z},
title = {Deep Learning-Based Detection of Reticular Pseudodrusen in Age-Related Macular Degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.14607},
pmid = {40922557},
issn = {1442-9071},
support = {//Research to Prevent Blindness/ ; OT2OD32644/NH/NIH HHS/United States ; R01AG060942/NH/NIH HHS/United States ; //Macular Disease Foundation Australia/ ; APP1027624//National Health and Medical Research Council/ ; GNT1181010//National Health and Medical Research Council/ ; GNT1194667//National Health and Medical Research Council/ ; GNT2008382//National Health and Medical Research Council/ ; },
abstract = {BACKGROUND: Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). This study sought to develop and externally test a deep learning (DL) model to detect RPD on optical coherence tomography (OCT) scans with expert-level performance.<br><br>METHODS: RPD were manually segmented in 9800 OCT B-scans from individuals enrolled in a multicentre randomised trial. A DL model for instance segmentation of RPD was developed and evaluated against four retinal specialists in an internal test dataset. The primary outcome was the performance of the DL model for detecting RPD in OCT volumes in five external test datasets compared to two retinal specialists.<br><br>RESULTS: In an internal test dataset consisting of 250 OCT B-scans, the DL model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC]&#x2009;=&#x2009;0.76) than the agreement amongst the specialists (DSC&#x2009;=&#x2009;0.68; p&#x2009;<&#x2009;0.001). In the five external test datasets consisting of 1017 eyes from 812 individuals, the DL model detected RPD in OCT volumes with a similar level of performance as two retinal specialists (area under the receiver operator characteristic curve [AUC]&#x2009;=&#x2009;0.94, 0.95 and 0.96 respectively; p&#x2009;&#x2265;&#x2009;0.32).<br><br>CONCLUSIONS: We present a DL model for automatic detection of RPD with expert-level performance, which could be used to support the clinical management of AMD. This model has been made publicly available to facilitate future research to understand this critical, yet enigmatic, AMD phenotype.},
}
@article {pmid40922455,
year = {2025},
author = {Abu Ishkheidem, I and Inci, E and Breimer, M and Silfverswärd, ST and Zetterberg, M and Grönlund, MA},
title = {Real-world outcomes of aflibercept 8 mg in patients previously treated for neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.17590},
pmid = {40922455},
issn = {1755-3768},
abstract = {PURPOSE: To evaluate visual, anatomical and safety outcomes of aflibercept 8 mg in previously treated patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective study included nAMD patients switched to aflibercept 8&#x2009;mg from prior anti-VEGF therapies at Sahlgrenska University Hospital between February 2024 and February 2025. Data on best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) height, fluid status, treatment intervals, time to fluid recurrence and adverse events were collected.<br><br>RESULTS: 181 eyes (167 patients; mean age 80.4&#x2009;&#xb1;&#x2009;8.5&#x2009;years; 67.7% female) were included, with a median follow-up of 12.9&#x2009;weeks (range 4.1-48.1). A total of 415 injections were administered (mean 2.1&#x2009;&#xb1;&#x2009;1.5 per eye). BCVA remained stable (baseline 0.46&#x2009;&#xb1;&#x2009;0.31 logMAR; post-treatment 0.47&#x2009;&#xb1;&#x2009;0.37 logMAR; p&#x2009;=&#x2009;0.18). CRT decreased significantly (-19.5&#x2009;&#xb1;&#x2009;47.2&#x2009;&#x3bc;m; p&#x2009;<&#x2009;0.001), as did PED height (-37.4&#x2009;&#xb1;&#x2009;68.4&#x2009;&#x3bc;m; p&#x2009;<&#x2009;0.001). Intraretinal fluid prevalence decreased from 34.3% to 19.3% (p&#x2009;<&#x2009;0.001) and subretinal fluid from 53.0% to 33.7% (p&#x2009;<&#x2009;0.001). The median maximal dry interval achieved was nine weeks, and analysis of interval extension showed a statistically significant mean increase of 1.27&#x2009;&#xb1;&#x2009;4.24&#x2009;weeks overall (p&#x2009;=&#x2009;0.0009), particularly in eyes dry at baseline. The median time to fluid recurrence among those with reactivation was ten weeks. Higher baseline CRT predicted greater CRT reduction (-44.1&#x2009;&#x3bc;m per 100&#x2009;&#x3bc;m increase; p&#x2009;<&#x2009;0.001) but shorter dry intervals. Safety was favourable, with one case (0.6% per eye; 0.2% per injection) of mild anterior uveitis and no cases of intraocular pressure elevation.<br><br>CONCLUSIONS: Switching to aflibercept 8&#x2009;mg led to stable vision, significant anatomical improvements, extended treatment intervals and a favourable short-term safety profile. Longer follow-up is warranted.},
}
@article {pmid40920945,
year = {2025},
author = {Raîche-Marcoux, G and Guérin, S and Boisselier, &#xc9;},
title = {[Cellular models of inflammation in the posterior segment of the eye: exploring pathogenic mechanisms].},
journal = {Medecine sciences : M/S},
volume = {41},
number = {8-9},
pages = {657-665},
doi = {10.1051/medsci/2025099},
pmid = {40920945},
issn = {1958-5381},
support = {RGPIN-2022-03958//Conseil de recherches en sciences naturelles et en g&#xe9;nie du Canada (CRSNG)/ ; PJT-173366//Instituts de recherche en sant&#xe9; du Canada (IRSC)/ ; },
mesh = {Humans ; *Inflammation/pathology/etiology ; Animals ; *Models, Biological ; *Posterior Eye Segment/pathology ; Coculture Techniques ; Glaucoma/pathology ; },
abstract = {Glaucoma, age-related macular degeneration, and diabetic retinopathy are complex eye diseases that involve inflammation. Several cellular models are developed to study inflammation mechanisms in the posterior segment of the eye. These models, are composed of cells of various origins (human or animal), derived from different tissues (retina, choroid, skin, and umbilical cord) and belonging to different cell types (epithelial, endothelial, vascular, and neuronal). Multiple culture techniques are employed to analyze specific inflammatory responses. Various experimental approaches are used to induce inflammation in these cellular models and identify underlying molecular mechanisms. This review highlights the diversity of cell models used to study posterior ocular inflammation. It emphasizes the use of primary cell cultures, established cell lines, and different co-culture approaches. The goal is to further increase our understanding of these diseases which affect millions of people worldwide.},
}
@article {pmid40920277,
year = {2025},
author = {Tanaka, M and Miyata, M and Hata, M and Ooto, S and Tamura, H and Kido, A and Ueda-Arakawa, N and Miyake, M and Takahashi, A and Muraoka, Y and Tsujikawa, A},
title = {Recurrence associated with 2-year visual acuity after subretinal tissue plasminogen activator for submacular hemorrhage in neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {40920277},
issn = {1613-2246},
support = {25K12870//Japan Society for the Promotion of Science/ ; },
abstract = {PURPOSE: To identify predictors of the 2-year best-corrected visual acuity (BCVA) after subretinal tissue plasminogen activator (tPA) injection for massive submacular hemorrhage (SMH) complicating neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: A prospective, observational study.<br><br>METHODS: This study included consecutive eyes with massive SMH and nAMD that underwent vitrectomy with subretinal tPA injection and follow-up for 2 years. We analyzed the&#xa0;correlation between the 2-year BCVA and other parameters, including baseline BCVA, SMH height, SMH size, and SMH recurrence.<br><br>RESULTS: This study analyzed 20 eyes of 20 patients (72.5 &#xb1; 7.2 years). Two years after surgery, the mean logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.72 (Snellen equivalent, 20/105) &#xb1; 0.40 at baseline to 0.80 (Snellen equivalent, 20/126) &#xb1; 0.92. The BCVA did not change significantly during the 2-year observation period (P = 0.39). Compared to baseline, the 2-year BCVA improved in 11 eyes (55%) and declined in 6 eyes (30%) by more than 0.30 logMAR, including all five eyes with recurrence. The 2-year BCVA was correlated only with recurrence (P < 0.001, &#x3b2; = 0.85).<br><br>CONCLUSIONS: This study suggests that recurrence was a robust determinant of poor 2-year BCVA after vitrectomy with subretinal tPA injection for SMH complicating nAMD and that subretinal tPA injection was effective in most cases, without recurrence. Our findings highlight the importance of establishing methods for preventing and controlling recurrence to maintain long-term BCVA.},
}
@article {pmid40920159,
year = {2025},
author = {Dotsenko, KR and Zolotarev, AV and Karlova, EV and Zamytskiy, EA and Zubkova, EY and Balandina, EV and Ilyasova, NY and Demin, NS and Ionov, AY},
title = {[Nanosecond retinal laser therapy: three years of practical experience].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {4},
pages = {60-65},
doi = {10.17116/oftalma202514104160},
pmid = {40920159},
issn = {0042-465X},
mesh = {Humans ; Male ; Visual Acuity ; Female ; Tomography, Optical Coherence/methods ; Aged ; Follow-Up Studies ; *Macular Degeneration/surgery/diagnosis/physiopathology ; Treatment Outcome ; *Retina/surgery/pathology ; Middle Aged ; *Laser Coagulation/methods ; },
abstract = {OBJECTIVE: This study evaluated the outcomes of a 36-month follow-up after treatment with the ELLEX 2RT nanosecond laser.<br><br>MATERIAL AND METHODS: The study included 72 patients divided into two groups. Group 1 received 2RT nanosecond laser therapy, while group 2 did not undergo laser treatment. Patients with early and intermediate stages of age-related macular degeneration (AMD) were enrolled. The exclusion criteria from the study were the presence of reticular pseudodrusen, drusenoid detachment (avascular pigment epithelial detachment) measuring >1000 &#x3bc;m, and areas of retinal pigment epithelium (RPE) atrophy detected by optical coherence tomography (OCT).<br><br>RESULTS: After treatment, visual acuity in group 1 did not change and remained stable at 0.99, while in group 2 there was a decrease in mean uncorrected visual acuity (UCVA) from 0.98 to 0.86. In addition, OCT findings in group 1 showed no progression in 96% (41 eyes) of cases. At the same time, in 2% (1 eye) of cases, there was a significant positive trend in relation to retinal anatomy according to OCT, and in 2% (1 eye) of cases, despite some negative dynamics in retinal anatomy, there was no decrease in vision. In contrast, the disease progressed to the wet form in 19% of group 2 patients after 36 months of follow-up. According to microperimetry, retinal sensitivity in the macular area and in 2RT foci in group 1 was stable or slightly improved. There was a trend toward improved fixation on microperimetry.<br><br>CONCLUSION: Results of the study show that after 2RT therapy the condition of the retina can stabilize or even improve, supporting the broader use of retinal laser stimulation using a nanosecond laser in patients with early forms of AMD to prevent the progression of the disease and its transition to the wet form.},
}
@article {pmid40920153,
year = {2025},
author = {Kozina, EV and Samoylov, AN and Aksenov, KD and Aksenova, LE},
title = {[Algorithm for predicting treatment outcomes in vascular pigment epithelial detachment in neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {4},
pages = {12-18},
doi = {10.17116/oftalma202514104112},
pmid = {40920153},
issn = {0042-465X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Detachment/diagnosis/etiology/drug therapy ; Algorithms ; Male ; Female ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; *Wet Macular Degeneration/complications/diagnosis/drug therapy ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Fluorescein Angiography/methods ; Intravitreal Injections ; },
abstract = {UNLABELLED: Automated analysis of optical coherence tomography (OCT) biomarkers improves the prediction of results of loading anti-VEGF therapy of vascular pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (nAMD).<br><br>OBJECTIVE: This study evaluated the effectiveness of OCT biomarker analysis algorithm in predicting the anatomical outcomes of loading anti-VEGF therapy for vascular PED in nAMD.<br><br>MATERIAL AND METHODS: OCT scans performed prior to loading anti-VEGF therapy were analyzed using the algorithm in 69 treatment-na&#xef;ve nAMD patients (70 eyes) with vascular PED exceeding 200 &#xb5;m in height. Qualitative biomarkers included subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective material beneath the PED, PED defects, and hyperreflective foci in the outer retinal layers. Quantitative parameters - height, width, and area of PED - were manually measured and segmented using a U-NET-based neural network.<br><br>RESULTS: The algorithm predicted flattening of higher (499.2&#xb1;198.1 &#x3bc;m) and wider (3205.6&#xb1;734.2 &#x3bc;m) PEDs containing large hyperreflective foci in the mid-retinal layers and defects in PED (n=35 eyes). Resistance to loading therapy was predicted in lower (430.1&#xb1;126.4 &#x3bc;m) and narrower (2824.1&#xb1;732.8 &#x3bc;m) PEDs with sub-PED hyperreflective material without IRF (n=31 eyes). Risk of retinal pigment epithelium (RPE) tear was predicted for PEDs higher than 600 &#x3bc;m (mean 587.4&#xb1;193.6 &#x3bc;m) in the presence of SRF but without PED defects (n=4 eyes). The automated OCT biomarker analysis algorithm effectively predicted resistance of PEDs with the lowest height, width, and area. Greater PED area and width were predictive of flattening, while PED height over 600 &#x3bc;m, calculated using the algorithm, was a predictor of RPE tear.<br><br>CONCLUSION: The developed OCT biomarker analysis algorithm enables effective prediction of anatomical outcomes following loading anti-VEGF therapy in vascular PED in nAMD.},
}
@article {pmid40919301,
year = {2025},
author = {Abou-Samra, A and Barazi, MD and Abbas, A and Sabbagh, O and Bade, Y and Do, BK and Du, J and Ebert, J and Fein, J and Levinson, JD and Melamud, A and Sabbagh, O and Ali, MH},
title = {Real-World Experience of Geographic Atrophy Treatment With Avacincaptad Pegol.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251367100},
pmid = {40919301},
issn = {2474-1272},
abstract = {Purpose:To present the first real-world safety data describing the clinical experience of geographic atrophy (GA) treatment with avacincaptad pegol in a large cohort. Methods: A retrospective, observational cohort study was conducted within the PRISM Vision Group by filtering for J codes for avacincaptad pegol from August 3, 2023, to October 10, 2024. Results: The study included 461 eyes of 335 patients with GA who were treated with intravitreal avacincaptad pegol 2 mg (0.1 mL of 20 mg/mL) injections. The mean follow-up time was 120 days. The mean injection interval was 52 days. Fourteen eyes (3%) developed an acute rise in intraocular pressure, and there were no reports of endophthalmitis, intraocular inflammation, or nonarteritic anterior ischemic optic neuropathy. Eight eyes (2.03%) converted to neovascular age-related macular degeneration, with an average of 2 injections before conversion and a predicted annualized rate of conversion of approximately 6.17%. One eye (0.2%) developed a vitreous hemorrhage. Conclusions: This study describes the real-world safety profile of avacincaptad pegol that may aid clinicians in understanding the risk of adverse events associated with this relatively new treatment for GA.},
}
@article {pmid40918516,
year = {2025},
author = {Zhou, H and Pang, J and Wu, B and Zhuang, Y and Li, S and Jiang, J},
title = {Dihydromyricetin attenuates age-related macular degeneration: pharmacological effects and exploration of putative targets.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1588970},
pmid = {40918516},
issn = {1663-9812},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, with limited effective treatments available. This study aimed to investigate the pharmacological effects of dihydromyricetin (DHM) on AMD and to identify its putative pharmacological targets through network analysis and molecular docking approaches.<br><br>METHODS: In vitro experiments established an AMD model using sodium iodate (SI)-induced ARPE-19 cells, with CCK-8 assays determining 15 mM SI as the optimal modeling concentration and 100 &#x3bc;M DHM as the optimal treatment concentration. For in vivo validation, an AMD model was generated in C57 mice via tail vein injection of SI (30 mg/kg). Subsequent oral gavage with DHM (50 or 100 mg/kg) was administered. Integrated network analysis, molecular docking, and RT- qPCR validation were employed.<br><br>RESULTS: RT-qPCR analysis revealed that DHM reversed SI-induced aberrant expression of AMD-associated biomarkers (ICAM-1, APOE, HTRA1, ABCA4). Light microscopy and flow cytometry demonstrated DHM's significant mitigation of SI-triggered cellular morphological alterations and apoptosis (35% reduction). Western blot analysis further confirmed DHM-mediated suppression of apoptosis through regulation of p53, Bax, cleaved caspase-3, and Bcl-2 expression. High-dose DHM significantly attenuated retinal thinning (10.7% reduction), decreased pigment loss, and ameliorated structural disorganization in the outer nuclear layer (ONL). These analyses predicted seven putative targets implicated in functional categories including neurodegeneration, apoptosis, and DNA modification. Subsequent PPI network construction and GO/KEGG enrichment analyses revealed these targets' involvement in biological processes such as angiogenesis and extracellular matrix organization.<br><br>CONCLUSION: In conclusion, the present study demonstrates that DHM can mitigate AMD-related damage in both in vitro and in vivo models, while predicting putative targets and signaling pathways through which DHM may exert its effects against AMD. These findings offer promising directions for the development of AMD therapies and lay the groundwork for further investigation into DHM as a candidate drug for treating and preventing AMD.},
}
@article {pmid40917264,
year = {2025},
author = {Lishinsky-Fischer, N and Cnaany, Y and Nitzan, I and Chowers, I and Levy, J},
title = {Longitudinal Assessment of Age-Related Macular Degeneration and Risk of Dementia Using Clinical Setting Data.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100891},
pmid = {40917264},
issn = {2666-9145},
abstract = {OBJECTIVE: To examine whether there is an association between age-related macular degeneration (AMD) and dementia using a large, multi-institutional clinical data.<br><br>DESIGN: A retrospective cohort study.<br><br>PARTICIPANTS: Patients with AMD, including both neovascular AMD (nvAMD) and non-neovascular AMD (non-nvAMD) types, along with matched controls who had a record of eye examination but no diagnosis of AMD.<br><br>METHODS: Data were extracted from the 3 largest TriNetX networks (Global, United States, and Europe, Middle East, and Africa [EMEA]). Dementia diagnoses (Alzheimer disease [AD], vascular dementia, and unspecified dementia) and dementia-related medication use were compared between AMD and non-AMD groups. Diagnoses were identified using International Classification of Diseases, 10th Revision codes. Survival analyses were performed using Kaplan-Meier curves, and hazard ratios (HRs) were estimated using Cox proportional hazards models across 5-, 7-, and 10-year follow-up periods.<br><br>MAIN OUTCOME MEASURES: Hazard ratios for dementia subtypes in AMD patients versus non-AMD patients and in nvAMD patients versus non-nvAMD patients.<br><br>RESULTS: No significant association between AMD and AD was observed in the global network. In the United States, AMD was associated with a reduced risk of AD at 5 and 7 years (HR = 0.79 and 0.75; P < 0.0001), but not at 10 years. In the EMEA cohort, a protective association emerged at 7 and 10 years (HR = 0.16 and 0.33; P = 0.0063 and 0.0265). Vascular dementia showed no global association but was reduced in the United States at 5 and 7 years (HR = 0.73 and 0.79; P < 0.0001 and 0.0003). Unspecified dementia was associated with increased risk globally (HR = 1.17-1.27; P &#x2264; 0.0016), while the US data indicated a protective trend at 5 and 7 years. Dementia medication use was elevated in the global network at 7 years (HR = 1.27, P < 0.0001), but lower in the United States across all time points (P < 0.01). The negative control outcome (appendicitis) showed no difference between groups. No significant differences in AD or vascular dementia were found between nvAMD and non-AMD patients, although unspecified dementia and dementia medication use were lower in the nvAMD group.<br><br>CONCLUSIONS: Age-related macular degeneration was not consistently positively associated with AD or vascular dementia across networks. Regional variation, particularly negative associations in the United States, suggests underlying health care or diagnostic differences.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40915520,
year = {2025},
author = {Shen, M and Berni, A and Liu, J and Hiya, F and Herrera, G and El-Mulki, OS and Beqiri, S and Cheng, Y and Kastner, J and Trivizki, O and Kumar, S and Zhang, Y and Le, VH and O'Brien, RC and Nicola, MD and Yehoshua, Z and Dubovy, SR and Wang, RK and Gregori, G and Rosenfeld, PJ},
title = {Real-World Experience With Intravitreal Pegcetacoplan for the Treatment of Geographic Atrophy in Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {281},
number = {},
pages = {31-41},
doi = {10.1016/j.ajo.2025.09.006},
pmid = {40915520},
issn = {1879-1891},
abstract = {PURPOSE: To report on the real-world experience of using intravitreal pegcetacoplan for the treatment of geographic atrophy (GA) in age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective interventional case series.<br><br>METHODS: Eyes with symptomatic GA secondary to AMD were treated with 15 mg of intravitreal pegcetacoplan and participated in an ongoing prospective swept-source optical coherence tomography angiography (SS-OCTA) imaging study. All eyes underwent SS-OCTA imaging before and during pegcetacoplan therapy to assess for GA lesion size, the presence of nonexudative macular neovascularization (MNV), and the onset of exudation. The growth rate of GA and best-corrected visual acuity (BCVA) were assessed for eyes followed for 1 year.<br><br>RESULTS: From April 12, 2023, to November 11, 2024, 154 eyes were injected with pegcetacoplan, and 103 eyes had 1-year follow-up. At baseline, 11 eyes had been previously treated with anti-VEGF therapy, and 9 eyes were diagnosed with treatment-na&#xef;ve nonexudative MNV by SS-OCTA. Each eye received an average of 10 &#xb1; 2 injections, with an average interval of 1.2 months between injections. For the 97 eyes with 1 year of follow-up and measurable GA, the square-root (sqrt) GA growth rate after pegcetacoplan treatment was 0.24 &#xb1; 0.15 mm/year. Of these 97 eyes, 63 eyes had prior annual visits before pegcetacoplan treatment was started. In these eyes, the annual sqrt GA growth rate was 0.33 &#xb1; 0.22 mm/year before pegcetacoplan and 0.21 &#xb1; 0.12 mm/year after pegcetacoplan, resulting in a 37% decrease in the growth rate (P < .001). There were no significant differences in GA growth rate between foveal and nonfoveal GA, either before or after the use of pegcetacoplan (all P &#x2265; .80). The mean BCVA declined from 63 &#xb1; 14 to 59 &#xb1; 15 letters over 1 year (P = .001), with no significant difference between foveal and nonfoveal GA (P = .36). Among the 29 eyes developing exudation during pegcetacoplan treatment, 19 (66%) had no evidence of any detectable MNV at baseline and during treatment on SS-OCTA.<br><br>CONCLUSIONS: Eyes treated with pegcetacoplan after 1 year had a 37% reduction in GA growth rate compared with their prior annual growth rate. Pegcetacoplan slowed the growth for foveal and nonfoveal GA at a similar rate. Most of the pegcetacoplan-associated exudation was not due to detectable MNV.},
}
@article {pmid40915427,
year = {2026},
author = {Loh, NC and Rojas-Carabali, W and Lim, YH and Bong, JE and Villabona-Martinez, V and Cifuentes-González, C and Kumar, M and Sadda, S and Schmetterer, L and Cheung, CMG and Gupta, V and Grewal, DS and Fekrat, S and de-la-Torre, A and Lee, B and Wei, X and Nivison-Smith, L and Agrawal, R},
title = {Choroidal vascularity index as a marker of health and disease: systematic review and meta-analyses.},
journal = {Survey of ophthalmology},
volume = {71},
number = {1},
pages = {35-52},
doi = {10.1016/j.survophthal.2025.09.003},
pmid = {40915427},
issn = {1879-3304},
mesh = {Female ; Humans ; Pregnancy ; Biomarkers ; *Choroid/blood supply ; *Tomography, Optical Coherence/methods ; },
abstract = {The Choroidal Vascularity Index (CVI), derived from optical coherence tomography (OCT), has emerged as a potential biomarker for detecting vascular changes. Understanding its variability across physiological states, ocular conditions, and systemic diseases is crucial for its integration into clinical practice. We evaluated variations in CVI across different physiological states (e.g., first-trimester pregnancy), ocular conditions (e.g., age-related macular degeneration[AMD]), and systemic diseases (e.g., diabetes mellitus) compared to healthy controls. From 1210 identified articles, 63 studies (7316 participants: 4000 controls and 3316 cases) met inclusion criteria. Data covered 12 distinct conditions and physiological states. Most studies were conducted in Europe and Asia, predominantly using spectral-domain OCT machines with a low risk of bias. Increased CVI was seen in some physiological states (e.g., Valsalva maneuver, first-trimester pregnancy) and some disorders (e.g. active panuveitis, inactive thyroid eye disease). Reduced CVI was found in diabetes mellitus (both with or without diabetic retinopathy), hyperopic amblyopia, and AMD. CVI demonstrates potential as a biomarker to differentiate between physiological states and pathological conditions compared to healthy controls. These findings underscore the choroid's adaptive response to systemic and ocular challenges, highlighting CVI's relevance in understanding disease mechanisms and monitoring health.},
}
@article {pmid40914928,
year = {2025},
author = {Liu, H and Ouyang, Y and Ge, H},
title = {SIRT1 as a potential target for age-related eye diseases: mechanisms and therapeutic strategies.},
journal = {Human cell},
volume = {38},
number = {6},
pages = {155},
pmid = {40914928},
issn = {1749-0774},
support = {2023HX015//Heilongjiang Charity Federation of China/ ; 2022HX005//Harbin Charity Federation/ ; },
mesh = {*Sirtuin 1/genetics/physiology/metabolism ; Humans ; *Eye Diseases/therapy/genetics ; Oxidative Stress/genetics ; *Aging/genetics ; Apoptosis/genetics ; *Molecular Targeted Therapy ; Diabetic Retinopathy/genetics/therapy ; Macular Degeneration/genetics/therapy ; Autophagy/genetics ; Cataract/genetics/therapy ; Cellular Senescence/genetics ; Glaucoma/genetics/therapy ; Inflammation ; Dry Eye Syndromes/genetics/therapy ; },
abstract = {Age-related eye diseases (AREDs) are the leading cause of visual impairment in the elderly, affecting the structure of the anterior and posterior segments of the eye, significantly reducing the quality of life of patients, and even leading to irreversible blindness. Typical AREDs include age-related cataract (ARC), dry eye disease (DED), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), the global prevalence of which continues to rise, becoming a serious public health concern. SIRT1 is an NAD + dependent deacetylase, which plays an important physiological regulatory role in ocular tissues, mainly affecting gene expression and various cellular processes by regulating the acetylation status of substrate proteins. Studies have shown that SIRT1 plays a key role in oxidative stress, inflammation, autophagy, apoptosis and metabolism, and its expression or activity decreases can accelerate cell senescence and promote the occurrence and development of AREDs. In addition, SIRT1 expression levels and changes in its activity have been shown to be strongly associated with AREDs, making it a potential target for disease intervention and therapy. Therefore, this review systematically summarizes the biological role and regulatory mechanism of SIRT1 in AREDs, and explored its potential value as a therapeutic target, providing theoretical basis for future drug development and clinical transformation.},
}
@article {pmid40914442,
year = {2026},
author = {Song, W and Chen, W and Chi, J and Liu, X and Zhu, W},
title = {The role of lipid metabolism disorder in the progression and treatment of ocular vascular diseases.},
journal = {Survey of ophthalmology},
volume = {71},
number = {1},
pages = {1-13},
doi = {10.1016/j.survophthal.2025.09.002},
pmid = {40914442},
issn = {1879-3304},
mesh = {Humans ; *Lipid Metabolism/physiology ; Disease Progression ; *Lipid Metabolism Disorders/complications/physiopathology/metabolism ; Diabetic Retinopathy/metabolism ; *Retinal Diseases/metabolism ; Macular Degeneration/metabolism ; },
abstract = {Lipid metabolism plays a critical role in maintaining normal physiological functions and is strongly linked to the pathogenesis of ocular vascular diseases. We examine how disorders of lipid metabolism drive progression in ocular vascular diseases, including diabetic retinopathy, age-related macular degeneration, retinal vascular occlusive diseases, and retinopathy of prematurity. These disorders are classified as a related group due to their common feature of impaired ocular vascularization. Glaucoma has also been increasingly recognized as a condition resulting from both retinal and choroidal blood flow abnormalities, with shared lipid metabolism disturbances contributing to its pathogenesis. Lipid components such as fatty acids may exacerbate retinal and choroidal damage by promoting neovascularization and inflammatory responses. Additionally, lipid metabolic dysregulation negatively influences the retinal and choroidal microenvironment by increasing oxidative stress and inhibiting autophagy. We also discuss emerging therapeutic strategies targeting lipid metabolism, highlighting their potential in preventing or mitigating ocular vascular diseases. These include lipid-modulating agents and their use in combination with established therapies. Understanding the influence of lipid metabolism on the pathophysiology of these diseases could pave the way for the development of novel treatment approaches. These advancements hold potential to improve visual prognosis in patients with ocular vascular diseases. Identifying the specific roles and molecular targets associated with lipid metabolism in ocular vascular diseases will offer valuable insights into disease mechanisms. This knowledge will lay the groundwork for personalized and more effective clinical interventions.},
}
@article {pmid40913076,
year = {2025},
author = {Tsai, HR and Chang, WC and Lee, YC},
title = {Association between atrial fibrillation and age-related macular degeneration: A nationwide cohort study.},
journal = {Eye (London, England)},
volume = {39},
number = {15},
pages = {2800-2807},
pmid = {40913076},
issn = {1476-5454},
support = {TCMF-P 112-07//Buddhist Tzu Chi Medical Foundation/ ; },
mesh = {Humans ; *Atrial Fibrillation/epidemiology/complications ; Male ; Female ; Taiwan/epidemiology ; Aged ; Retrospective Studies ; Incidence ; *Macular Degeneration/epidemiology ; Middle Aged ; Risk Factors ; Aged, 80 and over ; Databases, Factual ; Proportional Hazards Models ; },
abstract = {BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) and age-related macular degeneration (AMD) are common debilitating conditions that share pathomechanisms involving chronic inflammation and oxidative stress. However, the association between AMD and AF, which is important for comprehending the pathogenesis, referral, and treatment strategies of these diseases, remains unknown.<br><br>SUBJECTS/METHODS: This nationwide population-based retrospective cohort study used claims data from the National Health Insurance Research Database of Taiwan. From 1 January 2003 to 31 December 2018, an AF and AMD cohort of 34,236 and 31,766 patients, respectively, along with their matched control cohorts, were constructed using stabilised inverse probability of treatment weighting. The primary outcomes were the incidence of AMD following newly diagnosed AF and the incidence of AF following newly diagnosed AMD. A Cox regression model was used to estimate hazard ratios (HR) for these outcomes. Subgroup analysis based on AMD subtype and stratified analyses by age and sex were also conducted.<br><br>RESULTS: Compared with controls, patients with AF had a significantly increased risk of developing AMD (HR 1.10; 95% confidence interval [CI] 1.04-1.17). Similarly, patients with AMD had a significantly increased risk of developing AF (HR 1.08; 95%CI 1.02-1.15). Further subgroup analysis revealed a reciprocal association between AF and dry AMD. Age- and sex-stratified analyses demonstrated increasing risk trends for AF and AMD.<br><br>CONCLUSIONS: AF and AMD may share common underlying risk factors and pathophysiological mechanisms. Our findings identified a reciprocal association between AF and AMD. Further research is warranted to elucidate the pathophysiology of AF and AMD.},
}
@article {pmid40911453,
year = {2025},
author = {Chen, X and Chan, W and Meng, Y and Liu, R and Yu, Y and Hu, S and Han, J and Wang, X and Zhou, J and Qiu, B and Wang, Y},
title = {Multi-Channel Temporal Interference Retinal Stimulation Based on Reinforcement Learning.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2025.3605434},
pmid = {40911453},
issn = {2168-2208},
abstract = {Retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa cause severe vision impairment, while current electrical stimulation therapies are limited by poor spatial targeting precision. As a promising non-invasive alternative, the efficacy of temporal interference stimulation (TIS) for retinal targeting depends on optimized multi-electrode parameters. This study reconstructed a whole-head finite element model with detailed ocular structures and applied reinforcement learning (RL)-based multi-channel electrode parameter optimization to retinal stimulation. Systematic evaluation demonstrated that the focal precision of TIS improves with increasing channel numbers (consistent across all subject head models), with RL significantly outperforming conventional genetic algorithms (GA) and unsupervised neural networks (USNN) in focusing capability. Furthermore, by implementing the computationally intensive envelope calculation using the JAX framework, we achieved a nearly order-of-magnitude reduction in optimization time (to approx. 2 minutes per run on an RTX 4090D), significantly enhancing the practical feasibility of the proposed RL framework. This work provides a novel and computationally efficient methodology for precise non-invasive neuromodulation parameter optimization, applicable not only to retinal diseases but potentially to broader neurological conditions.},
}
@article {pmid40909980,
year = {2025},
author = {Lin, T and Luo, S and Zhuang, C and Xiao, H and Ding, X and Li, S},
title = {Caregiver Burden Among Patients Receiving Anti-VEGF Intravitreal Injections for AMD and DR: A Cross-Sectional Study in Guangzhou.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3071-3078},
pmid = {40909980},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the caregiver burden and its associated factors among patients receiving anti-VEGF intravitreal injections for age-related macular degeneration (AMD) and diabetic retinopathy (DR) in a tertiary hospital in Guangzhou, China.<br><br>METHODS: This cross-sectional study recruited 88 patients who received intravitreal anti-VEGF injections and their primary caregivers. Patients completed the Activities of Daily Living (ADL) scale, while caregivers completed the Zarit Burden Interview (ZBI) and the Connor-Davidson Resilience Scale (CD-RISC). One-way ANOVA and Pearson correlation analysis were conducted to assess the associations between patient function, caregiver burden, and related sociodemographic factors.<br><br>RESULTS: The mean ADL score of patients was 18.99 &#xb1; 8.34, while the mean caregiver burden score was 18.22 &#xb1; 18.04. A significant positive correlation was found between the patient's ADL score and caregiver burden (r = 0.405, p < 0.01). Caregivers who were employed part-time or not cohabiting with patients reported significantly higher burden scores (p = 0.034 and p = 0.03, respectively). Additionally, the caregiver burden among DR patients was higher than among AMD patients (p = 0.026).<br><br>CONCLUSION: Significant caregiver burden exists among those assisting patients receiving intravitreal injections, especially for DR patients and those with reduced ADL function. Caregiver availability and living arrangements should be considered in the design of follow-up schedules to improve treatment adherence and outcomes.},
}
@article {pmid40909979,
year = {2025},
author = {Morse, AR and Hark, LA and Seiple, WH and Gorroochurn, P and Tang, H and Rojas, R and Chen, R and Horowitz, JD and Bearelly, S and Diaconita, V and Shukla, AG and Wang, Y and Maruri, SC and Torres, DR and Cioffi, GA and Chang, S and Tezel, T},
title = {Association of Behavioral Factors with Activation in Patients with Age-Related Macular Degeneration or Diabetic Retinopathy.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3059-3069},
pmid = {40909979},
issn = {1177-5467},
abstract = {INTRODUCTION: Activation is the degree that individuals have the knowledge, skills, beliefs, and behaviors necessary for effective health-care self-management. Those with higher activation are more likely to engage in behaviors associated with improved care outcomes, including increased medication and appointment adherence. Identifying and addressing patients' activation levels and associated behaviors at the outset of care can help to develop interventions to improve patients' participation in their healthcare. Our objective was to study the association of psychosocial factors with activation to identify behavioral factors that could increase activation.<br><br>METHODS: Individuals with bilateral AMD or DR (n = 1146) were identified from electronic medical records at a single academic medical center. Randomly selected potential participants (n = 682) were sent a letter inviting their participation. Consenting participants (AMD n = 161; DR n = 94) were administered the Patient Activation Measure (PAM), the National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ), Multidimensional Health Locus of Control - form C (MHLC), Perceived Medical Condition Self-Management Scale (PMCSMS), Patient Health Questionnaire-9 (PHQ-9), a measure of health literacy and a sociodemographic health questionnaire by phone.<br><br>RESULTS: In multivariable analysis of participants with AMD, for each unit increase in MHLC Internal score, mean PAM score increased by 0.50 (P = 0.001).&#xa0;In multivariable analysis of participants with DR, for each unit increase in MHLC Chance, mean PAM score decreased by 0.48 (P = 0.0391). Differences on MHLC Internal and Chance scores among and between those with dry or wet AMD and non-proliferative or proliferative DR were all significant (P < 0.001).<br><br>DISCUSSION: In this cross-sectional cohort study of 255 participants with bilateral diabetic retinopathy or age-related macular degeneration, higher internal LOC and lower external LOC were associated with higher activation scores. Interventions that increase patient activation may increase internal LOC and reduce external LOC, improving patients' participation in their care, and improve health-care outcomes.},
}
@article {pmid40909754,
year = {2025},
author = {Ozaki, A and Kawai, A and Akiba, R and Okayama, S and Ohno, N and Kajita, K and Masuda, T and Yokota, S and Ito, SI and Peiyan, D and Onoue, K and Yonemura, S and Kondo, M and Kurimoto, Y and Fu, Y and Mandai, M},
title = {Genome-edited retinal organoids restore host bipolar connectivity in the primate macula.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909754},
issn = {2692-8205},
support = {U24 EY033272/EY/NEI NIH HHS/United States ; },
abstract = {Retinal organoids (ROs) represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but whether host cone bipolar cells (BCs) in the primate macula can rewire with transplanted photoreceptors remains unresolved. Here, we transplanted genome-edited human retinal organoids lacking ON-BCs (Islet-1 [-]/[-] ROs) into a non-human primate macular degeneration model. Remarkably, host rod and cone BCs extended dendrites toward grafted photoreceptors, forming functional synapses confirmed by immunohistochemistry, ultrastructural imaging, and focal macular electroretinography. Both ON- and OFF-pathway connectivity was rebuilt, providing the first demonstration of host-graft synaptic integration in the primate macula. These results establish that primate cone circuits retain a surprising capacity for rewiring and highlight genome-edited ROs as a powerful platform for vision restoration. Our findings represent a critical translational step toward stem cell-based therapies capable of repairing central vision in patients with advanced macular degeneration.},
}
@article {pmid40908402,
year = {2025},
author = {Holmes, C and Kazantzis, D and Raza, SA and Wijesingha, N and Taylor, TR and Hagag, A and Riedl, S and Mai, J and Rueckert, D and Bogunović, H and Scholl, H and Schmidt-Erfurth, U and Fritsche, L and Lotery, A and Sivaprasad, S},
title = {Using adaptive optics to assess hyporeflective clump speed and size in age-related macular degeneration in the PINNACLE Study. (PINNACLE Study Report 6).},
journal = {Eye (London, England)},
volume = {39},
number = {15},
pages = {2793-2799},
pmid = {40908402},
issn = {1476-5454},
support = {/WT_/Wellcome Trust/United Kingdom ; 210572/Z/18/Z//Wellcome Trust (Wellcome)/ ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Ophthalmoscopy/methods ; Aged ; *Retinal Pigment Epithelium/pathology ; Female ; Male ; *Macular Degeneration/diagnosis ; Aged, 80 and over ; Middle Aged ; Geographic Atrophy ; },
abstract = {BACKGROUND/OBJECTIVES: Hyporeflective clumps (HRC) are a common finding in adaptive optics ophthalmoscopy (AOO) of age-related macular degeneration (AMD). They appear on optical coherence tomography (OCT) as hyperreflective foci (HRF) or abutting the retinal pigment epithelium (RPE) layer as RPE thickening. The cellular origin of HRF is debated between migrated RPE cells and mononuclear phagocytes (MP). Microglial cells are MP known to migrate at 0.02 µm/s, but RPE migration speed is unknown. Phenotyping HRCs by migration speed and size may improve our understanding of HRFs.<br><br>METHODS: Patients with non-neovascular AMD were imaged with the RTX1 retinal camera (Imagine Eyes, Orsey, France). Pairs of AOO images taken 1-3&#x2009;h apart were centred on areas with multiple HRCs and compared to identify mobile HRCs. Macular OCT scans were performed immediately after initial AOO.<br><br>RESULTS: A total of 21 pairs of images from 14 eyes of 12 patients were of adequate quality to assess HRCs. There were 411 measurable HRCs, with a mean diameter of 15.9&#x2009;&#xb1;&#x2009;6.0&#x2009;&#xb5;m. The HRCs were larger in images of atrophy (p&#x2009;<&#x2009;0.001). Within the timeframe assessed, most HRCs remained static, but mobile HRCs were not uncommon and migrated up to 0.015&#x2009;&#xb5;m/s. HRFs on OCT corresponding to mobile HRCs on AOO appeared adjacent to the RPE or in the interdigitation zone.<br><br>CONCLUSION: AOO can detect HRC movement in AMD in images captured a mean of 105.5&#x2009;min apart. HRC size and movement speed are consistent with microglial cells, but may also represent RPE cells. HRCs appear larger in images of atrophy.},
}
@article {pmid40908046,
year = {2025},
author = {Yu, J and Zhang, Y and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association of leucocyte telomere length with incident age-related macular degeneration: a prospective UK Biobank Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327492},
pmid = {40908046},
issn = {1468-2079},
abstract = {PURPOSE: There have been conflicting findings on the role of leucocyte telomere length (LTL) in the risk of age-related macular degeneration (AMD). In this study, we evaluated the associations between LTL and the risk of incident AMD and explored whether age, sex and/or genetic predisposition to AMD can modify these associations.<br><br>METHODS: We conducted a longitudinal cohort study involving 332&#x2009;123 AMD-free participants with complete baseline covariates and LTL data from the UK Biobank. We employed multivariable Cox proportional hazards models to test the association between LTL and AMD incidence, estimating the HRs and 95% CIs. Genetic risk was assessed using polygenic risk score (PRS).<br><br>RESULTS: During a median follow-up of 13.63 years, 6754 participants (2.03%) developed AMD. Shorter LTL was not associated with incident AMD risk (HR=1.042, 95%&#x2009;CI: 0.992 to 1.094; p=0.10) after adjusting for multiple confounders. Sex showed an interactive effect with LTL (p=0.01 for interaction) on incident AMD risk, while age and PRS did not modify these associations. We identified a significant association between shorter LTL and incident AMD risk in females (HR=1.093, 95%&#x2009;CI: 1.025 to 1.166; p=0.007), but not in males. Moreover, shorter LTL was associated with thinner photoreceptor segments only in females at both baseline and repeated assessments (&#x3b2;=-0.141&#x2009;&#xb5;m, 95%&#x2009;CI: -0.267 to -0.016; &#x3b2;=-0.345&#x2009;&#xb5;m, 95%&#x2009;CI: -0.649 to -0.041, p<0.05).<br><br>CONCLUSIONS: Shorter LTL increased the risk of incident AMD in females, suggesting LTL as a potential biomarker for AMD development with sex-specific function.},
}
@article {pmid40907629,
year = {2025},
author = {Ng, PQ and Huang, K and McLellan, FC and Yang, M and Lennikov, A and Hu, Z and Chaudhary, S and Appiah, AC and Vuong, ML and Shu, DY},
title = {Dimethyl fumarate is an inhibitor of pathological angiogenesis.},
journal = {Cellular signalling},
volume = {136},
number = {},
pages = {112106},
doi = {10.1016/j.cellsig.2025.112106},
pmid = {40907629},
issn = {1873-3913},
mesh = {*Dimethyl Fumarate/pharmacology/therapeutic use ; Animals ; Humans ; Mice ; Endothelial Cells/drug effects/metabolism ; *Neovascularization, Pathologic/drug therapy/pathology ; Vascular Endothelial Growth Factor A/metabolism ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; *Angiogenesis Inhibitors/pharmacology ; Mice, Inbred C57BL ; Choroid/drug effects ; },
abstract = {Vascular endothelial growth factor (VEGF), a pro-angiogenic molecule, supports blood vessel growth during wound healing but also drives pathological neovascularization in blinding eye diseases such as neovascular age-related macular degeneration (nAMD). Dimethyl fumarate (DMFu), an FDA-approved drug for multiple sclerosis, has shown promising anti-inflammatory properties in the retinal pigment epithelium, a crucial structure disrupted in nAMD. Here, we extend the therapeutic potential of DMFu by discerning the anti-angiogenic capabilities of DMFu in choroidal and retinal endothelial cells. Choroidal endothelial cell proliferation was significantly attenuated by DMFu in the mouse choroidal sprouting assay. Even in the presence of VEGF, DMFu disrupted cell migration and tube formation in human microvascular retinal endothelial cells (HRECs). Bulk RNA sequencing highlighted that DMFu successfully ameliorated the expression of VEGF-controlled gene expression. Weighted gene co-expression network and gene set enrichment analyses confirmed downregulation of pathways involved in branching blood vessel morphogenesis but also revealed novel transcriptional mechanisms of action, including control of microtubule transport and ATP synthesis coupled electron transport. DMFu induced a decrease in maximal mitochondrial respiration, an increase in glycolysis and glycolytic capacity and reduced Complex II protein expression of the SDHB subunit on western blot. Such metabolic rewiring may limit the bioenergetic demands required to support angiogenic growth. With therapies available for nAMD being both limited and invasive, DMFu is a contender to be rapidly repurposed as an oral, patient-friendly therapeutic alternative.},
}
@article {pmid40906190,
year = {2025},
author = {Mansour, AM and Gad, MS and Habib, S and Elmasry, K},
title = {Bidirectional Hypoxic Extracellular Vesicle Signaling Between Müller Glia and Retinal Pigment Epithelium Regulates Retinal Metabolism and Barrier Function.},
journal = {Biology},
volume = {14},
number = {8},
pages = {},
pmid = {40906190},
issn = {2079-7737},
support = {P30EY031631//This work is supported by the Start-up fund from Augusta University, the Dental College of Georgia for KE and NIH core grant P30EY031631 to Vision Discovery Institute at Medical Col-lege of Georgia, Augusta University, Augusta, GA, USA./ ; },
abstract = {The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood-retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles' (EVs') signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood-retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies.},
}
@article {pmid40905748,
year = {2025},
author = {Miller, A and Crossland, MD and Macnaughton, J and Latham, K},
title = {The Usefulness of a Wearable Electronic Vision Enhancement System for People With Age-Related Macular Degeneration: A Randomized Crossover Trial.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {9},
pages = {8},
pmid = {40905748},
issn = {2164-2591},
mesh = {Humans ; Female ; *Macular Degeneration/rehabilitation/physiopathology ; Male ; Cross-Over Studies ; *Wearable Electronic Devices ; Quality of Life ; Aged, 80 and over ; Aged ; Visual Acuity/physiology ; *Vision, Low/rehabilitation ; *Sensory Aids ; Middle Aged ; },
abstract = {PURPOSE: To determine the usefulness of a wearable electronic vision enhancement system (wEVES) for people with age-related macular degeneration (AMD).<br><br>METHODS: Thirty-four adults with AMD, 64.7% female, mean age 80.2(&#xb1;6.0), were recruited from a UK low vision service. A 12-week non-masked randomized crossover trial compared wEVES usefulness with participants' existing low vision solutions. Primary outcome measures were visual ability, vision-related quality of life (VRQoL), device usage, and user-reported preferred device. Secondary outcomes were adverse effects, willingness to purchase, and qualitative reactions.<br><br>RESULTS: Overall visual ability improved with wEVES compared to existing solutions alone (mean difference -0.26; 95% confidence interval [CI], -0.48 to -0.04; P = 0.02). The wEVES were used for varied activities, including distance tasks, with few reported alternative strategies. However, these findings did not translate into changes in VRQoL (mean difference 0.10; 95% CI, -0.27 to 0.46; P = 0.59) or sustained device use. The wEVES were not the most preferred device for any task or individual, even when self-reported performance surpassed existing solutions. Adverse effects were minor, but participants' satisfaction and willingness to use wEVES declined significantly from trial baseline to end.<br><br>CONCLUSIONS: The wEVES improved self-reported visual ability, indicating their potential to support vision rehabilitation for people with AMD, albeit in a device that was largely not preferred over existing solutions. A user-led home trial evaluated using mixed methods is more indicative of the usefulness of wEVES for people with AMD than a short clinical demonstration.<br><br>TRANSLATIONAL RELEVANCE: To understand the usefulness of wEVES for people with AMD, broader measures than visual function and visual ability should be applied within longer user-led assessments.},
}
@article {pmid40905027,
year = {2025},
author = {},
title = {Erratum: Determinants of Healthcare Professionals' Knowledge on Age-Related Macular Degeneration Risk Factors in Ethiopia [Corrigendum].},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {3009-3010},
doi = {10.2147/OPTH.S562800},
pmid = {40905027},
issn = {1177-5467},
abstract = {[This corrects the article DOI: 10.2147/OPTH.S514480.].},
}
@article {pmid40904726,
year = {2025},
author = {Cheng, S and Chen, Z and Peng, F and Deng, P and Wang, M and Liu, S and Du, Y and Zuo, G},
title = {Exploration Progress on Inflammatory Responses and Immune Regulatory Mechanisms in Diabetic Retinopathy.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {11895-11909},
pmid = {40904726},
issn = {1178-7031},
abstract = {Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. In recent years, with the number of diabetic patients increasing annually, the number of DR patients has also been rising, and it has become one of the major blinding eye diseases worldwide. The pathogenesis of DR has not been fully clarified but includes microvascular lesions and metabolic factors. However, with the continuous exploration of the pathogenesis of DR, immune system disorders and inflammation have also been found to be important pathogenic mechanisms of DR and research on inflammation and immune mechanisms in DR have received increasing attention. This article reviews aspects such as the activation of inflammatory cells, the expression of inflammatory factors, and the complement system and explores the important roles of inflammation and immune mechanisms in the pathogenesis of DR, providing a theoretical basis for a deeper understanding of DR and potential explorations of new therapeutic strategies for DR.},
}
@article {pmid40902824,
year = {2025},
author = {Parmar, UPS and Arora, A and Agarwal, A and Gangaputra, S and Agrawal, R and Gupta, V},
title = {Detection and quantification of fluorescein angiography leakage: From manual grading to advances in machine learning.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.08.015},
pmid = {40902824},
issn = {1879-3304},
abstract = {Fluorescein angiography (FA) has long been a cornerstone for evaluating retinal vascular leakage in diseases like uveitis, diabetic retinopathy, and macular degeneration, but its interpretation relies on subjective grading that can vary between clinicians. With the emergence of artificial intelligence (AI), there is a push to transform this qualitative assessment into objective, quantifiable metrics. We conducted a comprehensive literature search using PubMed, Embase, and Scopus, combining keywords and MeSH terms related to fluorescein angiography leakage, artificial intelligence, and retinal vascular diseases. Studies were included if they assessed FA leakage using manual, semi-automated, or AI-based methods and were peer-reviewed, published in English, and focused on human subjects. Our review charts the evolution from manual grading to modern machine learning techniques that segment and measure leakage using various angiograms. These AI-based approaches enable standardized, reproducible leakage indices that correlate with disease severity, inform treatment decisions, stratify high-risk patients, and facilitate sensitive monitoring of therapeutic response. We also introduce the concept of "minimal residual disease" in this context. By moving from coarse, subjective estimations to precise digital biomarkers, AI-driven FA leakage quantification promises to improve clinical care and research endpoints in retinal disease.},
}
@article {pmid40902799,
year = {2025},
author = {Lakhani, M and Kwan, ATH and Kundapur, D and Popovic, MM and Damji, KF and Hurley, BR},
title = {Association of Anti-VEGF Therapy with Reported Ocular Adverse Events: A Global Pharmacovigilance Analysis.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.08.018},
pmid = {40902799},
issn = {2468-6530},
abstract = {OBJECTIVE: Anti-VEGF therapies have transformed the management of neovascular age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. This class-wide pharmacovigilance study evaluated the disproportionality of reported ocular adverse events (AEs) among anti-VEGF agents using postmarketing data.<br><br>DESIGN: A population-based, observational pharmacovigilance study.<br><br>PARTICIPANTS: Reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (January 2004-September 2024) for individuals treated with anti-VEGF agents.<br><br>METHODS: Ocular AEs were identified from FAERS, and disproportionality was assessed by comparing each anti-VEGF agent to background reporting using reporting odds ratios (RORs, 95% confidence interval [CI]); signals were considered significant if information component (IC025) > 0. Ranibizumab, aflibercept, brolucizumab, and faricimab were evaluated to compare ocular AE profiles among agents.<br><br>MAIN OUTCOME MEASURES: Disproportionality of reported ocular AEs among anti-VEGF agents.<br><br>RESULTS: Across included patients receiving anti-VEGF agents with ocular AEs, most were female and aged 65 to 85 years. When comparing intraocular inflammation (IOI) signals across anti-VEGF agents, the strongest association was observed with brolucizumab (ROR = 633.32), followed by faricimab (ROR = 156.44), aflibercept (ROR = 51.29), and ranibizumab (ROR = 16.90). Faricimab was notably associated with elevated disproportionality signals for reports of anterior segment inflammation, including anterior chamber flare (ROR = 270.95), unspecified anterior chamber inflammation (ROR = 226.28), iridocyclitis (ROR = 214.60), and iritis (ROR = 88.90). For posterior segment involvement, increased reporting of vitritis was observed with brolucizumab (ROR = 1769.33), faricimab (ROR = 466.99), aflibercept (ROR = 165.31), and ranibizumab (ROR = 56.67). Rare but clinically significant complications were reported across all agents, including for reports of endophthalmitis (aflibercept ROR = 208.88, ranibizumab ROR = 114.69, faricimab ROR = 99.75, and brolucizumab ROR = 56.15), noninfectious endophthalmitis (aflibercept, ROR = 846.11, 244.42 for brolucizumab, 65.45 for ranibizumab, and 59.08 for faricimab), and pseudoendophthalmitis, which showed the strongest signal with faricimab (ROR = 262.31; all 95% CI = 29.37-649.50, P < 0.0001, IC025 > 0). Faricimab also demonstrated increased reporting of retinal vascular inflammation but showed comparatively lower signals for noninflammatory occlusive events and other serious ocular complications relative to other anti-VEGF agents.<br><br>CONCLUSIONS: This global pharmacovigilance study revealed variability in ocular AE reporting across anti-VEGF agents. Brolucizumab showed the strongest signal for IOI, whereas aflibercept showed the highest signal for endophthalmitis. Continued postmarketing monitoring is warranted to define evolving safety profiles across anti-VEGF agents.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid40901439,
year = {2025},
author = {Wildan, A and Rachmawati, B and Kartasasmita, AS and Rahmi, FL and Maharani, and Istiadi, H and Syifarahmah, A and Nurdiansyah, I and Wulandari, NF and Salsabilah, S},
title = {Development of a BALB/c mice model for blue light retinal damage.},
journal = {Journal of advanced pharmaceutical technology &amp; research},
volume = {16},
number = {3},
pages = {139-143},
pmid = {40901439},
issn = {2231-4040},
abstract = {Blue light exposure can damage the retina, resulting in retinal atrophy and significant vision loss. Currently, no efficient animal models can observe retinal damage caused by blue light within a defined timeframe. Creating a BALB/c mouse model for blue light-induced retinal damage is expected to enhance research focused on the prevention and treatment of age-related macular degeneration. This study explores the potential effect of blue light exposure on the BALB/c mice model by analysing apoptosis and retinal degeneration. Anatomical Pathology Laboratory of Diponegoro University and The Integrated Research and Testing Laboratory of Gadjah Mada University. This study design was a posttest-only control group design. Ten five-week-old BALB/c mice were divided into two groups. The exposure group received 10,000 lux of blue light in the special cage for 2 weeks, 3 h daily. Caspase-3 expression was assessed through polymerase chain reaction testing, and retinal thickness was analyzed using hematoxylin and eosin staining. We used the Shapiro-Wilk test to evaluate data normality. Parametric t-tests and nonparametric Mann-Whitney tests were applied to compare groups, with P < 0.05 considered significant. The average whole retinal thickness of the exposed group was 152.812 ± 20.919 µm, while the control group was 214.948 ± 53.284 µm (P = 0.04). The average caspase-3 expression in the exposed group was 19.03 ± 8.57 µm, while the control group was 5.78 ± 2.63 µm (P = 0.011). This approach, utilizing animal models for blue light exposure, can be employed to learn about retinal damage caused by blue light.},
}
@article {pmid40900875,
year = {2025},
author = {Kaur, R and Morya, AK and Gupta, PC and Aggarwal, S and Menia, NK and Kaur, A and Kaur, S and Sinha, S},
title = {Artificial intelligence-based apps for screening and diagnosing diabetic retinopathy and common ocular disorders.},
journal = {World journal of methodology},
volume = {15},
number = {4},
pages = {107166},
pmid = {40900875},
issn = {2222-0682},
abstract = {Artificial intelligence (AI), encompassing machine learning and deep learning, is being extensively used in medical sciences. It is slated to positively impact the diagnosis and prognostication of various diseases. Deep learning, a subset of AI, has been instrumental in diagnosing diabetic retinopathy (DR), diabetic macular edema, glaucoma, age-related macular degeneration, and numerous other ocular diseases. AI performs equally well in the early prediction of glaucoma and age-related macular degeneration. Integrating AI with telemedicine promises to improve healthcare delivery, although challenges persist in implementing AI algorithms, especially in developing countries. This review provides a comprehensive summary of AI, its applications in ophthalmology, particularly DR, the diverse algorithms utilized for different ocular conditions, and prospects for the future integration of AI in eye care.},
}
@article {pmid40900080,
year = {2025},
author = {Yang, J and Bernardo-Colón, A and Becerra, SP},
title = {Lack of Pnpla2 Accelerates Progression of AMD-Like Features in Mice.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {12},
pages = {11},
pmid = {40900080},
issn = {1552-5783},
mesh = {Animals ; Mice ; *Macular Degeneration/metabolism/genetics/pathology/physiopathology ; *Retinal Pigment Epithelium/metabolism/pathology ; Electroretinography ; Disease Progression ; Disease Models, Animal ; *Lipase/genetics/physiology ; Cellular Senescence/physiology ; Mice, Inbred C57BL ; Mice, Knockout ; Tight Junctions/metabolism ; Zonula Occludens-1 Protein/metabolism ; Acyltransferases ; },
abstract = {PURPOSE: Lipid accumulation in the retinal pigment epithelium (RPE) contributes to cellular stress and progression of age-related macular degeneration (AMD). However, the regulation of lipid homeostasis in AMD development is not fully elucidated. The study investigates the effects of Pnpla2 deletion, a gene involved in lipid regulation, on key markers of RPE senescence and aging with potential relevance to AMD.<br><br>METHODS: RPE flat mounts and retinal cryosections were analyzed from Pnpla2-/- and Pnpla2+/+ mice aged 3 months. Senescence-associated &#x3b2;-galactosidase (SA-&#x3b2;-gal) activity was assessed in flat mounts. DAPI was used to quantify RPE cells with single or multiple nuclei. Immunohistofluorescence was carried out to assess RPE tight junctions and expression of senescence and AMD markers using antibodies to zonula occludens 1 (ZO-1), phospho-histone (P-&#x3b3;-H2AX), apolipoprotein E (ApoE), and high mobility group box 1 (HMGB1). Fundus imaging was acquired, and electroretinography (ERG) assessed visual function.<br><br>RESULTS: Pnpla2-/- RPE exhibited increased SA-&#x3b2;-gal activity, multinucleation of the population, and the translocation of HMGB1 from nucleus to cytoplasm, indicative of cellular senescence. Tight junctions were disrupted. The number of P-&#x3b3;-H2AX-positive RPE cells increased by 50%, suggesting increased DNA damage. ApoE levels were elevated in Bruch's membrane and subretinal regions. At 3 months of age, attenuation of ERG c-wave amplitude was observed in both Pnpla2-/- and Pnpla2+/- mice. By 7 months of age, Pnpla2+/- mice exhibited continued attenuation of ERG c-wave amplitude and developed white spots.<br><br>CONCLUSIONS: Pnpla2 deficiency accelerates cellular features of RPE aging and generates AMD-like features. These findings underscore the importance of PNPLA2 in mitigating AMD progression and highlight its significance in retinal health and degeneration.},
}
@article {pmid40896240,
year = {2025},
author = {Qian, T and Zhou, Y and Zhou, H and Wu, W and Yuan, Y and Yu, S and Xu, X},
title = {Intravitreal Double-Dose Conbercept Injection for the Treatment of Neovascular Age-Related Macular Degeneration: A Pilot Real-Life Clinical Practice Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {2965-2976},
pmid = {40896240},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the efficacy and safety of conbercept for neovascular age-related macular degeneration (nAMD) when administered at the labeled dose (0.5 mg) and double dose (1.0 mg).<br><br>METHODS: Patients with nAMD were randomized to either 1.0 mg or 0.5 mg groups. The 1.0 mg group received intravitreal injection of 1.0 mg conbercept once monthly for the first three months, followed by a pro re nata regimen (3+PRN). The 0.5 mg group received 3+PRN regimens of intravitreal 0.5 mg conbercept throughout the treatment period. Changes in best corrected visual acuity (BCVA), central macular thickness (CMT), and maximum pigment epithelial detachment (PED) height from baseline were compared between the two treatment groups at 1-, 3-, 6-, and 12-month follow-ups.<br><br>RESULTS: Thirty-three patients completed the study, including 16 in the 0.5 mg group with an average age of 74.00 &#xb1; 8.23 years, and 17 in the 1.0 mg group with an average age of 72.29 &#xb1; 6.47 years. At 3-month, BCVA improvement in the 1.0 mg group was significantly higher than in the 0.5 mg group (P = 0.0450), though no differences were observed at other time points. There was no statistical difference in CMT reduction at any follow-up points. Regarding PED height reduction, a significant difference was observed at the 1-month follow-up (P = 0.0345), but not at the 3-, 6-, or 12-month follow-ups. After drying the macula, the recurrence interval of fluid in the 1.0 mg group was significantly longer than in the 0.5 mg group (P = 0.0360). No related adverse event was reported in either group.<br><br>CONCLUSION: While the 1.0 mg group showed a transient but significant BCVA improvement at 3 months and a longer recurrence interval, further large-scale trials are needed to validate these preliminary findings.<br><br>TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR2000029503). Registration date: 03/02/2020.},
}
@article {pmid40896239,
year = {2025},
author = {Lorenz, K and Haritoglou, C and Barthelmes, D and Sefat, AMM and Berk, H and Beeke, E and Scheffler, M and Iwersen, M and Müller, B and Ziemssen, F and , },
title = {Treatment Regimens with Ranibizumab in Neovascular Age-Related Macular Degeneration: Real-World Results from the PACIFIC Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {2927-2937},
pmid = {40896239},
issn = {1177-5467},
abstract = {INTRODUCTION: Intravitreal anti-VEGF is the gold standard for treating neovascular age-related macular degeneration (nAMD). The treatment success depends not only on drug efficacy but also on regimen feasibility for physicians and patients. The implementation of different regimen might lead to varying outcomes. "Treat-and-extend" aims to minimize undertreatment with injections at each visit and tailored intervals. This study investigates the utilization and effectiveness of ranibizumab in nAMD, focusing on different treatment regimens in real-world settings.<br><br>MATERIALS AND METHODS: The PACIFIC study, a non-interventional, prospective, multicenter study, included nAMD patients treated with ranibizumab at 185 sites across Germany, the Netherlands and Switzerland. Over 24 months, functional and morphological outcomes were documented for 3051 patients over 24 months, highlighting the practiced treatment regimens.<br><br>RESULTS: A pattern of an observational approach with nevertheless increasing interval extension prevailed (70.4%, 1028 pre-treated; 68.6%, 1090 treatment-na&#xef;ve patients), emerging as the preferred strategy within the first 3 months. Across all regimens, the average number of injections was comparable (mean &#xb1; SD: 7.34&#xa0;&#xb1;&#xa0;5.30 in pre-treated; 7.26&#xa0;&#xb1;&#xa0;4.70 in treatment-na&#xef;ve patients). The treat and extend regimen, however, demonstrated superior effectiveness in improving visual acuity, particularly among treatment-na&#xef;ve patients (number of injections: 7.89&#xa0;&#xb1;&#xa0;5.54 pre-treated; 9.54&#xa0;&#xb1;&#xa0;5.42 treatment-na&#xef;ve patients).<br><br>CONCLUSION: Over 2-year observational period, the treat and extend regimen emerged as a highly effective approach, particularly for those newly diagnosed, with a low risk of undertreatment. Despite its benefits, an unconscious shift to a observe-and-extend or "monitor-and-extend" approach occurred early in treatment, highlighting the need for tailored approaches to optimize patient outcomes in clinical practice.},
}
@article {pmid40895634,
year = {2025},
author = {Liang, X and Wang, J and Zhang, Y and Zheng, H},
title = {Association of serum 25-hydroxyvitamin D levels with age-related macular degeneration and its clinical correlates: a cross-sectional study.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1635739},
pmid = {40895634},
issn = {1664-2392},
mesh = {Humans ; Cross-Sectional Studies ; Female ; *Macular Degeneration/blood/epidemiology/diagnosis ; Male ; *Vitamin D/blood/analogs &amp; derivatives ; Aged ; Middle Aged ; *Biomarkers/blood ; China/epidemiology ; Aged, 80 and over ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults, with significant inter-individual variability in clinical progression. Vitamin D, known for its role in calcium homeostasis and anti-inflammatory pathways, may be implicated in AMD pathogenesis. This study aimed to investigate serum 25-hydroxyvitamin D [25(OH)D] levels in AMD patients and their association with clinical phenotypes.<br><br>METHODS: This single-center, cross-sectional observational study was conducted at Tianjin Eye Hospital, China, involving 210 participants (100 AMD patients and 110 healthy controls). Exclusion criteria included conditions affecting vitamin D metabolism and recent vitamin D supplementation. Comprehensive ophthalmic assessments and laboratory tests were performed. Data were analyzed using R software, employing Student's t-tests, ANONA, chi-squared tests, Pearson correlation and linear regression models.<br><br>RESULTS: AMD patients exhibited significantly lower serum 25(OH)D levels than controls (22.98 &#xb1; 7.30 ng/mL vs. 26.12 &#xb1; 9.81 ng/mL, p=0.013). Within the AMD group, late-stage patients had lower 25(OH)D levels than early-stage patients (22.53 &#xb1; 8.14 ng/mL vs. 23.46 &#xb1; 6.36 ng/mL, p=0.019) and higher CRP levels (0.31 &#xb1; 0.19 mg/L vs. 0.17 &#xb1; 0.05 mg/L, p=0.015). ROC curve analysis indicated moderate diagnostic utility of 25(OH)D for distinguishing AMD patients from controls (AUC=0.714, 95% CI: 0.58-0.73, p<0.01), but limited ability to differentiate early vs. late-stage AMD Linear regression analysis revealed positive associations between 25(OH)D levels and apolipoprotein E (ApoE, &#x3b2;=0.157, p=0.04) and serum creatinine (&#x3b2;=0.18, p=0.02).<br><br>CONCLUSION: This study provides evidence linking lower serum 25(OH)D levels to the presence and severity of AMD, particularly in late-stage disease.},
}
@article {pmid40894055,
year = {2025},
author = {Arnal, L and Mesfin, Y and Xu, C and Salvi, A and Mishra, K and Ludwig, CA},
title = {Beyond Refractive Error: Myopia's Exponential Burden on Retinal Health with Each Diopter.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40894055},
issn = {2693-5015},
support = {K23 EY035741/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND: As myopia reaches epidemic levels worldwide, its role in driving vision-threatening retinal complications is increasingly urgent. This study quantifies the burden of myopia by examining its association with key retinal diseases and how risk escalates with increasing severity.<br><br>METHODS: We conducted a retrospective cohort study using the STARR clinical data warehouse, including all patients with &#x2265;1 documented eye visit. Myopia severity was defined by spherical equivalent and axial length, classifying patients as non-myopic, myopic, highly myopic, or severely myopic. Primary outcomes included six retinal diseases associated with myopia: choroidal neovascularization (CNV), myopic macular degeneration (MMD), foveoschisis, macular hole (MH), rhegmatogenous retinal detachment (RRD), and foveal retinal detachment (FRD). Adjusted logistic regression estimated odds by myopia severity and spherical equivalent. Mean age at diagnosis was compared across groups.<br><br>RESULTS: Retinal complications occurred at younger ages with increasing myopia severity. Compared to non-myopes, myopic, highly myopic, and severely myopic patients had 2.45 (95% CI: 2.36-2.55), 2.46 (95% CI: 2.31-2.62), and 8.15 (95% CI: 7.17-9.27) times higher odds, respectively, of developing any retinal complication. Per diopter increase in myopia, the odds of each complication increased: CNV (OR 1.11; 95% CI: 1.09-1.12), MMD (OR 1.22; 95% CI: 1.18-1.25), foveoschisis (OR 1.22; 95% CI: 1.16-1.28), MH (OR 1.06; 95% CI: 1.05-1.08), FRD (OR 1.23; 95% CI: 1.16-1.32), and RRD (OR 1.10; 95% CI: 1.10-1.11). In severe myopes, odds were markedly elevated: CNV (OR 22.90), MMD (OR 60.19), foveoschisis (OR 102.98), MH (OR 6.69), FRD (OR 22.72), and RRD (OR 6.84).<br><br>CONCLUSIONS: Myopia is independently associated with higher odds of retinal diseases, and this risk increases incrementally with severity. These findings support a dose-response relationship and highlight the importance of early risk stratification, tailored monitoring, and timely referral in patients with high and severe myopia.},
}
@article {pmid40893624,
year = {2025},
author = {Erb, BM and Botros, E and Saunders, TF and Haas, AM and Voland, R and Linderman, R and Domalpally, A and Csaky, KG},
title = {Investigating Macular Tissue Integrity Index as a Novel Biomarker in Geographic Atrophy.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100871},
pmid = {40893624},
issn = {2666-9145},
abstract = {PURPOSE: The rate of geographic atrophy (GA) enlargement is commonly used as an outcome in clinical trials. However, this metric typically lacks specificity for central macular involvement and structure-function relationships. We propose a targeted approach in monitoring GA progression within the central macula, highlighting the limited benefit of including GA expansion beyond the 3-mm perifoveal zone when analyzing visual function. This study evaluates how retinal tissue and photoreceptor integrity within the central 1-mm and 3-mm circles centered on the fovea correlate with visual function.<br><br>DESIGN: Retrospective, longitudinal analysis of a GA clinical trial cohort.<br><br>SUBJECTS: Forty-three eyes from 43 participants enrolled in GA clinical trials.<br><br>METHODS: Baseline and 1-year fundus autofluorescence (FAF) and OCT scans were analyzed. The percentages of non-GA areas within the 1-mm and 3-mm circles centered on the fovea were quantified to calculate the Macular Tissue Integrity Index (MTII) using FAF images. The percentages of intact ellipsoid zones within the same circles were used to define the EZ Integrity Index (EZII). Longitudinal changes in MTII and EZII were compared to overall GA area growth and change in visual acuity (VA).<br><br>MAIN OUTCOME MEASURES: Correlations between MTII, EZII, GA area, and VA (best-corrected VA [BCVA] and low-luminance VA [LLVA]) were assessed.<br><br>RESULTS: Macular Tissue Integrity Index and EZII within the central 1 mm correlated significantly with BCVA (R[2] = 0.20, P = 0.003 and R[2] = 0.29, P < 0.001, respectively), while EZII in the 3-mm zone correlated with both BCVA and LLVA (R[2] = 0.17, P < 0.01 for both). Changes in MTII or EZII over time were not associated with GA area growth or with baseline integrity indices.<br><br>CONCLUSIONS: Macular Tissue Integrity Index and EZII are novel biomarkers for macular photoreceptor integrity, with distinct correlations to BCVA and LLVA depending on the measurement zone. These findings support the utility of MTII and EZII in assessing macular integrity and highlight the heterogeneity of GA progression, warranting further validation in larger studies.},
}
@article {pmid40893621,
year = {2025},
author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Wang, YX and Nangia, V and Panda-Jonas, S},
title = {Macular Atrophic versus Subretinal Proliferative Changes in Myopic and Age-Related Macular Degeneration: The 2-Continent Eye Study.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100885},
pmid = {40893621},
issn = {2666-9145},
abstract = {OBJECTIVE: To assess the prevalences of subfoveal retinal pigment epithelium (RPE) loss versus subfoveal tissue proliferation as causes of vision loss in patients with late-stage age-related macular degeneration (AMD) or myopic macular atrophy.<br><br>DESIGN: Population-based studies conducted in Russia, China, and India and histological examination of enucleated human globes.<br><br>PARTICIPANTS: The Russian Ural Eye and Medical Study (n = 5899 participants; age: &#x2265;40 years), Ural Very Old Study (n = 1526; age: 85+ years), Beijing Eye Study (n = 3468; age: &#x2265;40 years), and Central India Eye and Medical Study (n = 4711) were conducted in rural and urban regions in Bashkortostan/Russia, Beijing/China, and Nagpur/India, respectively. The histological study part included human eyes enucleated because of reasons like malignant melanomas, or were post mortem enucleated.<br><br>METHODS: The participants underwent a series of general medical and ophthalmological examinations including OCT of the macula. In the histological study part, the enucleated globes were histomorphometrically examined.<br><br>MAIN OUTCOME MEASURES: Presence of RPE loss and of subretinal proliferations.<br><br>RESULTS: In all 4 population-based studies combined, late-stage AMD and myopic macular atrophy were detected in 291 eyes and 46 eyes, respectively. Retinal pigment epithelium cell loss was dominant in 136 (94%) out of 145 eyes with geographic atrophy and in 35 (76%) out of 46 eyes with myopic macular atrophy, whereas subretinal proliferations were predominantly present in 127 (87%) out of 146 eyes with neovascular AMD. Among all 337 eyes with late AMD or myopic macular atrophy, RPE loss was the main cause for vision loss in 190 (56%) eyes and subretinal proliferations in 147 (44%) eyes, with no significant difference (P > 0.05) between the study cohorts. In the histological specimen, subretinal proliferations included melanin-bearing cells in contact with a periodic acid-Schiff-positive membrane, resembling RPE cells.<br><br>CONCLUSIONS: Subretinal proliferations in the foveal region were the main reason for central visual acuity loss in 44% of all eyes with late AMD or myopic macular atrophy in 4 population-based studies. Subretinal foveal RPE cell proliferation and RPE loss are roughly equally important as a cause of vision loss in AMD and myopic macular atrophy.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40893620,
year = {2025},
author = {Wu, Z and Blodi, BA and Holz, FG and Jaffe, GJ and Liakopoulos, S and Sadda, SR and Schmitz-Valckenberg, S and Bonse, M and Brown, T and Choong, J and Clifton, B and Corradetti, G and Hodgson, LAB and Lentzsch, AM and Mahmoudi, A and Pak, JW and Saßmannshausen, M and Skalak, C and von der Emde, L and Winkler, J and Guymer, RH},
title = {OCT-Defined Atrophic Age-Related Macular Degeneration Changes Associated with Deep Visual Sensitivity Losses: A Multicenter Study.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100884},
pmid = {40893620},
issn = {2666-9145},
abstract = {PURPOSE: To identify combination(s) of OCT changes that define atrophic age-related macular degeneration (AMD) lesions associated with repeatable deep visual sensitivity defects.<br><br>DESIGN: Reader study.<br><br>PARTICIPANTS: One hundred seventy-one OCT scans from 60 eyes of 53 participants.<br><br>METHODS: Participants underwent 2 high-density targeted microperimetry tests (Macular Integrity Assessment device with Goldmann Size III stimuli) per visit of a 3.5&#xb0; (approximately 1000 &#x3bc;m) diameter region-of-interest that had evidence of at least incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA). OCT B-scans within the region sampled on microperimetry were annotated by 12 readers from 6 established reading centers for 7 different features related to RPE and outer retinal atrophy. The prevalence of the presence of a repeatable &#x2264;10 decibel (dB) defect on microperimetry for lesions categorized by 18 different combinations of such features, or criteria, was determined.<br><br>MAIN OUTCOME MEASURES: The criteria for OCT-defined atrophic changes showing a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect, which has previously shown to be characteristic of regions with a truly nonresponding test location on microperimetry.<br><br>RESULTS: Sixty percent of complete RPE and outer retinal atrophy (cRORA) lesions-based on the presence of hypertransmission and RPE abnormalities &#x2265;250 &#x3bc;m in width, with evidence of overlying photoreceptor (PR) degeneration, on an OCT B-scan-had a repeatable &#x2264;10 dB defect. However, between 92% and 98% of lesions with both hypertransmission and complete RPE loss &#x2265;500 &#x3bc;m, and with evidence of any size of any feature of overlying PR degeneration, had a repeatable &#x2264;10 dB defect, depending on the criteria considered. Between 92% and 95% of lesions with hypertransmission &#x2265;500 &#x3bc;m and either overlying external limiting membrane disruption, or outer plexiform layer and inner nuclear layer subsidence, and/or hyporeflective wedge-shaped band(s) &#x2265;500 &#x3bc;m, with or without RPE abnormalities, had a repeatable &#x2264;10 dB defect.<br><br>CONCLUSIONS: This study identified various criteria for OCT-defined atrophic AMD lesions with functional characteristics that can be expected of regions with a truly nonresponding test location on high-density targeted microperimetry testing (i.e., having a &#x2265;90% prevalence of a repeatable &#x2264;10 dB defect). Such OCT-defined lesions could thus serve as functionally relevant clinical endpoints of end-stage atrophic AMD to facilitate preventative treatment trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40893340,
year = {2025},
author = {Sattah, N and Zhao, W and Choi, A and Chi, M and Sarici, K and Weng, P and Morgan, R and Zheng, Y and Karthik, N and Vajzovic, L and Hadziahmetovic, M},
title = {Effect of Faricimab on Visual Acuity and Retinal Structure in Neovascular Age-Related Macular Degeneration Previously Treated With Anti-VEGF Therapy.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251366393},
pmid = {40893340},
issn = {2474-1272},
abstract = {Purpose: To evaluate the effects of switching from traditional antivascular endothelial growth factor (anti-VEGF) therapies to faricimab, a biclonal antibody that targets both VEGF and angiopoietin-2, on eyes with neovascular age-related macular degeneration (nAMD). Methods: This study retrospectively reviewed patients with nAMD who were previously treated with bevacizumab, ranibizumab, or aflibercept and then switched to faricimab. We compared injection frequency and visual acuity (VA) during the time period before faricimab initiation (1 year prior) and after initiation (6-12 months after). Optical coherence tomography images were analyzed from initiation to final follow-up (6-12 months after initiation). Results: We evaluated 84 eyes of 68 patients. Following faricimab initiation, eyes had a reduced mean ± SE central macular thickness (CMT) (282.3 ± 16.2 μm vs 244.8 ± 14.3 μm; P < .01). Annual injection frequency increased from 7.73 ± 0.33 to 8.66 ± 0.28 injections (P < .001). VA did not change significantly during the year before faricimab initiation (P = .539) but decreased after initiation (from 0.56 ± 0.05 logMAR to 0.66 ± 0.06 logMAR; P < .01). Four eyes developed macular atrophy following faricimab initiation (P < .01). Conclusions: Eyes with nAMD that were previously treated with anti-VEGF therapy and later switched to faricimab showed reduced CMT; however, some patients had increased injection frequency, decreased VA, and macular atrophy. These findings should be explored further using larger datasets.},
}
@article {pmid40893119,
year = {2025},
author = {Barthelemy, N and Tailor, P and Sridhar, J and Samarakoon, T and Sengillo, JD},
title = {Effects of Socioeconomic Factors on Visual Outcome and Management of Wet Age-Related Macular Degeneration Patients.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004649},
pmid = {40893119},
issn = {1539-2864},
abstract = {PURPOSE: To analyze the relationship between socioeconomic status (SES) and neovascular age-related macular degeneration (nAMD) outcomes and management.<br><br>METHODS: Retrospective analysis of 1449 patients diagnosed with nAMD, treated with anti-VEGF between January 2016-January 2024.<br><br>RESULTS: Lower income was associated with poorer baseline (p < .001) and final (p < .001) BCVA. Worse final visual acuity correlated with lower baseline BCVA (p < .001), lower income (p = .05) and older age (p < .001); insurance type did not (p = .558). Non-Hispanic/non-Latino patients exhibited a higher rate of delayed injections per scheduled visit than Hispanics (p =.002). Ethnicity correlated with insurance status (p = .008); Hispanic or Latino patients more often had Medicaid or commercial insurance; non-Hispanics/non-Latino patients more often had Medicare. Higher-income patients were more likely to receive aflibercept (p < .001) and faricimab (p =.021). Hispanic or Latino were more likely to receive bevacizumab (OR 2.49; p < .001), but insurance type modified this association (OR 3.42; p = .010).<br><br>CONCLUSIONS: Lower income correlated with worse nAMD visual outcomes, and the type of anti-VEGF treatment used varied across income and ethnicity groups, but not insurance type.},
}
@article {pmid40893118,
year = {2025},
author = {Wakugawa, S and Imanaga, N and Terao, N and Kuroshima, C and Miyara, Y and Maehira, M and Koizumi, H},
title = {Changes in widefield choroidal thickness after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004651},
pmid = {40893118},
issn = {1539-2864},
abstract = {PURPOSE: This study aimed to investigate changes in choroidal thickness using widefield optical coherence tomography following anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD).<br><br>METHODS: We examined 69 patients with unilateral neovascular AMD. All patients underwent three monthly intravitreal injections of anti-VEGF agents. Widefield choroidal thickness within an 18-mm circular glid centered on the fovea, subdivided into nine areas, was evaluated at baseline and at 3 months.<br><br>RESULTS: Forty-two and 27 patients were classified into the AMD and pachychoroid neovasculopathy (PNV) groups, respectively. At 3 months, the treated eyes in both groups showed significantly and extensively reduced choroidal thickness (P < 0.01 for all areas). The untreated fellow eyes in the PNV group also showed decreased choroidal thickness at 3 months (P < 0.05 for all areas). Complete retinal fluid resolution was significantly associated with a greater decrease ratio of choroidal thickness in the PNV group (P < 0.05 for all areas).<br><br>CONCLUSION: Anti-VEGF therapy for neovascular AMD led to extensively decreased choroidal thickness. In patients with PNV, a greater decrease in overall choroidal thickness appeared to be associated with more effective resolution of retinal fluid. Observation of widefield choroidal thickness may be important for the management of neovascular AMD.},
}
@article {pmid40890721,
year = {2025},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Can artificial intelligence with multimodal imaging outperform traditional methods in predicting age-related macular degeneration progression? A systematic review and exploratory meta-analysis.},
journal = {BMC medical informatics and decision making},
volume = {25},
number = {1},
pages = {321},
pmid = {40890721},
issn = {1472-6947},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/diagnosis ; *Artificial Intelligence/standards ; Disease Progression ; *Multimodal Imaging/methods/standards ; Sensitivity and Specificity ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, and its prevalence is expected to rise with aging populations. Early prediction of AMD progression is critical for effective management. This systematic review and meta-analysis evaluate the accuracy, sensitivity, and specificity of artificial intelligence (AI) algorithms in in detecting and predicting progression of AMD.<br><br>METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review and meta-analysis were conducted from inception to February 7th, 2025. We included five studies that assessed the performance of AI algorithms in predicting AMD progression using multimodal imaging. Data on accuracy, sensitivity, and specificity were extracted, and meta-analysis was performed using Comprehensive Meta-Analysis software version 3.7. Heterogeneity was assessed using the I&#xb2; statistic.<br><br>RESULTS: Of the five studies, AI models demonstrated superior accuracy (mean difference: 0.07, 95% CI: 0.07, 0.07; p&#x2009;<&#x2009;0.00001) and sensitivity (mean difference: 0.08, 95% CI: 0.08, 0.08; p&#x2009;<&#x2009;0.00001) compared to retinal specialists. Specificity also showed a minimal but significant advantage for AI (mean difference: 0.01, 95% CI: 0.01, 0.01; p&#x2009;<&#x2009;0.00001). Importantly, heterogeneity was minimal to absent across all analyses (I&#xb2; = 0-0.42%), supporting the reliability and consistency of pooled findings.<br><br>CONCLUSION: AI algorithms outperform retinal specialists in predicting AMD progression, particularly in accuracy and sensitivity. These findings support the potential of AI in AMD prediction; however, given the limited number of included studies, the results should be interpreted as exploratory and in need of validation through future large-scale, prospective studies.},
}
@article {pmid40890572,
year = {2025},
author = {Lynch, AM and Drolet, DW and Trinder, KM and Gupta, S and Westacott, MJ and Janjic, N and Palestine, AG and Patnaik, JL and Mathias, MT and Mandava, N and Wagner, BD},
title = {Proteomic profiles in the aqueous following anti-vegf therapy in treatment naïve neovascular age-related macular degeneration.},
journal = {Clinical proteomics},
volume = {22},
number = {1},
pages = {32},
pmid = {40890572},
issn = {1542-6416},
abstract = {BACKGROUND/STUDY OBJECTIVES: Age-related macular degeneration (AMD), a degenerative disease of the photoreceptor support system of the macula, is a leading cause of vision loss in individuals over 60 years of age. In this exploratory longitudinal study, we studied VEGF-related proteins and other protein concentrations in the aqueous humor of patients with treatment naïve neovascular AMD (defined as patients with a previously untreated and recently diagnosed advanced neovascular form of AMD (NVAMD) who were eligible for an intra-vitreal administration of an anti-VEGF agent to treat choroidal neovascularization). The objectives of this small pilot study were: (1) To determine levels of VEGF-related proteins in the aqueous humor of treatment naïve NVAMD patients compared with control patients, (2) To determine whether levels of VEGF-related proteins change over time with anti-VEGF injections in NVAMD patients, (3) To put these differences into perspective relative to all protein targets and identify other off-target (non-VEGF) proteins that may be related to NVAMD or NVAMD treatment.<br><br>METHODS: We used an aptamer-based proteomic technology to study protein concentrations. Cases had a sample of aqueous collected immediately prior to starting the anti-VEGF intra-vitreal injection and at two follow-up visits. Controls were cataract patients with no AMD. Aqueous was collected at the time of cataract surgery.<br><br>RESULTS: Comparison between 9 cases and 11 controls revealed 56 proteins, out of 3,803 targets, with significant differences in baseline levels. After treatment, a decline in aqueous VEGF concentrations was indicated from two aptamer reagents, while a third recorded a significant increase. Interference studies demonstrated that the increase in levels observed for the latter reagent was due to measuring both drug-bound and free VEGF concentrations (total VEGF) while the others measured only free VEGF.<br><br>CONCLUSIONS: In this exploratory study, 56 proteins were identified that could potentially be linked with NVAMD. In interference studies free aqueous VEGF levels declined while total VEGF levels increased following anti-VEGF treatment. No large off-target effects on the proteome were observed with treatment. We illustrate how the protein interactome can mask or potentially unmask binding epitopes leading to signal changes not necessarily related to the absolute protein level.},
}
@article {pmid40889625,
year = {2025},
author = {Agathos, CP and Shanidze, NM and Fletcher, DC},
title = {Importance of Screening for Contrast Sensitivity, Falls, and Mobility Limitations in Older Adults With Maculopathy.},
journal = {American journal of ophthalmology},
volume = {280},
number = {},
pages = {481-492},
pmid = {40889625},
issn = {1879-1891},
support = {90REGE0018/ACL/ACL HHS/United States ; R01 EY036172/EY/NEI NIH HHS/United States ; T32 EY025201/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Contrast Sensitivity/physiology ; Cross-Sectional Studies ; Female ; Male ; Aged ; *Accidental Falls/statistics &amp; numerical data ; Visual Acuity/physiology ; Middle Aged ; *Mobility Limitation ; *Macular Degeneration/physiopathology/diagnosis/complications ; Surveys and Questionnaires ; *Vision, Low/physiopathology/rehabilitation/diagnosis ; Aged, 80 and over ; Vision, Binocular/physiology ; *Vision Screening/methods ; Postural Balance/physiology ; },
abstract = {OBJECTIVE: Assess the potential value of adding questions on falls/balance difficulties due to vision loss and testing contrast sensitivity (CS) in patients with maculopathy (mainly age-related macular degeneration, AMD) to help guide referral for mobility rehabilitation.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: A total of 125 patients over 55 years old with binocular maculopathy and intact peripheral vision presenting for a low vision rehabilitation consultation.<br><br>METHODS: Patients were asked questions regarding difficulties with their balance and mobility, including the 9-item Glaucoma Activity Limitation questionnaire (GAL-9). For analysis, patients were grouped by visual impairment severity using better-eye visual acuity (VA) and binocular CS.<br><br>MAIN OUTCOME MEASURES: Visual function, self-reported balance and mobility difficulties, falls history, and rehabilitation referrals were examined across visual impairment severity groups.<br><br>RESULTS: Total 52% of patients reported balance or gait difficulties and 36% attributed mobility limitations to vision loss. Increasing vision deficit severity related to greater mobility concerns (>50% of patients in the severe categories rated difficulty as 3/5 or higher) and higher referral rates. Scores on the GAL-9 increased with greater vision loss and were predicted by CS, female sex, larger relative scotomata and falls history (R[2] = 0.45, P < .0001). CS was a better predictor of mobility difficulties than VA. Based on reported concerns, 31.2% of patients were referred to orientation and mobility training and/or physical therapy (>50% in the severe groups).<br><br>CONCLUSIONS: Mobility limitations and falls affect a substantial proportion of AMD patients yet may go undiscussed in eye clinics. Incorporating screening questions and explicit discussion of mobility difficulties in clinical practice in maculopathy can help elucidate patient mobility limitations. Realization of these limitations is the prerequisite to initiate appropriate referrals to low vision and mobility specialists to improve mobility and manage falls risk. Clinical practice may also benefit from assessment of CS as this is a better indicator of difficulties in daily living. Our results, along with prior literature, underscore the need to recognize the role of central vision loss, and vision loss more broadly, in mobility decline. Thus, a central vision loss-specific mobility questionnaire may be needed to facilitate patient screening in the future.},
}
@article {pmid40889611,
year = {2025},
author = {Alzu'bi, A and Momany, S and Aleshawi, A and Tashtoush, M and Al-Dwairi, R},
title = {The utility of artificial intelligence in characterization and detecting causes of macular edema: A spectral-domain OCT-based algorithm study.},
journal = {Experimental eye research},
volume = {260},
number = {},
pages = {110619},
doi = {10.1016/j.exer.2025.110619},
pmid = {40889611},
issn = {1096-0007},
mesh = {*Macular Edema/diagnosis/etiology/diagnostic imaging ; Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Algorithms ; *Diabetic Retinopathy/complications/diagnosis ; *Artificial Intelligence ; Deep Learning ; Macular Degeneration/complications/diagnosis ; Neural Networks, Computer ; },
abstract = {BACKGROUND: Macular Edema (ME), a prevalent cause of vision loss, can arise from various retinal conditions, most notably diabetic macular edema (DME) and age-related macular degeneration (AMD). Accurate and timely differentiation among these causes is necessary for appropriate treatment; however, it remains a diagnostic challenge. This research addresses the gap in automated ME classification by developing and evaluating a deep learning framework capable of distinguishing between DME, AMD, and normal retinal conditions using optical coherence tomography (OCT) images.<br><br>METHODS: A retrospective dataset comprising 1040 OCT images from King Abdullah University Hospital (KAUH) was used in conjunction with a public dataset for benchmarking. The dataset was divided into annotated and non-annotated images, with preprocessing, augmentation, and simulated segmentation applied to improve the model performance. We benchmarked and evaluated three pretrained convolutional neural networks-ResNet152, InceptionV3, and MobileNetV2.<br><br>RESULTS: Among the models, InceptionV3 and ResNet152 achieved the highest accuracies (95&#xa0;%-98&#xa0;%) across both datasets. MobileNetV2, on the other hand, showed moderate accuracy on the KAUH dataset (89&#xa0;%) but exhibited strong performance on the public dataset (97&#xa0;%). Explainable AI (XAI) techniques, specifically Grad-CAM, were applied to visualize the model predictions, and the outcomes were manually validated against annotated data to assess interpretability.<br><br>CONCLUSIONS: The findings support the integration of a robust CNN architecture and XAI techniques to enhance diagnostic precision and aid clinical decision-making in ophthalmology.},
}
@article {pmid40889610,
year = {2025},
author = {Navratil, EM and Wenzel, PA and Flamme-Wiese, MJ and Miller, JEB and Wiley, LA and Stone, EM and Tucker, BA and Mullins, RF},
title = {Sialoglycoconjugate profiling of human choroid, retinal pigment epithelium, and basal laminar deposits.},
journal = {Experimental eye research},
volume = {260},
number = {},
pages = {110618},
pmid = {40889610},
issn = {1096-0007},
support = {P30 EY025580/EY/NEI NIH HHS/United States ; R01 EY024605/EY/NEI NIH HHS/United States ; R01 EY033308/EY/NEI NIH HHS/United States ; T32 GM145441/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; *Choroid/metabolism ; Aged ; Aged, 80 and over ; *Macular Degeneration/metabolism ; Female ; Male ; Plant Lectins/metabolism ; *Glycoconjugates/metabolism ; Middle Aged ; Ribosome Inactivating Proteins ; },
abstract = {Age-related macular degeneration is a leading cause of central vision loss in the elderly. Early hallmarks of the disease include basal laminar deposit beneath the retinal pigment epithelium (RPE) and choriocapillaris degeneration. We utilized sialic acid binding lectins Sambucus nigra/Elderberry Bark Lectin (EBL) and Maackia amurensis lectin II (MAL-II), to assess the localization of ɑ-2,6 and ɑ-2,3 sialic acids, respectively, in human macular retina, RPE, basal laminar deposits, and choroid. Photoreceptor carbohydrate epitopes differ based on retinal topography, with MAL-II recognizing foveal (but not extrafoveal) cones. Both MAL-II and EBL react with apical RPE, and both bind basal laminar deposits. In the choroid, MAL-II predominantly labels the choriocapillaris endothelium, while EBL also shows robust labeling of Bruch's membrane and extracellular domains surrounding the microvasculature (intercapillary pillars). EBL labeling overlaps with the distribution of complement factor H to a greater extent than MAL-II. After treatment with neuraminidase to remove terminal sialic acids, a battery of lectins was applied to sections of choroids. Lectins that recognize β-galactose, N-acetyllactosamine, galactose (β-1,3) N-acetylgalactosamine, and ɑ- or β-N-acetylgalactosamine showed increased reactivity, indicating the presence of abundant sialoglycans in basal laminar deposits. This study provides insight into the location and partial identities of sialoglycoconjugates in the human choroid, with possible implications for understanding the pathogenesis of macular degeneration.},
}
@article {pmid40874706,
year = {2025},
author = {Chen, W and Li, Z and Zhou, X and Li, C and Lin, Y},
title = {Identification of Biomarkers for Oxidative Stress in Age-Related Macular Degeneration: Combining Transcriptomics and Mendelian Randomization Analysis.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {8},
pages = {42},
pmid = {40874706},
issn = {2164-2591},
mesh = {*Oxidative Stress/genetics/physiology ; Biomarkers/analysis/metabolism ; *Macular Degeneration/diagnosis/genetics/physiopathology/prevention &amp; control ; Mendelian Randomization Analysis ; Machine Learning ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Datasets as Topic ; Humans ; },
abstract = {PURPOSE: Oxidative stress has long been recognized as a significant influence in the pathophysiology of age-related macular degeneration (AMD). Therefore there is a need to explore the relationship between oxidative stress-related biomarkers and AMD.<br><br>METHODS: Based on Gene Expression Omnibus database-Gene Expression Omnibus Series (GSE)29801 and GSE135092 datasets, three machine learning methods were used to screen biomarkers. The Wilcoxon test was used to compare the percentage of immune cells in control and AMD samples. The causal relationship between biomarkers and AMD was explored in a series of Mendelian randomization (MR) analyses. Ultimately, the expression levels of biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the simulated AMD cell model.<br><br>RESULTS: A total of 16 differentially expressed oxidative stress-related genes (DE-OSRGs) were screened. Functional enrichment analysis indicated that DE-OSRGs participated in cellular senescence, cell cycle regulation, and PPAR signaling pathways. Machine learning methods were used to screen for five biomarkers (GFAP, Stearoyl-CoA desaturase [SCD], BCKDHB, GPX8, and MSRB2). The qRT-PCR results showed that the expression levels of five biomarkers were significantly different between the simulated AMD cell model and control groups. Spearman correlation analysis showed that GPX8 had the highest positive correlation with M2 macrophages (correlation coefficient [cor] = 0.36, P < 0.01), and SCD had a strong negative correlation with eosinophils (cor = -0.28, P < 0.05). MR results revealed that BCKDHB played a crucial role as a risk factor for AMD (odds ratio > 1, P < 0.05).<br><br>CONCLUSIONS: This study screened the biomarkers related to oxidative stress in AMD, providing a certain theoretical basis for the prevention and clinical diagnosis of AMD.<br><br>TRANSLATIONAL RELEVANCE: Identifying biomarkers with diagnostic value for AMD could provide new understanding of its pathogenesis, and open up potential targets for clinical intervention.},
}
@article {pmid40874698,
year = {2025},
author = {Olivieri, C and Fai, A and Bhutto, IA and McLeod, DS and Neri, G and Reibaldi, M and Edwards, MM and Borrelli, E},
title = {Retinal Vessel Changes in Geographic Atrophy in AMD: Insights From Imaging and Histology.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {69},
pmid = {40874698},
issn = {1552-5783},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy/diagnosis/pathology/etiology/physiopathology ; Tomography, Optical Coherence/methods ; Female ; Male ; *Retinal Vessels/pathology/diagnostic imaging ; Aged ; Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Middle Aged ; *Macular Degeneration/complications ; Fundus Oculi ; },
abstract = {PURPOSE: The purpose of this study was to investigate retinal vascular changes in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA), and to correlate imaging findings with histology.<br><br>METHODS: Sixty subjects were enrolled: 20 with GA, 20 with intermediate AMD, and 20 healthy controls. SS-OCTA imaging was used to quantify retinal perfusion density (PD) and vessel length density (VLD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and full retina. A topographical analysis distinguished regions with and without retinal pigment epithelium (RPE) atrophy in GA eyes. Additionally, flat-mount immunohistochemistry was performed on a donor eye with GA to assess retinal vasculature. Main outcome measures included PD and VLD across SCP, DCP, and full retina, in regions with and without RPE atrophy.<br><br>RESULTS: Retinal PD and VLD were significantly reduced in GA eyes compared with intermediate AMD eyes, particularly in the DCP. Topographical analysis revealed more pronounced vascular impairment in areas with RPE atrophy, whereas regions without RPE atrophy in GA eyes exhibited perfusion comparable to intermediate AMD and healthy controls. Histological analysis confirmed a substantial reduction in vascular density within atrophic regions.<br><br>CONCLUSIONS: Retinal vascular changes in GA predominantly occur within regions of RPE atrophy. The preservation of perfusion in regions without RPE atrophy suggests that vascular impairment is localized. These findings underscore the importance of regional analysis and histopathologic correlation in understanding vascular remodeling in GA. Future longitudinal OCTA studies are warranted to clarify the temporal progression of these vascular alterations in relation to RPE atrophy.},
}
@article {pmid40888531,
year = {2025},
author = {Charmasson, M and Mairot, K and Gascon, P and Dalmas, F and David, T and Comet, A},
title = {Short-term efficacy of faricimab switch on retinal exudative signs in patients requiring frequent anti-VEGF injections : A real-life study.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251374263},
doi = {10.1177/11206721251374263},
pmid = {40888531},
issn = {1724-6016},
abstract = {ObjectiveTo evaluate the efficacy of switching from anti-vascular endothelial growth factor (VEGF) to faricimab in reducing exudative signs in age-related macular degeneration (AMD) patients receiving regular injections (every 8 weeks or less) without restarting a standard induction regimen.MethodsThis retrospective, observational, multicenter study included patients with exudative AMD previously treated with aflibercept 2 mg or ranibizumab every ≤8 weeks and switched to faricimab while maintaining their previous injection interval. The first follow-up visit occured after switching to faricimab, with a single injection, and corresponded to the pre-existing injection interval. Primary outcomes included changes in subretinal (SRF) and intraretinal fluid (IRF).ResultsAmong 39 patients (47 eyes), the proportion of eyes with SRF decreased from 43.1% to 23.5% (p < 0.01) and IRF from 43.8% to 19.6% (p < 0.01). SRF height significantly reduced from 75.3 μm to 60 μm (p = 0.04). Pigment epithelial detachment (PED) height decreased from 223 μm to 164μm (p < 0.01), and central retinal thickness (CRT) declined from 273.7 μm to 268 μm (p < 0.01). Injection intervals extended by an average of 7 days (40 to 47 days, p < 0.01). No significant changes in BCVA (p = 0.14) were observed. No adverse events were reported.ConclusionsSwitching to faricimab without restarting an induction phase effectively reduces SRF and IRF while modestly extending injection intervals in patients requiring frequent anti-VEGF injections. These findings suggest a potential benefit in treatment burden reduction. Further studies are needed to assess long-term visual outcomes and safety.},
}
@article {pmid40886774,
year = {2025},
author = {Lai, TYY and Kataoka, K and Hsieh, YT and Apte, RS and Bhende, M and Chang, A and Chiakitmongkol, V and Chen, Y and Chen, LJ and Cheung, GCM and Chhablani, J and Fong, KCS and Guymer, RH and Gomi, F and Huang, SS and Kim, JE and Kokame, GT and Koh, A and Li, X and Lim, JI and Ng, DSC and Okada, AA and Radke, NV and Sadda, SR and Sasaki, M and Sivaprasad, S and Shanmugam, MP and Verma, L and Wong, TY and Zhang, X and Lam, DSC},
title = {International consensuses and guidelines on etiology, diagnosis, treatment, and future developments of neovascular age-related macular degeneration (nAMD) by the Asia-Pacific Vitreo-retina Society (APVRS), the Asia-Pacific Ocular Imaging Society (APOIS) and the Academy of the Asia-Pacific Professors of Ophthalmology (AAPPO).},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100242},
doi = {10.1016/j.apjo.2025.100242},
pmid = {40886774},
issn = {2162-0989},
abstract = {Neovascular age-related degeneration (nAMD) is one of the leading causes of visual impairment in older populations in the developed world. With the aging population, the incidence of nAMD is growing globally. Despite advancements in diagnostic investigations and treatment modalities over the past three decades, there remains considerable controversies in the pathogenesis, classification and optimal management strategies. An international panel of 31 experts from 11 countries/regions prepared and voted on consensus statements in five key areas: (1) etiology controversies; (2) diagnosis controversies; (3) treatment controversies; (4) future development controversies; and (5) healthcare deliveries controversies. Among the 31 consensus statements, 28 (90.3 %) have achieved over 75 % agreement. These statements can provide a practical guide for ophthalmologists to provide the optimal care of patients with nAMD and for planning future research priorities in order to address the unmet needs in nAMD.},
}
@article {pmid40881460,
year = {2025},
author = {Dwomoh, EA and Prasad, A and Nanda, T},
title = {Sterile Intraocular Inflammation in Patients Receiving Both Faricimab and High-Dose Aflibercept in Consecutive Order.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251365391},
pmid = {40881460},
issn = {2474-1272},
abstract = {Purpose: To describe 3 cases of intraocular inflammation (IOI) in patients who received faricimab and high-dose aflibercept in consecutive order. Methods: Retrospective case review. Results: Three patients, 2 with neovascular age-related macular degeneration (nAMD) and 1 with central retinal vein occlusion (CRVO), transitioned from 2 mg aflibercept to either faricimab (in cases 1 and 2) or high-dose aflibercept (in case 3) due to persistent disease activity. In all cases, contemporary medication provided minimal effect. Subsequently, patients in cases 1 and 2 were switched to high-dose aflibercept at their next visit, and the patient in case 3 was switched to faricimab. On follow-up, the disease worsened in all 3 cases. Each patient returned to their previous drug. Shortly after, each patient developed an episode of IOI. Conclusions: Patients receiving different high-dose or longer-acting agents in short order may be at risk for developing antidrug antibodies and IOI.},
}
@article {pmid40867529,
year = {2025},
author = {Donaldson, KJ and Chrenek, MA and Boatright, JH and Nickerson, JM},
title = {High-Resolution Imaging and Interpretation of Three-Dimensional RPE Sheet Structure.},
journal = {Biomolecules},
volume = {15},
number = {8},
pages = {},
pmid = {40867529},
issn = {2218-273X},
support = {R01 EY028859/EY/NEI NIH HHS/United States ; P30 EY006360/EY/NEI NIH HHS/United States ; I21 RX001924/RX/RRD VA/United States ; R01 DC009246/DC/NIDCD NIH HHS/United States ; T32 EY007092/EY/NEI NIH HHS/United States ; I01 RX002806/RX/RRD VA/United States ; 5 R01 EY028450 01-05/EY/NEI NIH HHS/United States ; R01 EY021592/EY/NEI NIH HHS/United States ; R01 EY028450/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism/cytology/diagnostic imaging/pathology ; *Imaging, Three-Dimensional/methods ; Humans ; Animals ; Microscopy, Confocal ; Macular Degeneration/pathology/metabolism ; Zonula Occludens-1 Protein/metabolism ; },
abstract = {The retinal pigment epithelium (RPE), a monolayer of pigmented cells, is critical for visual function through its interaction with the neural retina. In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), dysmorphic traits like cell enlargement and apparent multinucleation emerge. Multinucleation has been hypothesized to result from cellular fusion, a compensatory mechanism to maintain cell-to-cell contact and barrier function, as well as conserve resources in unhealthy tissue. However, traditional two-dimensional (2D) imaging using apical border markers alone may misrepresent multinucleation due to the lack of lateral markers. We present high-resolution confocal images enabling three-dimensional (3D) visualization of apical (ZO-1) and lateral (α-catenin) markers alongside nuclei. In two RPE damage models, we find that seemingly multinucleated cells are often single cells with displaced neighboring nuclei and lateral membranes. This emphasizes the need for 3D analyses to avoid misidentifying multinucleation and underlying fusion mechanisms. Lastly, images from the NaIO3 oxidative damage model reveal variability in RPE damage, with elongated, dysmorphic cells showing increased ZsGreen reporter protein expression driven by EMT-linked CAG promoter activity, while more regular RPE cells displayed somewhat reduced green signal more typical of epithelial phenotypes.},
}
@article {pmid40886207,
year = {2025},
author = {Ekinci, O},
title = {Successful treatment of Charles Bonnet syndrome after cerebellar stroke in a patient with binocular macular degeneration with low dose brexpiprazole: a case report.},
journal = {Acta neurologica Belgica},
volume = {125},
number = {6},
pages = {1681-1684},
pmid = {40886207},
issn = {2240-2993},
}
@article {pmid40885885,
year = {2025},
author = {Bao, S and Yang, Z and Zhang, Z and Qu, J and Sun, J},
title = {AttResAMD: An Attention-Driven Deep Learning Framework for Expert-Level Automated Classification of Age-Related Macular Degeneration from Fundus Photography.},
journal = {Interdisciplinary sciences, computational life sciences},
volume = {},
number = {},
pages = {},
pmid = {40885885},
issn = {1867-1462},
}
@article {pmid40885419,
year = {2025},
author = {Mahmoudzadeh, R and Zaichik, M and Farhani, K and Salabati, M and Randolph, J},
title = {Antidepressant Use and Incidence and Progression of Age-Related Macular Degeneration in a National United States Database.},
journal = {American journal of ophthalmology},
volume = {280},
number = {},
pages = {458-471},
doi = {10.1016/j.ajo.2025.08.052},
pmid = {40885419},
issn = {1879-1891},
mesh = {Humans ; Male ; Female ; United States/epidemiology ; Retrospective Studies ; Incidence ; Disease Progression ; Aged ; Databases, Factual ; Middle Aged ; *Antidepressive Agents/therapeutic use/adverse effects ; *Wet Macular Degeneration/epidemiology/diagnosis/chemically induced ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; Propensity Score ; Risk Factors ; *Macular Degeneration/epidemiology ; Aged, 80 and over ; Antidepressive Agents, Tricyclic/therapeutic use ; },
abstract = {OBJECTIVE: To evaluate the association between antidepressant use and the risk of developing nonexudative and exudative age-related macular degeneration (AMD), as well as the progression from nonexudative to exudative AMD, in patients using selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs).<br><br>DESIGN: Retrospective clinical cohort study.<br><br>SUBJECTS: Patients aged &#x2265;40 years identified from the TriNetX database (October 2004-October 2023). Individuals were grouped based on exclusive use of SSRIs, SNRIs, or TCAs and compared to a control group without antidepressant use. Patients using multiple antidepressant classes were excluded.<br><br>METHODS: Propensity score matching (PSM) was applied to adjust for 17 confounders, including age, sex, smoking status, hypertension, and cardiovascular disease. The primary outcomes were the incidence of nonexudative AMD, exudative AMD, and progression from nonexudative to exudative AMD.<br><br>MAIN OUTCOME MEASURES: Risk ratios (RRs) comparing the incidence of nonexudative AMD, exudative AMD, and AMD progression in each antidepressant group versus matched controls.<br><br>RESULTS: After PSM, the analysis included 633 535 SSRI users, 826 404 SNRI users, and 501 873 TCA users. Compared to controls, antidepressant use was associated with a significantly reduced risk of nonexudative AMD (RR 0.606 for SSRIs; 0.141 for SNRIs; 0.234 for TCAs), exudative AMD (RR 0.733 for SSRIs; 0.161 for SNRIs; 0.267 for TCAs), and progression to exudative AMD (RR 0.701 for SSRIs; 0.665 for SNRIs; 0.676 for TCAs).<br><br>CONCLUSIONS: Use of SSRIs, SNRIs, or TCAs was associated with a lower risk of AMD onset and progression. Potential mechanisms include reduced inflammation, decreased oxidative stress, and neuroprotection via upregulation of brain-derived neurotrophic factors and suppression of proinflammatory cytokines. These findings are exploratory and hypothesis-generating, and further prospective and mechanistic studies are needed to better understand the relationship between antidepressant use and AMD pathophysiology.},
}
@article {pmid40885407,
year = {2026},
author = {Giannopoulos, NG and Macri, CZ and Seneviratne, IAK and Bacchi, S and Sun, MT and Chan, WO},
title = {A narrative review of the psychological impact of intravitreal injections.},
journal = {Survey of ophthalmology},
volume = {71},
number = {1},
pages = {179-188},
doi = {10.1016/j.survophthal.2025.08.017},
pmid = {40885407},
issn = {1879-3304},
mesh = {Humans ; *Intravitreal Injections/psychology/adverse effects ; *Anxiety/psychology/etiology ; *Retinal Diseases/drug therapy/psychology ; *Angiogenesis Inhibitors/administration &amp; dosage ; },
abstract = {Intravitreal injections (IVI) are a common, effective therapy for multiple retinal diseases although can be associated with significant psychological effects that reduce adherence to treatment. We reviewed the psychological impacts of IVI to characterise their causes, consequences, and solutions. We searched the electronic databases PubMed, OVID Medline, OVID Embase, Google Scholar and Cochrane Reviews and retrieved 1252 peer-reviewed articles. Thirty-four articles were ultimately included and analysed. The majority of retrieved articles pertained to anxiety; however, other impacts were also identified with limited available evidence regarding depression. Pre-procedural anxiety was generally mild to moderate and reported in 17.3-85 % of patients undergoing IVI. Key contributing factors to anxiety included a lack of patient education, pain and discomfort during the procedure, and travel and waiting times. Potential strategies to reduce anxiety included person-centred education, alternatives to speculum use, reducing clinic wait times, and music or handholding during the procedure. Patients experience significant anxiety from IVI, owing to multiple factors, including lack of education about the procedure, lack of procedural familiarity, and pain, which require a patient-centred approach to addressing that considers individual needs and preferences. Little data pertain to non-anxiety effects of IVI, and thus further research may identify additional barriers to adherence and their solutions.},
}
@article {pmid40881432,
year = {2025},
author = {Li, C and Lu, YC and Chen, MX},
title = {Cuproptosis-related signature and immune infiltration in age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {18},
number = {9},
pages = {1640-1649},
pmid = {40881432},
issn = {2222-3959},
abstract = {AIM: To investigate cuproptosis-related molecular and immune infiltration in age-related macular degeneration (AMD) development and establish a predictive model.<br><br>METHODS: The expression profiles of cuproptosis-related genes and immune signature in AMD based on the microarray dataset GSE29801 were analyzed. A total of 142 AMD samples were used to identify the cuproptosis-related differentially expressed genes (Cu-DEGs), together with the immune cell infiltration. To further refine the list of potential genes for AMD diagnosis, three machine learning techniques were used, and an external dataset were applied for confirming the accuracy of the predictive performance. Reverse transcription polymerase chain reaction (RT-PCR) were also performed to examine the level of mRNA of hub genes. The activated immune responses and Cu-DEGs were assessed between AMD and controls.<br><br>RESULTS: Six genes, including ATP7A, DBT, VEGFA, UBE2D3, CP, SLC31A1, were screened as cuproptosis-signature in AMD via three machine learning methods. Next, SLC31A1 and VEGFA was selected as hub genes by performance evaluation in an external dataset GSE160011, further analysis showed that SLC31A1 and VEGFA were associated with pathways related to immune signaling and immune function, which were then observed in relation to infiltrating immune cells. Finally, the mRNA expression levels of SLC31A1 and VEGFA were significantly higher in laser induced choroidal neovascularization (CNV) group than in control group detected by RT-PCR.<br><br>CONCLUSION: In this study, the possible relationship between cuproptosis and AMD is expounded systematically. A predictive model is developed to assess the risk of cuproptosis-related genes and their clinical prognostic value in AMD patients.},
}
@article {pmid40858941,
year = {2025},
author = {Hernandez, M and Romero-Vázquez, S and Recalde, S and Bezunartea, J and Orduña, MM and Belza-Zuazu, I and García-Layana, A and Adán, A and Fernández-Robredo, P and Molins, B},
title = {C-reactive protein dissociation drives choroidal neovascularization in age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {31408},
pmid = {40858941},
issn = {2045-2322},
support = {PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; PI19/00265//Instituto de Salud Carlos III/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD16/0008//Red Tem&#xe1;tica de Investigaci&#xf3;n Cooperativa en Salud, OFTARED/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; RD21/0017/0009//Advanced Therapies Network, RICORS-TERAV/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; SAF2016-81876-REDT//Red del complemento y Salud/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; Complemento 2-CM//Red del complemento de la Comunidad de Madrid/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD24/0007/0015//Carlos III Health Institute and co-financed by the European Union/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; RD21/0002/0010//Inflammatory Diseases Network, RICORS-REI/ ; },
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/etiology ; *C-Reactive Protein/metabolism/administration &amp; dosage ; *Macular Degeneration/metabolism/pathology ; Mice ; Female ; Male ; Disease Models, Animal ; Fluorescein Angiography ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/metabolism/pathology ; Humans ; Protein Isoforms/metabolism ; },
abstract = {Choroidal neovascularization (CNV) and inflammation play an important role in retinal disease development and the acute phase reactant C-reactive protein (CRP) has been shown to contribute to Age-related macular degeneration (AMD) in vitro. Our aim was to evaluate whether monomeric and pentameric CRP (pCRP, mCRP) isoforms contribute to CNV in vivo and to characterize the mechanism of CRP dissociation in-vivo and in vitro. Both CRP isoforms were intravitreally (IVT) or intravenously (IV) injected in mice, CNV was laser-induced, retinography and fluorescein angiography were performed to evaluate edema. Lectin, mCRP, F4/80 and C5b9 localization were assessed by immunofluorescence and visualized under a confocal microscope. CNV, intensity of fluorescence of mCRP (IF mCRP) was also quantified. To confirm pCRP dissociation in RPE cells and mice, pCRP was coupled to a fluorochrome and IVT injected. A statistical increase in CNV areas was observed in pCRP IVT injected males (p < 0.05) while a statistical decrease was shown in females (p < 0.05). After IV injection, pCRP males showed an increase in CNV areas only vs. mCRP injected mice (p < 0.05) and in females the injection of pCRP injected mice showed higher CNV areas vs. vehicle (p < 0.05) and vs. mCRP injected mice (p < 0.05). Retinal edema after IVT CRP injection was observed mainly in mCRP injected mice. In females there was an IF mCRP statistical decrease in pCRP IVT injected mice vs. vehicle and a statistical increase in pCRP IV injected mice vs. vehicle (p < 0.05). Mice injected with IVT isoforms showed F4/80 positive cells and C5b-9 deposition around the CNV areas. mCRP labeling was observed in the intercellular space of the endothelial cells in the angiogenic area and detected in pCRP IVT injected animals, demonstrating the dissociation of pCRP into mCRP both in vitro and in vivo in proinflammatory microenvironments. In conclusion, CRP administration increased the area of CNV and the edema observed in the subretinal space, suggesting that CRP is activated in the CNV inflammatory environment. In addition, we demonstrated that pCRP dissociates in vivo into mCRP in damaged areas close to CNV, hypothesizing that the CNV process is exacerbated by mCRP.},
}
@article {pmid40882639,
year = {2025},
author = {Farjood, F and Nandakumar, S and Bertucci, T and Kiehl, T and Lotz, S and Wang, Y and Black, J and Sai, S and Kozak, J and Arduini, BL and Temple, S and Boles, NC and Stern, JH},
title = {Single-cell transcriptome and surfaceome profiling of the adult human retinal pigment epithelium.},
journal = {Stem cell reports},
volume = {20},
number = {9},
pages = {102611},
pmid = {40882639},
issn = {2213-6711},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Single-Cell Analysis/methods ; *Transcriptome ; *Gene Expression Profiling ; Adult ; Cells, Cultured ; Biomarkers/metabolism ; },
abstract = {The retinal pigment epithelium (RPE) is a pigmented monolayer of cells beneath the neural retina that supports photoreceptor cell function essential for vision. Our study explores the diversity of adult human RPE subpopulations and associated implications for retinal biology. Employing cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), we identified distinct RPE cell subpopulations characterized by unique single-cell transcriptomic and surface protein signatures. Immunohistochemical analysis using CITE-seq markers demonstrated that different RPE subpopulations had previously unappreciated spatial patterns. Enrichment by CITE-seq surface marker selection revealed that different RPE subpopulations have distinct functions. By comparing native RPE cells isolated from the adult RPE layer to cultured RPE cells, we demonstrated that most RPE subpopulations were preserved during culture, a finding with relevance to an RPE cell product currently in clinical trial for treatment of non-exudative age-related macular degeneration. These findings deepen understanding of human RPE biology and provide valuable insights to optimize RPE-cell-based therapy.},
}
@article {pmid40882516,
year = {2025},
author = {Anitua, E and Reparaz, I and Alkhraisat, MH},
title = {Plasma rich in growth factors as a treatment for ocular fundus diseases: Mapping current applications and future directions.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {191},
number = {},
pages = {118440},
doi = {10.1016/j.biopha.2025.118440},
pmid = {40882516},
issn = {1950-6007},
mesh = {Humans ; *Intercellular Signaling Peptides and Proteins/administration &amp; dosage/therapeutic use ; *Retinal Diseases/therapy ; *Platelet-Rich Plasma ; Animals ; Fundus Oculi ; Treatment Outcome ; },
abstract = {Posterior segment diseases are a leading cause of irreversible blindness and remain challenging to treat with current therapies. Blood-derived products have emerged as promising regenerative tools due to their anti-inflammatory, neuroprotective, and regenerative properties. This review synthesizes evidence from 46 clinical studies published between 2019 and 2025, covering 1253 patients and 1570 eyes treated with platelet-rich derivatives for ocular fundus diseases. The most frequent indications were structural defects (59 %), inherited retinal dystrophies (11 %), optic neuropathies (11 %), age-related macular degeneration (7 %), and vascular dysfunctions (5 %). These therapies were administered via various routes, including intravitreal, subtenon, suprachoroidal, and subretinal injections, as well as eye drops and fibrin membranes. Across pathologies, platelet-derived therapies demonstrated high anatomical success rates, functional improvements, and low incidence of adverse events, most of which were transient and mild. Among the different formulations, plasma rich in growth factors (PRGF-Endoret®) stood out for its standardized preparation, immunosafe profile, and versatility in application. Despite promising clinical outcomes, heterogeneity in study designs, small sample sizes, and lack of standardized protocols limit generalizability. Further randomized controlled trials and mechanistic studies are needed to validate efficacy, define optimal formulations, and identify the patient populations most likely to benefit. Blood-derived products represent a promising therapeutic avenue in regenerative ophthalmology and may serve as effective adjuncts or alternatives in managing complex retinal and optic nerve disorders.},
}
@article {pmid40872771,
year = {2025},
author = {Ayala-Peña, VB},
title = {HSV-1 Infection in Retinal Pigment Epithelial Cells: A Possible Contribution to Age-Related Macular Degeneration.},
journal = {Viruses},
volume = {17},
number = {8},
pages = {},
pmid = {40872771},
issn = {1999-4915},
mesh = {*Herpesvirus 1, Human/physiology/pathogenicity ; Humans ; *Macular Degeneration/virology/pathology/metabolism ; *Retinal Pigment Epithelium/virology/pathology/metabolism ; *Herpes Simplex/virology/complications ; Animals ; Amyloid beta-Peptides/metabolism ; },
abstract = {Herpes simplex virus type 1 (HSV-1) is associated with eye infections. Specifically, the acute consequences of eye infections have been extensively studied. This review gathers information on possible collateral damage caused by HSV-1 in the retina, such as age-related macular degeneration (AMD), a neurodegenerative disease. The synthesis and accumulation of Amyloid-β peptide (Aβ) is a key hallmark in these types of pathologies. AMD is a disease of multifactorial origin, and viral infections play an important role in its development. It is known that once this virus has entered the eye, it can infect adjacent cells, thus having the ability to infect almost any cell type with great tropism. In the retina, retinal pigment epithelial (RPE) cells are primarily involved in AMD. This work reviews publications that show that RPE can produce Aβ, and once they are infected by HSV-1, the release is promoted. Also, all the information available in the literature that explains how these events may be interconnected has been compiled. This information is valuable when planning new treatments for multifactorial neurodegenerative diseases.},
}
@article {pmid40869227,
year = {2025},
author = {Klusek, K and Kijowska, M and Kiełbus, M and Sławińska, J and Kuźmiuk, D and Chorągiewicz, T and Rejdak, R and Dolar-Szczasny, J},
title = {The Supportive Role of Plant-Based Substances in AMD Treatment and Their Potential.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
pmid = {40869227},
issn = {1422-0067},
mesh = {Humans ; *Macular Degeneration/drug therapy/metabolism ; *Antioxidants/therapeutic use/pharmacology ; Animals ; Oxidative Stress/drug effects ; Anti-Inflammatory Agents/therapeutic use/pharmacology ; Curcumin/therapeutic use ; Polyphenols/therapeutic use/pharmacology ; Anthocyanins/therapeutic use/pharmacology ; },
abstract = {There is growing interest in the use of natural plant-derived compounds, such as polyphenols (including curcumin), flavonoids, silymarin, anthocyanins, lutein, and zeaxanthin, for the treatment of age-related macular degeneration (AMD). These substances exhibit antioxidant, anti-inflammatory, and protective effects on retinal cells, contributing to the preservation of retinal integrity by modulating the key pathogenic mechanisms of AMD, including oxidative stress, chronic inflammation, and pathological neovascularization. Consequently, they hold potential to support conventional therapeutic approaches and slow disease progression. Current studies highlight their promising role as adjunctive agents in AMD management. This literature review provides a comprehensive analysis of the potential role of the aforementioned natural plant-derived compounds in the prevention and supportive treatment of age-related macular degeneration. It also discusses their natural sources, modes of administration and supplementation, and highlights the importance of a nutrient-rich diet as a key factor in maintaining ocular health. Furthermore, the review synthesizes current scientific knowledge on the ability of natural antioxidants to slow the progression of AMD and outlines future research directions aimed at improving diagnostic methods and developing more effective preventive and therapeutic strategies.},
}
@article {pmid40868995,
year = {2025},
author = {Grupenmacher, AT and Augusto, BO and Fetter, BZ and Rocha, JP and Araujo, DL and Kniggendorf, V and Nader, HB and Regatieri, CVS and Dreyfuss, JL},
title = {Antiangiogenic Activity of 6-O-Desulfated Modified Heparin: Suppression of Choroidal Neovascularization.},
journal = {International journal of molecular sciences},
volume = {26},
number = {16},
pages = {},
pmid = {40868995},
issn = {1422-0067},
support = {2015/03964-6//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 421697/2021-0//National Council for Scientific and Technological Development/ ; },
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; *Heparin/pharmacology/chemistry/analogs &amp; derivatives/therapeutic use ; *Angiogenesis Inhibitors/pharmacology/chemistry/therapeutic use ; Rats ; Humans ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Rats, Zucker ; Disease Models, Animal ; Fibroblast Growth Factor 2/metabolism ; Macular Degeneration/drug therapy ; Human Umbilical Vein Endothelial Cells ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide, primarily due to pathological choroidal neovascularization (CNV). Our study investigates a chemically modified heparin derivative as a novel strategy to selectively modulate angiogenic signaling, offering a reduced anticoagulant risk and preclinical support for AMD treatment. We explored the therapeutic potential of 6-O-desulfated heparin (Hep-6Od) as an antiangiogenic agent with diminished anticoagulant activity. Synthesized via selective 6-O-desulfation and characterized using nuclear magnetic resonance (NMR), Hep-6Od demonstrated safety in retinal pigment epithelial cells with no cytotoxic effects at various concentrations. In vitro, the compound significantly inhibited endothelial cell proliferation, migration, and capillary tube formation. Differential scanning fluorimetry (DSF) assays confirmed molecular interaction between Hep-6Od and fibroblast growth factor 2 (FGF-2), suggesting interference with pro-angiogenic signaling pathways. In vivo, a laser-induced CNV model in lean Zucker rats showed a dose-dependent reduction in neovascular lesion areas after an intravitreal Hep-6Od injection. Compared to unfractionated heparin, Hep-6Od exhibited reduced anticoagulant effects in PT and aPTT assays while maintaining robust antiangiogenic properties. These findings support Hep-6Od as a promising alternative to anti-vascular endothelial growth factor (VEGF) therapies for AMD treatment, potentially expanding current retinal vascular disease interventions. The results underscore its potential to transform AMD management, pending further clinical validation and awaiting confirmation in further studies.},
}
@article {pmid40867892,
year = {2025},
author = {Chaudhary, S and Moon, J and Hu, Z and Kriukov, E and Pestun, S and Baranov, PY and Ng, YE and D'Amore, PA},
title = {The Mechanism of PMC (2,2,5,7,8-Pentamethyl-6-chromanol), a Sterically Hindered Phenol Antioxidant, in Rescuing Oxidized Low-Density-Lipoprotein-Induced Cytotoxicity in Human Retinal Pigment Epithelial Cells.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
pmid = {40867892},
issn = {2076-3921},
support = {P30EYE003790/EY/NEI NIH HHS/United States ; },
abstract = {Geographic atrophy or late-stage dry age-related macular degeneration (AMD) is characterized by drusen deposition and progressive retinal pigment epithelium (RPE) degeneration, leading to irreversible vision loss. The formation of drusen leads to dyshomeostasis, oxidative stress, and irreversible damage to the RPE. In this study, we used an in vitro model of oxidized low-density lipoprotein (ox-LDL)-induced human RPE damage/death to investigate the mechanism through which a sterically hindered phenol antioxidant compound, PMC (2,2,5,7,8-pentamethyl-6-chromanol), protects the RPE against ox-LDL-induced damage. We show that PMC exerts its protective effect by preventing the upregulation of stress-responsive heme oxygenase-1 (HMOX1/HO-1) and NAD(P)H: quinone oxidoreductase (NQO1) at the mRNA and protein levels. This effect was due to PMC's blockade of ROS generation, which in turn blocked nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, ultimately preventing the upregulation of antioxidant response elements (AREs), including HMOX1 and NQO1. The key role of HO-1 was demonstrated when the protective effect of PMC was inhibited by the knockdown of HMOX1. Additionally, PMC treatment under different experimental conditions and at different time points revealed that the continuous presence of PMC is required for the optimal protection against ox-LDL-induced cytotoxicity, defining the cellular pharmacokinetics of this molecule. Our data demonstrate the involvement of a key antioxidant pathway through which PMC mitigates the oxidative stress induced by ox-LDL and provides a potential therapeutic strategy for suppressing RPE degeneration/damage during AMD progression.},
}
@article {pmid40867647,
year = {2025},
author = {Maceroni, E and Cimini, A and Quintiliani, M and d'Angelo, M and Castelli, V},
title = {Retinal Gatekeepers: Molecular Mechanism and Therapeutic Role of Cysteine and Selenocysteine.},
journal = {Biomolecules},
volume = {15},
number = {8},
pages = {},
pmid = {40867647},
issn = {2218-273X},
mesh = {Humans ; *Selenocysteine/metabolism ; *Cysteine/metabolism ; Animals ; *Retina/metabolism/pathology/drug effects ; Oxidative Stress/drug effects ; Oxidation-Reduction ; Antioxidants/metabolism ; *Retinal Degeneration/metabolism/drug therapy ; Reactive Oxygen Species/metabolism ; },
abstract = {Oxidative stress is a key contributor to retinal degeneration, as the retina is highly metabolically active and exposed to constant light stimulation. This review explores the crucial roles of cysteine and selenocysteine in redox homeostasis and retinal protection. Cysteine, primarily synthesized via the transsulfuration pathway, is the rate-limiting precursor for glutathione (GSH), the most abundant intracellular antioxidant. Selenocysteine enables the enzymatic activity of selenoproteins, particularly glutathione peroxidases (GPXs), which counteract reactive oxygen species (ROS). Experimental evidence from retinal models confirms that depletion of cysteine or selenocysteine results in impaired antioxidant defense and photoreceptor death. Furthermore, dysregulation of these amino acids contributes to the pathogenesis of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Therapeutic approaches including N-acetylcysteine, selenium compounds, and gene therapy targeting thioredoxin systems have demonstrated protective effects in preclinical studies. Targeting cysteine and selenocysteine-dependent systems, as well as modulating the KEAP1-NRF2 pathway, may offer promising strategies for managing retinal neurodegeneration. Advancing our understanding of redox mechanisms and their role in retinal cell viability could unlock new precision treatment strategies for retinal diseases.},
}
@article {pmid40867611,
year = {2025},
author = {Chen, Q and Zhang, T and Chen, Z and Zeng, J and O'Connor, A and Zhu, M and Gillies, MC and Lu, F and Zhu, L},
title = {Retinal Pigment Epithelium Transplantation in Retinal Disease: Clinical Trial Development, Challenges, and Future Directions.},
journal = {Biomolecules},
volume = {15},
number = {8},
pages = {},
pmid = {40867611},
issn = {2218-273X},
support = {82201212//National Natural Science Foundation of China/ ; Not//the Claffy Foundation Bright Idea Grant/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/transplantation ; Clinical Trials as Topic ; *Macular Degeneration/therapy ; *Retinal Diseases/therapy ; Animals ; },
abstract = {Replacement of the retinal pigment epithelium (RPE) is emerging as a promising approach to treat degenerative retinal diseases, including age-related macular degeneration and Stargardt disease, in which RPE function cannot otherwise be restored. Despite the limitations of existing treatments, advances in cell sourcing and surgical methods have enabled initial human trials of RPE transplantation, with early results indicating potential efficacy. This review comprehensively examines the evolution of RPE transplantation in recent decades, highlighting the advantages and limitations of different cell sources and delivery methods. Current clinical trial data are analyzed with a particular focus on immune rejection risks, surgical complications, and long-term safety. Despite encouraging safety profiles, achieving consistent and sustained visual improvement remains a challenge, as vision outcomes might be influenced by factors such as disease stage at intervention, transplantation site, number of cells transplanted, and duration of follow-up. Key challenges, such as cell or graft survival and integration with the host retina, are discussed in depth, as overcoming these obstacles is essential for achieving stable and effective RPE replacement. Future research directions, including innovations in biomaterials, molecular modification strategies, and personalized approaches, hold promise for enhancing the efficacy and durability of RPE transplantation for retinal disease.},
}
@article {pmid40867504,
year = {2025},
author = {Hussain, AA and Lee, Y},
title = {Extracellular Matrix (ECM) Aging in the Retina: The Role of Matrix Metalloproteinases (MMPs) in Bruch's Membrane Pathology and Age-Related Macular Degeneration (AMD).},
journal = {Biomolecules},
volume = {15},
number = {8},
pages = {},
pmid = {40867504},
issn = {2218-273X},
mesh = {*Bruch Membrane/pathology/metabolism ; Humans ; *Macular Degeneration/metabolism/pathology ; *Matrix Metalloproteinases/metabolism ; *Extracellular Matrix/metabolism/pathology ; Animals ; *Aging/metabolism/pathology ; *Retina/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; },
abstract = {The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted as pro-forms and require activation to degrade ECM components. Their activity is modulated by tissue inhibitors of metalloproteinases (TIMPs). Aging disrupts this balance, leading to the accumulation of oxidized, cross-linked, and denatured matrix proteins, thereby impairing ECM function. Bruch's membrane, a penta-laminated ECM structure in the eye, plays a critical role in supporting photoreceptor and retinal pigment epithelium (RPE) health. Its age-related thickening and decreased permeability are associated with impaired nutrient delivery and waste removal, contributing to the pathogenesis of age-related macular degeneration (AMD). In AMD, MMP dysfunction is characterized by the reduced activation and sequestration of MMPs, which further limits matrix turnover. This narrative review explores the structural and functional changes in Bruch's membrane with aging, the role of MMPs in ECM degradation, and the relevance of these processes to AMD pathophysiology, highlighting emerging regulatory mechanisms and potential therapeutic targets.},
}
@article {pmid40833326,
year = {2025},
author = {Roberts, PA and Thomas, CN and Bellamy Plaice, G and Roberts, JA and Jones, MC and Andrews, JW and Hill, LJ},
title = {Mathematical Models of Topically and Intravitreally Applied Ranibizumab.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {45},
pmid = {40833326},
issn = {1552-5783},
mesh = {Ranibizumab/administration &amp; dosage/pharmacokinetics ; Animals ; Swine ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/pharmacokinetics ; Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; *Vitreous Body/metabolism ; Administration, Topical ; Aqueous Humor/metabolism ; *Models, Theoretical ; Enzyme-Linked Immunosorbent Assay ; Disease Models, Animal ; Wet Macular Degeneration/drug therapy/metabolism ; },
abstract = {PURPOSE: Wet age-related macular degeneration (AMD) causes vision loss when vascular endothelial growth factor (VEGF) stimulates blood vessel growth into the light-sensitive retina. Anti-VEGF treatments such as ranibizumab are currently administered to treat wet AMD via intravitreal injections, which are unpleasant, expensive, and risk complications. We explored the efficacy of topically administered ranibizumab, with cell-penetrating peptides (CPPs).<br><br>METHODS: Ex vivo pig eyes were divided into three groups and treated with (1) topical or (2) intravitreal ranibizumab and CPP, or (3) intravitreal ranibizumab. ELISAs measured ranibizumab and VEGF concentrations in the aqueous and vitreous at 20&#xa0;min, 40&#xa0;min, 1 h, and 3.5 h (n = 3, per group). An ordinary differential equation&#xa0;model was formulated to describe the evolving concentrations of ranibizumab, VEGF, and their compounds in the tear, aqueous, and vitreal compartments.<br><br>RESULTS: Experimental-Topical: aqueous ranibizumab levels increased significantly, coincident with a significant drop in aqueous VEGF. Vitreal ranibizumab increased significantly, while vitreal VEGF remained constant. Intravitreal (with and without CPP): vitreal ranibizumab reached high concentrations, coincident with a significant drop in vitreal VEGF. Mathematical-topical treatment may provide sustained, moderate suppression of vitreal VEGF levels, while intravitreal treatment provides strong suppression, which lessens between treatments.<br><br>CONCLUSIONS: CPP allows topical ranibizumab to penetrate the cornea. Combined intravitreal/topical treatment presents a promising approach; topical treatment suppresses vitreal VEGF levels between injections and thereby potentially reduces the frequency of injections. Treatment efficacy would be enhanced if ranibizumab's rate of binding to VEGF or tear residence time could be increased.},
}
@article {pmid40881439,
year = {2025},
author = {Gong, YJ and Zou, ZL and Qiu, KR and Wang, Q and Zhou, XL},
title = {Integration of multi-omics data reveals dysregulated RNA methylation in retinal pigment epithelium drives age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {18},
number = {9},
pages = {1626-1639},
pmid = {40881439},
issn = {2222-3959},
abstract = {AIM: To investigate the role of RNA methylation in retinal pigment epithelial (RPE) cells in age-related macular degeneration (AMD).<br><br>METHODS: RNA methylation-related gene expression profiles of AMD patient and normal control retinal pigment epithelium were evaluated by single-cell transcriptome from 34 samples (11 from normal donors and 23 from AMD patients). The causal relationship between RNA methylation dysfunction and AMD was analyzed by summary-data-based Mendelian randomization (SMR) using AMD GWAS data and multi-omics quantitative trait loci (QTL), including expression QTLs (eQTLs), protein QTLs (pQTLs), splicing QTLs (sQTLs), and m[6]A-QTLs (mQTLs). Additionally, machine learning models were applied to validate the causal association between RNA methylation dysfunction and AMD using Bulk RNA sequencing data from 31 normal donors and 37 AMD patients.<br><br>RESULTS: The single-cell transcriptome data analysis revealed massive dysregulation of RNA methylation-related gene expression in the RPE of AMD patients. SMR revealed causal associations between key RNA methylation regulators (METTL3, NSUN6, and MRM1, etc.) and AMD onset. Machine learning models further validated these findings and demonstrated a high accuracy of AMD risk prediction by using the above-identified RNA methylation-related genes: METTL3, NSUN6, and MRM1. Furthermore, METTL3 and NSUN6 were found to have a protective effect, while MRM1 was associated with an increased risk of AMD.<br><br>CONCLUSION: The results reveal the implication of dysregulation of RNA methylation-related gene expression in the RPE of AMD patients and further demonstrated a causal association between RNA methylation-related genes (METTL3, NSUN6, and MRM1) and AMD. These findings highlight the importance of RNA methylation in the pathogenesis of AMD and offer potential biomarkers and therapeutic targets for AMD management.},
}
@article {pmid40881438,
year = {2025},
author = {Yang, ZR and Li, C and Xing, DJ and Wei, GX and Zhao, CC and Zhou, M and Ma, XH and Zhao, Y and Yang, S and Yu, RG and Li, ZQ},
title = {Exploring the role of hyperreflective walls as a biomarker for the management of cystoid macular edema.},
journal = {International journal of ophthalmology},
volume = {18},
number = {9},
pages = {1697-1704},
pmid = {40881438},
issn = {2222-3959},
abstract = {AIM: To investigate the prevalence and clinical implications of hyperreflective walls (HRW) in foveal cystoid spaces in patients with cystoid macular edema (CME) caused by retinal diseases and noninfectious uveitis (NIU).<br><br>METHODS: This retrospective cross-sectional study included 443 eyes with CME secondary to diabetic macular edema (DME), retinal vein occlusion (RVO), retinitis pigmentosa (RP), neovascular age-related macular degeneration (nAMD), and NIU. Demographic data, HRW features, and other spectral domain optical coherence tomography (SD-OCT) biomarkers were analyzed.<br><br>RESULTS: HRW was observed in 40.9% of DME eyes (present, n=77, 38 males, 58.30&#xb1;12.04y; absent, n=111, 50 males, 55.95&#xb1;10.56y), 32.5% of RVO eyes (present, n=49, 22 males, 64.53&#xb1;11.90y; absent, n=102, 42 males, 60.67&#xb1;11.73y), 31.4% of nAMD eyes (present, n=16, 8 males, 70.13&#xb1;7.75y; absent, n=35, 13 males, 73.91&#xb1;9.11y), 57.1% of RP eyes (present, n=12, 4 males, 40.50&#xb1;12.06y; absent, n=9, 4 males, 44.11&#xb1;14.32y), and 18.8% of uveitic macular edema (UME) eyes (present, n=6, 3 males, 30.83&#xb1;16.23y; absent, n=26, 12 males, 43.46&#xb1;17.58y). HRW was significantly associated with vitreoretinal abnormalities [odds ratio (OR), 2.202; 95% confidence interval (95%CI), 1.342-3.613; P=0.002], hyperreflective foci (OR, 3.33; 95%CI, 1.884-5.883; P<0.001), inner retinal layer disorganization (OR, 1.816; 95%CI, 1.087-3.035; P=0.023), external limiting membrane disruptions (OR, 3.476; 95%CI, 1.839-6.574; P<0.001), and disrupted ellipsoid zone length (OR, 1.001; 95%CI, 1.000-1.002; P=0.04), and a high HRW height in the foveal cystoid spaces (OR, 1.003; 95%CI, 1.001-1.006; P=0.003).<br><br>CONCLUSION: HRW in foveal cystoid spaces is a common OCT finding in CME and is associated with more severe retinal structural damage and worse visual acuity. HRW may be utilized as a prognostic OCT biomarker for disease severity and treatment response in patients with CME. This study suggests that early detection of HRW and optimization of treatment strategies may improve patient prognosis.},
}
@article {pmid40880799,
year = {2025},
author = {Zingale, GA and Pandino, I and Trivellato, D and Cavaterra, D and Munari, F and Grasso, G and Bell, PA and Oddone, F and Bocedi, A and Coletta, M and Assfalg, M and D'Onofrio, M and Tundo, GR and Sbardella, D},
title = {SpectraSage unveils specific proteolytic patterns of 20S on mono-ubiquitylated Tau proteoforms involved in neurodegeneration.},
journal = {Chemical science},
volume = {16},
number = {36},
pages = {16979-16992},
pmid = {40880799},
issn = {2041-6520},
abstract = {The ubiquitin proteasome system is a critical regulator of proteostasis and shows altered activity and composition in neurodegenerative diseases affecting both the brain (e.g., Alzheimer's disease) and the retina/optic nerve (e.g., age-related macular degeneration, glaucoma). A common feature of neurodegeneration is the progressive accumulation of amyloidogenic proteins such as beta-amyloid and tau protein (MAPT gene). There is compelling evidence that the aggregation propensity of tau protein is regulated by post-synthetic modifications including phosphorylation and ubiquitylation. These alterations are gaining increasing pathological relevance not only for brain tauopathies but also for the retinal/optic nerve degenerative diseases. In this regard, site-specific mono-ubiquitylated (Ub) tau proteoforms, have been recently identified in neurodegenerative brains. In this work, the cleavage patterns of the uncapped 20S proteasome acting on mono-Ub regio-isomers of tauK18, which covers the 4RD domain, have been unveiled by using SpectraSage, a novel proteomics software conceived for the MS1 identification of complex branched peptide and here introduced for the first time. Ub position was found to affect regio-isomers susceptibility to proteolysis and unexpectedly long Ub-tauK18 branched peptides have been identified, proving distinct catalytic preferences. These findings show that the 20S digests mono-Ub proteins through specific enzymatic mechanisms and the implications of the latter on neurodegeneration are discussed.},
}
@article {pmid40876598,
year = {2025},
author = {Korobelnik, JF and Lanzetta, P and Leal, S and Holz, FG and Clark, WL and Eichenbaum, D and Iida, T and Sun, X and Berliner, AJ and Schulze, A and Zhao, M and Schmelter, T and Schmidt-Ott, U and Zhang, X and Morgan-Warren, P and Hasanbasic, Z and Vitti, R and Chu, KW and Reed, K and Bhore, R and Cheng, Y and Bai, Z and Hirshberg, B and Yancopoulos, GD and Wong, TY and , },
title = {Intravitreal Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration: Ninety-Six-Week Results from the Randomized Phase 3 PULSAR Trial.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2025.08.022},
pmid = {40876598},
issn = {1549-4713},
abstract = {PURPOSE: To report the efficacy, durability, and safety of intravitreal aflibercept 8 mg versus intravitreal aflibercept 2 mg every 8 weeks (2q8) in patients with neovascular age-related macular degeneration (nAMD) through 96 weeks, PULSAR (ClinicalTrials.gov identifier, NCT04423718).<br><br>DESIGN: Phase 3, randomized, noninferiority, 96-week trial.<br><br>PARTICIPANTS: Treatment-naive adults &#x2265; 50 years with nAMD.<br><br>METHODS: Patients were randomized 1:1:1 to intravitreal aflibercept 8 mg every 12 or 16 weeks (8q12 or 8q16), or 2q8, after 3 initial monthly doses; dosing intervals in 8-mg groups were modified based on prespecified criteria.<br><br>MAIN OUTCOME MEASURES: Change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), proportion of patients maintaining or extending the randomized dosing intervals, and safety outcomes.<br><br>RESULTS: Of 1009 patients treated, 869 patients (8q12, n = 291; 8q16, n = 292; 2q8, n = 286) completed treatment through week 96. Least squares (LS) mean change from baseline in BCVA at week 96 was +5.6 (95% confidence interval [Cl], 4.1-7.1), +5.5 (95% Cl, 4.0-7.0), and +6.6 (95% Cl, 5.2-8.0) letters in the 8q12, 8q16, and 2q8 groups, respectively; 8q12 and 8q16 differences versus 2q8 in LS mean BCVA changes at week 96 met the noninferiority criteria specified for the primary end point at week 48. Mean (standard deviation) change in CRT from baseline was -143.9 (123.6) &#x3bc;m, -153.4 (140.8) &#x3bc;m, and -135.8 (133.1) &#x3bc;m in the 8q12, 8q16, and 2q8 groups, respectively. Patients completing 96 weeks of treatment in the 8q12, 8q16, and 2q8 groups received a mean of 9.7, 8.2, and 12.8 active injections, respectively. Of these, 87% of patients in the 8q12 group had last assigned dosing intervals of 12 weeks or more, whereas 78%, 53%, and 31% of patients in the 8q16 group qualified for last assigned dosing intervals of &#x2265; 16 weeks, &#x2265; 20 weeks, and 24 weeks, respectively. Incidence of ocular treatment-emergent adverse events was similar across groups.<br><br>CONCLUSIONS: Aflibercept 8 mg delivered sustained disease control in patients with nAMD, maintaining improvements in visual and anatomic outcomes through week 96 with extended dosing intervals and similar safety profile to aflibercept 2 mg.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40876568,
year = {2025},
author = {Gao, J and Luo, T and Qu, W and Wang, W and Mo, Y},
title = {Potential role of endoplasmic reticulum quality control in retinal degenerative diseases.},
journal = {Neuroscience},
volume = {587},
number = {},
pages = {27-37},
doi = {10.1016/j.neuroscience.2025.08.052},
pmid = {40876568},
issn = {1873-7544},
mesh = {Humans ; *Endoplasmic Reticulum/metabolism ; Animals ; *Endoplasmic Reticulum Stress/physiology ; *Retinal Degeneration/metabolism/pathology ; Endoplasmic Reticulum-Associated Degradation/physiology ; Autophagy/physiology ; },
abstract = {The endoplasmic reticulum (ER) is the largest organelle in eukaryotic cells, and it plays a crucial role in regulating various biological processes, including protein folding, translation, and structural maturation. Accurate protein modification is essential for maintaining oxidative stress, apoptosis, and cellular senescence in the organism. The regulation of protein homeostasis involves three biological processes: endoplasmic reticulum stress (ERS), endoplasmic reticulum autophagy (ERPA), and endoplasmic reticulum-associated degradation (ERAD). Retinal degenerative disease (RDD) is a blinding eye conditions that cause severe vision loss. Although the pathogenesis of RDD is complex, previous data suggest that ER plays a key role in the development of a variety of eye diseases, such as diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), and axial myopia. Based on this, this paper will review the process of endoplasmic reticulum quality control (ERQC) and summarize the pathological mechanisms of the aforementioned eye diseases from the perspective of ERQC, providing new insights for the treatment of RDD.},
}
@article {pmid40838944,
year = {2025},
author = {Berlin, A and Goerdt, L and Clark, ME and Gao, L and Swain, TA and McGwin, G and Owsley, C and Sloan, KR and Curcio, CA},
title = {Advanced Analysis Tools for Two Wavelength Autofluorescence Imaging of Macular Xanthophyll Carotenoids: ALSTAR2 Baseline.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {8},
pages = {32},
pmid = {40838944},
issn = {2164-2591},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Adult ; Female ; Humans ; Male ; Young Adult ; Algorithms ; *Carotenoids ; *Macula Lutea/diagnostic imaging/metabolism ; *Macular Degeneration/metabolism/diagnostic imaging ; *Macular Pigment/metabolism ; *Optical Imaging/methods ; Tomography, Optical Coherence/methods ; *Xanthophylls/metabolism ; },
abstract = {PURPOSE: To allow exploration of xanthophyll carotenoids in vision and age-related macular degeneration progression using two-wavelength autofluorescence imaging for macular pigment optical density (MPOD), we developed tools for automatically centering and classifying the MPOD distribution pattern.<br><br>METHODS: A subset of the ALSTAR2 baseline cohort (NCT04112667) and 44 eyes of adults aged 20 to 30 years with healthy maculas were imaged with optical coherence tomography and two-wavelength autofluorescence (MPOD module, Heidelberg Engineering). Images underwent a quality review. Two custom FIJI plugins centered the MPOD distribution by five algorithms (FOVEA, HILLCLIMB, CENTROID, MAX, CONTOUR). Others automatically classified spatial distributions into four patterns from Obana et al: Peak, Ring, Mixed, and Dip.<br><br>RESULTS: Of 651 qualifying aged eyes and 44 young eyes, the HILLCLIMB and CONTOUR methods best agreed with a manually determined foveal center. Regarding spatial distribution pattern, 445 aged eyes (68.4%) showed peaks, 118 (18.1%) rings, 41 (6.3%) mixed, and 47 (7.2%) dips. In young eyes, 40 (90%) showed peaks, 1 (2.3%) rings, 3 (6.8%) mixed, and none showed dips. Notably, peaks were significantly (P&#xa0;<&#xa0;0.001) more prominent in men (74.1%) than women (65.0%) and pseudophakic (72.7%) than phakic (62.9%) eyes.<br><br>CONCLUSIONS: Automatic tools for MPOD centration are reliable and robust. Future studies will use the HILLCLIMB and CONTOUR algorithms.<br><br>TRANSLATIONAL RELEVANCE: Automated MPOD pattern assignment suggests that the spatial distribution of MPOD varies with gender, lens status, and possibly age. Our analytic software can be applied to large samples for studies of xanthophyll carotenoid impact on vision and age-related macular degeneration progression.},
}
@article {pmid40875052,
year = {2025},
author = {Hikichi, T and Kurabe, H and Notoya, A and Oguro, Y and Hirano, M and Doi, Y},
title = {Morphologic changes of the double-layer sign during anti-vascular endothelial growth factor therapy in eyes with neovascular age-related macular degeneration.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {363},
pmid = {40875052},
issn = {1573-2630},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Female ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage ; Fluorescein Angiography/methods ; *Visual Acuity ; Follow-Up Studies ; Aged, 80 and over ; Fundus Oculi ; *Bevacizumab/administration &amp; dosage ; *Macula Lutea/pathology ; },
abstract = {PURPOSE: To evaluate longitudinal morphologic changes of the double-layer sign (DLS) on optical coherence tomography (OCT) in eyes with neovascular age-related macular degeneration (nAMD) presenting with exudative macular neovascularization (eMNV) undergoing anti-vascular endothelial growth factor (VEGF) therapy.<br><br>METHODS: This retrospective study included 207 consecutive treatment-na&#xef;ve eyes (207 patients) with nAMD presenting with eMNV and a DLS treated with intravitreal anti-VEGF injections and were followed for&#x2009;&#x2265;&#x2009;12&#xa0;months. All eyes received 3 monthly loading injections followed by either treat-and-extend (TAE) or pro re nata (PRN) retreatment, per predefined criteria. DLS area, length, and height were measured at baseline, after loading, and 12&#xa0;months.<br><br>RESULTS: All 207 eyes demonstrated significant reductions in mean&#x202f;(&#xb1;&#x2009;standard deviation) DLS area, length, and height 1&#xa0;month after the third monthly injection (165&#x2009;&#xb1;&#x2009;188&#xa0;&#xb5;m[2], 1446&#x2009;&#xb1;&#x2009;639&#xa0;&#xb5;m, and 202&#x2009;&#xb1;&#x2009;109&#xa0;&#xb5;m, respectively) compared with baseline (302&#x2009;&#xb1;&#x2009;264&#xa0;&#xb5;m[2], 1801&#x2009;&#xb1;&#x2009;573&#xa0;&#xb5;m, and 282&#x2009;&#xb1;&#x2009;150&#xa0;&#xb5;m, respectively) (P&#x2009;=&#x2009;0.001, P&#x2009;=&#x2009;0.001, and P&#x2009;=&#x2009;0.024, respectively). At 12&#xa0;months the mean change in DLS area was -&#xa0;141&#xa0;&#xb5;m[2] [95%&#x202f;confidence interval (CI) -&#xa0;185&#xa0;to -&#xa0;98], and median (95% CI) injection number was 8.1 (7.9 to 8.4). Eyes with subretinal and/or intraretinal fluid (SRF/IRF) at 12&#xa0;months showed re-enlargement of DLS parameters, whereas eyes without SRF/IRF maintained the post-treatment decrease.<br><br>CONCLUSION: DLS morphology regresses after anti-VEGF therapy, and persistent or recurrent fluid is associated with less durable regression. The DLS regresses in response to anti-VEGF therapy, and its behaviour correlates with the clinical course of exudative MNV associated with a DLS. DLS monitoring may complement-but not replace-multimodal imaging when assessing MNV activity.},
}
@article {pmid40874965,
year = {2025},
author = {Ono, T and Iwasaki, T and Sakisaka, T and Mori, Y and Nejima, R and Miyai, T and Miyata, K},
title = {Visual acuity and ocular comorbidities in patients aged 100 years and older: A retrospective, crosssectional study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {40874965},
issn = {1435-702X},
abstract = {PURPOSE: The centenarian population is increasing with an increase in global life expectancy. However, data on visual status and ocular diseases in this age group remain limited. We aimed to assess visual acuity and ocular comorbidities in patients aged ≥ 100 years.<br><br>METHODS: This retrospective cross-sectional study included patients aged&#x2009;&#x2265;&#x2009;100 years who visited Miyata Eye Hospital between January 2016 and December 2024. Data on best-corrected visual acuity (BCVA), intraocular pressure, and ocular comorbidities were extracted from medical records. Multivariate linear regression was performed to analyse the associations between BCVA and ocular diseases.<br><br>RESULTS: This study included 50 eyes of 25 patients. The mean age was 100.8&#x2009;&#xb1;&#x2009;1.0 years, and 80.0% of the eyes belonged to women. The mean BCVA was 1.01&#x2009;&#xb1;&#x2009;0.93 logarithm of the minimum angle of resolution. The most common ocular conditions were dry eye (54%), glaucoma (46%), cataract (40%), and macular degeneration (40%). Multivariate analysis revealed that cataract (p&#x2009;=&#x2009;0.019) and uveitis (p&#x2009;=&#x2009;0.003) were significantly linked to poor visual acuity.<br><br>CONCLUSION: Cataracts and uveitis were the most significant factors contributing to visual impairment in centenarian patients. Thus, an improved understanding of the ocular health status is crucial for maintaining visual function and quality of life in this unique population.},
}
@article {pmid40874774,
year = {2025},
author = {Magdum, R and Aher, PS and Pancholi, T and Chodvadiya, S and Kamdar, GA and Gupta, A and Gupta, A and Gupta, P},
title = {Optical Coherence Tomography Analysis of Macular Edema Across Disease Spectra.},
journal = {Annals of African medicine},
volume = {},
number = {},
pages = {},
doi = {10.4103/aam.aam_263_25},
pmid = {40874774},
issn = {0975-5764},
abstract = {INTRODUCTION: Macular edema (ME) is a leading cause of visual impairment associated with various retinal pathologies. Spectral-domain optical coherence tomography (SD-OCT) provides high-resolution imaging, allowing detailed assessment of ME patterns and structural changes.<br><br>AIM: The aim of this study was to evaluate the distribution and characteristics of ME across different etiologies using SD-OCT.<br><br>MATERIALS AND METHODS: This cross-sectional observational study included patients with ME from diverse etiologies. SD-OCT was used to assess central macular thickness, retinal volume, cystoid spaces (CS), epiretinal membrane (ERM), hyperreflective foci, and disorganization of retinal inner layers (DRIL).<br><br>RESULTS: A total of 54% of the study participants were female, with a mean age of 57 years. Diabetes mellitus (50.4%) was the most common etiology, followed by retinal vein occlusions, age-related macular degeneration, ERM, and inflammatory causes. CS were observed in 49.6% of cases, and DRIL in 48%. Severe visual impairment was more frequent in diabetic and vaso-occlusive cases.<br><br>CONCLUSION: SD-OCT effectively identifies structural patterns in ME across etiologies, assisting in diagnosis and management planning.},
}
@article {pmid40874294,
year = {2025},
author = {Kaźmierski, R},
title = {Age-related macular degeneration and risk of stroke: an unresolved issue.},
journal = {Neurologia i neurochirurgia polska},
volume = {59},
number = {4},
pages = {307-309},
doi = {10.5603/pjnns.104996},
pmid = {40874294},
issn = {0028-3843},
}
@article {pmid40873164,
year = {2025},
author = {Sharma, KK and Durgapal, S and Tyagi, SJ and Varshney, P and Kumar, G},
title = {Innovations in mRNA-Based Nanoparticle for the Treatment of Ocular Disorders: A Comprehensive Review.},
journal = {Current pharmaceutical design},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113816128391408250804231522},
pmid = {40873164},
issn = {1873-4286},
abstract = {The eye, due to its complex anatomy and physiology, presents numerous barriers that restrict the access of drug molecules to the site of action for the maintenance of optimal concentration. Thus, limited drug bioavailability is one of the significant issues with commercially existing drug delivery systems in achieving overall therapeutic effectiveness. Recently, the field of ocular health and management has garnered much attention for the innovation of efficient nanotechnology approaches to overcome the constraints imposed by the intricate anatomy and physiology of the eye. Hypothesizing that the conjugation of mRNA-based therapies with the latest nano delivery systems can overcome these barriers, this review was designed to explore the outstanding potential of these approaches for the management of ocular disorders. With extensive investigations of current findings, the authors believe that such integrations present exciting opportunities to pave the way for the development of effective approaches for various ocular disorders such as uveitis, Leber congenital amaurosis, age-related macular degeneration, retinitis pigmentosa, and many more. Moreover, the approaches exploiting the combination of mRNA and nanotechnology offer effective solutions to address the limitations of currently available management strategies. This review presents various innovative mRNA-based nanotechnology approaches, their mechanisms, challenges, and prospects for further development, focusing on the immense potential of mRNA-based strategies to revolutionize the landscape of ocular therapeutics.},
}
@article {pmid40869660,
year = {2025},
author = {Gwon, HN and Son, HJ and Shin, YJ},
title = {Association of Body Metrics and Ocular Diseases.},
journal = {Journal of clinical medicine},
volume = {14},
number = {16},
pages = {},
pmid = {40869660},
issn = {2077-0383},
support = {Hallym University Research Fund//Hallym University/ ; NRF-2023R1A2C2002674//National Research Foundation (NRF) grant by the Korea government/ ; },
abstract = {Background/Objectives: The relationship between systemic health and ocular diseases is well-documented, with various body metrics potentially playing significant roles in the pathogenesis of cataracts, glaucoma, and age-related macular degeneration (AMD). However, comprehensive studies linking these metrics with ocular health are sparse. This study aims to explore the associations between height, weight, waist circumference, and BMI with the prevalence and current status of cataracts, glaucoma, and AMD in a large cohort. Methods: We used data from Korean National Health and Nutrition Survey (KNHANES 2015-2021), a national, cross-sectional health examination and survey, for which representative data on the health, nutritional status, and physical activities of the Korean general population are collected by the Korea Centers for Disease Control and Prevention (KCDC). We compared height, weight, waist circumference, and BMI among patients with diagnosed and current cataracts, glaucoma, and AMD versus those without these conditions. Statistical analyses included t-tests and Pearson correlation analyses to examine the relationships between body metrics and ocular diseases. Results: Our findings indicate that shorter height and lower weight are associated with diagnosed cataracts and glaucoma but not with their current status. A greater waist circumference was observed in patients with diagnosed cataracts, glaucoma, and AMD compared to controls, suggesting central obesity as a potential associated factor. No significant differences in BMI were found in patients with current ocular diseases. Additionally, certain body metrics were correlated with refractive errors and visual acuity, suggesting broader implications for ocular health. Conclusions: The study highlights significant associations between body metrics and the risk of developing cataracts, glaucoma, and AMD. AMD was found to be more closely related to systemic diseases, such as diabetes and hypertension, than to body metrics. These findings suggest that interventions targeting obesity and metabolic health could potentially reduce the risk or severity of these common ocular conditions. Further research is needed to confirm these relationships and explore underlying mechanisms.},
}
@article {pmid40866110,
year = {2025},
author = {Airaldi, M and Parrulli, S and Trinco, A and Cinus, F and Staurenghi, G and Pellegrini, M and Cereda, M},
title = {Impact of a laminar air flow portable device on post-intravitreal injection endophthalmitis rate.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327316},
pmid = {40866110},
issn = {1468-2079},
abstract = {Intravitreal injections (IVIs) are the most common outpatient procedure worldwide, yet no consensus exists regarding their optimal setting. This study analysed 101 976 IVIs performed between 2017 and 2023, comparing endophthalmitis rates before and after introducing a mobile laminar air flow (LAF) device in a clean room. The incidence of endophthalmitis decreased from 0.033% to 0.013%, a 63.2% risk reduction (Odds Ratio=0.368, p=0.04). These findings suggest that mobile LAF enhances air quality and reduces infection risk, offering a cost-effective, efficient alternative to operating theatres for IVIs.},
}
@article {pmid40863488,
year = {2025},
author = {Qureshi, ADA and Malik, H and Naeem, A and Hassan, SN and Jeong, D and Naqvi, RA},
title = {ODDM: Integration of SMOTE Tomek with Deep Learning on Imbalanced Color Fundus Images for Classification of Several Ocular Diseases.},
journal = {Journal of imaging},
volume = {11},
number = {8},
pages = {},
pmid = {40863488},
issn = {2313-433X},
support = {NRF[2022-R1-G1A1(010226)]//National Research Foundation of Korea/ ; },
abstract = {Ocular disease (OD) represents a complex medical condition affecting humans. OD diagnosis is a challenging process in the current medical system, and blindness may occur if the disease is not detected at its initial phase. Recent studies showed significant outcomes in the identification of OD using deep learning (DL) models. Thus, this work aims to develop a multi-classification DL-based model for the classification of seven ODs, including normal (NOR), age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma (GLU), maculopathy (MAC), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR), using color fundus images (CFIs). This work proposes a custom model named the ocular disease detection model (ODDM) based on a CNN. The proposed ODDM is trained and tested on a publicly available ocular disease dataset (ODD). Additionally, the SMOTE Tomek (SM-TOM) approach is also used to handle the imbalanced distribution of the OD images in the ODD. The performance of the ODDM is compared with seven baseline models, including DenseNet-201 (R1), EfficientNet-B0 (R2), Inception-V3 (R3), MobileNet (R4), Vgg-16 (R5), Vgg-19 (R6), and ResNet-50 (R7). The proposed ODDM obtained a 98.94% AUC, along with 97.19% accuracy, a recall of 88.74%, a precision of 95.23%, and an F1-score of 88.31% in classifying the seven different types of OD. Furthermore, ANOVA and Tukey HSD (Honestly Significant Difference) post hoc tests are also applied to represent the statistical significance of the proposed ODDM. Thus, this study concludes that the results of the proposed ODDM are superior to those of baseline models and state-of-the-art models.},
}
@article {pmid40850787,
year = {2025},
author = {Cañizo-Outeiriño, A and Castro-Fernández, DC and Arias-Barquet, L and Fernández-Rodríguez, MI and Olivier-Pascual, N and Ortea, I and Pastor-Iodate, S and Rodríguez-De la Rúa-Franch, E and Ruiz-Moreno, JM and Ruiz-Moreno, &#xd3; and Sáenz de Viteri-Vázquez, M and Sala-Puigdollers, A and , and Fernández-Ferreiro, A},
title = {Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) study protocol.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40850787},
issn = {2397-3269},
mesh = {Humans ; *Precision Medicine/methods ; *Proteomics/methods ; Prospective Studies ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Biomarkers/metabolism ; *Wet Macular Degeneration/drug therapy/metabolism ; Intravitreal Injections ; Male ; Aged ; Female ; Macular Degeneration/drug therapy ; Observational Studies as Topic ; Multicenter Studies as Topic ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people over 55 years of age globally, being neovascular AMD (nAMD) its most aggressive form. Its treatment consists of the use of drugs that block vascular endothelial growth factor (anti-VEGF). Proteomics may allow the identification of differentially expressed proteins between responders and non-responders to each anti-VEGF drug. Thus, the objective of Pharmacoproteomics in the development of personalised medicine in Age-related Macular Degeneration (PHARPRO-AMD) is to find new proteomic biomarkers, predictive of response to antiangiogenic treatment in patients with nAMD.<br><br>METHODS AND ANALYSIS: PHARPRO-AMD is a nationwide, multicentre, prospective, observational study. Treatment-na&#xef;ve patients with nAMD starting anti-VEGF therapy will be enrolled and followed up for 2 years. During this period, clinical variables will be gathered to classify treatment response. In addition, blood, tear and vitreous and aqueous humour samples will be collected and will undergo a ZenoSWATH proteomic analysis. Relevant biomarkers identified and response classification will be used to perform a multivariate logistic regression and construct receiver operating characteristic curves.<br><br>RESULTS: The study is expected to identify a panel of proteomic biomarkers predictive of anti-VEGF treatment response. Integrating data from invasive and non-invasive biological samples may enhance clinical applicability. Once validated, these biomarkers could support the design of future clinical trials on biomarker-guided therapies, helping to optimise treatment regimens and improve visual outcomes.<br><br>CONCLUSIONS: The PHARPRO-AMD study aims to provide proof-of-concept for biomarker-guided anti-VEGF therapy in nAMD, potentially improving vision outcomes. A notable limitation is the exclusion of patients with visual acuity above 73 Early Treatment of Diabetic Retinopathy Study letters, a criterion chosen to reduce potential ceiling effects and improve response assessment accuracy.<br><br>ETHICS AND DISSEMINATION: Approved by the Galician Network of Ethics Committees, with nationwide validity. Anonymised data will be deposited in open-access repositories and published in peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBER: Spanish Clinical Studies Registry (REec) (0033-2024-OBS).},
}
@article {pmid40833323,
year = {2025},
author = {Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Bogunovic, H and Schmidt-Erfurth, U},
title = {Dynamics of the EZ/RPE Loss Ratio on OCT Over Time During Geographic Atrophy Progression and Treatment With Pegcetacoplan.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {48},
pmid = {40833323},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/drug therapy/diagnosis/etiology ; *Retinal Pigment Epithelium/pathology ; Disease Progression ; Aged ; Male ; Female ; Intravitreal Injections ; Prospective Studies ; Visual Acuity ; *Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Aged, 80 and over ; Fluorescein Angiography ; Deep Learning ; },
abstract = {PURPOSE: The purpose of this study was to investigate the change of ellipsoid zone (EZ)/retinal pigment epithelium (RPE) loss ratio on optical coherence tomography (OCT) in geographic atrophy (GA) secondary to age-related macular degeneration using deep learning-based analysis.<br><br>METHODS: OCT volumes of patients from the OAKS (NCT03525613) and DERBY (NCT03525600) trials, two phase III prospective randomized trials of GA treated with sham, intravitreal pegcetacoplan monthly (PM) and every other month (PEOM) were included. RPE and EZ loss were measured on OCT using validated deep learning-based algorithms. Pooled study eyes were divided into 4 quartiles determined by EZ/RPE loss ratios on OCT at baseline, month 12, and month 24. The change in ratio with treatment and its association with further disease progression and therapeutic response were analyzed.<br><br>RESULTS: Eight hundred eighty-nine OCT volumes were included. Overall, quartiles shifted downward at 12 and 24 months, representing a moderate decrease in disease activity, particularly in treated eyes. The EZ/RPE loss quartiles at month 12 were prognostic for further disease progression in the sham eyes for RPE and EZ loss. There was a higher likelihood of a quartile decrease in the PM and PEOM groups versus the sham at month 24 (P value quartile shift PM versus sham = 0.14, PEOM versus sham = 0.0053).<br><br>CONCLUSIONS: The change in EZ/RPE loss ratios at month 12 remained to be predictive for disease activity and therapeutic response, providing insights into disease mechanisms and relevant guidance for GA management in clinical practice. The EZ/RPE loss ratio decreased either due to advanced GA or induced by therapy in treated patients versus sham.},
}
@article {pmid40862502,
year = {2025},
author = {Kuo, D and Pajic, M and Hadziahmetovic, M},
title = {Ten years later: how is AI impacting retina care today?.},
journal = {Current opinion in ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICU.0000000000001167},
pmid = {40862502},
issn = {1531-7021},
support = {R21 EY033480/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE OF REVIEW: Artificial intelligence (AI) is transforming retina care, with deep learning (DL) models shaping a new era of improved screening accessibility, diagnostic precision, and personalized disease monitoring. This review highlights recent AI-powered clinical applications in diabetic retinopathy (DR), and age-related macular degeneration (AMD) care.<br><br>RECENT FINDINGS: Since the FDA's authorization of the first autonomous AI system for DR screening in 2018, multiple platforms have emerged, expanding access to diabetic eye care. Real-world studies have confirmed a significant improvement in screening adherence and diagnostic accuracy, illustrating AI's tangible impact on public health. Meanwhile, newly certified AI technologies that meet European regulatory standards are increasingly guiding clinical decision-making in the management of AMD and diabetic macular edema through automated analysis of optical coherence tomography (OCT) images. Most recently, FDA-authorized home OCT platforms are transforming AMD monitoring, enabling proactive and remote management of retinal fluid.<br><br>SUMMARY: As AI increasingly empowers patients and providers, its widespread success still depends on ongoing work, including thorough validation, outcome-based metrics, and improved workflow integration. The next decade will reveal whether AI in retina care transitions from a promising innovation to an essential and indispensable tool in modern retina.},
}
@article {pmid40862273,
year = {2025},
author = {Sezer, T and Altıkardeşler, E and Erdoğan, K and Arslan, B and Çolak, K},
title = {Evaluation of pain scores during intravitreal injection in systemic conditions and in conjunction with medications.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414241275360},
pmid = {40862273},
issn = {2515-8414},
abstract = {BACKGROUND: Intravitreal injection (IVI) is a common practice in today's ophthalmology clinics. The pain that patients will experience after the application may be important in compliance with the treatment.<br><br>OBJECTIVES: This study aimed to investigate the correlation between various clinical characteristics of patients receiving IVI and corresponding visual analogue scale (VAS) scores (0: no pain to 10: severe pain).<br><br>DESIGN: Single-centre, Prospective study.<br><br>METHODS: A total of 313 participants (168 females, 145 males) with a mean age of 66.91&#x2009;&#xb1;&#x2009;9.67&#x2009;years underwent IVI for diabetic retinopathy (DRP), retinal vein occlusion (RVO), or age-related macular degeneration (AMD). Eye examinations, including visual acuity and intraocular pressure measurements, were also conducted, and injection indications were determined based on dilated fundus examinations and spectral domain optical coherence tomography images. Following the injections, the researchers solicited VAS scores ranging from 0 to 10 (no pain to severe pain). The study explored the relationships between clinical characteristics, headache frequency, joint and muscle pain, analgesic use, surgical history, antidepressant use, vasovagal syncope, previous injections, and VAS score.<br><br>RESULTS: The mean VAS score was 4.77&#x2009;&#xb1;&#x2009;2.90. While DRP and RVO had similar VAS scores (4.95&#x2009;&#xb1;&#x2009;2.98 and 5.22&#x2009;&#xb1;&#x2009;2.70, respectively), the AMD group had significantly lower scores (4.09&#x2009;&#xb1;&#x2009;2.64). Compared with nonusers, antidepressant users had significantly greater VAS scores (5.79&#x2009;&#xb1;&#x2009;3.43) (4.52&#x2009;&#xb1;&#x2009;2.70) (p&#x2009;<&#x2009;0.05). Patients with a history of syncope had significantly greater VAS scores (p&#x2009;<&#x2009;0.05). In patients reporting monthly headaches, a positive correlation was found between headache frequency and VAS score (r&#x2009;=&#x2009;0.23, p&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: For individuals experiencing daily headaches, inquiries about vasovagal syncope and antidepressant use may be beneficial, considering the potential association of these symptoms with higher VAS scores after IVIs.},
}
@article {pmid40862026,
year = {2025},
author = {Rodrigues De Moura, M and Sasher, T and Smith, T},
title = {An Abnormal Presentation of Age-Related Macular Degeneration in a Young, Healthy Adult.},
journal = {Cureus},
volume = {17},
number = {8},
pages = {e90672},
pmid = {40862026},
issn = {2168-8184},
abstract = {Age-related macular degeneration (AMD) is a relatively uncommon diagnosis in patients under the age of 45. It typically manifests as a gradual or sudden loss of central vision, producing blurred images or wavy visual distortions. These symptoms can interfere not only with daily activities but also with more detailed visual tasks, significantly impacting quality of life. This case report illustrates the rare presentation of intermediate AMD in a 43-year-old male with no significant past medical history. The case also highlights the importance of maintaining routine health examinations, including annual primary care visits and baseline ophthalmologic examinations. Regular health screenings are vital for the early detection of potential diseases and are a crucial part of preventive medicine.},
}
@article {pmid40861593,
year = {2025},
author = {Gartaganis, P and Khamis, N and Hamoud Bedan, A and Driouich, Z and Ashraf, MO and Abucar Osman, S and Younis, S},
title = {A Comparative Assessment of Intraocular Pressure Changes After Aflibercept 8 mg and Faricimab-svoa Intravitreal Injections in Wet Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {17},
number = {7},
pages = {e88617},
pmid = {40861593},
issn = {2168-8184},
abstract = {Introduction A standard practice for addressing wet age-related macular degeneration (WetAMD) is to deliver anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. Formulations with higher concentrations, such as aflibercept 8 mg (Eylea HD; Bayer AG, Leverkusen, Germany), which are administered in larger volumes, may raise concerns about potential increases in intraocular pressure (IOP) and other ocular complications. The objective of this study was to evaluate and compare short-term IOP changes following intravitreal injection of aflibercept 8 mg (Eylea HD, 0.07 mL) versus faricimab-svoa (Vabysmo, 0.05 mL; Roche Pharma, Basel, Switzerland/Genentech, South San Francisco, CA, USA) in patients with WetAMD. Methods A retrospective observational analysis was conducted involving patients with WetAMD who received intravitreal injections of aflibercept 8 mg (n = 64 eyes) or faricimab-svoa (n = 73 eyes). IOP was measured before the injection and 30 minutes after. The research recorded lens condition, the need for paracentesis, and the application of Iopidine drops. Patients were categorized into phakic and pseudophakic subgroups, and further stratified based on post-injection IOP levels: <20 mmHg, 20-25 mmHg, 25-30 mmHg, and >30 mmHg. Results Both treatment groups showed notable increases in IOP at 30 minutes after injection (Eylea HD: +4.50 ± 4.32 mmHg, Vabysmo: +3.66 ± 5.20 mmHg; p = 0.083). However, there were no instances requiring paracentesis, and only one patient from each group needed Iopidine drops. Pseudophakic patients experienced slightly higher IOP increases (Eylea HD: +4.71 ± 4.18 mmHg, Vabysmo: +4.55 ± 5.65 mmHg; p = 0.784) compared to phakic patients. The majority of patients maintained IOP levels under 30 mmHg. Gender distribution was 49% male and 51% female. Conclusions Intravitreal injections of aflibercept 8 mg and faricimab-svoa caused a small and temporary increase in IOP and there were no cases requiring urgent management. Our results confirm the short-term ocular safety of aflibercept 8 mg and faricimab-svoa for the treatment of WetAMD and highlight the need for individualized monitoring for patients at risk of increased IOP.},
}
@article {pmid40861328,
year = {2025},
author = {Kritfuangfoo, T and Li, Y and Mieler, WF},
title = {Clinical Characteristics and Treatment Outcomes of Breakthrough Vitreous Hemorrhage in Peripheral Exudative Hemorrhagic Chorioretinopathy (PEHCR).},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {2821-2833},
pmid = {40861328},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the clinical characteristics and treatment outcomes of breakthrough vitreous hemorrhage secondary to peripheral exudative hemorrhagic chorioretinopathy (PEHCR).<br><br>METHODS: This retrospective study included 14 eyes from 14 patients with vitreous hemorrhage secondary to peripheral retinochoroidal mass lesions. Data collected included demographic profiles, clinical presentation, multimodal imaging findings, and treatment outcomes following pars plana vitrectomy (PPV), intravitreal anti-VEGF injections, or laser photocoagulation.<br><br>RESULTS: The median age at presentation was 83 years (range, 58-91), with nine females (64.3%). Median presenting visual acuity (VA) was 1.3 logMAR (range, 0.3-2.7). All patients had normal intraocular pressure. Bilateral PEHCR was observed in 50%, though hemorrhage occurred unilaterally. Unifocal lesions were present in 71.4%, with a mean lesion thickness of 3.4 mm (range, 1.5-6.8 mm). Dense vitreous hemorrhage obscuring posterior pole details was seen in eight eyes (57.1%) and required PPV. The remaining six eyes, with moderate hemorrhage, improved spontaneously without surgery. Intravitreal anti-VEGF therapy was administered in five eyes for macular involvement or to prevent recurrent hemorrhage. At a median follow-up of 11.7 months (range, 3-63), median VA improved to 0.36 logMAR (range, 0.1-2.0). The mean VA gain was 0.76 logMAR in the vitrectomy group (p = 0.004) and 0.55 logMAR in eyes without macular involvement (p = 0.024). However, five eyes (35.7%) had final VA &#x2264; 20/200 due to macular pathology consistent with age-related macular degeneration or polypoidal choroidal vasculopathy-like changes.<br><br>CONCLUSION: PEHCR with breakthrough vitreous hemorrhage is a rare but important diagnostic consideration in patients presenting with peripheral retinochoroidal mass-like lesions. PPV and intravitreal anti-VEGF therapy may improve visual outcomes in these cases. However, visual recovery may be limited in cases with macular involvement due to irreversible retinal damage. Early diagnosis and tailored management are essential to optimize outcomes and avoid misdiagnosis.},
}
@article {pmid40858363,
year = {2025},
author = {Ma, K and Ratnapriya, R},
title = {Molecular and genetic landscapes of retina and brain microglia in neurodegenerative diseases.},
journal = {Genome research},
volume = {35},
number = {10},
pages = {2143-2157},
pmid = {40858363},
issn = {1549-5469},
mesh = {*Microglia/metabolism/pathology ; Humans ; *Retina/metabolism/pathology ; *Brain/metabolism/pathology ; Genome-Wide Association Study ; *Macular Degeneration/genetics/pathology ; *Alzheimer Disease/genetics/pathology/metabolism ; *Neurodegenerative Diseases/genetics/pathology ; Transcriptome ; Epigenesis, Genetic ; },
abstract = {Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia through integrative analyses of single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq) from 97 independent human samples across 11 different studies. Our findings reveal that retina and brain microglia share similar expression and regulatory profiles compared with other cell types in the retina and brain. By integrating genome-wide association study (GWAS) data with gene expression profiles, we demonstrate that genetic variants associated with AMD and AD are linked to microglia-specific gene signatures. Furthermore, integrating regulatory annotations with GWAS data shows that susceptibility loci for both AMD and AD are notably enriched in the open chromatin regions of microglia from the brain and retina, emphasizing their relevance to these neurodegenerative conditions. Finally, a comparison with microglia annotations from other tissues highlights the specific enrichment of microglia in relation to neurodegenerative diseases. These findings contribute to the understanding of the role of microglia in AMD and AD pathogenesis and offer an opportunity to utilize resources from both retinal and brain microglia to deepen our understanding of their contributions to genetic variations in neurodegenerative diseases.},
}
@article {pmid40857064,
year = {2024},
author = {Hui, VWK and Tsang, CW and Mohamed, S and Fong, AHC and Lai, TYY and Brelen, M and Szeto, SKH},
title = {Subretinal tissue plasminogen activator without vitrectomy for submacular hemorrhage displacement using Nano-vitreoretinal gateway device: A pilot report.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001699},
pmid = {40857064},
issn = {1937-1578},
abstract = {PURPOSE: To evaluate the surgical outcome of subretinal tissue plasminogen activator (tPA) delivered without vitrectomy for the displacement of submacular hemorrhage (SMH).<br><br>METHOD: A retrospective interventional cases series of consecutive patients who underwent subretinal tPA and intravitreal expansile gas without vitrectomy for SMH displacement. Concomitant injection of subretinal air and intravitreal ranibizumab and expansile gas was performed per surgeon's discretion.<br><br>RESULTS: Seven eyes from 7 patients were included. 6 eyes (85.7%) had polypoidal choroidal vasculopathy (PCV) and 1 (14.3%) had wet age-related macular degeneration (wAMD). The median baseline visual acuity (VA) was 0.014 (range 0.005-50.1) ETDRS letters, which improved to 35 (range 26.3-65.1), 35 (range 31.0-73.9), 35 (range 35-77.3) and 35 (range 5-80.2) ETDRS letters at 1 week, 1 month, 3 months and 6 months, respectively. Visual gain of &#x2265;5 letters was achieved in majority of patients through 6 months. Successful displacement of blood away from fovea was achieved in 100% of eyes. The rate of postoperative vitreous hemorrhage, retinal pigment epithelium tear and macular hole were 14.3% (1 patient) each.<br><br>CONCLUSION: This novel, minimally invasive surgical technique is effective in displacing SMH and preserving vision.},
}
@article {pmid40855963,
year = {2025},
author = {Bommakanti, N and Momenaei, B and Wang, KY and Regillo, CD and Cohen, MN and Kuriyan, AE and Yonekawa, Y},
title = {Efficacy of Switching to Biosimilar Ranibizumab in Eyes Initially Treated with Reference Ranibizumab for Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, or Retinal Vein Occlusion.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/02713683.2025.2551165},
pmid = {40855963},
issn = {1460-2202},
abstract = {PURPOSE: To assess the efficacy of ranibizumab-eqrn for neovascular age-related macular degeneration (nAMD), macular edema from retinal vein occlusion (RVO), and diabetic macular edema (DME) in eyes switched from reference ranibizumab.<br><br>METHODS: Single-center, retrospective chart review of eyes which received at least three ranibizumab followed by at least three ranibizumab-eqrn injections over a two-year period. Eyes which were initially treated with alternative anti-VEGF agents were eligible for inclusion. Eyes that received surgery, laser, or intravitreal corticosteroids were excluded. Central foveal thickness (CFT) was measured at the initial and final visit in the ranibizumab and ranibizumab-eqrn groups for a subset of eyes. Primary outcome measures included best available visual acuity (VA) and CFT. Secondary outcome measures included number of intravitreal injections, follow-up time, and treatment interval. Analysis was performed using Python.<br><br>RESULTS: 6233 Eyes from 4935 patients treated between June 6 2022 and June 6 2024 were included. 4692 (75.3%) eyes had nAMD, 1078 (17.3%) eyes had RVO, and 463 (7.4%) eyes had DME. Eyes received 7.1&#x2009;&#xb1;&#x2009;2.7 (total: 44500) ranibizumab injections over 10.5&#x2009;&#xb1;&#x2009;2.5&#x2009;months. After switching, eyes received 5.8&#x2009;&#xb1;&#x2009;2.2 (total: 35840) ranibizumab-eqrn over 8.5&#x2009;&#xb1;&#x2009;1.7&#x2009;months. Mean change in visual acuity was -1.0&#x2009;&#xb1;&#x2009;16.0 letters for ranibizumab vs. -0.6&#x2009;&#xb1;&#x2009;13.8 letters for ranibizumab-eqrn (p&#x2009;=&#x2009;0.15). Mean change in CFT in a subset of 100 eyes was 0.81&#x2009;&#xb1;&#x2009;56.3 microns for ranibizumab vs. -7.2&#x2009;&#xb1;&#x2009;50.6 microns for ranibizumab-eqrn (p&#x2009;=&#x2009;0.39). Mean injection interval increased from 8.3&#x2009;weeks to 8.9&#x2009;weeks in the ranibizumab vs. the ranibizumab-eqrn groups for all indications (p&#x2009;<&#x2009;0.01).<br><br>CONCLUSIONS: In this large real-world study, eyes with nAMD, RVO, and DME switched to ranibizumab-eqrn from reference ranibizumab demonstrated similar efficacy.},
}
@article {pmid40855675,
year = {2025},
author = {Rodriguez-Cruz, JJ and Cutrufello, J and Lam, M and Nallaparaju, S and Peppas, NA},
title = {Drug Delivery Technologies for the Treatment of Age-Related Macular Degeneration.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {39},
pages = {e03212},
pmid = {40855675},
issn = {2198-3844},
support = {2137420//National Science Foundation/ ; },
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Drug Delivery Systems/methods ; *Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; },
abstract = {Age-related macular degeneration (AMD) is a progressive and degenerative disease affecting the posterior segment of the eye. It currently affects millions of people worldwide, and the gold standard of treatment has remained unchanged for over 20 years. It consists of intravitreal injections of anti-vascular endothelial growth factor (Anti-VEGF), which pose significant challenges to patient compliance primarily due to accessibility issues, fear of injections in the eye, and high cost. In this review, a thorough description of the pathogenesis of AMD and the anatomical barriers is presented that must be considered for the design of newer drug delivery systems for the treatment of AMD. Likewise, a critical evaluation of the most recent research efforts in the literature regarding the treatment of AMD using novel drug delivery technologies is provided. Lastly, currently approved therapeutic agents are reviewed for AMD and provide an insight into the recent surge of biosimilars with an outlook on how future therapeutic approaches to AMD should be developed.},
}
@article {pmid40854408,
year = {2025},
author = {Yu, J and Yuan, J},
title = {Association between gut microbiota dysbiosis and age-related macular degeneration progression: A bioinformatics approach.},
journal = {Experimental eye research},
volume = {260},
number = {},
pages = {110596},
doi = {10.1016/j.exer.2025.110596},
pmid = {40854408},
issn = {1096-0007},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/genetics/microbiology ; *Macular Degeneration/genetics/metabolism ; Disease Progression ; *Computational Biology/methods ; Biomarkers/metabolism ; },
abstract = {Gut microbiota dysbiosis has been linked to the progression of age-related macular degeneration, though the underlying molecular mechanisms remain unclear. This study is the first to systematically link gutMGene-derived genes to AMD pathogenesis using a multi-algorithm machine learning approach. Using the gutMGene database, we identified gut microbiota-related genes and analyzed the GSE29801 dataset for differential expression. Our enrichment analysis revealed unique insights into the involvement of gut microbiota-related genes in inflammatory, immune response, and metabolic pathways in age-related macular degeneration. Machine learning algorithms (LASSO, Random Forest, XGBoost) identified five consistent biomarker genes: CXCL10, FADS3, GHRL, APOE, and VEGFA. A nomogram was developed to predict AMD risk, showing moderate-to-high predictive accuracy with area under the curve of 0.719 (GSE29801) and 0.933 (GSE99248). Gene set variation analysis indicated upregulation of inflammatory and immune pathways and downregulation of lipid metabolism pathways in age-related macular degeneration. Single-gene set enrichment analysis further underscored the roles of diagnostic genes in immune response and metabolic regulation. This study contributes novel evidence that gut microbiota dysbiosis influences AMD progression through systemic inflammatory and metabolic pathways, and highlights potential therapeutic targets.},
}
@article {pmid40849525,
year = {2025},
author = {Du, Y and Jiang, S and Feng, L and Lu, J and Peng, H and Zhou, X},
title = {Proteomics on choroidal neovascularization based on itraq and the protective effect of TAB1 in CNV.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {31037},
pmid = {40849525},
issn = {2045-2322},
support = {81170858//National Natural Science Foundation of China/ ; 81170858//National Natural Science Foundation of China/ ; 81170858//National Natural Science Foundation of China/ ; 81170858//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Proteomics/methods ; Rats ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Male ; Interleukin-6/metabolism ; Disease Models, Animal ; Signal Transduction ; Interleukin-18/metabolism ; Rats, Sprague-Dawley ; Cell Proliferation ; NF-kappa B/metabolism ; },
abstract = {Choroidal neovascularization (CNV) is a severe pathological outcome of age-related macular degeneration (AMD) which could lead to blindness. The present study was aimed at exploring the mechanisms of CNV, hoping to provide new clues in finding the treatment target of CNV. ITRAQ approach was applied to analyze the proteins in choroidal neovascularization of CNV and normal rats. KEGG and GO annotation were used to analyze the differently-expressed proteins. Western Blotting was used as the method to identify the differently-expressed proteins. TAB1, one of the differently-expressed proteins, was chosen as the study objective in the following research. AAV-TAB1 over-expression vehicle was constructed to investigate the function of TAB1 in CNV. IL-6 and IL-18 were tested with the use of ELISA. Western Blotting was used to test the expression of NF-kB pathway molecules. In terms of the results, expressions of 49 kinds of proteins were up-regulated in CNV rats while expressions of 241 kinds of proteins were down-regulated among the 4380 identified proteins. Overexpression of TAB1 significantly reduced areas of CNV lesions in vivo. Cell proliferation significantly increased in the TAB1 over-expressed group in RPE. IL-6 expression significantly increased in the TAB1-overexpression group while IL-18 expression significantly reduced. Western blotting results showed NF-kB pathway molecules were involved in it. The present study suggests TAB1 may play a protective role in CNV progression and the relative pathway owns the potential to be the treating target of CNV.},
}
@article {pmid40845040,
year = {2025},
author = {Sumi, S and Asaoka, R and Aoki, S and Kitamoto, K and Terao, R and Kawata, M and Inoue, T and Obata, R and Azuma, K},
title = {Corneal biomechanical predictors of intraocular pressure elevation after intravitreal anti-VEGF injection.},
journal = {PloS one},
volume = {20},
number = {8},
pages = {e0330574},
pmid = {40845040},
issn = {1932-6203},
mesh = {Humans ; *Intraocular Pressure/drug effects ; Male ; Female ; Aged ; Intravitreal Injections/adverse effects ; *Cornea/physiopathology/drug effects ; Retrospective Studies ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Biomechanical Phenomena ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Middle Aged ; Macular Degeneration/drug therapy/physiopathology ; Retinal Vein Occlusion/drug therapy/physiopathology ; },
abstract = {PURPOSE: To investigate whether corneal biomechanical parameters measured via Corvis ST can predict acute intraocular pressure (IOP) elevation following intravitreal anti-VEGF injection.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Forty eyes from patients with neovascular age-related macular degeneration or retinal vein occlusion who underwent anti-VEGF therapy.<br><br>METHODS: IOP was measured using the Corvis ST immediately before and 10 minutes after injection. The following biomechanical parameters were evaluated: DA Ratio MAX (2mm), biomechanically corrected IOP (bIOP), Peak Distance, Deflection Amplitude Max, Integrated Radius, and Stress-Strain Index (SSI).<br><br>MAIN OUTCOME MEASURES: Acute post-injection IOP elevation (continuous) and IOP spikes &#x2265;10 mmHg (binary).<br><br>RESULTS: The mean IOP increased significantly from 14.5&#x2009;&#xb1;&#x2009;3.17 to 24.7&#x2009;&#xb1;&#x2009;7.44 mmHg post-injection (p < 0.0001). IOP spikes &#x2265;10 mmHg occurred in 55% of eyes. On multivariate analysis, higher bIOP (&#x3b2; = +1.17, p = 0.048) and lower DA Ratio MAX (&#x3b2; = -5.40, p = 0.038) were independent predictors of IOP elevation. DA Ratio MAX was the only significant predictor of IOP spikes (OR = 0.70, 95% CI: 0.51-0.96, p = 0.035). ROC analysis showed that DA Ratio MAX alone (AUC = 0.739) outperformed bIOP (AUC = 0.607), with the combined model yielding the highest AUC (0.773). A cutoff of DA Ratio MAX &#x2264;4.936 provided 81.8% sensitivity and 42.9% specificity for predicting spikes.<br><br>CONCLUSIONS: DA Ratio MAX (2mm), reflecting global ocular compliance, was a significant predictor of acute IOP spikes after anti-VEGF injection. Alongside bIOP, it may be useful for pre-injection risk stratification of pressure-related complications.},
}
@article {pmid40843791,
year = {2025},
author = {Amaral, DC and Magalhães, PLM and Alfatih, M and Miranda, BG and Abu Serhan, H and Jacometti, R and Ferreira, BFA and Sant'Ana, L and Santos, DH and Monteiro, MLR and Louzada, RN},
title = {CPAP Use and Retinal Disease Risk in Obstructive Apnea: A Cohort Study.},
journal = {Vision (Basel, Switzerland)},
volume = {9},
number = {3},
pages = {},
pmid = {40843791},
issn = {2411-5150},
abstract = {Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) therapy reduces retinal disease incidence among adults with OSA and BMI between 25.0 and 30.0 kg/m[2]. After 1:1 propensity score matching, 101,754 patients were included in the analysis. Retinal outcomes included diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), and central serous chorioretinopathy (CSC). CPAP use was associated with a modest but statistically significant reduction in DR (3.2% vs. 3.4%, RR: 0.922, p = 0.016) and AMD (2.1% vs. 2.3%, RR: 0.906, p = 0.018), while no significant differences were found for RVO or CSC. These findings support prior evidence linking CPAP to improved retinal microvascular health and suggest a protective effect against specific retinal complications. Limitations include a lack of data on CPAP adherence, OSA severity, and imaging confirmation. Still, this study highlights the importance of interdisciplinary care between sleep and eye health, and the need for further prospective studies to validate CPAP's role in preventing retinal disease progression in OSA patients.},
}
@article {pmid40841412,
year = {2025},
author = {Saito, M and Imaizumi, K},
title = {Two-year results of switching to intravitreal administration of faricimab in patients with aflibercept-refractory neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30699},
pmid = {40841412},
issn = {2045-2322},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Female ; Male ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Aged ; Intravitreal Injections ; Visual Acuity/drug effects ; Retrospective Studies ; Aged, 80 and over ; *Macular Degeneration/drug therapy/pathology ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Middle Aged ; Follow-Up Studies ; Drug Substitution ; Tomography, Optical Coherence ; Antibodies, Bispecific ; },
abstract = {We evaluated the efficacy of switching to intravitreal injection of faricimab (IVF) in patients with aflibercept-refractory neovascular age-related macular degeneration (nAMD) over 2 years of follow-up. We retrospectively reviewed 47 consecutive eyes of 45 Japanese patients with nAMD who switched from aflibercept to faricimab. Thirty-one eyes of 30 Japanese patients were included in this study. The mean visual acuity (BCVA) at month 24 was stable relative to the baseline. The mean central retinal thickness and subfoveal choroidal thinning significantly decreased at 24 months (P < 0.0001, P < 0.0001, respectively). At 24 months, 22 eyes (70.0%) achieved a dry macula and had improved VA levels with an improvement of 0.80 lines, which was significantly different from the remaining 9 eyes (P < 0.01). The mean interval of IVF was 11.8 weeks, which was significantly longer than that of aflibercept (10.0 weeks) at baseline (p = 0.014). Progression of macular atrophy or newly developing macular atrophy was seen in 3 eyes (9.7%), showing decline of 1.0 line, no other complications were seen. These results indicate that switching to IVF stabilized VA, significantly improved the anatomical changes and the achievement of a dry macula was significantly associated with the visual outcome, in patients with aflibercept-refractory nAMD over a 24-month period.},
}
@article {pmid40854166,
year = {2025},
author = {Quarta, A and He, Y and Corradetti, G and Alhelaly, M and Soylu, C and Abbasgholizadeh, R and Popovic, M and Chujo, S and Chung, YC and Kwak, HD and Velaga, SB and Nittala, MG and Sadda, SR},
title = {Intraretinal Sclero-Choroidal Vessels in Eyes with Severe Chorioretinal Thinning: Hypothesis on Bruch's Membrane Failure.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001797},
pmid = {40854166},
issn = {1937-1578},
abstract = {PURPOSE: To describe the multimodal imaging features of intraretinal sclero-choroidal vessels (ISCVs) in eyes with severe chorioretinal thinning.<br><br>METHODS: A retrospective observational case series. We examined 6 eyes of 6 patients with advanced chorioretinal thinning presenting to the Doheny UCLA Eye Centers (pathologic myopia with posterior staphyloma, iatrogenic staphyloma, chronic anti-VEGF exposure, or non-myopic macular atrophy). All patients underwent structural optical coherence tomography (OCT), and when available, eyes were additionally imaged with OCT angiography (OCTA). Clinical records, fundus photography, and OCT scans were reviewed to assess vessel morphology, anatomical location and course, relationship to BM, and associated chorioretinal changes.<br><br>RESULTS: In all six cases, a large-caliber, non-exudative sclero-choroidal vessel was observed entering into the neurosensory retina. OCT consistently showed a hyperreflective tubular wall with a hyporeflective lumen, often occupying more than 50% of the retinal thickness at the point of entry. All vessels emerged at sites of focal BM disruption, typically within zones of marked choroidal thinning, posterior staphyloma, or atrophic remodeling. OCTA when available confirmed intraluminal flow, with no evidence of surrogate biomarkers of leakage or neovascular proliferation. Accurate identification required careful multimodal assessment to distinguish these ISCVs from mimicking conditions.<br><br>CONCLUSIONS: ISCVs represent a novel structural finding characterized by passive migration of a sclero-choroidal vessel into the retina through areas of BM disruption. ISCVs are non-proliferative and clinically stable, and should be distinguished from more typical exudative lesions on structural OCT. Recognition of ISCVs avoids misdiagnosis and unnecessary treatment.},
}
@article {pmid40853572,
year = {2025},
author = {Lacanilao, JPB and Artiaga, JCM},
title = {Polypoidal choroidal vasculopathy features among Filipino eyes with neovascular AMD: application of the Asia Pacific Ocular Smaging Society non-ICGA criteria.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {351},
pmid = {40853572},
issn = {1573-2630},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Retrospective Studies ; Cross-Sectional Studies ; Aged ; Male ; Middle Aged ; Aged, 80 and over ; *Fluorescein Angiography/methods ; Philippines/epidemiology ; *Choroid/blood supply ; *Wet Macular Degeneration/diagnosis/epidemiology/complications ; Fundus Oculi ; *Polyps/diagnosis/epidemiology ; Visual Acuity ; *Choroidal Neovascularization/diagnosis ; Societies, Medical ; Polypoidal Choroidal Vasculopathy ; },
abstract = {BACKGROUND/OBJECTIVES: To determine the proportion of eyes with optical coherence tomography (OCT) features of polypoidal choroidal vasculopathy (PCV) among patients diagnosed as neovascular age-related macular degeneration (nAMD) based on Asia-Pacific Ocular Imaging Society (APOIS) Diagnostic Criteria.<br><br>METHODS: This study was a retrospective cross-sectional review of OCT images. Medical records of treatment-na&#xef;ve nAMD patients between January 2018 and June 2023 were reviewed. Clinical and demographic profile at presentation was collected. OCT scans were reviewed for presence of APOIS Diagnostic Criteria. Eyes were classified as having PCV features (PCV) based on the presence of &#x2265;&#x2009;2 major OCT APOIS diagnostic criteria and then compared with eyes not having these features (non-PCV).<br><br>RESULTS: OCT scans of 45 eyes of 38 patients diagnosed with nAMD were analyzed. Mean age was 69.4 years old (range 53-83), 71.1% of patients were female, and 81.6% had unilateral disease. There was no statistically significant difference among clinical and demographic characteristics between PCV and non-PCV groups. Twenty-four eyes (53.3%) had &#x2265;&#x2009;2 major APOIS criteria for PCV. Among PCV eyes, sub-RPE ring-like lesion and double-layer sign were the most common major (87.5%) and minor OCT criteria (100%), respectively. Sharp-peaked PED (p&#x2009;<&#x2009;0.001), sub-RPE ring-like lesion (p&#x2009;<&#x2009;0.001), en face OCT complex RPE elevation (p&#x2009;=&#x2009;0.005) and double-layer sign criteria (p&#x2009;=&#x2009;0.007) were more frequent in the PCV than in the non-PCV group.<br><br>CONCLUSION: More than half of Filipino eyes diagnosed with nAMD fulfill the OCT criteria for PCV. The APOIS PCV Workgroup Criteria helps identify patients who will benefit from additional confirmatory and treatment options.},
}
@article {pmid40852622,
year = {2025},
author = {Bikbov, MM and Kazakbaeva, GM and Panda-Jonas, S and Valishin, ID and Nizamutdinova, AM and Jonas, JB},
title = {Intravitreal panitumumab and retinal pigment epithelium proliferation in laser-induced retinal degeneration in rabbits.},
journal = {Frontiers in ophthalmology},
volume = {5},
number = {},
pages = {1641194},
pmid = {40852622},
issn = {2674-0826},
abstract = {PURPOSE: This study aims to examine the effect of intravitreally applied epidermal growth factor (EGF) receptor blocker panitumumab on the proliferation of retinal pigment epithelium cells (RPE) in an experimental model of localized retinal degeneration.<br><br>METHODS: The experimental study included rabbits with age of 2 to 3 months and body weight of 2.5-3 kg and which were randomly distributed into a study group and control group. The right eyes received two retinal argon laser coagulation spots (500 mW; diameter, 100 &#x3bc;m; duration, 0.5 s), applied with an interval of 2 min at the same location close to the vascular streak in the posterior fundus region. For five times at 2-day intervals, the rabbits of the study group received intravitreal injections of 1 mg panitumumab (0.10 mL), and the rabbits of the control group had intravitreal injections of 0.10 mL Ringer's solution. At baseline, at each time point of re-examination, and at study end, the animals were examined by fundus photography and optical coherence tomography of the laser spot.<br><br>RESULTS: The study included 19 rabbits (study group: 10 animals; control group: nine animals). After the third injection and at study end, the laser-induced area of depigmentation + hyperpigmentation combined did not vary significantly between the study group and the control group (1.43 &#xb1; 0.63 mm[2] versus 1.63 &#xb1; 0.77 mm[2]; P = 0.56; and 1.37 &#xb1; 0.63 mm[2] versus 1.61 &#xb1; 0.74 mm[2]; P = 0.46, respectively). At the same time points, the area with hyperpigmentation was significantly smaller in the study group than in the control group (0.16 &#xb1; 0.15 mm[2] versus 0.80 &#xb1; 0.59 mm[2]; P = 0.01; and 0.14 &#xb1; 0.14 mm[2] versus 0.70 &#xb1; 0.56 mm[2]; P = 0.02, respectively). At the same time points, the ratio of the hyperpigmented area to the combined depigmented + hyperpigmented area was significantly smaller in the study group than in the control group (0.11 &#xb1; 0.09 versus 0.43 &#xb1; 0.19 mm[2]; P < 0.001; and 0.10 &#xb1; 0.08 versus 0.35 &#xb1; 0.23mm[2]; P = 0.006, respectively).<br><br>CONCLUSIONS: These findings indicate that intravitreally administered panitumumab was associated with reduced subretinal hyperpigmentation in a laser-induced model of retinal injury. While this may reflect a modulation of the RPE response, including the potential suppression of RPE proliferation, further studies incorporating histological and molecular analyses are warranted to confirm its effect on subretinal fibrosis.},
}
@article {pmid40852330,
year = {2025},
author = {Dhoot, DS and Shah, CP and Silva, FQ and McCullough, AJ and Du, W and Moini, H and Kaiser, PK},
title = {Impact of Central Subfield Thickness Fluctuations on Visual Outcomes in Neovascular Age-Related Macular Degeneration in the VIEW Trials.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251359902},
pmid = {40852330},
issn = {2474-1272},
abstract = {Purpose: To evaluate the impact of central subfield thickness (CST) fluctuations on visual outcomes in treatment-naïve eyes with neovascular age-related macular degeneration from VIEW 1 and VIEW 2. Methods: Eyes were treated with intravitreal ranibizumab 0.5 mg every 4 weeks (Rq4) or aflibercept 2 mg every 4 or 8 weeks (2q4 or 2q8). The relationship between CST fluctuations and visual outcomes was evaluated via mixed model for repeated measures in quartiles of SDs of CST from baseline to week 52 (n = 1792; quartile 1: ≤27.6 µm; quartile 2: >27.6 to ≤42.5 µm; quartile 3: >42.5 to ≤65.3 µm; quartile 4: >65.3 µm) and weeks 12 to 52 (n = 1766; quartile 1: ≤27.0 µm; quartile 2: >27.0 to ≤43.2 µm; quartile 3: >43.2 to ≤67.8 µm; quartile 4: >67.8 µm). Results: Least squares mean best-corrected visual acuity (BCVA) gains from baseline to week 52 for quartile 1 to quartile 4 were 9.6, 10.1, 9.6, and 6.7 letters, respectively (quartile 4 vs quartile 1: nominal P = .0017). Least squares mean BCVA letter gains within each quartile treated with Rq4, 2q4, and 2q8, respectively, were 7.0, 10.3, and 10.2 (quartile 1); 11.3, 9.3, and 8.8 (quartile 2); 10.0, 9.3, and 10.1 (quartile 3); and 7.4, 8.4, and 6.2 (quartile 4). From weeks 12 to 52, least squares mean BCVA gains for quartile 1 to quartile 4 were 10.0, 9.7, 9.7, and 6.9 letters, respectively (quartile 4 vs quartile 1: nominal P = .0008). Least squares mean BCVA letter gains within each quartile treated with Rq4, 2q4, and 2q8, respectively, were 7.9, 10.7, and 10.6 (quartile 1); 10.7, 9.3, and 8.1 (quartile 2); 9.3, 9.5, and 10.9 (quartile 3); and 8.2, 8.0, and 6.4 (quartile 4). Conclusions: The highest CST fluctuation was associated with lower BCVA gains, irrespective of antivascular endothelial growth factor agent or regimen.},
}
@article {pmid40850524,
year = {2025},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Is acupuncture a viable therapeutic strategy for degenerative eye diseases? a systematic review and meta-analysis.},
journal = {Complementary therapies in medicine},
volume = {93},
number = {},
pages = {103235},
doi = {10.1016/j.ctim.2025.103235},
pmid = {40850524},
issn = {1873-6963},
mesh = {Humans ; *Acupuncture Therapy/methods ; *Eye Diseases/therapy ; Visual Acuity ; Intraocular Pressure ; },
abstract = {INTRODUCTION: Degenerative ocular diseases-glaucoma, age-related macular degeneration (AMD), optic atrophy, and retinitis pigmentosa (RP)-are major causes of irreversible vision loss. Acupuncture, a traditional Chinese therapy, has shown promise in improving visual function through neuroprotective and vascular mechanisms.<br><br>METHODOLOGY: A systematic review and meta-analysis were conducted using data from PubMed, Embase, Scopus, Web of Science, Google Scholar, and Cochrane Library. Randomized controlled trials (RCTs), cohort studies, and other observational studies examined acupuncture or electroacupuncture for degenerative ocular diseases. Quality was assessed using RoB 2.0 for RCTs and ROBINS-I for non-randomized studies. Meta-analyses and narrative syntheses were performed using RevMan and rbiostistics.<br><br>RESULTS: A total of 3362 records were identified, with 21 studies meeting inclusion criteria. Acupuncture shows improvements in visual acuity, ocular blood flow, and intraocular pressure (IOP) across conditions. Meta-analyses showed a significant improvement in total effective rate favoring acupuncture (OR = 3.52; 95&#x202f;% CI: 2.18-5.68; p&#x202f;<&#x202f;0.00001), with consistent benefits across RP, AMD, and optic atrophy. However, pooled data revealed no statistically significant improvement in visual acuity (MD = -0.03; p&#x202f;=&#x202f;0.50) or IOP (MD = -0.86&#x202f;mmHg; p&#x202f;=&#x202f;0.11). Randomized controlled trials comparing acupuncture to sham controls also showed non-significant trends. Despite some promising physiological and functional outcomes, results remain mixed, emphasizing the need for larger, well-designed studies.<br><br>CONCLUSION: Acupuncture shows potential benefits in treating degenerative eye diseases, especially in improving clinical response rates. However, its effects on visual acuity and IOP remain inconclusive, warranting further rigorous research.},
}
@article {pmid40849608,
year = {2025},
author = {Vedula, SS and Li, T},
title = {Cochrane corner: artificial intelligence for diagnosing exudative age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {15},
pages = {2736-2737},
pmid = {40849608},
issn = {1476-5454},
support = {1R01EY033065//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; UG1EY020522//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; },
}
@article {pmid40849032,
year = {2025},
author = {Zhang, C and Aboukasm, G and Lai, DA and Leung, N and Zhu, D and Albini, TA and Yannuzzi, NA},
title = {Clinical Efficacy of Switching to Faricimab in Treatment Resistant Neovascular Age-Related Macular Degeneration: Systematic Review and Meta-analysis.},
journal = {American journal of ophthalmology},
volume = {280},
number = {},
pages = {248-266},
doi = {10.1016/j.ajo.2025.08.034},
pmid = {40849032},
issn = {1879-1891},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Drug Substitution ; Treatment Outcome ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Tomography, Optical Coherence ; Antibodies, Bispecific ; },
abstract = {TOPIC: Faricimab in the treatment of treatment-resistant neovascular age-related macular degeneration (nAMD).<br><br>CLINICAL RELEVANCE: While many studies on faricimab in treatment-resistant eyes have reported improvements in retinal thickness (RT), the impact on visual acuity (VA) remains inconsistent. Additionally, variability in dosing protocols-with some studies utilizing loading interval for the first 3 injections while others continuing at the prior injection interval-introduces further uncertainty regarding the optimal treatment strategy. Understanding these differences is essential for guiding clinical decision-making and maximizing patient outcomes.<br><br>METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420251000088). A systematic search of PubMed, Embase, and Scopus (February 3, 2025) identified studies evaluating the effects of switching to faricimab in treatment-resistant nAMD. Inclusion criteria required patients to have received &#x2265;3 prior anti-VEGF injections and &#x2265;3 faricimab injections, with reported outcomes on RT, VA, fluid status, or injection intervals. Outcomes were measured following completion of loading dose and at last follow up, ranging from 3 months to 1.5 years. Studies were assessed for bias using ROBINS-I and NIH Quality Assessment tool and assessed for certainty of evidence using GRADE. Meta-analyses were conducted using mean differences, odds ratio, and random-effects models.<br><br>RESULTS: Fourteen studies (926 eyes) met inclusion criteria. Switching to faricimab significantly reduced RT by 46.67 &#xb5;m (95% CI: 35.91-57.42, I[2] = 0%, 721 eyes). Eyes that followed a loading interval were found to have greater reduction in RT than those that did not (I[2] = 74.1%, 640 eyes). The odds of achieving a dry macula increased 4.35-fold (95% CI: 2.95-6.42, I[2] = 64%, 379 eyes). Eyes with baseline VA <65 ETDRS letters showed a gain of 3.16 letters (95% CI: 0.80-5.52, I[2] = 0%, 439 eyes). Injection intervals were extended by 1.56 weeks (95% CI: 0.71-2.40, I[2] = 86%, 591 eyes). Using GRADE, 4 outcomes were graded as either very low (VA, dryness, and treatment interval) or low (RT).<br><br>CONCLUSION: Switching to faricimab in treatment-resistant nAMD eyes significantly improved RT with no change in VA. This effect was greater with a loading interval protocol. Overall, there was an extension of injection intervals. Further prospective studies are needed to optimize dosing strategies and assess long-term efficacy.},
}
@article {pmid40849031,
year = {2025},
author = {Johnston, W and Kim, SS and Kar, D and Gao, L and Clark, ME and McGwin, G and Sloan, KR and Owsley, C and Curcio, CA and Goerdt, L},
title = {Hypertransmission and Vision in Aging and Age-Related Macular Degeneration: Longitudinal Data From ALSTAR2.},
journal = {American journal of ophthalmology},
volume = {280},
number = {},
pages = {399-413},
doi = {10.1016/j.ajo.2025.08.038},
pmid = {40849031},
issn = {1879-1891},
mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; *Aging/physiology ; Fluorescein Angiography/methods ; Follow-Up Studies ; *Macular Degeneration/physiopathology/diagnosis ; *Night Vision/physiology ; Middle Aged ; *Color Vision/physiology ; Aged, 80 and over ; Mesopic Vision/physiology ; Dark Adaptation/physiology ; },
abstract = {PURPOSE: To investigate the presence of hypertransmission (HT) in normal aging, early (e)AMD, and intermediate (i)AMD, changes over 3 years, and the impact of HTs ≥ 250 µm (LHyperTD) on 7 tests of scotopic, mesopic, and photopic vision.<br><br>DESIGN: Prospective cohort study.<br><br>SUBJECTS: Participants of the Alabama Study on Early Age-Related Macular Degeneration 2.<br><br>METHODS: ALSTAR2 participants underwent spectral domain optical coherence tomography angiography (OCTA), color fundus photography, and vision testing at baseline and 3-year follow-up. HT presence and stepped diameters in choroidal en face slabs were assessed with custom review software. Only LHyperTD were analyzed at follow-up. AMD was staged via AREDS 9-step. Vision at baseline and follow-up between eyes with and without LHyperTD was analyzed with linear regression.<br><br>MAIN OUTCOME MEASURES: Presence, size, and illustrative examples of HT, association with tests of photopic, mesopic and scotopic vision.<br><br>RESULTS: Baseline data was available on 460 eyes of 460 patients (mean age 71.5 &#xb1; 5.7 years, 277 female; 236 normal, 134 eAMD, 90 iAMD). HT of any size were found in iAMD (86.7%), eAMD (35.1%), and normal (3.8%) eyes, with proportional LHyperTD (13.3% vs 4.2% vs 0.4%, P < .01). For 339 eyes (mean age 71.2 &#xb1; 5.8 years, 206 female, 181 normal, 92 eAMD, 66 iAMD), LHyperTD presence significantly increased in normal (P = .01) and iAMD (P < .01) but not in eAMD eyes. At baseline, photopic contrast sensitivity (CS), mesopic CS, and rod intercept time (for rod mediated dark adaptation, RMDA) were worse in eyes with LHyperTD compared to eyes without (all P < .01). At follow-up, the same were worse in LHyperTD (all P < .01), as well as low luminance visual acuity (P < .01) and scotopic light sensitivity (P = .05).<br><br>CONCLUSION: LHyperTD are rare in normal and eAMD eyes and associate with mesopic and scotopic visual functions in addition to risk-indicating RMDA. Delayed RMDA reflects other factors other than LHyperTD including differences in disease stage. Our analysis of HT < 250 &#xb5;m may inform other studies of early disease. LHyperTD are best utilized as imaging biomarkers for later stages of iAMD than ALSTAR2.},
}
@article {pmid40848399,
year = {2025},
author = {Jiang, Y and Wang, H and Jiang, L and Chen, J and Li, T and Zhang, G and Chen, X and Jiang, M and Sun, X},
title = {Generation of the induced pluripotent stem cell line SJTUGHi004-A derived from a Best's disease patient with c.763C &gt; T mutation in BEST1 gene.},
journal = {Stem cell research},
volume = {88},
number = {},
pages = {103806},
doi = {10.1016/j.scr.2025.103806},
pmid = {40848399},
issn = {1876-7753},
mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/pathology ; *Bestrophins/genetics ; *Vitelliform Macular Dystrophy/genetics/pathology/metabolism ; Cell Line ; *Mutation ; Cell Differentiation ; Male ; Leukocytes, Mononuclear/metabolism ; },
abstract = {Best's disease (BD), referred to as Best vitelliform macular dystrophy, is an autosomal dominant macular degeneration caused by mutations in the BESTROPHIN1 (BEST1) gene. Here, we generated an induced pluripotent stem cell (iPSC) line by the non-integrative Sendai-virus delivery system derived from peripheral blood mononuclear cells (PBMCs) of a patient with c.763C > T mutation in the BEST1 gene. The iPSC line was characterized and validated for the karyotype stability, pluripotency markers, and differentiation potential in vitro, which may serve as a powerful model for exploring the pathological mechanism and pharmaceutical development.},
}
@article {pmid40846247,
year = {2025},
author = {Yang, X and Ma, A and Liu, Y and He, Z and Yu, J and Su, S and Chen, J and Sang, A},
title = {Lysyl oxidase-like 2 inhibition alleviates subretinal fibrosis in neovascular age-related macular degeneration model.},
journal = {Experimental eye research},
volume = {260},
number = {},
pages = {110588},
doi = {10.1016/j.exer.2025.110588},
pmid = {40846247},
issn = {1096-0007},
mesh = {Animals ; *Amino Acid Oxidoreductases/antagonists &amp; inhibitors/genetics ; Fibrosis/prevention &amp; control ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Oxidative Stress ; Epithelial-Mesenchymal Transition ; Cellular Senescence ; Cells, Cultured ; *Wet Macular Degeneration/pathology/metabolism/drug therapy ; Male ; Humans ; },
abstract = {Subretinal fibrosis is a significant contributing factor to the irreversible vision loss linked with neovascular age-related macular degeneration (nAMD). Cellular senescence, a process implicated in the development of nAMD, has been suggested to promote fibrosis through epithelial-mesenchymal transition (EMT). LOXL2 (Lysyl oxidase-like 2) is associated with a variety of fibrotic conditions. However, the role of LOXL2 in subretinal fibrosis remains to be elucidated. In the study, we induced retinal pigment epithelium (RPE) senescence in vitro and in vivo. Further analysis showed that conditioned medium from senescent RPE upregulated the expression of mesenchymal and fibrogenic markers in pre-senescent RPE. LOXL2 silencing was found to attenuate RPE senescence and suppress conditioned medium induced EMT, which was associated with reduced oxidative stress and linked to the TGF-β1/p38 MAPK pathway. In vivo studies confirmed these findings, showing that systemic LOXL2 inhibition reduced D-galactose (D-gal) induced senescence and subretinal fibrosis following laser injury in mice. This treatment also partially corrected the redox imbalance and abnormal activation of TGF-β1/p38 MAPK pathway. The findings indicate that LOXL2 inhibition may be a promising therapeutic approach to prevent subretinal fibrosis in nAMD, providing a novel intervention strategy for a condition for which there are currently no effective treatments.},
}
@article {pmid40844677,
year = {2025},
author = {Maehara, Y and Notomi, S and Shiose, S and Fukuda, Y and Kiyohara, K and Kano, K and Ishikawa, K and Hisatomi, T and Sonoda, KH},
title = {Switching to faricimab alleviates persistent subretinal fluid and pigment epithelial detachment in neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {40844677},
issn = {1613-2246},
support = {JP21K09702//Japan Society for the Promotion of Science/ ; },
abstract = {PURPOSE: To evaluate structural outcomes, including subretinal fluid (SRF) and fibrovascular pigment epithelial detachment (fvPED) volume changes, after switching from aflibercept 2 mg to faricimab in Japanese patients with neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective, observational study.<br><br>METHODS: Patients with nAMD who were switched from aflibercept 2 mg to faricimab were enrolled. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and the volumes of SRF and fvPED were analyzed using three-dimensional spectral-domain optical coherence tomography data.<br><br>RESULTS: A total of 46 eyes from 46 patients were included. All had been maintained on fixed dosing due to difficulty in extending the injection interval. Patients had received a mean of 25.6 aflibercept 2&#xa0;mg injections, with a mean interval of 7.5&#xa0;weeks for the last three injections. Subsequently, three faricimab injections were given at similar intervals (7.6&#xa0;weeks). BCVA remained unchanged (p = 0.066), while CMT, SRF, and fvPED volumes significantly decreased (p < 0.01). A significant correlation was found between the reductions in SRF and fvPED volumes (p < 0.05).<br><br>CONCLUSIONS: Switching to faricimab led to favorable structural outcomes in nAMD patients previously treated with aflibercept 2&#xa0;mg, particularly by reducing SRF and fvPED.},
}
@article {pmid40843649,
year = {2025},
author = {Stráňava, J and Ugarova, D and Stepanov, A},
title = {Subhyaloid Hemorrhage after Bungee Jumping Experience. A Case Report.},
journal = {Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti},
volume = {81},
number = {Ahead of Print},
pages = {1-4},
doi = {10.31348/2025/31},
pmid = {40843649},
issn = {1211-9059},
mesh = {Humans ; Adult ; Male ; *Retinal Hemorrhage/etiology/surgery ; },
abstract = {Subhyaloid hemorrhage is defined as bleeding between the internal limiting membrane (ILM) and the posterior hyaloid membrane. The condition typically manifests itself in acute visual impairment. Causes include the Valsalva maneuver, Terson's syndrome, age-related macular degeneration (ARMD), trauma, hypercoagulable and hyperviscosity states, uncontrolled blood pressure, diabetes mellitus and leukemia. Prolonged presence of blood in the macular region can lead to the development of an epiretinal membrane and toxic damage to the retinal pigment epithelium and photoreceptors due to iron ions. In this case report we present a 32-year-old patient who was treated at the ophthalmology outpatient clinic of the Regional Hospital in Mladá Boleslav for subhyaloid hemorrhage in the right eye following a bungee jumping experience. The patient was successfully treated with Nd -YAG hyaloidotomy, which resulted in a good therapeutic outcome and full restoration of visual acuity.},
}
@article {pmid40840458,
year = {2025},
author = {Mackenbrock, LHB and Xu, ATL and Łabuz, G and Augustin, VA and Yildirim, TM and Auffarth, GU and Khoramnia, R},
title = {Quantitative Analysis of Choroidal Vascular Remodeling after Cataract Surgery: Correlation with Preoperative Lens Opacity Grading.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {8},
pages = {828-835},
doi = {10.1055/a-2644-4687},
pmid = {40840458},
issn = {1439-3999},
mesh = {Humans ; Male ; *Choroid/blood supply/diagnostic imaging ; Female ; Aged ; Tomography, Optical Coherence/methods ; *Vascular Remodeling/physiology ; *Cataract/diagnostic imaging ; Prospective Studies ; Middle Aged ; *Cataract Extraction ; Reproducibility of Results ; Aged, 80 and over ; Treatment Outcome ; *Phacoemulsification ; Sensitivity and Specificity ; },
abstract = {BACKGROUND: Cataract surgery has been shown to induce choroidal remodeling, but the underlying mechanisms remain poorly understood. This study investigates the relationship between preoperative lens opacity and postoperative changes in choroidal vascularity following phacoemulsification.<br><br>METHODS: This prospective study included 46 eyes from 46 patients undergoing routine cataract surgery. Choroidal vascularity was assessed using optical coherence tomography angiography (OCTA) before surgery and at 1, 4, and 12 weeks postoperatively. The choroidal vascularity index (CVI) was calculated using a custom computer script. Preoperative lens opacity was quantified using anterior segment optical coherence tomography (AS-OCT). Correlations between CVI changes and various surgical and anatomical parameters were analyzed.<br><br>RESULTS: The CVI decreased significantly, from 0.584&#x2009;&#xb1;&#x2009;0.036 preoperatively to 0.569&#x2009;&#xb1;&#x2009;0.037 at 12 weeks postoperatively (p&#x2009;=&#x2009;0.003). There was a significant negative correlation between the change in CVI and preoperative lens density (r&#x2009;=&#x2009;-&#x2009;0.333, p&#x2009;=&#x2009;0.036), as well as nuclear density (r&#x2009;=&#x2009;-&#x2009;0.328, p&#x2009;=&#x2009;0.039). No significant correlations were found between CVI change and cumulative dissipated energy, phacoemulsification time, fluid usage, or intraocular pressure change.<br><br>CONCLUSION: Cataract surgery induces a significant decrease in choroidal vascularity that persists for at least three months postoperatively. This decrease correlates with preoperative cataract density, suggesting that increased light transmission following lens replacement may lead to choroidal remodeling. Consequently, objective measurement of lens opacity may contribute to the decision-making process for timing cataract surgery; however, further studies are needed to evaluate its potential role in minimising short- and long-term complications, such as macular oedema or age-related macular degeneration.},
}
@article {pmid40839325,
year = {2025},
author = {Dohl, J and Burns, G and Singh, M},
title = {The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration.},
journal = {Apoptosis : an international journal on programmed cell death},
volume = {30},
number = {11-12},
pages = {2526-2546},
pmid = {40839325},
issn = {1573-675X},
support = {DGE-1839285//National Science Foundation/ ; RO1 EY027363/EY/NEI NIH HHS/United States ; RO1 EY027363/EY/NEI NIH HHS/United States ; RO1 EY027363/EY/NEI NIH HHS/United States ; },
mesh = {*Ferroptosis/genetics ; Humans ; *Mitochondria/metabolism/pathology ; *Lipid Metabolism ; *Macular Degeneration/metabolism/pathology ; Animals ; *Geographic Atrophy/metabolism/pathology/genetics ; },
abstract = {Age-related macular degeneration (AMD) is currently the leading cause of vision loss in developed countries. Despite decades of research and development, there are currently no treatments for the dry version of the illness. Dry AMD (DAMD) is a multifactorial disease stemming from dysfunction in the complement system, mitochondrial function, and lipid metabolism. While the complement system has been studied in-depth for its involvement in DAMD, mitochondria and lipids are understudied for their potential contributions to this process. Ferroptosis, an iron-dependent cell death mechanism, is associated with mitochondrial dysfunction and lipid dysregulation, and has been implicated as a driver of DAMD. This review describes the pathology of DAMD and the potential role of mitochondria, metabolism, and lipid dysregulation in the disease. We will highlight the intersection of pathways involving mitochondria, lipid dysregulation, and ferroptosis in DAMD progression, as well as the need for future studies to elucidate this connection.},
}
@article {pmid40839112,
year = {2025},
author = {Fried, S and Vorobichik Berar, O and David, D and Arazi, M and Klain, B and Cohen, GY and Fogel Levin, M and Platner, E and Katz, G and Hostovsky, A},
title = {Poor long-term fellow-eye outcomes after vitrectomy with subretinal tissue plasminogen activator for AMD-related submacular hemorrhage.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {11},
pages = {3113-3119},
pmid = {40839112},
issn = {1435-702X},
mesh = {Humans ; Male ; *Vitrectomy/methods ; Retrospective Studies ; Female ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Visual Acuity ; Aged, 80 and over ; *Retinal Hemorrhage/etiology/diagnosis/therapy/surgery ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Fibrinolytic Agents/administration &amp; dosage ; Aged ; Time Factors ; Treatment Outcome ; Intravitreal Injections ; Fluorescein Angiography ; Prognosis ; *Wet Macular Degeneration/complications/diagnosis ; Fundus Oculi ; },
abstract = {PURPOSE: To evaluate the long-term prognosis of the fellow-eye in patients with age-related macular degeneration (AMD) who underwent pars plana vitrectomy (PPV) with submacular tissue plasminogen activator injection (SM-tPA) for significant submacular hemorrhage.<br><br>METHODS: Retrospective single-center cohort study including all consecutive patients who underwent PPV with SM-tPA for AMD-related submacular hemorrhage (SMH) between 2010 and 2022, with a minimum follow-up of 2 years. Data was collected from electronic medical records and included demographic characteristics, visual acuity, optical coherence tomography findings, adverse events, further ocular diagnoses in the fellow-eye.<br><br>RESULTS: Forty-seven patients (57% male; mean age 80 years) were included, with a mean follow-up of 82 months. At baseline, most patients had AMD in the fellow-eye (62% dry-AMD; 30% wet-AMD). During follow-up, AMD progressed in 64% of the patients who did not have wet-AMD in their fellow eye at the time of presentation. Seven patients (15%) experienced SMH in the fellow-eye within 1 month to 5 years after initial surgery. The mean VA of the fellow-eye at presentation was 0.64 LogMAR, with a nonsignificant improvement in the first two years. Subsequently, a statistically significant VA deterioration was observed (final mean VA 0.8 LogMAR, p=0.009). By the final follow-up, 30% of patients had better VA in the operated eye, and 26% were legally blind in the fellow-eye.<br><br>CONCLUSION: Patients treated with SM-tPA are at high risk for AMD progression and vision loss in the fellow-eye. Close monitoring of the fellow eye is warranted, and treatment decisions for the involved eye should not be based solely on good fellow-eye vision, given the long-term risk of deterioration.},
}
@article {pmid40838197,
year = {2025},
author = {Lam, BL and Zak, V and Gonzalez, VH and Gregori, NZ and Chavala, SH and Batabyal, S and Carlson, M and Kim, S and Ayyagari, A and Chang, J and Lane, H and Choudry, N and Koester, J and Von Tress, M and Piltz-Seymour, J and Sharif, NA and Tsang, SH and Mahajan, VB and Boyer, DS and Ho, AC and Barone, SB and Mohanty, SK},
title = {Safety and efficacy of MCO-010 optogenetic therapy in patients with Stargardt disease in USA (STARLIGHT): an open-label multi-center Ph2 trial.},
journal = {EClinicalMedicine},
volume = {87},
number = {},
pages = {103430},
pmid = {40838197},
issn = {2589-5370},
abstract = {BACKGROUND: Stargardt disease (SD) is an inherited degenerative retinal disease affecting rod and cone photoreceptors and retinal pigment epithelial (RPE) cells, leading to severe and irreversible vision loss. Optogenetics is a promising approach to restoring vision by photosensitizing spared healthy retinal neurons.<br><br>METHODS: The STARLIGHT phase 2 open-label study (NCT05417126) was conducted over 48-weeks at two US sites to assess the safety and efficacy of MCO-010 administered via a single intravitreal injection in the worse-seeing eye of SD patients. The study began on July 5, 2022, and was completed on September 28, 2023. MCO-010 targets bipolar cells rather than retinal ganglion cells (RGCs) to utilize more abundant cells that respond to ambient light while preserving natural visual processing pathways after treatment. Six adults (mean age 50 years, range 32-71 years, four males and two females) received 1.2E11 genome copies (gc)/eye of MCO-010. The primary outcome was the incidence, nature, severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), intraocular inflammation, retinal thickness, best-corrected visual acuity (BCVA), and lesion size. Secondary endpoints included change in BCVA, vision-guided mobility, and shape determination accuracy. Visual field perimetry and Michigan Retinal Degeneration Questionnaire (MRDQ) were exploratory endpoints.<br><br>FINDINGS: All six participants had at least one ocular TEAE; non-ocular TEAEs occurred in three participants. The most common TEAEs were conjunctival hemorrhage, ocular hypertension, and vitreous cells (two subjects). There were no deaths, hospitalization, loss of eye, retinal detachment, endophthalmitis, or TEAEs leading to study discontinuation. The BCVA (mean &#xb1; SD) of the six treated eyes at baseline and 48-week follow-up was 22.8 &#xb1; 9.87 (range 9-35), and 28.3 &#xb1; 13.28 (range 4-42) ETDRS letters, respectively. The BCVA change from baseline was 7.2 &#xb1; 11.74, 4.2 &#xb1; 14.81, and 5.5 &#xb1; 12.29 at 12, 24, and 48 weeks, respectively. With a wearable magnifier (low-vision glasses), the BCVA change was 17.8 &#xb1; 13.35, 15.7 &#xb1; 17.37, 13.3 &#xb1; 21.37 at 12, 24, and 48 weeks, respectively. The improvement in mean defect in visual field perimetry was 1.02 &#xb1; 3.54, 2.47 &#xb1; 5.00, and 2.63 &#xb1; 5.26 dB at 12, 24, and 48 weeks, respectively. Specific improvements were noted in reading, and color, and contrast domains of the MRDQ.<br><br>INTERPRETATION: MCO-010 optogenetic phase 2 results support further investigation for treatment SD. To our knowledge, this is the first report of improving on(eye)-chart vision of SD participants utilizing optogenetics.<br><br>FUNDING: Nanoscope Therapeutics Inc.},
}
@article {pmid40837592,
year = {2025},
author = {Lanzetta, P and Korobelnik, JF and Heier, JS and Leal, S and Holz, FG and Clark, WL and Eichenbaum, D and Iida, T and Sun, X and Berliner, AJ and Schulze, A and Schmelter, T and Schmidt-Ott, U and Zhang, X and Vitti, R and Chu, KW and Reed, K and Rao, R and Bhore, R and Cheng, Y and Wong, TY},
title = {Plain language summary of publication of the 48-week results from the PULSAR study investigating how well a new dose of aflibercept works and how safe it is for people with wet age-related macular degeneration.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414251356388},
doi = {10.1177/25158414251356388},
pmid = {40837592},
issn = {2515-8414},
abstract = {What is this summary about? • This is a summary of a publication about the PULSAR study, which was published in The Lancet scientific journal. • Wet age-related macular degeneration (or AMD) is a long-term eye disease in which abnormal blood vessels grow in the back of the eye. As these vessels leak fluid or blood, the word "wet" is part of the disease name. This affects the central part of a person's vision, which can make it hard for people to read, drive, or perform other daily activities. It is one of the main causes of visual loss in older people, and if it is left untreated, it can lead to rapid loss of vision. • People with wet AMD can be treated with anti-vascular endothelial growth factor (or anti-VEGF) medicine, given as an injection into the back of the eye. This type of medicine can improve vision by directly reducing the leakage into the macula and by stopping the growth of new, abnormal blood vessels. This leads to reduced swelling of the macula, which is measured by central retinal thickness. These therapies need frequent eye injections. One of the biggest difficulties for many people and their caregivers is that they need to keep up with visits for their injections that are often required to maintain good vision. • Aflibercept is an anti-VEGF medicine that health authorities across different countries have approved for the treatment of wet AMD, as well as other eye diseases, which we will not discuss in this material. People with wet AMD can receive injections of aflibercept 2 mg, given initially once per month for three months. After that, people usually receive treatment every 8 weeks, or sometimes less frequently, depending on their doctors' assessments of the disease state. • The PULSAR study was carried out to see if a higher, 8 mg, dose of aflibercept would provide the same treatment results as aflibercept 2 mg, but with the need for fewer injections. If fewer injections are necessary, this can potentially help patients and their caregivers keep up with treatment. • The PULSAR study involved a direct comparison of the two doses of this anti-VEGF medicine in patients with wet AMD who were placed into one of three treatment groups with different dosing intervals at random. What were the results? • Through the first year (or 48 weeks), participants who received injections of aflibercept 8 mg every 12 or 16 weeks after an injection once per month for three months, had improvements in vision that were similar to those of participants treated with aflibercept 2 mg every 8 weeks. • After the injection once per month for three months, at Week 16, there were fewer participants treated with the 8 mg dose who had abnormal fluid leakage in the macula compared to the 2 mg dose. • At Week 48, participants who received aflibercept 8 mg had similar decreases in the thickness of the retina in the central region as those treated with aflibercept 2 mg. • Most participants who received aflibercept 8 mg and completed 48 weeks of the study maintained their 12- or 16-week injection schedules, without needing to shorten the interval between injections. • Adverse events in participants treated with aflibercept 8 mg were also similar to those in participants treated with aflibercept 2 mg. What do the results mean? • Findings show that aflibercept 8 mg can improve vision to the same extent as aflibercept 2 mg in people with wet AMD, but with fewer injections than aflibercept 2 mg so that people can potentially keep up with their treatments more easily.},
}
@article {pmid40837450,
year = {2025},
author = {George, LM and Ranjana, M and Quinodoz, M and Tang, RWC and Lim, WK and Gilhar, NG and Farooqui, SZ and Rivolta, C and Fenner, BJ},
title = {Early-onset macular drusen, a monogenic form of age-related macular degeneration.},
journal = {American journal of ophthalmology case reports},
volume = {39},
number = {},
pages = {102408},
pmid = {40837450},
issn = {2451-9936},
}
@article {pmid40837411,
year = {2025},
author = {Hao, X and Du, L and Liu, G and Li, Z and Wang, S},
title = {Human retinal organoids for modelling dry age-related macular degeneration and screening drugs.},
journal = {Genes &amp; diseases},
volume = {12},
number = {6},
pages = {101593},
pmid = {40837411},
issn = {2352-3042},
abstract = {Age-related macular degeneration (AMD) poses a significant threat to the vision of the elderly population globally. Unfortunately, there is no effective treatment available for dry AMD. In this study, we utilized human retinal organoids (ROs) stimulated with sodium iodate to establish a model for dry AMD. We assessed the apoptosis of retinal organoid cells and conducted RNA sequencing to analyze molecular changes. Our findings indicate that metformin and the fetal hemoglobin (HbF) inducer TN1 could protect ROs from sodium iodate induced damage and restore retinal function in murine model. The administration of metformin and TN1 alleviated apoptosis in ROs and improved visual function. Studies of molecular mechanisms indicated that the protective effects of metformin and TN1 may be related to the HMOX1 gene, providing valuable insights for the development of new therapies for dry AMD via targeting HMOX1 and its downstream pathways.},
}
@article {pmid40837344,
year = {2025},
author = {Walia, S and Morya, AK and Khullar, S and Aggarwal, S and Kaur, R},
title = {Role of alternative oral therapy for the management of wet age-related macular degeneration and proliferative diabetic retinopathy.},
journal = {World journal of diabetes},
volume = {16},
number = {8},
pages = {109231},
pmid = {40837344},
issn = {1948-9358},
abstract = {Proliferative diabetic retinopathy (PDR) affects approximately 6% of diabetic patients globally. The overall prevalence of diabetic retinopathy is around 22%. Wet age-related macular degeneration (ARMD), the sight-threatening type of ARMD, affects approximately 1.2%-1.3% of the general population and represents 15% of total ARMD cases. While intravitreal anti-vascular endothelial growth factor injections are still the mainstay therapy, there are a few challenges, such as frequent administration, cost burden, and compliance barriers that prompt the need for exploration into systemic oral alternative drugs like fenofibrate, candesartan, and vorolanib. These oral therapies have the advantage of being non-invasive and systemically accessible with few logistical burdens. This review highlights current evidence supporting the use of oral therapies in PDR and wet ARMD management, along with practical limitations and future prospects.},
}
@article {pmid40837068,
year = {2025},
author = {Mukherjee, S and Vance, E and von der Emde, L and Arunachalam, T and De Silva, T and Thavikulwat, AT and Orndahl, C and Nyaiburi, C and Abraham, M and Hammel, K and Sadda, SR and Chew, EY and Pfau, M and Wong, WT and Jeffrey, BG and Keenan, TDL},
title = {Variation in Mesopic Retinal Sensitivity Relative to Distance from Geographic Atrophy in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100879},
pmid = {40837068},
issn = {2666-9145},
abstract = {PURPOSE: To analyze the relationship between distance from geographic atrophy (GA) lesion borders and mesopic retinal sensitivity in age-related macular degeneration (AMD).<br><br>DESIGN: Exploratory analyses of the longitudinal microperimetry dataset from a recent phase II, prospective, single-arm, nonrandomized trial of oral minocycline for GA progression.<br><br>PARTICIPANTS: Individuals with GA from AMD in &#x2265;1 eye.<br><br>METHODS: Mesopic retinal sensitivity was assessed longitudinally with a fundus-guided microperimetry device at baseline, month 3, and every 6 months thereafter, using a custom T-shaped test pattern centered on the fovea. Individual test loci were superimposed on an aligned fundus autofluorescence image and distance from the closest GA lesion border (GA distance) was computed. The relationship between GA distance and retinal sensitivity was analyzed in study eyes using repeated-measures regression.<br><br>MAIN OUTCOME MEASURES: Mesopic retinal sensitivity.<br><br>RESULTS: The study population comprised 26 study eyes from 26 participants (mean age 74.2 years). Retinal sensitivity of extralesional testing loci increased steeply, as a quadratic function, between 0&#xb0; and 2.05&#xb0; (i.e., knot at 2.05&#xb0;; 95% confidence interval [CI] 1.26&#xb0;-2.84&#xb0;) of GA distance. Beyond 2.05&#xb0;, it increased linearly and less steeply. In nonlinear analyses accounting for nesting, a significant effect of GA distance on retinal sensitivity was observed. For GA distances <2.05&#xb0;, sensitivity increased quadratically by approximately 1.99 decibels (dB)/&#xb0; (95% CI: 1.15, 2.83 dB/&#xb0;; P < 0.001) or higher. For GA distances &#x2265;2.05&#xb0;, sensitivity increased at 0.56 dB/&#xb0; (95% CI: 0.42, 0.70 dB/&#xb0;; P < 0.001). There was also a significant effect of time on sensitivity (estimate: -0.07 dB/month; 95% CI: -0.08, -0.06 dB/month; P < 0.001).<br><br>CONCLUSIONS: The results demonstrate a perilesional zone 2&#xb0; (&#x223c;580 &#x3bc;m) around the GA border in which retinal sensitivity changes steeply according to GA distance. This zone presents an important focus for closer evaluation in interventional studies examining potential efficacy for the preservation or recovery of retinal function. With GA progression, decreased retinal sensitivity expands ahead of GA expansion itself, as an advancing wave. Overall, the degree and extent of decreased visual function beyond GA borders have important implications for the design of clinical trials, decision-making in clinical practice, and insights into AMD pathophysiology.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40837066,
year = {2025},
author = {Velaga, SB and Alagorie, AR and Nittala, MG and Moore, NC and Song, YE and Haines, J and Pericak-Vance, MA and Stambolian, D and Hu, Z and He, Y and Sadda, SR},
title = {Longitudinal Assessment of Area of Reticular Pseudodrusen in Eyes with Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100881},
pmid = {40837066},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the change in the area of reticular pseudodrusen (RPD) and choroidal thickness over 2 years in eyes with age-related macular degeneration (AMD).<br><br>DESIGN: Longitudinal cohort study.<br><br>SUBJECTS: The study reviewed 1332 eyes from 666 subjects with baseline and 2-year follow-up data, of which 108 eyes were graded to have RPD. Among these, 35 eyes from 22 participants (mean age: 72.8 &#xb1; 8.9 years; range: 50-84; 37% female) were eligible for this analysis because they had early or intermediate AMD with RPD at baseline, absence of geographic atrophy at 2 years, and images that were gradable for the presence of RPD.<br><br>METHODS: Infrared reflectance (IR), blue-light fundus autofluorescence, and spectral-domain OCT were obtained for all subjects at baseline and at 2 years. Using the instrument software, a certified grader delineated the RPD area (mm[2]) on the IR image using the free hand tool. Choroidal thickness was measured for both baseline and month 24 using a previously described deep learning algorithm to compute a choroidal volume.<br><br>MAIN OUTCOME MEASURES: Changes in RPD area (mm[2]) and mean volumetric choroidal thickness (&#x3bc;m) between baseline and 2 years.<br><br>RESULTS: The RPD area increased significantly (P < 0.001) by month 24 compared with baseline with a mean increase of 6.23 &#xb1; 4.64 mm[2]. The mean volumetric choroidal thickness was not significantly different from baseline 182.2 &#xb1; 94.36 (134.20-227.90) to month 24 178.2 &#xb1; 41.10 (109-258).<br><br>CONCLUSIONS: In this longitudinal natural history analysis, we observed an increase in RPD area of >6 mm[2] over 2 years in the absence of a significant change in choroidal thickness. Although AMD eyes with presence of RPD typically have a thinner choroid, the increase in extent of these lesions does not appear to be associated with further thinning of the choroid.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40836128,
year = {2025},
author = {Jin, E and Chan, AC and Thomas, GN},
title = {Efficacy of faricimab secondary to anti-vascular endothelial growth factor agents in patients with neovascular age-related macular degeneration: a systematic review and meta-analysis.},
journal = {Eye (London, England)},
volume = {39},
number = {15},
pages = {2738-2751},
pmid = {40836128},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Ranibizumab/therapeutic use ; Treatment Outcome ; Tomography, Optical Coherence ; Antibodies, Bispecific ; },
abstract = {This study examines the efficacy and safety of faricimab as a secondary treatment for neovascular age-related macular degeneration (nAMD) patients previously treated with anti-vascular endothelial growth factors (anti-VEGF) agents. A literature search was performed on PubMed, EMBASE, and Cochrane Library up to 24 October 2024. Cohort and observational studies reporting functional and anatomical outcomes in nAMD patients switched to faricimab were included. Meta analysis with common and random-effect model was performed using "metagen" package in R version 3.2.1. 446 studies were identified on our preliminary search, of which 20 studies (1007 eyes) with a baseline central macular thickness (CMT) of 342.07 (± 110.14) um were included in the final analysis. Switching to faricimab led to significant reductions in CMT at 3 months (Mean difference = -47.08 um, 95% Confidence Interval (CI)= (-66.01, -28.15), p = 0.009) and 6 months post-switch (Mean difference =-44.68 um, 95% CI= (-67.17, -22.20), p = 0.002). Pigment epithelium detachment (PED) height was also reduced at 3 months (Mean difference = -31.71um, 95% CI= (-45.12, -18.30), p = 0.036) and 6 months post-switch (Mean difference = -34.85 um, 95% CI= (-50.19, -19.51), p = 0.011). However, no significant improvements in best corrected visual acuity (BCVA) were observed at 3 months (p = 0.407), 6 months (p = 0.920) or ≥12 months (p = 0.261) post-switch. Treatment intervals were significantly extended (Mean difference=1.87 weeks, 95% CI = (0.41, 33.3), p = 0.019), with a low incidence of serious adverse events. In conclusion, faricimab demonstrates favorable structural benefits, stable functional outcomes and extended treatment intervals as a second-line treatment for nAMD in patients with prior anti-VEGF therapy.},
}
@article {pmid40835392,
year = {2025},
author = {Shao, Z and Li, A and Lv, J and Yu, C and Pan, L and Pei, P and Yang, L and Chen, Y and Li, Y and Schmidt, D and Barnard, M and Lam, H and Bragg, F and Chen, J and Chen, Z and Li, L and Du, H and Sun, D and , },
title = {Patterns and correlates of visual impairment and ocular hypertension among older adults in the general Chinese population: results from the CKB Biobank.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2024-326620},
pmid = {40835392},
issn = {1468-2079},
abstract = {BACKGROUND: While numerous ophthalmology-specific cohort studies have been conducted in China, there is a significant lack of comprehensive, population-based study on the potential determinants of visual impairment and ocular hypertension (OHT) in the general Chinese population.<br><br>METHODS: In the 2020-2021 resurvey of the China Kadoorie Biobank study, ~25 000 randomly selected participants from 10 diverse localities (5 urban and 5 rural) were surveyed. Presenting visual acuity (PVA) was measured using the Random E eye chart and intraocular pressure (IOP) was measured using a handheld Icare (ic100) tonometer. Associations of sociodemographic and other factors with risks of visual impairment and OHT were examined using multivariable logistic regression.<br><br>RESULTS: Among the 24 613 (aged 45-95 years, 64.4%&#x2009;women) participants, 21.8% had visual impairment (PVA <0.50) and 18.4% had OHT (IOP >18.6&#x2009;mm Hg). The prevalence rate of visual impairment increased dramatically with age (49.3% in those &#x2265;75 years vs 8.9% in those <55 years), but an opposite trend was observed for OHT. Risks of these two eye conditions were both inversely associated with household income and fish consumption but positively with systolic blood pressure and blood glucose. Higher education was associated with a higher OHT risk but not with visual impairment. Body mass index was inversely associated with visual impairment but positively with OHT. Age-related macular degeneration and glaucoma were most strongly associated with risk of visual impairment, followed by cataract.<br><br>CONCLUSION: The relatively high prevalence rates of poor vision and OHT in China suggest that well-targeted public health interventions should be developed.},
}
@article {pmid40835159,
year = {2025},
author = {Dettoraki, M and Vandorou, KT and Tsoukalas, D and Basagianni, E and Chatziralli, I and Theodossiadis, P and Loukides, S and Toumpanakis, D},
title = {Ocular manifestations in COPD patients. An underrecognized comorbidity.},
journal = {Respiratory medicine},
volume = {247},
number = {},
pages = {108313},
doi = {10.1016/j.rmed.2025.108313},
pmid = {40835159},
issn = {1532-3064},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/complications/epidemiology/physiopathology ; *Eye Diseases/epidemiology/etiology ; Comorbidity ; Cardiovascular Diseases/epidemiology ; Quality of Life ; },
abstract = {Chronic obstructive pulmonary disease (COPD) is characterized by the presence of comorbidities, such as cardiovascular diseases, that significantly impact symptoms, quality of life and prognosis. Indeed, it is shown that patients with COPD may present with diseases of aging, earlier in life, including eye disorders, such as macular degeneration and cataract. Although underrecognized, cumulative evidence over the last years suggests that COPD is associated with ocular abnormalities, mainly in the posterior segment of the eye, affecting both the microvascular network of the retina and the optic nerve, while structural abnormalities of the choroid and cornea have also been described. Thus, the aim of this review is to provide a comprehensive description of the evidence for ocular findings in patients with COPD that is an underrecognized entity and co-morbidity. A secondary aim of this review is to introduce pulmonologists to current ophthalmological techniques that may foster both clinical practice and research, especially through the assessment of the ocular microvascular network that is closely related to cardiovascular comorbidities.},
}
@article {pmid40833455,
year = {2025},
author = {Lupidi, M and Bandello, F and Vujosevic, S and Parravano, M and Bacherini, D and Minnella, AM and Giansanti, F and Ascardi, C and Staurenghi, G},
title = {Multimodal Imaging to Assess Disease Activity and Predict Fluid Resolution in Patients with wAMD Treated with Brolucizumab: The IMAGINE Study.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {10},
pages = {2497-2510},
pmid = {40833455},
issn = {2193-8245},
abstract = {BACKGROUND: This prospective, open-label, single-arm, multicenter phase IV study (NCT04774926) evaluated early imaging parameters as predictors of long-term fluid resolution and assessed the efficacy and safety of brolucizumab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in a real-world Italian setting.<br><br>PATIENTS AND METHODS: A total of 122 patients aged&#x2009;&#x2265;&#x2009;50&#xa0;years with subfoveal macular neovascularization secondary to wAMD were enrolled. All patients were anti-vascular endothelial growth factor (anti-VEGF)- and investigational treatment-na&#xef;ve. Brolucizumab (6&#xa0;mg) was administered intravitreally at baseline and weeks 4 and 8, followed by maintenance dosing every 12&#xa0;weeks (q12w) or 8&#xa0;weeks, on the basis of disease activity. Imaging modalities included spectral-domain optical coherence tomography (OCT), OCT angiography, fluorescein angiography, and indocyanine green angiography. Disease activity was assessed using anatomical and functional parameters.<br><br>RESULTS: No significant predictive anatomical biomarkers for fluid-free status were identified. At week 48, 22.5% of patients achieved q12w fluid-free status. Significant reductions in central subfield thickness were observed, with a median change of -143.0&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.0001). Median best-corrected visual acuity improved by 5.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline (p&#x2009;<&#x2009;0.0001). Ocular adverse events were consistent with the known safety profile of brolucizumab.<br><br>CONCLUSIONS: Brolucizumab demonstrated effectiveness and safety in a real-world wAMD cohort, aligning with findings from randomized trials. Although no predictive biomarkers were identified, results emphasize the role of multimodal imaging in guiding individualized treatment strategies and highlight variability in patient responses.<br><br>GOV ID: NCT04774926.},
}
@article {pmid40832922,
year = {2025},
author = {Katschke, KJ and Truong, T and Pham, V and Xi, H and Tang, W and Gu, X and Teotia, P and Hofmann, JW and Chaney, SY and Kirchhofer, D and van Lookeren Campagne, M and Jeanne, M},
title = {HTRA1-dependent proteolysis induces age-related retinal degeneration and exacerbates choroidal neovascularization.},
journal = {Disease models &amp; mechanisms},
volume = {18},
number = {10},
pages = {},
pmid = {40832922},
issn = {1754-8411},
support = {//Genentech/ ; },
mesh = {Animals ; High-Temperature Requirement A Serine Peptidase 1 ; *Choroidal Neovascularization/pathology/enzymology/complications ; *Retinal Degeneration/pathology/enzymology/complications ; Retinal Pigment Epithelium/pathology/metabolism ; Humans ; *Proteolysis ; *Serine Endopeptidases/metabolism ; *Aging/pathology ; Mice ; Macular Degeneration/pathology ; Mice, Inbred C57BL ; Photoreceptor Cells, Vertebrate/pathology/metabolism ; Photoreceptor Cells/pathology/metabolism ; Inflammation/pathology ; },
abstract = {Polymorphisms in the ARMS2/HTRA1 locus on chromosome 10 enhance the risk of geographic atrophy and macular neovascularization, the advanced forms of age-related macular degeneration (AMD). Although HTRA1 mutations have been associated with microvascular defects in the brain, it remains unclear whether changes in HTRA1 expression contribute to AMD pathophysiology. In this study, we showed that, in AMD donor eyes, HTRA1 protein accumulated around the retinal pigment epithelium (RPE)/photoreceptor lesions. We then demonstrated that overexpression of catalytically active, but not catalytically inactive, HTRA1 in RPE cells in mice induced age-dependent loss of photoreceptors, inflammation and a decline in photoreceptor functional responses. This retinal degeneration was not exacerbated when the mice were exposed to phototoxic stress in the constant light exposure preclinical model. However, mice overexpressing catalytically active HTRA1 had significant exacerbation of laser-induced choroidal neovascularization lesions. Finally, as substrate processing may define the molecular basis for HTRA1-induced retinal degeneration, we initiated a proteomics approach and identified the visual cycle key player RBP3 as a disease-relevant HTRA1 substrate in the retina.},
}
@article {pmid40830492,
year = {2025},
author = {Chen, J and Long, Z and Shi, D and Zhang, Q and Peng, H},
title = {Ferroptosis-related hub genes and immune cell dynamics as diagnostic biomarkers in age-related macular degeneration.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {777},
pmid = {40830492},
issn = {2047-783X},
support = {81670881//This study received funding from the National Natural Science Foundation of China/ ; },
mesh = {*Ferroptosis/genetics ; Humans ; *Macular Degeneration/genetics/diagnosis/immunology ; Animals ; Biomarkers/metabolism ; Mice ; Gene Expression Profiling ; Transcriptome ; },
abstract = {BACKGROUND: Age-related Macular Degeneration (AMD) is widely acknowledged as a principal cause of vision loss in the elderly. Currently, the therapeutic interventions available in clinical practice fail to achieve satisfactory outcomes. Therefore, it is imperative that we approach the progress of AMD from novel perspectives in order to explore new therapeutic strategies.<br><br>METHOD: We obtained transcriptomic data from the macular and the peripheral retina from patients with AMD and a control group from the&#xa0;Gene Expression Omnibus (GEO) database. Through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we identified differentially expressed genes&#xa0;(DEGs) that were significantly enriched in functions associated with ferroptosis. Subsequent application of machine learning techniques enabled the identification of key hub genes, whose diagnostic potential was further validated. Additionally, the expression of these hub genes was corroborated in both animal and cellular models. Finally, we performed a functional enrichment analysis of these hub genes.<br><br>RESULTS: In the macula of patients with AMD, 452 DEGs were identified, while in the peripheral retina, 222 DEGs were discovered. Within the macula, 19 genes were associated with ferroptosis, compared to 3 in the peripheral retina. Consequently, the macular was selected as the primary focus of the study. Subsequent screening of these 19 genes using LASSO regression, Support Vector Machine (SVM), and Random Forest algorithms identified four hub genes: FADS1, TFAP2A, AKR1C3, and TTPA. Consequently, we utilized cigarette smoke extract (CSE) to either stimulate retinal pigment epithelial (RPE) cells in vitro or administer it via intravitreal injection, thereby establishing in vitro and in vivo models of AMD. Results from RT-PCR and Western blot analyses revealed an upregulation of FADS1, AKR1C3, and TTPA, while TFAP2A exhibited decreased expression. Finally, we investigated the infiltration of immune cells within the macular and performed a functional enrichment analysis of the hub genes.<br><br>CONCLUSION: We identified four key ferroptosis-related genes (FRGs)-FADS1, AKR1C3, TFAP2A, and TTPA-that possess diagnostic relevance for AMD and correlate with immune cell infiltration. Moreover, significant changes in both mRNA and protein expression levels of these genes have been observed in in vitro experiments and mice models.},
}
@article {pmid40830295,
year = {2025},
author = {Liu, F and Li, Q and Yang, Y and Lu, F},
title = {Advances in Stem Cell Therapies for Ocular Diseases: Progress in Clinical Trials and Future Perspectives.},
journal = {Stem cell reviews and reports},
volume = {21},
number = {8},
pages = {2386-2406},
pmid = {40830295},
issn = {2629-3277},
support = {82201210//National Natural Science Foundation of China/ ; 82222030//National Natural Science Foundation of China/ ; 2023NSFSC1660//Sichuan Science and Technology Program/ ; 2024HXBH082//Postdoctor Research Fund of West China Hospital, Sichuan University/ ; 2023YFC3403300//National Key Research and Development Program of China/ ; ZYYC23009//1.3.5 project for disciplines of excellence from West China Hospital of Sichuan University/ ; },
mesh = {Humans ; *Eye Diseases/therapy ; *Stem Cell Transplantation/methods/trends ; Clinical Trials as Topic ; Animals ; Macular Degeneration/therapy ; Cell Differentiation ; },
abstract = {Stem cell-based therapies hold promise for vision-threatening ocular diseases by promoting tissue repair and restoring visual function. Stem cells are classified by differentiation potential into two main types. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), possess the capacity to differentiate into somatic cells. Multipotent adult stem cells, such as mesenchymal stem cells (MSCs), are restricted to differentiating into cell types within specific lineages. The therapeutic potential of stem cells is discussed in the context of treating corneal diseases, glaucoma, and retinal disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). This review focuses on the clinical trials of stem cell therapies for ocular diseases and discusses prospects in the field. Despite the considerable promise of these preclinical results in restoring visual function, significant challenges in clinical application remain, such as insufficient long-term cell survival, incomplete functional integration into host tissues, and the potential risk of oncogenic transformation. Future progress will depend on the development of standardized protocols, efficient delivery methods, and interdisciplinary collaboration to effectively translate preclinical advances into clinical applications.},
}
@article {pmid40830259,
year = {2025},
author = {Holland, R and Taylor, TRP and Holmes, C and Riedl, S and Mai, J and Patsiamanidi, M and Mitsopoulou, D and Hager, P and Müller, P and Paetzold, JC and Scholl, HPN and Bogunović, H and Schmidt-Erfurth, U and Rueckert, D and Sivaprasad, S and Lotery, AJ and Menten, MJ and , },
title = {Specialized curricula for training vision language models in retinal image analysis.},
journal = {NPJ digital medicine},
volume = {8},
number = {1},
pages = {532},
pmid = {40830259},
issn = {2398-6352},
support = {/WT_/Wellcome Trust/United Kingdom ; 210572/Z/18/Z//Wellcome Trust Collaborative Award/ ; },
abstract = {Clinicians spend significant time reviewing medical images and transcribing findings. By integrating visual and textual data, foundation models have the potential to reduce workloads and boost efficiency, yet their practical clinical value remains uncertain. In this study, we find that OpenAI's ChatGPT-4o and two medical vision-language models (VLMs) significantly underperform ophthalmologists in key tasks for age-related macular degeneration (AMD). To address this, we developed a dedicated training curriculum, designed by domain specialists, to optimize VLMs for tasks related to clinical decision making. The resulting model, RetinaVLM-Specialist, significantly outperforms foundation medical VLMs and ChatGPT-4o in AMD disease staging (F1: 0.63 vs. 0.33) and referral (0.67 vs. 0.50), achieving performance comparable to junior ophthalmologists. In a reader study, two senior ophthalmologists confirmed that RetinaVLM's reports were substantially more accurate than those written by ChatGPT-4o (64.3% vs. 14.3%). Overall, our curriculum-based approach offers a blueprint for adapting foundation models to real-world medical applications.},
}
@article {pmid40830152,
year = {2025},
author = {Goldbach, F and Gerendas, BS and Leingang, O and Alten, T and Bampoulidis, A and Brugger, J and Bogunovic, H and Sadeghipour, A and Schmidt-Erfurth, U},
title = {Human expert grading versus automated quantification of fluid volumes in nAMD, DME and BRVO.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30414},
pmid = {40830152},
issn = {2045-2322},
mesh = {Humans ; *Macular Edema/diagnostic imaging/pathology ; *Diabetic Retinopathy/diagnostic imaging/pathology ; Tomography, Optical Coherence/methods ; Deep Learning ; *Subretinal Fluid/diagnostic imaging ; *Retinal Vein Occlusion/diagnostic imaging/pathology ; Female ; Male ; Aged ; Algorithms ; *Macular Degeneration/diagnostic imaging/pathology ; },
abstract = {This study compared an automated deep learning algorithm with certified human graders from the Vienna Reading Center (VRC) in identifying intra- (IRF) and subretinal fluid (SRF) in OCT scans of patients treated for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME) and branch retinal vein occlusion (BRVO). Multicenter clinical trial data from the VRC imaging database was used for this post hoc analysis. OCT scans were analyzed using a validated algorithm (RetInSight, Vienna, Austria) to compute IRF and SRF volumes. These fluid volumes were compared to fluid presence graded by trained and experienced graders of the VRC. 6898 OCT scans were analyzed for fluid volumes and presence of IRF and SRF. For nAMD/DME /BRVO in the central millimeter: the overall concordance for the detection of IRF and SRF between the algorithm and manual grading reached an AUC of 0.94/0.92/0.98 and 0.89/0.95/0.92, respectively. This deep learning approach showed a high concordance with human expert grading for detection of IRF and SRF and provides precise volumetric information across different retinal fluid-associated diseases. Thus, automated fluid quantification is a feasible tool for standardized treatment decision support and disease monitoring in clinical practice at the highest human expert level.},
}
@article {pmid40830052,
year = {2025},
author = {Lylyk, P and Lylyk, I and Lylyk, PN and Bleise, C and Scrivano, E and Lundquist, J and Nella-Castro, R and Perez, N and Franco, J and Calhoun, MW and Wilbur, LR and Rosenfeld, PJ and Saravia, MJ},
title = {Ophthalmic artery angioplasty in a cohort of patients with geographic atrophy secondary to non-exudative age-related macular degeneration.},
journal = {Journal of neurointerventional surgery},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnis-2025-023608},
pmid = {40830052},
issn = {1759-8486},
abstract = {BACKGROUND: There is increasing evidence that vascular disease and chronic perfusion deficits play a role in the progression of age-related macular degeneration (AMD). This controlled clinical study evaluated the safety and feasibility of treating patients with late-stage AMD and associated geographic atrophy (GA). In addition, exploratory endpoints evaluated the potential to disrupt the disease process and initiate functional changes.<br><br>METHODS: A total of 17 subjects with confirmed late-stage AMD with GA, ophthalmic artery stenosis, and systemic stability were enrolled in this prospective multicenter study. Eleven (64.7%) of these subjects were successfully treated with ophthalmic artery angioplasty using an investigational ophthalmic percutaneous transluminal catheter system designed for this novel anatomical target and indication for use. Primary endpoints included procedure-related complications and procedural feasibility. All exploratory analyses were focused on ophthalmic outcomes and assessed for potential efficacy in choroidal thickness, visual acuity, reading ability, and patient-reported outcomes. Treated subjects were followed for 3 months by the interventional neuroradiology site and for 6 months by the ophthalmology site.<br><br>RESULTS: All systemic procedure-related adverse events (AEs) were potentially expected, effectively treated, resolved without sequelae, and included bronchial abrasion and hemoptysis secondary to intubation, urinary tract infection secondary to urinary catheterization, and vascular access site inflammation and hematoma. Procedure-related ocular AEs (eg, suspected retinal microemboli and potential reperfusion injury) were asymptomatic, graded as mild, and resolved without treatment or sequelae. Mean (SD) primary lesion stenoses decreased 59% from 43.7 (14.25)% to 18.2 (12.09)%. At study exit, mean best-corrected visual acuity improved by 6.7 letters (P=0.003) over baseline, and reading ability results improved 3.4%, 5.1%, and 28.5% (P=0.03) over baseline for reading acuity, critical print size, and reading speed, respectively. Patient-reported outcomes showed improvements in mobility and independence and in reading and accessing information.<br><br>CONCLUSIONS: The feasibility of ophthalmic artery angioplasty in this population was demonstrated with the investigational devices, while providing an acceptable safety profile. Efficacy and functional improvement were also seen, providing guidance for future study.},
}
@article {pmid40829697,
year = {2025},
author = {Hussain, ZS and Chauhan, MZ and Muayad, J and Loya, A and Nembhard, W and Sallam, AB},
title = {Potency Matters: The Role of Statin Intensity in Modulating Risk for Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {280},
number = {},
pages = {326-333},
doi = {10.1016/j.ajo.2025.08.024},
pmid = {40829697},
issn = {1879-1891},
mesh = {Humans ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration &amp; dosage ; Retrospective Studies ; Female ; Male ; Aged ; *Macular Degeneration/epidemiology/prevention &amp; control ; Middle Aged ; *Dyslipidemias/drug therapy/complications ; Risk Factors ; Diabetes Mellitus, Type 2/complications ; Incidence ; Propensity Score ; Aged, 80 and over ; Adult ; Follow-Up Studies ; United States/epidemiology ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of vision loss. Statins, primarily used for cardiovascular disease prevention, may have pleiotropic effects on AMD, but existing evidence is inconclusive. This study investigated the association between statin intensity (high, moderate, low) and the risk of AMD in patients with type 2 diabetes and dyslipidemia.<br><br>DESIGN: A retrospective clinical cohort study using de-identified electronic health records from the US Collaborative Network.<br><br>METHODS: Adults aged 40 years or older with type 2 diabetes, dyslipidemia, and at least 1 ophthalmologic visit were included from 2014 to 2024 Patients with confounding conditions (liver disease, HIV, etc.) and prior AMD diagnoses were excluded. Propensity score matching was used to balance covariates between statin intensity cohorts and a treatment-na&#xef;ve control group. Intensity groups included: high-intensity statin therapy (rosuvastatin 20-40 mg or atorvastatin 40-80 mg), high-intensity-na&#xef;ve, medium-intensity statin therapy (rosuvastatin [5 mg, 10 mg], simvastatin [20 mg, 40 mg], fluvastatin [80 mg], pravastatin [40 mg, 80 mg], lovastatin [40 mg], atorvastatin [10 mg, 20 mg], or pitavastatin [1 mg, 2 mg, 4 mg]), and low-intensity statin therapy (simvastatin 5-10 mg, pravastatin 10-20 mg, lovastatin 10-20 mg, or fluvastatin 20-40 mg).<br><br>MAIN OUTCOME MEASURES: Incidence of combined AMD (nonexudative and exudative), nonexudative AMD, exudative AMD, and all-cause mortality at 6 months, 1 year, 3 years, and 5 years after the index event. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazard regression models.<br><br>RESULTS: After matching, a total of 20 282 patients were included. High-intensity statin use was associated with a reduced risk of combined AMD at 3 and 5 years (HR: 0.74 (95% CI: 0.57-094) and 0.79 (95% CI: 0.62-0.98), respectively). Medium-intensity statin therapy was associated with a significantly lower risk of combined AMD (HR range: 0.49 [95% CI 0.55-0.91] to 0.77 [95% CI: 0.60-0.98]) and exudative AMD (HR range: 0.19 [0.06-0.054] to 0.62 [95% CI: 0.40-0.96]) at all follow-up points. All statin intensities were associated with reduced all-cause mortality.<br><br>CONCLUSIONS: In this study of patients with type 2 diabetes and dyslipidemia, medium- and high-intensity, but not low-intensity, statin therapies were associated with a reduced risk of AMD. Further research is needed to confirm these findings and elucidate the underlying mechanisms.},
}
@article {pmid40828709,
year = {2025},
author = {Chen, T and Zhang, D and Chen, D and Fu, H and Jin, K and Wang, S and Cohen, LD and Zhao, Y and Yi, Q and Zhang, J},
title = {Neovascularization Segmentation via a Multilateral Interaction-Enhanced Graph Convolutional Network.},
journal = {IEEE transactions on pattern analysis and machine intelligence},
volume = {47},
number = {12},
pages = {11107-11123},
doi = {10.1109/TPAMI.2025.3600335},
pmid = {40828709},
issn = {1939-3539},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; Algorithms ; *Neural Networks, Computer ; Databases, Factual ; },
abstract = {Choroidal neovascularization (CNV), a primary characteristic of wet age-related macular degeneration (wet AMD), represents a leading cause of blindness worldwide. In clinical practice, optical coherence tomography angiography (OCTA) is commonly used for studying CNV-related pathological changes, due to its micron-level resolution and non-invasive nature. Thus, accurate segmentation of CNV regions and vessels in OCTA images is crucial for clinical assessment of wet AMD. However, challenges existed due to irregular CNV shapes and imaging limitations like projection artifacts, noises and boundary blurring. Moreover, the lack of publicly available datasets constraints the CNV analysis. To address these challenges, this paper constructs the first publicly accessible CNV dataset (CNVSeg), and proposes a novel multilateral graph convolutional interaction-enhanced CNV segmentation network (MTG-Net). This network integrates both region and vessel morphological information, exploring semantic and geometric duality constraints within the graph domain. Specifically, MTG-Net consists of a multi-task framework and two graph-based cross-task modules: Multilateral Interaction Graph Reasoning (MIGR) and Multilateral Reinforcement Graph Reasoning (MRGR). The multi-task framework encodes rich geometric features of lesion shapes and surfaces, decoupling the image into three task-specific feature maps. MIGR and MRGR iteratively reason about higher-order relationships across tasks through a graph mechanism, enabling complementary optimization for task-specific objectives. Additionally, an uncertainty-weighted loss is proposed to mitigate the impact of artifacts and noise on segmentation accuracy. Experimental results demonstrate that MTG-Net outperforms existing methods, achieving a Dice socre of 87.21% for region segmentation and 88.12% for vessel segmentation.},
}
@article {pmid40828526,
year = {2025},
author = {Yeh, SI and Ho, TC and Chu, TW and Chen, SL and Ou, R and Tsao, YP},
title = {OBM1701 Alleviates Choroidal Neovascularization in Experimental Animals Via Suppressing the Expression of HIF-1α in Retinal Pigment Epithelial Cells.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {8},
pages = {21},
pmid = {40828526},
issn = {2164-2591},
mesh = {Rats, Inbred BN ; Humans ; Male ; Female ; Animals ; Mice ; Rats ; Mice, Inbred C57BL ; Cell Line ; *Choroidal Neovascularization/drug therapy ; *Peptide Fragments/administration &amp; dosage ; *Retinal Pigment Epithelium/drug effects/metabolism ; Epithelial Cells/drug effects/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Drug Evaluation, Preclinical ; Administration, Ophthalmic ; Swine ; Primary Cell Culture ; Cell Hypoxia ; Lasers, Solid-State ; Vascular Endothelial Growth Factor A/metabolism ; Eye Proteins ; Nerve Growth Factors ; Serpins ; },
abstract = {PURPOSE: OBM1701, a pigment epithelium-derived factor-derived short peptide, can eliminate corneal neovascularization by blocking endothelial cell angiogenesis. Activation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE) is critical for the pathogenesis of choroidal neovascularization (CNV), the hallmark of neovascular age-related macular degeneration (nAMD). Here, the potential inhibitory effect of OBM1701 on laser-induced CNV in animals was investigated.<br><br>METHODS: Two days after the laser injury, topical OBM1701 eye drops were applied once daily for 12 days. Subsequently, CNV vascular leakage and CNV area were measured by fluorescein angiography and isolectin GS-IB4 staining on choroidal/RPE flatmounts, respectively. Immunostaining was used to detect the expression of HIF-1&#x3b1; and vascular endothelial growth factor A (VEGFA) in CNV lesions. In vitro, ARPE-19 cells and primary porcine RPE were exposed to hypoxia mimetic condition by adding dimethyloxalylglycine and oxygen&#xa0;deprivation in&#xa0;cultures, respectively. Then the gene and protein expression of HIF-1&#x3b1; and VEGFA were evaluated by real-time PCR and Western blotting.<br><br>RESULTS: OBM1701 effectively reduced vascular leakage and CNV formation. Meanwhile, OBM1701 treatment blocked the overexpression of HIF-1&#x3b1; and VEGFA in RPE cells located within CNV lesions. In culture, OBM1701 pretreatment suppressed hypoxia-induced HIF-1&#x3b1; and VEGFA expressions.<br><br>CONCLUSIONS: Through animal studies, we demonstrate that OBM1701 has the potential to treat CNV. We also suggest RPE as a drug target for OBM1701 to treat CNV, by attenuating the hypoxia-induced HIF-1&#x3b1;/VEGFA signaling.<br><br>TRANSLATIONAL RELEVANCE: OBM1701 in ophthalmic drop shows the potential to be developed into a novel therapy for the treatment of nAMD.},
}
@article {pmid40828357,
year = {2025},
author = {Kong, Q and Jiang, Y and Li, X and Lu, X},
title = {Regulation of toll-like receptor signaling pathways in age-related eye disease: from mechanisms to targeted therapeutics.},
journal = {Inflammopharmacology},
volume = {33},
number = {9},
pages = {5257-5271},
pmid = {40828357},
issn = {1568-5608},
mesh = {Humans ; *Toll-Like Receptors/metabolism/antagonists &amp; inhibitors ; *Signal Transduction/physiology/drug effects ; Animals ; *Aging/metabolism/pathology ; *Eye Diseases/metabolism/drug therapy ; Inflammation/metabolism ; Dry Eye Syndromes ; },
abstract = {Aging is a significant risk factor for various ophthalmic diseases, which can lead to vision loss. With the worldwide elderly population expanding, it is essential for researchers to elucidate the mechanisms underlying the progression of ocular diseases and to ascertain methods for their prevention or deceleration. The five principal age-related eye disorders (AREDs) consist of glaucoma, dry eye syndrome (DES), diabetic retinopathy (DR), cataracts, and age-related macular degeneration (AMD). A sustained subclinical low-grade inflammation has been observed at the ocular surface of elderly individuals who identify as "healthy." In these instances, an imbalance in para-inflammatory processes, which are essential for preserving tissue homeostasis in response to environmental injuries or insults, results in ocular surface system dysfunction, commonly referred to as InflammAging. Corneal and conjunctival epithelial cells express a variety of immune-related recognition receptors, including toll-like receptors (TLRs). At the ocular surface, TLRs play an active role in immunological instruction and innate defense mechanisms. The function of TLRs in AREDs is summarized here. In addition to discussing potential solutions and challenges in the clinical use of TLR inhibitors, future challenges will also be addressed.},
}
@article {pmid40828189,
year = {2025},
author = {Scampoli, A and Carlà, MM and Grieco, G and Governatori, L and Catalani, R and Rizzo, S and Caporossi, T},
title = {One-year outcomes of faricimab for neovascular age related macular degeneration with OCT angiography: focus on resistant and refractory cases.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {342},
pmid = {40828189},
issn = {1573-2630},
mesh = {Prospective Studies ; Follow-Up Studies ; Treatment Outcome ; *Macular Degeneration/diagnostic imaging/drug therapy/pathology ; Tomography, Optical Coherence/methods ; *Visual Acuity/drug effects ; Biomarkers/analysis ; *Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; *Choroidal Neovascularization/diagnostic imaging/drug therapy/pathology ; Choroid/blood supply/drug effects/pathology ; *Antibodies, Bispecific/administration &amp; dosage ; Fluorescein Angiography/methods ; Macula Lutea/diagnostic imaging/drug effects/pathology ; Humans ; Male ; Female ; Aged ; Aged, 80 and over ; },
abstract = {PURPOSE: To investigate the 12-month effectiveness and safety of intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) resistant to previous anti-VEGF treatment.<br><br>METHODS: Prospective, monocentric study including consecutive patients with resistant/refractory nAMD switched to IVF between July 2023 and November 2024. Primary endpoints were safety, best corrected visual acuity (BCVA), central subfield thickness (CST), and subfoveal choroidal thickness. Secondary endpoints included changes in optical coherence tomography (OCT) and OCT angiography biomarkers: fluid prevalence, pigment epithelial detachment (PED) height, and vascular densities. All patients received four monthly loading doses of faricimab, with subsequent treat-and-extend regimen.<br><br>RESULTS: The study included 30 eyes of 30 patients. Mean follow-up was 14.2&#x2009;&#xb1;&#x2009;1.9&#xa0;months and no adverse events were reported. BCVA significantly improved from 0.77 to 0.62 LogMAR at the end of the study period (p&#x2009;=&#x2009;0.009), with 67% of eyes showing stable vision. CST significantly decreased from baseline (-57&#xa0;&#x3bc;m on average, p&#x2009;<&#x2009;0.001), along with PED height which showed its main decrease during the loading phase. Forty-seven percent of eyes achieved complete macular dryness at week 16, with significant reduction in terms of subretinal fluid (SRF) and intraretinal fluid (IRF) prevalence. At the end of the study, 90% of patients achieved treatment intervals of at least q8w, with 27% of eyes being on q12w. Finally, no changes in superficial/deep vessel densities were observed.<br><br>CONCLUSION: Faricimab demonstrated efficacy and safety in refractory/resistant nAMD, with significant improvements in structural outcomes and stable/improved visual acuity. Extended treatment intervals suggest a potential reduction in treatment burden.},
}
@article {pmid40827631,
year = {2025},
author = {Zhao, X and Xia, W and Wang, Y and Zhang, Y and Zhou, Z and Liu, P and Zhang, S and Zheng, Z and Shen, W and Zhang, S and Yao, J and Sun, T and Jiang, C and Zhao, C},
title = {Intravenous Multifunctional Nanotherapy for Treating Dry Age-Related Macular Degeneration.},
journal = {Advanced healthcare materials},
volume = {14},
number = {29},
pages = {e02925},
doi = {10.1002/adhm.202502925},
pmid = {40827631},
issn = {2192-2659},
support = {82301217//National Natural Science Foundation of China/ ; 81730025//National Natural Science Foundation of China/ ; 82020108006//Science and Technology Commission of Shanghai Municipality/ ; },
mesh = {Animals ; *Sirolimus/pharmacology/chemistry/administration &amp; dosage ; Humans ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Oxidative Stress/drug effects ; *Macular Degeneration/drug therapy/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Mice ; Reactive Oxygen Species/metabolism ; Micelles ; Polyethylene Glycols/chemistry ; *Nanoparticles/chemistry ; Iodates ; },
abstract = {Retinal pigment epithelium (RPE) degeneration is the pathological hallmark of multifactorial dry age-related macular degeneration (dAMD). Mounting evidence implicates oxidative stress and aberrant activation of mammalian target of rapamycin (mTOR) as key drivers of this process. Recent studies have shown that simultaneous modulation of these pathways may offer therapeutic benefit. However, clinical trials of rapamycin, an mTOR inhibitor widely employed in retinal research, have demonstrated limited efficacy, potentially due to poor bioavailability and paradoxical effects on RPE and photoreceptors. To overcome these challenges, APMNP@Rapa, a rapamycin-loaded, methionine-based ROS-responsive polymeric micellar system functionalized with an Ab peptide for active targeting of damaged RPE is developed. The micelles self-assemble from poly(ethylene glycol) - poly-methionine copolymers, leveraging methionine's endogenous nature and innate biocompatibility as an innovative ROS-responsive motif. This design yields particles with exceptional circulation stability and enhanced biocompatibility. In the high-ROS microenvironment of diseased RPE, APMNP@Rapa triggers on-demand rapamycin release. In a sodium iodate (NaIO3)-induced RPE oxidative stress model, APMNP@Rapa simultaneously inhibited aberrant mTOR activation, attenuated oxidative damage, and suppressed inflammatory response. These combined effects resulted in a marked preservation of the retina against degradation. Overall, the research establishes a paradigm for intravenous treatment of dAMD using multifunctional nanotherapy.},
}
@article {pmid40827295,
year = {2025},
author = {Jing, RH and Zhou, DK and Yang, ZY and Ding, ZD and Deng, JH and Xing, Y and Chen, XF},
title = {Does uveitis increase the risk of age-related wet macular degeneration? A Mendelian randomization study.},
journal = {International journal of ophthalmology},
volume = {18},
number = {8},
pages = {1484-1489},
pmid = {40827295},
issn = {2222-3959},
abstract = {AIM: To use two-sample Mendelian randomization (MR) method to study uveitis causal association with wet age-related macular degeneration (wAMD) risk from the genetic level.<br><br>METHODS: Two-sample MR analysis was used to assess the causal role of uveitis on wAMD risk, using the 8 genetic variants associated strongly with uveitis as instrumental variables. Besides, eight MR methods [inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, simple mode, robust adjusted profile score (RAPS), contamination inverse-variance weighted method, and debiased inverse-variance weighted method] were used to get the whole causal estimate for multiple instrumental single nucleotide polymorphism (SNPs). The MR analysis was based on Europeans.<br><br>RESULTS: Uveitis was related to a higher risk of wAMD [odds ratio (OR): 1.08, 95% confidence interval (CI) 1.03-1.12; P=1.03&#xd7;10[-3]] with the IVW method. No heterogeneity and directional pleiotropy were detected. On the contrary, no significant results were detected in reverse MR analysis.<br><br>CONCLUSION: Uveitis is related to an increased risk of wAMD. Due to the high blindness rate of wAMD, understanding and controlling the risk factors of AMD is of great significance for reducing its incidence and early diagnosis and treatment.},
}
@article {pmid40827293,
year = {2025},
author = {Shi, YM and Xie, X and Wang, WQ and Yuan, XM and Zhang, ZP and Wang, HY and Meng, J and Kong, ZH and Jing, X and Liu, TT},
title = {Quantitative characterization of types 1 and 2 macular neovascularization in neovascular age-related macular degeneration with intravitreal conbercept: an analysis utilizing optical coherence tomography angiography.},
journal = {International journal of ophthalmology},
volume = {18},
number = {8},
pages = {1490-1497},
pmid = {40827293},
issn = {2222-3959},
abstract = {AIM: To quantitatively assess central macular thickness (CMT), macular neovascularization (MNV) area, vascular tortuosity (VT), and vascular dispersion (VDisp) in neovascular age-related macular degeneration (nAMD), type 1 and type 2 MNV, by means of optical coherence tomography (OCT) and OCT angiography (OCTA) techniques.<br><br>METHODS: In this retrospective and observational case series, patients were classified into type 1 or type 2 MNV groups. A comprehensive panel of OCT and OCTA metrics was evaluated, including CMT, MNV area, VT, and VDisp. All subjects underwent a standardized intravitreal conbercept (IVC) regimen [3+pro re nata (PRN)] with a 12-month follow-up. MNV area was obtained by manual measurements with OCTA software, and VT and VDisp were calculated by automated analysis with Image J software.<br><br>RESULTS: A total of 101 participants were included, with 51 patients in the type 1 MNV group (mean age 67.32&#xb1;9.12y) and 50 patients in the type 2 MNV group (mean age 64.74&#xb1;5.21y). The mean number of IVC injections was 3.98&#xb1;1.53 for type 1 MNV and 3.73&#xb1;0.81 for type 2 MNV. Both subtypes exhibited significant improvements in visual acuity, accompanied by marked reductions in CMT and MNV area (P<0.05) at 12mo after treatment. In type 2 MNV, VT significantly decreased (P<0.05), whereas no significant change was observed in VT for type 1 MNV. VDisp did not significantly changed in either sybtypes. Moreover, in type 1 MNV, final best-corrected visual acuity (BCVA) using logMAR correlated positively with both pre- and post-treatment CMT, while in type 2 MNV, a significant positive correlation was found between the number of injections and final CMT.<br><br>CONCLUSION: This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area. The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity. The findings imply the quantitative assessment useful for the stratification, prognostication, and personalized management of MNV in nAMD.},
}
@article {pmid40827292,
year = {2025},
author = {Gnanaraj, R and Palestine, AG and Wagner, BD and Patnaik, JL and de Carlo Forest, TE and Mathias, MT and Manoharan, N and Rajeswaren, V and Mandava, N and Lynch, AM},
title = {Systemic C-reactive protein levels in patients with geographic atrophy stratified by sex.},
journal = {International journal of ophthalmology},
volume = {18},
number = {8},
pages = {1498-1505},
pmid = {40827292},
issn = {2222-3959},
abstract = {AIM: To determine the differences in levels of systemic C-reactive protein (CRP) in patients with geographic atrophy (GA) and sex-based differences in CRP levels.<br><br>METHODS: Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration (AMD) registry from August 2014 to June 2021. AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA. High-sensitivity serum CRP levels were measured using an automated nephelometer. A non-parametric (rank-based) linear regression model was fit with an interaction between sex and GA.<br><br>RESULTS: There were 97 GA patients and 139 controls, with females comprising 55% and 66% of each cohort, respectively. There is no difference in CRP between cases and controls, with a median (interquartile range) of 1.2 (0.6-2.6) mg/L in GA patients versus 1.3 (0.8-2.9) mg/L in controls (P=0.52). Although females had higher CRP levels compared to males in both the GA and control groups, this difference did not reach statistical significance after adjustment for multiple comparisons.<br><br>CONCLUSION: There is no significant difference in systemic CRP levels between GA cases and controls.},
}
@article {pmid40823516,
year = {2025},
author = {Mourad, D and Singh, S and Mohamed, F and Zaitoun, A and Al Jayyousi, B},
title = {Prosthetic valve dysfunction post-bevacizumab: a transcatheter aortic valve replacement thrombosis case report.},
journal = {European heart journal. Case reports},
volume = {9},
number = {8},
pages = {ytaf370},
pmid = {40823516},
issn = {2514-2119},
abstract = {BACKGROUND: Transcatheter aortic valve replacement (TAVR) thrombosis is a known complication, but its association with vascular endothelial growth factor (VEGF) inhibitors has not been previously reported.<br><br>CASE SUMMARY: A 69-year-old male with previous TAVR developed new-onset prosthetic valve dysfunction after receiving bevacizumab for age-related macular degeneration. Echocardiography revealed moderate aortic stenosis with significantly elevated gradients compared to baseline. Following discontinuation of bevacizumab and initiation of systemic anticoagulation, valve function normalized at three-month follow-up.<br><br>DISCUSSION: This first reported case of TAVR thrombosis potentially linked to bevacizumab therapy demonstrates a temporal relationship between drug administration and valve dysfunction, with subsequent resolution upon drug discontinuation and anticoagulation. Clinicians should be aware of potential thrombotic complications when prescribing bevacizumab to patients with bioprosthetic valves and maintain regular echocardiographic surveillance. Prompt anticoagulation and medication adjustment may reverse valve dysfunction. Further studies are needed to determine a causal relationship between TAVR thrombosis and VEGF inhibitors.},
}
@article {pmid40822995,
year = {2025},
author = {Khaohoen, A and Chantarasorn, Y},
title = {Clinical Features and Optical Coherence Tomography Angiography in Neovascular Age-Related Macular Degeneration and Pachychoroid Neovasculopathy.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251359847},
pmid = {40822995},
issn = {2474-1272},
abstract = {Purpose: To investigate differences in baseline characteristics, outcomes, and metrics of swept-source optical coherence tomography (SS-OCT) angiography between drusen-associated neovascular age-related macular degeneration (nAMD) vs pachychoroid neovasculopathy. Methods: This prospective cohort study enrolled 1 eye per patient with treatment-naïve nAMD or pachychoroid neovasculopathy who underwent 3 monthly bevacizumab injections followed by a treat-and-extend regimen for 12 months or longer. Eligible patients were classified into 2 groups: those with drusen-associated nAMD and those with pachychoroid neovasculopathy. Drusen-associated nAMD refers to macular neovascularization (MNV) or polypoidal lesions surrounded by subretinal drusenoid deposits or soft drusen 63 μm or larger in diameter. The outcomes were collected at baseline, 6 months, and 12 months. Results: Patients with drusen-bordering MNV (51 cases) were older (69.6 years vs 64.2 years) and had a smaller ratio of low-density to high-density lipoprotein cholesterol (1.85 vs 2.14), longer daily sleep hours (7.03 hours vs 6.07 hours), a smaller proportion of patients with a history of central serous chorioretinopathy (CSCR) (0% vs 12.5%), and smaller baseline central choroidal volume compared with those with pachychoroid neovasculopathy (57 cases). At 12 months, eyes with drusen exhibited a lower choroidal vascularity index, larger foveal thickness (327 µm vs 273 µm), and more antivascular endothelial growth factor injections per year (7.0 vs 5.2) compared with eyes with pachychoroid neovasculopathy. Regarding secondary outcomes, a closed-circuit vascular pattern was associated with persistent retinal fluid at study completion. Conclusions: Patients with pachychoroid neovasculopathy appear to carry some systemic risk factors for CSCR, whereas patients with drusen-related nAMD had inferior responses to bevacizumab monotherapy and greater choriocapillaris hypoperfusion (characterized by thinner choroidal volume and lower choroidal vascularity index values).},
}
@article {pmid40822473,
year = {2025},
author = {Zhang, Y and Chen, Y and Sun, C and Li, F and Shen, Y},
title = {α-Lipoic acid mitigates age-related macular degeneration via ferroptosis: integrative multi-omics and network pharmacology.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1626907},
pmid = {40822473},
issn = {1663-9812},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly. α-Lipoic acid (ALA), a naturally occurring antioxidant and iron-chelator, has shown potential in modulating ferroptosis, but its mechanism in AMD remains unclear.<br><br>METHODS: Network pharmacology, transcriptomic profiling, and machine learning were used to identify potential molecular targets of ALA in AMD. Core genes were identified through interaction network construction, functional enrichment analysis, and machine learning-based screening. Molecular docking and molecular dynamics simulations were performed to assess the binding affinity and stability between ALA and its predicted targets. In vivo validation was conducted using a sodium iodate (SI)-induced AMD mouse model, with retinal structure, function, oxidative stress, and gene expression evaluated through behavioral tests, histological staining, and qRT-PCR.<br><br>RESULTS: We identified six ferroptosis-related core targets (AHCY, DHODH, MAPK1, MAPK8, NOS2, and HMOX1) of ALA implicated in AMD. Molecular docking revealed strong binding affinities between ALA and these six targets, with dynamic simulations confirming stable interactions, particularly with HMOX1 and MAPK1. In the SI-induced AMD mouse model, ALA significantly preserved retinal structure, maintained visual function, and reduced oxidative stress and iron accumulation. qRT-PCR confirmed that ALA exerted differential effects on the expression of the six genes, demonstrating a context-dependent regulatory mechanism.<br><br>CONCLUSION: This study provides multi-level evidence that ALA protects against AMD by modulating ferroptosis-related pathways and restoring retinal structural integrity and functions. These findings warrant further investigation into the therapeutic potential of ALA in AMD.},
}
@article {pmid40821904,
year = {2025},
author = {Yatsu, T and Nagata, A and Chiba, T and Miyata, Y},
title = {Reduction of Heterogeneous nuclear ribonucleoprotein A1 levels in retinal pigment epithelial cells induces inflammation and inhibits autophagy flux: pathology of age-related macular degeneration.},
journal = {Biochemistry and biophysics reports},
volume = {43},
number = {},
pages = {102195},
pmid = {40821904},
issn = {2405-5808},
abstract = {Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) regulates RNA metabolism and inhibits various aging processes. It has also been reported as an inhibitor of inflammation; however, its role in the retina, particularly in retinal pigment epithelial (RPE) cells-a major source of inflammatory cytokines in the retina-remains unclear. Retinal inflammation is a key factor in the development of dry age-related macular degeneration (AMD), an age-related disease that can lead to blindness and currently lacks an established treatment. Therapeutic strategies are focused on preventing the suppression of autophagy, a precursor to inflammation. However, the factors regulating autophagy in RPE cells are not yet fully understood. In this study, we investigated the role of HNRNPA1 in RPE cells to evaluate its potential as a therapeutic target for dry AMD. HNRNPA1 knockdown experiments were conducted, followed by RNA sequencing (RNA-seq) and Gene Ontology term analyses to elucidate the impact of HNRNPA1 reduction. The results revealed that reduced HNRNPA1 levels induced the increased expression of CXCL8 and IL1B, decreased autolysosome formation, and increased autophagosome formation, showing that HNRNPA1 reduction induces inflammation and suppressed autophagy, demonstrating its essential role in maintaining autophagy and mitigating inflammation under normal conditions. Furthermore, in an NaIO3-induced dryAMD model, RPE degeneration was accompanied by a reduction in HNRNPA1. These findings raise the possibility that decreased HNRNPA1 levels play a role in the onset and progression of dry AMD, and support the rationale for further exploring HNRNPA1 as a potential therapeutic target for this currently untreatable condition.},
}
@article {pmid40820958,
year = {2025},
author = {Medina Arellano, AE and Albert-Garay, JS and Huerta, NF and Hernández, KT and Ruiz-Cruz, M and la Paz, LO},
title = {From Neurotransmission to Retinal Pathophysiology: Unraveling the Role of GABA Receptors in Retinal Disease Progression.},
journal = {Journal of neurochemistry},
volume = {169},
number = {8},
pages = {e70198},
pmid = {40820958},
issn = {1471-4159},
support = {PAPIIT IN221023//Direcci&#xf3;n General de Asuntos del Personal Acad&#xe9;mico, Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; CVU 560536//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; CVU 789988//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; CVU 895582//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; CVU 960540//Secretaria de Ciencia, Humanidades, Tecnologia e Inovaci&#xf3;n/ ; LOP.PTR.22-01//Asociaci&#xf3;n para Evitar la Ceguera en M&#xe9;xico I.A.P. Hospital Dr. Luis S&#xe1;nchez Bulnes/ ; },
mesh = {Humans ; *Receptors, GABA/metabolism/physiology ; Animals ; *Synaptic Transmission/physiology ; *Retinal Diseases/physiopathology/metabolism/pathology ; *Retina/metabolism/physiopathology/pathology ; *Disease Progression ; },
abstract = {Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system (CNS). The biological effects of GABA are mediated by activating its receptors, GABAA or GABAB, which are distributed across various tissues, predominantly in the brain and retina. The retina is a neural tissue responsible for receiving and transducing light stimuli. Within this tissue, GABA receptors (GABARs) primarily mediate lateral inhibition in the retina. In recent years, several studies have focused on elucidating the potential role of GABARs in retinal diseases, such as diabetic retinopathy (DR), retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD). This review aims to present the most significant findings from recent years regarding the involvement of GABA receptors in retinal pathologies. Additionally, it highlights the potential of GABA receptors as targets for developing precise therapies or adjunctive strategies for treating retinal diseases.},
}
@article {pmid40820321,
year = {2025},
author = {Song, JR and Park, KH and Kang, SW and Chin, HS and Yu, SY and Park, YH and Kim, YC and Lee, JE and Lim, ST and Kim, JG and Kim, CR and Sagong, M and Oh, HS and Lee, CS and Woo, SJ},
title = {Consensus of Expert Recommendations for the Safe Administration of Brolucizumab in Neovascular Age-related Macular Degeneration.},
journal = {Korean journal of ophthalmology : KJO},
volume = {39},
number = {4},
pages = {362-368},
pmid = {40820321},
issn = {2092-9382},
support = {RS-2023-00248480//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; },
mesh = {Humans ; Angiogenesis Inhibitors/administration &amp; dosage ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; *Consensus ; Intravitreal Injections ; *Practice Guidelines as Topic ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {Brolucizumab offers improved anatomical outcomes and extended dosing intervals compared to aflibercept, reducing treatment burden. However, postmarketing surveillance and real-world studies have highlighted safety concerns, including intraocular inflammation (IOI), retinal vasculitis, and retinal vascular occlusion, necessitating risk management strategies. To address these concerns, a comprehensive review of clinical trials, real-world data, and safety reports were conducted by an expert panel. This consensus report offers practical, evidence-based recommendations to ensure the safe administration of brolucizumab in patients with neovascular age-related macular degeneration (nAMD). The safety management of brolucizumab in patients with nAMD starts with selecting suitable patient profiles through thorough risk assessments. Educating patients about the risk of inflammation and its symptoms is important, as prompt recognition and early medical attention may help improve outcomes. Close monitoring with frequent follow-ups and the use of widefield fundus imaging or peripheral fundus examination are also necessary for early detection and management of complications. Effective management of IOI includes considering discontinuation of brolucizumab, alternative anti-vascular endothelial growth factor therapies, and corticosteroid treatments based on anatomical location and severity of IOI. Differentiating noninfectious IOI from infectious endophthalmitis is essential to ensure appropriate intervention and safeguard vision. In conclusion, this consensus recommendations emphasized the importance of the evidence-based and patient-centered stepwise approaches that should be considered when prescribing brolucizumab to patients with nAMD. This is not an absolute guideline, and the management should be adapted according to the ophthalmic conditions and the patients' opinions after thorough discussions.},
}
@article {pmid40820160,
year = {2025},
author = {Ridley, RB and Tischner, BM and Lee, J and Walsh, E and Massengill, MT and Lewin, AS and Ildefonso, CJ},
title = {Modulation of retinal inflammation delays degeneration in a mouse model of geographic atrophy.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30153},
pmid = {40820160},
issn = {2045-2322},
support = {EY026268//National Eye Institute,United States/ ; S10OD028476/EY/NEI NIH HHS/United States ; M2017126//Bright Focus Foundation/ ; S10 OD028476/OD/NIH HHS/United States ; R01 EY026268/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Disease Models, Animal ; *Geographic Atrophy/pathology/genetics/metabolism ; Dependovirus/genetics ; Transcription Factor RelA/genetics/metabolism/antagonists &amp; inhibitors ; Retina/pathology/metabolism ; *Inflammation/pathology ; Microglia/metabolism ; Oxidative Stress ; Electroretinography ; NF-kappa B/metabolism ; *Retinitis/pathology ; },
abstract = {Geographic atrophy, the advanced form of age-related macular degeneration (AMD), is associated with increased oxidative stress and chronic inflammation. Pro-inflammatory genes, like TNF-α and IL-1β, are under the regulation of the transcription factor p65/RelA. We have previously shown that adeno-associated virus (AAV) delivery of the RelA inhibitory gene M013 blocks retinal inflammation in uveitis models. In this study, we evaluated the effects of RelA inhibition in an oxidative stress-driven geographic atrophy mouse model. We injected Sod2[RPEcKO] mice with rAAV, delivering either secreted GFP (sGFP control) or sGFP fused to a cell-penetrating version of the tagged M013 (sGFP-TatM013v5). Over nine months, we measured retinal function, structure, and morphological changes using electroretinography, optical coherence tomography, and fundoscopy. We quantified changes in inflammatory markers using multiplex ELISA, RT-qPCR, and immunofluorescence staining of the retinal tissue. Finally, we generated an NF-kB-luciferase reporter microglia cell line to study the impact of immune signaling changes on microglia. Mice injected with the rAAV delivering M013 had transient protection of their retinal function at 3 months. Based on ERG evaluations, the intravitreal injection of rAAV delivering sGFP-TatM013v5 significantly delayed the loss of retinal function. Furthermore, the rAAV-mediated expression of the sGFP-TatM013v5 protected photoreceptors' outer and inner segments based on OCT and immunofluorescence analysis. Analysis of postmortem tissues showed decreased migration of immune cells towards the RPE. Retinas injected with the sGFP-M013v5 vector showed increased levels of IL-9, IL10 and LIF. Finally, adding LIF to our NF-kB reporter cell line showed decreased TNF-induced reporter expression and modulation of microglia-specific genes. Our results indicate that modulating retinal inflammation could significantly slow the degeneration associated with geographic atrophy. Specifically, inhibiting the RelA protein in the retina may offer protective effects against retinal degeneration. Additionally, we demonstrated that LIF can counteract the influence of TNF on microglial gene expression. Future research will explore the dynamic interactions between RelA and other transcription factors and the NF-kB signaling pathway in the retina as they relate to retinal diseases.},
}
@article {pmid40820046,
year = {2025},
author = {Boscia, G and Chauhan, D and Corradetti, G and O'Neill, CP and Samarasinghe, G and Lindenberg, SM and Urrea, A and Mauger, S and Do, G and Gupta, M and Sadda, SR},
title = {The impact of swithching faricimab in the treatment of neovascular age-related macular degeneration: a real-world analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {11},
pages = {3097-3103},
pmid = {40820046},
issn = {1435-702X},
}
@article {pmid40819748,
year = {2025},
author = {Shang, Z and Qin, D and Liu, X and Li, H and Liu, C and Zhang, R and Sun, T and Pan, Z and Feng, W and You, X},
title = {The cGAS-STING pathway in age-related ocular diseases: Mechanisms and therapeutic opportunities.},
journal = {Cellular signalling},
volume = {135},
number = {},
pages = {112069},
doi = {10.1016/j.cellsig.2025.112069},
pmid = {40819748},
issn = {1873-3913},
mesh = {Humans ; *Nucleotidyltransferases/metabolism ; *Membrane Proteins/metabolism ; *Signal Transduction ; *Aging/metabolism ; Animals ; *Macular Degeneration/metabolism/pathology ; *Eye Diseases/metabolism/pathology ; Cellular Senescence ; },
abstract = {The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial component of the innate immune system, which senses abnormal double-stranded DNA in the cytoplasm and induces the type I interferon and pro-inflammatory cytokines expression. In cellular senescence, the cGAS-STING signaling pathway triggers the senescence-associated secretory phenotype, thereby exacerbating the senescence phenomenon and leading to age-related ocular diseases, including age-related macular degeneration and diabetic retinopathy. Herein, we outline the structure of cGAS-STING signaling pathway and its association with cellular senescence, and discuss the mechanism of behavior between cGAS-STING and ocular aging-related diseases. Finally, we summarize the relevant inhibitors of the cGAS-STING signaling pathway, thereby offering a novel direction for exploring the mechanism of ocular aging-related inflammatory diseases.},
}
@article {pmid40819142,
year = {2025},
author = {Anjum, F and Maqbool, F and Razzaq, MS and Shehzad, HMF and Ali, S and Shah, D and Tahir, M and Ilyas, M},
title = {Semantic web ontology for structured knowledge representation and clinical decision support in eye diseases.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {29986},
pmid = {40819142},
issn = {2045-2322},
mesh = {Humans ; *Eye Diseases/diagnosis/therapy ; *Semantic Web ; *Biological Ontologies ; *Decision Support Systems, Clinical ; },
abstract = {Vision is a vital sense that allows people to interact with their surroundings and carry out tasks efficiently while maintaining safety and independence. At least 2.2 billion people globally suffer from blindness or vision impairment, of which more than 1 billion cases are avoidable or untreated because they lack access to eye care services. In ophthalmology, there are numerous challenges in knowledge organization and management, mainly due to the complexity of eye diseases. Ontologies are used as excellent tools for organizing and managing complicated information due to their structured representations of domain knowledge and to make data more findable, accessible, interoperable, and reusable. We have developed an ontology, that is, Eye Disease Ontology (EDO), for the most common eye diseases as a resource that helps in data extraction and analysis for the general public and medical professionals. EDO is a comprehensive and systematic knowledge representation system that categorizes and organizes information about commonly occurring eye diseases such as cataracts, glaucoma, age-related macular degeneration, etc, and connects it to vital details such as symptoms, causes, risk factors, diagnostic tests, and treatment options. The significant metrics of EDO include 566 classes, 16 object properties, 12 data properties, and 119 instances. In this study, the ontology of eye diseases has the potential to improve clinical diagnosis, advance research, and enrich medical education, while improving patient care. This ontology was created using the NeOn technique in the Protégé/OWL environment. Several competency questions were created to meet the demands of various stakeholders, and the ontology was validated using SPARQL queries, the Hermit Reasoner, and the OOPS Pitfalls Scanner. In addition, we develop comprehensive documentation for EDO to promote reuse and emphasise the importance of reuse in future applications.},
}
@article {pmid40818729,
year = {2025},
author = {Rajeswaren, V and Trivedi, V and Yoganathan, P},
title = {Macular hole after anti-Vascular Endothelial Growth factor injection: A review.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.08.009},
pmid = {40818729},
issn = {1879-3304},
abstract = {Anti-vascular endothelial growth factor (VEGF) injections are a crucial treatment for neovascular age-related macular degeneration (nvAMD). However, each injection carries the risk of complications, including macular hole (MH) formation. A comprehensive literature search of the PubMed, Embase, and Google Scholar databases identified studies reporting MH formation after anti-VEGF injections for nvAMD. Demographic characteristics included age, sex and affected eye. The presence of intraretinal fluid, subretinal fluid (SRF), pigment epithelial detachment (PED), posterior vitreous detachment, epiretinal membrane, vitreomacular adhesion (VMA), vitreomacular traction (VMT), and retinal pigment epithelial (RPE) tears was recorded. This review includes 15 articles, encompassing 50 eyes. Median patient age was 76.0 years, and 54% were female. Prior to MH formation, SRF and PED were present in 68% of eyes. VMA or VMT was observed in 36% of eyes and the median number of injections before MH development was 3, with a median time to diagnosis of 60 days. While anti-VEGF is an essential therapy, clinicians must be aware of the risk of MH. Predisposing factors including PEDs, VMT, and significant intra- or subretinal fluid, should be considered. Further research is needed to fully understand the mechanisms and explore preventative strategies.},
}
@article {pmid40817925,
year = {2025},
author = {Sacconi, R and Menna, M and Marra, S and Beretta, F and Bandello, F and Querques, G},
title = {Subthreshold laser treatment does not change choriocapillaris perfusion in patients with intermediate age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {11},
pages = {3091-3096},
doi = {10.1007/s00417-025-06926-2},
pmid = {40817925},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; Fluorescein Angiography/methods ; Male ; Female ; Aged ; Fundus Oculi ; Follow-Up Studies ; *Visual Acuity ; Regional Blood Flow/physiology ; *Laser Coagulation/methods ; Capillaries/diagnostic imaging ; Aged, 80 and over ; *Macular Degeneration/surgery/diagnosis/physiopathology ; Middle Aged ; Treatment Outcome ; Prospective Studies ; *Retinal Vessels/physiopathology/diagnostic imaging ; },
abstract = {PURPOSE: To evaluate the safety of subthreshold laser treatment (SLT) at the level of the choriocapillaris (CC) using optical coherence tomography angiography (OCTA) in patients affected by intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This is an analysis of patients included in the PASCAL clinical trial, including iAMD patients with reticular pseudodrusen (RPD). OCTA imaging was performed at baseline, 1-month, and 3-month follow-ups, focusing on a 3&#x2009;&#xd7;&#x2009;3-mm treated area. The CC slab was segmented and analyzed quantitatively for flow voids using the Phansalkar binarization method. Flow voids in the treated area were compared to no-treated areas and analyzed across time points.<br><br>RESULTS: 20 patients (20 eyes) were included in the study. No significant differences in CC flow voids (%) were observed between treated and no-treated areas at baseline (27.9% vs. 24.6%, p&#x2009;=&#x2009;0.641), nor were significant changes noted over time in treated areas (baseline: 27.9%, 1-month: 28.8%, 3-month: 32.6%, p&#x2009;=&#x2009;0.115). Similarly, no-treated areas exhibited no significant alterations over time (baseline: 24.1%, 1-month: 24.3%, 3-month: 26.8%, p&#x2009;=&#x2009;0.204).<br><br>CONCLUSION: SLT did not induce detectable CC damage or alter perfusion in treated areas, further confirming its safety in managing RPD secondary to dry AMD. These findings support SLT as a viable therapeutic option, warranting further investigation to validate its long-term efficacy and safety.},
}
@article {pmid40817252,
year = {2025},
author = {Schroers, A and Neueder, A and Massoudy, I and Dillinger, AE and Ergün, S and Braunger, BM and Schlecht, A},
title = {Illuminating photoreceptors: TGFβ signaling modulates the severeness of retinal degeneration.},
journal = {Cell death discovery},
volume = {11},
number = {1},
pages = {384},
pmid = {40817252},
issn = {2058-7716},
support = {SCHL2362-2//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; NE 2372/1-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BR 4957/3-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BR 4957/4-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
abstract = {In various ocular diseases, retinal degeneration (RD) is a clinical symptom that can lead to irreversible vision loss. These diseases include age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Retinal degeneration describes a process during which the retina deteriorates due to the gradual death of photoreceptor cells. Although extensive research has been pursued to identify the underlying pathomechanisms, the precise molecular mechanisms that leads to photoreceptor death remains unclear. In this study, we combined the mouse model of light-induced photoreceptor degeneration with single-cell RNA sequencing to decipher the transcriptional response of degenerating photoreceptor cells. We additionally performed pseudotime analysis of gene expression changes for both the control and light-damaged photoreceptor clusters to analyze the extent of degeneration following a virtual trajectory of severeness. We found a transcriptional heterogeneity of rod photoreceptors in both control and degenerative conditions, and mapped several rod clusters which strongly differ in their transcriptional profile. We defined one of these clusters as the predominant disease-associated rod cluster, containing the most severely damaged rod cells. Pseudotime analysis demonstrated a strong regulation of TGFβ signaling and the RNA-induced silencing complex (RISC) in light-damaged photoreceptors suggesting a pivotal role of these mediators in retinal degeneration.},
}
@article {pmid40816663,
year = {2025},
author = {Soylu, C and Corradetti, G and Alhelaly, M and Khan, H and Aziz, AA and Khan, H and Ali, H and Sulahria, H and Khanani, AM and Sadda, S},
title = {Real-World Outcomes in Eyes With Neovascular AMD Switched From Brolucizumab to Faricimab: A TRUCKEE Study Analysis.},
journal = {American journal of ophthalmology},
volume = {280},
number = {},
pages = {169-175},
doi = {10.1016/j.ajo.2025.08.018},
pmid = {40816663},
issn = {1879-1891},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity/physiology ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Treatment Outcome ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Drug Substitution ; Follow-Up Studies ; Fluorescein Angiography ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {OBJECTIVE: To investigate anatomical and functional outcomes in a subset of eyes with neovascular age-related macular degeneration (nAMD) switched from brolucizumab to faricimab in the real-world TRUCKEE study.<br><br>DESIGN: Retrospective, multicentric clinical cohort study.<br><br>SUBJECTS AND PARTICIPANTS: 134 eyes of 108 patients were switched from brolucizumab to faricimab. This study included 56 eyes (49 patients) with complete data after 1 injection of faricimab and 40 eyes (34 patients) with complete data after 3 injections of faricimab.<br><br>METHODS: A multicenter, retrospective chart review was conducted on real-world participants enrolled in the TRUCKEE study switched from brolucizumab to faricimab for the treatment of nAMD. Participants were considered eligible for this post-hoc analysis if they had documented anatomical and functional outcome data following 1 and 3 injections of faricimab after being switched from brolucizumab. A comparative analysis was performed using the Wilcoxon signed-rank test.<br><br>MAIN OUTCOME MEASURES: Change in best corrected visual acuity (BCVA) measured in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, durability - defined as time interval between treatments in days, and central subfield thickness (CST), following 1 and 3 injections of faricimab.<br><br>RESULTS: The mean age of patients who had complete data after 1 injection of faricimab was 81.1 &#xb1; 7.1 years, and 25 were males. After 1 injection of faricimab following the switch, (mean treatment interval of 57.0 &#xb1; 32.9 days) a significant reduction in CST was observed (mean -5.25 &#xb5;m, P = .048). Changes in BCVA and durability were not statistically significant after 1 injection. The mean age of patients who had data after 3 injections was 80.4&#xb1;7.7 years, and 16 were males. The mean CST reduction measured -11.28 &#xb5;m, when comparing post-faricimab with post-brolucizumab values (P = .086). Additionally, after 3 injections of faricimab, a numerical increase in retreatment interval (+5.0 days, P = .769) and improvement in visual acuity (BCVA +1.63 letters, P = .174) were observed, though these were not statistically significant.<br><br>CONCLUSIONS: Switching from brolucizumab to faricimab was associated with numerical improvements in BCVA, CST, and retreatment interval. The apparent benefit in patients already on maximum VEGF suppression with brolucizumab, may suggest the relevance of angiopoetin-2 suppression with faricimab.},
}
@article {pmid40816649,
year = {2025},
author = {Lugassy, Y and Berent, E and Tarony, L and Jeries, S and Ziv, T and Savion, N and Eldar-Finkelman, H},
title = {HDAC inhibition protects RPE cells from oxidative stress via enhanced mitochondrial fusion, cytoskeletal repair, and Nrf-2 activation.},
journal = {Free radical biology &amp; medicine},
volume = {240},
number = {},
pages = {59-70},
doi = {10.1016/j.freeradbiomed.2025.08.007},
pmid = {40816649},
issn = {1873-4596},
mesh = {*Oxidative Stress/drug effects ; *Histone Deacetylase Inhibitors/pharmacology ; Humans ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology/cytology ; Hydroxamic Acids/pharmacology ; *Mitochondrial Dynamics/drug effects ; Vorinostat/pharmacology ; *NF-E2-Related Factor 2/metabolism/genetics ; Rotenone/pharmacology/toxicity ; Reactive Oxygen Species/metabolism ; Cytoskeleton/drug effects/metabolism ; Mitochondria/drug effects/metabolism ; *Macular Degeneration/drug therapy/pathology/metabolism/genetics ; Histone Deacetylase 6/antagonists &amp; inhibitors/genetics ; Kelch-Like ECH-Associated Protein 1/genetics/metabolism ; Cell Line ; Cell Survival/drug effects ; Heme Oxygenase-1/genetics/metabolism ; },
abstract = {Oxidative stress is a key driver of retinal pigment epithelium (RPE) damage and the development of age-related macular degeneration (AMD). Here, we demonstrate that the histone deacetylase (HDAC) inhibitors vorinostat and trichostatin A (TSA) elicit a coordinated cytoprotective response in RPE cells exposed to rotenone. Both compounds significantly reduced reactive oxygen species (ROS) levels, enhanced mitochondrial fusion, increased mitochondrial ATP production, and improved cell morphology and cell survival in the rotenone-treated cells. In addition, the compounds activated Nrf-2 as evidenced by Keap1 downregulation, increased p62/SQSTM1 expression, and induction of Nrf-2 targets, including heme oxygenase 1 (HO-1). Proteomic analysis of drug-treated cells revealed a significant enrichment of proteins involved in cytoskeletal organization and dynamics. Consistently, specific staining for actin filaments confirmed that vorinostat and TSA preserved cytoskeletal architecture and increased levels of the tight junction protein TJP3 in cells exposed to rotenone. Finally, inhibition of the vorinostat/TSA target HDAC6, or blockade of α-tubulin acetyltransferase, demonstrated that modulation of α-tubulin acetylation could influence ROS levels. Similarly, enhanced mitochondrial fusion by Mdivi-1 reduced ROS accumulation in the rotenone-treated cells. However, these last two interventions did not fully recapitulate the antioxidant effects observed with vorinostat or TSA. Our results identify a multifaceted protective mechanism triggered by HDAC inhibition in oxidatively stressed RPE cells and support the therapeutic repurposing of vorinostat in oxidative stress-driven RPE or retinal degeneration.},
}
@article {pmid40815370,
year = {2025},
author = {Li, C and Chen, M and Lu, Y},
title = {An assessment of anti-VEGF drugs safety based on real-world data: from popularity to spontaneous reporting in eudravigilance database.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {11},
pages = {3257-3270},
pmid = {40815370},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Databases, Factual ; Aged ; Ranibizumab/adverse effects/administration &amp; dosage ; Intravitreal Injections ; *Adverse Drug Reaction Reporting Systems/statistics &amp; numerical data ; *Wet Macular Degeneration/drug therapy ; Aged, 80 and over ; Middle Aged ; *Pharmacovigilance ; Incidence ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins/adverse effects ; Bevacizumab/adverse effects/administration &amp; dosage ; *Drug-Related Side Effects and Adverse Reactions/epidemiology ; },
abstract = {PURPOSE: Anti-vascular endothelial growth factor (VEGF) drugs are the first-line treatment for neovascular age-related macular degeneration (nAMD). This study analyzed four commonly used anti-VEGF drugs, preliminarily compared the search query results for these drugs on Google to assess public interest and analyzed the profile of ocular adverse drug reactions (ADRs) for these drugs in the EudraVigilance (EV) database.<br><br>METHODS: A descriptive retrospective study was conducted. We observed four commonly used anti-VEGF drugs for the clinical treatment of nAMD, with ADR reports sourced from the EV database. Data collected included age, gender, regional distribution, and report origins. We analyzed the overall characteristics of these ADR reports and explored the distribution across 27 System Organ Classes (SOCs) for these drugs. Additionally, we compared the off-label use ratios and severe outcomes of these drugs. Subsequently, we used disproportionality analysis (DPA) to compare the relationship between these drugs and ocular ADRs. Lastly, we compared the most common ocular ADRs among different drugs and the similarities and differences in ocular ADRs.<br><br>RESULTS: Google Trends indicated that in 2024, the interest scores for the four drugs ranked from highest to lowest were aflibercept, ranibizumab, faricimab, and brolucizumab. As of October 22, 2024, the total number of Individual Case Safety Reports (ICSRs) for the four drugs uploaded in EV was 32,878, with a higher proportion of ADR reported in brolucizumab-treated cases compared to the other three drugs. The age group of 65-85 years reported the highest incidence, and a higher proportion of ADRs occurred in females. Compared to the European Economic Area (EEA), more cases were reported for these drugs in NON-EEA regions, with reports primarily from healthcare professional (HP). Eye disorders were the most frequently reported among the four drugs. The frequency of ADRs reported for off-label use was highest with faricimab, while ranibizumab had a higher number of cases with severe outcomes. DPA revealed that brolucizumab had a significantly higher reporting rate of ocular ADRs compared to the other three inhibitors.<br><br>CONCLUSION: Anti-VEGF drugs often cause ocular ADRs when treating nAMD, which should be a clinical concern. To reduce the risk of adverse reactions, clinicians should closely monitor patients using these drugs.},
}
@article {pmid40814782,
year = {2025},
author = {Bond, K and Klokman, G and Xu, Y and Wu, X and Schustak, J and Mandelbaum, J and Twarog, M and Han, H and Aihara, F and Paulina, MK and Coble, M and Hayden, C and Galarneau, JR and Demirs, JT and Qiu, Y and Esterberg, R and Huang, Q and Prasanna, G and Wilson, CW and Saint-Geniez, M and Aranda, J and Bao, Y},
title = {Double-Stranded RNA Induces Retinal Pigment Epithelium Cell Degeneration and Inflammation.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {16},
pages = {e70786},
doi = {10.1096/fj.202402181R},
pmid = {40814782},
issn = {1530-6860},
support = {//Novartis (Novartis AG)/ ; },
mesh = {*Retinal Pigment Epithelium/pathology/metabolism ; *RNA, Double-Stranded/genetics/metabolism ; Animals ; Humans ; Mice ; *Inflammation/metabolism/pathology/genetics ; *Macular Degeneration/pathology/metabolism/genetics ; Mice, Inbred C57BL ; DEAD Box Protein 58/metabolism/genetics ; Signal Transduction ; Geographic Atrophy/metabolism/pathology ; Receptors, Immunologic ; },
abstract = {RIG-I signaling has been previously implicated as a driver of inflammation to the retinal pigment epithelium (RPE) during age-related macular degeneration (AMD). Double-stranded RNA (dsRNA) is known to initiate RIG-I signaling and lead to a type I interferon response. We show through shRNA knockdown that RIG-I is essential for initiating an interferon response in iPS-RPE in response to both synthetic dsRNA-mimetic 3p-hpRNA and the double-stranded retrotransposable element Alu. Analysis of human tissue from patients suffering from AMD show accumulation of dsRNA, peaking at the geographic atrophy (GA) stage. Using a new murine model of 3p-hpRNA subretinal challenge to RPE cells, we confirmed that accumulation of dsRNA initiates a type I interferon response, as well as RPE and photoreceptor degeneration. Although RPE response to synthetic dsRNA was acute, extensive leukocyte migration was observed. The results from this study verify the importance of RIG-I signaling in regulating inflammation in the subretinal space and implicates dsRNA accumulation as a driver of AMD pathogenesis.},
}
@article {pmid40814089,
year = {2025},
author = {Plasencia, C and Eschle, J and Hatz, K},
title = {Management and safety of same day bilateral intravitreal anti-VEGF injections in a treat-and-extend regimen.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {459},
pmid = {40814089},
issn = {1471-2415},
mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; *Ranibizumab/administration &amp; dosage ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Visual Acuity ; *Macular Edema/drug therapy ; Middle Aged ; Retinal Vein Occlusion/drug therapy ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (VEGF) intravitreal injection treatment (IVT)s are gold standard for various neovascular retinal diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema due to retinal vein occlusion (RVO). Same day bilateral IVTs are commonly performed off-label worldwide to reduce patient burden, despite limited safety data. This study evaluates the safety and management of bilateral same day anti-VEGF injections within a treat-and-extend regimen (TER) and proposes a clinical guideline for coordination of bilateral treatment.<br><br>METHODS: This retrospective observational study analysed electronic health records of 428 included patients treated bilaterally with ranibizumab 0.5mg or aflibercept 2mg at the VISTA Augenklinik (Binningen, Switzerland) between 2015 and 2019. Patients included had bilateral macular edema due to nAMD, DME, or RVO and received at least two cycles of same day bilateral anti-VEGF injections within the TER. Treatment coordination followed one of four strategies: Equal TER, Coordinated TER, Mixed TER and pro re nata (PRN), and Asynchronous TER. Unilateral IVTs were also recorded during the same period in the same patient cohort. Ocular and systemic adverse events (AEs) were compared between unilateral and bilateral injections using Fisher's exact test.<br><br>RESULTS: A total of 15,825 anti-VEGF injections were administered: 4,766 bilateral same day injections ([Formula: see text]) and 6,293 unilateral injections. Treatment intervals were synchronised according to visual acuity potential and disease activity. A treatment regime for bilateral IVTs has been established and is provided in the manuscript. The most frequently reported ocular AEs were conjunctival haemorrhage and sicca symptoms. Systemic AEs such as cerebrovascular and cardiovascular events were rare, with no significant difference between bilateral and unilateral injections.<br><br>CONCLUSION: Bilateral same day intravitreal anti-VEGF injections within a TER regimen appear to be safe with no significant increase in ocular or systemic AEs compared to unilateral treatment. Coordinating bilateral IVTs using the clinical guideline presented in this study may reduce treatment visits, ease patient burden and improve compliance. Larger prospective studies are needed to confirm safety and support standardised guidelines for bilateral IVTs.},
}
@article {pmid40813679,
year = {2025},
author = {Gao, S and Guo, D and Huang, P and Yin, N and Jia, H and Li, S and Sun, X and Zhu, X},
title = {Molecular marker discovery and detection for blinding eye disease.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {565},
pmid = {40813679},
issn = {1477-3155},
mesh = {Humans ; *Biomarkers/analysis/metabolism ; Aqueous Humor/chemistry/metabolism ; Female ; Male ; *Chemokine CCL2/analysis/metabolism ; Aged ; Middle Aged ; Proteomics/methods ; *Macular Degeneration/diagnosis/metabolism ; Reproducibility of Results ; Adult ; Cataract/diagnosis/metabolism ; },
abstract = {Accurate, sensitive, and specific detection of molecular markers in intraocular fluid will facilitate the early discovery, diagnosis, and intervention of eye diseases. In this study, a total of 168 participants were recruited and divided into two distinct cohorts: discovery and verification. In the discovery phase, proteomic analysis identified MCP-1 in aqueous humor as a potential molecular marker for blinding eye disease. We further developed a molecular detection technology for the marker based on biolayer interference sensing. The technology utilizes a sandwich strategy with one-to-one pairing of two different biorecognition molecules for MCP-1. It also incorporates automation, high throughput, and real-time monitoring, achieving highly selective recognition and accurate analysis of MCP-1. It demonstrates a low detection limit (0.16 pM), good reliability (R[2] = 0.995), and a wide analytical range (0.244-1000 pM) for MCP-1 in human aqueous humor samples. Crucially, in the verification phase with 150 subjects, the technology achieved a high detection rate (95.0%) for patients with age-related macular degeneration and high myopia cataract in under 30 min, and was able to further differentiate between them with a specificity of 86.0%. Therefore, the developed molecular detection technology may provide a robust, convenient, and valuable solution for widespread screening, early discovery, and differential diagnosis of blinding eye diseases.},
}
@article {pmid40813365,
year = {2025},
author = {Schubert, A and Lobo Barbosa da Silva, ME and Ambrock, T and Terosian, O and Malyshkina, A and Padberg, C and Larafa, S and Matschke, J and Fandrey, J and Henning, Y},
title = {Targeting hypoxia-inducible factor-1 in a hypoxidative stress model protects retinal pigment epithelium cells from cell death and metabolic dysregulation.},
journal = {Cell death discovery},
volume = {11},
number = {1},
pages = {380},
pmid = {40813365},
issn = {2058-7716},
abstract = {Oxidative stress and hypoxia lead to dysfunction of retinal pigment epithelium (RPE) cells and are hallmarks of diseases such as age-related macular degeneration (AMD), the most common blinding disease in the elderly population. We have previously shown that a combination of these two risk factors, i.e. hypoxidative stress, exacerbates RPE cell death by ferroptosis. Hypoxia leads to stabilization of hypoxia-inducible factors (HIFs), key regulators of cellular adaptation to hypoxic conditions. In the present study, we have therefore investigated the roles of HIF-1 and HIF-2 in RPE cell death in a human RPE cell line under hypoxidative stress. For this purpose, we conducted siRNA-mediated knockdowns of the α-subunits of HIF-1 and HIF-2. We found that especially iron metabolism, in particular the expression of transferrin receptor 1 (TFR1) was affected by HIF-1α silencing, resulting in decreased intracellular iron levels and ferroptosis susceptibility. We also found that heme oxygenase 1 (HO-1) contributed to cell death by hypoxidative stress. In addition, we also observed that cell metabolism was improved by HIF-1α silencing under hypoxia, most likely contributing to the protective effect. Furthermore, we identified an FDA-approved small molecule inhibitor, Vorinostat, to downregulate HIF-1α, TFR1, and HO-1 and improve cell metabolism, which eventually resulted in a full rescue of RPE cells from hypoxidative stress-induced cell death. In conclusion, this study highlights the importance of considering targeted HIF inhibition as a promising approach to protect RPE cells from degeneration.},
}
@article {pmid40812795,
year = {2025},
author = {Pu, J and Zhuang, X and Li, M and Zhang, X and Ji, Y and Mi, L and Hao, X and He, G and Su, Y and Gan, Y and Zhang, Y and Chen, X and Wen, F},
title = {Association between early lesion response and long-term anti-VEGF injection frequency in nAMD: a 2-year prospective study using 3D volumetric analysis.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327339},
pmid = {40812795},
issn = {1468-2079},
abstract = {PURPOSE: To explore the association between early response of different lesions and the number of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study included treatment-na&#xef;ve nAMD eyes with a 2-year follow-up period. Volumetric changes of multiple lesions during the loading phase were documented, including subretinal fluid (SRF), intraretinal fluid (IRF), vascular subretinal hyper-reflective material (vSHRM) and avascular subretinal hyper-reflective material, fibrovascular pigment epithelial detachment and serous pigment epithelial detachment (sPED) and total lesion. Imaging biomarkers associated with treatment frequency were analysed for 1-year and 2-year periods.<br><br>RESULTS: A total of 92 eyes (92 patients) were included, with a mean age of 65.77&#xb1;7.28 years. During the loading phase, all lesions except vSHRM showed significant temporal changes (p<0.05). Multivariate regression revealed that greater SRF changes at month 3 and IRF changes at month 1 were associated with increased injection frequency for both 1-year (&#x3b2;=0.353&#x2009;and 0.360, p=0.025&#x2009;and 0.022) and 2-year periods (&#x3b2;=0.336&#x2009;and 0.293, p=0.004&#x2009;and 0.026). Conversely, greater changes in vSHRM and sPED at month 2 were associated with fewer first-year injections (&#x3b2;=-0.307&#x2009;and -0.697, p=0.023&#x2009;and 0.022), while sPED changes at months 2 and 3 correlated with reduced 2-year requirements (&#x3b2;=-0.845&#x2009;and -0.297, p=0.005&#x2009;and 0.031).<br><br>CONCLUSION: Enhanced absorption of SRF and IRF during early treatment was associated with increased injection frequency, while greater absorption of vSHRM and sPED correlated with reduced treatment requirements.<br><br>TRIAL REGISTRATION NUMBER: ChiCTR2200063428.},
}
@article {pmid40812794,
year = {2025},
author = {Dong, L and Gao, W and Niu, L and Deng, Z and Gong, Z and Li, HY and Fang, LJ and Shao, L and Zhang, RH and Zhou, WD and Ma, L and Wei, WB},
title = {AI-based prediction of best-corrected visual acuity in patients with multiple retinal diseases using multimodal medical imaging.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327189},
pmid = {40812794},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: This study evaluated the performance of artificial intelligence (AI) algorithms in predicting best-corrected visual acuity (BCVA) for patients with multiple retinal diseases, using multimodal medical imaging including macular optical coherence tomography (OCT), optic disc OCT and fundus images. The goal was to enhance clinical BCVA evaluation efficiency and precision.<br><br>METHODS: A retrospective study used data from 2545 patients (4028 eyes) for training, 896 (1006 eyes) for testing and 196 (200 eyes) for internal validation, with an external prospective dataset of 741 patients (1381 eyes). Single-modality analyses employed different backbone networks and feature fusion methods, while multimodal fusion combined modalities using average aggregation, concatenation/reduction and maximum feature selection. Predictive accuracy was measured by mean absolute error (MAE), root mean squared error (RMSE) and R&#xb2; score.<br><br>RESULTS: Macular OCT achieved better single-modality prediction than optic disc OCT, with MAE of 3.851 vs 4.977 and RMSE of 7.844 vs 10.026. Fundus images showed an MAE of 3.795 and RMSE of 7.954. Multimodal fusion significantly improved accuracy, with the best results using average aggregation, achieving an MAE of 2.865, RMSE of 6.229 and R&#xb2; of 0.935. External validation yielded an MAE of 8.38 and RMSE of 10.62.<br><br>CONCLUSION: Multimodal fusion provided the most accurate BCVA predictions, demonstrating AI's potential to improve clinical evaluation. However, challenges remain regarding disease diversity and applicability in resource-limited settings.},
}
@article {pmid40811806,
year = {2025},
author = {Arrigo, A and Aragona, E and Antropoli, A and Bianco, L and Saladino, A and Fabbro, SD and Bandello, F and Parodi, MB},
title = {Age-related retinal pigment epithelium disease (ARPED): clinical and differential features.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004644},
pmid = {40811806},
issn = {1539-2864},
abstract = {PURPOSE: We described the clinical characteristics of age-related retinal pigment epithelium disease (ARPED). This looks like an age-related, retinal disease showing a primary retinal pigment epithelium (RPE) involvement, no typical age-related macular degeneration (AMD) features, and no pachychoroid-related characteristics.<br><br>METHODS: The study was designed as observational, both cross-sectional and retrospective investigation. We collected data from patients affected by ARPED, defined by precise diagnostic criteria. We performed both qualitative and quantitative multimodal retinal imaging investigations. The main outcome measure is the characterization of ARPED, defined by precise diagnostic criteria, with respect to AMD. Secondary outcome is the identification of differential diagnostic features with respect to other retinal diseases.<br><br>RESULTS: We included 31 ARPED eyes (62 patients). Inter-graders agreement for detecting ARPED was 0.98 (p<0.05). ARPED is characterized by the absence of AMD-related findings, such as drusen and pseudodrusen. Moreover, it is characterized by the absence of pachychoroid-related features, as also confirmed by fluorescein angiography and indocyanine green angiography.<br><br>CONCLUSIONS: Although further studies are warranted to better define ARPED features and if it may be considered a distinct macular disease, the characteristics of this clinical phenotype introduce new intriguing pathophysiologic features and should be carefully considered both in clinical practice and research contexts.},
}
@article {pmid40810576,
year = {2025},
author = {Miao, H and Qu, T and Huang, Y and Fan, S and Yang, Y and Lv, A and Hu, J and Guo, L and Jia, Q and Li, Z and Zhang, S and Li, Y and Shi, W and Chen, Y and Chen, S and Yan, H},
title = {The Impact of Helicobacter pylori Infection on Retinal Nerve Fiber Layer and Macula.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {35},
pmid = {40810576},
issn = {1552-5783},
mesh = {Humans ; *Helicobacter Infections/complications/diagnosis/microbiology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; *Helicobacter pylori/isolation &amp; purification ; Tomography, Optical Coherence/methods ; *Nerve Fibers/pathology ; *Retinal Ganglion Cells/pathology ; *Macula Lutea/pathology ; Aged ; Adult ; *Eye Infections, Bacterial/microbiology/diagnosis ; *Macular Degeneration/diagnosis/epidemiology ; Incidence ; },
abstract = {PURPOSE: This study aims to elucidate the effects of Helicobacter pylori infection on the retinal nerve fiber layer (RNFL) and macula.<br><br>METHODS: A cross-sectional study was undertaken at the Health Examination Center of the First Hospital of Handan from 2021 to 2022. Participants who underwent both the 14C-urea breath test and ocular examinations were selected. The RNFL and macula were assessed using a swept-source optical coherence tomography device (Topcon OCT, Tokyo, Japan). Data are presented as mean &#xb1; SD and were analyzed using the Mann-Whitney U-test and t-test, with a significance level set at P < 0.05.<br><br>RESULTS: RNFL analysis of 1693 H. pylori-positive and 1693 negative left eyes revealed significantly thinner inferior temporal RNFL in the H. pylori-positive group (149.79 &#xb1; 29.55&#xa0;&#xb5;m vs. 152.76 &#xb1; 29.15&#xa0;&#xb5;m, P = 0.026). No other regional RNFL differences were found (P > 0.05). In the macula study of 2117 H. pylori-positive and 2117 negative participants, macular degeneration occurred in 74 positive (avgerage age 54.66 &#xb1; 10.08 years) and 67 negative individuals (avgerage age 60.22 &#xb1; 10.50 years). The incidence rates were not significantly different (P > 0.05), but the positive group with lesions was significantly younger (P = 0.002).<br><br>CONCLUSIONS: H. pylori infection may be associated with localized defects in the RNFL, which could serve as early indicators of glaucoma, and it may also be potentially linked to accelerated progression of macular degeneration.},
}
@article {pmid40809969,
year = {2025},
author = {Liu, Z and Hammer, DX},
title = {Wide-field choriocapillaris mapping with 3.4 MHz adaptive optics-optical coherence tomography angiography.},
journal = {Biomedical optics express},
volume = {16},
number = {8},
pages = {3255-3269},
pmid = {40809969},
issn = {2156-7085},
abstract = {The human choriocapillaris (CC) plays an essential role in supporting the overlying photoreceptor and retinal pigment epithelial cells and in maintaining overall retinal health. Disruption of CC structure and function is implicated in many retinal diseases, including age-related macular degeneration. Despite recent advances in ophthalmic imaging technologies, a full understanding of disease mechanisms remains elusive due to the inability to visualize CC microstructure. Here, we present a 3.4 MHz adaptive optics-optical coherence tomography angiography (AO-OCTA) approach for mapping the human choriocapillaris at high resolution to address the primary limitations of existing methodologies for CC imaging. We optimized our AO-OCTA acquisition protocols and offered guidelines for performing AO-OCTA for vessel imaging. Our approach achieves high resolution and high contrast CC imaging with single volume acquisition that takes <1 second, allowing rapid montaging and quantification over a 34° field of view. The proposed AO-OCTA method offers a more complete view of the outer retinal neurovascular complex, opening tremendous opportunities to investigate chorioretinal diseases.},
}
@article {pmid40808916,
year = {2025},
author = {Kayembe-Mulumba, B and Leffondré, K and Merle, BMJ and Korobelnik, JF and Helmer, C and Tzourio, C and Delcourt, C and Cougnard-Grégoire, A and Delyfer, MN},
title = {Long-Term Blood Pressure Variability and Risk of Age-Related Macular Degeneration in Older Adults: The ALIENOR Study.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100878},
pmid = {40808916},
issn = {2666-9145},
abstract = {PURPOSE: Long-term blood pressure variability (BPV) has emerged as a risk factor for various health problems, including eye diseases, independent of blood pressure (BP) levels. Yet, its role in age-related macular degeneration (AMD) progression remains unknown. This study aimed to assess associations between long-term BPV and the risk of AMD.<br><br>DESIGN: Prospective analysis of 14-year data from the ALIENOR (Antioxydants, LIpides Essentiels, Nutrition et maladies OculaiRes) study, a French longitudinal population-based cohort study (2006-2020).<br><br>PARTICIPANTS: The ALIENOR study included 963 participants aged &#x2265;73 years from the Three-City (3C) study in Bordeaux, for an ophthalmic follow-up.<br><br>METHODS: Systolic BPV (SBPV), diastolic BPV (DBPV), and pulse pressure variability (PPV) were determined as the standard deviation of available BP measurements in 3C visits (1999-2017).<br><br>MAIN OUTCOME MEASURES: Age-related macular degeneration was assessed using retinal color photographs and OCT imaging every 2 years from 2006 to 2020. Shared random effects joint models fitted BPV current values and quantified their effect on AMD onset. The implemented Bayesian approach yielded the mean of adjusted posterior hazard ratios of AMD and their 95% credibility intervals (CrIs).<br><br>RESULTS: Of the 692 (median age: 79.0 years; 63.5% female) and 475 (median age: 78.5 years; 61.1% female) at-risk participants, 10% and 36% developed advanced and intermediate AMD, respectively. The hazard of advanced AMD was significantly increased by 54% for a 5-mmHg increase in DBPV (adjusted hazard ratio [aHR]: 1.54, 95% CrI: 1.02-2.44), whereas statistical significance was not reached for a 5-mmHg increase in SBPV (aHR: 1.20, 95% CrI: 0.96-1.51) and PPV (aHR: 1.17, 95% CrI: 0.88-1.54). Conversely, BPV was not significantly associated with intermediate AMD (aHR: 0.96, 95% CrI: 0.83-1.11; aHR: 0.96, 95% CrI: 0.71-1.30; and aHR: 0.92, 95% CrI: 0.77-1.09; for a 5-mmHg increase in SBPV, DBPV, and PPV, respectively).<br><br>CONCLUSIONS: This study suggested that long-term variability in BP may be associated with an increased risk of advanced AMD, particularly for DBP. These findings underscore the need for further research to confirm this association, explore the underlying mechanisms, and propose potential interventions that could mitigate this risk.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40807033,
year = {2025},
author = {Jeong, A and Liang, H and Baek, SC and Sagong, M},
title = {Real-World Efficacy and Durability of Faricimab in Aflibercept-Resistant Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {15},
pages = {},
pmid = {40807033},
issn = {2077-0383},
abstract = {Objectives: This study aimed to evaluate the 6-month real-world outcomes of switching to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration (nAMD). Methods: A retrospective review was conducted on the eyes of 60 patients with aflibercept-resistant nAMD that were switched to faricimab. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including central subfield thickness (CST), subfoveal choroidal thickness (SFCT), and both the maximum height and width of pigment epithelial detachment (PED), at baseline and 1, 3, and 6 months after switching were evaluated. The type of PED and retinal fluid were also analyzed. Results: The results showed that BCVA remained stable at month 6 (p = 0.150), while CST significantly decreased (p = 0.020), and SFCT remained unchanged (p = 0.072). The maximum PED height significantly decreased (p = 0.030), while the maximum PED width did not change (p = 0.07). The mean injection interval significantly increased from 6.8 ± 2.4 weeks before switching to 11.2 ± 1.7 weeks after switching (p = 0.068). Furthermore, the dry macula rate was 43.3% at month 6. Conclusions: Switching to faricimab in aflibercept-resistant nAMD patients showed stable visual outcomes, significant anatomical improvements, and reduced treatment burden over 6 months in real-world clinical settings.},
}
@article {pmid40806887,
year = {2025},
author = {Kim, KE and Ahn, SJ},
title = {Visual Field Examinations for Retinal Diseases: A Narrative Review.},
journal = {Journal of clinical medicine},
volume = {14},
number = {15},
pages = {},
pmid = {40806887},
issn = {2077-0383},
support = {RS-2025-00561352//National Research Foundation of Korea/ ; },
abstract = {Visual field (VF) testing remains a cornerstone in assessing retinal function by measuring how well different parts of the retina detect light. It is essential for early detection, monitoring, and management of many retinal diseases. By mapping retinal sensitivity, VF exams can reveal functional loss before structural changes become visible. This review summarizes how VF testing is applied across key conditions: hydroxychloroquine (HCQ) retinopathy, age-related macular degeneration (AMD), diabetic retinopathy (DR) and macular edema (DME), and inherited disorders including inherited dystrophies such as retinitis pigmentosa (RP). Traditional methods like the Goldmann kinetic perimetry and simple tools such as the Amsler grid help identify large or central VF defects. Automated perimetry (e.g., Humphrey Field Analyzer) provides detailed, quantitative data critical for detecting subtle paracentral scotomas in HCQ retinopathy and central vision loss in AMD. Frequency-doubling technology (FDT) reveals early neural deficits in DR before blood vessel changes appear. Microperimetry offers precise, localized sensitivity maps for macular diseases. Despite its value, VF testing faces challenges including patient fatigue, variability in responses, and interpretation of unreliable results. Recent advances in artificial intelligence, virtual reality perimetry, and home-based perimetry systems are improving test accuracy, accessibility, and patient engagement. Integrating VF exams with these emerging technologies promises more personalized care, earlier intervention, and better long-term outcomes for patients with retinal disease.},
}
@article {pmid40806731,
year = {2025},
author = {Kisswani, D and Carroll, C and Valdes-Mora, F and Rutar, M},
title = {Epigenetic Alterations in Age-Related Macular Degeneration: Mechanisms and Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806731},
issn = {1422-0067},
support = {1165599//National Health and Medical Research Council/ ; },
mesh = {Humans ; *Macular Degeneration/genetics/metabolism/pathology ; *Epigenesis, Genetic ; DNA Methylation ; Proto-Oncogene Mas ; Animals ; RNA, Long Noncoding/genetics ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among the elderly, and is influenced by a combination of genetic and environmental risk factors. While genetic associations in AMD are well-established, the molecular mechanisms underlying disease onset and progression remain poorly understood. A growing body of evidence suggests that epigenetic modifications may serve as a potential missing link regulating gene-environment interactions. This review incorporates recent findings on DNA methylation, including both hypermethylation and hypomethylation patterns affecting genes such as silent mating type information regulation 2 homolog 1 (SIRT1), glutathione S-transferase isoform (GSTM), and SKI proto-oncogene (SKI), which may influence key pathophysiological drivers of AMD. We also examine histone modification patterns, chromatin accessibility, the status of long non-coding RNAs (lncRNAs) in AMD pathogenesis and in regulating pathways pertinent to the pathophysiology of the disease. While the field of ocular epigenetics remains in its infancy, accumulating evidence to date points to a burgeoning role for epigenetic regulation in AMD, pre-clinical studies have yielded promising findings for the prospect of epigenetics as a future therapeutic avenue.},
}
@article {pmid40806482,
year = {2025},
author = {Balzamino, BO and Biamonte, F and Micera, A},
title = {Biomolecular Aspects of Reelin in Neurodegenerative Disorders: An Old Candidate for a New Linkage of the Gut-Brain-Eye Axis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806482},
issn = {1422-0067},
mesh = {*Reelin Protein/metabolism ; Humans ; *Neurodegenerative Diseases/metabolism ; Animals ; *Brain/metabolism ; Alzheimer Disease/metabolism ; Gastrointestinal Microbiome ; Macular Degeneration/metabolism ; },
abstract = {Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut-brain-eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin's potential relation with the gut-brain and gut-brain-eye axes and providing novel attractive hypotheses on the gut-brain-eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss.},
}
@article {pmid40806264,
year = {2025},
author = {Hughes, D and Prestle, J and Zippel, N and McFetridge, S and Szczepan, M and Neubauer, H and Xu, H and Chen, M},
title = {Nintedanib Induces Mesenchymal-to-Epithelial Transition and Reduces Subretinal Fibrosis Through Metabolic Reprogramming.},
journal = {International journal of molecular sciences},
volume = {26},
number = {15},
pages = {},
pmid = {40806264},
issn = {1422-0067},
support = {xxxx//Boehringer Ingelheim/ ; },
mesh = {*Epithelial-Mesenchymal Transition/drug effects ; Animals ; Humans ; Fibrosis ; *Indoles/pharmacology ; Mice ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Transforming Growth Factor beta2/pharmacology/metabolism ; Cell Line ; Mice, Inbred C57BL ; Disease Models, Animal ; *Cellular Reprogramming/drug effects ; Metabolic Reprogramming ; },
abstract = {This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial-mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib's therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis.},
}
@article {pmid40803555,
year = {2025},
author = {Hong, AT and Luu, IY and Keenan, JD and Stewart, JM},
title = {Long-Term Metformin Use and Reduced Risk of Age-Related Macular Degeneration: A Large Database Study.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.07.018},
pmid = {40803555},
issn = {2468-6530},
abstract = {OBJECTIVE: To evaluate the association between metformin use and the risk of developing age-related macular degeneration (AMD) among patients with diabetes, with a focus on exposure duration and AMD subtypes.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients were identified from the TriNetX network using International Classification of Diseases, 10th Revision, and Current Procedural Terminology codes for diabetes and ophthalmic care. Patients aged &#x2265;60 years with diabetes and no documentation of AMD were included in the cohort.<br><br>METHODS: Patients were required to have no AMD diagnoses at 2 eye care visits &#x2265;1 year apart, with the second visit serving as the index event for analysis. The main exposure was yearly metformin use for &#x2265;5 years, with subanalysis up to 10 years. The outcome was incident AMD. Propensity score matching controlled for potential confounders, including demographics, comorbidities, medications, laboratory values, and health care utilization. The association between metformin and AMD was assessed using survival analysis. Results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs).<br><br>MAIN OUTCOME MEASURES: The primary outcome was a new diagnosis of AMD. Secondary outcomes included a new diagnosis of dry AMD and wet AMD.<br><br>RESULTS: After propensity score matching, the main cohort analysis included 7496 patients, of whom 3748 had &#x2265;5 consecutive years of metformin use. Incident AMD was documented in 122 (3.3%) patients who had been exposed to metformin and 184 (4.9%) who had not (HR, 0.68; 95% CI, 0.54-0.85). The metformin group had lower rates of both dry AMD (HR, 0.69; 95% CI, 0.53-0.90) and wet AMD (HR, 0.84; 95% CI, 0.50-1.39), although the association with wet AMD was not statistically significant. The metformin use for &#x2265;6 consecutive years showed consistent protective effects; 1 to 4 years showed weaker associations.<br><br>CONCLUSIONS: Prolonged metformin use in patients with diabetes was associated with a reduction in AMD risk in this claims database. These findings suggest a potential protective role for metformin, warranting further exploration of its long-term effects on AMD prevention.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40802977,
year = {2025},
author = {Carlà, MM and Scampoli, A and Grieco, G and Governatori, L and Catalani, R and Rizzo, S and Caporossi, T},
title = {Morphometric Changes In Macular Neovascularization Architecture After Faricimab Treatment In Neovascular Age-Related Macular Degeneration: Comparison Between Naïve And Switched Eyes.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004635},
pmid = {40802977},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate the morphometric changes in macular neovascularization (MNV) architecture after faricimab treatment in neovascular age-related macular degeneration (nAMD), comparing treatment-naïve and previously treated eyes.<br><br>METHODS: Prospective study analyzing 45 eyes (18 treatment-na&#xef;ve, 27 switched) with nAMD undergoing faricimab treatment. Optical coherence tomography angiography (OCTA) images were exported and the quantification of changes in MNV area, vessel area, vessel density, number of junctions, branching index, total vessel length, endpoints, and lacunarity was performed using AngioTool v0.6a. Follow-ups at baseline (V0), end of the loading phase (V1) and at one-year (V2) were collected.<br><br>RESULTS: Baseline MNV characteristics differed significantly between treatment-na&#xef;ve and switched eyes. Switched eyes exhibited greater MNV area (p<0.001), vessel area (p<0.001), junction count (p=0.004), vessel length (p<0.001), average vessel length (p=0.02), endpoint count (p=0.002), and lacunarity (p=0.04). Conversely, na&#xef;ve eyes had higher vessel density (p<0.001) and branching index (p=0.007). Post-treatment, MNV area (p<0.001), vessel area (p<0.001), junction count (p=0.001) and total vessel length (p<0.001) decreased, while lacunarity increased (p=0.001). Greater changes were observed in na&#xef;ve eyes, but the endpoint count only reduced in switched eyes (p=0.01), being stable in na&#xef;ve eyes. At V2, switched eyes still had larger MNV area (p=0.007), vessel area (p=0.004), junction count (p=0.002), vessel length (p=0.004), and endpoints (p=0.007).<br><br>CONCLUSION: Faricimab induces significant and sustained remodeling of the MNV network in nAMD, with more pronounced changes in treatment-na&#xef;ve eyes. These changes were primarily driven by the loading phase, but then remained stable toward the one-year follow-up.},
}
@article {pmid40802164,
year = {2025},
author = {Khodor, A and Caranfa, JT and Nanda, T and Ruiz-Lozano, RE and Quiroga-Garza, ME and Choi, S and Chehab, A and Ramos-Dávila, EM and Heier, JS and Shah, CP and Witkin, AJ},
title = {Correction: Functional and Anatomical Outcomes of Faricimab in Previously Treated Wet Age-Related Macular Degeneration: Systematic Review and Pooled Analysis.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {10},
pages = {2621},
doi = {10.1007/s40123-025-01224-w},
pmid = {40802164},
issn = {2193-8245},
}
@article {pmid40801672,
year = {2025},
author = {Ansari, G and Schärer, N and Pfau, K and Valmaggia, P and Gabrani, C and Zuche, H and Giani, A and Esmaeelpour, M and Yamaguchi, TC and Feltgen, N and Maloca, PM and Schmetterer, L and Scholl, HPN and Pfau, M},
title = {Evaluating the Progression of Retinal Sensitivity Loss in Geographic Atrophy Using Machine-Learning-Based Structure-Function Correlation (OMEGA 2).},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {34},
pmid = {40801672},
issn = {1552-5783},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Male ; *Geographic Atrophy/physiopathology/diagnosis ; Female ; Aged ; Tomography, Optical Coherence/methods ; *Machine Learning ; *Retina/physiopathology ; Disease Progression ; Visual Field Tests ; *Visual Fields/physiology ; Visual Acuity/physiology ; Middle Aged ; Aged, 80 and over ; Follow-Up Studies ; },
abstract = {PURPOSE: The purpose of this study was to evaluate the effectiveness of different machine-learning models in predicting retinal sensitivity in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and compare the progression of sensitivity loss using observed versus inferred data over time.<br><br>METHODS: Thirty patients with GA (37 eyes) were recruited for the OMEGA study. Participants underwent fundus-controlled perimetry (microperimetry) and spectral-domain optical coherence tomography (SD-OCT) imaging at baseline and follow-up visits at weeks 12, 24, and 48. Retinal layers were segmented using a custom-written deep-learning algorithm. We used various machine-learning models, including random forest, LASSO regression, and multivariate adaptive regression splines (MARS), to predict retinal sensitivity across three scenarios: (1) unknown patients, (2) known patients at later visits, and (3) interpolation within visits. Predictive accuracy was evaluated using the mean absolute error (MAE), and the models' ability to reduce test variability over time was analyzed using linear mixed models.<br><br>RESULTS: The random forest model demonstrated the highest accuracy across all scenarios, with an MAE of 3.67 decibels (dB) for unknown patients, 2.96 dB for known patients at follow-up, and 3.10 dB for within-visit interpolation. The inferred sensitivity data significantly reduced variability compared to the observed data in longitudinal mixed model analysis, with a residual variance of 2.72 dB&#xb2; versus 8.67 dB&#xb2;, respectively.<br><br>CONCLUSIONS: Machine-learning models, particularly the random forest model, effectively predict retinal sensitivity in patients with GA, with patient-specific baseline data improving accuracy for subsequent visits. Inferred sensitivity mapping presents a reliable, functional surrogate endpoint for clinical trials, offering high spatial resolution without extensive psychophysical testing.},
}
@article {pmid40801600,
year = {2025},
author = {Miller, RD and Mondon, I and Ellis, C and Muir, AM and Turner, S and Keeling, E and Wai, HA and Chatelet, DS and Johnson, DA and Tumbarello, DA and Lotery, AJ and Baralle, D and Ratnayaka, JA},
title = {Whole RNA-Seq Analysis Reveals Longitudinal Proteostasis Network Responses to Photoreceptor Outer Segment Trafficking and Degradation in RPE Cells.},
journal = {Cells},
volume = {14},
number = {15},
pages = {},
pmid = {40801600},
issn = {2073-4409},
support = {1/CX/CSRD VA/United States ; BB/T008768/1 to C.E//The BBSRC South Coast Doctoral Training Partnership/ ; RP-2016-07- 011//National Institute for Health and Care Research Professorship to D.B/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Proteostasis/genetics ; *Retinal Photoreceptor Cell Outer Segment/metabolism ; *RNA-Seq ; Lysosomes/metabolism ; Cell Line ; Protein Transport ; Proteolysis ; Autophagy/genetics ; RNA, Messenger/genetics/metabolism ; Transcriptome ; Gene Regulatory Networks ; },
abstract = {RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers were fed photoreceptor outer segments (POS), designed to be synchronously internalised, mimicking homeostatic RPE activity. Cells were subsequently fixed at 4, 6, 24 and 48 h when POS were previously shown to maximally co-localise with Rab5, Rab7, LAMP/lysosomes and LC3b/autophagic compartments. A comprehensive analysis of differentially expressed genes involved in proteolysis revealed a pattern of gene orchestration consistent with POS breakdown in the autophagy-lysosomal pathway. At 4 h, these included elevated upstream signalling events promoting early stages of cargo transport and endosome maturation compared to RPE without POS exposure. This transcriptional landscape altered from 6 h, transitioning to promoting cargo degradation in autolysosomes by 24-48 h. Longitudinal scrutiny of mRNA transcripts revealed nuanced differences even within linked gene networks. POS exposure also initiated transcriptional upregulation in ubiquitin proteasome and chaperone-mediated systems within 4-6 h, providing evidence of cross-talk with other proteolytic processes. These findings show detailed evidence of transcriptome-level responses to cargo trafficking and processing in RPE cells.},
}
@article {pmid40800716,
year = {2025},
author = {Robinson, K and Cooper, SJ and Persaud, S and Frederick, JL and Singh, RP},
title = {Discordance Among Patients and Ophthalmologists Regarding the Burden of Intravitreal Injections.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {2637-2645},
pmid = {40800716},
issn = {1177-5467},
abstract = {PURPOSE: To determine how patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) perceive their disease and its treatment and to assess the degree of alignment between patient and clinician perceptions.<br><br>PATIENTS AND METHODS: In June 2024 a survey of 101 patients (50 with DME and 51 with nAMD) and 100 ophthalmologists who treat these conditions completed surveys.<br><br>RESULTS: Sixty-six percent and 86% of patients with DME and nAMD, respectively, reported receiving intravitreal injections at least once every 8&#xa0;weeks. Eighty-two percent required a caregiver and/or public transportation to get to their appointments. The most significant symptoms for patients with DME were vision loss over time (2.89 out of 4.0) and blurred or double vision (2.76), and for those with nAMD were poor night vision (3.43), seeing in low-light conditions (3.27), and blurred vision (2.96). The proportion of patients who were dissatisfied with the education and counseling they received about their disease was greater for nAMD (31%) compared with DME (11%; P < 0.01). Ophthalmologists overestimated the extent to which patients perceived that injections were necessary (mean Likert scale score 3.41 vs 3.00; P < 0.01) and that patients experienced insurance barriers to receiving treatment (3.00 vs 2.46; P < 0.01). They overestimated the extent to which patients became less nervous with subsequent injections after the first (3.40 vs 2.94; P < 0.01) and underestimated their difficulty of getting to appointments (2.30 vs 2.64; P < 0.01).<br><br>CONCLUSION: This study highlights the significant burden experienced by patients undergoing intravitreal injections and identifies key areas of discordance between patient and clinician perceptions. Targeted education and counseling focused on these differences is indicated to improve patient satisfaction and outcomes.},
}
@article {pmid40800169,
year = {2025},
author = {Guo, B and Wang, D and Zhang, R and Hou, J and Liu, W and Wu, Y and Yang, X and Zhang, L},
title = {WaveAttention-ResNet: a deep learning-based intelligent diagnostic model for the auxiliary diagnosis of multiple retinal diseases.},
journal = {Frontiers in radiology},
volume = {5},
number = {},
pages = {1608052},
pmid = {40800169},
issn = {2673-8740},
abstract = {OBJECTIVE: This study constructs a deep learning-based combined algorithm named WaveAttention ResNet (WARN) to investigate the classification accuracy for seven common retinal diseases and the feasibility of AI-assisted diagnosis in this field.<br><br>METHODS: First, a deep learning-based classification network is constructed. The network is built upon ResNet18, integrated with the Convolutional Block Attention Module (CBAM) and wavelet convolution modules, forming the WARN method for retinal disease classification. Second, the public OCTDL dataset is used to train WARN, which contains classification data for seven retinal disease types: age-related macular degeneration (AMD), diabetic macular edema (DME), epiretinal membrane (ERM), normal (NO), retinal artery occlusion (RAO), retinal vein occlusion (RVO), and vitreomacular interface disease (VID). During this process, ablation experiments and significance tests are conducted on WARN, and comprehensive analyses of various indicators for WARN, ResNet-18, ResNet-50, Swin Transformer v2, EfficientNet, and Vision Transformer (ViT) are performed in retinal disease classification tasks. Finally, data provided by Shanxi Eye Hospital are used for testing, and classification results are analyzed.<br><br>RESULTS: WARN demonstrates excellent performance on the public OCTDL dataset. Ablation experiments and significance tests confirm the effectiveness of WARN, achieving an accuracy of 90.68%, F1-score of 91.29%, AUC of 97.50%, precision of 93.31%, and recall of 90.68% with relatively short training time. In the dataset from Shanxi Eye Hospital, WARN also performs well, with a recall of 90.85%, precision of 79.94%, and accuracy of 89.18%.<br><br>CONCLUSION: This study fully confirms that the constructed WARN is efficient and feasible for classifying seven common retinal diseases. It further highlights the enormous potential and broad application prospects of AI technology in the field of auxiliary medical diagnosis.},
}
@article {pmid40799657,
year = {2025},
author = {Hadzijahic, N and Kim, CK and Djulbegovic, MB and Antonietti, M and Taylor Gonzalez, DJ and Uversky, VN and Pulido, JS and Karp, CL},
title = {The effects of retinal disease on intrinsic protein disorder and liquid-liquid‑phase separation.},
journal = {Journal of proteins and proteomics},
volume = {},
number = {},
pages = {},
pmid = {40799657},
issn = {2524-4663},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND: The human retina is integral to vision, converting light into neural signals through a complex interplay of specialized neuronal cell types. Recent proteomic studies have revealed significant insights into retinal function, yet much of the retina's proteome remains unexplored. Our research focuses on quantifying and characterizing intrinsically disordered proteins (IDPs) and regions (IDRs) within the retina and other ocular structures. These proteins are critical for cellular processes due to their flexible, structure-less nature, allowing for versatile interactions in signaling and regulatory networks. Furthermore, we investigate the phenomenon of liquid-liquid-phase separation (LLPS), a process vital for cellular organization and implicated in various diseases, within the retina proteome.<br><br>METHODS: In this study, we employed a suite of bioinformatics and deep learning tools to analyze protein intrinsic disorder and the propensity for LLPS in proteomes from both healthy and diseased retinas. We utilized the Human Protein Atlas (HPA) as a baseline control, comparing it against the RetNet protein set and samples afflicted by age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) with and without gliosis. Protein sequences were sourced from the universal protein resource (UniProt) and analyzed for intrinsic disorder using the rapid intrinsic disorder analysis online (RIDAO) platform. Disorder levels and phase separation tendencies were further examined through statistical analyses, including ANOVA and chi-squared tests, to evaluate differences across proteomes. In addition, we assessed the likelihood of proteins to undergo LLPS using predictive tools, such as PSPredictor and ParSe V2, integrating these findings with intrinsic disorder data to draw comprehensive conclusions about the structural dynamics within these proteomes.<br><br>RESULTS: The HPA control proteome displayed the highest levels of intrinsic disorder, significantly greater than those observed in disease-specific proteomes, including those affected by AMD, glaucoma, and diabetic retinopathy with and without gliosis. CH-CDF plot analysis revealed distinct structural profiles, with a higher proportion of structured proteins in the HPA and molten globular states prevalent in disease states. Our findings highlight a marked disparity in LLPS propensity, with the HPA proteome and the RetNet Protein Set demonstrating the greatest potential, suggesting a disease-specific alteration in protein interaction dynamics and structural organization.<br><br>DISCUSSION: This study revealed significant variations in protein intrinsic disorder and liquid-LLPS across healthy and diseased retinal proteomes. The highest levels of disorder in the HPA proteome suggest a proteomic flexibility that is critical for normal retinal function. In contrast, the AMD and glaucoma proteomes, with their lower disorder and LLPS propensity, may lack this adaptability, potentially contributing to disease progression. These insights underscore the importance of protein dynamics in retinal disorders and point towards targeted therapies that could manipulate these properties to improve or maintain retinal health.},
}
@article {pmid40799295,
year = {2025},
author = {Ochoa, A and Brinson, J and Chin Loy, K and Yousuf, SJ},
title = {Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251362886},
pmid = {40799295},
issn = {2474-1272},
abstract = {Purpose: To investigate the association of cigarette-alternative tobacco products with age-related macular degeneration (AMD). Methods: The 2017 National Health Interview Survey, comprising epidemiologic data from a nationally representative sample of the US adult population, was queried to identify all participants who reported using electronic cigarettes (e-cigarettes) and smokeless tobacco and whether or not they had AMD. Participant characteristics were analyzed and a multivariable regression was performed to determine predictors of AMD, adjusting for age, sex, race/ethnicity, number of packs of cigarettes smoked per day, and body mass index. Results: The final analytic sample included 26 689 survey respondents, representing the US national population of 246 242 859 adults. The weighted prevalence of AMD was 1.9% (95% confidence interval [95% CI], 1.8-2.1%). Compared to those without AMD, adults with AMD were significantly older, more often female, and disproportionately non-Hispanic White (P < .0001). In adjusted models (including adjustment for number of packs of cigarettes smoked per day), the odds ratios for developing AMD were 1.49 (95% CI, 1.02 to 2.18) in adults who used smokeless tobacco products and 1.08 (95% CI, 0.73 to 1.60) in adults who used e-cigarettes, compared to those who had never used these products. Conclusions: This study identified smokeless tobacco use as a novel factor associated with AMD among a nationally representative sample, suggesting its avoidance may reduce the risk of developing AMD. Additional studies are needed to better understand the long-term effects of e-cigarettes on AMD.},
}
@article {pmid40798886,
year = {2025},
author = {Kim, YC and Kim, S and Kim, TW and Hong, SC and Seo, HJ and Jeong, JH and Lim, HK and Um, YH},
title = {Association Between Eye Diseases and Sleep Duration: A Nationwide Cross-Sectional Study.},
journal = {Psychiatry investigation},
volume = {22},
number = {9},
pages = {1038-1047},
pmid = {40798886},
issn = {1738-3684},
support = {2020R1I1A1A01057792//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; },
abstract = {OBJECTIVE: The visual system plays a crucial role in regulating sleep by providing cues that synchronize the circadian rhythm. Consequently, ophthalmic diseases-particularly diabetic retinopathy (DMR), age-related macular degeneration (AMD), epiretinal membrane (EM), and glaucoma-may influence sleep duration through circadian disruption and disease-related psychological stress. However, large-scale studies examining the relationship between these conditions and sleep duration remain limited. This study investigated these associations in a nationwide, population-based sample.<br><br>METHODS: This cross-sectional study analyzed data from the 2019 and 2020 the Korea National Health and Nutrition Examination Survey. Ophthalmic diseases were diagnosed through fundoscopy, and sleep duration on weekdays and weekends was self-reported. The study included 8,395 participants aged 40 years or older who underwent fundoscopy. Statistical models were adjusted for demographic and clinical covariates, including age, sex, body mass index, and comorbidities.<br><br>RESULTS: Patients with DMR and EM had significantly reduced sleep duration, with reductions of 0.3 hours to 0.5 hours on weekdays and weekends compared to individuals without these conditions. No significant differences in sleep duration were observed for AMD or glaucoma. After covariate adjustment, the associations between shorter sleep duration and DMR or EM remained significant.<br><br>CONCLUSION: This nationwide population-based study using fundus photography revealed that DMR and EM are significantly associated with reduced sleep duration, while AMD and glaucoma are not. These findings suggest a differential sleep impact by disease type and support the need for targeted evaluation and management of sleep in patients with ophthalmic diseases. Further research is warranted to clarify underlying mechanisms and guide public health strategies.},
}
@article {pmid40792095,
year = {2025},
author = {Arikan, D and Esfandiari, M and Zhang, P and Sommersperger, M and Dehghani, S and Taylor, RH and Ali Nasseri, M and Gehlbach, P and Navab, N and Iordachita, I},
title = {Towards Motion Compensation in Autonomous Robotic Subretinal Injections.},
journal = {... International Symposium on Medical Robotics. International Symposium on Medical Robotics},
volume = {2025},
number = {},
pages = {66-72},
pmid = {40792095},
issn = {2831-3690},
support = {R01 EB023943/EB/NIBIB NIH HHS/United States ; R01 EB025883/EB/NIBIB NIH HHS/United States ; R01 EB034397/EB/NIBIB NIH HHS/United States ; },
abstract = {Exudative (wet) age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, typically treated with intravitreal injections. Emerging therapies, such as subretinal injections of stem cells, gene therapy, small molecules and RPE cells require precise delivery to avoid damaging delicate retinal structures. Robotic systems can potentially offer the necessary precision for these procedures. This paper presents a novel approach for motion compensation in robotic subretinal injections, utilizing real time Optical Coherence Tomography (OCT). The proposed method leverages B[5]-scans, a rapid acquisition of small-volume OCT data, for dynamic tracking of retinal motion along the Z-axis, compensating for physiological movements such as breathing and heartbeat. Validation experiments on ex vivo porcine eyes revealed challenges in maintaining a consistent tool-to-retina distance, with deviations of up to 200 μm for 100 μm amplitude motions and over 80 μm for 25 μm amplitude motions over one minute. Subretinal injections faced additional difficulties, with phase shifts causing the needle to move off-target and inject into the vitreous. These results highlight the need for improved motion prediction and horizontal stability to enhance the accuracy and safety of robotic subretinal procedures.},
}
@article {pmid40791802,
year = {2025},
author = {Gómez-Benlloch, A and Widmer-Pintos, JN and Arnaldos-López, C},
title = {Reactive Orbital Myositis as a First Manifestation of Renal Cell Carcinoma.},
journal = {Case reports in ophthalmology},
volume = {16},
number = {1},
pages = {551-558},
pmid = {40791802},
issn = {1663-2699},
abstract = {INTRODUCTION: Orbital myositis (OM) is an inflammatory condition of the extraocular muscles, often idiopathic but occasionally associated with systemic diseases or malignancies. Secondary OM due to metastatic disease is rare. We report a case of OM as the initial manifestation of metastatic renal cell carcinoma, emphasizing the need for comprehensive evaluation of atypical ocular presentations.<br><br>CASE PRESENTATION: An 81-year-old male with a history of age-related macular degeneration presented with acute onset of pain and restricted movement in his left eye. Computed tomography imaging revealed an osteolytic lesion in the left sphenoid bone, causing reactive myositis. Further systemic evaluation identified a left renal mass with evidence of pulmonary and skeletal metastases. A core needle biopsy confirmed the diagnosis of metastatic renal cell carcinoma. Given the advanced disease stage, the patient was managed with palliative treatment. Despite medical interventions, he succumbed to the disease 6 months after symptom onset.<br><br>CONCLUSION: This case underscores the significance of considering malignancy in the differential diagnosis of OM, particularly in elderly patients with atypical ocular symptoms. Early recognition and systemic evaluation are crucial for timely diagnosis and management of underlying malignancies presenting with orbital involvement.},
}
@article {pmid40789472,
year = {2025},
author = {Cuello-Rodríguez, S and Blanco-Fernández, G and García-Otero, X and Díaz-Tome, V and Otero-Espinar, FJ and Seoane-Viaño, I},
title = {Long acting injectables &amp; implants: advances in intraocular drug delivery.},
journal = {International journal of pharmaceutics},
volume = {683},
number = {},
pages = {126058},
doi = {10.1016/j.ijpharm.2025.126058},
pmid = {40789472},
issn = {1873-3476},
mesh = {Humans ; *Drug Delivery Systems/methods ; Delayed-Action Preparations/administration &amp; dosage ; *Drug Implants/administration &amp; dosage ; Intravitreal Injections ; Animals ; *Eye Diseases/drug therapy ; Drug Liberation ; },
abstract = {The treatment of posterior segment ocular diseases, such as age-related macular degeneration and diabetic retinopathy, poses a significant challenge for ophthalmologists due to the eye's complex anatomy and physiological barriers. To overcome these challenges, intravitreal drug delivery offers a promising solution by enabling direct administration of therapeutic agents into the pathological area through an injection. However, these injections are highly invasive and carry several risks, including infection, retinal detachment, and increased intraocular pressure. As a result, considerable efforts have been directed toward developing drug delivery platforms (implants, nano- and microparticles, and hydrogels) capable of providing sustained drug release over extended periods. These long-acting systems aim to reduce the frequency of injections, thereby improving patient quality of life and decreasing the overall economic burden of treatment. This review provides an overview of intravitreal drug delivery systems, evaluating their clinical applicability and the potential challenges that must be addressed before they can be successfully translated into marketed drug products.},
}
@article {pmid40788858,
year = {2025},
author = {Montolío-Marzo, S and Pinazo, RG and Palacios-Pozo, E and Dolz-Marco, R},
title = {New Method to Facilitate Tomographic Macular Neovascularization Classification in Age-related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {9},
pages = {540-544},
doi = {10.3928/23258160-20250717-02},
pmid = {40788858},
issn = {2325-8179},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; *Wet Macular Degeneration/classification/diagnosis ; Aged ; Male ; *Choroidal Neovascularization/classification/diagnosis ; *Macular Degeneration/complications/classification/diagnosis ; Fluorescein Angiography ; Aged, 80 and over ; Reproducibility of Results ; },
abstract = {BACKGROUND AND OBJECTIVE: Evaluation of contrast-modified optical coherence tomography (OCT) images as a tool for better macular neovascularization (MNV) classification in age-related macular degeneration (AMD) cases.<br><br>PATIENTS AND METHODS: Twenty-five OCT images obtained with SPECTRALIS (Heidelberg Engineering GmbH) from patients showing MNV (10 type 1, 10 type 2, and 5 type 3) were selected. Two retina specialists (RDM and RGP) classified the MNV lesions and then the same cases were classified by 37 ophthalmologists with different degree of training. A grading tool was designed to classify these cases using standard OCT images (contrast value: 12) followed by reassessment with contrast-modified OCT images (contrast value: 1).<br><br>RESULTS: Thirty-seven ophthalmologists were involved: four 1st-year trainees, four 2nd-year trainees, four 3rd-year trainees, 12 4th-year trainees, and 13 consultants from different subspecialties. Average result for correct classification was 13.16 using standard images alone and 14.22 using contrast-modified images showing a significant improvement (P = 0.01). The accuracy was greater for type 1 lesions when using contrast-modified images, whereas there was no improvement with type 2 and 3 lesions (P = 0.039, P = 0.835, P = 0.193). The average correct answers was greater for type 2 (&#xb5; = 5.08) than type 1 (&#xb5; = 5.08) and type 3 (&#xb5; = 2) (P = 0.046). The graders (n; %) classified the utility of contrast-modified images as essential (1; 2,7%), very useful (29; 78.4%), indifferent (5; 13.5%), not very useful (1; 2.7%) and useless (1; 2.7%).<br><br>CONCLUSIONS: In challenging cases, it might be easier to locate the retinal pigment epithelium (RPE), evaluate RPE integrity, classify MNV, and study subretinal hyperreflective material using contrast enhanced OCT images. The accuracy for MNV classification increases with contrast-modified images in type 1 MNV. It is an accessible tool that could show even better performance as the ophthalmologist gains more experience using it.},
}
@article {pmid40788856,
year = {2025},
author = {Yao, CS and Lue, V and Stinnett, SS and Luhmann, UFO and Lad, EM},
title = {Association of National Eye Institute Visual Function Questionnaire 39 Scores With Visual Function in Age-related Macular Degeneration Over 24 Months.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {9},
pages = {526-533},
doi = {10.3928/23258160-20250717-01},
pmid = {40788856},
issn = {2325-8179},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Aged ; Surveys and Questionnaires ; *Macular Degeneration/physiopathology ; National Eye Institute (U.S.) ; United States ; *Sickness Impact Profile ; Aged, 80 and over ; Visual Fields/physiology ; Middle Aged ; Contrast Sensitivity/physiology ; Dark Adaptation/physiology ; Visual Field Tests ; Quality of Life ; Follow-Up Studies ; },
abstract = {BACKGROUND AND OBJECTIVE: The aim of this study was to determine the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ39) score association with visual function (VF) tests in early (eAMD) and intermediate (iAMD) age-related macular degeneration.<br><br>PATIENTS AND METHODS: Thirty-three eAMD, 47 iAMD, 21 control subjects completed the NEIVFQ39 at baseline and 22 eAMD, 31 iAMD, 17 control subjects at 24 months. Best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), cone contrast test (CCT), microperimetry (MP) with eye-tracking (MAIA), and dark adaptation (DA) testing were administered during both visits.<br><br>RESULTS: At baseline and 24 months, iAMD patients scored lower NEI-VFQ39 composite scores than eAMD participants and controls (P < 0.05); longitudinal changes showed no differences between groups. Baseline composite scores were associated with LLVA (Spearman-r = 0.33, P < 0.001), percent-reduced threshold (PRT) (r = -0.33, P = 0.001), and absolute threshold (AT) (r = 0.31, P = 0.003) on MP.<br><br>CONCLUSION: Although the NEI-VFQ39 did not detect change over 24 months, these results support the use of NEI-VFQ39 as a cross-sectional tool in iAMD.},
}
@article {pmid40785250,
year = {2025},
author = {Lewis-Luján, LM and Pérez Martínez, CJ and Iloki-Lewis, AP and Guerrero-Magaña, DE and Vargas-Durazo, J and Galvez-Ruiz, JC and Barnet, GF and Trujillo-López, S and Osadchuk, MA and Trushin, MV and Iloki-Assanga, SB},
title = {Role of Polyphenols in the Prevention and Treatment of Age-Related Macular Degeneration.},
journal = {Molecular nutrition &amp; food research},
volume = {69},
number = {21},
pages = {e70199},
doi = {10.1002/mnfr.70199},
pmid = {40785250},
issn = {1613-4133},
mesh = {Humans ; *Polyphenols/pharmacology/therapeutic use ; *Macular Degeneration/prevention &amp; control/drug therapy ; Antioxidants/pharmacology/therapeutic use ; Curcumin/pharmacology/therapeutic use ; Animals ; Oxidative Stress/drug effects ; Resveratrol ; Neuroprotective Agents/pharmacology ; Quercetin/pharmacology/therapeutic use ; Catechin/analogs &amp; derivatives/pharmacology ; Stilbenes/pharmacology/therapeutic use ; Dietary Supplements ; Anti-Inflammatory Agents/pharmacology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, driven by oxidative stress, inflammation, and mitochondrial dysfunction. Polyphenols-bioactive compounds in fruits, vegetables, tea, and wine-exert antioxidant, antiinflammatory, and neuroprotective effects, modulating key molecular pathways involved in AMD progression. This review highlights the mechanisms by which specific polyphenols such as resveratrol, curcumin, quercetin, and EGCG contribute to retinal protection. Preclinical and clinical studies support the integration of polyphenol-rich diets or supplements as potential strategies in AMD prevention and therapy.},
}
@article {pmid40785034,
year = {2025},
author = {Huang, Y and Zhou, Z and Huan, M and Guo, Q and Zhang, X and Lu, R and Chen, L and Li, X and Yao, J and Jiang, Q and Xu, Y},
title = {Superoxide Activates Ferroptosis via the Haber-Weiss Reaction and Enhances Age-Related Macular Degeneration.},
journal = {Aging cell},
volume = {24},
number = {10},
pages = {e70195},
pmid = {40785034},
issn = {1474-9726},
support = {81972742//National Natural Science Foundation of China/ ; 82271107//National Natural Science Foundation of China/ ; 82471111//National Natural Science Foundation of China/ ; BK20221186//Natural Science Foundation of Jiangsu Province/ ; },
mesh = {*Ferroptosis/drug effects ; *Macular Degeneration/metabolism/pathology ; Animals ; *Superoxides/metabolism ; Mice ; Humans ; Retinal Pigment Epithelium/metabolism/pathology ; Superoxide Dismutase/metabolism ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; },
abstract = {Antioxidant decline is crucial to driving age-related macular degeneration (AMD). Ferroptosis, a regulated cell death mediated by iron-dependent hydroxyl radical-catalyzed phospholipid peroxidation through the Fenton reaction, is implicated in various chronic degenerative diseases. Here, we show that superoxide activates ferroptosis in retinal pigment epithelium (RPE) cells via the Haber-Weiss reaction, thereby contributing to dry AMD. We silenced manganese superoxide dismutase (MnSOD/SOD2) in RPE cells and exposed the cells to blue light to induce ferroptosis by increasing superoxide anions. Additionally, MnSOD deficiency triggered the Hsp70-linked ubiquitin-dependent degradation of GPX4, further aggravating ferroptosis. We validated blue light-induced ferroptosis in the RPE layer as a driver of the dry AMD phenotype in Sod2[+/-] mice. Consequently, SOD mimetics efficiently protected RPE against phototoxicity by reducing superoxide-activated ferroptosis. Iron chelators or overexpressing GPX4 sufficiently eradicated ferroptosis. The finding reveals that excessive superoxide contributes to phospholipid peroxidation, providing a promising approach for preventing dry AMD by elevating MnSOD to inhibit RPE cell ferroptosis.},
}
@article {pmid40782305,
year = {2025},
author = {Doi, Y and Hata, M and Kawashima, Y and Tamiya, R and Ideyama, M and Kido, A and Miyata, M and Ueda-Arakawa, N and Tamura, H and Ooto, S and Ogino, K and Tsujikawa, A},
title = {One-year outcomes of three-monthly and four-monthly loading regimens of faricimab for treatment-naïve neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {11},
pages = {3073-3079},
pmid = {40782305},
issn = {1435-702X},
support = {21H03092//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence ; Aged ; Treatment Outcome ; Follow-Up Studies ; Fluorescein Angiography ; *Macula Lutea/pathology ; Time Factors ; Aged, 80 and over ; Dose-Response Relationship, Drug ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Choroid/pathology ; Drug Administration Schedule ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To compare the efficacy of different loading doses of faricimab by comparing the outcomes following four-monthly and three-monthly loading regimens in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients diagnosed with treatment-na&#xef;ve nAMD who received intravitreal injection of faricimab were retrospectively enrolled from clinical database at the Japanese Red Cross Wakayama Medical Center (JRCW) and Kyoto University Hospital (KUHP) between July 1, 2022, and April 31, 2023. Patients at JRCW and KUHP received four-monthly and three-monthly loading regimens, respectively. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and dry macula ratio were evaluated before initial treatment, two months after the final injection in the loading phase (Month 2) and one year after the initial treatment (Year 1). Dosing intervals were determined based on disease activity two and three months after the final injection of the loading phase.<br><br>RESULTS: This study included 24 and 25 eyes in the three-dose and four-dose groups, respectively. BCVA, CMT, and SFCT significantly improved in both cohorts at Month 2 (all P&#x2009;<&#x2009;0.01). After the loading phase, the doing intervals was similar between the two groups (P&#x2009;=&#x2009;0.58). These improvements were sustained through Year 1 (all P&#x2009;<&#x2009;0.01), with no significant differences in changes in BCVA, CMT, or SFCT between the groups at Year 1 (P&#x2009;=&#x2009;0.58, 0.50, and 0.41, respectively).<br><br>CONCLUSIONS: Morphological and functional efficacy over one year was comparable between the four- and three-dose faricimab loading regimens.<br><br>KEY MESSAGES: What is known Faricimab, a bispecific antibody targeting both VEGF-A and Ang-2, is emerging as a promising therapeutic for neovascular AMD. Although a four-dose loading regimen was adopted in the pivotal TENAYA and LUCERNE trials, its superiority over the more conventional three-dose protocol remains uncertain in clinical practice. What is new In this study, we directly compared the four- and three-monthly loading regimens and found no significant differences in the dosing intervals and morphological and functional efficacy at 1 year. For both typical age-related macular degeneration and polypoidal choroidal vasculopathy, the dosing intervals and morphological and functional efficacy were comparable between the four- and three-monthly loading regimens.},
}
@article {pmid40782213,
year = {2025},
author = {Terao, R and Obata, R and Okubo, A and Aoki, S and Azuma, K and Inoda, S and Hashimoto, Y and Yoshida, H and Misawa, M and Takahashi, H and Takahashi, H},
title = {Aqueous humor cytokine profile in insufficient responder to aflibercept for neovascular age-related macular degeneration.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {326},
pmid = {40782213},
issn = {1573-2630},
mesh = {Humans ; *Aqueous Humor/metabolism ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Female ; Male ; Prospective Studies ; *Cytokines/metabolism ; Aged ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/metabolism/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Follow-Up Studies ; Treatment Outcome ; Visual Acuity ; Tomography, Optical Coherence ; Middle Aged ; Biomarkers/metabolism ; },
abstract = {PURPOSE: To identify cytokines associated with insufficient response to aflibercept against neovascular age-related macular degeneration.<br><br>METHODS: This prospective, comparative control study enrolled 40 eyes of 40 patients with nAMD. Aqueous humor (AH) samples were collected at the baseline before the intravitreal administration of aflibercept. The patients were further classified into responder and non-responder groups based on the clinical course. Patients were classified as "responders" if they required three or fewer additional injections after the three initial monthly loading doses within one year, and as non-responders, if they required four or more injections after the initial three-monthly loading doses or were switched to alternative anti-VEGF agents or treatments such as photodynamic therapy. The concentration of Angiopoietin 1, angiopoietin like 4 (ANGPTL4), interferon gamma-induced protein 10, hepatocyte growth factor, interleukin 10, platelet derived growth factor BB, plasminogen activator inhibitor 1 (PAI1), vascular endothelial growth factor A, angiopoietin 2, monocyte chemotactic protein 1, IL8, IL12, platelet-derived growth factor (PlGF), and vascular cell adhesion molecule 1 in AH samples were analyzed using a multiplex immunoassay, in order to compare between responders and non-responders.<br><br>RESULTS: 21 eyes were defined as responders, and 19 eyes were defined as non-responders. There were no significant differences in baseline characteristics. Multiple variate analysis using logistic regression analysis found that PAI1 (p&#x2009;=&#x2009;0.023, coefficient&#x2009;=&#x2009;0.025), PlGF (p&#x2009;=&#x2009;0.016, coefficient&#x2009;=&#x2009;-&#x2009;1.4), and ANGPTL4 (p&#x2009;=&#x2009;0.032, coefficient&#x2009;=&#x2009;-&#x2009;0.00070) at the baseline were significantly associated with the resistance to aflibercept.<br><br>CONCLUSION: Baseline higher PAI1 and lower PlGF and ANGPTL4 were associated with insufficient response to aflibercept in 1&#xa0;year. These cytokines can potentially predict the treatment effect against nAMD.},
}
@article {pmid40781266,
year = {2025},
author = {Liu, S and Zhang, O and Wang, H and Zhou, S and Luo, P},
title = {Association between age-related macular degeneration and osteoporosis in US.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {29045},
pmid = {40781266},
issn = {2045-2322},
support = {GSP2-07//the Subject Fund of High-level Chinese Medicine Hospital of China Academy of Traditional Chinese Medicine/ ; WJZJ-202415//the construction project of high-level traditional Chinese medicine hospital, Wangjing Hospital, China Academy of Chinese Medical Sciences/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology/complications ; Female ; Male ; *Osteoporosis/epidemiology/complications ; Aged ; United States/epidemiology ; Cross-Sectional Studies ; Middle Aged ; Nutrition Surveys ; Bone Density ; Absorptiometry, Photon ; Risk Factors ; Aged, 80 and over ; },
abstract = {It has been hypothesized that there could be a potential link between low bone mineral density (BMD) and age-related macular degeneration (AMD). This hypothesis has prompted us to conduct a more in-depth exploration of whether an intrinsic association exists between the two. As a result, we undertook a cross-sectional study using the NHANES database to investigate the potential associations between osteoporosis and AMD. A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. AMD was determined by a standardized grading system based on the presence of key features of AMD in color photographs of the macula. The BMD of the spine and femur was assessed by dual-energy X-ray absorptiometry (DXA). Multivariate logistic regression analysis was performed to examine the relationship between osteoporosis and AMD after adjustment for potential confounders. To address potential non-linear relationships, restricted cubic spline regression was employed. Multivariate regression analysis revealed that osteoporosis was significantly associated with all types of AMD (early and late: OR, 2.25; P < 0.001), early AMD (OR, 2.05; P = 0.003) and late AMD (OR, 4.25; P = 0.022) in women. In men, osteoporosis was not associated with any type of AMD. In women, the status of osteoporosis in the total femoral, femoral neck, femoral trochanter and spine showed a nonlinear relationship with AMD (P for nonlinear<0.05). Our findings suggest that osteoporosis plays a role in AMD development in women.},
}
@article {pmid40779887,
year = {2025},
author = {Liu, F and Li, Q and Yang, Y and Lu, F},
title = {Visual cycle and LC3-associated phagocytosis in retina: regulatory mechanisms and therapeutic potential.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {190},
number = {},
pages = {118423},
doi = {10.1016/j.biopha.2025.118423},
pmid = {40779887},
issn = {1950-6007},
mesh = {Humans ; *Phagocytosis/physiology/drug effects ; Animals ; *Retina/metabolism/drug effects/pathology ; *Microtubule-Associated Proteins/metabolism ; *Vision, Ocular/physiology/drug effects ; },
abstract = {The visual cycle plays a pivotal dual role in retina, while it's essential for maintaining vision through continuous regeneration of the light-sensitive 11-cis-retinal chromophore. Its dysregulation contributes significantly to retinal degenerative disorders including age-related macular degeneration (AMD) and Stargardt disease. Recent advances have elucidated multiple therapeutic targets in visual cycle, ranging from inhibition of enzymatic activity of RPE65 and lecithin retinol acyltransferase (LRAT) to modulation of retinoid transport proteins and enhancement of protective LC3-associated phagocytosis. Pharmacological interventions of the visual cycle demonstrate promising results in reducing toxic retinoid accumulation, though clinical application faces challenges including nyctalopia, delayed dark adaptation, and dyschromatopsia. Future research directions emphasize the need for targeted visual cycle modulators that can selectively disrupt pathological processes without compromising essential visual function. This review summarizes the visual cycle and LC3-associated phagocytosis associated with various retinal diseases, highlights recent advances in pharmacological modulation of visual cycle, and aims to provide new insights into therapeutic strategies for retinal degenerative disorders.},
}
@article {pmid40778701,
year = {2025},
author = {Bora, K and Liu, CH and Kushwah, N and Maurya, M and Pavlovich, MC and Solt, LA and Sun, Y and Fu, Z and Akula, JD and Chen, J},
title = {Genetic Loss of RORα Impairs Visual Function With Rod Bipolar Cell Degeneration In Mice.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {20},
pmid = {40778701},
issn = {1552-5783},
support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01 EY017017/EY/NEI NIH HHS/United States ; R01 EY030140/EY/NEI NIH HHS/United States ; R01 DK135300/DK/NIDDK NIH HHS/United States ; R01 EY028100/EY/NEI NIH HHS/United States ; R01 DK136298/DK/NIDDK NIH HHS/United States ; R01 EY024963/EY/NEI NIH HHS/United States ; R01 EY031765/EY/NEI NIH HHS/United States ; R01 EY032492/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Electroretinography ; Mice ; *Retinal Bipolar Cells/pathology/metabolism ; *Nuclear Receptor Subfamily 1, Group F, Member 1/genetics/biosynthesis ; *Retinal Rod Photoreceptor Cells/pathology/metabolism ; Disease Models, Animal ; *Retinal Degeneration/genetics/physiopathology/metabolism/pathology ; Mice, Inbred C57BL ; Immunohistochemistry ; Mice, Knockout ; },
abstract = {PURPOSE: Retinoic acid receptor-related orphan receptor alpha (RORα) is a ligand-dependent nuclear receptor involved in eye development and diseases. Genetic variations of RORα have been linked with the development of age-related macular degeneration, yet whether RORα regulates visual function is unknown. In this study we investigated the role of RORα in regulating visual function in mice with genetic deficiency of RORα.<br><br>METHODS: ROR&#x3b1; deficient staggerer (Rorasg/sg) and age-matched wild type control mice were assessed for visual function using electroretinography (ERG). Retinal localization of ROR&#x3b1; and rod bipolar cell morphology were assessed using immunohistochemistry. Retinal thickness was measured as well as presence of retinal gliosis, and expression of genes in visual transduction.<br><br>RESULTS: ROR&#x3b1; is expressed in photoreceptors, retinal ganglion cells, and bipolar cells. Genetic deletion of ROR&#x3b1; in Rorasg/sg mice markedly impaired visual function measured by ERG, with substantial attenuation of b-wave amplitude compared with wild type controls, reflective of bipolar cell dysfunction. Rorasg/sg eyes showed significant degeneration of rod bipolar cells and retinal gliosis, both of which progressed upon aging. Moreover, loss of ROR&#x237a; also resulted in significant retinal thinning, including both outer and inner nuclear layers. Expression of genes involved in phototransduction and rod bipolar cell depolarization was upregulated in Rorasg/sg retinas, suggestive of potential compensatory remodeling of visual signaling.<br><br>CONCLUSIONS: Our findings demonstrate that ROR&#x3b1; is indispensable for the structural and functional maintenance of rod bipolar cells and could pose as a potential therapeutic target for mitigating bipolar cell deficits in retinal degenerative diseases.},
}
@article {pmid40778363,
year = {2025},
author = {Saeed, A and Guymer, RH and Hadoux, X and Jannaud, M and Dang, D and Hodgson, LAB and Glover, EK and Gee, EE and van Wijngaarden, P and Wu, Z},
title = {Targeted Defect-Mapping Microperimetry in Geographic Atrophy: A Sensitive Functional Outcome Measure for Intervention Trials.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100856},
pmid = {40778363},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the effectiveness of targeted defect-mapping microperimetry (DMP) for capturing progressive visual function loss in eyes with a small extent of geographic atrophy (GA).<br><br>DESIGN: Prospective longitudinal study.<br><br>PARTICIPANTS: Twenty-seven eyes from 25 participants with <0.75 disc areas of GA, seen over 145 visits in total.<br><br>METHODS: All participants underwent high-density targeted DMP testing of a 4&#xb0; radius region-of-interest. Two tests were performed at each visit, and participants were reviewed at 3-monthly intervals up to a 24-month period. Spearman rank correlations were calculated to assess structure-function relationships between the proportion of locations missed (PLM; nonresponse to 10-decibel stimuli) on each test and GA extent in the corresponding region tested. Targeted DMP outcome measures were derived based on evaluating the PLM from all test locations, or only from points adjacent to locations that were repeatably nonresponding on both baseline tests. These DMP outcome measures, and GA extent in the central 8&#xb0; radius region, were compared based on the coefficient of variation (CoV; representing performance for capturing longitudinal changes) and sample size requirements for trials powered to detect a &#x2265;30% treatment effect.<br><br>MAIN OUTCOME MEASURES: Correlation coefficients, CoV, and sample size estimates.<br><br>RESULTS: There was a strong and moderate structure-function correlation between the PLM on targeted DMP and GA extent in the corresponding region tested at the cross section and longitudinally, respectively (correlation coefficient = 0.88 and 0.57, respectively). Evaluating PLM from points &#x2264;0.5&#xb0; adjacent to repeatably nonresponding locations at baseline was the best-performing DMP outcome measure (CoV = 71%), which was comparable with evaluating GA extent in the central 8&#xb0; region (CoV = 80%). Evaluating this DMP outcome measure reduced the sample size of a 24-month trial by 46% compared with evaluating GA extent.<br><br>CONCLUSIONS: Targeted DMP testing can provide a sensitive functional outcome measure for trials that can capture longitudinal changes as effectively as measuring structural changes in eyes with a small extent of GA. The high structure-function correlations observed suggests that beneficial treatment effects on GA growth would likely be accompanied by corresponding evidence of functional benefit captured by targeted DMP testing.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40778359,
year = {2025},
author = {Liu, X and Yao, L and Hao, H and Wu, J and Jin, K and Gao, Q and Wang, X and Liao, D and Wang, N and Xiang, X and Chen, M and Zhao, Y and Ye, J},
title = {Assessment of Choriocapillaris in Healthy and Diseased Eyes Using 3-Dimensional Topographic Maps Based on OCT Angiography.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100828},
pmid = {40778359},
issn = {2666-9145},
abstract = {PURPOSE: To achieve clear in vivo imaging and systematic quantification of choriocapillaris (CC), enabling the exploration of age-related and disease-related changes of CC within a large sample size.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: A total of 1050 eyes from 727 individuals, comprising 633 healthy eyes, 277 eyes with age-related macular degeneration (AMD), and 140 eyes with high myopia.<br><br>METHODS: The 3-dimensional (3D) topographic maps of CC were obtained by performing image enhancement, depth reconstruction, and 3D rendering on a single OCT angiography enface image. Based on this map, we targeted key quantitative parameters to analyze vessel thickness, vascular complexity, vascular distribution uniformity, and blood perfusion of CC. We statistically analyzed the correlation between CC metrics and age in healthy population, as well as differences in CC metrics between healthy and diseased populations. To further explore the association between changes in CC and choroidal large vessels, we defined a parameter called "arterial zone (AZ) to venous zone (VZ) ratio" to assess the choroidal large-vessel perfusion.<br><br>MAIN OUTCOME MEASURES: The 3D topographic map of CC, 8 parameters of CC, and AZ/VZ.<br><br>RESULTS: The 3D topographic map effectively displayed the morphology of CC while maintaining high image accuracy. Statistical analysis revealed that with aging, the vessel thickness of CC in healthy eyes became thicker, and there was a decrease in vascular complexity, distribution uniformity, and perfusion. Additionally, AZ/VZ exhibited a trend of initial decline followed by an increase. In eyes with increasing severity of AMD, the vessel thickness of CC showed bidirectional changes followed by significant thickening. Complexity and distribution uniformity initially increased, followed by a marked decrease, whereas blood perfusion decreased initially before increasing. However, no significant intergroup differences in AZ/VZ were observed. In highly myopic eyes, compared to healthy eyes, the CC exhibited vessel thickening, reduced complexity and distribution uniformity, decreased perfusion, and a significant reduction in AZ/VZ.<br><br>CONCLUSIONS: This study explores age-related and disease-related CC changes via clear in vivo imaging and quantification. It aids understanding of CC states and may contribute to early disease diagnosis and prognosis.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40776277,
year = {2025},
author = {Deng, Q and Kishimoto, K and Sugiyama, O and Miyake, M and Tamura, H},
title = {Automatic Extraction of Images for Prognostic Prediction Models in Age-Related Macular Degeneration.},
journal = {Studies in health technology and informatics},
volume = {329},
number = {},
pages = {1878-1879},
doi = {10.3233/SHTI251260},
pmid = {40776277},
issn = {1879-8365},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/diagnosis ; Prognosis ; *Deep Learning ; *Image Interpretation, Computer-Assisted/methods ; },
abstract = {Age-related macular degeneration, one of the primary causes of blindness, requires effective prediction of mid-term treatment outcomes to support the ongoing administration of the standard therapy. Our previous work relied on specialist interpretation and manual extraction of images, which limits their applicability in broader practical application. To address this limitation, this study aims to develop a deep learning-based framework capable of automatically identifying an optimal "champion" image from a set of candidate images.},
}
@article {pmid40775583,
year = {2025},
author = {Ding, Y and Dong, Y and Wei, W},
title = {Protective Role of Erzhi Pills in H2O2-Induced Oxidative Stress, Inflammation, and Angiogenesis in ARPE-19 Cells.},
journal = {Biochemical genetics},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10528-025-11214-z},
pmid = {40775583},
issn = {1573-4927},
support = {81774370//National Natural Science Foundation of China (NSFC)/ ; },
abstract = {This research was purposed to explore the role and mechanism of Erzhi pills (EZP) in age-related macular degeneration (AMD). TCSMP, PubChem, SwissTargetPrediction, and TargetNet databases were utilized to identify the active ingredients and targets of EZP, while disease targets were obtained from the DISEASES and DisGeNET databases. All identified targets were standardized using the UniProt platform. Overlapping targets between the drug and disease were determined using the Jvenn tool, and these targets were subsequently imported into the STRING database for network analysis. Enrichment analyses were conducted using the gProfiler web tool. The hub gene network was constructed utilizing Cytoscape software. Molecular docking studies were performed to assess the interactions between key components and their respective targets. A total of 16 active ingredients and 310 targets of EZP were identified, with 46 targets overlapping with disease-related targets, which implicated pathways involving inflammatory response, angiogenesis, and HIF-1α signaling. The top five hub genes identified were KDR, STAT3, mTOR, ESR1, and HIF1A. In vitro experiments, the CCK-8 assay, DCFH-DA staining, ELISA, tube formation assay, RT-qPCR, and Western blot analysis were conducted to evaluate the cellular biological behaviors and protein expression levels. The results showed that EZP could reduce H2O2-induced ROS accumulation, proinflammatory cytokine release, and promote angiogenesis. EZP inactivated HIF-1α pathway. EZP might target HIF-1α pathway to suppress oxidative stress, inflammation, and angiogenesis in H2O2-exposed ARPE-19 cells.},
}
@article {pmid40774393,
year = {2025},
author = {Gao, J and Wang, W and Mo, Y},
title = {Retinal degenerative diseases: Complement system-microglia crosstalk.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.08.005},
pmid = {40774393},
issn = {1879-3304},
abstract = {Retinal degenerative diseases (RDD) are a group of age-related blinding eye diseases characterized by progressive degeneration and functional impairment of retinal photoreceptors or ganglion cells, for which there are currently no effective treatments. The complement system is an important innate immune system in the human body, activated through 3 pathways (classical pathway, lectin pathway, and alternative pathway) to ultimately form a membrane attack complex that acts on target cells. Microglia are the innate immune cells of the retina, responsible for maintaining retinal homeostasis. Complement system activation and microglial activation have been identified in RDD. Complement activation products C3 and C5 generate anaphylatoxins C3a and C5a, whose receptors C3aR and C5aR1 can activate microglia. Activated microglia can further produce complement C1q to activate the complement system, forming a positive feedback loop that exacerbates retinal damage. In this review, we focus on the crosstalk between the complement system and microglia in age-related macular degeneration, diabetic retinopathy, glaucoma, and pathological myopia-related retinal degeneration, and summarize clinical studies targeting the complement system and microglia for the treatment of RDD.},
}
@article {pmid40773002,
year = {2025},
author = {Hikichi, T and Kurabe, H and Notoya, A and Oguro, Y and Hirano, M and Doi, Y},
title = {Comparison of 1-year outcomes after switching to faricimab in neovascular age-related macular degeneration previously treated with anti-VEGF agents with/without a loading phase.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {40773002},
issn = {1613-2246},
abstract = {PURPOSE: To compare the 1-year outcomes after switching to faricimab with/without a loading phase of three monthly injections followed by a treat-and-extend (TAE) regimen in eyes with neovascular age-related macular degeneration previously treated with anti-VEGF agents.<br><br>STUDY DESIGN: Retrospective consecutive case study.<br><br>METHODS: Eyes with persistent exudative changes despite injection intervals of 10 weeks or less were switched to faricimab between June 2022 and December 2023 and included in this study. All eyes switched to faricimab between June 2022 and June 2023 received a single injection followed by a treat and extend (TAE) regimen (group 1). Thereafter, all eyes switched to faricimab received three consecutive monthly injections followed by a TAE regimen (group 2).<br><br>RESULTS: Of 153 eyes switched to faricimab, 21 eyes (17 in group 1, four in group 2) were excluded because of discontinuation of faricimab due to persistent exudative changes despite bimonthly injections; 132 eyes of 132 patients were analyzed. Faricimab treatment significantly improved the best-corrected visual acuity, anatomic parameters, with extended injection interval 1 year after the switch in 132 eyes and 45 eyes of group 2. That improvement, except the injection interval in 87 eyes of group 1, did not reach significance. The injection interval in group 2 was extended significantly compared with group 1 (P=0.023).<br><br>CONCLUSION: Switching to faricimab with a loading phase followed by a TAE regimen may improve outcomes in previously treated eyes. Further studies are warranted to confirm these findings.},
}
@article {pmid40772916,
year = {2025},
author = {Pastor-Idoate, S and Redruello-Guerrero, P and de Juan Hernández, L and Benites-Narcizo, G and Rivera-Izquierdo, M and García-Arumí, J and Pastor Jimeno, JC},
title = {Interventions for submacular haemorrhage: A systematic review and network meta-analysis of controversies-On behalf of the Spanish Vitreo-Retinal Society (SERV).},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.17570},
pmid = {40772916},
issn = {1755-3768},
abstract = {PURPOSE: This systematic review aims to evaluate and synthesize the existing literature on the interventions used for submacular haemorrhage (SMH), highlighting the controversies and differences in clinical practice.<br><br>METHOD: A systematic review was conducted following the PRISMA guidelines. A comprehensive search was performed across multiple databases, including MEDLINE, EMBASE and Cochrane Library, to identify studies on SMH treatment. Inclusion criteria encompassed randomized controlled trials, cohort studies and case series that focused on different therapeutic interventions. Data on functional outcomes, efficacy and safety of the interventions were extracted and analysed.<br><br>RESULTS: The review included 150 studies, of which 38 were included in the network meta-analysis. The analysis of best corrected visual acuity (BCVA) Included 26 studies, 20 interventions and 2125 eyes. Heterogeneity was moderate (I[2]&#x2009;=&#x2009;28.9%). Non-vitrectomy therapies showed better BCVA outcomes and fewer complications (e.g. retinal detachment, vitreous haemorrhage), while vitrectomy-based treatments achieved better anatomical results. According to P-score ranking, "Observation" had the highest probability of being most effective for BCVA (P-score&#x2009;=&#x2009;0.8051), followed by anti-VEGF monotherapy and non-vitrectomy combinations. However, this result should be interpreted cautiously, as the "Observation" group was based on only two studies (26 eyes) with clinical heterogeneity. No publication bias was detected (Egger's test p&#x2009;=&#x2009;0.582).<br><br>CONCLUSIONS: There is no consensus on a standard evidence-based treatment for SMH. Minimally invasive strategies are promising, but factors such as timing, lesion size and anti-VEGF use remain critical. Further large-scale randomised trials are needed to define optimal management.},
}
@article {pmid40771483,
year = {2025},
author = {Tian, M and Zhang, B},
title = {Identification of risk factors for the progression of age-related macular degeneration: a systematic review and meta-analysis of cohort studies.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1544765},
pmid = {40771483},
issn = {2296-858X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a retinal degenerative disease that primarily affects the elderly population and is a leading cause of vision loss in older adults. There is a lack of research comprehensively examining the risk factors for AMD progression. This study aimed to identify the risk factors influencing the development of AMD using a meta-analysis approach.<br><br>METHODS: We systematically searched the PubMed, Embase, and Cochrane Library databases from their inception until November 2024. Summary effect estimates were assigned as odds ratios (ORs) with 95% confidence intervals (CIs) using a random effects model. Further exploratory analyses included sensitivity and sub-group analyses.<br><br>RESULTS: Eighteen cohort studies involving 38,697 individuals were included in the final meta-analysis. We noted male versus female was associated with a reduced risk of AMD (OR: 0.84; 95% CI: 0.72-0.98; p&#x202f;=&#x202f;0.027). The identified risk factors for AMD included per 5-year increment in age (OR: 1.14; 95% CI: 1.09-1.19; p&#x202f;<&#x202f;0.001), current smoking (OR: 1.28; 95% CI: 1.07-1.52; p&#x202f;=&#x202f;0.007), alcohol intake (OR: 1.30; 95% CI: 1.00-1.67; p&#x202f;=&#x202f;0.046), per 1&#x202f;mmol/L increment in high-density lipoprotein (OR: 1.21; 95% CI: 1.08-1.36; p&#x202f;=&#x202f;0.001), total drusen >10% of the grid (OR: 7.85; 95% CI: 4.66-13.23; p&#x202f;<&#x202f;0.001), presence of depigmentation (OR: 6.39; 95% CI: 2.48-16.44; p&#x202f;<&#x202f;0.001), presence of hyperpigmentation (OR: 6.03; 95% CI: 1.94-18.73; p&#x202f;=&#x202f;0.002), and >10 small drusen (OR: 7.21; 95% CI: 2.10-24.72; p&#x202f;=&#x202f;0.002).<br><br>CONCLUSION: This study systematically identified the risk factors for AMD progression, and exploratory analyses were performed to determine the risk factors for early and late AMD. Patients at high risk of AMD should be monitored to improve modifiable risk factors and slow the progression of AMD.<br><br>INPLASY platform (INPLASY2024120036).},
}
@article {pmid40771083,
year = {2025},
author = {Mentzer, ZT and Park, YC and Zanjani, MB},
title = {Elucidating the Drug Delivery Mechanism in Porous Antibody Implants Using Molecular Simulations and Graph Theory.},
journal = {The journal of physical chemistry. B},
volume = {129},
number = {33},
pages = {8406-8413},
doi = {10.1021/acs.jpcb.5c02069},
pmid = {40771083},
issn = {1520-5207},
support = {R03 TR004429/TR/NCATS NIH HHS/United States ; },
mesh = {Porosity ; *Molecular Dynamics Simulation ; *Drug Delivery Systems ; *Antibodies/chemistry ; Drug Liberation ; *Drug Implants/chemistry ; },
abstract = {Drug delivery systems (DDSs) are utilized in the treatment of diseases by controlling the release rate of antibodies in a targeted location. One such form of DDSs is biodegradable polymer-based implants to circumvent traditional treatment processes such as antibody injections. In diseases such as macular degeneration, intravitreal injections are administered weekly/biweekly. These injections are painful for patients and prove to be inconvenient for obtaining transportation to and from appointments, as macular degeneration may cause partial blindness. In order to address this challenge, previous efforts have been made to create a biodegradable ocular DDS to administer antibody dosages over longer periods of time. In this work, a computational framework was developed to investigate the fundamental behavior and translocation of antibody agents through a porous membrane by employing molecular dynamics simulations and graph theory. Through this analysis, the results demonstrate that the release behavior of antibodies is highly correlated to the composition and geometric features of the pore network within the membrane. The computational models developed in this work provide insight into the design of long-term DDSs and can pave the way for future experiments that aim to improve the efficiency of polymer-based drug delivery systems.},
}
@article {pmid40769491,
year = {2025},
author = {Friedman, S and London, N and Hamouz, J and Kerényi, &#xc1; and Papp, A and Pregun, T and Chow, V and Bautista, B and Wang, D and Grachev, G and Franklin, J},
title = {Randomized Trial of Biosimilar ABP 938 Compared with Reference Aflibercept in Adults with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.07.015},
pmid = {40769491},
issn = {2468-6530},
abstract = {PURPOSE: To evaluate the clinical efficacy, safety, and immunogenicity of biosimilar ABP 938 compared with the aflibercept reference product (RP) in adults with neovascular (wet) age-related macular degeneration (nAMD).<br><br>DESIGN: A randomized, double-masked, active-controlled, multiregional clinical study.<br><br>PARTICIPANTS: A total of 579 patients with active treatment-na&#xef;ve choroidal neovascularization secondary to nAMD were randomized.<br><br>METHODS: Evaluable patients (N = 576) received 2 mg of ABP 938 (n = 288) or aflibercept RP (n = 288) by intravitreal injection every 4 weeks for the first 3 doses, then every 8 weeks through week 48. At week 16, the ABP 938 group continued on ABP 938 (n = 273), whereas the aflibercept RP group was rerandomized to continue on aflibercept RP (n = 136) or transition to ABP 938 (n = 134).<br><br>MAIN OUTCOME MEASURES: The primary efficacy end point was the least squares (LS) mean difference in change in best-corrected visual acuity (BCVA), measured by ETDRS letter score, from baseline to week 8. Secondary efficacy end points, safety, and immunogenicity were analyzed descriptively. In a substudy of patients, serum drug concentration profiles were assessed.<br><br>RESULTS: Demographic and baseline characteristics and exposure to treatment were similar between groups. Among initially randomized patients, the LS mean difference in change from baseline in BCVA at week 8 between ABP 938 and aflibercept RP was 0.1, with a 2-sided 95% confidence interval (CI: -1.3, 1.5) and 90% CI (-1.1, 1.3) falling within prespecified similarity margins (-3.9, 3.9, and -3, 3, respectively); thus, the primary clinical efficacy end point was met. Secondary efficacy end points (parallel-arm and posttransition) were overall similar between groups. No clinically meaningful differences were observed in the incidence of ocular and nonocular adverse events or events of interest. A low and similar incidence of binding antidrug antibodies was observed in all groups. The substudy confirmed low systemic exposure of free drug concentrations of ABP 938 and aflibercept RP.<br><br>CONCLUSIONS: This study supports the conclusion of no clinically meaningful differences in efficacy, safety, and immunogenicity between ABP 938 and aflibercept RP in patients with nAMD. Additionally, transitioning from aflibercept RP to APB 938 at week 16 resulted in comparable efficacy, safety, and immunogenicity between treatment groups.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40768461,
year = {2025},
author = {Khan, AA and Ahmad, KM and Shafiq, S and Akram, MU and Shao, J},
title = {ATLASS: An AnaTomicaLly-Aware Self-Supervised Learning Framework for Generalizable Retinal Disease Detection.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2025.3595697},
pmid = {40768461},
issn = {2168-2208},
abstract = {Medical imaging, particularly retinal fundus photography, plays a crucial role in early disease detection and treatment for various ocular disorders. However, the development of robust diagnostic systems using deep learning remains constrained by the scarcity of expertly annotated data, which is time-consuming and expensive. Self-Supervised Learning (SSL) has emerged as a promising solution, but existing models fail to effectively incorporate critical domain knowledge specific to retinal anatomy. This potentially limits their clinical relevance and diagnostic capability. We address this issue by introducing an anatomically aware SSL framework that strategically integrates domain expertise through specialized masking of vital retinal structures during pretraining. Our approach leverages vessel and optic disc segmentation maps to guide the SSL process, enabling the development of clinically relevant feature representations without extensive labeled data. The framework combines a Vision Transformer with dual-masking strategies and anatomically informed loss functions to preserve structural integrity during feature learning. Comprehensive evaluation across multiple datasets demonstrates our method's competitive performance in diverse retinal disease classification tasks, including diabetic retinopathy grading, glaucoma detection, age-related macular degeneration identification, and multi-disease classification. The evaluation results establish the effectiveness of anatomically-aware SSL in advancing automated retinal disease diagnosis while addressing the fundamental challenge of limited labeled medical data.},
}
@article {pmid40767441,
year = {2025},
author = {Huang, Z and Chen, C and Meng, J and Liu, S and Zhang, K and Du, Y and Zhu, X},
title = {Associations Among Sleep Duration, Sleep Quality, and Age-Related Ocular Diseases: Insights From Longitudinal and Mediation Analyses.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {15},
pmid = {40767441},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Aged ; Middle Aged ; Prospective Studies ; *Sleep Quality ; *Glaucoma, Open-Angle/epidemiology/physiopathology ; Incidence ; United Kingdom/epidemiology ; *Sleep/physiology ; Risk Factors ; *Diabetic Retinopathy/epidemiology/physiopathology ; *Cataract/epidemiology/physiopathology ; *Macular Degeneration/epidemiology/physiopathology ; Follow-Up Studies ; Time Factors ; Aged, 80 and over ; Proportional Hazards Models ; Sleep Duration ; },
abstract = {PURPOSE: To investigate the associations among sleep duration, sleep quality, and age-related ocular diseases, accounting for interactions with systemic inflammation.<br><br>METHODS: A total of 380,182 participants in the UK Biobank were included in this prospective population-based cohort study. The investigated exposures were sleep duration, sleep quality (quantified through an established algorithm comprised of five sleep traits), and traits including insomnia, daytime dozing, chronotype, and snoring. Outcomes were incidences of cataract, primary open-angle glaucoma (POAG), diabetic retinopathy (DR), and age-related macular degeneration (AMD). Cox proportional hazards models were used to estimate the hazard ratios (HRs), with mediation analysis of systematic inflammatory indicators further performed to explore potential mechanisms.<br><br>RESULTS: During a median follow-up of 12.6 years, 42,971 cataract cases, 5793 POAG cases, 4267 DR cases, and 7775 AMD cases were documented. Sleep duration displayed U-shaped relationships with cataract, POAG, and DR (all P nonlinear < 0.001), identifying 7 hours per day as optimal. Poor sleep quality also elevated the risks of cataract (HR = 1.17; P < 0.001) and POAG (HR = 1.21; P = 0.019), whereas for DR this effect was not significant but suggestive (HR = 1.15; P = 0.082). Sleep behavior traits including insomnia and daytime dozing were found to predict higher risks of these diseases. Mediation analysis indicated significant contributions of inflammatory indicators to the associations of poor sleep quality with cataract and DR.<br><br>CONCLUSIONS: Our findings suggest that sleep patterns might be modifiable risk factors for age-related ocular diseases and highlight the potential value of anti-inflammatory therapies to delay the manifestations of ocular aging.},
}
@article {pmid40767440,
year = {2025},
author = {Fragiotta, S and Parravano, M and Sacconi, R and Polito, MS and Cioffi, B and Rissotto, F and Beretta, F and Costanzo, E and Romano, E and Capuano, V and Souied, EH and Querques, G},
title = {Progression Patterns in Foveal-Sparing Geographic Atrophy With Double-Layer Sign Due to Neovascularization or Basal Laminar Deposits.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {11},
pages = {16},
pmid = {40767440},
issn = {1552-5783},
mesh = {Humans ; Retrospective Studies ; Male ; Tomography, Optical Coherence/methods ; Female ; *Fovea Centralis/pathology ; Aged ; Fluorescein Angiography/methods ; *Geographic Atrophy/diagnosis/etiology ; Disease Progression ; Aged, 80 and over ; Visual Acuity ; Fundus Oculi ; Middle Aged ; Prognosis ; *Retinal Neovascularization/diagnosis ; *Choroidal Neovascularization/diagnosis ; Follow-Up Studies ; },
abstract = {PURPOSE: The purpose of this study was to analyze the prognostic significance of double-layer sign (DLS) in eyes with foveal-sparing geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>METHODS: This retrospective, observational cohort study analyzed 46 eyes (46 patients) with foveal sparing GA and associated DLS, using fundus autofluorescence (FAF), near-infrared reflectance (NIR), optical coherence tomography (OCT), and OCT angiography (OCTA). DLS was defined based on OCTA findings as either thick basal laminar deposits (BLamD) or non-exudative macular neovascularization (NE-MNV). The area of GA and foveal sparing were estimated on both FAF and NIR at different time points. Centrifugal and centripetal GA growth rates referring to the lesion expansion away from and toward the fovea, respectively, were evaluated using a mathematical formula.<br><br>RESULTS: Of the 46 eyes enrolled, 25 had thick BLamD, whereas 21 had type 1 NE-MNV. The NE-MNV eyes showed significantly thicker DLS than those with BLamD (90.4 &#xb1; 39.8&#xa0;&#xb5;m vs. 57.0 &#xb1; 27&#xa0;&#xb5;m, 95% confidence interval [CI] = 0.34 to 0.78, P < 0.001). GA areas were smaller on FAF than NIR (95% CI = -0.89 to -0.03, P = 0.03) in the BLamD group, whereas no difference was observed in the NE-MNV group (95% CI = -0.37 to 0.64, P = 0.60). Despite similar GA areas, the NE-MNV eyes exhibited larger foveal sparing (95% CI = 0.02 to 1.21, P = 0.04). The foveal sparing area remained stable (F(1.2, 11 = 4.15, P = 0.06,&#xa0;&#x3c9;2 = 0.02) in the NE-MNV group, whereas a significant reduction was observed in the BLamD subgroup (F(1.39, 20.9) = 7.5, P < 0.001,&#xa0;&#x3c9;2 = 0.09).<br><br>CONCLUSIONS: OCTA has provided valuable insights into the pathogenic interpretation of the DLS signature. Our findings confirm that a neovascular DLS protects the retinal pigment epithelium and outer retina, contributing to prolonged foveal preservation.},
}
@article {pmid40766447,
year = {2025},
author = {Johnathon, S and Ke, J and Stephanie A, H and Maya, M and Bonilha, VL},
title = {Metabolic dysfunction promoted by mitochondrial DNA mutation burden drives retinal degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40766447},
issn = {2692-8205},
support = {F31 EY035133/EY/NEI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; },
abstract = {Retinal degenerative diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, and glaucoma, have been linked to mitochondrial dysfunction. However, the impact of mitochondrial DNA (mtDNA) mutation accumulation in the context of these retinopathies has yet to be thoroughly explored. Our previous studies focused on the retinal phenotype observed in the PolgD257A mutator mice (D257A), revealing the effects of aging and mtDNA mutation accumulation in the retina. We have reported that this model exhibited significant morphological and functional deficits in the retina by 6 months of age, with notable alterations in the retinal pigment epithelium (RPE) occurring as early as 3 months, including changes in the cristae density and reduction in length of mitochondria. This study investigated how mtDNA mutations affect the metabolic interaction between the retina and RPE in young (3 months) and old (12 months) wild-type (WT) and D257A mice. We assessed cellular energy production using freshly dissected retina samples from both groups through Seahorse analysis, immunofluorescence, and Western blot experiments. The analysis of aged D257A retina punches revealed significantly reduced basal and maximal mitochondrial respiration, along with increased mitochondrial reserve capacity compared to WT. However, glycolytic flux, measured as a function of extracellular acidification rate (ECAR), did not differ between WT and D257A mice. Both D257A retina and RPE exhibited decreased expression of essential electron transport proteins involved in oxidative phosphorylation. Additionally, we observed a reduction in the expression of glucose transporter 1 (GLUT-1) and lactate transporter (MCT1) at the apical surface of the RPE. Enzymes associated with glycolysis, including hexokinase II and lactate dehydrogenase A, were significantly lower in the aged D257A retina, while hexokinase I and pyruvate kinase 2 were upregulated in the RPE. These findings indicate that the accumulation of mtDNA mutations leads to impaired metabolism in both the retina and RPE. Furthermore, it suggests that glucose from the choroidal blood supply is being utilized by the RPE rather than being transported to the neural retina. Mitochondrial dysfunction in RPE promotes a glycolytic state in these cells, leading to reduced availability of metabolites and, consequently, diminished overall retinal function. These results are essential for advancing our understanding of the mechanisms underlying retinal degeneration and provide a new perspective on the role of mtDNA mutations in these diseases.},
}
@article {pmid40766039,
year = {2025},
author = {DeLucia, PR and Oberfeld, D and Kearney, JK and Cloutier, M and Jilla, AM and Zhou, A and Corona, ST and Cormier, J and Taylor, A and Wykoff, CC and Baurès, R},
title = {Time-to-Collision Estimation With Age-Related Macular Degeneration Using Visual and Auditory Cues: Which Cues are Most Important?.},
journal = {Proceedings of the Human Factors and Ergonomics Society ... Annual Meeting. Human Factors and Ergonomics Society. Annual meeting},
volume = {69},
number = {1},
pages = {1687-1688},
pmid = {40766039},
issn = {1071-1813},
support = {R01 EY030961/EY/NEI NIH HHS/United States ; },
abstract = {We measured time-to-collision (TTC) judgments from participants with age-related macular degeneration (AMD), and normal vision (NV) controls, with an audiovisual virtual reality system that simulated vehicles approaching in a 3D traffic environment. The vehicle was presented visually only, aurally only, or both simultaneously, allowing us to determine the relative importance of visual and auditory cues with psychophysical reverse correlation. Results indicated that TTC judgments were based on both auditory and visual cues in the AMD and NV groups; the AMD group relied, at least in part, on their residual vision. A multimodal advantage was not observed in either group. TTC estimation in the AMD group was surprisingly similar to that in the NV group. However, the AMD group showed a higher relative importance of "heuristic" cues compared to more reliably accurate cues favored by the NV group, suggesting that similar performance may be achieved through different cue-weighting strategies.},
}
@article {pmid40765005,
year = {2025},
author = {An, N and Liao, H and Zhang, C and Zeng, B and Liu, Z and Li, D and Huang, J and Liu, D and Qin, B},
title = {Association between dietary theobromine and age-related macular degeneration: results from NHANES 2005-2008 and in vitro experiments.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {714},
pmid = {40765005},
issn = {2047-783X},
mesh = {Humans ; *Macular Degeneration/epidemiology/metabolism ; Male ; *Theobromine/administration &amp; dosage ; Female ; Nutrition Surveys ; Middle Aged ; Reactive Oxygen Species/metabolism ; Heme Oxygenase-1/metabolism ; Aged ; Cell Proliferation/drug effects ; Superoxide Dismutase-1/metabolism ; *Diet ; Adult ; },
abstract = {OBJECTIVE: To investigate the relationship between theobromine and age-related macular degeneration (AMD) using a nationwide representative sample of adults and in vitro experiments.<br><br>METHODS: We analyzed data from the 2005-2008&#xa0;years of the National Health and Nutrition Examination Survey (NHANES), which included 5485 participants with available data on dietary theobromine intake and AMD. Multivariable logistic regression and smoothing curve fitting were used to examine the potential correlations. The inflection point was determined using a two-piecewise linear regression. Interaction tests and subgroup analyses were also conducted. In vitro experiments were conducted to investigate the effects of theobromine on cell proliferation, intracellular reactive oxygen species (ROS) levels, and the expression of heme oxygenase-1 (HO-1) and superoxide dismutase-1 (SOD-1) in a sodium iodate (NaIO3)-induced ARPE-19 cell injury model.<br><br>RESULTS: After controlling for potential confounding variables, the multivariate logistic regression model revealed an odds ratio of 0.73 (95% confidence interval: 0.56-0.98) for the association between dietary theobromine and AMD. The usage of smoothing curve fitting revealed a non-linear relationship, with an inflection point observed at 60&#xa0;mg/d (adjust OR&#x2009;0.31;95% CI 0.14-0.66). The negative correlation remained consistent across various demographic scenarios in subgroup analyses and interaction tests. In the NaIO3-induced ARPE-19 cell injury model, theobromine enhanced cell proliferation, reduced the expression of HO-1, and increased the expression of SOD-1.<br><br>CONCLUSIONS: A non-linear negative correlation between dietary theobromine and AMD was observed, and the antioxidant activity of theobromine was observed in vitro. Our findings suggest a potential association between higher theobromine intake and lower odds of AMD prevalence, which warrants further investigation of its therapeutic implications.},
}
@article {pmid40763014,
year = {2025},
author = {Chen, L and Zhou, X and Huang, C and Zhang, Y and Xin, C and Hong, J and Wang, Y},
title = {Engineered Un1Cas12f1 with boosted gene-editing activity and expanded genomic coverage.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {32},
pages = {e2501292122},
pmid = {40763014},
issn = {1091-6490},
support = {2023YFA0915000//Nation Key Research and Development Program of China/ ; 82273967//National Natural Science Foundation of China/ ; 2021QN020576//Department of Science and Technology of Guangdong Province/ ; 82425015//MOST | NSFC | National Science Fund for Distinguished Young Scholars (NSF for Distinguished Young Scholars)/ ; 82171102//National Natural Science Foundation of China/ ; 82271044//National Natural Science Fundation of China/ ; QWF158001//National Youth talent support program/ ; 22Y21900900//Shanghai Medical Innovation Research Program/ ; 24SG11//(the "Dawn" Program of) Shanghai Municipal Education Commission/ ; 24J22800500//Shanghai Science and Technology Innovation Action Plan for Cell and Gene Therapy/ ; 24CL2900802//Shanghai Science and Technology Innovation Action Plan for Advanced Materials/ ; 20254Z0019//Shanghai Municipal Commission of Health/ ; },
mesh = {Animals ; *Gene Editing/methods ; Mice ; Dependovirus/genetics ; Humans ; CRISPR-Cas Systems/genetics ; Genetic Vectors/genetics ; PTEN Phosphohydrolase/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics ; Genetic Therapy/methods ; HEK293 Cells ; },
abstract = {Compact programmable nucleases provide versatile genome editing tools with therapeutic potential, particularly when delivered via adeno-associated virus (AAV) vectors. However, their limited editing efficacy and stringent protospaceradjacent motif (PAM) requirements impose significant limitations in practical application. Here, we engineered MiniCasUltra, an optimized Un1Cas12f1 variant, through rational mutagenesis. MiniCasUltra exhibits sixfold higher editing activity than Un1Cas12f1, minimal off-target effects (on/off-target ratio > 10), and an expanded PAM preference (5'-WBTR). Using a single AAV vector encoding MiniCasUltra and two single-guide RNAs, we achieved simultaneous editing of two disease-causing genes (Pten and Fah) in mouse liver, with indel rates of 15.82% and 29.39%, respectively- significantly surpassing CasMINI V3.1 (3.45% and 10.98%). Furthermore, AAV delivery of MiniCasUltra targeting a noncanonical 5'-TCTG PAM site in human vascularendothelial growth factor A reduced choroidal neovascularization (CNV) lesions in a laser-induced CNV mouse model of neovascular age-related macular degeneration, a leading global cause of blindness. The broad and effective targeting capabilities of MiniCasUltra, coupled with its compact size, highlight its potential for in vivo genome editing and therapeutic interventions.},
}
@article {pmid40762817,
year = {2025},
author = {Stark, KJ and Zimmermann, ME and Helbig, H and Heid, IM and Brandl, C},
title = {Central retinal volume derived from optical coherence tomography as a potential predictor of mortality in the old-aged population- results from the German AugUR study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {10},
pages = {2737-2746},
pmid = {40762817},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Aged, 80 and over ; Germany/epidemiology ; Prospective Studies ; *Retina/pathology/diagnostic imaging ; Cause of Death/trends ; Follow-Up Studies ; Organ Size ; *Population Surveillance/methods ; Survival Rate/trends ; Risk Factors ; },
abstract = {PURPOSE: To estimate mortality risk depending on central retinal volume (CRV) from optical coherence tomography (OCT) in a German cohort of the old-aged population.<br><br>METHODS: In the AugUR study, a prospective population-based cohort study in individuals aged 70-95 years at baseline, we conducted multimodal retinal imaging, including spectral-domain OCT. Heidelberg Spectralis-derived CRV measurements from first examinations of 2,166 participants were included in the analyses. Within the observation period (median 5.9-years), 374 participants died. Association between CRV at baseline and mortality was analysed with Kaplan-Meier curves and Cox proportional hazard regression.<br><br>RESULTS: Decrease in CRV was associated with increased all-cause mortality risk. In a full model with age, sex, body weight, body size, OCT scan focus, age-related macular degeneration, smoking, cardiovascular disease, diabetes, and hypertension, hazard ratio per standard deviation lower CRV was 1.17. Cardiovascular death was not associated with CRV in the full model. However, other causes for death except cardiovascular reasons showed association with lower CRV (hazard ratio 1.25). In addition, the association was significant in those who had already exceeded their expected life expectancy (hazard ratio 1.21) but not in women below 83 years and men below 78 years, respectively.<br><br>CONCLUSION: This study indicates that lower CRV, which can be easily and automatically derived from OCT images, is a potential predictor for mortality in the old-aged population. This effect occurs independently of cardiovascular disease.},
}
@article {pmid40762815,
year = {2025},
author = {Alsakran, WA and Alsadoon, AA and Alsayed, B and Magliyah, MS and ALBalawi, HB},
title = {Clinical features and classification framework of polypoidal choroidal vasculopathy in Saudi populations.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {323},
pmid = {40762815},
issn = {1573-2630},
mesh = {Humans ; Saudi Arabia/epidemiology ; Retrospective Studies ; Male ; Female ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; *Visual Acuity ; Aged ; *Polyps/diagnosis/classification/epidemiology ; Fundus Oculi ; Middle Aged ; *Choroid/blood supply ; *Choroidal Neovascularization/diagnosis/classification/epidemiology/therapy ; Photochemotherapy/methods ; Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Polypoidal Choroidal Vasculopathy ; },
abstract = {INTRODUCTION: The Changes in visual acuity(VA) can be caused by polypoidal choroidal vasculopathy(PCV), a subtype of macular neovascularization which is characterized by the formation of polyp-like structures under the retinal pigment epithelium. PCV has been commonly found concurrent with the neovascular age-related macular degeneration (nAMD), which has led to the debate regarding whether, it should be viewed as an independent entity or as a subset of nAMD. The insight into the clinical features of PCV and its therapeutic response such as understanding the prognosis of this disease is very crucial for management and better outcomes. This study aims to differentiate the different types of PCV, and assess its clinical features, disease progression, and treatment options available for Saudi patients and also examine the effectiveness of different treatment modalities.<br><br>MATERIALS AND METHODS: A retrospective study was conducted in Saudi Arabia among 39 PCV diagnosed patients, using multimodal imaging technique for assessment such as fundus imaging, OCT and ICGA. Patients were classified into three subtypes: age-related macular degeneration-associated PCV(PCV-AMD, Type A), a group with posterior-capsule-vitreous neovascularization-associated PCV (PCV-BVN, Type B), and idiopathic PCV (Type C). The treatment options available were photodynamic therapy(PDT), thermal laser therapy and anti-vascular endothelial growth factor (anti-VEGF) therapy. The clinical&#x2002;and visual outcomes were evaluated at the end of 1&#xa0;year. SPSS version 23 was used to conduct statistical analysis, including chi-square, ANOVA and Kruskal-Wallis&#x2002;tests (p&#x2009;<&#x2009;0.05).<br><br>RESULTS: PCV-AMD was the most common subtype(75.7%), followed by PCV-BVN (13.5%) and idiopathic PCV (10.8%). The median age was 68&#xa0;years, with idiopathic PCV patients being significantly younger (p&#x2009;=&#x2009;0.012). Most lesions were macular (94.6%) with peaked/dome-shaped RPE elevations (94.6%). Anti-VEGF therapy was administered in 94.6% of cases, with aflibercept usage differing significantly across subtypes (p&#x2009;=&#x2009;0.018). Complete lesion resolution was achieved in 45.9%, with PCV-BVN showing the highest resolution rate (80%) and idiopathic PCV the lowest at(0%).<br><br>CONCLUSION: PCV is predominantly presents as a variant of nAMD, with significant differences in subtype characteristics and treatment response. While anti-VEGF therapy remains the mainstay of treatment, idiopathic PCV appears more refractory, necessitating the individualized therapeutic strategies. Additional future studies are required to enhance management strategies for this condition.},
}
@article {pmid40761529,
year = {2025},
author = {Sheth, JU and Bhopalka, AK and Meshram, B and Karande, S},
title = {Quantitative Assessment of En‑face OCT‑Derived Minimum Intensity Fluid Changes Following Ranibizumab Biosimilar Therapy in Macular Neovascularization Secondary to nAMD and PCV.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {2505-2512},
pmid = {40761529},
issn = {1177-5467},
abstract = {PURPOSE: This retrospective study aimed to evaluate the efficacy of a new regulatory approved ranibizumab biosimilar (RzB), Oceva[®] (Sun Pharmaceutical Industries Limited, Mumbai, India), in treating macular neovascularization secondary to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), using Minimum-Intensity based changes observed on en-face optical coherence tomography (OCT) (en-face MI OCT).<br><br>PATIENTS AND METHODS: Thirty-six eyes with treatment-na&#xef;ve MNV underwent three loading doses of RzB. Best-corrected visual acuity (BCVA) and the proportions of eyes with subretinal fluid (SRF), intraretinal fluid (IRF), and subretinal hyperreflective material (SHRM) were assessed. En-face MI OCT-based analysis was conducted to quantify changes in fluid area and perimeter.<br><br>RESULTS: At 12&#xa0;weeks, there was a statistically significant improvement in BCVA from 0.94 {&#x2248;20/174}
(&#xb1; 0.59) logMAR to 0.84 {&#x2248;20/138}
(&#xb1; 0.61) logMAR (P=0.04). En-face MI OCT revealed a significant reduction in the median area of fluid from 0.9 mm&#xb2; (IQR 0.62-4.56) to 0.32 mm&#xb2; (IQR 0.1-0.64) (P=0.007), and in the median perimeter of fluid from 10.95 mm (IQR 7.26-25.67) to 6.02 mm (IQR 1.76-7.93) (P=0.0005). The proportion of eyes with SRF, IRF, and SHRM decreased from baseline (83.33%, 66.67%, and 58.33% respectively) to 12&#xa0;weeks (58.33% [P=0.015], 38.89% [P=0.013], and 13.89% [P<0.001]). No adverse events were reported.<br><br>CONCLUSION: Treatment with the novel RzB showed promising outcomes in improving visual parameters and reducing fluid accumulation in patients with MNV secondary to nAMD and PCV. Minimum Intensity-based analysis provided detailed insights into fluid dynamics, demonstrating its utility in evaluating treatment responses in MNV. This study contributes to the initial assessment of RzB in clinical practice, highlighting its potential efficacy in managing MNV.},
}
@article {pmid40760090,
year = {2025},
author = {Su, B and Sun, Y and Yu, W and Wang, C and Xia, Q and Zhu, Y},
title = {Exploring the causal relationship between 16 eye diseases and stroke and their subtypes from a genome-wide perspective.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {28357},
pmid = {40760090},
issn = {2045-2322},
mesh = {Humans ; *Genome-Wide Association Study ; *Eye Diseases/genetics/complications ; *Stroke/genetics/complications/epidemiology ; Mendelian Randomization Analysis ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide ; },
abstract = {There is increasing evidence that eye diseases and stroke frequently co-occur, but the causal relationships remain elusive. Therefore, Mendelian randomization was used to investigate possible causal relationships between eye diseases and stroke (including its subtypes). This study utilized large-scale genome-wide association study pooled genetic data from two major databases: the IEU OpenGWAS project and the FinnGen databases. We then screened for instrumental variables that met the following three conditions: showing strong associations with the exposure factors, being independent of each other and independent of any confounders, and excluding instrumental variables to ensure that the F-value was greater than 10, and used the Inverse Variance Weighted (IVW) method to conduct causal analyses using the weighted median method, MR-Egger method, MR- PRESSO test and leave-one-out sensitivity test to test the robustness, heterogeneity and horizontal pleiotropy of the results. In order to control for the false positive rate in multiple hypothesis testing, a False Discovery Rate (FDR) correction was also performed. A total of 16 eye diseases and strokes and their subtypes were investigated in this study. In the IVW model, the MR study showed a total of 20 IVWs with p-values less than 0.05. We excluded 6 results with heterogeneity or pleiotropy by sensitivity analysis, and finally the following reliable results were left: (1) patients with age-related macular degeneration had a 5%, 2%, and 7% lower risk of subarachnoid hemorrhage, ischemic stroke, and small-vessel stroke; (2) patients with keratitis had a 12% higher risk of cardioembolic; (3) patients with optic atrophy had a 3% higher risk of stroke; (4) patients with amblyopia had a 3% higher risk of stroke; and (5) patients with other inflammation of eyelid had a small-vessel had a 20% elevated risk; (6) patients with ptosis of the eye had a 17% elevated risk of cardioembolic; (7) patients with strabismus have a 23% elevated risk of small-vessel; (8) patients with stroke had a refractive error by 17%; (9) patients with intracerebral hemorrhage had a 15% increased risk of uveitis; (10) patients with IS had an 11% increased risk of diabetic retinopathy; (11) patients with large-artery atherosclerosis had a 2% increased risk of glaucoma; (12) patients with cardioembolic had a 24% increased risk of amblyopia. From a genetic standpoint, keratitis, amblyopia, other eyelid inflammations, ptosis and strabismus are associated with increased risks of the risk of stroke or its subtypes. Conversely, age-related macular degeneration is associated with reduced risks of the risk of stroke or its subtypes. Furthermore, stroke or its subtypes increase the risks of refractive error, uveitis, diabetic retinopathy, glaucoma, and amblyopia. Nevertheless, it is imperative that these causal relationships be subjected to further verification through fundamental research and Randomized Controlled Trial (RCT).},
}
@article {pmid40758327,
year = {2025},
author = {Grosso, F and Zanetti, D and Sanna, S},
title = {Causal relationships between gut microbiome and hundreds of age-related traits: evidence of a replicable effect on ApoM protein levels.},
journal = {Aging},
volume = {17},
number = {8},
pages = {1966-1987},
pmid = {40758327},
issn = {1945-4589},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Apolipoproteins M/metabolism/genetics/blood ; *Aging/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Male ; Aged ; Female ; },
abstract = {In the past 20 years, the involvement of gut microbiome in human health has received particular attention, but its contribution to age-related diseases remains unclear. To address this, we performed a comprehensive two-sample Mendelian Randomization investigation, testing 55130 potential causal relationships between 37 traits representing gut microbiome composition and function and age-related phenotypes, including 1472 inflammatory and cardiometabolic circulating plasma proteins from UK Biobank Pharma Proteomic Project and 18 complex traits. A total of 91 causal relationships remained significant after multiple testing correction (false discovery rate p-value <0.05) and sensitivity analyses, notably two with the risk of developing age-related macular degeneration and 89 with plasma proteins. The link between purine nucleotides degradation II aerobic pathway and apolipoprotein M was further replicated using independent genome-wide association study data. Finally, by taking advantage of previously reported biological function of Faecalibacterium prausnitzii we found evidence of regulation of six proteins by its function as mucosal-A antigen utilization. These results support the role of gut microbiome as modulator of the inflammatory and cardiometabolic circuits, that may contribute to the onset of age-related diseases, albeit future studies are needed to investigate the underlying biological mechanisms.},
}
@article {pmid40757768,
year = {2025},
author = {Chen, H and Xu, N and Rao, H},
title = {Serum Uric Acid and Intermediate Age-Related Macular Degeneration: A Nationally Representative Study in the United States.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {8},
pages = {6},
pmid = {40757768},
issn = {2164-2591},
mesh = {Humans ; *Uric Acid/blood ; Male ; Female ; United States/epidemiology ; Middle Aged ; Aged ; *Macular Degeneration/blood/epidemiology ; Nutrition Surveys ; *Hyperuricemia/blood/epidemiology ; Risk Factors ; Cross-Sectional Studies ; },
abstract = {PURPOSE: The purpose of this study was to investigate the associations between serum uric acid (SUA) levels and intermediate age-related macular degeneration (iAMD) in the United States population.<br><br>METHODS: This study included data from the 2005 to 2008 National Health and Nutrition Examination Survey. Weighted logistic regression models (crude, partially adjusted, and fully adjusted) were used to assess linear associations between SUA levels and iAMD. Restricted cubic spline (RCS) analysis tested nonlinear associations. Subgroup analyses stratified by age, sex, and race/ethnicity further explored potential effect modifiers.<br><br>RESULTS: Among 3208 participants aged &#x2265;50 years, 420 (11.2%) had iAMD and 766 (22.3%) exhibited hyperuricemia (HUA). Logistic regression models showed no significant associations between SUA levels and the odds of developing iAMD across all three models. In the fully adjusted model, the odds ratio (OR) comparing the highest to the lowest SUA quintile was 0.95 (95% confidence interval [CI] = 0.53-1.70, P = 0.84). The trend test indicated no significant increase in the odds of iAMD across quintiles of SUA levels (P for trend = 0.60). Similarly, no significant association was found when SUA values were categorized as HUA or non-HUA (P = 0.66). RCS analysis did not demonstrate a nonlinear relationship between SUA levels and iAMD risk. Subgroup analyses showed no significant differences across age, sex, and race/ethnicity stratifications.<br><br>CONCLUSIONS: Elevated SUA levels were not associated with increased iAMD risk in this large, nationally representative sample.<br><br>TRANSLATIONAL RELEVANCE: Our study provides insights into the relationship between SUA levels and iAMD, challenging "hyperuricemic AMD" and offering valuable implications for clinical risk assessment.},
}
@article {pmid40755970,
year = {2025},
author = {Nguyen, MD and Fekrat, R and Gee, C and Demirci, AN and Kharabaf, S and Le, D and Tadros, M and Nguyen, VQ and Patel, S and Truong, T and Ahdoot, R and Kurtz, IB and Kerr, M and Massoud, A and Hanna, R},
title = {Intravitreal vascular endothelial growth factor inhibitor systemic and renal toxicity registry.},
journal = {Clinical kidney journal},
volume = {18},
number = {8},
pages = {sfaf206},
pmid = {40755970},
issn = {2048-8505},
abstract = {BACKGROUND: Intravitreal vascular endothelial growth factor inhibitors (IVEGFi) are used in the treatment of diabetic retinopathy, age-related macular degeneration (AMD) and central retinal vein obstruction. As we have previously reported, there are an increasing number of cases documenting IVEGFi with renal injury and increased concentrations in the serum. To assess this claim, we have developed a novel reporting system through an electronic registry for cases of suspected VEGFi injury.<br><br>METHODS: A website with multiple data protection sets was created to educate, promote awareness and capture patient cases of suspected IVEGFi toxicity. The website displays the molecular biology of VEGF signaling, the process of absorption into the bloodstream, and study reports showing risks on case, cohort and epidemiologic levels. A Health Insurance Portability and Accountability Act (HIPAA)-compliant patient intake form was designed to collect renal, cardiovascular, cerebrovascular, renal biopsy and function data along with drug type, indication and frequency of administration.<br><br>RESULTS: In our updated cohort we added 16 total cases from the literature showing signs of renal injury from the patient population receiving VEGFi. In current literature, 46 cases of VEGFi-related renal injury have been documented. To them, we add our 16 cases for a total of 62 cases.<br><br>CONCLUSION: The current database for VEGFi-related nephrotoxicity constitutes the largest case series presented for this condition. This study opens the door for future studies to evaluate what subgroups experience acute kidney injury, proteinuria and hypertension exacerbations. Additionally, we may expand on our database to include timeline markers for symptomatic-correlative VEGFi usage and, in time, predictive measures on a larger scale to correlate comorbidity/drug use with drug effect and mechanism of action.},
}
@article {pmid40754930,
year = {2025},
author = {Dong, Y and Li, Y and Zhou, X and Huang, W and Yang, S and Lin, H and Wei, K and Yao, J and Zuo, H and Zuo, C},
title = {Synergistic Suppression of Choroidal Neovascularization by Cavtratin and Aflibercept via Inhibition of the eNOS Pathway.},
journal = {Current eye research},
volume = {50},
number = {10},
pages = {1054-1063},
doi = {10.1080/02713683.2025.2523916},
pmid = {40754930},
issn = {1460-2202},
mesh = {*Choroidal Neovascularization/drug therapy/metabolism ; Animals ; *Nitric Oxide Synthase Type III/antagonists &amp; inhibitors/metabolism ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Mice ; Humans ; Disease Models, Animal ; Human Umbilical Vein Endothelial Cells ; Mice, Inbred C57BL ; Intravitreal Injections ; *Caveolin 1/metabolism ; Fluorescein Angiography ; Blotting, Western ; Angiogenesis Inhibitors/therapeutic use ; Male ; Signal Transduction ; Cells, Cultured ; Drug Synergism ; },
abstract = {PURPOSE: Choroidal neovascularization (CNV) is a key pathological feature of exudative age-related macular degeneration (AMD), leading to severe vision loss. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies being the first-line treatment for neovascularization, their long-term application faces challenges including treatment insensitivity and drug resistance. This study aims to investigate the role of Caveolin-1 (Cav-1) in CNV pathogenesis and evaluate the therapeutic potential of Cavtratin, a Cav-1 scaffolding domain-targeting peptide, alone and in combination with Aflibercept.<br><br>METHODS: A laser-induced CNV model in aged mice and VEGF-stimulated human umbilical vein endothelial cells (HUVECs) were used to assess Cav-1 expression dynamics and its interaction with endothelial nitric oxide synthase (eNOS). The effects of Cavtratin on angiogenesis were evaluated using tube formation assays, choroidal sprouting assays, and fluorescein angiography. Western blot and immunofluorescence staining were employed to analyze changes in molecular expression, localization, and inflammatory responses. The efficacy of Cavtratin-Aflibercept combination therapy was examined.<br><br>RESULTS: Cav-1 and eNOS were significantly upregulated during CNV progression (p&#x2009;<&#x2009;0.001). Cavtratin effectively inhibited tube formation in HUVECs, suppressed choroidal sprouting ex vivo, and reduced CNV leakage in vivo (p&#x2009;<&#x2009;0.01). Mechanistically, Cavtratin suppressed eNOS phosphorylation and enhanced the anti-angiogenic effects of Aflibercept (p&#x2009;<&#x2009;0.001). The combination therapy led to greater CNV inhibition, reduced inflammation, and allowed for a lower Aflibercept dosage while maintaining therapeutic efficacy.<br><br>CONCLUSION: Cavtratin combined with Aflibercept can effectively enhance anti-angiogenic efficacy and reduce inflammatory responses. Targeting the Cav-1/eNOS axis with Cavtratin provides a novel strategy to complement the limitations of anti-VEGF therapy. The synergistic effects of Cavtratin and Aflibercept suggest a promising approach to overcoming treatment resistance and improving clinical outcomes in CNV management.},
}
@article {pmid40754859,
year = {2025},
author = {Teo, KYC and Ponsioen, TL and Lan, S and OToole, L and Arruabarrena Sanchez, C and Barry, R and Morros, HB and Chung, C and Invernizzi, A and Cheung, GCM and Barthelmes, D and Gillies, MC},
title = {Progression of Loss of Vision From Centre-Involving Macular Atrophy in Eyes Treated for nAMD.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {8},
pages = {925-935},
doi = {10.1111/ceo.14587},
pmid = {40754859},
issn = {1442-9071},
support = {//Australian and New Zealand Eye Foundation/ ; //National Health and Medical Research Council, Australia/ ; //Macula Disease Foundation, Australia/ ; //Walter and Gertrud Siegenthaler Foundation/ ; /SNSF_/Swiss National Science Foundation/Switzerland ; },
mesh = {Humans ; *Visual Acuity/physiology ; Female ; Male ; Aged ; Disease Progression ; Case-Control Studies ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Tomography, Optical Coherence ; Aged, 80 and over ; Registries ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macula Lutea/pathology ; Ranibizumab/therapeutic use ; Fluorescein Angiography ; Retrospective Studies ; Middle Aged ; *Blindness/physiopathology/diagnosis ; Incidence ; Atrophy ; },
abstract = {BACKGROUND: This study aimed to characterise visual acuity (VA) changes in eyes without baseline macular atrophy (MA) that subsequently developed MA during treatment for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A case-control analysis was performed using data from a multicentre real-world AMD registry. We compared VA outcomes in 1998 treatment-na&#xef;ve eyes without MA at baseline and &#x2265;&#x2009;5&#x2009;years of follow-up. Two matched groups (999 eyes each) were analysed: eyes that developed incident MA and those that never did.<br><br>RESULTS: Comparisons were made between two matched groups of 999 eyes each with incident MA and those that never developed it with at least 5&#x2009;years of follow-up. Final VA was best in eyes that never developed MA, followed by eyes that developed extrafoveal and sub-foveal MA (68.9&#x2009;&#xb1;&#x2009;16.7, 67.0&#x2009;&#xb1;&#x2009;16.9 and 52.1&#x2009;&#xb1;&#x2009;23.6 letters, p&#x2009;<&#x2009;0.01). Eyes with incident MA had more inactive disease visits compared to those that never developed MA. Features associated with poor final VA included the presence of sub-foveal MA (odds ratio [OR] [95% confidence interval (CI)] -16.63 [-18.7 to 14.56], p&#x2009;<&#x2009;0.01) and a higher proportion of active visits (per 10%) (OR [95% CI] -0.73 [-1.12 to 0.34], p&#x2009;<&#x2009;0.01). The mean time to lose five letters of vision from first grading of sub-foveal MA was 17.3&#x2009;&#xb1;&#x2009;4.6&#x2009;months.<br><br>CONCLUSION: It is important to achieve disease inactivity in nAMD despite its association with incident MA, as neovascular complications play a significant role in VA loss. The long duration between the incidence of MA and clinically significant loss of vision offers an opportunity for potential interventions against atrophy.},
}
@article {pmid40754855,
year = {2025},
author = {Del Fabbro, S and Jimenez, B and Bianco, L and Antropoli, A and Nunziata, A and Stimola, C and Sarasso, E and Agosta, F and Filippi, M and Arrigo, A and Bandello, F and Battaglia Parodi, M},
title = {Neurovisual rehabilitation of patients with geographic atrophy secondary to age-related macular degeneration with AvDesk system.},
journal = {European journal of ophthalmology},
volume = {35},
number = {6},
pages = {2017-2025},
doi = {10.1177/11206721251349039},
pmid = {40754855},
issn = {1724-6016},
mesh = {Humans ; *Geographic Atrophy/rehabilitation/etiology/physiopathology ; Prospective Studies ; Visual Acuity/physiology ; Male ; Female ; Aged ; Visual Fields/physiology ; *Macular Degeneration/complications/physiopathology ; Aged, 80 and over ; Visual Field Tests ; Tomography, Optical Coherence ; Middle Aged ; Surveys and Questionnaires ; Quality of Life ; },
abstract = {PurposeThe aim of this study is to evaluate the efficacy of neurovisual rehabilitation using the AvDesk training system (Linari Medical, Pisa, Italy) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) in their eye with better visual acuity.MethodsThis study employed a prospective, observational, single-centre case series design. All patients underwent neurovisual rehabilitation using an AvDesk device. The protocol included sessions twice a week for a duration of 3 consecutive weeks. Before and at the end of the protocol, all patients underwent a standardized ophthalmic examination. MAIA microperimeter was used to assess fixation parameters, using bivariate contour ellipse area (BCEA) at both 63% and 95% confidence intervals, and macular sensitivity (MS). Additionally, the NEI-VFQ 25 questionnaire was administered to evaluate the clinical response.Results17 eyes from 17 patients were included in the study. The mean (SD) best-corrected visual acuity (BCVA) at baseline was 0.55 (0.28), improving to 0.39 (0.26) LogMAR (p = 0.0002), after completing the training. The mean (SD) MS did not change, ranging from 8.81 (6.08) dß to 8.60 (5.99) dß (p = 0.30). Following training, both BCEA 63% and 95% values exhibited a modest reduction, although these changes did not reach statistical significance (p > 0.05). Absolute scotomas remained stable (24.41 before treatment vs. 24.65 after treatment; p = 0.83). The NEI-VFQ 25 overall score improved from 55.05 to 62.18 post-treatment (p < 0.01).ConclusionsThe AvDesk training system is an effective tool for neurovisual rehabilitation in AMD patients with GA, yielding improvements in BCVA, fixation stability and quality of life.},
}
@article {pmid40752732,
year = {2025},
author = {Uemura, S and Miki, A and Kishimoto-Kishi, M and Chubachi-Kamimura, A and Nakamura, M},
title = {Two-year treatment outcome of photodynamic therapy combined with anti-vascular endothelial growth factor therapy for pachychoroid neovasculopathy.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {55},
number = {},
pages = {104746},
doi = {10.1016/j.pdpdt.2025.104746},
pmid = {40752732},
issn = {1873-1597},
mesh = {Humans ; *Photochemotherapy/methods ; Female ; Male ; Middle Aged ; Retrospective Studies ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Choroidal Neovascularization/drug therapy ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Photosensitizing Agents/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/drug effects ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Combined Modality Therapy ; Treatment Outcome ; Verteporfin ; },
abstract = {OBJECTIVE: To investigate the two-year treatment outcomes of photodynamic therapy (PDT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with pachychoroid neurovasculopathy (PNV).<br><br>METHODS: A retrospective study was conducted on 22 eyes of 22 treatment-na&#xef;ve patients diagnosed with PNV who underwent combination therapy with PDT and intravitreal anti-VEGF agents (ranibizumab or aflibercept). Patients were followed for at least two years after treatment and evaluated for visual acuity (VA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), presence of recurrent exudative changes, time to recurrence, and additional treatments.<br><br>RESULTS: The study involved 12 male and 10 female patients with a mean age of 64.1 &#xb1; 11.5 years. Baseline VA (0.16&#xb1;0.26) improved significantly at 6 months (0.05 &#xb1; 0.23; P < 0.01), which was maintained until 24 months (0.04 &#xb1; 0.22; P < 0.01). Baseline CRT and SCT (303.1 &#xb1; 105.0 &#x3bc;m and 362.5 &#xb1; 83.8 &#x3bc;m, respectively) showed significant reductions at one month after treatment (184.5 &#xb1; 56.9 &#x3bc;m and 307.7 &#xb1; 94.6 &#x3bc;m; both P < 0.001), which were maintained until 24 months (170.8 &#xb1; 42.9 &#x3bc;m and 286.2 &#xb1; 99.1 &#x3bc;m; both P < 0.001). Recurrence was observed in five eyes (22.7 %) at a mean recurrence interval of 8.5 &#xb1; 3.9 months. The mean number of additional PDT and anti- VEGF treatments was 0.2 &#xb1; 0.4 and 1.9 &#xb1; 4.5, respectively.<br><br>CONCLUSIONS: Combination therapy with PDT and intravitreal anti-VEGF may be effective in improving visual acuity and anatomy in patients with PNV.},
}
@article {pmid40752687,
year = {2025},
author = {Sahu, A and Patel, AR and Shetty, KH and Shah, DO and Willcox, MD and Maulvi, FA and Desai, DT},
title = {Revolutionizing age-related macular degeneration treatment: Advances and future directions in non-invasive retinal drug delivery systems.},
journal = {International journal of pharmaceutics},
volume = {683},
number = {},
pages = {126009},
doi = {10.1016/j.ijpharm.2025.126009},
pmid = {40752687},
issn = {1873-3476},
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Drug Delivery Systems/methods ; Animals ; Retina/metabolism/drug effects ; Nanoparticles ; },
abstract = {Age-related macular degeneration (AMD) remains a leading cause of vision loss worldwide. While anti-VEGF therapies are effective, they rely heavily on invasive intravitreal injections, which carry risks such as infection, retinal detachment, and poor patient compliance. Recent advances in nanotechnology and biomaterials have catalyzed the development of non-invasive drug delivery systems capable of targeting the retina through topical administration. This review explores the complex anatomical and physiological barriers to ocular drug delivery and highlights cutting-edge strategies-such as liposomes, solid lipid nanoparticles, polymeric carriers, micelles, and nanoemulsions-designed to overcome these challenges. Emerging technologies, including drug-eluting contact lenses, microneedle arrays, iontophoretic systems, and hydrogel-based platforms, offer promising avenues for sustained, patient-friendly retinal therapy. However, clinical translation faces significant hurdles related to drug bioavailability, barrier penetration, long-term safety, and regulatory validation. Future perspectives underscore the need for personalized, stimuli-responsive delivery systems and multidisciplinary collaboration to bridge the gap between laboratory innovation and clinical application. By integrating advances in nanomedicine, biomaterials science, and ophthalmology, the next generation of topical ocular therapies is poised to redefine the management of retinal diseases, offering safer, more sustainable, and widely accessible alternatives to intravitreal injections.},
}
@article {pmid40750914,
year = {2025},
author = {Enoch, J and Matthews, D and Ghulakhszian, A and Sekhon, M and Callaghan, T and Crabb, D and Dinah, C and Taylor, D},
title = {Implementing patient and public involvement (PPI) in eye research: reflections from developing a research study on Geographic Atrophy treatment acceptability.},
journal = {Research involvement and engagement},
volume = {11},
number = {1},
pages = {90},
pmid = {40750914},
issn = {2056-7529},
support = {AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; AMR-000001//Apellis Pharmaceuticals/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; EIF 397//National Institute for Health and Care Research/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; HEIF//City, University of London/ ; },
abstract = {BACKGROUND: Awareness of the importance of patient and public involvement (PPI) in ophthalmology research is growing, ensuring studies align with patient priorities and experiences. However, there is limited literature exploring the practicalities and details of how PPI may be conducted within this field. In this case study of PPI within an ophthalmological research project, we aim to provide a transparent, in-depth illustration of how PPI was implemented and helped to shape the Acceptability of Geographic Atrophy INjections (AGAIN) study. The AGAIN study is focused on patients' perspectives regarding the acceptability of new intravitreal (eye) injection treatments for Geographic Atrophy, an advanced form of age-related macular degeneration.<br><br>MAIN TEXT: This commentary explores how PPI was undertaken to shape the design of the two work packages of the AGAIN study. In work package 1, the AGAIN pilot, we worked with a group of patient advisors to design materials for a mixed-methods questionnaire. This questionnaire consisted of Likert-type scale questions, semi-structured interview questions, and an elicitation task considering different hypothetical treatment scenarios. Eight patient advisors provided their input into the design of this questionnaire, and we discuss examples of the concrete changes to the research materials based on the advisors' feedback. In work package 2, we carried out several rounds of consultation with patient advisors to develop a pre-validated quantitative questionnaire on Geographic Atrophy treatment acceptability. This involved using 'think-aloud' techniques to explore the questionnaire's validity, clarity, and comprehensibility. We discuss some of the challenges that may arise when taking on board divergent points of view, and how to maximise comprehensibility without compromising fidelity to a validated questionnaire.<br><br>CONCLUSIONS: Our experience attests to the importance of listening to the insights of patients and those with lived experience in the early stages of designing research, while also ensuring that PPI remains continually integrated throughout the study lifecycle. Our PPI approach evolved in an ad-hoc fashion, and we suggest that given its beneficial impact for our study, PPI should be carefully planned for and adequately resourced in patient-centred ophthalmological research programmes.},
}
@article {pmid40749905,
year = {2025},
author = {Cheruvu, SS and Merugu, S and Malani, M and Kulkarni, O and Nirmal, J},
title = {Hyaluronic acid based light responsive long acting hydrogel for the intraocular delivery of spironolactone.},
journal = {International journal of biological macromolecules},
volume = {321},
number = {Pt 4},
pages = {146451},
doi = {10.1016/j.ijbiomac.2025.146451},
pmid = {40749905},
issn = {1879-0003},
mesh = {*Hyaluronic Acid/chemistry ; *Spironolactone/chemistry/administration &amp; dosage/pharmacology/pharmacokinetics ; Animals ; *Hydrogels/chemistry ; *Light ; Drug Liberation ; *Drug Delivery Systems ; Humans ; Delayed-Action Preparations/chemistry ; Drug Carriers/chemistry ; },
abstract = {Chorio-retinal diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), are responsible for irreversible vision loss worldwide. Non-VEGF pathways, such as the renin-angiotensin-aldosterone system (RAAS), show promise as therapeutic targets for retinal diseases to address the increasing non-responder population to anti-VEGF therapy for DR. Elevated renin levels in DR are linked to retinal angiogenesis and inflammation. Spironolactone (SPL) has demonstrated the potential to reduce angiogenesis. A sustained delivery approach could be beneficial for chronic ocular disorders by delivering the therapeutic dose over a longer duration, thus reducing the frequency of intravitreal administration. Hence, a light responsive methacrylated hyaluronic acid (MEHA) polymer was synthesised and used to develop an in situ gelling depot that provides sustained release of SPL upon UV crosslinking. The in vitro release of SPL from the light responsive in situ depot was seen over 90 days. Furthermore, the in vivo ocular residence studies have demonstrated the depot remaining for >60 days. The SPL-loaded light responsive hydrogel demonstrated in vivo safety and efficacy against DR, further supporting its potential as a long acting drug delivery platform for intravitreally injected drugs with reduced frequency of administration.},
}
@article {pmid40749832,
year = {2025},
author = {Widjaja-Adhi, MAK and Swigris, J and Plau, J and Chung, C and Walczak-Szeffer, A and Jastrzebska, B and Blaner, WS and Golczak, M},
title = {Inactivation of cellular retinol-binding protein 1 protects against bis-retinoid accumulation and light-induced retinal degeneration in mice.},
journal = {The Journal of biological chemistry},
volume = {301},
number = {9},
pages = {110538},
pmid = {40749832},
issn = {1083-351X},
support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 DK122071/DK/NIDDK NIH HHS/United States ; R01 EY023948/EY/NEI NIH HHS/United States ; R01 EY032874/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Mice, Knockout ; *Retinal Degeneration/metabolism/genetics/pathology/etiology ; *Light/adverse effects ; *Retinoids/metabolism ; *Retinol-Binding Proteins, Cellular/genetics/metabolism/antagonists &amp; inhibitors ; *Macular Degeneration/metabolism/genetics/pathology ; ATP-Binding Cassette Transporters/genetics/metabolism ; *Retinaldehyde/metabolism ; Humans ; Stargardt Disease ; Alcohol Oxidoreductases/genetics/metabolism ; Disease Models, Animal ; },
abstract = {Delayed clearance of all-trans-retinal (at-RAL) in photoreceptors is linked to prevalent retinal diseases such as Stargardt disease, rod-cone dystrophies, and age-related macular degeneration. Pharmacological modulation of retinoid metabolism in the eye presents a promising therapeutic strategy, with cellular retinol-binding protein 1 (RBP1) emerging as a potential target. However, it lacks genetic validation as a therapeutic target in an animal model of human disease. Thus, we investigated the effect of the Rbp1 gene inactivation on the phenotype of the Abca4[-/-]/Rdh8[-/-] model of Stargardt disease. Triple knockout (Abca4[-/-]/Rdh8[-/-]/Rbp1[-/-]) mice were protected against light-induced retinal degeneration. RBP1 deficiency also slowed bis-retinoid accumulation in aged animals. Furthermore, pharmacological inhibition of RBP1 alleviated the retinal degeneration phenotype. These findings provide both genetic and pharmacological evidence supporting RBP1 as a promising therapeutic target for retinal degenerative diseases associated with impaired all-trans-retinal clearance.},
}
@article {pmid40746855,
year = {2025},
author = {Duan, MM and Tu, X},
title = {Deep learning-based classification of multiple fundus diseases using ultra-widefield images.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1630667},
pmid = {40746855},
issn = {2296-634X},
abstract = {PURPOSE: This study aimed to develop a hybrid deep learning model for classifying multiple fundus diseases using ultra-widefield (UWF) images, thereby improving diagnostic efficiency and accuracy while providing an auxiliary tool for clinical decision-making.<br><br>METHODS: In this retrospective study, 10,612 UWF fundus images were collected from the JiuJiang No. 1 People's Hospital and the Seventh Affiliated Hospital, Sun Yat-sen University between 2020 and 2025, covering 16 fundus diseases, including normal fundus, nine common eye diseases, and six rare retinal conditions. The model employed DenseNet121 as a feature extractor combined with an XGBoost classifier. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to visualize the model's decision-making process. Performance was evaluated on validation and external test sets using accuracy, recall, precision, F1 score, and AUC-ROC. The model's diagnostic accuracy was also compared with that of junior and intermediate ophthalmologists.<br><br>RESULTS: The model demonstrated exceptional diagnostic performance. For common diseases such as retinal vein occlusion, age-related macular degeneration, and diabetic retinopathy, AUC values exceeded 0.975, with accuracy rates above 0.980. For rare diseases, AUC values were above 0.970, and accuracy rates surpassed 0.998. Grad-CAM visualizations confirmed that the model's focus areas aligned with clinical pathological features. Compared to ophthalmologists, the model achieved significantly higher accuracy across all diagnostic tasks.<br><br>CONCLUSION: The proposed deep learning model can automatically identify and classify multiple ophthalmic diseases using UWF images. It holds promise for enhancing clinical diagnostic efficiency, assisting ophthalmologists in optimizing workflows, and improving patient care quality.},
}
@article {pmid40745881,
year = {2025},
author = {Ndife, TI and Momoh, AJ and Eze, UA and Nwaogwugwu, JO},
title = {Functional Low Vision and Patient Barriers to the Uptake of a Multidisciplinary Low Vision Rehabilitation Service: A Case Study.},
journal = {The Nigerian postgraduate medical journal},
volume = {32},
number = {3},
pages = {233-239},
doi = {10.4103/npmj.npmj_89_25},
pmid = {40745881},
issn = {1117-1936},
mesh = {Humans ; *Vision, Low/rehabilitation/epidemiology/etiology ; Male ; Female ; Cross-Sectional Studies ; Adult ; Middle Aged ; Retrospective Studies ; Aged ; *Health Services Accessibility ; Prevalence ; Visual Acuity ; Young Adult ; *Patient Acceptance of Health Care/statistics &amp; numerical data ; Glaucoma/complications ; },
abstract = {AIMS: To estimate the prevalence, describe causes and prescription needs of functional low vision (FLV) patients, and highlight the barriers these patients encounter to the uptake of multidisciplinary low vision rehabilitation (LVR) service.<br><br>MATERIALS AND METHODS: A mixed study design was adopted. Quantitative analysis consisted of a retrospective and cross-sectional review of 241 (FLV) patients managed at the National Eye Centre, Kaduna. Relevant data extracted from patient records were age, sex, occupation, best-corrected visual acuity, cause of low vision and low vision aids or rehabilitation prescribed. Qualitatively, 45 FLV patients were selected by systematic random sampling. Patient barriers to the uptake of LVR services were elicited through one-on-one interviews.<br><br>RESULTS: The prevalence of FLV was 1.02% (95% confidence interval: 0.98-1.06). The mean age was 44.45 &#xb1; 20 years. One hundred and forty two (59%) were above 40 years old and 60.5% were unemployed. Major causes of FLV were glaucoma (31%), age-related macular degeneration (24%) and retinitis pigmentosa (12%). Prescription needs were magnifiers (29%), non-optical (23%) low vision aids, telescopes (17%), multiple aids (15%) and visual rehabilitation (28%). The uptake of LVRs was 67%. The most common barriers to LVR uptake were the cost of the device (97%), lack of family support (90%) and hesitancy using the device (84%).<br><br>CONCLUSION: FLV was caused by progressively worsening diseases like glaucoma. The major patient barrier to assessing a multidisciplinary LVR service was financial constraint.},
}
@article {pmid40745591,
year = {2025},
author = {Quiroz-Reyes, MA and Quiroz-Gonzalez, EA and Quiroz-Gonzalez, MA and Lima-Gomez, V},
title = {Comparative efficacy of photodynamic therapy (PDT), ranibizumab, aflibercept monotherapy, and combination therapies for polypoidal choroidal vasculopathy: a network meta-analysis of randomized controlled trials.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {440},
pmid = {40745591},
issn = {1471-2415},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Choroid/blood supply ; *Choroid Diseases/drug therapy ; *Choroidal Neovascularization/drug therapy ; Drug Therapy, Combination ; Intravitreal Injections ; *Photochemotherapy/methods ; Photosensitizing Agents/therapeutic use ; Polypoidal Choroidal Vasculopathy ; *Polyps/drug therapy/diagnosis ; Randomized Controlled Trials as Topic ; *Ranibizumab/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Recombinant Fusion Proteins/therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; },
abstract = {PURPOSE: Polypoidal choroidal vasculopathy (PCV) is recognized as a distinct clinical condition characterized by persistent serous leakage, bleeding, and the presence of polypoidal lesions beneath the retinal pigment epithelium (RPE). This systematic review and meta-analysis aimed to evaluate the effectiveness of combination treatments that include antivascular endothelial growth factor (anti-VEGF) agents, such as ranibizumab and aflibercept, along with photodynamic therapy (PDT), in comparison to monotherapy options for managing PCV.<br><br>METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and the Cochrane Library, following the PRISMA guidelines. Eligible studies consisted of treatment-na&#xef;ve patients with PCV receiving anti-VEGF monotherapy, PDT monotherapy, or combination therapies. The key outcomes analyzed included changes in best-corrected visual acuity (BCVA), reduction in central subfield thickness (CSFT), rate of polyp regression, incidence of adverse events, and treatment burden. Statistical analyses were conducted via a random-effects model, and heterogeneity was assessed via the I&#xb2; statistic.<br><br>RESULTS: Fourteen randomized controlled trials (RCTs) involving 1,426 eyes were included. Compared with monotherapies, combination therapies, especially anti-VEGF in conjunction with PDT, showed superior efficacy in improving the BCVA (mean difference [MD]&#x2009;=&#x2009;0.07, 95% CI: 0.06-0.08) and reducing the CSFT (MD = -42.09&#xa0;&#x3bc;m, 95% CI: -59.93 -24.24). The regression rates of polyps were highest in the combination groups, with up to 77.8% achieving complete regression, and fewer anti-VEGF injections were required than monotherapies. Adverse event rates, such as subretinal hemorrhage, remained low across all treatment groups.<br><br>CONCLUSION: Compared with monotherapy, combination therapies using anti-VEGF agents and PDT provide significant visual and anatomical advantages in managing PCV. These treatments are associated with improved efficacy and a reduced treatment burden while maintaining favorable safety profiles. However, further standardization of protocols and evaluation of long-term cost-effectiveness are crucial for improving clinical practice applications.<br><br>TRIAL REGISTRATION: Retrospectively registered.},
}
@article {pmid40745254,
year = {2025},
author = {Cakan-Akdogan, G and Erez, O and Ozer, C and Onal, E and Mert, O and Gullu, S and Arslan, M and Avci, ME and Inan, M and Kalyoncu, S},
title = {Novel anti-VEGF scFv antibodies with superior in vitro and in vivo activities.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {28009},
pmid = {40745254},
issn = {2045-2322},
support = {IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; IBG002//VSY Biotechnology/ ; RareBoost Project #952346//European Commission/ ; 119Z161//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu/ ; 119Z161//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu/ ; 119Z161//T&#xfc;rkiye Bilimsel ve Teknolojik Ara&#x15f;t&#x131;rma Kurumu/ ; },
mesh = {*Single-Chain Antibodies/pharmacology/genetics/immunology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/immunology ; Animals ; Humans ; Zebrafish ; Human Umbilical Vein Endothelial Cells/drug effects ; Ranibizumab/pharmacology ; *Angiogenesis Inhibitors/pharmacology ; Bevacizumab/pharmacology ; Cell Proliferation/drug effects ; Pichia/genetics/metabolism ; Macular Degeneration/drug therapy ; },
abstract = {Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Intravitreal anti-VEGF injection is the gold standard for AMD treatment. Here three novel anti-VEGF single chain variable fragments (scFvs) produced in Pichia pastoris system are reported. First, an scFv was designed based on the variable chain sequence of ranibizumab, then rational mutations were introduced to find the best variant(s). Mutagenesis of two residues that normally reside at the Fab VL- CL resulted in three mutant scFv variants (scFv1, 2, 3) with high affinity to VEGF and good thermal stability. scFv1 and scFv2 outperformed ranibizumab at the HUVEC proliferation inhibition test. The activities of the variants were compared to bevacizumab, ranibizumab and brolucizumab with VEGF bioassay. scFv1 and scFv2 together with brolucizumab performed best, which was seconded by scFv3 and ranibizumab, while all variants performed better than bevacizumab. scFv1 was selected as the lead molecule based on its improved in vivo activity in zebrafish angiogenesis and leaky retinal vasculature models. scFv1 inhibits in vitro angiogenesis and binds selectively to all VEGFA isoforms. The engineered anti-VEGF scFv1, is a promising therapeutic candidate for AMD treatment.},
}
@article {pmid40744710,
year = {2025},
author = {Takeuchi, K and Ueda, T and Imai, M and Fujisaki, M and Tsujimura, M and Tokunaga, Y and Kofuku, Y and Shimada, I},
title = {Two-step target recognition for the competitive inhibition activity of an anti-VEGF aptamer.},
journal = {RNA (New York, N.Y.)},
volume = {31},
number = {10},
pages = {1368-1378},
pmid = {40744710},
issn = {1469-9001},
mesh = {*Aptamers, Nucleotide/chemistry/pharmacology/metabolism/genetics ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/chemistry/metabolism/genetics ; Humans ; Heparin/metabolism/chemistry ; Protein Binding ; Binding, Competitive ; Calcium/metabolism/chemistry ; Binding Sites ; Nucleic Acid Conformation ; *Angiogenesis Inhibitors/pharmacology/chemistry ; },
abstract = {The anti-vascular endothelial growth factor (VEGF) aptamer, t44.27, is a 27-mer RNA that functions as the active component of pegaptanib, an antiangiogenic medicine for neovascular age-related macular degeneration. The t44.27 aptamer is extensively 2'-modified and tightly binds to the heparin-binding domain (HDB) of VEGF165 in a Ca[2+]-dependent manner. However, the molecular mechanism by which the aptamer selectively recognizes VEGF HDB to antagonize its function is poorly understood. We found that t44.27 binds to VEGF HBD in a two-step manner using a different region in the molecule: a transient interaction using a structured region of t44.27 followed by a tight complex formation with a larger interaction surface. Ca[2+] binding stabilizes t44.27 base-pair formation suitable for the initial transient interaction. Meanwhile, the tight complex formation was essential for t44.27 to exert a competitive inhibition of heparin binding to VEGF HBD. These results provide structural insight into how the RNA aptamer specifically interacts with its target molecule to inhibit its activity.},
}
@article {pmid40742530,
year = {2025},
author = {Barth, T and Arnds, J and Mohr, S and Schreiner, L and Helbig, H},
title = {[Smoking and eye diseases].},
journal = {Die Ophthalmologie},
volume = {122},
number = {9},
pages = {753-762},
pmid = {40742530},
issn = {2731-7218},
mesh = {Humans ; *Eye Diseases/etiology/epidemiology/prevention &amp; control ; *Smoking/adverse effects/epidemiology ; Risk Factors ; },
abstract = {Smoking represents a substantial risk factor for various eye diseases due to a variety of harmful mechanisms. Nicotine and other harmful substances in tobacco impair the microcirculation, promote oxidative stress and inflammatory processes. Studies have shown that nicotine abuse increases the risk of cataract development and has an unfavorable effect on the course of glaucoma. Other entities associated with smoking are age-related macular degeneration and ocular vascular occlusions. In addition, nicotine abuse exacerbates ocular surface disorders and has a substantial negative influence on the course of an endocrine orbitopathy. In summary, smoking is an important modifiable risk factor for numerous eye diseases and early prevention and smoking cessation can contribute to reducing these risks.},
}
@article {pmid40742431,
year = {2025},
author = {Eckardt, F and Hafner, M and Lorger, A and Liesenhoff, C and Schiefelbein, J and Herold, TR and Luft, N and Klaas, JE and Schworm, B and Priglinger, SG and Siedlecki, J},
title = {Efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration - 6 month results after completion of the loading phase.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {11},
pages = {3053-3063},
pmid = {40742431},
issn = {1435-702X},
mesh = {Humans ; *Visual Acuity ; Male ; Female ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Aged ; Treatment Outcome ; Fluorescein Angiography/methods ; *Drug Substitution ; Follow-Up Studies ; Time Factors ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Choroid/pathology ; Retrospective Studies ; Recombinant Fusion Proteins/administration &amp; dosage ; Prospective Studies ; Dose-Response Relationship, Drug ; *Macula Lutea/pathology ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors ; Ranibizumab/administration &amp; dosage ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To report the efficacy and durability of switching treatment to faricimab in recalcitrant neovascular age-related macular degeneration (nAMD) at six months after completion of the loading phase (nine months after switching).<br><br>METHODS: Recalcitrant nAMD was defined as persistent fluid despite monthly injections (q4w) or inability to extend treatment intervals beyond six weeks (q6w). The study included patients on a treat &amp; extend regimen for six months after three monthly injections. Primary outcomes were changes in central subfield thickness (CST), subfoveal choroidal thickness (SFCT), visual acuity, and injection interval.<br><br>RESULTS: Nine month-data was available for 56 eyes initially switched to faricimab. At nine months, 51 eyes (91.1%) of 49 patients were maintained on faricimab, while five eyes (8.9%) had been switched back to their older agent. At nine months after switching, median CST was significantly reduced as compared to baseline at switching (332,00 (Q1:295,00; Q3:394,00) to 303,00 (Q1:269,00; Q3:366,00) &#xb5;m; p&#x2009;<&#x2009;0.001). Median SFCT also decreased from 158,00 (Q1:116,00; Q3:219,00) &#xb5;m to 127,00 (Q1:95,00; Q3:196,00) &#xb5;m (p&#x2009;<&#x2009;0.001). The average injection interval was significantly extended from 37.0&#x2009;&#xb1;&#x2009;9.5 days prior to switching to 56.1&#x2009;&#xb1;&#x2009;30.4 days at nine months (p&#x2009;=&#x2009;0.002). Visual acuity was maintained (0.30 (Q1:0.10 Q3:0.50) vs. 0.30 (Q1:0.10 Q3:0.50) logMAR; p&#x2009;=&#x2009;0.07).<br><br>CONCLUSION: In recalcitrant nAMD, faricimab can improve CST and SFCT while maintaining visual acuity. Furthermore, greater durability could be achieved with faricimab at nine months as compared to ranibizumab or aflibercept. Further prospective randomized trials are warranted.},
}
@article {pmid40740189,
year = {2025},
author = {Niu, J and Jin, L and Hu, Y and Wang, Y and Hao, X and Geng, W and Ma, R},
title = {Identification and validation of integrated stress-response-related genes as biomarkers for age-related macular degeneration.},
journal = {Frontiers in molecular biosciences},
volume = {12},
number = {},
pages = {1583237},
pmid = {40740189},
issn = {2296-889X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a prevalent ocular condition associated with aging, serving as a significant contributor to vision loss among middle-aged and older individuals. Studies have shown that AMD and integrated stress response (ISR) are associated with oxidative stress, but no specific molecular mechanisms have been identified. Therefore, this study aimed to identify potential biomarkers for AMD through bioinformatics analysis based on the transcriptome database and integrated stress response related genes (ISR-RGs).<br><br>METHODS: Transcriptomic data GSE76237, GSE247168, and ISR-RGs were sourced from public databases and related literature. The biomarkers associated with AMD were identified by differentially expressed gene (DEG) analysis, intersection of common DEGs, and ISR-RGs machine algorithm. After that, nomograms, GSEA, and immune infiltration analysis were performed for the biomarkers. The effects of transcription factors (TFs) and miRNAs on biomarkers were then explored by constructing a TF-biomarker-miRNA regulatory network. In addition, potential effective drugs of the biomarkers were explored by constructing a biomarker-effective drug interaction network. Finally, we verified the gene expression of the biomarkers by RT-qPCR.<br><br>RESULTS: We obtained 2,567 and 1,454 DEGs in GSE76237 and GSE247168, respectively. The up- and downregulated genes shared in both datasets were intersected with ISR-RGs taken to obtain eight candidate genes. SLFN11 and GRIN1 were identified as common biomarkers for AMD. An analysis of the nomogram model of biomarkers revealed good diagnostic predictive abilities (AUC > 0.7). SLFN11 and GRIN1 were mainly enriched in pathways such as proteasome, lysosome, and neuroactive ligand receptor interaction. In addition, the disease group's monocyte expression was significantly higher than that of the control group in GSE76237 (p < 0.01). We obtained thirteen relevant miRNAs and 27 TFs by prediction, with three shared TFs, and seventeen potentially effective drugs were predicted. RT-qPCR validation showed in AMD patients, and SLFN11 and GRIN1 expression was significantly higher than controls (p < 0.05). Only SLFN11 expression was consistent with the bioinformatics analysis.<br><br>CONCLUSION: SLFN11 and GRIN1 were identified as AMD biomarkers, exhibiting robust diagnostic performance and providing new insights into the condition.},
}
@article {pmid40738389,
year = {2025},
author = {Wang, K and Xie, Y and Lin, Y and Zhu, R and Gao, T and Han, Z and Yang, Z and Jiang, X and Chen, H and Wu, Z and Cai, Y and Zeng, J},
title = {Unveiling the link: aging and its impact on ocular diseases.},
journal = {Experimental eye research},
volume = {259},
number = {},
pages = {110551},
doi = {10.1016/j.exer.2025.110551},
pmid = {40738389},
issn = {1096-0007},
mesh = {Humans ; *Aging/physiology ; *Eye Diseases/physiopathology/metabolism ; },
abstract = {Aging is a process of structural and functional decline that occurs in the body with increasing age. As aging progresses, it weakens the cellular system, leading to dysfunction and metabolic imbalance (mitochondrial metabolism, glucose metabolism, lipid metabolism, and blood and fluid flow changes), which can result in disease. Due to its unique immune and barrier systems, extensive cellular senescence can lead to various eye diseases such as cataracts, glaucoma, age-related macular degeneration (AMD), presbyopia, dry eye disease (DED), corneal disease, vitreous opacity, and diabetic retinopathy (DR). This review discusses the relationship between ocular diseases and aging by analyzing the biological mechanisms of aging and anatomical changes in eye structure and function. Furthermore, we highlight therapeutic advancements for age-related eye diseases, emphasizing pharmacological interventions and innovative delivery systems. Oral antioxidants and anti-VEGF therapies combat oxidative damage and abnormal blood vessel growth, respectively. Lutein provides retinal protection, while lifestyle modifications, including smoking cessation and balanced nutrition, are crucial for mitigating aging effects. Nanoparticle-based therapies offer targeted drug delivery and controlled release, showing promise in treating conditions like AMD. Gene therapy advancements focus on improving mitochondrial function and addressing lipid metabolism disorders. Early screening and timely intervention are essential for effective management. Future research should optimize these therapies for long-term efficacy and safety.},
}
@article {pmid40738331,
year = {2025},
author = {Acharya, B and Momenaei, B and Zhang, Q and Hyman, L and Haller, JA and , },
title = {Disparities in Presentation and Anti-VEGF Therapy Initiation for Neovascular Age-Related Macular Degeneration: An Analysis of the Academy IRIS® Registry (Intelligent Research in Sight).},
journal = {Ophthalmology},
volume = {132},
number = {12},
pages = {1411-1421},
doi = {10.1016/j.ophtha.2025.07.024},
pmid = {40738331},
issn = {1549-4713},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Registries ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology/ethnology ; Middle Aged ; Aged, 80 and over ; *Healthcare Disparities/statistics &amp; numerical data ; *Ranibizumab/administration &amp; dosage/therapeutic use ; United States/epidemiology ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Academies and Institutes ; Receptors, Vascular Endothelial Growth Factor ; },
abstract = {PURPOSE: To investigate disparities in presentation and initiation of anti-VEGF therapy among patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients with nAMD newly diagnosed between October 2016 and October 2021 from the American Academy of Ophthalmology IRIS&#xae; Registry (Intelligent Research in Sight).<br><br>METHODS: Associations between demographic characteristics, presenting visual acuity (VA), and the initiation of anti-VEGF treatment were assessed using multivariable Poisson regression models.<br><br>MAIN OUTCOME MEASURES: Treatment initiation with &#x2265; 1 anti-VEGF injections within 12 months after first presentation with nAMD.<br><br>RESULTS: Among the 918 759 patients with nAMD (61.5% female, 82.3% White), male, Black, and Hispanic patients demonstrated nAMD at younger ages (P < 0.001). Of these, 719 204 patients (78.3%) initiated anti-VEGF treatment within 1 year, with 71.1% of patients (653 340/918 759) receiving the first injection within 1 month. In multivariable regression analysis, Black patients (rate ratio [RR], 0.91; 95% confidence interval [CI], 0.89-0.93; P < 0.001) and Asian patients (RR, 0.95; CI, 0.93-0.97; P < 0.001) were less likely to initiate treatment compared with White patients. Hispanic patients were 4% less likely to initiate treatment than non-Hispanic patients (RR, 0.96; 95% CI, 0.95-0.98; P < 0.001). Patients older than 60 years (vs. those 50-59 years of age) were more likely to initiate treatment (P < 0.001 for all age group comparisons), as were patients from the West (vs. South) region (P < 0.001). Among 701 309 patients with VA data, patients with VA of worse than 20/40 to 20/200 were more likely to initiate treatment (RR, 1.14; 95% CI, 1.12-1.15) than those with 20/20 or better VA, whereas those with hand movements VA (RR, 0.72; 95% CI, 0.69-0.75) and light perception or worse VA (RR, 0.49; 95% CI, 0.44-0.54; all P < 0.001) were less likely to initiate treatment.<br><br>CONCLUSIONS: Over 20% of patients with nAMD did not initiate treatment within 1 year of presentation. Results suggest that lower treatment initiation rates are associated with Black and Asian race, Hispanic ethnicity, age younger than 60 years, and low-vision status. Efforts to improve treatment uptake might prioritize groups with lower initiation rates.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40737650,
year = {2025},
author = {Xu, ZJ and Liu, WW and Xu, F},
title = {THE EFFICACY OF RANIBIZUMAB COMBINED WITH SUBSCLERAL TRABECULAR SURGERY IN THE TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Georgian medical news},
volume = {},
number = {362},
pages = {68-72},
pmid = {40737650},
issn = {1512-0112},
mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Male ; Female ; Aged ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Prospective Studies ; Middle Aged ; *Macular Degeneration/surgery/drug therapy ; Visual Acuity/drug effects ; Intraocular Pressure/drug effects ; Treatment Outcome ; Combined Modality Therapy ; *Trabeculectomy/methods ; Sclera/surgery ; },
abstract = {OBJECTIVE: To investigate the clinical effect of subscleral trabecular surgery combined with intravitreal injection of ranibizumab in the treatment of neovascular age-related macular degeneration (NVG).<br><br>METHODS: 132 patients (132 eyes) with NVG admitted to Jiaozhou Center Hospital of Qingdao from November 2018 to June 2021 were selected. All patients were diagnosed by laboratory examination. The patients were divided into operation group and combined group by clinical randomized prospective study, with 66 cases (66 eyes) in each group. The NVG patients in the operation group were treated with subscleral trabecular surgery, and the combined group was treated with intravitreal injection of ranibizumab on the basis of the operation group.<br><br>RESULTS: The BCAV and intraocular pressure of the two groups were evidently reduced, and the above laboratory indexes of the patients in the combined group were markedly reduced (P<0.05). The overall clinical efficacy of the two groups was better than that of the operation group (P<0.05). The surgical complication rate of the combined group was 9.09% compared with 16.67% of the surgical group (P>0.05).<br><br>CONCLUSION: The clinical effect of subscleral trabecular surgery combined with intravitreal injection of ranibizumab in the treatment of NVG patients is positive, which can more effectively correct the visual acuity and intraocular pressure of patients.},
}
@article {pmid40737361,
year = {2025},
author = {Davis, CN and Carnes, K and Richardson, G and Brandon, W},
title = {Prevalence of Vision-Threatening Ocular Disease Among North Carolina Veterans.},
journal = {Military medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/milmed/usaf381},
pmid = {40737361},
issn = {1930-613X},
abstract = {INTRODUCTION: Prevalence studies on ocular diseases among veterans are limited and underreported. In this retrospective study, we examined the prevalence of vision-threatening ocular diseases among North Carolina veterans. We assessed the prevalence of 6 serious ocular conditions among veterans receiving primary care at the Salisbury Veterans Affairs Health Care System (SVAHCS) in North Carolina to better understand ocular disease prevalence among veterans. Glaucoma, the most common ocular disease in this population, underscores the need for targeted interventions to mitigate vision loss.<br><br>MATERIALS AND METHODS: A retrospective review of medical records from 34,530 veterans enrolled in SVAHCS primary care was conducted. Data collected included demographics such as age, gender, and race. The study focused on 6 vision-threatening diseases: glaucoma, vision-threatening diabetic retinopathy (VTDR), exudative age-related macular degeneration (AMD), retinal vein occlusions (RVO), retinal artery occlusions (RAO), and non-arteritic anterior ischemic optic neuropathy (NAION). Structured Query Language extracted disease frequency, and statistical analysis revealed prevalence rates and socio-demographic patterns.<br><br>RESULTS: The average age of veterans was 69.5 years, with 94% male and 66% White. The most prevalent ocular condition was glaucoma (9%), followed by VTDR (1.3%), exudative AMD (0.9%), RVO (0.8%), RAO (0.4%), and NAION (0.4%). Older male veterans had a disproportionate burden of most ocular conditions. Racial disparities in disease prevalence highlight areas for focused healthcare strategies.<br><br>CONCLUSIONS: This study reveals the significant burden of vision-threatening ocular diseases among North Carolina veterans, with glaucoma being the most prevalent. The findings emphasize the need for targeted screening and personalized interventions to prevent vision loss and address disparities. Further research should explore systemic and behavioral contributors to these trends, guiding evidence-based strategies to improve veterans' ocular health outcomes.},
}
@article {pmid40736870,
year = {2025},
author = {Li, J and Hao, J and Zhu, R and Zhang, J and Wang, Y and Zhang, W and Zhang, Y and Gu, X and Yin, Q and Wu, Z and Yang, L},
title = {Prevalence and Clinical Characteristics of Dark Without Pressure Retinal Changes in a Chinese Hospital-Based Population.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {10},
pages = {2375-2393},
pmid = {40736870},
issn = {2193-8245},
support = {82371064//National Natural Science Foundation of China/ ; 82171059//National Natural Science Foundation of China/ ; BMU2020JI006//Peking University Health Science Center-Michigan Medicine Joint Institute for Translational and Clinical Research Discovery Awards/ ; },
abstract = {INTRODUCTION: This study investigates the clinical characteristics and prevalence of dark without pressure (DWP) retinal changes in a hospital-based Chinese population and evaluates its association with common fundus diseases.<br><br>METHODS: This cross-sectional study analyzed data from 6787 eligible patients recruited from the Ophthalmology Department of Peking University First Hospital between April and July 2023. All participants underwent ultra-wide-field color fundus photography (UWF CFP) for the detection of DWP. Patients were screened by excluding those without UWF CFP images, with blurred images, or who had undergone intraocular surgery, while consolidating duplicate visits. Participants were categorized into diseased (n&#x2009;=&#x2009;3741) and control (n&#x2009;=&#x2009;3046) groups. Prevalence rates were compared between the control group and various disease subgroups (including age-related macular degeneration [AMD], diabetic retinopathy, high myopia, uveitis, retinal hole [RH], retinal detachment [RD], and retinal vein occlusion), as well as across demographic strata, using chi-square tests.<br><br>RESULTS: The overall prevalence of DWP was 21.84% (1481/6787), with a prevalence of 18.55% (565/3046) in the control group. Patients with RH showed the highest prevalence (35.33%, 59/167), whereas those with AMD exhibited the lowest (19.50%, 86/441). There were significant differences in prevalence between the control group and most disease subgroups (all P&#x2009;<&#x2009;0.05), except for AMD (P&#x2009;=&#x2009;0.632). Additionally, DWP prevalence was inversely associated with age (P&#x2009;<&#x2009;0.05) but did not differ by gender (P&#x2009;>&#x2009;0.05). Longitudinal observation revealed diverse DWP patterns, including complete progression, gradual reduction, and bidirectional progression-regression.<br><br>CONCLUSIONS: DWP is highly prevalent in Chinese populations, particularly among younger individuals and patients with retinal disorders. These findings underscore the need for individualized retinal monitoring to prevent unnecessary interventions. Moreover, the dynamic progression of DWP may represent a potential biomarker for retinal disease activity, meriting further mechanistic studies.},
}
@article {pmid40735939,
year = {2025},
author = {Hulleman, JD and Jeon, S and Bali, S and DiCesare, SM and Abbas, A and Daniel, S and Ortega, AJ and Collier, GE and Yang, J and Bhattacharyaa, A and McCoy, MK and Joachimiak, LA and Posner, BA},
title = {Select Azo Compounds Post-translationally Modulate HTRA1 Abundance and Activity Potentially through Interactions at the Trimer Interface.},
journal = {ACS chemical biology},
volume = {20},
number = {8},
pages = {1849-1862},
doi = {10.1021/acschembio.4c00818},
pmid = {40735939},
issn = {1554-8937},
mesh = {*High-Temperature Requirement A Serine Peptidase 1/metabolism/genetics/chemistry ; Humans ; *Azo Compounds/pharmacology/chemistry ; *Protein Processing, Post-Translational/drug effects ; Macular Degeneration/genetics ; Retinal Pigment Epithelium/metabolism ; CRISPR-Cas Systems ; },
abstract = {High-temperature requirement protein A1 (HTRA1) is a secreted serine protease with diverse substrates, including extracellular matrix proteins, proteins involved in amyloid deposition, and growth factors. Accordingly, HTRA1 has been implicated in a variety of neurodegenerative diseases including a leading cause of blindness in the elderly, age-related macular degeneration (AMD). In fact, genomewide association studies have identified that the 10q26 locus that contains HTRA1 confers the strongest genetic risk factor for AMD. A recent study has suggested that AMD-associated risk alleles located in the HTRA1 gene correlate with a significant age-related defect in HTRA1 synthesis in the retinal pigmented epithelium (RPE) within the eye, possibly accounting for AMD susceptibility. Thus, we sought to identify small molecule enhancers of HTRA1 transcription and/or protein abundance using an unbiased high-throughput screening approach. To accomplish this goal, we used CRISPR/Sp.Cas9 engineering to introduce an 11-amino-acid luminescent peptide tag (HiBiT) onto the C-terminus of HTRA1 in immortalized ARPE-19 cells. Editing was very efficient (∼88%), verified by genomic DNA analysis, short interfering RNA (siRNA), and HiBiT blotting. A total of 1920 compounds from two libraries were screened. An azo compound with reported antiamyloidogenic and cardioprotective activity, Chicago Sky Blue 6B (CSB), was identified as an enhancer of endogenous HTRA1 secretion (2.0 ± 0.3 fold) and intracellular levels (1.7 ± 0.2 fold). These results were counter-screened using HiBiT complement factor H (CFH) edited ARPE-19 cells, verified using HiBiT blotting, and were not due to HTRA1 transcriptional changes. Importantly, serine hydrolase activity-based protein profiling (SH-ABPP) demonstrated that CSB does not affect HTRA1's specific activity. However, interestingly, in follow-up studies, Congo Red, another azo compound structurally similar to CSB, also substantially increased intracellular HTRA1 levels (up to 3.6 ± 0.3 fold) but was found to significantly impair HTRA1 enzymatic reactivity (0.45 ± 0.07 fold). Computational modeling of potential azo dye interaction with HTRA1 suggests that CSB and Congo Red can bind to the noncatalytic face of the trimer interface but with different orientation tolerances and interaction energies. These studies identify select azo dyes as HTRA1 chemical probes that may serve as starting points for future HTRA1-centered small molecule therapeutics.},
}
@article {pmid40735363,
year = {2025},
author = {Guo, J and Jiang, Y and Xu, X and Wang, J and Yao, X and Wang, X and Yang, H and Li, MJ and Yan, H},
title = {Deciphering gene-smoking interactions in age-related macular degeneration through cross-biobank genomic integration.},
journal = {Tobacco induced diseases},
volume = {23},
number = {},
pages = {},
pmid = {40735363},
issn = {1617-9625},
abstract = {INTRODUCTION: This study aims to identify genetic loci associated with age-related macular degeneration (AMD) and assess the interaction between genetic susceptibility and smoking history.<br><br>METHODS: A meta-analysis of discovery genome-wide association studies (GWASs), involving a total of 42542 AMD patients and 920322 controls from four large-scale European cohorts, was conducted using METAL, a software tool commonly used for meta-analysis of GWAS. A polygenic risk score (PRS) was derived from the meta-analysis results for 331281 UK Biobank participants. Cox proportional hazards models evaluated interactions between genetic predisposition and smoking history at both PRS and variant levels. Logistic regression models examined plasma complement protein profiles across AMD PRS and smoking status groups.<br><br>RESULTS: We identified two novel risk loci, OCA2 melanosomal transmembrane protein (OCA2) and nitric oxide associated 1 (NOA1). Incorporating the PRS significantly enhanced AMD risk prediction in 331281 UK Biobank participants, with the area under the curve (AUC) increasing from 0.74 to 0.76 (p=2&#xd7;10[-16]). During a mean follow-up of 13.6 years, Cox models revealed significant additive (relative excess risk due to interaction, RERI=0.13; 95% CI: 0.06-0.19; attributable proportion, AP=0.08; 95% CI: 0.04-0.13; synergy index, SI=1.33; 95% CI: 1.13-1.56) and multiplicative interactions (hazard ratio, HR=1.08; 95% CI: 1.03-1.14, p=2.65&#xd7;10[-3]) between PRS and smoking history. Variant-level interactions were prominent at complement factor H (CFH) and complement factor I (CFI) loci. Individuals who have ever smoked and high PRS exhibited dysregulated plasma proteins in the alternative, classical and lectin complement pathways.<br><br>CONCLUSIONS: This study revealed the genetic architecture of AMD and highlighted the synergistic effects of smoking and genetic risk, emphasizing the potential need to integrate genetic assessments into prevention strategies.},
}
@article {pmid40733018,
year = {2025},
author = {Abo Horan, I and Loftsson, T and Sigurdsson, HH},
title = {The Chemical Stability Characterization and Kinetics of Statins in Aqueous Cyclodextrin Ocular Preparations: A Formulation Perspective.},
journal = {Pharmaceutics},
volume = {17},
number = {7},
pages = {},
pmid = {40733018},
issn = {1999-4923},
support = {813440/ERC_/European Research Council/International ; 2410737051//Icelandic Research council/ ; },
abstract = {Background: Topical statin therapy holds promise for ocular diseases, such as age-related macular degeneration, but the effective delivery to the posterior segment is limited by poor aqueous solubility, chemical instability, and ocular barriers. Cyclodextrins (CDs) can enhance statin solubility and stability; however, the behavior of CD-statin complexes in aqueous eye drops-particularly their influence on the equilibrium between the inactive lactone (ring closed) and active hydroxyacid forms (ring open)-remains unclear. This study aimed to (i) investigate how 5% and 10% (w/v) concentrations of selected CDs affect the lactone/acid equilibrium of simvastatin and atorvastatin and (ii) define formulation parameters (statin form, CD type and concentration, and pH range) for stable eye drop development. Methods: Simvastatin or atorvastatin was added to buffered solutions (pH 2.0 to pH 9.5) of RMβCD, HPβCD, γ-CD, or SBEβCD at 0%, 5%, and 10% (w/v), incubated at 23 ± 1 °C, and sampled over time for UPLC quantification of lactone and hydroxyacid forms, and rate constants for the forward and reverse reaction were calculated. Phase solubility studies were also conducted to further characterize equilibrium behavior in aqueous CD systems. Results: The lactone form was most stable at a pH of 4.5, while the hydroxyacid form prevailed at a pH ≥ 7. γ-CD and HPβCD accelerated lactone hydrolysis for both statins, whereas RMβCD exerted a stabilizing effect. Increasing the CD concentration from 5% to 10% provided minimal additional stabilization. Conclusions: These findings highlight that the precise control of the pH, an appropriate cyclodextrin choice, and the selection of the statin form are critical to developing chemically stable eye drops.},
}
@article {pmid40732620,
year = {2025},
author = {Zedadra, A and Salah-Salah, MY and Zedadra, O and Guerrieri, A},
title = {Multi-Modal AI for Multi-Label Retinal Disease Prediction Using OCT and Fundus Images: A Hybrid Approach.},
journal = {Sensors (Basel, Switzerland)},
volume = {25},
number = {14},
pages = {},
pmid = {40732620},
issn = {1424-8220},
support = {Prot. IR0000013429 - Avviso n. 3264 del 28/12/2021.//European Union - NextGenerationEU427 - National Recovery and Resilience Plan (Piano Nazionale di Ripresa e Resilienza, PNRR) - Project:428 "SoBigData.it - Strengthening the Italian RI for Social Mining and Big Data Analytics"/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Fundus Oculi ; Neural Networks, Computer ; *Retinal Diseases/diagnostic imaging/diagnosis ; Diabetic Retinopathy/diagnostic imaging ; Retina/diagnostic imaging ; Macular Degeneration/diagnostic imaging ; },
abstract = {Ocular diseases can significantly affect vision and overall quality of life, with diagnosis often being time-consuming and dependent on expert interpretation. While previous computer-aided diagnostic systems have focused primarily on medical imaging, this paper proposes VisionTrack, a multi-modal AI system for predicting multiple retinal diseases, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), drusen, Central Serous Retinopathy (CSR), and Macular Hole (MH), as well as normal cases. The proposed framework integrates a Convolutional Neural Network (CNN) for image-based feature extraction, a Graph Neural Network (GNN) to model complex relationships among clinical risk factors, and a Large Language Model (LLM) to process patient medical reports. By leveraging diverse data sources, VisionTrack improves prediction accuracy and offers a more comprehensive assessment of retinal health. Experimental results demonstrate the effectiveness of this hybrid system, highlighting its potential for early detection, risk assessment, and personalized ophthalmic care. Experiments were conducted using two publicly available datasets, RetinalOCT and RFMID, which provide diverse retinal imaging modalities: OCT images and fundus images, respectively. The proposed multi-modal AI system demonstrated strong performance in multi-label disease prediction. On the RetinalOCT dataset, the model achieved an accuracy of 0.980, F1-score of 0.979, recall of 0.978, and precision of 0.979. Similarly, on the RFMID dataset, it reached an accuracy of 0.989, F1-score of 0.881, recall of 0.866, and precision of 0.897. These results confirm the robustness, reliability, and generalization capability of the proposed approach across different imaging modalities.},
}
@article {pmid40731132,
year = {2025},
author = {Zhang, A and Wei, TT and Yin, H and Tan, CY and Han, C and Yao, Y and Zhu, L},
title = {Endoplasmic reticulum-mitochondria coupling prompts ZBP1-mediated RPE cell PANoptosis in age-related macular degeneration.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1118},
pmid = {40731132},
issn = {2399-3642},
mesh = {*Endoplasmic Reticulum/metabolism ; *Mitochondria/metabolism ; *Macular Degeneration/metabolism/pathology ; Inflammation/metabolism ; Apoptosis ; Retinal Pigment Epithelium/metabolism/pathology ; *RNA-Binding Proteins/genetics/metabolism ; Humans ; Animals ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; DNA, Mitochondrial/metabolism ; Calcium/metabolism ; Homeostasis ; Multiprotein Complexes/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Mitochondrial Proteins/metabolism ; Acetylglucosamine/metabolism ; Ubiquitination ; Disease Progression ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of central vision impairment among the elderly. Geographic atrophy is a defining characteristic of AMD, but the detailed mechanism for massive loss of retinal pigment epithelium (RPE) cells is not fully understood. In this study, we found that Z-DNA binding protein 1 (ZBP1), a sensor for dsDNA, is able to induce RPE cell PANoptosis. Silencing ZBP1 efficiently alleviates RPE degeneration and AMD symptoms. Mechanistically, mitochondrial permeability transition pore (mPTP) opening stimulated by Ca[2+] overload can trigger the releasing of mtDNA, which leads to ZBP1 activation and PANoptosis. Importantly, our findings reveal a significant role of aberrant formation of mitochondria-associated ER membranes (MAMs) in AMD. MAMs act as conduits for transferring Ca[2+] from the ER to mitochondria through the VDAC1/GRP75/IP3R1 complex. Furthermore, our results indicate that GRP75 O-GlcNAcylation is involved in MAM formation. Genetic suppression of GRP75 attenuates PANoptosis and AMD progression. In summary, our study sheds light on the intricate organelle interplay underlying AMD and presents insights into potential avenues for AMD intervention.},
}
@article {pmid40730279,
year = {2025},
author = {Nguyen, VP and Lee, Y and Park, S and Zheng, M and Wei, Z and Zhang, J and Tran, K and Chen, YE and Yang, D and Paulus, YM},
title = {Multimodal retinal imaging evaluation of macular degeneration persistent disease activity animal model in Watanabe heritable hyperlipidemic rabbits.},
journal = {Experimental eye research},
volume = {259},
number = {},
pages = {110552},
pmid = {40730279},
issn = {1096-0007},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY033000/EY/NEI NIH HHS/United States ; R01 EY034325/EY/NEI NIH HHS/United States ; R42 EY035582/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Rabbits ; Disease Models, Animal ; Tomography, Optical Coherence/methods ; *Multimodal Imaging/methods ; Fluorescein Angiography/methods ; *Choroidal Neovascularization/diagnosis/drug therapy ; *Macular Degeneration/diagnosis/diagnostic imaging ; Angiogenesis Inhibitors/therapeutic use ; *Retina/pathology ; Bevacizumab/therapeutic use ; Photoacoustic Techniques ; *Hyperlipoproteinemia Type II/complications ; *Hyperlipidemias ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; },
abstract = {The Watanabe Heritable Hyperlipidemic (WHHL) rabbit, a model for familial hypercholesterolemia, offers a unique opportunity to study lipid metabolism disorders and their ocular effects. This study employed multimodal imaging, including color fundus photography, fluorescein angiography, indocyanine green angiography, photoacoustic microscopy (PAM), and optical coherence tomography (OCT), to longitudinally assess WHHL rabbit eyes over one year. Given its relevance to persistent disease activity (PDA) in age-related macular degeneration (AMD), WHHL rabbits were evaluated as a potential model for PDA-associated AMD. Choroidal neovascularization (CNV) was induced in WHHL rabbits via subretinal injection of VEGF and Matrigel, followed by bevacizumab (Bev) treatment. A progressive lipid layer developed in the cornea by month 7. Histological analysis revealed significant outer nuclear layer cell loss in WHHL rabbits compared to wild-type (WT) controls. OCT imaging demonstrated increased CNV thickness in WHHL rabbits, consistent with PDA. Bev treatment reduced CNV leakage by 90.13 % in WT rabbits but only 16 % in WHHL rabbits, indicating treatment resistance. PAM at 780 nm effectively distinguished CNV from surrounding microvasculature, while OCT provided detailed retinal imaging. Although rabbits lack a fovea, the WHHL model demonstrates key features of wet AMD, including PDA and reduced anti-VEGF response. Our findings support WHHL rabbits as a promising preclinical model for studying lipid-related retinal diseases, AMD pathophysiology, and treatment resistance, advancing research into novel therapeutic strategies.},
}
@article {pmid40729957,
year = {2025},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Unveiling the P2X7 receptor: Exploring its mechanisms, pathogenic role in ocular diseases, and emerging therapeutic potential.},
journal = {Molecular aspects of medicine},
volume = {105},
number = {},
pages = {101389},
doi = {10.1016/j.mam.2025.101389},
pmid = {40729957},
issn = {1872-9452},
mesh = {Humans ; *Receptors, Purinergic P2X7/metabolism/genetics ; Animals ; *Eye Diseases/metabolism/drug therapy/pathology/etiology ; Purinergic P2X Receptor Antagonists/therapeutic use/pharmacology ; Signal Transduction ; Macular Degeneration/metabolism ; *Retinal Diseases/metabolism ; },
abstract = {Purinergic signaling, mediated by extracellular ATP (eATP) and P2 receptors, plays a vital role in physiological and pathological processes. The P2X7 receptor (P2X7R), a ligand-gated cation channel, is crucial in inflammation, cell death, and immune responses. Widely expressed in retinal cells, P2X7R contributes to visual function regulation and retinal degeneration. This review explores P2X7R involvement in retinal diseases, including age-related macular degeneration (AMD), Behçet's disease (BD), diabetic retinopathy (DR), glaucoma, retinitis pigmentosa (RP), uveitis, Stargardt's disease (STGD), and toxoplasmosis. P2X7R activation drives inflammation, oxidative stress, apoptosis, and immune dysregulation. For instance, it contributes to RPE degeneration in AMD, vascular proliferation in DR, neuroinflammation in glaucoma, and photoreceptor loss in RP. In uveitis, P2X7R enhances Th1 and Th17 responses. Targeting P2X7R with antagonists or modulators holds therapeutic potential, offering strategies to preserve retinal function and prevent vision loss in these debilitating diseases.},
}
@article {pmid40729928,
year = {2025},
author = {Vienne-Jumeau, A and Bousquet, E and Behar-Cohen, F},
title = {Complement system modulation in age-related macular degeneration: navigating failures, building future successes.},
journal = {Current opinion in immunology},
volume = {96},
number = {},
pages = {102616},
doi = {10.1016/j.coi.2025.102616},
pmid = {40729928},
issn = {1879-0372},
mesh = {Humans ; *Macular Degeneration/therapy/immunology/etiology ; *Complement System Proteins/immunology/metabolism ; Animals ; Complement Activation/drug effects ; Biomarkers ; Precision Medicine ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in elderly populations across developed countries. Complement system dysregulation has been implicated in AMD onset and evolution. Complement inhibition therapies have been authorized in the USA as the primary treatment for geographic atrophy, the dry form of AMD. They have shown moderate efficacy in slowing geographic atrophy lesion growth but have not demonstrated improvements in visual function. Challenges remain, including the optimal timing of intervention, delivery routes, safety concerns, the lack of sensitive biomarkers to assess efficacy and guide patient selection, and variability in therapeutic response. Complement modulation represents a promising yet complex therapeutic avenue in AMD. Future success will require earlier intervention, precision medicine approaches integrating genetic and imaging biomarkers, and the exploration of combination or gene-based therapies.},
}
@article {pmid40729752,
year = {2025},
author = {Chen, TL and Tsai, HR and Chang, WC and Lu, JW and Chen, YJ and Lee, YC and Wu, CY},
title = {Risk of age-related macular degeneration in late-onset atopic dermatitis: A multi-database cohort analysis.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004634},
pmid = {40729752},
issn = {1539-2864},
abstract = {PURPOSE: To explore the relationship between atopic dermatitis (AD) and the risk of developing age-related macular degeneration (AMD).<br><br>METHODS: This retrospective cohort study utilized data from two large databases: the US-based TriNetX Research Network (46,018 patients with AD aged &#x2265; 50 years, spanning 2005-2021) and Taiwan's National Health Insurance Research Database (NHIRD; 9,513 patients with AD aged &#x2265; 50 years, spanning 2003-2017). The main outcome was the incidence of AMD. The Cox regression analysis was used to calculate hazard ratios (HRs) for AMD. Additional analyses examined the risk of dry and wet AMD, with stratified assessments based on age, sex, ethnicity, race, and AD activity.<br><br>RESULTS: Adults with AD exhibited a significantly elevated risk of developing AMD in both the TriNetX cohort (HR 1.97; 95% CI 1.78-2.19) and the NHIRD cohort (HR 1.25; 95% CI 1.11-1.41). Individual outcome analyses confirmed a heightened risk for both dry and wet AMD associated with AD. This increased risk was consistent across various groups stratified by demographic factors and AD activity.<br><br>CONCLUSIONS: AD in adulthood is linked to a greater likelihood of developing AMD. These findings underscore the importance of regular funduscopic evaluations and proactive management of AMD in patients with AD.},
}
@article {pmid40729288,
year = {2024},
author = {Bhat, SP and Shipchandler, A and Tokunaga, C},
title = {Social Isolation as a Precipitating Factor for Charles Bonnet Syndrome in a Patient with Mild Visual Deterioration.},
journal = {Reports (MDPI)},
volume = {7},
number = {3},
pages = {},
pmid = {40729288},
issn = {2571-841X},
abstract = {Charles Bonnet Syndrome (CBS) is characterized by complex visual hallucinations in individuals with acute vision loss, typically affecting older adults. Most CBS cases are observed in patients with sudden severe visual impairment; however, there are limited reports of CBS occurring in individuals with mild visual deterioration, particularly when confounded by sensory deprivation and social isolation. Here, we report a case of CBS in a female in her early 80s, who experienced vivid visual hallucinations during a period of prolonged social isolation following a hip surgery. Although symptomatology initially presented as delirium and psychosis, the diagnosis of CBS was confirmed after a neuropsychiatric evaluation and ophthalmologic exam, which showed mild deterioration in the patient's macular degeneration, combined with a social history of reduced independence and increased isolation. The case highlights the lesser-known role of sudden lifestyle changes and reduced cognitive engagement in CBS development in cases of mild visual impairment. It also suggests that cognitive and social stimulation may play a crucial role in CBS management, which has limited reports in the current literature.},
}
@article {pmid40729132,
year = {2025},
author = {, },
title = {Correction: Interpretable multimodal classification for age-related macular degeneration diagnosis.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0329294},
pmid = {40729132},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0311811.].},
}
@article {pmid40727801,
year = {2025},
author = {Lee, KH and Park, B and Jeong, EH and Yoo, GS and Kim, YS and Jin, L and Samadi, AF and Seong, HW and Ryu, JM and Jung, J and Ahn, GH and Kim, JS and Choo, DW and Stewart, JM and Jee, DH and Jahng, WJ},
title = {Phenotypic Drug Discovery Platform by Quantitative High-Throughput Screening Identifies Antiapoptotic Molecules in a Zebrafish Model of Age-Related Macular Degeneration.},
journal = {ACS omega},
volume = {10},
number = {28},
pages = {30467-30488},
pmid = {40727801},
issn = {2470-1343},
abstract = {Age-related macular degeneration (AMD) is a progressive, late-onset, genetic (CFH, HTRA), and environmental (smoking, aging) ocular disease that is a leading cause of blindness affecting more than 200 million people worldwide. New treatments are required for fibrosis, autophagy, and microglia-driven pathologies in AMD patients for personalized medicine approaches, considering that only 10% of AMD patients are treated using the current medicine. The current study examined ninety-one compounds using a phenotypic drug discovery platform in vitro and in vivo to find potential drug candidates that include a new chemical entity (NCE) and extracts from plants such as Diospyros kaki, Achyranthes japonica, and Glycyrrhiza uralensis. The phenotypic drug discovery platform determined mitochondrial function quantitatively by measuring the oxygen consumption rate (OCR) and reactive oxygen species (ROS) of drug-treated cells under oxidative stress in addition to the neuroprotective efficacy test of each candidate. In vitro screening using ARPE-19 cells under oxidative stress identified 18 compounds with significant cytoprotective effects. Among these, JK-14, JK-18, JK-52, and JK-65 demonstrated dose-dependent restoration of cell viability and mitochondrial function, showing a recovered oxygen consumption rate, including basal respiration, ATP-linked respiration, and maximal respiration. In vivo studies used a zebrafish (Danio rerio) model of dry AMD induced by intense blue light exposure. Treatment with natural product candidates, including JK-502, JK-504, JK-505, JK-508, JK-509, JK-514, and JK-520, significantly increased the outer nuclear layer (ONL) thickness, showing a 37% increase compared to blue light-exposed controls, and improved inner retinal layer integrity, including the inner nuclear layer (INL) and inner plexiform layer (IPL). Moreover, the recovery of ganglion cell layer (GCL) nuclei counts further supported the neuroprotective efficacy of these treatments. The current data demonstrate that synthetic small-molecule and natural-product-based formulations can effectively mitigate oxidative stress-induced retinal degeneration. These promising neuroprotectants warrant further investigation as potential therapeutic agents for AMD.},
}
@article {pmid40725833,
year = {2025},
author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S},
title = {Punctate Hyperfluorescence as a Favorable Predictive Factor for Treatment Response Following a Switch to Brolucizumab for Patients with Aflibercept-Refractory Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {14},
pages = {},
pmid = {40725833},
issn = {2077-0383},
abstract = {Background/Objectives: To identify the predictive biomarkers of treatment response following a switch to brolucizumab in patients with aflibercept-refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 47 eyes of 44 patients with nAMD who were switched to brolucizumab; a two-year follow-up was completed for 37 eyes of 34 patients after the switch. The patients were classified into two groups based on the presence (fluid group) or absence (dry group) of retinal fluid at one and two years after switching, and their visual acuity, central retinal thickness, subfoveal choroidal thickness, injection interval, and dry macular rate were evaluated. Results: A dry macula was achieved for approximately 80% of patients at two years after the switch (p < 0.001), and the mean injection interval was significantly extended from 6.4 ± 1.8 weeks to 10.5 ± 2.6 weeks during the same period (p < 0.001). Both the mean central retinal thickness and subfoveal choroidal thickness showed a significant decrease at two years after the switch (p < 0.001 for both). A significantly higher proportion of patients in the Dry group exhibited punctate hyperfluorescence in the fellow eye (p < 0.001), and all patients in the dry group achieved a dry macula at two years. Conclusions: Switching to brolucizumab may be an effective treatment option for patients with aflibercept-refractory nAMD. Punctate hyperfluorescence may serve as a favorable prognostic factor following a switch to brolucizumab.},
}
@article {pmid40725593,
year = {2025},
author = {Palm, C and Zweifel, SA and Gabathuler, F and Cozzi, M and Fasler, K},
title = {Efficacy of Aflibercept 8 mg in Pretreated Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {14},
pages = {},
pmid = {40725593},
issn = {2077-0383},
abstract = {This study aims to evaluate the real-world efficacy and safety of aflibercept 8 mg intravitreal injections (IVTs) in pretreated patients with neovascular age-related macular degeneration (nAMD) throughout the first three IVTs. Background: Established anti-vascular-endothelial-growth-factor (anti-VEGF) therapies positively impact the progression of nAMD but require frequent administration, thus burdening patients and the healthcare system. Pivotal trials of the recently approved aflibercept 8 mg have demonstrated extended dosing intervals with comparable safety to standard treatments. However, real-world data is still scarce. Methods: A retrospective, single-center single-arm analysis was conducted on 22 eyes from 18 pretreated nAMD patients. Eyes were switched from other anti-VEGF agents to aflibercept 8 mg injections continuing a treat-and-extend regimen (no loading dose after switching). Treatment intervals and structural (central subfield thickness (CST); disease activity) and functional (best corrected visual acuity (BCVA)) outcomes were assessed at baseline (date of first aflibercept 8 mg injection) and at follow-up examinations until follow-up 3. Safety data, including intraocular pressure changes, were recorded. Results: Over a median follow-up of 16.6 weeks (IQR 15.1-27.0), patients switched to aflibercept 8 mg showed prolonged intervals between injections (5.5 weeks vs. 7 weeks, p < 0.001, Wilcoxon signed-rank test), reduced disease activity, stable CST, and stable BCVA. One patient experienced transient intraocular pressure elevation, which resolved without intervention. No other adverse events were observed. Conclusions: Treatment with aflibercept 8 mg appears to provide effective disease control with prolonged treatment intervals in switched nAMD patients in routine clinical practice. These findings further indicate the potential for reducing treatment burden.},
}
@article {pmid40725517,
year = {2025},
author = {Hara, C and Fujimoto, S and Fukushima, Y and Sayanagi, K and Nishida, K and Maruyama, K and Sato, S and Maeno, T and Nishida, K},
title = {Initial Response After Switching to Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {14},
pages = {},
pmid = {40725517},
issn = {2077-0383},
abstract = {Objectives: This study aimed to assess the initial anatomical and functional outcomes of switching to aflibercept 8 mg in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-vascular endothelial growth factor (VEGF) therapy. Methods: Patients with nAMD previously treated with anti-VEGF drugs were switched to aflibercept 8 mg. Patients with any exudative changes (subretinal fluid [SRF], intraretinal fluid [IRF] or serous pigment epithelial detachment [sPED]) at the time of the first aflibercept 8 mg injection and whose dosing interval before and after switching did not differ by more than ±7 days were included. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the presence of SRF, IRF, and sPED were evaluated before and after switching to aflibercept 8 mg. Results: A total of 102 eyes from 98 patients were included in the analysis. The drugs used prior to switching were faricimab in five eyes, brolucizumab in six eyes, and aflibercept 2 mg in 91 eyes, with a mean interval of 63.7 ± 20.0 days from the last pre-switch injection and 64.9 ± 20.1 days to the first post-switch visit. The CFT was significantly reduced from 272 ± 85 µm to 246 ± 79 µm (p < 0.0001). The BCVA remained unchanged at 0.27 ± 0.35 logMAR. During switching, SRF, IRF, and sPED were observed in 70, 24, and 38 eyes, respectively. At the post-switch visit, complete resolution of exudative changes was observed in 44% of eyes with SRF, 55% with IRF, and 29% with sPED. No ocular or systemic adverse effects were observed. Conclusions: As an initial response to switching to aflibercept 8 mg in a real-world setting, SRF and IRF completely resolved in approximately half of the patients, and sPED resolved in about 30% of cases.},
}
@article {pmid40725503,
year = {2025},
author = {AlEissa, MM and Alhawsawi, AA and Alonazi, R and Magharbil, E and Aljahdali, A and AlBalawi, HB and Alali, NM and Hameed, S and Abu-Amero, KK and Magliyah, MS},
title = {Advances in Precision Therapeutics and Gene Therapy Applications for Retinal Diseases: Impact and Future Directions.},
journal = {Genes},
volume = {16},
number = {7},
pages = {},
pmid = {40725503},
issn = {2073-4425},
support = {N/A//Internal funding from the Research Department, King Khaled Eye Specialist Hospital, Riyadh and the Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk supported this work./ ; },
mesh = {Humans ; *Genetic Therapy/methods/trends ; *Retinal Diseases/therapy/genetics ; *Precision Medicine/methods/trends ; Macular Degeneration/therapy/genetics ; cis-trans-Isomerases/genetics ; },
abstract = {Gene therapy has emerged as a promising treatment for several eye diseases since it may restore vision and stop blindness. Many eye diseases, including retinitis pigmentosa and macular degeneration, have historically been rather difficult to treat and usually cause permanent vision loss. However, thanks to advances in gene therapy, many disorders can now be effectively targeted and genetically changed, providing a safer, more direct, maybe even curative approach. By introducing, altering, or repairing specific genes inside the eye, gene therapy seeks to fix the defective genes causing these disorders, thereby improving general eye health and visual ability. Voretigene neparvovec is one FDA- and EMA-approved treatment for RPE65 mutations. Retinitis pigmentosa, age-related macular degeneration, X-linked retinoschisis, choroideremia, and Stargardt disease are among the several eye disorders still under clinical trials, and experimental treatment is in progress. As research on gene therapy develops, it opens the path for groundbreaking treatments that could fundamentally change the ophthalmic care scene.},
}
@article {pmid40725453,
year = {2025},
author = {Yoneyama, S and Sakurada, Y and Shijo, T and Fukuda, Y and Kotoda, Y and Kikushima, W and Mabuchi, F and Kashiwagi, K},
title = {Genetic Factors Associated with Intraocular Inflammation After Brolucizumab Administration in Patients with Exudative Age-Related Macular Degeneration.},
journal = {Genes},
volume = {16},
number = {7},
pages = {},
pmid = {40725453},
issn = {2073-4425},
mesh = {Humans ; Male ; Female ; Aged ; *Antibodies, Monoclonal, Humanized/adverse effects/administration &amp; dosage/therapeutic use ; Polymorphism, Single Nucleotide ; *Macular Degeneration/drug therapy/genetics ; Cholesterol Ester Transfer Proteins/genetics ; Aged, 80 and over ; *Inflammation/genetics/chemically induced ; Complement Factor H/genetics ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/genetics ; Genotype ; Genetic Predisposition to Disease ; },
abstract = {Purpose: We aimed to investigate whether genetic variants susceptible to age-related macular degeneration (AMD) are associated with intraocular inflammation after brolucizumab administration in eyes that have exudative AMD. Methods: A total of 206 eyes from 206 patients (156 men/50 women, 74.0 ± 8.4 years; treatment-naïve, 128 [62.1%]; switching, 78 [37.9%]) were included in this study. All patients were treated with intravitreal brolucizumab at least once. The genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH (rs1329428), SKIV2L (rs429608), C3 (rs2241394), cholesteryl ester transfer protein (CETP) (rs3764261), and ADAMTS9 (rs6795375) was performed using TaqMan technology. Results: Out of the 206 patients who were included, 21 eyes from 21 patients (10.2%) exhibited intraocular inflammation (IOI). Four (19.0%) exhibited severe IOI, including retinal vasculitis and/or retinal vascular occlusion, and 17 (81.0%) showed mild IOI. The frequency of the T allele of the CETP gene was significantly lower in patients who developed IOI compared to patients who did not develop IOI (T allele frequency: 9.5% vs. 23.5%, p = 0.036). After adjusting for confounding factors, the T allele remained significantly associated with protection against IOI (p = 0.028, 95% confidence interval: 0.098-0.88). Conclusions: The T allele of the CETP gene, a risk allele for AMD and the protective allele for atherosclerosis, may be associated with protection against IOI after brolucizumab administration in eyes that have exudative AMD.},
}
@article {pmid40725253,
year = {2025},
author = {Dayma, K and Rajanala, K and Upadhyay, A},
title = {Stargardt's Disease: Molecular Pathogenesis and Current Therapeutic Landscape.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
pmid = {40725253},
issn = {1422-0067},
mesh = {Humans ; *Stargardt Disease/therapy/genetics/pathology/metabolism ; Genetic Therapy/methods ; ATP-Binding Cassette Transporters/genetics/metabolism ; Mutation ; Animals ; Oxidative Stress ; },
abstract = {Stargardt's disease (STGD1) is an autosomal recessive juvenile macular degeneration caused by mutations in the ABCA4 gene, impairing clearance of toxic retinoid byproducts in the retinal pigment epithelium (RPE). This leads to lipofuscin accumulation, oxidative stress, photoreceptor degeneration, and central vision loss. Over 1200 pathogenic/likely pathogenic ABCA4 variants highlight the genetic heterogeneity of STGD1, which manifests as progressive central vision loss, with phenotype influenced by deep intronic variants, modifier genes, and environmental factors like light exposure. ABCA4 variants also show variable penetrance and geographical prevalence. With no approved treatment, investigational therapies target different aspects of disease pathology. Small-molecule therapies target vitamin A dimerization (e.g., ALK-001), inhibit lipofuscin accumulation (e.g., soraprazan), or modulate the visual cycle (e.g., emixustat hydrochloride). Gene therapy trials explore ABCA4 supplementation including strategies like RNA exon editing (ACDN-01) and bioengineered ambient light-activated OPSIN. RORA gene therapy (Phase 2/3) addresses oxidative stress, inflammation, lipid metabolism, and complement system dysregulation. Trials like DRAGON (Phase 3, tinlarebant), STARLIGHT (phase 2, bioengineered OPSIN) show promise, but optimizing efficacy remains challenging. With the key problem of establishing genotype-phenotype correlations, the future of STGD1 therapy may rely on approaches targeting oxidative stress, lipid metabolism, inflammation, complement regulation, and genetic repair.},
}
@article {pmid40723297,
year = {2025},
author = {D'Esposito, F and Cappellani, F and Visalli, F and Capobianco, M and Rapisarda, L and Avitabile, A and Cannizzaro, L and Malaguarnera, R and Gagliano, G and Maniaci, A and Lentini, M and Montalbano, G and Zaouali, MA and H'mida, D and Giurdanella, G and Gagliano, C},
title = {Pericytes as Key Players in Retinal Diseases: A Comprehensive Narrative Review.},
journal = {Biology},
volume = {14},
number = {7},
pages = {},
pmid = {40723297},
issn = {2079-7737},
abstract = {Pericytes, specialized mural cells surrounding microvessels, play a crucial role in maintaining vascular homeostasis and function across various organs, including the eye. These versatile cells regulate blood flow, support the integrity of the blood-retinal barrier, and contribute to angiogenesis. Recent advancements in molecular and cellular biology have revealed the heterogeneity of pericytes and their critical involvement in ocular physiology and pathology. This review provides a comprehensive analysis of pericyte functions in ocular health and their implications in diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusion. Pericyte dysfunction is implicated in vascular instability, neurovascular coupling failure, inflammation, and pathological neovascularization, contributing to vision-threatening disorders. The review further explores recent findings on pericyte-targeted therapies, including pharmacological agents, gene therapy, and cell-based approaches, aiming to restore pericyte function and preserve ocular health.},
}
@article {pmid40722794,
year = {2025},
author = {Siqueira, RC and Brandão, CC},
title = {The Role of Cytokines in Degenerative Retinal Diseases: A Comprehensive Review.},
journal = {Biomedicines},
volume = {13},
number = {7},
pages = {},
pmid = {40722794},
issn = {2227-9059},
abstract = {Degenerative retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), are the leading causes of vision loss worldwide. Inflammation plays a crucial role in the pathogenesis of these diseases, with cytokines acting as key mediators of neuroinflammation, vascular dysfunction, and cellular degeneration. This review explores the complex role of cytokines in degenerative retinal diseases, highlighting their involvement in disease progression, cellular interactions, and potential therapeutic strategies. Understanding the cytokine network within the retina may provide novel insights into targeted interventions for these debilitating conditions.},
}
@article {pmid40722572,
year = {2025},
author = {Ardelean, AI and Ardelean, ER and Marginean, A},
title = {Can YOLO Detect Retinal Pathologies? A Step Towards Automated OCT Analysis.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {14},
pages = {},
pmid = {40722572},
issn = {2075-4418},
support = {MySMIS: 334906, and contract number: 390012/28.02.2025//"HUB Rom&#xe2;n de Inteligent&#x103; Artificial&#x103; - HRIA"/ ; },
abstract = {Background: Optical Coherence Tomography has become a common imaging technique that enables a non-invasive and detailed visualization of the retina and allows for the identification of various diseases. Through the advancement of technology, the volume and complexity of OCT data have rendered manual analysis infeasible, creating the need for automated means of detection. Methods: This study investigates the ability of state-of-the-art object detection models, including the latest YOLO versions (from v8 to v12), YOLO-World, YOLOE, and RT-DETR, to accurately detect pathological biomarkers in two retinal OCT datasets. The AROI dataset focuses on fluid detection in Age-related Macular Degeneration, while the OCT5k dataset contains a wide range of retinal pathologies. Results: The experiments performed show that YOLOv12 offers the best balance between detection accuracy and computational efficiency, while YOLOE manages to consistently outperform all other models across both datasets and most classes, particularly in detecting pathologies that cover a smaller area. Conclusions: This work provides a comprehensive benchmark of the capabilities of state-of-the-art object detection for medical applications, specifically for identifying retinal pathologies from OCT scans, offering insights and a starting point for the development of future automated solutions for analysis in a clinical setting.},
}
@article {pmid40722563,
year = {2025},
author = {Ehlers, JP and Yordi, S and Cetin, H and Amine, R and Matar, K and Indurkar, A and Talcott, KE and Kaiser, PK and Khanani, AM and Hu, J and Srivastava, SK},
title = {Differential Visual Outcomes in Neovascular AMD Based on Ellipsoid Zone Integrity and Fluid Presence: Insights from a Phase III Trial.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {14},
pages = {},
pmid = {40722563},
issn = {2075-4418},
support = {n/a//Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA/ ; },
abstract = {Background/Objectives: To investigate the effect of ellipsoid zone (EZ) integrity and retinal fluid on best-corrected visual acuity (BCVA) in neovascular, age-related macular degeneration. Methods: This was a post hoc treatment-agnostic analysis of the phase 3 HAWK trial. Intraretinal fluid (IRF), subretinal fluid (SRF), and ellipsoid zone (EZ) integrity were quantified over 48 weeks. EZ integrity maintenance was defined as EZ-RPE central subfield thickness (CST) >20 µm; partial EZ attenuation was EZ-RPE CST >0 and ≤20 µm; total EZ attenuation was EZ-RPE CST = 0 µm. Results: During treatment, BCVA in eyes with no fluid (66.5 to 70.2 letters) was greater than in eyes with IRF (59.5 to 62.4 letters) but comparable to BCVA in eyes with SRF (64.9 to 68.8 letters). In eyes with no fluid, BCVA was consistently greater in eyes with EZ integrity maintained (73.4 to 78.4 letters) than in eyes with EZ partial attenuation (65.3 to 66.5 letters) or with EZ total attenuation (55.8 to 59.8 letters). Conclusions: Eyes without fluid with EZ preservation achieved the highest overall BCVA, especially when compared to eyes without fluid and a lack of EZ preservation and to eyes with SRF. Achieving a "dry" status with preservation of EZ integrity is important in optimizing visual outcomes.},
}
@article {pmid40721821,
year = {2025},
author = {Tan, JM and Fei, Y and Wang, L and Otero-Marquez, O and Bhuiyan, TR and Arevalo, JF and Lema, GMC and Smith, RT},
title = {Age-related macular degeneration, subretinal drusenoid deposits, and cuticular and calcified drusen in black and hispanic subjects.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {85},
pmid = {40721821},
issn = {2056-9920},
abstract = {BACKGROUND: Subretinal drusenoid deposits (SDDs), cuticular drusen, and calcified drusen have been linked to rapid progression of age-related macular degeneration (AMD). SDDs have also been linked to high-risk vascular diseases (HRVDs). However, SDDs, cuticular drusen, and calcified drusen have not been reported in Black and Hispanic populations. We report that these drusen phenotypes occur in Black and Hispanic AMD patients.<br><br>METHODS: Twenty-three Black and Hispanic AMD subjects were identified in a published cross-sectional study of 200 AMD subjects. Spectral-domain optical coherence tomography, near-infrared reflectance imaging, and lipid profiles were obtained in the parent study. Masked readers assigned subjects into 2 groups: SDDs, present with or without drusen, and drusen only, as in the parent study. Calcified and cuticular drusen were independently identified. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (i.e., aortic stenosis), myocardial defect (i.e., myocardial infarction), and stroke/transient ischemic attack.<br><br>RESULTS: 10/23 subjects were in the SDD group (3 Black and 7 Hispanic subjects), 13 of 23 were in the drusen only group. 4/23 subjects were identified with cuticular drusen (1 Black and 3 Hispanic subjects) and 4/23 subjects were identified with calcified drusen (2 Black and 2 Hispanic Subjects). All subjects had respective phenotypes indistinguishable from that of White subjects. 3/10 SDD subjects had HRVDs.<br><br>CONCLUSIONS: We report, for the first time to our knowledge, that subretinal drusenoid deposits, calcified drusen, and cuticular drusen are present in some AMD patients who identify as Black or Hispanic. A strong association of SDDs with HRVDs was discovered in the parent study. These diseases are known to be over-represented in these under-served populations. SDDs, calcified drusen, and cuticular drusen also confer high risk for progression to advanced AMD. A diligent search for these drusen phenotypes in minority patients with AMD or with HRVDs is thus warranted. Further studies of larger cohorts of Black and Hispanic AMD subjects are needed to better assess associations of these drusen subtypes with life threatening diseases.},
}
@article {pmid40716957,
year = {2025},
author = {Hunt, A and Hashimoto, Y and Young, S and Arnold, J and Game, J and Hooper, C and Field, A and Barry, R and Barthelmes, D and Gillies, M},
title = {Outcomes After Switching to Faricimab in Neovascular Age-Related Macular Degeneration: Data From the Fight Retinal Blindness! Registry.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.14589},
pmid = {40716957},
issn = {1442-9071},
support = {NHMRC 2010-1012//National Health and Medical Research Council/ ; 2007-2009//Royal Australian and New Zealand College of Ophthalmologists/ ; },
abstract = {BACKGROUND: We aimed to describe 1-year outcomes of eyes switched to faricimab from first-generation vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration (nAMD) in routine care.<br><br>METHODS: Multicentre, observational study of 383 eyes tracked in the Fight Retinal Blindness! registry switched to faricimab from aflibercept 2&#x2009;mg, ranibizumab, or bevacizumab between 1st January-1st August 2023 in Australia.<br><br>RESULTS: One-year completion rates were high (335/383 [88%]). The proportion of choroidal neovascular (CNV) lesions graded as inactive increased from 39% at switch to 63% at 12&#x2009;months (p&#x2009;<&#x2009;0.01). Mean visual acuity (95% Confidence Interval) decreased from 70.0 (68.6, 71.5) to 68.4 (66.7, 70.1) logarithm of the minimum angle of resolution letters (both approx. 6/12). Mean treatment intervals increased from 7.2 to 10.5&#x2009;weeks (p&#x2009;<&#x2009;0.01). Eyes with active CNV at switch maintained mean VA -0.5 (-1.7, +0.7) letters; 50% were inactivated at 12&#x2009;months. Eyes with inactive CNV at switch lost -3.5 (-5.0, -1.9) letters; 15% had reactivation at 12&#x2009;months. Switchback occurred in 64/383 eyes (17%), predominantly to aflibercept 2&#x2009;mg, that lost -1.9 letters without interval change at 12&#x2009;months. Adverse outcomes were in keeping with previous reports, with no cases of occlusive retinal vasculitis.<br><br>CONCLUSIONS: We found that faricimab inactivated a significant proportion of CNV lesions that had been active using 1st generation VEGF inhibitors, with a significant extension of the treatment interval. A small reduction in VA occurred in switchers and eyes not switched through the same period.},
}
@article {pmid40716633,
year = {2025},
author = {Xie, J and Xiao, Y and Zhang, Y and Hong, A and Chen, X},
title = {Identification and functional analysis of a novel potent anti-angiogenesis peptide SAIF-B2 derived from shark cartilage.},
journal = {European journal of pharmacology},
volume = {1004},
number = {},
pages = {177961},
doi = {10.1016/j.ejphar.2025.177961},
pmid = {40716633},
issn = {1879-0712},
mesh = {Animals ; Humans ; *Angiogenesis Inhibitors/pharmacology/chemistry/therapeutic use/metabolism ; Zebrafish ; Human Umbilical Vein Endothelial Cells/drug effects ; Sharks ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Molecular Docking Simulation ; *Peptides/pharmacology/chemistry ; *Cartilage/chemistry ; Neovascularization, Physiologic/drug effects ; Neovascularization, Pathologic/drug therapy ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Carcinoma, Hepatocellular/drug therapy/pathology ; Signal Transduction/drug effects ; },
abstract = {Marine-derived bioactive molecules represent promising candidates for lead drug development. Structural optimisation of these lead drugs significantly enhances their suitability as drugs, setting the framework for large-scale manufacturing. We previously identified shark-derived angiogenesis inhibition factor (SAIF), a 33 amino acid peptide from shark cartilage, which has anti-angiogenic activity but has inadequate in vivo stability, thereby limiting clinical translation. In this study, we employed a computational molecular docking-guided truncation strategy to optimise and screen SAIF-B2, a truncated 20 amino acid peptide. SAIF-B2 improved plasma proteolytic stability by 67 % while maintaining strong affinity for vascular endothelial growth factor receptor 2 and vascular endothelial growth factor A. Functionally, SAIF-B2 decreased HUVEC proliferation, migration and tube formation in a dose-dependent manner, resulting in G1/S phase cell cycle arrest. SAIF-B2 markedly suppressed neovascularisation in the chick chorioallantoic membrane assay and zebrafish models. Transcriptomic analysis revealed its anti-angiogenic mechanism, which involves the suppression of VEGF, MAPK, and PI3K-AKT signalling pathways. Notably, SAIF-B2 exhibited potent anti-tumour effects in a hepatocellular carcinoma model and effectively inhibited pathological corneal neovascularisation. These findings establish SAIF-B2 as a superior marine-derived anti-angiogenic peptide with enhanced stability (67 % improvement), smaller molecular weight, and lower production costs than those of its parent molecule. This multi-target therapeutic agent shows significant potential for treating angiogenesis-driven pathologies, including malignancies and macular degeneration, thereby warranting further preclinical development.},
}
@article {pmid40716081,
year = {2025},
author = {Wang, T and Szczepan, M and Gregg, AT and Wang, X and Smith, LEH and Sun, Y},
title = {TREM2-Mediated Myeloid Cells Protect Against Pathological Choroidal Neovascularization.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {14},
pages = {e70881},
pmid = {40716081},
issn = {1530-6860},
support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01EY017017//HHS | NIH | National Eye Institute (NEI)/ ; R01EY030904//HHS | NIH | National Eye Institute (NEI)/ ; R01 EY030140/EY/NEI NIH HHS/United States ; //Massachusetts Lions Eye Research Fund (MLERF)/ ; R01EY029238//HHS | NIH | National Eye Institute (NEI)/ ; //Knights Templar Eye Foundation (KTEF)/ ; //BrightFocus Foundation (BFF)/ ; R01EY030140//HHS | NIH | National Eye Institute (NEI)/ ; },
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Receptors, Immunologic/metabolism/genetics ; *Membrane Glycoproteins/metabolism/genetics ; Mice ; *Myeloid Cells/metabolism/pathology ; Mice, Inbred C57BL ; Microglia/metabolism/pathology ; Macrophages/metabolism/pathology ; Mice, Knockout ; Male ; },
abstract = {Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration, a leading cause of irreversible vision loss in the elderly. While immune dysregulation and myeloid cell activation have been implicated in CNV pathogenesis, the molecular mechanisms by which myeloid subsets influence NV remain incompletely understood. Triggering receptor expressed on myeloid cells 2 (TREM2) is an immunomodulatory receptor enriched in microglia and tissue macrophages, known to play protective roles in retinal and neurodegenerative diseases. However, its function in CNV has not been fully characterized. In this study, we investigated the role of TREM2 in CNV using transcriptomic, genetic, and functional approaches. Single-cell RNA sequencing revealed selective upregulation of Trem2 in activated microglia and macrophages following laser-induced CNV. These findings were validated at the protein level using immunostaining, which confirmed robust TREM2 expression in lesion-associated IBA1[+] myeloid cells. Functionally, Trem2 haploinsufficiency exacerbated CNV lesion size and vascular leakage, indicating a protective role in disease modulation. Transcriptomic profiling demonstrated that Trem2-expressing myeloid cells exhibit distinct angiogenic and inflammasome-related gene signatures, suggesting that TREM2 regulates angiogenesis through modulation of inflammatory pathways. We further examined the functional interaction between TREM2 and suppressor of cytokine signaling 3 (SOCS3), another anti-inflammatory mediator upregulated during CNV. Using compound mutant mice, we showed that Trem2 and SOCS3 function through overlapping but independent anti-angiogenic programs, and their combined deficiency leads to additive worsening of CNV pathology. These findings establish TREM2 as a key regulator of myeloid cell function and angiogenesis in the diseased retina.},
}
@article {pmid40719538,
year = {2025},
author = {Sadeghi, E and Valsecchi, N and Du, K and Davis, E and Schulman, A and DeCicco, JA and Ibrahim, MN and Singh, SR and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Chhablani, J},
title = {Three-Dimensional Choroidal Vessel Analysis in Asymmetric Bilateral Age-Related Macular Degeneration: A Comparison of Active Neovascular AMD and Dry AMD Fellow Eyes.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {9},
pages = {64},
pmid = {40719538},
issn = {1552-5783},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Retrospective Studies ; Aged ; Male ; Cross-Sectional Studies ; *Choroid/blood supply ; Female ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/physiopathology ; Visual Acuity/physiology ; Aged, 80 and over ; *Geographic Atrophy/diagnosis/physiopathology ; *Imaging, Three-Dimensional/methods ; Fluorescein Angiography/methods ; *Choroidal Neovascularization ; Algorithms ; },
abstract = {PURPOSE: To assess choroidal vasculature in bilateral age-related macular degeneration (AMD) patients, with neovascular AMD in one eye and dry AMD in the other, using an innovative three-dimensional (3D) algorithm.<br><br>METHODS: This retrospective cross-sectional study included 30 patients with asymmetric bilateral AMD. All patients underwent clinical exams and swept-source optical coherence tomography using PlexElite-9000 (Carl Zeiss Meditec, Dublin, CA) scans centered on the fovea. The 3D choroidal vasculature was segmented using our validated deep learning algorithm. These 3D maps were divided into five sectors, with the three largest vessels in each sector selected for mean choroidal vessel diameter and inter-vessel distance (IVD) measurements. Volumetric choroidal thickness (ChT) and choroidal vascularity index (CVI) were calculated. Analysis was performed using a linear mixed model.<br><br>RESULTS: This study analyzed 60 eyes from 30 patients, with a mean age of 78.63 &#xb1; 8.01 years. Neovascular AMD eyes had significantly higher mean LogMar visual acuity (0.63 &#xb1; 0.60 vs. 0.20 &#xb1; 0.18, P < 0.001). Neovascular eyes had higher average vessel diameter (253.711 &#xb1; 20.777 vs. 232.641 &#xb1; 28.249 micrometers, P < 0.001), significant in central, temporal, and superior sectors (P < 0.05). IVD was lower in neovascular AMD (209.563 &#xb1; 21.074 vs. 213.867 &#xb1; 30.684&#xa0;&#xb5;m, P = 0.515). Average ChT was lower in neovascular AMD (193.939 &#xb1; 49.627 vs. 198.245 &#xb1; 53.786 &#xb5;m, P = 0.809), significant in the inferior sector (P = 0.011). Additionally, CVI was higher in neovascular AMD (0.365 &#xb1; 0.033 vs. 0.353 &#xb1; 0.035, P = 0.031), particularly in inferior, superior, and central sectors (P < 0.05).<br><br>CONCLUSIONS: Eyes with neovascular AMD demonstrated higher choroidal vessel diameter, ChT, and CVI and decreased IVD compared to dry AMD eyes, possibly related to vessel congestion and inflammation in eyes with active choroidal neovascularization.},
}
@article {pmid40719090,
year = {2025},
author = {Beckers, D and Kretz, F and Glandorf, K and Abdassalam, S and Höhn, F and Amer, M and Breyer, DRH and Beckers, L},
title = {AREDS2 Under Scrutiny: Advocating Unified Regulations.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {7},
pages = {735-740},
doi = {10.1055/a-2611-2310},
pmid = {40719090},
issn = {1439-3999},
mesh = {Germany ; *Macular Degeneration/diet therapy ; Humans ; *Dietary Supplements/standards/analysis ; Ascorbic Acid/analysis ; *Drug Labeling/legislation &amp; jurisprudence/standards ; *Nonprescription Drugs/standards ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of blindness in older adults. Dietary supplements based on the AREDS2 formulation are considered an evidence-based intervention to slow disease progression in intermediate AMD.<br><br>OBJECTIVE: This study aimed to systematically compare the composition of over-the-counter dietary supplements marketed for AMD support with the original AREDS2 formula and to quantify any deviations.<br><br>METHODS: As part of a market analysis, products available in Germany claiming a supportive effect in AMD were identified. The ingredients and dosages declared on the packaging were compared with the reference values used in the AREDS2 study.<br><br>RESULTS: The majority of analysed supplements exhibited substantial deviations from the AREDS2 formulation. On average, the concentrations of vitamin C were 52.3% lower, vitamin E 61.2% lower, and zinc 40.1% lower than the recommended amounts. Only a minority of products matched the reference formulation in both composition and dosage.<br><br>CONCLUSION: There are significant discrepancies in the composition of commercially available AREDS2-based supplements. The implementation of standardised labelling requirements and regulatory guidelines appears necessary to enhance comparability and support evidence-based use in clinical practice.},
}
@article {pmid40718639,
year = {2025},
author = {Lin, X and Zhou, Y and Lv, K and Wu, W and Chen, C},
title = {Nanomedicine-Based Ophthalmic Drug Delivery Systems for the Treatment of Ocular Diseases.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {9221-9249},
pmid = {40718639},
issn = {1178-2013},
mesh = {Humans ; *Nanomedicine/methods ; *Eye Diseases/drug therapy ; *Drug Delivery Systems/methods ; Administration, Ophthalmic ; Animals ; *Ophthalmic Solutions/administration &amp; dosage ; Biological Availability ; Liposomes/chemistry ; },
abstract = {Ocular diseases affect over 2.2 billion people globally, imposing a significant socioeconomic burden, with annual productivity losses estimated at US$411 billion. Conventional drug delivery methods-topical, local injection, and systemic administration-face challenges such as low bioavailability (<5%), rapid clearance, and physiological barriers like the cornea and blood-retinal barrier (BRB). Nanomedicine offers promising solutions by enhancing drug bioavailability, prolonging release, and enabling targeted delivery. This review explores nanomedicine-based ophthalmic drug delivery systems, including organic nanomaterials (eg, liposomes, polymer micelles, dendrimers), inorganic nanomaterials (eg, metal nanoparticles, quantum dots), and biological components (eg, exosomes). These systems improve drug penetration, reduce administration frequency, and minimize toxicity, addressing conditions like dry eye disease, keratitis, glaucoma, uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vascular occlusion (RVO). For instance, Ocular Therapeutix (OTX)-TP, a sustained-release intracanalicular implant combining poly (ethylene glycol)-based hydrogel with travoprost-loaded poly (lactic acid) microspheres, has shown therapeutic efficacy lasting up to three months in the management of glaucoma and ocular hypertension in Phase III clinical trial. Additionally, a liposomal formulation of verteporfin, approved for the treatment of neovascular AMD, administered intravenously and activated by laser photodynamic therapy, demonstrates a durable response, with a marked reduction in treatment frequency from an average of 3.5 sessions in the first year to only 0.1 by the fifth year post-diagnosis. Despite these advantages, challenges such as manufacturing costs, potential toxicity, and limited clinical translation persist. Future advancements in nanomedicine hold potential for personalized, non-invasive ocular therapies, revolutionizing ophthalmology.},
}
@article {pmid40717982,
year = {2025},
author = {Lv, XM and Li, N and Chen, LW and Sun, C},
title = {A comprehensive and systematic review on resveratrol supplementation as a promising candidate for the retinal disease: a focus on mechanisms of action from preclinical studies.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1615910},
pmid = {40717982},
issn = {1663-9812},
abstract = {BACKGROUND: Resveratrol is a natural polyphenolic compound that shows great potential in neuroprotection, anti-inflammation,and antioxidation. Previous studies have demonstrated that resveratrol can effectively treat various animal models of retinal diseases.<br><br>PURPOSE: The aim of the research was to use an animal experimental model to assess the effectiveness of resveratrol in treating retinal-related diseases in various animal models of retinal diseases such as ischemia-reperfusion injury, diabetic retinopathy, glaucoma, chronic ocular hypertension, optic neuritis, age-related macular degeneration, and retinopathy of prematurity. Furthermore, this study aims to reveal the underlying mechanisms of resveratrol related to the treatment of retina-related diseases.<br><br>METHODS: A search was conducted across several databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and OVID. The search time was from the establishment of the database to October 2024 to collect studies on resveratrol intervention in animal models of retinal diseases. The studies included in this paper adopted the SYRCLE's risk of bias tool. Stata 16.0 and RevMan 5.4 software were used to analyze and visualize the results.<br><br>RESULTS: Our meta-analysis comprises 26 studies and 365 animals demonstrates the following effects of resveratrol compared to the control group: a significant increase in the number of retinal ganglion cells (SMD = 3.91, 95% Cl = [2.97, 4.86], p < 0.00001) and superoxide dismutase activity (SMD = 3.14, 95% Cl = [0.96, 5.33], p = 0.005). Moreover, a decrease in malondialdehyde (SMD = -9.29,95% Cl = [-12.84, -5.74], p < 0.00001), reactive oxygen species level (SMD = -4.29,95% Cl = [-6.25, -2.32], p < 0.0001), cyclooxygenase-2 (SMD = -2.66, 95% Cl = [-4.01, -1.30], p =0.0001), tumour necrosis factor-&#x3b1;(SMD = -3.96,95% Cl = [-6.27, -1.65], p = 0.0008) and interleukin-6 (SMD = -3.32,95% Cl = [-4.20, -2.44], p < 0.00001) was observed. The A-wave amplitude and B-wave amplitude showed an increase respectively (MD = 105.92,95% Cl = [58.99, 152.84], p < 0.00001); (MD = 158.00,95% Cl = [86.35, 229.65], p < 0.0001), along with an increase in inner retinal thickness (SMD = 6.33, 95% CI = [5.10, 7.56], p < 0.00001) and total retinal thickness (SMD = 2.70, 95%Cl = [0.77, 4.83], p = 0.01). Subgroup analysis showed that different doses of resveratrol were associated with an increase in the number of RGCs (p < 0.05). Resveratrol improves retinal diseases through multiple mechanisms: i) Neuroprotection: it activates the SIRT1/NF-&#x3ba;B and Nrf2 pathways, inhibits Caspase-3 expression, and promotes the survival of RGCs and ii) Antioxidation: it upregulates SOD activity, reduces the levels of MDA and ROS, and alleviates oxidative damage and iii) Anti-inflammation: it inhibits the COX-2, TNF-&#x3b1;, IL-6, and NF-&#x3ba;B pathways, alleviating the inflammatory response. These mechanisms resulted in enhanced amplitude of A/B waves, improved retinal thickness and visual function.<br><br>CONCLUSION: Resveratrol has neuroprotective, anti-inflammatory and antioxidant effects through multiple mechanisms, thereby reducing retinal damage and maintaining the structure and function of the retina. This provides preclinical support for its possible therapeutic uses in the management of retinal diseases.<br><br>https://www.crd.york.ac.uk/PROSPERO/myprospero.},
}
@article {pmid40715177,
year = {2025},
author = {Lee, H and Jang, H and Chae, JB and Lee, HK and Son, C and Park, CW and Ha, T and Yum, M and Park, S and Hong, SW and Lee, SY and Lyu, J and Lee, S and Lee, DK and Chung, H},
title = {In vivo efficacy of NRL knockdown with cell-penetrating siRNA in retinal degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27176},
pmid = {40715177},
issn = {2045-2322},
support = {RS-2024-00453840//National Research Foundation of Korea/ ; NRF-2019M3A9H1030948//National Research Foundation of Korea/ ; },
mesh = {Animals ; Mice ; *RNA, Small Interfering/genetics/administration &amp; dosage ; *Retinal Degeneration/genetics/therapy/pathology ; *Basic-Leucine Zipper Transcription Factors/genetics/metabolism ; Mice, Inbred C57BL ; *Eye Proteins/genetics/metabolism ; Disease Models, Animal ; Retinal Cone Photoreceptor Cells/metabolism/pathology ; Gene Knockdown Techniques ; Retinal Rod Photoreceptor Cells/metabolism/pathology ; Retinitis Pigmentosa/genetics/pathology ; Electroretinography ; Calcium-Binding Proteins ; },
abstract = {Retinal degenerative diseases, such as retinitis pigmentosa (RP) and age‑related macular degeneration (AMD), lead to progressive vision loss through photoreceptor degeneration; RP begins with the gradual loss of peripheral rods, whereas AMD causes central‑vision loss mainly because macular cones and parafoveal rods degenerate. The neural retina leucine zipper (NRL) directs rod photoreceptor differentiation, and its disruption has been linked to upregulated cone-specific markers in rods. This study investigates the therapeutic potential of a cell-penetrating asymmetric small interfering RNA targeting NRL (cp-asiNRL) to induce rod-to-cone conversion and mitigate retinal degeneration. cp-asiNRL was administered intravitreally to C57BL/6J wild-type (WT), neovascular AMD (nAMD), and RP (Rho[P23H/+]) mouse models. Subsequent analyses included cone marker expression levels and electroretinographic evaluations, and single-cell RNA sequencing. Administration of cp-asiNRL suppressed NRL expression, increased cone marker expression, and improved retinal function in both WT and nAMD models. In RP mice, cone marker expression was also elevated, although functional improvements were comparatively modest, likely reflecting the advanced disease stage. Single-cell RNA sequencing revealed a rod-to-cone-like transdifferentiation, suggesting that cp-asiNRL-mediated NRL knockdown partially preserved photoreceptor integrity. cp-asiNRL-mediated NRL silencing shows considerable promise as a therapeutic intervention for retinal degenerative conditions. By promoting rod-to-cone transdifferentiation and supporting photoreceptor survival, this approach may offer a novel strategy for vision preservation.},
}
@article {pmid40713972,
year = {2025},
author = {Yang, W and Gao, R and Chen, L and Li, S},
title = {CXCR4[+] monocytes promote neovascularization in wet age-related macular degeneration.},
journal = {Experimental eye research},
volume = {259},
number = {},
pages = {110550},
doi = {10.1016/j.exer.2025.110550},
pmid = {40713972},
issn = {1096-0007},
mesh = {*Receptors, CXCR4/metabolism ; *Monocytes/metabolism/pathology ; *Wet Macular Degeneration/metabolism/pathology/genetics ; Humans ; *Choroidal Neovascularization/metabolism/pathology ; Animals ; Mice ; Signal Transduction ; Immunohistochemistry ; Mice, Inbred C57BL ; Disease Models, Animal ; Endothelial Cells/metabolism/pathology ; Cell Differentiation ; Male ; },
abstract = {Wet age-related macular degeneration (wAMD) pathogenesis is primarily driven by choroidal neovascularization (CNV) mediated through intricate angiogenesis-inflammation crosstalk. While chemokine signaling has emerged as a promising therapeutic target, the specific cellular mediators orchestrating this process remain poorly defined. In this study, we employed an integrative approach combining bulk RNA sequencing, single-cell transcriptomics, multiplex immunohistochemistry (mIHC), and in vivo models to systematically elucidate the pivotal role of chemokine signaling in wAMD-associated angiogenesis and identify critical monocyte subsets involved in neovascularization. Our comprehensive analysis revealed MMP2+ endothelial cells (ECs) as a distinct cellular subset demonstrating dual angiogenic and stem-like properties, originating from a dysregulated endothelial differentiation pathway. Furthermore, we identified CXCR4+ monocytes as crucial mediators of pathological angiogenesis, with their activity likely modulated through CXCL12-CXCR4 chemokine axis interactions with MMP2+ ECs. Through transcription factor network analysis, we established RUNX3 as a master regulatory element governing pro-angiogenic monocyte differentiation, providing novel mechanistic insights into monocyte-driven angiogenesis in wAMD pathogenesis. These findings collectively establish MMP2+ ECs and CXCR4+ monocyte signaling as central pathogenic drivers in wAMD. Our results propose that therapeutic targeting of RUNX3-mediated chemokine signaling could synergize effectively with current anti-VEGF treatment paradigms.},
}
@article {pmid40713962,
year = {2025},
author = {Liu, X and Liu, G and Zhang, Q},
title = {Re: Brown et al.: MERLIN: Two-year results of brolucizumab in participants with neovascular age-related macular degeneration and persistent retinal fluid. (Ophthalmology. 2025;132:131-140).},
journal = {Ophthalmology},
volume = {132},
number = {10},
pages = {e169},
doi = {10.1016/j.ophtha.2025.06.008},
pmid = {40713962},
issn = {1549-4713},
}
@article {pmid40712801,
year = {2025},
author = {Carlà, MM and Mottola, F and Cusato, M and Oreste, G and Campaniello, G and Mateo, C and Couturier, A and Philippakis, E and Caporossi, T and Rizzo, S},
title = {Vitreoretinal interface abnormalities in age-related macular degeneration: Prevalence, pathophysiology, and reciprocal influence.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.07.010},
pmid = {40712801},
issn = {1879-3304},
abstract = {Age-related macular degeneration (AMD) represents a leading cause of vision loss worldwide, while vitreoretinal interface (VRI) abnormalities constitute a dynamic boundary where posterior vitreous interacts with the retinal surface. We explore the intricate relationship between VRI abnormalities and AMD, examining prevalence, underlying pathophysiological mechanisms, and their reciprocal influence on disease development, progression, and treatment outcomes. Evidence suggests a higher prevalence of vitreomacular adhesion in exudative versus nonexudative AMD, while complete posterior vitreous detachment may exert protective effects against AMD progression. Tractional forces, inflammatory mediators, and structural disruption associated with VRI abnormalities may promote AMD progression and confound assessment of anti-vascular endothelial growth factor therapy efficacy. Recent findings underscore that epiretinal membranes might act as physical barriers reducing drug penetration, while VMT/VMA can alter macular morphology, potentially mimicking or obscuring therapeutic response. Surgical management of VRI abnormalities in AMD can achieve anatomical success, though visual outcomes may be limited by underlying macular pathology. Early detection and characterization of VRI abnormalities in AMD patients could improve risk stratification, guide treatment timing, and potentially lead to novel preventive strategies, highlighting the importance of comprehensive evaluation and individualized management approaches for optimizing outcomes in this complex patient population.},
}
@article {pmid40712125,
year = {2025},
author = {Heinke, A and Agnihotri, A and Nagel, ID and Kalaw, FGP and Mehta, NN and Sherif Morsy, M and Cheng, L and Uwe-Bartsch, D and Freeman, WR},
title = {OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ANALYSIS OF COHORT WITH PERIPAPILLARY CHOROIDAL NEOVASCULARIZATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {2297-2302},
doi = {10.1097/IAE.0000000000004626},
pmid = {40712125},
issn = {1539-2864},
support = {R01EY016323/GF/NIH HHS/United States ; 5R01EY033847/GF/NIH HHS/United States ; OT2OD032644/GF/NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Retrospective Studies ; Male ; Female ; Aged ; *Choroidal Neovascularization/drug therapy/diagnosis/etiology ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; Fundus Oculi ; Ranibizumab/therapeutic use/administration &amp; dosage ; *Choroid/blood supply ; Optic Disk ; *Wet Macular Degeneration/drug therapy/complications/diagnosis ; Bevacizumab/therapeutic use ; },
abstract = {PURPOSE: Although many studies have analyzed macular choroidal neovascularization (CNV) using optical coherence tomography angiography, few have focused on peripapillary CNV, which comprises approximately 10% of CNV cases. This study examines optical coherence tomography angiography vessel changes in patients with treated and untreated peripapillary CNV to better understand disease progression.<br><br>METHODS: Nineteen eyes with peripapillary CNV secondary to neovascular age-related macular degeneration were retrospectively analyzed. Treated eyes (n = 13) received anti-VEGF injections after a modified pro re nata regimen, whereas untreated eyes (n = 6) without macular involvement were closely observed. Median follow-up was 11.9 months (treated) and 8 months (untreated). High-quality optical coherence tomography angiography scans centered on the CNV lesions were selected and analyzed using validated software (ImageJ and AngioTool).<br><br>RESULTS: Treated eyes showed significant reductions in CNV lesion size, vessel density, and lacunarity after anti-VEGF therapy (ImageJ: P < 0.001; AngioTool: P = 0.0004). Untreated eyes exhibited significant lesion enlargement (ImageJ: P = 0.0356; AngioTool: P = 0.0013). None of the patients in the untreated group developed macular exudation during the study.<br><br>CONCLUSION: Peripapillary CNV without macular involvement may be considered for short-term observation in selected cases, as these lesions appeared indolent and stable over the limited follow-up period in our cohort. The vessels in optical coherence tomography angiography in the treated group showed regression in size after anti-VEGF therapy. These findings will potentially help clinicians better understand this entity.},
}
@article {pmid40712124,
year = {2025},
author = {McLaughlin, SA and Davila, N and Shields, C and Bineshfar, N and Banaee, T and Williams, BK},
title = {IMPACT OF GLP-1 RECEPTOR AGONISTS FOR TYPE 2 DIABETES MELLITUS ON THE DEVELOPMENT AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {2241-2251},
doi = {10.1097/IAE.0000000000004616},
pmid = {40712124},
issn = {1539-2864},
support = {UL1 TR001439/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/drug therapy/complications ; Retrospective Studies ; Male ; Female ; *Glucagon-Like Peptide-1 Receptor Agonists ; Disease Progression ; Aged ; *Hypoglycemic Agents/therapeutic use ; Incidence ; Middle Aged ; *Macular Degeneration/epidemiology/prevention &amp; control/etiology ; Follow-Up Studies ; Aged, 80 and over ; },
abstract = {PURPOSE: To evaluate whether GLP-1 receptor agonist (GLP-1RA) therapy reduces the risk of age-related macular degeneration (AMD) in type 2 diabetes mellitus (T2DM) patients.<br><br>METHODS: A retrospective cohort study using a global health research network matched T2DM patients on GLP-1RA versus non-GLP-1RA therapy. AMD incidence was determined over the first 1 to 10 years of treatment. Patients with baseline early or intermediate nonexudative AMD were also matched and assessed for progression to advanced AMD. Measures of association analysis was used to calculate risk, risk difference, and risk ratio.<br><br>RESULTS: Among 600,816 matched patients without a history of AMD, GLP-1RA users had a 15% relative risk reduction in incidence of nonexudative AMD (RR, 0.851; 95% CI, 0.801-0.905; P < 0.0001) versus those who received alternative therapy. These patients also had a 20% relative risk reduction in incidence of exudative AMD (RR, 0.80; 95% CI, 0.808-0.989; P < 0.0001). To assess progression, 4,450 patients with early or intermediate AMD were matched between the cohorts. GLP-1RA use was associated with 29% relative risk reduction in progression to advanced nonexudative AMD (RR, 0.715; 95% CI, 0.529-0.967; P = 0.028) and a 27% relative risk reduction in progression to exudative AMD (RR, 0.729; 95% CI, 0.601-0.883; P = 0.001).<br><br>CONCLUSION: GLP-1RA use may reduce both the risk and progression of AMD and progression of early and intermediate AMD to advanced AMD in adults with T2DM. GLP-1RAs have been shown to promote neuronal survival and reduce inflammation, which may provide a pathophysiological explanation of the potential beneficial role of GLP-1RAs.},
}
@article {pmid40711716,
year = {2025},
author = {Seber, E and Yaylacı, S},
title = {Sustained Drug Delivery Systems for Age-Related Macular Degeneration: Advancements, Challenges, and Future Perspectives.},
journal = {Advances in experimental medicine and biology},
volume = {1499},
number = {},
pages = {71-86},
pmid = {40711716},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Drug Delivery Systems/trends/methods ; Delayed-Action Preparations ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Angiogenesis Inhibitors/administration &amp; dosage ; Animals ; Hydrogels/chemistry ; Intravitreal Injections ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly and remains a major public health challenge due to its chronic progression and high recurrence rate. Current standard treatment relies heavily on repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents, which impose significant burdens on patients and healthcare systems. In recent years, sustained-release drug delivery systems (SR-DDS) have emerged as promising alternatives to overcome the limitations of frequent injections and to improve therapeutic outcomes in AMD.This chapter explores the rationale, mechanisms, and current advancements in hydrogel-based platforms and implantable devices designed for the long-term delivery of anti-VEGF agents. We provide a comparative analysis of these two delivery modalities, focusing on their materials, biocompatibility, release kinetics, clinical utility, and translational potential. Furthermore, we discuss the critical role of SR-DDS in supporting personalized medicine through patient-specific dosing strategies and their ability to maintain therapeutic drug levels with minimal invasiveness.Challenges in the development and regulatory approval of SR-DDS, including manufacturing complexity, long-term safety, and economic viability, are also addressed. Finally, we highlight emerging trends in biomaterials science, precision engineering, and combination therapy strategies that may shape the next generation of drug delivery platforms for AMD.Together, these insights underscore the transformative potential of SR-DDS in redefining the clinical management of AMD by offering sustained, localized, and patient-tailored therapeutic delivery.},
}
@article {pmid40711662,
year = {2025},
author = {Björnestedt, R and Waters, S and Paišytė, A and Furlan, F and Wanner, C},
title = {Evaluation of XSB-001 (Ranibizumab Biosimilar) Physicochemical and Biological Stability in Prepared Syringes for Intravitreal Injection.},
journal = {Advances in therapy},
volume = {42},
number = {9},
pages = {4597-4610},
pmid = {40711662},
issn = {1865-8652},
mesh = {Drug Stability ; Syringes ; *Ranibizumab/chemistry/administration &amp; dosage ; Intravitreal Injections ; *Biosimilar Pharmaceuticals/chemistry/administration &amp; dosage ; Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/chemistry ; Drug Storage ; Chromatography, High Pressure Liquid ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {INTRODUCTION: Vascular endothelial growth factor A (VEGF-A) is a key driver of neovascularization and vascular permeability in retinal diseases such as neovascular age-related macular degeneration and diabetic macular edema. XSB-001 (Ximluci[®]), a ranibizumab biosimilar has demonstrated equivalent safety, efficacy, and biological activity to reference ranibizumab, supporting its use in these indications.<br><br>METHODS: This study evaluates the extended physicochemical and biological stability of XSB-001 under real-world handling conditions for 30&#xa0;days. XSB-001 was stored at 5&#x2009;&#xb1;&#x2009;3&#xa0;&#xb0;C in vials and prepared into two syringe types. Samples were maintained under monitored conditions for 30&#xa0;days, with a subset exposed to room temperature, humidity and indoor lighting or protected from light for 48&#xa0;h.<br><br>RESULTS: Across all test conditions, XSB-001 maintained expected liquid physical state, clarity, and color within specification limits, besides charge variants. High monomer purity (99.6%), high molecular weight species (0.4%) and low molecular weight species (<&#x2009;0.35%) were observed, satisfying all required criteria. Size exclusion-high-performance liquid chromatography (SE-HPLC) analysis confirmed monomer content at 99.6%, surpassing the&#x2009;&#x2265;&#x2009;99.0% requirement. Reverse-phase high-performance liquid chromatography (RP-HPLC) showed consistent main peak purity of 97.3%, exceeding the&#x2009;&#x2265;&#x2009;97.0% criterion. Strong cation exchange high-performance liquid chromatography (SCX-HPLC) recorded main peak values between 96.5 and 96.6%, meeting the&#x2009;&#x2265;&#x2009;96.5% threshold. Acidic (1.7%) and basic species (1.6-1.7%) were consistently within specification limits (&#x2264;&#x2009;2.5%). Sub-visible particulate analysis indicated particle counts within acceptable limits. Protein concentration was stable across storage conditions, ranging from 9.9 to 10.4&#xa0;mg/ml.<br><br>CONCLUSION: These findings support the extended stability of XBS-001 stored in unopened vials and subsequently prepared syringes (and independent of syringe type), optimizing patient care and treatment management efficiency.},
}
@article {pmid40711396,
year = {2025},
author = {Chong, DD and Yue, SC and Raynor, JL and Murray, I and Chuchta, TG and Markle, JC and Shaia, JK and Singh, RP and Talcott, KE},
title = {Estimated Five-year Risk of Systemic Cardiovascular Events With Anti-VEGF Injections in Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {10},
pages = {587-592},
doi = {10.3928/23258160-20250702-01},
pmid = {40711396},
issn = {2325-8179},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Intravitreal Injections ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis/complications ; Middle Aged ; *Ranibizumab/administration &amp; dosage/adverse effects ; Aged, 80 and over ; Follow-Up Studies ; *Cardiovascular Diseases/epidemiology/etiology ; Risk Factors ; *Bevacizumab/administration &amp; dosage/adverse effects ; Risk Assessment/methods ; Time Factors ; Incidence ; *Myocardial Infarction/epidemiology ; },
abstract = {BACKGROUND AND OBJECTIVE: To assess 5-year risk for stroke, myocardial infarction (MI), and mortality in patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor (anti-VEGF) injections compared to patients with geographic atrophy (GA).<br><br>PATIENTS AND METHODS: A retrospective cohort study was conducted involving 2,923 patients aged &#x2265; 50 years, diagnosed with nAMD or GA prior to 2019. There were two cohorts: those receiving anti-VEGF for nAMD and those with GA. A 1:1 greedy matching algorithm matched demographics, comorbidities, and medications. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for primary outcomes.<br><br>RESULTS: After matching, there were 1,065 patients in each cohort. No significant differences were observed in risks for ischemic stroke (RR = 1.24, 95% CI [0.91, 1.70]), hemorrhagic stroke (RR = 0.95, [0.52, 1.92]), MI (RR = 0.98, [0.70, 1.39]), or mortality (RR = 1.00, [0.83, 1.19]).<br><br>CONCLUSION: Our findings suggest anti-VEGF therapy for nAMD does not increase the risk of stroke, MI, or mortality compared to patients with GA.},
}
@article {pmid40709695,
year = {2025},
author = {Qi, Z and Qi, J and Zhang, Y and Wang, Y and Feng, Y and Yang, Z and Wang, Y and Shu, W and Guo, D and Kang, C and Zhang, K and Lu, Y and Wan, J and Zhu, X},
title = {Plasma Metabolic Profile with Machine Learning Reveals Distinct Diagnostic and Biological Signatures for Pathologic Myopia.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {39},
pages = {e05861},
pmid = {40709695},
issn = {2198-3844},
support = {2022YFC2502800//National Key Research and Development Program of China/ ; 2024YFE0102200//National Key Research and Development Program of China/ ; 22474040//National Natural Science Foundation of China/ ; 82271069//National Natural Science Foundation of China/ ; 82371040//National Natural Science Foundation of China/ ; 82122017//National Natural Science Foundation of China/ ; 81870642//National Natural Science Foundation of China/ ; 81970780//National Natural Science Foundation of China/ ; 81470613//National Natural Science Foundation of China/ ; 81670835//National Natural Science Foundation of China/ ; 23Y11909800//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; 2024ZZ1025//Outstanding Youth Medical Talents of Shanghai "Rising Stars of Medical Talents" Youth Development Program, Shanghai Municipal Health Commission Project/ ; 20244Z0015//Outstanding Youth Medical Talents of Shanghai "Rising Stars of Medical Talents" Youth Development Program, Shanghai Municipal Health Commission Project/ ; //Fundamental Research Funds for the Central Universities/ ; },
mesh = {Humans ; *Machine Learning ; *Biomarkers/blood ; *Myopia, Degenerative/diagnosis/blood/metabolism ; *Metabolome ; Male ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Oxidative Stress ; Female ; Middle Aged ; Metabolomics/methods ; },
abstract = {Pathologic myopia (PM), characterized by serious myopic macular degeneration (MMD), is a detrimental subtype of high myopia (HM) and has become one of the leading causes of blindness worldwide. In this concern, precise and high-throughput molecular diagnosis and further pathologic insights are urgently needed. Here, through the combined strategy of nanoparticle-enhanced laser desorption/ionization mass spectrometry-based rapid metabolic analysis (<30 s) and machine learning, a precise molecular diagnostic approach of PM (HM with MMD grade ≥ 2) is proposed, which achieves areas under the curve of 0.874 and 0.889 for diagnosing PM and early-stage PM, respectively. Further, the biomarkers indicate the PM-associated systemic metabolic reprogramming of amino acid and lipid metabolism, which may mediate dysfunctional oxidative stress, inflammation, hormone/neurotransmitter systems, and energy metabolism. Notably, MMD grade 4, featuring characteristic macula atrophy, exhibits specificity in this metabolic reprogramming. Of these biomarkers, azelaic acid shows a significant protective effect in the ARPE-19 cells under abnormal oxidative stress, which may be involved in PM development as a key antioxidative active metabolite. This work will contribute to PM molecular diagnosis and pathology exploration.},
}
@article {pmid40707687,
year = {2025},
author = {Shin, S and Ryoo, JH},
title = {Combined exposure to three heavy metals and the risk of age-related macular degeneration in the Korean population.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {27016},
pmid = {40707687},
issn = {2045-2322},
support = {RS-2024-00509118//Ministry of Health and Welfare, Ministry of Science and ICT, Ministry of Trade, Industry and Energy, and Korea Disease Control and Prevention Agency/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology/chemically induced/etiology ; Republic of Korea/epidemiology ; Male ; Female ; Middle Aged ; *Metals, Heavy/toxicity/adverse effects ; Aged ; Risk Factors ; Adult ; Cadmium/toxicity/adverse effects ; *Environmental Exposure/adverse effects ; Mercury/toxicity/adverse effects ; Lead/toxicity/adverse effects ; Nutrition Surveys ; },
abstract = {Toxicological and histological evidence suggests that heavy metals accumulate in the retina, implicating their potential role in the development of age-related macular degeneration (AMD). However, most prior epidemiologic studies have focused on individual metal exposures, overlooking possible joint effects. This study assessed the association between co-exposure to lead (Pb), mercury (Hg), and cadmium (Cd) and AMD risk among Korean adults using 2008-2012 Korea National Health and Nutrition Examination Survey data. A total of 4818 participants aged 40 years or older were included. Logistic regression models evaluated single-metal associations, while quantile g-computation and Bayesian kernel machine regression (BKMR) assessed mixture effects. Participants in the third quartile of Pb had significantly higher odds of AMD (adjusted OR: 1.76, 95% CI: 1.07-2.88) than those in the lowest quartile. Quantile g-computation showed that a one-quartile increase in the metal mixture was associated with elevated AMD risk (adjusted OR: 1.20, 95% CI: 1.02-1.41). BKMR confirmed that the heavy metal mixture increased the risk of AMD, with Pb being the primary contributor in smokers and Cd in non-smokers. Our findings indicate that co-exposure to heavy metals elevates AMD risk and that the predominant contributing metal may differ depending on smoking status.},
}
@article {pmid40707177,
year = {2025},
author = {Agostini, HT and Silva, R and Holz, FG and Larsen, M and Altay, L and Souied, EH and Quiering, C and Rose, U and Liakopoulos, S and , },
title = {Impact of retinal thickness fluctuations with ranibizumab versus aflibercept in neovascular age-related macular degeneration (SALT): 12-month results from a multicentre, randomised, phase IV trial.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2024-326526},
pmid = {40707177},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: To compare fluctuations of central subfield retinal thickness (CSRT) in patients with neovascular age-related macular degeneration undergoing ranibizumab pro re nata versus aflibercept bimonthly treatment in a prospective 12 month, phase IV, randomised, multicentre study.<br><br>METHODS: Ranibizumab was administered according to best-corrected visual acuity (BCVA) and/or disease activity detected on spectral domain optical coherence tomography. Aflibercept was administered at three initial monthly visits followed by bimonthly treatment. CSRT stability was evaluated between months 3 and 6. CSRT stability was compared between groups and correlated with functional outcomes at month 12.<br><br>RESULTS: Fluctuations of CSRT showed a least-squares (LS) mean (95% CI) difference of -4.12 (-10.22 to 1.98) &#xb5;m between ranibizumab (25.16 (20.09 to 30.24) &#xb5;m) and aflibercept groups (29.28 (24.14 to 34.43) &#xb5;m) (p=0.1850). A predefined analysis of retinal stability, adjusted for baseline CSRT, showed a LS mean (95%&#x2009;CI) difference of -6.53 (-12.47 to -0.58&#x2009;&#xb5;m) in favour of ranibizumab (23.53 (18.58 to 28.49) &#xb5;m) versus aflibercept (30.06 (25.04 to 35.07) &#xb5;m) (p=0.0315). Pearson's correlation coefficient demonstrated no correlation between the mean amplitude of CSRT fluctuation between months 3 and 6, and BCVA at month 12 (r = -0.0888). Adverse event rates were low.<br><br>CONCLUSIONS: Numerical differences in retinal thickness fluctuations between months 3 and 6 were detected between treatment regimens. While the presence of fluctuations has previously been shown to have a negative impact on functional outcomes, our data showed no correlation between the mean amplitude of fluctuations and functional outcomes at month 12.},
}
@article {pmid40705272,
year = {2025},
author = {Syed, YY},
title = {SDZ-AFL: An Aflibercept Biosimilar.},
journal = {Clinical drug investigation},
volume = {45},
number = {9},
pages = {677-680},
pmid = {40705272},
issn = {1179-1918},
mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/adverse effects/pharmacokinetics/pharmacology/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Biosimilar Pharmaceuticals/therapeutic use/adverse effects/pharmacology/pharmacokinetics ; *Angiogenesis Inhibitors/therapeutic use/adverse effects/pharmacology/pharmacokinetics/administration &amp; dosage ; *Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; },
abstract = {SDZ-AFL (SOK583A1; Afqlir[®]) is a biosimilar of the reference intravitreal aflibercept, a vascular endothelial growth factor inhibitor. SDZ-AFL has been approved in the EU for the treatment of the same indications in adults as reference aflibercept: neovascular age-related macular degeneration (nAMD), visual impairment due to macular oedema secondary to retinal vein occlusion, visual impairment due to diabetic macular oedema and visual impairment due to myopic choroidal neovascularisation. SDZ-AFL has similar physicochemical and pharmacodynamic properties to those of reference aflibercept, and pharmacokinetic similarity has been demonstrated in patients with nAMD. SDZ-AFL demonstrated clinical efficacy equivalent to that of reference aflibercept in patients with nAMD and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of SDZ-AFL were similar to those of reference aflibercept. The role of reference aflibercept in the management of neovascular retinal diseases is well established, and SDZ-AFL provides an effective biosimilar alternative for patients requiring ophthalmic aflibercept therapy.},
}
@article {pmid40703032,
year = {2025},
author = {Ho, TC and Tsai, SH and Yeh, SI and Sun, MH and Tsao, YP},
title = {A PEDF-Derived Short Peptide Prevents Sodium Iodate-Induced Retinal Degeneration in Rats by Activating the SLC7A11/GSH/GPX4 Pathway in the RPE Cells.},
journal = {Journal of cellular and molecular medicine},
volume = {29},
number = {14},
pages = {e70693},
pmid = {40703032},
issn = {1582-4934},
support = {MOST 111-2314-B-195-011-MY3//Ministry of Science and Technology/ ; MMH-E-108-006//Mackay Memorial Hospital/ ; },
mesh = {Animals ; *Iodates/toxicity ; *Nerve Growth Factors/chemistry/pharmacology ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; *Eye Proteins/chemistry/pharmacology ; *Glutathione/metabolism ; Rats ; *Serpins/chemistry/pharmacology ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Amino Acid Transport System y+/metabolism ; *Retinal Degeneration/chemically induced/metabolism/pathology/prevention &amp; control/drug therapy ; *Signal Transduction/drug effects ; Humans ; Lipid Peroxidation/drug effects ; Oxidative Stress/drug effects ; Male ; Disease Models, Animal ; Cell Line ; Ferroptosis/drug effects ; Antioxidants/pharmacology ; Rats, Sprague-Dawley ; *Peptides/pharmacology ; },
abstract = {Retinal pigment epithelial (RPE) cell damage caused by oxidative stress is a key factor in the pathogenesis of dry age-related macular degeneration (AMD). 6dS peptide is derived from the neuroprotective motif of pigment epithelium-derived factor (PEDF) and has antioxidant effects. This study used the sodium iodate (SI, a chemical oxidant)-induced animal dry AMD model to investigate the 6dS-mediated antioxidant mechanism. 6dS reduced SI-induced cytotoxicity, including ferrous iron accumulation, lipid peroxidation, glutathione (GSH) depletion, and ferroptosis in ARPE-19 cells. SI injection in rats induced cell death and lipid peroxidation in the RPE layer, along with retinal atrophy and electrophysiological dysfunction, recapitulating features of dry AMD that were counteracted by 6dS eye drop treatment. Mechanistically, 6dS induced the expression of SLC7A11 (solute carrier family seven member 11) and glutathione peroxidase 4 (GPX4) to alleviate SI-induced GSH depletion and lipid peroxidation. Inhibitors targeting the PEDF receptor, SLC7A11, and GPX4 abolished the 6dS effect. Our study proposes an antioxidant mechanism through which PEDF receptor signalling links to the SLC7A11/GSH/GPX4 axis to alleviate intracellular redox imbalance. These findings suggest that 6dS eye drops may be a promising treatment for dry AMD.},
}
@article {pmid40701607,
year = {2025},
author = {Zhang, Z and Zhang, X and Zhang, R and Gao, Y},
title = {Trends and drivers of blindness and vision loss burden attributable to age-related macular degeneration from 1990 to 2021: findings from the Global Burden of Disease Study 2021.},
journal = {BMJ open},
volume = {15},
number = {7},
pages = {e094953},
pmid = {40701607},
issn = {2044-6055},
mesh = {Humans ; *Macular Degeneration/complications/epidemiology ; *Blindness/epidemiology/etiology ; Global Burden of Disease/trends ; Cross-Sectional Studies ; Prevalence ; Aged ; Male ; Female ; Disability-Adjusted Life Years ; Aged, 80 and over ; Global Health ; Middle Aged ; Cost of Illness ; },
abstract = {OBJECTIVES: To investigate the trends and drivers of the burden of blindness and vision loss (BVL) attributable to age-related macular degeneration (AMD) from 1990 to 2021.<br><br>DESIGN: Cross-sectional study.<br><br>SETTING: Studies from the Global Burden of Disease (GBD) Study 2021 database, generated from population-representative data sources identified through a literature review and research collaborations, were included.ParticipantsBVL attributable to AMD participants.<br><br>OUTCOMES: Total numbers and age-standardised rates of prevalence and disability-adjusted life years (DALYs) were the main outcomes. Secondary outcomes consisted of the temporal trends in the BVL burden attributable to AMD at global, regional and national levels, using an age-period-cohort model, and factors influencing changes in BVL burden attributable to AMD, using decomposition analysis.<br><br>RESULTS: Age-standardised prevalence and DALY rates of BVL attributable to AMD showed a decreasing trend, with a global net drift in prevalence of -0.35% (95% CI: -0.38 to -0.32) per year. Globally, we observed unfavourable age effects, subtle period effects and positive cohort effects on prevalence. Over the past three decades, the global increase in prevalence and DALYs of BVL attributable to AMD was primarily due to population growth and ageing.<br><br>CONCLUSIONS: Our research indicates that the population growth and ageing have exacerbated the burden of BVL attributable to AMD over the past 30 years. We identified countries with substantial room for improvement and those with exemplary performance to inspire potential ideas for better managing BVL attributable to AMD.},
}
@article {pmid40701533,
year = {2025},
author = {Zhang, W and Huang, S},
title = {Circadian rhythms in ophthalmic diseases.},
journal = {Experimental eye research},
volume = {259},
number = {},
pages = {110533},
doi = {10.1016/j.exer.2025.110533},
pmid = {40701533},
issn = {1096-0007},
mesh = {Humans ; *Circadian Rhythm/physiology ; *Eye Diseases/physiopathology ; Animals ; },
abstract = {Circadian rhythms, governed by the suprachiasmatic nucleus of the hypothalamus, orchestrate a wide range of physiological processes, including those implicated in ophthalmic diseases. These biological rhythms influence both normal ocular function and disease pathogenesis, with many ophthalmic conditions exhibiting altered circadian rhythmicity in frequency or amplitude. Disruptions to circadian homeostasis may exacerbate disease symptoms and negatively affect treatment outcomes, ultimately impairing patients' quality of life. Emerging evidence supports a strong interplay between circadian rhythm dysregulation and the development of ocular disorders. A comprehensive understanding of these temporal disruptions could deepen insights into disease mechanisms and facilitate the development of circadian-based therapeutic strategies. This review examines circadian alterations in ophthalmic diseases-such as dry eye disease, glaucoma, diabetic retinopathy, age-related macular degeneration, and cataracts-and discusses potential circadian-regulated interventions and directions for future research.},
}
@article {pmid40701514,
year = {2025},
author = {Amatha, S and Das, R and Gautam, MK and Mondal, S},
title = {Biotechnological novel drug delivery systems for age-related macular degeneration.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {100},
number = {9},
pages = {537-548},
doi = {10.1016/j.oftale.2025.07.010},
pmid = {40701514},
issn = {2173-5794},
mesh = {Humans ; *Macular Degeneration/drug therapy/therapy ; *Drug Delivery Systems/methods ; Genetic Therapy/methods ; *Biotechnology ; Precision Medicine ; Cell- and Tissue-Based Therapy/methods ; },
abstract = {Recent years have witnessed remarkable advancements in biotechnological ocular drug delivery systems, introducing novel strategies such as gene therapy, cell-based systems, and targeted carriers. This article focuses specifically on age-related macular degeneration (AMD), the most prevalent ocular condition. While gene therapy holds promise for AMD treatment, it also presents significant challenges, leading to the exploration of cell-based therapy as a complementary or alternative approach. To address these hurdles and ensure successful market translation, new companies often form collaborative expert teams encompassing all relevant fields, including regulatory affairs. As medical science continues to evolve, a comprehensive understanding of gene therapy, cell-based delivery, biocompatibility, safety considerations, regulatory aspects, and ongoing clinical trials is essential to fully grasp the safety and effectiveness of these novel ocular therapies. Consequently, this paper primarily explores these key areas. The successful evolution of biotechnological ocular delivery signals a positive shift towards personalized medicine, which is expected to significantly improve the quality of life for AMD patients in the near future.},
}
@article {pmid40701376,
year = {2025},
author = {Wu, E and Hasan, N and Vupparaboina, S and Jiang, J and Du, K and DeCicco, J and Sadeghi, E and Zhang, M and Vupparaboina, KK and Bollepalli, SC and Eller, AW and Sahel, JA and Chhablani, J},
title = {Predicting Early Onset of Age-Related Macular Degeneration: A Machine Learning Approach.},
journal = {American journal of ophthalmology},
volume = {279},
number = {},
pages = {156-164},
doi = {10.1016/j.ajo.2025.07.020},
pmid = {40701376},
issn = {1879-1891},
mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Macular Degeneration/diagnosis/epidemiology ; *Machine Learning ; Aged ; Middle Aged ; Case-Control Studies ; ROC Curve ; Age of Onset ; Risk Factors ; United States/epidemiology ; Comorbidity ; Aged, 80 and over ; },
abstract = {PURPOSE: Develop a machine learning model that predicts early-onset AMD based on early patient comorbidities DESIGN: Retrospective case-control study.<br><br>SUBJECTS: This study used 2 datasets: a tertiary eye care center dataset (930 AMD patients, 392 early-onset, 538 late-onset) and the All of Us dataset for validation (560-580 AMD patients early-onset, 560-580 matched controls without AMD).<br><br>METHODS: Health records of AMD patients from a tertiary hospital (1999-2023) and the All of Us Research Program, a nationwide longitudinal cohort of U.S. adults (data collected 6/2016-2/2025) were collected. Unsupervised clustering using Uniform Manifold Approximation and Projection (UMAP) was performed on the tertiary eye care center dataset to identify distinct patient subgroups. Supervised machine learning models, including gradient-boosted decision trees (GBDT), logistic regression, and random forests, were trained to predict early-onset AMD.<br><br>MAIN OUTCOMES MEASURES: Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), while feature importance was assessed using the Gini index for tree-based models and coefficient magnitudes for logistic regression. Additionally, odds ratios for comorbidities associated with early-onset AMD were estimated using 2 &#xd7; 2 contingency tables in the validation dataset (All of Us).<br><br>RESULTS: Clustering identified 2 distinct patient groups, with 1 (93.08% early-onset AMD dominated) showing high rates of inflammatory joint disorders, hypertension, and dyslipidemia. Multiple supervised machine learning models achieved &#x223c;76% accuracy in predicting early-onset AMD from early comorbidities (diagnosed before age of 55). Like clustering, analysis of supervised machine learning models identified inflammatory joint disorders, hypertension, and dyslipidemia as the most predictive features. These comorbidities were validated using the All of Us dataset, with essential hypertension (OR: 5.80, 95% CI: [4.25-7.93], P < .05), rheumatoid arthritis (OR: 4.61, 95% CI: [1.55-13.72], P < .05), and hyperlipidemia (OR: 5.16, 95% CI: [3.76-7.08], P < .05) showing strong associations with early-onset AMD.<br><br>CONCLUSION: Screening hypertension, dyslipidemia, and inflammatory joint disorders in ophthalmologic evaluations may enable earlier AMD detection and intervention.},
}
@article {pmid40700755,
year = {2025},
author = {Faes, L and Holekamp, N and Benyamini, G and Nahen, K and Mohan, N and Freund, KB},
title = {Home Optical Coherence Tomography-guided Management of Type 3 Macular Neovascularization.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001792},
pmid = {40700755},
issn = {1937-1578},
abstract = {PURPOSE: To explore the impact of home optical coherence tomography (OCT)-guided treatment personalization for type 3 macular neovascularization (MNV) in age-related macular degeneration (AMD).<br><br>METHODS: A prospective home OCT trial of a patient with a one-month history of type 3 MNV under anti-angiogenic treatment (two "loading" injections). During the 23.4-week study period, the patient's treatment regimen was managed through regular self-imaging, enabling continuous monitoring of retinal fluid dynamics.<br><br>RESULTS: Over the observation period, the patient performed 143 home OCT measurements (mean 6.1 per week, standard deviation 1), which prompted three in-office visits where three anti-angiogenic injections were delivered at the discretion of the investigator. The mean individualized treatment intervals established through home OCT were 8 weeks, with the patient maintaining stable visual acuity at 20/20 Snellen. Complete resolution of intraretinal fluid was noted between injection. Notably, home OCT revealed unexpected fluctuations in retinal fluid measured as hyporeflective spaces in the absence of treatment. Two out of three injections were administered after the retinal fluid volume had decreased by more than half within two, and eight days following an initial transient spike.<br><br>CONCLUSION: The neovascular subtype as defined by the Consensus Nomenclature for Reporting Neovascular AMD Data (CONAN) may serve as a useful management framework when approaching home OCT guided treatment decisions. In type 3 disease, home OCT-guided management demonstrates significant potential for optimizing treatment. Further research is warranted to elucidate the dynamics of retinal fluid variations in different MNV subtypes.},
}
@article {pmid40700658,
year = {2025},
author = {Tran, M and Agnihotri, AP and Nagel, ID and Wagner, N and Nudleman, E and Borooah, S},
title = {Rapid progression of maculopathy after Pentosan Polysulfate Sodium cessation.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001791},
pmid = {40700658},
issn = {1937-1578},
abstract = {PURPOSE: To report a case of pentosan polysulfate sodium (PPS) maculopathy showing rapid progression of retinopathy 4 years after discontinuing PPS.<br><br>METHODS: A 75-year-old woman presenting with gradual vision changes underwent comprehensive examination including multimodal imaging and genetic testing.<br><br>RESULTS: A 75-year-old woman presented with a history of intermediate age-related macular degeneration and progressive blurring of her central vision beginning at 69 years of age. Fundoscopic examination revealed retinal pigment epithelium (RPE) abnormalities and multifocal outer retinal loss. The patient had been first prescribed PPS for interstitial cystitis (IC) aged 63 with a cumulative PPS dose of approximately 1300 grams and ceased PPS at 71 years of age. She was noted to have only minimal retinal changes prior to drug cessation. Four years post-cessation, the patient reported marked night vision and color vision abnormalities and was noted to have severe retinal changes including macular atrophy. Genetic testing revealed the patient to be homozygous for the previously reported risk alleles.<br><br>CONCLUSION: PPS maculopathy is an acquired toxic disease that can significantly impact a patient's quality of life. Our report highlights that marked progression of PPS retinopathy can occur even after drug cessation and that patients need to be carefully monitored and given supportive management.},
}
@article {pmid40700079,
year = {2025},
author = {Trinquet, L and Ajasse, S and Chavane, F and Legras, R and Matonti, F and Sahel, JA and Vignal-Clermont, C and Lorenceau, J},
title = {Uncovering the Characteristics of Pupil Cycle Time (PCT) in Neuropathies and Retinopathies.},
journal = {Vision (Basel, Switzerland)},
volume = {9},
number = {3},
pages = {},
pmid = {40700079},
issn = {2411-5150},
abstract = {Pupil cycle time (PCT) estimates the dynamics of a biofeedback loop established between pupil size and stimulus luminance, size or colour. The PCT is useful for probing the functional integrity of the retinopupillary circuits, and is therefore potentially applicable for assessing the effects of damage due to retinopathies or neuropathies. In previous studies, PCT was measured by manually counting the number of pupil oscillations during a fixed period to calculate the PCT. This method is scarce, requires a good expertise and cannot be used to estimate several PCT parameters, such as the oscillation amplitude or variability. We have developed a computerised setup based on eye-tracking that expands the possibilities of characterising PCT along several dimensions: oscillation frequency and regularity, amplitude and variability, which can be used with a large palette of stimuli (different colours, sizes, shapes or locations), and further allows measuring blinking frequency and eye movements. We used this method to characterise the PCT in young control participants as well as in patients with several pathologies, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), Stargardt disease (SD), and Leber hereditary optic neuropathy (LHON). We found that PCT is very regular and stable in young healthy participants, with little inter-individual variability. In contrast, several PCT features are altered in older healthy participants as well as in ocular diseases, including slower dynamics, irregular oscillations, and reduced oscillation amplitude. The distinction between patients and healthy participants based on the calculation of the area under the curve of the receiver operating characteristics (AUC of ROC) were dependent on the pathologies and stimuli (0.7 < AUC < 1). PCT nevertheless provides relevant complementary information to assess the physiopathology of ocular diseases and to probe the functioning of retino-pupillary circuits.},
}
@article {pmid40699817,
year = {2025},
author = {Harej Hrkać, A and Pelčić, A and Čaljkušić-Mance, T and Mršić-Pelčić, J and Pilipović, K},
title = {The Preventive Power of the Mediterranean Diet Against Blue-Light-Induced Retinal Degeneration: Is the Secret in the Herbs and Spices?.},
journal = {Current issues in molecular biology},
volume = {47},
number = {6},
pages = {},
pmid = {40699817},
issn = {1467-3045},
support = {uniri-iskusni-biomed-23-82//University of Rijeka/ ; },
abstract = {The Mediterranean diet, rich in plant-based foods, healthy fats, and herbs, has long been associated with a range of health benefits, including cardiovascular, neuroprotective, and anti-inflammatory effects. Recent studies suggest that certain components of this diet, particularly spices such as bay laurel, thyme, oregano, sage, and rosemary, may play a critical role in protecting the retina from oxidative damage, a key factor in blue-light-induced retinal degeneration. Blue light, emitted by digital screens and artificial lighting, has been implicated in the development of retinal conditions like age-related macular degeneration by inducing oxidative stress and inflammation. This review explores the potential of the herbs and spices commonly present in the Mediterranean diet to mitigate blue-light-induced retinal damage. These herbs are rich in polyphenols, flavonoids, essential oils, and terpenes, which offer antioxidant, anti-inflammatory, and antimicrobial properties, contributing to retinal health and reducing oxidative damage. By focusing on bioactive compounds such as eucalyptol (1,8-cineole), rosmarinic acid, carnosic acid, eugenol, and thymol, this article investigates how these herbs and spices might act as natural protectants against blue-light-induced stress and retinal degeneration. The findings highlight the promising role of these culinary staples in preventing retinal damage and offer insights into future dietary recommendations for eye health in an increasingly digital world.},
}
@article {pmid40699623,
year = {2025},
author = {Zubieta, D and Warden, C and Bhattacharya, S and Brantley, MA},
title = {Tauroursodeoxycholic Acid Confers Protection Against Oxidative Stress via Autophagy Induction in Retinal Pigment Epithelial Cells.},
journal = {Current issues in molecular biology},
volume = {47},
number = {4},
pages = {},
pmid = {40699623},
issn = {1467-3045},
support = {GF02528//International Retinal Research Foundation/ ; },
abstract = {Tauroursodeoxycholic acid (TUDCA) has been shown to protect against oxidative damage in retinal pigment epithelial (RPE) cells. However, the mechanisms by which it mediates these protective effects have not been thoroughly investigated in the context of age-related macular degeneration (AMD) disease onset and progression. We measured LC3-II and p62 expression via Western blot and immunohistochemistry in RPE cells treated with H2O2, TUDCA, or a combination of both to measure autophagy induction. To determine autophagy flux, we measured the expression of LC3-II/LC3-I in RPE cells in the presence of bafilomycin via Western blot. To determine the mechanistic pathways of TUDCA-induced autophagy, we measured the protein expression of autophagy regulators (Atg5, Beclin-1, S6, AMPK, and Akt) via Western blot. We show that TUDCA-mediated autophagy induction confers protection of RPE cells against oxidative damage via mTORC1/mTORC2 independent pathways but depends on Atg5. Our work adds to the overall understanding of RPE cell homeostasis and highlights the role of TUDCA in maintaining RPE health.},
}
@article {pmid40698627,
year = {2025},
author = {Beit-Yannai, E},
title = {Exosomes in Ocular Health and Disease.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/02713683.2025.2515996},
pmid = {40698627},
issn = {1460-2202},
abstract = {PURPOSE: Exosomes, small extracellular vesicles ranging from 30 to 150 nm in diameter, have emerged as crucial mediators of intercellular communication in ocular tissues. This review explores the roles of exosomes in ocular health and disease, focusing on their biogenesis, functions in different eye structures, and potential as diagnostic biomarkers and therapeutic agents.<br><br>METHODS: This comprehensive review synthesizes current research on ocular exosomes, drawing from global studies to present an integrated view of exosome biology in the eye.<br><br>RESULTS: Exosomes play vital roles in maintaining retinal homeostasis, corneal function, and lens transparency. They are implicated in the pathogenesis of major eye diseases, including glaucoma, age-related macular degeneration, and diabetic retinopathy. Recent advances have revealed the potential of exosomes as biomarkers for early disease detection and as vehicles for targeted drug delivery. Emerging technologies, such as microfluidics and nanotechnology, enhance exosome isolation and analysis capabilities.<br><br>CONCLUSIONS: Exosome research in ophthalmology is rapidly advancing, offering promising avenues for novel diagnostic and therapeutic approaches. However, challenges remain in standardization, scalability, and clinical translation. Addressing these issues and ethical considerations will be crucial for realizing the full potential of exosomes in improving ocular health outcomes globally.},
}
@article {pmid40698349,
year = {2025},
author = {Okawa, K and Maruyama-Inoue, M and Chin, JY and Inoue, T and Yanagi, Y and Kadonosono, K},
title = {One-Year Outcomes of Intravitreal Faricimab Injection in Treatment-Naïve Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251352888},
pmid = {40698349},
issn = {2474-1272},
abstract = {Purpose: To investigate the 1-year functional and morphologic outcomes of intravitreal (IVT) faricimab in treatment-naïve Japanese patients with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study was performed to examine the outcomes of patients with nAMD who received IVT faricimab using a treat-and-extend regimen. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), central choroidal thickness, dry macular achievement, and treatment intervals at 48 weeks were evaluated. Furthermore, the presence of polypoidal lesions at 48 weeks, as indicated by indocyanine green angiography, was investigated in patients with polypoidal choroidal vasculopathy (PCV). Results: This study included 48 Japanese treatment-naïve patients with nAMD assessed at 1 year of follow-up. The BCVA was significantly improved 1 year after initial treatment (P < .001). CFT and central choroidal thickness were also significantly decreased after 1 year (P < .001 and P < .001, respectively). Dry macula was achieved in 42 eyes (87.5%), and the mean (±SD) treatment interval at 12 months was 14.5 ± 4.4 weeks. The 1-year polyp regression rate was 76.9% (10/13 eyes). Conclusions: IVT faricimab was well tolerated and appeared to improve both functional and anatomic outcomes in Japanese patients with nAMD. In addition, a high rate of polyp regression was seen in patients with PCV.},
}
@article {pmid40698098,
year = {2025},
author = {Ulusoy, MO and Erseven, C and Erel, B and Çevik, SG and Perente, &#x130;},
title = {The effect of the pandemic on the intravitreal injection treatment for patients with age-related macular degeneration, regardless of lockdown periods.},
journal = {Romanian journal of ophthalmology},
volume = {69},
number = {2},
pages = {164-168},
pmid = {40698098},
issn = {2501-2533},
mesh = {Humans ; Intravitreal Injections ; Male ; *COVID-19/epidemiology ; Female ; *Visual Acuity ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; Retrospective Studies ; *SARS-CoV-2 ; *Quarantine ; *Pandemics ; Tomography, Optical Coherence ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; *Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: To evaluate the impact of the pandemic on the intravitreal injection treatment routine for patients with neovascular age-related macular degeneration, regardless of lockdown periods.<br><br>METHODS: We evaluated the data of intravitreal injections between March 2020 and June 1, 2021, which was the last day of official restrictions. We divided into two groups: a regular treatment group and a group that was interrupted for at least 3 months without excuse. The initial visual acuity at the beginning of the pandemic, the last visual acuity, the visual acuity after interruption, the central macular thickness, and the interruption time were recorded.<br><br>RESULTS: A total of 156 patients' data were evaluated. There are forty-eight patients in the regular treatment group, 77 in the interruption group, and 31 in the discontinued group. The visual loss was significantly higher in the interruption group (respectively, -0.11 &#xb1; 0.19 vs. 0.03 &#xb1; 0.16, p<0.001). Central macular thickness changes were higher in the interruption group (respectively, 31.8 &#xb1; 5.7&#xb5;m vs. 13.5 &#xb1; 4.6, p<0.001). The mean interruption time was 6.71 &#xb1; 2.45 months.<br><br>DISCUSSION: Half of the patients in our study interrupted their treatment during the pandemic, and this interruption had a negative impact on their visual acuity and central macular thickness. In addition to COVID-19's own high mortality and morbidity, it also had adverse effects on patients who required regular follow-up and treatment.<br><br>CONCLUSION: Since interruptions in treatment negatively impact the prognosis of AMD, effective protocols that do not require frequent visits are necessary.},
}
@article {pmid40697394,
year = {2025},
author = {Guymer, RH and Blair, JPM and De Zanet, S and Apostolopoulos, S and Ciller, C and Wu, Z and , },
title = {Effect of Subthreshold Nanosecond Laser on Loss of OCT Outer Retinal Bands in Age-Related Macular Degeneration: A LEAD Study Report.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100839},
pmid = {40697394},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the effect of subthreshold nanosecond laser (SNL) treatment on the rate of loss of the OCT outer retinal bands in intermediate age-related macular degeneration (AMD).<br><br>DESIGN: Post hoc analysis of the Laser Intervention in the Early Stages of AMD (LEAD) study.<br><br>PARTICIPANTS: A subset of 285 of 292 individuals in the LEAD study with bilateral large drusen without signs of multimodal imaging-defined late AMD at baseline, seen at 1 follow-up visit where neovascular AMD (nAMD) was absent.<br><br>METHODS: Participants were randomized to receive SNL or sham treatment in 1 study eye at 6-monthly intervals and were reviewed for up to 36 months. OCT scans from all visits without nAMD were automatically segmented to examine between-group differences in the rate of change in external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE) loss in the entire central 5-mm diameter region, or only nondrusen areas in this region.<br><br>MAIN OUTCOME MEASURES: Between-group differences in the rate of ELM, EZ, and RPE loss.<br><br>RESULTS: Overall, there was no significant between-group difference in the rate of change in the loss of all OCT outer retinal band parameters (P &#x2265; 0.206). However, there was evidence of significant treatment effect modification based on the coexistence of reticular pseudodrusen (RPD) in the study eye when evaluating the rate of RPE loss in the entire central 5-mm diameter region, and for the rate of ELM, EZ, and RPE loss when considering only nondrusen areas in this region (P &#x2264; 0.006). In eyes without coexistent RPD, there was a significant slowing of the loss of all OCT outer retinal band parameters with SNL treatment (P &#x2264; 0.038 for all), whereas there was no significant between-group difference in all parameters in eyes with coexistent RPD (P &#x2265; 0.153 for all).<br><br>CONCLUSIONS: Subthreshold nanosecond laser treatment slowed the progressive loss of the OCT outer retinal bands in intermediate AMD in eyes without coexistent RPD. This study also showed for the first time the responsiveness of these novel outcome measures to treatment.<br><br>FINANCIAL DISCLOSURE: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40697392,
year = {2025},
author = {Jaskoll, S and Shwartz, Y and Kramer, A and Elbaz-Hayoun, S and Rinsky, B and Grunin, M and Tiosano, L and Levy, J and Vofo, BN and Chowers, I},
title = {Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100853},
pmid = {40697392},
issn = {2666-9145},
abstract = {PURPOSE: The risk for developing age-related macular degeneration (AMD) is associated with multiple genetic variants. We aim to evaluate the association of AMD genetic risk variants with specific features of the disease detected by OCT.<br><br>DESIGN: A retrospective cross-sectional study.<br><br>PARTICIPANTS: Subjects diagnosed with AMD and healthy controls (>50 years of age) from a single tertiary referral center.<br><br>METHODS: Genotyping of 52 single nucleotide polymorphisms associated with AMD was analyzed in 578 patients. Weighted genetic risk scores (WGRSs) were calculated for variants in genes encoding proteins involved in the complement cascade, lipid metabolism, and other pathways, respectively. A global WGRS was calculated for all 52 variants. OCT images were annotated for the presence of typical drusen, subretinal drusenoid deposits, hyperreflective foci (HRF), complete retinal pigmented epithelium and outer retinal atrophy (cRORA), and macular neovascularization.<br><br>MAIN OUTCOME MEASURES: Association of WGRS and individual genetic risk variants with specific disease features detected by OCT.<br><br>RESULTS: A positive correlation between the presence of drusen and the lipid WGRS was detected (r = 0.09, P = 0.02). Logistic regression analysis indicated associations between cRORA and the complement score (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.05-1.50; P = 0.01), as well as the global score (OR = 1.29, 95% CI 1.13-1.46; P < 0.001). Regression also showed an association of HRF with the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 variant (OR = 1.53, 95% CI 1.03-2.27; P = 0.03), the other pathways score (OR = 1.94, 95% CI 1.20-3.12; P = 0.007), and the global score (OR = 1.16, 95% CI 1.00-1.35; P = 0.04).<br><br>CONCLUSIONS: Weighted genetic risk scores based on risk variants for AMD are associated with specific disease features. Tighter association of the global WGRS compared to pathway-specific scores suggests that several pathways are involved in the development of specific disease features such as cRORA, drusen, and HRF.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40696851,
year = {2025},
author = {Wu, S and Zhou, X and Wang, L and Yu, D and Wang, Z and Xu, X},
title = {A Proteomic Study of Different Types of Diabetic Macular Edema.},
journal = {Current eye research},
volume = {50},
number = {10},
pages = {1029-1038},
doi = {10.1080/02713683.2025.2516806},
pmid = {40696851},
issn = {1460-2202},
mesh = {*Macular Edema/metabolism/pathology/therapy ; *Diabetes Complications/metabolism/pathology/therapy ; Proteomics ; Tandem Mass Spectrometry ; Humans ; *Proteins/metabolism ; Biomarkers/metabolism ; Wnt Signaling Pathway ; Up-Regulation ; Down-Regulation ; Male ; Female ; Middle Aged ; Aged ; Apoptosis ; Lipid Metabolism ; Vascular Endothelial Growth Factors/therapeutic use ; },
abstract = {PURPOSE: This study investigates distinct protein markers associated with different morphologic features of diabetic macular edema, focusing on diffuse retinal thickening, cystoid macular edema, and cystoid macular degeneration.<br><br>METHODS: A total of 48 eyes of 33 patients with diabetic macular edema were included in the study and categorized into the aforementioned groups. Preoperative aqueous humor samples were collected from nine diabetic macular edema patients and subjected to tandem mass spectrometry labeling using tandem mass tags quantitative proteomics analysis to compare protein profiles in the aqueous humor among the different morphologic features of diabetic macular edema.<br><br>RESULTS: The analysis revealed that the efficacy of anti-vascular endothelial growth factor treatment was significantly better in the diffuse retinal thickening and cystoid macular edema groups compared to the cystoid macular degeneration group (P&#x2009;<&#x2009;0.05). Differential expression analysis identified 31 upregulated and 43 downregulated proteins in the diffuse retinal thickening group compared to the cystoid macular degeneration group, with upregulated proteins associated with vasoconstriction, apoptotic processes, complement system, and peptidase inhibitors, and downregulated proteins associated with protein kinase and positive regulation of cell cycle regulation. Similarly, the cystoid macular edema group showed 31 upregulated and 32 downregulated proteins compared to the cystoid macular degeneration group, with upregulated proteins associated with the Wnt signaling pathway and extracellular matrix (ECM)-receptor interaction, and downregulated proteins associated with high-density lipoprotein (HDL), cholesterol positive regulation. The screening criteria for differentially expressed proteins were fold change >1.2 or <0.83 and P&#x2009;<&#x2009;0.05.<br><br>CONCLUSION: Associations were found between cystoid macular degeneration formation and factors like the complement system, apoptotic pathway, and lipid metabolizing factors, providing insights for further understanding diabetic macular edema pathogenesis.},
}
@article {pmid40696069,
year = {2025},
author = {Park, J and Han, K and Kim, B and Lee, K and Jang, HR and Yoon, JM and Lim, DH and Shin, DW},
title = {Risk of age-related macular degeneration according to the chronic kidney disease and proteinuria in Korea: a 10-year nationwide cohort study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {26595},
pmid = {40696069},
issn = {2045-2322},
support = {HI20C1073//Ministry of Health and Welfare/ ; },
mesh = {Humans ; *Proteinuria/complications/epidemiology ; Male ; Female ; Republic of Korea/epidemiology ; *Renal Insufficiency, Chronic/complications/epidemiology ; Middle Aged ; Aged ; *Macular Degeneration/epidemiology/etiology ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Adult ; Proportional Hazards Models ; Cohort Studies ; },
abstract = {The association between chronic kidney disease (CKD) and the risk of age-related macular degeneration (AMD) is unclear. Our study aimed to evaluate this relationship considering the potential impact of proteinuria. This retrospective cohort study used a large representative population sample from the Korean National Health Insurance Service database (2009-2019) of individuals who participated in a national health screening program in 2009. CKD was determined by estimated glomerular filtration rate (eGFR). Proteinuria was assessed using dipstick urinalysis. AMD was identified according to International Classification Disease, Tenth Revision, codes in claims data. The Cox regression hazards model was used to estimate the association between CKD and risk of AMD. Among 4,005,946 participants, 400,189 (10.0%) had CKD. There was no significant association between CKD and AMD, but a positive relationship was identified between proteinuria and AMD. In stratification analysis with age and sex, the risk of AMD was more evident in younger (< 65 years) than older individuals (P-interaction < 0.001) and in men than women (P-interaction < 0.001). A positive association between proteinuria and AMD risk was observed and was prominent in younger males.},
}
@article {pmid40694826,
year = {2025},
author = {Fineberg, A and Tiosano, A and Golan, N and Yacobi, B and Loebl, N and Smila Perchik, I and Dotan, A and Ehrlich, R and Gal-Or, O},
title = {NEAR-INFRARED REFLECTANCE IMAGING FOR THE ASSESSMENT OF GEOGRAPHIC ATROPHY USING DEEP LEARNING.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {2311-2318},
doi = {10.1097/IAE.0000000000004614},
pmid = {40694826},
issn = {1539-2864},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Deep Learning ; Aged ; Male ; Female ; Middle Aged ; Aged, 80 and over ; *Tomography, Optical Coherence/methods ; Spectroscopy, Near-Infrared/methods ; Retrospective Studies ; Fluorescein Angiography/methods ; Fundus Oculi ; },
abstract = {PURPOSE: Near-infrared reflectance imaging is a widely available but underused modality for assessing geographic atrophy (GA), a late-stage manifestation of dry age-related macular degeneration. The aim of this study was to develop and evaluate a fully automated deep-learning-based approach for detecting GA on near-infrared reflectance imaging.<br><br>METHODS: Near-infrared reflectance images of patients aged 50 years or older with GA, confirmed by two retinal specialists, were analyzed at Rabin Medical Center. The control group included near-infrared reflectance images of patients with healthy-appearing retinas. Models were trained and evaluated based on accuracy, precision, sensitivity, F1 Score, and DICE coefficient.<br><br>RESULTS: A total of 113 GA patients and 119 controls were included. The classification data set contained 330 images, and the localization data set included 659 images. Classification models performed well, with accuracy above 95%, while Vision Transformer B16 achieved the best results (precision = 98.5%, sensitivity = 98.4% and accuracy = 98.5%). For GA localization, YOLOv8-Large achieved 91% sensitivity, 91% precision, IoU of 84%, and DICE coefficient of 88%.<br><br>CONCLUSION: Geographic atrophy can be reliably identified using near-infrared reflectance images. Deep learning models can assist in evaluating GA on this routinely available imaging modality, aiding in the selection of patients who may benefit from emerging therapies.},
}
@article {pmid40694413,
year = {2025},
author = {Power, D and Elstrott, J and Schallek, J},
title = {Photoreceptor loss does not recruit neutrophils despite strong microglial activation.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {40694413},
issn = {2050-084X},
support = {EY028293/EY/NEI NIH HHS/United States ; P30 EY001319/EY/NEI NIH HHS/United States ; Career Advancement Award//Research to Prevent Blindness/ ; Department of Ophthalmology Unrestricted Grant//Research to Prevent Blindness/ ; David Mahoney Neuroimaging Award//Dana Foundation/ ; Collaborative Research Grant//Genentech, Inc./ ; },
mesh = {Animals ; *Microglia/physiology/immunology ; *Neutrophils/immunology/physiology ; Mice ; Ophthalmoscopy/methods ; Tomography, Optical Coherence ; Mice, Inbred C57BL ; Retina/pathology ; *Photoreceptor Cells, Vertebrate/pathology ; },
abstract = {In response to central nervous system (CNS) injury, tissue-resident immune cells such as microglia and circulating systemic neutrophils are often first responders. The degree to which these cells interact in response to CNS damage is poorly understood, and even less so, in the neural retina, which poses a challenge for high-resolution imaging in vivo. In this study, we deploy fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) to study microglia and neutrophils in mice. We simultaneously track immune cell dynamics using label-free phase-contrast AOSLO at micron-level resolution. Retinal lesions were induced with 488 nm light focused onto photoreceptor (PR) outer segments. These lesions focally ablated PRs, with minimal collateral damage to cells above and below the plane of focus. We used in vivo AOSLO, and optical coherence tomography (OCT) imaging to reveal the natural history of the microglial and neutrophil response from minutes to months after injury. While microglia showed dynamic and progressive immune response with cells migrating into the injury locus within 1 day after injury, neutrophils were not recruited despite close proximity to vessels carrying neutrophils only microns away. Post-mortem confocal microscopy confirmed in vivo findings. This work illustrates that microglial activation does not recruit neutrophils in response to acute, focal loss of PRs, a condition encountered in many retinal diseases.},
}
@article {pmid40692491,
year = {2025},
author = {Ambresin, A and Quist, SW and Boer, M and Maamari, S and Barthelmes, D},
title = {Cost-minimisation analysis of anti-VEGF therapies in neovascular age-related macular degeneration and diabetic macular oedema in Switzerland.},
journal = {Journal of medical economics},
volume = {28},
number = {1},
pages = {1198-1213},
doi = {10.1080/13696998.2025.2536420},
pmid = {40692491},
issn = {1941-837X},
mesh = {Humans ; Recombinant Fusion Proteins/economics/therapeutic use/administration &amp; dosage ; Switzerland ; *Macular Edema/drug therapy/economics ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Ranibizumab/economics/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/economics/therapeutic use/administration &amp; dosage ; *Macular Degeneration/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Diabetic Retinopathy/drug therapy ; Biosimilar Pharmaceuticals/economics/therapeutic use/administration &amp; dosage ; Models, Econometric ; Aged ; Male ; Intravitreal Injections ; Female ; },
abstract = {OBJECTIVE: This study compares the direct healthcare costs of anti-VEGF therapies, including treat-and-extend (T&amp;E) and other durable regimens, for unilateral neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO) in Switzerland.<br><br>METHODS: An adapted cost-minimisation model estimated healthcare costs over two years for aflibercept 2&#x2009;mg, aflibercept 8&#x2009;mg, faricimab, ranibizumab, and ranibizumab biosimilars using clinical trial injection frequencies. Break-even analyses identified the medication prices and injection frequencies required for higher-cost therapies to achieve cost parity with the least expensive options. A one-way sensitivity analysis (OWSA) assessed key drivers of cost outcomes.<br><br>RESULTS: Aflibercept 8&#x2009;mg was estimated to be associated with the lowest treatment costs for both indications (CHF 11,814 for nAMD; CHF 11,242 for DMO). Faricimab (CHF 13,737) and aflibercept 2&#x2009;mg (CHF 15,243) followed in nAMD and DMO. Ranibizumab and its biosimilars incurred the highest costs: for nAMD, biosimilars ranged from CHF 16,243 to CHF 17,497 and the reference product reached CHF 18,424; for DMO, biosimilars ranged from CHF 18,187 to CHF 19,596, with the reference product at CHF 20,637. Break-even analyses for nAMD showed that prices would need to drop by -22% (faricimab, CHF 644) to -64% (ranibizumab reference, CHF 218) relative to aflibercept 8&#x2009;mg. For DMO, reductions ranged from -42% (aflibercept 2&#x2009;mg, CHF 493) to -81% (ranibizumab reference, CHF 114). The OWSA highlighted medication price and injection frequency as primary cost drivers.<br><br>CONCLUSIONS: This study estimated that the potentially minimized injection frequency of aflibercept 8&#x2009;mg in a clinical trial regimen may result in the lowest treatment costs for nAMD and DMO, followed by faricimab and aflibercept 2&#x2009;mg, respectively.},
}
@article {pmid40691808,
year = {2025},
author = {Hassan, TA and Abouelela, YS and Rizk, H and Tolba, A},
title = {Potential therapeutic applications of stem cells in animal models of ocular affections.},
journal = {Inflammation and regeneration},
volume = {45},
number = {1},
pages = {23},
pmid = {40691808},
issn = {1880-9693},
abstract = {BACKGROUND: Ocular affections are serious damage to the ocular tissue that results in impaired vision or blindness. Cell-based therapies are a potentially effective therapeutic technique that entails using stem-like precursor cells to induce differentiation of specific cell types and implanting the cells to improve vision in the affected tissue area.<br><br>METHODS: Numerous clinical trials were started to investigate the potential benefits of stem cells for treating ocular affections, based on several encouraging findings from the preclinical research. Following our review, data were collected from various databases, "Google Scholar, Springer, Elsevier, Egyptian Knowledge Bank, ProQuest, and PubMed" using different keywords such as corneal ulcer, retinopathy, glaucoma, ocular regeneration, and stem cells to investigate the various methods for regeneration of ocular affections. The data were obtained and analyzed.<br><br>RESULTS: This review includes tables that show all types of stem cells that were used to treat ocular diseases, such as mesenchymal stem cells (MSCs), hematopoietic stem cells, neural stem cells, embryonic stem cells, and induced pluripotent stem cells. The several characteristics of MSCs that aid in the restoration and regeneration of injured ocular tissue are outlined in this paper, along with their potential applications in the management of ocular degenerative diseases, as determined by physical, histological, immunohistochemical, and biochemical evaluations. Finally, our review highlights the most effective regenerative strategies that assist in rapid ocular regeneration in a variety of animal models, including mice, rats, rabbits, and goats.<br><br>CONCLUSION: With the promising results of multiple preclinical studies, stem cell therapy is still a great choice for treating ocular degenerative illnesses. To improve the clinical outcomes, co-transplantation of two or more cell types may be a possibility for future treatment alternatives.},
}
@article {pmid40691727,
year = {2025},
author = {Tang, F and Chandra, S and Grewal, MK and Raza, SA and Wijesingha, N and Faes, L and Fu, DJ and Tsai, WS and Lim, A and Sivaprasad, S},
title = {Determinants of visual functions in patients with early and intermediate age-related macular degeneration: the PEONY study.},
journal = {Eye (London, England)},
volume = {39},
number = {14},
pages = {2686-2693},
pmid = {40691727},
issn = {1476-5454},
support = {1906//Fight for Sight UK/ ; },
mesh = {Humans ; Male ; Female ; *Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; Aged ; Middle Aged ; *Macular Degeneration/physiopathology/diagnosis ; Retinal Drusen/physiopathology ; Geographic Atrophy/physiopathology ; Aged, 80 and over ; Color Vision/physiology ; },
abstract = {BACKGROUND/OBJECTIVES: Although decline in visual functions have been reported in eyes with non-advanced age-related macular degeneration (AMD), it is not known if visual functions in these eyes are influenced by structural changes on optical coherence tomography (OCT). We investigated the association between known OCT changes with photopic and scotopic visual functions.<br><br>SUBJECTS/METHODS: Participants aged 55 years or over with early or intermediate AMD in at least 1 eye, and controls with healthy maculae and were included. Associations between visual functions and retinal structural changes were investigated using linear regression and survival analysis.<br><br>RESULTS: We found that the presence of refractile drusen and nascent geographic atrophy (nGA) and were associated with poorer best-corrected visual acuity (BCVA), low luminance VA (LLVA), and increased low luminance deficit (LLD) (P&#x2009;<&#x2009;0.05). In survival analysis, eyes with thicker subfoveal choroidal thickness (SFCT) had a higher hazard rate of rod intercept, suggesting a decreased rod-intercept time (RIT). Eyes with nGA, drusen, refractile drusen, subretinal drusenoid deposits (SDD) have a significantly lower hazard rate of rod intercept (i.e. increased RIT, P&#x2009;<&#x2009;0.05). Among them, thinner SFCT, drusen, and SDD were identified as independent factors associated with an increased RIT in the final multivariable model (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS AND RELEVANCE: Given the associations between visual functions with outer retinal layers thickness and presence of established precursors of progression to advanced AMD, our findings serve as a strong foundation for future investigations into the relationships between retinal phenotypes and functional changes.},
}
@article {pmid40691725,
year = {2025},
author = {Beaver, D and Hudson, C},
title = {Are surfers and scuba divers an overlooked at-risk group for age-related macular degeneration?.},
journal = {Eye (London, England)},
volume = {39},
number = {13},
pages = {2495-2496},
pmid = {40691725},
issn = {1476-5454},
}
@article {pmid40691408,
year = {2025},
author = {Torres-Villaros, H and Giocanti-Aurégan, A and Doan, S and Agard, E and Billant, J and Arbousoff, N and Matagrin, B and Fenniri, I and Dot, C},
title = {Continuous versus Intermittent Use of Tear Substitutes in Patients Treated with Anti-VEGF for Neovascular Age-Related Macular Degeneration: The TREDIA Study.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {9},
pages = {2231-2241},
pmid = {40691408},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this prospective randomized bicenter study was to compare the effects of continuous versus intermittent use of tear substitutes on the ocular surface and dry eye symptoms in patients receiving repeated and frequent intravitreal injections (IVIs) for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients with nAMD treated with anti-vascular endothelial growth factor (anti-VEGF) for more than 1 year at 4-8-week intervals were included. The intermittent treatment group received standard 1.5% povidone artificial tears for three days after each IVI, while the continuous treatment group received an ophthalmic lubricant emulsion with 0.18% sodium hyaluronate four times a day throughout the study. The primary endpoint was the mean change in Ocular Surface Disease Index (OSDI) score between baseline and the day of the fourth IVI. Secondary endpoints included the Schirmer test score, tear break-up time (TBUT), and Oxford staining score.<br><br>RESULTS: Sixty-five patients with mean age of 83.1&#x2009;&#xb1;&#x2009;6.0&#xa0;years who had previously received a mean number of 28.5&#x2009;&#xb1;&#x2009;20.3 IVIs were included. The mean OSDI score change from baseline was -6.6&#x2009;&#xb1;&#x2009;13.5 points in the continuous treatment group versus&#x2009;+0.6&#x2009;&#xb1;&#x2009;13.7 points in the intermittent treatment group (p&#x2009;=&#x2009;0.04). No significant differences in Schirmer test score, TBUT, and Oxford score were found between the groups.<br><br>CONCLUSIONS: Continuous use of tear substitutes in patients with nAMD receiving repeated and frequent IVIs could be beneficial in improving dry eye symptoms, as shown by a significant improvement in OSDI scores in our study, despite no substantial changes in other ocular surface metrics.<br><br>TRIAL REGISTRATION NUMBER: NCT06174181.},
}
@article {pmid40690698,
year = {2025},
author = {Tew, TB and Hsieh, YT and Tsui, MC and Hsia, Y and Lee, CY and Wang, SW and Huang, CJ and Ma, IH and Hung, KC and Lai, TT and Yang, CH and Yang, CM and Ho, TC},
title = {COMPARISON OF CHARACTERISTICS AND TREATMENT OUTCOMES OF TYPE 1 AND TYPE 2 MYOPIC CHOROIDAL NEOVASCULARIZATION AFTER ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {2279-2288},
pmid = {40690698},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Female ; Male ; *Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/drug therapy/diagnosis/etiology ; Intravitreal Injections ; *Myopia, Degenerative/complications/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Fluorescein Angiography/methods ; Aged ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Follow-Up Studies ; Fundus Oculi ; Adult ; },
abstract = {PURPOSE: This study aims to compare baseline characteristics and treatment outcomes of Type 1 and Type 2 myopic choroidal neovascularization (CNV) after 1 year of antivascular endothelial growth factors therapy and identify clinical factors associated with visual outcomes, recurrence rates, and injection numbers.<br><br>METHODS: In this retrospective study, we reviewed 171 patients with active myopic CNV treated with antivascular endothelial growth factors therapy and followed for at least 1 year. CNV types were classified using optical coherence tomography. Baseline characteristics, including best-corrected visual acuity, myopic maculopathy grade, and optical coherence tomography findings, were compared.<br><br>RESULTS: Type 1 CNVs (19.3% of cases) exhibited worse baseline best-corrected visual acuity and more advanced macular degeneration than Type 2 CNVs. Both types showed significant visual improvement equivalent to 2.2 lines post-therapy, with no difference in recurrence rates or injection numbers. Multivariate analysis revealed that baseline best-corrected visual acuity, severity of myopic macular degeneration, and presence of subretinal hyperreflective exudation were significant predictors of final best-corrected visual acuity, while CNV type was not an independent predictor.<br><br>CONCLUSION: Despite more severe macular degeneration in Type 1 CNV, both types myopic CNVs benefit significantly from antivascular endothelial growth factors therapy. These findings support extending treatment to Type 1 CNVs and highlight the need for individualized management strategies.},
}
@article {pmid40690116,
year = {2025},
author = {Kim, CY and Jeong, C and Han, Y and Hwang, C},
title = {Angiopoietin-1 and Tie2-Based Dual Cell Therapy Enhances Antiangiogenic Barrier Function in a Retina-Mimetic Model for Neovascular Retinal Disease.},
journal = {Tissue engineering and regenerative medicine},
volume = {22},
number = {6},
pages = {877-893},
pmid = {40690116},
issn = {2212-5469},
support = {RS-2023-00283544//Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare/ ; 2020IP0041//Asan Institute for Life Sciences, Asan Medical Center/ ; 2024IP0044//Asan Institute for Life Sciences, Asan Medical Center/ ; },
mesh = {Humans ; *Receptor, TIE-2/metabolism ; *Angiopoietin-1/metabolism/pharmacology ; Human Umbilical Vein Endothelial Cells/metabolism ; *Retina/pathology/metabolism ; *Cell- and Tissue-Based Therapy ; Cell Movement/drug effects ; Mesenchymal Stem Cells/metabolism/cytology ; Coculture Techniques ; Animals ; *Angiogenesis Inhibitors/pharmacology ; *Retinal Diseases/therapy/pathology/metabolism ; Retinal Pigment Epithelium ; Choroidal Neovascularization/therapy/pathology/metabolism ; },
abstract = {BACKGROUND: Choroidal neovascularization (CNV) is a major pathological process underlying retinal degenerative diseases such as wet age-related macular degeneration. While anti-VEGF therapies are widely used, limitations in response and vascular instability necessitate new approaches that promote both antiangiogenic effects and barrier restoration.<br><br>METHODS: A dual-cell therapy strategy was developed using human umbilical vein endothelial cells (HUVECs) genetically modified to overexpress Tie2 and mesenchymal stem cells (MSCs) engineered to secrete Angiopoietin-1 (Ang1). Antiangiogenic efficacy was evaluated using scratch assays, Transwell migration, and tube formation under VEGF stimulation. A retina-mimetic 2.5D co-culture system incorporating iPSC-derived RPE cells and mCherry-labeled ECs was used to assess endothelial invasion and epithelial barrier preservation.<br><br>RESULTS: Tie2/Ang1-modified cells significantly suppressed angiogenic behavior. Transwell migration showed OD595 crystal violet absorbance decreased from 3.54&#x2009;&#xb1;&#x2009;0.27 (control HUVEC) to 1.28&#x2009;&#xb1;&#x2009;0.08 (Tie2 overexpressed HUVEC in MSC Ang1 conditioned medium) under VEGF stimulation (p&#x2009;<&#x2009;0.01). Tube formation area cultured in VEGF dropped from 1.25&#x2009;&#xb1;&#x2009;0.05 in control group to 0.74&#x2009;&#xb1;&#x2009;0.07 in Tie2 overexpressed group cultured with MSC-Ang1 conditioned medium (p&#x2009;<&#x2009;0.01). In the retina-mimetic model, EC infiltration to the RPE monolayer across Transwell membrane decreased from 52.2&#x2009;&#xb1;&#x2009;8.5% in control HUVEC to 5.6&#x2009;&#xb1;&#x2009;4.3% with HUVEC-Tie2&#x2009;+&#x2009;Ang1 conditioned medium under VEGF (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: This study demonstrates that co-delivery of Ang1 and Tie2 via engineered ECs and MSCs synergistically inhibits VEGF-induced angiogenesis and choroidal migration while protecting epithelial barrier function. The retina-mimetic co-culture platform further validates the translational relevance of this dual-cell approach as a regenerative and antiangiogenic strategy in retinal vascular disease.},
}
@article {pmid40690044,
year = {2025},
author = {Limoli, C and O'Toole, L and Piccoli, G and Nucci, P and Vujosevic, S},
title = {Patients' awareness and presenting symptoms at the onset of neovascular age-related macular degeneration in two distinct European cohorts.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {304},
pmid = {40690044},
issn = {1573-2630},
mesh = {Humans ; Female ; Aged ; Male ; Aged, 80 and over ; Middle Aged ; Italy/epidemiology ; Surveys and Questionnaires ; Ireland/epidemiology ; *Wet Macular Degeneration/diagnosis/epidemiology/drug therapy/psychology ; *Awareness ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is a common ocular condition in the elderly population. If left untreated, it can lead to significant visual impairment. Prompt detection of the disease achieves better therapeutic outcomes. The goal of this study is to ascertain the presenting symptoms of nAMD from two different population groups.<br><br>METHODS: A questionnaire was distributed to two groups of patients with nAMD who attended intravitreal injection services in Milan and Dublin. Four age-subgroups were considered: 60-69, 70-79, 80-89,&#x2009;>&#x2009;90&#xa0;years. Patients completed an interview questionnaire regarding their symptoms at the time of diagnosis with nAMD. The patients were divided into two groups; Group A consisted of Italian patients and group B comprised Irish patients. Symptom differences between the groups were compared using the Chi-square test.<br><br>RESULTS: A total of 237 patients with nAMD were included in the study, with 136 in group A and 101 in group B. The most common age-subgroup was 80-89&#xa0;years (49.8%); the majority 129(54.4%) patients were females. The most frequently reported symptom at the time of nAMD onset was distortion (n&#x2009;=&#x2009;105, 44.3%). Notably, 50 patients (21.1%) were asymptomatic. The Irish patients were less aware of the onset of the symptoms of nAMD compared with their Italian counterparts(p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: This study shows that 21.1% of patients with nAMD were asymptomatic at the onset of their condition. Symptom awareness was higher among the Italian cohort compared to the Irish group. Patients at risk for conversion to nAMD should attend regular OCT monitoring rather than relying on subjective symptoms alone.},
}
@article {pmid40689796,
year = {2025},
author = {Hugi, F and Vollmer, J and Renaud, L and Machacek, M},
title = {A Semimechanistic Ocular Pharmacokinetic Model for ADVM-022 Gene Therapy Describing the Dose-Exposure Relationship in Monkeys and the Scaling to Human.},
journal = {Molecular pharmaceutics},
volume = {22},
number = {8},
pages = {4612-4623},
doi = {10.1021/acs.molpharmaceut.5c00155},
pmid = {40689796},
issn = {1543-8392},
mesh = {Animals ; Humans ; *Genetic Therapy/methods ; *Recombinant Fusion Proteins/pharmacokinetics/genetics/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/genetics/administration &amp; dosage ; *Genetic Vectors/administration &amp; dosage/genetics ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/genetics/antagonists &amp; inhibitors ; Dependovirus/genetics ; Macular Degeneration/therapy/genetics ; *Eye/metabolism ; },
abstract = {Gene therapies are emerging as a new treatment modality. Due to their novelty, general pharmacological properties have yet to be established. For example, the translation from animal models to humans for first-in-human dose selection and the dose-exposure relationship remain poorly characterized. A mechanistic and quantitative framework would improve preclinical program design, enable more robust first-in-human dose predictions, and support more rigorous dose adjustments during clinical development. This study establishes a semimechanistic mathematical model for aflibercept expression and pharmacokinetics (PK) following intravitreal (IVT) ADVM-022 administration in monkeys and humans, drawing on the preclinical and clinical data presently available. ADVM-022 is an AAV2.7m8-based viral vector that delivers the gene encoding aflibercept, an antivascular endothelial growth factor (VEGF) fusion protein. It was developed as a gene therapy for treating wet age-related macular degeneration (wAMD) and is administered through a single IVT injection. The proposed model incorporates established ocular PK for intravitreally administered proteins, along with an expression component that links AAV dose to aflibercept production. Based on pooled PK data from monkey studies, the model suggests that transduction occurs not only in the retina but also in other ocular tissues bordering the vitreous, contributing to the observed intraocular aflibercept levels. Increasing doses within the lower range of preclinical studies (3 × 10[10]-2 × 10[13] vg/eye) lead to increased transduction and expression, plateauing at upper limits of approximately 12.7 μg/day·cm[3] for the retina, and 0.785 μg/day for extra-retinal tissues at higher doses. Assuming similar transduction efficiency between humans and monkeys, with adjustments for anatomical differences, the model provided predictions of ocular aflibercept concentrations that aligned with observations from the two dose groups in the phase 1 OPTIC clinical trial, supporting the utility of this approach.},
}
@article {pmid40689724,
year = {2025},
author = {Neri, G and Rebecchi, C and Oakley, JD and Olivieri, C and Ricardi, F and Marolo, P and Russakoff, DB and Reibaldi, M and Borrelli, E},
title = {Deep Learning Model for Automated Classification of Macular Neovascularization Subtypes in AMD.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {9},
pages = {55},
pmid = {40689724},
issn = {1552-5783},
mesh = {Humans ; *Deep Learning ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Aged ; Male ; Female ; *Wet Macular Degeneration/classification/diagnosis ; ROC Curve ; Aged, 80 and over ; *Choroidal Neovascularization/classification/diagnosis ; Algorithms ; Middle Aged ; *Macula Lutea/pathology ; Sensitivity and Specificity ; },
abstract = {PURPOSE: To develop a deep learning algorithm capable of accurately classifying macular neovascularization (MNV) subtypes in patients with treatment-naïve exudative neovascular age-related macular degeneration (AMD) using structural optical coherence tomography (OCT) images.<br><br>METHODS: In this retrospective cohort study, a total of 193 eyes with treatment-na&#xef;ve neovascular AMD were included. Each case was classified into MNV subtypes (type 1, 2, or 3) based on structural OCT features. Convolutional neural network (CNN)-based deep learning models were trained using cross-validation to classify MNV subtypes. Preprocessing included homogenization of image data to optimize use of layer information for classification. Performance metrics included sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC), with and without homogenization.<br><br>RESULTS: Homogenized OCT data improved classification performance compared to non-homogenized data for all models. The highest reported sensitivity and specificity for type 1 MNV was 96.7% and 84.9%; for type 2, 100.0% and 85.5%; and, for type 3, 84.9% and 87.9%, respectively. The AUCs for type 1, 2, and 3 MNV were 0.95, 0.97, and 0.91, respectively. Occlusion sensitivity analysis revealed critical regions for classification, highlighting distinct anatomical differences among MNV subtypes.<br><br>CONCLUSIONS: The proposed deep learning model demonstrated high accuracy in classifying MNV subtypes on structural OCT, with improved performance following homogenization. This tool could assist clinicians in accurately and efficiently diagnosing MNV subtypes, potentially influencing treatment decisions and patient outcomes in neovascular AMD.},
}
@article {pmid40689376,
year = {2025},
author = {Kimura, K and Imai, K and Ueno, M and Sotozono, C},
title = {Assessment of the official national insurance coverage of regenerative medical products for ophthalmic diseases in Japan following regulatory approval.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {384-388},
pmid = {40689376},
issn = {2352-3204},
abstract = {INTRODUCTION: Recently, significant progress has been made in the field of regenerative medicine in Japan for the treatment of ophthalmic diseases, with a notable emphasis placed on clinical research and practical applications, and in 2014, one significant development was the initiation of the world's first clinical research using iPS cells for age-related macular degeneration. In addition, three regenerative medical products for the treatment of limbal stem cell deficiency, a rare and intractable ocular surface disease, have recently been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) under the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act (PMD Act). In order to expedite the practical implementation of regenerative medicine, the PMD Act presented a new category for regenerative medical products alongside the two categories that currently exist (i.e., 'pharmaceutical products' and 'medical devices'). However, within the current official Japanese national insurance coverage plan, there is no category designated for 'regenerative medical products'. Although the approval system for regenerative medical products differs from country to country (i.e., the United States Food and Drug Administration (U.S. FDA), the European Medicines Agency (EMA), etc.), in Japan, they are approved by the Japanese MHLW and PMDA. When manufacturers seek newly approved regenerative medical products in Japan to be incorporated within those listed in the Japanese national insurance coverage plan, the products are classified as either 'pharmaceutical products' or 'medical devices' and are reviewed by the Central Social Insurance Medical Council ("Chuikyo", in Japanese) of the Japanese MHLW. Although the responsibility for applying for regulatory approval and insurance coverage lies with the manufacturer, as the developer who conducted the clinical study and the investigator-initiated clinical trial for two ophthalmic regenerative medical products (i.e., Sakracy® and Vyznova®), we perceived that the period from regulatory approval to insurance coverage listing for these two products was longer than for other ophthalmic regenerative medical products. These experiences became the research question and the focus was on ophthalmic regenerative medical products, with the rationale behind this submission being that the dissemination of our experience will be of benefit to all clinical researchers and manufacturers. Hence, the purpose of this present study was to investigate the insurance coverage of regenerative medical products for ophthalmic diseases in Japan from the aspect of specific coverage-related categories.<br><br>METHODS: In this study, we investigated newly approved regenerative medical products for ophthalmic diseases in Japan after the Revised Pharmaceutical Affairs Act came into effect in 2014. The insurance coverage categories (i.e., 'pharmaceutical products' or 'medical devices') of each product and the period from regulatory approval to insurance coverage listing were examined based on publicly available materials from the Japanese MHLW.<br><br>RESULTS: As of the end of 2024, five products are included on the insurance coverage list. The period for Luxturna Injection&#xae; (Novartis Pharma), categorized as a pharmaceutical product, to be included was 65 days, which was within the standard administrative processing time for pharmaceutical products, (i.e., 60 days or less, yet no later than 90 days), while the elapsed periods for Nepic&#xae; and Ocural&#xae; (Japan Tissue Engineering), Sakracy&#xae; (CynosBio), and Vyznova&#xae; (Aurion Biotech Japan), which are categorized as medical devices, were 74, 173, 224, and 534 days, respectively. The periods for Sakracy&#xae; and Vyznova&#xae; exceeded the standard administrative processing time for medical devices, which in principle ranges from 5 to 6 months. Moreover, the elapsed period of time from regulatory approval to insurance coverage listing for Vyznova&#xae; was more than twice as long as that which occurred for Sakracy&#xae;.<br><br>CONCLUSIONS: Regenerative medical products categorized as medical devices are required to undergo a review process conducted by the Technical Committee for Insurance Materials on Medical Devices of the Japanese Central Social Insurance Medical Council. Our findings suggest that both manufacturers and regulatory authorities need to revise the Technical Committee's strategy from the aspect of putting regenerative medical products into practical clinical use in Japan.},
}
@article {pmid40689257,
year = {2025},
author = {Verghese, AP and Lasalle, CC and Ramsey, DJ},
title = {Dark Adaptometry Kinetics Differentiates Age-Related Macular Degeneration from Central Serous Chorioretinopathy.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100835},
pmid = {40689257},
issn = {2666-9145},
abstract = {PURPOSE: To assess the diagnostic utility of dark adaptometry (DA) rod intercept time (RIT) to differentiate age-related macular degeneration (AMD) from central serous chorioretinopathy (CSCR).<br><br>DESIGN: Retrospective consecutive case series.<br><br>PARTICIPANTS: Consecutive patients with a clinical diagnosis of AMD or CSCR who were &#x2265;50 years of age.<br><br>METHODS: The study included patients who had completed a DA study in &#x2265;1 eye measured at 5&#xb0; superior to the fovea on the retina. All patients underwent a comprehensive retina examination, including OCT assessment of the macula.<br><br>MAIN OUTCOME MEASURES: Patients were classified based on their RIT, with an RIT >6.50 minutes considered a delay.<br><br>RESULTS: The study included 67 patients with AMD and 25 with CSCR. Patients with AMD tended to be older (73.8 &#xb1; 8.9 years vs. 65.0 &#xb1; 7.2 years, P < 0.001) and were more likely female (53.7% vs. 28.0%, P = 0.049) compared with their CSCR counterparts. Additionally, patients with AMD tended to exhibit poorer vision in both their better-seeing (logarithm of the minimum angle of resolution 0.14 &#xb1; 0.13 vs. 0.08 &#xb1; 0.13, P = 0.057) and worse-seeing (logarithm of the minimum angle of resolution 0.48 &#xb1; 0.47 vs. 0.26 &#xb1; 0.25, P = 0.028) eyes. Rod intercept times were slower in patients with AMD compared with CSCR, both in the faster-adapting (12.44 &#xb1; 6.96 minutes vs. 4.01 &#xb1; 1.28 minutes, P < 0.001) and slower-adapting (13.06 &#xb1; 6.67 minutes vs. 4.95 &#xb1; 1.78 minutes, P < 0.001) eyes. Using a delayed RIT in the faster-adapting eye to classify patients with AMD versus CSCR showed excellent performance with a sensitivity of 79.1% (95% confidence interval [CI]: 67.4%-88.1%) and perfect specificity of 100.0% (95% CI: 86.3%-100.0%), yielding an accuracy of 97.4% (95% CI: 91.7%-99.6%). After adjusting for age, sex, and visual acuity, RIT in the faster-adapting eye remained an independent predictor of AMD versus CSCR.<br><br>CONCLUSIONS: Prolonged dark adaptation, indicated by a longer RIT, is capable of distinguishing individuals with AMD from CSCR, 2 conditions that share similar fundus features. Future investigations are warranted to assess the effectiveness of this noninvasive technique for AMD screening.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40689256,
year = {2025},
author = {Gabrielle, PH and Creuzot-Garcher, C},
title = {Re: Patel et al: Oral Antithrombotic Medication Is Associated with Improved Visual Acuity Outcomes in Eyes with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100840},
pmid = {40689256},
issn = {2666-9145},
}
@article {pmid40689254,
year = {2025},
author = {Schrittwieser, J and Birner, K and Coulibaly, LM and Schmidt-Erfurth, U and Reiter, GS},
title = {Exploiting Microperimetry as a Functional End Point in Healthy Aging and Different Stages of Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100850},
pmid = {40689254},
issn = {2666-9145},
abstract = {OBJECTIVE: To compare functional parameters between healthy aged eyes and different stages of age-related macular degeneration (AMD) based on functional parameters in microperimetry (MP) in 2 commonly used MP devices.<br><br>DESIGN: A prospective, cross-sectional study.<br><br>SUBJECTS: From 80 eyes from 80 subjects, 14 400 stimuli points were included.<br><br>METHODS: Subjects classified as healthy, intermediate AMD, neovascular AMD (nAMD), or geographic atrophy (GA) secondary to AMD were imaged with Spectralis HRA+OCT (Heidelberg Engineering) and underwent 2 consecutive examinations each, using the MP-3 (NIDEK) under photopic conditions and the MAIA (Centervue) under mesopic conditions. Pointwise sensitivity (PWS), mean sensitivity, range between highest and lowest PWS, fixation stability, and examination duration were compared between all 4 groups in both devices. Group comparison was performed using linear mixed-effects models and a discriminant analysis to find the parameters that best discriminated the respective AMD stage.<br><br>MAIN OUTCOME MEASURES: Pointwise sensitivity, range of the PWS, fixation metrics, and durations of the examinations.<br><br>RESULTS: The groups exhibited significant differences in PWS (P < 0.001) and mean sensitivity (P < 0.001), with healthy eyes showing the highest and late stages of AMD showing the lowest sensitivity values. In addition, GA showed significantly greater fixation stability compared with nAMD in the MP-3 at 2&#xb0; and 4&#xb0; (P = 0.014 and P = 0.008, respectively). The examination duration in healthy patients was significantly shorter compared with patients with GA (P = 0.041) in MP-3. No significant differences in fixation stability and duration between groups were observed with the MAIA device. The range between the highest and lowest PWS was the most effective parameter for discrimination, with a classification accuracy of 52.5% and 50.6% in the MP-3 and MAIA, respectively.<br><br>CONCLUSIONS: Retinal sensitivity declines with disease progression in AMD in both mesopic and photopic background illumination. The lowest retinal sensitivity was observed in patients with GA. Background illumination should be considered when selecting an MP device for a clinical trial.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40689128,
year = {2025},
author = {Motevasseli, T and Seraj, A and Daftarian, N and Kanav, MR and Ahmadieh, H and Sheibani, N},
title = {Intracellular Signaling Pathways and Their Potential Targeting for Treatment of Ocular Posterior Segment Fibrosis.},
journal = {Journal of ophthalmic &amp; vision research},
volume = {20},
number = {},
pages = {},
pmid = {40689128},
issn = {2008-2010},
abstract = {Treatment of posterior segment fibrosis is an unmet challenge in ophthalmology. Fibrotic responses complicate the pathology and treatment of age-related macular degeneration, diabetic retinopathy, retinal detachment, and other retinal diseases resulting in severe visual impairment. There is a lack of clear understanding of the exact mechanisms and different cell types taking part in retinal and preretinal fibrosis. This review discusses the current knowledge regarding various aspects of the intracellular signaling pathways impacting vitreoretinal fibrotic processes, focusing on the cellular and molecular mechanisms, summarizing the results of preclinical and clinical studies, and suggesting strategies for future investigations.},
}
@article {pmid40688787,
year = {2025},
author = {Yuan, LY and Su, WM and Li, LP and Tian, XF and Zheng, XL and Yuan, XY},
title = {Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study.},
journal = {International journal of ophthalmology},
volume = {18},
number = {7},
pages = {1307-1316},
pmid = {40688787},
issn = {2222-3959},
abstract = {AIM: To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration (AMD) phenotypes.<br><br>METHODS: A bidirectional Mendelian randomization (MR) analytical protocol was implemented, which utilized genome-wide association study (GWAS) summary statistics derived from the IEU OpenGWAS repositories. The investigation focused on 11 oxidative stress markers and AMD phenotypes, encompassing both wet and dry subtypes. The MR methodology incorporated inverse-variance weighted (IVW) calculations, MR-Egger statistical regression, weighted median approximation, and weighted mode assessments to estimate causative relationships. Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy.<br><br>RESULTS: Genetically predicted elevated catalase (CAT) concentrations demonstrated significant associations with heightened risks of overall AMD (IVW OR=1.084, 95%CI: 1.021-1.151, P=0.008) and wet AMD phenotype (IVW OR=1.113, 95%CI: 1.047-1.247, P=0.007). Higher genetically predicted albumin concentrations corresponded with reduced AMD risk (IVW OR=0.827, 95%CI: 0.715-0.957, P=0.013) but increased wet AMD risk (IVW OR=1.229, 95%CI: 1.036-1.458, P=0.018). Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels (IVW OR=0.987, 95%CI: 0.979-0.996, P=0.004), while wet AMD corresponded with decreased total bilirubin (TBIL) and paraoxonase (PON) activity.<br><br>CONCLUSION: The results offer strong support for a causal link between markers of oxidative stress and the development of AMD, indicating that oxidative processes play a role in driving the disease progression.},
}
@article {pmid40688783,
year = {2025},
author = {Jiang, YX and Gui, SY and Sun, XD},
title = {Associations between organophosphorus pesticides exposure and age-related macular degeneration risk in U.S. adults: analysis from interpretable machine learning approaches.},
journal = {International journal of ophthalmology},
volume = {18},
number = {7},
pages = {1214-1230},
pmid = {40688783},
issn = {2222-3959},
abstract = {AIM: To investigate the associations between urinary dialkyl phosphate (DAP) metabolites of organophosphorus pesticides (OPPs) exposure and age-related macular degeneration (AMD) risk.<br><br>METHODS: Participants were drawn from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008. Urinary DAP metabolites were used to construct a machine learning (ML) model for AMD prediction. Several interpretability pipelines, including permutation feature importance (PFI), partial dependence plot (PDP), and SHapley Additive exPlanations (SHAP) analyses were employed to analyze the influence from exposure features to prediction outcomes.<br><br>RESULTS: A total of 1845 participants were included and 137 were diagnosed with AMD. Receiver operating characteristic curve (ROC) analysis evaluated Random Forests (RF) as the best ML model with its optimal predictive performance among eleven models. PFI and SHAP analyses illustrated that DAP metabolites were of significant contribution weights in AMD risk prediction, higher than most of the socio-demographic covariates. Shapley values and waterfall plots of randomly selected AMD individuals emphasized the predictive capacity of ML with high accuracy and sensitivity in each case. The relationships and interactions visualized by graphical plots and supported by statistical measures demonstrated the indispensable impacts from six DAP metabolites to the prediction of AMD risk.<br><br>CONCLUSION: Urinary DAP metabolites of OPPs exposure are associated with AMD risk and ML algorithms show the excellent generalizability and differentiability in the course of AMD risk prediction.},
}
@article {pmid40687727,
year = {2025},
author = {Shao, Y and Lu, Y and Gu, Y and Chen, Y and Li, C},
title = {Natural active ingredients targeted inflammatory cytokines and major blinding eye diseases: a two-sample Mendelian randomization and molecular docking analysis.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1427144},
pmid = {40687727},
issn = {2296-858X},
abstract = {OBJECTIVES: Previous studies have reported that a few inflammatory cytokines have associations with ocular diseases. The objective of this study is to explore the causal relationship between 41 inflammatory cytokines and five ocular diseases using Mendelian randomization (MR) method and study the interaction between five natural active ingredients and inflammatory cytokines through molecular docking.<br><br>METHODS: The two-sample MR study employed genetic variances related to age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), myopia, and cataract. These variances were sourced from a comprehensive, publicly accessible genome-wide association study (GWAS). Additionally, inflammatory cytokines were derived from a GWAS summary that included 8,293 healthy individuals. The study primarily used the inverse variance weighted (IVW) method to investigate the causality between exposures and outcomes. To further bolster the final results, a variety of methods were concurrently used, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. A protein-protein interaction (PPI) network was constructed, and corresponding protein interaction relationships were analyzed utilizing the STRING database. Molecular docking served as an evaluation tool, confirming the binding between components and targets. This process was performed using AutoDock and PyMOL software.<br><br>RESULTS: The results indicated that IL-18 (OR: 1.134, 95% CI: 1.009-1.275, P = 0.034) and PDGF-BB (OR: 0.804, 95% CI: 0.678-0.954, P = 0.012) had protective effect on AMD; Genetically predicted RANTES had protective effect on glaucoma (OR: 0.886, 95% CI: 0.810-0.969, P = 0.008); IL-10 had protective effect on DR (OR: 0.871, 95% CI: 0.759-0.999, P = 0.048); GROa may be associated with increased myopia risk (OR: 1.230, 95% CI: 1.046-1.446, P = 0.012); Eotaxin (OR: 1.089, 95% CI: 1.018-1.165, P = 0.013), FGF2 (OR: 1.183, 95% CI: 1.004-1.393, P = 0.045) and GROa (OR: 1.053, 95% CI: 1.000-1.109, P = 0.049) were associated with increased cataract risk, while IL-1RA may be associated with decreased cataract risk. PPI network showed GROa, FGF2, IL-18, IL-1RA, IL-10, and Eotaxin interact closely. Molecular docking simulation showed that most of the compounds have good binding activities with critical targets.<br><br>CONCLUSION: The present study identified inflammatory cytokines with causal relationships to five ocular diseases, revealing potential compounds for treating these diseases, providing a theoretical basis for further clinical practice.},
}
@article {pmid40686765,
year = {2025},
author = {Micevych, PS and Fleckenstein, M and Bernstein, PS},
title = {Delayed-onset Moraxella nonliquefaciens endophthalmitis following intravitreal injection.},
journal = {American journal of ophthalmology case reports},
volume = {39},
number = {},
pages = {102370},
pmid = {40686765},
issn = {2451-9936},
abstract = {PURPOSE: To report a case of Moraxella nonliquefaciens endophthalmitis presenting one month after intravitreal injection.<br><br>OBSERVATIONS: An 84-year-old man presented to the retina clinic with vision loss, pain, and redness in his right eye 28 days after a routine intravitreal injection of faricimab for exudative age-related macular degeneration. The patient had a remote history of cataract surgery, rhegmatogenous retinal detachment repair, and scleral buckle explant for exposure 3 years prior. The patient was found to have endophthalmitis, characterized by a hypopyon and dense vitritis. Broad-spectrum intravitreal antimicrobials and dexamethasone were administered, and a vitreous tap returned sterile. The patient achieved initial quiescence, but he had two recurrences of inflammation in this eye over the next 4.5 months. The patient ultimately underwent pars plana vitrectomy, vitreous biopsy, intraocular lens explant, capsulectomy and repeat intravitreal antimicrobial injections for definitive treatment. Broad-range PCR testing detected Moraxella nonliquefaciens. Inflammation resolved after surgery without further recurrence in the subsequent 7-month post-operative period.<br><br>CONCLUSIONS AND IMPORTANCE: Moraxella species have been implicated in cases of endophthalmitis associated with glaucoma filtering surgery and trauma, but this report details a delayed-onset Moraxella nonliquefaciens-associated endophthalmitis after intravitreal injection.},
}
@article {pmid40686763,
year = {2025},
author = {Lam, WZ and Shen, M and Zhang, Q and Le, VH and Singla, K and Fooladi, MI and Jiang, H and Lam, BL and Wang, RK and Gregori, G and Rosenfeld, PJ},
title = {Longitudinal widefield OCT optic nerve thickness measurements in a case of incipient non-arteritic ischemic optic neuropathy.},
journal = {American journal of ophthalmology case reports},
volume = {39},
number = {},
pages = {102367},
pmid = {40686763},
issn = {2451-9936},
abstract = {PURPOSE: Widefield swept-source optical coherence tomography angiography (SS-OCTA) scans were combined with a semi-automated algorithm for the early detection and resolution of optic nerve edema in a case of incipient non-arteritic anterior ischemic optic neuropathy (NAION).<br><br>OBSERVATIONS: An incidental case of incipient NAION was identified in a 71-year-old woman enrolled in an ongoing prospective SS-OCTA imaging study using 12&#xa0;&#xd7;&#xa0;12 mm scans that allowed imaging of both the macular and optic disc regions of patients with age-related macular degeneration (AMD). Early intervention with systemic corticosteroids led to the resolution of optic disc edema without subsequent vision loss. A novel semi-automated algorithm was used to quantify the onset and resolution of optic nerve edema and edema in the surrounding retina.<br><br>CONCLUSIONS AND IMPORTANCE: This use of 12&#xa0;&#xd7;&#xa0;12 mm SS-OCTA scans and a semi-automated algorithm can significantly improve the detection and management of incipient NAION in clinical practice with the possibility that early detection would facilitate earlier intervention and better vision preservation in this condition. The use of widefield OCT imaging in conjunction with this novel algorithm in eyes at risk for optic nerve and macular edema could have broader implications for other retinal diseases in which optic disc and macular edema might arise such as diabetic retinopathy. Integrating this methodology into routine ophthalmic evaluations will enable clinicians to identify the onset of edema prior to vision loss, thereby improving patient outcomes.},
}
@article {pmid40684968,
year = {2025},
author = {Dhablania, N and Torres, M and Burkemper, B and McKean-Cowdin, R and Jiang, X and Varma, R and , },
title = {Burden and Predictors of Undetected Eye Disease in Adult African Americans: African American Eye Disease Study (AFEDS).},
journal = {American journal of ophthalmology},
volume = {279},
number = {},
pages = {91-99},
pmid = {40684968},
issn = {1879-1891},
support = {U10 EY023575/EY/NEI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Black or African American/statistics &amp; numerical data ; California/epidemiology ; Cross-Sectional Studies ; *Eye Diseases/ethnology/diagnosis ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; *Undiagnosed Diseases ; Visual Acuity/physiology ; },
abstract = {PURPOSE: To estimate the burden of and to evaluate the predictors associated with Undetected Eye Disease (UED) in African American adults.<br><br>DESIGN: Population-based cross-sectional study.<br><br>PARTICIPANTS: Self-identified African American participants 40 years and older (n = 6347) from thirty contiguous census tracts in Inglewood, California.<br><br>METHODS: Participants from the African American Eye Disease Study (AFEDS) underwent a complete ophthalmic examination and an in-home-administered questionnaire to assess predisposing, need, enabling, and health behavior predictors associated with UED, including an assessment of ocular conditions such as age-related macular degeneration (AMD), open-angle glaucoma, diabetic retinopathy (DR), visually-significant cataract, and refractive error. Participants with any eye disease (n = 3434) were included in these analyses. UED was defined as having 1 or more eye diseases (AMD, glaucoma, DR, visually-significant cataract-visual acuity in the cataractous less than 20/40, and refractive error) based on the eye examination and self-reporting no known history of any eye disease. The independent associations with UED were explored using multiple logistic regression analysis.<br><br>MAIN OUTCOMES AND MEASURES: Prevalence of and predisposing, need, enabling, and health behavior predictors of UED.<br><br>RESULTS: Fifty-four percent (3434 of 6347) of the participants had eye disease. Twenty-two percent (766 of 3434) of them had undetected eye disease. The major risk factors for UED included having diabetes mellitus (OR [95% CI], 3.52 [2.92-4.26], P < .0001), never having had an eye examination (OR [95% CI], 1.75 [1.14-2.65], P < .0001), having had an eye examination more than 5 years ago (OR [95% CI], 1.66 [1.19-2.31], P < .0001), having poor or very poor general vision (OR [95% CI], 1.89 [1.58-2.27], P < .0001), and trouble getting glasses (OR [95% CI], 1.57 [1.28-1.94], P < .0001).<br><br>CONCLUSIONS: Our data provides evidence of the significant burden of UED among African American individuals. Interventions that address the modifiable risk factors (e.g., trouble getting glasses, never having had an eye examination) may improve detection of eye disease and decrease the burden of VI in this high-risk minority population.},
}
@article {pmid40684186,
year = {2025},
author = {Guan, J and Meng, F and Wang, C and Zhang, B and Chen, J and Han, J},
title = {Recent advances in engineered exosome-based therapies for ocular vascular disease.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {526},
pmid = {40684186},
issn = {1477-3155},
support = {20230518//Natural Science Foundation of Liaoning Province/ ; CMU-A-025//China Medical University/ ; },
mesh = {*Exosomes/metabolism/chemistry ; Humans ; Animals ; Macular Degeneration/drug therapy ; Drug Delivery Systems ; *Eye Diseases/therapy ; Angiogenesis Inhibitors/therapeutic use ; Diabetic Retinopathy/drug therapy ; Neovascularization, Pathologic/drug therapy ; },
abstract = {Ocular neovascular diseases (ONDs), including corneal neovascularization (CoNV), age-related macular degeneration (AMD) and diabetic retinopathy (DR), are among the leading causes of visual impairment worldwide. Current therapeutic strategies predominantly involve intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents, which, despite their efficacy, present significant limitations such as drug resistance, frequent intravitreal injections, and insufficient addressing of underlying pathological mechanisms. This review critically examines recent advancements in the application of exosomes as innovative drug delivery platforms for treating ocular neovascular diseases. Exosomes, naturally occurring extracellular vesicles, exhibit superior biocompatibility, low immunogenicity, and intrinsic targeting capabilities, making them ideal carriers for bioactive molecules including proteins, RNAs, and small drugs. We explore the mechanistic roles of exosomes in modulating pathological angiogenesis, inflammation, and tissue repair within the ocular environment. Additionally, this review addresses the current challenges hindering the clinical translation of these exosomes, including large-scale production, regulatory hurdles, and safety concerns. Future perspectives highlight the potential integration of nanoparticles and exosomes with existing therapies, the development of multifunctional and personalized treatment strategies, and the necessity for standardized protocols to facilitate their transition from bench to bedside. By overcoming these challenges, exosomes hold the promise of revolutionizing the therapeutic landscape for ocular neovascular diseases, ultimately enhancing patient outcomes and quality of life.},
}
@article {pmid40684170,
year = {2025},
author = {Yan, C and Figueiredo, CA and Pompös, IM and Ugursu, B and Arribas-Lange, P and Skosyrski, S and Yang, S and Althoff, P and Kociok, N and Joussen, AM and Wolf, SA},
title = {Sex differences on laser-induced choroidal neovascularization and short-chain fatty acid treatment in a mouse model.},
journal = {Journal of neuroinflammation},
volume = {22},
number = {1},
pages = {188},
pmid = {40684170},
issn = {1742-2094},
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/etiology/pathology ; Female ; Mice ; Male ; Disease Models, Animal ; *Sex Characteristics ; Mice, Inbred C57BL ; *Lasers/adverse effects ; Microglia/drug effects/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a clinical presentation that varies between sexes. In late-stage AMD, choroidal neovascularization (CNV) triggers retinal inflammation and degeneration, processes that are exacerbated by an overactive response of retinal microglial cells. Short-chain fatty acids (SCFAs) have emerged as potential treatments for AMD due to their anti-inflammatory properties. In this study, we investigate the effects of SCFA treatment in a laser-induced CNV mouse model, focusing on sex-dependent differences in disease progression and microglial response. Our findings demonstrate distinct sex-specific patterns in the development of CNV and associated pathological hallmarks. SCFA treatment resulted in a slight increase in density of Iba1[+] microglial cells in females at 3 days post-laser (3dpl), while it prevented an increase in males at 7 dpl, with both sexes showing enhanced microglial ramification. The dynamics of microglial density were likely linked to protective effects on CNV lesion, leakage size, and inflammation, which occurred earlier in females and later in males. At transcriptional level, SCFA showed mixed effects, mainly targeting inflammation resolution, mitochondrial support, and neuronal repair in a sex-dependent manner. In vitro, SCFAs reduced microglial phagocytosis of retinal debris, suggesting a potential anti-inflammatory action. This study underscores the importance of considering sex-specific responses in the development of AMD treatments, such as SCFAs, and highlights the need for personalized therapeutic strategies.},
}
@article {pmid40684142,
year = {2025},
author = {Meng, Y and Tan, Z and Liu, Y and Ma, Y and Chen, Z and Jiang, L and Li, T},
title = {Association between life's crucial 9 and major eye diseases among US adults aged 40 years or older.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {2504},
pmid = {40684142},
issn = {1471-2458},
support = {82070972//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; United States/epidemiology ; Middle Aged ; *Eye Diseases/epidemiology ; Adult ; Nutrition Surveys ; Aged ; *Cardiovascular Diseases/epidemiology ; Risk Factors ; },
abstract = {BACKGROUND: Vision impairment due to eye diseases represents a significant global public health concern. There is an increasing acknowledgment of the relationship between cardiovascular health (CVH) and eye diseases. However, Life's Crucial 9 (LC9), the latest scoring framework for CVH, has yet to be investigated in relation to major eye diseases.<br><br>METHODS: This cross-sectional study included 3830 adults aged 40 years or older from the US National Health and Nutrition Examination Survey 2005-2008. We analyzed the relationship between LC9 scores and major eye diseases, including retinopathy, age-related macular degeneration, cataract, and glaucoma using weighted multivariable logistic regression, restricted cubic spline analysis, and subgroup analyses.<br><br>RESULTS: After adjusting for covariates, the poor CVH group (LC9&#x2009;<&#x2009;50) exhibited significant higher risks of glaucoma (odds ratio [OR]&#x2009;=&#x2009;2.37, 95% confidence interval [CI]: 1.11-5.08), retinopathy (OR&#x2009;=&#x2009;2.92, 95% CI: 1.84-4.63), and any objectively confirmed ocular disease (OR&#x2009;=&#x2009;2.25, 95% CI: 1.45-3.49) compared to the ideal CVH group (LC9&#x2009;&#x2265;&#x2009;80). Restricted cubic spline analysis demonstrated a significant inverse linear association between LC9 scores and the risk of these diseases. Subgroup analyses indicated significant interactions between LC9 score and sex concerning retinopathy and any objectively confirmed ocular disease.<br><br>CONCLUSIONS: Suboptimal CVH correlated with increased odds of several major eye diseases in adults aged 40 years or older, highlighting the potential value of CVH optimization for reducing visual impairment burden in this population. Further investigation on the potential causality is warranted.},
}
@article {pmid40684053,
year = {2025},
author = {Gurudas, S and Marques, I and Girmens, JF and Lechanteur, Y and Parravano, MC and Berger, L and Agostini, H and Barrão, S and Tsiroukis, E and Monés, J and Sararols, L and Silva, R and Scholl, H and Lommatzsch, A and Stanzel, B and Vujosevic, S and Sivaprasad, S and , },
title = {Visual acuity in various phenotypes of intermediate age related macular degeneration (AMD) in a multicentre cohort study in Europe- INTERCEPT-AMD report 1.},
journal = {Eye (London, England)},
volume = {39},
number = {14},
pages = {2655-2663},
pmid = {40684053},
issn = {1476-5454},
mesh = {Humans ; Male ; Female ; Aged ; *Visual Acuity/physiology ; *Macular Degeneration/physiopathology/classification ; Aged, 80 and over ; Europe/epidemiology ; Phenotype ; Retinal Pigment Epithelium/pathology ; Middle Aged ; Tomography, Optical Coherence ; Retinal Drusen/physiopathology ; },
abstract = {BACKGROUND/OBJECTIVES: To study the associations of VA and intermediate age-related macular degeneration (iAMD) subclassifications.<br><br>SUBJECTS/METHODS: This is the analysis of baseline data of a multicentre study on patients with iAMD in at least one eye. The subclassifications of iAMD were classified as: (i) iAMD with no evidence of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) or subretinal drusenoid deposits (SDD); (ii) iAMD with SDD with no iRORA; (iii) iAMD with iRORA with no SDD and (iv) iAMD with iRORA and SDD.<br><br>RESULTS: 983 eyes from 805 patients with iAMD were analysed. The mean age was 75.8 years (SD 7.9), with 35.0% (282) male. Eyes with iRORA with SDD had lower VA relative to eyes with no iRORA and no SDD (OR&#x2009;=&#x2009;0.98 [95% CI 0.96, 0.998]; P&#x2009;=&#x2009;0.03). The VA in the better seeing eye was significantly higher than in the worse seeing eye. Increased age (sex adjusted OR, 1.07, 95% CI 1.05-1.09; P&#x2009;<&#x2009;0.001) and female gender (age adjusted OR, 0.75, 95% CI 0.56-1.01; P&#x2009;=&#x2009;0.057) were associated with SDD. Eyes with nAMD in the fellow eye had reduced odds of iRORA in the study eye (adjusted OR&#x2009;=&#x2009;0.60, 95% CI 0.40-0.91; P&#x2009;=&#x2009;0.015). Eyes with GA had increased odds of iRORA in the study eye (adjusted OR&#x2009;=&#x2009;3.30, 95% CI 2.00-5.45; P&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Baseline age, presence of SDD and/or iRORA and fellow eye status need to be considered in future clinical trials evaluating preventive or treatment options for iAMD.},
}
@article {pmid40683606,
year = {2026},
author = {Jin, K and Yu, T and Grzybowski, A},
title = {Multimodal artificial intelligence in ophthalmology: Applications, challenges, and future directions.},
journal = {Survey of ophthalmology},
volume = {71},
number = {1},
pages = {158-167},
doi = {10.1016/j.survophthal.2025.07.003},
pmid = {40683606},
issn = {1879-3304},
mesh = {Humans ; *Artificial Intelligence/trends ; *Ophthalmology/trends/methods ; *Eye Diseases/diagnosis ; *Diagnostic Techniques, Ophthalmological ; },
abstract = {With the rapid development of artificial intelligence (AI) technology, multimodal AI that integrates multiple data modalities has shown tremendous potential in the field of ophthalmology. We systematically evaluate the current applications, technical characteristics, and clinical value of multimodal AI in ophthalmology. We conducted a systematic review following the PRISMA guidelines. We searched relevant literature published from 2018 to 2025 in PubMed, Web of Science, Scopus, and Google Scholar databases. A total of 10 studies were included in the final analysis. The main applications of multimodal AI in ophthalmology include glaucoma, age-related macular degeneration, corneal diseases, ophthalmic emergency triage, cognitive impairment screening, diabetes complication screening, and chatbot-based ophthalmic consultation. Multimodal systems showed superior performance compared to unimodal systems across various application areas, with an Area Under the Curve improvements of 4-5 % and accuracy improvements of 2-7 %. Multimodal AI demonstrates broad application prospects in ophthalmology, providing more comprehensive and accurate diagnostic information. Future research should focus on clinical validation, novel fusion methods, interpretability, and lightweight models to promote the clinical translation of multimodal AI in ophthalmology.},
}
@article {pmid40683364,
year = {2025},
author = {Liu, S and Liu, Y and Wu, X and Wang, H and Jin, Z and Wang, P and Feng, J and Chen, S and Zhou, W},
title = {Efficacy and prognostic factors of anti-VEGF treatment for neovascular age-related macular degeneration: An OCTA imaging-based deep learning analysis.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {55},
number = {},
pages = {104701},
doi = {10.1016/j.pdpdt.2025.104701},
pmid = {40683364},
issn = {1873-1597},
mesh = {Humans ; Female ; Male ; Aged ; Retrospective Studies ; *Deep Learning ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/drug effects ; Prognosis ; Aged, 80 and over ; *Macular Degeneration/drug therapy/diagnostic imaging ; Middle Aged ; Fluorescein Angiography/methods ; Intravitreal Injections ; },
abstract = {BACKGROUND: Anti-VEGF therapies improve visual acuity and reduce central macular thickness (CMT) in neovascular age-related macular degeneration(nAMD) patients. However, In our study, 35.76 % patients do not respond adequately to the anti-VEGF treatment.. Therefore, this study aimed to investigate imaging biomarkers and forecast the influencing factors of anti-VEGF treatment response in nAMD, aiming to enhance clinical evaluation.<br><br>METHODS: We retrospectively analyzed data from patients treated with anti-VEGF at Tianjin Medical University General Hospital from August 2018 to August 2023, including 165 patients with exudative AMD. We investigated their sex, age, best-corrected visual acuity (BCVA)(LogMAR), number of anti-VEGF treatments, optical coherence tomography angiography (OCTA) results. A deep learning model, the improved LUNet model was used to analyze OCTA images, focusing on retinal features including foveal avascular zone (FAZ), vessel density (VD), vessel diameter index (VDI), vessel dispersion (Vdisp) of retinal layers(deep vascular complex and deep vascular complex) to assess their relationship with treatment response.<br><br>RESULTS: After 6 months of anti-VEGF treatment, the patients' BCVA improved from 0.84 &#xb1; 0.40 to 0.70 &#xb1; 0.40 (t = 2.85, P = 0.005) (corresponds to an improvement from 20/140 to 20/100 on the Snellen scale.), CMT decreased from 300.16 &#xb1; 118.92 &#x3bc;m to 249.53 &#xb1; 84.39 &#x3bc;m (t = 4.46, P < 0.001). FAZ perimeter increased from 2.68 mm (2.29, 3.50) to 3.04 mm (2.57, 3.59) (Z=-2.05, P = 0.040), VDI decreased from 6.09 &#xb1; 0.83 to 5.90 &#xb1; 0.71 (t = 2.33, P = 0.021), central VD decreased (t = 2.21, P = 0.028). Logistic regression showed the Vdisp of macular neovascularization (Vdisp-MNV) (P = 0.007, OR 1.41), Vdisp of deep vascular complex(DVC) (P = 0.006, OR 0.45), neovascular surface area (SA) (P = 0.002, OR 0.26), and pigment epithelial detachment(PED) (P = 0.009, OR 0.29) significantly affected the response to anti-VEGF treatment. There were statistical differences in the association between the base line Vdisp of DVC (b = 0.07, t = 2.50, P = 0.014), base line intraretinal fluid (IRF) (b = 0.17, t = 2.02, P = 0.045) and base line BCVA, shown with multiple linear regression analysis.<br><br>CONCLUSION: This study analyzed factors affecting treatment response. Vdisp in MNV showed positive correlation with anti-VEGF treatment response; SA and PED showed negative correlation with anti-VEGF treatment response. It allowed for making personalized treatment strategy to tailor interventions based on individual risk profiles and vascular characteristics which can enhance patient outcomes.},
}
@article {pmid40682747,
year = {2025},
author = {Lupidi, M and Iaculli, C and Marco, L and Rossi, S and Sicari, E and Villa, G and Pirani, V},
title = {Faricimab in the Treatment of Exudative Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Italy: The FARIT Real World Study.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {9},
pages = {2197-2214},
pmid = {40682747},
issn = {2193-8245},
abstract = {INTRODUCTION: Faricimab is a bispecific antibody that enables greater disease control and extended durability compared with vascular endothelial growth factor (VEGF) inhibition alone in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). This study aimed to evaluate its effectiveness, durability, and economic and social burden in Italian clinical practice.<br><br>METHODS: FARIT was a retrospective, observational, multicenter cohort study across four Italian sites. Adult patients with nAMD or DME who initiated faricimab from February 2023 and had &#x2265;&#x2009;6&#xa0;months of follow-up were included. Clinical outcomes, treatment patterns, and patient-reported data were collected through chart review and electronic surveys.<br><br>RESULTS: A total of 87 eyes (68 with nAMD, 19 with DME) were followed for a median of 14&#xa0;months. Among them, 33 eyes (24 with nAMD, 9 with DME) were anti-VEGF na&#xef;ve. At 1&#xa0;year, 95.4% and 100% of na&#xef;ve eyes with nAMD and DME, respectively, reached a dosing interval of every 12&#xa0;weeks (Q12W) or longer; 63.6% and 100% received the treatment every 16&#xa0;weeks (Q16W). Among switch eyes, 92.4% (nAMD) and 71.5% (DME) reached &#x2265;&#x2009;Q12W, with 35.9% and 42.9%, respectively, on Q16W dosing. After a full loading phase, the median number of injections administered during the post-loading follow-up period (12&#xa0;months for nAMD, 10&#xa0;months for DME) was three for nAMD and two for DME. The interval extensions were driven by visual acuity stabilization/improvement and fluid resolution. Patients and caregivers reported high satisfaction and reduced burden, with fewer injections and better visual outcomes contributing most to improved quality of life. Economic analysis showed a 12-month direct cost (excluding the drug cost) of 1223.8 &#x20ac;/patient from the healthcare system perspective.<br><br>CONCLUSIONS: Faricimab provided effective disease control and extended treatment intervals in treatment-na&#xef;ve and previously treated eyes with nAMD and DME, showing a fast anatomical response and reduced injection burden.},
}
@article {pmid40682602,
year = {2025},
author = {Xie, B and Ding, L and Zhang, Q and Chen, X and Wang, K and Lv, J and Wang, J and Xiang, L and Qu, J and Chen, Q},
title = {Proteomic Signatures of Choroidal Neovascularization via Integrated LC-FAIMS-MS/MS Workflow.},
journal = {Journal of proteome research},
volume = {24},
number = {10},
pages = {5001-5010},
doi = {10.1021/acs.jproteome.5c00363},
pmid = {40682602},
issn = {1535-3907},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Tandem Mass Spectrometry/methods ; *Proteomics/methods ; Mice ; Chromatography, Liquid/methods ; Disease Models, Animal ; Workflow ; *Proteome/genetics ; Macular Degeneration/metabolism/pathology/genetics ; Protein Interaction Maps ; Retinal Pigment Epithelium/metabolism/pathology/chemistry ; Choroid/metabolism/pathology ; Mice, Inbred C57BL ; },
abstract = {The multicellular retinal pigment epithelium/choroid (RC) tissue is pivotal in maintaining retinal homeostasis and is closely associated with sight-threatening eye diseases. However, the limited sample amount, particularly in mice, poses a great challenge in comprehensively characterizing the functional proteins of the RC in disease models. This study utilized a state-of-the-art FAIMS device coupled with an Orbitrap Fusion Lumos mass spectrometer to systematically optimize the LC, FAIMS, and MS/MS acquisition parameters for in-depth proteomic analysis of the difficultly obtained RC samples. In a mouse model of neovascular age-related macular degeneration (nvAMD), the optimized workflow effectively increased the coverage of the proteome, which enabled the identification of 7047 proteins, compared to 5500 identified by conventional LC-MS/MS. Combined with multiomics data sets across species, differential expression analysis revealed 295 significantly altered proteins in the nvAMD model, including key regulators of extracellular matrix (ECM) remodeling (HTRA1, CCDC80) and immune response (SYK, CTSS). Functional enrichment and protein-protein interaction (PPI) network analysis highlighted critical pathways involved in neutrophil chemotaxis, ECM organization, and PI3K-Akt signaling, uncovering potential crosstalk between immune dysregulation and ECM degradation in choroidal neovascularization (CNV) progression. In conclusion, the optimized LC-FAIMS-MS/MS technique presented in this study offers an enhanced depth of proteomic analysis for the RC tissue, revealing novel insights into the molecular mechanisms of nvAMD and identifying new potential therapeutic targets.},
}
@article {pmid40682461,
year = {2025},
author = {Gurubaran, IS and Koskela, A and Heloterä, H and Kaarniranta, K},
title = {Secretory autophagy and epithelial-to-mesenchymal transition in cadaveric AMD samples: Novel pathways in disease progression.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.17558},
pmid = {40682461},
issn = {1755-3768},
support = {//the Sokeain Yst&#xe4;v&#xe4;t ry - De Blindas V&#xe4;nner sr/ ; //the Finnish Cultural Foundation/ ; //the Eye and Tissue Bank Foundation/ ; //the P&#xe4;ivikki and Sakari Sohlberg Foundation/ ; //the Sigrid Juselius Foundation/ ; //the Finnish Eye Foundation/ ; 5503770//the Kuopio University Hospital VTR grant/ ; 333302//the Academy of Finland/ ; },
abstract = {PURPOSE: To examine the presence of secretory autophagy and epithelial-mesenchymal transition (EMT) in the macular retinal pigment epithelium (RPE) of human cadaver eyes with different forms of age-related macular degeneration (AMD).<br><br>METHODS: Human cadaver macula samples representing dry and wet AMD, as well as age-matched controls, were analyzed using immunohistochemistry. Markers of secretory autophagy, EMT, and inflammation were evaluated in RPE cells.<br><br>RESULTS: Increased expression of proteins associated with secretory autophagy and EMT was detected in the RPE of AMD samples compared to controls. These changes were observed in both dry and wet AMD forms.<br><br>CONCLUSION: Secretory autophagy and EMT are elevated in the macular RPE of AMD-affected eyes. These observations offer novel insight into AMD progression and potential therapeutic approaches.},
}
@article {pmid40682000,
year = {2025},
author = {Edarous, DH and Fahim, HI and Momen, M and Shaat, AAE and Manzour, AF},
title = {Epidemiology of age-related macular degeneration among elderly in geriatric homes, East Cairo, Egypt.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {2495},
pmid = {40682000},
issn = {1471-2458},
abstract = {BACKGROUND: Visual impairment is one of the main causes of years lived with disability among adults 65 and older worldwide, according to the Global Burden of Disease Study (GBD). Both ageing and visual impairment are linked to an increased risk of falling, accounting for 40% of all injury-related deaths among older adults.<br><br>OBJECTIVE: To determine the prevalence of AMD among a sample of elderly residing in geriatric homes, identify associated factors of AMD, and to find out the effect of AMD on fall frequency in the studied group.<br><br>METHODS: A cross-sectional study was conducted on 283 elderly people in thirty geriatric homes in East Cairo. Data was collected using a structured interview questionnaire, and fundus examination for diagnosis.<br><br>RESULTS: The average age of study participants was 73.18&#x2009;&#xb1;&#x2009;7.09 (60&#x2013;96) years. AMD was present in 12.7% of the patients. Early AMD was present in 58.4% of AMD patients, whereas 8.3% and 33.3% of the participants had late dry and late wet AMD, respectively. Bilateral AMD was found in 38.9%, compared to 61.1% who had unilateral AMD. Compared to other age groups, the prevalence of AMD was significantly higher in people aging 75&#x2009;+&#x2009;years. About 47.2% of participants diagnosed with AMD were current smokers. Out of the participants diagnosed with AMD, 72.2% were diabetics and 91.7% were hypertensives. About 52.8% and 36.1% of AMD participants had moderate and high risk of fall according to the Morse Fall scale, respectively, while 52.7% and 30.6% of them had moderate and severe ADL impairment and scored below average in the IADL questionnaire compared to their normal peers.<br><br>CONCLUSION: The prevalence of AMD in Egypt is higher than previously documented. The most common form of AMD was early, and the late wet variety was second. Important non-modifiable risk factors for AMD include advancing age, being a woman, and having a positive family history of the disease. Additionally, smoking, diabetes, and hypertension are important risk factors for AMD. Vitamin A consumption appears to offer some protection against AMD. Compared to older adults without AMD, AMD patients had a higher risk of falls and more impairment in ADL and IADL.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-025-23680-6.},
}
@article {pmid40677744,
year = {2025},
author = {Alkhabaz, A and Kim, MY and Pujari, R and Zhang, J and Ren, Y and Leung, LB and Liao, YJ},
title = {Age-related macular degeneration associated with optic disc drusen.},
journal = {Frontiers in ophthalmology},
volume = {5},
number = {},
pages = {1620616},
pmid = {40677744},
issn = {2674-0826},
abstract = {OBJECTIVE: The aim of this study was to investigate the risk of age-related macular degeneration (AMD) in association with optic disc drusen (ODD).<br><br>DESIGN: This was an observational, cross-sectional study.<br><br>PARTICIPANTS: Participants were consecutive patients with and without ODD from the neuro-ophthalmology clinic. Ten patients with concomitant ODD-AMD were sub-analyzed.<br><br>METHODS: The two cohorts were identified from a prospectively recruited dataset between July 2022 and June 2024. Patients received formal diagnoses of ODD and AMD after ophthalmic and imaging assessment. A logistic regression model was utilized in calculating AMD risk to account for demographic differences.<br><br>RESULTS: A total of 94 patients with ODD (median age: 44 [Q1: 20, Q3: 69], 64% women) and 100 patients without ODD (median age: 60 [Q1: 44, Q3: 69], 48% women) were identified. AMD was observed in 9.6% and 3% of the ODD and non-ODD cohorts, respectively. The risk of AMD was higher in the ODD group (OR = 3.93, 95% CI: 0.89-21.85, p = 0.084). Although the association was not statistically significant, a logistic regression model attributed that to the age difference between the two cohorts. Of the 10 patients with ODD-AMD, 70% had a family history of AMD. These patients were all Caucasians and had a median age of 75 years (range: 56-91); 70% were women. Only 30% were smokers. On optic disc imaging, 70% of eyes demonstrated moderate-to-severe ODD.<br><br>CONCLUSION: Patients with ODD might be at a higher risk of AMD compared to patients without ODD, and AMD screening might be warranted. A family history of AMD is often present, indicating shared genetic risk factors.},
}
@article {pmid40676038,
year = {2025},
author = {Xie, H and Ye, Z and Chan, LLH},
title = {Optimizing electrical stimulation parameters to enhance visual cortex activation in retina degeneration rats.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {25918},
pmid = {40676038},
issn = {2045-2322},
support = {GHP/078/18GD//Innovation Technology Fund, Guangdong-Hong Kong Technology Cooperation Funding Scheme/ ; GHP/078/18GD//Innovation Technology Fund, Guangdong-Hong Kong Technology Cooperation Funding Scheme/ ; GHP/078/18GD//Innovation Technology Fund, Guangdong-Hong Kong Technology Cooperation Funding Scheme/ ; 2022-YF05-01360-SN//Chengdu Municipal Science and Technology Program/ ; 2022-YF05-01360-SN//Chengdu Municipal Science and Technology Program/ ; 11207419//Research Grants Council, University Grants Committee/ ; 11207419//Research Grants Council, University Grants Committee/ ; 7005452//City University of Hong Kong/ ; 7005452//City University of Hong Kong/ ; },
mesh = {Animals ; *Electric Stimulation/methods ; Rats, Long-Evans ; Rats ; *Retinal Degeneration/physiopathology/therapy ; Evoked Potentials, Visual/physiology ; *Visual Cortex/physiopathology ; Visual Prosthesis ; Disease Models, Animal ; Male ; Retina ; },
abstract = {In patients with degenerative retinal diseases such as retinitis pigmentosa and age-related macular degeneration, retinal prostheses offer a promising approach to restoring partial vision. Among these, epiretinal prostheses have shown encouraging preliminary clinical efficacy; however, optimizing stimulation parameters remains essential for improving efficiency and reducing power consumption. In this study, we investigated the effects of key electrical stimulation parameters- phase duration, frequency, and interphase interval (IPI) -on visual cortical electrically evoked potentials (EEPs) in both healthy Long-Evans (LE) rats and retinal degenerated (F1) rats. Our in vivo experiments on both LE and F1 rats revealed that shorter phase durations (500 µs) elicited activation in the primary visual cortex (V1) at lower charge thresholds. Our results also showed that responses to repetitive stimulation were significantly attenuated at high frequencies (10 and 20 Hz) compared to low frequency stimulation (1 Hz). Furthermore, we observed that longer phase durations (1000 and 1500 µs), as well as the inclusion of an IPI, resulted in a more confined spread of cortical activation. These findings suggest that adjusting phase duration can effectively reduce activation thresholds and spatially constrain cortical responses, and application of IPI can limit the extension of cortical responses, offering a potential strategy for enhancing the performance of epiretinal prostheses.},
}
@article {pmid40675433,
year = {2025},
author = {Tian, Y and Tang, R and Xie, M and Zhan, Y and Guo, Y and Zeng, X and Wang, S and Kuang, H and Yang, S and Gao, Z and Xiong, Z and Zhang, C and Dong, X and Li, X and Lu, W},
title = {SERPINB2 increases endothelial inflammation through augmented fatty acid oxidation to promote choroidal neovascularization.},
journal = {Experimental eye research},
volume = {259},
number = {},
pages = {110524},
doi = {10.1016/j.exer.2025.110524},
pmid = {40675433},
issn = {1096-0007},
mesh = {*Choroidal Neovascularization/metabolism/pathology ; Animals ; Humans ; *Fatty Acids/metabolism ; Oxidation-Reduction ; Disease Models, Animal ; *Inflammation/metabolism/pathology ; Mice, Inbred C57BL ; Mice ; *Plasminogen Activator Inhibitor 2/genetics ; Male ; Cells, Cultured ; Cell Proliferation ; Cell Movement ; *Endothelium, Vascular/metabolism/pathology ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly population, with choroidal neovascularization (CNV) being its key pathological feature. Endothelial cell (EC) inflammation plays a pivotal role in CNV progression. However, the crucial molecules regulating EC inflammation and the underlying mechanisms remain unclear. In this study, we found that Serine protease inhibitor family B member 2 (SERPINB2) is significantly upregulated in CNV and ECs during inflammation. SERPINB2 depletion by shRNA markedly reduced EC inflammation and neovascularization in a laser-induced CNV model. SERPINB2 knockdown inhibited EC proliferation, migration, and tube formation, as well as the recruitment and transendothelial migration of monocytes. Mechanistically, SERPINB2 depletion reduced the expression of fatty acid oxidation (FAO)-related genes, such as CPT1C, resulting in lipid accumulation and decreased FAO activity in ECs. ETO (an FAO inhibitor) treatment impaired EC functions, whereas supplementation with fatty acid octanoate rescued EC dysfunction caused by SERPINB2 knockdown. Importantly, delivery of AAV-mediated EC-specific shSerpinb2 or ETO treatment markedly inhibited CNV and inflammation in vivo. Collectively, our findings revealed that SERPINB2 promotes CNV by driving EC inflammation through increased FAO. Targeting SERPINB2/FAO may offer a new promising therapeutic strategy for nAMD treatment.},
}
@article {pmid40673740,
year = {2025},
author = {Curcio, CA and Mullins, RF and Stone, EM and Goerdt, L and Kar, D and Gao, L and McGwin, G and Owsley, C},
title = {Genetic Associations of Rod- and Cone-Mediated Vision in Aging and Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {9},
pages = {50},
pmid = {40673740},
issn = {1552-5783},
support = {UL1 TR003096/TR/NCATS NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; R01 AG004212/AG/NIA NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY026087/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/genetics/physiopathology ; Aged ; Male ; Female ; Middle Aged ; *Polymorphism, Single Nucleotide ; Complement Factor H/genetics ; *Dark Adaptation/physiology/genetics ; *Aging/physiology/genetics ; *Retinal Cone Photoreceptor Cells/physiology ; *Retinal Rod Photoreceptor Cells/physiology ; Visual Acuity/physiology ; *Proteins/genetics ; Aged, 80 and over ; },
abstract = {PURPOSE: To compare genetic associations of rod- and cone-driven vision with those previously defined for delayed rod-mediated dark adaptation (RMDA), a functional risk indicator for incident age-related macular degeneration (AMD).<br><br>METHODS: In adults aged &#x2265;60 years with two normal eyes (per the Age-Related Eye Disease Study 9-step scale) or with AMD in one or both eyes, we measured RMDA at 5&#xb0; superior retina, photopic vision (acuity, contrast sensitivity, light sensitivity), and mesopic vision (low luminance acuity and deficit). Vision associations of risk-conferring single-nucleotide polymorphisms in CFH and ARMS2 genes were adjusted for age and smoking and stratified for the presence of subretinal drusenoid deposit (SDD).<br><br>RESULTS: Of 608 participants, 462 had normal maculas and 146 had AMD. Neither ARMS2 nor CFH was significantly associated with AMD stage. Across all eyes, RMDA worsened significantly in association with ARMS2 (P = 0.0005). Associations were stronger in normal eyes than in AMD (P = 0.0012 vs. 0.0580) and in normal eyes lacking SDD (n = 384, P < 0.0024). Across all eyes, RMDA was significantly associated with CFH (P = 0.0023) but not in normal and AMD eyes separately (P = 0.270 vs. 0.0596). RMDA was significantly associated with the number of risk alleles in normal and AMD eyes (P < 0.0001). Low luminance deficit was associated with gene dose for AMD eyes only (P = 0.477).<br><br>CONCLUSIONS: Of six vision tests, only RMDA was consistently associated with major risk alleles, including ARMS2 (not CFH) in normal eyes, with or without SDD. RMDA assesses dynamic retinoid resupply from the circulation, perhaps presaging SDD. Results are interpreted considering localization of key proteins in Bruch's membrane.},
}
@article {pmid40672824,
year = {2025},
author = {Umair, M and Ahmad, J and Saidani, O and Alshehri, MS and Al Mazroa, A and Hanif, M and Ullah, R and Khan, MS},
title = {OculusNet: Detection of retinal diseases using a tailored web-deployed neural network and saliency maps for explainable AI.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1596726},
pmid = {40672824},
issn = {2296-858X},
abstract = {Retinal diseases are among the leading causes of blindness worldwide, requiring early detection for effective treatment. Manual interpretation of ophthalmic imaging, such as optical coherence tomography (OCT), is traditionally time-consuming, prone to inconsistencies, and requires specialized expertise in ophthalmology. This study introduces OculusNet, an efficient and explainable deep learning (DL) approach for detecting retinal diseases using OCT images. The proposed method is specifically tailored for complex medical image patterns in OCTs to identify retinal disorders, such as choroidal neovascularization (CNV), diabetic macular edema (DME), and age-related macular degeneration characterized by drusen. The model benefits from Saliency Map visualization, an Explainable AI (XAI) technique, to interpret and explain how it reaches conclusions when identifying retinal disorders. Furthermore, the proposed model is deployed on a web page, allowing users to upload retinal OCT images and receive instant detection results. This deployment demonstrates significant potential for integration into ophthalmic departments, enhancing diagnostic accuracy and efficiency. In addition, to ensure an equitable comparison, a transfer learning approach has been applied to four pre-trained models: VGG19, MobileNetV2, VGG16, and DenseNet-121. Extensive evaluation reveals that the proposed OculusNet model achieves a test accuracy of 95.48% and a validation accuracy of 98.59%, outperforming all other models in comparison. Moreover, to assess the proposed model's reliability and generalizability, the Matthews Correlation Coefficient and Cohen's Kappa Coefficient have been computed, validating that the model can be applied in practical clinical settings to unseen data.},
}
@article {pmid40671998,
year = {2025},
author = {Sato, S and Sakurada, Y and Fukuda, Y and Kotoda, Y and Kashiwagi, K},
title = {Recurrence of Intraocular Inflammation Following an Aflibercept 8-mg Injection in Eyes With a History of Intraocular Inflammation From Faricimab: A Case Report.},
journal = {Cureus},
volume = {17},
number = {6},
pages = {e86113},
pmid = {40671998},
issn = {2168-8184},
abstract = {Vascular endothelial growth factor (VEGF) is critical in various retinal diseases. VEGF inhibitors are a standard treatment for neovascular age-related macular degeneration (AMD). However, intraocular inflammation (IOI) is a major complication after intravitreal administration of second-generation VEGF inhibitors. We report a case of IOI following treatment with aflibercept 8 mg in an eye with a history of IOI due to faricimab. An 83-year-old man was referred to our clinic and diagnosed with type 1 macular neovascularization (MNV), with a previous treatment history of four doses of ranibizumab, 14 doses of aflibercept (2 mg), and two doses of faricimab. The best-corrected visual acuity (BCVA) in the right eye was 0.3 in the decimal format. Treatment was initiated with an as-needed faricimab regimen after three consecutive monthly injections. Thirteen days after the ninth faricimab injection, the patient complained of blurred vision in the right eye. Mild inflammation, with small keratic precipitates (KPs), was observed in the anterior chamber. After topical dexamethasone administration (four times a day), the anterior chamber inflammation resolved one week after treatment. However, exudation recurred 13 weeks after the ninth faricimab administration; therefore, the intravitreal injection was switched to aflibercept 8 mg. Two days after switching to aflibercept 8 mg, the patient complained of pain and blurred vision in the right eye. As with the ninth faricimab injection, mild inflammation was observed in the anterior chamber of the right eye. One week after subtenon triamcinolone acetonide (STTA) and topical dexamethasone, inflammation disappeared in the anterior chamber. In eyes with a history of IOI, careful attention is needed when switching to aflibercept 8 mg from another second-generation VEGF inhibitor, including faricimab.},
}
@article {pmid40671118,
year = {2025},
author = {Shippy, DC and Ulland, TK},
title = {Verteporfin attenuates NLRP3 inflammasome activation to alleviate gout arthritis flares.},
journal = {Journal of inflammation (London, England)},
volume = {22},
number = {1},
pages = {28},
pmid = {40671118},
issn = {1476-9255},
support = {R01 AG083883/AG/NIA NIH HHS/United States ; Early-Career Investigator Award//William F. Vilas Trust Estate/ ; R01AG083883/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Gout arthritis (GA) is an inflammatory disorder characterized by the deposition of monosodium urate (MSU) crystals within synovial joints due to increased urate concentrations in the body. The NLRP3 inflammasome drives a majority of the inflammatory response to MSU crystals; therefore, we hypothesize pharmaceutical agents that attenuate NLRP3 inflammasome activation could be used to treat GA flares.<br><br>RESULTS: We screened a drug library containing 875 FDA-approved drugs and identified five drugs that reduced NLRP3 inflammasome activation without causing cytotoxic effects in bone marrow-derived macrophages (BMDM). The best performing and therefore leading candidate, verteporfin, used to treat macular degeneration and other eye disorders, reduced Nlrp3- and Caspase-1-dependent IL-1&#x3b2; and IL-18 secretion by BMDM. Additionally, verteporfin-treated mice showed a marked reduction in paw swelling and pro-inflammatory cytokine/chemokine induction, including inflammasome markers (IL-1&#x3b2; and IL-18), in a MSU-induced mouse model of GA flares.<br><br>CONCLUSION: Collectively, these data suggest verteporfin is a NLRP3 inflammasome inhibitor that could be repurposed as a treatment for GA.},
}
@article {pmid40670757,
year = {2025},
author = {Zou, R and Zhang, X and Dai, X and Yuan, Y and Dai, J and Yuan, F},
title = {The SDF-1α/MTDH axis inhibits ferroptosis and promotes the formation of anti-VEGF-resistant choroidal neovascularization by facilitating the nuclear translocation of SREBP1.},
journal = {Cell biology and toxicology},
volume = {41},
number = {1},
pages = {118},
pmid = {40670757},
issn = {1573-6822},
support = {82201181//National Natural Science Foundations of China/ ; 3502Z20227277//Xiamen Municipal Bureau of Science and Technology/ ; 24ZR1411400//Science and Technology Commission of Shanghai Municipality/ ; },
mesh = {*Sterol Regulatory Element Binding Protein 1/metabolism ; Animals ; *Chemokine CXCL12/metabolism ; Mice ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Humans ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; *Ferroptosis/drug effects ; Ranibizumab/pharmacology ; RNA-Binding Proteins/metabolism ; Mice, Inbred C57BL ; Endoplasmic Reticulum/metabolism ; Membrane Proteins/metabolism ; Macular Degeneration/drug therapy/metabolism ; Golgi Apparatus/metabolism ; Cell Nucleus/metabolism ; },
abstract = {Age-related macular degeneration (AMD) has been well recognized as the first ranked blinding ocular fundus diseases among older individuals, particularly in developed regions, owing to its progressive nature and high prevalence in aging populations. Anti-vascular endothelial growth factor (VEGF) agents injected into patients' vitreous cavity is the preferred treatment regimen for neovascular AMD. However, many patients exhibit resistance to anti-VEGF treatment, which is an urgent clinical problem. In this study, we treated mouse and endothelial cells with anti-VEGF drug Ranibizumab and stromal cell-derived factor-1α (SDF-1α) and found that ferroptosis was induced by Ranibizumab but inhibited by SDF-1α. SDF-1α inhibited ferroptosis by promoting transport of Sterol regulatory element binding protein 1 (SREBP1) from endoplasmic reticulum (ER) to Golgi transportation and SREBP1 maturation. Furthermore, we found that metadherin (MTDH) mediates SREBP1' s movement from the endoplasmic reticulum (ER) to Golgi apparatus by inhibiting SREBP1 binding to INSIG1/INSIG2. Our study revealed the important role of SDF-1α/MTDH/SREBP1 axis in regulating anti-VEGF treatment resistance in patients with AMD.},
}
@article {pmid40669451,
year = {2025},
author = {Marques, IP and Almeida, AC and Futterknecht, S and Hatz, K and Cunha-Vaz, J and Scholl, HPN and Lobo, C and Silva, R and Murta, JN and Anders, P and Anders, LM and Santos, AR and Pfau, M},
title = {Association of Localized Retinal Sensitivities with Spectral-Domain Optical Coherence Tomography-Derived Morphologic Data in Macular Subfields in Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {68},
number = {1},
pages = {389-399},
pmid = {40669451},
issn = {1423-0259},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; Aged ; Male ; Female ; *Macular Degeneration/physiopathology/diagnosis ; Visual Field Tests/methods ; *Visual Fields/physiology ; *Visual Acuity/physiology ; *Macula Lutea/pathology/physiopathology ; Aged, 80 and over ; *Retina/physiopathology ; },
abstract = {INTRODUCTION: This study investigated microperimetry-derived retinal sensitivity and optical coherence tomography (OCT)-based macular morphologic data in eyes with early and intermediate age-related macular degeneration (AMD). The respective metrics were compared between macular subfields and their associations were determined. Detailed knowledge of functional associations with morphology is an asset to future therapeutic trial design.<br><br>METHODS: This is a cross-sectional analysis of microperimetry and spectral-domain OCT baseline data. OCT data were segmented automatically within the HEYEX software (Heidelberg Engineering). Data were assessed for Gaussian normal distribution by the D'Agostino and Pearson tests, and appropriate comparison tests were performed for parametric and nonparametric data. The association of retinal sensitivity metrics with OCT morphologic data was tested with mixed-effects models.<br><br>RESULTS: In total, 19 eyes of 19 participants (75 &#xb1; 6.4 years) with early and intermediate AMD were included in the analysis. Both in mesopic (p < 0.05) and in scotopic red (p < 0.001) microperimetry, retinal sensitivities differed significantly between macular subfields in ANOVA. Nasal and temporal subfields showed the highest retinal sensitivities, also compared to the central subfield. Generally, subfields within the 1 mm-2 mm diameter ring showed higher retinal sensitivities than subfields within the 2 mm-3 mm diameter ring. Superior subfields demonstrated higher retinal sensitivity than inferior subfields in mesopic microperimetry. RPE thickness was mostly negatively associated with retinal sensitivity, which was pronounced in the ETDRS inner ring inferior subfield and for mesopic retinal sensitivity (t value, p value: -3.7, <0.01). In the center position, inner retinal thickness was negatively associated with mesopic retinal sensitivity (t value, p value: -2.2, <0.05).<br><br>CONCLUSION: Retinal layer thicknesses and their associations with retinal sensitivity show localized differences between macular subfields in early and intermediated AMD. An analysis including more subjects is necessary to confirm these trends. This knowledge is of importance since therapeutic trial design requires detailed morphologic but also functional conception in order to detect therapeutic effects and pass regulatory hurdles.},
}
@article {pmid40668583,
year = {2025},
author = {Chen, Q and Keenan, TDL and Agron, E and Allot, A and Guan, E and Duong, B and Elsawy, A and Hou, B and Xue, C and Bhandari, S and Broadhead, G and Cousineau-Krieger, C and Davis, E and Gensheimer, WG and Golshani, CA and Grasic, D and Gupta, S and Haddock, L and Konstantinou, E and Lamba, T and Maiberger, M and Mantopoulos, D and Mehta, MC and Elnahry, AG and Al-Nawaflh, M and Oshinsky, A and Powell, BE and Purt, B and Shin, S and Stiefel, H and Thavikulwat, AT and Wroblewski, KJ and Tham, YC and Cheung, CMG and Cheng, CY and Chew, EY and Hribar, MR and Chiang, MF and Lu, Z},
title = {AI Workflow, External Validation, and Development in Eye Disease Diagnosis.},
journal = {JAMA network open},
volume = {8},
number = {7},
pages = {e2517204},
pmid = {40668583},
issn = {2574-3805},
support = {R00 LM014024/LM/NLM NIH HHS/United States ; },
mesh = {Humans ; *Artificial Intelligence ; *Workflow ; *Macular Degeneration/diagnosis/classification ; Female ; Male ; Aged ; *Eye Diseases/diagnosis ; Reproducibility of Results ; Middle Aged ; },
abstract = {IMPORTANCE: Timely disease diagnosis is challenging due to limited clinical availability and growing burdens. Although artificial intelligence (AI) has shown expert-level diagnostic accuracy, a lack of downstream accountability, including workflow integration, external validation, and further development, continues to hinder its clinical adoption.<br><br>OBJECTIVE: To address gaps in the downstream accountability of medical AI through a case study on age-related macular degeneration (AMD) diagnosis and severity classification.<br><br>This diagnostic study developed and evaluated an AI-assisted diagnostic and classification workflow for AMD. Four rounds of diagnostic assessments (accuracy and time) were conducted with 24 clinicians from 12 institutions. Each round was randomized and alternated between manual (clinician diagnosis) and manual plus AI (clinician assisted by AI diagnosis), with a 1-month washout period. In total, 2880 AMD risk features were evaluated across 960 images from 240 Age-Related Eye Disease Study patient samples, both with and without AI assistance. For further development, the original DeepSeeNet model was enhanced into the DeepSeeNet+&#x2009;model using&#x2009;39 196 additional images from the US population and tested on 3 datasets, including an external set from Singapore.<br><br>EXPOSURE: Age-related macular degeneration risk features.<br><br>MAIN OUTCOMES AND MEASURES: The F1 score for accuracy (Wilcoxon rank sum test) and diagnostic time (linear mixed-effects model) were measured, comparing manual vs manual plus AI. For further development, the F1 score (Wilcoxon rank sum test) was again used.<br><br>RESULTS: Among 240 patients (mean [SD] age, 68.5 [5.0] years; 127 female [53%]), AI assistance significantly improved accuracy for 23 of 24 clinicians, increasing the mean F1 score from 37.71 (95% CI, 27.83-44.17) to 45.52 (95% CI, 39.01-51.61), with some improvements exceeding 50%. Manual diagnosis initially took an estimated 39.8 seconds (95% CI, 34.1-45.6 seconds) per patient, whereas manual plus AI saved 10.3 seconds (95% CI, -15.1 to -5.5 seconds) and remained faster by 6.9 seconds (95% CI, 0.2-13.7 seconds) to 8.6 seconds (95% CI, 1.8-15.3 seconds) in subsequent rounds. However, combining manual and AI did not always yield the highest accuracy or efficiency, underscoring challenges in explainability and trust. The DeepSeeNet+&#x2009;model performed better in 3 test sets, achieving a significantly higher F1 score than the Singapore cohort (52.43 [95% CI, 44.38-61.00] vs 38.95 [95% CI, 30.50-47.45]).<br><br>CONCLUSIONS AND RELEVANCE: In this diagnostic study, AI assistance was associated with improved accuracy and time efficiency for AMD diagnosis. Further development is essential for enhancing AI generalizability across diverse populations. These findings highlight the need for downstream accountability during early-stage clinical evaluations of medical AI.},
}
@article {pmid40668050,
year = {2025},
author = {Heine, L and Vahldiek, A and Vahldiek, B and Hörst, F and Seibold, C and Lever, M and Pauleikhoff, L and Bechrakis, N and Pauleikhoff, D and Kleesiek, J},
title = {Three-Dimensional Quantification of Macular OCT Alterations Improves the Diagnostic Performance of Artificial Intelligence Models.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {7},
pages = {8},
pmid = {40668050},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Artificial Intelligence ; *Imaging, Three-Dimensional/methods ; *Macular Degeneration/diagnostic imaging ; Aged ; *Macula Lutea/diagnostic imaging/pathology ; Female ; Male ; *Wet Macular Degeneration/diagnostic imaging ; },
abstract = {PURPOSE: To evaluate the performance of state-of-the-art semantic segmentation methods on OCT data for age-related macular degeneration (AMD). We measured variability between annotators to quantify differences in ground truth arising from personal bias.<br><br>METHODS: From 94 patients suffering from exudative neovascular AMD (nAMD), 24 volume scans (49 slices each) were selected. Trained members of a reading center for AMD created pixel-wise masks for 12 retinal layers and two pathological labels (fluid, hyperreflective material) to benchmark two-dimensional (2D) and three-dimensional (3D) segmentation models on clinical data. Models were evaluated using fivefold cross-validation, and the best model was used to quantify errors between ground truth and predictions.<br><br>RESULTS: The nnU-Net (3D) achieves the best segmentation performance (mean Dice similarity coefficient [DSC] of 0.907), leaving a theoretical gap of 0.036 DSC to the mean interrater agreement, which is the upper bound of model performances. Comparing the volumes calculated for each structure using the model masks with the ground truth produced an average error of 0.065&#xa0;mm3.<br><br>CONCLUSIONS: Models like nnU-Net can produce high-quality 3D masks, challenging the conventional reliance on 2D slices for optimal performance. Both DSC and low average errors indicate that such a model is fit for the large-scale analysis of cohorts.<br><br>TRANSLATIONAL RELEVANCE: The presented approach can streamline clinical workflows by reducing the time and effort required for manual annotations, ultimately supporting more efficient and accurate monitoring of AMD progression and treatment response. We provide open-source access to the model weights, annotation instructions and sample data.},
}
@article {pmid40667189,
year = {2025},
author = {Li, J and Wang, T and Lu, W and Jishkariani, D and Tsourkas, A and Kaja, S and Nair, RM and Dunaief, JL and Mitchell, CH},
title = {Sustained Lysosomal Delivery of Enhanced Cy3-Labeled Acid Nanoparticles Restores Lysosomal pH in Retinal Pigment Epithelial Cells and Astrocytes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40667189},
issn = {2692-8205},
support = {R01 EY013434/EY/NEI NIH HHS/United States ; R01 EY015537/EY/NEI NIH HHS/United States ; },
abstract = {Lysosomal pH is frequently elevated in age-dependent neurodegenerations like Age-related Macular Degeneration (AMD), Alzheimer's Disease (AD), and Parkinson's Disease (PD). Tools that restore lysosomal pH to an optimal acidic range could enhance enzymatic degradation and reduce waste accumulation. Acidic nanoparticles offer a promising strategy for restoring lysosomal function, but accurate tracking of organelle delivery and long-term retention is needed to optimize dosage. To improve detection and enhance delivery, nanoparticles were synthesized from Poly(D,L-lactide-co-glycolide) (PLGA) polymers covalently linked to the fluorescent Cyanine3 amine (Cy3) probe. Nanoparticle concentration and loading times were optimized to achieve >90% delivery to lysosomes in cultured induced pluripotent stem cell-derived retinal pigment epithelial (iPS-RPE) cells. Uptake was heterogeneous, varying between adjacent cells. Once loaded into lysosomes, the nanoparticles were stably retained, with no detectable changes in concentration, distribution, or size for at least 28 days. iPS-RPE cells internalized more nanoparticles than the ARPE-19 cell line or mouse optic nerve head astrocyte cultures. Functionally, PLGA nanoparticles restored an acidic pH and cathepsin D levels in compromised lysosomes. In summary, Cy3-PLGA nanoparticles enabled improved tracking and long-term delivery to lysosomes, supporting future in vivo applications to restore lysosomal pH in aging and degenerating tissues.},
}
@article {pmid40666756,
year = {2025},
author = {Bhattacharya, A and Majumdar, S and Ray, MS and Nandi, D and Ghosh, S and Banerjee, D},
title = {A comparative study of retinal vein occlusion and serum 25 hydroxy Vitamin D at a tertiary care centre.},
journal = {Oman journal of ophthalmology},
volume = {18},
number = {2},
pages = {182-186},
pmid = {40666756},
issn = {0974-620X},
abstract = {BACKGROUND: Prevalence of retinal vascular occlusion is second to diabetic retinopathy and age-related macular degeneration. Various age-related local and systemic factors have been associated with retinal vein occlusion (RVO). Hemodynamic changes (venous stasis), degenerative changes of the vessel wall and blood hypercoagulability underlies the pathogenesis. The role of Vitamin D in modulating the inflammatory responses within the arterial wall, the capacity to attenuate the oxidative stress and direct effect of hypovitaminosis D on increased vascular resistance hints at a potential association of Vitamin D levels with disorders of retinal vasculature.<br><br>AIM: To estimate serum 25-hydroxyvitamin D (25 OH Vit D) level in patients of RVO and compare it with matched controls.<br><br>MATERIALS AND METHODS: Fifty patients of RVO as cases and 50 without RVO as controls underwent systemic and ocular examination including the estimation of serum 25 OH Vit D and other biochemical parameters.<br><br>STATISTICAL ANALYSIS: Statistical Package for the Social Sciences (SPSS) software version 25 was used for the analysis. An alpha level of 5% was taken, that is P < 0.05 was considered statistically significant.<br><br>RESULTS: Mean serum 25 OH Vit D level in cases of RVO was 21.82 nanogram/deciliters (ng/dL) compared to 30.71 ng/dL in the control group which was significantly lower in cases compared to control (P < 0.001). The odds ratio calculated for RVO cases versus controls was 1.137; 95% confidence interval (1.074-1.203).<br><br>CONCLUSION: A positive association of low serum 25 OH Vit D levels and RVO was found highlighting the importance of evaluating serum Vitamin D levels in all the cases of RVO. This correlation may have possible implications for prophylaxis and treatment of RVO, even though this part of our country gets abundant sunlight throughout the year.},
}
@article {pmid40666342,
year = {2025},
author = {Green, DJ and Romero-Bascones, D and Julian, TH and Torchia, S and Joisher, HNV and , and Ayala, U and Barrenechea, M and Self, JE and Black, GC and Fitzgerald, T and Birney, E and Cepko, CL and Carroll, J and Sergouniotis, PI},
title = {Genetic insights into foveal morphology and its associations with pigmentation and age-related macular degeneration.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40666342},
support = {/WT_/Wellcome Trust/United Kingdom ; R01 EY017607/EY/NEI NIH HHS/United States ; R01 EY033580/EY/NEI NIH HHS/United States ; },
abstract = {The fovea is the small depression at the neurosensory retina that underlies high-resolution central vision. It is vulnerable to disease and disruption of its architecture causes visual disability. Foveal morphology varies significantly across individuals. The molecular causes and functional consequences of this anatomical diversity are incompletely understood. Here, we extracted six foveal morphological parameters from Optical Coherence Tomography (OCT) images of 55,604 UK Biobank participants. We found notable variability in foveal morphology, and detected significant links with sex and genetic ancestry. Genome-wide association studies identified 197 lead loci across the six foveal morphological parameters, implicating genes involved in pigmentation (e.g., TYR, TSPAN10, GPR143) and patterning (e.g., FGFR2, PTPRD, CYP1A1). Heritability estimates ranged from 29-43%. Foveal pit volume was associated with future risk of age-related macular degeneration (HR>3.5, p=0.001), a finding supported by Mendelian randomization. These results establish foveal morphology as a highly-heritable trait with substantial influence over retinal disease risk.},
}
@article {pmid40665980,
year = {2025},
author = {Peng, B and Mu, J and Xu, F and Guo, W and Sun, C and Fan, W},
title = {Artificial intelligence in ophthalmology: a bibliometric analysis of the 5-year trends in literature.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1580583},
pmid = {40665980},
issn = {2296-858X},
abstract = {PURPOSE: This study aims to generate and elucidate the latest perspectives on the application of artificial intelligence (AI) in ophthalmology using bibliometric methods. By analyzing literature from the past 5 years (2020-2024), we seek to outline the development trends of this technology, provide guidance for its future directions, and assist clinicians in adapting to these innovations.<br><br>METHODS: We conducted a comprehensive search of all literature related to AI and ophthalmology in the Web of Science Core Collection (WoSCC) using bibliometric methods. The collected data were analyzed and visualized using three widely recognized bibliometric software tools: CiteSpace, VOSviewer, and the R package "Bibliometrix."<br><br>RESULTS: A total of 21,725 documents were included from 134 countries and 7,126 institutions, consisting of 19,978 articles (91.96%) and 1,714 reviews (8.04%), with China and the United States leading the contributions. The number of publications in AI and ophthalmology has increased annually, with the University of California System, the National University of Singapore, and the University of London being the primary research institutions. Ophthalmology and Proc CVPR IEEE are the most co-cited journals and conferences in this field. These papers were authored by 87,695 individuals, with Wang Y, Liu Y, and Zhang Y the most prolific authors. Ting DSW was the most co-cited author. Major research topics include using various models to scan retinal images for diagnosing conditions such as age-related macular degeneration, diabetic retinopathy, and retinal nerve fiber layer thinning caused by glaucoma. The intersection of AI with other subfields of ophthalmology, such as in the diagnosis of ametropia, strabismus, eyelid disease, and orbital tumors, as well as in postoperative follow-up, is also rapidly developing. Key research hot spots are identified by keywords such as "deep learning," "machine learning," "convolutional neural network," "diabetic retinopathy," and "ophthalmology."<br><br>CONCLUSION: Our bibliometric analysis outlines the dynamic evolution and structural relationships within the AI and ophthalmology field. In contrast to previous studies, our research transcends individual domains to offer a more comprehensive insight. Notably, our analysis encompasses literature published beyond the year 2022, a pivotal year marking both the post-pandemic era and the rapid advancement of AI technologies. This temporal scope potentially fills a gap that prior bibliometric studies have not addressed. This information identifies recent research frontiers and hot spot areas, providing valuable reference points for scholars engaging in future AI and ophthalmology studies.},
}
@article {pmid40664762,
year = {2025},
author = {Hapeshi, J and Hughes, S and McKibbin, M and Scanlon, PH},
title = {A thematic analysis of patients' experiences of receiving treatment for Neovascular age-related macular degeneration (nAMD).},
journal = {Eye (London, England)},
volume = {39},
number = {13},
pages = {2565-2569},
pmid = {40664762},
issn = {1476-5454},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy/psychology/therapy ; *Patient Satisfaction ; *Angiogenesis Inhibitors/therapeutic use ; Female ; Male ; Aged ; Quality of Health Care ; Surveys and Questionnaires ; Health Services Accessibility ; Aged, 80 and over ; Middle Aged ; Caregivers/psychology ; },
abstract = {BACKGROUND/OBJECTIVES: A positive patient experience is a key element of quality healthcare but data on the patient experience is rarely collected as part of routine care. This study analysed survey and discussion group comments from patients treated for neovascular AMD (nAMD) treatment to identify key elements of the patient experience.<br><br>SUBJECTS/METHODS: Free text comments from an online Macular Society member survey and quotes from subsequent, local, in-person patient discussion groups were reviewed. Thematic analysis was used to code the responses and to identify major themes.<br><br>RESULTS: Analysis include 167 free text comments from Macular Society members and quotes from 2 local discussion groups, with patients and their carers. Key themes, important for the patient experience, included: time and availability of appointments, accessibility and duration of clinic visits, the delivery and quality of care, communication and access to written information and confidence in the healthcare team.<br><br>CONCLUSIONS: Feedback from patients with nAMD and their carers identified a number of key themes that are associated with either a positive or negative patient experience. Construction of an appropriate patient-reported experience measure and collection of data, either locally or nationally, would help identify areas of the care pathway where improvements may be necessary. Improving the patient experience may encourage adherence to and persistence with treatment and the outcomes.},
}
@article {pmid40664371,
year = {2025},
author = {Grün, M and Rothaus, K and Lommatzsch, AP and Faatz, H},
title = {Early Outcome of Aflibercept 8 mg for Neovascular AMD in the Real-world Setting.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2655-8854},
pmid = {40664371},
issn = {1439-3999},
abstract = {PURPOSE: To investigate the early outcome of intravitreal aflibercept 8 mg in treating neovascular age-related macular degeneration (nAMD) of eyes that either received prior intravitreal anti-VEGF treatment or were treatment-naïve - under real-world conditions.<br><br>METHODS: This is a retrospective study of a total of 83 eyes with nAMD treated with aflibercept 8&#x2009;mg. 61 of these eyes completed an initial loading phase of 3 monthly intravitreal injections (IVI) and were included in further analyses. Outcome parameters included best-corrected visual acuity (BCVA, logMAR), presence of intraretinal (IRF) and subretinal fluid (SRF), extent of pigment epithelium detachment (PED height, &#xb5;m) and central subfield retinal thickness (CSRT, &#xb5;m) in spectral domain optical coherence tomography (SD-OCT). Patients were assessed at the beginning of aflibercept 8&#x2009;mg treatment and 4 weeks after completing the loading phase. The McNemar test was used to test for changes in distribution of eyes showing IRF and SRF, and the paired t test was performed to test for changes in BCVA, PED height and CSRT.<br><br>RESULTS: 51 eyes had been previously treated with intravitreal anti-VEGF, while 10 eyes were treatment-na&#xef;ve. Mean BCVA after completed loading phase was 0.49&#x2009;&#xb1;&#x2009;0.31&#x2009;logMAR and did not show changes to baseline BCVA, which was 0.49&#x2009;&#xb1;&#x2009;0.32&#x2009;logMAR (p&#x2009;=&#x2009;0.89). A significant reduction was observed in all disease activity parameters in SD-OCT. The proportion of eyes showing IRF and SRF decreased from 54.1% to 26.2% (p&#x2009;<&#x2009;0.001) and 65.6% to 24.6% (p&#x2009;<&#x2009;0.001), respectively. A reduction in PED height from 227.7&#x2009;&#xb1;&#x2009;114.6&#x2009;&#xb5;m at baseline to 191.9&#x2009;&#xb1;&#x2009;111.4&#x2009;&#xb5;m (p&#x2009;<&#x2009;0.001) and a decrease in CSRT from 375.2&#x2009;&#xb1;&#x2009;126.2&#x2009;&#xb5;m to 308.8&#x2009;&#xb1;&#x2009;93.7 (p&#x2009;<&#x2009;0.001) were recorded. Of all eyes (n&#x2009;=&#x2009;83) that had received at least one IVI aflibercept 8&#x2009;mg, 5 eyes (6.0%) developed symptomatic, non-infectious intraocular inflammation (IOI), which resolved completely with topical treatment.<br><br>CONCLUSION: Our results demonstrate good effectiveness of intravitreal aflibercept 8&#x2009;mg in the real-world setting, with significant reduction in disease activity parameters in SD-OCT after the loading phase with 3 monthly injections - while BCVA remained stable. While the PULSAR trial only included treatment-na&#xef;ve eyes, our study underlines the value of aflibercept 8&#x2009;mg, even for pre-treated eyes that responded insufficiently to previous anti-VEGF treatment. Further studies are needed to evaluate long-term outcome in real-world setting, in order to verify the extended IVI intervals shown in the PULSAR trial.},
}
@article {pmid40663469,
year = {2025},
author = {Palanker, D and Weiland, JD and Rosin, B and Sahel, JA},
title = {Restoration of Sight with Electronic Retinal Prostheses.},
journal = {Annual review of vision science},
volume = {11},
number = {1},
pages = {125-147},
doi = {10.1146/annurev-vision-110323-025244},
pmid = {40663469},
issn = {2374-4650},
mesh = {Humans ; *Visual Prosthesis ; *Blindness/rehabilitation/physiopathology ; *Retina ; *Electric Stimulation Therapy/methods ; Macular Degeneration/physiopathology ; Visual Acuity/physiology ; },
abstract = {Retinal prostheses aim at restoring sight to patients blinded by atrophy of photoreceptors using electrical stimulation of the inner retinal neurons. Bipolar cells can be targeted using subretinal implants, and their responses are then relayed to the central visual pathways via the retinal neural network, preserving many features of natural signal processing. Epiretinal implants stimulate the output retinal layer-ganglion cells-and encode visual information directly in spiking patterns.Several companies and academic groups have demonstrated that electrical stimulation of the degenerate retina can elicit visual percepts. However, most failed to consistently and safely achieve an acceptable level of performance. Recent clinical trials demonstrated that subretinal photovoltaic arrays in patients visually impaired by age-related macular degeneration can provide letter acuity matching their 100 μm pixel pitch, corresponding to 20/420 acuity. Electronic zoom enabled patients to read smaller fonts. This review describes the concepts, technologies, and clinical outcomes of current systems and provides an outlook into future developments.},
}
@article {pmid40662890,
year = {2025},
author = {Du, Y and Feng, L and Tang, J and Qin, X and Bai, B and Liang, L},
title = {C5a-Induced Autophagy Dysfunction Promotes Choroidal Neovascularization Through the ROS-Inflammatory Pathway.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {9},
pages = {44},
pmid = {40662890},
issn = {1552-5783},
mesh = {*Autophagy/drug effects/physiology ; *Choroidal Neovascularization/metabolism/pathology ; *Reactive Oxygen Species/metabolism ; Animals ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Humans ; Mice ; Disease Models, Animal ; Blotting, Western ; Cytokines/metabolism ; Enzyme-Linked Immunosorbent Assay ; Mitochondria/metabolism ; Macular Degeneration/metabolism ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness in aging populations. C5a is the primary component of drusen and exerts a pivotal role in AMD, facilitating its progression. In the present research, we explored how C5a exacerbates AMD pathogenesis and its interplay with autophagic pathways, mitochondrial reactive oxygen species (ROS), and proinflammatory cytokines.<br><br>METHODS: Human retinal pigment epithelial (ARPE-19) cells were exposed to recombinant C5a. Autophagy was modulated using rapamycin or 3-MA, and ROS dynamics were perturbed with DPI or rotenone. Autophagy markers (LC3-II, Beclin-1, p62/SQTSM1) were analyzed via Western blot. Mitochondrial ROS levels were quantified using MitoSOX Red, while cytokine secretion (VEGF, MCP-1, IL-6, and IL-8) was measured by ELISA. C57BL/6 mice were utilized to model choroidal neovascularization (CNV), a prevalent subtype of AMD, which was induced by laser photocoagulation.<br><br>RESULTS: C5a stimulation significantly increased LC3-II, Beclin-1, and p62/SQTSM1. The cytokine secretion (VEGF, MCP-1, IL-6, and IL-8), ROS, and the areas in laser-induced CNV were significantly enlarged after C5a treatment. Autophagy activator significantly downregulated the cytokine secretion (VEGF, MCP-1, IL-6, and IL-8), ROS, and the areas in laser-induced CNV. ROS inhibitors can markedly diminish IL-6, IL-8, MCP-1, and VEGF, as well as the progression of CNV.<br><br>CONCLUSIONS: Our results suggest that C5a induced the dysfunction of autophagy and increased the mitochondrial ROS, as well as the mitochondrial ROS-driven cytokine release that fuels CNV formation.},
}
@article {pmid40662679,
year = {2025},
author = {Chatterjee, S and Ghosh, S and Sin, Z and Babu, VS and Preval, LV and Davis, E and Tran, N and Bammidi, S and Gautam, P and Hose, S and Sergeev, Y and Flores-Bellver, M and Ritter, K and Jessen, HJ and Al Diri, I and Sinha, D and Guha, P},
title = {Age-Dependent Histone Deacetylase 3 Regulation by βA3/A1-Crystallin and Inositol Hexaphosphate in Retinal Pigmented Epithelial Cells Reveals a Novel Pathway in Age-Related Macular Degeneration.},
journal = {Aging cell},
volume = {24},
number = {9},
pages = {e70163},
pmid = {40662679},
issn = {1474-9726},
support = {R16 GM154726/GM/NIGMS NIH HHS/United States ; P20 GM121325/GM/NIGMS NIH HHS/United States ; P30 EY001765/EY/NEI NIH HHS/United States ; K99 EY033421/EY/NEI NIH HHS/United States ; NIH 5P20GM121325 COBRE/NH/NIH HHS/United States ; R01 EY032516/EY/NEI NIH HHS/United States ; R16GM154726/NH/NIH HHS/United States ; NIH 1R01EY032516-01A1/NH/NIH HHS/United States ; R01 EY031594/EY/NEI NIH HHS/United States ; EY001765/EY/NEI NIH HHS/United States ; NIH K99EY033421/NH/NIH HHS/United States ; NIH 1R01EY031594-01A1/NH/NIH HHS/United States ; },
mesh = {*Histone Deacetylases/metabolism/genetics ; Animals ; Humans ; *Macular Degeneration/metabolism/genetics/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; *Phytic Acid/metabolism ; *Aging/metabolism ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss affecting retinal pigment epithelial (RPE) cells, remains largely unexplained by current genome-wide association studies (GWAS) risk variants. Our research on Cryba1, encoding βA3/A1-crystallin protein, reveals its crucial role in RPE cell function via a novel epigenetic mechanism, also evident in human atrophic AMD samples. Loss of Cryba1 in mouse RPE cells triggers epigenetic changes by reducing histone deacetylase 3 (HDAC3) activity through two mechanisms. First, Cryba1 depletion reduces inositol polyphosphate multikinase (IPMK) expression, which potentially reduces inositol hexakisphosphate (InsP6) generation since IPMK's kinase activity is essential for producing InsP4 and InsP5 as precursors to InsP6. Since InsP4, InsP5, or InsP6 is crucial for HDAC3's interaction with the corepressor's DAD domains, reduced IPMK expression in Cryba1-depleted cells likely diminishes the HDAC3-DAD interaction, leading to a reduction in HDAC3's activity. Second, reduced βA3/A1 protein in Cryba1-deficient cells impairs HDAC3's interaction with casein kinase 2 (CK2), resulting in decreased HDAC3 phosphorylation. Collectively, this increases H3K27 acetylation at the RET promoter region, likely enhancing the transcription of RET, a receptor tyrosine kinase critical for cell survival. Although RET is transcriptionally increased, Cryba1 loss disrupts its protein maturation, causing immature RET protein accumulation. This triggers age-dependent endoplasmic reticulum (ER) stress, potentially contributing to the pathogenesis of AMD. Interestingly, although Cryba1 is not identified as an AMD-linked variant in current GWAS, its loss may be linked to AMD mechanisms. These findings underscore the potential of gene-agnostic and epigenetic therapeutic strategies for treating AMD.},
}
@article {pmid40661176,
year = {2025},
author = {Halev, A and Huang, D and Rezaei, S and Banks, S and McPherson, JD and Shankar, SP and Liu, X and Yiu, G},
title = {Genotype Prediction from Retinal Fundus Images Using Deep Learning in Eyes with Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {6},
pages = {100836},
pmid = {40661176},
issn = {2666-9145},
abstract = {PURPOSE: To employ deep learning models to predict high-risk genetic variants associated with age-related macular degeneration (AMD) from retinal fundus photographs of patients with this condition.<br><br>DESIGN: Deep learning algorithm development to classify single-nucleotide polymorphism in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes using retinal fundus images.<br><br>PARTICIPANTS: Thirty-one thousand two hundred seventy-one retinal color fundus photographs of 1754 participants from the Age-Related Eye Disease Study.<br><br>METHODS: We trained deep learning models including convolution neural networks and vision transformers (ViTs) to classify patients into high-risk (homozygous high-risk alleles) or low-risk (heterozygous or homozygous low-risk alleles) genotypes for CFH or ARMS2, then evaluated algorithm performance on an independent test set. The complexity of genotype predictions was compared with AMD severity or gender classification tasks using V-usable information. Attribution mapping was performed to identify fundus regions used to predict genotype from phenotype.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC), balanced accuracy, and average precision for predicting high-risk genotypes.<br><br>RESULTS: Our trained ViT models predicted high-risk genotypes in CFH and ARMS2 with an AUROC of 0.719 and 0.741 across all eyes, respectively. For genotype predictions for ARMS2, model performance is improved in eyes with advanced AMD (AUROC 0.867), choroidal neovascularization (AUROC 0.833), and geographic atrophy (AUROC 0.957). Genotype predictions from fundus images appear more difficult than AMD severity or gender classification tasks, although saliency mapping supports biological plausibility by demonstrating attention to the central macula for genotype predictions.<br><br>CONCLUSIONS: Deep learning can predict high-risk genotypes in CFH and ARMS2 from retinal fundus images of patients with AMD. Our findings provide proof of principle for inferring genotype from noninvasive eye imaging and reveal insights into genotype-phenotype relationships in AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40661080,
year = {2025},
author = {Li, X and Zhang, SQ and Wang, KR and Wu, SN and Wang, MY and Chen, CT and Dong, N},
title = {Chloroquine and hydroxychloroquine-related ocular adverse events in SLE treatment: a real-world disproportionality analysis based on FDA adverse event reporting system (FAERS).},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1498814},
pmid = {40661080},
issn = {1663-9812},
abstract = {OBJECTIVE: This study aimed to evaluate the risk of adverse events associated with chloroquine (CQ) and hydroxychloroquine (HCQ) in patients with systemic lupus erythematosus (SLE), using data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).<br><br>METHODS: Disproportionality analysis was conducted using the Reporting Odds Ratio (ROR) to detect potential safety signals. Sensitivity analyses were performed to validate these signals, and the time to onset for each Preferred Term (PT) was assessed.<br><br>RESULTS: Between 2004 and 2024, a total of 2,575 adverse event reports related to HCQ or CQ use in patients with SLE were identified in the FAERS database, of which 437 involved ocular adverse events. The most frequently reported ocular conditions were cataract, macular degeneration, and glaucoma. Disproportionality analysis demonstrated strong associations between HCQ/CQ use and retinal degeneration (ROR = 28.5, 95%CI: 19.94-40.74), cystoid macular oedema (ROR = 12.46, 95%CI: 8.01-19.37), and optic atrophy (ROR = 6.55, 95%CI: 3.51-12.19). Sensitivity analyses, conducted after excluding SLE cases, indicated that all but one event (vitreous floaters) remained statistically significant, suggesting that these risks are more likely attributable to HCQ/CQ exposure than to the underlying disease. The time-to-onset analysis showed that cataract had the shortest average onset time (125.5&#xa0;days), whereas retinal degeneration had the longest (937.5&#xa0;days).<br><br>CONCLUSION: The extensive clinical use of HCQ and CQ raises significant concerns regarding their ocular safety profile. This study provides real-world pharmacovigilance evidence supporting a substantial risk of ocular adverse events associated with HCQ/CQ use. Further mechanistic and prospective studies are warranted to elucidate the underlying pathophysiological pathways and to confirm these associations.},
}
@article {pmid40661075,
year = {2025},
author = {Liu, D and Chen, X and Cai, S},
title = {Inhibition of retinal neovascularization by Dendrobium polysaccharides: a review.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1584553},
pmid = {40661075},
issn = {1663-9812},
abstract = {Retinal neovascularization (RNV) is a critical pathological feature of vision-threatening ocular diseases, such as diabetic retinopathy, retinopathy of prematurity, and wet age-related macular degeneration, presenting a persistent therapeutic conundrum. Current clinical treatments primarily rely on anti-vascular endothelial growth factor (VEGF) drugs and laser therapies, which face limitations including drug resistance, high costs, and potential damage to normal tissues. This underscores the need to develop novel therapeutic targets and cost-effective pharmacological interventions with improved safety profiles. Recent investigations highlight Dendrobium polysaccharides (DP), the primary bioactive components of the traditional medicinal herb Dendrobium, as promising multi-target therapeutic candidates. Studies have shown that Dendrobium polysaccharides significantly inhibits pathological angiogenesis by regulating the VEGF signaling pathway, inhibiting inflammatory response and oxidative stress, protecting the extracellular matrix, and reversing intestinal microecological disorders. This review systematically summarizes the structural and functional properties of DP, explores their mechanism of action and experimental evidence in retinal neovascularization, and analyzes their potential as a new therapeutic strategy for retinal diseases. This review also highlights the main limitations of current research: the uncertain relationship between the structure and activity of DP, the differences between pre-clinical models and human diseases, and the potential for structural optimization and the development of delivery systems.},
}
@article {pmid40659110,
year = {2025},
author = {Kim, JY and Kim, S and Cho, J and Lee, JS and Lee, CS and Byeon, SH and Kim, SS and Lee, SW and Kim, YJ},
title = {Exudative AMD Risk Following Blue Light-Filtering IOL Implantation: A Population-Based Study According to Non-Exudative AMD Status.},
journal = {American journal of ophthalmology},
volume = {279},
number = {},
pages = {1-10},
doi = {10.1016/j.ajo.2025.07.007},
pmid = {40659110},
issn = {1879-1891},
mesh = {Humans ; Male ; Female ; Aged ; Incidence ; Republic of Korea/epidemiology ; *Lenses, Intraocular ; *Lens Implantation, Intraocular ; Middle Aged ; Risk Factors ; *Wet Macular Degeneration/epidemiology/etiology/diagnosis/prevention &amp; control ; Retrospective Studies ; Aged, 80 and over ; Follow-Up Studies ; Databases, Factual ; Visual Acuity ; Blue Light ; },
abstract = {PURPOSE: To evaluate whether blue light-filtering (BLF) intraocular lenses (IOLs) reduce the risk of exudative age-related macular degeneration (AMD).<br><br>DESIGN: A nationwide, population-based cohort study using data from the Korean National Health Insurance Sharing Service (NHISS) database.<br><br>PARTICIPANTS: Individuals who underwent cataract surgery and received the same type of IOL (BLF or clear) in both eyes within one year between January 2012 and December 2018.<br><br>METHODS: Participants were categorized into BLF IOL or clear IOL groups, and the risk of exudative AMD was compared between the 2 groups. The 10-year cumulative incidence of exudative AMD was estimated using Kaplan-Meier analysis. Cox proportional hazard models and the Fine-Gray model were applied to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), adjusting for age, sex, socioeconomic status, and systemic diseases. The same analysis was performed in the cohort matched by age, sex, and the calendar year of the index date.<br><br>MAIN OUTCOME MEASURES: 10-year cumulative incidence, incidence rate, and HR for exudative AMD.<br><br>RESULTS: A total of 21,741 individuals with BLF IOLs were compared to 56,357 individuals with clear IOLs. The mean follow-up duration was 7.0 &#xb1; 2.5 years in the BLF IOL group and 6.7 &#xb1; 2.5 years in the clear IOL group (P = .069). The 10-year cumulative incidence of exudative AMD was 1.8% (95% CI, 1.5%-2.0%) in the BLF IOL group and 1.7% (95% CI, 1.5%-1.8%) in the clear IOL group. The incidence rates per 100,000 person-years were 162.8 and 153.9 in the BLF IOL group and clear IOL groups, respectively, with no significant difference in the adjusted Cox model (aHR 1.12; 95% CI, 0.96-1.30; P = .149) and the Fine-Gray model (aHR 1.15; 95% CI, 0.97-1.36; P = .120). Subgroup analyses based on age, sex, and history of nonexudative AMD showed no protective effect of BLF IOLs, with comparable incidence rates across all subgroups. Similar results were observed in the matched cohort analysis.<br><br>CONCLUSIONS: BLF IOL implantation in cataract surgery does not reduce the risk of developing exudative AMD in the South Korean population, regardless of a history of nonexudative AMD.},
}
@article {pmid40658846,
year = {2025},
author = {Wang, Z and Anderson, DMG and Messinger, JD and Curcio, CA and Schey, KL},
title = {Glycolipids implicated as mediators of clinically visible retinal pigment epithelial migration in age-related macular degeneration.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {29},
pages = {e2503191122},
pmid = {40658846},
issn = {1091-6490},
support = {R01 EY029748//HHS | NIH | National Eye Institute (NEI)/ ; Catalyst Award//Research to Prevent Blindness (RPB)/ ; unrestricted funds//Research to Prevent Blindness (RPB)/ ; unrestricted funds//EyeSight Foundation of Alabama (ESFA)/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology ; Humans ; *Macular Degeneration/metabolism/pathology ; *Cell Movement ; *Glycolipids/metabolism ; Tomography, Optical Coherence ; Aged ; G(M3) Ganglioside/metabolism ; },
abstract = {The retinal pigment epithelium (RPE) is the metabolic gatekeeper to the photoreceptors, thus playing many essential roles in healthy vision. Under certain conditions, RPE cells may transdifferentiate and migrate from the RPE layer. Ectopic RPE cells are potential signal sources for hyperreflective foci, prominent clinically visible biomarkers in age-related macular degeneration, which causes central vision loss globally. Applying multiple imaging modalities including ex vivo optical coherence tomography, autofluorescence microscopy, and imaging mass spectrometry (IMS) to human retina tissue, we compared lipid profiles in ectopic and orthotopic RPE cells. Our results showed that ectopic RPE cells share some molecular signatures with normal RPE cells as revealed through autofluorescence imaging and IMS. In both orthotopic and ectopic RPE cells, IMS detected phosphatidylglycerol, PG 36:2, and several triacylglycerols containing long-chain fatty acids. GM3 gangliosides (40:1, 42:1, and 42:2) were also detected in ectopic RPE cells with differences in abundance in different populations of ectopic RPE cells. Lactosylceramide (LacCer 44:5) and glucosylceramide (GlcCer 44:5) were found exclusively in ectopic RPE cells. In contrast, ectopic RPE did not exhibit signals of phosphatidylinositols (PI) (PI32:0, PI32:1, PI34:1, and PI34:2) normally detected in RPE cells. Near-single-cell resolution IMS results suggest that RPE transdifferentiation, with loss of normal functions and gain of new functions like migration, may be linked to altered metabolism of glycosphingolipids and PIs.},
}
@article {pmid40658332,
year = {2025},
author = {Iida, T and Gomi, F and Yasukawa, T and Yamashiro, K and Honda, S and Maruko, I and Kataoka, K and , },
title = {Japanese clinical guidelines for neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {4},
pages = {639-660},
pmid = {40658332},
issn = {1613-2246},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Disease Management ; Fluorescein Angiography/methods ; Japan/epidemiology ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/diagnosis/therapy/epidemiology/drug therapy ; },
abstract = {Recent advances in imaging technology and increased options of pharmaceutical therapy require that guidelines on the diagnostic criteria and treatment of neovascular age-related macular degeneration (AMD) be updated at regular intervals. These guidelines aim to standardize the management of neovascular AMD based on the latest understanding of its pathophysiology, advancements in diagnostic imaging modalities, and treatment options. The key updates include: (1) a revision of terminology and stage classification, adopting the AMD classifications of atrophic and neovascular, and adding end-stage AMD to the existing early, intermediate, and late stages; (2) the inclusion of pachychoroid in addition to drusen in the initial pathophysiology and pathogenic background; (3) diagnostic criteria defined by the presence of macular neovascularization based on multimodal imaging, including optical coherence tomography (OCT) and OCT angiography; (4) assessment of disease activity based on OCT; and (5) treatment guidance, including prophylaxis and low vision care as well as loading and maintenance phases by use of anti-vascular endothelial growth factor therapy and adjunctive therapies. We hope that these guidelines will be useful for those working in clinical practice in Japan, in other Asian countries, and in countries outside Asia.},
}
@article {pmid40656874,
year = {2025},
author = {Hu, P and He, M and Cai, J and Lin, Z and Zheng, S and Zhuang, Z and Liu, J and Huang, L},
title = {Global burden of smoking-associated age-related macular degeneration: Spatiotemporal trends from 1990 to 2021 and projections to 2040.},
journal = {Tobacco induced diseases},
volume = {23},
number = {},
pages = {},
pmid = {40656874},
issn = {1617-9625},
abstract = {INTRODUCTION: Smoking is a major modifiable risk factor for age-related macular degeneration (AMD); however, the long-term trends and sociodemographic disparities in its global burden remain insufficiently characterized. This study aimed to assess the evolving burden of smoking-associated AMD from 1990 to 2021 and project its trajectory to 2040.<br><br>METHODS: Data from the Global Burden of Disease (GBD) 2021 database were used to extract smoking-associated AMD burden, measured by years lived with disability (YLDs) and age-standardized YLDs rate (ASYLDsR). Trends were stratified by sociodemographic index (SDI) and GBD super-regions, analyzed via estimated annual percentage change (EAPC), and projected using an autoregressive integrated moving average (ARIMA) model.<br><br>RESULTS: In 2021, the global burden of smoking-associated AMD reached 58858 YLDs (a 47.1% increase from 1990), with an ASYLDsR of 2.47 per 100000 population. The burden in males significantly exceeded the female burden (45442 vs 13417 YLDs in 2021), with a widening disparity. YLDs peaked in the age group of 65-69 years (12528 cases), while ASYLDsR increased with age. East Asia had the highest cases (23248 cases, 39.5% of the global total), whereas Central Asia exhibited rising ASYLDsR. ARIMA projections estimated global YLDs to rise to 72574 (95% CI: 61319-83828) by 2040, with ASYLDsR declining to 1.54 per 100000 (95% CI: 0.90-2.17).<br><br>CONCLUSIONS: The burden of smoking-associated AMD demonstrates marked demographic and geographical heterogeneity. Aging populations drive rising absolute case numbers, while disparities in tobacco control policies contribute to regional divergence in ASYLDsR.},
}
@article {pmid40656681,
year = {2025},
author = {Min, Y and Cuevas-Rios, G and Langmann, T and Neumann, H},
title = {Sialylation as a checkpoint for inflammatory and complement-related retinal diseases.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1623755},
pmid = {40656681},
issn = {1662-5102},
abstract = {Sialylation is a modification process involving the addition of sialic acid residues to the termini of glycoproteins and glycolipids in mammalian cells. Sialylation serves as a crucial checkpoint inhibitor of the complement and immune systems, particularly within the central nervous system (CNS), including the retina. Complement factor H (FH), complement factor properdin (FP), and sialic acid-binding immunoglobulin-like lectin (SIGLEC) receptors of retinal mononuclear phagocytes are key players in regulating the complement and innate immune systems in the retina by recognizing sialic acid (Sia) residues. Intact retinal sialylation prevents any long-lasting and excessive complement or immune activation in the retina. However, sialylated glycolipids are reduced in the CNS with aging, potentially contributing to chronic inflammatory processes in the retina. Particularly, genetically induced hyposialylation in mice leads to age-related, complement factor C3-mediated retinal inflammation and bipolar cell loss. Notably, most of the gene transcript pathways enriched in the mouse retina, following genetically induced hyposialylation, are also involved in age-related macular degeneration (AMD). Interestingly, intravitreal application of polysialic acid (polySia) controlled the innate immune responses in the mouse retina by blocking mononuclear phagocyte reactivity, inhibiting complement activation, and protecting against vascular damage in two different humanized SIGLEC-11 animal models. Accordingly, a polySia polymer conjugate has entered clinical phase II/III testing in patients with geographic atrophy secondary to AMD. Thus, hyposialylation or dysfunctional sialylation should be considered as an age-related contributor to inflammatory retinal diseases, such as AMD. Consequently, sialic acid-based biologics could provide novel therapies for complement-related retinal diseases.},
}
@article {pmid40656517,
year = {2025},
author = {Mansour, AM and Lima, LH and Battaglia Parodi, M and Casella, AMB and Cherfan, DG and Arevalo, JF},
title = {Outcomes of and Surgical Technique for Treatment With High-Dose Aflibercept.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251352890},
pmid = {40656517},
issn = {2474-1272},
abstract = {Purpose: To describe an alternate delivery of high-dose aflibercept using previous formulations (ie, prefilled syringe, vial, or compounded). Methods: A prospective pilot study was performed to analyze the short-term safety and visual gain (expressed in logMAR), including increase in intraocular pressure (IOP), resulting from a modified regimen consisting of 0.18 mL paracentesis followed by an intravitreal injection of 0.18 mL aflibercept (prefilled syringe), 0.20 mL aflibercept (vial), or 0.22 mL ziv-aflibercept (compounded). Results: The study comprised 32 eyes (16 naïve; 18 neovascular age-related macular degeneration; 8 retinal vein occlusion). Over a follow-up of 4.1 (± 3.2) months, a mean (± SD) of 1.7 (± 0.9) high-dose injections were administered. The baseline best spectacle-corrected vision was 1.35 ± 0.71 (Snellen VA) and improved to 0.68 ± 0.46 at 1 month (P < .001) and 0.57 ± 0.43 at the final follow-up (P < .001). An increase in IOP of 0.43 ± 4.26 mm Hg was seen 1 minute after injection (P = .58). In 2 eyes (6.3%), reflux as a tiny bleb was noted. Conclusions: When high-dose aflibercept is neither available nor affordable, a patient's readily accessible and cost-effective regimen of aflibercept will allow an exact delivery of high-dose aflibercept, combining minimal drug reflux, minimal immediate increase in IOP, and potential clinical efficacy in the short term.},
}
@article {pmid40655237,
year = {2025},
author = {O'Neill, Y and Arrigo, A and Stanga, PE},
title = {Addressing chronic visual hallucination by multimodal retinal imaging: a CBS case.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414251320032},
pmid = {40655237},
issn = {2515-8414},
abstract = {Charles Bonnet syndrome (CBS) is characterised by visual hallucinations in individuals with significant visual impairment. This literature review and case report focus on the unique presentation of CBS in an 82-year-old woman with age-related macular degeneration, who experienced visual hallucinations for over 10 years. The aim is to raise awareness of CBS among healthcare professionals and the public, addressing the diagnostic challenges that contribute to its underdiagnosis and mismanagement. A literature review was conducted to assess the prevalence and diagnosis of CBS. Databases including Google Scholar and PubMed were searched using the terms 'Charles Bonnet Syndrome', 'Case report' and 'Diagnosis'. The patient reported a range of visual hallucinations, from simple geometric shapes to highly detailed figures. A diagnosis of CBS was made based on her visual impairment and the nature of the hallucinations. No treatment was required, and the patient was reassured that the hallucinations were benign and unrelated to any psychiatric or neurological disorder. This case highlights the diagnostic challenges associated with CBS, which is often misdiagnosed or overlooked due to its rarity and the hesitancy of patients to disclose their symptoms. The long period of unreported hallucinations in this case emphasises the need for greater awareness among healthcare providers, enabling earlier recognition of CBS and differentiation from other conditions. The wide range of hallucination types seen in CBS adds to the complexity of the syndrome. The key takeaway is that increased awareness and recognition of CBS are essential for proper diagnosis, reducing patient anxiety and avoiding unnecessary treatments. This case contributes to the existing literature by illustrating the broad spectrum of CBS presentations and advocating for enhanced education on the condition.},
}
@article {pmid40653679,
year = {2025},
author = {Liu, J and Yi, C and Qi, J and Cui, X and Yuan, X and Deng, W and Chen, M and Xu, H},
title = {Senescence Alters Antimicrobial Peptide Expression and Induces Amyloid-β Production in Retinal Pigment Epithelial Cells.},
journal = {Aging cell},
volume = {24},
number = {9},
pages = {e70161},
pmid = {40653679},
issn = {1474-9726},
support = {2023JJ70047//Hunan Provincial Natural Science Foundation of China/ ; 2025JJ90270//Hunan Provincial Natural Science Foundation of China/ ; AM2201D02//Science Research Foundation of Aier Eye Hospital Group/ ; AMF2401D05//Science Research Foundation of Aier Eye Hospital Group/ ; AEI202304JC01//Science Research Foundation of Aier Eye Institute/ ; KY24002//Philanthropy Foundation of Xiangjiang/ ; KY24008//Philanthropy Foundation of Xiangjiang/ ; AIM2301D02//Clinical Research Foundation of Aier Eye Hospital Group/ ; MR/W004682/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Amyloid beta-Peptides/metabolism/biosynthesis ; *Retinal Pigment Epithelium/metabolism/cytology ; *Cellular Senescence ; *Antimicrobial Peptides/metabolism/genetics ; Amyloid Precursor Protein Secretases/metabolism ; *Epithelial Cells/metabolism ; },
abstract = {Age-related retinal degeneration, such as diabetic retinopathy and age-related macular degeneration, are major causes of blindness in modern society. Recent studies suggest that dysbiosis and intraocular translocation of bacteria from the blood circulation are critically involved in retinal degeneration. We hypothesise that the blood-retinal barrier (BRB) cells can protect the neuroretina from blood-borne pathogens by producing antimicrobial peptides (AMPs). The antimicrobial activity may decline during ageing, putting the retina at risk of low-degree chronic inflammation and degeneration. Here, we found that the retinal pigment epithelial (RPE) cells, which form the outer BRB, express a variety of AMPs/AMP precursors, including APP, RARRES2, FAM3A, HAMP, CAMP, GNLY, and PI3. Senescent RPE cells expressed lower levels of APP and RARRES2 mRNA, accompanied by increased intracellular retention of E. coli in a bactericidal assay. Silencing APP, not RARRES2, with shRNA reduced the antibacterial activity of RPE cells. Senescent RPE cells had lower levels of α-secretase and higher levels of β-secretase (BACE1) and γ-secretase (PS1), accompanied by reduced soluble APPα and increased amyloid beta (Aβ) production, particularly the Aβ42 isoform. Eyes from aged donors showed a higher Aβ accumulation within RPE cells. Our results suggest that while RPE cells possess antimicrobial activity, this ability declines with age and is impaired in senescent cells. The impaired antimicrobial activity and augmented Aβ deposition in senescent RPE cells may contribute to age-related retinal para-inflammation and neurodegeneration.},
}
@article {pmid40653498,
year = {2025},
author = {Yan, C and Yi, Q and Ge, L and Huang, Y and Yang, C and Lin, B and Jiang, D and Zhou, M},
title = {Metabolomics analysis uncovers metabolic changes and remodeling of anti-VEGF therapy on macular edema.},
journal = {Eye and vision (London, England)},
volume = {12},
number = {1},
pages = {28},
pmid = {40653498},
issn = {2326-0254},
support = {82000909//National Natural Science Foundation of China/ ; 62372331//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Anti-angiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) is currently the first-line treatment for macular edema (ME), but the specific metabolic changes in the aqueous humor (AH) after intravitreal anti-VEGF injections remain poorly understood.<br><br>METHODS: A total of 120 AH samples from 60 ME patients before and after anti-VEGF treatment were collected from the ophthalmology clinic and ward of the Eye Hospital of Wenzhou Medical University. Non-targeted metabolomics analysis of the AH samples was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify metabolite differences before and after anti-VEGF treatment in patients with different ME etiologies.<br><br>RESULTS: Distinct metabolomic profiles were observed between pre- and post-treatment samples. A total of 145 significantly altered metabolites were identified after anti-VEGF treatment, with 84 upregulated metabolites related to carbohydrate and amino acid metabolism, and 61 downregulated metabolites involved in amino acid metabolism. Both common and etiology-specific metabolic alterations were observed. In age-related macular degeneration (AMD)-ME, treatment-induced metabolic changes mainly involved amino acid metabolism, whereas in branch retinal vein occlusion (BRVO)-ME, lipid metabolism was primarily affected. Diabetic macular edema (DME) patients showed more complex metabolic alterations, involving amino acid, lipid and carbohydrate metabolism.<br><br>CONCLUSIONS: Intravitreal anti-VEGF injections significantly alter AH metabolites in ME patients. These findings provide insight into underlying metabolic processes in ME pathogenesis and treatment efficacy.},
}
@article {pmid40653260,
year = {2025},
author = {Lak, S and Kanavi, MR and Bayat, K and Ahmadieh, H and Soheili, ZS and Suri, F},
title = {Differential expression profiles of MAPT (TAU) gene isoforms in dry age-related macular degeneration.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110517},
doi = {10.1016/j.exer.2025.110517},
pmid = {40653260},
issn = {1096-0007},
mesh = {Humans ; *tau Proteins/genetics/biosynthesis ; Middle Aged ; Male ; Female ; Aged ; Protein Isoforms/genetics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger/genetics ; *Geographic Atrophy/genetics/metabolism ; *Gene Expression Regulation/physiology ; Adult ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is a neurodegenerative retinal disorder that typically emerges later in life and is the primary cause of central visual loss. The microtubule-associated protein Tau (MAPT) gene produces six significant splice variants in neural cells, which are differentiated by the exclusion or inclusion of exon 10, resulting in expression of 3R and 4R isoforms. Changes in Tau expression and the ratio of 4R-3R isoforms have been observed in various neurodegenerative diseases; however, the expression of Tau mRNA in AMD remains unexplored. This study represents the first investigation into the expression of MAPT transcript variants in patients with dry AMD. Human donor eyes were sourced from the Iranian Eye Bank and divided into three categories: Dry-AMD (aged ≥50 years, n = 13), Elderly-Normal (aged ≥50 years, n = 13), and Young-Normal (aged ≤40 years, n = 10). Retinal RNA was isolated, and quantitative real-time PCR (qRT-PCR) was employed to evaluate total Tau, as well as the 3R, and 4R transcript variants using specific primers. Dry-AMD samples showed a mixture of 3R and 4R isoforms, with no significant difference in total Tau levels when compared to both control groups. However, the 4R/3R ratio was significantly higher in Dry-AMD samples compared to both control groups, while no significant difference was observed between elderly and young controls. These findings indicate that changes in the 4R/3R Tau ratio may play a role in the progression of Dry-AMD, potentially triggering pathways that promote disease advancement. Further research is necessary to explore these results across various stages of the disease.},
}
@article {pmid40649951,
year = {2025},
author = {Jiang, F and Ma, J and Lei, C and Zhang, Y and Zhang, M},
title = {Age-Related Macular Degeneration: Cellular and Molecular Signaling Mechanisms.},
journal = {International journal of molecular sciences},
volume = {26},
number = {13},
pages = {},
pmid = {40649951},
issn = {1422-0067},
support = {2024YFFK0303//Sichuan Provincial Science and Technology Support Project/ ; 82301232//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Macular Degeneration/metabolism/pathology/etiology ; *Signal Transduction ; Retinal Pigment Epithelium/metabolism/pathology ; Oxidative Stress ; Animals ; Choroidal Neovascularization/metabolism/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a progressive retinal disorder and a leading cause of irreversible blindness among elderly individuals, impacting millions of people globally. This review synthesizes the current understanding of the cellular and molecular signaling mechanisms driving AMD, with a focus on the distinct pathophysiological features of dry and wet AMD subtypes. Key mechanisms include oxidative stress, inflammation, lipid metabolism dysregulation, and immune dysregulation, all of which converge on the retinal pigment epithelium (RPE) as a central player in disease initiation and progression. In dry AMD, oxidative damage, mitochondrial dysfunction, and lipofuscin accumulation impair RPE function, contributing to drusen formation and geographic atrophy. In wet AMD, vascular endothelial growth factor-mediated angiogenesis, coupled with inflammation and endothelial metabolic reprogramming, drives choroidal neovascularization. This article integrates findings from multiomics approaches and highlights the potential of artificial intelligence in elucidating AMD pathogenesis and advancing personalized therapies. Future research directions emphasize targeting these molecular pathways to develop innovative treatments, offering hope for improved management of this debilitating condition.},
}
@article {pmid40649894,
year = {2025},
author = {Camelo, S},
title = {Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy.},
journal = {International journal of molecular sciences},
volume = {26},
number = {13},
pages = {},
pmid = {40649894},
issn = {1422-0067},
support = {P170919//Programme Hospitaller de Recherche Clinique (PHRC) - 2017 (French Ministry of Health)./ ; },
mesh = {Humans ; *NF-E2-Related Factor 2/metabolism/antagonists &amp; inhibitors ; *Dimethyl Fumarate/therapeutic use/pharmacology ; *Drug Repositioning ; *Geographic Atrophy/drug therapy/metabolism/pathology ; Animals ; Oxidative Stress/drug effects ; Macular Degeneration/drug therapy ; },
abstract = {Recently, marketing authorizations were granted by the Federal Drug Administration (FDA) for pegcetacoplan and avacincaptad pegol, which inhibit C3 and C5 complement components, respectively. These two drugs were demonstrated to slow down the growth of atrophic areas in the retina. These authorizations represent a huge breakthrough for patients suffering from geographic atrophy (GA), the late stage of the dry form of Age-related Macular Degeneration (AMD). Until then, no treatment was available to treat this blinding disease. However, these two new compounds inhibiting the complement system are still not available for patients outside of the United States, and they are not devoid of drawbacks, including a poor effect on vision improvement, an increased risk of occurrence of the neovascular form of AMD and the burden of patients receiving recurrent intravitreal injections. Thus, the important medical need posed by GA remains incompletely answered, and new therapeutic options with alternative modes of action are still required. Oxidative stress and inflammation are two major potential targets to limit the progression of atrophic retinal lesions. Dimethyl fumarate, dimethyl itaconate and other activators of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) display antioxidants and immunomodulatory properties that have shown evidence of efficacy in in vitro and in vivo models of dry AMD. Tecfidera[®], whose active principle is dimethyl fumarate, is already commercialized for the treatment of autoimmune diseases such as multiple sclerosis and psoriasis. The aim of this review is to present the rationale and the design of the clinical trial we initiated to test the effectiveness and safety of repurposing Tecfidera[®], which could represent a new therapeutic alternative in patients with the dry form of AMD.},
}
@article {pmid40648575,
year = {2025},
author = {Confalonieri, F and Hertzberg, SNW and Dziedzic, KA and Lumi, X and Lytvynchuk, L and Znaor, L and Petrovski, G and Petrovski, B&#xc9;},
title = {Cost-Effectiveness of Alternative Treatment Strategies of Subretinal Macular Hemorrhage.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {13},
pages = {},
pmid = {40648575},
issn = {2227-9032},
abstract = {Purpose: To evaluate the cost-effectiveness of alternative treatment strategies for subretinal macular hemorrhage (SRMH), a condition often associated with neovascular age-related macular degeneration (AMD) and other retinal vascular disorders, leading to severe visual impairment. Methods: A retrospective cross-sectional study conducted at Oslo University Hospital assessed the cost and utility of various SRMH treatment modalities. These included intravitreal anti-VEGF monotherapy, intravitreal tissue plasminogen activator (tPA) with gas displacement (alone and in combination with anti-VEGF), and pars plana vitrectomy (PPV) with subretinal tPA and gas displacement (with and without anti-VEGF). Costs were analyzed from a healthcare perspective, encompassing direct and indirect costs. Effectiveness was measured using median best-corrected visual acuity (BCVA) improvements. Sensitivity analyses were performed to account for complications and variations in follow-up. Results: Anti-VEGF monotherapy was the most cost-effective treatment, with the lowest cost per unit of BCVA improvement (NOK 44,717) in outpatient settings. Intravitreal tPA with gas displacement emerged as a cost-effective alternative but exhibited higher costs when combined with anti-VEGF or performed as an inpatient procedure. PPV with subretinal tPA and gas displacement, with or without anti-VEGF, was the least cost-effective modality, particularly in inpatient settings. Sensitivity analyses indicated that anti-VEGF therapy remained cost-effective even with increased follow-up requirements and complications, while tPA-based therapies required significant BCVA improvements to match anti-VEGF's cost-utility. Conclusions: Outpatient intravitreal anti-VEGF monotherapy followed by tPA with gas displacement are the most cost-effective strategies for SRMH management. Subretinal tPA-based treatments are associated with higher costs and limited economic viability, highlighting the importance of tailored treatment selection. These findings support strategic resource allocation in managing SRMH while optimizing patient outcomes.},
}
@article {pmid40647687,
year = {2025},
author = {Ranetti, AE and Stanca, HT and Munteanu, M and Bievel Radulescu, R and Stanca, S},
title = {Blue Light and Green Light Fundus Autofluorescence, Complementary to Optical Coherence Tomography, in Age-Related Macular Degeneration Evaluation.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {13},
pages = {},
pmid = {40647687},
issn = {2075-4418},
abstract = {Background: Age-related macular degeneration (AMD) is one of the leading causes of permanent vision loss in the elderly, particularly in higher-income countries. Fundus autofluorescence (FAF) imaging is a widely used, non-invasive technique that complements structural imaging in the assessment of retinal pigment epithelium (RPE) integrity. While optical coherence tomography (OCT) remains the gold standard for retinal imaging due to its high-resolution cross-sectional visualization, FAF offers unique metabolic insights. Among the FAF modalities, blue light FAF (B-FAF) is more commonly employed, whereas green light FAF (G-FAF) provides subtly different image characteristics, particularly improved visualization and contrast in the central macula. Despite identical acquisition times and nearly indistinguishable workflows, G-FAF is notably underutilized in clinical practice. Objectives: This narrative review critically compares green and blue FAF in terms of their diagnostic utility relative to OCT, with a focus on lesion detectability, macular pigment interference, and clinical decision-making in retinal disorders. Methods: A comprehensive literature search was performed using the PubMed database for studies published prior to February 2025. The search utilized the keywords fundus autofluorescence and age-related macular degeneration. The primary focus was on short-wavelength FAF and its clinical utility in AMD, considering three aspects: diagnosis, follow-up, and prognosis. The OCT findings served as the reference standard for anatomical correlation and diagnostic accuracy. Results: Both FAF modalities correlated well with OCT in detecting RPE abnormalities. G-FAF demonstrated improved visibility of central lesions due to reduced masking by macular pigment and enhanced contrast in the macula. However, clinical preference remained skewed toward B-FAF, driven more by tradition and device default settings than by evidence-based superiority. G-FAF's diagnostic potential remains underrecognized despite its comparable practicality and subtle imaging advantages specifically for AMD patients. AMD stages were accurately characterized, and relevant images were used to highlight the significance of G-FAF and B-FAF in the examination of AMD patients. Conclusions: While OCT remains the gold standard, FAF provides complementary information that can guide management strategy. Since G-FAF is functionally equivalent in acquisition, it offers slight advantages. Broader awareness and more frequent integration of G-FAF that could optimize multimodal imaging strategies, particularly in the intermediate stage, should be developed.},
}
@article {pmid40646244,
year = {2025},
author = {Negiloni, K and Baskaran, P and Rao, DP and Maitray, A and Savoy, FM and Suresh, S and Mahalingam, M and Vighnesh, MJ and Rajendran, A},
title = {Advancing AMD screening with an offline, AI-powered smartphone-based fundus camera: A prospective, real-world clinical validation.},
journal = {Eye (London, England)},
volume = {39},
number = {13},
pages = {2548-2554},
pmid = {40646244},
issn = {1476-5454},
mesh = {Humans ; Prospective Studies ; *Smartphone/instrumentation ; Middle Aged ; Female ; Male ; Aged ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnosis ; Algorithms ; Fundus Oculi ; *Photography/instrumentation ; *Artificial Intelligence ; Sensitivity and Specificity ; Reproducibility of Results ; *Diagnostic Techniques, Ophthalmological/instrumentation ; },
abstract = {OBJECTIVES: This study evaluated a novel offline, AI-driven age-related macular degeneration (AMD) screening algorithm against fundus image-only grading and the standard of care (combined Spectral Domain-Optical Coherence Tomography (SD-OCT) and fundus image grading).<br><br>METHODS: Conducted prospectively at a South Asian tertiary eye hospital, this study utilized a validated smartphone-based non-mydriatic fundus camera to capture macula-centred images. The Medios AI's ability to detect referable AMD was compared to a reference standard image grading, using fundus images from the Zeiss Clarus 700 table-top camera and SD-OCT line scan across fovea. Three retina specialists provided blinded AMD diagnoses based on: (1) Zeiss Clarus 700 fundus images alone, and (2) combined SD-OCT and fundus images (standard of care). Referable AMD was defined as intermediate or advanced AMD.<br><br>RESULTS: Among 984 eyes from 492 patients (mean age 61.8&#x2009;&#xb1;&#x2009;9.9 years), 52% had referable AMD. Inter-grader agreement was strong, with Cohen's Kappa scores of 0.81-0.84. The Medios AI's sensitivity and specificity for detecting referable AMD against fundus-only grading (n&#x2009;=&#x2009;492) were 88.48% (95% CI: 84.04-92.03%) and 87% (95% CI: 81.86-91.11%), respectively. Against combined grading (n&#x2009;=&#x2009;489), AI sensitivity was 90.62% (95% CI: 86.37-93.90%), and specificity was 85.41% (95% CI: 80.21-89.68%). False negatives were primarily intermediate AMD (71%), while 59% of false positives were early AMD.<br><br>CONCLUSION: The novel, automated, offline AMD AI integrated on a smartphone fundus camera demonstrated robust performance in identifying referable forms of AMD, supporting its potential as an affordable and accessible screening solution.},
}
@article {pmid40643526,
year = {2025},
author = {Dörschmann, P and von der Weppen, S and Koyama, E and Roider, J and Klettner, A},
title = {Porcine Single-Eye Retinal Pigment Epithelium Cell Culture for Barrier and Polarity Studies.},
journal = {Cells},
volume = {14},
number = {13},
pages = {},
pmid = {40643526},
issn = {2073-4409},
support = {03LW0148//Bundesministerium f&#xfc;r Bildung und Forschung/ ; },
mesh = {*Retinal Pigment Epithelium/cytology/metabolism ; Animals ; Swine ; *Cell Polarity ; Cells, Cultured ; *Cell Culture Techniques/methods ; Electric Impedance ; Bestrophins/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the main cause of blindness in Western nations. AMD models addressing specific pathological pathways are desired. Through this study, a best-practice protocol for polarized porcine single-eye retinal pigment epithelium (RPE) preparation for AMD-relevant models of RPE barrier and polarity is established. Single-eye porcine primary RPE cells (from one eye for one well) were prepared in 12-well plates including Transwell inserts. Different coatings (laminin (Lam), Poly-ᴅ-Lysine (PDL), fibronectin (Fn) and collagens) and varying serum contents (1%, 5% and 10%) were investigated to determine optimal culture parameters for this model. Success rates of cultures, cell number (trypan-blue exclusion assay), morphology/morphometry (light and fluorescence microscopy), protein secretion/expression (ELISA, Western blot), gene expression (qPCR), transepithelial electric resistance (TEER) and polar location of bestrophin 1 (BEST1) by cryosectioning (IHC-Fr) were assessed. Cells seeded on Lam exhibited the highest level of epithelial cells and confluence properties. Fn resulted in the highest cell number growth. Lam and Fn exhibited the highest culture success rates. TEER values and vascular endothelial growth factor secretion were highest when Lam was used. For the first time, polar (Transwell) porcine single-eye RPE morphometry parameters were determined. RPE on Lam showed bigger cells with a higher variety of cell shapes. CIV displayed the lowest claudin 19 expression. The highest basolateral expression of BEST1 was achieved with Lam coating. The higher the serum, the better the cell number increase and confluence success. A reduction in serum on Lam showed positive results for RPE morphology, while morphometry remained stable. A five percent serum on Lam showed the highest culture success rate and best barrier properties. RPE65 expression was reduced by using 10% serum. Altogether, the most suitable coating of Transwell inserts was Lam, and a reduction in serum to 5% is recommended, as well as a cultivation time of 28 days. A protocol for the use of polar porcine single-eye cultures with validated parameters was established and is provided herein.},
}
@article {pmid40640441,
year = {2025},
author = {Balogh, B and Zille, M and Szarka, G and Péntek, L and Futácsi, A and Völgyi, B and Kovács-Öller, T},
title = {Local microglial activation induced and labeled in the retina in a novel subretinal hemorrhage mouse model.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {24804},
pmid = {40640441},
issn = {2045-2322},
mesh = {Animals ; *Microglia/metabolism/pathology ; *Retinal Hemorrhage/pathology/metabolism ; Mice ; Disease Models, Animal ; *Retina/pathology/metabolism ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/pathology/metabolism ; Cholera Toxin/metabolism ; },
abstract = {Subretinal hemorrhage (SRH) is caused by the accumulation of blood between the neurosensory retina and the retinal pigment epithelium or between the retinal pigment epithelium and the choroid. SRH often arises from age-related macular degeneration, traumas, and may occur spontaneously caused by other diseases like hypertension and diabetes. Here, we developed a novel technique - co-injection of blood and a dye-coupled tracer protein, Cholera toxin subunit B (CtB) - to better localize and understand the disease and how it can cause microglial activation, inflammation, and partial vision loss. Our results show that microglia are activated in the inner retinal layers in zones adjacent to blood injection. In contrast, the non-affected zone of the injected eye showed no microglial activation. For the first time, we used phosphate-buffered saline (PBS) injections as a control to assess the specific effects of injected blood. The results demonstrated that blood induced a markedly stronger activation response in the surrounding tissue, whereas PBS elicited a comparatively milder effect. PBS did cause microglial activation, but it was largely confined to the injection site and adjacent regions, and to a lesser extent than that observed with blood. We also observed microglial activation in the inner retina, along with the emergence of microglia and macrophages in the retinal pigment epithelium. Using advanced imaging techniques, we were able to better localize the affected area which comprises not only the immediate retinal area over the blood clot but the neighboring regions as well. These findings will provide the basis for novel therapeutic interventions targeting neuroinflammation in the retina after subretinal hemorrhage and other diseases affecting the eye.},
}
@article {pmid40640104,
year = {2025},
author = {Wood, AJ and Livingstone, I and Westcott, M and Furniss, D and Wiberg, A},
title = {A review of the role of EFEMP1 in ophthalmic disease.},
journal = {Ophthalmic genetics},
volume = {46},
number = {6},
pages = {523-531},
doi = {10.1080/13816810.2025.2524511},
pmid = {40640104},
issn = {1744-5094},
mesh = {Humans ; *Extracellular Matrix Proteins/genetics ; Genome-Wide Association Study ; Mutation ; *Eye Diseases/genetics ; },
abstract = {EGF-containing fibulin extracellular matrix protein 1 (EFEMP1), or fibulin-3, is an extracellular matrix glycoprotein encoded by the EFEMP1 gene. The role of EFEMP1 in the human eye is incompletely understood, but there are well-reported associations between mutations in the gene and a variety of ophthalmic diseases, such as myopia, juvenile open-angle glaucoma (JOAG), primary open-angle glaucoma (POAG) and familial drusen formation in Malattia Leventinese (ML)/Doyne honeycomb retinal dystrophy (DHRD). Variants which interact with EFEMP1 have also been identified in genome-wide association studies (GWAS) for age-related macular degeneration (AMD). Many of these conditions form a large component of ophthalmology case-load and have incompletely characterized pathogenesis. In this review, we will describe the role of EFEMP1 in ophthalmic disease. We discuss the role of EFEMP1 in Mendelian eye disease, its polygenic contributions to common ophthalmic conditions, and the potential to target EFEMP1 for therapeutic purposes.},
}
@article {pmid40639430,
year = {2025},
author = {Hollaus, M and Baratsits, M and Steiner, I and Weigert, G and Pawloff, M and Mylonas, G and Schmidt-Erfurth, U and Sacu, S},
title = {Long-term effects of drusenoid pigment epithelial detachment on the retina and the choroid.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2025.06.010},
pmid = {40639430},
issn = {1715-3360},
abstract = {OBJECTIVE: To analyze the long-term effects of drusenoid pigment epithelial detachment (DPED) on the overlying inner and outer retinal layers and the underlying choroid.<br><br>METHODS: Forty-two eyes from 33 patients with DPED due to intermediate age-related macular degeneration were included in this prospective observational cohort study, which was conducted from December 2017 until July 2023. Patients underwent spectral-domain optical coherence tomography every 6 months. Evaluated parameters included maximum DPED height (=DPED apex) and location of the DPED apex at baseline; furthermore, DPED height, retinal thickness (RT), visibility of retinal layers, presence of hyperreflective foci (HRF), choroidal thickness (CT), and best-corrected visual acuity (BCVA) at baseline and each follow-up visit, as well as development of macular neovascularization or geographic atrophy.<br><br>RESULTS: DPED height, RT, and CT did not change significantly during the observation period (all p values > 0.05). DPED height and RT correlated significantly regardless of visit (estimate&#x202f;=&#x202f;-0.36, 95% CI&#x202f;=&#x202f;-0.4 to -0.32; p < 0.0001), DPED height, and CT did not (p > 0.05). Outer retina (estimate&#x202f;=&#x202f;-2.19, 95% Cl&#x202f;=&#x202f;-2.74 to -1.63; p < 0.0001), location in the central millimeter (estimate&#x202f;=&#x202f;-0.79, 95% Cl&#x202f;=&#x202f;-1.31 to -0.27; p&#x202f;=&#x202f;0.004), and the presence of HRF (estimate&#x202f;=&#x202f;-0.65, 95% Cl&#x202f;=&#x202f;-1.05 to -0.24; p&#x202f;=&#x202f;0.003) were significantly associated with retinal layer visibility regardless of visit, while DPED height was not (p > 0.05). BCVA was not significantly associated with DPED height, RT, CT, or the number of visible outer and inner retinal layers regardless of visit (all p values > 0.05).<br><br>CONCLUSIONS: Our results indicate that increasing DPED height may significantly reduce the thickness of the overlying retina but not of the underlying choroid. Fewer outer retinal layers were visible compared to the inner retina at the DPED apex. Location in the central millimeter of the macula and presence of HRF also reduced the number of visible retinal layers. Impairment of the retinal morphology, which seems to be more pronounced in the outer than the inner retina, need not be accompanied by functional impairment and can recover in case of DPED regression.},
}
@article {pmid40637952,
year = {2025},
author = {Matsumoto, H and Hoshino, J and Numaga, S and Asatori, Y and Akiyama, H},
title = {Loading phase outcomes of intravitreal aflibercept 8 mg for treatment-naïve neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {6},
pages = {911-917},
pmid = {40637952},
issn = {1613-2246},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Follow-Up Studies ; Aged, 80 and over ; Fundus Oculi ; Angiogenesis Inhibitors/administration &amp; dosage ; Dose-Response Relationship, Drug ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Choroid/pathology ; Macula Lutea/pathology ; },
abstract = {PURPOSE: To investigate the efficacy and safety of loading phase treatment with 3 monthly intravitreal injections of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively analyzed 83 consecutive eyes of 80 patients with treatment-na&#xef;ve nAMD who received 3 monthly injections of aflibercept 8 mg as a loading phase treatment. Best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), and dry macula achievement were all assessed every 4 weeks. Moreover, polypoidal lesion regression was evaluated after the loading phase.<br><br>RESULTS: Seventy eyes (84.3%) of 67 patients completed the 3 monthly injections of aflibercept 8 mg. In these cases, BCVA was 0.33&#xb1;0.45 at baseline and showed significant improvement to 0.22&#xb1;0.38 at week 12 (P<0.01). Foveal thickness was 313&#xb1;135&#xb5;m at baseline, decreasing significantly to 171&#xb1;76&#xb5;m at week 12 (P<0.01). CCT was 193&#xb1;98&#xb5;m at baseline, decreasing significantly to 160&#xb1;85&#xb5;m at week 12 (P<0.01). Dry macula had been achieved in 58 (82.9%) of 70 eyes at week 12. Indocyanine green angiography after the loading phase revealed complete polypoidal lesion regression in 16 of 22 eyes (72.7%) with polypoidal lesions. Among the 13 eyes (15.7%) not completing the loading phase treatment, 9 (10.8%) developed non-infectious intraocular inflammation (IOI) associated with retinal vasculitis and aflibercept 8 mg administration was thus discontinued.<br><br>CONCLUSIONS: Loading phase treatment with intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, careful monitoring is required due to the potential development of IOI associated with retinal vasculitis.},
}
@article {pmid40636510,
year = {2025},
author = {Chen, C and Guo, D and Meng, J and Qi, J and Zhang, K and He, W and Tham, YC and Zhu, X},
title = {Grip Strength and Age-Related Ocular Diseases: Insights from Observational, Mendelian Randomization, and Mediation Analyses.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100831},
pmid = {40636510},
issn = {2666-9145},
abstract = {OBJECTIVE: We aimed to examine the cross sectional and causal associations of grip strength with cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) and probe the underlying mechanisms by evaluating the mediating role of metabolomic alterations.<br><br>DESIGN: Cross sectional study.<br><br>SUBJECTS: A total of 307 796 UK Biobank participants with grip strength and covariates data available.<br><br>METHODS: Logistic regression models were used to evaluate the associations between grip strength and age-related ocular diseases. Two-sample Mendelian randomization analyses were conducted to assess the causality. Metabolic biomarkers from plasma samples were measured through nuclear magnetic resonance (n = 152 376), and principal component (PC) analysis was implemented to identify metabolic patterns (PC1-PC8). The mediation effects of both metabolic biomarkers and metabolic patterns were examined.<br><br>MAIN OUTCOME MEASURES: The prevalence of age-related ocular diseases.<br><br>RESULTS: Compared with the highest tertile of grip strength, the lowest tertile had a higher prevalence of cataract (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.24-1.39), glaucoma (OR, 1.23; 95% CI, 1.13-1.33), and DR (OR, 2.80; 95% CI, 2.32-3.38). Genetic-associated elevated grip strength of at least 1 hand was associated with a lower risk of developing cataracts, DR, and AMD. Mediation analyses showed metabolic patterns, characterized by altered lipids and omega-3 polyunsaturated fatty acids (PUFAs) decrement (i.e., PC2 and PC8), significantly mediated the association of grip strength with cataract and DR.<br><br>CONCLUSIONS: Weaker grip strength is associated with cataracts, glaucoma, and DR. Metabolomic alterations, especially disrupted lipid metabolism and omega-3 PUFA decrement, serve to be the critical mediators.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40634735,
year = {2025},
author = {Olivieri, C and Tibaldi, T and Berni, A and Eandi, CM and Neri, G and Fai, A and Viggiano, P and Marolo, P and Bandello, F and Reibaldi, M and Borrelli, E},
title = {Quantifying macular atrophy in neovascular AMD using en face structural OCT imaging.},
journal = {Eye (London, England)},
volume = {39},
number = {13},
pages = {2534-2539},
pmid = {40634735},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Prospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Atrophy ; Aged, 80 and over ; Reproducibility of Results ; Fluorescein Angiography ; *Macula Lutea/pathology ; Angiogenesis Inhibitors/therapeutic use ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Multimodal Imaging ; Visual Acuity ; },
abstract = {PURPOSE: To assess the reliability of en face swept-source OCT (SS-OCT) imaging for quantifying macular atrophy in patients with neovascular age-related macular degeneration (AMD) and evaluate its limitations compared to green autofluorescence (GAF) imaging.<br><br>METHODS: This prospective observational study included 30 patients with macular atrophy associated with neovascular AMD previously treated with anti-VEGF therapy. Multimodal imaging included GAF and en face SS-OCT. Macular atrophy was quantified as regions of hypoautofluorescence on GAF and hypertransmission defects (hyperTDs) on en face SS-OCT. Two masked graders measured atrophy size, followed by qualitative analysis of inter-modality discrepancies. Statistical comparisons were conducted using the Wilcoxon test and Spearman correlation.<br><br>RESULTS: Mean macular atrophy size was 5.96&#x2009;&#xb1;&#x2009;4.48&#x2009;mm&#xb2; on SS-OCT and 7.10&#x2009;&#xb1;&#x2009;5.47&#x2009;mm&#xb2; on GAF, with a significant difference (p&#x2009;<&#x2009;0.001) but strong correlation (&#x3c1;&#x2009;=&#x2009;0.998, p&#x2009;<&#x2009;0.001). Discrepancies arose due to hyperpigmentation obscuring hyperTDs and macular haemorrhages on SS-OCT underestimations of atrophy. Additionally, fibrosis also reduced choroidal hypertransmission, complicating hyperTD detection on SS-OCT. Border delineation inconsistencies were also observed, with diminished autofluorescence on GAF not always corresponding to hyperTDs on SS-OCT.<br><br>CONCLUSIONS: En face SS-OCT is a reliable imaging modality for quantifying macular atrophy in neovascular AMD, with strong correlation to GAF measurements. However, hyperpigmentation, fibrosis, haemorrhages, and variability in border delineation introduce significant challenges. These findings underscore the need for careful interpretation of atrophy metrics and highlight the importance of addressing inter-modality discrepancies in clinical and research applications.},
}
@article {pmid40634513,
year = {2025},
author = {Abbasi, R and Amin, F and Alabrah, A and Choi, GS and Khan, S and Bin Heyat, MB and Iqbal, MS and Chen, H},
title = {Diabetic retinopathy detection using adaptive deep convolutional neural networks on fundus images.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {24647},
pmid = {40634513},
issn = {2045-2322},
mesh = {*Diabetic Retinopathy/diagnostic imaging/diagnosis ; Humans ; *Fundus Oculi ; *Neural Networks, Computer ; *Image Processing, Computer-Assisted/methods ; Retina/diagnostic imaging ; Deep Learning ; *Image Interpretation, Computer-Assisted/methods ; Algorithms ; Convolutional Neural Networks ; },
abstract = {Diabetic retinopathy (DR) is an age-related macular degeneration eye disease problem that causes pathological changes in the retinal neural and vascular system. Recently, fundus imaging is a popular technology and widely used for clinical diagnosis, diabetic retinopathy, etc. It is evident from the literature that image quality changes due to uneven illumination, pigmentation level effect, and camera sensitivity affect clinical performance, particularly in automated image analysis systems. In addition, low-quality retinal images make the subsequent precise segmentation a challenging task for the computer diagnosis of retinal images. Thus, in order to solve this issue, herein, we proposed an adaptive enhancement-based Deep Convolutional Neural Network (DCNN) model for diabetic retinopathy (DR). In our proposed model, we used an adaptive gamma enhancement matrix to optimize the color channels and contrast standardization used in images. The proposed model integrates quantile-based histogram equalization to expand the perceptibility of the fundus image. Our proposed model provides a remarkable improvement in fundus color images and can be used particularly for low-contrast quality images. We performed several experiments, and the efficiency is evaluated using a large public dataset named Messidor's. Our proposed model efficiently classifies a distinct group of retinal images. The average assessment score for the original and enhanced images is 0.1942 (standard deviation: 0.0799), Peak Signal-to-Noise Ratio (PSNR) 28.79, and Structural Similarity Index (SSIM) 0.71. The best classification accuracy is [Formula: see text], indicating that Convolutional Neural Networks (CNNs) and transfer learning are superior to traditional methods. The results show that the proposed model increases the contrast of a particular color image without altering its structural information.},
}
@article {pmid40632993,
year = {2025},
author = {Sivaprasad, S and Fu, DJ and Faes, L},
title = {Evidence Generation in Intermediate Age-related Macular Degeneration: The 2025 Paul Henkind Memorial Lecture at Macula Society.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {2219-2223},
doi = {10.1097/IAE.0000000000004603},
pmid = {40632993},
issn = {1539-2864},
}
@article {pmid40632946,
year = {2025},
author = {Alshaikhsalama, AM and Alsoudi, AF and Wai, KM and Koo, E and Mruthyunjaya, P and Rahimy, E},
title = {GOUT AND RISK OF AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {2289-2296},
pmid = {40632946},
issn = {1539-2864},
mesh = {Humans ; *Gout/complications/drug therapy/epidemiology/diagnosis ; Retrospective Studies ; Male ; Female ; Aged ; Risk Factors ; Disease Progression ; Aged, 80 and over ; *Wet Macular Degeneration/epidemiology/diagnosis/etiology ; Middle Aged ; Visual Acuity ; Propensity Score ; Incidence ; Follow-Up Studies ; *Macular Degeneration/epidemiology/etiology/diagnosis ; United States/epidemiology ; },
abstract = {PURPOSE: To examine the association between gout and subsequent development and progression of age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective cohort study, a multicenter health care research network was used to identify patients with an International Classification of Diseases, 10th Revision for idiopathic gout and a prescription for uric acid-lowering agent (Gout cohort) compared with a matched cohort of patients without a diagnosis of gout (Control cohort) for ophthalmic outcomes. Propensity score matching was applied to balance baseline demographics and health status between cohorts.<br><br>RESULTS: Patients with gout had an increased risk of developing dry AMD (relative risk, 2.73, 95% confidence intervals, 2.30-3.25; P < 0.001), advanced dry AMD (relative risk, 2.64, 95% confidence intervals, 1.32-5.28; P < 0.001), wet AMD (relative risk, 2.48, 95% confidence intervals, 1.82-3.38; P < 0.001), and needing subsequent antivascular endothelial growth factor therapy (relative risk, 2.80, 95% confidence intervals, 2.14-3.67; P < 0.001) compared with those without gout at 5 years. Similar trends were observed among patients with early AMD and gout compared with those with early AMD without gout.<br><br>CONCLUSION: In a national multicenter database, an increased risk of AMD development and progression to advanced disease stages was found among patient with gout compared with controls. Additional investigation into the mechanisms and effects of hyperuricemia are necessary to clarify these associations.},
}
@article {pmid40632162,
year = {2025},
author = {Çalışkan, B},
title = {Metabolic stress in exudative age-related macular degeneration: potential role of lipid ındex.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {281},
pmid = {40632162},
issn = {1573-2630},
mesh = {Humans ; Female ; Male ; Retrospective Studies ; Aged ; *Lipids/blood ; *Wet Macular Degeneration/blood/diagnosis/metabolism ; Biomarkers/blood ; ROC Curve ; *Triglycerides/blood ; *Stress, Physiological/physiology ; Risk Factors ; Middle Aged ; Blood Glucose/metabolism ; Aged, 80 and over ; },
abstract = {PURPOSE: To evaluate serum lipid profiles with triglyceride-Glucose (TyG) and TG/HDL-c indices in patients with exudative type age-related macular degeneration.<br><br>METHODS: A total of 71 participants were included in the study: 35 with exudative AMD and 36 in the control group. Demographic, clinical, and laboratory data of all patients were analysed retrospectively. Serum lipid profiles and lipid indices were calculated and recorded (total cholesterol, LDL-c, HDL-c and triglycerides, TyG and TG/HDL-c). Statistical analyses, regression analyses, and ROC analysis were performed to compare all results.<br><br>RESULTS: Demographic and systemic comorbidities, including age, gender, hypertension, and history of cardiovascular disease, did not significantly differ between the groups (p&#x2009;>&#x2009;0.05). In comparison to the control group, the exudative AMD group's TyG index was considerably higher (p&#x2009;=&#x2009;0.038). Serum lipid profiles were not significantly different between groups (p&#x2009;>&#x2009;0.05). Logistic regression analysis showed that exudative type was a risk factor for the development of AMD based on the TyG index (OR&#x2009;=&#x2009;0.126, 95% CI: 0.017-0.940, p&#x2009;=&#x2009;0.043). ROC analysis suggested that the TyG index served as a moderate predictor of disease risk.<br><br>CONCLUSION: The TyG index may be substantially associated with the presence of exudative AMD and may serve as a valuable biomarker for clinical application. The relevance of metabolic stress in the development of AMD is emphasized by the lack of association with other lipid parameters. To confirm these findings, further large-scale studies are needed.},
}
@article {pmid40628339,
year = {2025},
author = {El-Mulki, OS and Berni, A and Kastner, J and Shen, M and Cheng, Y and Herrera, G and Beqiri, S and Trivizki, O and Le, VH and Sivathanu Kumar, B and Di Nicola, M and O'Brien, R and Waheed, NK and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {The Macular Burden of Calcified Drusen and the Onset of Large Choroidal Hypertransmission Defects in Intermediate AMD.},
journal = {American journal of ophthalmology},
volume = {278},
number = {},
pages = {402-412},
doi = {10.1016/j.ajo.2025.07.001},
pmid = {40628339},
issn = {1879-1891},
mesh = {Humans ; Tomography, Optical Coherence/methods ; Female ; Male ; *Retinal Drusen/diagnosis/complications ; Aged ; Prospective Studies ; Fluorescein Angiography/methods ; Follow-Up Studies ; Retrospective Studies ; *Calcinosis/diagnosis/complications ; Aged, 80 and over ; Visual Acuity/physiology ; *Choroid/pathology ; *Choroid Diseases/diagnosis/etiology ; Middle Aged ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; *Macular Degeneration/diagnosis ; *Macula Lutea/pathology ; },
abstract = {PURPOSE: This study used en face swept-source optical coherence tomography (SS-OCT) imaging to follow eyes with intermediate age-related macular degeneration (iAMD) in the presence and absence of calcified drusen (CaD) to determine if the presence and size of CaD increased the risk of forming large choroidal hypertransmission defects (hyperTDs).<br><br>DESIGN: Post hoc subgroup analysis of a prospective cohort study.<br><br>METHODS: Eyes with iAMD were enrolled in a prospective SS-OCT study, and the onset of large hyperTDs was retrospectively analyzed. Imaging was performed using 6 &#xd7; 6 mm SS-OCT angiography (SS-OCTA) scans at baseline and follow-up. Large hyperTDs were defined as bright lesions &#x2265;250 &#xb5;m in greatest linear dimension (GLD) on en face sub-retinal pigment epithelium (subRPE) slabs positioned 64 to 400 &#xb5;m beneath Bruch's membrane (BM). CaD were identified as drusen with heterogeneous internal reflectivity projecting choroidal hypotransmission defects (hypoTDs) on the same subRPE slabs. CaD were distinguished from hyperreflective foci (HRF) by analyzing corresponding B-scans. Two independent graders used a semiautomated algorithm to refine CaD outlines and reach consensus, with disagreements adjudicated by a senior grader. CaD area, HRF area, and drusen volume were measured within 5-mm fovea-centered circles.<br><br>RESULTS: Median follow-up time for the 171 eyes from 121 patients followed in this study was 59.1 months (95% CI: 52.0-67.8 months), and 82 eyes developed at least one large hyperTD during follow-up. The mean baseline CaD area measurement was 0.037 mm&#xb2; [range: 0-0.567 mm&#xb2;] in eyes that developed hyperTDs, while in eyes that did not, it was 0.008 mm&#xb2; [range: 0-0.360 mm&#xb2;] (P = .01). Drusen volume, HRF area, and CaD area were predictors for hyperTD onset when considered alone, but only HRF area (P < .001) and CaD area (P =.008) remained significant predictors for hyperTD onset when using a multivariable Cox regression analysis. Regardless of area, the presence of any CaD increased the risk of hyperTD formation (P < .001).<br><br>CONCLUSIONS: In a multivariable Cox regression analysis, the area measurements of CaD and HRF in eyes with iAMD were significant predictors of hyperTD onset, and the presence of any CaD increased the risk of hyperTD formation.},
}
@article {pmid40628205,
year = {2025},
author = {Souied, EH and Couturier, A and Devin, F and Creuzot-Garcher, C and Baillif, S and Weber, M and Ponthieux, A and Kodjikian, L},
title = {Functional and anatomic outcomes of brolucizumab in adults with neovascular age-related macular degeneration - The OCTOPUS cohort study.},
journal = {Journal francais d'ophtalmologie},
volume = {48},
number = {7},
pages = {104583},
doi = {10.1016/j.jfo.2025.104583},
pmid = {40628205},
issn = {1773-0597},
mesh = {Humans ; Female ; Aged ; Male ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use/adverse effects ; Middle Aged ; Treatment Outcome ; Aged, 80 and over ; Visual Acuity/drug effects ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/pathology ; Cohort Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/adverse effects ; Intravitreal Injections ; *Macular Degeneration/drug therapy/pathology ; *Choroidal Neovascularization/drug therapy/pathology ; },
abstract = {PURPOSE: To evaluate the functional and anatomic outcomes of brolucizumab in treatment-naïve adults (≥50years) with neovascular age-related macular degeneration.<br><br>METHODS: This was a single-arm, open-label, multicenter study. Patients (n=210) were treated with brolucizumab 6mg at Weeks (W) 0, 4 and 8, then every 12weeks (q12w) or 8weeks (q8w) depending on disease activity. The primary endpoint was change in the area of the CNV lesion from baseline to Week 12, as measured by OCTA. Functional and anatomic outcomes were evaluated up to Week 48.<br><br>RESULTS: Mean age was 77.8years; 61.4% were female. CNV lesion size decreased from baseline to Week 12 by 79.3% and to W48 by 68.5%. Mean (SD) BCVA increased from baseline to Week 48 by 8.3 (12.0) letters, and disease activity was absent for 77.4% of patients at W48. There was a mean (SD) decrease from baseline in CSFT (&#x3bc;m) of -151&#x3bc;m (&#xb1;134) at Week 48, with most patients (62.3%) having no retinal fluid (23.9% had IRF, 16.4% had SRF, and 11.9% had sub-RPE fluid). Confirmed intraocular inflammation occurred in 24 patients, mostly during loading, and did not compromise gains in BCVA.<br><br>CONCLUSIONS: CNV lesion size as assessed by OCTA decreased with brolucizumab, which also led to vision gains and better anatomic outcomes.},
}
@article {pmid40627958,
year = {2025},
author = {Rajendran, N and Runyon, W and Hu, S and Singh, A and Ratnapriya, R and Kumar, R and Csaky, K and Sripathi, SR},
title = {Generation of induced pluripotent stem cell lines (RFSCi003-A, RFSCi004-A) from monozygotic twins discordant for age-related macular degeneration.},
journal = {Stem cell research},
volume = {87},
number = {},
pages = {103768},
doi = {10.1016/j.scr.2025.103768},
pmid = {40627958},
issn = {1876-7753},
mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/cytology/pathology ; *Macular Degeneration/pathology/genetics/metabolism ; *Twins, Monozygotic ; Cell Line ; Male ; Female ; Leukocytes, Mononuclear/cytology ; },
abstract = {Age-related macular degeneration (AMD) has significant genetic component, yet monozygotic twins frequently exhibit discordance in disease status, highlighting the role of non-genetic factors. To enable comparative studies of AMD pathogenesis, we generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of a monozygotic twin pair discordant for AMD. These iPSC lines offer a unique genetically matched resource to investigate molecular differences between affected and unaffected twins, as well as their responses to genetic, epigenetic, and environmental contributors to AMD development.},
}
@article {pmid40626808,
year = {2025},
author = {Notomi, S and Wu, G and Nagaoka, T and Yotsumoto, N and Araki, T and Arima, M and Hisatomi, T and Sonoda, KH and Sawada, K},
title = {Intravenous Sodium Iodate Administration Induces Macula-Specific RPE Damage and Rod-Dominant Apoptosis in the Cynomolgus Monkey.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {9},
pages = {18},
pmid = {40626808},
issn = {1552-5783},
mesh = {Animals ; Macaca fascicularis ; Male ; *Retinal Pigment Epithelium/drug effects/pathology/ultrastructure ; *Apoptosis/drug effects ; Tomography, Optical Coherence ; *Iodates/toxicity/administration &amp; dosage ; Fluorescein Angiography ; Disease Models, Animal ; *Retinal Rod Photoreceptor Cells/drug effects/pathology ; Injections, Intravenous ; *Macula Lutea/drug effects/pathology ; Microscopy, Electron, Transmission ; Retinal Degeneration/chemically induced/pathology ; },
abstract = {PURPOSE: Although sodium-iodate (SI)-induced retinal degeneration has been extensively studied in rodent models, its macular pathology and cone/rod vulnerability difference remains elusive. This study aims to characterize SI-induced macular pathology in cynomolgus monkeys.<br><br>METHODS: Intravenous injections of SI were performed on four male cynomolgus monkeys including three young adults (Animal No.&#xa0;1-3; five to six years old) and one juvenile (Animal No.&#xa0;4; two years old) from a breeding colony. To optimize dosing, Animal No.&#xa0;1 received 25 and 37.5&#xa0;mg/kg SI; Animal No.&#xa0;2 received a single SI dose (30&#xa0;mg/kg) to confirm reproducibility. Animal No.&#xa0;3 was used to examine subclinical effects at a lower dose (25&#xa0;mg/kg). Animal No.&#xa0;4 received increasing doses (30, 35, and 40&#xa0;mg/kg). Retinal changes were evaluated using fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). Histological analysis and transmission electron microscopy (TEM) were also performed.<br><br>RESULTS: In Animal No.&#xa0;1, prominent fluorescein leakage by FA and RPE elevation on OCT was observed in the macula after 37.5&#xa0;mg/kg SI. Histology and TEM revealed that elevated RPE lesion was accompanied by significant RPE migration. Animal No.&#xa0;2 exhibited similar retinal degeneration. Animal No.&#xa0;3 exhibited no RPE barrier disruption but showed outer segment damage and RPE melanolipofuscin accumulation. Animal No.&#xa0;4 showed minimal macular degeneration despite escalating doses. In the peripheral retina, rod apoptosis was evident, whereas macular cone cell death was limited even at high doses.<br><br>CONCLUSION: Systemic SI administration can induce macular degeneration with RPE barrier disruption in young-adult monkeys, supporting a macula- and cell-type-specific vulnerability.},
}
@article {pmid40626807,
year = {2025},
author = {Alhelaly, M and Soylu, C and Corradetti, G and Corvi, F and Mahmoudi, A and Abbasgholizadeh, R and Bellisario, G and He, Y and Quarta, A and Nittala, MG and Staurenghi, G and Sadda, SR},
title = {In Vivo Characterization of Bruch's Membrane Breaks in Neovascular Age-Related Macular Degeneration Using High-Resolution Optical Coherence Tomography.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {9},
pages = {19},
pmid = {40626807},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Bruch Membrane/pathology ; Female ; Male ; Aged ; Visual Acuity/physiology ; *Wet Macular Degeneration/diagnosis/drug therapy/pathology ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Fluorescein Angiography ; *Choroidal Neovascularization/diagnosis ; Middle Aged ; Retrospective Studies ; Follow-Up Studies ; },
abstract = {PURPOSE: The purpose of this study was to investigate the frequency and characteristics of Bruch's membrane (BM) breaks, and their relationship with clinically relevant outcomes in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Forty-seven eyes (39 patients) with nAMD and type 1 macular neovascularization (MNV) were imaged using high-resolution optical coherence tomography (High-Res OCT; Heidelberg). Foveal-centered 20 degrees &#xd7; 20 degrees volume scans (1024 &#xd7; 97, automated real time [ART] = 5-25) were obtained. BM breaks, defined as definite interruptions in the hyper-reflective BM band, were identified within the MNV region. The maximum break extent was measured. Break density, distribution, and eccentricity were also evaluated. BM break parameters were correlated with visual acuity and number of intravitreal injections.<br><br>RESULTS: Thirty eyes were included for quantitative analysis. Multiple breaks were observed in 76.7% of eyes, with a mean of 4.30 &#xb1; 4.15 breaks/eye. Notably, breaks showed a preferential eccentric distribution, tending to be closer to the lesion border (mean eccentricity ratio = 4.33 &#xb1; 3.61). Our model suggested that a higher break count was significantly associated with higher injection number (P = 0.042), whereas a greater break length was associated with fewer injections (P = 0.001). There was a trend for a higher break count to be associated with better BCVA, but this was not statistically significant (P = 0.099).<br><br>CONCLUSIONS: Most MNV lesions demonstrated multiple breaks with a tendency for breaks to be in the lesion periphery. The identification of BM breaks appeared to be of clinical relevance as the number and length of the breaks were associated with the number of intravitreal injections. Larger prospective studies are warranted to confirm these findings.},
}
@article {pmid40626613,
year = {2025},
author = {Cho, IH and Park, M and Ma, DJ and Hong, IH and Kim, H and Kim, SH},
title = {Continuity of care and risk of vision loss in patients with newly developed macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.17547},
pmid = {40626613},
issn = {1755-3768},
support = {//Soonchunhyang University Research Fund/ ; RS2023-00245657//National Research Foundation of Korea/ ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (AMD) is a major cause of vision loss. Effective treatment requires sustained care, which may be influenced by continuity of care (COC). Understanding this association is crucial for improving patient outcomes. We investigated the association between COC and the risk of visual impairment in patients newly diagnosed with neovascular AMD.<br><br>METHODS: This nationwide cohort study sourced data from the South Korean National Health Insurance Service database (2014-2021). In total, 15&#x2009;563 (6210 females) newly diagnosed patients with neovascular AMD were included. The COC index, based on the frequency of ophthalmology visits over the first 2&#x2009;years post-diagnosis, was assessed; a threshold of 0.75 was used to define good continuity. The primary outcome was visual impairment. Statistical models were used to assess the association between COC and the visual impairment risk, with adjustment for relevant confounding variables.<br><br>RESULTS: Patients with a bad COC index had a significantly higher cumulative incidence (6.86% vs. 4.78%) and a higher incidence rate of visual impairment (909 vs. 704 cases per 100&#x2009;000 person-years; 95% confidence interval, 764.0-1080.4, p&#x2009;<&#x2009;0.001). This elevated risk was especially notable for female patients, patients aged &#x2265;70&#x2009;years, and patients with lower comorbidity burdens.<br><br>CONCLUSIONS: Poor COC is associated with increased visual impairment risk in patients with neovascular AMD. Strategies to improve COC may reduce this risk, particularly among older adults and high-risk groups.},
}
@article {pmid40625502,
year = {2025},
author = {Gupta, D and Chawla, S},
title = {Association of Apolipoprotein E (APOE) Gene Polymorphism With Age-Related Macular Degeneration (AMD) in Indian Patients.},
journal = {Cureus},
volume = {17},
number = {6},
pages = {e85441},
pmid = {40625502},
issn = {2168-8184},
abstract = {Background Age-related macular degeneration (AMD or ARMD; Online Mendelian Inheritance in Man (OMIM) #603075) is the degenerative disease of the retina that causes progressive impairment of central vision, leading to irreparable vision loss in older persons. Objective The objective was to investigate the association between apolipoprotein E (APOE) gene polymorphism and AMD in Indian patients. Materials and methods Genotyping for APOEvariants was performed in 121 AMD patients and 100 healthy controls using a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method, followed by sequencing. Genotype and allele were analyzed using the allele counting method. P-value < 0.05 was considered statistically significant. Results The E3/E3 genotype has a frequency of 76/100 (76%) in controls and 97 (80%) in AMD. The frequency of the heterozygous E2/E2 genotype was 19 (19%) in controls and eight (6.6%) in AMD, and the variant E4/E4 genotype was found in one control (1%) and in one AMD case (1%). Some protective effect of the E2/E2 heterozygous genotype is seen (OR = 0.30; P-value = 0.009). Wild allele E3 in controls was 155 (77.5%) in AMD 209 (86.3%), E2 allele 41 (20.5%), and 17 (7%) in controls and AMD. E4 alleles in controls were four (2%) and 16 (6.6%) in AMD. E2 allele showed a protective effect; we did not find any significant association in APOE variant genotypes, and the odds ratios were within a 95% confidence interval (95% CI). As independent risk factors for AMD, logistic regression (LR) analysis was applied using E2, E3, and E4 alleles and their genotypes. Conclusion This study raises the possibility that the APOE gene might not have a significant association with AMD in Indian patients. However, our sample statistics suggest that the APOE E4 allele may be a risk factor for AMD in the Indian population. The study requires verification in a large sample size, across different parts of the country, and among other ethnic groups.},
}
@article {pmid40625041,
year = {2025},
author = {Kim, MS and Nam, S and Park, SJ and Lee, J and Woo, SJ},
title = {10-Year Change and Projection in Prevalence and Incidence of Exudative Age-Related Macular Degeneration in Korea.},
journal = {Journal of Korean medical science},
volume = {40},
number = {26},
pages = {e128},
pmid = {40625041},
issn = {1598-6357},
support = {RS-2023-00248480/NRF/National Research Foundation of Korea/Korea ; RS-2023-00210974/NRF/National Research Foundation of Korea/Korea ; },
mesh = {Humans ; Republic of Korea/epidemiology ; Male ; Female ; Incidence ; Middle Aged ; Aged ; Prevalence ; *Macular Degeneration/epidemiology/diagnosis ; Aged, 80 and over ; Adult ; Databases, Factual ; },
abstract = {BACKGROUND: Updating the recent epidemiology of exudative age-related macular degeneration (AMD) is crucial for understanding the epidemiological trend of the disease, preparing healthcare strategies, and providing data for global comparisons. This study aimed to estimate the nationwide trend in prevalence and incidence of exudative AMD in Korea.<br><br>METHODS: In this nationwide population-based study using the National Health Insurance Service data, patients who have registration code for exudative AMD and aged 40 years or older were extracted from 2013 to 2022. Cumulative prevalence from 2013 onwards, annual prevalence, and incidence was estimated per 10,000 people. We also calculated age-standardized estimates using the World Health Organization population proportions. Linear regression to test time trend was performed. The annual prevalence and incidence were predicted using time series analysis.<br><br>RESULTS: The crude cumulative prevalence of exudative AMD was 42.7 in 2022, with men having a higher prevalence than women (51.3 vs. 34.6). The annual prevalence rose from 10.7 in 2013 to 22.5 in 2022 (age-standardized, P < 0.001). The incidence consistently increased from 2.8 in 2013 to 4.7 in 2022 (age-standardized, P = 0.001), with higher incidence in men than in women. The prevalence and incidence of exudative AMD were higher in older age groups and showed a faster increase with advancing age. The predicted annual prevalence and incidence of exudative AMD in 2040 are 46.2 and 8.4, respectively. The crude cumulative number of patients was 127,044 in 2022 and is projected to reach 230,899 in 2030 and 374,282 in 2040.<br><br>CONCLUSION: The prevalence and incidence of exudative AMD in Korea has been increased annually, especially in the elderly group. With the Korean and global population aging, there will be a growing burden from visual impairment and medical expenses associated with exudative AMD.},
}
@article {pmid40624086,
year = {2025},
author = {Yanagida, K and Miura, M and Noma, H and Mino, T and Azuma, S and Seesan, T and Makita, S and Yasuno, Y},
title = {Evaluation of retinal pigment epithelium changes in serous pigment epithelial detachment using synthesized multi-contrast polarization-sensitive optical coherence tomography.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {24304},
pmid = {40624086},
issn = {2045-2322},
support = {21K09684//Japan Society for the Promotion of Science/ ; 21H01836//Japan Society for the Promotion of Science/ ; 24K12753//Japan Society for the Promotion of Science/ ; JPMJMI18G8//Japan Science and Technology Agency/ ; JPMJCR2105//Japan Science and Technology Agency/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/diagnostic imaging/pathology/metabolism ; Female ; Male ; *Retinal Detachment/diagnostic imaging/pathology ; Aged ; Melanins/metabolism ; Middle Aged ; Macular Degeneration/complications/diagnostic imaging/pathology ; Aged, 80 and over ; },
abstract = {Retinal pigment epithelium (RPE) melanin thickness maps, derived from multi-contrast images-including the degree of polarization uniformity (DOPU), optical coherence tomography (OCT) angiography, and the attenuation coefficient-are obtained using multi-contrast polarization-sensitive OCT (PS-OCT). These maps have demonstrated utility for three-dimensional assessment of changes in melanin within the RPE (RPE-melanin). While both OCT angiography and the attenuation coefficient can be derived from conventional OCT, measuring the DOPU requires PS-OCT, which is not available on standard commercial OCT systems. To overcome this limitation, we utilized a convolutional neural network to generate DOPU-like images from standard OCT images and used these to calculate a synthesized RPE-melanin thickness map. We evaluated 22 eyes from 20 patients with serous pigment epithelial detachment (PED) secondary to age-related macular degeneration. Both original and synthesized RPE-melanin thickness maps were calculated from multi-contrast PS-OCT datasets. Active RPE lesions were defined as areas with RPE-melanin thickness of ≥ 70 μm (originalRPE70 and synRPE70 for the original and synthesized maps, respectively). Both synthesized and original RPE-melanin thickness maps closely resembled near-infrared autofluorescence imaging. Furthermore, both the originalRPE70 area and synRPE70 area were significantly positively correlated with the PED volume. Synthesized RPE-melanin thickness maps may be useful for clinical quantification of RPE-melanin.},
}
@article {pmid40623731,
year = {2025},
author = {Singh, RP and Weng, CY and Kitchens, JW and Quilantan, J and Schwartz, R and Baumal, CR and Goldberg, RA},
title = {Consideration of patient phenotypes in geographic atrophy due to age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40623731},
issn = {2397-3269},
mesh = {Humans ; *Geographic Atrophy/diagnosis/etiology ; Phenotype ; *Macular Degeneration/complications/diagnosis ; Disease Progression ; Tomography, Optical Coherence/methods ; Risk Factors ; Fluorescein Angiography/methods ; },
abstract = {Geographic atrophy (GA) is a form of advanced age-related macular degeneration (AMD) affecting approximately 1 million people in the USA and 5 million globally. In this review, retinal imaging techniques used for diagnosis and monitoring progression of GA in AMD, and the risk factors associated with the development and progression of GA are summarised. To familiarise clinicians with common phenotypes of patients with GA, the clinical and imaging features that may lead to rapid progression of GA in various phenotypes are highlighted. With the recent US Food and Drug Administration approval of new GA treatments that reduce lesion growth, understanding the risk of progression to GA and factors contributing to GA growth may aid in patient selection and guide patient-level management and treatment.},
}
@article {pmid40623726,
year = {2025},
author = {Zhang, W and Ji, W and Cheng, M and Xue, H and Peng, C and Li, W and Ma, L and Zhang, W and Ji, X and Zhang, Z},
title = {Nanozymes in the Repair of Fundus Damage.},
journal = {ACS applied materials &amp; interfaces},
volume = {17},
number = {28},
pages = {39880-39899},
doi = {10.1021/acsami.5c07979},
pmid = {40623726},
issn = {1944-8252},
mesh = {Humans ; Animals ; *Nanostructures/chemistry/therapeutic use ; Oxidative Stress/drug effects ; *Fundus Oculi/drug effects ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Diabetic Retinopathy/drug therapy/metabolism/pathology ; Reactive Oxygen Species/metabolism ; *Retinal Neovascularization/drug therapy/metabolism ; },
abstract = {Ocular diseases associated with fundus damage, such as age-related macular degeneration, diabetic retinopathy, and retinal neovascularization, represent significant contributors to severe vision impairment globally. Traditional treatment methods often face challenges, including low drug delivery efficiency, poor bioavailability, and substantial side effects. Nanozymes, a class of enzymatically active nanomaterials, have recently emerged as a promising therapeutic approach to ocular diseases. These nanozymes can effectively alleviate oxidative stress, modulate local immune responses, and inhibit pathological angiogenesis by scavenging reactive oxygen species and regulating inflammasome activation. This review aims to elucidate the mechanisms of action of various types of nanozymes as well as the pathophysiological mechanisms underlying ocular diseases that cause fundus damage. Furthermore, it discusses recent advancements in the use of nanozymes for treating fundus-related ocular disorders. Finally, this review highlights the current limitations and future directions for nanozymes in the treatment of fundus injury-associated diseases.},
}
@article {pmid40619442,
year = {2025},
author = {Mares, V and Reiter, GS and Feitosa, A and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U and Nehemy, MB},
title = {Automated fluid monitoring to optimize the follow-up of neovascular age-related macular degeneration patients in the Brazilian population.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {75},
pmid = {40619442},
issn = {2056-9920},
abstract = {OBJECTIVES: To investigate the efficacy of an artificial intelligence (AI)-based fluid monitoring tool in optimizing the monitoring of neovascular age-related macular degeneration (nAMD) patients in a Brazilian cohort.<br><br>METHODS: This is a retrospective real-world study performed in a tertiary center in Brazil, including patients with nAMD. Spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, Germany) images were processed at baseline and over 2 years of follow-up. Demographic and clinical data were collected. A deep learning algorithm (Fluid Monitor, RetInSight, Austria) was used to automatically quantify intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED). A longitudinal panel regression model and Log-Rank test were performed to assess the correlation between fluid volumes and treatment frequency, visual outcomes, macular atrophy (MA) and subretinal fibrosis (SF) development.<br><br>RESULTS: Ninety-nine eyes from 84 patients were included. Fifty-eight eyes were treatment-na&#xef;ve. Higher IRF and PED in the 6&#xa0;mm area were correlated with worse visual outcomes over a 2-year follow-up (p&#x2009;=&#x2009;0.01 and p&#x2009;<&#x2009;0.001, respectively). Higher IRF, SRF and PED were correlated with an increased risk of SF development (p&#x2009;<&#x2009;0.001, p&#x2009;=&#x2009;0.049 and p&#x2009;=&#x2009;0.02 respectively). MA development showed no significant correlation with higher IRF, SRF nor PED in this analysis. Higher SRF volume correlated with a greater number of required intravitreal injections over 2-years.<br><br>CONCLUSION: This study investigates the multifaceted landscape of nAMD in a tertiary center in the Southeast Brazil using an AI-based fluid monitoring tool. Further studies that highlight the significance of using newly validated technologies across diverse populations worldwide will be of interest.},
}
@article {pmid40619423,
year = {2025},
author = {Lei, S and Liu, Y},
title = {Identifying the important involvement of cuproptosis in the pathophysiology of age-related macular degeneration.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {583},
pmid = {40619423},
issn = {2047-783X},
support = {WX23Z33//The Funding for Scientific Research Projects from Wuhan Municipal Health Commission/ ; WX23Z33//The Funding for Scientific Research Projects from Wuhan Municipal Health Commission/ ; },
mesh = {*Macular Degeneration/genetics/physiopathology/pathology ; Animals ; Mice ; Humans ; Apoptosis/genetics ; Disease Models, Animal ; Gene Expression Profiling ; Retinal Pigment Epithelium/pathology/metabolism ; Transcriptome ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a neurodegenerative disease associated with severe visual impairment in the elders. Despite recent studies and advances, the pathophysiology underlying the development of AMD is still not fully understood, and current therapies remain limited. Programmed cell death (PCD) has been implicated in neurodegenerative diseases. Therefore, the aim of this study is to investigate and identify key types of PCD and PCD-related genes involved in the pathogenesis of age-related macular degeneration (AMD).<br><br>METHODS: This study employs transcriptomic analyses and animal experiments. For bulk tissue transcriptomic analysis, the enrichment scores of PCD forms in AMD samples were calculated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. Single-cell transcriptomic analysis was conducted to examine the expression of PCD-related genes across different cell types. A mouse model was used to evaluate the therapeutic effects of a copper chelator on AMD.<br><br>RESULTS: Enrichment analysis indicated that cuproptosis was the most enriched type of PCD process in both AMD-affected macular and retinal pigment epithelium (RPE) samples. In addition, cuproptosis was associated with the progression of AMD. Single-cell transcriptomic analysis revealed that cuproptosis was highly activated in varies retinal cells from AMD samples when compared to normal ones. Pathway enrichment analysis showed that cuproptosis was associated with angiogenesis, inflammation, and cellular senescence in AMD. Furthermore, the copper chelator demonstrated a protective effect on retinal function in the AMD mouse model.<br><br>CONCLUSIONS: Our findings identified an important role of cuproptosis in the pathophysiology of AMD and suggested the potential of cuproptosis as a therapeutic target for AMD.},
}
@article {pmid40618781,
year = {2025},
author = {Ghaseminejad, F and Eden, K and Hopman, WM and Bona, M},
title = {Effectiveness of assistive devices in improving reading performance in vision rehabilitation patients.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2025.06.008},
pmid = {40618781},
issn = {1715-3360},
abstract = {OBJECTIVE: To evaluate the effectiveness of assistive devices in improving the reading performance of patients in a vision rehabilitation clinic.<br><br>METHODS: This is a prospective observational cohort study of patients referred to a hospital-based, urban, vision rehabilitation clinic in Southeastern Ontario. Patient demographics, ophthalmic diagnoses, and reading performance were investigated. Median reading speeds in words per minute (wpm) were compared with and without assistive devices, using the Minnesota Reading tool (MNRead). The relationships between improvement in reading speed and MNRead components (i.e., reading acuity, critical print size, and reading accessibility index), visual acuity, age, level of education, and previous exposure to vision rehabilitation were assessed. Subgroup analyses of patients diagnosed with age-related macular degeneration (AMD) and glaucoma were carried out.<br><br>RESULTS: A total of 199 patients were included in this study, with 71.9% over the age of 65. Most self-identified as female (68.8%) and Caucasian (93.0%). The median improvement in reading speed with assistive devices was 39.5 wpm (P < 0.001). Improvement in reading speeds was positively correlated with visual acuity (P&#x202f;=&#x202f;0.005) and inversely correlated with patients' age (P&#x202f;=&#x202f;0.029). Patients with glaucoma experienced a more substantial increase in reading speed (66.2 wpm) with assistive devices compared to AMD (38.0 wpm). Handheld magnifiers were significantly more effective in AMD patients, as compared to glaucoma.<br><br>CONCLUSIONS: This study provides an overview of a group of patients accessing vision rehabilitation interventions. We use the MNRead-based reading speed assessment to demonstrate the varying effectiveness of assistive devices across different patient groups.},
}
@article {pmid40617952,
year = {2025},
author = {Haas, AM and Kickinger, S and Stattin, M and Ahmed-Balestra, D and Jacob, M and Krepler, K and Ansari-Shahrezaei, S},
title = {Short-term natural history of macular neovascularization in nonexudative age-related macular degeneration using multimodal imaging.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {24070},
pmid = {40617952},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; Aged ; *Multimodal Imaging/methods ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging/pathology ; Retrospective Studies ; Aged, 80 and over ; Fluorescein Angiography ; Case-Control Studies ; Middle Aged ; *Choroidal Neovascularization/diagnostic imaging/pathology ; Disease Progression ; },
abstract = {The short-term conversion rate of a non-exudative macular neovascularization (ne-MNV) to an exudative stage in age-related macular degeneration (AMD) was evaluated in a single-center, retrospective case control study and associated imaging characteristics described, using multimodal imaging. A total of 241 Caucasian patients with unilateral, treatment-naive exudative neovascular AMD were screened for the presence of a ne-MNV in the fellow eye between March 2016 and May 2022. Eyes with a confirmed ne-MNV on indocyanine green angiography and/or optical coherence tomography angiography (OCTA) were monitored using structural OCT for signs of exudation. The main outcome was to evaluate multimodal imaging biomarkers to identify predictors of exudative conversion.Among 241 study eyes, 40 (16.6%) showed ne-MNV at baseline, all classified as type 1 MNV. During follow-up, 13 patients (32.5%) progressed to an exudative stage, with a mean time to exudation of 12.6 months (range: 2.6-22.4 months). The presence of a shallow irregular retinal pigment epithelial elevation (SIRE) was the only statistically significant feature associated with an increased risk of conversion to exudation. (p = 0.012) Patients with ne-MNV and a baseline SIRE are at increased risk for exudation. SIRE can be easily identified and followed up with structural OCT, providing a valuable marker for monitoring ne-MNV activation.},
}
@article {pmid40614931,
year = {2025},
author = {Barikian, A and Kumar, JB and McCullough, AJ and Silva, FQ and Sherman, S and Tanenbaum, K and Moini, H and Singh, RP},
title = {Characteristics and Outcomes of Patients with Neovascular Age-Related Macular Degeneration by Anti-VEGF Exposure in United States Clinical Practice.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.06.016},
pmid = {40614931},
issn = {2468-6530},
abstract = {OBJECTIVE: To assess 1-year visual outcomes of patients in routine clinical practice treated with ≥7 anti-VEGF injections for neovascular age-related macular degeneration (nAMD), baseline characteristics associated with receiving ≥7 anti-VEGF injections, and impact of treatment exposure on visual outcomes.<br><br>DESIGN: Retrospective analysis.<br><br>PARTICIPANTS: Treatment-naive eyes with baseline best-corrected visual acuity (BCVA) &#x2265;20/400, from patients aged &#x2265;55 years with nAMD diagnosed from January 1, 2013 to December 31, 2019.<br><br>METHODS: This analysis included eyes from the American Academy of Ophthalmology IRIS Registry&#xae; (Intelligent Research in Sight). Visual outcomes were evaluated by treatment exposure (&#x2265;7 or <7 intravitreal anti-VEGF injections) through year 1. Baseline factors associated with &#x2265;7 anti-VEGF injections and impact of treatment exposure on visual outcomes were evaluated by logistic regression.<br><br>MAIN OUTCOME MEASURES: Best-corrected visual acuity change from baseline by treatment exposure, association between baseline factors and treatment exposure, and magnitude of BCVA change by baseline factors and treatment exposure at year 1.<br><br>RESULTS: Of 295&#x2009;561 eligible eyes, 184&#x2009;258 actively treated were analyzed (&#x2265;7 anti-VEGF injections: 109&#x2009;696 eyes [59.5%]; <7 injections: 74&#x2009;562 eyes [40.5%]). At year 1, eyes receiving &#x2265;7 injections achieved greater BCVA gains versus those receiving <7 injections (least squares mean change [95% confidence interval]: +3.4 [3.3-3.5] vs. -0.2 [-0.3 to 0.0] letters). Asian or Black race (vs. White); Hispanic ethnicity (vs. non-Hispanic or Latino); Medicaid insurance (vs. Medicare); and treatment by a nonretina specialist were associated with lower odds of receiving &#x2265;7 injections. For both treatment exposure groups, BCVA <20/200 to 20/400 (vs. 20/100-20/200) was associated with greater visual gains, whereas BCVA >20/80, age &#x2265;85 years (vs. 75-84 years), treatment by a nonretina specialist, and Medicaid insurance were associated with lower BCVA gains.<br><br>CONCLUSIONS: Over one-third of newly diagnosed eyes with nAMD received <7 anti-VEGF injections and experienced worse visual outcomes at year 1 versus eyes receiving &#x2265;7 injections. Race, insurance type, and physician specialty impacted treatment exposure in nAMD management, whereas age, baseline BCVA, and insurance type impacted visual outcomes regardless of treatment exposure.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40614337,
year = {2025},
author = {Wang, E and Doig, GS and Ly, A},
title = {An enhanced educational intervention for improving confidence in the eye health benefits of appropriate care for age-related macular degeneration: a randomized controlled trial.},
journal = {Health education research},
volume = {40},
number = {4},
pages = {},
pmid = {40614337},
issn = {1465-3648},
support = {//Australian Government Research Training Program Scholarship/ ; //Commonwealth of Australia/ ; //Novartis Pharmaceuticals Australia/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Macular Degeneration/therapy/psychology ; Single-Blind Method ; *Patient Education as Topic/methods ; Aged, 80 and over ; Middle Aged ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Appropriate care is available for patients, reducing the risk of AMD progression. Unfortunately, patients do not always receive appropriate eye care. Our study aimed to develop and evaluate an enhanced educational intervention focused on the health benefits expected from receiving appropriate eye care for AMD. We conducted a randomized, single-blind, controlled trial between May 2022 and October 2023 at an intermediate-tier not-for-profit clinic, the Centre for Eye Health. We recruited 137 patients previously diagnosed with intermediate or advanced (neovascular, geographic atrophy) AMD. Patients were enrolled and randomized (68 enhanced education, 69 standard care). On the intention-to-treat analysis, there was no significant difference between groups with regards to the primary outcome, confidence in the eye health benefits of AMD-related care at 6 months (P = .25). On a priori-defined subgroup analysis, enhanced education resulted in a clinically meaningful and statistically significant differential improvement in confidence in the eye health benefits of AMD-related care for patients who were diagnosed with AMD less than 5 years ago (Pinteraction = .036). Further study is needed to confirm whether enhanced education can improve confidence in eye health care benefits for newly diagnosed AMD patients. Trial registration: anzctr.org.au Identifier: ACTRN12622000984796.},
}
@article {pmid40614029,
year = {2025},
author = {Wen, M and Xu, Q and Xie, J and Wu, R and Chen, X and Wen, N and Huang, S},
title = {Therapeutic potential of P2X7 receptor in retinal diseases.},
journal = {Purinergic signalling},
volume = {21},
number = {4},
pages = {863-871},
pmid = {40614029},
issn = {1573-9546},
mesh = {Humans ; *Receptors, Purinergic P2X7/metabolism ; *Retinal Diseases/drug therapy/metabolism ; Animals ; *Purinergic P2X Receptor Antagonists/therapeutic use/pharmacology ; },
abstract = {Retinal diseases affect the health of millions of people worldwide and activated P2X7 receptors (P2X7Rs) are associated with the pathophysiology of a variety of retina-related diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Increasing evidence indicated that P2X7R is over-activated in retinopathy and is involved in the occurrence and development of diabetic retinopathy. Purine vasotoxicity caused by over-activation of P2X7R can lead to decreased retinal blood flow and vascular dysfunction and activation of P2X7R can lead to the production of a large number of inflammatory factors, causing local inflammatory cells to infiltrate and form a vascular microenvironment, thus constituting the pathophysiological basis for the occurrence and development of retinopathy. A variety of P2X7R antagonists have been studied in clinical trials as potential treatments for retinal diseases. However, currently no P2X7R antagonists has been approved for retina diseases. In this review, we mainly focus on recent progress on the involvement of P2X7R in retinal diseases and its therapeutic potential in the future.},
}
@article {pmid40613237,
year = {2025},
author = {Wang, H and Ding, R and Jiang, W and Li, S and Wu, Y and Mao, J and Chen, Y and Sun, P and Shi, M},
title = {Effects of anti‑VEGF on peripapillary retinal nerve fiber layer and papillary/peripapillary blood circulation in retinopathies (Review).},
journal = {International journal of molecular medicine},
volume = {56},
number = {3},
pages = {},
pmid = {40613237},
issn = {1791-244X},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Retinal Diseases/drug therapy/pathology ; *Nerve Fibers/drug effects/pathology ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; },
abstract = {Vascular endothelial growth factor (VEGF) is an endothelial cell‑specific angiogenic factor. VEGF is involved in vasodilatation, nerve protection and retinal development and maturation. Over‑expression of VEGF is closely associated with retinopathies, such as retinal vein occlusion, diabetic retinopathy, age‑related macular degeneration and diabetic macular edema. Intravitreal injections of anti‑VEGFs are widely used in the treatment of retinopathies to reduce the angiogenesis and the macular edema. Hypothetically, repeated anti‑VEGF injections for retinopathies should interfere with the neuroprotective function of VEGF and might induce the vasoconstriction with a subsequent decrease in the ocular perfusion. These two could affect the optic nerve. The peripapillary retinal nerve fiber layer (p‑RNFL) thinning and the decreased papillary/peripapillary blood circulation can show the optic nerve damage earlier. In the present review, the effects of anti‑VEGFs on p‑RNFL and papillary/peripapillary blood circulation in retinopathies were comprehensively summarized and analyzed to explore whether the anti‑VEGFs cause damages to the optic nerve. The present review provided a detailed evaluation and analysis of the changes in p‑RNFL thickness, papillary/peripapillary blood circulation and intraocular pressure and the correlations between these changes with the number and type of anti‑VEGFs in 3,078 affected eyes and 520 fellow eyes with retinopathies. The present review sought to establish a foundation for the intravitreal administration of anti‑VEGFs and efficacy monitoring of the possible side effects on the optic nerve.},
}
@article {pmid40612577,
year = {2025},
author = {Ye, L and Huang, X and Xu, Y},
title = {Global trends and disparities in burden of blindness and vision loss caused by non-communicable diseases from 1990 to 2021, and forecasts to 2045: a systematic analysis for the global burden of disease study 2021.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1561568},
pmid = {40612577},
issn = {2296-858X},
abstract = {BACKGROUND: Blindness and vision loss (BVL) is a major public health concern. Non-communicable diseases (NCDs), including cataract, glaucoma, age-related macular degeneration, diabetic retinopathy and etc., were the leading causes of vision impairment globally.<br><br>METHODS: We extracted global, regional, national, age-and sex-specific data on the prevalence and years lived with disability (YLDs) of BVL caused by NCDs from the Global Burden of Disease Study 2021 (GBD 2021), and then conducted a secondary comparative analysis based on time, location, age, gender, socioeconomic development index (SDI) and health system level.<br><br>RESULTS: From 1990 to 2021, the global incidence of BVL caused by NCDs continuously increased. In 2021, 1475648.6 thousand BVL cases caused by NCDs occurred globally, and ASR of YLDs reached 371.1 per 100,000 population. Great disparities were found across different genders, ages, and locations. Higher burdens were noted among females, older adult individuals, regions with lower SDI or less advanced health systems.<br><br>CONCLUSION: The burden of BVLs caused by NCDs has increased significantly since 1990 and varies widely across regions. Greater efforts are needed in NCDs control and vision protection, especially in older adult individuals and females, in regions with lower SDI, and in regions with less advanced health systems.},
}
@article {pmid40611130,
year = {2025},
author = {Sekulic, A and Herr, SM and Mulfaul, K and Pompös, IM and Winkler, S and Dietrich, C and Obermayer, B and Mullins, RF and Conrad, T and Zipfel, PF and Sennlaub, F and Skerka, C and Strauß, O},
title = {Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration.},
journal = {Journal of neuroinflammation},
volume = {22},
number = {1},
pages = {173},
pmid = {40611130},
issn = {1742-2094},
mesh = {Animals ; *Macular Degeneration/metabolism/pathology/genetics ; Humans ; Mice ; Retinal Pigment Epithelium/metabolism/pathology ; *Inflammation/metabolism/pathology/genetics ; Mice, Inbred C57BL ; *Complement C3b Inactivator Proteins/metabolism/genetics ; Mice, Knockout ; Disease Models, Animal ; Mice, Transgenic ; },
abstract = {Age-related macular degeneration (AMD), a multifactorial type of retinal degeneration represents the most common cause for blindness in elderly. Polymorphisms in complement factor-H increase, while absence of factor-H-related protein-1 (FHR1) decreases the AMD risk, currently explained by their opposing relationship. Here we identify a FHR1-driven pathway fostering chronic cellular inflammation. FHR1 accumulates below the retinal pigment epithelium (RPE) in AMD donor tissue and similarly the murine homolog, muFHR1 is abundant in three AMD-relevant mouse models. These mouse models express the muFHR1 receptor EGF-like module-containing mucin-like hormone receptor 1 (Emr1) on the RPE and on invading mononuclear phagocytes (MP), where both cells form clusters via muFHR1/Emr1. FHR1 ignited EMR2-dependent Ca[2+]-signals and gene expression in both human RPE cell line and in vivo where muFHR1 affects Emr1[+] cells (RPE and MP) gene expression shown by RNAseq analysis. As muFHR1 deletion in mice revealed significantly reduced MP invasion and neoangiogenesis in laser-induced choroidal neovascularization, we hypothesize that FHR1 accumulates, stabilizes and activates MP in the stage of RPE degeneration.},
}
@article {pmid40610046,
year = {2025},
author = {Xu, P and Chotcomwongse, P and Zhang, W and Chen, X and Wu, X and Chung, FHT and Zhang, X and He, M and Shi, D and Ruamviboonsuk, P},
title = {AngioReport: dataset and baseline methods for fundus angiography report generation.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {11},
pages = {1283-1288},
doi = {10.1136/bjo-2024-327006},
pmid = {40610046},
issn = {1468-2079},
mesh = {Humans ; *Fluorescein Angiography/methods ; Retrospective Studies ; Female ; Male ; Fundus Oculi ; Middle Aged ; Aged ; Indocyanine Green/administration &amp; dosage ; Adult ; Aged, 80 and over ; Coloring Agents/administration &amp; dosage ; },
abstract = {PURPOSE: To develop an annotated fundus angiographic dataset, including fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA), and establish baseline methods for automatic report generation.<br><br>METHODS: This retrospective study reviewed patients aged &#x2265;18 years who underwent FFA or ICGA at Rajavithi Hospital, Thailand, between 1 January and 31 December 2019. A total of 55&#x2009;361 de-identified images from 1691 patients (3179 eyes) were annotated by retinal specialists with detailed descriptions of the type, location, shape, size and pattern of abnormal fluorescence. Two baseline methods were developed: (1) a classification-based approach using ResNet101 with class-specific residual attention for multi-label lesion recognition and (2) a language-generation approach using the Bootstrapping Language-Image Pre-training framework, fine-tuned on angiographic images and structured reports. Model performances were evaluated using F1 score and BERTScore.<br><br>RESULTS: The dataset includes 24 diagnostic conditions, with macular neovascularisation (32.5%) being the most prevalent, followed by unremarkable findings (21.8%) and dry age-related macular degeneration (10.2%). Most eyes (81.8%) underwent both FFA and ICGA. Hyperfluorescence was observed in 75.6% of cases, predominantly due to leakage, while hypofluorescence was present in 28.1%. The classification-based method achieved an average score of 7.966, demonstrating superior performance in recognising choroidal neovascularisation, hyperfluorescent and hypofluorescent areas. The language-generation method achieved a comparable average score of 7.947, excelling in impression recognition and the hyperfluorescence identification.<br><br>CONCLUSION: We present the largest annotated fundus angiographic dataset to date, along with two effective baseline methods for automatic report generation, offering a valuable foundation for advancing artificial intelligence applications in ophthalmology.},
}
@article {pmid40610024,
year = {2025},
author = {Trinh, M and Duong, A and Cheung, R and Chen, S and Ng, D and Friedrich, J and Hodge, C and Nivison-Smith, L and Ly, A},
title = {Proposal of a Simpler Eye-Level Risk Model Incorporating Reticular Pseudodrusen for the Clinical Prediction of Late Age-Related Macular Degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {8},
pages = {936-945},
pmid = {40610024},
issn = {1442-9071},
support = {//Future Vision Foundation/ ; },
mesh = {Humans ; Retrospective Studies ; *Retinal Drusen/diagnosis ; Female ; Male ; Aged ; Prognosis ; Disease Progression ; Risk Assessment/methods ; Aged, 80 and over ; Risk Factors ; *Macular Degeneration/diagnosis ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Middle Aged ; Fluorescein Angiography ; Visual Acuity ; },
abstract = {BACKGROUND: The updated simplified AREDS risk model predicts progression to late age-related macular degeneration (AMD) by person, describing up to nine observations across both eyes and 10 annual risk scores (0-4, with/without reticular pseudodrusen [RPD]). This study proposes an abridged model to enable inter-eye comparisons and potentially enhance clinical efficiency.<br><br>METHODS: This retrospective cohort study included 269 participants with early/intermediate AMD over 7&#x2009;years. The full, person-level updated simplified AREDS risk model was compared to eye-level candidate risk models, derived by removing the least predictive biomarkers. The main outcomes were prognostic performance (AUC) and risk score separability (&#x3c7; [2]).<br><br>RESULTS: At 1-3&#x2009;years, the full model showed prognostic performance (AUC&#x2009;&#xb1;&#x2009;SE) up to 84.52%&#x2009;&#xb1;&#x2009;5.93%, with overlap between most risk scores (&#x3c7; [2]&#x2009;&#x2264;&#x2009;2.08). Removing large drusen and pigmentary abnormalities in the fellow eye, intermediate drusen in both eyes, and redefining RPD presence as eye-specific maintained prognostic performance (up to 84.71%&#x2009;&#xb1;&#x2009;4.72%). Assigning one point per retained biomarker, based on similar adjusted risks, improved risk score separability (&#x3c7; [2]&#x2009;&#x2265;&#x2009;3.85, p&#x2009;<&#x2009;0.05) while reducing the number of annual scores from 10 to five.<br><br>CONCLUSIONS: The updated simplified AREDS risk model can be essentially halved without compromising prognostic performance by deriving eye-specific biomarkers and assigning one point per biomarker (large drusen, pigmentary abnormalities, and RPD in the primary eye, and late AMD in the fellow eye). This eye-level risk stratification may improve clinical efficiency and inter-eye study designs when one eye is of particular interest. An example of 3-year risks (scores 0-4) was &#x2248;4%, 8%, 16%, 32%, and 64%.},
}
@article {pmid40609554,
year = {2025},
author = {Pan, H and Miao, J and Yu, J and Li, J and Wang, X and Feng, J},
title = {Multi-modal classification of retinal disease based on convolutional neural network.},
journal = {Biomedical physics &amp; engineering express},
volume = {11},
number = {4},
pages = {},
doi = {10.1088/2057-1976/adeb92},
pmid = {40609554},
issn = {2057-1976},
mesh = {Humans ; Algorithms ; *Convolutional Neural Networks ; Deep Learning ; Diabetic Retinopathy/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging ; *Multimodal Imaging ; Neural Networks, Computer ; Retina/diagnostic imaging ; *Retinal Diseases/diagnostic imaging/classification ; *Tomography, Optical Coherence/methods ; },
abstract = {Retinal diseases such as age-related macular degeneration and diabetic retinopathy will lead to irreversible blindness without timely diagnosis and treatment. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images provide complementary views of the retina, and the integration of the two imaging modalities can improve the accuracy of retinal disease classification. We propose a multi-modal classification model consisting of two branches to automatically diagnose retinal diseases, in which OCT and OCTA images are efficiently integrated to improve both the accuracy and efficiency of disease diagnosis. A bright line cropping is used to remove the useless black edge region while preserving the lesion features and reducing the calculation load. To solve the insufficient data issue, data enhancement and loose matching methods are adopted to increase the data amount. A two-step training method is used to train our proposed model, alleviating the limited training images. Our model is tested on an external test set instead of a training set, making the classification results more rigorous. The intermediate fusion and two-step training methods are adopted in our multiple classification model, achieving 0.9667, 0.9418, 0.8569, 0.9422, and 0.8921 in average accuracy, precision, recall, specificity, and F1-Score, respectively. Our multi-modal model outperforms the single-modal model, the early, and late fusion multi-modal model in accuracy. Our model offers doctors less human error, lower cost, more uniform, and effective mass screening, thus providing a solution to improve deep learning performance in terms of a relatively fewer number of training data and even more imbalanced classes.},
}
@article {pmid40609263,
year = {2025},
author = {Yanagi, Y and Ichikawa, H and Nguyen, LBT and Hayashi, A and Abe, N and Abe, H and Uchida, S},
title = {mRNA vaccination mitigates pathological retinochoroidal neovascularization in animal models.},
journal = {Vaccine},
volume = {61},
number = {},
pages = {127451},
doi = {10.1016/j.vaccine.2025.127451},
pmid = {40609263},
issn = {1873-2518},
mesh = {Animals ; Disease Models, Animal ; *RNA, Messenger/immunology/administration &amp; dosage/genetics ; Mice, Knockout ; Mice ; *Choroidal Neovascularization/prevention &amp; control ; Mice, Inbred C57BL ; *Vaccination/methods ; Receptors, LDL/genetics ; *Retinal Neovascularization/prevention &amp; control ; Female ; },
abstract = {Retinochoroidal neovascularization (NV), involved in macular degeneration, diabetic retinopathy, and other ocular diseases, causes vision impairment and blindness. Current treatments rely on repeated intraocular injections of anti-angiogenic drugs, which are burdensome for patients and clinicians, and some patients fail to respond to the treatments. This study investigates the potential of mRNA vaccination to mitigate NV and treat ocular pathologies. The vaccine targets leucine-rich alpha-2-glycoprotein 1 (LRG1), a protein specifically expressed in pathological neovascularization, inducing anti-LRG1 antibody responses in mice. In a laser-induced NV model, the LRG1 mRNA vaccine reduces NV area and leakage while inhibiting microglial cell infiltration. Histological analysis shows no adverse effects on retinal architecture or glial cell activation. Additionally, in Vldlr knockout mice, LRG1 mRNA administration suppresses ongoing neovascularization and downregulates key angiogenic mediators. These findings highlight the therapeutic potential of LRG1 mRNA as a novel strategy for CNV-associated diseases.},
}
@article {pmid40608264,
year = {2025},
author = {Khodor, A and Caranfa, JT and Nanda, T and Ruiz-Lozano, RE and Quiroga-Garza, ME and Choi, S and Chehab, A and Ramos-Dávila, EM and Heier, JS and Shah, CP and Witkin, AJ},
title = {Functional and Anatomical Outcomes of Faricimab in Previously Treated Wet Age-Related Macular Degeneration: Systematic Review and Pooled Analysis.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {8},
pages = {1965-1984},
pmid = {40608264},
issn = {2193-8245},
abstract = {INTRODUCTION: To evaluate the outcomes of intravitreal faricimab (IVF; Vabysmo[®]) in previously treated patients with wet age-related macular degeneration (wAMD), focusing on best available visual acuity (BAVA), central subfield thickness (CST), injection interval, complications, fluid resolution, and reversion rates to prior therapies.<br><br>METHODS: The PubMed, Embase, and Google Scholar databases were searched for studies reporting outcomes of treatments for previously treated cases of wAMD. Mean differences (MD) with 95% confidence intervals (CI) were used to compute the effect size of the change in outcomes.<br><br>RESULTS: A total of 29 studies with 2070 patients (1003 women, mean age 78.9&#xa0;years) and 2128 eyes were included. BAVA and CST were reported in 28 studies, fluid status in 21, injection interval in 14, and reversion rates in 6. Pooled analysis showed significant but modest improvement in BAVA when IVF was given for&#x2009;>&#x2009;6&#xa0;months (MD&#x2009;= -0.026 LogMAR, p&#x2009;<&#x2009;0.05) but not at earlier follow-ups. A similar trend was noted with injection interval extension when IVF was given beyond 6&#xa0;months (MD&#x2009;= +2.1&#xa0;weeks, p&#x2009;<&#x2009;0.05). CST reduction was observed at all time points (overall MD&#x2009;= -37.7&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.05). Complication rates were reported in nine studies, with an overall rate of 1.2%, including retinal pigment epithelium tear, intraocular inflammation, endophthalmitis, and subretinal hemorrhage. Reversion to prior or other anti-vascular endothelial growth factor (anti-VEGF) therapy was reported in six studies, occurring in 23% of eyes.<br><br>CONCLUSIONS: We reported the outcomes of utilizing IVF in previously treated cases of wAMD. IVF showed a significant improvement in CST at all time points and in the extension of injection interval. Visual outcomes remained unchanged when followed for less than 6&#xa0;months but improved significantly but modestly when followed for more than 6&#xa0;months. Switching to intravitreal faricimab may be a useful treatment option for previously treated patients with wAMD, with a goal of reducing treatment burden and improving treatment efficacy.},
}
@article {pmid40608114,
year = {2025},
author = {Brown, HDH and Vernon, RJW and Baseler, HA and Morland, AB},
title = {Reduced functional connectivity between central representations of V1 and foveal-biased face-selective region in central vision loss.},
journal = {Brain structure &amp; function},
volume = {230},
number = {6},
pages = {111},
pmid = {40608114},
issn = {1863-2661},
support = {1523/1524//Fight for Sight UK/ ; },
mesh = {Humans ; Male ; Female ; Magnetic Resonance Imaging ; *Visual Cortex/physiopathology/diagnostic imaging ; Middle Aged ; Aged ; *Fovea Centralis/physiopathology ; *Visual Pathways/physiopathology/diagnostic imaging ; Brain Mapping ; Visual Fields/physiology ; *Macular Degeneration/physiopathology/diagnostic imaging ; Adult ; Pilot Projects ; *Facial Recognition/physiology ; },
abstract = {Individuals with central visual deficits exhibit atrophy of the visual cortex in regions representing the central visual field and show little or no functional response there. Information in the central and peripheral visual field appear to be represented preferentially in extrastriate regions that are selective to faces and places, respectively. We recruited individuals with bilateral macular degeneration (age-related or juvenile) and age-matched sighted controls. We used resting state fMRI (RS-fMRI) to examine functional connectivity between striate (V1) and extrastriate face and place selective areas as it allows better comparison between those with unaffected vision and those with visual loss, whose stimulus related signals are already known to differ from those of controls. Selective deficits emerged in our central loss group, showing reduced functional connectivity between regions with foveal biases (central V1-face area) compared to sighted controls, whereas no such difference emerged in the peripheral biased regions (peripheral V1-place area). This result was evident regardless of whether eyes were closed or open and fixating, but was only significant in the right hemisphere, supporting the functional lateralisation of face processing. This pilot study provides some evidence for reduced functional connectivity between foveal-biased visual areas in central vision loss, suggesting that communication within the posterior visual pathway may be selectively affected in partial vision loss. Functional connectivity differences did not appear to be driven by changes in viewing condition. RS-fMRI is a valuable tool that allows us to explore functional brain changes without the need for retinal input.},
}
@article {pmid40608095,
year = {2025},
author = {Liu, JY and Cheng, CK and Bai, CH and Chiu, CY},
title = {Long-term remission and incidence of recurrence of neovascularization in intravitreal injection treated exudative age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {9},
pages = {2541-2550},
pmid = {40608095},
issn = {1435-702X},
mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/epidemiology ; Recurrence ; Incidence ; Tomography, Optical Coherence/methods ; *Visual Acuity ; Follow-Up Studies ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Time Factors ; Fundus Oculi ; Taiwan/epidemiology ; Remission Induction ; Aged, 80 and over ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; *Macula Lutea/pathology ; },
abstract = {PURPOSE: This study evaluates the long-term remission (LTR) rate, recurrence rate, and prognostic factors of extended remission and recurrence in macular neovascularization (MNV) eyes treated with aflibercept.<br><br>METHODS: This was a retrospective cohort of treatment-na&#xef;ve MNV eyes treated in Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan with intravitreal aflibercept between 2015 and 2023. Patients followed pro re nata (PRN) or Treat-and-Extend (T&amp;E) protocols. Long-term remission (LTR) was defined as over 6 months of disease inactivity without injection. Binary logistic regression and Cox proportional hazard regression assessed associations with LTR and time to recurrence.<br><br>RESULTS: Of 144 eyes, 68.75% achieved LTR after an average of 21.32 months after treatment, with no difference between PRN and T&amp;E groups. Among LTR cases, 69.7% experienced recurrence after a median 15 months (range: 6&#x2009;~&#x2009;67). Firth multinomial logistic regression found younger age [OR, 0.898 (0.836 to 0.946; p&#x2009;=&#x2009;0.032)], fewer injections per year [OR, 0 (0.000 to 0.001; p&#x2009;=&#x2009;0.004)], polypoid choroidal vasculopathy (PCV) [OR, 6.170 (1.811 to 21.039; p&#x2009;=&#x2009;0.033)], and retinal angiomatous proliferation (RAP) [OR, 24 450.658 (24 450.657 to 24 450.658; p&#x2009;<&#x2009;0.001)] associated with LTR. Cox regression showed more yearly injections [HR, 7.621(0.376 to 0.972; p&#x2009;=&#x2009;0.038)] led to earlier recurrence, while baseline subretinal fluid (SRF) [HR, 0.604 (0.376 to 0.972; p&#x2009;=&#x2009;0.038)] delayed recurrence.<br><br>CONCLUSION: Implementing our exit strategies, 68.75% of eyes achieved LTR across the two injection protocols. Age, disease subtype, baseline anatomical features, and yearly injection numbers may predict sustained remission and a longer time to experience recurrence.},
}
@article {pmid40606666,
year = {2025},
author = {Luo, Q and Huang, J and Shi, L and Zhang, G and Xue, L and Wu, K and Li, X and Yang, L and Li, D and Mao, L and Luo, J},
title = {Identification and functional characterization of ABCA4 gene variants in three patients with Stargardt disease or retinitis pigmentosa.},
journal = {Frontiers in genetics},
volume = {16},
number = {},
pages = {1516872},
pmid = {40606666},
issn = {1664-8021},
abstract = {INTRODUCTION: The diversity of phenotypes, ranging from inherited retinal dystrophies (such as Stargardt disease 1, cone-rod dystrophy 3, and retinitis pigmentosa 19) to late-onset age-related macular degeneration 2, has been attributed to loss-of-function variants in the ABCA4 gene. In this study, we aimed to identify and analyze potential pathogenic ABCA4 variants in patients with Stargardt disease or retinitis pigmentosa and to explore the impact of an intronic variant (NM_000350.3:c.6386 + 4A>G) on mRNA splicing.<br><br>METHODS: We enrolled three patients from unrelated families with Stargardt disease or retinitis pigmentosa after comprehensive ophthalmological evaluations were performed. Whole-exome sequencing and Sanger sequencing were applied for mutation screening, focusing on inherited retinal dystrophy-related genes. Additionally, the splicing alteration caused by c.6386 + 4A>G was functionally characterized by a minigene splicing assay.<br><br>RESULTS: Five ABCA4 germline variants were detected in three patients: one frameshift, one nonsense, one splicing, and two missense variants. Furthermore, two pathogenic and two likely pathogenic variants and one variant of uncertain significance were determined according to ACMG/AMP and ClinGen sequence variant interpretation (SVI) guidelines. The minigene splicing assay result proved that c.6386 + 4A>G affected the wild-type donor splice-site recognition of intron 46 and yielded a truncated transcript with a 47-bp deletion in exon 46.<br><br>DISCUSSION: Our study identified two novel ABCA4 variants, expanding the mutational spectrum of the ABCA4 gene in Stargardt disease and retinitis pigmentosa while providing new insights into the molecular pathology of ABCA4 splicing defects.},
}
@article {pmid40601621,
year = {2025},
author = {Anderer, S},
title = {GLP-1 Drugs Linked to Higher Risk of Age-Related Macular Degeneration.},
journal = {JAMA},
volume = {334},
number = {5},
pages = {383},
doi = {10.1001/jama.2025.10318},
pmid = {40601621},
issn = {1538-3598},
}
@article {pmid40601523,
year = {2025},
author = {Choe, BS and C, A and Mk, P and Kim, J and Baek, KS and Park, YK},
title = {Enhanced Oral Bioavailability of Lutein and Zeaxanthin via a Self-Emulsifying Delivery System: A Randomized, Double-Blind Cross-Over Study.},
journal = {Journal of medicinal food},
volume = {28},
number = {8},
pages = {824-832},
doi = {10.1089/jmf.2025.k.0060},
pmid = {40601523},
issn = {1557-7600},
mesh = {Humans ; *Lutein/pharmacokinetics/blood/administration &amp; dosage ; Male ; *Zeaxanthins/pharmacokinetics/blood/administration &amp; dosage ; Double-Blind Method ; Cross-Over Studies ; Biological Availability ; Adult ; *Dietary Supplements/analysis ; Young Adult ; Administration, Oral ; Emulsions/chemistry ; *Drug Delivery Systems ; },
abstract = {This study was conducted to evaluate and verify the improved bioavailability, as determined by the plasma concentrations of lutein and zeaxanthin, of the test supplement, XanMax® 2002 plus LuZeAbility™, as compared to the reference supplement, XanMax® 2002. For this purpose, this study was designed as a randomized, double-blind, two-group, two-period cross-over clinical trial research. A total of 24 male subjects participated in the clinical trial. They were randomized 1:1 into group 1 or 2 to consume two types of supplements in two separate periods. This study aimed to propose and demonstrate that the bioavailability and the plasma concentrations of lutein and zeaxanthin in the test supplement were significantly higher (110-132.8%) than in the reference supplement in all consecutive periods, such as 12 to 72 h after intake and at the time of maximum concentration. These results are expected to strengthen macular pigment optical density levels, ultimately providing a safe and effective intervention for comprehensively promoting eye health. Therefore, the findings of this study have significant pharmacokinetic implications and offer valid theoretical and practical insights for both academic research and the industrial development in the supplement market.},
}
@article {pmid40601515,
year = {2025},
author = {Harris, J and Wu, D},
title = {The Role of Inflammation in Age-Related Macular Degeneration.},
journal = {International ophthalmology clinics},
volume = {65},
number = {3},
pages = {82-113},
pmid = {40601515},
issn = {1536-9617},
support = {//Gragoudas-Folkman Research Award/ ; },
mesh = {Humans ; *Inflammation/complications ; *Macular Degeneration/etiology ; },
abstract = {Age-related macular degeneration (AMD) is a common neurodegenerative disease that results in significant morbidity and economic cost to patients and society. While advances in our understanding of the mechanisms of neovascularization have led to breakthrough vision-saving treatments for "wet" AMD, the "dry" variant of AMD, geographic atrophy, still poses significant clinical and scientific challenges. Many genetic and environmental factors have been linked with AMD, providing clues for understanding the disease mechanisms driving "dry" AMD. Evidence of neuroinflammation has been found across a wide spectrum of neurodegenerative diseases including AMD and therapies targeting inflammation, including recent complement inhibitors, have been investigated as treatments for "dry" AMD. Here we survey the evidence from human patients of the potential role of inflammation in AMD and review the efforts to treat AMD with therapeutic interventions targeting mediators of inflammation.},
}
@article {pmid40601512,
year = {2025},
author = {Bagheri, S and Ntentakis, DP and Emfietzoglou, M and Ashourizadeh, H and Grinspan, N and Ploumi, I and Armstrong, GW and Miller, JB},
title = {Sterile Intraocular Inflammation Following Intravitreal Injections: Pathogenesis, Clinical Features, and Management.},
journal = {International ophthalmology clinics},
volume = {65},
number = {3},
pages = {63-70},
pmid = {40601512},
issn = {1536-9617},
mesh = {Humans ; *Intravitreal Injections/adverse effects ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; *Endophthalmitis/diagnosis/etiology/therapy/chemically induced ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Vasculitis/chemically induced/diagnosis ; },
abstract = {Intravitreal injections have revolutionized the treatment of retinal diseases, yet there are possible complications, such as noninfectious intraocular inflammation, a complication that may threaten vision and mimic infectious endophthalmitis. This review synthesizes current knowledge on inflammation after intravitreal therapy, with particular focus on sterile intraocular inflammation and retinal vasculitis associated with anti-VEGF agents such as brolucizumab and newer complement inhibitors like pegcetacoplan. The pathogenesis is multifactorial, involving patient-specific immune responses, drug-specific properties including aggregation or impurities, and deviations in preparation or delivery techniques. Clinical presentations range from anterior uveitis and vitritis to occlusive retinal vasculitis. Visual outcomes vary and depend on prompt recognition and appropriate management. Epidemiologic data show variable incidence across agents, with brolucizumab demonstrating higher rates of inflammation compared with ranibizumab or aflibercept. Treatment includes corticosteroids and discontinuation of the offending agent, with rare cases requiring surgical intervention. As the therapeutic landscape expands, heightened awareness and standardized evaluation of postinjection inflammation are critical to improving safety and preserving vision.},
}
@article {pmid40601510,
year = {2025},
author = {Zhou, HW and Kim, LA},
title = {Gene Therapy in Age-related Macular Degeneration.},
journal = {International ophthalmology clinics},
volume = {65},
number = {3},
pages = {48-55},
doi = {10.1097/IIO.0000000000000567},
pmid = {40601510},
issn = {1536-9617},
mesh = {Humans ; *Genetic Therapy/methods ; *Macular Degeneration/therapy/genetics ; Genetic Vectors ; },
abstract = {Recent advances in gene therapy and salient features of the current AMD therapeutic landscape have led to increased interest in applying gene therapy approaches to AMD. This review will discuss approaches to drug administration, viral and non-viral delivery vectors, and current trials in gene therapy for both wet and dry AMD. Drug administration routes include subretinal, intravitreal, and suprachoroidal approaches. Viral vectors include adenoviral, lentiviral, and adeno-associated viral (AAV) vectors. Non-viral vectors include lipid nanoparticle (LNP) and polymer-based vectors. Current trials in wet AMD include ADVM-022 and RGX-314. Current trials in dry AMD include GT-005 and JNJ-1887.},
}
@article {pmid40599631,
year = {2025},
author = {Villicana, J and Joseph, A and Goldstein, O and Luu, K and Matta, E and Ngo, D and Nakawaki, K and Siebein, K and Sustek, R and Tang, K and Shiraishi, M and Mayorga, A and Moon, SH and Rajagopal, S and Chauhan, RK and Soangra, R},
title = {THE ROLE OF PERIPHERAL VISION IN ENHANCING BALANCE AND POSTURAL STABILITY: INSIGHTS FROM CENTRAL VISION OBSTRUCTION.},
journal = {Biomedical sciences instrumentation},
volume = {61},
number = {1},
pages = {1-8},
pmid = {40599631},
issn = {0067-8856},
support = {R15 HD110941/HD/NICHD NIH HHS/United States ; },
abstract = {This study examines the role of peripheral vision in maintaining postural stability, particularly when central vision is obstructed, using Sensory Organization Testing (SOT) with computer dynamic posturography. Ten participants (5 males, 5 females, aged 21-34 years) were tested under three conditions: full vision, full occlusion, and central vision obstruction allowing only peripheral vision access. Results revealed significantly better balance performance in the peripheral vision condition during somatosensory perturbations (Condition 4), with equilibrium scores higher than in the full vision condition (p = 0.02). Similarly, visual preference (VIS) scores, indicating reliance on visual input, were significantly elevated under peripheral vision conditions (p = 0.03). These findings highlight peripheral vision's critical role in improving postural sway and maintaining balance when central vision is impaired, as seen in conditions such as age-related macular degeneration (AMD). While central vision is vital for daily tasks requiring focused attention, peripheral vision provides crucial environmental cues for balance and stability. This research underscores the need for targeted interventions and balance training programs to mitigate fall risks in individuals with central vision loss. Future studies will explore these effects in populations with visual impairments to enhance clinical relevance and applicability of central vision on balance.},
}
@article {pmid40598116,
year = {2025},
author = {Yufeng, X and Ningxi, H and Mingzhi, S and Weixin, Z and Panpan, Y},
title = {Real-world outcomes of a loading phase with intravitreal faricimab in refractory Neovascular Age-Related Macular Degeneration (nAMD) patients.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {347},
pmid = {40598116},
issn = {1471-2415},
support = {LTGY24H120002//Zhejiang Provincial Natural Science Foundation of China/ ; 2025-KYY-518052-0055//Chen Jumei Foundation/ ; },
mesh = {Humans ; Intravitreal Injections ; Male ; Female ; *Visual Acuity ; Aged ; Prospective Studies ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged, 80 and over ; Follow-Up Studies ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Fluorescein Angiography ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: Intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents is the standard of care for neovascular age-related macular degeneration (nAMD), but treatment resistance and incomplete fluid resolution remain challenges in refractory cases. This study investigates the real-world outcomes of faricimab in patients with previously treated refractory nAMD.<br><br>METHODS: A prospective single center study was conducted involving patients with refractory nAMD treated with a loading dose of 3 IVI of faricimab 6 mg/0.05 ml, administered every four weeks. All patients included in this study had previously received a minimum of 3 consecutive intravitreal injections of other anti-VEGF. Main outcome measures included best-corrected visual acuity (BCVA) and OCT outcomes at follow-up time for 3 months.<br><br>RESULTS: Thirty-five eyes of 35 patients were included. The BCVA (logMAR) improved from 0.84&#xb1;0.49 to 0.76&#xb1;0.49 at 3 months (P = 0.025). The central macular thickness (CMT) decreased significantly from 447.65&#xb1;161.46 &#xb5;m to 327.33&#xb1;147.78 &#xb5;m at 3 months (P < 0.001). The correlation analysis revealed that age and ellipsoid zone (EZ) discontinuity exhibited a weak positive correlation with the final BCVA (P < 0.05). Baseline BCVA demonstrated a strong positive correlation with the final BCVA (P < 0.05). Meanwhile, baseline CMT, intraretinal fluid (IRF), scar, and subretinal hyperreflective material (SHRM) showed a moderate positive correlation with the final BCVA (P < 0.05). Multivariate logistic regression analysis demonstrated that baseline BCVA (P = 0.032) and age (P = 0.047) were independent predictors of final BCVA.<br><br>CONCLUSION: In the short term, faricimab led to significant improvements in BCVA and CMT, as well as reductions in retinal fluid, making it an effective treatment option for previously treated refractory nAMD with minimal adverse effects. Limitations include the single-arm design, small sample size, and lack of long-term durability assessment.},
}
@article {pmid40597158,
year = {2025},
author = {Yang, Y and Chen, L and Liu, Q and Mu, M and Huang, J and Zhang, G and Song, Q},
title = {Long-term exposure to multiple air pollutants and multi-level socioeconomic status: joint effects on age-related macular degeneration, subsequent ocular comorbidity, and death in middle-aged and older adults.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {354},
pmid = {40597158},
issn = {1741-7015},
support = {2021QNRC001//China Association for Science and Technology/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology/mortality ; Male ; Aged ; Female ; Middle Aged ; *Air Pollutants/adverse effects ; *Air Pollution/adverse effects ; *Social Class ; Comorbidity ; *Environmental Exposure/adverse effects ; Life Expectancy ; United Kingdom/epidemiology ; Aged, 80 and over ; Incidence ; },
abstract = {BACKGROUND: Both air pollution and socioeconomic status (SES) are recognized as significant determinants of health outcomes. However, no study has explored the combined effects of air pollutants and SES on (1) age-related macular degeneration (AMD) incidence; (2) trajectories from baseline to AMD, subsequent ocular comorbidity (OCMD), and mortality; and (3) life expectancy in middle-aged and older adults.<br><br>METHODS: Using UK Biobank data, we created two composite air pollution scores (APS) and assessed SES at individual and neighborhood levels. OCMD was defined as glaucoma or cataract occurrence after AMD diagnosis. Cox proportional hazard regression models, multistate models, and life tables were used to assess associations and calculate life expectancy.<br><br>RESULTS: Over a median of 12.5 years, 3859 participants developed AMD, 2907 participants developed OCMD, and 23,363 died. Compared to those with low APS and favorable SES, individuals with high APS and unfavorable SES had highest risk (APS1: individual-level SES HR 1.41, 95% CI: 1.18-1.67, area-level SES HR 1.31, 95% CI: 1.15-1.49; APS2: individual-level SES HR 1.51, 95% CI: 1.27-1.80; area-level SES HR 1.31, 95% CI: 1.15-1.49), after adjusting for all potential covariates. Among five transitions, the combined effects were significant in transitions from baseline to incident AMD, from AMD to OCMD, and from baseline to death. Significant life expectancy disparities were observed; individuals with low individual-level SES had shortest life expectancies across APS tertiles, with similar but less pronounced effects for area-level SES.<br><br>CONCLUSIONS: Our study underscores the need for interventions addressing air pollution and SES to reduce AMD risk, improve ocular health, and enhance life expectancy in aging populations.},
}
@article {pmid40597124,
year = {2025},
author = {Erkan, E and Bayhan, SA and Bayhan, HA},
title = {Evaluation of the effects of phacoemulsification surgery in patients with wet age-related macular degeneration using optical coherence tomography angiography.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {354},
pmid = {40597124},
issn = {1471-2415},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Phacoemulsification/methods ; Male ; Female ; Prospective Studies ; Aged ; *Wet Macular Degeneration/surgery/complications/diagnosis/physiopathology ; *Fluorescein Angiography/methods ; Visual Acuity/physiology ; Aged, 80 and over ; Choroidal Neovascularization ; Follow-Up Studies ; Choroid/blood supply ; *Cataract/complications ; Middle Aged ; Fundus Oculi ; },
abstract = {PURPOSE: To assess the impact of uncomplicated phacoemulsification surgery in patients with wet age-related macular degeneration (AMD) using optical coherence tomography-angiography (OCTA).<br><br>DESIGN: Prospective study.<br><br>METHOD: The study included eyes from 44 patients diagnosed with AMD who underwent phacoemulsification surgery and 44 eyes from 44 patients without an indication for cataract surgery. Patients who had received anti-vascular endothelial growth factor therapy within the last six months were excluded. Best-corrected visual acuity measurements, optical coherence tomography, and OCTA were performed preoperatively and at postoperative months 1, 3, and 6. During the same sessions, choroidal neovascular membrane area was evaluated manually with OCTA.<br><br>RESULTS: Throughout follow-up, no significant differences were observed between the surgical and control groups regarding membrane area (p&#x2009;>&#x2009;0.05). However, the change in membrane area in the surgical group, measured as an increase of 0.17&#x2009;&#xb1;&#x2009;0.14 mm[2], was statistically significant (p&#x2009;<&#x2009;0.05). No significant difference was found between the two groups in terms of flow area (p&#x2009;>&#x2009;0.05). Vessel density measurements in the superficial capillary plexus did not significantly differ between the groups (p&#x2009;>&#x2009;0.05). At the six-month visit, a significant decrease was observed in small-caliber vessels (p&#x2009;<&#x2009;0.05) within the surgical group, along with a significant increase in the perilesional halo (p&#x2009;<&#x2009;0.05); however, no significant changes were noted in other activation criteria (p&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: Phacoemulsification was determined to induce changes in certain parameters of the choroidal neovascularization in patients with wet AMD. Therefore, the timing of surgical intervention should be carefully planned, considering patients' daily life activities.},
}
@article {pmid40596765,
year = {2025},
author = {Kim, J and Han, LS and Robinson, L and Young-Zvandasara, T},
title = {Randomised Controlled Trial: Influence of Subconjunctival Anaesthesia Duration on Pain Perception During Intravitreal Injections.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {8},
pages = {918-924},
doi = {10.1111/ceo.14579},
pmid = {40596765},
issn = {1442-9071},
mesh = {Humans ; *Intravitreal Injections ; Female ; Male ; *Anesthesia, Local/methods ; Pain Measurement ; *Anesthetics, Local/administration &amp; dosage ; Conjunctiva/drug effects ; *Lidocaine/administration &amp; dosage ; Single-Blind Method ; Aged ; Middle Aged ; *Pain Perception/physiology ; Time Factors ; *Eye Pain/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; *Pain, Procedural ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; },
abstract = {BACKGROUND: The intravitreal injection (IVI) is one of the most performed vitreoretinal procedures in ophthalmology. Subconjunctival anaesthesia (SCA) with 2% lidocaine is a commonly used modality to reduce procedural pain and patient distress. Currently, there is no unifying recommended wait time between SCA and IVI. The purpose of this study is to determine the optimal wait time between the two, whilst maintaining clinical efficiency.<br><br>METHODS: Single-blinded randomised clinical trial. Two hundred and forty patients were randomly assigned to one of four groups: wait time of 2, 3, 4 or 5&#x2009;min. The primary outcome was pain level graded by the patient on a 10-point visual analogue scale. The secondary outcome was the willingness to receive further IVI with the current pain level. Data points were collected on patient demographics and characteristics.<br><br>RESULTS: The mean pain scores showed a decreasing trend with increasing wait times, 2.27 (2&#x2009;min), 1.03 (3&#x2009;min), 0.67 (4&#x2009;min) and 0.58 (5&#x2009;min). More patients were willing to receive further IVI with increasing wait times, 92% (2&#x2009;min), 97% (3 and 4&#x2009;min), and 100% (5&#x2009;min). These differences were statistically significant at each time interval.<br><br>CONCLUSION: Longer wait times post-SCA were associated with better anaesthetic effect and higher patient acceptance to continue receiving IVI. The most marked difference was observed between 2- and 3-min groups. Based on our findings, a minimum wait time of 3&#x2009;min should be recommended as the group had reported acceptably low pain scores (1.03) while maintaining high patient satisfaction (97%).},
}
@article {pmid40594270,
year = {2025},
author = {Davari, A and Piroozkhah, M and Iranpour, A and Nejadghaderi, SA},
title = {The burden of age-related macular degeneration and its socioeconomic associates in the Eastern Mediterranean Region from 1990 to 2021.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {21950},
pmid = {40594270},
issn = {2045-2322},
support = {403000696//Kerman University of Medical Sciences/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology ; Female ; Male ; Aged ; Prevalence ; Mediterranean Region/epidemiology ; Middle Aged ; Aged, 80 and over ; Global Burden of Disease ; Socioeconomic Factors ; *Cost of Illness ; Adult ; },
abstract = {This research aimed to assess the trends in the burden of age-related macular degeneration (AMD) in the Eastern Mediterranean Region (EMR) by age, sex, socio-demographic index (SDI), and location. We extracted data on the prevalence and years lived with disability (YLDs) of AMD from the Global Burden of Disease (GBD) study 2021. The data included all 22 countries in the EMR from 1990 to 2021. Estimates were presented as counts, age-standardized rates per 100,000, and their corresponding 95% uncertainty intervals (UIs). In 2021, the EMR had an age-standardized point prevalence for AMD of 196.8 (95% UI: 161.5 to 240.2) and a YLD rate of 14.9 (10.3 to 20.5) per 100,000 individuals, which represents a decline of 8.1% (from - 11.1% to -5.0%) and 13.3% (from - 16.7% to -9.7%), respectively, when compared to the data from 1990. In 2021, Iran exhibited the highest age-standardized YLD rate at 25.0 (17.2 to 34.9), while Somalia recorded the lowest rate at 8.0 (5.2 to 11.8). Notably, all countries within the EMR demonstrated a reduction in their age-standardized YLD rates from 1990 to 2021, except Yemen. We found an M-shaped relationship between AMD burden and the SDI during 1990-2021. The burden initially increased until reaching an SDI of 0.3, followed by a decline to 0.4, then rose again, peaking at an SDI of 0.6, before showing a final descending trend at SDI values. Despite a reduction in the burden of AMD over the past thirty years, its prevalence continues to be remarkable. Our findings revealed that women experienced a greater burden of AMD than men in the EMR. Additionally, this study highlighted a reduction in age-standardized prevalence and YLD rates. These insights can serve as a foundational basis for developing policies aimed at preventing and treating AMD.},
}
@article {pmid40593839,
year = {2025},
author = {Reeve, MP and Loomis, S and Nissilä, E and Soare, TW and Rausch, T and Zheng, Z and Della Briotta Parolo, P and Ben-Isvy, D and Aho, E and Cesetti, E and Okunuki, Y and McLaughlin, H and Mäkelä, J and , and Kurki, M and Talkowski, ME and Korbel, JO and Connor, K and Meri, S and Daly, MJ and Runz, H},
title = {Loss of CFHR5 function reduces the risk for age-related macular degeneration.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5766},
pmid = {40593839},
issn = {2041-1723},
support = {R01 MH115957/MH/NIMH NIH HHS/United States ; R56 MH115957/MH/NIMH NIH HHS/United States ; U24 HG011450/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/genetics ; Aged ; Male ; Female ; Complement Factor H/genetics ; Genetic Predisposition to Disease ; Haplotypes ; Aged, 80 and over ; Complement Activation/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; *Complement C3b Inactivator Proteins/genetics ; Frameshift Mutation ; Case-Control Studies ; Retina/pathology ; Mutation, Missense ; Complement System Proteins ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent cause of vision loss in the elderly with limited therapeutic options. A single chromosomal region around the complement factor H gene (CFH) is reported to explain nearly 25% of genetic AMD risk. Here, we used association testing, statistical finemapping and conditional analyses in 12,495 AMD cases and 461,686 controls to deconvolute four major CFH haplotypes that convey protection from AMD. We show that beyond CFH, two of these are explained by Finn-enriched frameshift and missense variants in the CFH modulator CFHR5. We demonstrate through a FinnGen sample recall study that CFHR5 variant carriers exhibit dose-dependent reductions in serum levels of the CFHR5 gene product FHR-5 and two functionally related proteins at the locus. Genetic reduction in FHR-5 correlates with higher complement activation capacity and a thicker retinal photoreceptor layer. Our results propose therapeutic downregulation of FHR-5 as promising to prevent or treat AMD.},
}
@article {pmid40592385,
year = {2025},
author = {Wang, Z and Chen, L and Li, L and Wu, M and Zheng, B and Fan, Y},
title = {Aging reprograms the rhythmic transcriptome in the retina.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110504},
doi = {10.1016/j.exer.2025.110504},
pmid = {40592385},
issn = {1096-0007},
mesh = {Animals ; *Aging/physiology/genetics ; Mice, Inbred C57BL ; Mice ; *Circadian Rhythm/physiology/genetics ; *Transcriptome ; *Retina/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation/physiology ; },
abstract = {PURPOSE: Aging is a significant risk factor for various retinal degenerative diseases. However, its impact on diurnal transcriptional profile of the retina remains largely unexplored. Addressing this knowledge gap is crucial given the rising prevalence of age-related retinal diseases.<br><br>METHODS: We conducted high-throughput RNA sequencing on retinal samples collected at 4-h intervals (n&#xa0;=&#xa0;24 per group) from young (6-week-old) and aged (20-month-old) C57BL/6 mice maintained under a 12h:12h light-dark cycle. Differential expression analysis was performed using edgeR (FDR <0.05, |FC|&#xa0;>&#xa0;1.5). Rhythmicity analysis was conducted using the MetaCycle package, which integrates JTK_CYCLE and Lomb-Scargle algorithms, while differential rhythmicity analysis was performed using the CircaCompare package.<br><br>RESULTS: A total of 361 differentially expressed genes (DEGs) were identified between young and aging retinas, with enrichment in immunity-related pathways, including antigen processing and presentation, as well as the AGE-RAGE signaling pathway. A total of 4151 genes (16&#xa0;%) were identified as rhythmic expressed genes (REGs) in the young group, whereas 2999 genes (11&#xa0;%) were detected in the aging group. Notably, aging reduced rhythmic gene proportion by 28&#xa0;% (1152 genes). Additionally, aging altered rhythmic pathway dynamics: genes associated with RNA degradation and the proteasome pathway lost rhythmicity, whereas genes related to immune responses, and age-related macular degeneration (AMD)-associated pathways, including MAPK and WNT signaling, exhibited rhythmicity in the aging retina. In the differential rhythmicity analysis of 2036 overlapping rhythmic genes, 387 genes exhibited differences in MESOR, 78 showed differences in amplitude, and 72 displayed phase shifts.<br><br>CONCLUSIONS: Aging significantly reshapes the rhythmic transcriptome in the retina, altering both the composition and temporal distribution of rhythmic pathways. This study provides a valuable dataset elucidating the interplay between aging, diurnal rhythms, and gene expression in the retina, offering insights into potential molecular mechanisms underlying age-related retinal diseases.},
}
@article {pmid40591950,
year = {2025},
author = {Ferro Desideri, L and Anguita, R and Sacconi, R and Beretta, F and Corradetti, G and Feo, A and Dobovsek, D and Parravano, M and Capuano, V and Souied, E and Sarraf, D and Zinkernagel, M and Querques, G},
title = {UNILATERAL RETICULAR PSEUDODRUSEN: Clinical Features and Potential Protective Factors.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {11},
pages = {2049-2056},
doi = {10.1097/IAE.0000000000004575},
pmid = {40591950},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; *Retinal Drusen/diagnosis ; Male ; Female ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Choroid/blood supply/pathology ; Aged ; Fundus Oculi ; *Visual Acuity ; Multimodal Imaging ; Protective Factors ; },
abstract = {PURPOSE: To describe the demographic and clinical data of patients with rare unilateral reticular pseudodrusen (RPD) presentation and investigate features that may play a protective role against their formation.<br><br>METHODS: This retrospective, multicenter case series included patients with unilateral RPD from multiple tertiary care centers. Demographic, longitudinal clinical, and multimodal imaging (MMI) data were collected and compared between the study eye showing the presence of RPD and the fellow eye. Central macular thickness, subfoveal choroidal thickness, and choroidal vascular index were measured.<br><br>RESULTS: Ten eyes of 10 patients with unilateral RPD were included, with a mean age of 87.3 years (&#xb1;5.9). Fellow eyes exhibited four cases of retinal vein occlusion and one case of macular microaneurysm. Average baseline subfoveal choroidal thickness was 168.4 &#xb5; m (&#xb1;79.1) in the eyes presenting RPD, where it was 194.4 &#xb5; m (&#xb1;88.3) in the fellow eyes. Average choroidal vascular index at baseline was lower in RPD eyes (0.39, &#xb1;0.11) as opposed to 0.48 (&#xb1;0.03) in fellow eyes.<br><br>CONCLUSION: Our study highlights potential protective factors associated with unilateral RPD in age-related macular degeneration, emphasizing the crucial role played by the choroid and the choriocapillaris-retinal pigment epithelium complex.},
}
@article {pmid40591387,
year = {2025},
author = {Fursova, AZ and Nikulich, IF and Vasilyeva, MA and Derbeneva, AS and Karlash, YA},
title = {[New options determining the success of treatment for neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {3},
pages = {71-78},
doi = {10.17116/oftalma202514103171},
pmid = {40591387},
issn = {0042-465X},
mesh = {Humans ; Angiogenesis Inhibitors/administration &amp; dosage ; Dose-Response Relationship, Drug ; Intravitreal Injections/methods ; *Macular Degeneration/drug therapy/diagnosis ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that can lead to severe and irreversible vision loss despite the availability of effective anti-VEGF agents. One of the potential causes of suboptimal treatment outcomes in nAMD is undertreatment, which may result from the need for frequent injections and follow-up visits, limitations in public healthcare funding, and challenges in achieving sustained and long-term control of disease activity (DA). Aflibercept 8 mg is a novel formulation with a higher concentration and improved molecular stability, enabling a fourfold increase in the molar dose of the active substance delivered to the vitreous body. The phase III PULSAR trial, a 96-week randomized, double-masked, active-controlled study, evaluated the efficacy and safety of 8 mg aflibercept compared with the standard 2 mg dose in treatment-naïve patients with nAMD. Participants were randomized 1:1:1 into three groups: aflibercept 2 mg every 8 weeks (2q8), 8 mg every 12 weeks (8q12), or 8 mg every 16 weeks (8q16) after three initial monthly loading doses. The study demonstrated the benefits of the 8 mg dose in extending interinjection intervals. By week 96, 88% of patients achieved an interval of ≥12 weeks, 71% ≥16 weeks, and 47% ≥20 weeks; in the 8q16 group, 53% of patients reached an interval of ≥20 weeks and 31% - 24 weeks. Over the 2-year period, patients in the 8q16 group received approximately 8 injections, compared to around 13 in the 2q8 group, with comparable anatomical and functional outcomes and no additional safety concerns. Given the proven effectiveness in improving best-corrected visual acuity (BCVA), superior outcomes in resolving intra- and/or subretinal fluid (IRF/SRF), and reduced treatment burden, it appears optimal to broadly transition patients already receiving aflibercept 2 mg to the higher molar concentration (aflibercept 8 mg) regardless of treatment phase or the interinjection interval. This approach aims to achieve a longer anti-VEGF effect duration and sustained DA control with the fewest possible injections.},
}
@article {pmid40591046,
year = {2025},
author = {Cukurova, F and Izgi, B and Cebeci, Z and Kir, N},
title = {Long-term observational data on neovascular age-related macular degeneration: a 10-year follow-up study.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {273},
pmid = {40591046},
issn = {1573-2630},
mesh = {Humans ; Male ; Follow-Up Studies ; Female ; *Visual Acuity ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Time Factors ; Middle Aged ; *Ranibizumab/administration &amp; dosage ; Fluorescein Angiography/methods ; Fundus Oculi ; *Bevacizumab/administration &amp; dosage ; Aged, 80 and over ; Treatment Outcome ; *Macula Lutea/pathology ; },
abstract = {AIM: To report real-life data of eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors for an average of 10 years.<br><br>METHODS: Anti-VEGF na&#xef;ve eyes with nAMD and had at least 7-year follow-up at a tertiary center were evaluated. The primary outcome was a change in best-corrected visual acuity (BCVA) at 10&#xa0;years; secondary outcomes included anatomical outcomes, number of injections, and examinations.<br><br>RESULTS: The study included 102 eyes of 82 patients, with a mean initial age of 69.2&#x2009;&#xb1;&#x2009;9.7&#xa0;years. The average follow-up duration was 116.19&#x2009;&#xb1;&#x2009;24.98&#xa0;months, and the mean number of injections was 37.42&#x2009;&#xb1;&#x2009;15.81. Initial mean BCVA was 59.0&#x2009;&#xb1;&#x2009;18.3 letters, increasing to 70.55&#x2009;&#xb1;&#x2009;12.72 in the first year, then gradually declining to 60.44&#x2009;&#xb1;&#x2009;17.55 by the tenth year. Patients had an average of 6.13&#x2009;&#xb1;&#x2009;1.72 exams in the first year and 4.61&#x2009;&#xb1;&#x2009;2.60 in the last year, with 6.02&#x2009;&#xb1;&#x2009;1.70 injections in the first year and 3.18&#x2009;&#xb1;&#x2009;2.17 in the tenth year. Patients were classified as increasing, decreasing, or stable based on changes in VA by 2 lines or 10 letters. Significant variables among the groups included age (p&#x2009;=&#x2009;0.018), baseline BCVA (p&#x2009;=&#x2009;0.001), prior photodynamic therapy (PDT) (p&#x2009;=&#x2009;0.025), and retinal hemorrhage due to macular neovascularization (MNV) (p&#x2009;=&#x2009;0.049).<br><br>CONCLUSION: Eyes with nAMD maintained their initial BCVA after treatment with VEGF inhibitors for 10&#xa0;years. With regular and prompt treatment, functional vision can be achieved over a long period of time in nAMD.},
}
@article {pmid40588681,
year = {2025},
author = {Shu, Y and Li, Z and Zong, T and Mu, T and Zhou, H and Yang, Q and Wu, M and Liu, Y and Xie, T and Tan, C and Zhuang, M and Wang, X and Yao, Y},
title = {MiR-21-5p promotes RPE cell necroptosis by targeting Peli1 in a rat model of AMD.},
journal = {In vitro cellular &amp; developmental biology. Animal},
volume = {61},
number = {7},
pages = {801-815},
pmid = {40588681},
issn = {1543-706X},
support = {2020-THRCTD-1//Wuxi Taihu Lake Talent Plan, Supports for Leading Talents in Medical and Health Profession/ ; HRC-DJ-1//Wuxi Taihu Lake Talent Plan, Supports for Leading Talents in Medical and Health Profession/ ; BJ2023001//Top Talent Support Program for young and middle-aged people of Wuxi Health Committee/ ; HB2023014//Top Talent Support Program for young and middle-aged people of Wuxi Health Committee/ ; WMCG202347//General Program of Wuxi Medical Center, Nanjing Medical University/ ; WMCG202345//General Program of Wuxi Medical Center, Nanjing Medical University/ ; ZDXK2021001//Medial Key Discipline Program of Wuxi Health Commission/ ; NMUB20230240//The Science and Technology Development Fund Project of Nanjing Medical University/ ; },
mesh = {Animals ; *MicroRNAs/genetics/metabolism ; *Retinal Pigment Epithelium/pathology/metabolism ; Disease Models, Animal ; *Necroptosis/genetics/drug effects ; *Macular Degeneration/genetics/pathology ; Rats ; Male ; Rats, Sprague-Dawley ; Iodates ; Humans ; },
abstract = {Nonexudative age-related macular degeneration (dry AMD) is characterized by the progressive degeneration of retinal pigment epithelial (RPE) cells and photoreceptors, resulting in central vision loss. The disease is primarily marked by the accumulation of drusen and RPE atrophy. Given the emerging role of miR-21-5p in various ocular diseases, including diabetic retinopathy, glaucoma, pterygium, and choroidal neovascularization, we hypothesized that miR-21-5p may also impact RPE cell integrity in AMD. To test this hypothesis, we employed a rat model of dry AMD induced by sodium iodate (NaIO3) and evaluated the effects of miR-21-5p modulation via intravitreal injections of miR-21-5p agomir or antagomir. Comprehensive assessments were performed using optical coherence tomography (OCT), fundus imaging, histopathology, and biochemical markers. Our results demonstrated an upregulation of miR-21-5p in response to NaIO3 treatment. Administration of miR-21-5p agomir exacerbated RPE damage, while pretreatment with miR-21-5p antagomir mitigated these detrimental effects. Furthermore, in vitro experiments revealed that miR-21-5p regulates necroptosis in CoCl2-treated RPE cells by targeting Pellino1 (Peli1) via its 3' untranslated region, thereby inhibiting Peli1 expression. Overexpression of Peli1 effectively counteracted the necroptotic effects induced by CoCl2. These findings highlight the potential of miR-21-5p as a therapeutic target in dry AMD, expanding our understanding of miRNA-mediated regulation of RPE cells and suggesting new avenues for treatment strategies.},
}
@article {pmid40588392,
year = {2025},
author = {Lin, C and Jivraj, S},
title = {Are diabetes and blood sugar control associated with the diagnosis of eye diseases? An English prospective observational study of glaucoma, diabetic eye disease, macular degeneration and cataract diagnosis trajectories in older age.},
journal = {BMJ open},
volume = {15},
number = {6},
pages = {e091816},
pmid = {40588392},
issn = {2044-6055},
mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; England/epidemiology ; *Cataract/epidemiology/diagnosis ; *Glaucoma/epidemiology/diagnosis ; *Macular Degeneration/epidemiology/diagnosis ; Risk Factors ; *Diabetic Retinopathy/epidemiology/diagnosis ; Middle Aged ; Glycated Hemoglobin/analysis ; Blood Glucose ; Aged, 80 and over ; *Glycemic Control ; *Diabetes Mellitus/epidemiology/blood ; Logistic Models ; Longitudinal Studies ; },
abstract = {BACKGROUND: The growing global burden of diabetes suggests a currently unrealised growth in prevalence of eye disease. This prospective observational study addresses gaps in evidence of blood sugar control as a risk factor for the diagnosis of glaucoma, diabetic eye disease, macular degeneration and cataract using waves 2-9 (2004-2019) of the English Longitudinal Study of Ageing.<br><br>METHODS: Logistic regression modelling is used to predict the probability of self-reported diagnosis of four eye conditions separately over a 14-year period in a community-dwelling sample in England. Analysis of approximately 29&#x2009;000 person observations over eight study waves from around 5600 participants for each eye disease is conducted with an average of 5.7 waves per participant. Participants' baseline blood sugar control is categorised as non-diabetic (diabetes not previously diagnosed and glycated haemoglobin (HbA1c)<6.5), controlled (diabetes previously diagnosed and HbA1c<6.5), uncontrolled (diabetes previously diagnosed and HbA1c&#x2265;6.5) and undiagnosed (diabetes not previously diagnosed and HbA1c&#x2265;6.5). Controls at baseline for age, sex, physical activity level, body mass index and smoking status are included in the regression analysis.<br><br>RESULTS: The mean age of the sample is 66 and 53% are female. The main finding from this study is that older adults in England who are controlling a diabetes diagnosis have a lower probability of developing glaucoma, diabetic eye disease or macular degeneration compared with those either without a diabetes diagnosis or with uncontrolled diabetes. Compared with those with controlled diabetes, the adjusted odds of developing glaucoma was 1.29 times higher (95%&#x2009;CI 1.01 to 1.65) among those not diabetic; the adjusted odds of developing diabetic eye disease was 1.20 times higher (95%&#x2009;CI 1.00 to 1.45) among those with uncontrolled diabetes; and the adjusted odds of developing macular degeneration was 1.38 times higher (95%&#x2009;CI 1.04 to 1.82) among those with undiagnosed diabetes. There was no statistically significant difference in the probability of developing cataracts by category of blood sugar control.<br><br>CONCLUSION: This study illustrates the importance of blood sugar control in the development of eye diseases and therefore supports more regular screening measures for eye disease in older age among groups at risk of diabetes.},
}
@article {pmid40588359,
year = {2025},
author = {Weatherby, TJM and Boyle, M and Madhusudhan, S},
title = {Charles Bonnet syndrome in adults with inherited retinal disease: prevalence and patient perspectives.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40588359},
issn = {2397-3269},
mesh = {Humans ; Female ; Male ; Prevalence ; Adult ; Cross-Sectional Studies ; Middle Aged ; Surveys and Questionnaires ; *Charles Bonnet Syndrome/epidemiology/psychology/etiology/diagnosis ; Prospective Studies ; *Retinal Diseases/epidemiology/complications/diagnosis ; Aged ; Visual Acuity ; United Kingdom/epidemiology ; Young Adult ; *Hallucinations/epidemiology/etiology ; },
abstract = {OBJECTIVE: To assess the prevalence of symptoms associated with Charles-Bonnet syndrome (CBS) in adult patients with inherited retinal disease (IRD) and explore patient perspectives and need for support.<br><br>METHODS AND ANALYSIS: This was a prospective single-centre cross-sectional service evaluation and improvement project that involved adult patients with a clinical diagnosis of IRD under the care of the specialist IRD service at a tertiary NHS healthcare provider in the UK. Information was gathered from a survey questionnaire completed by participants remotely or at a hospital appointment and electronic patient records.<br><br>RESULTS: There were 103 surveys returned of which 94 were suitable for inclusion in the analysis. Visual hallucinations were reported by 18.6% of patients overall. Patients with visual acuity worse than 0.3 logMAR made up 76% of those reporting CBS symptoms.Of the patients who experienced visual hallucinations, 59% reported that their visual hallucinations had no effect on them, while 29% reported a negative effect, with 12% not commenting; only 12% said that they require further support.<br><br>CONCLUSION: CBS symptoms were reported by almost one in six patients in our IRD practice.Only a small proportion of patients included in this survey felt that they required additional support, but they did express that being informed early on of an explanation for their visual hallucinations was helpful.The limitations of our study are the small number of patients included in the survey, the lack of external validation of the questionnaire used, the risk of selection bias and the two different methods/phases of data collection used.},
}
@article {pmid40587704,
year = {2025},
author = {Polat Gültekin, B and Çomçali, S and Şahin, E},
title = {Assessment of inflammation levels through the modified systemic inflammation score in patients with nonneovascular and neovascular age-related macular degeneration.},
journal = {Medicine},
volume = {104},
number = {26},
pages = {e43047},
pmid = {40587704},
issn = {1536-5964},
mesh = {Humans ; Male ; Female ; Aged ; *Inflammation/blood/diagnosis ; *Macular Degeneration/blood/complications ; Severity of Illness Index ; Middle Aged ; Aged, 80 and over ; Serum Albumin/analysis ; *Wet Macular Degeneration ; Body Mass Index ; },
abstract = {This study assesses the inflammation levels through the modified systemic inflammation score (mSIS) in patients with nonneovascular and neovascular age-related macular degeneration (AMD). A total of 90 participants were categorized into 3 groups: a control group, individuals with nonneovascular AMD under follow-up, and individuals with neovascular AMD who had not yet started injection treatment. Demographic and clinical parameters, including body mass index, were analyzed. The mSIS, based on serum albumin levels and the lymphocyte-to-monocyte ratio, was used to determine the level of systemic inflammation. There were no significant differences between the groups in terms of age (P = .08) or gender (P = .06). Regarding body mass index, no significant differences were observed between the groups (P = .06). When comparing mSIS scores between the groups, no significant differences were found for mSIS scores 0 and 1 across the groups. However, for mSIS 2, the proportion of participants with an mSIS score of 2 was significantly higher in the neovascular AMD group compared with the control group (P = .01). These findings suggest that mSIS may be a valuable tool for assessing systemic inflammation in AMD. The higher mSIS scores in the neovascular AMD group may indicate that disease severity is associated with increased inflammation. Further large-scale studies are needed to confirm the utility and clinical relevance.},
}
@article {pmid40585168,
year = {2025},
author = {Seddon, JM and De, D and Rosner, B},
title = {Quantifying Effects of Lifestyle Changes on Progression to Advanced Age-Related Macular Degeneration in High Genetic Risk Individuals.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40585168},
support = {R01 EY011309/EY/NEI NIH HHS/United States ; R01 EY022445/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: We examined the extent to which adopting healthy lifestyle behaviors could offset high genetic risk for progression to advanced age-related macular degeneration (AMD), to address concerns of family members of affected patients.<br><br>DESIGN: Prospective longitudinal study.<br><br>PARTICIPANTS: Eyes with early or intermediate AMD at baseline were defined based on the Age-Related Eye Disease Study severity scale. High genetic risk was defined as the third tertile of a genetic risk score for progression, adjusted for age, race and sex.<br><br>METHODS: Information on lifestyle behaviors was obtained from baseline risk and food frequency questionnaires. Risk-inducing and health-promoting lifestyle profiles were defined based on dichotomous categorizations of smoking, body-mass index (BMI), and dietary caloric intake, green leafy vegetables and fish, in never and ever smokers. Cox proportional hazard ratios (HRs), relative risks (RRs) and population attributable risks (PARs) were calculated, adjusting for inter-eye correlation, demographic factors, macular status and family history.<br><br>MAIN OUTCOME MEASURES: Progression to advanced AMD (AAMD) and subtypes geographic atrophy (GA) and neovascular (NV), confirmed at 2 consecutive visits over 5 years of follow-up.<br><br>RESULTS: Among 898 high genetic risk eyes, 207 eyes progressed to AAMD (23%). Among never smokers, a high risk-inducing lifestyle profile conferred a 3-fold increased incidence of AAMD, compared to an ideal health-promoting lifestyle profile [HR = 3.3 (CI 1.8, 6.4), P <0.001]. In ever smokers, a risk-inducing profile was independently associated with a 5-fold increased incidence of AAMD [HR = 5.3 (CI 2.3,11.9), P <0.001]. Stronger effects of these lifestyle behaviors were seen for GA compared to NV. Estimated PARs suggested adopting an ideal health-promoting profile could prevent 56% of incident AAMD in never smokers and 60% in ever smokers.<br><br>CONCLUSION: Unhealthy behaviors increased incidence of AAMD by 3 to 5-fold among a highly genetically susceptible population, and 56-60% of AAMD incidence was attributed to the modifiable factors of smoking, high BMI, high caloric intake and low intake of foods rich in lutein-zeaxanthin and omega-3 fatty acids. These results underscore the importance of lifestyle interventions even in high genetic risk populations, such as relatives of affected patients, to reduce progression from early and intermediate AMD to advanced vision-threatening stages.},
}
@article {pmid40584817,
year = {2025},
author = {Wang, W and Wang, N and Zhao, X and Su, X and Liu, Z},
title = {Recent advancements in polymer science for retinal diseases: New frontiers in drug delivery systems.},
journal = {APL bioengineering},
volume = {9},
number = {2},
pages = {020902},
pmid = {40584817},
issn = {2473-2877},
abstract = {Retinal diseases, such as age-related macular degeneration and diabetic macular edema, are significant contributors to vision loss. While injection of anti-vascular endothelial growth factors is the current gold standard treatment, their invasive nature reduces patient compliance and treatment outcomes and increases the risk of complications. In this review, we explore the recent advancements in drug delivery systems designed to overcome ocular barriers to effectively deliver drugs to the retina. We examine advancements in intravitreal injections, such as novel formulations, therapeutic molecules, and sustained-release implants. Moreover, we discuss innovations in noninvasive strategies, such as topical delivery systems incorporating cell-penetrating peptides, solid lipid nanoparticles, dendrimers, and nano-micelles. These technologies aim to enhance drug penetration, stability, and bioavailability. Although preclinical and clinical trials have yielded promising results, challenges remain in ensuring long-term safety and efficacy. This review highlights future research directions to optimize these approaches and develop more effective, patient-friendly therapies for retinal diseases.},
}
@article {pmid40584705,
year = {2025},
author = {Elvira, JC and Devesa, P and Elvira-Giner, B and Tañá-Sanz, P and Orts-Vila, P and Tañá-Rivero, P},
title = {Visual outcomes with a non-diffractive enhanced depth-of-focus IOL in patients with age-related macular degeneration.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1505401},
pmid = {40584705},
issn = {2296-858X},
abstract = {PURPOSE: To evaluate visual function in eyes with age-related macular degeneration (AMD) implanted with a non-diffractive enhanced depth-of-focus (EDOF) intraocular lens (IOL) after cataract surgery.<br><br>DESIGN: Prospective, observational, non-randomized clinical study.<br><br>METHODS: Twenty-two eyes from 22 patients diagnosed with AMD and cataracts were submitted to standard cataract surgery with a non-diffractive EDOF IOL implantation (AcrySof IQ Vivity). We measured monocular uncorrected and best-corrected-distance visual acuity (UDVA and CDVA), uncorrected- and distance-corrected-intermediate visual acuity (UIVA and DCIVA), uncorrected- and distance-corrected-near visual acuity (UNVA and DCNVA), manifest refractive spherical equivalent (MRSE) and cylinder, monocular defocus curve and patient-reported outcome questionnaires (Catquest-9SF and NEI VFQ-25). Follow-up visits were carried out at 1, 3 and 6 months post-surgery.<br><br>RESULTS: At 6 months post-surgery all eyes were within &#xb1; 0.50 D with a mean MRSE of -0.19 &#xb1; 0.20 D, 95.45% had a refractive cylinder of &#x2264; 0.50 D with a mean cylinder of -0.24 &#xb1; 0.27 D. The mean values of postoperative monocular CDVA, DCIVA, and DCNVA were 0.02 &#xb1; 0.08, 0.16 &#xb1; 0.11, and 0.26 &#xb1; 0.15 logMAR, respectively. The defocus curve showed good visual acuity at distance and intermediate with a depth-of-focus of about 1.60 D. A total of 81.82% of patients did not report any difficulty with their vision in their everyday-life and 86.36% reported being quite satisfied to very satisfied with their current vision. The NEI VFQ-25 showed that all values improved significantly (p < 0.05) after the surgery in the different parameters analyzed except for ocular pain (p = 0.390) and color vision (p = 0.333).<br><br>CONCLUSION: The use of a non-diffractive EDOF IOL in AMD eyes with cataracts is a safe and effective surgical approach for visually correcting aphakia, providing good visual acuity at far and intermediate distances. Our outcomes support the use of non-diffractive EDOF IOLs in patients with AMD diagnosed with cataracts aiming to obtain spectacle-independence at far and intermediate distances.},
}
@article {pmid40582342,
year = {2025},
author = {Zur, D and Wright, DM and Shahar Gonen, M and Shor, R and Wen, Q and Benyamini, G and Havilio, M and Ben-Nun, M and Look, S and Dor, O and Chakravarthy, U and Loewenstein, A and Peto, T},
title = {The British-Israeli Project for Algorithm-Based Management of Age-Related Macular Degeneration: Deep Learning Integration for Real-World Data Management and Analysis.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {248},
number = {4},
pages = {294-307},
pmid = {40582342},
issn = {1423-0267},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Angiogenesis Inhibitors/administration &amp; dosage ; *Deep Learning ; *Disease Management ; *Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Israel/epidemiology ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; United Kingdom/epidemiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; Feasibility Studies ; },
abstract = {INTRODUCTION: The aim of this study was to describe the development of an integrative dataset, combining clinical and optical coherence tomography (OCT) imaging data by applying a deep learning (DL) algorithm for automated, objective, and comprehensive quantification of OCT scans in two large real-world datasets of eyes with neovascular age-related macular degeneration (nAMD). We further report baseline characteristics of the study population, focusing on demographics, clinical parameters, and quantitative retinal morphological features.<br><br>METHODS: This retrospective study analyzed data from 5,207 eyes of 4,265 nAMD patients treated at two centers in the UK and Israel. Longitudinal clinical data and OCT scans were analyzed using a DL algorithm (NOA&#x2122;, Notal Ltd.) to quantify retinal fluid volumes and morphological features. Baseline characteristics were compared between the cohorts.<br><br>RESULTS: The dataset included 134,340 visual acuity (VA) measurements, 79,457 OCT scans, and 73,218 anti-vascular endothelial growth factor injections. Median follow-up was 4.54 years (UK) and 3.12 years (Israel). Baseline VA differed significantly between cohorts due to varying treatment criteria. Fluid distribution patterns were similar, with most eyes showing combined intraretinal and subretinal fluid. Age-related trends in fluid volumes were observed. Weak correlations were found between baseline OCT measurements and VA.<br><br>CONCLUSION: This study demonstrates the feasibility of integrating large-scale clinical and imaging data for automated analysis in nAMD. The comprehensive baseline characterization provides insights into real-world presentations and lays the groundwork for enabling personalized decision-making and optimizing outcomes based on individual patient profiles and fluid distribution patterns.},
}
@article {pmid40581633,
year = {2025},
author = {Salkar, A and Palanivel, V and Basavarajappa, D and Mirzaei, M and Schulz, A and Yan, P and Gupta, V and Graham, S and You, Y},
title = {Glial and immune dysregulation in glaucoma independent of retinal ganglion cell loss: a human post-mortem histopathology study.},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {141},
pmid = {40581633},
issn = {2051-5960},
abstract = {UNLABELLED: Glaucoma is characterized by progressive retinal ganglion cell (RGC) loss and optic nerve head (ONH) changes, but the roles of glial activation and immune responses remain unclear. This study examines gliosis, microglial diversity, and inflammation in postmortem retinal tissues. Postmortem retinal and ONH samples (total n = 50) from patients with open-angle glaucoma (G, n = 18) were compared with those from age-matched controls (n = 32), including healthy individuals (Ctrl) and disease controls (patients with early age-related macular degeneration [AMD] and diabetes mellitus [DM]). Immunostaining was performed to assess glial activation, blood–retinal barrier (BRB) integrity, and immune infiltration, which were quantified via ImageJ and Zen lite. Generalized estimating equations (GEEs) with Bonferroni correction accounted for intrapatient variability. G retinae presented significant RGC loss accompanied by widespread gliosis, with activation of microglia (Iba1), astrocytes (GFAP), and Müller cells (Vimentin). This gliotic response differed across conditions, with astrocyte activation being more prominent in DM and microglial activation predominating in AMD. In glaucoma, gliosis is evident even in early-stage disease, regardless of the severity of retinal ganglion cell (RGC) loss or structural changes in the ONH. Furthermore, microglia showed a marked shift in morphological diversity, transitioning to hyperramified, bushy, and amoeboid forms, along with an increased distribution of activation markers such as CD45, CD11b, and CD163. Additionally, biochemical evidence of alterations to the BRB integrity, characterized by reduced tight junction protein expression, facilitates immune cell infiltration, as indicated by the minimal and inconsistent presence of CD3/CD4+ T cells. Gliosis persisted regardless of RGC loss severity, suggesting that gliosis progresses independently of neuronal degeneration. Unlike AMD and DM, where specific glial subtypes dominate, glaucoma exhibits widespread gliosis. Microglial heterogeneity indicates the existence of a continuum of functional states. Furthermore, dysregulation of the BRB, inconsistent immune infiltration, and multimodal microglial activation indicate that the inflammatory response in glaucoma patients is driven primarily by resident microglia, with limited interactions with infiltrating immune cells. These findings highlight the need for further research into glial modulation as a potential therapeutic strategy.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-025-02066-0.},
}
@article {pmid40581196,
year = {2025},
author = {Icoz, SGG and Usta, SA and Icoz, M},
title = {Post-phacoemulsification examination of intraocular pathologies that could not bedetected by fundus biomicroscopy or OCT in eyes with dense cataract: trying to avoid intra- and post-operative complications.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {54},
number = {},
pages = {104696},
doi = {10.1016/j.pdpdt.2025.104696},
pmid = {40581196},
issn = {1873-1597},
mesh = {Humans ; Female ; Aged ; Male ; Middle Aged ; *Phacoemulsification/adverse effects/methods ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Aged, 80 and over ; *Postoperative Complications/prevention &amp; control ; *Cataract/complications ; Adult ; Lens Implantation, Intraocular ; Risk Factors ; },
abstract = {PURPOSE: To investigate postoperative intraocular pathologies in eyes with dense cataracts that preclude fundus evaluation.<br><br>DESIGN: Retrospective study.<br><br>METHODS: This study was conducted on 88 eyes from 88 patients.All participants underwent uncomplicated phacoemulsification and intraocular lens implantation due to dense cataracts that prevented fundus evaluation in biomicroscopic dilated fundus examination. In the postoperative first-month follow-up, intraocular pathologies were assessed via dilated biomicroscopic fundus examination, color fundus photography, and optical coherence tomography.Potential risk factors were identified using univariate and multivariate regression analyses.<br><br>RESULTS: The mean age of the patients was 69 &#xb1; 11 (range:28-92) years, with 49 being female. Intraocular pathologies were detected in 33 patients (37 %).The most frequently observed pathologies were diabetic retinopathy (n = 11, 13 %), followed by age-related macular degeneration (n = 7, 8 %), epiretinal membrane (n = 6, 7 %), full-thickness or lamellar macular holes (n = 3, 3 %), photoreceptor damage (n = 2, 2 %), glaucomatous changes (n = 2, 2 %), myopic degeneration (n = 1, 1 %), and vitreomacular traction (n = 1, 1 %).Both univariate and multivariate regression analyses revealed diabetes mellitus and the presence of pathology in the fellow eye as significant risk factors for postoperative intraocular pathologies in patients with dense cataracts (p < 0.05 and p < 0.001,respectively).<br><br>CONCLUSION: A considerable proportion of intraocular pathologies were detected postoperatively in eyes with dense cataracts.Diabetes mellitus and the presence of pathology in the fellow eye were found to be significant risk factors for postoperative intraocular pathologies in both univariate and multivariate regression analyses.These findings provide valuable evidence for clinicians and patients regarding postoperative intraocular pathologies in eyes with mature cataracts.},
}
@article {pmid40581140,
year = {2025},
author = {Hammer, M and Oertel, J and Alderzy, H and Tarhan, M and Meller, D and Curcio, CA},
title = {Fundus autofluorescence intensity, lifetime, and spectral imaging in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110500},
doi = {10.1016/j.exer.2025.110500},
pmid = {40581140},
issn = {1096-0007},
mesh = {Humans ; *Macular Degeneration/diagnosis ; *Fluorescein Angiography/methods ; *Optical Imaging/methods ; Fundus Oculi ; Retinal Pigment Epithelium/pathology ; },
abstract = {Fundus autofluorescence (FAF) imaging is a well-established retinal imaging technique that is widely used in the diagnostics of age-related macular degeneration (AMD). It facilitates the classification of distinct autofluorescence patterns, which may be predictive of AMD progression, the quantification of atrophic zones and their development over time and serves as a clinical endpoint in various studies. However, beyond autofluorescence intensity, emission spectra and fluorescence lifetime can be utilized to further investigate specific fluorophores, their changes in association with AMD, and their potential prognostic value in disease progression and therapy monitoring. In this review, we present the current state of spectrally and temporally resolved retinal FAF imaging in AMD. We explain the underlying principles, review the applied techniques, propose possible fluorophores contributing to FAF, summarize results from clinical studies as well as from histology and investigations in both in vivo and in vitro AMD models, and discuss the limitations of current techniques along with perspectives for technical development and clinical application.},
}
@article {pmid40580986,
year = {2025},
author = {, },
title = {Global burden of vision impairment due to age-related macular degeneration, 1990-2021, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021.},
journal = {The Lancet. Global health},
volume = {13},
number = {7},
pages = {e1175-e1190},
pmid = {40580986},
issn = {2214-109X},
mesh = {Humans ; *Macular Degeneration/epidemiology/complications ; *Global Burden of Disease/trends ; *Global Health/statistics &amp; numerical data ; Male ; Female ; Aged ; Disability-Adjusted Life Years ; Middle Aged ; Risk Factors ; Prevalence ; Forecasting ; *Vision Disorders/epidemiology/etiology ; Aged, 80 and over ; Quality-Adjusted Life Years ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a growing public health concern worldwide, as one of the leading causes of vision impairment. We aimed to estimate global, national, and region-specific prevalence and disability-adjusted life-years (DALYs) along with tobacco as a modifiable risk factor to aid public policy addressing AMD.<br><br>METHODS: Data on AMD were extracted from the Global Burden of Disease, Injuries, and Risk Factor Study 2021 database in 204 countries and territories, 1990-2021. Vision impairment was defined and categorised by severity as follows: moderate to severe vision loss (visual acuity from <6/18 to 3/60) and blindness (visual acuity <3/60 or a visual field <10 degrees around central fixation). The burden of vision impairment attributable to AMD was subsequently estimated. These estimates were further stratified by geographical region, age, year, sex, Healthcare Access and Quality (HAQ) Index, and Socio-demographic Index (SDI) levels. Additionally, the effect of tobacco use, a modifiable risk factor, on the burden of AMD was analysed, and projections of AMD burden were estimated through to 2050. These projections also included scenario modelling to assess the potential effects of tobacco elimination.<br><br>FINDINGS: Globally, the number of individuals with vision impairment due to AMD more than doubled, rising from 3&#xb7;64 million (95% uncertainty inverval [UI] 3&#xb7;04-4&#xb7;35) in 1990 to 8&#xb7;06 million (6&#xb7;71-9&#xb7;82) in 2021. Similarly, DALYs increased by 91% over the same period, from 0&#xb7;30 million (95% UI 0&#xb7;21-0&#xb7;42) to 0&#xb7;58 million (0&#xb7;40-0&#xb7;80). By contrast, age-standardised prevalence and DALY rates declined, with prevalence rates decreasing by 5&#xb7;53% (99&#xb7;50 per 100&#x2008;000 of the population [95% UI 83&#xb7;16-118&#xb7;04] in 1990 to 94&#xb7;00 [78&#xb7;32-114&#xb7;42] in 2021) and DALY rates dropping by 19&#xb7;09% (8&#xb7;38 [5&#xb7;70-11&#xb7;53] to 6&#xb7;78 [4&#xb7;70-9&#xb7;32]). These rates showed a consistent decrease in higher SDI quintiles, reflecting the negative correlation between HAQ Index and AMD burden. A general downward trend was observed from 1990 to 2021, with the largest age-standardised reduction occurring in the low-middle SDI quintile. The global contribution of tobacco to age-standardised DALYs decreased by 20%, declining from 12&#xb7;45% (95% UI 7&#xb7;73-17&#xb7;37) in 1990 to 9&#xb7;96% (6&#xb7;12-14&#xb7;06) in 2021. By 2050, the number of individuals affected by AMD is projected to increase from 3&#xb7;40 million males (95% UI 2&#xb7;81-4&#xb7;17) in 2021 to 9&#xb7;02 million (5&#xb7;72-14&#xb7;20) and from 4&#xb7;66 million females (3&#xb7;88-5&#xb7;65) to 12&#xb7;32 million (8&#xb7;88-17&#xb7;08). Eliminating tobacco use could reduce these numbers to 8&#xb7;17 million males (5&#xb7;59-11&#xb7;92) and 11&#xb7;15 million females (8&#xb7;58-14&#xb7;48) in 2050.<br><br>INTERPRETATION: While the total prevalence and DALYs due to AMD have steadily increased from 1990 to 2021, age-standardised prevalence and DALY rates have declined, probably reflecting the effect of population ageing and growth. The consistent decrease in age-standardised rates with higher SDI levels highlights the crucial role of health-care resources and public policies in mitigating AMD-related vision impairment. The downward trend observed from 1990 to 2021 might also be partially attributed to the reduced effect of tobacco as a modifiable risk factor, with declines in tobacco use seen globally and across all SDI quintiles. The burden of vision impairment due to AMD is projected to increase to about 21&#xb7;34 million in 2050. However, effective tobacco regulation has the potential to substantially reduce AMD-related vision impairment, particularly in lower SDI quintiles where health-care resources are limited.<br><br>FUNDING: Gates Foundation.},
}
@article {pmid40580375,
year = {2025},
author = {Tabano, D and Watane, A and Gale, R and Cox, O and Hill, SR and Longworth, L and Oluboyede, Y and Ahmed, A and Patel, NA},
title = {The Economic Burden of Anti-Vascular Endothelial Growth Factor on Patients and Caregivers in the UK, Europe, and North America.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {8},
pages = {1869-1892},
pmid = {40580375},
issn = {2193-8245},
abstract = {INTRODUCTION: Intravitreal (IVT) injections of anti-vascular endothelial growth factor (VEGF) agents are the standard of care for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). While demonstrated to be effective, these treatments potentially place a significant burden on patients owing to their cost and frequency of treatment visits required for administration. The objective of this study was to investigate the economic burden of treatment on patients with nAMD/DME and their informal caregivers in seven countries.<br><br>METHODS: Data were collected from patients and caregivers in the USA, UK, Canada, Italy, Spain, Germany, and France using a survey between September and December 2022. Each survey collected data to facilitate calculating economic burden, combining the total financial costs (i.e., direct costs to receive treatment) and productivity losses associated with attending treatment appointments over a 6-month period. Quality of life data were collected using validated instruments.<br><br>RESULTS: In total, 194 patients and 194 caregivers reported currently receiving (or caring for someone who receives) anti-VEGF treatment. Across all countries, the modal frequency of anti-VEGF treatment was every 4&#xa0;weeks, except for patients with DME (every 8&#xa0;weeks). The largest, mean 6-month economic burden on the pooled population of patients with nAMD/DME was reported in Italy (&#x20ac;1244) and on caregivers it was in the USA (&#x20ac;3069). Economic burden was lower for respondents receiving fewer anti-VEGF injections.<br><br>CONCLUSIONS: More durable therapies for nAMD/DME would reduce treatment burden and have a sizeable impact financially on patients with nAMD/DME and their caregivers.},
}
@article {pmid40580349,
year = {2025},
author = {Nilsson, I and Senra, H and Baskaran, K and Mohlin, C and Macedo, AF},
title = {Perceived stress levels among patients treated for neovascular age-related macular degeneration with anti-VEGF injections.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {9},
pages = {2523-2531},
pmid = {40580349},
issn = {1435-702X},
mesh = {Humans ; Aged ; Male ; Female ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/psychology/diagnosis ; *Stress, Psychological/psychology/etiology ; Surveys and Questionnaires ; Aged, 80 and over ; *Ranibizumab/administration &amp; dosage ; *Bevacizumab/administration &amp; dosage ; Tomography, Optical Coherence ; Follow-Up Studies ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Middle Aged ; },
abstract = {PURPOSE: The aim of this study was to assess perceived stress levels in patients with nAMD undergoing treatment with anti-VEGF injections, and to investigate psychosocial and visual factors that can be associated with perceived stress among these patients.<br><br>METHODS: We recruited 202 patients diagnosed with nAMD (mean age of 78 years) who had received three or more anti-VEGF injections and had been scheduled for further treatments. To measure perceived stress, participants completed the Perceived Stress Scale-10 (PSS10). For the associated factors, the participants also completed the National Eye Institute Visual Function Questionnaire-25 and Multidimensional Perceived Social Support. Participants completed the questionnaires at home before an upcoming treatment scheduled at the hospital. Best corrected visual acuity was measured at the hospital before the treatment. Factors associated with PSS10 scores were examined using multiple regression models.<br><br>RESULTS: Participants with near vision impairment perceived higher stress levels than those without near vision impairment (p&#x2009;=&#x2009;0.034). Younger age (&#x3b2; = -0.15, p&#x2009;=&#x2009;0.003), better visual acuity (&#x3b2; = -4.20, p&#x2009;=&#x2009;0.036), poorer perceived social support (&#x3b2; = -1.21, p&#x2009;<&#x2009;0.001), and poorer self-reported visual function (&#x3b2; = -0.16, p&#x2009;<&#x2009;0.001) were significantly associated with increased levels of perceived stress.<br><br>CONCLUSIONS: Our study highlighted factors potentially associated with increased perceived stress in nAMD patients undergoing anti-VEGF treatment. Self-reported visual function, in particular near-vision, and perceived social support are factors that can be addressed to reduce the levels of stress and risk of mental health disorders in this patient group.},
}
@article {pmid40578594,
year = {2025},
author = {Shen, W and Tan, Y and Luo, Z and Jin, K and Ye, J},
title = {Elucidating the genetic and metabolomic underpinnings of age-related macular degeneration through two-sample Mendelian randomization.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110491},
doi = {10.1016/j.exer.2025.110491},
pmid = {40578594},
issn = {1096-0007},
mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; *Metabolomics/methods ; *Polymorphism, Single Nucleotide ; Aged ; *Wet Macular Degeneration/genetics/metabolism ; Male ; Female ; *Geographic Atrophy/genetics/metabolism ; *Macular Degeneration/genetics/metabolism ; Linkage Disequilibrium ; },
abstract = {Age-related macular degeneration (AMD), a chronic and progressive retinal disorder, is a leading cause of severe and irreversible visual impairment. The pathogenesis of AMD is multifactorial and intricate. Mendelian randomization (MR) serves as a popular approach of instrumental variable analysis to decipher the causality of associations. We applied a two-sample MR to assess the causal effects of 1400 serum metabolites and two subtypes of AMD (dry AMD and wet AMD) using the genome-wide association study statistics. We performed the inverse variance weighted method, weighted median algorithm, and sensitivity analyses including Cochran Q test, MR-Egger intercept test, MR-PRESSO, radial MR, leave-one-out examination, and Steiger test. Meanwhile, we utilized the linkage disequilibrium score regression analysis to consolidate the genetic correlation analysis. 18 identified metabolites for dry AMD and 16 for wet AMD were confirmed to have significant associations with the risk of dry AMD and wet AMD, respectively. Among these metabolites, 13 and 12 genetically established metabolites had prominent correlations after strict sensitivity assessments. 4 and 3 metabolites were identified prominent heritability for two subtypes of AMD, respectively. After excluding one metabolite which displayed shared genetic interrelation with wet AMD, our results demonstrates 4 identified serum metabolites are related to a reduced risk of dry AMD (N-acetyl-2-aminooctanoate, N-acetyl-L-glutamine, N-acetylphenylalanine, and N2,N5-diacetylornithine); 2 chemically known serum metabolites are linked with a decreased risk of wet AMD (pregnenetriol disulfate and N2-acetyl,N6,N6-dimethyllysine), respectively. The results manifested their potential protective roles in the development of AMD, underlines the distinct genetic inferences between metabolomics and AMD, and provide a novel ponder angle for clinical screening, preventive measures, and therapeutic strategy exploration of distinct subtypes of AMD.},
}
@article {pmid40577636,
year = {2025},
author = {Kato, N and Haruta, M and Matsuo, Y and Dake, S and Kojima, Y and Arai, R and Sato, K and Furushima, K and Yoshida, S},
title = {COMPARISON OF OCULAR BLOOD FLOW CHANGES AT 30 MINUTES AFTER INTRAVITREAL INJECTION OF FARICIMAB, BROLUCIZUMAB, AND AFLIBERCEPT 2 mg FOR NEOVASCULAR AGE-RELATED MACULAR.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {11},
pages = {2042-2048},
doi = {10.1097/IAE.0000000000004561},
pmid = {40577636},
issn = {1539-2864},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Regional Blood Flow/physiology/drug effects ; Aged, 80 and over ; *Choroid/blood supply ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Visual Acuity ; Fluorescein Angiography ; *Optic Disk/blood supply ; Tomography, Optical Coherence ; Blood Flow Velocity/physiology ; Time Factors ; Fundus Oculi ; Follow-Up Studies ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To investigate ocular blood flow before and 30 minutes postinjection of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration and to compare the reduction rates of ocular blood flow among three groups: intravitreal faricimab injections (faricimab-treated), intravitreal brolucizumab injections (brolucizumab-treated), and intravitreal aflibercept 2 mg injections (aflibercept-treated).<br><br>METHODS: This retrospective observational case series included 45 eyes of 45 Japanese patients with neovascular age-related macular degeneration treated with faricimab, brolucizumab, or aflibercept 2 mg. Ocular blood flow at the optic nerve head (ONH MV) and the choroid (choroid mean blur rate) was analyzed before and 30 minutes after injections using laser speckle flowgraphy.<br><br>RESULTS: The mean optic nerve head MV and choroid mean blur rate decreased significantly 30 minutes postinjection by 12.0% &#xb1; 15.3% and 9.7% &#xb1; 8.8% in the faricimab-treated group, 9.5% &#xb1; 7.9% and 18.2% &#xb1; 12.9% in the brolucizumab-treated group, and 10.4% &#xb1; 11.9% and 6.0% &#xb1; 7.7% in the aflibercept-treated group. There were no significant differences in the reduction rates of optic nerve head MV among the three groups. However, the brolucizumab-treated group showed a greater reduction in choroid mean blur rate than the aflibercept-treated group (faricimab vs. brolucizumab: P = 0.161; faricimab vs. aflibercept: P = 0.631; brolucizumab vs. aflibercept: P = 0.027).<br><br>CONCLUSION: Ocular blood flow significantly decreased 30 minutes postinjection in faricimab-treated, brolucizumab-treated, or aflibercept-treated eyes with neovascular age-related macular degeneration. Brolucizumab-treated eyes showed a significantly greater reduction in choroidal blood flow than aflibercept-treated eyes.},
}
@article {pmid40577635,
year = {2025},
author = {Oka, A and Murakami, R and Machida, A and Hirata, Y and Miyagi, S and Kurihara, J and Oishi, A},
title = {PACHYCHOROID NEITHER PROMOTES NOR INHIBITS THE FORMATION OF FIBROSIS IN MACULAR NEOVASCULARIZATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {11},
pages = {2035-2041},
doi = {10.1097/IAE.0000000000004569},
pmid = {40577635},
issn = {1539-2864},
support = {no. 22K09793//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Male ; Female ; Aged ; Fibrosis ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; Retrospective Studies ; Fluorescein Angiography/methods ; *Choroid/pathology ; Visual Acuity ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Neovascularization/drug therapy/diagnosis ; Middle Aged ; Intravitreal Injections ; Fundus Oculi ; Aged, 80 and over ; *Choroidal Neovascularization/drug therapy/diagnosis ; Ranibizumab ; *Macula Lutea/pathology ; },
abstract = {PURPOSE: Subretinal fibrosis is a major cause of vision loss during macular neovascularization (MNV) treatment. This study investigated the effect of the pachychoroid phenotype on subretinal fibrosis development after antivascular endothelial growth factor therapy for MNV.<br><br>METHODS: A total of 107 eyes from 107 patients (63 males, 44 females; mean age 72.9 &#xb1; 8.8 years) treated with antivascular endothelial growth factor therapy for MNV and followed for at least 4 years were included. Univariate and multivariate analyses identified factors associated with subretinal fibrosis at 4 years.<br><br>RESULTS: Subretinal fibrosis developed in 18 eyes (16.8%) after 4 years of therapy. Fibrosis occurred more frequently in eyes with type 2 MNV (44.4%) and subretinal hemorrhage (88.9%) (P = 0.026 and 0.001, respectively). The incidence of fibrosis did not differ between eyes with and without pachychoroid features (14.8% vs. 18.9%, P = 0.614). Logistic regression identified subretinal hemorrhage, type 2 MNV, and taller pigment epithelium detachment as significant factors (P = 0.0424, 0.0193, and 0.0149, respectively).<br><br>CONCLUSION: In addition to subretinal hemorrhage and type 2 MNV, taller pigment epithelium detachment was associated with subretinal fibrosis. The pachychoroid phenotype was neither a promoting nor protective factor for fibrosis.},
}
@article {pmid40577617,
year = {2025},
author = {Hsu, J and Cappellani, F and Nguyen, MK and Momenaei, B and Regillo, CD and Xu, D and Garg, SJ and Kuriyan, AE and Chiang, A and Ho, AC},
title = {ATROPHY GROWTH RATES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION COMPARED WITH FELLOW EYES WITH DRY AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {10},
pages = {1833-1841},
doi = {10.1097/IAE.0000000000004567},
pmid = {40577617},
issn = {1539-2864},
support = {//J. Arch McNamara, MD Fund for Retina Research and Education, Philadelphia, PA/ ; },
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; *Geographic Atrophy/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Disease Progression ; Intravitreal Injections ; Fluorescein Angiography/methods ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Atrophy ; Middle Aged ; Ranibizumab/administration &amp; dosage ; *Macula Lutea/pathology ; Fundus Oculi ; },
abstract = {PURPOSE: To study the natural history and anatomical characteristics of geographic atrophy in eyes with dry age-related macular degeneration (dAMD) compared with fellow eyes with macular atrophy and concurrent neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor injections.<br><br>METHODS: This is a single-center, retrospective chart review. Data were recorded at two time points (#1 and #2) one year apart. Two independent graders reviewed the images to measure atrophy area and grade it based on the Consensus on Atrophy Meeting group criteria. Difference in atrophy area between the two time points was calculated. A square root transformation was also performed to report the change in atrophy progression.<br><br>RESULTS: Two hundred eight eyes of 104 patients were included: 104 eyes had dAMD and 104 fellow eyes had nAMD. The mean (SD) atrophy area was 14.05 (9.96) mm 2 in dAMD eyes and 14.14 (9.26) mm 2 in nAMD eyes (P = 0.95) at time point #1, and 16.92 (10.83) mm 2 in dAMD eyes and 17.35 (11.03) mm 2 in nAMD eyes (P = 0.78) at time point #2. The mean (SD) atrophy growth rate was 3.08 (2.52) mm 2 /year in the nAMD eyes and 2.77 (1.88) mm 2 /year in the dAMD eyes (P = 0.32). Using the square root transformation, the growth rates were 0.40 (0.24) mm/year in nAMD and 0.38 (0.22) mm/year in dAMD (P = 0.55).<br><br>CONCLUSION: Geographic atrophy in eyes with dAMD and macular atrophy in fellow eyes with nAMD exhibit similar growth rates, suggesting a high degree of concordance and potentially a similar mechanism of atrophy development and progression.},
}
@article {pmid40576882,
year = {2025},
author = {Hikichi, T and Kurabe, H and Notoya, A and Oguro, Y and Hirano, M and Doi, Y},
title = {Short‑term outcomes of switching to faricimab for macular edema secondary to retinal vein occlusion.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {6},
pages = {918-925},
pmid = {40576882},
issn = {1613-2246},
mesh = {Humans ; *Retinal Vein Occlusion/complications/diagnosis/drug therapy ; Retrospective Studies ; *Macular Edema/drug therapy/etiology/diagnosis ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Tomography, Optical Coherence ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Middle Aged ; *Drug Substitution ; Treatment Outcome ; Fluorescein Angiography ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Aged, 80 and over ; Macula Lutea/pathology ; Antibodies, Bispecific ; },
abstract = {PURPOSE: This study evaluated the anatomical and functional outcomes in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) who were switched from conventional anti-vascular endothelial growth factor (VEGF) agents to faricimab.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: This study included 42 eyes from 42 patients treated at Hikichi Eye Clinic between April and August 2024. All patients had relapsed ME despite prior treatment with aflibercept and were switched to intravitreal faricimab (6.0 mg). The primary endpoints included best-corrected visual acuity (BCVA), central foveal thickness (CFT), and intravitreal injection intervals over six months.<br><br>RESULTS: The mean (&#xb1; standard error) CFT significantly decreased from 356 &#xb1; 23 &#x3bc;m to 214 &#xb1; 3 &#x3bc;m at one month (p < 0.01) and remained stable at the final visit (205 &#xb1; 4 &#x3bc;m). Logarithm of the minimum angle of resolution (logMAR) BCVA improved from 0.16 &#xb1; 0.03 to 0.04 &#xb1; 0.03 at one month (p < 0.01) and remained at 0.02 &#xb1; 0.02 at the final visit. The mean injection interval was significantly extended from 12.3 &#xb1; 0.4 weeks to 16.2 &#xb1; 0.5 weeks (p < 0.01).<br><br>CONCLUSION: Faricimab improved anatomical and functional outcomes while extending treatment intervals in ME secondary to RVO. Further large-scale, prospective, and long-term follow-up studies are needed to confirm these findings.},
}
@article {pmid40576874,
year = {2025},
author = {Sun, X and Li, Y and Song, Z and Ma, X and Yan, H and Yu, S and Zhang, J and Wu, Y and Huang, Z and Wang, H and Bai, T and Hu, J and Tan, J and Lin, X},
title = {Challenges and Opportunities for Improving Management of Patients with nAMD and DME in China: Insights from a Global Survey on Anti-VEGF Therapy.},
journal = {Advances in therapy},
volume = {42},
number = {9},
pages = {4390-4402},
pmid = {40576874},
issn = {1865-8652},
mesh = {Humans ; China ; *Angiogenesis Inhibitors/therapeutic use/economics/administration &amp; dosage ; *Macular Edema/drug therapy ; Male ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Female ; *Diabetic Retinopathy/drug therapy ; Surveys and Questionnaires ; Aged ; Middle Aged ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Practice Patterns, Physicians' ; },
abstract = {INTRODUCTION: This survey investigated the challenges and opportunities during anti-vascular endothelial growth factor (VEGF) therapy in Chinese patients.<br><br>METHODS: The survey was conducted in six&#xa0;hospitals from different regions in China, as part of the Barometer global survey. Paper-based optical mark recognition (OMR) questionnaires were answered by 498 and 527 patients who had been diagnosed with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), respectively, and were currently receiving or had previously received anti-VEGF injections, and by physicians who prescribe and/or administer anti-VEGF injections for the treatment of nAMD/DME. A total of 105 nAMD physicians and 105 DME physicians completed the questionnaire.<br><br>RESULTS: More than half of patients with DME (60.7%) and doctors (69.5%) identified long periods of waiting during the appointment as a challenge. Over 85% of physicians and 55% of patients identified the limitation on number of treatments covered by insurance plans as another main challenge. The main opportunities to improve patient care agreed upon by physicians and patients were the provision of financial assistance with drug/prescription costs and lifting of reimbursement restrictions (84.3-94.3%), less frequent appointments, longer time in between treatments without compromising vision (82.9-95.2%), and increasing predictability of the injection schedule (83.9-95.2%). Over 90% of doctors and patients agreed that more time for doctors to answer questions/concerns during each appointment is an important need to strengthen communication.<br><br>CONCLUSION: Lifting reimbursement limits, reducing appointments and extending the time between treatments without compromising vision, and increasing the time available to answer patient questions at each visit are key opportunities to improve patients' adherence and persistence for anti-VEGF therapy.},
}
@article {pmid40576434,
year = {2025},
author = {Swan, J and Toomey, CB and Bergstrand, M and Cuello, HA and Robie, J and Yu, H and Yuan, Y and Kooner, AS and Chen, X and Shaughnessy, J and Ram, S and Varki, A and Gagneux, P},
title = {The Sialome of the Retina, Alteration in Age-Related Macular Degeneration Pathology, and Potential Impacts on Complement Factor H.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {81},
pmid = {40576434},
issn = {1552-5783},
support = {R01 AI130684/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Complement Factor H/metabolism ; *Macular Degeneration/metabolism/pathology ; *Retina/metabolism/pathology ; Aged ; Retinal Pigment Epithelium/metabolism ; Aged, 80 and over ; Female ; Bruch Membrane/metabolism ; Male ; Middle Aged ; *N-Acetylneuraminic Acid/metabolism ; *Sialic Acids/metabolism ; },
abstract = {PURPOSE: Little is known about sialic acids of the human retina, despite their integral role in self /non-self-discrimination by complement factor H (FH), the alternative complement pathway inhibitor.<br><br>METHODS: A custom sialoglycan microarray was used to characterize the sialic acid-binding specificity of native FH or recombinant molecules where IgG Fc was fused to FH domains 16 to 20 (which contains a sialic acid-binding site), domains 6 and 7 (which contains a glycosaminoglycan-binding site), or the FH-related proteins (FHRs) 1 and 3. We analyzed macular and peripheral retinal tissue from postmortem ocular globes for the amount, type, and presentation (glycosidic linkage type) of sialic acid in individuals with age-related macular degeneration (AMD) and age-matched controls using fluorescent lectins and antibodies to detect sialic acid and endogenous FH. Released sialic acids from neural retina, retinal pigmented epithelium (RPE) cells, and the Bruch's membrane (BrM) were labeled with 1,2-diamino-4,5-methylenedioxybenzene-2HCl (DMB), separated and quantified by high-performance liquid chromatography (HPLC).<br><br>RESULTS: Both native FH and the recombinant FH domains 16 to 20 recognized Neu5Ac and Neu5Gc that is &#x3b1;2-3-linked to the underlying galactose. 4-O-Actylation of sialic acid and sulfation of GlcNAc did not inhibit binding. Different linkage types of sialic acid were localized at different layers of the retina. The greatest density of &#x3b1;2-3-sialic acid, which is the preferred ligand of FH, did not colocalize with endogenous FH. The level of sialic acids at the BrM/choroid interface of the macula and peripheral retina of individuals with AMD were significantly reduced.<br><br>CONCLUSIONS: The sialome of the human retina is altered in AMD. This may affect FH binding and, consequently, alternative complement pathway regulation.},
}
@article {pmid40575145,
year = {2025},
author = {Kammer, RL and Federici, R and Gormley, S},
title = {Topical Review: Clinical, Physiological, and Functional Benefits of Home-based Telerehabilitation with Occupational Therapists for Low Vision.},
journal = {International journal of telerehabilitation},
volume = {17},
number = {1},
pages = {6703},
pmid = {40575145},
issn = {1945-2020},
abstract = {For patients with low vision, rehabilitation enables the performance of daily activities and the acquisition of skills while enhancing quality of life, despite vision loss. Access to comprehensive low vision rehabilitation services, however, is often limited. The rise of telehealth during the COVID-19 pandemic has facilitated innovative delivery of healthcare, including telerehabilitation for low vision. This literature review was undertaken to evaluate the current evidence regarding telerehabilitation conducted by occupational therapists for patients with low vision. In this review, studies investigating the effects of new programs largely found significant improvements in outcomes. Results of a multicenter, randomized controlled trial found that reading ability significantly improved and results did not differ between therapies conducted through telerehabilitation or in-office. Additionally, studies surveying providers and patients regarding their sentiments about telehealth found that comfort level and overall satisfaction were similar between in-office visits and telerehabilitation.},
}
@article {pmid40573278,
year = {2025},
author = {Rusciano, D},
title = {A Personal Scientific Journey in Ophthalmology: Twenty-Five Years of Translating Research into Novel Therapies.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {6},
pages = {},
pmid = {40573278},
issn = {1424-8247},
abstract = {Ocular diseases including glaucoma, diabetic retinopathy and age-related macular degeneration represent a growing global health burden, with current treatments often providing only symptomatic relief. Through an integrated approach combining preclinical models, molecular biology, and clinical insights, this review synthesizes 25 years of my translational research to advance therapeutic strategies for these conditions. Key findings demonstrate the following: (1) the dual neuroprotective and intraocular pressure-lowering effects of natural compounds (EGCG, forskolin) in glaucoma models; (2) successful development of Uparant, a first-in-class peptide inhibitor of pathological angiogenesis with efficacy in retinal disease models; and (3) innovative drug delivery systems (melatonin nanomicelles, liposomal sprays) that enhance ocular bioavailability. Notably, some of these approaches have progressed to early-phase clinical trials, demonstrating translational potential. Significant challenges remain in optimizing sustained drug delivery and addressing the heterogeneity of ocular diseases through personalized approaches. Future directions include combinatorial therapies and the application of artificial intelligence for treatment optimization. Collectively, this work establishes a framework for developing multi-target therapies that address both the molecular mechanisms and clinical needs in ophthalmology.},
}
@article {pmid40572507,
year = {2025},
author = {Rykowska, I and Nowak, I and Nowak, R and Michałkiewicz, O},
title = {Biodegradable Contact Lenses for Targeted Ocular Drug Delivery: Recent Advances, Clinical Applications, and Translational Perspectives.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {12},
pages = {},
pmid = {40572507},
issn = {1420-3049},
mesh = {Humans ; *Drug Delivery Systems/methods ; *Contact Lenses ; Polymers/chemistry ; Ophthalmic Solutions/chemistry ; Administration, Ophthalmic ; Animals ; Drug Liberation ; Translational Research, Biomedical ; Dry Eye Syndromes/drug therapy ; },
abstract = {Ocular drug delivery presents a persistent clinical challenge due to the protective anatomical structure of the eye, physiological barriers such as reflex blinking, and continuous tear fluid turnover. These factors significantly limit the bioavailability of topically applied medications, reducing the therapeutic effectiveness of conventional formulations, such as eye drops, ointments, and suspensions, particularly in the management of chronic ocular disorders, including dry eye syndrome, diabetic retinopathy, and age-related macular degeneration. Drug-eluting contact lenses (DECLs) offer a promising alternative, enabling sustained, localized, and controlled drug release directly at the ocular surface. While several reviews have addressed contact lenses as drug delivery platforms, this work provides a distinct perspective by focusing specifically on biodegradable polymer-based systems. Emphasis is placed on recent advances in the design and fabrication of DECLs using natural and synthetic biodegradable polymers, which offer superior biocompatibility, customizable degradation kinetics, and the capacity for programmable drug release. This review discusses the selection criteria for polymer matrices, strategies for drug incorporation, and key factors influencing release profiles. Moreover, this study highlights innovative methodologies and therapeutic approaches that differentiate it from the existing literature, providing a timely and comprehensive resource for researchers developing next-generation polymeric ocular drug delivery systems.},
}
@article {pmid40571871,
year = {2025},
author = {Li, X and Ibrahim, KS and Baran, MR and Tchivelekete, GM and Zhou, X and Wu, Y and Reilly, J and Tan, Z and He, Z and Shu, X},
title = {Traditional Chinese Medicine, Ziyin-Mingmu Decoction, Regulates Cholesterol Metabolism, Oxidative Stress, Inflammation and Gut Microbiota in Age-related Macular Degeneration Models.},
journal = {Pharmaceutical research},
volume = {42},
number = {7},
pages = {1101-1118},
pmid = {40571871},
issn = {1573-904X},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Oxidative Stress/drug effects ; *Macular Degeneration/drug therapy/metabolism/microbiology/pathology ; *Cholesterol/metabolism ; Humans ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; Mice ; Inflammation/drug therapy/metabolism ; Disease Models, Animal ; Male ; Medicine, Chinese Traditional/methods ; Retinal Pigment Epithelium/drug effects/metabolism ; Antioxidants/pharmacology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the commonest cause of retinal disorders in the aged population. Ziyin-Mingmu decoction (ZD) has been widely used to treat AMD patients over thousands of years, however the underlying functional mechanisms of ZD are largely elusive. In this study, we aim to elucidate the therapeutic mechanisms of ZD in AMD models.<br><br>METHODS: An in vivo AMD mouse model and&#xa0;an in vitro AMD model were established. Cholesterol level in mouse tissues was measured. Expression of antioxidant genes and proinflammatory cytokines in mouse tissues and in human retinal pigment epithelial (RPE) cells were detected using biochemical approaches. Gut microbiota community and functional pathways were analysed using bioinformatics approach. Compounds in ZD were identified using HPLC/MS.<br><br>RESULTS: High fat diet (HFD)-fed mice had significantly higher levels of cholesterol in the retina, RPE, liver and serum, and markedly decreased expression of cholesterol metabolism-associated genes in those tissues, compared to mice fed with normal diet. Similarly, expression of antioxidant and inflammation genes was dysregulated in HFD-fed mouse tissues. ZD treatment reversed these HFD-induced pathological effects. HFD also altered the composition of cecum bacterial communities and associated metabolic pathways, which returned to control levels by ZD. In vitro assays showed that H2O2 significantly increased oxidative stress and enhanced expression of proinflammatory cytokines. Co-treatment with ZD significantly counteracted these changes. HPLC/MS identified 105 compound in water extracted ZD and most are polyphenols.<br><br>CONCLUSION: Our data suggests that protection of ZD against AMD is possibly through mitigating cholesterol level, oxidative stress and inflammation, and modulating gut microbiota by polyphenols.},
}
@article {pmid40570933,
year = {2025},
author = {Nanji, K and Grad, J and Hatamnejad, A and McKechnie, T and Phillips, M and Gemmy Cheung, CM and Patel, PJ and Marco, RD and Borrelli, E and Steel, DH and Sadda, SR and Wong, TY and Sivaprasad, S and Guymer, R and Wykoff, CC and Chaudhary, V},
title = {Baseline OCT Biomarkers Predicting Visual Outcomes in Neovascular Age-Related Macular Degeneration: A Meta-Analysis.},
journal = {Ophthalmology},
volume = {132},
number = {11},
pages = {1241-1252},
doi = {10.1016/j.ophtha.2025.06.018},
pmid = {40570933},
issn = {1549-4713},
mesh = {Humans ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Biomarkers ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Prognosis ; },
abstract = {TOPIC: To determine the effect estimates and certainty of evidence for baseline OCT biomarkers predicting visual acuity (VA) and changes in VA from baseline at 6, 12, and 24 months after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration.<br><br>CLINICAL RELEVANCE: Understanding the prognostic utility of biomarkers can improve treatment decisions.<br><br>METHODS: Results were reported in ETDRS letters. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines for prognostic studies informed certainty of evidence. Results were interpreted using a 5-letter minimally important difference.<br><br>RESULTS: Twenty-nine reports (8863 eyes) evaluating 80 biomarkers were included. Two biomarkers predicted better VA at 12 months with a low-certainty: the presence of an intact external limiting membrane (+14.0; 95% confidence interval [CI], +3.1 to +24.8) and the presence of an intact ellipsoid zone (+6.8; 95% CI, +2.8 to +10.8). Three biomarkers predicted worse VA at 12 months with a low certainty; the presence of intraretinal fluid (IRF; -5.6; 95% CI, -9.7 to -1.5), the presence of IRF in the foveal center point (-7.4; 95% CI, -10.1 to -4.7), and the presence of subretinal hyperreflective material (-8.7; 95% CI, -19.0 to 1.6). No other biomarker predicted an effect size that crossed the minimally important difference. However, noteworthy results occurred when interpreting biomarkers with statistically significant findings relative to a threshold of 0 letters and moderate certainty: the presence of a pigment epithelial detachment, geographic atrophy (GA), and both IRF and subretinal fluid (SRF) predicted reduced vision at 12 months. The presence of SRF predicted a positive change in VA at 12 months. The absence of a posterior vitreous detachment predicted a negative change in VA at 12 months. Finally, the presence of IRF in the central 1 mm, retinal pigment epithelial elevation, and GA predicted negative changes in VA at 24 months.<br><br>DISCUSSION: With low-certainty evidence, the baseline presence of an intact external limiting membrane and ellipsoid zone predicted better VA at 12 months, and the presence of IRF, IRF in the foveal center point, and subretinal hyperreflective material predicted worse VA at 12 months. Improved standardization in biomarker classification and control of confounding variables is needed.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40570232,
year = {2025},
author = {Zhang, X and Huang, Y and Ma, M and Zhou, C and Jiang, Y and Zhang, Z and Zhu, X and Li, C and Xu, X and Fan, Y and Han, C and Zheng, Z and Zhao, S},
title = {Childhood obesity directly increases age-related macular degeneration risk: the role of physiobiological and immune-metabolic function.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04164},
pmid = {40570232},
issn = {2047-2986},
mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; *Pediatric Obesity/epidemiology/complications ; Child ; Female ; Male ; Body Mass Index ; Middle Aged ; Risk Factors ; Aged ; Adult ; Mendelian Randomization Analysis ; Incidence ; },
abstract = {BACKGROUND: Childhood obesity is a growing global concern and is associated with cardiometabolic comorbidities in adulthood. However, the association between childhood body size and age-related macular degeneration (AMD) in late life remains to be investigated. We aimed to explore the association between childhood obesity and incident AMD and the underlying anatomical and physiobiological mechanisms.<br><br>METHODS: We investigated the association between childhood body size and incident AMD using multivariable Cox regression models and its relation to retinal layer thickness using linear regression. We performed four-way decomposition mediation analyses to explore the underlying mechanism. Lastly, we used univariable Mendelian randomisation (UVMR) and multivariable Mendelian randomisation (MVMR) to evaluate and differentiate the causal effect of childhood and adulthood body mass index (BMI).<br><br>RESULTS: Over a median follow-up of 12.8 years, 5026 incident AMD cases occurred among 487&#x2009;009 participants. Plumper childhood body size at age 10 conferred independent risk to incident AMD in later life (adjusted hazards ratio (aHR)&#x2009;=&#x2009;1.13; 95% confidence interval (CI)&#x2009;=&#x2009;1.03, 1.24, P&#x2009;=&#x2009;0.007) and was associated with photoreceptor outer segment layer thinning. Adulthood BMI mediated the association between childhood plumper body size and incident AMD (pure indirect effect&#x2009;=&#x2009;33%; 95% CI&#x2009;=&#x2009;9.9, 56.9, P&#x2009;=&#x2009;0.05). Mediation analysis of adulthood physiobiological and immuno-metabolic function showed that 17 peripheral biomarkers of 7 categories significantly mediated the aforementioned pathway, with HbA1c and cystatin C showing the two largest effects. Mendelian randomisation suggested a potential causal association between childhood BMI and AMD (UVMR inverse variance weighted (IVW) odd ratio (OR)&#x2009;=&#x2009;1.50; 95% CI&#x2009;=&#x2009;1.09, 2.08, P&#x2009;=&#x2009;0.013), independent of adulthood BMI (MVMR adulthood BMI-adjusted IVW OR&#x2009;=&#x2009;1.29; 95% CI&#x2009;=&#x2009;1.03, 1.61, P&#x2009;=&#x2009;0.024).<br><br>CONCLUSIONS: Childhood obesity may be a causal risk factor for incident AMD in later life, partially mediated by persistent obesity and physiobiological memory. Prevention of retinal degenerative diseases should therefore begin in childhood, whereby children should be encouraged and supported to maintain a normal body size.},
}
@article {pmid40569499,
year = {2025},
author = {Lu, X and Kataoka, K and Kumagai, M and Nochi, Y and Yamamoto, A and Ko, R and Okada, AA},
title = {Comparison of intraocular pressure elevation following intravitreal injection of 70 µl aflibercept 8 mg.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {6},
pages = {926-931},
pmid = {40569499},
issn = {1613-2246},
mesh = {Humans ; Intravitreal Injections/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Intraocular Pressure/drug effects ; Retrospective Studies ; Male ; Female ; Aged ; *Ocular Hypertension/chemically induced/physiopathology/diagnosis ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Tonometry, Ocular ; Aged, 80 and over ; Dose-Response Relationship, Drug ; },
abstract = {PURPOSE: To assess the effect of increased injection volume on intraocular pressure (IOP) following intravitreal injections of aflibercept 8 mg (70 µl) compared to conventional anti-vascular endothelial growth factor drugs.<br><br>STUDY DESIGN: Retrospective observational study METHODS: This retrospective observational study included eyes treated with 50 &#xb5;l of either aflibercept 2 mg or faricimab 6 mg, followed by a switch to 70 &#xb5;l of aflibercept 8 mg. IOP was measured before and 30 minutes after intravitreal injections. IOP changes in treated and fellow eyes were analyzed, with potential associations examined between IOP changes and clinical parameters.<br><br>RESULTS: A total of 88 eyes from 85 patients were switched to aflibercept 8 mg during the study period. Due to incomplete data, 17 eyes from 15 patients were excluded, leaving 71 eyes from 70 patients for the analysis. IOP significantly increased from 13.2 &#xb1; 2.9 mmHg to 19.1&#xb1; 5.4 mmHg (P< 0.001) with 50 &#xb5;l injections and from 13.3 &#xb1; 2.9 mmHg to 19.8 &#xb1; 4.8 mmHg (P<0.001) with 70 &#xb5;l injections. The IOP increases were 6.0 &#xb1; 5.0 mmHg with 50 &#xb5;l injections and 6.5 &#xb1; 4.3 mmHg with 70 &#xb5;l injections, with no statistically significant difference (P = 0.20). An IOP exceeding 26 mmHg was observed in 6 eyes treated with 50 &#xb5;l injections and 10 eyes with 70 &#xb5;l injections, with no significant difference in IOP distribution between the volumes (P = 0.20).<br><br>CONCLUSION: There was no additional increase in IOP 30 minutes after intravitreal injections when switching from 50 &#xb5;l to 70 &#xb5;l volumes.},
}
@article {pmid40566556,
year = {2025},
author = {Musadiq, M and Musadiq, M and Latif, F and Ng, B and Azzopardi, M and Gilead, N and Needham, A and Chong, YJ},
title = {Early Real-World Outcomes of Switching to 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration in the United Kingdom.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
pmid = {40566556},
issn = {2075-1729},
abstract = {(1) Aim: To evaluate early real-world outcomes of switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) in the United Kingdom. (2) Methods: This retrospective, observational study included 59 eyes from 50 patients with treatment-refractory nAMD previously treated with multiple anti-vascular endothelial growth factor (anti-VEGF) agents. Eyes were switched to aflibercept 8 mg without loading doses and treated using a treat-and-extend regimen. Functional, anatomical, and safety outcomes were evaluated over a mean (SD) follow-up of 33.5 (10.4) weeks. (3) Results: The mean (SD) age was 80.2 (6.3) years, and 28 (56.0%) of 50 patients were male. At baseline, the mean (SD) best corrected visual acuity (BCVA) was 66.0 (14.4) letters, with 33 (55.9%) eyes achieving ≥70 letters. The mean (SD) baseline central subfield thickness (CST) was 367.2 (100.7) µm. Prior to switching to aflibercept 8 mg, the mean (SD) number of injections for each eye was 26.9 (19.0), with the most recent mean (SD) treatment interval of 7.7 (1.7) weeks. Switching to aflibercept 8 mg resulted in extension of the mean (SD) injection interval from 7.7 (1.7) weeks to 8.7 (2.2) weeks (p < 0.01). BCVA and CST remained stable, with a significant reduction in pigment epithelial detachment (PED) height (232.5 µm to 211.6 µm, p < 0.01). No serious ocular adverse events or intraocular pressure (IOP) elevations requiring treatment were reported. (4) Conclusion: Aflibercept 8 mg demonstrated early treatment durability, anatomical benefit, and a favourable short-term safety profile in eyes with treatment-refractory nAMD. Further prospective studies are warranted.},
}
@article {pmid40565902,
year = {2025},
author = {Luttrull, JK and Sinclair, SH and Kozak, I},
title = {Laser Prophylaxis for Dry Age-Related Macular Degeneration: Current Evidence.},
journal = {Journal of clinical medicine},
volume = {14},
number = {12},
pages = {},
pmid = {40565902},
issn = {2077-0383},
abstract = {PURPOSE: To review the role of prophylactic panmacular laser treatment for age-related macular degeneration (AMD).<br><br>METHOD: A narrative review of studies employing laser treatment for non-exudative ("dry") AMD listed in the PubMed database.<br><br>RESULTS: In multiple published studies, macular laser treatment that causes laser-induced retinal damage (LIRD) has shown either no overall benefit or has accelerated disease progression and vision loss in eyes with dry AMD, particularly in high-risk eyes with more severe pre-treatment disease. Conversely, other studies, including randomized and matched propensity-scored real-world-data (RWD) clinical studies, indicate that avoidance of LIRD may allow laser to be used safely and effectively to prevent vision loss from AMD by slowing disease progression and preventing neovascular conversion without adverse treatment effects, benefiting the highest-risk eyes most.<br><br>CONCLUSIONS: AMD is the leading cause of irreversible vision loss worldwide. Current evidence suggests that laser prophylaxis for dry AMD may hold great promise in preventing age-related vision loss. More studies, especially prospective clinical trials, from more investigators, are needed. If current evidence is confirmed, laser prophylaxis would rise to a preeminent position as the safest, most effective, and most economical and accessible approach to reducing vision loss from AMD.},
}
@article {pmid40565365,
year = {2025},
author = {Lu, Z and Liu, S and Morales, MG and Whitlock, A and Ramkumar, R and Ramkumar, HL},
title = {Retinal BMI1 Expression Preserves Photoreceptors in Sodium-Iodate-Induced Oxidative Stress Models.},
journal = {International journal of molecular sciences},
volume = {26},
number = {12},
pages = {},
pmid = {40565365},
issn = {1422-0067},
mesh = {Animals ; *Iodates/toxicity ; *Oxidative Stress/drug effects ; Mice ; *Polycomb Repressive Complex 1/genetics/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; *Retina/metabolism ; Electroretinography ; Mice, Inbred BALB C ; *Macular Degeneration/metabolism/genetics/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Tomography, Optical Coherence ; Dependovirus/genetics ; *Photoreceptor Cells, Vertebrate/metabolism ; Proto-Oncogene Proteins ; },
abstract = {Dry age-related macular degeneration (AMD) is a leading cause of vision loss in individuals over 50, yet no approved therapies exist for early or intermediate stages of the disease. Oxidative stress is a central driver of retinal degeneration in AMD, and sodium iodate (NaIO3)-induced injury serves as a well-characterized model of oxidative damage to the retinal pigment epithelium (RPE) and photoreceptors. BMI1, a poly-comb group protein involved in DNA repair, mitochondrial function, and cellular renewal, has emerged as a promising therapeutic target for retinal neuroprotection. We evaluated the efficacy of AAV-mediated BMI1 gene delivery in murine models using two administration routes: subretinal (SR) and suprachoroidal (SC). AAV5.BMI1 (1 × 10[9] vg/eye) was delivered SR in Balb/c mice and evaluated at 4 and 15 weeks post-injection. AAV8.BMI1 (5 × 10[9] or 1 × 10[10] vg/eye) was administered SC in C57BL/6 mice and assessed at 4 weeks. Control groups received BSS or AAV8.stuffer. Following NaIO3 exposure, retinal structure and function were analyzed by optical coherence tomography (OCT), electroretinography (ERG), histology, and molecular assays. SC delivery of AAV8.BMI1 achieved the highest levels of retinal BMI1 expression with no evidence of local or systemic toxicity. Treated eyes showed dose-dependent preservation of outer nuclear layer (ONL) thickness and significantly improved ERG responses indicating structural and functional protection. These findings support SC AAV.BMI1 gene therapy as a promising, minimally invasive, and translatable approach for early intervention in intermediate AMD.},
}
@article {pmid40565279,
year = {2025},
author = {Zibetti, C},
title = {Molecular Determinants of the Human Retinal Pigment Epithelium Cell Fate and Potential Pharmacogenomic Targets for Precision Medicine.},
journal = {International journal of molecular sciences},
volume = {26},
number = {12},
pages = {},
pmid = {40565279},
issn = {1422-0067},
support = {801133//Horizon H2020 MSCA CoFUND/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Precision Medicine/methods ; Epithelial-Mesenchymal Transition/genetics ; *Macular Degeneration/genetics/pathology/metabolism ; *Pharmacogenetics/methods ; Gene Regulatory Networks ; Transcription Factors/metabolism/genetics ; Cell Differentiation ; },
abstract = {Age-related macular degeneration (AMD) is a common cause of blindness worldwide, and it is projected to affect several million individuals by 2040. The human retinal pigment epithelium (hRPE) degenerates in dry AMD, prompting the need to develop stem cell therapies to replace the lost tissue by autologous transplantation and restore the visual function. Nevertheless, the molecular factors behind the hRPE cell fate determination have not been elucidated. Here we identify all molecular determinants of the hRPE cell fate identity by comprehensive and unbiased screening of predicted pioneer factors in the human genome: such TFs mediate coordinated transitions in chromatin accessibility and transcriptional outcome along three major stages of the hRPE genesis. Furthermore, we compile a complete census of all transcription factor-specific binding sites by footprinting analysis of the human epigenome along the RPE developmental trajectory. Gene regulatory networks were found to be involved in cellular responses to glucose and hypoxia, RPE nitrosative stress, type II epithelial-to-mesenchymal transition (EMT), and type III tumorigenic EMT, providing routes for therapeutic intervention on pleiotropic targets dysregulated in AMD, diabetic retinopathy, and cancer progression. Genome editing technologies may leverage this repository to devise functional screenings of regulatory elements and pharmacogenomic therapies in complex diseases, paving the way for strategies in precision medicine.},
}
@article {pmid40565235,
year = {2025},
author = {Pinelli, R and Lazzeri, G and Berti, C and Biagioni, F and Scaffidi, E and Ferrucci, M and Bumah, VV and Fornai, F},
title = {Retinal Autophagy for Sustaining Retinal Integrity as a Proof of Concept for Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {12},
pages = {},
pmid = {40565235},
issn = {1422-0067},
support = {RC 2024-2025//Ministero della Salute/ ; },
mesh = {*Autophagy ; *Macular Degeneration/pathology/metabolism ; Humans ; Animals ; *Retina/pathology/metabolism ; Retinal Pigment Epithelium/pathology/metabolism ; },
abstract = {Current evidence indicates that most types of autophagy represent a pivot in promoting retinal integrity. In healthy conditions, autophagy acts on multiple pathways, which are fundamental for the biochemistry and the fine structure of the retina. Autophagy is essential in granting visual processes. On the other hand, autophagy dysfunction characterizes several retinal disorders. This is mostly evident in age-related macular degeneration (AMD), which represents the most common degenerative disease leading to blindness. The involvement of autophagy in AMD is documented in vitro and in vivo experiments, and it is strongly suggested by clinical findings in humans. The present manuscript provides an overview of the specific types of autophagy, which prevail in the retina and their alterations in retinal degeneration with an emphasis on AMD. The dysfunction of specific autophagy steps was analyzed in relation to hallmarks of AMD pathology and symptoms. An extended session of the manuscript analyzes the connection between altered autophagy and cell pathology within retinal pigment epithelium, as well as the site and structure of extracellular aggregates named drusen. The significance of the drusen in relation to visual function is discussed in the light of the role of autophagy in regulating key steps of phototransduction.},
}
@article {pmid40564380,
year = {2025},
author = {Wu, J and Liu, X and Liu, Y and Su, W and Zhuo, Y},
title = {New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {6},
pages = {},
pmid = {40564380},
issn = {2306-5354},
support = {82171057//the National Natural Science Foundation of China/ ; BX20240440//China National Postdoctoral Program for Innovative Talents/ ; 202206080005//Science and Technology Program of Guangzhou, China/ ; },
abstract = {The process of aging exerts profound effects on various physiological systems, leading to the progression of chronic degenerative disorders and pathologies associated with advancing age. Cellular senescence plays a central role in the aging process and the onset of various eye conditions associated with advancing age, including age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, cataracts, and ocular surface disorders. The accumulation of senescent cells (SnCs) and their secretion of pro-inflammatory and tissue-remodeling factors, collectively known as the senescence-associated secretory phenotype (SASP), exacerbate chronic inflammation, oxidative stress, and tissue dysfunction, contributing to disease progression. This study is the first to systematically integrate the multifaceted mechanisms of cellular senescence in ocular diseases, revealing differential regulatory mechanisms of specific signaling pathways across different ocular pathologies, thereby providing novel insights into the pathogenesis of these disorders. SnC-targeted therapies such as senolytics, senomorphics, SASP modulators, mitochondrial-targeted antioxidants, and epigenetic reprogramming are emerging as regenerative therapies, demonstrating potent anti-inflammatory effects, restoration of normal tissue physiology, and successful regeneration of ocular defects in preclinical models and clinical trials, while slowing senescence-associated disease progression. This review not only summarizes the role of cellular senescence in ocular diseases but also delves into potential therapeutic strategies, particularly highlighting novel perspectives for root-cause-targeted therapies from the unique angle of senescence biology, which may pioneer new directions for the treatment of ocular pathologies.},
}
@article {pmid40563412,
year = {2025},
author = {Wang, N and Wang, Y and Zhang, L and Yang, W and Fu, S},
title = {Molecular Mechanisms of Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells: Implications for Age-Related Macular Degeneration (AMD) Progression.},
journal = {Biomolecules},
volume = {15},
number = {6},
pages = {},
pmid = {40563412},
issn = {2218-273X},
support = {22JR5RA914//the Construction Plan of the Gansu Province Natural Science Foundation Project/ ; 22ZSCQD02//Gansu Provincial Intellectual Property Program/ ; 23JRRA1490//Gansu Province Joint Research Fund Project/ ; 2023YFC3503400//National Key R&amp;D program of China/ ; 2019-ZD-38//Lanzhou Municipal Science and Technology Development Guidance Plan Project/ ; },
mesh = {Humans ; *Epithelial-Mesenchymal Transition ; *Macular Degeneration/pathology/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; Disease Progression ; Animals ; Oxidative Stress ; Signal Transduction ; Epigenesis, Genetic ; Autophagy ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of irreversible blindness worldwide, represents a complex neurodegenerative disorder whose pathogenesis remains elusive. At the core of AMD pathophysiology lies the retinal pigment epithelium (RPE), whose epithelial-mesenchymal transition (EMT) has emerged as a critical pathological mechanism driving disease progression. This transformative process, characterized by RPE cell dedifferentiation and subsequent extracellular matrix remodeling, is orchestrated through a sophisticated network of molecular interactions and cellular signaling cascades. Our review provides a comprehensive analysis of the molecular landscape underlying RPE EMT in AMD, with particular emphasis on seven interconnected pathological axes: (i) oxidative stress and mitochondrial dysfunction, (ii) hypoxia-inducible factor signaling, (iii) autophagic flux dysregulation, (iv) chronic inflammatory responses, (v) complement system overactivation, (vi) epigenetic regulation through microRNA networks, and (vii) key developmental signaling pathway reactivation. Furthermore, we evaluate emerging therapeutic strategies targeting EMT modulation, providing a comprehensive perspective on potential interventions to halt AMD progression. By integrating current mechanistic insights with therapeutic prospects, this review aims to bridge the gap between fundamental research and clinical translation in AMD management.},
}
@article {pmid40563363,
year = {2025},
author = {Boo, YC},
title = {Restoring Glutathione Homeostasis in Glycation-Related Eye Diseases: Mechanistic Insights and Therapeutic Interventions Beyond VEGF Inhibition.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {6},
pages = {},
pmid = {40563363},
issn = {2076-3921},
support = {RS-2024-00437643//Korea Health Industry Development Institute/Republic of Korea ; },
abstract = {Advanced glycation end-products (AGEs) and oxidative stress are recognized as central contributors to the pathogenesis of age-related or diabetic cataracts, diabetic retinopathy (DR), and age-related macular degeneration (AMD). These glycation-related diseases are characterized by impaired redox balance and decreased glutathione (GSH) levels. This review aims to examine the mechanistic links between AGEs and GSH depletion across ocular tissues by integrating in vitro, ex vivo, in vivo, and clinical studies relevant to this topic. The multiple levels of evidence highlight GSH homeostasis as both a biomarker and therapeutic target in glycation-related ocular disorders. Therapeutic strategies aimed at restoring GSH homeostasis under glycation stress are categorized into four mechanistic domains: (I) promoting GSH supply and synthesis, (II) enhancing GSH recycling, (III) mitigating glycation stress, and (IV) reducing oxidative and nitrosative stress. Most of these strategies have been explored via different approaches, and experimental findings with various interventions have shown promise in restoring GSH balance and mitigating AGE-induced damage. A pathological link between GSH depletion and vascular endothelial growth factor (VEGF) overexpression is observed in DR and wet AMD. GSH-centered interventions act upstream to modulate redox homeostasis while anti-VEGF therapies target downstream angiogenesis. This study supports the rationale for a dual-targeting strategy that combines redox-based interventions with VEGF inhibition in glycation-related ocular diseases.},
}
@article {pmid40563282,
year = {2025},
author = {Antemie, RG and Marc, G and Pele, R and Fizeșan, I and Creștin, IV and Borlan, R and Theodosis-Nobelos, P and Rekka, EA and Oniga, O and Crișan, O and Pîrnău, A and Vlase, L and Clichici, SV},
title = {Antioxidant Activity and Cytotoxicity Evaluation of New Catechol Hydrazinyl-Thiazole Derivatives as Potential Protectors in Retinal Degenerative Processes.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {6},
pages = {},
pmid = {40563282},
issn = {2076-3921},
support = {PCD 881/3/12 January 2022 and PCD 772/1/11 January 2023//"Iuliu Ha&#x163;ieganu" University of Medicine and Pharmacy Cluj-Napoca, Romania/ ; 27N/03.01.2023, component project code PN 23 24 01 05//"Nucleu" Program within the National Research Development and Innovation Plan 2022-2027, Romania, carried out with the support of MEC/ ; Installations and Special Objectives of National Interest (IOSIN), IZOSTAB//Romanian Ministry of Education and Research/ ; },
abstract = {Retinal degenerative processes such as age-related macular degeneration are at the center of many ongoing research studies, as their impact on the general population is significant, with severe visual impairment and even irreversible vision loss if left untreated. Currently, there are few efficient treatments available to stop or limit its progression. In the present paper, a molecular hybridization approach was employed to develop novel compounds that address this issue. By adding either 2-butenal or a β-ionone-derived residue to the hydrazone-catechol-thiazole scaffold, two compounds were designed and synthesized: 5a and 5b. After being characterized by mass spectrometry and nuclear magnetic resonance, and proving potent antioxidant activity in the in vitro assays, the cytotoxicity evaluation using the ARPE-19, BJ, and A549 cell lines revealed a surprisingly low-dose effect of 5a and the unexpected cytotoxic activity of 5b, despite its β-ionone moiety, known for its significant therapeutic properties.},
}
@article {pmid40563040,
year = {2025},
author = {Ahmed, F and Bhuiyan, MAN and Coskunuzer, B},
title = {Topo-CNN: Retinal Image Analysis with Topological Deep Learning.},
journal = {Journal of imaging informatics in medicine},
volume = {},
number = {},
pages = {},
pmid = {40563040},
issn = {2948-2933},
support = {P20 GM121307/GM/NIGMS NIH HHS/United States ; P20GM121307 to M.A.N.B/GF/NIH HHS/United States ; },
abstract = {The analysis of fundus images is vital for early detection of retinal diseases such as diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD), but traditional methods are resource-intensive. We propose an automated and interpretable diagnostic framework that leverages novel feature representations to improve performance. Our main contribution is a topological feature extraction technique based on Topological Data Analysis (TDA), which captures geometric and structural patterns in fundus images. These features are computationally efficient and interpretable. We integrate them with pretrained CNN features (e.g., ResNet-50) into a hybrid deep model, Topo-CNN, combining global image context with topological structure. We evaluate Topo-CNN on three benchmarks: APTOS (binary and five-class DR), ORIGA (Glaucoma), and IChallenge-AMD. Our model achieves 98.7% accuracy/98.9 AUC on binary DR, 95.5 AUC on five-class DR, 93.8% accuracy/93.6 AUC on AMD, and 82.3% accuracy/95.8 specificity on glaucoma. Ablation studies confirm the added value of topological features, and our Topo-CNN consistently outperforms existing methods across tasks.},
}
@article {pmid40560103,
year = {2025},
author = {Durmaz Engin, C and Beşenk, U and Özizmirliler, D and Selver, MA},
title = {Comparative Analysis of Automated vs. Expert-Designed Machine Learning Models in Age-Related Macular Degeneration Detection and Classification.},
journal = {Turkish journal of ophthalmology},
volume = {55},
number = {3},
pages = {120-126},
pmid = {40560103},
issn = {2149-8709},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Machine Learning ; *Macular Degeneration/diagnosis/classification ; Aged ; *Wet Macular Degeneration/diagnosis/classification ; },
abstract = {OBJECTIVES: To compare the effectiveness of expert-designed machine learning models and code-free automated machine learning (AutoML) models in classifying optical coherence tomography (OCT) images for detecting age-related macular degeneration (AMD) and distinguishing between its dry and wet forms.<br><br>MATERIALS AND METHODS: Custom models were developed by an artificial intelligence expert using the EfficientNet V2 architecture, while AutoML models were created by an ophthalmologist utilizing LobeAI with transfer learning via ResNet-50 V2. Both models were designed to differentiate normal OCT images from AMD and to also distinguish between dry and wet AMD. The models were trained and tested using an 80:20 split, with each diagnostic group containing 500 OCT images. Performance metrics, including sensitivity, specificity, accuracy, and F1 scores, were calculated and compared.<br><br>RESULTS: The expert-designed model achieved an overall accuracy of 99.67% for classifying all images, with F1 scores of 0.99 or higher across all binary class comparisons. In contrast, the AutoML model achieved an overall accuracy of 89.00%, with F1 scores ranging from 0.86 to 0.90 in binary comparisons. Notably lower recall was observed for dry AMD vs. normal (0.85) in the AutoML model, indicating challenges in correctly identifying dry AMD.<br><br>CONCLUSION: While the AutoML models demonstrated acceptable performance in identifying and classifying AMD cases, the expert-designed models significantly outperformed them. The use of advanced neural network architectures and rigorous optimization in the expert-developed models underscores the continued necessity of expert involvement in the development of high-precision diagnostic tools for medical image classification.},
}
@article {pmid40559108,
year = {2025},
author = {Grün, M and Rothaus, K and Ziegler, M and Lommatzsch, A and Lange, C and Faatz, H},
title = {Morphology of Macular Neovascularization in Age-Related Macular Degeneration Influences Treatment Requirement and Visual Outcome After 1 Year.},
journal = {Journal of personalized medicine},
volume = {15},
number = {6},
pages = {},
pmid = {40559108},
issn = {2075-4426},
support = {//Voltmann Foundation/ ; },
abstract = {Background/Objectives: To evaluate the potential of Optical Coherence Tomography (OCT) and OCT angiography parameters in predicting treatment requirements and visual outcomes after one year in therapy-naïve eyes with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study of 96 therapy-naïve eyes newly diagnosed with nAMD was carried out. All eyes received baseline OCT and OCTA. Follow-up OCT after initial upload was then carried out, involving three intravitreal injections (IVIs) with anti-Vascular Endothelial Growth Factor (anti-VEGF) at four-week intervals. OCT parameters, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and central retinal thickness (CRT), were assessed qualitatively and quantitatively. Macular Neovascularization (MNV) morphology at baseline was described in terms of area, total vessel length, flow density, and fractal dimension. OCT and OCTA parameters were correlated with best corrected visual acuity (BCVA) and number of administered IVIs after 1 year of treatment. Results: Eyes with persistent subretinal fluid (SRF) or both intraretinal fluid (IRF) and SRF after upload showed a significantly higher need for IVIs (p < 0.01). Also, pigment epithelium detachment (PED) presence at baseline (p < 0.05), PED height at baseline (p < 0.01), PED presence after upload (p < 0.01), and PED height after upload (p < 0.01) were each correlated with a greater number of IVIs. Decrease in PED height during upload was accompanied by a lower number of IVIs (p < 0.01). All the aforementioned parameters had no influence on BCVA after 1 year (p > 0.05). Baseline central retinal thickness (CRT) was linked to worse BCVA at 12 months (p < 0.05), but not the number of IVIs. Follow-up CRT correlated with worse BCVA (p < 0.01) and more IVIs (p < 0.01), while CRT decrease was associated with better BCVA (p < 0.05) and fewer IVIs (p < 0.01) at 1 year. In OCTA, area and total vessel length of MNVs were correlated with BCVA after 1 year (p < 0.01) but had no influence on number of IVIs (p > 0.05). Flow density had no influence on either outcome parameter (p > 0.05). Fractal dimension was associated with BCVA (p < 0.01) and number of IVIs (p < 0.05) after 1 year. Conclusions: MNV area, vessel length, and fractal dimension in OCTA, along with fluid distribution in OCT at baseline and after follow-up, may serve as indicators of treatment needs and visual outcomes after one year. Further studies with longer observation periods and the use of deep learning models are needed to improve analyses and to verify the applicability of these findings to clinical practice.},
}
@article {pmid40558564,
year = {2025},
author = {Bisen, S and Singh, NK},
title = {Implications of Fatty Acids for Age-Related Macular Degeneration: Evidence and Recommendations.},
journal = {Cells},
volume = {14},
number = {12},
pages = {},
pmid = {40558564},
issn = {2073-4409},
support = {R01 EY029709/EY/NEI NIH HHS/United States ; EY029709//National Eye Institute, NIH/ ; },
mesh = {Humans ; *Macular Degeneration/metabolism/pathology/diet therapy ; *Fatty Acids/metabolism/therapeutic use ; Fatty Acids, Omega-3 ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is an ocular pathology in humans characterized by the buildup of lipid-rich extracellular deposits, which leads to retinal degeneration. In recent years, considerable effort has been made to observe the effect of dietary fatty acids on oxidative stress and inflammation. In continuation of this, much effort has been made to study the effect of dietary fatty acids on the pathogenesis of AMD. Although studies have shown that dietary fatty acids are effective against few forms of AMD, particularly wet AMD or neovascular AMD, no dietary lipids have shown any conclusive results for dry AMD or geographic AMD. It is therefore important to look for new lipids and lipoproteins that can be helpful in treating various stages of AMD. This article reviews the impact of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) on retinal health and the progression of AMD. Furthermore, this manuscript discusses all studies investigating the implications of fatty acids on AMD, which may be beneficial for future treatment strategies and dietary guidelines related to it. In conclusion, studies suggest that omega-3 PUFAs, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), might provide protection against AMD, highlighting the necessity for additional clinical trials to evaluate their efficacy in the prevention and treatment of AMD.},
}
@article {pmid40558523,
year = {2025},
author = {Muraleva, NA and Tikhonov, DI and Zhdankina, AA and Plotnikov, MB and Khlebnikov, AI and Logvinov, SV and Kolosova, NG},
title = {Alterations of JNK Signaling Pathway Activity in the Rat Retina: Effects of Age, Age-Related Macular Degeneration-like Pathology, and a JNK Inhibitor (IQ-1S).},
journal = {Cells},
volume = {14},
number = {12},
pages = {},
pmid = {40558523},
issn = {2073-4409},
support = {24-25-00030//Russian Science Foundation/ ; },
mesh = {Animals ; *Macular Degeneration/pathology/drug therapy/metabolism ; *Retina/pathology/drug effects/metabolism ; Rats, Wistar ; *MAP Kinase Signaling System/drug effects ; Rats ; *Aging/pathology/metabolism ; Male ; *Quinoxalines/pharmacology ; *Protein Kinase Inhibitors/pharmacology ; *Oximes/pharmacology ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. AMD development is associated with inflammation, oxidative stress, and a progressive proteostasis imbalance, in whose regulation, c-Jun N-terminal kinases (JNKs) play a crucial role. JNK inhibition is being discussed as a new way to prevent and treat AMD, but there are no data on JNK signaling in the retina and its changes with age and with AMD development. Here, for the first time, we assessed JNK-signaling activity in the retina and did not detect its age-related changes in healthy Wistar rats. By contrast, manifestation and progression of the AMD-like pathology in OXYS rats occurred simultaneously with JNK pathway activation. We also confirmed that selective JNK3 inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S) can suppress neurodegenerative changes in the OXYS rat retina. Its effects were prevention of the destructive changes in retinal synapses and the suppression of the JNK signaling pathway activity during active progression of AMD signs in OXYS rats.},
}
@article {pmid40557781,
year = {2025},
author = {Trinh, M and Cheung, R and Nam, J and Ng, D and Nivison-Smith, L and Ly, A},
title = {High risk does not guarantee high accuracy-Evaluating the prognostic accuracy of OCT biomarkers for predicting late AMD.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {6},
pages = {1293-1301},
pmid = {40557781},
issn = {1475-1313},
support = {1174385//NHMRC/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Prognosis ; Biomarkers ; Aged ; ROC Curve ; *Macular Degeneration/diagnosis ; *Retinal Pigment Epithelium/pathology ; Disease Progression ; Middle Aged ; Aged, 80 and over ; Follow-Up Studies ; },
abstract = {PURPOSE: The translation of high-risk biomarkers into accurate predictions of late age-related macular degeneration (AMD) may be limited by biomarker prevalence, subjective identification and competing risks from concurrent biomarkers. This study evaluates the prognostic performance of key optical coherence tomography (OCT) biomarkers for progression to late AMD, with colour fundus photography (CFP) as the reference standard.<br><br>METHODS: This retrospective study included 78 single eyes with intermediate AMD, propensity-score matched by age and sex between converters and non-converters to late AMD. Ten OCT biomarkers empirically derived from recent meta-analysis, alongside CFP biomarkers of large drusen and pigmentary abnormality, were independently graded by three clinician-researchers. Biomarkers' associated risk (odds ratios) and prognostic performance (area under the receiver operating characteristic curve (AUC), sensitivity, specificity) were evaluated for predicting late AMD.<br><br>RESULTS: The adjusted risk was highest for OCT-detected nascent geographic atrophy, shallow irregular retinal pigment epithelium (RPE) elevations, drusenoid pigment epithelium detachment and RPE reflective abnormality (odds ratios, 6.66 [1.32, 42.71] to 28.27 [2.44, 545.3], p&#x2009;<&#x2009;0.05). However, CFP-detected pigmentary abnormalities demonstrated the highest individual prognostic accuracy (77.69 [68.11, 87.27]% AUC, p&#x2009;<&#x2009;0.0001), with excellent sensitivity (92.31%) but moderate specificity (63.08%). Adding at least three OCT biomarkers was required to improve prognostic performance significantly (91.01 [84.66, 97.36]%, p&#x2009;<&#x2009;0.0001), and at least eight additional biomarkers to yield both excellent sensitivity (94.62%) and specificity (90.77%).<br><br>CONCLUSIONS: CFP-detected pigmentary abnormality remains a mainstay of clinical AMD prognostication, likely due to its higher prevalence and interpretability than high-risk OCT biomarkers. Integrating OCT biomarkers into clinical prognostic models is promising but complex and may require automated identification to aid efficiency.},
}
@article {pmid40555726,
year = {2025},
author = {Lee, TJ and Santeford, A and Pitts, KM and Ripoll, CV and Terao, R and Guo, Z and Ozcan, M and Kratky, D and Christoffersen, C and Javaheri, A and Apte, RS},
title = {Apolipoprotein M attenuates age-related macular degeneration phenotypes via sphingosine-1-phosphate signaling and lysosomal lipid catabolism.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5331},
pmid = {40555726},
issn = {2041-1723},
support = {P30 EY002687/EY/NEI NIH HHS/United States ; R01 EY019287/EY/NEI NIH HHS/United States ; R01 HL155344/HL/NHLBI NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; K08 HL138262/HL/NHLBI NIH HHS/United States ; },
mesh = {*Lysophospholipids/metabolism ; *Macular Degeneration/metabolism/pathology/genetics ; Animals ; *Sphingosine/analogs &amp; derivatives/metabolism ; *Apolipoproteins M/metabolism/genetics ; Humans ; *Lysosomes/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Signal Transduction ; *Lipid Metabolism ; Mice ; Mice, Knockout ; Male ; Female ; Phenotype ; Mice, Inbred C57BL ; Cholesterol/metabolism ; Aged ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in people over 50. AMD and cardiovascular disease share risk factors including age, impaired lipid metabolism, and extracellular lipid deposition. Because of its importance in age-related diseases, we hypothesize that apolipoprotein M (ApoM), a lipocalin that binds sphingosine-1-phosphate (S1P), might restore lipid homeostasis and retinal function in AMD. In support, we find that human patients with AMD demonstrate significantly reduced ApoM compared to controls. In mice with impaired retinal cholesterol efflux, ApoM improves retinal pigment epithelium (RPE) function and lipotoxicity in an S1P- and S1P receptor 3-dependent manner. Ultrastructural evidence of enhanced melanosome-lipid droplet interactions led us to hypothesize and demonstrate that ApoM-S1P signaling drives RPE-specific lysosomal lipid catabolism. RPE-specific knockout of lysosomal acid lipase recapitulates features of AMD. Our study defines a novel role for ApoM/S1P signaling in AMD driven by RPE lipotoxicity, mediated by cell-autonomous lysosomal lipid catabolism.},
}
@article {pmid40555396,
year = {2025},
author = {Han, YE and Choi, HI and Lee, J and Kim, YJ and Lee, JY and Sadda, SR and Yoon, YH},
title = {Geographic atrophy in Korean patients with dry age-related macular degeneration: incidence, phenotypes, and progression.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {6},
pages = {e925-e933},
doi = {10.1016/j.jcjo.2025.05.026},
pmid = {40555396},
issn = {1715-3360},
mesh = {Humans ; *Geographic Atrophy/epidemiology/diagnosis ; Incidence ; Disease Progression ; Male ; Female ; Retrospective Studies ; Republic of Korea/epidemiology ; Aged ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Phenotype ; Follow-Up Studies ; Fundus Oculi ; Middle Aged ; *Macular Degeneration/epidemiology/diagnosis ; *Visual Acuity ; Aged, 80 and over ; },
abstract = {OBJECTIVE: To evaluate the characteristics of geographic atrophy (GA) in Korean patients, including incidence, phenotypes, progression patterns, and factors associated with progression rates.<br><br>DESIGN: Retrospective longitudinal cohort study.<br><br>PARTICIPANTS: Korean patients with intermediate and advanced (prevalent GA) dry AMD, followed for &#x2265;3 years.<br><br>METHODS: GA incidence was defined as the percentage of new GA emerging from the intermediate dry AMD group during the follow-up. Baseline phenotypes were evaluated in the prevalent GA group at the initial visit using fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence (FAF). Progression patterns were assessed by growth rates (mm[2]/year and mm/year using square-root treansformation [SQRT]), and the centripetal growth direction (foveal involvement of extrafoveal lesions). Linear regression was used to identify factors associated with progression rates.<br><br>RESULTS: In intermediate dry AMD group (395 eyes/241 patients), GA incidence was 6.8%, while wet conversion was 14.4%, during 60.5 &#xb1; 13.5 months. In prevalent GA group (70 eyes/46 patients), the mean lesion size was 7.2 &#xb1; 7.1 mm[2] (2.4 &#xb1; 1.3 mm [SQRT]), with bilateral involvement in 68.6%, banded/diffuse FAF patterns in 81.4%, extrafoveal and multifocal locations in 51.4% and 84.3%, and drusen and reticular pseudodrusen in 87.1% and 34.3%. The progression rate was 2.0 &#xb1; 1.3 mm[2]/year (0.3 &#xb1; 0.2 mm/year [SQRT]), with 69.4% exhibiting centripetal direction during 61.2 &#xb1; 14.5 months. Large lesion size, banded/diffuse FAF patterns, and extrafoveal locations were positively associated with progression rates (p&#x202f;=&#x202f;0.006, 0.007, and 0.008).<br><br>CONCLUSIONS: The 5-year incidence of GA in Korean patients with intermediate dry AMD was 6.8%, approximately half of the rate of wet conversion. The mean GA progression rate was 2.0 mm[2]/year (0.3 mm/year [SQRT]). Risk factors for fast progression were banded/diffuse FAF patterns, extrafoveal locations, and large lesion size.},
}
@article {pmid40553257,
year = {2025},
author = {Mathivanan, I and Volker, E and Thyagarajan, K and Sivasubramanian, AT and Raju, K and Thangaraj, A},
title = {Age-Related Macular Degeneration: Therapeutic Strategies Based on Stem Cells.},
journal = {Stem cell reviews and reports},
volume = {21},
number = {7},
pages = {1867-1882},
pmid = {40553257},
issn = {2629-3277},
support = {BT/HRD/35/02/2006 dated 30/03/2021//Department of Biotechnology, Ministry of Science and Technology, India/ ; },
mesh = {Humans ; *Macular Degeneration/therapy/pathology ; *Stem Cell Transplantation/methods ; Retinal Pigment Epithelium/cytology ; Animals ; Induced Pluripotent Stem Cells/transplantation/cytology ; Cell Differentiation ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in developed countries, manifesting in two primary forms: neovascular (wet) AMD and non-neovascular (dry) AMD. Current treatments, such as anti-VEGF therapy, offer limited efficacy, particularly for dry AMD, highlighting the urgent need for alternative strategies. Advancements in contemporary treatment strategies for these eye conditions are a pressing medical concern. Stem cell-based therapies have emerged as a promising approach for retinal regeneration due to their capacity for self-renewal and differentiation into retinal cell types, including retinal pigment epithelial (RPE) cells and photoreceptors, two key cell populations damaged in AMD. Among the various sources, pluripotent stem cells such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) show significant potential in generating functional RPE cells and restoring retinal architecture and function. Preclinical and early clinical studies have demonstrated promising outcomes, including improved visual acuity and anatomical integration. However, challenges such as immune rejection, tumorigenicity, limited long-term integration, and ethical concerns continue to impede clinical translation. This review critically evaluates current stem cell-based therapeutic strategies for AMD, including advances in mesenchymal stem cells, retinal organoids, and combinatorial approaches with gene and nanotherapy. Furthermore, this review outlines the translational bottlenecks and future directions required to advance these therapies toward clinical application.},
}
@article {pmid40836983,
year = {2024},
author = {Dandamudi, M and McLoughlin, P and Behl, G and Coffey, L and Chauhan, A and Kent, D and Rani, S and Fitzhenry, L},
title = {Investigation of novel combination therapy for age-related macular degeneration on ARPE-19 cells.},
journal = {Frontiers in drug delivery},
volume = {4},
number = {},
pages = {1337686},
pmid = {40836983},
issn = {2674-0850},
abstract = {Age-related macular degeneration (AMD) is a multifactorial degenerative disease characterised by the gradual loss of central vision in individuals aged more than 50 years. There is currently no cure for this disease, but treatment can delay its progression. Consequently, there is an urgent need for the development of both new and cost-effective therapeutics. In this study, a novel combination of a corticosteroid and flavonoid was investigated on human retinal pigment epithelial cell lines to explore its potential pharmacological effect on AMD. Combination therapies, such as anti-VEGF (vascular endothelial growth factor) agents combined with photodynamic therapy and anti-VEGF agents in conjunction with corticosteroids, have been utilized previously and are known to be effective. However anti-VEGF injections are associated with serious side effects and are costly. Various disease conditions associated with AMD were stimulated on human retinal cells, which were then exposed to different concentrations of triamcinolone acetonide (TA) and quercetin (QCN) individually and in combination. This investigation aimed to assess their potential for the treatment of AMD. The combination of TA and QCN demonstrated a superior anti-inflammatory effect, as TA and QCN primarily act on different inflammatory signaling pathways. Furthermore, in terms of anti-VEGF activity, both drugs exert their effects through different mechanisms: QCN inhibits kinase pathways leading to the deactivation of VEGF receptors, whereas TA destabilises VEGF mRNA, resulting in increased suppression of VEGF-C with combination treatments. The anti-oxidant assay yielded similar outcomes, demonstrating a synergetic effect when treated with combination drugs. These findings collectively suggest TA and QCN as a promising combination therapy for targeting AMD with multiple pathological conditions.},
}
@article {pmid41307029,
year = {2024},
author = {Araki, T and Shimazawa, M and Nakamura, S and Otsu, W and Numata, Y and Sakata, M and Kabayama, K and Tsusaki, H and Hara, H},
title = {Macular white dot lesions with hyperreflective optical coherence tomography findings in cynomolgus and rhesus monkeys.},
journal = {Molecular vision},
volume = {30},
number = {},
pages = {219-233},
pmid = {41307029},
issn = {1090-0535},
mesh = {Animals ; *Tomography, Optical Coherence ; Macaca mulatta ; Female ; Macaca fascicularis ; Electroretinography ; *Macula Lutea/pathology/ultrastructure/physiopathology ; Retinal Pigment Epithelium/pathology/ultrastructure ; *Macular Degeneration/pathology/physiopathology ; },
abstract = {PURPOSE: We screened 28 female cynomolgus monkeys (CMs) and 25 female rhesus monkeys (RMs) for white dots (WDs) in the macula and detected several animals with WDs in colonies at the Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories (SNBL) facility. To determine the functional and morphological characteristics of WDs, we conducted ophthalmological and pathological examinations on these animals.<br><br>METHODS: Fundus examination, optical coherence tomography (OCT), and focal electroretinogram (f-ERG) were conducted for all animals. Histopathology and transmission electron microscopy were conducted for one representative adult CM with WDs.<br><br>RESULTS: In both CMs and RMs, individual differences were observed in the number of WDs in the macula (ranging from approximately 10 to 500 per eye). Hyperreflective granules were observed between the ellipsoid zone (EZ) and the retinal pigment epithelium (RPE) in OCT. Both CMs and RMs exhibited a significant increase in the thicknesses of the RPE and choroid in WD animals compared to their normal counterparts. In the f-ERG, significant decreases and/or tendencies toward decreases in amplitudes and increases in implicit times of both a- and b-waves were observed in animals with WDs. In pathology, diffuse vacuolization of the RPE cells with tiny granules was observed in the macula.<br><br>CONCLUSIONS: Based on the results of OCT and pathological examinations, it was suggested that animals with WDs can develop macular degeneration in the future. To assess their suitability as a model for precursor lesions of age-related macular degeneration, it is imperative to continue monitoring the animals used in the present study until they reach a more advanced age of approximately another 5-10 years.},
}
@article {pmid40552927,
year = {2025},
author = {Rudeen, KM and Maloney, CM and Lydon, KL and Teixeria, LBC and Mieler, WF and Kang-Mieler, JJ},
title = {Treatment Efficacy of a Dual Release of Aflibercept and Dexamethasone From a Single Hydrogel Drug Delivery System in a Rodent Model.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {6},
pages = {31},
pmid = {40552927},
issn = {2164-2591},
support = {R01 EY029298/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Dexamethasone/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Choroidal Neovascularization/drug therapy ; Disease Models, Animal ; *Drug Delivery Systems ; Tomography, Optical Coherence ; Fluorescein Angiography ; Rats ; Hydrogels ; Intravitreal Injections ; Electroretinography ; Intraocular Pressure/drug effects ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of vision loss for the elderly population. Wet AMD, which accounts for approximately 15% of AMD cases, is characterized by abnormal blood vessel growth from the choroid into the subretinal space. Although intravitreal anti-vascular endothelial growth factor (VEGF) agents have become the standard of care for wet AMD, there is a growing subset of patients who do not fully respond to monotherapy anti-VEGF treatment. In previously published reports, corticosteroids have shown improvements in treatment efficacy when administered with anti-VEGF in a subset of non-responders to anti-VEGF monotherapy.<br><br>METHODS: A combination dexamethasone and aflibercept drug delivery system (Combo-DDS) was evaluated in a laser-induced rodent model of choroidal neovascularization (CNV). Longitudinal monitoring was done through week 22 using fluorescein angiography (FA) and spectral domain optical coherence tomography (SD-OCT). Multi-Otsu thresholding was used to quantify the lesion area based on late-phase FA images. In addition, preliminary safety and biocompatibility of the Combo-DDS were evaluated by intraocular pressure (IOP) measurements, electroretinogram (ERG), and histology (n = 6 eyes/group).<br><br>RESULTS: In the laser-induced CNV model, CNV lesions (n = 28-36 lesions/group) were monitored longitudinally. Combo-DDS showed a regression in lesion size starting at week 2 that continued through the end of study. IOP, ERG, and histology showed preliminary safety and biocompatibility of the Combo-DDS.<br><br>CONCLUSIONS: This study demonstrated that Combo-DDS maintained treatment efficacy in a laser-induced CNV rodent model for 6 months.<br><br>TRANSLATIONAL RELEVANCE: The Combo-DDS shows the potential to eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for non-responders to anti-VEGF monotherapy.},
}
@article {pmid40552706,
year = {2025},
author = {Weissenbacher, LM and Schmidt, R and Vécsei-Marlovits, PV and Weingessel, B},
title = {Comparative treatment burden of intravitreal injection versus visit frequency in patients with exudative age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {103},
number = {7},
pages = {e533-e535},
doi = {10.1111/aos.17538},
pmid = {40552706},
issn = {1755-3768},
}
@article {pmid40551979,
year = {2025},
author = {Zhou, J and Zhao, D and Niu, S and Meng, W and Chen, Z and Li, H and Liu, Y and Zou, L and Li, W},
title = {RGD-Functionalized Ginsenoside Rg3 Liposomes for Alleviating Oxidative Stress and Choroidal Neovascularization in Age-Related Macular Degeneration.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {7915-7933},
pmid = {40551979},
issn = {1178-2013},
mesh = {Animals ; *Choroidal Neovascularization/drug therapy ; *Ginsenosides/administration &amp; dosage/chemistry/pharmacology ; *Oxidative Stress/drug effects ; *Oligopeptides/chemistry ; *Macular Degeneration/drug therapy/metabolism ; Mice ; Liposomes/chemistry ; Humans ; Cell Line ; Disease Models, Animal ; Angiogenesis Inhibitors/pharmacology/administration &amp; dosage/chemistry ; Vascular Endothelial Growth Factor A/metabolism ; Mice, Inbred C57BL ; Antioxidants/pharmacology/administration &amp; dosage/chemistry ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Reactive Oxygen Species/metabolism ; Intravitreal Injections ; Male ; },
abstract = {BACKGROUND AND AIM: Age-related macular degeneration (AMD) is a leading cause of vision loss owing to choroidal neovascularization (CNV) and retinal vascular abnormalities. Current anti-VEGF therapies often exhibit limited efficacy in approximately 50% of patients owing to the complex pathological microenvironment, including elevated reactive oxygen species (ROS) levels. This study aimed to develop a multitargeted therapeutic strategy for AMD by leveraging the antioxidant and anti-angiogenic properties of ginsenoside Rg3 (Rg3).<br><br>METHODS: RGD-Rg3@Lips was formulated to encapsulate Rg3 and modified with (Arginine-Glycine-Aspartic Acid, RGD) peptides for targeted delivery. In vitro studies have evaluated the cellular internalization, anti-angiogenic effects, and suppression of oxidative stress and inflammation in ARPE-19 cells. In vivo efficacy was assessed using a laser-induced AMD mouse model, in which an intravitreal injection of RGD-Rg3@Lips was administered. Mechanistic studies have focused on the hypoxia-inducible factor 1-&#x3b1;, (HIF-1&#x3b1;) / vascular endothelial growth factor, (VEGF) signaling pathway and the expression of inflammatory cytokines.<br><br>RESULTS: RGD-Rg3@Lips demonstrated superior cellular internalization and anti-angiogenic efficacy compared to Rg3@Lips and free Rg3 in vitro, significantly reducing oxidative stress and inflammation. In vivo, RGD-Rg3@Lips markedly reduced CNV formation and vascular leakage in an AMD mouse model. Mechanistically, RGD-Rg3@Lips attenuated oxidative stress, inhibited the HIF-1&#x3b1;/VEGF pathway, and downregulated key inflammatory cytokines including tumor necrosis factor &#x3b1; (TNF-&#x3b1;) and VEGF. RGD modification significantly improved the targeting of CNV lesions, enhancing therapeutic efficacy by specifically binding to vascular surface integrin receptors compared to non-modified liposomes and free Rg3.<br><br>CONCLUSION: This study highlights the potential of RGD-Rg3@Lips as a novel multitargeted therapeutic strategy for wet AMD. By combining the antioxidant and antiangiogenic properties of Rg3 with targeted drug delivery, RGD-Rg3@Lips offers a promising approach to address the limitations of current AMD therapies. These findings underscore the value of natural-product-based nanomedicine for the treatment of complex ocular diseases.},
}
@article {pmid40551957,
year = {2025},
author = {Aljuhani, HS and Hubayni, RA and Qedair, J and Bukhari, ZM and Alzahrani, A and Bawazir, RO and Badghaish, OS and Alqahtani, F},
title = {Efficacy and Safety of Aflibercept Biosimilars Relative to Reference Aflibercept Therapy for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1911-1918},
pmid = {40551957},
issn = {1177-5467},
abstract = {PURPOSE: To assess the efficacy and safety of aflibercept biosimilars compared to reference aflibercept therapy for neovascular age-related macular degeneration (nAMD) through a systematic review and meta-analysis.<br><br>METHODS: A comprehensive literature search was conducted across multiple databases. Randomized controlled trials comparing intravitreal aflibercept biosimilars with reference aflibercept in patients with nAMD were included. The outcomes were changes in best-corrected visual acuity (BCVA), retinal thickness, choroidal neovascularization (CNV) leakage area from baseline based on fluorescein angiography, and adverse events.<br><br>RESULTS: Five studies involving 2,039 patients were included. No statistically significant differences were found between aflibercept biosimilars and reference aflibercept in terms of BCVA (weighted mean difference [WMD]: 1.05; 95% CI: -0.62 to 2.71; p = 0.22), central subfield thickness (WMD: 3.33; 95% CI: -14.48 to 21.14; p = 0.71), or CNV (WMD: -0.23; 95% CI: -0.58 to 0.12; p = 0.20). SThe incidence of treatment-emergent adverse events was similar between groups.<br><br>CONCLUSION: Aflibercept biosimilars demonstrated comparable efficacy and safety profiles to reference aflibercept in the treatment of nAMD. These findings suggest that biosimilars may serve as a cost-effective alternative without compromising patient outcomes.},
}
@article {pmid40550705,
year = {2025},
author = {Gualino, V and Sohier, C and Sibert, M and Erginay, A and Varenne, F and Butterworth, J and Couturier, A and Gabrielle, PH and Soler, V and Creuzot-Garcher, C},
title = {Real-world faricimab switch in France: artificial intelligence-based detection of changes in exudative signs in difficult-to-treat neovascular age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40550705},
issn = {2397-3269},
mesh = {Humans ; Male ; Female ; Intravitreal Injections ; France/epidemiology ; Retrospective Studies ; *Artificial Intelligence ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Exudates and Transudates ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; Subretinal Fluid/diagnostic imaging ; Fluorescein Angiography/methods ; Drug Substitution ; Follow-Up Studies ; Antibodies, Bispecific ; },
abstract = {PURPOSE: Some patients with neovascular age-related macular degeneration (nAMD) have persistent signs of exudation under treatment with intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. We examined the real-world anatomical responses among patients with suboptimal response and switched to faricimab using artificial intelligence (AI)-based retinal fluid quantification.<br><br>METHODS: A retrospective, multicentric, cohort study of patients in France with exudative signs and switched to faricimab without a new loading phase, maintaining the same prior injection interval. The RetInSight Fluid Monitor AI software quantified subretinal (SRF) and intraretinal (IRF) fluid on spectral domain optical coherence tomography. The primary outcome was change in SRF and IRF volumes in the central 1 and 6&#x2009;mm retinal areas after one and two injections of faricimab.<br><br>RESULTS: 74 patients (74 eyes) were included (mean age: 81.5&#xb1;8.4 years, 49% male). Significant reductions were observed in mean 1&#x2009;mm IRF (-2.9&#xb1;18.3&#x2009;nl; p=0.002), mean 6&#x2009;mm IRF (-17.7&#xb1;71.1&#x2009;nl; p<0.001) and mean 6&#x2009;mm SRF (-24.8&#xb1;156.3&#x2009;nl; p<0.001) volumes after one injection. The proportion of dry eyes (<5&#x2009;nl for SRF and IRF in the 1 and 6&#x2009;mm areas) increased from 0% at baseline to 32.4% after one injection and 48.4% after two injections. Lower baseline SRF volumes were predictive of dry response after one injection (adjOR 0.965; p=0.028) and lower baseline IRF volumes were predictive of dry response after two injections (adjOR 0.373; p=0.051).<br><br>CONCLUSION: Nearly half of patients achieved a dry response after two injections. AI-assisted fluid quantification provided objective monitoring, identifying lower baseline SRF and IRF as predictive factors for good response. Limited patient inclusion means longer-term and larger prospective studies are now required using automated retinal fluid quantification to further refine the baseline characteristics of good switch responders to better adapt switch protocols.},
}
@article {pmid40550377,
year = {2025},
author = {Shui, M and Yang, G and Jiang, J and Wang, S and Liao, R},
title = {Mendelian randomization study of lipid metabolites reveals causal associations with age-related macular degeneration.},
journal = {Experimental gerontology},
volume = {208},
number = {},
pages = {112817},
doi = {10.1016/j.exger.2025.112817},
pmid = {40550377},
issn = {1873-6815},
mesh = {Humans ; *Macular Degeneration/genetics/metabolism/epidemiology ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; *Lipid Metabolism/genetics ; Aged ; Middle Aged ; Genome-Wide Association Study ; Male ; Female ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly, affecting approximately 8.7 % of individuals over 55 years old. Increasing evidence suggests that lipid metabolism plays a significant role in AMD pathogenesis, yet the causal relationships remain unclear. This study aims to elucidate the causal relationship between lipid metabolites and AMD using Mendelian randomization (MR) methodology.<br><br>METHODS: A two-sample MR analysis was conducted to explore the associations between specific lipid metabolites (such as bile acids, fatty acids, sphingolipids, and steroid hormones) and the incidence of AMD, as well as the potential causal effect of AMD on these lipid metabolites. Genetic variants significantly associated with these lipid metabolites were selected as instrumental variables (IVs). Data for AMD and lipid metabolites were sourced from the IEU GWAS database, covering over 209,000 cases and >16 million single nucleotide polymorphisms (SNPs). The MR analysis employed inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods to estimate causal relationships and address potential pleiotropy and heterogeneity.<br><br>RESULTS: IVW analysis revealed significant associations between several lipid metabolites and AMD. Specifically, higher levels of laurate were found to increase the risk of AMD by 3.532 times (OR&#xa0;=&#xa0;3.532, 95%CI 1.498-8.328, P&#xa0;<&#xa0;0.010). In contrast, dehydroepiandrosterone sulfate (DHEA-S) (OR&#xa0;=&#xa0;0.551, 95%CI 0.311-0.977, P&#xa0;=&#xa0;0.042) and palmitoyl sphingomyelin (OR&#xa0;=&#xa0;0.213, 95%CI 0.053-0.863, P&#xa0;=&#xa0;0.030) were protective, with DHEA-S and palmitoyl sphingomyelin levels reducing the risk of AMD by 44.9&#xa0;% and 78.7&#xa0;%, respectively. Sensitivity analyses using MR-Egger and weighted median methods supported these findings, highlighting consistent trends across different analytical approaches.<br><br>CONCLUSION: By clarifying these causal relationships, this research aims to provide insights that could inform the development of therapeutic strategies targeting lipid metabolism, ultimately improving outcomes for individuals at risk of AMD.},
}
@article {pmid40549133,
year = {2025},
author = {Küçükerdönmez, C and Tedford, SE},
title = {Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {8},
pages = {1843-1853},
pmid = {40549133},
issn = {2193-8245},
abstract = {INTRODUCTION: This study aimed to evaluate the safety and efficacy of multiwavelength photobiomodulation (PBM) treatment (Tx) in earlier stages of nonexudative (dry) age-related macular degeneration (AMD).<br><br>METHODS: Participants were enrolled with a diagnosis of dry AMD. Participants were treated with a single or repeated series of multiwavelength PBM treatment (LumiThera Valeda[&#xae;] Light Delivery System; 590, 660, and 850&#xa0;nm) delivered three times per week over 3-5&#xa0;weeks every 4&#xa0;months with follow-up extending out to 16&#xa0;months. Outcomes analyzed included visual acuity (VA), contrast sensitivity (CS), and electroretinography (ERG).<br><br>RESULTS: A total of 41 eyes (27 participants) were evaluated after single (1 series of Tx, n&#x2009;=&#x2009;41 eyes) and repeat (2-4 series of Tx, n&#x2009;=&#x2009;26 eyes) PBM treatment with up to 16&#xa0;months of follow-up. Participants were mostly female (n&#x2009;=&#x2009;22, 81.5%) with a mean time since AMD diagnosis of 5.6&#xa0;years. Participants enrolled had earlier stage dry AMD with better vision (~&#x2009;20/32 Snellen) and a mean baseline VA of 76.5 letters. Single and repeated PBM Tx improved VA, CS, multi-luminance ERG, and fixed luminance ERG parameters. No significant visual decline was noted in any outcome measure or signs of phototoxicity.<br><br>CONCLUSIONS: PBM treatment of patients with earlier stage dry AMD showed improvements on multiple visual outcome measures and no adverse effects. Earlier stage AMD populations may not show robust magnitude effects as their starting vision does not show serious deficits, however; as a result of the degenerative and progressive nature of the disease, repeat treatment and continued monitoring of these outcomes are of interest. These beneficial effects were improved with repeated PBM treatment series.},
}
@article {pmid40549132,
year = {2025},
author = {Gunderson, I and Burale, A and Best, BJ and Tung, CI and Huber, J and Marsh, L},
title = {Clinical Trial Simulation in Geographic Atrophy: Patient, Caregiver, and Trial Site Staff Perspectives.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {8},
pages = {1855-1868},
pmid = {40549132},
issn = {2193-8245},
abstract = {INTRODUCTION: The perspectives of patients with geographic atrophy (GA) should be considered when planning new clinical trials to ensure that real-world patient needs are addressed. The purpose of this study was to explore the perspectives of patients, caregivers, and trial site staff on designing and planning a phase 2 clinical trial in GA.<br><br>METHODS: This cross-sectional study included patients with GA and their caregivers, trial site staff, and investigators from Germany, the UK, and the USA. Participants were asked to spend 30&#xa0;min reviewing a simulated trial design communicated as a simple video animation with a voiceover. Subsequently, a 90-min web-assisted telephone interview and survey was conducted to identify problems with the design of the simulated trial and explore potential solutions and improvements.<br><br>RESULTS: Patients (n&#x2009;=&#x2009;11), caregivers (n&#x2009;=&#x2009;11), and site staff (n&#x2009;=&#x2009;16) completed the survey after reviewing the simulated trial design. Survey responses suggested that study recruitment could be facilitated via widespread advertisement and by including a short washout period, i.e., the time period during which patients receive no medication prior to commencing the study drug to ensure that other treatments do not impact the study results. Survey suggestions for reducing the burden of trial participation included minimizing the number and frequency of trial visits, enabling assessments to be completed at home, and making the schedule of trial visits flexible. Appropriate investment in study center facilities was recommended. In addition, survey respondents proposed that providing transport could be highly beneficial, potentially enabling patients and caregivers to attend trial visits more easily.<br><br>CONCLUSIONS: This study provides valuable information on the viewpoints of patients, caregivers, and trial site staff regarding trial design. Accounting for these perspectives when designing future clinical trials may help ensure successful trial completion and promote positive perceptions of clinical research.},
}
@article {pmid40548636,
year = {2025},
author = {Hang, A and Shao, A and Shea, M and Roux, MJ and Imai-Leonard, DM and Adams, DJ and Amano, T and Amarie, OV and Berberovic, Z and Bour, R and Bower, L and Leonard, BC and Brown, SD and Cho, SY and Clementson-Mobbs, S and D'Souza, AJ and Dickinson, M and Eskandarian, M and Flenniken, AM and Fuchs, H and Gailus-Durner, V and Heaney, J and Hérault, Y and Hrabe de Angelis, M and Hsu, CW and Jin, S and Joynson, R and Kang, YK and Kim, H and Masuya, H and Nam, KH and Noh, H and Nutter, LMJ and Palkova, M and Prochazka, J and Raishbrook, MJ and Riet, F and Salazar, J and Seavitt, JR and Sedlacek, R and Selloum, M and Seo, KY and Seong, JK and Shin, HS and Shiroishi, T and Sorg, T and Stewart, M and Tamura, M and Tolentino, H and Udensi, U and Wells, S and Wurst, W and Yoshiki, A and Meziane, H and Yiu, G and Sieving, PA and Lanoue, L and Lloyd, KCK and McKerlie, C and Moshiri, A and , },
title = {Ocular Phenotyping of Knockout Mice Identifies Genes Associated With Late Adult Retinal Phenotypes.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {64},
pmid = {40548636},
issn = {1552-5783},
support = {K08 EY027463/EY/NEI NIH HHS/United States ; R03 OD032622/OD/NIH HHS/United States ; U42 OD011175/OD/NIH HHS/United States ; U54 HG006364/HG/NHGRI NIH HHS/United States ; },
mesh = {Animals ; Mice, Knockout ; Mice ; Phenotype ; Disease Models, Animal ; Humans ; *Retina/pathology/metabolism ; *Macular Degeneration/genetics ; *Eye Proteins/genetics ; },
abstract = {PURPOSE: Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases.<br><br>METHODS: The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes (KEGG).<br><br>RESULTS: Screening of 587 late-adult mouse genes yielded 12 with abnormal retinal phenotypes, which corresponded to 20 human orthologs. Three of the 12 mouse genes and two of the 20 human orthologs were previously implicated in retinal pathology or physiology in a literature review. Although all of the genes demonstrated retinal pathology when deleted from the mouse genome, most do not have established roles in human retinal disease. Furthermore, human protein-protein analysis and biological pathway analysis yielded only a few relationships between the candidate gene list and that of known IRD and AMD genes, suggesting they may represent novel retinal functions.<br><br>CONCLUSIONS: We identified 12 mouse genes with significant late-adult abnormal retinal pathology, eight of which have not been previously implicated in either mouse or human retinal physiology or pathology. These serve as novel retinal disease gene candidates for late-onset retinal disease.},
}
@article {pmid40548629,
year = {2025},
author = {Tran, E and Rakesh, M and Li, G and Freeman, EE and Roy-Gagnon, MH},
title = {Does the Association Between Eye Disease and Cognitive Function Vary by Genetic Risk of Cognitive Decline? An Analysis of Hospital Data With Replication in the Canadian Longitudinal Study on Aging.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {71},
pmid = {40548629},
issn = {1552-5783},
mesh = {Humans ; Male ; Female ; *Polymorphism, Single Nucleotide ; Cross-Sectional Studies ; Aged ; *Aging/physiology ; Aged, 80 and over ; *Cognition/physiology ; Canada/epidemiology ; Longitudinal Studies ; *Genetic Predisposition to Disease ; Middle Aged ; *Intracellular Signaling Peptides and Proteins/genetics ; *Phosphoproteins/genetics ; Risk Factors ; *Macular Degeneration/genetics ; Genotype ; *Cognition Disorders/genetics/epidemiology ; *Glaucoma/genetics ; },
abstract = {PURPOSE: Age-related eye diseases are inconsistently associated with cognitive decline which could be due to effect modification. The purpose of this study was to investigate whether two genetic factors previously found to be associated with cognitive decline, the KIBRA (WWC1) and PDE7A/MTFR1 genes, modify the association between eye disease and cognitive function.<br><br>METHODS: Data from a Montreal hospital-based cross-sectional study (n = 302) were used for the primary analysis. Candidate single-nucleotide polymorphisms (SNPs) rs17070145 (KIBRA gene) and rs10808746 (PDE7A/MTFR1 gene) were included in linear regression models to test for effect modification of the relationship between eye disease (glaucoma or age-related macular degeneration [AMD]) and cognitive function. Six oral cognitive tests were used. A replication analysis was done using the Quebec data from the Canadian Longitudinal Study on Aging (CLSA) (n = 4238). Effect modifications by expanded genomic regions around the candidate SNPs were tested.<br><br>RESULTS: Three statistically significant interactions with two cognitive function measures -category verbal fluency and immediate story recall-were found in the Montreal study: glaucoma and AMD with rs17070145 and verbal fluency (P < 0.03) and glaucoma with rs10808746 with immediate story recall (P < 0.05). Similar interactions, although not with the same cognitive measure, were found in the CLSA: AMD with KIBRA and glaucoma with PDE7A/MTFR1.<br><br>CONCLUSIONS: Our results suggest that the KIBRA and PDE7A/MTFR1 genes may modify the association between eye disease and cognitive function. This knowledge may help to better understand the mechanism by which glaucoma and AMD are related to cognitive function.},
}
@article {pmid40548258,
year = {2025},
author = {Sun, Y and Wang, J and Zhang, Y and Shang, J and Liu, JX},
title = {ACOCMPMI: An Ant Colony Optimization Algorithm Based on Composite Multiscale Part Mutual Information for Detecting Epistatic Interactions.},
journal = {Human mutation},
volume = {2025},
number = {},
pages = {7656300},
pmid = {40548258},
issn = {1098-1004},
mesh = {*Epistasis, Genetic ; *Algorithms ; Humans ; Polymorphism, Single Nucleotide ; Bayes Theorem ; Models, Genetic ; Macular Degeneration/genetics ; *Computational Biology/methods ; Computer Simulation ; },
abstract = {Epistatic interaction detection plays a pivotal role in understanding the genetic mechanisms underlying complex diseases. The effectiveness of epistatic interaction detection methods primarily depends on their interaction quantification measures and search strategies. In this study, a two-stage ant colony optimization algorithm based on composite multiscale part mutual information (ACOCMPMI) is proposed for detecting epistatic interactions. In the first stage, composite multiscale part mutual information is developed to quantify epistatic interactions, and an improved ant colony optimization algorithm incorporating filter and memory strategies is employed to search for potential epistatic interactions. In the second stage, an exhaustive search strategy and a Bayesian network score are adopted to further identify epistatic interactions within the candidate SNP set obtained in the first stage. ACOCMPMI is compared with five state-of-the-art methods, including epiACO, FDHE-IW, AntEpiSeeker, SIPSO, and MACOED, using simulation data generated from 11 epistatic interaction models. Furthermore, ACOCMPMI is applied to detect epistatic interactions in a real dataset of age-related macular degeneration. The experimental results show that ACOCMPMI is a promising method for epistatic interaction detection.},
}
@article {pmid40546332,
year = {2025},
author = {Arbab, A and Habibi, A and Rabbani, H and Tajmirriahi, M},
title = {From Image to Sequence: Exploring Vision Transformers for Optical Coherence Tomography Classification.},
journal = {Journal of medical signals and sensors},
volume = {15},
number = {},
pages = {18},
pmid = {40546332},
issn = {2228-7477},
abstract = {BACKGROUND: Optical coherence tomography (OCT) is a pivotal imaging technique for the early detection and management of critical retinal diseases, notably diabetic macular edema and age-related macular degeneration. These conditions are significant global health concerns, affecting millions and leading to vision loss if not diagnosed promptly. Current methods for OCT image classification encounter specific challenges, such as the inherent complexity of retinal structures and considerable variability across different OCT datasets.<br><br>METHODS: This paper introduces a novel hybrid model that integrates the strengths of convolutional neural networks (CNNs) and vision transformer (ViT) to overcome these obstacles. The synergy between CNNs, which excel at extracting detailed localized features, and ViT, adept at recognizing long-range patterns, enables a more effective and comprehensive analysis of OCT images.<br><br>RESULTS: While our model achieves an accuracy of 99.80% on the OCT2017 dataset, its standout feature is its parameter efficiency-requiring only 6.9 million parameters, significantly fewer than larger, more complex models such as Xception and OpticNet-71.<br><br>CONCLUSION: This efficiency underscores the model's suitability for clinical settings, where computational resources may be limited but high accuracy and rapid diagnosis are imperative.Code Availability: The code for this study is available at https://github.com/Amir1831/ViT4OCT.},
}
@article {pmid40545017,
year = {2025},
author = {Ramirez, M and Kitayama, K and Puran, A and Tseng, VL and Yu, F and Coleman, AL},
title = {The Associations Between Glaucoma and Circadian Rhythm Sleep Disorders in California Medicare Beneficiaries.},
journal = {American journal of ophthalmology},
volume = {278},
number = {},
pages = {250-256},
doi = {10.1016/j.ajo.2025.06.021},
pmid = {40545017},
issn = {1879-1891},
mesh = {Humans ; Female ; Male ; Aged ; Cross-Sectional Studies ; United States ; Aged, 80 and over ; *Glaucoma/epidemiology/complications/physiopathology ; California/epidemiology ; *Sleep Disorders, Circadian Rhythm/epidemiology ; *Medicare/statistics &amp; numerical data ; Intraocular Pressure/physiology ; Retrospective Studies ; },
abstract = {PURPOSE: To examine the associations between glaucoma, circadian rhythm sleep disorders (CRSD), and any sleep-wake disorders in California (CA) Medicare beneficiaries.<br><br>DESIGN: Cross-sectional study.<br><br>SUBJECTS: All 2019 CA Medicare beneficiaries who were &#x2265;65 years old, had both Parts A &amp; B coverage, and had &#x2265;1 Part B claim.<br><br>METHODS: The primary exposure was a diagnosis of glaucoma as defined by International Classification of Diseases, 10th revision codes. The primary outcome was CRSD, and the secondary outcome was any sleep-wake disorder, defined by International Classification of Diseases, 10th revision codes. The associations between glaucoma, CRSD, and any sleep-wake disorders were estimated using multivariable logistic regression models adjusting for age, sex, race and ethnicity, age-related macular degeneration, diabetic retinopathy, cataracts, pseudophakia, and systemic disease burden defined by Charlson Comorbidity Index score. The effect estimate was expressed as an adjusted odds ratio (aOR) with a 95% confidence interval (CI).<br><br>MAIN OUTCOME MEASURES: Odds ratios between exposures and outcomes.<br><br>RESULTS: The study population included 2,717,346 CA Medicare beneficiaries meeting inclusion criteria. Of those, 220,662 (8.1%) had glaucoma, 3,202 (0.12%) had CRSD, and 355,390 (13.1%) had any sleep-wake disorder. In the adjusted logistic regression models, beneficiaries with glaucoma had greater adjusted odds of CRSD (aOR: 1.20; 95% CI: 1.06-1.35; P = .0031) and of any sleep-wake disorder (aOR: 1.12; 95% CI: 1.11-1.13; P < .001) compared to beneficiaries without glaucoma.<br><br>CONCLUSIONS: In the 2019 CA Medicare population, beneficiaries with glaucoma had increased likelihood of CRSD and of any sleep-wake disorder. Further investigations are needed to characterize mechanisms of these associations and to examine the impact of glaucoma treatment on sleep-wake disorders.},
}
@article {pmid40544279,
year = {2025},
author = {Huang, X and Li, T and Zhang, G and Chen, J and Li, T and Yang, S and Bo, Q and Zhao, X and Wan, X and Zhu, X and Yu, B and Sun, X and Sun, J},
title = {AIM2 activation mediated by RIPK1/3-dependent mitochondrial DNA release drives Aβ1-40-Induced retinal pigment epithelium injury.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {301},
pmid = {40544279},
issn = {1478-811X},
support = {82101159//National Natural Science Foundation of China/ ; 82101168//National Natural Science Foundation of China/ ; 82000882//National Natural Science Foundation of China/ ; 82301220//National Natural Science Foundation of China/ ; 82201223//National Natural Science Foundation of China/ ; 82471091//National Natural Science Foundation of China/ ; U22A20311, 82388101 and 82171076//National Natural Science Foundation of China/ ; 23YF1434100//"YangFan Program" of Shanghai Municipal Committee of Science and Technology/ ; 22PJ1412200//Shanghai Pujiang Program/ ; 2022YFC2502800//National Key R&amp;D Program/ ; 2023ZKZD18//Shanghai Municipal Education Commission/ ; 2023YFC2506100//National Key R&amp;D Program of China/ ; },
mesh = {Animals ; *Retinal Pigment Epithelium/pathology/metabolism/injuries ; *Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; *Amyloid beta-Peptides/toxicity/metabolism ; Mice ; *DNA, Mitochondrial/metabolism ; *DNA-Binding Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; Inflammasomes/metabolism ; Male ; *Peptide Fragments ; Signal Transduction ; },
abstract = {BACKGROUND: The retinal pigment epithelium (RPE) degeneration and subsequent retinal atrophy are hallmarks of age-related macular degeneration (AMD). Amyloid-beta (Aβ), the primary component of amyloid plaques in Alzheimer's disease (AD), is also present within drusen and is considered a critical factor contributing to RPE degeneration in AMD. Recent findings indicate that Aβ-induced inflammation plays a role in RPE degeneration. The aim of this study was to explore the molecular players and the precise mechanisms involved in this process, particularly the potential role of the absent in melanoma 2 (AIM2)-like receptors (ALRs) inflammasome.<br><br>METHODS: An animal model of A&#x3b2;1-40-induced RPE injury was established. Fundus photography, electrophysiology and hematoxylin-eosin staining were used to evaluate the morphological and functional RPE damage. Transcriptome sequencing was used to detect the differentially expressed genes between A&#x3b2;1-40 group and control group. The transcriptional and protein expression levels of AIM2 pathway and RIPK family members were detected. Adeno-associated virus vector 2/2 (AAV2/2)-shAIM2 was constructed to knockdown AIM2 expression in mice RPE cells. A&#x3b2;1-40-treated ARPE-19 cells and hRPE cells were employed to analyze the regulatory effects of RIPK family on mitochondrial DNA (mtDNA) release and AIM2 pathway activation.<br><br>RESULTS: A&#x3b2; induces RPE damage through stimulation of AIM2 inflammasome and augmentation of caspase-1 and interleukin-1&#x3b2; (IL-1&#x3b2;). Knocking down AIM2 inhibits the release of inflammatory cytokines and alleviates the degeneration of the retina and RPE. Simultaneously, A&#x3b2; triggers the activation of RIPK1/RIPK3 kinases, as manifested by heightened protein expression and phosphorylation. Inhibiting RIPK1/RIPK3 phosphorylation dampens AIM2 inflammasome activity and curtails IL-1&#x3b2; secretion. Mechanistically, RIPK1/RIPK3 inhibition attenuates A&#x3b2;-induced Drp1(S616) hyperphosphorylation, consequently reducing mitochondrial fission and the efflux of mitochondrial DNA (mtDNA) into the cytosol. The diminished mtDNA release is responsible for attenuated AIM2 activation and subsequent inactivation of the stimulator of interferon genes (STING)/nuclear factor-kappa-B (NF-&#x3ba;B) signaling cascade.<br><br>CONCLUSIONS: Our study is the first to validate AIM2's contribution in A&#x3b2;-induced RPE pathology and underscore the significance of the RIPK1/RIPK3-induced mtDNA release in modulating inflammatory responses, shedding light on the underlying mechanisms and potential therapeutics of AMD.},
}
@article {pmid40543797,
year = {2025},
author = {Finger, RP},
title = {Can interventional clinical trials be implemented in intermediate age-related macular degeneration?.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110493},
doi = {10.1016/j.exer.2025.110493},
pmid = {40543797},
issn = {1096-0007},
}
@article {pmid40543257,
year = {2025},
author = {Couturier, A and Souied, EH and Creuzot-Garcher, C and Cohen, SY and Kodjikian, L and Baillif, S and Delyfer, MN and Weber, M and Aubry-Quenet, I and Ponthieux, A and Devin, F},
title = {Disease control, visual and anatomic outcomes at week 48 of brolucizumab treatment in patients with previously suboptimal anatomically controlled neovascular age-related macular degeneration - The SWIFT study.},
journal = {Journal francais d'ophtalmologie},
volume = {48},
number = {7},
pages = {104574},
doi = {10.1016/j.jfo.2025.104574},
pmid = {40543257},
issn = {1773-0597},
mesh = {Humans ; Aged ; Female ; Male ; Visual Acuity/drug effects ; Middle Aged ; Treatment Outcome ; Intravitreal Injections ; Aged, 80 and over ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use/adverse effects ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use/adverse effects ; *Wet Macular Degeneration/drug therapy/pathology/epidemiology ; Prospective Studies ; France/epidemiology ; *Macular Degeneration/drug therapy/pathology ; Tomography, Optical Coherence ; *Choroidal Neovascularization/drug therapy/pathology ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) patients refractory to one anti-vascular endothelial growth factor (VEGF) agent often switch to another anti-VEGF for better disease control. Our objective is to assess nAMD control with brolucizumab 6mg treatment in previously treated patients with suboptimal anatomical control.<br><br>METHODS: SWIFT was a 48-week, prospective, single-arm, open-label clinical trial at 52&#xa0;sites in France (NCT04264819). Participants were adults (&#x2265;&#xa0;50&#xa0;years) with active CNV lesions secondary to nAMD, diagnosed<18&#xa0;months, previously treated with either ranibizumab or aflibercept with a 4- or 8-week interval treatment, with baseline BCVA 38-83&#xa0;letters. Eyes were treated with intravitreal brolucizumab 6mg at weeks 0, 4 and 8 (loading phase), followed by treat-to-control dosing with intervals up to 16&#xa0;weeks, depending on investigator-assessed disease activity. The main outcome is the proportion of eyes without investigator-assessed disease activity at week 16.<br><br>RESULTS: Two hundred and eighty-nine patients were included and analyzed (mean age 76.3&#xa0;years, 61.9% female). Eyes were previously treated for a mean of 9.1&#xa0;months. Baseline mean BCVA was 68.9&#xa0;letters, and central subfield foveal thickness (CSFT) was 417&#x3bc;m. Over the course of the study, patients received a median of 6&#xa0;brolucizumab injections (range: 1-8) with a mean (SD) treatment duration of 32.1 (14.1) weeks. The mean last brolucizumab treatment interval (SD) was 8.7 (3.5) weeks, notably longer than the interval of 6.2 (2.8) weeks with the previous anti-VEGF agent before inclusion in SWIFT. The proportion of eyes with no disease activity was 41.0% (95% CI: 34.4-47.9) at week 16 and 52.0% at week 48 (47.0 and 43.4%, respectively, using last observation carried forward sensitivity analysis). Improvements were observed from baseline to week 48 in BCVA (mean +3.2 [9.2] letters; P<0.0001), CFST (-66 [101] &#x3bc;m; P<0.0001). At week 48, 22% of eyes were on a regimen of every 12&#xa0;weeks or more, and 40.4% of eyes had no retinal fluid (36.0 and 42.4% had intraretinal and subretinal fluid respectively). Intraocular inflammation (IOI) was confirmed in 29/295 (9.8%) eyes. Four of these patients had BCVA losses of&#x2265;15&#xa0;letters at or after IOI resolution.<br><br>CONCLUSIONS: In patients with refractory nAMD, brolucizumab allowed control of disease activity for up to 41.0% of patients, with visuals gains, anatomical improvements and extended treatment interval, despite poor response and discontinuation for some patients in addition to a 9.8% rate of IOI.},
}
@article {pmid40542208,
year = {2025},
author = {Kojima, H and Shiragami, C and Yamashita, A and Miyoshi, Y and Osaka, R and Ono, A and Suzuma, K},
title = {Increased macular atrophy area with photodynamic therapy over intravitreal aflibercept at 2-year follow-up of pachychoroid neovasculopathy.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {4},
pages = {529-535},
pmid = {40542208},
issn = {1613-2246},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Recombinant Fusion Proteins/administration &amp; dosage ; Retrospective Studies ; *Photochemotherapy/methods/adverse effects ; Female ; Male ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; *Visual Acuity ; Fluorescein Angiography ; Aged ; Fundus Oculi ; *Macula Lutea/pathology ; *Choroid/pathology/blood supply ; *Choroidal Neovascularization/drug therapy/diagnosis ; Middle Aged ; Atrophy ; Time Factors ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Photosensitizing Agents/therapeutic use ; },
abstract = {PURPOSE: To compare the therapeutic outcomes of intravitreal aflibercept injection (IVA) and reduced-fluence photodynamic therapy (rfPDT) for pachychoroid neovasculopathy (PNV) over 2 years.<br><br>STUDY DESIGN: Observational, retrospective case series. Single-center study.<br><br>METHODS: This study involved 36 eyes of 36 patients with PNV. The IVA group comprised 18 eyes treated with IVA monotherapy (injection every 3 months followed by a pro re nata regimen), whereas the rfPDT group consisted of 18 eyes treated with rfPDT monotherapy. Post-treatment changes in best-corrected visual acuity (BCVA), macular atrophy (MA) area, central retinal thickness (CRT) and subfoveal choroidal thickness (SFCT) were compared between the 2 groups.<br><br>RESULTS: The IVA group received 8.94&#xa0;&#xb1;&#xa0;4.77 injections, whereas the rfPDT group received rfPDT 1.06 &#xb1; 0.24 times. The logMAR BCVA improved in both groups but did not differ between the 2 groups. The MA area increased from 0.163 &#xb1; 0.418&#xa0;mm[2] to 0.227 &#xb1; 0.480&#xa0;mm[2] (P = .024) and from 0.139 &#xb1; 0.402&#xa0;mm[2] to 0.597 &#xb1; 0.939&#xa0;mm[2] (P < .001) in the IVA and rfPDT groups, respectively, with the rfPDT group showing a greater increase than the IVA group (P = .013). The CRT was reduced in both groups but did not differ between the 2 groups. The SFCT was reduced in both groups, but the reduction was higher in the rfPDT group than in the IVA group (P = .027). The factors affecting change in the MA area were the treatment method and patient age.<br><br>CONCLUSIONS: The increase in the MA area and the decrease in the SFCT were greater in the rfPDT group than in the IVA group for PNV, suggesting that IVA may be preferred over rfPDT for PNV treatment.},
}
@article {pmid40542004,
year = {2025},
author = {Liermann, YN and Behning, C and Isselmann, B and Schmid, M and Dunbar, HMP and Luhmann, UFO and Finger, RP and Schmitz-Valckenberg, S and Holz, FG and Pfau, M and Luu, CD and Saßmannshausen, M and Thiele, S and , },
title = {Ellipsoid zone reflectivity as a functional imaging biomarker for age-related macular degeneration: a MACUSTAR study report.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {20093},
pmid = {40542004},
issn = {2045-2322},
mesh = {Humans ; Aged ; Female ; *Macular Degeneration/diagnostic imaging/physiopathology/pathology ; Male ; *Tomography, Optical Coherence/methods ; Biomarkers ; Visual Acuity/physiology ; Middle Aged ; *Retina/diagnostic imaging/physiopathology ; Aged, 80 and over ; Contrast Sensitivity ; Visual Field Tests ; },
abstract = {This study evaluated the functional relevance of relative ellipsoid zone reflectivity (rEZR) on spectral-domain optical coherence tomography as a structural biomarker for retinal integrity, focusing on its association with retinal function. Participants with age-related macular degeneration (AMD) and controls from the MACUSTAR study underwent functional testing, including mesopic fundus-controlled perimetry, best-corrected visual acuity, low-luminance visual acuity, low-luminance deficit, Moorfields Acuity Test, and Pelli-Robson contrast sensitivity, along with spectral-domain optical coherence tomography imaging. Structural and functional data were analyzed globally and spatially aligned for topographic analysis. Linear-mixed effects models, adjusted for age, sex, and eccentricity of the rEZR, assessed associations between rEZR and functional metrics. A total of 275 eyes (early AMD, n = 34; intermediate AMD, n = 152; late AMD, n = 36; controls, n = 53) from 275 participants (mean ± standard deviation age: 71.1 ± 7.2 years; 63.3% female) were included. In global analyses, rEZR was associated with the mean average threshold in mesopic fundus-controlled perimetry (coefficient estimate 0.0492, 95% confidence interval 0.0190-0.0794, p = 0.0015), low-luminance visual acuity (coefficient estimate - 0.0015, 95% confidence interval - 0.0026 to - 0.0004, p = 0.0092), Moorfields Acuity Test (coefficient estimate 0.0092, 95% confidence interval - 0.0022 to - 0.0001, p = 0.0285), and Pelli-Robson contrast sensitivity (coefficient estimate 0.0030, 95% confidence interval 0.0015-0.0045, p = 0.0001). Topographic analysis further revealed an association of rEZR with mesopic retinal sensitivity (coefficient estimate 0.0065, 95% confidence interval 0.0026-0.0104, p < 0.0001). Higher outer retinal reflectivity is linked to better retinal function in AMD and controls, supporting its potential as a biomarker for retinal integrity and function.},
}
@article {pmid40541565,
year = {2025},
author = {Cui, T and Ou, Q and Wang, Z and Zhou, Y and Xu, J and Liu, Y and Bi, Y and Jin, X and Chen, J and Gao, F and Wang, J and Zhang, J and Lu, L and Xu, GT and Jin, C and Tian, H and Xu, JY},
title = {Naphthalene Metabolites From Long-Term Environmental Tobacco Smoke Induce the Aging of Retinal Pigment Epithelium.},
journal = {Aging cell},
volume = {24},
number = {9},
pages = {e70150},
pmid = {40541565},
issn = {1474-9726},
support = {82373482//The National Natural Science Foundation of China/ ; 82271108//The National Natural Science Foundation of China/ ; 20234Y0113//Shanghai Municipal Health Commission/ ; 2023YFC2506100//The National Key Research and Development Program of China/ ; },
mesh = {Animals ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism ; *Naphthalenes/metabolism/toxicity ; Rats ; Male ; *Tobacco Smoke Pollution/adverse effects ; Cellular Senescence/drug effects ; Humans ; Rats, Sprague-Dawley ; DNA Damage ; *Smoke/adverse effects ; },
abstract = {Tobacco use is the main source of indoor air pollution and contains a variety of toxic components. The smoke from burning cigarettes is a key environmental risk factor that leads to accelerated aging and the occurrence of numerous diseases. Meanwhile, cigarette smoke and aging are both prominent risk factors for age-related macular degeneration (AMD). This study demonstrates that long-term exposure to cigarette smoke can impair retinal function and induce the aging of retinal pigment epithelium (RPE). Meanwhile, the plasma of rats after long-term exposure to cigarette smoke can trigger DNA damage and cellular senescence in vitro. In addition, naphthalene and its metabolites (1,2-dihydroxynaphthalene and 1,2-naphthoquinone) derived from cigarette smoke have been identified as an important factor contributing to RPE damage caused by cigarette exposure. Finally, we found that the aging of RPE induced by smoking can be alleviated through smoking cessation, probably because quitting smoking reduces the accumulation of these toxic chemicals in plasma and within the eyes.},
}
@article {pmid40540493,
year = {2025},
author = {Loke, JY and Rampal, S and Che Hamzah, J and Lim, YW and Kamalden, TA},
title = {Visual impairment in any eye adversely affects quality of life: Psychometric validation of the Malay NEI VFQ-25.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0324979},
pmid = {40540493},
issn = {1932-6203},
mesh = {Humans ; Male ; Female ; *Quality of Life ; *Psychometrics ; Middle Aged ; Malaysia ; Aged ; Cross-Sectional Studies ; Surveys and Questionnaires ; *Vision Disorders/psychology ; Reproducibility of Results ; Visual Acuity ; Adult ; },
abstract = {PURPOSE: To cross-culturally translate and adapt the National Eye Institute Visual Functioning Questionnaire (NEIVFQ-25) into Malay or Bahasa Malaysia, and to analyze its psychometric properties in a cohort of Malaysian patients with visual impairment from various causes.<br><br>DESIGN: Cross-sectional validation study.<br><br>METHODS: The NEI-VFQ 25 was translated and cross-culturally adapted into the Malay version. Total of 324 visually impaired patients caused by cataracts, glaucoma, age-related macular degeneration (ARMD) or diabetic macular edema (DME), and a control group were included. Psychometric analysis was performed including test-retest and internal consistency reliability, convergent validity, discriminant validity, and factor analysis. Clinical validity was measured by correlation of clinical measurements with subdomain scores and known-groups comparison.<br><br>RESULTS: Participants' average age was 60.4 years (SD 15.4) and 47.2% were male. The internal consistency was high in most subdomains, with Cronbach alpha ranging from 0.66-0.89. The test-retest reliability was high (intraclass correlation coefficient 0.92). Even when just one eye had impaired vision, participants scored much lower on the Malay NEIVFQ 25, highlighting how well the questionnaire reflects the real impact of visual impairment. Moderate correlations were detected between visual acuity and the 'General vision', 'Near Activities', 'Distance Activities', 'Social Functioning', 'Mental Health', 'Role Difficulties', 'Dependency' and 'Driving' subdomains suggesting that these subdomains were associated with central vision. Factor analysis demonstrated that 4 factors can be extracted from 12 subdomains.<br><br>CONCLUSIONS: This study revealed that the Malay version of the NEIVFQ-25 is a valid, reliable, and reproducible instrument to measure the vision-related quality of life in patients with visual impairment. Quality of life was adversely affected even with only one eye having poor vision.},
}
@article {pmid40540142,
year = {2025},
author = {Hoy, SM},
title = {Revakinagene Taroretcel: First Approval.},
journal = {Molecular diagnosis &amp; therapy},
volume = {29},
number = {4},
pages = {553-561},
pmid = {40540142},
issn = {1179-2000},
mesh = {Humans ; *Genetic Therapy/methods ; Retinal Pigment Epithelium/cytology/metabolism ; *Ciliary Neurotrophic Factor/genetics/therapeutic use ; Animals ; Drug Approval ; United States ; },
abstract = {Revakinagene taroretcel (revakinagene taroretcel-lwey; ENCELTO™) is an encapsulated cell-based gene therapy containing 200,000-440,000 allogeneic retinal pigment epithelial (RPE) cells expressing recombinant human ciliary neurotrophic factor (rhCNTF). Available as a single-dose intravitreal implant, it has been developed by Neurotech Pharmaceuticals, Inc. for the treatment of chronic retinal diseases. In March 2025, revakinagene taroretcel received its first approval for the treatment of adults with idiopathic macular telangiectasia (MacTel) type 2 in the USA. It is the first US FDA-approved treatment for this disease. Revakinagene taroretcel has been granted Orphan Drug Designation for retinitis pigmentosa and Fast Track Designation for retinitis pigmentosa and dry age-related macular degeneration in the USA. This article summarises the milestones in the development of revakinagene taroretcel leading to this first approval for the treatment of adults with idiopathic MacTel type 2 in the USA.},
}
@article {pmid40538770,
year = {2025},
author = {Pearlman, JA and Sheth, VS and Khanani, AM and Indjeian, VB and Brunstein, F and Kuruvilla, D and Maia, M and Dere, R and Ma, L and Chen, H and Datta, S and Willis, JR and Wiley, HE},
title = {Phase I Study of the Anti-interleukin 33 Fragment Antigen-Binding Region RO7303359 in Geographic Atrophy Secondary to Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100800},
pmid = {40538770},
issn = {2666-9145},
abstract = {PURPOSE: Interleukin (IL) 33 is a potent proinflammatory cytokine and a potential target in age-related macular degeneration (AMD) pathophysiology. This study evaluated RO7303359, an anti-IL-33 fragment antigen-binding region (Fab) targeting the IL-33/serum stimulation-2 (ST2) pathway, in patients with geographic atrophy (GA) secondary to AMD.<br><br>DESIGN: Phase I, open-label, multicenter, single-dose, dose-escalation study.<br><br>PARTICIPANTS: Patients with GA secondary to AMD.<br><br>METHODS: Patients received a single intravitreal (IVT) injection of RO7303359 (dose range, 1-20 mg).<br><br>MAIN OUTCOME MEASURES: The primary objective was to evaluate the safety and tolerability of RO7303359. The secondary objectives included assessing pharmacokinetics (PK), immune response, and pharmacodynamic (PD) biomarker activity. Pharmacodynamic biomarkers assessed in aqueous humor included CC motif chemokine ligand 2, CXC motif chemokine ligand 10, IL-6, and intercellular adhesion molecule 1.<br><br>RESULTS: Thirty-seven patients enrolled in the dose cohorts. Single IVT doses of RO7303359 demonstrated an acceptable safety profile up to 20 mg, with mild ocular adverse events reported. Pharmacokinetics analysis revealed dose-proportional exposure within expected ranges for an IVT-administered Fab. No treatment-emergent antidrug antibodies were observed. Evaluation of changes in aqueous humor PD biomarker levels failed to demonstrate a discernible effect on IL-33/ST2 pathway activity.<br><br>CONCLUSIONS: In this trial (ClinicalTrials.gov identifier, NCT04615325), while RO7303359 exhibited acceptable safety and PK profiles, absence of demonstrable effects on the IL-33/ST2 pathway using aqueous PD biomarkers resulted in discontinuation of development in GA. Further work is needed to evaluate the relevance of the IL-33/ST2 pathway in the pathophysiology of AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40537856,
year = {2025},
author = {Lynn, SA and Pandi, SPS and Sanchez-Bretano, A and Muir, AM and Parker, L and Chatelet, DS and Newall, T and Scott, JA and Keeling, E and Smyth, NR and Self, JE and Lotery, AJ and Lee, H and Ratnayaka, JA},
title = {A longitudinal study of the 5xFAD mouse retina delineates Amyloid beta (Aβ)-mediated retinal pathology from age-related changes.},
journal = {Alzheimer's research &amp; therapy},
volume = {17},
number = {1},
pages = {136},
pmid = {40537856},
issn = {1758-9193},
support = {NC3R Fellowship to S.A.L (NC/T002336/1)/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; Seed award and PhD studentship//Sight Research UK/ ; },
mesh = {Animals ; Mice, Transgenic ; *Retina/pathology/metabolism/physiopathology ; *Amyloid beta-Peptides/metabolism ; Male ; Female ; Longitudinal Studies ; *Aging/pathology ; Mice ; Disease Models, Animal ; Tomography, Optical Coherence ; *Macular Degeneration/pathology/genetics/metabolism ; Electroretinography ; Humans ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the commonest cause of irreversible blindness in developed societies. AMD coincides with advanced age to which genetic and lifestyle factors contribute additional risks. High levels of the Alzheimer's-linked Amyloid beta (Aβ) proteins are correlated with aged/AMD retinas. To delineate the role of Aβ in retinopathy from age-related changes, we used transgenic 5xFAD mice in a longitudinal study to recapitulate the aged/AMD Aβ-burden of the human retina.<br><br>METHODS: Mice were genotyped to exclude the retinal degeneration alleles Pde6b[rd1], Pde6brd8, Agouti, Tyr and Oca2. Retinas of 5xFAD and wildtype littermates (97 males/females in total) were longitudinally assessed until 15 months using non-invasive retinal scans: multi-focal electroretinography, optokinetic tracking, optical coherence tomography (OCT), colour fundus photography and fluorescein angiography. Mice were killed at 4, 8 and 15 months, and eyes enucleated for analyses by light, confocal and electron microscopy.<br><br>RESULTS: Age-related changes included a gradual decline of retinal activity in all mice. Subretinal/drusen-like deposits increased with age, but, like retinal vessel morphology and vessel integrity, showed no differences between cohorts. Diminished PSD95 levels indicated impaired photoreceptor-bipolar connectivity which correlated with age. Ultrastructural imaging showed increased electron-dense granules and undigested outer segments within retinal pigment epithelial cells with age. 5xFAD pathology included significant weight reduction vs. wildtype/littermates, which were pronounced in females. 8 month old 5xFAD mice had diminished A and B waves, though the age-related decline in wildtype mice abolished these subsequently. Visual acuity/function was also reduced in 14 month 5xFAD eyes. OCT revealed thickened photoreceptor nuclei and inner segments in 8 month 5xFAD retinae. Scrutiny of chorioretinal tissues revealed diminished photoreceptor nuclei in 4 month 5xFAD eyes, though differences were abolished as both cohorts aged. From 8 months onwards, 5xFAD mice possessed fewer bipolar cell nuclei.<br><br>CONCLUSIONS: Chronic A&#x3b2; exposure led to the earlier development of retinopathy-linked features, the identification of which advances our understanding of how A&#x3b2; contributes to multifaceted retinopathies. These were distinguishable from wider age-related changes and non-specific influences of retinal degeneration alleles in 5xFAD mice. Longitudinal analyses revealed sex and age-related limitations and important 3Rs considerations for future studies using 5xFAD mice.},
}
@article {pmid40537005,
year = {2026},
author = {Zhang, H and Mu, Y and Li, H and Li, X},
title = {Unfolded protein response in endoplasmic reticulum stress associated with retinal degenerative diseases: A promising therapeutic target.},
journal = {Neural regeneration research},
volume = {21},
number = {4},
pages = {1339-1352},
pmid = {40537005},
issn = {1673-5374},
support = {R01 DK126662/DK/NIDDK NIH HHS/United States ; R01 DK129241/DK/NIDDK NIH HHS/United States ; },
abstract = {The unfolded protein response is a cellular pathway activated to maintain proteostasis and prevent cell death when the endoplasmic reticulum is overwhelmed by unfolded proteins. However, if the unfolded protein response fails to restore endoplasmic reticulum homeostasis, it can trigger pro-inflammatory and pro-death signals, which are implicated in various malignancies and are currently being investigated for their role in retinal degenerative diseases. This paper reviews the role of the unfolded protein responsein addressing endoplasmic reticulumstress in retinal degenerative diseases. The accumulation of ubiquitylated misfolded proteins can lead to rapid destabilization of the proteome and cellular demise. Targeting endoplasmic reticulum stress to alleviate retinal pathologies involves multiple strategies, including the use of chemical chaperones such as 4-phenylbutyric acid and tauroursodeoxycholic acid, which enhance protein folding and reduce endoplasmic reticulum stress. Small molecule modulators that influence endoplasmic reticulum stress sensors, including those that increase the expression of the endoplasmic reticulum stress regulator X-box binding protein 1, are also potential therapeutic agents. Additionally, inhibitors of the RNAse activity of inositol-requiring transmembrane kinase/endoribonuclease 1, a key endoplasmic reticulum stress sensor, represent another class of drugs that could prevent the formation of toxic aggregates. The activation of nuclear receptors, such as PPAR and FXR, may also help mitigate ER stress. Furthermore, enhancing proteolysis through the induction of autophagy or the inhibition of deubiquitinating enzymes can assist in clearing misfolded proteins. Combination treatments that involve endoplasmic-reticulum-stress-targeting drugs and gene therapies are also being explored. Despite these potential therapeutic strategies, significant challenges remain in targeting endoplasmic reticulum stress for the treatment of retinal degeneration, and further research is essential to elucidate the mechanisms underlying human retinal diseases and to develop effective, well-tolerated drugs. The use of existing drugs that target inositol-requiring transmembrane kinase/endoribonuclease 1 and X-box binding protein 1 has been associated with adverse side effects, which have hindered their clinical translation. Moreover, signaling pathways downstream of endoplasmic reticulum stress sensors can contribute to therapy resistance. Addressing these limitations is crucial for developing drugs that can be effectively used in treating retinal dystrophies. In conclusion, while the unfolded protein response is a promising therapeutic target in retinal degenerative diseases, additional research and development efforts are imperative to overcome the current limitations and improve patient outcomes.},
}
@article {pmid40534793,
year = {2025},
author = {Yuan, YX and Wu, HY and Yuan, WJ and Zhong, YL and Xu, Z},
title = {Macular pigment optical density and measurement technology based on artificial intelligence: a narrative review.},
journal = {International journal of ophthalmology},
volume = {18},
number = {6},
pages = {1152-1162},
pmid = {40534793},
issn = {2222-3959},
abstract = {Macular pigment (MP) is a crucial pigment in the macular region. It plays an important role in filtering blue light, and exhibits anti-inflammatory and antioxidant properties. Macular pigment optical density (MPOD) is a key indicator for assessing the density of MP in the macular area and is closely associated with eye diseases, including age-related macular degeneration, diabetic retinopathy, and glaucoma. This review aims to explore the clinical significance of MPOD and its research value in ophthalmology and other medical fields. It summarizes the current MPOD measurement techniques, categorizing them into two main types (in vivo and in vitro), and discusses their respective advantages and limitations. Additionally, given the advancements in artificial intelligence (AI) and deep-learning technologies that offer new opportunities for improving MPOD assessment, this review analyzes the significant potential and future prospects of AI-based fundus image analysis in MPOD measurement. The goal of AI-based analysis is to provide faster and more accurate detection methods, thereby promoting further research and new clinical applications of MPOD in the field of ophthalmology.},
}
@article {pmid40533834,
year = {2025},
author = {Wang, TI and Qu, J and Tang, R and Shi, X and Ying, X and Tao, Y and Li, X},
title = {Prognostic factors in the treatment of polypoidal choroidal vasculopathy with conbercept: a post hoc analysis of the STAR study.},
journal = {Eye and vision (London, England)},
volume = {12},
number = {1},
pages = {24},
pmid = {40533834},
issn = {2326-0254},
support = {7232192//Natural Science Foundation of Beijing Municipality/ ; },
abstract = {BACKGROUND: A post hoc analysis of the STAR study, which was a 48-week, phase IV, multicenter randomized controlled multicenter clinical trial was performed. This study aims to identify the baseline factors associated with visual and anatomic changes over 48 weeks in the treatment of active polypoidal choroidal vasculopathy (PCV) with conbercept.<br><br>METHODS: In the STAR study, 249 participants were randomized to either the 3&#x2009;+&#x2009;Q12W (3 monthly injections followed by injections every 12&#xa0;weeks) or 3&#x2009;+&#x2009;TAE (3 monthly injections followed by treat and extend regimen) group. The association of 27 baseline factors with three outcomes-changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and maximum retinal thickness (MRT) from baseline to 48&#xa0;weeks-was investigated using univariate regression analysis followed by multivariate linear regression analysis.<br><br>RESULTS: The final multivariate model indicated that worse baseline BCVA (P&#x2009;<&#x2009;0.01), CRT&#x2009;&#x2264;&#x2009;400&#xa0;&#x3bc;m (P&#x2009;<&#x2009;0.01), fewer polypoidal lesions (P&#x2009;<&#x2009;0.01), and younger age at baseline (P&#x2009;=&#x2009;0.04) were associated with greater BCVA gain at week 48. Higher CRT and MRT at baseline were associated with a greater reduction in CRT and MRT at week 48, separately (P&#x2009;<&#x2009;0.01 and P&#x2009;<&#x2009;0.01, respectively). Smaller pigment epithelial detachment (PED) volume at baseline was associated with greater reductions in CRT and MRT at week 48 (both P&#x2009;<&#x2009;0.01). Eyes with relatively good BCVA (>&#x2009;73 letters) at baseline exhibited lower reductions in CRT and MRT at week 48 (P&#x2009;<&#x2009;0.01 and P&#x2009;=&#x2009;0.02, respectively). At week 48, eyes with hemorrhagic PEDs showed greater reductions in CRT and MRT than those with fibrovascular PEDs (P&#x2009;=&#x2009;0.02 and P&#x2009;=&#x2009;0.03, respectively). Furthermore, eyes with shallow irregular or sharp-peaked PEDs exhibited greater reductions in CRT (both P&#x2009;<&#x2009;0.01) and MRT (P&#x2009;=&#x2009;0.01 and P&#x2009;<&#x2009;0.01, respectively) than those with multilobular PEDs from baseline to week 48.<br><br>CONCLUSIONS: In Chinese patients with PCV receiving intravitreal injections of conbercept, baseline characteristics, including age, BCVA, CRT, MRT, number of polypoidal lesions, PED volume, and PED types and morphology, served as predictors of visual and anatomical changes over 48&#xa0;weeks.},
}
@article {pmid40532855,
year = {2025},
author = {Owsley, C and McGwin, G and Clark, ME and Gao, L and Gooden, L and Thomas, TN and Goerdt, L and Curcio, CA},
title = {Delayed Rod-Mediated Dark Adaptation Is Associated with Incidence and Early Progression of Age-Related Macular Degeneration: Alabama Study on Early Age-Related Macular Degeneration 2.},
journal = {Ophthalmology},
volume = {132},
number = {11},
pages = {1273-1283},
pmid = {40532855},
issn = {1549-4713},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Dark Adaptation/physiology ; Incidence ; Male ; Female ; Disease Progression ; Aged ; Visual Acuity/physiology ; Middle Aged ; *Retinal Rod Photoreceptor Cells/physiology ; Follow-Up Studies ; Alabama/epidemiology ; *Macular Degeneration/physiopathology/epidemiology/diagnosis ; Contrast Sensitivity/physiology ; Aged, 80 and over ; Longitudinal Studies ; },
abstract = {PURPOSE: To examine whether delayed rod-mediated dark adaptation (RMDA) in healthy older eyes and those with early age-related macular degeneration (AMD) is associated with AMD incidence and progression at follow-up, as compared with other visual functions reliant on rods, cones, or mixed rod-cone mediation.<br><br>DESIGN: Longitudinal study over 3 years.<br><br>PARTICIPANTS: Eyes from adults &#x2265;60 years of age with normal macular health or with early AMD at baseline.<br><br>METHODS: At baseline, eyes underwent fundus photography to establish AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step classification system. The following visual functions were tested in 1 eye at baseline (the study eye): RMDA, scotopic sensitivity, low-luminance acuity, mesopic contrast sensitivity, mesopic light sensitivity, visual acuity, and contrast sensitivity. Three years later at follow-up, fundus photography and the AREDS classification were repeated. Age-adjusted relative risks and 95% confidence intervals measured the association between visual functions and AMD incidence and progression for the study eye and the fellow eye at follow-up.<br><br>MAIN OUTCOME MEASURES: Presence and severity of AMD at the 3-year follow-up visit in the study and fellow eyes.<br><br>RESULTS: Healthy older eyes at baseline with delayed RMDA were 3.54 or 3.40 times more likely to have incident AMD at the 3-year follow-up in the study eye and the fellow eye, respectively, compared with eyes without delays. No other visual functions were associated with AMD incidence, except for low-luminance visual acuity in the study eye. Eyes with early AMD at baseline with delayed RMDA were 3.89 or 2.65 times more likely to have progressed at follow-up for the study and fellow eye, respectively. No other visual functions were associated with AMD progression at follow-up.<br><br>CONCLUSIONS: Rod-mediated dark adaptation is the only visual function of those tested that was associated with AMD incidence and progression over 3 years in healthy eyes or those with early AMD at baseline. Our results suggest that other visual functions are not useful for understanding AMD incidence and early progression risk. Interventions that eventually are designed to arrest early AMD progression or preventative measures in those at risk should consider RMDA a functional outcome measure.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40529115,
year = {2025},
author = {Agrawal, V and Gupta, A and Agrawal, V and Sheth, JU},
title = {Faricimab Outcomes in Chorioretinal Disorders: Indian Real-World Analysis (FOCUS Study).},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1855-1862},
pmid = {40529115},
issn = {1177-5467},
abstract = {PURPOSE: To assess the real-world efficacy and safety of intravitreal faricimab in treating Diabetic Macular Edema (DME), neovascular Age-related Macular Degeneration (nAMD), and Central Macular Edema (CME) secondary to retinal vein occlusion (RVO) in an Indian population.<br><br>PATIENTS AND METHODS: This single&#x2011;center, retrospective observational study reviewed the records of 49 patients (49 eyes) diagnosed with DME, nAMD, or cystoid macular edema secondary to RVO, who received a total of 150 intravitreal faricimab injections and were followed for at least 24&#x202f;weeks. Patients received intravitreal faricimab injections, with follow-up at four-week intervals. Outcome measures included changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT), along with resolution of intraretinal (IRF) and subretinal fluid (SRF) in nAMD patients.<br><br>RESULTS: Faricimab significantly improved BCVA and reduced CMT across all groups after a mean follow-up period of 33.31 (&#xb1; 7.41) weeks. DME patients' BCVA improved from 0.71 (&#xb1; 0.36) LogMAR to 0.46 (&#xb1; 0.35) LogMAR (P<0.0001), nAMD from 1.24 (&#xb1; 0.73) to 0.43 (&#xb1; 0.43) LogMAR (P=0.00003), and RVO from 0.78 (&#xb1; 0.32) to 0.38 (&#xb1; 24) LogMAR (P=0.02). CMT decreased from 454.43 (&#xb1; 164.76) &#xb5;m to 255.3 (&#xb1; 81.17) &#xb5;m (P<0.00001) overall. Significant reductions were also observed in IRF and SRF in nAMD patients, with IRF decreasing from 48% to 16% (P=0.008) and SRF from 100% to 20% (P<0.00001). No significant adverse events, including intraocular inflammation (IOI), were reported.<br><br>CONCLUSION: Faricimab demonstrated significant visual and anatomical improvements across all diagnostic groups, including off&#x2011;label use in RVO&#x2011;associated CME during the study period, showing promise as an effective treatment for DME, nAMD, and RVO. These real-world outcomes align with clinical trial data (TENAYA, LUCERNE, YOSEMITE, RHINE), underscoring faricimab's potential as an effective, dual-action therapy for chorioretinal disorders.},
}
@article {pmid40528396,
year = {2025},
author = {He, N and Wu, D and Luo, R and Cao, Z and Shan, S and Fei, Q and Wu, J and Bai, S},
title = {Development and optimisation of esculin-loaded chitosan microspheres for intravitreal injection.},
journal = {Journal of microencapsulation},
volume = {42},
number = {6},
pages = {593-612},
doi = {10.1080/02652048.2025.2515840},
pmid = {40528396},
issn = {1464-5246},
mesh = {*Chitosan/chemistry/pharmacokinetics ; *Microspheres ; Intravitreal Injections ; *Esculin/pharmacokinetics/administration &amp; dosage/chemistry ; Animals ; Particle Size ; Macular Degeneration/drug therapy ; Drug Liberation ; Drug Delivery Systems ; *Drug Carriers/chemistry ; Vitreous Body/metabolism ; },
abstract = {This study was to prepare the esculin-loaded chitosan microspheres for intravitreal injection and explore the feasibility of the treatment of macular degeneration. The microspheres were fabricated using an emulsification crosslinking technique. The drug loading, encapsulation efficiency, and mean particle diameter of the optimised esculin-loaded chitosan microspheres were 8.03 ± 1.30%, 93.03 ± 2.16%, and 4.81 ± 1.60 μm, respectively. The thermal stability evaluation at 25 °C demonstrated consistent particle diameter maintenance, with microspheres retaining sizes of 4.73 ± 1.75 μm and 4.89 ± 1.55 μm after 15 and 30 days' storage periods, respectively. The in vitro release profile demonstrated 80% cumulative drug release from the microspheres over a 72 h period. Subsequent pharmacokinetic analysis revealed significantly enhanced parameters in the vitreous humour following intravitreal administration, with the half-life (t1/2) reaching 879.88 ± 44.00 min and the area under curve (AUC) attaining 150.18 ± 2.28 × 10[3] mg·min/mL. Intravitreal injection of esculin-loaded chitosan microspheres offers a promising drug delivery system for the treatment of macular degeneration.},
}
@article {pmid40528210,
year = {2025},
author = {Heinke, A and Warter, A and Nagel, ID and Agnihotri, A and Mehta, NN and Galang, CMB and Deussen, DN and Bartsch, DG and Cheng, L and Ferreyra, HA and Freeman, WR},
title = {Faricimab for treatment-resistant choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD): seven-months results using artificial intelligence and OCTA.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {68},
pmid = {40528210},
issn = {2056-9920},
support = {OT2OD032644/GF/NIH HHS/United States ; R01EY016323/GF/NIH HHS/United States ; R01EY033847/GF/NIH HHS/United States ; },
abstract = {BACKGROUND: To analyze the therapeutic response to faricimab 6 mg/0.05 ml in eyes with neovascular AMD (nAMD) with refractory intra- and/or subretinal fluid due to choroidal neovascularization (CNV), previously unresponsive to 4 mg monthly aflibercept and combination therapy with anti-VEGF and long-acting steroids.<br><br>METHODS: A retrospective case series study of 22 eyes with unresponsive CNV, despite monthly intravitreal treatment (mean number of pre-faricimab injections: 35.52&#x2009;&#xb1;&#x2009;17.12). We evaluated therapeutic response in eyes with persistent intra/subretinal fluid (IRF/SRF) unresponsive to anti-VEGF double-dose (DD) monotherapy (4-mg aflibercept) and/or simultaneous DD anti-VEGF (4-mg aflibercept) with steroids (triamcinolone). Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and optical coherence tomography (OCT) measurements of central retinal thickness (CRT) were recorded for 7 follow-ups. Baseline and follow-up OCTs were examined by an AI-developed platform (Discovery OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland) to measure the volume of IRF, SRF, and pigment epithelium detachment (PED) in nanoliters (nL) and CRT in micrometers (&#x3bc;m). Paired t-test compared these parameters at baseline and after treatment. OCTA analysis of CNV before and after treatment with faricimab was conducted using Angio-Tool software.<br><br>RESULTS: Anatomic outcomes included mean CRT reduction of -25.3&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0118) at month-1, -16.15&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0414) at month-4, and -26.36&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.0129) after the 7th follow-up. AI-assisted software analysis showed a significant reduction of IRF, SRF, and PED volume at multiple time points after initiating faricimab. There was a non-significant improvement in BCVA.<br><br>CONCLUSIONS: Switching to faricimab improved anatomy in highly treatment-resistant CNV eyes, indicating its potential when other therapeutic options have failed.},
}
@article {pmid40526904,
year = {2025},
author = {Rouvas, A and Datseris, I and Malvina-Efthymia, T and Kardara, M and Theodossiadis, P and Gouliopoulos, N},
title = {LONG-TERM NATURAL COURSE OF AVASCULAR SEROUS PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {10},
pages = {1854-1861},
doi = {10.1097/IAE.0000000000004558},
pmid = {40526904},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Retinal Detachment/diagnosis/etiology ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Aged ; *Visual Acuity ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; Aged, 80 and over ; Disease Progression ; *Choroidal Neovascularization/diagnosis/etiology ; Fundus Oculi ; Middle Aged ; Risk Factors ; *Macular Degeneration/complications/diagnosis ; Time Factors ; *Wet Macular Degeneration/complications/diagnosis ; Indocyanine Green/administration &amp; dosage ; },
abstract = {PURPOSE: To investigate the long-term natural history of avascular serous pigment epithelial detachment (PED) in age-related macular degeneration and identify risk factors for choroidal neovascularization (CNV) development.<br><br>METHODS: This retrospective study analyzed 71 eyes from 50 patients with pure avascular serous PED because of age-related macular degeneration, diagnosed via fluorescein angiography and indocyanine-green angiography. Patients were followed for at least 12 months (mean follow-up: 54.9 months). Baseline and follow-up assessments included best-corrected visual acuity and optical coherence tomography measurements of PED height and diameter. Disease progression was categorized as stable, atrophic, or CNV development, and statistical analyses identified CNV risk factors.<br><br>RESULTS: Among studied eyes, 15.5% developed CNV, 21.1% progressed to atrophy, and 63.4% remained stable. Larger baseline PED height and diameter significantly correlated with CNV risk (P = 0.004 and P = 0.003, respectively). Every 100 &#xb5; m increase in PED height and diameter raised CNV risk by 50% and 10%, respectively. Best-corrected visual acuity declined in all groups, with greater deterioration in CNV and atrophic cases.<br><br>CONCLUSION: Larger PED height and diameter are significant CNV risk factors in avascular serous PED. OCT-based monitoring is crucial for early detection of high-risk cases, optimizing clinical management, and preventing vision loss in age-related macular degeneration patients.},
}
@article {pmid40526023,
year = {2025},
author = {Lee, H and Sharma, A and Woo, SJ},
title = {Clinical Trials of Aflibercept Biosimilars: A Review.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {41},
number = {7},
pages = {363-369},
doi = {10.1089/jop.2025.0040},
pmid = {40526023},
issn = {1557-7732},
mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage/pharmacology ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage/pharmacology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Diseases/drug therapy ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/pharmacology ; Clinical Trials, Phase III as Topic ; },
abstract = {Anti-vascular endothelial growth factor (VEGF) biologics have revolutionized the management of VEGF-driven retinal diseases, significantly improving visual outcomes for patients. Following the patent expiration of ranibizumab, multiple anti-VEGF biosimilars have been developed, with the first approved for ophthalmic use entering the market in 2022. More recently, the expiration of aflibercept market exclusivity in 2024 has led to the rapid development of aflibercept biosimilars-some already approved and others pending regulatory decisions. By offering clinically equivalent and cost-effective alternatives to reference biologics, biosimilars can lessen financial burdens and improve treatment adherence. Understanding the study designs of biosimilars can mitigate negative perceptions of biosimilars and promote their active implementation. In this review, we provide a comprehensive comparison of the designs of phase III clinical trials of aflibercept biosimilars, including recently published results.},
}
@article {pmid40525920,
year = {2025},
author = {Ji, R and Ishikawa, K and Tan, W and Mori, K and Tsukamoto, R and Matsunaga, N and Kiyohara, K and Fukuda, Y and Wada, I and Isobe, T and Tanihara, T and Yoshida, Y and Mayanagi, K and Oyama, K and Terada, Y and Otsuki, K and Hamamura, K and Kikuchi, H and Nakao, S and Yoshida, S and Kannan, R and Ohdo, S and Sonoda, KH},
title = {Liposome Encapsulation Enhances Ripasudil Therapeutic Efficacy Against Proliferative Vitreoretinal Diseases: Implications in Advanced Ocular Treatment.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {56},
pmid = {40525920},
issn = {1552-5783},
support = {R01 EY030141/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Vitreoretinopathy, Proliferative/drug therapy/metabolism ; Liposomes ; Rabbits ; *Isoquinolines/pharmacokinetics/administration &amp; dosage ; Retinal Pigment Epithelium/drug effects/pathology ; *Sulfonamides/pharmacokinetics/administration &amp; dosage ; Disease Models, Animal ; Humans ; Epithelial-Mesenchymal Transition/drug effects ; Intravitreal Injections ; },
abstract = {PURPOSE: Proliferative vitreoretinal diseases, such as proliferative vitreoretinopathy (PVR) and neovascular age-related macular degeneration (nAMD), pose substantial challenges in their advanced stages owing to the development of retinal fibrous membranes. Current therapeutic modalities, including surgical interventions for PVR and antivascular endothelial growth factor therapy for nAMD, cannot effectively manage intraocular fibrosis associated with epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) cells. Through drug screening, we identified ripasudil, a Rho-kinase inhibitor, as a remarkable suppressor of RPE-EMT. However, the short vitreal half-lives of small-molecule drugs, coupled with the limited stability of ripasudil in the ocular environment, impede its application in vitreoretinal diseases. Considering the advances in nanotechnology-assisted improvement in drug stability and cellular uptake as well as controlled release, we aimed to enhance the efficacy of ripasudil through liposome encapsulation.<br><br>METHODS: After ripasudil encapsulation, we performed comprehensive in vivo and in vitro analyses and pharmacokinetic studies.<br><br>RESULTS: Liposome-encapsulated ripasudil (Lipo-Ripa) demonstrated a substantial reduction in subretinal fibrosis in an advanced AMD model and more effective inhibition of PVR progression in rabbits than that induced by ripasudil alone. Pharmacokinetic studies revealed that Lipo-Ripa exhibited improved retention capacity in the vitreous and retina, alongside reduced permeability through the RPE barrier and increased cellular uptake. These characteristics resulted in a sustained elevation of drug concentration within the ocular tissues over time.<br><br>CONCLUSIONS: Our findings suggest that liposomal encapsulation of ripasudil supports enhanced bioavailability and effectiveness of the drug, presenting a promising innovative therapeutic approach for the treatment of proliferative vitreoretinopathy.},
}
@article {pmid40525639,
year = {2025},
author = {Yildiz, E and Bozuyuk, U and Yildiz, E and Wang, F and Han, M and Karacakol, AC and Sheehan, D and Yu, Y and Sitti, M},
title = {Magnetically Controllable and Degradable Milliscale Swimmers as Intraocular Drug Implants.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {34},
pages = {e07569},
pmid = {40525639},
issn = {2198-3844},
support = {834531//HORIZON EUROPE European Research Council/ ; 101059593//H2020 Marie Sk&#x142;odowska-Curie Actions/ ; },
mesh = {*Drug Implants ; Humans ; *Absorbable Implants ; Hydrogels/chemistry ; Polyethylene Glycols/chemistry ; Animals ; *Drug Delivery Systems/methods ; Printing, Three-Dimensional ; Indoles ; Polymers ; },
abstract = {Intraocular drug implants are increasingly used for retinal treatments, such as age-related macular degeneration and diabetic macular edema, due to the rapidly aging global population. Although these therapies show promise in arresting disease progression and improving vision, intraocular implant-based therapies can cause unexpected complications that require further surgery due to implant dislocation or uncontrolled drug release. These frequent complications of intraocular drug implants can be overcome using magnetically controllable degradable milliscale swimmers (MDMS) with a double-helix body morphology. A biodegradable hydrogel, polyethylene glycol diacrylate, is employed as the primary 3D printing material of MDMS, and it is magnetized by decorating it with biocompatible polydopamine-encapsulated iron-platinum nanoparticles. MDMS have comparable dimensions to commercial intraocular implants that achieve translational motions in both aqueous and vitreous bodies. They can be imaged in real-time using optical coherence tomography, ultrasound, and photoacoustic imaging. Thanks to their biodegradable hydrogel-based structure, they can be loaded with anti-inflammatory drug molecules and release the medications without disrupting retinal epithelial viability and barrier function, and decrease proinflammatory cytokine release significantly. These magnetically controllable swimmers, which degrade in a couple of months, can be used for less invasive and more precise intraocular drug delivery compared to commercial intraocular drug implants.},
}
@article {pmid40523530,
year = {2025},
author = {Tamaddon, M and Fazel, M and Rezaee, D and Khalilzad, MA and Majidpoor, J and Ahmadieh, H and Fattahi, MD and Namakin, K and Suri, F and Najafi, S},
title = {The role of microRNAs in the pathophysiology of the aging eye.},
journal = {Ageing research reviews},
volume = {111},
number = {},
pages = {102805},
doi = {10.1016/j.arr.2025.102805},
pmid = {40523530},
issn = {1872-9649},
mesh = {Humans ; *MicroRNAs/genetics/metabolism/physiology ; *Aging/genetics/pathology/physiology ; Animals ; *Eye Diseases/genetics/physiopathology/metabolism ; *Eye/physiopathology/metabolism ; },
abstract = {The human eye is a complex organ integral to visual perception, comprising multiple structures, including the retina, cornea, and lens. Vision loss affects over 2.2 billion individuals globally, with conditions, such as age-related macular degeneration, cataracts, glaucoma, and diabetic retinopathy, recognized as responsible for a majority of visual-impairing conditions. Recent research highlights the critical roles of microRNAs (miRNAs)-small non-coding RNAs involved in post-transcriptional gene regulation-in ocular physiology and pathophysiology. miRNAs regulate gene expression by binding to target mRNA, modulating multiple processes like cell growth, apoptosis, and differentiation. Dysregulation of miRNAs has been implicated in various age-related ocular disorders like retinopathy, glaucoma and age-related macular degeneration, thereby disrupting cellular homeostasis and promoting disease progression. Experimental evidence, primarily from murine models, reveals that miRNAs regulate photoreceptor differentiation, retinal development, and the survival of postmitotic retinal cells. Additionally, miRNA dysregulation offers potential diagnostic and therapeutic insights. This study explores the roles of miRNAs in ocular pathophysiology, emphasizing their involvement in the maintenance of retinal cell integrity and visual system homeostasis. Furthermore, the significance of miRNAs in the pathogenesis of various human ophthalmic diseases associated with advancing age is reviewed.},
}
@article {pmid40523306,
year = {2025},
author = {Sina, EM and Pena, J and Zafar, S and Bommakanti, NK and Kuriyan, AE and Yonekawa, Y},
title = {AUTOMATED MACHINE LEARNING CLASSIFICATION OF OPTICAL COHERENCE TOMOGRAPHY IMAGES OF RETINAL CONDITIONS USING GOOGLE CLOUD VERTEX ARTIFICIAL INTELLIGENCE.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {10},
pages = {1984-1990},
doi = {10.1097/IAE.0000000000004555},
pmid = {40523306},
issn = {1539-2864},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Machine Learning ; Male ; Female ; Aged ; Macular Edema ; *Diabetic Retinopathy ; *Retinal Vein Occlusion ; Artificial Intelligence ; Middle Aged ; *Retinal Diseases/diagnosis ; *Retina ; Aged, 80 and over ; Retrospective Studies ; *Epiretinal Membrane ; },
abstract = {PURPOSE: Automated machine learning is an artificial intelligence tool that streamlines image recognition model development. This study evaluates the diagnostic performance of Google Vertex AI automated machine learning in differentiating age-related macular degeneration (AMD), diabetic macular edema, epiretinal membrane, retinal vein occlusion, and healthy controls using optical coherence tomography images.<br><br>METHODS: A publicly available, validated optical coherence tomography data set of 1965 deidentified images from 759 patients was used. Images were labeled and uploaded to Vertex AI. A single-label classification model was trained, validated, and tested using an 80%-10%-10% split. Diagnostic metrics included area under the precision-recall curve (AUPRC), sensitivity, specificity, and positive and negative predictive value. A subanalysis evaluated neovascular versus nonneovascular AMD.<br><br>RESULTS: The automated machine learning model achieved high accuracy (AUPRC = 0.991), with sensitivity, specificity, and PPV of 95.9%, 96.9%, and 95.9%, respectively. AMD classification performed best (AUPRC = 0.999, precision = 98.4%, recall = 99.2%). Epiretinal membrane (AUPRC = 0.978, precision = 92.9%, recall = 86.7%) and diabetic macular edema (AUPRC = 0.895, precision = 81.3%, recall = 86.7%) followed. Retinal vein occlusion recall was 80% despite 100% precision. Neovascular AMD outperformed nonneovascular AMD (AUPRC = 0.963 vs. 0.915).<br><br>CONCLUSION: Our automated machine learning model accurately classifies optical coherence tomography images of retinal conditions, demonstrating performance comparable or superior to traditional ML methods. Its user-friendly design supports scalable AI-driven clinical integration.},
}
@article {pmid40523155,
year = {2025},
author = {Patel, P and Smith, BT},
title = {Extensive Network of Outer Retinal Tubulations.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {12},
pages = {e90-e91},
doi = {10.1097/IAE.0000000000004546},
pmid = {40523155},
issn = {1539-2864},
}
@article {pmid40522574,
year = {2025},
author = {Chen, X and Bian, H and Wu, Z},
title = {Validation of the Chinese version of the financial toxicity scale in patients with wet age-related macular degeneration.},
journal = {Journal of patient-reported outcomes},
volume = {9},
number = {1},
pages = {69},
pmid = {40522574},
issn = {2509-8020},
mesh = {Humans ; Female ; Male ; Aged ; *Wet Macular Degeneration/economics/drug therapy ; Reproducibility of Results ; China ; Surveys and Questionnaires/standards ; Aged, 80 and over ; Middle Aged ; },
abstract = {OBJECTIVE: to confirm the validity of the Comprehensive Score for Financial Toxicity (COST) Scale in Chinese patients with wet age-related macular degeneration.<br><br>METHODS: A tertiary hospital in Wuxi's ophthalmology outpatient clinic treated 217 patients with wet age-related macular degeneration (wAMD) were chosen using the convenience sample approach for a questionnaire survey between October 2023 and February 2024. The Chinese version of the COST and general patient information were included in the survey. Critical ratio analysis and correlation analysis were used to examine the items on the scale. The structural validity of the scale was evaluated using factor analysis, the reliability of the scale was evaluated using Cronbach's &#x3b1; coefficient and retest reliability, and the content validity of the scale was evaluated using the Content Validity Index (CVI).<br><br>RESULTS: The item analysis results demonstrated that high and low subgroups could be identified using The COST scale's Chinese translation (P&#x2009;<&#x2009;0.01).; A linear positive correlation was observed between the scores of each item and the scale's overall scores (r values of 0.243&#x2009;~&#x2009;0.878, P&#x2009;<&#x2009;0.01), and the scores of factor 1, factor 2, and factor 3 showed a linear positive correlation with the total scores of the scale (accordingly, r values were 0.974, 0.505, and 0.300; P&#x2009;<&#x2009;0.01). and the scores of each item were linearly and positively correlated with the scores of the common factors to which they belonged (r values of 0.642 to 1.000, P&#x2009;<&#x2009;0.01). Content validity showed that the I-CVI of each item was 0.857&#x2009;~&#x2009;1.00, and the S-CVI was 0.974. Three metrics in all, with a cumulative variance contribution rate of 67.739%, were obtained through exploratory factor analysis. Each item's loading on the corresponding dimensions varied from 0.638 to 0.954. The Cronbach's &#x3b1; coefficient for the entire scale was 0.876(95% CI: 0.85-0.899). The reliability of the retest was 0.970 (95% CI: 0.936-0.990).<br><br>CONCLUSION: The Chinese version of the COST scale shows potential applicability pending further validation.},
}
@article {pmid40521981,
year = {2025},
author = {Yang, R and Zong, T and Wang, N and Wang, F and Su, Y},
title = {NR4A1 Alleviates Subretinal Fibrosis by Inhibiting Macrophage to Myofibroblast Transition.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {47},
pmid = {40521981},
issn = {1552-5783},
mesh = {Animals ; *Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/physiology/biosynthesis/metabolism ; Mice ; *Macrophages/pathology/metabolism ; Fibrosis/metabolism ; *Myofibroblasts/pathology/metabolism ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Retinal Pigment Epithelium/pathology/metabolism ; Male ; Extracellular Matrix/metabolism ; Macular Degeneration/metabolism/pathology ; RNA, Small Interfering/genetics ; },
abstract = {PURPOSE: Subretinal fibrosis (SF) secondary to neovascular age-related macular degeneration (nAMD) is the most predominant cause of central visual impairment in all patients with AMD. NR4A1 is a member of the nuclear orphan receptor superfamily, and has shown inhibitory effects on fibrosis in tissues such as the dermis, intestines, and heart. Cytosporone B (Csn-B) is a natural agonist of NR4A1. This study aims to explore whether NR4A1 plays a role in SF associated with nAMD.<br><br>METHODS: Mice RPE-choroid-sclera flat mounts were prepared for serial observation of changes in macrophage infiltration, as well as macrophage to myofibroblast transformation (MMT). The morphology of MMT cells and differences in extracellular matrix (ECM) expression were further observed in TGF-&#x3b2;1-induced THP-1 cells. The role of NR4A1 in MMT was confirmed by small interfering RNA (siRNA) after changes in NR4A1 were observed. To determine whether NR4A1 could be a target for SF treatment, we intervened with the Csn-B and observed the MMT and SF changes.<br><br>RESULTS: Macrophages were rapidly recruited in the early stage and gradually decreased after the second week. MMT was observed in the lesions and the maximum number of MMT cells was observed at the third week. NR4A1 was transiently upregulated with induction, followed by a gradual decrease and a continuous phosphorylation. The knockdown of NR4A1 promoted MMT and ECM expression, whereas treatment with Csn-B had an inhibitory effect. P-NR4A1 expression was significantly suppressed in Csn-B-treated MMT cells. Finally, MK-2206 was found to inhibit sustained TGF-&#x3b2;1-induced NR4A1 phosphorylation and also ECM expression.<br><br>CONCLUSIONS: NR4A1 inhibits MMT and reduces ECM deposition in SF. Its agonist Csn-B inhibits MMT by inhibiting AKT-induced NR4A1 phosphorylation, which then attenuates SF.},
}
@article {pmid40521080,
year = {2025},
author = {Jia, Q and Zha, Z and Li, S and Zhang, Y and Ke, L and Liu, S},
title = {Genetic Correlation and Mendelian Randomization Analyses Support Causal Relationships Between Instant Coffee and Age-Related Macular Degeneration.},
journal = {Food science &amp; nutrition},
volume = {13},
number = {6},
pages = {e70439},
pmid = {40521080},
issn = {2048-7177},
abstract = {Coffee is a popular beverage, and previous cohort studies suggest it may reduce the risk of age-related macular degeneration (AMD). However, confounding factors in these studies necessitate further exploration of causal relationships using advanced methods. We obtained data on coffee consumption from genome-wide association studies (GWAS) and the latest AMD-related GWAS summary data from the Finngen consortium R11. We assessed their genetic correlation using linkage disequilibrium score regression (LDSC), explored causal associations using Mendelian randomization (MR), and identified shared genetic loci via colocalization. Our results revealed a genetic correlation between instant coffee consumption and dry AMD, with each standard deviation (SD) increase in instant coffee intake associated with a corresponding odds ratio (OR) of approximately 6.92 for dry AMD, indicating a 6.92-fold increased risk. However, colocalization analysis did not show shared genetic variants between instant coffee consumption and AMD. Instant coffee may increase the risk of AMD, and reducing its intake could help prevent dry AMD. People at high-risk for AMD should avoid instant coffee. This study aids clinicians in identifying dietary factors, particularly instant coffee consumption, as potential risks for AMD. By providing genetically based causal evidence, our findings support the development of personalized AMD prevention strategies. Clinicians can advise patients to reduce instant coffee intake based on genetic risk profiles, offering a precision approach to reduce dry AMD risk. These interventions may significantly contribute to AMD prevention and treatment.},
}
@article {pmid40520473,
year = {2025},
author = {Hunt, PW and Olshen, AB and Murad, N and Ambayec, GC and Sezgin, E and Schneider, MF and Jabs, DA},
title = {Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100794},
pmid = {40520473},
issn = {2666-9145},
abstract = {OBJECTIVE: To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach.<br><br>DESIGN: A nested case-control study (analysis 1) and nested cohort study (analysis 2).<br><br>PARTICIPANTS: Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA).<br><br>METHODS: Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality.<br><br>MAIN OUTCOME MEASURES: Incident intermediate-stage AMD; incident cataract; and mortality.<br><br>RESULTS: Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q < 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1&#x3b2; pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality.<br><br>CONCLUSIONS: Upregulation of the IL-1&#x3b2; pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1&#x3b2; pathway may provide a therapeutic avenue for treatment of AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40520173,
year = {2025},
author = {Yang, N and Xiong, C and Feng, S and Gao, M and Zhou, S and Hui, Q and Zhou, X and Jin, Q and Shao, Y and Xu, X},
title = {Modified ZhuJing pill protects retinal pigment epithelium against oxidative stress-induced epithelial-mesenchymal transition through Nrf2-mediated Akt/GSK3β pathway.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1545731},
pmid = {40520173},
issn = {1663-9812},
abstract = {BACKGROUND: The modified ZhuJing pill (mZJP) has been widely used in China as a classical prescription for treating retinal diseases for years. Our preliminary experiment showed that mZJP exerted an antioxidant effect in treating dry age-related macular degeneration (AMD). Nevertheless, the specific mechanism underpinning the impact of mZJP on dry AMD remains obscure.<br><br>METHODS: The chemical metabolites of mZJP were qualitatively analyzed using LC-Q-TOF-MS. Dry AMD model mice were used to assess the efficacy of mZJP through optical coherence tomography (OCT), fundus autofluorescence (FAF), and immunofluorescence. Epithelial-mesenchymal transition (EMT) in OxLDL-induced ARPE-19 cells was evaluated by monitoring cellular integrity and quantifying EMT-related markers. Cell migration capacity was determined via wound healing and transwell assays. To investigate molecular mechanisms, cells were transfected with Nrf2 siRNA and analyzed through Western blotting, immunofluorescence, and migration assays under Nrf2 inhibition.<br><br>RESULTS: A total of 113 major metabolites were identified in mZJP. Our findings revealed that mZJP alleviated retinal pathological alterations and inhibited EMT progression. Furthermore, mZJP upregulated Nrf2 and HO-1 expression levels while downregulating Akt and GSK-3&#x3b2; phosphorylation levels. Notably, the EMT-suppressing effect of mZJP was significantly attenuated upon Nrf2 silencing, as evidenced by enhanced cell migration, decreased epithelial marker expression (E-cadherin), increased mesenchymal marker expression (vimentin and &#x3b1;-SMA), suppression of the Nrf2 pathway, and activation of the Akt/GSK3&#x3b2; pathway.<br><br>CONCLUSION: Our study suggested that RPE protection by mZJP against oxidative stress induced EMT through Nrf2 activation and inhibition of the Akt/GSK3&#x3b2; pathway. MZJP could be a potential candidate drug for the treatment of dry AMD.},
}
@article {pmid40519319,
year = {2025},
author = {Yao, J and Liu, Y and Zheng, J and Li, H and Lv, X},
title = {Association between dyslipidemia and neovascular age-related macular degeneration: a case-control study.},
journal = {International journal of clinical and experimental pathology},
volume = {18},
number = {5},
pages = {191-198},
pmid = {40519319},
issn = {1936-2625},
abstract = {OBJECTIVES: Neovascular age-related macular degeneration (nAMD) is an advanced stage of AMD and is associated with an increased risk of visual impairment. Disturbances in lipid metabolism have been proposed as a major contributing factor to the pathogenesis of AMD. This study aims to investigate whether lipid profiles in the serum and components of dyslipidemia can be used as indicators for predicting progression to nAMD.<br><br>METHODS: A retrospective analysis was conducted involving 125 participants with nAMD. 125 non-AMD controls, matched by age, sex, and BMI, were incorporated into the study. The comparative analysis between the groups involved six lipid biomarkers in the serum: HDL-C, LDL-C TG, TC, ApoA1, and ApoB. Moreover, the existence of dyslipidemia and its constituents was assessed through t-tests, as well as univariate and multivariable logistic regression models.<br><br>RESULTS: Individuals with nAMD exhibited significantly higher serum HDL-C (P = 0.02) compared to the controls without AMD. Furthermore, the concentrations of ApoB were significantly less in the nAMD cohort (P < 0.01) when compared to the control group. During the investigation of the correlation between levels of serum HDL-C (P < 0.01) and serum ApoB (P < 0.01) with nAMD through logistic regression analysis, notable findings indicated a significant association between both variables and nAMD. However, by multivariate logistic regression analysis, neither serum HDL-C nor serum ApoB was an independent risk factor for nAMD.<br><br>CONCLUSIONS: While individuals with nAMD demonstrated elevated serum HDL-C and reduced serum ApoB levels, these lipid markers may not be suitable as biomarkers for monitoring or preventing nAMD.},
}
@article {pmid40518488,
year = {2025},
author = {Huang, C and Tian, H and Li, W},
title = {Age-independent anti-angiogenic therapy for choroidal neovascularization by targeting secretogranin III.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {40518488},
issn = {2509-2723},
support = {R44EY027665/EY/NEI NIH HHS/United States ; R01 EY027749/EY/NEI NIH HHS/United States ; R01 EY036417/EY/NEI NIH HHS/United States ; R24 EY028764/EY/NEI NIH HHS/United States ; R21EY035421/EY/NEI NIH HHS/United States ; R44 EY027665/EY/NEI NIH HHS/United States ; R43 EY032827/EY/NEI NIH HHS/United States ; R43EY032827/EY/NEI NIH HHS/United States ; R21 EY035421/EY/NEI NIH HHS/United States ; R01EY027749/EY/NEI NIH HHS/United States ; R24EY028764/EY/NEI NIH HHS/United States ; R01EY036417/EY/NEI NIH HHS/United States ; },
abstract = {Recent studies reported that anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) alleviate choroidal neovascularization (CNV) in young but not aged animals. We recently developed a disease-targeted anti-angiogenic therapy against secretogranin III (Scg3), which selectively binds to diseased but not healthy vessels in young mice. Herein, using a unique in vivo ligand binding assay, we predicted and confirmed that Scg3 selectively binds CNV vessels in both young and aged mice. In contrast, VEGF with minimal increased binding to CNV vessels exhibited an age-dependent decline in binding to both CNV and healthy vessels with negligible binding in aged mice. Based on these binding activity patterns, we further predicted and confirmed that a humanized anti-Scg3 antibody effectively alleviated laser-induced CNV in both young and aged mice, whereas the anti-VEGF drug aflibercept was effective only in young mice. These findings suggest that enhanced binding of Scg3 to CNV vessels in both age groups provides a molecular basis for an age-independent anti-Scg3 therapy, offering potential to address anti-VEGF resistance in clinical treatment of wet age-related macular degeneration with CNV.},
}
@article {pmid40517987,
year = {2025},
author = {He, HL and An, GQ and Qi, Y and Yu, XB and Zhao, MW and Song, ZM and Jin, XM and Du, LP and Jin, ZB},
title = {Clinical characteristics of atrophic macular hole in pathologic myopia: A multicenter study.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {54},
number = {},
pages = {104680},
doi = {10.1016/j.pdpdt.2025.104680},
pmid = {40517987},
issn = {1873-1597},
mesh = {Humans ; Female ; *Retinal Perforations/diagnostic imaging/etiology/pathology ; Male ; Retrospective Studies ; Middle Aged ; *Myopia, Degenerative/complications ; Aged ; Visual Acuity ; Tomography, Optical Coherence/methods ; Choroidal Neovascularization ; },
abstract = {PURPOSE: This study aims to describe and analyze the clinical characteristics of atrophic macular hole (AMH), a severe complication in patients with pathologic myopia (PM).<br><br>METHODS: A multicenter, retrospective analysis was conducted involving 17 patients (17 eyes) diagnosed with AMH and 52 patients (52 eyes) diagnosed with simple macular hole (SMH) in PM from January 2023 to December 2023. Clinical data and multimodal images were collected. The age, gender, spherical equivalent (SE), axial length (AL), and best-corrected visual acuity (BCVA) of patients with AMH were described and their imaging characteristics analyzed.<br><br>RESULTS: Of the 17 patients diagnosed with AMH, 15 (88.24 %) were female; the mean age was 64.59&#xb1;12.61 years; the SE was -17.85&#xb1;4.15 D; the AL was 30.40&#xb1;1.67 mm; and the BCVA was 1.30 (1.00, 1.35) logMAR. Eleven eyes (64.71 %) exhibited myopic foveoschisis, seven eyes showed choroidal neovascularization (Fuchs spot), one eye had a concomitant epiretinal membrane, and no cases of retinal detachment involving the macula were observed. Axial length and neovascularization were significant correlates of BCVA in AMH patients (P < 0.05). Compared with SMH in PM, patients with AMH were older (t = 2.247, P = 0.028) and had worse BCVA (Z = 375, P = 0.037); no significant differences were found between the two groups in terms of gender, SE, and AL (P > 0.05).<br><br>CONCLUSION: We propose the term "atrophic macular hole" to describe a condition resembling a macular hole accompanied by atrophy of the RPE and choroid, caused by progressive degeneration of the outer retina or traction of the eyeball, which severely impairs central vision in patients.},
}
@article {pmid40517351,
year = {2025},
author = {Mhmud, H and Vermeulen, JP and Tigchelaar-Besling, OAM and Verbraak, FD and Barthelmes, D and Gillies, M and Ponsioen, TL and Klaver, CCW},
title = {Real-World 5-Year Outcomes of Age-Related Macular Degeneration with Bevacizumab as First-Line Anti-VEGF.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {8},
pages = {1813-1826},
pmid = {40517351},
issn = {2193-8245},
abstract = {INTRODUCTION: To evaluate long-term outcomes of anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) in the Netherlands (NL), where bevacizumab is the mandated first-line drug, compared to high-income countries using ranibizumab or aflibercept as initial treatments.<br><br>METHODS: Five-year data from the Fight Retinal Blindness! (FRB) registry, a real-world prospective registry, were analyzed. Outcomes from 1473 Dutch eyes (1229 patients) treated with bevacizumab were compared with 7144 eyes (5884 patients) in a reference group (RG) from 13 socioeconomically similar countries. The primary outcome was mean visual acuity (VA) at yearly intervals; secondary outcomes included injection frequency and switching rates to alternative anti-VEGF agents.<br><br>RESULTS: Throughout the 60&#xa0;months, mean VA was consistently higher in Dutch eyes (baseline: NL 60.2 vs. RG 59.2; 60&#xa0;months: NL 64.9 vs. RG 62.6). The Dutch group cumulatively received 14.5 more injections over 5&#xa0;years and had a higher rate of switching (70.9% vs. 50.9%) with a shorter median time to switching (11.9&#xa0;months vs. 17.7&#xa0;months).<br><br>CONCLUSIONS: Patients treated in Dutch FRB! clinics have good long-term outcomes with a 2.3-letter higher mean VA at the 60-month timepoint compared to FRB! clinics in the RG. The Dutch patients, who began treatment with bevacizumab, received 14.5 more injections over 5&#xa0;years and had a 40% higher rate of switching to an alternative drug, with switching occurring 5.8&#xa0;months earlier. This study highlights the benefits of early and more intensive management to optimize visual outcomes, which appear more important than the choice and price of the first-line drug.},
}
@article {pmid40517179,
year = {2025},
author = {Ma, K and Nakajima, H and Basak, N and Barman, A and Ratnapriya, R},
title = {Integrating explainable machine learning and transcriptomics data reveals cell-type specific immune signatures underlying macular degeneration.},
journal = {NPJ genomic medicine},
volume = {10},
number = {1},
pages = {48},
pmid = {40517179},
issn = {2056-7944},
abstract = {Genome-wide association studies (GWAS) have established key role of immune dysfunction in Age-related Macular Degeneration (AMD), though the precise role of immune cells remains unclear. Here, we develop an explainable machine-learning pipeline (ML) using transcriptome data of 453 donor retinas, identifying 81 genes distinguishing AMD from controls (AUC-ROC of 0.80, CI 0.70-0.92). Most of these genes were enriched in their expression within retinal glial cells, particularly microglia and astrocytes. Their role in AMD was further strengthened by cellular deconvolution, which identified distinct differences in microglia and astrocytes between normal and AMD. We corroborated these findings using independent single-cell data, where several ML genes exhibited differential expression. Finally, the integration of AMD-GWAS data identified a regulatory variant, rs4133124 at PLCG2, as a novel AMD association. Collectively, our study provides molecular insights into the recurring theme of immune dysfunction in AMD and highlights the significance of glial cell differences in AMD progression.},
}
@article {pmid40515815,
year = {2025},
author = {Torrell-Belzach, N and Souied, EH and Le, HM and Benlahbib, M and Dobbels, Z and Gounfle, AE and Wang, XX and Jung, C and Miere, A},
title = {Comparison of choriocapillaris perfusion between swept-source optical coherence tomography angiography and spectral-domain optical coherence tomography angiography in five different choriocapillaris slabs in patients with intermediate age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {9},
pages = {2495-2504},
pmid = {40515815},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Choroid/blood supply ; Cross-Sectional Studies ; Female ; Male ; Aged ; Capillaries/physiopathology/diagnostic imaging ; Fundus Oculi ; *Retinal Vessels/physiopathology/diagnostic imaging ; Regional Blood Flow/physiology ; Aged, 80 and over ; Middle Aged ; Visual Acuity ; Retrospective Studies ; },
abstract = {PURPOSE: To analyze choriocapillaris (CC) perfusion using swept-source optical coherence tomography angiography (SS-OCTA) and spectral-domain optical coherence tomography angiography (SD-OCTA) in five CC slabs in patients with intermediate age-related macular degeneration (iAMD).<br><br>METHODS: This is a cross-sectional study of 23 eyes of 20 patients who underwent three 3&#x2009;&#xd7;&#x2009;3&#xa0;mm OCTA, one with SS-OCTA and two with SD-OCTA, a non-averaged scan (V1) and a four-scan volume (V4). Percentage of flow deficits (FD%), average size of FD (&#xb5;m2), total area of FD (mm2) and number of FD were calculated in different CC slabs (automatic, 11-21&#xa0;&#x3bc;m, 21-31&#xa0;&#x3bc;m, 31-41&#xa0;&#x3bc;m, 16-31&#xa0;&#x3bc;m).<br><br>RESULTS: There was a statistically significant difference in all parameters and all slabs analyzed, when comparing SS-OCTA versus SD-OCTA V1 and SD-OCTA V1 versus SD-OCTA V4. Nevertheless, when comparing SS-OCTA versus SD-OCTA V4, significant differences were only found for the automatic and the 31-41&#xa0;&#x3bc;m slab. When comparing the FD% between different slabs on the same device, significant differences were also found.<br><br>CONCLUSION: Quantification of CC FD% is impacted by the CC slab, the type of OCTA used, and volume averaging in SD-OCTA. Given the significant impact on quantitative results, comparisons between studies and instruments and/or with/without averaging are difficult, even at the same slab depth.},
}
@article {pmid40515626,
year = {2025},
author = {O'Neil, A and Welikala, RA and Barman, S and Owen, CG and Rudnicka, AR and Rakesh, M and Roy-Gagnon, MH and Maberley, D and Freeman, EE},
title = {Retinal Vessel Traits and Age-Related Eye Disease in the Canadian Longitudinal Study on Aging.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {7},
pages = {764-772},
pmid = {40515626},
issn = {1442-9071},
support = {//Canada Foundation for Innovation/ ; LSA 94473/CAPMC/CIHR/Canada ; PJT-183690/CAPMC/CIHR/Canada ; LSA 94473/CAPMC/CIHR/Canada ; PJT-183690/CAPMC/CIHR/Canada ; },
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Canada/epidemiology ; Aged ; Intraocular Pressure/physiology ; *Aging/physiology ; *Retinal Vessels/pathology ; Follow-Up Studies ; *Macular Degeneration/epidemiology/physiopathology/diagnosis ; Middle Aged ; Longitudinal Studies ; Aged, 80 and over ; *Glaucoma/physiopathology/epidemiology/diagnosis ; Tomography, Optical Coherence/methods ; Optic Disk/pathology ; },
abstract = {BACKGROUND: To cross-sectionally and longitudinally examine whether retinal vessel traits are associated with glaucoma-related outcomes (glaucoma, cup-to-disc ratio [CDR] and intraocular pressure [IOP]) and age-related macular degeneration (AMD).<br><br>METHODS: Baseline and 3-year follow-up data from the 30&#x2009;097 participants of the Canadian Longitudinal Study on Aging were used. The follow-up rate was 92%. QUARTZ, a deep learning algorithm, was used to extract data from retinal images including arteriolar and venular diameter, tortuosity and vertical CDR. Glaucoma and AMD were self-reported. IOP was measured. Multiple linear and logistic regression were used to adjust for demographic, lifestyle and clinical factors.<br><br>RESULTS: Having wider arterioles was associated with a lower odds of glaucoma (OR&#x2009;=&#x2009;0.36, 95% CI: 0.20, 0.65) at baseline but there was no association using longitudinal data. Instead, glaucoma at baseline was strongly associated with 3-year change in arteriolar diameter (&#x3b2;&#x2009;=&#x2009;-0.21, 95% CI: -0.37, -0.05) indicating that the cross-sectional association may have been due to reverse causality. Using longitudinal data, greater venular tortuosity was associated with a reduced 3-year development of glaucoma (OR&#x2009;=&#x2009;0.52, 95% CI: 0.31, 0.87) and a 3-year reduction in the CDR (&#x3b2;&#x2009;=&#x2009;-0.006, 95% CI: -0.010, -0.002). Wider venular diameter was associated with a higher odds of AMD at baseline (OR&#x2009;=&#x2009;2.77, 95% CI: 1.50, 5.15) and a higher odds of the 3-year development of AMD (OR&#x2009;=&#x2009;4.15, 95% CI: 1.95, 8.82).<br><br>CONCLUSIONS: Understanding the temporal relationship of changes in the retinal microvasculature and the development of eye disease may lead to better treatment and prevention strategies.},
}
@article {pmid40515543,
year = {2025},
author = {Ly, A and Herse, S and Williams, MA and Stapleton, F},
title = {Artificial intelligence for age-related macular degeneration diagnosis in Australia: A Novel Qualitative Interview Study.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {6},
pages = {1282-1292},
pmid = {40515543},
issn = {1475-1313},
support = {//Roche Products, Australia/ ; },
mesh = {Humans ; *Artificial Intelligence ; Australia/epidemiology ; *Macular Degeneration/diagnosis/epidemiology ; Qualitative Research ; Interviews as Topic ; Female ; Male ; },
abstract = {INTRODUCTION: Artificial intelligence (AI) systems for age-related macular degeneration (AMD) diagnosis abound but are not yet widely implemented. AI implementation is complex, requiring the involvement of multiple, diverse stakeholders including technology developers, clinicians, patients, health networks, public hospitals, private providers and payers. There is a pressing need to investigate how AI might be adopted to improve patient outcomes. The purpose of this first study of its kind was to use the AI translation extended version of the non-adoption, abandonment, scale-up, spread and sustainability of healthcare technologies framework to explore stakeholder experiences, attitudes, enablers, barriers and possible futures of digital diagnosis using AI for AMD and eyecare in Australia.<br><br>METHODS: Semi-structured, online interviews were conducted with 37 stakeholders (12 clinicians, 10 healthcare leaders, 8 patients and 7 developers) from September 2022 to March 2023. The interviews were audio-recorded, transcribed and analysed using directed and summative content analysis.<br><br>RESULTS: Technological features influencing implementation were most frequently discussed, followed by the context or wider system, value proposition, adopters, organisations, the condition and finally embedding the adaptation. Patients preferred to focus on the condition, while healthcare leaders elaborated on organisation factors. Overall, stakeholders supported a portable, device-independent clinical decision support tool that could be integrated with existing diagnostic equipment and patient management systems. Opportunities for AI to drive new models of healthcare, patient education and outreach, and the importance of maintaining equity across population groups were consistently emphasised.<br><br>CONCLUSIONS: This is the first investigation to report numerous, interacting perspectives on the adoption of digital diagnosis for AMD in Australia, incorporating an intentionally diverse stakeholder group and the patient voice. It provides a series of practical considerations for the implementation of AI and digital diagnosis into existing care for people with AMD.},
}
@article {pmid40514020,
year = {2025},
author = {Coletto, A and Serafino, S and Olivieri, C and Marica, V and Viggiano, P and Vallino, V and Marolo, P and Borrelli, E and Reibaldi, M},
title = {Macular fibrosis in neovascular AMD: inter-reader and intermodality variability across four imaging modalities.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {6},
pages = {e906-e914},
doi = {10.1016/j.jcjo.2025.05.019},
pmid = {40514020},
issn = {1715-3360},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; Prospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Fibrosis/diagnosis ; *Macula Lutea/pathology ; Fluorescein Angiography/methods ; Aged, 80 and over ; Reproducibility of Results ; Observer Variation ; Middle Aged ; Fundus Oculi ; },
abstract = {OBJECTIVE: To assess inter-reader and intermodality variability in quantifying macular fibrosis in patients with neovascular age-related macular degeneration (AMD) using 4 imaging modalities: color fundus photography (CFP), near-infrared reflectance (NIR), structural optical coherence tomography (OCT), and MultiColor imaging.<br><br>DESIGN: Prospective, cross-sectional case series.<br><br>PARTICIPANTS: Thirty eyes of 30 patients with neovascular AMD and macular fibrosis, previously treated with anti-vascular endothelial growth factor therapy.<br><br>METHODS: Imaging was performed using CFP, NIR, structural OCT, and MultiColor modalities. Two masked graders evaluated the size of macular fibrosis using each modality. The study assessed inter-reader agreement using the intraclass correlation coefficient (ICC), coefficient of variation (CV), and 95% coefficient of repeatability. Intermodality variability was analyzed using repeated measures ANOVA and pairwise comparisons.<br><br>RESULTS: Structural OCT demonstrated the highest inter-reader agreement (ICC&#x202f;=&#x202f;0.983; CV&#x202f;=&#x202f;0.04), while NIR exhibited the lowest (ICC&#x202f;=&#x202f;0.461; CV&#x202f;=&#x202f;0.26). The median macular fibrosis size was largest on structural OCT (4.87 mm&#xb2;) and smallest on MultiColor imaging (2.03 mm&#xb2;). Significant differences were observed between imaging modalities, with fibrosis measurements from different modalities not consistently comparable.<br><br>CONCLUSIONS: Structural OCT is the most reliable modality for quantifying macular fibrosis in neovascular AMD. The observed intermodality variability highlights the need for standardized criteria in fibrosis assessment across imaging techniques, as differences can impact clinical interpretation and management.},
}
@article {pmid40512945,
year = {2025},
author = {Gupta, AK and Meng, R and Duelk, M and Wald, K and Srinivasan, VJ},
title = {High-resolution visible light OCT of the human retina with combined superluminescent diodes.},
journal = {Optics letters},
volume = {50},
number = {12},
pages = {4070-4073},
pmid = {40512945},
issn = {1539-4794},
support = {P41 EB032840/EB/NIBIB NIH HHS/United States ; OT2 OD038130/OD/NIH HHS/United States ; R01 EY031469/EY/NEI NIH HHS/United States ; R01 EB035762/EB/NIBIB NIH HHS/United States ; R01 EY036192/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/instrumentation/methods ; *Retina/diagnostic imaging ; *Light ; *Semiconductors ; },
abstract = {High-resolution optical coherence tomography (OCT) requires broadband, spatially coherent light sources. Today, the source of choice for visible light OCT, the supercontinuum (SC), is bulky, expensive, and prone to excess noise. Here we demonstrate high-resolution visible light OCT of the human retina with a combined superluminescent diode (SLD) source. The source is longer in wavelength than the high blue light hazard range but shorter in wavelength than the high photopic efficiency range, ensuring subject safety and comfort. We report an axial resolution of 3.2 µm in the retina. We find that Bruch's membrane is well-delineated in subjects without ocular pathology, even though the axial resolution is ∼3× coarser than SC visible light OCT. Imaging of intermediate age-related macular degeneration is also shown. Within the cyan-green wavelength range of the SLD, optical density spectra resemble those of macular pigments. While the combined SLD approach does not achieve the micrometer-scale resolution of the SC, it potentially reduces the cost and complexity of visible light OCT while providing novel disease-relevant biomarkers, to the best of our knowledge, in human retina.},
}
@article {pmid40512794,
year = {2025},
author = {Toomey, CB and Pflugmacher, S and Park, K and Pihl, J and Weiser Novak, S and Rodriguez, J and Jalali, M and Jung, J and Mozafari, M and Omran, SP and Pormir, CK and Hauer, J and Painter, C and Walker, E and Huang, AS and Boassa, D and Handa, JT and Aastrup, T and Gordts, PLSM and Esko, JD},
title = {Bruch's membrane heparan sulfate retains lipoproteins in the early stages of age-related macular degeneration.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {24},
pages = {e2500727122},
pmid = {40512794},
issn = {1091-6490},
support = {R01 EY035805/EY/NEI NIH HHS/United States ; RMF-IRRF-001-2022//International Retinal Research Foundation (IRRF)/ ; EY024225//HHS | NIH | National Eye Institute (NEI)/ ; Unrestricted Grant//Research to Prevent Blindness (RPB)/ ; CD-CL-0824-0886-UCSD//Foundation Fighting Blindness (FFB)/ ; EY030501//HHS | NIH | National Eye Institute (NEI)/ ; HL131474//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; unrestricted grant//Research to Prevent Blindness (RPB)/ ; 30342012//Novartis AG | Alcon | Alcon Research Institute (ARI)/ ; EY035322//HHS | NIH | National Eye Institute (NEI)/ ; EY033765//HHS | NIH | National Eye Institute (NEI)/ ; RPB CDA 2023//Research to Prevent Blindness (RPB)/ ; EY031594//HHS | NIH | National Eye Institute (NEI)/ ; A-013//Larry L. Hillblom Foundation (LLHF)/ ; R01 EY031594/EY/NEI NIH HHS/United States ; K08 EY035322/EY/NEI NIH HHS/United States ; K12 EY024225/EY/NEI NIH HHS/United States ; R21 AI185519/AI/NIAID NIH HHS/United States ; R01 EY030501/EY/NEI NIH HHS/United States ; P01 HL131474/HL/NHLBI NIH HHS/United States ; EY035805//HHS | NIH | National Eye Institute (NEI)/ ; R01 EY033765/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Heparitin Sulfate/metabolism ; *Macular Degeneration/metabolism/pathology ; *Bruch Membrane/metabolism/pathology/ultrastructure ; *Lipoproteins/metabolism ; Aged ; Aged, 80 and over ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Lipoprotein retention in Bruch's membrane is a key event in the pathobiology of early and intermediate age-related macular degeneration (AMD). However, the mechanism of lipoprotein retention in BrM is unknown. Given the established role of glycosaminoglycans (GAG) in binding lipoproteins, our laboratory sought to determine the role of GAGs in AMD BrM. In this study, BrM GAG content in AMD pathobiology was analyzed in human postmortem tissue. Strikingly, increased levels of highly sulfated heparan sulfate were present in AMD Bruch's membrane as compared to non-AMD samples. In addition, using scanning electron microscopy of postmortem AMD tissue, we show aggregates of lipoprotein-like particles on the retinal pigmented epithelium side of Bruch's membrane adjacent to heparan sulfate. We also show that heparin displaces lipoproteins rich in apolipoprotein A1 from human BrM, suggesting their identity as high-density lipoproteins. Using human BrM immobilized to quartz crystal microbalance biosensor (QCM) chips, we show that heparan sulfate is required for lipoprotein binding to BrM and soluble heparan sulfate can remove lipoproteins bound to BrM. Thus, our data establish that heparan sulfate regulates lipoprotein deposition in AMD BrM. These findings provide a foundation for targeted therapies capable of either preventing lipoprotein accumulation or removing drusen in the early and intermediate stages of AMD prior to vision loss.},
}
@article {pmid40512487,
year = {2025},
author = {Ulla, L and Foti, C and Arrigo, A and Battaglia Parodi, M and Cicinelli, MV and Marolo, P and Miserocchi, E and Peronetti, M and Bandello, F and Borrelli, E and Reibaldi, M},
title = {Choroidal Hyperreflective Foci Represent a Common Finding Across Different Types of Macular Atrophy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {42},
pmid = {40512487},
issn = {1552-5783},
mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Female ; Male ; Middle Aged ; *Choroid/pathology ; Aged ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/complications ; Adult ; *Geographic Atrophy/diagnosis ; *Macula Lutea/pathology ; Aged, 80 and over ; Visual Acuity ; Fundus Oculi ; *Choroid Diseases/diagnosis ; },
abstract = {PURPOSE: To evaluate the presence, distribution, and potential implications of choroidal hyperreflective foci (HRFs) across different types of macular atrophy and their relationship with the size of atrophic regions.<br><br>METHODS: This retrospective case series analyzed 95 eyes from 87 patients with macular atrophy caused by various conditions, including geographic atrophy due to age-related macular degeneration, pachychoroid disease, punctate inner choroidopathy, angioid streaks, and Stargardt disease. Structural optical coherence tomography (OCT) images were evaluated to identify HRFs in different choroidal layers. HRF counts were correlated with the size of macular atrophy and underlying conditions using multiple regression analysis.<br><br>RESULTS: HRFs were observed in all cases, with their number significantly associated with the size of macular atrophy (P < 0.001). The highest HRF counts were found in Stargardt disease, while the lowest were in pachychoroid disease. However, no association was identified between HRF quantity and specific disease type (P = 0.2). HRFs were primarily located in the choriocapillaris, Sattler's layer, and near Bruch's membrane but were absent within choroidal vessels.<br><br>CONCLUSIONS: HRFs represent a common OCT finding in various disorders associated with macular atrophy. Their quantity correlates with atrophy size rather than disease type, suggesting they are likely normal choroidal components rendered visible by RPE loss. Future studies are warranted to elucidate their origin and potential implications for disease progression.},
}
@article {pmid40512437,
year = {2025},
author = {Brandl, C and Heid, IM and Helbig, H and Holz, FG and Finger, RP and Mauschitz, MM},
title = {[Risk factors for age-related macular degeneration : Lessons learned from current data].},
journal = {Die Ophthalmologie},
volume = {122},
number = {7},
pages = {510-517},
pmid = {40512437},
issn = {2731-7218},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Genetic Predisposition to Disease/epidemiology/genetics ; *Macular Degeneration/epidemiology/prevention &amp; control/genetics ; Prevalence ; Risk Factors ; *Smoking/epidemiology/adverse effects ; },
abstract = {BACKGROUND: Identifying risk factors for age-related macular degeneration (AMD) is crucial for patient counseling and the development of potential prevention strategies.<br><br>OBJECTIVES: This study summarizes the current epidemiological evidence on AMD risk factors, analyzes their clinical relevance, and discusses potential preventive measures.<br><br>MATERIALS AND METHODS: A&#xa0;systematic literature review was conducted to assess demographic, genetic, and modifiable risk factors for AMD, including smoking, diet, and physical activity.<br><br>RESULTS: Age is the strongest risk factor for early and advanced AMD. Genetic predisposition also plays a&#xa0;critical role, particularly from genetic variants in the complement and lipid metabolism pathways and extracellular matrix. Modifiable factors such as smoking, dietary habits, and physical activity significantly influence the risk of AMD. Recent studies further suggest a&#xa0;potentially beneficial effect of medication intake, such as metformin and statins.<br><br>CONCLUSION: Epidemiological data indicate that smoking cessation, adherence to a&#xa0;Mediterranean diet, and regular physical activity are associated with a&#xa0;reduced risk of AMD over time. These factors should be integral to patient counseling. The continued extension of longitudinal study data will be key to refining individual risk profiles and optimizing prevention strategies.},
}
@article {pmid40512025,
year = {2025},
author = {Agostini, H and Baumane, K and Balčiūnienė, VJ and Ozols, K and Soni, R and Hamdi, S and Cirillo, S and Rai, M and Otto, H and Leutz, S and Sattar, A and Berti, F},
title = {A randomized, double-masked parallel-group, multicenter clinical study evaluating the efficacy and safety of the biosimilar candidate AVT06 compared to the reference product aflibercept in participants with neovascular age-related macular degeneration.},
journal = {Expert opinion on biological therapy},
volume = {25},
number = {7},
pages = {773-787},
doi = {10.1080/14712598.2025.2519531},
pmid = {40512025},
issn = {1744-7682},
mesh = {Humans ; Double-Blind Method ; *Recombinant Fusion Proteins/adverse effects/pharmacokinetics/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Biosimilar Pharmaceuticals/adverse effects/pharmacokinetics/administration &amp; dosage/therapeutic use ; Male ; Female ; Aged ; Visual Acuity/drug effects ; Intravitreal Injections ; *Angiogenesis Inhibitors/adverse effects/pharmacokinetics/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Middle Aged ; Treatment Outcome ; *Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: This study compared efficacy, pharmacokinetics (PK), immunogenicity, and safety between AVT06, proposed biosimilar to reference product (RP) aflibercept (Eylea®), in participants with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: In this randomized, double-masked, multicenter, active-controlled trial, treatment na&#xef;ve participants received intravitreal injections of AVT06 or RP (2&#x2009;mg) over 48&#x2009;weeks. The primary endpoint was the change from baseline to Week 8 in best-corrected visual acuity (BCVA). Secondary endpoints included BCVA improvements and changes in Central Subfield Thickness (CST). PK, immunogenicity, and safety were also assessed.<br><br>RESULTS: The 90% and 95% confidence intervals (-0.60, 2.14 and -0.86, 2.40, respectively) in least squares mean difference in BCVA letter score from baseline to Week 8 were contained within the pre-specified equivalence margin of ETDRS BCVA letter score of [-3.5 to 3.5], supporting the demonstration of comparative efficacy. Secondary efficacy outcomes were also comparable. PK analyses supported systemic safety. There were no clinically meaningful differences in immunogenicity profiles. Safety profiles were similar; most treatment-emergent adverse events were mild and unrelated to the study drug.<br><br>CONCLUSIONS: Results supported a demonstration of comparable efficacy between AVT06 and RP aflibercept. Similar PK, immunogenicity, and safety profiles were also shown.<br><br>CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier is NCT05155293; ClinicalTrialsRegister.eu identifier is 2021-003651-42.},
}
@article {pmid40510741,
year = {2025},
author = {Ch, S and Lim, RR and Low, SWY and Grant, DG and Patterson, S and Ramasubramanian, A and Gadicherla, AK and Chaurasia, SS},
title = {A comprehensive overview of focused ion beam-scanning electron microscopy (FIB-SEM) applications for the evaluation of outer retina.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1586029},
pmid = {40510741},
issn = {2296-634X},
support = {R01 EY030077/EY/NEI NIH HHS/United States ; },
abstract = {The retina is the light-sensitive inner layer of the eye, consisting of multiple cell types organized into ten distinct layers of neurons interconnected by synapses that play a crucial role in visual function. Any pathological alterations in this intricate structure can lead to vision impairment. Conventional electron microscopy techniques, including scanning electron microscopy (SEM) and transmission electron microscopy (TEM), provide our current understanding of ultrastructural defects in the retina. However, they are limited by their inability to image the complex three-dimensional (3D) structure layer-by-layer at a nanoscale resolution. Advanced electron microscopy techniques, including serial block face scanning (SBF), have emerged as a superior alternative to traditional imaging methods for enhancing the understanding of 3D segmentation at the nanoscale and revealing the ultrastructural architecture of the retina under both physiological and pathological conditions. This article provides a comprehensive overview of the advancements in SBF electron microscopy, emphasizing focused ion beam (FIB)-SEM for studying the interdigitation zone (IZ), which connects the cone outer segments to the retinal pigment epithelium (RPE) to enhance the understanding of retinal degenerative diseases such as inherited retinal disorders (IRDs), age-related macular degeneration (AMD), and diabetic retinopathy (DR). We have collated and discussed current literature alongside our recent work on FIB-SEM applications, particularly in examining the structural integrity of the outer retina. FIB-SEM can bridge the knowledge gap between structural insights and functional impairments through its state-of-the-art imaging and 3D segmentation capabilities. Additionally, it offers various applications for the pathological evaluation of retinal degenerative diseases.},
}
@article {pmid40509232,
year = {2025},
author = {Lin, S and Guo, MS and Tang, RW and Ye, Y and Wu, J and Ho, YM and Duan, R and Leung, KW and Dong, TT and Tsim, KW},
title = {Design, Synthesis, and Biological Evaluations of a Novel Resveratrol-Type Analogue Against VEGF.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {11},
pages = {},
pmid = {40509232},
issn = {1420-3049},
support = {2019AG035//Zhongshan Municipal Bureau of Science and Technology/ ; T13-605/18-W//Hong Kong RGC Theme-based Research Scheme/ ; },
mesh = {*Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Resveratrol/analogs &amp; derivatives/pharmacology/chemistry/chemical synthesis ; Humans ; *Drug Design ; Signal Transduction/drug effects ; *Stilbenes/pharmacology/chemistry/chemical synthesis ; },
abstract = {Vascular endothelial growth factor (VEGF), also known as VEGF-A, has been reported to mediate various diseases, including cancer and wet age-related macular degeneration (wAMD). Despite the fact that VEGF inhibitors are commercially available and appear to be effective in clinical applications, adverse effects have been caused by these treatments. There is an unmet need for developing novel VEGF-targeted treatments against these diseases. Resveratrol, a phytochemical derived from fruits and vegetables, has shown promising potency in suppressing VEGF-mediated bioactivities through a series of in vitro and in vivo testing models. Herein, we report that RE-1, a synthetic resveratrol-type analog, displays robust inhibitory activities against VEGF and its downstream signaling pathways, surpassing its parental molecule, resveratrol. In addition, the drug capabilities of RE-1 were evaluated. As a newly synthesized chemical, RE-1 could be considered for subsequent pharmacological development targeting VEGF-related diseases.},
}
@article {pmid40507802,
year = {2025},
author = {Callan, A and Heckman, J and Tah, G and Lopez, S and Valdez, L and Tsin, A},
title = {VEGF in Diabetic Retinopathy and Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {11},
pages = {},
pmid = {40507802},
issn = {1422-0067},
support = {R13 CA278054/CA/NCI NIH HHS/United States ; R15 EY033551/EY/NEI NIH HHS/United States ; CA278054/GF/NIH HHS/United States ; EY033551/GF/NIH HHS/United States ; DA056203/GF/NIH HHS/United States ; R13 DA056203/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *Diabetic Retinopathy/metabolism/drug therapy/pathology ; *Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; *Macular Degeneration/metabolism/drug therapy/pathology ; Animals ; Angiogenesis Inhibitors/therapeutic use ; Choroidal Neovascularization/metabolism ; },
abstract = {Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis throughout the human body, influencing countless physiological and pathological processes, including tumor growth, preeclampsia, and retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In DR, VEGF promotes retinal neovascularization and intraretinal fluid accumulation, leading to complications like diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Regular intravitreal anti-VEGF injections are commonly used to manage PDR and DME, though repeated treatments are often required, and efficacy can be limited. AMD, a major cause of vision loss in older adults, is characterized by either dry or wet forms. While the dry form has not been shown to be influenced by VEGF, the choroidal neovascularization of wet AMD has strong associations with VEGF. Current treatment for wet AMD consists primarily of anti-VEGF injections, the gold standard of care, but is limited by varying patient responses, as treatments are often repeated every 4-8 weeks indefinitely. This review explores the pathogenic role of VEGF in both DR and AMD, discussing the molecular mechanisms underlying these diseases and the therapeutic approaches targeting VEGF. Despite advancements, the variability in treatment responses highlights the need for continued research to develop more effective therapies to prevent vision loss and blindness associated with these retinal diseases.},
}
@article {pmid40507504,
year = {2025},
author = {Bakdalieh, A and Khawaja, LM and Yu, M},
title = {Dark Adaptometry as a Diagnostic Tool in Retinal Diseases: Mechanisms and Clinical Utility.},
journal = {Journal of clinical medicine},
volume = {14},
number = {11},
pages = {},
pmid = {40507504},
issn = {2077-0383},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; P30-EY025585/GF/NIH HHS/United States ; },
abstract = {Dark adaptometry is a non-invasive functional test that assesses the retina's ability to recover sensitivity in low-light conditions following photobleaching. This review explores the physiological mechanisms underlying dark adaptation (DA), including photopigment regeneration and the critical role of the retinal pigment epithelium in the visual cycle. We detail clinical protocols for dark adaptometry using modern instruments such as the AdaptDx, highlighting methodological advances that improve testing efficiency and reproducibility. The clinical utility of dark adaptometry is examined across a range of inherited and acquired retinal disorders, including age-related macular degeneration (AMD), retinitis pigmentosa (RP), Stargardt disease, diabetic retinopathy (DR), cone-rod dystrophy (CRD), vitamin A deficiency, and congenital stationary night blindness (CSNB). Dark adaptometry has emerged as a sensitive biomarker capable of detecting functional deficits before structural changes are evident, making it a valuable tool for early diagnosis and monitoring disease progression. However, limitations such as age-related variability, patient compliance, and lack of standardization remain challenges to broader clinical adoption. Continued refinement of dark adaptometry protocols and instrumentation is essential to maximize its diagnostic potential in ophthalmic practice.},
}
@article {pmid40507429,
year = {2025},
author = {Fieß, A and Gißler, S and Mildenberger, E and Pfeiffer, N and Hartmann, A and Schuster, AK},
title = {Long-Term Ocular Outcomes of Prematurity: Morphological Alterations, Visual Aspects and Implications for Age-Related Ocular Diseases.},
journal = {Journal of clinical medicine},
volume = {14},
number = {11},
pages = {},
pmid = {40507429},
issn = {2077-0383},
support = {//Ernst und Berta Grimmke-Stiftung/ ; //Else Kr&#xf6;ner-Fresenius-Stiftung/ ; },
abstract = {The impact of prematurity has been reported to affect ocular development during infancy and childhood. Research into long-term ocular outcomes in adults born preterm is highly relevant due to a possible impact on the development of age-related ocular diseases such as macular degeneration. The aim was to review the currently available literature regarding outcomes of prematurity on ocular morphology in adults to provide a summary of the long-term effects of prematurity and associated factors such as low birth weight (BW) and retinopathy of prematurity (ROP) and its treatment. Adults formerly born preterm have a higher prevalence of refractive error, lower visual acuity, a higher prevalence of strabismus, shorter axial length, a steeper corneal radius, increased macular thickness, and a thinner peripapillary retinal nerve fiber layer thickness (RNFL), as well as changes in vessel anatomy and the foveal avascular zone. Adults who suffered from ROP have a high risk of myopic refractive error, amblyopia, shallower anterior chambers and thicker crystalline lenses, higher corneal aberrations, thinner RNFL thickness, and foveal hypoplasia. Individuals with advanced ROP requiring treatment also have higher rates of astigmatism, an increased temporal RNFL thickness, altered macular curvature, and reduced visual acuity. Prematurity leads to lifelong ocular morphological and functional changes, suggesting that fetal origins may contribute to age-related ocular diseases. This could have implications for ophthalmologic monitoring and the frequency of check-ups in adulthood.},
}
@article {pmid40507384,
year = {2025},
author = {Di Pippo, M and Rullo, D and Maugliani, E and Lotery, AJ and Abdolrahimzadeh, S},
title = {Short-Term Morphological and Quantitative Changes in Non-Exudative Macular Neovascularization Using Spectral-Domain OCT and OCT Angiography: A Pilot Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {11},
pages = {},
pmid = {40507384},
issn = {2077-0383},
support = {RP12117A34924689//Sapienza University of Rome/ ; },
abstract = {Background/Objectives: The aim of the current investigation was to assess the short-term changes in retinal-choroidal vasculature and the morphological complexity of non-exudative macular neovascularization (NE-MNV) using optical coherence tomography angiography (OCTA) and spectral-domain optical coherence tomography (SD-OCT). Methods: Sixteen eyes of 12 patients with NE-MNV underwent baseline and six-month follow-up examinations, including comprehensive ophthalmological assessment and imaging. Central macular thickness, foveal avascular zone, vessel density, flow area, and choroidal vascularity index were analyzed. NE-MNV morphology was quantitatively assessed for area, vessel characteristics, and fractal dimensions. Results: Significant changes in NE-MNV morphology were noted over six months, especially in fractal dimensions, vessel junctions, and vessel length (p-values: 0.01, 0.037, and 0.036, respectively). While there was an increase in the NE-MNV area, it did not reach statistical significance. No significant changes were shown regarding the standard SD-OCT and OCTA output parameters or choroidal measurements. Conclusions: The increase in NE-MNV fractal dimensions suggests rising complexity in the neovascular network and may indicate possible implications for clinical management. The correlation between baseline and follow-up measures underscores a trend toward complexity, pointing to the necessity for closer monitoring of patients with higher NE-MNV fractal dimensions.},
}
@article {pmid40506954,
year = {2025},
author = {Gawęcki, M and Kiciński, K and Grzybowski, A and Teper, S},
title = {Posterior Vitreous Detachment in Healthy Versus AMD Eyes Assessed by Widefield Optical Coherence Tomography.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
pmid = {40506954},
issn = {2075-4418},
abstract = {Introduction: This study aimed to determine the frequency of posterior vitreous detachment (PVD) in dry and wet age-related macular degeneration (AMD) patients compared with healthy eyes via ultrawide field optical coherence tomography (UWF-OCT). Additionally, the retinal thicknesses in the central and peripheral zones of AMD patients and the control group were compared. Methods: We included 123 eyes from 83 participants with dry AMD, 123 from 87 participants with wet AMD, and 85 from 53 healthy controls. All three study groups were compared according to age, sex, best corrected visual acuity (BCVA), PVD stage, axial length, and retinal thickness in the central, perifoveal, and peripheral zones. Additional analyses included correlations between the BCVA and PVD stage and between retinal thickness and the PVD stage. Results: Complete separation of the vitreous from the macula was significantly more common in AMD patients than in the control group, as noted in 47 eyes (55.29%) in the control group, 92 eyes (74.80%) in the wet AMD group, and 93 eyes (75.61%) in the dry AMD group. The PVD stage did not significantly influence retinal thickness. BCVA in AMD patients did not correlate with the PVD stage. Conclusions: Complete PVD is more common in AMD patients than in healthy controls, as evaluated by UWF-OCT. No relationship between the PVD stage and AMD type or BCVA was observed.},
}
@article {pmid40506926,
year = {2025},
author = {Yim, AC and Azzouz, L and Paulus, YM},
title = {Novel Handheld Device for Remote Monitoring of Dry Macular Degeneration and Patient Usability Assessment.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
pmid = {40506926},
issn = {2075-4418},
support = {1R01EY034325-23A1/NH/NIH HHS/United States ; R01 EY034325/EY/NEI NIH HHS/United States ; 1K08EY027458-18A1/NH/NIH HHS/United States ; FFSGIA16002//Fight for Sight/ ; K08 EY027458/EY/NEI NIH HHS/United States ; unrestricted departmental support//Research to Prevent Blindness/ ; },
abstract = {Background/Objectives: A novel, handheld, standalone device using shape discrimination hyperacuity has been developed to remotely monitor age-related macular degeneration (AMD). Methods: We clinically validated the device in an outpatient dry AMD population to evaluate its usability and comfort. A cross-sectional study was conducted with subjects aged 50 years or older with dry AMD at the University of Michigan Kellogg Eye Center outpatient clinic after approval from the UM IRB (HUM00187177). Subjects used the device and then completed a device survey and System Usability Scale (SUS). Results: Thirty-one subjects completed the study, and one subject withdrew post-study completion (mean age 77 years, STD 8 years). The mean testing time was 126 s (STD 56 s), and the median was 116 s. Most patients reported that the use of the device occurred for an acceptable duration (97%), was easy (97%), and was comfortable (90%). The mean SUS score was 77.7 (STD 11.9). Conclusions: A handheld, standalone device can provide a rapid, easy, and comfortable testing solution for patients with dry AMD. The usability of the device supports further clinical trials to demonstrate the device's ability to reliably detect the progression of AMD.},
}
@article {pmid40505850,
year = {2025},
author = {Dhoot, DS},
title = {Treatment of Retinal/Choroidal Vascular Diseases by Sustained Delivery of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors.},
journal = {American journal of ophthalmology},
volume = {277},
number = {},
pages = {570-579},
doi = {10.1016/j.ajo.2025.06.010},
pmid = {40505850},
issn = {1879-1891},
mesh = {Animals ; Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Choroid Diseases/drug therapy ; Delayed-Action Preparations ; Drug Delivery Systems ; Intravitreal Injections ; *Protein Kinase Inhibitors/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors ; *Retinal Diseases/drug therapy ; Tyrosine Kinase Inhibitors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: To review current investigational strategies using sustained delivery of vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (TKIs) for the treatment of retinal and choroidal vascular diseases.<br><br>DESIGN: Narrative review.<br><br>METHODS: A comprehensive review of preclinical and clinical studies evaluating the safety, efficacy, and durability of VEGF receptor TKIs delivered via sustained-release platforms, including intravitreal hydrogel implants, suprachoroidal injections, subcutaneous delivery systems, and oral formulations.<br><br>RESULTS: Multiple VEGF receptor TKIs, including axitinib, sunitinib, vorolanib, and dendranib, are under evaluation for sustained treatment of neovascular age-related macular degeneration, diabetic macular edema, and diabetic retinopathy. Delivery platforms such as bioerodible implants (OTX-TKI/axitinib, EYP-1901/vorolanib), suprachoroidal injections (CLS-AX/axitinib), microparticle suspensions (GB-102/sunitinib), and oral or subcutaneous therapies (X-82, D-4517.2) have demonstrated variable degrees of treatment durability, reduction in anti-VEGF injection burden, and maintenance of anatomic and functional outcomes in early phase studies. Safety profiles have generally been favorable, although certain formulations showed dose-dependent adverse effects.<br><br>CONCLUSIONS: Sustained delivery of VEGF receptor TKIs represents a promising therapeutic paradigm for retinal and choroidal vascular diseases, potentially reducing treatment burden while maintaining efficacy. Continued evaluation through larger, controlled clinical trials is essential to validate these early findings and define the role of these agents in clinical practice.},
}
@article {pmid40504540,
year = {2025},
author = {Lynch, AM and Grove, NC and Wagner, BD and Palestine, AG and Holers, VM and Frazer-Abel, AA and Gnanaraj, R and Lisker-Cervantes, A and Patnaik, JL and de Carlo Forest, TE and Auer, EA and McReynolds, AJ and Mathias, MT and Manoharan, N and Rodriquez De Cordoba, S and Mandava, N},
title = {Dynamic Risk of Systemic Complement Activation With Time to Progression to Advanced Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {143},
number = {8},
pages = {634-642},
pmid = {40504540},
issn = {2168-6173},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; Disease Progression ; Aged ; *Complement Activation/physiology ; Follow-Up Studies ; *Wet Macular Degeneration/diagnosis/blood ; Aged, 80 and over ; Risk Factors ; *Geographic Atrophy/diagnosis/blood ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; },
abstract = {IMPORTANCE: Understanding the relationship between longitudinally measured systemic complement factors and intermediate AMD (iAMD) progression may enable the introduction of systemic therapeutics earlier in the disease course, before vision loss occurs.<br><br>OBJECTIVE: To determine the contribution of longitudinal measures of systemic complement factors and ratios to time to progression to advanced AMD (geographic atrophy [GA] or neovascular AMD [NVAMD]).<br><br>This cohort study was conducted at Sue Anschutz Rodgers Eye Center, Aurora, Colorado, from 2014 to 2022. Participants were patients with iAMD and at least 1 month of follow-up. Data analysis was performed from September to December 2024.<br><br>EXPOSURES: Complement factors.<br><br>MAIN OUTCOMES AND MEASURES: Time to progression to advanced AMD, either GA or NVAMD. Joint models were used to estimate the relationship between the exposures and the outcomes. The hazard ratio (HR) was a measure of association.<br><br>RESULTS: Among 325 participants, the mean (SD) age was 76 (7.0) years; 212 participants (65%) were female and 113 (35%) male. During the 8-year follow-up period (mean, 3.9 years), 110 participants (34%) progressed to any advanced AMD. Sixty-four participants (20%) progressed to GA and 46 (14%) to NVAMD. Higher systemic levels of C4 (HR, 6.8; 95% credible interval [CrI], 1.7-26.2; P&#x2009;=&#x2009;.03), C4b (HR, 60.4; 95% CrI, 6.5-544; P&#x2009;<&#x2009;.001), C3a/C3 (HR, 49.4; 95% CrI, 5.2-675; P&#x2009;<&#x2009;.001), C5a/C5 (HR, 29.3; 95% CrI, 4.8-258; P&#x2009;<&#x2009;.001), sC5b-9/C5 (HR, 297; 95% CrI, 10-14&#x202f;877; P&#x2009;=&#x2009;.003), and factor I (HR, 525.9; 95% CrI, 5.5-107&#x202f;589; P&#x2009;=&#x2009;.02) were associated with shorter time to progression to any AMD. Levels of C3a/C3 (HR, 9.5; 95% CrI, 1.9-55.9; P&#x2009;=&#x2009;.01) and C5a/C5 (HR, 28.6; 95% CrI, 5.7-157.9; P&#x2009;<&#x2009;.001) were associated with the hazard of GA.<br><br>CONCLUSIONS AND RELEVANCE: Continued dysregulation of complement pathways appears to increase the hazard of iAMD progression. This supports the possibility of identifying a high-risk group of patients with iAMD for personalized ophthalmic care and targeted treatments to attenuate the risk of iAMD progression.},
}
@article {pmid40504425,
year = {2025},
author = {Yanagi, Y and Mori, R and Teo, KYC and Park, KH and Ngah, NF and Chen, SJ and Ruamviboonsuk, P and Kondo, N and Lee, WK and Rajagopalan, R and Obata, R and Wong, IYH and Chee, C and Terasaki, H and Sekiryu, T and Chen, SC and Lai, TYY and Cheung, G and Honda, S},
title = {Six-year findings of polypoidal choroidal vasculopathy in the EVEREST II study: Japanese subgroup analysis.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {6},
pages = {894-901},
pmid = {40504425},
issn = {1613-2246},
support = {NMRC/LCG/004/2018//National Medical Research Council Singapore Open Fund Large Collaborative Grant/ ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Choroid/blood supply ; *Choroid Diseases/drug therapy/diagnosis/epidemiology ; Cross-Sectional Studies ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Japan/epidemiology/ethnology ; *Photochemotherapy/methods ; Photosensitizing Agents/therapeutic use ; Polypoidal Choroidal Vasculopathy ; *Polyps/drug therapy/diagnosis/epidemiology ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Time Factors ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Verteporfin ; *Visual Acuity ; East Asian People/statistics &amp; numerical data ; },
abstract = {PURPOSE: To evaluate long-term outcomes for polypoidal choroidal vasculopathy (PCV) in Japanese patients in the EVEREST II study.<br><br>STUDY DESIGN: A multicenter, cross-sectional study of the long-term outcomes of a cohort of patients originally treated with ranibizumab alone (monotherapy group) or in combination with photodynamic therapy PDT (combination group) in the EVEREST II study (ClinicalTrials.gov identifier, NCT01846273).<br><br>METHODS: Ninety participants from the six-year EVEREST II follow-up: 20 Japanese and 70 non-Japanese were included. Long-term changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were reported in the Japanese compared to non-Japanese participants. Number of injections, types of anti-vascular endothelial growth factor (VEGF) agents used, and cases with equal visits and injections, indicating fixed dosing or treat-and-extend (TAE) administration were investigated. Outcomes were also compared between those who had verteporfin PDT during the six-year period (n=14) and those who did not (n=6).<br><br>RESULTS: The Japanese and non-Japanese participants had similar baseline characteristics. The mean age for Japanese participants was 76&#xb1;4.47 years, with 25% being women. BCVA improved from baseline to year 2 in both groups (P < 0.05). At six years, BCVA was maintained in the Japanese (67.2 ETDRS letters) but decreased in the non-Japanese participants (from 68.8 to 53.5 letters). The Japanese participants received more injections than the non-Japanese (12.5 vs. 7.57, P=0.017). Aflibercept was the most frequently used anti-VEGF agent, and the number of fixed dosing or TAE administration was higher in the Japanese participants. No significant differences were found in functional and anatomical outcomes between those who received PDT and those who did not (all P > 0.05). However, non-PDT participants had numerically worse BCVA at the final visit.<br><br>CONCLUSIONS: This study highlights positive long-term outcomes for Japanese PCV patients and underscores the need for further research to validate these findings in broader patient populations.},
}
@article {pmid40504424,
year = {2025},
author = {Lee, SH and Lee, MY},
title = {Factors determining timing of first recurrence after three loading aflibercept injections in newly diagnosed neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {6},
pages = {876-885},
pmid = {40504424},
issn = {1613-2246},
mesh = {Humans ; Retrospective Studies ; Female ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; Fluorescein Angiography/methods ; Aged ; *Visual Acuity ; Recurrence ; Fundus Oculi ; Follow-Up Studies ; Aged, 80 and over ; Time Factors ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; },
abstract = {PURPOSE: To investigate factors affecting timing of the first recurrence after three loading aflibercept injections in patients with newly diagnosed neovascular age-related macular degeneration (NAMD).<br><br>STUDY DESIGN: Retrospective chart review.<br><br>METHODS: A retrospective study was conducted on 193 eyes from 193 patients newly diagnosed with NAMD who received monthly three loading aflibercept injections and a fourth injection by pro-re-nata therapy regimen for recurrence between January 2016 and May 2023. Recurrence was defined as reaccumulation of subretinal or intraretinal fluid or new or increased retinal or subretinal hemorrhage. Patients were divided into two groups. One group received a fourth injection within 12 weeks after the third dose of aflibercept (Group A) and the other group received a fourth injection after 12 weeks (Group B).<br><br>RESULTS: In group A (65 eyes) compared to group B (128 eyes), the frequency of polypoidal choroidal vasculopathy (PCV) was higher (60.0%: 36.7%), the frequency of retinal angiomatous proliferation was lower (6.2%: 18.0%), and the optical coherence tomography (OCT) findings showed that pigment epithelial detachment (PED) of hollow type was more likely to be observed compared to solid type (OR=3.14, p=0.013) or mixed type (OR=3.67, p=0.003) of PED; sharply peaked PED was more common (OR=2.05, p=0.045) and less likely to be seen in females (OR=0.46, p=0.034).<br><br>CONCLUSION: In patients with newly diagnosed NAMD who received three injection loading doses of aflibercept, earlier recurrence was predicted when PCV was present, when a hollow type of PED was observed on OCT, and when the patient was a man.},
}
@article {pmid40503367,
year = {2025},
author = {Sorrentino, FS and Parmeggiani, F and Gardini, L and Fontana, L and Musa, M and Gagliano, C and Zeppieri, M},
title = {Stem cell therapy for retinal pigment epithelium disorders.},
journal = {World journal of stem cells},
volume = {17},
number = {5},
pages = {103100},
pmid = {40503367},
issn = {1948-0210},
abstract = {Retinal pigment epithelium (RPE) dysfunction is involved in the advancement of numerous degenerative retinal illnesses, such as age-related macular degeneration and hereditary retinal abnormalities. Transplantation of RPE produced from stem cells has emerged as a promising therapeutic strategy to restore retinal function and prevent vision loss. However, other obstacles impede its clinical application, including immunological rejection, cell viability, functional integration, and the necessity for consistent differentiation techniques. This review offers a thorough examination of the molecular processes regulating RPE integrity, investigates recent progress in stem cell-derived RPE therapeutics, and addresses significant challenges to their broad implementation. Furthermore, we emphasize prospective avenues intended to enhance the safety, efficacy, and enduring success of RPE transplantation in clinical environments.},
}
@article {pmid40503074,
year = {2025},
author = {Medoro, A and Davinelli, S and Scuderi, L and Scuderi, G and Scapagnini, G and Fragiotta, S},
title = {Targeting Senescence, Oxidative Stress, and Inflammation: Quercetin-Based Strategies for Ocular Diseases in Older Adults.},
journal = {Clinical interventions in aging},
volume = {20},
number = {},
pages = {791-813},
pmid = {40503074},
issn = {1178-1998},
mesh = {Humans ; *Quercetin/pharmacology/therapeutic use/administration &amp; dosage ; *Oxidative Stress/drug effects ; *Antioxidants/therapeutic use/pharmacology ; Inflammation/drug therapy ; Aged ; *Eye Diseases/drug therapy ; *Cellular Senescence/drug effects ; Macular Degeneration/drug therapy ; Aging ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Drug Delivery Systems ; Neuroprotective Agents/pharmacology/therapeutic use ; },
abstract = {Quercetin, a flavonol abundant in fruits and vegetables, has attracted significant attention for its senotherapeutic effects, which involve the selective elimination of senescent cells and the modulation of pro-inflammatory phenotypes that contribute to age-related dysfunctions. These actions, together with its antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties, make quercetin a promising strategy for ocular diseases associated with visual impairment in older adults such as age-related macular degeneration, cataract, diabetic retinopathy, and glaucoma. This review emphasizes the mechanisms by which quercetin exerts its protective effects, with particular attention to its ability to target cellular senescence, reduce oxidative stress, and modulate inflammation. Despite extensive preclinical evidence, the clinical application of quercetin remains limited due to challenges related to poor bioavailability, rapid degradation, and the absence of standardized ocular formulations. Progress in drug delivery systems, including nanoparticles, nanoemulsions, and solid lipid carriers, provides promising strategies to overcome these barriers. In addition, combining quercetin with established treatments, such as anti-vascular endothelial growth factor (VEGF) agents and neuroprotective drugs, may enhance its therapeutic potential in managing and possibly reversing age-related ophthalmic disorders.},
}
@article {pmid40502295,
year = {2025},
author = {Liu, TYA and Liu, Y and Gastonguay, MS and Midgett, D and Kuo, N and Zhao, Y and Ullah, K and Alexander, G and Hartman, T and Koseoglu, ND and Jones, C},
title = {Predicting Imminent Conversion to Exudative Age-Related Macular Degeneration Using Multimodal Data and Ensemble Machine Learning.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100785},
pmid = {40502295},
issn = {2666-9145},
abstract = {OBJECTIVE: Exudative age-related macular degeneration (eAMD) is a major cause of central vision loss. Identifying patients at high risk of imminent eAMD could enable timely treatment and improve outcomes. Our goal was to develop and compare classical machine learning (ML) and deep learning (DL) models to predict imminent eAMD conversion within 6 months and integrate OCT with clinical data into a single predictive model.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients seen at the Wilmer Eye Institute between 2013 and 2021 with eAMD in &#x2265;1 eye.<br><br>METHODS: Spectral domain OCT volumes prior to conversion and the corresponding clinical data (age, best-corrected visual acuity, sex, and fellow-eye status) were collected and used for model training or testing. ResNet-50 and classical ML (Random Forest and XGBoost) models were trained to predict imminent conversion to eAMD within 6 months on an eye level. For the multilayer perceptron (MLP) framework, the trained ResNet-50 model was used as the feature encoder, and a downsampled feature vector concatenated with corresponding clinical tabular data was passed through the MLP (prediction head). Data were partitioned at the patient level (75% training, 15% validation, and 10% testing). Model performance was evaluated using the area under the operating characteristic curve (AUC) and 95% confidence interval (CI) for the model AUC was calculated using the percentile method after bootstrapping the test set 10 000 times. Model comparisons were made using modified paired t test. P < 0.05 was considered statistically significant.<br><br>MAIN OUTCOME MEASURES: Area under the operating characteristic curve.<br><br>RESULTS: Thirty-three thousand one hundred eighty-nine OCT volumes from 2084 patients (63% female; 89.1% White, 4.8% Black, and 2.3% Asian) were included. The mean age at the time of first-eye conversion was 78.9 (&#xb1; 9.3) years. Our best-performing models, "MLP multimodal" (trained with both OCT and clinical data; AUC: 0.76, 95% CI: 0.71-0.80) and "CNN OCT" (trained with only OCT data; AUC: 0.75, 95% CI: 0.70-0.79), had a DL (ResNet-50) architecture; "MLP multimodal" outperformed "CNN OCT" in predicting both all-eye (P < 0.05) and first-eye conversion (P < 0.001).<br><br>CONCLUSIONS: The 3-dimensional DL models, trained with OCT volumes, are capable of predicting both first-eye and fellow-eye imminent conversion to eAMD. The addition of clinical data further improved the model performance. These models, if validated prospectively, could serve as screening tools and allow retinal specialists to prioritize patients with more acute retinal issues.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40502292,
year = {2025},
author = {Terao, R and Aoki, S and Kitamoto, K and Totani, K and Yamanari, M and Sugiyama, S and Inoue, T and Obata, R and Azuma, K},
title = {Quantification of Hyperreflective Foci in Age-related Macular Degeneration by Polarization-Sensitive OCT.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100792},
pmid = {40502292},
issn = {2666-9145},
abstract = {PURPOSE: To quantify hyperreflective foci (HRF) using polarization-sensitive OCT (PS-OCT) and evaluate the effect of anti-VEGF therapy on HRF reduction.<br><br>DESIGN: Retrospective study.<br><br>SUBJECTS: Twelve eyes from 12 patients with neovascular age-related macular degeneration (nAMD) who underwent PS-OCT imaging before and after 4 intravitreal injections of faricimab, administered every 4 weeks.<br><br>METHODS: Retinal layers between the inner border of the inner nuclear layer and the outer border of the outer segment of photoreceptors were analyzed. Regions with entropy values exceeding the mean + 2 standard deviations from healthy controls (entropy: 0.0896 &#xb1; 0.0270) were isolated to quantify hyperentropic foci (HEF), representing HRF.<br><br>MAIN OUTCOME MEASURES: The sum and area of HEF were calculated as total HEF and area aggregate to compare before and after the treatment.<br><br>RESULTS: The mean patient age was 77.4 &#xb1; 8.6 years, with an equal distribution of males and females (6 each). Total HEF was significantly associated with worse baseline visual acuity (coefficient: 0.0015297, P = 0.0004). Faricimab treatment significantly reduced both total HEF (P = 0.0049) and area aggregate (P = 0.0068). However, conventional OCT did not detect significant improvements in total reflectivity nor area aggregate.<br><br>CONCLUSIONS: Polarization-sensitive OCT is a valuable imaging modality for extracting and quantifying HRF in the neurosensory retina. Faricimab significantly reduces HEF in nAMD eyes, highlighting its potential therapeutic effect beyond conventional OCT-detected changes.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosures may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40500586,
year = {2025},
author = {Wada, I and Nakao, S and Shiose, S and Kaizu, Y and Yamaguchi, M and Ishikawa, K and Kiyohara, K and Ishibashi, T and Sonoda, KH},
title = {En-face quantitative evaluation using ultra-high-resolution OCT of hyperreflective foci in neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {5},
pages = {738-744},
pmid = {40500586},
issn = {1613-2246},
support = {20K09829//JSPS KAKENHI/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Follow-Up Studies ; Fundus Oculi ; Ranibizumab/administration &amp; dosage ; *Macula Lutea/pathology ; Bevacizumab/administration &amp; dosage ; },
abstract = {PURPOSE: This study quantifies hyperreflective foci (HRFs) in neovascular age-related macular degeneration (nAMD) before and after anti-VEGF therapy in the initial loading phase using en-face ultra-high-resolution spectral domain OCT (UHR-SD-OCT), investigating their correlation with clinical findings.<br><br>STUDY DESIGN: Retrospective observational study METHODS: This retrospective study included 30 eyes from 30 patients with treatment-na&#xef;ve nAMD. The patients received monthly intravitreal injections of anti-VEGF therapy for three months as the initial loading phase. At each visit, comprehensive ophthalmic examinations were conducted. HRFs were quantified using our custom-developed&#xa0;software from an en-face UHR-SD-OCT. The number of HRFs was compared before and after the loading phase and investigated the relationship with best-corrected visual acuity (BCVA), greatest linear dimension (GLD), macular neovascularization (MNV) size and incidence of macular atrophy (MA).<br><br>RESULTS: This evaluation system showed a significant reduction in the number of HRFs after anti-VEGF therapy compared to before the loading phase (p < 0.0001). The number of pre-treatment HRFs significantly correlated with pre-treatment BCVA, GLD, and MNV size. The number of post-treatment HRFs significantly correlated with pre-treatment GLD and pre-treatment MNV size. Additionally, patients who developed MA two years after treatment initiation exhibited significantly higher counts of pre-treatment HRFs compared to those without the MA development (465.7 &#xb1; 187.0 vs. 212.9 &#xb1; 93.8, p < 0.05).<br><br>CONCLUSIONS: Quantification of HRF using en-face UHR-SD-OCT may be a useful clinical biomarker during anti-VEGF therapy in nAMD.},
}
@article {pmid40500585,
year = {2025},
author = {Ota, H and Takeuchi, J and Nonogaki, R and Tamura, K and Kaneko, H and Nishiguchi, KM},
title = {Efficacy of switching from existing anti-vascular endothelial growth factor drugs to ranibizumab biosimilar in neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {6},
pages = {886-893},
pmid = {40500585},
issn = {1613-2246},
support = {7122Jr-09c//Senju/ ; },
mesh = {Humans ; *Ranibizumab/administration &amp; dosage ; Prospective Studies ; Female ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Wet Macular Degeneration/drug therapy/diagnosis/metabolism ; *Drug Substitution ; *Biosimilar Pharmaceuticals/administration &amp; dosage ; Treatment Outcome ; Aqueous Humor/metabolism ; Tomography, Optical Coherence ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography ; Fundus Oculi ; },
abstract = {PURPOSE: This study evaluated the clinical outcomes and aqueous humor cytokine levels in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept to ranibizumab biosimilar (BS).<br><br>STUDY DESIGN: Prospective observational study.<br><br>METHODS: Thirty-eight eyes of 38 patients with nAMD who received aflibercept under a treat-and-extend (TAE) regimen were prospectively switched to ranibizumab BS. Eight eyes with cataracts undergoing surgery served as controls for aqueous humor cytokine analysis. Best-corrected visual acuity (BCVA) and anatomical outcomes were assessed over one year. The aqueous humor levels of vascular endothelial growth factor (VEGF)-A, angiopoietin-2 (Ang-2), and placental growth factor (PlGF) were measured before and after switching in eyes with nAMD and at surgery in controls.<br><br>RESULTS: Disease activity remained controlled in 94.3% of patients with nAMD for over one year. No significant changes were observed in the BCVA (P=0.65) after one year. Ang-2 levels remained unchanged (P=0.66) and were not significantly different between eyes with nAMD and controls both before (P=0.64) and after switching (P=0.30). PlGF levels also remained stable (P=0.12) but were significantly higher in eyes with nAMD than in controls both before (P<0.01) and after switching (P=0.03). VEGF-A levels significantly increased after switching (P<0.01) but remained lower than in the controls both before (P<0.01) and after switching (P=0.02).<br><br>CONCLUSION: Switching from aflibercept to ranibizumab BS effectively maintained disease stability and cytokine balance in eyes with nAMD. These findings support ranibizumab BS as a viable and cost-effective alternative for long-term treatment.},
}
@article {pmid40499938,
year = {2025},
author = {Faranoush, M and Khesali, F and Faranoush, P and Foroughi-Gilvaee, MR and Shams, P and Sadighnia, N and Ahmadi, SAY and Fallah Azad, D and Nekouian, R},
title = {Insights into retinoblastoma pathogenesis: unraveling RB1, N-MYC and miRNA profiles.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40499938},
issn = {2397-3269},
mesh = {Humans ; *Retinoblastoma/genetics/diagnosis/metabolism ; Male ; *MicroRNAs/genetics/biosynthesis ; Female ; Child, Preschool ; *Retinal Neoplasms/genetics/metabolism/diagnosis ; Child ; *Retinoblastoma Binding Proteins/genetics/biosynthesis ; *Ubiquitin-Protein Ligases/genetics/biosynthesis ; *Gene Expression Regulation, Neoplastic ; *N-Myc Proto-Oncogene Protein/genetics/biosynthesis ; Real-Time Polymerase Chain Reaction ; Biomarkers, Tumor/genetics ; },
abstract = {OBJECTIVE: Retinoblastoma is the most common paediatric intraocular malignancy, originating in neural retina germ cells. Early diagnosis is crucial for survival and eye preservation. This study analyses gene expression and specific microRNAs (miRNAs) in patients with retinoblastoma to enhance early diagnosis, prognosis and treatment strategies.<br><br>METHODS: This study examined gene and miRNA expression in 18 patients with retinoblastoma and 10 healthy individuals. Peripheral blood samples were collected from all participants, and patient demographics were recorded. The analysis was performed using real-time PCR targeting the RB1 and N-MYC genes, along with the miRNAs miR-125-5p, miR-221-3p and miR-519-3p.<br><br>RESULTS: The patient group consisted of 18 participants (9 males, 9 females), aged between 2 and 6 years (mean&#xb1;SD: 4.8&#xb1;1.33 years), with a mean diagnosis age of 3.01&#xb1;1.37 years. All participants were followed for 3 years, with no fatalities. The control group comprised 10 participants (4 males, 6 females), aged 2-8 years (mean&#xb1;SD: 5.01&#xb1;1.77 years). 11 patients underwent enucleation due to tumour progression: 3 right eyes and 8 left eyes. Gene expression analysis showed significant downregulation of miR-125-5p, miR-519-3p and NMYC in the retinoblastoma group. RB1 downregulation and miR-221-3p upregulation were noted in most patients, but without significant associations.<br><br>CONCLUSION: miRNAs, along with RB1 and N-MYC genes, may serve as predictive and prognostic biomarkers in retinoblastoma. While previous studies have highlighted the impact of certain miRNAs on survival and clinical outcomes, our study is limited by a small sample size and lack of strong statistical correlations. Large-scale studies are needed to validate these preliminary findings and clarify their clinical significance. Understanding the role of miRNAs in cancer biology could improve retinoblastoma mechanism insights and patient care.},
}
@article {pmid40499495,
year = {2025},
author = {Qin, S and Zhu, Y and Liu, Y and Xie, H and Zhang, J and Zhang, C and Xu, G},
title = {Nintedanib inhibits neovascularization and subretinal fibrosis in a laser-induced choroidal neovascularization mouse model.},
journal = {Biochemical and biophysical research communications},
volume = {775},
number = {},
pages = {152169},
doi = {10.1016/j.bbrc.2025.152169},
pmid = {40499495},
issn = {1090-2104},
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/pathology/etiology/metabolism ; Fibrosis/drug therapy ; *Indoles/administration &amp; dosage/pharmacology/therapeutic use ; Disease Models, Animal ; Mice ; Epithelial-Mesenchymal Transition/drug effects ; Mice, Inbred C57BL ; Cell Line ; Humans ; Lasers/adverse effects ; *Retina/pathology/drug effects ; Intravitreal Injections ; Cell Movement/drug effects ; Male ; Retinal Pigment Epithelium/drug effects/pathology ; },
abstract = {BACKGROUND: Subretinal fibrosis is a pivotal pathological factor contributing to vision loss in the elderly with neovascular age-related macular degeneration (nAMD), which is lack of effective treatment currently. The aim of this study was to assess the effects of nintedanib on subretinal fibrosis in a laser-induced choroidal neovascularization (CNV) mouse model and elucidate the molecular mechanisms of its action.<br><br>METHODS: The CNV mouse model was established by laser photocoagulation, and nintedanib was administered intravitreally 1 day after laser induction to verify the therapeutic efficacy of nintedanib on mice. TGF-&#x3b2;1 was employed to induce epithelial-mesenchymal transition (EMT) in ARPE-19&#xa0;cells. Subsequently, immunofluorescence, transwell migration, scratch assay and Western blot were employed to assess the effect of nintedanib on subretinal fibrosis, EMT and EMT-associated cell function.<br><br>RESULTS: The neovascular and fibrotic lesions exhibited a significant reduction in laser-induced CNV mice on days 7 and 14 after intravitreal injection of various concentrations of nintedanib. Compared to normal control mice, the expression of fibrosis markers (collagen-1, &#x3b1;-SMA and fibronectin) was significantly upregulated in the RPE-choroid-sclera complexes of CNV mice, which was effectively attenuated by nintedanib. Furthermore, following nintedanib treatment, the TGF-&#x3b2;1-induced EMT of the ARPE-19&#xa0;cells was significantly inhibited, as evidenced by a reduction in the levels of collagen-1, &#x3b1;-SMA, fibronectin, Vimentin and N-cadherin, along with a diminished capacity for cell migration. Mechanistically, nintedanib effectively blocked the activation of Smad 2/3, ERK 1/2, p38 and Akt signaling pathways in ARPE-19&#xa0;cells induced by TGF-&#x3b2;1.<br><br>CONCLUSION: The inhibition of subretinal fibrosis by nintedanib might be attributed to its suppression of EMT via inactivation of the Smad 2/3, ERK 1/2, p38 and Akt signaling pathways, thereby providing a potential molecule for the treatment of subretinal fibrosis.},
}
@article {pmid40499265,
year = {2025},
author = {Zhang, T and Jin, K and Zeng, S and Yang, P and Zhu, M and Zhang, J and Chen, Y and Lee, S and Yam, M and Zeng, Y and Lu, X and Loo, L and Neely, GG and Chang, A and Zhou, F and Du, J and Fan, X and Zhu, L and Gillies, MC},
title = {Divergent redox responses of macular and peripheral Müller Glia: Implications for retinal vulnerability.},
journal = {Redox biology},
volume = {85},
number = {},
pages = {103691},
pmid = {40499265},
issn = {2213-2317},
mesh = {*Ependymoglial Cells/metabolism/pathology ; Oxidation-Reduction ; Humans ; Oxidative Stress ; *Macula Lutea/metabolism/pathology ; *Retina/metabolism/pathology ; Animals ; Gene Expression Regulation ; Macular Degeneration/metabolism/genetics/pathology ; },
abstract = {The macula is preferentially affected in some common retinal diseases (such as age-related macular degeneration, diabetic retinopathy and macular telangiectasia type 2), whereas most inherited retinal degenerations (e.g., retinitis pigmentosa) tend to initially affect the peripheral retina. This pattern suggests the macula may have intrinsic vulnerabilities in its oxidative stress defences, compared to the periphery. Profiling of single-cell level transcriptional changes found that the peripheral retina exhibited greater transcriptional alterations than the macula in response to stress. One pronounced change was in a subgroup of Müller glia (MG) that was dominant in the peripheral retina. Genes more abundantly expressed in peripheral MG were mainly associated with redox regulation, oxidative stress responses and cellular detoxification and were more influenced by oxidative insults, such as light-induced stress. In contrast, genes highly expressed in macular MG were primarily involved in cellular homeostasis and neuroprotection, showing less responsiveness to oxidative challenges. Notably, Metallothionein 1 (MT1), A-Kinase Anchor Protein 12 (AKAP12) and MAF BZIP Transcription Factor F (MAFF) were significantly more expressed in peripheral MG than in macular MG, indicating a region-specific redox regulatory mechanism. Knockdown of these genes in primary MG led to decreased viability under oxidative stress, suggesting their role in antioxidant defence. Our findings indicate that macular MG prioritise retinal function over redox adaptation, which may contribute to their vulnerability to degenerative diseases associated with oxidative damage. These insights underscore the importance of region-specific redox homeostasis in retinal health and disease.},
}
@article {pmid40499235,
year = {2025},
author = {Tabilo, C and Squella, V and Illesca, P and Muñoz, Y and Farías, C and Valenzuela, R},
title = {Impact of n-3 polyunsaturate fatty acids supplementation on visual health throughout the life cycle: A systematic review.},
journal = {Prostaglandins, leukotrienes, and essential fatty acids},
volume = {206},
number = {},
pages = {102686},
doi = {10.1016/j.plefa.2025.102686},
pmid = {40499235},
issn = {1532-2823},
mesh = {Humans ; *Fatty Acids, Omega-3/administration &amp; dosage/pharmacology ; *Dietary Supplements ; Female ; *Vision, Ocular/drug effects ; Pregnancy ; Adult ; Male ; Child ; Randomized Controlled Trials as Topic ; Infant ; Child, Preschool ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; },
abstract = {INTRODUCTION: N-3 polyunsaturated fatty acids (n-3 PUFA) are important for mammals and have relevant functions in the body. These fatty acids play an important role in brain development, in the protection of the retina, and in the prevention of macular degeneration. Currently, clinical trials do not yet confirm a clear benefit of n-3 PUFA supplementation on vision throughout the life cycle. Therefore, the aim of this study is to systematically evaluate the available scientific evidence to determine the effects of n-3 PUFA supplementation on visual health throughout the life cycle.<br><br>MATERIAL AND METHODS: A search of scientific literature was performed, based on randomized, controlled clinical studies, published in PubMed, using keywords. We included people of both sexes throughout the life cycle that evaluated the impact of n-3 PUFA supplementation on visual health.<br><br>RESULTS: Of the 87 articles included in this review, there are important contradictions in the literature regarding the effects of supplementation in pregnant women, infants and older adults. While some studies highlight beneficial effects, an equal number of studies report no impact. In the case of preschoolers and schoolchildren, predominantly positive effects were identified, especially in children with Attention Deficit Hyperactivity Disorder (ADHD). For youth and adults, the impact of supplementation varied according to the health condition assessed, mostly supporting significant benefits in individuals with dry eye symptoms.<br><br>CONCLUSION: Evidence supports supplementation with n-3 PUFA, especially docosahexaenoic acid (DHA), to improve visual development in infants, schoolchildren, especially those with ADHD. Despite variability in visual outcomes, these findings suggest a crucial role of n-3 PUFA supplementation in visual health in the first steps of life, but in adults and older adults remain uncertain or null. Therefore, it is critical to investigate optimal dosing, duration of the intervention as the age of the participants in future research.},
}
@article {pmid40498743,
year = {2025},
author = {Sugisawa, T and Gomi, F and Harada, Y and Imaizumi, H and Aoki, S and Miki, A and Kishi, M and Yamauchi, T and Nagasato, D and Ozawa, Y and Haruta, M and Kato, N and Matsubara, H and Yasukawa, T and Kato, A and Terasaki, H and Hirano, T and Iesato, Y and Tsujinaka, H and Murakami, T and Mitamura, Y and Wakuta, M and Kimura, K and Shimura, M and , },
title = {Factors that contribute to loss to follow-up in the medium term after initiation of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration in Japanese patients.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0325963},
pmid = {40498743},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; Aged ; Retrospective Studies ; Japan/epidemiology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Case-Control Studies ; *Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; *Lost to Follow-Up ; Visual Acuity ; Follow-Up Studies ; Middle Aged ; East Asian People ; },
abstract = {PURPOSE: To identify time-specific factors associated with loss to follow-up (LTFU) in the early to medium term after initiating anti-vascular endothelial growth factor (VEGF) treatment in patients with neovascular age-related macular degeneration (nAMD) in Japan.<br><br>METHODS: The study had a retrospective multicenter case-control design and was performed across 16 specialist retinal facilities in Japan. Patients diagnosed with nAMD at their initial visit who initiated treatment between January 2017 and December 2020 were included. Patient characteristics were analyzed to identify factors associated with LTFU within 3 months (very early), 3 months to 1 year (early), and 1 year to 2 years (medium term) after starting treatment.<br><br>RESULTS: Data for 2389 patients with nAMD were analyzed. The very early, early, and medium-term LTFU rates were 6.8%, 13.8%, and 21.2%, respectively. Stepwise regression analysis identified factors that were significantly associated with LTFU at a very early stage to be greater central retinal thickness at baseline and a prior treatment history, those associated with early LTFU to be worse baseline best-corrected visual acuity (BCVA), anti-VEGF treatment combined with photodynamic therapy, and a follow-up period that overlapped with the COVID-19 pandemic, and that associated with medium-term LTFU to be worse BCVA at 3 months. LTFU in any period within 3 months to 2 years was more likely in patients aged >80 years, and LTFU very early within 3 months was more likely in those aged <60 years. A poor baseline BCVA (logMAR) of >1 was a risk factor for LTFU within 3 months and 1 year, whereas LTFU was significantly less likely in patients with good baseline BCVA (<0.1).<br><br>CONCLUSION: The LTFU rate in patients with nAMD increased over time. Factors contributing to LTFU vary depending on the time since initiation of treatment.},
}
@article {pmid40498279,
year = {2025},
author = {Faia, LJ and Ackert, J and Rodriguez, R and Abdul Sultan, A and Garey, C and Teneralli, RE and Ong, R},
title = {Comorbid Depression and Anxiety Risk in Older Individuals with Geographic Atrophy: A US Claims Data Analysis.},
journal = {Advances in therapy},
volume = {42},
number = {8},
pages = {3826-3838},
pmid = {40498279},
issn = {1865-8652},
mesh = {Humans ; Female ; Aged ; Male ; Retrospective Studies ; United States/epidemiology ; Comorbidity ; *Anxiety/epidemiology ; Middle Aged ; *Depression/epidemiology ; *Geographic Atrophy/psychology/epidemiology ; Aged, 80 and over ; Databases, Factual ; },
abstract = {INTRODUCTION: Geographic atrophy (GA), an advanced stage of nonexudative age-related macular degeneration (AMD), is associated with progressive central vision loss and blindness. While the association between GA and impaired vision-related quality of life has been established, understanding of the co-occurrence of anxiety and depression in individuals with GA is limited.<br><br>METHODS: We conducted a retrospective, noninterventional, cohort study analyzing data from three large US databases (Optum's de-identified Clinformatics[&#xae;] Data Mart Database [Clinformatics[&#xae;]], Merative&#x2122; MarketScan[&#xae;] Commercial and Medicare Databases [MarketScan], and IQVIA US PharMetrics[&#xae;] [PharMetrics]), employing a common data model. Patients aged&#x2009;&#x2265;&#x2009;50&#xa0;years with a diagnosis of GA were included and were matched to patients without GA in a 1:2 ratio using propensity score matching to create a non-GA/AMD control population. Outcomes included time from GA diagnosis to first interaction with a health care provider for depression or anxiety and health care resource utilization (HCRU). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated between GA and control cohorts with stratification by eye and subfoveal involvement.<br><br>RESULTS: The Clinformatics[&#xae;], MarketScan, and PharMetrics datasets included 44,595, 9468, and 27,427 patients with GA, respectively. Across databases, mean (SD) age ranged from 75.7 (8.3) to 80.5 (7.2) years, and 61% to 64% were female. Comorbid depression and anxiety risk were higher in patients with GA versus controls across datasets (depression RR [95%&#xa0;CI] 1.24 [1.13-1.35] to 1.36 [1.31-1.41]; anxiety RR [95%&#xa0;CI] 1.17 [1.06-1.30] to 1.33 [1.27-1.39]), with the greatest risk seen in those with bilateral GA with subfoveal involvement. HCRU was also significantly higher in patients with GA versus controls.<br><br>CONCLUSION: This study found a higher risk for comorbid depression or anxiety in patients with GA versus propensity score-matched controls. Risk was greatest among those with bilateral GA with subfoveal involvement. These findings highlight the important mental health burden experienced by patients with GA.},
}
@article {pmid40497378,
year = {2025},
author = {Anisetti, B and Stewart, MW and Markovic, D and Eggenberger, ER and Ertekin-Taner, N and Meschia, JF and Lin, MP},
title = {Age-related macular degeneration and risk of stroke and all-cause mortality.},
journal = {Neurologia i neurochirurgia polska},
volume = {59},
number = {4},
pages = {413-419},
doi = {10.5603/pjnns.98951},
pmid = {40497378},
issn = {0028-3843},
mesh = {Humans ; Female ; Male ; *Macular Degeneration/mortality/epidemiology/complications ; Middle Aged ; Aged ; *Stroke/mortality/epidemiology ; Risk Factors ; United States/epidemiology ; Adult ; Nutrition Surveys ; Aged, 80 and over ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the most common degenerative disorder of the retina and choroid. Retinal vascular diseases have been associated with adverse cardiovascular outcomes, but an association between AMD and stroke has not been well established. We aimed to test the relationship between AMD, stroke, and age-adjusted mortality.<br><br>MATERIAL AND METHODS: Data was obtained from the US National Health and Nutrition Examination Surveys 2005 to 2008, with linked mortality through to 2015. Participants aged 40 or older with gradable AMD on fundus photographs were included. AMD was classified as either early or late. Independent relationships between AMD and stroke were assessed using multivariable logistic regression models. Risk of all-cause mortality was assessed using Cox regression models, before and after adjusting for covariates.<br><br>RESULTS: Of the 5,481 participants included, 49.8% were women, 56.5% white, 20.3% black, and 15.5% Hispanic. 425 (7.8%) had AMD. After adjusting for vascular risk factors, we found that AMD was associated with an increased risk of stroke (aOR 1.87, 95% CI 1.25-2.79, p = 0.002). There was a relationship between AMD and stroke depending on whether participants had early AMD (aOR 1.66, 95% CI 1.09-2.51) or late AMD (aOR 3.32, 95% CI 1.36-8.12). All-cause mortality was higher in those with AMD (HR 1.35, 95% CI 1.06-1.72) and late AMD (HR 2.18, 95% CI 1.33-3.58).<br><br>CONCLUSIONS: Age-related macular degeneration is associated with stroke and all-cause mortality, independent of age and vascular risk factors. Our findings suggest potential non-vascular mechanisms related to the aetiology of AMD may increase the risk of stroke.},
}
@article {pmid40496348,
year = {2025},
author = {Jeong, HC and Cho, CS and Kim, JH and Chang, I and Kim, JH},
title = {Evaluating the Therapeutic Potential of Superoxide Dismutase in a Rat Model of Wet Age-Related Macular Degeneration.},
journal = {FASEB bioAdvances},
volume = {7},
number = {6},
pages = {e70015},
pmid = {40496348},
issn = {2573-9832},
abstract = {Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly, with limited oral treatment options for the wet form characterized by choroidal neovascularization (CNV). This study evaluated GF103, a mutant superoxide dismutase (SOD) from Bacillus amyloliquefaciens, for its potential as an oral therapy in a laser-induced CNV rat model. GF103 was orally administered at varying doses, and outcomes included CNV area, retinal leakage, and VEGF/HIF-1α expression. GF103 was well tolerated and significantly reduced CNV area and retinal VEGF expression at higher doses (≥ 25 mg/kg for retinal VEGF expression; ≥ 50 mg/kg for CNV area). While reductions in fluorescein leakage and HIF-1α levels were not statistically significant, trends suggested modulation of oxidative and hypoxia-related pathways. These results support the potential of GF103 as a safe oral adjunct to existing therapies for wet AMD, meriting further investigation.},
}
@article {pmid40496216,
year = {2025},
author = {Sideri, O and Correa, V and Ziakas, N and Tsinopoulos, I and Miller, JW and Vavvas, DG},
title = {Systematic Review of Proteomics in Age-Related Macular Degeneration and Pathway Analysis of Significant Protein Changes.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100793},
pmid = {40496216},
issn = {2666-9145},
support = {R01 EY030088/EY/NEI NIH HHS/United States ; },
abstract = {TOPIC: Proteomics in age-related macular degeneration (AMD) research.<br><br>CLINICAL RELEVANCE: AMD is the leading cause of blindness in industrialized countries, with a poorly understood pathogenesis. Proteomics can identify significantly altered proteins in AMD patients, aiding in understanding the disease's pathophysiology and potentially improving diagnosis or treatment strategies.<br><br>METHODS: A systematic review of proteomic studies in AMD was conducted. Proteins significantly altered in dry and wet AMD and those tested as biomarkers were presented according to sample type (aqueous humor, plasma, urine, vitreous, retinal pigment epithelium/choroid, and tear film) and type of assay (mass spectrometry or aptamers) used in the individual studies. Proteins that exhibited at least a 2&#xd7; fold change (FC) were further analyzed through functional enrichment analysis and protein-protein interaction networks (STRING database).<br><br>RESULTS: Twenty-two studies (case-control and cohorts) with a total of 6932 participants were included. The included studies showed significant heterogeneity, and most of them lacked sufficient power. Results suggested that various proteins and pathways are implicated in AMD, and there were differences when comparing results from the individual studies and unbiased results. Although many proteins differed significantly between AMD and control groups, most exhibited less than a 2-FC. Functional analysis of proteins with &#x2265;|2|-FCs (identified by unbiased proteomics in multiple biofluids) highlighted lipid metabolism and protease regulation pathways as central to both dry and wet AMD. Complement and coagulation cascades, chaperones, and glycolysis pathways were significant in wet AMD, whereas matrix remodeling pathways were enriched mostly in dry AMD.<br><br>CONCLUSION: Combining proteomics from various studies could reveal new protein-protein interaction networks and associated functional pathways that may suggest novel potential therapeutic targets for AMD. However, there is a scarcity of data available for early AMD from ocular biofluids, and it should be the aim of future proteomics studies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40494650,
year = {2025},
author = {Chen, PJ and Lee, JL and Wan, L and Lin, HJ and Chen, WL and Chen, SN and Lin, CJ and Lin, JM and Lai, CT and Hsia, NY and Huang, YT and Tsai, YY and Lin, HJ and Hsieh, YW and Cheng, YD and Tsai, FJ and Chou, CC and Tien, PT},
title = {Impact of long-term statin therapy on age-related macular degeneration: A nationwide population-based study.},
journal = {British journal of clinical pharmacology},
volume = {91},
number = {10},
pages = {2946-2956},
doi = {10.1002/bcp.70128},
pmid = {40494650},
issn = {1365-2125},
support = {DMR-112-102; DMR-113-121; DMR-113-205; DMR-113-084//China Medical University Hospital/ ; DMR-112-102//China Medical University Hospital/ ; DMR-113-121//China Medical University Hospital/ ; DMR-113-205//China Medical University Hospital/ ; DMR-113-084//China Medical University Hospital/ ; MOHW113-TDU-B-212-114009//Taiwan Ministry of Health and Welfare Clinical Trial Center/ ; },
mesh = {Humans ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration &amp; dosage/therapeutic use ; Male ; Female ; Taiwan/epidemiology ; Aged ; *Macular Degeneration/epidemiology/prevention &amp; control ; Incidence ; Middle Aged ; Databases, Factual ; Aged, 80 and over ; Time Factors ; Risk Factors ; Kaplan-Meier Estimate ; Proportional Hazards Models ; },
abstract = {AIMS: Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide among older adults. Although some studies propose that statins could reduce AMD risk and progression, others report conflicting findings. This study aimed to evaluate the impact of statin use on the incidence of AMD.<br><br>METHODS: This study used Taiwan's National Health Insurance Research Database (2000-2021) with the LGTD2000 cohort. Participants were categorized into statin users (&#x2265;6&#x2009;months, 2001-2020) and nonusers. AMD incidence was analysed using Cox regression and Kaplan-Meier methods, with propensity score matching applied to report adjusted hazard ratios (AHRs) and confidence intervals (CIs).<br><br>RESULTS: After adjusting for confounding factors, statin use for over 2&#xa0;years was associated with a significantly lower risk of AMD compared to nonstatin users (AHR&#x2009;=&#xa0;0.79, 95% CI: 0.69-0.91). Subgroup analyses demonstrated that long-term statin use (&#x2265;730&#x2009;days) showed protective associations across most sex and age groups. Specifically, risk reduction was observed for both non-neovascular AMD (AHR&#x2009;=&#xa0;0.84, 95% CI: 0.70-1.02) and neovascular AMD (AHR&#x2009;=&#xa0;0.72, 95% CI: 0.59-0.88). Furthermore, dose-response analysis revealed that higher cumulative statin exposure was associated with a decreased AMD risk, while lower cumulative exposure was associated with an increased risk.<br><br>CONCLUSION: This study indicated that prolonged statin use exceeding 2 years was associated with a significantly decreased risk of developing both non-neovascular and neovascular AMD.},
}
@article {pmid40493982,
year = {2025},
author = {Yang, B and Yang, K and Xi, R and Li, S and Chen, J and Wu, Y},
title = {Long-term senolytic therapy with Dasatinib and Quercetin alleviates lipofuscin-dependent retinal degeneration in mice.},
journal = {Redox biology},
volume = {85},
number = {},
pages = {103716},
pmid = {40493982},
issn = {2213-2317},
mesh = {Animals ; Mice ; *Lipofuscin/metabolism ; *Dasatinib/pharmacology/therapeutic use/administration &amp; dosage ; *Quercetin/pharmacology/therapeutic use/administration &amp; dosage ; Disease Models, Animal ; *Retinal Degeneration/drug therapy/metabolism/pathology/etiology ; Mice, Knockout ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Oxidative Stress/drug effects ; *Senotherapeutics/pharmacology ; Macular Degeneration/drug therapy/metabolism/pathology ; ATP-Binding Cassette Transporters/genetics ; Alcohol Oxidoreductases/genetics ; },
abstract = {Dry age-related macular degeneration (AMD) is one of the common blinding eye diseases, with pathological hallmarks of lipofuscin accumulation, neuroretina atrophy and retinal pigment epithelium (RPE) degeneration. Currently, there are no effective interventions for dry AMD. Although there is already evidence suggesting a link between cellular senescence and age-related diseases, it is still unclear whether long-term senolytic therapy with Dasatinib and Quercetin (D + Q) can slow the progression of dry AMD and ultimately prevent retinal structural damage and function loss. Mice lacking the Abca4 and Rdh8 genes (Abca4[-/-]Rdh8[-/-] mice) are a preclinical model of dry AMD. In this study, we performed a 4-month senolytic therapy with D + Q on 4-month-old Abca4[-/-]Rdh8[-/-] mice. Abca4[-/-]Rdh8[-/-] mice at the age of 8 months showed obvious retinal degeneration, along with RPE senescence, lysosomal alkalinization, lipofuscin accumulation and oxidative stress. Importantly, the long-term D + Q regimen significantly alleviated the degeneration of retinal structures and function in 8-month-old Abca4[-/-]Rdh8[-/-] mice, and it effectively repressed cellular senescence, lysosomal alkalinization, lipofuscin accumulation and oxidative stress in the RPE. This study is the first to demonstrate the effect of long-term intervention with senolytics D + Q on dry AMD. Overall, these findings highlight the potential of long-term senolytic treatment as an intervention for dry AMD.},
}
@article {pmid40493193,
year = {2025},
author = {Wang, Y and Zhang, YC and Ding, ZQ and Xu, SY and Zhang, YR and Zhu, HJ and Huang, C and Wang, JN and Zhu, M and Ji, JD and Yan, B and Liu, QH and Chen, X},
title = {Feedback regulation between histone lactylation and ALKBH3-mediated glycolysis regulates age-related macular degeneration pathology.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {24},
pages = {e2416046122},
pmid = {40493193},
issn = {1091-6490},
support = {82471105//MOST | National Natural Science Foundation of China (NSFC)/ ; 82070974//MOST | National Natural Science Foundation of China (NSFC)/ ; 82471096//MOST | National Natural Science Foundation of China (NSFC)/ ; 82271100//MOST | National Natural Science Foundation of China (NSFC)/ ; BK20231371//JST | Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; NA//"333 Project" of Jiangsu Province ("333" Project of Jiangsu Province)/ ; BE2022805//Social Development Program of Jiangsu Province/ ; CZ0121002010037//Jiangsu Province Hospital High-level Talent Cultivation Program (Phase I)/ ; NM202409//The Joint Open Research Fund of Suzhou Institute of Nanotechnology and Nano-bionics &amp; Jiangsu Province Hospital and the Medical Engineering Translational Fund of Jiangsu Province Hospital/ ; },
mesh = {*Macular Degeneration/metabolism/pathology/genetics ; Animals ; Mice ; Humans ; Retinal Pigment Epithelium/metabolism/pathology ; *Glycolysis ; *Histones/metabolism ; Mice, Knockout ; *AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase/metabolism/genetics ; Vascular Endothelial Growth Factor A/metabolism/genetics ; Feedback, Physiological ; Choroidal Neovascularization/metabolism/pathology/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. It is characterized by degeneration of the retinal pigment epithelium (RPE), which can develop into choroidal neovascularization (CNV) to cause severe and rapid vision loss. Preventing this progression might help save vision, but the exact mechanisms remain unclear. In this study, using clinical AMD samples and the gene knockout mice, we reported that the m[1]A eraser ALKBH3 reshaped retinal metabolism to promote this progression. In RPE, the dm[1]ACRISPR system demonstrated that ALKBH3 demethylated the rate-limiting glycolytic enzyme HK2 to activate glycolysis, resulting in excess lactate production. This lactate promoted histone lactylation at H3K18, which in turn bound to ALKBH3 to amplify its transcription, establishing a positive feedback loop. The ALKBH3 inhibitor HUHS015 disrupted this loop, effectively mitigating RPE degeneration. Furthermore, ALKBH3 directly targeted the proangiogenic factor VEGFA to modulate the metabolic cross-talk between RPE and choroidal capillaries, thus promoting CNV. HUHS015 inhibited CNV synergistically with the anti-VEGF drug Aflibercept. Overall, our study provides critical insights into the molecular mechanisms and metabolic events that facilitates the progression from RPE degeneration to CNV in AMD, laying the groundwork for new treatments of age-related retinal disorders.},
}
@article {pmid40492987,
year = {2025},
author = {Sasaki, M and Cheong, KX and Chong, CCY and Yu, M and Hanyuda, A and Yuki, K and Negishi, K and Hashimoto, S and Fujiwara, K and Sonoda, K and Wang, YX and Gao, F and Amornpetchsathaporn, A and Chainakul, M and Srinivasan, R and Khan, R and Raman, R and Ruamviboonsuk, P and Kim, SH and Song, SJ and Emamian, MH and Hashemi, H and Fotouhi, A and Liu, J and Li, X and Jonas, JB and Cheung, CMG and Wong, TY and Cheng, CY and Tham, YC and Yanagi, Y and Tan, ACS},
title = {Relationship of Choroidal Thickness With Age-Related Macular Degeneration in Asians: An Asian Eye Epidemiology Consortium Meta-Analysis.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {36},
pmid = {40492987},
issn = {1552-5783},
mesh = {Humans ; *Choroid/pathology ; Tomography, Optical Coherence/methods ; Male ; *Asian People/ethnology ; Female ; Middle Aged ; *Macular Degeneration/epidemiology/ethnology/diagnosis/pathology ; Aged ; Asia/epidemiology ; Singapore/epidemiology ; },
abstract = {PURPOSE: To compare the choroidal thickness (CT) of participants with various stages of age-related macular degeneration vs. normal controls through a meta-analysis of studies conducted within the Asian Eye Epidemiology Consortium.<br><br>METHODS: Eight population-based studies from China, Iran, Japan, and Singapore were included. Axial length and spherical equivalent measurements and imaging with color fundus photography and spectral-domain optical coherence tomography were performed. Random-effects meta-analysis was performed to examine the association between AMD and its stages (early AMD, intermediate AMD [iAMD], neovascular AMD [nAMD], and geographic atrophy [GA]) with CT, while adjusting for age, sex, current smoking status, and axial length/spherical equivalent.<br><br>RESULTS: Of 17,916 participants, 13,116 participants (mean age, 62.15 &#xb1; 9.66&#xa0;years) were included into the study. The mean unadjusted CT was 245.01 &#xb1; 84.04&#xa0;&#xb5;m (mean CT, 255.4&#xa0;&#xb5;m [no AMD], 263.59&#xa0;&#xb5;m [early AMD], 270.64&#xa0;&#xb5;m [iAMD], 273.32&#xa0;&#xb5;m [nAMD], and 156.50&#xa0;&#xb5;m [GA]). The presence of AMD was associated with a thicker choroid (&#x3b2; = 11.51; 95% confidence interval [CI], 4.10-18.92). AMD severity was also positively associated with CT. Early AMD (&#x3b2; = 8.75; 95% CI, 0.03-17.47), iAMD (&#x3b2; = 19.68; 95% CI, 13.20-26.16), and nAMD (&#x3b2; = 34.15; 95% CI, 6.84-61.46) were each positively associated with a thicker CT after adjusting for age, sex, smoking, and spherical equivalent. GA was not significantly associated with CT.<br><br>CONCLUSIONS: In a large Asian cohort, AMD is associated with a thicker choroid in early AMD, iAMD, and nAMD, but not in GA. Studying the CT will help to better characterize Asian AMD phenotypes, which may show differences compared with AMD phenotypes in Western populations.},
}
@article {pmid40492668,
year = {2025},
author = {Kopecny, LR and Agar, A and Wong, SW},
title = {Vision &amp; the Ageing Surgeon: A Review.},
journal = {ANZ journal of surgery},
volume = {95},
number = {7-8},
pages = {1312-1319},
doi = {10.1111/ans.70213},
pmid = {40492668},
issn = {1445-2197},
mesh = {Humans ; *Aging/physiology ; *Surgeons ; *Vision, Ocular/physiology ; Aged ; },
abstract = {Populations in the developed world are ageing and their surgeons are no exception. Accurate vision is essential for the surgeon to operate effectively, yet optimal vision has an expiry date in advancing age. This review examines the effects of ageing on the eye with particular focus on the visual changes of significance to senior surgeons who currently account for 20%-25% of the surgeon workforce. The major age-related diseases of the eye, which include cataracts, glaucoma, age-related macular degeneration and diabetic retinopathy, are surmised; together with physiologic ocular changes that accompany normal ageing, including loss of accommodation (presbyopia), reduced pupil size (senile miosis), reduced contrast sensitivity, and impaired binocular vision, amongst others. The aforementioned conditions may impair operative visualisation in the elderly surgeon and potentially impact surgical performance. Strategies and available technologies that support operative visualisation-particularly magnification aids, illumination systems and fluorescent dyes in surgery-are appraised with consideration to the senior surgeon who may be affected by the aforementioned visual changes associated with ageing. To inform minimum standards of visual function for safe surgical practice, future prospective studies are needed which report on individual surgeon-related measures of visual function together with postoperative outcomes. This vein of future research will allow for an evidence-based evaluation of proposed safety measures for which the data are currently lacking, thereby providing clarity regarding whether requisite age-based visual assessments improve surgical outcomes, and if so, at what age and frequency should such evaluations take place.},
}
@article {pmid40492092,
year = {2025},
author = {Siraz, S and Kamanda, H and Gholami, S and Nabil, AS and Yee Ong, SS and Alam, MN},
title = {Multi-class classification of central and non-central geographic atrophy using Optical Coherence Tomography.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.27.25328446},
pmid = {40492092},
support = {R21 EY035271/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To develop and validate deep learning (DL)-based models for classifying geographic atrophy (GA) subtypes using Optical Coherence Tomography (OCT) scans across four clinical classification tasks.<br><br>DESIGN: Retrospective comparative study evaluating three DL architectures on OCT data with two experimental approaches.<br><br>SUBJECTS: 455 OCT volumes (258 Central GA [CGA], 74 Non-Central GA [NCGA], 123 no GA [NGA]) from 104 patients at Atrium Health Wake Forest Baptist. For GA versus age-related macular degeneration (AMD) classification, we supplemented our dataset with AMD cases from four public repositories.<br><br>METHODS: We implemented ResNet50, MobileNetV2, and Vision Transformer (ViT-B/16) architectures using two approaches: (1) utilizing all B-scans within each OCT volume and (2) selectively using B-scans containing foveal regions. Models were trained using transfer learning, standardized data augmentation, and patient-level data splitting (70:15:15 ratio) for training, validation, and testing.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC-ROC), F1 score, and accuracy for each classification task (CGA vs. NCGA, CGA vs. NCGA vs. NGA, GA vs. NGA, and GA vs. other forms of AMD).<br><br>RESULTS: ViT-B/16 consistently outperformed other architectures across all classification tasks. For CGA versus NCGA classification, ViT-B/16 achieved an AUC-ROC of 0.728&#xb1;0.083 and accuracy of 0.831&#xb1;0.006 using selective B-scans. In GA versus NGA classification, ViT-B/16 attained an AUC-ROC of 0.950&#xb1;0.002 and accuracy of 0.873&#xb1;0.012 with selective B-scans. All models demonstrated exceptional performance in distinguishing GA from other AMD forms (AUC-ROC>0.998). For multi-class classification, ViT-B/16 achieved an AUC-ROC of 0.873&#xb1;0.003 and accuracy of 0.751&#xb1;0.002 using selective B-scans.<br><br>CONCLUSIONS: Our DL approach successfully classifies GA subtypes with clinically relevant accuracy. ViT-B/16 demonstrates superior performance due to its ability to capture spatial relationships between atrophic regions and the foveal center. Focusing on B-scans containing foveal regions improved diagnostic accuracy while reducing computational requirements, better aligning with clinical practice workflows.},
}
@article {pmid40491639,
year = {2025},
author = {Yasuda, S and Tsujinaka, H and Nishiyama, T and Mizusawa, Y and Ueda, T},
title = {Intraocular Inflammation Following Faricimab Intravitreal Injection Treated With Sub-tenon Triamcinolone Acetonide Injection.},
journal = {Cureus},
volume = {17},
number = {5},
pages = {e83764},
pmid = {40491639},
issn = {2168-8184},
abstract = {We report the management of intraocular inflammation (IOI) following faricimab intravitreal injection. Severe IOI was observed in three eyes (one eye with age-related macular degeneration (AMD) and two eyes in the same patient with diabetic macular edema (DME)). These three eyes had fine keratic precipitates, inflammatory cells in the anterior chamber, and vitreous opacity, with decreased best-corrected visual acuity (BCVA) in all patients. Blood tests did not reveal any abnormalities, and anterior chamber multiplex polymerase chain reaction and bacterial cultures were negative. Sub-tenon triamcinolone acetonide (STTA) injections improved anterior inflammation, vitreous opacity, and BCVA, although posterior iris synechia caused by inflammation persisted in one patient. Faricimab injection can induce IOI. In this study, IOI was managed with a STTA injection during the early stage of uveitis. Severe inflammation can lead to complications such as posterior iris synechia.},
}
@article {pmid40491424,
year = {2025},
author = {Xie, X and Lian, S and Yang, W and He, S and He, J and Wang, Y and Zeng, Y and Lu, F and Jiang, J},
title = {Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS/STING pathway.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {5},
pages = {101145},
pmid = {40491424},
issn = {2214-0883},
abstract = {Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.},
}
@article {pmid40490296,
year = {2025},
author = {Merle, DA and Guymer, RH and Chia, MA and Chopra, R and Williamson, DJ and Struyven, RR and Jannaud, M and Hadoux, X and van Wijngaarden, P and Keane, PA and Wu, Z},
title = {Mapping the impact: AI-driven quantification of geographic atrophy on OCT scans and its association with visual sensitivity loss.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {10},
pages = {1187-1193},
doi = {10.1136/bjo-2024-326603},
pmid = {40490296},
issn = {1468-2079},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/physiopathology/diagnosis/etiology ; Male ; Aged ; Female ; Visual Field Tests ; *Visual Fields/physiology ; *Artificial Intelligence ; *Visual Acuity/physiology ; Aged, 80 and over ; Middle Aged ; Macular Degeneration/complications ; Fluorescein Angiography ; },
abstract = {BACKGROUND/AIMS: To examine the association between artificial intelligence (AI)-driven segmentation of geographic atrophy (GA) on optical coherence tomography (OCT) and visual sensitivity loss quantified by defect-mapping microperimetry, a testing strategy optimised to quantify the spatial extent of deep visual sensitivity losses.<br><br>METHODS: 50 individuals with GA secondary to age-related macular degeneration underwent defect-mapping microperimetry testing within the central 8&#xb0; radius region in one eye. GA on OCT was automatically segmented with an AI-based multiclass classification and segmentation model, and GA on fundus autofluorescence (FAF) images was manually annotated. Their extent in the topographically corresponding region sampled on microperimetry was derived, and structure-function relationships were examined based on Spearman correlation coefficients (&#x3c1;). The distance of each test location from the OCT-defined and FAF-defined GA margin was also derived and used in prediction models of non-response on defect-mapping microperimetry.<br><br>RESULTS: There was a strong correlation between the proportion of locations missed on defect-mapping microperimetry and the corresponding percentage of the central 8&#xb0; radius region with GA on OCT (&#x3c1;=0.85) and FAF (&#x3c1;=0.89). Prediction models for non-response at individual test locations using GA derived from OCT and FAF imaging had a sensitivity of 59% and 62% (p=0.310), respectively, at 95% specificity.<br><br>CONCLUSIONS: AI-driven, automated quantification of GA on OCT showed a strong correlation with the global extent of visual sensitivity loss, comparable with those based on manual annotations on FAF imaging. These findings affirm the expected functional relevance of OCT-derived GA measurements and their clinical utility for monitoring disease progression in those with GA.},
}
@article {pmid40489855,
year = {2025},
author = {Jezani, SN and Bastion, MC},
title = {Usage of brolucizumab as treatment for wet age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV): A narrative review.},
journal = {Medicine},
volume = {104},
number = {23},
pages = {e42666},
pmid = {40489855},
issn = {1536-5964},
mesh = {Humans ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; Intravitreal Injections ; *Choroidal Neovascularization/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Polypoidal Choroidal Vasculopathy ; },
abstract = {Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the gold standard treatment for neovascular age-related macular degeneration (nAMD) which is responsible for central vision loss. This results in loss of quality of life, comparably severe to having coronary artery disease or cancer. New anti-VEGF agents need to address issues of potency and durability as existing agents tend to lose their effect after 1 month thus, requiring multiple injections at close intervals. Brolucizumab is one of the latest anti-VEGF agents clinically proven to treat nAMD after on-label agents namely, ranibizumab and aflibercept. Several clinical trials were conducted on Brolucizumab to ensure its safety and efficiency before it is approved to be used as treatment. Brolucizumab maintains and improves retinal edema in nAMD leading to improved vision with longer intervals possible between injections. However, it also has a risk of intraocular inflammation. This review summarizes the evidence for brolucizumab in the treatment of nAMD.},
}
@article {pmid40488713,
year = {2025},
author = {Sreekumar, PG and Nam, MH and Hong, E and Kannan, R and Nagaraj, RH},
title = {RAGE Is Essential for Subretinal Fibrosis in Laser-Induced Choroidal Neovascularization: Therapeutic Implications.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {30},
pmid = {40488713},
issn = {1552-5783},
support = {R01 EY030141/EY/NEI NIH HHS/United States ; R01 EY033915/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Choroidal Neovascularization/metabolism/etiology/pathology ; Fibrosis/metabolism ; Mice ; *Receptor for Advanced Glycation End Products/antagonists &amp; inhibitors/physiology ; Male ; Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Epithelial-Mesenchymal Transition ; Tomography, Optical Coherence ; Mice, Knockout ; Laser Coagulation/adverse effects ; Cells, Cultured ; Signal Transduction ; Transforming Growth Factor beta2/pharmacology ; Benzamides ; },
abstract = {PURPOSE: Subretinal fibrosis, a complication of neovascular age-related macular degeneration (nAMD), involves the epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells as a contributing mechanism. The receptor for advanced glycation end products (RAGE) is a multiligand receptor implicated in fibrotic diseases, but its role in subretinal fibrosis has not been studied. This study investigated the role of RAGE in subretinal fibrosis.<br><br>METHODS: Subretinal fibrosis was induced in male RAGE-/- and wild-type (WT) mice via laser photocoagulation, and fibrosis lesion volume was assessed on day 35 using optical coherence tomography and immunostaining. In vitro, EMT was induced in primary human RPE cells with transforming growth factor-beta 2 (TGF-&#x3b2;2). The role of RAGE in EMT was studied in cells pretreated with RAGE antagonists (FPS-ZM1 or azeliragon), followed by cotreatment with TGF-&#x3b2;2 for 48&#xa0;hours. Signaling studies were conducted by pretreatment with FPS-ZM1 for 2&#xa0;hours, cotreatment with TGF-&#x3b2;2 for 60&#xa0;minutes, and subsequent immunoblot analysis.<br><br>RESULTS: In RAGE-/- mice, subretinal fibrosis after laser-induced choroidal neovascularization was significantly reduced, with a smaller fibrosis volume, less inflammation, decreased activation of pSmad2, and reduced deposition of fibrotic markers (&#x3b1;SMA, collagen I) compared to WT mice. In vitro treatment with TGF-&#x3b2;2 in human RPE cells increased mitochondrial reactive oxygen species and upregulated EMT markers (&#x3b1;SMA, collagen I, and fibronectin), which were inhibited by cotreatment with FPS-ZM1 or azeliragon. FPS-ZM1 blocked TGF-&#x3b2;2-induced Smad2-dependent signaling and EMT without affecting the extracellular signal-regulated kinase (ERK) pathway.<br><br>CONCLUSIONS: Our findings indicate that RAGE plays a role in RPE cell EMT in subretinal fibrosis and that RAGE antagonists attenuate this process, making RAGE a promising therapeutic target for subretinal fibrosis in nAMD.},
}
@article {pmid40488701,
year = {2025},
author = {Arora, S and Singh, SR and Vupparaboina, SC and Rosario, B and Ibrahim, MN and Selvam, A and Zarnegar, A and Harihar, S and Sant, V and Sahel, JA and Vupparaboina, KK and Chhablani, J},
title = {Three-Dimensional Choroidal Contour Mapping in Healthy and Diseased Eyes.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {6},
pages = {16},
pmid = {40488701},
issn = {2164-2591},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/diagnostic imaging/pathology ; Retrospective Studies ; Female ; Male ; Middle Aged ; *Tomography, Optical Coherence/methods ; *Imaging, Three-Dimensional/methods ; *Central Serous Chorioretinopathy/diagnostic imaging/pathology ; Aged ; *Macular Degeneration/diagnostic imaging ; Adult ; *Geographic Atrophy/diagnostic imaging ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: Quantitative evaluation of choroidal curvature including choroidal inner boundary (CIB) and choroidal outer boundary (COB) and report a comparison between healthy and diseased eyes.<br><br>METHODS: This retrospective study was conducted on 97 eyes of 97 patients. Eyes were divided into three groups: central serous chorioretinopathy (CSCR), dry age-related macular degeneration (AMD), and healthy eyes. Delineation of CIB and COB was performed using a hybrid method based on our previously validated deep learning and three-dimensional (3D) smoothing methods for choroidal layer segmentation. Quantitative analysis of the surfaces was based on best-fit spherical radius (R). R for overall surface, as well as for each region (central/nasal/temporal/superior/inferior region), was estimated. Statistical analysis was done using SPSS software.<br><br>RESULTS: There were 35 healthy eyes, 32 eyes with CSCR, and 30 eyes with dry AMD. At CIB and COB; RCSCR > Rhealthy > RAMD (P &#x2264; 0.001). The central region had the lowest R among all the regions within a group at CIB and COB (P&#xa0;<&#xa0;0.001) in healthy, CSCR, and AMD eyes. There was moderate positive correlation of R of CIB and COB with subfoveal choroidal thickness in healthy eyes and a negligible/weak correlation in CSCR and AMD eyes.<br><br>CONCLUSIONS: Contour of choroid at CIB and COB was the flattest in CSCR and steepest in AMD. Central region was the steepest among all sectors in both healthy and diseased eyes.<br><br>TRANSLATIONAL RELEVANCE: Quantitative study of surface at CIB and COB in diseases helps in understanding the pathophysiological changes and provides a clinical biomarker in disease monitoring and treatment as well.},
}
@article {pmid40488699,
year = {2025},
author = {Adeyoju, DAO and Josan, AS and Taylor, LJ and MacLaren, RE},
title = {An Analysis of Scotopic Microperimetry in Healthy Adults.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {6},
pages = {18},
pmid = {40488699},
issn = {2164-2591},
mesh = {Humans ; Male ; Female ; *Visual Field Tests/methods ; Reproducibility of Results ; Adult ; *Visual Fields/physiology ; Young Adult ; *Night Vision/physiology ; Dark Adaptation/physiology ; Healthy Volunteers ; Visual Acuity/physiology ; *Retina/physiology ; },
abstract = {PURPOSE: Scotopic microperimetry measures retinal sensitivity under very low light and may be useful in conditions characterized by nyctalopia, such as retinitis pigmentosa and age-related macular degeneration. The Scotopic Macular Integrity Assessment device enables two-color perimetry to isolate rod and cone responses. This study assesses the reliability, test-retest repeatability, and sensitivity in healthy participants aiming to establish normative values.<br><br>METHODS: Scotopic microperimetry was performed using cyan and red stimuli on a 37-point radial grid after dark adaptation on control participants with no history of eye disease and visual acuity of 0.1 logarithm of the minimum angle of resolution or better. Fixation stability, fixation losses, and identification of the rod-free zone were used as reliability metrics. A subset underwent repeat testing within 4 weeks.<br><br>RESULTS: Thirty-nine participants (19 male and 20 female), median age 24&#xa0;years (interquartile range, 9.5&#xa0;years) and 23 years (interquartile range, 9&#xa0;years) for the right and left eyes, respectively, completed testing. Overall 77 eyes underwent scotopic testing, with 82% meeting reliability criteria. Mean cyan and red sensitivities were 19.9 &#xb1; 1.1&#xa0;dB and 20.9 &#xb1; 1.2&#xa0;dB in right eyes, and 20.1 &#xb1; 1.4&#xa0;dB and 21.3 &#xb1; 1.4 dB in left eyes, respectively. Volumetric cyan and red sensitivities were 2868 &#xb1; 157&#xa0;dB.deg2 and 3077 &#xb1; 176&#xa0;dB.deg2 in the right eyes, respectively, and 2892 &#xb1; 205&#xa0;dB.deg2 and 3126 &#xb1; 207&#xa0;dB.deg2 in the left eyes, respectively. Mean sensitivity coefficients of repeatability (CoR) were &#xb1; 1.4 dB (cyan) and &#xb1; 2.1 dB (red) while pointwise coefficients of repeatability were &#xb1; 7.2 dB (95% confidence interval, 6.5-7.6&#xa0;dB) for cyan and &#xb1; 7.9 dB (95% confidence interval, 7.3-8.4&#xa0;dB) for red, with no significant differences between eyes or genders. Fixation stability assessed using the 95% bivariate contour ellipse area for cyan was 2.9 &#xb1; 5.9 deg2 and 2.3 &#xb1; 2.2 deg2 for the right and left eyes, respectively, and for red were 0.7 &#xb1; 0.6 deg2 and 0.9 &#xb1; 0.8 deg2 for the right and left eyes, respectively. Again, there were no significant differences between cyan and red tests (Friedman test, bivariate contour ellipse area 63%, P = 0.455; bivariate contour ellipse area 95%, P = 0.432).<br><br>CONCLUSIONS: Scotopic microperimetry using the Scotopic Macular Integrity Assessment device was feasible and well-tolerated. Repeatability metrics demonstrated limitations in fine spatial mapping of scotopic retinal sensitivity.<br><br>TRANSLATIONAL RELEVANCE: This study highlights potential areas for future improvements in scotopic microperimetry before its use as an outcome measure in clinical trials for retinal disease.},
}
@article {pmid40488118,
year = {2025},
author = {Alemu, DS and Munaw, MB and Bekele, MM and Asmare Kindie, C and Ayele, FA and Limenih, MA},
title = {Determinants of Healthcare Professionals' Knowledge on Age-Related Macular Degeneration Risk Factors in Ethiopia.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1771-1785},
pmid = {40488118},
issn = {1177-5467},
abstract = {PURPOSE: The aim of this study was to assess knowledge of healthcare professionals on risk factors of age-related macular degeneration and to identify factors that affect their level of knowledge.<br><br>PATIENTS AND METHODS: A cross-sectional study design was employed to collect data from 607&#xa0;healthcare professionals in Gondar City from August 1 to 30, 2024. Systematic random sampling was used to select study participant. Interviewer administered questionnaire was used to collect data. Bi-variable and multivariable logistic regression analyses were conducted using R statistical software to identify determinants affecting knowledge on age-related macular degeneration risk factors. The strength and precision of relationships between the outcome and the factors were quantified using adjusted odds ratios with 95% confidence intervals. P - value below 5% was used to declare statistically significance associations.<br><br>RESULTS: Six hundred seven healthcare professionals took part in this study. Less than one-third of the participants (29.7%; 95% CI: 25.0%, 34.8%) showed adequate knowledge of risk factors of age-related macular degeneration. Male sex (AOR: 1.68; 95% CI: 1.16, 2.43), healthcare service experience less than five years (AOR: 1.86; 95% CI: 1.23, 2.88), ten years of experience in healthcare (AOR: 0.57; 95% CI: 0.34, 0.95), eye health-related training (AOR: 1.91; 95% CI: 1.23, 2.83), hypertension history (AOR: 2.28; 95% CI: 1.52, 3.44) and diabetes mellitus (AOR: 2.48; 95% CI: 1.02, 6.27) determine healthcare professionals' knowledge of age-related macular degeneration risk factors.<br><br>CONCLUSION: The study highlights a significant knowledge gap among healthcare professionals regarding age-related macular degeneration risk factors. Gender, years of experience in healthcare, and receiving eye health-related training are key determinates of knowledge on age-related macular degeneration risk factors, underscoring the importance of directed educational and trainings to improve healthcare professionals' knowledge on age-related macular degeneration risk factors.},
}
@article {pmid40487113,
year = {2025},
author = {Patel, HP and Robbins, CB and Karl, JJ and Weng, P and Vajzovic, L and Fekrat, S},
title = {Oral Antithrombotic Medication Is Associated with Improved Visual Outcomes in Eyes with Submacular Hemorrhage from Wet Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100796},
pmid = {40487113},
issn = {2666-9145},
abstract = {PURPOSE: To determine differences in visual acuity (VA) outcomes in eyes of patients on antithrombotics (antiplatelet agents and anticoagulants) that develop submacular hemorrhage (SMH) compared with eyes of patients who are not on antithrombotics and develop SMH.<br><br>DESIGN: A retrospective study of patients presenting with fovea-involving SMH due to wet age-related macular degeneration over an 8-year period who had &#x2265;6 months of follow-up.<br><br>SUBJECTS: Demographics, VA at presentation and final follow-up after SMH management, and history of any antithrombotic therapy were collected. Patients were grouped based on whether they were on anticoagulants (direct oral anticoagulants or warfarin), antiplatelet agents (P2Y12 inhibitors, aspirin, or both), or neither.<br><br>METHODS: Multivariate generalized estimating equations were used for statistical analysis.<br><br>MAIN OUTCOME MEASURES: The difference between VA at presentation with SMH and VA at final follow-up was compared between patients taking oral anticoagulants or antiplatelet agents and those not on any antithrombotic agent.<br><br>RESULTS: Seventy-seven eyes of 74 patients were included. Twenty were on oral anticoagulants, 38 were on antiplatelet agents, and 22 were on neither. After controlling for age, sex, post-SMH cataract surgery, time to presentation, treatments received, initial VA, and follow-up duration, patients taking oral anticoagulants had greater improvement in VA at final follow-up compared with patients who were not taking a concurrent antithrombotic agent (P = 0.001); however, patients on oral antiplatelets did not (P = 0.09). After additionally controlling for the initial size and thickness of SMH, patients taking oral anticoagulants and patients taking oral antiplatelets had greater improvement in VA at final follow-up compared with patients who were not taking an antithrombotic (P = 0.002 and P < 0.001, respectively).<br><br>CONCLUSIONS: Patients taking oral anticoagulants who then develop an SMH may have better long-term VA outcomes than those who were not. However, this effect was not seen in patients taking oral antiplatelet medications. This suggests that baseline anticoagulants may be associated with improved VA outcomes in eyes that develop an SMH. When controlling for size and thickness of SMH, patients taking oral anticoagulants and those taking oral antiplatelets had better long-term VA outcomes than those who were not, suggesting a potential mitigating effect of oral antithrombotics.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40484741,
year = {2025},
author = {Ma, Y and Lin, Q and He, HL and Liu, YX and Li, M and Zhang, XH and Jin, ZB},
title = {Juvenile macular degeneration in nonhuman primates generated by germline knockout of ABCA4 gene.},
journal = {Science bulletin},
volume = {70},
number = {14},
pages = {2237-2240},
doi = {10.1016/j.scib.2025.04.077},
pmid = {40484741},
issn = {2095-9281},
}
@article {pmid40484678,
year = {2025},
author = {Obayashi, M and Otsu, W and Yamazaki, K and Nakamura, S and Ishikawa, H and Sakata, Y and Tsuboi, M and Tsusaki, H and Shimazawa, M},
title = {Pentadecyl, an Active Component of Microalgae, Ameliorates Endoplasmic Reticulum Stress and Blue Light-Induced Cell Death in Mouse Retina-Derived 661W Cells.},
journal = {Biological &amp; pharmaceutical bulletin},
volume = {48},
number = {6},
pages = {791-800},
doi = {10.1248/bpb.b24-00889},
pmid = {40484678},
issn = {1347-5215},
mesh = {*Endoplasmic Reticulum Stress/drug effects/radiation effects ; Animals ; *Light/adverse effects ; Mice ; Activating Transcription Factor 4/metabolism/genetics ; Cell Death/drug effects/radiation effects ; Cell Line ; *Microalgae/chemistry ; *Retina/drug effects/cytology/radiation effects ; Oxidative Stress/drug effects ; Tunicamycin/pharmacology ; Unfolded Protein Response/drug effects ; Hydrogen Peroxide ; Blue Light ; },
abstract = {Light stress is a risk factor leading to retinal diseases such as age-related macular degeneration. However, the mechanism underlying the stress response to light in the retina has yet to be elucidated. We have reported that exposure to blue light-emitting diode light induces excessive production of reactive oxygen species and activates the unfolded protein response, robustly increasing activating transcription factor 4 (ATF4) expression. These processes result in photoreceptor cell death. This study investigates the effects of Pentadecyl, a bioactive product obtained from Aurantiochytrium limacinum, on either chemical-induced or blue light-induced endoplasmic reticulum (ER) stress. Pentadecyl suppressed cell death induced by either thapsigargin or tunicamycin in a concentration-dependent manner. Pentadecyl also suppressed the expression of unfolded protein response target genes, including Atf4 and ER chaperones. Consistently, immunoblotting revealed that Pentadecyl suppressed the increased expression of ATF4 at the protein level. Pentadecyl also protected 661W cells from blue light-induced damage but did not protect against hydrogen peroxide (H2O2)-induced oxidative stress. These results indicated that Pentadecyl has a novel function that protects against ER stress induced by photodamage.},
}
@article {pmid40484298,
year = {2025},
author = {Berni, A and Foti, C and Ulla, L and Vyas, C and Chhablani, J and Chaudhary, V and Subhi, Y and Gregori, G and Wang, RK and Rosenfeld, PJ and Sadda, SR and Bandello, F and Reibaldi, M and Borrelli, E},
title = {Choriocapillaris in Age-Related Macular Degeneration: A Systematic Review of Optical Coherence Tomography Angiography-Based Assessments and Challenges in Standardization.},
journal = {American journal of ophthalmology},
volume = {277},
number = {},
pages = {482-496},
doi = {10.1016/j.ajo.2025.05.051},
pmid = {40484298},
issn = {1879-1891},
mesh = {Humans ; *Tomography, Optical Coherence/methods/standards ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods/standards ; *Macular Degeneration/diagnostic imaging/physiopathology/diagnosis ; *Capillaries/diagnostic imaging/pathology ; *Retinal Vessels/diagnostic imaging ; },
abstract = {TOPIC: This systematic review evaluates the methodologies used for assessing the choriocapillaris (CC) in age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). It focuses on identifying methodological heterogeneity in imaging and analysis protocols and its implications for clinical and research applications.<br><br>CLINICAL RELEVANCE: AMD is a leading cause of vision loss, and assessing CC perfusion provides critical insights into its pathophysiology. OCTA has emerged as a noninvasive imaging technique offering high-resolution visualization of the CC. However, variability in methodologies has hindered the standardization of CC assessments. Establishing consistent practices is essential for improving clinical and research outcomes in AMD management.<br><br>DESIGN: Systematic review.<br><br>METHODS: Studies included in this review were selected on the basis of eligibility criteria defined by the Population, Intervention, Comparator, Outcome, Study design framework. Participants included patients with early, intermediate, and late AMD. Interventions involved the use of OCTA for CC assessment, with no restrictions on device type or scan parameters. Comprehensive searches of MEDLINE, Web of Science Core Collection, and the Cochrane Library were conducted up to November 30, 2024. Data extractions and narrative synthesis focused on device types, scan protocols, segmentation techniques, compensation strategies, and quantitative metrics.<br><br>RESULTS: A total of 102 studies, encompassing 4047 patients with AMD and 4415 eyes, were analyzed. Fifty-two studies used spectral-domain OCTA, and 49 studies used swept-source OCTA, with significant heterogeneity in segmentation boundaries and slab thickness (4.4-30 &#xb5;m). Only 32 studies used compensation strategies to address signal attenuation under drusen. Quantitative metrics varied widely, with CC flow deficit percentage being the most common. However, inconsistencies in thresholding methods and lack of standardized Phansalkar radius reporting limited comparability. The review highlights gaps in reporting segmentation boundaries and compensation techniques, which impact the ability to assess the reliability of findings.<br><br>CONCLUSIONS: This review underscores substantial variability in methodologies for CC assessment in AMD, highlighting the urgent need for standardized imaging protocols and analytical approaches. Despite advances in OCTA technology, inconsistencies in segmentation, thresholding, and compensation strategies challenge data reliability and reproducibility. Future research should prioritize methodological standardization to enhance comparability and clinical applicability.},
}
@article {pmid40481786,
year = {2025},
author = {Falemban, AH and Söderberg-Löfdal, K and Jonsson, F and Almlöf-Sarman, S and von Euler, M and Westborg, I},
title = {Intravitreal anti-vascular endothelial growth factor injections and risks of stroke in patients with neovascular age-related macular degeneration-A registry-based cohort study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.17534},
pmid = {40481786},
issn = {1755-3768},
support = {//Region Stockholm/ ; },
abstract = {BACKGROUND: Intravitreal Anti-Vascular Endothelial Growth Factor (VEGF) rescues retinal vasculatures and prevents disease progression in patients with neovascular Age-Related Macular Degeneration (nAMD). However, systemic anti-VEGF may increase the risk of thromboembolic related complications including stroke and TIA. This study aims to explore the association between stroke and intravitreal anti-VEGF agents; ranibizumab, aflibercept and bevacizumab.<br><br>METHODS: This nationwide, population- registry-based case-control study used registered data 2007-2019. Data from the Swedish Stroke Registry (Riksstroke) and the Swedish Macula Register (SMR) were cross-linked to identify nAMD patients who developed stroke/TIA within 90&#x2009;days after intravitreal anti-VEGF injection. Each stroke case was matched with three controls from Riksstroke with stroke/TIA but no anti-VEGF treatment.<br><br>RESULTS: A total of 33&#x2009;585 patients with nAMD underwent intravitreal anti-VEGF agent injections. A stroke occurred in 1693 patients of this group, and 936 of them within 90&#x2009;days of treatment. Compared with nonuse, intravitreal anti-VEGF agent use was associated with an increased risk of stroke within 90&#x2009;days of anti-VEGF treatment in 2.9% of the nAMD-patients [Risk Ratio (RR) 1.27, 95% confidence interval (CI) 1.22; 1.33] compared to non-users. The RR within 30, 31-60 and 61-90&#x2009;days were 1.36 (1.15; 1.66), 1.40 (1.09; 1.79) and 0.58 (0.52; 0.65), respectively.<br><br>CONCLUSIONS: Even though the risk is small, intravitreal injections with anti-VEGF agents for the treatment of nAMD are associated with an increased risk of stroke/TIA. The risk seems to be higher within 60&#x2009;days of last injection. An assessment of high-risk populations and risk-benefit weighting is necessary before intravitreal anti-VEGF injections are considered.},
}
@article {pmid40479828,
year = {2025},
author = {Sansare, Y and Kejamurthy, P and Singh, S and Ayush, A and Khani, K and Ramya Devi, KT},
title = {Aptamers as therapeutic targets: prospects and progress in the treatment of cancers.},
journal = {Nucleosides, nucleotides &amp; nucleic acids},
volume = {},
number = {},
pages = {1-39},
doi = {10.1080/15257770.2025.2512853},
pmid = {40479828},
issn = {1532-2335},
abstract = {Contemporary cancer treatments encompass diverse strategies like surgery, chemotherapy, radiation, immunotherapy, and targeted therapies, aiming for effective cancer cell control with minimal impact on healthy tissues. Aptamers are short nucleotide sequences typically containing 25-80 bases and can attach to specific target molecules as effectively as monoclonal antibodies. While the FDA has yet to approve any aptamers for oncology applications, a few, such as Pegaptanib (Macugen), have been approved for ophthalmologic conditions like age-related macular degeneration. Pegaptanib and Izervay are the approved aptamers against age-related macular degeneration (AMD) that target vascular endothelial growth factor (VEGF) and block complement component protein C5, respectively. A new type of highly sensitive and specific biosensor has recently been created to detect leukaemia cancer cells. Aptamosomes, encapsulating drugs like doxorubicin, effectively reduce tumour size and are highly advantageous over targeted drug delivery. Many aptamers have been generated against ERα, Epithelial cell adhesion molecule, EGFR, B subunit of platelet-derived growth factor, Vimentin, Osteopontin, Type II membrane protein PSMA, MUC-1, AXL receptor tyrosine kinase, CD28 agonistic aptamer, as well as for the B7-CD28 interaction, etc. This review suggests the pros and cons of aptamer usage and its advantages over antibody treatment. It also outlines the roles of aptamers and connects their modes of action with specific cancer types. The content is highly detailed, providing a comprehensive understanding of aptamer therapy and its applications.},
}
@article {pmid40478589,
year = {2025},
author = {Won, J and Yaghy, A and Ploner, SB and Kaiser, S and Girgis, JM and Hwang, Y and Jamil, MU and Maier, A and Waheed, NK and Fujimoto, JG},
title = {High-Resolution, Motion-Corrected, Volume-Fused OCT for Investigating Longitudinal Changes in Subretinal Drusenoid Deposits in Intermediate AMD.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {6},
pages = {15},
pmid = {40478589},
issn = {2164-2591},
support = {R01 EY011289/EY/NEI NIH HHS/United States ; R01 EY034080/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; Aged ; Male ; Female ; Motion ; Middle Aged ; Aged, 80 and over ; },
abstract = {PURPOSE: To demonstrate high-resolution, motion-corrected, volume-fused optical coherence tomography (OCT) for assessing longitudinal changes in macular dot form subretinal drusenoid deposits (SDDs).<br><br>METHODS: Six consecutive isotropic volume raster scans over 6 &#xd7; 6&#xa0;mm (500 &#xd7; 500 A-scans) were acquired using a high-resolution (2.7 &#xb5;m axial resolution) spectral domain OCT prototype instrument. OCT volumes were computationally motion-corrected and fused. The distribution and longitudinal changes in dot SDDs were evaluated using en face OCT in a 50-&#xb5;m-thick slab, from 27 &#xb5;m above Bruch's membrane.<br><br>RESULTS: Computational motion correction and volume fusion methods improve visibility of small en face features and compensate for motion artifacts to facilitate longitudinal assessment. In total, 326 SDDs were identified in a representative series of four eyes from four patients with intermediate age-related macular degeneration (AMD) and assessed with a 3- to 12-month follow-up. Of the SDDs, 85.3% remained stable over the follow-up, while 9.8% regressed, 3.4% fused, and 1.5% new SDDs appeared.<br><br>CONCLUSIONS: Computational motion correction and volume fusion combined with high-resolution OCT B-scans and en face slabs facilitate visualization and longitudinal tracking of focal pathologies, such as SDDs.<br><br>TRANSLATIONAL RELEVANCE: The methods presented have the potential to improve OCT analysis of focal features, such as quantification of SDDs and other AMD biomarkers.},
}
@article {pmid40478389,
year = {2025},
author = {Banerjee, M and Moharana, S and Padhy, SK},
title = {Systemic Effects of Intravitreal Anti-VEGF Therapy: A Review of Safety across Organ Systems.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {8},
pages = {1661-1684},
pmid = {40478389},
issn = {2193-8245},
support = {Intramural Grant//Hyderabad Eye Research Foundation/ ; },
abstract = {Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have transformed the management of retinal diseases such as diabetic macular edema and neovascular age-related macular degeneration. However, concerns about their systemic absorption and potential adverse effects on overall health remain. In this review, we systematically aggregate existing literature on the systemic impact of anti-VEGF therapy, with a detailed analysis of the pharmacodynamics and pharmacokinetics of individual drugs. By examining their metabolism, clearance, and systemic exposure, we aim to clarify the extent of their effects beyond the eye. We further explore their influence on renal and cardiovascular health, with evidence suggesting a generally safe profile in the short term but potential risks in high-risk patients, particularly those with preexisting kidney or heart conditions. Additionally, this review addresses the critical concerns surrounding anti-VEGF use in special populations, including pregnant and lactating women and neonates with retinopathy of prematurity (ROP). We discuss the potential risks, the safest options available, and precautionary measures that should be taken when administering these therapies in these groups. While anti-VEGFs remain an essential tool in ophthalmology, careful patient selection, monitoring, and individualized treatment approaches are necessary to mitigate potential systemic risks. Further research is needed to refine our understanding of long-term safety.},
}
@article {pmid40474962,
year = {2025},
author = {Mat Nor, MN and Green, CR and Squirrell, D and Acosta, ML},
title = {Retinal Hyperreflective Foci Are Biomarkers of Ocular Disease: A Scoping Review With Evidence From Humans and Insights From Animal Models.},
journal = {Journal of ophthalmology},
volume = {2025},
number = {},
pages = {9573587},
pmid = {40474962},
issn = {2090-004X},
abstract = {Background: Abnormalities in the retina have a profound impact on vision, and accurate diagnosis and monitoring are essential for effective clinical management. Retinal hyperreflective foci (HRF), lesions, or dots, identified using optical coherence tomography (OCT), are observed in both animals and humans and have been associated with several ocular conditions, including diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vascular diseases. Methods: To evaluate the relevance of retinal HRF, we conducted a comprehensive scoping review of the literature published up to July 2024 including in the discussion key papers that emerged in 2025. Our search spanned electronic databases utilizing carefully identified search terms related to HRF and OCT within the last six years. We excluded publications on HRF outside the retina, treatments, non-peer-reviewed content, duplicates, studies older than 6 years, and those not focused on AMD, DR, or glaucoma. Results: A total of 141,085 records were initially identified from various databases and further refined based on keywords and content relevance. Finally, 42 reports meeting the criteria were retained for in-depth analysis. HRF were observed mainly in OCT scans of the AMD retina, as well as in DR and, to a lesser extent, in other retinopathies and interestingly in glaucoma. In AMD, HRF are described as a marker for disease progression, often associated with a compromised photoreceptor structure. In DR, HRF indicated issues such as abnormal blood vessels and cellular changes linked to microglia activation. In glaucoma, HRF may reflect microglia and macrophage activation. Most publications concur that the presence of HRF correlates with inflammatory processes and aging in the retina, with early appearance of small HRF serving as a biomarker for ocular disease. The size of HRF and their location were consistent with disease presentation. Conclusion: There is an agreement that HRF of less than 30 μm are biomarkers of inflammation in the retina despite having variable intraretinal locations. HRF resulting from the effect of aging can be discerned from AMD based on their quantity and appearance. The results show the importance of HRF as a biomarker of ocular disease and confirm that HRF are indicative of an inflammatory eye disorder.},
}
@article {pmid40473932,
year = {2025},
author = {Zarranz-Ventura, J and Marías-Pérez, S and Martin-Pinardel, R and Fernandez-Bonet, M and Pina-Marin, B and Cobos, E and Rodríguez-Fernandez, CA and Parrado-Carrillo, A and Alarcón-Valero, I and Barnes, C and Cilveti, E and Aramburu-Claveria, J and Ascaso-Puyuelo, FJ and Calvo, P and Ruiz-Del-Tiempo, MP and Susanna-González, G and Figueras-Roca, M and Casaroli-Marano, RP and Bernal-Morales, C and , },
title = {Brolucizumab clinical and safety outcomes in a neovascular age-related macular degeneration national database: Fight Retinal Blindness Spain (FRB Spain).},
journal = {Eye (London, England)},
volume = {39},
number = {12},
pages = {2407-2414},
pmid = {40473932},
issn = {1476-5454},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Databases, Factual ; Follow-Up Studies ; Intravitreal Injections ; Spain/epidemiology ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; },
abstract = {AIM: To evaluate clinical outcomes, treatment intervals, and safety outcomes of brolucizumab (BRO) treatment in a national neovascular age-related macular degeneration (nAMD) database.<br><br>METHODS: Multicentre, national, routine clinical care database study of nAMD eyes receiving &#x2265;1 BRO injection. Demographics, visual acuity (VA) measured in logMAR letters, macular neovascularization (MNV) activity, number of injections, visit data and information on any adverse events were collected at baseline and at 3, 6, 9 and 12 months after BRO initiation for each patient/eye.<br><br>RESULTS: A total of 305 eyes received &#x2265; 1 BRO injection and 214 eyes (14% na&#xef;ve, 86% switchers) completed &#x2265; 3 months follow-up. In switchers, the percentage of eyes extended to &#x2265;8 week intervals at 3/6/9 months was 43.2%/45.7%/54.5% and to &#x2265;10 week intervals was 12.9%/18.5%/13.6%, respectively. Eyes with VA&#x2009;&#x2265;&#x2009;70 increased from 36% at baseline to 48% at 3 months and 50% at 9 months. MNV lesion activity status decreased from 94% (active/active-only SRF, 46/48%) at baseline to 56% (21/35%), 61% (23/38%), 76% (27/49%) and 65% (24/41%) at months 3/6/9 and 12, respectively. Adverse effects were observed in 6.5% of the treated eyes, being the most prevalent anterior uveitis (3.2%), vitritis (4.5%) and vasculitis (2.2%).<br><br>CONCLUSION: In this series BRO achieves an extension in the treatment intervals in half of the patients which require frequent reinjections (<8 weekly), reducing MNV activity in a third of this specific difficult-to-treat subgroup. The adverse event rates described are consistent with other cohorts and need to be considered to inform treatment decisions in case-by-case discussions.},
}
@article {pmid40473146,
year = {2025},
author = {Qi, CC and Wang, XS and Zhang, Z and Chen, L and Song, WC and Wang, JH and Zhu, Y and Guo, S and Su, SL and Duan, JA},
title = {JuJing formula protects retinal by regulating Nrf2/HO-1 pathways and sphingolipid rheostat and its key protein levels on liver-kidney Yin deficient retinal damage mice.},
journal = {Journal of ethnopharmacology},
volume = {351},
number = {},
pages = {120085},
doi = {10.1016/j.jep.2025.120085},
pmid = {40473146},
issn = {1872-7573},
mesh = {Animals ; Mice ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *NF-E2-Related Factor 2/metabolism ; *Retina/drug effects/pathology/metabolism ; Male ; Liver/drug effects/metabolism/pathology ; Disease Models, Animal ; Oxidative Stress/drug effects ; *Sphingolipids/metabolism ; Signal Transduction/drug effects ; *Yin Deficiency/drug therapy/metabolism ; Mice, Inbred C57BL ; Kidney/drug effects/metabolism/pathology ; Heme Oxygenase-1/metabolism ; Membrane Proteins/metabolism ; },
abstract = {Dry age-related macular degeneration (AMD) has a high rate of blindness, which still lacks effective treatment. JuJing Formula (JJF) is a traditional herbal prescription known for its hepatorenal tonic effects and therapeutic applications in ocular disorders. Previous investigations have demonstrated its efficacy in the management of dry AMD. However, the underlying mechanisms of JJF against dry AMD have not been fully characterized.<br><br>AIM OF THE STUDY: The protective effect and mechanism of JJF on dry AMD were investigated in the liver-kidney Yin deficient retinal damage (LKYD-RD) model of mice.<br><br>MATERIALS AND METHODS: Initially, a LKYD-RD mouse model was established through a combination of thyroxine administration, tail clamping, and sodium iodate injection. Secondly, the amelioration of Yin deficiency symptoms was examined by detecting biochemical indices and histopathologic changes. Meanwhile, the therapeutic efficacy on retinal damage was evaluated using optical coherence tomography (OCT), hematoxylin and eosin (H&amp;E) staining, terminal deoxynucleotidyl (TUNEL) staining, and levels of oxidative stress markers (SOD, MDA, and GSH) and inflammatory factors (IL-1&#x3b2;, IL-6, and TNF-&#x3b1;). Furthermore, serum metabolomics studies were performed to predict the mechanisms of JJF on LKYD-RD mice. Eventually, ELISA, immunofluorescence analysis, RT-qPCR, and Western blotting assays were conducted to verify the mechanisms.<br><br>RESULTS: JJF not only significantly ameliorated LKYD syndrome but also restored the retinal structure and function in LKYD-RD mice. Furthermore, JJF inhibited the inflammatory response and suppressed oxidative stress through the Nrf2/HO-1 signaling pathway. Metabolomic profiling revealed sphingolipid signaling as the predominant regulatory pathway mediating JJF's therapeutic effects on LKYD-RD. Specifically, JJF treatment normalized sphingolipid metabolism by reducing elevated ocular levels of ceramide and sphingosine while increasing sphingosine-1-phosphate concentrations. At the molecular level, JJF upregulated the expression of p-Sphk1/Sphk1, Asah1, and Bcl2, while downregulating Cers2, Cers6, Bax, cleaved-Caspase 3, and Sgpp1. The findings suggested that regulation of the sphingolipid rheostat and its critical proteins is a potential mechanism of JJF resistance to dry AMD.<br><br>CONCLUSIONS: In summary, the current study demonstrates that JJF exerts significant therapeutic effects in the LKYD-RD murine model, primarily through the modulation of sphingolipid metabolic signaling pathways. This research provides a reference for the clinical management of dry AMD.},
}
@article {pmid40473035,
year = {2025},
author = {Hyttinen, JMT and Niittykoski, M and Kaarniranta, K},
title = {The role of secretory autophagy and exosomes in the accumulation of drusen during the development of age-related macular degeneration (AMD).},
journal = {Ageing research reviews},
volume = {110},
number = {},
pages = {102796},
doi = {10.1016/j.arr.2025.102796},
pmid = {40473035},
issn = {1872-9649},
mesh = {Humans ; *Autophagy/physiology ; *Exosomes/metabolism ; *Macular Degeneration/pathology/metabolism ; *Retinal Drusen/pathology/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is the most common disease of the elderly that leads to the loss of sight. So far, no satisfactory therapy exists for this complex eye disease. The appearance of extracellular deposits, called drusen, on the outside of the retinal pigment epithelium (RPE) is considered to be the main clinical hallmark of AMD. Whilst the mechanisms of drusen formation are not well known, secreted material from the RPE, during its degeneration, is thought to contribute to the development of AMD. Various unconventional protein secretion (UPS) pathways are considered to be routes for the delivery of material which form the drusen. The two main forms of UPS are secretory autophagy, which is responsible for the cleansing of cellular debris from the RPE cells and endosomal secretion which carries material outside of the cell via exosomes. These pathways are unconventional in the sense that they comprise the delivery of material to the exterior of cells by bypassing the Golgi apparatus. Although secretory autophagy and exosome release are regarded as different routes by which cells exude material, they share similarities, such as common molecular participants and that their routes converge. Therefore, manipulation of these two processes might be useful in a therapy against AMD by diminishing the destructive drusen progression in the vicinity of the RPE.},
}
@article {pmid40471752,
year = {2025},
author = {Tan, NRX and Chan, KE and Lim, BXH and Giannaccare, G and Najjar, RP and Lim, CHL},
title = {Photobiomodulation: evidence and applications in ophthalmology.},
journal = {Current opinion in ophthalmology},
volume = {36},
number = {5},
pages = {345-381},
doi = {10.1097/ICU.0000000000001154},
pmid = {40471752},
issn = {1531-7021},
mesh = {Humans ; *Low-Level Light Therapy/methods ; *Ophthalmology/methods ; *Eye Diseases/radiotherapy ; },
abstract = {PURPOSE OF REVIEW: Photobiomodulation (PBM) is a noninvasive therapy utilising low-level light energy to stimulate cellular processes, modulate inflammatory pathways, enhance mitochondrial activity, promote tissue regeneration. With growing interest in PBM as a potential treatment modality, this review synthesises current evidence and highlights challenges of implementing PBM across various ophthalmic conditions.<br><br>RECENT FINDINGS: Current ophthalmic applications of PBM can be categorised into established and exploratory therapies, differentiated primarily by the attainment of regulatory approval. Established applications of PBM include the treatment of dry eye disease and nonexudative age-related macular degeneration, while the use of PBM is still largely exploratory in conditions such as diabetic macular oedema and retinopathy of prematurity. Regardless of the level of regulatory authorisation, the application of PBM in each ophthalmic condition presents with distinct challenges requiring further research for comprehensive validation.<br><br>SUMMARY: While PBM holds promise as a novel therapeutic option, its long-term efficacy and safety remains to be fully established. Standardised treatment guidelines and larger randomised controlled trials are essential to optimise its use in future clinical practice.},
}
@article {pmid40471562,
year = {2025},
author = {Shor, R and Mihalache, A and Noori, A and Shor, R and Kohly, RP and Popovic, MM and Muni, RH},
title = {Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {143},
number = {7},
pages = {587-594},
pmid = {40471562},
issn = {2168-6173},
mesh = {Humans ; Female ; Retrospective Studies ; Aged ; Male ; *Glucagon-Like Peptide-1 Receptor Agonists ; *Hypoglycemic Agents/adverse effects/therapeutic use ; Ontario/epidemiology ; *Wet Macular Degeneration/epidemiology/chemically induced/diagnosis ; Follow-Up Studies ; Incidence ; Risk Factors ; Aged, 80 and over ; Diabetes Mellitus, Type 2/drug therapy ; },
abstract = {IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are extensively used in treating diabetes and obesity, yet little is known about the long-term ocular effects of systemic prolonged exposure.<br><br>OBJECTIVE: To evaluate the risk of developing neovascular age-related macular degeneration (nAMD) associated with the use of GLP-1 RAs in patients with diabetes.<br><br>This population-based, retrospective cohort study was conducted from January 2020 to November 2023, with a follow-up period of 3 years. Data analysis was performed from August 2024 to October 2024. The investigators used comprehensive administrative health and demographic data from patients in Ontario, Canada, which were collected by the Institute for Clinical Evaluative Sciences in the context of a universal public health care system. Inclusion criteria were patients aged 66 years or older with a diagnosis of diabetes and a minimum follow-up period of 12 months following initial diabetes diagnosis. Patients with incomplete Ontario Health Insurance Plan or Ontario Drug Benefit data or patients exposed to GLP-1 RA for less than 6 months were excluded. Of 1&#x202f;119&#x202f;517 eligible patients, a 1:2 matched cohort of 139&#x202f;002 patients was created, including 46&#x202f;334 patients who were exposed to GLP-1 RAs and 92&#x202f;668 unexposed matched patients. Systemic comorbidities that were associated with any kind of AMD and socioeconomic status were used to calculate propensity scores.<br><br>EXPOSURE: GLP-1 RA use for 6 months or longer.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence and time to event of nAMD during the follow-up period.<br><br>RESULTS: Among 139&#x202f;002 matched patients, mean (SD) patient age was 66.2 (7.5) years, and 64&#x202f;775 patients (46.6%) were women. The incidence of nAMD was higher among the exposed cohort than among the unexposed cohort. Cox proportional hazard models, both unadjusted (crude) and adjusted, estimated hazard ratios for nAMD development of greater than 2.0 among patients exposed to GLP-1 RAs (exposed, 0.2% vs unexposed, 0.1%; difference, 0.1%; crude: HR, 2.11; 95% CI, 1.58-2.82; adjusted: HR, 2.21; 95% CI, 1.65-2.96).<br><br>CONCLUSIONS AND RELEVANCE: In this cohort study, the use of GLP-1 RAs among patients with diabetes was associated with a 2-fold higher risk of incident nAMD development than among similar patients with diabetes who did not receive a GLP-1 RA. Further research is needed to elucidate the exact pathophysiological mechanisms involved and to understand the trade-offs between the benefits and risks of GLP-1 RAs.},
}
@article {pmid40470323,
year = {2025},
author = {Zhang, G and Qu, Y and Wan, X and Fang, X and Wu, Y and Li, T and Sun, J and Liu, X and Xu, Y and Luo, H and Meng, X and Hu, W and Chen, R and Wu, Z and Jia, H and Sun, X},
title = {Ozone exposure and increased risk of age-related macular degeneration: Evidence from nationwide cohort and toxicological studies.},
journal = {Innovation (Cambridge (Mass.))},
volume = {6},
number = {4},
pages = {100808},
pmid = {40470323},
issn = {2666-6758},
abstract = {Evidence regarding the impact of ozone on age-related macular degeneration (AMD) remains limited. We conducted a nationwide cohort analysis of 27,923 participants in China, along with a random control animal toxicological study, to elucidate the temporal relationship between ozone exposure and AMD as well as the underlying biological explanation. In the population study, 5,149 participants were diagnosed with incident AMD during a 348,701 person-month follow-up. The participants were divided into low-, medium-, and high-exposure groups. Fully adjusted Cox regression models showed that the risk of AMD increased by 28% for the medium- and 101% for the high-exposure groups relative to the low-exposure group (p for trend < 0.001). The exposure-response curves exhibited a J-shaped trend. Sensitivity analyses confirmed these results, revealing stronger associations among participants older than 65 years old and those living in rural or northern China. In the toxicological study, the mice were randomized to inhale ozone or filtered air, and those exposed to ozone had photoreceptor damage and vision impairment, which are hallmarks of AMD. We further clarified that ozone exposure contributes to AMD by activating systemic inflammation and detailing how external air-pollutant-induced inflammation factors reach the retina, which is the innermost layer of the eye, and cause retinal disease. Our comprehensive studies provide key evidence on the temporal relationship between ozone exposure and increased AMD risk, suggesting the visual health benefits of collaboratively enforcing necessary ozone pollution control policies, especially in regions with high ozone concentrations, within the context of a globally aging population.},
}
@article {pmid40469929,
year = {2025},
author = {Kawasaki, A and Yuki, M and Nakagawa, S and Iwasaki, K and Ochi, H and Sugitani, Y},
title = {Patient Preference on Age-Related Macular Degeneration Treatment: A Systematic Review.},
journal = {Patient preference and adherence},
volume = {19},
number = {},
pages = {1639-1652},
pmid = {40469929},
issn = {1177-889X},
abstract = {PURPOSE: Patient preference is important in decision-making processes, such as drug approval and price determination. We conducted a systematic review regarding the preference of age-related macular degeneration (AMD) treatment.<br><br>PATIENTS AND METHODS: We searched for articles on patient preferences for AMD treatment published between January 1, 2000 and December 31, 2023 using EMBASE, Google scholar, MEDLINE, and PLOS.<br><br>RESULTS: Seven studies were included in this systematic review. Conjoint analysis was used in all seven trials, of which six were Discrete Choice Experiments and one was a ranking. These studies were conducted in Germany, United States, United Kingdom, Japan, Spain, and Singapore. Six studies focused on patients with neovascular AMD (nAMD, also called wet AMD, ie, wAMD), and one focused on patients with nAMD or diabetic macular edema. The attributes of the treatments used in these seven studies were efficacy, safety, convenience, and cost. Overall, the relative importance of attributes related to efficacy and safety were the highest, followed by those related to convenience and costs. The convenience and cost attributes were almost equal.<br><br>CONCLUSION: Although the definitions of treatment attributes differed among the studies, patients with nAMD considered efficacy and safety to be the most important. The results of several studies suggest that patient preferences may be affected by patient demographics, such as sex. Although there are currently only a few preference studies on patients with AMD, it is necessary to continue conducting studies to understand the trends in patient preferences according to patient demographics.},
}
@article {pmid40469898,
year = {2025},
author = {Wu, Z and Sadda, SR and Ach, T and Blodi, BA and Bottoni, F and Chakravarthy, U and Chew, EY and Curcio, CA and Ferris, FL and Fleckenstein, M and Freund, KB and Grunwald, JE and Holz, FG and Jaffe, GJ and Liakopoulos, S and Lim, TH and Monés, JM and Pagliarini, S and Pauleikhoff, D and Pfau, M and Rosenfeld, PJ and Sarraf, D and Schmitz-Valckenberg, S and Spaide, RF and Sparrow, JR and Staurenghi, G and Tufail, A and Viola, F and Guymer, RH},
title = {Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point-A Delphi Study: Classification of Atrophy Meetings Report 7.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100777},
pmid = {40469898},
issn = {2666-9145},
abstract = {PURPOSE: To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point.<br><br>DESIGN: A modified Delphi study.<br><br>PARTICIPANTS: International panel of experts in AMD, retinal imaging, and histopathology that are part of the Classification of Atrophy Meetings group.<br><br>METHODS: A modified Delphi study was undertaken to determine if there is consensus on the acceptability of the onset of end-stage atrophic AMD as a clinical end point to evaluate early interventions and the criteria for defining such an end point. Two initial rounds of online surveys were conducted. Aggregate results and anonymized comments were provided after each round, followed by a face-to-face meeting before a final survey round was completed.<br><br>MAIN OUTCOME MEASURES: Statements where consensus was reached, defined as &#x2265;80% of responses within the 3-point bracket for agreement or disagreement based on a 9-point Likert rating scale, from a total of 33 statements included in the final round of the survey.<br><br>RESULTS: Consensus was reached for the statement that the onset of end-stage atrophic AMD was an appropriate clinical end point to evaluate early interventions (82% responses in agreement). Consensus was also reached for the statement that such an end point should be defined based on anatomical changes that have been previously shown in clinical studies to be associated with marked, but not necessarily complete, functional loss (95% responses in agreement). Consensus was nearly reached for the specific criterion that &#x2265;90% of such atrophic AMD lesions should have &#x2265;1 test location that was &#x2264;10&#xa0;decibels on 2 microperimetry tests (77% responses in agreement).<br><br>CONCLUSIONS: There was expert group consensus that the onset of end-stage atrophy is an appropriate clinical end point to evaluate early interventions in AMD, and that such an end point should show evidence of marked functional loss in prior clinical studies. We believe these findings will help to define incident clinical end points that are acceptable to regulatory authorities.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40468952,
year = {2025},
author = {Lu, Y and Tan, Y and Jin, K and Xiong, W},
title = {Assessing the relationship between different sleep traits and retinal neurodegenerative diseases: A bidirectional Mendelian randomization study.},
journal = {Chronobiology international},
volume = {42},
number = {6},
pages = {784-794},
doi = {10.1080/07420528.2025.2509631},
pmid = {40468952},
issn = {1525-6073},
mesh = {Humans ; Mendelian Randomization Analysis ; *Sleep/genetics/physiology ; Genome-Wide Association Study ; *Neurodegenerative Diseases/genetics/physiopathology ; Risk Factors ; *Circadian Rhythm/genetics/physiology ; Macular Degeneration/genetics/physiopathology ; Male ; Female ; *Diabetic Retinopathy/genetics/physiopathology ; Polymorphism, Single Nucleotide ; Middle Aged ; Aged ; Glaucoma, Open-Angle/genetics/physiopathology ; },
abstract = {his bidirectional Mendelian randomization (MR) study assessed causal relationships between sleep traits (chronotype, sleep duration, insomnia) and retinal neurodegenerative diseases (RNDs), including open-angle glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Using genome-wide association study data and inverse variance weighting, we found chronotype significantly increased DR risk (OR: 1.60, p = 0.023). Reverse MR showed AMD was inversely associated with short sleep duration and chronotype. Sensitivity analyses supported result robustness. Mediation analysis identified six traits potentially linking chronotype to DR. These findings suggest sleep-related traits may be modifiable risk factors in RNDs, offering insights for early prevention and intervention.},
}
@article {pmid40467849,
year = {2025},
author = {Arend, N},
title = {[Nutritional therapy in ophthalmology-patients' interest and motivation].},
journal = {Die Ophthalmologie},
volume = {122},
number = {9},
pages = {700-707},
pmid = {40467849},
issn = {2731-7218},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Motivation ; *Eye Diseases/diet therapy/epidemiology/psychology ; Aged, 80 and over ; Adult ; *Nutrition Therapy/statistics &amp; numerical data/psychology ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Several therapeutic diets are known for ophthalmologic diseases. Therefore, the present study evaluates the interest of our patients in healthy and therapeutic nutrition.<br><br>METHODS: In all, 100 representative patients answered a&#xa0;structured interview questionnaire about their nutrition behavior and interest in therapeutic diet for their ophthalmologic diseases. Data from our patient files were correlated with their answers.<br><br>RESULTS: Over 70% of the patient were interested in and followed a&#xa0;healthy diet and ate fruits and vegetables daily. Only one third had fish weekly. Two thirds showed high interest in therapeutic diet, especially patients of higher age and with the diagnoses sicca, age related macular degeneration (AMD) and glaucoma. There was no correlation of nutrition interest with the patient sex, disease stage, presence of diabetes or need for intravitreal drug administration. In all, 60% agreed to pay for the consultation, albeit rather low amounts. Greater interest and adherence to a&#xa0;healthy diet but not sex, higher age or stages of disease correlated with the willingness pay.<br><br>CONCLUSION: Our patients who were surveyed had high interest in nutritional therapy for ophthalmologic diseases, and were also theoretically motivated to implement it. Patients with sicca, glaucoma and AMD were more motivated; however this was not related to the stage of their disease. Most patients are willing to only pay small amounts for the consultation.},
}
@article {pmid40467303,
year = {2025},
author = {Michaud, C and Guénot, J and Faurite, C and Gallice, M and Chiquet, C and Vayssière, N and Berry, I and Trotter, Y and Soler, V and Peyrin, C and Cottereau, BR},
title = {Motion Processing in Visual Cortex of Maculopathy Patients.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {45},
number = {30},
pages = {},
pmid = {40467303},
issn = {1529-2401},
mesh = {Humans ; Female ; *Motion Perception/physiology ; *Visual Cortex/physiopathology/blood supply ; Male ; Middle Aged ; *Macular Degeneration/physiopathology/pathology ; Photic Stimulation/methods ; Magnetic Resonance Imaging ; Aged ; Visual Fields/physiology ; Adult ; Scotoma/physiopathology ; Stargardt Disease ; Brain Mapping ; },
abstract = {Previous studies on animal models suggested that visual areas involved in motion processing could undergo important cortical reorganizations following retinal damages. This could have major implications for patients suffering from macular degeneration (MD), one leading cause of vision loss. Here, we performed fMRI recordings in a group of maculopathy patients (N = 7, 3 women, including individuals suffering from age-related macular degeneration or from Stargardt's disease) and a control group to characterize the motion processing cortical network in MD patients and determine whether this network is modified following the onset of the scotoma. We used an experimental protocol based on random-dot kinematograms classically employed to characterize motion-selective areas in the brain. To ensure that the visual information processed by the two groups was equivalent, the visual field in each control participant was masked using an artificial scotoma directly derived from clinical measurements in their paired patient. We found that in MD patients, translational motion elicited significant and robust activations in a restricted cortical network which included the human V5/MT+ complex (hMT+), areas V3A and V6, and a portion of primary visual areas (V1, V2, and V3) connected to peripheral vision. Importantly, the same patterns of responses were also observed in control participants. Moreover, the extent and strength of activation within these motion-selective areas did not differ significantly between the two groups. Altogether, these results suggest that in humans, the motion-selective network does not undergo significant large-scale cortical reorganizations following the onset of MD.},
}
@article {pmid40467021,
year = {2025},
author = {Berni, A and Cheng, Y and Shen, M and El-Mulki, OS and Herrera, G and Beqiri, S and Kastner, JD and Zhang, Q and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Updated Guidelines for Imaging the Choriocapillaris in Eyes with Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Angiography.},
journal = {American journal of ophthalmology},
volume = {278},
number = {},
pages = {52-64},
doi = {10.1016/j.ajo.2025.05.021},
pmid = {40467021},
issn = {1879-1891},
mesh = {Humans ; *Tomography, Optical Coherence/methods/standards ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods ; *Macular Degeneration/physiopathology/diagnosis/diagnostic imaging ; Capillaries/diagnostic imaging/pathology ; *Practice Guidelines as Topic ; Regional Blood Flow/physiology ; Retinal Drusen ; *Retinal Vessels/diagnostic imaging/physiopathology ; },
abstract = {PURPOSE: To update the recommended guidelines when quantifying choriocapillaris (CC) flow deficits (FDs) in eyes with age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>DESIGN: Evidence-based perspective.<br><br>METHODS: Review of literature and experience of authors.<br><br>RESULTS: A current challenge when quantifying CC FDs using SS-OCTA is the implementation of an objective compensation strategy to adjust for the signal attenuation arising under drusen in eyes with AMD. Our previous compensation strategy was used as a general approach to adjust for the OCTA signal attenuation associated with most drusen. However, the variability of the OCTA signal loss under drusen necessitated a more objective strategy that could be tailored to each case. We propose a compensation strategy using a parameter gamma (&#x3b3;) that allows for the selection of an appropriate compensation level. The optimal &#x3b3; value is identified as the one producing the most homogeneous OCT signal across the whole CC structural slab. This approach minimizes the possibility that areas of decreased flow in the compensated CC flow image might reflect drusen-related or compensation-related artifacts rather than true deficits. Additional lesions that present unique challenges when quantifying CC FDs include the presence of choroidal hypotransmission defects (hypoTDs) caused by calcified drusen and hyperreflective foci as well as choroidal hypertransmission defects (hyperTDs) caused by foci of atrophy. We recommend identifying and outlining these regions on an en face sub-retinal pigment epithelium (subRPE) slab with segmentation boundaries between 64 and 400 &#xb5;m beneath the Bruch membrane (BM). The hypoTDs should be excluded from CC quantification because of the lack of significant OCTA signal, whereas the hyperTDs should be excluded from being compensated because doing so can artifactually increase the percentage of CC FDs.<br><br>CONCLUSIONS: The analysis of CC FDs in AMD requires special attention to drusen, hypoTDs, and hyperTDs to avoid introducing artifacts. By properly adjusting the compensation levels under drusen and adjusting the quantification of CC FDs by accounting for hyperTDs and hypoTDs, researchers interested in measuring CC FDs in AMD can have greater confidence in their measurements, particularly when investigating the role of CC flow impairment in AMD progression.},
}
@article {pmid40466938,
year = {2025},
author = {McLellan, FC and Huang, K and Wong, E and Shu, DY},
title = {The Angiofibrotic Switch in Retinal and Choroidal Vascular Diseases: Mechanistic Drivers of Angiogenesis and Endothelial-Mesenchymal Transition.},
journal = {The American journal of pathology},
volume = {195},
number = {8},
pages = {1363-1375},
doi = {10.1016/j.ajpath.2025.05.004},
pmid = {40466938},
issn = {1525-2191},
mesh = {Humans ; *Neovascularization, Pathologic/pathology/metabolism ; Animals ; Fibrosis ; *Choroidal Neovascularization/pathology/metabolism ; *Epithelial-Mesenchymal Transition ; *Retinal Diseases/pathology/metabolism ; Endothelial-Mesenchymal Transition ; Angiogenesis ; },
abstract = {The angiofibrotic switch refers to the pathologic transition from active angiogenesis to fibrosis, a process that contributes to disease progression in retinal and choroidal neovascular diseases, such as age-related macular degeneration and proliferative diabetic retinopathy. This switch marks the replacement of newly formed, fragile blood vessels with fibrotic tissue, ultimately leading to scarring and permanent vision loss. Understanding this process is crucial, as fibrosis results in severe visual impairment and, currently, no anti-fibrotic therapies exist. Central to the angiofibrotic switch is endothelial-mesenchymal transition, a process where endothelial cells lose their vascular endothelial identity and acquire mesenchymal properties, contributing to extracellular matrix deposition and fibrosis. This review explores the cellular and molecular mechanisms underlying the angiofibrotic switch, emphasizing the interplay between angiogenesis, endothelial-mesenchymal transition, and metabolic dysregulation in driving fibrosis. Key mediators, such as transforming growth factor-β and vascular endothelial growth factor, are discussed in the context of their dual roles in promoting angiogenesis and fibrosis. This review underlines the need for early detection methods and targeted therapies to mitigate the angiofibrotic switch and improve outcomes in patients with neovascular retinal and choroidal diseases. By unraveling the complexities of this transition, this review aims to provide a framework for developing innovative diagnostic and therapeutic strategies to prevent fibrosis and mitigate vision loss in retinal and choroidal neovascular diseases.},
}
@article {pmid40466854,
year = {2025},
author = {You, Y and Liu, Y and Huang, L and Lu, WN and Zhang, Y and Nie, T and Jing, M and Hejtmancik, JF and Li, X and Hou, L and Ma, X},
title = {DAPL1 inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells by regulating the TGF-β/MITF pathway.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110473},
pmid = {40466854},
issn = {1096-0007},
support = {Z01 EY000272/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Epithelial-Mesenchymal Transition/physiology ; Mice ; Signal Transduction/physiology ; Mice, Knockout ; *Transforming Growth Factor beta/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; *Adaptor Proteins, Signal Transducing/physiology ; Humans ; Cells, Cultured ; *Gene Expression Regulation/physiology ; *Vitreoretinopathy, Proliferative/metabolism/pathology ; Blotting, Western ; },
abstract = {Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a critical factor in the development of retinopathies, including proliferative vitreoretinopathy (PVR) and age-related macular degeneration (AMD), which are the leading causes of blindness worldwide. Deficiency in DAPL1 can induce RPE-EMT in vivo, and Dapl1 knockout mice (Dapl1 -/-) are prone to PVR, while aged Dapl1 -/- mice display AMD-like pathological features. However, the molecular mechanisms through which DAPL1 regulates RPE-EMT remain largely unknown. Here, using Dapl1 -/- mice and DAPL1 knockdown or overexpression RPE cells, we show that DAPL1 inhibits RPE-EMT by regulating the TGF-β/MITF signaling pathway, a critical signaling pathway/transcription factor in RPE cells. Overexpression of DAPL1 inhibits TGF-β-induced RPE-EMT, while deletion of Dapl1 in mice activates TGF-β signaling, decreases MITF expression, and promotes RPE-EMT under physiological or PVR pathological conditions. Gene therapy demonstrates that transgenic overexpression of MITF in Dapl1 -/- mice inhibits RPE-EMT in vivo and prevents retinal detachment-induced PVR pathological progress, offering hope for future treatment. Similarly, pharmacological therapy with Isoviolanthin, a flavonoid glycoside isolated from traditional medicinal herbs, inhibits TGF-β signaling and increases MITF expression in RPE cells in Dapl1 -/- mice, which then effectively rescues experimental PVR in Dapl1 -/- mice. These results suggest that DAPL1 regulates RPE-EMT at least partial through the TGF-β/MITF pathway and that targeting the TGF-β/MITF pathway could be a potential therapeutic strategy to treat Dapl1 deficiency-induced RPE-EMT-related retinal diseases, instilling hope for the future of retinal disease treatment.},
}
@article {pmid40466770,
year = {2025},
author = {Regillo, C and Kaiser, PK and Kertes, PJ and Gillies, M and Maio-Twofoot, T and D'Souza, D and Guenther, S and Lawrence, D and Holz, FG},
title = {TALON Phase IIIb Study: 32-Week Primary Results of Brolucizumab Using Treat and Extend for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.05.030},
pmid = {40466770},
issn = {2468-6530},
abstract = {OBJECTIVE: To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg using an identical 4-week adjustment treat-and-extend regimen in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Randomized, double-masked, multicenter, active-controlled, 2-arm, phase IIIb study.<br><br>PARTICIPANTS: Patients (N = 737) with untreated, active choroidal neovascularization secondary to nAMD.<br><br>METHODS: Patients were randomized 1:1 to either brolucizumab 6 mg or aflibercept 2 mg with injections at weeks 0, 4, 8, and 16 followed by 4-week interval adjustments depending on disease activity (DA) up to intervals of 16 weeks. After the introduction of the urgent safety measure, patients requiring a 4-week interval were discontinued from study treatment and moved to the standard of care.<br><br>MAIN OUTCOME MEASURES: Coprimary end points were the distribution of the last treatment interval with no DA at week 32 and the average change in best-corrected visual acuity (BCVA) from baseline to weeks 28 and 32. Key secondary end points included average change from baseline in central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), and subretinal pigment epithelium fluid at weeks 28 and 32. Safety end points included the incidence of ocular and nonocular adverse events (AEs) and AEs of special interest (AESIs).<br><br>RESULTS: Brolucizumab achieved superiority to aflibercept in the distribution of last interval with no DA at week 32 (proportion of patients on 12-week treatment intervals: 38.5% vs. 19.8%; 8 weeks: 35.8% vs. 39.9%; 4 weeks: 25.7% vs. 40.2%, respectively; P < 0.0001) and noninferiority to aflibercept for least square mean difference in average change in BCVA from baseline at weeks 28 and 32 (+5.2 vs. +5.1; P < 0.0001). The least square mean difference in the average change in CSFT (&#x3bc;m) from baseline at weeks 28 and 32 (brolucizumab -172.8 vs. aflibercept -142.5) was -30.3 (P = 0.002). Fewer brolucizumab versus aflibercept patients had IRF and/or SRF and subretinal pigment epithelium fluid. Incidences of ocular AEs, serious ocular AEs, and AESIs in the brolucizumab versus aflibercept arms were 29.2% versus 26.1%, 2.5% versus 0.5%, and 5.5% versus 1.1%, respectively.<br><br>CONCLUSIONS: In TALON, more brolucizumab-treated patients achieved longer treatment intervals without DA than aflibercept with comparable visual gains. Brolucizumab showed improved anatomical outcomes and demonstrated an overall favorable benefit/risk profile.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40465138,
year = {2025},
author = {Lai, YA and Tsui, MC and Cheng, SF and Hsieh, YT and Lai, TT and Hsia, Y and Wang, SW and Ma, IH and Hung, KC and Lin, CP and Yang, CH and Yang, CM and Ho, TC},
title = {Early Anatomical and Functional Outcomes of Faricimab in Recalcitrant Neovascular Age-Related Macular Degeneration: A Retrospective Real-World Study in an East-Asian Population.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {8},
pages = {1723-1737},
pmid = {40465138},
issn = {2193-8245},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss, with some eyes showing recalcitrant disease despite standard anti-vascular endothelial growth factor (anti-VEGF) therapy. While clinical trials have demonstrated promising efficacy and safety of faricimab in treatment-naïve patients, only 9% of participants were Asian, and real-world data on its effectiveness in pretreated Asian populations remain limited. This study aims to evaluate the efficacy and longitudinal response of intravitreal faricimab in patients with recalcitrant nAMD in Taiwan by analyzing visual acuity, anatomical outcomes, and treatment interval extension over a 6-month period.<br><br>METHODS: This was a retrospective observational study at National Taiwan University Hospital. Patients switched to intravitreal faricimab (6&#xa0;mg/0.05&#xa0;mL; Vabysmo&#x2122;) from July 2023 to May 2024 with 6&#xa0;months follow-up identified via electronic medical records. Injections were administered without a loading phase. Retreatment was guided by the presence of retinal fluid on optical coherence tomography (OCT), with or without visual decline.<br><br>RESULTS: A total of 33 eyes from 28 patients were analyzed. Visual acuity remained stable over 6&#xa0;months (p&#x2009;=&#x2009;0.147). Central retinal thickness significantly improved from 267 to 235&#xa0;&#x3bc;m at 3&#xa0;months (p&#x2009;=&#x2009;0.002) and remained stable at 6&#xa0;months (p&#x2009;=&#x2009;0.003). Subretinal fluid resolved in 36.4% of eyes at 3&#xa0;months (p&#x2009;<&#x2009;0.001) and 48.5% at 6&#xa0;months (p&#x2009;=&#x2009;0.002), while changes in intraretinal fluid (IRF) and pigment epithelial detachment (PED) height were not significant. Treatment intervals were extended in 52% of eyes, with 56% reaching&#x2009;&#x2265;&#x2009;16 weeks (Q16W) intervals. No serious ocular or systemic adverse events were reported.<br><br>CONCLUSIONS: Intravitreal faricimab demonstrated improved anatomical outcomes with stable visual acuity and extended treatment intervals in patients with recalcitrant nAMD in Taiwan, addressing a key evidence gap. Future studies with longer follow-ups are needed to validate these findings.},
}
@article {pmid40463243,
year = {2025},
author = {Hulleman, JD and Jeon, S and Bali, S and DiCesare, SM and Abbas, A and Daniel, S and Ortega, AJ and Collier, GE and Yang, J and Bhattacharyaa, A and McCoy, MK and Joachimiak, LA and Posner, BA},
title = {Select azo compounds post-translationally modulate HTRA1 abundance and activity potentially through interactions at the trimer interface.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40463243},
issn = {2692-8205},
support = {P30 EY030413/EY/NEI NIH HHS/United States ; R21 EY032693/EY/NEI NIH HHS/United States ; RF1 AG076459/AG/NIA NIH HHS/United States ; T35 EY026510/EY/NEI NIH HHS/United States ; },
abstract = {High-temperature requirement protein A1 (HTRA1) is a secreted serine protease with diverse substrates, including extracellular matrix proteins, proteins involved in amyloid deposition, and growth factors. Accordingly, HTRA1 has been implicated in a variety of neurodegenerative diseases including a leading cause of blindness in the elderly, age-related macular degeneration (AMD). In fact, genome wide association studies have identified that the 10q26 locus which contains HTRA1 confers the strongest genetic risk factor for AMD. A recent study has suggested that AMD-associated risk alleles in HTRA1 correlate with a significant age-related defect in HTRA1 synthesis in the retinal pigmented epithelium (RPE) within the eye, possibly accounting for AMD susceptibility. Thus, we sought to identify small molecule enhancers of HTRA1 transcription and/or protein abundance using an unbiased high-throughput screening approach. To accomplish this goal, we used CRISPR/Sp.Cas9 engineering to introduce an 11 amino acid luminescent peptide tag (HiBiT) onto the C-terminus of HTRA1 in immortalized ARPE-19 cells. Editing was very efficient (~88%), verified by genomic DNA analysis, short interfering RNA (siRNA), and HiBiT blotting. Nineteen-hundred and twenty compounds from two libraries were screened. An azo compound with reported anti-amyloidogenic and cardioprotective activity, Chicago Sky Blue 6B (CSB), was identified as an enhancer of endogenous HTRA1 secretion (2.0 ± 0.3 fold) and intracellular levels (1.7 ± 0.2 fold). These results were counter-screened using HiBiT complement factor H (CFH) edited ARPE-19 cells, verified using HiBiT blotting, and were not due to HTRA1 transcriptional changes. Importantly, serine hydrolase activity-based protein profiling (SH-ABPP) demonstrated that CSB does not affect HTRA1's specific activity. However, interestingly, in follow-up studies, Congo Red, another azo compound structurally similar to CSB, also substantially increased intracellular HTRA1 levels (up to 3.6 ± 0.3 fold) but was found to significantly impair HTRA1 enzymatic reactivity (0.45 ± 0.07 fold). Computational modeling of potential azo dye interaction with HTRA1 suggests that CSB and Congo Red can bind to the non-catalytic face of the trimer interface but with different orientation tolerances and interaction energies. These studies identify select azo dyes as HTRA1 chemical probes which may serve as starting points for future HTRA1-centered small molecule therapeutics.},
}
@article {pmid40458667,
year = {2025},
author = {Heier, JS and Holekamp, NM and Busquets, MA and Elman, MJ and Schechet, SA and Ladd, BS and Kapoor, KG and Schneider, EW and Leung, EH and Danis, RP and Nahen, K and Mohan, N and Benyamini, G},
title = {Pivotal Trial Validating Usability and Visualization Performance of Home OCT in Neovascular Age-Related Macular Degeneration: Report 1.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100772},
pmid = {40458667},
issn = {2666-9145},
abstract = {PURPOSE: To validate the usability and visualization performance of the index test of the home OCT system (HOCT) during a pivotal study toward de novo US Food and Drug Administration marketing authorization.<br><br>DESIGN: A prospective, 5-week longitudinal, at-home visualization multicenter study with preplanned office visits at week 1 and week 5 and as-needed interim visits.<br><br>PARTICIPANTS: The study enrolled adults aged &#x2265;55 years diagnosed with neovascular age-related macular degeneration (nAMD) on anti-VEGF therapy in at least 1 eligible eye and best-corrected visual acuity of 20/320 or better.<br><br>METHODS: Participants self-installed and imaged daily with the HOCT at home for 5 weeks with 2 or 3 interspersed office visits at 1 and 5 weeks with interim reading center (RC)-triggered visits including a comparator in-office OCT (IO-OCT). Scans with an acceptable quality signal index were independently graded by the RC in a masked manner.<br><br>MAIN OUTCOME MEASURES: Ability to self-image at home, positive and negative percent agreement (NPA) in visualization of total hyporeflective spaces (TRO) on HOCT and on IO-OCT.<br><br>RESULTS: At home, self-imaging success rate was 96.1% (95% confidence interval [CI]: 92.2%-98.4%). One hundred eighty participants self-imaged the primary and secondary eyes 5426 and 4012 times with a mean (standard deviation) manufacturer signal quality index of 4.40 (1.26) and 4.58 (1.28), respectively. Positive percent agreement was 86.6% (95% CI: 80.4%-92.8%) and NPA was 86.1% (95% CI: 80.4%-91.8%), with nearly all disagreements being minimal.<br><br>CONCLUSIONS: The target population successfully self-installed and self-imaged at home with image quality comparable to IO-OCT. The findings of the visualization study support the intended use of the system as a tool to monitor TRO at home between routine clinical visits during the management of nAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40456958,
year = {2025},
author = {Veritti, D and Sarao, V and Lanzetta, P},
title = {Extended duration of VEGF inhibition with aflibercept 8 mg: the role of reduced ocular clearance.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {10},
pages = {2985-2987},
pmid = {40456958},
issn = {1435-702X},
}
@article {pmid40456126,
year = {2025},
author = {Lee, HJ and Lee, EK and Sagong, M and Woo, SJ and Park, KH and Park, UC},
title = {CLINICAL CHARACTERIZATION AND TREATMENT OUTCOMES OF MACULAR NEOVASCULARIZATION IN RETINITIS PIGMENTOSA.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {10},
pages = {1951-1958},
doi = {10.1097/IAE.0000000000004541},
pmid = {40456126},
issn = {1539-2864},
mesh = {Humans ; *Retinitis Pigmentosa/complications/drug therapy/diagnosis ; Middle Aged ; Male ; Retrospective Studies ; Aged ; Female ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Visual Acuity/physiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Fluorescein Angiography ; Treatment Outcome ; Ranibizumab/therapeutic use ; Electroretinography ; *Retinal Neovascularization/drug therapy/diagnosis/etiology/epidemiology ; Follow-Up Studies ; *Macula Lutea/pathology ; Republic of Korea/epidemiology ; Bevacizumab ; },
abstract = {PURPOSE: To investigate the clinical features, prevalence, and treatment outcomes of macular neovascularization (MNV) in patients with retinitis pigmentosa (RP).<br><br>METHODS: The authors retrospectively reviewed the medical records of patients diagnosed with RP at three tertiary hospitals in South Korea. The diagnosis of RP was based on symptoms, funduscopic findings, and electroretinography. All patients were treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) injection.<br><br>RESULTS: Among the 2,730 patients with RP, MNV was identified in 7 patients (prevalence: 0.26%). The median age at MNV onset was 59 years (range: 52-75 years). The median number of anti-VEGF injections was 5 (range: 1-43). After treatment, visual and anatomical improvements were observed in all patients. In six patients, MNV stabilized without recurrence after one to six anti-VEGF injections, whereas one patient needed repeated treatment. The 5 patients with a follow-up period more than 3 years exhibited no signs of disease progression or further constriction of the visual field.<br><br>CONCLUSION: The MNV is a rare complication in patients with RP, occurring at a younger age than in those with age-related macular degeneration. Intravitreal anti-VEGF injections for the treatment of RP-related MNV were effective in preserving vision without accelerating the clinical course of RP.},
}
@article {pmid40455475,
year = {2025},
author = {Zitser, M},
title = {Painting Through Macular Degeneration.},
journal = {AMA journal of ethics},
volume = {27},
number = {6},
pages = {E438-439},
doi = {10.1001/amajethics.2025.438},
pmid = {40455475},
issn = {2376-6980},
mesh = {Humans ; *Macular Degeneration/psychology ; *Narration ; *Paintings ; },
abstract = {This article investigates the importance of storytelling for human well-being. Special attention is given to the roles storytelling has played in human evolution, how sharing stories informs embodied experiences, and the role of storytelling within medicine to promote health.},
}
@article {pmid40455044,
year = {2025},
author = {Klaassen, I and Vader, MJC and Aissa, K and Tanck, MWT and Schlingemann, RO and , },
title = {Several Common Genetic Variations Associate With Functional or Anatomic Effects of Anti-VEGF Treatment in Conditions With Macular Edema.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {6},
pages = {2},
pmid = {40455044},
issn = {1552-5783},
mesh = {Humans ; *Macular Edema/drug therapy/genetics/physiopathology ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/therapeutic use ; Genome-Wide Association Study ; *Polymorphism, Single Nucleotide ; *Bevacizumab/therapeutic use ; Visual Acuity/physiology ; Intravitreal Injections ; Male ; Female ; Tomography, Optical Coherence ; Retinal Vein Occlusion/drug therapy/genetics ; Aged ; Diabetic Retinopathy/drug therapy/genetics ; },
abstract = {PURPOSE: This study aimed to identify genetic factors that may influence the effectiveness of anti-vascular endothelial growth factor (VEGF) treatment for macular edema (ME).<br><br>METHODS: We performed a genome-wide association study (GWAS) on 606 patients with macular edema that were treated with bevacizumab or ranibizumab from three randomized clinical trials, using a Infinium Global Screening Array. Well-characterized patient groups included diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), with changes in best-corrected visual acuity (BCVA) and anatomical changes in central subfield thickness (CST) as outcomes. We conducted a meta-analysis on the combined patient groups, a targeted analysis on 28 previously reported genetic variants related to anti-VEGF response, and on variants of six genes involved in ME pathophysiology.<br><br>RESULTS: GWAS meta-analysis identified 12 SNPs (P < 1 &#xd7; 10-6), of which three SNPs reached genome-wide significance (P < 5 &#xd7; 10-8) and were linked to changes in CST after 6 months of anti-VEGF treatment. In addition, a genomic locus in the SGCZ gene was linked to changes in BCVA. Targeted GWAS revealed significant associations between changes in BCVA and variants in KDR, IL6, NRP1, and SPNS2, all known for their roles in VEGF signaling and retinal vascular permeability. Furthermore, changes in CST were associated with PLVAP, an important gene in vascular hyperpermeability in ME.<br><br>CONCLUSIONS: This GWAS meta-analysis uncovered genetic variants potentially linked to responses to anti-VEGF treatment in patients with retinal conditions featuring vascular leakage and/or ME. These findings could aid in identifying genetic markers for treatment response prediction or uncover new pathways relevant to retinal vascular leakage and ME.},
}
@article {pmid40455036,
year = {2025},
author = {Jayananthan, V and Taylor, TH and Greentree, DH and Collison, B and Kerur, N},
title = {AI Quantification of Vascular Lesions in Mouse Fundus Fluorescein Angiography.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {6},
pages = {4},
pmid = {40455036},
issn = {2164-2591},
support = {P30 EY032857/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Fluorescein Angiography/methods ; Mice ; *Artificial Intelligence ; Fundus Oculi ; Mice, Knockout ; *Choroidal Neovascularization/diagnostic imaging ; Disease Models, Animal ; *Retinal Vessels/pathology/diagnostic imaging ; *Retinal Neovascularization/diagnostic imaging ; Image Processing, Computer-Assisted/methods ; },
abstract = {PURPOSE: Quantifying vascular leakage in fundus fluorescein angiography (FFA) is a critical endpoint in preclinical models of diseases such as neovascular age-related macular degeneration, retinopathy of prematurity, and diabetic retinopathy. Traditional manual methods are labor intensive and prone to variability. We developed an artificial intelligence (AI)-assisted method to improve efficiency and accuracy in quantifying vascular lesions in FFA images.<br><br>METHODS: Nikon NIS-Elements software with AI functionality was used to create an automated FFA analysis method. FFA images were acquired using the Phoenix MICRON IV imaging system in two mouse models of ocular angiogenesis: (1) very low-density lipoprotein receptor (Vldlr) knockout mice exhibiting spontaneous pathological chorioretinal neovascularization, and (2) a laser-induced choroidal neovascularization model. The AI model was trained on manually segmented FFA images to delineate lesions and quantify lesion area and fluorescence intensity.<br><br>RESULTS: The AI model demonstrated high accuracy in quantifying vascular lesions in FFA images, achieving 99.7% agreement with manual counts. It attained a precision, recall, and F1 score of 0.94, with an intraclass correlation coefficient (ICC) of 0.991. The model showed strong spatial agreement with manual segmentations and consistent lesion area measurements. On validation images, it maintained expert-level performance (ICC = 0.998) with high sensitivity and precision. Additionally, it effectively captured temporal changes in vascular leakage by measuring lesion area and fluorescence intensity, demonstrating robustness in real-world experiments.<br><br>CONCLUSIONS: Our AI model quantifies vascular lesions in FFA images with high accuracy, outperforming manual analysis.<br><br>TRANSLATIONAL RELEVANCE: AI-based quantification provides a scalable, consistent alternative to manual methods, enhancing research efficiency.},
}
@article {pmid40454673,
year = {2025},
author = {Taylor, LJ and Josan, AS and MacLaren, RE},
title = {Exploring standard and low luminance visual acuity and the Moorfields Acuity Chart as outcome measures in inherited retinal disease.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {5},
pages = {1158-1163},
pmid = {40454673},
issn = {1475-1313},
support = {NIHR202821//Research for Patient Benefit Programme/ ; //NIHR Oxford Biomedical Research Centre/ ; },
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; *Vision Tests/methods/instrumentation ; Middle Aged ; Adult ; Aged ; Reproducibility of Results ; *Retinal Diseases/physiopathology/diagnosis/genetics ; Young Adult ; },
abstract = {INTRODUCTION: Standard visual acuity (VA) is often insensitive to subtle changes in vision that result from inherited retinal disease. Low luminance VA (LLVA) has grown in popularity as an alternative acuity measure. A new test, the Moorfields Acuity Chart (MAC) has been designed as a more sensitive and repeatable test for use in patients with age-related macular degeneration. The study explores the utility and repeatability of standard VA, LLVA and the MAC in a mixed cohort of patients with inherited retinal disease.<br><br>METHODS: Participants were recruited as part of the visual function in retinal degeneration study (Ethics Reference 20/WM/0283). Standard VA was obtained using the Early Treatment of Diabetic Retinopathy study (ETDRS) chart placed at 4&#x2009;m. LLVA was obtained using the same ETDRS chart with the addition of a 2.0-log unit neutral density filter. MAC VA was obtained using standard clinic room lighting. All participants completed repeated testing.<br><br>RESULTS: Thirty-five patient participants and 36 healthy controls, with logMAR 1.00 (6/60) or better, completed testing. Both LLVA and MAC VA were reduced compared to standard VA in patient participants and healthy controls (linear mixed model: p&#x2009;<&#x2009;0.001). All three acuity tests show comparable sensitivity, specificity and repeatability. A subset of participants (patient participants n&#x2009;=&#x2009;34, healthy controls n&#x2009;=&#x2009;35) completed microperimetry. Post hoc analysis of microperimetry volume sensitivity correlated significantly with all of the acuity tests and showed no significant difference in the gradient of the slopes. This suggests that VA, LLVA and MAC VA decline at a consistent rate with disease progression.<br><br>CONCLUSION: All three acuity tests could be considered viable outcome measures for clinical trials. For patients with early to moderate inherited retinal disease (logMAR 1.00 (6/60) or better), no single acuity chart appeared significantly beneficial.},
}
@article {pmid40453785,
year = {2025},
author = {Kazemzadeh, K},
title = {Artificial intelligence in ophthalmology: opportunities, challenges, and ethical considerations.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {14},
number = {1},
pages = {255-272},
pmid = {40453785},
issn = {2322-3219},
abstract = {BACKGROUND: By leveraging the imaging-rich nature of ophthalmology and optometry, artificial intelligence (AI) is rapidly transforming the vision sciences and addressing the global burden of ocular diseases. The ability of AI to analyze complex imaging and clinical data allows unprecedented improvements in diagnosis, management, and patient outcomes. In this narrative review, we explore the current and emerging opportunities of utilizing AI in the vision sciences, critically examine the associated challenges, and discuss the ethical implications of integrating AI into clinical practice.<br><br>METHODS: We searched PubMed/MEDLINE and Google Scholar for English-language articles published from January 1, 2005, to March 31, 2025. Studies on AI applications in ophthalmology and optometry, focusing on diagnostic performance, clinical integration, and ethical considerations, were included, irrespective of study design (clinical trials, observational studies, validation studies, systematic reviews, and meta-analyses). Articles not related to the use of AI in vision care were excluded.<br><br>RESULTS: AI has achieved high diagnostic accuracy across different ocular domains. In terms of the cornea and anterior segment, AI models have detected keratoconus with sensitivity and accuracy exceeding 98% and 99.6%, respectively, including in subclinical cases, by analyzing Scheimpflug tomography and corneal biomechanics. For cataract surgery, machine learning-based intraocular lens power calculation formulas, such as the Kane and ZEISS AI formulas, reduce refractive errors, achieving mean absolute errors below 0.30 diopters and performing particularly well in highly myopic eyes. AI-based retinal screening systems, such as the EyeArt and IDx-DR, can autonomously detect diabetic retinopathy with sensitivities above 95%, while deep learning models can predict age-related macular degeneration progression with an area under the receiver operating characteristic curve exceeding 0.90. In glaucoma detection, fundus and optical coherence tomography-based AI models have reached pooled sensitivity and specificity exceeding 90%, although performance varies with disease stage and population diversity. AI has also advanced strabismus detection, amblyopia risk prediction, and myopia progression forecasting by using facial analysis and biometric data. Currently, key challenges in implementing AI in ophthalmology include dataset bias, limited external validation, regulatory hurdles, and ethical issues, such as transparency and equitable access.<br><br>CONCLUSIONS: AI is rapidly transforming vision sciences by improving diagnostic accuracy, streamlining clinical workflow, and broadening access to quality eye care, particularly in underserved regions. Its integration into ophthalmology and optometry thus holds significant promise for enhancing patient outcomes and optimizing healthcare delivery. However, to harness the transformative potential of AI fully, sustained multidisciplinary collaboration, involving clinicians, data scientists, ethicists, and policymakers, is essential. Rigorous validation processes, transparency in algorithm development, and strong ethical oversight are equally important to mitigate risks such as bias, data misuse, and unequal access. Responsible implementation of AI in the vision sciences is essential to ensure that all populations are served equitably.},
}
@article {pmid40451848,
year = {2025},
author = {Hara, H},
title = {Research Progress in Drug Development Based on Functional Molecules Involved in Pathogenesis and Analysis of Their Mechanisms.},
journal = {Biological &amp; pharmaceutical bulletin},
volume = {48},
number = {6},
pages = {744-758},
doi = {10.1248/bpb.b25-00069},
pmid = {40451848},
issn = {1347-5215},
mesh = {Animals ; Humans ; *Drug Development ; *Glaucoma/drug therapy/pathology ; *Macular Degeneration/drug therapy ; Disease Models, Animal ; Mice ; Diabetic Retinopathy/drug therapy ; },
abstract = {Ocular diseases that result in blindness impair the QOL of patients as well as cause significant socioeconomic losses. Glaucoma is the leading cause of blindness, followed by retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration (AMD). Although the pathogeneses of these ocular diseases differ, they are all retinal diseases that lead to blindness owing to progressive retinal damage. However, the mechanisms underlying the pathogenesis and progression of these diseases have not yet been fully elucidated. In addition, treatment methods for these diseases have not yet been fully established, and their pathophysiology should be elucidated to establish novel treatment methods and drugs. Rodent pathological models, particularly mice and rats, have been established to elucidate the pathogenesis of these diseases. However, anatomical differences between the eyes of humans and rodents suggest that differences in pathogenic mechanisms may exist. In addition, species differences in drug responsiveness have become an issue in various respects, making it increasingly difficult to directly extrapolate the results obtained in rodents to humans. Therefore, evaluations using non-human primates, which are physiologically similar to humans, are required. This review outlines the basic research of AMD and glaucoma models using mice and non-human primates and their therapeutic strategies, focusing on the research findings.},
}
@article {pmid40451555,
year = {2025},
author = {Liu, J and Hu, J and Li, Y and Hu, N and Wang, Y and Chang, B and Guo, Y and Li, X and Zhang, Q and Ming, Y and Lin, C and Ji, H and Yang, Z and Tang, J},
title = {Microneedle-mediated biomimetic nanoparticles for targeted antioxidant and anti-inflammatory therapy in age-related macular degeneration.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {384},
number = {},
pages = {113908},
doi = {10.1016/j.jconrel.2025.113908},
pmid = {40451555},
issn = {1873-4995},
mesh = {Animals ; Rabbits ; *Macular Degeneration/drug therapy/pathology ; *Antioxidants/administration &amp; dosage/therapeutic use ; *Nanoparticles/administration &amp; dosage/chemistry ; *Anti-Inflammatory Agents/administration &amp; dosage/therapeutic use ; Humans ; *Drug Delivery Systems ; *Resveratrol/administration &amp; dosage/therapeutic use ; Needles ; Retinal Pigment Epithelium/metabolism ; *Biomimetic Materials/administration &amp; dosage/chemistry ; Oxidative Stress/drug effects ; Iodates ; Biomimetics ; Retina/drug effects ; },
abstract = {Age-related macular degeneration (AMD) remains the leading cause of vision loss worldwide, with the lack of effective treatment for dry AMD posing a significant clinical challenge. Current therapies for wet AMD, while effective, are invasive, costly, and associated with notable side effects. Dry AMD, which is characterized by progressive retinal damage driven by oxidative stress and inflammation, lacks targeted therapeutic options, underscoring the critical need for innovative intervention strategies. Here, we present a dissolving microneedle-based delivery platform incorporating retinal pigment epithelial (RPE) cell membrane-cloaked biomimetic nanoparticles loaded with resveratrol. This system is designed for minimally invasive, targeted drug delivery to the retina. Upon administration, the microneedles rapidly dissolve, enabling localized release of the nanoparticles. The RPE membrane coating provides homologous targeting, enhancing cellular uptake while mitigating systemic exposure. In a rabbit model of NaIO3-induced dry AMD, this approach demonstrated significant preservation of retinal architecture, including significant mitigation of oxidative stress, inflammation, and retinal degeneration, alongside excellent safety and biocompatibility profiles. This innovative delivery strategy addresses the critical barriers in AMD treatment by offering a safe, efficient, and patient-friendly solution, paving the way for its broader application in posterior eye diseases.},
}
@article {pmid40451292,
year = {2025},
author = {Hafner, M and Asani, B and Eckardt, F and Liesenhoff, C and Kufner, A and Siedlecki, J and Schworm, B and Priglinger, S and Schiefelbein, JB},
title = {Deep learning-assisted analysis of biomarker changes after increase of dosing from aflibercept 2 mg to 8 mg in therapy-resistant neovascular age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40451292},
issn = {2397-3269},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Female ; Male ; Aged ; Intravitreal Injections ; *Deep Learning ; Biomarkers/metabolism ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Visual Acuity ; Follow-Up Studies ; Dose-Response Relationship, Drug ; Treatment Outcome ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Middle Aged ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries. There are many different intravitreal anti-vascular endothelial growth factor (VEGF) drugs available for the treatment of neovascular AMD (nAMD). Unfortunately, not all patients respond equally well to the drugs, and some show recurrences during treatment. Since 01/2024, aflibercept 8 mg represents an additional treatment option and contains a four times higher dosage than the already known aflibercept 2 mg.<br><br>METHODS: To evaluate the real-world efficacy of aflibercept 8&#x2009;mg in refractory nAMD patients, focusing on changes in key optical coherence tomography biomarkers over a follow-up period of the first four aflibercept 8&#x2009;mg injections using a deep learning-based semantic segmentation algorithm. Inclusion criteria were: switch to aflibercept 8&#x2009;mg after insufficient response to aflibercept 2&#x2009;mg, marked by persistent retinal fluid or inability to extend treatment beyond 6&#x2009;weeks; completion of at least 3&#x2009;months (90 days) follow-up under treat-and-extend treatment regime; and no confounding conditions like intraocular infection, uveitis or other retinal diseases.<br><br>RESULTS: 23 eyes of 21 patients with therapy-resistant nAMD were switched to aflibercept 8&#x2009;mg. All patients had previously received aflibercept 2&#x2009;mg, with an average of 30.7 previous anti-VEGF injections. Significant reductions in intraretinal fluid and fibrovascular pigment epithelial detachment at timepoint V3 were observed. The decrease in subretinal fluid and central retinal thickness at V3 was not significant. Treatment intervals extended significantly by 24%, from a baseline average of 34 days to 42 days. Best-corrected visual acuity remained stable throughout the study period.<br><br>CONCLUSIONS: Aflibercept 8&#x2009;mg demonstrated significant efficacy and durability in reducing nAMD biomarkers and extending intervals in a real-world setting. The use of deep learning for biomarker quantification highlighted its potential for enhancing treatment monitoring and decision-making. Future studies with a larger patient cohort and prospective study setting should explore long-term outcomes and integration of artificial intelligence-driven analysis.},
}
@article {pmid40451259,
year = {2025},
author = {Starr, MR and Lovett, EA and Israilevich, R and Hsu, J and Hua, P and Huang, J and Maguire, MG and Martin, DF and Ying, GS and Kuriyan, AE},
title = {Association of changes in optical coherence tomography metrics with changes in refractive error in patients with neovascular age-related macular degeneration in the CATT.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {6},
pages = {e898-e905},
doi = {10.1016/j.jcjo.2025.05.016},
pmid = {40451259},
issn = {1715-3360},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology/complications ; Female ; Male ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; *Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; *Refraction, Ocular/physiology ; Follow-Up Studies ; *Refractive Errors/physiopathology/diagnosis ; Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; Aged, 80 and over ; },
abstract = {OBJECTIVE: Assess the change in refractive error (RE) in patients receiving anti-vascular endothelial growth factor (VEGF) therapy for exudative age-related macular degeneration.<br><br>METHODS: Post hoc analysis of data from the Comparison of AMD Treatments Trials (CATT). Associations between spherical equivalent (SphE) change and optical coherence tomography (OCT) metrics were evaluated using correlation coefficients (r) and regression analyses stratified by baseline lens status.<br><br>RESULTS: Analysis included 1 171 patients with OCT fluid in the study eye at baseline. The mean (&#xb1; SD) of SphE shifted toward myopia in study eyes from 0.62 &#xb1; 1.63 diopters (D) at baseline to 0.50 &#xb1; 1.61 D at 2 years (p < 0.0001). Phakic study eyes had larger myopic shifts than pseudophakic eyes at 2 years (-0.19 &#xb1; 0.97 D vs -0.06 &#xb1; 0.90 D; p&#x202f;=&#x202f;0.03). In phakic study eyes, the RE change was significantly correlated with change in subretinal thickness (Spearman r&#x202f;=&#x202f;0.21; p < 0.0001), subretinal tissue complex (r&#x202f;=&#x202f;0.12; p&#x202f;=&#x202f;0.01), and total thickness (r&#x202f;=&#x202f;0.36; p < 0.0001). A myopic shift greater than 1.0 D occurred in 74 (7.0%) and 104 (10.2%) study eyes at years 1 and 2, respectively.<br><br>CONCLUSION: Among CATT participants, the RE of study eyes shifted toward myopia at 2 years with phakic eyes having larger shifts. OCT metric changes were weakly correlated with changes in RE, suggesting that drying of the macula with anti-VEGF therapy may have a minor impact on RE. Still, 10% of patients may develop a 1 D myopic shift at 2 years, typically in those with more baseline fluid. Patients with neovascular AMD may be able to update their spectacles, even if macular edema is present, as the change in RE is negligible when drying the macula.},
}
@article {pmid40451257,
year = {2025},
author = {Schweighofer, J and Birner, K and Mohamed, H and Schrittwieser, J and Bogunovic, H and Reiter, GS and Schmidt-Erfurth, U},
title = {Benchmarking test-retest variability in microperimetry for intermediate age-related macular degeneration using MP-3 and MAIA.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {6},
pages = {e879-e887},
doi = {10.1016/j.jcjo.2025.05.002},
pmid = {40451257},
issn = {1715-3360},
mesh = {Humans ; *Visual Field Tests/instrumentation/standards/methods ; Cross-Sectional Studies ; Prospective Studies ; Male ; Female ; Aged ; Tomography, Optical Coherence/methods ; Reproducibility of Results ; *Visual Fields/physiology ; *Visual Acuity ; *Benchmarking/methods ; *Macular Degeneration/diagnosis/physiopathology ; Aged, 80 and over ; Middle Aged ; },
abstract = {OBJECTIVE: Microperimetry (MP) has emerged as a clinical functional endpoint in nonexudative age-related macular degeneration (AMD). In this study, we aim to provide reference values for test-retest outcomes on two MP devices in intermediate AMD (iAMD).<br><br>DESIGN: Prospective, cross-sectional study.<br><br>PARTICIPANTS: 3 600 stimuli from 20 eyes in 20 subjects.<br><br>METHODS: Patients diagnosed with iAMD underwent consecutive testing on MP-3 (NIKED, Gamagori, Japan) and MAIA (CenterVue Icare, Padova, Italy). The obtained point-wise sensitivity (PWS) measurements were superimposed with optical coherence tomography (OCT) (Spectralis, Heildelberg Engineering) acquired. Hyperreflective foci (HRF), drusen volume, ellipsoid zone (EZ)-thickness and outer nuclear layer (ONL)-thickness were quantified with deep-learning algorithms. Subretinal drusenoid deposits (SDD) were manually annotated. We assessed test-retest repeatability at the location of these biomarkers using Bland-Altmann coefficients of repeatability. Furthermore, interdevice correlation, fixation stabilities, and examination durations were evaluated.<br><br>RESULTS: Comparable overall point-wise retest variances were detected for MP-3 (&#xb1;4.54 dB) and MAIA (&#xb1;5.24 dB). SDDs led to significantly worse repeatability in the MAIA device (p&#x202f;=&#x202f;0.03). Drusen, HRF, EZ-thickness, and ONL thickness had no significant impact on test-retest variance. A good intradevice correlation (MP-3: 0.869 [0.851 - 0.886] MAIA 0.848 [0.827 - 0.867]), and a good mean interdevice correlation (0.841 [0.819 - 0.861]) was observed.<br><br>CONCLUSIONS: Intradevice and interdevice repeatability for MP examinations with MP-3 and MAIA in patients with iAMD can be considered as good. Biomarkers except for SDD show no significant impact in repeatability in both devices. This supports MP as a reliable functional endpoint in clinical trials in iAMD.},
}
@article {pmid40450331,
year = {2025},
author = {Huang, Z and Liu, S and Chen, C and Zhang, K and Du, Y and Zhu, X},
title = {Optimizing serum 25(OH)D levels to mitigate the risk of age-related ocular diseases: insights from a large-scale prospective cohort study.},
journal = {Nutrition journal},
volume = {24},
number = {1},
pages = {88},
pmid = {40450331},
issn = {1475-2891},
support = {82122017, 82271069, 81870642, 82371040, 81970780, 81470613, 81670835 and 82201161//the National Natural Science Foundation of China/ ; 23Y11909800 and 21S31904900//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; SHDC12020111//Clinical Research Plan of Shanghai Shenkang Hospital Development Center/ ; shslczdzk01901//Shanghai Municipal Key Clinical Specialty Program/ ; },
mesh = {Humans ; *Vitamin D/blood/analogs &amp; derivatives ; Female ; Male ; Prospective Studies ; Aged ; Middle Aged ; *Eye Diseases/blood/epidemiology/prevention &amp; control ; Risk Factors ; Macular Degeneration/epidemiology/blood/prevention &amp; control ; Cataract/epidemiology/blood/prevention &amp; control ; United Kingdom/epidemiology ; Glaucoma, Open-Angle/epidemiology/blood/prevention &amp; control ; Proportional Hazards Models ; Diabetic Retinopathy/epidemiology/blood/prevention &amp; control ; Incidence ; },
abstract = {BACKGROUND: Investigations into the association between serum 25-hydroxyvitamin D (25(OH)D) levels and the risk of age-related ocular diseases have yielded inconsistent results. Thus, we aimed to provide robust longitudinal evidence, identify optimal serum thresholds, and explore the underlying mechanisms.<br><br>METHODS: We analyzed data of 322,953 participants from the UK Biobank. The serum 25(OH)D levels were assessed using chemiluminescent immunoassay. Outcomes were incidences of cataract, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. Nonlinear relationships were explored using restricted cubic splines, and mediation analyses were performed to delineate potential mechanistic pathways.<br><br>RESULTS: Our findings revealed U-shaped associations for cataract and AMD, and L-shaped associations for DR (all P&#x2009;<&#x2009;0.05), with an optimal threshold of approximately 50 nmol/L, while no association with POAG was observed. Below this threshold, each 10 nmol/L increase in serum 25(OH)D concentration was linked to a 3.5%, 4.2%, and 6.0% reduction in the risk of cataract, AMD, and DR, respectively (HR 0.965 [95% CI 0.951-0.980]; HR 0.958 [95% CI 0.921-0.997]; HR 0.940 [95% CI 0.894-0.989], respectively), while above 50 nmol/L, no significant protective effects were observed. Mediation analyses revealed that the low-grade inflammation score and triglyceride-glucose index may mediate the effects of serum 25(OH)D on cataract and DR.<br><br>CONCLUSIONS: This study identified 50 nmol/L as the optimal serum 25(OH)D threshold for reducing risks of cataract, AMD and DR, with no benefits beyond this level. The protective effects may be mediated through modulation of inflammation and glucolipid metabolism pathways. The threshold effects highlight the importance of targeted vitamin D supplementation under careful monitoring of serum levels to optimize ocular health outcomes.},
}
@article {pmid40449688,
year = {2025},
author = {Eo, H and Park, J and Ju, IG and Oh, MS},
title = {6-shogaol, a bioactive component of ginger, alleviates aging-induced ocular inflammation and ER stress in the 25-month-old mice.},
journal = {The Journal of nutritional biochemistry},
volume = {144},
number = {},
pages = {109980},
doi = {10.1016/j.jnutbio.2025.109980},
pmid = {40449688},
issn = {1873-4847},
mesh = {Animals ; *Endoplasmic Reticulum Stress/drug effects ; Mice, Inbred C57BL ; *Zingiber officinale/chemistry ; *Catechols/pharmacology ; *Aging ; Male ; *Macular Degeneration/drug therapy/pathology ; Mice ; Retina/drug effects/pathology/metabolism ; Inflammation/drug therapy ; },
abstract = {In the elderly population, age-related macular degeneration (AMD) is a major cause of visual impairment, characterized by a thinner retinal pigment epithelium and loss of photoreceptors. 6-shogaol (6S), a component of dried Zingiber officinale Roscoe, has been studied for its multiple therapeutic effects. The current study aimed to investigate the effect of 6S supplementation on AMD. 25-month-old C57BL/6 mice were orally administered with 10 mg/kg of 6S for 28 consecutive days. The thickness of the retinal layer was measured by histological analysis. mRNA expression related to fibrosis, inflammation and endoplasmic reticulum stress was measured by real-time polymerase chain reaction. As a result, 6S increased the thickness of the retinal layer and promoted postsynaptic density protein-95 expression in the outer plexiform layer of the aged mice. Moreover, 6S suppressed ocular mRNA expression related to the fibrotic process, including transforming growth factor beta, collagen type 1 alpha 1, and alpha smooth muscle actin. Furthermore, 6S reduced pro-inflammatory cytokines including tumor necrosis factor alpha, interleukin 1 beta, cyclooxygenase-2, and inducible nitric oxide synthase in the eyeballs of aged mice. Lastly, 6S inhibited ocular endoplasmic reticulum stress measured by mRNA expression of C/EBP homologous protein and spliced X-box binding protein-1 in the aged mice. Taken together, these findings suggest that 6S and dried ginger could be a potential nutraceutical candidate for AMD or other age-related eye diseases.},
}
@article {pmid40449644,
year = {2025},
author = {Chiang, A and Davis, M and Stevens, W and Garg, S and Sheidow, T and Jones, DL and Intorcia, M and McKeown, A and Schmidt-Erfurth, UM and Sarda, SP and Baumal, CR},
title = {Visual Acuity and Quality of Life Outcomes With Pegcetacoplan Treatment: A Post Hoc Analysis From the OAKS and DERBY Trials.},
journal = {American journal of ophthalmology},
volume = {277},
number = {},
pages = {471-481},
doi = {10.1016/j.ajo.2025.05.023},
pmid = {40449644},
issn = {1879-1891},
mesh = {Humans ; *Visual Acuity/physiology ; *Quality of Life ; Male ; Female ; Double-Blind Method ; Aged ; *Geographic Atrophy/drug therapy/physiopathology/diagnosis/psychology ; Tomography, Optical Coherence ; Surveys and Questionnaires ; Intravitreal Injections ; Sickness Impact Profile ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; Follow-Up Studies ; },
abstract = {OBJECTIVE: To evaluate the effect of pegcetacoplan on visual function and patient quality of life (QoL) measures based on distance of geographic atrophy (GA) lesions from the center of the fovea.<br><br>DESIGN: Post hoc analysis from OAKS and DERBY, two global, 24-month, multicenter, randomized, double-masked, sham-controlled phase 3 studies evaluating pegcetacoplan treatment for GA in age-related macular degeneration (AMD).<br><br>PARTICIPANTS: 888 study patients with GA for whom all data necessary for the post hoc analysis to be performed had been collected were included.<br><br>METHODS: Best-corrected visual acuity (BCVA) and 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) were assessed at baseline and every 4 and 6 months, respectively, to completion at month 24 in both pegcetacoplan-treated eyes and sham (observed) eyes. Eyes were stratified based on optical coherence tomography&#x2012;derived GA lesion location &#x2265;250 &#xb5;m (n = 192) or <250 &#xb5;m (n = 696) from the foveal center.<br><br>MAIN OUTCOME MEASURES: Change from baseline in BCVA and NEI VFQ-25 was evaluated over 24 months in GA lesions based on distance (&#x2265;250 or <250 &#xb5;m) from the foveal center. Adjustment was conducted via propensity score weighting, where model specification and baseline covariate selection were done a priori based on clinical rationale.<br><br>RESULTS: Pegcetacoplan-treated eyes with GA lesion margins &#x2265;250 &#xb5;m from the foveal center demonstrated directionally slower decline in visual acuity (mean +5.6 [SE 3.2] [P = .0785]) and QoL (mean +4.0 [SE 2.4] [P = .0905]) from baseline at 24 months compared with sham. The change in visual acuity (BCVA, mean -1.6 [SE 1.1] [P = .1522]) and QoL (NEI VFQ-25, -2.3 [1.1] [P = .0284]) in pegcetacoplan-treated eyes with GA lesion margins <250 &#xb5;m from the foveal center were within the limits of variability compared with sham.<br><br>CONCLUSIONS: Pegcetacoplan treatment demonstrated a potentially meaningful slower decline in visual acuity and QoL for patients with GA lesions &#x2265;250 &#xb5;m from the foveal center. The change in visual acuity and QoL seen with pegcetacoplan treatment for patients with GA lesions <250 &#xb5;m from the foveal center were within the limits of variability.},
}
@article {pmid40448050,
year = {2025},
author = {Lu, Y and Li, C and Liu, Y and Wu, T and Lu, P},
title = {Association between late age-related macular degeneration and dietary intake of copper, iron, zinc and selenium: a 2005-2008 NHANES cross-sectional observational study.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {327},
pmid = {40448050},
issn = {1471-2415},
support = {81671641//National Natural Science Foundation in China/ ; CXTDA2017039//Jiangsu Provincial Medical Innovation Team/ ; },
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; *Macular Degeneration/epidemiology/prevention &amp; control ; *Selenium/administration &amp; dosage ; *Zinc/administration &amp; dosage ; *Copper/administration &amp; dosage ; Middle Aged ; Aged ; Nutrition Surveys ; *Diet ; Aged, 80 and over ; Adult ; United States/epidemiology ; Prevalence ; *Trace Elements/administration &amp; dosage ; Risk Factors ; *Iron, Dietary/administration &amp; dosage ; Odds Ratio ; *Iron/administration &amp; dosage ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a significant global cause of visual impairment. Our study seeks to explore the relationship between the intake of copper, iron, zinc, selenium in diet and late AMD.<br><br>METHOD: In this cross-sectional study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted during 2005-2008. We employed three logistic regression models with or without adjustments to examine the association between dietary copper, iron, zinc, selenium and late AMD.<br><br>RESULT: Our study involved 4996 individuals aged 40 years and above with graded fundus pictures and dietary trace element intake data from a representative sample. The levels of copper intake were linked to a reduced risk of late AMD, resulting in odds ratios (OR) of 0.24 (95% confidence interval [CI]&#x2009;=&#x2009;0.13-0.46), 0.38 (95% CI&#x2009;=&#x2009;0.16-0.90), and 0.37 (95% CI&#x2009;=&#x2009;0.17-0.82) for crude model 1, adjusted model 2, and adjusted model 3 respectively. The intake levels of dietary iron, zinc and selenium showed an inverse correlation with the prevalence of late AMD in the crude model; ORs (95% CI) were as follows: Iron -&#x2009;0.92 (0.86, 0.97); Zinc- 0.88 (0.81, 0.96); Selenium- 0.98 (0.97, 0.99). However, in model 2 and 3, no significant association was observed between these three elements and late AMD. In subgroup analysis divided by age, there was only a significant inverse correlation observed between late AMD and copper intake in 70-85 years of age group.<br><br>CONCLUSION: Our findings suggest a higher dietary copper intake may be associated with a reduced risk of late AMD, with the protective effect remaining significant among individuals aged 70-85 years. While no significant association was identified between dietary intake of iron, zinc, selenium and AMD after adjusting for confounding factors. Further research is warranted to elucidate the mechanism underlying the relationship.},
}
@article {pmid40447166,
year = {2025},
author = {Huang, KC and Chiang, YF and Wang, KL and Huang, YJ and Shieh, TM and Ali, M and Hsia, SM},
title = {Hinokitiol Protects RPE cells from Oxidative and Autophagic Dysfunction: Implications for AMD Therapy.},
journal = {Free radical biology &amp; medicine},
volume = {237},
number = {},
pages = {76-87},
doi = {10.1016/j.freeradbiomed.2025.05.424},
pmid = {40447166},
issn = {1873-4596},
mesh = {Humans ; *Macular Degeneration/drug therapy/pathology/metabolism ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Autophagy/drug effects ; Hydrogen Peroxide/pharmacology/toxicity ; Reactive Oxygen Species/metabolism ; *Tropolone/analogs &amp; derivatives/pharmacology ; *Antioxidants/pharmacology ; *Monoterpenes/pharmacology ; Cell Survival/drug effects ; Membrane Potential, Mitochondrial/drug effects ; DNA Damage/drug effects ; Mitochondria/drug effects/metabolism ; Cell Line ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, driven by dysfunction of retinal pigment epithelial (RPE) cells. Oxidative stress-induced reactive oxygen species (ROS) play a critical role in AMD progression, although the underlying mechanisms remain unclear. Autophagy is essential for maintaining retinal homeostasis by clearing damaged organelles and misfolded proteins through lysosomal degradation. However, excessive ROS can disrupt autophagy balance, leading to the excessive degradation of cell components and ultimately triggering autophagy dysfunction-induced cell death. Hinokitiol, a natural compound derived from the heartwood of Cupressaceae plants, possesses potent antioxidant properties. This study aimed to investigate its roles against oxidative damage in RPE cells exposed to H2O2-induced ROS generation. Cell viability was assessed using MTT and crystal violet staining. ROS were measured using H2DCFDA and MitoSOX probes, while catalase activity was evaluated as indicator of antioxidant capacity. DNA damage was assessed by γ-H2AX immunocytochemistry and comet assay. Mitochondrial membrane potential (MMP) was analyzed using JC-1, and autophagy markers were examined by Western blotting. Hinokitiol significantly enhanced RPE cell viability, reduced ROS by increasing catalase activity, preserved mitochondrial function, and mitigated DNA damage. Furthermore, it restored autolysosome fusion impaired by H2O2, thereby maintaining cellular homeostasis. These findings suggest that hinokitiol may be a promising therapeutic candidate for AMD treatment.},
}
@article {pmid40446575,
year = {2025},
author = {Ganeshbabu, M and Manochkumar, J and Efferth, T and Ramamoorthy, S},
title = {Lutein: A natural defence combating age-related macular degeneration.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {143},
number = {},
pages = {156578},
doi = {10.1016/j.phymed.2025.156578},
pmid = {40446575},
issn = {1618-095X},
mesh = {*Lutein/therapeutic use/pharmacology ; Humans ; *Macular Degeneration/drug therapy/prevention &amp; control ; *Antioxidants/pharmacology/therapeutic use ; Dietary Supplements ; Microalgae/chemistry ; Animals ; NF-E2-Related Factor 2/metabolism ; },
abstract = {BACKGROUND: Recently, lutein has been gaining wide attention in the nutraceutical market due to its remarkable antioxidant and anti-inflammatory properties. Yet, about 200 million people across the globe are estimated to have age-related macular degeneration (AMD) that is highly correlated with lutein deficiency. Since lutein cannot be naturally synthesized in our body, it necessitates the intake of lutein through dietary supplements and diverse functional foods. With statistics supporting the fact that a massive group of the population is under the threat of AMD, it is the need of the hour to provide a palliative measure that is natural, effective, robust, and with minimal side effects. This review summarizes the potential of lutein as an effective measure that prevents the progression of AMD and emphasizes microalgae to be a reliable source for the commercialization of lutein.<br><br>HYPOTHESIS: Lutein is a natural curative to treat age-related macular degeneration.<br><br>RESULTS: Many epidemiological and clinical studies indicate the effective use of lutein to help prevent AMD. It is also inferred that several microalgae species are potent candidates compared to the other natural sources available for producing and commercializing lutein globally. Moreover, it has been figured out that lutein amplifies the translocation of Nrf2 into the nucleus and activates Nrf2 thereby supporting the hypothesized antioxidant pathway that takes place in the macular region of the eye.<br><br>CONCLUSION: Lutein, a carotenoid might considerably reduce the progression of AMD through its regular dietary consumption. Combinations of lutein along with zeaxanthin can be employed as supportive therapy as it may retard the advancement of AMD and other eye-related diseases. Though these facts might be convincing, the clarification regarding the exact mechanism of lutein in alleviating AMD needs to be further studied.},
}
@article {pmid40443830,
year = {2025},
author = {Cai, Y and Gu, Y and Zhang, J and Zhu, Y and Ma, Z and He, Q and Sun, Y and Yuan, M and Li, X and Zhu, K and Miao, B and Zhao, J and Liu, J and Tang, M and Tong, D and Feng, L and Ma, M and Zhong, G and Qiu, Z and Xue, T},
title = {An Engineered Intravitreal Injection Retinal-Pigment-Epithelium-Tropic Adeno-Associated Virus Vector Expressing a Bispecific Antibody Binding VEGF-A and ANG-2 Rescues Neovascular Age-Related Macular Degeneration in Animal Models and Patients.},
journal = {Research (Washington, D.C.)},
volume = {8},
number = {},
pages = {0717},
pmid = {40443830},
issn = {2639-5274},
abstract = {Antiangiogenesis gene therapy based on adeno-associated virus (AAV) vectors represents a promising advancement in the treatment of neovascular age-related macular degeneration (nAMD), providing an alternative to antibody-based therapies. However, the development of a safe and effective AAV vector capable of precisely targeting neovascularization and choroidal leakage remains a critical unmet need. In the present study, we engineered a novel intravitreally administered AAV vector with retinal-pigment-epithelium (RPE)-specific tropism. This vector demonstrated robust and localized gene expression in RPE cells while maintaining a favorable safety profile. The RPE-tropic AAV vector delivered a dual-acting antibody against vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG-2), exhibiting strong therapeutic efficacy and tolerability in both rodent and nonhuman primate choroidal neovascularization models. Based on the promising preclinical data, a single-center, single-arm, investigator-initiated trial (ChiCTR2400085329) was conducted to assess its safety and efficacy in patients with nAMD. The RPE-tropic AAV vector expressing anti-VEGF-A and anti-ANG-2 effectively alleviated disease progression and was well tolerated in the clinical setting. These findings highlight the potential of this engineered AAV-RPE capsid as a versatile platform for gene therapy, not only for nAMD but also for other ocular diseases involving RPE cells.},
}
@article {pmid40443784,
year = {2025},
author = {Arshad, MT and Maqsood, S and Ikram, A and Khan, AA and Raza, A and Ahmad, A and Gnedeka, KT},
title = {Encapsulation Techniques of Carotenoids and Their Multifunctional Applications in Food and Health: An Overview.},
journal = {Food science &amp; nutrition},
volume = {13},
number = {5},
pages = {e70310},
pmid = {40443784},
issn = {2048-7177},
abstract = {Carotenoids are a broad category of biologically active pigments in plants and animals with significant health associations, including immune-modulatory, anti-inflammatory, and antioxidant roles. They persuade prevention of illness through numerous mechanisms such as protection against oxidative stress, encouragement of cardiovascular and neuroprotective events, and reduction of diseases comprising cancer and macular degeneration. Carotenoids have several health benefits but are unstable, with low bioavailability, and easily degrade in environments containing light, heat, and oxygen. Since the encapsulation improves carotenoid solubility, stability, and controlled release, it has become a feasible strategy for overcoming these issues. This review considers a few encapsulation methods, including electrospinning, lipid-based delivery systems, spray drying, freeze drying, and supercritical fluid technology. Each of these methods is assessed in terms of their ability to retain carotenoids, improve bioavailability, and deliver targeted distribution. Evaluation of these methods has been made with the view of benefits, drawbacks, and suitability for industrial use. In conclusion, the analysis identifies current challenges in carotenoid encapsulation and potential future investigation and innovation directions in this area to exploit carotenoid-based functional foods, nutraceuticals, and medications.},
}
@article {pmid40442413,
year = {2025},
author = {Tang, F and Hogg, RE and Higgins, BE and Wright, DM and Smyth, L and Sivaprasad, S},
title = {Impact of Polygenic Risk Scores on Retinal Microstructures in Early and Intermediate Age-related Macular Degeneration: the Northern Ireland Sensory Aging Study.},
journal = {Eye (London, England)},
volume = {39},
number = {12},
pages = {2389-2397},
pmid = {40442413},
issn = {1476-5454},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Northern Ireland/epidemiology ; *Macular Degeneration/genetics/pathology/diagnosis ; *Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; Polymorphism, Single Nucleotide ; Risk Factors ; *Multifactorial Inheritance ; Genetic Risk Score ; },
abstract = {BACKGROUND: Although polygenic risk scores (PRSs) have been developed for age-related macular degeneration (AMD), it is not known whether these scores are associated with changes of retinal microstructures in early AMD. We compared retinal microstructures due to age-related changes in eyes with healthy macula in people aged 55 years or above versus those with early AMD and then determined the associations of retinal microstructural changes with AMD PRS.<br><br>METHODS: Participants aged 55 years or above with healthy macula and a group of people with early or intermediate AMD from the Northern Ireland Sensory Ageing study were included. 45 SNPs were included for PRS calculation.<br><br>RESULTS: A total of 470 participants with healthy macula were included (Beckman stage 0 or 1). The comparator group consisted of participants with early AMD (n&#x2009;=&#x2009;87) or intermediate AMD (n&#x2009;=&#x2009;48). We found that photoreceptor layer thickness decreased with age in all participants, while retinal pigment epithelium (RPE) layer thickness decreased only in those with apparently healthy macula (P&#x2009;<&#x2009;0.05). Higher PRS was associated with thinner photoreceptor and RPE layer thickness, larger drusen size and presence of soft drusen.<br><br>CONCLUSIONS: We observed a significant association between higher PRS and decreased photoreceptor layer thickness, irrespective of the macular status. Our study provides additional evidence supporting the role of genetics on pathological processes of AMD.},
}
@article {pmid40441379,
year = {2025},
author = {Berni, A and Foti, C and Bandello, F and Boscia, F and Breazzano, MP and Cicinelli, MV and Corradetti, G and Dolz-Marco, R and Feo, A and Gallego-Pinazo, R and Marolo, P and Russo, A and Sadda, SR and Sarraf, D and Soylu, C and Viggiano, P and Reibaldi, M and Borrelli, E},
title = {Predictors of Macular Atrophy after Serous Pigment Epithelial Detachment Collapse in Type 3 Macular Neovascularization and Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {11},
pages = {1126-1130},
doi = {10.1016/j.oret.2025.05.028},
pmid = {40441379},
issn = {2468-6530},
}
@article {pmid40438521,
year = {2025},
author = {Langlo, CS and Amin, A and Park, SS},
title = {Optical coherence tomography retinal imaging: narrative review of technological advancements and clinical applications.},
journal = {Annals of translational medicine},
volume = {13},
number = {2},
pages = {17},
pmid = {40438521},
issn = {2305-5839},
abstract = {BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide rapid cross-sectional images of the retina, cornea, and optic nerve head in live patients. The objective of this review is to provide an overview of the technical advancements and current clinical applications of OCT for managing patients with retinal disorders.<br><br>METHODS: Narrative overview synthesizing the findings of literature retrieved from searches of computerized database, authoritative texts and authors' clinical experience and expertise.<br><br>KEY CONTENT AND FINDINGS: Unlike the first-generation time-domain OCT (TD-OCT) instruments, the newer spectral-domain OCT (SD-OCT) instruments use a broadband light source to increase axial image resolution. In addition, the decreased image acquisition time also increases the transverse image resolution, reduces motion artifacts, and allows serial cross-sectional images of the retina to be obtained rapidly. A three-dimensional (3D) image of the retina, reconstructed using serial two-dimensional (2D) OCT images, can be used to quantitate retinal thickness and volume and perform analysis of retinal topography. Currently, commercial SD-OCT instruments are used routinely in clinical practice to obtain morphologic information used to diagnose and manage patients with various retinal disorders including macular degeneration and diabetic retinopathy. Newer swept-source OCT technology with faster image acquisition, provides wider field imaging of the peripheral retina. SD-OCT instruments can be incorporated into surgical microscopes to allow imaging of the retina during retinal surgery so that morphologic changes in the retina from surgical maneuvers can be observed in real time. More recently, OCT angiography (OCTA) has been developed which allows rapid, non-invasive 3D imaging of retinal and choroidal vascular flow. This is achieved by processing rapid serial SD-OCT images to detect movement of blood cells within vessels. Research has been done to further improve image resolution of SD-OCT to a cellular level by adding adaptive optics (AO) technology. The latest in SD-OCT technology is optoretinography (ORG), a technique to derive functional information from OCT images of the retina.<br><br>CONCLUSIONS: Advancement in OCT technology has made it possible to obtain high resolution retinal images that can provide anatomic, physiologic and functional information of the retina in live patients.},
}
@article {pmid40436797,
year = {2025},
author = {Inazu, A},
title = {Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia.},
journal = {Journal of atherosclerosis and thrombosis},
volume = {32},
number = {8},
pages = {911-923},
pmid = {40436797},
issn = {1880-3873},
mesh = {Humans ; *Cholesterol Ester Transfer Proteins/deficiency/antagonists &amp; inhibitors/genetics ; *Hyperlipoproteinemias/complications ; *Cholesterol Ester Storage Disease/complications/drug therapy ; *Atherosclerosis/etiology ; Cholesterol, HDL/blood ; Macular Degeneration/etiology ; Lipid Metabolism, Inborn Errors ; },
abstract = {Cholesteryl ester transfer protein (CETP) deficiency and lipoprotein phenotypes with CETP inhibitors were compared. The effects on atherosclerotic cardiovascular disease (ASCVD) and the recently suggested retinal disease of age-related macular degeneration (ARMD) were summarized and discussed in relation to CETP deficiency and extremely increased high-density lipoprotein (HDL) cholesterol levels (＞100 mg/dL). In CETP truncated variants leading to reduced low-density lipoprotein cholesterol levels, ASCVD risk was decreased in heterozygotes. ASCVD prevalence did not increase in homozygotes with CETP deficiency. However, the association between ASCVD and ARMD risks in cases of very high HDL cholesterol level found in multifactorial hyperalphalipoproteinemia needs to be clarified on an etiological basis. The hurdles facing the development of CETP inhibitors are summarized, including a new result for obicetrapib.},
}
@article {pmid40434931,
year = {2025},
author = {Tóth, A and Jeney, V},
title = {Hypoxia-Induced Changes in Endothelial Cell Phenotype and Function.},
journal = {Antioxidants &amp; redox signaling},
volume = {43},
number = {16-18},
pages = {849-868},
doi = {10.1089/ars.2025.1022},
pmid = {40434931},
issn = {1557-7716},
mesh = {Humans ; *Endothelial Cells/metabolism/cytology/pathology ; Animals ; Phenotype ; Reactive Oxygen Species/metabolism ; *Hypoxia/metabolism ; Cell Hypoxia ; },
abstract = {Significance: Endothelial cells (ECs) are specialized cells lining the interior surface of blood vessels, playing a crucial role in vascular biology. They exhibit remarkable versatility, adapting to various tissue requirements. Their ability to respond to physiological and pathological stimuli ensures proper tissue function and homeostasis. Recent Advances: Hypoxia is when the oxygen level in a given organ, tissue, or cell type drops below the physiological level and is insufficient to maintain adequate homeostasis. ECs respond to hypoxia by activating various mechanisms. Hypoxia-induced changes in ECs can promote survival in low-oxygen environments by altering cellular metabolism and inducing neoangiogenesis. However, hypoxia-induced EC responses can also be detrimental, leading to increased production of reactive oxygen species, heightened inflammation, changes in vascular tone, increased permeability of the endothelial barrier, and a higher risk of coagulation. Critical Issues: Hypoxia-induced EC responses contribute to the pathogenesis of various diseases, including metabolic diseases (e.g., diabetes, chronic kidney disease), infectious diseases, chronic inflammation, neoplastic diseases, cardiovascular diseases (e.g., atherosclerosis, myocardial infarction, and stroke) lung diseases (e.g., chronic obstructive pulmonary disease and pulmonary hypertension), eye diseases (age-related macular degeneration and retinopathy), and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease). Future Directions: Detailed, disease-specific investigations are essential to delineate how endothelial hypoxia responses contribute to various pathologies. Understanding these mechanisms could reveal whether targeting endothelial hypoxia holds therapeutic potential. Antioxid. Redox Signal. 43, 849-868.},
}
@article {pmid40434533,
year = {2025},
author = {Phillips, R},
title = {Diet, Mitochondrial Dysfunction, Vascular Endothelial Damage, and the Microbiome: Drivers of Ocular Degenerative and Inflammatory Diseases.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {7},
pages = {1429-1452},
pmid = {40434533},
issn = {2193-8245},
abstract = {There is abundant evidence in medical literature that Western diet and lifestyle drive the cellular and metabolic processes which underlie chronic non-communicable diseases. However, non-pharmaceutical interventions, which focus on nutrition, the microbiome and lifestyle, to prevent non-communicable diseases are not part of mainstream treatment, for a variety of reasons. Lack of progress in stemming the rise in chronic non-communicable diseases can be attributed to the current 'downstream' medical paradigm which is focused on treating disease and symptoms, rather than preventing disease via an 'upstream' approach, which looks at cause and process. Metabolic abnormalities and obesity have previously been noted as correlated with common chronic ophthalmic conditions such as age related macular degeneration (AMD), glaucoma, ocular inflammation, diabetic retinopathy and retinal vascular occlusive disease. These are ocular manifestations of an underlying common cause. The aim of this paper, using an ophthalmic context, is to provide an overview of the cellular pathophysiological mechanisms that underlie chronic non-communicable diseases, including ophthalmic diseases, and to draw the links between diet and lifestyle, the microbiome and chronic non-communicable diseases.},
}
@article {pmid40434532,
year = {2025},
author = {Ohnaka, M and Sakurada, Y and Hayashi, A and Kadonosono, K and Ohno, H and Mori, R and Matsumoto, H and Nagamori, I and Murata, Y and Maio-Twofoot, T and Karcher, H and Takahashi, H},
title = {Real-World Outcomes of Brolucizumab Treatment in Japanese Patients with Neovascular Age-Related Macular Degeneration: A 12-Month, Multicenter Study.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {7},
pages = {1551-1565},
pmid = {40434532},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this study was to evaluate the real-world outcomes of brolucizumab use in Japanese patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: PHEASANT was a retrospective, multicenter, single-arm cohort study. The study included 438 patients, of whom 123 were treatment-na&#xef;ve and 315 were pre-treated. The primary outcome was retinal fluid (subretinal fluid [SRF] and intraretinal fluid [IRF]) resolution at month 12, with change in visual and retinal anatomy parameters and safety assessed as key secondary outcomes.<br><br>RESULTS: At baseline in the treatment-na&#xef;ve cohort, 10.1% (n&#x2009;=&#x2009;7/69) of patients were free of retinal fluid, increasing to 62.3% (n&#x2009;=&#x2009;43/69) at month 12. In the pre-treated cohort, 14.9% (n&#x2009;=&#x2009;30/201) of patients were free of retinal fluid at baseline, increasing to 43.8% (n&#x2009;=&#x2009;88/201) at month 12. The median (interquartile range [IQR]) injection interval for pre-treated patients at month 12 was extended by 21 (7.0-35.0) days. The overall intraocular inflammation rate (including the rate of retinal vasculitis/retinal occlusive vasculitis of 0.46% [2/438]) was 8.4% (n&#x2009;=&#x2009;37/438).<br><br>CONCLUSION: In a real-world clinical setting, brolucizumab was effective at drying the retina in treatment-na&#xef;ve and pre-treated Japanese nAMD patients and therefore has the potential to reduce the treatment burden by prolonging injection intervals. Safety outcomes support the overall favorable benefit/risk profile of brolucizumab.<br><br>GOV IDENTIFIER: NCT06699914.},
}
@article {pmid40434460,
year = {2025},
author = {Karabulut, S and Kaderli, ST and Karalezli, A},
title = {Long-term outcomes of drusenoid retinal pigment epithelium detachment in eyes with age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {6},
pages = {843-846},
pmid = {40434460},
issn = {1998-3689},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/etiology ; *Visual Acuity ; *Retinal Detachment/diagnosis/etiology ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; Aged ; *Fluorescein Angiography/methods ; Fundus Oculi ; *Macular Degeneration/complications/diagnosis ; Middle Aged ; Time Factors ; },
abstract = {PURPOSE: We aim to evaluate the changes in the size of drusens and drusenoid pigment epithelial detachments (PED) in patients with age-related macular degeneration.<br><br>DESIGN: This study was designed as an observational retrospective cohort study.<br><br>METHODS: We evaluated eyes with drusenoid PED tracked using spectral-domain and enhanced depth imaging optical coherence tomography. The cases were classified according to the follow-up visits and divided into two groups as eyes with collapsed PED and persisting PED. The best-corrected visual acuity (BCVA), size of drusens and PED, central macular thickness (CMT), and subfoveal choroidal thickness (SCT) were recorded.<br><br>RESULTS: We included 11 patients' 22 eyes with drusenoid PED. In the final comparison, the mean CMT, SCT, and BCVA were significantly lower in Group 1 compared to Group 2 (P = 0.05; P = 0.05; P = 0.002, respectively). The mean CMT, SCT, and BCVA were significantly decreased from baseline to the last visit in Group 1 (P = 0.013; P < 0.001; P = 0.001, respectively). No significant changes were observed regarding the mean CMT, SCT, and BCVA in Group 2 during the follow-up visits. (P = 0.317, P = 0.682, P = 0.056).<br><br>CONCLUSION: Spontaneous collapse of drusenoid PED is associated with poor visual outcome.},
}
@article {pmid40434361,
year = {2025},
author = {Pushin, DA and Garrad, DV and Kapahi, C and Silva, AE and Chahal, P and Cory, DG and Kulmaganbetov, M and Salehi, I and Mungalsingh, MA and Singh, T and Thompson, B and Yu, D and Sarenac, D},
title = {Characterizing the circularly oriented macular pigment using spatiotemporal sensitivity to structured light entoptic phenomena.},
journal = {Journal of vision},
volume = {25},
number = {6},
pages = {11},
pmid = {40434361},
issn = {1534-7362},
mesh = {Humans ; *Macular Pigment/physiology/metabolism ; Adult ; Photic Stimulation/methods ; Male ; Female ; Psychophysics/methods ; Sensory Thresholds/physiology ; *Light ; *Macula Lutea/physiology ; },
abstract = {To characterize the optical density of circularly oriented macular pigment (MP) in the human retina, as a quantification of macular health, Psychophysical discrimination tests were performed on human subjects using structured light-induced entoptic phenomena. Central exclusions were used to determine the visual extents of stimuli with varying spatiotemporal frequencies. A model was developed to describe the action of circularly oriented MP, and map stimuli to perceived sizes. The experimental results provided validation for the computational model, showing good agreement between measured data and predictions with a Pearson χ2 fit statistic of 0.06. This article contains a description of a new quantification of macular health and the necessary tools for clinical development. The integration of structured light into vision science has led to the development of more selective and versatile entoptic probes of eye health that provide interpretable thresholds of structured light perception. This work develops a model that maps perceptual thresholds of entoptic phenomena to the underlying MP structure that supports its perception. We selectively characterize the circularly oriented MP optical density, rather than the total MP optical density as typically measured. The presented techniques can be applied in novel early diagnostic tests for a variety of diseases related to macular degeneration such as age-related macular degeneration, macular telangiectasia, and pathological myopia. This work both provides insights into the microstructure of the human retina and uncovers a new quantification of macular health.},
}
@article {pmid40434345,
year = {2025},
author = {Gong, J and Chan, KS and Rajesh, A and Droho, S and Lavine, JA},
title = {Adrb2 Expression in Ocular-Infiltrating Macrophages Is Necessary for Interleukin-6 Expression and Choroidal Neovascularization.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {5},
pages = {43},
pmid = {40434345},
issn = {1552-5783},
support = {K08 EY030923/EY/NEI NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R01 EY034486/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Choroidal Neovascularization/metabolism/genetics/pathology ; *Interleukin-6/biosynthesis/genetics/metabolism ; *Macrophages/metabolism ; Mice ; *Receptors, Adrenergic, beta-2/genetics/biosynthesis ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; *Gene Expression Regulation/physiology ; },
abstract = {PURPOSE: Effective therapies for treatment resistant neovascular age-related macular degeneration (nAMD) remain an unmet need. Beta-adrenergic receptor (AR) blockers can decrease laser-induced choroidal neovascularization (CNV) size in mice. We have shown that monocyte-derived macrophages (MDMs) and interleukin-6 (IL-6) are necessary for beta-AR blockers to inhibit CNV. However, the specific beta-AR and the mechanism of this pathway are not fully elucidated. We hypothesized that beta2-AR (Adrb2) signaling on MDMs increases IL-6 production and stimulates CNV.<br><br>METHODS: Previously published single-cell RNA-sequencing data was reanalyzed to determine which mononuclear phagocytes express beta-ARs. Adrb2flox/flox: Cx3cr1CreER/+ mice (Adrb2&#x394;Macs) or Adrb2flox/flox (Adrb2flox) controls were given tamoxifen injections at either four weeks before or at the time of laser-induced CNV to knockout Adrb2 in tissue resident or all macrophages, respectively. Mice underwent laser induced-CNV, and eyes were collected for choroidal wholemount immunofluorescence imaging to measure CNV area, multiparameter flow cytometry to analyze macrophage heterogeneity, and ELISAs to quantitate IL-6 levels.<br><br>RESULTS: Adrb2 was the predominantly expressed beta-AR and was found on microglia, macrophages, and monocytes. Adrb2 deletion in tissue resident macrophages had no effect upon CNV area. Adrb2 deletion in all macrophages decreased CNV area by 1.4-fold. Adrb2&#x394;Macs posterior eye cups demonstrated similar levels of pro-angiogenic CD11c+ macrophages compared to Adrb2flox controls, but Ly6CnegCD11cneg macrophages were significantly increased. IL-6 levels increased with laser in Adrb2flox controls, but IL-6 levels in Adrb2&#x394;Macs posterior eye cups were unchanged.<br><br>CONCLUSIONS: Beta2-AR deletion in ocular-infiltrating macrophages decreases laser-induced CNV area. Beta2-AR expression regulates IL-6 expression in monocyte-derived macrophages.},
}
@article {pmid40433417,
year = {2025},
author = {Gui, C and Gao, Y and Zhang, R and Zhou, G},
title = {Bioinformatics Analysis of Lactylation-related Biomarkers and Potential Pathogenesis Mechanisms in Age-related Macular Degeneration.},
journal = {Current genomics},
volume = {26},
number = {3},
pages = {191-209},
pmid = {40433417},
issn = {1389-2029},
abstract = {BACKGROUND: Lactylation is increasingly recognized to play a crucial role in human health and diseases. However, its involvement in age-related macular degeneration (AMD) remains largely unclear.<br><br>OBJECTIVES: The aim of this study was to identify and characterize the pivotal lactylation-related genes and explore their underlying mechanism in AMD.<br><br>METHODS: Gene expression profiles of AMD patients and control individuals were obtained and integrated from the GSE29801 and GSE50195 datasets. Differentially expressed genes (DEGs) were screened and intersected with lactylation-related genes for lactylation-related DEGs. Machine learning algorithms were used to identify hub genes associated with AMD. Subsequently, the selected hub genes were subject to correlation analysis, and reverse transcription quantitative real-time PCR (RT-qPCR) was used to detect the expression of hub genes in AMD patients and healthy control individuals.<br><br>RESULTS: A total of 68 lactylation-related DEGs in AMD were identified, and seven genes, including HMGN2, TOP2B, HNRNPH1, SF3A1, SRRM2, HIST1H1C, and HIST1H2BD were selected as key genes. RT-qPCR analysis validated that all 7 key genes were down-regulated in AMD patients.<br><br>CONCLUSION: We identified seven lactylation-related key genes potentially associated with the progression of AMD, which might deepen our understanding of the underlying mechanisms involved in AMD and provide clues for the targeted therapy.},
}
@article {pmid40431274,
year = {2025},
author = {Schiavone, N and Isoldi, G and Calcagno, S and Rovida, E and Antiga, E and De Almeida, CV and Lulli, M},
title = {Exploring the Gut Microbiota-Retina Axis: Implications for Health and Disease.},
journal = {Microorganisms},
volume = {13},
number = {5},
pages = {},
pmid = {40431274},
issn = {2076-2607},
abstract = {The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.},
}
@article {pmid40430474,
year = {2025},
author = {Vailoces, VAS and Tolentino, AJ and Arevalo, JF and Adelman, RA and Bhisitkul, R and Do, DV and Nguyen, QD and Tolentino, MJ and Tanito, M and Serizawa, H},
title = {Development of Rifampicin Eye Drops for the Treatment of Exudative Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {5},
pages = {},
pmid = {40430474},
issn = {1424-8247},
support = {N/A//AMD Therapeutics LLC/ ; N/A//NeoVascularX, Inc/ ; },
abstract = {Background/Objectives: Exudative age-related macular degeneration (AMD) is a disease of choroidal neovascularization that causes blindness. Current treatments to preserve vision in this prevalent and blinding condition are repeat intraocular injections of anti-vascular endothelial growth factor medicines for a patient's lifetime to preserve and prevent vision loss leading to blindness. Rifampicin, a small-molecule antibiotic, has previously been reported to exhibit anti-angiogenic properties and a topical safety profile that is well-tolerated. Based on this evidence, we investigated the feasibility of formulating rifamycin as an ophthalmic drop capable of delivering therapeutic concentrations to the posterior segment of the eye. Methods: Inhibition of neovascularization by administration of rifampicin was analyzed in the rat oxygen-induced retinopathy (OIR) and mouse laser-induced choroidal neovascularization (CNV) models. Pharmacokinetic (PK) studies were conducted in mice, rats, and rabbits by dosing various formulations containing rifampicin, and the compound was quantified by LC/MS analysis. Results: Results from dose escalation studies in the mouse laser-induced CNV model suggested the minimum effective dose of rifampicin required for inhibiting neovascularization in subretinal tissues to be 0.7 mg/kg, which is substantially lower than the 20 mg/kg dosage approved for infectious disease treatments. The previous studies did not report the minimum effective dose in the anti-angiogenesis effects. The effective area under the concentration-time curve (AUC) in the sub-retina was evaluated as 0.27 h·ng/mg. In rabbits, rifampicin was delivered to the sub-retina by a single topical application of various formulations in a dose-dependent manner. The topical application of the formulations containing 1% rifampicin, which was well-tolerated in clinical trials previously reported for ocular trachoma, achieved subretinal delivery approximately 2-32 times greater than the effective AUC. Plasma exposure of the compound by the topical application was evaluated to range approximately 0.5-10 ng/mL. Conclusions: Rifampicin was delivered to the sub-retina in rabbits with an efficiency greater than the effective dose required for inhibiting neovascularization. Limited amounts of plasma exposure by the topical application were detected. These results suggested the therapeutic potential of the rifampicin formulations for the topical treatment of exudative macular degeneration.},
}
@article {pmid40429992,
year = {2025},
author = {Heloterä, H and Kostanek, J and Liukkonen, M and Siintamo, L and Linna-Kuosmanen, S and Watala, C and Blasiak, J and Kaarniranta, K},
title = {Serum RNA Profile Reflects Fluid Status and Atrophic Retinal Changes in Neovascular Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40429992},
issn = {1422-0067},
support = {333302//Academy of Finland/ ; //Sigrid Juselius Foundation/ ; //Finnish Eye Foundation/ ; 5503770//Kuopio University VTR grant/ ; //Aarne Koskelo Foundation/ ; //Finnish Eye and Tissue Bank Foundation/ ; //Mary &amp; Georg C. Ehrnrooth Foundation/ ; },
mesh = {Humans ; Aged ; Female ; Male ; *Macular Degeneration/blood/pathology/genetics ; *Retina/pathology/metabolism ; *RNA/blood ; Tomography, Optical Coherence ; Aged, 80 and over ; Biomarkers/blood ; *Wet Macular Degeneration/blood/genetics/pathology ; },
abstract = {The increasing prevalence of age-related macular degeneration (AMD), a disease that can result in the loss of central vision, is an emerging problem worldwide due to aging societies. Growing patient numbers create a challenge for the healthcare system. Understanding the mechanisms of AMD pathogenesis will aid in early, personalized, and efficient intervention, helping to mitigate this issue. Current diagnostic methods rely on optical coherence tomography and angiography imaging, which identify existing damages, but do not provide information on the mechanisms behind them. In the present work, we demonstrate a difference in the serum RNA profile between neovascular AMD (nAMD) patients and controls. Moreover, the RNA profile of nAMD patients corresponded with anatomical changes in the retinal fluid compartments as well as atrophic changes of the retina. We followed two independent ways to control false positive leads, and when these approaches were combined, thioredoxin-related transmembrane protein 4 (TMX4) was observed to be differentially expressed by both approaches. This finding opens a new pathway in AMD studies, which are limited due to restricted access to live human target material and the limited value of animal models of human AMD.},
}
@article {pmid40429443,
year = {2025},
author = {Wolfrum, P and Böhm, EW and König, S and Lorenz, K and Stoffelns, B and Korb, CA},
title = {Safety and Long-Term Efficacy of Intravitreal rtPA, Bevacizumab and SF6 Injection in Patients with Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {10},
pages = {},
pmid = {40429443},
issn = {2077-0383},
abstract = {Purpose: Acute submacular hemorrhage (SMH) is a vision-threatening complication common in patients affected by age-related macular degeneration (AMD). This study evaluates safety, long-term clinical outcomes and associated treatment factors following intravitreal triple injection of recombinant tissue plasminogen activator (rtPA), SF6 gas, and Bevacizumab due to acute SMH secondary to AMD. Methods: A retrospective analysis on patients who received treatment between January 2014 and December 2020 (n = 37) was conducted. Visual acuity (VA), central retinal thickness (CRT), central retinal volume (CRV), and axial pigment epithelial detachment height were analyzed at baseline (B), 4 weeks after triple injection (FU1), after the following anti-VEGF injection series (FU2), after 1 year (FU3), after 2 years (FU4), and at the final follow-up examination after 4.4 ± 1.6 years (FU5). Further, treatment courses and clinical outcomes were compared to a patient cohort treated for exudative AMD without prior SMH. Furthermore, an explorative data analysis on final VA was conducted, and adverse events following triple therapy were investigated. Results: Triple injection was performed on average 5.6 ± 5.7 days after onset of symptoms. Patients received 16 ± 3 additional intravitreal anti-VEGF injections due to persistent macular edema over the subsequent 2 years. Significant improvements were observed at FU1 in VA (p < 0.001), CRT (p = 0.005), and CRV (p = 0.007), as well as at FU2 in axial PED height (p < 0.001), with all improvements being stable until final follow-up examination. In the group comparison, patients with SMH demonstrated significantly worse functional and anatomical outcomes at 24 months except for the 24-month CRT, and patients on average received more intravitreal injections. Five of 37 patients (13.5%) experienced a retinal pigment epithelial tear following triple injection. Final VA correlated positively and significantly with FU1 VA, while no correlation was observed with baseline VA, the size or height of SMH, or the number of additional anti-VEGF injections. Conclusions: Triple injection constitutes a simple and effective therapy with long-term functional and anatomical improvements following treatment due to SMH, although patients have an increased risk for RPE tears. The 4-week postoperative VA following triple injection was predictive for long-term visual function.},
}
@article {pmid40428724,
year = {2025},
author = {Gong, CS},
title = {Advances in Electrode Design and Physiological Considerations for Retinal Implants.},
journal = {Micromachines},
volume = {16},
number = {5},
pages = {},
pmid = {40428724},
issn = {2072-666X},
support = {113-2221-E-008 -117 -MY3//National Science and Technology Council of Taiwan/ ; },
abstract = {Until now, the ultimate solution for blind people has not been achieved, because challenges still exist. Retinal implants have emerged as a promising solution for restoring vision in individuals suffering from retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Central to the efficacy of these implants is the design and functionality of the electrode arrays responsible for stimulating retinal neurons. This review evaluates the evolution of retinal implants, with particular emphasis on electrode specifications, physiological considerations for electrical stimulation, and recent advancements in electrode design. A comprehensive analysis of state-of-the-art published studies provides a detailed cross-comparison of electrode characteristics, offering insights into current state-of-the-art technologies and future directions.},
}
@article {pmid40428167,
year = {2025},
author = {Wang, MH},
title = {Integrating Artificial Intelligence and Precision Therapeutics for Advancing the Diagnosis and Treatment of Age-Related Macular Degeneration.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
pmid = {40428167},
issn = {2306-5354},
support = {U22A2041, 62372047//National Natural Science Foundation of China/ ; ZDSYS20220422103800001//Shenzhen Key Laboratory of Intelligent Bioinformatics/ ; KQTD20200820113106007//Shenzhen Science and Technology Program/ ; 2024KTSCX226//Characteristic Innovation Project of Ordinary Universities in Guangdong Province/ ; },
abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease influenced by complex molecular mechanisms, including genetic susceptibility, inflammation, oxidative stress, and metabolic dysregulation. While substantial progress has been made in understanding its pathogenesis, the full molecular underpinnings of AMD remain unclear, impeding the effectiveness of current therapeutic strategies. This study provides an in-depth exploration of the molecular interactions involved in AMD progression, particularly focusing on genetic predispositions (such as CFH, ARMS2/HTRA1, and APOE), inflammatory pathways (including complement system dysregulation and cytokine responses), lipid metabolism (e.g., cholesterol homeostasis and drusen formation), and angiogenesis (VEGF signaling). Through a systematic review and bibliometric analysis of literature published between 2015 and 2025, the study identifies emerging research trends, existing gaps, and promising future therapeutic directions. It further investigates innovative precision medicine approaches, including gene editing (CRISPR), RNA therapeutics (siRNA, antisense oligonucleotides), immunomodulatory therapies, and nanotechnology-based drug delivery systems. Additionally, the study examines the role of metabolic disorders such as diabetes and dyslipidemia in AMD progression, highlighting the influence of systemic health factors on disease onset. Finally, the potential of artificial intelligence (AI) in enhancing AMD management through biomarker-based risk stratification, predictive modeling, and personalized treatment optimization is assessed. By mapping the intricate molecular networks underlying AMD and evaluating novel therapeutic strategies, this research aims to contribute to the development of more effective, individualized treatment protocols for patients with AMD.},
}
@article {pmid40428094,
year = {2025},
author = {Chatzara, A and Maliagkani, E and Mitsopoulou, D and Katsimpris, A and Apostolopoulos, ID and Papageorgiou, E and Georgalas, I},
title = {Artificial Intelligence Approaches for Geographic Atrophy Segmentation: A Systematic Review and Meta-Analysis.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
pmid = {40428094},
issn = {2306-5354},
abstract = {Geographic atrophy (GA) is a progressive retinal disease associated with late-stage age-related macular degeneration (AMD), a significant cause of visual impairment in senior adults. GA lesion segmentation is important for disease monitoring in clinical trials and routine ophthalmic practice; however, its manual delineation is time-consuming, laborious, and subject to inter-grader variability. The use of artificial intelligence (AI) is rapidly expanding within the medical field and could potentially improve accuracy while reducing the workload by facilitating this task. This systematic review evaluates the performance of AI algorithms for GA segmentation and highlights their key limitations from the literature. Five databases and two registries were searched from inception until 23 March 2024, following the PRISMA methodology. Twenty-four studies met the prespecified eligibility criteria, and fifteen were included in this meta-analysis. The pooled Dice similarity coefficient (DSC) was 0.91 (95% CI 0.88-0.95), signifying a high agreement between the reference standards and model predictions. The risk of bias and reporting quality were assessed using QUADAS-2 and CLAIM tools. This review provides a comprehensive evaluation of AI applications for GA segmentation and identifies areas for improvement. The findings support the potential of AI to enhance clinical workflows and highlight pathways for improved future models that could bridge the gap between research settings and real-world clinical practice.},
}
@article {pmid40428060,
year = {2025},
author = {Devine, BC and Dogan, AB and Sobol, WM},
title = {Recent Optical Coherence Tomography (OCT) Innovations for Increased Accessibility and Remote Surveillance.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {5},
pages = {},
pmid = {40428060},
issn = {2306-5354},
abstract = {Optical Coherence Tomography (OCT) has revolutionized the diagnosis and management of retinal diseases, offering high-resolution, cross-sectional imaging that aids in early detection and continuous monitoring. However, traditional OCT devices are limited to clinical settings and require a technician to operate, which poses accessibility challenges such as a lack of appointment availability, patient and family burden of frequent transportation, and heightened healthcare costs, especially when treatable pathology is undetected. With the increasing global burden of retinal conditions such as age-related macular degeneration (AMD) and diabetic retinopathy, there is a critical need for improved accessibility in the detection of retinal diseases. Advances in biomedical engineering have led to innovations such as portable models, community-based systems, and artificial intelligence-enabled image analysis. The SightSync OCT is a community-based, technician-free device designed to enhance accessibility while ensuring secure data transfer and high-quality imaging (6 × 6 mm resolution, 80,000 A-scans/s). With its compact design and potential for remote interpretation, SightSync widens the possibility for community-based screening for vision-threatening retinal diseases. By integrating innovations in OCT imaging, the future of monitoring for retinal disease can be transformed to reduce barriers to care and improve patient outcomes. This article discusses the evolution of OCT technology, its role in the diagnosis and management of retinal diseases, and how novel engineering solutions like SightSync OCT are transforming accessibility in retinal imaging.},
}
@article {pmid40427478,
year = {2025},
author = {Falcão, AS and Pedro, ML and Tenreiro, S and Seabra, MC},
title = {Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
pmid = {40427478},
issn = {2076-3921},
support = {NASCENT HR22-00569//CaixaBank/ ; Research Unit UID/04462 and Associated Laboratory LS4FUTURE (LA/P/0087/2020)//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western world, and it currently lacks effective therapy. It is believed that AMD initiates in the aged retinal pigment epithelium (RPE), which presents lysosomal dysfunction and oxidative stress (OxS) that ultimately leads to RPE damage and AMD progression. AMD is a complex pathology, so multitarget treatments are required to act on different pathways, presenting several challenges. In this review, we discuss the current knowledge on the pathogenesis of this disease, focusing mainly on lysosomal dysfunction and OxS. Because transcription factors regulate homeostasis, the transcription factor EB (TFEB), which controls lysosomal function and biogenesis, and the nuclear factor erythroid 2-related factor 2 (NRF2), which manages OxS, have been proposed as promising targets for disease intervention. Finally, we discuss the interplay of these pathways for a potential synergistic effect on AMD-targeted therapies, as they could change the course of today's available treatments for AMD.},
}
@article {pmid40427443,
year = {2025},
author = {Pu, N and Li, S and Wu, H and Zhao, N and Wang, K and Wei, D and Wang, J and Sha, L and Zhao, Y and Tao, Y and Song, Z},
title = {Beacon of Hope for Age-Related Retinopathy: Antioxidative Mechanisms and Pre-Clinical Trials of Quercetin Therapy.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
pmid = {40427443},
issn = {2076-3921},
support = {221100310200//Science and Technology Major Project of Henan Province/ ; 224200510013//Zhongyuan Science and Technology Leading Talent Project/ ; },
abstract = {Age-related retinopathy is one of the leading causes of visual impairment and irreversible blindness, characterized by progressive neuronal and myelin loss. The damages caused by oxidation contributes to the hallmarks of aging and represents fundamental components in pathological pathways that are thought to drive multiple age-related retinopathies. Quercetin (Que), a natural polyphenol abundant in vegetables, herbs, and fruits, has been extensively studied for its long-term antioxidative effects mediated through diverse mechanisms. Additionally, Que and its derivatives exhibit a broad spectrum of pharmacological characteristics in the cellular responses of age-related retinopathy induced by oxidative stress, including anti-inflammatory, anti-neovascularization, regulatory, and neuroprotective effects in autophagy and apoptosis processes. This review mainly focuses on the antioxidative mechanisms and curative effects of Que treatment for various age-related retinopathies, such as retinitis pigmentosa, diabetic retinopathy, age-related macular degeneration, and glaucoma. Furthermore, we discuss emerging technologies and methods involving Que and its derivatives in the therapeutic strategies for age-related retinopathies, highlighting their promise for clinical translation.},
}
@article {pmid40426994,
year = {2025},
author = {Arthur, P and Kandoi, S and Kalvala, A and Boirie, B and Nathani, A and Aare, M and Bhattacharya, S and Kulkarni, T and Sun, L and Lamba, DA and Li, Y and Singh, M},
title = {Cannabidiol-Loaded Retinal Organoid-Derived Extracellular Vesicles Protect Oxidatively Stressed ARPE-19 Cells.},
journal = {Biomedicines},
volume = {13},
number = {5},
pages = {},
pmid = {40426994},
issn = {2227-9059},
support = {R01 NS125016/NS/NINDS NIH HHS/United States ; U54 MD007582/MD/NIMHD NIH HHS/United States ; R16 GM149462/GM/NIGMS NIH HHS/United States ; 5R16GM149462-01//National Institute of Health/ ; G12 MD007582/MD/NIMHD NIH HHS/United States ; R01NS125016/NH/NIH HHS/United States ; },
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is the third leading cause of irreversible blindness in elderly individuals aged over 50 years old. Oxidative stress plays a crucial role in the etiopathogenesis of multifactorial AMD disease. The phospholipid bilayer EVs derived from the culture-conditioned medium of human induced pluripotent stem cell (hiPSC) differentiated retinal organoids aid in cell-to-cell communication, signaling, and extracellular matrix remodeling. The goal of the current study is to establish and evaluate the encapsulation of a hydrophobic compound, cannabidiol (CBD), into retinal organoid-derived extracellular vesicles (EVs) for potential therapeutic use in AMD. Methods: hiPSC-derived retinal organoid EVs were encapsulated with CBD via sonication (CBD-EVs), and structural features were elucidated using atomic force microscopy, nanoparticle tracking analysis, and small/microRNA (miRNA) sequencing. ARPE-19 cells and oxidative-stressed (H2O2) ARPE-19 cells treated with CBD-EVs were assessed for cytotoxicity, apoptosis (MTT assay), reactive oxygen species (DCFDA), and antioxidant proteins (immunohistochemistry and Western blot). Results: Distinct miRNA cargo were identified in early and late retinal organoid-derived EVs, implicating their roles in retinal development, differentiation, and functionality. The therapeutic effects of CBD-loaded EVs on oxidative-stressed ARPE-19 cells showed greater viability, decreased ROS production, downregulated expression of inflammation- and apoptosis-related proteins, and upregulated expression of antioxidants by Western blot and immunocytochemistry. Conclusions: miRNAs are both prognostic and predictive biomarkers and can be a target for developing therapy since they regulate RPE physiology and diseases. Our findings indicate that CBD-EVs could potentially alleviate the course of AMD by activating the targeted proteins linked to the adenosine monophosphate kinase (AMPK) pathway. Implicating the use of CBD-EVs represents a novel frontline to promote long-term abstinence from drugs and pharmacotherapy development in treating AMD.},
}
@article {pmid40425125,
year = {2025},
author = {Kah, TA},
title = {A Bayesian approach to investigating presumed retinal micro(nano)plastics.},
journal = {Bio Systems},
volume = {253},
number = {},
pages = {105502},
doi = {10.1016/j.biosystems.2025.105502},
pmid = {40425125},
issn = {1872-8324},
mesh = {Bayes Theorem ; Humans ; *Retina/pathology/diagnostic imaging ; Tomography, Optical Coherence/methods ; Retinal Diseases ; },
abstract = {The human retina, a highly vascularized, metabolically active, and immunologically privileged neural tissue, stands in contrast to the ubiquity of micro(nano)plastics (MNPs), which have been reported in every other organ system. Despite this, the presence of MNPs in the retina remains undocumented, a critical gap given their potential to contribute to local inflammation, microvascular occlusion, or act as cofactors in diseases such as diabetic retinopathy, age-related macular degeneration, or uveitis. Furthermore, the diverse physicochemical properties of MNPs - including their varying sizes, shapes, colors, and optical characteristics - raise the intriguing possibility that their presence within the retina could mimic commonly observed ophthalmic features. I hypothesize that certain features-previously attributed to other causes-such as tiny discrete foci in fundus photography and hyperreflective retinal foci in optical coherence tomography, may actually contain MNPs. This hypothesis carries significant biological implications not only for ophthalmology but also for environmental toxicology and public health. To formally evaluate its plausibility, I constructed a Bayesian model incorporating initial skepticism and considering varying likelihoods of observed evidence under both null and alternative assumptions. The model demonstrates that even with an extremely low prior probability, the reproducibility and discernible patterns of certain imaging findings can justify a significantly increased posterior belief, thus warranting further scientific inquiry. This work offers a probabilistic framework to re-evaluate retinal anomalies and encourages empirical investigation in environmental ophthalmology, without definitively proving MNP presence. The development of retinal imaging techniques for the specific detection of MNPs could provide a valuable tool for environmental toxicology, preventive medicine, and public health by offering a non-invasive biomarker for systemic MNPs exposure.},
}
@article {pmid40424622,
year = {2025},
author = {Bedell, HE},
title = {Letter to the editor: The photochromatic interval in age-related macular degeneration.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {102},
number = {7},
pages = {472-474},
doi = {10.1097/OPX.0000000000002266},
pmid = {40424622},
issn = {1538-9235},
support = {T35 EY07088/EY/NEI NIH HHS/United States ; P30 EY07551/EY/NEI NIH HHS/United States ; T35 EY07088/EY/NEI NIH HHS/United States ; P30 EY07551/EY/NEI NIH HHS/United States ; },
}
@article {pmid40423616,
year = {2025},
author = {Ollila, T and Joshi, A and Kulathinal, S and Immonen, I},
title = {Area Under the Curve Analysis in a Real-World Cohort of Finnish Patients Treated for Neovascular Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {5},
pages = {23},
pmid = {40423616},
issn = {2164-2591},
mesh = {Humans ; Male ; Female ; Aged ; *Visual Acuity/physiology ; *Area Under Curve ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Finland ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/physiopathology ; Aged, 80 and over ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Middle Aged ; Cohort Studies ; },
abstract = {PURPOSE: The purpose of this study was to explore the area under the curve (AUC) measures from visual acuity (VA) trajectories in describing outcomes for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: AUC analysis on 93 patients with nAMD was performed using VA trajectories up to 12&#xa0;months for the purpose of illustration. The broken stick model was first used to interpolate VA trajectories at prespecified times from uneven timepoints over the 4 year period. The AUC measures used were: general VA (AUCG; the area above 20 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), change from baseline (AUCI), and adjusted AUC (Adj AUC) to adjust the change from baseline with respect to the ceiling (85 letters) and the ground (20 letters). We studied how AUC ranking of outcomes differed from VA change from baseline and how AUC-derived parameters correlated with known prognostic factors, such as baseline VA, and optical coherence tomography findings at baseline and during treatment.<br><br>RESULTS: Median AUCIs in ascending quartiles of baseline VA were 88, 116, 38, and 10, respectively. The corresponding Adj AUCs were 0.12, 0.28, 0.13 and 0.29 (scale -1 to +1), suggesting a compensation for the ceiling effect. Median AUCIs in patients with baseline intraretinal, intraretinal + subretinal, or subretinal fluid were 40, 50, or 59, respectively. The corresponding Adj AUCIs were 0.14, 0.19, and 0.23, both showing the expected response to baseline fluid status.<br><br>CONCLUSIONS: Using the measures described here, modifiers of VA change and different anti-vascular endothelial growth factor (VEGF) treatment protocols can be compared from only one to three of the AUC values even in materials with uneven evaluation points.<br><br>TRANSLATIONAL RELEVANCE: AUC-based analysis provides new tools to evaluate the effectiveness of nAMD treatment.},
}
@article {pmid40423060,
year = {2025},
author = {Löw, K and Sitnilska, V and Tang, Y and Lammert, JQ and Krohne, TU and Altay, L},
title = {Real-Life Treatment Intervals and Morphological Outcomes Following the Switch to Faricimab Therapy in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of personalized medicine},
volume = {15},
number = {5},
pages = {},
pmid = {40423060},
issn = {2075-4426},
abstract = {Objectives: To evaluate the efficacy of faricimab in patients with neovascular age-related macular degeneration (nAMD) that did not respond to other VEGF inhibitors. Methods: This retrospective study included the eyes of patients diagnosed with nAMD who had been switched to faricimab treatment due to the persistence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), despite monthly anti-VEGF treatment with aflibercept, bevacizumab, or ranibizumab using the treat and extend regimen, and who had received at least three faricimab injections following the switch. Best-corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT) analysis were performed at each visit, and the OCT results were graded by two independent readers. Results: We included 41 eyes of 39 patients (21 male, 18 female) with a mean age of 80.5 ± 8.1 years. The median duration of anti-VEGF treatment prior to the switch to faricimab was 5.0 years, with a median of 53 injections. Complete resolution of IRF and SRF was observed after the first dose of faricimab in 12 eyes (29.3%) and after the third dose in 15 eyes (36.6%). Twenty-eight eyes reached a follow-up time after a switch of at least 12 months, with a median of 10 faricimab injections. Of these 28 eyes, 10 eyes (35.7%) exhibited complete IRF/SRF resolution; treatment intervals were extended beyond 4 weeks in 21 eyes (80.7%), and 8 eyes (28.6%) presented complete IRF/SRF resolution under extended treatment intervals at month 12. Central retinal thickness after 12 months was reduced from a median of 368.0 µm to 297.5 µm (p < 0.001), and the BCVA remained stable (p = 0.057). No adverse events were reported throughout the entire treatment period. Conclusions: In nAMD patients with poor anti-VEGF treatment response, complete and fast fluid resolution and the extension of treatment intervals can be reached by switching to faricimab, even after years of prior unsuccessful therapy.},
}
@article {pmid40419840,
year = {2025},
author = {Hu, W and Tu, Y and Tan, J and Lin, Y and Wang, Y and Zhou, Q},
title = {Global research trends on endoplasmic reticulum stress in retinal diseases from 2000 to 2024.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {210},
pmid = {40419840},
issn = {1573-2630},
support = {82260211 and 81460092//National Natural Science Foundation of China/ ; 20211ZDG02003//Central Government Guides Local Science and Technology Development Foundation/ ; 20203BBG73058 and 20192BBGL70033//Key research and development project in Jiangxi Province/ ; 2020A0166//Chinese medicine science and technology project in Jiangxi province/ ; },
mesh = {Humans ; *Retinal Diseases/metabolism ; *Endoplasmic Reticulum Stress/physiology ; *Biomedical Research/trends ; Bibliometrics ; },
abstract = {PURPOSE: To comprehensively explore global research trends on endoplasmic reticulum stress (ERS) in retinal diseases over the past 24 years.<br><br>METHODS: An analysis of 917 publications from the Web of Science Core Collection, spanning from 1 January 2000 to 15 April 2024, was conducted to explore ERS research in retinal diseases. Bibliometric and visualisation software was employed to identify key contributors and research trends.<br><br>RESULTS: Hideaki Hara and Sarah X. Zhang were identified as the most published and most cited authors, respectively. The United States led in both publications and citations. Sun Yat-sen University ranked highest in publications, while the University of Oklahoma received the most citations. Investigative Ophthalmology &amp; Visual Science was the leading journal in both publications and citations. A total of 108 of the 1385 author keywords, each occurring five or more times, clustered into four major themes: retinal photoreceptor degeneration, glaucoma and optic nerve damage, diabetic retinopathy and age-related macular degeneration. Keywords such as "in vivo", "dominant retinitis pigmentosa", "endothelial growth factor", "molecular", and "quality control" displayed the strongest citation bursts. ERS research (2000&#x2009;~&#x2009;2024) has evolved from retinal neuroprotection to include specific cell types and diseases, explored signalling pathways and therapeutic mechanisms, and more recently has focused on molecular insights and gene therapy applications.<br><br>CONCLUSION: This bibliometric analysis highlighted significant growth in publications on ERS in retinal diseases, reflecting an increasing scholarly focus. ERS represents a potential target for exploring pathological changes in retinal neuro-microvascular and related disorders, warranting further investigation.},
}
@article {pmid40419664,
year = {2025},
author = {Vats, A and Xi, Y and Wolf-Johnston, AS and Clinger, OD and Arbuckle, RK and Sheng, L and Jiang, X and Dermond, CD and Li, J and Stolz, DB and St Leger, AJ and Sahel, JA and Jackson, EK and Birder, LA and Chen, Y},
title = {Oral 8-aminoguanine against age-related retinal degeneration.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {812},
pmid = {40419664},
issn = {2399-3642},
support = {R01 AG056944/AG/NIA NIH HHS/United States ; R01 EY033049/EY/NEI NIH HHS/United States ; R01DK135076//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; R01 EY026891/EY/NEI NIH HHS/United States ; R01 DK135076/DK/NIDDK NIH HHS/United States ; R01 EY030991/EY/NEI NIH HHS/United States ; R01EY026891//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY032482/EY/NEI NIH HHS/United States ; R01EY032482//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01AG056944//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; Unrestricted grant//Research to Prevent Blindness (RPB)/ ; U01 EY034711/EY/NEI NIH HHS/United States ; R01EY030991//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; S10 RR019003/RR/NCRR NIH HHS/United States ; R01EY033049//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01HL109002//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; U01EY034711//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 CA256068/CA/NCI NIH HHS/United States ; P30EY08098//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; 1S10RR019003//U.S. Department of Health &amp; Human Services | NIH | National Center for Research Resources (NCRR)/ ; R01 HL109002/HL/NHLBI NIH HHS/United States ; Medical Student Eye Research Fellowship//Research to Prevent Blindness (RPB)/ ; P30 EY008098/EY/NEI NIH HHS/United States ; R01CA256068//U.S. Department of Health &amp; Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)/ ; },
mesh = {Animals ; Rats, Inbred F344 ; Administration, Oral ; *Guanine/analogs &amp; derivatives/administration &amp; dosage/pharmacology ; Rats ; *Retinal Degeneration/drug therapy/pathology ; Retina/drug effects/pathology ; *Aging/drug effects ; Male ; Disease Models, Animal ; Apoptosis/drug effects ; Oxidative Stress/drug effects ; },
abstract = {Vision decline in the elderly, often due to retinal aging, predisposes individuals to pathologies like age-related macular degeneration. Currently, there are few effective oral treatments for this condition. Our study introduces an oral agent, 8-aminoguanine (8-AG), which targets age-related retinal degeneration using an aged Fischer 344 rat model. When administered in drinking water at a low dose for 8 weeks starting at 22 months of age, 8-AG significantly preserves retinal structure and function, as evidenced by increased retinal thickness, enhanced photoreceptor integrity, and improved electroretinogram responses. 8-AG reduces apoptosis, oxidative damage, and microglial/macrophage activation in aging retinae. 8-AG also mitigates retinal inflammation at transcriptional and cytokine levels. Extending treatment to 17 weeks further amplifies these protective effects. Given its efficacy in various disease models, 8-AG shows great promise as an anti-aging compound with the potential to mitigate common hallmarks of aging.},
}
@article {pmid40419209,
year = {2025},
author = {Jones, A and Sun, A and Yang, H and Latuszek, A and Negron, N and Shi, P and Fury, W and Lehmann, GL and Hu, Y and Sagdullaev, B},
title = {Differential analysis of core complement components expression and localization across rodent, non-human primate, and human ocular tissues.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110433},
doi = {10.1016/j.exer.2025.110433},
pmid = {40419209},
issn = {1096-0007},
mesh = {Animals ; Humans ; *Complement C3/genetics/metabolism ; *Complement Factor H/metabolism/genetics ; *Choroid/metabolism ; *Retinal Pigment Epithelium/metabolism ; Disease Models, Animal ; Rats ; *Macular Degeneration/metabolism/genetics ; Mice ; Immunohistochemistry ; *Complement C5/genetics/metabolism ; *Complement System Proteins/genetics/metabolism ; Primates ; Macaca fascicularis ; *Gene Expression Regulation/physiology ; Macaca mulatta ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness. Genetic and pathophysiological studies have implicated that complement pathway dysfunction is a key contributor to progressive vision loss in AMD. Though the association between complement and AMD is recognized, numerous anti-complement therapeutics that had been tested in rodent model systems had limited success in clinical trials. Understanding complement factor production and site of action in ocular pathophysiology is critical for the development of efficacious therapeutics. However, our limited understanding of how these aspects of complement biology vary across species restricts our ability to predict clinical outcomes from studies using animal models. Here, we integrated transcriptomic and immunohistochemical assays to understand the expression and localization of core complement components (complement factor H (FH), complement 3 (C3), and complement 5 (C5)) between ocular tissues of rodent, non-human primate, and human species. We found that complement distribution varied significantly across the studied species, with the most striking differences observed in the FH. While rodents expressed Cfh, an alternative pathway inhibitor, mainly in the RPE, CFH expression in primate eyes was primarily confined to the choroid. These differences were consistent at the protein level, with rodent FH localized in the RPE and primate FH within the choriocapillaris, choroid and sclera. Regarding C5, a terminal complement pathway component, we observed minimal ocular mRNA levels in all three species. However, we observed detectable protein levels in the RPE in rodents and the choroid in humans. Next, C3 mRNA transcripts and C3 protein exhibited similar distribution in the choroid in both rodent and primate eyes. Together, our findings highlight key differences and similarities between rodent and primate complement biology that may offer insights into the translatability of animal models and inform the design of effective therapeutics.},
}
@article {pmid40417310,
year = {2025},
author = {Shi, D and Ning, Z and Zhang, Y and Guo, X and Wei, Y and Liu, M},
title = {Research Trends in Vascular Aging in the Last Decade: A Comprehensive Bibliometric Analysis.},
journal = {Vascular health and risk management},
volume = {21},
number = {},
pages = {411-423},
pmid = {40417310},
issn = {1178-2048},
mesh = {Humans ; Bibliometrics ; *Biomedical Research/trends ; *Aging/pathology/metabolism ; Time Factors ; Periodicals as Topic/trends ; Age Factors ; Animals ; *Blood Vessels/pathology/physiopathology/metabolism ; *Vascular Diseases/physiopathology/metabolism/pathology ; },
abstract = {BACKGROUND: In recent years, vascular aging has emerged as a hot topic in become an important direction of aging research, but a comprehensive bibliometric analysis has not been conducted.<br><br>METHODS: The Web of Science database was searched for articles and reviews on vascular aging from January 1, 2014, to August 20, 2024, and the literature was analyzed and knowledge maps were constructed using CiteSpace, VOSviewer, pajek and Scimago Graphica software for econometric analysis and knowledge graph construction of the literature.<br><br>RESULTS: A total of 38,910 authors from 7622 institutions in 111 countries published 7277 papers in 1344 academic journals, with a significant increase in publication volume. The United States is the country with the highest productivity and citation rates, and Mayo Clinic is the most active institution. Tarantini S published the most papers, while Csiszar A received the most citations. Retina-The Journal of Retinal and Vitreous Diseases journal published the most papers, and Circulation journal received the most citations. The main research aspects include age-related macular degeneration, arteriosclerosis, and oxidative stress, which are the main keywords in this field. In the last decade, the term c reactive protein has attracted great attention with its strongest citation explosion.<br><br>CONCLUSION: In the past decade, the research focus on vascular aging has been increasing year by year. Age-related macular degeneration, arteriosclerosis, oxidative stress and vascular endothelial cells are the emerging research directions in this field.},
}
@article {pmid40417263,
year = {2025},
author = {Marks, E and Anugu, A and Bisiani, J and Pentyala, S},
title = {Stem cell therapy as treatment for Stargardt disease.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414251320592},
pmid = {40417263},
issn = {2515-8414},
abstract = {Stargardt disease or Juvenile Macular Degeneration is a rare genetic disorder caused by a mutation in the ABCA4 gene that results in degeneration of the macula and loss of central vision. The mutation in the ABCA4 gene causes a build-up of lipofuscin, which is a substance that is left over from the breakdown and absorption of damaged blood cells. This build-up of lipofuscin causes the death of photoreceptor cells and the subsequent degeneration of the macula. Due to the nature of Stargardt's disease, there are currently no cures or treatment options. However, in recent years, there has been an increase in research and exploration of utilizing stem cell therapy as a potential cure and treatment for Stargardt disease. Growing research in the field of ophthalmology has found that the use of stem cells can potentially replace the loss of photoreceptor cells, slow the progression of the degeneration of vision, and be a potential new treatment option for Stargardt disease.},
}
@article {pmid40417242,
year = {2025},
author = {Arunachalam, T and Abraham, M and Orndahl, C and Menezes, S and Mukherjee, S and Duic, C and Prasad, M and Siddig, F and Bellur, S and Thavikulwat, AT and Bailey, C and Sadda, SR and Wong, WT and Chew, EY and Jeffrey, BG and Keenan, TDL},
title = {Longitudinal Analysis of Mesopic Microperimetry in a Phase II Trial Evaluating Minocycline for Geographic Atrophy.},
journal = {Ophthalmology science},
volume = {5},
number = {5},
pages = {100783},
pmid = {40417242},
issn = {2666-9145},
abstract = {PURPOSE: To analyze mesopic microperimetry data from a recent phase II trial of minocycline for geographic atrophy (GA) for possible efficacy on the change in visual function and, in the absence of efficacy, to perform longitudinal analyses as a natural history study.<br><br>DESIGN: Phase II, prospective, single-arm, nonrandomized trial. After a 9-month run-in phase, participants began oral minocycline 100&#xa0;mg twice daily for 3&#xa0;years.<br><br>PARTICIPANTS: Individuals with GA in &#x2265;1 eye.<br><br>METHODS: Participants underwent mesopic microperimetry at baseline, month 3, and every 6&#xa0;months thereafter, using a custom T-shaped test pattern. Rates of change in microperimetry parameters were compared between the 24-month treatment phase and 9-month run-in phase by linear spline regression.<br><br>MAIN OUTCOME MEASURES: The mean macular and responding sensitivity; the mean perilesional and extralesional sensitivity; number of absolute and relative scotomatous loci.<br><br>RESULTS: Thirty study eyes from 30 participants (mean age 74.1 years) underwent microperimetry (mean follow-up 27.4 months). For 5 of the 6 microperimetry parameters, no significant difference in the rate of change between the treatment and run-in phases was observed. The difference between the 2 phases was&#xa0;-0.74&#xa0;decibels (dB)/year (standard error [SE] 0.85; P&#xa0;=&#xa0;0.39) for mean macular sensitivity,&#xa0;-0.30&#xa0;dB/year (SE 0.85; P&#xa0;=&#xa0;0.72) for mean responding sensitivity, 1.23&#xa0;dB/year (SE 1.01; P&#xa0;=&#xa0;0.22) for mean perilesional sensitivity, and&#xa0;-0.02 (SE 0.01; P&#xa0;=&#xa0;0.31) for transformed mean extralesional sensitivity. The difference in incidence rate ratios between the 2 phases was 1.17 (SE 0.11; P&#xa0;=&#xa0;0.14) for absolute scotomatous loci and 0.73 (SE 0.11; P&#xa0;=&#xa0;0.004) for relative scotomatous loci.<br><br>CONCLUSIONS: The results do not appear consistent with a clinically meaningful effect of minocycline on the rate of visual function decline from GA progression. This is consistent with previous analyses of the corresponding structural data. The findings demonstrate the advantages and disadvantages of different microperimetry parameters. The optimal testing patterns and parameters represent a trade-off between greater sensitivity vs. greater risk of floor/ceiling effects, with regional averages providing a useful compromise. The results may provide insights to guide the development of microperimetry end points for clinical trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40414338,
year = {2025},
author = {Hussain, W and Jiang, ZL and Liu, Y and Wang, JY and Yasoob, TB and Hussain, SA and Laila, UE and Wu, DD and Ji, XY and Dang, YL},
title = {PEST-containing nuclear protein in eye health and disease: A review.},
journal = {Experimental eye research},
volume = {258},
number = {},
pages = {110451},
doi = {10.1016/j.exer.2025.110451},
pmid = {40414338},
issn = {1096-0007},
mesh = {Humans ; *Eye Diseases/metabolism/genetics ; *Nuclear Proteins/physiology/metabolism ; Animals ; },
abstract = {The human visual system plays a crucial role in how we perceive the world. However, it is susceptible to ocular conditions that can result in visual impairments. Globally, over 2.2 billion people suffer from vision impairments, including macular degeneration, refractive errors, cataracts, and glaucoma. In the field of iridology and ocular biology, essential proteins governing ocular homeostasis are frequently mutated or dysregulated. Clear vision is essential for people, and mutations related to these proteins can significantly impact the prevalence and progression of eye disorders. This review discusses proteins linked to ocular disorders, including the nuclear protein Ras, the human ER1 protein, and the PEST-containing nuclear protein (PCNP). Identifying and studying potential therapeutic targets and strategies to regulate these proteins is crucial for minimizing the burden of eye disorders. PCNP has been specifically linked to the development of several eye disorders. An understanding of these molecular processes will facilitate the development of clinical strategies to treat ocular disorders effectively. The main focus of this review is PCNP because of its significant role in the pathophysiology of eye disorders. Dysregulation of this protein has been linked to several ocular diseases, highlighting the need to clarify its functions. A comprehensive understanding of these essential proteins is vital for developing effective treatments and preventive measures against ocular pathologies. This review aims to advance global research, treatment, and management of preventable blindness and vision impairment by exploring strategies to target and regulate these potential therapeutic candidates.},
}
@article {pmid40412129,
year = {2025},
author = {Zhu, M and Wu, M and Yang, A and Tu, Y and Sun, C and Na, Y and Zhang, Y and Wang, Y and Su, H and Liu, X},
title = {(+)-a-Longipinene alleviates murine laser-induced choroidal neovascularization: Evidence from in vivo and in vitro experiments.},
journal = {International immunopharmacology},
volume = {159},
number = {},
pages = {114913},
doi = {10.1016/j.intimp.2025.114913},
pmid = {40412129},
issn = {1878-1705},
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/etiology/pathology ; Humans ; Mice ; *Endothelial Cells/drug effects ; Lasers/adverse effects ; Mice, Inbred C57BL ; Fibroblast Growth Factor 2/metabolism ; Male ; Cells, Cultured ; Disease Models, Animal ; Signal Transduction/drug effects ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Cell Proliferation/drug effects ; Cell Movement/drug effects ; Choroid/pathology/drug effects ; },
abstract = {Choroidal neovascularization (CNV) is a progressive, degenerative pathological change. CNV can lead to severe vision loss, even blindness. (+)-a-Longipinene (LON) is an essential oil isolated from Pinus koraiensis and Hypericum. It plays anti-inflammatory and anti-angiogenic roles. Here, we attempted to identify the role and mechanism of action of (+)-a-LON in a murine model of laser-induced CNV as well as in vitro in hypoxic human choroidal endothelial cells (HCECs). (+)-a-LON alleviated the formation of laser-induced CNV in mice without causing ocular and systemic toxicity. Moreover, (+)-a-LON inhibited the production of fibroblast growth factor 2 (FGF2) in hypoxic human HCECs by downregulating the M3 muscarinic acetylcholine receptor (M3 mAchR)/diacylglycerol (DAG)/protein kinase C alpha (PKCα)/E1A-binding protein P300 (EP300) pathway. Notably, (+)-a-LON inhibited the hypoxia-induced proliferation, migration, and tube formation of HCECs and also suppressed inflammatory responses in the cells by downregulating the M3 mAchR/DAG/PKCα/EP300/FGF2 pathway. Briefly, (+)-a-LON attenuated the symptoms of CNV possibly by blocking the M3 mAchR/DAG/PKCα/EP300/FGF2 pathway in CECs.},
}
@article {pmid40411685,
year = {2025},
author = {Peng, M and Zeng, Q and Zheng, W and Xia, X},
title = {Peripheral Choroid/RPE/Sclera as a Shared Pathogenic Hub: Multi-Tissue Transcriptomic Profiling Identifies Common Differentially Expressed Genes in Age-Related Macular Degeneration and Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {62},
number = {10},
pages = {12426-12444},
pmid = {40411685},
issn = {1559-1182},
support = {20200757//Research Program of Hunan Provincial Health Commission, China/ ; 2021JJ30397//the Hunan Natural Science Foundation Project, China/ ; 2020SK2119//the Hunan Provincial Science and Technology Department Focuses on Research and Development, China/ ; 81974134//National Natural Science Foundation of China/ ; 2020YFC2008205//National Key Research and Development Program of China/ ; },
mesh = {*Alzheimer Disease/genetics/pathology ; *Macular Degeneration/genetics/pathology ; *Gene Expression Profiling/methods ; Animals ; *Choroid/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; Protein Interaction Maps/genetics ; Humans ; *Transcriptome/genetics ; Gene Regulatory Networks ; Gene Expression Regulation ; Gene Ontology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) and Alzheimer's disease (AD), two prevalent neurodegenerative disorders, share overlapping pathophysiological features yet lack cross-disease therapeutic strategies. This study systematically investigates their parallel genes and shared molecular mechanisms to identify potential therapeutic targets for dry AMD, a condition with limited treatment options.<br><br>METHODS: Transcriptomic datasets for AMD (GSE155154) and AD (GSE95587) were retrieved from the GEO database. AMD tissues were stratified into four subgroups: macular retina (MR), macular choroid/RPE/sclera (MCRS), peripheral retina (PR), and peripheral choroid/RPE/sclera (PCRS). Common differentially expressed genes (DEGs) were identified and analyzed via functional enrichment (GO, KEGG), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks. Drug-gene interactions and competing endogenous RNA (ceRNA) networks were constructed to prioritize therapeutic targets. Key hub genes were experimentally validated in a sodium iodate-induced AMD murine model using RT-qPCR.<br><br>RESULTS: Comparative analysis revealed 89, 56, 4, and 130 common DEGs between AD and MR, MCRS, PR, and PCRS subgroups, respectively. Neuroactive ligand-receptor interactions were prioritized in MR/MCRS-AD analyses, while extracellular matrix organization emerged as the dominant pathway in PCRS-AD comparisons. GSEA identified conserved the TNF&#x3b1; signaling pathway via NF-&#x3ba;B across both diseases. PCRS exhibited consistent expression trends for shared genes and pathways with AD. Computational screening prioritized seven druggable targets (COL1A1, COL1A2, COL3A1, MMP2, MMP9, VCAN, ITGA5) with dual therapeutic potential, along with a reconstructed circRNA (circRNA_002179)-miRNA (miR-124)-mRNA (VCAN) regulatory axis. Experimental validation in a sodium iodate-induced AMD murine model confirmed region-specific dysregulation: hub genes were significantly downregulated in MCRS but upregulated in PCRS.<br><br>CONCLUSIONS: Our study delineates both convergent and divergent molecular landscapes of AMD and AD, with PCRS emerging as a critical locus for shared pathophysiology. These findings bridge a critical gap in understanding AMD-AD comorbidity, offering actionable strategies for targeted drug development.},
}
@article {pmid40411432,
year = {2025},
author = {Spooner, K and Broadhead, G and Fraser-Bell, S and Hong, T and Wong, JG and Chang, AA},
title = {Real-World 10-Year Outcomes of Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration: A Meta-Analysis.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {7},
pages = {773-790},
pmid = {40411432},
issn = {1442-9071},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Bevacizumab/therapeutic use ; Treatment Outcome ; Ranibizumab/therapeutic use ; },
abstract = {BACKGROUND: This study examines the long-term effectiveness of anti-VEGF therapy in managing neovascular age-related macular degeneration (nAMD). Despite the well-established short-term improvements of anti-VEGF therapy, there is limited data on its continued efficacy over extended periods. This meta-analysis synthesises real-world data to evaluate anti-VEGF therapy's long-term outcomes systematically.<br><br>METHODS: We conducted a comprehensive literature review across PubMed, EMBASE and Cochrane databases, focusing on studies that reported outcomes of anti-VEGF treatment for nAMD over a decade. The analysis included pooling baseline patient characteristics, study designs, sample sizes and changes in visual acuity (VA) over 10&#x2009;years.<br><br>RESULTS: Our search produced 12 observational studies encompassing 7509 eyes, with 1274 completing 10-years of follow-up. The most substantial improvement in VA was observed in the first year following the initiation of anti-VEGF therapy. On average, there was a decline of 8.11 letters in VA after 10&#x2009;years from baseline (95% CI -10.83 to -5.39, p&#x2009;<&#x2009;0.01). In some cases, VA reverted to baseline levels after 10&#x2009;years; in others, it declined significantly below baseline. Meta-regression showed that mean VA change was greater in those with a lower baseline VA and those treated with a higher number of injections over 10-years(p&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: Our findings suggest that the mean visual acuity of eyes treated for nAMD deteriorates progressively over the long-term from&#xa0;two&#x2009;years after starting treatment. Regular injections appear crucial for preserving maximum vision. While our analysis did not identify an increased incidence of serious ocular adverse events, the long-term impact of anti-VEGF therapy on geographic atrophy remains unclear and warrants further investigation.},
}
@article {pmid40410947,
year = {2025},
author = {Cleveland, SD and Baker, MJ and Erdman, AG and Nazari, H},
title = {Current and future directions for the use of handheld fundus cameras in telehealth.},
journal = {Expert review of medical devices},
volume = {22},
number = {7},
pages = {657-665},
doi = {10.1080/17434440.2025.2508877},
pmid = {40410947},
issn = {1745-2422},
mesh = {Humans ; *Telemedicine/instrumentation ; *Fundus Oculi ; Artificial Intelligence ; *Photography/instrumentation ; *Retinal Diseases/diagnosis/diagnostic imaging ; Machine Learning ; },
abstract = {INTRODUCTION: A shortage of trained retinal specialists has created a growing need for a telehealth retinal screening alternative. Recent developments in handheld fundus cameras, enhanced by artificial intelligence (AI) and machine learning (ML) methods, have created a promising avenue to satisfy the unmet need for efficient retinal disease screening. This paper discusses the state of current handheld fundus cameras as well as promising future directions.<br><br>AREAS COVERED: Commercially available handheld fundus cameras and the current and future developments in telehealth retinal screenings using these cameras are discussed. Relevant literature encompassing handheld fundus cameras, diagnostic accuracy, and AI in grading were included. Commercial handheld fundus cameras were targeted in the literature and from their company websites. Additional information was obtained through dialogs with company representatives.<br><br>EXPERT OPINION: Handheld fundus cameras utilized for telehealth retinal screening have shown success in multiple small-scale studies. To make their usage more widespread, multiple technical, technological, and methodical barriers must be addressed. This can be accomplished by improving the technology, utilizing AI, and developing telehealth guidelines.},
}
@article {pmid40409921,
year = {2025},
author = {Taylor, DJ and Enoch, J and Jones, L and Higgins, B and Binns, A and Crabb, DP},
title = {An overview of quality of life and visual outcomes in AMD.},
journal = {Progress in brain research},
volume = {292},
number = {},
pages = {203-229},
doi = {10.1016/bs.pbr.2025.03.007},
pmid = {40409921},
issn = {1875-7855},
mesh = {Humans ; *Quality of Life/psychology ; *Macular Degeneration/psychology/physiopathology/complications ; *Visual Acuity/physiology ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in high income countries and third most common cause of blindness worldwide. This chapter provides an overview of existing literature pertaining to the ways in which AMD impacts clinical measures of visual function, quality of life, and performance of everyday tasks. As well as being used in clinics, some of the tests described in this chapter have the potential to be piloted in patients' homes as self-monitoring tools, or as patient-centred outcome measures in clinical trials for new treatments in AMD. Moreover, the research findings reported in this literature review should help clinicians with patient management and expectations, and should to inform future patient, public and professional education on AMD.},
}
@article {pmid40409801,
year = {2025},
author = {García, DM},
title = {Retinal physiology in metabolic syndrome.},
journal = {Advances in genetics},
volume = {113},
number = {},
pages = {76-101},
doi = {10.1016/bs.adgen.2024.11.002},
pmid = {40409801},
issn = {0065-2660},
mesh = {Humans ; *Metabolic Syndrome/physiopathology/complications/metabolism/pathology ; *Retina/physiopathology/metabolism/pathology ; *Diabetic Retinopathy/physiopathology/pathology/metabolism ; *Obesity/complications/physiopathology/metabolism ; Oxidative Stress ; Insulin Resistance ; Animals ; Glaucoma ; },
abstract = {Obesity is increasingly recognized not only for its systemic health impacts but also for its association with visual defects and eye diseases. This chapter explores the relationship between obesity and ocular health, highlighting the mechanisms by which metabolic dysregulation influences visual outcomes. Obesity exacerbates risk factors such as hypertension, dyslipidemia, and insulin resistance, which compromise retinal and optic nerve health. Conditions like diabetic retinopathy, age-related macular degeneration, and glaucoma are discussed in the context of obesity-related inflammation, oxidative stress, and altered vascular function, focusing on the retina as one of the body's most metabolically demanding tissues. Key pathways include adipose-derived cytokines that disrupt retinal homeostasis, and the effects of insulin resistance on retinal cells and vasculature. Furthermore, this chapter covers emerging evidence on the advances of genetic factors linking diabetic retinopathy to retinal impairments. By elucidating these interactions, we aim to provide insight into preventive and therapeutic strategies that could mitigate vision loss among individuals with obesity.},
}
@article {pmid40409337,
year = {2025},
author = {Zhang, N and Ma, C and Shao, F and Wang, H and Ma, X},
title = {Fib@PEGDA/GelMA hydrogel as a light-curing thin-layer matrix for RPE cell growth and function.},
journal = {Biomedical materials (Bristol, England)},
volume = {20},
number = {4},
pages = {},
doi = {10.1088/1748-605X/addcab},
pmid = {40409337},
issn = {1748-605X},
mesh = {*Retinal Pigment Epithelium/cytology ; *Hydrogels/chemistry ; *Polyethylene Glycols/chemistry ; Humans ; Tissue Engineering/methods ; Cell Proliferation ; Cell Survival ; Biocompatible Materials/chemistry ; Tissue Scaffolds/chemistry ; Light ; Printing, Three-Dimensional ; Materials Testing ; Cell Line ; Animals ; },
abstract = {Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are leading causes of blindness globally, characterized by progressive degeneration of retinal pigment epithelium (RPE) and photoreceptor (PR) cells. Despite advancements, current therapies have not substantially arrested disease progression. Cell replacement therapy using healthy RPE and PR cells holds promise but faces obstacles such as poor cell survival, inadequate integration, and transplantation difficulties. To address these issues, tissue engineering combined with 3D printing has become a focal point. This study investigates the use of four hydrogels-GelMA, HAMA, AlgMA, and PEGDA-and their various crosslinked combinations for creating hydrogel thin-layer matrices conducive to RPE cell growth. PEGDA/GelMA hydrogel demonstrated optimal support for cell spreading and proliferation, which is not achievable with hydrogels matrices of other formulations. The relationship between the mechanical properties of PEGDA/GelMA hydrogels and cell growth was further refined. PEGDA600-20 hydrogel with a compressive modulus of 1245.07 ± 20.79 kPa was selected based on time-course viability assays, leading to the development of the optimized Fib@PEGDA/GelMA hydrogel exhibited exceptional biocompatibility. Compared to PEGDA/GelMA, CCK-8 assays demonstrated significantly improved relative cell viability at 24 h, 48 h, and 72 h, with increases of 17.73 ± 1.22%, 14.54 ± 3.63%, and 19.04 ± 2.31%, respectively on Fib@PEGDA/GelMA matrix. qRT-PCR results indicated a mitigation of epithelial-mesenchymal transition (EMT), as evidenced by downregulation of EMT markers (CDH2, COL1A1, and FN1), accompanied by reduced IL-6 levels. Fib@PEGDA/GelMA hydrogel enhanced phagocytic activity in ARPE-19 cells and promoted functional expression in hiPSC-RPEs. Additionally, the hydrogel showed favorablein vivobiocompatibility following subcutaneous implantation of RCS rats at 1, 2, and 4 weeks post-implantation evidenced by HE and Masson's staining. This system offers a promising bioink for 3D-printed retinal cell scaffolds and paves the way for future advancements in cell replacement therapies for retinal degenerative diseases.},
}
@article {pmid40407849,
year = {2025},
author = {Ridano, ME and Hanke-Gogokhia, C and Lehmann, GL and Caceres, PS and Vaglienti, MV and Ceschin, D and Schreiner, R and Croci, DO and Torroja-Fungairiño, C and Rodriguez-Boulan, E and Benedicto, I and Rabinovich, GA and Sánchez, MC},
title = {Stromal-Like Cells and Retinal Pigment Epithelium Modulate Choroidal Sprouting Through Galectin-1-Dependent and Independent Pathways.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {10},
pages = {e70671},
pmid = {40407849},
issn = {1530-6860},
support = {01586//agenciaidiar | Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica (FONCYT)/ ; 033805-I//MEC | Agencia Estatal de Investigaci&#xf3;n (AEI)/ ; 137111OA-I00//MEC | Agencia Estatal de Investigaci&#xf3;n (AEI)/ ; 1314//agenciaidiar | Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica (FONCYT)/ ; R01 EY08531//Foundation for the National Institutes of Health (FNIH)/ ; U54 CA221208/CA/NCI NIH HHS/United States ; 2440//agenciaidiar | Fondo para la Investigaci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica (FONCYT)/ ; },
mesh = {*Galectin 1/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/cytology ; Animals ; *Choroid/metabolism/blood supply ; Mice ; *Stromal Cells/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; Choroidal Neovascularization/metabolism ; Humans ; Macular Degeneration/metabolism ; },
abstract = {Outer retinal function depends on two supporting tissues: the retinal pigment epithelium (RPE) and the choroid. Limited molecular information is available on the intercellular networks that sustain RPE/choroid tissue in both healthy and pathological states. Galectin-1 (Gal1), a β-galactoside-binding lectin, has recently emerged as a key regulator of angiogenesis and a potential therapeutic target in vascular pathologies, including age-related macular degeneration. Here, we studied the expression of Gal1 in the outer retina and its regulatory role in the RPE/choroid under physiological and pathological conditions. Our findings indicate that Gal1 is predominantly associated with stromal cells in the RPE/choroid. In Gal1-deficient (Lgals1[-/-]) mice, the RPE/choroid ultrastructure and gene expression profiles were altered, and choroidal explants exhibited reduced sprouting compared to those of wild-type mice. Consistently, recombinant Gal1 promoted choroidal sprouting under hypoxic conditions, and stromal-like cells modulated pro-angiogenic and antiangiogenic gene expression in vitro under pathological conditions. Interestingly, Gal1 was also expressed by the RPE, with apical secretion under normoxia that shifted toward a basolateral phenotype under hypoxia. These findings identify stromal-like cells and RPE as key sources of Gal1 in the choroid, highlighting its distinct roles in maintaining RPE/choroid homeostasis in healthy or pathological microenvironments.},
}
@article {pmid40407556,
year = {2025},
author = {Udomwech, L and Eden, C and Tawanwongsri, W},
title = {Relationship Between Facial Melasma and Ocular Photoaging Diseases.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {40407556},
issn = {2076-3271},
mesh = {Humans ; *Melanosis/epidemiology/complications/etiology/pathology ; Female ; Middle Aged ; Aged ; Male ; Adult ; Cross-Sectional Studies ; Aged, 80 and over ; Ultraviolet Rays/adverse effects ; Face/pathology ; Thailand/epidemiology ; Sunlight/adverse effects ; *Eye Diseases/etiology/epidemiology ; Cataract/epidemiology/etiology ; },
abstract = {Background/Objectives: Facial melasma is a common, chronic, and relapsing hyperpigmentation disorder, affecting up to 40% of adult women in Southeast Asia. Although most cases are mild, the condition may have a considerable psychological impact. Ocular photoaging diseases are also common and have been increasingly recognized in aging populations exposed to chronic sunlight. Ultraviolet (UV) radiation is implicated in both melasma and ocular photoaging; however, their relationship remains unclear. Methods: This cross-sectional study investigated the association between facial melasma and UV-induced ocular conditions among 315 participants aged 30-80 years at Walailak University Hospital, Thailand. Facial melasma was diagnosed clinically and dermoscopically, with severity assessed using the modified Melasma Area Severity Index. Ophthalmological examinations evaluated UV-related ocular conditions, including pinguecula, pterygium, climatic droplet keratopathy, cataracts, and age-related macular degeneration. Logistic regression analyses were performed, adjusting for age, sex, and sun exposure. Results: Facial melasma was identified in 66.0% of participants (n = 208), and nuclear cataracts were significantly associated with melasma (adjusted odds ratio, 2.590; 95% confidence interval, 1.410-4.770; p = 0.002). Additionally, melasma severity correlated with nuclear cataract severity (ρ = 0.186, p = 0.001). Other ocular conditions were not significantly associated with melasma. Conclusions: These findings suggest a shared UV-related pathogenesis between facial melasma and nuclear cataracts. Sun protection measures, including regular sunscreen use, UV-blocking eyewear, and wide-brimmed hats, may help mitigate the risk of both conditions. Further multicenter studies are warranted to confirm these findings and explore the underlying mechanisms.},
}
@article {pmid40407506,
year = {2025},
author = {Poveda, JL and Arnáiz, P and López, S and Muñoz, B and Fernández-Ferreiro, A},
title = {Preferences of Hospital Pharmacists for the Different Attributes of Intravitreal Treatments for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Spain: The SEEKING Study.},
journal = {Pharmacy (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
pmid = {40407506},
issn = {2226-4787},
support = {//Roche Farma S.A./ ; },
abstract = {The process of evaluation and selection of drugs in Spain is currently changing, with hospital pharmacists (HPs) having a growing relevance. This cross-sectional observational study aimed to assess HPs' preferences for different hypothetical intravitreal treatments for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Best corrected visual acuity (BCVA), ocular adverse events (AE), annual drug cost, available presentation, and mechanisms of action (MoA) were the selected attributes. A conjoint analysis was used. Ninety-one HPs completed the study. The mean (SD) age was 39.2 (10.2) years, 60.4% were female, and the mean (SD) time of experience as HP was 12.6 (8.3) years. For nAMD treatments, BCVA (38.6%) and ocular AE (27.3%) were the most important attributes, while annual drug cost (16.3%), available presentation (11.1%), and MoA (6.7%) were not as important. For DME drugs, BCVA (44.6%) and ocular AE (25.5%) were the most significant factors; annual drug cost (17.9%), the drug's available presentation (7.3%), and MoA (4.8%) were not considered to be as crucial. Preferences were comparable independent of HP experience. Effectiveness and safety were the most important attributes when choosing a drug. Comprehending the significant characteristics for HPs could potentially improve their collaborative function within multidisciplinary teams involved in intravitreal treatments.},
}
@article {pmid40403167,
year = {2025},
author = {Marks, V and Golos, AM and Gill, M and Henick, D and Li, K and DeBroff, B and Kombo, N},
title = {Persistent Anterior Uveitis Following Cataract Surgery.},
journal = {Ocular immunology and inflammation},
volume = {33},
number = {8},
pages = {1618-1623},
doi = {10.1080/09273948.2025.2509716},
pmid = {40403167},
issn = {1744-5078},
mesh = {Humans ; Female ; Retrospective Studies ; *Uveitis, Anterior/epidemiology/etiology/diagnosis/drug therapy ; Male ; Aged ; Middle Aged ; Risk Factors ; Incidence ; *Cataract Extraction/adverse effects ; *Postoperative Complications ; Aged, 80 and over ; Visual Acuity ; Connecticut/epidemiology ; Follow-Up Studies ; Adult ; },
abstract = {PURPOSE: To determine the incidence of and risk factors for persistent anterior uveitis following cataract surgery.<br><br>METHODS: This was a retrospective cohort study of patients who underwent cataract surgery at a tertiary referral center in Connecticut, USA. Those with prior uveitis, complex ocular pathology, concurrent procedures, and surgical complications were excluded. The outcome was development of persistent anterior uveitis, defined as anterior chamber cell grade&#x2009;&#x2265;&#x2009;0.5+ and steroid treatment beyond two months. Patients who did and did not develop persistent anterior uveitis were compared using univariate and multivariate analysis.<br><br>RESULTS: Of 3341 patients (5419 eyes), 45 (61) developed persistent anterior uveitis (1.1% incidence). Cases were significantly younger (64.6&#x2009;years vs. 69.6&#x2009;years, p&#x2009;<&#x2009;0.001), and there were significantly higher proportions of female (73.8% compared to 58.5%, p&#x2009;=&#x2009;0.016) and Black or African American (54.1% vs. 15.5%, p&#x2009;<&#x2009;0.001) patients, as well as those with age-related macular degeneration (9.8% vs. 1.5%, p&#x2009;<&#x2009;0.001), previous intravitreal injections (14.8% vs. 6.0%, p&#x2009;=&#x2009;0.004), and diabetes (18.0% vs. 8.9%, p&#x2009;=&#x2009;0.013). In multivariate analysis, older age was associated with a significantly lower likelihood of persistent anterior uveitis (adjusted odds ratio (AOR)&#x2009;=&#x2009;0.963, 95% confidence interval (CI)=[0.942, 0.984]), whereas Black race (AOR&#x2009;=&#x2009;9.102, 95% CI&#x2009;=&#x2009;[4.836, 17.133]) and wet age-related macular degeneration (AOR&#x2009;=&#x2009;37.700, 95% CI&#x2009;=&#x2009;[6.408, 221.792]) were associated with a significantly higher likelihood.<br><br>CONCLUSIONS: In this study, 1.1% of eyes developed persistent anterior uveitis following cataract surgery. Younger age, Black race, and wet age-related macular degeneration should be investigated as potential risk factors to improve its prophylaxis, identification, and management.},
}
@article {pmid40402519,
year = {2025},
author = {Luo, T and Li, C and Zhou, L and Sun, H and Yang, MM},
title = {Protein Acetylation in Age-Related Macular Degeneration: Mechanisms, Roles, and Therapeutic Perspectives.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {5},
pages = {30},
pmid = {40402519},
issn = {1552-5783},
mesh = {Humans ; *Macular Degeneration/metabolism/drug therapy ; Acetylation ; Oxidative Stress/physiology ; Choroidal Neovascularization/metabolism ; Cellular Senescence/physiology ; },
abstract = {Age-related macular degeneration (AMD) is a top cause of severe vision loss and blindness in older adults globally. This multifactorial disease arises from genetic, environmental, and age-related factors. Protein acetylation modification plays a key role in AMD progression through both epigenetic and non-epigenetic pathways. This review comprehensively discusses the multidimensional impacts of protein acetylation in AMD, particularly its dynamic regulation of angiogenesis, oxidative stress, inflammatory responses, and cellular senescence. Recent evidence shows that histone acetylation modification inhibits choroidal neovascularization (CNV) formation by regulating vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF-1α) expression, while upregulating the complement inhibitor clusterin to maintain Bruch's membrane integrity. Additionally, the NAD+-dependent deacetylase SIRT1 modulates the deacetylation of transcription factors such as PGC-1α, NF-κB, and FOXO3, enhancing mitochondrial antioxidant function and suppressing inflammatory cascades to disrupt the vicious cycle of oxidative stress and chronic inflammation. In terms of cellular senescence, histone hypoacetylation and hyperacetylation of non-histone proteins (e.g., p53, E2F1) jointly cause retinal pigment epithelial (RPE) cell-cycle arrest and autophagy imbalance, accelerating AMD progression. Genetic evidence further reveals subtype-specific expression changes and epigenetic regulatory mechanisms of histone deacetylases (HDACs), such as HDAC11 and HDAC1/3, in AMD. This article explores the clinical significance of these findings and proposes a novel combined therapeutic strategy. It involves synergistically targeting acetylation homeostasis with HDAC inhibitors (e.g., TSA, AN7) and SIRT1 activators while inhibiting abnormal angiogenesis, repairing metabolic disorders, and restoring autophagy function. This dual-targeting approach may overcome current anti-VEGF therapy limitations and open new precision management avenues for AMD.},
}
@article {pmid40402186,
year = {2025},
author = {Schloesser, L and Ziemssen, F and Schuster, AK and Hasan, S and Finger, RP},
title = {[Screening recommendations for glaucoma, age-related macular degeneration and diabetic eye diseases].},
journal = {Die Ophthalmologie},
volume = {122},
number = {7},
pages = {518-523},
pmid = {40402186},
issn = {2731-7218},
mesh = {Humans ; *Glaucoma/diagnosis/epidemiology ; *Macular Degeneration/diagnosis/prevention &amp; control/epidemiology ; *Diabetic Retinopathy/diagnosis ; *Mass Screening/standards ; Germany ; *Practice Guidelines as Topic ; *Ophthalmology/standards ; },
abstract = {BACKGROUND: The main causes of blindness, age-related macular degeneration (AMD), glaucoma and diabetic eye diseases (DED), are becoming increasingly more important in terms of health economics due to the demographic developments.<br><br>OBJECTIVE: The current screening recommendations for these diseases and the underlying evidence are presented.<br><br>MATERIAL AND METHODS: A&#xa0;detailed literature search was conducted and the recommendations of the relevant guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) were summarized.<br><br>RESULTS: There are current screening recommendations for glaucoma and DED but there is still no consensus with respect to AMD. Screening for DED is financed by the statutory health insurance (SHI) and offered as part of routine care. Glaucoma screening is only covered by the SHI if certain risk factors are present and is not yet implemented across the board.<br><br>CONCLUSION: There are established screening programs for DED that are financed by the SHI; however, there are AWMF recommendations for glaucoma but no SHI-financed screening programs and there are still no AWMF screening recommendations for AMD. Whether and to what extent screening programs are used by the respective target populations should be further investigated in studies.},
}
@article {pmid40401519,
year = {2025},
author = {Gupta, R and Bunea, I and Alvisio, B and Barone, F and Gupta, R and Baker, D and Qian, H and Daniele, E and Contreary, CG and Montford, J and Sharma, R and Maminishkis, A and Singh, MS and Magone De Quadros Costa, MT and Kashani, AH and Amaral, J and Bharti, K},
title = {iPSC-RPE patch restores photoreceptors and regenerates choriocapillaris in a pig retinal degeneration model.},
journal = {JCI insight},
volume = {10},
number = {10},
pages = {},
pmid = {40401519},
issn = {2379-3708},
mesh = {Animals ; Swine ; *Induced Pluripotent Stem Cells/transplantation/cytology ; Disease Models, Animal ; *Retinal Pigment Epithelium/cytology/transplantation ; Tomography, Optical Coherence ; *Retinal Degeneration/therapy/pathology ; *Choroid ; Polylactic Acid-Polyglycolic Acid Copolymer ; Regeneration ; Tissue Scaffolds ; },
abstract = {Dry age-related macular degeneration (AMD) is a leading cause of untreatable vision loss. In advanced cases, retinal pigment epithelium (RPE) cell loss occurs alongside photoreceptor and choriocapillaris degeneration. We hypothesized that an RPE-patch would mitigate photoreceptor and choriocapillaris degeneration to restore vision. An induced pluripotent stem cell-derived RPE (iRPE) patch was developed using a clinically compatible manufacturing process by maturing iRPE cells on a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold. To compare outcomes, we developed a surgical procedure for immediate sequential delivery of PLGA-iRPE and/or PLGA-only patches in the subretinal space of a pig model of laser-induced outer retinal degeneration. Deep learning algorithm-based optical coherence tomography (OCT) image segmentation verified preservation of the photoreceptors over the areas of PLGA-iRPE-transplanted retina and not in laser-injured or PLGA-only-transplanted retina. Adaptive optics imaging of individual cone photoreceptors further supported this finding. OCT-angiography revealed choriocapillaris regeneration in PLGA-iRPE- and not in PLGA-only-transplanted retinas. Our data, obtained using clinically relevant techniques, verified that PLGA-iRPE supports photoreceptor survival and regenerates choriocapillaris in a laser-injured pig retina. Sequential delivery of two 8 mm2 transplants allows for testing of surgical feasibility and safety of the double dose. This work allows one surgery to treat larger and noncontiguous retinal degeneration areas.},
}
@article {pmid40400877,
year = {2025},
author = {Chujo, S and Matsubara, H and Mase, Y and Kato, K and Kondo, M},
title = {Successful Response to Intravitreal Faricimab Injections in a Case of Neovascular Age-Related Macular Degeneration in Vitrectomized Eyes.},
journal = {Cureus},
volume = {17},
number = {4},
pages = {e82709},
pmid = {40400877},
issn = {2168-8184},
abstract = {The half-life of anti-vascular endothelial growth factor (anti-VEGF) drugs shortens significantly after vitrectomy due to an increased intraocular pharmacokinetic clearance caused by the absence of the vitreous gel. This reduced half-life can limit the therapeutic effect of these intravitreal agents and complicate the management of conditions such as neovascular age-related macular degeneration (nAMD). We report a case of nAMD in a vitrectomized eye that showed inadequate response to both aflibercept and brolucizumab, but experienced effective suppression of exudation following intravitreal administration of faricimab. This case suggests that faricimab may offer a therapeutic benefit in managing exudative changes in vitrectomized eyes with nAMD.},
}
@article {pmid40398512,
year = {2025},
author = {Huang, A and Wu, Z and Ansari, G and Von Der Emde, L and Pfau, M and Schmitz-Valckenberg, S and Fleckenstein, M and Keenan, TDL and Sadda, SR and Guymer, RH and Cheung, CMG and Chakravarthy, U},
title = {Geographic atrophy: Understanding the relationship between structure and function.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {14},
number = {3},
pages = {100207},
pmid = {40398512},
issn = {2162-0989},
support = {ZIA EY000514/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Fluorescein Angiography/methods ; *Visual Fields/physiology ; Disease Progression ; Visual Field Tests ; },
abstract = {PURPOSE: This review explores the complex relationship between anatomical alterations and functional consequences in geographic atrophy (GA), the advanced non-neovascular form of age-related macular degeneration. We examine the natural history, progression patterns, structural biomarkers, functional assessments, and structure-function correlations in GA.<br><br>METHODS: Experts contributed specialized knowledge on GA pathophysiology, imaging biomarkers, and functional assessment methods. We synthesized an understanding of the relationship between structural changes (including fundus autofluorescence patterns, optical coherence tomography markers, and novel biomarkers) and functional outcomes (visual acuity, microperimetry, reading performance, and patient-reported outcomes), drawing from authors' research expertise and relevant literature.<br><br>RESULTS: While GA is defined by visible areas of outer retinal atrophy, the structure-function relationship is complex and often discordant. Visual acuity incompletely reflects the functional impact of GA, as it may remain preserved until foveal involvement occurs. Microperimetric assessments reveal functional deficits extending beyond visible atrophic borders, with varying degrees of correlation between structural and functional metrics. Different fundus autofluorescence patterns demonstrate distinct functional implications and progression rates. Recent innovations in imaging and visual function testing offer enhanced characterization of disease progression.<br><br>CONCLUSIONS: The complex relationship between structural and functional measures in GA reflects underlying pathophysiological mechanisms and has important implications for clinical trial endpoints and patient management. Multimodal assessment incorporating both structural and functional parameters is essential for the comprehensive evaluation and management of GA, particularly as novel therapeutic approaches emerge.},
}
@article {pmid40397942,
year = {2025},
author = {Osei Duah Junior, I and Akuffo, KO and Ampong, J and Owiredu, D and Boateng, BS and Danso-Appiah, A},
title = {Dietary factors and predominant eye diseases in sub-Saharan African populations: A systematic review protocol.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0320030},
pmid = {40397942},
issn = {1932-6203},
mesh = {Humans ; Systematic Reviews as Topic ; Africa South of the Sahara/epidemiology ; *Eye Diseases/epidemiology/etiology ; *Diet/adverse effects ; },
abstract = {Evidence linking diet and ocular diseases is growing, yet variations persist, with a paucity of data in sub-Saharan Africa. The proposed review will systematically synthesize evidence on dietary factors associated with predominant eye disorders (cataracts, refractive error, glaucoma, diabetic retinopathy, age-related macular degeneration, and dry eye disease) in the sub-Saharan African population. The systematic review protocol will follow PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) for transparency in reporting. All relevant published studies in the English Language will be identified from PubMed, Scopus, Web of Science, Embase, Health Inter-Network Access to Research Initiative (HINARI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), African Journal of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) using medical subject headings (MeSH) and controlled vocabulary without date restrictions. The reference lists of all retrieved studies will be checked and experts will be contacted for additional relevant studies. The risk of bias for observational studies will be assessed using ROBINS-E (Risk of Bias in Non-Randomized Studies - of Exposure) and for non-interventional and randomized studies ROBINS-V2 (Risk of Bias in Non-Randomized Studies version 2) and ROB2 (Cochrane Risk of Bias 2) will be employed respectively. Study quality will be assessed using the National Heart Lung and Blood Institutes Quality Assessment (NHLBI) tool for Observational Cohort and Cross-Sectional Studies and Controlled Interventional Studies. Meta-analysis will not be considered because of the wide range of dietary factors and the susceptibility to high heterogeneity. Patterns of association between dietary factors and the specific eye diseases will be consolidated by Synthesis Without Meta-analysis (SWiM).},
}
@article {pmid40397903,
year = {2025},
author = {Wang, P and Hu, Z and Haider, M and Hopman, W and Sharma, E and Sharma, S},
title = {The Association Between Hepatic Steatosis and Age-Related Macular Degeneration: A Cross-Sectional Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004526},
pmid = {40397903},
issn = {1539-2864},
abstract = {PURPOSE: The primary aim of this study is to estimate the association of hepatic steatosis in patients diagnosed with Age-Related Macular Degeneration (AMD).<br><br>METHODS: Patients with AMD and without secondary causes of chronic liver disease, alongside age- and sex-matched controls were recruited. Hepatic steatosis was determined via ultrasound imaging, and metabolic risk factors were collected using standardized surveys.<br><br>RESULTS: A total of 98 patients were recruited (49 cases, 49 controls). Hepatic steatosis was observed in 51.0% of the AMD group compared to 30.6% in controls, a statistically significant difference (&#x3c7;2(1) = 4.224, p = 0.040). In multivariable models, dyslipidemia and diabetes were the strongest predictors, with association of steatosis attenuated but still significant (OR 2.36, 95% CI 1.03-5.40, p = 0.049).<br><br>CONCLUSION: This study suggests an association between AMD and the prevalence of hepatic steatosis, after controlling for metabolic risk factors.},
}
@article {pmid40397174,
year = {2025},
author = {Heimes-Bussmann, B and Bellenbaum, R and Njoo, C and Liakopoulos, S and Schmitz-Valckenberg, S and Zortel, M and Rothaus, K and Leemhuis, J and Mussinghoff, P and Lommatzsch, A},
title = {[Faricimab in previously treated neovascular age-related macular degeneration : Study design of the prospective noninterventional study PASSENGER].},
journal = {Die Ophthalmologie},
volume = {122},
number = {9},
pages = {693-699},
pmid = {40397174},
issn = {2731-7218},
mesh = {Humans ; Prospective Studies ; *Wet Macular Degeneration/drug therapy ; Visual Acuity/drug effects ; Aged ; Middle Aged ; Male ; Female ; Quality of Life ; Treatment Outcome ; Germany ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: Faricimab was approved in the European Union in 9/2022 as the first bispecific antibody for the treatment of neovascular age-related macular degeneration (nAMD), visual impairment due to diabetic macular oedema (DME) or retinal vein occlusion. To date, the efficacy profile of faricimab has been investigated under pivotal clinical phase 3 study conditions in treatment-naïve nAMD patients. The prospective noninterventional study (NIS) PASSENGER is a multicentre study that aims at contributing to a better understanding of the effectiveness, safety and impact of faricimab on quality of life in previously treated patients with nAMD under real-world conditions in Germany.<br><br>METHODS: The planned observation period per patient is 24&#xa0;months. Patients (n&#x202f;=&#x2009;620) aged &#x2265;&#x202f;50&#xa0;years with nAMD who switched to faricimab no longer than 12&#xa0;weeks prior to enrolment in the study, were previously treated with a&#xa0;vascular endothelial growth factor (VEGF) inhibitor for a&#xa0;maximum of 36&#xa0;months, and had a&#xa0;best corrected visual acuity (BCVA) of 30-80 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale at the start of therapy with faricimab are eligible to participate. The primary outcome measure is the change in BCVA from baseline after 52&#xa0;weeks. In addition, central subfield thickness, intraretinal, subretinal and subpigment epithelial fluid over time as well as patient-reported outcomes, adherence and adverse events are recorded.<br><br>RESULT: The first patient was enrolled in June 2023. According to the current schedule, recruitment (24&#xa0;months) will be completed by June 2025 and the last patient visit is anticipated in Q2/2027.<br><br>CONCLUSION: Data from the PASSENGER study are intended to contribute to a&#xa0;better understanding of therapy management in daily practice in Germany.},
}
@article {pmid40396905,
year = {2025},
author = {Chen, Z and Zhu, X and Lu, MM and Ou, Q and Wang, X and Zhao, Z and Shen, Q and Wang, Q and Wang, Z and Xu, JY and Jin, C and Gao, F and Wang, J and Zhang, J and Zhang, J and Jin, X and Bi, Y and Lu, L and Xu, GT and Tian, H},
title = {PHOSPHO1 Suppresses Ferroptosis in Retinal Pigment Epithelial Cells by Reducing the Levels of Phosphatidylethanolamine Molecular Species.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {28},
pages = {e2505359},
pmid = {40396905},
issn = {2198-3844},
support = {2023YFC2506100//Ministry of Science and Technology of China/ ; 24ZR1470100//Natural Science Foundation of Shanghai/ ; 20234Y0113//Shanghai Municipal Health Commission/ ; 82471073//National Natural Science Foundation of China/ ; 82271108//National Natural Science Foundation of China/ ; },
mesh = {*Ferroptosis/physiology/genetics ; *Retinal Pigment Epithelium/metabolism ; *Phosphatidylethanolamines/metabolism ; Animals ; Rats ; Humans ; Lipid Peroxidation ; Macular Degeneration/metabolism ; Autophagy ; Epithelial Cells/metabolism ; *Phosphoric Monoester Hydrolases/metabolism/genetics ; Iron/metabolism ; Disease Models, Animal ; },
abstract = {Iron-induced lipid peroxidation of phosphatidylethanolamine (PE) species is a key driver of ferroptosis in retinal pigment epithelial (RPE) cells, a process closely associated with age-related macular degeneration (AMD). The previous studies have demonstrated that induced retinal pigment epithelial (iRPE) cells generated by transcription factor-mediated reprogramming exhibit superior therapeutic efficacy in treating AMD. In this study, it is found that these iRPE cells are resistant to ferroptosis and further identified phosphoethanolamine/phosphocholine phosphatase 1 (PHOSPHO1) as a critical regulator underlying ferroptosis resistance. Mechanistically, PHOSPHO1 inhibits ferroptosis through two distinct mechanisms. First, it reduces PE levels in the endoplasmic reticulum, thereby limiting PE-derived lipid peroxidation. Second, it suppresses autophagy and ferritinophagy, leading to a reduction in intracellular free iron accumulation. Experiments using an in vivo rat model confirm that PHOSPHO1 effectively protects RPE cells from ferroptotic damage. These findings highlight PHOSPHO1 as a potential therapeutic target for AMD, providing insights into novel ferroptosis-based intervention strategies.},
}
@article {pmid40396593,
year = {2025},
author = {Li, C and Wang, B},
title = {Role of P2X7R in Retinal Diseases: A Review.},
journal = {Immunity, inflammation and disease},
volume = {13},
number = {5},
pages = {e70203},
pmid = {40396593},
issn = {2050-4527},
support = {//This study was supported by the Natural Science Foundation of Gansu Province (22JR5RA971)./ ; },
mesh = {Humans ; *Receptors, Purinergic P2X7/metabolism ; Animals ; *Retinal Diseases/metabolism ; Macular Degeneration/metabolism ; Retinitis Pigmentosa/metabolism ; Diabetic Retinopathy/metabolism ; },
abstract = {BACKGROUND: P2X purinoceptor 7 receptor (P2X7R) is an ATP-gated ion channel that, upon activation by ATP, triggers the release of inflammatory mediators and induces apoptosis in cells. This channel plays a crucial role in the onset and progression of various diseases. Recently, there has been a growing body of research focused on the function of P2X7R receptors in ophthalmic conditions, particularly concerning retinal diseases such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa.<br><br>OBJECTIVE: This article is to provide a comprehensive review of the advancements in the study of P2X7R and its association with retinal diseases, elucidating its role in these conditions and identifying potential avenues for future research.<br><br>METHODS: Electronic databases, including PubMed, Web of Science, and Wan fang Data were searched for relevant literature. The following keywords were used: "P2X7R", Age-related macular degeneration", "Diabetic retinopathy", "Retinitis pigmentosa". Both preclinical and clinical studies were included to provide a holistic understanding of P2X7R's role in retinal pathology.<br><br>RESULTS: P2X7R activation exacerbates retinal diseases by promoting inflammation and apoptosis. However, its role in disease progression and homeostasis complicates therapeutic targeting, highlighting the need for selective inhibitors and further research into its context-dependent functions.<br><br>CONCLUSION: P2X7R plays a critical role in the pathogenesis of retinal diseases. At the same time, preclinical studies suggest that P2X7R inhibition holds promise as a therapeutic strategy. Future research should focus on developing selective P2X7R inhibitors, elucidating the receptor's role in different disease stages, and identifying biomarkers to guide personalized treatment. Addressing these challenges will be essential for translating P2X7R-targeted therapies into clinical practice and improving outcomes for patients with retinal diseases.},
}
@article {pmid40396232,
year = {2025},
author = {Chin, CH and Chien, CC and Huang, CJ and Ke, CY and Lee, YJ},
title = {Differential Transcription Factor Activator Protein-2 Delta Genotypes Affect the Levels of Interleukin-1 Beta, Interleukin 8, and Vascular Endothelial Growth Factor-C in the Retinal Pigment Epithelial Cells after Long-term Light Exposure.},
journal = {Journal of physiological investigation},
volume = {68},
number = {4},
pages = {218-228},
doi = {10.4103/ejpi.EJPI-D-24-00107},
pmid = {40396232},
issn = {2950-6344},
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/radiation effects ; Rats ; *Transcription Factor AP-2/genetics/metabolism ; *Interleukin-8/metabolism/genetics ; *Interleukin-1beta/metabolism/genetics ; Genotype ; Male ; *Light/adverse effects ; Rats, Sprague-Dawley ; },
abstract = {Retinal degeneration accompanied by abnormal neovascularization from the choroid in the macular area is a critical disease to cure. Retinal cell apoptosis or inflammation in the macula can lead to neovascularization in that area. Some environmental factors such as long-term light exposure, particularly the blue end of the light spectrum, can damage the retina, causing such a disease. Improved understanding of genetic molecules has indicated that certain genes may be potential biomarkers of neovascular macular degeneration. This study aimed to investigate the expression of transcription factor activator protein-2 δ (TFAP-2D) in the retina and explore its role in the pathogenesis of retinal degeneration. For this, a long-term light exposure animal model was used to evaluate TFAP-2D expression in the retina. In addition, two vectors overexpressing different genotypes of TFAP-2D were transfected into retinal pigment epithelial (RPE) cells, and the expression of angiogenesis molecules was investigated. It was found that TFAP-2D expression was observed in the RPE area of the retina in long-term light-exposed rats; however, no TFAP-2D expression was detected in the retina of control (normal) rats. Interleukins (ILs) 1B, IL8, vascular endothelial growth factor (VEGF)-C, and one VEGF receptor (kinase insert domain receptor) were significantly upregulated in RPE cells with TFAP-2D with a C allele at rs78648104 (TFAP-2D-C) overexpression. In conclusion, experiments with different TFAP-2D genotypes revealed that long-term light exposure upregulated TFAP-2D expression in the RPE cells of the retina. In addition, overexpression of TFAP-2D-C induced the release of IL1B, IL8, and VEGF-C, which may lead to neovascularization in the choroid and retina.},
}
@article {pmid40395179,
year = {2025},
author = {Zou, Y and Jiang, J and Li, Y and Ding, X and Tong, Q and Shi, Y and Xiao, L and Chen, L},
title = {Immune Checkpoint PD-L1 Modulates Retinal Microglial Activation to Alleviate Vascular Leakage in Choroidal Neovascularization via ERK.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {23},
pages = {e2400747},
pmid = {40395179},
issn = {2198-3844},
support = {81371042//National Natural Science Foundation of China/ ; 81870660//National Natural Science Foundation of China/ ; 22Y11910500//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; 202305AC160073//Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202401AY070001-172/174//Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; },
mesh = {Animals ; *Microglia/metabolism/immunology ; *B7-H1 Antigen/metabolism/genetics ; *Choroidal Neovascularization/metabolism/immunology ; Mice ; Disease Models, Animal ; *Retina/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; *Macular Degeneration/metabolism ; Humans ; MAP Kinase Signaling System ; },
abstract = {Neovascular age-related macular degeneration (NVAMD) is a common retinal disease causing vision loss in the elderly. Neuroinflammation significantly contributes to NVAMD's etiology. This study explores the role of Programmed cell death ligand 1 (PD-L1), an immune checkpoint (ICP) in microglia, known for limiting neuroinflammation in neurodegenerative diseases, and its potential function in NVAMD. This work finds increased PD-L1 expression in retinal microglia following laser injury. PD-L1 knockout (KO) or inhibitory PD-L1 antibody treatment worsens vascular leakage and neoangiogenesis in a laser-induced NVAMD mouse model, effects reversible by microglia depletion with PLX5622. This study underscores that choroidal neovascularization (CNV) may be regulated by multiple mechanisms, with PD-L1 modulation representing one of these pathways. Blocking PD-L1 elevated proinflammatory factors and p-ERK levels, indicating microglial overactivation in NVAMD. Conversely, enhancing PD-L1 signaling reduced neuroinflammation and neovascularization via ERK. These findings highlight PD-L1's role in neoangiogenesis and neuroinflammation in NVAMD, suggesting its potential as a target for immunomodulatory treatment in NVAMD.},
}
@article {pmid40394614,
year = {2025},
author = {Hushmandi, K and Lam, HY and Wong, WM and Tan, W and Daryabari, SH and Reiter, RJ and Farahani, N and Kumar, AP},
title = {Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.},
journal = {Cell communication and signaling : CCS},
volume = {23},
number = {1},
pages = {233},
pmid = {40394614},
issn = {1478-811X},
support = {NUHSRO/2023/039/RO5+6/Seed-Mar/04//National University of Singapore/ ; },
mesh = {Humans ; *Macular Degeneration/therapy/genetics ; *Genetic Therapy/methods ; Animals ; *Vision, Ocular ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of central vision loss, progressively impairing the retina and affecting millions worldwide. By 2040, global cases of AMD are projected to reach 300 million, posing a significant public health challenge. While early AMD may only cause mild visual impairment, advanced stages, particularly neovascular (wet) and non-neovascular (dry) AMD, can lead to severe vision loss or legal blindness, substantially affecting daily life. The introduction of anti-angiogenic therapies has revolutionized wet AMD treatment, offering a high probability of preserving or improving vision. However, these therapies do not halt AMD progression, and no definitive treatments exist for dry AMD. The limitations of current therapies, such as frequent injections and treatment resistance, underscore the urgent need for novel strategies. Gene therapy, which has shown success in treating other hereditary retinal diseases, offers a promising long-term solution for AMD by targeting retinal cells to produce therapeutic proteins. This review explores the potential of gene therapy for AMD, examining recent clinical trials and future treatment directions.},
}
@article {pmid40394320,
year = {2025},
author = {Masalkhi, M and Sporn, K and Kumar, R and Ong, J and Nguyen, T and Waisberg, E and Zaman, N and Lee, AG and Tavakkoli, A},
title = {Ophthalmic Image Synthesis and Analysis with Generative Adversarial Network Artificial Intelligence.},
journal = {Journal of imaging informatics in medicine},
volume = {},
number = {},
pages = {},
pmid = {40394320},
issn = {2948-2933},
abstract = {Generative adversarial networks (GANs), introduced by Ian Goodfellow in 2014, have revolutionized adversarial machine learning, particularly in data synthesis. This manuscript explores their application in ophthalmic diagnostics, addressing the scarcity of annotated datasets and the need for improved early disease detection. By leveraging GAN architectures, the goal is to enhance the quality of synthetic ophthalmic images, ultimately improving diagnostic algorithm training. A systematic review was conducted from January to April 2024 across PubMed, Embase, and Scopus. Search terms included "Generative Adversarial Networks" and "ophthalmic image synthesis." Articles were selected based on relevance to retinal image generation and diagnostic improvement in ophthalmology. GANs show considerable promise in generating high-resolution retinal and optical coherence tomography (OCT) images. Models like DR-GAN and Pix2Pix have successfully synthesized images that resemble real diagnostic data, proving valuable when annotated datasets are scarce. GAN-generated images enhance training for algorithms detecting diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent advances, including conditional GANs and CycleGANs, have enabled disease-specific image generation, boosting the diversity of training datasets, particularly in resource-limited settings. Integrating GANs into ophthalmic diagnostics represents a significant leap in medical AI, offering high-quality synthetic images to improve diagnostic algorithms. Despite their potential, challenges such as the need for larger datasets, improved image interpretability, and noise reduction must be addressed. Future research should focus on optimizing these models and incorporating multi-modal data to enhance diagnostic accuracy in clinical settings.},
}
@article {pmid40393567,
year = {2025},
author = {Zhang, J and Qian, Y and Shangguan, Y and Gong, Y and Shu, Y and Wang, Y},
title = {Bibliometric and visual analysis of retinal fibrosis research from 1993 to 2023.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {54},
number = {},
pages = {104636},
doi = {10.1016/j.pdpdt.2025.104636},
pmid = {40393567},
issn = {1873-1597},
mesh = {Humans ; *Bibliometrics ; Fibrosis ; *Retinal Diseases/pathology/diagnosis ; Tomography, Optical Coherence ; *Retina/pathology ; },
abstract = {BACKGROUND: Retinal fibrosis, a common pathological feature of various retinal diseases, significantly impairs vision. The mechanisms of retinal fibrosis are complex, with cytokine involvement playing a pivotal role. This article aims to elucidate the current research trends and key areas of focus in the study of retinal fibrosis.<br><br>METHODS: Publications from "Web of Science core collection", "PubMed" and "Scopus" were analyzed using R Studio ("Bibliometrix" and "ggplot2" packages) for publication counts, geographic distribution, and collaborations, while "CiteSpace" and "VOSviewer" visualized institutional partnerships and keyword co-occurrence. The methodology follows the PRISMA 2020 guidelines strictly.<br><br>RESULTS: In this analysis, a total of 1985 studies were analyzed. Key topics included "vitrectomy", "epiretinal membrane", "optical coherence tomography (OCT)", "macular membrane", and "macular hole". Keyword co-occurrence analysis emphased macular disease, fibrosis diagnosis, pharmacological treatment, and prognosis across various groups with cytokines as prominent research topics. Additionally, the findings suggested future research would focus on elucidating fibrosis mechanisms, advancing diagnostic techniques, and identifying potential drug targets. The journal "Retina" had the highest citation count for retinal fibrosis. The United States showed the greatest collaboration in retinal fibrosis research, particularly with China.<br><br>CONCLUSIONS: Current retinal fibrosis research focused on OCT diagnostics, cytokine mechanisms, and associated diseases such as diabetic retinopathy and macular degeneration. Future research will explore the integration of artificial intelligence in treatment strategies and the mechanisms underlying post-anti-vascular endothelial growth factor (VEGF) injection fibrosis.},
}
@article {pmid40391124,
year = {2025},
author = {Günter, A and Jarboui, MA and Mühlfriedel, R and Seeliger, MW},
title = {Exploration of the visual streak of the Mongolian gerbil as a model for the human central retina.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1562437},
pmid = {40391124},
issn = {2296-858X},
abstract = {INTRODUCTION: The Mongolian gerbil (MG), a day-active rodent, features a particular retinal region of high visual acuity, the visual streak (VS). Optimized for vision in desert-like environments, the VS allows for a perfect view of the horizon between the projection areas of the sky and the ground. Here, we assess the structural basis of this specialized region and compare the findings to the conditions at the human retinal center.<br><br>METHODS: The VSs of MG retinas (n&#x202f;=&#x202f;5) were evaluated morphologically with immunohistochemistry for cone, rod, and RPE cell-specific markers in dorsoventral cross-sections, and the results were compared to data from the near (adjacent) and far periphery. Mass spectrometry of the VS and peripheral retina/RPE was used to analyze the proteomic differential expression between these regions.<br><br>RESULTS: In the VS of the MG, we found an increased density of cones, elongated photoreceptor outer segments (OSs), and a rod-to-cone ratio lying within the zone of descent between the border of the macula and the fovea (macular shoulder). Similarly, the base area of retinal pigment epithelium (RPE) cells in the VS was significantly reduced, while cells were taller than those in the periphery. Accordingly, proteomic data provided evidence for an enhanced abundance of key proteins relevant to photoreceptor and RPE function and pathophysiology of macular diseases in the VS.<br><br>CONCLUSION: The high degree of conformance between the VS data of the MG and the human central retina renders the MG a promising rodent, non-primate model of the central human retina.},
}
@article {pmid40389215,
year = {2025},
author = {Lommatzsch, AP and Faatz, H},
title = {[Age-related macular degeneration - Part 2: therapeutic options for AMD].},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {8},
pages = {855-867},
doi = {10.1055/a-2515-9138},
pmid = {40389215},
issn = {1439-3999},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Degeneration/drug therapy/diagnosis ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Intravitreal Injections ; Evidence-Based Medicine ; },
abstract = {Currently, intravitreal anti-VEGF therapy is the only way to maintain function with continuous monitoring in neovascular AMD. Several robust morphological biomarkers, such as intraretinal and subretinal fluid, are important to guide treatment decisions at baseline and during the course of the disease. Higher concentrations of anti-VEGF agents and the development of bispecific antibodies combining anti-VEGF and anti-angiopoietin-2 antibodies have been shown to prolong the duration of action in pivotal trials. In particular, a longer duration of action may improve patient adherence by reducing the treatment burden. Several ranibizumab biosimilars are also approved and available for the treatment of neovascular AMD. In addition, bevacizumab is now approved in its originator form for the treatment of neovascular AMD in Europe. For the treatment of geographic atrophy, the intravitreal complement inhibitors approved in the US are not approved in Europe. With these drugs, continuous monthly or bimonthly injections were associated with significantly slower growth of the atrophic area in registration studies. Visual function after two years of treatment showed no difference compared to untreated eyes. In a post-hoc analysis of the largest supplementation studies AREDS and AREDS2, a significantly slower increase in RPE atrophy from the atrophic edge to the fovea was observed compared to placebo (AREDS [n = 208]: p = 0.012; AREDS2 [n = 392]: p = 0.011). This effect needs to be confirmed in controlled randomised trials.},
}
@article {pmid40388717,
year = {2025},
author = {Lishinsky-Fischer, N and Chowers, I and Levy, J},
title = {The effects of immunosuppressive therapy for immune-mediated inflammatory disease on the risk of age-related macular degeneration.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004531},
pmid = {40388717},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate the effects of immunosuppressive therapy on the development and progression of age-related macular degeneration (AMD) in patients with an immune-mediated inflammatory disease (IMID).<br><br>METHODS: This is a retrospective cohort study. Data were obtained from TriNetX, a global database of electronic medical records. The analysis utilized the largest network in TriNetX, comprised of 171,583,261 patients from 18 countries. Kaplan-Meier analysis was used to estimate the probability of predefined AMD subcategories between patients with IMID who were prescribed an immunosuppressants and patients who were not.<br><br>RESULTS: After 1:1 propensity score matching, equal-sized cohorts of patients in each group were generated for predefined IMIDs. We found that AMD was more prevalent in patients who received an immunosuppressant for systemic lupus erythematosus (SLE), Crohn's disease, rheumatoid arthritis, sarcoidosis, Sjogren's syndrome, giant cell arteritis and all IMIDs combined.<br><br>CONCLUSIONS: The use of immunosuppressants in patients with some IMIDs appears to be associated with an increased risk of AMD. Further research is warranted in order to fully understand the complex relationship between immunosuppressive therapy and AMD.},
}
@article {pmid40388106,
year = {2025},
author = {Sadda, S and Hatcher, KA and Shah, BK and Kondapalli, SS and Li, C and Baumal, CR},
title = {Outer Retinal Tubulation and Geographic Atrophy: A Natural History Analysis of Sham Observed Eyes from the OAKS and DERBY Trials.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {7},
pages = {1611-1619},
pmid = {40388106},
issn = {2193-8245},
abstract = {INTRODUCTION: Retrospective, longitudinal analysis of sham observed eyes from the phase 3 OAKS and DERBY trials evaluated the relationship between geographic atrophy (GA) growth and the presence or absence of outer retinal tubulation (ORT).<br><br>METHODS: Prevalence rates of ORT were calculated, and analysis of GA growth was performed using fundus autofluorescence and optical coherence tomography (OCT).<br><br>RESULTS: ORT prevalence rates were 32%, 37.5%, and 43% at baseline, month&#xa0;12, and month&#xa0;24, respectively. Eyes with a fully formed ORT at baseline had 23.6% less GA area growth over 24&#xa0;months compared with GA without ORT present at baseline.<br><br>CONCLUSION: The presence of ORT at baseline on OCT may be reflective of slower growth of GA, irrespective of GA location, as was noted in this series. The potential diagnostic impact of ORT should be considered when designing clinical studies for GA and when analyzing the results of such studies.<br><br>TRIAL REGISTRATION: OAKS: ClinicalTrials.gov identifier NCT03525613 (registered May&#xa0;15, 2018); EudraCT identifier 2018-001435-52 (registered September 27, 2018).<br><br>DERBY: ClinicalTrials.gov identifier NCT03525600 (registered May&#xa0;15, 2018); EudraCT identifier 2018-001436-22 (registered September 21, 2018).},
}
@article {pmid40386979,
year = {2025},
author = {Cheong, KX and Chi, M and Pan, W and Lee, YQ and Zhang, Y and Hu, Z and Htoon, HM and Hoang, QV and Chong, MF and Lan, W and Saw, SM and Lamoureux, EL},
title = {Diet and myopic macular degeneration in the Aier-SERI high myopia adult cohort study.},
journal = {Acta ophthalmologica},
volume = {103},
number = {8},
pages = {891-899},
doi = {10.1111/aos.17528},
pmid = {40386979},
issn = {1755-3768},
support = {JRDUKY004900//Duke-NUS Medical School Distinguished Professorship Fund/ ; 2024RC5002//Science and Technology Innovation Program of Hunan Province/ ; 2023RC1079//Science and Technology Innovation Program of Hunan Province/ ; },
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Prospective Studies ; Adult ; *Diet/adverse effects ; China/epidemiology ; Middle Aged ; *Myopia, Degenerative/epidemiology/complications/physiopathology/diagnosis ; *Refraction, Ocular/physiology ; *Macular Degeneration/epidemiology/etiology/diagnosis/physiopathology ; Follow-Up Studies ; Risk Factors ; *Feeding Behavior ; *Visual Acuity ; *Population Surveillance ; Surveys and Questionnaires ; },
abstract = {PURPOSE: We investigated relationships between two dietary composite scores and myopic macular degeneration (MMD) in a high myopia adult cohort, as there is a knowledge gap regarding the role of diet in MMD.<br><br>METHODS: This is a cross-sectional analysis of a population-based prospective cohort, the Aier-Singapore Eye Research Institute (SERI) high myopia cohort study of Chinese adults, in Changsha, central China. Systemic and ocular (including cycloplegic spherical equivalent [SE] and axial length [AL]) assessments were carried out. A self-administered food frequency questionnaire was used to assess the dietary intake. Dietary intake was categorised into 13 food groups (refined grains, whole grains, meat, fish, processed/unhealthy meat, plant-based protein, fruits, vegetables, fast food and savoury snacks, dairy products, desserts and sweet snacks, sugar-sweetened beverages, and alcohol). Using exploratory factor analysis, two dietary patterns (Dietary Pattern 1 [less healthy] and 2 [healthier]) were identified. Multivariable logistic regression analyses with Bonferroni corrections were performed to assess associations between diet and MMD.<br><br>RESULTS: Of 445 participants, 71 (16.0%) had MMD. The participants had an overall mean age of 42.3&#x2009;&#xb1;&#x2009;7.3&#x2009;years, SE of -9.5&#x2009;&#xb1;&#x2009;4.3 dioptres (D) and AL of 27.3&#x2009;&#xb1;&#x2009;11.86&#x2009;mm. In the multivariable analyses, none of the 13 food groups (p&#x2009;>&#x2009;0.004 for all) or 2 dietary patterns (p&#x2009;>&#x2009;0.05 for both) were associated with MMD, after adjusting for age, sex, education, SE and AL.<br><br>CONCLUSION: We did not find associations between diet and MMD in a cohort of highly myopic adults. There is currently no dietary advice to prevent MMD. Larger and prospective studies conducted over multiple time points are required.},
}
@article {pmid40386394,
year = {2025},
author = {Chiu, CJ and Chiu, E and Chang, ML},
title = {Interaction between Infection of Porphyromonas gingivalis, A Keystone Microbe of Oral Microbiome, and Serum Levels of Lutein/Zeaxanthin Is Associated with Risk for Age-related Macular Degeneration.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40386394},
issn = {2693-5015},
support = {R01 EY021826/EY/NEI NIH HHS/United States ; R21 EY028209/EY/NEI NIH HHS/United States ; },
abstract = {UNLABELLED: Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiome. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiome and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis. To investigate the potential association between periodontopathic microbiome and AMD occurrence, we conducted a candidate microbe approach case-control study. Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Aligning with the notion that the microbiome composition is significantly shaped by the host's diet, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 μmol/L or ≥ 20 μg/dL) might potentially mitigate the P. gingivalis-related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrition and oral microbiome, emphasizing their collective role in maintaining eye health.<br><br>SIGNIFICANCE STATEMENT: While our oral microbiome may impact eye health, nutritional factors could play a modulatory role in mitigating the associated risk.},
}
@article {pmid40385500,
year = {2025},
author = {Rajagopal, S and Ahuja, P and Quach, V and Luong, C and Raji, MA},
title = {Repurposing Alzheimer's disease medications-systemic cholinesterase inhibitors-for the treatment of dry eye syndrome, glaucoma, and age-related macular degeneration.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414251341022},
pmid = {40385500},
issn = {2515-8414},
}
@article {pmid40385108,
year = {2025},
author = {Yuan, LY and Li, LP and Hua, X and Yuan, XY},
title = {Tracing global progress: two decades of age-related macular degeneration research.},
journal = {International journal of ophthalmology},
volume = {18},
number = {5},
pages = {925-936},
pmid = {40385108},
issn = {2222-3959},
abstract = {AIM: To conduct a comprehensive bibliometric analysis of age-related macular degeneration (AMD) research from 2002 to 2022, identifying key contributing countries, institutions, authors, journals, and research hotspots to inform future research directions.<br><br>METHODS: Publications related to AMD were retrieved from the Web of Science Core Collection (WoSCC) database for the period January 1, 2002, to December 31, 2022. The search was limited to English-language articles and reviews. Bibliometric analysis was performed using Microsoft Excel 2021 for data management and annual publication analysis. Visualization and network analyses were conducted using VOSviewer, CiteSpace, and the Bibliometrix package in R. Collaboration networks among countries, institutions, authors, and journals were mapped. Keywords were analyzed for co-occurrence to identify research hotspots. Metrics such as H-index, total link strength (TLS), and citation counts were used to assess impact.<br><br>RESULTS: A total of 16 715 publications were analyzed, showing a consistent increase in AMD research output over the past 20y, peaking at 1445 publications in 2021. The United States was the leading contributor with 31.8% of total publications, followed by China and the United Kingdom. The University of Melbourne emerged as the most productive institution with the highest TLS, indicating strong international collaborations. Professor Frank G. Holz was identified as the most influential author based on H-index and publication count. Investigative Ophthalmology &amp; Visual Science was the most prolific journal and had the highest citation impact. Keyword co-occurrence analysis revealed four main research clusters: pathogenesis, therapy, epidemiology, and diagnosis. Emerging research hotspots included anti-vascular endothelial growth factor (VEGF) therapies, optical coherence tomography angiography, and artificial intelligence (AI) applications in diagnosis.<br><br>CONCLUSION: The bibliometric analysis highlights significant growth and collaborative efforts in AMD research globally. Key contributors have advanced understanding in pathogenesis, therapeutic strategies, epidemiology, and diagnostic technologies. Future research should focus on interdisciplinary collaborations, novel therapeutic targets, personalized medicine, and technological innovations such as AI to effectively address the challenges posed by AMD.},
}
@article {pmid40384191,
year = {2025},
author = {Borodi, PG and Slevin, M},
title = {Exploring the role of inflammation in age-related macular degeneration: new insights and implications for future therapies.},
journal = {Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie},
volume = {66},
number = {1},
pages = {51-59},
pmid = {40384191},
issn = {2066-8279},
mesh = {Humans ; *Macular Degeneration/therapy/pathology/complications ; *Inflammation/pathology/complications ; },
abstract = {The retina consists of one of the body's most delicate organs, being sensitive to various metabolic disturbances, vascular abnormalities and inflammatory processes. Age-related macular degeneration (AMD) impacts millions of people worldwide and represents a notable cause of blindness. Chronic inflammation, implicated in several degenerative diseases including Parkinson's and Alzheimer's diseases, as well as atherosclerosis, has been linked to AMD. Both histopathological and genetic investigations have underscored the immune system's role in AMD progression. The objective of this literature review was to summarize the actual knowledge, identify research gaps and to serve as a basis for future studies regarding the correlations between inflammation and AMD. We conducted a thorough search of the primary databases (Web of Science, Cochrane Library, PubMed/MEDLINE), using keywords such as 'age-related macular degeneration', 'inflammation', 'neurodegeneration', and 'C-reactive protein'. We included systematic reviews and meta-analyses that offer the most relevant results in this research area. We also included the results from recent studies that have not yet been widely approached. Our strategy also consisted of looking for relevant articles in the reference list.},
}
@article {pmid40383690,
year = {2025},
author = {Ko, MY and Talebi, R and Yu, F and Tseng, VL and Coleman, AL and Hosseini, H},
title = {Socioeconomic Disparities in Intravitreal Injection Use and Anti-VEGF Agent Selection: Aflibercept/Ranibizumab Versus Bevacizumab.},
journal = {Clinical therapeutics},
volume = {47},
number = {8},
pages = {559-565},
doi = {10.1016/j.clinthera.2025.04.010},
pmid = {40383690},
issn = {1879-114X},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use/economics ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Bevacizumab/administration &amp; dosage ; Intravitreal Injections ; Male ; Female ; Aged ; Cross-Sectional Studies ; Ranibizumab/administration &amp; dosage ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Socioeconomic Factors ; Diabetic Retinopathy/drug therapy ; United States ; *Healthcare Disparities/statistics &amp; numerical data/economics ; Macular Edema/drug therapy ; Retinal Vein Occlusion/drug therapy ; Databases, Factual ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Socioeconomic Disparities in Health ; },
abstract = {PURPOSE: There is a paucity of research on socioeconomic factors associated with intravitreal injection use or type of anti-vascular endothelial growth factor (anti-VEGF) use. The purpose of this cross-sectional analysis is to examine the association between demographic and socioeconomic factors and intravitreal injections and type of anti-VEGF (bevacizumab, aflibercept, and ranibizumab) use for patients with diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, and wet age-related macular degeneration in the AllofUs Database, which is a nationwide health database initiative conducted by the National Institutes of Health in the United States to enroll participants from groups that are considered to be historically underrepresented in biomedical research.<br><br>METHODS: The study population included patients diagnosed with diabetic macular edema, proliferative diabetic retinopathy, retinal vein occlusion, or wet age-related macular degeneration based on the International Classification of Diseases Ninth/10th Revision, Clinical Modification diagnosis codes. Exposures included age, sex, race/ethnicity, income, and education. Outcomes included IVI use based on the Current Procedural Terminology 4 codes and anti-VEGF type based on RxNorm codes.<br><br>FINDINGS: Of 3010 participants, 25.9% ever had IVI use. In multivariate logistic regression analyses, those with older age (adjusted odds ratio [aOR] = 1.27; 95% CI, 1.18-1.37) and income >$150,000 (aOR = 1.71; CI, 1.27-2.32) were more likely to have had IVI use. Those with older age (aOR = 1.46; CI, 1.22-1.75), Asian/other race/ethnicity (aOR = 3.81; CI, 1.09-13.34), Hispanic race/ethnicity (aOR = 3.16; CI, 1.59-6.26), income >$150,000 (aOR = 3.20; CI, 1.45-7.06), and college graduate/advanced degree (aOR = 1.83; CI, 1.01-3.31) were more likely to have aflibercept/ranibizumab only versus bevacizumab use.<br><br>IMPLICATIONS: Interventions are needed to increase health literacy and access to IVI for at-risk, low-income populations. Future research should investigate patient and provider decision-making for anti-VEGF drug choice, which may have implications for cost-saving measures and policies.},
}
@article {pmid40381862,
year = {2025},
author = {Chen, XN and Zhang, Y and Kam, KW and Au, SCL and Zhang, XJ and Ng, MPH and Yip, WW and Ip, P and Wong, ICK and Young, AL and Pang, CP and Tham, CC and Chen, LJ and Yam, JC},
title = {Genetic association of attention-deficit/hyperactivity disorder with thirteen ocular disorders.},
journal = {Journal of affective disorders},
volume = {385},
number = {},
pages = {119422},
doi = {10.1016/j.jad.2025.119422},
pmid = {40381862},
issn = {1573-2517},
mesh = {Humans ; *Attention Deficit Disorder with Hyperactivity/genetics/complications/epidemiology ; Mendelian Randomization Analysis ; *Eye Diseases/genetics/epidemiology ; Male ; Genetic Predisposition to Disease/genetics ; Female ; Linkage Disequilibrium/genetics ; Polymorphism, Single Nucleotide/genetics ; Child ; },
abstract = {PURPOSE: Although attention deficit hyperactivity disorder (ADHD) is linked to elevated risk of various ocular disorders, their genetic association and causality remain unclear.<br><br>METHODS: This study performed linkage disequilibrium score regression (LDSC) and pleiotropic analysis under composite null hypothesis (PLACO) to explore genetic associations, and bidirectional mendelian randomization (MR) to assess the causality between ADHD and thirteen ocular disorders.<br><br>RESULTS: LDSC showed ADHD genetically correlated with corneal ulcer, keratitis, blepharochalasis, lacrimal system disorders, senile cataract, retinal vascular occlusion, and age-related macular degeneration. MR revealed genetic liability to ADHD increased the risk of corneal ulcer (OR&#xa0;=&#xa0;1.18, FDR adjusted P&#xa0;=&#xa0;0.01), keratitis (OR&#xa0;=&#xa0;1.13, P&#xa0;=&#xa0;0.007), blepharochalasis (OR&#xa0;=&#xa0;1.23, P&#xa0;=&#xa0;0.002), and lacrimal system disorders (OR&#xa0;=&#xa0;1.09, P&#xa0;=&#xa0;0.04), while decreasing the risk of primary open-angle glaucoma (OR&#xa0;=&#xa0;0.83, P&#xa0;=&#xa0;0.003), exfoliation glaucoma (OR&#xa0;=&#xa0;0.71, P&#xa0;=&#xa0;0.001), and normotensive glaucoma (OR&#xa0;=&#xa0;0.79, P&#xa0;=&#xa0;0.02). Conversely, genetic liability to strabismus increased ADHD risk (OR&#xa0;=&#xa0;1.09, P&#xa0;=&#xa0;0.03). The identification of pleiotropic loci using PLACO suggested that genetic factors played a role in the associations between ADHD and ocular diseases.<br><br>CONCLUSIONS: This study revealed genetic associations between ADHD and multiple ocular disorders, identifying causal effects of ADHD on an increased risk of corneal ulcer, keratitis, blepharochalasis, and lacrimal system disorders, while showing a protective effect against glaucoma. Conversely, genetic liability to strabismus increased ADHD risk.},
}
@article {pmid40380672,
year = {2025},
author = {Feretzakis, G and Karakosta, C and Gkoulalas-Divanis, A and Bisoukis, A and Boufeas, IZ and Bazakidou, E and Sakagianni, A and Kalles, D and Verykios, VS},
title = {Leveraging Vision Transformers in Multimodal Models for Retinal OCT Analysis.},
journal = {Studies in health technology and informatics},
volume = {327},
number = {},
pages = {1135-1139},
doi = {10.3233/SHTI250567},
pmid = {40380672},
issn = {1879-8365},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Deep Learning ; Neural Networks, Computer ; *Retina/diagnostic imaging ; *Retinal Diseases/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging ; },
abstract = {Optical Coherence Tomography (OCT) has become an indispensable imaging modality in ophthalmology, providing high-resolution cross-sectional images of the retina. Accurate classification of OCT images is crucial for diagnosing retinal diseases such as Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME). This study explores the efficacy of various deep learning models, including convolutional neural networks (CNNs) and Vision Transformers (ViTs), in classifying OCT images. We also investigate the impact of integrating metadata (patient age, sex, eye laterality, and year) into the classification process, even when a significant portion of metadata is missing. Our results demonstrate that multimodal models leveraging both image and metadata inputs, such as the Multimodal ResNet18, can achieve competitive performance compared to image-only models, such as DenseNet121. Notably, DenseNet121 and Multimodal ResNet18 achieved the highest accuracy of 95.16%, with DenseNet121 showing a slightly higher F1-score of 0.9313. The multimodal ViT-based model also demonstrated promising results, achieving an accuracy of 93.22%, indicating the potential of Vision Transformers (ViTs) in medical image analysis, especially for handling complex multimodal data.},
}
@article {pmid40379450,
year = {2025},
author = {Mehta, NN and Nagel, ID and Agnihotri, A and Kalaw, FGP and Heinke, A and Cheng, L and Bartsch, DU and Freeman, WR},
title = {Anti-VEGF injections and macular atrophy progression in patients with neovascular age-related macular degeneration in remission.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {9},
pages = {1028-1035},
doi = {10.1136/bjo-2024-326124},
pmid = {40379450},
issn = {1468-2079},
support = {R01 EY033847/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Disease Progression ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Visual Acuity/physiology ; Fluorescein Angiography ; Bevacizumab/administration &amp; dosage ; *Macula Lutea/pathology ; Remission Induction ; Follow-Up Studies ; Middle Aged ; Atrophy ; },
abstract = {AIMS: To determine the effect of continuing anti-vascular endothelial growth factor (VEGF) injections on the progression of macular atrophy (MA) during remission of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: In this retrospective cohort study, 59 eyes with nAMD with at least 6-month remission (disease inactivity) were analysed and were grouped into two. In group 1, anti-VEGF injections were stopped after remission (holiday). In group 2, injections were continued despite inactivity (maintenance).Using blue autofluorescence images via Heidelberg Spectralis, MA area was measured at initial injection, remission onset and the latest available remission point. The absence of subretinal haemorrhage, intraretinal fluid, subretinal fluid or subretinal hyper-reflective material associated with fluid on serial spectral domain optical coherence tomography scans was used to confirm the inactivity of the disease (remission). The rate of progression of MA during the period of remission was measured for the two groups.<br><br>RESULTS: In group 1, 30 eyes received a mean of 16.97 injections over 39.2 months, followed by 21 months of drug holiday. In group 2, 29 eyes received a mean of 27.1 injections over 62.16 months, followed by a mean of 11.59 injections over 19.32 months for maintenance. The MA in the maintenance group progressed faster than the holiday group during remission (p=0.03).<br><br>CONCLUSIONS: Maintenance injections for nAMD in remission significantly increase progression of MA.},
}
@article {pmid40379195,
year = {2025},
author = {Zhang, P and Duan, J and Wang, C and Li, X and Su, J and Shang, Q},
title = {Predicting response to anti-VEGF therapy in neovascular age-related macular degeneration using random forest and SHAP algorithms.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {53},
number = {},
pages = {104635},
doi = {10.1016/j.pdpdt.2025.104635},
pmid = {40379195},
issn = {1873-1597},
mesh = {Humans ; Retrospective Studies ; Aged ; Tomography, Optical Coherence/methods ; Male ; Algorithms ; Female ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy/diagnostic imaging ; Machine Learning ; Aged, 80 and over ; Choroidal Neovascularization/drug therapy ; *Photochemotherapy/methods ; Middle Aged ; *Wet Macular Degeneration/drug therapy/diagnostic imaging ; Random Forest ; },
abstract = {PURPOSE: This study aimed to establish and validate a prediction model based on machine learning methods and SHAP algorithm to predict response to anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective study, we extracted data including demographic characteristics, laboratory test results, and imaging features from optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Eight machine learning methods, including Logistic Regression, Gradient Boosting Decision Tree, Random Forest, CatBoost, Support Vector Machine, XGboost, LightGBM, K Nearest Neighbors were employed to develop the predictive model. The machine learning method with optimal performance was selected for further interpretation. Finally, the SHAP algorithm was applied to explain the model's predictions.<br><br>RESULTS: The study included 145 patients with neovascular AMD. Among the eight models developed, the Random Forest model demonstrated general optimal performance, achieving a high accuracy of 75.86 % and the highest area under the receiver operating characteristic curve (AUC) value of 0.91. In this model, important features identified as significant contributors to the response to anti-VEGF therapy in neovascular AMD patients included fractal dimension, total number of end points, total number of junctions, total vessels length, vessels area, average lacunarity, choroidal neovascularization (CNV) type, age, duration and logMAR BCVA. SHAP analysis and visualization provided interpretation at both the factor level and individual level.<br><br>CONCLUSION: The Random Forest model for predicting response to anti-VEGF therapy in neovascular AMD using SHAP algorithm proved to be feasible and effective. OCTA imaging features, such as fractal dimension, total number of end points et al., were the most effective predictive factors.},
}
@article {pmid40376545,
year = {2025},
author = {Renton, AI and Klein, DJ and Livezey, JA and Nemrodov, D and Wolfer, S and Hanina, A and Van De Ville, D},
title = {Video-evoked neuromarkers of visual function in age-related macular degeneration.},
journal = {Frontiers in human neuroscience},
volume = {19},
number = {},
pages = {1569282},
pmid = {40376545},
issn = {1662-5161},
abstract = {Neural markers of visual function in age-related macular degeneration (AMD) allow clinicians and researchers to directly evaluate the functional changes in visual processing which occur as a result of the progressive loss of afferent input from the macula. Unfortunately, few protocols exist that elicit such neural markers, and most of these are poorly adapted to AMD. Here, we propose a novel method of embedding frequency tags into full color and motion videos by periodically manipulating the contrast of visual information of different spatial frequencies at different temporal frequencies. These videos elicit steady-state visual evoked potentials (SSVEPS) in viewers which, when measured using electrophysiological neuroimaging methods, independently represent the responses of populations of neurons tuned to the tagged spatial frequencies. We used electroencephalography (EEG) to record the SSVEPs of 15 AMD patients and 16 age-matched healthy controls watching a 6-min series of natural scene videos filtered with this spatial frequency tagging method. Compared with healthy controls, AMD patients showed a lower SSVEP to high spatial frequency information, and a stronger response to the low spatial frequency information in the video set. The ratio of the SSVEP to lower relative to higher spatial frequency information was strongly predictive of both visual acuity and contrast sensitivity, and the topographic distributions of these responses suggested retinotopic reorganization of the neural response to spatial frequency information.},
}
@article {pmid40374933,
year = {2025},
author = {Sadeghi, E and Schulman, A and Vupparaboina, SC and Singh, SR and Hasan, N and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J},
title = {Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {11},
pages = {2231-2237},
pmid = {40374933},
issn = {1476-5454},
mesh = {Humans ; Aged ; Male ; Female ; *Choroid/pathology/blood supply/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/pathology/physiopathology ; Fluorescein Angiography/methods ; *Retinal Vessels/pathology/diagnostic imaging ; Visual Acuity/physiology ; Severity of Illness Index ; Aged, 80 and over ; Middle Aged ; *Retina/pathology ; *Macular Degeneration/diagnosis/physiopathology ; Biomarkers ; Cross-Sectional Studies ; },
abstract = {PURPOSE: To assess retinal vascular perfusion and choroidal vascularity biomarkers correlated with drusen volume and severity of age-related macular degeneration (AMD).<br><br>METHODS: Patients underwent swept-source optical coherence tomography angiography (SS-OCTA) (PlexElite-9000). Eyes with geographic atrophy or neovascular AMD were excluded. Retinal thickness, retinal perfusion including superficial (SCP) and deep capillary plexuses (DCP), foveal avascular zone (FAZ), drusen volume, choroidal thickness (ChT) and choroidal vascularity index (CVI) were assessed through the Advanced Research and Innovation Network. Linear mixed model and Spearman test were used for statistical analysis.<br><br>RESULTS: We assessed 81 eyes from 57 subjects (34 early-stage, 47 intermediate-stage AMD). The mean age was 74.95&#x2009;&#xb1;&#x2009;8.79 years. The mean LogMar visual acuity (VA) was 0.16&#x2009;&#xb1;&#x2009;0.18 (early-stage:&#xa0;0.12&#x2009;&#xb1;&#x2009;0.17, intermediate-stage:&#xa0;0.19&#x2009;&#xb1;&#x2009;0.18, P&#x2009;=&#x2009;0.122). Between early and intermediate AMD, no significant differences were seen in SCP and DCP vascular perfusion (P&#x2009;=&#x2009;0.368, 0.859, respectively), FAZ (p&#x2009;=&#x2009;0.836) and retinal thickness within the 6-mm area (P&#x2009;=&#x2009;0.680). Drusen volume showed a significant difference (early-stage:&#xa0;0.0706&#x2009;&#xb1;&#x2009;0.1272, intermediate-stage:&#xa0;0.2102&#x2009;&#xb1;&#x2009;0.2211mm[3], P&#x2009;<&#x2009;0.01). Intermediate-stage AMD had significantly lower mean ChT (266.40&#x2009;&#xb1;&#x2009;115.55 vs. 204.97&#x2009;&#xb1;&#x2009;70.69&#x2009;&#xb5;m, P&#x2009;=&#x2009;0.038) and CVI (0.605&#x2009;&#xb1;&#x2009;0.021 vs. 0.591&#x2009;&#xb1;&#x2009;0.015, P&#x2009;=&#x2009;0.004) within the 5-mm area. Drusen volume was negatively correlated with ChT (r&#x2009;=&#x2009;-0.198, P&#x2009;=&#x2009;0.017) and CVI (r&#x2009;=&#x2009;-0.209, P&#x2009;=&#x2009;0.029). No significant correlation was found between drusen volume and VA (r&#x2009;=&#x2009;0.051, P&#x2009;=&#x2009;0.143), retinal thickness (-0.03, P&#x2009;=&#x2009;0.393), FAZ (r&#x2009;=&#x2009;-0.023, P&#x2009;=&#x2009;0.150), SCP (r&#x2009;=&#x2009;-0.011, P&#x2009;=&#x2009;0.307), and DCP (r&#x2009;=&#x2009;-0.022, P&#x2009;=&#x2009;0.190).<br><br>CONCLUSION: Drusen volume, a key AMD severity marker, correlates more strongly with choroidal parameters like ChT and CVI than retinal thickness and perfusion. It may serve as a biomarker for dry AMD severity, with choroidal biomarkers showing earlier disease changes.},
}
@article {pmid40374931,
year = {2025},
author = {Lim, JI and Ko, S and McAllister, M and Faux, N and Bawa, K and Mearns, E and Patel, S and Spicer, G and Martinez, A and Tabano, D},
title = {Systematic review of clinical practice guidelines for the management of neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {11},
pages = {2223-2230},
pmid = {40374931},
issn = {1476-5454},
support = {N/A//Genentech (Genentech, Inc.)/ ; },
mesh = {Humans ; *Practice Guidelines as Topic ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/diagnosis/therapy/drug therapy ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Disease Management ; },
abstract = {BACKGROUND/OBJECTIVES: To assess geographically global clinical practice guidelines (CPGs) for neovascular age-related macular degeneration (nAMD) management.<br><br>METHODS: A systematic literature review (SLR) of CPGs for nAMD management was conducted using Embase and MEDLINE databases, Guideline Central, Health Technology Assessment bodies, professional ophthalmology associations, and backwards citation tracking. CPGs published between January 2010-October 2023 were included and independently assessed by four reviewers using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). CPGs were qualitatively assessed for anatomical measurements (optical coherence tomography [OCT] and visual acuity [VA]). PROSPERO identification is CRD42023473223.<br><br>RESULTS: Nine of 147 identified global CPGs were included in the SLR for diagnosis, treatment, and disease monitoring for nAMD. Overall AGREE II scores were 62-95 (mean [standard deviation] score 75 [10.6]). Strongest domains were Scope and Purpose (86.6 [11.0]), Clarity of Presentation (84.3 [13.0]), and Editorial Independence (89.1 [15.4]); Stakeholder Involvement (63.4 [16.6]), Applicability (73.0 [12.6]), and Rigor of Development (55.4 [25.9]) were lowest. 4/9 CPGs were "Recommended" by reviewers, and 5/9 were "Recommended with Modifications". All CPGs recommended OCT for initial diagnosis. 2/9 CPGs did not mention VA. For managing pharmacological interventions, 4/9 CPGs recommended using VA, and three recommended OCT. Eight CPGs recommended using either VA or OCT for disease monitoring while on anti-vascular endothelial growth factor (VEGF) treatment. 6/9 CPGs recommended screening for VA and 7/9 CPGs recommended using OCT to change anti-VEGF intervals.<br><br>CONCLUSION: CPG methods, recommendations on applicability in resource-constrained systems, and patient advocacy/perspectives will improve CPG trustworthiness and transparency.},
}
@article {pmid40374798,
year = {2025},
author = {Shi, L},
title = {Enhancing medical explainability in deep learning for age-related macular degeneration diagnosis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {16975},
pmid = {40374798},
issn = {2045-2322},
mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Deep Learning ; },
abstract = {Deep learning models hold significant promise for disease diagnosis but often lack transparency in their decision-making processes, limiting trust and hindering clinical adoption. This study introduces a novel multi-task learning framework to enhance the medical explainability of deep learning models for diagnosing age-related macular degeneration (AMD) using fundus images. The framework simultaneously performs AMD classification and lesion segmentation, allowing the model to support its diagnoses with AMD-associated lesions identified through segmentation. In addition, we perform an in-depth interpretability analysis of the model, proposing the Medical Explainability Index (MXI), a novel metric that quantifies the medical relevance of the generated heatmaps by comparing them with the model's lesion segmentation output. This metric provides a measurable basis to evaluate whether the model's decisions are grounded in clinically meaningful information. The proposed method was trained and evaluated on the Automatic Detection Challenge on Age-Related Macular Degeneration (ADAM) dataset. Experimental results demonstrate robust performance, achieving an area under the curve (AUC) of 0.96 for classification and a Dice similarity coefficient (DSC) of 0.59 for segmentation, outperforming single-task models. By offering interpretable and clinically relevant insights, our approach aims to foster greater trust in AI-driven disease diagnosis and facilitate its adoption in clinical practice.},
}
@article {pmid40374738,
year = {2025},
author = {Wang, L and Wang, LX and Li, MY and Zhang, R and Zhou, GH},
title = {Clinical characterization of CCT2 and its role in autophagy regulation during age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {16849},
pmid = {40374738},
issn = {2045-2322},
support = {2022L203//Technology Innovation Project of Colleges and Universities in Shanxi Province/ ; No201903D321117//Major Research and Development Program of Shanxi/ ; No2020RC22//Medical major Research program of Shanxi/ ; No. 2020-195//Scientific Research Foundation for the Returned Overseas Chinese Scholars/ ; },
mesh = {Humans ; *Macular Degeneration/genetics/metabolism/pathology ; *Autophagy/genetics ; Male ; Female ; Aged ; *Chaperonin Containing TCP-1/genetics/metabolism ; Retina/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Transcriptome ; Gene Expression Profiling ; Middle Aged ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly, and the role of chaperonin containing TCP1 subunit 2 (CCT2) remains unclear. This study aims to elucidate the mechanistic link between CCT2 and AMD, contributing to improved understanding and potential therapeutic strategies. Retinal and RPE-Choroid transcriptome array data from 130 AMD patients and 121 normal donors (GSE29801 dataset) were reanalyzed to assess CCT2 expression across different AMD subtypes, age groups, and genders. Single-sample gene set enrichment analysis was performed to explore correlations with autophagy-related genes and other established AMD causes. Additionally, CCT2 expression was validated in sodium iodate (NaIO3)-induced 661 W cells (photoreceptor-like cells) using quantitative real-time PCR (qRT-PCR). CCT2 was significantly enriched in advanced AMD retinas compared to intermediate stages in retina (both macular and extramacular) and early stages in extramacular retina (p < 0.05). NaIO3-treated 661 W cells exhibited a similar expression trend, confirming transcriptomic findings. CCT2 is significantly upregulated in advanced AMD and may contribute to drusen degradation. It shows potential as both a biomarker and an independent diagnostic indicator, particularly for advanced-stage AMD.},
}
@article {pmid40374310,
year = {2025},
author = {Gouliopoulos, N and Bouratzis, N and Kympouropoulos, S and Datseris, I and Georgalas, I and Theodossiadis, P and Rouvas, A},
title = {Mental Health Consequences of Age-Related Macular Degeneration: Exploring Depression Prevalence and Severity in Wet and Dry Forms.},
journal = {Clinical gerontologist},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/07317115.2025.2506768},
pmid = {40374310},
issn = {1545-2301},
abstract = {OBJECTIVES: Age-related macular degeneration (AMD) is a leading cause of vision loss, affecting quality of life. Although AMD is associated with an increased risk of depression, differences between dry and wet forms are not well understood. This study examined depressive symptoms in Greek patients with dry and wet AMD compared to healthy-controls using the Zung Self-Rating Depression Scale (SDS).<br><br>METHODS: A cross-sectional study included 146 AMD patients (74 dry, 72 wet) and 60 controls. Depressive symptoms were assessed using the Zung SDS. Demographic and clinical data were collected. Statistical analyses compared depression severity and prevalence between groups, adjusting for potential confounders.<br><br>RESULTS: Wet AMD patients had significantly higher Zung SDS scores (50.4&#x2009;&#xb1;&#x2009;7.81) than dry AMD (44.8&#x2009;&#xb1;&#x2009;6.75) and controls (41.4&#x2009;&#xb1;&#x2009;7.85, p&#x2009;<&#x2009;.001). Depression prevalence was 56% in wet, 27% in dry AMD, and 20% in controls. After adjusting for visual acuity, age, sex, and other factors, wet AMD remained significantly associated with greater depression severity (p&#x2009;<&#x2009;.001).<br><br>CONCLUSIONS: Wet AMD is associated with higher depression severity compared to dry AMD, emphasizing the need for integrated ophthalmologic and mental health care.<br><br>CLINICAL IMPLICATIONS: Depression is common among AMD patients, particularly those with wet AMD. Screening and psychological support should be incorporated into AMD management.},
}
@article {pmid40374301,
year = {2025},
author = {Del-Cura, MP and Jimeno Anaya, L and Sastre Ibáñez, M and Quijada-Angeli, S and Martín-Herrero, A and Pastora-Salvador, N and Sánchez Marugán, B and Martínez Sánchez, M and Castaño Martín, B and Crespo-Carballés, MJ},
title = {Adherence and Awareness of Patients with Age-Related Macular Degeneration to AREDS 2 Recommended Nutritional Supplements.},
journal = {Journal of nutrition in gerontology and geriatrics},
volume = {44},
number = {2},
pages = {123-132},
doi = {10.1080/21551197.2025.2504911},
pmid = {40374301},
issn = {2155-1200},
mesh = {Humans ; Female ; *Dietary Supplements ; Male ; *Macular Degeneration ; Aged ; *Health Knowledge, Attitudes, Practice ; *Patient Compliance ; Middle Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Vitamins/therapeutic use/administration &amp; dosage ; Surveys and Questionnaires ; },
abstract = {BACKGROUND &amp; AIMS: Age-related macular degeneration (AMD) stands as the leading cause of visual impairment and blindness in developed nations. The Age-Related Eye Disease Study 2 (AREDS 2) conclusively demonstrated the advantages of vitamin and mineral supplementation in either preventing or slowing down the progression of AMD. This survey was crafted to evaluate the utilization of nutritional supplements and to gauge the knowledge, attitudes, and practices of patients with AMD. The aim was to identify factors predicting adherence and explore the public health implications.<br><br>METHODS: A cross-sectorial study was conducted involving 148 patients through a survey carried out at a tertiary-level hospital. The survey focused on patients with AMD who were candidates for nutritional supplements.<br><br>RESULTS: The primary outcome was the rate of adherence to AREDS recommendations, which was found to be 83%. Female gender (P&#x2009;=&#x2009;0.038), effective medication regimen management (P&#x2009;<&#x2009;0.01), and higher levels of education (P&#x2009;<&#x2009;0.01) emerged as independent factors significantly associated with adherence.<br><br>CONCLUSIONS: While ophthalmologists play a crucial role in addressing neovascular complications of AMD, they also bear the responsibility of promoting patient adherence to AREDS supplements. Achieving optimal compliance requires addressing the multifaceted factors identified in this study, with specific attention to patients' educational backgrounds and informational requirements.},
}
@article {pmid40373839,
year = {2025},
author = {Zou, R and Wu, X and Chen, H and Yuan, F and Yuan, Y},
title = {CLK2-SOX3 combination promotes choroidal neovascularization by SGLT1 inducing endothelial cell metabolic reprogramming.},
journal = {Cellular signalling},
volume = {133},
number = {},
pages = {111865},
doi = {10.1016/j.cellsig.2025.111865},
pmid = {40373839},
issn = {1873-3913},
mesh = {Animals ; *Endothelial Cells/metabolism ; Mice ; *SOXB1 Transcription Factors/metabolism/genetics ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Sodium-Glucose Transporter 1/metabolism/genetics ; *Protein Serine-Threonine Kinases/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; Cellular Reprogramming ; Metabolic Reprogramming ; },
abstract = {Choroidal neovascularization (CNV) is one of the main causes of visual loss. Endothelial cell metabolic reprogramming is an important mechanism in regulating pathological neovascularization. However, how endothelial cell metabolic reprogramming is regulated in CNV is not yet clear. In this study, we constructed CNV mouse model by laser injury and in vitro cell model by hypoxia-induced mouse brain microvascular endothelial cells (BMECs). We identified glucose transporter Sodium-Dependent Glucose Transporter 1 (SGLT1) regulating endothelial cell metabolic reprogramming by siRNA transfection and metabolomics analysis. Mechanistically, we manifested the TCTTTGTCTG and ATTGCCTC sequences in the sglt1 promoter was targeted by SRY-box transcription factor 3 (SOX3). Furtherly, the function of SOX3 was induced by its Ser97 site combining with CDC-like kinase 2 (CLK2). Our results show that the CLK2-SOX3 combination targets sglt1, thereby inducing metabolic reprogramming of endothelial cells and promoting CNV.},
}
@article {pmid40373229,
year = {2025},
author = {Ong, C and Sun, C and Mathur, R and Chan, CM and Yeo, I and Sim, S and Teo, K and Cheung, G},
title = {Fundus Autofluorescence (FAF) Alteration in Polypoidal Choroidal Vasculopathy (PCV) and Typical Neovascular Age Related Macular Degeneration (tAMD).},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {9},
pages = {1727-1737},
pmid = {40373229},
issn = {1539-2864},
abstract = {PURPOSE: To characterize and evaluate differences in fundus autofluorescence (FAF) alteration in polypoidal choroidal vasculopathy (PCV) and typical neovascular age related macular degeneration (tAMD).<br><br>METHODS: We used multimodal imaging to delineate the area of macular neovascularization (MNV) and extent of subretinal fluid (SRF). Macular FAF alteration was categorized to those limited to the area of the neovascular lesion (zone 1), area beyond zone 1 affected by subretinal fluid or pigment epithelial detachment (zone 2), and area beyond zone 2 (zone 3). Loss of FAF signal that correlated with complete outer retina and RPE loss (c-RORA) was documented.<br><br>RESULTS: We included 94 eyes from 94 patients (48 with diagnosis of PCV; 46 with diagnosis of tAMD). PCV eyes had greater subfoveal choroidal thickness (250 &#xb1; 92 &#x3bc;m vs 178 &#xb1; 86 &#x3bc;m, p<0.001) compared to tAMD. FAF alteration was seen in all eyes in Zone 1 and 2. Polypoidal lesion(s) appear as hyper-AF, iso-AF or hypo-AF round lesions. FAF alteration extending to zone 3 was observed in 41.7% of PCV eyes and 19.6% of tAMD eyes (p=0.02), in which hyper-AF pattern was predominant. Furthermore, zone 3 FAF alteration was associated with choroidal vascular hyperpermeability in eyes with PCV but not in tAMD (40% vs 0%, p=0.03).<br><br>CONCLUSION: These findings highlight RPE dysfunction may affect widespread areas in PCV, and may be the effect of choroidal congestion.},
}
@article {pmid40372516,
year = {2025},
author = {Zimmermann, ME and Thanner, V and Helbig, H and Stark, KJ and Heid, IM and Brandl, C},
title = {[Awareness for age-related macular degeneration in the population-based AugUR study : Comparison of participant self-report with medical records data from treating ophthalmologists].},
journal = {Die Ophthalmologie},
volume = {122},
number = {8},
pages = {612-618},
pmid = {40372516},
issn = {2731-7218},
support = {01ER1206//BMBF/ ; 01ER1507//BMBF/ ; HE3690/7-1//DFG/ ; HE3690/5-1//DFG/ ; BR 6028/2-1//DFG/ ; R01 EY RES 511967/GF/NIH HHS/United States ; R01 EY RES 516564/GF/NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Macular Degeneration/epidemiology/diagnosis/psychology ; *Self Report ; Male ; Female ; Aged, 80 and over ; *Ophthalmologists/statistics &amp; numerical data ; Germany/epidemiology ; *Medical Records/statistics &amp; numerical data ; *Health Knowledge, Attitudes, Practice ; Awareness ; },
abstract = {BACKGROUND: Limited awareness of existing age-related macular degeneration (AMD) can negatively affect the use of appropriate healthcare. This is particularly true for the older population, who are most commonly affected by AMD.<br><br>OBJECTIVES: Analyzing the awareness of an existing AMD diagnosis in the older population. We evaluated AMD self-reports of participants of the population-based AugUR study aged &#x2265;&#x202f;70&#xa0;years in and around Regensburg using the records of treating ophthalmologists (BAA).<br><br>MATERIALS AND METHODS: AMD self-reports of the AugUR participants were collected at study inclusion using interview-based questionnaires. An AMD diagnosis documented by the BAA was recorded by the BAA using an online questionnaire. Consensus or dissent of the available information was determined by creating a&#xa0;timeline for the date of study inclusion, the date of the first documented AMD diagnosis by the BAA and the date of the last visit to the BAA.<br><br>RESULTS: Self-report and BAA records on AMD were available for 1473 AugUR participants. Consensus was reached for 1270 individuals (86%). Of the 262 individuals with an existing BAA AMD diagnosis prior to study inclusion, 166 (63%) reported that they did not have AMD. In 137 of these 166 "underreporters", early stages of AMD were documented by the BAA.<br><br>CONCLUSION: Our results suggest that 63% of the older population with a&#xa0;BAA-AMD diagnosis are unaware of their AMD diagnosis. Most of these diagnoses represent early stages of AMD, which may not be communicated to patients as "AMD". Improved awareness, including early forms of AMD, could support preventative behavior by those affected.},
}
@article {pmid40372291,
year = {2025},
author = {, and , },
title = {Prevalence of Vision Loss in High-Income Countries and in Eastern and Central Europe in 2020: Magnitude and Temporal Trends.},
journal = {Ophthalmic epidemiology},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/09286586.2025.2486461},
pmid = {40372291},
issn = {1744-5086},
abstract = {PURPOSE: To estimate the prevalence of vision loss for 2020 in high-income countries (HICs) and Central/Eastern Europe and analyse evolving trends since 1990.<br><br>METHODS: Based on a systematic review of medical literature, prevalence of blindness, moderate and severe vision impairment (MSVI), mild vision impairment (VI), moderate VI and presbyopia were estimated for 1990, 2000, 2010, and 2020.<br><br>RESULTS: The study included 68 population-based studies. In the whole study region, the age-standardized prevalence (all ages) of blindness, MSVI, moderate VI, severe VI, mild VI, and presbyopia-related VI was 0.17% (95% CI:0.15-0.19), 2.27% (2.05-2.49), 2.06% (1.84-2.29), 0.21% (0.18-0.23), 1.79% (1.62-1.99), and 2.61% (1.88-3.48) respectively, with slightly higher rates for women than men. The prevalence rates were higher in Central/Eastern Europe than in the HIC, and lower than the global rates. Stratified between Australasia, high-income Asia Pacific region, high-income North America, Western Europe, Central Europe, and Eastern Europe, the age-standardized prevalence of blindness changed between 2000 and 2020 for men aged 50+&#xa0;years by -7.95% (-8.11/-7.78), -14.51% (-14.64/-14.38), +13.18% (+13.00/+13.36), -12.07% (-12.23/-11.91), -14.39% (-14.54/-14.23), and -23.59% (-23.72/-23.46), respectively, without significant sex-related differences. Highest increase was in high-income North America (+13.18% (+13.00/+13.36)) and most marked reduction in Eastern Europe (-23.59% (-23.72/-23.46)). Estimated blind individuals were stratified as follows: Australasia, 68,866 (54,913-84,527), high-income Asia Pacific region, 535,124 (439,912-640,330), high-income North America, 711,990 (575,977-867,402), Western Europe, 1,533,752 (1,218,371-1,898,343), Central Europe, 327,352 (264,513-398,083) and Eastern Europe, 789,618 (663,130-923,121).<br><br>CONCLUSIONS: Age-standardized prevalence of blindness and MSVI have further decreased in HIC and Eastern/Central Europe (except for high-income North America with an increase).},
}
@article {pmid40371972,
year = {2025},
author = {Goldberg, RA and Boyer, DS and Holz, FG and MacCumber, MW and Garg, SJ and Brown, DM and Lad, EM and Steinle, N and Rishi, PS and Pearce, I and Ach, T and Ribeiro, R and Li, C and Jones, D and Tsuboi, M and Ferrone, PJ and Baumal, CR and Wykoff, CC},
title = {Pegcetacoplan for Geographic Atrophy Over 30 Months: Data From OAKS, DERBY, and the GALE Long-Term Extension Study.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {7},
pages = {398-406},
doi = {10.3928/23258160-20250217-01},
pmid = {40371972},
issn = {2325-8179},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; *Geographic Atrophy/diagnosis/drug therapy/etiology ; Intravitreal Injections ; Time Factors ; Tomography, Optical Coherence/methods ; Treatment Outcome ; *Visual Acuity ; },
abstract = {BACKGROUND AND OBJECTIVE: This study will report safety and efficacy of pegcetacoplan for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>PATIENTS AND METHODS: GALE is a phase 3, open-label, multicenter, 36-month extension of the OAKS and DERBY studies. Patients who received pegcetacoplan monthly (PM) or every other month (PEOM) in OAKS or DERBY continued the same regimen in GALE (PM-PM and PEOM-PEOM); sham-observed patients initiated pegcetacoplan, maintaining the same interval.<br><br>RESULTS: In the first 6 months of GALE, 3.0% of study eyes developed exudative AMD, 1.3% intraocular inflammation, 0.1% ischemic optic neuropathy, and none endophthalmitis. Pegcetacoplan reduced GA growth rate by 39% (PM-PM) and 32% (PEOM-PEOM), with increasing efficacy over time across GA subtypes. In eyes with nonsubfoveal GA, pegcetacoplan reduced GA growth rate by 45% (PM-PM) and 33% (PEOM-PEOM).<br><br>CONCLUSION: Pegcetacoplan reduced GA growth rate up to 45% with increasing efficacy over 30 months and demonstrated a favorable safety profile. [Ophthalmic Surg Lasers Imaging Retina 2025;56:398-406.].},
}
@article {pmid40371970,
year = {2025},
author = {Ali, FS and Tabano, DC and Borkar, DS and Leng, T and Garmo, V and Ahmed, A and Myers, R and Shaia, JK and Barteselli, G and Singh, RP},
title = {Early Outcomes After Initiation of Faricimab for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {8},
pages = {468-477},
doi = {10.3928/23258160-20250304-02},
pmid = {40371970},
issn = {2325-8179},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Aged, 80 and over ; Tomography, Optical Coherence ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Middle Aged ; Time Factors ; Antibodies, Bispecific ; },
abstract = {BACKGROUND AND OBJECTIVE: This study assessed treatment patterns and early outcomes among patients with neovascular age-related macular degeneration (nAMD) initiating faricimab in routine clinical practice in the United States.<br><br>PATIENTS AND METHODS: FARETINA-AMD is a retrospective study among patients with nAMD initiating faricimab from February 2022 to June 2023 identified from the US IRIS[&#xae;] Registry.<br><br>RESULTS: Included were 21,508 patients previously treated with anti-vascular endothelial growth factor (anti-VEGF) (25,784 eyes) and 1,836 treatment-na&#xef;ve patients (1,982 eyes) with nAMD. Among previously treated eyes, visual acuity remained stable with faricimab. In treatment-na&#xef;ve eyes, mean &#xb1; SD visual acuity improved from 56.7 &#xb1; 24.1 letters at index to 61.4 &#xb1; 22.3 after faricimab injection 4 (P < 0.01). Mean &#xb1; SD central subfield thickness improved from 315.2 &#xb1; 80.0 (index) to 264.9 &#xb1; 60.1 &#x3bc;m (injection 4) in treatment-na&#xef;ve eyes and 296.2 &#xb1; 95.5 to 273.0 &#xb1; 81.4 &#x3bc;m in previously treated eyes (both P < 0.01).<br><br>CONCLUSIONS: Among patients with nAMD receiving faricimab, visual acuity improved in treatment-na&#xef;ve eyes, and both previously treated and treatment-na&#xef;ve eyes experienced anatomical improvement.},
}
@article {pmid40365784,
year = {2025},
author = {Oertel, J and Fischer, D and Tarhan, M and Meller, D and Hammer, M},
title = {Fundus autofluorescence lifetimes in age-related macular degeneration versus healthy controls in a pseudophakic population.},
journal = {Acta ophthalmologica},
volume = {103},
number = {6},
pages = {e394-e400},
pmid = {40365784},
issn = {1755-3768},
support = {HA 4430/5-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Pseudophakia/complications/diagnosis ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Ophthalmoscopy/methods ; Fundus Oculi ; *Macular Degeneration/diagnosis ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Retrospective Studies ; },
abstract = {PURPOSE: To check whether prolonged fundus autofluorescence (FAF) lifetimes in age-related macular degeneration (AMD) could be an artefact resulting from lens fluorescence.<br><br>METHODS: Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in pseudophakic intermediate AMD as well as healthy controls. The median values of FAF lifetimes in the centre, the inner and the outer ring of the ETDRS grid, obtained as amplitude-weighted mean of the lifetimes from a three-exponential fit of the fluorescence decay over time in two spectral channels, as well as peak emission wavelengths (PEW) were compared between patients and controls. The age dependence of FAF lifetime was checked per group. In the patient cohort, FAF lifetimes of individuals with and without subretinal drusenoid deposits (SDD) were compared.<br><br>RESULTS: Forty-four AMD patients (mean age 80.0&#x2009;&#xb1;&#x2009;6.0&#x2009;years) and 26 controls (mean age 73.0&#x2009;&#xb1;&#x2009;10.2&#x2009;years) were included. The FAF lifetimes of a subgroup of patients (N&#x2009;=&#x2009;25, mean age 76.3&#x2009;&#xb1;&#x2009;5.6&#x2009;years), age-matched to the controls, were significantly longer than those of the controls (all grid areas and spectral channels p&#x2009;<&#x2009;0.001). FAF lifetimes increased with age in the controls (p&#x2009;=&#x2009;0.006-0.03), but not in the patients. Patients with SDD had longer FAF lifetimes than those without (p&#x2009;=&#x2009;0.003-0.068). PEW neither showed significant group differences nor age dependence.<br><br>CONCLUSIONS: Although long fluorescence lifetimes of the lens can affect FAF lifetime measurements, prolonged FAF lifetimes in AMD are specific to the disease and not a lens artefact as shown in pseudophakic eyes. The effect of AMD on the lifetimes outweighs that of age. Patients with SDD, who have a higher risk of AMD progression, also show longer FAF lifetimes.},
}
@article {pmid40365539,
year = {2025},
author = {Xiaodong, L and Xia, C and Xuewei, Q and Dandan, W and Yi, Y and Zhilin, L},
title = {Sustainable Practices in Anti-VEGF Therapy: A 15-Year Bibliometric Analysis of Ranibizumab for Age-Related Macular Degeneration.},
journal = {Journal of ophthalmology},
volume = {2025},
number = {},
pages = {8891531},
pmid = {40365539},
issn = {2090-004X},
abstract = {Objective: A bibliometric analysis was performed in the domain of ranibizumab and age-related macular degeneration (AMD) to delineate current trends in international research dynamics and to provide a visual representation of research hotspots and challenges associated with ophthalmic drugs over the past 15 years. This study also evaluates the sustainability of ranibizumab therapy through reduced injection burden, cost-effectiveness compared to alternative treatments, and long-term outcomes that minimize healthcare resource utilization. Method: In this cross-sectional study, bibliometrics analyzed data retrieved and extracted from the Web of Science Core Collection (WOSCC) database to analyze the evolution and thematic trends in the delivery of studies from January 1, 2008, to September 2, 2023, for ranibizumab and AMD studies. A total of 2691 articles on the field were assessed for specific characteristics such as the year of publication, journal, author, institution, country/region, citation, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed using VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. Results: From 2008 to 2023, the cumulative number of articles published globally increased from 1 to 2,691, with the highest number of articles published in 2020 (255 papers). RETINA THE JOURNAL OF RETINAL AND VITREOUS DISEASES published the most manuscripts (285 papers) and was cited (6496 citations), followed by OPHTHALMOLOGY (193 papers) and GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY (163 papers). OPHTHALMOLOGY was the most cited (20,865 citations), with the United States (786 papers, 38,014 citations), Univ Sydney (98 papers, 5245 citations), and Kim, Jong Woo (56 papers, 550 citations) being the most productive and influential institutions, countries, and authors, respectively. Five clusters were formed by summarizing the top 100 keywords, which marked the emerging frontier of ranibizumab and AMD-related research. Further discussion of the five clusters of research is to assist the researcher in determining the scope of the research topic and planning the direction of the research. Conclusion: Over the past two decades, there has been a notable increase in the number of publications and citations pertaining to ranibizumab and AMD across various countries, institutions, and authors. This study elucidates current trends, global collaboration patterns, foundational knowledge, research hotspots, and developmental trajectories within the realm of ranibizumab-related AMD research. Key advancements in AMD treatment with ranibizumab over the last 15 years have centered on less frequent injection schedules, extended drug efficacy, and enhanced safety profiles.},
}
@article {pmid40364630,
year = {2026},
author = {de Lima-Vasconcellos, TH and Bovi Dos Santos, G and Móvio, MI and Donnici, GK and Badin, GM and de Araujo, DR and Kihara, AH},
title = {Neuroprotection provided by polyphenols and flavonoids in photoreceptor degenerative diseases.},
journal = {Neural regeneration research},
volume = {21},
number = {3},
pages = {908-922},
pmid = {40364630},
issn = {1673-5374},
abstract = {The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches. Photoreceptor degeneration, the common endpoint in various retinal diseases, including retinitis pigmentosa and age-related macular degeneration, leads to vision loss or blindness. While primary cell death is driven by genetic mutations, oxidative stress, and neuroinflammation, additional mechanisms contribute to disease progression. In retinitis pigmentosa, a multitude of genetic alterations can trigger the degeneration of photoreceptors, while other retinopathies, such as age-related macular degeneration, are initiated by combinations of environmental factors, such as diet, smoking, and hypertension, with genetic predispositions. Nutraceutical therapies, which blend the principles of nutrition and pharmaceuticals, aim to harness the health benefits of bioactive compounds for therapeutic applications. These compounds generally possess multi-target effects. Polyphenols and flavonoids, secondary plant metabolites abundant in plant-based foods, are known for their antioxidant, neuroprotective, and anti-inflammatory properties. This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa. Furthermore, the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed. By combining nutraceuticals with other emerging therapies, such as genetic and cell-based treatments, it is possible to offer a more comprehensive approach to treating retinal degenerative diseases. These advancements could lead to a viable and accessible option, improving the quality of life for patients with retinal diseases.},
}
@article {pmid40364275,
year = {2025},
author = {Saito, M and Mitamura, M and Ito, Y and Endo, H and Katsuta, S and Ishida, S},
title = {Inter-Relationships Between the Deep Learning-Based Pachychoroid Index and Clinical Features Associated with Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364275},
issn = {2077-0383},
abstract = {Background/Objectives: To investigate the impact of pachychoroid on the clinical features of neovascular age-related macular degeneration (nAMD) in Japan using the deep learning-based Hokkaido University pachychoroid index (HUPI), which has a high discriminative ability for pachychoroid. Methods: This retrospective observational study examined 124 eyes of 111 treatment-naïve nAMD patients, including 44 eyes with type 1 macular neovascularization (MNV), 26 eyes with type 2 MNV, and 54 eyes with polypoidal choroidal vasculopathy (PCV). HUPI was calculated for each eye from EDI-OCT choroidal images using our modified LeNet that had learned the image patterns of pachychoroid. Differences in HUPI between nAMD types and inter-relationships between nAMD parameters, including HUPI, were evaluated. Results: The mean HUPI was 0.53 ± 0.30 for type 1 MNV, 0.33 ± 0.23 for type 2 MNV, and 0.61 ± 0.3 for PCV, with significant differences between any two of the three groups (p < 0.05, for each). Round-robin multiple regression analysis for nAMD parameters showed the close associations of the HUPI with choroidal vascular hyperpermeability (CVH) and subretinal fluid (SRF) (p = 0.017 and p < 0.001 for each) and the clear division of nAMD parameters into the following two groups: one including intraretinal fluid and type 1 and type 2 MNV and the other including SRF, CVH, polypoidal lesions, and HUPI. Conclusions: HUPI revealed that eyes with type 1 MNV and PCV had more pachychoroid-like features than eyes with type 2 MNV. HUPI was tightly associated with CVH and SRF but not MNV per se in nAMD parameters, reinforcing the pathoetiological concept of differentiating pachychoroid from typical nAMD.},
}
@article {pmid40364185,
year = {2025},
author = {Ota, H and Takeuchi, J and Nonogaki, R and Tamura, K and Kominami, T},
title = {Pneumatic Displacement and Anti-VEGF Therapy for Submacular Hemorrhage in Neovascular Age-Related Macular Degeneration: A Retrospective Study.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364185},
issn = {2077-0383},
abstract = {Background/Objectives: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) can lead to significant vision loss, and the optimal management strategy remains uncertain. This study aimed to evaluate the efficacy and safety of pneumatic displacement (PD) without tissue plasminogen activator (t-PA) for SMH secondary to nAMD. Methods: A retrospective analysis was conducted on 22 eyes with SMH secondary to nAMD treated with PD without t-PA. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of intravitreal injections, and postoperative complications were assessed at baseline and follow-up. Multiple logistic regression analyses were used to identify factors associated with visual outcomes. Results: In the 22 eyes that completed the 6-month follow-up, BCVA (logMAR) was 0.88 ± 0.46 at baseline and 0.76 ± 0.63 at 6 months (p = 0.24). In the 15 eyes with 12-month follow-up, BCVA improved significantly from 0.92 ± 0.47 at baseline to 0.56 ± 0.51 at 12 months (p = 0.01). CRT significantly decreased at 3 months (p < 0.01). During this period, patients received an average of 8.13 ± 2.90 intravitreal anti-vascular endothelial growth factor (VEGF) injections. A shorter duration from symptom onset to treatment was associated with better visual outcomes (p = 0.02). Postoperative vitreous hemorrhage occurred in 31.8% of cases. Conclusions: PD without t-PA, in combination with anti-VEGF therapy, improved visual outcomes over 12 months. Early intervention and continuous anti-VEGF administration appear to be key factors in optimizing treatment outcomes. Further studies are needed to establish standardized treatment protocols for SMH associated with nAMD.},
}
@article {pmid40364109,
year = {2025},
author = {Raju, P and Yu, M},
title = {Clinical Applications of the Cone Contrast Test in Ophthalmology and Neurology.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364109},
issn = {2077-0383},
support = {P30-EY025585/NH/NIH HHS/United States ; },
abstract = {Color vision is a critical aspect of human visual perception, yet traditional assessments often lack quantitative precision. The Rabin Cone Contrast Test and its successors offer objective, standardized measurements of cone-specific contrast sensitivity. These tests improve the detection and classification of color vision deficiencies and can facilitate the monitoring of color vision deficits in inherited retinal diseases, cone dystrophies, optic neuropathies, and brain injuries. Integrating quantitative color vision testing into clinical practice presents a more reliable, reproducible, and functionally relevant evaluation, highlighting its value in disease diagnosis, characterization, and management.},
}
@article {pmid40364054,
year = {2025},
author = {Frizziero, L and Midena, G and Danieli, L and Torresin, T and Perfetto, A and Parrozzani, R and Pilotto, E and Midena, E},
title = {Hyperreflective Retinal Foci (HRF): Definition and Role of an Invaluable OCT Sign.},
journal = {Journal of clinical medicine},
volume = {14},
number = {9},
pages = {},
pmid = {40364054},
issn = {2077-0383},
abstract = {Background: Hyperreflective retinal foci (HRF) are small, discrete, hyperreflective elements observed in the retina using optical coherence tomography (OCT). They appear in many retinal diseases and have been linked to disease progression, treatment response, and prognosis. However, their definition and clinical use vary widely, not just between different diseases, but also within a single disorder. Methods: This perspective is based on a review of peer-reviewed studies examining HRF across different retinal diseases. The studies included analyzed HRF morphology, distribution, and clinical relevance using OCT. Particular attention was given to histopathological correlations, disease-specific patterns, and advancements in automated quantification methods. Results: HRF distribution and features vary with disease type and even within the same disease. A variety of descriptions have been proposed with different characteristics in terms of dimensions, reflectivity, location, and association with back shadowing. Automated OCT analysis has enhanced HRF detection, enabling quantitative analysis that may expand their use in clinical practice. However, differences in software and methods can lead to inconsistent results between studies. HRF have been linked to microglial cells and may be defined as neuro-inflammatory cells (Inflammatory, I-HRF), migrating retinal pigment epithelium cells (Pigmentary, P-HRF), blood vessels (Vascular, V-HRF), and deposits of proteinaceous or lipid elements leaking from vessels (Exudative, E-HRF). Conclusions: HRF are emerging as valuable imaging biomarkers in retinal diseases. Four main types have been identified, with different morphological features, pathophysiological origin, and, therefore, different implications in the management of retinal diseases. Advances in imaging and computational analysis are promising for their incorporation into personalized treatment strategies.},
}
@article {pmid40362317,
year = {2025},
author = {Khan, I and Ramzan, F and Tayyab, H and Damji, KF},
title = {Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {9},
pages = {},
pmid = {40362317},
issn = {1422-0067},
mesh = {Humans ; *Retinal Degeneration/therapy ; Genetic Therapy/methods ; Animals ; Stem Cell Transplantation/methods ; Gene Editing ; Regenerative Medicine/methods ; },
abstract = {Retinal degeneration, characterized by the progressive loss of photoreceptors, retinal pigment epithelium cells, and/or ganglion cells, is a leading cause of vision impairment. These diseases are generally classified as inherited (e.g., retinitis pigmentosa, Stargardt disease) or acquired (e.g., age-related macular degeneration, diabetic retinopathy, glaucoma) ocular disorders that can lead to blindness. Available treatment options focus on managing symptoms or slowing disease progression and do not address the underlying causes of these diseases. However, recent advancements in regenerative medicine offer alternative solutions for repairing or protecting degenerated retinal tissue. Stem and progenitor cell therapies have shown great potential to differentiate into various retinal cell types and can be combined with gene editing, extracellular vesicles and exosomes, and bioactive molecules to modulate degenerative cellular pathways. Additionally, gene therapy and neuroprotective molecules play a crucial role in enhancing the efficacy of regenerative approaches. These innovative strategies hold the potential to halt the progression of retinal degenerative disorders, repair or replace damaged cells, and improve visual function, ultimately leading to a better quality of life for those affected.},
}
@article {pmid40361958,
year = {2025},
author = {Nurjanah, T and Patel, M and Mar, J and Holden, D and Barrett, SC and Yannuzzi, NA},
title = {Expanding Application of Optical Coherence Tomography Beyond the Clinic: A Narrative Review.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {9},
pages = {},
pmid = {40361958},
issn = {2075-4418},
abstract = {Since its introduction, optical coherence tomography (OCT) has significantly progressed in addressing its limitations. By integrating artificial intelligence and multimodal imaging, OCT enhances both speed and image quality while reducing its size. OCT continues to advance, offering new possibilities beyond the in-office setting, including intraoperative applications. This review will explore the different types of home OCT and intraoperative OCT, as well as the uses of each device and their future potential in ophthalmology.},
}
@article {pmid40360847,
year = {2025},
author = {Wu, KY and Dave, A and Nirwal, GK and Giunta, M and Nguyen, VDH and Tran, SD},
title = {Exosome Innovations in Ophthalmology and Sjögren's Syndrome.},
journal = {Advances in experimental medicine and biology},
volume = {1488},
number = {},
pages = {103-131},
pmid = {40360847},
issn = {0065-2598},
mesh = {Humans ; *Sjogren's Syndrome/therapy/metabolism/pathology ; *Exosomes/transplantation/metabolism ; Animals ; *Ophthalmology/methods/trends ; Mesenchymal Stem Cells/metabolism ; },
abstract = {Exosomes, a subset of extracellular vesicles, have emerged as potential therapeutic agents in ophthalmology due to their ability to modulate immune responses, facilitate cellular communication, and promote tissue repair. This chapter explores the potential applications of exosome-based therapies in corneal and anterior segment disorders, retinal diseases, glaucoma, and Sjögren's syndrome. In corneal disorders, mesenchymal stem cell (MSC)-derived secretomes have shown promise in accelerating wound healing, reducing fibrosis, and modulating inflammation, with hydrogel encapsulation strategies potentially enhancing their efficacy. In retinal diseases, exosomes may provide neuroprotective effects in age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa by modulating oxidative stress and inflammation. In glaucoma, secretome-based therapies could support retinal ganglion cell survival and optic nerve regeneration, though their impact on intraocular pressure via the trabecular meshwork remains uncertain. Additionally, exosomal biomarkers in aqueous humor are being investigated as potential diagnostic tools. In Sjögren's syndrome, exosomal biomarkers may facilitate earlier detection, while stem cell-derived exosomes hold promise in modulating immune responses and restoring glandular function. Despite encouraging preclinical and early clinical findings, standardization, scalability, and long-term safety must be addressed before clinical translation. Future research will focus on optimizing exosome-based therapies and exploring their feasibility for ophthalmic applications.},
}
@article {pmid40360203,
year = {2025},
author = {Overbey, K and Romano, F and Ding, X and Bennett, CF and Stettler, I and Garg, I and Ploumi, I and Vingopoulos, F and Yuan, M and Razavi, P and Finn, M and Laíns, I and Patel, NA and Kim, L and Wu, D and Eliott, D and Husain, D and Vavvas, D and Miller, JW and Miller, JB},
title = {Choriocapillaris impairment in dry AMD: insights from swept-source OCT angiography and associations with structural biomarkers.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {9},
pages = {1020-1027},
doi = {10.1136/bjo-2024-326416},
pmid = {40360203},
issn = {1468-2079},
mesh = {Humans ; Cross-Sectional Studies ; *Tomography, Optical Coherence/methods ; Male ; Female ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods ; Aged ; *Geographic Atrophy/physiopathology/diagnosis/diagnostic imaging ; Middle Aged ; Biomarkers ; Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Fundus Oculi ; Capillaries/pathology ; Visual Acuity ; },
abstract = {AIMS: To assess choriocapillaris flow deficit percentage (CCFD%) across stages of dry age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: This cross-sectional, observational study included 270 eyes (182 patients), classified as early (70 eyes), intermediate (121 eyes) and geographic atrophy (GA, 79 eyes).Participants underwent a complete examination including macular 6&#xd7;6&#x2009;mm SS-OCTA scans (PLEX Elite 9000). Scans were reviewed and analysed for subretinal drusenoid deposits (SDDs), retinal pigment epithelium (RPE) atrophy size, incomplete RPE and outer retinal atrophy (iRORA) and drusen volume (3&#x2009;mm). CCFD% was calculated after compensation and binarisation using Phansalkar's method (r=4-15 pixels) in various early treatment for diabetic retinopathy study sectors. Linear mixed-effects models adjusted for age evaluated associations with AMD stages and other imaging biomarkers.<br><br>RESULTS: CCFD% progressively increased with advancing dry AMD stages. Intermediate AMD eyes showed higher CCFD% than early AMD ones across all regions (p<0.001). GA eyes exhibited significantly higher CCFD% compared with early (p<0.001) and intermediate AMD eyes (p<0.001).SDDs were significantly associated with higher CCFD% in early (p<0.01) and intermediate AMD (p<0.05) for almost all regions examined, but not in GA (p>0.05). iRORA presence in iAMD and larger RPE atrophy in GA correlated with increased CCFD% (p<0.001).<br><br>CONCLUSIONS: This study provides a comprehensive reference database for CCFD% across the stages of dry AMD using SS-OCTA. CCFD% increased with AMD severity, iRORA, SDDs, particularly in early and intermediate stages, and RPE atrophy size. Our findings support CCFD% as a valuable biomarker for clinical and research applications, warranting longitudinal studies to validate its prognostic value.},
}
@article {pmid40359463,
year = {2025},
author = {Cozzi, M and Trinco, A and Romano, F and Zweifel, SA and Staurenghi, G and Invernizzi, A},
title = {Assessing Reliability and Agreement in Topographic Measurement of Reticular Pseudodrusen Area: A Multimodal Imaging Approach.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {9},
pages = {1701-1711},
pmid = {40359463},
issn = {1539-2864},
abstract = {PURPOSE: This study aims to assess the reliability and agreement of fundus autofluorescence (FAF), near-infrared reflectance (NIR), and a combination of NIR and dense structural optical coherence tomography (OCT) scans (OCT+NIR) in delineating the areas of reticular pseudodrusen (RPD) in eyes affected by age-related macular degeneration (AMD).<br><br>METHODS: This was a single-center, cross-sectional study. Patients with non-advanced AMD exhibiting signs of RPD on multimodal imaging were enrolled. Two independent masked graders manually delineated the margins of the area occupied by RPD using the three distinct imaging techniques.<br><br>RESULTS: The study included 60 eyes from 51 patients, with a mean age of 81.5 (&#xb1;7.1) years.The intraclass correlation coefficient between the two graders across all imaging modalities was 0.96 for FAF, 0.92 for NIR, and 0.98 for OCT+NIR. The narrowest limits of agreement were observed with OCT+NIR (-4.38 +5.17 mm 2). Foveal involvement and age were significantly correlated with larger RPD area (p =0.036 and p=0.019 respectively). Pairwise comparisons of square root-transformed RPD areas indicated that FAF detected a significantly larger RPD area compared to other methods (p <0.001).<br><br>CONCLUSIONS: These findings validate OCT+NIR as a reliable approach for measuring RPD areas, potentially serving as a critical biomarker for AMD in future clinical trials.},
}
@article {pmid40359333,
year = {2025},
author = {Khateb, S and Ghiam, S and Safran, J and Martel, JN and Alabek, M and Nischal, KK and Errera, MH and Eller, AW and Friberg, TR and Chowers, I and Sahel, JA and Banin, E and Rosin, B},
title = {Bilateral Idiopathic Multifocal Pigment Epithelial Detachments: A Case Series and Review of Literature.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004513},
pmid = {40359333},
issn = {1539-2864},
abstract = {PURPOSE: Description of longitudinal follow-up of 13 patients diagnosed with Idiopathic Multifocal Pigment Epithelial Detachments (IMPED), a rare condition first described by Gass et al., in 2005.<br><br>METHODS: This retrospective case series included 13 patients in the first to sixth decades of life who presented with multiple bilateral PEDs, confirmed by Optical Coherence Tomography. Ancillary imaging included fundus autofluorescence and angiography to exclude alternative diagnoses such as Central Serous Chorioretinopathy and Polypoidal Choroidovasculopathy. Electrophysiology testing, including full-field electroretinography (FFERG) and electrooculography (EOG), assessed both retinal and pigment epithelium function. Visual acuity (VA) was documented over a mean follow-up of 6.5 years (range: 0.1-26.4 years).<br><br>RESULTS: All patients demonstrated stable VA during follow-up. Electrophysiology was normal in tested patients (FFERG: 9/13, EOG: 7/13). Genetic testing (10/13) was non-diagnostic. Two patients (including a patient previously receiving anti-VEGF without exudation) exhibited outer retinal atrophy. One patient developed a choroidal neovascularization (CNV) during follow-up, which resolved with intravitreal aflibercept.<br><br>CONCLUSION: IMPED should remain a diagnosis of exclusion, confirmed after sufficient follow-up demonstrating no progression. While our study implies a generally favorable prognosis, continuous monitoring is necessary to assess long-term risks, including potential complications such as the development of CNV and/or atrophy.},
}
@article {pmid40358170,
year = {2025},
author = {Song, YS and Park, S and Fisk, D and Sorenson, CM and Sheibani, N},
title = {Isolation and Characterization of Mouse Choroidal Melanocytes and Their Proinflammatory Characteristics.},
journal = {Cells},
volume = {14},
number = {9},
pages = {},
pmid = {40358170},
issn = {2073-4409},
support = {P30 EY016665/EY/NEI NIH HHS/United States ; EY034646/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; R01 EY030076/EY/NEI NIH HHS/United States ; AMD Research Award//Arthur and Nancy Nesbit AMD fund/ ; AMD Research Award//Carl Marshall Reeves &amp; Mildred Almen Reeves Foundation/ ; EY030076/EY/NEI NIH HHS/United States ; Endoument//RRF/Daniel Albert Chair/ ; Endoument//Retina Research Foundation/ ; R21 EY034646/EY/NEI NIH HHS/United States ; Unrestricted Award to the Deaprtment of Ophthalmology and visual Sciences//Research to Prevent Blindness/ ; AMD Research Award//Pat and Jay Smith AMD Innovation Fund/ ; },
mesh = {Animals ; *Melanocytes/pathology/metabolism/cytology ; *Choroid/pathology/cytology ; Mice ; *Inflammation/pathology ; Mice, Inbred C57BL ; *Cell Separation/methods ; Cells, Cultured ; },
abstract = {Melanocytes are a major cellular component of the choroid which aids in the maintenance of choroidal integrity and vision. Unfortunately, our knowledge regarding the cell autonomous melanocyte function, in preserving choroidal health and the ocular pathologies associated with choroidal dysfunction, remain largely unknown. The ability to culture melanocytes has advanced our knowledge regarding the origin and function of these cells in choroidal homeostasis and vision. However, the culture of murine choroid melanocytes has not been previously reported. Here, we describe a method for the isolation of melanocytes from the mouse choroid, as well as the delineation of many of their cellular characteristics, including the expression of various cell-specific markers, cell adhesion molecules, melanogenic capacity, and inflammatory responses to various extracellular stressors. Unraveling the molecular mechanisms that regulate melanocyte functions will advance our understanding of their role in choroidal homeostasis and how alterations in these functions impact ocular diseases that compromise vision.},
}
@article {pmid40358157,
year = {2025},
author = {Kowalczuk, L and Dornier, R and Navarro, A and Jeunet, F and Moser, C and Behar-Cohen, F and Mantel, I},
title = {Adaptive Optics-Transscleral Flood Illumination Imaging of Retinal Pigment Epithelium in Dry Age-Related Macular Degeneration.},
journal = {Cells},
volume = {14},
number = {9},
pages = {},
pmid = {40358157},
issn = {2073-4409},
support = {Project ASSESS retinAI phase contrast imaging for Early diagnoSiS_Activity 20694//European Institute of Innovation and Technology/ ; Project 56126.1 IMPULSE- IRIS Imaging Retinal cells In degenerative diSeases//Innosuisse - Swiss Innovation Agency/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; Aged ; Male ; Female ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging/pathology ; Middle Aged ; Prospective Studies ; *Geographic Atrophy/diagnostic imaging/pathology ; Aged, 80 and over ; },
abstract = {Adaptive optics-transscleral flood illumination (AO-TFI) is a novel imaging technique with potential for detecting retinal pigment epithelium (RPE) changes in dry age-related macular degeneration (AMD). This single-center prospective study evaluated its ability to visualize pathological features in AMD. AO-TFI images were acquired using the prototype Cellularis[®] camera over six 5 × 5° macular zones in patients with good fixation and no exudative changes. Conventional imaging modalities, including spectral-domain optical coherence tomography (OCT), color fundus photography and fundus autofluorescence, were used for comparison. AO-TFI images were correlated with OCT using a custom method (Fiji software, v. 2.9). Eleven eyes of nine patients (70 ± 8.3 years) with early (n = 5), intermediate (n = 1) and atrophic (n = 5) AMD were analyzed. AO-TFI identified relevant patterns in dry AMD. RPE cell visibility was impaired in affected eyes, but AO-TFI distinguished cuticular drusen with hyporeflective centers and bright edges, large ill-defined drusen and stage 3 subretinal drusenoid deposits as prominent hyperreflective spots. It provided superior resolution for small drusen compared to OCT and revealed crystalline structures and hyporeflective dots in atrophic regions. Atrophic borders remained isoreflective unless RPE displacement was absent, allowing precise delineation. These findings highlight AO-TFI's potential as a sensitive imaging tool for characterizing early AMD and clinical research.},
}
@article {pmid40356067,
year = {2025},
author = {Zipfel, PF and Heidenreich, K},
title = {The 4 functional segments of Factor H: Role in physiological target recognition and contribution to disease.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
volume = {214},
number = {9},
pages = {2150-2164},
doi = {10.1093/jimmun/vkaf065},
pmid = {40356067},
issn = {1550-6606},
support = {SFB 1192//DFG/ ; },
mesh = {Humans ; *Complement Factor H/genetics/immunology/chemistry/metabolism ; Complement Activation/immunology ; Animals ; Complement C3b/metabolism/immunology ; Atypical Hemolytic Uremic Syndrome/immunology ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology/genetics ; },
abstract = {Factor H controls proximal complement activation, and its dysfunction leads to diseases that often manifest in the kidney. Structural and functional analyses have identified 4 distinct functional segments: an N-terminal regulatory unit, a cell binding unit, a segment with combined low-affinity C3b and heparin sites, and a C-terminal recognition or sensor unit with overlapping C3b/C3d and heparin sites. Three segments are linked to diseases. The regulatory segment is affected in C3 glomerulopathy and antineutrophil cytoplasmic antibody-associated vasculitis. The second segment includes the Y402H polymorphism of age-related macular degeneration, is associated with different types of cancer, and is targeted by pathogens. The C-terminal sensor segment is involved in atypical hemolytic uremic syndrome, in FHR1:FHR3 deficient and autoantibody-positive hemolytic uremic syndrome form and is exploited by pathogens. Factor H function is modulated by Factor H like protein 1 and FHR1, 2 plasma proteins that share segments with Factor H. This interplay is critical for fine-tuning local complement. Understanding Factor H's physiological role, as well as the impact of its absence, mutations, or autoantibody targeting, provides insights into disease mechanisms and provides opportunities for therapeutic intervention by using full-length Factor H, its fragments, or complement-modulatory compounds.},
}
@article {pmid40355704,
year = {2025},
author = {Chandak, S and Gurudas, S and Pakeer Muhammed, R and Keskin, A and Thottarath, S and Ghanchi, F and Grabowska, A and Talks, SJ and Pearce, I and McKibbin, M and Kotagiri, A and Menon, G and Burton, BJL and Gale, R and Sivaprasad, S},
title = {Visual outcome following initiation of first injection versus after three monthly doses of aflibercept 2 mg for treatment naïve age-related macular degeneration to inform clinical trial designs: PRECISE Report No. 6.},
journal = {Eye (London, England)},
volume = {39},
number = {11},
pages = {2194-2203},
pmid = {40355704},
issn = {1476-5454},
support = {SIVS1045//Boehringer Ingelheim/ ; },
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity/physiology/drug effects ; Aged ; Intravitreal Injections ; Male ; Female ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Drug Administration Schedule ; },
abstract = {PURPOSE: To study the outcome of the first dose versus three monthly doses of 2 mg aflibercept in the initiation phase of neovascular age-related macular degeneration (nAMD) to inform future clinical trial design on novel durable agents. These agents may take time to act and so initial dosing with aflibercept 2 mg is required for immediate effect.<br><br>METHODS: Visual acuity (VA) outcomes and associations with baseline VA and OCT characteristics were analysed using logistic regression via generalised estimating equations. In addition, VA outcomes based on different combinations of eligibility criteria were assessed.<br><br>RESULTS: A total of 1999 eyes of 1862 patients were analysed. The mean age was 79.3 (SD 7.8) years. The mean presenting VA was 58.0 (SD 14.5) ETDRS letter score. A statistical difference in VA was found after first injection (visit 2, 61.6, SD 14.3 ETDRS letter score) and after three monthly injections (visit 4, 62.7, SD 14.9 ETDRS letter score) (P&#x2009;<&#x2009;0.001). Lower baseline VA and OCT features suggestive of structural changes in the fovea are associated with lower VA after both first and post- initiating doses. Eyes with baseline VA&#x2009;>&#x2009;/&#x2009;=&#x2009;54 letters alone had similar VA outcomes to eyes with both VA&#x2009;>&#x2009;/&#x2009;=&#x2009;54 letters and central subfield thickness (CST) of <500 microns.<br><br>CONCLUSION: Mean VA outcomes after three monthly anti-VEGF injections are significantly better than after the first initiating dose. However, baseline OCT characteristics associated with VA in these two timepoints are not clinically different.},
}
@article {pmid40355192,
year = {2025},
author = {Han, X and Hua, Z and Chen, H and Yang, J},
title = {Cathepsins and age-related macular degeneration: A Mendelian randomization study unveiling causal relationships.},
journal = {Medicine},
volume = {104},
number = {19},
pages = {e42357},
pmid = {40355192},
issn = {1536-5964},
mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/genetics ; *Cathepsins/genetics/blood ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Cathepsin B/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment and blindness in older adults, profoundly affecting millions of individuals worldwide. Cathepsins are a crucial class of proteolytic enzymes that participates in multiple biological process. However, the role of cathepsins in AMD still remains unclear. This study aims to probe into the causal relationship between cathepsins and AMD using a 2-sample Mendelian randomization (MR). Instrumental variables associated with exposure (cathepsins) and the outcome (AMD) were sourced from published genome-wide association studies. To estimate the causal effects, methodologies such as inverse variance weighted, MR-Egger, and weighted median estimation (WM) were employed. Reverse MR and multivariate MR analyses were also performed. The elevated levels of cathepsin B significantly increased the risk of dry AMD, with an odds ratio (OR) of 1.068 (95% CI = 1.007-1.133) and a P-value of .029). Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or pleiotropy. Reverse MR analyses indicated that total AMD might elevate levels of cathepsin E (OR = 1.04, P = .029). Multivariate MR analysis showed significant associations between specific cathepsins and AMD subtypes, including cathepsin G and cathepsin O with significantly increasing risk. The study revealed a potential causal effect of cathepsin B on AMD, especially dry AMD. These findings provide potential therapeutic targets for AMD, and further research is needed to understand the underlying mechanisms.},
}
@article {pmid40354880,
year = {2025},
author = {Liaño Sanz-Diez de Ulzurrun, G and Escámez-Fernández, P and Hernáez-Leonato, JM and Son-Camey, B and Rosado-Cerro, I and Arruabarrena, C},
title = {Pigment epithelial detachments in age related macular degeneration.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {100},
number = {6},
pages = {340-350},
doi = {10.1016/j.oftale.2025.05.005},
pmid = {40354880},
issn = {2173-5794},
mesh = {Humans ; *Retinal Detachment/etiology/diagnostic imaging/diagnosis ; *Macular Degeneration/complications ; *Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence ; },
abstract = {Pigment epithelial detachments (PEDs) form a heterogeneous group of lesions of diverse prognosis and treatment that have in common the pathologic elevation of the retinal pigment epithelium plane and its detachment from the underlying layers. Although PEDs are a common finding in age-related macular degeneration, especially in its exudative forms, the diagnostic characterization and prognostic estimation of these lesions is a clinical challenge that necessarily requires a multimodal imaging approach. This review presents the clinical characteristics of the different groups of PED, their diagnostic imaging profile, as well as their natural history.},
}
@article {pmid40354066,
year = {2025},
author = {Yang, J and Wu, H and Li, Q and Guo, J and Yao, J and Pan, S and Wu, X and Huang, H and Chen, R and Chen, J and Wang, Y and Peng, Y and Wu, F and Hu, J},
title = {A Simple and Rapid Method for Simultaneous Isolation of Mouse Retina and RPE Wholemounts.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {5},
pages = {14},
pmid = {40354066},
issn = {2164-2591},
mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/cytology ; Mice, Inbred C57BL ; *Retina/cytology ; Tissue Fixation/methods ; },
abstract = {PURPOSE: Retina and retinal pigment epithelium (RPE) wholemounts are important models for studying the pathophysiology of retinal-related ophthalmic diseases, such as age-related macular degeneration and diabetic retinopathy. Currently, there is no method available for simultaneously obtaining retina and RPE wholemounts. The aim of this study is to develop a simple, rapid, and effective technique for the simultaneous isolation of mouse retina and RPE wholemounts.<br><br>METHODS: We developed a novel, streamlined procedure for the efficient isolation of intact retina and RPE wholemounts from mouse eyes. The method involves minimal dissection and uses basic laboratory equipment, allowing the entire process to be completed in approximately 2 to 5&#xa0;minutes per sample. The study also explores the impact of different fixation times on the structural integrity and quality of both retina and RPE wholemounts (3&#xa0;hours in 4% paraformaldehyde [PFA], 30 minutes < 1 &#xd7; phosphate-buffered saline [PBS] < 3 hours).<br><br>RESULTS: The new method consistently yields high-quality, intact retina and RPE wholemounts, with excellent structural integrity suitable for downstream imaging and molecular analyses. The technique significantly reduces preparation time. Optimal fixation conditions were identified, with 3&#xa0;hours of fixation in 4% PFA and PBS incubation times between 30&#xa0;minutes and 3&#xa0;hours yielding the best results. The approach showed higher tissue integrity (80% vs. 45%) and improved staining quality of photoreceptor and ganglion cells. Additionally, the method is highly reproducible and effective for wholemount preparations from both young and older mice (6 and 12&#xa0;months).<br><br>CONCLUSIONS: This study presents a significant advancement in the preparation of retina and RPE wholemounts. The simplicity, speed, and preservation of tissue integrity of the new method make it a valuable tool for ophthalmic disease research. Its potential applications include drug screening, gene therapy, and disease modeling, offering significant advantages in time efficiency, reproducibility, and the quality of morphological analysis.},
}
@article {pmid40353550,
year = {2025},
author = {Yusef, Y and Plyukhova, AA and Yusef, N},
title = {[Artificial intelligence in assessment of individual risks of age-related macular degeneration progression].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {2},
pages = {123-128},
doi = {10.17116/oftalma2025141021123},
pmid = {40353550},
issn = {0042-465X},
mesh = {Humans ; *Macular Degeneration/diagnosis/physiopathology ; *Artificial Intelligence ; *Tomography, Optical Coherence/methods ; Disease Progression ; Risk Assessment/methods ; Early Diagnosis ; },
abstract = {Age-related macular degeneration (AMD) is a progressive degenerative retinal disease and a leading cause of blindness in older adults worldwide. According to numerous studies, the number of affected individuals reached 196 million in 2020, with projections estimating an increase to 288 million by 2040, including 18.6 million cases of advanced AMD. The advent of optical coherence tomography (OCT) has enabled researchers and clinicians to characterize microstructural changes in different retinal layers at earlier disease stages and improve monitoring strategies. Important steps have been taken to develop algorithms capable of recognizing early signs of AMD, assessing its severity, and predicting progression. These algorithms have formed the basis for artificial intelligence (AI)-driven systems applicable to any hardware or software exhibiting intelligent behavior. OCT imaging allows for the identification of biomarkers whose presence or interaction with other factors predict transition from intermediate to advanced AMD. The obtained data can provide deeper insights into the pathogenesis of intermediate AMD, enhance early diagnosis for timely intervention, and facilitate the search for new treatment options. Artificial intelligence could make this process easier, simpler, less time-consuming, and more accurate by integrating structural OCT data with genetic risk indicators and lifestyle characteristics. However, the results are still inconsistent due to factors leading to limited result reliability, such as database quality, sample sizes, and data acquisition methods.},
}
@article {pmid40353548,
year = {2025},
author = {Voskresenskaya, AA and Sarkizova, MB and Khodzhaev, NS and Kudlay, DA and Kakunina, SA and Borozinets, AY and Pozdeyeva, NA},
title = {[Biosimilars of ranibizumab in retinal diseases: new possibilities in ophthalmology].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {2},
pages = {106-116},
doi = {10.17116/oftalma2025141021106},
pmid = {40353548},
issn = {0042-465X},
mesh = {Humans ; *Ranibizumab/pharmacology/therapeutic use/pharmacokinetics ; *Biosimilar Pharmaceuticals/pharmacology/therapeutic use ; Angiogenesis Inhibitors/pharmacology ; Russia ; *Retinal Diseases/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ophthalmology/methods ; },
abstract = {The development of biological therapeutic agents has provided new opportunities for treating neovascular age-related macular degeneration (nAMD) using humanized monoclonal antibodies (mAbs) targeting vascular endothelial growth factor A (VEGF-A). The emergence of biosimilars of anti-VEGF agents can significantly improve treatment accessibility and its effectiveness by increasing patient adherence. The development of biosimilars involves comparative studies with the original drug to establish equivalence in physicochemical and biological properties, efficacy, and safety. Biosimilar development programs include extensive analytical and preclinical studies to compare structural and functional components with the original bioproduct, and clinical trials are conducted to prove bioequivalence and therapeutic equivalence. The process of development and registration of the biosimilars is strictly regulated and has no significant differences in Russia, the EU and the US. Currently, more than 10 biosimilars of ranibizumab have been approved worldwide, in Russia it is the drug Laxolan (AO GENERIUM). The introduction of a domestic biosimilar of ranibizumab into clinical practice allows reduction of the costs of retinal disease treatment while maintaining the efficacy and safety of antiangiogenic therapy.},
}
@article {pmid40353546,
year = {2025},
author = {Udom, GJ and Oritsemuelebi, B and Frazzoli, C and Bocca, B and Ruggieri, F and Orisakwe, OE},
title = {[Heavy metals and derangement in carbohydrate metabolism in eye diseases: a systematic review].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {2},
pages = {89-100},
doi = {10.17116/oftalma202514102189},
pmid = {40353546},
issn = {0042-465X},
mesh = {Humans ; *Carbohydrate Metabolism/drug effects ; *Eye Diseases/metabolism/physiopathology ; *Metals, Heavy/adverse effects/toxicity ; Oxidative Stress/drug effects ; },
abstract = {PURPOSE: To uncover the negative impacts of heavy metals on carbohydrate metabolism, their mechanisms and contributory factors, as well as their role on the etiopathogenesis, pathophysiology, and progression of eye diseases.<br><br>MATERIAL AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), various databases were searched (e.g., Scopus, PubMed, etc.) to collect evidence on the link and role of heavy metals in carbohydrate metabolism and pathogenesis of eye diseases. Included studies were appraised for quality using the Critical Appraisal Skills Programme checklists and extracted data were analyzed using the narrative synthesis method.<br><br>RESULTS: Of the 128 papers retrieved, 24 papers met the inclusion criteria. Heavy metals are associated with the onset and progression of diabetes and eye diseases secondary to diabetes (age-related macular degeneration, cataract, and diabetic retinopathy) majorly via toxic interference (induction, inhibition and/or deactivation) of glucose metabolizing enzymes and oxidative stress. The etiology of DR is intricate and includes the simultaneous disruption of several metabolic and signaling mechanisms within the retinal neurovascular unit. The retina is more susceptible to metal-induced toxicities due to the high affinity of heavy metals to melanin content of the retinal epithelium.<br><br>CONCLUSION: This study emphasizes the harmful effects of chronic and intermittent exposure to heavy metals, suggesting no safe exposure levels. To prevent eye diseases secondary to heavy metals-induced altered carbohydrate metabolism, metal chelators, low glycemic diets, and lifestyle modifications should be exploited among vulnerable populations.},
}
@article {pmid40350849,
year = {2025},
author = {Li, B and Guo, S and Zhu, Y and Wang, XS and Wei, DD and Kang, HJ and Zhang, WH and Duan, JA},
title = {[Ameliorative effects of Lycii Fructus-Chrysanthemi Flos at different ratios on retinal damage in mice].},
journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica},
volume = {50},
number = {3},
pages = {732-740},
doi = {10.19540/j.cnki.cjcmm.20240912.701},
pmid = {40350849},
issn = {1001-5302},
mesh = {Animals ; Mice ; *Retina/drug effects/metabolism/injuries ; Male ; *Lycium/chemistry ; *Drugs, Chinese Herbal/administration &amp; dosage ; *Chrysanthemum/chemistry ; NF-kappa B/metabolism/genetics ; Humans ; *Retinal Diseases/drug therapy/genetics/metabolism ; NF-E2-Related Factor 2/genetics/metabolism ; Oxidative Stress/drug effects ; Flowers/chemistry ; Heme Oxygenase-1/metabolism/genetics ; },
abstract = {This study aimed to compare the ameliorative effects of Lycii Fructus and Chrysanthemi Flos at different ratios on retinal damage in mice and to elucidate the underlying mechanisms. A retinal injury model was established by intraperitoneal injection of sodium iodate(NaIO_3) solution. The mice were divided into the following groups: blank group, model group, positive drug(AREDS 2) group, low-and high-dose groups of Lycii Fructus and Chrysanthemi Flos at 1∶1, low-and high-dose groups at 3∶1, and low-and high-dose groups at 1∶3. Administration was carried out 15 days after modeling. The visual acuity of the mice was assessed using the black-and-white box test. The fundus was observed using an optical coherence tomography device, and retinal thickness was measured. HE staining was used to observe the morphology and pathological changes of the retina. The levels of oxidative factors in serum and ocular tissues were measured using assay kits. The levels of inflammatory factors in serum and ocular tissues were detected by enzyme-linked immunosorbent assay(ELISA), and the expression of Nrf2, HO-1, and NF-κB proteins in ocular tissues was analyzed by Western blot. The results showed that after administration of Lycii Fructus and Chrysanthemi Flos at different ratios, the model group showed improved retinal thinning and disordered arrangement of retinal layers, elevated content of SOD and GSH in the serum and ocular tissues, and reduced levels of MDA, TNF-α, IL-1β, and IL-6. Lycii Fructus and Chrysanthemi Flos at 1∶1 and 1∶3 showed better improvement effects. The combination significantly upregulated the expression levels of Nrf2 and HO-1 and downregulated the expression of NF-κB p65. These results indicate that Lycii Fructus and Chrysanthemi Flos at different ratios can improve retinal damage, reduce oxidative stress, and alleviate inflammation in both the body and ocular tissues of mice. The mechanism may be related to the regulation of the Nrf2/HO-1 and NF-κB signaling pathways in ocular tissues. These findings provide a theoretical basis for the clinical application of Lycii Fructus and Chrysanthemi Flos in the treatment of dry age-related macular degeneration.},
}
@article {pmid40349982,
year = {2025},
author = {London, NJS and Cheung, CMG and Michels, S and Kotecha, A and Margaron, P and Souverain, A and Willis, JR and Lai, TYY},
title = {Outcomes by Faricimab Treatment Interval at Week 48 of TENAYA-LUCERNE Phase III Trials in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {11},
pages = {1081-1089},
doi = {10.1016/j.oret.2025.05.004},
pmid = {40349982},
issn = {2468-6530},
mesh = {Humans ; *Visual Acuity ; Double-Blind Method ; Male ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis ; Middle Aged ; Treatment Outcome ; Aged ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Time Factors ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Fundus Oculi ; Angiopoietin-2/antagonists &amp; inhibitors ; *Macula Lutea/pathology ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To assess the visual and anatomic outcomes by individualized treatment intervals at week 48 in patients with neovascular age-related macular degeneration (nAMD) treated with the dual angiopoietin-2/VEGF-A inhibitor faricimab in a post hoc analysis of pooled data from TENAYA/LUCERNE.<br><br>DESIGN: TENAYA/LUCERNE (NCT03823287/NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled, noninferiority phase III trials.<br><br>PARTICIPANTS: Treatment-na&#xef;ve patients &#x2265;50 years of age with nAMD randomized to the faricimab up to every 16 weeks (Q16W; n = 665) arm.<br><br>METHODS: Patients in the faricimab arm received 4 initial doses every 4 weeks through week 12. At weeks 20 and 24, they were assigned to fixed every 8 weeks (Q8W), every 12 weeks (Q12W), or every 16 weeks (Q16W) treatment intervals through week 60, based on prespecified central subfield thickness (CST) or best-corrected visual acuity (BCVA) disease activity criteria or presence of new macular hemorrhage, per investigator clinical examination. The primary analysis was at week 48.<br><br>MAIN OUTCOME MEASURES: Mean changes from baseline in BCVA and CST through week 48 by treatment interval group.<br><br>RESULTS: At week 48, the proportion of faricimab-treated patients on each treatment interval was 45.3% (Q16W), 33.4% (Q12W), and 21.2% (Q8W). The baseline patient characteristics were well balanced across faricimab treatment intervals. However, patients assigned to treatment at Q16W and Q12W had less severe disease at baseline than patients assigned to Q8W. All patients showed sustained BCVA gains and CST reductions through week 48. Mean (95% confidence interval) change from baseline in BCVA was +7.9 letters (6.6 to 9.2), +4.0 letters (2.2 to 5.7), and +5.3 letters (2.4 to 8.2); and that in CST was -142.9 &#x3bc;m (-156.9 to -128.9), -112.5 &#x3bc;m (-131.0 to -94.1), and -165.1 &#x3bc;m (-193.8 to -136.4) for Q16W, Q12W, and Q8W, respectively.<br><br>CONCLUSIONS: Vision and anatomic improvements were achieved and maintained in all faricimab individualized treatment interval groups, with patients treated at longer intervals having more stable outcomes with fewer injections. The clinically relevant disease activity criteria based on vision or anatomy allowed treatment of patients with nAMD to be rapidly extended after the initial dosing phase while maintaining visual gains through week 48 of TENAYA/LUCERNE.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40348918,
year = {2025},
author = {Sherif, M and Derradji, Y and Safi, A and Mantel, I},
title = {Long-term outcomes of the observe-and-plan regimen in treating neovascular age-related macular degeneration: a retrospective real-life analysis.},
journal = {Eye (London, England)},
volume = {39},
number = {11},
pages = {2188-2193},
pmid = {40348918},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; Aged ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Male ; Female ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Treatment Outcome ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND/OBJECTIVES: This study aimed to evaluate the long-term (7 years) outcome of visual acuity in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents following the observe-and-plan regimen.<br><br>SUBJECTS/METHODS: A total of 195 eyes from 181 patients with nAMD (mean age 79.5&#x2009;&#xb1;&#x2009;6.9 years), with a mean follow-up duration of 66&#x2009;&#xb1;&#x2009;37 months, treated with intravitreal anti-VEGF (ranibizumab or aflibercept) were included in this retrospective study. The principles of the observe-and-plan regimen were followed, with follow-up exceeding 3 years in real-life settings. Data collected included visual acuity (VA), number of injections and visits, central retinal thickness, and any complications over 7 years from baseline.<br><br>RESULTS: The mean baseline VA was 63&#x2009;&#xb1;&#x2009;17 Early Treatment of Diabetic Retinopathy Study letters (Snellen equivalent 20/63), improving to 73&#x2009;&#xb1;&#x2009;14 at year 1. The initial visual gain was slightly reduced with a final mean VA of 70&#x2009;&#xb1;&#x2009;18 letters (Snellen equivalent 20/40) at year 7. The mean central macular thickness decreased significantly from 375&#x2009;&#xb1;&#x2009;129 at baseline to 276&#x2009;&#xb1;&#x2009;75 at year 1 and to 279&#x2009;&#xb1;&#x2009;87 at year 7. The mean annual number of injections decreased from 8.7&#x2009;&#xb1;&#x2009;3.2 in year 1 to 6.7&#x2009;&#xb1;&#x2009;3.7 in year 2 and to 5.5&#x2009;&#xb1;&#x2009;2.8 in year 7. The mean annual number of visits remained constant throughout, with 4.1&#x2009;&#xb1;&#x2009;1.3 visits in year 1 and 4.7&#x2009;&#xb1;&#x2009;1.7 in year 7.<br><br>CONCLUSIONS: The observe-and-plan regimen was very efficient for treating nAMD in real-life settings, reducing the clinical burden on the medical system and patients, with excellent functional and structural long-term results.},
}
@article {pmid40348395,
year = {2025},
author = {Liu, Z and Huang, Y and Jin, L and Pan, C and Han, X and Zheng, Y},
title = {Validation of a self-administered Home ETDRS visual acuity testing (H-ETDRS) for self-monitoring vision changes in retinal diseases.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {9},
pages = {1012-1019},
doi = {10.1136/bjo-2024-326283},
pmid = {40348395},
issn = {1468-2079},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Reproducibility of Results ; Aged ; Middle Aged ; *Vision Tests/methods/instrumentation ; *Diabetic Retinopathy/physiopathology/diagnosis ; *Macular Degeneration/physiopathology/diagnosis ; Aged, 80 and over ; Adult ; },
abstract = {OBJECTIVE: To validate a self-administered Home Early Treatment Diabetic Retinopathy Study (H-ETDRS) visual acuity (VA) test and to assess its accuracy in detecting VA decline in patients with retinal diseases.<br><br>METHODS: A validation group of 156 participants and a testing group of 100 participants with diabetic retinopathy and age-related macular degeneration were recruited. All participants underwent monocular distance best-corrected VA (BCVA) tests in the study eye using the standard ETDRS (S-ETDRS) charts in clinic and the H-ETDRS device in a simulated home setting. Participants in the validation group repeated both methods. H-ETDRS letter scores were compared with S-ETDRS scores, evaluating mean difference and test-retest reliability (TRR). Intraclass correlation coefficients (ICCs) were calculated to measure the agreement. Participants in the testing group repeated both methods with a Bangerter filter density of 0.6 to simulate BCVA change. The performance of H-ETDRS in detecting acuity change was evaluated, with S-ETDRS serving as the standard.<br><br>RESULTS: For the validation group, the mean difference between S-ETDRS and H-ETDRS scores was -1.38 letters (95% limits of agreement (LOA) -6.99 to 4.22). The scores of the two tests were highly correlated with an ICC of 0.98. The mean differences between initial test and retest scores were 0.11 letters (95% LOA -2.62 to 2.84) for S-ETDRS and -0.13 letters (95% LOA -5.64 to 5.38) for H-ETDRS. The ICCs of test-retest letter scores were 1.00 for S-ETDRS and 0.98 for H-ETDRS. For participants in the testing group who showed BCVA decline of one line or more with Bangerter filter, 96.7% were able to detect VA changes using H-ETDRS.<br><br>CONCLUSIONS AND RELEVANCE: The H-ETDRS test demonstrates high TRR and good concordance with S-ETDRS test for retinal patients. The H-ETDRS is viable for self-monitoring VA changes in retinal diseases, however, further validation studies in actual home settings are warranted.},
}
@article {pmid40348352,
year = {2025},
author = {Keenan, TDL},
title = {Comment on "Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration".},
journal = {American journal of ophthalmology},
volume = {276},
number = {},
pages = {411-412},
doi = {10.1016/j.ajo.2025.04.044},
pmid = {40348352},
issn = {1879-1891},
}
@article {pmid40347925,
year = {2025},
author = {Yang, CC and Jiang, Q and Xue, JS},
title = {Comprehensive multi-omics and pharmacokinetics reveal sclareol's role in inhibiting ocular neovascularization.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {143},
number = {},
pages = {156817},
doi = {10.1016/j.phymed.2025.156817},
pmid = {40347925},
issn = {1618-095X},
mesh = {Animals ; *Diterpenes/pharmacokinetics/pharmacology ; Mice ; *Choroidal Neovascularization/drug therapy ; Mice, Inbred C57BL ; Humans ; Endothelial Cells/drug effects ; Molecular Docking Simulation ; Male ; *Angiogenesis Inhibitors/pharmacology/pharmacokinetics ; Administration, Oral ; *Retinal Neovascularization/drug therapy ; Cell Proliferation/drug effects ; Multiomics ; },
abstract = {BACKGROUND: Ocular neovascularization, a hallmark of several vision-threatening diseases, including retinopathy of prematurity (ROP) and wet age-related macular degeneration (wet AMD), is commonly treated with intravitreal injections of anti-VEGF agents. However, these treatments are limited by invasiveness and drug resistance, highlighting the need for alternative therapies. Sclareol (SCL), a labdane diterpenoid derived from Salvia sclarea, exhibits various biological activities, but its potential role in angiogenesis and pharmacokinetics after oral administration remain unexplored.<br><br>METHODS: Hypoxia-induced endothelial cells (ECs) were used as an in vitro model, while mouse oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were used as in vivo models. The pharmacokinetics of SCL in plasma, retina, and choroid were analyzed after oral administration in mice. Furthermore, the underlying mechanisms were elucidated through an integrative approach combining transcriptomics, metabolomics, network pharmacology, molecular docking, and molecular dynamics simulation.<br><br>RESULTS: SCL inhibited hypoxia-induced EC proliferation, permeability, migration, tube formation, sprouting, glycolysis, mitochondrial respiration, and oxidative stress by modulating the PI3K-AKT-FOXO1 pathway. Additionally, Oral administration of SCL significantly inhibited OIR and CNV progression in mice, demonstrating enhanced therapeutic efficacy when combined with intravitreal aflibercept (Eylea) injection.<br><br>CONCLUSION: SCL is a promising orally administered natural compound for ocular neovascularization, offering a potential alternative or adjunctive therapy to existing anti-VEGF treatments.},
}
@article {pmid40347367,
year = {2025},
author = {Hoshino, J and Matsumoto, H and Numaga, S and Nakamura, K and Akiyama, H},
title = {Two-year outcomes of treat-and-extend regimen with intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {4},
pages = {521-528},
pmid = {40347367},
issn = {1613-2246},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; *Visual Acuity ; Female ; Male ; Tomography, Optical Coherence ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Fluorescein Angiography ; Follow-Up Studies ; Aged, 80 and over ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Dose-Response Relationship, Drug ; Antibodies, Bispecific ; },
abstract = {PURPOSE: We previously reported 1-year outcomes of a treat-and-extend (TAE) regimen with intravitreal faricimab (IVF) for treatment-naïve neovascular age-related macular degeneration (nAMD). Herein, we evaluated the second-year results of this TAE regimen with IVF in eyes completing the first-year treatment.<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively studied 30 eyes with treatment-na&#xef;ve nAMD that had completed the initial year of treatment, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), total number of injections over 2 years, and intended injection interval at the last visit.<br><br>RESULTS: Twenty-five eyes completed the 2-year IVF treatment. There was no significant difference between pre-treatment and 2 years post-treatment BCVA. FT and CCT both showed significant reductions, maintained during the 2-year study period. The total number of injections was 10.1 &#xb1; 1.2 over the 2 years. The intended injection interval at the last visit was 13.0 &#xb1; 3.4 weeks. Of 5 eyes not completing 2 years of IVF treatment, 4 were switched to other anti-vascular endothelial growth factor (VEGF) agents due to persistent fluids despite IVF at 8-week intervals. In the remaining eye, IVF treatment was discontinued due to suspected faricimab-related intraocular inflammation.<br><br>CONCLUSIONS: The TAE regimen with IVF for treatment-na&#xef;ve nAMD was effective during a 2-year period for improving exudative changes and maintaining visual acuity. Although IVF was found to be a relatively safe treatment for nAMD, there were cases requiring a switch to other anti-VEGF agents due to inadequate fluid control effect.},
}
@article {pmid40347366,
year = {2025},
author = {Watanabe, Y and Koto, T and Takahashi, A and Mizuno, M and Ishida, T and Nakajima, K and Takeuchi, J and Yokoi, T and Nakayama, M and Okada, AA and Inoue, M and Kataoka, K},
title = {Factors predictive of treatment outcomes in submacular hemorrhage secondary to age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {5},
pages = {732-737},
pmid = {40347366},
issn = {1613-2246},
mesh = {Humans ; Retrospective Studies ; Female ; Male ; Tomography, Optical Coherence/methods ; Aged ; *Visual Acuity/physiology ; *Retinal Hemorrhage/etiology/diagnosis/therapy ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/complications/diagnosis/drug therapy ; Fluorescein Angiography/methods ; Treatment Outcome ; Fundus Oculi ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Ranibizumab/administration &amp; dosage ; *Endotamponade/methods ; *Macula Lutea/pathology ; },
abstract = {PURPOSE: To identify predictors for visual outcomes of eyes with submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: Clinical data from patients diagnosed with SMH secondary to nAMD and treated with pneumatic displacement were collected. SMH thickness was measured by optical coherence tomography (OCT) at baseline and 1 week. Possible factors associated with best-corrected visual acuity (BCVA) gain at 3 months were analyzed.<br><br>RESULTS: Fifty-six eyes of 56 patients (18 female/38 male; mean age, 77.8 &#xb1; 10.1 years) were analyzed; 34 were treatment-na&#xef;ve and 22 were previously treated with anti-vascular endothelial growth factor agents. Multivariable analysis showed that greater BCVA gain more than 0.3 logMAR at 3 months post-treatment was associated with being treatment-na&#xef;ve (odds ratio [OR], 34.30; 95% confidence interval [CI], 1.38-851.91; P = 0.031), thinner SMH thickness at 1 week after pneumatic displacement (OR, 0.38 per 50-unit increase; CI, 0.18-0.80; P = 0.011), and worse baseline BCVA (OR, 2.58 per 0.1-unit increase; CI, 1.31-5.07; P = 0.006), but not associated with age (OR, 0.50; 95% CI, 0.24-1.06), the time from onset to pneumatic displacement (OR, 1.04; 95%CI, 0.87-1.23), SMH thickness at baseline (OR, 0.92; 95%CI, 0.63-1.36), and the presence of subfoveal hemorrhagic PED (OR, 0.72; 95%CI, 0.08-6.84).<br><br>CONCLUSION: This study identifies novel factors predictive of visual outcomes for pneumatic displacement for SMH due to nAMD. The presence of residual SMH at 1 week following unsuccessful pneumatic displacement may warrant further intervention.},
}
@article {pmid40345486,
year = {2025},
author = {Contemori, G and Guenot, J and Cottereau, BR and Trotter, Y and Battaglini, L and Bertamini, M},
title = {Neural and perceptual adaptations in bilateral macular degeneration: an integrative review.},
journal = {Neuropsychologia},
volume = {215},
number = {},
pages = {109165},
doi = {10.1016/j.neuropsychologia.2025.109165},
pmid = {40345486},
issn = {1873-3514},
mesh = {Humans ; *Macular Degeneration/physiopathology/pathology ; *Adaptation, Physiological/physiology ; *Visual Perception/physiology ; *Visual Cortex/physiopathology ; Scotoma/physiopathology ; Animals ; },
abstract = {Bilateral age-related macular degeneration (AMD) results in central vision loss, affecting the fovea-associated cortical regions. This review examines neuroimaging and psychophysical evidence of spontaneous neural adaptation in acquired bilateral central scotoma. Early visual brain areas show reduced cortical thickness and axonal integrity due to postsynaptic (anterograde) degeneration. Contrary to animal models, evidence for spontaneous adaptation in the primary visual cortex (V1) is limited. Activity in the lesion projection zone (LPZ), previously seen as extensive cortical remapping, may result from non-retinotopic peripheral-to-foveal feedback, sharing substrates with healthy retinal feedforward processes. Preferred retinal loci (PRLs) are influenced more by location and task than by residual vision quality. Reduced lateral masking in the PRL may reflect decreased contrast sensitivity from retinal damage, rather than genuine adaptive mechanisms. Weakened crowding in the PRL is explained by transient adaptation in healthy subjects to artificial scotomas, not by long-term plasticity. Higher visual areas may show compensatory mechanisms enhancing complex tasks like symmetry, face, and motion discrimination. Leveraging spontaneous adaptation through perceptual learning-based treatments can preserve residual visual abilities. Because of limited evidence for spontaneous reorganization in AMD, behavioural training and emerging techniques are crucial for optimal treatment efficacy.},
}
@article {pmid40345358,
year = {2025},
author = {Eichenbaum, DA and Holekamp, N and Khanani, AM and Pieramici, D and Hershberger, V and Sheth, V and Brunstein, F and Ma, L and Zou, Y and Indjeian, VB and Dere, R and Maia, M and Hsu, JC and Gao, SS and Yaspan, B and Willis, JR and Wiley, H and Lai, P and Chen, H},
title = {Reply to Comment on Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {276},
number = {},
pages = {413-414},
doi = {10.1016/j.ajo.2025.04.042},
pmid = {40345358},
issn = {1879-1891},
}
@article {pmid40343605,
year = {2025},
author = {Zhao, X and Chen, X and Xin, X},
title = {MiR-6837-3p protected retinal epithelial cells from oxidative stress by targeting E2F6.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {183},
pmid = {40343605},
issn = {1573-2630},
mesh = {*MicroRNAs/genetics/biosynthesis ; *Oxidative Stress ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; Apoptosis ; *Gene Expression Regulation ; Cell Survival ; Hydrogen Peroxide ; *Macular Degeneration/metabolism/genetics/pathology ; Cell Movement ; Cells, Cultured ; Cell Proliferation ; Reactive Oxygen Species/metabolism ; Flow Cytometry ; Cell Line ; },
abstract = {AIM: The mechanism of age-related macular degeneration (AMD) is a complex illness that is not fully understood. Therefore, the aim of this study was to investigate the expression patterns of miR-6837-3p in retinal epithelial cells.<br><br>METHODS: H2O2 was used to treat ARPE-19 cells for 2, 4 and 6&#xa0;h to mimic the in vivo environment of AMD. MiR inhibitors and mimics were used to inhibit or overexpress miR-6837-3p in H2O2-treated ARPE-19 cells, respectively. Then, CCK8 assay, flow cytometry, and wound healing assays were conducted to assess the effects of miR-6837-3p on the behaviors of ARPE-19 cells, including cell growth, apoptosis, cycle progression, and migration. Finally, microRNA database prediction and luciferase reporter assays were used to demonstrate that miR-6837-3p targets the downstream gene E2F6.<br><br>RESULTS: H2O2 induced a decrease in cell viability and an increase in ROS levels in a time-dependent manner. Additionally, overexpression of miR-6837-3p increased cell viability and suppressed apoptosis in ARPE-19 cells treated with H2O2. Meanwhile, increased miR-6837-3p promoted cell cycle progression and cell migration of ARPE-19 cells. Finally, miR-6837-3p exerted anti-apoptosis and anti-oxidative stress effects by inhibiting the expression of E2F6 in ARPE-19 cells.<br><br>CONCLUSIONS: The MiR-6837-3p/E2F6 axis might be a target for the treatment of AMD to improve ARPE-19 cell function.},
}
@article {pmid40343286,
year = {2025},
author = {Zeng, B and Zhang, C and Liang, Y and Huang, J and Li, D and Liu, Z and Liao, H and Yang, T and Liu, M and Zou, C and Liu, D and Qin, B},
title = {Single-cell RNA sequencing highlights a significant retinal Müller glial population in dry age-related macular degeneration.},
journal = {iScience},
volume = {28},
number = {5},
pages = {112464},
pmid = {40343286},
issn = {2589-0042},
abstract = {The main challenge in dissecting the cells and pathways involved in the pathogenesis of age-related macular degeneration (AMD) is the highly heterogeneous and dynamic nature of the retinal microenvironment. This study aimed to describe the comprehensive landscape of the dry AMD (dAMD) model and identify the key cell cluster contributing to dAMD. We identified a subset of Müller cells that express high levels of Sox2, which play crucial roles in homeostasis and neuroprotection in both mouse models of AMD and patients with dAMD. Additionally, the number of Sox2[+] Müller cells decreased significantly during the progression of AMD, indicating these cells were damaged and underwent cell death. Interestingly, ferroptosis and apoptosis were identified as contributors to the damage of Sox2[+] Müller cells. Our findings are potentially valuable not only for advancing the current understanding of dAMD progression but also for the development of treatment strategies through the protection of Müller cells.},
}
@article {pmid40341462,
year = {2025},
author = {Noh, JH and Lee, MY and Yoo, C and Sung, KR and Kim, JM},
title = {Relationship Between Periodontitis and Open Angle Glaucoma: The Korea National Health and Nutrition Examination Survey.},
journal = {Journal of glaucoma},
volume = {34},
number = {8},
pages = {565-574},
doi = {10.1097/IJG.0000000000002584},
pmid = {40341462},
issn = {1536-481X},
mesh = {Humans ; Male ; Female ; Republic of Korea/epidemiology ; Middle Aged ; Nutrition Surveys ; *Glaucoma, Open-Angle/epidemiology ; *Periodontitis/epidemiology/complications ; Adult ; Aged ; Risk Factors ; Intraocular Pressure/physiology ; Periodontal Index ; Prevalence ; Cross-Sectional Studies ; Young Adult ; Odds Ratio ; },
abstract = {PRCIS: Using Korean National Health and Nutrition Examination Survey (KNHANES) data, this study reveals a significant association between periodontitis and open angle glaucoma.<br><br>PURPOSE: To investigate the relationship between periodontitis and open angle glaucoma.<br><br>METHODS: Data from 17,478 subjects in the KNHANES 2010-2011 were analyzed. We included 6215 subjects aged 19 years or older who underwent both dental and ophthalmological examinations that met International Society of Geographical and Epidemiological Ophthalmology criteria. Exclusions included ocular surgery (eg, refractive, cataract, retina), age-related macular degeneration, those who were pregnant or who were undergoing orthodontic treatment, and those with missing data. The final analysis included 3681 subjects. Periodontal disease was assessed using the Community Periodontal Index (CPI) developed by the WHO.<br><br>RESULTS: Of 3681 subjects, 197 (4.59%) had glaucoma and 3484 (95.41%) did not. Among the 197 glaucoma patients, 80 (39.48%) had periodontitis; among those without glaucoma, 892 (22.20%) had periodontitis (P <0.001). The periodontitis group was more likely to have glaucoma than the nonperiodontitis group [odds ratio (OR), 1.53; 95% CI, 1.06-2.22; adjusted for age, sex, DM, HTN, smoking rate, and drinking rate]. For those older than 40 years, the OR was 1.75 (95% CI, 1.18-2.61), and that for men was 1.65 (95% CI, 1.01-2.70). When comparing the group with and without periodontitis in DM patients, the OR was 2.70 (95% CI, 1.46-5.02).<br><br>CONCLUSION: This study shows a significant association between periodontitis and glaucoma, especially in patients aged 40 and older, men, and those with diabetes. Future follow-up studies are needed to elucidate the mechanism behind this association.},
}
@article {pmid40340707,
year = {2025},
author = {Hayakawa, R and Ishii, T and Fushimi, T and Kamei, Y and Yamaguchi, A and Sugimoto, K and Ashida, H and Akagawa, M},
title = {Luteolin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity through activation of Nrf2/Keap1 signaling.},
journal = {Free radical research},
volume = {59},
number = {4},
pages = {356-368},
doi = {10.1080/10715762.2025.2503832},
pmid = {40340707},
issn = {1029-2470},
mesh = {Humans ; *Luteolin/pharmacology ; *NF-E2-Related Factor 2/metabolism ; *Retinal Pigment Epithelium/drug effects/metabolism/radiation effects/pathology ; *Light/adverse effects ; *Kelch-Like ECH-Associated Protein 1/metabolism ; Signal Transduction/drug effects ; Oxidative Stress/drug effects ; Cell Line ; Apoptosis/drug effects ; Blue Light ; },
abstract = {Age-related macular degeneration (AMD), a serious physical and mental health problem worldwide, is the leading cause of irreversible, severe vision impairment and loss in older people. AMD is associated with multiple risk factors, many of which are closely linked to increased oxidative stress. Some studies have suggested that long-term and excessive exposure to blue light may be a potential risk factor for the development or progression of AMD. Recently, we demonstrated that blue light irradiation caused oxidative stress in all-trans-retinal (atRAL)-exposed human ARPE-19 retinal pigment epithelium cells by generating singlet oxygen ([1]O2), leading to apoptotic cell death. Luteolin, a flavonoid found in various edible plants, has been reported to possess divergent health-promoting properties including anti-oxidative and chemopreventive effects by up-regulating anti-oxidative and phase II detoxifying enzymes through activation of Keap1/Nrf2 signaling. Herein, we verified the cytoprotective action of luteolin against blue light irradiation using atRAL-exposed ARPE-19 cells. Our results established that luteolin effectively prevented blue light-induced apoptosis of ARPE-19 cells by mitigating oxidative stress. We also confirmed that luteolin suppressed intracellular accumulation of [1]O2 and formation of atRAL-derived lipofuscin by increased expression of heme oxygenase-1 and aldehyde dehydrogenase 1A1 through activation of Keap1/Nrf2 signaling. Furthermore, our data implied that the luteolin-provoked activation of Keap1/Nrf2 signaling might be due to covalent binding of luteolin o-quinone to the critical cysteinyl thiol in Keap1. The present results suggest that luteolin could be helpful in the prevention and amelioration of blue light-induced retinal degeneration, including AMD.},
}
@article {pmid40338383,
year = {2025},
author = {Bleidißel, N and Weichenberger, M and Maier, M and Spielberg, N and Feucht, N},
title = {Improved functional and morphological outcomes with faricimab in nAMD eyes with poor response to prior intravitreal anti-VEGF therapy.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {177},
pmid = {40338383},
issn = {1573-2630},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged, 80 and over ; *Antibodies, Bispecific/administration &amp; dosage ; Treatment Outcome ; Fluorescein Angiography ; Follow-Up Studies ; Ranibizumab/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor ; Middle Aged ; Fundus Oculi ; Recombinant Fusion Proteins ; },
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a major cause of vision loss in older adults. While anti-VEGF therapies have improved management by suppressing abnormal blood vessel growth, a substantial subset of patients show poor functional as well as morphological responses and require frequent injections. Faricimab (Vabysmo®), a bispecific inhibitor targeting VEGF-A and angiopoietin-2 (Ang-2), has shown promise in achieving more durable disease control.<br><br>METHODS: This retrospective study included 48 eyes from 47 nAMD patients previously treated with ranibizumab or aflibercept, who were switched to faricimab due to poor treatment response. Evaluations occurred at four time points, assessing best-corrected visual acuity (BCVA), intraretinal (IRF) and subretinal fluid (SRF), subretinal pigment epithelium fluid and fibrosis, central subfield thickness (CST), and central subfield volume (CSV) using spectral-domain OCT. Dosing intervals and patient-reported outcomes were also recorded.<br><br>RESULTS: BCVA improved consistently, with mean logMAR improving from 0.54 to 0.40, reflecting a gain of 1.4 Snellen lines. Dosing intervals extended from a median of 5 to 8&#xa0;weeks, with over one-third of eyes reaching intervals of 10&#xa0;weeks or more. Significant reductions in IRF, SRF, CST as well as CSV were observed (p&#x2009;<&#x2009;0.05) with a quarter of eyes showing no intra- or subretinal fluid at the fourth faricimab injection. Three patients were switched back to their previous anti-VEGF treatment due to a decline in BCVA.<br><br>DISCUSSION: The findings suggest Faricimab as an effective option for nAMD patients who respond inadequately to prior anti-VEGF therapies, offering both functional and anatomical improvements. Extended intervals reduce treatment burden, indicating faricimab's potential to enhance disease control and patient quality of life in real-world settings.},
}
@article {pmid40337864,
year = {2025},
author = {Li, W and Zhang, Y and Zhu, H and Su, N and Sun, R and Mao, X and Yang, Q and Yuan, S},
title = {CAVIN3 deficiency promotes vascular normalization in ocular neovascular disease via ERK/JAG1 signaling pathway.},
journal = {JCI insight},
volume = {10},
number = {9},
pages = {},
pmid = {40337864},
issn = {2379-3708},
mesh = {Animals ; Mice ; Humans ; *Choroidal Neovascularization/metabolism/pathology/genetics ; Disease Models, Animal ; Endothelial Cells/metabolism ; *Jagged-1 Protein/metabolism/genetics ; Signal Transduction ; MAP Kinase Signaling System ; Macular Degeneration/metabolism/pathology ; Diabetic Retinopathy/metabolism/pathology/genetics ; Male ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/metabolism/pathology ; *Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Female ; *Neovascularization, Pathologic/metabolism ; Choroid/pathology ; },
abstract = {Multiple members of the caveolae-associated protein (Cavin) family are implicated in angiogenesis. However, the specific role of CAVIN3 in pathological angiogenesis within the eye remains unclear. The present study demonstrated that CAVIN3 knockdown in endothelial cells (ECs) promoted vascular normalization in ocular pathological neovascularization. Elevated CAVIN3 expression was observed in the ECs of retinal pigment epithelium/choroid complexes from patients with neovascular age-related macular degeneration and fibrovascular membranes from patients with proliferative diabetic retinopathy. Additionally, upregulated Cavin3 expression was detected in laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) mouse models. In both OIR and CNV mice, Cavin3 knockdown inhibited pathological neovascularization. Cavin3 deficiency further disrupted EC proliferation and vascular sprouting, thereby promoting vascular normalization by partially restoring microenvironmental hypoxia and reestablishing pericyte-EC interactions. Mechanistically, we demonstrated that zinc finger E-box-binding homeobox 1 (ZEB1) regulated CAVIN3 transcription in ECs under hypoxic conditions. CAVIN3 deficiency modulated pathological vascularization by inhibiting ERK phosphorylation, which downregulated jagged 1 (JAG1) expression. Conclusively, this study elucidated the protective role of endothelial CAVIN3 deficiency in pathological neovascularization models, addressing a gap in understanding the regulatory role of Cavins in angiogenesis. These findings suggested a therapeutic direction for ocular neovascular diseases.},
}
@article {pmid40335681,
year = {2025},
author = {Yu, J and Zhang, Y and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association between leukocyte telomere length and incident glaucoma: A prospective UK biobank study.},
journal = {Eye (London, England)},
volume = {39},
number = {11},
pages = {2176-2182},
pmid = {40335681},
issn = {1476-5454},
mesh = {Humans ; Male ; Female ; *Leukocytes/metabolism/pathology ; Prospective Studies ; United Kingdom/epidemiology ; Middle Aged ; *Glaucoma/epidemiology/genetics ; Aged ; Incidence ; Biological Specimen Banks ; *Telomere/genetics ; Risk Factors ; Intraocular Pressure/physiology ; Follow-Up Studies ; UK Biobank ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) has been associated with various diseases, including age-related eye diseases such as cataract and age-related macular degeneration. However, the role of LTL in the longitudinal development of glaucoma is still unknown. Here we prospectively evaluate the association of LTL with glaucoma incidence and related traits, in the UK Biobank cohort.<br><br>METHODS: The study cohort included 419,603 participants with complete baseline data for glaucoma analyses. Multivariable Cox proportional hazards models were used to evaluate the association between LTL and the risk of glaucoma incidence, and multivariable linear regression was employed to test the association between LTL and glaucoma-related traits.<br><br>RESULTS: During a 13.58-year follow-up period, 7385 (1.76%) participants developed glaucoma. No association between LTL and incident glaucoma was found in either Model 1 (adjusted for age, sex, ethnicity and the ancestry components; HR&#x2009;=&#x2009;1.011, 95% CI: 0.990-1.033; P&#x2009;=&#x2009;0.311), or Model 2 (additionally adjusted for smoking status, alcohol consumption, body mass index, systolic blood pressure, education level, Townsend Deprivation Index, polygenic risk score for glaucoma, and history of diabetes and cardiovascular diseases; HR&#x2009;=&#x2009;1.010, 95% CI: 0.988-1.032; P&#x2009;=&#x2009;0.367). Non-significant associations were also observed for glaucoma-related traits, including the retinal nerve fibre layer, ganglion cell-inner plexiform layer, and intraocular pressure with LTL (all P-values&#x2009;>&#x2009;0.05), but LTL was associated with a slightly increased vertical cup-to-disc ratio (P&#x2009;=&#x2009;0.009).<br><br>CONCLUSIONS: This study suggested that LTL is not a major biomarker for incident glaucoma in the UK Biobank population. Further studies in different populations are warranted.},
}
@article {pmid40333806,
year = {2025},
author = {Chen, MY and Du, J and Do, BK and Ali, MH},
title = {Comparing visual outcomes of nAMD treatment during and after the COVID-19 restrictions period.},
journal = {PloS one},
volume = {20},
number = {5},
pages = {e0323253},
pmid = {40333806},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Male ; Female ; Aged ; Retrospective Studies ; Visual Acuity/drug effects ; Treatment Outcome ; Aged, 80 and over ; SARS-CoV-2 ; Middle Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Bevacizumab/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {MAIN OBJECTIVE: Compare treatment outcomes of newly diagnosed neovascular age-related macular degeneration (nAMD) during and after the COVID-19 restrictions.<br><br>METHODS: This retrospective study at the Retina Group of Washington analyzed nAMD patients treated with anti-VEGF therapy with&#x2009;&#x2265;&#x2009;12 months of follow-up. Two groups were identified: 258 subjects diagnosed between March 2020-March 2022 (Group 1) and 376 subjects diagnosed after (Group 2). Primary outcomes were 12-month and final best-corrected visual acuity (BCVA), and number of injections in the first 12 months.<br><br>RESULTS: Initial mean BCVA was 20/71 and 20/68 in Group 1 and Group 2, with median BCVA of 20/60 and 20/50, respectively. At 12 months, mean BCVA improved to 20/65 and 20/54 in Group 1 and Group 2, respectively (p&#x2009;=&#x2009;0.086). Final mean BCVA was 20/76 for Group 1 and 20/58 for Group 2 (p&#x2009;=&#x2009;0.010). The mean change in LogMAR BCVA from the time of conversion to last follow-up was&#x2009;+&#x2009;0.03 for Group 1 and -0.08 for Group 2 (p&#x2009;=&#x2009;0.007). Group 1 had fewer injections in the first year of therapy (8.67 vs. 9.21, p&#x2009;=&#x2009;0.004). 38.8% of Group 1 reached BCVA &#x2265;20/40 at 12 months, versus 48.9% for Group 2 (p&#x2009;=&#x2009;0.011).<br><br>CONCLUSION: Patients diagnosed during the COVID-19 restrictions period had worse visual outcomes than those diagnosed thereafter. Multiple factors, including, but not limited to reduced treatment frequency, likely contributed to worse visual outcomes.},
}
@article {pmid40332908,
year = {2025},
author = {Machida, A and Suzuki, K and Nakayama, T and Miyagi, S and Maekawa, Y and Murakami, R and Uematsu, M and Kitaoka, T and Oishi, A},
title = {Glucagon-Like Peptide 1 Receptor Agonist Stimulation Inhibits Laser-Induced Choroidal Neovascularization by Suppressing Intraocular Inflammation.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {5},
pages = {15},
pmid = {40332908},
issn = {1552-5783},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/prevention &amp; control/drug therapy/etiology ; Mice, Inbred C57BL ; Mice ; *Glucagon-Like Peptide-1 Receptor Agonists ; Disease Models, Animal ; Intravitreal Injections ; *Liraglutide/therapeutic use/pharmacology ; Glucagon-Like Peptide-1 Receptor/metabolism ; *Inflammation/prevention &amp; control/metabolism ; Laser Coagulation/adverse effects ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Male ; Immunohistochemistry ; Cytokines/metabolism ; Real-Time Polymerase Chain Reaction ; },
abstract = {PURPOSE: The glucagon-like peptide-1 receptor (GLP-1R), a diabetes therapy target, is expressed in multiple organs and is associated with neuroprotective, anti-inflammatory, and antitumor effects, particularly in cardiac and cerebral tissues. Although GLP-1's role in diabetic and ischemic retinopathies is well-studied, its influence on choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) remains unclear. This study explored the effects of GLP-1 on CNV using a laser-induced mouse model.<br><br>METHODS: The anti-angiogenic effects of GLP-1 were tested using ex vivo sprouting assays in 3-week-old C57BL/6J mice. In 6-week-old mice, GLP-1R localization in laser-induced CNV lesions was analyzed via immunohistochemistry. Liraglutide, a GLP-1R agonist, was administered subcutaneously for 7 days or by single intravitreal injection post-laser. Eyeballs collected on days 1 to 7 post-laser were analyzed using RT-qPCR for GLP-1R expression and inflammatory cytokines.<br><br>RESULTS: GLP-1R-positive cells were detected in CNV lesions and were expressed in Iba-1-positive activated microglia or macrophages. They also expressed in abnormal retinal pigment epithelial cells and surrounding normal endothelial cells. NOD-like receptor protein 3 (NLRP3) inflammasome signaling was observed near CNV. Liraglutide inhibited angiogenesis in ex vivo assays and significantly reduced CNV formation with both subcutaneous and intravitreal administration. Additionally, Liraglutide inhibited expression of NLRP3, IL-1&#x3b2;, IL-6, and TNF expression compared with healthy controls. Intravitreal GLP-1R antagonist reduced subcutaneous effects.<br><br>CONCLUSIONS: Liraglutide suppresses CNV formation, likely via NLRP3 inflammasome inhibition. Intraocular GLP-1R appears to mediate anti-CNV effects, supporting GLP-1R agonists as potential adjunctive therapy for exudative AMD and warranting further investigation into its safety and clinical feasibility.},
}
@article {pmid40332529,
year = {2025},
author = {Moshtaghion, SMM and Locri, F and Reyes, AP and Plastino, F and Kvanta, A and Morillo-Sanchez, MJ and Rodríguez-de-la-Rúa, E and Gutierrez-Sanchez, E and Montero-Sánchez, A and Lucena-Padros, H and André, H and Díaz-Corrales, FJ},
title = {VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples.},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
pmid = {40332529},
issn = {1422-0067},
support = {PI17/01026, P-FIS: 21/00087//Instituto de Salud Carlos III and the Fondo Europeo de Desarrollo Regional/ ; C2-0009-2020//Junta de Andaluc&#xed;a, Programa Nicol&#xe1;s Monardes/ ; },
mesh = {Animals ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; Humans ; Biomarkers/metabolism ; Mice ; Female ; Disease Models, Animal ; *Macular Degeneration/metabolism/pathology ; *Tears/metabolism ; Male ; Aged ; Retinal Pigment Epithelium/metabolism ; Tomography, Optical Coherence ; Choroidal Neovascularization/metabolism ; Choroid/metabolism ; STAT3 Transcription Factor/metabolism ; Aged, 80 and over ; NF-kappa B/metabolism ; Middle Aged ; },
abstract = {Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid-retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid-RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization.},
}
@article {pmid40332382,
year = {2025},
author = {Liu, X and Ni, Z and Zhang, J and Lin, X and Wu, C and Wu, Y and Dong, L and Zhang, Z and Chi, ZL},
title = {The Protective Role of DUSP4 in Retinal Pigment Epithelium Senescence and Degeneration.},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
pmid = {40332382},
issn = {1422-0067},
support = {82271114//National Natural Science Foundation of China/ ; LZ22H120001//the Natural Science Foundation of Zhejiang Province/ ; KYYW202227//research expenses of Wenzhou Medical University/ ; },
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Dual-Specificity Phosphatases/metabolism/genetics ; *Cellular Senescence/genetics ; *Mitogen-Activated Protein Kinase Phosphatases/metabolism/genetics ; Mice ; *Macular Degeneration/metabolism/pathology/genetics ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction ; Mice, Knockout ; NF-kappa B/metabolism ; Cell Line ; Protein Tyrosine Phosphatases ; },
abstract = {The retinal pigment epithelium (RPE) serves as a critical guardian of subretinal homeostasis, with its dysfunction implicated in major retinal pathologies, including age-related macular degeneration (AMD) and retinitis pigmentosa. While cellular senescence has emerged as a key driver of RPE degeneration, the molecular mechanisms underlying this process remain incompletely defined. Emerging evidence implicates dual-specificity phosphatase 4 (DUSP4) in cellular stress responses through its antioxidant and anti-inflammatory capacities, yet its role in RPE pathophysiology remains unexplored. Our study reveals a compensatory increase in DUSP4 expression during AMD-associated RPE senescence. To functionally characterize this observation, we knocked down DUSP4 in the RPE of mice via subretinal injection of AAV-shDUSP4. In a sodium iodate-induced dry AMD model, mice with DUSP4 knockdown presented more severe visual impairment than control mice did. To further investigate the molecular mechanism, stable DUSP4-knockout cell lines were constructed via CRISPR/Cas9 technology. The high expression of senescence markers in the DUSP4-knockout cell lines was reversed by DUSP4 overexpression. Furthermore, DUSP4 coordinates the modulation of cell cycle, stress response, and pro-inflammatory signaling by inhibiting the p53, p38, and NF-kB pathways. These findings establish DUSP4 as a multi-functional regulator of RPE senescence. Our work not only elucidates a novel DUSP4-dependent mechanism in AMD pathogenesis but also highlights its therapeutic potential for preserving RPE function in AMD.},
}
@article {pmid40332323,
year = {2025},
author = {Tsou, SH and Luo, KS and Huang, CN and Kornelius, E and Cheng, IT and Hung, HC and Hung, YC and Lin, CL and Hsu, MY},
title = {Liraglutide Attenuates FFA-Induced Retinal Pigment Epithelium Dysfunction via AMPK Activation and Lipid Homeostasis Regulation in ARPE-19 Cells.},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
pmid = {40332323},
issn = {1422-0067},
support = {CSH-2025-C-049//Chung Shan Medical University Hospital/ ; 112-2320-B-040-003-MY3//National Science and Technology Council of Taiwan/ ; 111-2314-B-040-029-MY3//National Science and Technology Council of Taiwan/ ; 111-2320-B-040-017-MY3//National Science and Technology Council of Taiwan/ ; 113-2314-B-040-009//National Science and Technology Council of Taiwan/ ; NCHU-CSMU-11305//the bilateral project from National Chung Hsing University and Chung Shan Medical University/ ; },
mesh = {*Liraglutide/pharmacology ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Humans ; *AMP-Activated Protein Kinases/metabolism ; Oxidative Stress/drug effects ; *Lipid Metabolism/drug effects ; Cell Line ; Homeostasis/drug effects ; *Fatty Acids, Nonesterified/pharmacology ; Macular Degeneration/metabolism/drug therapy/pathology ; Epithelial-Mesenchymal Transition/drug effects ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, and it is characterized by oxidative stress, lipid dysregulation, and dysfunction of the retinal pigment epithelium (RPE). A hallmark of AMD is the presence of drusen, extracellular deposits rich in lipids, proteins, and cellular debris, which are secreted by the RPE. These deposits impair RPE function, promote chronic inflammation, and accelerate disease progression. Despite advancements in understanding AMD pathogenesis, therapeutic strategies targeting lipid dysregulation and oxidative damage in RPE cells remain limited. This study evaluated the effects of liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on free fatty acid (FFA)-induced damage in ARPE-19 cells, a widely used in vitro model of RPE dysfunction. FFA treatment induced lipid droplet accumulation, oxidative stress, and epithelial-mesenchymal transition (EMT), which are processes implicated in AMD progression. Liraglutide significantly reduced lipid droplet accumulation, mitigated oxidative stress, and suppressed EMT, as demonstrated by high-content imaging, immunocytochemistry, and molecular assays. Mechanistic analyses revealed that liraglutide activates AMP-activated protein kinase (AMPK), enhancing lipophagy and restoring lipid homeostasis. Furthermore, liraglutide influenced exosome secretion, altering paracrine signaling and reducing EMT markers in neighboring cells. These findings underscore liraglutide's potential to address critical mechanisms underlying AMD pathogenesis, including lipid dysregulation, oxidative stress, and EMT. This study provides foundational evidence supporting the development of GLP-1 receptor agonists as targeted therapies for AMD.},
}
@article {pmid40331961,
year = {2025},
author = {Ochoa Hernández, ME and Lewis-Luján, LM and Burboa Zazueta, MG and Del Castillo Castro, T and De La Re Vega, E and Gálvez-Ruiz, JC and Trujillo-López, S and López Torres, MA and Iloki-Assanga, SB},
title = {Role of Oxidative Stress and Inflammation in Age Related Macular Degeneration: Insights into the Retinal Pigment Epithelium (RPE).},
journal = {International journal of molecular sciences},
volume = {26},
number = {8},
pages = {},
pmid = {40331961},
issn = {1422-0067},
mesh = {Humans ; *Macular Degeneration/metabolism/pathology/etiology ; *Oxidative Stress ; *Retinal Pigment Epithelium/metabolism/pathology ; *Inflammation/metabolism/pathology ; Animals ; Reactive Oxygen Species/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide, characterized by the accumulation of extracellular drusen deposits within the macula. The pathogenesis of AMD is multifactorial, involving oxidative stress, chronic inflammation, immune system dysregulation, and genetic predisposition. A key contributor to disease progression is the excessive accumulation of reactive oxygen species (ROS), which damage retinal pigment epithelium (RPE) cells and disrupt cellular homeostasis. Additionally, immunosenescence and chronic low-grade inflammation exacerbate AMD pathology, further impairing retinal integrity. Despite ongoing research, effective therapeutic options remain limited, and there is no definitive cure for AMD. This review explores the intricate molecular mechanisms underlying AMD, including the role of oxidative stress, chronic inflammation, and genetic factors in RPE dysfunction. Furthermore, we highlight potential therapeutic strategies targeting these pathways, as well as the emerging role of bioinformatics and artificial intelligence in AMD diagnosis and treatment development. By improving our understanding of AMD pathophysiology, we can advance the search for novel therapeutic interventions and preventative strategies.},
}
@article {pmid40330967,
year = {2025},
author = {Ciszewski, P and Drelichowska, A and Pikor, D and Wiśniewska, E and Azierski, M},
title = {Innovative technologies for the treatment of dry age-related macular degeneration (AMD) - modern therapeutic perspectives and their future.},
journal = {Romanian journal of ophthalmology},
volume = {69},
number = {1},
pages = {10-16},
pmid = {40330967},
issn = {2501-2533},
mesh = {Humans ; *Genetic Therapy/methods ; *Quality of Life ; *Geographic Atrophy/therapy ; Tissue Engineering/methods ; },
abstract = {PURPOSE: This review explores modern therapeutic options for the dry form of age-related macular degeneration (AMD), a condition representing one of the most significant challenges in ophthalmology due to its progressive nature and lack of effective treatment. The study discusses innovative approaches, evaluates available methods, and examines the potential of emerging technologies to improve patients' quality of life.<br><br>METHODS: A comprehensive review of current literature was conducted, being focused on therapies for dry AMD, including classical methods such as AREDS/AREDS2 supplementation, molecularly targeted drugs, gene therapy, cell transplants, tissue engineering, nanotechnology, and light-based therapies. Emerging tools leveraging artificial intelligence for personalized treatment and predictive modeling were also evaluated.<br><br>RESULTS: AREDS/AREDS2 therapies effectively slow disease progression but cannot reverse retinal damage. Advances include molecularly targeted therapies (Pegcetacoplan, Avacincaptad Pegol) that reduce inflammation, gene therapy (HMR59) protecting RPE cells, and mitochondria-targeted drugs (SS-31) mitigating oxidative stress. Using scaffolds, nanoparticles, tissue engineering, and nanotechnology enhances RPE regeneration and drug delivery. Light-based therapies (LLLT, adaptive phototherapy) improve mitochondrial function, while AI aids in predicting disease progression and personalizing treatment.<br><br>CONCLUSIONS: Modern therapeutic approaches for dry AMD provide promising avenues to slow disease progression and protect vision. However, further clinical trials are needed to optimize these strategies, assess long-term outcomes, and expand patient access to effective treatments. These advancements have the potential to significantly improve the quality of life for individuals affected by dry AMD.},
}
@article {pmid40330498,
year = {2024},
author = {Gong, Q and Hu, L and Liu, G and Yin, X and Zhao, X and Li, Q and Li, Y and Sun, Y and Zhou, Y and Guo, C and Du, Z},
title = {WTAP-mediated N6-methyladenosine mRNA methylation regulates laser-induced macular neovascularization.},
journal = {Molecular vision},
volume = {30},
number = {},
pages = {336-347},
pmid = {40330498},
issn = {1090-0535},
mesh = {Animals ; *Adenosine/analogs &amp; derivatives/metabolism/genetics ; *RNA, Messenger/metabolism/genetics ; Methylation ; Mice ; Disease Models, Animal ; beta Catenin/metabolism/genetics ; Mice, Inbred C57BL ; *Retinal Neovascularization/metabolism/genetics/pathology ; *Choroidal Neovascularization/metabolism/genetics/pathology ; Lasers/adverse effects ; Humans ; *Macular Degeneration/genetics/metabolism/pathology ; RNA, Small Interfering/genetics ; Male ; *Cell Cycle Proteins/metabolism/genetics ; Cell Proliferation ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is now a major cause of central vision loss in older adults worldwide. The primary characteristic of nAMD is the formation of macular neovascularization (MNV), which is a pathologic form of angiogenesis. Epigenetics plays a role in multiple pathological physiologic processes. N6-methyladenosine (m6A) modification is the most common, abundant, and reversible modification in eukaryotic mRNAs, and it plays a role in various pathological angiogenesis processes. This study intends to reveal the expression and functions of m6A during the macular neovascularization (MNV) process.<br><br>METHODS: A laser-induced MNV mouse model was used in this study. m6A quantitative analysis was performed to detect the expression of m6A. Subsequently, the expression of various m6A writers and erasers was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Immunohistochemistry was used to detect Wilms' tumor 1-associating protein (WTAP) expression in the MNV lesions. Intravitreal injection of WTAP siRNA in MNV mice to silence the WTAP gene. Hematoxylin and eosin (H&amp;E) were used to determine the thickness and length of the MNV. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were examined to measure the leakage area of the MNV. Proliferating cell nuclear antigen (PCNA) expression was detected with a western blot. The mRNA and protein levels of &#x3b2;-catenin were tested with qRT-PCR and western blot.<br><br>RESULTS: We found increased m6A modification levels after laser induction compared with the normal control group. Subsequently, the expression of various m6A writers and erasers was detected. The results showed that WTAP increased in the MNV model in mice. After the injection of WTAP siRNA into the vitreous body, the expression of WTAP significantly decreased, subsequently decreasing the m6A modification levels. The width, breadth, and leakage area of MNV damage markedly decreased, and endothelial cell proliferation was inhibited. After laser-induced MNV, the expression of &#x3b2;-catenin increased, and that of &#x3b2;-catenin significantly decreased after WTAP knockout.<br><br>CONCLUSIONS: In conclusion, this study suggests that WTAP-mediated m6A methylation can regulate pathological angiogenesis during MNV and that WTAP may participate in the formation of MNV through the wingless-related integration site (Wnt) pathway. WTAP may be a potential target for MNV treatment.},
}
@article {pmid40330313,
year = {2025},
author = {Almpanidou, S and Vachliotis, ID and Goulas, A and Polyzos, SA},
title = {The potential role of adipokines and hepatokines in age-related ocular diseases.},
journal = {Metabolism open},
volume = {26},
number = {},
pages = {100365},
pmid = {40330313},
issn = {2589-9368},
abstract = {Age-related ocular diseases, including diabetic retinopathy (DR), age-related macular degeneration (AMD), cataract and glaucoma may lead to visual impairment and even to blindness. Metabolic diseases, such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as potential risk factors of age-related ocular diseases, especially DR. Visceral adiposity has been associated with increased risk of DR and AMD in most clinical studies, although body mass index has to-date provided conflicting association with DR and AMD. In addition, obesity is recognized as a risk factor of cataract and glaucoma. Similarly to obesity, MASLD appears to be associated with DR in patients with type 1 diabetes mellitus, but probably not in those with type 2 diabetes mellitus. A potential positive association between MASLD and AMD, glaucoma and cataract is supported by limited evidence to-date, thus needing further investigation. Altered secretion patterns of adipokines (adiponectin, leptin, lipocalin-2, resistin) and hepatokines [adropin, fetuin-A, fibroblast growth factor (FGF)-21, retinol binding protein (RBP)-4] seem to disrupt ocular homeostasis and contribute to the development of age-related ocular diseases in the context of obesity and MASLD. In this regard, novel adipokine-based and hepatokine-based therapies may be added to the treatment options for ocular diseases in the future. This narrative review aimed to summarize evidence on the interconnection of obesity and MASLD with age-related ocular diseases, with a specific focus on the roles of adipokines and hepatokines as mediators of these potential associations.},
}
@article {pmid40329608,
year = {2025},
author = {Çalış Karanfil, F and Özmert, E},
title = {Evaluation of the macula pigment optical density by a psychophysical test in dry age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {35},
number = {5},
pages = {1675-1685},
doi = {10.1177/11206721251339507},
pmid = {40329608},
issn = {1724-6016},
mesh = {Humans ; Male ; Female ; Prospective Studies ; *Macular Pigment/metabolism ; Aged ; Lutein/administration &amp; dosage/metabolism ; Middle Aged ; Zeaxanthins ; *Geographic Atrophy/metabolism/diagnosis/drug therapy/physiopathology ; Fluorescein Angiography ; Visual Field Tests ; *Macula Lutea/metabolism ; Psychophysics ; Visual Acuity/physiology ; Visual Fields/physiology ; Xanthophylls/administration &amp; dosage ; Aged, 80 and over ; },
abstract = {PurposeTo evaluate the macular pigment optical density (MPOD) in dry age-related macular degeneration (AMD).MethodsThis prospective study included 68 dry AMD patients and, as the control group, 91 healthy volunteers. Age, gender, family history, smoking, alcohol, hypertension, hyperlipidemia, height, weight, dietary lutein intake, and use of lutein-zeaxanthin (L-Z) were questioned. Full ophthalmic examination was performed. Color fundus photography and fundus autofluorescence (FAF) images were recorded. MPOD was measured by color perimetry (CP) every 3 months for 9 months in the dry AMD group, and 1 time at the beginning of the study in the control group. 6 mg/day lutein or 10 mg/day L and 2 mg/day Z were started in non-users.ResultsSmoking, obesity, family history, light iris color, and hyperlipidemia were seen more frequently in the AMD group. Average MPOD values in the AMD group were; 3.69 ± 1.82 (baseline), 4.74 ± 1.29 (3rd month), 4.99 ± 1.27 (6th month), and 5.02 ± 1.35 (9th month) dB, respectively. In the control group, the average MPOD was 4.97 ± 1.27 dB. At the baseline, the MPOD of the AMD group was significantly lower than the control group. Smoking, obesity, poor dietary lutein intake, light iris color, and hyperlipidemia were associated with low MPOD.DiscussionThe relationship between MPOD and AMD is controversial in the literature. Low MPOD and AMD may be related depending on our results. Quit smoking, and having a rich dietary L-Z intake are important for preventing AMD progression. The results of the CP are consistent with the other psychophysical tests.},
}
@article {pmid40329243,
year = {2025},
author = {Abualhasan, H and Beshtawi, IM and Noor, M and Mustafa, O and Hantoli, S},
title = {Predictive factors for adherence to intravitreal anti-vascular endothelial growth factor therapy in Palestinian patients with diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration: a retrospective cohort study.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {268},
pmid = {40329243},
issn = {1471-2415},
mesh = {Humans ; Female ; Male ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Retinal Vein Occlusion/drug therapy/ethnology ; *Diabetic Retinopathy/drug therapy/ethnology ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; *Macular Degeneration/drug therapy/ethnology ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Arabs ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; Visual Acuity ; Aptamers, Nucleotide ; Aged, 80 and over ; },
abstract = {BACKGROUND: The burden of retinal vascular and degenerative diseases on patients and healthcare systems can be significant if patients do not complete scheduled intravitreal injections. This study aimed to identify the factors that influence adherence with follow-up injections in patients with diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion receiving intravitreal injections of anti-vascular endothelial growth factor treatment.<br><br>METHODS: This study utilized data from patients who received intravitreal anti-vascular endothelial growth factor injections between 2022 and 2023 at An-Najah National University Hospital. Patient information, such as demographic information, number of injections administered, and details of follow-up visits, was obtained from the hospital's electronic records. When electronic records lacked certain information, patients or their relatives were contacted to provide the missing data. Data entry and analysis were performed using chi-square tests and the Statistical Package for Social Sciences. A p-value&#x2009;&#x2264;&#x2009;0.05 indicated statistical significance.<br><br>RESULTS: A total of 107 patients, 43 (40.2%) were adherent, while 64 (59.8%) were non-adherent. Sex was significantly associated with adherence (P&#x2009;=&#x2009;0.035), with females more likely to adhere. Planned number of injections correlated with adherence (P&#x2009;=&#x2009;0.004), as those receiving fewer injections were more adherent. Cost problems negatively impacted adherence (P&#x2009;=&#x2009;0.016), with non-adherent patients more frequently reporting financial barriers. Positive patient expectations for vision improvement were strongly associated with adherence (P&#x2009;=&#x2009;0.003). Mobility problems influenced adherence (P&#x2009;=&#x2009;0.049), as those without mobility issues adhered more. Physical assistance from relatives significantly improved adherence (P&#x2009;=&#x2009;0.036). Factors not significantly influencing adherence included comorbidities, education level, and insurance status.<br><br>CONCLUSION: Our study revealed that 60% of patients did not adhere to intravitreal anti-vascular endothelial growth factor treatment injections. Factors influencing adherence included the planned number of injections, cost problems, indication for injections, sex, need for physical assistance, and mobility problems. It is crucial to increase awareness of these factors to prevent complications such as blindness. Raising awareness could lead to improved adherence rates, better treatment outcomes, and positive impacts on patient and community health.},
}
@article {pmid40329206,
year = {2025},
author = {Zhang, L and Luo, Y},
title = {Correlation analysis between OCT evaluation and postoperative visual prognosis of patients with age-related macular degeneration complicated with cataract.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {266},
pmid = {40329206},
issn = {1471-2415},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Retrospective Studies ; *Visual Acuity/physiology ; Aged ; Prognosis ; *Cataract/complications/physiopathology ; Aged, 80 and over ; *Macular Degeneration/complications/physiopathology/surgery ; Postoperative Period ; ROC Curve ; Middle Aged ; Phacoemulsification ; *Cataract Extraction ; },
abstract = {OBJECTIVE: To explore the correlation between optical coherence tomography (OCT) evaluations and postoperative visual prognosis in individuals with AMD complicated with cataract, and to investigate the clinical applications of these evaluations for predicting visual outcomes.<br><br>METHODS: We retrospectively analyzed the clinical data of 132 individuals (132 eyes) with AMD complicated by cataract, admitted to our hospital from April 2022 to January 2024. All patients underwent surgical treatment and were categorized into two groups based on their visual prognosis after 6 months: the "good prognosis (GP)" group (best corrected visual acuity decrease < 0.1 logMAR) and the "poor prognosis (PP)" group (best corrected visual acuity decrease &#x2265; 0.1 logMAR). We evaluated OCT parameters including central retinal thickness (CRT), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and total average macular thickness (TR). Pearson correlation analysis was employed to assess the relationship between these OCT parameters and postoperative visual outcomes. Additionally, receiver operating characteristic (ROC) were used to calculate the predictive value of OCT measurements for identifying poor postoperative visual prognosis in this patient cohort.<br><br>RESULTS: Preoperative OCT results showed significantly higher values for CMT, CRT, TR, and SFCT in the PP group compared to the GP group (P < 0.05). Pearson correlation analysis revealed a positive association between postoperative visual acuity and these OCT parameters. Logistic regression modeling identified CMT, CRT, TR, and SFCT as key predictors of poor visual prognosis in AMD patients with cataract. ROC analysis showed that combining these parameters improved the prediction accuracy, with an area under the curve (AUC) of 0.993, sensitivity of 99.87%, and specificity of 95.30%, which were significantly higher compared to single-index evaluations (P < 0.05).<br><br>CONCLUSION: CMT, CRT, TR, SFCT are obviously related to the postoperative visual prognosis in patients with AMD complicated by cataract. The combined evaluation of these OCT parameters demonstrates high predictive efficiency for poor postoperative visual prognosis and can serve as an important assessment index for evaluating the postoperative visual prognosis in this patient population.},
}
@article {pmid40329091,
year = {2025},
author = {Scampoli, A and Carlà, MM and Grieco, G and Governatori, L and Catalani, R and Rizzo, S and Caporossi, T},
title = {One-year functional and structural results of faricimab for treatment-naïve neovascular age related macular degeneration: An OCT angiography study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {8},
pages = {2219-2226},
pmid = {40329091},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Female ; Male ; *Visual Acuity ; Prospective Studies ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Follow-Up Studies ; Aged ; Fundus Oculi ; Treatment Outcome ; *Macula Lutea/pathology ; Aged, 80 and over ; Time Factors ; Dose-Response Relationship, Drug ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To explore the 1-year functional and anatomic outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) eyes undergoing a treat and extend (TAE) regimen with faricimab, METHODS: Prospective interventional study on 33 eyes with treatment-naïve nAMD undergoing a loading phase of 4 monthly faricimab followed by a TAE regimen. Participants underwent functional assessment and retinal imaging with optical coherence tomography and angiography (OCT/OCTA), at baseline and follow-up visits (V0-V5). Primary outcomes were safety, changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST). Secondary outcomes included changes in OCT biomarkers (intraretinal and subretinal fluid [IRF and SRF], maximum pigment epithelium detachment [PED] height) and vascular densities (VD) in the superficial (SCP) and deep capillary plexuses (DCP).<br><br>RESULTS: Mean follow-up was 14.1&#x2009;&#xb1;&#x2009;2.7&#xa0;months. At the final visit, 36.4% eyes were on a q16w regimen, and 36.4% on q12w. Results showed significant reductions in CST (V0: 334&#x2009;&#xb1;&#x2009;102&#xa0;&#x3bc;m, V5: 227&#x2009;&#xb1;&#x2009;47&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.001), presence of IRF/SRF and PED height. BCVA improved significantly from 0.51&#x2009;&#xb1;&#x2009;0.23 to 0.36&#x2009;&#xb1;&#x2009;0.26 LogMAR (p&#x2009;=&#x2009;0.03). A dry macula after the loading phase was achieved in 63.7% of cases and correlated with longer inter-injections intervals during TAE. SCP's VD showed a transient decrease in V1-V3 but returned to baseline values at V5, while no significant changes were observed in DCP VD. No cases of intraocular inflammation or adverse events were observed.<br><br>CONCLUSION: Faricimab showed favorable results in treatment-naive nAMD, leading to structural and functional improvements and allowing for extended treatment intervals even in real-world setting.},
}
@article {pmid40327408,
year = {2025},
author = {Yi, W and Xu, M and Xue, Y and Cao, Y and Yang, Z and Zhou, L and Zhou, Y and Shi, L and Mai, X and Sun, Z and Qing, W and Li, Y and Qing, A and Zhang, K and Ou, L and Chen, S and Duh, EJ and Liu, X},
title = {A spontaneous nonhuman primate model of inherited retinal degeneration.},
journal = {JCI insight},
volume = {10},
number = {12},
pages = {},
pmid = {40327408},
issn = {2379-3708},
support = {R01 EY035549/EY/NEI NIH HHS/United States ; R01 EY035897/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Disease Models, Animal ; Macaca fascicularis ; *Bestrophins/genetics/metabolism ; *Retinal Degeneration/genetics/pathology ; Humans ; Male ; *Vitelliform Macular Dystrophy/genetics/pathology ; Female ; Retinal Pigment Epithelium/pathology ; Mutation ; Retinal Cone Photoreceptor Cells/pathology ; },
abstract = {Inherited retinal degenerations (IRDs) are important causes of progressive, irreversible blindness. Hereditary macular diseases, in particular, are significant in their effect on the specialized, central cone photoreceptor-rich macula responsible for high resolution vision. Autosomal dominant Best vitelliform macular dystrophy (BVMD), caused by variants in the BEST1 gene, is one of the most common inherited macular dystrophies. Gene therapies have emerged as promising treatments for IRDs, but a lack of suitable animal models has hindered progress both in treatments and in understanding the mechanisms underlying macular diseases. Here, we report a Macaca fascicularis carrying a heterozygous potential pathogenic BEST1p.Q327E variant that disrupts the BEST1 ion channel by destabilizing the A195 helix, mirroring the structural perturbations seen in certain human pathological mutants. Longitudinal imaging over 2 years revealed progressive macular changes, including subfoveal cleft enlargement, lipid-rich deposit accumulation, retinal pigment epithelium (RPE) disruption, and central-to-peripheral photoreceptor degeneration, recapitulating early human BVMD pathology. Histopathology demonstrated diminished BEST1 expression, attenuation of the RPE-photoreceptor interface, and 2 distinct types of lipid deposits, including heretofore unappreciated cone mitochondrial-enriched lesions, highlighting selective cone mitochondria vulnerability. This is, to our knowledge, the first nonhuman primate model of inherited macular dystrophy, and it links BEST1 mutations, mitochondrial dysfunction, and progressive macular degeneration, offering new insights into BVMD pathophysiology and highlighting its utility for studying disease progression and potential therapeutic interventions.},
}
@article {pmid40327010,
year = {2025},
author = {Thomsen, AK and Steffensen, MA and Nielsen, AT and Vorum, H and Honoré, B and Nissen, MH and Sørensen, TL},
title = {Chemokine System Changes Drive Age-Related Macular Degeneration and Influence Treatment Outcomes.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {5},
pages = {14},
pmid = {40327010},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Prospective Studies ; Aged ; *Chemokines/blood ; *Receptors, Chemokine/metabolism/blood ; Flow Cytometry ; Treatment Outcome ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Middle Aged ; *Wet Macular Degeneration/drug therapy/blood ; Monocytes/metabolism ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: The chemokine system is associated with age-related macular degeneration (AMD), shown in previous studies. In this study, we investigate these chemokines and chemokine receptors and their association with treatment response in neovascular AMD (nAMD), and association to intermediate AMD (iAMD).<br><br>METHODS: In this prospective cohort study, patients with nAMD, iAMD, and healthy controls were included. The initial and 1-year treatment response was evaluated in patients with nAMD. Plasma chemokine concentrations of CCL2, CCL3, CCL4, CCL20, CXCL8, and CXCL10 were measured with immunoassays. Chemokine receptor expression levels of CCR1, CCR2, CCR5, CCR6, CXCR2, CXCR3, and CX3CR1 on circulating T cells and monocytes were measured with flow cytometry. Correlation network analyses were performed of the chemokine system. Genotyping for CFH and ARMS2 risk polymorphisms was performed in patients with nAMD.<br><br>RESULTS: Patients with nAMD with poor initial treatment response had significantly lower proportions of CD4+CXCR3+, CCR5+ classical monocytes, and CCR2+ non-classical monocytes compared with good initial responders (all P < 0.05). Patients with nAMD with poor 1-year treatment response had significantly lower CD4+CXCR3+ and CCR2+ non-classical monocytes compared to good 1-year responders (both P < 0.05). Correlation networks revealed a more complex regulation in partial and poor initial treatment responders. Multiple chemokines and chemokine receptors significantly correlated with the risk genotypes of CFH and ARMS2.<br><br>CONCLUSIONS: Patients with nAMD with poor treatment response had dysregulation of the chemokine system. The chemokine system might be a potential target of novel treatment in nAMD. Further studies are needed to clarify the chemokine system's role in nAMD treatment response.},
}
@article {pmid40327005,
year = {2025},
author = {Chen, C and Lan, Y and Yan, W and Zhang, X and Li, T and Han, J},
title = {Exploring Therapeutic Targets for Age-Related Macular Degeneration From Circulating Proteins to Plasma Metabolites in the European Population.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {5},
pages = {8},
pmid = {40327005},
issn = {2164-2591},
mesh = {Humans ; *Macular Degeneration/genetics/blood ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Blood Proteins/metabolism ; Male ; Quantitative Trait Loci ; Aged ; Female ; Polymorphism, Single Nucleotide ; Europe ; White People/genetics ; White ; },
abstract = {PURPOSE: To explore the causal associations among circulating proteins, plasma metabolites, and age-related macular degeneration (AMD).<br><br>METHODS: We employed Mendelian randomization (MR) analysis and colocalization analysis to discern the causal relationship between proteomes and AMD. This investigation utilized data from protein quantitative trait loci (pQTL) studies in deCODE and the UK Biobank. Additionally, plasma metabolite-related genome-wide association studies (GWAS) data and AMD-related GWAS data were incorporated.<br><br>RESULTS: Our findings confirmed a potential causal relationship between cytoplasmic tryptophanyl-tRNA synthetase 1 (WARS1) and a higher risk of AMD. The observed causal impact of WARS1 on the two subtypes of AMD (dry and wet) align consistently with the aforementioned outcomes. Three plasma metabolites-N-acetyl-kynurenine, N-acetyltyrosine, and caproate (6:0)-were identified as mediators of the causal effect of WARS1 on AMD, and subgroup analysis revealed that N-acetyltyrosine is a specific negative metabolite associated with WARS1 and dry AMD, whereas X-16580 is a specific positive metabolite linked to WARS1 and wet AMD.<br><br>CONCLUSIONS: The outcomes of this study suggest a potential causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD by integrating multiple genetic analyses. Nevertheless, further research is essential to validate and strengthen these conclusions.<br><br>TRANSLATIONAL RELEVANCE: This study establishes the causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD.},
}
@article {pmid40326420,
year = {2025},
author = {Jaggi, D and Berger, LE and Zweifel, S and Becker, MD and Michels, S and Stalder, O and Lincke, JB and Habra, O and Wolf, S and Zinkernagel, MS},
title = {Comparison of treatment routine using aflibercept: Strict vs. relaxed retreatment regimen (TOLERANT study)-A non-inferiority, randomized controlled trial.},
journal = {Acta ophthalmologica},
volume = {103},
number = {6},
pages = {e385-e393},
pmid = {40326420},
issn = {1755-3768},
support = {//Bayer/ ; },
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Intravitreal Injections ; *Visual Acuity ; Female ; Male ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Retreatment ; Follow-Up Studies ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Fundus Oculi ; Middle Aged ; },
abstract = {PURPOSE: This trial evaluated the noninferiority of a relaxed compared to a strict treat-and-extend treatment strategy in patients with neovascular Age-related macular degeneration (AMD).<br><br>METHODS: Multicenter, randomized, controlled, phase IV, non-inferiority clinical trial. Patients with treatment-na&#xef;ve nAMD were randomized 1:1 to a relaxed or strict treat-and-extend treatment regimen. Aflibercept 2 mg/0.05 mL was used. In the relaxed regimen, up to 100 &#x3bc;m subfoveal subretinal fluid was tolerated, vs. no tolerance of any fluid in the strict regimen. The primary outcome was the change in best corrected visual acuity (BCVA; ETDRS letters) from baseline to the end of the study at week 104 and its difference between the two treatment arms, with a 5-letter non-inferiority margin.<br><br>RESULTS: We randomized 150 patients. The full analysis showed non-inferiority of the relaxed treatment, with a mean difference of -0.12 letters (95%-CI: -3.45 to infinity, H0; mean. diff. &#x2264;&#x2009;5 letters: p =&#x2009;0.008), and a visual acuity gain of 7.3 (4.82; 9.78) vs. 7.01 (3.67; 10.36) letters in the strict vs. relaxed regimen, respectively. Many patients deviated from the protocol due to Covid-19. Per-protocol analysis showed a mean difference of -1.78 letters (95%-CI: -6.61 to infinity, H0; mean. diff. &#x2264;&#x2009;5 letters: p =&#x2009;0.136). Fewer injections were needed in the relaxed regimen, with a mean difference of -2.34 (95%-CI: -4.11 to -0.56, p =&#x2009;0.01).<br><br>CONCLUSION: Tolerating up to 100 &#x3bc;m subfoveal subretinal fluid achieves good visual outcomes in our 24-month follow-up period, in patients treated with aflibercept for nAMD, with significantly fewer injections needed.},
}
@article {pmid40326035,
year = {2025},
author = {Guo, Y and Zhao, J and Chen, Z},
title = {Circulating Inflammatory Proteins and Age-related Macular Degeneration: New Insights from Mendelian Randomization.},
journal = {Combinatorial chemistry &amp; high throughput screening},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113862073373085250418113858},
pmid = {40326035},
issn = {1875-5402},
abstract = {BACKGROUND: Inflammation is a key mechanism underlying age-related macular degeneration (AMD); however, the specific circulating inflammatory proteins involved remain unclear. This study investigated the causal relationship between 91 circulating inflammatory proteins and AMD using a two-sample Mendelian randomization (MR) approach.<br><br>METHODS: We conducted a two-sample magnetic resonance imaging MR analysis using genomewide association study (GWAS) data. Five MR methodologies were applied, with inverse variance weighting (IVW) as the primary approach. We applied false discovery rate (FDR) correction to mitigate false positives. Sensitivity analyses were performed to assess horizontal pleiotropy and heterogeneity. Additionally, Steiger's test, reverse MR analysis, and linkage disequilibrium score regression (LDSC) were used to validate the results.<br><br>RESULTS: Five inflammatory proteins demonstrated significant associations with overall AMD, including three associated with wet AMD and one associated with dry AMD. LDSC analysis indicated that, except for fibroblast growth factor-19, no genetic correlation confounded the causal relationships. Additionally, the expression of the identified proteins was unaffected by the genetic prediction of AMD.<br><br>CONCLUSION: This study highlights the causal relationship between specific inflammatory proteins and AMD, emphasizing their potential roles in AMD pathogenesis and potential therapeutic targets.},
}
@article {pmid40324382,
year = {2025},
author = {Butovsky, O and Rosenzweig, N},
title = {Alzheimer's disease and age-related macular degeneration: Shared and distinct immune mechanisms.},
journal = {Immunity},
volume = {58},
number = {5},
pages = {1120-1139},
doi = {10.1016/j.immuni.2025.04.013},
pmid = {40324382},
issn = {1097-4180},
mesh = {Humans ; *Macular Degeneration/immunology/therapy ; *Alzheimer Disease/immunology/therapy ; Animals ; },
abstract = {Alzheimer's disease (AD) and age-related macular degeneration (AMD) represent the leading causes of dementia and vision impairment in the elderly, respectively. The retina is an extension of the brain, yet these two central nervous system (CNS) compartments are often studied separately. Despite affecting cognition vs. vision, AD and AMD share neuroinflammatory pathways. By comparing these diseases, we can identify converging immune mechanisms and potential cross-applicable therapies. Here, we review immune mechanisms highlighting the shared and distinct aspects of these two age-related neurodegenerative conditions, focusing on responses to hallmark disease manifestations, the opposite role of overlapping immune risk loci, and potential unified therapeutic approaches. We also discuss unique tissue requirements that may dictate different outcomes of conserved immune mechanisms and how we can reciprocally utilize lessons from AD therapeutics to AMD. Looking forward, we suggest promising directions for research, including the exploration of regenerative medicine, gene therapies, and innovative diagnostics.},
}
@article {pmid40324247,
year = {2025},
author = {Yang, Z and Cao, W and Qin, H and Lu, X and Wang, Y and Liu, D},
title = {Association between the weight-adjusted waist index and age-related macular degeneration: Results from NHANES 2005-2008.},
journal = {Medicine},
volume = {104},
number = {18},
pages = {e42348},
pmid = {40324247},
issn = {1536-5964},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Body Mass Index ; Cross-Sectional Studies ; *Macular Degeneration/epidemiology/etiology ; Nutrition Surveys ; *Obesity/epidemiology/complications ; Prevalence ; Risk Factors ; United States/epidemiology ; *Waist Circumference ; },
abstract = {The present study aimed to explore the association between weight-adjusted waist index (WWI) levels, a newly proposed indicator for assessing obesity, and the risk of age-related macular degeneration (AMD). A cross-sectional analysis of 20,497 participants was conducted using the National Health and Nutrition Examination Survey (NHANES) 2005-2008 dataset. Trend tests, multivariable logistic regression, and smoothing curve fitting were performed to examine the association between WWI and the risk of AMD. In addition, subgroup analysis and interaction tests were used to test this association in different groups. A total of 5476 participants were included in the study, of whom 420 (7.7%) had AMD. The risk of age-related macular degeneration increased with increasing WWI in all models. In the fully adjusted model, a 55% increase in the prevalence of AMD was observed in the highest tertile (tertile 3: >11.52) of WWI (OR 1.55, 95% CI 1.09, 2.21) compared to the lowest tertile (tertile 1: <10.85). The interaction tests revealed that age, chronic kidney disease, and cardiovascular disease had significant interactions with WWI on AMD risk (P for interaction < .05). This study revealed that higher WWI levels were associated with increased risk of AMD, suggesting that managing obesity according to WWI may reduce AMD risk. However, additional research is warranted to corroborate our results.},
}
@article {pmid40323558,
year = {2025},
author = {Reiter, GS and Borrelli, E and Dolz-Marco, R and Iezzi, R and Bakri, SJ},
title = {Imaging of Geographic Atrophy: A Practical Approach.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {7},
pages = {1621-1632},
pmid = {40323558},
issn = {2193-8245},
abstract = {Geographic atrophy (GA) secondary to age-related macular degeneration is a chronic degenerative disease involving the retinal pigment epithelium, photoreceptors, and choriocapillaris leading to irreversible loss of visual function. Identification of imaging markers associated with GA development and progression has progressed over the past decades, moving from two-dimensional to three-dimensional imaging, as well as image interpretation using artificial intelligence. However, there is an open discussion about the "must-haves" for GA detection and follow-up as well as complementary imaging. This practical approach provides an overview of the advantages of key imaging modalities for GA and their applicability in clinical and experimental settings.},
}
@article {pmid40323271,
year = {2025},
author = {Yoon, EG and Nam, KT and Choi, M and Choi, KE and Yun, C},
title = {Aqueous Humor Levels of Vascular Endothelial Growth Factor in Patients With Dry Age-Related Macular Degeneration and Subretinal Drusenoid Deposits.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {5},
pages = {10},
pmid = {40323271},
issn = {1552-5783},
mesh = {Humans ; *Aqueous Humor/metabolism ; Female ; Male ; *Retinal Drusen/metabolism/diagnosis ; *Vascular Endothelial Growth Factor A/metabolism ; Prospective Studies ; Aged ; Aged, 80 and over ; *Geographic Atrophy/metabolism/diagnosis ; Tomography, Optical Coherence ; Middle Aged ; Cytokines/metabolism ; Fluorescein Angiography ; },
abstract = {PURPOSE: We sought to investigate aqueous humor levels of growth factors and cytokines related to human angiogenesis in patients with dry age-related macular degeneration (AMD).<br><br>METHODS: This prospective study classified patients with dry AMD into two groups of patients-those with soft drusen and those with both soft drusen and subretinal drusenoid deposits (SDDs). Aqueous humor samples were collected from each group and from a control group to analyze intraocular cytokine concentrations and examine their associations with AMD characteristics.<br><br>RESULTS: A total of 48 participants, 16 per group, were enrolled in the study. The vascular endothelial growth factor (VEGF)-A level was highest in the soft drusen with SDD group (229.21 &#xb1; 88.26 pg/mL) compared to the soft drusen group (167.54 &#xb1; 92.71 pg/mL) and the control group (140.73 &#xb1; 84.91 pg/mL) (P = 0.021). There were no significant differences in the concentrations of angiopoietin-2, placental growth factor, interleukin-1&#x3b1;, interleukin-1&#x3b2;, interleukin-6, interleukin-10, or tumor necrosis factor-&#x3b1; among the groups (all P > 0.05). In the soft drusen with SDD group, a higher cube root of drusen volume (&#x3b2; = 0.533, P = 0.033) was significantly associated with an elevated VEGF-A level.<br><br>CONCLUSIONS: In eyes with dry AMD, those with both soft drusen and SDDs exhibited higher intraocular VEGF-A levels than those with only soft drusen, and these levels correlated with the cube root of drusen volume.},
}
@article {pmid40322902,
year = {2025},
author = {Kong, M and Lee, MY and Yang, W and Bae, JH and Kim, JM},
title = {Obesity, Nutritional Intake, and Age-Related Macular Degeneration: A Cross-Sectional Study Using Nationwide Survey Data from Korea.},
journal = {Ophthalmic epidemiology},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/09286586.2025.2500023},
pmid = {40322902},
issn = {1744-5086},
abstract = {Purpose: Dietary intake of nutrients seems to play a role in the prevention of age-related macular degeneration (AMD). It may be worthwhile to identify certain nutrients that are highly related to AMD when consumed in small amounts. This study aims to evaluate the association between nutritional intake and risk of AMD.Methods: A population-based cross-sectional study analyzed data from the Korean National Health and Nutrition Examination Survey (KNHANES) between 2010 and 2011, involving 6,471 participants aged 40 years or older. The presence and severity of AMD were graded using fundus photography. Multivariable regression analysis was employed to assess the association between dietary intake and AMD risk.Results: The prevalence of AMD among 6,471 participants was 8.9% (576 cases), comprising 8.2% (531) with early AMD and 0.7% (45) with late AMD. Multivariable-adjusted analyses revealed that, among obese individuals (body mass index ≥25), men with AMD had significantly lower intakes of fiber, ash, calcium, potassium, thiamin, and vitamin C compared to those without AMD (all p < 0.05). In obese women, AMD showed a significant association with lower intakes of protein, vitamin A, and carotene (all p < 0.05).Conclusions: An insufficient intake of certain nutrients was associated with an increased likelihood of AMD in obese individuals. Larger prospective cohort studies are needed to investigate the relationship between specific nutrients and the risk of AMD.},
}
@article {pmid40322303,
year = {2025},
author = {Cickusic, A and Pavljasevic, S and Jusufovic, V and Sefic-Kasumovic, S and Hasic, AP and Halilbasic, M},
title = {C-reactive Protein Levels in Prediction of the Development or the Progression of Agerelated Macular Degeneration in Patients Examined at Tuzla Canton.},
journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)},
volume = {79},
number = {1},
pages = {47-51},
pmid = {40322303},
issn = {1986-5961},
mesh = {Humans ; Female ; Male ; *C-Reactive Protein/analysis/metabolism ; Aged ; Middle Aged ; Disease Progression ; *Macular Degeneration/blood/diagnosis ; Case-Control Studies ; Retrospective Studies ; Prospective Studies ; Biomarkers/blood ; Bosnia and Herzegovina ; Inflammation/blood ; },
abstract = {BACKGROUND: Age-related macular degeneration (ARMD) is a chronic, incurable, progressive, multifactorial, neurodegenerative disease, which is one of the leading causes of visual impairment, among individuals above 60 years of age in developed countries. Over the past decades, the role of inflammation and CRP in the pathogenesis of ARMD has been investigated.<br><br>OBJECTIVE: The study aimed to investigate the association between inflammation or CRP levels in prediction the development or the progression of ARMD.<br><br>METHODS: This retrospective-prospective, case-control study, was conducted at the Clinic for Eye Diseases, University Clinical Center Tuzla, from 2020. to 2024. Two group of participants were included in this study. The first group (n=100 patients) consisted of patients diagnosed with different stages of ARMD, and second, control group (n=100 patients) consisted of patients without ARMD. The study included subjects of both sexes, divided into three age categories (&#x2264;55; 56-66; &#x2265;67 years). Detailed ocular and systemic evaluations were performed, including fundus examination and OCT angiography. A 5mL sample of venous blood was colected to determine serum CRP levels, for the both group of patients, using latex immunoassay method. Statistical analysis, including Student's t-test, Chi square test and posthoc (Turkey) tests, was conducted using SPSS 26 for Windows, with p<0,05 considered significant.<br><br>RESULTS: Out of 100 patients, 34 were having early, 18 intermediate and 48 were having advanced stages of ARMD. The mean serum CRP levels in the ARMD group (8.39&#xb1;27.22mg/L) were significantly higher compared to the control group, (2.52&#xb1;5.35mg/L), p=0,000. Also, serum CRP values by age category, between ARMD subjects and the control group, showed statistically significant differences in all age groups: &#x2264;55 p=0.032; 56-66 p=0.019; &#x2265;67 p=0.000. The mean serum CRP levels was 6.6&#xb1;6.9 mg/L, 10&#xb1;13.3 mg/L and 16&#xb1;22.7 mg/L, in early, intermediate and advanced ARMD, respectively. Comparing these CRP values and different stages of ARMD, there were found statistically significant differences between the three stages. Furthermore, these results showed that mean CRP values increase with disease severity.<br><br>CONCLUSION: Based on the obtained results serum CRP levels are significant risk factor in predicting the development and the progression of ARMD. Also, these results emphasize the role of systemic inflammation in the development and progression of ARMD.},
}
@article {pmid40321164,
year = {2025},
author = {Subhi, Y and Andersen, LMM and Hajari, JN and Henningsen, N and Larsen, KI and Schneider, M},
title = {Tailored Anti-VEGF Therapy with New Generation Optimizations (TANGO) Treatment Regimen for Neovascular Age-Related Macular Degeneration: Rationale, Design, and Simulation Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1435-1441},
pmid = {40321164},
issn = {1177-5467},
abstract = {PURPOSE: To present the rationale and design of the Tailored Anti-VEGF therapy with New Generation Optimizations (TANGO) treatment regimen for neovascular age-related macular degeneration and to simulate potential number of visits and injections with TANGO and compare to other treatment regimens.<br><br>METHODS: This is a descriptive short report of the rationale and design of TANGO. The purpose of TANGO is to lessen the burden of therapy with new generation anti-VEGF medications that have better durability. We also simulate the potential number of visits and injections during the first year with TANGO and compare these numbers to other treatment regimens.<br><br>RESULTS: Our report describes TANGO and provides a flow chart for its use. Our simulations suggest that TANGO may lead to a reduced number of visits and injections.<br><br>CONCLUSION: Our simulations suggest that employing TANGO may lead to a reduced number of visits and anti-VEGF injections while still providing intensive therapy for those who require it. However, it should be emphasized that this is a descriptive report and a simulation study, and clinical real-world studies of efficacy and safety using TANGO are warranted to better understand implications of employing TANGO in routine clinical practice.},
}
@article {pmid40320376,
year = {2025},
author = {Niyazmand, N and Alam, K and Wood, H and Charng, J and Gerritsma, S and Niyazmand, H},
title = {Eye health literacy across the world and in Australia.},
journal = {Clinical &amp; experimental optometry},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/08164622.2025.2492768},
pmid = {40320376},
issn = {1444-0938},
abstract = {Eye health literacy is an important factor in determining eye health outcomes. Ophthalmic disorders are increasingly common due to various factors associated with ageing population and other important determinants of health such as socio-economic status, environmental, cultural, individual, behavioural, and biological factors. Therefore, understanding the importance of health literacy in promoting preventive practices, early identification, and prompt management of eye diseases is critical. Currently, glaucoma, diabetic retinopathy, and age-related macular degeneration are the leading causes of irreversible vision impairment. However, the impact of enhanced eye health literacy on these diseases has not been sufficiently studied. In this topical review, findings from relevant peer-reviewed articles published after 1998 are presented. The results indicate that enhancing knowledge about eye health and ophthalmic care can significantly contribute to the prevention and management of these conditions, and thus decrease the burden of vision impairment. Patients with adequate health literacy can make informed decisions about their health, adhere to treatment programs, and communicate effectively with healthcare providers. Educational level, socioeconomic status, age, gender, family history of eye disease, regular eye check-ups, and remoteness influence the level of health literacy across the world. However, due to differences in health infrastructure, geographical and cultural characteristics, research conducted in other countries is not necessarily applicable in Australia. In summary, despite the increasing burden of vision impairment, there is a lack of wholistic research regarding the status of eye health literacy in Australia and abroad, therefore suggesting a critical gap in research and universal eye health literacy tools.},
}
@article {pmid40320193,
year = {2025},
author = {Campochiaro, PA},
title = {Sustained Suppression of VEGF for Treatment of Retinal and Choroidal Vascular Diseases.},
journal = {American journal of ophthalmology},
volume = {277},
number = {},
pages = {1-6},
doi = {10.1016/j.ajo.2025.04.032},
pmid = {40320193},
issn = {1879-1891},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Retinal Diseases/drug therapy ; Wet Macular Degeneration/drug therapy ; *Choroid Diseases/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Choroidal Neovascularization/drug therapy ; },
abstract = {Clinical trials have demonstrated remarkable benefits from intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents in patients with retinal or choroidal vascular diseases, but observational studies have shown poor outcomes in the same patient populations treated in clinical practice, and this is associated with less frequent injections. Current treatment strategies in clinical practice are designed to minimize injection frequency, which involves imprecise estimates of when recurrent exudation might occur. An alternative strategy is to use treatments that provide sustained suppression of VEGF, but many retina specialists are concerned that such treatments may damage the macula and cause atrophy, particularly in patients with neovascular age-related macular degeneration (nAMD). Evidence regarding the potential benefits and risks of sustained suppression of VEGF is provided along with an overview of treatments aimed at achieving it, one that is currently available to treat patients with nAMD and diabetic macular edema and others that are in development. The overview of these various treatment strategies is an introduction to other articles in this special issue that provide detailed background and currently available data. We are entering a new era in the treatment of retinal and choroidal vascular diseases and this issue is designed to provide a guidebook of what is here and what is about to come.},
}
@article {pmid40320035,
year = {2025},
author = {Ashrafkhorasani, M and Abbasgholizadeh, R and Habibi, A and Emamverdi, M and Nittala, MG and Aghayee, MM and Wykoff, CC and Sadda, SR},
title = {Quantitative comparison of inner and outer retinal intraretinal hyperreflective foci in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {256},
number = {},
pages = {110415},
doi = {10.1016/j.exer.2025.110415},
pmid = {40320035},
issn = {1096-0007},
mesh = {Humans ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Aged ; Male ; Aged, 80 and over ; Fluorescein Angiography/methods ; Visual Acuity/physiology ; *Macular Degeneration/diagnosis ; *Wet Macular Degeneration/diagnosis/physiopathology ; Middle Aged ; },
abstract = {To quantitatively compare the spectral-domain optical coherence tomography (SD-OCT) characteristics of inner and outer intraretinal hyperreflective foci (IHRF) in eyes with age-related macular degeneration (AMD) and to investigate their potential pathophysiological implications. This retrospective study included 64 eyes from 64 treatment-naive AMD patients. SD-OCT imaging (Spectralis, Heidelberg Engineering) was performed using a 20° × 20° macular scan centered on the fovea. Inner IHRF were defined as lesions located above the inner border of the inner nuclear layer, while outer IHRF were situated below the inner border of outer nuclear layer. Semi-automated segmentation and quantitative analysis of IHRF were performed using ImageJ. Parameters analyzed included mean area, normalized mean reflectivity, greatest linear dimension (GLD), and mean circularity. A total of 32 eyes with 68 inner IHRF and 32 eyes with 113 outer IHRF were included. The mean area of inner and outer IHRF was 887.09 ± 942.63 μm[2] and 832.27 ± 881.75 μm[2], respectively (p = 0.69). Normalized reflectivity was 1.18 ± 0.14 for inner IHRF versus 1.20 ± 0.17 for outer IHRF (p = 0.54), and circularity was 0.81 ± 0.19 for inner IHRF versus 0.79 ± 0.20 for outer IHRF (p = 0.71). The mean GLD measured 42.8 ± 35.2 μm for inner IHRF and 45.3 ± 30.4 μm for outer IHRF (mean difference: 2.5 μm, 95 % CI: 7.57 to 12.57; p = 0.595). No statistically significant differences were observed between inner and outer IHRF in any evaluated parameters. Inner and outer IHRF in AMD share similar quantitative SD-OCT characteristics, suggesting common pathological mechanisms irrespective of retinal location. These findings challenge the notion of distinct cellular origins and highlight the need for further research.},
}
@article {pmid40319468,
year = {2025},
author = {Rowe, LW and Akotoye, C and Harris, A and Ciulla, TA},
title = {Beyond the injection: delivery systems reshaping retinal disease management.},
journal = {Expert opinion on pharmacotherapy},
volume = {26},
number = {8},
pages = {939-952},
pmid = {40319468},
issn = {1744-7666},
support = {R01 EY030851/EY/NEI NIH HHS/United States ; R01 EY034718/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Drug Delivery Systems ; *Retinal Diseases/drug therapy/physiopathology ; Intravitreal Injections ; Animals ; Diabetic Retinopathy/drug therapy ; },
abstract = {INTRODUCTION: Intravitreal injections remain the standard for treating common retinal diseases including age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy. However, frequent administration creates significant treatment burden due to limited drug half-life and the chronic nature of these conditions.<br><br>AREAS COVERED: This review summarizes emerging drug delivery techniques and therapies for retinal disease that have achieved FDA approval within the past five years or have advanced to Phase 3 development, including intravitreal sustained-release platforms and alternative delivery routes (suprachoroidal, subretinal, topical, and subcutaneous). Specific innovations discussed include the ranibizumab port delivery system, EYP-1901 (Duravyu, vorolanib implant), KSI-301 (tarcocimab tedromer), KSI-501, OTX-TKI (Axpaxli, axitinib implant), 4D-150, revakinagene taroretcel-lwey (Encelto, NT-501, encapsulated cell therapy), Xipere (triamcinolone acetonide injectable suspension), AU-011 (belzupacap sarotalocan targeted delivery), ABBV-RGX-314, elamipretide, and OCS-01 (high concentration dexamethasone).<br><br>EXPERT OPINION: Promising innovations include sustained-release intravitreal implants, topical and subcutaneous delivery systems, and targeted methods like suprachoroidal and subretinal injections, each with unique advantages and limitations. Challenges include overcoming the blood-retinal barrier, surgical complications with implantable devices, and ensuring patient adherence. Advances in smart delivery systems, drug formulations, and predictive models, alongside interdisciplinary collaboration, will be crucial in achieving personalized, effective, and sustainable retinal therapies.},
}
@article {pmid40319200,
year = {2025},
author = {Vandebroek, AC and Rickmann, A and Boden, KT and Seitz, B and Szurman, P and Schulz, A},
title = {Thrombolytic activity of recombinant tissue-type plasminogen activator (rtPA) in in-vitro model for subretinal hemorrhages.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {164},
pmid = {40319200},
issn = {1573-2630},
mesh = {Humans ; *Tissue Plasminogen Activator/therapeutic use/pharmacology ; *Thrombolytic Therapy/methods ; *Fibrinolytic Agents/therapeutic use/pharmacology ; *Retinal Hemorrhage/drug therapy ; Recombinant Proteins/pharmacology ; Male ; In Vitro Techniques ; Female ; Adult ; },
abstract = {PURPOSE: Recombinant tissue-type plasminogen activator (rtPA) has become central to the treatment of subretinal hemorrhages. However, individual results show highly variable and unpredictable efficacy of thrombolytic function. The aim of this study is to investigate the thrombolytic activity of rtPA in an in-vitro model for submacular hemorrhages.<br><br>METHODS: Using UV/Vis spectroscopy, the thrombolytic activity of rtPA was analyzed in an in-vitro model for subretinal hemorrhages with citrated human venous blood from 24 volunteers. The effects of blood clot volume (20 &#xb5;L and 100 &#xb5;L) and age (1d and 4d), rtPA concentration (0, 10, 50, 100, 150, and 200&#xa0;&#xb5;g/mL), and incubation time (30&#xa0;min, 1d, and 2d) on thrombolysis was analyzed on blood clots prepared through different synthesis routes (tube vs. hanging droplet).<br><br>RESULTS: For each period of incubation with rtPA, thrombolysis was significantly reduced for large blood clots with a volume of 100 &#x3bc;L compared with 20 &#x3bc;L blood clots. We found significantly more thrombolysis in 4-day-old clots than in 1-day-old clots after 30&#xa0;min incubation with rtPA for each blood clot size studied. For each blood clot size and age as well as rtPA incubation time, thrombolysis did not increase linearly across the tested concentrations. Thrombolysis was significantly lower after 30&#xa0;min than after 1d and 2d rtPA incubations.<br><br>CONCLUSION: The effectiveness of thrombolysis with rtPA increases with smaller clot size (20 &#xb5;L), increasing clot age (4d), and increasing incubation time (1-2d). Within the range of biocompatible rtPA concentrations, there was no concentration effect of rtPA on thrombolysis.},
}
@article {pmid40319174,
year = {2025},
author = {Avadzadeh, S and Sharma, A and Parvaresh, MM and Ghasemi Falavarjani, K and , },
title = {Aflibercept 2 mg biosimilar (Tyalia)-real-world experience from IRAN (ATRIA study).},
journal = {Eye (London, England)},
volume = {39},
number = {11},
pages = {2159-2163},
pmid = {40319174},
issn = {1476-5454},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use/antagonists &amp; inhibitors ; Retrospective Studies ; Male ; Female ; Aged ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Visual Acuity/physiology ; *Biosimilar Pharmaceuticals/administration &amp; dosage/therapeutic use/adverse effects ; *Macular Edema/drug therapy/physiopathology/diagnosis ; Middle Aged ; *Retinal Vein Occlusion/drug therapy/physiopathology/diagnosis ; Iran ; Diabetic Retinopathy/drug therapy/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Treatment Outcome ; Tomography, Optical Coherence ; Aged, 80 and over ; },
abstract = {PURPOSE: To evaluate the early real-world clinical outcomes regarding safety and efficacy after administering the aflibercept 2 mg biosimilar (Tyalia, Cinnagen, Tehran, Iran).<br><br>METHODS: A retrospective, uncontrolled observational study was conducted with a total of 499 Tyalia injections given in 189 eyes of 148 patients for variable indications. All patients were treated with at least one intravitreal injection of Tyalia 2&#x2009;mg; 102 eyes with neovascular age-related macular degeneration (n-AMD), 67 eyes with diabetic macular oedema (DMO), and 20 eyes with retinal vein occlusion (RVO) associated with macular oedema were included in the analysis.<br><br>RESULTS: The mean central subfield thickness (CST) of the overall group improved from baseline to the last follow-up from 408.8&#x2009;&#xb1;&#x2009;155.1&#x2009;&#xb5; to 353.4&#x2009;&#xb1;&#x2009;142.4&#x2009;&#xb5; (p&#x2009;<&#x2009;0.001). Best corrected visual acuity was found to be stable in the total cohort. The total number of adverse events (AEs) was (0.4%).<br><br>CONCLUSIONS: The preliminary real-world data from this limited early series suggest that Tyalia appears to have similar clinical efficacy and safety as aflibercept 2&#x2009;mg innovator across the approved indications. However, long-term data with a larger population are needed to further strengthen the findings of this study.},
}
@article {pmid40319159,
year = {2025},
author = {Yoon, JM and Noh, H and Nam, SW and Ham, DI},
title = {Peripheral retinal and choroidal thickness of eyes with reticular pseudodrusen.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {8},
pages = {2209-2218},
pmid = {40319159},
issn = {1435-702X},
mesh = {Humans ; *Choroid/pathology ; *Tomography, Optical Coherence/methods ; Aged ; Female ; Male ; *Retinal Drusen/diagnosis ; *Retina/pathology ; Fluorescein Angiography/methods ; Fundus Oculi ; Retrospective Studies ; Aged, 80 and over ; Visual Acuity ; Follow-Up Studies ; Middle Aged ; },
abstract = {PURPOSE: This study aimed to investigate the peripheral retinal and choroidal thicknesses in eyes with reticular pseudodrusen (RPD).<br><br>METHODS: Imaging data of ultrawide-field swept-source optical coherence tomography taken from 40 patients with age-related macular degeneration (AMD) were analyzed. Thirty-nine eyes of 20 patients had RPD (RPD group) and 39 eyes of 20 patients had no RPD (control group). Eyes with RPD were divided into localized/intermediate and diffuse types according to the fundus distribution. The retinal and choroidal thicknesses were measured at the fovea and six peripheral points in each eye, and the results were statistically analyzed.<br><br>RESULTS: The mean ages were 78.0&#x2009;&#xb1;&#x2009;6.1&#xa0;years in the RPD group and 74.4&#x2009;&#xb1;&#x2009;7.2&#xa0;years in the control group. The RPD group showed a thinner retina only at the nasal point (p&#x2009;=&#x2009;0.002) than the control group. The choroid was significantly thinner in the RPD group than in the control group at most peripheral points, except for the far temporal and far inferior points. Diffuse and localized/intermediate types of RPD eyes showed no significant difference in choroidal thickness, except at the nasal point, which was thinner in the diffuse type (p&#x2009;=&#x2009;0.049).<br><br>CONCLUSION: In eyes with RPD, most peripheral retinal thicknesses were not different from those of eyes with AMD without RPD; however, most peripheral choroidal thicknesses were thinner regardless of the fundus distribution status of the RPD. Nasal choroidal thickness may be associated with RPD severity.},
}
@article {pmid40318376,
year = {2025},
author = {Di Meo, C and Tisi, A and Lizzi, AR and Palaniappan, S and Pulcini, F and Cinque, B and Delle Monache, S and Nazarè, M and Hsu, E and Rapino, C and Maccarrone, M},
title = {Development of a human RPE In vitro model with AMD-like features reveals blue light-induced modulation of the endocannabinoid system.},
journal = {Biochemical and biophysical research communications},
volume = {767},
number = {},
pages = {151896},
doi = {10.1016/j.bbrc.2025.151896},
pmid = {40318376},
issn = {1090-2104},
mesh = {Humans ; *Retinal Pigment Epithelium/radiation effects/pathology/metabolism ; *Macular Degeneration/pathology/metabolism/etiology ; *Light/adverse effects ; *Endocannabinoids/metabolism ; Oxidative Stress/radiation effects ; Cellular Senescence/radiation effects ; *Models, Biological ; Receptor, Cannabinoid, CB1/metabolism/genetics ; Receptor, Cannabinoid, CB2/metabolism/genetics ; Blue Light ; },
abstract = {Blue light (BL) is a known risk factor for age-related macular degeneration (AMD), a retinal pathology where damage to the retinal pigment epithelium (RPE) is one of the earliest events. While the endocannabinoid system (ECS) is implicated in various physio-pathological conditions of the retina, its role in BL-injured RPE has not yet been addressed. To fill this gap, we developed an in vitro model of BL-induced human RPE damage showing key features of AMD: cytotoxicity, cell cycle arrest, oxidative stress, inflammation, and cellular senescence. Notably, our model demonstrates modulation of gene and protein expression of specific ECS elements, particularly cannabinoid receptors 1 and 2 (CB1 and CB2), thus providing unprecedented evidence of ECS dysregulation in RPE cells upon BL exposure.},
}
@article {pmid40317724,
year = {2025},
author = {Dalvi, S and Singh, R},
title = {Protocol for immunofluorescence characterization of drusen in induced pluripotent stem cell-derived retinal pigment epithelium cultures.},
journal = {STAR protocols},
volume = {6},
number = {2},
pages = {103791},
pmid = {40317724},
issn = {2666-1667},
support = {R01 EY028167/EY/NEI NIH HHS/United States ; R01 EY030183/EY/NEI NIH HHS/United States ; R01 EY033192/EY/NEI NIH HHS/United States ; R21 EY030817/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/cytology/metabolism/pathology ; *Induced Pluripotent Stem Cells/cytology/metabolism ; Humans ; *Retinal Drusen/pathology/metabolism ; *Fluorescent Antibody Technique/methods ; *Cell Culture Techniques/methods ; Cells, Cultured ; Microscopy, Confocal/methods ; Macular Degeneration/pathology ; },
abstract = {Drusen, lipoprotein-rich deposits underlying retinal pigment epithelium (RPE), are a pathological hallmark of age-related macular degeneration and related macular dystrophies. Here, we describe a protocol for visualizing drusen deposits beneath induced pluripotent stem cell (iPSC)-RPE (iRPE) monocultures. We describe steps for iRPE cell culture and, subsequently, enzymatic removal of the iRPE monolayer and immunostaining of sub-RPE drusen deposits. We then detail steps for confocal microscopy imaging of immunostained drusen in iRPE culture. For complete details on the use and execution of this protocol, please refer to Dalvi et al.[1].},
}
@article {pmid40317363,
year = {2025},
author = {Electra, J and Theodoraliu, E and Lazarus, G and Lestari, YD and Djatikusumo, A},
title = {The effect of caffeine consumption on age-related macular degeneration: a systematic review and meta-analysis.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {158},
pmid = {40317363},
issn = {1573-2630},
mesh = {Humans ; *Caffeine/administration &amp; dosage ; Disease Progression ; *Macular Degeneration/diagnosis/prevention &amp; control ; },
abstract = {PURPOSE: To explore the state-of-the-art evidence on the effect of caffeine consumption on the development and progression of age-related macular degeneration (AMD), a significant cause of blindness worldwide.<br><br>METHODS: Eligible primary clinical studies published up to 15 June 2024 were included and appraised using the Joanna Briggs Institute critical appraisal tools for cohort and case-control studies. The available data were then analyzed using random-effects meta-analysis and effect direction-based vote-counting (PROSPERO CRD42023451237).<br><br>RESULTS: Five studies (9318 patients) were included in this systematic review, three of which investigated the effect of caffeine intake on the development of AMD and two on AMD progression. Caffeine intake from coffee or other beverages showed no significant association with the occurrence of early (adjusted odds ratio 1.11 [95% confidence interval 0.93-1.33], I[2]&#x2009;=&#x2009;0.0%) or late AMD. On the other hand, vote-counting analysis indicated that caffeine consumption, mainly tea, may prevent and hinder disease progression, potentially in a dose-dependent manner.<br><br>CONCLUSION: The limited available evidence suggests that caffeine consumption may deter and impede the progression of AMD. In contrast, the protective effect of caffeine consumption on the development of AMD remains uncertain. Further prospective, large-scale studies exploring the effects and dose-response relationship of various caffeine beverages across a broader spectrum of AMD and populations are warranted to corroborate our findings.},
}
@article {pmid40316047,
year = {2025},
author = {Sirks, MJ and van Dijk, EHC and Ghalayini, H and Bazdar, S and Yu, W and Yzer, S and Martinez Ciriano, JP and Schlingemann, RO and Diederen, RMH and Boon, CJF},
title = {The Clinical Spectrum of Polypoidal Choroidal Vasculopathy in White Patients: A Retrospective Multicenter Cohort Study.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {10},
pages = {994-1004},
doi = {10.1016/j.oret.2025.04.019},
pmid = {40316047},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Choroid/blood supply/diagnostic imaging ; *Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Netherlands/epidemiology ; *Polypoidal Choroidal Vasculopathy/diagnosis/epidemiology/ethnology ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; *Visual Acuity ; White People/statistics &amp; numerical data ; },
abstract = {PURPOSE: To describe clinical characteristics of polypoidal choroidal vasculopathy (PCV) in a large White cohort.<br><br>DESIGN: Multicenter retrospective cohort study in 3 tertiary referral centers in the Netherlands.<br><br>SUBJECTS: White patients with an indocyanine green angiography-confirmed diagnosis of PCV in 1 or both eyes.<br><br>METHODS: The medical charts and multimodal imaging (MMI) of the included patients were assessed retrospectively by 2 independent assessors. Any discrepancies between graders were resolved by a senior retinal specialist. A predefined set of phenotypic characteristics was graded on MMI, including OCT, color fundus photography, fundus fluorescein angiography, and indocyanine green angiography.<br><br>MAIN OUTCOME MEASURES: Patients with polypoidal choroidal vasculopathy were distributed among 4 phenotypically different types, based on a previously published description: PCV with drusenoid age-related macular degeneration (AMD): PCV-AMD (type A); PCV without drusen but with a branching neovascular network (BNN): PCV-BNN (type B); isolated polypoidal choroidal vasculopathy (PCV-i) without drusen or a BNN: PCV-i (type C); and PCV with a background of central serous chorioretinopathy (CSC): PCV-CSC (type D).<br><br>RESULTS: We included 332 eyes of 305 patients with PCV, with 179 of 305 patients being female (58.7%). The average age at diagnosis was 73 years. The included eyes had the following types: PCV-AMD in 188 eyes (58.4%); PCV-BNN in 61 eyes (18.9%); PCV-i in 15 eyes (4.7%); and PCV-CSC in 58 eyes (18.0%). Patients with PCV-AMD were older and more often female than patients with PCV-CSC. The median best-corrected visual acuity of affected eyes was 0.30 logarithm of the minimum angle of resolution (interquartile range, 0.10-0.52), with a large range in each type. A median of 2 polypoidal lesions per eye was found (range, 1-12), with no significant differences between types. The choroidal thickness beneath the fovea and beneath polypoidal lesions was significantly higher in PCV-CSC than in PCV-AMD (both P < 0.001).<br><br>CONCLUSIONS: Polypoidal choroidal vasculopathy in White patients comprises a spectrum of different phenotypes: it may present with signs of drusenoid AMD, with a background of CSC, or without signs of either diseases. We found a different phenotype distribution when compared with published findings in Asian patients with PCV.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid40314640,
year = {2025},
author = {Muth, DR and Quérat, L and Venkataraman, AP and Dominguez-Vicent, A and Petrovski, G and Williams, PA and Locri, F and Zweifel, SA and Kvanta, A},
title = {Long-Term Natural History of Treatment-Naïve Geographic Atrophy in Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {5},
pages = {5},
pmid = {40314640},
issn = {2164-2591},
mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnostic imaging/pathology ; Male ; Female ; Aged ; Prospective Studies ; *Macular Degeneration/complications ; Aged, 80 and over ; Middle Aged ; Tomography, Optical Coherence/methods ; Visual Acuity ; Fluorescein Angiography/methods ; Disease Progression ; Follow-Up Studies ; Fundus Oculi ; },
abstract = {PURPOSE: To evaluate the long-term fundus autofluorescence-based growth rate (GR) of treatment-naïve patients with geographic atrophy (GA) in age-related macular degeneration.<br><br>METHODS: We conducted a prospective, single-center, observational study between February 2013 and September 2024 at the Department of Clinical Neuroscience, Karolinska Institutet, and St. Erik Eye Hospital, Stockholm/Solna, Sweden. Clinical examination and fundus autofluorescence were performed in patients with GA owing to dry age-related macular degeneration. The area and the absolute and square root transformed GR were analyzed every 6 months.<br><br>RESULTS: We examined 432 eyes and enrolled 204 eyes (111patients). The median follow-up was 21 months (minimum-maximum, 5-123). Of 73 fovea-sparing, 22 eyes converted to foveal-involving over a median of 24 months. The mean growth for the total cohort was 1.597 mm2/y and 0.264 mm/y after square root transformation. Bilateral (1.621 mm2/y; 0.267 mm/y), multifocal (1.961 mm2/y; 0.322 mm/y), and fovea-sparing (1.987 mm2/y; 0.234 mm/y) lesions showed significantly faster growth when analyzed in isolation. In a mixed statistical model that controlled for bilaterality, only fovea status remained a significant influencer on the square root transformed GR (P < 0.001).<br><br>CONCLUSIONS: In this long-term GA cohort, an influence of lesion characteristics on GRs can be observed. Fovea sparing, multifocality, and bilaterality showed faster growth, depending on the statistical model. Patients presenting with one or more of these lesion characteristics hold a high potential for benefit of future treatments because a growth slow down may be more likely to be achieved. In fovea-sparing cases, functional preservation may be possible.<br><br>TRANSLATIONAL RELEVANCE: By analyzing the data of one of the most extensive geographic atrophy patient cohorts in the Nordics, this study establishes a dataset on the long-term treatment-na&#xef;ve growth dynamics. It provides a reference for upcoming preclinical treatment developments and clinical trial end points.},
}
@article {pmid40313404,
year = {2025},
author = {Ceruso, FM and Leon, SGZ and Fiorillo, L and Cervino, G and Cicciù, M and Heboyan, A and Pernice, F and Meloni, S and Tallarico, M},
title = {Periodontal Disease and Age-Related Maculopathy: A Case Report.},
journal = {Clinical medicine insights. Case reports},
volume = {18},
number = {},
pages = {11795476251333251},
pmid = {40313404},
issn = {1179-5476},
abstract = {Age-related macular degeneration (AMD) is a leading cause of significant vision impairment in individuals aged 50 and older, primarily impacting central vision. This study seeks to investigate potential associations between periodontal disease and age-related maculopathy in the analyzed clinical case. A male subject of 66 years old, with age-related degenerative maculopathy and severe periodontal disease, was evaluated and treated. After an initial phase of non-surgical causal periodontal therapy, the periodontal indices were re-evaluated. In addition, the extraction of hopeless teeth replaced by dental implants was performed. A retinal topography was used to assess possible regression of the pathology, and proper anti-VEGF therapy was administered. The results showed a regression of periodontal disease and an improvement of the degenerative maculopathy. These preliminary results, even if encouraging, should be supported by larger prospective trials.},
}
@article {pmid40313258,
year = {2025},
author = {Sampson, J and Segrè, AV and Bujakowska, KM and Haynes, S and Baralle, D and Banka, S and Black, GC and Sergouniotis, PI and Ellingford, JM},
title = {Paired DNA and RNA sequencing uncovers common and rare genetic variants regulating gene expression in the human retina.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {40313258},
support = {/WT_/Wellcome Trust/United Kingdom ; R01 EY031424/EY/NEI NIH HHS/United States ; R01 EY035717/EY/NEI NIH HHS/United States ; },
abstract = {Genetic disorders impacting vision affect millions of individuals worldwide, including age-related macular degeneration (common) and inherited retinal disorders (rare). There is incomplete understanding of the impact of genetic variation on gene expression in the human retina, and its role in genetic disorders. Through the generation of whole genome sequencing and bulk RNA-sequencing of neurosensory retina (NSR) and retinal pigment epithelium (RPE) from 201 post-mortem eyes, we uncovered common and rare genetic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci (eQTLs) impacting 9,959 and 3,699 genes in NSR and RPE, respectively, with associated genetic variants enriched to cis-candidate regulatory elements and notable shared eGenes between NSR and RPE. We also detected 1051 expression outliers and prioritised 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.},
}
@article {pmid40312829,
year = {2025},
author = {Thier, A and Wolfram, C and Witt, U and Zeitz, O and Himmelsbach, I and Holmberg, C},
title = {Understanding access challenges to low vision care for age-related macular degeneration in Germany: results from an integrated synthesis based on experiences from affected individuals and care providers.},
journal = {Disability and rehabilitation},
volume = {47},
number = {23},
pages = {6033-6048},
doi = {10.1080/09638288.2025.2493213},
pmid = {40312829},
issn = {1464-5165},
mesh = {Humans ; *Health Services Accessibility ; *Macular Degeneration/rehabilitation/complications ; Germany ; *Vision, Low/rehabilitation/etiology ; Female ; Male ; Aged ; Interviews as Topic ; Qualitative Research ; Middle Aged ; Ophthalmologists ; },
abstract = {PURPOSE: To understand the reasons for the inconsistent and often arbitrary access to low vision care for people with age-related macular degeneration (AMD), this article examines the challenges of access to low vision care from the perspectives of people with AMD, ophthalmologists, opticians and low vision professionals.<br><br>METHODS: This article is based on a mixed-methods study that incorporated narrative semi-structured interviews to explore the experiences of individuals diagnosed with AMD, as well as online surveys to evaluate ophthalmologists' and opticians' knowledge of low vision services and expert discussions with low vision professionals. An integrated synthesis approach was employed.<br><br>RESULTS: Challenges in accessing low vision care can be categorized into four levels: individual, social, infrastructural, and provider. Individual challenges included information needs, perceptions of support services as stigmatizing or unhelpful, and immobility of the affected individuals. Social networks play a crucial role in supporting or hindering access to care. Limited service availability poses a significant infrastructural challenge. Provider-level issues include communication barriers, knowledge gaps, and insufficient collaboration among low vision providers.<br><br>CONCLUSIONS: Our study emphasizes the need for a structured, interdisciplinary rehabilitation approach to improve care for individuals with AMD.},
}
@article {pmid40312645,
year = {2025},
author = {Siedlecki, J and Priglinger, SG},
title = {[Age-related macular degeneration: Current treatment options and innovative research approaches].},
journal = {MMW Fortschritte der Medizin},
volume = {167},
number = {8},
pages = {51-53},
doi = {10.1007/s15006-025-4811-0},
pmid = {40312645},
issn = {1613-3560},
}
@article {pmid40312555,
year = {2025},
author = {Li, DL and Liu, JH and Dong, XX and Lanca, C and Grzybowski, A and Zhang, LJ and Pan, CW},
title = {Non-inferiority trials in clinical ophthalmology: a systematic review.},
journal = {Eye (London, England)},
volume = {39},
number = {11},
pages = {2151-2158},
pmid = {40312555},
issn = {1476-5454},
mesh = {Humans ; *Ophthalmology/methods ; *Equivalence Trials as Topic ; *Eye Diseases/therapy ; *Randomized Controlled Trials as Topic/methods ; },
abstract = {PURPOSE: To summarize the characteristics and methodology of non-inferiority trials in ophthalmology, aiding researchers in understanding the applications and limitations of such trials in ophthalmic diseases.<br><br>METHODS: PubMed, Web of Science, Embase and Scopus were searched for literature on non-inferiority randomized trials in ophthalmology published between 2000 and November 5 2023. Data on the basic characteristics were extracted and summarized. The Risk of Bias 2's was used to assess the bias risk.<br><br>RESULTS: A total of 294 papers were included, with 77.6% of the trials conducted in the last 10 years, and more than 2/3 (72.1%) were multicenter studies, and 79.9% were registered on platforms. The majority of trials were applied in the researches of glaucoma, cataract, age macular degeneration, macular edema, dry eye, myopia, or refractive error. Non-inferiority thresholds were reported in 88.4% of the trials. Intent-to-treat analysis was the primary outcome analysis method in only 21.8% of trials, while both intent-to-treat and per-protocol analyses were used in 29.6%. Last observation carried forward method was used to address missing values in 23.5%. However, 56.5% of the articles did not report how missing values were handled, leaving uncertainty regarding whether missing data was considered in the analysis. About 20.7% of the studies were at high risk of bias, mainly due to outcome measures and missing value treatments.<br><br>CONCLUSION: Non-inferiority trials are commonly used in ophthalmologic research to assess the effectiveness, safety, cost-effectiveness of treatments or surgical methods, but the quality of implementation and reporting needs to be improved.},
}
@article {pmid40311699,
year = {2025},
author = {Lee, CS and Su, YR and Walker, RL and Krakauer, C and Blazes, M and Johnson, EA and Cronkite, D and Bowers, W and Hess, C and Arterburn, D and Agrón, E and Chew, EY and Crane, PK},
title = {A Data-driven Age-related Macular Degeneration Severity Scoring System Leveraging the AREDS Studies and Clinical Electronic Medical Records.},
journal = {Ophthalmology},
volume = {132},
number = {10},
pages = {1076-1087},
pmid = {40311699},
issn = {1549-4713},
support = {OT2 OD032644/OD/NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; U01 AG006781/AG/NIA NIH HHS/United States ; U19 AG066567/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; *Electronic Health Records/statistics &amp; numerical data ; *Geographic Atrophy/diagnosis/drug therapy/classification ; Intravitreal Injections ; Natural Language Processing ; Retrospective Studies ; Severity of Illness Index ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; *Wet Macular Degeneration/diagnosis/drug therapy/classification ; },
abstract = {PURPOSE: To develop a data-driven severity scoring system for age-related macular degeneration (AMD) that can generate distinct scores for exudative AMD (AMD-W) and nonexudative AMD (AMD-D) and that can be applied to routine clinical features captured in electronic medical record (EMR) data, in which complete data on features included in traditional scoring systems are rare.<br><br>DESIGN: Retrospective cohort study with external validation.<br><br>PARTICIPANTS: Data from participants in the Age-Related Eye Disease Study (AREDS), AREDS2, and the Eye Adult Changes in Thought (Eye ACT) study.<br><br>METHODS: Severity score models were developed for non-exudative ("dry") AMD (AMD-D) and exudative ("wet") AMD (AMD_W) based on confirmatory factor analysis (CFA) of data from AREDS and AREDS2. Models were applied to an independent cohort of the Eye ACT study whose longitudinal ophthalmic clinical data were extracted from an EMR capturing routine care, using natural language processing-based text mining algorithms.<br><br>MAIN OUTCOME MEASURES: Trajectories of AMD-D and AMD-W scores in the Eye ACT cohort and relationship with age and the onset of the first anti-VEGF treatment.<br><br>RESULTS: In the Eye ACT cohort, AMD-D and AMD-W scores showed a moderately positive correlation (Pearson 0.702, 95% confidence interval, 0.699-0.704). In 4412 eyes from 2248 participants in Eye ACT, which never received anti-VEGF, AMD-D scores increased slightly before the age of 80 years, followed by a steeper increase through the age of 90 years. In 220 eyes of 171 Eye ACT participants, which received anti-VEGF, most showed a pattern of gradually increasing AMD-W scores in the weeks or months before the anti-VEGF treatment.<br><br>CONCLUSIONS: The CFA-based scoring system enabled detailed assessments of both non-exudative and exudative severity using features collected in a routine clinical setting with ubiquitous missing data, in which standard AREDS scoring is not possible.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid40311520,
year = {2025},
author = {Dujardin, C and Habeler, W and Aprile, P and Dellaquila, A and Monville, C and Letourneur, D and Simon-Yarza, T},
title = {Engineered micro-structured biomimetic material for modelling the outer blood-retinal barrier.},
journal = {Biomaterials},
volume = {322},
number = {},
pages = {123357},
doi = {10.1016/j.biomaterials.2025.123357},
pmid = {40311520},
issn = {1878-5905},
mesh = {Humans ; *Biomimetic Materials/chemistry ; *Blood-Retinal Barrier/cytology ; Retinal Pigment Epithelium/cytology ; Coculture Techniques ; *Tissue Engineering/methods ; Induced Pluripotent Stem Cells/cytology ; Tissue Scaffolds/chemistry ; Endothelial Cells/cytology ; Choroid/cytology ; Models, Biological ; Porosity ; },
abstract = {The outer blood-retinal barrier (oBRB) is compromised in several retinal pathologies, such as age-related macular degeneration affecting over 200 million people worldwide. This 200-350 μm thick tissue includes the retinal pigment epithelium (RPE), the Bruch's membrane, and the vascularized choroid supplying the outer retina. Degeneration of the RPE and/or choroid leads to photoreceptor loss and, ultimately, blindness. Current in vitro co-culture oBRB models developed to better understand the diseases and to propose therapeutic alternatives are often simplistic, focusing on 2D cultures, or face limitations including non-physiological dimensions or low throughput. This study presents an innovative scaffold-driven approach to model the oBRB using a polysaccharide membrane engineered by freeze-drying. Our specific protocol allowed to mimic the oBRB structure, within physiological dimensions, generating a non-porous surface to culture the hiPSC-derived RPE monolayer, and an internal 3D porous structure for the choroidal network. Results showed that the inner porous structure promoted physiological self-organization of endothelial cells and pericytes. Our single-piece functional material allowed the cultivation of both RPE and choroidal compartments in close proximity, favoring cellular interactions, while maintaining them in their designated locations. This cyto-compatible, easy-to-use, and off-the-shelf membrane, produced at large amounts and low costs, provides a physiologically relevant biomaterial for oBRB tissue modelling.},
}
@article {pmid40310633,
year = {2025},
author = {Binder, KE and Bleidißel, N and Charbel Issa, P and Maier, M and Coulibaly, LM},
title = {Noninfectious Intraocular Inflammation After Intravitreal Aflibercept.},
journal = {JAMA ophthalmology},
volume = {143},
number = {6},
pages = {499-506},
pmid = {40310633},
issn = {2168-6173},
mesh = {Humans ; Intravitreal Injections/adverse effects ; Female ; Male ; Retrospective Studies ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Aged ; *Recombinant Fusion Proteins/adverse effects/administration &amp; dosage ; Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Visual Acuity ; Incidence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Macular Edema/drug therapy ; Middle Aged ; Aged, 80 and over ; *Endophthalmitis/chemically induced/epidemiology/diagnosis ; Diabetic Retinopathy/drug therapy ; Follow-Up Studies ; *Uveitis/chemically induced/epidemiology/diagnosis ; *Wet Macular Degeneration/drug therapy ; },
abstract = {IMPORTANCE: Aflibercept, 8 mg, is an anti-vascular endothelial growth factor (VEGF) formulation for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). While clinical trials report a comparable safety profile as aflibercept, 2 mg, clinical practice setting (so-called real-world) data on the incidence of intraocular inflammation (IOI) should be of value.<br><br>OBJECTIVE: To determine the clinical practice setting incidence of IOI after intravitreal injection of aflibercept, 8 mg, for nAMD and DME.<br><br>This retrospective case series involved a review of medical records at a single tertiary care center. Participants were all patients who received an intravitreal injection of aflibercept, 8 mg, for nAMD or DME from March 2024 to October 2024. Patients had received injections with other VEGF inhibitors before. Standard care included slitlamp examination before each injection and follow-up examination within 4 days after every injection.<br><br>EXPOSURE: IOI adverse events (AEs) after injections.<br><br>MAIN OUTCOMES AND MEASURES: Incidence of IOI after intravitreal injection of aflibercept, 8 mg. Secondary outcomes included the time point of IOI and best-corrected visual acuity (BCVA) during and after recovery of IOI.<br><br>RESULTS: Forty-one patients were treated with intravitreal aflibercept, 8 mg, injections: 23 with nAMD (56%) and 18 with DME (44%). Twenty-seven patients (66%) were male and 14 patients female (34%). A total of 136 intravitreal injections of aflibercept, 8 mg, were administered during the observation period. Five patients of 41 developed mild sterile IOI within 1 to 3 days after the intervention (incidence per injection, 3.7%; 95% CI, 1.6%-8.3%; incidence per patient, 12%; 95% CI, 5.3%-25.5%). Four patients had prior exposure to aflibercept, 8 mg, before the inflammation occurred; only 1 patient developed inflammation after the first dose. All patients were treated with local anti-inflammatory therapy (topical or subconjunctival corticosteroids), and 2 patients received additional systemic oral corticosteroids. No reduction of BCVA was observed after IOI-associated AEs receded.<br><br>CONCLUSIONS AND RELEVANCE: This analysis in a clinical practice setting revealed a more frequent occurrence of IOI-associated AEs compared with previous clinical trials. All observed cases showed a mild IOI, which resolved under anti-inflammatory therapy without loss of BCVA.},
}
@article {pmid40310551,
year = {2025},
author = {Pellegrini, M and Adamo, GG and Vivarelli, C and Sarti, L and Talli, PM and Nasini, F and Parmeggiani, F and Mura, M},
title = {Vitrectomy with macular peeling in eyes with vitreomacular interface disorders and nonexudative age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {8},
pages = {2203-2208},
pmid = {40310551},
issn = {1435-702X},
mesh = {Humans ; *Vitrectomy/methods ; Retrospective Studies ; Female ; Male ; *Visual Acuity ; Aged ; Tomography, Optical Coherence ; Follow-Up Studies ; *Macula Lutea/pathology/surgery ; *Macular Degeneration/diagnosis/surgery/complications ; Disease Progression ; *Vitreous Body/surgery/pathology ; Aged, 80 and over ; Middle Aged ; Treatment Outcome ; },
abstract = {BACKGROUND: The aim of the study was to assess the outcomes of pars plana vitrectomy and macular peeling for vitreomacular interface disorders in eyes with coexisting nonexudative age-related macular degeneration (AMD), and to compare the rate of AMD progression in operated and fellow eyes.<br><br>METHODS: This retrospective comparative study included patients with bilateral nonexudative AMD and unilateral vitreomacular interface disorder who underwent pars plana vitrectomy with internal limiting membrane peeling. Controlateral unoperated eyes were used as a control group. Cox proportional hazards regression analysis was used to compare the incidence of macular neovascularization, geographic atrophy and progression to late AMD in operated eyes and fellow eyes.<br><br>RESULTS: 142 eyes of 71 patients were included. The mean follow-up duration was 17.5&#x2009;&#xb1;&#x2009;15.5&#xa0;months. Best corrected visual acuity significantly improved in operated eyes (from 0.47&#x2009;&#xb1;&#x2009;0.25 to 0.21&#x2009;&#xb1;&#x2009;0.18 logMAR; p&#x2009;<&#x2009;0.001), while no significant difference was observed in fellow eyes (from 0.18&#x2009;&#xb1;&#x2009;0.22 to 0.33&#x2009;&#xb1;&#x2009;0.56 logMAR; p&#x2009;=&#x2009;0.055). Central retinal thickness improved in operated eyes (from 0402.9&#x2009;&#xb1;&#x2009;79.9 to 296.1&#x2009;&#xb1;&#x2009;48.4&#xa0;&#xb5;m; p&#x2009;<&#x2009;0.001), while no change in fellow eyes was observed (from 296.1&#x2009;&#xb1;&#x2009;48.4 to 312.7&#x2009;&#xb1;&#x2009;110.6&#xa0;&#xb5;m; p&#x2009;=&#x2009;0.205). Vitrectomy was not associated with the risk of developing macular neovascularization (hazard ratio [HR]&#x2009;=&#x2009;0.30; 95% confidence intervals (CI)&#x2009;=&#x2009;0.08-1.09; p&#x2009;=&#x2009;0.068); geographic atrophy (HR&#x2009;=&#x2009;1.01, 95% CI&#x2009;=&#x2009;0.32-3.12; p&#x2009;=&#x2009;0.990) nor progression to late AMD (HR&#x2009;=&#x2009;0.64, 95% CI&#x2009;=&#x2009;0.28-1.49; p&#x2009;=&#x2009;0.307).<br><br>CONCLUSIONS: Pars plana vitrectomy with macular peeling for vitreomacular interface disorders in eyes with coexisting nonexudative AMD is associated with positive visual and functional outcomes, with no shot-term increased risk of AMD progression.},
}
@article {pmid40310357,
year = {2025},
author = {Grün, M and Rothaus, K and Ziegler, M and Lange, C and Lommatzsch, A and Faatz, H},
title = {The Vascular Architecture of Macular Neovascularization in Age-Related Macular Degeneration as a Predictor of Therapy Requirements: A 3-Year Longitudinal Analysis.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
pmid = {40310357},
issn = {2075-4418},
abstract = {Background: Anti-Vascular Endothelial Growth Factor (VEGF) therapy is an effective therapy for improving and stabilizing the vision of patients with neovascular age-related macular degeneration (nAMD). However, the treatment requirements, particularly the number of intraocular injections, can vary significantly among patients. This study aimed to analyze the vascular characteristics of macular neovascularizations (MNVs) to identify potential biomarkers that could predict the required injection frequency throughout the disease course. Methods: In all patients, the initial diagnosis of nAMD was confirmed using optic coherence tomography (OCT), fluorescein angiography, and OCT angiography (OCTA). MNVs detected using OCTA were subjected to quantitative vascular analysis of their area, total vascular length (sumL), fractal dimension (FD), and flow density. These results were then correlated with the number of intravitreal anti-VEGF treatments administered during the first 3 years of treatment. Additionally, the relationship between the parameters and visual acuity progression was analyzed. Results: A total of 68 treatment-naïve eyes were included in the study, comprising 31 eyes with type 1 MNV, 19 eyes with type 2 MNV, and 18 eyes with type 3 MNV. The average MNV area at baseline was 1.11 mm[2] ± 1.18 mm[2], the mean total vascular length was 12.95 mm ± 14.24 mm, the mean fractal dimension was 1.26 ± 0.14, and the mean flow density was 41.19 ± 5.87. On average, patients in our cohort received 19.8 ± 8.5 intravitreal injections (IVIs). A significant correlation was found between the number of administered IVIs in the first 3 treatment years and the MNV area (p < 0.005), sumL (p < 0.005), and FD (p < 0.05), while no correlation was found with flow density. Additionally, there was no significant association between MNV type and treatment requirements, nor between MNV vascular architecture and visual acuity progression. Conclusions: The results suggest that the specific vascular structure of untreated MNV may serve as a predictor of long-term treatment demand. With the emergence of new drug classes and advancements in imaging techniques, these parameters could offer valuable insights for forecasting treatment requirements.},
}
@article {pmid40308919,
year = {2025},
author = {Liu, J and Wang, B and Li, Q},
title = {Machine learning model for age related macular degeneration based on pesticides: the National Health and Nutrition Examination Survey 2007-2008.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1561913},
pmid = {40308919},
issn = {2296-2565},
mesh = {Humans ; *Machine Learning ; *Macular Degeneration/epidemiology/chemically induced ; Nutrition Surveys ; *Pesticides/adverse effects ; Male ; Female ; Aged ; Middle Aged ; *Environmental Exposure/adverse effects/statistics &amp; numerical data ; United States/epidemiology ; },
abstract = {Age-related macular degeneration (AMD) is the most common cause of irreversible deterioration of vision in older adults. Previous studies have found that exposure to pesticides can lead to a worsening of AMD. In this paper, information on pesticide exposure and AMD from the National Health and Nutrition Examination Survey (NHANES) database was used to divide the data into a training set and a validation set. Firstly, the correlation between the variables in the model is analyzed. The model is then built using nine machine learning algorithms and verified on a validation set. Finally, it is found that the random forest model has high predictive value, and its Receiver Operating Characteristic (ROC) value is 0.75. Finally, SHapley additive interpretation (SHAP) analysis was used to rank the importance of each variable in the random forest model, and it was found that chlorpyrifos and malathion had quite significant effects on the occurrence and development of AMD.},
}
@article {pmid40308329,
year = {2025},
author = {Wu, Z and De Zanet, S and Blair, JPM and Guymer, RH},
title = {Loss of OCT Outer Retinal Bands as Potential Clinical Trial Endpoints in Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100769},
pmid = {40308329},
issn = {2666-9145},
abstract = {PURPOSE: To understand the potential utility of evaluating loss of the outer retinal bands on OCT B-scans as outcome measures for early interventional trials in age-related macular degeneration (AMD).<br><br>DESIGN: An observational study.<br><br>PARTICIPANTS: Two hundred eighty eyes from 140 participants with bilateral large drusen.<br><br>METHODS: All participants underwent OCT imaging, color fundus photography, and microperimetry testing at 6-monthly intervals up to 36 months. The extent of loss of the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE) bands on OCT was derived in the central 5-mm diameter, and within 5 equiareal sectors in the central 3.6-mm diameter where microperimetry testing was performed.<br><br>MAIN OUTCOME MEASURES: The potential utility of the OCT outer retinal bands was examined based on their performance at capturing longitudinal changes according to the coefficient of variation (CoV; lower values indicating better performance) and their association with visual sensitivity loss.<br><br>RESULTS: Overall, the extent of loss of all 3 OCT bands increased significantly over time (P&#xa0;<&#xa0;0.001), with a significant change from baseline first detected at 12 months for ELM and EZ loss and at 24 months for RPE loss (P&#xa0;&#x2264;&#xa0;0.005 for all). Changes in the ELM, EZ, and RPE loss were all individually associated with change in mean sensitivity, percentage of locations showing a &#x2265;7&#xa0;decibels loss from baseline, and change in percentage of deep visual sensitivity defects at each corresponding sector tested on microperimetry (&#x2264;10&#xa0;dB; P&#xa0;<&#xa0;0.001 for all). The CoV of the rate of ELM and EZ loss was lower than RPE loss (P&#xa0;<&#xa0;0.001 for both), and lower for EZ compared with ELM loss (P&#xa0;<&#xa0;0.001).<br><br>CONCLUSIONS: The extent of loss of the outer retinal bands on OCT increased significantly over time in a cohort with intermediate AMD that was associated with changes in visual sensitivity, and measurements of EZ loss had the highest performance for capturing longitudinal changes. These findings highlight the potential utility of these parameters for evaluating interventions in the early stages of AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40307700,
year = {2025},
author = {Blasiak, J and Pawlowska, E and Helotera, H and Ionov, M and Derwich, M and Kaarniranta, K},
title = {Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration.},
journal = {Cellular &amp; molecular biology letters},
volume = {30},
number = {1},
pages = {54},
pmid = {40307700},
issn = {1689-1392},
mesh = {Humans ; *Autophagy ; Fibrosis ; *Macular Degeneration/pathology/metabolism ; Animals ; Epithelial-Mesenchymal Transition ; *Retina/pathology ; Retinal Pigment Epithelium/pathology/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is an eye disease that can lead to legal blindness and vision loss. In its advanced stages, it is classified into dry and neovascular AMD. In neovascular AMD, the formation of new blood vessels disrupts the structure of the retina and induces an inflammatory response. Treatment for neovascular AMD involves antibodies and fusion proteins targeting vascular endothelial growth factor A (VEGFA) and its receptors to inhibit neovascularization and slow vision loss. However, a fraction of patients with neovascular AMD do not respond to therapy. Many of these patients exhibit a subretinal fibrotic scar. Thus, retinal fibrosis may contribute to resistance against anti-VEGFA therapy and the cause of irreversible vision loss in neovascular AMD patients. Retinal pigment epithelium cells, choroidal fibroblasts, and retinal glial cells are crucial in the development of the fibrotic scar as they can undergo a mesenchymal transition mediated by transforming growth factor beta and other molecules, leading to their transdifferentiation into myofibroblasts, which are key players in subretinal fibrosis. Autophagy, a process that removes cellular debris and contributes to the pathogenesis of AMD, regardless of its type, may be stimulated by epithelial-mesenchymal transition and later inhibited. The mesenchymal transition of retinal cells and the dysfunction of the extracellular matrix-the two main aspects of fibrotic scar formation-are associated with impaired autophagy. Nonetheless, the causal relationship between autophagy and subretinal fibrosis remains unknown. This narrative/perspective review presents information on neovascular AMD, subretinal fibrosis, and autophagy, arguing that impaired autophagy may be significant for fibrosis-related resistance to anti-VEGFA therapy in neovascular AMD.},
}
@article {pmid40307638,
year = {2025},
author = {Neiteler, A and Borooah, S and Ross, JA},
title = {Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelial Cells for the Study of Macular Degeneration.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2924},
number = {},
pages = {101-112},
pmid = {40307638},
issn = {1940-6029},
mesh = {*Induced Pluripotent Stem Cells/cytology/metabolism ; *Retinal Pigment Epithelium/cytology/metabolism ; Humans ; *Macular Degeneration/pathology/metabolism ; Cell Differentiation ; *Cell Culture Techniques/methods ; Phagocytosis ; Cells, Cultured ; Epithelial Cells/cytology/metabolism ; },
abstract = {We have developed a method to reliably generate retinal pigment epithelium (RPE) in bulk from human induced pluripotent stem cells (iPSCs). These iPSC-RPE showed a typical RPE-like morphology with pigmentation and expressed typical RPE markers. The iPSC-RPE also show a transepithelial electrical resistance and can phagocytose photoreceptor outer segments, indicating that they are also functional. Large quantities of iPSC-RPE can be generated with this method through serial expansion for disease modeling and high-throughput screenings.},
}
@article {pmid40305470,
year = {2025},
author = {Dow, E and Kearney, S and Day, M},
title = {Absolute Risks and Decision Tools for Communicating the Risks of Visual Impairment From Myopia-Related Diseases.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {82},
pmid = {40305470},
issn = {1552-5783},
mesh = {Humans ; *Myopia/complications ; *Vision Disorders/etiology/epidemiology ; *Glaucoma, Open-Angle/etiology/complications/epidemiology ; Risk Assessment/methods ; *Macular Degeneration/etiology/complications/epidemiology ; *Retinal Detachment/etiology/epidemiology ; Risk Factors ; *Decision Support Techniques ; Adult ; },
abstract = {PURPOSE: The risks of developing myopia complications are frequently reported in relative terms, which can be misleading. This study provides absolute risk estimates of visual impairment (VI) from myopia-related diseases.<br><br>METHODS: A critical integrative review provided data on frequency of myopic macular degeneration (MMD), primary open-angle glaucoma (POAG), rhegmatogenous retinal detachment (RRD), and associated VI in predominantly White and East Asian populations. The absolute risks of persons over 40 years of age with no myopia, low myopia (-2.00 D), or high myopia (-6.00 D) developing VI from each myopia-related disease were calculated by multiplying the proportion of each refractive group with the disease by the rate of VI. The sum of the risks of VI from MMD, POAG, and RRD provided an estimate of VI risk from any of these three myopia-related diseases in adults over 40 years old.<br><br>RESULTS: VI from MMD, POAG, or RRD combined is expected in 0.4 in 100, 1.4 in 100, and 6.8 in 100 of White persons with no myopia, low myopia, or high myopia, respectively. The same risks in an East Asian population are 0.5 in 100, 2.4 in 100 and 10.3 in 100 in persons with no myopia, low myopia, or high myopia, respectively.<br><br>CONCLUSIONS: Absolute risks are provided to enable balanced discussions of the future risk that a child may have in developing VI from myopia-related diseases when considering myopia management. These estimates should be put into context using decision tools and balanced statements providing information on the likelihood of both developing VI and not developing VI.},
}
@article {pmid40305469,
year = {2025},
author = {Yang, Y and Shen, J and Li, Y and Chen, X and Liu, G and Lu, P},
title = {AZGP1 Attenuates Subretinal Fibrosis and Inhibits Epithelial-Mesenchymal Transition by Blocking the PI3K/AKT Signaling Pathway.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {83},
pmid = {40305469},
issn = {1552-5783},
mesh = {Animals ; *Epithelial-Mesenchymal Transition/drug effects ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; Fibrosis/metabolism ; Disease Models, Animal ; *Proto-Oncogene Proteins c-akt/metabolism ; Humans ; *Phosphatidylinositol 3-Kinases/metabolism ; Retinal Pigment Epithelium/pathology/metabolism ; Intravitreal Injections ; *Carrier Proteins/genetics/pharmacology ; Male ; Zn-Alpha-2-Glycoprotein ; },
abstract = {PURPOSE: Subretinal fibrosis (SRF) represents a significant contributor to irreversible vision loss in patients with neovascular age-related macular degeneration (nAMD). This study aimed to elucidate the underlying mechanism of SRF and identify potential therapeutic targets.<br><br>METHODS: The SRF model was established using a two-stage laser-induced protocol in C57BL/6J mice. RNA-seq analysis was conducted to identify differentially expressed genes (DEGs) at 10 days and 30 days post-second laser. Quantitative RT-PCR was used to validate the expression levels of selected DEGs including zinc-alpha-2-glycoprotein 1 (AZGP1). Recombinant AZGP1 (rAZGP1) was intravitreally administrated to investigate its effects on SRF. The ARPE-19 cells were used to demonstrate the role of AZGP1 in modulating epithelial-mesenchymal transition (EMT).<br><br>RESULTS: RNA-seq of RPE/choroid complex identified a total of 66 DEGs between samples collected at 10 days and 30 days post-second laser compared with controls (log2(fold change) &#x2265; 1, false discovery rate [FDR] < 0.05), with Azgp1 being one of the most significant downregulated genes. Intravitreal injection of rAZGP1 markedly reduced collagen I and CD31 positive areas in RPE/choroid flat-mounts. Co-localization of AZGP1 and RPE65 was observed in patients with nAMD (GSE135922) and SRF mouse models. Treatment with rAZGP1 resulted in significantly lower expressions of collagen I, &#x3b1;-SMA, and fibronectin in ARPE-19 cells after TGF&#x3b2;1 induction. Both knockdown and overexpression studies demonstrated that AZGP1 regulated the PI3K/AKT signaling pathway within ARPE-19 cells.<br><br>CONCLUSIONS: The abnormal expression pattern of AZGP1 is critical for the development of SRF. Exogenous supplementation with AZGP1 may represent a promising strategy for ameliorating SRF by inhibiting EMT within RPE through the PI3K/AKT pathway.},
}
@article {pmid40305267,
year = {2025},
author = {Liao, ZY and Hung, CY and Hsu, YJ and Liang, IC and Chen, YC and Sung, CH and Hung, CF},
title = {Phlorizin Protects Against Oxidative Stress and Inflammation in Age-Related Macular Degeneration Model.},
journal = {Biomolecules},
volume = {15},
number = {4},
pages = {},
pmid = {40305267},
issn = {2218-273X},
support = {113-2320-B-030-007-MY3//National Science and Technology Council/ ; 110-SKH-FJU-531 01//Shin Kong Wu Ho-Su Memorial Hospital/ ; },
mesh = {*Oxidative Stress/drug effects ; Animals ; Mice ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Inflammation/drug therapy/metabolism ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; *Phlorhizin/pharmacology ; Cell Line ; Choroidal Neovascularization/drug therapy/metabolism/pathology ; Cell Survival/drug effects ; Retinal Pigment Epithelium/drug effects/metabolism ; NF-kappa B/metabolism ; Antioxidants/pharmacology ; *Anti-Inflammatory Agents/pharmacology ; Mice, Inbred C57BL ; Cytokines/metabolism ; Male ; },
abstract = {BACKGROUND: Sweet Tea (Lithocarpus polystachyus Rehd.), a traditional ethnobotanical medicine, contains phlorizin, a dihydrochalcone compound with antioxidative and anti-inflammatory properties. Given the critical role of oxidative stress and inflammation in age-related macular degeneration (AMD), this study tested the hypothesis that phlorizin mitigates oxidative damage and inflammation in AMD models, thereby offering therapeutic potential.<br><br>MATERIALS AND METHODS: Adult retinal pigmented epithelial cells (ARPE-19) were pre-treated with phlorizin (0.01-0.1 &#x3bc;M) and subjected to oxidative stress induced by ultraviolet A (UVA) radiation or sodium iodate (NaIO3). Cell viability, reactive oxygen species (ROS) production, MAPK/NF-&#x3ba;B signaling, and the level of pro-inflammatory cytokines (IL-1&#x3b2;, IL-6, TNF-&#x3b1;) and pro-angiogenic factors (VEGF, MMP2, MMP9) expression were assessed using MTT assays, fluorescence imaging, Western blotting, and RT-qPCR. In vivo, a laser-induced choroidal neovascularization (CNV) mouse model was used to evaluate phlorizin's effects on CNV formation and vascular leakage via fundus photography and fluorescence angiography.<br><br>RESULT: Phlorizin significantly enhanced cell viability, reduced ROS production, inhibited MAPK/NF-&#x3ba;B activation, and downregulated inflammatory and angiogenic mediators. In vivo studies confirmed the reduced CNV formation and vascular leakage following the phlorizin treatment.<br><br>CONCLUSIONS: Phlorizin demonstrated significant protective effects against oxidative stress and inflammation, highlighting its therapeutic potential for treating AMD.},
}
@article {pmid40303372,
year = {2025},
author = {An, N and Zeng, B and Liu, Z and Zhang, C and Liao, H and Liu, D and Qin, B},
title = {Red blood cell distribution width-to-albumin ratio and its association with age-related macular degeneration: a population-based cross-sectional study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1510756},
pmid = {40303372},
issn = {2296-858X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of central vision impairment in middle-aged and older individuals. There is substantial evidence that AMD is associated with inflammation. The study aimed to investigate the association between the inflammatory marker, red blood cell distribution width/albumin ratio (RAR), and AMD.<br><br>METHODS: Our study included 5,370 participants aged 40&#x202f;years and older, using NHANES data from 2005 to 2008. Multivariable logistic regression analysis was conducted to examine the relationship between RAR and AMD in the study. Smooth curves and the piecewise linear regression model were used to determine whether the correlation was linear or non-linear. Additionally, subgroup analysis and interaction testing were performed.<br><br>RESULTS: We found a positive linear correlation between RAR and AMD, even after adjusting for covariates. Each unit increase in RAR corresponded to a 30% increase in the odds of AMD prevalence (OR&#x202f;=&#x202f;1.3; 95% CI, 1.0-1.6). The odds of AMD prevalence were 1.7 times greater in the highest quintile (Q5) group than in the lowest quintile (Q1) group (OR&#x202f;=&#x202f;1.7; 95% CI, 1.2-2.5). Higher RAR values, compared to lower values, were significantly associated with increased odds of AMD prevalence (p trend < 0.05). Subgroup analyses and interaction tests confirmed the stability of the findings.<br><br>CONCLUSION: This study found that there is a positive linear correlation between RAR and the odds of AMD prevalence in United States adults. Further research is necessary to clarify the specific physiological mechanisms underlying the relationship between RAR and AMD.},
}
@article {pmid40302430,
year = {2025},
author = {Zhan, Z and Li, Z},
title = {Trends in the global disease burden of age-related macular degeneration from 1990 to 2021.},
journal = {European journal of ophthalmology},
volume = {35},
number = {5},
pages = {1627-1636},
doi = {10.1177/11206721251339231},
pmid = {40302430},
issn = {1724-6016},
mesh = {Humans ; Male ; Female ; *Macular Degeneration/epidemiology ; Aged ; Global Health ; Global Burden of Disease/trends ; Disability-Adjusted Life Years/trends ; Aged, 80 and over ; Risk Factors ; Middle Aged ; Age Distribution ; Sex Distribution ; Quality-Adjusted Life Years ; Incidence ; },
abstract = {AimTo investigate the global disease burden of age-related macular degeneration (AMD) from 1990 to 2021 using data from the Global Burden of Diseases 2021 database.MethodsWe recorded disability-adjusted life years (DALYs) and rates and estimated annual percentage changes (EAPCs) in AMD stratified by sex, age, sociodemographic index (SDI), geographic region, country, and risk factor.ResultsGlobally, the number of AMD-associated DALYs increased from 302,902 in 1990 to 578,020 in 2021, while the age-standardized rate (ASR) of DALYs decreased by 19.089% from 1990 to 2021, with an EAPC of -0.942 (95% CI, -1.010-0.873). During this period, males had fewer DALYs and lower ASRs than did females, and the ASR decreased with decreasing age. In 2021, the low-SDI region had the highest ASR (10.082 per 100,000 individuals) and the slowest ASR decrease (EAPC: -0.652, 95% CI, -0.708--0.595). East Asia had the most DALYs (154,300.168), and Western Sub-Saharan Africa had the highest ASR (14.735 per 100,000 individuals). From 1990 to 2021, all 21 regions experienced increased DALYs, while most regions, except for Central Sub-Saharan Africa and Southern Sub-Saharan Africa, experienced decreases in the ASR. China had the most DALYs (153,219.726) in 2021. The proportion of DALYs attributable to smoking in patients with AMD decreased globally and across all SDI regions from 1990 to 2021.ConclusionOver the past 32 years, AMD has remained a significant health concern, particularly affecting females, older individuals, and individuals living in lower-SDI regions, with a global decline in smoking-related AMD DALYs.},
}
@article {pmid40301864,
year = {2025},
author = {Jang, W and Kim, Y and Kim, H},
title = {Correction: Association between the dietary omega-6 to omega-3 fatty acid ratio and age-related macular degeneration in Korean adults.},
journal = {Nutrition journal},
volume = {24},
number = {1},
pages = {68},
pmid = {40301864},
issn = {1475-2891},
}
@article {pmid40301288,
year = {2025},
author = {Zhen, B and Qi, Y and Tang, Z and Liu, C and Zhao, S and Yu, Y and Liu, Q},
title = {Low-Rank Fine-Tuning Meets Cross-modal Analysis: A Robust Framework for Age-Related Macular Degeneration Categorization.},
journal = {Journal of imaging informatics in medicine},
volume = {},
number = {},
pages = {},
pmid = {40301288},
issn = {2948-2933},
support = {22019821001//Beijing Municipal Education Commission/ ; 2025J00105//National College Students Innovation and Entrepreneurship Training Program/ ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent retinal degenerative disease among the elderly and is a major cause of irreversible vision loss worldwide. Although color fundus photography (CFP) and optical coherence tomography (OCT) are widely used for AMD diagnosis, information from a single modal is inadequate to fully capture the complex pathological features of AMD. To address this, this study proposes an innovative multi-modal deep learning framework that fine-tunes pre-trained single-modal retinal models for efficient application in multi-modal AMD categorization tasks. Specifically, two independent vision transformer models are used to extract features from CFP and OCT images, followed by deep canonical correlation analysis (DCCA) to perform nonlinear mapping and fusion of features from both modalities, maximizing cross-modal feature correlation. Moreover, to reduce the computational complexity of multi-modal integration, we introduce the low-rank adaptation (LoRA) technique, which uses low-rank decomposition of parameter matrices, achieving superior performance compared to full fine-tuning with only about 0.49% of the trainable parameters. Experimental results on the public dataset MMC-AMD validate the framework's effectiveness. The proposed model achieves an overall F1-score of 0.948, AUC-ROC of 0.991, and accuracy of 0.949, significantly outperforming existing single-modal and multi-modal baseline models, particularly excelling in recognizing complex pathological categories.},
}
@article {pmid40300720,
year = {2025},
author = {Ozen, A and Can, S and Sefer, AP and Ozturk, NK and Colak, BC},
title = {Complement dysregulation at lymphatics.},
journal = {The Journal of allergy and clinical immunology},
volume = {156},
number = {2},
pages = {205-214},
doi = {10.1016/j.jaci.2025.04.020},
pmid = {40300720},
issn = {1097-6825},
mesh = {Humans ; *Complement System Proteins/immunology/metabolism ; Complement Activation ; Animals ; CD55 Antigens/genetics ; *Lymphatic System/immunology ; },
abstract = {The complement system is a central component of innate immunity, orchestrating pathogen clearance while regulating inflammation, tissue repair, and homeostasis. Its activation is tightly controlled by multiple inhibitors to prevent self-damage. However, complement dysregulation is implicated in numerous organ-specific diseases, including paroxysmal nocturnal hemoglobinuria (erythrocytes), atypical hemolytic uremic syndrome (kidneys), and age-related macular degeneration (eyes). Recent discoveries have revealed that complement hyperactivation also drives lymphatic dysfunction, most notably in CHAPLE (CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy) disease-a rare pediatric disorder caused by biallelic CD55 mutations. Impaired regulation of C3 and C5 convertases leads to unchecked complement and coagulation activation, resulting in membrane attack complex deposition, severe intestinal lymphangiectasia, and protein-losing enteropathy. Patients typically present with hypoalbuminemia, edema, gastrointestinal symptoms, growth retardation, and recurrent thromboembolic events, reflecting a severe thrombophilic phenotype. C5-blocking antibodies, including pozelimab and eculizumab, transformed CHAPLE management. In a phase 2/3 study, pozelimab led to normalization of serum albumin levels and notable reductions in hospitalizations and transfusion needs, leading to Food and Drug Administration approval. Emerging evidence suggests that complement-driven protein-losing enteropathy may also arise in other pathological contexts, expanding the clinical impact of complement dysregulation. As research progresses, novel diagnostic and therapeutic strategies are expected to emerge for a broader spectrum of complement-mediated lymphatic disorders.},
}
@article {pmid40299661,
year = {2025},
author = {Zhao, N and Li, S and Wu, H and Wei, D and Pu, N and Wang, K and Liu, Y and Tao, Y and Song, Z},
title = {Ferroptosis: An Energetic Villain of Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {13},
number = {4},
pages = {},
pmid = {40299661},
issn = {2227-9059},
support = {221100310200//Science and Technology Major Project of Henan Province/ ; },
abstract = {Iron homeostasis plays an important role in maintaining cellular homeostasis; however, excessive iron can promote the production of reactive oxygen species (ROS). Ferroptosis is iron-dependent programmed cell death that is characterized by excessive iron accumulation, elevated lipid peroxides, and the overproduction of ROS. The maintenance of iron homeostasis is contingent upon the activity of the transferrin receptor (TfR), ferritin (Ft), and ferroportin (FPn). In the retina, iron accumulation and lipid peroxidation can contribute to the development of age-related macular degeneration (AMD). This phenomenon can be explained by the occurrence of the Fenton reaction, in which the interaction between divalent iron and hydrogen peroxide leads to the generation of highly reactive hydroxyl radicals. The hydroxyl radicals exhibit a propensity to attack proteins, lipids, nucleic acids, and carbohydrates, thereby instigating oxidative damage and promoting lipid peroxidation. Ultimately, these processes culminate in cell death and retinal degeneration. In this context, a comprehensive understanding of the exact mechanisms underlying ferroptosis may hold significant importance for developing therapeutic interventions. This review summarizes recent findings on iron metabolism, cellular ferroptosis, and lipid metabolism in the aging retina. We also introduce developments in the therapeutic strategies using iron chelating agents. Further refinements of these knowledges would deepen our comprehension of the pathophysiology of AMD and advance the clinical management of degenerative retinopathy. A comprehensive search strategy was employed to identify relevant studies on the role of ferroptosis in AMD. We performed systematic searches of the PubMed and Web of Science electronic databases from inception to the current date. The keywords used in the search included "ferroptosis", "AMD", "age-related macular degeneration", "iron metabolism", "oxidative stress", and "ferroptosis pathways". Peer-reviewed articles, including original research, reviews, meta-analyses, and clinical studies, were included in this paper, with a focus on the molecular mechanisms of ferroptosis in AMDs. Studies not directly related to ferroptosis, iron metabolism, or oxidative stress in the context of AMD were excluded. Furthermore, articles that lacked sufficient data or were not peer-reviewed (e.g., conference abstracts, editorials, or opinion pieces) were not considered.},
}
@article {pmid40298749,
year = {2025},
author = {Bulla, MC and Lavinsky, D},
title = {Real-world safety and efficacy of Anti-VEGF treatment in Brazil.},
journal = {Arquivos brasileiros de oftalmologia},
volume = {88},
number = {4},
pages = {e20240277},
doi = {10.5935/0004-2749.2024-0277},
pmid = {40298749},
issn = {1678-2925},
mesh = {Humans ; Retrospective Studies ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects/therapeutic use ; Female ; Male ; Intravitreal Injections ; Brazil ; Middle Aged ; Treatment Outcome ; Recombinant Fusion Proteins/administration &amp; dosage/adverse effects/therapeutic use ; Visual Acuity/drug effects ; Ranibizumab/administration &amp; dosage/adverse effects/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Aged ; Macular Edema/drug therapy ; Bevacizumab/administration &amp; dosage/adverse effects/therapeutic use ; Diabetic Retinopathy/drug therapy ; Retinal Vein Occlusion/drug therapy ; Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: This retrospective study evaluated the safety and efficacy of real-world antiangiogenic therapy for ocular conditions in the private healthcare sector in southern Brazil.<br><br>METHODS: Medical records from patients who underwent intravitreal anti-vascular endothelial growth factor injections over the past 12 years were reviewed retrospectively. Data collection included the primary diagnoses, drugs administered, injection techniques, adverse effects, and treatment efficacy. Efficacy was assessed by comparing preand posttreatment visual acuity and central subfield thickness in eyes with followup exceeding 2 years.<br><br>RESULTS: A total of 1,024 patients, 1,310 treated eyes, and 11,377 injections were analyzed. The injections included aflibercept (6,833), ranibizumab (3,692), bevacizumab (843), and brolucizumab (9), administered either bilaterally (3,696) or unilaterally (7,681). The most common diagnoses were diabetic macular edema, exudative age-related macular degeneration, retinal vein occlusion related macular edema, and proliferative diabetic retinopathy. No endophthalmitis cases were reported. Vitritis with transient visual acuity loss occurred in two cases following aflibercept injections. One retinal detachment case was successfully treated with vitrectomy. The median number of injections per patient was 6 (IQR [interquartile range], 3-13). Among 445 eyes from 328 patients with followup over 2 years (median, 4.05 years; IQR, 2.89-6.29), there was a significant improvement in best-corrected visual acuity from 0.3 to 0.4 (Snellen) (p<0.001) and a reduction in central subfield thickness from 361 to 267 microns (p<0.001). CST comparisons included patients with age-related macular degeneration, diabetic macular edema, and retinal vein occlusion related macular edema.<br><br>CONCLUSION: This real-world study, the largest of its kind in Brazil, confirms the safety and efficacy of antiangiogenic therapies in the southern Brazilian private healthcare system. The findings highlight a low incidence of severe adverse events and outcomes consistent with global studies, supporting the ongoing use of antiangiogenic agents as effective and well-tolerated treatments for various ocular conditions in developing countries.},
}
@article {pmid40297766,
year = {2025},
author = {Hogan, B and Mehta, N and Caldwell, AS and Marin, AI and Gill, ZS and Liske-Cervantes, A and Mathias, MT and Manoharan, N and Palestine, AG and Forest, TEC and Mandava, N and Lynch, AM and Patnaik, JL},
title = {Risk of progression in intermediate age-related macular degeneration among patients using systemic beta-blockers.},
journal = {Frontiers in ophthalmology},
volume = {5},
number = {},
pages = {1535791},
pmid = {40297766},
issn = {2674-0826},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: This study aims to determine whether systemic beta-blocker use over time influences the progression from intermediate to advanced age-related macular degeneration (AMD).<br><br>METHODS: This prospective cohort study utilized data from the University of Colorado Age-Related Macular Degeneration Registry at the UCHealth Sue Anschutz-Rodgers Eye Center. Patients with intermediate AMD (iAMD) enrolled between October 2014 and November 2021. At enrollment, patient demographics and medication history were recorded. Beta-blocker use was assessed at enrollment and at each follow-up visit. Participants were asked to return annually for imaging, and images were classified as either intermediate AMD or conversion to advanced non-neovascular (NNV) AMD or neovascular (NV) AMD by two vitreoretinal specialists using multimodal imaging. Time to conversion was analyzed using Kaplan-Meier curves for each advanced AMD phenotype and for overall conversion, stratified by beta-blocker status. Progression from intermediate to advanced AMD (NNV or NV) was determined using multimodal imaging, including optical coherence tomography, color fundus photography, and fundus autofluorescence of the posterior pole.<br><br>RESULTS: A total of 292 patients were included in the study, with 22.6% using a systemic beta-blocker and 36.6% (n = 107) progressing from iAMD to advanced AMD in at least one eye. Patients on a beta-blocker at enrollment were more likely to convert to NV AMD (HR: 1.92 [95% CI: 1.04, 3.55], p-value = 0.036), but this association was no longer significant after adjusting for age and treated hypertension. No significant differences were observed in conversion to advanced NNV or any advanced AMD between groups (all p > 0.05).<br><br>CONCLUSIONS: In adjusted analyses, systemic beta-blocker use was not significantly associated with the risk of progression from iAMD to advanced NV or NNV AMD.},
}
@article {pmid40296985,
year = {2025},
author = {Sakai, D and Mandai, M and Hirami, Y and Yamamoto, M and Ito, SI and Igarashi, S and Yokota, S and Uyama, H and Fujihara, M and Maeda, A and Terada, M and Nishida, M and Shibata, Y and Hayashi, N and Iseki, K and Miura, T and Kajita, K and Ishida, M and Sugita, S and Maeda, T and Takahashi, M and Kurimoto, Y},
title = {Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100770},
pmid = {40296985},
issn = {2666-9145},
abstract = {PURPOSE: To explore the safety and efficacy of the allogeneic induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) strip transplantation for patients with RPE degeneration.<br><br>DESIGN: Single-arm, open-label, interventional study.<br><br>PARTICIPANTS: Three eyes from 3 patients clinically diagnosed with RPE impairment disease; 1 patient had dry age-related macular degeneration (AMD), and remaining 2 patients had MERTK-associated retinitis pigmentosa.<br><br>INTERVENTION: Allogeneic iPSC-derived RPE strip transplantation was performed by a 25-gauge pars plana vitrectomy. The RPE strips were prepared by incubating iPSC-derived RPE cells in 2-mm-wide grooves in the mold. Artificial retinal detachment was generated using a 38-gauge subretinal cannula, and the RPE strips were injected into the retinal bleb using a 31-gauge cannula with the maximum graft dose limited to 2 strips.<br><br>MAIN OUTCOME MEASURES: The reduction of RPE abnormal area by the engraftment of transplanted allogeneic iPSC-derived RPE cells, which was measured by analyzing fluorescein angiography with an automated evaluation program at pretransplantation and up to 52 weeks posttransplantation.<br><br>RESULTS: The primary endpoint of reducing abnormal areas of RPE through the survival of the transplanted graft cells was achieved in all patients at 52 weeks posttransplantation. Visual function assessments confirmed significant vision-related quality of life improvement and potential retinal sensitivity restoration in 1 patient with dry AMD. The successful subretinal delivery of the iPSC-derived RPE strips was confirmed during and immediately after surgery. The engraftment of RPE cells migrated out from the strips was observed using polarization-sensitive OCT specifically and visualized as characteristic hexagonal cells via adaptive optics imaging in all patients. While no serious adverse events occurred, suspected immune reactions to graft cells and epiretinal membrane formation were observed in 1 patient each.<br><br>CONCLUSIONS: A decrease in the RPE abnormal area by reliable delivery of allogeneic iPSC-derived RPE strips was achieved in all 3 cases with no serious adverse events. Further long-term studies and larger cohorts with better preoperative vision are warranted to evaluate the safety and efficacy of RPE strip transplantation.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40295235,
year = {2025},
author = {Liu, D and Li, C and Cui, L and Li, S},
title = {Short-term comparison of switching to faricimab from other anti-VEGF agents in neovascular age-related macular degeneration patients: A retrospective study.},
journal = {Medicine},
volume = {104},
number = {17},
pages = {e42002},
pmid = {40295235},
issn = {1536-5964},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Visual Acuity/drug effects ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Ranibizumab/therapeutic use ; *Drug Substitution ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Aged, 80 and over ; Receptors, Vascular Endothelial Growth Factor ; Antibodies, Bispecific ; },
abstract = {In order to evaluate the short-term outcomes of switching to faricimab from other anti-vascular endothelial growth factor (VEGF) agents in Chinese patients with neovascular age-related macular degeneration (nAMD). This was a retrospective, observational study involving patients with nAMD who had insufficient response to previous anti-VEGF therapy and were switched to Faricimab. Best-corrected visual acuity, central macular thickness, and pigment epithelium detachment (PED) changes were recorded at baseline and after one month of treatment. Data were analyzed using paired t-tests to compare outcomes before and after the switch. This study included 35 eyes from 35 patients (mean age 69.74 ± 11.22 years) who were switched to Faricimab after an average of 6.27 ± 3.41 prior anti-VEGF injections for nAMD. While best-corrected visual acuity showed no significant improvement after one month (P = .06), significant reductions were observed in mean central macular thickness (P < .001), PED height (P < .001), PED volume (P < .001), presence of subretinal fluid (P = .03), and intraretinal fluid (P = .04). Additionally, the presence of PED decreased from 60% at baseline to 45.71% after one month (P = .02). No new safety concerns were identified during the study period. Switching to faricimab from other anti-VEGF agents resulted in significant short-term improvements in both visual and anatomical outcomes, including reduced central macular thickness, pigment epithelium detachment, and subretinal and intraretinal fluid. These findings suggest that Faricimab may offer a beneficial alternative for patients with an insufficient response to prior anti-VEGF therapies. Long-term follow-up studies are necessary to confirm the durability and long-term benefits of this treatment.},
}
@article {pmid40294859,
year = {2025},
author = {Rowen, D and Carlton, J and McDool, E and Holz, FG and Zakaria, N and Terheyden, JH and Finger, RP and , },
title = {Psychometric Performance of a New Condition-Specific Preference-Weighted Measure, Vision Impairment in Low Luminance-Utility Index, and EQ-5D-5L in Patients With Age-Related Macular Degeneration: A MACUSTAR Study Report.},
journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research},
volume = {28},
number = {7},
pages = {1082-1090},
doi = {10.1016/j.jval.2025.04.2155},
pmid = {40294859},
issn = {1524-4733},
mesh = {Humans ; Female ; *Macular Degeneration/psychology/physiopathology/diagnosis ; Aged ; *Psychometrics ; Male ; *Quality of Life ; Reproducibility of Results ; *Vision Disorders/psychology/diagnosis/etiology ; Surveys and Questionnaires ; Middle Aged ; Aged, 80 and over ; United Kingdom ; Visual Acuity ; Feasibility Studies ; Germany ; },
abstract = {OBJECTIVES: The Vision Impairment in Low Luminance-Utility Index (VILL-UI) is a novel preference-weighted measure for use in patients with age-related macular degeneration (AMD). No evidence exists on its psychometric performance nor its performance in comparison with the generic preference-weighted measure, EQ-5D-5L, commonly used in economic evaluation. This study compares the psychometric performance of VILL-UI with EQ-5D-5L in patients with AMD.<br><br>METHODS: Assessments of feasibility, convergent/divergent validity, and known-group validity of VILL-UI and EQ-5D-5L are undertaken using MACUSTAR data at baseline, 12, 24, and 36 months. Analyses are undertaken separately using UK and German preference weights for both measures.<br><br>RESULTS: The sample with complete responses (n = 586) had mean age 71.9 years (standard deviation 6.9), 65.2% women, with predominantly intermediate AMD (87.2%). VILL-UI and EQ-5D-5L are feasible for completion, although VILL-UI has fewer usable responses due to its response options (baseline 89% vs 100%). EQ-5D-5L has high ceiling effects, with around one-third of participants reporting the best health state compared with under 8% for VILL-UI. Convergent validity between EQ-5D-5L and VILL-UI utilities and dimensions in which a relationship is expected is low, with divergent validity demonstrated where expected. VILL-UI detected statistically significant differences in known groups for visual acuity, visual function, and AMD stage across most time points, with little evidence of known-group validity for EQ-5D-5L.<br><br>CONCLUSIONS: VILL-UI is appropriate for use in future AMD studies to inform economic evaluation. VILL-UI has superior performance to EQ-5D-5L for known-group validity and has fewer ceiling effects but has fewer usable responses.},
}
@article {pmid40294585,
year = {2025},
author = {Basu, B and Mallick, S and Dhauria, S and Nagime, PV and Singh, S},
title = {Native/modified dextran-based nanogel in delivering drug and management of ocular complications: a review.},
journal = {Zeitschrift fur Naturforschung. C, Journal of biosciences},
volume = {},
number = {},
pages = {},
pmid = {40294585},
issn = {1865-7125},
abstract = {Ocular nanogels have emerged as a promising therapeutic approach, and nanotechnology has speed up the growth of the pharmaceutical and medical technology sectors. The physiological and anatomical barriers of the eye limit the use of traditional ocular preparations, which leads to low drug bioavailability and a brief retention period. This presents a serious problem for patients, doctors, and chemists. Nevertheless, nanogels can encapsulate medications within three-dimensional crosslinked polymeric networks and provide controlled and prolonged drug delivery by using particular structural layouts and unique preparation techniques, improving therapeutic efficacy and patient compliance. Dextran and its variants, a naturally occurring polysaccharide, have drawn a lot of interest in developing delivery systems for use in pharmaceutical and medical applications. Many dextran-based delivery systems with customized geometries and features have been fabricated recently, such as hydrogels, nanogels, magnetic nanoparticles, nanoemulsions, self-assembled micelles and nanoparticles, and microparticles. The review presents advancement and therapeutic potential of dextran-based nanogels for the treatment of various eye conditions, such as cataract, conjunctivitis, glaucoma, dry eye syndrome, age-related macular degeneration, and corneal ulcers. Moreover, the process for development and assessing these nanomedicines, emphasizing their safety and effectiveness as established by preclinical, toxicological, clinical assessments, and patent updates, has been elaborated.},
}
@article {pmid40294492,
year = {2025},
author = {Sabbah, HN and Alder, NN and Sparagna, GC and Bruce, JE and Stauffer, BL and Chao, LH and Pitceathly, RDS and Maack, C and Marcinek, DJ},
title = {Contemporary insights into elamipretide's mitochondrial mechanism of action and therapeutic effects.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {187},
number = {},
pages = {118056},
pmid = {40294492},
issn = {1950-6007},
support = {R35 GM142553/GM/NIGMS NIH HHS/United States ; R01 HL144778/HL/NHLBI NIH HHS/United States ; R01 HL165729/HL/NHLBI NIH HHS/United States ; R01 AG065879/AG/NIA NIH HHS/United States ; P01 AG001751/AG/NIA NIH HHS/United States ; R01 AG078279/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Animals ; *Mitochondria/drug effects/metabolism ; *Oligopeptides/pharmacology/therapeutic use ; Cardiolipins/metabolism ; Energy Metabolism/drug effects ; Mitochondrial Membranes/drug effects/metabolism ; },
abstract = {Mitochondria are cellular hubs integral for metabolism, signaling, and survival. Mitochondrial dysfunction is centrally involved in the aging process and an expansive array of disease states. Elamipretide is a novel mitochondria-targeting peptide that is under investigation for treating several disorders related to mitochondrial dysfunction. This review summarizes recent data that expand our understanding of the mechanism of action (MOA) of elamipretide. Elamipretide is a potential first-in-class therapeutic that targets the inner mitochondrial membrane. Despite initial descriptions of elamipretide's MOA involving reactive oxygen species scavenging, the last ten years have provided a significant expansion of how this peptide influences mitochondrial bioenergetics. The cardiolipin binding properties of elamipretide have been corroborated by different investigative teams with new findings about the consequences of elamipretide-cardiolipin interactions. In particular, new studies have shown elamipretide-mediated modulation of mitochondrial membrane electrostatic potentials and assembly of cardiolipin-dependent proteins that are centrally involved in mitochondrial physiology. These effects contribute to elamipretide's ability to improve mitochondrial function, structure, and bioenergetics. In animal studies, elamipretide-mediated amelioration of organ dysfunction has been observed in models of cardiac and skeletal muscle myopathies as well as ocular pathologies. A number of clinical trials with elamipretide have been recently completed, and a summary of the results focusing on Barth syndrome, primary mitochondrial myopathy, and age-related macular degeneration, is also provided herein. Elamipretide continues to show promise as a potential therapy for mitochondrial disorders. New basic science advances have improved understanding of elamipretide's MOA, enabling a better understanding of the molecular consequences of elamipretide-cardiolipin interactions.},
}
@article {pmid40293961,
year = {2025},
author = {Maniglia, M and Jayakumar, S and Demirayak, P and Maxwell, E and Anand, D and Cortez, J and Vice, JE and Visscher, KM and Seitz, AR},
title = {A Gaze-Contingent Display Framework for Perceptual Learning Research with Simulated Central Vision Loss.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {218},
pages = {},
doi = {10.3791/67596},
pmid = {40293961},
issn = {1940-087X},
mesh = {Humans ; *Macular Degeneration/physiopathology/rehabilitation ; Eye Movements/physiology ; *Learning/physiology ; Fixation, Ocular/physiology ; *Eye-Tracking Technology ; *Visual Perception/physiology ; },
abstract = {Macular degeneration (MD) is one of the leading causes of vision impairment in the Western world. Patients with MD tend to develop spontaneous eye movement strategies to compensate for their vision loss, including adopting a preferred retinal locus, or PRL, a spared peripheral region that they use more frequently to replace the damaged fovea. However, not all patients are successful in developing a PRL, and even when they do, it might take them months. Currently, no gold standard rehabilitative therapy exists, and MD research is further hindered by issues of recruitment, compliance, and comorbidity. To help address these issues, a growing body of research has used eye tracking-guided, gaze-contingent displays in a simulated central vision loss paradigm in individuals with intact vision. While simulated vision loss is qualitatively different than pathological central vision loss, our framework provides for a highly controlled model through which to study compensatory eye movements and test possible rehabilitation interventions in low vision. By developing a comprehensive framework, rather than relying on isolated and disconnected tasks, we create a cohesive environment where we can test larger-scale hypotheses, allowing us to examine interactions between tasks, assess training effects across multiple measures, and establish a consistent methodology for future research. Furthermore, participants in simulated central vision loss studies show similarities in their oculomotor compensatory behaviors compared to patients with MD. Here, we present a framework for conducting gaze-contingent studies related to simulated central vision loss. We emphasize the utilization of the framework to test behavioral and oculomotor performance of healthy individuals on a wide range of perceptual tasks encompassing different levels of visual processing. We also discuss how this framework can be adapted for training MD patients.},
}
@article {pmid40293479,
year = {2025},
author = {Quesada, E and Rojas, S and Campos, X and Wu, L},
title = {Gene therapy in neovascular age related macular degeneration: an update.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {8},
pages = {2135-2148},
pmid = {40293479},
issn = {1435-702X},
mesh = {Humans ; *Genetic Therapy/methods ; *Wet Macular Degeneration/therapy/genetics ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Neovascular age-related macular degeneration (NV-AMD) is a leading cause of preventable blindness in the elderly. Intravitreal injections of anti-VEGF agents are currently the treatment of choice for NV-AMD. However this treatment is burdensome and fosters non-compliance which leads to inferior visual outcomes. Gene therapy has emerged as a promising therapeutic option for NV-AMD that may improve these outcomes. Potential risks of gene therapy include a potential immune response that may be elicited by the vector, accidental activation of oncogenes or inactivation of tumor suppresor genes leading to malignant transformation via insertational mutagenesis and integration of the viral DNA inserts into the host's DNA. The main strategy of current gene therapy for NV-AMD has focused on delivering transgenes that express anti-angiogenic proteins that directly or indirectly inhibit the VEGF pathway. Ixoberogene soroparvovec, RGX-314 and 4D-150 are the leading NV-AMD genetic treatment programs. Pre-clinical models suggest that genome surgery with clustered regularly interspaced short palindromic repeats (CRISPR) may be another option in the future.},
}
@article {pmid40293407,
year = {2025},
author = {Cox, K and Shi, G and Read, N and Patel, MT and Ou, K and Liu, Z and Wu, J and Cendanawati, S and Le Brun Powell, J and Oppenheimer, PG and Hill, LJ and Nicholson, LB and Dick, AD and Liu, J},
title = {Age-Associated Decline in Autophagy Pathways in the Retinal Pigment Epithelium and Protective Effects of Topical Trehalose in Light-Induced Outer Retinal Degeneration in Mice.},
journal = {Aging cell},
volume = {24},
number = {7},
pages = {e70081},
pmid = {40293407},
issn = {1474-9726},
support = {SAC052//Sight Research UK/ ; 21-RG-1//Macular Society/ ; 2425-SC-01//Macular Society/ ; },
mesh = {Animals ; *Trehalose/pharmacology/administration &amp; dosage/therapeutic use ; *Autophagy/drug effects/radiation effects ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism/radiation effects ; Mice ; Humans ; *Light/adverse effects ; *Retinal Degeneration/pathology/drug therapy/etiology/metabolism ; *Aging/pathology/drug effects ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Administration, Topical ; *Macular Degeneration/pathology/drug therapy ; },
abstract = {Age is a primary risk factor for chronic conditions, including age-related macular degeneration (AMD). Impairments in autophagy processes are implicated in AMD progression, but the extent of autophagy's contribution and its therapeutic potential remain ambiguous. This study investigated age-associated transcriptomic changes in autophagy pathways in the retinal pigment epithelium (RPE) and evaluated the protective effects of topical trehalose, an autophagy-enhancing small molecule, against light-induced outer retinal degeneration in mice. Transcriptomic analysis of human RPE/choroid and mouse RPE revealed consistent downregulation of autophagy pathways with age, alongside variable changes as AMD severity progressed. Given the age- and AMD-associated perturbation of autophagy pathways, we examined trehalose treatment in vitro, which enhanced autophagic flux and restored mitochondrial respiratory function in primary murine RPE cells exposed to oxidative stress. In vivo, topical trehalose improved autophagy-lysosome activity in mouse RPE, as demonstrated by elevated LC3B turnover and SQSTM1/p62 degradation. Furthermore, trehalose eyedrops protected mice from light-induced damage to the RPE and photoreceptors, preserving outer nuclear layer thickness, RPE morphology, and junctional F-actin organization. Taken together, the data support that age-related decline and severe dysregulation in autophagy contributed to AMD progression. By restoring autophagic flux, topical trehalose demonstrates therapeutic potential to address early autophagy-related pathological changes in AMD.},
}
@article {pmid40292456,
year = {2025},
author = {Marques-Couto, P and Coelho-Costa, I and Ferreira-da-Silva, R and Andrade, JP and Carneiro, &#xc2;},
title = {Mediterranean Diet on Development and Progression of Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Observational Studies.},
journal = {Nutrients},
volume = {17},
number = {6},
pages = {},
pmid = {40292456},
issn = {2072-6643},
mesh = {Humans ; *Diet, Mediterranean ; *Macular Degeneration/prevention &amp; control ; Disease Progression ; Observational Studies as Topic ; Aged ; Male ; Female ; Risk Factors ; Middle Aged ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of vision impairment. A Mediterranean diet (MD) has been suggested to provide protective effects against AMD development and progression due to its antioxidant and anti-inflammatory properties. However, inconsistencies in findings across observational studies have been reported. This systematic review and meta-analysis aim to synthesize the existing evidence on the relationship between adherence to the MD and AMD development or progression.<br><br>METHODS: A systematic search was conducted using MEDLINE (via PubMed), Web of Science, and SCOPUS, following PRISMA guidelines. Observational studies assessing MD adherence in relation to AMD risk or progression were included. Meta-analyses were performed separately for each study design using odds ratios (ORs) for cross-sectional and case-control studies and hazard ratios (HRs) for prospective cohort studies. Heterogeneity was assessed using the I[2] statistic, and publication bias was evaluated via funnel plots.<br><br>RESULTS: Eight studies were included: two cross-sectional, three case-control, and three prospective cohort studies. The meta-analysis of cross-sectional studies (pooled OR = 0.96; 95% CI: 0.83-1.11; p = 0.6243; I[2] = 0%) found no significant association between MD adherence and AMD. However, the weight distribution was highly imbalanced, limiting interpretability. Meta-analyses of case-control and prospective cohort studies demonstrated a significant protective effect of MD adherence: case-control studies showed a 34% reduction in the odds of AMD progression (OR = 0.66; 95% CI: 0.54-0.81; p < 0.0001; I[2] = 41.5%), while prospective cohort studies indicated a 23% reduced risk of AMD progression (HR = 0.77; 95% CI: 0.67-0.88; p < 0.0001; I[2] = 0%).<br><br>CONCLUSIONS: This systematic review and meta-analysis suggest an inverse association between adherence to the MD and AMD progression, particularly in case-control and prospective cohort studies. Despite the small number of included studies, these findings highlight the potential role of diet in AMD management. Future research should focus on larger, well-controlled prospective studies with standardized dietary assessments.<br><br>KEY POINTS: 1. Higher adherence to the MD is associated with a reduced risk of AMD progression, with meta-analyses of case-control and prospective cohort studies showing 34% lower odds (OR = 0.66) and 23% reduced risk (HR = 0.77) of disease progression, respectively. 2. No significant association was found in cross-sectional studies (OR = 0.96; 95% CI: 0.83-1.11), likely due to methodological limitations and the challenge of establishing a temporal relationship between diet and AMD progression. 3. Despite the limited number of studies, findings suggest a potential role of diet in AMD management. Future research should prioritize larger, well-controlled prospective studies with standardized dietary assessments.},
}
@article {pmid40291395,
year = {2025},
author = {Zhang, KR and Nair, RM and Chen, Y and Jin, F and Dunaief, J and VanderBeek, BL},
title = {Association of Age-Related Macular Degeneration with Cholelithiasis.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100771},
pmid = {40291395},
issn = {2666-9145},
abstract = {PURPOSE: Dysregulated lipid metabolism likely contributes to the pathogenesis of age-related macular degeneration (AMD). There is an overlap in risk factors between AMD and diseases of lipid metabolism, such as cholelithiasis, suggesting that an association between these diseases could provide insight into AMD pathogenesis. This study sought to determine if there is an association between cholelithiasis and AMD.<br><br>DESIGN: A cohort study was conducted using patients in the Optum deidentified Clinformatics Data Mart database from January 1, 2000, to June 30,&#xa0;2022.<br><br>PARTICIPANTS: Patients over the age of 55 with &#x2265;2&#xa0;years of data and no prior history of AMD were included. The exposed cohort included patients who had a history of cholelithiasis, cholecystitis, or cholecystectomy. The control cohort included patients with gastroesophageal reflux disease (GERD), matched for age &#xb1;3 years, sex, race, and year of index date.<br><br>METHODS: Propensity scores were created using multivariable logistic regression and applied to inverse probability of treatment weighting (IPTW). Cox proportional hazard regression modeling with IPTW was used to compare progression to AMD in each cohort.<br><br>MAIN OUTCOME MEASURES: Progression to AMD for patients with cholelithiasis, cholecystitis, or a history of cholecystectomy.<br><br>RESULTS: A total of 332&#xa0;536 patients with cholelithiasis and 776&#xa0;591 matched GERD controls were analyzed. After IPTW, the mean age (&#xb1;standard deviation) was 66.6&#xa0;&#xb1;&#xa0;9.4 years in the cholelithiasis cohort and 67.5 (&#xb1;10.3) years in the GERD cohort. Women comprised 58% of the cholelithiasis cohort and 57% of the GERD cohort. In the cholelithiasis cohort, 3511.7 (1.14%) were diagnosed with AMD, compared with 23&#xa0;367.1 (2.92%) in the GERD cohort and corresponding to a significantly decreased hazard of AMD (adjusted hazard ratio [aHR]&#xa0;=&#xa0;0.72, 95% confidence interval [CI]: 0.69-0.75, P&#xa0;<&#xa0;0.0001). In the subanalysis, before IPTW weighting, AMD developed in 3809 of 275&#xa0;897 (1.4%) patients with only cholelithiasis (aHR&#xa0;=&#xa0;0.76, 95% CI: 0.73-0.80, P&#xa0;<&#xa0;0.0001), 335 of 47&#xa0;166 (0.71%) patients with cholecystitis (aHR&#xa0;=&#xa0;0.54, 95% CI: 0.47-0.61, P&#xa0;<&#xa0;0.0001), and 114 of 9473 (1.20%) patients who underwent cholecystectomy (aHR&#xa0;=&#xa0;0.50, 95% CI: 0.41-0.63, P&#xa0;<&#xa0;0.0001).<br><br>CONCLUSIONS: Cholelithiasis was associated with a 28% hazard reduction in AMD. More severe gallbladder disease conferred greater protection.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40290884,
year = {2025},
author = {Zuo, J and Pan, Y and Wang, Y and Wang, W and Zhang, H and Zhang, S and Wu, Y and Chen, J and Yao, Q},
title = {ROS-responsive drug delivery system with enhanced anti-angiogenic and anti-inflammatory properties for neovascular age-related macular degeneration therapy.},
journal = {Materials today. Bio},
volume = {32},
number = {},
pages = {101757},
pmid = {40290884},
issn = {2590-0064},
abstract = {Neovascular age-related macular degeneration (nAMD) has become the leading cause of vision loss in people over 60 years old. Anti-vascular endothelial growth factor (anti-VEGF), the current first-line drug for the treatment of nAMD, suffers from poor patient compliance and fundus fibrosis scar formation. In addition to VEGF, oxidative stress and inflammation also play key roles in the pathological process of choroidal neovascularization (CNV). Therefore, combinational therapeutics with anti-angiogenic, reactive oxygen species (ROS)-scavenging and anti-inflammatory functions will broaden therapeutic effects and reduce side effects. The Yes-associated protein-1 (YAP) has proven to inhibit angiogenesis, inflammation, and subretinal fibrosis in CNV. Herein, verteporfin (VP), the inhibitor of YAP, was encapsulated into a polydopamine modified mesoporous silica nanoparticle (PMSN-VP NPs) and then conjugated with PLGA-PEG-PBA decorated cerium oxide nanoparticles (PPCeO2 NPs) to develop an integrated nano-drug delivery system. The PMSN-VP@PPCeO2 NPs exhibited ROS-responsive degradation and VP release behaviors, and our in vitro data revealed that the PMSN-VP@PPCeO2 NPs downregulated angiogenic-related and fibrosis-related gene expressions in human umbilical vein endothelial cells (HUVECs) and further showed excellent anti-oxidative and anti-inflammatory capacities in BV2 cells. More importantly, the PMSN-VP@PPCeO2 NPs significantly suppressed vascular leakage and macrophage infiltration in the laser-induced CNV lesions of mice. Overall, our findings demonstrated that the PMSN-VP@PPCeO2 NPs provided an effective therapeutic strategy for nAMD.},
}
@article {pmid40288597,
year = {2025},
author = {Kailani, Z and Mihalache, A and Popovic, MM and Kertes, PJ and Muni, RH},
title = {Ocular Adverse Events Associated with Pegcetacoplan and Avacincaptad Pegol for Geographic Atrophy: A Population-Based Pharmacovigilance Study.},
journal = {American journal of ophthalmology},
volume = {276},
number = {},
pages = {252-260},
doi = {10.1016/j.ajo.2025.04.022},
pmid = {40288597},
issn = {1879-1891},
mesh = {Humans ; Retrospective Studies ; *Pharmacovigilance ; Male ; Female ; Aged ; *Geographic Atrophy/drug therapy/diagnosis ; Adverse Drug Reaction Reporting Systems/statistics &amp; numerical data ; United States/epidemiology ; Aged, 80 and over ; Intravitreal Injections ; Middle Aged ; *Certolizumab Pegol/adverse effects ; United States Food and Drug Administration ; },
abstract = {OBJECTIVE: To evaluate the postmarketing ocular adverse events (AEs) reported for avacincaptad pegol and pegcetacoplan, the only Food and Drug Administration (FDA)-approved treatments for geographic atrophy (GA).<br><br>DESIGN: Retrospective pharmacovigilance analysis.<br><br>SUBJECTS: Ocular AE reports in the FDA Adverse Event Reporting System (FAERS) in which pegcetacoplan or avacincaptad pegol was identified as the primary suspect drug were analyzed.<br><br>METHODS: Using the OpenVigil 2.1 data mining software, we conducted a retrospective pharmacovigilance analysis of the FAERS database from inception to December 2024. We conducted disproportionality analyses to assess reporting odds ratios (RORs) for specific drug-AE combinations compared with all other drugs in the database.<br><br>MAIN OUTCOME MEASURES: Ocular AEs were evaluated.<br><br>RESULTS: A total of 752 and 80 patients with AEs secondary to pegcetacoplan and avacincaptad pegol, respectively, were identified. Ocular AEs disproportionately overreported for pegcetacoplan included anterior segment (iris) hemorrhage (ROR 1767, 95% CI 538-5803), iris neovascularization (ROR 1248, 95% CI 502-3099), choroidal neovascularization (ROR 1328, 95% CI 956-1845), intraocular injection complication (ROR 2552, 95% CI 1607-4053), hemorrhagic occlusive retinal vasculitis (ROR 4606, 95% CI 2000-10,611), retinal occlusive vasculitis (ROR 2352, 95% CI 1313-4212), and bacterial endophthalmitis (ROR 1260, 95% CI 613-2589). Ocular AEs disproportionately overreported for avacincaptad pegol included choroidal neovascularization (ROR 1169, 95% CI 426-3205), vitritis (ROR 782, 95% CI 316-1936), dry age-related macular degeneration (ROR 684, 95% CI 316-1936), and cystoid macular edema (ROR 445, 95% CI 140-1412).<br><br>CONCLUSIONS: Current prescribing patterns indicate that a broader spectrum of ocular AEs were reported for pegcetacoplan than avacincaptad pegol. These findings aim to enhance clinicians' understanding of the safety profiles of these agents, enabling informed patient care and heightened vigilance of these novel GA treatments.},
}
@article {pmid40287896,
year = {2025},
author = {Nissen, AHK and Torp, TL and Vergmann, AS},
title = {Clinical Outcomes of Treatment of Geographic Atrophy: A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {6},
pages = {1173-1181},
pmid = {40287896},
issn = {2193-8245},
abstract = {RATIONALE: In 2023, the U.S. Food and Drug Administration approved pegcetacoplan (SYFOVRE) as the first therapeutic option for geographic atrophy (GA), a previously untreatable condition associated with age-related macular degeneration. Following this, avacincaptad pegol (Izervay) was also approved for GA treatment, further expanding therapeutic options.<br><br>OBJECTIVES: This article aims to give an overview of the clinical outcomes of GA treatment and to discuss which patient groups may benefit most from these therapies.<br><br>METHODS: A review of the literature was conducted using the databases PubMed, Cochrane Library, and ClinicalTrials.gov. The search yielded six relevant studies.<br><br>CONCLUSIONS: The management of geographic atrophy has advanced with therapies like pegcetacoplan and avacincaptad pegol showing clear benefits in slowing lesion growth. However, safety concerns, such as neovascular complications, persist. Photobiomodulation and dietary supplementation provide alternative options with modest benefits, particularly in the early stages. Larger studies are needed to confirm long-term safety, efficacy, and optimal treatment strategies.},
}
@article {pmid40285355,
year = {2025},
author = {Chew, LA and Grigsby, D and Hester, CG and Amason, J and McPherson, WK and Flynn, EJ and Visel, M and Starr, CR and Flannery, JG and Lewis, TR and Bowes Rickman, C},
title = {Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {33},
number = {8},
pages = {3746-3756},
pmid = {40285355},
issn = {1525-0024},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Genetic Therapy/methods ; *Complement Factor H/genetics ; Mice ; Humans ; Dependovirus/genetics ; *Complement C3/genetics/metabolism/immunology ; Disease Models, Animal ; Genetic Vectors/genetics/administration &amp; dosage ; *Glomerulonephritis/therapy/genetics/pathology/metabolism ; Mice, Knockout ; Complement Pathway, Alternative ; Macular Degeneration/therapy/genetics ; },
abstract = {There are no effective therapies for patients with dry age-related macular degeneration (AMD) or C3 glomerulonephritis (C3G). Unfortunately, past efforts to treat C3G using exogenous human complement factor H (CFH) found limited success due to immune rejection of a foreign protein response. AMD research has also faced myriad challenges, including the absence of an ideal therapeutic target and difficulties with treatment delivery in certain preclinical models. In pursuit of an AMD therapy to overcome these obstacles, we ultimately capitalized on parallels in complement dysregulation between AMD and C3G. Here, we investigate the potential for CFH supplementation as a strategy to rescue C3G. Our findings demonstrate restored inhibition of complement's alternative pathway and long-term reversal of disease without immune rejection using adeno-associated virus (AAV)-mediated delivery of truncated CFH (tCFH) in a Cfh[-/-] mouse model of C3G. We tested three different tCFH vectors and found significant differences in their relative transduction efficiency and therapeutic efficacy. These discoveries motivate the development of AAV-mediated tCFH replacement therapy for patients with C3G while simultaneously demonstrating proof of concept for AAV-mediated tCFH gene augmentation therapy for patients with AMD.},
}
@article {pmid40283989,
year = {2025},
author = {Nowak, I and Kubina, R and Strzałka-Mrozik, B},
title = {Therapeutic Potential of Hexahydrocurcumin in the Regeneration and Protection of the Retinal Pigment Epithelium.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {4},
pages = {},
pmid = {40283989},
issn = {1424-8247},
support = {BNW-1-039/N/4/F//Medical University of Silesia/ ; },
abstract = {Hexahydrocurcumin (HHC), the primary metabolite of curcumin, shows promising therapeutic potential due to its antioxidant and anti-inflammatory properties. The retinal pigment epithelium (RPE) plays a crucial role in maintaining retinal homeostasis; however, its dysfunction-linked to oxidative stress and chronic inflammation-contributes to the progression of degenerative diseases such as age-related macular degeneration (AMD). This review highlights the therapeutic potential of HHC in protecting and regenerating RPE cells. It explores the effects of oxidative stress on the RPE, the mechanisms underlying its damage, and the involvement of reactive oxygen species (ROS) and inflammatory mediators. HHC has demonstrated the ability to modulate these pathways by activating nuclear factor erythroid 2-related factor 2 (NRF2), enhancing antioxidant defenses, and inhibiting pro-inflammatory cytokine production. Preclinical studies suggest that HHC mitigates vascular remodeling and endothelial dysfunction by reducing the expression of transforming growth factor β (TGF-β1) and matrix metalloproteinase-9 (MMP-9). Moreover, HHC improves nitric oxide bioavailability and promotes nitric oxide synthase expression, thereby counteracting oxidative stress-induced vascular damage. Emerging evidence indicates that HHC may be a promising candidate for the treatment of retinal degenerative diseases, particularly those associated with oxidative stress and inflammation. However, further studies, including clinical trials, are essential to confirm its efficacy and elucidate the precise mechanisms underlying HHC's protective effects on RPE cells.},
}
@article {pmid40283970,
year = {2025},
author = {Liu, C and Liu, X and Duan, J},
title = {Artemisinin and Its Derivatives: Promising Therapeutic Agents for Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {4},
pages = {},
pmid = {40283970},
issn = {1424-8247},
support = {[82074335], [82474394]//the National Natural Science Foundation of China/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in older adults. Its pathogenesis involves multiple factors, including aging, environmental influences, genetic predisposition, oxidative stress, metabolic dysfunction, and immune dysregulation. Currently, AMD treatment focuses primarily on wet AMD, managed through repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) therapies. While anti-VEGF agents represent a major breakthrough in wet AMD care, repeated injections may lead to incomplete responses or resistance in some patients, and carry a risk of progressive fibrosis. Artemisinin (ART) and its derivatives, originally developed as antimalarial drugs, exhibit a broad spectrum of pleiotropic activities beyond their established use, including anti-inflammatory, anti-angiogenic, antioxidant, anti-fibrotic, mitochondrial regulatory, lipid metabolic, and immunosuppressive effects. These properties position ART as a promising therapeutic candidate for AMD. A growing interest in ART-based therapies for AMD has emerged in recent years, with numerous studies demonstrating their potential benefits. However, no comprehensive review has systematically summarized the specific roles of ART and its derivatives in AMD pathogenesis and treatment. This paper aims to fill the knowledge gap by synthesizing the therapeutic efficacy and molecular mechanisms of ART and its derivatives in AMD, thereby providing a foundation for future investigations.},
}
@article {pmid40283193,
year = {2025},
author = {Timofte Zorila, MM and Vitiello, L and Lixi, F and Coppola, A and Cukurova, F and Pellegrino, A and Giannaccare, G},
title = {Photic Retinopathy: Diagnosis and Management of This Phototoxic Maculopathy.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
pmid = {40283193},
issn = {2075-1729},
abstract = {Photic retinopathy is an uncommon clinical entity characterized by retinal damage brought on by excessive exposure to light without protection. It encompasses several distinct clinical categories, including solar maculopathy, handheld laser maculopathy, arc welding maculopathy, and iatrogenic macular degeneration. These clinical entities result from exposure to diverse light sources, such as solar radiation, laser pointers, welding arcs, and operating microscopes during ophthalmic procedures. Patients typically present with bilateral but asymmetric symptoms, including reduced visual acuity, central or paracentral scotomas, photophobia, metamorphopsia, and headaches. After exposure, most people can recover on their own in a matter of weeks to six months without the need for special care. However, thanks to their anti-inflammatory properties, several clinical cases reporting the use of steroids for acute photic retinopathy have been documented in the scientific literature, together with the use of antioxidants. The purpose of this review is to provide an update on this phototoxic maculopathy, describing its different clinical entities, diagnosis, and treatment options, and also focusing on the role of optical coherence tomography for its management.},
}
@article {pmid40281694,
year = {2025},
author = {Racioppo, P and Alhasany, A and Pham, NV and Wang, Z and Corradetti, G and Mikaelian, G and Paulus, YM and Sadda, SR and Hu, Z},
title = {Automated Foveal Avascular Zone Segmentation in Optical Coherence Tomography Angiography Across Multiple Eye Diseases Using Knowledge Distillation.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {4},
pages = {},
pmid = {40281694},
issn = {2306-5354},
support = {5R21EY030619-22A1/NH/NIH HHS/United States ; },
abstract = {Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique used to visualize retinal blood flow and identify changes in vascular density and enlargement or distortion of the foveal avascular zone (FAZ), which are indicators of various eye diseases. Although several automated FAZ detection and segmentation algorithms have been developed for use with OCTA, their performance can vary significantly due to differences in data accessibility of OCTA in different retinal pathologies, and differences in image quality in different subjects and/or different OCTA devices. For example, data from subjects with direct macular damage, such as in age-related macular degeneration (AMD), are more readily available in eye clinics, while data on macular damage due to systemic diseases like Alzheimer's disease are often less accessible; data from healthy subjects may have better OCTA quality than subjects with ophthalmic pathologies. Typically, segmentation algorithms make use of convolutional neural networks and, more recently, vision transformers, which make use of both long-range context and fine-grained detail. However, transformers are known to be data-hungry, and may overfit small datasets, such as those common for FAZ segmentation in OCTA, to which there is limited access in clinical practice. To improve model generalization in low-data or imbalanced settings, we propose a multi-condition transformer-based architecture that uses four teacher encoders to distill knowledge into a shared base model, enabling the transfer of learned features across multiple datasets. These include intra-modality distillation using OCTA datasets from four ocular conditions: healthy aging eyes, Alzheimer's disease, AMD, and diabetic retinopathy; and inter-modality distillation incorporating color fundus photographs of subjects undergoing laser photocoagulation therapy. Our multi-condition model achieved a mean Dice Index of 83.8% with pretraining, outperforming single-condition models (mean of 83.1%) across all conditions. Pretraining on color fundus photocoagulation images improved the average Dice Index by a small margin on all conditions except AMD (1.1% on single-condition models, and 0.1% on multi-condition models). Our architecture demonstrates potential for broader applications in detecting and analyzing ophthalmic and systemic diseases across diverse imaging datasets and settings.},
}
@article {pmid40281120,
year = {2025},
author = {Mu, T and He, HL and Chen, XY and Fang, YX and Xu, J and Jin, ZB},
title = {Axial length as a predictor of myopic macular degeneration: a meta-analysis and clinical study.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {2073-2082},
pmid = {40281120},
issn = {1476-5454},
mesh = {Humans ; *Macular Degeneration/diagnosis/physiopathology/etiology ; *Myopia, Degenerative/diagnosis/physiopathology/complications ; *Axial Length, Eye/pathology ; Visual Acuity/physiology ; Female ; Male ; Middle Aged ; },
abstract = {PURPOSE: This study aims to investigate the relationship between axial length (AL) and the severity of myopic macular degeneration (MMD).<br><br>METHODS: We conducted a comprehensive search of PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) databases from their inception until October 1, 2023, to identify population-based or hospital-based studies reporting AL across different grades of MMD. Only studies employing the International Photographic Classification and Grading System for Myopic Maculopathy (META-PM) were included. A meta-analysis was performed to assess the association between AL and MMD severity. To further validate our findings, we analyzed data from 395 eyes of 206 participants at Beijing Tongren Hospital, Capital Medical University.<br><br>RESULTS: The meta-analysis included 20 high-quality studies from seven countries, with 33822 patients studied. Information, including the study name, year of publication, country, sample size, basic demographic characteristics of the participants, AL of different grades of MMD, best corrected visual acuity (BCVA), and spherical equivalent (SE), was extracted. The meta-analysis revealed a significant overall increase in AL as MMD progressed from category C0 to C4 (P&#x2009;<&#x2009;0.0001). AL exhibited a consistent increasing trend from categories C0 to C3; however, this trend appeared to level off between categories C3 and C4, with no further increase observed. This trend was confirmed by the distribution of our new dataset. A higher prevalence of MMD was significantly associated with longer AL (per 1&#x2009;mm increase: OR, 1.90; 95% CI, 1.75-2.07; P&#x2009;<&#x2009;0.001), older age (per 1-year increase: OR, 1.04; 95% CI, 1.02-1.05; P&#x2009;<&#x2009;0.001), and female gender (OR, 1.89; 95% CI, 1.24-2.89; P&#x2009;<&#x2009;0.01). Compared with C0, each 1&#x2009;mm increase in AL was associated with an increasing likelihood of MMD progression, with ORs of 2.8 for C1, 3.6 for C2, 5.2 for C3, and 5.7 for C4. The increase in OR was more pronounced in later stages (C2-C3 and C3-C4) than in earlier transitions (C0-C1 and C1-C2). Similarly, the ORs for age increased significantly from C3 to C4, and the ORs for female gender increased progressively from C2 to C4.<br><br>CONCLUSIONS: The meta-analysis and new clinical study indicate a clear trend of increasing AL with advancing MMD severity from C0 to C4. However, the relationship between AL and MMD progression from C3 to C4 warrants further investigation. Additionally, older age and female gender are identified as risk factors for MMD progression.},
}
@article {pmid40280538,
year = {2025},
author = {Zaluski, J and Bassetto, M and Kiser, PD and Tochtrop, GP},
title = {Advances and therapeutic opportunities in visual cycle modulation.},
journal = {Progress in retinal and eye research},
volume = {106},
number = {},
pages = {101360},
pmid = {40280538},
issn = {1873-1635},
support = {I01 BX004939/BX/BLRD VA/United States ; IK6 BX006800/BX/BLRD VA/United States ; R01 EY034519/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Animals ; Retinoids/metabolism ; Photoreceptor Cells, Vertebrate/metabolism ; *Vision, Ocular/physiology ; *Retinaldehyde/metabolism ; },
abstract = {The visual cycle is a metabolic pathway that enables continuous vision by regenerating the 11-cis-retinal chromophore for photoreceptors opsins. Although integral to normal visual function, the flux of retinoids through this cycle can contribute to a range of retinal pathologies, including Stargardt disease, age-related macular degeneration, and diabetic retinopathy. In such conditions, intermediates and byproducts of the visual cycle, such as bisretinoid components of lipofuscin, can accumulate, concomitant with cellular damage and eventual photoreceptor loss. This has inspired efforts to modulate the visual cycle, aiming to slow or prevent the formation of these toxic intermediates and thus preserve retinal structure and function. Over the past two decades, multiple strategies to modulate the visual cycle have emerged. These include both intrinsic approaches, targeting key enzymes, retinoid-binding proteins, or receptors within the pigment epithelium or photoreceptors (e.g., RPE65, CRBP1, and rhodopsin inhibitors/antagonists) and extrinsic strategies that indirectly alter retinoid availability within the retina (e.g., RBP4 antagonists). Many of these agents have shown promise in animal models of visual cycle-associated retinal diseases, reducing pathological changes, and improving retinal survival. Several have advanced into clinical studies, although none are currently FDA-approved. Challenges remain in optimizing drug specificity and duration of action while minimizing side effects such as nyctalopia. In this review, we comprehensively examine current and emerging visual cycle modulators, discuss their medicinal chemistry, mechanisms of action, efficacy in preclinical and clinical studies, and highlight future opportunities for drug discovery aimed at safely and effectively preserving vision through modulation of this biochemical pathway.},
}
@article {pmid40280535,
year = {2025},
author = {Wu, Y and Zhao, J and Lu, X},
title = {Profiling the Ocular Landscape of sEVs miRNAs: Mechanisms and Applications.},
journal = {Experimental eye research},
volume = {256},
number = {},
pages = {110396},
doi = {10.1016/j.exer.2025.110396},
pmid = {40280535},
issn = {1096-0007},
mesh = {Humans ; *MicroRNAs/genetics ; *Eye Diseases/genetics/therapy/metabolism ; Animals ; Biomarkers/metabolism ; },
abstract = {In this review, we comprehensively discuss the application of sEVs miRNAs in ophthalmic diseases by examining their basic characteristics and clinical application potential. Initially, we provide an overview of sEVs, including their definition, source, and functions, while particularly highlighting the importance of miRNAs contained in sEVs and its prospects in the treatment of ocular diseases. Subsequently, the structure and composition of sEVs as well as the biological functions of their encapsulated miRNAs, which expands the current knowledge about their roles in ophthalmic physiology and pathology. In addition, the functions of sEVs miRNAs in the growth of ocular tissues, ocular tissue homeostasis, and common eye diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy, are discussed. The application potential of sEVs miRNAs as diagnostic biomarkers and drug delivery systems for ophthalmic conditions and therapeutic value in diverse eye diseases are explored. Finally, the current challenges affecting research in this field are outlined to provide a basis that guide future utilization of sEVs miRNAs in ophthalmic disease research and clinical management of diverse ophthalmological conditions.},
}
@article {pmid40280279,
year = {2025},
author = {Wykoff, CC and Holz, FG and Chiang, A and Boyer, D and Dhoot, DS and Loewenstein, A and Mones, J and Heier, J and Abbey, AM and Singerman, LJ and Vajzovic, L and Lin, J and Li, C and Vilupuru, A and Baumal, CR and , },
title = {Pegcetacoplan Treatment for Geographic Atrophy in Age-Related Macular Degeneration Over 36 Months: Data From OAKS, DERBY, and GALE.},
journal = {American journal of ophthalmology},
volume = {276},
number = {},
pages = {350-364},
doi = {10.1016/j.ajo.2025.04.016},
pmid = {40280279},
issn = {1879-1891},
mesh = {Humans ; *Geographic Atrophy/drug therapy/diagnosis/physiopathology ; Prospective Studies ; Aged ; Male ; Intravitreal Injections ; *Visual Acuity/physiology ; Female ; Tomography, Optical Coherence ; Fluorescein Angiography ; Aged, 80 and over ; Follow-Up Studies ; Treatment Outcome ; *Macular Degeneration/drug therapy/diagnosis/complications ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors ; Time Factors ; Cross-Over Studies ; },
abstract = {PURPOSE: To report 12-month results from the GALE open-label extension study (NCT04770545), evaluating up to 36 months of intravitreal pegcetacoplan treatment for geographic atrophy (GA) in age-related macular degeneration (AMD).<br><br>DESIGN: GALE is a prospective open-label extension study following the 24-month, sham-controlled, phase 3 OAKS (NCT03525613) and DERBY (NCT03525600) studies of pegcetacoplan.<br><br>PARTICIPANTS: Patients with nonsubfoveal or subfoveal GA who completed OAKS, DERBY, or phase 1b APL2-103 (NCT03777332) studies.<br><br>METHODS: Pegcetacoplan was administered monthly (PM) or every other month (PEOM) to all study eyes in GALE. Eyes receiving pegcetacoplan in OAKS and DERBY continued the same regimen (PM-PM and PEOM-PEOM), while eyes observed with sham in OAKS and DERBY crossed over to receive pegcetacoplan at the same dosing interval in GALE (SM-PM and SEOM-PEOM). Safety and efficacy through the first 12 months of GALE were assessed, reflecting up to 36 months of continuous pegcetacoplan treatment.<br><br>MAIN OUTCOME MEASURE: Mean rate of change in GA area, total number of microperimetry scotomatous points, and adverse events.<br><br>RESULTS: Through the first 12 months of GALE, 92.0% (727/790) patient retention was observed. Across all eyes, including eyes with nonsubfoveal and subfoveal GA, pegcetacoplan reduced the mean rate of change in GA area up to 32% versus projected sham. Year after year, the reductions in the mean rate of change in GA area increased, with up to a 42% reduction observed in eyes with nonsubfoveal GA in the PM-PM group compared with projected sham in the first year of GALE. An 18% reduction in new scotomatous points (P = .0156) was observed with PM-PM at 36 months, highlighting a significant impact in a prespecified microperimetry analysis. Adverse events included 33 (4.5%) eyes with exudative AMD, 15 (1.9%) intraocular inflammation (classified as mild or moderate in severity), 1 (0.1%) ischemic optic neuropathy, and 1 (0.1%) infectious endophthalmitis. No events of vasculitis were reported.<br><br>CONCLUSION: Over 36 months, pegcetacoplan continued to reduce GA growth with increasing efficacy over time and reduced formation of new scotomatous points. The safety profile of pegcetacoplan in the first 12 months of GALE was consistent with the prior 24-month OAKS and DERBY studies.},
}
@article {pmid40280278,
year = {2025},
author = {Chiang, B and Chung, YG and Prausnitz, MR},
title = {Suprachoroidal Drug Delivery for VEGF Suppression in Wet AMD and Other Diseases With Choroidal Neovascularization.},
journal = {American journal of ophthalmology},
volume = {277},
number = {},
pages = {556-569},
doi = {10.1016/j.ajo.2025.04.020},
pmid = {40280278},
issn = {1879-1891},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Choroid/drug effects ; *Choroidal Neovascularization/drug therapy/etiology/diagnosis ; *Drug Delivery Systems/methods ; Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/complications/diagnosis ; },
abstract = {PURPOSE: Choroidal neovascularization caused by age-related macular degeneration, among other diseases, causes significant visual impairment. Intravitreal therapeutics inhibiting vascular endothelial growth factor (VEGF) signaling have shown excellent safety and efficacy in regressing choroidal neovascularization and improving vision. Current US Food and Drug Administration (FDA)-approved treatments deliver these drugs into the vitreous cavity, even though choroidal neovascularization originates from aberrant signaling in the choroid.<br><br>DESIGN: Systematic review.<br><br>METHODS: A literature search was conducted across PubMed and Google Scholar from inception up to December 31, 2024, focusing on studies investigating suprachoroidal delivery of anti-VEGF therapy. Randomized controlled trials, cohort studies, and case-control studies were included, whereas case reports and review articles were excluded.<br><br>RESULTS: A total of 15 peer-reviewed articles, 3 press releases, 6 conference abstracts and presentations, and 8 clinical trials were identified that were relevant to the topic of suprachoroidal delivery of anti-VEGF therapy.<br><br>CONCLUSIONS: The suprachoroidal space is a potential space between the sclera and the choroid, which has recently become a route of delivery in an FDA-approved treatment. Notably, suprachoroidal delivery results in higher choroidal drug concentrations than intravitreal delivery. Promising results thus far have been seen with suprachoroidal delivery of VEGF-targeting therapies in clinical and preclinical studies; however, future work is needed to more fully demonstrate safety and efficacy.},
}
@article {pmid40278361,
year = {2025},
author = {Sourirajan, K and Mendez, K and Lains, I and Tsougranis, G and Kang, H and Kozak, G and Bannerman, A and Bhat, R and Choi, H and Nigalye, A and Kim, IK and Vavvas, DG and Wu, DM and Liang, L and Miller, JB and Miller, JW and Lasky-Su, J and Husain, D},
title = {Plasma and Urine Metabolites Associated with Microperimetric Retinal Sensitivity in Age-Related Macular Degeneration.},
journal = {Metabolites},
volume = {15},
number = {4},
pages = {},
pmid = {40278361},
issn = {2218-1989},
support = {R01 EY030088/EY/NEI NIH HHS/United States ; R01 HL123915/HL/NHLBI NIH HHS/United States ; R01 HL141826/HL/NHLBI NIH HHS/United States ; R01EY030088//NIH/ NEI/ ; },
abstract = {BACKGROUND: Best-corrected visual acuity (BCVA) is the current gold standard of retinal function measurement but is not affected in early and intermediate forms of age-related macular degeneration (AMD). Increasing evidence suggests that microperimetry is a sensitive measure of visual function. This study sought to analyze the associations between plasma and urine metabolites and microperimetry in AMD.<br><br>METHODS: We included data on 363 eyes (95 controls, 268 AMD). Microperimetry was performed in patients with or without AMD using the Macular Integrity Assessment (MAIA) microperimetry system, employing a 37-point full-threshold protocol. Plasma and urine samples were analyzed via ultra-high-performance liquid chromatography-mass spectrometry. Multilevel mixed-effects linear models were used to assess associations between the metabolites and retinal sensitivity. Statistical significance was determined by considering the number of independent tests that accounted for 80% of the variance (ENT80).<br><br>RESULTS: We identified two plasma and seven urine metabolites, which were significantly associated with mean retinal sensitivity in AMD, and the key results include metabolites in the lysine metabolism pathway.<br><br>CONCLUSIONS: To our knowledge, we present the first assessment of the associations between plasma and urinary metabolites and retinal microperimetry sensitivity in AMD. This work can reveal more insight into the pathogenesis of AMD.},
}
@article {pmid40278325,
year = {2025},
author = {Boberg-Ans, S and Arnold-Vangsted, F and Scheel-Bech, AB and Boberg-Ans, LC and Arnold-Vangsted, A and Jakobsen, C and Stokbro, K and Subhi, Y},
title = {A Systematic Review and Meta-Analysis Association Between Periodontitis and Age-Related Macular Degeneration: Potential for Personalized Approach.},
journal = {Journal of personalized medicine},
volume = {15},
number = {4},
pages = {},
pmid = {40278325},
issn = {2075-4426},
abstract = {Background/Objectives: Periodontitis is a chronic inflammatory disease that leads to systemic low-grade inflammation. Systemic low-grade inflammation has been found in patients with age-related macular degeneration (AMD). In this systematic review and meta-analysis, we evaluated the association between periodontitis and AMD. Methods: We searched 11 scientific literature databases on 16th December 2024 for studies of a diagnosis of periodontitis and prevalent or incident AMD. Eligible studies underwent a qualitative review and meta-analysis of the association. Study selection, data extraction, and risk of bias within studies were made in duplicate by two authors and conferred with a senior author. Results: Seven studies eligible for review included in total 149,217 individuals. Across the seven studies, different study designs, diagnoses and definitions of periodontitis, and diagnosis and definitions of AMD were employed. Our meta-analysis showed an association between periodontitis and AMD with an odds ratio of 1.42 (95% CI: 1.12 to 1.78; p = 0.003). Conclusions: Periodontitis is significantly associated with AMD. Unlike genetic predisposition and high age, which are important risk factors of AMD that cannot be modified, periodontitis is a risk factor that can be treated and potentially eliminated, thus allowing for a personalized approach for risk elimination in AMD. Attention should be given to the dental health of patients at risk of AMD.},
}
@article {pmid40276124,
year = {2025},
author = {Saeed, A and Guymer, RH and Hadoux, X and Jannaud, M and Dang, D and Hodgson, LAB and Glover, EK and Gee, EE and van Wijngaarden, P and Wu, Z},
title = {Customized Evaluation of Progressive Visual Sensitivity Loss in Geographic Atrophy to Improve the Power of Clinical Trials.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100763},
pmid = {40276124},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the effectiveness of different approaches for customizing the selection of a subset of test locations on defect-mapping microperimetry (DMP) for improving the detection of progressive visual function decline in geographic atrophy (GA).<br><br>DESIGN: Prospective longitudinal study.<br><br>PARTICIPANTS: Sixty eyes from 53 participants with GA secondary to age-related macular degeneration.<br><br>METHODS: Participants underwent 3-monthly DMP testing twice at each visit for up to 24 months, where the extent of deep visual sensitivity losses on each test was determined through single presentations of 10-decibel stimuli at 208 locations within the central 8&#xb0; radius region. Seven outcome measures were derived, which included evaluating the proportion of locations missed (PLM; showing nonresponse to stimuli) on DMP in a subset of test locations based on their proximity to the GA margin, or to locations neighboring repeatably nonresponding points on 2 baseline tests (i.e., missed both tests at baseline). These outcome measures were compared by their coefficient of variation (CoV; reflecting performance for capturing longitudinal changes) and sample size estimates in a 2-arm trial seeking to detect a &#x2265;30% treatment effect. Changes in GA extent and best-corrected visual acuity (BCVA) were evaluated for comparison.<br><br>MAIN OUTCOME MEASURES: Coefficient of variation and sample size estimates.<br><br>RESULTS: Evaluating PLM at points immediately adjacent (<1&#xb0;) to repeatably nonresponding test locations at baseline (CoV&#xa0;= 47%) was the best performing outcome measure on DMP testing. This measure outperformed BCVA (CoV&#xa0;= 188%; P < 0.001) at detecting longitudinal changes and was comparable to evaluating GA extent (CoV&#xa0;= 58%; P&#xa0;= 0.097). Sample size requirements in a 24-month trial using this outcome measure on DMP testing were lower by 46% and 94% compared with evaluating GA extent and BCVA, respectively.<br><br>CONCLUSIONS: Customized evaluation of DMP functional testing results in regions adjacent to repeatably nonresponding locations at baseline improved the detection of longitudinal changes compared with the evaluation of all test locations. These findings show that it is possible to sensitively capture progressive visual function decline with this approach, supporting its use in future GA treatment trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40276027,
year = {2025},
author = {Josifova, T and Konieczka, K and Schötzau, A and Flammer, J},
title = {The effect of a specific vitamin supplement containing L-methylfolate (Ocufolin forte) in patients with neovascular age-related macular degeneration.},
journal = {Advances in ophthalmology practice and research},
volume = {5},
number = {2},
pages = {135-141},
pmid = {40276027},
issn = {2667-3762},
abstract = {BACKGROUND: Patients with nAMD often have pathologically elevated homocysteine (Hcy) and increased retinal venous pressure (RVP). We tested whether the administration of a specific vitamin preparation containing L-methylfolate (Ocufolin forte) as an addition to anti-VEGF therapy reduces these two risk factors and favorably influences the disease course.<br><br>METHODS: A total of 27 eyes/27 patients with intra- and subretinal fluid, Hcy above 12&#xa0;&#x200b;&#x3bc;mol/L, RVP of at least 8&#xa0;&#x200b;mm above the IOP, and an IOP between 10 and 20&#xa0;&#x200b;mmHg were included in this study. All eyes received three injections of 0.05&#xa0;&#x200b;ml aflibercept at one-month intervals as clinically indicated. Fifteen patients additionally received one capsule of Ocufolin forte per day (Ocufolin group, OG), and the other twelve patients served as a control group (control group, CG). The following factors were measured before therapy and four months later: blood Hcy, best-corrected visual acuity (BCVA), intra-ocular pressure (IOP), RVP, optical coherence tomography (OCT), and optical coherence tomography - angiography (OCTA).<br><br>RESULTS: Hcy decreased on average by 5.58&#xa0;&#x200b;&#x3bc;mol/L in the OG and by 0.57&#xa0;&#x200b;&#x3bc;mol/L in the CG. The RVP decreased on average by 4.60&#xa0;&#x200b;mmHg in the OG and by 0.75&#xa0;&#x200b;mmHg in the CG. The difference between the two groups was significant for both parameters (P&#xa0;&#x200b;<0.001); 66% of the OG and 41% of the CG had no retinal fluid at the end of the study. After the completion of the study, the injection intervals could be extended more often in the OG patients than in the CG patients.<br><br>CONCLUSIONS: When Ocufolin forte was added to the standard therapy, RVP and Hcy were reduced to a significantly greater extent than without Ocufolin forte. In addition, Ocufolin had a positive influence on morphology and future treatment intervals with anti-VEGF therapy.},
}
@article {pmid40274966,
year = {2025},
author = {Huang, K and Schofield, C and Nguy, T and Dere, R and Wolowski, V and Siebourg-Polster, J and Dieckmann, A and Garweg, JG and Chang, M and Honigberg, L and Hackney, J and Indjeian, VB},
title = {Proteomics approach identifies aqueous humor biomarkers in retinal diseases.},
journal = {Communications medicine},
volume = {5},
number = {1},
pages = {134},
pmid = {40274966},
issn = {2730-664X},
abstract = {BACKGROUND: Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is one of the main causes of blindness in the elderly population, but the molecular pathophysiology is difficult to study due to limited access to retinal tissue. We investigated aqueous humor (AH) as an accessible surrogate for studying retinal pathophysiology.<br><br>METHODS: We applied affinity-based Olink proteomics on AH samples obtained from 30 non-AMD control, 30 intermediate AMD (iAMD) and 28 GA subjects to identify AH biomarkers associated with GA. Quantile normalization was applied to the Olink data, followed by differential abundance analysis using the limma R package. To contextualize our findings, we cross-referenced the identified proteins to gene expression datasets and AH proteomics data from diabetic retinopathy (DR) subjects.<br><br>RESULTS: Our differential abundance analysis reveals 82 significantly altered proteins in GA compared to non-AMD control. Cross-referencing with gene expression datasets indicates a majority of them are robustly expressed in the retina, particularly in retinal pigment epithelium cells. Comparison with AH proteomics data from DR subjects reveals both unique and shared biomarkers between GA and DR. Integrating these findings, we identify SMOC2 and IL-6 as top candidate GA biomarkers, warranting further investigation.<br><br>CONCLUSIONS: Our integrative analysis demonstrates a robust framework for AH biomarker discovery and identifies SMOC2 and IL-6 as promising biomarkers for GA. Our findings underscore the potential of AH proteomic profiling to advance our understanding of the underlying pathophysiology of retinal diseases.},
}
@article {pmid40273531,
year = {2025},
author = {Ashrafi, A and Runyon, W and Hu, S and Kumar, R and Catchpole, T and Singh, A and Ratnapriya, R and Csaky, KG and Sripathi, SR},
title = {Generation of human induced pluripotent stem cell lines from an age-related macular degeneration patient with hyperreflective foci overlying drusen (RFSCi002-A) and an unaffected sibling (RFSCi001-A).},
journal = {Stem cell research},
volume = {86},
number = {},
pages = {103715},
doi = {10.1016/j.scr.2025.103715},
pmid = {40273531},
issn = {1876-7753},
mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/pathology/cytology ; *Macular Degeneration/pathology/metabolism ; Cell Line ; *Retinal Drusen/pathology ; Siblings ; Tomography, Optical Coherence ; Retinal Pigment Epithelium/pathology ; Male ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, driven by retinal pigment epithelium (RPE) and photoreceptor degeneration. A key feature is drusen accumulation between the RPE and Bruch's membrane. In intermediate AMD, hyperreflective foci (HRF)-bright intraretinal lesions visible on optical coherence tomography (OCT) imaging-serve as biomarkers of disease progression. To study HRF mechanisms, we generated induced pluripotent stem cell (iPSC) lines from an AMD patient with HRF overlying drusen (RFSC4) and their unaffected sibling (RFSC3). These iPSC models offer a platform to explore disease mechanisms and develop therapies for AMD.},
}
@article {pmid40271423,
year = {2025},
author = {Stevanovic, M and Koulisis, N and Chen, T and Moysidis, SN and Burkemper, B and Toy, BC and Rao, NA and Eliott, D and Humayun, MS},
title = {Intraocular Inflammation, Safety Events, and Outcomes After Intravitreal Injection of Ranibizumab, Aflibercept, Brolucizumab, Abicipar Pegol, and Faricimab for nAMD.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251332515},
pmid = {40271423},
issn = {2474-1272},
support = {K23 EY032985/EY/NEI NIH HHS/United States ; },
abstract = {Purpose: To compare the rates of intraocular inflammation (IOI) in patients with neovascular age-related macular degeneration (nAMD) after injection of intravitreal (IVT) antivascular endothelial growth factor drugs. Methods: This study included all phase 3 randomized clinical trials of patients with nAMD treated with ranibizumab, aflibercept, brolucizumab, abicipar pegol, or faricimab. The outcomes assessed were the incidence of IOI, retinal artery occlusion (RAO), retinal vasculitis and choroiditis, endophthalmitis, and serious systemic adverse events (AEs) as well as the change in visual acuity (VA) (Early Treatment Diabetic Retinopathy Study letters) and in central retinal thickness (CRT). Results: Abicipar pegol was associated with a higher incidence of IOI than aflibercept, ranibizumab, faricimab, and sham injections, while brolucizumab was associated with a higher rate of IOI than aflibercept, faricimab, and sham injections. Abicipar pegol was also associated with a higher rate of endophthalmitis than aflibercept. Significantly more retinal vasculitis and choroiditis was seen with abicipar pegol and brolucizumab than with ranibizumab and aflibercept, respectively, and RAOs occurred more frequently with abicipar pegol and brolucizumab than with ranibizumab and aflibercept, respectively. There were no differences in the change in VA among the drugs. Treatment with brolucizumab resulted in a greater change in CRT than with abicipar pegol, aflibercept, ranibizumab, and faricimab, while treatment with faricimab resulted in a greater change in CRT than aflibercept and ranibizumab. Faricimab was associated with fewer serious systemic AEs than aflibercept. Conclusions: Abicipar pegol and brolucizumab were associated with a higher incidence of ocular AEs in phase 3 randomized controlled trials. The potential benefits of these drugs should be weighed against the AEs.},
}
@article {pmid40270623,
year = {2025},
author = {Soman, M and Jadhav, A and Balakrishnan, A and Sheth, JU and Nair, U},
title = {Proactive Post-Injection Monitoring in Brolucizumab Therapy: A Study on Intraocular Inflammation and Treatment Outcomes.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1313-1321},
pmid = {40270623},
issn = {1177-5467},
abstract = {PURPOSE: Intravitreal anti-VEGF agents, such as Brolucizumab, play a crucial role in treating neovascular age-related macular degeneration (nAMD) and Polypoidal choroidal vasculopathy (PCV). While Brolucizumab offers advantages like extended duration and fewer injections, concerns about intraocular inflammation (IOI) have emerged. This study evaluates the outcomes of a proactive monitoring protocol for Brolucizumab-treated eyes with resistant nAMD and PCV.<br><br>PATIENTS AND METHODS: A single-center retrospective study analyzed patients treated with Brolucizumab for resistant nAMD and PCV. Data on demographics, visual outcomes and IOI incidence, with the latter being confirmed by clinicians. Additional data on management strategies and follow-up adherence were also analyzed. Proactive monitoring included telephonic follow-up on day one and mandatory clinic visits on days 15 and 30. Retreatment followed a pro-re-nata (PRN) approach based on fluid persistence or visual acuity loss.<br><br>RESULTS: Between February 2022 and September 2024, 311 Brolucizumab injections were administered to 144 eyes of 121 patients, with a mean follow-up of 8.6 months. IOI occurred in 7 eyes (4.9%), with a mean onset of 32.1 days. According to the HAWK and HARRIER discomfort grading scale, IOI was categorized as mild in 2 eyes (28.6%), moderate in 3 eyes (42.9%), and severe in 2 eyes (28.6%). Symptoms varied, including blurred vision, floaters, redness, and ocular pain. Inflammation was managed with topical and oral steroids, with resolution in 6&#xa0;weeks for vasculitis and 9&#xa0;weeks for vitritis, and no cases required intravitreal agents or vitrectomy. Visual acuity improved or remained stable for most, except in one case of persistent vitritis.<br><br>CONCLUSION: This study highlights the incidence of IOI with Brolucizumab in a real-world setting, emphasizing the importance of proactive monitoring and early intervention. Despite the occurrence of inflammation, visual outcomes were generally favorable, supporting the safety of Brolucizumab when managed carefully.},
}
@article {pmid40269257,
year = {2025},
author = {Zhang, Z and Zhang, X and Zhang, R and Tan, C and Bai, J and Zhang, P and Yang, S and Ling, Y and Gao, Y},
title = {Potential to improve the burden of age-related macular degeneration: results from the Global Burden of Disease Study 2021.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {2064-2072},
pmid = {40269257},
issn = {1476-5454},
mesh = {Humans ; *Macular Degeneration/epidemiology ; Global Burden of Disease/trends ; Male ; Female ; Prevalence ; Aged ; Risk Factors ; Disability-Adjusted Life Years ; Global Health ; Middle Aged ; Aged, 80 and over ; *Cost of Illness ; Quality-Adjusted Life Years ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a critical public health issue, requiring prioritized public health strategies.<br><br>METHODS: Based on the Global Burden of Disease Study 2021, AMD burden and risk factors were analyzed, considering variables such as sex, age, and location. Age-standardized rates (ASR) were employed to evaluate and compare the burdens across different regions. Frontier analysis was used to determine the lowest achievable burden based on the Sociodemographic Index (SDI), while decomposition analysis revealed factors influencing age-related macular degeneration burden change.<br><br>RESULTS: Globally, in 2021, ASR of prevalence and disability-adjusted life years (DALYs) were 94.00 (95% UI 78.32, 114.42) per 100,000 and 6.78 (95% UI 4.70, 9.32) per 100,000 respectively. Additionally, a reduction of smoking exposure to its theoretical minimum risk exposure level (TMREL) would lead to an estimated 10.0% decrease in AMD DALYs in 2021. Frontier analysis suggested that Nepal, Iran (Islamic Republic of), and Nigeria were the top three countries with the most substantial potential for reducing disparities. Decomposition analysis indicated that population growth and aging are the primary driving factors for the increase in AMD DALYs.<br><br>CONCLUSIONS: We identify countries and territories with potential for improvement and emphasize the importance of equitable, cost-effective control strategies, particularly tobacco control.},
}
@article {pmid40268248,
year = {2025},
author = {Biber, J and Gandor, C and Becirovic, E and Michalakis, S},
title = {Retina-directed gene therapy: Achievements and remaining challenges.},
journal = {Pharmacology &amp; therapeutics},
volume = {271},
number = {},
pages = {108862},
doi = {10.1016/j.pharmthera.2025.108862},
pmid = {40268248},
issn = {1879-016X},
mesh = {*Genetic Therapy/methods ; Humans ; Dependovirus/genetics ; Animals ; *Retinal Diseases/therapy/genetics ; Genetic Vectors ; *Retina/metabolism ; Gene Transfer Techniques ; cis-trans-Isomerases/genetics ; },
abstract = {Gene therapy is an innovative medical approach that offers new treatment options for congenital and acquired diseases by transferring, correcting, inactivating or regulating genes to supplement, replace or modify a gene function. The approval of voretigene neparvovec (Luxturna), a gene therapy for RPE65-associated retinopathy, has marked a milestone for the field of retinal gene therapy, but has also helped to accelerate the development of gene therapies for genetic diseases affecting other organs. Voretigene neparvovec is a vector based on adeno-associated virus (AAV) that delivers a functional copy of RPE65 to supplement the missing function of this gene. The AAV-based gene delivery has proven to be versatile and safe for the transfer of genetic material to retinal cells. However, challenges remain in treating additional inherited as well as acquired retinopathies with this technology. Despite the high level of activity in this field, no other AAV gene therapy for retinal diseases has been approved since voretigene neparvovec. Ongoing research focuses on overcoming the current restraints through innovative strategies like AAV capsid engineering, dual-AAV vector systems, or CRISPR/Cas-mediated genome editing. Additionally, AAV gene therapy is being explored for the treatment of complex acquired diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) by targeting molecules involved in the pathobiology of the degenerative processes. This review outlines the current state of retinal gene therapy, highlighting ongoing challenges and future directions.},
}
@article {pmid40267604,
year = {2025},
author = {Zervou, MI and Tarlatzis, BC and Goulielmos, GN},
title = {Endometriosis as a risk factor for age-related macular degeneration: A nationwide population-based study and genetic aspects.},
journal = {Maturitas},
volume = {197},
number = {},
pages = {108272},
doi = {10.1016/j.maturitas.2025.108272},
pmid = {40267604},
issn = {1873-4111},
}
@article {pmid40266467,
year = {2025},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Can Stem Cell Therapy Revolutionize Ocular Disease Treatment? A Critical Review of Preclinical and Clinical Advances.},
journal = {Stem cell reviews and reports},
volume = {21},
number = {5},
pages = {1160-1185},
pmid = {40266467},
issn = {2629-3277},
mesh = {Humans ; *Stem Cell Transplantation/methods ; *Eye Diseases/therapy ; Animals ; Induced Pluripotent Stem Cells/transplantation ; },
abstract = {Stem cell therapy in regenerative medicine has a scope for treating ocular diseases. Stem cell therapy aims to repair damaged tissue and restore vision. The present review focuses on the advancements in stem cell therapies for ocular disorders, their mechanism of action, and clinical applications while addressing some outstanding challenges. Stem cells that include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells have regenerative potential for ocular repair. They differentiate into specialized ocular cell types, conduct neuroprotection, and modulate immune responses. It is emphasized in preclinical and clinical studies that stem cell therapy can treat corneal disorders such as limbal stem cell deficiency, retinal diseases like dry age macular degeneration and retinitis pigmentosa, and diabetic retinopathy. Various studies suggested that stem cells have considerable scope in glaucoma treatment by supporting retinal ganglion cell survival and optic nerve regeneration. Advanced approaches such as gene editing, organoid generation, and artificial intelligence enhance these therapies. Effective delivery to target areas, engraftment, orientation, and long-term survival of transplanted cells need optimization. Issues such as immune rejection and tumorigenicity must be addressed. This approach is further hindered by regulatory issues and overly complicated approval processes and trials. Ethical issues related to sourcing embryonic stem cells and patient consent complicate the issue. The cost of manufacturing stem cells and their accessibility are other factors posing potential barriers to widespread application. These regulatory, ethical, and economic issues must be tackled if stem cell treatments are to be made safe, accessible, and effective. Future studies will include refining therapeutic protocols, scaling manufacturing processes, and overcoming socio-economic barriers, eventually improving clinical outcomes.},
}
@article {pmid40266369,
year = {2025},
author = {Jung, B and Yagi, H and Kuo, A and Dorweiler, TF and Aikawa, M and Kasai, T and Singh, SA and Dannenberg, AJ and Fu, Z and Niaudet, C and Smith, LEH and Hla, T},
title = {ApoM-bound S1P acts via endothelial S1PR1 to suppress choroidal neovascularization and vascular leakage.},
journal = {Angiogenesis},
volume = {28},
number = {2},
pages = {24},
pmid = {40266369},
issn = {1573-7209},
support = {R01 AG078602/AG/NIA NIH HHS/United States ; R01 EY031715/EY/NEI NIH HHS/United States ; EY031715/NH/NIH HHS/United States ; },
mesh = {*Choroidal Neovascularization/pathology/metabolism/genetics/drug therapy ; Animals ; *Apolipoproteins M/metabolism ; *Lysophospholipids/metabolism ; *Sphingosine/analogs &amp; derivatives/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism ; Humans ; Mice ; Mice, Knockout ; *Receptors, Lysosphingolipid/metabolism ; *Capillary Permeability/drug effects ; Mice, Transgenic ; Mice, Inbred C57BL ; *Apolipoproteins/metabolism ; Male ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of vision loss worldwide. Current standard of care is repetitive intraocular injections of vascular endothelial growth factor (VEGF) inhibitors, although responses may be partial and non-durable. We report that circulating sphingosine 1-phosphate (S1P) carried by apolipoprotein M (ApoM) acts through the endothelial S1P receptor 1 (S1PR1) to suppress choroidal neovascularization (CNV) in mouse laser-induced CNV, modeling nAMD. In humans, low plasma ApoM levels were associated with increased choroidal and retinal pathology. Additionally, endothelial S1pr1 knockout and overexpressing transgenic mice showed increased and reduced CNV lesion size, respectively. Systemic administration of ApoM-Fc, an engineered S1P chaperone protein, not only attenuated CNV to an equivalent degree as anti-VEGF antibody treatment but also suppressed pathological vascular leakage. We suggest that modulating circulating ApoM-bound S1P action on endothelial S1PR1 provides a novel therapeutic strategy to treat nAMD.},
}
@article {pmid40265403,
year = {2025},
author = {Lee, D and Kim, SJ and Lee, J},
title = {Novel Therapeutic Approaches for Treatment of Diabetic Retinopathy and Age-Related Macular Degeneration.},
journal = {Vision (Basel, Switzerland)},
volume = {9},
number = {2},
pages = {},
pmid = {40265403},
issn = {2411-5150},
support = {RS-2024-00438689//the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea/ ; },
abstract = {Retina, a light-sensitive layer of tissue of the eye, requires high levels of oxygen for its physiology. Retinal ischemia occurs due to inadequate supply of blood to the retina and choroid. Retinal ischemia is implicated in the development or progression of many ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). To date, anti-vascular endothelial growth factor (VEGF) treatment has been widely used to manage neovascular diseases associated with retinal ischemia. Nonetheless, a substantial number of patients with DR or AMD still suffer from incomplete response and adverse effects related to its therapy with limitations. Therefore, research scientists have been developing and finding novel treatments to protect against or prevent vision loss in those diseases. In this review article, we summarize the recent novel therapeutic approaches for the treatment of ischemic retinopathy (e.g., cell therapy, advanced molecular targeting, or drug delivery). This summary enables further research to obtain more solid evidence of novel effective drug development in retinal ischemic diseases.},
}
@article {pmid40264207,
year = {2025},
author = {Zhao, Y and Zhang, Y and Li, J and Zhang, Y and Qu, Y},
title = {The role of IGF2BP2 in macrophage-mediated NLRP3 inflammasome activation in the pathogenesis of dry AMD.},
journal = {Biology direct},
volume = {20},
number = {1},
pages = {57},
pmid = {40264207},
issn = {1745-6150},
mesh = {*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *RNA-Binding Proteins/metabolism/genetics ; *Inflammasomes/metabolism ; *Macrophages/metabolism ; Animals ; Mice ; *Macular Degeneration/metabolism/genetics ; Mice, Inbred C57BL ; Humans ; },
abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is a common chronic degenerative eye disease for which there is currently no effective treatment. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a recently identified m6A reader that binds RNA and maintains its stability, thereby participating in various biological processes. However, its role in dry AMD remains unclear.<br><br>METHODS: In this study, we investigated the role of IGF2BP2 in macrophage NLRP3 inflammasomes using a sodium iodate-induced dry AMD model.<br><br>RESULTS: Our results demonstrated that IGF2BP2 is highly expressed in the retinal-choroidal tissue induced by sodium iodate, with its effects primarily occurring in macrophages. The loss of IGF2BP2 ameliorating dry AMD. Mechanistically, methylated NLRP3 transcripts were subsequently directly recognized by the specific m 6&#xa0;A "reader", IGF2BP2, to prevent NLRP3 mRNA degradation. Furthermore, in in vivo experiments, to maintain the eye's "immune privilege", we employed mesoporous silica-based cell therapy to target and regulate macrophage IGF2BP2, providing a foundation for the evaluation and translation of therapies targeting this gene.<br><br>CONCLUSION: our study reveals that the molecular mechanism of dry AMD pathogenesis involves IGF2BP2-mediated NLRP3 inflammasome activation in macrophages, highlighting IGF2BP2 as a promising biomarker and therapeutic target for dry AMD treatment.},
}
@article {pmid40261663,
year = {2025},
author = {Boldu-Roig, J and Sorli-Clemente, E and Kuljuh-Causevic, A and Loras, A and Anton, A and Martinez-Cadenas, C},
title = {Iris Pigmented Lesions: Unraveling the Genetic Basis of Iris Freckles and Nevi.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {62},
pmid = {40261663},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Middle Aged ; *Iris Neoplasms/genetics/pathology ; Adult ; *Nevus, Pigmented/genetics/pathology ; *Iris/pathology ; Aged ; Interferon Regulatory Factors/genetics ; Eye Color/genetics ; Ubiquitin-Protein Ligases/genetics ; Young Adult ; *Iris Diseases/genetics ; Adolescent ; Aged, 80 and over ; Antigens, Neoplasm ; Membrane Transport Proteins ; },
abstract = {PURPOSE: To investigate the diversity of pigmented benign lesions in the human iris, aiming to provide insights for forensic, biomedical, and ophthalmological research.<br><br>METHODS: A cohort of 1014 individuals of Spanish descent was analyzed. Digital slit-lamp photographs were used to evaluate iris pigmentation traits, including iris freckles, iris nevi, iris color, and the presence of a pigmented collarette. A candidate gene association study was performed on these pigmentation traits.<br><br>RESULTS: Both iris freckles and nevi were associated with increased age, female sex, pigmented collarette, and eye color (mainly green). Additionally, higher freckle and nevus counts were observed in participants with more facial freckles and cutaneous nevi and were positively associated with each other. After adjustment, a positive significant association was identified between the presence of iris freckles and genetic variants in the IRF4, HERC2, and OCA2 genes, as well as SLC45A2, although only in females. The prevalence of iris nevi was significantly lower compared to freckles. The presence of iris nevi also showed positive associations with genetic variants in IRF4 and HERC2, plus TYR in brown-eyed individuals only. No association was identified between MC1R, the major cutaneous freckle gene, and the presence of iris freckles or nevi.<br><br>CONCLUSIONS: The genetic basis of iris freckles and nevi reveals associations with well-known pigmentation genes (particularly IRF4), as well as eye color, sex, and age. These findings contribute to our understanding of iris pigmented benign lesions and their potential implications in conditions such as uveal melanoma, age-related macular degeneration, or solar damage.},
}
@article {pmid40261662,
year = {2025},
author = {Peng, Y and Zhang, Y and Kam, KW and Wong, G and Ho, M and Sezto, S and Au, S and Zhang, X and Ng, MPH and Ip, P and Young, A and Pang, CP and Tham, CC and Chen, LJ and Yam, JC},
title = {Associations of Cardiovascular Health and New-Onset Age-Related Macular Diseases From UK Biobank.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {63},
pmid = {40261662},
issn = {1552-5783},
mesh = {Humans ; Male ; Female ; *Macular Degeneration/epidemiology ; Aged ; United Kingdom/epidemiology ; Incidence ; *Cardiovascular Diseases/epidemiology ; Middle Aged ; Risk Factors ; Follow-Up Studies ; *Biological Specimen Banks ; Aged, 80 and over ; Longitudinal Studies ; Proportional Hazards Models ; UK Biobank ; },
abstract = {PURPOSE: This study aimed to investigate the correlation between cardiovascular health (CVH), evaluated through the Life's Essential 8 (LE8) score, and the risk of new-onset age-related macular degeneration (AMD).<br><br>METHODS: This longitudinal analysis included 271,274 participants who were free of both cardiovascular diseases and AMD at baseline. The LE8 score was classified into three categories: low (<50 points), moderate (50 to <80 points), and high (&#x2265;80 points), with higher scores indicating better CVH. Cox proportional hazards models were used to explore the relationships between the CVH and AMD incidence. Furthermore, the population attributable risk (PAR%) was calculated for CVH and each individual metric.<br><br>RESULTS: During an average follow-up duration of 10.9 years, a total of 7468 (2.8%) cases of AMD were documented. Individuals with moderate and high CVH levels had a 14% (hazard ratio [HR] = 0.86; 95% confidence interval [CI], 0.78-0.94) and 23% (HR = 0.77; 95% CI, 0.69-0.86) reduced risk of developing AMD, respectively. A linear dose-response relationship was identified between the cumulative LE8 score and the incidence of AMD. Attaining optimal CVH in all individuals could potentially avert 9.4% (95% CI, 3.7%-15.1%) of AMD cases. Among the CVH metrics, ideal blood glucose and blood pressure levels were related to a reduction of 3.3% and 8.7% in AMD cases, respectively.<br><br>CONCLUSIONS: Enhanced CVH is significantly associated with a reduced risk of developing AMD. Promoting CVH through the LE8 guideline might potentially contribute to the prevention of AMD.},
}
@article {pmid40261298,
year = {2025},
author = {Fortmann, SD and Frey, BF and Rosencrans, RF and Adu-Rutledge, Y and Ready V, E and Kilchrist, KV and Welner, RS and Boulton, ME and Saban, DR and Grant, MB},
title = {Prenatally derived macrophages support choroidal health and decline in age-related macular degeneration.},
journal = {The Journal of experimental medicine},
volume = {222},
number = {7},
pages = {},
pmid = {40261298},
issn = {1540-9538},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; P30 EY005722/EY/NEI NIH HHS/United States ; F30EY033198/NH/NIH HHS/United States ; /DK/NIDDK NIH HHS/United States ; },
mesh = {*Macular Degeneration/pathology/metabolism/immunology ; *Macrophages/metabolism/pathology/immunology ; Humans ; Animals ; *Choroid/pathology/immunology/metabolism ; Mice ; Female ; Mice, Inbred C57BL ; Male ; },
abstract = {Hallmark findings in age-related macular degeneration (AMD) include the accumulation of extracellular lipid and vasodegeneration of the choriocapillaris. Choroidal inflammation has long been associated with AMD, but little is known about the immune landscape of the human choroid. Using 3D multiplex immunofluorescence, single-cell RNA sequencing, and flow cytometry, we unravel the cellular composition and spatial organization of the human choroid and the immune cells within it. We identify two populations of choroidal macrophages with distinct FOLR2 expression that account for the majority of myeloid cells. FOLR2+ macrophages predominate in the nondiseased eye, express lipid-handling machinery, uptake lipoprotein particles, and contain high amounts of lipid. In AMD, FOLR2+ macrophages are decreased in number and exhibit dysfunctional lipoprotein metabolism. In mice, FOLR2+ macrophages are negative for the postnatal fate-reporter Ms4a3, and their depletion causes an accelerated AMD-like phenotype. Our results show that prenatally derived resident macrophages decline in AMD and are implicated in multiple hallmark functions known to be compromised in the disease.},
}
@article {pmid40260361,
year = {2025},
author = {Schimmelbusch, K and Koci, M and Hainsworth, D and Brockbank, DT},
title = {Spontaneous Bilateral Drusen Regression Without Atrophy in an Octogenarian With Gilbert's Syndrome: A Case Report.},
journal = {Cureus},
volume = {17},
number = {3},
pages = {e80993},
pmid = {40260361},
issn = {2168-8184},
abstract = {We document significant drusen regression without atrophy (DRwoA) in a patient with dry age-related macular degeneration (AMD) and concomitant hyperbilirubinemia. Serial optical coherence tomography (OCT) and fundus images were used to monitor drusen progression in the patient. Fundus photography of the macula revealed a dramatic improvement in visible drusen in each eye over the course of 2020-2023. Only a few small drusen were visible in the right eye, while moderate to intermediate-to-large soft drusen were present in the left eye. OCT imaging also demonstrated significant improvement in drusen in both eyes compared to previous years. Average foveal thickness measurements from 2018 to 2023 showed a significant and steady decline, from 298 µm to 291 µm in the right eye and from 305 µm to 273 µm in the left eye. We report significant drusen regression in a patient with Gilbert's syndrome and dry AMD. Further investigation into the prevalence and severity of AMD in patients with Gilbert's syndrome is warranted. Additionally, further study of the potential therapeutic application of Spirulina in treating inflammatory conditions such as AMD is reasonable.},
}
@article {pmid40259096,
year = {2025},
author = {Jeong, A and de Jesus, FR and Baek, SC and Sagong, M},
title = {Comparison of one-year outcomes between aflibercept and brolucizumab for treatment-naïve pachychoroid neovasculopathy.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13674},
pmid = {40259096},
issn = {2045-2322},
mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Female ; Male ; Aged ; Retrospective Studies ; *Choroidal Neovascularization/drug therapy/pathology ; Visual Acuity/drug effects ; Treatment Outcome ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Middle Aged ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Choroid/pathology/drug effects/blood supply ; Tomography, Optical Coherence ; Aged, 80 and over ; },
abstract = {Pachychoroid neovasculopathy (PNV) is characterized by increased choroidal thickness, choroidal hyperpermeability, and fluid accumulation. Given its distinct pathophysiology, PNV requires management with anti-VEGF therapy, as its treatment response differs from typical neovascular age-related macular degeneration (nAMD). This study aimed to compare the one-year visual and anatomic outcomes between aflibercept and brolucizumab for treatment-naive PNV. A retrospective medical chart review was performed for consecutive 45 eyes from 45 patients with treatment-naive PNV initially treated with thee monthly intravitreal aflibercept (n = 28, 2.0 mg/0.05 ml) or brolucizumab (n = 17, 6.0 mg/0.05 ml) followed by as-needed regimen, followed up for at least 12 months. Best corrected visual acuity (BCVA) and OCT parameters including central macular thickness (CMT), subfoveal choroidal thickness (SFCT), changes in thickness of choriocapillaris (CC)/Sattler and Haller layer, choroidal vascularity index (CVI) were evaluated at baseline, 3-month, 6-months, and 12-month visits. At the 12-month visit, BCVA improved and CMT decreased significantly in both brolucizumab-treated group and in the aflibercept-treated group, suggesting comparable visual improvement in both groups (p < 0.05 for all). Mean SFCT were significantly reduced through 12 months of treatment in both aflibercept and brolucizumab groups (p = 0.001 for both). Decrease in CMT from the baseline for the brolucizumab-treated group was significantly greater than for the aflibercept group at month 12 (p = 0.038). Decrease in the mean SFCT and Haller layer thickness were significantly greater for the brolucizumab-treated group than that for the aflibercept-treated group at month 3 and 6 (p = 0.013 and p = 0.035). An increase of the CVI from baseline was observed only in the brolucizumab group at month 12 (p = 0.041). CC flow density did not change after 12 months in both groups. The rate of dry macula at month 12 did not differ significantly between the two groups (78.6% in aflibercept group vs. 82.4% in brolucizumab group, p = 0.104). These findings suggested that as-needed administration of brolucizumab demonstrated comparable visual outcomes to aflibercept in treatment-naïve PNV eyes. Additionally, over 12 months, brolucizumab showed a greater effect in reducing CMT, SFCT, and Haller layer thickness, as well as increasing CVI, suggesting potential choroidal morphology remodeling.},
}
@article {pmid40258439,
year = {2025},
author = {Obana, A},
title = {Measurement of skin carotenoids and their association with diseases: a narrative review.},
journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids},
volume = {1870},
number = {5},
pages = {159612},
doi = {10.1016/j.bbalip.2025.159612},
pmid = {40258439},
issn = {1879-2618},
mesh = {Humans ; *Carotenoids/metabolism/analysis ; *Skin/metabolism/chemistry ; Biomarkers/metabolism/analysis ; Macular Degeneration/metabolism ; Metabolic Syndrome/metabolism ; Asthma/metabolism ; Cognitive Dysfunction/metabolism ; Atherosclerosis/metabolism ; },
abstract = {Skin carotenoids are highly correlated with blood carotenoid concentrations and can be measured noninvasively using optical methods. Skin carotenoid levels are widely used in nutritional education as indicators of fruit and vegetable intake; however, research on their use as biomarkers for disease prevention is limited. This narrative review outlines methods for measuring skin carotenoid levels and describes the diseases in which the relationship between skin carotenoids and diseases has been examined, including atherosclerotic cardiovascular disease, metabolic syndrome, pediatric asthma, age-related macular degeneration, and cognitive impairment.},
}
@article {pmid40258194,
year = {2025},
author = {Morgan, RA and Weng, PJ and Stinnett, SS and Grewal, DS and Fekrat, S},
title = {Dopaminergic Therapies May Decrease Risk of Early and Intermediate Non-exudative Age-related Macular Degeneration Progression.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {7},
pages = {416-421},
doi = {10.3928/23258160-20250326-02},
pmid = {40258194},
issn = {2325-8179},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Disease Progression ; Aged ; *Dopamine Agents/therapeutic use/administration &amp; dosage ; Follow-Up Studies ; *Visual Acuity ; Aged, 80 and over ; Tomography, Optical Coherence/methods ; Middle Aged ; *Geographic Atrophy/diagnosis/drug therapy ; *Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; },
abstract = {BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) is a leading cause of vision loss, with progression to geographic atrophy (GA) posing a significant challenge. This study aimed to assess whether dopaminergic therapies (DMTs) reduce risk of AMD progressing to GA.<br><br>PATIENTS AND METHODS: A retrospective cohort study analyzed electronic health records of 320 patients (449 eyes) with early or intermediate nonexudative AMD at Duke Eye Center from 2014 to 2024. Of these, 80 patients (110 eyes) were on DMTs, and 240 (339 eyes) served as controls. GA progression was evaluated annually over 5 years.<br><br>RESULTS: GA progression was lower in the DMT group across all intervals, with lifetime rates of 9.4% in the non-DMT group versus 2.7% in the DMT group (P < 0.05). Multivariate analysis showed a significant protective effect (odds ratio 0.08, P < 0.001).<br><br>CONCLUSION: DMTs may significantly reduce risk of AMD progressing to GA, warranting further research. [Ophthalmic Surg Lasers Imaging Retina 2025;56:416-421.].},
}
@article {pmid40257787,
year = {2025},
author = {Wang, W and Ren, R and Liu, Y and Ye, X and Zhang, R and Xi, L and Wang, L and Zhang, Y and Zhang, Y and Wang, D},
title = {Life's Essential 8, Genetic Susceptibility, and the Risk of Age-Related Macular Degeneration: A Prospective Cohort Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {54},
pmid = {40257787},
issn = {1552-5783},
mesh = {Humans ; Prospective Studies ; Female ; Male ; *Genetic Predisposition to Disease ; *Macular Degeneration/genetics/epidemiology ; Aged ; Incidence ; Middle Aged ; Risk Factors ; United Kingdom/epidemiology ; Cardiovascular Diseases/epidemiology ; Proportional Hazards Models ; Follow-Up Studies ; Aged, 80 and over ; },
abstract = {PURPOSE: We determined the association between Life's Essential 8 (LE8) scores and AMD incidence and ascertained whether genetic susceptibility modifies it.<br><br>METHODS: This prospective cohort study included 268,634 UK Biobank study participants with high, moderate, or low cardiovascular health based on LE8 scores. High and low cardiovascular health corresponded to the lowest and highest cardiovascular disease risks, respectively. The hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD were estimated using Cox proportional hazards models. The dose-response relationships were evaluated using restricted cubic spline analysis. Stratified analyses using the AMD-polygenic risk score categories were used to assess potential modification. A composite variable combined LE8 and AMD-polygenic risk to examine their joint effects.<br><br>RESULTS: Over an average of 13.76 years, 5253 participants developed AMD. Compared with the lowest cardiovascular health, moderate and high cardiovascular health had adjusted HRs of 0.86 (95% CI, 0.76, 0.97) and 0.79 (0.69, 0.91), respectively. Each standard deviation increase in the LE8 score corresponded to an HR of 0.93 (0.91, 0.96). The LE8 behavior (HR = 0.94 [0.91, 0.96]) and biological (HR = 0.97 [0.95, 1.00]) subscale scores were inversely associated with AMD, whereas the blood lipids component was positively associated (HR = 1.07 [1.04, 1.10]). The AMD-polygenic risk and LE8 scores showed no significant interaction. The HR for having low AMD-polygenic risk and high cardiovascular health relative to having high AMD-polygenic risk and low cardiovascular health was 0.47 (0.37, 0.58).<br><br>CONCLUSIONS: Maintaining good cardiovascular health can reduce AMD incidence regardless of genetic background.},
}
@article {pmid40257785,
year = {2025},
author = {Goerdt, L and Clark, ME and Thomas, TN and Gao, L and McGwin, G and Hammer, M and Crosson, JN and Sloan, KR and Owsley, C and Curcio, CA},
title = {Fluorescence Lifetime Imaging Ophthalmoscopy, Vision, and Chorioretinal Asymmetries in Aging and Age-Related Macular Degeneration: ALSTAR2.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {56},
pmid = {40257785},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Ophthalmoscopy/methods ; Aged ; *Macular Degeneration/physiopathology/diagnosis ; Male ; *Aging/physiology ; Follow-Up Studies ; Dark Adaptation/physiology ; *Visual Acuity/physiology ; Aged, 80 and over ; Fluorescein Angiography/methods ; Optical Imaging/methods ; *Choroid/pathology ; *Retina/physiopathology/pathology ; },
abstract = {PURPOSE: Eyes with age-related macular degeneration (AMD) and some healthy aged eyes exhibit risk-indicating delays in rod-mediated dark adaptation (RMDA) and prolonged long spectral channel (LSC) lifetimes by fluorescence lifetime imaging ophthalmoscopy (FLIO) in the Early Treatment Diabetic Retinopathy Study (ETDRS) outer ring, especially nasally. To learn FLIO's potential for AMD detection, we correlate FLIO to RMDA.<br><br>METHODS: The ALSTAR2 follow-up cohort underwent FLIO, color fundus photography, two-wavelength autofluorescence (for macular pigment optical density [MPOD]), visual function testing, including RMDA (rod intercept time [RIT]). AMD was staged by the Age-Related Eye Disease Study (AREDS) 9-step at baseline and follow-up. In pseudophakic eyes with high-quality FLIO, mean intensity maps and meridian plots were created. Vision data were analyzed using linear regression and Spearman's r.<br><br>RESULTS: Of 155 eyes (155 participants [75 &#xb1; 5.0 years; 60.7% female participants]), 67 eyes were healthy, 38 had early (e)AMD, and 50 had intermediate (i)AMD (P = 0.02). LSC lifetimes were longest in iAMD in all ETDRS regions (P < 0.01) and short spectral channel (SSC) lifetimes in inner and outer rings (P < 0.01). The LSC pattern manifested in 65 of 88 AMD eyes and 30 of 67 healthy eyes. Lifetimes were longest on the nasal meridian and shortest on temporal. LSC lifetimes in the inner and outer rings correlated strongly with RIT (r = 0.68). A stable subgroup had short LSC lifetimes and short RIT. SSC correlated weakly with MPOD.<br><br>CONCLUSIONS: Prolonged lifetimes in AMD exhibit spatial asymmetry, suggesting mechanisms beyond retinal cells and including choroid. Lifetimes correlate with delayed RMDA, potentially indicating risk for AMD onset and early progression. Further research into SSC signal sources is warranted.},
}
@article {pmid40257783,
year = {2025},
author = {Pan, SY and Weng, CH and Tsai, SF and Lin, HJ and Lin, JF and Lin, CH and Wang, IJ and Chou, CC},
title = {Use of SGLT2 Inhibitors Versus DPP-4 Inhibitors and Age-Related Macular Degeneration in Patients WithType 2 Diabetes: A Multinational Cohort Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {58},
pmid = {40257783},
issn = {1552-5783},
mesh = {Humans ; *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy/complications ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Male ; Female ; Retrospective Studies ; Aged ; Middle Aged ; *Macular Degeneration/epidemiology/prevention &amp; control/etiology ; *Hypoglycemic Agents/therapeutic use ; Follow-Up Studies ; Incidence ; },
abstract = {PURPOSE: To compare the impact of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors on age-related macular degeneration (AMD) risk among patients with type 2 diabetes mellitus (T2DM).<br><br>METHODS: This multinational, retrospective cohort study used electronic medical records from healthcare institutions across 21 countries. Adults 50 years or older with T2DM who had a prior prescription of metformin and initiated SGLT2 or DPP-4 inhibitors from 2013 to 2023 were included. The SGLT2 and DPP-4 inhibitor groups were propensity score matched in a 1:1 ratio to balance baseline characteristics and were followed for up to 5 years to observe the occurrence of AMD. Statistical analysis was performed using the Cox proportional hazards model and Kaplan-Meier analysis.<br><br>RESULTS: Our final analysis included 20,966 T2DM patients prescribed SGLT2 inhibitors and 20,966 prescribed DPP-4 inhibitors. Compared to the DPP-4 inhibitor group, the SGLT2 inhibitor group was associated with significantly lower risks of AMD (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.58-0.85) and dry AMD (HR, 0.61; 95% CI, 0.46-0.80) but not wet AMD (HR, 0.74; 95% CI, 0.48-1.16). SGLT2 inhibitors compared with DPP-4 inhibitors were linked to a reduced risk of AMD in the White population, patients prescribed empagliflozin or dapagliflozin, and individuals with glycated hemoglobin < 8.5%, estimated glomerular filtration rate &#x2265; 60 mL/min/1.73 m2, hypertension, or dyslipidemia, regardless of body mass index level.<br><br>CONCLUSIONS: In patients with T2DM, those prescribed SGLT2 inhibitors may experience lower risks of AMD and dry AMD compared to those prescribed DPP-4 inhibitors.},
}
@article {pmid40257031,
year = {2025},
author = {Du, Y and Dang, Y},
title = {Recent Advances in Understanding the Role of PEST Sequence- Containing Proteins in Retinal Neovascularization.},
journal = {Current drug targets},
volume = {26},
number = {9},
pages = {653-663},
pmid = {40257031},
issn = {1873-5592},
support = {WJLX2022165//Research Project for Medical Education in Henan Province/ ; 232102521033//International Cooperation Project of Henan Province/ ; },
mesh = {Humans ; *Retinal Neovascularization/metabolism/drug therapy/pathology ; Animals ; Signal Transduction ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Proteolysis ; Degrons ; },
abstract = {Recent studies have identified significant advancements in understanding the role of PEST sequence-containing proteins in retinal neovascularization. Retinal neovascularization, a critical pathological process, leads to severe visual impairment associated with conditions such as diabetic retinopathy, retinopathy of prematurity, and neovascular age-related macular degeneration. These conditions represent the leading causes of blindness worldwide. Although initially effective, current anti-VEGF treatments can lose efficacy over time and impose a burden due to frequent administrations, highlighting the need for novel therapeutic targets. PEST sequences, characterized by proline, glutamic acid, serine, and threonine enrichment, are structural motifs within proteins that target them for rapid degradation via the ubiquitin-proteasome pathway. Beyond influencing protein degradation, PEST sequences are crucial in regulating angiogenesis and inflammation, essential factors in retinal disease progression. This review focuses on the dual regulatory roles of PEST sequences in VEGFR-2 degradation and stabilization, crucial receptors in angiogenic signaling, as well as their involvement in essential signaling pathways including Notch and JAK/STAT. These findings suggest that PEST sequences could serve as promising new therapeutic targets to control pathological neovascularization and associated inflammatory responses, paving the way for more effective treatments in retinal diseases. Furthermore, advances in gene editing technologies and innovative drug delivery systems enhance the potential for the development of PEST sequence-targeted therapies, offering promising avenues for future clinical applications.},
}
@article {pmid40256033,
year = {2025},
author = {Gagliardi, OM and Alisi, L and Visioli, G and Dini, F and Albanese, GM and Scordari, S and Marenco, M and Lambiase, A and Giustolisi, R},
title = {OCT predictors of retinal atrophy in neovascular age-related macular degeneration treated with aflibercept.},
journal = {International journal of ophthalmology},
volume = {18},
number = {4},
pages = {648-655},
pmid = {40256033},
issn = {2222-3959},
abstract = {AIM: To identify optical coherence tomography (OCT) features present at the diagnosis of neovascular age-related macular degeneration (nAMD) that could predict retinal atrophy (RA) and visual performance in patients treated with intravitreal aflibercept.<br><br>METHODS: OCT data collected at the time of nAMD diagnosis (T0), after the first (T1) and third (T2) intravitreal aflibercept injection, and 5y post-diagnosis (T3) were analyzed. The study included 46 eyes from patients undergoing treatment. The association of OCT features with RA and visual acuity (VA) development over time were evaluated.<br><br>RESULTS: Patients with RA at T3 exhibited worse VA (35.19&#xb1;5.7 vs 8.90&#xb1;2.3, P<0.001) and a lower rate of improvement or stability at T2 (90.48% vs 56.00%, P=0.019) and T3 (85.71% vs 8.00%, P<0.001). The development of RA at T3 was linked with type 2 macular neovascularization (MNV; 4.76% vs 36.00%, P=0.013), thinner outer nuclear layer (ONL, 88.89&#xb1;7.82 &#xb5;m vs 71.38&#xb1;14.14 &#xb5;m, P=0.033), presence of intraretinal fluid (IRF, 42.86% vs 80.00%, P=0.014), presence of IRF without subretinal fluid at T0 (SRF, 4.76% vs 32.00%, P=0.027), and reduced central foveal thickness at T3 (CFT, 190.14&#xb1;22.79 &#xb5;m vs 124.32&#xb1;14.35 &#xb5;m, P<0.001). The presence of SRF with or without IRF at the diagnosis was comparable between the two groups (90.48% vs 68.00%; P=0.084).<br><br>CONCLUSION: Type 2 MNV, reduces ONL and CFT, and IRF presence at baseline may signal a higher risk of RA in treatment-naive nAMD patients, underscoring the importance of these OCT features in early risk assessment and management strategies.},
}
@article {pmid40255074,
year = {2025},
author = {Kasem, E and Watfa, M and Afif, A and Hasan, R and Mansour, M and Almhmoud, H and Zaino, B},
title = {Optogenetic therapy for retinal degenerative diseases: A review.},
journal = {European journal of ophthalmology},
volume = {35},
number = {5},
pages = {1901-1920},
doi = {10.1177/11206721251335560},
pmid = {40255074},
issn = {1724-6016},
mesh = {Humans ; *Optogenetics/methods ; *Genetic Therapy/methods ; *Retinal Degeneration/therapy/genetics ; Animals ; },
abstract = {Optogenetics, a cutting-edge tool in novel gene manipulation and drug discovery, holds significant therapeutic potential for a variety of neurological disorders, including retinal diseases. Retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), significantly impair quality of life and cause severe visual impairment due to limited treatment options and a general lack of awareness. The increasing incidence of these degenerative conditions underscores the need for innovative solutions, such as optogenetics. Optogenetic therapy introduces genes coding for light-sensitive proteins, which are controlled by light signals to make neurons photosensitive. This precise targeting approach does not require specific gene intervention and can bypass dysfunctional photoreceptors, offering a treatment option for various degenerative and dystrophic eye diseases. Successful outcomes in patients with late-stage genetic retinal diseases and numerous clinical trials suggest that optogenetics could be an effective treatment for humans. This review provides an overview of the current landscape of optogenetic therapy, discusses its challenges, and summarizes the findings of ongoing clinical trials for neural and visual restoration.},
}
@article {pmid40254246,
year = {2025},
author = {Arrigo, A and Cremona, O and Aragona, E and Casoni, F and Consalez, G and Dogru, RM and Hauck, SM and Antropoli, A and Bianco, L and Parodi, MB and Bandello, F and Grosche, A},
title = {Müller cells trophism and pathology as the next therapeutic targets for retinal diseases.},
journal = {Progress in retinal and eye research},
volume = {106},
number = {},
pages = {101357},
doi = {10.1016/j.preteyeres.2025.101357},
pmid = {40254246},
issn = {1873-1635},
mesh = {Humans ; *Ependymoglial Cells/physiology/pathology ; *Retinal Diseases/pathology/therapy/physiopathology ; Animals ; *Retina/pathology ; },
abstract = {Müller cells are a crucial retinal cell type involved in multiple regulatory processes and functions that are essential for retinal health and functionality. Acting as structural and functional support for retinal neurons and photoreceptors, Müller cells produce growth factors, regulate ion and fluid homeostasis, and facilitate neuronal signaling. They play a pivotal role in retinal morphogenesis and cell differentiation, significantly contributing to macular development. Due to their radial morphology and unique cytoskeletal organization, Müller cells act as optical fibers, efficiently channeling photons directly to the photoreceptors. In response to retinal damage, Müller cells undergo specific gene expression and functional changes that serve as a first line of defense for neurons, but can also lead to unwarranted cell dysfunction, contributing to cell death and neurodegeneration. In some species, Müller cells can reactivate their developmental program, promoting retinal regeneration and plasticity-a remarkable ability that holds promising therapeutic potential if harnessed in mammals. The crucial and multifaceted roles of Müller cells-that we propose to collectively call "Müller cells trophism"-highlight the necessity of maintaining their functionality. Dysfunction of Müller cells, termed "Müller cells pathology," has been associated with a plethora of retinal diseases, including age-related macular degeneration, diabetic retinopathy, vitreomacular disorders, macular telangiectasia, and inherited retinal dystrophies. In this review, we outline how even subtle disruptions in Müller cells trophism can drive the pathological cascade of Müller cells pathology, emphasizing the need for targeted therapies to preserve retinal health and prevent disease progression.},
}
@article {pmid40253505,
year = {2025},
author = {Viggiano, P and Boscia, G and Clemente, A and Laterza, M and Termite, AC and Pignataro, MG and Salvelli, A and Borrelli, E and Reibaldi, M and Giannaccare, G and Alessio, G and Boscia, F},
title = {Photobiomodulation-induced choriocapillaris perfusion enhancement and outer retinal remodelling in intermediate age-related macular degeneration: a promising therapeutic approach with short-term results.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {2057-2063},
pmid = {40253505},
issn = {1476-5454},
mesh = {Humans ; *Choroid/blood supply ; Male ; Female ; Retrospective Studies ; Aged ; Visual Acuity/physiology ; Pilot Projects ; *Macular Degeneration/physiopathology/radiotherapy ; Retinal Drusen/physiopathology/pathology ; *Low-Level Light Therapy/methods ; Aged, 80 and over ; Tomography, Optical Coherence ; Fluorescein Angiography ; Capillaries/radiation effects ; Regional Blood Flow/physiology ; Middle Aged ; },
abstract = {PURPOSE: To evaluate the effects of photobiomodulation (PBM) on choriocapillaris (CC) perfusion and drusen volume in patients with intermediate age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective pilot study, 30 patients receiving PBM therapy and 30 age-matched controls were analysed. Treatment consisted of 8 sessions over 4 weeks using the EYE-LIGHT&#xae; device. Best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), mean drusen volume (MDV), and CC flow deficit percentage (FD%) were evaluated at baseline and 2-month follow-up.<br><br>RESULTS: The PBM group showed significant improvements in BCVA (&#x394; +3.2&#x2009;&#xb1;&#x2009;1.4 letters, p&#x2009;=&#x2009;0.042), reduction in drusen volume (&#x394; -0.003&#x2009;&#xb1;&#x2009;0.001&#x2009;mm&#xb3;, p&#x2009;=&#x2009;0.028), and decrease in choriocapillaris FD% (&#x394; -3.1&#x2009;&#xb1;&#x2009;1.4%, p&#x2009;=&#x2009;0.024), while no significant changes were observed in the control group. Changes in choriocapillaris FD% correlated with BCVA improvement (r&#x2009;=&#x2009;-0.54, p&#x2009;=&#x2009;0.002) and drusen volume reduction (r&#x2009;=&#x2009;0.35, p&#x2009;=&#x2009;0.042).<br><br>CONCLUSIONS: PBM therapy induces significant choriocapillaris remodelling in intermediate AMD, associated with functional improvement and drusen volume reduction. These findings suggest a potential therapeutic role of PBM in modulating choroidal perfusion in AMD.},
}
@article {pmid40253504,
year = {2025},
author = {Crincoli, E and Parravano, MC and Sacconi, R and Costanzo, E and Polito, MS and Ferro Desideri, L and Querques, G},
title = {Updates on novel and traditional OCT and OCTA biomarkers in nAMD.},
journal = {Eye (London, England)},
volume = {39},
number = {9},
pages = {1662-1672},
pmid = {40253504},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Biomarkers ; *Fluorescein Angiography/methods ; *Wet Macular Degeneration/diagnosis/diagnostic imaging ; Prognosis ; },
abstract = {Predictivity of optical coherence tomography (OCT) examination for the development of neovascular age-related macular degeneration (nAMD) was demonstrated to be superior compared to other methods, suggesting it as an elective method for screening purposes. Moreover, OCT and OCT angiography (OCTA) have enabled us to provide accurate prognostic information to nAMD patients. Along with well-known prognostic biomarkers, such as the presence of reticular pseudodrusen, the volume of the pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF) and hyperreflective foci (HRF), emerging parameters show promising results and may allow a further refinement of prediction and customization of treatment and follow up strategies. This review of the literature discusses the main OCT and OCTA biomarkers reported in literature for nAMD, with a special focus on recent updates on the subject. Future perspectives of clinical applications include the development of artificial intelligence models considering all the described biomarkers to allow automatic and detailed characterization of each lesion based on imaging information.},
}
@article {pmid40253438,
year = {2025},
author = {Soundararajan, L and Surendran, H and Patlolla, N and Battu, R and Stoddard, J and Arrizabalaga, S and Liu, Z and Lingam, G and Su, X and Ryals, RC and Pal, R},
title = {Allogeneic RPE cell suspension manufactured at scale demonstrating preclinical safety and efficacy led to IND approval.},
journal = {NPJ Regenerative medicine},
volume = {10},
number = {1},
pages = {19},
pmid = {40253438},
issn = {2057-3995},
abstract = {Cell replacement therapy is a promising therapeutic option for dry age-related macular degeneration (AMD). In this study, we outline our design for scalable manufacture with appropriate quality gates and present in vivo data for establishing preclinical safety and efficacy of an induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) product, thus laying the foundation for Phase 1/2a trial approval in India (ClinicalTrials.gov ID: NCT06394232; date of registration: 23[rd] September 2024). Escalating doses of RPE cell suspension in immunocompromised animals demonstrated absence of tumor formation up to 9 months post-injection. Good Laboratory Practices (GLP) toxicology and tolerability studies in rabbits and non-human primates (NHP) respectively showed no major adverse events. RPE transplanted into immune suppressed RCS rats showed integration, neuroprotection and rescue of visual function. In addition, we provide a detailed description of the modifications in GMP manufacturing protocol to create a final product with a unique composition and Chemistry, Manufacturing and Controls (CMC) studies performed during product development.},
}
@article {pmid40252970,
year = {2025},
author = {Bisen, S and Gogoi, P and Sharma, A and Mukhopadhyay, CS and Singh, NK},
title = {A Disintegrin and Metalloproteinase 10 Regulates Ephrin B2-Mediated Endothelial Cell Sprouting and Ischemic Retinopathy.},
journal = {The American journal of pathology},
volume = {195},
number = {7},
pages = {1311-1327},
pmid = {40252970},
issn = {1525-2191},
support = {P30 EY004068/EY/NEI NIH HHS/United States ; R01 EY029709/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *ADAM10 Protein/metabolism/genetics ; Humans ; *Endothelial Cells/metabolism/pathology ; Mice ; *Ischemia/pathology/metabolism ; *Amyloid Precursor Protein Secretases/metabolism/genetics ; *Membrane Proteins/metabolism/genetics ; *Retinal Neovascularization/pathology/metabolism ; Cell Proliferation ; Cell Movement ; Mice, Inbred C57BL ; Retina/pathology/metabolism ; Retinal Vessels/pathology ; Ephrin-B2 ; },
abstract = {Retinal neovascularization is the leading cause of visual impairment in diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. The extracellular matrix breakdown by metalloproteinase leads to vascular complications in various proliferative retinopathies. A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is involved in physiological angiogenesis. However, limited information exists regarding the role of ADAM10 in proliferative retinopathies. In this study, the levels of active ADAM10 were significantly up-regulated in the ischemic retina, and down-regulation or inactivation of ADAM10 significantly inhibited the proliferation, sprouting, migration, and tube formation of human retinal microvascular endothelial cell. Furthermore, the endothelial cell (EC)-specific deletion of ADAM10 (ADAM10[iΔEC]) significantly attenuated vascular leakage, edema, endothelial cell sprouting, and retinal neovascularization in ischemic retinas of mice exposed to oxygen-induced retinopathy. In experiments investigating the mechanisms through which ADAM10 regulated pathologic angiogenesis, ADAM10 regulated ephrin B2 (EfnB2) expression in endothelial cells. Down-regulation of EfnB2 expression influenced human retinal microvascular endothelial cell proliferation, migration, sprouting, and tube formation. In addition, a significant up-regulation of EfnB2 expression in the ischemic retina was detected. EC-specific depletion of ADAM10 significantly reduced EfnB2 expression, suggesting its involvement in ADAM10-regulated retinal neovascularization. The findings demonstrate how EC-specific ADAM10 regulates pathologic retinal neovascularization in the ischemic retina, indicating its significance as a potential therapeutic target for proliferative retinopathies.},
}
@article {pmid40251762,
year = {2025},
author = {Zhou, WD and Dong, L and Yang, YH and He, Y and Wang, XZ and Zhao, HQ and Zhang, RH and Jonas, JB and Wei, WB},
title = {Aqueous humour concentrations of HB-EGF, EGF and VEGF-A and axial length in humans.},
journal = {Acta ophthalmologica},
volume = {103},
number = {8},
pages = {919-928},
pmid = {40251762},
issn = {1755-3768},
support = {82141128//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82220108017//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82401283//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82141128//The National Natural Science Foundation of China/ ; 82220108017//The National Natural Science Foundation of China/ ; 82401283//The National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Aqueous Humor/metabolism ; Middle Aged ; Male ; Aged ; Female ; *Axial Length, Eye/pathology ; *Vascular Endothelial Growth Factor A/metabolism ; *Epidermal Growth Factor/metabolism ; *Heparin-binding EGF-like Growth Factor/metabolism ; Aged, 80 and over ; Adult ; Biomarkers/metabolism ; },
abstract = {PURPOSE: To investigate relationships between the intraocular concentrations of heparin-binding epidermal growth factor (HB-EGF), epidermal growth factor (EGF) and vascular endothelial growth factor A (VEGF-A) in dependence on axial length in humans.<br><br>DESIGN: Clinical interventional cohort study.<br><br>PARTICIPANTS: Patients with cataract who underwent routine cataract surgery. Inclusion criterion was the absence of any retinal or optic nerve disease except for myopic macular degeneration (MMD) without myopic choroidal neovascularization.<br><br>METHODS: Using a Luminex system, we measured the concentrations of HB-EGF, EGF and VEGF-A in aqueous humour samples taken from patients during cataract surgery.<br><br>MAIN OUTCOME MEASURES: Intracameral concentration of EGF, HB-EGF and VEGF; Axial length.<br><br>RESULTS: The study included 68 patients (age: 61.1&#x2009;&#xb1;&#x2009;11&#x2009;years; range: 44-85&#x2009;years) with a mean axial length of 27.11&#x2009;&#xb1;&#x2009;3.11&#x2009;mm (range: 22.09-35.64&#x2009;mm). The HB-EGF concentration (mean: 3.17&#x2009;&#xb1;&#x2009;0.99&#x2009;pg/mL) increased with longer axial length (&#x3b2;&#x2009;=&#x2009;0.43; p&#x2009;<&#x2009;0.001) and was not associated with age (p&#x2009;=&#x2009;0.10) and intracameral EGF concentration (p&#x2009;=&#x2009;0.22). The EGF concentration (mean: 0.22&#x2009;&#xb1;&#x2009;0.12&#x2009;pg/mL) increased with longer axial length (&#x3b2;&#x2009;=&#x2009;0.35; p&#x2009;=&#x2009;0.004) and higher prevalence of advanced MMD (&#x3b2;&#x2009;=&#x2009;0.35; p&#x2009;=&#x2009;0.008) and was not associated with age (p&#x2009;=&#x2009;0.28) and intracameral VEGF-A concentration (p&#x2009;=&#x2009;0.09). The VEGF-A concentration (mean: 118&#x2009;&#xb1;&#x2009;150&#x2009;pg/mL) decreased with longer axial length (&#x3b2;&#x2009;=&#x2009;-0.54; p&#x2009;<&#x2009;0.001), higher intracameral concentration of HB-EGF (&#x3b2;&#x2009;=&#x2009;-0.26; p&#x2009;=&#x2009;0.03) and lower MMD prevalence (&#x3b2;&#x2009;=&#x2009;-0.31; p&#x2009;=&#x2009;0.02) and was not associated with age (p&#x2009;=&#x2009;0.47) and intracameral EGF concentration (p&#x2009;=&#x2009;0.09).<br><br>CONCLUSIONS: With the concentrations of HB-EGF and EGF increasing with longer axial length, the study supports a potential role of the EGFR signalling pathway activation in human axial myopia. The inverse relationship between VEGF-A concentration and longer axial length agrees with a protective effect of axial myopia against diabetic retinopathy and age-related macular degeneration.},
}
@article {pmid40251333,
year = {2025},
author = {He, Y and Lu, J and Du, Y and Zhao, L and Gong, L and Wu, P and Shu, Q and Peng, H and Wang, X},
title = {Investigation of PANoptosis pathway in age-related macular degeneration triggered by Aβ1-40.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13514},
pmid = {40251333},
issn = {2045-2322},
support = {81670881//National Natural Science Foundation of China/ ; },
mesh = {*Macular Degeneration/metabolism/pathology/chemically induced/genetics ; Animals ; Mice ; Humans ; *Amyloid beta-Peptides/metabolism ; Disease Models, Animal ; *Peptide Fragments/metabolism ; Signal Transduction ; Apoptosis ; Cell Line ; *Necroptosis ; Pyroptosis ; Cytokines/metabolism ; Male ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/metabolism/pathology ; Tomography, Optical Coherence ; Electroretinography ; },
abstract = {Our study aimed to identify PANoptosis in Aβ1-40-induced AMD, both in vivo and in vitro, and to determine if AIM2-PANoptosome mediates this process. We used transcriptomics to explore the signaling pathways and target genes linked to PANoptosis within a mouse model of AMD triggered by Aβ1-40. Optical coherence tomography (OCT), hematoxylin and eosin (H&amp;E) staining, and electroretinography (ERG) were employed to assess retinal damage in terms of morphology and function. Morphological changes in ARPE-19 cells were observed using optical microscopy and scanning electron microscopy. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of cytokines in cell supernatants, mouse orbital serum, and human plasma to evaluate the severity of inflammation. CO-immunoprecipitation(CoIP) and molecular docking were performed to assess the impact and expression of proteins associated with the AIM2-PANoptosome. Quantitative polymerase chain reaction (qPCR), Western blot (WB), immunofluorescence, and apoptosis detection kits were used to evaluate the expression levels of genes and proteins related to PANoptosis-like cell death. Our results showed that the Aβ1-40-induced AMD model had increased expression of apoptosis, necroptosis, and pyroptosis pathways, and AIM2-PANoptosome components. CoIP and docking confirmed increased AIM2, ZBP1, and PYRIN levels under Aβ1-40 treatment. WB and immunofluorescence showed upregulation of PANoptosis-related proteins. Inhibitors reduced Aβ-induced protein expression. ELISA showed increased inflammatory cytokines. Apoptosis assays and microscopy revealed Aβ1-40-induced ARPE-19 cell loss and morphological changes. In conclusion, the Aβ1-40-induced AMD model displayed PANoptosis-like cell death, offering insights into disease pathogenesis.},
}
@article {pmid40251274,
year = {2025},
author = {Schumann, U and Liu, L and Aggio-Bruce, R and Cioanca, AV and Shariev, A and Madigan, MC and Valter, K and Wen, J and Natoli, R},
title = {Spatial transcriptomics reveals regionally altered gene expression that drives retinal degeneration.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {629},
pmid = {40251274},
issn = {2399-3642},
support = {GNT2002239//Department of Health | National Health and Medical Research Council (NHMRC)/ ; GNT2002239//Department of Health | National Health and Medical Research Council (NHMRC)/ ; },
mesh = {Animals ; Mice ; *Transcriptome ; Oxidative Stress ; *Retinal Degeneration/genetics/metabolism/pathology ; *Retina/metabolism ; Mice, Inbred C57BL ; Gene Expression Profiling ; *Gene Expression Regulation ; },
abstract = {Photoreceptor cell death is a hallmark of age-related macular degeneration. Environmental, lifestyle and genetic risk factors are known contributors to disease progression, whilst at the molecular level, oxidative stress and inflammation are central pathogenetic drivers. However, the spatial and cellular origins of these molecular mechanisms remain unclear. We used spatial transcriptomics to investigate the spatio-temporal gene expression changes in the adult mouse retina in response to photo-oxidative stress. We identify regionally distinct transcriptomes, with higher expression of immunity related genes in the superior retina. Exposure to stress induced expression of genes involved in inflammatory processes, innate immune responses, and cytokine production in a highly localised manner. A distinct region ~800 µm superior from the optic nerve head seems a key driver of these molecular changes. Further, we show highly localised early molecular changes in the superior mouse retina during retinal stress and identify novel genes drivers. We provide evidence of angiogenic changes in response to photo-oxidative stress and suggest additional angiogenic signalling pathways within the retina including VEGF, pleiotrophin and midkine. These new insights into retinal angiogenesis pave the way to identify novel drivers of retinal neovascularisation with an opportunity for therapeutic development.},
}
@article {pmid40250716,
year = {2025},
author = {Tan, JK and Steel, DH and Ahmad, S and Viswanathan, A and Mathew, RG and Khaw, PT and Henein, C},
title = {Exploring the potential of rho kinase inhibitors in ophthalmology: From mechanisms to clinical practice.},
journal = {Survey of ophthalmology},
volume = {70},
number = {5},
pages = {900-917},
doi = {10.1016/j.survophthal.2025.03.008},
pmid = {40250716},
issn = {1879-3304},
mesh = {Humans ; *rho-Associated Kinases/antagonists &amp; inhibitors ; *Protein Kinase Inhibitors/therapeutic use ; *Glaucoma/drug therapy ; *Ophthalmology/methods ; },
abstract = {The therapeutic potential of rho kinase (ROCK) inhibitors in ophthalmology is gaining attention, given their multifaceted role in cellular regulation, particularly within ocular pathologies. This review synthesizes findings from clinical and preclinical studies on the efficacy and safety of ROCK inhibitors across glaucoma, corneal, and retinal diseases. We performed a systematic database search in Ovid MEDLINE and Ovid Embase on 5th April 2022 using the following keywords: 'primary open angle glaucoma', 'glaucoma surgery', 'corneal wound healing', 'corneal endothelial dysfunction', 'diabetic retinopathy', 'diabetic macular oedema', 'age-related macular degeneration', 'rho kinase inhibitor', 'rho-kinase inhibitor', rock inhibitor', 'ripasudil', 'netarsudil' and 'fasudil'. Abstracts were screened for relevant studies and results summarized in tables. The analysis of trials done for ROCK inhibitors reveals that they are safe and efficacious drugs, demonstrating noninferiority to existing medical treatments and effective when combined with existing treatments, and are approved for use in treating glaucoma, but not corneal or retinal diseases. Questions remain, however, regarding optimal dosage, patient selection, and cost-effectiveness. ROCK inhibitors demonstrate significant efficacy in reducing intraocular pressure by improving aqueous humour outflow. Additionally, ROCK inhibitors show promise in enhancing endothelial cell migration, thus providing a novel treatment avenue for corneal diseases such as Fuchs endothelial dystrophy. In retinal conditions, including diabetic retinopathy and age-related macular degeneration, ROCK inhibitors reduce vascular permeability, inflammation, and fibrosis, stabilising disease progression.},
}
@article {pmid40250626,
year = {2025},
author = {Chang, RS and Walker, J and Mujeeb, AA and Kadiyala, P and Pisupati, K and Jamison, J and Schwendeman, A and Haggag, Y and Antonetti, DA and Castro, MG and Schwendeman, SP},
title = {Local controlled release of stabilized monoclonal antibodies.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {383},
number = {},
pages = {113743},
doi = {10.1016/j.jconrel.2025.113743},
pmid = {40250626},
issn = {1873-4995},
mesh = {Delayed-Action Preparations/chemistry/administration &amp; dosage ; Animals ; *Antibodies, Monoclonal/administration &amp; dosage/chemistry/therapeutic use ; Humans ; Drug Liberation ; Polylactic Acid-Polyglycolic Acid Copolymer ; Female ; Glioblastoma/drug therapy ; Drug Delivery Systems ; Mice ; },
abstract = {Monoclonal antibody (mAb) therapeutics have become widely successful for treatment of any number of diseases. However, for certain hard-to-reach tissues, e.g., eye, brain, tumors, and joints, local delivery is desired and long-term controlled release is necessary to avoid frequent injections and poor patient compliance. If local and sustained exposure of mAbs (or their Fab or nanobody fragments) could be accomplished by injectable polymer long-acting release (LAR) systems, the incredible potential of mAb therapeutics could be extended to additional diseases, e.g., neovascular age-related macular degeneration (wet AMD) and glioblastoma multiforme (GBM). In prior studies, long-acting delivery of mAbs has been limited by the inability to design a delivery system prepared from a biodegradable polymer used in FDA-approved LARs that achieves long-term continuous release of structurally stable and immunoreactive mAb with a low initial burst release that is easily injectable and avoids material build-up upon repeated injection. Here, we present for the first time a long-acting delivery system capable of delivering several different mAbs for multiple indications by developing a novel process to stabilize mAbs through the combination of formulation, micronization and encapsulation conditions, and to control stabilized mAb exposure in vivo for months by formulation with an appropriate biodegradable polymer (poly(lactic-co-glycolic acid) (PLGA)), utilization of a pH- and pore-modifying agent, and development of a novel PLGA coating layer to control osmotic pressure induced by elevated levels of critical co-encapsulated stabilizers, particularly mAb-stabilizing-trehalose. The resulting implants showed long-term efficacy in animal models for both wet AMD and GBM after single local injections. Although much more work needs to be done before their clinical application to these two diseases, the injectable PLGA platform meets several important benchmarks for controlled mAb delivery and can be developed further for delivery of a wide array of mAbs and other cofactors, offering an improved therapeutic option for treating diseases amenable to local antibody therapy. One Sentence Summary: A generalizable injectable biodegradable PLGA implant platform for site-specific and long-term slow and continuous release of stabilized monoclonal antibody drugs demonstrates improved in vivo efficacy for wet AMD and glioblastoma.},
}
@article {pmid40250423,
year = {2025},
author = {Holleman, AM and Deaton, AM and Hoffing, RA and Krohn, L and LoGerfo, P and Nioi, P and Plekan, ME and Akle Serrano, S and Ticau, S and Walshe, TE and Borodovsky, A and Ward, LD},
title = {Rare predicted loss-of-function and damaging missense variants in CFHR5 associate with protection from age-related macular degeneration.},
journal = {American journal of human genetics},
volume = {112},
number = {5},
pages = {1062-1080},
pmid = {40250423},
issn = {1537-6605},
mesh = {Humans ; *Macular Degeneration/genetics/pathology ; *Mutation, Missense/genetics ; Male ; Female ; Aged ; *Genetic Predisposition to Disease ; *Loss of Function Mutation/genetics ; Complement Factor H/genetics ; Gene Frequency ; Polymorphism, Single Nucleotide/genetics ; Exome Sequencing ; Linkage Disequilibrium ; Middle Aged ; Aged, 80 and over ; *Complement C3b Inactivator Proteins/genetics ; Complement System Proteins ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among older adults worldwide, but treatment options are limited. Genetics studies have implicated the CFH locus, containing CFH and five CFHR genes, CFHR1-5, in AMD. While CFH has been robustly linked with AMD risk, potential additional roles for the CFHR genes remain unclear, obscured by strong linkage disequilibrium across the locus. Investigating rare coding variants can help to identify causal genes in such regions. We used whole-exome sequencing data from 406,952 UK Biobank participants to examine AMD associations with genes at the CFH locus. For each gene, we used burden testing to examine associations of rare (minor-allele frequency [MAF] < 1%) predicted loss-of-function (pLoF) and predicted damaging missense variants with AMD. We considered "broadly defined AMD" (ICD-10 35.3; ncases = 10,700) and "strictly defined AMD" (dry or wet AMD; ncases = 346). Adjusting for CFH-region variants known to independently associate with AMD, we find that CFHR5 rare variant burden significantly associates with a decreased risk of broadly defined AMD (odds ratio [OR] = 0.75, p = 7 × 10[-4]), with this association primarily driven by pLoF variants. Furthermore, the association of CFHR5 rare variants with AMD protection is estimated to be stronger for individuals with the CFH rs1061170 AMD risk allele (p.Tyr402His [p.Y402H]; interaction p = 0.04). Corresponding analyses of strict AMD were underpowered. However, we observe that thinning of the photoreceptor layer outer segment strongly predicts strict AMD and find that CFHR5 rare variant burden is significantly associated with increased thickness of this retinal layer (+0.34 SD, p = 4 × 10[-4], n = 45,365). These findings suggest CFHR5 inhibition as a potential therapeutic approach for AMD.},
}
@article {pmid40249929,
year = {2025},
author = {Thomsen, AK and Steffensen, MA and Villarruel Hinnerskov, JM and Nielsen, AT and Vorum, H and Honoré, B and Nissen, MH and Sørensen, TL},
title = {Plasma Interferon-gamma is Associated with Poor Treatment Response in Neovascular Age-Related Macular Degeneration.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2024.1585},
pmid = {40249929},
issn = {2152-5250},
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in the elderly. Aging is the most important risk factor for AMD, and the aging immune system seems to be involved in pathogenesis. This study investigates the systemic aging immune profile in relation to AMD stage and treatment response. Treatment-naïve patients with neovascular AMD (nAMD), intermediate AMD and healthy controls were included in this prospective study. Participants were examined for systemic aging immune profiles and compared to AMD stage, as well as initial and one-year treatment response in nAMD patients. Flowcytometry was performed to determine T cell differentiation (naïve, central memory and effector memory) and expression of costimulatory markers (CD27, CD28, CD56). Cytokine assays were performed to measure the concentrations of plasma cytokines IFN-γ, IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-27, TNF-α. Polymorphisms of CFH and ARMS2 genes were compared in nAMD patients. Patients with nAMD had significantly higher proportions of central and effector memory CD8+ T cells compared to controls (both P &amp;;lt 0.036). nAMD patients had significantly elevated concentrations of IFN-γ, IL-1β, IL-2, and IL-10 (all P &amp;;lt 0.05). nAMD patients with poor initial treatment response had a significantly higher concentration of plasma IFN-γ compared to good responders (P =0.026). Patients with nAMD had a more advanced systemic aging immune profile with higher levels of T cell differentiation and plasma cytokines compared to controls. Poor initial response had elevated levels of plasma IFN-γ compared to good responders in nAMD.},
}
@article {pmid40249736,
year = {2025},
author = {Sela, A and Levinshtein, R and Shulman, S},
title = {Exposure to air pollutants contributes to increased rate of neovascular age-related macular degeneration in Israel.},
journal = {PloS one},
volume = {20},
number = {4},
pages = {e0317436},
pmid = {40249736},
issn = {1932-6203},
mesh = {Humans ; Israel/epidemiology ; *Macular Degeneration/epidemiology/etiology ; *Air Pollutants/adverse effects/analysis ; Aged ; Female ; Particulate Matter/adverse effects/analysis ; Male ; *Air Pollution/adverse effects ; *Environmental Exposure/adverse effects ; Carbon Monoxide/analysis/adverse effects ; Nitrogen Dioxide/analysis/adverse effects ; Aged, 80 and over ; Ozone/analysis/adverse effects ; Risk Factors ; Middle Aged ; Prevalence ; },
abstract = {Age-related macular degeneration (AMD) is a multi-factorial degenerative disease of the retina and the leading cause for vision loss in the developed world. Air pollution is considered the greatest environmental threat to public health globally. Accumulating evidence indicates that air pollution may be a modifiable risk factor for chronic eye diseases of the lens and retina, including AMD. We examined the concentration of seven air pollution particles and their influence on the prevalence of neovascular AMD in Israel. Records of patients with AMD between 2016 and 2019 were crossed with their residential areas and correlated with pollution data. AMD rates were correlated with 5 types of gas: nitrogen dioxide (NO2), nitrogen oxide (NO), carbon monoxide (CO), ozone (O3), sulphur dioxide (SO2), and particulate matter - PM2.5 and PM10. A total of 93 localities across Israel were included in the analysis. AMD rates were higher in localities with greater air pollution. NO2, NOx, and PM2.5 were positively correlated with AMD rates, while O3 was negatively correlated with AMD rates. However, analysis of the effect of all air pollutant particles combined, showed a complex and highly non-linear effect on AMD rate, with the strongest non-linearity observed for carbon monoxide. NO2, NOx, and PM2.5 contribute to higher rate of AMD in Israel while O3 seems to have a protective role (probably due to ultraviolet filtering) on AMD rates. The interaction between air pollutants and AMD seems to be complex and non-linear and should be further studied.},
}
@article {pmid40249498,
year = {2025},
author = {Beretta, F and Zucchiatti, I and Sacconi, R and Fantaguzzi, F and Lingardo, S and Bandello, F and Querques, G},
title = {Two-Years Real-World Experience of a Tertiary Center with Intravitreal Brolucizumab Switch for Treatment of Exudative Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {6},
pages = {1325-1335},
pmid = {40249498},
issn = {2193-8245},
abstract = {INTRODUCTION: To analyze visual and anatomical outcomes in patients switched to brolucizumab and previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for exudative neovascular age-related macular degeneration (nAMD). These outcomes were was assessed in the real-world setting of a tertiary center with a follow-up period of 2 years.<br><br>METHODS: This retrospective longitudinal study included 29 eyes of 24 patients with exudative nAMD previously treated with at least three injections of another intravitreal anti-VEGF molecule. The eyes were then treated with brolucizumab for at least 24&#xa0;months following the switch. A pro re nata ("as needed") therapeutic regimen was followed in our clinic between January 2021 and June 2024, during which time clinical and anatomical parameters were evaluated, and possible adverse events were recorded.<br><br>RESULTS: After 24&#xa0;months of treatment with brolucizumab, patients showed a significant reduction in central macular thickness (P&#x2009;=&#x2009;0.001) and choroidal thickness (P&#x2009;<&#x2009;0.001). Visual acuity remained stable during the follow-up period. "Poor responders" had longer disease duration and had received more injections before the switch than "good responders." Adverse events included one subretinal hemorrhage and one intraocular inflammation across 302 injections.<br><br>CONCLUSIONS: Treatment with brolucizumab is effective in patients previously treated with other therapeutic molecules. The best outcomes were achieved in patients who switched therapy to brolucizumab early in their disease. Treatment with brolucizumab in this population demonstrated an acceptable risk profile, with only one intraocular inflammatory event out of 302 intravitreal injections.},
}
@article {pmid40247701,
year = {2025},
author = {Parisi, G and Gelormini, F and Vallino, V and Ricardi, F and Marolo, P and Borrelli, E and De Sanctis, U and Reibaldi, M},
title = {Treatment of AMD-related macular neovascularization in a patient with silicone oil tamponade.},
journal = {European journal of ophthalmology},
volume = {35},
number = {5},
pages = {NP59-NP63},
doi = {10.1177/11206721251333273},
pmid = {40247701},
issn = {1724-6016},
mesh = {Humans ; *Silicone Oils/administration &amp; dosage ; Male ; Aged ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Endotamponade/methods ; Vitrectomy/methods ; Ranibizumab ; Tomography, Optical Coherence ; *Wet Macular Degeneration/diagnosis/drug therapy/therapy ; Visual Acuity ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retinal Detachment ; },
abstract = {Purpose: to present a case of active neovascular AMD treated with anti-VEGF drug in the presence of silicone oil. Study design: case report. Results: A 69-year-old male was referred to the surgical retina service due to a sudden loss of peripheral vision in the left eye (LE). Biomicroscopic examination revealed the presence of geographic atrophy in the right eye (RE) and a macula-on retinal detachment in the far periphery with drusen at the posterior pole in LE. Combined OCT-OCTA examination demonstrated the presence of non-active type 1 MNV in the LE. The patient underwent a 25-gauge pars plana vitrectomy (PPV) with silicone oil tamponade in the LE. Post-operative follow-up involved clinical and instrumental monitoring every 7 days for the first 3 months and every 15 days in the fourth month, until the removal of the silicone oil. During the follow-up, we detected the reactivation of type 1 MNV in the LE, and as a result, the patient received three monthly Ranibizumab injections in the LE, in conjunction with the removal of silicone oil from the vitreous cavity at the at the fourth month postoperatively. Conclusions: our case report highlights the clinical response to three injections of intravitreal Ranibizumab therapy in managing active neovascular AMD with SO tamponade. The duration of intravitreal Ranibizumab therapy in SO may not differ significantly compared to an eye with intact vitreous humor.},
}
@article {pmid40247633,
year = {2025},
author = {Viggiano, P and Santoro, M and Boscia, G and Porreca, A and Borrelli, E and Bacherini, D and Lombardi, L and Fumarola, R and Grassi, MO and Termite, AC and Reibaldi, M and Alessio, G and Sadda, S and Boscia, F},
title = {Impact of diabetes and diabetic retinopathy on neovascular exudative age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {103},
number = {6},
pages = {e374-e384},
doi = {10.1111/aos.17502},
pmid = {40247633},
issn = {1755-3768},
mesh = {Humans ; Retrospective Studies ; *Diabetic Retinopathy/complications/diagnosis ; Male ; Female ; *Visual Acuity ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/drug therapy/etiology/complications ; Follow-Up Studies ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography/methods ; Ranibizumab/administration &amp; dosage ; Middle Aged ; Fundus Oculi ; Aged, 80 and over ; },
abstract = {BACKGROUND: To evaluate the functional and morphological changes in patients with nAMD undergoing anti-VEGF therapy, focusing on the impact of concomitant diabetes with or without diabetic retinopathy.<br><br>METHODS: This retrospective cohort study included 1096 eyes from 916 patients with nAMD treated at the retina department of the University of Bari between August 2017 and May 2023. Patients were divided into two groups: 892 eyes without diabetes and 204 eyes with diabetes. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and presence of intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM) and atrophy were assessed at baseline, post-loading phase and at 12-month follow-up.<br><br>RESULTS: At baseline, no significant differences were observed between groups. Post-loading phase, both groups showed significant improvements in BCVA and reductions in CRT. However, SRF persistence was notably more frequent in the diabetic group (64.2% vs. 27.2%, p&#x2009;<&#x2009;0.001). At 12&#x2009;months, SRF was present in 53.7% of the diabetic group compared to 34.9% of the non-diabetic group (p&#x2009;<&#x2009;0.001). Diabetic patients with moderate diabetic retinopathy (DR) exhibited significantly higher SRF persistence compared to those with mild DR or no DR.<br><br>CONCLUSIONS: While anti-VEGF therapy improves visual and anatomical outcomes in both diabetic and non-diabetic patients with nAMD, diabetic patients, particularly those with more severe DR, experience a higher rate of persistence of SRF. This suggests a less than optimal anatomic treatment response and the potential need for more tailored management strategies in this patient population.<br><br>PRECIS: This retrospective cohort study investigated the impact of diabetes mellitus and diabetic retinopathy on neovascular age-related macular degeneration treatment outcomes. The study analysed 1096 eyes from 916 patients undergoing anti-VEGF therapy over 12&#x2009;months.},
}
@article {pmid40247316,
year = {2025},
author = {Zou, R and Cai, J and Chen, T and Mo, W and Qian, H and Zhu, X and Zhang, L},
title = {High-fat diet alters retinal lipid composition and gene expression networks in mice.},
journal = {BMC biology},
volume = {23},
number = {1},
pages = {103},
pmid = {40247316},
issn = {1741-7007},
support = {82301231//National Natural Science Foundation of China/ ; 82071009//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Diet, High-Fat/adverse effects ; Mice ; *Retina/metabolism ; *Lipid Metabolism/genetics ; Mice, Inbred C57BL ; *Gene Regulatory Networks ; Male ; Transcriptome ; },
abstract = {BACKGROUND: High-fat diet (HFD) was suggested to be associated with several retinal diseases, including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Nevertheless, our understanding of the mechanisms governing retinal lipid metabolic homeostasis remains limited, with little attention focused on the influence of HFD on different retinal cell types. To address this gap, we established a high-fat model using mice fed with HFD for a duration of 6 months. Then, we conducted a comparative analysis of the retinal lipidome and proteome between normal diet (ND) and HFD-fed mice to explore the impacts of HFD on retinal lipid metabolism and gene expression network. Furthermore, we also investigated the impacts of HFD on retina in single-cell resolution by single-cell transcriptome sequencing.<br><br>RESULTS: We found that a long-term HFD significantly altered the lipid composition of the retina, with a dramatically elevated cholesterylesters (CE), phosphatidylcholine (PC), and phosphatidylglycerol (PG) level and a decreased eicosanoid level. Proteomic analysis revealed that the primary bile acid biosynthesis pathway was over-activated in HFD retinas. By using single-cell transcriptome analysis, we identified different regulation of gene expression in MG and rod cells in a high-fat environment, whereas the previously identified activation of the bile acid synthesis pathway was predominantly found in MG cells, and may be regulated by alternative pathways of bile acid synthesis, suggesting the critical roles of MG cells in retinal lipid metabolism.<br><br>CONCLUSIONS: Taken together, by multi-omics studies, we unveiled that HFD leading to the development of retinal diseases may be regulated by alternative pathways of bile acid synthesis, and our study will shed light on the treatment of these diseases.},
}
@article {pmid40245427,
year = {2025},
author = {Amon, D and Leisser, C and Schlatter, A and Ruiss, M and Pilwachs, C and Bayer, N and Huemer, J and Findl, O},
title = {Quantification of Metamorphopsia Using a Smartphone-Based Hyperacuity Test in Patients With Idiopathic Epiretinal Membranes: Prospective Observational Study.},
journal = {JMIR perioperative medicine},
volume = {8},
number = {},
pages = {e60959},
pmid = {40245427},
issn = {2561-9128},
mesh = {Humans ; Prospective Studies ; Female ; Male ; *Smartphone ; Aged ; *Epiretinal Membrane/surgery/complications/physiopathology ; Middle Aged ; *Vision Disorders/diagnosis/etiology ; Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; *Vision Tests/methods/instrumentation ; Vitrectomy/methods ; },
abstract = {BACKGROUND: Quality of vision in patients with idiopathic epiretinal membranes (iERMs) is closely linked to distorted vision (metamorphopsia), which is often underestimated in clinical settings. Current surgical decision-making relies heavily on visual acuity and optical coherence tomography findings, which do not adequately reflect the patient's functional vision or the severity of metamorphopsia. There is a clinical need for tools that can reliably quantify this symptom to improve patient outcomes and streamline care pathways.<br><br>OBJECTIVES: This study is the first to assess the use of a novel smartphone-based hyperacuity test (SHT) in quantifying metamorphopsia before and after surgical intervention for iERMs, comparing it with a conventional printed chart.<br><br>METHODS: This prospective observational study included 27 patients with iERMs with symptomatic metamorphopsia detected on the Amsler grid scheduled for vitrectomy with membrane peeling. The SHT (Alleye, Oculocare Medical Inc) and the horizontal (MH) and vertical (MV) M-chart (Inami &amp; Co, Ltd) tests were performed 3 times before and 3 months after surgery. Pre- and postoperative metamorphopsia scores, changes in distance-corrected visual acuity, optical coherence tomography biomarkers, and subjective perception of metamorphopsia were evaluated.<br><br>RESULTS: The mean SHT score significantly (r=0.686; P<.001) improved from 55.2 (SD 18.9) before surgery to 63.5 (SD 16.3) after surgery while the improvement of the M-chart scores were insignificant (MH r=0.37, P=.06; MV r=0.18, P=.36). Pre- and postoperative SHT scores showed very weak and insignificant correlations with the MH, MV, and MH+MV scores. Both metamorphopsia tests showed good reliability (intraclass correlation coefficients >0.75).<br><br>CONCLUSIONS: The SHT showed a significant improvement in postoperative metamorphopsia scores, indicating that it could be a valuable tool for quantifying visual distortion in patients with iERMs. While discrepancies with M-chart results were observed, both tests demonstrated good reliability. Clinically, the SHT may offer a practical solution for monitoring metamorphopsia and guiding complex surgical decision-making, particularly in telemedicine settings. Its accessibility could improve patient management, potentially enhancing preoperative triaging and reducing unnecessary visits.},
}
@article {pmid40243051,
year = {2025},
author = {Ghosh, AK and Chakraborty, D and Sudhalkar, A and Chawla, R and Singh, SR and Sahu, AK and Venkatesh, R and Raval, V and Shah, S and Preetha, P and Bhavsar, M and Patil, S and Khadke, I and Thorat, A},
title = {Safety and effectiveness of brolucizumab in patients with neovascular age-related macular degeneration: A phase IV study from India.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {6},
pages = {826-832},
pmid = {40243051},
issn = {1998-3689},
mesh = {Humans ; Intravitreal Injections ; Male ; Female ; *Visual Acuity ; India/epidemiology ; Prospective Studies ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Aged ; Fluorescein Angiography ; *Wet Macular Degeneration/drug therapy/diagnosis/epidemiology ; Middle Aged ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Follow-Up Studies ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; *Macula Lutea/pathology ; },
abstract = {PURPOSE: The purpose of this study is to evaluate the safety and effectiveness of brolucizumab intravitreal injections (IVI) in Indian patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective, interventional, single-arm, open-label phase IV study included 105 treatment-na&#xef;ve nAMD patients prescribed brolucizumab as per the local prescribing information, across ten centers. The treatment period consisted of 56 weeks, including loading doses at Weeks 0, 4, and 8, followed by disease activity assessment at Week 16, evaluating patients for 12-weekly (q12w) or 8-weekly (q8w) dosing. The primary endpoint was the incidence and characteristics of treatment-emergent adverse events (TEAEs) during 56 weeks. Secondary endpoints included changes in effectiveness variables - visual acuity, intraretinal fluid (IRF), subretinal fluid (SRF), and central subfield thickness (CST), at 16 and 56 weeks.<br><br>RESULTS: Post-Week 16, 74 (70.5%) patients received q12w, and 27 (25.7%) patients received q8w dosing. Four TEAEs were reported in three (2.9%) patients, all ocular: vitritis in two patients who were discontinued and retinal vasculitis and uveitis in one patient who completed the study. No TEAEs were severe, and there were no serious adverse events. Best corrected visual acuity (BCVA) improved significantly by seven letters (95% CI: 5.0, 10.0) at Week 16 and by 15 letters (95% CI: 10.0, 18.0) at Week 56 (P < 0.0001 for both). All anatomical parameters also showed significant reductions over the study period.<br><br>CONCLUSIONS: Brolucizumab 6 mg IVI, given as per the prescribing information, demonstrated a positive benefit/risk profile in Indian patients with nAMD, with no new safety signals.},
}
@article {pmid40242371,
year = {2025},
author = {Chaudhary, V and Guymer, R and Artignan, A and Downey, A and Singh, RP},
title = {Real-World Evidence for Faricimab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Scoping Review.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100744},
pmid = {40242371},
issn = {2666-9145},
abstract = {PURPOSE: Since faricimab (Vabysmo) was approved for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), a growing body of real-world data has been reported, forming an important source of evidence for faricimab in a heterogeneous population. Scoping reviews are an effective approach to comprehensively assess the state of evidence on areas yet to be well characterized, allowing for the inclusion of a wide range of study designs and methodologies. This scoping review aimed to assess the current breadth and nature of real-world evidence (RWE) for faricimab and describe its safety and effectiveness in routine clinical practice.<br><br>DESIGN: Scoping review of published articles and grey literature.<br><br>PARTICIPANTS: Eligible records included primary research reporting on any real-world data from &#x2265;5 participants treated with faricimab in its licensed indications, published in English since 2022. This review did not involve novel data collection in human participants.<br><br>METHODS: MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched on February 16, 2024, and the results were reviewed by 2 independent reviewers. Manual searches of proceedings from major relevant conferences, ClinicalTrials.gov, and bibliographies of relevant systematic literature reviews were also conducted. Findings were summarized descriptively.<br><br>MAIN OUTCOME MEASURES: Data of interest included study design, population characteristics, treatment history, visual function and anatomic outcomes, patient-reported outcomes, safety, and economic outcomes.<br><br>RESULTS: A total of 63 studies reporting RWE for faricimab in patients with nAMD or DME (n&#xa0;=&#xa0;6-12&#xa0;119 eyes) were identified, including a majority of studies in previously treated patients. Studies spanned 10 countries, with a predominance of retrospective observational studies. Results across the majority of studies suggested that faricimab was associated with improved visual acuity, reduced central choroidal/subfield macular thickness, and reduced/resolved retinal fluid and pigment epithelial detachment in both conditions, even over longer study periods (&#x2265;6 months). Adverse events reported were similar to the findings within the registration trials.<br><br>CONCLUSIONS: Outcomes of faricimab in routine practice align with reports from clinical trials, supporting the effectiveness and safety of faricimab in heterogeneous populations. Further high-quality studies using prospective, multicenter designs are required to provide a more comprehensive understanding of the long-term outcomes associated with faricimab.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40241926,
year = {2025},
author = {Ji, PX and Pickel, L and Berger, AR and Sivachandran, N},
title = {Improvement in Dry Age-Related Macular Degeneration with Photobiomodulation.},
journal = {Case reports in ophthalmology},
volume = {16},
number = {1},
pages = {155-162},
pmid = {40241926},
issn = {1663-2699},
abstract = {INTRODUCTION: This case report describes a finding of dramatic improvement in drusen volume and visual acuity in a 73-year-old patient diagnosed with dry age-related macular degeneration (AMD) undergoing daily home photobiomodulation alongside AREDS-2 supplements.<br><br>CASE PRESENTATION: This is a retrospective review of a case presentation from 2023 to 2024. After 8 months of continuous home photobiomodulation, the patient's visual acuity improved from 20/30 to 20/20 in the left eye while the right eye stabilized at 20/25. The outer retina was preserved without signs of geographic atrophy, with a robust reduction in the total number and volume of drusen in both eyes, left greater than right, as shown with optical coherence tomography macular cross-sectional scans.<br><br>CONCLUSIONS: These findings support that photobiomodulation has the potential to improve the management of dry AMD and the overall quality of life, consistent with phase III clinical trials. Future studies are warranted to further establish optimized protocols for broader clinical implementation.},
}
@article {pmid40241463,
year = {2025},
author = {Butler, ETS and Arnold-Vangsted, A and Schou, MG and Anguita, R and Bjerager, J and Borrelli, E and Cehofski, LJ and Ferro Desideri, L and van Dijk, EHC and Faber, C and Grauslund, J and Hajari, JN and Huemer, J and Klefter, ON and Krogh Nielsen, M and Sabaner, MC and Schneider, M and Subhi, Y},
title = {Comparative efficacy of intravitreal anti-VEGF therapy for neovascular age-related macular degeneration: A systematic review with network meta-analysis.},
journal = {Acta ophthalmologica},
volume = {103},
number = {7},
pages = {741-763},
pmid = {40241463},
issn = {1755-3768},
support = {//Velux Fonden/ ; },
mesh = {Humans ; Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Visual Acuity ; Network Meta-Analysis as Topic ; Ranibizumab/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Treatment Outcome ; Recombinant Fusion Proteins/administration &amp; dosage ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; },
abstract = {The aim of this review was to evaluate the comparative efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular AMD. We searched 12 literature databases for randomised clinical trials (RCT) on anti-VEGF therapy for neovascular AMD and extracted data on: change from baseline to 12 months in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and cumulative number of injections at 12 months. The reference for comparison was monthly ranibizumab. Comparisons were made using network meta-analyses. Forty-nine RCTs including 23 257 eyes of 23 257 patients were included. No anti-VEGF drug or treatment regimen provided a better BCVA response compared to the reference. For CRT, small but statistically significant improvements over the reference were observed for brolucizumab 3 mg (-27.9 μm) or 6 mg (-38.1 μm) in loading dose (LD) then every 8-12 weeks, aflibercept 8 mg in LD then every 12 (-26.9 μm) or 16 weeks (-32.1 μm), faricimab 6 mg in LD then treat-and-extend (-18.1 μm) and aflibercept 2 mg in LD then every 8 weeks (-11.3 μm). For the cumulative number of injections, a range of anti-VEGF drugs and treatment regimens provided a statistically significant and clinically meaningful reduction compared to the reference. When results are considered simultaneously, faricimab 6.0 mg or aflibercept 8.0 mg in a treatment regimen with an LD followed by either a treat-and-extend regimen or a fixed 12- or 16-week regimen appears to provide the optimal balance between visual outcomes, anatomical outcomes and the lowest treatment burden. However, studies of the long-term efficacy of newer anti-VEGF drugs are warranted.},
}
@article {pmid40240684,
year = {2025},
author = {Cheung, CMG and Chen, Y and Holz, FG and Tsujikawa, A and Sadda, S},
title = {Geographic atrophy in Asia.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {8},
pages = {2081-2099},
pmid = {40240684},
issn = {1435-702X},
mesh = {Humans ; *Geographic Atrophy/epidemiology/diagnosis ; Asia/epidemiology ; Prevalence ; Tomography, Optical Coherence/methods ; Disease Progression ; Fluorescein Angiography/methods ; *Visual Acuity ; Fundus Oculi ; },
abstract = {PURPOSE: Geographic atrophy (GA) is a late-stage manifestation of age-related macular degeneration associated with vision loss. Differences between Asian and non-Asian populations with GA have been reported. It is essential to understand these differences because they may reflect variations in the natural history of the disease and its underlying pathophysiology, impacting resultant future treatment strategies and clinical trial designs.<br><br>METHODS: A non-systematic search for articles published up to November 22, 2023 was performed using PubMed. Reference lists from included articles were reviewed and relevant articles manually selected and included, as well as read for background information about the topic.&#xa0;Only articles in English were considered for inclusion in this narrative review.<br><br>RESULTS: Although the overall prevalence of GA appears to be low across Asia and shows a male predominance, regional variability is evident. Compared with White and other non-Asian populations, Asian populations typically have more distinct but fewer drusen overall (regardless of type), smaller GA lesion size at presentation, a thicker choroid, and lower rates of bilaterality. In both Asian and non-Asian populations, certain characteristics of GA may be associated with an increased risk of fast disease progression.<br><br>CONCLUSION: The characteristics of GA in Asian populations show some similarities as well as relevant differences compared with those in White and other non-Asian populations. A better understanding of the characteristics associated with GA subphenotypes and predictors of progression will help to optimize management strategies for Asian patients with GA and improve study designs for future interventional trials.},
}
@article {pmid40240124,
year = {2025},
author = {Vu, TA and Fenwick, EK and Man, REK and Thakur, S and Tan, ACS and Cheung, CMG and Gupta, P and Lamoureux, EL},
title = {Vision-related quality of life impact of age-related macular degeneration in older adults aged 60-100 years: a cross-sectional study.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {7},
pages = {822-828},
doi = {10.1136/bjo-2024-325713},
pmid = {40240124},
issn = {1468-2079},
mesh = {Humans ; Cross-Sectional Studies ; *Quality of Life/psychology ; Aged ; Male ; Female ; Middle Aged ; Singapore/epidemiology ; Aged, 80 and over ; *Macular Degeneration/psychology/epidemiology/physiopathology ; Prevalence ; *Visual Acuity/physiology ; Surveys and Questionnaires ; *Vision Disorders/psychology/epidemiology ; },
abstract = {BACKGROUND: We evaluated the prevalence of age-related macular degeneration (AMD) and its interplay with age in influencing vision-related quality of life (VRQoL) in older Asians.<br><br>METHODS: We included 2361 participants aged 60-101 years from the Population Health and Eye Disease Profile in Elderly Singaporeans cross-sectional study (2017-2022). Early and late AMD were graded using the modified Wisconsin grading system. VRQoL was assessed using Rasch-transformed overall, visual functioning and emotional well-being scores of the Brief Impact of Visual Impairment questionnaire. We calculated the prevalence of AMD and used multivariable regression models to assess the associations between AMD and age on VRQoL. VRQoL reduction was deemed clinically meaningful if &#x2265;0.5 SD of the cohort's baseline VRQoL scores.<br><br>RESULTS: The overall prevalence of any, early and late AMD was 6.2%, 4.4% and 1.8%, respectively. The age-specific prevalence increased progressively with age; that is, any AMD (4.1%, 7.2%, 12.9%), early AMD (3.0%, 4.7%, 9.3%) and late AMD (1.1%, 2.5%, 3.5%) across the three age groups (60-79, 70-79 and 80+), respectively. Participants aged &#x2265;80 with late AMD experienced 30.1%, 21.0% and 29.7% poorer overall, visual functioning and emotional well-being, respectively (all p&#x2264;0.001), compared with those aged 60-79 without AMD. Importantly, only those aged &#x2265;80 with late AMD demonstrated both statistically and clinically meaningful VRQoL reductions.<br><br>CONCLUSIONS: AMD is prevalent in ageing Asians and has a substantial impact on visual functioning and emotional well-being. Our findings support early detection of declining visual functioning and mental health and strategies to prevent progression to late-stage AMD in older patients.},
}
@article {pmid40239758,
year = {2025},
author = {Thomas, BB and Rajendran Nair, DS and Rahimian, M and Hassan, AK and Tran, TL and Seiler, MJ},
title = {Animal models for the evaluation of retinal stem cell therapies.},
journal = {Progress in retinal and eye research},
volume = {106},
number = {},
pages = {101356},
pmid = {40239758},
issn = {1873-1635},
support = {P30 EY034070/EY/NEI NIH HHS/United States ; P30 EY029220/EY/NEI NIH HHS/United States ; R01 EY032948/EY/NEI NIH HHS/United States ; R01 EY031834/EY/NEI NIH HHS/United States ; P50 GM076516/GM/NIGMS NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Stem Cell Transplantation/methods ; *Retinal Degeneration/therapy ; *Disease Models, Animal ; Humans ; *Retinal Pigment Epithelium/transplantation/cytology ; Photoreceptor Cells, Vertebrate/transplantation ; },
abstract = {Retinal degeneration (RD) diseases leading to severe vision loss can affect photoreceptors (PRs) that are responsible for phototransduction, or retinal pigmented epithelium (RPE) providing support for PRs. Human pluripotent stem cell (hPSC)-based therapies are a potential approach for restoration of retinal structure in patients with currently incurable RD diseases. Currently, there are two targeted hPSC therapeutics: PR rescue and PR replacement. PR rescue involves the transplantation of RPE or other neural progenitors into the subretinal space to slow down or prevent further RD. RPE transplantation plays a critical role in preserving photoreceptors by providing trophic support and maintaining retinal integrity, particularly in diseases like age-related macular degeneration (AMD). Advances in RPE transplantation methods, such as polarized monolayer cultures and scaffold-based approaches, have shown promise in enhancing graft survival and integration. However, limitations include inconsistent integration, variable neurotrophic factor secretion, and immune rejection risks in non-autologous transplants. In PR replacement, stem cell-derived photoreceptor-like cells or photoreceptor progenitors (PRP) obtained are transplanted into the eye. While PRPs are commonly obtained from retinal organoids (ROs), alternative sources, such as early differentiation stages or direct differentiation protocols, are also utilized to enhance the efficiency and scalability of PRP generation. Challenges include achieving proper integration, forming outer segments, rosette formation, and avoiding immune rejection or tumorigenicity. Various animal models that simulate human RD diseases are being used for establishing surgical feasibility, graft survival and visual functional recovery but fail to replicate clinical immune challenges. Rodent models lack macula-like structures and have limited reliability in detecting subtle functional changes, while larger animal models pose ethical, logistical, and financial challenges. Immunocompromised models have been developed for minimizing xenograft issues. Visual functional testing for efficacy includes optokinetic testing (OKN), electroretinography (ERG), and electrophysiological recordings from the retina and brain. These tests often fail to capture the complexity of human visual recovery, highlighting the need for advanced models and improved functional testing techniques. This review aims to aggregate current knowledge about approaches to stem cell transplantation, requirements of animal models chosen for validating vision benefits of transplantation studies, advantages of using specific disease models and their limitations. While promising strides have been made, addressing these limitations remains essential for translating stem cell-based therapies into clinical success.},
}
@article {pmid40239664,
year = {2025},
author = {Rizzato, A and Giannakaki-Zimmermann, H and Weisskopf, F and Hatz-Wurziger, K},
title = {Microvascular Abnormalities, Inner Retina Thinning and Sectorial Optic Atrophy after Low-dose Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration: A Case Report.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {4},
pages = {421-425},
pmid = {40239664},
issn = {1439-3999},
}
@article {pmid40239176,
year = {2025},
author = {Asiamah, R and Ampo, E and Ampiah, EE and Nketia, MO and Kyei, S},
title = {Impact of smoking on ocular health: A systematic review and meta-meta-analysis.},
journal = {European journal of ophthalmology},
volume = {35},
number = {4},
pages = {1506-1518},
doi = {10.1177/11206721251334705},
pmid = {40239176},
issn = {1724-6016},
mesh = {Humans ; *Eye Diseases/epidemiology/etiology ; Global Health ; Risk Factors ; *Smoking/adverse effects ; },
abstract = {PurposeTo provide a comprehensive synthesis of the available evidence on the effects of smoking on ocular health.MethodsDatabases (PubMed, SCOPUS, Web of Science) were searched through December 2024 for systematic reviews and meta-analyses on smoking and ocular disease risk. Meta-analysis quality was assessed using the 16-item A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2.ResultsSixteen studies were included, with 12 qualifying for meta-meta-analysis. Current smokers are 7 to 12 times more likely to develop AMD than non-smokers (Odds Ratio [OR]: 11.93 [95% CI 4.40 to 32.33]; Risk Ratio [RR]: 7.45 [95% CI 4.09 to 13.57]). Past smokers have a seven-fold increased risk (OR: 7.09 [95% CI 4.79 to10.51]). For POAG, current smokers have three times the risk (OR: 3.07 [95% CI 2.07 to 4.54]), and past smokers have three times the risk (OR: 2.64 [95% CI 2.33 to 3.00]). Current smokers are four times more likely to develop cataracts (OR: 4.15 [95% CI 3.35 to 5.15]), while "ever" smokers face a six-fold risk (OR: 5.96 [95% CI 3.21 to 11.04]).ConclusionSmoking is a modifiable risk factor for numerous ocular diseases. Public health efforts and clinical guidelines should emphasize smoking cessation to reduce smoking-related ocular disease incidence and promote ocular health.},
}
@article {pmid40236073,
year = {2025},
author = {Jensen, N and Goldstein, AK and Ly, K and Devaud, Q and Palanker, D},
title = {Maximizing the fidelity of a photovoltaic subretinal prosthesis for human patients.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.03.31.646451},
pmid = {40236073},
issn = {2692-8205},
abstract = {OBJECTIVE: PRIMA subretinal implants provide prosthetic vision in patients blinded by age-related macular degeneration, with acuity closely matching the sampling limit of the pixel pitch: a single 100 µm pixel per line of a letter corresponds to 20/420 acuity. Decreasing the pixel size in the same flat geometry is difficult due to the constrained electric field, especially considering a 40 µm thick debris layer separating the implant from the target neurons. Here we optimize the electrode design to help overcome such limitations.<br><br>APPROACH: An end-to-end modeling pipeline combines the subretinal photovoltaic implant simulator (RPSim) based on the Xyce circuit simulator with an interface to COMSOL Multiphysics for electric field modelling. It was used to generate and characterize implants in an open-loop sampling-based optimization. Implant performance was evaluated with respect to voltage drop across bipolar cells (representing the stimulation strength), pattern contrast, and neural selectivity.<br><br>MAIN RESULTS: The highest selectivity in stimulation of bipolar cells was achieved with arrays having active electrodes on pillars and return electrodes connected in a mesh surrounding the photovoltaic pixels in the array. Such a design with pixel size down to 20 &#xb5;m provides stimulation strength exceeding, and contrast similar to that of flat 100 &#xb5;m PRIMA pixels.<br><br>SIGNIFICANCE: Using a novel 3-D electrode design, the pitch of the photovoltaic array can be decreased to 20 &#xb5;m, while providing performance that exceeds the flat 100 &#xb5;m PRIMA pixels. In humans, 20 &#xb5;m resolution on the retina corresponds to a visual acuity of 20/80 - a five times improvement compared to the current clinical device.},
}
@article {pmid40235808,
year = {2025},
author = {He, Q and Zhang, Y and Shen, M and Gregori, G and Rosenfeld, PJ and Wang, RK},
title = {Choroidal thinning can be assessed through facial video analysis.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {4},
pages = {2671-2681},
pmid = {40235808},
issn = {2223-4292},
abstract = {BACKGROUND: Different features of skin are associated with various medical conditions and provide opportunities to evaluate and monitor body health. This study created a strategy to assess choroidal thinning through the video analysis of facial skin.<br><br>METHODS: Videos capturing the entire facial skin were collected from 48 participants with age-related macular degeneration (AMD) and 12 healthy individuals. These facial videos were analyzed using video-based trans-angiosomes imaging photoplethysmography (TaiPPG) to generate facial imaging biomarkers that were correlated with choroidal thickness (CT) measurements. The CT of all patients was determined using swept-source optical coherence tomography (SS-OCT).<br><br>RESULTS: The results revealed the relationship between relative blood pulsation amplitude (BPA) in three typical facial angiosomes (cheek, side-forehead, and mid-forehead) and the average macular CT (r=0.48, P<0.001; r=-0.56, P<0.001; r=-0.40, P<0.01). When considering a diagnostic threshold of 200 &#xb5;m for CT, the newly developed facial video analysis tool effectively distinguished between cases of choroidal thinning and normal cases, yielding areas under the curve of 0.75, 0.79, and 0.69.<br><br>CONCLUSIONS: These findings shed light on the connection between choroidal blood flow and facial skin hemodynamics, which suggests the potential for predicting vascular diseases through widely accessible skin imaging data.},
}
@article {pmid40235102,
year = {2025},
author = {Kim, MA and Choi, SI and Kim, JM and Oh, HS and You, YS and Lee, WK and Kim, SH and Kwon, OW and Kim, JY},
title = {Reinjection in Patients with Intraocular Inflammation Development after Intravitreal Brolucizumab Injection.},
journal = {Korean journal of ophthalmology : KJO},
volume = {39},
number = {3},
pages = {213-221},
pmid = {40235102},
issn = {2092-9382},
mesh = {Humans ; Intravitreal Injections/adverse effects ; Retrospective Studies ; Male ; Female ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Middle Aged ; Aged ; Follow-Up Studies ; *Visual Acuity ; *Endophthalmitis/chemically induced/diagnosis/drug therapy/epidemiology ; Tomography, Optical Coherence ; Incidence ; Recurrence ; Fundus Oculi ; },
abstract = {PURPOSE: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development.<br><br>METHODS: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development.<br><br>RESULTS: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 &#xb1; 16.73 days, with 15 cases developing IOI within 1 week.<br><br>CONCLUSIONS: This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.},
}
@article {pmid40234595,
year = {2025},
author = {Stanescu, N and Khalifa, K and Arnon, R and Rabina, G and Nemet, AY and Arbel, I and Geffen, N and Segal, O},
title = {The association between optical density ratio of intraretinal fluid and visual acuity in neovascular age related macular degeneration after 36 months of follow up.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {2031-2035},
pmid = {40234595},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Aged ; Follow-Up Studies ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Subretinal Fluid/diagnostic imaging ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Aged, 80 and over ; Ranibizumab/therapeutic use ; Prognosis ; Middle Aged ; Fluorescein Angiography ; },
abstract = {OBJECTIVE: To investigate the prognostic significance of optical density ratio (ODR) of intraretinal fluid (IRF) on best corrected visual acuity (deltaBCVA) in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents.<br><br>METHODS: In this retrospective study, optical coherence tomography (OCT) scans of treatment-na&#xef;ve eyes with nAMD treated with anti-VEGF injections were reviewed. ODR of retinal fluid compartments was calculated using strict and flexible methods in each OCT image. We used linear mixed models to investigate the relationship between ODR values on OCT and deltaBCVA after 36 months of follow up.<br><br>RESULTS: We included 86 eyes of 78 patients. We found negative associations between strict ODR of IRF (p&#x2009;=&#x2009;0.02; coef. -0.05, 95% CI -0.10, -0.01), and flexible ODR of IRF (p&#x2009;=&#x2009;0.03; coef. -0.05, 95% CI -0.10, -0.01), and deltaBCVA after 36 months. ODR of SRF and PED were not significantly associated with deltaBCVA.<br><br>CONCLUSION: This is the largest study to investigate the relationship between ODR in nAMD patients and deltaBCVA. Eyes with higher ODR values of IRF are less likely to have a deterioration in BCVA over 36 months of follow up. ODR could be used as another OCT prognostic biomarker for BCVA in nAMD patients.},
}
@article {pmid40234594,
year = {2025},
author = {Wang, H and Ie, A and Chan, T and Yates, W and Kalloniatis, M and Tong, J and Zhang, S and Phan, T and Go, C and Phu, J},
title = {ChatGPT-4 for addressing patient-centred frequently asked questions in age-related macular degeneration clinical practice.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {2023-2030},
pmid = {40234594},
issn = {1476-5454},
support = {1186915//Department of Health | National Health and Medical Research Council (NHMRC)/ ; },
mesh = {Humans ; *Macular Degeneration/diagnosis/therapy ; *Patient-Centered Care ; Surveys and Questionnaires ; *Ophthalmology ; Female ; Generative Artificial Intelligence ; },
abstract = {PURPOSE: Large language models have shown promise in answering questions related to medical conditions. This study evaluated the responses of ChatGPT-4 in answering patient-centred frequently asked questions (FAQs) relevant in age-related macular degeneration (AMD).<br><br>METHODS: Ten experts across a range of clinical, education and research practices in optometry and ophthalmology. Over 200 patient-centric FAQs from authoritative professional society, hospital and advocacy websites were condensed into 37 questions across four themes: definition, causes and risk factors, symptoms and detection, and treatment and follow-up. The questions were individually input into ChatGPT-4 to generate responses. The responses were graded by the experts individually using a 5-point Likert scale (1&#x2009;=&#x2009;strongly disagree; 5&#x2009;=&#x2009;strongly agree) across four domains: coherency, factuality, comprehensiveness, and safety.<br><br>RESULTS: Across all themes and domains, median scores were all 4 ("agree"). Comprehensiveness had the lowest scores across domains (mean 3.8&#x2009;&#xb1;&#x2009;0.8), followed by factuality (mean 3.9&#x2009;&#xb1;&#x2009;0.8), safety (mean 4.1&#x2009;&#xb1;&#x2009;0.8) and coherency (mean 4.3&#x2009;&#xb1;&#x2009;0.7). Examination of the individual 37 questions showed that 5 (14%), 21 (57%), 23 (62%) and 9 (24%) of the questions had average scores below 4 (below "agree") for the coherency, factuality, comprehensiveness and safety domains, respectively. Free-text comments highlighted issues related to superseded or older technologies, and techniques that are not routinely used in clinical practice, such as genetic testing.<br><br>CONCLUSIONS: ChatGPT-4 responses to FAQs in AMD were generally agreeable in terms of coherency, factuality, comprehensiveness, and safety. However, areas of weakness were identified, precluding recommendations for routine use to provide patients with tailored counselling in AMD.},
}
@article {pmid40234500,
year = {2025},
author = {Hansman, DS and Lim, K and Thomas, D and Casson, RJ and Peet, DJ},
title = {Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13012},
pmid = {40234500},
issn = {2045-2322},
support = {1099932//National Health and Medical Research Council of Australia/ ; 6619-21//The Leukemia Foundation/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Macular Degeneration/metabolism/pathology ; Humans ; *Cytokines/metabolism/pharmacology ; *Metabolome ; Animals ; Rats ; Cell Line ; Metabolomics/methods ; },
abstract = {Age-related macular degeneration (AMD) is associated with chronic inflammation of the retinal pigment epithelium (RPE) and elevated cytokines including TNFα, TGF-β, IL-6, and IL-1β. As a metabolic intermediary supporting aerobic glycolysis in the adjacent photoreceptors, the RPE's metabolic responses to inflammation and the optimal methods to study cytokine-driven metabolic programming remain unclear. We performed a rigorous comparison of ARPE-19 cells and rat eyecup metabolomes, revealing key distinctions. Rat eyecups exhibit higher levels of lactate and palmitate but depleted glutathione and high-energy nucleotides. Conversely, ARPE-19 cells are enriched with high-energy currency metabolites and the membrane phospholipid precursors phosphocholine and inositol. Both models showed contrasting responses to individual cytokines: ARPE-19 cells were more sensitive to TNFα, while eyecups responded more strongly to TGF-β2. Notably, a combined cytokine cocktail elicited stronger metabolic effects on ARPE-19 cells, more potently impacting both metabolite abundance (41 vs. 29) and glucose carbon flux (29 vs. 5), and influencing key RPE metabolites such as alanine, glycine, aspartate, proline, citrate, α-ketoglutarate, and palmitate. Overall, these findings position ARPE-19 cells as a more responsive platform for studying inflammatory cytokine effects on RPE metabolism and reveal critical RPE metabolites which may be linked with AMD pathogenesis.},
}
@article {pmid40233906,
year = {2025},
author = {Kaith, A and Garg, U and Jain, N and Pandey, M and Kaul, S and Gorain, B and Amin, MCIM},
title = {Pullulan as a sustained release carrier for ocular drug delivery: a review.},
journal = {International journal of biological macromolecules},
volume = {309},
number = {Pt 4},
pages = {143146},
doi = {10.1016/j.ijbiomac.2025.143146},
pmid = {40233906},
issn = {1879-0003},
mesh = {*Glucans/chemistry/therapeutic use ; Humans ; *Delayed-Action Preparations/chemistry ; *Drug Carriers/chemistry ; Animals ; *Drug Delivery Systems ; Drug Liberation ; Administration, Ophthalmic ; *Eye Diseases/drug therapy ; },
abstract = {Pullulan, an exopolysaccharide, obtained from the fungus Aureobasidium pullulans, is a non-ionic, hydrophilic, biodegradable, biocompatible, and tolerogenic polymers that is used for the formulation of bioconjugates in the therapeutic delivery to target different cells and tissues. It is known to possess outstanding film-casting qualities and can produce a clear and biodegradable film. Furthermore, appropriate derivatizing pullulan provides active surfaces that facilitate binding with active pharmaceutical ingredients to the polymer backbone to produce micro/nanoparticulate systems for controlled or sustained drug release. Ophthalmic problems like glaucoma, age-related macular degeneration, and cataracts are very prevalent across the globe, and their treatment options mainly include conventional topical solutions and gels, which possess very low drug-contact time and poor bioavailability, leading to frequent dosing and patient incompliance. Sustained release dosage forms like ocuserts, ocular films, and in-situ gels can help in achieving the intended therapeutic outcomes for an extended duration by minimizing the number of doses. Here, we present a comprehensive critical review of the utilization and application of pullulan, together with its derivatives, to combat problems with ocular medication administration. This article also provides insight for further research on this topic to utilize its advantages to the fullest in the future for improved delivery of therapeutics in the treatment of ocular disorders.},
}
@article {pmid40233699,
year = {2025},
author = {Hsu, ST and Chen, LJ and Chan, WC and Lai, YJ and Chiu, FY and Chiu, N and Tsai, HL},
title = {Long-Term retrospective analysis of retinal pigment epithelium atrophy and secondary hyperplasia following verteporfin photodynamic therapy.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {53},
number = {},
pages = {104576},
doi = {10.1016/j.pdpdt.2025.104576},
pmid = {40233699},
issn = {1873-1597},
mesh = {Humans ; *Photochemotherapy/adverse effects/methods ; *Verteporfin/adverse effects/therapeutic use ; Retrospective Studies ; *Retinal Pigment Epithelium/pathology/drug effects ; Female ; Male ; Middle Aged ; *Photosensitizing Agents/adverse effects/therapeutic use ; Atrophy/chemically induced ; Adult ; Hyperplasia/chemically induced ; Choroidal Neovascularization/drug therapy ; Visual Acuity/drug effects ; Aged ; Central Serous Chorioretinopathy/drug therapy ; Risk Factors ; Wet Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: To identify risk factors for retinal pigment epithelium (RPE) atrophy associated with verteporfin photodynamic therapy (PDT), with or without secondary RPE hyperplasia, and to evaluate long-term visual outcomes.<br><br>MATERIALS AND METHODS: This retrospective study analyzed 197 eyes of 180 patients who underwent verteporfin PDT between 2000 and 2023. Baseline demographic and clinical characteristics were evaluated.<br><br>RESULTS: Among 197 eyes that underwent one or more sessions of PDT, PDT-induced RPE atrophy was observed in 2 eyes (2.4 %) with wet age-related macular degeneration (wet AMD) or polypoidal choroidal vasculopathy (PCV) and in 1 eye (3.8 %) with central serous chorioretinopathy (CSC). In contrast, 18 eyes (22.2 %) with myopic choroidal neovascularization (mCNV) developed PDT-induced RPE atrophy. Subgroup analysis revealed that in the mCNV group, patients with PDT-induced RPE atrophy were significantly younger (36.5 &#xb1; 13.7 years vs. 46.3 &#xb1; 12.8 years; P < 0.001) and underwent more PDT sessions (2.6 &#xb1; 1.8 vs. 1.5 &#xb1; 0.8; P < 0.001) than those without atrophy. Five patients developed secondary RPE hyperplasia, all from the mCNV group.<br><br>CONCLUSION: Verteporfin PDT rarely induces RPE atrophy in patients with wet AMD, PCV, and CSC. However, in patients with myopic CNV, PDT may occasionally cause alterations in the RPE, including both atrophy and secondary hyperplasia. While PDT-induced RPE atrophy was not a statistically significant predictor of best-corrected visual acuity at the final follow-up in the mCNV and wet AMD/PCV groups in the linear regression analysis, it was a significant factor in the CSC group.},
}
@article {pmid40233664,
year = {2025},
author = {Okonkwo, ON and Hassan, AO and Ajiboye, I and Onunwa, OZ and Oyekunle, I},
title = {Intravitreal injection of faricimab to treat macular and retinovascular diseases in Nigerians: Early real-world experience.},
journal = {Journal francais d'ophtalmologie},
volume = {48},
number = {6},
pages = {104516},
doi = {10.1016/j.jfo.2025.104516},
pmid = {40233664},
issn = {1773-0597},
mesh = {Humans ; Intravitreal Injections ; Male ; Female ; Retrospective Studies ; Aged ; Middle Aged ; Aged, 80 and over ; Nigeria/epidemiology ; Visual Acuity/drug effects ; Treatment Outcome ; Diabetic Retinopathy/drug therapy/epidemiology ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Macular Edema/drug therapy/epidemiology ; *Retinal Diseases/drug therapy/epidemiology ; Wet Macular Degeneration/drug therapy/epidemiology ; Macular Degeneration/drug therapy/epidemiology ; West African People ; Antibodies, Bispecific ; },
abstract = {INTRODUCTION: Faricimab is a novel bispecific antibody for treating retinovascular diseases. Nigerians were not included in the pivotal approval studies; therefore, its performance in Nigerians is unknown.<br><br>PURPOSE: To report indications, outcomes and safety of intravitreal faricimab (IVF) in Nigerians.<br><br>STUDY SETTING: Single tertiary care ophthalmology hospital.<br><br>MATERIAL AND METHODS: Retrospective review of eyes documented to have received at least one IVF injection from January to August 2024, with no exclusions. Information retrieved from case records includes patient demographics, indication, previous intravitreal injections, number of IVF injections, visual outcome and central subfield thickness (CST), before and after IVF injection.<br><br>RESULTS: A total of 77 IVF injections were administered to 39 eyes of 31 patients; mean age 65.69 years (&#xb1;10), ranging from 48 to 80 years. Fifteen were male (17 eyes), and 16 were female (22 eyes). The most common indications for treatment were neovascular age-related macular degeneration (nAMD) in 13 eyes (33%) and diabetic macular edema (DME) in 10 eyes (25.6%). For all eyes, visual acuity improved from a baseline LogMAR score of 0.90 (&#xb1;0.57) to 0.88 (&#xb1;0.64) after the first injection, and 0.74 (&#xb1;0.61) after the final injection. Central subfield thickness (CST) decreased from 403.80 microns (&#xb1;208.61) to 303 microns (&#xb1;191.07). In treatment-na&#xef;ve eyes (n=19), vision improved from a LogMAR score of 0.87 (&#xb1;0.55) to 0.66 (&#xb1;0.45) after the final injection (P=0.006), and CST decreased from 433.94 microns (&#xb1;258.58) to 310.45 microns (&#xb1;206.48) (P=0.010). In previously treated (switch) eyes (n=20), visual acuity improved from 0.91 (&#xb1;0.60) to 0.81 (&#xb1;0.74) (P=0.019), and CST decreased from 376 microns (&#xb1;153.48) to 297.53 microns (&#xb1;186.19) (P=0.004). There were no adverse reactions reported following the injections.<br><br>CONCLUSION: IVF was safe and effective for treating nAMD, DME and other retinovascular diseases in Nigerians in this pilot study. Outcomes of large sample size studies are expected.},
}
@article {pmid40233131,
year = {2025},
author = {Brinkmeier, ML and Wang, SQ and Pittman, HA and Cheung, LY and Prasov, L},
title = {Myelin regulatory factor (MYRF) is a critical early regulator of retinal pigment epithelial development.},
journal = {PLoS genetics},
volume = {21},
number = {4},
pages = {e1011670},
pmid = {40233131},
issn = {1553-7404},
support = {K08 EY032098/EY/NEI NIH HHS/United States ; P30 EY007003/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism/growth &amp; development ; Animals ; Mice ; Humans ; Mice, Knockout ; PAX6 Transcription Factor/genetics ; Cell Differentiation/genetics ; Gene Expression Regulation, Developmental ; Signal Transduction ; SOXE Transcription Factors/genetics/metabolism ; *Transcription Factors/genetics/metabolism ; Microphthalmia-Associated Transcription Factor/genetics ; Macular Degeneration/genetics/pathology ; },
abstract = {Myelin regulatory factor (Myrf) is a critical transcription factor in early retinal and retinal pigment epithelial development, and human variants in MYRF are a cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed on Myrf conditional knockout mice (Rx > Cre Myrffl/fl) at 3 developmental timepoints. Myrf was expressed specifically in the RPE, and expression was abrogated in Rx > Cre Myrffl/fl eyes. scRNAseq analysis revealed a loss of RPE cells at all timepoints resulting from cell death. GO-term analysis in the RPE revealed downregulation of melanogenesis and anatomic structure morphogenesis pathways, which were supported by electron microscopy and histologic analysis. Novel structural target genes including Ermn and Upk3b, along with macular degeneration and inherited retinal disease genes were identified as downregulated, and a strong upregulation of TGFß/BMP signaling and effectors was observed. Regulon analysis placed Myrf downstream or parallel to Pax6 and Mitf and upstream of Sox10 in RPE differentiation. Together, these results suggest a strong role for MYRF in the RPE maturation by regulating melanogenesis, cell survival, and cell structure, in part acting through suppression of TGFß signaling and activation of Sox10.},
}
@article {pmid40232637,
year = {2025},
author = {Shellvarajah, M and Nguyen, V and Steinmann, S and Gillies, MC and Sagkriotis, A and Barthelmes, D},
title = {Adherence to Anti-VEGF Treatment in Patients with Neovascular Age-Related Macular Degeneration: A Real-World Study.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {6},
pages = {1261-1269},
pmid = {40232637},
issn = {2193-8245},
abstract = {INTRODUCTION: The evolution of treatment patterns in neovascular age-related macular degeneration (nAMD) warrants investigation into the impact of patients' adherence to anti-vascular endothelial growth factor (VEGF) treatment on visual outcomes. This retrospective, non-randomized, non-comparative study aimed to investigate real-world adherence to anti-VEGF treatment.<br><br>METHODS: Patient (eyes) (&#x2265;&#x2009;50 years) with a diagnosis of nAMD who had a first injection of aflibercept or ranibizumab between January 2016 and December 2018 and 12 months of follow-up were included. Visual acuity (VA; logMAR letters) and duration of injection intervals were recorded. Adherence was defined as&#x2009;<&#x2009;20% of visits deviating from the schedule by&#x2009;&#x2265;&#x2009;14 days.<br><br>RESULTS: Overall, 133 patient eyes were included: 129 adherent, and four non-adherent. Mean (standard deviation) baseline VA was 57.0 (23.6) and 53.8 (35.3) letters in adherent and non-adherent patient eyes, respectively. Mean change in VA by month 12 was higher in adherent (6.3 letters) than non-adherent patient eyes (-&#x2009;11 letters). Compared with the previous visit, adherent visits were associated with a mean increase in VA of 0.67 letters and non-adherent visits with a decrease of 2.30 letters.<br><br>CONCLUSIONS: These results emphasize the importance of adherence to appropriate dosing regimens to optimize visual outcomes in patients with nAMD.},
}
@article {pmid40232477,
year = {2025},
author = {Shahidul Islam, M and Song, J and Chen, A and Mammo, Z and Jin Ju, M},
title = {Effective interscan time for enhanced in vivo choriocapillaris imaging with OCT angiography.},
journal = {Optics letters},
volume = {50},
number = {8},
pages = {2711-2714},
doi = {10.1364/OL.557992},
pmid = {40232477},
issn = {1539-4794},
mesh = {*Tomography, Optical Coherence/methods ; *Choroid/diagnostic imaging/blood supply ; *Angiography/methods ; Humans ; Time Factors ; Fluorescein Angiography ; },
abstract = {Despite advancements in optical coherence tomography angiography (OCTA), in vivo imaging of the choriocapillaris (CC) remains challenging due to its dense microvascular structure and low reflectivity. While previous studies have explored various scanning protocols to enhance CC visualization, most approaches rely on oversampling, beam size adjustments, large numbers of repetitive B-scans (BM), and volume registration. However, interscan time-a critical parameter that influences flow contrast and vascular detail-has been largely overlooked. In this Letter, we introduce interscan time as a novel, to the best of our knowledge, CC imaging parameter and propose an optimized OCTA protocol by leveraging a 1.6 MHz FDML swept-source laser and step-bidirectional scanning method to investigate its impact across beam sizes and BM-scans. Our findings reveal that shorter interscan time significantly improves CC visualization by enhancing vessel contrast and preserving microvascular details, enabling better clinical assessment of retinal diseases such as age-related macular degeneration and diabetic retinopathy.},
}
@article {pmid40232257,
year = {2025},
author = {Laurinaviciute, G and Jakimaviciene, EM and Simkunaite-Rizgeliene, R and Galgauskas, S and Cepuliene, R and Tutkuviene, J},
title = {Visual acuity and eye parameters in relation to body size, shape and composition, considering maternal undernutrition during pregnancy.},
journal = {Homo : internationale Zeitschrift fur die vergleichende Forschung am Menschen},
volume = {},
number = {},
pages = {},
doi = {10.1127/homo/2025/1906},
pmid = {40232257},
issn = {1618-1301},
abstract = {The purpose of our study was to examine the eye parameters in relation to body size, proportions and composition in healthy or age-related macular degeneration affected adults, considering maternal diet during pregnancy. Statistically significant smaller corneal radius was found in maternal undernutrition groups comparing with maternal normal nutrition groups (p < 0.05), but there was no significant difference in retinal parameters or vision (p > 0.05). Statistically significant smaller distal width of humerus and Frame index in both genders, shorter humerus, radius, femur and tibia length in males, lower height, sitting height and shorter fourth finger length in females was found in age-related macular degeneration maternal undernutrition group compared to healthy retina normal nutrition group (p < 0.05). Our study revealed that participants with higher stature, longer limbs, more robust skeleton and higher accumulation of fat on trunk as well as with higher absolute active mass had statistically significant lower chance to suffer from age-related macular degeneration (OR < 1.0; p < 0.05). Subjects which suffered from maternal undernutrition had steeper central corneal radius, but no clear changes in the retinal thickness, which determines maintenance of good visual acuity. Developmental programming theory was supported by anthropometric peculiarities of individuals with age-related macular degeneration in the maternal undernutrition group subjects had smaller distal width of humerus and Frame index, males had shorter humerus, radius, femur and tibia and women had shorter fourth fingers. Taller subjects with longer limbs, higher Frame index, more abundant fat accumulation on trunk, higher absolute active mass had lower chance to suffer from age-related macular degeneration.},
}
@article {pmid40231247,
year = {2025},
author = {Reddy, A and Greene, C and Hashimoto, Y and Kiang, AS and Hudson, N and Adamson, P and Santos-Ferreira, T and Campbell, M},
title = {Enhanced retinal pigment epithelial cells as a delivery vehicle for retinal disease.},
journal = {Molecular therapy. Methods &amp; clinical development},
volume = {33},
number = {2},
pages = {101450},
pmid = {40231247},
issn = {2329-0501},
abstract = {Age-related macular degeneration (AMD) represents a major global health burden, with current estimates suggesting that up to 200 million people are affected globally. While effective treatments exist for the exudative form of the disease termed choroidal neovascular AMD, there remain challenges associated with long-term responses to treatment and the ongoing parallel development of the non-exudative form of AMD. Here, we sought to develop an approach for long-term delivery of both aflibercept, a decoy receptor that neutralises vascular endothelial growth factor and a concomitant treatment focused on treating the non-exudative form of AMD. To this end, we developed a series of induced pluripotent stem cell (iPS)-derived retinal pigment epithelial (RPE) cell lines that stably expressed aflibercept and/or sCD59. These cell lines were shown to produce high concentrations of both proteins. Sub-retinal injection of enhanced RPE cells potently prevented leakage of neovascular lesions in the JR5558 mouse model of retinal and choroidal neovascularization. Early results described here suggest that enhanced iPS-derived RPE cells could represent a novel approach to the long-term delivery of therapeutic agents to the eye.},
}
@article {pmid40230880,
year = {2025},
author = {Huh, MD and Le, SN and O'Brien, KS and Keenan, JD and Stewart, JM},
title = {Potential Efficacy of Metformin for Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100741},
pmid = {40230880},
issn = {2666-9145},
abstract = {TOPIC: Metformin, a widely used diabetes medication, has shown potential for treating age-related macular degeneration (AMD) due to its antioxidative, anti-inflammatory, and antiangiogenic properties. This study aims to systematically review and analyze the efficacy of metformin in reducing AMD prevalence.<br><br>CLINICAL RELEVANCE: Metformin's potential to serve as a treatment for AMD could significantly reduce the burden of vision loss, offering a cost-effective and widely accessible solution.<br><br>METHODS: A systematic search was conducted in OVID Embase, OVID MEDLINE, Cochrane Library, and Web of Science databases on May 2, 2024. Both observational and interventional studies were included if they involved oral metformin use before AMD diagnosis. Data were extracted and analyzed using a random-effects model meta-analysis, with subgroup analyses based on study design, AMD subtype, sex, and metformin dosage.<br><br>RESULTS: Eighteen observational studies were identified, which together included a total of 2&#xa0;683&#xa0;234 individuals. Nine studies had a case-control design, 7 were retrospective cohort studies, and 2 were cross-sectional studies. The meta-analysis revealed a significant reduction in the odds of AMD among metformin users (pooled odds ratio [OR]&#xa0;=&#xa0;0.86, 95% confidence interval&#xa0;=&#xa0;0.79-0.93, P&#xa0;=&#xa0;0.0002, I[2]&#xa0;=&#xa0;90%). The association was significant in both patients with diabetes (pooled OR&#xa0;=&#xa0;0.89) and without diabetes (pooled OR&#xa0;=&#xa0;0.70), although only 2 studies reported nondiabetic ORs. Dose-response analysis revealed significant protective effects at low doses. Sensitivity analysis indicated that the removal of an outlier study did not alter the overall effect. Bias analysis using the Risk of Bias in Nonrandomized Studies of Interventions tool revealed significant risks of bias, particularly due to confounding.<br><br>CONCLUSION: Although the current evidence suggests a potential protective role of metformin in AMD, all studies showing an effect of metformin have been observational and thus subject to bias. Randomized clinical trials are needed to determine the effectiveness of metformin for preventing the onset of AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40230589,
year = {2025},
author = {Nawrocka, ZA and Dulczewska-Cichecka, K and Zając, M and Galus, TA and Trębinska, M and Nawrocki, J},
title = {Switch to Aflibercept After Chronic Treatment With Bevacizumab for Choroidal Neovascularization With Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251330334},
pmid = {40230589},
issn = {2474-1272},
abstract = {Purpose: To present the 5-year anatomic and functional outcomes in patients with choroidal neovascularization (CNV) and age-related macular degeneration (AMD) and determine whether late-onset intensification of treatment results in improved outcomes. Methods: This retrospective interventional study analyzed spectral-domain optical coherence tomography data and visual acuity (VA) in eyes where treatment intensification was implemented after a mean of 39 months. Data collected included age, sex, injection frequency, central retinal thickness, type of CNV, and VA. Patients were evaluated every 4 to 10 weeks, depending on the disease activity. Results: Fifty eyes of 50 patients with CNV were evaluated. The mean initial VA was 0.37 Snellen (0.58 logMAR), which improved to 0.44 Snellen (0.47 logMAR) after the first bevacizumab injection. Six months after bevacizumab was switched to aflibercept, the improvement in VA was significant in all groups (P < .05). The VA improved throughout the 6-year observation period, with the greatest improvement in VA after the switch seen in patients who received the most injections (P < .05), had the best initial VA (P < .05), and who experienced a significantly greater improvement in VA after the first bevacizumab injection (P = .01). Conclusions: Increasing the treatment frequency, even after several years of treatment, improved visual outcomes in patients with CNV and AMD who switched from bevacizumab to aflibercept.},
}
@article {pmid40229856,
year = {2025},
author = {Lee, CN and Desai, R and Ramazzotto, L and Wafa, H and Wang, Y and Bunce, C and Doungsong, K and Ezeofor, V and Edwards, RT and Lois, N and Steel, DH and Peto, T and Hillenkamp, J and van Meurs, JC and Reeves, BC and Jackson, TL},
title = {Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): update to study protocol and addition of a statistical analysis plan and health economic analysis plan for a randomised controlled surgical trial.},
journal = {Trials},
volume = {26},
number = {1},
pages = {131},
pmid = {40229856},
issn = {1745-6215},
support = {2036 / 2037//Fight for Sight UK/ ; },
mesh = {Humans ; *Retinal Hemorrhage/etiology/therapy/economics ; *Tissue Plasminogen Activator/administration &amp; dosage/adverse effects/economics ; *Wet Macular Degeneration/complications ; *Vitrectomy/economics/methods/adverse effects ; Randomized Controlled Trials as Topic ; Intravitreal Injections ; Multicenter Studies as Topic ; Treatment Outcome ; Cost-Benefit Analysis ; *Fibrinolytic Agents/administration &amp; dosage/adverse effects ; Visual Acuity ; },
abstract = {BACKGROUND: The vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER) trial is a pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical clinical trial of an investigational medicinal product.<br><br>METHODS: The original protocol for this trial was published on 31 January 2022 (https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05966-3). This update reports on key changes in the study protocol in version 2.0 which was approved for trial sites from 18 January 2022, and the current version 3.0 which was approved for trial sites from 25 April 2023, and includes current versions of the statistical analysis plan and health economics analysis plan. In summary, there have been changes to three eligibility criteria: removing the word "Actilyse" from exclusion criterion 2, updating exclusion criterion 5 to state abstinence from heterosexual intercourse or the use of highly effective methods of birth control is mandatory for up to 12&#xa0;weeks after last aflibercept exposure on trial, and clarifying exclusion criterion 6 relating to international normalised ratio (INR) is only applicable to participants receiving warfarin. Changes to secondary outcomes include Radner Reading speed being limited to the study eye only, and moving EQ-5D-5L from a secondary reported efficacy outcome to a component of health economic analysis reporting only. Actilyse Cathflo was added as an additional permitted investigational medicinal product as this is already used in practice in the UK and is molecularly identical to Actilyse 10&#xa0;mg. Instructions were added to account for participants who had already been exposed to aflibercept or a similar anti-vascular endothelial growth factor (anti-VEGF) within 21&#xa0;days (the minimum window between anti-VEGF treatments permitted on trial) prior to study enrolment, storage of tissue plasminogen activator in theatre and operating room environments, and the recording of additional, as-needed aflibercept treatments in-between study visits at the discretion of the study investigator. Finally, sections and subsections have been added to detail the imaging analysis plan, patient public involvement plan, INR testing, and recruitment and informed consent components of the trial. The primary analysis of the trial as stated in the statistical analysis plan is the difference between groups in the proportion of participants gaining&#x2009;&#x2265;&#x2009;10 ETDRS letters in their study eye at the month 12 visit, whilst the primary health economic analysis of the trial is the difference in quality-adjusted life years between groups at 12&#xa0;months.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04663750 ; EudraCT: 2020-004917-10.},
}
@article {pmid40229766,
year = {2025},
author = {Kobayashi, Y and Maruyama-Inoue, M and Inoue, T and Yanagi, Y and Kadonosono, K},
title = {Three-year visual outcomes after brolucizumab in patients with neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {207},
pmid = {40229766},
issn = {1471-2415},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Intravitreal Injections ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Tomography, Optical Coherence ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; Aged, 80 and over ; Treatment Outcome ; Fluorescein Angiography ; Retrospective Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Time Factors ; },
abstract = {BACKGROUND: The purpose of this study is to investigate the 3-year outcomes of intravitreal brolucizumab and determine the factors that affect the visual acuity (VA) in patients with neovascular age-related macular degeneration.<br><br>METHODS: All received three consecutive, monthly, induction brolucizumab injections (6.0&#xa0;mg/0.05&#xa0;ml) and fixed-dose every 2-or-3-month treatment for 12 months, after which a pro re nata (PRN) or treat-and-extend (TAE) regimen began. Best-corrected VAs (BCVAs) on a Landolt C eye chart were compared before and 4, 12, and 36 months after initial treatment. Factors affecting VA improvements and morphologic characteristics associated with VA at 36 months were determined.<br><br>RESULTS: Fifty-nine eyes were assessed at 36 months. The mean logMAR BCVAs at baseline and 4, 12, and 36 months after the initial injection were 0.37&#x2009;&#xb1;&#x2009;0.39, 0.34&#x2009;&#xb1;&#x2009;0.48, 0.30&#x2009;&#xb1;&#x2009;0.47, and 0.36&#x2009;&#xb1;&#x2009;0.51 in the PRN group and 0.31&#x2009;&#xb1;&#x2009;0.28, 0.22&#x2009;&#xb1;&#x2009;0.27, 0.18&#x2009;&#xb1;&#x2009;0.28, and 0.20&#x2009;&#xb1;&#x2009;0.31 in the TAE group, respectively. In the PRN group, post-injection BCVA did not improve significantly compared with baseline throughout 36 months (p&#x2009;=&#x2009;0.999, p&#x2009;=&#x2009;0.814, and p&#x2009;=&#x2009;0.999 at 4, 12, and 36 months, respectively). In the TAE group, the post-injection BCVA at 12 and 36 months improved significantly compared with baseline (p&#x2009;=&#x2009;0.006 and p&#x2009;=&#x2009;0.032, respectively). The baseline BCVA, central foveal thickness (CFT) and TAE regimen were associated with improved VA (p&#x2009;<&#x2009;0.05 for all). Eyes with subretinal fluid (SRF) at 36 months had significantly better VA (p&#x2009;=&#x2009;0.019).<br><br>CONCLUSION: The TAE regimen achieved better visual outcomes at 3 years. Residual SRF should be tolerated during the maintenance phase if the change of CFT was little compared to the previous image.},
}
@article {pmid40229571,
year = {2025},
author = {Kataoka, K and Gale, R and Li, X and Şermet, F and Qian, CX and Cheung, CMG and Tsilimbaris, MK and Kozak, I},
title = {Simultaneous GA and CNV/MNV: incidence, characteristics, and treatments.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {5},
pages = {1197-1212},
pmid = {40229571},
issn = {1435-702X},
mesh = {Humans ; *Choroidal Neovascularization/epidemiology/diagnosis/therapy/complications ; Incidence ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Geographic Atrophy/epidemiology/diagnosis/complications/therapy ; Angiogenesis Inhibitors/therapeutic use ; Risk Factors ; Fundus Oculi ; Global Health ; *Disease Management ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: Understanding the clinical characteristics and underlying mechanisms of simultaneous geographic atrophy (GA) and choroidal neovascularization (CNV)/macular neovascularization (MNV) is necessary for the long-term management of late age-related macular degeneration (AMD) in clinical practice.<br><br>METHODS: The authors reviewed the literature on the incidence, risk factors, and clinical characteristics of simultaneous GA and CNV/MNV and developed consensus recommendations for the diagnosis, assessment, and management of simultaneous GA and CNV/MNV in clinical practice.<br><br>RESULTS: The incidence rate of CNV/MNV in eyes with GA is reported as 7.4% per patient-year or 13.8% in 4.1 years, while that of macular atrophy (MA) subsequent to CNV/MNV is reported as 24.4% to 37% in 24 months. Recent studies using optical coherence tomography angiography (OCT-A) revealed the presence of subclinical CNV/MNV in 11% to 16% of eyes with GA. Fundus autofluorescence is used to detect MA; optical coherence tomography (OCT) and OCT-A are useful for detecting MA, especially around the fovea, with OCT-A offering high sensitivity and specificity in the detection of both MA and CNV/MNV. GA and CNV/MNV share the genetic risk factors of HTRA1, complement factor H, complement factors 3 and 2, and ARMS2, and clinical risk factors of large drusen, cuticular drusen, intraretinal hyperreflective foci, and subretinal drusenoid deposits, suggesting that simultaneous GA and CNV/MNV represents a continuum of AMD. Anti-vascular endothelial growth factor therapy for CNV/MNV is reported to have no impact on the speed or magnitude of MA development or enlargement. An association has been observed between CNV subtype and MA progression, with the latter being slower in the presence of type 1 CNV/MNV.<br><br>CONCLUSIONS: These findings suggest there is a high probability of coexistence of GA and CNV/MNV and that they should not be considered separately. Future clinical studies should assess the two conditions simultaneously using OCT and OCT-A.<br><br>KEY MESSAGES: What is known Owing to differences in their clinical characteristics, geographic atrophy (GA) and choroidal neovascularization (CNV)/macular neovascularization (MNV) have historically been regarded as two separate entities; however, several cases of coexistent GA and CNV/MNV have been reported recently in the published literature. What is new The findings of this review confirm that GA and CNV/MNV share common genetic risk factors and clinical characteristics, and suggest that these two entities are part of a continuum of late-stage age-related macular degeneration (AMD). The potential for GA and CNV/MNV to coexist should be considered in any discussion of the long-term management of late AMD; moreover, clinicians should assess for CNV/MNV in patients with GA, and for GA in those with CNV/MNV, using multimodal imaging.},
}
@article {pmid40228605,
year = {2025},
author = {Ozaki, A and Sakai, D and Mandai, M},
title = {hPSC-based treatment of retinal diseases - Current progress and challenges.},
journal = {Advanced drug delivery reviews},
volume = {221},
number = {},
pages = {115587},
doi = {10.1016/j.addr.2025.115587},
pmid = {40228605},
issn = {1872-8294},
mesh = {Humans ; *Retinal Diseases/therapy ; Animals ; Retinal Pigment Epithelium/transplantation/cytology ; *Induced Pluripotent Stem Cells/transplantation ; Stem Cell Transplantation/methods ; Cell- and Tissue-Based Therapy/methods ; },
abstract = {Degenerative retinal diseases, such as age-related macular degeneration (AMD) and inherited retinal diseases (IRDs), cause visual impairment due to irreversible damage to the retinal pigment epithelium (RPE) and photoreceptor cells (PRCs). Currently, no definitive treatment exists. However, cell-based therapies using induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) offer potential solutions for restoring damaged retinal cells. This review summarizes recent advances in RPE and PRC transplantation, highlighting the benefits of each approach. For RPE transplantation, we focus on the outcomes of clinical studies involving three formulations: RPE sheets, RPE suspensions, and RPE strips. In the context of PRC transplantation, we trace the progress from fetal retinal transplantation to the latest studies. Additionally, we discuss our recent clinical work with retinal sheet transplantation and genome-edited retinal organoid sheets, which aim to improve functional integration by reducing bipolar cells in grafts. Finally, with the overall safety of the regenerative cell-based therapies demonstrated in past clinical applications, we explore future prospects for these therapies.},
}
@article {pmid40228558,
year = {2025},
author = {Kim, DW and Kim, MS},
title = {Ten-Year Trends of Fluorescein Angiography in Korea Using Data From the Health Insurance Review and Assessment Service.},
journal = {Journal of Korean medical science},
volume = {40},
number = {14},
pages = {e39},
pmid = {40228558},
issn = {1598-6357},
support = {RS-2023-00210974/NRF/National Research Foundation of Korea/Korea ; },
mesh = {Humans ; Republic of Korea ; *Fluorescein Angiography/trends/economics/statistics &amp; numerical data ; Retrospective Studies ; Middle Aged ; Female ; Male ; Aged ; Adult ; Macular Degeneration/diagnostic imaging/diagnosis ; Health Care Costs ; Health Expenditures ; Diabetic Retinopathy/diagnostic imaging/diagnosis ; Aged, 80 and over ; Insurance, Health ; Young Adult ; },
abstract = {BACKGROUND: Fluorescein angiography (FA) is a diagnostic procedure that is crucial for conditions such as age-related macular degeneration and diabetic retinopathy, and due to its importance, the use of conventional and wide-angle FA (wide FA) is on the rise. This study aimed to analyze the annual trends of conventional and wide FA and the trends of healthcare institutions performing these examinations in Korea.<br><br>METHODS: This retrospective study examined data from the Health Insurance Review and Assessment Service's Health and Medical Big Data Open Portal. We investigated the number of patients who underwent conventional and wide FA procedures performed in Korea from 2014 to 2023, categorized by age group and type of healthcare facility. Additionally, trends in healthcare expenditures were analyzed.<br><br>RESULTS: The number of patients undergoing conventional FA consistently declined, while those receiving wide FA increased steadily, keeping the overall patient count relatively stable. Healthcare costs related to conventional FA gradually decreased, whereas expenses for wide FA rose steadily, contributing to an increase in total medical expenses. Analysis of ten-year age intervals revealed that patients in their 60s were the most frequent recipients of wide FA in every year, except for 2014. The prevalence of wide FA at primary healthcare facilities has been steadily increasing.<br><br>CONCLUSION: The use of wide FA has been steadily increasing, gradually replacing conventional FA, particularly in primary healthcare settings. Overall, medical expenses continue to rise. The findings of this study provide valuable evidence for the efficient allocation of medical resources in the future.},
}
@article {pmid40226888,
year = {2025},
author = {Alvarado-Villacorta, R and Yim, TW and Hernandez-Quintela, E and De La Torre-Gonzalez, E and Loza Munarriz, CA and Martinez-Zapata, MJ},
title = {Surgical interventions for presbyopia.},
journal = {The Cochrane database of systematic reviews},
volume = {4},
number = {4},
pages = {CD015711},
pmid = {40226888},
issn = {1469-493X},
mesh = {Humans ; Bias ; Contrast Sensitivity ; *Presbyopia/surgery ; Quality of Life ; Randomized Controlled Trials as Topic ; Visual Acuity ; },
abstract = {RATIONALE: Presbyopia is a progressive condition that everyone who lives long enough will experience, irrespective of gender, ethnicity, or economic status. A wide range of surgical options has emerged for overcoming near and intermediate visual impairment; however, questions about the effectiveness and safety of these interventions remain unanswered. Given the global burden of presbyopia and the need to improve decision-making practices in tailoring management and allocating scarce resources, it is essential to review the available evidence on this issue systematically.<br><br>OBJECTIVES: The primary objective was to compare the effectiveness and safety of surgical interventions for people with presbyopia; the secondary objective was to produce a brief economic commentary summarizing relevant economic evaluations that have compared different surgical interventions.<br><br>SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, two other databases, and trial registries on 29 February 2024.<br><br>ELIGIBILITY CRITERIA: We included randomized controlled trials in participants with presbyopia, including those who had pseudophakic presbyopia with or without previous corneal refractive surgery, in which one surgical intervention was compared with another or a modified version of the same intervention. We excluded trials that had enrolled participants mainly for cataract surgery or who had other ocular comorbidities such as glaucoma, diabetes mellitus, age-related macular degeneration, or myopic retinopathy.<br><br>OUTCOMES: Outcomes of interest were spectacle independence for near and intermediate vision, change in quality of life (QoL), improvement in or maintenance of binocular uncorrected distance visual acuity (VA), participant satisfaction, change in binocular contrast sensitivity (CS), and frequency of adverse events (AE).<br><br>RISK OF BIAS: We used the Cochrane RoB 2 tool to assess bias for each outcome in each included trial.<br><br>SYNTHESIS METHODS: We planned to synthesize results for each outcome using meta-analysis (random-effect models) where possible, or else use synthesis without meta-analysis methods. However, due to insufficient data for each pairwise comparison (i.e. only one study reported data per analysis), we employed narrative synthesis. We used GRADE to assess the certainty of evidence for each outcome.<br><br>INCLUDED STUDIES: We included four studies that enrolled 300 participants (600 eyes); most participants were women; mean ages ranged between 46 and 58 years. Two trials were conducted in Croatia, one in Egypt, and one in Turkey. Three studies compared a surgical intervention for presbyopia with another, and one study compared a surgical intervention with a modified version of the same intervention. All enrolled participants had presbyopia without cataracts, other comorbidities, or previous ocular surgery. No trials were registered before initiation. One trial reported no funding and no financial conflicts of interest; the others provided no information.<br><br>SYNTHESIS OF RESULTS: Only one study provided data per pairwise comparison of interventions. No study reported outcomes at 12 months or provided economic data. Diffractive bifocal intraocular lens (IOL) versus refractive bifocal IOL after refractive lens exchange (RLE) At six months, the diffractive bifocal IOL group showed no evidence of a difference in spectacle independence for near vision (risk ratio [RR] 1.06, 95% confidence interval [CI] 0.82 to 1.37; 100 participants; low-certainty evidence), intermediate vision (RR 0.93, 95% CI 0.81 to 1.07; 100 participants; low-certainty evidence), or participant satisfaction (RR 1.09, 95% CI 0.99 to 1.19; 100 participants; very low-certainty evidence) compared with refractive bifocal IOL implantation after RLE. Ocular AEs may be less frequent in the diffractive bifocal IOL group (RR [non-event] 1.38, 95% CI 1.05 to 1.81; 100 participants; very low-certainty evidence). Changes in QoL, binocular CS, or binocular uncorrected distance VA were not reported. Diffractive bifocal IOL after RLE versus laser-assisted in situ keratomileusis (LASIK) monovision At six months, diffractive bifocal IOL implantation showed no evidence of a difference compared with LASIK monovision in spectacle independence for near vision (RR 1.07, 95% CI 0.92 to 1.25; 100 participants; low-certainty evidence), the proportion of participants achieving 0.0 LogMAR or better distance vision (RR 0.87, 95% CI 0.69 to 1.11; 100 participants; low-certainty evidence), or improvement in participant satisfaction (RR 0.98, 95% CI 0.89 to 1.07; 100 participants; low-certainty evidence). However, LASIK monovision may improve spectacle independence for intermediate vision at six months (RR 0.82, 95% CI 0.72 to 0.94; 100 participants; low-certainty evidence) and may reduce ocular AE (RR [non-event] 0.58, 95% CI 0.46 to 0.74; 100 participants; very low-certainty evidence). Changes in QoL or binocular CS were not reported. Diffractive trifocal IOL versus extended depth of focus IOL after RLE No data on spectacle independence, participant satisfaction, binocular CS, or ocular AE were reported. At three months after surgery, neither of the two interventions may offer a clinically significant advantage over the other, either for QoL scores (mean difference [MD] -0.08, 95% CI-0.15 to -0.01; 74 participants; very low-certainty evidence) or binocular uncorrected near VA (MD 0.01, 95% CI -0.02 to 0.04; 74 participants), intermediate VA (MD 0.01, 95% CI -0.01 to 0.03; 74 participants) or distance VA (MD 0.01, 95% CI -0.01 to 0.03; 74 participants; low-certainty evidence). Modified wavefront-guided (WG) LASIK versus conventional WG LASIK We found no data for spectacle independence, QoL, participant satisfaction, or ocular AE. Data from one study suggested no evidence of a difference between the interventions in improvement in uncorrected distance VA or change in binocular CS at three months. However, we had concerns about potential bias, and the data were insufficient for quantitative analysis.<br><br>AUTHORS' CONCLUSIONS: The available data were limited to short-term (three months) and mid-term (six months) outcomes and provided low- or very low-certainty evidence. Little information was reported regarding QoL, binocular CS, or ocular AEs; no study addressed economic aspects of interventions.<br><br>FUNDING: This Cochrane review had no internal source of support. External sources: National Eye Institute, National Institutes of Health, USA; Public Health Agency, UK; Queen's University Belfast, UK.<br><br>REGISTRATION: Protocol (2023): doi.org/10.1002/14651858.CD015711.},
}
@article {pmid40226626,
year = {2025},
author = {Omori, T and Machida, T and Ishida, Y and Sekiryu, T and Sekine, H},
title = {Roles of MASP-1 and MASP-3 in the development of retinal degeneration in a murine model of dry age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1566018},
pmid = {40226626},
issn = {1664-3224},
mesh = {Animals ; Disease Models, Animal ; Mice ; *Mannose-Binding Protein-Associated Serine Proteases/genetics/metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; Iodates ; *Geographic Atrophy/pathology/metabolism ; *Macular Degeneration/pathology/metabolism ; *Retinal Degeneration/pathology/metabolism ; Retinal Pigment Epithelium/pathology/metabolism ; },
abstract = {Complement is activated through the three different pathways, which are the classical (CP), lectin (LP), and alternative pathways (AP). Complement activation functions to eliminate invading pathogens, whereas dysregulation of complement activation can induce inflammatory disorders such as age-related macular degeneration (AMD). In retinal degeneration induced by sodium iodate (NaIO3), a murine model of dry AMD (also called atrophic AMD), it has been suggested that the AP and CP are involved in the disease development. On the other hand, the role of the LP in the development of AMD remains unclear. In the current study, we generated murine dry AMD model with NaIO3 using mice deficient for mannose-binding lectin-associated serine protease (MASP)-1 and/or MASP-3, which are required for the LP and AP activation, respectively. Wild-type (WT) C57BL/6J mice showed retinal degeneration, including depigmentation and disruption of the retinal pigment epithelium (RPE), atrophy of the photoreceptor layer (PL), and thinning of the outer nuclear layer (ONL) after NaIO3 injection. In contrast, those pathological changes after NaIO3 injection were significantly attenuated in MASP-1-deficient (MASP-1[-/-]), MASP-3-deficient (MASP-3[-/-]), and MASP-1/3-double deficient (MASP-1/3[-/-]) mice. These results indicate that both MASP-1 and MASP-3 play a role in photoreceptor degeneration in the NaIO3-induced murine dry AMD model. In addition, photoreceptor cell death and retinal C3 activation were observed in NaIO3-injected WT mice, whereas those pathological changes were significantly attenuated in NaIO3-injected MASP-3[-/-] and MASP-1/3[-/-] mice. On the other hand, those pathological changes in NaIO3-injected MASP-1[-/-] mice were comparable to those in NaIO3-injected WT mice. Taken together, our results indicate that MASP-3 plays a pivotal role in C3 activation in the retina most likely via activation of the AP leading to the development of retinal degeneration in the NaIO3-induced murine dry AMD model. Our results also indicate that MASP-1 plays a role in the development of NaIO3-induced retinal degeneration in this murine model, although it remains unclear whether its role in the retinal degeneration is through the LP activation.},
}
@article {pmid40225792,
year = {2025},
author = {Liu, GM and Liu, Y},
title = {Exosomes derived from human umbilical cord blood mesenchymal stem cells protect against blue light-induced damage to retinal pigment epithelial cells by inhibiting FGF2 expression.},
journal = {Cytotechnology},
volume = {77},
number = {3},
pages = {88},
pmid = {40225792},
issn = {0920-9069},
abstract = {Age-related macular degeneration (AMD) is a debilitating retinal disorder that may lead to progressive vision loss. One contributing factor to AMD pathogenesis is excessive blue light (BL) exposure. In this study, we investigated the therapeutic potential of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSC-EXs) in addressing BL-induced damage to ARPE-19 human retinal pigment epithelial (RPE) cells and explored the underlying mechanisms. Our findings revealed that BL exposure induced morphological alterations in ARPE-19 cells, accompanied by a time-dependent decline in cell viability, increased apoptosis, heightened oxidative stress, and inflammatory responses; however, hUCMSC-EXs dose-dependently mitigated BL-induced ARPE-19 cell damage. Interestingly, hUCMSC-EXs were found to suppress the upregulation of fibroblast growth factor 2 (FGF2) in BL-exposed ARPE-19 cells. Furthermore, FGF2 overexpression partially counteracted the inhibitory effects of hUCMSC-EXs on FGF2 expression and compromised the protective benefits of hUCMSC-EXs against BL-induced ARPE-19 cell damage. In conclusion, our results suggest that hUCMSC-EXs shield ARPE-19 cells from BL-induced harm by inhibiting FGF2 expression.},
}
@article {pmid40225410,
year = {2025},
author = {He, F and Chen, Q and Gu, P and Liu, X and Chen, Y and Liu, T and Li, C},
title = {Exploring the Causal Relationships between Lipid Biomarkers and Anti-VEGF Treatment Response in Patients with Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100711},
pmid = {40225410},
issn = {2666-9145},
abstract = {PURPOSE: To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: A bidirectional and multivariable Mendelian randomization study.<br><br>PARTICIPANTS: The summary statistics for anti-VEGF nAMD treatment response included a total of 128 responders, 51 nonresponders, and 6&#xa0;908&#xa0;005 genetic variants available for analysis. The sample size of lipid biomarkers is 441&#xa0;016 and 12&#xa0;321&#xa0;875 genetic variants available for analysis.<br><br>METHODS: Two-sample Mendelian randomization (MR) method was conducted to exhaustively appraise the causalities among 13 lipid biomarkers and the risk of different anti-VEGF treatment responses (including visual acuity [VA] and central retinal thickness [CRT]) for nAMD subtypes.<br><br>MAIN OUTCOME MEASURES: Thirteen lipid biomarkers, VA, and CRT.<br><br>RESULTS: A positive causal relationship was identified between triglycerides (TGs), apolipoproteins (Apos) E2, ApoE3, total cholesterol (TC), and VA response to anti-VEGF therapy in patients with nAMD, as confirmed by MR-Egger, weighted median, and weighted mode models. The MR-Egger model yielded statistically significant results for TC, ApoA-I, ApoB, and ApoA-V in relation to the CRT response to anti-VEGF treatment in patients with nAMD. In the reverse MR, the MR-Egger model identified significant causal relationships between ApoA-I, low-density lipoprotein cholesterol (LDL-c), ApoE3, and ApoF and the VA response. However, this was not the case in the weighted median and weighted mode models. In the MR-Egger model, ApoB, LDL-c, ApoE3, and ApoM were identified as significantly influencing the CRT response. In the multisample MR analysis, TC, high-density lipoprotein cholesterol, LDL-c, and TG were found to be causally related to VA response, and TC was also identified as being causally related to the CRT response to anti-VEGF therapy in patients with nAMD.<br><br>CONCLUSIONS: This MR study suggests unidirectional causality between TG and ApoE3 and the response to anti-VEGF treatment in patients with nAMD.<br><br>FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid40222695,
year = {2025},
author = {Yuan, J and Huang, R and Nao, J and Dong, X},
title = {The role of semaphorin 3A in the pathogenesis and progression of Alzheimer's disease and other aging-related diseases: A comprehensive review.},
journal = {Pharmacological research},
volume = {215},
number = {},
pages = {107732},
doi = {10.1016/j.phrs.2025.107732},
pmid = {40222695},
issn = {1096-1186},
mesh = {Humans ; *Semaphorin-3A/metabolism ; *Alzheimer Disease/metabolism/pathology/drug therapy ; *Aging/metabolism ; Animals ; Disease Progression ; Oxidative Stress ; },
abstract = {Aging serves as a pivotal factor in the etiology of numerous diseases, such as Alzheimer's disease (AD), Parkinson's disease, diabetes, osteoarthritis, atherosclerosis and aging-related macular degeneration. Notably, these diseases often interact with AD through various pathways, facilitating the onset or progression of one another. Semaphorin 3 A (Sema3A), a protein that is essential for axonal guidance during neural development, has recently been identified as a novel regulator in the pathogenesis and progression of multiple aging-related diseases. This article provides a comprehensive review of the expression patterns and mechanisms of action of Sema3A in these diseases. Specifically, Sema3A influences the occurrence and development of aging-related diseases by participating in oxidative stress, inflammatory responses, apoptosis, and synaptic plasticity. Therefore, therapeutic strategies targeting Sema3A present promising avenues for delaying the progression of aging-related diseases and offer novel insights and strategies for their treatment.},
}
@article {pmid40222639,
year = {2025},
author = {Hasan, N and Zarnegar, A and Jacob, N and Sahoo, N and Saju, S and Zhou, A and Wykoff, CC and Winter, H and Gill, M and Silva, R and Pereira, P and Hertkorn, F and Desideri, LF and Munk, MR and Villafuerte-Trisolini, C and Yiu, G and Wu, L and Chhablani, J and , },
title = {Clinical Characteristics and Progression of Pachychoroid Macular Atrophy in Central Serous Chorioretinopathy.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {10},
pages = {984-993},
doi = {10.1016/j.oret.2025.04.005},
pmid = {40222639},
issn = {2468-6530},
mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; Disease Progression ; *Fluorescein Angiography/methods ; *Central Serous Chorioretinopathy/diagnosis/complications ; Middle Aged ; Follow-Up Studies ; *Macula Lutea/pathology ; Fundus Oculi ; *Visual Acuity ; *Retinal Pigment Epithelium/pathology ; Aged ; Atrophy/etiology ; *Choroid/pathology ; },
abstract = {PURPOSE: Macular atrophy (MA) is a late-stage complication often associated with age-related macular degeneration (AMD). However, it can also occur in pachychoroid diseases, including central serous chorioretinopathy (CSCR), called pachychoroid MA (pMA). This study aimed to investigate the characteristics and progression of pMA in CSCR.<br><br>DESIGN: Multicenter retrospective study as part of the Macula Society International CSCR Research Network (MICRoN).<br><br>PARTICIPANTS: Thirty-eight eyes of 32 patients.<br><br>METHODS: Demographic and imaging data were collected. OCT and fundus autofluorescence images were analyzed to identify pMA features, including complete retinal pigment epithelium and outer retinal atrophy, pachychoroid phenotype, and baseline CSCR characteristics. The study comprised 2 parts: (1) progression analysis, comparing time to pMA among OCT features in cases without baseline pMA; and (2) follow-up analysis, including patients with at least a 12-month interval between 2 visits showing pMA progression. Pachychoroid macular atrophy area, number, and location were manually measured using the HEYEX-2 platform and ImageJ.<br><br>MAIN OUTCOME MEASURES: Progression analysis: OCT features that contributed to faster development of pMA. Follow-up analysis: progression rate of pMA after square root transformation (SQRT) and features that contribute to faster progression in lesion size.<br><br>RESULTS: Among 1675 eyes with CSCR, the prevalence of pMA was 2.27% and the incidence of pMA was 0.89%. Eyes with intraretinal fluid (IRF) experienced faster time to development of pMA (31.34 &#xb1; 16.66 months) compared with those without IRF (64.13 &#xb1; 37.14 months, P = 0.039). The mean pMA area increased from 1.65 &#xb1; 2.09 mm[2] to 3.08 &#xb1; 3.14 mm[2], with a mean progression rate of 0.29 &#xb1; 0.28 mm[2]/year. Central pMA exhibited a faster progression rate than noncentral pMA (0.13 &#xb1; 0.078 mm[2]/year vs. 0.052 &#xb1; 0.055 mm[2]/year, P = 0.011). Larger baseline pMA area was significantly associated with quicker progression (r = 0.65, P &#x2264; 0.001). However, after SQRT of pMA area, no significant association with baseline area was found. There was significant reduction of central macular thickness (195.72 &#xb1; 96.58 to 153.64 &#xb1; 100.25 microns, P = 0.034) and subfoveal choroidal thickness (372.92 &#xb1; 83.84 to 342.8 &#xb1; 78.33 microns, P value = 0.029) at follow-up.<br><br>CONCLUSIONS: Pachychoroid MA in CSCR exhibits distinct characteristics compared with AMD-related geographic atrophy from established literature. It progresses at a slower rate, and larger lesions tend to advance more rapidly. Additionally, central pMA progresses faster than noncentral pMA. The presence of IRF during the disease course accelerates the progression of CSCR to pMA.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40221802,
year = {2025},
author = {Álvarez-Barrios, A and Álvarez, L and Sáenz de Santa María, P and García, M and Álvarez-Buylla, JR and Pereiro, R and González-Iglesias, H},
title = {Dysregulated lipid metabolism in a retinal pigment epithelial cell model and serum of patients with age-related macular degeneration.},
journal = {BMC biology},
volume = {23},
number = {1},
pages = {96},
pmid = {40221802},
issn = {1741-7007},
support = {PID2022-137319OB-C22//Ministerio de Ciencia e Innovaci&#xf3;n/ ; PID2022-137319OB-C22//Ministerio de Ciencia e Innovaci&#xf3;n/ ; PID2022-137319OB-C22//Ministerio de Ciencia e Innovaci&#xf3;n/ ; PID2022-137319OB-C22//Ministerio de Ciencia e Innovaci&#xf3;n/ ; PID2022-137319OB-C22//Ministerio de Ciencia e Innovaci&#xf3;n/ ; PID2022-137319OB-C22//Ministerio de Ciencia e Innovaci&#xf3;n/ ; FPU20/00608//Ministerio de Educaci&#xf3;n y Formaci&#xf3;n Profesional/ ; FPU20/00608//Ministerio de Educaci&#xf3;n y Formaci&#xf3;n Profesional/ ; C&#xe1;tedra Rafael del Pino//Fundaci&#xf3;n Rafael del Pino/ ; C&#xe1;tedra Rafael del Pino//Fundaci&#xf3;n Rafael del Pino/ ; },
mesh = {Humans ; *Macular Degeneration/blood/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *Lipid Metabolism/genetics ; Aged ; Cells, Cultured ; Male ; Female ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness, characterized by retinal pigment epithelium (RPE) dysfunction, extracellular deposit formation, and disrupted lipid metabolism. Understanding the molecular changes underlying AMD is essential for identifying diagnostic markers and therapeutic targets.<br><br>RESULTS: This multiomic study employed a primary RPE culture model to investigate age-related changes associated with AMD. Over 25 weeks, RPE cells exhibited phenotypic deterioration, including depigmentation, cell shape deformation, and barrier integrity loss, accompanied by extracellular deposit formation. Transcriptomic analysis revealed dysregulation of genes involved in lipid metabolism, including pathways for cholesterol transport, glycerophospholipids, and ceramide biosynthesis. Metabolomic profiling further identified significant changes in glycerophospholipid and sphingolipid metabolism, highlighting a decline in phospholipid species and ceramide accumulation. Serum analysis of AMD patients revealed altered levels of 18 lipids identified in RPE cultures. Four lipids showed significant differences compared to controls: GlcCer(d16:1/18:0) (1.23-fold increase, adj. p value&#x2009;<&#x2009;0.001), PE(19:1(9Z)/22:2(13Z,16Z)) (0.34-fold decrease, adj. p value&#x2009;<&#x2009;0.001), PE(15:0/20:3(5Z,8Z,11Z)) (0.66-fold decrease, adj. p value&#x2009;<&#x2009;0.05), and PC(22:2(13Z,16Z)/13:0) (0.71-fold decrease, adj. p value&#x2009;<&#x2009;0.05). These findings underscore the systemic nature of lipid dysregulation in AMD and the translational relevance of the RPE model.<br><br>CONCLUSIONS: This study highlights the significant role of lipid metabolism dysregulation in AMD pathogenesis. The consistent lipidomic alterations observed in RPE cultures and AMD patient serum reinforce their potential as biomarkers for disease progression and therapeutic targets. These findings provide a robust framework for understanding AMD-associated lipid metabolism changes and their systemic impact.},
}
@article {pmid40221561,
year = {2025},
author = {Huang, AY and Ehrlich, JR and Hamedani, AG},
title = {Visual impairment, age-related eye disease, and sleep dysfunction in older adults.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {2008-2014},
pmid = {40221561},
issn = {1476-5454},
support = {R01 EY034479/EY/NEI NIH HHS/United States ; K23EY033438-03//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R61AG089063//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R61 AG089063/AG/NIA NIH HHS/United States ; U01 AG032947/AG/NIA NIH HHS/United States ; R01EY034479//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; K23 EY033438/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; Aged ; Aged, 80 and over ; *Sleep Wake Disorders/epidemiology/physiopathology ; United States/epidemiology ; Visual Acuity/physiology ; *Vision Disorders/epidemiology/physiopathology ; Contrast Sensitivity/physiology ; Self Report ; *Persons with Visual Disabilities/statistics &amp; numerical data ; Glaucoma/epidemiology ; *Aging/physiology ; Macular Degeneration/epidemiology ; *Eye Diseases/epidemiology ; },
abstract = {BACKGROUND/OBJECTIVES: The visual system affects circadian rhythms, and both visual and sleep difficulties are common in older adults. This study examines the association between visual impairment, age-related eye disease, and sleep disturbances among older adults in the United States.<br><br>SUBJECTS/METHODS: This cross-sectional study used Round 11 of the National Health and Aging Trends Study (NHATS). Vision was assessed using self-report and objective assessments (distance and near acuity, contrast sensitivity). Medicare claims data were used to identify diagnoses of age-related macular degeneration, glaucoma, diabetic retinopathy, and cataract. Primary outcomes included self-reported sleep disturbances, defined by difficulties in sleep initiation, maintenance, and medication use. Logistic regression models were adjusted for demographic and clinical variables.<br><br>RESULTS: Among 3817 participants (56% female), difficulty with sleep initiation, maintenance, and medication use were reported by 41.7%, 44.2%, and 26.5% of the cohort, respectively. In unadjusted models, self-reported visual difficulty was associated with sleep initiation (OR 1.80, 95% CI: 1.43-2.29) and maintenance difficulties (OR 1.53, 95% CI: 1.16-2.02) and sleep medication use (OR 1.68, 95% CI: 1.27-2.24). After adjusting for covariates, self-reported visual difficulty remained significantly associated with sleep medication use (OR 1.40, 95% CI: 1.00-1.95). Near acuity and contrast sensitivity were associated with sleep initiation difficulties but did not remain significant after adjustment. No associations were found between ophthalmic diagnoses and outcomes.<br><br>CONCLUSION: Self-reported visual difficulty is associated with increased sleep medication use in older adults. Because visual impairment and sleep medications are associated with falls and cognitive decline, future studies should consider these comorbidity patterns.},
}
@article {pmid40221144,
year = {2025},
author = {Cui, J and Lu, H and Wang, S and Li, Z and Song, X and Xiu, W and Liu, B and Li, J and Jin, C and Zhao, A and Ding, H and Sun, D and Jablonski, MM and Lu, L and Gu, W and Yang, B},
title = {Genotypes of SNPs of key genes regulate susceptibility and drug sensitivity to neovascular AMD in the human population.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40221144},
issn = {2397-3269},
mesh = {Humans ; *Polymorphism, Single Nucleotide ; Male ; Female ; Aged ; Case-Control Studies ; Prospective Studies ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/genetics/drug therapy/diagnosis ; Genotype ; *Genetic Predisposition to Disease ; High-Temperature Requirement A Serine Peptidase 1/genetics ; Complement Factor H/genetics ; *Proteins/genetics ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Complement C3/genetics ; Complement Factor B/genetics ; Aged, 80 and over ; Serine Endopeptidases/genetics ; },
abstract = {OBJECTIVE: To compare the genetic characteristics of the normal control group to those of neovascular age-related macular degeneration (AMD) patients and to detect single-nucleotide polymorphisms (SNPs) related to the pathogenesis of neovascular AMD and the sensitivity to anti-VEGF drug, combercept.<br><br>METHOD: This is a prospective case-controlled study. A total of 104 neovascular AMD patients were treated with combercept and 106 normal subjects were served as the control group. SNPs associated with neovascular AMD and disease susceptibility and drug sensitivity were analysed.<br><br>RESULTS: Significant differences existed between neovascular AMD patients and normal subjects among genotypes of the SNPs of two genes, ARMS2 (rs10490924 T) and HTRA 1 (rs11200638 A). The T alleles in rs1065489 of CFH and the rs2230205 of C3 significantly promoted neovascular AMD in males while having no significant effect in females. Six SNPs of five genes, including C3 (rs2250656 G), CFB (rs2072633 G), CFH (rs2274700 A, rs3766405 T), KDR (rs6828477 A) and FZD 4 (rs10898563 T), had significant impact in reducing neovascular AMD. Two SNPs of the CFH gene (rs2274700 A and rs3766405 T) and one SNP of the CFB gene, rs2072633 G, were statistically significantly associated with good response to combercept. Conversely, the other two SNPs of the CFH gene, rs1065489 T and rs3753396 G, and the rs7412 T of the APOE gene were associated with a relatively poor patient response to drug action. Two sets of SNPs of CFB have a combined positive effect on disease. The two SNPs of CFH (rs1065489 T and rs3753396 G) and the combination of the two SNPs of CFH and rs7412T of APOE have negative effects on the drug effectiveness.<br><br>CONCLUSIONS: These genotype differences facilitate the selection of individualised treatment options towards obtaining the most efficacious clinical treatment. These findings need to be validated by studies with different ethnic populations and/or larger samples.},
}
@article {pmid40220174,
year = {2025},
author = {Asadi Khameneh, E and Asadigandomani, H and Khalili Pour, E and Sadeghi, R and Mirzaei, A and Bayan, N and Shojaei, S and Mohammadi, N and Fadaei Fard, S and Faghihi, H and Riazi-Esfahani, H},
title = {Treating or tolerating persistent subretinal fluid in neovascular age-related macular degeneration: a systematic review of visual and anatomical outcomes with anti-VEGF therapy.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {154},
pmid = {40220174},
issn = {1573-2630},
mesh = {Humans ; *Subretinal Fluid ; *Visual Acuity ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Recombinant Fusion Proteins/administration &amp; dosage ; },
abstract = {PURPOSE: The management of persistent subretinal fluid (SRF) in neovascular age-related macular degeneration (nAMD) varies, with no comprehensive review of outcomes from different treatment approaches. This systematic review evaluates the efficacy of interventions for managing persistent SRF in nAMD patients.<br><br>METHODS: Using a structured search strategy, a systematic review examined anti-vascular endothelial growth factor (VEGF) treatments for nAMD with persistent SRF. After removing duplicates, 861 articles were screened, 255 underwent full-text review, and 19 met the eligibility criteria.<br><br>RESULTS: The included studies demonstrated variable outcomes regarding the management of persistent SRF in nAMD. Several studies supported tolerating SRF, showing no significant difference in visual acuity between patients with and without persistent SRF. Conversely, some studies advocated for more aggressive treatment, demonstrating a significant reduction in SRF and potential visual benefits. Patients with SRF generally have better visual outcomes compared to those with intraretinal fluid or cysts. High-frequency anti-VEGF regimens, especially with aflibercept, reduce SRF and maintain visual acuity. However, less aggressive protocols achieve stable outcomes with fewer injections.<br><br>CONCLUSION: Persistent SRF in nAMD does not necessarily lead to worse visual outcomes. Standardized protocols and further research are needed to improve management strategies.},
}
@article {pmid40218183,
year = {2025},
author = {Ahn, SJ},
title = {Retinal Thickness Analysis Using Optical Coherence Tomography: Diagnostic and Monitoring Applications in Retinal Diseases.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {7},
pages = {},
pmid = {40218183},
issn = {2075-4418},
abstract = {Retinal thickness analysis using optical coherence tomography (OCT) has become an indispensable tool in retinal disease management, providing high-resolution quantitative data for diagnosis, monitoring, and treatment planning. This analysis has been found to be particularly useful for both diagnostic and monitoring purposes across a wide range of retinal diseases, enabling precise disease characterization and treatment evaluation. This paper explores its applications across major retinal conditions, including age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and inherited retinal diseases. Emerging roles in other diseases such as neurodegenerative diseases and retinal drug toxicity are also highlighted. Despite challenges such as variability in measurements, segmentation errors, and interpretation difficulties, advancements in artificial intelligence and machine learning have significantly improved accuracy and efficiency. The integration of retinal thickness analysis with telemedicine platforms and standardized protocols further underscores its potential in delivering personalized care and enabling the early detection of ocular and systemic diseases. Retinal thickness analysis continues to play a pivotal and growing role in both clinical practice and research, bridging the gap between ophthalmology and broader medical fields.},
}
@article {pmid40217940,
year = {2025},
author = {Morioka, M and Takamura, Y and Yoshida, S and Mori, J and Sawada, T and Matsubara, H and Kusuhara, S and Murakami, T and Kato, A and Tabuchi, H and Nagasato, D and Ueda, T and Shimura, M and Hirano, T and Jujo, T and Mitamura, Y and Nishigaki, M and Harimoto, K and Sasaki, M and Inatani, M},
title = {Comparison of Endophthalmitis Rates Between Prefilled Syringes and Standard Vials in Aflibercept Intravitreal Injections: A Retrospective Study in Japan.},
journal = {Journal of clinical medicine},
volume = {14},
number = {7},
pages = {},
pmid = {40217940},
issn = {2077-0383},
abstract = {Background: Bacterial endophthalmitis is a rare but serious complication of intravitreal injections (IVIs). Prefilled syringes have been introduced to reduce contamination risk during drug preparation. However, whether they lower the incidence of bacterial endophthalmitis compared to vials remains unclear. Methods: This retrospective cohort study analyzed aflibercept IVIs performed at 17 clinical centers in Japan between 2015 and 2022. Patients aged ≥20 years who received aflibercept IVIs (vial or prefilled syringe) for age-related macular degeneration, diabetic macular edema, retinal vein occlusion, or myopic choroidal neovascularization were included. Bacterial endophthalmitis was diagnosed based on clinical signs (e.g., rapid vision loss, pain, hypopyon, vitreous opacity). Incidence rates were compared using Fisher's exact test. Results: Among 152,039 injections (43,684 prefilled syringes; 108,355 vials), 12 cases of bacterial endophthalmitis were identified (0.0046% vs. 0.0092%, p = 0.53). Poor visual outcomes were associated with Enterococcus faecalis, Streptococcus spp., and diabetes. Conclusions: Although incidence was lower in the prefilled syringe group, the difference was not statistically significant. Detecting a significant difference requires a larger sample. Further studies are needed to confirm the potential benefits of prefilled syringes in reducing endophthalmitis risk.},
}
@article {pmid40217821,
year = {2025},
author = {Hatz, K and Ambresin, A and Schmid, M and Prünte, C and Barthelmes, D and Machewitz, T and Allmeier, H and Somfai, GM and , },
title = {Two-Year Switzerland Cohort Results from a Global Observational Study Investigating Proactive Dosing with Intravitreal Aflibercept 2 mg in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {7},
pages = {},
pmid = {40217821},
issn = {2077-0383},
support = {n/a//Bayer AG/ ; },
abstract = {Background/Objectives: XTEND is the largest global, prospective, observational study of treatment-naïve patients with neovascular age-related macular degeneration (nAMD) receiving 2 mg of intravitreal aflibercept (IVT-AFL) in routine clinical practice designed to examine the real-world effectiveness of IVT-AFL proactive treatment regimens. The outcomes from the Switzerland cohort are reported here. Methods: Patients aged ≥50 years were eligible if they planned to receive IVT-AFL 2 mg. After three initial monthly IVT-AFL injections, treatment intervals could be extended (4-week minimum treatment interval). Visual and anatomic outcomes, treatment exposure, and safety were assessed. Statistics were descriptive. Results: Fifty-one patients were treated. At baseline, the mean ± standard deviation (SD) best-corrected visual acuity (BCVA) was 64.9 ± 17.9 letters, and central subfield thickness (CST) was 402 ± 106 µm. At month (M) 12 and M24, the mean (95% confidence interval [CI]) change from baseline in BCVA was +5.7 (1.9, 9.4) and +5.6 (1.3, 9.8) letters, respectively. In patients with a high baseline BCVA (≥70 letters [n = 28; mean ± SD: 77.5 ± 4.8 letters]), BCVA was maintained at ≥70 letters at M12 and M24 (mean change from baseline [range] +1.0 [-15.0, 11.0] and +1.1 [-10.0, 14.0], respectively). At M12 and M24, the mean (95% CI) change in CST was -125 (-161, -90) µm and -127 (-162, -93) µm, respectively. Patients received a mean ± SD of 9.5 ± 3.2 and 13.7 ± 6.0 injections by M12 and M24, respectively. No safety concerns were identified. Conclusions: In Swiss routine clinical practice, functional and anatomic improvements were achieved with IVT-AFL 2 mg proactive treatment in patients with nAMD over 24 months despite a relatively high baseline BCVA.},
}
@article {pmid40217505,
year = {2025},
author = {Hafner, M and Eckardt, F and Siedlecki, J and Schworm, B and Herold, TR and Asani, B and Priglinger, SG and Schiefelbein, JB},
title = {Deep learning assisted analysis of biomarker changes in refractory neovascular AMD after switch to faricimab.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {44},
pmid = {40217505},
issn = {2056-9920},
abstract = {BACKGROUND: Artificial intelligence (AI)-driven biomarker segmentation offers an objective and reproducible approach for quantifying key anatomical features in neovascular age-related macular degeneration (nAMD) using optical coherence tomography (OCT). Currently, Faricimab, a novel bispecific inhibitor of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), offers new potential in the management of nAMD, particularly in treatment-resistant cases. This study utilizes an advanced deep learning-based segmentation algorithm to analyze OCT biomarkers and evaluate the efficacy and durability of Faricimab over nine months in patients with therapy-refractory nAMD.<br><br>METHODS: This retrospective real-world study analyzed patients with treatment-resistant nAMD who switched to Faricimab following inadequate responses to ranibizumab or aflibercept. Automated segmentation of key OCT biomarkers - including fibrovascular pigment epithelium detachment (fvPED), intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), choroidal volume, and central retinal thickness (CRT) - was conducted using a deep learning algorithm based on a convolutional neural network.<br><br>RESULTS: A total of 46 eyes from 41 patients completed the nine-month follow-up. Significant reductions in SRF, fvPED, and choroidal volume were observed from baseline (mo0) to three months (mo3) and sustained at nine months (mo9). CRT decreased significantly from 342.7 (interquartile range (iqr): 117.1) &#xb5;m at mo0 to 296.6 (iqr: 84.3) &#xb5;m at mo3 and 310.2 (iqr: 93.6) &#xb5;m at mo9. The deep learning model provided precise quantification of biomarkers, enabling reliable tracking of disease progression. The median injection interval extended from 35 (iqr: 15) days at mo0 to 56 (iqr: 20) days at mo9, representing a 60% increase. Visual acuity remained stable throughout the study. Correlation analysis revealed that higher baseline CRT and fvPED volumes were associated with greater best-corrected visual acuity (BCVA) improvements and longer treatment intervals.<br><br>CONCLUSIONS: This study highlights the potential of AI-driven biomarker segmentation as a precise and scalable tool for monitoring disease progression in treatment-resistant nAMD. By enabling objective and reproducible analysis of OCT biomarkers, deep learning algorithms provide critical insights into treatment response. Faricimab demonstrated significant and sustained anatomical improvements, allowing for extended treatment intervals while maintaining disease stability. Future research should focus on refining AI models to improve predictive accuracy and assessing long-term outcomes to further optimize disease management.<br><br>TRIAL REGISTRATION: Ethics approval was obtained from the Institutional Review Board of LMU Munich (study ID: 20-0382). This study was conducted in accordance with the Declaration of Helsinki.},
}
@article {pmid40216356,
year = {2025},
author = {Vejux, A and Ghzaiel, I and Mackrill, JJ and Dias, IHK and Rezig, L and Ksila, M and Zarrouk, A and Nury, T and Brahmi, F and El Midaoui, A and Meziane, S and Atanasov, AG and Hammami, S and Latruffe, N and Jouanny, P and Lizard, G},
title = {Oxysterols, age-related-diseases and nutritherapy: Focus on 7-ketocholesterol and 7β-hydroxycholesterol.},
journal = {Prostaglandins &amp; other lipid mediators},
volume = {178},
number = {},
pages = {106993},
doi = {10.1016/j.prostaglandins.2025.106993},
pmid = {40216356},
issn = {1098-8823},
mesh = {Humans ; *Ketocholesterols/metabolism ; *Hydroxycholesterols/metabolism ; Animals ; *Aging/metabolism ; *Oxysterols/metabolism ; Oxidative Stress ; },
abstract = {Age-related diseases are often associated with a disruption of RedOx balance that can lead to lipid peroxidation with the formation of oxysterols, especially those oxidized on carbon-7: 7-ketocholesterol (also known as 7-oxo-cholesterol) and 7β-hydroxycholesterol. Like cholesterol, these oxysterols have 27 carbons, they are composed of a sterane nucleus and have a hydroxyl function in position 3. The oxysterols 7-ketocholesterol and 7β-hydroxycholesterol are mainly formed by cholesterol autoxidation and are biomarkers of oxidative stress. These two oxysterols are frequently found at increased levels in the biological fluids (plasma, cerebrospinal fluid), tissues and/or organs (arterial wall, retina, brain) of patients with age-related diseases, especially cardiovascular diseases, neurodegenerative diseases (mainly Alzheimer's disease), ocular diseases (cataract, age-related macular degeneration), and sarcopenia. Depending on the cell type considered, 7-ketocholesterol and 7β-hydroxycholesterol induce either caspase- dependent or -independent types of cell death associated with mitochondrial and peroxisomal dysfunctions, autophagy and oxidative stress. The caspase dependent type of cell death associated with oxidative stress and autophagy is defined as oxiapoptophagy. These two oxysterols are also inducers of inflammation. These biological features associated with the toxicity of 7-ketocholesterol, and 7β-hydroxycholesterol are often observed in patients with age-related diseases, suggesting an involvement of these oxysterols in the pathophysiology of these disorders. The cytotoxic effects of 7-ketocholesterol and 7β-hydroxycholesterol are counteracted on different cell models by representative nutrients of the Mediterranean diet: ω3 and ω9 fatty acids, polyphenols, and tocopherols. There are also evidences, mainly in cardiovascular diseases, of the benefits of α-tocopherol and phenolic compounds. These in vitro and in vivo observations on 7-ketocholesterol and 7β-hydroxycholesterol, which are frequently increased in age-related diseases, reinforce the interest of nutritherapeutic treatments to prevent and/or cure age-related diseases currently without effective therapies.},
}
@article {pmid40215317,
year = {2025},
author = {Rowe, AA and Velasquez, MJ and Aumeier, JW and Reyes, S and Yee, T and Nettesheim, ER and McDonald, JG and Wert, KJ},
title = {Female sex hormones exacerbate retinal neurodegeneration.},
journal = {Science advances},
volume = {11},
number = {15},
pages = {eadr6211},
pmid = {40215317},
issn = {2375-2548},
support = {T32 GM131945/GM/NIGMS NIH HHS/United States ; F31 EY036730/EY/NEI NIH HHS/United States ; R21 EY034597/EY/NEI NIH HHS/United States ; P01 HL160487/HL/NHLBI NIH HHS/United States ; P30 EY030413/EY/NEI NIH HHS/United States ; P30 DK127984/DK/NIDDK NIH HHS/United States ; UL1 TR003163/TR/NCATS NIH HHS/United States ; },
mesh = {Female ; Animals ; *Gonadal Steroid Hormones/metabolism ; Male ; Mice ; *Retinal Degeneration/metabolism/pathology/genetics/etiology ; Humans ; Disease Models, Animal ; Endoplasmic Reticulum Stress ; Apoptosis ; Sex Factors ; Pyroptosis/genetics ; Retina/pathology/metabolism ; Neurodegenerative Diseases/metabolism ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease and macular degeneration represent major sources of human suffering, yet factors influencing disease severity remain poorly understood. Sex has been implicated as one modifying factor. Here, we show that female sex is a risk factor for worsened outcomes in a model of retinal degeneration and that this susceptibility is caused by the presence of female-specific sex hormones. The adverse effect of female sex hormones was specific to diseased retinal neurons, and depletion of these hormones ameliorated this phenotypic effect, while reintroduction worsened rates of disease in females. Transcriptional analysis of retinas showed significant differences between genes involved in pyroptosis, inflammatory responses, and endoplasmic reticulum stress-induced apoptosis between males and females with retinal degeneration. These findings provide crucial insights into the pathogenesis of neurodegenerative diseases and how sex hormones can affect disease severity. These findings have far-reaching implications for clinical trial design and the use of hormonal therapy in females with certain neurodegenerative disorders.},
}
@article {pmid40212936,
year = {2025},
author = {Dunbar, HMP and Crabb, DP and Behning, C and Binns, AM and Abdirahman, A and Terheyden, JH and Poor, S and Finger, RP and Leal, S and Tufail, A and Holz, FG and Schmid, M and Luhmann, UFO and , },
title = {Heterogeneous Visual Function Deficits in Intermediate Age-Related Macular Degeneration: A MACUSTAR Report.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100708},
pmid = {40212936},
issn = {2666-9145},
abstract = {OBJECTIVE: To examine the extent to which visual function in Beckman age-related macular degeneration (AMD) disease stages differs from age-similar peers with no AMD and, using reference limits derived from those with no AMD, test the hypothesis that people with intermediate AMD (iAMD) have heterogeneous visual function deficits.<br><br>DESIGN: Cross-sectional analyses of a range of baseline visual function measures from the MACUSTAR study-an international, multicenter (n&#xa0;=&#xa0;20), noninterventional clinical trial.<br><br>PARTICIPANTS: Five hundred eighty-five participants with iAMD (67% female, mean [standard deviation] age 72 [7] years) were recruited alongside 56 with no AMD (59% female, 68 [6]), 34 with early AMD (79% female, 72 [6]), and 43 with late AMD (49% female, 75 [6]).<br><br>METHODS: Participants performed best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), Moorfields acuity test (MAT), Pelli-Robson contrast sensitivity (PR-CS), small print standardized International reading speed test (SPS), mesopic and scotopic average threshold (MesAT and ScoAT; macular integrity assessment, iCare), and rod intercept time (RIT; AdaptDx, Lumithera).<br><br>MAIN OUTCOME MEASURES: Relationship between each visual function measure and disease classification was examined by linear regression adjusted for age, sex, and phakic status. No AMD data were used to estimate normal reference limits for each visual function test. Intermediate AMD scores were dichotomized against reference limits, and the proportion worse than each limit was calculated.<br><br>RESULTS: Relative to no AMD, SPS was significantly worse in early AMD (P&#xa0;= 0.001); all measures except SPS were significantly reduced in iAMD (P&#xa0;<&#xa0;0.02), and all measures were markedly reduced in late AMD (P&#xa0;<&#xa0;0.0001). Thirty-one point three percent of iAMD participants breached reference limits for PR-CS, 29.4% for RIT, 24.1% for LLVA, 23.2% for MAT, 20.5% for BCVA, 19.8% for MesAT, 17.9% for ScoAT, and 12.6% for SPS. Of the iAMD participants, 69.6% and 42.7% breached &#x2265;1 and&#xa0;&#x2265;2 reference limits, respectively, whereas 33.6% and 5.7% would be expected by chance.<br><br>CONCLUSIONS: A large proportion of people with structurally defined iAMD exhibit heterogeneous visual function deficits outside normal reference limits. This observation may be relevant for the design and inclusion criteria of future interventional trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40212934,
year = {2025},
author = {Savastano, MC and Fossataro, C and Berni, A and Savastano, A and Cestrone, V and Giannuzzi, F and Boselli, F and Carlà, MM and Cusato, M and Mottola, F and Pirolo, R and D'Agostino, E and Biagini, I and Marcelli, S and Gravina, A and Shen, M and Rizzo, C and Valentini, CG and Bianchi, M and Teofili, L and Cheng, Y and Wang, RK and Rosenfeld, PJ and Rizzo, S},
title = {Intravitreal Injections of Cord Blood Platelet-Rich Plasma in Dry Age-Related Macular Degeneration: Regenerative Therapy.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100732},
pmid = {40212934},
issn = {2666-9145},
abstract = {PURPOSE: Intravitreal injections (IVIs) of umbilical cord blood platelet-rich plasma (CB-PRP) were investigated to assess their safety and efficacy in slowing the progression of atrophy in eyes with late-stage dry age-related macular degeneration (AMD).<br><br>DESIGN: Randomized, controlled, prospective study.<br><br>SUBJECTS: Patients with AMD aged >65 years and diagnosed with bilateral geographic atrophy were enrolled.<br><br>METHODS: One eye of each subject received the treatment of intravitreal CB-PRP 0.05&#xa0;ml, while the fellow eye received a sham injection. Atrophic areas were identified as large choroidal hypertransmission defects (hyperTDs) on en face subretinal pigment epithelium slabs (64-400&#xa0;&#x3bc;m beneath Bruch's membrane) obtained 0.321 from swept-source OCT angiography scans. The main outcome was the mean annualized growth rate of the square root transformed area measurements in both treated and nontreated eyes.<br><br>MAIN OUTCOME MEASURES: The mean&#xa0;&#xb1;&#xa0;standard deviation (SD) square root hyperTD area in the treated eyes was 3.30&#xa0;&#xb1;&#xa0;0.99&#xa0;mm at baseline and 3.49&#xa0;&#xb1;&#xa0;0.98&#xa0;mm after CB-PRP (IVI). In nontreated eyes, the mean square root hyperTD area was 2.96&#xa0;&#xb1;&#xa0;0.94&#xa0;mm at baseline and 3.18&#xa0;&#xb1;&#xa0;0.94&#xa0;mm after sham injections.<br><br>RESULTS: Twenty-six eyes of 13 patients were included. In treated eyes, the mean&#xa0;&#xb1;&#xa0;SD best-corrected visual acuity (BCVA) was 48.92&#xa0;&#xb1;&#xa0;16.33 letters at baseline and 51.46&#xa0;&#xb1;&#xa0;12.27 letters at last follow-up. In untreated eyes, BCVA was 67.69&#xa0;&#xb1;&#xa0;10.89 letters at baseline and 65.38&#xa0;&#xb1;&#xa0;10.34 letters at last follow-up. The mean follow-up was 258.46&#xa0;&#xb1;&#xa0;97.54 days. In both groups, no statistically significant difference was observed between the baseline and final BCVA. For treated eyes, the mean annualized growth rate (square root) was 0.275&#xa0;mm and for nontreated eyes it was 0.321&#xa0;mm. The annualized growth rate of the hyperTDs in treated eyes was 14.5% lower than that in nontreated eyes (P&#xa0;= 0.007). No adverse events were recorded.<br><br>CONCLUSIONS: These preliminary data suggest that intravitreal CB-PRP injections might be safe and effective in slowing the progression of atrophy in AMD. Extended follow-up and larger sample sizes are needed to confirm our findings and determine the optimal treatment regimen for this novel treatment option in late-stage dry AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40212931,
year = {2025},
author = {Stein, JD and An, HS and Andrews, CA and Pershing, S and Mungle, T and Bicket, AK and Rosenthal, JM and Zhang, AD and Lee, WS and Ludwig, C and Mekonnen, B and Hernandez-Boussard, T and , },
title = {Enhanced Phenotype Identification of Common Ocular Diseases in Real-World Datasets.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100717},
pmid = {40212931},
issn = {2666-9145},
abstract = {OBJECTIVE: For studies using real-world data, accurately identifying patients with phenotypes of interest is challenging. To identify cohorts of interest, most studies exclusively use the International Classification of Diseases (ICD) billing codes, which can be limiting. We developed a method to accurately identify the presence or absence of 3 common ocular diseases (diabetic retinopathy [DR], age-related macular degeneration [AMD], and glaucoma) using electronic health record (EHR) data.<br><br>DESIGN: Database study.<br><br>PARTICIPANTS: Three thousand nine hundred fourteen eyes from 1957 patients at 2 Sight OUtcomes Research CollaborativE (SOURCE) Ophthalmology Data Repository sites.<br><br>METHODS: We developed enhanced phenotype identification (EPI) algorithms that search EHR fields, including eye examination findings, orders, charges, medication prescriptions, and surgery data for evidence that a patient has glaucoma, DR, or AMD. We trained our EPI models using gold standard assessments of the EHR by ophthalmologists for the presence/absence of these conditions, compared the performance of our EPI models to models developed using ICD codes alone, and validated the performance of model using data from another SOURCE site.<br><br>MAIN OUTCOME MEASURES: Area under the receiver operating curve (AUC), area under the precision-recall curve (AUPRC), and model calibration.<br><br>RESULTS: The AUCs of our EPI models were better than ICD-only models for glaucoma (0.97 vs. 0.90), DR (0.997 vs. 0.98), and AMD (0.99 vs. 0.95). The AUPRCs of our EPI models were also much better than ICD-only models for glaucoma (0.79 vs. 0.32), DR (0.96 vs. 0.84), and AMD (0.74 vs. 0.55). When testing on patients from a second SOURCE site, the AUC and AUPRC for glaucoma (0.93, 0.74), DR (0.98, 0.77), and AMD (0.96, 0.64) were slightly worse than the primary site but still quite high. However, for all 3 conditions, model calibration was worse at the second site.<br><br>CONCLUSIONS: Leveraging machine learning, we developed EPI models to accurately identify most patients with glaucoma, DR, and AMD in real-world datasets. The EPI models significantly outperform ICD-only models in identifying patients confirmed to have these conditions. These findings underscore the potential of using comprehensive EHR data combined with advanced machine learning techniques to improve the accuracy of patient phenotype identification, leading to better patient management and clinical outcomes.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40212928,
year = {2025},
author = {Bugg, VA and Eppich, K and Blakley, MS and Lum, F and Greene, T and Hartnett, ME},
title = {Vision Loss and Blindness in the United States: An Age-Adjusted Comparison by Sex and Associated Disease Category.},
journal = {Ophthalmology science},
volume = {5},
number = {4},
pages = {100735},
pmid = {40212928},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate differences in vision loss and blindness by disease category between men and women in the the United States (US).<br><br>DESIGN: Retrospective observational study.<br><br>PARTICIPANTS: Patients (14 549 105) >50 years old with eye examination data recorded in the American Academy of Ophthalmology IRIS&#xae; Registry (Intelligent Research in Sight) between January 1, 2018, and December 31,&#xa0;2018.<br><br>METHODS: Patients were assigned to the vision loss cohort and categorized (mild, moderate, severe, blindness) based on the best-corrected visual acuity in the better-seeing eye. The cause of vision loss was assumed using the International Classification of Diseases, 10th Revision codes for cataract, diabetic retinopathy, age-related macular degeneration (AMD), glaucoma, retinal detachment, retinal vein occlusion, corneal opacity, or amblyopia documented in the electronic health record. The no vision loss cohort was created by subtracting the vision loss cohort from the 2018 total IRIS Registry database.<br><br>MAIN OUTCOME MEASURES: Primary analyses provided age-adjusted prevalence ratios (PRs) for vision loss conditions for women and men within the vision loss cohort relative to the 2018 US census. Secondary analyses computed age-adjusted PRs for women and men for the same conditions relative to the IRIS Registry.<br><br>RESULTS: The age-adjusted PR of vision loss in women versus men when comparing our vision loss cohort relative to the US census was 1.28 (95% confidence interval, 1.27, 1.29) for mild vision loss, 1.29 (1.28, 1.30) for moderate vision loss, 1.35 (1.32, 1.38) for severe vision loss, and 1.54 (1.49, 1.59) for blindness. However, these differences were attenuated when age-adjusted prevalences were computed relative to those who were seen in 2018 in the IRIS Registry database. In women, the prevalence of vision loss associated with cataract and AMD was increased in both analyses, while men had a higher prevalence of vision loss associated with retinal detachment in both analyses.<br><br>CONCLUSIONS: Women in the US are more likely to be diagnosed with vision loss at an IRIS Registry practice compared with men, based on clinical presentations relative to the US census. However, this finding is partly driven by the higher rates at which women presented to ophthalmic practices in both the vision loss cohort and no vision loss cohort. The age-adjusted prevalence for vision loss associated with cataract and AMD was higher in women when utilizing both the US census and the 2018 IRIS Registry database as the denominator, which suggests that a true difference in prevalence is present. The&#xa0;same is true for an increase in the age-adjusted relative risk for vision loss associated with retinal detachment in men. These findings warrant further study.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40212557,
year = {2024},
author = {Chou, SJ and Yang, YP and Chiang, MR and Chen, CY and Lai, HIAM and Lin, YY and Wu, YR and Wang, IC and Yarmishyn, AA and Chiou, GY and Lin, TC and Hwang, DK and Chen, SJ and Chien, Y and Hu, SH and Chiou, SH},
title = {Ophthalmic Tethered Gold Yarnball-Mediated Retained Drug Delivery for Eye Fundus Disease Treatment.},
journal = {Small science},
volume = {4},
number = {8},
pages = {2400095},
pmid = {40212557},
issn = {2688-4046},
abstract = {Eye fundus diseases, such as retinal degenerative diseases, which lead to blindness in ≈12% of individuals aged >65 years, cause permanent damage to retinal cells. The antioxidant quercetin (QC) is promising for the effective treatment of eye fundus diseases; however, its poor solubility and low retention rate often limit its clinical application. Herein, an in situ ophthalmic tethered gold yarnball (GY) that doubles as an ocular retention agent and QC reservoir to overcome low fundus drug retention is developed. After intravitreal injection, QC@GYs enhance retinal cell leakage and internal limiting membrane permeability, facilitating the partial penetration of QC@GYs into the intraretinal tissue. The combination of retina-tethered QC@GY and first-level sustained release reduces macular degeneration in vivo by effectively regulating oxidative stress. Furthermore, the sustained release of QC preserves the viability of retinal pigment epithelium cells, reduces apoptosis, and suppresses drusen formation. This preservation of retinal morphology and function maximizes the therapeutic impact while minimizing the need for frequent intraocular administration. Overall, the ophthalmic tethered GY platform is a versatile tool for retinal drug delivery for the treatment of eye fundus diseases.},
}
@article {pmid40211932,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Xu, J and Wei, WB and Wang, YX},
title = {Macular ridges: Prevalence and associated factors-The Beijing Eye Study.},
journal = {Acta ophthalmologica},
volume = {103},
number = {8},
pages = {1058-1066},
doi = {10.1111/aos.17494},
pmid = {40211932},
issn = {1755-3768},
support = {82271086//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Prevalence ; Male ; Female ; *Tomography, Optical Coherence/methods ; Middle Aged ; Beijing/epidemiology ; Adult ; Axial Length, Eye/pathology ; Aged ; *Macula Lutea/pathology ; *Myopia/epidemiology/diagnosis/physiopathology ; Risk Factors ; *Visual Acuity ; China/epidemiology ; Cross-Sectional Studies ; *Population Surveillance ; },
abstract = {PURPOSE: To explore the prevalence and associated factors of macular ridges in a population-based study sample.<br><br>METHODS: From the participants of the population-based Beijing Eye Study (n&#x2009;=&#x2009;3468), we included all eyes with an axial length of &#x2265;25&#x2009;mm and a randomized sample of the remaining myopic eyes. Using optical coherence tomographic images, we assessed the prevalence and height of macular ridges, defined as an elevation of the foveal region in one meridian.<br><br>RESULTS: Among 366 study eyes, 50 (13.7%; 95% CI: 10.1, 17.2) showed macular ridges. Macular ridge prevalence increased from 0/78 (0%) in the group with an axial length of &#x2264;23&#x2009;mm to 18/71 (25.4%), 7/27 (25.9%) and 15/29 (51.7%) in axial length groups of 26-26.99&#x2009;mm, 27-27.99&#x2009;mm and &#x2265;28&#x2009;mm, respectively. Higher macular ridge prevalence was associated (multivariable analysis) with longer axial length (OR: 1.79; 95% CI: 1.48, 2.16; p&#x2009;<&#x2009;0.001) and older age (OR: 1.08; 95% CI: 1.04, 1.12; p&#x2009;<&#x2009;0.001). Macular ridge height (mean:128&#x2009;&#xb1;&#x2009;79&#x2009;&#x3bc;m) increased with longer axial length (0.31; B: 7.84; 95% CI: 5.39, 10.3; p&#x2009;<&#x2009;0.001) and older age (beta: 0.16; B: 0.88; 95% CI: 0.34, 1.42; p&#x2009;<&#x2009;0.001). Macular ridge orientation was most often in the horizontal meridian (28/50 eyes; 56%), followed by the vertical meridian (9/50 eyes; 18%) and the 7 o'clock-to-1 o'clock meridian (8/50 eyes; 16%). It was not significantly (p&#x2009;=&#x2009;0.17) associated with the axis of cylindrical corneal refractive error.<br><br>CONCLUSIONS: Macular ridges were relatively common in myopic eyes, with macular ridge prevalence and height increasing with longer axial length and older age in a curvilinear manner. They were not significantly associated with corneal astigmatism or best-corrected visual acuity. They may be explained by an inter-plane asymmetry in axial elongation-associated enlargement of Bruch's membrane in the fundus midperiphery.},
}
@article {pmid40211198,
year = {2025},
author = {Montrimas, A and Rinkevičiūtė, J and Žemaitienė, R},
title = {Posterior capsule opacification treatment using Nd: YAG laser capsulotomy: 36 months retrospective analysis.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {197},
pmid = {40211198},
issn = {1471-2415},
mesh = {Humans ; Retrospective Studies ; Female ; *Capsule Opacification/surgery ; Male ; *Lasers, Solid-State/therapeutic use ; Aged ; Visual Acuity ; *Posterior Capsulotomy/methods ; Middle Aged ; *Laser Therapy/methods ; Aged, 80 and over ; Follow-Up Studies ; Risk Factors ; Lens Implantation, Intraocular ; },
abstract = {BACKGROUND: The study aimed to identify factors influencing the time from cataract surgery to PCO treatment with Neodymium: Yttrium-Aluminium-Garnet (Nd: YAG) laser.<br><br>METHODS: For PCO risk factors analysis the retrospective study included 1045 eyes treated for PCO using Nd: YAG laser capsulotomy in the Hospital of Lithuanian University of Health Sciences (HLUHS) Kaunas Clinics with reduced best-corrected distance visual acuity (BCDVA) and opacity in the central 3&#xa0;mm zone. Eyes with no comorbidities were categorized into groups according to the intraocular lense (IOL) implanted and the time from cataract operation to Nd: YAG capsulotomy was compared. Tests used for statistical analysis: Shapiro-Wilk, Kruskal-Wallis, Mann-Whitney, one-way independent ANOVA, Pearson's or Spearman's correlation coefficient, and multivariable linear regression.<br><br>RESULTS: A total of 918 patients (1045 eyes) were included. The median time from cataract surgery to capsulotomy was 39.0 (27.4-54.6) months (min. 2; max. 174), did not differ between men and women, and was shorter for junior surgeons (25.8 (19.8-35.1) months) compared to senior surgeons (39.6 (27.8-55.3) months) (p&#x2009;<&#x2009;0.001). Seven factors affecting the time from cataract surgery to Nd: YAG capsulotomy were found: IOL model, surgeon's experience, BCDVA after surgery, capsular tension ring, pseudoexfoliation, BCDVA before capsulotomy and exudative age-related macular degeneration (adjusted R[2]&#x2009;=&#x2009;0.452; p&#x2009;<&#x2009;0.001). The IOL model was the only factor with a strong correlation. The median time from cataract surgery to capsulotomy differed between all IOL groups: Acriva UD613 group 31.5 (23.0-38.0) months, Johnson&amp;Johnson Tecnis ZCB00 group 41.0 (33.5-66.5) months, Bausch&amp;Lomb Envista MX60 group 45.0 (38.5-54.5) months, and Alcon Acrysof IQ SN60WF group 53.0 (41.5-79.5) months.<br><br>CONCLUSIONS: The IOL model seems to have the greatest influence on the time from cataract surgery to Nd: YAG capsulotomy. Acrylic hydrophobic IOLs with a square optical edge have different times from cataract surgery to Nd: YAG capsulotomy. Hydrophobic acrylic IOL seems to have a longer time from cataract surgery to Nd: YAG capsulotomy compared to hydrophilic acrylic IOL with a hydrophobic surface.},
}
@article {pmid40211016,
year = {2025},
author = {Kim, SB and Shaia, JK and Kaelber, DC and Singh, RP and Talcott, KE},
title = {Ocular manifestations in Ehlers-Danlos syndrome.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {1990-1997},
pmid = {40211016},
issn = {1476-5454},
support = {UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1TR002548//U.S. Department of Health &amp; Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; UM1 TR004528/TR/NCATS NIH HHS/United States ; P30EY025585(BA-A)//Research to Prevent Blindness (RPB)/ ; P30 EY025585/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Ehlers-Danlos Syndrome/epidemiology/complications/diagnosis ; Female ; Cross-Sectional Studies ; Male ; Adult ; Adolescent ; Middle Aged ; Child ; Young Adult ; *Eye Diseases/epidemiology/etiology/diagnosis ; Infant ; Child, Preschool ; Prevalence ; Infant, Newborn ; United States/epidemiology ; Aged ; Age Distribution ; Sex Distribution ; Retrospective Studies ; },
abstract = {BACKGROUND/OBJECTIVE: To provide a large-scale analysis on the demographics and ocular comorbidities in Ehlers-Danlos Syndrome (EDS) patients in the US.<br><br>SUBJECTS/METHODS: This is an exploratory cross-sectional study comparing medical records of EDS patients to the general population on demographic variables and ICD-10 ocular diagnoses. A research platform with de-identified EHR data of over 99 million patients across 60 healthcare organizations was utilized. Groups were stratified by 30-year age groups. Patients aged 0-61+ with an ICD-10 diagnosis of EDS (76,526), the general platform population aged 0-61+ (99,836,639), and patients with a concurrent ICD-10 ocular diagnosis were queried to determine the prevalence of EDS across demographic variables, ocular disease, and odds of ocular disease. Statistical analysis was conducted using Microsoft Excel and R studio, using p&#x2009;<&#x2009;0.01 and 95% confidence intervals (CI).<br><br>RESULTS: An EDS diagnosis was most prevalent in white females aged 0-30 years old (259.6 per 100,000). The majority of ocular diagnoses were more prevalent in the 0-60-year-old EDS population compared to the general population including myopia (5227.0 per 100,000) and dry eye (4211.6 per 100,000). Overall, diagnoses of angioid streaks (POR 18.72, 95% CI 10.32, 33.94) and idiopathic intracranial hypertension (IIH) (POR 18.43, 95% CI 17.51, 19.39) showed the highest increased odds in patients with EDS while significantly decreased odds were shown for type 2 diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion.<br><br>CONCLUSIONS: EDS was associated with increased odds of having a concurrent ocular pathology, suggesting that, upon diagnosis of EDS, referral to ophthalmology may be valuable.},
}
@article {pmid40210893,
year = {2025},
author = {Cheng, SY and Giguere, D and Silverstein, I and Conza, A and Seddon, JM and Kim, S and Iwata, T and Mueller, C and Punzo, C},
title = {Role of alpha-1 antitrypsin in Bruch's membrane integrity.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {12223},
pmid = {40210893},
issn = {2045-2322},
support = {EY028602/EY/NEI NIH HHS/United States ; EY032461/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; M2020016//BrightFocus Foundation/ ; R01 EY032461/EY/NEI NIH HHS/United States ; },
mesh = {*Bruch Membrane/metabolism/pathology ; Animals ; *alpha 1-Antitrypsin/metabolism/genetics ; Humans ; Mice ; *Macular Degeneration/metabolism/pathology/genetics ; Mice, Knockout ; Retinal Pigment Epithelium/metabolism ; Laminin/metabolism ; Elastin/metabolism ; Male ; Collagen/metabolism ; Mice, Inbred C57BL ; Female ; Complement Factor H/metabolism ; },
abstract = {Alpha-1 antitrypsin (AAT) is a serine protease inhibitor that plays a crucial role in maintaining extracellular matrix integrity. Studies suggest that AAT augmentation therapy may benefit multiple eye diseases, including age-related macular degeneration (AMD). However, the function of endogenous AAT in the eye remains unclear. Here we used genetic knockout mice to study the role of AAT in eye health. We show that loss of AAT results in Bruch's membrane (BrM) thickening driven in part by increased laminin deposition with a concomitant decrease in collagen and elastin, which are two other critical BrM components. Interestingly, BrM remodeling due to excess extracellular protease activity reduced the age-related deposition at the BrM of apolipoprotein E, while increasing complement factor H and lowering secretion of the proangiogenic vascular endothelial growth factor. Despite these changes, the phagocytic function of the retinal pigment epithelium was not affected nor was the expression of genes that partake in photoreceptor cell metabolism. Consistent with loss of AAT resulting in changes that should alleviate AMD pathologies, human AMD donor eyes exhibited lower AAT expression levels in the BrM/choroid layer when compared to healthy donor eyes. Together, the study provides insight into AAT's function and its potential involvement in AMD.},
}
@article {pmid40210713,
year = {2025},
author = {Gutfleisch, M and Heimes-Bussmann, B and Aydin, S and Petrovic, R and Loktyushin, A and Ohji, M and Takahashi, K and Okada, AA and Scholz, P and Youssef, H and Bauer-Steinhusen, U and Machewitz, T and Rothaus, K and Lommatzsch, A},
title = {A post-hoc analysis of intravitreal aflibercept-treated nAMD patients from ARIES &amp; ALTAIR: predicting treatment intervals and frequency for aflibercept treat-and-extend therapy regimen using machine learning.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {7},
pages = {1885-1897},
pmid = {40210713},
issn = {1435-702X},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Intravitreal Injections ; *Machine Learning ; *Wet Macular Degeneration/drug therapy/diagnosis ; Female ; Male ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Treatment Outcome ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Fluorescein Angiography ; Time Factors ; ROC Curve ; Macula Lutea/pathology ; },
abstract = {PURPOSE: To predict potential treatment need during treat-and-extend (T&amp;E) anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD) using an artificial intelligence (AI) model trained using transfer learning.<br><br>METHODS: ARIES and ALTAIR were randomized controlled Phase 3b/4 trials assessing intravitreal aflibercept (IVT-AFL) in patients with nAMD. Following treatment initiation with three monthly injections of IVT-AFL, treatment intervals were re-assessed continuously during the study based on prespecified criteria. In this post- hoc analysis, spectral domain optical coherence tomography (SD-OCT) scans from Week (Wk) 8 and Wk 16 visits from patients treated with T&amp;E regimens of 2&#xa0;mg IVT-AFL over 2&#xa0;years were utilized to predict individual treatment intervals and frequency. Automated image segmentation of the SD-OCT scans was performed, predictive models of treatment intervals and frequency were developed using machine learning or logistic regression methods, and their performance was evaluated using a fivefold cross-validation. A transfer learning technique was used to adapt existing AI models previously trained on a pro-re-nata therapy regimen to the T&amp;E dataset.<br><br>RESULTS: In total, 205 ARIES and 112 ALTAIR patient datasets were used for training and evaluation. The following results were achieved with an AI model trained using transfer learning (for ARIES) and logistic regression (for ALTAIR). For prediction of the first treatment interval (short [<&#x2009;12&#xa0;weeks] or long [&#x2265;&#x2009;12&#xa0;weeks]) following treatment initiation, at Visit 4 (Wk 16), the AI model achieved an area under the receiver operating characteristic curve (AUC) of 0.87 and 0.78 for ARIES and ALTAIR, respectively. For assessment of the individual frequency of IVT-AFL in the first and second study years, the model achieved an AUC of 0.84 and 0.79, respectively, for ARIES, and 0.79 and 0.78, respectively, for ALTAIR. For prediction of the last intended individual treatment interval at the end of Year 2, the AI model achieved an AUC of 0.74 and 0.77 for ARIES and ALTAIR, respectively.<br><br>CONCLUSION: AI trained using transfer learning can be used to predict potential treatment needs for anti-VEGF treatment in nAMD based on SD-OCT scans at Wk 8 and Wk 16, supporting medical decisions on interval adjustments and optimizing individualized IVT-AFL treatment regimens.},
}
@article {pmid40205682,
year = {2025},
author = {Bammidi, S and Ghosh, S and Chowdhury, O and Babu, VS and Dutta, P and Hose, S and Sinha, D},
title = {MLST8 overexpression in RPE cells disrupts autophagy through novel mechanisms affecting AMD pathogenesis.},
journal = {Autophagy},
volume = {21},
number = {8},
pages = {1856-1858},
pmid = {40205682},
issn = {1554-8635},
mesh = {*Autophagy/genetics ; Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/pathology/metabolism/genetics ; Mice ; Humans ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Autophagosomes/metabolism ; TOR Serine-Threonine Kinases/metabolism ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Disease Models, Animal ; Lysosomes/metabolism ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Mice, Inbred C57BL ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, with dysfunction of the retinal pigment epithelium (RPE) central to disease pathogenesis. Using our uniquely developed MLST8 (MTOR associated protein, LST8 homolog) knock-in animal model with RPE-specific overexpression, which drives MTOR (mechanistic target of rapamycin kinase) upregulation, we demonstrate that increased MTOR complexes 1 and 2 in the RPE disrupts macroautophagy/autophagy by suppressing autophagosome formation genes and impairing MAP1LC3/LC3 processing. This leads to autophagosome accumulation and defective autolysosome formation, driving RPE dysfunction and AMD-like pathology, including subretinal debris build up and photoreceptor degeneration. Notably, MTOR inhibition with torin1 treatment or CRYBA1 overexpression rescues these defects, restoring autophagy and RPE integrity. Our findings reveal that autophagy disruption mediated by both MTORC1 and MTORC2 drives AMD-like pathology in our mouse model, establishing autophagy regulation as a promising avenue for therapeutic intervention in this vision-threatening disease.},
}
@article {pmid40204251,
year = {2025},
author = {Cao, C and Liu, M and Yuan, L and Yu, H and Guo, S and Su, S and Kang, H and Duan, JA and Zhu, Y},
title = {Lycii Fructus and Chrysanthemum Flos, a Chinese medicine herbal pair, ameliorates retinal degeneration of mice induced by sodium iodate and protects Müller cells from oxidative stress.},
journal = {Journal of ethnopharmacology},
volume = {347},
number = {},
pages = {119747},
doi = {10.1016/j.jep.2025.119747},
pmid = {40204251},
issn = {1872-7573},
mesh = {Animals ; *Chrysanthemum/chemistry ; *Oxidative Stress/drug effects ; *Ependymoglial Cells/drug effects/metabolism/pathology ; Iodates/toxicity ; *Lycium/chemistry ; Mice ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Apoptosis/drug effects ; NF-E2-Related Factor 2/metabolism ; *Retinal Degeneration/chemically induced/drug therapy/pathology/metabolism ; *Macular Degeneration/drug therapy/chemically induced/pathology ; Plant Extracts/pharmacology ; Flowers ; Retina/drug effects/pathology/metabolism ; Fruit ; },
abstract = {The combination of Lycii Fructus (LF) and Chrysanthemum Flos (CF) is a well-known herbal pair utilized in Chinese medicine for the treatment of retinal degeneration diseases commonly found in the elderly, such as age-related macular degeneration (AMD). However, the precise mechanisms of action mechanism and active constituents responsible for the therapeutic effects of the LF-CF herbal pair in improving AMD remain unknown.<br><br>AIM OF THE STUDY: This study aims to evaluate the effect of the LF-CF herbal pair on alleviating retinal damage and apoptosis in M&#xfc;ller cells of a dry AMD mouse model, especially its role in enhancing oxidative stress in the retina. Moreover, it endeavors to clarify the underlying action mechanisms and identify the bioactive ingredients in the LF - CF herbal pair that act on M&#xfc;ller cells to alleviate oxidative stress.<br><br>MATERIALS AND METHODS: A mice model of dry AMD was established through intraperitoneal administration of sodium iodate. Various solvents were employed to prepare extracts of the LF-CF herbal pair. The impact of these solvent extracts on ameliorating oxidative damage and determination of oxidation index in the retina was assessed. The ability of LF-CF herbal pair on regulating Nrf2/HO-1 signaling pathway in model mice was also detected. The MIO-M1 cell cultures were employed to assess the impact of extracts on protecting cells from oxidative damage caused by sodium iodate. The cell cultures were also utilized to investigate the potential mechanism of action and identify the active components involved.<br><br>RESULTS: The LF-CF herbal pair extracts showed evident protective effects on the mouse retina against sodium iodate-induced oxidative damage. They maintained retinal structural integrity and inhibited apoptosis. Among the extracts, the aqueous and 70&#xa0;% ethanol ones were more effective in preventing retina injury. These two extracts enhanced antioxidant enzyme activity, reduced oxidative products in the experimental mice's retina, reversing the down-regulation of glutamine synthetase (a M&#xfc;ller cell marker). In vitro, the aqueous and 70&#xa0;% ethanol extracts of the LF-CF herbal pair also protected MIO-M1 cells from sodium iodate-induced oxidative stress via regulating caspase-dependent and Nrf2/HO-1 signaling pathways. Lycium barbarum polysaccharides and luteolin are likely the active ingredients responsible for these effects.<br><br>CONCLUSIONS: The LF-CF herbal pair demonstrated the ability to mitigate oxidative stress in the retina and suppress apoptosis in M&#xfc;ller cells through the regulation of caspase-dependent and Nrf2/HO-1 signaling pathways. These findings contribute to the growing body of scientific evidences supporting the potential of LF-CF herbal pair as a viable therapeutic option or preventive measure for dry AMD.},
}
@article {pmid40204187,
year = {2025},
author = {Suimon, Y and Nishimura, M and Murata, M and Yoshida, S and Yokoi, K and Dong, Z and Kuno, N and Fujii, S and Tanei, ZI and Yabe, I and Noda, K and Ishida, S},
title = {Leucine-Rich Repeat Kinase 2 Promotes Disintegration of Retinal Pigment Epithelial Cell: Implication in the Pathogenesis of Dry Age-Related Macular Degeneration.},
journal = {The American journal of pathology},
volume = {195},
number = {7},
pages = {1294-1310},
doi = {10.1016/j.ajpath.2025.03.002},
pmid = {40204187},
issn = {1525-2191},
mesh = {Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; *Retinal Pigment Epithelium/pathology/enzymology/metabolism ; Animals ; Mice ; Mice, Transgenic ; *Protein Serine-Threonine Kinases/metabolism/genetics ; alpha-Synuclein/metabolism ; *Macular Degeneration/pathology/enzymology ; Apoptosis ; Aged ; Cell Line ; Phosphorylation ; Female ; *Geographic Atrophy/pathology/enzymology ; },
abstract = {Recent epidemiologic studies have shown that patients with age-related macular degeneration (AMD) have a considerably higher risk of developing Parkinson disease (PD) later in life, suggesting a possible link between these diseases. However, the common mechanisms between these two diseases remain obscure, although the pathophysiology of each has been well investigated. This study was designed to explore the shared pathologic features of AMD and PD by focusing on leucine-rich repeat kinase 2 (LRRK2) and α-synuclein, both of which play crucial roles in PD pathogenesis. Immunohistochemistry for LRRK2 and α-synuclein was performed on human eye specimens. The effect of LRRK2 on retinal pigment epithelium (RPE) cell function was investigated using the RPE cell line hTERT-RPE1. Retinal morphology and function were examined in LRRK2-G2019S transgenic mice, representing mutants with increased kinase activity of LRRK2. Immunohistochemistry revealed that LRRK2 and α-synuclein were present in the RPE layer of the human eye. Overexpression of LRRK2 in RPE cells increased α-synuclein and induced cell death. LRRK2 inhibited α-synuclein degradation via phosphorylation of RAB, member RAS oncogene GTPases. LRRK2-G2019S transgenic mice exhibited apoptosis of RPE and photoreceptors, choroidal thinning, and reduced electroretinogram amplitude, on top of α-synuclein protein accumulation in the RPE cell layer. Taken together, the current study revealed that LRRK2 is one of the key molecules involved in the common pathologic mechanisms of AMD and PD.},
}
@article {pmid40202735,
year = {2025},
author = {Parekh, Z and Xiao, J and Mani, A and Evans, Q and Phung, C and Barba, HA and Xie, B and Sidebottom, AM and Sundararajan, A and Lin, H and Ramaswamy, R and Dao, D and Gonnah, R and Yehia, M and Hariprasad, SM and D'Souza, M and Sulakhe, D and Chang, EB and Skondra, D},
title = {Fecal Microbial Profiles and Short-Chain Fatty Acid/Bile Acid Metabolomics in Patients With Age-Related Macular Degeneration: A Pilot Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {21},
pmid = {40202735},
issn = {1552-5783},
support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; },
mesh = {Humans ; Pilot Projects ; Male ; Female ; *Feces/microbiology ; Aged ; *Gastrointestinal Microbiome/physiology ; Metabolomics/methods ; *Fatty Acids, Volatile/metabolism ; *Macular Degeneration/metabolism/microbiology ; *Bile Acids and Salts/metabolism ; Aged, 80 and over ; RNA, Ribosomal, 16S/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Bacteria/genetics/isolation &amp; purification ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease, and studies have implicated the role of gut microbiota in its pathogenesis. However, characterization of microbiome dysbiosis and associated microbial-derived metabolomic profiles across AMD stages remains unknown. In this pilot study, we explored how gut microbiome composition and gut-derived metabolites differ in AMD.<br><br>METHODS: Our pilot study analyzed fasted stool samples that were collected from 22 patients at a tertiary academic center. Subjects were classified as control, intermediate AMD, or advanced AMD based on clinical presentation. 16S rRNA amplicon sequencing and standard chromatography-mass spectrometry methods were used to identify bacterial taxonomy composition and abundance of short-chain fatty acids (SCFAs) and bile acids (BAs), respectively. Genetic testing was used to investigate the frequency of 14 high-risk single nucleotide polymorphisms (SNPs) associated with AMD in the AMD cohort.<br><br>RESULTS: Forty-three differentially abundant genera were present among the control, intermediate, and advanced groups. Taxa with known roles in immunologic pathways, such as Desulfovibrionales (q = 0.10) and Terrisporobacter (q = 1.16e-03), were in greater abundance in advanced AMD patients compared to intermediate. Advanced AMD patients had decreased abundance of 12 SCFAs, including acetate (P = 0.002), butyrate (P = 0.04), and propionate (P = 0.01), along with 12 BAs, including taurocholic acid (P = 0.02) and tauroursodeoxycholic acid (P = 0.04). Frequencies of high-risk SNPs were not significantly different between the intermediate and advanced AMD groups.<br><br>CONCLUSIONS: This pilot study identifies distinct gut microbiome compositions and metabolomic profiles associated with AMD and its stages, providing preliminary evidence of a potential link between gut microbiota and AMD pathogenesis. To validate these findings and elucidate the underlying mechanisms, future research with larger cohorts and more comprehensive sampling is strongly recommended.},
}
@article {pmid40201446,
year = {2025},
author = {Venter, JA and Berry, CW and Hannan, NC and Raju, D and Kiss, HJ and Belovari, M and Hannan, SJ and Cooper, DR and Schallhorn, JM},
title = {Clinical Outcomes of an Enhanced and Conventional Monofocal IOL in Patients with Early and Intermediate Dry Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1203-1214},
pmid = {40201446},
issn = {1177-5467},
abstract = {PURPOSE: To compare the performance of an enhanced and conventional monofocal IOL in eyes with early and intermediate age-related macular degeneration (AMD).<br><br>METHODS: This retrospective study compared one-month postoperative outcomes of patients bilaterally implanted with TECNIS Eyhance IOL (ICB00 group) or TECNIS Monofocal IOL (ZCB00 group). All patients underwent cataract surgery with pre-existing early or intermediate dry AMD. Outcome measures were monocular and binocular uncorrected distance (UDVA), intermediate (UIVA) and near (UNVA) visual acuity, monocular corrected distance visual acuity (CDVA), and refractive outcomes. Monocular visual acuities and refractive predictability were calculated for the dominant eye of each patient.<br><br>RESULTS: The ICB00 group comprised 143 eyes of 143 patients, while 164 eyes of 164 patients were included in the ZCB00 group. Preoperative characteristics were comparable between the two groups. There was no significant difference in postoperative refractive predictability, with 87.4% and 89.6% of eyes within 0.50 D of emmetropia in the ICB00 and ZCB00 groups, respectively (p=0.54). No difference was found in postoperative UDVA or CDVA between the groups. Both monocular and binocular UIVA were significantly better in the ICB00 group (monocular UIVA: 0.32&#xb1;0.19 vs 0.42&#xb1;0.22 logMAR, p<0.001; binocular UIVA: 0.25&#xb1;0.18 vs 0.36&#xb1;0.17 logMAR, p<0.001). Postoperative UNVA was also better with the ICB00 IOL (monocular UNVA: 0.58&#xb1;0.16 vs 0.69&#xb1;0.20 logMAR, p<0.001; binocular UNVA: 0.50&#xb1;0.16 vs 0.63&#xb1;0.17 logMAR, p<0.001).<br><br>CONCLUSION: ICB00 IOL enhanced intermediate and near vision in patients with AMD while achieving the same level of corrected and uncorrected distance visual acuity.},
}
@article {pmid40200344,
year = {2025},
author = {Wang, M and Zhang, X and Li, D and Wei, Q and Zhao, J and Gao, X and Shan, T and Feng, H and Ding, G and Li, C and Wu, B and Li, X and Wu, C and Yu, W},
title = {The potential of artificial intelligence reading label system on the training of ophthalmologists in retinal diseases, a multicenter bimodal multi-disease study.},
journal = {BMC medical education},
volume = {25},
number = {1},
pages = {503},
pmid = {40200344},
issn = {1472-6920},
support = {2022-PUMCH-C-061//National High Level Hospital Clinical Research Funding/ ; 2022-PUMCH-C-061//National High Level Hospital Clinical Research Funding/ ; },
mesh = {Humans ; *Artificial Intelligence ; *Retinal Diseases/diagnosis/diagnostic imaging ; Tomography, Optical Coherence ; *Ophthalmologists/education ; *Ophthalmology/education ; },
abstract = {OBJECTIVE: To assess the potential of artificial intelligence reading label system on the training of ophthalmologists in a multicenter bimodal multi-disease study.<br><br>METHODS: The accuracy of 16 ophthalmologists with study duration ranging from one to nine years across multiple annotation rounds and its correlation with the number of rounds and ophthalmology study duration were analyzed. Additionally, this study evaluated the concordance between optical coherence tomography (OCT) or color fundus photography (CFP) and final case diagnosis.<br><br>RESULTS: The study involved 7777 pairs of OCT and CFP images, cases labeled with nine prevalent retinal diseases including diabetic retinopathy (DR, 2118 cases), retinal detachment (RD, 121 cases), retinal vein occlusion (RVO, 886 cases), dry age-related macular degeneration (dAMD, 549 cases), wet age-related macular degeneration (wAMD, 1023 cases), epiretinal membrane (ERM, 1061 cases), central serous retinopathy (CSC, 150 cases), macular schisis (MS, 128 cases), macular hole (MH, 86 cases) and normal fundus (1036 cases) were selected for further analysis. All images were assigned to 16 ophthalmologists over five rounds. The average diagnostic accuracy for the nine retinal diseases and normal fundus improved significantly across the five rounds (p&#x2009;=&#x2009;0.013) and is closely correlated to the duration of ophthalmology study (p&#x2009;=&#x2009;0.007). Furthermore, significant improvements were observed in the diagnostic accuracy of both OCT (p&#x2009;=&#x2009;0.028) and CFP (p&#x2009;=&#x2009;0.021) modalities as the number of rounds increased. Notably, OCT single modal diagnosis demonstrated higher consistency with the final diagnosis in cases of RD, ERM, MS, and MH compared to CFP, while CFP single modal diagnosis has higher consistency in DR, RVO and normal fundus.<br><br>CONCLUSION: The implementation of an artificial intelligence reading label system enhances the diagnostic accuracy of retinal diseases among ophthalmologists and holds potential for integration into future medical education.},
}
@article {pmid40200296,
year = {2025},
author = {Cattaneo, J and De Oliveira Figueiredo, EC and Montesel, A and Vermeirsch, S and Eandi, CM},
title = {Early real-world outcomes of intravitreal aflibercept 8 mg in treatment-Naïve neovascular AMD: AI-assisted fluid volume analysis.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {42},
pmid = {40200296},
issn = {2056-9920},
abstract = {BACKGROUND: This study was conducted as a retrospective, exploratory analysis to assess early anatomical and functional effects of intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (nAMD) in a small cohort of patients.<br><br>METHODS: This retrospective study was conducted at the Jules Gonin Eye Hospital in Lausanne, Switzerland, and included treatment-na&#xef;ve patients with nAMD. Patients received a minimum of two intravitreal injections (IVT) of aflibercept 8&#xa0;mg over a 3-month period. Key outcomes assessed were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), mean retinal thickness (RT), total fluid (TF) volume which was calculated as the sum of intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) volumes. These parameters were evaluated at baseline, month 1, and month 3 using the RetinAI Discovery[&#xae;] platform, an artificial intelligence-based analysis system.<br><br>RESULTS: 10 eyes of 10 patients were enrolled. Mean age was 77.7&#x2009;&#xb1;&#x2009;12.5 years. Comparative analysis between baseline, month 1, and month 3 revealed statistically significant reduction in CST, RT and TF volume, indicating a positive early response to treatment. One adverse event of intraocular inflammation (IOI) occurred in one patient (10%) after the second IVT injection. Treatment was subsequently interrupted, and IOI resolved with topical corticosteroids therapy.<br><br>CONCLUSION: Intravitreal aflibercept 8&#xa0;mg demonstrated early anatomical and functional improvements in nAMD treatment-na&#xef;ve patients after the first 3-months. The use of the AI-based analysis allowed for detailed and automated assessment of retinal changes, providing valuable insights into early treatment effects. Given the retrospective design and small cohort, further studies are warranted to assess long-term outcomes and the potential predictive value of early changes on long-term visual prognosis and safety.<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid40199756,
year = {2025},
author = {Kleefeldt, N and Kuehnel, S and Reiser, L and Goebel, W and Hillenkamp, J and William, A},
title = {[Morphological and functional changes of secondary macular neovascularization in central serous chorioretinopathy under anti-VEGF treatment].},
journal = {Die Ophthalmologie},
volume = {122},
number = {6},
pages = {442-452},
pmid = {40199756},
issn = {2731-7218},
mesh = {Humans ; Retrospective Studies ; *Central Serous Chorioretinopathy/drug therapy/complications/pathology/diagnosis ; Male ; Female ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Middle Aged ; Fluorescein Angiography ; Aged ; Visual Acuity/drug effects ; Intravitreal Injections ; *Choroidal Neovascularization/drug therapy/etiology/pathology/diagnosis ; *Retinal Neovascularization/drug therapy/etiology/pathology ; Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; Macula Lutea/pathology ; },
abstract = {BACKGROUND: Investigation of the morphological changes by optical coherence tomography angiography (OCT-A) and the development of visual acuity in secondary macular neovascularization (sMNV) in central serous chorioretinopathy (CCS) during anti-vascular endothelial growth factor (VEGF) treatment.<br><br>PATIENTS AND METHODS: Retrospective study of all treatment-na&#xef;ve eyes with respect to anti-VEGF treatment, in which sMNV in CCS was detected by fluorescein angiography (FA) and OCT&#x2011;A and which were treated at the University Eye Hospital W&#xfc;rzburg between July 2021 and the end of December 2022. All patients were treated according to a&#xa0;pro re nata injection regimen (PRN regimen) and followed up for 1 year.<br><br>RESULTS: In the study 20 eyes from 16&#xa0;patients with sMNV in CCS were included. Using FA the sMNV could be confirmed in 35% of cases and using OCT&#x2011;A in 100% of cases. Morphologically, the sMNV was clearly demarcated by OCT&#x2011;A as "sea-fan"-like in 10&#xa0;eyes and filamentous in 10&#xa0;eyes. The decrease in area of the sMNV from 0.94&#x202f;&#xb1;&#x2009;1.2&#x202f;mm[2] at baseline to 0.72&#x202f;&#xb1;&#x2009;0.82&#x202f;mm[2] at 12&#xa0;months was not statistically significant (p&#x202f;=&#x2009;0.12). During the observational period an average of 8.7&#x202f;&#xb1;&#x2009;1.6 intravitreal injections (IVOM) were administered (5-12 IVOM, median 9&#xa0;IVOM).<br><br>DISCUSSION: Both FA and OCT&#x2011;A were used to detect sMNV in CCS, with OCT&#x2011;A providing more reliable detection of sMNV than FA. With OCT&#x2011;A two different types of sMNV could be detected: 1) the "sea-fan" type and&#xa0;2) the filamentous MNV type. Within the first year of treatment sMNV in CCS requires a&#xa0;comparable number of IVOMs as the treatment of neovascular age-related macular degeneration.},
}
@article {pmid40199613,
year = {2025},
author = {Jones, L and Lee, M and Ditzel-Finn, L and Heinze, N and Dave, S and Tang, ESY and Potts, J and Moosajee, M and Gomes, RSM},
title = {Charles Bonnet syndrome among visually impaired military veterans: findings from a UK screening and survey study.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40199613},
issn = {2397-3269},
mesh = {Humans ; Male ; Female ; *Veterans/statistics &amp; numerical data ; Cross-Sectional Studies ; United Kingdom/epidemiology ; *Charles Bonnet Syndrome/epidemiology/diagnosis ; Prevalence ; Aged ; Aged, 80 and over ; *Persons with Visual Disabilities/statistics &amp; numerical data ; Visual Acuity/physiology ; Prospective Studies ; Middle Aged ; Vision Disorders/epidemiology ; Surveys and Questionnaires ; },
abstract = {BACKGROUND/AIMS: Charles Bonnet syndrome (CBS) is a common complication of visual impairment. However, demographic and clinical characteristics may modify the prevalence and impact of the condition. The aim was to investigate the prevalence of CBS among visually impaired military veterans and the associated impact of visual hallucinations.<br><br>METHODS: Cross-sectional screening and survey study of members at Blind Veterans UK, a national charity supporting ex-armed forces men and women with a registered visual impairment. Data were analysed using membership records followed by a prospective CBS screening measure and survey.<br><br>RESULTS: 461 military veterans with CBS were identified from 4109 individual records, representing 11.2% (95% CI 10.2% to 12.2%) of the population. From this, 115 members (24.9%) participated in the survey. The average age was 82.5 (&#xb1;12.3) years and 89.6% were male. The most common ophthalmic condition was age-related macular degeneration (58.3%) and participants had severely reduced visual acuity (average better eye 1.2 (&#xb1;1.4) LogMAR). Reporting 'bothersome' hallucinations was associated with living with CBS for over 3 years (p=0.01) and hallucinating at least once per week (p=0.05). Diverting attention elsewhere was considered an effective relief strategy among 64.9% (95% CI 56.2% to 73.6%) of those who had used this. Fewer than half (44.3%) had disclosed their symptoms to a hospital doctor and corresponding clinical management was variable.<br><br>CONCLUSION: CBS was common among visually impaired military veterans and was associated with negative outcomes. However, limitations include identifying cases through retrospective screening and not controlling for visual acuity and rehabilitation. Findings may not generalise beyond veterans in the charity's database. Yet, the findings yield evidence for a therapeutic benefit of relief strategies in managing symptoms and the need to promote dialogue about visual hallucinations between patients and clinicians.},
}
@article {pmid40199264,
year = {2025},
author = {De Geronimo, D and Parravano, M and Sacconi, R and Costanzo, E and Varano, M and Querques, G},
title = {Geographic Atrophy and Peripheral Atrophy: Quantitative Analysis with Ultra-Widefield Autofluorescence.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {248},
number = {3},
pages = {168-174},
doi = {10.1159/000544958},
pmid = {40199264},
issn = {1423-0267},
mesh = {Humans ; Male ; Female ; *Geographic Atrophy/diagnosis ; Aged ; *Fluorescein Angiography/methods ; Fundus Oculi ; *Tomography, Optical Coherence/methods ; Middle Aged ; *Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Atrophy ; *Visual Acuity ; Follow-Up Studies ; },
abstract = {INTRODUCTION: To analyze and correlate the topographic distribution of atrophic areas at the posterior pole and peripheral retina in subjects with geographic atrophy (GA) using ultra-widefield fundus autofluorescence (FAF) imaging.<br><br>METHODS: This multicenter observational study included 15 patients (9 males, 19 eyes) with coexisting GA and peripheral atrophy. All eyes were imaged with Ultra-widefield Optos California (Optos, PLC, Dunfermline, Scotland) to acquire ultra-widefield (200&#xb0;) color and FAF images centered on the fovea, superior, inferior, nasal, and temporal sectors. The extent of GA in the central FAF image and the peripheral atrophic areas in the peripheral FAF images were measured by manually defining the boundaries of the atrophic regions using the "ROI free" function integrated into the device software. The values obtained were then analyzed and correlated.<br><br>RESULTS: The mean &#xb1; standard deviation (SD) GA size was 13.9 &#xb1; 15.0 mm2 (range: 1.8-71.3 mm2) and the total peripheral atrophy was 51.0 &#xb1; 68.3 mm2 (range: 1.4-292.1 mm2). The topographic analysis showed that the mean &#xb1; SD of superior peripheral atrophy was 9.0 &#xb1; 20.6 mm2, temporal atrophy was 30.5 &#xb1; 55.9 mm2, inferior atrophy was 9.3 &#xb1; 16.3 mm2, and nasal atrophy was 1.8 &#xb1; 3.9 mm2. GA size was significantly correlated with total peripheral atrophy (Rho = 0.463, p = 0.046) and temporal peripheral atrophy (Rho = 0.474, p = 0.040), whereas no correlations were found with peripheral atrophy in the remaining sectors.<br><br>CONCLUSION: Ultra-widefield autofluorescence is a valuable technique for visualizing and assessing the extent of macular and peripheral atrophy. Macular atrophy correlates significantly with total and temporal peripheral atrophy but demonstrates no significant correlation with atrophy in the remaining sectors.},
}
@article {pmid40196674,
year = {2025},
author = {Li, H and Weiss, CE and Pandiyan, VP and Nanni, D and Liu, T and Kung, PW and Tan, B and Barathi, VA and Schmetterer, L and Sabesan, R and Ling, T},
title = {Optoretinography reveals rapid rod photoreceptor movement upon photoisomerization.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40196674},
issn = {2692-8205},
support = {L30 AI172024/AI/NIAID NIH HHS/United States ; L40 AI172024/AI/NIAID NIH HHS/United States ; R01 EY029710/EY/NEI NIH HHS/United States ; U01 EY032055/EY/NEI NIH HHS/United States ; },
abstract = {Rod photoreceptors are essential for vision under dim light conditions. The onset of rod-mediated vision is marked by the isomerization of rhodopsin. Here we demonstrate that human and rodent rods undergo a minute and rapid contraction of their outer segments immediately upon photoisomerization. The contraction is explained as an electro-mechanical manifestation of the rod early receptor potential generated in the disk membranes, which is challenging to access in electrophysiology. The bleach-strength dependence of the contraction was accounted by a voltage-dependent membrane tension model, developed earlier to explain a similar behavior in cones. The in vivo optical imaging of light-evoked electrical activity in rodent rods was facilitated by an ultrahigh-resolution point-scan optical coherence tomography (OCT) system coupled with unsupervised learning, while in humans, an adaptive optics line-scan OCT facilitated high-speed recordings in individual rods. The non-invasive in vivo optical imaging of rhodopsin activation will have a significant impact on diagnostics and treatment of retinal disease, especially given the vulnerability of rods in inherited and age-related macular degeneration.},
}
@article {pmid40196652,
year = {2025},
author = {Wang, SK and Li, J and Nair, S and Korasaju, R and Chen, Y and Zhang, Y and Kundaje, A and Liu, Y and Wang, N and Chang, HY},
title = {Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate pathogenic variants in age-related macular degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40196652},
issn = {2692-8205},
support = {RM1 HG007735/HG/NHGRI NIH HHS/United States ; T32 EY027816/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Genome-wide association studies (GWAS) of AMD have identified dozens of risk loci that may house disease targets. However, variants at these loci are largely noncoding, making it difficult to assess their function and whether they are causal. Here, we present a single-cell gene expression and chromatin accessibility atlas of human retinal pigment epithelium (RPE) and choroid to systematically analyze both coding and noncoding variants implicated in AMD. We employ HiChIP and Activity-by-Contact modeling to map enhancers in these tissues and predict cell and gene targets of risk variants. We further perform allele-specific self-transcribing active regulatory region sequencing (STARR-seq) to functionally test variant activity in RPE cells, including in the context of complement activation. Our work nominates new pathogenic variants and mechanisms in AMD and offers a rich and accessible resource for studying diseases of the RPE and choroid.},
}
@article {pmid40194867,
year = {2025},
author = {Srinivasan, S and Ji, H and Chen, DZ and Wong, W and Soh, ZD and Goh, JHL and Pushpanathan, K and Wang, X and Ma, W and Wong, TY and Wang, YX and Cheng, CY and Tham, YC},
title = {Can off-the-shelf visual large language models detect and diagnose ocular diseases from retinal photographs?.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40194867},
issn = {2397-3269},
mesh = {Humans ; *Eye Diseases/diagnosis ; *Photography/methods ; *Retina/pathology/diagnostic imaging ; *Artificial Intelligence ; Singapore/epidemiology ; Large Language Models ; },
abstract = {BACKGROUND: The advent of generative artificial intelligence has led to the emergence of multiple vision large language models (VLLMs). This study aimed to evaluate the capabilities of commonly available VLLMs, such as OpenAI's GPT-4V and Google's Gemini, in detecting and diagnosing ocular diseases from retinal images.<br><br>METHODS AND ANALYSIS: From the Singapore Epidemiology of Eye Diseases (SEED) study, we selected 44 representative retinal photographs, including 10 healthy and 34 representing six eye diseases (age-related macular degeneration, diabetic retinopathy, glaucoma, visually significant cataract, myopic macular degeneration and retinal vein occlusion). OpenAI's GPT-4V (both default and data analyst modes) and Google Gemini were prompted with each image to determine if the retina was normal or abnormal and to provide diagnostic descriptions if deemed abnormal. The outputs from the VLLMs were evaluated for accuracy by three attending-level ophthalmologists using a three-point scale (poor, borderline, good).<br><br>RESULTS: GPT-4V default mode demonstrated the highest detection rate, correctly identifying 33 out of 34 detected correctly (97.1%), outperforming its data analyst mode (61.8%) and Google Gemini (41.2%). Despite the relatively high detection rates, the quality of diagnostic descriptions was generally suboptimal-with only 21.2% of GPT-4V's (default) responses, 4.8% of GPT-4V's (data analyst) responses and 28.6% for Google Gemini's responses rated as good.<br><br>CONCLUSIONS: Although GPT-4V default mode showed generally high sensitivity in abnormality detection, all evaluated VLLMs were inadequate in providing accurate diagnoses for ocular diseases. These findings emphasise the need for domain-customised VLLMs and suggest the continued need for human oversight in clinical ophthalmology.},
}
@article {pmid40192800,
year = {2025},
author = {Andrades, U and Gaikar, S and Nathani, K and Sawarkar, S and Omri, A},
title = {Harnessing nanofibers for targeted delivery of phytoconstituents in age-related macular degeneration.},
journal = {Drug delivery},
volume = {32},
number = {1},
pages = {2489491},
pmid = {40192800},
issn = {1521-0464},
mesh = {*Nanofibers/chemistry/administration &amp; dosage ; Humans ; *Macular Degeneration/drug therapy ; *Drug Delivery Systems/methods ; *Phytochemicals/administration &amp; dosage/chemistry ; Animals ; },
abstract = {Age-related macular degeneration is a degenerative eye condition that affects the macula and results in central vision loss. Phytoconstituents show great promise in the treatment of AMD. AMD therapy can benefit from the advantages of phytoconstituents loaded nanofibers. There are opportunities to improve the effectiveness of phytoconstituents in the treatment of age-related macular degeneration (AMD) through the use of nanofiber-based delivery methods. These novel platforms encapsulate and distribute plant-derived bioactives by making use of the special qualities of nanofibers. These qualities include their high surface area-to-volume ratio, variable porosity, and biocompatibility. Exploring the use of nanofiber-based delivery methods to provide phytoconstituents in AMD treatment is a great choice for enhancing patient adherence, safety, and efficacy in managing this condition. This article explores the potential of nanofiber-based delivery methods to revolutionize AMD treatment, providing an innovative and effective approach to treat this condition.},
}
@article {pmid40191068,
year = {2025},
author = {Weng, PJ and Morgan, R and Grewal, DS and Fekrat, S},
title = {Possible Association Between Dopamine Antagonists and Increased Conversion to Exudative Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251330338},
pmid = {40191068},
issn = {2474-1272},
abstract = {Purpose: To investigate whether modulating dopamine signaling affects conversion to exudative age-related macular degeneration (AMD). Methods: A retrospective cohort study was performed using the Duke Epic database. Eyes from patients with a diagnosis of nonexudative AMD with at least 1 year of follow-up were evaluated for conversion to exudative AMD. Eyes with an AMD diagnosis were evaluated for age, sex, smoking history, hypertension, Age-Related Eye Disease Study (AREDS) or AREDS2 prescription, dopamine-modulating therapy prescription, and indication for dopamine-modulating therapy. Generalized estimating equations were used to calculate odds ratios for individual variables on conversion from nonexudative to exudative AMD. Results: Five hundred fifty-eight eyes of 354 patients with an initial diagnosis of nonexudative AMD were evaluated for conversion to exudative AMD. Conversion to exudative AMD was significantly higher in patients who had been on dopamine antagonist therapies for at least 3 years than in patients who were not on any dopamine-modulating therapies. After controlling for other variables, dopamine antagonists were associated with an increased risk for conversion to exudative AMD at 3 years of follow-up (P = .005). Conclusions: These findings suggest that antagonizing dopamine signaling may be associated with the development of macular neovascularization in eyes with nonexudative AMD. Although the data are observational, these findings warrant further investigation of dopamine signaling in conversion to exudative AMD.},
}
@article {pmid40191000,
year = {2025},
author = {Rush, RB and Klein, W and Reinauer, RM},
title = {Real-World Outcomes with Complement Inhibitors for Geographic Atrophy: A Comparative Study of Pegacetacoplan versus Avacincaptad Pegol.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1167-1174},
pmid = {40191000},
issn = {1177-5467},
abstract = {PURPOSE: To compare real-world outcomes in subjects who underwent treatment with intravitreal avacincaptad pegol (IVA) or intravitreal pegacetacoplan (IVP) for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>METHODS: This study was undertaken as a retrospective, comparative assessment of subjects who underwent IVA or IVP treatment for GA secondary to AMD at two community-based ophthalmology practices. All subjects included in the study had a visual acuity of &#x2265;20/200 at baseline, a total GA lesion area of &#x2265;1.5 mm[2] and &#x2264;17.5 mm[2]at baseline, and follow-up of 12-months following IVA or IVP initiation. The primary outcome was change in GA lesion size at 12 months. Secondary outcomes were change in logMAR vision at 12 months, total number of complement injections administered over 12 months, and the incidence of exudation at 12 months.<br><br>RESULTS: A total of 112 subjects were analyzed. There were no significant differences in baseline characteristics between treatment groups. There were no significant differences between IVA and IVP in change in total GA lesion size [1.19 (&#xb1;0.33) mm[2] versus 1.28 (&#xb1;0.37) mm[2]; p = 0.61], change in visual acuity [-0.1 (-0.04 to -0.16) logMAR versus -0.09 (-0.05 to -0.13) logMAR; p = 0.57], or exudation (p = 0.66) over the 12 month study period, respectively. However, the IVA cohort received more injections compared to the IVP group at 12 months (9.05 (&#xb1;1.06) versus 5.96 (&#xb1;2.01); p < 0.01).<br><br>CONCLUSION: This real-world study reports that treatment with IVA and IVP have similar visual and anatomic outcomes at 12-months, although subjects undergoing treatment with IVP may receive fewer injections to obtain these outcomes. Further studies comparing the safety and efficacy of IVA and IVP are warranted.},
}
@article {pmid40190424,
year = {2025},
author = {Hua, Z and Zhu, Q and Yang, J and Zheng, Y and Yang, W and Li, D and Cui, Y and Shen, L and Rao, L and Zhang, X and Yuan, L},
title = {Metformin inhibits subretinal fibrosis by activating Klotho by miR-126-5p.},
journal = {Cytotechnology},
volume = {77},
number = {3},
pages = {84},
pmid = {40190424},
issn = {0920-9069},
abstract = {Subretinal fibrosis is a main cause of visual loss in patients with neovascular age-related macular degeneration (nAMD), for whom there has been a lack of effective medication. Metformin can improve inflammation and angiogenesis in eye diseases. This study aimed to investigate the mechanism by which metformin inhibits subretinal fibrosis. A subretinal fibrosis cell model was induced by treating human retinal pigment epithelial cells (ARPE-19) with TGF-β1, a subretinal fibrosis mouse model was induced by a laser, and both cells and mice were treated with metformin. Cell proliferation, migration, and invasion were detected by CCK-8, scratch, and Transwell assays. Western blotting and immunofluorescence were used to evaluate protein expression levels, and RT‒qPCR was used to detect gene expression levels. HE and Masson staining were used to observe the morphological changes in retinal and choroidal tissues. Metformin treatment inhibited the TGF-β1-induced proliferation, migration, invasion and epithelial‒mesenchymal transition (EMT) of ARPE-19 cells and effectively ameliorated laser-induced subretinal fibrosis in mice. Mechanistically, metformin inhibits the expression of miR-126-5p, promotes Klotho synthesis, slows the progression of subretinal fibrosis, and miR-126-5p targets and negatively regulates Klotho. Metformin activates Klotho by inhibiting miR-126-5p, thereby reversing TGF-β1-induced ARPE-19 cell EMT and improving laser-induced subretinal fibrosis in mice.},
}
@article {pmid40190180,
year = {2025},
author = {Delmas, D and Perus, M and Aires, V and Hermetet, F},
title = {Current Advances in the Combination of Fatty Acids and Resveratrol to Fight Ocular Diseases.},
journal = {Molecular nutrition &amp; food research},
volume = {69},
number = {15},
pages = {e70037},
pmid = {40190180},
issn = {1613-4133},
mesh = {Humans ; Resveratrol ; *Macular Degeneration/drug therapy/prevention &amp; control ; Eicosapentaenoic Acid/therapeutic use/pharmacology ; *Fatty Acids, Omega-3/therapeutic use/pharmacology ; *Stilbenes/therapeutic use/pharmacology/administration &amp; dosage ; Docosahexaenoic Acids/therapeutic use/pharmacology ; Animals ; *Eye Diseases/drug therapy ; },
abstract = {Omega-3 polyunsaturated fatty acids (PUFA) and polyphenols have attracted interest to counteract ocular diseases and more specifically age-related macular degeneration (AMD). This eye disease, which is the leading cause of irreversible blindness in industrialized countries, is characterized by damage to the central part of the retina, the macula. Despite therapeutic advances with the use of anti-vascular endothelial growth factor (VEGF) monoclonal antibodies, numerous resistance mechanisms that worsen visual impairment have been identified. In this context, we highlight the exceptional potential of polyphenols and PUFA in addressing AMD through their actions on the different molecular mechanisms involved in AMD progression. More specifically, this review focuses on the current understanding of the effects of resveratrol, as well as docosahexaenoic and eicosapentaenoic acids, two prominent omega-3 PUFA, and the combination of these compounds. We also discuss the limitations and explore future directions for the combined use of these natural products as preventive or complementary therapies to preserve vision and slow disease progression.},
}
@article {pmid40189888,
year = {2025},
author = {Cao, HZ and Wang, Y},
title = {[Research progress on biomechanical characteristics of the posterior eye and vitreoretinal diseases and optic neuropathy].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {61},
number = {4},
pages = {298-303},
doi = {10.3760/cma.j.cn112142-20250201-00046},
pmid = {40189888},
issn = {0412-4081},
support = {2022YFC2404502//National Key Research and Development Program of China/ ; 82271118//General Program of the National Natural Science Foundation of China/ ; 21JCZDJC01190//Tianjin Science and Technology Planning Project/ ; TJWJ2022XK036//Tianjin Health Science and Technology Project/ ; TJYXZDXK-016A//Construction Project of Key Medical Disciplines (Special Project) in Tianjin/ ; },
mesh = {Humans ; Biomechanical Phenomena ; *Optic Nerve Diseases/physiopathology ; *Posterior Eye Segment ; Bruch Membrane ; *Retinal Diseases/physiopathology ; Optic Disk ; },
abstract = {The occurrence and development of biological tissue diseases are closely related to their biomechanical properties. In recent years, significant achievements have been made in the research on the biomechanical properties of the cornea and sclera, and the research on the association between the biomechanics of the posterior eye and eye diseases has also been continuously advanced. This review systematically collates the research on the biomechanical characteristics of the retina, Bruch's membrane-choroid complex (BMCC), and optic nerve head. The retina is anisotropic, with the elastic modulus increasing from the inner layer to the photosensitive layer. The internal limiting membrane has high mechanical strength and stiffness, and these properties change with age. The stiffness of the BMCC increases with strain, and its biomechanical changes are closely linked to aging and age-related diseases. The stress-strain pattern of the optic nerve head is affected by multiple factors and plays a crucial role in diseases such as glaucoma. These biomechanical properties are of great significance in the pathogenesis of diseases such as age-related macular degeneration, diabetic retinopathy, and glaucomatous optic neuropathy, and are also widely applied in the optimization of clinical surgeries, disease monitoring, and diagnosis. However, currently, the research on the biomechanics of the posterior segment of the eye is still in its infancy. The mechanical regulation mechanisms of multiple factors such as age, intraocular pressure, blood flow, and axial length have not been fully elucidated, and aspects such as matrix protein remodeling and post-translational modifications also require in-depth research.},
}
@article {pmid40188286,
year = {2025},
author = {Grosso, A and Borrelli, E and Sacchi, M and Calzetti, G and Ceruti, P and Neri, G and Marchetti, M and Pinna, A and Kostin, V and Reibaldi, M and Borsello, T and Vizzeri, G},
title = {Neuroprotection beyond intraocular pressure: game changer or quiet addiction.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {7},
pages = {1755-1763},
pmid = {40188286},
issn = {1435-702X},
mesh = {Humans ; *Neuroprotective Agents/therapeutic use ; *Intraocular Pressure/physiology/drug effects ; *Glaucoma/physiopathology/drug therapy ; *Neuroprotection/physiology ; *Macular Degeneration/physiopathology/drug therapy ; Oxidative Stress ; Retinal Ganglion Cells/pathology ; },
abstract = {The topic of neuroprotection in glaucoma and age-related macular degeneration (AMD) is well disseminated in the literature. However, the problem is providing ophthalmologists with clear, evidence-based messages to draw on. This review examines the landscape of neuroprotective therapies for glaucoma and AMD. While promising neuroprotective agents, such as citicoline and nicotinamide, have been explored for their potential to mitigate neurodegeneration in glaucoma, robust clinical evidence validating their efficacy remains limited and there is a need for further large-scale, long-term studies to substantiate the neuroprotective effects of these agents. Maintaining low intraocular pressure plays a vital role in preventing neuronal death in glaucoma. AMD has traditionally been considered a disease affecting the outer retinal layers; however, growing evidence suggests that the inner layers are also involved. Neuroprotection is an emerging area of research, with strategies focusing on alleviating oxidative stress, inflammation and apoptosis. A reassessment of clinical endpoints and methodologies in neuroprotection research is critical to better evaluate the efficacy of these therapies in glaucoma and AMD.},
}
@article {pmid40187761,
year = {2025},
author = {Gnanaraj, R and Lisker-Cervantes, A and Patnaik, J and Rajeswaren, V and Mehta, N and Gange, W and Lynch, AM and Palestine, A and Mathias, M and Manoharan, N and Mandava, N and Forest, TEC},
title = {Multimodal imaging biomarkers for progression from intermediate to advanced age-related macular degeneration (AMD): a 10-year prospective longitudinal cohort study from the University of Colorado AMD registry.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40187761},
issn = {2397-3269},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; UM1 TR004399/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; Disease Progression ; Male ; Prospective Studies ; Aged ; *Tomography, Optical Coherence/methods ; *Multimodal Imaging/methods ; *Registries ; Colorado/epidemiology ; Follow-Up Studies ; Biomarkers ; *Fluorescein Angiography/methods ; Aged, 80 and over ; Longitudinal Studies ; *Wet Macular Degeneration/diagnosis/diagnostic imaging ; Middle Aged ; *Geographic Atrophy/diagnosis ; Fundus Oculi ; },
abstract = {OBJECTIVE: To evaluate multimodal imaging (MMI) biomarkers for predicting progression from intermediate to advanced age-related macular degeneration (AMD).<br><br>METHODS AND ANALYSIS: This prospective longitudinal cohort study included patients with intermediate AMD (iAMD) enrolled in the University of Colorado AMD registry between July 2014 and August 2023, with follow-up through February 2024. At enrolment, patients' medical histories and MMI were collected. Baseline and follow-up imaging were reviewed for progression to geographic atrophy (GA) and neovascular AMD (nAMD). Univariate and multivariable Cox proportional hazard modelling with competing risks to determine HRs for progression.<br><br>RESULTS: A total of 367 patients (733 eyes) with iAMD were included in the study, with a median follow-up of 27.8 months. During this period, 100 eyes progressed to GA, 58 to nAMD. Adjusted for age, BMI and hypertension, progression to nAMD was significantly associated with soft drusen (HR 5.31, 95%&#x2009;CI 1.95 to 14.4, p=0.001), pigmentary changes (HR 2.74, 95%&#x2009;CI 1.52 to 4.92, p=0.0008) on colour fundus photography (CFP) and subretinal hyper-reflective material (SHRM) (HR 3.36, 95%&#x2009;CI 1.88 to 6.02, p<0.0001) and intraretinal hyper-reflective foci (IHRF) (HR 3.12, 95%&#x2009;CI 1.74 to 5.57, p=0.0001) on optical coherence tomography (OCT). Adjusted for age, progression to GA was predicted by soft drusen (HR 1.90, 95%&#x2009;CI 1.11 to 3.27, p=0.020), drusenoid pigment epithelial detachment (PED) (HR 5.51, 95%&#x2009;CI 2.49 to 12.2, p<0.0001), avascular non-drusenoid PED (HR 6.59, 95%&#x2009;CI 1.54 to 28.1, p=0.011), pigmentary changes (HR 4.44, 95%&#x2009;CI 2.84 to 6.96, p<0.0001) on CFP and nnSRF (HR 6.41, 95%&#x2009;CI 1.39 to 29.6, p=0.017), SHRM (HR 2.55, 95%&#x2009;CI 1.45 to 4.49, p=0.001), drusenoid PED (HR 2.25, 95%&#x2009;CI 1.43 to 3.55, p=0.0005), avascular non-drusenoid PED (HR 4.67, 95%&#x2009;CI 2.45 to 8.92, p<0.0001), IHRF (HR 6.27, 95%&#x2009;CI 3.89 to 10.1, p<0.0001) and incomplete retinal pigment epithelium and outer retinal atrophy (HR 9.42, 95%&#x2009;CI 5.82 to 15.2, p<0.0001) on OCT (table 3).<br><br>CONCLUSIONS: Key imaging biomarkers associated with the progression were identified, which may offer prognostic information for providers. However, the study is limited by its predominantly Caucasian population and single-centre design, which may affect the generalisability of certain biomarkers.},
}
@article {pmid40185386,
year = {2025},
author = {Lei, S and Liu, Y},
title = {Identifying blood mitochondrial DNA copy number as a biomarker for development of neurodegenerative diseases: Evidence from Mendelian randomization analysis.},
journal = {Neuroscience},
volume = {573},
number = {},
pages = {421-429},
doi = {10.1016/j.neuroscience.2025.04.003},
pmid = {40185386},
issn = {1873-7544},
mesh = {Humans ; *DNA, Mitochondrial/blood/genetics ; Mendelian Randomization Analysis ; *Neurodegenerative Diseases/genetics/blood ; *DNA Copy Number Variations/genetics ; Genome-Wide Association Study ; Biomarkers/blood ; },
abstract = {Mitochondrial dysfunction has been associated with neurodegenerative diseases (NDDs). This study aimed to explore the association between blood mitochondrial DNA copy number (mtDNA-CN) and development of NDDs. This study was based on two-sample Mendelian randomization (MR) analysis. The genome wide association study (GWAS) data of NDDs including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD), multiple sclerosis (MS), Parkinson's disease (PD), primary open-angle glaucoma (POAG), and vascular dementia (VD) was obtained from FinnGen consortium. Inverse-variance weighted (IVW) was applied as the primary approach for MR estimation. MR results revealed that blood mtDNA-CN exhibited a significant relationship with the incidence of AD (IVW-P = 0.011, odds ratio [OR] = 0.65) and AMD (IVW-P = 0.038, OR = 0.64). However, there was no significant association observed between blood mtDNA-CN and other NDDs (IVW-P > 0.05). Our findings supported the relationship between mitochondrial dysfunction and development of AD and AMD, and that blood mtDNA-CN may serve as a potential biomarker for the incidence of these two NDDs.},
}
@article {pmid40184546,
year = {2025},
author = {Sisk, RA},
title = {Occlusive Retinal Vasculitis After Aflibercept 8mg Injection for Wet Macular Degeneration.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001757},
pmid = {40184546},
issn = {1937-1578},
abstract = {PURPOSE: To describe a case of occlusive retinal vasculitis (ORV) following intravitreal aflibercept 8mg injection for wet macular degeneration.<br><br>METHODS: Retrospective, interventional case report.<br><br>RESULTS: A 72-year-old female presented with classic ORV 11 days after intravitreal aflibercept 8mg injection in her left eye for wet macular degeneration. Visual acuity (VA) declined from 20/30 to 20/400. Laboratory investigations including Gram stain and cultures of vitreous aspirate, studies for infectious and non-infectious uveitis and hypercoagulable state were all negative. Oral prednisone, sub-Tenon's triamcinolone acetonide (STTA), intravitreal dexamethasone and antibiotic injections, and topical steroids resulted in visual and anatomic improvement. ORV recurred when prednisone was tapered to 10mg/day and was controlled with additional STTA, oral solumedrol, and a 0.18mg fluocinolone acetonide implant. Subsequently exudation from wet macular degeneration recurred and responded to intravitreal faricimab with recovery to 20/30.<br><br>CONCLUSIONS: ORV is a rare complication of some intravitreal anti-VEGF medications and infectious causes of endophthalmitis. It can be managed with aggressive steroid treatment for an excellent visual outcome in some cases, although the disease may be chronic or recurrent.},
}
@article {pmid40183986,
year = {2025},
author = {Bottazzi, L and Barlocci, E and Sacconi, R and Battista, M and Servillo, A and Beretta, F and Bandello, F and Querques, G},
title = {Choroidal neovascularization secondary to punctate inner choroidopathy vs myopia: clinical outcomes after 1-year of treatment.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {7},
pages = {1859-1865},
pmid = {40183986},
issn = {1435-702X},
mesh = {Humans ; *Choroidal Neovascularization/etiology/drug therapy/diagnosis ; Retrospective Studies ; Female ; Male ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Middle Aged ; *Choroid/pathology ; Fundus Oculi ; *Myopia/complications/diagnosis ; Case-Control Studies ; Treatment Outcome ; *Ranibizumab/administration &amp; dosage ; Time Factors ; *White Dot Syndromes/complications/diagnosis/drug therapy ; Adult ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Bevacizumab/administration &amp; dosage ; Aged ; },
abstract = {BACKGROUND: One of the most important complications of punctate inner choroidopathy (PIC) is the development of an inflammatory type 2 choroidal neovascularization (iCNV); however, also myopic macular degeneration due to high myopia could be complicated by a type- 2 CNV (mCNV). The aim of this work is to assess similarities and differences in the response to anti-VEGF treatment between mCNV and iCNV during a one-year follow-up, number of intravitreal injections required to control the CNV and the number of recurrences that occurred during a one-year follow-up were evaluated.<br><br>METHODS: Retrospective, longitudinal, case-control study. Patients diagnosed with myopic iCNV secondary to PIC or to simple myopia referring to San Raffaele Hospital were enrolled from January 2021 to December 2022. Choroidal thickness (ChT) and best-corrected visual acuity (BCVA) were measured at the onset of CNV, after resolution of exudation after treatment, and at 1-year follow-up. Primary outcomes included the analysis of the number of intravitreal injections needed and the incidence of recurrences. Secondary outcomes comprised the analysis of ChT.<br><br>RESULTS: Thirty-seven eyes (37 patients) were enrolled. Sixteen eyes were affected by myopic iCNV secondary to PIC, and 21 eyes by simple mCNV. BCVA significantly improved in both myopic iCNV group (from 0.27 &#xb1;&#x2009;0.12 at the baseline to 0.11 &#xb1;&#x2009;0.08 LogMAR at 12 months follow-up, p&#x2009;< 0.001) and simple mCNV group (from 0.37 &#xb1;&#x2009;0.22 at the baseline to 0.23 &#xb1;&#x2009;0.17 LogMAR at 12 months follow-up, p&#x2009;< 0.001). A significant difference in ChT was found comparing myopic iCNV and simple mCNV groups (mean sub-CNV ChT of 258 &#xb1;&#x2009;116 &#x3bc;m and 89 &#xb1;&#x2009;14 &#x3bc;m, respectively, p&#x2009;< 0.001). Sub-CNV ChT significantly decreases during the follow-up in the PIC group (from 258 &#xb1;&#x2009;116 &#x3bc;m to 192 &#xb1;&#x2009;118 &#x3bc;m, p&#x2009;= 0.002), whereas no differences were disclosed in the myopic group. CNV secondary to PIC needed more anti-VEGF intravitreal injections to achieve resolution of exudation (3.2 &#xb1;&#x2009;1.2 vs 2.1 &#xb1;&#x2009;1.1 intravitreal injections, p&#x2009;= 0.003) and they were characterized by higher number of relapses (44% vs 20%, p&#x2009;< 0.001) in comparison to simple myopic group.<br><br>CONCLUSIONS: PIC group showed a more aggressive pattern of CNV, characterized by higher number of relapses and intravitreal injections needed. Moreover, a higher ChT below the lesion was detected in PIC group in comparison to simple myopic group.},
}
@article {pmid40183456,
year = {2025},
author = {Kong, M and Li, J and Tong, N},
title = {The role of peripheral blood microRNAs in the pathogenesis and treatment response of age-related macular degeneration.},
journal = {Future science OA},
volume = {11},
number = {1},
pages = {2482499},
pmid = {40183456},
issn = {2056-5623},
abstract = {Age-related macular degeneration is a leading cause of vision loss in aging populations, driven by complex interactions between genetic, environmental, and molecular factors. MicroRNAs have emerged as crucial regulators of cellular processes such as oxidative stress, inflammation, and angiogenesis, all of which contribute to AMD pathogenesis. This narrative review aims to summarize the involvement of peripheral blood microRNAs in the pathogenesis of AMD, focusing on key pathways such as oxidative stress, inflammation, and angiogenesis. Additionally, it explores their potential as biomarkers for predicting treatment response, particularly to anti-VEGF therapies. The potential of miRNAs as noninvasive biomarkers for early diagnosis and personalized treatment strategies is also explored, highlighting future directions for research.},
}
@article {pmid40183100,
year = {2025},
author = {Wang, X and Liang, X and Huang, S and Wei, M and Xu, Y and Chen, X and Miao, Y and Zong, R and Lin, X and Li, S and Liu, Z and Chen, Q},
title = {Metformin inhibits pathological retinal neovascularization but promotes retinal fibrosis in experimental neovascular age-related macular degeneration.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1547492},
pmid = {40183100},
issn = {1663-9812},
abstract = {PURPOSE: This study aims to investigate the effects and mechanism of action of metformin on retinal neovascularization and fibrosis in a mouse model of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Very low-density lipoprotein receptor knockout (Vldlr [-/-]) mice, a mouse model of nAMD, were used in this study. Vldlr [-/-] mice were administered metformin on postnatal day (P) 20 for 20&#xa0;days (early stage of pathological change) or at 5.5&#xa0;months of age for 45&#xa0;days (late stage of pathological change). Retinal leakage was examined by fundus fluorescein angiography (FFA). Retinal neovascularization was assessed by lectin staining. Retinal fibrosis was assessed by Western blotting, immunofluorescence staining, and Masson's trichrome staining.<br><br>RESULTS: Retinal vascular leakage and neovascularization were significantly reduced in Vldlr [-/-] mice treated with metformin compared to those treated with the vehicle at P40. The protein levels of inflammatory factors and phospho(p)-STAT3 were decreased, and P38 and ERK signaling were suppressed in the retinas of metformin-treated Vldlr [-/-] mice relative to those in the control group at P40. Fibrotic markers were upregulated in the retinas of Vldlr [-/-] mice treated with metformin compared to those treated with the vehicle at 7&#xa0;months. Levels of the inflammatory factors and p-STAT3 were increased, and PI3K/AKT, P38, and ERK signaling were upregulated in the retinas of metformin-treated Vldlr [-/-] mice compared to those in the control group at 7&#xa0;months.<br><br>CONCLUSION: Metformin inhibits pathological retinal neovascularization but promotes fibrosis in experimental nAMD. These results provide evidence and highlight important considerations for the clinical use of metformin in different stages of nAMD.},
}
@article {pmid40183099,
year = {2025},
author = {Xiong, M and Peng, J and Zhou, S and Gao, Q and Lu, J and Ou, C and Song, H and Peng, Q},
title = {Lycium barbarum L.: a potential botanical drug for preventing and treating retinal cell apoptosis.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1571554},
pmid = {40183099},
issn = {1663-9812},
abstract = {Retinal cell apoptosis is the primary pathological process in many retinal diseases, including retinitis pigmentosa and age-related macular degeneration, which can cause severe visual impairment and blindness. Lycium barbarum L., a traditional Chinese medicinal botanical drug, has a long history and extensive application in ophthalmic disease prevention and treatment. This study systematically reviewed the key active metabolites in L. barbarum L., including L. barbarum polysaccharides, carotenoids, and flavonoids, that exert retinal protective effects. A comprehensive analysis of the pharmacological effects and underlying molecular mechanisms of L. barbarum L. and its active metabolites in the prevention and treatment of retinal cell apoptosis, including essential aspects such as antioxidant activity, anti-inflammatory properties, autophagy regulation, and mitochondrial function preservation, is essential to establish a comprehensive and solid theoretical basis for further investigation of the medicinal value of L. barbarum L. in ophthalmology and provide a reference for future research directions.},
}
@article {pmid40180316,
year = {2025},
author = {Fein, JG and Vakharia, PS and Chous, AP and Desai, R and Silva, FQ and Reed, K and Berliner, AJ and Vitti, R and Wykoff, CC},
title = {Clinical Outcomes in Neovascular Age-related Macular Degeneration with Aflibercept 8 mg in the Phase II CANDELA Study.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {9},
pages = {915-918},
doi = {10.1016/j.oret.2025.03.023},
pmid = {40180316},
issn = {2468-6530},
}
@article {pmid40179629,
year = {2025},
author = {Liu, X and Zhang, J and Zhang, Y and Chen, L and Luo, L and Tang, J},
title = {Weakly supervised segmentation of retinal layers on OCT images with AMD using uncertainty prototype and boundary regression.},
journal = {Medical image analysis},
volume = {102},
number = {},
pages = {103572},
doi = {10.1016/j.media.2025.103572},
pmid = {40179629},
issn = {1361-8423},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; Algorithms ; *Retina/diagnostic imaging ; Uncertainty ; },
abstract = {Retinal layer segmentation for optical coherence tomography (OCT) images of eyes is a critical step in the diagnosis and treatment of age-related macular degeneration (AMD) eye disease. In recent years, dense annotation supervised OCT layer segmentation methods have made significant progress. However, obtaining pixel-by-pixel labeled masks from OCT retinal images is time-consuming and labor-intensive. To reduce dependence on dense annotations, this paper proposes a novel weakly supervised layer segmentation method with Uncertainty Prototype module and Boundary Regression loss (W-UPBR), which only requires scribble annotations. Specifically, we first propose a feature enhancement U-Net (FEU-Net) to alleviate the severe layer distortion problem in OCT images with AMD. And this model serves as the backbone of a dual-branch network framework to enhance features. Within FEU-Net, in addition to the basic U-Net, two modules have been proposed: the global-local context-aware (GLCA) module, which captures both global and local contextual information, and the multi-scale fusion (MSF) module, designed for fusing multi-scale features. Secondly, we propose an uncertainty prototype module that combines the uncertainty-guided prototype and distance optimization loss. This module aims to exploit the similarities and dissimilarities between OCT images, thereby reducing mis-segmentation in layers caused by interference factors. Furthermore, a mixed pseudo-label strategy is incorporated to mix different predictions to alleviate the limitations posed by insufficient supervision and further promote network training. Finally, we design a boundary regression loss that constrains the boundaries in both 1D and 2D dimensions to enhance boundary under the supervision of generated mixed pseudo-labels, thereby reducing topological errors. The proposed method was evaluated on three datasets, and the results show that the proposed method outperformed other state-of-the-art weakly supervised methods and could achieve comparable performance to fully supervised methods.},
}
@article {pmid40178482,
year = {2025},
author = {},
title = {Erratum in: Porcine Sub-Retinal Pigment Epithelium Deposits: A Model for Dry Age-Related Macular Degeneration With Comparison to Human Drusen.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {10},
doi = {10.1167/iovs.66.4.10},
pmid = {40178482},
issn = {1552-5783},
}
@article {pmid40177921,
year = {2025},
author = {Chambers, JD and Beinfeld, MT and Richardson, T and Pangrace, M},
title = {Assessing variation in US payer coverage of anti-vascular endothelial growth factor therapies for the treatment of age-related macular degeneration, diabetic retinopathy, and diabetic macular edema.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {31},
number = {5},
pages = {451-460},
pmid = {40177921},
issn = {2376-1032},
mesh = {Humans ; *Diabetic Retinopathy/drug therapy/economics ; United States ; *Macular Edema/drug therapy/economics ; *Macular Degeneration/drug therapy/economics ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/economics/therapeutic use ; *Insurance Coverage/economics/statistics &amp; numerical data ; Medicare Part C/economics ; },
abstract = {BACKGROUND: Timely anti-vascular endothelial growth factor (anti-VEGF) therapy is recommended to preserve vision in age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME). Coverage of anti-VEGF agents for the treatment of retinal diseases varies, resulting in administrative burdens for providers and treatment delays for patients.<br><br>OBJECTIVE: To examine how US commercial and Medicare Advantage (MA) health plans cover anti-VEGF therapies for the treatment of retinal diseases using information from the Tufts Medical Center Specialty Drug Evidence and Coverage Database.<br><br>METHODS: This descriptive study evaluated coverage of US Food and Drug Administration (FDA)-approved anti-VEGF drugs for AMD, DR, and DME current as of April 2024 using the Specialty Drug Evidence and Coverage Database from 18 of the largest US commercial health plans and MA offerings from a subset of 6 of these plans.<br><br>RESULTS: Substantial variation exists in commercial coverage across FDA-approved anti-VEGF therapies for AMD, DR, and DME. Descriptive assessment showed that approximately 65% of commercial coverage decisions and approximately 52% of MA decisions included restrictions beyond the FDA label. Coverage decisions for originator products were more likely to include restrictions compared with those for biosimilar products. Step therapy protocols were found in up to 75% of plans but were variable by drug, with most requiring a first-line trial of bevacizumab. Evidence cited to support coverage restrictions was likewise variable.<br><br>CONCLUSIONS: Descriptive data show that US commercial and MA coverage and step therapy protocols vary substantially across health plans, which may potentially contribute to administrative burdens and treatment delays.},
}
@article {pmid40174929,
year = {2025},
author = {Guymer, RH and Hunyor, AP and Chen, FK and Lim, LL and Arnold, J and Abbott, CJ},
title = {Readiness of optometrists in the management of geographic atrophy: a survey of optometrists in Australia.},
journal = {Clinical &amp; experimental optometry},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/08164622.2025.2458171},
pmid = {40174929},
issn = {1444-0938},
abstract = {CLINICAL RELEVANCE: Geographic atrophy is a leading cause of severe vision loss and is estimated to affect around 100,000 people in Australia alone. This survey is topical for clinical optometrists as the first treatment for geographic atrophy has just been approved by the Australian Therapeutics Goods Administration and may soon become available in Australia.<br><br>BACKGROUND: Considering that treatments for geographic atrophy secondary to age-related macular degeneration are likely imminent, a survey of Australian optometrists was conducted to gauge their readiness in caring for people with geographic atrophy.<br><br>METHODS: The Royal Australian and New Zealand College of Ophthalmologists age-related macular degeneration referral guidelines working group determined 26 survey questions relating to management of geographic atrophy. Strength of agreement questions utilised a 5-point Likert scale. Optometrists answered anonymously during January to March 2024.<br><br>RESULTS: There were 101 survey responses. Almost all (97%) respondents have access to colour fundus photography, three-quarters (74%) to optical coherence tomography, and almost half (44%) to fundus autofluorescence. Almost all (97%) see patients with GA regularly, with 73% seeing at least two geographic atrophy patients per month and the majority reviewing them every 6 months. Around half were confident in differentiating geographic atrophy from inherited retinal disease (49%) and confident in identifying early signs of atrophy (44%). Around half (46%) nominated that they would refer over 50% of their current geographic atrophy patients to ophthalmology for assessment of their suitability for new treatments. Eighty-three percent would refer a patient with good vision (6/12 or better) to initiate treatment to save encroachment on the fovea. Respondents were keen to receive more education about diagnosis (88%) and new treatments (93%).<br><br>CONCLUSION: Optometrists are preparing for changes in the clinical management of geographic atrophy and are keen to receive further education to ensure optimal patient-centric care as new treatments become available.},
}
@article {pmid40173349,
year = {2025},
author = {Azuma, K and Santo, D and Sugiyama, S and Aoki, N and Aoki, S and Kitamoto, K and Terao, R and Inoue, T and Obata, R},
title = {Polarization-sensitive optical coherence tomography features of the repair tissue following retinal pigment epithelium tear and functional correlation with visual outcomes.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001752},
pmid = {40173349},
issn = {1937-1578},
abstract = {PURPOSE: To investigate changes in melanin distribution and retinal sensitivity following a retinal pigment epithelium (RPE) tear in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Five cases of nAMD with RPE tears involving the fovea within 1 month of onset were examined. Using polarization-sensitive optical coherence tomography, entropy-a quantitative indicator of melanin distribution-was measured at baseline and 6 months at the level of Bruch's membrane. Retinal sensitivity was assessed with a microperimeter, and entropy was averaged across 25 grids within a 6-degree radius. The relationship between changes in entropy and retinal sensitivity was analyzed.<br><br>RESULTS: Entropy significantly increased in the tear area (from 0.19 to 0.22, p=0.026), whereas it decreased in the non-tear area. Retinal sensitivity also significantly increased in the tear area (from 12.7 to 16.3 dB, p=0.002). Although entropy and retinal sensitivity were not directly correlated in each area, their changes were significantly correlated, regardless of area type. Changes in central grid entropy were associated with changes in logarithm of the minimum angle of resolution visual acuity.<br><br>CONCLUSION: Six months post RPE tear, entropy and retinal sensitivity increased in tear areas; entropy changes were linked to retinal sensitivity and visual acuity, indicating functional adjustments following the tear.},
}
@article {pmid40171949,
year = {2025},
author = {Macečková Brymová, A and Rodriguez-Jimenez, FJ and Konrad, A and Nemesh, Y and Thottappali, MA and Artero-Castro, A and Nyshchuk, R and Kolesnikova, A and Müller, B and Studenovska, H and Juhasova, J and Juhas, S and Valekova, I and Lukovic, D and Aleman, C and Ardan, T and Drutovič, S and Motlik, J and Ellederova, Z and Straňák, Z and Veith, M and Lytvynchuk, L and Sharma, R and Bharti, K and Petrovski, G and Jendelova, P and Stieger, K and Erceg, S},
title = {Delivery of Human iPSC-Derived RPE Cells in Healthy Minipig Retina Results in Interaction Between Photoreceptors and Transplanted Cells.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {20},
pages = {e2412301},
pmid = {40171949},
issn = {2198-3844},
support = {TO01000107//Norway Grants and Technology Agency of the Czech Republic/ ; CZ.02.01.01/00/22_008/0004562//European Regional Development Fund by Programme Johannes Amos Comenius/ ; 21180//Foundation AFM-Telethon/ ; 202010-10//Fundaci&#xf3; la Marat&#xf3; de TV3/ ; //Instituto de Salud Carlos III (ISCIII) grant PI20/01119 co-funded by European Regional Development Fund (FEDER)/ ; //Univeridad Cardenal Herrera-CEU, CEU Universities GIR23/04/ ; },
mesh = {Animals ; Swine ; *Induced Pluripotent Stem Cells/cytology/transplantation ; *Retinal Pigment Epithelium/cytology/transplantation ; Swine, Miniature ; Humans ; *Retina/cytology ; *Photoreceptor Cells ; Macular Degeneration/therapy ; },
abstract = {In late stages of inherited and acquired retinal diseases such as Stargardt disease (STGD) or dry age-related macular degeneration (AMD), loss of retinal pigment epithelia (RPE) cells and subsequently photoreceptors in the macular area result in a dramatic decline of central visual function. Repopulating this area with functional RPE cells may prevent or decline the progression of photoreceptor loss. In the present study, the viability, survival, and integration of human induced pluripotent stem cell (hiPSC)-derived RPE cells (hiPSC-RPE) is assessed generated using clinical-grade protocol and cultured on a clinically relevant scaffold (poly-L-lactide-co-D, L-lactide, PDLLA) after subretinal implantation in immunosuppressed minipigs for up to 6 weeks. It is shown that transplanted hiPSC-RPE cells maintain the RPE cell features such as cell polarity, hexagonal shape, and cell-cell contacts, and interact closely with photoreceptor outer segments without signs of gliosis or neuroinflammation throughout the entire period of examination. In addition, an efficient immunosuppressing strategy with a continuous supply of tacrolimus is applied. Continuous verification and improvement of existing protocols are crucial for its translation to the clinic. The results support the use of hiPSC-RPE on PDLLA scaffold as a cell replacement therapeutic approach for RPE degenerative diseases.},
}
@article {pmid40170980,
year = {2025},
author = {Chakraborty, D and Sinha, TK and Sinha, S and Biswas, RK and Maiti, A and Boral, S and Das, A and Mandal, S and Bhattacharya, R and Dan, S and Rungta, D},
title = {CompaRative Safety Analysis of Innovator and BioSimilar Ranibizumab in Chorioretinal Vascular Diseases - The CRsIBS Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {1093-1102},
pmid = {40170980},
issn = {1177-5467},
abstract = {PURPOSE: To compare the safety profiles of biosimilar ranibizumab (Razumab™) and innovator ranibizumab (Accentrix™) in the management of chorioretinal vascular diseases across a large, diverse patient cohort in a multicenter retrospective study.<br><br>METHODS: This multicenter, retrospective study analyzed data from 39,226 eyes treated with either biosimilar or innovator ranibizumab across 21 centers in India between January 2016 and March 2024. Eligible patients received intravitreal injections for conditions including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (CNVM). Patients were followed for a minimum of three months, with adverse events documented during follow-up visits. Safety outcomes were assessed based on ocular and systemic adverse events, with statistical analyses comparing frequencies between groups using chi-square and t-tests.<br><br>RESULTS: A total of 46,520 injections were administered in the innovator group (20,283 eyes; mean 2.29&#xb1;1.53 injections per eye) and 45,310 injections in the biosimilar group (18,943 eyes; mean 2.39&#xb1;1.61 injections per eye). Both groups showed comparable safety profiles. Ocular adverse events were mostly mild, with similar rates of transient blurring, subconjunctival hemorrhage, and ocular pain. Serious ocular events, including endophthalmitis, were rare (2 cases in each group). Systemic adverse events, such as myocardial infarction and cerebrovascular accidents, were also rare, with no statistically significant differences between groups. A higher incidence of anterior chamber inflammation was noted in the biosimilar group (p=0.005), while headache was significantly more common in this group (p=0.0002).<br><br>CONCLUSION: This large-scale real-world study demonstrates that biosimilar ranibizumab offers a comparable safety profile to innovator ranibizumab in the management of chorioretinal vascular diseases. The affordability of biosimilar ranibizumab enhances its potential as a cost-effective alternative, particularly in resource-limited settings, without compromising safety.},
}
@article {pmid40170431,
year = {2025},
author = {de Faria Corrêa Roncato, D and Tombolini, B and de Faria Corrêa Roncato, L and Japiassú, R and Spessato, N and Sacconi, R and Querques, G and Bandello, F},
title = {A Brazilian case of extensive macular atrophy with pseudodrusen and non-exudative quiescent macular neovascularization.},
journal = {European journal of ophthalmology},
volume = {35},
number = {4},
pages = {NP44-NP48},
doi = {10.1177/11206721251333274},
pmid = {40170431},
issn = {1724-6016},
mesh = {Humans ; Male ; Aged ; Tomography, Optical Coherence ; Fluorescein Angiography ; *Retinal Neovascularization/diagnosis/complications ; *Retinal Drusen/diagnosis/complications ; *Geographic Atrophy/diagnosis/complications ; Visual Acuity ; Brazil ; *Macula Lutea/pathology ; },
abstract = {PurposeTo report a case of extensive macular atrophy with pseudodrusen (EMAP) complicated by a non-exudative quiescent type 1 macular neovascularization (MNV).Case descriptionA 65-years-old male patient complained of bilateral progressive visual loss and nyctalopia over the last ten years. Fundus examination showed in both eyes central foveal sparing geographic atrophy partially extending outside vascular arcades, reticular pseudodrusen (RPD), and mid-periphery pavingstone degenerations. On optical coherence tomography (OCT), RPD, basal laminar deposits, retinal pigmented epithelium and outer retinal atrophy were detected bilaterally. In left eye (LE), a perifoveal mid-reflective pigment epithelium detachment (PED) with no neovascular activity signs (e.g., macular hemorrhage, intraretinal/subretinal fluid, subretinal hyperreflective material) was found. Fluorescein angiography revealed in LE a hyperfluorescence coincident with PED without leakage on late phase. OCT-angiography displayed a pathological neovascular network consistent with a non-exudative type 1 neovascularization. No treatment was performed and the patient was closely followed. On last consultation six months later, MNV was stable with no identifiable activation signs. Based on these findings, a diagnosis of EMAP complicated by non-exudative quiescent type 1 neovascularization was hypothesized.DiscussionSimilarly to age-related macular degeneration, EMAP could be associated to non-exudative neovascularization. Choriocapillaris loss could be the trigger for the development of vascular sprouts, representing the precursor of non-exudative type 1 MNV.ConclusionThis case-report supported the importance of at least six-months follow-up for NE-MNV in EMAP. Further studies are needed to confirm our result and to consolidate therapeutic management of MNV in this rare macular disorder.},
}
@article {pmid40170390,
year = {2025},
author = {Mavridou, EP and Sergentanis, TN and Kapetanios, I and Theodossiadis, P and Chatziralli, I},
title = {Intravitreal Anti-Vascular Endothelial Growth Factor Agents in Patients with Neovascular Age-Related Macular Degeneration and Retinal Pigment Epithelial Tear: A Systematic Review and Meta-Analysis.},
journal = {Seminars in ophthalmology},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/08820538.2025.2486328},
pmid = {40170390},
issn = {1744-5205},
abstract = {PURPOSE: The purpose of this systematic review and meta-analysis is to evaluate the outcomes of continuing versus discontinuing intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment at various follow-up time-points in neovascular age-related macular degeneration (nAMD) patients who developed retinal pigment epithelium (RPE) tears following anti-VEGF therapy.<br><br>METHODS: Relevant publications were identified through a systematic search in the PubMed and EMBASE databases. The standardized mean differences (SMD), with their 95% confidence intervals (95% CI), were estimated using random effects models (DerSimonian-Laird), as appropriate. Meta-regression analysis was also performed.<br><br>RESULTS: Thirty studies (including 479 eyes with RPE tear) were eligible for the systematic review and meta-analysis. These studies examined the outcomes in patients who continued anti-VEGF treatment post-tear and those who discontinued it, with comparisons made separately for different timepoints in each group. In patients who continued anti-VEGF treatment, the pooled best-corrected visual acuity (BCVA) showed no statistically significant difference compared to baseline at any time-point of the follow-up. The pooled central subfield thickness (CST) improved at 12&#x2009;months, but did not reach a significant level (SMD -0.45; 95% CI: -0.99, 0.10, I[2]&#x2009;=&#x2009;49.5%, p&#x2009;=&#x2009;.159). Long-term follow-up indicated a decrease in the presence of subretinal and intraretinal fluid. In patients who discontinued intravitreal anti-VEGF treatment, there was a non-significant improvement in BCVA within the first 3&#x2009;months; however, BCVA fluctuated or worsened over time, and fibrosis development was observed.<br><br>CONCLUSIONS: This systematic review and meta-analysis found that intravitreal injections of anti-VEGF do not significantly impact visual acuity in patients with RPE tears at various follow-up timepoints, but may provide anatomical improvement.},
}
@article {pmid40170180,
year = {2025},
author = {Brunet, AA and James, RE and Swanson, P and Carvalho, LS},
title = {A review of the 661W cell line as a tool to facilitate treatment development for retinal diseases.},
journal = {Cell &amp; bioscience},
volume = {15},
number = {1},
pages = {41},
pmid = {40170180},
issn = {2045-3701},
abstract = {Retinal diseases encompass a diverse group of disorders that affect the structure and function of the retina, leading to visual impairment and, in some cases, irreversible vision loss. The investigation of retinal diseases is crucial for understanding their underlying mechanisms, identifying potential therapeutic targets, and developing effective treatments. The use of in vitro cell models has become instrumental in advancing our knowledge of these disorders, but given that these conditions usually affect retinal neuronal cell types, access to appropriate cell models can be potentially challenging. Among the available in vitro cell models, the 661W cone-like cell line has emerged as a valuable tool for studying various retinal diseases, ranging from monogenic conditions, such as inherited retinal diseases, to complex conditions such as age-related macular degeneration (AMD), diabetic retinopathy, amongst others. Developed from immortalized murine photoreceptor cells, and freely available for academics from its creator, the 661W cell line has offered visual scientists and clinicians around the world a reliable and well-characterised platform for investigating disease pathogenesis, exploring disease-specific molecular signatures, and evaluating potential therapeutic interventions. This review aims to provide an overview of the 661W cell line and its applications in the study of both inherited and acquired retinal diseases. By examining the applications and limitations of this unique cell line, we may gain valuable insights into its contributions in unravelling the complexities of retinal diseases and its potential impact on the development of novel treatments for these diseases.},
}
@article {pmid40169885,
year = {2025},
author = {Sarao, V and Veritti, D and Bonini, F and Martin, AA and Lanzetta, P},
title = {Early intraocular pressure dynamics following aflibercept 8 mg versus aflibercept 2 mg: a propensity score-matched analysis.},
journal = {Eye (London, England)},
volume = {39},
number = {10},
pages = {1933-1939},
pmid = {40169885},
issn = {1476-5454},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Intraocular Pressure/drug effects/physiology ; Male ; Female ; Intravitreal Injections ; Aged ; Prospective Studies ; *Angiogenesis Inhibitors/administration &amp; dosage ; Tonometry, Ocular ; Propensity Score ; *Macular Edema/drug therapy/physiopathology ; Diabetic Retinopathy/drug therapy/physiopathology ; Middle Aged ; *Wet Macular Degeneration/drug therapy/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Visual Acuity ; },
abstract = {PURPOSE: To compare early intraocular pressure (IOP) dynamics following intravitreal injections of aflibercept 8 mg versus aflibercept 2 mg using propensity score-matched analysis with fellow eye controls.<br><br>METHODS: This prospective observational study included treatment-na&#xef;ve patients with neovascular age-related macular degeneration (AMD) or diabetic macular oedema (DMO). Patients received aflibercept 8&#x2009;mg or 2&#x2009;mg based on investigator discretion. IOP was measured using iCare rebound tonometry at baseline (T0), 1&#x2009;min (T1), 10&#x2009;min (T2), 30&#x2009;min (T3), and 3 months (T4) after the initial treatment. Untreated fellow eyes served as controls. Secondary analyses evaluated predictors of significant IOP elevation.<br><br>RESULTS: A total of 1820 IOP measurements from 140 eyes (35 treated with aflibercept 8&#x2009;mg and 35 with aflibercept 2&#x2009;mg and their respective untreated fellow eyes) were analysed. Both formulations induced significant immediate IOP elevations at T1 (55.6&#x2009;&#xb1;&#x2009;15.2&#x2009;mmHg for 8&#x2009;mg, 54.2&#x2009;&#xb1;&#x2009;20.4&#x2009;mmHg for 2&#x2009;mg) compared to baseline values (p&#x2009;<&#x2009;0.001). Pressures decreased progressively, approaching baseline by T3 (19.3&#x2009;&#xb1;&#x2009;5.9&#x2009;mmHg for 8&#x2009;mg, 20.5&#x2009;&#xb1;&#x2009;6.6&#x2009;mmHg for 2&#x2009;mg), with no significant differences between doses (p&#x2009;>&#x2009;0.05). Pre-existing glaucoma emerged as the strongest predictor of sustained IOP elevation, while DMO eyes exhibited higher initial spikes compared to neovascular AMD. Three-month IOP remained stable across both groups.<br><br>CONCLUSIONS: Intravitreal administration of aflibercept 8&#x2009;mg demonstrates IOP dynamics comparable to the 2&#x2009;mg formulation, with rapid normalization of pressure spikes by 30&#x2009;min. These findings suggest enhanced monitoring may be beneficial for patients with glaucoma or DMO.},
}
@article {pmid40168152,
year = {2025},
author = {Giallongo, S and Bellia, F and Russo, A and Fallico, M and Polosa, R and Castellino, N and Longo, A and Emma, R and Partsinevelos, K and Caruso, M and Kartasasmita, AS and Sferrazzo, G and Barbagallo, IA and Caltabiano, R and Broggi, G and Alanazi, AM and Li Volti, G},
title = {Comparative Evaluation of Cigarette Smoke and a Heated Tobacco Product on Corneal Oxidative Stress in an Air/Liquid Interface Model.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {4},
pages = {4},
pmid = {40168152},
issn = {1552-5783},
mesh = {*Oxidative Stress/drug effects ; Humans ; *Tobacco Products/adverse effects ; Reactive Oxygen Species/metabolism ; *Smoke/adverse effects ; *Epithelium, Corneal/metabolism/drug effects/pathology ; Real-Time Polymerase Chain Reaction ; Hot Temperature ; *Cigarette Smoking/adverse effects ; Cell Line ; Proteomics ; },
abstract = {PURPOSE: Tobacco smoke harbors toxic combustion by-products contributing to inflammatory diseases. Cigarette smoke's impact on ocular diseases has been poorly characterized, despite conjunctival mucosa's sensitivity to these toxicants. Of note, cigarette smoke triggers redness, tearing, and discomfort, accounting as a risk factor for glaucoma, macular degeneration, cataracts, and other eye conditions. Low quit rates of cessation highlight the need for alternatives. Heated tobacco products (HTPs), may represent a less toxic alternative for those smokers. This study evaluates cigarette smoke and HTPs effects on cornea under standard and clinically relevant conditions.<br><br>METHODS: Corneal tissues collected from donors and in vitro model in two different cell lines of corneal epithelium were exposed to cigarette (1R6F) smoke and HTPs vapor. Air exposure was included as a control. Tissue pathological evaluation was carried out by hematoxylin and eosin staining. Reactive oxygen species (ROS) were measured, and quantitative PCR assessed inflammatory and antioxidant genes expression. Proteome analysis was used to evaluate differentially expressed proteins related to the oxidative stress. Scratch assay measured smoke and HTPs impact on cells.<br><br>RESULTS: Hematoxylin &amp; eosin staining highlighted that cigarette smoke impairs corneal tissue integrity, leading to ROS accumulation and inflammation, as proved by qPCR analysis. Proteomic analysis showed that corneal tissue's proteins were differently oxidized by the different experimental conditions. HTP targeted structural intracellular proteins, whereas 1R6F affects different members of collagen family. Finally, cigarette smoke, but not HTPs, impairs epithelial cells wound closure.<br><br>CONCLUSIONS: Smoking increases oxidative stress, leading to significant corneal damage and inflammation. HTPs may offer a less toxic alternative.},
}
@article {pmid40166602,
year = {2025},
author = {Emami-Naeini, P and Garmo, V and Boucher, N and Fernando, R and Menezes, A},
title = {Maintaining driving vision after intravitreal anti-VEGF therapy in patients with neovascular AMD and diabetic macular edema: a plain language summary of publication.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414241310274},
doi = {10.1177/25158414241310274},
pmid = {40166602},
issn = {2515-8414},
abstract = {What is this summary about? This is the summary of an article published in Ophthalmology Retina. This summary presents results from a study that used information from a United States (US) healthcare database to look at how intravitreal injections (injections into the eyeball) of anti-vascular endothelial growth factor (anti-VEGF) may affect vision for patients with either neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). The study focused on maintaining driving vision over 4 years. What happened in this study? Researchers looked at information in the Vestrum Health database to identify patients diagnosed with nAMD or DME between January 1, 2014 and June 30, 2019 and had medical records that showed how their vision changed while they were receiving anti-VEGF treatment. What were the results? Vision improved for both nAMD and DME patient groups in the first year of anti-VEGF treatment but then got worse over the next 3 years. Patients with nAMD or DME who had more anti-VEGF injections in the first year of treatment had a higher chance of maintaining their driving vision. Both groups of patients were more likely to lose their driving vision if they were older or had worse vision before starting treatment. What do the results mean? These results show that starting anti-VEGF treatment early and having frequent injections is important for keeping driving vision in patients with nAMD or DME. Currently, patients with nAMD or DME may not be getting injections early and often enough to maintain their driving vision over the long term. Where can I find the original article on which this summary is based? You can read the original article published in the journal Ophthalmology Retina at: https://doi.org/10.1016/j.oret.2023.10.010 Who is this article for? The purpose of this plain language summary is to help patients with either nAMD or DME, their caregivers, patient advocates, healthcare professionals, insurance providers, and policy makers better understand the results of this study. When was this plain language summary of publication written? This summary was drafted in December 2023. Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are among the leading causes of vision loss among individuals aged 50 years and older in the US and worldwide.},
}
@article {pmid40165908,
year = {2025},
author = {Talebi, R and Yu, F and Tseng, VL and Coleman, AL},
title = {Association between Food Insecurity and Chronic Eye Disease in the National Institutes of Health's All of Us Research Program.},
journal = {Ophthalmology science},
volume = {5},
number = {3},
pages = {100697},
pmid = {40165908},
issn = {2666-9145},
abstract = {PURPOSE: Food insecurity is a potential risk factor for visual impairment; however, its association with specific eye diseases remains unknown. This study aims to examine the association between food insecurity and chronic eye diseases including glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and cataracts.<br><br>DESIGN: Cross-sectional.<br><br>PARTICIPANTS: Participants of the All of Us (AoU) Research Program, who had electronic health record data and responded to survey questions regarding food insecurity.<br><br>METHODS: Population-based. Multivariable logistic regression was used to examine associations between food insecurity and each eye disease.<br><br>MAIN OUTCOME MEASURES: Primary outcomes included glaucoma, AMD, DR, or cataracts, based on the International Classification of Disease, 9th and 10th Revision codes.<br><br>RESULTS: A total of 78&#xa0;694 participants were included in the study population. Of these, 9732 (12.4%) reported food insecurity, 2095 (2.7%) had glaucoma, 1398 (1.8%) had AMD, 1127 (1.4%) had DR, and 10&#xa0;135 (12.9%) had cataracts. Compared with those without food insecurity, participants with food insecurity had significantly higher odds of glaucoma (adjusted odds ratio [aOR]: 1.43, 95% confidence interval [CI]: 1.18-1.72, P &#x2264; 0.001) but not of AMD (aOR: 0.91, 95% CI: 0.67-1.21, P&#xa0;=&#xa0;0.544), DR (aOR: 1.15, 95% CI: 0.93-1.42, P&#xa0;=&#xa0;0.180), or cataracts (aOR: 0.97, 95% CI: 0.87-1.08, P&#xa0;=&#xa0;0.635).<br><br>CONCLUSIONS: This study found a positive association between food insecurity and glaucoma in the AoU Research Program. Further research should focus on understanding disease-specific mechanisms for this association. Adequate social determinants of health screening and population interventions to improve stable access to healthy food options may prove vital for reducing the risk of eye disease.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40162950,
year = {2025},
author = {Goerdt, L and Berlin, A and Gao, L and Swain, TA and Kim, SS and McGwin, G and Clark, ME and Kar, D and Owsley, C and Sloan, KR and Curcio, CA},
title = {Topographic Analysis of Two-Wavelength Autofluorescence Supports Higher Macular Xanthophyll Pigment in AMD Than Aging: ALSTAR2 Baseline.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {3},
pages = {61},
pmid = {40162950},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Aged ; Male ; *Macular Pigment/metabolism ; *Macular Degeneration/metabolism/diagnosis ; *Aging/physiology ; *Xanthophylls/metabolism ; Tomography, Optical Coherence/methods ; *Macula Lutea/metabolism/pathology ; Aged, 80 and over ; Optical Imaging/methods ; Fluorescein Angiography/methods ; Middle Aged ; Lutein/metabolism ; },
abstract = {PURPOSE: To advance metabolic imaging of the high-risk macula lutea by quantifying the topography of macular pigment optical density (MPOD), measured with two-wavelength autofluorescence (2WAF), and quantitative (short-wavelength) autofluorescence (qAF) intensity, which share the same signal source and cross-retinal light path, in aging, early (e), and intermediate (i) age-related macular degeneration (AMD).<br><br>METHODS: 2WAF and qAF images of 384 pseudophakic eyes of 230 persons (mean age, 74.2 &#xb1; 5.7 years; 145 female) from ALSTAR2 (AREDS 9-step classification: 170, normal; 118, eAMD; 96 iAMD) were shown as maps (intensity, z-score) and meridian plots. Correlations were determined in Early Treatment Diabetic Retinopathy Study (ETDRS) subfields.<br><br>RESULTS: MPOD was higher in the central subfield (P < 0.01) in iAMD compared to eAMD and normal eyes, and qAF was lower in the central subfield and inner ring (both P < 0.01) in AMD compared to normal eyes. MPOD differed along horizontal versus vertical meridians, depending on disease stage. Pixel-level z-score maps and meridian plots showed distinct annuli of alternating levels of MPOD anchored on the foveal center, unrelated to qAF. Across the central subfield, high 2WAF was associated with low qAF in all disease stages (r = -0.47, r = -0.47, r = -0.42; all P < 0.001). In the inner ring, correlations were significant for normal and eAMD only (r = -0.31, P = 0.004 and r = -0.22, P &#x2264; 0.001, respectively).<br><br>CONCLUSIONS: New analytics support previously reported higher MPOD in AMD compared to normal eyes, especially central subfield and inner ring. MPOD and qAF differ by disease-stage-related topography and correlations, supporting independent use in metabolic imaging of the macula lutea.},
}
@article {pmid40161805,
year = {2025},
author = {Swan, J and Toomey, CB and Bergstrand, M and Cuello, HA and Robie, J and Yu, H and Yuan, Y and Kooner, AS and Chen, X and Shaughnessy, J and Ram, S and Varki, A and Gagneux, P},
title = {The sialome of the retina, alteration in age-related macular degeneration (AMD) pathology and potential impacts on Complement Factor H.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40161805},
issn = {2692-8205},
support = {K08 EY035322/EY/NEI NIH HHS/United States ; R01 AI130684/AI/NIAID NIH HHS/United States ; },
abstract = {PURPOSE: Little is known about sialic acids of the human retina, despite their integral role in self/non-self-discrimination by complement factor H (CFH), the alternative complement pathway inhibitor.<br><br>METHODS: A custom sialoglycan microarray was used to characterize the sialic acid-binding specificity of native CFH or recombinant molecules where IgG Fc was fused to CFH domains 16-20 (contains a sialic acid-binding site), domains 6-7 (contains a glycosaminoglycan-binding site) or the CFH-related proteins (CFHRs) 1 and 3. We analyzed macular and peripheral retinal tissue from post-mortem ocular globes for amount, type, and presentation (glycosidic linkage type) of sialic acid in individuals with age-related macular degeneration (AMD) and age-matched controls using fluorescent lectins and antibodies to detect sialic acid and endogenous CFH. Released sialic acids from neural retina, retinal pigmented epithelium (RPE) cells and the Bruch's membrane (BrM) were labelled with 1,2-diamino-4,5-methylenedioxybenzene-2HCl (DMB), separated and quantified by high-performance liquid chromatography (DMB-HPLC).<br><br>RESULTS: Both native CFH and the recombinant CFH domains 16-20 recognized Neu5Ac and Neu5Gc that is &#x3b1;2-3-linked to the underlying galactose. 4-O-Actylation of sialic acid and sulfation of GlcNAc did not inhibit binding. Different linkage types of sialic acid were localized at different layers of the retina. The greatest density of &#x3b1;2-3-sialic acid, which is the preferred ligand of CFH, did not colocalize with endogenous CFH. The level of sialic acids at the BrM/choroid interface of macula and peripheral retina of individuals with AMD were significantly reduced.<br><br>CONCLUSIONS: The sialome of the human retina is altered in AMD. This can affect CFH binding and consequently, alternative complement pathway regulation.},
}
@article {pmid40159310,
year = {2025},
author = {Wagner, M and Peschel, T and Leutloff, CJ and Rauscher, FG},
title = {'EarlyAMDRate': A grading instrument for OCT-based assessment of early lesions caused by age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {103},
number = {5},
pages = {e318-e331},
pmid = {40159310},
issn = {1755-3768},
support = {497989466//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Aged ; Male ; Female ; *Wet Macular Degeneration/diagnosis ; *Macular Degeneration/diagnosis ; Disease Progression ; Surveys and Questionnaires ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND AND OBJECTIVES: Long before any signs of age-related macular degeneration (AMD) become clinically noticeable, the disease starts with accumulation of deposits of extracellular debris and formation of lesions within the outermost layers of the retina. For a reliable imaging of lesions in these early stages, optical coherence tomography (OCT) turned out to be largely preferable to colour fundus photography. However, an adequate grading instrument for Early-AMD lesions within OCT data is missing in the literature as yet. The present paper aims to fill this gap.<br><br>METHODS: 'EarlyAMDRate', an instrument for OCT-based grading of Early-AMD lesions, is presented and documented. It comprises a questionnaire assessing a given lesion with respect to its relative position and interaction with the surrounding retinal layers, its brightness, special properties and state of progression (if applicable). Furthermore, the grading procedure includes a graphical masking of the lesion within the OCT image.<br><br>RESULTS: For a consecutive sample of N&#x2009;=&#x2009;100 Early-AMD patients, the 'EarlyAMDRate' grading instrument has been applied to leading OCT scans. Examples of masked lesions and processed grading questionnaires are provided. Both raw lesion diameters and cutting sizes follow a log-normal sample distribution.<br><br>CONCLUSIONS: 'EarlyAMDRate' allows for unprecedented detail of description for single Early-AMD lesions which is adequate to the precision of underlying OCT imaging. The obtained grading information allows for a tracking of single lesions and their properties over time as well as for the generation of well-differentiated metric phenotypes for description of Early-AMD.},
}
@article {pmid40158818,
year = {2025},
author = {Wang, Z and Zhang, Y and Xu, C and Peng, A and Qin, H and Yao, K},
title = {Advancements in age-related macular degeneration treatment: From traditional anti-VEGF to emerging therapies in gene, stem cell, and nanotechnology.},
journal = {Biochemical pharmacology},
volume = {236},
number = {},
pages = {116902},
doi = {10.1016/j.bcp.2025.116902},
pmid = {40158818},
issn = {1873-2968},
mesh = {Humans ; *Macular Degeneration/therapy/genetics/metabolism ; *Genetic Therapy/methods/trends ; Animals ; *Stem Cell Transplantation/methods/trends ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Nanotechnology/methods/trends ; Drug Delivery Systems/methods/trends ; *Angiogenesis Inhibitors/administration &amp; dosage ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults and is projected to affect approximately 400 million individuals worldwide by 2040. Its pathological characteristics include retinal extracellular deposits, such as drusen, which trigger photoreceptor degeneration and damage to the retinal pigment epithelium (RPE), resulting in irreversible vision loss. The pathogenesis of AMD involves genetic, environmental, and aging-related factors. Anti-vascular endothelial growth factor (anti-VEGF) therapy for wet AMD significantly inhibits choroidal neovascularization and delays visual deterioration. However, its high cost, frequent injections, and poor patient compliance limit application, and there remains no effective intervention for dry AMD. In recent years, emerging strategies, such as gene therapy, stem cell therapy, and nanotechnology-based drug delivery systems, offer hope for slowing disease progression by improving targeting, drug stability, and reducing treatment frequency. Nanoparticles, including polymeric and lipid systems, have shown promise for enhancing drug delivery and bioavailability, particularly for dry AMD, where existing therapies are inadequate. These strategies also have the potential to improve patient compliance. This review summarizes AMD epidemiology and examines the limitations of current therapies. It emphasizes the mechanisms and clinical advancements of gene therapy, stem cell therapy, and nanotechnology in AMD treatment. These emerging technologies offer promising opportunities for precision medicine and lay a solid foundation for the future development of multifaceted therapeutic strategies.},
}
@article {pmid40157546,
year = {2025},
author = {Carlà, MM and Ripa, M and Crincoli, E and Catania, F and Rizzo, S},
title = {The spectrum of microcystic macular edema: Pathogenetic insights, clinical entities, and functional prognosis.},
journal = {Survey of ophthalmology},
volume = {70},
number = {5},
pages = {982-994},
doi = {10.1016/j.survophthal.2025.03.010},
pmid = {40157546},
issn = {1879-3304},
mesh = {Humans ; *Macular Edema/diagnosis/etiology/physiopathology/epidemiology ; Prognosis ; Tomography, Optical Coherence/methods ; Visual Acuity/physiology ; },
abstract = {Microcystic macular edema (MME) is the presence of small cystoid abnormalities localized in the inner nuclear layer of the retina. First identified in the context of multiple sclerosis, successive reports highlighted the presence of microcystic changes in several optic nerve conditions, such as neuromyelitis optica, optic atrophy from several etiologies, medical retinal diseases such as age-related macular degeneration and diabetic retinopathy, and in the postoperative period after epiretinal membrane peeling. Generally, these cysts are not associated with vascular leakage, unlike the more conventional types of macular edema from vascular origin. A number of theories have been proposed to explain these findings: the suspect of neuronal loss as causative finding made the hypothesis of retrograde trans-synaptic degeneration likely, more recently flanked by theories including the presence of vitreomacular traction and Müller cells dysfunction. We gather all the insights regarding the pathogenesis, epidemiology and functional impact of MME.},
}
@article {pmid40157129,
year = {2025},
author = {Ottensmann, L and Tabassum, R and Ruotsalainen, SE and Gerl, MJ and Klose, C and McCartney, DL and Widén, E and , and Simons, K and Ripatti, S and Vitart, V and Hayward, C and Pirinen, M},
title = {Examining the link between 179 lipid species and 7 diseases using genetic predictors.},
journal = {EBioMedicine},
volume = {114},
number = {},
pages = {105671},
pmid = {40157129},
issn = {2352-3964},
mesh = {Humans ; Genome-Wide Association Study ; *Genetic Predisposition to Disease ; *Lipids/blood/genetics ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Male ; Female ; *Lipid Metabolism/genetics ; Finland ; Middle Aged ; Risk Factors ; Multifactorial Inheritance ; },
abstract = {BACKGROUND: Genome-wide association studies of lipid species have identified several loci shared with various diseases, however, the relationship between lipid species and disease risk remains poorly understood. Here we investigated whether the plasma levels of lipid species are causally linked to disease risk.<br><br>METHODS: We built genetic predictors of 179 lipid species, measured in 7174 Finnish individuals, by utilising either 11&#xa0;high-impact genomic loci or genome-wide polygenic scores (PGS). We assessed the impact of the lipid species on seven diseases by performing disease association across FinnGen (n&#xa0;=&#xa0;500,348), UK Biobank (n&#xa0;=&#xa0;420,531), and Generation Scotland (n&#xa0;=&#xa0;20,032). We performed univariable Mendelian randomisation (MR) and multivariable MR (MVMR) analyses to examine whether lipid species impact disease risk independently of standard lipids.<br><br>FINDINGS: PGS explained >4% of the variance for 34 lipid species but variants outside the high-impact loci had only a marginal contribution. Variants within the high-impact loci showed association with all seven diseases. MVMR supported a causal role of ApoB in ischaemic heart disease after accounting for lipid species. Phosphatidylethanolamine-increasing LIPC variants seemed to lower age-related macular degeneration risk independently of HDL-cholesterol. MVMR suggested a protective effect of four lipid species containing arachidonic acid on cholelithiasis risk independently of Total Cholesterol.<br><br>INTERPRETATION: Our study demonstrates how genetic predictors of lipid species can be utilised to gain insights into disease risk. We report potential links between lipid species and age-related macular degeneration and cholelithiasis risk, which can be explored for their utility in disease risk prediction and therapy.<br><br>FUNDING: The funders had no role in the study design, data analyses, interpretation, or writing of this article.},
}
@article {pmid40155536,
year = {2025},
author = {Wang, J and Han, J and Wang, X and Han, W},
title = {The global burden and attributable risk factor analysis of age-related macular degeneration in 204 countries and territories, 1990-2021.},
journal = {Eye (London, England)},
volume = {39},
number = {9},
pages = {1860-1867},
pmid = {40155536},
issn = {1476-5454},
support = {82271074//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology ; Risk Factors ; Female ; Male ; Aged ; Global Burden of Disease/trends ; *COVID-19/epidemiology ; Disability-Adjusted Life Years/trends ; Global Health/statistics &amp; numerical data ; Middle Aged ; Aged, 80 and over ; SARS-CoV-2 ; Quality-Adjusted Life Years ; Age Distribution ; },
abstract = {OBJECTIVES: To report the global burden of age-related macular degeneration (AMD) and associated risk factors between 1990 and 2021 by age, sex, and sociodemographic index (SDI) and to investigate the influence of the COVID-19 pandemic on AMD burden.<br><br>METHODS: Data on disability-adjusted life years (DALYs) of AMD were obtained from the Global Burden of Disease Study 2021. Joinpoint regression determined annual percentage change (APC) and average annual percentage change (AAPC). ARIMA model projected AMD burden trends, with additional analyses for frontier, decomposition, and health inequality.<br><br>RESULTS: Globally, AMD accounted for 578.02 (95% UI: 401.24-797.57) thousand DALYs in 2021, driven by population growth and aging. Age-standardized DALY rates (ASDRs) fell from 1990 to 2021 (AAPC: -0.69, 95%CI: -0.77 to -0.6), but increased in high-middle and middle SDI regions during the initial two years of the pandemic. ARIMA model forecasts a worldwide decline in ASDRs over the next 29 years. Sex disparities were significant, with women having continuously higher ASDRs, especially from 2019 to 2021. Despite some reduction in health inequality, an inverse SDI-ASDR relationship indicated ongoing socioeconomic disparities. Frontier analysis showed improvement potential across growth stages. Smoking-related AMD burden decreased globally, with a correlation between national ASDRs and PM2.5 levels.<br><br>CONCLUSIONS: ASDRs due to AMD have decreased over the past 32 years, while DALYs have substantially increased. The burden is more heavily tilted toward women, the elderly, and less-developed countries, with COVID-19 further intensifying the situation. Addressing the burden requires focusing on smoking cessation and air quality improvements.},
}
@article {pmid40152815,
year = {2025},
author = {Lockhart, CM and Barakat, MR and Dunn, JD and Richardson, T and Bratcher, T and Greene, E and Kobernick, M and Schneider, D and Wigginton, J},
title = {Transforming retinal disease management through diabetes care.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {31},
number = {4-a Suppl},
pages = {S1-S11},
pmid = {40152815},
issn = {2376-1032},
mesh = {Humans ; *Diabetic Retinopathy/drug therapy/economics ; Disease Management ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Health Services Accessibility ; *Diabetes Mellitus/drug therapy/economics ; Angiogenesis Inhibitors/therapeutic use/economics ; *Retinal Diseases/drug therapy/economics/therapy ; },
abstract = {In September 2024, AMCP and Impact Education, LLC, held a virtual Market Insights summit with chief medical and pharmacy officers and other senior health care executives to discuss the management of retinal diseases in patients with diabetes. The summit aimed to explore the impact of current policies on treatment access and costs, identify best practices for anti-vascular endothelial growth factor (anti-VEGF) coverage, and address barriers related to social determinants of health (SDOH). Anti-VEGF therapy, although effective for conditions such as diabetic macular edema and age-related macular degeneration, may require monthly injections that impose a significant burden on patients and caregivers, affecting adherence and outcomes. Key topics included examining the impact of current policies on treatment access and total cost of care, exploring opportunities for management of patients at increased risk for blindness, outlining the benefits of durable treatment approaches, addressing strategies to overcome access barriers related to SDOH, and identifying best practices in coverage policies for anti-VEGF agents. Strategies for addressing barriers to care were explored, including the potential use of gold carding, contingent on establishing clearer definitions of good care in retinal disease management, understanding prescribing variation, gaining standardized of definitions or guidelines for good" care, and practical strategies for using extended dosing to support adherence and access. Health care executives reached agreement on the central role of ophthalmologists in preventing blindness in patients with diabetes and retinal diseases and the importance of timely access to appropriate treatments.},
}
@article {pmid40152761,
year = {2025},
author = {Marmalidou, A and Siddiqui, H and Jamil, MU and Woo, KM and Yaghy, A and Alibhai, AY and Takahashi, H and Kaiser, S and Effert, K and Zhao, PY and Desai, SJ and Robinson, CC and Duker, JS and Waheed, NK},
title = {Comparison Between MAIA and MP-3 In Healthy Subjects and Patients With Diabetes, Diabetic Retinopathy, and Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {3},
pages = {59},
pmid = {40152761},
issn = {1552-5783},
mesh = {Healthy Volunteers ; *Diabetic Retinopathy/diagnosis/physiopathology ; *Macular Degeneration/diagnosis/physiopathology ; Cross-Sectional Studies ; *Diabetes Mellitus/physiopathology ; Macula Lutea/diagnostic imaging/physiopathology ; Linear Models ; Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; *Visual Field Tests/instrumentation/methods/statistics &amp; numerical data ; Fundus Oculi ; *Scotoma/diagnosis/physiopathology ; Young Adult ; Aged, 80 and over ; Visual Fields/physiology ; },
abstract = {PURPOSE: The purpose of this study was to assess the comparability of mean sensitivity (MS) values obtained using the Macular Integrity Assessment (MAIA; CenterVue S.p.A. [iCare], Padova, Italy) and Microperimeter-3 (MP-3; NIDEK CO., Ltd., Gamagori, Japan) microperimetry (MP) devices.<br><br>METHODS: This cross-sectional study includes subjects with healthy eyes, eyes with diabetes mellitus without diabetic retinopathy (DM no DR), diabetic retinopathy (DR), and non-exudative age-related macular degeneration (AMD). Patients underwent testing on both MAIA and MP-3 MP devices, using a 10-2 macular grid with 68 stimuli and identical parameters. A diagnosis-adjusted linear regression model and mixed modeling mapped MP-3 MS to MAIA MS and Bland-Altman analysis were used to assess the agreement.<br><br>RESULTS: One hundred eleven eyes (43 healthy eyes, 14 eyes with DM no DR, 32 eyes with DR, and 22 eyes with AMD) from 80 subjects (age = 57.2 &#xb1; 20.3&#xa0;years) were enrolled. MAIA consistently showed higher MS than MP-3. The MP-3 device detected absolute scotomatous points in more eyes than MAIA (6 eyes [MAIA] vs. 10 eyes [MP-3]). Healthy eyes exhibited stronger agreements than those with DR (P < 0.001) or AMD (P = 0.015). Converting MP-3 to MAIA MS improved agreement and reduced coefficients of repeatability (CoRs) but did not fully account for inter-device variability. MP-3 classified more eyes as having relatively unstable or unstable fixation than MAIA (P = 0.014).<br><br>CONCLUSIONS: Both devices effectively detect retinal functional changes and scotomas. The conversion methods developed in this study can aid cross-device comparisons, but retinal pathologies (DM and AMD) introduce additional inter-device variability. Future studies incorporating multiple devices should account for this variability in their study design.},
}
@article {pmid40152631,
year = {2025},
author = {Cushley, LN and McCann, R and Moutray, T and Silvestri, G and Peto, T and Jackson, AJ},
title = {Trends in Adult Visual Impairment Certification in Northern Ireland: A 10-Year Analysis.},
journal = {Ophthalmic epidemiology},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/09286586.2025.2483697},
pmid = {40152631},
issn = {1744-5086},
abstract = {Purpose: In the UK, people are certified as severely sight impaired (SSI) or sight impaired (SI) according to Government guidelines. Certification ensures people with visual impairments can access adequate support and benefits. Certification of visual impairment data has been collected and analysed in Northern Ireland by a team and full continuous data is available from 2014 to 2023.Methods: Data from certification forms was collected, entered into an Excel spreadsheet, and 10% was validated by the certification of visual impairment team. This data was collated, cleaned and analysed using IBM SPSS (version 27) for frequency, mean, median and interquartile ranges.Results: Results show that over a 10-year period (2014-2023) the number of certifications in Northern Ireland has increased to a point where they are aligned with figures from other regions of the United Kingdom (UK). Results show that more people are certified as SSI than SI in Northern Ireland (NI) which is in contrast to figures reported in England and Wales. More females are certified than males in NI. Similarly to England and Wales, the most common cause of certification of visual impairment in adults in NI is Age-Related Macular Degeneration, accounting for around 50% of certifications annually. The second most common cause is glaucoma followed by diabetic eye disease (DED). In working age adults, DED is the leading cause of certification.Conclusion: The results from 10 years of certification data in NI show common themes with other high-income countries, including increased certification, particularly among females, and the most common causes of certification remain AMD, glaucoma and DED.},
}
@article {pmid40152567,
year = {2025},
author = {Edwards, G and Riordan, SM and Buchholz, C and Mardelli, M and Euritt, CP and Perez-Magnelli, R and Rafiq, A and Engelmeyer, A and Koulen, P},
title = {Stratification of the Extent of Visual Impairment Identifies Sex-Specific Degenerative Changes in Retinal Structure and Function during Aging.},
journal = {Journal of integrative neuroscience},
volume = {24},
number = {3},
pages = {25805},
pmid = {40152567},
issn = {0219-6352},
support = {R01 EY030747/EY/NEI NIH HHS/United States ; //Felix and Carmen Sabates Missouri Endowed Chair in Vision Research/ ; EY030747//National Eye Institute of the National Institutes of Health (PK)/ ; //Vision Research Foundation of Kansas City/ ; },
mesh = {Animals ; Male ; Female ; *Aging/physiology/pathology ; Mice, Inbred C57BL ; *Contrast Sensitivity/physiology ; Electroretinography ; *Retina/pathology/physiopathology ; Mice ; *Sex Characteristics ; *Visual Acuity/physiology ; *Vision Disorders/physiopathology/pathology ; Longitudinal Studies ; *Retinal Degeneration/physiopathology/pathology ; },
abstract = {BACKGROUND: Initial manifestations of neurodegenerative ocular conditions, including age-related macular degeneration (AMD) and glaucoma, often remain undetected in the early stages and can begin after the age of 50 years with the likelihood gradually increasing each year thereafter. This study aimed to explore variances in visual and retinal function and anatomy among C57BL/6J mice, aiming to pinpoint differences between biological age and sex factors that potentially lead to the onset of vision impairment.<br><br>METHODS: A longitudinal study evaluated visual acuity (VA) and contrast sensitivity (CS) using optomotor reflex (OMR), and retinal function, encompassing scotopic and photopic measurements, was recorded by electroretinogram (ERG) at 12 months of age. Tissue was subsequently harvested for histological analysis, complementing the in vivo findings. Disparities in visual function were observed between individual male and female mice, necessitating categorization of visual impairment levels to investigate further sex-specific differences in the study's aging population. Comparisons between sex and the degree of visual impairment were conducted using ANOVA followed by Tukey's or Bonferroni's post-hoc corrections and unpaired t-tests. Pearson correlation analysis determined the association between biological factors.<br><br>RESULTS: Sex-related disparities were found in the visual function of male (n = 13) and female (n = 18) mice aged 5-12 months. Eyes were categorized by vision impairment: normal vision, or low, moderate, or severe vision loss at the end of the study. Male and female mice differed in mean contrast sensitivity, indicating less sensitivity to fine detail and moving stimuli in female mice (11-12 months old, p < 0.001). Spectral-domain optical coherence tomography (SD-OCT) revealed a thinner retinal outer nuclear layer in male mice (p < 0.0001), although this did not vary across different levels of vision impairment. ERG indicated slower retinal responses in male mice (p < 0.05), while histology showed a significant reduction in the inner plexiform layer thickness in male mice with severe vision loss (p < 0.0001). Conversely, female mice exhibited greater thinning in the photoreceptor layer when vision was unimpaired (p < 0.01).<br><br>CONCLUSIONS: The study shows that sex and extent of vision impairment influence visual and retinal health, with individual retinal layers differentially changing in thickness over time.},
}
@article {pmid40151609,
year = {2025},
author = {Won, JH and Sitnikov, D and Hong, J},
title = {Protective effects of carotenoids against blue light induced-cellular damage in human retinal pigment epithelium.},
journal = {Food science and biotechnology},
volume = {34},
number = {8},
pages = {1713-1723},
pmid = {40151609},
issn = {2092-6456},
abstract = {UNLABELLED: The retinal pigmented epithelium (RPE) is constantly exposed to visible light, including blue light (BL) that creates reactive oxygen species (ROS), which are harmful to DNA and induce cellular senescence. Carotenoids are recognized for their antioxidant properties, but their protective effect on DNA repair and cellular senescence under BL induced oxidative stress has not been evaluated. After BL irradiation, the positive senescence-associated-β-galactosidase (SA-β-gal) staining, and gene expression of p16 [INK4a] and p21 [Waf/Cip1] were upregulated in ARPE-19 cells. Pretreatment with carotenoids reduced ROS, p-H2A.X nuclear foci, and SA-β-gal positive cells induced by BL irradiation. Furthermore, pretreatment with carotenoids reduced the secretion of IL-6 and VEGF triggered by BL. Since increased senescent cells and secretion of IL-6 and VEGF are involved in age-related macular degeneration pathogenesis, our results support that carotenoid supplementation has a potential role in protecting the eyes from the deleterious effects of excessive BL exposure.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-024-01757-z.},
}
@article {pmid40151374,
year = {2025},
author = {Yorston, D},
title = {Age-related macular degeneration (AMD): an introduction.},
journal = {Community eye health},
volume = {37},
number = {125},
pages = {7-8},
pmid = {40151374},
issn = {0953-6833},
}
@article {pmid40151373,
year = {2025},
author = {Piyasena, MP and Dhanapala, M},
title = {Availability and affordability of anti-VEGF biosimilars for the treatment of age-related macular degeneration and diabetic macular oedema in Sri Lanka.},
journal = {Community eye health},
volume = {37},
number = {125},
pages = {24-25},
pmid = {40151373},
issn = {0953-6833},
}
@article {pmid40150743,
year = {2025},
author = {Li, Z and Hu, Z and Gao, Z},
title = {Advances in the Study of Age-Related Macular Degeneration Based on Cell or Cell-Biomaterial Scaffolds.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {3},
pages = {},
pmid = {40150743},
issn = {2306-5354},
support = {2022YFF1202901//National Key Research and Development Program of China/ ; },
abstract = {Age-related macular degeneration (AMD), a progressive neurodegenerative disorder affecting the central retina, is pathologically defined by the irreversible degeneration of photoreceptors and retinal pigment epithelium (RPE), coupled with extracellular drusen deposition and choroidal neovascularization (CNV), and AMD constitutes the predominant etiological factor for irreversible vision impairment in adults aged ≥60 years. Cell-based or cell-biomaterial scaffold-based approaches have been popular in recent years as a major research direction for AMD; monotherapy with cell-based approaches typically involves subretinal injection of progenitor-derived or stem cell-derived RPE cells to restore retinal homeostasis. Meanwhile, cell-biomaterial scaffolds delivered to the lesion site by vector transplantation have been widely developed, and the implanted cell-biomaterial scaffolds can promote the reintegration of cells at the lesion site and solve the problems of translocation and discrete cellular structure produced by cell injection. While these therapeutic strategies demonstrate preliminary efficacy, rigorous preclinical validation and clinical trials remain imperative to validate their long-term safety, functional durability, and therapeutic consistency. This review synthesizes current advancements and translational challenges in cell-based and cell-biomaterial scaffold approaches for AMD, aiming to inform future development of targeted interventions for AMD pathogenesis and management.},
}
@article {pmid40150102,
year = {2025},
author = {Lee, CY and Yang, SF and Mai, EL and Huang, JY and Yeh, CB and Chang, CK},
title = {The Relationship Between Aortic Stenosis and the Possibility of Subsequent Macular Diseases: A Nationwide Database Study.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
pmid = {40150102},
issn = {2075-4418},
abstract = {Objectives: This study aimed to investigate the possible relationship between aortic stenosis (AS) occupancy and the incidence of subsequent macular diseases. Methods: A retrospective cohort study was conducted using the TriNetX database, and participants with AS were enrolled and matched to non-AS participants. A total of 421,860 and 421,860 participants were evenly divided into the AS and non-AS groups, respectively. The major outcomes of the present study include the development of age-related macular degeneration (AMD), retinal vascular occlusion (RVO), epiretinal membrane (ERM), and central serous chorioretinopathy (CSC). Cox proportional hazard regression was utilized for statistical analysis. Results: There were 4426 and 3013 AMD events; 7315 and 4753 RVO events; 2780 and 1910 ERM events; and 113 and 64 CSC events in the AS and non-AS groups, respectively. According to the results of Cox proportional hazard regression analysis, the AS group demonstrated significantly higher incidences of all macular diseases, including AMD, RVO, ERM, and CSC, compared to the non-AS group (all p < 0.05). The cumulative probabilities of all macular diseases were significantly higher in the AS group than in the non-AS group (all p < 0.05). In the sensitivity analysis, the developmental risks of AMD were significantly higher in the AS group than in the non-AS group with all traits. Conclusions: This study determined that AS occupancy is related to a higher risk of developing macular diseases, which positively correlated to the disease time of AS.},
}
@article {pmid40149615,
year = {2025},
author = {Wei, P and Gao, S and Han, G},
title = {Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis.},
journal = {Biomedicines},
volume = {13},
number = {3},
pages = {},
pmid = {40149615},
issn = {2227-9059},
support = {Grant No.82301240//National Natural Science Foundation of China/ ; Grant No. TJWJ2023MS0036//Tianjin Health Research Project/ ; TJYXZDXK-016A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; },
abstract = {Background/Objectives: Despite substantial research, the causal relationships between gut microbiota (GM) and age-related macular degeneration (AMD) remain unclear. We aimed to explore these causal associations using Mendelian randomization (MR) and elucidate the potential mechanisms mediated by blood metabolites. Methods: We utilized the 211 GM dataset (n = 18,340) provided by the MiBioGen consortium. AMD outcome data were sourced from the MRC Integrated Epidemiology Unit (IEU) OpenGWAS Project. We performed bidirectional MR, two mediation analyses, and two-step MR to assess the causal links between GM and different stages of AMD (early, dry, and wet). Results: Our findings indicate that the Bacteroidales S24.7 group and genus Dorea are associated with an increased risk of early AMD, while Ruminococcaceae UCG011 and Parasutterella are linked to a higher risk of dry AMD. Conversely, Lachnospiraceae UCG004 and Anaerotruncus are protective against dry AMD. In the case of wet AMD, Intestinimonas and Sellimonas increase risk, whereas Anaerotruncus and Rikenellaceae RC9 reduce it. Additionally, various blood metabolites were implicated: valine, arabinose, creatine, lysine, alanine, and apolipoprotein A1 were associated with early AMD; glutamine and hyodeoxycholate-with a reduced risk of dry AMD; and androsterone sulfate, epiandrosterone sulfate, and lipopolysaccharide-with a reduced risk of wet AMD. Notably, the association between family Oxalobacteraceae and early AMD was mediated by valine, accounting for 19.1% of the association. Conclusions: This study establishes causal links between specific gut microbiota and AMD, mediated by blood metabolites, thereby enhancing our understanding of the gut-retina axis in AMD pathophysiology.},
}
@article {pmid40149498,
year = {2025},
author = {Abu-Amero, KK and Almadani, B and Abualkhair, S and Hameed, S and Kondkar, AA and Sollazzo, A and Yu, AC and Busin, M and Zauli, G},
title = {Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review.},
journal = {Genes},
volume = {16},
number = {3},
pages = {},
pmid = {40149498},
issn = {2073-4425},
mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Eye Diseases/genetics/pathology ; Mitochondria/genetics/pathology/metabolism ; Mutation ; *Mitochondrial Diseases/genetics ; },
abstract = {Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber's hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA's variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases.},
}
@article {pmid40148774,
year = {2025},
author = {Cao, X and Xu, Z and Zhang, B and Jiang, Z and Yuan, X},
title = {Exploring causal relationships between circulating micronutrients and age-related eye diseases: a Mendelian randomization study.},
journal = {Genes &amp; nutrition},
volume = {20},
number = {1},
pages = {8},
pmid = {40148774},
issn = {1555-8932},
support = {82371033, 81970772, 32200684//National Natural Science Foundation of China/ ; 82371033, 81970772, 32200684//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: With the global population aging, age-related eye diseases (AREDs) such as senile cataract (SC), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR) are becoming increasingly significant public health concerns. The rising prevalence of AREDs underscores the urgent need for effective prevention and treatment strategies. This study aimed to explore the causal relationships between circulating micronutrients (CMs) and AREDs.<br><br>METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted using genetic variants as instrumental variables to assess the effects of fifteen CMs (vitamin A, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, folate, carotene, copper, calcium, iron, magnesium, potassium, selenium, zinc) on AREDs. Data were sourced from large-scale genome-wide association studies (GWAS). The primary analytical method employed was inverse-variance weighted (IVW), supplemented by sensitivity analyses to confirm the robustness of the results.<br><br>RESULTS: The MR analysis revealed significant protective effects of selenium against SC (OR&#x2009;=&#x2009;0.961, 95% CI&#x2009;=&#x2009;0.932-0.991, P&#x2009;=&#x2009;0.012) and DR (OR&#x2009;=&#x2009;0.927, 95% CI&#x2009;=&#x2009;0.870-0.987, P&#x2009;=&#x2009;0.019). Furthermore, higher genetically predicted magnesium levels were associated with a reduced risk of AMD (OR&#x2009;=&#x2009;0.679, 95% CI&#x2009;=&#x2009;0.515-0.895, P&#x2009;=&#x2009;0.006). However, no significant causal relationships were observed between the other CMs and glaucoma or other AREDs.<br><br>CONCLUSIONS: These findings provided valuable insights into the complex interplay between CMs and AREDs, offering potential pathways for developing targeted nutritional interventions and public health strategies to mitigate the risk of these debilitating conditions.},
}
@article {pmid40148491,
year = {2025},
author = {Veuskens, BRJ and Brouwer, MC and van Mierlo, G and Geissler, J and van Leeuwen, K and Derlagen, M and Keijzer, NCH and Hoogenboezem, M and Kuijpers, TW and Pouw, RB},
title = {Factor H-related 2 levels dictate FHR dimer composition.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {10669},
pmid = {40148491},
issn = {2045-2322},
support = {899163//European Union's Horizon 2020 research and innovation programme/ ; SRF-YIA-23-06//Sanquin Research Fund/ ; },
mesh = {Humans ; *Protein Multimerization ; *Complement C3b Inactivator Proteins/metabolism/genetics/chemistry ; Enzyme-Linked Immunosorbent Assay ; *Eye Proteins/metabolism/chemistry/genetics ; },
abstract = {Factor H-related (FHR) protein 1 and 2 form dimers resulting in FHR-1 and -2 homodimers, and FHR-1/2 heterodimers. Dimerization is hypothesized to further increase their antagonistic function with complement regulator factor H (FH). So far, only FHR-1 homodimers and FHR-1/2 heterodimers could be quantified in a direct way. With the reported genetic associations between CFHR2 and complement-related diseases such as age related macular degeneration and C3-glomerulopathy, direct assessment of FHR-2/2 levels determining the dimer distribution of FHR-1 and -2 is needed to further elucidate their role within complement regulation. Therefore, novel in-house generated FHR-2 antibodies were used to develop a specific ELISA to enable direct quantification of FHR-2 homodimers. Allowing for the first time the accurate measurement of all FHR-1 and -2 containing dimers in a large cohort of healthy donors. By using native FHR-1 and -2 or deficient plasma, we determined the stability, kinetics and distribution of FHR-1 and -2 dimers. Additionally, we show how genetic variants influence dimer levels. Our results confirm a rapid, dynamic, dimer formation in plasma and show FHR-1/2 dimerization rearches a distribution equilibrium that is limited by the relative low levels of FHR-2 in relation to its dimerization partner FHR-1.},
}
@article {pmid40148458,
year = {2025},
author = {Kim, Y and Han, K and Kim, JH},
title = {Prevalence and risk factors of undiagnosed age-related macular degeneration: the Korea National Health and Nutrition Examination Survey 2017-2020.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {10647},
pmid = {40148458},
issn = {2045-2322},
mesh = {Humans ; Republic of Korea/epidemiology ; Male ; Female ; Risk Factors ; Middle Aged ; Prevalence ; Aged ; Nutrition Surveys ; *Macular Degeneration/epidemiology/diagnosis ; Cross-Sectional Studies ; Adult ; Aged, 80 and over ; },
abstract = {This study aimed to evaluate the prevalence and risk factors for undiagnosed age-related macular degeneration (AMD) in the Korean population. This cross-sectional study utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES 2017-2020), which included a total of 13,737 subjects of 40 years or older. Cases in which AMD was identified through imaging interpretation of the KNHANES data, but the patients had not received a prior medical diagnosis of AMD, were classified as undiagnosed AMD. The prevalence and risk factors for undiagnosed AMD were analyzed. Among the patients identified to having AMD through KNHANES, the prevalence of undiagnosed AMD was 95.25% (95% confidence interval [CI], 94.13-96.37). Multivariate analysis revealed that a low level of education was significantly associated with a higher risk of undiagnosed AMD (p = 0.0066). A low level of education was also linked to a higher risk of undiagnosed early AMD (p = 0.0369) and neovascular AMD (p = 0.0399). Aging was strongly associated with an increased risk of undiagnosed geographic atrophy (p < 0.0001). Physical activity was associated with a lower risk of undiagnosed neovascular AMD (p = 0.0107). The high prevalence of undiagnosed AMD in the Korean population highlights the need for regular fundus examinations to facilitate accurate detection of AMD. Low education level emerged as a significant risk factor for undiagnosed AMD, emphasizing the importance of targeted interventions for this population to reduce the risk of visual impairment due to AMD.},
}
@article {pmid40147376,
year = {2025},
author = {Baillif, S and Nahon-Esteve, S and Pace-Loscos, T and Pagès, G and Dufies, M},
title = {Aqueous humor mediator levels as biomarkers of anti-VEGF response in age-related macular degeneration.},
journal = {Cytokine},
volume = {190},
number = {},
pages = {156921},
doi = {10.1016/j.cyto.2025.156921},
pmid = {40147376},
issn = {1096-0023},
mesh = {Humans ; *Aqueous Humor/metabolism ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Male ; Female ; Aged ; *Biomarkers/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Intravitreal Injections ; Aged, 80 and over ; Prospective Studies ; Angiogenesis Inhibitors/therapeutic use ; Visual Acuity ; Middle Aged ; },
abstract = {PURPOSE: To monitor intraocular mediator dynamics in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with anti-VEGF intravitreal injections (IVIs) to identify individual mediator patterns correlating with treatment response.<br><br>DESIGN: Interventional, monocentric, prospective, clinical study.<br><br>PARTICIPANTS: Treatment-na&#xef;ve nAMD patients.<br><br>METHODS: Aqueous humor samples (100-200&#xa0;&#x3bc;L) were collected by clear cornea paracentesis at baseline (before the first anti-VEGF IVI) and before the second and third anti-VEGF IVIs. The levels of 13 intraocular mediators were measured (VEGF-A, VEGF-C, PlGF, IL-1&#x3b2;, IL-6, IL-10, IL-18, CXCL1, CXCL5, CXCL7, CXCL8, MIP-1&#x3b1; and TNF&#x3b1;) using multiplex arrays.<br><br>MAIN OUTCOMES MEASURES: The primary endpoint was the changes in intraocular inflammatory mediator levels between baseline and month 3. Secondary endpoints were the changes in best-corrected visual acuity (BCVA) and Central Retinal Thickness (CRT) between baseline and month 4.<br><br>RESULTS: Fifteen eyes were included in the study. BCVA remained stable throughout the study (p&#xa0;=&#xa0;0.07). CRT, foveal thickness, and the presence of intraretinal and subretinal fluid significantly decreased after anti-VEGF IVIs (p&#xa0;<&#xa0;0.0001, p&#xa0;<&#xa0;0.0001, p&#xa0;<&#xa0;0.001 and p&#xa0;<&#xa0;0.001, respectively). After anti-VEGF IVIs, VEGF-A levels significantly decreased (p&#xa0;<&#xa0;0.0001). No significant differences in all other mediator levels were observed. Three patients had baseline VEGF-A levels &#x2264;50&#xa0;pg/mL: they showed higher baseline IL-6 levels (p&#xa0;=&#xa0;0.05), and elevated IL-6 (p&#xa0;=&#xa0;0.03), PlGF (p&#xa0;=&#xa0;0.02), VEGF-C (p&#xa0;=&#xa0;0.005), IL-8 (p&#xa0;=&#xa0;0.04), and TNF&#x3b1; (p&#xa0;=&#xa0;0.013) levels after the first IVI. Good clinical responders had significantly higher baseline VEGF-A levels (p&#xa0;=&#xa0;0.007). Patients who required a fourth IVI within 8&#xa0;weeks of the loading dose had higher baseline TNF&#x3b1; levels (p&#xa0;=&#xa0;0.05); higher MIP-1&#x3b1; levels after the first IVI (p&#xa0;=&#xa0;0.045); and elevated TNF&#x3b1; (p&#xa0;=&#xa0;0.026) and IL-8 (p&#xa0;=&#xa0;0.029) levels after the second IVI.<br><br>CONCLUSIONS: The aqueous humor levels of the studied mediators remained stable after anti-VEGF IVIs, except for a significant decrease in VEGF-A levels in all patients. Patients with low baseline intraocular VEGF-A levels (i.e., &#x2264;50&#xa0;pg/mL) showed an intraocular inflammatory profile with elevated IL-6, PlGF, VEGF-C, IL-8 and TNF&#x3b1; levels. Treatment response correlated with high baseline VEGF-A levels. An interval&#xa0;>&#xa0;8&#xa0;weeks between the third and fourth anti-VEGF IVIs was associated with a pro-angiogenic/pro-inflammatory environment.},
}
@article {pmid40146150,
year = {2025},
author = {Aresta, G and Araújo, T and Schmidt-Erfurth, U and Bogunovic, H},
title = {Anomaly Detection in Retinal OCT Images With Deep Learning-Based Knowledge Distillation.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {3},
pages = {26},
pmid = {40146150},
issn = {2164-2591},
mesh = {Humans ; *Image Processing, Computer-Assisted/methods ; *Retinal Diseases/diagnostic imaging ; *Tomography, Optical Coherence ; *Unsupervised Machine Learning ; *Macula Lutea/diagnostic imaging ; *Deep Learning ; },
abstract = {PURPOSE: The purpose of this study was to develop a robust and general purpose artificial intelligence (AI) system that allows the identification of retinal optical coherence tomography (OCT) volumes with pathomorphological manifestations not present in normal eyes in screening programs and large retrospective studies.<br><br>METHODS: An unsupervised anomaly detection deep learning approach for the screening of retinal OCTs with any pathomorphological manifestations via Teacher-Student knowledge distillation is developed. The system is trained with only normal cases without any additional manual labeling. At test time, it scores how anomalous a sample is and produces localized anomaly maps with regions of interest in a B-scan. Fovea-centered OCT scans acquired with Spectralis (Heidelberg Engineering) were considered. A total of 3358 patients were used for development and testing. The detection performance was evaluated in a large data cohort with different pathologies including diabetic macular edema (DME) and the multiple stages of age-related macular degeneration (AMD) and on external public datasets with various disease biomarkers.<br><br>RESULTS: The volume-wise anomaly detection receiver operating characteristic (ROC) area under the curve (AUC) was 0.94 &#xb1; 0.05 in the test set. Pathological B-scan detection on external datasets varied between 0.81 and 0.87 AUC. Qualitatively, the derived anomaly maps pointed toward diagnostically relevant regions. The behavior of the system across the datasets was similar and consistent.<br><br>CONCLUSIONS: Anomaly detection constitutes a valid complement to supervised systems aimed at improving the success of vision preservation and eye care, and is an important step toward more efficient and generalizable screening tools.<br><br>TRANSLATIONAL RELEVANCE: Deep learning approaches can enable an automated and objective screening of a wide range of pathological retinal conditions that deviate from normal appearance.},
}
@article {pmid40146119,
year = {2025},
author = {Christen, WG and Rist, PM and Moorthy, MV and Smith, DC and Holman, B and Clar, A and Glynn, RJ and Mares, JA and Sobrin, L and Shadyab, AH and Allison, MA and Millen, AE and Manson, JE and Sesso, HD and , },
title = {Cocoa Flavanol Supplementation and Risk of Age-Related Macular Degeneration: An Ancillary Study of the COSMOS Randomized Clinical Trial.},
journal = {JAMA ophthalmology},
volume = {143},
number = {5},
pages = {429-437},
pmid = {40146119},
issn = {2168-6173},
mesh = {Humans ; Female ; Aged ; Male ; Double-Blind Method ; *Dietary Supplements ; *Macular Degeneration/prevention &amp; control/epidemiology/diagnosis ; Middle Aged ; *Flavonols/administration &amp; dosage ; Risk Factors ; Aged, 80 and over ; *Cacao ; *Plant Extracts/administration &amp; dosage ; Disease Progression ; Follow-Up Studies ; Incidence ; },
abstract = {IMPORTANCE: Abnormalities of choroidal blood flow in the eye are associated with occurrence of age-related macular degeneration (AMD). Cocoa flavanols show beneficial effects on vascular risk factors in small and short-term trials and may help reduce AMD risk.<br><br>OBJECTIVE: To examine whether daily supplementation with cocoa extract, a source of flavanols, prevents the development or progression of AMD.<br><br>This was a prespecified ancillary study of the COSMOS (COcoa Supplement and Multivitamins Outcomes Study) trial, a double-blind, placebo-controlled, 2&#x2009;&#xd7;&#x2009;2 factorial randomized clinical trial of a cocoa extract supplement and a multivitamin supplement in the prevention of cardiovascular disease and cancer among 21&#x202f;442 US adults, including 12&#x202f;666 women aged 65 years and older and 8776 men aged 60 years and older. The intervention phase was performed from June 2015 through December 2020; data analysis was completed in August 2024.<br><br>INTERVENTION: Cocoa extract supplement (500 mg/day cocoa flavanols, including 80 mg (-)-epicatechin) or placebo.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was a composite of incident cases of AMD plus cases of progression to advanced AMD (geographic atrophy, neovascular membrane, retinal pigment epithelium detachment, or disciform scar) among participants with AMD at baseline, based on self-report confirmed by medical record review.<br><br>RESULTS: Mean (SD) participant age was 72.1 (6.6) years, and 12&#x202f;666 participants (59.1%) were female. During a median (IQR) period of 3.6 (3.2-4.2) years of treatment and follow-up, 344 participants (1.6%) experienced a confirmed AMD event (316 incident AMD, 28 progression to advanced AMD). For the primary composite end point, there were 159 cases (1.5%) in the cocoa extract group and 185 cases (1.7%) in the placebo group (hazard ratio [HR], 0.87; 95% CI, 0.71-1.08; P&#x2009;=&#x2009;.21). Separate Cox models fitted because of evidence of nonproportional hazards (P&#x2009;=&#x2009;.048) indicated a 23% decreased risk in the cocoa extract group during the first 2 years of treatment (HR, 0.77; 95% CI, 0.59-1.01), with no added benefit for treatment beyond 2 years (HR, 1.06; 95% CI, 0.76-1.50). Similar time-dependent findings were observed for the secondary trial outcomes of incident visually significant AMD and advanced AMD.<br><br>CONCLUSIONS AND RELEVANCE: In this ancillary study of the COSMOS randomized clinical trial, cocoa extract supplementation for a median period of 3.6 years among older women and men had no effect overall on occurrence of AMD. However, a possible modest treatment effect early in the trial could not be ruled out, which warrants further investigation to clarify whether cocoa extract may help reduce AMD risk.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03205202.},
}
@article {pmid40145579,
year = {2025},
author = {Zhang, DL and Finn, AP},
title = {Glucagon-like peptide-1 receptor agonists and the eye.},
journal = {Current opinion in ophthalmology},
volume = {36},
number = {5},
pages = {407-413},
pmid = {40145579},
issn = {1531-7021},
mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; *Hypoglycemic Agents/therapeutic use/adverse effects ; *Eye Diseases/drug therapy ; },
abstract = {PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have gained popularity as an antidiabetic and weight loss agent with protective cardiovascular outcomes, but attention to the potential ocular side effects has grown. This review aims to consolidate the existing evidence on the effects of GLP-1RA on conditions such as diabetic retinopathy (DR), nonarteritic ischemic optic neuropathy (NAION), glaucoma, age-related macular degeneration (AMD), idiopathic intracranial hypertension (IIH), and dry eye disease (DED).<br><br>RECENT FINDINGS: The effect of GLP-1RA on DR is controversial but likely linked to rapid correction of hemoglobin A1c levels. GLP-1RA may be associated with increased risk of NAION, although the mechanism remains elusive. Protective effects have been shown against glaucoma, AMD, and DED possibly due to its anti-inflammatory properties, and these medications may decrease intracranial pressure in IIH.<br><br>SUMMARY: As the usage of GLP-1RA increases, further dedicated ocular safety trials are key to determining the risk of eye-related complications. Given the limited prospective evidence available and the proven systemic benefits of the medication, as well as its potential protective effects on certain eye diseases, GLP-1RA use should generally not be discouraged in most patients. Regular ophthalmologic follow up is important in patients considered at higher risk of ocular adverse events.},
}
@article {pmid40143815,
year = {2025},
author = {Yagi, H and Boeck, M and Neilsen, K and Yang, J and Ko, M and Tomita, Y and Negishi, K and Fu, Z and Sun, Y and Smith, LEH},
title = {Choroidal Neovascularization Is Suppressed With Activation of TREM2 in Mononuclear Phagocytes-Brief Report.},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
volume = {45},
number = {5},
pages = {769-777},
pmid = {40143815},
issn = {1524-4636},
support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01 EY017017/EY/NEI NIH HHS/United States ; R01 EY030140/EY/NEI NIH HHS/United States ; U54 HD090255/HD/NICHD NIH HHS/United States ; R01 EY030904/EY/NEI NIH HHS/United States ; R01 EY032492/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Choroidal Neovascularization/metabolism/prevention &amp; control/genetics/pathology ; *Receptors, Immunologic/metabolism/genetics/deficiency/agonists ; Mice, Inbred C57BL ; Disease Models, Animal ; *Membrane Glycoproteins/metabolism/genetics/deficiency/agonists ; Phagocytosis/drug effects ; Mice, Knockout ; Mice ; Signal Transduction ; RAW 264.7 Cells ; Tumor Necrosis Factor-alpha/metabolism ; *Macrophages/metabolism/drug effects ; *Phagocytes/metabolism/drug effects ; Male ; *Choroid/blood supply/pathology/metabolism ; *Macular Degeneration/metabolism/genetics/pathology/prevention &amp; control ; },
abstract = {BACKGROUND: Mononuclear phagocytes contribute to pathological angiogenesis in age-related macular degeneration, a leading worldwide cause of visual impairment. However, the mechanisms that orchestrate the functions of mononuclear phagocytes remain poorly understood. TREM2 (triggering receptor on myeloid cells 2) has been shown to be crucial for the activation of mononuclear phagocytes in atherosclerosis, fatty liver disease, and Alzheimer disease. The objective of this study was to investigate the role of TREM2 in pathological angiogenesis in age-related macular degeneration.<br><br>METHODS: C57BL/6J and Trem2 knockout mice were subjected to laser-induced choroidal neovascularization, a model of choroidal neovascular age-related macular degeneration. Purified bovine sulfatide and agonist anti-TREM2 antibody was used to activate TREM2 signaling. The expression of TREM2 or downstream signals were assessed with immunohistochemistry or real-time quantitative PCR. In vitro murine macrophage RAW264.7 cells were used to investigate the direct impact of sulfatide on inflammatory and phagocytic responses.<br><br>RESULTS: We found that pharmacological activation of TREM2 suppressed laser-induced choroidal neovessel formation. The activation of TREM2 in mononuclear phagocytes suppressed TNF (tumor necrosis factor) and subsequently promoted phagocytosis.<br><br>CONCLUSIONS: These findings demonstrate that activation of TREM2 in mononuclear phagocytes suppresses the proinflammatory response, promotes phagocytosis, and impedes choroidal neovessel formation. Our study provides insight into the critical role of TREM2 in pathological angiogenesis.},
}
@article {pmid40143214,
year = {2025},
author = {Hosoda, S and Sakurada, Y and Fukuda, Y and Kotoda, Y and Kikushima, W and Kashiwagi, K},
title = {Short-Term Outcomes of Three Consecutive Monthly Loading Administrations of Aflibercept 8 Mg for Treatment-Naïve Exudative Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {3},
pages = {},
pmid = {40143214},
issn = {1424-8247},
abstract = {Background/Objectives: The aim was to investigate the short-term outcomes of three consecutive monthly aflibercept 8 mg administrations for treatment-naïve eyes with exudative age-related macular degeneration (AMD). Methods: Twenty-one eyes with exudative AMD were included (type 1 macular neovascularization: eleven eyes; type 2 macular neovascularization, four eyes; and polypoidal choroidal vasculopathy (PCV), six eyes). All eyes received three consecutive monthly administrations of aflibercept 8 mg (114.3 mg/mL) at an injection volume of 0.07 mL. Indocyanine green angiography (ICGA) was performed on eyes with PCV at baseline and at the 3-month visit. Results: The best-corrected visual acuity significantly (BCVA) improved from 0.31 ± 0.38 (baseline) to 0.25 ± 0.38 at the 3-month visits (p = 0.035). Dry macula achieved 62% and 100% at the 1-month and 3-month visits, respectively. Central retinal thickness and subfoveal choroidal thickness significantly decreased by 55.7% and 19.8%, from 341 ± 112 (baseline) to 190 ± 64 (3-month visits) and from 192 ± 50 (baseline) to 154 ± 51 (3-month visits), respectively (both p < 0.001). Complete regression of polypoidal lesions was seen in five (83.3%) eyes out of six on ICGA at the 3-month visit. No systemic adverse events were noted, and one eye developed a retinal pigment epithelial tear one month after the first injection. Conclusions: Three consecutive monthly administrations of aflibercept (8 mg) were safe and effective for resolving exudation and polyp regression, with significant BCVA improvement in treatment-naïve eyes with exudative AMD.},
}
@article {pmid40143179,
year = {2025},
author = {Shanaida, M and Mykhailenko, O and Lysiuk, R and Hudz, N and Balwierz, R and Shulhai, A and Shapovalova, N and Shanaida, V and Bjørklund, G},
title = {Carotenoids for Antiaging: Nutraceutical, Pharmaceutical, and Cosmeceutical Applications.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {3},
pages = {},
pmid = {40143179},
issn = {1424-8247},
abstract = {Background: Carotenoids are bioactive tetraterpenoid C40 pigments that are actively synthesized by plants, bacteria, and fungi. Compounds such as α-carotene, β-carotene, lycopene, lutein, astaxanthin, β-cryptoxanthin, fucoxanthin, and zeaxanthin have attracted increasing attention for their antiaging properties. They exhibit antioxidant, neuroprotective, and anti-inflammatory properties, contributing to the prevention and treatment of age-related diseases. Objectives: The aim of this study was to comprehensively analyze the pharmacological potential and biological mechanisms of carotenoids associated with age-related disorders and to evaluate their application in nutraceuticals, pharmaceuticals, and cosmeceuticals. Methods: A systematic review of studies published over the past two decades was conducted using the databases PubMed, Scopus, and Web of Science. The selection criteria included clinical, in silico, in vivo, and in vitro studies investigating the pharmacological and therapeutic effects of carotenoids. Results: Carotenoids demonstrate a variety of health benefits, including the prevention of age-related macular degeneration, cancer, cognitive decline, metabolic disorders, and skin aging. Their role in nutraceuticals is well supported by their ability to modulate oxidative stress and inflammatory pathways. In pharmaceuticals, carotenoids show promising results in formulations targeting neurodegenerative diseases and metabolic disorders. In cosmeceuticals, they improve skin health by protecting it against UV radiation and oxidative damage. However, bioavailability, optimal dosages, toxicity, and interactions with other bioactive compounds remain critical factors to maximize therapeutic efficacy and still require careful evaluation by scientists. Conclusions: Carotenoids are promising bioactive compounds for antiaging interventions with potential applications in a variety of fields. Further research is needed to optimize their formulas, improve bioavailability, and confirm their long-term safety and effectiveness, especially in the aging population.},
}
@article {pmid40143063,
year = {2025},
author = {Enzendorfer, ML and Tratnig-Frankl, M and Eidenberger, A and Schrittwieser, J and Kuchernig, L and Schmidt-Erfurth, U},
title = {Rethinking Clinical Trials in Age-Related Macular Degeneration: How AI-Based OCT Analysis Can Support Successful Outcomes.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {3},
pages = {},
pmid = {40143063},
issn = {1424-8247},
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. Due to an aging population, its prevalence is expected to increase, making novel and optimized therapy options imperative. However, both late-stage forms of the disease, neovascular AMD (nAMD) and geographic atrophy (GA), exhibit considerable variability in disease progression and treatment response, complicating the evaluation of therapeutic efficacy and making it difficult to design clinical trials that are both inclusive and statistically robust. Traditional trial designs frequently rely on generalized endpoints that may not fully capture the nuanced benefits of treatment, particularly in diseases like GA, where functional improvements can be gradual or subtle. Artificial intelligence (AI) has the potential to address these issues by identifying novel, condition-specific biomarkers or endpoints, enabling precise patient stratification and improving recruitment strategies. By providing an overview of the advances and application of AI-based optical coherence tomography analysis in the context of AMD clinical trials, this review highlights the transformative potential of AI in optimizing clinical trial outcomes for patients with nAMD or GA secondary to AMD.},
}
@article {pmid40143057,
year = {2025},
author = {Bege, M and Ghanem Kattoub, R and Borbás, A},
title = {The 20th Anniversary of Pegaptanib (MacugenTM), the First Approved Aptamer Medicine: History, Recent Advances and Future Prospects of Aptamers in Therapy.},
journal = {Pharmaceutics},
volume = {17},
number = {3},
pages = {},
pmid = {40143057},
issn = {1999-4923},
support = {DETKA 2024//University of Debrecen Scientific Research Bridging Fund/ ; },
abstract = {In addition to classic small-molecule drugs and modern protein-based biologics, an intriguing class of medicines is the therapeutic oligonucleotides. Most approved drugs in this category are antisense oligomers or those acting via RNA interference, both of which use base hybridization. Aptamers, also known as chemical antibodies form a smaller, yet equally interesting group of oligonucleotides that can recognize a wide range of molecular targets. Despite their high potential, only two aptamers have been approved to date, pegaptanib (MacugenTM) and avacincaptad pegol (IzervayTM), both for the treatment of age-related macular degeneration (AMD). Targeting vascular endothelial growth factor (VEGF), which plays an important role in the pathogenesis of many eye diseases, pegaptanib emerged as the first anti-VEGF agent and was used in various indications, further inspiring the development of other anti-VEGF therapies. In this review, we summarize the history of the first approved aptamer medicine, pegaptanib. We describe its chemistry and track its development from the earliest stages to the preclinical phase, clinical trials, and eventual regulatory approval. Additionally, we evaluate its position among other therapeutic agents and provide a comprehensive overview of pegaptanib's efficacy, safety, and cost-effectiveness, comparing these aspects with those of monoclonal antibodies with similar indications, bevacizumab and ranibizumab.},
}
@article {pmid40142610,
year = {2025},
author = {Imazeki, M and Takeuchi, M and Yasukawa, T and Terasaki, H and Yamamoto, Y and Jujo, T and Wakuta, M and Matsubara, H and Mitamura, Y and Kato, A and Kondo, M and Kimura, K and Takagi, H and Gomi, F and Sakamoto, T and , },
title = {Predictors of Disengagement and Loss to Follow-Up of Intravitreal Injection for Neovascular Age-Related Macular Degeneration in a Real-World Clinical Setting: Post Hoc Analysis of the Multicenter Survey from the Japanese Clinical Retinal Study (J-CREST) Group.},
journal = {Journal of clinical medicine},
volume = {14},
number = {6},
pages = {},
pmid = {40142610},
issn = {2077-0383},
abstract = {Background/Objectives: In a recent study, we investigated anti-VEGF treatment strategies for three subtypes of neovascular age-related macular degeneration (nAMD)-typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)-among a large cohort of Japanese patients. To further explore these findings, we conducted a post hoc analysis of this cohort to identify factors associated with the discontinuation of anti-VEGF therapy for nAMD in a real-world clinical setting. Methods: We collected medical records of patients newly diagnosed with nAMD who initiated intravitreal anti-VEGF antibody injection therapy. Patients were divided into two groups: those who continued anti-VEGF therapy for one year and those who discontinued treatment. Baseline best-corrected visual acuity, optical coherence tomography (OCT) findings, injection regimen, and the type of anti-VEGF antibody drug used were analyzed using univariate and multivariate analyses. Results: A total of 667 treatment-naïve nAMD patients initiated anti-VEGF agents and followed the therapy for 1 year. The one-year dropout rate in this study was 13%. Logistic regression analysis revealed that poor initial visual acuity and a PRN treatment regimen were significantly associated with higher odds of dropout. Age, gender, systemic factors, and the choice of intravitreal injection did not show any significant differences. Conclusions: Poor initial visual acuity and PRN treatment regimens may increase the risk of treatment dropout and should be carefully monitored.},
}
@article {pmid40142244,
year = {2025},
author = {Olawade, DB and Weerasinghe, K and Mathugamage, MDDE and Odetayo, A and Aderinto, N and Teke, J and Boussios, S},
title = {Enhancing Ophthalmic Diagnosis and Treatment with Artificial Intelligence.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {3},
pages = {},
pmid = {40142244},
issn = {1648-9144},
mesh = {Humans ; *Artificial Intelligence/trends ; *Ophthalmology/methods/trends ; *Eye Diseases/diagnosis/therapy ; Deep Learning ; },
abstract = {The integration of artificial intelligence (AI) in ophthalmology is transforming the field, offering new opportunities to enhance diagnostic accuracy, personalize treatment plans, and improve service delivery. This review provides a comprehensive overview of the current applications and future potential of AI in ophthalmology. AI algorithms, particularly those utilizing machine learning (ML) and deep learning (DL), have demonstrated remarkable success in diagnosing conditions such as diabetic retinopathy (DR), age-related macular degeneration, and glaucoma with precision comparable to, or exceeding, human experts. Furthermore, AI is being utilized to develop personalized treatment plans by analyzing large datasets to predict individual responses to therapies, thus optimizing patient outcomes and reducing healthcare costs. In surgical applications, AI-driven tools are enhancing the precision of procedures like cataract surgery, contributing to better recovery times and reduced complications. Additionally, AI-powered teleophthalmology services are expanding access to eye care in underserved and remote areas, addressing global disparities in healthcare availability. Despite these advancements, challenges remain, particularly concerning data privacy, security, and algorithmic bias. Ensuring robust data governance and ethical practices is crucial for the continued success of AI integration in ophthalmology. In conclusion, future research should focus on developing sophisticated AI models capable of handling multimodal data, including genetic information and patient histories, to provide deeper insights into disease mechanisms and treatment responses. Also, collaborative efforts among governments, non-governmental organizations (NGOs), and technology companies are essential to deploy AI solutions effectively, especially in low-resource settings.},
}
@article {pmid40142183,
year = {2025},
author = {Asakage, M and Noma, H and Yasuda, K and Goto, H and Shimura, M},
title = {Dynamics of Inflammatory Factors in Aqueous Humor During Brolucizumab Treatment for Age-Related Macular Degenerations: A Case Series.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {3},
pages = {},
pmid = {40142183},
issn = {1648-9144},
support = {22K09821//JSPS KAKENHI/ ; },
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use/adverse effects ; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects ; *Aqueous Humor/chemistry/metabolism/drug effects ; Inflammation ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/analysis ; },
abstract = {Anti-vascular endothelial growth factor (VEGF) treatment with intravitreal brolucizumab (IVBr) was launched as a novel treatment for neovascular age-related macular degeneration (AMD), but the incidence of intraocular inflammation (IOI) as a specific adverse effect of brolucizumab has been reported. We evaluated the dynamics of inflammatory factors in AMD in patients with or without IOI before and after anti-VEGF treatment with IVBr. We describe three patients who did not develop inflammation after three consecutive administrations of IVBr and three in whom inflammation occurred after the first IVBr treatment. The presence or absence of inflammation was determined by slit-lamp examination and a laser flare meter. Aqueous humor was obtained during anti-VEGF treatment with IVBr. Levels of VEGF, platelet-derived growth factor (PDGF)-AA, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, interferon-inducible 10 kDa protein (IP-10), Fms-related tyrosine kinase 3 ligands (Flt-3L), and fractalkine were measured. Vision worsened in one patient who developed IOI after initial IVBr, so IVBr was discontinued and the patient was switched to intravitreal aflibercept with sub-tenon injection of triamcinolone acetonide. IVBr was continued in the two other patients with IOI. VEGF decreased after IVBr in all patients with and without IOI. On the other hand, at 1 month IL-6, IL-8, MCP-1, IP-10, and Flt-3L were higher in the three patients with IOI compared with baseline and with the three patients without IOI. In two patients with IOI, not only flares but also IL-8, IP-10, and Flt-3L decreased from 1 to 2 months after IVBr despite continued IVBr. This case series might lead to a better understanding of the pathogenesis of IOI after IVBr.},
}
@article {pmid40141285,
year = {2025},
author = {Ueki, S and Suzuki, Y},
title = {New Perspective on Aqueous Humor Circulation: Retina Takes the Lead.},
journal = {International journal of molecular sciences},
volume = {26},
number = {6},
pages = {},
pmid = {40141285},
issn = {1422-0067},
mesh = {Humans ; *Aqueous Humor/metabolism/physiology ; *Retina/metabolism/physiology ; Animals ; Glymphatic System/metabolism/physiology ; Aquaporin 4/metabolism ; Ependymoglial Cells/metabolism ; Vitreous Body/metabolism ; },
abstract = {Ocular aqueous humor plays an important role in maintaining retinal function. Recent findings indicate that aqueous humor, which flows into the vitreous body, is probably absorbed by Müller cells in the retina, and this process is mediated by aquaporin-4. In this review, we aim to summarize the results of studies on classical aqueous humor circulation and postiridial flow, a pathway proposed in the late 1980s for the inflow of aqueous humor into the vitreous body. In addition, we aim to discuss the retinal glymphatic pathway, inferred by recent findings, with a focus on the anatomical location of aquaporins and barriers that regulate water movement within the tissue. Similarly to the cerebral glymphatic flow, the function of the retinal glymphatic pathway may decline with age, as supported by our findings. In this review, we also discuss age-related ocular diseases that might be associated with the dysfunction of the retinal glymphatic pathway.},
}
@article {pmid40141114,
year = {2025},
author = {Ciurariu, E and Tirziu, AT and Varga, NI and Hirtie, B and Alexandru, A and Ivan, CS and Nicolescu, L},
title = {Short-Chain Fatty Acids and the Gut-Retina Connection: A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {26},
number = {6},
pages = {},
pmid = {40141114},
issn = {1422-0067},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fatty Acids, Volatile/metabolism ; Animals ; *Retina/metabolism ; Macular Degeneration/metabolism ; Diabetic Retinopathy/metabolism/microbiology ; *Retinal Diseases/metabolism/microbiology ; },
abstract = {The interplay between gut microbiota and retinal health, known as the gut--retina axis, has gained increasing attention in recent years. Short-chain fatty acids (SCFAs), metabolites produced by gut microbiota, have been identified as key mediators of gut-retina communication. This systematic review explores the role of SCFAs in retinal health and their potential impact on the development and progression of retinal diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. A literature search was conducted across multiple databases, including PubMed, Google Scholar, and Science Direct, to identify studies published between 2014 and December 2024. Studies were included if they investigated the effects of SCFAs on retinal structure, function, or disease pathogenesis in animal models or human subjects. The review included 10 original articles spanning both preclinical and clinical studies. Evidence suggests that SCFAs play a crucial role in maintaining retinal homeostasis through anti-inflammatory and neuroprotective mechanisms. Dysbiosis of the gut microbiota, leading to altered SCFA production, was associated with increased retinal inflammation, oxidative stress, and vascular dysfunction. Furthermore, reduced SCFA levels were linked to the progression of retinal diseases, such as diabetic retinopathy and age-related macular degeneration. Modulation of gut microbiota and SCFA levels through dietary interventions or probiotics may represent a novel therapeutic strategy for preventing or managing retinal diseases. Further research is needed to elucidate the precise molecular mechanisms underlying SCFA-mediated retinal protection and to evaluate the efficacy of targeted therapies in clinical settings.},
}
@article {pmid40140856,
year = {2025},
author = {Wang, X and Jiang, H and Zhang, C},
title = {Association of systemic inflammatory biomarkers with ocular disease: a large population-based cross-sectional study.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {206},
pmid = {40140856},
issn = {2047-783X},
mesh = {Humans ; Cross-Sectional Studies ; *Biomarkers/blood ; Female ; Male ; Middle Aged ; *Eye Diseases/epidemiology/blood ; *Inflammation/blood/epidemiology ; Aged ; Adult ; United States/epidemiology ; Prevalence ; Nutrition Surveys ; },
abstract = {BACKGROUND: The aim of this study was to explore the association of systemic inflammatory biomarkers (systemic immune-inflammation (SII) index and systemic inflammatory response index (SIRI)) with the prevalence of ocular disease in the general population of the United States (U.S.).<br><br>METHODS: We conducted a cross-sectional study of subjects in the National Health and Nutrition Examination Survey 2005-2008&#xa0;years. For the analysis of the association of SII index, and SIRI with the prevalence of ocular disease (glaucoma, cataract, age-related macular degeneration (ARMD), and diabetic retinopathy), the restricted cubic spline (RCS) plot, multivariable logistic regression models, and subgroup analysis were performed.<br><br>RESULTS: There was a total of 5377 individuals. As shown by the RCS plot, SII index and SIRI were linked with ARMD risk in a U-shaped pattern. Additionally, the SII index and SIRI were linearly positive with glaucoma and cataract. Finally, the risk of diabetic retinopathy was associated with the L-shaped and N-shaped curves of the SII index and SIRI, respectively.<br><br>CONCLUSIONS: Two new systemic inflammatory biomarkers, SII index and SIRI, are closely related to the risk of eye disease. There are different associations between SII index and different ocular diseases. This should raise more concerns and lead to better prevention strategies for systemic inflammation.},
}
@article {pmid40139686,
year = {2025},
author = {Adhikari, P and Zele, AJ and Feigl, B},
title = {Rapid clinical assessment of spatial contrast sensitivity changes in retinal disease and ageing.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {9},
pages = {1088-1090},
doi = {10.1136/bjo-2024-326490},
pmid = {40139686},
issn = {1468-2079},
mesh = {Humans ; *Contrast Sensitivity/physiology ; Aged ; Middle Aged ; Aged, 80 and over ; Male ; Female ; *Aging/physiology ; Adult ; Visual Acuity/physiology ; *Vision Tests/instrumentation/methods ; Young Adult ; *Retinal Diseases/physiopathology/diagnosis ; Reproducibility of Results ; *Vision Disorders/physiopathology/diagnosis ; },
abstract = {Evidence suggests best-corrected visual acuity is not sensitive to subtle vision losses in early disease stages, indicating the need for other tests. Here, we quantified contrast sensitivity in 99 people (20-88 years): 52 with eye diseases (10 with early AMD, 9 diabetics without retinopathy, 22 glaucoma suspects, 11 high myopes) and 47 age-matched healthy controls using a new spatial vision chart (0.28-100% Weber contrasts; 3-60 c/° frequencies). In retinal diseases and healthy ageing, the chart detected frequency-dependent losses; sensitivity was reduced at 3 and 8 c/° in AMD, at 6 and 8 c/° in diabetes, and at all frequencies in myopia and with ageing. Intrasession repeatability was excellent and spatial contrast changes were in accordance with deficits identified previously using complex and time-consuming psychophysical tests. The chart offers a simple, rapid and readily available tool for clinical use to document early visual deficits.},
}
@article {pmid40139459,
year = {2025},
author = {Grimaldi, G and Ambresin, A and Pfister, IB and Schild, C and Plasencia, C and Hatz, K and Stillenmunkes, R and Munk, MR and Paris, A and Menghini, M and Artemiev, D and Ebneter, A and Cattaneo, J and de Oliveira Figueiredo, EC and Eandi, CM and Fröhlich, J and Feltgen, N and Spitznagel, T and Somfai, GM and Cozzi, M and Zweifel, S and Weinberger, A and Garweg, JG},
title = {One-Year Outcomes after Switching to Faricimab in Eyes with Pretreated Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {9},
pages = {838-847},
doi = {10.1016/j.oret.2025.03.015},
pmid = {40139459},
issn = {2468-6530},
mesh = {Humans ; Retrospective Studies ; *Visual Acuity ; Male ; Female ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Aged ; *Drug Substitution ; Treatment Outcome ; Fluorescein Angiography/methods ; Time Factors ; Switzerland ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To report the efficacy and safety of switching to faricimab in a real-world, Swiss cohort of patients with pretreated neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, multicenter, longitudinal observational study conducted at 11 centers of the Swiss Retina Research Network.<br><br>SUBJECTS: We included 353 eyes of 325 patients who were switched to intravitreal faricimab after prior anti-VEGF therapy and followed for a minimum of 12 months between May 1, 2022, and October 30, 2024.<br><br>METHODS: Demographic characteristics, baseline functional and OCT findings, treatment history, and outcomes at 12 months after switch to faricimab were extracted from the patients' electronic case report forms.<br><br>MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) and pigment epithelial detachment, treatment intervals, and safety signals.<br><br>RESULTS: Twelve months after switch, mean BCVA remained unchanged, whereas mean CST decreased from 315.3 to 263.9 &#x3bc;m (P < 0.01). Fast drying (absence of RF) after 1 faricimab injection was observed in 134 eyes (38%) and correlated positively with the treatment interval at 12 months (r(301) = 0.24; P < 0.01). After 12 months, 169 (47.9%) eyes demonstrated the absence of RF compared with 10.2% at switch. Mean treatment interval increased from 5.8 &#xb1; 2.5 weeks at switch to 8.3 &#xb1; 4.2 weeks at 12 months, and extended treatment intervals (&#x2265;12 week) were achieved in 20% of patients. Mild intraocular inflammation was reported in 1.7% of cases.<br><br>CONCLUSIONS: Switching to faricimab in pretreated nAMD led to sustained anatomic improvements and stabilization of BCVA, with a substantial reduction in RF compared with baseline. Our results suggest the potential benefits of this switching strategy based on real-world data.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40138234,
year = {2025},
author = {Kim, GH and Bak, S and Kim, HH and Shin, JG and Eom, TJ and Kim, CS and Lee, H},
title = {Phase-Locked Time-Stretch Optical Coherence Tomography for Contrast-Enhanced Retinal Microangiography.},
journal = {IEEE transactions on medical imaging},
volume = {44},
number = {7},
pages = {2906-2920},
doi = {10.1109/TMI.2025.3555112},
pmid = {40138234},
issn = {1558-254X},
mesh = {*Tomography, Optical Coherence/methods/instrumentation ; Humans ; *Retinal Vessels/diagnostic imaging ; *Angiography/methods ; *Retina/diagnostic imaging ; },
abstract = {Optical coherence tomography angiography has transformed retinal vascular imaging by providing non-invasive, high-resolution visualization. However, achieving an optimal balance between field of view, resolution, and three-dimensional microvasculature contrast, particularly in deeper retinal layers, remains challenging. A phase-locked time-stretch optical coherence tomography microangiography system is developed to address these limitations with a 5-MHz A-line rate and sub-nm phase sensitivity. Utilizing a dual chirped fiber Bragg grating architecture, the swept-source laser achieves an extended coherence length of ~10 mm and a 102-nm bandwidth. A time-stretch analog-to-digital converter overcomes the limitations of conventional multi-MHz optical coherence tomography systems, ensuring a 2-mm imaging depth in the air with high spatial resolution. The proposed system enables high-contrast, depth-encoded mapping of key retinal structures, including the superficial and deep capillary plexuses and the choriocapillaris. Compared to a state-of-the-art system, the proposed approach demonstrates enhanced resolution, improved contrast, and faster imaging speeds, enhancing its potential for diagnosing and monitoring retinal and systemic diseases like age-related macular degeneration, diabetic retinopathy, and Alzheimer's disease.},
}
@article {pmid40137928,
year = {2025},
author = {Saigal, K and Salama, JE and Pardo, AA and Lopez, SE and Gregori, NZ},
title = {Modifiable Lifestyle Risk Factors and Strategies for Slowing the Progression of Age-Related Macular Degeneration.},
journal = {Vision (Basel, Switzerland)},
volume = {9},
number = {1},
pages = {},
pmid = {40137928},
issn = {2411-5150},
abstract = {Age-related macular degeneration (AMD) is a multifactorial disorder influenced by genetic, lifestyle, nutritional, and systemic health factors that contribute to increased oxidative stress and chronic inflammation in the retina. This article reviews the recent literature on modifiable lifestyle risk factors for the development and progression of AMD. Smoking (current and former), physical inactivity, prolonged sunlight exposure, as well as conditions such as diabetes, hypertension, cardiovascular disease, and obesity have all been associated with an increased risk of early AMD and its progression. The Age-Related Eye Disease Studies (AREDS and AREDS2) have shown that a specific combination of vitamins E and C, zinc, copper, lutein, and zeaxanthin can significantly reduce the risk of AMD progressing from dry to wet form. Additionally, adherence to a Mediterranean diet, rich in vegetables, fruits, legumes, whole grains, and nuts, has been linked to a lower risk of both early and late AMD. Emerging evidence suggests that these benefits may be influenced by the gut microbiota, as well as genetic and epigenetic factors. Further research into the interactions between these risk factors could pave the way for targeted therapies aimed at preventing or slowing AMD progression.},
}
@article {pmid40137287,
year = {2025},
author = {Dörschmann, P and Kopplin, G and Thalenhorst, T and Seeba, C and Ullah, SF and Srivastava, V and Roider, J and Klettner, A},
title = {Influence of a Very High-Molecular Weight Fucoidan from Laminaria hyperborea on Age-Related Macular Degeneration-Relevant Pathomechanisms in Ocular Cell Models.},
journal = {Marine drugs},
volume = {23},
number = {3},
pages = {},
pmid = {40137287},
issn = {1660-3397},
support = {01/20//Helmut-Ecker foundation/ ; NFR: 310167//Research Council of Norway (Fucomed project)/ ; },
mesh = {*Polysaccharides/pharmacology/chemistry/isolation &amp; purification ; Humans ; Animals ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Laminaria/chemistry ; Retinal Pigment Epithelium/drug effects/metabolism ; Oxidative Stress/drug effects ; Swine ; Cell Survival/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Molecular Weight ; Cell Line, Tumor ; Cell Line ; Interleukin-8/metabolism ; Seaweed ; },
abstract = {Fucoidans from Laminaria hyperborea (LH) can be antioxidative, antiangiogenic, and anti-inflammatory. In this study, a very high-molecular weight (3700 kDa) fucoidan from LH, FucBB04, was tested regarding its bioactivity in age-related macular degeneration (AMD) models in vitro. Primary retinal pigment epithelium (RPE) from pig eyes, human uveal melanoma cell line OMM-1, and RPE cell line ARPE-19 were used. Substituents of the extract were determined with chemical analysis. Cell viability was tested with tetrazolium assay (MTT), oxidative stress was induced by H2O2 or erastin, respectively. Secreted vascular endothelial growth factor A (VEGF-A) was assessed with ELISA. Retinal pigment epithelium 65 kDa protein (RPE65) and protectin (CD59) protein expression were tested in Western blot. Cell barrier was assessed by measuring trans-epithelial electrical resistance (TEER), phagocytic ability by a fluorescence assay. Gene expression and secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) were tested in real-time PCR and ELISA. FucBB04 displayed no oxidative stress protective effects. Its effect on VEGF was inconsistent, with VEGF secretion reduced in primary RPE, but not in ARPE-19. On the other hand, Lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC)-induced IL-6 or IL-8 secretion was reduced by FucBB04, while complement inhibiting protein CD59 was not affected. In addition, FucBB04 did not influence the gene expression of IL-6 or IL-8. Visual cycle protein RPE65 expression, phagocytic ability, and barrier function were reduced by FucBB04. Very high-molecular weight fucoidan from LH shows bioactivities against AMD-related pathological pathways, but adverse effects on RPE function may limit its suitability as a therapeutic compound. Smaller high-molecular weight fucoidans are recommended for further research.},
}
@article {pmid40134779,
year = {2025},
author = {Arslan, U and Arslan, D and Özmert, E},
title = {Electromagnetic Iontophoresis: A Novel Nonsurgical Method for the Treatment of Dense Vitreous and Retinal Hemorrhages.},
journal = {Case reports in ophthalmology},
volume = {16},
number = {1},
pages = {221-231},
pmid = {40134779},
issn = {1663-2699},
abstract = {INTRODUCTION: Vitreous, retinal, and suprochoroidal hemorrhages might develop secondary to trauma, retinal tear or detachment, neovascularization due to ischemic retina. If the clearance of retinal and vitreous hemorrhages can be accelerated, more effective treatments can be planned for the underlying pathology.<br><br>CASE PRESENTATIONS: We present 6 different cases with dense vitreous, preretinal, and subretinal hemorrhages due to Valsalva retinopathy, polypoid choroidal vasculopathy, diabetic retinopathy, neovascular age-related macular degeneration, retinitis pigmentosa with vasculitis, and myopic choroidal neovascularization. To accelerate the clearance of these dense intraocular hemorrhages, a novel nonsurgical method of electromagnetic iontophoresis (MagnoVision&#x2122;) was used together with some appropriate medications in an outpatient setting without any complications or side effects. In all cases, liquefaction of the intraocular hemorrhage began by 5 days and mostly resolved by 10 days. This nonsurgical rapid clearance allowed us to diagnose and evaluate the underlying retinal and choroidal pathologies earlier and to treat them appropriately as early as possible.<br><br>CONCLUSION: Combined use of electromagnetic iontophoresis, subtenon platelet-rich plasma and bevacizumab injection, and oral bromelain can be considered as an effective and safe new treatment method for vitreous and retinal hemorrhages without any need for surgical intervention.},
}
@article {pmid40134284,
year = {2025},
author = {Jones, N and Gore, C and Saedon, H and O'Donnell, C and Mahmood, S},
title = {Efficacy of treatment with faricimab for patients with refractory nAMD.},
journal = {European journal of ophthalmology},
volume = {35},
number = {5},
pages = {1695-1702},
doi = {10.1177/11206721251328097},
pmid = {40134284},
issn = {1724-6016},
mesh = {Humans ; Retrospective Studies ; Visual Acuity/physiology ; Tomography, Optical Coherence ; Male ; Female ; Intravitreal Injections ; Aged ; Treatment Outcome ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged, 80 and over ; Fluorescein Angiography ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Fovea Centralis/pathology ; Antibodies, Bispecific ; },
abstract = {ObjectiveTo investigate the efficacy of treatment with faricimab in patients with refractory neovascular age-related macular degeneration (nAMD).MethodsA Single-centre, retrospective cohort study was conducted on patients treated with faricimab for refractory nAMD. Outcome measures comprised best measured visual acuity (BMVA), central foveal thickness (CFT) on optical coherence tomography (OCT) and mean treatment interval for patients receiving six or more faricimab injections.ResultsCFT was shown to significantly decrease for all eyes (N = 52) treated with six faricimab injections (χ 52.88 df 5 p < 0.001) from baseline (274 ± 73 µm) and subsequent injections (244 ± 59 µm). BMVA remained stable (χ 6.45 df 5 p = 0.26) from baseline treatment (baseline, 67 letters ± 13) and subsequent injections with faricimab (67 letters ± 14, injection 6). Mean treatment interval with faricimab increased from 4.2 weeks to 5.8 weeks indicating sustained results. Zero cases of post-operative complications were reported.ConclusionThis study adds to the growing body of real-world evidence supporting the efficacy of faricimab in treating refractory nAMD. With improvements in anatomical outcomes and an extended treatment interval, whilst maintaining stable vision, faricimab emerges as a promising therapeutic option for patients with refractory nAMD.},
}
@article {pmid40133689,
year = {2025},
author = {Hafner, M and Asani, B and Eckardt, F and Siedlecki, J and Schworm, B and Priglinger, SG and Schiefelbein, J},
title = {Deep-Learning-Assisted Analysis of Early Biomarker Changes in Treatment-Naïve Patients with Neovascular AMD Under Intravitreal Faricimab.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {5},
pages = {1025-1037},
pmid = {40133689},
issn = {2193-8245},
support = {031L0210A//Bundesministerium f&#xfc;r Bildung und Forschung/ ; ZT-I-PF-5-01//Helmholtz Association/ ; },
abstract = {INTRODUCTION: Artificial intelligence (AI)-driven biomarker segmentation offers an objective approach to assessing neovascular age-related macular degeneration (nAMD). In addition, faricimab, a bispecific VEGF and Ang-2 inhibitor, presents new potential in disease management. This study applies an AI-based segmentation algorithm to quantify key optical coherence tomography (OCT) biomarkers and assess the short-term efficacy of intravitreal faricimab in treatment-naïve patients.<br><br>METHODS: This retrospective analysis includes 40 eyes from 38 treatment-na&#xef;ve patients with nAMD treated with faricimab at LMU University Hospital Munich between January 2023 and September 2024. Patients received 4-monthly intravitreal injections. Biomarkers of disease activity, including central retinal thickness (CRT), intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM) and fibrovascular pigment epithelium detachment (fvPED), were quantified using a deep learning-based semantic segmentation algorithm. Best-corrected visual acuity (BCVA) and OCT imaging data were analyzed at baseline (mo0) and after 1 (mo1), 2 (mo2) and 3 months (mo3).<br><br>RESULTS: AI-driven analysis revealed significant reductions in key biomarkers. CRT decreased from 433.6 (IQR: 306.6) &#xb5;m at mo0 to 241.5 (IQR: 130.8) &#xb5;m at mo3 (p&#x2009;<&#x2009;0.0001). IRF and SRF volumes were reduced by > 99% from mo0 to mo3 (both p&#x2009;<&#x2009;0.0001). BCVA improved from 0.60 (IQR: 0.30) logMAR at mo0 to 0.40 (IQR: 0.33) logMAR at mo3 (p&#x2009;<&#x2009;0.0001). Correlation analysis identified IRF and SHRM reductions as the strongest predictors of visual improvement.<br><br>CONCLUSION: This study demonstrates the potential of AI-assisted biomarker analysis for precise disease monitoring in nAMD. Faricimab significantly reduced disease activity biomarkers and improved visual acuity in treatment-na&#xef;ve patients, reinforcing its efficacy in early disease control. Future studies should explore long-term outcomes and further integrate AI-driven biomarker evaluation in clinical practice.},
}
@article {pmid40132899,
year = {2025},
author = {Moore, N and Cushley, L and Wright, D and McCann, R and Moutray, T and Peto, T and Azuara-Blanco, A and Jackson, J},
title = {Associations between certification of visual impairment and socioeconomic deprivation: a study using data from the regional Northern Ireland sight impairment certification database.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40132899},
issn = {2397-3269},
mesh = {Humans ; Northern Ireland/epidemiology ; Female ; Male ; Aged ; Middle Aged ; *Visual Acuity ; Databases, Factual ; *Certification ; Aged, 80 and over ; *Persons with Visual Disabilities/statistics &amp; numerical data ; *Social Deprivation ; *Vision, Low/epidemiology ; Adult ; *Vision Disorders/epidemiology ; Retrospective Studies ; },
abstract = {BACKGROUND/AIMS: Within the UK, there are approximately 340 000 people who are registered as sight impaired (SI) or severely Sight Impaired (SSI), mainly due to age-related macular degeneration (AMD), diabetic eye disease (DED) and glaucoma. This study aimed to explore the association between certification of visual impairment (CVI) and socioeconomic deprivation.<br><br>METHODS: Data from all CVI forms across Northern Ireland (NI) between 2018 to 2022 were used for analysis. Data collected included age, sex, visual acuity (logMAR), postcode and certification category. Deprivation measure was obtained using the Northern Ireland Multiple Deprivation Measure 2017 (NIMDM17). Patients were allocated a quintile from 1 (most deprived) to 5 (least deprived).<br><br>RESULTS: Of the 1863 patients with VI who met the inclusion criteria, 1798 (97%) had postal codes recorded and therefore were allocated an NIMDM17 score. There were 755 patients in total, which were grouped into the most deprived and least deprived areas (357 and 398, respectively). Results showed that patients living in more deprived areas were significantly more likely to be certified as SI/SSI at a younger age than those living in less deprived areas (80.97 vs 85.77, respectively, p<0.001). This was seen in patients with AMD (85.1 vs 87.5, p=0.005) and DED (63.9 vs 69.8, p=0.013) but not in glaucoma (80.9 vs 84.1, p=0.073).<br><br>CONCLUSION: This study has shown that patients living in more deprived areas are more likely to be certified as SI or SSI at a significantly younger age compared with patients from less deprived areas across the certification database.},
}
@article {pmid40131702,
year = {2025},
author = {Wu, KY and Osman, RM and Esomchukwu, O and Marchand, M and Nguyen, BH and Tran, SD},
title = {Advances in Regenerative Medicine, Cell Therapy, and 3D Bioprinting for Glaucoma and Retinal Diseases.},
journal = {Advances in experimental medicine and biology},
volume = {1483},
number = {},
pages = {115-139},
pmid = {40131702},
issn = {0065-2598},
mesh = {Humans ; *Glaucoma/therapy/pathology/physiopathology ; *Regenerative Medicine/methods/trends ; *Bioprinting/methods/trends ; *Printing, Three-Dimensional ; *Cell- and Tissue-Based Therapy/methods/trends ; *Retinal Diseases/therapy/pathology ; Animals ; Tissue Engineering/methods ; },
abstract = {Regenerative medicine, cell therapy, and 3D bioprinting represent promising advancements in addressing retinal and glaucomatous diseases. These conditions, including diabetic retinopathy (DR), age-related macular degeneration (AMD), inherited retinal degenerations (IRDs), and glaucomatous optic neuropathy, have complex pathophysiologies that involve neurodegeneration, oxidative stress, and vascular dysfunction. Despite significant progress in conventional therapies, including anti-VEGF injections, laser photocoagulation, and intraocular pressure (IOP)-lowering interventions, these approaches remain limited in reversing disease progression and restoring lost visual function.This chapter explores the potential of emerging regenerative therapies to fill these critical gaps. For retinal diseases, cell replacement strategies using human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) have demonstrated encouraging outcomes in clinical trials, though challenges in delivery and long-term integration persist. Similarly, neuroprotective strategies and the use of retinal progenitor cells hold promise for preserving and restoring vision in degenerative retinal conditions. Advances in 3D bioprinting and retinal organoids further augment these efforts, offering innovative tools for disease modeling and therapy development.In glaucoma, regenerative approaches targeting trabecular meshwork (TM) dysfunction and retinal ganglion cell (RGC) loss are gaining traction. Stem cell-based therapies have shown potential in restoring TM functionality and providing neuroprotection, while innovative delivery systems and bioengineered platforms aim to enhance therapeutic efficacy and safety.This chapter provides an overview of the evolving landscape of regenerative therapies for retinal and glaucomatous diseases, highlighting current advancements, ongoing challenges, and future directions in the field. These approaches, while still emerging, hold the potential to transform the management of these complex ocular diseases.},
}
@article {pmid40131004,
year = {2025},
author = {Carlà, MM and Boselli, F and Giannuzzi, F and Crincoli, E and Cusato, M and Peschiaroli, S and Rizzo, S},
title = {A COMPREHENSIVE REVIEW ON THE PERIFOVEAL EXUDATIVE VASCULAR ANOMALOUS COMPLEX.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {4},
pages = {587-600},
doi = {10.1097/IAE.0000000000004376},
pmid = {40131004},
issn = {1539-2864},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Fovea Centralis/blood supply ; Fluorescein Angiography/methods ; *Retinal Vessels/abnormalities ; *Retinal Diseases/diagnosis ; Fundus Oculi ; *Vascular Malformations/diagnosis ; Exudates and Transudates ; },
abstract = {PURPOSE: The aim of this review was to summarize the most recent investigations on perifoveal exudative vascular anomalous complex (PEVAC) lesions and guide future research of this entity.<br><br>METHODS: Retrospective analysis of Cochrane Central, PubMed, Web of Science, and ClinicalTrials.gov databases for papers regarding PEVAC, looking for the following keywords: "perifoveal exudative anomalous vascular complex," "PEVAC," "PVAC," "nePVAC," "ePVAC," "deep retinal age-related microvascular anomalies," and "DRAMA."<br><br>RESULTS: PEVACs are described as a single, massive, unilateral aneurysm that frequently present with intraretinal cystic edema surrounding the fovea, active exudation and hemorrhages, usually in healthy patients. Notwithstanding this, association with age-related macular degeneration, myopia, diabetes, lamellar hole, and pachychoroid pigment epitheliopathy are frequently reported. Currently, a multimodal imaging is warranted, especially the use of OCT and OCTA can rule out several other differential diagnoses. Because of the uncertainty of the pathophysiological mechanism, the right management of these lesions are yet to be clear. Overall, laser therapy has been effective in several reports, both with thermal and micropulse type. Anti-vascular endothelial growth factor injections and steroid injections demonstrated a nonconstant response.<br><br>CONCLUSION: Several new findings are revolutionizing PEVAC management. Greater standardization could help understand the correct treatment of these lesions.},
}
@article {pmid40127748,
year = {2025},
author = {Chew, EY and Cukras, C and Duncan, JL and Dysli, C and He, Y and Henry, E and Holz, F and Moult, E and Owsley, C and Roorda, A and Sarraf, D and Schwartz, R and Spaide, R and Taylor, L and Teussink, M and Zhang, Y and Staurenghi, G},
title = {Assessing structure - Function relationships in non-neovascular age-related macular degeneration.},
journal = {Experimental eye research},
volume = {255},
number = {},
pages = {110349},
pmid = {40127748},
issn = {1096-0007},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/physiopathology/diagnosis ; Tomography, Optical Coherence/methods ; Dark Adaptation/physiology ; Visual Field Tests ; Visual Fields/physiology ; Ophthalmoscopy ; Fluorescein Angiography ; Disease Progression ; Visual Acuity/physiology ; },
abstract = {Age-related macular degeneration (AMD), a neurodegenerative disease, is the leading cause of visual impairment in industrialized countries. Challenges in defining structural/functional relationships at various stages of disease especially with non-neovascular AMD, have slowed therapeutic development. Development of such sensitive and specific markers associated with AMD progression could provide the basis necessary for future regulatory outcome variables that will be useful in assessing new, innovative AMD therapies. Advanced imaging technologies such as high-resolution optical coherence tomography, fundus autofluorescence and near infrared imaging; and functional tests including rod-mediated dark adaptation, microperimetry, fluorescence lifetime imaging ophthalmoscopy and others will be important in the evaluation of these structure/function correlations. Development of more advanced methods to study structure such as high-resolution OCT and en face OCT offer further opportunities to better correlate structure and function in clinical trials, and to better define useful biomarkers of visual outcome endpoints. Dark adaptation, although correlated with AMD stage, is difficult to incorporate as endpoint in clinical trials because dark adaptation changes slowly and the technique is time consuming. Microperimetry has become a useful outcome variable in many clinical trials and new methodology may improve its utility in structure-function correlation. These and other newer techniques will require further prospective studies to determine their clinical utility in early AMD detection, prediction of disease progression from intermediate to late stages, and the ability to monitor the advancement of non-neovascular AMD.},
}
@article {pmid40124312,
year = {2025},
author = {Wu, Z and Steffen, V and Harris, W and Cukras, CA and Ferrara, D and Guymer, RH},
title = {Reading Performance in Geographic Atrophy: Comparison of Different Reading Speed Measures for Capturing Longitudinal Changes.},
journal = {Ophthalmology science},
volume = {5},
number = {3},
pages = {100700},
pmid = {40124312},
issn = {2666-9145},
abstract = {PURPOSE: To compare different reading speed measures for capturing longitudinal visual function changes in eyes with geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>DESIGN: Analysis of data from Chroma (NCT02247479) and Spectri (NCT02247531), 2 identically designed, phase III, double-masked, randomized controlled clinical trials for lampalizumab.<br><br>PARTICIPANTS: Nine hundred forty participants aged &#x2265;50 years old with bilateral GA, who completed monocular testing of reading speed at &#x2265;3 visits over >1-year follow-up.<br><br>METHODS: Monocular reading speed was assessed using the Minnesota Low-Vision Reading Test (MNRead). Four different reading speed measures were derived and compared: reading speed of the fastest sentence read (RS1), mean reading speed of the 3 fastest sentences read (RS2), mean reading speed of the sentences larger than the critical print size (RS3), and mean reading speed of the 10 largest print sizes (termed the Reading Accessibility Index [ACC]).<br><br>MAIN OUTCOME MEASURES: Coefficient of variation (CV), with lower values reflecting better performance of a measure for capturing longitudinal change relative to interindividual variability.<br><br>RESULTS: All 4 reading speed measures showed a significant decline at 48, 72, and 96 weeks from baseline (P&#xa0;<&#xa0;0.001 for all). The CVs for ACC and RS2 (204% and 208%, respectively) were lower than for RS1 (255%; P&#xa0;&#x2264;&#xa0;0.002) and RS3 (224%; P&#xa0;&#x2265;&#xa0;0.068) for detecting change from baseline at 48 weeks, but these 2 measures were not significantly different from each other (P&#xa0;=&#xa0;0.362). There were also statistically significant, but weak, negative correlations between the change from baseline at 48 weeks for all 4 reading speed measures with GA area on fundus autofluorescence imaging (&#x3c1;&#xa0;=&#xa0;-0.13 to&#xa0;-0.15; all P&#xa0;<&#xa0;0.001).<br><br>CONCLUSIONS: The mean reading speed derived from either the 10 print sizes found in everyday life (ACC) or the fastest 3 sentences read (RS2) was better than 2 widely used measures (RS1 and RS3) at capturing progressive functional decline in eyes with GA and may be the preferred measures in future clinical trials and studies. All reading speed measures also showed an expected progressive decline over time, but they only showed a weak correlation with GA growth.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40122580,
year = {2025},
author = {Borrelli, E and Foti, C and Ulla, L and Porreca, A and Introini, U and Grassi, MO and Viggiano, P and Peronetti, M and Toscani, R and Boscia, G and Termite, AC and Gennaro, C and Marolo, P and Boscia, F and Bandello, F and Reibaldi, M},
title = {Incidence and reasons for discontinuation of anti-VEGF treatment in neovascular age-related macular degeneration.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {8},
pages = {875-881},
pmid = {40122580},
issn = {1468-2079},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Incidence ; Visual Acuity ; Aged, 80 and over ; *Ranibizumab/administration &amp; dosage ; *Withholding Treatment/statistics &amp; numerical data ; Middle Aged ; *Bevacizumab/administration &amp; dosage ; Follow-Up Studies ; },
abstract = {PURPOSE: To explore the factors and frequency of interruptions in intravitreal treatment for patients with neovascular age-related macular degeneration (AMD) and to evaluate the demographic and clinical factors linked to the reasons for discontinuation.<br><br>METHODS: In this multicentre study, patients who began anti-vascular endothelial growth factor (VEGF) treatment between January 2019 and December 2021 for treatment-na&#xef;ve neovascular exudative AMD were retrospectively analysed. The overall incidence of treatment discontinuation, along with the rates for each specific cause, was calculated. The probability of each cause of discontinuation over time from the start of treatment, as well as the risk factors associated with each case, was also determined.<br><br>RESULTS: 655 individuals (28.5%) discontinued intravitreal anti-VEGF therapy. Among the five main categories of causes for discontinuation (patient's decision against clinician's advice, continuation of therapy at another clinic, clinical decision, systemic diseases or death), clinical decision emerged as the most common reason for interruption. The qualitative evaluation of the Kaplan-Meier curves suggests a higher frequency of the clinical decision as a cause of discontinuation within the initial 2 years of treatment. Worse visual acuity increased the risk of discontinuation due to clinical decisions. Younger patients were more likely to stop anti-VEGF therapy by choice. Better visual acuity and longer distance from the clinic increased the likelihood of patients continuing treatment elsewhere.<br><br>CONCLUSIONS: The discontinuation of anti-VEGF treatment is common among individuals with neovascular AMD. Causes of discontinuation include not only clinician decisions but also those related to the patient's health and personal choices.},
}
@article {pmid40122018,
year = {2025},
author = {Chenjin, Z},
title = {Exposure assessments of cadmium and lead with age-related eye disease: A systematic review and meta-analysis.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {89},
number = {},
pages = {127631},
doi = {10.1016/j.jtemb.2025.127631},
pmid = {40122018},
issn = {1878-3252},
mesh = {Humans ; *Cadmium/adverse effects/toxicity ; *Lead/adverse effects/toxicity ; *Eye Diseases/chemically induced ; *Environmental Exposure/adverse effects ; Cataract/chemically induced ; },
abstract = {BACKGROUND: Age-related eye diseases, such as macular degeneration, cataracts, and glaucoma, are significant causes of vision loss in older adults. Emerging evidence suggests that environmental exposure to heavy metals, particularly Cadmium and lead, may play an essential role in the onset and progression of these conditions.<br><br>METHODS: This systematic review and meta-analysis aimed to evaluate the association between Cadmium and lead exposure and the risk of age-related eye diseases. A comprehensive literature search was conducted across multiple databases, including PubMed, Embase, Scopus, and Web of Science, covering studies published up to July 2024. The review included observational studies on the relationship between Cadmium or lead exposure and specific eye conditions. Data extraction and quality assessment were performed independently by two reviewers. The meta-analysis utilized a random effects model to analyze cadmium and lead levels in patient and control groups, with subgroup analyses based on the type of eye disease and study design.<br><br>RESULTS: The results revealed a significant association between cadmium exposure and an increased risk of eye diseases, particularly cataracts and glaucoma. Lead exposure was also linked to a higher risk of cataracts and macular degeneration. The study found substantial heterogeneity among the included studies, highlighting the variability in exposure assessment and population characteristics.<br><br>CONCLUSIONS: Despite these variations, the findings underscore the importance of addressing environmental exposures to toxic metals as potential risk factors for age-related eye diseases. Further research is needed to clarify the underlying mechanisms and to develop targeted interventions for reducing these risks.},
}
@article {pmid40121884,
year = {2025},
author = {Pfuhlmann, K and Koch, AK and Langhorst, J},
title = {Ginkgo biloba leaf extract EGb 761® for the treatment of various diseases: Overview of systematic reviews.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {141},
number = {},
pages = {156565},
doi = {10.1016/j.phymed.2025.156565},
pmid = {40121884},
issn = {1618-095X},
mesh = {Humans ; *Ginkgo biloba/chemistry ; Phytotherapy ; *Plant Extracts/therapeutic use/pharmacology ; Plant Leaves/chemistry ; Schizophrenia/drug therapy ; Systematic Reviews as Topic ; Tinnitus/drug therapy ; Ginkgo Extract ; },
abstract = {BACKGROUND: Ginkgo biloba leaf extract EGb 761® might have diverse therapeutic effects.<br><br>OBJECTIVE: We conducted an overview of systematic reviews (SRs) to compile the efficacy and safety of EGb 761&#xae;.<br><br>METHODS: The Cochrane Database of Systematic Reviews, MEDLINE (via PubMed), Embase (via OVID) and PROSPERO were searched from inception until July 25th, 2023 with an update on January 30th, 2025. SRs were included if they evaluated the efficacy and safety of oral treatment with EGb 761&#xae; under any clinical condition or in healthy subjects for clinical reasons, such as prevention, or for health promotion. Two authors carried out screening, selection, data extraction and risk of bias assessment (AMSTAR 2). The degree of overlap was quantified. The overview was registered a priori (PROSPERO: CRD42023423789).<br><br>RESULTS: We screened 126 articles and included reviews on neurocognitive disorders (n = 13), tinnitus, macular degeneration and schizophrenia (all n = 1). For neurocognitive disorders, most SRs were in favor of EGb 761&#xae; regarding cognition and behavioral and/or psychological symptoms, while the results for functional activities of daily living varied. EGb 761&#xae; might have positive effects on tinnitus, macular degeneration or schizophrenia: however, more evidence is needed. In general, EGb 761&#xae; appears to be safe. Methodological quality was poor in all SRs. The overall overlap of the primary studies on neurocognitive disorders was very high, and pairwise overlap varied.<br><br>CONCLUSION: EGb 761&#xae; has been studied in various reviews, particularly regarding neurocognitive disorders and has been reported to be safe in many SRs. The results must be treated with caution due to the poor quality of the SRs.},
}
@article {pmid40121188,
year = {2025},
author = {He, K and Dong, X and Yang, T and Li, Z and Liu, Y and He, J and Wu, M and Wei-Zhang, S and Kaysar, P and Cui, B and Yao, X and Zhang, L and Zhou, W and Xu, H and Wei, J and Liu, Q and Hu, J and Wang, X and Yan, H},
title = {Smoking aggravates neovascular age-related macular degeneration via Sema4D-PlexinB1 axis-mediated activation of pericytes.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2821},
pmid = {40121188},
issn = {2041-1723},
support = {82020108007//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82330031//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82122018//National Natural Science Foundation of China (National Science Foundation of China)/ ; 23JCQNJC01290//Natural Science Foundation of Tianjin City (Natural Science Foundation of Tianjin)/ ; },
mesh = {*Semaphorins/metabolism/genetics ; Animals ; Humans ; *Pericytes/metabolism/pathology ; *Macular Degeneration/metabolism/pathology/etiology ; *Choroidal Neovascularization/pathology/metabolism ; Mice ; Receptors, CXCR4/metabolism ; Male ; *Smoking/adverse effects ; Female ; *Nerve Tissue Proteins/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Chemokine CXCL12/metabolism ; *Antigens, CD/metabolism/genetics ; *Cell Adhesion Molecules, Neuronal/metabolism ; Choroid/pathology/metabolism ; Aged ; Receptors, Cell Surface ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent neuroinflammation condition and the leading cause of irreversible blindness among the elderly population. Smoking significantly increases AMD risk, yet the mechanisms remain unclear. Here, we investigate the role of Sema4D-PlexinB1 axis in the progression of AMD, in which Sema4D-PlexinB1 is highly activated by smoking. Using patient-derived samples and mouse models, we discover that smoking increases the presence of Sema4D on the surface of CD8[+] T cells that migrate into the choroidal neovascularization (CNV) lesion via CXCL12-CXCR4 axis and interact with its receptor PlexinB1 on choroidal pericytes. This leads to ROR2-mediated PlexinB1 phosphorylation and pericyte activation, thereby disrupting vascular homeostasis and promoting neovascularization. Inhibition of Sema4D reduces CNV and improves the benefit of anti-VEGF treatment. In conclusion, this study unveils the molecular mechanisms through which smoking exacerbates AMD pathology, and presents a potential therapeutic strategy by targeting Sema4D to augment current AMD treatments.},
}
@article {pmid40121055,
year = {2025},
author = {Shirakawa, A and Yasuda, H and Nakamura, S and Takajo, Y and Inamasu, S and Yomoda, S and Watanabe, S and Kuse, Y and Shimazawa, M},
title = {The anti-angiogenic effects of arctigenin on choroidal neovascularization pathogenesis.},
journal = {Journal of pharmacological sciences},
volume = {158},
number = {1},
pages = {42-51},
doi = {10.1016/j.jphs.2025.03.003},
pmid = {40121055},
issn = {1347-8648},
mesh = {*Furans/pharmacology/therapeutic use/administration &amp; dosage/isolation &amp; purification ; *Lignans/pharmacology/therapeutic use/administration &amp; dosage/isolation &amp; purification ; Animals ; *Choroidal Neovascularization/drug therapy/etiology/pathology ; Humans ; Vascular Endothelial Growth Factor A/metabolism ; *Angiogenesis Inhibitors/pharmacology/therapeutic use ; Cell Proliferation/drug effects ; Disease Models, Animal ; Phosphorylation/drug effects ; Mice, Inbred C57BL ; Endothelial Cells/drug effects ; Male ; Signal Transduction/drug effects ; Arctium/chemistry ; src-Family Kinases/metabolism ; Mice ; Cells, Cultured ; Macular Degeneration/drug therapy ; Administration, Oral ; Mitochondria/metabolism/drug effects ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is an ocular disease characterized by choroidal neovascularization (CNV), resulting in severe visual impairment. Arctigenin is a natural lignan compound from Arctium lappa L. and has anti-inflammatory and vascular normalizing effects. Here, we investigated the anti-angiogenic effects of arctigenin on CNV formation. Laser-induced CNV model mice were orally administered arctigenin at 100 mg/kg once a day for 5 days before laser irradiation. Oral administration of arctigenin suppressed CNV formation, vascular leakage, and the proliferation of endothelial cells in the CNV lesions. Treatment with arctigenin at 30 μM attenuated vascular endothelial growth factor (VEGF)-induced cell proliferation of human retinal microvascular endothelial cells (HRMECs). Moreover, arctigenin suppressed the phosphorylation of Src, which is involved in VEGF signaling. Arctigenin also inhibited VEGF-induced mitochondrial respiratory activation. These findings suggested that daily intake of arctigenin may have beneficial effects on nAMD.},
}
@article {pmid40120679,
year = {2025},
author = {Lazrak, A and Bonnafous, M and Jean-Charles, A and Ouamrane, K and Tabouillot, A and Chaoui-Boudghane, Y and Merle, H},
title = {Exploring Clinical Features of Polypoidal Choroidal Vasculopathy in Black Patients: A Cross-Sectional Study and a Comprehensive Review.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {9},
pages = {860-869},
doi = {10.1016/j.oret.2025.02.030},
pmid = {40120679},
issn = {2468-6530},
mesh = {Humans ; Cross-Sectional Studies ; *Fluorescein Angiography/methods ; Female ; Male ; Aged ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/pathology ; *Polyps/diagnosis/ethnology ; *Visual Acuity ; Fundus Oculi ; Retrospective Studies ; *Choroidal Neovascularization/diagnosis/ethnology ; *Black People ; Middle Aged ; *Choroid Diseases/diagnosis/ethnology ; Follow-Up Studies ; Aged, 80 and over ; France/epidemiology ; Polypoidal Choroidal Vasculopathy ; },
abstract = {OBJECTIVE: This study aimed to evaluate the clinical and angiographic presentation of polypoidal choroidal vasculopathy (PCV) in a large cohort of Black patients.<br><br>DESIGN: We conducted a descriptive cross-sectional analysis.<br><br>PARTICIPANTS: Out of 283 patients followed for PCV in our department, 167 cases were confirmed by indocyanine green angiography (ICGA). The remaining patients lacked ICGA imaging. Among the 167 confirmed cases, 57 patients were excluded due to significant ophthalmological comorbidities, leaving 160 affected eyes in 110 patients for analysis.<br><br>METHODS: We reviewed the most recent retinophotography, OCT, fluorescein, and ICGA images in our database. All analyzed patients were followed and underwent their examinations at the University Hospital Center of Martinique, a referral center in Fort de France primarily serving a Black population. An exploratory analysis of choroidal features was made in those who underwent enhanced depth imaging spectral-domain OCT. In parallel, a literature review on PCV was performed to contextualize our findings.<br><br>MAIN OUTCOME MEASURES: We measured visual acuity, sex ratio, patient age, characteristics of exudative phenomena, polyp location, and PCV type according to Kawamura classification.<br><br>RESULTS: Most patients were women (62.7%), with an average age of 72.2 &#xb1; 10.1 years. Among the 160 eyes, 81.9% exhibited idiopathic type 2 PCV and 52.4% showed peripapillary polyp distribution. The mean visual acuity was 0.29 &#xb1; 0.3 logarithm of the minimum angle of resolution. Soft drusen were present in 15% of eyes, and 44.5% of patients had bilateral involvement. Black patients seem to have distinctive PCV characteristics compared with other ethnic groups, with a low incidence of macular polyps (23.1%), a high incidence of peripapillary polyps (52.4%), and high incidence of bilateral involvement (42.8%).<br><br>CONCLUSIONS: This is the largest series of Afro-descendant patients with PCV ever described in the literature. Polypoidal choroidal vasculopathy in our population is primarily type 2 PCV according to Kawamura's classification, predominantly affecting women, often bilateral, with a preferentially extramacular location of the polyps. These observations may be explained by the fact that PCV in these patients is not the result of neovascularization but rather linked to a generalized disease of the choroid, such as pachychoroid.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid40120030,
year = {2025},
author = {Ajekiigbe, VO and Agbo, CE and Ogieuhi, IJ and Anthony, CS and Adewole, OA and Ahmed, B and Akingbola, A and Nwankwo, CK and Kayode, AT and Chima, UE and Adaobi, OM},
title = {Innovative approaches to treatment of eye diseases: advances in stem cell therapy use in ophthalmology.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {113},
pmid = {40120030},
issn = {1573-2630},
mesh = {Humans ; *Eye Diseases/therapy ; *Stem Cell Transplantation/methods ; *Ophthalmology/methods/trends ; },
abstract = {INTRODUCTION: The human eye, a photo-sensory organ with an array of neuronal and tissue networks, remains susceptible to damage from various diseases and disorders despite its being a flawless masterpiece. It is estimated that over 2 billion people suffer from vision loss with common causative factors such as; age-related macular degeneration (AMD), glaucoma, cataracts, diabetic retinopathy, and infections amongst others. The use of Orthodox procedures has only helped mitigate the pathology; however, it doesn't serve any substantial curative purpose. More recently, the incorporation of new therapies via ocular delivery of nanomaterials and stem cell intervention has helped to change tides in the treatment of various ophthalmic pathologies.<br><br>MAIN TEXT: This review provides an overview of the current trends and breakthroughs in ophthalmology via stem cell therapy, with emphasis on its types, mechanisms, applications, and benefits. Mesenchymal stem cells which can arise from embryonic or adult origin possess some immunomodulatory effects that contribute to the therapeutic relevance of the MSCs and the ability to evade rejection from the host. However, the major drawback has been uncontrolled growth which can result in unintended side effects. Moreso, religious and ethical issues concerning the employment of MSCs from embryonic origin have also hindered clinical progression with its use. The use of stem cell therapy in the treatment of eye pathologies which is still undergoing clinical trials has shown to be a more viable treatment approach in ophthalmology as it targets retinal degenerative diseases thereby offering novel pathways for vision restoration. And also serves as a revolutionary alternative for treating severe ocular diseases. Stem cell delivery techniques might be quite cumbersome as the eye is a very delicate organ. The therapeutic interventional technique employed is aimed to ensure the reduction or absence of undesired effects in the deposition of the active pharmaceutical ingredient (API) being the stem cells. Techniques such as hydrogel-based injectables, which offer delivery of the APIs to the desired site of action without change in the physicochemical properties of the drug molecule, the scaffold delivery techniques, and the use of 3D bio-printing which can be used to develop scaffolds for retinal degeneration. The employment of artificial intelligence and machine learning in stem cell therapy has shown to be very fast and efficient in stem cell delivery and preventing likely human errors.<br><br>CONCLUSIONS: Unlike conventional treatments that often focus on managing symptoms, stem cells have the unique ability to repair and regenerate damaged tissues, addressing the root causes of the diseases. However, limitations due to economic, regulatory, and ethical challenges have posed barriers to advancing stem cell therapies.},
}
@article {pmid40118873,
year = {2025},
author = {Bhuckory, MB and Monkongpitukkul, N and Shin, A and Kochnev Goldstein, A and Jensen, N and Shah, SV and Pham-Howard, D and Butt, E and Dalal, R and Galambos, L and Mathieson, K and Kamins, T and Palanker, D},
title = {Enhancing prosthetic vision by upgrade of a subretinal photovoltaic implant in situ.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2820},
pmid = {40118873},
issn = {2041-1723},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; FA9550-19-1-0402//United States Department of Defense | United States Air Force | AFMC | Air Force Office of Scientific Research (AF Office of Scientific Research)/ ; R01 EY035227/EY/NEI NIH HHS/United States ; R01-EY-035227//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; P30-EY-026877//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; ECCS1542152//National Science Foundation (NSF)/ ; W81XWH-22-1-0933//U.S. Department of Defense (United States Department of Defense)/ ; },
mesh = {Animals ; *Visual Prosthesis ; *Retina/surgery/physiology ; Rats ; Visual Acuity/physiology ; *Macular Degeneration/physiopathology/surgery/therapy ; Male ; Humans ; Prostheses and Implants ; },
abstract = {In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100 µm pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22 µm pixels increased the grating acuity from the 100 µm capability of PRIMA implants to 28 µm, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.},
}
@article {pmid40118382,
year = {2025},
author = {Oh, JW and Ahn, SJ and Jung, JH and Kim, TW and Kim, KP},
title = {Proteomic Analysis of Aqueous Humor Identified Clinically Relevant Molecular Targets for Neovascular Complications in Diabetic Retinopathy.},
journal = {Molecular &amp; cellular proteomics : MCP},
volume = {24},
number = {4},
pages = {100953},
pmid = {40118382},
issn = {1535-9484},
mesh = {*Diabetic Retinopathy/metabolism/complications/pathology ; Humans ; *Aqueous Humor/metabolism ; *Proteomics/methods ; Biomarkers/metabolism ; Male ; Female ; Middle Aged ; Aged ; *Glaucoma, Neovascular/metabolism ; Cataract/metabolism ; },
abstract = {Diabetic retinopathy (DR) is a leading cause of blindness in adults under 40 in the developed world, with a significant proportion progressing to vision-threatening stages such as proliferative diabetic retinopathy (PDR) and neovascular glaucoma (NVG). This study aims to explore the molecular mechanisms underlying the progression from nonproliferative DR to PDR and NVG, focusing on identifying potential biomarkers and therapeutic targets. Utilizing discovery-based proteomics, specifically label-free quantification and tandem mass tag, we analyzed aqueous humor (AH) proteins obtained during cataract surgery or anterior chamber paracentesis from patients with nonproliferative DR, PDR, and NVG. Validation of marker candidates for each disease state was conducted using triple quadrupole-MS for targeted protein quantification. Our proteomic analysis identified 2255 proteins, and gene ontology analysis and functional annotation highlighted key biological processes implicated in DR, such as lens development, immune responses, and lipid metabolism. Validation of potential biomarkers identified 20 proteins with significant concentration changes, including several candidates with diagnostic utility based on ROC curve analysis. Further investigation into clinical relevance revealed that crystallin gamma-S is strongly associated with cataract severity, highlighting its role as a potential marker for ocular complications in DR. Importantly, we identified that the pathological factors driving DR progression have a much greater impact than age, a previously known variable, in shaping the proteomic landscape of AH. Additionally, proteins associated with macular degeneration (CA1, CA2, and HBA1) were uncovered, providing new insights into overlapping mechanisms between DR and other retinal diseases. Finally, proteins linked to panretinal photocoagulation treatment, including APOB and CST6, were identified, suggesting their involvement in the therapeutic response and post-treatment adaptation. These findings underscore the potential of AH proteomics in uncovering predictive biomarkers and elucidating the molecular pathogenesis of DR and its complications.},
}
@article {pmid40118134,
year = {2025},
author = {Luan, R and Xu, S and Xu, M and Wang, M and Huang, X and Wang, J and Li, Q and Gong, Y and Liu, J and Shao, Y and Li, X},
title = {Targeting BMP4 as a therapeutic strategy for neovascularization and fibrosis in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {255},
number = {},
pages = {110348},
doi = {10.1016/j.exer.2025.110348},
pmid = {40118134},
issn = {1096-0007},
mesh = {Animals ; *Bone Morphogenetic Protein 4/antagonists &amp; inhibitors/metabolism ; Mice ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; Fibrosis/drug therapy/metabolism ; Mice, Inbred C57BL ; *Macular Degeneration/metabolism/drug therapy/pathology ; Disease Models, Animal ; *Carrier Proteins/therapeutic use/pharmacology ; Intravitreal Injections ; Cell Proliferation ; Actins/metabolism ; Cell Differentiation ; Endothelial Progenitor Cells/metabolism ; Cells, Cultured ; Male ; Myofibroblasts/metabolism ; Humans ; },
abstract = {This study investigates the role of bone morphogenetic protein-4 (BMP4) in age-related macular degeneration (AMD), with a focus on its effects on subretinal fibrosis and choroidal neovascularization (CNV). Using a mouse model of laser-induced CNV, we found that BMP4 expression was significantly elevated in CNV lesions. BMP4 was shown to promote fibroblast proliferation and their differentiation into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA). Additionally, BMP4 promoted the transition of endothelial progenitor cells (EPCs) into endothelial cells (ECs), a process that was modulated by mitochondrial function. Intravitreal administration of Noggin, a BMP4 inhibitor, significantly reduced CNV lesion volume and decreased the expression of CD31 and α-SMA, suggesting a decrease in neovascularization and fibrosis. These findings underscore BMP4's critical role in AMD pathogenesis by driving both angiogenesis and fibrosis. Targeting BMP4 with Noggin presents a promising therapeutic approach for AMD, addressing both neovascularization and fibrosis in a single intervention, and highlights BMP4 as a potential novel target for AMD therapy.},
}
@article {pmid40117903,
year = {2025},
author = {Di Marco, B and Marchetti, F and Costa, S and Baldini, E and Baldisserotto, A and Gugel, I and Vertuani, S and Strettoi, E and Manfredini, S},
title = {Dual-action steroid derivatives with anti-inflammatory and antioxidant potency: An in vitro study.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {186},
number = {},
pages = {117940},
doi = {10.1016/j.biopha.2025.117940},
pmid = {40117903},
issn = {1950-6007},
mesh = {*Anti-Inflammatory Agents/pharmacology/chemistry ; Animals ; Humans ; *Antioxidants/pharmacology ; Mice ; Cell Line ; Oxidative Stress/drug effects ; Retinal Pigment Epithelium/drug effects/metabolism ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; *Steroids/pharmacology/chemistry ; Mitochondria/drug effects/metabolism ; Hydrogen Peroxide ; },
abstract = {In a recent study, we obtained two novel cortisone-derived molecules: 1,9β,17,21- tetrahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione(SCA)and 1,9β,17,20β,21-pentahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one(SCB). These compounds showed a dual activity combining potent anti-inflammatory and antioxidant properties, suggesting their potential as therapeutic agents for conditions characterized by inflammation and oxidative stress, such as severe ocular disorders. In this study, in vitro experiments using human ARPE-19 and mouse 661 W cell lines, which model the retinal pigment epithelium and retinal photoreceptors respectively, revealed that pretreatment with SCA and SCB under oxidative stress with H2O2 preserved cell viability, reduced intracellular ROS levels, maintained tight junction integrity and Trans Epithelial Electrical Resistance (TEER). Moreover, both compounds enhanced mitochondrial respiration, thereby improving cellular bioenergetics. These results indicate that SCA and SCB could provide an effective alternative to traditional corticosteroids in treating complications in which oxidative stress and inflammation are combined, including diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Preclinical studies on animal models and trials on human ocular diseases are necessary to validate these findings in vivo and explore their therapeutic potential.},
}
@article {pmid40117439,
year = {2025},
author = {Oke, I and Fuse, K and Krüger, N and Schoeps, VA and Guetter, CR},
title = {Re: Alshaikhsalama et al.: Association between obstructive sleep apnea and age-related macular degeneration development and progression (Ophthalmol Retina. 2024 Dec 9:S2468-6530(24)00580-3. doi: 10.1016/j.oret.2024.12.004. Online ahead of print.).},
journal = {Ophthalmology. Retina},
volume = {9},
number = {5},
pages = {e41},
doi = {10.1016/j.oret.2025.02.004},
pmid = {40117439},
issn = {2468-6530},
}
@article {pmid40115778,
year = {2025},
author = {Wu, Y and Liu, Y and Jiao, Z and Chen, X and Li, H and Zhou, Y and Liu, G},
title = {Association between the weight-adjusted waist index and age-related macular degeneration in US adults aged≥40 years: the NHANES 2005-2008.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1552978},
pmid = {40115778},
issn = {2296-858X},
abstract = {OBJECTIVE: The association between the weight-adjusted waist index (WWI) and age-related macular degeneration (AMD) in US adults aged 40 years and older is unknown. The goal of this study was to ascertain a possible association between the two.<br><br>METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) in the US from 2005 to 2008. The WWI was calculated by dividing waist circumference (WC) by the square root of body weight (kg). AMD was diagnosed based on distinctive features observed in the fundus, using a standard classification system. Weighted logistic regression analyses were conducted to investigate the association between the WWI and AMD. Spline smoothing and threshold effects were applied to explore non-linear correlations. Subgroup analyses were performed to identify underlying covariates affecting this relationship. In addition, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of the WWI for AMD.<br><br>RESULTS: A total of 5,132 participants were enrolled in this study. The results showed a significant positive association between the WWI and risk of AMD (OR&#x202f;=&#x202f;1.76 (1.52, 2.04); p&#x202f;<&#x202f;0.0001). When the WWI was categorized into tertiles, the highest group exhibited a stronger association compared to the lowest tertile (OR&#x202f;=&#x202f;2.90 (2.18, 3.86); p&#x202f;<&#x202f;0.0001) in model 1. The subgroup analyses and interaction tests indicated that the relationship between the WWI and AMD was stable across various populations. The spline smoothing and threshold effects showed a positive non-linear correlation between the WWI and AMD incidence. Furthermore, compared to body mass index (BMI), WC, and weight, the WWI showed better predictability for AMD, as shown by the ROC analysis.<br><br>CONCLUSION: There exists a positive non-linear association between the WWI and AMD in US adults aged 40&#x202f;years and older. The WWI-related obesity management is necessary for the prevention and treatment of AMD.},
}
@article {pmid40115389,
year = {2025},
author = {Jia, R and Yin, Y and Shan, H},
title = {Systemic inflammatory response index as a novel biomarker for age-related macular degeneration: a cross-sectional study from NHANES (2005-2008).},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1540933},
pmid = {40115389},
issn = {2296-861X},
abstract = {BACKGROUND: Chronic low-grade systemic inflammation plays a significant role in age-related macular degeneration (AMD) pathogenesis. The systemic inflammatory response index (SIRI), a novel inflammatory marker, may predict various diseases. However, data on the relationship between SIRI and AMD are limited. This study examines the relationship between SIRI and AMD and assesses its potential as a predictive biomarker.<br><br>METHODS: A cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2008 was conducted on participants aged &#x2265;40&#x202f;years with SIRI and AMD status data. Multivariable logistic regression models adjusted for confounders were used to assess the association. Sensitivity and subgroup analyses, along with restricted cubic spline (RCS) curve analysis, were performed.<br><br>RESULTS: Among 5,365 participants, 425 (7.9%) had AMD. The median SIRI was higher in AMD patients (1.23 vs. 1.04, p&#x202f;<&#x202f;0.001). Higher SIRI was independently associated with increased odds (adjusted OR: 1.18, 95% CI:1.07-1.29, p&#x202f;=&#x202f;0.001). RCS analyses revealed a dose-response relationship (p&#x202f;=&#x202f;0.002). Subgroup analyses showed a positive association in male participants, individuals with hypertension, individuals with obesity, and non-smokers. Higher SIRI levels were independently associated with increased AMD risk (adjusted OR: 1.27, 95% CI: 1.03-1.56, p&#x202f;=&#x202f;0.023).<br><br>CONCLUSION: Elevated SIRI is independently associated with increased AMD risk in the U.S. population. SIRI may serve as a biomarker for identifying high-risk individuals, enabling early intervention. The cross-sectional design limits causal inference, and unmeasured confounders may affect the results. SIRI could potentially serve as a non-invasive biomarker for AMD risk, pending further validation through longitudinal studies.},
}
@article {pmid40114029,
year = {2025},
author = {Matagrin, B and Fenniri, I and Chirpaz, N and Billant, J and Agard, E and Chudzinski, R and Burillon, C and Dot, C},
title = {SIRE: Short interval in real life Does intensive anti-VEGF treatment in the first year predict subsequent treatment burden in exudative age-related macular degeneration?.},
journal = {Eye (London, England)},
volume = {39},
number = {9},
pages = {1797-1804},
pmid = {40114029},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Ranibizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Intravitreal Injections ; Visual Acuity/physiology ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Tomography, Optical Coherence ; Follow-Up Studies ; Fluorescein Angiography ; Time Factors ; Treatment Outcome ; },
abstract = {BACKGROUND: Anti-VEGF's have changed the prognosis of exudative age-related macular degeneration (AMD). Ranibizumab and aflibercept have proven their functional efficacy, but their use has revealed in real life a wide variety of patient profiles with varied responses to treatment. This work focused on patients receiving "intensive" IVT treatment with a sustained injection rhythm, also referred to as having a high treatment burden.<br><br>OBJECTIVE: The main objective of this work was to determine, in real-life conditions, the proportion of patients receiving "intensive" treatment among those being followed for exudative AMD. Secondary objectives were to analyse the long-term functional outcomes of these patients, their anatomical characteristics, and the evolution of their treatment regimen.<br><br>METHOD: A retrospective descriptive single-centre real-life study was conducted on patients treated for exudative AMD with intensive treatment (intervals of less than 8 weeks during the first year of treatment). A subgroup analysis compared patients who exceeded Q8 during follow-up (Group 1) versus patients remaining in intensive treatment (Group 2).<br><br>RESULTS: A total of 301 records were analysed, with 24.9% of the eyes (n&#x2009;=&#x2009;75) considered under intensive treatment. The mean age was 84 years (&#x2009;&#xb1;&#x2009;7.5), and 61% were men. Type 1 choroidal neovascularization (CNV) accounted for 64% of our cohort, type 2 CNV represented 29.3%, and type 3 was involved in 6.7%. The mean follow-up was 5.6 years (&#x2009;&#xb1;&#x2009;3.6), with an average number of 41 IVT (&#x2009;&#xb1;&#x2009;26.7). Visual acuity was maintained at 0.53 (&#x2009;&#xb1;&#x2009;0.2) baseline vs. 0.61 (&#x2009;&#xb1;&#x2009;0.2) after 5 years of follow-up (p&#x2009;=&#x2009;0.02). Central retinal thickness (CRT) and subretinal fluid (SRF) were significantly reduced during our follow-up, and PED height remained stable. Almost half of the eyes (44%) had an extension of their interval (&#x2009;>&#x2009;Q8) beyond the first year; however, this objective was achieved on average after 4.5 years of treatment. The visual acuity of Group 2 (&#x2009;<&#x2009;Q8), despite receiving more injections, was superior to that of Group 1 (&#x2009;>&#x2009;Q8) with baseline values of 0.57 (&#x2009;&#xb1;&#x2009;0.2) and 0.48 (&#x2009;&#xb1;&#x2009;0.2) (p&#x2009;=&#x2009;0.161) respectively, and at 5 years 0.79 (&#x2009;&#xb1;&#x2009;0.2) and 0.54 (&#x2009;&#xb1;&#x2009;0.2) (p&#x2009;=&#x2009;0.026). Similarly, CRT, PED height, and SRF were higher in Group 2. The distribution of neovascular types showed more type 2 in Group 1 (45.5% vs. 16.7%).<br><br>CONCLUSION: Patients requiring intensive treatment represent about &#xbc; of our AMD patient population. Despite the high treatment burden, these patients maintain their visual acuity at 5 years. An extension of intervals is observed in nearly half of the patients, occurring late. Intensive treatment during the first year appears to be predictive of a future hight treatment burden.},
}
@article {pmid40112947,
year = {2025},
author = {Kong, M and Li, J and Jin, R and Zhang, Y and You, J and Wang, N and Tong, N},
title = {Lycium barbarum polysaccharide alleviates H2O2-induced premature senescence by downregulating miRNA-34a-5p in ARPE-19 cells.},
journal = {Cell stress &amp; chaperones},
volume = {30},
number = {3},
pages = {130-142},
pmid = {40112947},
issn = {1466-1268},
mesh = {*Hydrogen Peroxide/pharmacology/toxicity ; *MicroRNAs/metabolism/genetics ; Humans ; *Cellular Senescence/drug effects ; Cell Line ; *Down-Regulation/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; *Drugs, Chinese Herbal/pharmacology ; Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Apoptosis/drug effects ; Cell Survival/drug effects ; },
abstract = {The premature senescence of retinal pigment epithelium (RPE) plays a significant role in the development of age-related macular degeneration. This study aimed to investigate the potential protective effect of Lycium barbarum polysaccharide (LBP) against H2O2-induced premature senescence and to elucidate the underlying mechanisms. The ARPE-19 cell line was subjected to H2O2 exposure to create a model of premature senescence. The modulation of microRNA-34a-5p expression was accomplished using antagomir and agomir, as assessed by quantitative real-time polymerase chain reaction. The senescence model was successfully established by treating cells with 200 μM H2O2 for 2 hours daily over a span of three consecutive days. This oxidative stress resulted in a notable increase in the proportion of senescence-associated beta-galactosidase-positive cells, reaching 33.5%, without significant alterations in cell viability or apoptosis. In the ARPE-19 cells undergoing premature senescence, there was a marked increase in reactive oxygen species (ROS) production and malondialdehyde levels, coupled with a significant decrease in the activity of total superoxide dismutase, glutathione peroxidase, and catalase. Additionally, microRNA-34a-5p was found to be overexpressed in these cells. Treatment with LBP alleviated H2O2-induced premature senescence, diminished the overexpression of microRNA-34a-5p, and suppressed ROS production. Moreover, the incubation with ago-34a reversed the protective effect of LBP in ARPE-19 cells. In conclusion, the overexpression of microRNA-34a-5p contributes to the H2O2-induced premature senescence of ARPE-19 cells. LBP appears to mitigate this premature senescence, at least in part, by downregulating microRNA-34a-5p expression and reducing oxidative stress.},
}
@article {pmid40112264,
year = {2025},
author = {Gu, Z and Luo, X and Sun, R and Xi, T and Zhang, C},
title = {Long-term effects of the COVID-19 lockdown on the structural and functional outcomes of neovascular AMD patients in Suzhou, China.},
journal = {PloS one},
volume = {20},
number = {3},
pages = {e0319677},
pmid = {40112264},
issn = {1932-6203},
mesh = {Humans ; *COVID-19/epidemiology/prevention &amp; control ; Male ; Female ; Aged ; Retrospective Studies ; China/epidemiology ; Visual Acuity ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; SARS-CoV-2 ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; *Macular Degeneration/drug therapy/pathology ; Quarantine ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: Timely anti-vascular endothelial growth factor (VEGF) therapy is essential for visual function in neovascular age-related macular degeneration (nAMD). The coronavirus pandemic has led to unprecedented delays in anti-VEGF intravitreal therapy because of the need to reduce hospital attendance.<br><br>OBJECTIVES: To assess the long-term impact of COVID-19 pandemic-related delays in intravitreal anti-VEGF therapy on nAMD patients.<br><br>METHODS: This was a retrospective study of 98 patients (102 eyes) with nAMD whose anti-VEGF treatments were interrupted for >&#x2009; 8 weeks due to the COVID-19 pandemic. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and anatomical characteristics on spectral domain optical coherence tomography (SD-OCT) were measured at baseline, at the last follow-up visit before treatment interruption (V0), at the first visit after the COVID-19 lockdown had ended (V1), at the six-month follow-up (V-6 months) and at the final visit at the 1-year follow-up (V-final). The control group included nAMD patients who had completed at least three anti-VEGF treatments and received consecutive follow-up with timely anti-VEGF treatments for one year.<br><br>RESULTS: After one year of regular follow-up and standardized treatment, the treatment-interrupted group (TIG) had significantly worse visual acuity than the treatment-continuous group (TCG) (0.71&#x2009;&#xb1;&#x2009;0.38 vs. 0.52&#x2009;&#xb1;&#x2009;0.32, p&#x2009;<&#x2009;0.001); however, there was no significant difference between the groups in the mean CRT (273.95&#x2009;&#xb1;&#x2009;112.96 &#xb5;m vs. 261.43&#x2009;&#xb1;&#x2009;90.66 &#xb5;m, p&#x2009;>&#x2009;0.05). Furthermore, subgroup analysis revealed that, compared with those before treatment interruption, the BCVA of the TIG patients slightly improved, but the mean CRT and related activity indices returned to baseline values according to OCT imaging (all p&#x2009;>&#x2009;0.05). Multiple linear regression analysis revealed that longer treatment interruption was associated with greater deterioration in visual acuity (p&#x2009;=&#x2009;0.009).<br><br>CONCLUSION: Treatment interruption for more than 8 weeks had a sustained negative impact on visual acuity in treated eyes one year later. For nAMD patients, continuous treatment, regardless of the underlying regimen, remains critical.},
}
@article {pmid40111518,
year = {2025},
author = {Nam, KT and Yun, C},
title = {Long-term visual outcomes of patients with neovascular age-related macular degeneration treated with anti-VEGF therapy lost to follow-up.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {7},
pages = {1837-1845},
pmid = {40111518},
issn = {1435-702X},
mesh = {Humans ; *Visual Acuity ; Retrospective Studies ; Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Female ; Intravitreal Injections ; Follow-Up Studies ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage ; Aged ; *Bevacizumab/administration &amp; dosage ; Time Factors ; Tomography, Optical Coherence/methods ; *Lost to Follow-Up ; Fluorescein Angiography ; Aged, 80 and over ; Treatment Outcome ; Fundus Oculi ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; },
abstract = {PURPOSE: To evaluate the long-term visual outcomes of patients with neovascular age-related macular degeneration (AMD) who were lost to follow-up (LTFU) during treatment compared with those with continuous follow-up (CFU).<br><br>METHODS: A retrospective study was conducted on patients diagnosed with neovascular AMD who received anti-VEGF therapy from 2010 to 2022. The patients were classified into the long-term LTFU group (LTFU for more than 6&#xa0;months), the short-term LTFU group (LTFU for 2&#xa0;months to less than 6&#xa0;months), and the CFU group. We conducted a comparative analysis of baseline characteristics, factors related to visual prognosis, and differences in the occurrence of severe vision loss.<br><br>RESULTS: A total of 169 patients were classified into 43 in the long-term LTFU group, 57 in the short-term LTFU group, and 69 in the CFU group. The mean follow-up duration was 57.12&#x2009;&#xb1;&#x2009;31.68&#xa0;months. There was no significant difference in baseline visual acuity (logMAR) among the long-term LTFU, short-term LTFU, and CFU groups (0.76&#x2009;&#xb1;&#x2009;0.54, 0.68&#x2009;&#xb1;&#x2009;0.51, and 0.72&#x2009;&#xb1;&#x2009;0.54, respectively; P&#x2009;=&#x2009;0.734). The final visual acuity was significantly lower in the long-term LTFU group (1.12&#x2009;&#xb1;&#x2009;0.79) compared with the short-term LTFU group (0.65&#x2009;&#xb1;&#x2009;0.62) and the CFU group (0.65&#x2009;&#xb1;&#x2009;0.56) (P&#x2009;<&#x2009;0.001), and the change in visual acuity was significantly greater in the long-term LTFU group (0.36&#x2009;&#xb1;&#x2009;0.69) compared with the short-term LTFU group (-0.03&#x2009;&#xb1;&#x2009;0.64) and the CFU group (-0.07&#x2009;&#xb1;&#x2009;0.58) (P&#x2009;=&#x2009;0.001). Long-term LTFU was significantly associated with changes in visual acuity from the baseline to the final visit (P&#x2009;=&#x2009;0.002) and severe vision loss (P&#x2009;=&#x2009;0.002).<br><br>CONCLUSION: In patients with neovascular AMD, those LTFU for more than six months during treatment had worse long-term visual outcomes compared to those with regular follow-up or shorter LTFU durations.},
}
@article {pmid40111356,
year = {2025},
author = {Szczepan, M and Llorián-Salvador, M and Yi, C and Hughes, D and Mack, M and Chen, M and Xu, H},
title = {Differential Roles of Macrophages and Microglia in Subretinal Fibrosis Secondary to Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {3},
pages = {41},
pmid = {40111356},
issn = {1552-5783},
mesh = {Animals ; *Microglia/pathology/metabolism/physiology ; *Macrophages/physiology/pathology/metabolism ; Mice ; Fibrosis/etiology ; Mice, Inbred C57BL ; Disease Models, Animal ; Receptors, CCR2/metabolism ; CX3C Chemokine Receptor 1/metabolism ; Retinal Pigment Epithelium/pathology/metabolism ; *Retina/pathology ; *Wet Macular Degeneration/complications/metabolism/pathology ; Choroidal Neovascularization ; Immunohistochemistry ; Monocytes ; *Macular Degeneration/complications ; Real-Time Polymerase Chain Reaction ; },
abstract = {PURPOSE: To investigate the differential role of infiltrating CCR2+ macrophages and CX3CR1+ microglia in neovascular AMD (nAMD)-mediated subretinal fibrosis.<br><br>METHODS: Subretinal fibrosis was induced using the two-stage laser protocol in C57BL/6J or CX3CR1gfp/+ mice. The fibrotic lesion was detected using collagen-1 staining in retinal pigment epithelial /choroidal flatmounts. Infiltrating macrophages and microglial were identified using F4/80, CCR2, and CX3CR1 markers at one, three, six, and 10&#xa0;days after the second laser. Circulating CCR2+ monocytes were depleted using the MC-21 antibody, whereas CX3CR1+ microglia were depleted using PLX5622. BV2 microglia were treated with TGF-&#x3b2;1 for 96 hours, and their profibrotic potential was examined by quantitative PCR and immunocytochemistry.<br><br>RESULTS: Subretinal fibrosis lesions developed three days after the second laser, accompanied by persistent CCR2+F4/80+ macrophage and CX3CR1+ cell infiltration. Inflammation in the first three days after the second laser was dominated by filtrating CX3CR1+ cells, and the number increased until day (D) 10 post-second laser. Depletion of CCR2+ monocytes from D5-10 significantly reduced the vascular and fibrotic components of the lesion, while CX3CR1+ cell depletion reduced Isolectin B4+ but not collagen-1+ lesion size. Bone marrow-derived macrophages from D6 and D10 mice expressed significantly higher levels of &#x3b1;-smooth muscle actin (&#x3b1;-SMA) and collagen-1 compared to cells from D1 and D3. TGF&#x3b2;1 treatment increased TMEM119, CX3CR1, IL1b and iNOS gene expression but did not affect Acta2 and Col1a1 gene expression in BV2 cells.<br><br>CONCLUSIONS: CCR2+ monocytes, but not CX3CR1+ microglia, critically contribute to the development of subretinal fibrosis in nAMD.},
}
@article {pmid40110744,
year = {2025},
author = {Nie, J and Eom, K and AlGhosain, HM and Neifert, A and Cherian, A and Gerbaka, GM and Ma, KY and Liu, T and Lee, J},
title = {Intravitreally Injected Plasmonic Nanorods Activate Bipolar Cells with Patterned Near-Infrared Laser Projection.},
journal = {ACS nano},
volume = {19},
number = {12},
pages = {11823-11840},
pmid = {40110744},
issn = {1936-086X},
support = {R01 EY030569/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Nanotubes/chemistry ; *Gold/chemistry/administration &amp; dosage ; Mice ; Infrared Rays ; *Lasers ; Intravitreal Injections ; *Retinal Bipolar Cells/drug effects ; Mice, Inbred C57BL ; },
abstract = {Retinal prostheses aim to restore vision in individuals affected by degenerative conditions, such as age-related macular degeneration and retinitis pigmentosa. Traditional approaches, including implantable electrode arrays and optogenetics, often require invasive surgery or genetic modification and face limitations in spatial resolution and visual field size. While emerging nanoparticle-based methods offer minimally invasive solutions, some of them rely on intense visible light, which may interfere with residual vision. Plasmonic gold nanorods (AuNRs), tuned to absorb near-infrared (NIR) light, provide a promising alternative by enabling photothermal neuromodulation without affecting the remaining sight. However, effectively utilizing photothermal stimulation with patterned laser projection for precise neural activation remains underexplored. In this study, we introduce a less invasive approach using intravitreally injected anti-Thy1 antibody-conjugated AuNRs to primarily activate bipolar cells─a target traditionally reached through more invasive subretinal injections. This technique allows for extensive retinal coverage and facilitates high-resolution visual restoration via patterned NIR stimulation. Following injection, a scanning NIR laser beam projected in a square pattern with a spot size of 20 μm consistently triggered highly localized neuronal activation, specifically stimulating bipolar cells through temperature-sensitive ion channels. In vivo, this patterned stimulation evoked electrocorticogram responses in the visual cortex of both wild-type and fully blind mouse models without inducing systemic toxicity or significant retinal damage. Our innovative approach promises significant advancements in spatial resolution and broad applicability, offering a precise, customizable, and less invasive method to restore vision.},
}
@article {pmid40109457,
year = {2025},
author = {Dai, L and Ye, S and Song, Z and Song, J},
title = {[Berberine Alleviates Chronic Retinal Light Damage in Mice: A Study of the Role of P2X7R and the Mechanisms Involved].},
journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition},
volume = {56},
number = {1},
pages = {35-40},
pmid = {40109457},
issn = {1672-173X},
mesh = {Animals ; *Receptors, Purinergic P2X7/metabolism/physiology/genetics ; *Berberine/pharmacology ; Mice ; *Retina/radiation effects/drug effects/pathology ; *Light/adverse effects ; Apoptosis/drug effects ; Male ; },
abstract = {OBJECTIVE: To investigate the trend of dynamic changes and the mechanisms of P2X7R by which berberine (BBR) alleviates chronic retinal light injury in mice.<br><br>METHODS: A total of 90 mice were randomly divided into three groups, a blank control group (n = 10), a group exposed to low-intensity blue light (500 lux) for 12 hours per day for a duration of 3 months, which was referred to as the LD group (n = 40), and another group given BBR at a dose of 200 mg/kg via gastric gavage on top of the blue light exposure for the LD group, which was referred to as the LD + BBR group (n = 40). After the light exposure and gavage were completed, eye tissues were collected from the mice. Hematoxylin and eosin (HE) staining was performed to observe the protective effects of berberine on chronic retinal light damage in mice. TUNEL assay was performed to assess the effect of berberine on apoptotic cells in mice with chronic retinal light injury. Additionally, quantitative polymerase chain reaction (QPCR) was performed to assess the expression level of P2X7 receptors in chronic retinal light injury relieved by BBR.<br><br>RESULTS: Compared with the blank control group, the LD group exhibited abnormal retinal morphology, with some ganglion cells displaying reduced nuclei, a deeper stain, and loose arrangement. In the LD group, the cells in the inner nuclear layer appeared to be slightly more loosely arranged, while the cells in the outer nuclear layer cells were arranged in a disorderly way. Furthermore, the thickness of the outer nuclear layer of the retina from mice in the LD group was (47.11 &#xb1; 2.01) &#x3bc;m, and a significant number of apoptotic cells were observed in the outer nuclear layer, resulting in an apoptosis rate of (71.16 &#xb1; 5.99)% (P < 0.05). In contrast, the LD + BBR group showed mild abnormal retinal morphology with loosely arranged ganglion cells. In the LD + BBR group, the cells in both inner and outer nuclear layers of retina exhibited relatively intact morphology, uniform staining pattern, and tight arrangement. Moreover, the thickness measurement for outer nuclear layer revealed a value of (54.07 &#xb1; 2.05) &#x3bc;m, and there were only a few apoptotic cells present, resulting in an apoptotic rate of (16.02 &#xb1; 2.68)% (P < 0.05). Compared with that of the blank control group, the relative expression of P2X7R mRNA in the retinas of the LD group was upregulated, with the difference between the two groups being statistically significant (P < 0.05). The relative expression of P2X7R mRNA in the retinas of the LD + BBR group was downregulated, showing no statistical significance compared with that of the blank control group. However, compared with that of the LD group, the relative expression of P2X7R mRNA in the retinas of the LD + BBR group showed a significant downward trend, and the difference between the two groups was statistically significant (P < 0.05).<br><br>CONCLUSION: Berberine can alleviate chronic retinal photodamage in mice, and inhibit the activation of P2X7R, thereby preventing the formation of retinal photodamage.},
}
@article {pmid40108376,
year = {2025},
author = {Kim, J and Moon, SY and Kang, HG and Kim, HJ and Choi, JS and Lee, SHS and Park, K and Won, SY},
title = {Therapeutic potential of AAV2-shmTOR gene therapy in reducing retinal inflammation and preserving endothelial Integrity in age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {9517},
pmid = {40108376},
issn = {2045-2322},
support = {HN22C0245//This research was supported by the Korea Drug Development Fund, funded by the Ministry of Science and ICT, the Ministry of Trade, Industry, and Energy, and the Ministry of Health and Welfare (HN22C0245, Republic of Korea)./ ; },
mesh = {Humans ; *Macular Degeneration/therapy/genetics/pathology/metabolism ; TOR Serine-Threonine Kinases/metabolism/genetics ; *Genetic Therapy/methods ; Tumor Necrosis Factor-alpha/metabolism/pharmacology ; Inflammation/therapy/genetics ; Animals ; Human Umbilical Vein Endothelial Cells/metabolism ; *Dependovirus/genetics ; Retina/pathology/metabolism ; Signal Transduction ; Interleukin-1beta/metabolism ; Microglia/metabolism ; Interleukin-6/metabolism ; NF-kappa B/metabolism ; Tight Junctions/metabolism ; Cell Line ; Genetic Vectors/genetics ; Endothelial Cells/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent retinal disorder that leads to central vision loss, mainly due to chronic inflammation. Tumor necrosis factor-alpha (TNF-α) is a critical mediator of inflammatory responses within the retinal environment. This study has investigated TNF-α's influence on inflammatory cytokine production and endothelial barrier integrity in human microglial (HMC3) and endothelial (HUVEC) cells. We found that TNF-α significantly elevated the expression and secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in HMC3 cells and disrupted endothelial tight junctions in HUVECs, as evidenced by weakened ZO-1 staining and compromised barrier function. To mitigate these effects and further investigate the in vitro mechanism of actions in CRG-01's in vivo therapeutic efficacy of anti-inflammation, we employed AAV2-shmTOR, CRG-01, as the candidate for therapeutic vector targeting the mammalian target of the rapamycin (mTOR) pathway. TNF-α-induced IL-6, IL-1β, and NF-κB signaling in HMC3 cells were significantly reduced by AAV2-shmTOR treatment, which may present a promising avenue for the fight against AMD. It also effectively preserved endothelial tight junction integrity in TNF-α-treated HUVECs, providing reassurance about its effectiveness. Furthermore, the supernatant medium collected from AAV2-shmTOR-treated HMC3 cells decreased oxidative stress, protein oxidation, and cytotoxicity in ARPE retinal pigment epithelial cells. These results strongly suggested that CRG-01, the candidate therapeutic vector of AAV2-shmTOR, may have a therapeutic potential to treat AMD-related retinal inflammation.},
}
@article {pmid40108164,
year = {2025},
author = {Dai, X and Yang, X and Feng, Y and Wu, X and Ju, Y and Zou, R and Yuan, F},
title = {The role of vitamin K and its antagonist in the process of ferroptosis-damaged RPE-mediated CNV.},
journal = {Cell death &amp; disease},
volume = {16},
number = {1},
pages = {190},
pmid = {40108164},
issn = {2041-4889},
support = {81873680//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81970817//National Natural Science Foundation of China (National Science Foundation of China)/ ; 24ZR1411400//Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)/ ; },
mesh = {Animals ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; *Choroidal Neovascularization/pathology/metabolism/drug therapy ; *Ferroptosis/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Humans ; Mice ; *Vitamin K/antagonists &amp; inhibitors/pharmacology/metabolism ; Mice, Inbred C57BL ; Macular Degeneration/pathology/drug therapy ; Activating Transcription Factor 4/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in people over the age of 55. AMD currently affects approximately 8% of the world's population, and the number is growing as the global population ages. Growing evidence suggests that pathological choroidal neovascularization (CNV) is often related to more severe and rapid vision loss and blindness associated with AMD. The typical clinical treatment is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond well to this therapy, and the potential risks of long-term repeated injections cannot be ignored. Therefore, there is an urgent need to explore the specific mechanisms of CNV development and find new, safe, and effective treatments. In this study, our data indicate that ferroptotic damage of retinal pigment epithelium (RPE) and its induced VEGFA overexpression are critical promoting factors in the development of CNV. Vitamin K can mediate the protection of RPE cells from ferroptotic damage and regulate the expression of eIF2α-ATF4-VEGFA in a VKOR/FSP1-dependent manner, inhibiting new angiogenesis to alleviate CNV. On the contrary, vitamin K antagonists (VKA) represented by warfarin, can promote RPE ferroptotic damage and related vascular proliferation in mice and eventually aggravate CNV lesions. However, vitamin K still showed significant protective effects even in the presence of VKA. Due to its significant anti-ferroptosis and anti-neovascular effects, as well as its relative safety and convenience of use, vitamin K has excellent potential in the treatment of CNV and is expected to become a clinically effective and safe new CNV treatment strategy.},
}
@article {pmid40107501,
year = {2025},
author = {Danzig, CJ and Dinah, C and Ghanchi, F and Hattenbach, LO and Khanani, AM and Lai, TYY and Shimura, M and Abreu, F and Arrisi, P and Liu, Y and Paris, LP and Retiere, AC and Willis, JR and Schlottmann, PG and , },
title = {Faricimab Treat-and-Extend Dosing for Macular Edema Due to Retinal Vein Occlusion: 72-Week Results from the BALATON and COMINO Trials.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {9},
pages = {848-859},
doi = {10.1016/j.oret.2025.03.005},
pmid = {40107501},
issn = {2468-6530},
mesh = {Humans ; *Retinal Vein Occlusion/complications/diagnosis/drug therapy ; *Macular Edema/etiology/drug therapy/diagnosis ; Double-Blind Method ; Male ; *Visual Acuity ; Female ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Dose-Response Relationship, Drug ; Follow-Up Studies ; Aged ; Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Time Factors ; *Macula Lutea/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography/methods ; Fundus Oculi ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To assess the efficacy, durability, and safety of dual angiopoietin-2/VEGF inhibition with faricimab dosed per a modified treat-and-extend-based regimen in patients with retinal vein occlusion.<br><br>DESIGN: Single-arm treatment period after a randomized, double-masked, active comparator-controlled period in the phase III BALATON/COMINO (NCT04740905/NCT04740931) trials.<br><br>PARTICIPANTS: Patients with treatment-na&#xef;ve foveal center-involved macular edema due to branch (BALATON; N = 553) or central/hemiretinal (COMINO; N = 729) retinal vein occlusion.<br><br>METHODS: Patients randomized to faricimab 6.0 mg every 4 weeks (Q4W) or aflibercept 2.0 mg Q4W up to week 20 received faricimab 6.0 mg dosed per a modified treat-and-extend-based regimen from week 24 to 72. The dosing frequency was adjusted from Q4W to Q16W based on changes in central subfield thickness (CST) and best-corrected visual acuity.<br><br>MAIN OUTCOME MEASURES: Change from baseline through week 72 in best-corrected visual acuity and CST; durability and safety through week 72.<br><br>RESULTS: Visual acuity gains and CST reductions achieved at week 24 were maintained through week 72. Adjusted mean best-corrected visual acuity (95.03% confidence interval [CI]) changes from baseline averaged over weeks 64, 68, and 72 in the prior faricimab Q4W and prior aflibercept Q4W arms were +18.1 letters (16.9-19.4) and +18.8 letters (17.5-20.0), respectively, in BALATON and +16.9 letters (15.2-18.6) and +17.1 letters (15.4-18.8), respectively, in COMINO. Adjusted mean (95.03% CI) CST changes from baseline averaged over weeks 64, 68, and 72 in the prior faricimab Q4W and prior aflibercept Q4W arms were -310.9 &#x3bc;m (-315.6 to -306.3) and -307.0 &#x3bc;m (-311.7 to -302.3), respectively, in BALATON and -465.9 &#x3bc;m (-472.5 to -459.3) and -460.6 &#x3bc;m (-467.2 to -453.9), respectively, in COMINO. In the prior faricimab Q4W and prior aflibercept Q4W arms, 64.1% and 56.9% of patients from BALATON and 45.5% and 50.1% from COMINO, respectively, were on &#x2265;Q12W dosing at week 68. Faricimab continued to be well tolerated from weeks 24 to 72; the safety profile was consistent with that established for diabetic macular edema and neovascular age-related macular degeneration.<br><br>CONCLUSIONS: These findings support the sustained efficacy and safety of faricimab in patients with macular edema due to retinal vein occlusion up to 72 weeks, with the potential for reduced treatment burden due to response durability.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40107466,
year = {2025},
author = {Pan, W and Sun, R and Yu, Y and Liu, Y and Mu, Y and Gong, H and Fan, H and Zhang, Y and He, L and He, H and Gou, J and Tang, X and Yin, T and Zhang, Y},
title = {Baicalein nanoemulsion in situ GEL for dry age-related macular degeneration.},
journal = {International journal of pharmaceutics},
volume = {675},
number = {},
pages = {125494},
doi = {10.1016/j.ijpharm.2025.125494},
pmid = {40107466},
issn = {1873-3476},
mesh = {Animals ; Emulsions ; *Flavanones/administration &amp; dosage/chemistry/pharmacokinetics/pharmacology ; *Macular Degeneration/drug therapy/metabolism ; Mice ; Mice, Inbred C57BL ; Drug Delivery Systems ; Gels ; Male ; Disease Models, Animal ; *Nanoparticles/chemistry ; Administration, Ophthalmic ; Cytokines/metabolism ; },
abstract = {Effective management of posterior ocular segment disorders necessitates sustained retinal drug delivery and rational therapeutic selection. Despite significant advances, developing drug delivery systems that simultaneously achieve deep tissue penetration and prolonged ocular surface retention remains challenging. To bridge this gap, we engineered a borneol- decorated baicalein nanoemulsion in-situ gel (Bor/Bai-N@GEL) ophthalmic formulation for dry age-related macular degeneration (d-AMD). The system integrates a borneol-decorated baicalein nanoemulsion with an ion- sensitive hydrogel. Comparative analysis revealed Bor/Bai-N@GEL's superior therapeutic performance, attributable to the prolonged ocular residence time and enhanced transcorneal permeability. Pharmacodynamic profiling demonstrated marked attenuation of inflammatory cytokines, oxidative markers, and apoptotic signaling in murine d-AMD models. In summary, our work provided a meaningful delivery strategy and research basis to treat fundus diseases. This approach offers the potential to conveniently treat early-stage d-AMD at home, improving patient adherence and overall treatment outcomes.},
}
@article {pmid40107443,
year = {2025},
author = {Clark, SJ and Curcio, C and Dick, AD and Doyle, S and Edwards, M and Flores-Bellver, M and Hass, D and Lennon, R and Toomey, CB and Rohrer, B},
title = {Breaking Bruch's: How changes in Bruch's membrane influence retinal homeostasis.},
journal = {Experimental eye research},
volume = {255},
number = {},
pages = {110343},
doi = {10.1016/j.exer.2025.110343},
pmid = {40107443},
issn = {1096-0007},
}
@article {pmid40107215,
year = {2025},
author = {Li, Y and Zhang, Y and Kam, KW and Chan, P and Liu, D and Zaabaar, E and Zhang, XJ and Ho, M and Ng, MP and Ip, P and Young, A and Pang, CP and Tham, CC and Kwan, MP and Chen, LJ and Yam, JC},
title = {Associations of long-term joint exposure to multiple ambient air pollutants with the incidence of age-related eye diseases.},
journal = {Ecotoxicology and environmental safety},
volume = {294},
number = {},
pages = {118052},
doi = {10.1016/j.ecoenv.2025.118052},
pmid = {40107215},
issn = {1090-2414},
mesh = {Humans ; *Air Pollutants/adverse effects/analysis ; Incidence ; Male ; Female ; Middle Aged ; Aged ; *Environmental Exposure/statistics &amp; numerical data/adverse effects ; United Kingdom/epidemiology ; Prospective Studies ; *Air Pollution/statistics &amp; numerical data/adverse effects ; Particulate Matter/analysis ; *Eye Diseases/epidemiology ; *Macular Degeneration/epidemiology ; Cataract/epidemiology ; Glaucoma/epidemiology ; },
abstract = {OBJECTIVES: The associations between long-term joint exposure to low levels of multiple air pollutants and the incidence of common age-related eye diseases (AREDs), including cataract, glaucoma, and age-related macular degeneration (AMD), remain underexplored.<br><br>METHODS: We conducted a prospective cohort study using UK Biobank data from 441,567 participants without cataract, glaucoma, or AMD at baseline. An air pollution score was constructed to assess the combined effect of multiple air pollutants, including PM2.5, PM2.5-10, PM10, NO2 and NO. Cox proportional hazards models were used to evaluate associations.<br><br>RESULTS: Over a median follow-up of 14.41 years, 55,104 participants developed cataract, 11,940 glaucoma, and 9060 AMD. A relatively stronger association was observed between combined exposure to multiple pollutants and AREDs incidence compared to exposure to individual pollutants. For every interquartile range increase in the air pollution score, the risk of incident AREDs increased by 4-5&#x202f;% (cataract, HR [95&#x202f;% CI], 1.05 [1.04-1.06]; glaucoma, 1.04 [1.02, 1.06]; AMD, 1.04 [1.01, 1.07]), suggesting the potential additive or synergistic effects of exposure to pollutant mixtures. Compared to individuals in the lowest exposure quartile, those in the highest had a 13&#x202f;%, 9&#x202f;%, and 14&#x202f;% greater risk of developing cataract (1.13 [1.10-1.16]), glaucoma (1.09 [1.03-1.15]), and AMD (1.14 [1.07-1.22]), respectively.<br><br>CONCLUSIONS: Long-term joint exposure to multiple air pollutants, even at low concentrations, is associated with an increased risk of AREDs incidence, suggesting that reducing air pollution level could improve human ocular health. These findings provide a more comprehensive understanding of air pollution's impact on ocular health in the real world.},
}
@article {pmid40105475,
year = {2025},
author = {Lei, S and Liu, Y},
title = {Identifying microglia-derived NFKBIA as a potential contributor to the pathogenesis of Alzheimer's disease and age-related macular degeneration.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {105},
number = {1},
pages = {134-146},
doi = {10.1177/13872877251326267},
pmid = {40105475},
issn = {1875-8908},
mesh = {*Alzheimer Disease/genetics/metabolism/pathology ; Humans ; *Macular Degeneration/genetics/metabolism/pathology ; *Microglia/metabolism ; *NF-KappaB Inhibitor alpha/genetics/metabolism ; Gene Expression Profiling ; Protein Interaction Maps ; Transcriptome ; },
abstract = {BackgroundAlzheimer's disease (AD) and age-related macular degeneration (AMD) place considerable health burden on affected individuals and significant economic burden on society.ObjectiveThis study aims to explore the shared cellular and molecular mechanisms underlying the pathogenesis of AD and AMD.MethodsThe investigation in this study is conducted via single-cell and bulk tissue transcriptomic analysis. Transcriptomic datasets of AD and AMD were obtained from the GEO database. The shared differentially expressed genes (DEGs) in control and AD- and AMD-affected samples were identified. Functional enrichment analysis for DEGs was subsequently performed. Then, the protein-protein interaction (PPI) network of these DEGs was established via the STRING database and hub genes of this network were identified by Cytoscape software. Single-cell transcriptomic analysis was performed using Seurat R package to explore their expression in different cell types.ResultsDifferential analysis identified 127 shared DEGs of the two diseases, including 71 upregulated and 56 downregulated genes. Upregulated DEGs were enriched in inflammation, gliogenesis, cell apoptosis, and response to bacterial and viral infection and downregulated DEGs were enriched in mitochondrial function and energy production. PPI network and Cytoscape determined 10 hub genes, of which the NFKBIA gene was associated with the severity of both AD and AMD. Moreover, single-cell transcriptomic analysis showed that NFKBIA was highly expressed in microglia from disease-affected tissues.ConclusionsThe findings indicated that microglia with high NFKBIA expression were important contributors to the progression of both AD and AMD. Microglia-derived NFKBIA might serve as a potential therapeutic target for AD and AMD.},
}
@article {pmid40104816,
year = {2025},
author = {Davey, PG and Ranganathan, A},
title = {Editorial: Feast your eyes: diet and nutrition for optimal eye health.},
journal = {Frontiers in nutrition},
volume = {12},
number = {},
pages = {1579901},
pmid = {40104816},
issn = {2296-861X},
}
@article {pmid40102785,
year = {2025},
author = {Jeon, H and Yu, SY and Chertkova, O and Yun, H and Ng, YL and Lim, YY and Efimenko, I and Makhlouf, DM},
title = {Real-world insights of patient voices with age-related macular degeneration in the Republic of Korea and Taiwan: an AI-based Digital Listening study by Semantic-Natural Language Processing.},
journal = {BMC medical informatics and decision making},
volume = {25},
number = {1},
pages = {137},
pmid = {40102785},
issn = {1472-6947},
mesh = {Humans ; *Macular Degeneration/therapy ; Taiwan ; *Natural Language Processing ; Republic of Korea ; *Artificial Intelligence ; Semantics ; },
abstract = {BACKGROUND: In this era of active online communication, patients increasingly share their healthcare experiences, concerns, and needs across digital platforms. Leveraging these vast repositories of real-world information, Digital Listening enables the systematic collection and analysis of patient voices through advanced technologies. Semantic-NLP artificial intelligence, with its ability to process and extract meaningful insights from large volumes of unstructured online data, represents a novel approach for understanding patient perspectives. This study aimed to demonstrate the utility of Semantic-NLP technology in presenting the needs and concerns of patients with age-related macular degeneration (AMD) in Korea and Taiwan.<br><br>METHODS: Data were collected and analysed over three months from January 2023 using an ontology-based information extraction system (Semantic Hub). The system identified patient "stories" and extracted themes from online posts from January 2013 to March 2023, focusing on Korea and Taiwan by filtering the geographic location of users, the language used, and the local online platforms. Extracted texts were structured into knowledge graphs and analysed descriptively.<br><br>RESULTS: The patient voice was identified in 133,857 messages (9,620 patients) from the Naver online platform in Korea and included internet chat forums focused on macular degeneration. The most important factors for AMD treatments were effectiveness (1,632/3,401 mentions; 48%), price and access to insurance (33%), tolerability (10%) and doctor and clinic recommendations (9%). Treatment burden associated with intravitreal injection of vascular endothelial growth factor inhibitors related to tolerability (254/942 mentions; 27%), financial burden (20%), hospital selection (18%) and emotional burden (14%). In Taiwan, 444 messages were identified from Facebook, YouTube and Instagram. The success of treatment was judged by improvements in visual acuity (20/121 mentions; 16.5%), effect on oedema (10.7%), less distortion (9.1%) and inhibition of angiogenesis (5.8%). Tolerability concerns were rarely mentioned (26/440 mentions; 5.9%).<br><br>CONCLUSIONS: Digital Listening using Semantic-NLP can provide real-world insights from large amounts of internet data quickly and with low human labour cost. This allows healthcare companies to respond to the unmet needs of patients for effective and safe treatment and improved patient quality of life throughout the product lifecycle.},
}
@article {pmid40102632,
year = {2025},
author = {Salman, A and Song, WK and Storm, T and McClements, ME and MacLaren, RE},
title = {CRISPR targeting of SNPs associated with age-related macular degeneration in ARPE-19 cells: a potential model for manipulating the complement system.},
journal = {Gene therapy},
volume = {32},
number = {2},
pages = {132-141},
pmid = {40102632},
issn = {1476-5462},
mesh = {Humans ; *Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/therapy ; *CRISPR-Cas Systems ; Retinal Pigment Epithelium/metabolism/cytology ; Cell Line ; Gene Editing/methods ; *Complement System Proteins/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics ; Alleles ; Clustered Regularly Interspaced Short Palindromic Repeats ; },
abstract = {Age-related Macular degeneration (AMD) is a major cause of vision loss and is linked to several predisposing single nucleotide polymorphisms (SNPs). CRISPR-mediated genome editing offers the potential to target negatively associated SNPs in an allele-specific manner, necessitating the need for a relevant cell model. The ARPE-19 cell line, with its stable monolayer growth and retinal pigment epithelium (RPE) characteristics, serves as an ideal model for AMD studies. Chronic inflammation and complement system dysregulation are implicated in AMD pathogenesis. Most genetic variations associated with AMD are in complement genes, suggesting their regulatory role. In this study, we conducted targeted PCRs to identify AMD-related SNPs in ARPE-19 cells and used CRISPR constructs to assess allele-specific activity. Guide RNA sequences were cloned into an EF-1-driven SpCas9 vector and packaged into lentivirus. Targeting efficiencies were evaluated with TIDE analysis, and allele-specificity was measured with NGS analysis 30 days post-transduction. Our results showed varying targeting efficiencies depending on guide RNA efficacy. For example, TIDE analysis of CFH SNPs rs1061170 and rs1410996 revealed efficiencies of 35.5% and 33.8%, respectively. CFB SNP rs4541862 showed efficiencies from 3% to 36.7%, and rs641153 ranged from 3.4% to 23.8%. Additionally, allele-specific targeting of AMD-related SNPs rs1061170, rs1410996, rs4541862, and rs641153 ranged from 48% to 52% in heterozygous differentiated ARPE-19 cells. These findings demonstrate the potential to manipulate the complement system in an AMD model by targeting disease-associated SNPs in an allele-specific manner, offering a promising therapeutic approach.},
}
@article {pmid40102473,
year = {2025},
author = {Sumer, F and Subasi, S and Bahceci, I and Satilmaz, MF},
title = {Author Correction: Evaluation of serum galectin-3 concentration as a potential biomarker in exudative-type age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {9363},
doi = {10.1038/s41598-025-92480-0},
pmid = {40102473},
issn = {2045-2322},
}
@article {pmid40101366,
year = {2025},
author = {Ferroni, M and De Gaetano, F and Zonfrillo, M and Bono, N and Cereda, MG and Pierimarchi, P and Sferrazza, G and Candiani, G and Boschetti, F},
title = {Assessment of magnesium-based components for intraocular drug delivery byin vitrobiocompatibility and drug-device interaction.},
journal = {Biomedical materials (Bristol, England)},
volume = {20},
number = {3},
pages = {},
doi = {10.1088/1748-605X/adc21f},
pmid = {40101366},
issn = {1748-605X},
mesh = {*Magnesium/chemistry ; Animals ; Mice ; Rats ; Humans ; *Drug Delivery Systems/methods ; *Biocompatible Materials/chemistry ; Cell Survival/drug effects ; Bevacizumab/chemistry/administration &amp; dosage ; Cell Line ; Materials Testing ; Macular Degeneration/drug therapy ; 3T3 Cells ; Retinal Pigment Epithelium ; Drug Carriers/chemistry ; },
abstract = {The development of magnesium-based intraocular drug delivery devices holds significant promise for biomedical applications, particularly in treating wet age-related macular degeneration (AMD) using vascular endothelial growth factor inhibitors such as bevacizumab. Magnesium's rapid degradation, which can be finely tuned to achieve the controlled release required for AMD treatment, along with its well-established biocompatibility and biodegradable properties, positioning it as an ideal material for these applications. The study aimed to evaluate magnesium's potential as a carrier for ocular drug delivery systems by demontrating the stability of monoclonal antibodies, specifically bevacizumab, in the presence of magnesium corrosion products and the biocompatibility of these products with various cell lines, including murine fibroblasts (3T3), rat retinal Müller cells, and human retinal pigment epithelial cells (ARPE19). The stability of bevacizumab with pure magnesium (Mg) was investigated through an indirect enzyme-linked immunosorbent assay protocol, developed and customized for this specific aim. The biocompatibility of Mg corrosion products was assessed by toxicological evaluations through MTT and Trypan Blue Viability assays, along with cell cycle analysis. Results demonstrated no significant impact of Mg corrosion products on bevacizumab stability, with changes in mean values consistently below or equal to 10%. Furthermore, Mg extracts showed minimal cytotoxicity, as metabolic activity exceeded 80% across all cell lines, classified as Grade 0/1 cytotoxicity under ISO 10993-5 standards. Cell viability, proliferation, and morphology remained unaffected for up to 72 h of exposure. This study provides the firstin vitroevaluation of bevacizumab's stability in the presence of magnesium corrosion products and its biocompatibility with retinal cell lines, laying the foundation for future ophthalmic research and underscoring magnesium's potential as a material for intraocular drug delivery systems.},
}
@article {pmid40100494,
year = {2025},
author = {Singh, MK and Singh, L and Atilano, S and Chwa, M and Salimiaghdam, N and Kenney, MC},
title = {Retinal Pigment Epithelium and Monocytes' Mitochondrial Control of Ferroptosis and its Relevance to Age-Related Macular Degeneration.},
journal = {Molecular neurobiology},
volume = {62},
number = {7},
pages = {9306-9323},
pmid = {40100494},
issn = {1559-1182},
mesh = {*Ferroptosis/physiology ; Humans ; *Macular Degeneration/pathology/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Mitochondria/metabolism ; *Monocytes/metabolism/pathology ; Cell Line ; Cell Differentiation ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision impairment among older aged people. Recent studies have indicated that focusing on the underlying mechanism of ferroptosis (a form of iron-dependent cell death) could be crucial in understanding the progression of AMD, as it is strongly linked with inflammation. However, the specific dependence of ferroptosis on the mitochondria in the retinal pigment epithelium (RPE) and its surrounding immune cells remains unclear. In this study, we showed that mitochondria were required for the proliferation and maintenance of the RPE by regulating the expression of genes implicated in both pro- and antiferroptosis activities. Under chemically induced hypoxic conditions, Wt-ARPE-19 cells (basal mitochondrial level) increased the expression of genes linked with antiferroptotic activity. In contrast, rho0-ARPE-19 cells (mitochondria depleted) did not stimulate either pro- or antiferroptosis gene expression. However, diff-ARPE-19 cells (abundant in mitochondria) presented an improved proferroptotic activity. Furthermore, we demonstrated that mitochondria regulated monocyte differentiation into macrophages, resulting in differential expression of pro- and antiferroptotic factors. Through a direct coculture approach, the absence of mitochondria in ARPE-19 cells was shown to influences monocyte differentiation toward an inflammatory phenotype. This differentiation might increase ferroptosis activity. Transmitochondrial cybrids derived from patients with dry AMD and age-matched controls without dry AMD presented elevated mtDNA copy numbers, leading to increased ferritinophagy and increased levels of polyunsaturated fatty acids. These data highlighted that ferroptosis was partly regulated by mitochondria and that understanding the mechanisms governing the relationship between mitochondria and ferroptosis may open new potential avenues for managing dry AMD.},
}
@article {pmid40099236,
year = {2025},
author = {Garces, E and Slota, K and Stewart, MW and Guzman, MP and Werninck, NM and Castillo, PR},
title = {Age-Related Macular Degeneration and Circadian Preference.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {899-905},
pmid = {40099236},
issn = {1177-5467},
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness in developed nations. Within the retina, a subset of cells, called melanopsin-containing intrinsically photosensitive retinal ganglion cells, are implicated in circadian rhythms, prompting a search for a potential connection between circadian behavior and AMD. Our objective was to compare the chronotype (ie, preference for morning or evening activity) of individuals with AMD to that of those without ocular conditions.<br><br>PATIENTS AND METHODS: The Horne-&#xd6;stberg Morningness-Eveningness questionnaire was administered to previously screened patients with wet AMD who received bilateral anti-vascular endothelial growth factor eye injections (study participants) as well as those without eye pathology (controls). Thirty-one study participants and 19 controls completed the survey and were included in the analysis. We used Wilcoxon rank sum test and Fisher exact test for continuous and categorical variables respectively.<br><br>RESULTS: Study participants had a higher median age compared to controls (83 vs 75, P<0.001). No significant difference in body mass index was observed between respondents. While the disparity in survey responses between study participants and controls was generally not statistically significant, more study participants struggled with attending exercises between 7:00 and 8:00 in the morning compared to controls (45% vs 21%, P=0.02). Additionally, fewer study participants expressed the need to sleep before 10:15 pm compared to controls (55% vs 63%, P=0.04). Study participants tended to have a delayed sleep-wake cycle.<br><br>CONCLUSION: In this pilot study, study participants encountered greater challenges with morning exercise compared to controls. Nonetheless, there was no significant difference in chronotype between study participants and controls. The study could serve as a foundation for more extensive research exploring the interplay between vision loss and circadian rhythms.},
}
@article {pmid40098930,
year = {2025},
author = {Jobling, AI and Findlay, Q and Greferath, U and Vessey, KA and Gunnam, S and Morrison, V and Venables, G and Guymer, RH and Fletcher, EL},
title = {Nanosecond laser induces proliferation and improved cellular health within the retinal pigment epithelium.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1516900},
pmid = {40098930},
issn = {2296-858X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in those over 60 years of age. Although there are limited interventions that may prevent the development or progression of disease, more efficacious treatments are required. Short-pulsed laser treatment shows promise in delaying progression of early disease. This work details how nanosecond laser influences the retinal pigment epithelium (RPE), the principal cell type implicated in AMD.<br><br>METHODS: C57BL/6J mice (3-month-old) underwent monocular nanosecond laser treatment to assess short-term RPE response, while 9-month-old C57BL/6J and ApoEnull mice were similarly treated and longer-term responses investigated after 3&#x202f;months. Human tissue was also obtained after 2 nanosecond laser treatments (1&#x202f;month apart). RPE proliferation was assessed using bromodeoxyuridine and RPE gene change explored using qPCR and RNAseq. Melanin and lipofuscin content were quantified using histological techniques.<br><br>RESULTS: Nanosecond laser induced RPE proliferation in treated and fellow mouse eyes, with monolayer repair occurring within 3&#x202f;days. This was replicated in human tissue, albeit over a longer duration (1-4&#x202f;weeks). Wildtype animals showed no overt change in RPE gene expression after short or longer post-treatment durations, while laser treated ApoEnull animals showed increased Mertk and Pedf expression, and a reduced number of dysregulated aging genes in treated and fellow eyes after 3&#x202f;months. Furthermore, melanin and lipofuscin content were restored to wildtype levels in laser-treated ApoEnull RPE, while melanolipofuscin granules were reduced within treated regions of human RPE.<br><br>CONCLUSION: This work shows nanosecond laser stimulates RPE proliferation and results in an improved cellular phenotype. These data provide a biological basis for the prophylactic use of nanosecond lasers in AMD.},
}
@article {pmid40095326,
year = {2025},
author = {Fukuda, Y and Shiose, S and Notomi, S and Maehara, Y and Mori, K and Hashimoto, S and Kano, K and Ishikawa, K and Sonoda, KH},
title = {Two-year treatment outcomes after anti-vascular endothelial growth factor therapy in age-related macular degeneration with type 2 macular neovascularization in Japanese patients.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {3},
pages = {371-377},
pmid = {40095326},
issn = {1613-2246},
support = {JP21K09702//Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research/ ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Bevacizumab/administration &amp; dosage ; Fluorescein Angiography ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Japan/epidemiology ; *Macula Lutea/pathology ; *Ranibizumab/administration &amp; dosage ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/epidemiology ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) with type 2 macular neovascularization (MNV) has a relatively good responsiveness to anti-vascular endothelial growth factor (anti-VEGF) therapy compared to type 1 MNV. This study aimed to analyze the treatment outcomes of nAMD patients with type 2 MNV and identify factors associated with fluid recurrence.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: This study included treatment-na&#xef;ve nAMD patients with type 2 MNV but without type 1 MNV, who received 3-monthly anti-VEGF injections as the loading phase and were followed up for over 2 years. The treatment outcomes were compared between proactive (PA) and reactive regimen (RA) groups. In addition, we investigated the factors associated with fluid recurrence in the RA group.<br><br>RESULTS: This retrospective study included 65 eyes from 65 patients. Best-corrected visual acuity (BCVA) and central macular thickness significantly improved in both the PA and RA groups. Although there was no significant difference between the two groups, the RA group showed a trend towards better BCVA. The presence of fluid three or four months after the initial injection was associated with fluid recurrence in the RA group (p&#x2009;=&#x2009;0.02).<br><br>CONCLUSION: For nAMD patients with type 2 MNV, a proactive regimen is generally preferred. However, for nAMD patients with type 2 MNV achieving fluid resolution after the loading phase, it may be possible to maintain BCVA and reduce the number of anti-VEGF injections by following a reactive regimen.},
}
@article {pmid40094950,
year = {2025},
author = {Miyazato, M and Maruyama-Inoue, M and Tanaka, S and Inoue, T and Yanagi, Y and Kadonosono, K},
title = {Comparison Between Intravitreal Anti-Vascular Endothelial Growth Factor Monotherapy and Vitrectomy in Age-Related Macular Degeneration with Large Submacular Hemorrhages.},
journal = {Journal of clinical medicine},
volume = {14},
number = {5},
pages = {},
pmid = {40094950},
issn = {2077-0383},
abstract = {Objectives: To compare the 1-year visual outcomes of patients treated with intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy or vitrectomy for large submacular hemorrhages (SMHs) due to neovascular age-related macular degeneration (nAMD). Methods: We retrospectively studied 31 eyes with severe SMHs exceeding 3 disc areas (DAs) secondary to nAMD treated with anti-VEGF agents or a vitrectomy. Patients undergoing anti-VEGF monotherapy received three monthly loading doses of intravitreal injections of aflibercept or brolucizumab followed by as-needed injections or proactive treatment (anti-VEGF group); those undergoing vitrectomies underwent a 25-gauge vitrectomy and a submacular injection of tissue plasminogen activator (25 μg) and 0.4 mL of air with a microneedle having an outer diameter of 50 μm. The best-corrected visual acuities (BCVAs) were compared before and 6 and 12 months after initial treatment. Factors affecting the visual acuity (VA) at 12 months and VA improvements were determined. Results: A total of 17 eyes from 16 patients (54.8%) received anti-VEGF treatment and 14 eyes from 14 patients (45.2%) underwent vitrectomy. The baseline and 12-month mean logarithm of the minimum angle of resolution BCVAs in all eyes after treatment were 0.78 and 0.82, respectively, which were not significantly different (p = 0.661). The lens status, central foveal thickness (CFT) height, and baseline VA were associated significantly with the 12-month BCVA (p = 0.028, p = 0.008, and p = 0.021, respectively) and VA improvement (p = 0.015, p = 0.002, and p = 0.003, respectively). Conclusions: Anti-VEGF monotherapy and vitrectomy maintained functionality in patients with large SMHs due to nAMD. Greater CFT was associated with worse 12-month BCVA and less BCVA improvement despite the treatment modality.},
}
@article {pmid40094655,
year = {2025},
author = {Magagnoli, J and Cummings, T and Hardin, JW and Sutton, SS and Ambati, J},
title = {NLRP3 Activation With Bisphosphonate Use and the Risk of Incident Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {3},
pages = {32},
pmid = {40094655},
issn = {1552-5783},
support = {R01 AG078892/AG/NIA NIH HHS/United States ; R01 DA054992/DA/NIDA NIH HHS/United States ; R01 EY029799/EY/NEI NIH HHS/United States ; R01 EY031039/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Diphosphonates/adverse effects ; Incidence ; Aged ; *Macular Degeneration/epidemiology/chemically induced/metabolism ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists &amp; inhibitors ; *Bone Density Conservation Agents/adverse effects ; United States/epidemiology ; Risk Factors ; Middle Aged ; Absorptiometry, Photon ; Fluoxetine/therapeutic use ; Propensity Score ; Aged, 80 and over ; Inflammasomes/metabolism ; },
abstract = {PURPOSE: To determine whether bisphosphonate use increases the risk of age-related macular degeneration (AMD), thereby providing evidence for the involvement of the NLRP3 inflammasome in AMD pathogenesis.<br><br>METHODS: Retrospective cohort study among US veterans who had undergone dual-energy x-ray absorptiometry (DEXA) scans. Time-dependent Cox models were used to assess the association between cumulative bisphosphonate exposure and AMD incidence. Propensity score matching was applied to balance characteristics between bisphosphonate users and nonusers. A secondary analysis examined the impact of NLRP3 inhibitors (fluoxetine and fluvoxamine) on AMD risk among bisphosphonate users.<br><br>RESULTS: After propensity score matching, each additional year of bisphosphonate use was associated with a 4.7% increased hazard of AMD (hazard ratio [HR], 1.047; 95% confidence interval [CI], 1.020-1.074). In the secondary analysis, fluoxetine or fluvoxamine use among bisphosphonate users was linked to a reduced hazard of incident AMD (HR, 0.814; 95% CI, 0.676-0.98) in the matched sample.<br><br>CONCLUSIONS: Bisphosphonate use increases AMD risk, while NLRP3 inhibitors mitigate this effect. These findings support the hypothesis that the NLRP3 inflammasome is involved in AMD pathogenesis and represents a potential therapeutic target.},
}
@article {pmid40092741,
year = {2025},
author = {Wada, I and Oshima, Y and Fukuda, Y and Shiose, S and Kano, K and Ishikawa, K and Nakao, S and Kaizu, Y and Hasegawa, E and Kannan, R and Ishibashi, T and Sonoda, KH},
title = {Five-year Outcome of Aflibercept Administration with "Treat and Extend" for Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {835-845},
pmid = {40092741},
issn = {1177-5467},
abstract = {PURPOSE: This study aimed to evaluate the outcomes of aflibercept treatment using a treat-and-extend (TAE) regimen over up to 5 years in Japanese patients with neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This retrospective study included 126 consecutive treatment-na&#xef;ve nAMD patients (126 eyes) who received at least three monthly intravitreal aflibercept (IVA) injections as a loading phase, followed by a treat-and-extend (TAE) regimen with follow-up for 5 years. Injection intervals were adjusted every 2&#xa0;weeks and could be extended up to 16&#xa0;weeks based on macular condition. Treatment was suspended if patients received 3 injections at 16-week intervals and the macula remained dry (defined as "monitoring"). Ophthalmic exams were conducted at each visit to assess disease activity.<br><br>RESULTS: The mean logarithm of the minimum angle of resolution (logMAR) best corrected visual acuity (BCVA) at baseline was 0.42 &#xb1; 0.036. Following loading injections, the mean BCVA exhibited a significant improvement. Although it subsequently declined, it sustained the initial visual acuity. The average macular thickness (CMT) was significantly reduced and maintained throughout the follow-up period. The number of aflibercept injections decreased significantly from the second year and gradually decreased during the follow-up period. Intravitreal aflibercept (IVA) treatment could be discontinued in 36 (44%) cases during the follow-up period. However, 12 of these eyes (33%) experienced recurrence. Notably, significant recurrence was observed in patients who received a higher total number of aflibercept injections. Macular atrophy was significantly more likely to occur in cases with occult macular neovascularization (MNV) with subretinal hemorrhage than in cases with other forms of nAMD.<br><br>CONCLUSION: The long-term outcomes of IVA treatment utilizing TAE regimens for nAMD in real-world practice have demonstrated favorable results, including the maintenance of visual acuity and improvement in CMT over a 5-year period.},
}
@article {pmid40092639,
year = {2025},
author = {Poulsen, K and Hanna, K and Nieves, J and Nguyen, N and Sharma, P and Grishanin, R and Corbau, R and Kiss, S},
title = {Nonclinical study of ixo-vec gene therapy for nAMD supports efficacy for a human dose of 6E10 vg/eye and staggered dosing of fellow eyes.},
journal = {Molecular therapy. Methods &amp; clinical development},
volume = {33},
number = {1},
pages = {101430},
pmid = {40092639},
issn = {2329-0501},
abstract = {Ixoberogene soroparvovec (ixo-vec), formerly ADVM-022, is an adeno-associated virus (AAV) gene therapy using the AAV.7m8 capsid for intravitreal delivery (IVT) to transduce retinal tissue and produce sustained intraocular aflibercept for treating neovascular age-related macular degeneration (nAMD). Non-clinical studies show that aflibercept production by ixo-vec is less than dose proportional, while intraocular inflammation (IOI) increases with dose, suggesting that lower doses could yield effective aflibercept levels with reduced IOI risk. Our evaluation confirmed that doses as low as 3E10 vg (vector genome)/eye (6E10 vg/eye human equivalent) maintained effective aflibercept production. The concept behind ADVM-022 is supported by clinical studies OPTIC (NCT03748784) and LUNA (NCT05536973), where a single IVT administration eliminated or significantly reduced the need for additional anti-VEGF injections in patients. Moreover, LUNA confirmed the clinical efficacy of a 6E10-vg/eye dose, demonstrating robust and sustained aflibercept levels. Additionally, we evaluated staggered dosing in contralateral eyes to treat asynchronous disease development. Staggered dosing, administered 2 months apart, did not exacerbate IOI, and both eyes maintained therapeutic aflibercept levels. These findings support the tolerability and efficacy of staggered dosing, indicating the potential for bilaterally relevant aflibercept levels with ixo-vec, due to immune response confinement to the dosed eye.},
}
@article {pmid40091912,
year = {2025},
author = {Mukherjee, S and De Silva, T and Duic, C and Jayakar, G and Keenan, TDL and Thavikulwat, AT and Chew, E and Cukras, C},
title = {Validation of Deep Learning-Based Automatic Retinal Layer Segmentation Algorithms for Age-Related Macular Degeneration with 2 Spectral-Domain OCT Devices.},
journal = {Ophthalmology science},
volume = {5},
number = {3},
pages = {100670},
pmid = {40091912},
issn = {2666-9145},
abstract = {PURPOSE: Segmentations of retinal layers in spectral-domain OCT (SD-OCT) images serve as a crucial tool for identifying and analyzing the progression of various retinal diseases, encompassing a broad spectrum of abnormalities associated with age-related macular degeneration (AMD). The training of deep learning algorithms necessitates well-defined ground truth labels, validated by experts, to delineate boundaries accurately. However, this resource-intensive process has constrained the widespread application of such algorithms across diverse OCT devices. This work validates deep learning image segmentation models across multiple OCT devices by testing robustness in generating clinically relevant metrics.<br><br>DESIGN: Prospective comparative study.<br><br>PARTICIPANTS: Adults >50 years of age with no AMD to advanced AMD, as defined in the Age-Related Eye Disease Study, in &#x2265;1 eye, were enrolled. Four hundred two SD-OCT scans were used in this study.<br><br>METHODS: We evaluate 2 separate state-of-the-art segmentation algorithms through a training process using images obtained from 1 OCT device (Heidelberg-Spectralis) and subsequent testing using images acquired from 2 OCT devices (Heidelberg-Spectralis and Zeiss-Cirrus). This assessment is performed on a dataset that encompasses a range of retinal pathologies, spanning from disease-free conditions to severe forms of AMD, with a focus on evaluating the device independence of the algorithms.<br><br>MAIN OUTCOME MEASURES: Performance metrics (including mean squared error, mean absolute error [MAE], and Dice coefficients) for the segmentations of the internal limiting membrane (ILM), retinal pigment epithelium (RPE), and RPE to Bruch's membrane region, along with en face thickness maps, volumetric estimations (in mm[3]). Violin plots and Bland-Altman plots comparing predictions against ground truth are also presented.<br><br>RESULTS: The UNet and DeepLabv3, trained on Spectralis B-scans, demonstrate clinically useful outcomes when applied to Cirrus test B-scans. Review of the Cirrus test data by 2 independent annotators revealed that the aggregated MAE in pixels for ILM was 1.82&#xa0;&#xb1;&#xa0;0.24 (equivalent to 7.0&#xa0;&#xb1;&#xa0;0.9 &#x3bc;m) and for RPE was 2.46&#xa0;&#xb1;&#xa0;0.66 (9.5&#xa0;&#xb1;&#xa0;2.6 &#x3bc;m). Additionally, the Dice similarity coefficient for the RPE drusen complex region, comparing predictions to ground truth, reached 0.87&#xa0;&#xb1;&#xa0;0.01.<br><br>CONCLUSIONS: In the pursuit of task-specific goals such as retinal layer segmentation, a segmentation network has the capacity to acquire domain-independent features from a large training dataset. This enables the utilization of the network to execute tasks in domains where ground truth is hard to generate.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40091366,
year = {2025},
author = {Sutinen, P and Jeon, S and Kanclerz, P and Tuuminen, R},
title = {Correlation between aqueous flare levels and anti-VEGF treatment response in wet age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {35},
number = {5},
pages = {1686-1694},
doi = {10.1177/11206721251327648},
pmid = {40091366},
issn = {1724-6016},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Aqueous Humor/metabolism ; Male ; Female ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; Aged ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Visual Acuity/physiology ; Aged, 80 and over ; Tomography, Optical Coherence ; Bevacizumab/administration &amp; dosage ; Fluorescein Angiography ; Treatment Outcome ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor ; },
abstract = {PurposeTo analyze the association between aqueous flare and wet age-related macular degeneration (AMD) activity during anti-VEGF treatment using the treat-and-extend (T&amp;E) protocol.MethodsA single-centre study consisting of 84 eyes of 84 patients with wet AMD and 17 eyes of 17 patients with dry AMD at Ophthalmology Unit, Mehiläinen Hospital, Helsinki, Finland. Aqueous flare levels were recorded with a laser flare meter. Inclusion criteria was a minimum of six anti-VEGF doses given before enrollment to the study.ResultsAqueous flare levels inversely correlated with the anti-VEGF treatment interval (R[2 ]= 0.16, P < 0.001). In the group with a 4-6-week treatment interval the aqueous flare was 13.6 ± 8.3 photon units (pu)/ms compared to 7.9 ± 2.9 pu/ms (P = 0.008), 7.8 ± 3.5 pu/ms (P = 0.006), and 7.2 ± 3.8 pu/ms (P = 0.002) among patients with 7-9-week, 10-12-week, and 13-16-week intervals, respectively. Aqueous flare was 15.4 ± 8.5 pu/ms in the group whose treatment intervals were shortened, compared to 8.6 ± 3.8 pu/ms (P = 0.003) and 7.3 ± 3.3 pu/ms (P < 0.001) in the groups where the treatment intervals were maintained or extended, respectively. Furthermore, aqueous flare levels correlated with the macular volume (R[2 ]= 0.07, P = 0.018). Regarding macular activity, the presence of intraretinal fluid associated with higher aqueous flare levels (13.8 ± 8.6 pu/ms) compared to those without it (8.0 ± 4.0 pu/ms; P < 0.001). Patient age, pseudophakia or the anti-VEGF agent did not associate with the aqueous flare levels.ConclusionsAqueous flare measurements correlated with wet AMD activity during anti-VEGF treatment. Aqueous flare could be used to help evaluate the state of wet AMD patients and assist in decisions regarding anti-VEGF treatment modifications.},
}
@article {pmid40090700,
year = {2025},
author = {Kang, HM and Mendez, KM and Laíns, I and Sourirajan, K and Bhat, R and Nigalye, A and Katz, R and Kozak, G and Choi, H and Bannerman, A and Alvarez, RA and Wu, D and Kim, IK and Liang, L and Miller, JB and Vavvas, DG and Miller, JW and Lasky-Su, J and Husain, D},
title = {Association of plasma metabolites with treatment response after intravitreal anti-vascular endothelial growth factor injections in treatment-naïve neovascular age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {40090700},
issn = {2397-3269},
support = {R01 EY030088/EY/NEI NIH HHS/United States ; R01 HL123915/HL/NHLBI NIH HHS/United States ; R01 HL141826/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Prospective Studies ; Tomography, Optical Coherence/methods ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Wet Macular Degeneration/drug therapy/blood/diagnosis ; *Ranibizumab/administration &amp; dosage ; Biomarkers/blood ; *Bevacizumab/administration &amp; dosage ; *Visual Acuity ; Treatment Outcome ; Aged, 80 and over ; Follow-Up Studies ; Metabolomics ; Fluorescein Angiography ; },
abstract = {BACKGROUND/AIMS: To investigate the association between plasma metabolomic profiles and treatment response after intravitreal anti-vascular endothelial growth factor (VEGF) injections in treatment-naïve neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This is part of a prospective longitudinal study that included patients with treatment-na&#xef;ve nAMD who have undergone three loading intravitreal anti-VEGF injections. All patients underwent ophthalmological examinations including spectral domain optical coherence tomography (SD OCT). Fasting blood samples were collected at the time of study enrolment (not to first anti-VEGF injection) and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry. Treatment response was defined as no evidence of any subretinal and intraretinal fluid on SD OCT 4-6 weeks after the third injection. Multilevel mixed-effects linear modelling was used to assess associations between plasma metabolites and treatment response. Multiple comparisons were accounted for using the effective number of tests to explain 80% of the variance (ENT80), with a p value threshold of 0.0017.<br><br>RESULTS: We included 131 eyes of 101 patients, and 69 patients (68.3%) were female. 51 eyes (38.9%) were treatment responders. Taurodeoxycholate (TDCA) was the only plasma metabolite significantly associated with treatment response (&#x3b2;=1.6, ENT80=0.001).<br><br>CONCLUSION: In our study, TDCA was the most significant plasma metabolite associated with treatment response after three-loading dose of anti-VEGF therapy in patients with nAMD. Bile acids may have a beneficial impact on treatment response in nAMD through their neuroprotective property. Plasma metabolites may be used as biomarkers to predict responses to initial anti-VEGF therapy in patients with nAMD, providing a more individualised treatment plan.},
}
@article {pmid40090458,
year = {2025},
author = {Purdy, R and John, M and Bray, A and Clare, AJ and Copland, DA and Chan, YK and Henderson, RH and Nerinckx, F and Leroy, BP and Yang, P and Pennesi, ME and MacLaren, RE and Fischer, MD and Dick, AD and Xue, K},
title = {Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy.},
journal = {Progress in retinal and eye research},
volume = {106},
number = {},
pages = {101354},
doi = {10.1016/j.preteyeres.2025.101354},
pmid = {40090458},
issn = {1873-1635},
mesh = {Humans ; *Genetic Therapy/adverse effects/methods ; *Uveitis/etiology/immunology ; Genetic Vectors ; Dependovirus/genetics ; *Retinal Diseases/therapy ; Animals ; },
abstract = {Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common retinal diseases such as age-related macular degeneration and diabetic retinopathy. The delivery and expression of therapeutic transgenes in the eye is limited by innate and adaptive immune responses against components of the vector product, which has been termed gene therapy-associated uveitis (GTAU). This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment. For retinal gene therapy to achieve an improved efficacy and safety profile for treating additional IRDs and more common diseases, the risk of GTAU must be minimised. We have collated insights from pre-clinical research, clinical trials, and the real-world implementation of AAV-mediated retinal gene therapy to help understand the risk factors for GTAU. We draw attention to an emerging framework, which includes patient demographics, vector construct, vector dose, route of administration, and choice of immunosuppression regime. Importantly, we consider efforts to date and potential future strategies to mitigate the adverse immune response across each of these domains. We advocate for more targeted immunomodulatory approaches to the prevention and treatment of GTAU based on better understanding of the underlying immune response.},
}
@article {pmid40089957,
year = {2025},
author = {Chen, KY and Lee, HK and Chan, HC and Chan, CM},
title = {Is Multiwavelength Photobiomodulation Effective and Safe for Age-Related Macular Degeneration? A Systematic Review and Meta-Analysis.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {5},
pages = {969-987},
pmid = {40089957},
issn = {2193-8245},
abstract = {INTRODUCTION: This systematic review and meta-analysis compares the complications and effects of photobiomodulation (PBM) therapy with sham treatment in patients with age-related macular degeneration (AMD). AMD is a leading cause of visual impairment in older adults, with current treatments primarily focusing on symptom management. PBM therapy is emerging as a potential intervention to improve clinical and anatomical outcomes in patients with AMD, necessitating a comparative analysis with sham treatment to determine its efficacy and safety.<br><br>METHODS: A systematic search was conducted across PubMed/Medline, Google Scholar and the Cochrane Library from inception to January 13, 2025. Randomised controlled trials (RCTs) meeting predefined inclusion criteria were selected. Meta-analysis employed random-effects models. The risk of bias in the included studies was assessed using Cochrane tools.<br><br>RESULTS: A total of six studies, comprising 360 patients and 477 eyes, focused on PBM for dry AMD. Five studies were eligible for meta-analysis. Best-corrected visual acuity (BCVA) showed no significant improvement with PBM (SMD -&#x2009;0.30, 95%&#xa0;CI -&#x2009;0.85 to 0.26, p&#x2009;=&#x2009;0.30), with high heterogeneity (I[2]&#x2009;=&#x2009;83%). Macular drusen volume also showed no significant change (SMD -&#x2009;0.08, 95%&#xa0;CI -&#x2009;0.52 to 0.37, p&#x2009;=&#x2009;0.74), with moderate heterogeneity (I[2]&#x2009;=&#x2009;48%). A single study reported no significant effect on geographic atrophy (SMD -&#x2009;0.28, 95%&#xa0;CI -&#x2009;1.26 to 0.71, p&#x2009;=&#x2009;0.58). Central subfield thickness (SMD 0.11, 95%&#xa0;CI -&#x2009;0.25 to 0.47, p&#x2009;=&#x2009;0.58) and microperimetry (SMD -&#x2009;0.02, 95%&#xa0;CI -&#x2009;0.48 to 0.44, p&#x2009;=&#x2009;0.94) also showed no significant changes. The adverse events analysis indicated a statistically significant increase in adverse events in the sham group within 6&#xa0;months (RR 0.48, 95%&#xa0;CI 0.29-0.82, p&#x2009;=&#x2009;0.007), while the overall effect on adverse events was non-significant (RR 1.04, 95%&#xa0;CI 0.51-2.12, p&#x2009;=&#x2009;0.91, I[2]&#x2009;=&#x2009;78%). Qualitative analysis suggested that PBM might enhance quality of life and clinical and anatomical outcomes compared to sham treatment.<br><br>CONCLUSION: This meta-analysis suggests that, to date, there are no significant clinical benefits of PBM therapy for patients with AMD. Further long-term studies are needed to establish its clinical relevance and safety profile.},
}
@article {pmid40089567,
year = {2025},
author = {Lee, J and Choi, J and Yu, SY and Kim, K},
title = {Recurrence of neovascular age-related macular degeneration after discontinuation of modified treat and extend treatment.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8952},
pmid = {40089567},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; Aged ; Recurrence ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy ; Risk Factors ; Ranibizumab/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Middle Aged ; Treatment Outcome ; },
abstract = {We evaluated the incidence and risk factors for recurrence in patients with neovascular age-related macular degeneration (nAMD) who discontinued anti-vascular endothelial growth factor (VEGF) therapy under a modified treat-and-extend (TAE) protocol. A retrospective analysis of 68 patients was conducted. Therapy was discontinued after extending the treatment interval to ≥ 5 months and maintaining disease stability for 6 months. The modified TAE protocol included three phases: loading, observation, and TAE, with initial treatment intervals determined by the first recurrence interval. Recurrence rates were 22.2%, 42.2%, and 54.4% at 1-, 2-, and 3-year follow-ups, respectively. The median time to recurrence was 16 months, with patients receiving an average of 7.7 injections before discontinuation. Intraretinal cysts were significantly more prevalent in patients with recurrence. Rapid early response to treatment was associated with a lower risk of exudative recurrence. Vision loss of two or more lines occurred in five patients despite treatment resumption; all exhibited subretinal hemorrhages on baseline imaging. The modified TAE protocol allows for successful therapy discontinuation with fewer injections and reduced recurrence rates. Patients with a favorable early response to anti-VEGF therapy had a lower risk of recurrence.},
}
@article {pmid40089174,
year = {2025},
author = {Eichenbaum, DA and Holekamp, N and Khanani, AM and Pieramici, D and Hershberger, V and Sheth, V and Brunstein, F and Ma, L and Zou, Y and Indjeian, VB and Dere, R and Maia, M and Hsu, JC and Gao, SS and Yaspan, B and Willis, JR and Wiley, H and Lai, P and Chen, H},
title = {Phase 2 Study of the Anti-High Temperature Requirement A1 (HtrA1) Fab Galegenimab (FHTR2163) in Geographic Atrophy Secondary to Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {275},
number = {},
pages = {14-26},
doi = {10.1016/j.ajo.2025.03.021},
pmid = {40089174},
issn = {1879-1891},
mesh = {Humans ; Male ; *Geographic Atrophy/drug therapy/etiology/diagnosis/physiopathology ; Female ; Intravitreal Injections ; Aged ; Visual Acuity/physiology ; *High-Temperature Requirement A Serine Peptidase 1/antagonists &amp; inhibitors ; Single-Blind Method ; Fluorescein Angiography ; Aged, 80 and over ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Tomography, Optical Coherence ; *Immunoglobulin Fab Fragments/therapeutic use ; Treatment Outcome ; *Macular Degeneration/complications/drug therapy ; Middle Aged ; },
abstract = {PURPOSE: To investigate the safety, tolerability, and efficacy of intravitreal injection of galegenimab, an anti-HtrA1 FAb, in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>DESIGN: Phase 2, single-masked, randomized clinical trial.<br><br>METHODS: Eligible GA patients with BCVA letter scores of &#x2265; 24 letters and baseline GA lesion size 2.54&#x223c;25.4 mm[2] in the study eye were enrolled. Patients were randomized 2:1:2 to receive 20 mg galegenimab every 4 (Q4W) or 8 weeks (Q8W), or sham Q4/8 W. The primary endpoint was mean change in GA area from baseline to Week 72 measured by fundus autofluorescence. A data monitoring committee (DMC) conducted periodic unmasked review of cumulative safety/limited efficacy data of the ongoing study.<br><br>RESULTS: Among 337 patients who received &#x2265; 1 dose and have at least one postbaseline GA area measurement, the adjusted mean change in GA area from baseline to Week 72 was 2.67, 2.50, and 2.38 mm[2] for the galegenimab Q4W, galegenimab Q8W, and pooled sham arms, respectively. Differences between the treated and sham groups were not statistically significant. However, the rate of intraocular inflammation was high (7.1%, 16/224 patients) among treated patients. The DMC recommended early termination of the study based on an early benefit/risk analysis.<br><br>CONCLUSION: Galegenimab administration did not show a difference in mean change in GA area from baseline to Week 72 compared with sham. Inhibition of HtrA1 with a Fab did not slow down GA progression.},
}
@article {pmid40089136,
year = {2025},
author = {Ratnapriya, R and Grassman, F and Chen, R and Hewitt, A and Du, J and Saban, DR and Klaver, CCW and Ash, J and Stambolian, D and Tumminia, SJ and Qian, J and Husain, D and Iyengar, SK and den Hollander, AI},
title = {Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms.},
journal = {Experimental eye research},
volume = {254},
number = {},
pages = {110344},
pmid = {40089136},
issn = {1096-0007},
support = {R01 EY034364/EY/NEI NIH HHS/United States ; P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY030088/EY/NEI NIH HHS/United States ; R01 EY030906/EY/NEI NIH HHS/United States ; R01 EY031324/EY/NEI NIH HHS/United States ; R01 EY032462/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/genetics ; *Genomics/methods ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; },
abstract = {Genome-wide association studies have been remarkably successful in identifying genetic variants associated with age-related macular degeneration (AMD), demonstrating a strong genetic component largely driven by common variants. However, progress in translating these genetic findings into a deeper understanding of disease mechanisms and new therapies has been slow. Slow progress in this area can be attributed to limited knowledge of the functional impact of AMD-associated non-coding variants on gene function, the molecular mechanisms and cell types underlying disease. This review offers a comprehensive overview of functional genomics approaches to uncover the genetic, epigenetic, cellular and molecular mechanisms underlying AMD and outlines future directions for research.},
}
@article {pmid40089134,
year = {2025},
author = {Gim, N and Ferguson, A and Blazes, M and Soundarajan, S and Gasimova, A and Jiang, Y and Sánchez, CI and Zalunardo, L and Corradetti, G and Elze, T and Honda, N and Waheed, NK and Cairns, AM and Canto-Soler, MV and Domalpally, A and Durbin, M and Ferrara, D and Hu, J and Nair, P and Lee, AY and Sadda, SR and Keenan, TDL and Patel, B and Lee, CS and , },
title = {Publicly available imaging datasets for age-related macular degeneration: Evaluation according to the Findable, Accessible, Interoperable, Reusable (FAIR) principles.},
journal = {Experimental eye research},
volume = {255},
number = {},
pages = {110342},
pmid = {40089134},
issn = {1096-0007},
support = {OT2 OD032644/OD/NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Tomography, Optical Coherence/methods ; *Databases, Factual ; Machine Learning ; Artificial Intelligence ; *Information Dissemination ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss among older adults, affecting more than 200 million people worldwide. With no cure currently available and a rapidly increasing prevalence, emerging approaches such as artificial intelligence (AI) and machine learning (ML) hold promise for advancing the study of AMD. The effective utilization of AI and ML in AMD research is highly dependent on access to high-quality and reusable clinical data. The Findable, Accessible, Interoperable, Reusable (FAIR) principles, published in 2016, provide a framework for sharing data that is easily useable by both humans and machines. However, it is unclear how these principles are implemented with regards to ophthalmic imaging datasets for AMD research. We evaluated openly available AMD-related datasets containing optical coherence tomography (OCT) data against the FAIR principles. The assessment revealed that none of the datasets were fully compliant with FAIR principles. Specifically, compliance rates were 5 % for Findable, 82 % for Accessible, 73 % for Interoperable, and 0 % for Reusable. The low compliance rates can be attributed to the relatively recent emergence of these principles and the lack of established standards for data and metadata formatting in the AMD research community. This article presents our findings and offers guidelines for adopting FAIR practices to enhance data sharing in AMD research.},
}
@article {pmid40089029,
year = {2025},
author = {Chen, Y and Jiang, F and Zeng, Y and Zhang, M},
title = {The role of retinal pigment epithelial senescence and the potential of senotherapeutics in age-related macular degeneration.},
journal = {Survey of ophthalmology},
volume = {70},
number = {5},
pages = {942-950},
doi = {10.1016/j.survophthal.2025.03.004},
pmid = {40089029},
issn = {1879-3304},
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/drug effects ; *Macular Degeneration/drug therapy/physiopathology/pathology ; *Cellular Senescence/physiology ; *Senotherapeutics/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment in the aging population. Evidence showing the presence of cellular senescence in retinal pigment epithelium (RPE) of patients with AMD is growing. Senescent RPE play a pivotal role in its pathogenesis. The senescent RPE suffers from structural and functional alterations and disruption of the surrounding microenvironment due to the development of the senescence-associated secretory phenotype, which contributes to metabolic dysfunctions and inflammatory responses in the retina. Senotherapeutics, including senolytics, senomorphics and others, are novel treatments targeting senescent cells and are promising treatments for AMD. As senotherapeutic targets are being developed, it is promising that the burden of AMD could be decreased.},
}
@article {pmid40087500,
year = {2025},
author = {Lim, G and Kim, KT and Kim, DY and Chae, JB and Seo, EJ},
title = {Early optical coherence tomography biomarkers for tailored frequency of intravitreal aflibercept in neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8911},
pmid = {40087500},
issn = {2045-2322},
support = {RS-2024-00340391//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Male ; Female ; Intravitreal Injections ; Aged ; Retrospective Studies ; Biomarkers ; *Macular Degeneration/drug therapy/diagnostic imaging ; Aged, 80 and over ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Visual Acuity/drug effects ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; },
abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) injections are essential for treating neovascular age-related macular degeneration (nAMD), but patient responses vary significantly, complicating standardized regimens. This study identifies early optical coherence tomography (OCT) biomarkers and best-corrected visual acuity (BCVA) as predictors of injection frequency in a one-year treat-and-extend (T&amp;E) regimen to optimize individualized treatment. A retrospective analysis of treatment-naïve nAMD patients receiving intravitreal aflibercept was conducted. Patients underwent three initial monthly loading injections, followed by a modified T&amp;E regimen. OCT parameters and BCVA were assessed at baseline, during, and after the loading phase to identify associations with injection frequency and recurrence intervals. Post-loading central subfield thickness (CST) significantly predicted injection frequency (p < 0.001) and recurrence timing (p = 0.013), while baseline CST and BCVA showed no correlation. BCVA remained similar between high- and low-treatment-need groups despite differing injection frequencies. Type 2 macular neovascularization responded more rapidly to treatment than type 1, reflecting varying dynamics. CST after the loading phase is a reliable predictor of treatment needs within one year, superior to baseline biomarkers. Early response monitoring during loading enables personalized anti-VEGF therapy, minimizing overtreatment and preserving vision, underscoring the value of individualized management in nAMD.},
}
@article {pmid40085312,
year = {2025},
author = {Küçük, E and Çoban Karataş, M},
title = {Comparison of choroidal thickness and vascularity in patients with subretinal drusenoid deposits and large drusen using swept-source optical coherence tomography.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {94},
pmid = {40085312},
issn = {1573-2630},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/pathology/blood supply/diagnostic imaging ; *Retinal Drusen/diagnosis ; Male ; Female ; Aged ; Middle Aged ; Fluorescein Angiography/methods ; Fundus Oculi ; Aged, 80 and over ; *Retinal Vessels/pathology ; *Macular Degeneration/diagnosis ; Visual Acuity ; Retrospective Studies ; },
abstract = {PURPOSE: The aim of this study is to assess the choroidal features in patients diagnosed with non-advanced age-related macular degeneration (AMD) using Swept-source Optical Coherence Tomography (SS-OCT) and compare the findings of those with subretinal drusenoid deposits (SDD) and those with large drusen.<br><br>METHODS: Individuals aged 50&#xa0;years and above, presenting with either SDD or large drusen alongside non-advanced AMD, underwent a thorough ophthalmic assessment. OCT scans were acquired using SS-OCT. Choroidal thickness (CT) maps within the early treatment diabetic retinopathy study (ETDRS) subfields were obtained. Choroidal vascularity index (CVI) was obtained from a foveal horizontal OCT scan, and it was determined as the ratio of luminal area to the total choroidal area. The data obtained were compared between the groups.<br><br>RESULTS: Forty-three eyes of 27 patients with SDD and 40 eyes of 21 patients with large drusen were included in the study. The mean age was 72.0&#x2009;&#xb1;&#x2009;8.6&#xa0;years in the SDD group and 71.3&#x2009;&#xb1;&#x2009;5.6&#xa0;years in the large drusen group with no significant difference (p&#x2009;=&#x2009;0.717). In the choroidal thickness maps CT and CT in all ETDRS subfields were significantly lower in SDD group compared to the large drusen group. CVI values were not significantly different between SDD (0.628&#x2009;&#xb1;&#x2009;0.18) and large drusen groups (0.629&#x2009;&#xb1;&#x2009;0.20) (p&#x2009;=&#x2009;0.812).<br><br>CONCLUSION: Non-advanced AMD patients with SDD exhibited reduced choroidal thickness compared to those with large drusen. Choroidal vascularity index did not significantly differ, suggesting that choroidal thickness may play a more substantial role than vascularity changes in the pathogenesis of SDD.},
}
@article {pmid40085093,
year = {2025},
author = {Hanna, J and Markle, J and Maatouk, C and Das, N and Talcott, KE and Singh, RP},
title = {Predictors of Visual Response After Lapse in Treatment Among Patients With Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {5},
pages = {280-285},
doi = {10.3928/23258160-20250128-01},
pmid = {40085093},
issn = {2325-8179},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; *Ranibizumab/administration &amp; dosage ; Follow-Up Studies ; Middle Aged ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Bevacizumab/administration &amp; dosage ; Fundus Oculi ; },
abstract = {BACKGROUND AND OBJECTIVE: This study aimed to analyze baseline predictors of visual response in patients with neovascular age-related macular degeneration (nAMD) who have undergone lapses in treatment with anti-VEGF therapy. The mainstay treatment option for nAMD is intravitreal vascular endothelial growth factor inhibitor (anti-VEGF) therapy. Given the chronic nature of nAMD, patients who undergo lapses in treatment with these agents can have progression of their disease.<br><br>PATIENTS AND METHODS: This retrospective, comprehensive chart review included 261 adults aged 18 years or older who were diagnosed with nAMD between January 2012 and June 2020 and had undergone at least one anti-VEGF injection prior to an unintended lapse in follow-up of 3 months or greater. Following exclusion criteria, in which individuals were not administered an anti-VEGF injection at the pre-lapse visit, a total of 163 patients were analyzed. Patients were separated into "vision loss" and "stable vision" categories and classified based on degree of vision loss. A stepwise backward logistic regression was used to analyze baseline medical and ophthalmic factors between each group to determine which factors were more likely to be associated with more significant vision loss.<br><br>RESULTS: Out of 261 nAMD patients reviewed, 163 patients were investigated in the main analysis. Higher cube volume (1.24 &#xb1; 0.24, P = 0.22), and lapse length (2.89 &#xb1; 0.056, P = 0.004) increased the likelihood of vision loss, while lack of smoking history (-2.07 &#xb1; 0.46, P = 0.038) decreased the likelihood. The two groups were significantly different in post-lapse ophthalmologic continuous variables, including cube volume (9.69 &#xb1; 0.98 and 10.2 &#xb1; 1.39 in the stable vision and unstable vision groups, respectively, P = 0.01) and cube average thickness (269 &#xb1; 27.3 and 282 &#xb1; 38.4 in the stable vision and unstable vision groups, respectively, P = 0.02). The main model had an area under the curve (AUC) of 58% and predictive accuracy of 78.1%.<br><br>CONCLUSION: The calculated AUC was not high enough to establish reliable predictability in this study. However, additional factors may need to be considered for greater predictability. [Ophthalmic Surg Lasers Imaging Retina 2025;56:280-285.].},
}
@article {pmid40083923,
year = {2025},
author = {Zhang, YR and Li, WQ and Zhang, ZH and Sun, RX and Zhu, HJ and Qian, HM and Yuan, ST and Wang, YL},
title = {YBX1-driven TUBB6 upregulation facilitates ocular angiogenesis via WNT3A-FZD8 pathway.},
journal = {Theranostics},
volume = {15},
number = {7},
pages = {2680-2699},
pmid = {40083923},
issn = {1838-7640},
mesh = {Animals ; Mice ; *Choroidal Neovascularization/metabolism/genetics/pathology ; Humans ; *Tubulin/metabolism/genetics ; Up-Regulation ; Endothelial Cells/metabolism ; Disease Models, Animal ; Mice, Knockout ; Diabetic Retinopathy/metabolism/pathology/genetics ; *Frizzled Receptors/metabolism ; Mice, Inbred C57BL ; *Retinal Neovascularization/metabolism/genetics ; Retina/metabolism ; Cell Proliferation ; Signal Transduction ; Wnt Signaling Pathway ; *Neovascularization, Pathologic/metabolism/genetics ; Angiogenesis ; },
abstract = {Background: Pathological ocular neovascularization, a characteristic feature of proliferative ocular diseases, is a primary contributor to global vision impairment. The dynamics of tubulin are crucial in maintaining ocular homeostasis, closely linked to cellular proliferation and angiogenesis. Elucidating the molecular mechanisms driving this process is vital for formulating effective therapeutic strategies. Methods: Multiple transcriptome analyses revealed upregulation of endothelial tubulin beta-6 chain (Tubb6) in oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) mice models. Transwell migration assay, wound healing assay, tube formation assay, flow cytometry, and immunofluorescent staining were employed to identify the role of TUBB6 knockout (KO) in vitro. The effects of Tubb6 silencing on retinal angiogenesis and choroidal neovascularization were subsequently evaluated. Results: We identified upregulated Tubb6 expression in retinas from OIR mice through combination analyses of single-cell RNA sequencing (scRNA-Seq) and bulk RNA-Seq. The RNA expression profiles of endothelial cells (ECs) from proliferative diabetic retinopathy (PDR) patients and neovascular age-related macular degeneration (nAMD) patients also exhibited an elevation in TUBB6. Notably, Tubb6 was abundantly expressed in ECs and pericytes, and was predominantly localized to proliferative ECs and vascular tip cells. Functional studies demonstrated that TUBB6 knockdown reduced the expression of proliferative and tip cell markers in vitro. Tubb6 deficiency decreased vascular sprouting and tip cell formation of OIR mice retina and retarded CNV progression in vivo. Mechanistically, YBX1, an RNA-binding protein, was identified as an upstream regulator of TUBB6 via binding to its 3' untranslated region (3'UTR) and maintaining mRNA stability. Transcriptome analysis further linked TUBB6 to the activity of WNT pathway. TUBB6 silencing suppressed the WNT signaling pathway, with WNT3A and FZD8 identified as downstream targets. Conclusions: Collectively, our research shed light on the pivotal function of TUBB6 in maintaining ocular homeostasis and uncovered the YBX1-TUBB6-WNT3A/FZD8 pathway's involvement in sprouting angiogenesis. Targeting TUBB6 and developing its specific inhibitor could pioneer new approaches for treating ocular microvascular diseases.},
}
@article {pmid40083383,
year = {2025},
author = {Wu, P and Zhao, L and Du, Y and Lu, J and He, Y and Shu, Q and Peng, H and Wang, X},
title = {Melatonin protects retinal pigment epithelium cells against ferroptosis in AMD via the PI3K/AKT/MDM2/P53 pathway.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1543575},
pmid = {40083383},
issn = {1663-9812},
abstract = {INTRODUCTION: Oxidative stress-prompted degeneration of the retinal pigment epithelium (RPE) notably contributes to the onset of age-related macular degeneration (AMD). However, the pathways leading to RPE deterioration and possible preventative strategies are not yet completely comprehended.<br><br>METHODS: Ferroptosis was assayed through the evaluation of lipid peroxidation (C11-BODIPY and MDA), reactive oxygen species (ROS), transmission electron microscopy (TEM), iron content measurement, q-PCR, western blotting, and immunofluorescence. To assess the structure and retinal function of RPE in mice, ERG (electroretinography), OCT (optical coherence tomography), and H&amp;E (hematoxylin and eosin) staining were employed. Network pharmacology methods were utilized to elucidate the potential mechanisms underlying melatonin's protective effects against ferroptosis in RPE cells in AMD. Genetic engineering techniques were applied to investigate the regulatory relationships among phosphatidylinositol 3-kinase (PI3K), protein kinase-B (AKT), murine double minute-2 (MDM2), protein 53 (P53), and solute carrier family 7 member 11 (SLC7A11). In vitro knockdown experiments of MDM2 were conducted to explore its regulatory role in ferroptosis within RPE cells.<br><br>RESULTS: A&#x3b2;1-40 can trigger ferroptosis in RPE cells. Melatonin can inhibit the oxidative stress and ferroptosis induced by A&#x3b2;1-40 in RPE cells. Melatonin exhibits a protective effect on A&#x3b2;1-40-induced AMD, significantly improving the structure of the mouse retina and RPE layer, and facilitating the restoration of visual function. Network pharmacology methods revealed that the potential targets of melatonin in AMD are closely related to ferroptosis, and indicated that the predominant pathways are significantly associated with the PI3K/AKT/MDM2/P53 signaling pathway. Knocking down the specific expression of MDM2 can significantly weaken the inhibitory effect of melatonin on oxidative stress and ferroptosis.<br><br>DISCUSSION: Melatonin can suppress cell death by ferroptosis in RPE via the PI3K/AKT/MDM2/P53 pathway, thereby preventing and decelerating the progression of AMD.},
}
@article {pmid40082667,
year = {2025},
author = {Luo, X and Ruan, Z and Liu, L},
title = {Causal effect of the 25-Hydroxyvitamin D concentration on ocular diseases: A Mendelian randomization study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8701},
pmid = {40082667},
issn = {2045-2322},
mesh = {Humans ; *Vitamin D/analogs &amp; derivatives/blood ; Mendelian Randomization Analysis ; *Eye Diseases/genetics/blood/epidemiology/etiology ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; },
abstract = {Observational studies report controversial associations between vitamin D levels and ocular diseases. We investigated the potential causal effect of 25-hydroxyvitamin D [25(OH)D] on ocular diseases using two-sample Mendelian randomization (MR). We examined associations between 25(OH)D and various ocular diseases including age-related macular degeneration, cataracts, diabetic retinopathy, myopia, glaucoma, conjunctivitis, keratitis and optic neuritis. Data were from genome-wide association studies of 25(OH)D and ocular diseases. We performed MR analyses using inverse-variance weighted methods with sensitivity analyses. We found no significant causal relationships between 25(OH)D and ocular diseases (all P > 0.05). Tests for heterogeneity (P > 0.05) and pleiotropy (P > 0.05) supported the MR validity. Our MR analysis does not provide evidence supporting a causal relationship between 25(OH)D and ocular disease risk in Europeans. This suggests that previous epidemiological associations may stem from shared biological factors or confounders rather than direct causality. However, further research is needed to fully elucidate the complex relationships between vitamin D and ocular health.},
}
@article {pmid40081374,
year = {2025},
author = {Kaminska, K and Cancellieri, F and Quinodoz, M and Moye, AR and Bauwens, M and Lin, S and Janeschitz-Kriegl, L and Hayman, T and Barberán-Martínez, P and Schlaeger, R and Van den Broeck, F and Ávila Fernández, A and Fernández-Caballero, L and Perea-Romero, I and García-García, G and Salom, D and Mazzola, P and Zuleger, T and Poths, K and Haack, TB and Jacob, J and Vermeer, S and Terbeek, F and Feltgen, N and Moulin, AP and Koutroumanou, L and Papadakis, G and Browning, AC and Madhusudhan, S and Gränse, L and Banin, E and Sousa, AB and Coutinho Santos, L and Kuehlewein, L and De Angeli, P and Leroy, BP and Mahroo, OA and Sedgwick, F and Eden, J and Pfau, M and Andréasson, S and Scholl, HPN and Ayuso, C and Millán, JM and Sharon, D and Tsilimbaris, MK and Vaclavik, V and Tran, HV and Ben-Yosef, T and De Baere, E and Webster, AR and Arno, G and Sergouniotis, PI and Kohl, S and Santos, C and Rivolta, C},
title = {Bi-allelic variants in three genes encoding distinct subunits of the vesicular AP-5 complex cause hereditary macular dystrophy.},
journal = {American journal of human genetics},
volume = {112},
number = {4},
pages = {808-828},
pmid = {40081374},
issn = {1537-6605},
mesh = {Humans ; Male ; Female ; *Macular Degeneration/genetics/pathology ; Pedigree ; *Alleles ; Retinal Pigment Epithelium/pathology/metabolism ; Middle Aged ; Adult ; *Adaptor Proteins, Vesicular Transport/genetics ; Vesicular Transport Proteins/genetics ; },
abstract = {Inherited retinal diseases (IRDs) are a genetically heterogeneous group of Mendelian disorders that often lead to progressive vision loss and involve approximately 300 distinct genes. Although variants in these loci account for the majority of molecular diagnoses, other genes associated with IRD await molecular identification. In this study, we uncover bi-allelic assortments of 23 different (22 loss-of-function) variants in AP5Z1, AP5M1, and AP5B1 as independent causes of recessive IRD in members of 19 families from nine countries. Affected individuals, regardless of their genotypes, exhibit a specific form of macular degeneration, sometimes presenting in association with extraocular features. All three genes encode different subunits of the vesicular fifth adaptor protein (AP-5) complex, a component of the intracellular trafficking system involved in maintaining cellular homeostasis and ensuring the proper functioning of lysosomal pathways. The retinal pigment epithelium (RPE), a cellular monolayer located posteriorly to the neural retina, is characterized by intense lysosomal and phagocytic activity. Immunostaining of RPE cells revealed a punctate pattern of AP5Z1, AP5M1, and AP5B1 staining and co-localization with markers of late endosomes and the Golgi, suggesting a role of AP-5 in the normal physiology of this tissue. Overall, the identification of independently acting variants in three distinct proteins within the same macromolecular complex reveals AP-5 as having an important function in the preservation and maintenance of normal macular functions.},
}
@article {pmid40080669,
year = {2024},
author = {Bottazzi, L and Servillo, A and Zucchiatti, I and Sacconi, R and Querques, L and Bandello, F and Querques, G},
title = {FLUCTUATING EXUDATION IN NON-NEOVASCULAR GEOGRAPHIC ATROPHY.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001629},
pmid = {40080669},
issn = {1937-1578},
abstract = {PURPOSE: To report a case series of exudation in non-neovascular geographic atrophy (GA), which fluctuated and spontaneously almost resolved during the follow-up.<br><br>METHODS: A retrospective study was designed to include consecutive cases with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) associated with intraretinal fluid (IRF) but without macular neovascularization (MNV). Three eyes of 2 patients (one male, one female) were enrolled. Spectral domain optical coherence tomography (SD-OCT) and angiographies (OCT angiography and/or dye angiographies) were performed to confirm diagnosis of IRF and the absence of MNV.<br><br>RESULTS: At baseline best-corrected visual acuity (BCVA) was between 20/50 and 20/36. SD-OCT displayed IRF in the inner and outer retinal layers with an increased central macular thickness. OCT-A and dye angiographies did not show any abnormal neovascular network. Of note, fluorescein angiography showed a leakage in correspondence of the intraretinal cysts, differently from the degenerative pseudocysts. After one month of follow-up, BCVA remained stable, while the IRF spontaneously almost resolved in all cases.<br><br>DISCUSSION: To our knowledge, this is the first report of a fluctuating exudation in non-neovascular GA. Future studies are required to better define this potential novel clinical phenotype.},
}
@article {pmid40080238,
year = {2025},
author = {Hu, A and Teneralli, RE and Rodriguez, R and Abdul Sultan, A and Garey, C and Ackert, J and Ong, R},
title = {Falls and Fractures in Patients with Geographic Atrophy: A US Claims Data Analysis.},
journal = {Advances in therapy},
volume = {42},
number = {5},
pages = {2234-2247},
pmid = {40080238},
issn = {1865-8652},
mesh = {Humans ; *Accidental Falls/statistics &amp; numerical data ; Female ; Aged ; Male ; Retrospective Studies ; *Fractures, Bone/epidemiology/etiology ; United States/epidemiology ; Aged, 80 and over ; *Geographic Atrophy/complications/epidemiology ; Insurance Claim Review ; Risk Factors ; Databases, Factual ; },
abstract = {INTRODUCTION: The increased risk of falls in elderly people represents a substantial public health burden that may be compounded by impaired visual acuity. The present study aimed to assess the independent risk of incident falls and fractures in patients with geographic atrophy (GA).<br><br>METHODS: This retrospective, noninterventional, cohort study analyzed three US claims datasets (Optum's de-identified Clinformatics[&#xae;] Data Mart Database [Clinformatics[&#xae;]], Merative&#x2122; MarketScan[&#xae;] Commercial and Medicare Databases [MarketScan], and IQVIA US PharMetrics[&#xae;] [PharMetrics]). Patients were defined as having at least one International Classification of Diseases, Tenth Revision code (H35.31x3, H35.31x4) for GA. A propensity score-matched control cohort, matched on age, sex, index year, and disease history, was also included. Relative risks (RRs) for incident falls, fractures, and health care resource utilization (HCRU) were calculated between GA and control cohorts.<br><br>RESULTS: The Clinformatics[&#xae;], MarketScan, and PharMetrics datasets included 44,591, 9470, and 27,428 patients with GA, respectively. Across the three databases, mean (SD) age ranged from 75.9 (8.3) to 80.5 (7.2) years, and 61% to 64% were female. The largest subgroup was patients with bilateral GA without subfoveal involvement (35-37%), followed by unilateral GA without subfoveal involvement (23-24%). Risks of falls (RR 1.16-1.36) and fractures (RR 1.17-1.29) in the 4&#xa0;years following the index date were higher in patients with GA compared with controls. Patients with bilateral GA and subfoveal involvement had the most pronounced increase in risk of falls (RR 1.42-1.49) and fractures (RR 1.33-1.45). Compared to controls, patients with GA also had an increased risk for hospitalization (RR 1.18-1.27), emergency department visits (RR 1.18-1.21), nursing home or assisted living admissions (RR 1.06-1.28), and outpatient visits (RR 1.05-1.08).<br><br>CONCLUSION: GA represents an independent risk factor for falls, fractures, and higher HCRU. These data reveal the substantial public health burden of GA associated with the management of falls and fractures.},
}
@article {pmid40079929,
year = {2025},
author = {Yousif, JE and Johnson, MW},
title = {Presumed Pentosan Polysulfate Maculopathy With Limited Drug Exposure.},
journal = {JAMA ophthalmology},
volume = {143},
number = {4},
pages = {362-363},
doi = {10.1001/jamaophthalmol.2025.0214},
pmid = {40079929},
issn = {2168-6173},
}
@article {pmid40079155,
year = {2025},
author = {Sun, Y and Zhang, W and Hu, B and Sun, B and Zhang, T and Yu, S and Yuan, G and Dai, R and Fan, K and Wang, L and Cheng, P and An, G and An, L and Wang, F and Chen, W and Zhang, J and Zhou, X and Wang, F and Ye, J and Huang, X and Peng, X and Li, J and Wu, M and Wan, G and Zhong, J and Ha, S and Ke, X and Liang, J and Qi, H and Yin, H and Qian, T and Qu, J and Shi, X and Hou, J and Miao, H and Yao, Y and Jin, E and Deng, X and Zhang, J and Shi, X and Liu, J and Ma, J and Liu, J and Tao, Y and Liu, B and Li, X and Zhao, M},
title = {Treat-And-Extend Versus Pro Re Nata Regimen of Intravitreal Conbercept Injection for Neovascular Age-Related Macular Degeneration: Results from COCOA, a Prospective, Open-Label, Multicenter, Randomized Phase IV Clinical Trial.},
journal = {Seminars in ophthalmology},
volume = {40},
number = {5},
pages = {393-399},
doi = {10.1080/08820538.2025.2467853},
pmid = {40079155},
issn = {1744-5205},
mesh = {Humans ; Intravitreal Injections ; Female ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity ; Aged ; Prospective Studies ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Middle Aged ; Tomography, Optical Coherence ; Aged, 80 and over ; Follow-Up Studies ; Dose-Response Relationship, Drug ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; },
abstract = {PURPOSE: To evaluate and contrast the effectiveness and safety of two conbercept treatment protocols-a three-dose treat-and-extend (3+T&amp;E) regimen and a three-dose pro re nata (3+PRN) regimen-in Chinese patients diagnosed with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Eligible patients, who had not undergone anti-VEGF intraocular injections within 3 months prior to enrollment, were randomly assigned to either the 3+T&amp;E or 3+PRN regimen. The 3+T&amp;E group received at least three monthly injections, with subsequent visit intervals extended based on disease activity assessment. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 48, using a predefined noninferiority threshold.<br><br>RESULTS: Among 501 participants (249 in 3+T&amp;E, 252 in 3+PRN), approximately half had prior anti-VEGF treatment. At 48&#x2009;weeks, both regimens showed significant BCVA improvements (+9.9 for 3+PRN, +8.6 for 3+T&amp;E; p&#x2009;=&#x2009;.208), with comparable rates of&#x2009;&#x2265;15-letter gains (32.12% for 3+PRN, 30.77% for 3+T&amp;E; p&#x2009;=&#x2009;.827). The 3+PRN group received fewer injections (mean 6.4 vs. 6.9 in 3+T&amp;E; p&#x2009;=&#x2009;.028) but had shorter intervals between injections (6.93&#x2009;weeks vs. 7.46&#x2009;weeks in 3+T&amp;E; p&#x2009;=&#x2009;.010). Drug-related adverse events occurred in 5% of patients, with ocular events evenly distributed and minimal cardiovascular events reported.<br><br>CONCLUSION: Both 3+T&amp;E and 3+PRN conbercept regimens effectively improved visual and anatomical outcomes in Chinese nAMD patients. The 3+T&amp;E regimen was noninferior to 3+PRN in improving BCVA from baseline to week 48. The 3+T&amp;E regimen enabled longer injection intervals while 3+PRN regimen with less injections is more cost-effective while maintaining a comparable safety profile. Treatment plan tailored to an individual patient's situation appears necessary.},
}
@article {pmid40078048,
year = {2025},
author = {Yanagi, Y and Tsujimura, J and Ohno, S and Higashi, K and Sakashita, N and Shoji, A and Igarashi, A},
title = {Cost-effectiveness analysis of bispecific antibody faricimab for treatment of neovascular age-related macular degeneration and diabetic macular edema in Japan.},
journal = {Journal of medical economics},
volume = {28},
number = {1},
pages = {448-459},
doi = {10.1080/13696998.2025.2478755},
pmid = {40078048},
issn = {1941-837X},
mesh = {Humans ; Cost-Benefit Analysis ; Markov Chains ; Japan ; Quality-Adjusted Life Years ; *Macular Edema/drug therapy ; Ranibizumab/economics/therapeutic use ; Recombinant Fusion Proteins/economics/therapeutic use ; *Angiogenesis Inhibitors/economics/therapeutic use ; *Diabetic Retinopathy/drug therapy ; *Antibodies, Bispecific/economics/therapeutic use ; *Macular Degeneration/drug therapy ; Aged ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Antibodies, Monoclonal, Humanized/economics/therapeutic use ; Male ; Female ; Cost-Effectiveness Analysis ; },
abstract = {OBJECTIVE: To assess the cost-effectiveness of faricimab vs. other anti-vascular endothelial growth factor (anti-VEGF) drugs for treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in Japan, while considering societal burden associated with treatment.<br><br>METHODS: A Markov model for cost-effectiveness analysis of anti-VEGF treatment in patients with nAMD and DME was applied based on cost and utility value data from Japan. Faricimab administered through a treat-and-extend (T&amp;E) regimen was compared with ranibizumab administered pro re nata (PRN) and T&amp;E, aflibercept T&amp;E, brolucizumab T&amp;E, and best supportive care (BSC). Further to treatment costs (public payer perspective), the societal burden (societal perspective), including costs of travel, informal care, and productivity, was assessed.<br><br>RESULTS: In treatment of nAMD, lifetime quality-adjusted life years (QALYs) gained were highest with faricimab (faricimab T&amp;E: 6.92, ranibizumab PRN: 6.88, ranibizumab T&amp;E: 6.91, aflibercept T&amp;E: 6.89, brolucizumab T&amp;E: 6.89, BSC: 5.99). From the public payer perspective, the lifetime total cost for faricimab T&amp;E was lower than those for ranibizumab (PRN, T&amp;E) and brolucizumab (T&amp;E), comparable to aflibercept T&amp;E, and higher than BSC (incremental costs: 158,385 and 6,475,511 JPY, respectively). As a result, faricimab was cost-effective or dominant in the treatment of nAMD, excluding BSC. From the societal perspective, faricimab was dominant against all comparators in nAMD. In treatment of DME, QALYs gained were highest with faricimab (faricimab T&amp;E: 8.51, ranibizumab PRN: 8.17, aflibercept PRN: 8.36, ranibizumab T&amp;E: 8.13, BSC: 5.16). From both the public payer and societal perspectives, faricimab was dominant against all comparators in DME.<br><br>CONCLUSIONS: When societal burdens were considered, faricimab was dominant in both nAMD and DME against all comparators, suggesting that the extended dosing interval associated with faricimab treatment may alleviate societal burdens and consequently improve patient outcomes.},
}
@article {pmid40077641,
year = {2025},
author = {Agrón, E and Vance, E and Domalpally, A and Chew, EY and Keenan, TDL},
title = {Relationships Between Diet and Geographic Atrophy Progression in the Age-Related Eye Diseases Studies 1 and 2.},
journal = {Nutrients},
volume = {17},
number = {5},
pages = {},
pmid = {40077641},
issn = {2072-6643},
support = {National Eye Institute Intramural Research Program//National Eye Institute Intramural Research Program/ ; },
mesh = {Humans ; Disease Progression ; Female ; Male ; Aged ; *Diet, Mediterranean ; *Geographic Atrophy/epidemiology/physiopathology ; Middle Aged ; Micronutrients/administration &amp; dosage ; Aged, 80 and over ; *Diet ; Fruit ; Vegetables ; },
abstract = {Background/Objectives: The objective of this study was to analyze the relationships between diet and geographic atrophy (GA) progression, both area-based and proximity-based, for dietary pattern, components, and micronutrients. Methods: In the Age-Related Eye Diseases Study (AREDS) and AREDS2, an Alternative Mediterranean Diet Index (aMedi), its nine components, and individual micronutrient intakes were calculated. Mixed-model regression was performed for square root GA area, GA foveal proximity, and acuity. Results: The study populations comprised 657 (AREDS) and 1179 eyes (AREDS2). For area-based progression, a higher aMedi was associated with slower progression in AREDS2 and (in analyses excluding MUFA:SFA) AREDS. A higher intake was associated with slower progression for seven components (including vegetables and fruit at Bonferroni) and four components (including fruit and less red meat at Bonferroni), and seven and 15 nutrients, in AREDS1/2, respectively. For proximity-based progression, a higher aMedi was associated with slower progression in AREDS. A higher intake was associated with slower progression for three components (including vegetables at Bonferroni) and two components, and 10 and 8 nutrients, in AREDS1/2, respectively. With increasing oral supplementation, associations between proximity-based progression and aMedi/components/nutrients were weaker. In AREDS2 eyes with non-central GA, higher aMedi was associated with a slower acuity decline. Conclusions: A Mediterranean-type diet is associated with slower GA area-based progression and slower progression to the fovea, accompanied by a slower decline in acuity. The most important components and micronutrients for incidence, area-based progression, and foveal progression overlap only partially. For the latter two, they include vegetables, fruit, and less red meat. These findings suggest the benefits of targeted nutritional and supplementation strategies.},
}
@article {pmid40076952,
year = {2025},
author = {Chen, C and Wang, H and Yang, J and Zhao, B and Lei, Y and Li, H and Yang, K and Liu, B and Diao, Y},
title = {Sodium Iodate-Induced Ferroptosis in Photoreceptor-Derived 661W Cells Through the Depletion of GSH.},
journal = {International journal of molecular sciences},
volume = {26},
number = {5},
pages = {},
pmid = {40076952},
issn = {1422-0067},
support = {82301227//National Natural Science Foundation of China/ ; 2023YNCX001//Open Fund of Yunnan Key Laboratory of Tea Science/ ; ZQN-1213//Fundamental Research Funds for the Central Universities of Huaqiao University/ ; 2023J05049//Natural Science Foundation of Fujian Province/ ; 3502Z202371017//Youth Innovation Foundation of Xiamen/ ; 22BS115//Scientific Research Funds of Huaqiao University/ ; },
mesh = {*Ferroptosis/drug effects ; *Iodates/pharmacology ; *Glutathione/metabolism ; Animals ; Reactive Oxygen Species/metabolism ; Lipid Peroxidation/drug effects ; Cell Line ; *Photoreceptor Cells, Vertebrate/metabolism/drug effects ; Mice ; Oxidative Stress/drug effects ; Macular Degeneration/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/drug effects ; *Photoreceptor Cells/metabolism/drug effects ; Iron/metabolism ; },
abstract = {Oxidative stress-induced photoreceptor cell death is closely associated with the etiology of age-related macular degeneration (AMD), and sodium iodate (SI) has been widely used as an oxidant stimulus in AMD models to induce retinal pigment epithelium (RPE) and photoreceptor cell death. However, the mechanism underlying SI-induced photoreceptor cell death remains controversial and unclear. In this study, we elucidate that ferroptosis is a critical form of cell death induced by SI in photoreceptor-derived 661W cells. SI disrupts system Xc[-], leading to glutathione (GSH) depletion and triggering lipid peroxidation, thereby promoting ferroptosis in photoreceptor-derived 661W cells. Additionally, SI enhances intracellular Fe[2+] levels, which further facilitates reactive oxygen species (ROS) accumulation, making the 661W cells more susceptible to ferroptosis. Exogenous GSH, as well as specific inhibitors of ferroptosis such as Fer-1 and antioxidants like NAC, significantly attenuate SI-induced ferroptosis in photoreceptor-derived 661W cells. These findings provide new insights into the mechanisms of ferroptosis as a key pathway in SI-induced photoreceptor-derived 661W cell death.},
}
@article {pmid40076793,
year = {2025},
author = {Pieńczykowska, K and Bryl, A and Mrugacz, M},
title = {Link Between Metabolic Syndrome, Inflammation, and Eye Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {5},
pages = {},
pmid = {40076793},
issn = {1422-0067},
mesh = {Humans ; *Metabolic Syndrome/complications/metabolism/pathology ; *Eye Diseases/metabolism/etiology/pathology ; *Inflammation/metabolism/complications/pathology ; Animals ; Oxidative Stress ; },
abstract = {Metabolic syndrome (MetS)-a cluster of conditions including obesity, hypertension, dyslipidemia, and insulin resistance-is increasingly recognized as a key risk factor for the development of various eye diseases. The metabolic dysfunctions associated with this syndrome contribute to vascular and neurodegenerative damage within the eye, influencing disease onset and progression. Understanding these links highlights the importance of early diagnosis and management of metabolic syndrome to prevent vision loss and improve ocular health outcomes. This review explores the intricate interplay between metabolic syndrome, chronic low-grade inflammation, and eye diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and dry eye syndrome. It highlights how inflammatory mediators, oxidative damage, and metabolic dysregulation converge to compromise ocular structures, including the retina, optic nerve, and ocular surface. We discuss the molecular and cellular mechanisms underpinning these associations and examine evidence from clinical and experimental studies. Given the rising global prevalence of metabolic syndrome, addressing this connection is crucial for improving overall patient outcomes and quality of life. Future research should focus on delineating the precise mechanisms linking these diseases as well as exploring targeted interventions that address both metabolic and ocular health.},
}
@article {pmid40075380,
year = {2025},
author = {Schikora, J and Dort, A and Wolf, HN and Józsi, M and Pouw, RB and Bertelmann, T and Bahlmann, D and van Oterendorp, C and Feltgen, N and Hoerauf, H and Pauly, D and Klemming, J},
title = {Decreased complement 4 and interleukin-10 as biomarkers in aqueous humour for non-exudative age-related macular degeneration: a case control study.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {317},
pmid = {40075380},
issn = {1479-5876},
support = {899163//H2020 Future and Emerging Technologies/ ; },
mesh = {Humans ; *Aqueous Humor/metabolism ; *Biomarkers/metabolism ; *Macular Degeneration/metabolism ; Female ; Male ; *Interleukin-10/metabolism ; Case-Control Studies ; Aged ; Middle Aged ; Pilot Projects ; },
abstract = {BACKGROUND: The development of age-related macular degeneration (AMD) is influenced by risk factors that contribute to inflammatory processes, cellular stress responses, and a dysregulation of the complement system. Given the incomplete understanding of the pathogenesis of AMD and the necessity for novel therapeutics, biomarker studies investigating aqueous humour from the anterior chamber of the eye serve as a valuable tool. This pilot study aimed to assess inflammatory mediators and complement components in aqueous humour of non-exudative AMD patients in comparison with a control group.<br><br>METHODS: The aqueous humour of 12 non-exudative AMD patients and 21 control subjects was collected during cataract surgery. Levels of 78 inflammatory proteins and complement components were measured using multiplex immunoassays. The influence of sex or smoking on the AMD status was assessed using Pearson's chi-square test. Biomarker levels between AMD patients vs. controls, smokers vs. non-smokers, and females vs. males were compared. Parametric datasets were analysed using independent-means t-test, while non-parametric data analysis was conducted utilising Wilcoxon's rank-sum test. Spearman's correlation investigated associations between drusen volume and biomarker levels, as well as biomarker levels and subject age.<br><br>RESULTS: All examined 78 immunological factors were detectable in aqueous humour. The proteins were categorised into high, medium, and low level groups. Aqueous humour contained high levels of complement proteins, including iC3b, FH/FHL-1, C4B, and FI. Non-exudative AMD patients exhibited decreased levels of C4 (P&#x2009;=&#x2009;0.020), IL-10 (P&#x2009;=&#x2009;0.033), and FI (P&#x2009;=&#x2009;0.082). A positive correlation was observed between drusen volume and CCL4 levels (rS&#x2009;=&#x2009;0.78, P&#x2009;=&#x2009;0.013). Furthermore, smokers demonstrated significantly increased levels of pro-inflammatory proteins (CCL7, IL-7; P&#x2009;=&#x2009;0.027, P&#x2009;=&#x2009;0.030). MMP-1 was positively correlated with age (rS&#x2009;=&#x2009;0.44, P&#x2009;=&#x2009;0.010), while sex differences were observed in FB (P&#x2009;=&#x2009;0.027) and C4B (P&#x2009;=&#x2009;0.036) levels.<br><br>CONCLUSIONS: This pilot study presents an initial overview of inflammation-associated biomarkers in the aqueous humour, highlighting potential roles for C4 and IL-10 in the development of non-exudative AMD. A larger, more-focused follow-up study is in progress to further investigate biomarkers localised to the eye and refine our understanding of AMD.},
}
@article {pmid40075283,
year = {2025},
author = {Pauleikhoff, L and Ziegler, M and Bachmeier, I and Yu, S and Armendariz, BG and Pauleikhoff, D},
title = {Retinal sensitivity above macular neovascularization under anti-VEGF therapy in exudative neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {123},
pmid = {40075283},
issn = {1471-2415},
mesh = {Humans ; Aged ; Female ; Male ; *Angiogenesis Inhibitors/therapeutic use ; Tomography, Optical Coherence ; Pilot Projects ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Visual Acuity/physiology ; Intravitreal Injections ; Visual Field Tests ; *Retina/physiopathology/pathology ; Ranibizumab/therapeutic use ; Visual Fields/physiology ; Fluorescein Angiography ; *Choroidal Neovascularization/physiopathology/drug therapy ; Retinal Pigment Epithelium/pathology ; },
abstract = {PURPOSE: Growth of macular neovascularization (MNV) associated with development of complete retinal pigment epithelial and outer retina atrophy (cRORA) been observed in eyes neovascular age-related macular degeneration (nAMD) under effective anti-vascular endothelial growth factor (VEGF) therapy. We aimed to evaluate the influence of the presence of MNV on the sensitivity of the overlaying retina both in patients with or without cRORA and to generate hypotheses about their association.<br><br>METHODS: Pilot study on nAMD patients undergoing long-term anti-VEGF therapy that had also undergone microperimetry testing. Area of MNV and, if present, associated cRORA were identified on optical coherence tomography (OCT) volume scans and transposed onto en-face near-infrared images. Mesopic microperimetry performed at the same visit was then superimposed. Retinal sensitivity above the MNV and the surrounding retina were compared, excluding areas of cRORA.<br><br>RESULTS: Twenty-six eyes (19 f, 7&#xa0;m; age 79.3&#x2009;&#xb1;&#x2009;5.7 y; fu 4.0&#x2009;&#xb1;&#x2009;1.8 y; 7.4&#x2009;&#xb1;&#x2009;2.5 inj./y) were classified into a no cRORA (n&#x2009;=&#x2009;11) and a cRORA group (n&#x2009;=&#x2009;15). In the no cRORA group, mean retinal sensitivity above the MNV did not differ from the surrounding retina (20.9&#x2009;&#xb1;&#x2009;2.8 vs. 22.0&#x2009;&#xb1;&#x2009;2.4, p&#x2009;=&#x2009;0.33), while in the cRORA group, a lower sensitivity above the MNV in comparison to the surrounding retina was observed (16.2&#x2009;&#xb1;&#x2009;3.4 vs. 19.9&#x2009;&#xb1;&#x2009;2.0, p&#x2009;=&#x2009;0.001).<br><br>CONCLUSION: In the absence of cRORA, retinal sensitivity above the MNV did not differ significantly from that of the surrounding retina. These results could indicate a possible nutritional function of the MNV to the overlying retina in cases where no cRORA is present.},
}
@article {pmid40075135,
year = {2025},
author = {Bai, S and Zhang, L and Yan, W and Wang, H},
title = {A cross-sectional observational study of the association between biochemistry profiles and the risk of age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8588},
pmid = {40075135},
issn = {2045-2322},
support = {2024ms18//General Cultivation Project of Municipal Health Commission in Xi'an, China/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology/blood/metabolism ; Cross-Sectional Studies ; Male ; Female ; Aged ; Middle Aged ; Risk Factors ; Nutrition Surveys ; Bilirubin/blood ; Uric Acid/blood ; Biomarkers/blood ; Aged, 80 and over ; },
abstract = {This study aimed to explore the relationship between biochemical profiles and the risk of age-related macular degeneration (AMD) through a cross-sectional observational analysis. We examined data of U. S. population from the 2005-2008 National Health and Nutrition Examination Survey (NHANES) database. Student's t-test, multivariable logistic regression, Pearson's correlation, restricted cubic spline (RCS) model, and linear regression were applied to analyze the underlying relationship between biochemical profiles and the AMD risk, through comparing data between the non-AMD and AMD subgroups. Multivariable logistic regression, adjusted for age and demographic factors, showed no significant associations between the AMD risk and the levets of specific biochemical parameters (P > 0.05). Pearson's correlation revealed a positive linear relationship between age and total bilirubin, uric acid in the non-AMD subgroup (P < 0.05), but no such liner association was found in the AMD subgroup (P > 0.05). The RCS model confirmed no non-linear relationships presented between these variables in the AMD subgroup. In addition, without age adjustment, significant associations were found between total bilirubin, uric acid, and the AMD presence (P < 0.05). Biochemical profiles, after adjusting for age, did not significantly influence the AMD risk. However, total bilirubin and uric acid might potentially be related to the AMD presence. Our findings suggest a need for further research to clarify the role of these biomarkers in AMD development.},
}
@article {pmid40075010,
year = {2025},
author = {Sacconi, R and Marra, S and Spada, E and Beretta, F and Menna, M and Menecozzi, S and Bandello, F and Querques, G},
title = {Geographic Atrophy Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Progression of the Disease at 2-Year Follow-Up.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {5},
pages = {911-922},
pmid = {40075010},
issn = {2193-8245},
abstract = {INTRODUCTION: The purpose of the study is to characterize the rate of progression of geographic atrophy (GA) areas in patients with age-related macular degeneration (AMD) with subclinical angioid streaks (AS), compared to patients with AMD without subclinical AS.<br><br>METHODS: This is a retrospective, longitudinal, case-control study. Among a cohort of patients&#xa0;with AMD, we selected patients with GA with subclinical AS and followed them for a 2-year follow-up. An age- and sex-matched control group with GA secondary to AMD without subclinical AS was selected. Demographics and differences in the GA progression between the two groups were analyzed.<br><br>RESULTS: Among 60 eyes of 60 patients affected by GA secondary to AMD, 20 eyes of 20 patients (mean age 82&#x2009;&#xb1;&#x2009;5 years old) were included in the subclinical AS group, whereas 40 eyes of 40 patients (mean age 79&#x2009;&#xb1;&#x2009;6&#xa0;years old, p&#x2009;=&#x2009;0.077)&#xa0;were in the control group. All 20 eyes of subclinical AS group showed reticular pseudodrusen at the baseline compared to 73% of patients without AS (p&#x2009;=&#x2009;0.002). In the subclinical AS group, 90% of eyes showed peripapillary atrophy in comparison to 63% in the control group (p&#x2009;=&#x2009;0.026). Subclinical AS eyes showed a significantly lower subfoveal choroidal thickness in comparison to the control group (124&#x2009;&#xb1;&#x2009;60&#xa0;&#x3bc;m vs. 161&#x2009;&#xb1;&#x2009;84&#xa0;&#x3bc;m, respectively, p&#x2009;=&#x2009;0.043). At 2-year follow-up, the rate of progression was higher in the patients with subclinical AS; the yearly growth rate was 0.41&#x2009;&#xb1;&#x2009;0.17&#xa0;mm/year after the square root transformation in the subclinical AS group, in comparison to 0.32&#x2009;&#xb1;&#x2009;0.14&#xa0;mm/year in the control group (p&#x2009;=&#x2009;0.017).<br><br>CONCLUSIONS: Patients with subclinical AS showed a more aggressive phenotype of GA in comparison to AMD patients without subclinical AS, characterized by a higher rate of progression of GA areas during a 2-year follow-up.},
}
@article {pmid40074767,
year = {2025},
author = {Markakis, D and Britten-Jones, AC and Guymer, RH and Edwards, TL and Hall, AJ and Kerr, NM and Ng, W and Skalicky, S and Ayton, LN and Mack, HG},
title = {Retrospective audit reviewing accuracy of clinical diagnosis of geographic atrophy in a single centre private tertiary retinal practice in Australia.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8528},
pmid = {40074767},
issn = {2045-2322},
support = {Postdoctoral Scholarship//University of Melbourne/ ; Driving Research Momentum Fellowship//University of Melbourne/ ; Operational Infrastructure Support Program//State Government of Victoria/ ; 1195713//National Health and Medical Research Council/ ; },
mesh = {Humans ; Retrospective Studies ; *Geographic Atrophy/diagnosis ; Australia/epidemiology ; Aged ; Male ; Female ; Middle Aged ; Diagnostic Errors ; Macular Degeneration/diagnosis ; Aged, 80 and over ; Clinical Audit ; },
abstract = {Accurate diagnosis of both age-related macular degeneration (AMD) and inherited retinal diseases (IRD) with macular atrophy is important because treatments for both conditions are emerging. Phenotypical similarities between macular atrophy associated with AMD (geographic atrophy, GA) and IRD-associated atrophy exist, which can make accurate diagnosis challenging in clinical practice. Misdiagnosis may lead to inappropriate treatment strategies and missed opportunities for disease-specific interventions. A retrospective clinical review of medical records of people diagnosed with AMD between 1995 and 2023 from a large multidisciplinary private ophthalmic practice in Australia was undertaken to identify cases of patients diagnosed with geographic atrophy without drusen, which was then further assessed for potentially missed IRD with macular atrophy. Flagged cases were presented to experts in AMD and IRD to establish a most-likely diagnosis. Cases without consensus between graders were grouped into most-likely diagnosis by a third senior retinal clinician. Of the 1136 cases reviewed, the possible rate of misdiagnosis observed was 1.9%, with 1.0% representing potentially missed IRDs, most commonly pattern dystrophy (0.5%). A multi-modal approach, including clinical features and patient history, is important to limit the possibility of misdiagnosis of GA, and identify a subset of patients who might benefit from genetic testing prior to considering possible treatments.},
}
@article {pmid40072892,
year = {2025},
author = {Li, T and Wang, Y and Chen, X and Cui, H and Zhang, L and Liu, J and Wang, J and Wang, X and Zhao, Y and Chen, Q and Wang, J},
title = {Direct Cytosolic Delivery of siRNA Conjugates: A Paradigm in Antiangiogenic Therapy for Choroidal Neovascularization.},
journal = {ACS nano},
volume = {19},
number = {11},
pages = {11249-11262},
doi = {10.1021/acsnano.4c18924},
pmid = {40072892},
issn = {1936-086X},
mesh = {*RNA, Small Interfering/chemistry/administration &amp; dosage/genetics/metabolism ; *Choroidal Neovascularization/drug therapy/therapy/genetics/pathology ; Humans ; Animals ; *Cytosol/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/chemistry/pharmacology ; Mice ; },
abstract = {Small interfering RNA (siRNA) has garnered tremendous interest as a potential therapeutic tool because of its intriguing gene-silencing ability. Toward the success in the manufacture of siRNA therapeutics for the potential treatment of choroidal neovascularization (CNV), siRNA conjugated with dual functional units of membrane-penetrating heptafluoropropyl and age-related macular degeneration-targeting cyclic Arg-Gly-Asp (RGD) peptide was attempted for transcellular transportation into the cell interiors. Of note, cyclic RGD allowed selective affinities toward the angiogenic endothelial cells in the pathological CNV. Noteworthy is the functional heptafluoropropyl group, due to its tempting lipophobic and hydrophobic properties, stimulating energy-independent transcellular trafficking behaviors to the cytoplasm directly from the extracellular compartments, namely, the nonendocytotic pathway. The behaviors manage to avoid the well-acknowledged drawback of endolysosomal entrapment, which is deemed to be the critical threat to the biovulnerable genomic therapeutics, thereby contributing to potent gene knockdown at the affected cells. Aiming for treatment of CNV, the siRNA duo was schemed with appropriate chemistry-based modifications for the targeted knockdown of both angiogenic VEGF-A and VEGF-R2. Subsequent investigations verified the potent reduction of vascular leakage, and our proposed siRNA duo accomplished a significant reduction of 67.3% in the mean area of the CNV lesion. Bioinformatic analysis has unveiled a multitude of therapeutic benefits conferred by anti-VEGF therapy, extending beyond the mere inhibition of angiogenesis, including the regulated leukocyte transendothelial migration, retinol metabolism, and estrogen signaling pathways. Hence, our proposed chemistry represents an interesting siRNA conjugate strategy accomplishing direct intracellular transportation of macromolecular biological payloads to the cytosol. Hence, this proposed fluorination strategy should be highlighted to encourage the development of appropriate prodrug chemistry in pursuit of transcellular trafficking of membrane-impermissible and biovulnerable biotherapeutics.},
}
@article {pmid40072815,
year = {2025},
author = {Honjo, J and Mukai, R and Itagaki, K and Tanaka, K and Norikawa, K and Kato, Y and Kasai, A and Sugano, Y and Sekiryu, T},
title = {Comparison of intraocular pressure changes in Japanese patients with neovascular age-related macular degeneration treated with aflibercept or faricimab.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {2},
pages = {230-235},
pmid = {40072815},
issn = {1613-2246},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; *Intraocular Pressure/drug effects/physiology ; Aged ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Japan/epidemiology ; Aged, 80 and over ; Follow-Up Studies ; Visual Acuity ; Tomography, Optical Coherence ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Tonometry, Ocular ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; East Asian People ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To assess the short-term changes in intraocular pressure (IOP) following intravitreal injections of aflibercept or faricimab in Japanese patients with neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: This retrospective observational study included 161 eyes from 160 Japanese patients diagnosed with nAMD. Of these, 127 eyes (127 patients) were treated with 2&#xa0;mg/0.05 mL aflibercept, and 34 eyes (33 patients) received 6&#xa0;mg/0.05 mL faricimab. Each group underwent three consecutive monthly injections. The IOP in each treated eye was measured using non-contact tonometry at each visit over a 3-month period following the initial injection.<br><br>RESULTS: The mean baseline IOP in the aflibercept group was 14.4&#x2009;&#xb1;&#x2009;2.8 mmHg, decreasing to 13.2&#x2009;&#xb1;&#x2009;3.0 mmHg after 3 months (P&#x2009;<&#x2009;0.001), whereas the mean baseline IOP in the faricimab group was 13.8&#x2009;&#xb1;&#x2009;2.1 mmHg, with a change to 13.5&#x2009;&#xb1;&#x2009;1.5 mmHg after 3 months (P&#x2009;=&#x2009;0.1873).<br><br>CONCLUSION: The loading phase treatment with aflibercept resulted in a decrease in IOP. Faricimab showed a similar trend, there was no significant difference between the two treatments.},
}
@article {pmid40072810,
year = {2025},
author = {Fiore, T and De Santi, N and Bianchi, E and Cerquaglia, A and Lupidi, M and Tosi, G and Cagini, C},
title = {Safety of intravitreal injections with the mobile laminar airflow device Operio after more than 10.000 injections.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {86},
pmid = {40072810},
issn = {1573-2630},
mesh = {Humans ; Retrospective Studies ; *Intravitreal Injections/adverse effects/instrumentation ; Aged ; Male ; Female ; Endophthalmitis/epidemiology/etiology ; Middle Aged ; Aged, 80 and over ; *Angiogenesis Inhibitors/administration &amp; dosage ; Glucocorticoids/administration &amp; dosage ; Visual Acuity ; *Retinal Diseases/drug therapy ; },
abstract = {PURPOSE: To evaluate the occurrence of complications following intravitreal injections (IVIs) performed in an outpatient clean room (OCR) equipped with the mobile laminar airflow device (LAF) Operio.<br><br>METHODS: This retrospective study analyzed the data of 10,016 IVIs performed in an OCR from April 2023 to November 2024. All information of each patient was registered, such as diagnosis, drug injected and any occurring complication or adverse events such as endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment (RRD), vitreous hemorrhages and elevated intraocular pressure.<br><br>RESULTS: From April 2023 to November 2024, 10,016 IVIs were performed in 1700 eyes of 1460 patients with the average age of 76.10&#x2009;&#xb1;&#x2009;12.37&#xa0;years. The most representative diagnosis were Age-related Macular Degeneration (AMD) (47.60%), Retinal Vein Occlusion (RVO) (18.90%) and Diabetic Macular Edema (DME) (8.42%). Ten (4.24%) cases of ocular hypertensions were reported after dexamethasone implant whereas no cases of endophthalmitis or RRD were registered.<br><br>CONCLUSIONS: The OCR equipped with Operio was easy to set up, safe regarding all IVI-related complications, first and foremost endophthalmitis, helpful in improving the management of IVIS, and allowed us to decongest the operating room for more complex surgeries.},
}
@article {pmid40071859,
year = {2025},
author = {Borrás-Blasco, J and Abad, J and Cornejo-Uixeda, S and Perez Gil, L and Zarco Bosquet, J},
title = {Economic impact of a faricimab vial-sharing protocol in age-related macular degeneration and diabetic macular oedema patients.},
journal = {Acta ophthalmologica},
volume = {103},
number = {5},
pages = {e341-e342},
doi = {10.1111/aos.17483},
pmid = {40071859},
issn = {1755-3768},
}
@article {pmid40070018,
year = {2025},
author = {Klingeborn, M and Arora, V and Chung, C and Donchenko, P and Wright, RN and Reese, ED and Gunn, TM},
title = {Desmosome and Hemidesmosome Release via Exosomes from Retinal Pigmented Epithelium - A Precursor to Epithelial-Mesenchymal Transition in Early AMD?.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-10},
pmid = {40070018},
issn = {1460-2202},
support = {P20 GM152335/GM/NIGMS NIH HHS/United States ; R21 EY033057/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: This minireview discusses desmosome and hemidesmosome disassembly and/or internalization and subsequent release via exosomes in retinal pigmented epithelium (RPE) under oxidative stress conditions, and whether it may be a precursor to epithelial-mesenchymal transition in early Age-related Macular Degeneration (AMD).<br><br>METHODS: Literature review and discussion of novel findings relevant to the focus of the review.<br><br>RESULTS: The RPE forms the outer blood-retinal barrier, and like other epithelia it has several different types of cell-cell junctions, such as desmosomes. The RPE provides key metabolic and nutrient support to photoreceptors and the function of normal vision. The RPE is a principal location of disease-associated changes in AMD, due to its essential role in visual homeostasis. Exosomes are lipid bilayer membrane vesicles of nanometer sizes that are released via a dedicated machinery by all cells and carry out a multitude of functions related to cellular signaling and waste management. In the RPE they are released from both the apical and basal sides, and the cargo composition reflects this polarization. We have recently showed that exosomes released from the basolateral side of RPE cells under chronic oxidative stress conditions, contain desmosome and hemidesmosome proteins. Here we discuss the composition of desmosomes and hemidesmosomes in the RPE, the role of exosomes and ubiquitination pathways in their disassembly, and whether this dismantling is a precursor to epithelial-mesenchymal transition. Further considerations include how the exosome-mediated shedding of desmosome and hemidesmosome components is related to lysosomal and/or proteasomal overload, and how these pathways can be modulated to intervene in early stages of AMD.<br><br>CONCLUSIONS: This review provides an overview of the current knowledge about desmosome and hemidesmosome disassembly in RPE, its intersection with the exosome pathway, and potential role in epithelial-mesenchymal transition. We discuss several potential targets for therapeutic intervention in pre-symptomatic or early-stage AMD in these pathways.},
}
@article {pmid40067096,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Xu, J and Wei, WB and Wang, YX},
title = {Associations of fundus tessellation, myopic diffuse chorioretinal atrophy and choroidal thickness with visual acuity in myopia.},
journal = {Acta ophthalmologica},
volume = {103},
number = {8},
pages = {1010-1019},
doi = {10.1111/aos.17480},
pmid = {40067096},
issn = {1755-3768},
support = {2019-4//Beijing Municipal Health Commission/ ; 82271086//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Visual Acuity/physiology ; Male ; *Choroid/pathology ; Female ; Middle Aged ; *Tomography, Optical Coherence/methods ; *Myopia, Degenerative/physiopathology/diagnosis/complications ; Fundus Oculi ; Aged ; Cross-Sectional Studies ; *Myopia/physiopathology/diagnosis/complications ; *Fluorescein Angiography/methods ; Retrospective Studies ; Follow-Up Studies ; Corneal Dystrophies, Hereditary ; },
abstract = {PURPOSE: To explore associations between stages of myopic macular degeneration (MMD) and visual acuity and influencing parameters.<br><br>METHODS: Participants of the population-based study Beijing Eye Study (n&#x2009;=&#x2009;3468 participants) underwent a detailed ocular and systemic examination.<br><br>RESULTS: Assessable images were available for 3040 (87.7%) individuals (age: 64.0&#x2009;&#xb1;&#x2009;9.7&#x2009;years). In multivariable analysis, worse best-corrected visual acuity (BCVA) (i.e. higher logMAR values) was associated with higher MMD stage (beta: 0.11; B: 0.06; 95% CI: 0.04, 0.08; p&#x2009;<&#x2009;0.001) and thinner subfoveal choroidal thickness (beta: -0.06; p&#x2009;=&#x2009;0.002), with adjustments for age, sex, educational level, cognitive function, degree of any cataract and prevalence of glaucoma, diabetic retinopathy and age-related macular degeneration. If only eyes with MMD grade 1 or no MMD were included, worse BCVA was associated (multivariable analysis) with higher prevalence of MMD stage 1 (beta: 0.11; B: 0.07; 95% CI: 0.05, 0.09; p&#x2009;<&#x2009;0.001) and thinner medium-sized choroidal vessel layer thickness. Correspondingly, BCVA was worse in eyes with MMD stage 1 than in eyes without MMD (0.13&#x2009;&#xb1;&#x2009;0.27 logMAR vs. 0.04&#x2009;&#xb1;&#x2009;0.14; p&#x2009;<&#x2009;0.001). Including only eyes without vision-influencing disorders (except myopia), BCVA was also worse in eyes with MMD stage 1 than in eyes without MMD (0.06&#x2009;&#xb1;&#x2009;0.13 logMAR vs. -0.01&#x2009;&#xb1;&#x2009;0.08 logMAR; p&#x2009;<&#x2009;0.001). In these eyes without vision-influencing ocular disorders, worse BCVA was associated with thinner total subfoveal choroidal thickness (beta: -0.15; R: 0.000; 95% CI: 0.000, 0.000; p&#x2009;<&#x2009;0.001) and longer axial length (beta: 0.14; R: 0.01; 95% CI: 0.01, 0.02; p&#x2009;<&#x2009;0.001), or alternatively with higher MMD staging (beta: 0.24; R: 0.09; 95% CI: 0.01, 0.11; p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: MMD stage 1 (fundus tessellation) is associated with decreased BCVA and may be considered pathological. Independently of longer axial length, thinner choroidal thickness is a factor associated with lower BCVA in myopic eyes, including eyes with MMD stage 1.},
}
@article {pmid40065869,
year = {2025},
author = {Kamath, S and Charlotte, A and Nandan, N},
title = {Silicone Oil Droplets in the Vitreous After an Anti-vascular Endothelial Growth Factor (VEGF) Injection: A Complication of Syringe Lubrication.},
journal = {Cureus},
volume = {17},
number = {2},
pages = {e78715},
pmid = {40065869},
issn = {2168-8184},
abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) injections are a cornerstone treatment for various retinal conditions, including diabetic macular edema and age-related macular degeneration. While generally safe, these injections can introduce unintended substances, such as silicone oil droplets, into the vitreous cavity due to the silicone-based lubricant used in syringe manufacturing. Although frequently asymptomatic, silicone oil droplets can occasionally cause significant visual disturbances and discomfort. We report a rare case of symptoms caused by silicone oil droplets following a single intravitreal bevacizumab injection. A 54-year-old diabetic male patient presented with pain and iridescent floaters in his right eye, which began immediately after receiving an intravitreal bevacizumab injection and persisted for four weeks. The patient, with a 20-year history of diabetes and prior scatter laser photocoagulation, exhibited a visual acuity of 20/80 in the right eye or oculus dexter (OD) and 20/40 in the left eye or oculus sinister (OS), with an elevated intraocular pressure (IOP) of 24 mmHg in the right eye. Dilated fundoscopy revealed multiple silicone oil droplets floating in the vitreous cavity, alongside severe non-proliferative diabetic retinopathy and macular edema. The patient was started on anti-glaucoma medications, brimonidine, and timolol, which effectively reduced his IOP to 18 mmHg within a week. Despite IOP control, the patient remained distressed by persistent floaters, which gradually became less symptomatic with time. This case is unique because the symptoms due to the silicone oil droplets occurred after a single injection, unlike most reports of asymptomatic presentations or those arising after multiple injections. The disproportionate amount of silicone oil observed raises concerns about syringe design and transport conditions. While silicone oil is inert, its presence can cause the patient anxiety and visual disturbances.},
}
@article {pmid40065587,
year = {2025},
author = {Bunch, KT and May, HT and Knowlton, KU and Bair, TL and Muhlestein, JB and Anderson, JL and Ranjan, R and Steinberg, BA and Bunch, TJ},
title = {Atrial Fibrillation as a Predictor of Age-Related Macular Degeneration.},
journal = {Journal of cardiovascular electrophysiology},
volume = {36},
number = {5},
pages = {990-995},
doi = {10.1111/jce.16627},
pmid = {40065587},
issn = {1540-8167},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; *Atrial Fibrillation/epidemiology/diagnosis/physiopathology/drug therapy ; Female ; Aged ; Male ; Middle Aged ; *Macular Degeneration/epidemiology/diagnosis ; Risk Factors ; Incidence ; Time Factors ; Risk Assessment ; Prospective Studies ; Age Factors ; Aged, 80 and over ; Databases, Factual ; },
abstract = {BACKGROUND: Aging of the population has resulted in more patients living with atrial fibrillation (AF) and age-related macular degeneration (AMD). AF is associated with macro- and micro-thromboembolism, microvascular dysfunction, and system inflammation. Organ systems sensitive to the long-term systemic and vascular disease associations of AF will likely develop dysfunction over time. There is also an increase in age-related macular degeneration (AMD), which shares many pathophysiologic risk factors of AF. We hypothesized that AF will increase the risk of AMD.<br><br>METHODS: A total of 38&#x2009;746 consecutive patients from the large ongoing prospective angiography INSPIRE Study database without a history of AMD were evaluated for the development of AMD. Long-term incidence of AMD was assessed at 1 and 5 years and at last follow-up to determine its association with AF.<br><br>RESULTS: Over a mean follow-up of 2159.4&#x2009;&#xb1;&#x2009;1851.7 days, 11&#x2009;787 (30.4%) had or developed AF. Patients with AF were older (67.7&#x2009;&#xb1;&#x2009;12.2 vs. 57.5&#x2009;&#xb1;&#x2009;15.5 years, p&#x2009;<&#x2009;0.0001), and had higher rates of hypertension (50.0% vs. 44.0%, p&#x2009;<&#x2009;0.0001), renal failure (1.7% vs. 1.1%, p&#x2009;<&#x2009;0.0001), stroke (4.6% vs. 3.1%, p&#x2009;<&#x2009;0.0001), and heart failure (27.3% vs. 11.5%, p&#x2009;<&#x2009;0.0001). AF patients were more likely to be treated with a statin, ACE/ARB, diuretic, and warfarin. The overall incidence of AMD over the follow-up period was higher in patients with AF (2.1% vs. 1.2%, p&#x2009;<&#x2009;0.0001). Compared with no AF, the risk of AMD in patients with AF was increased at 1 year (hazard ratio [HR]&#x2009;=&#x2009;1.92 [1.26-2.93], p&#x2009;=&#x2009;0.003), 5 years (HR&#x2009;=&#x2009;1.83 [1.46-2.29], p&#x2009;<&#x2009;0.0001), and long-term (1.80 [1.52-2.12], p&#x2009;<&#x2009;0.0001). The association of AF with AMD was attenuated after adjustment by baseline characteristics, comorbidities, and medications. All AMD risks were mitigated in multivariable modeling that included baseline characteristics (i.e., CHA2DS2-Vasc) and drug therapies for AF.<br><br>CONCLUSION: Patients with AF are at elevated risk of developing AMD that increases over time when compared to patients without AF. In this cohort of patients, the risk of AMD is due to risk factors that drive the presence of AF itself and its progression. Comprehensive treatment of AF that focuses on its underlying risk factors, including dynamic reassessment of risk factors during follow-up, may impact risk of AMD in patients with AF.},
}
@article {pmid40065260,
year = {2025},
author = {Bantounou, MA and Elsheikh, M and Ijasan, A and Santiago, C},
title = {Real-world experience of intravitreal faricimab injection in previously treated neovascular age-related macular degeneration eyes: a case series.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {117},
pmid = {40065260},
issn = {1471-2415},
mesh = {Humans ; Male ; Intravitreal Injections ; Female ; Retrospective Studies ; Aged, 80 and over ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Treatment Outcome ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: Faricimab is a novel anti-vascular endothelial growth factor agent, used to treat patients with neovascular age-related macular degeneration (nAMD). This study assessed efficacy and safety of faricimab in previously treated eyes.<br><br>METHODS: This retrospective study included previously treated nAMD patients who had received at least three faricimab injections. Baseline data were collected from February 2023 to September 2023, and follow-up data were collected until April 2024. The patients were divided into two cohorts: (1) the "Loaded" cohort, which received four weekly injections prior to treatment extension, and (2) the "Interval-Matched" cohort, which continued on the same treatment interval as their previous regimen. Efficacy was evaluated based on the primary outcome measures: central subfield thickness (CST), the presence of macular fluid, and visual outcomes. Safety was assessed through the secondary outcome measure of adverse event reporting.<br><br>RESULT: Two hundred thirty-seven participants (297 eyes) were included with a mean age of 80.7&#x2009;&#xb1;&#x2009;7&#xa0;years, 44% were males. 2,237 faricimab injections were administered (7.5&#x2009;&#xb1;&#x2009;1.9 per eye). In the loaded cohort, CST decreased from 315.1&#x2009;&#xb1;&#x2009;86.0&#xa0;&#xb5;m to 288.0&#x2009;&#xb1;&#x2009;63.6&#xa0;&#xb5;m (p&#x2009;<&#x2009;0.001). The percentage of dry macula increased from 11.0% to 42.5% (p&#x2009;<&#x2009;0.001). Vision changed from 67.9&#x2009;&#xb1;&#x2009;12.3 to 69.3&#x2009;&#xb1;&#x2009;13.4 letters (p&#x2009;=&#x2009;0.002), and the injection interval extended from 5.3&#x2009;&#xb1;&#x2009;1.3 to 6.4&#x2009;&#xb1;&#x2009;2.1&#xa0;weeks (p&#x2009;<&#x2009;0.001). For the interval-matched cohort, CST decreased from 302.8&#x2009;&#xb1;&#x2009;57.4&#xa0;&#xb5;m to 291.2&#x2009;&#xb1;&#x2009;62.6&#xa0;&#xb5;m (p&#x2009;=&#x2009;0.001). The percentage of dry macula increased from 22.5% to 47.7% (p&#x2009;<&#x2009;0.001). Vision changed from 65.9&#x2009;&#xb1;&#x2009;13.8 to 65.0&#x2009;&#xb1;&#x2009;17.1 letters (p&#x2009;=&#x2009;0.613), and the injection interval extended from 6.6&#x2009;&#xb1;&#x2009;2.8 to 7.9&#x2009;&#xb1;&#x2009;3.2&#xa0;weeks (p&#x2009;<&#x2009;0.001). 68 (28.7%) adverse events were reported, of which 9 (3.8%) were serious.<br><br>CONCLUSION: Faricimab showed beneficial anatomical response with stable vision, and less injections. The loaded cohort exhibited superior outcomes but needed more injections.},
}
@article {pmid40065020,
year = {2025},
author = {Vofo, BN and Shwartz, Y and Cnaany, Y and Jaskoll, S and Kramer, A and Elbaz-Hayoun, S and Rinsky, B and Grunin, M and Tiosano, L and Chowers, I},
title = {Long-term macular atrophy growth in neovascular age-related macular degeneration: influential factors and role of genetic variants.},
journal = {Eye (London, England)},
volume = {39},
number = {9},
pages = {1717-1723},
pmid = {40065020},
issn = {1476-5454},
support = {3485/19//Israel Science Foundation (ISF)/ ; },
mesh = {Humans ; Aged ; Male ; Female ; Retrospective Studies ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy/genetics/diagnosis ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Atrophy ; Visual Acuity/physiology ; *Macula Lutea/pathology ; *Proteins/genetics ; Risk Factors ; Follow-Up Studies ; Tomography, Optical Coherence ; Middle Aged ; Fluorescein Angiography ; Genetic Variation ; },
abstract = {OBJECTIVES: This retrospective cohort study aimed to assess the long-term growth and associated risk factors of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) compounds.<br><br>METHODS: Two hundred and six patients initiating anti-VEGF therapy were followed for 8 years using a treat-and-extend protocol. The study analysed correlations between MA growth (by square root transformation measured in infrared images) and clinical parameters, and genetic variants for AMD in the complement and lipid pathways and the ARMS2 gene.<br><br>RESULTS: Seventy-six patients (n&#x2009;=&#x2009;92 eyes) were included, with a mean age of 73.9&#x2009;&#xb1;&#x2009;7.9 years. Eyes received an average of 7.1&#x2009;&#xb1;&#x2009;3.2 anti-VEGF injections per year. The prevalence of MA increased from 28.3% at baseline to 78.3% at 8 years, exhibiting an average annual growth rate of 0.25&#x2009;&#xb1;&#x2009;0.22&#x2009;mm. Correlations were found between MA growth and size, and number of atrophic foci at baseline, and the common ARMS2 variant. Eyes with subretinal fluid (SRF) at baseline showed less foveal atrophy at 8 years compared to those with IRF or both IRF and SRF. No correlation was observed between MA growth and genetic variants in the complement and lipid pathways.<br><br>CONCLUSION: Most eyes with nAMD under 8 years of anti-VEGF therapy developed MA, with significant growth. Correlations with baseline MA characteristics and the ARMS2 variant were identified. Further investigation is needed to understand the potential role of complement as a therapeutic target for preventing macular atrophy in nAMD-affected eyes.},
}
@article {pmid40062093,
year = {2025},
author = {Kapetanaki, MV and Maliagkani, E and Tyrlis, K and Georgalas, I},
title = {Artificial Intelligence in Myopic Maculopathy: A Comprehensive Review of Identification, Classification, and Monitoring Using Diverse Imaging Modalities.},
journal = {Cureus},
volume = {17},
number = {2},
pages = {e78685},
pmid = {40062093},
issn = {2168-8184},
abstract = {This review investigates the usefulness and effectiveness of artificial intelligence (AI) tools in the detection of myopic maculopathy lesions using traditional imaging techniques like fundus photography and optical coherence tomography (OCT). The role of machine learning (ML) and deep learning (DL) algorithms in the diagnosis, classification, and follow-up of highly myopic cases is discussed. A comprehensive analysis of articles published between 2018 and 2024 from PubMed, Science Direct-Elsevier, and Google Scholar identified 13 studies directly relevant to the topic. The majority of the studies were conducted in China and focused on patients with myopic macular degeneration and high myopia. The most popular AI algorithms included ResNet-18, ResNet-50, ResNet-101, DeepLabv3+ and DarkNet-19, Efficient Net (B0/B7), VOLO-D2, Efficient Former, ALFA-Mix+, and XGBoost. Reported statistical metrics ranged from 80% to 97.3% for accuracy, 80% to 99.8% for the area under the curve (AUC), 83.0% to 97.0% for sensitivity, 63.0% to 97.21% for specificity, and 0.8358 to 0.9880 for the kappa value. The findings reveal that AI models can play a supportive role in disease diagnosis, achieving performance metrics comparable to those of general ophthalmologists. Furthermore, the utilization of larger datasets of OCT and fundus images improves generalizability and diagnostic accuracy. The integration of multimodal imaging techniques, such as OCT, color fundus photographs, and ultra-wide field photographs, enhances diagnostic clinical value and enables more comprehensive disease monitoring.},
}
@article {pmid40059223,
year = {2025},
author = {Gandhewar, R and Guimaraes, T and Sen, S and Pontikos, N and Moghul, I and Empeslidis, T and Michaelides, M and Balaskas, K},
title = {Imaging biomarkers and artificial intelligence for diagnosis, prediction, and therapy of macular fibrosis in age-related macular degeneration: Narrative review and future directions.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {7},
pages = {1789-1800},
pmid = {40059223},
issn = {1435-702X},
mesh = {Humans ; *Artificial Intelligence ; *Tomography, Optical Coherence/methods ; Fibrosis/diagnosis ; *Biomarkers/metabolism ; *Macula Lutea/pathology/diagnostic imaging ; *Fluorescein Angiography/methods ; *Wet Macular Degeneration/complications/diagnosis ; Prognosis ; },
abstract = {Macular fibrosis is an end-stage complication of neovascular Age-related Macular Degeneration (nAMD) with a complex and multifactorial pathophysiology that can lead to significant visual impairment. Despite the success of anti-vascular endothelium growth factors (anti-VEGF) over the last decade that revolutionised the management and visual prognosis of nAMD, macular fibrosis develops in a significant proportion of patients and, along with macular atrophy (MA), is a main driver of long-term vision deterioration. There remains an unmet need to better understand macular fibrosis and develop anti-fibrotic therapies. The use of imaging biomarkers in combination with novel Artificial Intelligence (AI) algorithms holds significant potential for improving the accuracy of diagnosis, disease monitoring, and therapeutic discovery for macular fibrosis. In this review, we aim to provide a comprehensive overview of the current state of knowledge regarding the various imaging modalities and biomarkers for macular fibrosis alongside outlining potential avenues for AI applications. We discuss manifestations of macular fibrosis and its precursors with diagnostic and prognostic significance on various imaging modalities, including Optical Coherence Tomography (OCT), Colour Fundus Photography (CFP), Fluorescein Angiography (FA), OCT-Angiography (OCTA) and collate data from prospective and retrospective research on known biomarkers. The predominant role of OCT for biomarker identification is highlighted. The review coincides with a resurgence of intense research interest in academia and industry for therapeutic discovery and clinical testing of anti-fibrotic molecules.},
}
@article {pmid40059179,
year = {2025},
author = {Jang, W and Kim, Y and Kim, H},
title = {Association between the dietary omega-6 to omega-3 fatty acid ratio and age-related macular degeneration in Korean adults.},
journal = {Nutrition journal},
volume = {24},
number = {1},
pages = {29},
pmid = {40059179},
issn = {1475-2891},
mesh = {Humans ; *Fatty Acids, Omega-3/administration &amp; dosage ; Female ; Male ; *Macular Degeneration/epidemiology ; Republic of Korea/epidemiology ; *Fatty Acids, Omega-6/administration &amp; dosage ; Cross-Sectional Studies ; Middle Aged ; Aged ; Nutrition Surveys ; *Diet/statistics &amp; numerical data/methods ; Prevalence ; },
abstract = {BACKGROUND: Long-chain polyunsaturated fatty acids of the omega-6 and omega-3 families affect processes implicated in vascular and neural retinal disease pathogenesis. This study aimed to investigate the association between the dietary omega-6 to omega-3 fatty acid ratio and age-related macular degeneration (AMD).<br><br>METHODS: We conducted a cross-sectional analysis using a nationwide representative sample of older adults (&#x2265;&#x2009;50 years), including 1,944 men and 2,592 women, from the Korea National Health and Nutrition Examination Survey (2017-2018). Omega-6 and omega-3 fatty acid intakes were collected through a 24-hour recall method and used to calculate the omega-6 to omega-3 fatty acid ratio. Associations between the ratio and AMD were determined using odds ratios (ORs) from multivariate logistic regressions.<br><br>RESULTS: The prevalence of AMD was 19.8% and 17.7% in Korean men and women, respectively. In women, the multivariable-adjusted OR for incurring AMD was significantly higher in the 2nd (OR&#x2009;=&#x2009;1.36; 95% CI&#x2009;=&#x2009;1.02-1.81) and 3rd (OR&#x2009;=&#x2009;1.36; 95% CI&#x2009;=&#x2009;1.02-1.83) tertiles of the dietary omega-6 to omega-3 fatty acid ratio than in the 1st tertile (OR&#x2009;=&#x2009;1, the reference OR) (P&#x2009;=&#x2009;0.036 for this trend). However, this association was not observed in men.<br><br>CONCLUSIONS: These results suggest that high omega-6 to omega-3 fatty acid ratios may be associated with an increased prevalence of AMD among Korean women.},
}
@article {pmid40058064,
year = {2025},
author = {Capuano, V and Semoun, O and Combes, A and Mehanna, CJ and Oubraham, H and Souied, EH},
title = {[Diagnostic approach and treatment paradigm in atrophic age related macular degeneration: Recommendations of the France Macula Federation].},
journal = {Journal francais d'ophtalmologie},
volume = {48},
number = {4},
pages = {104473},
doi = {10.1016/j.jfo.2025.104473},
pmid = {40058064},
issn = {1773-0597},
mesh = {Humans ; *Macular Degeneration/therapy/diagnosis ; France ; Tomography, Optical Coherence ; Fluorescein Angiography ; Visual Acuity ; Geographic Atrophy/therapy/diagnosis ; },
abstract = {Atrophic age-related macular degeneration (AMD) represents a detrimental progression of age-related maculopathy, characterized by advanced retinal lesions associated with drusen and pseudodrusen as well as alterations in the outer retinal layers and RPE. It is characterized by a thinning of the neuroretinal tissue linked to the disappearance of the outer layers of the retina and the RPE. Our goal is to offer to ophthalmologists recommendations in the diagnosis and management of atrophic AMD with a standardized approach, in order to facilitate and optimize the management of this disease. The diagnosis of atrophic AMD is based on multimodal imaging; color fundus photography, autofluorescence images of the fundus (AFF) and structural optical coherence tomography (OCT) are the first-line examinations to assess lesion size and foveolar sparing. OCT-angiography (OCT-A) is useful in diagnosing associated choroidal neovascularization. At times, the differential diagnosis will require other complementary examinations, such as fluorescein and/or indocyanine green angiography. The assessment of visual function is essentially based on the measurement of visual acuity; other functional tests such as reading speed, measurement of visual acuity in low luminance (LLVA), contrast sensitivity or microperimetry are of definite interest, but are not yet used in routine clinical practice. The therapeutic solutions for this pathology are multidisciplinary; they combine regular clinical monitoring, medical treatment, psychological support, orthoptic rehabilitation and optical visual aids. Support groups are of significant benefit.},
}
@article {pmid40057009,
year = {2025},
author = {Wang, Z and Yu, Y and Ye, Y and Wang, L and Bao, Y and Wang, X and Zhou, X and Zhao, J},
title = {Associations Between Ambient Air Pollution and Five Common Vision-Threatening Ocular Diseases in Middle-Aged and Older Adults: A Large Prospective Cohort Study.},
journal = {American journal of ophthalmology},
volume = {274},
number = {},
pages = {276-285},
doi = {10.1016/j.ajo.2025.03.009},
pmid = {40057009},
issn = {1879-1891},
mesh = {Humans ; Prospective Studies ; Male ; Female ; Middle Aged ; *Air Pollution/adverse effects ; Incidence ; Aged ; Particulate Matter/adverse effects/analysis ; *Air Pollutants/adverse effects ; *Diabetic Retinopathy/epidemiology/etiology ; Risk Factors ; United Kingdom/epidemiology ; *Cataract/epidemiology/etiology ; *Macular Degeneration/epidemiology/etiology ; *Glaucoma/epidemiology/etiology ; *Retinal Detachment/epidemiology ; *Eye Diseases/epidemiology ; Follow-Up Studies ; Nitrogen Oxides ; },
abstract = {PURPOSE: Ambient air pollution may exacerbate ocular conditions; however, comprehensive research on the effects of various pollutants remains limited. This study aims to evaluate the association between multiple air pollutants and the incidence of five common vision-threatening ocular diseases: cataracts, glaucoma, macular degeneration, diabetic retinopathy, and retinal detachment.<br><br>DESIGN: Prospective cohort study.<br><br>METHODS: We included 114,930 participants with refractometry at baseline in this prospective cohort study based on data from the UK Biobank. Annual average concentrations of nitrogen oxides (NOx), nitrogen dioxide (NO2), and particulate matter (PM) with diameters <2.5 &#xb5;m (PM2.5) and <10 &#xb5;m (PM10) were assessed using land use regression models. Restricted cubic spline models and Cox proportional hazards regression were used to estimate the association between air pollution exposure and ocular disease incidence, with stratified analyses based on myopia status.<br><br>RESULTS: An interquartile range increase in PM10 and NOx was significantly associated with a higher risk of diabetic retinopathy among participants with myopia, with hazard ratios of 1.11 (95% confidence interval: 1.01-1.23) and 1.22 (95% confidence interval: 1.02-1.45), respectively. PM10 was linked to a 9% increase in retinal detachment incidence in the myopic population, and PM2.5 was linked to an 8% increase in glaucoma incidence in the nonmyopic population. High PM10 exposure was associated with a 61% higher risk of diabetic retinopathy in the myopic group. Further stratified analysis revealed that the impact of PM10 on diabetic retinopathy was more pronounced in individuals with low-to-moderate myopia than in those with high myopia. High PM10 exposure also correlated with a 67% higher risk of retinal detachment and a 44% higher risk of macular degeneration in the low-to-moderate myopic population.<br><br>CONCLUSIONS: Exposure to high levels of PM10 was associated with an increased risk of diabetic retinopathy and retinal detachment, highlighting the importance of addressing air pollutants as an intervention for vision-threatening ocular diseases.},
}
@article {pmid40056163,
year = {2025},
author = {Cinque, F and van den Tillaert, FM and Yzer, S and de Breuk, A and Heesterbeek, TJ and Hoyng, CB and Lechanteur, YT},
title = {Comparable choroidal thickness between treated eyes and untreated fellow-eyes in patients with unilateral neovascular AMD: a paired-eyes comparative study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {6},
pages = {1543-1551},
pmid = {40056163},
issn = {1435-702X},
support = {BHC-RD-SOP-038//Bayer/ ; Uitzicht-2021-32//Landelijke Stichting voor Blinden en Slechtzienden/ ; Uitzicht-2021-32//Algemene Nederlandse Vereniging ter voorkoming van Blindheid/ ; Uitzicht-2021-32//Stichting Beheer Het Schild via Steunfonds Uitzicht/ ; Uitzicht-2021-32//Oogfonds/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/pathology/diagnostic imaging ; Cross-Sectional Studies ; Female ; Male ; Angiogenesis Inhibitors/administration &amp; dosage ; Prospective Studies ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged ; Intravitreal Injections ; Fluorescein Angiography/methods ; *Ranibizumab/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; Follow-Up Studies ; Fundus Oculi ; Aged, 80 and over ; *Bevacizumab/administration &amp; dosage ; },
abstract = {AIMS: To investigate the potential effect of anti-VEGF treatment on choroidal thickness (CT) in unilateral neovascular age-related macular degeneration (AMD) patients.<br><br>METHOD: This is a cross-sectional study where patients were included as part of an ongoing prospective study which included patients with unilateral neovascular (n) AMD. The fellow-eye served as control. All patients had spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) done at every visit. CT was measured independently by two graders at five locations: subfoveal, 1500 micron temporal and nasal, 3000 micron temporal and nasal. The average of the measurements was used after statistical verification of their accuracy. CT differences were initially analysed via a paired T-test and later via multiple linear regression. Variables such as number of injections were studied and presence of geographic atrophy (GA) in fellow-eyes was evaluated via SD-OCT.<br><br>RESULTS: A total of 112 patients met the inclusion criteria (Female 67%). The median (IQR) years of treatment was 2.6 (4.1). The subfoveal choroidal thickness (SFCT) in the neovascular (NV) eye appeared thinner in the NNV eye initially (-11.0&#xa0;&#x3bc;m difference between NV and NNV SFCT (CI -23.4 to 1.3). However, after age-adjustment this trend disappeared (CI -29.8 to 4.6). In fact, apart from age (CI -6.2 to -0.1)), no other variable including number of anti-VEGF injections (CI -1.5 to 1.4) predicted SFCT. Presence of GA in fellow eyes did not influence the SFCT compared to non-GA fellow eyes, difference (CI -59.7 to 46.6).<br><br>CONCLUSIONS: This study shows no statistically significant CT difference in NV versus NNV eyes. There was no relationship between number of injections and CT.<br><br>KEY MESSAGES: What is known Intravitreal injection with anti-vascular endothelial growth factors (anti-VEGF) is the mainstay treatment for exudation secondary to neovascular AMD. One quarter of anti-VEGF treated neovascular AMD patients will develop signs of macular atrophy within 2 years, possibly related to anti-VEGF treatment. What this study adds A hypothesized mechanism for atrophy induction is the effect of anti-VEGF on choroidal thickness. In this cross-sectional study, we found a non-significant 11 micron difference between anti-VEGF treated eyes and non-treated eyes in long-term follow-up neovascular AMD patients. A relationship between choroidal thinning and the number of anti-VEGF injections was furthermore not shown. How this study might affect research, practice or policy There is no significant choroidal thickness difference between anti-VEGF treated and non-treated long-term follow-up neovascular AMD. We therefore suggest that atrophy induction through choroidal thinning secondary to anti-VEGF injections is of limited concern.},
}
@article {pmid40056085,
year = {2025},
author = {Zhang, M and Xu, J and Qu, W and Gao, J and Mo, Y},
title = {Advances in understanding the role and mechanism of the cGAS-STING signaling pathway in ocular diseases.},
journal = {Immunological medicine},
volume = {48},
number = {4},
pages = {266-280},
doi = {10.1080/25785826.2025.2475626},
pmid = {40056085},
issn = {2578-5826},
mesh = {Humans ; *Signal Transduction ; *Nucleotidyltransferases/metabolism ; *Membrane Proteins/metabolism ; Animals ; *Eye Diseases/metabolism/immunology/therapy ; },
abstract = {The cGAS-STING signaling pathway plays a critical role in the immune defense against DNA viruses and in autoimmunity, coordinating a cascade of events that enhance cytokine production, particularly type I interferons. This review summarizes recent advancements in understanding the pathway's impact on various ocular diseases, including age-related macular degeneration (AMD), diabetic retinopathy, and uveitis. Activation of this pathway by cytoplasmic DNA from either damaged retinal cells or external pathogens induces inflammatory responses that may accelerate disease progression. Moreover, the paper explores new therapeutic approaches that target this pathway, offering insights into how modulation of cGAS-STING signaling could reduce inflammation and improve clinical outcomes. The emerging research in this area suggests potential for innovative treatments in ocular inflammation and degenerative conditions.},
}
@article {pmid40055704,
year = {2025},
author = {Dai, Y and Cui, C and Jiao, D and Zhu, X},
title = {JAK/STAT signaling as a key regulator of ferroptosis: mechanisms and therapeutic potentials in cancer and diseases.},
journal = {Cancer cell international},
volume = {25},
number = {1},
pages = {83},
pmid = {40055704},
issn = {1475-2867},
abstract = {Ferroptosis is a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, playing a critical role in various diseases, including cancer, neurodegeneration, and tissue damage. This study reviews the intricate relationship between ferroptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, highlighting its regulatory functions across multiple biological processes. Dysregulation of the JAK/STAT pathway is implicated in promoting or inhibiting ferroptosis, depending on the context. JAK2 promotes ferroptosis by activating STAT proteins, modulating the expression of key regulators like SLC7A11 and GPX4, and influencing iron homeostasis through pathways such as ferritinophagy and hepcidin regulation. STAT1 activation primarily enhances ferroptosis through the suppression of cystine-glutamate antiporter (System Xc[-]), leading to glutathione depletion and lipid peroxidation, contributing to cell death in conditions like Sjogren's syndrome and age-related macular degeneration. In contrast, STAT3 plays a protective role by upregulating SLC7A11 and GPX4, which inhibits ferroptosis and promotes cell survival, particularly in cancers such as hepatocellular carcinoma, prostate cancer, and renal cell carcinoma. This study also discusses STAT6's involvement in ferroptosis suppression in diseases like asthma and lung injury by regulating antioxidant defenses. Furthermore, the review explores potential therapeutic strategies targeting the JAK/STAT pathway to manipulate ferroptosis for disease treatment. In cancer therapy, modulating this pathway can enhance the effectiveness of ferroptosis inducers, offering promising avenues to overcome drug resistance. Additionally, the interplay between ferroptosis and JAK/STAT signaling in immune responses, oxidative stress, and lipid metabolism underscores its significance in disease progression and therapeutic intervention. By exploring these mechanisms, this study provides insights into the development of novel treatments targeting ferroptosis through JAK/STAT modulation, with implications for cancer, inflammatory diseases, and neurodegenerative conditions.},
}
@article {pmid40055675,
year = {2025},
author = {Rajesh, A and Gong, J and Chan, KS and Viniak, R and Droho, S and Kachar, D and Strauss, JY and Wang, AL and Lavine, JA},
title = {The role of myeloid cell heterogeneity during spontaneous choroidal neovascularization in Vldlr knockout mice.},
journal = {Journal of neuroinflammation},
volume = {22},
number = {1},
pages = {70},
pmid = {40055675},
issn = {1742-2094},
support = {R01 EY034486/EY/NEI NIH HHS/United States ; Unrestricted Departmental Grant//Research to Prevent Blindness/ ; R01 EY036826/EY/NEI NIH HHS/United States ; New Investigator Award//BrightFocus Foundation/ ; K08 EY030923/EY/NEI NIH HHS/United States ; Medical Student Eye Research Fellowship//Research to Prevent Blindness/ ; },
mesh = {Animals ; *Receptors, LDL/genetics/deficiency ; Mice ; Mice, Knockout ; *Choroidal Neovascularization/pathology/genetics/metabolism ; *Myeloid Cells/metabolism/pathology/drug effects ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/deficiency ; Mice, Transgenic ; Receptors, CCR2/genetics/deficiency ; Macrophages ; Monocytes ; },
abstract = {BACKGROUND: Myeloid cells are heterogeneous cells that are critical for spontaneous choroidal neovascularization (CNV) in the Vldlr[-/-] mouse model. However, the specific myeloid cell subtype necessary for CNV remains unknown.<br><br>METHODS AND RESULTS: To investigate the role of monocytes, we bred Ccr2[-/-] and Nr4a1[-/-] mice into the Vldlr[-/-] background. We found that Ccr2 and Nr4a1 deficiency had no effect upon macrophage counts, CNV lesion number, or total CNV area. Next, we investigated the role of microglia by generating Vldlr[-/-]Tmem119[CreER/+]Rosa26[DTR/+] mice. Diphtheria toxin (DT) treatment reduced macrophage counts at CNV lesions and CNV lesion number, but did not affect total CNV lesion area. To target microglia via a second strategy, we generated Vldlr[-/-]Cx3cr1[CreER]Csf1r[iDTR] mice and treated them with a single low dose of tamoxifen to target microglia without affecting choroidal macrophages. DT treatment in Vldlr[-/-]Cx3cr1[CreER]Csf1r[iDTR] mice decreased macrophage counts at CNV lesions and CNV lesion number but again had no effect upon total CNV lesion area. To target choroidal macrophages and microglia, we treated Vldlr[-/-]Cx3cr1[CreER]Csf1r[iDTR] mice with 9 tamoxifen treatments. DT-treated mice showed dramatic reductions in macrophage counts, CNV number, and total lesion area.<br><br>CONCLUSIONS: These data suggest that monocytes and monocyte-derived macrophages are dispensable, microglia are likely initiators for CNV development, and choroidal macrophages are potential key contributors to CNV growth and/or maintenance in the Vldlr[-/-] model.},
}
@article {pmid40055462,
year = {2025},
author = {Straiko, MMW and Ellison, MS and Patzer, C and Westrick, K and Tran, KD},
title = {Provision of human ocular tissue for biomedical research: trends, limitations, and potential solutions from an eye bank.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {7958},
pmid = {40055462},
issn = {2045-2322},
mesh = {Humans ; *Eye Banks/trends ; *Biomedical Research/trends ; Tissue Donors ; Retrospective Studies ; *Tissue and Organ Procurement ; *Eye ; Macular Degeneration/pathology ; United States ; Female ; },
abstract = {Post-mortem donor eye tissues are essential for biomedical research. This study analyzes factors affecting donor eye availability for research through a retrospective review of recoveries at a U.S. eye bank between January 1, 2022, and December 31, 2023. Two time parameters were studied: death-to-recovery interval, defined as the time from death to tissue procurement, and post mortem interval (PMI), which accounts for the additional time required to transport tissue back to the laboratory for final preservation. The dataset was further stratified based on donor history for three ocular diseases frequently requested by researchers: age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. Among the eyes recovered specifically for research, only 32% of tissues met the < 12 h PMI requirement commonly requested by researchers. Further, only 27% of all research tissues meeting the < 12-hour PMI criterion arrived at the eye bank during current research staffing hours (8 AM-4 PM). The peak arrival time for research tissues was between 2 PM and 7 PM. The availability of tissues with PMI < 12 h further decreased for specific disease states. These findings highlight the logistical challenges of procuring donor eye tissues for research, particularly those with low PMIs. Adjustments by eye banks and researchers - such as extending staffing hours and relaxing strict PMI cutoffs - could significantly expand the donor pool for research. For example, if our eye bank extended research staffing by 3 h and researchers increased the allowable PMI to < 16 h, donor eye availability would increase by 223% over the current approach.},
}
@article {pmid40054647,
year = {2025},
author = {Aydin, R and Ozbek, M and Artunay, O},
title = {Multimodal imaging for evaluation and quantification of atrophy progression in extensive macular atrophy with pseudodrusen.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {53},
number = {},
pages = {104550},
doi = {10.1016/j.pdpdt.2025.104550},
pmid = {40054647},
issn = {1873-1597},
mesh = {Humans ; Aged ; Female ; Middle Aged ; *Tomography, Optical Coherence/methods ; *Multimodal Imaging/methods ; Male ; Disease Progression ; *Retinal Drusen/diagnostic imaging/pathology ; Atrophy ; *Macular Degeneration/diagnostic imaging/pathology ; Fluorescein Angiography/methods ; Geographic Atrophy/diagnostic imaging ; *Macula Lutea/pathology/diagnostic imaging ; },
abstract = {AIM: To present the atrophy progression rate with fundus autofluorescence (FAF) and optical coherence tomography (OCT) findings in patients with extensive macular atrophy with a pseudodrusen-like appearance.<br><br>METHODS: Eight patients who were followed up with the diagnosis of diffuse macular atrophy accompanied by pseudodrusen were included. Medical records, FAF, and OCT images at consecutive follow-ups were reviewed. Measurement of the atrophic area was performed on FAF images using the Heidelberg RegionFinder software at baseline and each annual visit until the last available follow-up.<br><br>RESULTS: The mean age was 56.75 &#xb1; 5.92 years (range, 45-65 years). Nyctalopia was observed in all patients. Macular atrophy of various sizes with a larger vertical diameter was present. Diffuse pseudodrusen-like deposits extending to the mid-peripheral retina were identified. The mean follow-up period was 38.33 &#xb1; 14.60 months (range, 26-60 months). The mean area of atrophy at baseline was 13.05 &#xb1; 7.93 mm[2] and reached 15.31 &#xb1; 7.93 mm[2] at the first-year follow-up (p < 0.001). At the end of the follow-up period, the mean area of atrophy was 17.32 &#xb1; 7.90 mm[2] (p = 0.001). The yearly rate of atrophy expansion was 2.13 mm[2]/year. The mean subfoveal choroidal thickness at baseline decreased markedly during the follow-up period (p = 0.000).<br><br>CONCLUSIONS: The progression rate of macular atrophy in these patients is faster than the geographic atrophy associated with age-related macular degeneration. In this era of therapeutic options, it has become more important to assess atrophy progression. Distinguishing different macular atrophy forms may be crucial for selecting suitable candidates for future interventional treatments.},
}
@article {pmid40054600,
year = {2025},
author = {Feo, A and Ramtohul, P and Govetto, A and Borrelli, E and Sacconi, R and Corradetti, G and Querques, G and Romano, MR and Rosenfeld, PJ and Spaide, RF and Freund, KB and Sadda, S and Sarraf, D},
title = {En face OCT: Breakthroughs in understanding the pathoanatomy of retinal disease and clinical applications.},
journal = {Progress in retinal and eye research},
volume = {106},
number = {},
pages = {101351},
doi = {10.1016/j.preteyeres.2025.101351},
pmid = {40054600},
issn = {1873-1635},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnosis/diagnostic imaging ; *Retina/pathology/diagnostic imaging ; },
abstract = {En face optical coherence tomography (OCT) is a practical and informative imaging modality to noninvasively visualize distinct retinal and choroidal layers by providing coronal images using boundary-specific segmentation. Ongoing research with this method is generating breakthroughs in the illustration of new perspectives of retinal disease. The clinical value of en face OCT as an advanced retinal imaging tool is growing steadily and it has unveiled many new insights into the pathoanatomy of retinal disorders. Moreover, this modality can capture various en face OCT biomarkers that correspond to different cell or tissue subtypes, which were previously only identified through histological or electron microscopy methods, underscoring the significance of this technique in providing valuable pathoanatomical information. In this comprehensive review, we will systematically summarize the en face OCT findings across a broad spectrum of retinal diseases, including disorders of the vitreoretinal interface and retinal vascular system (e.g. paracentral acute middle maculopathy or PAMM and diabetic retinopathy), in addition to the en face OCT features of other conditions such as age-related macular degeneration, pachychoroid disease spectrum, myopic degeneration, uveitis and inflammatory disorders, inherited retinal dystrophies, and drug toxicity. We will discuss and highlight the unique clinical and pathoanatomical findings uncovered with en face OCT of each these diseases mentioned above.},
}
@article {pmid40054506,
year = {2025},
author = {Dai, M and Du, P and Li, Y and Wang, X and Chen, J and Liu, H and Zhang, W and Zhou, J and Li, X and Wang, Y},
title = {Peptide-based hydrogel co-assembled with antibody-drug for enhanced retinal cell uptake and attenuated experimental autoimmune uveitis.},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V},
volume = {210},
number = {},
pages = {114691},
doi = {10.1016/j.ejpb.2025.114691},
pmid = {40054506},
issn = {1873-3441},
mesh = {Animals ; *Uveitis/drug therapy/immunology ; *Hydrogels/chemistry ; Retinal Pigment Epithelium/drug effects/metabolism ; *Peptides/chemistry ; Drug Delivery Systems/methods ; Mice ; Disease Models, Animal ; *Autoimmune Diseases/drug therapy/immunology ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Intravitreal Injections ; Blood-Retinal Barrier/drug effects/metabolism ; Retina/drug effects/metabolism ; Interleukin-17/immunology/antagonists &amp; inhibitors ; Apoptosis/drug effects ; *Antibodies, Monoclonal/administration &amp; dosage ; },
abstract = {Effective treatment of chronic posterior ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration requires improvements in targeted drug delivery strategies. This study introduces a novel injectable drug delivery system co-assembled with a peptide-based hydrogel and secukinumab (SEK), an IL-17A neutralising monoclonal antibody, targeting retinal pigmented epithelium (RPE) cells. Compared to a SEK solution, the SEK loaded hydrogel significantly enhanced the protein uptake (3.7 times higher) by RPE cells in an inflammatory state after 24 hours of treatment and increased the drug concentration in retinal tissues during 20 days of treatment. A single intravitreal injection of the SEK loaded hydrogel effectively suppressed inflammation in a uveitis model. It also reduced the immunoreactivity of microglia and T helper 17 cells, preserved the integrity of the blood-retina barrier, mitigated retinal cell apoptosis, and facilitated the recovery of the retinal function. This delivery system comprising an antibody-drug co-assembled with a peptide-based hydrogel shows promising potential for targeting the retina and treating complex chronic posterior ocular diseases.},
}
@article {pmid40053038,
year = {2025},
author = {Li, J and Ren, Y and Li, H and Zheng, Z},
title = {Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration.},
journal = {Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica},
volume = {58},
number = {},
pages = {e14187},
pmid = {40053038},
issn = {1414-431X},
mesh = {*T-Lymphocytes, Regulatory/metabolism ; *rac1 GTP-Binding Protein/metabolism ; Humans ; Animals ; *Choroidal Neovascularization/metabolism/immunology/pathology ; Male ; *Cytokines/metabolism ; Disease Models, Animal ; Female ; *Wet Macular Degeneration/metabolism/immunology ; Aged ; Mice ; Case-Control Studies ; Coculture Techniques ; Endothelial Cells/metabolism ; Interleukin-10/metabolism ; Transforming Growth Factor beta1/metabolism ; Middle Aged ; Signal Transduction ; },
abstract = {Age-related macular degeneration (AMD), particularly the wet form characterized by choroidal neovascularization, is a leading cause of vision loss. Dysregulation of regulatory T cells (Tregs), key modulators of inflammatory responses, may contribute to wet AMD pathogenesis. This study explored the involvement of Tregs and the Rac1 signaling pathway in modulating Treg-derived cytokine expression and their role in choroidal neovascularization during wet AMD progression. Peripheral blood samples from healthy controls, dry AMD patients, and wet AMD patients were collected. An in vitro transmembrane co-culture system of Tregs and human choroidal endothelial cells (HCECs) was employed to investigate the impact of Tregs (with or without Rac1 silencing) on the angiogenic phenotype of HCECs. A mouse model of AMD was established to evaluate the effects of a Rac1 inhibitor and IL-10/TGF-β neutralization on Tregs and choroidal neovascularization. An increased Treg percentage in the CD4+ T lymphocyte population was found in the peripheral blood samples of wet AMD patients. Tregs from wet AMD patients showed an increased expression of Rac1 and an elevated production of IL-10 and TGF-β1. Rac1 silencing suppressed Treg stability and differentiation, and impaired the pro-angiogenic effect of Tregs on HCECs. In the animal model of AMD, the administration of a Rac1 inhibitor or neutralizing antibodies against IL-10/TGF-β1 reduced Treg abundance and attenuated choroidal neovascularization. Rac1 upregulation in Tregs promoted IL-10 and TGF-β1 production to mediate choroidal neovascularization in wet AMD. Targeting Rac1 and Treg-derived IL-10/TGF-β1 production in Tregs may serve as a strategy to ameliorate AMD progression.},
}
@article {pmid40051895,
year = {2025},
author = {Wei, Q and Chi, L and Li, M and Qiu, Q and Liu, Q},
title = {Practical Applications of Artificial Intelligence Diagnostic Systems in Fundus Retinal Disease Screening.},
journal = {International journal of general medicine},
volume = {18},
number = {},
pages = {1173-1180},
pmid = {40051895},
issn = {1178-7074},
abstract = {PURPOSE: This study aims to evaluate the performance of a deep learning-based artificial intelligence (AI) diagnostic system in the analysis of retinal diseases, assessing its consistency with expert diagnoses and its overall utility in screening applications.<br><br>METHODS: A total of 3076 patients attending our hospital underwent comprehensive ophthalmic examinations. Initial assessments were performed using the AI, the Comprehensive AI Retinal Expert (CARE) system, followed by thorough manual reviews to establish final diagnoses. A comparative analysis was conducted between the AI-generated results and the evaluations by senior ophthalmologists to assess the diagnostic reliability and feasibility of the AI system in the context of ophthalmic screening.<br><br>RESULTS: : The AI diagnostic system demonstrated a sensitivity of 94.12% and specificity of 98.60% for diabetic retinopathy (DR); 89.50% sensitivity and 98.33% specificity for age-related macular degeneration (AMD); 91.55% sensitivity and 97.40% specificity for suspected glaucoma; 90.77% sensitivity and 99.10% specificity for pathological myopia; 81.58% sensitivity and 99.49% specificity for retinal vein occlusion (RVO); 88.64% sensitivity and 99.18% specificity for retinal detachment; 83.33% sensitivity and 99.80% specificity for macular hole; 82.26% sensitivity and 99.23% specificity for epiretinal membrane; 94.55% sensitivity and 97.82% specificity for hypertensive retinopathy; 83.33% sensitivity and 99.74% specificity for myelinated fibers; and 75.00% sensitivity and 99.95% specificity for retinitis pigmentosa. Additionally, the system exhibited notable performance in screening for other prevalent conditions, including DR, suspected glaucoma, suspected glaucoma, pathological myopia, and hypertensive retinopathy.<br><br>CONCLUSIONS: : The AI-assisted screening system exhibits high sensitivity and specificity for a majority of retinal diseases, suggesting its potential as a valuable tool for screening practices. Its implementation is particularly beneficial for grassroots and community healthcare settings, facilitating initial diagnostic efforts and enhancing the efficacy of tiered ophthalmic care, with important implications for broader clinical adoption.},
}
@article {pmid40051780,
year = {2025},
author = {Samacá-Samacá, D and Robles, A and Ocampo, H and Rodríguez, FJ and Sardi-Correa, C and Prieto-Pinto, L and Bührer, C and Tamayo, C and Rodríguez, D and Hernández-Quintana, M},
title = {Cost-Effectiveness and Budget Impact Analysis of the Use of Faricimab in Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration in Colombia.},
journal = {Journal of health economics and outcomes research},
volume = {12},
number = {1},
pages = {97-105},
pmid = {40051780},
issn = {2327-2236},
abstract = {Background: Retinal diseases are major contributors to disability, significantly affecting patients' quality of life. Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) represent a significant disease and economic burden in Colombia. Assessing the economic evaluation of available treatments is essential for the efficient allocation of healthcare resources. Objective: To estimate the cost-effectiveness and budget impact of using faricimab for the treatment of patients with DME and nAMD within the Colombian health system. Methods: This study used a 25-year Markov cohort model to estimate the cost-effectiveness of faricimab vs aflibercept, ranibizumab, and brolucizumab. We used the methodological guidelines of the local health technology assessment agency for conducting the cost-effectiveness and budget impact analysis. Transition probabilities and injection frequencies were derived from the literature. Drug prices were retrieved from public local databases. Quality-adjusted life years (QALYs) were assessed. The potential patient population for the budget impact analysis was estimated based on disease prevalence and expert consultations. Results: Faricimab treat-and-extend (T&amp;E) was dominant vs aflibercept T&amp;E (+0.22 QALYs), ranibizumab T&amp;E (+0.55 QALYs), and brolucizumab for 8 to 12 weeks (+0.06 QALYs) in DME, generating cost savings (in US dollars) of 3849 , 1375, and 2824 , r e s p e c t i v e l y . I n n A M D , f a r i c i m a b a l s o s h o w e d d o m i n a n c e v s a f l i b e r c e p t a s n e e d e d (+ 0.12 Q A L Y s) , r a n i b i z u m a b a s n e e d e d (+ 0.05 Q A L Y s) , a n d b r o l u c i z u m a b 8 t o 12 w e e k s (+ 0.12 Q A L Y s) w i t h s a v i n g s i n (U S) 7223, 5792 , a n d 6798, respectively. Assuming an annual market share increase for faricimab of 15% for DME and 13% for nAMD, the Colombian Health System could save 144 m i l l i o n o v e r 3 y e a r s . O f t h e s e s a v i n g s , 122.7 million are attributed to drug costs and 21.3 m i l l i o n t o a d m i n i s t r a t i o n c o s t s (U S 1 = Col$4325). Conclusion: Considering a willingness to pay threshold of $5988 per additional QALY, faricimab is a cost-effective alternative for both DME and nAMD for the Colombian healthcare system, showing dominance over other anti-vascular endothelial growth factor agents. Faricimab provides better health outcomes at lower costs vs other treatments.},
}
@article {pmid40049333,
year = {2025},
author = {Fenwick, EK and Man, REK and Tan, ACS and Najjar, RP and Milea, D and Lee, EPX and Wong, TY and Tan, GSW and Chan, HW and Laude, A and Teo, KYC and Lee, SY and Yeo, IYS and Mathur, R and Cheung, GCM and Lamoureux, EL},
title = {Psychometric evaluation and computerized adaptive testing simulations of age-related macular degeneration quality of life item banks.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {14},
number = {2},
pages = {100178},
doi = {10.1016/j.apjo.2025.100178},
pmid = {40049333},
issn = {2162-0989},
mesh = {Humans ; *Psychometrics/methods ; *Quality of Life/psychology ; *Macular Degeneration/psychology ; Cross-Sectional Studies ; Male ; Female ; Aged ; Surveys and Questionnaires ; Middle Aged ; *Computer Simulation ; Activities of Daily Living ; Aged, 80 and over ; },
abstract = {PURPOSE: To optimize the psychometric properties of age-related macular degeneration (AMD) quality of life (QoL) item banks (IBs), and evaluate their performance using computerized adaptive testing (CAT) simulations.<br><br>DESIGN: Cross-sectional, clinical study.<br><br>METHODS: 261 AMD patients answered 219 items within seven IBs: Activity Limitation (AL); Lighting (LT); Mobility (MB); Emotional (EM); Concerns (CN); AMD Management (AM); and Work (WK), referred to collectively as "MacCAT". The psychometric properties of each IB (e.g. measurement precision; item "fit"; differential item functioning (DIF)) were assessed using Rasch analysis. The mean number of items required for "high" and "moderate" measurement precision was determined using CAT simulations.<br><br>RESULTS: Of the 261 participants (mean age 70.5&#x202f;&#xb1;&#x202f;7.6 years), 69 (26.4&#x202f;%), 35 (13.4&#x202f;%), 80 (30.7&#x202f;%) and 77 (29.5&#x202f;%) had no, early, intermediate and late AMD (better eye), respectively. AL, EM, CN and AM displayed good psychometric properties overall after collapsing response categories and deleting items for misfit and/or DIF. Despite similar reengineering efforts, LT and MB had suboptimal measurement precision but were retained due to otherwise good psychometric performances. Owing to unresolvable psychometric issues, WK was not considered further. Targeting for all IBs was suboptimal. In CAT simulations on the six remaining IBs, the mean number of items required per IB ranged from 8 (AL) to 13 (MB) for moderate, and 13 (AL) to19 (MB) for high measurement precision.<br><br>CONCLUSIONS: Six IBs demonstrated acceptable psychometric properties and potential CAT efficiency, suggesting MacCAT provides a comprehensive measurement of the QoL impact of AMD and associated treatments. Further testing in larger clinical cohorts is needed.},
}
@article {pmid40048436,
year = {2025},
author = {Çevik, M&#xd6; and Mert Altuntaş, Z and Çevik, SG},
title = {Indications of the SERPINE 1 variant rs1799768's role in anti-VEGF therapy resistance in neovascular age-related macular degeneration.},
journal = {PloS one},
volume = {20},
number = {3},
pages = {e0317511},
pmid = {40048436},
issn = {1932-6203},
mesh = {Humans ; *Plasminogen Activator Inhibitor 1/genetics ; Female ; Male ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/drug therapy ; Aged, 80 and over ; *Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; *Drug Resistance/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a retinal disease prevalent in the elderly population, with two main subtypes: dry (non-exudative) and neovascular (wet or exudative). Neovascular AMD (nAMD) has a more debilitating prognosis than dry AMD, making it the third leading cause of blindness. Intravitreal injections of anti-vascular endothelial growth factor (IV anti-VEGF) are the most effective and widely accepted treatment for nAMD. However, a significant number of nAMD patients exhibit suboptimal responses to IV anti-VEGF therapy, with the underlying mechanisms not yet fully understood. We hypothesized that genetic polymorphisms associated with blood hypercoagulation may also contribute to suboptimal responses to IV anti-VEGF therapy. This study recruited 20 nAMD patients, who were divided into two groups based on their treatment responses after four years: 10 patients with suboptimal responses to IV anti-VEGF therapy and 10 patients with optimal responses. After obtaining institutional ethics board approval, we retrospectively evaluated relevant clinical records of twenty patients diagnosed with nAMD. Patient clinical data were accessed between 20th March 2021 -1st April 2021 for research purposes only. We genotyped peripheral blood DNA from each patient for hypercoagulation-related polymorphisms, including Factor V Leiden (rs6025), prothrombin c.20210G>A (rs1799963), MTHFR A1298C (rs1801131), MTHFR C677T (rs1801133), and SERPINE 1 (PAI-1-675 4G/5G) (rs1799768), and statistically compared the frequencies. Heterozygous and homozygous mutations in the SERPINE1 gene specifically PAI-1 promoter region PAI-1-675 4G/5G (rs1799768) were identified as risk factors for resistance to IV anti-VEGF therapy in nAMD patients (χ[2] test, p = 0.006). No other polymorphisms of the above-mentioned genes were statistically significant (p > 0.05). The failure of IV anti-VEGF therapy in nAMD patients may be influenced by various factors, one of which may be the inherited PAI-1-675 4G/5G (rs1799768) polymorphisms which normally known to contribute hypercoagulation. Further research involving a larger cohort is necessary to uncover the interplay between hereditary factors and other elements contributing to the inefficacy of IV anti-VEGF therapy in nAMD.},
}
@article {pmid40048184,
year = {2025},
author = {Shaw, EM and Anderson, DM and Periasamy, R and Schey, KL and Curcio, CA and Lipinski, DM},
title = {Porcine Sub-Retinal Pigment Epithelium Deposits: A Model for Dry Age-Related Macular Degeneration With Comparison to Human Drusen.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {3},
pages = {18},
pmid = {40048184},
issn = {1552-5783},
mesh = {Animals ; Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Swine ; *Retinal Drusen/metabolism/pathology ; Aged, 80 and over ; *Disease Models, Animal ; *Geographic Atrophy/metabolism/pathology ; Eye Proteins/metabolism ; Immunohistochemistry ; Glycoproteins/metabolism ; Macular Degeneration/metabolism/pathology ; Mass Spectrometry ; },
abstract = {PURPOSE: Due to the slowly progressing nature of age-related macular degeneration (AMD) and critical differences in ocular anatomy between humans and animals, it has been difficult to model disease progression, hampering the development of novel therapeutics aimed at impacting drusen biogenesis. To determine whether "drusen-in-a-dish" model systems are of utility in screening potential therapeutics aimed at early-intermediate dry AMD, we developed a detailed characterization of the protein, glycoprotein, and lipid composition of sub-retinal pigment epithelium (RPE) deposits grown by monolayers of ex vivo porcine RPE with human drusen in AMD globes.<br><br>METHODS: Immunohistochemistry and imaging mass spectrometry (IMS) were performed on 20-week aged monolayers of porcine RPE and human donor globes recovered from an 81-year-old non-transplant donor with confirmed diagnosis of bilateral dry AMD. The presence of major protein, glycoprotein, and lipid species was compared between porcine sub-RPE deposits and human drusen with reference to macular/peripheral eccentricity.<br><br>RESULTS: The protein and glycoprotein composition of porcine sub-RPE deposits closely mimics human drusen identified in donor globes with dry AMD, including the presence of major complement components (C9, CFH, CHI), apolipoproteins (ApoE, ApoJ), extracellular matrix proteins (vitronectin, collagen VI), and calcification (hydroxyapatite). Sub-RPE deposits were additionally rich in long-chain ceramide species (Cer, CerPE, PI), which have only recently been described in human drusen.<br><br>CONCLUSIONS: Due to their compositional similarity to human drusen, ex vivo "drusen-in-a-dish" systems represent a potentially robust and cost-effective model for both studying the pathobiology of drusen biogenesis and screening novel therapeutics aimed at limiting drusen formation.},
}
@article {pmid40047030,
year = {2025},
author = {Smolin, SA and Stoyukhina, AS},
title = {[Choroidal neovascularization associated with choroidal nevi].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {1},
pages = {104-112},
doi = {10.17116/oftalma2025141011104},
pmid = {40047030},
issn = {0042-465X},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnosis/etiology/drug therapy ; *Choroid Neoplasms/complications/diagnosis ; *Choroid/pathology/blood supply ; Diagnosis, Differential ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/therapeutic use ; Fundus Oculi ; *Nevus, Pigmented/complications/diagnosis ; },
abstract = {Choroidal neovascularization (CNV) is a pathological angiogenic process observed in various fundus diseases, including choroidal nevi. This article reviews key information on the pathogenesis of CNV associated with choroidal nevi, examines diagnostic methods using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A), including modern classifications and criteria for assessing disease activity. The article also discusses approaches to the differential diagnosis of nevi combined with neovascular age-related macular degeneration, progressive nevi, and melanomas, and analyzes the features of treatment with antiangiogenic agents and their effects on pigmented choroidal lesions.},
}
@article {pmid40047020,
year = {2025},
author = {Jatoi, A},
title = {[Association between integrity of foveal photoreceptors and ultimate visual outcome in neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {1},
pages = {32-36},
doi = {10.17116/oftalma202514101132},
pmid = {40047020},
issn = {0042-465X},
mesh = {Humans ; *Visual Acuity ; Male ; Tomography, Optical Coherence/methods ; Female ; Aged ; *Fovea Centralis/pathology/diagnostic imaging ; Retrospective Studies ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/diagnosis/physiopathology/drug therapy ; *Macular Degeneration/diagnosis/physiopathology ; },
abstract = {PURPOSE: This study investigates the clinical features and outcome dimensions of neovascular age-related macular degeneration (nAMD).<br><br>MATERIAL AND METHODS: This retrospective study analyzed 80 subjects diagnosed with nAMD. The patients received successful treatment through intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) agents. The subjects were classified into three groups based on the final integrity of their inner segment/outer segment (IS/OS) layer of the retina, assessed using spectral-domain optical coherence tomography (SD-OCT). This classification helped to understand the extent of retinal damage and the progression of nAMD. The primary evaluation was to examine the association between final IS/OS integrity and final visual acuity in the groups. The study also evaluated foveal microstructures (choroidal neovascularization size, external limiting membrane, outer nuclear layer thickness, and central macular thickness) at the initial and final visits, and their relationships with final IS/OS integrity.<br><br>RESULTS: The study found a significant association (P<0.001) between final visual acuity and IS/OS integrity. The V group had the best visual acuity (0.12&#xb1;0.09) compared to the P group (0.39&#xb1;0.45) and I group (0.92&#xb1;0.42). Improved visual acuity was strongly correlated with less disrupted IS/OS and ELM. Intact photoreceptor integrity was linked to preserved IS/OS and ELM, thinner CMT, and shorter CNV height before treatment. However, photoreceptor integrity was not significantly correlated with CMT, RPE regularity, or ONL thickness at the final examination, suggesting it may be independently affected by nAMD.<br><br>CONCLUSION: Final visual acuity in nAMD patients post-treatment was strongly linked to foveal photoreceptor integrity. Photoreceptor integrity correlated with initial visual acuity, CMT, ELM integrity, CNV height, and IS/OS layer integrity. These factors can predict visual outcomes after resolution of exudaiton.},
}
@article {pmid40042510,
year = {2025},
author = {Strobl, EV and Gamazon, E},
title = {Discovering root causal genes with high-throughput perturbations.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {40042510},
issn = {2050-084X},
support = {R01 HG011138/HG/NHGRI NIH HHS/United States ; R35 HG010718/HG/NHGRI NIH HHS/United States ; R35HG010718/HG/NHGRI NIH HHS/United States ; R01HG011138/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/genetics ; *Multiple Sclerosis/genetics ; Algorithms ; Gene Expression Profiling ; Sequence Analysis, RNA/methods ; RNA-Seq ; High-Throughput Nucleotide Sequencing ; Single-Cell Analysis ; },
abstract = {Root causal gene expression levels - or root causal genes for short - correspond to the initial changes to gene expression that generate patient symptoms as a downstream effect. Identifying root causal genes is critical towards developing treatments that modify disease near its onset, but no existing algorithms attempt to identify root causal genes from data. RNA-sequencing (RNA-seq) data introduces challenges such as measurement error, high dimensionality and non-linearity that compromise accurate estimation of root causal effects even with state-of-the-art approaches. We therefore instead leverage Perturb-seq, or high-throughput perturbations with single-cell RNA-seq readout, to learn the causal order between the genes. We then transfer the causal order to bulk RNA-seq and identify root causal genes specific to a given patient for the first time using a novel statistic. Experiments demonstrate large improvements in performance. Applications to macular degeneration and multiple sclerosis also reveal root causal genes that lie on known pathogenic pathways, delineate patient subgroups and implicate a newly defined omnigenic root causal model.},
}
@article {pmid40041652,
year = {2025},
author = {Elghazali Bakhiet, T and Hassan, S and Shankar, J},
title = {Paediatric Choroidal Neovascularisation of Unknown Cause.},
journal = {Cureus},
volume = {17},
number = {2},
pages = {e78381},
pmid = {40041652},
issn = {2168-8184},
abstract = {Choroidal neovascularisation (CNV) is a condition characterised by the proliferation of abnormal blood vessels within the choroid. These vessels tend to leak blood and fluid into the adjacent tissues, thereby causing harm to the retina and posing a threat to visual function. The infrequency of CNV in children can be attributed to its predominant association with age-related macular degeneration (AMD). The incidence of CNV in paediatric patients is generally considered to be very low, with rates often cited as being less than one case per 100,000 individuals annually. We present a 10-year-old female who was referred by an optician due to a one-month history of unilateral blurred vision in her left eye, leading to difficulties in reading the school board. The patient had no other past medical, trauma, or ocular history, and her family and developmental history were non-significant. On examination, the patient's visual acuity measured 6/6 in the right eye and 6/9 in the left eye. Initial dilated fundal examination revealed a yellow hypopigmented, raised subfoveal lesion with irregular borders in her left eye; however, there was no evidence of neovascularisation or haemorrhage. The patient presented two weeks later with a sudden visual drop of 6/60. Fundal examination showed a new haemorrhage in the left eye, and subretinal fluid (SRF) was noted within the macula. Optical coherence tomography (OCT) and OCT angiography (OCT-A) identified an increase in SRF and confirmed a solitary CNV. The child received three loading doses of intravitreal anti-vascular endothelial growth factor (anti-VEGF) at one-month intervals, leading to complete resolution of SRF and haemorrhage on OCT. Consequently, the patient's visual acuity improved to 6/12. In summary, idiopathic CNV, although rare in paediatric patients, must be promptly diagnosed and adequately treated to guarantee resolution.},
}
@article {pmid40040560,
year = {2025},
author = {Wang, H and Bahrami, B and Huang, S and Tahmasebi Sarvestani, M and Cugati, S and Lake, S and Chan, WO and Supramaniam, D and Little, M},
title = {Safety of an Intravitreal Bevacizumab Biosimilar (MVASI).},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {5},
pages = {523-528},
pmid = {40040560},
issn = {1442-9071},
mesh = {Humans ; *Bevacizumab/administration &amp; dosage/adverse effects ; Intravitreal Injections ; Retrospective Studies ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Male ; Female ; *Biosimilar Pharmaceuticals/administration &amp; dosage/adverse effects ; Middle Aged ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Retinal Vein Occlusion/drug therapy ; },
abstract = {BACKGROUND: Intravitreal bevacizumab has been used off-label to treat multiple ocular conditions for almost two decades. Reference bevacizumab, Avastin, was discontinued in Australia in 2021. A bevacizumab biosimilar, MVASI, was approved by the Therapeutic Goods Administration for the treatment of metastatic cancer in 2020. There is limited safety data for the off-label intravitreal use of MVASI. This retrospective study evaluates the safety of intravitreal MVASI.<br><br>METHODS: Retrospective review of all eyes that were given intravitreal MVASI at all metropolitan public hospitals in South Australia between 1st May 2022 and 30th May 2024. Demographic data, injection indications, number of injections per eye, whether patients were switched to another agent, and associated complications were collected from electronic and paper medical records.<br><br>RESULTS: A total of 6230 injections were given to 1682 eyes in this study. The mean age of the study population was 69.8&#x2009;&#xb1;&#x2009;15.6&#x2009;years. The overall mean number of MVASI injections given per eye was 3.7&#x2009;&#xb1;&#x2009;2.9 (range 1-21). The indications for treatment were neovascular age-related macular degeneration (2106 injections; 33.8%), diabetic macular oedema (1634 injections; 26.2%), branch retinal vein occlusion (695 injections; 11.2%), proliferative diabetic retinopathy (596 injections; 9.6%), central retinal vein occlusion (558 injections; 9.0%) and other (641 injections; 10.3%). Significant sight-threatening complications included 3 cases of bacterial endophthalmitis (0.05%) and 3 cases of uveitis (0.05%). No cases of retinal vasculitis were observed.<br><br>CONCLUSIONS: Intravitreal MVASI had a similar ophthalmic safety profile and may be used as an alternative to Avastin.},
}
@article {pmid40039913,
year = {2024},
author = {Matta, S and Lamard, M and Borderie, L and Le Guilcher, A and Massin, P and Rottier, JB and Cochener, B and Quellec, G},
title = {Domain Generalization for Multi-disease Detection in Fundus Photographs.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2024},
number = {},
pages = {1-4},
doi = {10.1109/EMBC53108.2024.10781556},
pmid = {40039913},
issn = {2694-0604},
mesh = {Humans ; Algorithms ; *Photography/methods ; *Fundus Oculi ; Machine Learning ; Image Processing, Computer-Assisted/methods ; },
abstract = {Domain generalization (DG) is a paradigm ensuring machine learning algorithms predict well on unseen domains. Recent computer vision research in DG highlighted how inconsistencies in datasets, architectures, and model criteria challenge fair comparisons. In the medical domain, the application of DG algorithms assumes an even more challenging task as medical data often exhibit significant variability due to diverse imaging modalities, patient demographics, and disease characteristics. In light of this, DG algorithms need to generalize effectively across different medical settings and patient populations for ensuring robustness and fairness in healthcare applications. In this paper, we evaluate various DG algorithms and strategies for the application of multi-disease detection in fundus photographs. We conducted extensive experiments using four heterogeneous datasets: OPHDIAT (France, diabetic population), OphtaMaine (France, general population), RIADD (India, general population) and ODIR (China, general population). The following diseases were targeted: diabetes, glaucoma, cataract, age-related macular degeneration, hypertension, myopia and other diseases/abnormalities.},
}
@article {pmid40039366,
year = {2024},
author = {Ning, Z and Xu, Y and Li, C and Hao, Y and Ning, Z and Liu, C and Yan, K},
title = {Channel Fitting Network for Retinal Lesion Segmentation from OCT Images.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2024},
number = {},
pages = {1-6},
doi = {10.1109/EMBC53108.2024.10782850},
pmid = {40039366},
issn = {2694-0604},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Neural Networks, Computer ; *Retina/diagnostic imaging/pathology ; *Image Processing, Computer-Assisted/methods ; Algorithms ; Macular Degeneration/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; },
abstract = {Retinal lesion is a cause of age-related macular degeneration that poses a big threat to elderly population. The accurate detection and segmentation of retinal lesions benefits the early diagnosis of age-related macular degeneration and monitoring of disease progression. However, due to the large variant of imaging characteristics among different subtypes of diseases, it is challenging for a model to precisely segment retinal lesions. On the other hand, with the usage of deep neural networks (DNN), the accuracy of classifying subtypes of the retinal disease is high, which proves that the imaging features extracted from the classification models are more accurate and useful than the features obtained from segmentation models. Inspired by it, we propose a channel fitting module to enhance feature maps of segmentation model, with guidance of classification model. After the channel fitting, those feature maps that incorrectly emphasize irrelevant regions are filtered out. Therefore, our segmentations are more accurate to reflect true lesion regions. We conducted five-fold cross validation on 2633 retinal images scanned from 164 patients, proving the effectiveness and superiority of the proposed model.},
}
@article {pmid40038967,
year = {2024},
author = {Zhang, H and Heinke, A and Broniarek, K and Galang, CMB and Deussen, DN and Nagel, ID and Michalska-Malecka, K and Bartsch, DG and Freeman, WR and Nguyen, TQ and An, C},
title = {OCTA-based AMD Stage Grading Enhancement via Class-Conditioned Style Transfer.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2024},
number = {},
pages = {1-5},
pmid = {40038967},
issn = {2694-0604},
support = {R01 EY033847/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/diagnosis ; *Tomography, Optical Coherence/methods ; Neural Networks, Computer ; Algorithms ; *Angiography/methods ; },
abstract = {Optical Coherence Tomography Angiography (OCTA) is a promising diagnostic tool for age-related macular degeneration (AMD), providing non-invasive visualization of sub-retinal vascular networks. This research explores the effectiveness of deep neural network (DNN) classifiers trained exclusively on OCTA images for AMD diagnosis. To address the challenge of limited data, we combine OCTA data from two instruments-Heidelberg and Optovue-and leverage style transfer technique, CycleGAN, to convert samples between these domains. This strategy introduces additional content into each domain, enriching the training dataset and improving classification accuracy. To enhance the CycleGAN for downstream classification tasks, we propose integrating class-related constraints during training, which can be implemented in either supervised or unsupervised manner with a pretrained classifier. The experimental results demonstrate that the proposed class-conditioned CycleGAN is effective and elevates DNN classification accuracy in both OCTA domains.},
}
@article {pmid40037467,
year = {2025},
author = {Sarvepalli, SM and Kapoor, I and Sarici, K and Garg, SJ and Hadziahmetovic, M},
title = {Evaluating photodynamic therapy as an adjuvant treatment for neovascular AMD: A comprehensive meta-analysis.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {14},
number = {2},
pages = {100173},
doi = {10.1016/j.apjo.2025.100173},
pmid = {40037467},
issn = {2162-0989},
mesh = {Humans ; *Photochemotherapy/methods ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Bevacizumab/administration &amp; dosage/therapeutic use ; Receptors, Vascular Endothelial Growth Factor ; Ranibizumab/administration &amp; dosage/therapeutic use ; Recombinant Fusion Proteins ; },
abstract = {PURPOSE: This study aimed to assess the role of photodynamic therapy (PDT) as an adjunct to anti-vascular endothelial growth factor (Anti-VEGF) intravitreal injections in the treatment of neovascular age-related macular degeneration (nvAMD).<br><br>METHODS: PubMed, Cochrane Library, and ClinicalTrials.gov were searched for keywords "macular degeneration" and "photodynamic therapy" and "placebo" or "ranibizumab" or "bevacizumab" or "aflibercept" from inception to 2023. Included studies were peer-reviewed primary data reporting 12-month treatment results of nvAMD with anti-VEGF and PDT, anti-VEGF alone, intravitreal triamcinolone, or placebo. 23 studies were included in the final analysis. The major outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT), and injection burden at 12 months.<br><br>RESULTS: Anti-VEGF +&#x202f;PDT had better BCVA at 12 months compared to anti-VEGF (MD -0.07; 95&#x202f;% CI -0.12, -0.01; P&#x202f;=&#x202f;0.02). There was no significant difference in CRT at 12 months in anti-VEGF +&#x202f;PDT group versus anti-VEGF (MD -3.66; 95&#x202f;% CI -10.28, 2.98; P&#x202f;=&#x202f;0.28). Anti-VEGF +&#x202f;PDT group had significantly fewer injections compared to anti-VEGF (MD -1.76; 95&#x202f;% CI -1.95, -1.58; P&#x202f;<&#x202f;0.0001). There was no significant difference in pooled ocular adverse events between anti-VEGF +&#x202f;PDT versus anti-VEGF (MD 0.96; 95&#x202f;% CI 0.68, 1.36; P&#x202f;=&#x202f;0.41).<br><br>CONCLUSIONS: PDT is a successful adjunctive to anti-VEGF injections for the treatment of nvAMD. The combination of the therapies leads to improved BCVA at 12 months, decreased injection burden, and no difference in ocular safety.},
}
@article {pmid40035725,
year = {2025},
author = {Larbi, D and Rief, AM and Kang, S and Chen, S and Batsuuri, K and Fuhrmann, S and Viswanathan, S and Wohl, SG},
title = {Dicer Loss in Müller Glia Leads to a Defined Sequence of Pathological Events Beginning With Cone Dysfunction.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {3},
pages = {7},
pmid = {40035725},
issn = {1552-5783},
support = {R01 EY014954/EY/NEI NIH HHS/United States ; R01 EY024373/EY/NEI NIH HHS/United States ; R01 EY032532/EY/NEI NIH HHS/United States ; R21 EY032724/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Ribonuclease III/genetics ; Electroretinography ; Tomography, Optical Coherence ; Mice ; Mice, Knockout ; *DEAD-box RNA Helicases/genetics ; *Retinal Cone Photoreceptor Cells/pathology ; *Ependymoglial Cells/pathology/metabolism/enzymology ; Retinal Pigment Epithelium/pathology ; Disease Models, Animal ; *Retinal Degeneration/pathology/physiopathology ; MicroRNAs/genetics ; },
abstract = {PURPOSE: The loss of Dicer in Müller glia (MG) results in severe photoreceptor degeneration, as it occurs in retinitis pigmentosa or age-related macular degeneration; however, the sequence of events leading to this severe degenerative state is unknown. The aim of this study was to conduct a chronological functional and structural characterization of the pathological events in MG-specific Dicer-conditional knockout (cKO) mice in vivo and histologically.<br><br>METHODS: To delete Dicer and mature microRNAs (miRNAs) in MG, two conditional Dicer1 knockout mouse strains (Rlbp-CreER:tdTomato:Dicer-cKOMG and Glast-CreER:tdTomato:Dicer-cKOMG) were created. Optical coherence tomography (OCT), electroretinograms (ERGs), and histological analyses were conducted to investigate structural and functional changes up to 6 months after Dicer deletion.<br><br>RESULTS: Dicer/miRNA loss in MG leads to (1) impairments of the area spanning from the external limiting membrane (ELM) to the retinal pigment epithelium (RPE), (2) cone photoreceptor dysfunction, and (3) retinal remodeling and functional loss of the inner retina at 1, 3, and 6&#xa0;months after Dicer loss, respectively, in both of the knockout mouse strains. Furthermore, in the Rlbp-CreER:tdTomato:Dicer-cKOMG strain, rod photoreceptor impairment was found 4&#xa0;months after Dicer depletion (4) accompanied by alteration of RPE integrity (5).<br><br>CONCLUSIONS: MG Dicer loss in the adult mouse retina impacts cone function prior to any measurable changes in rod function, suggesting a pivotal role for MG Dicer and miRNAs in supporting cone health. A partially impaired RPE, however, seems to accelerate rod degeneration and overall degenerative events.},
}
@article {pmid40034025,
year = {2025},
author = {Lee, J and Kim, YJ and Lee, K and Kim, YK and Rhee, TG and Shim, SR and Kim, JH},
title = {Pentosan Polysulfate Sodium and Maculopathy in Patients with Interstitial Cystitis: A Systematic Review and Meta-Analysis.},
journal = {The world journal of men's health},
volume = {43},
number = {4},
pages = {866-874},
pmid = {40034025},
issn = {2287-4208},
support = {/SCH/Soonchunhyang University/Korea ; 2022R1A2C3005586/NRF/National Research Foundation of Korea/Korea ; },
abstract = {PURPOSE: Pentosan polysulfate sodium (PPS) is the only pharmacological intervention approved by the US Food and Drug Administration for treating interstitial cystitis (IC) to date. However, PPS may induce an adverse event, maculopathy, which can be a significant challenge. To determine the risk of PPS-induced maculopathy in patients with IC.<br><br>MATERIALS AND METHODS: PubMed and Embase were systematically searched through July 2024. Two authors also independently and manually searched all relevant studies. We included national level cohort studies using healthcare claim big data or real-world data with the following criteria: (1) patients diagnosed with IC; (2) interventions included PPS as an active treatment; (3) comparisons were specified as non-PPS interventions; and (4) the primary outcome of interest was the risk of maculopathy. The pairwise meta-analysis was performed to compare the PPS treatment group with control used in IC. The primary outcome measure was the hazard ratio (HR), odds ratio (OR), and proportional report ratio (PRR) of maculopathy after receiving the PPS treatment, as compared to non-PPS interventions.<br><br>RESULTS: A comprehensive literature search was conducted, and identified 6 studies with 411,098 patients. The pooled risk for maculopathy due to PPS in patients with IC was significant (HR, 1.678; 95% confidence interval [95% CI], 1.066-2.642]). The heterogeneity test produced a Higgins' I-squared statistic, which was 83.6%. In the subgroup analysis of follow-up period of less than 5 years (HR, 1.285; 95% CI, 1.139-1.449) and more (HR, 1.341; 95% CI, 1.307-1.375) were statistically significant, indicating that the patients with IC who had a long-term PPS treatment were more likely to have maculopathy than the control groups.<br><br>CONCLUSIONS: This is the first study to investigate the relationship between PPS and its association with the risk of maculopathy in patients with IC through a systematic review and meta-analysis.},
}
@article {pmid40030130,
year = {2025},
author = {Souied, EH and Amoroso, F and Baillif, S and Devin, F and Weber, M and Colantuono, D and Blanco-Garavito, R and Miere, A},
title = {Can changes on OCTA predict exudative activity on OCT in eyes with neovascular age related macular degeneration? The ACTOR Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004444},
pmid = {40030130},
issn = {1539-2864},
abstract = {PURPOSE: To explore the predictability of changes in neovascularization morphology on optical coherence tomography angiography (OCTA) in relation to exudative activity on structural optical coherence tomography (OCT) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg.<br><br>METHODS: Eighty-five eyes of 85 patients with nAMD, diagnosed less than 1 year prior to study entry and treated with ranibizumab 0.5 mg, were included in this longitudinal, prospective study. Included eyes had no exudative activity feature at study inclusion and were treated with ranibizumab 0.5 mg in a PRN regimen for the following 9 months. At each study visit structural OCT and OCTA were performed. Qualitative and quantitative vascular characteristics of macular neovascularization (MNV) were extracted at each visit and correlated with the presence of exudative activity on OCT.<br><br>RESULTS: No significant correlation was found between OCTA (neo)vascular characteristics in the absence of exudation with the presence of exudative activity on structural OCT the following month. OCTA's positive predictive value (PPV) for the overall population was 38.87% (confidence interval [33.8%; 44.2%]). The negative predictive value (NPV) of OCTA on the overall population was 60.92%. Inter-observer reproducibility of OCTA assessments Cohen's kappa=0.82.<br><br>CONCLUSION: While OCTA may not be predictive of imminent exudative activity in nAMD, it brings additional information on MNV flow and holds potential as a tool for understanding vascular remodeling. Neovascularization remodeling and exudation may be two separate findings in the disease process in nAMD without necessarily having a causal relationship.},
}
@article {pmid40029473,
year = {2025},
author = {Egger, D and Heger, KA and Bolz, M and Brinkmann, MP and Krepler, K and Vecsei-Marlovits, PV and Wedrich, A and Waldstein, SM},
title = {Intravitreal therapy-success stories and challenges.},
journal = {Wiener medizinische Wochenschrift (1946)},
volume = {175},
number = {7-8},
pages = {162-174},
pmid = {40029473},
issn = {1563-258X},
mesh = {Humans ; *Intravitreal Injections/economics ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Genetic Therapy ; Diabetic Retinopathy/drug therapy ; Macular Edema/drug therapy ; Cost-Benefit Analysis ; Macular Degeneration/drug therapy ; Geographic Atrophy/drug therapy ; },
abstract = {Intravitreal injections have revolutionized the treatment of various sight-threatening diseases of the posterior segment of the eye. Initially explored for treatment of bacterial endophthalmitis, intravitreal injections rapidly expanded to combat retinal vascular disease in particular. Especially anti-vascular endothelial growth factor agents have emerged as a cornerstone of intravitreal therapy, targeting neovascular age-related macular degeneration and diabetic macular edema as important examples. Advances continue, with novel therapies such as complement inhibitors now available as treatment for geographic atrophy secondary to non-neovascular age-related macular degeneration, offering hope for a previously untreatable condition. Pioneering approaches such as the port delivery system and intravitreal gene therapy aim to improve treatment efficacy while minimizing patient burden. Despite notable successes, challenges for intravitreal therapies persist, including ocular and systemic complications and high treatment burden. Future research endeavors aim to address these challenges and enhance treatment outcomes. This comprehensive review critically evaluates the efficacy, safety, and cost-effectiveness of intravitreal injections, delving into emerging trends and future directions.},
}
@article {pmid40029243,
year = {2025},
author = {Barreto, P and Farinha, C and Coimbra, R and Silva, R},
title = {Author Response: Unveiling Statins and Genetics in Age-Related Macular Degeneration Progression: What Is the Appropriate Modeling Strategy?.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {3},
pages = {3},
pmid = {40029243},
issn = {1552-5783},
}
@article {pmid40025740,
year = {2025},
author = {Zhang, W and Huang, Q and Li, J},
title = {Causal effect analysis of the relationship between Alzheimer's diseas (AD) and wet age-related macular degeneration (wAMD).},
journal = {European journal of ophthalmology},
volume = {35},
number = {4},
pages = {1376-1381},
doi = {10.1177/11206721251322219},
pmid = {40025740},
issn = {1724-6016},
mesh = {Humans ; *Alzheimer Disease/genetics/epidemiology/complications ; *Wet Macular Degeneration/genetics/epidemiology/diagnosis ; *Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Aged ; Mendelian Randomization Analysis ; Male ; Female ; Aged, 80 and over ; Risk Factors ; Genotype ; },
abstract = {PurposeAlzheimer's disease (AD) and wet age-related macular degeneration (wAMD) are both prevalent degenerative diseases in the elderly population. However, whether AD is causally related to wAMD is unclear. A Mendelian randomization(MR) analysis was conducted to investigate the association between them.MethodsSingle nucleotide polymorphisms (SNPs) involved in this study were acquired from the IEU Open Genome-wide association study (GWAS) database. As for AD (ID: finn-b-G6_ALZHEIMER), there were 3899 cases and 214,893 controls. For wAMD (ID:finn-b-WET_AMD), it contained 2114 cases and 206,601 controls. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses and Steiger test.ResultsThe occurrence of wAMD was associated with decreased risk of AD (IVW, OR was 0.82 at 95%, Confidence interval (CI) of 0.77-0.88, p = 1.67E-09).ConclusionsOur findings demonstrated a potentially protective effect of AD against the development of wAMD. It promotes further investigation of interaction between AD and wAMD.},
}
@article {pmid40025106,
year = {2025},
author = {Zhang, S and Zhang, C and Zhang, Y and Feng, Y},
title = {Unraveling the role of neuregulin-mediated astrocytes-OPCs axis in the pathogenesis of age-related macular degeneration and Parkinson's disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {7352},
pmid = {40025106},
issn = {2045-2322},
support = {2019YFC1711605//National Key Research and Development Program of China/ ; },
mesh = {*Parkinson Disease/metabolism/pathology/genetics ; *Astrocytes/metabolism/pathology ; Humans ; *Macular Degeneration/metabolism/pathology/genetics ; Signal Transduction ; *Neuregulins/metabolism/genetics ; Gene Regulatory Networks ; *Oligodendroglia/metabolism ; Retinal Ganglion Cells/metabolism/pathology ; Single-Cell Analysis ; },
abstract = {Age-related macular degeneration (AMD) and Parkinson's disease (PD) are prevalent and debilitating conditions that lead to irreversible blindness and dyskinesia, respectively. Emerging evidences imply that retinal abnormalities may serve as early indicators for monitoring PD. This study endeavors to explore the complex interactions and focus on their shared molecular and pathological mechanisms. We employed a comprehensive approach by integrating single-cell RNA sequencing (scRNA-seq) datasets, obtained from dry AMD retinas and PD brain tissues, along with Weighted Gene Co-expression Network Analysis (WGCNA)-related computational analysis. Gene Set Enrichment Analysis (GSEA) was conducted to analyze PD-related genes within retinal ganglion cells in dry AMD. Cell-cell chat was utilized to predict intercellular communication and signaling pathways. Module eigengenes (MEs) were calculated to identify specific gene modules. Dysregulation of PALLD, FYN and ZMZ1 may lead to cell structural abnormalities, impaired mitochondrial functions, and increased susceptibility to neuroinflammation, contributing to the AMD and PD progression. Additionally, this study highlighted an astrocyte-oligodendrocyte precursor cell (OPCs) signaling axis mediated by Neuregulin (NRG), which is hypothesized to influence neuroinflammatory processes characteristic of dry AMD and PD pathogenesis. Notably, ME-salmon module associated with gene dysregulation exhibited a strong positive correlation with the ME-blue module, linked to neurodegenerative impairment, and the ME-yellow module, related to mitochondrial dysfunction. The comprehensive investigation on astrocytes-OPCs signaling axis, and the NRG signaling pathway advances our understanding of the intricate biological processes underpinning AMD and PD. This research underscores the critical importance about exploring glial-related cell interactions, providing valuable insights into potential novel therapeutic approaches for these complex diseases.},
}
@article {pmid40024371,
year = {2025},
author = {Kha, R and Burlutsky, G and Thiagalingam, A and Kovoor, P and Chiha, J and Mitchell, P and Liew, G},
title = {Association between Age-Related Macular Degeneration and Mortality in a High Cardiovascular Risk Cohort: A Prospective Cohort Study.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {9},
pages = {821-827},
doi = {10.1016/j.oret.2025.02.024},
pmid = {40024371},
issn = {2468-6530},
mesh = {Humans ; Female ; Male ; Prospective Studies ; Aged ; *Cardiovascular Diseases/mortality/diagnosis ; Middle Aged ; Australia/epidemiology ; Follow-Up Studies ; Risk Factors ; *Macular Degeneration/diagnosis/complications/mortality/epidemiology ; Cause of Death/trends ; Risk Assessment/methods ; Coronary Angiography ; Survival Rate/trends ; Aged, 80 and over ; },
abstract = {OBJECTIVE: To investigate whether age-related macular degeneration (AMD) predicts the risk of all-cause and cardiovascular disease (CVD) mortality in a high CVD risk cohort.<br><br>DESIGN: Prospective cohort study.<br><br>PARTICIPANTS: A total of 1545 adult participants who presented to a tertiary Australian hospital for evaluation of acute coronary syndrome were included in this study.<br><br>METHODS: Participants were evaluated for acute coronary syndrome using coronary angiography. Participants were concurrently examined for AMD from mydriatic fundus photographs, which were graded using the Wisconsin grading system into categories of any AMD, early AMD, and late AMD. Coronary artery disease was graded from coronary angiograms using the Gensini score. Mortality data were obtained 9 years after baseline examination through data linkage with the Australian National Death Index. Hazard ratios (HRs) were obtained using Cox regression analysis.<br><br>MAIN OUTCOME MEASURES: All-cause and CVD mortality data were obtained through data linkage with the Australian National Death Index. Death rates through June 2018 were compared by demographics and potential confounders.<br><br>RESULTS: Any AMD was identified in 107 (6.9%) participants, including those with early (n = 86) and late AMD (n = 21). Over 9 years of follow-up, 234 (15.1%) participants had died, including 174 (11.3%) participants from fatal CVD events. After controlling for age, sex, body mass index, total cholesterol, smoking status, history of diabetes, hypertension, myocardial infarction, stroke, and macrovascular coronary artery disease severity using the Gensini score, there was an increased rate of all-cause mortality for those with any AMD (HR, 2.37; 95% confidence interval [CI], 1.54-3.64), early AMD (HR, 2.42; 95% CI, 1.48-3.94), and late AMD (HR, 2.25; 95% CI, 1.08-4.71). Any AMD (HR, 2.62; 95% CI, 1.61-4.26) and early AMD (HR, 2.61; 95% CI, 1.50-4.64) were also associated with a greater likelihood of CVD mortality. Late AMD was not associated with CVD mortality.<br><br>CONCLUSIONS: In individuals with high CVD risk, the presence of AMD at any stage independently predicted increased all-cause mortality. Meanwhile, any AMD and early AMD increased the risk of CVD mortality. Although mechanisms are unclear, this potentially reflects shared pathways between AMD and CVD.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid40024370,
year = {2025},
author = {Monés, J and Pagani, F and Santmaría, JF and Garcia, M and Romero, C and Garcia, D and Serrano, A and Carrasco, A},
title = {Spontaneous Soft Drusen Regression without Atrophy and the Drusen Ooze.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {9},
pages = {828-837},
doi = {10.1016/j.oret.2025.02.023},
pmid = {40024370},
issn = {2468-6530},
mesh = {Humans ; Retrospective Studies ; *Retinal Drusen/diagnosis/etiology ; Male ; Female ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Aged ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; Fundus Oculi ; Aged, 80 and over ; Remission, Spontaneous ; Middle Aged ; *Geographic Atrophy/diagnosis ; Visual Acuity ; Atrophy ; },
abstract = {OBJECTIVE: To determine the incidence of spontaneous soft drusen (SD) regression without atrophy (DRwoA) in patients with intermediate or atrophic age-related macular degeneration (AMD), evaluate associated events, and offer potential explanations.<br><br>DESIGN: A retrospective review of the imaging of a consecutive series of 640 eyes from 320 patients with AMD who had &#x2265;2 years of follow-up.<br><br>SUBJECTS: Four hundred twenty-seven eyes from 262 patients with intermediate AMD or atrophic AMD and no present or past exudative AMD.<br><br>METHODS: Retinal imaging included infrared reflectance imaging, fundus autofluorescence, spectral-domain OCT, and color fundus photography.<br><br>MAIN OUTCOME MEASURES: The outcomes included drusen regression without atrophy with integrity of the retinal pigment epithelium (RPE) and repositioning over Bruch's membrane. In addition, drusen that would collapse with atrophy (DCwA) in the same area simultaneously were named "sentinel" DCwA. The outcomes also included the reversibility of features of incomplete RPE, outer retinal atrophy (iRORA), and the areas ("halos") of DRwoA around the "sentinel" drusen.<br><br>RESULTS: Among the 427 eyes, 53 events of DRwoA were found, representing 24.17% of the eyes with SD. In 50 cases (94.33%), a "sentinel" DCwA in the vicinity was found. In 58% of the cases, a well-identifiable halo of drusen disappearance around the "sentinel" DCwA was well visible.<br><br>CONCLUSIONS: Drusen regression without atrophy is a frequently observed phenomenon linked to SD and almost invariably occurs near a "sentinel" DCwA. The coalescence of the drusen and the spatial and temporal association of the DRwoA and the DCwA strongly suggest that the drusen material of DRwoA escapes to a contiguous "sentinel" DCwA. Although the hypothesis of the disappearance of drusen material due to RPE death may explain the DCwA, it fails to account for DRwoA. Instead, the "drusen ooze" hypothesis, which posits the movement of drusen content to the subretinal space through RPE defects, may explain both the DCwA and the DRwoA. This hypothesis offers insights into the reversibility of iRORA features and suggests that therapies targeting drusen material removal before RPE disruptions could potentially prevent atrophy secondary to SD collapse.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40024365,
year = {2025},
author = {Garay-Aramburu, G and Pereira Delgado, E and López-Liroz, I and Figueras-Roca, M and López Rodríguez, I and Blanch, C},
title = {Translation and cultural adaptation of the Impact of Vision Impairment (IVI) questionnaire in Spain.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {100},
number = {4},
pages = {167-173},
doi = {10.1016/j.oftale.2025.02.002},
pmid = {40024365},
issn = {2173-5794},
mesh = {Humans ; Spain ; Cross-Sectional Studies ; Male ; Female ; Aged ; Translations ; *Quality of Life ; Middle Aged ; Surveys and Questionnaires ; Aged, 80 and over ; *Vision Disorders/etiology ; Cultural Characteristics ; *Macular Degeneration ; },
abstract = {BACKGROUND AND PURPOSES: Age-related macular degeneration (AMD) is one of the leading causes of visual acuity (VA) impairment in Europe. The assessment of the patients' vision-related quality of life (VRQoL) is critical to disease management. The Impact of Visual Impairment questionnaire (IVI) is indicated to assess VRQoL in AMD and its most severe form, neovascular AMD (nAMD). Translation and cultural adaptation of 28-item IVI questionnaire (IVI-28) to Castilian and three other co-official languages in Spain is presented.<br><br>MATERIAL AND METHODS: Observational, cross-sectional, multicentric study with two focus groups for each language: Castilian, Catalan, Galician and Basque. Translated versions of IVI-28 were administered to patients, with a subsequent comprehension test to assess the clarity and understanding of the instructions, items and response formats.<br><br>RESULTS: The Castilian version of the IVI-28 (IVI-Es) was administered to 11 patients, the Catalan version (IVI-Ca) to 12 patients, the Galician version (IVI-Ga) to 9 patients and the Basque version (IVI-Eu) to 8 patients. All versions showed good feasibility and minor changes were reported in the comprehension test.<br><br>CONCLUSIONS: The translation and adaptation of IVI-28 to Castilian, Catalan, Galician and Basque is the first step for its use in nAMD population and for the clinical management of this disease in Spain.},
}
@article {pmid40023347,
year = {2025},
author = {Klahan, B and O'Reilly, NJ and Sigurdsson, HH and Chauhan, A and Mering, S and Fitzhenry, L},
title = {Delivery of Fenofibrate to Ocular Tissues using 2-Hydroxypropyl-β-cyclodextrin-Based Micelles.},
journal = {International journal of pharmaceutics},
volume = {673},
number = {},
pages = {125417},
doi = {10.1016/j.ijpharm.2025.125417},
pmid = {40023347},
issn = {1873-3476},
mesh = {Micelles ; *2-Hydroxypropyl-beta-cyclodextrin/chemistry/administration &amp; dosage ; *Fenofibrate/administration &amp; dosage/chemistry/pharmacokinetics ; Animals ; Poloxamer/chemistry ; Solubility ; Polyethylene Glycols/chemistry ; Polyvinyls/chemistry ; Drug Delivery Systems/methods ; *Drug Carriers/chemistry ; Particle Size ; Administration, Ophthalmic ; *Eye/metabolism ; Drug Liberation ; *Hypolipidemic Agents/administration &amp; dosage/chemistry ; },
abstract = {Age-related macular degeneration and diabetic retinopathy are the main diseases that cause vision impairment. The standard treatment for this condition is the intravitreal injection of anti-vascular endothelial growth factor agents, which cause several side effects to the eye after injection. Topical administration would be a more effective method, but the ocular layers act as barriers to drug diffusion. In this research, we presented the preparation and characterization of poly(pseudo)rotaxanes (PPRs) containing 2-hydroxypropyl-β-cyclodextrin (2-HPβCD), Pluronic® F127 (PF127) and Soluplus® to enhance the solubility of fenofibrate (FEB), a poorly water-soluble drug, for potential application in ocular drug delivery. The FEB-loaded micelles and PPRs were investigated using DLS, [1]H NMR and XRD techniques, which demonstrated that FEB could be encapsulated into both micelles and PPRs with small particle sizes (7-67 nm). The inclusion complex between FEB and 2-HPβCD was observed, as evidenced by a high stability constant (K1:1) and the shift in proton positions ([1]H NMR) within the hydrophobic cavity of 2-HPβCD in the FEB-loaded PPR formulations. Moreover, [1]H NMR demonstrated structural modifications involving the PF127/ Soluplus® copolymers and proton shifts at the exterior wall of 2-HPβCD in the FEB-loaded PPR formulations, supporting the interactions between the copolymers and 2-HPβCD. The XRD pattern of free FEB compound, indicating its crystalline structure, whereas the drug-loaded PPRs (PF127/Soluplus®/2-HPβCD) showed an amorphous phase with a single broadband without a sharp diffraction peak, suggesting the transformation of the FEB drug from the crystalline to the amorphous state. Subsequently, the solubility enhancement of FEB in the prepared formulations was evaluated and found that the addition of 2-HPβCD to the mixed PF127/Soluplus® micelles had a 910-fold increase in FEB solubility compared to the intrinsic solubility of the FEB (0.34 ± 0.0011 μg/mL), indicating a synergistic effect of 2-HPβCD in drug solubility enhancement. Ex vivo permeation across porcine eyes revealed that FEB-loaded PPRs helped FEB to cross the scleral tissue with FEB permeation levels varying from 0.27 to 4.25 μg/cm[2]. Mathematical modelling based on Fick's law was employed to explain the transportation of FEB-loaded micelles or PPRs across the scleral tissue and to calculate effective diffusivity (Deff). Thus, this study highlights the potential application of PPRs as an effective drug delivery system for eye disease treatments and the importance of mathematical modelling in understanding drug permeation mechanisms.},
}
@article {pmid40022123,
year = {2025},
author = {Zhang, Q and Lu, B and He, L and Fang, K and Zhu, X and Chen, T and Zhu, Y and Liu, Y and Zhang, P},
title = {Targeting macrophage to myofibroblast transition by circ_0001103 for subretinal fibrosis treatment.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {251},
pmid = {40022123},
issn = {1479-5876},
support = {grant No. gxgwfx2019034//Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province/ ; grant No. 81700867//National Natural Science Foundation of China/ ; 81901519//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Fibrosis ; *RNA, Circular/metabolism/genetics ; *Macrophages/pathology/metabolism ; *Myofibroblasts/pathology/metabolism ; Mice, Inbred C57BL ; Choroidal Neovascularization/pathology/genetics ; MicroRNAs/metabolism/genetics ; *Retina/pathology ; Mice ; },
abstract = {PURPOSE: Subretinal fibrosis is an important cause of visual loss in age-related macular degeneration, but its mechanism remains unclear. This study aims to investigate the role of macrophage-to-myofibroblast transition (MMT) in the formation of subretinal fibrosis and assess whether circ_0001103 can regulate the formation of subretinal fibrosis by regulating MMT.<br><br>METHODS: Subretinal fibrosis was induced in C57BL/6J mice by laser induction. The expression profiles of circRNAs in a choroidal neovascularization (CNV) and subretinal fibrosis mice model were accessed via microarray analysis. MMT was induced by TGF-&#x3b2;1 (2.5&#xa0;ng/ml, 48&#xa0;h). Immunohistochemistry was used to assess macrophages (F4/80), MMT (&#x3b1;-SMA) and fibrovascular lesions (collagenI and Isolectin B4) in vivo. The interaction between circ_0001103, miR-7240-5p, and SLC9A was assessed using a dual-luciferase reporter assay, FISH, RNA immunoprecipitation assay, qRT-PCR and western blot. Finally, immunofluorescence, paraffin section and choroidal flatmounts were used to observe the changes of MMT, subretinal fibrosis and CNV after the intervention of circ_0001103 by intravitreal injection on day 7 after laser induction in mice.<br><br>RESULTS: The results revealed that 58 circRNAs were significantly altered in the RPE-choroid-sclera complexes of CNV mice (p&#x2009;<&#x2009;0.05, fold change&#x2009;>&#x2009;2.0). Additionally, circ_0001103 increased in MMT and subretinal fibrosis mice. Circ_0001103 can sponge miR-7240-5p targeting SLC9A to modulate MMT in vitro. Inhibition of circ_0001103 can suppress MMT, subretinal fibrosis and CNV leakage.<br><br>CONCLUSION: circ_0001103 sponge adsorption miR-7240-5p regulates SLC9A1-mediated MMT and subretinal fibrosis. Inhibition of circ_0001103 can suppress subretinal fibrosis and CNV leakage by inhibiting MMT.},
}
@article {pmid40021512,
year = {2025},
author = {Zhang, T and Liu, M},
title = {Cytokines in age-related eye diseases: pathogenesis and potential targets for innovative therapies.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {398},
number = {8},
pages = {9371-9386},
pmid = {40021512},
issn = {1432-1912},
mesh = {Humans ; *Cytokines/metabolism/immunology ; Animals ; *Aging/immunology ; *Eye Diseases/immunology/drug therapy/metabolism ; Macular Degeneration/immunology/drug therapy ; Dry Eye Syndromes/immunology/drug therapy ; },
abstract = {Age-related eye diseases (AREDs), such as dry eye disease (DED), age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), are significant worldwide health concerns due to their rising prevalence and debilitating effects. Despite substantial research on the pathobiology of AREDs, the impact of immune-related alterations caused by aging is still not well understood. Tissue-resident cells and invading immune cells in the eye control innate responses in the event of damage or infection. However, as cells age, they gradually lose their ability to perform their protective duties and develop abnormal characteristics. Therefore, the disrupted regulation of immune responses in the eyes of older individuals enhances their vulnerability to and the intensity of eye disorders. Cytokines, immune system components, have a role in developing AREDs by contributing to inflammation. This paper examines the deficiencies in the pathogenic and therapeutic aspects of pro-inflammatory cytokines in AREDs that require further investigation in future studies.},
}
@article {pmid40020980,
year = {2025},
author = {Simunovic, MP and Prime, ZJ and Chow, RC and Shao, EH and Madanat, Z and Osaadon, P and Yeo, TH and Oo, KT and Too, LK},
title = {The 1-Step Versus 2-Step Subretinal Injection Trial (1,2-SIT)-A Randomized Controlled Trial to Compare Drug Reflux Following Subretinal Injection.},
journal = {American journal of ophthalmology},
volume = {274},
number = {},
pages = {149-162},
doi = {10.1016/j.ajo.2025.02.018},
pmid = {40020980},
issn = {1879-1891},
mesh = {Humans ; Male ; Female ; Aged ; Visual Acuity/physiology ; *Tissue Plasminogen Activator/administration &amp; dosage/pharmacokinetics ; Single-Blind Method ; *Macular Degeneration/complications/drug therapy/metabolism ; Vitrectomy ; *Subretinal Fluid/metabolism ; *Retinal Hemorrhage/drug therapy/etiology/metabolism ; Fluorophotometry ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors/administration &amp; dosage ; *Fibrinolytic Agents/administration &amp; dosage/pharmacokinetics ; Aged, 80 and over ; Fluorescein/administration &amp; dosage ; Intravitreal Injections ; Fluorescein Angiography ; Middle Aged ; Injections, Intraocular ; Bevacizumab ; },
abstract = {PURPOSE: To estimate in humans, in vivo, drug retention in the subretinal space following either 1- or 2-step subretinal injection (SRI).<br><br>DESIGN: A single-masked, randomized, controlled trial.<br><br>METHODS: Patients presenting with submacular hemorrhage secondary to age-related macular degeneration were randomly allocated to receive subretinal tissue plasminogen activator (50 &#xb5;g in 0.1 mL) with sodium fluorescein (10 &#xb5;g in 0.1 mL) as an optical label either as a 1-step (n = 6) procedure, in which the drug defines the subretinal space, or as a 2-step (n = 6) procedure, in which balanced salt solution is first used to define the subretinal space, following pars plana vitrectomy. All patients underwent air-for-fluid exchange at the completion of surgery with subsequent 20% sulfahexafluoride gas and bevacizumab injection. Reflux of subretinally injected drug was calculated by performing fluorophotometry on the fluid collected at the end of air-for-fluid exchange. Patients received intravitreal anti-VEGF at 4-weekly intervals to the final follow-up at 12 weeks. The primary outcome measure was the proportion of drug reflux. Secondary outcomes included duration of surgery, change in visual acuity (VA), final VA, final foveal thickness, and change in foveal thickness. To determine our fluorophotometric technique's applicability to gene and cell therapy, real-time quantitative polymerase chain reaction was employed to determine adeno-associated viral (AAV) yields following exposure to 0.1 mg/mL sodium fluorescein and its effects on retinal progenitor cells (RPCs) was assessed using a cell viability assay.<br><br>RESULTS: Mean reflux was 4.8% &#xb1; 3.1% (mean &#xb1; SEM, range 0.4%-19.5%) for 1-step SRI and 3.9% &#xb1; 0.9% (range 1.7%-5.3%) for 2-step SRI (no significant difference in means; P = .0155 for the difference in variance). There was no significant difference in the duration of surgery (26.8 &#xb1; 1.2 minutes vs 30 &#xb1; 2.7 minutes), final VA (1.1 &#xb1; 0.26 [Snellen 20/252] vs 1.1 &#xb1; 0.32 [Snellen 20/252] logMAR), change in BCVA (-0.45 &#xb1; 0.27 vs -0.27 &#xb1; 0.23 logMAR) or foveal thickness (139.2 &#xb1; 33.2 &#xb5;m vs 129.8 &#xb1; 21.1 &#xb5;m). Quantitative polymerase chain reaction confirmed that AAV titers are not affected by 0.1 mg/mL sodium fluorescein in vitro, and viability assays suggest that it does not adversely affect RPC viability.<br><br>CONCLUSIONS: This study demonstrates that drug loss following SRI ranged from 0.4% to 19.8% (mean 4.3%). There is no significant difference between 1-step and 2-step SRI in the mean proportion of drug reflux, duration of surgery, change in neural retinal thickness, or change in BCVA. However, there is a significantly greater variability in reflux for 1-step injection compared to 2-step injection. AAV yields are not affected by 0.1 mg/mL sodium fluorescein, nor is RPC viability. These data suggest that sodium fluorescein may be an appropriate means of tracking subretinal AAV gene therapy and retinal cell therapy quantitatively and that the 2-step SRI approach is preferable to 1-step SRI to ensure consistency in drug delivery.},
}
@article {pmid40020897,
year = {2025},
author = {Liu, C and Xu, F and Wei, R and Cheng, Y and Wang, Y and Shi, Y and Yang, K and Peng, W and Jian, W and Wu, H and Li, M},
title = {Metabolomics unveils the role of pipecolic acid in regulating monocytes/macrophages-endothelial cells crosstalk to modulate choroidal neovascularization.},
journal = {Experimental eye research},
volume = {254},
number = {},
pages = {110315},
doi = {10.1016/j.exer.2025.110315},
pmid = {40020897},
issn = {1096-0007},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; *Metabolomics/methods ; *Monocytes/metabolism/drug effects ; *Pipecolic Acids/pharmacology ; Mice ; *Macrophages/metabolism/drug effects ; Disease Models, Animal ; Mice, Inbred C57BL ; Chromatography, Liquid ; Gas Chromatography-Mass Spectrometry ; Humans ; *Endothelial Cells/metabolism/drug effects ; },
abstract = {Choroidal neovascularization (CNV) is a leading cause of vision loss in ocular diseases, including age-related macular degeneration (AMD). Despite extensive research, the underlying mechanisms of CNV remain incompletely understood, with a predominant focus on endothelial dysfunction. CNV, however, is a multi-cellular, multi-stage process involving complex interactions between endothelial cells, monocytes/macrophages, and other immune cells. In this study, we employed a dual-platform metabolomics approach combining liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to identify key metabolic alterations associated with CNV. Our results revealed significant changes in metabolic pathways during CNV progression. Using a myeloid lineage tracing mouse model, we further explored how Pipecolic acid regulates interactions between monocytes/macrophages and endothelial cells, key players in CNV development. We found that Pipecolic acid modulates monocyte/macrophage-endothelial cell crosstalk, inhibiting pathological angiogenesis. These results provide valuable insights into the molecular mechanisms driving CNV and highlight potential therapeutic targets for treating ocular neovascular diseases.},
}
@article {pmid40020685,
year = {2025},
author = {Lv, YX and Li, QY and Duan, P and Zhang, MF and Liu, B and Li, SY and Zhao, TT and Wang, H and Liu, Y and Yin, ZQ},
title = {Safe CNV removal is crucial for successful hESC-RPE transplantation in wet age-related macular degeneration.},
journal = {Stem cell reports},
volume = {20},
number = {3},
pages = {102424},
pmid = {40020685},
issn = {2213-6711},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Choroidal Neovascularization/therapy/pathology ; *Human Embryonic Stem Cells/cytology/transplantation ; *Retinal Pigment Epithelium/cytology/transplantation ; *Stem Cell Transplantation ; *Wet Macular Degeneration/therapy/pathology ; },
abstract = {Subretinal transplantation of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells has demonstrated therapeutic potential in macular degeneration. However, its efficiency is limited in wet age-related macular degeneration (wet AMD) due to choroidal neovascularization (CNV). To investigate the feasibility of hESC-RPE cell transplantation, we employed a surgical approach to induce retinal detachment, which allowed the removal of CNV lesions. After retinal reattachment, hESC-RPE cells were transplanted into the subretinal space. Ten patients were enrolled and divided into 2 groups. No retinal edema or CNV recurrence was observed in group 1 (7 patients without bleeding). Group 2 (3 patients with bleeding) had persistent fundus inflammation, and one patient experienced CNV recurrence. All patients were managed effectively without vision loss. These findings suggest that subretinal transplantation of hESC-RPE cells after CNV removal is safe and well tolerated; however, damage caused during CNV removal may trigger persistent inflammation and CNV recurrence. This study was registered at ClinicalTrials.gov (NCT02749734).},
}
@article {pmid40019526,
year = {2025},
author = {Shetty, R and Jose, J and Maliyakkal, N and D S, S and Johnson, RP and Bandiwadekar, A and Gopan, G and Ugare, SR and Preman, NK},
title = {Micelle nanogel-based drug delivery system for lutein in ocular administration.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {398},
number = {8},
pages = {10611-10623},
pmid = {40019526},
issn = {1432-1912},
support = {RGP2/473/45//King Khalid University/ ; },
mesh = {*Lutein/administration &amp; dosage/chemistry/pharmacokinetics ; Animals ; Micelles ; Administration, Ophthalmic ; *Drug Delivery Systems ; Nanogels ; Chorioallantoic Membrane/metabolism/drug effects ; Cell Line ; Particle Size ; *Antioxidants/administration &amp; dosage/chemistry ; Drug Liberation ; Humans ; Chickens ; Cornea/metabolism/drug effects ; Drug Carriers ; },
abstract = {Recent studies have demonstrated that antioxidants like lutein considerably lower the prevalence of age-related macular degeneration (AMD), which has been connected to blindness in numerous older adults. By halting oxidation, antioxidants reduce the damage that free radicals do. However, the short residence time, low stability, and poor solubility of lutein limit their ocular bioavailability following topical application. This study aimed to develop and characterize a micelle nanogel formulation for the ocular delivery of lutein. The micelle nanogel delivery system suggests a novel therapeutic strategy for administering ocular drugs due to its longer retention on the ocular surface, improved corneal permeability, and lowering the need for frequent administration. We developed a nanosized lutein micelle and incorporated it into a gel base to increase the solubility and ocular permeability. The micelle nanoformulation underwent evaluations like mean particle size, entrapment efficiency (EE), zeta potential, in vitro release investigations, ex vivo permeation tests, cell line studies, and Hen's egg test chorioallantoic membrane (HET-CAM). This nanoformulation exhibited favorable particle size (205.2 ± 15.36 nm), PDI (0.3 ± 0.20), and zeta potential (- 14.2 to + 11.3 mV) with 84.5 ± 1.75% entrapment efficiency. Fourier transform infrared spectroscopy confirmed compatibility, while TEM showed nanoscale spherical structures. F4 demonstrated effective corneal penetration, enhanced fibroblast viability, antioxidant activity (IC50: 55.11 µg/mL), and mild ocular irritancy and better wound healing properties. Based on the results, the formulations were proven safe and efficient for drug delivery to the eyes.},
}
@article {pmid40018174,
year = {2024},
author = {Rogers, JT and Black, J and Harwood, M and Wilkinson, B and Kandel, H and Ramke, J},
title = {Vision impairment and differential access to eye health services in Aotearoa New Zealand: a scoping review.},
journal = {BMJ public health},
volume = {2},
number = {1},
pages = {e000313},
pmid = {40018174},
issn = {2753-4294},
abstract = {INTRODUCTION: In Aotearoa New Zealand, Māori and Pacific People experience worse health outcomes compared with other New Zealanders. No population-based eye health survey has been conducted, and eye health services do not generate routine monitoring reports, so the extent of eye health inequality is unknown. This information is required to plan equitable eye health services. In this scoping review, we aimed to summarise the nature and extent of the evidence reporting vision impairment, its main causes and access to eye health services by ethnicity in New Zealand.<br><br>METHODS: This scoping review was reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. An information specialist conducted a search on MEDLINE and Embase databases in October 2022. Included studies reported outcomes among any population group resident in New Zealand or attendees at New Zealand health facilities. Data screening, full-text review and data extraction were performed independently by two authors. We summarised the characteristics of studies and outcomes, and the results were synthesised narratively.<br><br>RESULTS: Our search identified 2711 reports, of which 53 (from 47 studies) were included. We mapped 72 outcomes, many of which were access-related (n=32), published since 2000 (n=28) and largely focused on diabetic retinopathy (n=21) or cataract (n=13) in facility-based settings (n=18). Over two-thirds of reported outcomes were disaggregated by at least two ethnicities. When outcomes were disaggregated by ethnicity, M&#x101;ori and Pacific People were consistently included, and experienced worse access and outcomes compared with other New Zealanders.<br><br>CONCLUSION: The findings of this review highlight the presence of ethnic disparity in access to diabetic retinopathy and cataract services. Closing the evidence gap identified for refractive error, glaucoma and macular degeneration service coverage could be a priority for future research. Furthermore, future research can be strengthened to enable consistent monitoring of eye health service coverage over time.},
}
@article {pmid40016538,
year = {2025},
author = {Bhatia, B and Sim, SY and Chalkiadaki, E and Koutsocheras, G and Nicholson, L and Selvam, S and Sivaprasad, S and Pal, B and Huemer, J and Keane, PA and Hamilton, R and Patel, PJ and , },
title = {The Impact of Disease Activity Criteria on Extending Injection Intervals in Real-World Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {4},
pages = {773-786},
pmid = {40016538},
issn = {2193-8245},
abstract = {INTRODUCTION: In clinical practice, intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection intervals for patients with neovascular age-related macular degeneration (nAMD) are based on disease activity, with active or recurrent disease requiring more frequent injections. Injection interval modification criteria differ from those used in clinical trials, thereby potentially affecting treatment outcomes. This analysis evaluated the potential impact of applying disease activity criteria from recent clinical trials (TENAYA/LUCERNE; HAWK/HARRIER; PULSAR) on the decision to extend injection intervals in real-world patients commenced on faricimab after the loading phase of treatment and at 12 months.<br><br>METHODS: Data were analysed from 105 treatment-na&#xef;ve patients with nAMD who received anti-VEGF injections at Moorfields Eye Hospital. Disease activity criteria from TENAYA/LUCERNE, HAWK/HARRIER and PULSAR clinical trials were applied to determine the hypothetical impact on the decision to modify injection intervals at week&#xa0;12 (fourth injection) and 12-month real-world clinic visits.<br><br>RESULTS: At 12&#xa0;weeks,&#xa0;79% of patients had injection intervals extended in clinical practice compared to 80% when applying hypothetical TENAYA/LUCERNE disease activity criteria; 77% using HAWK/HARRIER and 96% using PULSAR. There was agreement between clinical practice and all clinical trials in 60% of eyes, and no agreement in 13%. At 12&#xa0;months, fewer patients were inactive, with 55% of eyes quiescent in clinical practice, 58% when applying TENAYA/LUCERNE criteria and 67% using HAWK/HARRIER. Application of PULSAR disease activity criteria showed 96% of patients were classed as inactive. 34% of eyes showed agreement in disease activity status between clinical practice and all clinical trials at 12&#xa0;months, with no agreement in 20%.<br><br>CONCLUSIONS: Applying disease activity criteria from clinical trials to clinical practice can have a significant impact on hypothetical anti-VEGF injection intervals. Consideration should be paid to which criteria are used in real-world practice to help achieve treatment burden reductions and optimal treatment outcomes seen in clinical trials.},
}
@article {pmid40015680,
year = {2025},
author = {Jaffe, GJ and Cameron, B and Barteselli, G and Callaway, N and Skalak, C and Choong, J and Gune, S},
title = {Macular Atrophy-Related Observations in Eyes Treated with the Port Delivery System with Ranibizumab in the Archway Trial.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {8},
pages = {767-773},
doi = {10.1016/j.oret.2025.02.017},
pmid = {40015680},
issn = {2468-6530},
mesh = {Humans ; *Ranibizumab/administration &amp; dosage ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Female ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Tomography, Optical Coherence/methods ; *Macula Lutea/pathology ; Follow-Up Studies ; *Visual Acuity ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Drug Delivery Systems ; Fundus Oculi ; Incidence ; Aged, 80 and over ; Dose-Response Relationship, Drug ; Treatment Outcome ; },
abstract = {PURPOSE: To compare the development of macular atrophy (MA) in eyes treated with the Port Delivery System with ranibizumab (PDS) with those treated with monthly intravitreal ranibizumab injections in the Archway trial.<br><br>DESIGN: Preplanned exploratory analysis of a phase III, open-label, randomized trial.<br><br>PARTICIPANTS: Patients with neovascular age-related macular degeneration (nAMD) diagnosed within 9 months of screening, previously treated with and responsive to anti-VEGF therapy.<br><br>METHODS: Eyes were randomized 3:2 to treatment with the PDS 100 mg/ml with fixed 24-week (Q24W) refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab).<br><br>MAIN OUTCOME MEASURES: Prevalence, incidence, and progression of MA.<br><br>RESULTS: The analysis population consisted of 415 eyes (248 and 167 eyes in the PDS Q24W and monthly ranibizumab arms, respectively). At the study baseline, MA was observed in 22.3% (PDS Q24W) and 20.4% (monthly ranibizumab) of eyes. At week 96, the prevalence of MA was 39.1% and 39.2%, whereas the incidence of new MA in eyes without MA at baseline was 20.0% and 22.6% in the PDS Q24W and monthly ranibizumab arms, respectively. In eyes without baseline MA, the mean MA area at week 96 was 0.4 in the PDS Q24W arm and 3.8 mm[2] in the monthly ranibizumab arm with a difference of 3.4 mm[2], (P = 0.054) favoring the PDS. In eyes with baseline MA, the mean change in MA area from baseline to week 96 was +2.2 mm[2] for both the PDS Q24W and monthly ranibizumab arms.<br><br>CONCLUSIONS: In the Archway trial, which compared PDS Q24W with monthly ranibizumab injections for nAMD treatment over 2 years, the prevalence and incidence of MA were similar between arms over the study duration. In eyes without baseline MA, PDS-treated eyes had less MA area by 3.4 mm[2], a potentially clinically meaningful (although not statistically significant) difference. The results of this prespecified exploratory analysis suggest that PDS treatment is not associated with a higher incidence or progression of MA when compared with monthly injections of ranibizumab. In eyes without baseline MA, the progression of the atrophy area was 4 times less in PDS-treated eyes. Additional studies could further elucidate this observation.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid40015591,
year = {2025},
author = {Janmohamed, IK and Salam, MAU and Jamall, O and Elgharably, M and Ghoz, N and Amarnath, A and Theodoraki, K and Almeida, G},
title = {Faricimab-Associated Intraocular Inflammation With Features of Herpes Simplex Virus.},
journal = {American journal of ophthalmology},
volume = {273},
number = {},
pages = {212-220},
doi = {10.1016/j.ajo.2025.02.033},
pmid = {40015591},
issn = {1879-1891},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; Intravitreal Injections ; Visual Acuity ; Angiogenesis Inhibitors/adverse effects ; Tomography, Optical Coherence ; *Simplexvirus ; Fluorescein Angiography ; Middle Aged ; *Herpes Simplex/virology/diagnosis/drug therapy ; *Eye Infections, Viral/diagnosis/virology/drug therapy ; Aged, 80 and over ; Macular Edema/drug therapy ; Wet Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Endophthalmitis/chemically induced/diagnosis/virology/drug therapy ; Diabetic Retinopathy/drug therapy ; Antibodies, Bispecific ; },
abstract = {OBJECTIVE: Faricimab-associated intraocular inflammation (IOI) is an emerging concern. We aimed to investigate clinical features, management, and outcomes of severe IOI following faricimab therapy, with particular attention to cases displaying features consistent with herpes simplex virus (HSV) involvement.<br><br>DESIGN: Single-center retrospective interventional case series.<br><br>SUBJECTS: Five patients (5 eyes) who developed severe IOI following intravitreal faricimab injection for neovascular age-related macular degeneration (nAMD, n = 4) or diabetic macular edema (DME, n = 1) between June 2023 and October 2024. The nAMD patients had received a mean of 17.75 &#xb1; 9.18 prior anti-VEGF injections (range 6-26 injections). The DME patient had previously received 7 aflibercept injections and 2 dexamethasone implants. Prior to faricimab, 3 patients were being treated with aflibercept and 2 with ranibizumab biosimilar.<br><br>METHODS: Medical records were reviewed for clinical features, treatment approaches, and outcomes. Cases were identified through systematic review of follow-up appointments and urgent care presentations. When clinically indicated, additional investigations including optical coherence tomography and fluorescein angiography were performed.<br><br>MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber (AC) inflammation, presence of keratic precipitates (KPs), vitreous cells, signs of viral reactivation, and treatment response.<br><br>RESULTS: The median number of faricimab injections before inflammation was 5 (range 3-13). Mean interval between injection and symptom onset was 16.8 days (range 1-35). All patients presented with AC inflammation and elevated IOP (mean 32.8 &#xb1; 4.15 mmHg, range 28-38 mmHg). All patients demonstrated features consistent with HSV keratouveitis, including dendritic ulcers, reduced corneal sensation, and granulomatous KPs. Treatment included topical or systemic steroids in all cases, with 4 patients (80%) receiving concurrent antiviral therapy. Median time to inflammation resolution was 15.5 days. Four patients (80%) did not recover baseline vision.<br><br>CONCLUSIONS: This case series identifies a previously unreported association between faricimab-associated IOI and features of viral reactivation. The temporal relationship including onset patterns suggestive of delayed hypersensitivity, alongside consistent HSV features and favourable antiviral response, suggests a possible mechanism linked to VEGF-A and Ang-2 mediated alterations in ocular immune surveillance. While further investigation is needed to establish causality, clinicians should consider viral mechanisms when evaluating and treating these cases.},
}
@article {pmid40015462,
year = {2025},
author = {Tang, Y and Cheng, C and Ding, R and Qian, J and Liu, M and Guo, Y and Li, Q},
title = {MSC exosomes and MSC exosomes loaded with LncRNA H19 as nanotherapeutics regulate the neurogenetic potential of Müller Glial Cells in dry age-related macular degeneration.},
journal = {Free radical biology &amp; medicine},
volume = {231},
number = {},
pages = {178-192},
doi = {10.1016/j.freeradbiomed.2025.02.039},
pmid = {40015462},
issn = {1873-4596},
mesh = {*Exosomes/metabolism/transplantation/genetics ; *RNA, Long Noncoding/genetics/metabolism ; Animals ; Mice ; *Mesenchymal Stem Cells/metabolism ; *Ependymoglial Cells/metabolism/pathology ; Wnt Signaling Pathway ; Oxidative Stress ; *Macular Degeneration/therapy/pathology/genetics/metabolism ; Humans ; Transforming Growth Factor beta1/genetics/metabolism ; Mice, Inbred C57BL ; Male ; Disease Models, Animal ; Iodates/toxicity ; Gliosis/pathology/genetics ; },
abstract = {In retinal degeneration diseases such as dry age-related macular degeneration (AMD), Müller Glial Cells (MGCs) in mammals undergo a process of reactive gliosis leading to the progression of dry AMD. Here, It is demonstrated that exosomes derived from mesenchymal stem cells (MSC exosomes) and MSC exosomes loaded with LncRNA H19, acting as nanotherapeutics, can be regulated by MGCs in dry AMD. In the in vivo study, MSC exosomes were administered via intravitreal injection. MSC exosomes effectively redirected MGCs from gliosis to dedifferentiation and alleviated MGCs-to-epithelial transition by inhibiting oxidative stress in mice with dry AMD induced by NaIO3. In the in vitro study, MSC exosomes promoted MGCs dedifferentiation by activating Wnt/β-catenin signaling pathway and prevented oxidative stress-induced MGCs gliosis and MGCs-to-epithelial transition by inhibiting TGFβ1 signaling pathway. MSC exosomes loaded with LncRNA H19 enhanced the activation of Wnt/β-catenin signaling pathway and the inhibition of the TGFβ1 signaling pathway compared with MSC exosomes. These results suggest that MSC exosomes regulate the neurogenetic potential of MGCs by redirecting MGCs from gliosis to dedifferentiation and alleviating the transformation of MGCs to epithelial cells through regulating oxidative stress. Regulating LncRNA H19 in MGCs to promote mammalian retinal regeneration in dry AMD was suggested for the first time.},
}
@article {pmid40014591,
year = {2025},
author = {Matsumoto, R and Kakinoki, M and Sawada, O and Obata, S and Saishin, Y and Ohji, M},
title = {Incidence of macular hole in patients undergoing pars plana vitrectomy for submacular hemorrhage.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0319266},
pmid = {40014591},
issn = {1932-6203},
mesh = {Humans ; *Vitrectomy/adverse effects ; *Retinal Perforations/epidemiology/etiology/surgery ; Male ; Female ; Aged ; Incidence ; Retrospective Studies ; *Retinal Hemorrhage/surgery ; Middle Aged ; Aged, 80 and over ; Macular Degeneration/complications/surgery ; Retinal Arterial Macroaneurysm/complications/surgery ; },
abstract = {PURPOSE: To investigate the incidence of macular hole (MH) during pars plana vitrectomy (PPV) for submacular hemorrhage (SMH) due to either retinal arterial macroaneurysm (RAM) rupture or age-related macular degeneration (AMD).<br><br>METHODS: We retrospectively evaluated 47 eyes of 47 patients with SMH due to RAM rupture or AMD who underwent PPV. The presence or development of MHs was confirmed intraoperatively by the surgeon. We compared the incidence of MH between the RAM and AMD groups.<br><br>RESULTS: In the RAM group, a MH was found in five of 28 (17.9%) eyes, and a MH was developed in three eyes by the surgical procedure. In the&#xa0;AMD group, there was no MH. All MHs were identified intraoperatively and closed by the same surgical procedure. In the RAM group, subretinal tissue plasminogen activator (t-PA) injection was performed in 12 eyes. Of the 12 eyes, two developed an MH before t-PA subretinal injection. Of the remaining 10 eyes, four (40%) developed an MH intraoperatively or postoperatively.<br><br>CONCLUSION: MHs are complications of PPV for SMH that occur more frequently in patients with SMH due to RAM rupture than in patients with SMH due to AMD.},
}
@article {pmid40013669,
year = {2025},
author = {Mhmud, H and Tigchelaar-Besling, OAM and Vermeulen, JP and Verbraak, FD and Barthelmes, D and Gillies, M and Ponsioen, TL and Klaver, CCW},
title = {[Bevacizumab in age-related macular degeneration: more injections, better vision, at lower costs].},
journal = {Nederlands tijdschrift voor geneeskunde},
volume = {169},
number = {},
pages = {},
pmid = {40013669},
issn = {1876-8784},
mesh = {Humans ; *Bevacizumab/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use/economics/administration &amp; dosage ; *Visual Acuity/drug effects ; Prospective Studies ; *Macular Degeneration/drug therapy/economics ; Male ; Female ; Aged ; Treatment Outcome ; Ranibizumab/therapeutic use/economics ; Netherlands ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; },
abstract = {OBJECTIVE: To study the long-term outcomes of anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) in the Netherlands, where off-label bevacizumab is used as the first choice, compared to countries that typically use ranibizumab or aflibercept.<br><br>DESIGN: Prospective real-world observational study.<br><br>METHODS: A total of 1,617 Dutch eyes were compared with 8,667 eyes from a reference group derived from 13 socio-economically comparable countries. The primary outcome was the mean visual acuity (VA) measured at annual intervals up to 60 months. Secondary outcomes included injection frequency and the rate of switching to an alternative injection type.<br><br>RESULTS: Dutch eyes exhibited higher VA, received two additional injections annually and switched to alternative treatments more frequently (65.2% vs. 50.1%) and sooner (14.6 months vs. 17.9 months).<br><br>CONCLUSION: Dutch patients achieved higher VA after 60 months compared to the reference group. This higher VA was associated with a greater number of injections and a tendency to switch to a more expensive registered anti-VEGF injection type.},
}
@article {pmid40012991,
year = {2024},
author = {Kalaw, FGP and Chen, JS and Baxter, SL},
title = {Variations in Using Diagnosis Codes for Defining Age-Related Macular Degeneration Cohorts.},
journal = {Informatics (MDPI)},
volume = {11},
number = {2},
pages = {},
pmid = {40012991},
issn = {2227-9709},
support = {DP5 OD029610/OD/NIH HHS/United States ; P30 EY022589/EY/NEI NIH HHS/United States ; OT2 OD032644/OD/NIH HHS/United States ; T35 EY033704/EY/NEI NIH HHS/United States ; R01 MD014850/MD/NIMHD NIH HHS/United States ; R01 EY034146/EY/NEI NIH HHS/United States ; },
abstract = {Data harmonization is vital for secondary electronic health record data analysis, especially when combining data from multiple sources. Currently, there is a gap in knowledge as to how studies identify cohorts of patients with age-related macular degeneration (AMD), a leading cause of blindness. We hypothesize that there is variation in using medical condition codes to define cohorts of AMD patients that can lead to either the under- or overrepresentation of such cohorts. This study identified articles studying AMD using the International Classification of Diseases (ICD-9, ICD-9-CM, ICD-10, and ICD-10-CM). The data elements reviewed included the year of publication; dataset origin (Veterans Affairs, registry, national or commercial claims database, and institutional EHR); total number of subjects; and ICD codes used. A total of thirty-seven articles were reviewed. Six (16%) articles used cohort definitions from two ICD terminologies. The Medicare database was the most used dataset (14, 38%), and there was a noted increase in the use of other datasets in the last few years. We identified substantial variation in the use of ICD codes for AMD. For the studies that used ICD-10 terminologies, 7 (out of 9, 78%) defined the AMD codes correctly, whereas, for the studies that used ICD-9 and 9-CM terminologies, only 2 (out of 30, 7%) defined and utilized the appropriate AMD codes (p = 0.0001). Of the 43 cohort definitions used from 37 articles, 31 (72%) had missing or incomplete AMD codes used, and only 9 (21%) used the exact codes. Additionally, 13 articles (35%) captured ICD codes that were not within the scope of AMD diagnosis. Efforts to standardize data are needed to provide a reproducible research output.},
}
@article {pmid40012232,
year = {2025},
author = {Stradiotto, E and Feo, A and Ottonelli, G and Ferraro, V and Del Turco, C and Panico, C and Romano, MR and La Spina, C},
title = {Prechoroidal cleft changes after intravitreal injections of Faricimab in treatment-naïve and nonresponders-to-aflibercept patients: A case series.},
journal = {European journal of ophthalmology},
volume = {35},
number = {4},
pages = {NP16-NP20},
doi = {10.1177/11206721251322541},
pmid = {40012232},
issn = {1724-6016},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Choroid/pathology ; Fluorescein Angiography ; Fundus Oculi ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; Antibodies, Bispecific ; },
abstract = {PurposeTo describe the clinical and optical coherence tomography (OCT) changes of prechoroidal cleft in treatment-naïve and non-naïve neovascular age-related macular degeneration (nAMD) treated with Faricimab intravitreal injections.MethodsA case series (4 eyes from 4 patients).ResultsCases 1 and 2 were diagnosed with treatment-naïve nAMD. Case 1 showed minimal prechoroidal cleft persistence after treatment with visual acuity stabilization. Case 2 showed prechoroidal cleft resolution, followed by its recurrence with neovascular reactivation. Cases 3 and 4 had a history of nAMD unresponsive to Aflibercept therapy. In Case 3, prechoroidal cleft reappearance occurred simultaneously to neovascular reactivation. In Case 4 prechoroidal cleft resolved rapidly after switching to Faricimab, but this was complicated by the development of a retinal pigment epithelium (RPE) tear.ConclusionIn this report, we highlight the importance of prechoroidal cleft as a negative prognostic OCT biomarker despite the increasingly proved efficacy of Faricimab. Pigment epithelium detachment height may correlate with the size of prechoroidal cleft and macular neovascularization (MNV) activity. Further studies are needed to better elucidate the prognostic significance of prechoroidal cleft after Faricimab therapy.},
}
@article {pmid40011740,
year = {2025},
author = {Cheung, CMG},
title = {Age-related macular degeneration in 2025- opportunities and challenges.},
journal = {Eye (London, England)},
volume = {39},
number = {7},
pages = {1231-1232},
pmid = {40011740},
issn = {1476-5454},
support = {OFLCG23 may-0032//MOH | National Medical Research Council (NMRC)/ ; STaR24Jan-0005//MOH | National Medical Research Council (NMRC)/ ; },
}
@article {pmid40010818,
year = {2025},
author = {Sammons, E and Bowman, L and Stevens, W and Buck, G and Hammami, I and Parish, S and Armitage, J and , },
title = {Effects of aspirin and omega-3 fatty acids on age-related macular degeneration in ASCEND-Eye: a randomised placebo-controlled trial in a population with diabetes.},
journal = {BMJ open},
volume = {15},
number = {2},
pages = {e090605},
pmid = {40010818},
issn = {2044-6055},
mesh = {Humans ; *Aspirin/therapeutic use ; *Macular Degeneration/prevention &amp; control/epidemiology/drug therapy ; *Fatty Acids, Omega-3/therapeutic use ; Female ; Male ; Double-Blind Method ; Aged ; Middle Aged ; United Kingdom ; Adult ; Treatment Outcome ; },
abstract = {PURPOSE: Aspirin and omega-3 fatty acids (FAs) are potential disease modifiers of age-related macular degeneration (AMD), but previous studies have produced inconsistent findings. Randomised evidence for the efficacy and safety of aspirin and omega-3 FAs on AMD is presented in this study.<br><br>DESIGN: ASCEND-Eye is a substudy of eye effects in the 2&#xd7;2 factorial design ASCEND (A Study of Cardiovascular Events iN Diabetes) double-blind, randomised, placebo-controlled trial for the primary prevention of cardiovascular events. Reports of AMD diagnoses were sourced from 6&#x2009;monthly ASCEND follow-up questionnaires and a Visual Function Questionnaire.<br><br>PARTICIPANTS: 15&#x2009;480 UK adults at least 40 years of age with diabetes but no evident cardiovascular disease.<br><br>INTERVENTIONS: 100&#x2009;mg aspirin daily versus placebo and, separately, 1&#x2009;g omega-3 FAs daily versus placebo.<br><br>MAIN OUTCOME MEASURE: The first post-randomisation reports of AMD.<br><br>RESULTS: During 7.4 years of follow-up, 122 (1.6%) participants randomised to aspirin were reported as having AMD, compared with 138 (1.8%) randomised to placebo (rate ratio 0.88; 95%&#x2009;CI 0.69 to 1.12; p=0.31). AMD occurred in 130 (1.7%) participants randomised to omega-3 FAs, compared with 130 (1.7%) randomised to placebo (rate ratio 0.99; 95%&#x2009;CI 0.78 to 1.27; p=0.99).<br><br>CONCLUSION: No clinically-meaningful effects of aspirin or omega-3 FAs on AMD were found. Although the study had very limited statistical power to detect clinically relevant effects, these data overcome some methodological limitations of previous observational studies, providing randomised evidence of both treatments on AMD, which could contribute to future meta-analyses.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN60635500 and NCT00135226.},
}
@article {pmid40009268,
year = {2025},
author = {Hariprasad, SM and Holz, FG and Asche, CV and Issa, A and Mora, O and Keady, S and Rezk, MF and Sarocco, P and Simoens, S},
title = {Clinical and Socioeconomic Burden of Retinal Diseases: Can Biosimilars Add Value? A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {4},
pages = {621-641},
pmid = {40009268},
issn = {2193-8245},
abstract = {Retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, pose a significant global burden on individuals, families, and healthcare systems. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has become the standard treatment for retinal diseases, improving clinical outcomes, while delaying disease progression. Although effective, biologics are associated with high costs, which can lead to underutilisation and, consequently, suboptimal patient treatment outcomes, further contributing to healthcare costs. Additionally, the expansion in the elderly population is predicted to significantly increase costs and burden on healthcare systems due to retinal diseases, requiring effective strategies and the utilisation of emerging technologies that are crucial public health priorities for tackling global vision impairment. Recently, anti-VEGF biosimilars have been approved and are expected to provide a cost-effective alternative, while providing equivalent efficacy and comparable safety, immunogenicity, and pharmacokinetic profiles as the reference product. The entry of biosimilars holds the promise of meeting some of these unmet needs, giving physicians and patients access to sustainable treatments that can provide cost-effective therapy, enabling savings to be reinvested into healthcare facilities. This article aims to review the impact of retinal diseases on clinical, social, and financial aspects of patient care, emphasising the potential value of biosimilars in ophthalmology.},
}
@article {pmid40008720,
year = {2025},
author = {Tekin, K and Atilgan, CU},
title = {Full-thickness macular hole associated with drusenoid pigment epithelial detachment in age-related macular degeneration.},
journal = {Arquivos brasileiros de oftalmologia},
volume = {88},
number = {2},
pages = {e20240292},
doi = {10.5935/0004-2749.2024-0292},
pmid = {40008720},
issn = {1678-2925},
}
@article {pmid40005976,
year = {2025},
author = {Nikolaidou, A and Spyratou, E and Sandali, A and Gianni, T and Platoni, K and Lamprogiannis, L and Efstathopoulos, EP},
title = {Utilization of Nanoparticles for Treating Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {2},
pages = {},
pmid = {40005976},
issn = {1424-8247},
abstract = {Age-related macular degeneration (AMD) is a predominant cause of vision loss, posing significant challenges in its management despite advancements such as anti-vascular endothelial growth factor (anti-VEGF) therapy. Nanomedicine, with its novel properties and capabilities, offers promising potential to transform the treatment paradigm for AMD. This review reports the significant advancements in the use of diverse nanoparticles (NPs) for AMD in vitro, in vivo, and ex vivo, including liposomes, lipid nanoparticles, nanoceria, nanofibers, magnetic nanoparticles, quantum dots, dendrimers, and polymer nanoparticles delivered in forms such as gels, eye drops, intravitreally, or intravenously. Drug delivery was the most common use of NPs for AMD, followed by photodynamic therapy dose enhancement, antioxidant function for nanoceria, biomimetic activity, and immune modulation. Innovative approaches arising included nanotechnology-based photodynamic therapy and light-responsive nanoparticles for controlled drug release, as well as gene therapy transfer. Nanomedicine offers a transformative approach to the treatment and management of AMD, with diverse applications. The integration of nanotechnology in AMD management not only provides innovative solutions to overcome current therapeutic limitations but also shows potential in enhancing outcomes and patient quality of life.},
}
@article {pmid40005377,
year = {2025},
author = {Brinkmann, M and Müller, T and Köster, M and Schweighofer, J and Danckwardt, M and Giannaccare, G and Marolo, P and Borrelli, E and Reibaldi, M and El-Shabrawi, Y and Toro, MD},
title = {Optical Coherence Tomography Angiography Flow Signal in Non-Treatment-Naïve Patients with Neovascular Age-Related Macular Degeneration Treated with Faricimab.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {2},
pages = {},
pmid = {40005377},
issn = {1648-9144},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Retrospective Studies ; Aged, 80 and over ; *Macular Degeneration/drug therapy/physiopathology/diagnostic imaging ; Choroid/blood supply/drug effects ; Angiogenesis Inhibitors/therapeutic use ; Middle Aged ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiography/methods ; Choroidal Neovascularization/drug therapy ; Angiopoietin-2 ; Intravitreal Injections ; Antibodies, Bispecific ; },
abstract = {Background and Objectives: Age-related macular degeneration (AMD) remains a leading cause of legal blindness. Anti-Vascular Endothelial Growth Factor (VEGF) agents are the first-line treatment for neovascular AMD (nAMD). The choroid plays a key role in AMD and is affected by the anti-VEGF treatment. Faricimab, a bispecific antibody additionally targeting angiopoietin 2 (Ang2), was recently approved for nAMD treatment. This study investigates the effect of Faricimab on choroidal flow signal. Materials and Methods: Optical coherence tomography angiography images of 29 nAMD eyes were examined retrospectively. Patients had received treatment with other anti-VEGF agents before Faricimab application. The flow signal in the choroid was measured before, after one and after a series of ≥2 Faricimab injections. Results: The flow signal decreased significantly (p = 0.026) at the choriocapillaris (CC) level after ≥2 injections. The flow signal did not show a significant change in Haller's layer but increased slightly in Sattler's layer (p = 0.034). Conclusions: In conclusion, our results show that the flow signal, especially at the CC level, changed during treatment. Despite the known influence of anti-VEGF treatment on the choroid, auxiliary inhibition of Ang2 might enhance this effect. Due to the retrospective nature, moderate sample size and non-treatment, naïve patients, care must be taken while interpreting our observations. Prospective studies with larger sample sizes and treatment-naïve patients will be needed.},
}
@article {pmid40005295,
year = {2025},
author = {Das, UN},
title = {Lipoxin A4 (LXA4) as a Potential Drug for Diabetic Retinopathy.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {2},
pages = {},
pmid = {40005295},
issn = {1648-9144},
mesh = {*Lipoxins/therapeutic use/pharmacology ; Humans ; *Diabetic Retinopathy/drug therapy ; COVID-19/complications ; Anti-Inflammatory Agents/therapeutic use ; Intravitreal Injections ; },
abstract = {The purpose of this review is to propose that lipoxin A4 (LXA4), derived from arachidonic acid (AA), a potent anti-inflammatory, cytoprotective, and wound healing agent, may be useful to prevent and manage diabetic retinopathy (DR). LXA4 suppresses inappropriate angiogenesis and the production of pro-inflammatory prostaglandin E2 (PGE2), leukotrienes (LTs), 12-HETE (12-hydroxyeicosatetraenoic acid), derived from AA by the action of 12-lioxygenase (12-LOX)) interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), as well as the expression of NF-κB, inducible NO (nitric oxide) synthase (iNOS), cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF)-factors that play a role in DR. Thus, the intravitreal injection of LXA4 may form a new approach to the treatment of DR and other similar conditions such as AMD (age-associated macular degeneration) and SARS-CoV-2-associated hyperinflammatory immune response in the retina. The data for this review are derived from our previous work conducted in individuals with DR and from various publications on LXA4, inflammation, and DR.},
}
@article {pmid40004771,
year = {2025},
author = {Honda, S},
title = {The Past, Present, and Future Perspective of Photodynamic Therapy for Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {4},
pages = {},
pmid = {40004771},
issn = {2077-0383},
abstract = {Photodynamic therapy (PDT) has been approved as a therapeutic modality for the management of neovascular age-related macular degeneration (nAMD). PDT can treat macular neovascularization with minimal effects on normal tissue, reducing lesion size and maintaining patients' visual acuity; consequently, it became the choice of intervention for nAMD around the year 2000. However, the visual outcomes of PDT are inferior to those of anti-vascular endothelial growth factor therapy. Thus, PDT is no longer favored, except for the management of some specific phenotypes of nAMD (e.g., polypoidal choroidal vasculopathy and pachychoroid neovasculopathy) that are good candidates for PDT. Despite these circumstances, PDT remains an effective treatment modality for several retinal and choroidal diseases and should be considered for further use. This review summarizes the past and present positions of PDT in the field of ophthalmology and discusses the future perspectives on PDT.},
}
@article {pmid40003880,
year = {2025},
author = {Lee, H and Zhang, S and Ahn, HR and Kim, T and Kim, J and Lee, H and Jung, SH and Kim, J},
title = {Retinal Protective Effect of Mono-Ethyl Fumarate in Experimental Age-Related Macular Degeneration via Anti-Oxidative and Anti-Apoptotic Alterations.},
journal = {International journal of molecular sciences},
volume = {26},
number = {4},
pages = {},
pmid = {40003880},
issn = {1422-0067},
support = {2E33311//Korea Institute of Science and Technology/ ; },
mesh = {Animals ; Mice ; Cell Line ; *Retina/drug effects ; *Fumarates/pharmacology ; Macular Degeneration/drug therapy ; Oxidation-Reduction ; *Apoptosis/drug effects ; Mice, Inbred C57BL ; Male ; *Retinal Diseases/chemically induced/metabolism/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment in people over the age of 60. Currently, the FDA-approved drugs for AMD have various side effects, and there is a notable lack of drug development for dry AMD. This study aimed to explore the therapeutic effects of mono-ethyl fumarate (MEF) on AMD. MEF effectively protected ARPE-19 cells from cell death induced by a combination of A2E and blue light exposure. In a C57BL/6J mouse model of retinal degeneration caused by sodium iodate, MEF played a role in preserving retinal thickness and maintaining the layered structure of the retina. It was assessed via fundus imaging, optical coherence tomography, and hematoxylin and eosin staining. Treatment with MEF significantly increased the expression of antioxidant proteins such as HO-1, NQO1, and SOD1 in ARPE-19 cells. Additionally, treatment with MEF significantly increased the levels of the antioxidant proteins SOD1 and GPX4 in the mouse retina. Concurrently, it significantly reduced the levels of apoptosis-related factors, such as the Bax/Bcl-2 ratio and Caspase -3 cleavage. These findings suggest that MEF may represent a promising therapeutic candidate for the management of AMD.},
}
@article {pmid40002842,
year = {2025},
author = {Poboży, K and Poboży, T and Domański, P and Derczyński, M and Konarski, W and Domańska-Poboża, J},
title = {Evolution of Light-Sensitive Proteins in Optogenetic Approaches for Vision Restoration: A Comprehensive Review.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
pmid = {40002842},
issn = {2227-9059},
abstract = {Retinal degenerations, such as age-related macular degeneration and retinitis pigmentosa, present significant challenges due to genetic heterogeneity, limited therapeutic options, and the progressive loss of photoreceptors in advanced stages. These challenges are compounded by difficulties in precisely targeting residual retinal neurons and ensuring the sustained efficacy of interventions. Optogenetics offers a novel approach to vision restoration by inducing light sensitivity in residual retinal neurons through gene delivery of light-sensitive opsins. This review traces the evolution of opsins in optogenetic therapies, highlighting advancements from early research on channelrhodopsin-2 (ChR2) to engineered variants addressing key limitations. Red-shifted opsins, including ReaChR and ChrimsonR, reduced phototoxicity by enabling activation under longer wavelengths, while Chronos introduced superior temporal kinetics for dynamic visual tracking. Further innovations, such as Multi-Characteristic Opsin 1 (MCO1), optimized opsin performance under ambient light, bridging the gap to real-world applications. Key milestones include the first partial vision restoration in a human patient using ChrimsonR with light-amplifying goggles and ongoing clinical trials exploring the efficacy of opsin-based therapies for advanced retinal degeneration. While significant progress has been made, challenges remain in achieving sufficient light sensitivity for functional vision under normal ambient lighting conditions in a manner that is both effective and safe, eliminating the need for external light-enhancing devices. As research progresses, optogenetic therapies are positioned to redefine the management of retinal degenerative diseases, offering new hope for millions affected by vision loss.},
}
@article {pmid40002582,
year = {2025},
author = {Davey, PG and Rosen, RB and Park, JJ and Spors, F and Gierhart, DL},
title = {Evaluation of a Portable Handheld Heterochromatic Flicker Photometer in Measuring Macular Pigment Optical Density.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
pmid = {40002582},
issn = {2075-4418},
support = {(WesternU Grant # 25222-1397).//The study was funded with an unrestricted grant to the Western University of Health Sciences to investigate the currently available MPOD devices/ ; },
abstract = {Background/Objectives: Macular pigment optical density (MPOD) is an important clinical biomarker for ocular conditions like macular degeneration, diabetic eye disease, and digital eye strain. Additionally, its measurements can be essential in health assessment for visual function, systemic diseases, and brain health. We aimed to assess the repeatability, agreement, and effects of the learning curve of the new portable handheld heterochromatic flicker photometer, Zx Pro, in measuring MPOD in a wide age range of ocular-healthy adults, compared to the MPOD measurements obtained using the clinically available QuantifEye device. Methods: Seventy-six participants performed one practice attempt and two study-related MPOD measurements with the Zx Pro and the QuantifEye. Results: The Pearson correlation between the study-related MPOD measurements for Zx Pro and QuantifEye devices was 90% and 85%, respectively. Bland and Altman plots show excellent agreement between the device's MPOD data, with 95% limits of an agreement being -0.10 to +0.11 du. The mean difference between the practice attempt and the study-related measurements was not statistically significant for Zx Pro but was significant for QuantifEye (Repeated measures ANOVA p = 0.325 and p = 0.015, respectively). Conclusions: The Zx Pro provides excellent repeatable MPOD measurements, has an insignificant learning curve, and is in good agreement with the predicate device.},
}
@article {pmid40002374,
year = {2025},
author = {Mancuso, C},
title = {The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
pmid = {40002374},
issn = {2076-3921},
abstract = {Heme oxygenase (HO) metabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin-IXα (BV), the latter being reduced into bilirubin-IXα (BR) by the biliverdin reductase-A (BVR). Heme oxygenase exists as two isoforms, HO-1, inducible and involved in the cell stress response, and HO-2, constitutive and committed to the physiologic turnover of heme and in the intracellular oxygen sensing. Many studies have identified genetic variants of the HO/BVR system and suggested their connection in free radical-induced diseases. The most common genetic variants include (GT)n dinucleotide length polymorphisms and single nucleotide polymorphisms. Gain-of-function mutations in the HO-1 and HO-2 genes foster the ventilator response to hypoxia and reduce the risk of coronary heart disease and age-related macular degeneration but increase the risk of neonatal jaundice, sickle cell disease, and Parkinson's disease. Conversely, loss-of-function mutations in the HO-1 gene increase the risk of type 2 diabetes mellitus, chronic obstructive pulmonary disease, and some types of cancers. Regarding BVR, the reported loss-of-function mutations increase the risk of green jaundice. Unfortunately, the physiological role of the HO/BVR system does not allow for the hypothesis gene silencing/induction strategies, but knowledge of these mutations can certainly facilitate a medical approach that enables early diagnoses and tailored treatments.},
}
@article {pmid40002339,
year = {2025},
author = {Parmar, UPS and Surico, PL and Mori, T and Singh, RB and Cutrupi, F and Premkishore, P and Gallo Afflitto, G and Di Zazzo, A and Coassin, M and Romano, F},
title = {Antioxidants in Age-Related Macular Degeneration: Lights and Shadows.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
pmid = {40002339},
issn = {2076-3921},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment worldwide, primarily driven by oxidative stress and inflammation. This review examines the role of antioxidants in mitigating oxidative damage, emphasizing both their therapeutic potential and limitations in AMD management. Key findings underscore the efficacy of specific antioxidants, including vitamins C and E, lutein, zeaxanthin, and Coenzyme Q10, in slowing AMD progression. Landmark studies such as AREDS and AREDS2 have shaped current antioxidant formulations, although challenges persist, including patient variability and long-term safety concerns. Emerging therapies, such as mitochondrial-targeted antioxidants and novel compounds like saffron and resveratrol, offer promising avenues for AMD treatment. Complementary lifestyle interventions, including antioxidant-rich diets and physical activity, further support holistic management approaches. This review highlights the critical role of antioxidants in AMD therapy, advocating for personalized strategies to optimize patient outcomes.},
}
@article {pmid40001676,
year = {2025},
author = {Kumar, R and Ong, J and Waisberg, E and Lee, R and Nguyen, T and Paladugu, P and Rivolta, MC and Gowda, C and Janin, JV and Saintyl, J and Amiri, D and Gosain, A and Jagadeesan, R},
title = {Applications of Machine Learning-Driven Molecular Models for Advancing Ophthalmic Precision Medicine.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {40001676},
issn = {2306-5354},
abstract = {Ophthalmic diseases such as glaucoma, age-related macular degeneration (ARMD), and optic neuritis involve complex molecular and cellular disruptions that challenge current diagnostic and therapeutic approaches. Advanced artificial intelligence (AI) and machine learning (ML) models offer a novel lens to analyze these diseases by integrating diverse datasets, identifying patterns, and enabling precision medicine strategies. Over the past decade, applications of AI in ophthalmology have expanded from imaging-based diagnostics to molecular-level modeling, bridging critical gaps in understanding disease mechanisms. This paper systematically reviews the application of AI-driven methods, including reinforcement learning (RL), graph neural networks (GNNs), Bayesian inference, and generative adversarial networks (GANs), in the context of these ophthalmic conditions. RL models simulate transcription factor dynamics in hypoxic or inflammatory environments, offering insights into disrupted molecular pathways. GNNs map intricate molecular networks within affected tissues, identifying key inflammatory or degenerative drivers. Bayesian inference provides probabilistic models for predicting disease progression and response to therapies, while GANs generate synthetic datasets to explore therapeutic interventions. By contextualizing these AI tools within the broader framework of ophthalmic disease management, this review highlights their potential to transform diagnostic precision and therapeutic outcomes. Ultimately, this work underscores the need for continued interdisciplinary collaboration to harness AI's potential in advancing the field of ophthalmology and improving patient care.},
}
@article {pmid39999827,
year = {2025},
author = {Faes, L and Jung, JJ and Sorenson, J and Freund, KB},
title = {Atypical Autofluorescence Findings in Geographic Atrophy: The Influence of Age-Related Choroidal Atrophy.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001739},
pmid = {39999827},
issn = {1937-1578},
abstract = {PURPOSE: To describe atypical fundus autofluorescence (FAF) patterns in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) with associated age-related choroidal atrophy (ARCA).<br><br>METHODS: Multimodal imaging of two cases using (pseudo-)color fundus photography, optical coherence tomography (OCT), fluorescein and indocyanine green angiography, and FAF employed with blue- and green excitation wavelengths on several devices (Spectralis, Heidelberg and (ultra-)widefield [UWF] FAF [California, Optos and EIDON, iCare]).<br><br>RESULTS: Two female patients, with foveal-involving GA secondary to AMD, were assessed. All eyes demonstrated concurrent features indicative of ARCA on multimodal imaging including a paucity of choroidal vasculature, reduced choroidal pigmentation, macular pigmentary changes, peripapillary atrophy, and subretinal drusenoid deposits. Clinically, progression of GA with coalescence of lobular lesions was observed. Notably, UWF FAF with green-(California) and blue excitation wavelengths (California and EIDON) revealed atypical patterns characterized by isofluorescent FAF signals (indistinguishable from surrounding tissue) or hyperautofluorescent GA lesions. In these cases, blue excitation wavelengths were more effective than green light for delineating GA, owing to increased contrast from hypoautofluorescence related to macular pigment surrounding the lesion.<br><br>CONCLUSION: In patients with GA and concomitant ARCA, atypical FAF patterns on UWF imaging complicate the accurate delineation and monitoring of GA. Atypical FAF patterns appear due to the properties of the confocal apertures and postprocessing features of UWF imaging that allow for the detection of scleral autofluorescence in patients with reduced choroidal vasculature, pigment and thickness. In patients with concomitant ARCA, multimodal imaging plays a crucial role in precisely identifying and tracking GA progression.},
}
@article {pmid39999658,
year = {2025},
author = {Xu, X and Wang, H and Lu, Y and Zhang, H and Tan, T and Xu, F and Lei, J},
title = {Joint segmentation of retinal layers and fluid lesions in optical coherence tomography with cross-dataset learning.},
journal = {Artificial intelligence in medicine},
volume = {162},
number = {},
pages = {103096},
doi = {10.1016/j.artmed.2025.103096},
pmid = {39999658},
issn = {1873-2860},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Retina/diagnostic imaging/pathology ; *Macular Degeneration/diagnostic imaging/pathology ; Neural Networks, Computer ; *Image Processing, Computer-Assisted/methods ; Algorithms ; },
abstract = {BACKGROUND AND OBJECTIVES: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people over 50 years old, which manifests in the retina through various changes of retinal layers and pathological lesions. The accurate segmentation of optical coherence tomography (OCT) image features is crucial for the identification and tracking of AMD. Although the recent developments in deep neural network have brought profound progress in this area, accurately segmenting retinal layers and pathological lesions remains a challenging task because of the interaction between these two tasks.<br><br>METHODS: In this study, we propose a three-branch, hierarchical multi-task framework that enables joint segmentation of seven retinal layers and three types of pathological lesions. A regression guidance module is introduced to provide explicit shape guidance between sub-tasks. We also propose a cross-dataset learning strategy to leverage public datasets with partial labels. The proposed framework was evaluated on a clinical dataset consisting of 140 OCT B-scans with pixel-level annotations of seven retinal layers and three types of lesions. Additionally, we compared its performance with the state-of-the-art methods on two public datasets.<br><br>RESULTS: Comprehensive ablation showed that the proposed hierarchical architecture significantly improved performance for most retinal layers and pathological lesions, achieving the highest mean DSC of 76.88&#xa0;%. The IRF also achieved the best performance with a DSC of 68.15&#xa0;%. Comparative studies demonstrated that the hierarchical multi-task architecture could significantly enhance segmentation accuracy and outperform state-of-the-art methods.<br><br>CONCLUSION: The proposed framework could also be generalized to other medical image segmentation tasks with interdependent relationships.},
}
@article {pmid39999360,
year = {2025},
author = {Wykoff, CC and Jackson, TL and Price, CF and Baldwin, ME and Leitch, IM and Slakter, J},
title = {Sozinibercept Combination Therapy for Neovascular Age-related Macular Degeneration: Phase 2b Study Subgroup Analysis by Lesion Type.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {5},
pages = {287-296},
doi = {10.3928/23258160-20250108-04},
pmid = {39999360},
issn = {2325-8179},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity ; Intravitreal Injections ; Male ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Double-Blind Method ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; Fluorescein Angiography ; Tomography, Optical Coherence ; Drug Therapy, Combination ; Treatment Outcome ; Ranibizumab/administration &amp; dosage ; Aged, 80 and over ; Fundus Oculi ; Middle Aged ; Follow-Up Studies ; },
abstract = {BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the angiographic predictors of response to the anti-vascular endothelial growth factor-C/-D agent, sozinibercept.<br><br>PATIENTS AND METHODS: Prespecified and post hoc subgroup analyses of a phase 2b, randomized, double-masked, sham-controlled trial of 240 participants with treatment-na&#xef;ve neovascular age-related macular degeneration, comparing monthly intravitreal sozinibercept 0.5 mg or 2 mg, plus ranibizumab 0.5 mg, versus monthly ranibizumab monotherapy.<br><br>RESULTS: Visual acuity benefits at week 24 were greatest in participants with occult lesions receiving 2 mg sozinibercept combination therapy (+15.65 [n = 53] letters versus +9.62 [n = 51] with ranibizumab monotherapy; least squares mean difference +6.03; P = 0.0009). A composite analysis of occult and minimally classic lesions excluding retinal angiomatous proliferation (n = 175/240) also favored sozinibercept over control (+16.08 versus +10.34 letters; +5.74; P = 0.0002). Structural outcomes mirrored sozinibercept visual acuity benefits, with less leakage and smaller lesions on multimodal imaging.<br><br>CONCLUSION: Angiographic lesion characteristics were found to predict the response to sozinibercept combination therapy. [Ophthalmic Surg Lasers Imaging Retina 2025;56:287-296.].},
}
@article {pmid39998939,
year = {2025},
author = {Morikawa, H and Yoshida, T and Kashizuka, E and Hayashi, S and Yokoi, T and Tomita, K and Azuma, N and Nishina, S},
title = {CHOROIDAL NEOVASCULARIZATION IN A CHILD WITH DOWN SYNDROME.},
journal = {Retinal cases &amp; brief reports},
volume = {19},
number = {2},
pages = {273-277},
doi = {10.1097/ICB.0000000000001541},
pmid = {39998939},
issn = {1937-1578},
support = {20FC1055//Ministry of Health, Labour and Welfare/ ; 23FC1052//Ministry of Health, Labour and Welfare/ ; 23FC1055//Ministry of Health, Labour and Welfare/ ; },
mesh = {Humans ; *Down Syndrome/complications ; Male ; Child ; *Choroidal Neovascularization/etiology/diagnosis/drug therapy ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; Visual Acuity ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Fundus Oculi ; },
abstract = {PURPOSE: The aim of this study was to report a case of Down syndrome with myopic choroidal neovascularization (CNV) and the treatment outcome.<br><br>METHODS: Case report: Main outcome measures include refractive error, fundus examination, optical coherence tomography, OCT angiography, fluorescein angiography, and anti-vascular endothelial growth factor injections.<br><br>RESULTS: A 12-year-old boy with Down syndrome presented at a regular checkup with decreased visual acuity with macular degeneration in the left eye. The best-corrected visual acuity was 0.6 in the right eye and 0.1 in the left eye, which decreased from 0.3 one year ago. The refractive error (spherical equivalent) was -5.25 diopters (D) in the right eye and -8.00 D in the left eye. Detailed examinations were performed under general anesthesia. The fundus examination showed macular degeneration with retinal pigment epithelium atrophy, pigmentary changes, and fibrous tissue in the left eye. Optical coherence tomography showed CNV at the macula with edema, and OCT angiography showed spreading CNV above the retinal pigment epithelium at the macula in the left eye. Fluorescein angiography showed hyperfluorescence in the early phase and late dye leakage from the CNV. Intravitreal ranibizumab injections were administered twice within 2 months, and he maintained a visual acuity of 0.1 in the left eye.<br><br>CONCLUSION: CNV and associated macular degeneration may occur in Down syndrome with high myopia possibly because of the abnormal choroidal structure. In children with Down syndrome, regular fundus examinations with optical coherence tomography are important for early detection and treatment of CNV.},
}
@article {pmid39998136,
year = {2025},
author = {Wang, L and Liu, S and He, T and Liu, C and Duan, J},
title = {Efficacy of Intravitreal Anti-VEGF Agents in Neovascular Age-Related Macular Degeneration Patients with or without Polypoidal Choroidal Vasculopathy: A Meta-Analysis.},
journal = {British journal of hospital medicine (London, England : 2005)},
volume = {86},
number = {2},
pages = {1-22},
doi = {10.12968/hmed.2024.0673},
pmid = {39998136},
issn = {1750-8460},
mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Choroidal Neovascularization/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Polypoidal Choroidal Vasculopathy ; },
abstract = {Aims/Background The classification of polypoidal choroidal vasculopathy (PCV) as a subtype of neovascular age-related macular degeneration (nAMD) remained an ongoing controversy. This meta-analysis examines the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in nAMD patients with or without PCV. Methods A systematic search was conducted in four databases, including PubMed, EMBASE, MEDLINE, and Cochrane Library, from their inception to 1 July 2023. The outcome measure was the change in best-corrected visual acuity (BCVA) and center retinal thickness (CRT) from the baseline to different follow-up durations. Furthermore, sensitivity analysis was performed when significant heterogeneity was detected. Results This meta-analysis included sixteen studies involving 6679 patients, comprising 5070 non-PCV and 1609 PCV cases. The findings revealed that the improvement in BCVA at 6-month follow-up (mean difference (MD) = 0.05; 95% confidence interval (CI), 0.02 to 0.07; p = 0.0001) and the reduction in CRT at 3-month follow-up duration (MD = 10.29; 95% CI, 0.93 to 19.66; p = 0.03) were significantly greater in the PCV group compared to the non-PCV group. Conclusion This meta-analysis indicates that PCV may exhibit better short-term efficacy in response to anti-VEGF therapy than non-PCV. Systematic Review Registration PROSPERO (CRD42023445591).},
}
@article {pmid39994686,
year = {2025},
author = {Webster, SE and Les, SM and Deleon, N and Heck, DM and Tsuj, NL and Clemente, MJ and Jones, P and Holodick, NE},
title = {Secreted IgM deficiency alters the retinal landscape enhancing neurodegeneration associated with aging.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {22},
number = {1},
pages = {9},
pmid = {39994686},
issn = {1742-4933},
support = {F32 AI174673/AI/NIAID NIH HHS/United States ; R01 AI154539/AI/NIAID NIH HHS/United States ; F32AI174673-01A1//National Institute of Allergy and Infectious Diseases/ ; 1R01AI154539-01//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {BACKGROUND: Maintenance of the retina, part of the central nervous system, and other structures in the eye is critical for vision preservation. Aging increases the prevalence of vision impairment, including glaucoma, macular degeneration, and diabetic retinopathy. The retina is primarily maintained by glial cells; however, recent literature suggests that lymphocytes may play a role in the homeostasis of central nervous system tissues. Natural antibodies are produced by B cells without infection or immunization and maintain tissue homeostasis. Here, we explored the potential role of natural immunoglobulin M (IgM) produced by B lymphocytes in maintaining retinal health during aging in mice.<br><br>RESULTS: Our results indicate that the vitreous humor of both mice and humans contains IgM and IgG, suggesting that these immunoglobulins may play a role in ocular function. Furthermore, we observed that aged mice lacking secreted IgM (&#xb5;s-/-) exhibited pronounced retinal degeneration, accompanied by reactive gliosis, and a proinflammatory cytokine environment. This contrasts with the aged wild-type counterparts, which retain their ability to secrete IgM and maintain a better retinal structure and anti-inflammatory environment. In addition to these findings, the absence of secreted IgM was associated with significant alterations in the retinal pigment epithelium, including disruptions to its morphology and signs of increased stress. This was further observed in changes to the blood-retinal-barrier, which is critical for regulation of retinal homeostasis.<br><br>CONCLUSIONS: These data suggest a previously unrecognized association between a lack of secreted IgM and alterations in the retinal microenvironment, leading to enhanced retinal degeneration during aging. Although the precise mechanism remains unclear, these findings highlight the potential importance of secreted IgM in processes that support retinal health over time. By increasing our understanding of ocular aging, these results show that there is a broader role for the immune system in retinal function and integrity in advanced age, opening new areas for the exploration of immune-related interventions in age-associated retinal conditions.},
}
@article {pmid39994103,
year = {2025},
author = {Wojciechowski, P and Wdowiak, M and Panek, M and Lunk, I and Carrasco, J and Zhang, X and Wu, O and Korobelnik, JF and Lanzetta, P},
title = {Efficacy, Safety, and Injection Frequency with Novel Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration: A Comparison with Existing Anti-VEGF Regimens Using a Bayesian Network Meta-Analysis.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {4},
pages = {733-753},
pmid = {39994103},
issn = {2193-8245},
abstract = {INTRODUCTION: Aflibercept 8 mg administered in extended dosing intervals has shown non-inferior visual gains and comparable safety profile to aflibercept 2 mg in the PULSAR pivotal randomized clinical trial and has the potential to reduce the treatment burden of treating neovascular age-related macular degeneration (nAMD). This study aimed at gathering robust evidence to assess the comparative efficacy, safety, and treatment burden of aflibercept 8 mg against other anti-vascular endothelial growth factor (VEGF) agents as ranibizumab, brolucizumab, faricimab, and bevacizumab in patients with nAMD.<br><br>METHODS: A systematic literature review (SLR) was conducted, targeting clinical trials of anti-VEGF agents in patients with nAMD. The results of the SLR were included in a network meta-analysis (NMA) comparing aflibercept 8 mg to other anti-VEGF treatments in nAMD, considering a 1-year time horizon. Treatment efficacy was assessed based on the change in best-corrected visual acuity (BCVA) from baseline, the proportion of patients gaining or losing 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and changes in anatomical outcomes measured as change in central retinal thickness (CRT) or central subfield thickness (CST). Safety was assessed considering the incidence of ocular and non-ocular adverse events. Treatment burden was defined as the mean number of intravitreal injections over the study period.<br><br>RESULTS: The base-case NMA involving 21 studies did not show significant differences between aflibercept 8 mg and comparators regarding BCVA change from baseline and proportion of patients with a gain or loss of&#x2009;&#x2265;&#x2009;15 letters. On the anatomical endpoints, aflibercept 8 mg was associated with statistically significant improvement in CRT/CST change from baseline compared with ranibizumab in fixed and pro re nata regimens. No significant differences were identified versus the other anti-VEGF. The analysis of the safety outcomes did not identify any significant differences between aflibercept 8 mg and any of the comparators. During the first year of treatment, patients treated with aflibercept 8 mg (following 12- or 16-week injection intervals) received on average 5.9 and 5.1 injections, respectively. For the same period, patients treated with faricimab received from 6.2 to 6.7 injections, patients treated with ranibizumab from 7.62 to 12.14 injections, and patients treated with aflibercept 2 mg up to 7.67 injections.<br><br>CONCLUSION: Aflibercept 8 mg demonstrates a comparable efficacy and safety to currently available anti-VEGF treatments for nAMD, with the potential added benefit of requiring fewer injections. These results suggest that aflibercept 8 mg could be a favourable treatment option for nAMD, achieving sustained disease control while alleviating the burden of injections on patients, caregivers, and healthcare providers.},
}
@article {pmid39993131,
year = {2025},
author = {Babaker, R and Alzimami, L and Al Ameer, A and Almutairi, M and Alam Aldeen, R and Alshatti, H and Al-Johani, N and Al Taisan, A},
title = {Risk factors for age-related macular degeneration: Updated systematic review and meta-analysis.},
journal = {Medicine},
volume = {104},
number = {8},
pages = {e41599},
pmid = {39993131},
issn = {1536-5964},
mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; Risk Factors ; Aged ; Male ; Age Factors ; Female ; Sex Factors ; Hypertension/epidemiology/complications ; Smoking/epidemiology/adverse effects ; Cardiovascular Diseases/epidemiology/complications ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in the elderly population, affecting millions of the people worldwide. AMD has a substantial effect on quality of life in older individuals. Understanding and identifying risk factors are crucial for developing preventive strategies.<br><br>METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search across databases including PubMed, Scopus, and Web of Science up to January 28, 2024. Studies were selected using standardized inclusion and exclusion criteria, and the quality of the studies was assessed via the Newcastle Ottawa Scale. Meta-analysis was conducted using Review Manager software to pool the odds ratio (OR) of each included risk factors at the 95% confidence interval (CI).<br><br>RESULTS: Eighteen of the 2640 identified studies met the inclusion criteria for the meta-analysis. Older age compared to younger age, male gender compared to female gender, smoking, hypertension, cardiovascular diseases, and diabetes were statistically significant predictors for AMD occurrence, with ORs of 1.11 (95% CI = 1.06-1.15, P&#x2005;<&#x2005;.00001), 1.63 (95% CI = 1.13-2.35, P&#x2005;=&#x2005;.009), 1.86 (95% CI = 1.33-2.6, P&#x2005;=&#x2005;.0003), 1.24 (95% CI = 1.09-1.4, P&#x2005;=&#x2005;.0007), 1.44 (95% CI = 1.11-1.87, P&#x2005;=&#x2005;.006), and 1.44 (95% CI = 1.3-1.6, P&#x2005;<&#x2005;.00001), respectively. Other factors, such as body mass index, cerebrovascular diseases, cholesterol, and triglycerides, were not significantly associated with AMD.<br><br>CONCLUSION: This updated meta-analysis highlights the significance of modifiable risk factors for AMD, including smoking, hypertension, cardiovascular diseases, and diabetes. Early identification of AMD accompanied by strategic management of these modifiable risk factors may preserve patients' visual acuity without advancing to advanced stages.},
}
@article {pmid39992662,
year = {2025},
author = {Savastano, MC and Fossataro, C and Carlà, MM and Cestrone, V and Biagini, I and Rizzo, C and Kilian, R and Zweifel, SA and Muth, DR and Faraldi, F and Rizzo, S and Sarraf, D},
title = {OCT Angiography of Type 1 Macular Neovascularization in AMD: A Morphometric Evaluation.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {2},
pages = {23},
pmid = {39992662},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Cross-Sectional Studies ; Male ; Female ; Aged ; *Fluorescein Angiography/methods ; Visual Acuity ; Aged, 80 and over ; Retinal Vessels/diagnostic imaging/pathology ; Middle Aged ; *Macular Degeneration/diagnostic imaging ; *Choroidal Neovascularization/diagnostic imaging ; *Wet Macular Degeneration/diagnostic imaging ; Macula Lutea ; },
abstract = {PURPOSE: To determine biomarkers of macular neovascularization (MNV) in neovascular age-related macular degeneration through the application of an automatic algorithm based optical coherence tomography angiography (OCTA) analysis.<br><br>METHODS: In this retrospective, observational, single-center, cross-sectional study, patients with a diagnosis of age-related macular degeneration complicated by type 1 MNV were included. MNV was detected with OCTA and scans were analyzed with a qualitative and quantitative open-source image processing package. For each analyzed image, we automatically acquired the following data: Total MNV area, vessel area, vessel density (VD), total number of branches, total number of vascular junctions, mean vessel length, mean vessel diameter, fractal dimension (FD),&#xa0;junction density, and vessel tortuosity.<br><br>RESULTS: The following morphological parameters revealed a significant negative correlation with best-corrected visual acuity: MNV area - Spearman &#x3c1; = -0.309 (P = 0.002); vessel area - Spearman &#x3c1; = -0.315 (P = 0.002); total number of vascular junctions - Spearman &#x3c1; = -0.285 (P = 0.005), and VL - Spearman &#x3c1; = -0.304 (P = 0.003). Immature MNV lesions were significantly associated with better vessel area than mature and hypermature lesions.<br><br>CONCLUSIONS: Several automated MNV-associated morphological parameters can correlate with the best-corrected visual acuity. Further studies are warranted to determine if these OCTA biomarkers can be applied to guide anti-vascular endothelial growth factor therapy and predict response to treatment.<br><br>TRANSLATIONAL RELEVANCE: The analysis of MNV biomarkers may have prognostic value in terms of visual function.},
}
@article {pmid39991354,
year = {2025},
author = {Evans, W and Evans, M and Eissa, M},
title = {Efficacy and Safety of High-Dose Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration (nAMD): A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {1},
pages = {e77906},
pmid = {39991354},
issn = {2168-8184},
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide, and so continued research into new treatment options remains a priority. No systematic review has yet analysed the effectiveness and safety of higher-dose aflibercept across the available literature. We aimed to systematically evaluate the efficacy and safety of higher-dose intravitreal aflibercept (>2 mg) on Central Retinal Thickness (CRT) and Best Corrected Visual Acuity (BCVA) in patients with neovascular AMD (nAMD). In order to achieve this, a systematic literature search was conducted in January 2025 using PubMed and Ovid MEDLINE databases. Results were screened, and inclusion criteria were applied. Studies were included if they reported outcome data for intravitreal aflibercept doses above 2 mg for the treatment of nAMD. Of 382 identified articles, eight studies met inclusion criteria, encompassing data from 903 eyes. Analysis of all studies combined revealed a statistically significant improvement at 10 months, with a 33% reduction in CRT and a 29% improvement in BCVA. Subgroup analysis suggested greater effectiveness of 8 mg compared to 3 mg doses, particularly for CRT reduction (36% at 10 months vs. 28% at 12 months). However, small sample sizes and high heterogeneity across studies, including variations in dose, injection intervals, and patient characteristics (e.g., treatment-naïve vs. treatment-resistant), limit the reliability and conclusions of these outcome findings. There was a complication rate of 1.7% for serious adverse effects. In conclusion, higher doses of aflibercept (>2 mg) are safe and effective for treating nAMD, but further research is needed to analyse the comparison of different high doses and the effect of injection frequency on outcomes.},
}
@article {pmid39991040,
year = {2025},
author = {Gunawardene, AN and Suraneni, S and Rohowetz, LJ and Sridhar, J},
title = {Characteristics and Medical Accuracy of Online Discussions of Retinal Conditions on a Social Media Platform.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251315139},
pmid = {39991040},
issn = {2474-1272},
abstract = {Purpose: To assess the content and medical accuracy of retina-related patient discussions on Reddit, an anonymous social media platform, to better understand the main concerns and reliability of a highly accessible resource. Methods: A cross-sectional analysis was performed of the top 20 posts and top 3 comments from 2011 to 2022 on the Reddit subforums r/Optometry and r/EyeTriage containing the following keywords: "retinal detachment", "macular edema", "macular degeneration", and "diabetic retinopathy". Results: This study assessed 407 posts and comments. Most users who posted were current patients (n = 71 [60.2%]). Most commenters did not specify their identity (n = 172 [59.5%]). A portion of respondents identified as optometrists (n = 51 [17.6%]), and few identified as ophthalmologists (n = 11 [3.8%]). Many statements were medically inaccurate (n = 31 [40.8%]), with pathophysiology comprising the most commonly misunderstood topic (n = 15 [48.4%]). Conclusions: Given the prevalence of inaccurate information and the lack of credibility among Reddit posters, patients should take caution in using these sites for medical guidance regarding retinal conditions.},
}
@article {pmid39990746,
year = {2025},
author = {Chamberlain, CX and Morga, A and Song, Y and Edwards, ML and Anderson, A and Sarathy, K and Christensen, D and Iannaccone, A and Su, J},
title = {Impact of Dry Age-Related Macular Degeneration on Daily Activities and Quality of Life: Interview Findings From Patients and Caregivers Relative to a General Population.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {599-615},
pmid = {39990746},
issn = {1177-5467},
abstract = {PURPOSE: To investigate impacts of dry age-related macular degeneration (AMD) on patients and caregivers.<br><br>PATIENTS AND METHODS: Semi-structured interviews were conducted with patients with dry AMD, caregivers, and controls (individuals without dry AMD, of similar age, sex, and comorbidity profile to patients) between March 2021 and June 2023. Patients aged &#x2265;50 years, with a best corrected visual acuity (BCVA) score from the most recent eye exam after dry AMD diagnosis, were enrolled from the US and UK. Controls with mild visual impairment and unpaid adult caregivers of patients were also enrolled. Main outcomes were functional impairment impact on daily activities, quality of life (QoL), and mental health among patients relative to controls; dry AMD impact on patient daily activities from caregiver perspective; caregiver work productivity, QoL, and burden.<br><br>RESULTS: Thirty patients, 20 controls, and 20 caregivers were interviewed. Patients had a mean age of 65.1 years; 63.3% were female, 83.3% were White, and 96.7% were from the US. Visual impairment based on BCVA score was mild in 70.0% and moderate to severe in 30.0% of patients. Most patients reported problems performing usual activities, whereas most controls experienced no or mild problems. More daily activities in the past month were affected by dry AMD in patients than by visual impairment in controls (mean 4.5 and 2.1), with reading, shopping, and hobbies being most commonly affected in patients. More patients than controls experienced emotional problems. Patients with moderate-to-severe visual impairment reported more impact on activities relative to those with mild visual impairment. Most caregivers were employed, with 46.2% reporting their work productivity was affected at least sometimes, and many experienced mental and emotional burdens and impacts on their daily lives.<br><br>CONCLUSION: Dry AMD impaired the functional ability of patients regardless of visual impairment level and posed significant burdens to caregivers.},
}
@article {pmid39990598,
year = {2025},
author = {Babel, A and Chin, EK and Almeida, D},
title = {Interventional Retrospective Case Series of Patients Undergoing Treatment Intervals of More Than Twenty-Four (24) Weeks With Faricimab.},
journal = {Case reports in ophthalmological medicine},
volume = {2025},
number = {},
pages = {8843375},
pmid = {39990598},
issn = {2090-6722},
abstract = {Purpose: The aim of this study is to evaluate the efficacy and safety of intravitreal faricimab dosing interval at and beyond 24 weeks in patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). Methods: This study is a retrospective case series of eight patients with persistent DME and nAMD who received intravitreal faricimab at and beyond the 24-week (6-month) dosing interval regimen. Results: The majority of patients experienced an improved mean best-corrected visual acuity (BCVA) of 9.9 letters; congruent anatomical improvement (mean central macular thickness (CMT)) decrease of 44 μm on optical coherence tomography (OCT) is demonstrated at 6 months despite extended faricimab dosing intervals. Conclusions: Extended intravitreal faricimab dosing intervals at and beyond 24 weeks maintained visual and anatomical outcomes in patients over 1 year. This suggests the feasibility of personalized extended dosing tailored to each patient's disease activity, potentially reducing treatment burden.},
}
@article {pmid39990324,
year = {2025},
author = {Colasanti, JJ and Lin, JB and Terao, R and Lee, TJ and Santeford, A and Apte, RS},
title = {MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.12.637499},
pmid = {39990324},
issn = {2692-8205},
abstract = {UNLABELLED: Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is unclear. In an injury-induced murine CNV model, we discovered miR-34a promoted pathological angiogenesis, without altering expression of Vegfa or its receptor Kdr, the canonical regulators of CNV. Mechanistically, miR-34a directly targets and inhibits the transcription factor KLF2 thereby upregulating the pro-angiogenic factors CXCR4 and CXCL12. Finally, we show miR-34a exacerbates CNV in aged mice and is expressed in CNV lesions excised from wet AMD patients. These findings establish a causal link between the age-related miR-34a and neovascularization in AMD.<br><br>TEASER: Identification of a molecular mechanism involved in the pathogenesis of a prevalent and debilitating age-related ocular disease.},
}
@article {pmid39987980,
year = {2025},
author = {Berni, A and Kastner, JD and Shen, M and Cheng, Y and Herrera, G and Hiya, F and Liu, J and Wang, L and Li, J and El-Mulki, OS and Beqiri, S and Trivizki, O and Waheed, NK and O'Brien, R and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Hyperreflective Foci Along the Retinal Pigment Epithelium Predict the Onset of Large Choroidal Hypertransmission Defects in Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {274},
number = {},
pages = {76-90},
pmid = {39987980},
issn = {1879-1891},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; Female ; Male ; Retrospective Studies ; Aged ; Prospective Studies ; Aged, 80 and over ; Fluorescein Angiography/methods ; Disease Progression ; *Choroid/pathology ; *Macular Degeneration/diagnosis ; Visual Acuity ; Follow-Up Studies ; Middle Aged ; *Choroid Diseases/diagnosis ; },
abstract = {PURPOSE: In eyes with intermediate age-related macular degeneration (iAMD), we separately quantified the hyperreflective foci (HRF) along the retinal pigment epithelium (rpeHRF) and the intraretinal HRF (iHRF) to determine if the location of the HRF predicted the progression from iAMD to the onset of large persistent choroidal hypertransmission defects (hyperTDs).<br><br>DESIGN: Post hoc subgroup cohort analysis of a prospective study.<br><br>METHODS: A retrospective analysis was performed on a prospective natural history database of eyes with AMD imaged using swept-source optical coherence tomography (SS-OCT). En face images derived from choroidal slabs positioned 64 to 400 &#xb5;m beneath Bruch membrane were used with a semiautomated algorithm to identify and quantify hypotransmission defects (hypoTDs) attributable to either iHRF or rpeHRF within a 5-mm fovea-centered circle. iHRF were identified on corresponding B-scans as hyperreflective lesions within the neurosensory retina, and rpeHRF were identified as areas of retinal pigment epithelium thickening. Multivariable survival analysis was performed to determine if the area measurements of either iHRF or rpeHRF were more likely to predict the onset of the first large persistent hyperTD.<br><br>RESULTS: Of the 171 eyes with iAMD included in this study, 82 (48%) developed at least 1 large hyperTD during a median follow-up of 59.1 months. Univariable Cox regression analyses showed that rpeHRF area (P < .001), iHRF area (P = .003), and drusen volume (P < .001) were all significantly associated with the onset of the first large persistent hyperTD. However, a multivariable Cox regression model showed that only the rpeHRF area remained a significant predictor of disease progression (P < .001).<br><br>CONCLUSIONS: In iAMD eyes, the area of rpeHRF was more predictive of disease progression than either the drusen volume or iHRF, which suggests that these rpeHRF serve as harbingers of focal atrophy formation and may predict where hyperTDs form.},
}
@article {pmid39986639,
year = {2025},
author = {Magrath, G and Luvisi, J and Russakoff, D and Oakley, J and Say, EA and Blice, J and Jayagopal, A and Tucker, S and Loayza, A and Baker, GH and Obeid, JS},
title = {Use of a Convolutional Neural Network to Predict the Response of Diabetic Macular Edema to Intravitreal Anti-VEGF Treatment: A Pilot Study.},
journal = {American journal of ophthalmology},
volume = {273},
number = {},
pages = {176-181},
doi = {10.1016/j.ajo.2025.02.017},
pmid = {39986639},
issn = {1879-1891},
mesh = {Humans ; *Macular Edema/drug therapy/diagnosis/etiology ; Intravitreal Injections ; *Diabetic Retinopathy/drug therapy/diagnosis/complications ; Pilot Projects ; Tomography, Optical Coherence ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Retrospective Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Female ; Male ; *Neural Networks, Computer ; Visual Acuity/physiology ; Middle Aged ; *Bevacizumab/therapeutic use/administration &amp; dosage ; Aged ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Follow-Up Studies ; Treatment Outcome ; Convolutional Neural Networks ; },
abstract = {PURPOSE: To utilize a convolutional neural network (CNN) to predict the response of treatment-naïve diabetic macular edema (DME) to a single injection of anti-vascular endothelial growth factor (anti-VEGF) with data from optical coherence tomography (OCT).<br><br>DESIGN: Retrospective study performed via chart review.<br><br>METHODS: Setting: This was a single-center study performed at the Storm Eye Institute, Medical University of South Carolina.<br><br>PATIENT POPULATION: Patients with a new diagnosis of DME who underwent intravitreal (IVT) anti-VEGF injections were eligible for inclusion, provided they had a baseline OCT scan at the time of diagnosis and a 1-month follow-up OCT scan after the first anti-VEGF injection. Exclusion criteria included prior treatment with anti-VEGF, lack of required OCT scans, coexistent macular degeneration, and macular edema due to other retinal diseases. Seventy-three (73) eyes from 53 patients were included.<br><br>INTERVENTION: The OCT scan from the baseline visit was compared to the follow-up OCT scan approximately 1 month after the first anti-VEGF injection to determine change in central subfield thickness (delta CST). The delta CST was fed into the CNN as a label to train the system to predict treatment response from only the baseline OCT scan.<br><br>MAIN OUTCOME MEASURE: CNN prediction of treatment response to anti-VEGF. Treatment response was defined as a CST reduction of 10 &#xb5;m or more.<br><br>RESULTS: Based on delta CST from 2 OCT scans, 57 eyes were responders and 16 eyes were non-responders to the initial anti-VEGF injection. Analyzing only the baseline OCT scan for each eye, the trained CNN demonstrated an area under the curve (AUC) of 0.81. At the reported operating point, the CNN correctly identified 45 of the 57 responder eyes (i.e., recall of 78.9%) and 11 of the 16 non-responder eyes (i.e., specificity of 68.8%).<br><br>CONCLUSIONS: The results of this study demonstrate the potential of a CNN to predict the response of treatment-na&#xef;ve DME to a single injection of anti-VEGF therapy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.},
}
@article {pmid39986366,
year = {2025},
author = {Skowronska-Krawczyk, D and Finnemann, SC and Grant, MB and Held, K and Hu, Z and Lu, YR and Malek, G and Sennlaub, F and Sparrow, J and D'Amore, PA},
title = {Features that distinguish age-related macular degeneration from aging.},
journal = {Experimental eye research},
volume = {254},
number = {},
pages = {110303},
pmid = {39986366},
issn = {1096-0007},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY012601/EY/NEI NIH HHS/United States ; K99 EY034938/EY/NEI NIH HHS/United States ; R01 EY035126/EY/NEI NIH HHS/United States ; R01 EY032753/EY/NEI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY032751/EY/NEI NIH HHS/United States ; R01 EY026539/EY/NEI NIH HHS/United States ; R01 EY034003/EY/NEI NIH HHS/United States ; U01 EY034594/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/physiopathology/metabolism/genetics/diagnosis ; *Aging/physiology ; Animals ; Retinal Pigment Epithelium/pathology ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are observed in aging tissues including a low level of chronic inflammation (inflammaging), changed lipid and energy metabolism, and senescence. Nevertheless, whereas everyone ages, only a subset of the population develops AMD. The purpose of this review is to delineate the differences on a cellular and molecular level between natural aging changes and those observed in AMD. We provide a unique perspective on how genetic and environmental components modulate aging in the eye, as well as the specific role of the aging RPE and retina in the pathogenesis of AMD. Topics discussed include the mechanism of aging and its relation to the mechanism of AMD, current animal models that can be used to recapitulate some aspects of the pathology, and potential interventions that shift the balance towards healthy aging and therefore attenuate, prevent or delay the initiation of the disease.},
}
@article {pmid39985055,
year = {2025},
author = {Vitillo, L and Anjum, F and Hewitt, Z and Laing, O and Ababneh, NA and Baker, D and Barbaric, I and Coffey, PJ},
title = {Gain of 20q11.21 in human pluripotent stem cells enhances differentiation to retinal pigment epithelium.},
journal = {Stem cell research &amp; therapy},
volume = {16},
number = {1},
pages = {82},
pmid = {39985055},
issn = {1757-6512},
support = {MR/L012537/1//UK Regenerative Medicine Platform/ ; MR/R015724/1//UK Regenerative Medicine Platform/ ; G1000730/MRC_/Medical Research Council/United Kingdom ; Grant No. 2022/19//Deanship of Scientific Research, University of Jordan/ ; P12761//Lincy Foundation/ ; G1000730//California Institute of Regenerative Medicine/ ; Grant No. 8/2019//King Abdullah II Design and Development Bureau/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/cytology/metabolism ; *Cell Differentiation/genetics ; *Pluripotent Stem Cells/metabolism/cytology ; bcl-X Protein/metabolism/genetics ; Animals ; Mice ; },
abstract = {BACKGROUND: Cell therapies based on human pluripotent stem cells (hPSCs) are in clinical trials with the aim of restoring vision in people with age-related macular degeneration. The final cell therapy product consists of retinal pigment epithelium (RPE) cells differentiated from hPSCs. However, hPSCs recurrently acquire genetic abnormalities that give them an advantage in culture with unknown effects to the clinically-relevant cell progeny. One of the most common genetic abnormalities in hPSCs is the sub-karyotype 20q11.21 copy number variant, known to carry oncogenes. Understanding the impact of this variant on RPE differentiation and its potential for malignant transformation is crucial for the development of safe and effective cell therapies.<br><br>METHODS: We monitored the RPE differentiation efficiency of hPSCs with or without the 20q11.21 variant. We then phenotyped the purified RPE cells for functionality, purity and tumorigenicity potential.<br><br>RESULTS: We observed that 20q11.21 clones exhibited an enhanced differentiation capacity, developing pigmented foci at a higher rate and yield compared to normal clones. Gene expression analysis confirmed the upregulation of key RPE markers in 20q11.21 clones. The enhanced differentiation capacity of 20q11.21 clones was found to be dependent on the activity of BCL-XL, located within the amplicon. Furthermore, we demonstrated that 20q11.21-containing RPE cells displayed a mature phenotype, maintained long-term stability, and exhibited no malignant transformation capacity in vitro.<br><br>CONCLUSION: We demonstrated that gain of 20q11.21 enhances the speed and yield of RPE differentiation without compromising the phenotype of the derivatives. Finally, we discovered that 20q11.21-localised BCL-XL is important for RPE differentiation with potential non-canonical roles in retinal biology.},
}
@article {pmid39984833,
year = {2025},
author = {Yang, B and Yang, K and Chen, Y and Li, Q and Chen, J and Li, S and Wu, Y},
title = {Exposure of A2E to blue light promotes ferroptosis in the retinal pigment epithelium.},
journal = {Cellular &amp; molecular biology letters},
volume = {30},
number = {1},
pages = {22},
pmid = {39984833},
issn = {1689-1392},
support = {82471093//National Natural Science Foundation of China/ ; },
mesh = {*Ferroptosis/radiation effects/drug effects ; *Retinal Pigment Epithelium/metabolism/radiation effects/pathology ; Animals ; *Retinoids/metabolism/pharmacology ; *Light ; Mice ; Reactive Oxygen Species/metabolism ; Lipid Peroxidation/radiation effects ; Mice, Knockout ; Macular Degeneration/pathology/metabolism ; Lipofuscin/metabolism ; Humans ; Mice, Inbred C57BL ; Iron/metabolism ; ATP-Binding Cassette Transporters/metabolism/genetics ; Blue Light ; },
abstract = {BACKGROUND: Age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) is closely related to the etiology of autosomal recessive Stargardt's disease (STGD1) and dry age-related macular degeneration (AMD). N-retinylidene-N-retinylethanolamine (A2E) is a leading component of RPE lipofuscin that is highly susceptible to blue light. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the accumulation of lipid peroxides to a lethal level, which plays an important role in retinal diseases. However, it remains unknown whether A2E functions as a physiological trigger for eliciting blue light-induced ferroptosis of RPE cells.<br><br>METHODS: A2E-loaded RPE cells and Abca4[-/-]Rdh8[-/-] mice were exposed to blue light, respectively. Western blotting, immunofluorescence staining, reactive oxygen species (ROS) staining, intracellular iron staining, lipid peroxidation staining, fundus imaging, optical coherence tomography (OCT), hematoxylin-eosin (HE) staining, and electroretinography (ERG) were utilized to elucidate the role of blue light in A2E induced ferroptosis in the RPE and its potential mechanisms.<br><br>RESULTS: Exposure of A2E to blue light promoted ferroptotic cell death in RPE cells by elevating ferrous ion (Fe[2+]) levels and inhibiting the solute carrier family 7 membrane 11 (SLC7A11)-glutathione&#xa0;(GSH)-glutathione peroxidase 4 (GPX4) axis. GPX4 inactivation and ROS generated by Fe[2+]&#xa0;overload and&#xa0;GSH depletion precipitated&#xa0;lipid peroxidation&#xa0;and subsequent ferroptosis in A2E-containing RPE cells upon exposure to blue light. In addition to GSH supplement, repressing either Fe[2+]&#xa0;by deferiprone (DFP) or lipid peroxidation with ferrostatin-1 (Fer-1) significantly protected RPE cells against ferroptosis caused by blue light illumination of A2E.&#xa0;Abca4[-/-]Rdh8[-/-]&#xa0;mice featured by an accelerated deposition of A2E in the RPE is an&#xa0;animal model&#xa0;for STGD1 and dry AMD. It was observed that ferroptosis was indeed present in the RPE of&#xa0;Abca4[-/-]Rdh8[-/-]&#xa0;mice following exposure to blue light. Notably, alleviating ferroptosis by intraperitoneally injected Fer-1 effectively rescued retinal function and ameliorated RPE/photoreceptor degeneration in blue light-exposed&#xa0;Abca4[-/-]Rdh8[-/-]&#xa0;mice.<br><br>CONCLUSIONS: Our results suggest the importance of blue light in A2E-mediated ferroptosis in the RPE, and deeply broaden the understanding of mechanisms underlying RPE atrophy arising from lipofuscin accumulation in STGD1 and dry AMD.},
}
@article {pmid39984700,
year = {2025},
author = {Chandak, S and Gurudas, S and Pakeer, RM and Kazantzis, D and Ghanchi, F and Grabowska, A and Talks, SJ and Pearce, I and McKibbin, M and Kotagiri, A and Menon, G and Burton, BJ and Gale, R and Sivaprasad, S},
title = {Factors associated with achieving various visual acuity outcomes during loading doses of aflibercept 2 mg for treatment naïve exudative age-related macular degeneration: PRECISE Study Report 7.},
journal = {Eye (London, England)},
volume = {39},
number = {8},
pages = {1553-1561},
pmid = {39984700},
issn = {1476-5454},
support = {SIVS1045//Boehringer Ingelheim/ ; },
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity/physiology ; Female ; Aged ; Male ; Tomography, Optical Coherence ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Fluorescein Angiography ; Treatment Outcome ; Middle Aged ; },
abstract = {PURPOSE: To identify demographic and baseline OCT characteristics that are predictive of VA outcomes after the first and post-loading injections in patients treated with 2 mg aflibercept.<br><br>METHODS: This study evaluated VA outcomes in 1999 eyes of 1862 patients with nAMD initiated on aflibercept therapy. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA outcome defined as VA&#x2009;&#x2265;&#x2009;68 ETDRS letters (Snellen&#x2009;&#x2265;&#x2009; 6/12) and poor VA outcome of <54 ETDRS letters (Snellen&#x2009;<&#x2009;6/18) or a loss of &#x2265;5 ETDRS letters after first and post-loading injections were analysed using logistic regression via generalised estimating equations.<br><br>RESULTS: The mean age was 79.3 (SD 7.8) years, 1126 (60.5%) were females, and predominantly white ethnic background (1772 [95.2%]). The mean presenting VA was 58.0 (SD 14.5) ETDRS letters. After the loading phase, 930/1994 (46.6%) eyes achieved VA&#x2009;&#x2265;&#x2009;68 ETDRS letters, and 457 (22.9%) attained VA&#x2009;<&#x2009;54 ETDRS letters. Increasing age, non-white ethnicity, and baseline VA&#x2009;<&#x2009;54 letter score is associated with VA&#x2009;<&#x2009;54 letters. The OCT parameters associated with reduced odds of VA&#x2009;&#x2265;&#x2009;68 ETDRS letters and increased odds of VA&#x2009;<&#x2009;54 ETDRS letters after first and post-loading phase included fovea-involving intraretinal fluid, all types of macular neovascularisation (MNV) versus type 1 MNV, fovea-involving MNV (vs. non-foveal MNV), subfoveal MNV complex, increased central subfield thickness, foveal presence of subretinal hyper-reflective material, atrophy, fibrosis, ungradable or ellipsoid zone and/or external limiting membrane loss.<br><br>CONCLUSION: This study could provide individual-level visual prognosis about their post-loading VA based on demography, VA and OCT characteristics at presentation.},
}
@article {pmid39984146,
year = {2025},
author = {Parra-Sánchez, &#xc1; and Martínez-Navarrete, G and Accomasso, G and Chindamo, G and Chirio, D and Peira, E and Sapino, S and Bernabeu-Zornoza, A and Gombau-García, A and Gallarate, M and Fernández, E},
title = {A novel bevacizumab delivery system using solid lipid nanoparticles for potential wet age-related macular degeneration treatment: An in vivo study.},
journal = {International journal of pharmaceutics},
volume = {673},
number = {},
pages = {125379},
doi = {10.1016/j.ijpharm.2025.125379},
pmid = {39984146},
issn = {1873-3476},
mesh = {Animals ; *Bevacizumab/administration &amp; dosage/chemistry ; *Angiogenesis Inhibitors/administration &amp; dosage/chemistry ; *Nanoparticles/chemistry/administration &amp; dosage ; *Lipids/chemistry ; Rats, Inbred BN ; Rats ; Male ; Drug Liberation ; Drug Delivery Systems ; *Wet Macular Degeneration/drug therapy ; Choroidal Neovascularization/drug therapy ; Intravitreal Injections ; Disease Models, Animal ; Tomography, Optical Coherence ; Delayed-Action Preparations ; Liposomes ; },
abstract = {Degenerative ocular diseases such as age-related macular degeneration (AMD) are typically treated with intravitreal (IVT) injections of anti-VEGF antibodies such as bevacizumab (BVZ). However, frequent IVT injections are associated with significant risks, including adverse effects and low patient compliance. This paper proposes solid lipid nanoparticles (SLNs) as an innovative drug delivery system to address these challenges. Indeed, SLNs offer advantages such as improved stability and prolonged release of the loaded compounds. After assessing BVZ prolonged release from SLNs by in vitro release studies, accurate in vivo studies were performed in a laser-induced CNV model in Brown Norway rats. The aim was to evaluate the efficacy of BVZ-SLNs in comparison to conventional treatments like Avastin®. Techniques including optical coherence tomography (OCT) were employed to assess the potential neovascularization inhibition. The results show that BVZ-SLNs administration can significantly decrease vascular density, even with a difference of 3.7% with Avastin®. Overall, the findings underscore SLNs as a promising platform for ocular drug delivery offering a valid strategy for enhanced therapeutic efficacy and patient compliance in the treatment of degenerative ocular pathologies.},
}
@article {pmid39984014,
year = {2025},
author = {Xia, F and Wang, L and Ji, Y and Wang, Z and Feng, Y and Liao, H and Pan, X and Li, S and Zhu, W and Tian, J and Tong, X and Ma, J},
title = {Capilliposide A relieved dry age-related macular degeneration through ROS/SIRT1/P53 signaling pathway.},
journal = {European journal of pharmacology},
volume = {995},
number = {},
pages = {177412},
doi = {10.1016/j.ejphar.2025.177412},
pmid = {39984014},
issn = {1879-0712},
mesh = {*Sirtuin 1/metabolism ; Animals ; *Reactive Oxygen Species/metabolism ; *Tumor Suppressor Protein p53/metabolism ; Signal Transduction/drug effects ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology/chemically induced ; Mice ; Cell Line ; *Saponins/pharmacology/therapeutic use ; Apoptosis/drug effects ; Male ; Disease Models, Animal ; Cell Survival/drug effects ; Retinal Pigment Epithelium/drug effects/pathology ; Mice, Inbred C57BL ; },
abstract = {Age-related macular degeneration (AMD) is the main cause of vision impairment in the elderly, which still lacks efficient treatment. Capilliposide A (LC-A), a saponin-type anti-inflammation compound extracted from Lysimachia capillipes Hemsl, were used for investigating its anti-AMD effects. The cell viability of LC-A against ARPE-19 cell lines were detected by CCK8 assay. Flow cytometry assay was used for examining ROS accumulation and apoptosis. Dry AMD mice model was constructed by NaIO3 (i.v.). Then, the anti-AMD effects of LC-A were detected by optical coherence tomography (OCT) assay, electroretinogram (ERG) assay, H&amp;E staining assay and immunofluorescence staining assay. Transcriptome analysis was used to screen the potential signaling pathway of LC-A treatment. Furthermore, Western Blot and immunofluorescence assay were used to verify the signaling pathway in vivo and in vitro. LC-A performed safety against ARPE-19 cell lines (under 25 μM). LC-A also showed significant inhibitory effects against apoptosis and ROS accumulation caused by NaIO3. Meanwhile, AMD mice model was significantly relieved by LC-A eye-drop treatment. Then, P53 signaling pathways influenced by LC-A was screened out by transcriptome. Results showed that LC-A could inhibit SIRT1/P53 protein expression levels verified by immunofluorescence and Western Blot. These results indicated that LC-A could inhibit apoptosis and ROS accumulation caused dry AMD through SIRT1/P53 signaling pathways, which showed clinical potential for treating senescence-related or SIRT1/P53 mediated AMD patients.},
}
@article {pmid39983974,
year = {2025},
author = {Miller, JML and Thompson, BR and Handa, JT and Luthert, P and Chakravarthy, U and Csaky, KG and Bird, A and Young, BK and Iyengar, SK and Baek, J and Zouache, MA and Richards, BT and Hageman, GS and Rodrigues, G and Bharti, K and Flannery, JG and Gorin, MB and Bowes Rickman, C},
title = {Dissecting the biological complexity of age-related macular degeneration: Is it one disease, multiple separate diseases, or a spectrum?.},
journal = {Experimental eye research},
volume = {254},
number = {},
pages = {110304},
pmid = {39983974},
issn = {1096-0007},
support = {U01 MH116442/MH/NIMH NIH HHS/United States ; RC2 AG036607/AG/NIA NIH HHS/United States ; R01 EY027004/EY/NEI NIH HHS/United States ; R01 EY022310/EY/NEI NIH HHS/United States ; R01 EY027691/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; R01 AG067025/AG/NIA NIH HHS/United States ; IK6 BX005233/BX/BLRD VA/United States ; I01 BX004557/BX/BLRD VA/United States ; IK6 BX005787/BX/BLRD VA/United States ; R01 AG065582/AG/NIA NIH HHS/United States ; R01 MH125246/MH/NIMH NIH HHS/United States ; I01 BX003364/BX/BLRD VA/United States ; K08 MH122911/MH/NIMH NIH HHS/United States ; R01 EY019904/EY/NEI NIH HHS/United States ; R01 EY035805/EY/NEI NIH HHS/United States ; R01 AG050986/AG/NIA NIH HHS/United States ; P30 EY005722/EY/NEI NIH HHS/United States ; K08 EY033420/EY/NEI NIH HHS/United States ; R01 EY032609/EY/NEI NIH HHS/United States ; I01 BX004189/BX/BLRD VA/United States ; },
mesh = {Humans ; *Macular Degeneration/genetics/classification/diagnosis ; Disease Progression ; },
abstract = {Clinicians recognize the heterogeneity of age-related macular degeneration (AMD) in presentation, progression, and treatment response, as well as the challenges in distinguishing it from other macular degenerations. As part of the 2024 Ryan Initiative for Macular Research meeting, a group of clinician-scientists and basic scientists were convened to consider the question of whether AMD should be classified as a single disorder or a spectrum of conditions. To answer this question, we reviewed research on several "dimensions" that constitute AMD risk or pathogenesis: genetics, ancestry, retinal imaging findings, diet and environment, aging, and outer retinal molecular and cellular pathways. The group reached a consensus that AMD represents a heterogeneous collection of disease states arising from the interplay of these dimensions. This heterogeneity can be conceived of as a "cloud" of AMD phenotypes. Defining subtypes within this "cloud" requires longitudinal cohorts of well-genotyped and phenotyped patients who progress from no AMD through late AMD, analyzed by unsupervised learning. Comparing the AMD subtypes that emerge from this analysis, especially -omics data from each subtype, will illuminate biology that is applicable to certain subtypes of AMD patients and molecular pathogenic mechanisms that universally apply to all AMD. This knowledge will, in turn, drive improved drug development.},
}
@article {pmid39983511,
year = {2025},
author = {Qu, Y and Zhang, G and Jiang, Y and Hu, W and Meng, X and Chen, R and Gao, S and Wu, Z and Sun, X and Jia, H},
title = {Increasing residential greenness attenuates the hazard of ultraviolet radiation on age-related macular degeneration in the elderly: A nationwide study in China.},
journal = {Ecotoxicology and environmental safety},
volume = {292},
number = {},
pages = {117924},
doi = {10.1016/j.ecoenv.2025.117924},
pmid = {39983511},
issn = {1090-2414},
mesh = {Humans ; China/epidemiology ; *Macular Degeneration/epidemiology ; *Ultraviolet Rays/adverse effects ; Aged ; Male ; Female ; *Environmental Exposure/statistics &amp; numerical data ; Middle Aged ; Incidence ; },
abstract = {BACKGROUND: Exposure to ultraviolet (UV) radiation may increase the risk of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. However, prevention measures of UV radiation at population-level remain lacking, exacerbating the health inequity. Given the protective effect of residential greenness on human health, we aim to identify the impact of greenness on the UV-AMD association.<br><br>METHODS: We used data from 19,832 participants in a national cohort in China conducted from 2018 to 2023. Satellite-based models and ophthalmological fundus images were used to evaluate the exposures (UV radiation and residential greenness) and outcome (incident AMD), respectively. The effects of UV radiation, residential greenness, and their interplay on incident AMD were furtherly estimated through multiple Cox proportional hazard models.<br><br>RESULTS: A total of 3800 incident AMD cases were diagnosed during follow-up. Higher UV radiation elevated the hazard of incident AMD, while excessive greenness showed a significant protective effect, with hazard ratios of 1.35 (1.29, 1.41) and 0.90 (0.86, 0.94) for per tertile increment, respectively. These relationships remained consistent in two-exposure models, and a significant modification effect of greenness on the UV-AMD association was observed. Notably, when the residential greenness over 0.4, the hazard of UV on incident AMD became non-significant. This greenness threshold remained consistent across rural-urban and south-north subgroups.<br><br>CONCLUSION: Maintaining the residential greenness above 0.4, as a low-cost measure at population-level, could mitigate the UV-AMD association and facilitate the health equity in China, regardless of the regions.},
}
@article {pmid39981531,
year = {2025},
author = {Goto, Y and Kuniyoshi, K and Goto, K and Kayazawa, T and Kominami, T and Mano, F and Sakamoto, M and Iwahashi, C and Kusaka, S},
title = {Development of Macular Atrophy after Macular Hole Surgery in an Eye with Retinitis Pigmentosa.},
journal = {Case reports in ophthalmology},
volume = {16},
number = {1},
pages = {107-113},
pmid = {39981531},
issn = {1663-2699},
abstract = {INTRODUCTION: Macular hole is a rare complication in patients with retinitis pigmentosa that significantly reduces visual acuity. Although vitreous surgery for macular holes generally yields favorable outcomes, postoperative macular atrophy has been reported. We report the second case of retinitis pigmentosa in a patient who developed a 13-year progressive macular atrophy after macular hole surgery.<br><br>CASE PRESENTATION: A 64-year-old Japanese woman, who had been diagnosed with retinitis pigmentosa at 52 years of age, presented to our hospital with blurred vision in her left eye. Phacovitrectomy of the left eye was performed after a full-thickness macular hole was revealed by optical coherence tomography. We stained the internal limiting membrane during surgery using 0.05% indocyanine green and peeled it around the macular hole. Nevertheless, slight atrophy of the retinal pigment epithelium appeared in the left macula 17 days after surgery. The macular hole closed 1 year after surgery, and the macular atrophy gradually became more apparent and enlarged. Thirteen years later, atrophy had expanded to 2.5-disc diameters, and the left decimal best-corrected visual acuity was 0.1; no macular degeneration appeared in the right eye. Genetic examination revealed compound heterozygous variants in the EYS gene.<br><br>CONCLUSION: Macular atrophy can develop after dye-assisted macular hole surgery for patients with retinitis pigmentosa. Potential risk factors for the development of postoperative macular atrophy include dye toxicity, light toxicity, surgical intervention in the macula, postoperative inflammation, and genotype. However, the exact cause of atrophy remains uncertain.},
}
@article {pmid39981241,
year = {2025},
author = {Armento, A and Sonntag, I and Almansa-Garcia, AC and Sen, M and Bolz, S and Arango-Gonzalez, B and Kilger, E and Sharma, R and Bharti, K and Fernandez-Godino, R and de la Cerda, B and Clark, SJ and Ueffing, M},
title = {The AMD-associated genetic polymorphism CFH Y402H confers vulnerability to Hydroquinone-induced stress in iPSC-RPE cells.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1527018},
pmid = {39981241},
issn = {1664-3224},
mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/drug effects ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Macular Degeneration/genetics/metabolism/pathology ; *Complement Factor H/genetics ; *Oxidative Stress/drug effects ; *Hydroquinones/toxicity/pharmacology ; Genetic Predisposition to Disease ; *Polymorphism, Single Nucleotide ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD), a degenerative disease of the macula, is caused by an interplay of diverse risk factors (genetic predisposition, age and lifestyle habits). One of the main genetic risks includes the Y402H polymorphism in complement Factor H (FH), an inhibitor of complement system activation. There has been, and continues to be, much discussion around the functional consequences of this Y402H polymorphism, whether the soluble FH protein confers its risk association, or if the cells expressing the protein themselves are affected by the genetic alteration. In our study, we examined the cell characteristics of the retinal pigment epithelium (RPE) cells, which play a major role in retinal homeostasis and stability and which are synonymously linked to AMD.<br><br>METHODS: Here, we employ RPE cells derived from induced pluripotent stem cells (iPSC) generated from donors, carrying either homozygous 402Y (low risk) or 402H (high risk) variants of the CFH gene. RPE cells were treated with Hydroquinone (HQ), a component of cigarette smoke, to induce oxidative damage.<br><br>RESULTS: Intriguingly, RPE cells carrying high genetic risk proved more vulnerable to oxidative insult when exposed to HQ, as demonstrated by increased cytotoxicity and caspase activation, compared to the low-risk RPE cells. The exposure of RPE cells to RPE conditioned medium, normal human serum (NHS) and inactivated NHS (iNHS) had minimal impact on cell cytotoxicity and caspase activation, nor did the presence of purified soluble FH rescue the observed effects. Considering the known connection of oxidative stress to proteotoxic stress and degrading processes, we investigated the unfolded protein response (UPR) and autophagy. When exposed to HQ, RPE cells showed an increase in autophagy markers; however, iPSC-RPE cells carrying high genetic risk showed an overall reduced autophagic flux.<br><br>DISCUSSION: Our findings suggest that the degree of cellular susceptibility to oxidative stress is not conferred by soluble FH protein and other complement sources, but intercellularly because of the corresponding genetic risk predisposition. Our data support the hypothesis that RPE cells carrying high genetic risk are less resilient to oxidative stress.},
}
@article {pmid39980175,
year = {2025},
author = {Neveu, MM and Chong, V and Empeslidis, T and Scholl, HPN and Robson, AG},
title = {Electrodiagnostic Tests as Potential Efficacy Endpoints in Clinical Trials of Novel Pharmacological Therapies for Acquired Retinal Disorders.},
journal = {Ophthalmic research},
volume = {68},
number = {1},
pages = {169-186},
doi = {10.1159/000544702},
pmid = {39980175},
issn = {1423-0259},
mesh = {Humans ; *Evoked Potentials, Visual/physiology ; *Retinal Diseases/drug therapy/diagnosis/physiopathology ; *Clinical Trials as Topic ; Electroretinography/methods ; Visual Acuity ; *Retina/physiopathology ; *Electrodiagnosis/methods ; },
abstract = {BACKGROUND: Electrodiagnostic tests (EDTs) provide non-invasive, objective, and measurable indications of retinal and visual pathway function. These hold the promise of evaluating drug efficacy and disease progression over shorter periods than traditional "end-stage" outcome measures (e.g., best-corrected visual acuity) in various ophthalmological pathologies. The International Society for Clinical Electrophysiology of Vision has defined rigorous standards for EDTs, intended to optimize diagnostic power, enabling meaningful inter-laboratory comparisons and facilitating application as outcome measures in increasing numbers of multicentre clinical trials.<br><br>SUMMARY: This review outlines the main EDTs, including full-field, pattern, and multifocal electroretinography; the electro-oculogram; and the cortical visual-evoked potential, and highlights the possible role for monitoring disease progression and assessing treatment safety and efficacy. The utility and potential of EDTs are highlighted in studies that have assessed function and tested or monitored treatment safety or efficacy for a range of acquired retinal and optic nerve disorders, including central retinal vein occlusion, diabetic retinopathy, glaucoma, age-related macular degeneration, posterior uveitis, and autoimmune-related retinopathies.<br><br>KEY MESSAGES: EDTs are fundamental to the diagnosis and phenotyping of many acquired retinal and visual pathway disorders. They also provide methods for the objective assessment of the efficacy and safety of potential novel treatments across short periods. Conventional psychophysical tests, such as visual acuity, are of limited value in localizing and characterizing dysfunction and are not always suitable for monitoring purposes. This review highlights where EDTs may address the need for better outcome measures to evaluate novel treatments within clinical trials, helping to select early treatment candidates and for the assessment of safety and efficacy.},
}
@article {pmid39979822,
year = {2025},
author = {Wang, R and Liu, Y and Zhang, Y and Yi, Q and Xiao, W and Wang, T and Chen, Q and Xiang, J and Song, L and Li, C and Li, F and Liu, L and Li, Q and Fan, C and Mao, X and Zuo, X},
title = {DNA Framework-Enabled Ocular Barrier Penetration for Microinvasive Antiangiogenic Therapy.},
journal = {Journal of the American Chemical Society},
volume = {147},
number = {9},
pages = {7545-7554},
doi = {10.1021/jacs.4c16529},
pmid = {39979822},
issn = {1520-5126},
mesh = {*Angiogenesis Inhibitors/pharmacology/chemistry/administration &amp; dosage/therapeutic use ; Animals ; Mice ; *Choroidal Neovascularization/drug therapy/pathology ; *Aptamers, Nucleotide/chemistry/pharmacology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Humans ; *DNA/chemistry ; *Blood-Retinal Barrier/metabolism/drug effects ; },
abstract = {Therapeutic aptamers targeting vascular endothelial growth factor A (VEGFA) have advanced the development of antiangiogenic drugs for treating choroidal neovascularization (CNV) diseases. However, despite FDA approval for use in neovascular age-related macular degeneration (nAMD), the effective in vivo delivery of therapeutic aptamers is hindered by ocular barriers and rapid degradation in biofluids. Here, we demonstrated a microinvasive delivery of VEGFA-targeted aptamers to the ocular fundus using tetrahedral framework nucleic acids (tFNAs). Upon incorporating anti-VEGFA aptamers to the tFNAs (apt-tFNA), we interrogated their penetration across the outer blood-retinal barrier (oBRB) to the innermost retinal in the eyeball, while maintaining their structural integrity. In addition, the apt-tFNA showed superior efficacy in inhibiting vascular proliferation and migration by neutralizing VEGFA. Furthermore, in a laser-induced CNV mouse model, subconjunctival injection of apt-tFNA exhibited comparable antiangiogenic efficacy to intravitreal ranibizumab, a monoclonal antibody fragment. These findings suggest that FNAs can effectively deliver therapeutic aptamers to the ocular fundus without compromising their antiangiogenic properties, highlighting their potential for microinvasive and feasible periocular administration in treating neovascular ophthalmic diseases.},
}
@article {pmid39979609,
year = {2025},
author = {Ibrahim, FN and Sivaprasad, S and Cheung, CMG},
title = {Gender and ethnic diversity in randomised clinical trials in age-related macular degeneration and diabetic macular oedema.},
journal = {Eye (London, England)},
volume = {39},
number = {7},
pages = {1249-1253},
pmid = {39979609},
issn = {1476-5454},
mesh = {Female ; Humans ; Male ; *Diabetic Retinopathy/ethnology/therapy ; *Ethnicity/statistics &amp; numerical data ; *Macular Degeneration/ethnology/therapy ; *Macular Edema/ethnology/therapy ; Patient Selection ; *Randomized Controlled Trials as Topic ; Sex Factors ; Minority Groups/statistics &amp; numerical data ; },
abstract = {In recent years, there has been increasing recognition of the importance of diversity in pivotal randomised clinical trials (RCTs). This is vital to ensure the validity and applicability of the results in the clinical setting. In this review, we aim to assess the inclusion of females and minoritized groups in recent RCTs in age-related macular degeneration (AMD) and diabetic macular oedema (DMO) and explore any potential barriers to their enrolment. Overall, a female predominance was observed among the AMD RCTs while less than half of the study population in DMO trials were females. White participants made up the majority of the study population in both AMD and DMO trials. Gender distribution within minoritized groups has only been reported in a few trials but appears lower than in the white population. This disparity may be attributable to the difference in the prevalence of diseases between these subgroups, as well as social and/ or cultural reasons. Nonetheless, there has been an overall increase in representation of minoritized groups over the past two decades. These observations provide important perspectives to consider when applying clinical trial learnings to clinical settings.},
}
@article {pmid39979354,
year = {2025},
author = {Abbas, Y and Hadi, HJ and Aziz, K and Ahmed, N and Akhtar, MU and Alshara, MA and Chakrabarti, P},
title = {Reinforcement-based leveraging transfer learning for multiclass optical coherence tomography images classification.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6193},
pmid = {39979354},
issn = {2045-2322},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/diagnostic imaging ; *Macular Edema/diagnostic imaging ; Diabetic Retinopathy/diagnostic imaging ; *Machine Learning ; *Image Processing, Computer-Assisted/methods ; Algorithms ; },
abstract = {The accurate diagnosis of retinal diseases, such as Diabetic Macular Edema (DME) and Age-related Macular Degeneration (AMD), is essential for preventing vision loss. Optical Coherence Tomography (OCT) imaging plays a crucial role in identifying these conditions, especially given the increasing prevalence of AMD. This study introduces a novel Reinforcement-Based Leveraging Transfer Learning (RBLTL) framework, which integrates reinforcement Q-learning with transfer learning using pre-trained models, including InceptionV3, DenseNet201, and InceptionResNetV2. The RBLTL framework dynamically optimizes hyperparameters, improving classification accuracy and generalization while mitigating overfitting. Experimental evaluations demonstrate remarkable performance, achieving testing accuracies of 98.75%, 98.90%, and 99.20% across three scenarios for multiclass OCT image classification. These results highlight the effectiveness of the RBLTL framework in categorizing OCT images for conditions like DME and AMD, establishing it as a reliable and versatile approach for automated medical image classification with significant implications for clinical diagnostics.},
}
@article {pmid39978290,
year = {2025},
author = {Al Dallal, S and El Khashab, A and Prasan, R and Safar, A and Wael, M and Abdellatif, F and Ibrahim, A},
title = {Budget Impact Analysis of Intravitreal Injections Used to Treat Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in the Dubai Healthcare System.},
journal = {Value in health regional issues},
volume = {46},
number = {},
pages = {101083},
doi = {10.1016/j.vhri.2025.101083},
pmid = {39978290},
issn = {2212-1102},
mesh = {Humans ; *Intravitreal Injections/economics/methods ; *Macular Edema/drug therapy/economics ; *Budgets/statistics &amp; numerical data ; Ranibizumab/economics/therapeutic use/administration &amp; dosage ; *Diabetic Retinopathy/drug therapy/economics ; Cost-Benefit Analysis/methods ; Recombinant Fusion Proteins/economics/therapeutic use/administration &amp; dosage ; *Macular Degeneration/drug therapy/economics ; Angiogenesis Inhibitors/economics/therapeutic use ; Antibodies, Monoclonal, Humanized/economics/therapeutic use/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor ; },
abstract = {OBJECTIVES: With the rising prevalence of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), this study assesses the budget impact of current intravitreal injections (faricimab, brolucizumab, ranibizumab, and aflibercept) on Dubai's private sector. The aim is to identify the most cost-effective intervention by evaluating utilization costs based on injection frequencies and direct acquisition expenses.<br><br>METHODS: An Excel-based budget impact model, aligned with the current standard of care, incorporates direct medical costs only, acquisition prices of the 4 interventions, procedure costs, optical coherence tomography diagnosis and consultation visit costs, and average administration costs in Dubai's healthcare system. Local experts' opinions shape the clinical approach and costs. The model spans a 5-year horizon, considering a complete replacement or gradual increase in faricimab uptake. One-way sensitivity analysis ensures outcome robustness.<br><br>RESULTS: The model, based on an estimated prevalence of 722 nAMD patients and 14 885 DME patients, projects faricimab's growing market share yielding estimated total savings of 402 908 275 Arab Emirates Dirham over 5 years compared with current market shares. The savings stem from faricimab's lower injection frequency and acquisition cost in managing DME and nAMD in Dubai's healthcare system.<br><br>CONCLUSIONS: Increasing faricimab uptake promises substantial budget savings. Decision makers in Ophthalmology Care in the United Arab Emirates can efficiently allocate resources by endorsing faricimab as the primary treatment for nAMD and DME based on these findings.},
}
@article {pmid39976962,
year = {2025},
author = {Inoda, S and Takahashi, H and Takahashi, R and Hashimoto, Y and Yoshida, H and Takahashi, H and Fujino, Y and Aizawa, K and Kawashima, H and Yanagi, Y},
title = {Effect of Combination Use of Aqueous Humor Secretion Inhibitor Eye Drops on Aflibercept Level: A Preliminary Analysis.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {2},
pages = {21},
pmid = {39976962},
issn = {2164-2591},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage ; *Aqueous Humor/metabolism/drug effects ; *Glaucoma/drug therapy/metabolism ; Intravitreal Injections ; Ophthalmic Solutions ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/pharmacokinetics/administration &amp; dosage ; Retrospective Studies ; *Wet Macular Degeneration/drug therapy/metabolism ; Case-Control Studies ; },
abstract = {PURPOSE: To investigate the association between aqueous humor (AH) suppressant eye drops and the concentration of aflibercept at 1 month after intravitreal injection.<br><br>METHODS: This retrospective study included 17 eyes of 17 patients with neovascular age-related macular degeneration (nAMD) who used eye drops for their glaucoma and received their first intravitreal aflibercept (IVA) at two centers between July 2013 and November 2020. As controls, we enrolled 40 age-, sex-, and axial length-matched eyes of 40 patients with nAMD who were not using any medication that would affect AH circulation. AH was collected 1&#xa0;month after the first IVA. Aflibercept levels were measured by enzyme-linked immunosorbent assay and were compared between controls and cases using the Kruskal-Wallis test and Dunn's test. The drugs were categorized into two groups based on their mechanism of action on the AH: outflow drugs (e.g., prostaglandin analog) and inflow drugs (e.g., carbonic anhydrase inhibitor, beta-blockers, and alpha-2 agonists).<br><br>RESULTS: Mean (interquartile range) aflibercept levels in the AH in controls and in cases who used outflow and inflow drugs were 6.83 &#xb5;g/mL (1.94-10.34), 9.93 &#xb5;g/mL (2.58-17.44), and 15.95 &#xb5;g/mL (7.20-22.57), respectively. A Kruskal-Wallis test showed a significant difference among the control, inflow, and outflow drugs (P = 0.0075). Dunn's test showed that aflibercept levels in the aqueous humor were significantly higher in cases using inflow drugs compared to both controls and cases using outflow drugs (P = 0.0085 and P = 0.044, respectively).<br><br>CONCLUSIONS: Aflibercept levels in the AH 1&#xa0;month after the first IVA were higher in cases using eye drops that reduce AH secretion than in controls.<br><br>TRANSLATIONAL RELEVANCE: Our results, together with previous studies in animals, suggest that combined use of these eye drops might extend the half-life of intravitreally injected drugs.},
}
@article {pmid39975680,
year = {2025},
author = {Charytoniuk, T and Półjanowski, S and Michalak, M and Kaźmierczak, K and Kałużny, B},
title = {The endocannabinoid system and ophthalmic pathologies: a review of molecular mechanisms and its implications for clinical practice.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1500179},
pmid = {39975680},
issn = {2296-858X},
abstract = {Within the last decade the role of the endocannabinoid system (ECS) has been a significant part of ophthalmic research, including both ocular physiology and the development of eye pathologies. It is known that this widespread cell-signaling system is involved in retinal neurobiological processes, including visual signal processing, as well as neurotransmission. Furthermore, various research indicated the involvement of ECS in the molecular basis of various pathologies, mostly glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). Therefore, the researchers believe that this biological system, its receptors, pathways, and ligands might be considered as an auxiliary compound to reduce the number of patients suffering from ophthalmic diseases. Despite presented in the literature effects of the endocannabinoid system in the eye, none of the current ECS reviews presented a comprehensive description of the endocannabinoid system, its compounds, and, subsequently ophthalmic disorders. Thus, the aim of this review was to summarize all the major data, including the most up-to-date research, concerning a correlation between the endocannabinoid system and the major ophthalmic pathologies.},
}
@article {pmid39975545,
year = {2025},
author = {Stürzbecher, L and Bartolomaeus, H and Bartolomaeus, TUP and Bolz, S and Sekulic, A and Ueffing, M and Clark, SJ and Reichhart, N and Crespo-Garcia, S and Wilck, N and Strauß, O},
title = {Outer retina micro-inflammation is driven by T cell responses prior to retinal degeneration in early age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1520188},
pmid = {39975545},
issn = {1664-3224},
mesh = {Animals ; Humans ; *Macular Degeneration/immunology/pathology ; Mice ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/immunology/pathology ; Disease Models, Animal ; *T-Lymphocytes/immunology ; CX3C Chemokine Receptor 1/genetics ; Male ; *Retina/immunology/pathology ; Female ; Inflammation/immunology/pathology ; Aged ; Geographic Atrophy/immunology/pathology ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of blindness with limited treatment options. Dysfunction of the retinal pigment epithelium (RPE) is a unifying salient feature of the pathology and a primary end-point damage leading to complications such as geographic atrophy (GA), which represents the most common end-stage of AMD.<br><br>METHODS: Human and murine ocular tissues were used for histological examinations. Furthermore, flow cytometry and gene expression analysis were used on ocular and splenic tissues of Cx3cr1 [GFP/GFP] and C57BL/6J mice at 8 and 12 months of age to characterize the dynamics of local and systemic T cell populations.<br><br>RESULTS: We show the presence of memory T cells such as CD45RO[+] cells in the choroid and retina of patients with AMD with a peak of abundance in early stages of AMD. As further evidence for the contribution of the adaptive immune system to GA we identified an increased frequency of CD44[+] CD69[+] KLRG1[+] T cells and para-inflammation of the retina in a mouse model that mimics features of GA. Importantly, the activation of T cells found at early AMD-like stages prior to degeneration possessed long-lasting cytotoxic properties and adopted typical features of senescent immune cells. T cells were intimately associated with the RPE, suggesting transmigration and participating in local micro-inflammation.<br><br>DISCUSSION: Our data support that activation and accumulation of memory T cells can be considered as a hallmark of early AMD, and that adaptive immunosenescence likely to contribute to the chronic inflammation associated with RPE damage and the progression to large lesions as seen in GA.},
}
@article {pmid39975064,
year = {2025},
author = {Nair, AP and Ghosh, S and Babu, VS and Praveen, M and Xin, Y and Sahu, GR and Vaidya, TA and Debnath, J and Raja, K and Gadde, SGK and M B, T and Shetty, N and Saxena, A and Shetty, R and Hose, S and Deshpande, V and Chakrabarty, K and Handa, JT and Qian, JJ and Sethu, S and Sinha, D and Ghosh, A},
title = {Attenuated adenosine mediated immune-dampening increases natural killer cell activity in early age-related macular degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975064},
issn = {2692-8205},
support = {K99 EY033421/EY/NEI NIH HHS/United States ; P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY031594/EY/NEI NIH HHS/United States ; R01 EY032516/EY/NEI NIH HHS/United States ; },
abstract = {Non-exudative age-related macular degeneration (AMD) involves retinal pigment epithelium (RPE) dysfunction and has been linked to altered intraocular immunity. Our investigation focuses on immune cell subsets and inflammation-associated factors in the eyes with early and intermediate AMD. We observed elevated levels of activated natural killer (NK) cells and interferon-γ, concurrent with reduced myeloid-derived suppressor cells (MDSCs) and adenosine in AMD eyes. Aqueous humor from AMD patients had diminished ability to dampen NK cell activation, an effect rescued by adenosine supplementation. The Cryba1 cKO mouse model recapitulated these immune alterations, and single-cell RNA-sequencing identified NK cell-related genes and NK cell-RPE interactions. Co-culture of activated NK cells with RPE cells induced barrier dysfunction and Gasdermin-E driven pyroptosis providing a functional link relevant to AMD. These findings suggest a double-hit model where elevated immune activation and loss of immune dampening mechanisms drive AMD progression. Resetting the intraocular immune balance may be a promising therapeutic strategy for managing early and intermediate AMD.},
}
@article {pmid39974955,
year = {2025},
author = {Singh, K and Jin, Y and Hu, MW and Palazzo, I and Cano, M and Hoang, T and Bhutto, I and Wang, S and Sinha, D and Blackshaw, S and Qian, J and Handa, JT},
title = {Cigarette smoke and biological age induce degenerative heterogeneity in retinal pigment epithelium.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39974955},
issn = {2692-8205},
support = {R01 EY035805/EY/NEI NIH HHS/United States ; R01 EY031594/EY/NEI NIH HHS/United States ; R01 EY034571/EY/NEI NIH HHS/United States ; R01 EY031779/EY/NEI NIH HHS/United States ; P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY036173/EY/NEI NIH HHS/United States ; R01 EY033765/EY/NEI NIH HHS/United States ; },
abstract = {Environmental exposure such as cigarette smoke induces epigenetic changes that can induce degenerative heterogeneity and accelerate aging. In early age-related macular degeneration (AMD), the leading worldwide cause of blindness among the elderly, retinal pigment epithelial (RPE) cell heterogeneity is a key change. Since smoking is the strongest environmental risk factor for AMD, we hypothesized that cigarette smoke induces degenerative RPE heterogeneity through epigenetic changes that are distinct from aging, and that with aging, the RPE becomes vulnerable to cigarette smoke insult. We administered cigarette smoke condensate (CSC) intravitreally to young and aged mice and performed snRNA-seq and snATAC-seq on the RPE/choroid. This analysis identified separate cell clusters corresponding to healthy and abnormal, dedifferentiated RPE in both aged vehicle-treated and young CSC-treated mice. The dedifferentiated RPE were characterized by a global decrease in chromatin accessibility and decreased expression of genes in functional categories that were linked to hallmarks of aging. Notably, young, dedifferentiated RPE also exhibited a compensatory upregulation of hallmarks of aging-related genes, specifically those related to mitochondrial function and proteostasis. In contrast, aged dedifferentiated RPE did not express these compensatory changes, and did not survive CSC treatment, as experimentally verified with TUNEL labeling. These changes are relevant to early AMD because we identified through scRNA-seq, similar dedifferentiated and healthy macular RPE clusters in a donor who smoked and another with early AMD, but not from a nonsmoker. Degenerative cellular heterogeneity can include an abnormal cluster that jeopardizes cell survival and may represent an additional hallmark of ocular aging.},
}
@article {pmid39973884,
year = {2025},
author = {Loganathan, R and Latha, S},
title = {Age-related macular degeneration diagnosis in optical coherence tomography images with gray level co-occurrence matrix features, genetic algorithms, and random forest classifier.},
journal = {Technology and health care : official journal of the European Society for Engineering and Medicine},
volume = {33},
number = {3},
pages = {1509-1521},
doi = {10.1177/09287329241301649},
pmid = {39973884},
issn = {1878-7401},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging/diagnosis ; *Algorithms ; *Image Processing, Computer-Assisted/methods ; Genetic Algorithms ; Random Forest ; },
abstract = {This paper proposes new computational strategies to improve optical coherence tomography image quality for age-related macular degeneration identification. Integrated into an age-related macular degeneration detection system, these algorithms automate and improve the identification of abnormalities in optical coherence tomography images, aiding in the classification of normal and abnormal macular tissues. The research presents an innovative approach to detecting age-related macular degeneration related anomalies, combining texture analysis, statistical evaluation, and genetic algorithms for feature selection. Genetic algorithm optimization finds the best predictive characteristics by using in-depth texture analysis with the gray level co-occurrence matrix and comprehensive statistical research. Gray level co-occurrence matrix features are analyzed at four angles (0°, 45°, 90°, and 135°), with the random forest classifier trained using optimized features. The random forest classifier plays a vital role in both the training and testing phases, achieving no-table results: an error rate of 0% for selected features, 1.9% for all features, and 7.5% for no features, and an overall system classification accuracy of 100% for training data for all, while maintaining 92.458% 98.113%, 100% for testing data of no features, all features and selected features.},
}
@article {pmid39967973,
year = {2025},
author = {Chichan, H and Aldujaly, IH and Michalakis, K and Kanal, L},
title = {Photobiomodulation in ocular therapy: current status and future perspectives.},
journal = {International journal of ophthalmology},
volume = {18},
number = {2},
pages = {351-357},
pmid = {39967973},
issn = {2222-3959},
abstract = {Photobiomodulation has been known to have potential medicinal effects for ages. It involves the use of specific wavelengths to target specific regions in the cell. Different health conditions have been reported to be treated with exposure to light such as cardiovascular conditions, inflammatory diseases, infectious diseases, and most importantly ocular diseases. This review specifically targets the treatment of retinal diseases including age-related macular degeneration, diabetic macular edema, myopia and acute retinal light injury with photobiomodulation. Red light is used in this therapy since this wavelength has lower frequency and hence minimal chance of causing any damage. Red light has the potential to penetrate cellular structures such as mitochondria and facilitate cellular processes. For ocular diseases, the target wavelength ranges between 630 to 800 nm. In most of the cases the primary target for red light is the cytochrome C oxidase enzyme in mitochondria, which alters the gene expression and promotes cellular energy production. Clinical evidence shows improvement of visual activity and reduction in thickness of retina post treatment. Future prospects of photobiomodulation involve target-specific treatment, combinational therapy to treat complex retinal diseases including gene therapy, and longitudinal studies to predict long-term efficacy and the chance of any recurrence in the patients. Hence the future of photobiomodulation holds significant potential in medicine especially in ocular diseases characterized by progress in research, technology, and clinical trials.},
}
@article {pmid39966604,
year = {2025},
author = {Hagag, AM and Holmes, C and Raza, A and Riedl, S and Anders, P and Kaye, R and Prevost, T and Fritsche, LG and Rueckert, D and Bogunović, H and Scholl, HPN and Schmidt-Erfurth, U and Lotery, AJ and Sivaprasad, S},
title = {Correction: Features of intermediate and late dry age-related macular degeneration on adaptive optics ophthalmoscopy: Pinnacle Study Report 8.},
journal = {Eye (London, England)},
volume = {39},
number = {5},
pages = {1020},
doi = {10.1038/s41433-025-03696-3},
pmid = {39966604},
issn = {1476-5454},
}
@article {pmid39963624,
year = {2025},
author = {Hirai, C and Shiraishi, E and Tsuchida, H and Shinoda, K},
title = {Development of Age-Related Macular Degeneration During Treatment for Diabetic Macular Edema: A Case Report.},
journal = {Cureus},
volume = {17},
number = {1},
pages = {e77606},
pmid = {39963624},
issn = {2168-8184},
abstract = {We report a rare case of a patient who developed age-related macular degeneration (AMD) in one eye during treatment of diabetic macular edema (DME) in both eyes. A 70-year-old man was followed for diabetic retinopathy for 23 years. At his initial visit in 200X, his decimal visual acuity was 1.0 in both eyes. He underwent panretinal photocoagulation for pre-proliferative diabetic retinopathy (PPDR) in both eyes. Optical coherence tomography (OCT), which was done nine years after the initial visit, revealed a small retinal pigment epithelial detachment (PED) in the left eye. Sixteen years after the initial visit, he developed DME in his right eye and an epiretinal membrane (ERM) in his left eye. Seventeen years after the initial visit, he developed DME in his left eye, and he was treated with sub-tenon triamcinolone acetonide (STTA) injections in the right eye. The STTA was not effective, and we switched to anti-vascular endothelial growth factor (anti-VEGF) injections for both eyes. The anti-VEGF injections were performed 22 times (aflibercept, IVA 12 times; faricimab, IVF 10 times) in the right eye for the DME. His decimal visual acuity fluctuated between 0.2 and 0.9 during this period. The left eye underwent pars plana vitrectomy (PPV) for the DME and ERM 17 years after the initial visit. Although the macular edema was resolved, subretinal fluid and macular neovascularization (MNV) appeared 22 years after the initial visit. Since then, IVF has been performed 10 times, and the decimal visual acuity has improved from 0.4 to 0.8. He underwent bilateral cataract surgery 17 years after the initial visit. Twenty-two years after the initial visit, the left eye developed MNV, located near the PED that had been seen on the OCT image taken 13 years earlier. The relationships of the ERM, DME, and PPV with MNV were not determined. At present, both eyes are responding well to the IVF treatments. This case will remind clinicians of the possibility of the two diseases coexisting and will lead to a better understanding of the pathogenic mechanisms of both diseases.},
}
@article {pmid39963552,
year = {2025},
author = {Nagai, N and Matsubara, H and Terasaki, H and Hirano, T and Kato, A and Miki, A and Hirai, H and Murao, F and Imaizumi, H and Gomi, F and Mitamura, Y and Ogata, N and Kusuhara, S and Yasukawa, T and Murata, T and Sakamoto, T and Kondo, M and Shinoda, H and Ozawa, Y},
title = {Extent of Complete Retinal Pigment Epithelial and Outer Retinal Atrophy with Foveal Center Involvement is Associated with Visual Acuity.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100612},
pmid = {39963552},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the OCT images of eyes with fovea-involved complete retinal pigment epithelial and outer retinal atrophy (cRORA) as well as best-corrected visual acuity (BCVA) to explore the pathogenesis of visual impairment and atrophy.<br><br>DESIGN: Retrospective observational study.<br><br>SUBJECTS: Data of eyes with cRORA associated with age-related macular degeneration with foveal center involvement were collected from 10 hospitals in Japan.<br><br>METHODS: Ophthalmic examination data, BCVA, and extents of retinal pigment epithelial and outer retinal atrophy (RORA), represented by choroidal hyper-transmission, and outer plexiform layer (OPL) deterioration, central retinal thickness (CRT), and central choroidal thickness (CCT) measured using built-in software on the sectional OCT images were evaluated.<br><br>MAIN OUTCOME MEASURES: Relationship between BCVA and extents of RORA and OPL deterioration.<br><br>RESULTS: Of the 64 eyes of 64 patients (mean age: 76.8&#xa0;&#xb1;&#xa0;9.5 years old), 38 eyes (59.4%) belonged to men. Mean BCVA was 0.602&#xa0;&#xb1;&#xa0;0.475 (median: 0.523; range,&#xa0;-0.079 to 1.523) in logarithm of the minimum angle of resolution (logMAR). Mean extent of RORA was 2921&#xa0;&#xb1;&#xa0;1291 (median: 3172; range: 479-5985) &#x3bc;m. BCVA in logMAR positively correlated with extents of RORA (P&#xa0;=&#xa0;0.004) and OPL deterioration (P&#xa0;=&#xa0;0.004) and negatively correlated with CRT (P&#xa0;=&#xa0;0.022). Best-corrected visual acuity &#x2265;0.5 was associated with extents of RORA &#x2265;3000 &#x3bc;m (odds ratio [OR], 4.227; 95% confidence interval [CI], 1.440-12.408; P&#xa0;=&#xa0;0.009) and OPL deterioration &#x2265;1700 &#x3bc;m (OR, 2.984; 95% CI, 1.034-8.609; P&#xa0;=&#xa0;0.043), and presence of complete central outer plexiform layer defect (cCOD) (OR, 12.700; 95% CI, 2.439-66.132; P&#xa0;=&#xa0;0.003), after adjusting for age and sex. The extent of RORA &#x2265;3000 &#x3bc;m was associated with BCVA &#x2265;0.5 (OR, 4.213; 95% CI, 1.437-12.356; P&#xa0;=&#xa0;0.009), extent of OPL deterioration &#x2265;1700 &#x3bc;m (OR, 58.682; 95% CI, 6.865-501.592; P&#xa0;<&#xa0;0.001), and presence of cCOD (OR, 4.107; 95% CI, 1.339-12.604; P&#xa0;=&#xa0;0.014), after adjusting for age and sex. The extent of RORA positively correlated with that of OPL deterioration (P&#xa0;<&#xa0;0.001), CRT (P&#xa0;=&#xa0;0.001), and CCT (P&#xa0;=&#xa0;0.041).<br><br>CONCLUSIONS: A longer extent of cRORA in the OCT images with foveal center involvement was associated with a longer extent of OPL deterioration and the presence of cCOD and worse BCVA. Further studies focusing on OPL changes are warranted for understanding the pathogenesis of RORA and vision loss.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39962357,
year = {2025},
author = {Oh, Y and Song, SJ},
title = {Association of Steatotic Liver Disease with Retinal Vascular Occlusion: The Influence of Obesity in a Large Health Screening Cohort.},
journal = {Endocrinology and metabolism (Seoul, Korea)},
volume = {40},
number = {2},
pages = {299-303},
pmid = {39962357},
issn = {2093-5978},
mesh = {Humans ; Male ; Female ; Middle Aged ; Cross-Sectional Studies ; *Obesity/complications/epidemiology ; *Retinal Vein Occlusion/epidemiology/etiology ; Risk Factors ; Adult ; *Fatty Liver/complications/epidemiology ; Aged ; Cohort Studies ; Mass Screening ; Body Mass Index ; *Non-alcoholic Fatty Liver Disease/complications/epidemiology ; Follow-Up Studies ; Prognosis ; },
abstract = {In this cross-sectional study, we aimed to investigate the relationship between steatotic liver disease (SLD) and retinal abnormalities in a cohort undergoing health screening. Our study included 353,607 participants who underwent fundus photography and abdominal ultrasonography at least once at the Kangbuk Samsung Health Promotion Center from 2002 to 2022. After adjusting for age and sex, the risk of retinal vein occlusion (RVO) significantly increased with the presence of non-alcoholic fatty liver disease, metabolic dysfunction-associated fatty liver disease, and metabolic dysfunction-associated SLD, with odds ratios of 1.259 (95% confidence interval [CI], 1.050 to 1.510), 1.498 (95% CI, 1.249 to 1.796), and 1.342 (95% CI, 1.121 to 1.605), respectively. However, these associations weakened after adjusting for body mass index. No statistically significant associations were observed with other retinal disorders after adjusting for age, sex, and other confounding factors. Our findings suggest that obesity may mediate the relationship between SLD and RVO, while other retinal abnormalities may be more closely associated with known risk factors rather than SLD itself.},
}
@article {pmid39962248,
year = {2025},
author = {Honda, S and Maruyama-Inoue, M and Otsuji, T and Kyo, A and Kobayashi, Y and Yamamoto, Y and Gomi, F},
title = {Efficacy and safety of brolucizumab every 6 weeks induction therapy for neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {5705},
pmid = {39962248},
issn = {2045-2322},
support = {22 K09773//Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT)/ ; },
mesh = {Humans ; Male ; Female ; Aged ; Retrospective Studies ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects/therapeutic use ; Visual Acuity/drug effects ; Treatment Outcome ; Aged, 80 and over ; *Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects/therapeutic use ; Intravitreal Injections ; Middle Aged ; },
abstract = {This retrospective study aims to evaluate the short-term efficacy and safety of brolucizumab every 6 weeks induction therapy for neovascular age-related macular degeneration (nAMD) cases. This study included 140 eyes from 140 patients (101 males and 39 females, with a mean age of 77.7 ± 8.7 years) with nAMD who received brolucizumab injections every 6 weeks as part of induction therapy across four participating centers between June 2020 and March 2024. Follow-up lasted for at least 20-24 weeks. Data collected included age, sex, history of nAMD treatment, best-corrected visual acuity (BCVA), central retinal thickness (CRT), presence or absence of exudation, and occurrence of intraocular inflammation (IOI). Sixty-one eyes had prior nAMD treatment. Mean BCVA (logMAR) was 0.40 ± 0.43 before brolucizumab therapy, improving to 0.38 ± 0.42, 0.33 ± 0.41, and 0.34 ± 0.44 after the first, second, and third injections, respectively. Significant improvements in BCVA were observed from the second injection onward (p < 0.05). CRT decreased significantly from baseline of 341.6 ± 151.0 to 219.1 ± 119.8, 204.0 ± 112.9, and 200.8 ± 96.0 after the first, second, and third injections, respectively (p < 1.0 × 10[-20]). Exudative findings, present in all cases before treatment, resolved in 64.3%, 82.1%, and 79.3% of cases after the first, second, and third injections, respectively. IOI was observed in five, three, and four eyes after the first, second, and third injections, respectively, accounting for 8.6% of all cases. No cases had retinal vasculitis or occlusion. In conclusion, brolucizumab administered every 6 weeks as induction therapy for nAMD showed favorable efficacy and safety outcomes during a 6-month follow-up.},
}
@article {pmid39962207,
year = {2025},
author = {Zhou, Y and Jia, W and Song, J and Li, M and Dai, W and Zou, J and Zhou, J and Chen, X and Li, X},
title = {Burdens and trends of age-related macular degeneration at global, regional, and national levels,1990-2021: findings from the 2021 global burden of disease study.},
journal = {Eye (London, England)},
volume = {39},
number = {8},
pages = {1517-1525},
pmid = {39962207},
issn = {1476-5454},
support = {XK-073-3//Zhongshan Hospital/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology ; Global Burden of Disease/trends ; Male ; Female ; Aged ; Prevalence ; Global Health/statistics &amp; numerical data ; Middle Aged ; Aged, 80 and over ; Age Distribution ; Disability-Adjusted Life Years ; Cost of Illness ; Sex Distribution ; },
abstract = {OBJECTIVES: To assess global, regional, and national burdens and trends of age-related macular degeneration (AMD) from 1990 to 2021.<br><br>METHODS: Data from the Global Burden of disease Study 2021(GBD 2021) were used. The primary measurement were prevalent cases, years lived with disability (YLDs), age-standardised prevalence rate (ASPR) and age-standardised YLDs rate (ASYR), categorized by age and sociodemographic index (SDI). Trend analysis was measured by calculating average annual percentage change (AAPC) of ASPR and ASYR.<br><br>RESULTS: Globally, the prevalent AMD cases increased to 8,057,520.459 (95% uncertainty interval [UI], 6,705,283.83 to 9,823,237.34) in 2021, with associated YLDs rising to 577,984.5004 (95% UI, 401,188.20 to 797,657.63). AMD burdens varied across regions and countries, as well as level of SDI development. China, India, and the United States of America (USA) were the top three countries with AMD cases. Caribbean regions have significant lower ASPR and ASYR of AMD. The AMD burden peaked between ages 65-69. Females had a significantly higher burden of AMD compared to males. From 1990 to 2021, the global ASPR and ASYR showed downward trend (AAPC&#x2009;=&#x2009;-0.15, 95% confidence interval [CI], -0.19 to -0.12, P&#x2009;<&#x2009;0.001; AAPC&#x2009;=&#x2009;-0.69, 95% CI, -0.71 to -0.67, P&#x2009;<&#x2009;0.001) respectively. The USA is the only developed country showed decreasing AAPCs of ASPR and ASYR from 1990 to 2021 but increasing AAPCs of ASPR and ASYR from 2012 to 2021.<br><br>CONCLUSIONS: AMD burdens increased over 30 years, varying by age, sex, and SDI, guiding global strategies and public health interventions.},
}
@article {pmid39962206,
year = {2025},
author = {Tang, F and Hogg, RE and Higgins, BE and Wright, DM and Smyth, L and Sivaprasad, S},
title = {Polygenic Risk Score Impact on Visual Function in Older Individuals with Healthy Macula: The Northern Ireland Sensory Ageing Study.},
journal = {Eye (London, England)},
volume = {39},
number = {8},
pages = {1508-1516},
pmid = {39962206},
issn = {1476-5454},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Macular Degeneration/genetics/physiopathology ; Northern Ireland/epidemiology ; *Visual Acuity/physiology ; *Macula Lutea/physiology ; Aged, 80 and over ; *Multifactorial Inheritance ; Risk Factors ; Polymorphism, Single Nucleotide ; Visual Fields/physiology ; ROC Curve ; *Aging/physiology ; Genetic Risk Score ; },
abstract = {BACKGROUND/OBJECTIVES: Although polygenic risk scores (PRSs) have been developed for age-related macular degeneration (AMD), it is not known whether these scores are associated with impairment of visual functions in older individuals with healthy macula. We evaluated age-related changes in visual function in people aged 55 years or above with healthy macula and determined the associations of age-related visual function changes with AMD PRS in people with healthy macula.<br><br>SUBJECTS/METHODS: Participants aged 55 years or above with healthy macula and a comparative group of people with early or intermediate AMD from the Northern Ireland Sensory Ageing study were included. 45 SNPs were included for PRS calculation.<br><br>RESULTS: A total of 470 participants with healthy macula were included (Beckman grade 0 or 1). The comparator group consisted of participants with early AMD (n&#x2009;=&#x2009;87) or intermediate AMD (n&#x2009;=&#x2009;48). All visual functions except metrics of central visual field assessment showed a significant decline with age in adjusted linear regression models. Rod intercept time (RIT) was the only visual function significantly associated with PRS with Beta&#x2009;=&#x2009;0.12 (95% confidence interval: 0.01-0.23), P&#x2009;=&#x2009;0.03. A PRS integrated model achieved the highest area under the receiver operating characteristic curve (AUC) of 0.803 (0.732&#xa0;to&#xa0;0.874) to distinguish between normal or increased RIT.<br><br>CONCLUSIONS AND RELEVANCE: We observed a significant decline in multiple visual functions with increasing age. However, PRS was significantly associated with RIT only, highlighting the genetic association of age-related decline in rod function.},
}
@article {pmid39961901,
year = {2025},
author = {Mohtashami, Z and Schneider, K and Azimi, R and Atilano, S and Chwa, M and Kenney, MC and Singh, MK},
title = {Exploring the therapeutic potential of MOTS-c in age-related macular degeneration: from cellular responses to patient-derived cybrids.},
journal = {Human cell},
volume = {38},
number = {2},
pages = {57},
pmid = {39961901},
issn = {1749-0774},
support = {EY027363//NEI R01/ ; },
mesh = {Humans ; *Macular Degeneration/drug therapy/genetics/pathology ; Apoptosis/drug effects/genetics ; *Retinal Pigment Epithelium/cytology/pathology/drug effects ; Cell Survival/drug effects ; Mitochondria/metabolism ; Organelle Biogenesis ; Gene Expression/drug effects ; Cell Line ; Cells, Cultured ; Cell Differentiation/drug effects ; Dose-Response Relationship, Drug ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of irreversible vision loss in the US, is on the rise among the elderly. Uncontrolled mitochondria-derived peptide production from mtDNA disruption and 16S or 12S rRNA damage could worsen AMD. Our previous work has shown that Humanin G possesses cytoprotective effects in retinal pigment epithelial (RPE) cells. However, MOTS-c, a highly efficient mitochondrial peptide, has yet to be evaluated on retinal cell survival. In this study, we show that there are differences in effects between wild-type (wt-) and differentiated ARPE19 cells (diff-ARPE19), implying that the cellular differentiation status may influence how cells respond to MOTS-c. MOTS-c has dose-dependent effects on apoptosis, inflammation, and mitochondrial biogenesis in diff-ARPE19 cells. Lower doses (500 nM) have more significant impacts than 5 µM concentrations. In diff-ARPE19 cells, a lower dose of MOTS-c can reduce the negative impact of hypoxia on cellular survival and gene expression, including apoptosis (CASP3, CASP9), mitochondrial biogenesis (TFAM, PGC-1α), and metabolic sensor (AMPK). However, it had no significant effect on ROS levels or NRF1 expression, regardless of MOTS-c dose. Exposing diff-ARPE19 cells to varied MOTS-c dosages before and after therapy in a chemically induced hypoxic environment yields no extra benefits as compared to MOTS-c treatment alone. MOTS-c had different effects on the expression of genes linked with apoptosis, mitochondrial biogenesis, and antioxidant activity in AMD patients versus age-matched control cybrids. The MOTS-c peptide appears to enhance cellular metabolism and regulate gene expression, which could potentially provide therapeutic benefits in AMD.},
}
@article {pmid39961453,
year = {2025},
author = {Ruddin, G and McCann, T and Fehilly, JD and Kearney, J and Kennedy, BN},
title = {The dark and bright sides of retinal G protein-coupled receptor (RGR) in vision and disease.},
journal = {Progress in retinal and eye research},
volume = {106},
number = {},
pages = {101339},
doi = {10.1016/j.preteyeres.2025.101339},
pmid = {39961453},
issn = {1873-1635},
mesh = {Humans ; *Receptors, G-Protein-Coupled/physiology/metabolism ; Animals ; *Vision, Ocular/physiology ; *Retinal Pigment Epithelium/metabolism ; *Retinal Degeneration/metabolism/physiopathology ; *Retinal Diseases/metabolism ; Macular Degeneration/metabolism ; Eye Proteins ; },
abstract = {The visual chromophore 11-cis-retinal (11cRAL) is essential to vertebrate phototransduction and therefore, must be regenerated so vision can be sustained. 11cRAL regeneration mediated by the classical visual cycle is insufficient under photopic conditions. Expressed in the retinal pigment epithelium (RPE) and Müller glia, the retinal G protein-coupled receptor (RGR) can act as an alternative visual cycle photoisomerase, photogenerating 11cRAL in bright light conditions. While named a G protein-coupled receptor, RGR has no known coupled G protein. In the photoisomerase process, RGR bound all-trans-retinal (atRAL) is converted to 11cRAL. Here, we review how this core reaction integrates into RPE and Müller cell visual cycles. Significantly, mutations in human RGR are associated with inherited retinal degeneration and age-related macular degeneration, ocular diseases impairing vision. In this article, we comprehensively review 30 years of research into this membrane-bound protein, to comprehend RGR's i) biological role in vision, ii) association with ocular disease, iii) and surprising role in non-ocular function and disease. We discuss studies with opposing views on the proposed role of RGR as mediating a non-canonical visual cycle which photogenerates 11cRAL. We highlight knowledge gaps that current RGR research is addressing.},
}
@article {pmid39961437,
year = {2025},
author = {Cui, Y and Poudel, S and Xu, N and Zhou, K and Cheng, R and Liang, W and Yuan, T and Zhao, L and Qin, C and Stevens, KG and Duerfeldt, AS and Hu, J and Xu, Q and Ma, JX},
title = {Sustained release of a novel non-fibrate PPARα agonist from microparticles for neuroprotection in murine models of age-related macular degeneration.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {380},
number = {},
pages = {910-926},
doi = {10.1016/j.jconrel.2025.02.037},
pmid = {39961437},
issn = {1873-4995},
support = {R01 EY035519/EY/NEI NIH HHS/United States ; R01 EY032930/EY/NEI NIH HHS/United States ; R01 EY033477/EY/NEI NIH HHS/United States ; R01 EY034510/EY/NEI NIH HHS/United States ; R01 EY028949/EY/NEI NIH HHS/United States ; R01 EY019309/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *PPAR alpha/agonists ; Delayed-Action Preparations/administration &amp; dosage ; Disease Models, Animal ; *Neuroprotective Agents/administration &amp; dosage/therapeutic use ; Mice, Inbred C57BL ; Mice ; Mice, Knockout ; Male ; *Macular Degeneration/drug therapy/pathology/metabolism ; Retina/drug effects/metabolism/pathology ; Receptors, LDL/genetics ; },
abstract = {Prior research has demonstrated the therapeutic potential of peroxisome proliferator-activated receptor α (PPARα) agonist fenofibrate on diabetic retinopathy. In the present study, a novel non-fibrate PPARα agonist, A190, was designed with higher potency and selectivity than fenofibrate in PPARα agonism. A190 was encapsulated in biodegradable microparticles (A190-MP) to ensure sustained drug release, with detection in the retina up to 6 months following a single intravitreal injection. A190-MP alleviated retinal dysfunction as shown by electroretinography in Vldlr[-/-] (wet-AMD model) and Abca4[-/-]/Rdh8[-/-] (dry-AMD model) mice. A190-MP also attenuated the decreases in cone photoreceptor density and outer nuclear layer thickness as demonstrated by optical coherence tomography and histology. Moreover, A190-MP reduced vascular leakage and neovascularization in Vldlr[-/-] mice, suggesting an anti-inflammatory and anti-angiogenic effect. A190-MP upregulated expression of PPARα, PGC1α, and TOMM20 in the retina of Vldlr[-/-] and Abca4[-/-]/Rdh8[-/-] mice. A190-MP also improved retinal mitochondrial function as shown by Seahorse analysis using retinal biopsy. In vitro, A190 attenuated oxidative stress and preserved cell viability in a photoreceptor-derived cell line exposed to 4-HNE and improved mitochondrial function, via a PPARα-dependent mechanism. These findings revealed sustained therapeutic effects of A190-MP in wet and dry AMD models, through improving mitochondrial function by activating PPARα.},
}
@article {pmid39960315,
year = {2025},
author = {Choi, H and Corradetti, G and Lindenberg, S and Karamat, AN and Oncel, D and Liu, H and Gnanaraj, R and Fasih-Ahmad, S and Marion, KM and Baker, KL and Gulati, S and Foster, B and Lam, A and Sadda, SR and Lally, DR},
title = {Incomplete RPE and Outer Retinal Atrophy (iRORA) Development in Eyes With Fellow-eye Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {5},
pages = {274-279},
doi = {10.3928/23258160-20250108-01},
pmid = {39960315},
issn = {2325-8179},
mesh = {Humans ; Female ; Male ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology ; Aged ; Atrophy ; Aged, 80 and over ; *Wet Macular Degeneration/diagnosis/complications ; Retrospective Studies ; Follow-Up Studies ; Fluorescein Angiography/methods ; Visual Acuity ; Fundus Oculi ; },
abstract = {BACKGROUND AND OBJECTIVE: The utility of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) in intermediate age-related macular degeneration (iAMD) as a clinical endpoint is not yet elucidated. We aim to understand the time to iRORA development in iAMD.<br><br>PATIENTS AND METHODS: Eyes with iAMD without iRORA of subjects with fellow-eye neovascular AMD (nAMD) were identified from visits between 2010 and 2019 at a tertiary clinic. Spectral Domain Optical Coherence Tomography 512 &#xd7; 128mm macular cubes (Cirrus HD-OCT, Zeiss) were assessed for time to first detection of iRORA and complete RPE and Outer retinal atrophy (cRORA) at 24 months. Up to three iRORA lesions were followed. Univariable Cox regressions evaluated baseline OCT characteristics, age, and gender as predictors for iRORA or cRORA development. Baseline OCT characteristics included intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits (SDD), hyporeflective drusen cores (hDC), and drusen volume measured with semi-automatic segmentation of Bruch's membrane to RPE.<br><br>RESULTS: In 101 eyes of 101 subjects (64% female; median 81 years old), 28.70% (n = 30) developed iRORA whereas 2.97% (n = 3) developed cRORA without iRORA at 24 months. Median (range) time to first iRORA or cRORA was 20 (12 to 24) months. The presence of baseline IHRF was associated with increased risk of iRORA development at month 24 (HR = 2.28, 95% CI: 1.14 to 4.56; P value = 0.019).<br><br>CONCLUSION: In subjects with fellow-eye nAMD, approximately one third of iAMD eyes developed iRORA at 24 months. Intraretinal hyperreflective foci was associated with a two-fold increased risk in iRORA development. [Ophthalmic Surg Lasers Imaging Retina 2025;56:274-279.].},
}
@article {pmid39959882,
year = {2025},
author = {Ruamviboonsuk, V and Kongwattananon, W and Chuaypen, N},
title = {Changes in Aqueous Humor Cytokine Profile Following Intravitreal Brolucizumab Injection.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {427-437},
pmid = {39959882},
issn = {1177-5467},
abstract = {PURPOSE: Intravitreal brolucizumab, approved for neovascular age-related macular degeneration (nAMD), may trigger immune responses leading to intraocular inflammation (IOI) by increasing pro-inflammatory cytokines. This study evaluates cytokine levels in the aqueous humor of patients before and after intravitreal brolucizumab injection.<br><br>PATIENTS AND METHODS: Fourteen eyes of fourteen participants with nAMD or polypoidal choroidal vasculopathy (PCV) and who received intravitreal brolucizumab injection were included. Aqueous humor was collected before and 1 month following the injection. The aqueous cytokine profile was analyzed using a bead-based multiplex immunoassay. Paired t-test and Wilcoxon-signed rank test were used to analyze the results.<br><br>RESULTS: Ten eyes were diagnosed with PCV, and four were nAMD. The aqueous IL-8 and IL-22 levels were significantly increased after intravitreal brolucizumab injection with a mean change of 18.2 &#xb1; 32.57 pg/mL (95% CI -0.61 to 37.01, p = 0.04) and 15.46 &#xb1; 24.14 pg/mL (95% CI 1.53-29.40, p = 0.03), respectively. VEGF-A was significantly decreased with a mean change of -915.4 &#xb1; 831.72 pg/mL (95% CI -1395.62 to -435.18, p < 0.01). One patient was diagnosed with IOI, and the cytokine profile showed increased in aqueous pro-inflammatory cytokines (Exotaxin, G-CSF, IL-8, IL-10, IL-22, IL-10, MCP-1 and TNF- &#x3b1;) and decreased in VEGF-A level compared with baseline.<br><br>CONCLUSION: Our study demonstrated a significant increase in aqueous pro-inflammatory cytokines in eyes treated with intravitreal brolucizumab. Nearly all eyes studied showed no clinical signs of intraocular inflammation. The results suggested that type IV cell-mediated hypersensitivity could play a role in IOI following intravitreal brolucizumab injection.},
}
@article {pmid39959178,
year = {2024},
author = {Yadav, A and Phogat, J and Yadav, M and Bhardwaj, A and Yadav, R and Nada, M and Bhati, M and Goel, S and Thakur, R and Kumar, R and Singh, M and Tanwar, M},
title = {Analysis of interleukin-6 gene polymorphism and its serum levels in Indian age-related macular degeneration patients.},
journal = {Molecular vision},
volume = {30},
number = {},
pages = {434-446},
pmid = {39959178},
issn = {1090-0535},
mesh = {Humans ; *Interleukin-6/genetics/blood ; *Polymorphism, Single Nucleotide ; Male ; Female ; Case-Control Studies ; India ; Aged ; *Macular Degeneration/genetics/blood ; Middle Aged ; Gene Frequency ; Genetic Predisposition to Disease ; Aged, 80 and over ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a complex condition involving multiple factors. The condition is associated with numerous inflammatory indicators, including cytokines. Single-nucleotide polymorphisms in cytokine genes can also modify gene expression, perhaps contributing to the development of the disease. The objective of the present study was to examine the correlation among IL-6 SNPs (rs1800795, rs1800796, and rs1800797) and the serum levels of IL-6 in AMD patients treated at the Regional Institute of Ophthalmology of Pt. B.D. Sharma PGIMS, Rohtak (Haryana), India.<br><br>METHODS: This case-control study included 131 patients diagnosed with AMD using precise ophthalmic examinations, such as&#xa0;slit lamp examination, fundoscopy, and ocular coherence tomography. To provide a basis for comparison, we also enlisted 100 healthy individuals as controls. Serum IL-6 protein levels were measured in both patients and controls using an enzyme-linked immunosorbent assay kit (ELISA). Genotyping IL-6 SNPs was performed using the PCR and DNA Sanger sequencing technique.<br><br>RESULTS: IL-6 serum levels were considerably elevated in individuals with AMD compared to the control group (p < 0.05). Statistically significant differences were seen in the genotype frequencies of rs1800795 (p = 0.027) and rs1800797 (p = 0.0011) among the AMD&#xa0;patients and the healthy controls. Furthermore, strong correlations were observed between rs1800795 and the likelihood of developing AMD based on the heterozygous (OR = 2.04; p = 0.025), dominant (OR = 1.80; p = 0.035), and over-dominant models (OR = 2.10; p = 0.0094). Additionally, there were notable associations between rs1800797 and vulnerability to AMD through heterozygous (OR = 3.21; p = 0.009), dominant (OR = 2.74; p = 0.004), and over-dominant (OR = 3.11; p = 0.002) models. The rs1800795, rs1800796, and rs1800797 haplotypes C-G-A and G-G-A were linked to an elevated risk of AMD (p = 0.005, p = 0.024. respectively).<br><br>CONCLUSIONS: Our findings indicated a significant elevation in IL-6 serum levels among the AMD patient group compared to the control group. The interleukin-6 gene polymorphisms rs1800795 and rs1800797 were linked to an elevated risk of AMD in our study population.},
}
@article {pmid39959171,
year = {2024},
author = {Altankhuyag, A and Ganbold, C and Byambadorj, B and Tumurbaatar, S and Sodnomtseren, P and Davaatseren, U and Jav, S},
title = {The interactions between ARMS2, CFH, VEGF-A and environmental factors on the risk of age-related macular degeneration.},
journal = {Molecular vision},
volume = {30},
number = {},
pages = {320-335},
pmid = {39959171},
issn = {1090-0535},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/genetics ; *Macular Degeneration/genetics/etiology/epidemiology ; *Complement Factor H/genetics ; Male ; Female ; Aged ; Polymorphism, Single Nucleotide ; Case-Control Studies ; Risk Factors ; Genetic Predisposition to Disease ; *Proteins/genetics ; Middle Aged ; Gene Frequency ; Alleles ; *Gene-Environment Interaction ; Genotype ; Aged, 80 and over ; Polymorphism, Restriction Fragment Length ; },
abstract = {BACKGROUND: Age related macular degeneration (AMD) is a multifactorial disease caused by a combination of environmental and genetic factors. The prevalence of allele and genotypeof AMD-related genes is varied throughout the world due to racial and ethnic differences. Number of previous studies have shown that the polymorphisms in the ARMS2, CFH and VEGF-A genes are associated with AMD. In Mongolia, there is a lack of sufficient data on AMD development in its population and thus needs more studies on the topic. Therefore, it needs more studies about AMD development in the population. For this reason, we have investigated several specified polymorphisms in CFH, VEGF-A and ARMS2 genes to reveal a relationship with AMD and determine the prevalence of alleles and genotypes of the genes in Mongolian population.<br><br>METHODS: Totally 161 AMD patients and 223 controls were enrolled in this case-control study. The polymorphisms in CFH, ARMS2 and VEGF-A were detected by using the methods of allele-specific polymerase chain reaction (ASPCR) and PCR based restriction fragment length polymorphism (RFLP). Statistical analysis were performed by STATA 13.0, SNPAlyze 9.0 and MDR 3.0.2.<br><br>RESULTS: According to the study result, the characteristics of hypertension, constant-wearing sunglasses and anticoagulant medications in AMD group were significantly different from those in the control group. As for the dominant model, T allele of ARMS2 rs10490924 (cOR=4.45; 95% CI, 2.44-8.13, p<0.001, aOR=5.08; 95% CI, 2.70-9.59, p<0.001) was more frequent among patients with AMD in comparison with the control group. Also, G/G genotype of CFH rs800292 (cOR=11.61; 95% CI, 3.41-39.51, p<0.001, aOR=12.49; 95% CI, 3.47-44.91, p<0.001) and G/G genotype of CFH rs1065489 (cOR=4.19; 95% CI, 2.53-6.93, p<0.001, aOR=4.67; 95% CI, 2.71-8.05, p<0.001) were significantly higher in AMD group after Bonferroni correction. This result suggests that people who carrying the risk genotypes of these polymorphisms had an increased risk for AMD development. As for the models of three or more SNP interactions, the participants with any combinations of risk genotypes have 6 to 106-fold higher risk for AMD development. This result suggests that there is some positive-additive interaction existing between the genetic variants of ARMS2, CFH and VEGF-A genes for AMD development. Our study also revealed that the participants with hypertension and carrying G/G for rs1065489 in CFH gene or non G/G for rs10490924 in ARMS2 gene genotypes had 9 to 14 times higher risk for AMD development (cOR=9.05; 95% CI, 4.38-18.68, p<0.001, RERI=4.546; AP=0.502, S=2.298, cOR=13.98; 95% CI, 3.19-61.1, p<0.001, RERI=5.85; AP=0.419, S=1.821) with high level of significance. Moreover, it was found that the participants who avoided wearing sunglasses and had the G/G genotype of ARMS2 rs10490924 or G/G genotype of CFH rs800292 had an extremely higher risk for AMD development (p<.001).<br><br>CONCLUSIONS: In conclusion, it was observed that the combination of SNPs in ARMS2, CFH and VEGF-A genes increase the risk for AMD with 6 to 106-fold. Moreover, we found that the participants with hypertension and carrying the non G/G genotype of ARMS2 rs10490924 or the G/G genotype of CFH rs800292 had an extremely higher risk of AMD development.},
}
@article {pmid39957594,
year = {2025},
author = {Wang, H and Zhang, L and Bai, X and Wang, H and Sun, H},
title = {Propofol Protects against Pyroptosis of Photoreceptors in Subretinal Hemorrhage via Regulating SIRT6/NLRP3 Signaling.},
journal = {Critical reviews in eukaryotic gene expression},
volume = {35},
number = {2},
pages = {75-85},
doi = {10.1615/CritRevEukaryotGeneExpr.2024056605},
pmid = {39957594},
issn = {2162-6502},
mesh = {*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Propofol/pharmacology ; *Pyroptosis/drug effects ; *Sirtuins/metabolism/genetics ; Signal Transduction/drug effects ; Animals ; *Retinal Hemorrhage/metabolism/drug therapy/pathology ; Humans ; Mice ; *Photoreceptor Cells/drug effects/metabolism ; Macular Degeneration/metabolism ; },
abstract = {Subretinal hemorrhage-induced neurotoxicity is a key cause of vision loss in age-related macular degeneration (AMD). The purpose of this study is to investigate the effects of Propofol on neurotoxicity. Oxygen glucose deprivation (OGD) was used to establish in vitro subretinal hemorrhage model. Gene expression was determined using reverse transcription-quantitative polymerase chain reaction and western blot. Cytokine release was determined using enzyme-linked immunosorbent assay. The interaction between sirtuin 6 (SIRT6) and NLR family pyrin domain containing 3 (NLRP3) was detected using co-immunoprecipitation assay. Cellular function was determined using cell counting kit-8 assay, lactate dehydrogenase assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Propofol suppressed the inflammatory response induced by OGD. Moreover, Propofol inhibited the neurotoxicity and pyroptosis of photoreceptors. Propofol mediated the overexpression of SIRT6, which was downregulated in AMD. Inhibition of SIRT6 alleviated its deacetylation of NLRP3. Additionally, SIRT6 deficiency antagonized the effects of Propofol and promoted the neurotoxicity and pyroptosis of photoreceptors. Taken together, Propofol protects against subretinal hemorrhage-induced neurotoxicity and pyroptosis of photoreceptors via promoting SIRT6-mediated deacetylation of NLRP3.},
}
@article {pmid39957408,
year = {2025},
author = {Chowdhury, O and Bammidi, S and Gautam, P and Babu, VS and Liu, H and Shang, P and Xin, Y and Mahally, E and Nemani, M and Koontz, V and Lathrop, K and Kedziora, KM and Franks, J and Sun, M and Smith, JW and DeVine, LR and Cole, RN and Stepicheva, N and Strizhakova, A and Chattopadhyay, S and Hose, S and Zigler, JS and Sahel, JA and Qian, J and Guha, P and Handa, JT and Ghosh, S and Sinha, D},
title = {Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice.},
journal = {Aging cell},
volume = {24},
number = {6},
pages = {e70018},
pmid = {39957408},
issn = {1474-9726},
support = {//University of Pittsburgh School of Medicine Jennifer Salvitti Davis, MD. Chair Professorship Start-up funding/ ; R01 EY031594/EY/NEI NIH HHS/United States ; R01EY031594/EY/NEI NIH HHS/United States ; K99 EY033421/EY/NEI NIH HHS/United States ; //Research to Prevent Blindness Unrestricted funds to Pitt Dept of Ophthalmology/ ; R01 EY032516/EY/NEI NIH HHS/United States ; K99EY033421/EY/NEI NIH HHS/United States ; P30EY08098/EY/NEI NIH HHS/United States ; P30 EY008098/EY/NEI NIH HHS/United States ; R01EY032516/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *TOR Serine-Threonine Kinases/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; *Macular Degeneration/pathology/metabolism/genetics ; *Epithelial-Mesenchymal Transition ; *Autophagy ; *Signal Transduction ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Humans ; Mice, Inbred C57BL ; },
abstract = {The mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/2) are crucial for various physiological functions. Although the role of mTORC1 in retinal pigmented epithelium (RPE) homeostasis and age-related macular degeneration (AMD) pathogenesis is established, the function of mTORC2 remains unclear. We investigated both complexes in RPE health and disease. Therefore, in this study, we have attempted to demonstrate that the specific overexpression of mammalian lethal with Sec13 protein 8 (mLST8) in the mouse RPE activates both mTORC1 and mTORC2, inducing epithelial-mesenchymal transition (EMT)-like changes and subretinal/RPE deposits resembling early AMD-like pathogenesis. Aging in these mice leads to RPE degeneration, causing retinal damage, impaired debris clearance, and metabolic and mitochondrial dysfunction. Inhibition of mTOR with TORIN1 in vitro or βA3/A1-crystallin in vivo normalized mTORC1/2 activity and restored function, revealing a novel role for the mTOR complexes in regulating RPE function, impacting retinal health and disease.},
}
@article {pmid39956680,
year = {2025},
author = {Zhao, F and Yang, L},
title = {Comment on "A deep learning approach for the screening of referable age-related macular degeneration - Model development and external validation".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2025.02.017},
pmid = {39956680},
issn = {0929-6646},
}
@article {pmid39955640,
year = {2025},
author = {Yoon, JM and Jung, SY and Han, KD and Shin, DW and Lim, DH and Chang, YS},
title = {Risk of allergic diseases in age-related macular degeneration: A nationwide cohort study in South Korea.},
journal = {Asian Pacific journal of allergy and immunology},
volume = {},
number = {},
pages = {},
doi = {10.12932/AP-280524-1865},
pmid = {39955640},
issn = {0125-877X},
abstract = {BACKGROUND: Premorbid allergic diseases are linked with the development of age-related macular degeneration (AMD), however, the risk of allergic diseases among patients with AMD is largely unknown.<br><br>OBJECTIVE: To evaluate the association between AMD with or without visual disability (VD) and the risk of allergic diseases.<br><br>METHODS: A total of 2,744,372 Individuals 50 years or older participated in the Korean National Health Screening Program in 2009 were categorized by presence of AMD and VD. Patients were followed until December 2019, and the prospective association of AMD and related VD with incident allergic diseases cases identified during the study period was investigated using the multivariable-adjusted Cox proportional hazard model.<br><br>RESULTS: During an average follow-up period of 5.87 years, 1,783,370 individuals were diagnosed with allergic diseases. Moreover, an increased risk of allergic diseases was observed in the group of individuals with AMD as compared to the control group (adjusted HR [aHR], 1.13; 95%CI, 1.11-1.14). The risk of atopic dermatitis or allergic rhinitis was more profound than that of asthma (aHR 1.12 [95%CI 1.07-1.18], aHR 1.13 [95%CI 1.11-1.14], and aHR 1.06 [95%CI 1.04-1.09], respectively). Furthermore, patients affected by AMD with VD were at an increased risk of atopic dermatitis (aHR 1.32, 95%CI 1.12-1.56) than those without VD (aHR 1.11, 95%CI 1.05-1.16) when compared with those in the control group.<br><br>CONCLUSIONS: AMD is associated with an increased risk of developing allergic diseases. Further investigations are required to elucidate the underlying mechanisms.},
}
@article {pmid39954920,
year = {2025},
author = {Chakravarthy, U and Schwartz, R and Guymer, RH and Holz, FG and Rachitskaya, AV and Vujosevic, S and Lewis, P and Vorwerk, H and Alibhai, AY and Moult, EM and Morales, MU and Bliss, C and Baumal, CR and Waheed, NK},
title = {Visual Function Benefit After Treatment With Pegcetacoplan: Microperimetry Analysis From the Phase 3 Oaks Trial.},
journal = {American journal of ophthalmology},
volume = {273},
number = {},
pages = {119-129},
doi = {10.1016/j.ajo.2025.02.012},
pmid = {39954920},
issn = {1879-1891},
mesh = {Humans ; Visual Field Tests ; *Visual Fields/physiology ; Aged ; *Visual Acuity/physiology ; Female ; Male ; *Geographic Atrophy/physiopathology/drug therapy/etiology/diagnosis ; Scotoma/physiopathology ; Tomography, Optical Coherence ; *Macular Degeneration/complications/physiopathology ; Aged, 80 and over ; Double-Blind Method ; Fluorescein Angiography ; Middle Aged ; Intravitreal Injections ; Retina/physiopathology ; Treatment Outcome ; Follow-Up Studies ; },
abstract = {PURPOSE: To evaluate the impact of pegcetacoplan on its ability to slow the loss of visual function using microperimetry endpoints in eyes with geographic atrophy secondary to age-related macular degeneration (AMD).<br><br>DESIGN: Post hoc analysis of phase 3 randomized controlled trial data.<br><br>METHODS: Utilizing data from the OAKS study, which evaluated pegcetacoplan monthly (PM) or every other month (PEOM) vs sham for the treatment of GA secondary to AMD, microperimetry endpoints were assessed at baseline and every 6 months until 24 months, using a 10-2 grid composed of 68 points with a 4-2 threshold strategy. Main outcome measures included the time to development of absolute scotomas in the 4 and 16 central macular points. The number of absolute scotomatous points and mean retinal sensitivity (dB) within the junctional zone extending to 250 &#xb5;m on either side of autofluorescence-determined GA border was analyzed for change from baseline.<br><br>RESULTS: Among 605 patients with subfoveal or nonsubfoveal GA, treatment with pegcetacoplan delayed time to development of absolute scotomas of all 4 central macular points compared to sham at 24 months (PM: hazard ratio [HR]: 0.66 [34% risk reduction]; 95% confidence interval [CI]: 0.46, 0.96; P = .0282; PEOM: HR: 0.64 [36% risk reduction]; 95% CI: 0.44, 0.92; P = .0164). Similarly, PM and PEOM treatment delayed time to development of absolute scotomas of all 16 central points (PM: HR: 0.57 [43% risk reduction]; 95% CI: 0.33, 0.96; P = .0361; PEOM: HR: 0.52 [48% risk reduction]; 95% CI: 0.32, 0.85; P = .0084). Across the junctional zone of GA, pegcetacoplan-treated eyes developed fewer absolute scotomatous points (PM difference vs sham pooled: -0.68 points, P = .1444; PEOM difference vs sham pooled: -1.14 points, P = .0140) and experienced decreased loss of mean retinal sensitivity (PM difference vs sham pooled: 0.56 dB, P = .0650; PEOM difference vs sham pooled: 0.71 dB, P = .0202) compared with sham at 24 months.<br><br>CONCLUSIONS: Microperimetry demonstrates a reduced rate of visual function loss in the central macula and junctional zone with pegcetacoplan treatment in GA due to AMD.},
}
@article {pmid39953740,
year = {2025},
author = {Li, B and Zhang, X and Fang, Y and Chen, M and Li, Q and Zeng, Y and Ren, C and Wang, C and Lv, Y and Lu, J and Liu, H and Liu, Y},
title = {PD-L1 Promotes Immunological Tolerance and Enhances Visual Protection of hESC-RPE Grafts in Retinal Degeneration.},
journal = {Cell proliferation},
volume = {58},
number = {8},
pages = {e70007},
pmid = {39953740},
issn = {1365-2184},
support = {2024YFA1108700//National Key Research and Development Program of China/ ; 81970843//National Natural Science Foundation of China/ ; CSTB2023NSCQ-LZX0166//Natural Science Foundation of Chongqing/ ; },
mesh = {*B7-H1 Antigen/metabolism/genetics/immunology ; Humans ; *Retinal Pigment Epithelium/transplantation/cytology/metabolism/immunology ; *Human Embryonic Stem Cells/cytology/metabolism/transplantation ; Animals ; *Immune Tolerance ; *Retinal Degeneration/therapy/immunology/pathology ; Mice ; Macular Degeneration/therapy/immunology ; Apoptosis ; Killer Cells, Natural/immunology ; },
abstract = {Immune rejection is a major barrier to the successful human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) transplantation for age-related macular degeneration (AMD). Traditional strategies to mitigate immune rejection involve ablating major histocompatibility complex (MHC) molecules on hESC-RPE. An alternative approach is immune checkpoint overexpression, avoiding natural killer (NK) cell-mediated destruction due to MHC-I deficiency. Our study highlights the benefits of PD-L1 overexpression without requiring MHC gene deletion, which preserved the immunosuppressive functions of hESC-RPE on NK cells. In Vivo experiments in retinal degeneration models showed that PD-L1-expressing hESC-RPE grafts exhibited significantly higher survival, reduced apoptosis and enhanced visual protection. Single-cell transcriptomics revealed reduced immune activation and oxidative stress in PD-L1-overexpressing grafts. PD-L1's protective role was further evidenced by improved light transduction in host photoreceptors. These findings support PD-L1 overexpression as a promising strategy to improve the efficiency of hESC-RPE-based therapy for AMD.},
}
@article {pmid39953504,
year = {2025},
author = {Zhang, J and Xiao, L and Zhao, X and Wang, P and Yang, C},
title = {Exploring the association between composite dietary antioxidant index and ocular diseases: a cross-sectional study.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {625},
pmid = {39953504},
issn = {1471-2458},
support = {12001470//National Natural Science Foundation of China/ ; 2020M671607//China Postdoctoral Science Foundation/ ; No. 2024111919126168//Guangdong Provincial Medical Science and Technology Research Fund/ ; },
mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; *Eye Diseases/epidemiology/prevention &amp; control ; *Antioxidants/administration &amp; dosage ; Nutrition Surveys ; *Diet/statistics &amp; numerical data ; Adult ; Aged ; },
abstract = {OBJECTIVE: Globally, approximately 2.2 billion people suffer from visual impairments or blindness. Dietary patterns are closely associated with the prevalence of multiple ocular diseases. This study aimed to explore the association between Composite Dietary Antioxidant Index (CDAI) and ocular disorders.<br><br>METHODS: The data were derived from 1706 subjects aged 40 years and older who participated in the 2005-2008 National Health and Nutrition Examination Survey (NHANES), which utilized undersampling techniques. Trained staff interviewed participants to gather information about their dietary habits using the 24-h diet recall method. The CDAI, incorporating six antioxidants, was then computed using a validated method. Eye diseases were diagnosed through a combination of examinations and questionnaires. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders.<br><br>RESULTS: After adjusting for potential confounders, higher CDAI quartiles (Q4) were significantly associated with reduced odds of diabetic retinopathy (OR: 0.55, P&#x2009;=&#x2009;0.041), cataracts (OR: 0.37, P&#x2009;<&#x2009;0.001), glaucoma (OR: 0.48, P&#x2009;=&#x2009;0.003), and macular degeneration (OR: 0.19, P&#x2009;<&#x2009;0.001). Carotenoids showed a significant negative correlation with ocular diseases, diabetic retinopathy (OR: 0.57, P&#x2009;<&#x2009;0.001), cataracts (OR: 0.75, P&#x2009;=&#x2009;0.014), glaucoma (OR: 0.59, P&#x2009;<&#x2009;0.001) and macular degeneration (OR: 0.55, P&#x2009;<&#x2009;0.001). Compared to the lowest quartile (Q1), higher quartiles (Q4) of zinc intake were associated with lower odds of DR (OR: 0.32, P&#x2009;<&#x2009;0.001) and glaucoma (OR: 0.73, P&#x2009;=&#x2009;0.001). Similarly, Q4 of vitamin C intake were associated with lower odds of cataracts (OR: 0.70, P&#x2009;=&#x2009;0.001) and glaucoma (OR: 0.71, P&#x2009;=&#x2009;0.003) compared to the Q1.<br><br>CONCLUSION: Higher CDAI scores are correlated with a decreased odds of ocular diseases, suggesting that an antioxidant-rich dietary pattern may be associated with better ocular health. Understanding these correlations could contribute to the development of preventive strategies and intervention measures for ocular diseases.},
}
@article {pmid39953382,
year = {2025},
author = {Zhou, X and Wu, J and Shen, Y and He, S and Guan, H and Shen, L},
title = {Genetically determined physical activity levels, sedentary behaviours, and their association with the risk of age-related macular degeneration.},
journal = {The Journal of international medical research},
volume = {53},
number = {2},
pages = {3000605251318198},
pmid = {39953382},
issn = {1473-2300},
mesh = {Humans ; *Macular Degeneration/genetics/epidemiology ; *Sedentary Behavior ; *Exercise ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Male ; Female ; Risk Factors ; Aged ; Polymorphism, Single Nucleotide ; Middle Aged ; Genetic Predisposition to Disease ; United Kingdom/epidemiology ; },
abstract = {OBJECTIVE: To investigate the causal effects of physical activity and sedentary traits on risk of Age-related macular degeneration (AMD).<br><br>METHODS: A two-sample Mendelian randomization (MR) analysis was used to investigate the causal relationship between physical activity and risk of AMD. We used genome-wide association studies (GWAS) summary statistics from two publicly available biobank-scale cohorts: UK Biobank and FinnGen. Physical activity data were self-reported by 703,901 UK Biobank participants and sedentary behaviour data were gathered from 159,606 FinnGen participants. Our analysis primarily used the inverse variance weighted (IVW) method.<br><br>RESULT: Engaging in moderate-to-vigorous physical activity significantly reduced the risk of AMD with an odds ratio of 0.77 (95% CI: 0.66-0.89). However, leisure screen time showed a slight but non-statistically significant upward trend. Sedentary behaviour at work, sedentary commuting showed no causal effects on AMD risk.<br><br>CONCLUSIONS: This study used MR analysis to examine the causal relationship between physical activity, sedentary behaviour, and AMD. It offers genetic evidence suggesting that physical activity may protect against AMD, emphasizing the significance of lifestyle factors in maintaining ocular health.},
}
@article {pmid39952954,
year = {2025},
author = {Arikan, M and Willoughby, J and Ongun, S and Sallo, F and Montesel, A and Ahmed, H and Hagag, A and Book, M and Faatz, H and Cicinelli, MV and Fawzi, AA and Podkowinski, D and Cilkova, M and De Almeida, DM and Zouache, M and Ramsamy, G and Lilaonitkul, W and Dubis, AM},
title = {OCT5k: A dataset of multi-disease and multi-graded annotations for retinal layers.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {267},
pmid = {39952954},
issn = {2052-4463},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retina/diagnostic imaging ; *Tomography, Optical Coherence ; Macular Degeneration/diagnostic imaging ; Machine Learning ; Image Processing, Computer-Assisted ; Algorithms ; Macular Edema/diagnostic imaging ; },
abstract = {Publicly available open-access OCT datasets for retinal layer segmentation have been limited in scope, often being small in size, specific to a single disease, or containing only one grading. This dataset improves upon this with multi-grader and multi-disease labels for training machine learning-based algorithms. The proposed dataset covers three subsets of scans (Age-related Macular Degeneration, Diabetic Macular Edema, and healthy) and annotations for two types of tasks (semantic segmentation and object detection). This dataset compiled 5016 pixel-wise manual labels for 1672 OCT scans featuring 5 layer boundaries for three different disease classes to support development of automatic techniques. A subset of data (566 scans across 9 classes of disease biomarkers) was subsequently labeled for disease features for 4698 bounding box annotations. To minimize bias, images were shuffled and distributed among graders. Retinal layers were corrected, and outliers identified using the interquartile range (IQR). This step was iterated three times, improving layer annotations' quality iteratively, ensuring a reliable dataset for automated retinal image analysis.},
}
@article {pmid39952571,
year = {2025},
author = {Kulkarni, NS and Josowitz, A and James, R and Liu, Y and Rayaprolu, B and Sagdullaev, B and Bhalla, AS and Shameem, M},
title = {Latest trends &amp; strategies in ocular drug delivery.},
journal = {Methods (San Diego, Calif.)},
volume = {235},
number = {},
pages = {100-117},
doi = {10.1016/j.ymeth.2025.02.003},
pmid = {39952571},
issn = {1095-9130},
mesh = {Humans ; *Drug Delivery Systems/methods/trends ; Administration, Ophthalmic ; Animals ; Intravitreal Injections/methods ; *Eye Diseases/drug therapy ; Macular Degeneration/drug therapy ; },
abstract = {Ocular drug delivery is one of the most challenging routes of administration, and this may be attributed to the complex interplay of ocular barriers and clearance mechanisms that restrict therapeutic payload residence. Most of the currently approved products that ameliorate ocular disease conditions are topical, i.e., delivering therapeutics to the outside anterior segment of the eye. This site of administration works well for certain conditions such as local infections but due to the presence of numerous ocular barriers, the permeation of therapeutics to the posterior segment of the eye is limited. Conditions such as age-related macular degeneration and diabetic retinopathy that contribute to an extreme deterioration of vision acuity require therapeutic interventions at the posterior segment of the eye. This necessitates development of intraocular delivery systems such as intravitreal injections, implants, and specialized devices that deliver therapeutics to the posterior segment of the eye. Frequent dosing regimens and high concentration formulations have been strategized and developed to achieve desired therapeutic outcomes by overcoming some of the challenges of drug clearance and efficacy. Correspondingly, development of suitable delivery platforms such as biodegradable and non-biodegradable implants, nano delivery systems, and implantable devices have been explored. This article provides an overview of the current trends in the development of suitable formulations &amp; delivery systems for ocular drug delivery with an emphasis on late-stage clinical and approved product. Moreover, this work aims to summarize current challenges and highlights exciting pre-clinical developments, and future opportunities in cell and gene therapies that may be explored for effective ocular therapeutic outcomes.},
}
@article {pmid39950589,
year = {2025},
author = {Michl, M and Gerendas, BS and Gruber, A and Goldbach, F and Mylonas, G and Leingang, O and Bühl, W and Sacu, S and Bogunovic, H and Sadeghipour, A and Schmidt-Erfurth, U},
title = {Comparison of AI-based retinal fluid monitoring in neovascular age-related macular degeneration with manual assessment by different eye care professionals under optimized conditions.},
journal = {Acta ophthalmologica},
volume = {103},
number = {5},
pages = {552-560},
pmid = {39950589},
issn = {1755-3768},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Subretinal Fluid/diagnostic imaging/metabolism ; *Wet Macular Degeneration/diagnosis/drug therapy/metabolism ; Female ; Male ; Aged ; *Ophthalmologists/standards ; Follow-Up Studies ; Aged, 80 and over ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; Reproducibility of Results ; *Artificial Intelligence ; Intravitreal Injections ; Visual Acuity ; },
abstract = {PURPOSE: To investigate whether automated intra- and subretinal fluid (IRF/SRF) volume measurements are equivalent to manual evaluations by eye care professionals from different backgrounds on real-world optical coherence tomography (OCT) images in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Routine OCT images (Spectralis, Heidelberg Engineering) were obtained during standard-of-care anti-VEGF treatment for nAMD at a tertiary referral centre. IRF/SRF presence and change (increase/decrease/stability) were assessed without time constraints by five retinologists, three ophthalmology residents, three general ophthalmologists, three orthoptists and three certified readers. Fluid volumes were segmented and quantified using a regulatory-approved AI-based tool (Vienna Fluid Monitor, RetInSight, Vienna, Austria). Sensitivity/specificity (Sen/Spe) for grading fluid presence and kappa agreement were calculated for each group. Their performances in distinguishing between IRF/SRF increase and decrease were assessed using AUCs.<br><br>RESULTS: About 124 follow-up visit pairs of 59 eyes with active nAMD were included. Across all five groups, fluid volumes >5&#x2009;nL were identified with values of 0.81-0.95 (Sen)/0.70-0.91 (Spe) for IRF and 0.89-0.98 (Sen)/0.74-0.90 (Spe) for SRF. Interpretations of IRF changes between -17&#x2009;nL and +3&#x2009;nL and SRF changes between -9.30&#x2009;nL and +6.50&#x2009;nL were associated with Sen&#x2009;>&#x2009;0.80 and Spe&#x2009;>&#x2009;0.87 among all groups. Agreements between the algorithm and groups in grading IRF/SRF presence ranged from &#x3ba;&#x2009;=&#x2009;0.69-0.82/0.73-0.79. The AUC for correctly classifying fluid change was >0.89 across all groups.<br><br>CONCLUSION: Eye care professionals with different levels of clinical expertise assessed disease activity on standard OCT images with comparable accuracy. Despite optimizing the methodology and time resources, manual performance did not reach the high level of automated fluid monitoring.},
}
@article {pmid39948402,
year = {2025},
author = {Acton, JH and McFadzean, J and Lau, CY and Foo, JW and Carson-Stevens, A},
title = {Patient safety in eye care: a multi-method analysis of reported incidents involving implementation of care and clinical assessment in England and Wales.},
journal = {Eye (London, England)},
volume = {39},
number = {8},
pages = {1486-1494},
pmid = {39948402},
issn = {1476-5454},
mesh = {Humans ; England/epidemiology ; Wales/epidemiology ; *Patient Safety/statistics &amp; numerical data ; *Ophthalmology/standards ; *Eye Diseases/therapy/diagnosis ; Male ; Female ; State Medicine ; *Medical Errors/statistics &amp; numerical data ; },
abstract = {BACKGROUND/OBJECTIVES: Patient safety is a global health priority, yet there is limited research into how ophthalmology is responding to this. There is evidence that a review of patient harm related to eye care and the associated patient safety incidents is needed. We aimed to characterise patient safety incidents involving eye care by: identifying the most frequently reported incidents involving clinical care; and characterising the nature of incidents leading to severe vision loss.<br><br>METHODS: The data comprised patient safety incidents reported between 2018 and 2022 to the National Reporting and Learning System and the NHS England Learn from Patient Safety Events system. Reports were searched for eye-related terms (ICD-11) and those reports relating to implementation of care and clinical assessment were included. A descriptive analysis was undertaken to characterise the most frequent incident types and their contributory factors, followed by a thematic analysis of incidents relating to severe vision loss.<br><br>RESULTS: Of the 836 reports identified, insufficient care (n&#x2009;=&#x2009;416) and delayed diagnosis (n&#x2009;=&#x2009;234) featured most. Patient harm occurred related to vision loss (n&#x2009;=&#x2009;449), delays in treatment (n&#x2009;=&#x2009;182), and disease progression (n&#x2009;=&#x2009;121). Among 220 reports that resulted in severe vision loss, patients with Glaucoma and Age-related Macular Degeneration were impacted by delays in monitoring and management, loss to follow-up, disease progression due to insufficient care and system failures.<br><br>CONCLUSIONS: In this characterisation of eye-related incident reports in a national population, potential areas of interest toward safer eye care include addressing delays in patients receiving care and insufficient care such as inconsistent monitoring in glaucoma.},
}
@article {pmid39947712,
year = {2025},
author = {Sambhara, D and Vakharia, P and Eichenbaum, DA},
title = {Real-world efficacy and safety of 8 mg aflibercept in neovascular AMD: a case series.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {39947712},
issn = {2397-3269},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Retrospective Studies ; Aged ; Male ; Female ; *Visual Acuity ; Treatment Outcome ; Aged, 80 and over ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Follow-Up Studies ; Tomography, Optical Coherence ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; },
abstract = {OBJECTIVE: This real-world retrospective case series evaluates the safety and efficacy of aflibercept 8 mg in patients diagnosed with neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSES: Treatment-na&#xef;ve or treatment-experienced patients with nAMD receiving aflibercept 8&#x2009;mg with at least 6&#x2009;months of follow-up were assessed.<br><br>RESULTS: 40 eyes from 33 patients were included, of which 36/40 eyes were previously treated. The mean age of subjects is 79.84 years. At baseline, 29/36 eyes had intraretinal fluid (IRF)/subretinal fluid (SRF) at an average interval of 40.97&#x2009;days, logMAR VA of 0.346, and average central subfield thickness (CST) of 341.53&#x2009;&#xb5;m. At final follow-up, average logMAR VA was 0.315 and average CST decreased by 39.39&#x2009;&#xb5;m, with an average number of days since last treatment of 52.9. Of the 32 eyes with IRF, SRF, or both at the time of switch, 12 eyes achieved anatomical quiescence without IRF/SRF after the first injection of aflibercept 8&#x2009;mg, including three of four treatment-naive patients.<br><br>CONCLUSIONS: This early case series suggests that patients treated with aflibercept 8&#x2009;mg may achieve greater duration between treatments while preserving and, in some cases, improving visual acuity and anatomical outcomes in a real-world clinic setting. In this retrospective study, the patient population primarily consisted of treatment-experienced cases with recalcitrant disease or high treatment burdens, potentially using aflibercept 8&#x2009;mg as salvage therapy. This selection bias limits generalisability to broader real-world populations. The small sample size precludes formal statistical conclusions. Multiple investigators made unstandardised treatment decisions based on individual clinical judgement, including whether to continue aflibercept 8&#x2009;mg or revert to prior therapy, sometimes after just one injection.},
}
@article {pmid39947311,
year = {2025},
author = {Chen, C and Yang, J and Wang, H and Lei, Y and Diao, Y},
title = {Involvement of STAT3 activation in ameliorating all-trans-retinal-induced ferroptosis in photoreceptor-derived 661W cells in vitro.},
journal = {Experimental eye research},
volume = {253},
number = {},
pages = {110280},
doi = {10.1016/j.exer.2025.110280},
pmid = {39947311},
issn = {1096-0007},
mesh = {*Ferroptosis/drug effects/physiology ; *STAT3 Transcription Factor/metabolism ; Animals ; Mice ; Reactive Oxygen Species/metabolism ; *Photoreceptor Cells, Vertebrate/metabolism/drug effects/pathology ; *Retinaldehyde/pharmacology ; Phosphorylation ; Lipid Peroxidation ; Blotting, Western ; Mice, Inbred C57BL ; Cells, Cultured ; },
abstract = {Ferroptosis, a form of iron-dependent programmed cell death, has emerged as a critical player in various diseases, including retinal degenerative disorders. Previous studies have highlighted that ferroptosis, triggered by all-trans-retinal (atRAL) accumulation in photoreceptor cells, contributes significantly to the pathogenesis of dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1). However, the underlying molecular mechanisms regulating this process remain poorly understood. In this study, we explore the involvement of signal transducer and activator of transcription 3 (STAT3) in the regulation of atRAL-induced 661W photoreceptor cells (mouse-derived photoreceptor cells) ferroptosis. We found that atRAL treatment induces phosphorylation of STAT3 in 661W photoreceptor cells. Meanwhile, we also discovered that the accumulation of Reactive oxygen species (ROS) induced by atRAL partly contributes to the activation of STAT3 in 661W photoreceptor cells. Importantly, our data suggest that inhibition of STAT3 phosphorylation, resulting in increased lipid peroxidation through upregulation of the acyl-CoA synthetase long-chain family member 4 (ACSL4) and prostaglandin-endoperoxide synthase 2 (PTGS2) gene, exacerbates ferroptosis in atRAL-loaded 661W photoreceptor cells. Additionally, our findings further confirm that STAT3 activator Colivelin may significantly reduce ferroptosis in 661W photoreceptor cells exposed to atRAL by regulating the ACSL4 and PTGS2 gene. Overall, these results revealed that activated STAT3 mitigates atRAL-induced ferroptosis in photoreceptor cells, possibly by reducing ACSL4 and PTGS2 gene expression. This pathway highlights the therapeutic potential of STAT3 as a novel target for treating dry AMD and STGD1.},
}
@article {pmid39946351,
year = {2025},
author = {Kumar Mishra, S and Shah, R and Gogate, P and Sapkota, YD and Gurung, R and Shrestha, MK and Mactaggart, I and McCormick, I and Shahi, BB and Khandekar, R and Burton, M},
title = {Prevalence and causes of blindness and vision impairment among people 50 years and older in Nepal: A national Rapid Assessment of Avoidable Blindness survey.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0309037},
pmid = {39946351},
issn = {1932-6203},
mesh = {Humans ; Nepal/epidemiology ; Female ; Male ; *Blindness/epidemiology/etiology ; Middle Aged ; Aged ; Prevalence ; Cross-Sectional Studies ; Aged, 80 and over ; Cataract/epidemiology/complications ; Visual Acuity ; *Vision Disorders/epidemiology/etiology ; *Vision, Low/epidemiology/etiology ; },
abstract = {PURPOSE: To determine the prevalence and causes of blindness and vision impairment among people 50 years and older in Nepal.<br><br>METHODS: We conducted seven provincial-level Rapid Assessment of Avoidable Blindness (RAAB) cross-sectional, population-based surveys between 2018-2021. Provincial prevalence estimates were weighted to give nationally representative estimates. Sampling, enumeration, and examination of the population 50 years and older were done at the province level following standard RAAB protocol.<br><br>RESULTS: Across seven surveys, we enrolled 33,228 individuals, of whom 32,565 were examined (response rate 98%). Females (n = 17,935) made up 55% of the sample. The age-sex-province weighted national prevalence of blindness (better eye presenting visual acuity <3/60) was 1.1% (95% confidence interval [CI] 1.0-1.2%), and any vision impairment <6/12 was 20.7% (95% CI 19.9-21.5%). The prevalence of blindness was higher in women than men (1.3% [95% CI 1.1-1.5%] vs 0.9% [95% CI 0.7-1.0%]). Age-sex weighted blindness prevalence was highest in Lumbini Province (1.8% [95% CI 1.3-2.2%]) and lowest in Bagmati Province (0.7% [95% CI 0.4-0.9%]) and Sudurpaschim Province (0.7% [95% CI 0.4-0.9%]). Cataract (65.2%) was the leading cause of blindness in our sample, followed by corneal opacity (6.4%), glaucoma (5.8%) and age-related macular degeneration (5.3%). Other posterior segment diseases accounted for 8.4% of cases. Cataract was also the leading cause of severe vision impairment (83.9%) and moderate vision impairment (66.8%), while refractive error was the leading cause of mild vision impairment (66.5%).<br><br>CONCLUSION: The prevalence of blindness was higher among women than men and varied by province. The Lumbini and Madesh Provinces in the Terai (plains) region had higher prevalence of blindness than elsewhere. Cataract was the leading cause of blindness, severe vision impairment and moderate vision impairment while refractive error was the leading cause of mild vision impairment.},
}
@article {pmid39946136,
year = {2025},
author = {Ding, X and Zhou, X and Liu, X and Lai, Y and Yan, W and Cheng, Y and Hou, A and Chen, L and Sun, L},
title = {Targeting Runx1 in Pathological Retinal Angiogenesis: A Potential Therapeutic Approach.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {2},
pages = {40},
pmid = {39946136},
issn = {1552-5783},
mesh = {Animals ; *Retinal Neovascularization/metabolism/genetics/pathology ; Mice ; *Core Binding Factor Alpha 2 Subunit/genetics ; Humans ; Disease Models, Animal ; *Retinal Vessels/metabolism/pathology ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells ; Signal Transduction ; Mice, Knockout ; Blotting, Western ; Cell Proliferation ; Cells, Cultured ; *Gene Expression Regulation/physiology ; Angiogenesis ; },
abstract = {PURPOSE: Neovascular eye diseases, such as proliferative diabetic retinopathy (PDR), wet age-related macular degeneration (wAMD) and retinopathy of prematurity (ROP), are major causes of vision loss and blindness worldwide. Our transcription factor motif enrichment analysis highlighted RUNX1 as a key regulator in the hypoxic response. The purpose of this study was to characterize how loss of Runx1 affects physiological and pathological retinal vasculature formation.<br><br>METHODS: RNA-seq analysis and Transcription factor motif enrichment analysis were conducted in hypoxic and normoxic HUVECs. Conditional deletion of Runx1 in endothelial cells In mice was achieved using recombinase driver Cdh5-CreERT2. Vascular coverage, density, vessel progression, branchpoints, and sprout numbers was measured in retina of Runx1iECKO mice. The expression patterns, functions, and potential therapeutic value of RUNX1 were further explored with clinical samples, as well as in vivo and in vitro experiments. Bioinformatics and high-throughput sequencing were performed to identify potential target genes of Runx1. RT-qPCR and Western blot analyses were carried out to detect the changes of PI3-kinase/AKT/mTOR pathway.<br><br>RESULTS: Loss of Runx1 in mice resulted in a reduction of the vascular coverage, density, vessel progression, branchpoints, and sprouts numbers of the retinal vascular network during its development. Notably, mature blood vessels remained unaffected by Runx1 inhibition. Upregulation of RUNX1 was observed in patients with PDR and ROP. RUNX1 Inhibition reduced endothelial cell proliferation, migration and tubule formation, leading to decreased pathological neovascularization, which is shown in oxygen-induced retinopathy. Mechanistically, in vitro experiments demonstrated that RUNX1 regulates EC angiogenesis through the PI3K/AKT/mTOR signaling pathway.<br><br>CONCLUSIONS: Runx1 is essential for physiological retinal vascularization. RUNX1 Inhibition may effectively decrease pathological neovascularization. Our findings suggest that targeting RUNX1 could be a promising therapeutic strategy for retinal neovascular disorders, preserving the integrity of mature blood vessels while selectively inhibiting neovascularization.},
}
@article {pmid39945259,
year = {2025},
author = {Qin, L and Gao, X and Lu, X and Liu, W and Tian, J and Yuan, G},
title = {Investigation of LncRNA Expression Profiles and Analysis of Immune-Related lncRNA-miRNA-mRNA Networks in Neovascular Age-Related Macular Degeneration.},
journal = {Combinatorial chemistry &amp; high throughput screening},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113862073342212250102042734},
pmid = {39945259},
issn = {1875-5402},
abstract = {INTRODUCTION: Age-related Macular Degeneration (AMD) is a predominant cause of blindness in the elderly. The present study is the first to investigate the alteration of lncRNAs and mRNAs in neovascular AMD.<br><br>METHODS: Nine patients with neovascular AMD were included in the study. The control group comprised seven patients with epiretinal membranes. RNA sequencing was performed to obtain the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs). Then, the DElncRNA-DEmRNA co-expression network, ceRNA network, and immune-related ceRNA subnetwork were constructed. Functional annotation of DEmRNAs between the two groups and DEmRNAs in networks was conducted. The immune cell distribution in neovascular AMD was also evaluated. Real-time qPCR (RT-qPCR) was used to validate the expression levels of key markers.<br><br>RESULTS: A total of 342 DEmRNAs and 157 DElncRNAs were obtained in neovascular AMD. Functional annotation indicated that these DEmRNAs significantly enriched immune systemrelated processes, such as positive regulation of B cell activation, immunoglobulin receptor binding, complement activation, and classical pathway. The DElncRNA-DEmRNA co-expression network, including 185 DElncRNA-DEmRNA co-expression pairs, and the ceRNA (DElncRNA-miRNA-DEmRNA) network, containing 45 lncRNA-miRNA pairs and 73 miRNAmRNA pairs, were constructed. The immune-related ceRNA subnetwork, including 2 lncRNAs, 5 miRNAs, and 3 mRNAs, was constructed. In addition, the distribution of immune cells was slightly different between the neovascular AMD group and the control group. RT-qPCR validation indicated the consistency between the RT-qPCR results and RNA sequencing results.<br><br>CONCLUSION: In conclusion, STC1, S100A1, MEG3, MEG3-hsa-miR-608-S100A1, and MEG3- hsa-miR-130b-3p/hsa-miR-149-3p-STC1 may be related to the occurrence and development of neovascular AMD.},
}
@article {pmid39943980,
year = {2025},
author = {Kiel, C and Weber, BHF},
title = {Diagnostic testing in the genetically complex age-related macular degeneration.},
journal = {Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V},
volume = {37},
number = {1},
pages = {27-35},
pmid = {39943980},
issn = {1863-5490},
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment with the risk of developing the disease influenced by a combination of genetic and environmental factors. With the recent expansion of treatment options, enhancing diagnostic accuracy and improving access to treatment are increasingly becoming the focus of interest. By using data from genome-wide association studies (GWAS) to generate polygenic risk scores (PRS), an assessment of an individual's genetic risk for AMD is feasible. While the predictive accuracy of the AMD-PRS is most robust for individuals at very high genetic risk, genetic diagnostic testing is warranted due to the large number of affected individuals resulting from the high prevalence of AMD. Early genetic confirmation of AMD-related pathology can facilitate timely treatment initiation, potentially improving patient outcomes.},
}
@article {pmid39942561,
year = {2025},
author = {Ribeiro, A and Oliveira, D and Cabral-Marques, H},
title = {Curcumin in Ophthalmology: Mechanisms, Challenges, and Emerging Opportunities.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {3},
pages = {},
pmid = {39942561},
issn = {1420-3049},
mesh = {*Curcumin/therapeutic use/pharmacology/chemistry ; Humans ; Animals ; *Eye Diseases/drug therapy/metabolism ; Nanoparticles/chemistry ; Drug Delivery Systems ; Ophthalmology ; },
abstract = {Ocular diseases affecting the anterior and posterior segments of the eye are major causes of global vision impairment. Curcumin, a natural polyphenol, exhibits anti-inflammatory, antioxidant, antibacterial, and neuroprotective properties, making it a promising candidate for ocular therapy. However, its clinical use is hindered by low aqueous solubility, poor bioavailability, and rapid systemic elimination. This review comprehensively highlights advances in curcumin delivery systems aimed at overcoming these challenges. Emerging platforms, including proniosomal gels, transferosomes, and cyclodextrin complexes, have improved solubility, permeability, and ocular retention. Nanoparticle-based carriers, such as hybrid hydrogels and biodegradable nanoparticles, enable sustained release and targeted delivery, supporting treatments for posterior segment diseases like diabetic retinopathy and age-related macular degeneration. For anterior segment conditions, including keratitis and dry eye syndrome, cyclodextrin-based complexes and mucoadhesive systems enhance corneal permeability and drug retention. Mechanistically, curcumin modulates key pathways, such as NF-κB and TLR4, reducing oxidative stress, angiogenesis, and apoptosis. Emerging strategies like photodynamic therapy and neuroprotective approaches broaden their application to eyelid conditions and neuroinflammatory ocular diseases. These advancements address curcumin's pharmacokinetic limitations, supporting its clinical translation into ophthalmic therapies. This work underscores curcumin's potential in ocular disease management and advocates clinical trials to validate its safety, efficacy, and therapeutic relevance.},
}
@article {pmid39941390,
year = {2025},
author = {Samanta, A and Driban, M and Sahoo, N and Parameswarappa, D and Singh, SR and Caplash, S and Mishra, P and Agrawal, R and Venkatesh, R and Maltsev, DS and Chhablani, J},
title = {Central Serous Chorioretinopathy and Ocular Comorbidities.},
journal = {Journal of clinical medicine},
volume = {14},
number = {3},
pages = {},
pmid = {39941390},
issn = {2077-0383},
abstract = {Background/Objectives: Central serous chorioretinopathy (CSCR) is a common retinopathy that can present with other concurrent diseases; thus, further research into the prevalence of other ocular comorbidities in eyes with CSCR is required. Methods: This retrospective, multicentric, cross-sectional observational study reviewed the charts of 9157 patients. Of them, 579 (6.32%) patients and 766 eyes had an additional ocular comorbidity, in addition to CSCR, in at least one subject eye. Results: The baseline best-corrected visual acuity (BCVA) of the subjects eyes was 0.49 ± 0.36 logMAR. The average BCVA of subject eyes with coexisting macular diseases was 0.50 logMAR, while the corresponding BCVA of subject eyes with coexisting peripheral disease was 0.55 logMAR. The most prevalent coexisting macular diseases were non-proliferative diabetic retinopathy (26.8%), non-exudative age-related macular degeneration (AMD) (7.6%) and hypertensive retinopathy (3.0%). The most prevalent coexisting non-macular diseases were lattice degeneration (8.9%), optic atrophy (5.1%), rhegmatogenous retinal detachment (1.70%) and optic disc pit (1.7%). The odds of having a comorbid disease in the same eye as CSCR were statistically significant for branch retinal vein occlusion (OR 11.56, p-value = 0.02) and non-exudative AMD (OR 2.06; p-value = 0.01); additionally, there was a trend towards significance for idiopathic polypoidal choroidal vasculopathy (OR 4.43; p-value = 0.05) when compared to the eyes without CSCR. Conclusions: Certain diseases are more likely to coexist in eyes with CSCR. Additionally, eyes with CSCR may have statistically significant odds of certain diseases when compared to eyes without CSCR.},
}
@article {pmid39941302,
year = {2025},
author = {Kim, J and Han, BS and Ha, JE and Park, MS and Kwon, S and Cho, BJ},
title = {Prediction of the Cause of Fundus-Obscuring Vitreous Hemorrhage Using Machine Learning.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {3},
pages = {},
pmid = {39941302},
issn = {2075-4418},
support = {NRF-2022R1C1C1010643//National Research Foundation of Korea/ ; },
abstract = {Objectives: This study aimed to predict the unknown etiology of fundus-obscuring vitreous hemorrhage (FOVH) based on preoperative conditions using machine learning (ML) and to identify key preoperative factors. Methods: Medical records of 223 eyes from 204 patients who underwent vitrectomy for FOVH of unknown etiology between January 2012 and July 2022 were retrospectively reviewed. Preoperative data, including demographic information, systemic disease, ophthalmic history, and retinal status of the unaffected eye, were collected. The postoperatively identified etiologies of FOVH were categorized into six groups: proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO) or rupture of retinal arterial macroaneurysm, neovascular age-related macular degeneration (nAMD), retinal tear, Terson syndrome, and other causes. Four ML algorithms were trained and evaluated using seven-fold cross-validation. Results: The ML algorithms achieved mean accuracies of 76.2% for artificial neural network, 74.5% for XG-Boost, 74.4% for LASSO logistic regression, and 68.5% for decision tree. Key predictive factors commonly selected by the ML algorithms included PDR in the fellow eye, underlying diabetes mellitus, subarachnoid hemorrhage, and a history of retinal tear, RVO, or nAMD in the affected eye. Conclusions: The unknown etiology of FOVH could be predicted preoperatively with considerable accuracy by ML algorithms. Previous ophthalmic conditions in the affected eye and the condition of the fellow eye were important variables for prediction. This approach might assist in determining appropriate treatment plans.},
}
@article {pmid39939555,
year = {2025},
author = {Borrelli, E and Mohammed, AR and Barresi, C and Vupparaboina, KK and Viggiano, P and Boscia, F and Berni, A and Introini, U and Reibaldi, M and Bandello, F and Chhablani, J},
title = {Capturing the transition from intermediate to neovascular AMD: Longitudinal changes in choroidal volume and choroidal vascularity index.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {5},
pages = {1289-1296},
pmid = {39939555},
issn = {1435-702X},
mesh = {Humans ; *Choroid/blood supply/pathology ; *Tomography, Optical Coherence/methods ; Male ; Female ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/diagnosis/drug therapy/physiopathology ; Aged ; Follow-Up Studies ; Intravitreal Injections ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Disease Progression ; Visual Acuity ; Organ Size ; Fundus Oculi ; Aged, 80 and over ; Retrospective Studies ; Time Factors ; Imaging, Three-Dimensional ; Ranibizumab/administration &amp; dosage ; *Retinal Vessels/pathology ; },
abstract = {BACKGROUND: To perform a three-dimensional assessment of the choroid, including choroidal volume and choroidal vascularity index (CVI), during the transition from intermediate to neovascular age-related macular degeneration (AMD), and following anti-VEGF therapy.<br><br>METHODS: A total of 42 participants (42 eyes) with intermediate AMD at baseline who developed neovascular AMD within 3 months were included in the analysis. Optical coherence tomography (OCT) scans at follow-up visits (after transition to neovascular AMD and 12 months after the initiation of anti-VEGF therapy) were compared with values at the latest visit with evidence of intermediate AMD to quantify longitudinal choroidal changes. Enhanced depth imaging (EDI) OCT scans were analyzed to obtain the following metrics: (i) choroidal volume, (ii) choroidal stromal volume, (iii) choroidal vascular volume, and (iv) CVI.<br><br>RESULTS: At baseline, the mean (median; IQR) choroidal volume (i.e., including both the stromal and vascular components) was 0.156&#xa0;mm&#xb3; (0.149; 0.065), increasing to 0.163&#xa0;mm&#xb3; (0.148; 0.068) at the follow-up when treatment-na&#xef;ve exudative MNV was first detected (p&#x2009;=&#x2009;0.013). After 12 months of anti-VEGF therapy, it returned to near-baseline levels at 0.156&#xa0;mm&#xb3; (0.146; 0.065; p&#x2009;=&#x2009;0.457). Similarly, the choroidal stromal and choroidal volumes increased at MNV detection but returned to baseline after treatment. Conversely, no alterations in CVI were observed between the baseline and follow-up visits.<br><br>CONCLUSION: The transition from intermediate to exudative neovascular AMD is associated with a significant increase in choroidal volume, affecting both stromal and luminal components. After anti-VEGF treatment, these changes regress, returning to baseline levels.},
}
@article {pmid39939121,
year = {2025},
author = {Pandey, PU and Micieli, JA and Ong Tone, S and Eng, KT and Kertes, PJ and Wong, JCY},
title = {Realistic fundus photograph generation for improving automated disease classification.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {7},
pages = {791-798},
pmid = {39939121},
issn = {1468-2079},
mesh = {Humans ; Fundus Oculi ; *Neural Networks, Computer ; *Retinal Diseases/classification/diagnosis ; *Photography/methods ; ROC Curve ; Diabetic Retinopathy ; Deep Learning ; Macular Degeneration ; },
abstract = {AIMS: This study aims to investigate whether denoising diffusion probabilistic models (DDPMs) could generate realistic retinal images, and if they could be used to improve the performance of a deep convolutional neural network (CNN) ensemble for multiple retinal disease classification, which was previously shown to outperform human experts.<br><br>METHODS: We trained DDPMs to generate retinal fundus images representing diabetic retinopathy, age-related macular degeneration, glaucoma or normal eyes. Eight board-certified ophthalmologists evaluated 96 test images to assess the realism of generated images and classified them based on disease labels. Subsequently, between 100 and 1000 generated images were employed to augment training of deep convolutional ensembles for classifying retinal disease. We measured the accuracy of ophthalmologists in correctly identifying real and generated images. We also measured the classification accuracy, F-score and area under the receiver operating curve of a trained CNN in classifying retinal diseases from a test set of 100 fundus images.<br><br>RESULTS: Ophthalmologists exhibited a mean accuracy of 61.1% (range: 51.0%-68.8%) in differentiating real and generated images. Augmenting the training set with 238 generated images in the smallest class statistically significantly improved the F-score and accuracy by 5.3% and 5.8%, respectively (p<0.01) in a retinal disease classification task, compared with a baseline model trained only with real images.<br><br>CONCLUSIONS: Latent diffusion models generated highly realistic retinal images, as validated by human experts. Adding generated images to the training set improved performance of a CNN ensemble without requiring additional real patient data.},
}
@article {pmid39937692,
year = {2025},
author = {Kalavar, M and Sridhar, J},
title = {Clinical trials and real-world studies examining faricimab and high-dose aflibercept for wet age-related macular degeneration and diabetic macular edema.},
journal = {Current opinion in ophthalmology},
volume = {36},
number = {3},
pages = {189-198},
doi = {10.1097/ICU.0000000000001129},
pmid = {39937692},
issn = {1531-7021},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Macular Edema/drug therapy/diagnosis/etiology ; *Diabetic Retinopathy/drug therapy/diagnosis ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Clinical Trials as Topic ; Dose-Response Relationship, Drug ; Antibodies, Bispecific ; },
abstract = {PURPOSE OF REVIEW: The goal of this review is to summarize emerging clinical trial and real world evidence for faricimab and high dose aflibercept (8 mg), two recently approved treatments for wet age-related macular degeneration and diabetic macular edema.<br><br>RECENT FINDINGS: Faricimab, a bispecific monoclonal antibody targeting vascular endothelial growth factor (VEGF) and angiopoietin-2, and high-dose aflibercept have demonstrated significant potential for extending treatment intervals while maintaining efficacy. Pivotal clinical trials such as YOSEMITE, and RHINE established faricimab to be noninferior to standard anti-VEGF therapy with superior durability. Real-world data corroborated these results, demonstrating improved anatomic outcomes with extended treatment intervals, though improvements in best corrected visual acuity (BCVA) remains varied. High-dose aflibercept has similarly demonstrated noninferiority in landmark clinical trials such as PHOTON and PULSAR, with extended dosing intervals. However, comprehensive real-world data for high dose aflibercept remains limited and warrants further investigation.<br><br>SUMMARY: Both faricimab and high-dose aflibercept show promise in reducing treatment burden for wet age-related macular degeneration and diabetic macular edema through extended dosing intervals while maintaining or improving clinical outcomes compared to standard anti-VEGF therapy. Faricimab has demonstrated this both in clinical trials as well as real-world studies, while high-dose aflibercept has demonstrated similar durability in trials but requires additional real-world evidence.},
}
@article {pmid39937567,
year = {2025},
author = {Yanai, R and Yasunaga, G and Tsuji, S and Honda, T and Iwata, A and Miyagawa, E and Yoshida, K and Kishimoto, M and Sakai, H and Fujise, Y and Asagiri, M and Mitamura, Y},
title = {Dietary intake of whale oil-containing ω-3 long-chain polyunsaturated fatty acids attenuates choroidal neovascularization in mice.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {4},
pages = {e70378},
pmid = {39937567},
issn = {1530-6860},
support = {JP24K12808//Japan Society for the Promotion of Science London (JSPS)/ ; },
mesh = {Animals ; *Choroidal Neovascularization/pathology/metabolism/diet therapy/prevention &amp; control/drug therapy ; *Fatty Acids, Omega-3/administration &amp; dosage/pharmacology/blood ; Mice ; Mice, Inbred C57BL ; Macular Degeneration ; Male ; Choroid/metabolism/drug effects ; Retina/metabolism/drug effects ; Cytokines/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in Western and developing countries. Since antivascular endothelial growth factor (VEGF) therapy is available for the regression of choroidal neovascularization (CNV), it does not work for the pathophysiology of AMD so a cure is increasingly demanded. Whale oil promotes various bodily functions, such as anti-inflammatory effects for cardiovascular disease, but its physiological mechanisms are still unclarified. Here, we examined the effects of whale oil on a mouse model of AMD. The area of CNV measured in choroidal flat-mount preparations at 7 days after laser photocoagulation was significantly smaller in mice fed whale oil compared with control mice free of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs). The plasma concentrations of ω-3 LCPUFAs were higher, whereas those of ω-6 LCPUFAs were lower in mice fed the diet containing whale oil than in those fed the control diet. The concentrations of various inflammatory cytokines and chemokines in the retina or choroid at 3 or 7 days after CNV induction differed between the two groups of mice. Furthermore, the concentration of VEGF was decreased in the retina but increased in the choroid at 7 or 3 days after photocoagulation, respectively. Our results thus show that dietary intake of whale oil-containing ω-3 LCPUFAs attenuated CNV in association with changes in inflammatory mediator levels and VEGF expression in the retina and choroid of mice, and it, therefore, warrants further study as a means to protect against AMD in humans.},
}
@article {pmid39937494,
year = {2025},
author = {Chen, Y and Zhang, X and Zhang, Y and Zhang, S and Huo, Y and Wu, Y and Shen, L and Mao, J},
title = {Metabolomic Characteristics of Aqueous Humor in Wet Age-Related Macular Degeneration and the Impact of Anti-VEGF Treatment.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {2},
pages = {37},
pmid = {39937494},
issn = {1552-5783},
mesh = {Humans ; *Aqueous Humor/metabolism ; Female ; Male ; *Wet Macular Degeneration/drug therapy/metabolism ; *Metabolomics/methods ; Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Chromatography, High Pressure Liquid ; Tandem Mass Spectrometry ; Intravitreal Injections ; Aged, 80 and over ; ROC Curve ; Ranibizumab/therapeutic use ; Bevacizumab/therapeutic use ; },
abstract = {PURPOSE: To explore the alterations in metabolites of wet age-related macular degeneration (wAMD) by conducting metabolomics in aqueous humor from patients with wAMD and to assess the potential effects of anti-vascular endothelial growth factor (anti-VEGF) on these metabolites.<br><br>METHODS: Metabolomic analysis was performed on the aqueous humor of 30 patients with wAMD receiving anti-VEGF treatments and 20 controls, via ultra-high performance liquid chromatography tandem mass spectrometry. The aqueous humor samples collected from untreated patients with wAMD were classified as the pre-wAMD group. Accordingly, the samples collected from patients with wAMD receiving one anti-VEGF treatment were designated as the post-wAMD group. Individuals were further classified into responders and nonresponders according to their reaction to the treatment. Principal component analysis, hierarchical cluster analysis, and the Kyoto Encyclopedia of Genes and Genomes annotation and enrichment analysis, were subsequently performed. Machine learning and receiver operating characteristic curve analyses were used to further analyze potential vital metabolites.<br><br>RESULTS: Among the 1001 metabolites verified in the aqueous humor, 306 compounds separated patients with pre-wAMD from the control group, whereas 68 metabolites differentiated patients with post-wAMD and patients with pre-wAMD. Enrichment in metabolic pathways was noted in ABC transporters, thiamine metabolism, glycerophospholipid metabolism, mammalian target of rapamycin signaling pathway and tyrosine metabolism, and so on. Machine learning and receiver operating characteristic curves analysis suggested that &#x3b4;-valerolactam could not only distinguish between patients with wAMD and the control group, but also differentiate between patients with post-wAMD and patients with pre-wAMD. Changes in acylcarnitine were observed in anti-VEGF responders with wAMD.<br><br>CONCLUSIONS: There were noticeable alterations in the aqueous humor of patients with wAMD involving many metabolites that are associated with ABC transporters, glycerophospholipid metabolism, and the mammalian target of rapamycin signaling pathway. It is possible that &#x3b4;-valerolactam can be applied as a biomarker in wAMD.},
}
@article {pmid39937341,
year = {2025},
author = {Tanaka, K and Omori, T and Oguchi, Y and Itagaki, K and Kato, Y and Honjo, J and Norikawa, K and Sugano, Y and Mukai, R and Ishida, Y and Machida, T and Sekine, H and Sekiryu, T},
title = {HTRA1 and complement activation in neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {3},
pages = {453-459},
pmid = {39937341},
issn = {1613-2246},
mesh = {Humans ; *High-Temperature Requirement A Serine Peptidase 1/metabolism/genetics ; Male ; Female ; Cross-Sectional Studies ; Aged ; *Wet Macular Degeneration/metabolism/genetics/diagnosis ; *Aqueous Humor/metabolism ; *Complement Activation/physiology ; Genotype ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/metabolism ; Middle Aged ; Tomography, Optical Coherence ; Fluorescein Angiography ; Proteins ; },
abstract = {PURPOSE: To investigate the relationship between high temperature requirement A (HTRA1) and the local complement system, we measured HTRA1 and complement activation products in the aqueous humor of patients with neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Surveys (cross-sectional studies).<br><br>METHODS: One hundred twenty-one eyes of 121 patients with nAMD and 55 control eyes were enrolled. HTRA1, complement activation products (C3a and C4a), and proinflammatory cytokines (vascular endothelial growth factor [VEGF] and monocyte chemoattractant protein-1) were measured. Genotyping of ARMS2 A69S, in linkage disequilibrium with the HTRA1 gene, was performed in all patients and controls.<br><br>RESULTS: The respective GG, GT, and TT genotypes for ARMS2 A69S were distributed as follows: 23 (19.0%), 54 (44.6%), and 44 (36.4%) in nAMD patients, and 26 (47.3%), 22 (40.0%), and 7 (12.7%) in controls, (p&#x2009;<&#x2009;0.001). HTRA1 concentrations in the aqueous humor were higher in nAMD (994 pg/ml; interquartile range, 743-1450) than controls (794 pg/ml; 490-1325). The difference in the HTRA1 concentrations in the aqueous humor between each genotype of ARMS2 A69S was not significant (GG genotype: 857 pg/ml; 508-1115, GT genotype: 957 pg/ml; 758-1474, TT genotype: 1,141 pg/ml; 757-1663, p&#x2009;=&#x2009;0.1417). VEGF and C3a concentrations in the eyes with the risk allele (T allele) were significantly higher than those with the non-risk allele (p&#x2009;=&#x2009;0.0400 and p&#x2009;=&#x2009;0.0197, respectively). HTRA1 concentration was correlated with only the VEGF concentration (&#x3c1;&#x2009;=&#x2009;0.3651, p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: Concentrations of HTRA1 in the aqueous humor were not increased in patients with the ARMS2 risk allele and did not correlate with C3a and C4a concentrations. HTRA1 concentrations in aqueous humor do not reflect local complement activation in nAMD.},
}
@article {pmid39936047,
year = {2024},
author = {Ceran, TH and Citirik, M and Teke, MY},
title = {Risk of complications in patients with one eye during and after ocular surgery.},
journal = {Romanian journal of ophthalmology},
volume = {68},
number = {4},
pages = {409-414},
pmid = {39936047},
issn = {2501-2533},
mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Postoperative Complications/epidemiology ; Aged ; *Intraoperative Complications/epidemiology ; Middle Aged ; *Blindness/etiology/epidemiology ; *Retinal Detachment/surgery ; Visual Acuity ; Risk Factors ; *Vitreoretinal Surgery/adverse effects ; *Phacoemulsification/adverse effects ; Aged, 80 and over ; Follow-Up Studies ; Incidence ; },
abstract = {PURPOSE: This study examined patients with permanent legal blindness in one eye after a previous eye surgery and those with permanent legal blindness in one eye for non-surgical reasons. The objective of this study was to assess the occurrence of complications both during and after surgery in patients undergoing phacoemulsification for cataracts or vitreoretinal surgery for retinal detachment in the fellow eye.<br><br>METHODS: A retrospective study included 62 patients (group 1) with legal blindness in one eye, compared to 62 control patients (group 2) undergoing similar surgeries. Complications, history of complex surgery leading to legal blindness, and demographic characteristics were analyzed.<br><br>RESULTS: In group 1, the complication rate was significantly higher in patients who underwent both phacoemulsification and vitreoretinal surgeries than in group 2 (p < 0.05). In group 1, complications developed during surgery in the other eye in 28.1% of the patients whose permanent legal blindness stemmed from a complication in the previous surgery. In contrast, complications arose in the surgery of the other eye in 10% of patients whose permanent legal blindness did not result from any complications in the previous surgery. A statistically significant difference was observed between the two groups (P < 0.05).<br><br>DISCUSSION: In our study, if the cause of eye loss in patients with permanent legal blindness in one eye was a surgical complication, the possibility of complications during surgery in the other eye was high. Surgery can be planned at higher visual acuity levels in a patient who has lost one eye for reasons other than surgery. In patients who have lost one eye due to previous surgery, surgery for the other can be planned at lower visual acuity levels.<br><br>CONCLUSION: This is the first report to compare the rate of complications during and after surgery in patients with pre-existing permanent legal blindness in one eye who underwent cataract surgery and vitreoretinal surgery in the other.},
}
@article {pmid39935708,
year = {2024},
author = {Schoumacher, M and Lambert, V and Campas, M and Blaise, P and Locht, B and Thys, M and Duchateau, E and Cavalier, E and Rakic, JM and Noël, A and de Tullio, P},
title = {Opportunities, challenges, and difficulties in NMR-based metabolomics applied to neovascular age-related macular degeneration (nAMD) patient follow-up.},
journal = {Frontiers in molecular biosciences},
volume = {11},
number = {},
pages = {1449226},
pmid = {39935708},
issn = {2296-889X},
abstract = {INTRODUCTION: This study applies NMR-based metabolomics to investigate neovascular age-related macular degeneration (nAMD), addressing challenges in patient management, disease progression evaluation, and treatment response assessment. A two-year follow-up of 29 nAMD patients undergoing treatment provided 231 time points for analysis.<br><br>METHODS: Over the two-year period, 11 males and 18 females (aged 61-92 years) were monitored, yielding 231 time points. At each time point, blood samples for NMR metabolomics analysis, clinical measurements (e.g., lactate, glucose levels, HDL/LDL cholesterol, and blood pH), and optical coherence tomography (OCT) images were collected to evaluate the progression of choroidal neovascularization. 1H-NMR metabolomic analysis led to the quantification of over 60 metabolites and of the major lipoprotein fractions. Both multivariate and univariate statistical approaches tailored for longitudinal data were employed to identify biomarkers correlating metabolomic changes with ocular alterations during disease progression.<br><br>RESULTS AND DISCUSSION: Despite a rigorous analytical workflow enabling precise quantification of over 60 metabolites and the application of advanced statistical tools for longitudinal data, achieving consistent results across the cohort proved challenging. The dataset's heterogeneity, reflecting real-world clinical practice, complicated the derivation of global conclusions. Personalized analyses on a patient-by-patient basis successfully identified individual correlation models, but a universal model remained elusive. This study highlights the inherent challenges of translating findings from controlled settings into clinical practice, where factors such as visit frequency, treatment variability, and disease heterogeneity limit data uniformity. We emphasize the importance of experimental design in longitudinal studies, particularly when dealing with incomplete and variable datasets. We are therefore confident that, considering both the challenges and difficulties identified in this work and the preliminary results presented here, it is possible to develop predictive and individualized models for monitoring patients with nAMD. Such models could greatly assist clinicians in providing better care for these patients.},
}
@article {pmid39934587,
year = {2025},
author = {Sabado, RRS and Corpus-Velasquez, K and Aguilar, RN},
title = {Practice patterns and preferences in the management of age-related macular degeneration among vitreoretinal surgeons in the Philippines.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {71},
pmid = {39934587},
issn = {1573-2630},
mesh = {Humans ; Philippines/epidemiology ; Cross-Sectional Studies ; *Practice Patterns, Physicians'/statistics &amp; numerical data ; Female ; Male ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Macular Degeneration/therapy/epidemiology ; *Vitreoretinal Surgery ; Middle Aged ; Surveys and Questionnaires ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Disease Management ; Surgeons ; },
abstract = {PURPOSE: To determine the practice patterns and preferences in the management of age-related macular degeneration (AMD) among vitreoretinal surgeons in the Philippines.<br><br>METHODS: This is a descriptive cross-sectional study. A validated online survey regarding practices in AMD management was sent to the members of the Vitreo-Retina Society of the Philippines (VRSP). Data were analyzed using frequency and percent distributions.<br><br>RESULTS: A total of 114 vitreoretinal surgeons participated in the study. Majority (97.4%) inquired about patients' smoking habits and advised cessation (99.1%). Dietary advice (94.7%) focused on omega-3-rich foods and green, leafy vegetables. Oral antioxidant supplements were prescribed for unilateral intermediate AMD (83.3%), with the age-related eye disease studies formula most commonly used (25.7%). Anti-vascular endothelial growth factor (anti-VEGF) was preferred for subfoveal (99.1%), juxtafoveal (94.7%), and extrafoveal (73.5%) choroidal neovascularization, with bevacizumab being the most frequently administered agent (72.6%) and aflibercept (83.2%) the most preferred due to cost considerations. The treat-and-extend protocol was followed by 58.4%, while 38.9% used a pro re nata approach. Treatment response was primarily evaluated by fluid reduction on optical coherence tomography, with intraretinal fluid being the most critical (48.7%). Most surgeons (86.7%) switched anti-VEGF agents for poor response, and 80.5% did so when no response was seen. Referral to low vision specialists was most often based on difficulty performing daily activities regardless of visual acuity.<br><br>CONCLUSION: Real-world practice patterns and preferences of the members of the VRSP generally align with globally recognized management standards for AMD. They displayed remarkable knowledge and attitudes with regards to smoking, diet, and nutrition in relation to AMD care. Anti-VEGF drugs have been used widely for neovascular AMD in accordance with international guidelines. A significant proportion acknowledge the advantages of referral to a low vision specialist.},
}
@article {pmid39934449,
year = {2025},
author = {Kusumanchi, P and Madsen, JG and Bek, T and Keller, SS and Davidsen, RS},
title = {Electrical stimulation of neuroretinas with 3D pyrolytic carbon electrodes.},
journal = {Biomedical microdevices},
volume = {27},
number = {1},
pages = {7},
pmid = {39934449},
issn = {1572-8781},
support = {NNF20OC0064628//Novo Nordisk Fonden/ ; R303-2018-2898//Lundbeck Fonden/ ; },
mesh = {Animals ; *Electric Stimulation/instrumentation ; *Carbon/chemistry ; Action Potentials/drug effects ; Swine ; *Retina/physiology/cytology ; Electrodes ; },
abstract = {Retinal prosthesis has been one of the medical strategies aimed at restoring some degree of vision for patients affected by retinal degenerative diseases, such as Retinitis Pigmentosa (RP) and age-related macular degeneration (AMD), which are leading causes of irreversible visual loss. In retinal prosthesis, electrical pulses are typically delivered to the retinal neurons via electrodes on the surface of the implant. In this work, we fabricated 3D carbon pillar electrodes by pyrolysis of SU-8 structures defined photolithographically on Si wafers. We then measured compound action potentials induced in porcine neuroretinas stimulated with electrical pulses. The recorded spikes were validated to be biological in origin by adding the voltage-gated sodium-channel blocking agent tetrodotoxin. The minimum threshold voltage needed to effectively stimulate retinal cells, such as retinal ganglion cells, with 3D electrodes was analyzed through systematic investigation of the spike rate and amplitudes as a function of stimulation voltage. 3D electrodes significantly increased spike rate and amplitudes above spontaneous activity in the tissue during stimulation and outperformed the 2D counterpart, both in terms of spike rate and amplitude. Our results indicate a threshold voltage range of 500-600 mV for 1 ms pulses at a frequency of 10 Hz above which a significant increase in spike count was observed. Furthermore, we report an order of magnitude increase in peak-to-peak amplitude for evoked spikes (> 3 mV), compared to spontaneous spikes (∼ 200 µV). Based on numerical integration, we estimate the area under the curve to be ~14 times larger in evoked compound action potentials compared to spontaneous activity. This indicates the relative increase in number of contributing cells to the compound action potential. At a stimulation voltage of 600 mV the spike rate for 3D electrodes was above 10 spikes/channel/s. We hypothesize that the significant difference between 2D and 3D electrodes is not only caused by the higher active electrode surface area of the 3D micropillar electrodes, but also by more intricate contact and interaction with the inner cell layers of the retinal tissue. Our findings indicate that 3D carbon micropillar electrodes are promising for electrical stimulation of the retina.},
}
@article {pmid39934192,
year = {2025},
author = {Kansal, I and Khullar, V and Sharma, P and Singh, S and Hamid, JA and Santhosh, AJ},
title = {Multiple model visual feature embedding and selection method for an efficient oncular disease classification.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {5157},
pmid = {39934192},
issn = {2045-2322},
mesh = {Humans ; Neural Networks, Computer ; Deep Learning ; *Eye Diseases/classification/diagnosis/diagnostic imaging ; Algorithms ; },
abstract = {Early detection of ocular diseases is vital to preventing severe complications, yet it remains challenging due to the need for skilled specialists, complex imaging processes, and limited resources. Automated solutions are essential to enhance diagnostic precision and support clinical workflows. This study presents a deep learning-based system for automated classification of ocular diseases using the Ocular Disease Intelligent Recognition (ODIR) dataset. The dataset includes 5,000 patient fundus images labeled into eight categories of ocular diseases. Initial experiments utilized transfer learning models such as DenseNet201, EfficientNetB3, and InceptionResNetV2. To optimize computational efficiency, a novel two-level feature selection framework combining Linear Discriminant Analysis (LDA) and advanced neural network classifiers-Deep Neural Networks (DNN), Long Short-Term Memory (LSTM), and Bidirectional LSTM (BiLSTM)-was introduced. Among the tested approaches, the "Combined Data" strategy utilizing features from all three models achieved the best results, with the BiLSTM classifier attaining 100% accuracy, precision, and recall on the training set, and over 98% performance on the validation set. The LDA-based framework significantly reduced computational complexity while enhancing classification accuracy. The proposed system demonstrates a scalable, efficient solution for ocular disease detection, offering robust support for clinical decision-making. By bridging the gap between clinical demands and technological capabilities, it has the potential to alleviate the workload of ophthalmologists, particularly in resource-constrained settings, and improve patient outcomes globally.},
}
@article {pmid39933144,
year = {2025},
author = {Vasavada, S and Shastri, L and Nath, V and Dwivedi, S and Patel, A and Vasavada, V and Srivastava, S and Vasavada, AR},
title = {Visual outcomes after implantation of a nondiffractive EDOF intraocular lens in patients with early dry macular degeneration.},
journal = {Journal of cataract and refractive surgery},
volume = {51},
number = {6},
pages = {456-460},
doi = {10.1097/j.jcrs.0000000000001627},
pmid = {39933144},
issn = {1873-4502},
mesh = {Humans ; *Visual Acuity/physiology ; Prospective Studies ; Aged ; *Lens Implantation, Intraocular ; Male ; Female ; Contrast Sensitivity/physiology ; *Lenses, Intraocular ; *Phacoemulsification ; *Pseudophakia/physiopathology ; Middle Aged ; *Geographic Atrophy/physiopathology/surgery/complications ; *Depth Perception/physiology ; Prosthesis Design ; Treatment Outcome ; },
abstract = {PURPOSE: To evaluate visual outcomes after implantation of a nondiffractive extended depth-of-focus (EDOF) intraocular lens (IOL) in patients with early age-related dry macular degeneration (AMD).<br><br>SETTING: Iladevi Cataract &amp; IOL Research Centre, Ahmedabad, India.<br><br>DESIGN: Prospective, interventional series.<br><br>METHODS: Patients undergoing cataract surgery with the EDOF AcrySof Vivity IOL and having early dry AMD were included. Primary outcome measures were monocular unaided and corrected distance visual acuity (UDVA, CDVA) 3 months postoperatively. Secondary outcome measures were monocular unaided and distance-corrected intermediate (UIVA, DCIVA) (66 cm) and near (UNVA, DCNVA) (40 cm) visual acuity as well as mesopic contrast sensitivity (CS).<br><br>RESULTS: 40 eyes (40 patients) with a mean age of 68.5 &#xb1; 8.38 (SD) years were included. UDVA and CDVA at 3-month follow-up were 0.12 &#xb1; 0.07 and 0.10 &#xb1; 0.10 (SD) logMAR. UIVA and DCIVA were 0.25 &#xb1; 0.09 and 0.12 &#xb1; 0.09 logMAR. UNVA and DCNVA were 0.23 &#xb1; 0.10 and 0.19 &#xb1; 0.15 logMAR. Mesopic CS values without glare were 1.50 &#xb1; 0.10, 1.69 &#xb1; 0.26, 1.40 &#xb1; 0.30, and 0.84 &#xb1; 0.5 units at 3, 6, 12, and 18 cycles per degree. Mesopic CS with glare was 1.53 &#xb1; 0.16, 1.63 &#xb1; 0.21, 1.21 &#xb1; 0.45, and 0.75 &#xb1; 0.42 units.<br><br>CONCLUSIONS: The AcrySof Vivity IOL gave very good distance visual acuity with improved intermediate and near visual acuity without significant compromise in CS in eyes with early dry AMD.},
}
@article {pmid39931677,
year = {2025},
author = {Barakat, MR and Kwong, HM and Marcon, G and O'Leary, OE and Paris, LP and Schneider, P and Tang, Y and Graff, JM},
title = {Human Factors Studies to Assess the Usability of the Faricimab Prefilled Syringe.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {395-406},
pmid = {39931677},
issn = {1177-5467},
abstract = {PURPOSE: Faricimab, the first bispecific antibody designed for intraocular use, is approved for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Here, we report the usability of a novel faricimab 6 mg pre-filled syringe (PFS) configuration that has been designed specifically for intravitreal use.<br><br>PATIENTS AND METHODS: A simulated-use human factors validation study enrolling 15 retina specialists and 15 ophthalmic assistants was conducted in a market research facility configured to represent an ophthalmology clinic. Participants' ability to complete tasks related to package handling, dose preparation, and injection of a faricimab 6 mg dose into a polymer eye using the PFS was assessed. In a second Phase 3b, single-arm, actual-use study, the ability of seven retina specialists and six ophthalmic assistants to prepare and administer the PFS in accordance with the instructions for use was assessed. Injections were performed into single eyes of 35 patients with nAMD or DME in three US clinics and patients were followed for 7 days for safety reporting (ClinicalTrials.gov identifier: NCT05569148).<br><br>RESULTS: In the simulated-use study, most retina specialists and ophthalmic assistants completed all tasks deemed essential for PFS preparation and administration correctly and without error. Of the 22 tasks, the pass rate was 86.7-100%; 16 tasks had a pass rate of 100%. No use errors were observed during the actual-use study. One patient experienced one mild adverse event of eye irritation that resolved the same day and was deemed unrelated to the study drug.<br><br>CONCLUSION: Participants were able to safely and correctly prepare and administer a faricimab 6 mg dose using the PFS in accordance with the instructions for use, under realistic conditions representing the real world. The faricimab 6 mg PFS may therefore offer a more convenient, safe-handling alternative to vial administration.},
}
@article {pmid39930486,
year = {2025},
author = {Abe, M and Kunikata, H and Aizawa, N and Yasuda, M and Nitta, F and Abe, T and Nakazawa, T},
title = {Systemic oxidative stress levels and their associations with the risk of neovascular age-related macular degeneration and treatment response.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {16},
pmid = {39930486},
issn = {2056-9920},
support = {Scientific Research (C) H.K. 17K11445 and M.Y. 23K09055//JSPS KAKENHI Grants-in-Aid/ ; Scientific Research (C) H.K. 17K11445 and M.Y. 23K09055//JSPS KAKENHI Grants-in-Aid/ ; COI-NEXT (JPMJPF2201)//JST grants/ ; },
abstract = {PURPOSE: To investigate the association between oxidative stress (OS) and both the risk of neovascular age-related macular degeneration (nAMD) and the treatment response to intravitreal anti-vascular endothelial growth factor injections (anti-VEGF IVIs).<br><br>METHODS: This retrospective study included 46 treatment-na&#xef;ve nAMD eyes of 46 patients (26 male and 20 female) who received anti-VEGF IVIs with a "treat-and-extend" regimen&#xa0;following an initial loading phase for one&#xa0;year. The patients were divided into two groups according to the total number of anti-VEGF IVIs administered during the year: the "effective" group and the "resistant" group. OS was evaluated by diacron reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and skin autofluorescence (SAF) at baseline. For comparison, 54 control subjects were recruited.<br><br>RESULTS: There were&#xa0;no significant differences in d-ROM&#xa0;or BAP levels&#xa0;between control subjects&#xa0;and nAMD patients,&#xa0;regardless of sex,&#xa0;whereas&#xa0;SAF levels were higher in nAMD patients overall and in male nAMD patients than in controls&#xa0;(P&#x2009;< 0.001 for both).&#xa0;The effective and resistant groups included 30 and 16 eyes, respectively. Among the male nAMD&#xa0;patients, the effective and resistant groups had similar baseline characteristics, including age, smoking history, visual acuity, and&#xa0;central macular thickness;&#xa0;however, the resistant group had higher SAF levels&#xa0;(effective vs. resistant: 2.3 vs. 2.6 arbitrary units [AU]; P&#x2009;=&#x2009;0.02). This finding was further supported by a multiple logistic regression analysis, which showed that&#xa0;the&#xa0;odds ratio for SAF&#xa0;was 1.57 per 0.1 AU increase (P&#x2009;=&#x2009;0.01).<br><br>CONCLUSION: SAF levels were significantly higher&#xa0;in nAMD patients than in controls. The total number of anti-VEGF IVIs required&#xa0;over one year in male nAMD patients depended on SAF levels, suggesting that&#xa0;the SAF levels may serve as a potential biomarker for the response to anti-VEGF IVIs in nAMD.},
}
@article {pmid39930367,
year = {2025},
author = {Fitton, CA and Quigley, MMR and Belch, JJF},
title = {Risk factors for wet macular degeneration: a systematic review, with novel insights from the Scottish Heart Health Extended Cohort.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {67},
pmid = {39930367},
issn = {1471-2415},
mesh = {Humans ; Risk Factors ; *Wet Macular Degeneration/epidemiology/etiology ; Scotland/epidemiology ; Male ; Aged ; Female ; Middle Aged ; Incidence ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a major cause of vision loss worldwide. This study aimed to assess risk factors for wet AMD by two methods: assessing risk factors measured in the Scottish Heart Health Extended Cohort (SHHEC), and to systematically review the literature.<br><br>METHODS: Eighteen thousand one hundred seven volunteers were recruited to SHHEC between 1984-1995, with risk factor data collected on recruitment. Hospital records were linked to study data up to 2017 and survival analysis was used to analyse risk factors and wet AMD. Literature published between 2000-2023 was searched for studies assessing risk factors for wet AMD, resulting in 5,503 papers. Following review, 7 studies were included in the systematic review.<br><br>RESULTS: Within the SHHEC data, 231 cases of wet AMD were reported. Increasing age (Hazard Ratio (HR) 10.51; 99% Confidence Interval (CI) 4.78-23.11) and smoking (HR 1.67; 99% CI 1.17-2.38) were significantly associated with an increased risk of wet AMD. Increased dietary intake of vitamin K (HR 0.56; 99% CI 0.34-0.94) was associated with a decreased risk of wet AMD. According to a systematic review, smoking, high Body mass index, heavy alcohol intake, increased systolic blood pressure, increased pulse pressure, and high levels of C-reactive protein and serum triglycerides in the blood may be associated with an increased risk of wet AMD. However, the studies provide mixed evidence and no conclusive results.<br><br>CONCLUSION: We have demonstrated that increasing age and smoking are high-risk factors for the development of wet AMD, while vitamin K is associated with a reduced risk of wet AMD.},
}
@article {pmid39930245,
year = {2025},
author = {Grossman, GH and Cattell, T and Abbott, A and MacIntyre, D},
title = {Artificial Intelligence-Assisted Matching of Human Postmortem Donors to Ocular Research Projects.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {505-509},
pmid = {39930245},
issn = {0065-2598},
mesh = {Humans ; *Artificial Intelligence ; *Tissue Donors ; Retrospective Studies ; *Eye Banks ; Natural Language Processing ; *Biomedical Research/methods ; Databases, Factual ; Autopsy ; },
abstract = {The scarcity of human ocular samples with short postmortem intervals (PMIs) is a significant issue in ophthalmic research and drug discovery. A contributing factor is that eye banks must manually match donor data to prospective research project criteria, which is time-consuming, inefficient, and error-prone. We have previously reported on the successful use of a semi-automated matching system, ReSync. The barrier to full autonomy is that donor medical data is often provided as unstructured data in free text fields, which prevents interoperability with matching databases. Herein, we report on a small retrospective study, in which artificial intelligence (AI) is incorporated into ReSync (ReSyncAI) to test AI's ability to structure donor data for subsequent matching. From a set of historical cases, medical data was securely sent to a large language model with natural language processing. After structuring and standardizing, data was returned to ReSync for analysis and match testing. A 94.2% success rate in medical terminology keyword extraction in concert with correcting and standardizing medical data was achieved. Structured data was fully interoperable with ReSync. In a subset of cases, ReSyncAI properly matched donors to the standardized term of "age-related macular degeneration" from donor data, including instances of abbreviations, misspellings, and incomplete designations.},
}
@article {pmid39930244,
year = {2025},
author = {Toto, R and Soltau, CP and Rayner, CL and Bottle, SE and Barnett, NL},
title = {Steroid-Nitroxide Hybrid Compound Protects the Retina in a Model of CNV.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {497-501},
pmid = {39930244},
issn = {0065-2598},
mesh = {Animals ; Rats ; *Retina/drug effects/pathology ; *Choroidal Neovascularization/pathology/drug therapy/prevention &amp; control ; *Cyclic N-Oxides/pharmacology/chemistry ; Disease Models, Animal ; *Prednisolone/pharmacology/analogs &amp; derivatives ; *Antioxidants/pharmacology ; Oxidative Stress/drug effects ; Male ; *Nitrogen Oxides/pharmacology/chemistry ; },
abstract = {Nitroxide-based drugs have proven effective in modulating radical-induced oxidative stress by modulating antioxidant enzymes and genes that control distinct immune and anti-inflammatory responses. Due to their reasonable chemical stability and ability to shuttle between oxidized and reduced forms at physiologically relevant redox potentials, nitroxide-based radicals have also proven effective as biological probes of redox status. Herein, we investigated the potential of a unique nitroxide-based antioxidant and anti-inflammatory agent to protect the retina from experimentally induced degeneration. An established rat model of retinal degeneration was used viz. laser-induced choroidal neovascularization (CNV) to study the effects of the hybrid steroidal anti-inflammatory-antioxidant prednisolone 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) nitroxide compound. Vascular endothelial cell distribution at the CNV lesion site was investigated using isolectin B4 fluorescence histology, and the inflammatory response of microglia was investigated using IBA-1 immunohistochemistry. The prednisolone-TEMPO (Pred-TEMPO) hybrid reduced the laser-induced CNV lesion area compared to untreated control rats. These findings demonstrate that nitroxide-based compounds are potential therapeutics for retinal degenerative diseases involving inflammatory and oxidative stress-mediated components, including age-related macular degeneration.},
}
@article {pmid39930243,
year = {2025},
author = {O'Brien, J and Colucci, P and Alvarez, Y and Kennedy, BN},
title = {Uncovering Novel Drugs that Restore Vision Using Orthogonal Pooling in Zebrafish.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {491-495},
pmid = {39930243},
issn = {0065-2598},
mesh = {Animals ; Zebrafish/genetics ; Disease Models, Animal ; *Vision, Ocular/drug effects ; Animals, Genetically Modified ; Humans ; *Retinal Degeneration/drug therapy/genetics ; *Drug Discovery/methods ; Drug Evaluation, Preclinical/methods ; Zebrafish Proteins/genetics ; Nystagmus, Optokinetic/drug effects ; },
abstract = {Photoreceptor and retinal pigment epithelium (RPE) dysfunction in inherited retinal degenerations (IRDs) and age-related macular degeneration (AMD) necessitate innovative therapies to preserve vision. Vision impairment incurs a substantial global economic burden, with the World Health Organization reporting an annual global productivity loss of approximately $411 billion. Current treatments are limited, underscoring the urgency for novel solutions. Leveraging new screening techniques, novel drugs restoring vision can be uncovered. Here, a workflow is described utilising orthogonal pooling to screen randomised library compounds for drug hits restoring vision and assessing the optokinetic response (OKR) in the atp6v0e1[-/-] zebrafish model of inherited blindness.},
}
@article {pmid39930239,
year = {2025},
author = {Wögenstein, GM and Grimm, C},
title = {Genetically Encoded Metabolic Sensors to Study Retina Metabolism.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {465-469},
pmid = {39930239},
issn = {0065-2598},
mesh = {Humans ; Animals ; *Retina/metabolism ; Retinal Pigment Epithelium/metabolism ; Luminescent Proteins/genetics/metabolism ; },
abstract = {Dysfunctional retinal metabolism has been shown to contribute to retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration (IRD). Data indicates that metabolism in the retina is complex and involves intricate interactions between cell types, including the exchange of metabolites between photoreceptors and retinal pigment epithelium (RPE) cells. To understand these interactions on a single cell level, cell-type specific expression of genetically encoded metabolic sensors can be used to reach a spatial and temporal resolution that is superior to other techniques. These sensors comprise a metabolite binding site and a fluorescent reporter protein. The binding of the metabolite leads to changes in the emission of the fluorophore which can be detected by specialized microscopy. The usage of such sensors together with other techniques in the normal and diseased retina will not only help to resolve metabolic interactions between cells and fluxes of metabolites but also enhance our understanding of pathophysiological changes in the retina.},
}
@article {pmid39930236,
year = {2025},
author = {Hashimoto, Y and Campbell, M},
title = {Key Claudins at the Blood-Retina Barriers.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {447-451},
pmid = {39930236},
issn = {0065-2598},
mesh = {Humans ; *Blood-Retinal Barrier/metabolism/pathology ; *Tight Junctions/metabolism/pathology ; *Claudins/metabolism/genetics ; Animals ; *Diabetic Retinopathy/metabolism/pathology/genetics ; *Macular Degeneration/metabolism/pathology/genetics ; *Claudin-5/metabolism/genetics ; Retinal Pigment Epithelium/metabolism/pathology ; Endothelial Cells/metabolism/pathology ; },
abstract = {Tight junctions are physical barriers that limit the paracellular diffusion of solutes and ions. The blood-retina barriers are cellular barriers composed of tight junctions established in retinal pigment epithelial (RPE) cells and retinal endothelial cells to maintain retinal homeostasis. Claudins are the major components of tight junctions, and their dysregulation leads to impaired blood-retina barrier integrity, resulting in retinal diseases with concomitant local inflammation. In this chapter, we introduce two important claudins, claudin-5 and -19, and briefly explain how decreased expression of these claudins is associated with the progress of diabetic retinopathy (DR) and age-related macular degeneration (AMD) by compromising the blood-retina barriers.},
}
@article {pmid39930234,
year = {2025},
author = {Lim, RR and Chao, JR},
title = {Ocular Localization of Complement Factor H and Its Association with Diseases in the Eye.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {435-439},
pmid = {39930234},
issn = {0065-2598},
mesh = {Humans ; *Complement Factor H/genetics/metabolism/immunology ; *Eye Diseases/metabolism/immunology/genetics/pathology ; *Eye/metabolism/immunology/pathology ; Complement Activation ; Animals ; },
abstract = {The complement system is a well-documented element of the immune system that protects the body from external pathogens. Although the majority of complement components are produced by the liver and secreted into the circulation, ocular tissues also produce several complement components, thereby contributing to local complement activity in specific regions of the eye. Regulation of complement cascade activation is crucial for preventing unintended cellular damage. In the alternative pathway of the complement system, complement factor H (CFH) plays an important role in inhibitory regulation. Certain genetic polymorphisms that result in defective CFH are associated with rare diseases where the self is attacked by an overactive complement system. This review will focus on the expression and localization of CFH in human ocular tissues and highlight its association with several diseases in the anterior and posterior chambers of the eye.},
}
@article {pmid39930227,
year = {2025},
author = {Burton, EL and Tovell, VE and Coffey, P},
title = {Importance of Choriocapillaris Replacement in Therapeutic Strategies for Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {389-393},
pmid = {39930227},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/therapy/pathology/physiopathology ; *Choroid/pathology/blood supply ; *Retinal Pigment Epithelium/pathology ; Animals ; Pericytes/transplantation/pathology ; *Cell- and Tissue-Based Therapy/methods ; Tissue Engineering/methods ; },
abstract = {Age-related macular degeneration (AMD) is a progressive disease of the retina, characterised by the degeneration of several cell layers, including the choriocapillaris (CC), retinal pigment epithelium (RPE) and photoreceptors (PR). Because of this, cell replacement therapies have the potential to treat AMD. Previous research has predominantly focussed on the development of a transplantable pluripotent stem cell-derived RPE monolayer, owing to RPE degeneration early in AMD. However, there is now increasing evidence for CC atrophy early in the pathogenesis of AMD. Given the crucial role of the CC in retinal homeostasis, there is significant potential to expand research into CC replacement with the hope of advancing current cell therapies. The RPE and CC have a highly interconnected relationship, and thus, the replacement of one of these cell layers while the other remains dysfunctional may not be optimal for the long-term rescue of vision in AMD. Therefore, one approach would be to replace both the RPE and CC as a combined cell therapy. Here, we outline the importance of CC in health and disease, as well as potential considerations when building a tissue-engineered CC-like vascular network, with a particular focus on pericytes.},
}
@article {pmid39930225,
year = {2025},
author = {Ridley, RB and Amontree, AC and Lewin, AS and Ildefonso, CJ},
title = {Mitochondrial DNA Damage in the Retinal Pigmented Epithelium (RPE) and Its Role in RPE Pathobiology.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {375-379},
pmid = {39930225},
issn = {0065-2598},
support = {S10 OD028476/OD/NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/metabolism ; *DNA, Mitochondrial/genetics/metabolism ; *DNA Damage ; *Mitochondria/pathology/genetics/metabolism ; Animals ; *Macular Degeneration/genetics/pathology/metabolism ; },
abstract = {Retinal pigmented epithelial (RPE) cells have critical functions in the retina. These cells rely heavily on their mitochondria to generate energy, offer metabolites for biosynthesis through the TCA cycle, regulate apoptosis, and process lipids from photoreceptors. Therefore, mitochondrial damage has significant consequences for the RPE and, by proxy, photoreceptors. Researchers have identified damaged mitochondrial DNA (mtDNA) accumulation in patient samples from aged and diseased individuals. These damages include point mutations and complete deletions of mtDNA segments. The most significant observation in these studies is a positive correlation between the accumulation of damaged mtDNA with the stage of AMD rather than aging. This chapter will discuss how mitochondrial dysfunction in the RPE can drive disease pathobiology by altering their physiological functions.},
}
@article {pmid39930224,
year = {2025},
author = {Sekulic, A and Wildner, G and Skerka, C and Strauß, O},
title = {Immunogenic Switch of RPE Cells.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {369-373},
pmid = {39930224},
issn = {0065-2598},
mesh = {*Retinal Pigment Epithelium/immunology/pathology/metabolism ; Humans ; Animals ; *Macular Degeneration/immunology/pathology ; Forkhead Transcription Factors/immunology/metabolism/genetics ; Mice ; },
abstract = {The barrier function of the retinal pigment epithelium (RPE) secures a highly selective exchange of molecules between the blood stream of the choroid and retina but also maintenance of the immune privilege of the retina. The latter function includes a mechanical barrier through the tight junctions and immune barrier of either membrane bound or secreted immune-suppressive factors in response to increasing inflammatory activities in the outer retina. However, in disease, both physical and immune barriers are compromised to allow accumulation of immune cells in the subretinal space or even to pass across the RPE into the retinal space. The ability of the RPE to secrete immune stimulatory factors such as MCP-1, as a response to the increased inflammation, suggests that disease goes along with an immunogenic switch. We recently found that stressed RPE cells express the transcription factor FoxP3 and its activation leads to secretion of pro-inflammatory factors. Indeed, RPE cells in either mouse models with age-related macular degeneration (AMD) relevance or in retinas from AMD patients, express FoxP3 in the RPE, which was not observed in healthy donors. FoxP3 appears first as a rescue factor for the RPE in the increasing presence of pro-inflammatory proteins such as IL1β or active complement that eventually changes the immunogenic phenotype from anti-inflammatory to pro-inflammatory.},
}
@article {pmid39930220,
year = {2025},
author = {Armento, A and Almansa-Garcia, AC and Sen, M and Merle, DA and Arango-Gonzalez, B and Ueffing, M},
title = {Signaling Pathways in Retinal Pigment Epithelium (RPE) Cells in Response to Stress Conditions of Age-Related Macular Degeneration (AMD).},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {345-349},
pmid = {39930220},
issn = {0065-2598},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/metabolism/pathology/genetics ; *Signal Transduction ; Animals ; *Oxidative Stress ; },
abstract = {Age-related macular degeneration (AMD), affecting circa 200 million people worldwide, is a debilitating disease leading to visual loss in the elderly population. The main risk for AMD is advanced age. Genetic predisposition as well as modern lifestyle habits, such as smoking or unhealthy diets, increase this risk. On the molecular level, these risks convert into complex systemic changes at the interface of the choriocapillaris, Bruch's membrane, RPE, and neuroretina, affecting the functional integrity and survival of RPE and photoreceptors cells. To date, therapeutic options for AMD patients are limited. Pathway identification and a detailed understanding of the molecular mechanisms driving AMD are prerequisites to defining potential novel druggable targets. This review aims to give a short overview of the known cell signaling pathways focusing on RPE cells in response to stress conditions occurring in AMD.},
}
@article {pmid39930219,
year = {2025},
author = {Klingeborn, M and Reese, ED},
title = {Desmosome and Hemidesmosome Disassembly in Retinal Pigmented Epithelium: Intersection with the Exosome Pathway.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {339-343},
pmid = {39930219},
issn = {0065-2598},
mesh = {*Exosomes/metabolism/pathology ; Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Desmosomes/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; Animals ; *Hemidesmosomes/metabolism/pathology ; Signal Transduction ; Biomarkers/metabolism ; Oxidative Stress ; },
abstract = {The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, and like other epithelia it has several different types of cell-cell junctions, such as desmosomes. The RPE provides key metabolic and nutrient support to photoreceptors and the function of normal vision. The RPE is a principal location of disease-associated changes in age-related macular degeneration (AMD), due to its essential role in visual homeostasis. There are no robust early indicators of AMD or disease progression, a need that could be filled by the development of early AMD biomarkers. Exosomes are lipid bilayer membrane vesicles of nanometer sizes that are released via a dedicated machinery by all cells and carry out a multitude of functions related to cellular signaling and waste management. In the RPE, they are released from both the apical and basal sides, and the cargo composition reflects this polarization. We have recently shown that exosomes released from the basolateral side of RPE cells under chronic oxidative stress conditions contain desmosome and hemidesmosome proteins. Here we discuss the composition of desmosomes and hemidesmosomes in the RPE, and the potential of these exosome-associated components as biomarkers of early RPE dysfunction preceding AMD symptoms detectable in the current clinical setting. How cargo loading into basolateral exosomes is controlled in polarized epithelia such as RPE, is also discussed.},
}
@article {pmid39930207,
year = {2025},
author = {Govers, LP and Grimm, C},
title = {The Connection Between Cellular Metabolism and Retinal Disease.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {267-271},
pmid = {39930207},
issn = {0065-2598},
mesh = {Humans ; *Retinal Diseases/metabolism/genetics/pathology ; *Retina/metabolism/pathology ; Animals ; Metabolic Networks and Pathways/genetics ; Metabolomics ; },
abstract = {The retina is one of the most metabolically active tissues in the human body and has its own complex metabolic environment as the different cell types in this tissue are interconnected to maintain a healthy retinal homeostasis. Any disturbances in the homeostatic balance may have a severe impact on retinal function affecting vision. About 341 genes are listed in the RetNet database as being causative for monogenic inherited retinal diseases. By intersecting this list with the Mammalian Metabolic Enzyme Database, we identified 28 metabolic genes that can result in diseases such as retinitis pigmentosa, Leber congenital amaurosis, or optic atrophy when mutated. Alongside inherited retinal diseases, metabolism also plays a prominent role in acquired retinal diseases. Metabolomics studies have been performed on patients with age-related macular degeneration, diabetic retinopathy, and glaucoma revealing dysregulated metabolic pathways, such as lipid, amino acid, and purine metabolism, in the onset of disease. Although there are distinct pathophysiological differences between inherited and acquired retinal disorders, diving deeper into the role of metabolism and how metabolic dysfunction may overlap with different pathologies, could give us indications on how to design approaches to normalize the homeostatic balance in the retina as treatment options to protect vision.},
}
@article {pmid39930200,
year = {2025},
author = {Noel, NCL},
title = {Fish Models of Ageing Retinal Disease.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {225-228},
pmid = {39930200},
issn = {0065-2598},
mesh = {Animals ; *Disease Models, Animal ; *Aging/pathology/physiology ; Zebrafish ; Retina/pathology ; Oryzias ; *Macular Degeneration/pathology/genetics/physiopathology ; *Retinal Diseases/pathology/physiopathology ; Humans ; *Fishes ; },
abstract = {Age-related macular degeneration (AMD) is a common cause of vision loss with few effective treatments available to prevent retinal degeneration long-term. Challenges associated with treatment development are due in part to a lack of understanding of the mechanisms underlying disease onset. However, diseases of ageing are challenging to model. Here, features of diurnal fish models that are beneficial for studying ageing retinal diseases are highlighted, and the unique characteristics of ageing zebrafish, turquoise killifish, and medaka retinas are summarised.},
}
@article {pmid39930199,
year = {2025},
author = {Lu, Q and Reynolds, AL},
title = {Proposing Zebrafish as a Model for Stargardt Disease.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {219-223},
pmid = {39930199},
issn = {0065-2598},
mesh = {Animals ; *Zebrafish/genetics ; *Stargardt Disease/genetics/pathology ; *Disease Models, Animal ; Humans ; ATP-Binding Cassette Transporters/genetics ; Mutation ; Retinal Cone Photoreceptor Cells/pathology/metabolism ; *Macular Degeneration/congenital/genetics/pathology ; },
abstract = {Stargardt disease (STGD1) is an inherited juvenile macular degeneration caused by mutations in the ATP-binding cassette subfamily A member 4 gene (ABCA4), a flippase located in the photoreceptor outer segment. ABCA4 mutations cause the buildup of a toxic byproduct in the retina called lipofuscin resulting in the death of photoreceptors by ferroptosis. Mammalian disease models (e.g., mouse Abca4[-/-]) have been established, but do not replicate all the disease symptoms in human STGD1 patients. It is challenging to model a cone degeneration disease like STGD1 using mice. Here we suggest zebrafish (Danio rerio) as a STGD1 model. This widely used vertebrate model organism is popular in the ocular field due to the early development of a cone-rich retina and the ability to correlate genotypes with relevant phenotypes. Zebrafish have been used to successfully model cone photoreceptor diseases including gene editing and drug-induced models. We propose zebrafish as a suitable diurnal model for STGD1.},
}
@article {pmid39930197,
year = {2025},
author = {Landowski, M and Ikeda, S and Ikeda, A},
title = {Association Between C22:5-Containing Lipids and RPE Pathologies in Mice with Tmem135 Overexpression.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {207-212},
pmid = {39930197},
issn = {0065-2598},
support = {F32 EY032766/EY/NEI NIH HHS/United States ; P30 EY016665/EY/NEI NIH HHS/United States ; R01 EY022086/EY/NEI NIH HHS/United States ; T32 EY027721/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Membrane Proteins/genetics/metabolism ; Mice ; *Macular Degeneration/pathology/metabolism/genetics ; Mice, Transgenic ; *Lipid Metabolism ; Disease Models, Animal ; *Lipids/blood ; Mice, Inbred C57BL ; },
abstract = {Dysregulation of lipid metabolism has been linked with risk for age-related retinal diseases including age-related macular degeneration (AMD). However, how dysregulated lipid metabolism contributes to AMD development is unknown. In this study, we evaluated the retinal and plasma lipidomes of a mouse model displaying retinal pigmented epithelium (RPE) pathologies that are observed in AMD including RPE dysmorphia and degeneration. We found that the RPE phenotypes in mice overexpressing transmembrane protein 135 (Tmem135 TG) are correlated with retinal and plasma lipidome changes. While distinct lipid profiles were observed in the retina and plasma of Tmem135 TG mice, a common finding in both retinal and plasma lipidomes was an increase of lipids containing C22:5. This data suggests that accumulation of C22:5-containing lipids may contribute to the development of the RPE pathologies in Tmem135 TG mice.},
}
@article {pmid39930190,
year = {2025},
author = {Parmar, T and Parmar, V and Malek, G},
title = {Potential Role of NUR77 in the Aging Retinal Pigment Epithelium and Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {165-169},
pmid = {39930190},
issn = {0065-2598},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/metabolism/pathology/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism/genetics ; Animals ; *Aging/metabolism/pathology ; Mice ; Mitochondria/metabolism/pathology ; },
abstract = {The underlying mechanisms associated with age-related changes in the morphology and function of retinal pigmented epithelial (RPE) cells are poorly understood. The aging RPE progresses through several structural changes including loss of melanin granules, accumulation of lipofuscin, and cytoskeletal changes, among others. Extracellular to it, there is also thickening of Bruch's membrane and changes in the integrity of the choroid. Recent studies have revealed that aging also affects the metabolic ecosystem of the RPE. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species generation, and increased number of mitochondrial mutations relative to baseline. These changes are also found in age-related macular degeneration (AMD), a late-onset vision-impairing disease, in which the RPE is particularly vulnerable. The orphan nuclear receptor NR4A1/NUR77 is an early response gene and regulator of various cellular processes during development, aging, and disease. Previously we observed decreased levels of Nur77/NUR77 in both mouse and human RPE as a function of age. Current knowledge of the function of this receptor in the RPE is limited. Herein, we discuss the putative roles of NUR77 in the RPE during aging and disease.},
}
@article {pmid39930185,
year = {2025},
author = {Ronning, KE and Burns, ME and Sennlaub, F},
title = {Monocytes in Retinal Degeneration: Little Cells with a Big Impact.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {133-137},
pmid = {39930185},
issn = {0065-2598},
mesh = {Humans ; *Monocytes/pathology/immunology/metabolism ; *Retinal Degeneration/pathology/immunology ; Animals ; *Retina/pathology/immunology ; Microglia/pathology/immunology ; Macular Degeneration/pathology/immunology ; },
abstract = {Inflammation has been strongly implicated in retinal degenerative disorders, including inherited retinal degenerations (IRDs) and age-related macular degeneration (AMD). Microglia are the only immune cells in the retina during normal function, but during damage and disease, monocytes are able to invade the retina. Despite similarities to microglia, monocyte-derived cells (MdCs) may play a distinct and often pathogenic role in disease. Recent technological advances are rapidly improving our ability to investigate monocytic cells, yet many questions remain. Still, it is clear monocytes play an important role during retinal degenerative disorders and they are an exciting target for the development of therapeutic interventions.},
}
@article {pmid39930184,
year = {2025},
author = {Dalton, R and Doyle, S},
title = {Current Perspectives of TLR2 Signalling in the Retina.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {127-131},
pmid = {39930184},
issn = {0065-2598},
mesh = {Humans ; *Toll-Like Receptor 2/metabolism/immunology/genetics/antagonists &amp; inhibitors ; *Signal Transduction ; *Retina/metabolism/immunology/pathology ; Animals ; Immunity, Innate ; *Macular Degeneration/immunology/metabolism/pathology ; *Diabetic Retinopathy/immunology/metabolism/pathology ; },
abstract = {Toll-like receptor 2 (TLR2) signalling is crucial in initiating the innate immune response. Under normal conditions, TLR2 can recognise and respond to danger signals in the body and protect against damaging pathogens and molecules. However, dysregulation of this tightly controlled cascade has been implicated in various retinal disorders. There are many endogenous sterile ligands present in a degenerating retina that could lead to aberrant TLR2 activation. This culminates in an overaction of the innate immune response, which leads to an excess of pro-inflammatory cytokine production and results in a dangerous cycle of chronic inflammation. Here, we will review the evidence behind TLR2's involvement in retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) and investigate the potential therapeutic benefit of TLR2 inhibition in the retina.},
}
@article {pmid39930169,
year = {2025},
author = {Wagh, V and Damodaren, N and Mittal, SK and Cardenas-Diaz, FL and Sun, H and Loktev, AV and Peterson, VM and Saini, JS},
title = {Cellular Senescence: An Emerging Player in the Pathogenesis of AMD.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {33-37},
pmid = {39930169},
issn = {0065-2598},
mesh = {Humans ; *Cellular Senescence ; *Macular Degeneration/pathology/metabolism ; *Retinal Pigment Epithelium/pathology/metabolism ; Animals ; Retinal Drusen/pathology/metabolism ; Bruch Membrane/pathology/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in the aged population. The accumulation of abnormal extracellular drusen deposits between the retinal pigment epithelium (RPE) and Bruch's membrane is a significant driver of AMD pathology. Drusen deposition leads to the degeneration of RPE cells and, subsequently, photoreceptors, driving the disease to its advanced stages and ultimately resulting in complete vision loss. Although the exact mechanisms underlying the AMD pathogenesis are not fully understood, it is hypothesized that the disease begins with the dysfunction of the RPE, triggering the complement and pro-inflammatory cascade. Over the last decade, new findings have implicated the involvement of cellular senescence (CS) in the pathology of age-related disorders. Specifically for AMD, evidence suggests that the senescence of RPE cells may play a role in the pathogenesis of the disease. In this review, we discuss the potential role of senescence in the onset and progression of AMD and propose potential therapeutic interventions that could be developed by targeting senescence.},
}
@article {pmid39930168,
year = {2025},
author = {Wubben, TJ and Weh, E and Besirli, CG},
title = {Photoreceptor Degeneration: More Than a Bystander in Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {27-31},
pmid = {39930168},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/pathology/metabolism/physiopathology ; *Retinal Pigment Epithelium/pathology/metabolism ; Animals ; *Photoreceptor Cells, Vertebrate/pathology/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment affecting nearly 200 million people worldwide, and this number is expected to increase in the coming decades. The role of the retinal pigment epithelium (RPE) in AMD pathogenesis has been extensively studied. However, the contribution of photoreceptor (PR) dysfunction to AMD pathogenesis remains understudied and is a critical gap in our knowledge. The RPE and PRs are coupled to promote and enhance their respective survival and function, and this delicate relationship becomes disrupted in AMD. Furthermore, PR metabolic demands are postulated to contribute to AMD pathogenesis, their dysfunction is associated with both the early and end stages of AMD, and their death is central to the vision loss patient's experience in AMD. Here, we review clinical and basic science data indicating that PRs are likely more than a bystander in AMD and play a significant role in AMD pathogenesis.},
}
@article {pmid39930167,
year = {2025},
author = {Jaskoll, S and Kramer, A and Elbaz-Hayoun, S and Rinsky, B and Grunin, M and Tiosano, L and Vofo, BN and Shwartz, Y and Chowers, I},
title = {Genotype-Phenotype Correlations and Genetic Risk Assessment in Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {21-25},
pmid = {39930167},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/genetics/pathology ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Phenotype ; *Genetic Association Studies ; Risk Assessment ; Risk Factors ; Genotype ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of irreversible vision loss in the elderly, presents researchers and clinicians with a complex challenge due to its multifaceted etiology and phenotype. The difficulty in developing effective treatments, especially for atrophic AMD, is an ongoing concern. Genetics plays a significant role in AMD's pathogenesis, with 52 variants in 34 loci linked to AMD based on a genome-wide association study. The association of genetic burden to the phenotypic and progression features of AMD is a current focus in the field. This perspective presents available information on phenotype-genotype correlations in AMD and on future directions in AMD genetic research which may be further corroborated with specific phenotypes and progression patterns to eventually develop personalized follow-up and therapeutic strategies.},
}
@article {pmid39930166,
year = {2025},
author = {Daniel, S and Ortega, AJ and Hulleman, JD},
title = {RPE Basal Lamina Biology and Pathophysiology Related to Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {15-19},
pmid = {39930166},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/pathology/physiopathology/metabolism ; *Retinal Pigment Epithelium/pathology/metabolism/physiopathology ; Animals ; *Basement Membrane/pathology/metabolism/physiopathology ; },
abstract = {Age-related macular degeneration (AMD) is a progressive eye disease that primarily affects the central part of the retina and is a leading cause of vision impairment worldwide (Wong WL, Su X, Li X, Lancet Glob Health 2:e106-116, 2014). Sub-retinal pigment epithelium (RPE) deposits represent a broadly defined term encompassing compositionally and anatomically distinct protein and lipid aggregates (i.e., drusen, basal linear deposits [BLinDs], and basal laminar deposits [BLamDs]). These deposits play a pivotal role in the pathogenesis of AMD and act as both key indicators and contributors to disease progression (van der Schaft TL, de Bruijn WC, Mooy CM, de Jong PT, Graefes Arch Clin Exp Ophthalmol 231:470-475, 1993; Sarks SH, Arnold JJ, Killingsworth MC, Sarks JP, Br J Ophthalmol 83:358-368, 1999; Sura AA, Chen L, Messinger JD, Invest Ophthalmol Vis Sci 61:19, 2020). Thus, understanding factors that influence sub-RPE deposit formation is crucial, especially in the context of retinal health and disease (Loeffler KU, Lee WR, Br J Ophthalmol 82:1104-1105, 1998; Sarks SH, Arnold JJ, Killingsworth MC, Sarks JP, Br J Ophthalmol 83:358-368, 1999). In this mini review, we have gathered and discussed valuable insights to provide a comprehensive overview focusing on BLamDs and their relevance to retinal disease.},
}
@article {pmid39930165,
year = {2025},
author = {Foster, E and Carr, AJ},
title = {Macrophages and Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {9-13},
pmid = {39930165},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/immunology/pathology ; *Macrophages/immunology/pathology ; Animals ; Retinal Pigment Epithelium/pathology/immunology ; Aging/immunology ; },
abstract = {Age-related macular degeneration (AMD) is characterised by the dysfunction of the retinal pigment epithelium (RPE), deposition of drusen and degeneration of the overlying photoreceptors, leading to the loss of central vision. AMD is a complex and multifactorial disease, with the greatest risk factor being age. As we age, changes occur to our immune system, a phenomenon known as inflammageing. There is mounting evidence indicating a role for the immune system in the development, progression, pathology and potentially, treatment of AMD. However, the specific contribution played by immune cells remains unclear. This chapter discusses evidence implicating a role for the circulating macrophages in AMD.},
}
@article {pmid39930164,
year = {2025},
author = {Stürzbecher, L and Strauss, O},
title = {Associations of the Adaptive Immune System and Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1468},
number = {},
pages = {3-7},
pmid = {39930164},
issn = {0065-2598},
mesh = {Animals ; *Adaptive Immunity ; Humans ; *Macular Degeneration/immunology/pathology ; *Retina/immunology/pathology ; Disease Models, Animal ; Mice ; T-Lymphocytes/immunology ; },
abstract = {In recent years, the adaptive immune system has gained a significant amount of attention due to its potential role in age-related macular degeneration (AMD). Orthologous approaches including cellular and animal models as well as pilot clinical trials have paved the way to understand the occurrence, alterations, and interactions of T cell populations in the retina. Interestingly, the notions of the involvement of the adaptive immune system in AMD have also gained support through recent findings in various neurodegenerative and chronic low-grade diseases, including multiple sclerosis, Parkinson's disease, or arteriosclerosis. In this group of pathologies, cells of the adaptive immune system bypass immune barriers and fuel inflammatory processes at immune-privileged sites. These findings have pointed at immunosenescence as a critical pro-inflammatory process involving T cell biology. Using a murine model relevant to the pathophysiology of geographic atrophy, we have demonstrated that specific populations of memory T cells are recruited to the retina prior to neurodegeneration. The investigation of these retinas at later degenerative stages revealed the presence of activated cytotoxic T cells at the injury site. These compelling results support the participation of the adaptive immune system in retina degeneration and highlight the potential of T cell populations as an early therapeutic target to slow the progression of AMD.},
}
@article {pmid39929889,
year = {2025},
author = {Lizama, BN and Keeling, E and Cho, E and Malagise, EM and Knezovich, N and Waybright, L and Watto, E and Look, G and Di Caro, V and Caggiano, AO and Ratnayaka, JA and Hamby, ME},
title = {Sigma-2 receptor modulator CT1812 alters key pathways and rescues retinal pigment epithelium (RPE) functional deficits associated with dry age-related macular degeneration (AMD).},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {4256},
pmid = {39929889},
issn = {2045-2322},
support = {R01 AG058660/AG/NIA NIH HHS/United States ; R42 AG052249/AG/NIA NIH HHS/United States ; 1RO1AG058660-01/NH/NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Animals ; *Receptors, sigma/metabolism ; Humans ; Mice ; Mice, Transgenic ; *Geographic Atrophy/metabolism/drug therapy/pathology ; *Macular Degeneration/metabolism/drug therapy/pathology ; Amyloid beta-Peptides/metabolism ; Disease Models, Animal ; Oxidative Stress/drug effects ; Signal Transduction/drug effects ; Alzheimer Disease/metabolism ; },
abstract = {Trafficking defects in retinal pigmented epithelial (RPE) cells contribute to RPE atrophy, a hallmark of geographic atrophy (GA) in dry age-related macular degeneration (AMD). Dry AMD pathogenesis is multifactorial, including amyloid-β (Aβ) accumulation and oxidative stress-common features of Alzheimer's disease (AD). The Sigma-2 receptor (S2R) regulates lipid and protein trafficking, and S2R modulators reverse trafficking deficits in neurodegeneration in vitro models. Given overlapping mechanisms contributing to AD and AMD, S2R modulator effects on RPE function were investigated. The S2R modulator CT1812 is in clinical trials for AD, dementia with Lewy bodies, and GA. Leveraging AD trials testing CT1812, unbiased analyses of patient biofluid proteomes revealed that proteins altered by CT1812 associated with GA and macular degeneration disease ontologies and overlapped with proteins altered in dry AMD. Differential expression analysis of RPE transcripts from APP-Swedish/London mutant transgenic mice, a model featuring Aβ accumulation, revealed reversal of autophagy/trafficking transcripts in S2R modulator-treated animals versus vehicle toward healthy control levels. Photoreceptor outer segment (POS) trafficking in human RPE cells showed deficits in response to Aβ1-42 or hydrogen peroxide compared to vehicle. S2R modulators normalized stressor-induced POS trafficking deficits, resembling healthy control. Taken together, S2R modulation may provide a novel therapeutic strategy for dry AMD.},
}
@article {pmid39929700,
year = {2025},
author = {Zeng, X and Chen, R and Zhang, X and Su, T and Wang, Y and Hu, Y and Shang, X and Shi, D and Yu, H},
title = {Associations between a healthy lifestyle score and retinal neurovascular health.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {8},
pages = {858-867},
doi = {10.1136/bjo-2024-326184},
pmid = {39929700},
issn = {1468-2079},
mesh = {Humans ; Male ; Female ; Aged ; *Healthy Lifestyle/physiology ; Tomography, Optical Coherence/methods ; Middle Aged ; *Retinal Vessels/diagnostic imaging ; Risk Factors ; United Kingdom/epidemiology ; Exercise/physiology ; *Macular Degeneration/epidemiology ; *Retinal Vein Occlusion/epidemiology/physiopathology ; },
abstract = {AIMS: To investigate the associations between a healthy lifestyle score and retinal neurovascular health, and explore whether lower inflammation levels mediate these associations.<br><br>METHODS: This study is based on the UK Biobank. The healthy lifestyle score ranged from 0 to 6 and comprised physical activity, diet, sleep duration, smoking status, alcohol consumption and bodyweight. Outcomes included retinal diseases (age-related macular degeneration (AMD) and retinal vascular occlusion (RVO)) from hospital admission records (378&#x2009;648 participants), retinal vascular metrics from retinal photography (32&#x2009;226 participants) and retinal neural metrics from optical coherence tomography (42&#x2009;557 participants). An INFLA-score was used to characterise inflammation levels.<br><br>RESULTS: Participants with better healthy life score (scored from 5 to 6) were associated with a 29% lower risk of AMD, 25% lower risk of RVO, 2% increase in artery-to-vein ratio (AVR), 0.22&#x2009;&#xb5;m increase in central retinal artery equivalent, 0.36&#x2009;&#xb5;m decrease in central retinal vein equivalent (CRVE), 0.004 increase in fractal dimension, 0.38&#x2009;&#xb5;m increase in retinal nerve fibre layer, 0.69&#x2009;&#xb5;m increase in ganglion cell-inner plexiform layer (GCIPL) and 0.35&#x2009;&#xb5;m increase in photoreceptor segment (PS) compared with those with worst lifestyle score (scored from 0 to 1) (all ptrend<0.01). In addition, INFLA-score partially mediated the associations between healthy lifestyle score and increased risk of AMD (mediated proportion (MP): 14.8%), higher AVR (MP: 12.76%), narrower CRVE (MP: 24.49%), thicker GCIPL (MP: 4.97%) and thicker PS (MP: 26.86%).<br><br>CONCLUSION: Great adherence to a healthier lifestyle was associated with better retinal health in a dose-response manner. Lower inflammation partially mediated the association between a healthy lifestyle score and retinal health.},
}
@article {pmid39929178,
year = {2025},
author = {Shiromani, S and Leef, D and Jain, N and Yan, J},
title = {Ciliary Neurotrophic Factor Implant in Geographic Atrophy from Age-related Macular Degeneration: A Long-Term Case Study.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001725},
pmid = {39929178},
issn = {1937-1578},
abstract = {PURPOSE: To report a case of thirteen-year long progression of geographic atrophy (GA) from dry age-related macular degeneration (AMD) with ciliary neurotrophic factor (CNTF) implant, NT-501, in one eye, compared to the untreated contralateral eye.<br><br>METHODS: Using sequential images from 2012 to 2024, the macular GA and peripapillary atrophy was identified as areas of definitely decreased autofluorescence on fundus autofluorescence (FAF) and clearly delineated areas of hyperreflectivity on near infrared reflectance (NIR-R). Optical coherence tomography B scans confirmed areas of complete retinal pigment epithelium and outer retinal atrophy to support FAF grading.<br><br>RESULTS: A 76-year-old male received the CNTF implant in the right eye in August 2011. Macular GA area on short wavelength FAF exhibited growth from 4.51 mm2 (8/2012) to 14.46 mm2 (6/2020), in the treated right eye, and from 3.2 mm2 to 14.92 mm2 in the untreated left eye. The linearized growth rates were 0.21 mm/y (right) and 0.26 mm/y (left), showing a 16.3% difference. A similar pattern was seen on green laser FAF from 2018 to 2024, with peripapillary atrophy progression rates of 0.2 mm2/y (right) and 1.03 mm2/y (left).<br><br>CONCLUSIONS: Notably, the implanted eye, exhibited less progression of macular GA and peripapillary atrophy. While acknowledging the limitations of a single case, we highlight the potential benefits of using the CNTF implant, a one-time surgical procedure, in reducing the treatment burden for atrophic AMD patients. We hope to see further reports from other sites that participated in this compassionate use protocol for NT-501 in atrophic AMD.},
}
@article {pmid39928312,
year = {2025},
author = {Wang, X and Hoshi, S and Liu, R and Corradetti, G and Ip, M and Sarraf, D and Sadda, SR and Zhang, Y},
title = {Photoreceptor Function and Structure in Retinal Areas With Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {2},
pages = {27},
pmid = {39928312},
issn = {1552-5783},
support = {R01 EY024378/EY/NEI NIH HHS/United States ; R01 EY034218/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Aged ; Female ; Male ; Ophthalmoscopy/methods ; *Macular Degeneration/physiopathology/diagnosis ; Aged, 80 and over ; Visual Acuity/physiology ; *Photoreceptor Cells, Vertebrate/physiology/pathology ; Retinal Drusen/physiopathology ; *Retina/physiopathology/pathology ; Middle Aged ; },
abstract = {PURPOSE: To assess retinal light sensitivity in regions with intraretinal hyperreflective foci (IHRFs) in eyes with intermediate age-related macular degeneration (AMD) and examine the photoreceptor structure in these areas using adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography (OCT).<br><br>METHODS: A retrospective analysis was conducted on 82 eyes of 57 subjects (age: 76.4 &#xb1; 7.0 years) with intermediate AMD. IHRFs were identified in OCT B-scans. Drusen and subretinal drusenoid deposits (SDDs) were evaluated using multimodal imaging. Photoreceptor structure was assessed with AOSLO, and choroidal and retinal thicknesses were measured in areas with IHRFs. In 16 eyes, mesopic and scotopic light sensitivities were compared in regions with and without IHRFs but with similar SDD/drusen load in the same eye.<br><br>RESULTS: Retinal areas with IHRFs had significantly reduced mesopic (17.19 &#xb1; 5.68 dB vs. 18.49 &#xb1; 5.35 dB, P = 0.0029) and scotopic (8.39 &#xb1; 5.67 dB vs. 9.72 &#xb1; 6.28 dB, P = 0.0096) light sensitivity compared to areas without IHRFs. AOSLO revealed disrupted cone photoreceptor structure in IHRF regions. Choroidal thickness beneath areas with IHRFs was thinner than in those without IHRFs (196.71 &#xb1; 73.31 &#xb5;m vs. 202.37 &#xb1; 70.64 &#xb5;m, P = 0.0211). Retinal thickness in regions with IHRFs was not significantly different from those without IHRFs (320.40 &#xb1; 31.16 &#xb5;m vs. 316.92 &#xb1; 26.32 &#xb5;m, P = 0.3537).<br><br>CONCLUSIONS: IHRF presence is associated with localized reduced visual function and photoreceptor degeneration in intermediate AMD. Prospective studies are warranted to further investigate the mechanisms of photoreceptor and sensitivity loss in the context of IHRF.},
}
@article {pmid39927516,
year = {2025},
author = {Malkin, A and Deemer, A and Contreras, M and Edmonds, H and Quan, AC and Koskey, J and Walters, MK and Ng, SM and Lawrenson, JG},
title = {Self-management interventions for quality of life in adults with visual impairment.},
journal = {The Cochrane database of systematic reviews},
volume = {2},
number = {2},
pages = {CD015790},
pmid = {39927516},
issn = {1469-493X},
mesh = {Humans ; *Quality of Life ; Randomized Controlled Trials as Topic ; *Self-Management/methods ; *Vision Disorders/therapy/psychology ; Aged ; Activities of Daily Living ; Adult ; Middle Aged ; Bias ; },
abstract = {RATIONALE: Visual impairment is a major health concern that predominantly impacts older adults due to age-related ocular diseases. Visual impairment affects more than 2200 million people worldwide and may lead to functional and psychological decline, emphasizing the need for effective self-management interventions. Self-management interventions aim to enhance individuals' abilities to manage their condition, maintain activities of daily living, and improve overall well-being.<br><br>OBJECTIVES: To assess the effects of self-management interventions on quality of life in adults with visual impairment compared with inactive or active (usual care) control interventions.<br><br>SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and two trial registries, together with reference checking and contact with study authors to identify studies that are included in the review. The latest search date was on 19 May 2024.<br><br>ELIGIBILITY CRITERIA: We included parallel-group randomized controlled trials (RCTs) comparing multifaceted self-management interventions in adults with acquired visual impairment (including dual sensory impairment).<br><br>OUTCOMES: Outcomes assessed were overall and subscores of health-related quality of life (HRQoL) and vision-related quality of life (VRQoL) scores at the end of follow-up, adverse events during the study period, and vision-related living performance measures at the end of follow-up.<br><br>RISK OF BIAS: We assessed the risk of bias for three outcomes reported in a summary of findings table using the Cochrane RoB 2 tool.<br><br>SYNTHESIS METHODS: We synthesized results for each outcome using meta-analysis where possible, by calculating standardized mean difference (SMD) or mean difference (MD) with 95% confidence interval (CI) for continuous outcomes and risk ratio (RR) with 95% CIs for dichotomous outcomes. Where this was not possible due to the nature of the data, we provided a narrative summary of the results. We used GRADE to assess certainty of evidence for prespecified outcomes.<br><br>INCLUDED STUDIES: We included 20 parallel-group RCTs that enrolled 3151 participants. The size of studies ranged from 30 to 323 participants with a median of 153 participants. Studies were conducted in Asia (two studies), Australia (two), Europe (six), and North America (10) in academic medical centers, hospitals, low-vision clinics, private practice, rehabilitation centers, and Veterans Affairs medical facilities. The participants were older adults with a mean age across the included studies ranging from 60 to 84 years. The mean logarithm of the minimum angle of resolution (logMAR) visual acuity ranged from 0.15 to 1.11. Age-related macular degeneration was the predominant cause of low vision in 15 studies. We did not identify any eligible studies for adults with dual sensory impairment. One study was funded by industry, whereas others received a research grant or support from a non-profit organization or foundation. Multifaceted self-management interventions included in this review were diverse. The control group was placed on a wait list, while other active controls included usual care, optical aids, or low-vision rehabilitation.<br><br>SYNTHESIS OF RESULTS: We rated the overall risk of bias of included studies as low or some concerns. The meta-analysis revealed consistent findings across different outcomes and comparisons. For HRQoL, evidence suggests that self-management intervention may result in little to no difference in HRQoL (change score: SMD -0.09, 95% CI -0.33 to 0.15; I[2] = 46%; 3 studies, 568 participants; final value: SMD -0.15, 95% CI -0.38 to 0.08; I[2] = 31%; 3 studies, 459 participants; low-certainty evidence). This finding remained consistent regardless of whether wait list or active control was the comparator. For VRQoL, multifaceted self-management interventions may result in little to no difference in VRQoL change score compared to active control (SMD -0.12, 95% CI -0.33 to 0.10; I[2] = 48%; 4 studies, 733 participants; low-certainty evidence). The evidence from six studies by final values suggests that self-management intervention may not improve VRQoL compared to control treatment in the longer-term (6 to 24 months) (SMD -0.01, 95% CI -0.14 to 0.13; I[2] = 0%; 6 studies, 864 participants; low-certainty evidence). The conclusion was unchanged, irrespective of the comparator used. We judged the certainty of evidence for both HRQoL and VRQoL as low according to GRADE criteria, downgrading one level for imprecision and one level for unexplained heterogeneity. For harms, self-management interventions may not affect the risk of adverse events (RR 1.14, 95% CI 0.78 to 1.66; I&#xb2; = 0%; 2 studies, 255 participants; low-certainty evidence). Of four studies that reported adverse events, three studies observed no treatment-related adverse events. One study referred 12 (34%) participants to the general medical practitioner for depressive symptoms in the intervention group compared with seven (22%) participants in the wait list comparison group.<br><br>AUTHORS' CONCLUSIONS: In this review, we found low-certainty evidence that multifaceted self-management interventions have little or no effects on improving HRQoL and VRQoL for adults with visual impairment. Research is needed to develop more sensitive measures of quality of life and to assess the benefit of such interventions across a broader demographic, including different stages of vision impairment and people with dual-sensory impairment.<br><br>FUNDING: Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health.<br><br>REGISTRATION: Protocol available via doi.org/10.1002/14651858.CD015790.},
}
@article {pmid39927462,
year = {2025},
author = {Biswas, P and Woodard, DR and Hollingsworth, TJ and Khan, NW and Lazaro, DR and Berry, AM and Dagar, M and Pan, Y and Garland, D and Shaw, PX and Oka, C and Iwata, T and Jablonski, MM and Ayyagari, R},
title = {Ablation of Htra1 leads to sub-RPE deposits and photoreceptor abnormalities.},
journal = {JCI insight},
volume = {10},
number = {3},
pages = {},
pmid = {39927462},
issn = {2379-3708},
support = {R01 EY021237/EY/NEI NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; U24 EY033699/EY/NEI NIH HHS/United States ; R01 EY030591/EY/NEI NIH HHS/United States ; R01 EY031663/EY/NEI NIH HHS/United States ; P30 EY022589/EY/NEI NIH HHS/United States ; T32 EY026590/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism ; Mice ; *Retinal Pigment Epithelium/pathology/metabolism/ultrastructure ; Mice, Knockout ; *Macular Degeneration/pathology/genetics/metabolism ; Disease Models, Animal ; Bruch Membrane/pathology/metabolism ; Retina/pathology/metabolism ; Mice, Inbred C57BL ; },
abstract = {The high-temperature requirement A1 (HTRA1), a serine protease, has been demonstrated to play a pivotal role in the extracellular matrix (ECM) and has been reported to be associated with the pathogenesis of age-related macular degeneration (AMD). To delineate its role in the retina, the phenotype of homozygous Htra1-KO (Htra1-/-) mice was characterized to examine the effect of Htra1 loss on the retina and retinal pigment epithelium (RPE) with age. The ablation of Htra1 led to a significant reduction in rod and cone photoreceptor function, primary cone abnormalities followed by rods, and atrophy in the RPE compared with WT mice. Ultrastructural analysis of Htra1-/- mice revealed RPE and Bruch's membrane (BM) abnormalities, including the presence of sub-RPE deposits at 5 months (m) that progressed with age accompanied by increased severity of pathology. Htra1-/- mice also displayed alterations in key markers for inflammation, autophagy, and lipid metabolism in the retina. These results highlight the crucial role of HTRA1 in the retina and RPE. Furthermore, this study allows for the Htra1-/- mouse model to be utilized for deciphering mechanisms that lead to sub-RPE deposit phenotypes including AMD.},
}
@article {pmid39927457,
year = {2025},
author = {Pan, WW and Wubben, TJ and Zacks, DN},
title = {Promising therapeutic targets for neuroprotection in retinal disease.},
journal = {Current opinion in ophthalmology},
volume = {36},
number = {3},
pages = {247-252},
doi = {10.1097/ICU.0000000000001123},
pmid = {39927457},
issn = {1531-7021},
mesh = {Humans ; *Neuroprotective Agents/therapeutic use ; *Retinal Diseases/therapy ; *Neuroprotection/physiology ; *Genetic Therapy/methods ; Animals ; },
abstract = {PURPOSE OF REVIEW: Neurodegeneration is a common endpoint of various blinding retinal diseases. Yet, despite exciting advances in disease treatment, there continues to exist a critical need for the development of neuroprotective strategies to prevent retinal cell death. Here, we summarize the recent advances in neuroprotective strategies.<br><br>RECENT FINDINGS: From laboratory deciphering of the mechanisms involved in disease, many novel neuroprotective strategies have emerged and are currently under investigation for the treatment of various retinal and ocular diseases such as inherited retinal degeneration, retinal detachment, diabetic retinopathy, age-related macular degeneration, macular telangiectasia type 2, and glaucoma. These strategies include gene therapies, Fas inhibition, and targeting inflammatory, metabolic and reduction-oxidation abnormalities. Interestingly, investigation of several treatments across different diseases suggests shared neuroprotection mechanisms that can be targeted regardless of the particular disease.<br><br>SUMMARY: Retinal neuroprotection can improve treatment of different retinal diseases. Fortunately, the current landscape, with a plethora of novel neuroprotective therapies, portends a better future for patients.},
}
@article {pmid39925414,
year = {2025},
author = {Heiden, R and Hannig, L and Bernhard, JS and Vallon, M and Schlecht, A and Hofmann, N and Ergün, S and Hoschek, F and Wagner, M and Neueder, A and Förster, CY and Braunger, BM},
title = {Tissue origin of endothelial cells determines immune system modulation and regulation of HIF-1α-, TGF-β-, and VEGF signaling.},
journal = {iScience},
volume = {28},
number = {2},
pages = {111740},
pmid = {39925414},
issn = {2589-0042},
abstract = {Tight junctions of vascular endothelial cells in the central nervous system form the blood-brain and inner blood-retinal barriers, the integrity of which are further influenced by neighboring cells such as pericytes, astrocytes/Müller glial processes, and immune cells. In addition, the retina is shielded from the fenestrated endothelium of the choriocapillaris by the epithelial barrier of the retinal pigment epithelium. Dysfunction of the blood retinal barriers and/or proliferation of retinal and choroidal endothelial cells are caused by late stages of diabetic retinopathy (DR) and neovascular age-related macular degeneration (nAMD), the main causes of blindness in western countries. To elucidate endothelial-derived pathomechanisms in DR and nAMD, we established immortalized mouse cell lines of retinal and choroidal endothelial cells and immortalized brain endothelial cells as CNS-derived controls. We then used immunofluorescence staining, state-of-the-art long-range RNA sequencing and monolayer permeability assays to compare the functional state of these cells depending on their tissue origin. We furthermore demonstrate that activation of the wingless-type MMTV integration site (Wnt)/β-catenin signaling pathway restored blood brain/retinal barrier properties in brain and retinal endothelial cells, but unexpectedly increased permeability of choroidal endothelial cells. Transcriptome profiling showed that depending on the tissue origin of endothelial cells, regulation of the immune system was altered and pathways such as hypoxia-inducible factor (HIF)-1/2α, transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF) were differentially regulated, strongly indicating their contribution in the molecular pathogenesis of DR and nAMD. These findings significantly increase the understanding of the vascular biology of endothelial cells, highlighting the fact that depending on their tissue origin, their contribution to vascular pathologies varies.},
}
@article {pmid39923899,
year = {2025},
author = {Bala, S and Barbosa, GCS and Mohan, N and Srivastava, SK and Kaiser, PK and Sastry, A and Babiuch, AS and Sears, J and Talcott, KE and Yuan, A and Rachitskaya, A and Ehlers, JP and Schachat, AP and Lin, P and Sharma, S and Mammo, DA},
title = {Initial Functional and Anatomical Outcomes of High-dose Aflibercept 8 mg in Exudative Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {8},
pages = {756-766},
doi = {10.1016/j.oret.2025.02.002},
pmid = {39923899},
issn = {2468-6530},
mesh = {Humans ; Retrospective Studies ; Male ; *Visual Acuity ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Aged ; Follow-Up Studies ; Treatment Outcome ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; *Macula Lutea/pathology ; Aged, 80 and over ; Dose-Response Relationship, Drug ; Fundus Oculi ; Middle Aged ; },
abstract = {PURPOSE: To evaluate the short-term outcomes of patients with exudative neovascular age-related macular degeneration (nAMD) treated with high-dose aflibercept (HDA) 8.0 mg, focusing on anatomical and functional changes, as well as the feasibility of extending treatment intervals in a clinical practice setting.<br><br>DESIGN: Retrospective, noncomparative cohort study.<br><br>SUBJECTS: Two hundred nineteen eyes from 184 patients with nAMD who received &#x2265;3 HDAs between August 2023 and October 2024.<br><br>METHODS: Patients included in this study were either treatment-na&#xef;ve or had been previously treated with other anti-VEGF agents. Clinical outcomes, including best-corrected visual acuity (BCVA) and macular OCT parameters, were evaluated at baseline and after each HDA.<br><br>MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes able to sustain an 8 &#xb1; 1-week or longer treatment interval without anatomical deterioration. The secondary outcomes included anatomical and functional changes.<br><br>RESULTS: The average follow-up time was 22.9 &#xb1; 4.9 weeks; 209 eyes (95.4%) were previously treated, and 10 eyes (4.6%) were treatment-na&#xef;ve. After the first 3 injections, 206 eyes (94.1%) received a fourth HDA, and 70 eyes (31.9%) received a fifth HDA. One hundred two eyes (46.6%) of the total cohort with an interval shorter than 8 weeks after 3 initial injections had persistent macular fluid; 24 eyes (11.0%) were switched to another anti-VEGF agent. Overall, the mean BCVA was 61.9 &#xb1; 21.7 ETDRS letters at baseline and 61.7 &#xb1; 22.6 at the final visit, with no statistically significant difference observed (P = 0.934). Central subfield thickness and pigment epithelial detachment height remained stable. Significant reductions were observed in subretinal (54.3%-41.1%, P = 0.006) and intraretinal fluid (53.9%-39.3%, P = 0.002). Among previously treated eyes, the mean preswitch treatment interval was 5.8 &#xb1; 2.5 weeks and increased to 7.4 &#xb1; 2.2 weeks after the 3 initial injections (P < 0.0001).<br><br>CONCLUSIONS: High-dose aflibercept demonstrated stable BCVA and significant reductions in macular fluid during the follow-up period. A considerable proportion of patients were unable to extend treatment intervals to &#x2265;8 weeks due to persistent macular fluid. These findings suggest that HDA maintains functional stability while improving anatomic outcomes, though challenges in managing chronic nAMD in a clinical-practice setting may limit the ability to extend treatment intervals.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39922885,
year = {2025},
author = {Yang, H and Huang, H and Pu, K},
title = {A cross-tissue transcriptome-wide association study identified susceptibility genes for age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {4788},
pmid = {39922885},
issn = {2045-2322},
mesh = {Humans ; *Macular Degeneration/genetics ; *Genetic Predisposition to Disease ; *Genome-Wide Association Study ; *Transcriptome/genetics ; Quantitative Trait Loci ; Polymorphism, Single Nucleotide ; Mendelian Randomization Analysis ; Gene Expression Profiling ; },
abstract = {Age-related macular degeneration (AMD) is a complex multifactorial disease with a significant genetic component. Despite extensive research efforts, the underlying molecular mechanisms remain elusive, necessitating innovative approaches to identify specific genes involved in the pathogenesis of AMD and to elucidate their functional mechanisms. A transcriptome-wide association study (TWAS) was conducted by integrating eQTL data from 49 tissues of the Genotype-Tissue Expression Project (GTEx) v8 and AMD data from FinnGen R10. The Unified Test for Molecular Signatures (UTMOST) and Functional Summary-based Imputation (FUSION) were used to evaluate gene associations with AMD across tissues and within individual tissues, respectively. Multi-marker Analysis of Genomic Annotation (MAGMA) was employed to validate results and identify reliable susceptibility genes, followed by summary data-based Mendelian randomization (SMR) and colocalization analyses to explore causal associations. The cross-tissue and single-tissue TWAS analyses identified 12 reliable AMD-associated genes. MAGMA analysis confirmed 6 of these as reliable susceptibility genes. SMR analysis provided further validation of these genes, although colocalization results were not significant. This study identified six susceptibility genes associated with the risk of AMD through a cross-tissue TWAS, providing new insights into the potential systemic regulatory mechanisms underlying AMD.},
}
@article {pmid39922526,
year = {2025},
author = {Feldman, TB and Yakovleva, MA and Ostrovsky, MA},
title = {Retinoids in lipofuscin granules from retinal pigment epithelium as biomarkers of the damaging effect of ionizing radiation.},
journal = {Experimental eye research},
volume = {252},
number = {},
pages = {110270},
doi = {10.1016/j.exer.2025.110270},
pmid = {39922526},
issn = {1096-0007},
mesh = {Humans ; *Lipofuscin/metabolism/radiation effects ; *Retinal Pigment Epithelium/radiation effects/metabolism ; *Retinoids/metabolism ; Biomarkers/metabolism ; *Radiation Injuries/metabolism/diagnosis ; Aged ; *Radiation, Ionizing ; Male ; Oxidation-Reduction ; Middle Aged ; Female ; },
abstract = {Lipofuscin granules accumulate in the retinal pigment epithelium with age, especially in patients with visual diseases, including progressive age-related macular degeneration. Retinoids (bisretinoids and their oxidation products) are major sources of lipofuscin granule fluorescence. The aim of this work was to analyze the radiation-mediated oxidation of retinoids in lipofuscin granules obtained from the human cadaver eye retinal pigment epithelium. Fluorescent and chromatographic analyses of retinoids were performed before and after irradiation of lipofuscin granules with accelerated protons. The fluorescent properties of chloroform extracts from irradiated lipofuscin granules exhibited an increase in fluorescence intensity in the short-wavelength region of 555 nm. This change is associated with an increase in the quantity of retinoid oxidation cytotoxic products after accelerated proton exposure. The radiation-induced oxidation of retinoids caused a noticeable change in its fluorescent properties allows us to consider this phenomenon as a potential opportunity for non-invasively assessment of the degree of radiation exposure and its relative biological effect in humans. Thus, this research proposes a new strategy for assessing the extent of radiation exposure to humans, which evaluates the effects of ionizing radiation on human eye tissues. This approach is based on the principles of the modern non-invasive method of fundus autofluorescence used in ophthalmology for the diagnosis of the retina and retinal pigment epithelium degenerative diseases.},
}
@article {pmid39921001,
year = {2025},
author = {Shen, LL and Kaiser, PK and Liu, J and Stewart, JM and Heyang, M and Keenan, TDL and Sunness, JS and Rosenfeld, PJ and Chew, EY and Del Priore, LV},
title = {Determinants of Four-Year Visual Acuity Loss in Geographic Atrophy: An Analysis of Age-Related Eye Disease Study and Age-Related Eye Disease Study 2.},
journal = {Ophthalmology},
volume = {132},
number = {7},
pages = {785-798},
doi = {10.1016/j.ophtha.2025.01.028},
pmid = {39921001},
issn = {1549-4713},
mesh = {Humans ; *Visual Acuity/physiology ; *Geographic Atrophy/physiopathology/diagnosis/drug therapy ; Male ; Female ; Aged ; Disease Progression ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; Middle Aged ; Fluorescein Angiography ; Fovea Centralis/pathology ; Angiogenesis Inhibitors/therapeutic use ; Macular Degeneration/physiopathology/complications/diagnosis ; },
abstract = {PURPOSE: To investigate the relationship between geographic atrophy (GA) progression and change in best-corrected visual acuity (BCVA) over 4 years and identify factors associated with faster BCVA loss.<br><br>DESIGN: Secondary analysis of 2 randomized controlled clinical trials.<br><br>PARTICIPANTS: Age-Related Eye Disease Study (AREDS) and AREDS2 participants with GA secondary to nonexudative age-related macular degeneration.<br><br>METHODS: Baseline and annual color fundus photographs were assessed for GA area and proximity to the foveal center. Best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study logarithm of the minimum angle of resolution (logMAR) charts. Analyses included BCVA change over 4 years, with the relationship of BCVA decline with GA progression and other baseline factors examined using multivariable linear mixed-effects models.<br><br>MAIN OUTCOME MEASURES: The primary outcome was BCVA change over 4 years. Secondary outcomes included BCVA change from baseline to years 1, 2, and 3.<br><br>RESULTS: We included 1351 eyes from 994 participants, including 594 eyes from 464 participants with 4-year BCVA follow-up. Higher baseline BCVA, smaller baseline GA proximity to the foveal center, and greater GA growth rate were each independently associated with larger BCVA loss over 4 years (each P < 0.001). Among the 594 eyes with 4-year BCVA data, 69 eyes with a baseline BCVA < 40 letters (Snellen equivalent of 20/160 or worse) and 42 eyes with baseline GA located more than 1 mm from the foveal center did not experience significant BCVA loss over 4 years. In contrast, 483 eyes that met both criteria of baseline BCVA &#x2265; 40 letters and GA lesions involving or within 1 mm of the foveal center showed significant BCVA loss over 4 years (mean change = -11.33 letters [95% confidence interval = -12.80 to -9.84]), with faster GA progression associated with larger BCVA loss (P < 0.001).<br><br>CONCLUSIONS: In this cohort, eyes with GA involving or within 1 mm of the foveal center and a baseline BCVA of &#x2265; 40 letters appeared more likely to experience significant BCVA loss, suggesting these eyes may benefit more from therapies that slow GA progression. Our findings support a personalized approach to managing patients with GA, potentially guiding the design of future GA trials.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39920843,
year = {2025},
author = {Mantel, I and Lasagni Vitar, RM and De Zanet, S},
title = {Modeling pegcetacoplan treatment effect for atrophic age-related macular degeneration with AI-based progression prediction.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {14},
pmid = {39920843},
issn = {2056-9920},
abstract = {BACKGROUND: To illustrate the treatment effect of Pegcetacoplan for atrophy secondary to age-related macular degeneration (AMD), on an individualized topographic progression prediction basis, using a deep learning model.<br><br>METHODS: Patients (N&#x2009;=&#x2009;99) with atrophy secondary to AMD with longitudinal optical coherence tomography (OCT) data were retrospectively analyzed. We used a previously published deep-learning-based atrophy progression prediction algorithm to predict the 2-year atrophy progression, including the topographic likelihood of future retinal pigment epithelial and outer retinal atrophy (RORA), according to the baseline OCT input. The algorithm output was a step-less individualized topographic modeling of the RORA growth, allowing for illustrating the progression line corresponding to an 80% growth compared to the natural course of 100% growth.<br><br>RESULTS: The treatment effect of Pegcetacoplan was illustrated as the line when 80% of the growth is reached in this continuous model. Besides the well-known variability of atrophy growth rate, our results showed unequal growth according to the fundus location. It became evident that this difference is of potential functional interest for patient outcomes.<br><br>CONCLUSIONS: This model based on an 80% growth of RORA after two years illustrates the variable effect of treatment with Pegcetacoplan according to the individual situation, supporting personalized medical care.},
}
@article {pmid39920326,
year = {2025},
author = {Huber, AL and Bauer, A and Beirer, J and Frede, K and Kirchmair, K and Angermann, R and Rehak, M and Zehetner, C and Nowosielski, Y},
title = {Systemic counterregulatory response of angiopoietin-2 after intravitreal injections with faricimab for nAMD.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {5},
pages = {1259-1267},
pmid = {39920326},
issn = {1435-702X},
mesh = {Humans ; *Angiopoietin-2/blood/antagonists &amp; inhibitors ; Intravitreal Injections ; Female ; Male ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Enzyme-Linked Immunosorbent Assay ; *Wet Macular Degeneration/drug therapy/diagnosis/blood/metabolism ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Follow-Up Studies ; Aged, 80 and over ; Treatment Outcome ; Fluorescein Angiography ; Recombinant Fusion Proteins/administration &amp; dosage ; Visual Acuity ; Macula Lutea/pathology ; Antibodies, Bispecific ; },
abstract = {PURPOSE: Recently, a systemic counterregulatory response of angiopoietin-2 after intravitreal application of the anti vascular endothelial growth factor (anti-VEGF) drug aflibercept in neovascular age-related macular degeneration (nAMD) has been described. The aim of the study was to find out wether faricimab, a combined anti-VEGF/angiopoietin-2 drug, had an effect on systemic cytokine levels.<br><br>METHODS: 20 women and 11 men (mean age 79.5&#x2009;&#xb1;&#x2009;7.3 years) were included into this cohort study. Plama levels of VEGF-A and angiopoietin-2 were determined before and after intravitreal application of faricimab (6&#xa0;mg/0.05&#xa0;ml/eye) using ELISA-technique. These results were correlated with central macular thickness (CMT). Responders were defined as having had CMT thinning&#x2009;&#x2265;&#x2009;50&#xa0;&#x3bc;m.<br><br>RESULTS: CMT decreased from 384.8&#x2009;&#xb1;&#x2009;108.8&#xa0;&#x3bc;m prior to intravitreal injection (IVI) to 286.1&#x2009;&#xb1;&#x2009;63&#xa0;&#x3bc;m one month after IVI (p&#x2009;<&#x2009;0.0001). Angiopoietin-2 levels increased from 526.9&#x2009;&#xb1;&#x2009;129 pg/ml to 597.2&#x2009;&#xb1;&#x2009;174.8 pg/ml (p&#x2009;=&#x2009;0.0087) one week after IVI and dropped to 547.4&#x2009;&#xb1;&#x2009;165 pg/ml (ns) four weeks after IVI. Responders revealed higher angiopoietin-2 (p&#x2009;=&#x2009;0.0035) as well as higher VEGF-A (p&#x2009;=&#x2009;0.0248) levels throughout the study period compared to non-responders. Initial CMT revealed to be the only independent factor influencing CMT 4 weeks after IVI in linear regression models with a positive correlation between initial thickness and effect size.<br><br>CONCLUSION: The trending increase in systemic angiopoietin-2 levels, may be interpreted as an escape mechanism of the concomitant anti-VEGF component of therapy. Angiopoietin-2 levels could serve as a positive predictive factor of therapy response in the future. Further research regarding this effect as well as differences between responders and non-responders is mandatory.<br><br>KEY MESSAGES: What is known Bispecific antibodies may be more beneficial compared to monospecific antibodies in neovascular age related macular degeneration (nAMD). For monospecific antibodies, there are systemic effects on systemic vascular endothelial growth factor (VEGF) levels. What is new The knew bispecific antibody faricimab entails an increase in systemic angiopoietin-2 levels, as well as a decrease in VEGF levels. The increase in systemic angiopoietin-2 may be interpreted as a counterregulatory effect. The decrease in systemic VEGF levels resembles the effects of monospecific antibodies.},
}
@article {pmid39919162,
year = {2025},
author = {Lane, TR and Puhl, AC and Vignaux, PA and Pennypacker, KR and Ekins, S},
title = {Repurposing lapatinib as a triple antagonist of chemokine receptors 3, 4, and 5.},
journal = {Molecular pharmacology},
volume = {107},
number = {1},
pages = {100010},
doi = {10.1016/j.molpha.2024.100010},
pmid = {39919162},
issn = {1521-0111},
support = {R44 ES031038/ES/NIEHS NIH HHS/United States ; R44 GM122196/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Drug Repositioning/methods ; *Receptors, CCR3/antagonists &amp; inhibitors/metabolism ; *Lapatinib/pharmacology ; *Receptors, CCR4/antagonists &amp; inhibitors/metabolism ; Machine Learning ; Receptors, CCR5/metabolism ; CCR5 Receptor Antagonists/pharmacology ; },
abstract = {Chemokine receptors CCR3, CCR4, and CCR5 are G protein-coupled receptors implicated in diseases like cancer, Alzheimer's, asthma, human immunodeficiency virus (HIV), and macular degeneration. Recently, CCR3 and CCR4 have emerged as potential stroke targets. Although only the CCR5 antagonist maraviroc is US Food and Drug Administration-approved (for HIV), we curated data on CCR3, CCR4, and CCR5 antagonists from ChEMBL to develop and validate machine learning models. The top 5-fold cross-validation statistics for these models were high for both classification and regression models for CCR3 (receiver operating characteristic [ROC], 0.94; R[2] = 0.8), CCR4 (ROC, 0.98; R[2] = 0.57), and CCR5 (ROC, 0.96; R[2] = 0.78). The models for CCR3/4 were used to screen a small library of US Food and Drug Administration-approved drugs and 17 were initially tested in vitro against both CCR3/4 receptors. A promising compound lapatinib, a dual tyrosine kinase inhibitor, was identified as an antagonist for CCR3 (IC50, 0.7 μM) and CCR4 (IC50, 1.8 μM). Additional testing also identified it as an CCR5 antagonist (IC50, 0.9 μM), and it showed moderate in vitro HIV I inhibition. We demonstrated how machine learning can be used to identify molecules for repurposing as antagonists for G protein-coupled receptors such as CCR3, CCR4, and CCR5. Lapatinib may represent a new orally available chemical probe for these 3 receptors, and it provides a starting point for further chemical optimization for multiple diseases impacting human health. SIGNIFICANCE STATEMENT: We describe the building of machine learning models for the chemokine receptors CCR3, CCR4, and CCR5 trained on data from the ChEMBL database. Using these models, we identified lapatinib as a potent inhibitor of CCR3, CCR4, and CCR5. Our study illustrates the potential of machine learning in identifying molecules for repurposing as antagonists for G protein-coupled receptors, including CCR3, CCR4, and CCR5, which have various therapeutic applications.},
}
@article {pmid39918758,
year = {2025},
author = {Leung, EH and Yeh, S and Lampert, S},
title = {Favorable Outcome After Pegcetacoplan (Syfovre)-Associated Occlusive Retinal Vasculitis.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {3},
pages = {170-173},
doi = {10.3928/23258160-20241216-01},
pmid = {39918758},
issn = {2325-8179},
mesh = {Humans ; Female ; Aged, 80 and over ; *Retinal Vasculitis/chemically induced/drug therapy/diagnosis ; Intravitreal Injections ; Visual Acuity ; Anti-Bacterial Agents/therapeutic use ; Glucocorticoids/therapeutic use ; *Eye Infections, Bacterial/drug therapy/microbiology/diagnosis ; Fluorescein Angiography ; Geographic Atrophy/drug therapy ; *Staphylococcal Infections/drug therapy/microbiology/diagnosis ; },
abstract = {An 86-year-old woman with advanced dry age-related macular degeneration developed occlusive retinal vasculitis 11 days after her first pegcetacoplan injection. Vision decreased from 20/30 to counting fingers. Vision improved to 20/200 with periocular and systemic steroids. Two different sets of culture plates and gram stains were all negative, but one thioglycolate broth had a light growth of Staphylococcus epidermidis and repeat vitreous culture broth grew a different organism (Staphylococcus capitis). After intravitreal steroids and ceftazidime, the vision ultimately improved to 20/20. Periocular and systemic steroids and antibiotics were associated with a favorable visual outcome in this patient. [Ophthalmic Surg Lasers Imaging Retina 2025;56:170-173.].},
}
@article {pmid39918524,
year = {2025},
author = {Vemulakonda, GA and Bailey, ST and Kim, SJ and Kovach, JL and Lim, JI and Ying, GS and Flaxel, CJ and , },
title = {Age-Related Macular Degeneration Preferred Practice Pattern®.},
journal = {Ophthalmology},
volume = {132},
number = {4},
pages = {P1-P74},
doi = {10.1016/j.ophtha.2024.12.018},
pmid = {39918524},
issn = {1549-4713},
}
@article {pmid39918060,
year = {2025},
author = {Fulcher, C and Davey, C and Denniss, J},
title = {The quality, accuracy and appropriateness of UK optometric age-related macular degeneration referrals.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {3},
pages = {799-809},
pmid = {39918060},
issn = {1475-1313},
mesh = {Humans ; *Referral and Consultation/standards ; Female ; Male ; United Kingdom/epidemiology ; Retrospective Studies ; *Optometry/standards ; Aged ; Visual Acuity ; *COVID-19/epidemiology ; *Optometrists/standards ; SARS-CoV-2 ; *Wet Macular Degeneration/diagnosis/epidemiology ; Aged, 80 and over ; Middle Aged ; },
abstract = {PURPOSE: Little is known about the quality of optometrists' referrals to secondary care for neovascular age-related macular degeneration (nAMD), despite the need for timely intervention. We analysed the content and accuracy of optometrists' referrals for nAMD. Adherence to UK National Institute for Health and Care Excellence (NICE) guidelines and the impact of the COVID-19 pandemic were assessed as secondary measures.<br><br>METHODS: Optometric referrals to a specialist macular treatment centre in Bradford, United Kingdom, between March 2019 and March 2021 were retrospectively analysed and compared with subsequent electronic medical records. Data were extracted on legibility, reason for referral, patient and optometrist demographics, visual acuity, reported signs and symptoms, patient diagnosis and patient outcomes. Binomial logistic regression models were constructed to determine whether signs or symptoms noted in the referral were associated with subsequent nAMD diagnosis in secondary care and whether optometrist gender or experience influenced nAMD referral accuracy.<br><br>RESULTS: Across all 394 referrals analysed, 256 were for nAMD. Referral accuracy for nAMD was 39.8% (95% CI [34.0%, 45.9%]), with the most common reason for misdiagnosis being dry AMD. However, 76.8% of patients referred for suspected nAMD were either treated in secondary care or observed over multiple visits. 20% of suspected nAMD patients were seen within the NICE recommended 14-day window pre-COVID, dropping to 5% during the pandemic (p&#x2009;<&#x2009;0.001). Visual acuity was most strongly associated with nAMD diagnosis (&#x3c7;[2](1)&#x2009;=&#x2009;13.71, p&#x2009;<&#x2009;0.001) followed by macular haemorrhage (&#x3c7;[2](1)&#x2009;=&#x2009;5.89, p&#x2009;=&#x2009;0.02). Neither optometrist gender nor experience was significantly associated with confirmed nAMD. Legibility of referrals was 91-95% for patient details and 94-97% for the referring optometrist.<br><br>CONCLUSIONS: Although the overall quality and legibility of optometrists' macular referrals to secondary care were of a high standard, the diagnostic accuracy of nAMD was below 40%. Referred visual acuity was the main sign/symptom associated with confirmed nAMD diagnosis.},
}
@article {pmid39917144,
year = {2025},
author = {Allehyani, MH and Alsaeedi, AK and Alqthmi, RO and Saleh, RE and Alsamli, RS and Almalki, HA and Alshehri, AF and Felimban, SA and Kambiji, GJ and Almatrafi, MI and Othman, B},
title = {Comparative Efficacy of Brolucizumab and Aflibercept in Polypoidal Choroidal Vasculopathy: A Systematic Review and Meta-Analysis.},
journal = {Cureus},
volume = {17},
number = {1},
pages = {e77073},
pmid = {39917144},
issn = {2168-8184},
abstract = {Polypoidal choroidal vasculopathy (PCV) represents a distinct subtype of neovascular age-related macular degeneration (nAMD). PCV is currently managed using intravitreal anti-vascular endothelial growth factor (VEGF) agents such as brolucizumab and aflibercept. This meta-analysis compares the effectiveness of brolucizumab and aflibercept in PCV patients. We systematically searched four electronic databases to identify eligible studies. Data extraction and pooling were performed utilizing the mean difference (MD) or rate ratio (RR) through the generic inverse variance method, with significance determined by a p-value < 0.05 between intervention subgroups. The generic inverse variance analysis method was applied with the employment of the random-effect model when data were heterogeneous. We retrieved 44 studies, 35 were included in the meta-analysis. The analysis compared the efficacy of aflibercept and brolucizumab in patients with nAMD over 3-6 months and 12 months. For best-corrected visual acuity (BCVA), the MD between aflibercept and brolucizumab were -0.11 versus -0.06 at 3-6 months and -0.11 versus -0.04 at 12 months, with no substantial differences (p = 0.58 and p = 0.08, respectively). Regarding polypoidal regression, RR after aflibercept use was 53% versus 70% for brolucizumab at 3-6 months and 47% versus 61% at 12 months, with no significant differences (p = 0.19 and p = 0.31, respectively). In terms of central retinal thickness (CRT), the MDs for aflibercept versus brolucizumab were -129.03 versus -143.93 at 3-6 months and -129.72 versus -145.32 at 12 months, without significant differences (p = 0.62 for both). For central choroidal thickness (CCT) and central foveal thickness (CFT), no significant differences were found between the two interventions at either time point. However, for central macular thickness, brolucizumab demonstrated superiority over aflibercept at 12 months (MD = -119.29 versus -215.00, p < 0.0001). In conclusion, our meta-analysis comparing aflibercept and brolucizumab in PCV revealed no significant differences in BCVA, polypoidal regression, CRT, CCT, and CFT at 6 or 12 months. Overall, both drugs demonstrated comparable efficacy in managing PCV.},
}
@article {pmid39914136,
year = {2025},
author = {Lee, JL and Hsu, YA and Huang, YT and Chen, JJ and Wu, MY and Tsai, FJ and Lin, HJ and Huang, YH and Tien, PT and Wan, L},
title = {Endometriosis as a risk factor for age-related macular degeneration: A nationwide population-based study.},
journal = {Maturitas},
volume = {195},
number = {},
pages = {108211},
doi = {10.1016/j.maturitas.2025.108211},
pmid = {39914136},
issn = {1873-4111},
mesh = {Humans ; Female ; *Endometriosis/complications/epidemiology ; *Macular Degeneration/epidemiology/etiology ; Taiwan/epidemiology ; Risk Factors ; Middle Aged ; Incidence ; Adult ; Aged ; Databases, Factual ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Propensity Score ; },
abstract = {OBJECTIVE: Investigate the association between endometriosis and the incidence of age-related macular degeneration.<br><br>MATERIAL AND METHODS: This study used data from Taiwan's National Health Insurance Research Database (2000-2018) to examine the link between endometriosis and age-related macular degeneration. The endometriosis cohort included women diagnosed with the condition, with the index date set as their first diagnosis. A control group of women without endometriosis was matched using propensity score matching based on age, year of the index date, and comorbidities. The primary outcome was the occurrence of age-related macular degeneration during the study period. The incidence of age-related macular degeneration was compared between the two cohorts using a Cox regression model, and the risk of developing age-related macular degeneration was estimated with the Kaplan-Meier method.<br><br>RESULTS: The study included 53,993 individuals per group, with no significant differences in age or comorbidities. The mean follow-up duration was significantly longer for the endometriosis cohort (10.18&#xa0;years) than the non-endometriosis cohort (9.96&#xa0;years). Patients with endometriosis exhibited a significantly higher risk of age-related macular degeneration (adjusted hazard ratio&#xa0;=&#xa0;1.43, 95&#xa0;% confidence interval: 1.26-1.63, p&#xa0;<&#xa0;0.001) after adjusting for age and comorbidities. The Kaplan-Meier curves confirmed an increased cumulative incidence of age-related macular degeneration in the endometriosis cohort. Subgroup analysis revealed a higher risk of age-related macular degeneration in patients with endometriosis across various age groups and in those without comorbidities.<br><br>CONCLUSION: This study demonstrated a significant association between endometriosis and the risk of developing age-related macular degeneration in women.},
}
@article {pmid39913906,
year = {2024},
author = {Morgan, KR and Richards, PJ and Chang, JS},
title = {Systemic anti-VEGF biosimilar therapy associated with improved macular anatomy and duration of effect in a patient with nearly recalcitrant neovascular age-related macular degeneration.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001619},
pmid = {39913906},
issn = {1937-1578},
abstract = {PURPOSE: To present a patient with neovascular AMD treated systemically with the biosimilar bevacizumab-awwb (Mvasi) with superior SRF resolution when compared to continuous and repeated intravitreal treatments.<br><br>METHODS: Retrospective single case report.<br><br>RESULTS: After 3 years of monthly aflibercept treatment for nAMD, the patient had persistent subretinal fluid (SRF). Systemic bevacizumab-awwb (Mvasi) infusions were initiated by her oncologist for ovarian cancer and SRF resolved for the first time. After one additional aflibercept injection, and continued bevacizubam-awwb infusions for her cancer, SRF did not recur. Thirteen weeks later, at final follow-up before the patient passed away, the macula remained dry and no additonal intravitreal treatment was given.<br><br>CONCLUSION: When systemic anti-VEGF biosimilar therapy was administered, there was improved anatomy and prolonged duration of effect compared to the intravitreal therapy alone. Adverse systemic effects limit the routine use of systemic anti-VEGF therapy for retinal disease. However if a patient requires systemic anti-VEGF or anti-VEGF biosimilar therapy for malignancy, it may also benefit retinal disease leading to benefits in quality of life and fewer office visits.},
}
@article {pmid39913504,
year = {2025},
author = {Mehta, NN and Nagel, ID and Agnihotri, A and Heinke, A and Cheng, L and Bartsch, DU and Freeman, WR and Gomez, ML},
title = {Dry eye disease treatment improves subjective quality-of-life responses in patients with AMD, independent of disease stage.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0318733},
pmid = {39913504},
issn = {1932-6203},
support = {OT2 OD032644/OD/NIH HHS/United States ; P30 EY022589/EY/NEI NIH HHS/United States ; R01 EY016323/EY/NEI NIH HHS/United States ; R01 EY033847/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Quality of Life ; Male ; Female ; Aged ; *Dry Eye Syndromes/therapy/complications ; *Macular Degeneration/complications/pathology/therapy ; Surveys and Questionnaires ; Middle Aged ; Aged, 80 and over ; Treatment Outcome ; Severity of Illness Index ; },
abstract = {PURPOSE: To determine the impact of severity of age-related macular degeneration (AMD) on subjective treatment response in patients treated for dry eye disease.<br><br>METHODS: A total of 203 eyes diagnosed with evaporative dry eye disease (DED) due to meibomian gland dysfunction were treated using the LipiFlow or MiBoFlo systems. From this cohort, 40 eyes with stable dry AMD (early, intermediate, or late stages) were included. Each participant completed the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness Questionnaire (SPEED) before treatment and at a 6-month follow-up. Changes in questionnaire scores were analyzed using one-way analysis of variance (ANOVA) to assess differences between AMD severity groups.<br><br>RESULTS: Improvement in SPEED and OSDI scores, including vision related OSDI scores were observed across all AMD stages, with no significant differences between groups (p<0.05).<br><br>CONCLUSION: Managing DED improved quality of life (QOL) in patients with AMD, regardless of retinal disease severity. This highlights the importance of treating coexisting ocular surface conditions to enhance patient outcomes, even in the presence of significant maculopathy.},
}
@article {pmid39913124,
year = {2025},
author = {Yoshida, K and Anegondi, N and Pely, A and Zhang, M and Debraine, F and Ramesh, K and Steffen, V and Gao, SS and Cukras, C and Rabe, C and Ferrara, D and Spaide, RF and Sadda, SR and Holz, FG and Yang, Q},
title = {Deep Learning Approaches to Predict Geographic Atrophy Progression Using Three-Dimensional OCT Imaging.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {2},
pages = {11},
pmid = {39913124},
issn = {2164-2591},
mesh = {Aged ; Female ; Humans ; Male ; *Deep Learning ; Disease Progression ; *Geographic Atrophy/diagnostic imaging/pathology ; *Imaging, Three-Dimensional/methods ; Macular Degeneration ; Neural Networks, Computer ; *Tomography, Optical Coherence/methods ; Clinical Trials as Topic ; },
abstract = {PURPOSE: To evaluate the performance of various approaches of processing three-dimensional (3D) optical coherence tomography (OCT) images for deep learning models in predicting area and future growth rate of geographic atrophy (GA) lesions caused by age-related macular degeneration (AMD).<br><br>METHODS: The study used OCT volumes of GA patients/eyes from the lampalizumab clinical trials (NCT02247479, NCT02247531, NCT02479386); 1219 and 442 study eyes for model development and holdout performance evaluation, respectively. Four approaches were evaluated: (1) en-face intensity maps; (2) SLIVER-net; (3) a 3D convolutional neural network (CNN); and (4) en-face layer thickness and between-layer intensity maps from a segmentation model. The processed OCT images and maps served as input for CNN models to predict baseline GA lesion area size and annualized growth rate.<br><br>RESULTS: For the holdout dataset, the Pearson correlation coefficient squared (r2) in the GA growth rate prediction was comparable for all the evaluated approaches (0.33&#x223c;0.35). In baseline lesion size prediction, prediction performance was comparable (0.9&#x223c;0.91) except for the SLIVER-net (0.83). Prediction performance with only the thickness map of the ellipsoid zone (EZ) or retinal pigment epithelium (RPE) layer individually was inferior to using both. Addition of other layer thickness or intensity maps did not improve the prediction performance.<br><br>CONCLUSIONS: All explored approaches had comparable performance, which might have reached a plateau to predict GA growth rate. EZ and RPE layers appear to contain the majority of information related to the prediction.<br><br>TRANSLATIONAL RELEVANCE: Our study provides important insights on the utility of 3D OCT images for GA disease progression predictions.},
}
@article {pmid39912810,
year = {2025},
author = {Ko, JS and Mendelsohn, AB and Daniels, K and Gomez-Lumbreras, A and Marshall, J and McDermott, C and Pawloski, PA and Yee, GC and Lockhart, CM},
title = {Patient characteristics and use for bevacizumab in ophthalmology and oncology in a distributed research network.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {31},
number = {2},
pages = {157-166},
pmid = {39912810},
issn = {2376-1032},
mesh = {Humans ; *Bevacizumab/therapeutic use/adverse effects/administration &amp; dosage ; Female ; Retrospective Studies ; Middle Aged ; Male ; Aged ; *Biosimilar Pharmaceuticals/therapeutic use/adverse effects/administration &amp; dosage ; *Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; *Neoplasms/drug therapy ; Adult ; Off-Label Use ; United States ; Ophthalmology ; Cohort Studies ; Medical Oncology ; *Eye Diseases/drug therapy ; Databases, Factual ; },
abstract = {BACKGROUND: Although bevacizumab and its biosimilars are commonly used, there are limited real-world data on bevacizumab use in the United States, especially biosimilar bevacizumab used in ophthalmologic conditions.<br><br>OBJECTIVE: To evaluate use patterns and patient characteristics for the originator bevacizumab relative to its biosimilars for labeled and off-label oncology and ophthalmology conditions and characterize adverse events in patients using bevacizumab for oncologic indications.<br><br>METHODS: We conducted a retrospective cohort study with the Biologics and Biosimilars Collective Intelligence Consortium-distributed database to identify patients aged 21&#xa0;years and older who received bevacizumab between January 1, 2010, and June 30, 2021. Oncology indications included colon, lung, and gynecologic (cervical, uterine, and ovarian) cancers. Ophthalmologic indications included neovascular age-related macular degeneration (AMD), retinal vein occlusion (RVO), choroidal neovascularization (CNV), and proliferative diabetic retinopathy (PDR). We also captured patients' demographic and clinical characteristics.<br><br>RESULTS: Total bevacizumab product (originator and biosimilars) use increased over time for RVO, CNV, and PDR starting in 2015 but decreased for AMD after 2016. For ophthalmology, bevacizumab product users were primarily male (56.8%), had a mean age of 62.9&#xa0;years (SD&#x2009;=&#x2009;0.08), and had a mean Charlson/Elixhauser combined comorbidity score ranging from 0.7 (CNV) to 2.7 (PDR). Bevacizumab users for oncology indications were mostly female (61.8%), had a mean age of 62.9&#xa0;years (SD&#x2009;=&#x2009;12.2), and had a mean Charlson/Elixhauser combined comorbidity score of 7.4 (SD&#x2009;=&#x2009;3.0). Oncologic biosimilar product use increased over time between 2019 and 2020 as follows: colon cancer, 6.2% to 49.4%; lung cancer, 1.9% to 36.2%; and gynecologic cancer, 2.4% to 38.1%.<br><br>CONCLUSIONS: Bevacizumab product use increased across most indications during the study period. Use for biosimilars increased in later years relative to the originator once available on the market. Limited data are available on real-world biosimilar use in the United States; future research should include monitoring for use and adverse events of these products.},
}
@article {pmid39911676,
year = {2024},
author = {Zhang, YY and Hu, JY and Ling, Q and Xu, SH and Kang, M and Wei, H and Zou, J and Yi, Q and Tan, G and Shao, Y},
title = {The amplitude of low frequency fluctuation and spontaneous brain activity alterations in age-related macular degeneration.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1507971},
pmid = {39911676},
issn = {2296-858X},
abstract = {BACKGROUND: Wet age-related macular degeneration (wAMD) is a vision-threatening eye disease worldwide. The amplitude of low-frequency fluctuation (ALFF) method was used to observe changes in spontaneous brain activity, which may help to investigate the underlying pathological mechanism of AMD.<br><br>METHODS: Eighteen patients with wAMD and 18 age- and gender-matched healthy controls (HCs) were recruited. The ALFF method was used on each subject and mean ALFF values were compared between groups. The receiver operating characteristic (ROC) curve was used to compare the two groups.<br><br>RESULTS: ALFF values in the temporal lobe and limbic lobe/parahippocampal gyrus were significantly higher than controls, while values in the postcentral gyrus were significantly lower. The under the curve of the ROC (AUC) of the three regions shows high accuracy of the diagnosis.<br><br>CONCLUSION: The abnormal spontaneous brain activity of patients with AMD suggests scope for the use of ALFF in the diagnosis or prognosis in AMD.},
}
@article {pmid39911424,
year = {2025},
author = {Sun, H and Zhao, P and Zhao, L and Zhao, Z and Chen, H and Ren, C and Guo, B},
title = {Therapeutic applications of artemisinin in ophthalmic diseases.},
journal = {Heliyon},
volume = {11},
number = {2},
pages = {e42066},
pmid = {39911424},
issn = {2405-8440},
abstract = {Artemisinin is a sesquiterpene lactone extracted from the chrysanthemum plant, Artemisia annua. It is known for its curative effects in the treatment of pulmonary hypertension, leukemia, diabetes, malaria, and other diseases, owing to its abundant biological activity. In recent years, with the development of plant secondary metabolite research, other potential pharmacological effects of artemisinin-based drugs have received increasing attention; in particular, reports of their application for the potential treatment of ophthalmology-related diseases have gradually increased. Recently, studies confirmed that artemisinin plays therapeutic roles in eye diseases through regulation of signaling pathways, such asNrf2/HO-1/Keap1, TLR/MyD88/NF-κb, PI3K/AKT/mTOR, and FASN/Kmal-mTOR/SREBP1, and biological factors, such as protein kinase B, AMP-activated protein kinase, tumor necrosis factor alpha, nod-like receptor protein 3, vascular endothelial growth factor, malonyl-coenzyme A and cytochrome C. However, since ocular diseases are often caused by various factors, how artemisinin can play a good disease prevention role by modulating these factors needs to be further verified, and most of the current studies focus on in vitro and animal experiments, lacking sufficient information on clinical trial studies. To better explore and perfect the mechanism of action of artemisinin in ophthalmic diseases, and to better promote the clinical application of artemisinin, this study reviews the latest progress of artemisinin treatment for uveitis, uveal melanoma, age-related macular degeneration, diabetic retinopathy, ocular neovascularization, and dry eye, and it will provide theoretical support for the large-scale application of artemisinin in ophthalmic diseases in the future.},
}
@article {pmid39910679,
year = {2025},
author = {Han, G and Xuewu, G and Meng, Z and Yuejing, W and Yuchun, W and Keshuang, Z and Hongbo, Y},
title = {Therapeutic effect of dihydroartemisinin on Alzheimer's disease model mice with senile macular degeneration.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {81},
pmid = {39910679},
issn = {2047-783X},
support = {LH2021H122//Natural Science Foundation of Heilongjiang Province of China/ ; },
mesh = {Animals ; *Alzheimer Disease/drug therapy/pathology/metabolism ; Mice ; *Artemisinins/pharmacology/therapeutic use/chemistry ; Disease Models, Animal ; Molecular Docking Simulation ; Autophagy/drug effects ; Amyloid beta-Peptides/metabolism ; Male ; Maze Learning/drug effects ; Humans ; },
abstract = {OBJECTIVES: This study focuses on the preventive and therapeutic effects of Dihydroartemisinin (DHA) on Alzheimer's disease (AD) model mice and the effects of DHA and donepezil on amyloid β-protein deposition and autophagy in nerve cells.<br><br>METHODS: Six autophagy related targets were selected for molecular docking with DHA to predict the affinity between DHA and the target. The AD mouse model was established and treated with donepezil and DHA, respectively. Morris water maze was used to detect the spatial learning and memory ability of AD mice. Hematoxylin eosin (he) staining was used to observe the structural changes of cerebral cortical neurons and retina, and transmission electron microscope was used to observe the structural changes of mitochondria and synapses. Immunohistochemistry (IHC) and immunofluorescence staining were used to detect the deposition of amyloid beta protein. Western blot was used to detect the expression of apoptosis and autophagy related proteins in the brain tissue of mice in each group.<br><br>RESULTS: The results of molecular docking showed that the selected active compounds had good binding activity with the target. The binding energy between DHA and A&#x3b2;, Bcl-2, ATG5, LC3, Caspase3, LAMP1 is -5.7, -7.0, -5.8, -7.2, -6.9&#xa0;kcal/mol. The water maze test showed that compared with the wild type (WT) group, the spatial memory ability of AD model group mice (5&#xd7; FAD) was significantly decreased, and the search time (27.62&#x2009;&#xb1;&#x2009;6.51&#xa0;s vs. 282.80&#x2009;&#xb1;&#x2009;17.15&#xa0;s) and average path (106.30&#x2009;&#xb1;&#x2009;29.65&#xa0;cm vs. 993.20&#x2009;&#xb1;&#x2009;135.80&#xa0;cm) were significantly prolonged. The application of donepezil and DHA significantly shortened the exploration time and average path (donepezil: 116.10&#x2009;&#xb1;&#x2009;10.58&#xa0;s, 529.40&#x2009;&#xb1;&#x2009;106.00&#xa0;cm; DHA: 99.71&#x2009;&#xb1;&#x2009;14.22&#xa0;s, 373.30&#x2009;&#xb1;&#x2009;60.97&#xa0;cm). The path to find the platform in DHA treatment group was shorter than donepezil treatment group (P&#x2009;<&#x2009;0.05). HE staining showed that the arrangement of nerve cells in 5&#xd7; FAD mice was disordered, and IHC showed that amyloid &#x3b2;-protein deposition was obvious. DHA and donepezil could improve the damage of cerebral cortex structure and reduce the deposition of extracellular amyloid &#x3b2;-protein in AD mice. Transmission electron microscopy showed that DHA and donepezil could reduce mitochondrial vacuolation and synaptic edema. The above results showed that DHA treatment effect was better than donepezil. Compared with the conventional feeding group, autophagy and apoptosis related proteins B-cell lymphoma-2 (BCL2) and anti-thymocyte globulin (ATG) were significantly down regulated in the 5&#xd7; FAD group, and the expressions of BCL2 and ATG were increased after treatment with DHA and donepezil.<br><br>CONCLUSIONS: DHA combined with BCL2 and ATG protein, through promoting autophagy protein, can reduce the damage of cerebral cortex structure in AD mice, reduce the deposition of extracellular &#x3b2;-amyloid protein, and then improve the memory ability of AD model mice. DHA treatment is superior to donepezil monotherapy.},
}
@article {pmid39910651,
year = {2025},
author = {Riazi-Esfahani, H and Faghihi, H and Bazvand, F and Mehrabi Bahar, M and Khojasteh, H and Husein Ahmed, A and Faghihi, S and Fakhraie, A and Zamani, MH and Ghasemi, S and Asadi Khameneh, E and Khalili Pour, E},
title = {Predictive value of different baseline optical coherence tomography biomarkers for visual acuity changes in neovascular age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {12},
pmid = {39910651},
issn = {2056-9920},
abstract = {BACKGROUND: To evaluate baseline optical coherence tomography (OCT) biomarkers in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) and their correlation with visual acuity changes following intravitreal aflibercept injections.<br><br>METHODS: A retrospective analysis was conducted on treatment-na&#xef;ve nAMD patients. Baseline OCT biomarkers, including shallow irregular pigment epithelial detachment (SIPED), subretinal hyperreflective material, subretinal fluid, intraretinal fluid (IRF), hyperreflective foci, and subretinal drusenoid deposits, were assessed. Patients received bimonthly aflibercept injections after three loading doses. Visual acuity changes were evaluated at 3 and 12 months. The maximum height and width of the largest pigment epithelial detachment (PED) were also measured.<br><br>RESULTS: Among 89 eyes with nAMD, mean best-corrected visual acuity (BCVA) improved by 6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline to month 3, with sustained improvement through month 12. Baseline IRF was associated with poorer visual acuity improvement at month 12, with patients showing a mean improvement of 1.6&#x2009;&#xb1;&#x2009;18.2 ETDRS letters versus 11.1&#x2009;&#xb1;&#x2009;10 ETDRS letters in those without IRF (P&#x2009;=&#x2009;0.002). Multivariable analysis indicated SIPED was linked to lower visual gains at month 3 (P&#x2009;=&#x2009;0.025). The largest PED width correlated significantly with lower BCVA gains at months 3 (P&#x2009;=&#x2009;0.021) and 12 (P&#x2009;=&#x2009;0.043), suggesting its potential as a prognostic factor.<br><br>CONCLUSION: Baseline OCT biomarkers, including SIPED, IRF, and PED width, may predict visual acuity changes in nAMD patients treated with aflibercept, highlighting the need for individualized monitoring.<br><br>CLINICAL TRIAL NUMBER: Not applicable.},
}
@article {pmid39910281,
year = {2025},
author = {Terheyden, JH and Dunbar, HMP and Schmitz-Valckenberg, S and Behning, C and Martinho, C and Luhmann, UFO and Saßmannshausen, M and Lüning, A and Miliu, A and Aires, ID and Basile, PG and Batuca, J and Schmid, M and Moll, KP and Zakaria, N and Tufail, A and Binns, A and Crabb, DP and Leal, S and Finger, RP and Holz, FG and , },
title = {Validating candidate endpoints for intermediate age-related macular degeneration trials in a multi-centre setting-lessons from the MACUSTAR study.},
journal = {Eye (London, England)},
volume = {39},
number = {6},
pages = {1031-1039},
pmid = {39910281},
issn = {1476-5454},
support = {116076//Innovative Medicines Initiative (IMI)/ ; },
mesh = {Aged ; Female ; Humans ; Male ; Angiogenesis Inhibitors/therapeutic use ; Clinical Trials as Topic ; *Endpoint Determination ; *Macular Degeneration/diagnosis/drug therapy/physiopathology ; Prospective Studies ; Visual Acuity/physiology ; Multicenter Studies as Topic ; Observational Studies as Topic ; },
abstract = {For the conduct of future interventional age-related macular degeneration (AMD) trials, the availability of clinical study endpoints is key. However, no endpoints have been accepted by regulators for evaluation of treatment for intermediate (i) AMD, i.e. the AMD stage at highest risk of developing irreversible geographic atrophy or macular neovascularization. The European MACUSTAR consortium has recruited more than 700 individuals to develop and validate structural, functional and patient-reported endpoints, enabling future iAMD trials based on a prospective observational, multi-centre cohort study. Reliably assessing candidate endpoints in a setting that involves multiple clinical sites across countries comes with a plurality of challenges in the study set-up, quality of data, recruitment of participants and study conduct. Therefore, the MACUSTAR consortium has established a framework that successfully addresses these topics, provides relevant insights into the natural history of iAMD and its sub-phenotypes, and will open new regulatory pathways. The MACUSTAR study is registered on ClinicalTrials.gov under NCT03349801.},
}
@article {pmid39910178,
year = {2025},
author = {Deák, GG and Birner, K and Gerendas, BS and Mylonas, G and Weigert, G and Michl, M and Steiner, I and Schmidt-Erfurth, UM},
title = {Comparison of optical coherence tomography vs. fluorescein angiography-based macular neovascularization classifications in age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {4303},
pmid = {39910178},
issn = {2045-2322},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Female ; Aged ; Male ; *Macular Degeneration/diagnostic imaging/pathology/classification ; Aged, 80 and over ; *Choroidal Neovascularization/diagnostic imaging/classification ; Subretinal Fluid/diagnostic imaging ; Middle Aged ; },
abstract = {We aimed to compare fluorescein angiography (FA)-based classification of macular neovascularisation (MNV) with optical coherence tomography (OCT)-based classification, as well as examine differences in retinal fluid among OCT MNV types. We analyzed baseline FA and OCT images from 704 eyes of neovascular AMD patients across two multicenter trials, with grading conducted at the Vienna Reading Center. Using a validated AI tool (RetInSight Fluid Monitor Version 2), we localized and quantified retinal fluid. Kappa coefficients for agreement between FA and OCT MNV types were 0.58 [0.52; 0.64] (type 1/occult), 0.46 [0.38; 0.55] (type 2/classic), and 0.53 [0.44; 0.62] (type 3/RAP). Significant differences in the volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were noted among MNV types (p < 0.0001). Pairwise comparisons revealed significant differences in IRF volumes across all lesion types except type 2 versus mixed type, in SRF between type 3 and other types, and in PED between type 2 and other lesions. In conclusion, there was moderate agreement between FA and OCT classifications, and notable differences in fluid distribution among OCT types, suggesting potential for AI-guided MNV recognition in clinical settings.},
}
@article {pmid39909072,
year = {2025},
author = {Eastline, M and Said, S and Bosch, MM and Knecht-Bosch, P},
title = {Exit Strategy for Treatment of Neovascular Age-Related Macular Degeneration in a Real-World Setting: Wishful Thinking?.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {4},
pages = {398-404},
doi = {10.1055/a-2511-5899},
pmid = {39909072},
issn = {1439-3999},
mesh = {Humans ; Retrospective Studies ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Male ; Aged ; Female ; Intravitreal Injections ; Aged, 80 and over ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis ; Visual Acuity/drug effects ; Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Degeneration/drug therapy ; Middle Aged ; Recurrence ; },
abstract = {INTRODUCTION: To analyze our outcome for patients with neovascular age-related macular degeneration (nAMD) treated with aflibercept in a treat-and-extend regimen pursuing an exit strategy (with best possible adherence to the "Bern" exit criteria) over 6 years in a real-world setting. The primary objective of the study was to investigate the proportion of patients who were able to achieve and maintain treatment exit.<br><br>METHODS: This is a retrospective chart review study of treatment-na&#xef;ve patients diagnosed with nAMD receiving intravitreal aflibercept injections performed at our department with at least 2 years of follow-up visits. The primary outcome was the percentage of patients able to achieve and maintain the treatment exit regarding intravitreal anti-VEGF injections. Further outcome measures were best-corrected visual acuity (BCVA), incidence of recurrence after treatment cessation, duration of therapy, and number and intervals of injections.<br><br>RESULTS: There were 31 eyes of 25 patients included in this retrospective study. The observation period was from September 1, 2017 to August 31, 2023. Of all included patient eyes, 22.6% (n&#x2009;=&#x2009;7) reached exit criteria. Of all the "exit" patients, 28.6% (n&#x2009;=&#x2009;2) suffered from disease relapse and therapy was restarted at a mean (&#xb1;&#x2009;SD) of 41.5&#x2009;&#xb1;&#x2009;12.5 weeks (range: 29 to 54 weeks). Regarding the eyes that met treatment exit, 5 of 31 (16.1%) had no disease recurrence in the observed study period. The median BCVA (Snellen decimal; &#xb1; interquartile range: IQR) changed from 0.63 (0.27) at baseline to 0.63 (0.4) in the first year, 0.63 (0.3) in the second year, 0.63 (0.46) in the third year, 0.63 (0.3) in the fourth year, 0.63 (0.4) in the fifth year, and 0.4 (0.04) in the sixth year. The median number of injections (&#xb1; IQR) per eye in the first year of treatment was 8 (2), in the second year 5 (2), in the third year 5 (2.5), in the fourth year 5 (1), in the fifth year 3 (0.8), and in the sixth year 3 (0). Extension of the treatment interval after the loading phase in weeks was achieved up to a median (&#xb1;&#x2009;IQR) of 5.8 (4) in the first year, 8.4 (6) in the second year, 8 (5.7) in the third year, 9.4 (5.6) in the fourth year, 7 (6.9) in the fifth year, and 8.4 (3.1) in the sixth year of observation.<br><br>DISCUSSION: Our study indicates a lower rate of patients reaching exit criteria with a treat-and-extend regimen compared to clinical study settings, and a similar recurrence rate of nAMD after treatment cessation. Nonadherence to a strict treat-and-extend protocol might influence the result.},
}
@article {pmid39906411,
year = {2025},
author = {Larsen, PP and Dinet, V and Delcourt, C and Helmer, C and Linard, M},
title = {Could Infectious Agents Play a Role in the Onset of Age-related Macular Degeneration? A Scoping Review.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100668},
pmid = {39906411},
issn = {2666-9145},
abstract = {TOPIC: This scoping review aims to summarize the current state of knowledge on the potential involvement of infections in age-related macular degeneration (AMD).<br><br>CLINICAL RELEVANCE: Age-related macular degeneration is a multifactorial disease and the leading cause of vision loss among older adults in developed countries. Clarifying whether certain infections participate in its onset or progression seems essential, given the potential implications for treatment and prevention.<br><br>METHODS: Using the PubMed database, we searched for articles in English, published until June 1, 2023, whose title and/or abstract contained terms related to AMD and infections. All types of study design, infectious agents, AMD diagnostic methods, and AMD stages were considered. Articles dealing with the oral and gut microbiota were not included but we provide a brief summary of high-quality literature reviews recently published on the subject.<br><br>RESULTS: Two investigators independently screened the 868 articles obtained by our algorithm and the reference lists of selected studies. In total, 40 articles were included, among which 30 on human data, 9 animal studies, 6 in&#xa0;vitro experiments, and 1 hypothesis paper (sometimes with several data types in the same article). Of these, 27 studies were published after 2010, highlighting a growing interest in recent years. A wide range of infectious agents has been investigated, including various microbiota (nasal, pharyngeal), 8 bacteria, 6 viral species, and 1 yeast. Among them, most have been investigated anecdotally. Only Chlamydia pneumoniae, Cytomegalovirus, and hepatitis B virus received more attention with 17, 6, and 4 studies, respectively. Numerous potential pathophysiological mechanisms have been discussed, including (1) an indirect role of infectious agents (i.e. a role of infections located distant from the eye, mainly through their interactions with the immune system) and (2) a direct role of some infectious agents implying potential infection of various cells types within AMD-related tissues.<br><br>CONCLUSIONS: Overall, this review highlights the diversity of possible interactions between infectious agents and AMD and suggests avenues of research to enrich the data currently available, which provide an insufficient level of evidence to conclude whether or not infectious agents are involved in this pathology.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39905826,
year = {2025},
author = {Jo, S and Kim, YJ and Hwang, T and Jang, SY and Park, SJ and Ye, S and Jung, Y and Yoo, J},
title = {Injectable ultrathin porous membranes harnessing shape memory polymers for retinal tissue engineering.},
journal = {Journal of materials chemistry. B},
volume = {13},
number = {9},
pages = {3161-3172},
doi = {10.1039/d4tb02287d},
pmid = {39905826},
issn = {2050-7518},
mesh = {*Tissue Engineering ; Porosity ; Humans ; *Retinal Pigment Epithelium/cytology ; *Biocompatible Materials/chemistry ; Tissue Scaffolds/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Polyesters/chemistry ; Cell Line ; Surface Properties ; *Polymers/chemistry ; *Retina ; Membranes, Artificial ; Particle Size ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by the progressive degeneration of retinal cells, particularly retinal pigment epithelial (RPE) cells. Conventional treatments primarily focus on slowing disease progression without providing a cure. Recent advances in tissue engineering and cell-based therapies offer promising avenues for regenerating retinal tissue and restoring vision. In this study, we developed ultrathin, nanoporous membrane scaffolds designed to mimic Bruch's membrane (BrM) for RPE cell transplantation using vapor-induced phase separation. These scaffolds, fabricated from a blend of poly(L-lactide-co-ε-caprolactone) (PLCL) and poly(lactic-co-glycolic acid) (PLGA), exhibited favorable topography, biocompatibility, and shape-memory properties. In vitro experiments confirmed that the nanoporous topography effectively supports the formation of RPE monolayers with intact tight junctions. Additionally, the shape-memory characteristic enables the membrane to self-expand at body temperature (37 °C), facilitating minimally invasive delivery via injection. ARPE-19 cell-attached nanothin membranes successfully demonstrated shape-recovery properties and were deliverable through a catheter in an ex vivo model. Our findings suggest that the developed scaffolds provide a promising approach for retinal tissue engineering and could significantly contribute to advanced treatments for AMD and other retinal degenerative diseases.},
}
@article {pmid39905351,
year = {2025},
author = {Zeng, Y and Liu, Y and Chen, X and Kenny, J and Rong, R and Xia, X},
title = {Global, regional, and national burden of blindness and vision loss attributable to smoking from 1990 to 2021, and forecasts to 2030: findings from the Global Burden of Disease Study 2021.},
journal = {BMC public health},
volume = {25},
number = {1},
pages = {440},
pmid = {39905351},
issn = {1471-2458},
support = {BX20230434//China National Postdoctoral Program for Innovative Talents/ ; 2023M743952//China Postdoctoral Science Foundation/ ; 2023Q12//the Youth Science Foundation of Xiangya Hospital/ ; 82171058//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Blindness/epidemiology/etiology ; Male ; Female ; *Global Burden of Disease/trends ; Forecasting ; *Smoking/adverse effects/epidemiology ; Middle Aged ; Aged ; *Global Health/statistics &amp; numerical data ; Adult ; Aged, 80 and over ; *Cost of Illness ; Cataract/epidemiology ; Macular Degeneration/epidemiology ; Disability-Adjusted Life Years ; Young Adult ; },
abstract = {OBJECTIVE: This study aims to systematically elucidate the burden of blindness and vision loss (BVL) attributable to smoking from 1990 to 2021 and to forecast the trends in BVL burden over the next decade.<br><br>METHODS: We extracted data on years lived with disability (YLDs) and age-standardized YLDs rate (ASYR) related to blindness and vision loss (BVL) caused by smoking, including cataracts and age-related macular degeneration (AMD), from the Global Burden of Disease (GBD) database for the years 1990 to 2021. These data were disaggregated by age, gender, sociodemographic index (SDI), region, and country. Temporal trends in the burden of smoking-induced BVL were evaluated by calculating the average annual percentage changes (AAPCs).<br><br>RESULTS: BVL attributable to smoking presents a significant disease burden, with global BVL-related YLDs attributable to smoking increasing from 1990 to 2021, while ASYR showed a declining trend. In 2021, the global BVL-related YLDs and ASYR attributable to smoking were estimated at 284.03 thousand and 3.27 per 100,000 population. The ASYR for cataract and AMD are 2.60 and 0.68 per 100,000, respectively. The burden was notably higher in males than females, highlighting significant gender disparities. Regionally, the highest burdens were observed in South Asia, Southeast Asia, and North Africa. It is expected that the number of global BVL-related YLDs will increase further by 2030.<br><br>CONCLUSION: Smoking has imposed a substantial disease burden on BVL over the past three decades. The burden is predominantly concentrated among males, particularly older individuals and those in low to middle-SDI regions. Moreover, the burden of smoking-induced BVL is expected to continue improving over the next decade.},
}
@article {pmid39904976,
year = {2025},
author = {Jackson, VE and Wu, Y and Bonelli, R and Owen, JP and Scott, LW and Farashi, S and Kihara, Y and Gantner, ML and Egan, C and Williams, KM and Ansell, BRE and Tufail, A and Lee, AY and Bahlo, M},
title = {Multi-omic spatial effects on high-resolution AI-derived retinal thickness.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1317},
pmid = {39904976},
issn = {2041-1723},
support = {APP1195236//Department of Health | National Health and Medical Research Council (NHMRC)/ ; },
mesh = {Humans ; *Retina/diagnostic imaging/pathology/metabolism ; Tomography, Optical Coherence/methods ; Neural Networks, Computer ; Macular Degeneration/genetics/diagnostic imaging/pathology ; Male ; Female ; Diabetic Retinopathy/genetics/diagnostic imaging/pathology ; Middle Aged ; Biomarkers ; Macula Lutea/diagnostic imaging/pathology ; Multiomics ; },
abstract = {Retinal thickness is a marker of retinal health and more broadly, is seen as a promising biomarker for many systemic diseases. Retinal thickness measurements are procured from optical coherence tomography (OCT) as part of routine clinical eyecare. We processed the UK Biobank OCT images using a convolutional neural network to produce fine-scale retinal thickness measurements across > 29,000 points in the macula, the part of the retina responsible for human central vision. The macula is disproportionately affected by high disease burden retinal disorders such as age-related macular degeneration and diabetic retinopathy, which both involve metabolic dysregulation. Analysis of common genomic variants, metabolomic, blood and immune biomarkers, disease PheCodes and genetic scores across a fine-scale macular thickness grid, reveals multiple novel genetic loci including four on the X chromosome; retinal thinning associated with many systemic disorders including multiple sclerosis; and multiple associations to correlated metabolites that cluster spatially in the retina. We highlight parafoveal thickness to be particularly susceptible to systemic insults. These results demonstrate the gains in discovery power and resolution achievable with AI-leveraged analysis. Results are accessible using a bespoke web interface that gives full control to pursue findings.},
}
@article {pmid39904844,
year = {2025},
author = {Foss, AJE and Almeida, D and Cheung, CMG and Ogura, Y and de Cock, E and Empeslidis, T},
title = {To Treat or Not to Treat? Resolving the Question of Subretinal and Intraretinal Fluid in Age-Related Macular Degeneration: A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {3},
pages = {489-514},
pmid = {39904844},
issn = {2193-8245},
abstract = {Neovascular age-related macular degeneration (nAMD) is associated with considerable quality of life and economic burden. nAMD is characterized by pathological neovascularization, leading to the accumulation of retinal fluid. Intraretinal fluid (IRF) is a major contributor to vision loss and may predict response to treatment. In contrast, the role of subretinal fluid (SRF) is less clear. Nevertheless, complete resolution of retinal fluid accumulation is often stated to be a key goal of therapy for nAMD, even though some eyes may never achieve a fluid-free macula despite regular anti-vascular endothelial growth factor treatment. In this article, we review the current literature regarding the role of retinal fluid in nAMD disease outcomes and assess whether and when it may be beneficial to leave retinal fluid untreated. In this context, we highlight the importance of correctly identifying retinal fluid types in nAMD and avoiding confusion with other optical coherence tomography signs that may respond differently to therapy, such as subretinal pseudocysts. Current evidence shows that IRF is associated with poor outcomes and an increased risk of developing atrophy and fibrosis; resolution of this retinal fluid type should remain a treatment target. However, the literature around SRF indicates that low levels of this fluid type, potentially up to 150-200 µm in thickness, may be tolerated with minimal impact on vision, and that SRF could be protective against the development and progression of macular atrophy and fibrosis. Although mild SRF may be protective in nAMD, cause and effect between SRF and reduced or slowed atrophy has not yet been proven and requires further research. Treatment should be given for the most aggressive component; when both IRF and SRF are present, treatment should be given for IRF.},
}
@article {pmid39903912,
year = {2025},
author = {Safran, JP and Momenaei, B and Martin, J and Crain, B and Richards, C and Kaiser, R and Garg, SJ and Sivalingam, A and Spirn, M and Hsu, J},
title = {RHEGMATOGENOUS RETINAL DETACHMENT AFTER VITRECTOMY AND SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR FOR SUBMACULAR HEMORRHAGE.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {6},
pages = {1043-1049},
doi = {10.1097/IAE.0000000000004417},
pmid = {39903912},
issn = {1539-2864},
support = {//J. Arch McNamara, MD Fund for Retina Research and Education, Wills Eye Hospital, Philadelphia, PA./ ; },
mesh = {Humans ; *Vitrectomy/adverse effects ; *Retinal Detachment/etiology/epidemiology/diagnosis ; *Tissue Plasminogen Activator/administration &amp; dosage ; Male ; Female ; Retrospective Studies ; *Retinal Hemorrhage/diagnosis/surgery/therapy/drug therapy ; Visual Acuity ; Middle Aged ; Aged ; Fibrinolytic Agents/administration &amp; dosage ; Follow-Up Studies ; Incidence ; *Postoperative Complications ; },
abstract = {PURPOSE: To investigate the incidence and outcomes of rhegmatogenous retinal detachment (RRD) occurring after pars plana vitrectomy and subretinal tissue plasminogen activator for submacular hemorrhage (SMH).<br><br>METHODS: Charts were reviewed between April 1, 2014, and September 1, 2023, for eyes that underwent pars plana vitrectomy/subretinal tissue plasminogen activator for SMH.<br><br>RESULTS: Of 167 eyes, 15 eyes (9%) developed RRD with macular detachment in 12 eyes (80%) and proliferative vitreoretinopathy (PVR) in nine eyes (60%). The median (interquartile range, IQR) time from pars plana vitrectomy/subretinal tissue plasminogen activator until RRD diagnosis was 41 days (22-81). Thirteen eyes underwent RRD repair and two eyes were observed due to poor visual prognosis. Single-surgery anatomical success was achieved in 11 eyes (85%) at three months and nine eyes (70%) at the final visit. Four eyes (27%) developed redetachment, and three eyes underwent a median of two additional repairs. The final anatomical success rate for reattachment was 92% (12/13). The median (IQR) logarithm of the minimal angle of resolution [Snellen] visual acuity at the preoperative visit after SMH was 2 (2-2.3) [20/2,000], which worsened to 2.3 (2.2-2.7) [20/4,000] at the time of RRD diagnosis (P = 0.01) and plateaued by the final visit to 2.3 (2-2.7) [20/4,000] (P = 0.15).<br><br>CONCLUSION: Postoperative RRD occurred in nearly one in 10 eyes after pars plana vitrectomy/subretinal tissue plasminogen activator for SMH and was associated with a relatively high rate of PVR.},
}
@article {pmid39903180,
year = {2025},
author = {Futterknecht, S and Anders, P and Mai, J and Riedl, S and Hall, U and Gabrani, C and Pfau, K and Menten, MJ and Rueckert, D and Prevost, AT and Bogunovic, H and Fritsche, LG and Schmidt-Erfurth, U and Sivaprasad, S and Lotery, A and Scholl, HPN and Pfau, M},
title = {Targeted Microperimetry Grids for Focal Lesions in Intermediate AMD: PINNACLE Study Report 7.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {2},
pages = {6},
pmid = {39903180},
issn = {1552-5783},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Aged ; *Visual Field Tests/methods ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged, 80 and over ; *Visual Fields/physiology ; *Macular Degeneration/physiopathology/diagnosis ; Visual Acuity/physiology ; *Retina/physiopathology ; Feasibility Studies ; },
abstract = {PURPOSE: The purpose of this study was to evaluate the feasibility and utility of optical coherence tomography (OCT)-based, targeted microperimetry grids in assessing focal lesions in intermediate age-related macular degeneration (iAMD).<br><br>METHODS: The multicenter, prospective PINNACLE study enrolled 395 patients with iAMD aged 55 to 90 years across 12 international sites. Participants underwent imaging, including OCT and microperimetry, every 4 to 12 months over 3 years. Deep learning algorithms detected focal lesions and changes in OCT images, including drusen regression, EZ/IZ loss with hypertransmission, and subretinal fluid, guiding 5-point microperimetry targeted to lesion locations. Data were analyzed using linear mixed models to estimate differences between retinal sensitivity measured by the 5-point focal grids and sensitivity interpolated from the 24-point standard grids.<br><br>RESULTS: The final analysis included 93 eyes from 83 patients, assessing 605 of the 5-point targeted grids and standard grids across 235 focal lesions. The Pearson correlation between focally measured sensitivity and interpolated sensitivity was 0.76. However, interpolation from the standard grid could be erroneous, especially in central regions of lesions characterized by EZ/IZ loss with hypertransmission and subretinal fluid. Interpolation errors increased with distance to the nearest measurement point (slope = 2.20 dB per degree, 95% confidence interval [CI] = 1.52 to 2.87). A significant negative relationship was found between interpolation errors and retinal sensitivity, with the highest errors in areas of low sensitivity. Lesion size significantly impacted interpolation errors for EZ/IZ loss with hypertransmission (slope = -19.41 dB/mm&#xb2;, 95% CI = -29.63 to -9.18).<br><br>CONCLUSIONS: Targeted grids improved the detection and understanding of how focal retinal changes affect visual function in patients with iAMD, supporting the development of therapeutic interventions.},
}
@article {pmid39901612,
year = {2025},
author = {Thinggaard, BS and Subhi, Y and Grauslund, J and Stokholm, L},
title = {The impact of neovascular age-related macular degeneration on driving from a patient perspective.},
journal = {Acta ophthalmologica},
volume = {103},
number = {5},
pages = {e344-e345},
doi = {10.1111/aos.17448},
pmid = {39901612},
issn = {1755-3768},
}
@article {pmid39901532,
year = {2025},
author = {Parravano, M and Viola, F and Nicolò, M and Vujosevic, S and Bianchino, L and Sicari, E and Villa, G and Lanzetta, P},
title = {Real-world evidence of anti-VEGF therapies in patients with neovascular age-related macular degeneration in Italy: The RADIANCE study.},
journal = {European journal of ophthalmology},
volume = {35},
number = {4},
pages = {1366-1375},
pmid = {39901532},
issn = {1724-6016},
mesh = {Humans ; Retrospective Studies ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Male ; Female ; Italy/epidemiology ; *Visual Acuity/physiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Aged ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology/epidemiology ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Aged, 80 and over ; Follow-Up Studies ; Tomography, Optical Coherence ; Fluorescein Angiography ; Middle Aged ; },
abstract = {PurposeAge-related macular degeneration (AMD) is a leading cause of irreversible vision loss, particularly neovascular AMD (nAMD). This study aimed to investigate the real-world treatment patterns, effectiveness, and safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies for anti-VEGF naïve nAMD patients in Italy.MethodsRADIANCE is a retrospective, observational, multicenter cohort study conducted at 13 clinical sites across Italy. The study enrolled all consecutive patients with nAMD, naïve to any intraocular anti-VEGF treatment and who initiated therapy with aflibercept, ranibizumab, or bevacizumab between January 2017 and November 2018. The primary objective of this study was to evaluate changes in visual acuity (VA) 52 weeks after initiating treatment with anti-VEGF.ResultsA total of 405 patients were enrolled; of these, 263 patients had at least two VA measurements and were included in the completer analysis (CA) set. At 52 weeks, the median VA change from baseline in the CA set was +1 letter, with 41.1% showing ≥ 5-letter improvement. Stratified by anti-VEGF agent, no statistically significant differences were observed. Overall, patients received a median of 5.0 (25th-75th percentile 3-6) injections of the initial anti-VEGF agent during the first year. Patients receiving ≥ 6 injections in the first year showed better VA outcomes. Undertreatment was evident at decreasing injection frequency over time.ConclusionThe results of the RADIANCE study suggest an overall moderate effectiveness after 1 year of treatment with anti-VEGF in naïve patients with nAMD in Italy. Real-world outcomes demonstrated suboptimal treatment with no significant differences among anti-VEGF agents.},
}
@article {pmid39900480,
year = {2025},
author = {Patel, PJ},
title = {Treat and Extend Anti-VEGF Treatment Regimens for Neovascular Age-Related Macular Degeneration: To Stop or Not to Stop?.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {1},
pages = {8-10},
doi = {10.1111/ceo.14495},
pmid = {39900480},
issn = {1442-9071},
}
@article {pmid39900214,
year = {2025},
author = {Song, D and Wang, G and Liu, G and Zhang, C and Lv, B and Ni, Y and Xie, G},
title = {Age and gender-related changes in choroidal thickness: Insights from deep learning analysis of swept-source OCT images.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {52},
number = {},
pages = {104511},
doi = {10.1016/j.pdpdt.2025.104511},
pmid = {39900214},
issn = {1873-1597},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Deep Learning ; Female ; Male ; *Choroid/diagnostic imaging/anatomy &amp; histology ; Middle Aged ; Adult ; Aged ; Sex Factors ; Age Factors ; Aged, 80 and over ; },
abstract = {BACKGROUND: The choroid is a vital vascular layer of the eye, essential for maintaining ocular health. Understanding its structural variations, particularly choroidal thickness (CT), is crucial for the early detection of diseases, such as age-related macular degeneration (AMD), high myopia (HM), and diabetes mellitus (DM). Recent advancements in deep learning have significantly improved the segmentation and measurement of choroidal layers.<br><br>OBJECTIVE: This study aims to investigate age- and gender-related changes in CT and its components through deep learning analysis of swept-source optical coherence tomography (SS-OCT) images.<br><br>METHODS: A total of 262 participants (136 females and 126 males) were recruited from Peking University International Hospital. Exclusion criteria included ocular pathologies and systemic conditions. SS-OCT was utilized for CT, Sattler layer-choriocapillaris complex thickness (SLCCT), and Haller layer thickness (HLT) measurements. auto-measurement method, based on deep learning algorithms, ensured accuracy. Ethics approval and informed consent were obtained from all participants.<br><br>FINDINGS: Significant thinning of CT and SLCCT was observed after the age of 60, with HLT declining after the age of 30. Females exhibited marked thinning between the ages of 40 and 50, while males began to show thinning at age 60.<br><br>CONCLUSION AND IMPLICATIONS: This research highlights age-related changes in choroidal thickness, with a particular emphasis on gender differences. The findings suggest that females experience earlier thinning, potentially attributable to hormonal changes. Additionally, the study validates the efficiency of deep learning algorithms in measuring choroidal thickness, thereby enhancing the reliability of clinical practice.},
}
@article {pmid39900013,
year = {2025},
author = {Terheyden, JH and Holz, FG and Behning, C and Dunbar, HMP and Schmitz-Valckenberg, S and Tufail, A and Schmid, M and Crabb, DP and Saßmannshausen, M and Binns, A and Hoyng, CB and Zakaria, N and Poor, S and Moll, KP and Cosette, D and Martinho, C and Batuca, J and Cunha-Vaz, J and Luhmann, UFO and Leal, S and Finger, RP and , },
title = {The Spectrum of Functional, Structural, and Patient-Reported Outcomes in Intermediate Age-Related Macular Degeneration: A MACUSTAR Study Report.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {248},
number = {2},
pages = {101-111},
pmid = {39900013},
issn = {1423-0267},
mesh = {Humans ; *Visual Acuity ; *Tomography, Optical Coherence/methods ; Female ; *Patient Reported Outcome Measures ; Male ; Prospective Studies ; Aged ; *Macular Degeneration/physiopathology/diagnosis ; *Fluorescein Angiography/methods ; *Contrast Sensitivity/physiology ; Aged, 80 and over ; *Visual Fields/physiology ; *Macula Lutea/pathology ; Fundus Oculi ; Follow-Up Studies ; Middle Aged ; Dark Adaptation/physiology ; },
abstract = {INTRODUCTION: There is an unmet medical need for therapies in intermediate age-related macular degeneration (iAMD). The prospective European multicenter cohort study MACUSTAR validates structural, functional, and patient-reported iAMD endpoints for use in future trials. The multiplicity of assessments allows characterizing iAMD in more dimensions than previously available. We describe the heterogeneity of assessments in the iAMD baseline cohort of the MACUSTAR study.<br><br>METHODS: A wide range of assessments was administered across 20 European study sites in accordance with established guidelines. These assessments encompassed multiple structural evaluations, such as color fundus photography, fundus autofluorescence, and optical coherence tomography. Additionally, functional tests were conducted, including assessments of best-corrected and low-luminance visual acuity (VA), Moorfields acuity, contrast sensitivity, reading speed, mesopic and scotopic microperimetry, and dark adaptometry. Moreover, patient-reported outcome assessments, specifically the Vision Impairment in Low Luminance questionnaire, were also incorporated into the evaluation process. Associations between variables were investigated using Phi coefficients, Pearson correlation coefficients and age-corrected regression models.<br><br>RESULTS: Five-hundred eighty-five individuals with iAMD (66% women; mean (standard deviation) age: 72 &#xb1; 7 years) were included in the MACUSTAR study. Forty-nine percent had pigmentary abnormalities, 27% had reticular pseudodrusen; 10% and 9% had incomplete and complete retinal pigment epithelium and outer retinal atrophy at baseline, respectively. Mean best-corrected VA, low-luminance VA and mesopic average threshold on microperimetry at baseline were 0.03 &#xb1; 0.11 logMAR, 0.24 &#xb1; 0.16 logMAR, and 23.3 &#xb1; 3.7 dB. Mean Vision Impairment in Low Luminance (VILL) subscale scores at baseline were 2 &#xb1; 2 to 2 &#xb1; 3 logits. Phi coefficients between structural assessments ranged between 0.17 and 0.22 (median 0.21); correlation coefficients between function tests ranged between 0.07 and 0.69 (median 0.34) and between VILL scores ranged between 0.21 and 0.68 (median 0.23).<br><br>CONCLUSION: The findings from this broad and comprehensive spectrum of assessments of structure, function, and patient-reported outcomes in iAMD suggest that the disease spectrum is diverse and heterogeneous and that further efforts are necessary to fully understand and characterize iAMD in all its complexities. A further in-depth characterization will enable novel enrichment strategies for clinical trials in iAMD.},
}
@article {pmid39899265,
year = {2025},
author = {Turan, L and Arnold-Vangsted, A and la Cour, M and Hodzic-Hadzibegovic, D and Hajari, JN and Klefter, ON and Schneider, M and Subhi, Y},
title = {Treatment Interval Progression and Adherence to Observe-and-Plan Regimen for Neovascular Age-Related Macular Degeneration Treated with Aflibercept 2 mg.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {3},
pages = {585-597},
pmid = {39899265},
issn = {2193-8245},
abstract = {INTRODUCTION: Treatment burden of anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD) can be reduced with the Observe-and-Plan (O&amp;P) regimen, which allows for an individualized treatment while reducing the number of injections and assessment visits. In this study, we evaluate detailed characteristics of treatment interval adjustment through individual follow-ups and evaluate adherence to the O&amp;P regimen in a real-world setting in one of the largest centers in Europe.<br><br>METHODS: This was a retrospective cohort study of treatment-na&#xef;ve eyes with neovascular AMD that were treated with intravitreal aflibercept 2&#xa0;mg in an O&amp;P regimen who had persisting exudation after completion of loading dose. We evaluated decisions on adjustment of treatment intervals and adherence to the O&amp;P regimen from a total of 5 follow-up visits. Data from visits and decision on treatment intervals were extracted from a treatment database.<br><br>RESULTS: A total of 561 eyes were eligible for this study. Treatment intervals gradually increased from a 4-weeks interval (loading dose) to a wide distribution of intervals from 4-weeks to 12-weeks, and at the 5th follow-up 24.9% were followed without any treatment. In total, 209 eyes (49.5%) at the 5th follow-up (of 422 eyes present at the 5th follow-up) adhered to the treatment algorithm.<br><br>CONCLUSION: Aflibercept 2&#xa0;mg in an O&amp;P treatment regimen leads to a variety of treatment intervals, and some eyes may be overtreated. An important proportion of eyes deviate from the intended O&amp;P treatment regimen. Our study contributes to understanding real-world implications of personalized treatment regimens.},
}
@article {pmid39896424,
year = {2025},
author = {Lishinsky-Fischer, N and Chowers, I and Shwartz, Y and Levy, J},
title = {Patients with Age-related Macular Degeneration Have Increased Susceptibility to Valvular Heart Disease.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100677},
pmid = {39896424},
issn = {2666-9145},
abstract = {PURPOSE: Valvular heart disease (VHD) contributes significantly to cardiovascular-related morbidity worldwide. Aortic valve stenosis is the third most common cardiovascular disease in the Western world, after hypertension and coronary artery disease. Recent studies have reported an association between VHD and the presence of subretinal drusenoid deposits (SDDs), a distinct manifestation of age-related macular degeneration (AMD). However, these findings were based on self-reported questionnaires and relatively modest cohort sizes. Our goal was therefore to investigate the putative associations between AMD and VHD and between the presence of SDDs and VHD.<br><br>DESIGN: Retrospective case-control study.<br><br>SUBJECTS: A total of 945 with AMD and 8275 control patients without AMD from a single tertiary center.<br><br>METHODS: All patients with AMD underwent spectral-domain OCT (SD-OCT). The SD-OCT scans were annotated by 2 experienced graders. Among the patients with AMD, 547 had drusen and SDDs, and 398 had drusen only with no SDDs. We also extracted data from all 9220 patients' electronic medical records, including demographics and previous heart valve procedures based on International Classification of Diseases, ninth revision codes.<br><br>MAIN OUTCOME MEASURES: Heart valve-related diagnoses and procedures performed in both patient groups.<br><br>RESULTS: Patients with AMD had a higher prevalence of various VHDs compared with the control group, including increased rates of aortic stenosis (odds ratio [OR], 2.00; 95% confidence interval (CI), 1.40-2.86; P&#xa0;<&#xa0;0.001), aortic regurgitation (OR, 2.41; 95% CI, 1.49-3.91; P < 0.001), and mitral valve regurgitation (OR, 1.51; 95% CI, 1.13-2.01; P&#xa0;= 0.004). Heart valve procedures were also more prevalent among AMD patients including aortic valve replacement (OR, 1.70; 95% CI, 1.08-2.66; P&#xa0;= 0.019) and tricuspid valve replacement (OR, 3.99; 95% CI, 1.03-15.46; P&#xa0;= 0.03). Moreover, a supervised machine learning model successfully detected the presence of AMD based solemnly on the patient's history of VHD. In the AMD cohort, we found no significant difference in VHD prevalence between patients with nonneovascular AMD and patients with neovascular AMD, or between patients with SDDs and patients without SDDs.<br><br>CONCLUSIONS: Patients with AMD have a higher prevalence of VHD and are more likely to undergo a heart valve-related procedure compared with patients without AMD, with no difference between patients with SDDs and patients without SDDs in the AMD cohort.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39895321,
year = {2025},
author = {Sadikan, MZ and Lambuk, L and Reshidan, NH and Abdul Ghani, NA and Ahmad, AI and Ahmad Kamal, MS and Lazaldin, MAM and Ahmad Hairi, H and Mohamud, R and Abdul Nasir, NA},
title = {Age-Related Macular Degeneration Pathophysiology and Therapeutic Potential of Tocotrienols: An Update.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {41},
number = {3},
pages = {150-161},
doi = {10.1089/jop.2024.0123},
pmid = {39895321},
issn = {1557-7732},
mesh = {Humans ; *Macular Degeneration/drug therapy/physiopathology ; *Tocotrienols/therapeutic use/pharmacology ; *Antioxidants/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Animals ; },
abstract = {Age-related macular degeneration (AMD) poses a significant threat to visual health among the elderly, necessitating urgent preventive measures as the global population ages. Extensive research has implicated oxidative stress (OS)-induced retinal damage as a primary contributor to AMD pathogenesis, prompting investigations into potential therapeutic interventions. Among the various nutrients studied for their potential in AMD risk reduction, antioxidants have shown promise, with initial findings from the Age-Related Eye Disease Study suggesting a correlation between antioxidant supplementation and decreased AMD progression. This article explores the scientific foundation supporting the therapeutic efficacy of tocotrienol-rich fraction (TRF) as a viable candidate for slowing AMD progression, based on interventional studies. AMD is characterized by OS, inflammation, dysregulated lipid metabolism, and angiogenesis, all of which TRF purportedly addresses through its potent anti-inflammatory, lipid-lowering, antiangiogenic, and antioxidant properties. The review underscores TRF's promising attributes, aiming to deepen understanding of AMD pathogenesis and advocate for TRF-based pharmacological interventions to enhance therapeutic outcomes. Given the pressing need for effective AMD treatments, TRF represents a promising avenue for intervention, offering hope for improved vision outcomes and enhanced quality of life for individuals affected by this debilitating condition.},
}
@article {pmid39895155,
year = {2025},
author = {Lv, X and Shen, J and Du, X and Yue, B and Zhang, Q and Chang, W and Miao, Y and Ji, Z and Chen, L and Gong, Y and Yang, Y and Chen, Q},
title = {The Optimized Lipid-Modified Prodrug for CNV Treatment.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {37},
number = {10},
pages = {e2419263},
doi = {10.1002/adma.202419263},
pmid = {39895155},
issn = {1521-4095},
support = {52450010//National Natural Science Foundation of China/ ; 52325106//National Natural Science Foundation of China/ ; 52271248//National Natural Science Foundation of China/ ; BK20240040//Natural Science Foundation of Jiangsu Province/ ; //Collaborative Innovation Center of Suzhou Nano Science and Technology/ ; //Suzhou Key Laboratory of Nanotechnology and Biomedicine/ ; //111 Program from the Ministry of Education of China/ ; 2020YFA0211100//National Key Clinical Specialty Discipline Construction Program of China/ ; 2022YFA1206500//National Key Clinical Specialty Discipline Construction Program of China/ ; },
mesh = {*Prodrugs/chemistry/therapeutic use/pharmacology ; Animals ; Mice ; *Choroidal Neovascularization/drug therapy/pathology ; *Lipids/chemistry ; Humans ; Nanoparticles/chemistry ; *Angiogenesis Inhibitors/chemistry/therapeutic use/pharmacology ; Mice, Inbred C57BL ; },
abstract = {Choroidal neovascularization (CNV) is a prevalent cause of vision impairment. The primary treatment for CNV involves intravitreal injections of anti-vascular endothelial growth factor antibodies. Nevertheless, this approach still faces numerous limitations like poor patient compliance, high therapy expenditure and lack of response in some individuals. Herein, a series of anti-neovascularization prodrugs, SU5402 (SU), modified with lipids of varying chain lengths (C12, C16, C20, C24, C28) is synthesized (SU-C12, SU-C16, SU-C20, SU-C24, SU-C28). 1% polyvinyl alcohol (PVA) is used as a stabilizer to create nanoformulations of five prodrugs named SU-C12 NPs, SU-C16 NPs, SU-C20 NPs, SU-C24 NPs, SU-C28 NPs. Among these, SU-C20 NPs significantly prolong the retention of bioactive drug in the eye for up to 70 d. Moreover, SU-C20 NPs demonstrate superior tissue permeability via enhanced cellular endocytosis and exocytosis. With its prolonged retention and improved penetration, SU-C20 NPs reduce the fluorescence intensity of fundus leakage by 42.5% and the fluorescence area by 51.5% in CNV mice after four weeks, effectively inhibiting the progression of CNV. Altogether, small molecule drug SU is innovatively modified to improve its effectiveness for treating fundus neovascular diseases, proposing an alternative therapy for wet age-related macular degeneration (wAMD).},
}
@article {pmid39894426,
year = {2025},
author = {Yoo, K and Wu, L and Toy, B and Xu, BY},
title = {Relationship Between Chronic Stress Measured by Allostatic Load and Age-Related Macular Degeneration in the All of Us Research Program.},
journal = {American journal of ophthalmology},
volume = {272},
number = {},
pages = {150-160},
pmid = {39894426},
issn = {1879-1891},
support = {K23 EY029763/EY/NEI NIH HHS/United States ; R01 EY035677/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *Allostasis/physiology ; Retrospective Studies ; Aged ; *Macular Degeneration/physiopathology/epidemiology/etiology ; United States/epidemiology ; Biomarkers/blood ; Case-Control Studies ; Middle Aged ; Risk Factors ; Chronic Disease ; Blood Pressure/physiology ; Aged, 80 and over ; *Stress, Psychological/physiopathology ; C-Reactive Protein/metabolism ; },
abstract = {PURPOSE: To assess the longitudinal relationship between age-related macular degeneration (AMD) and allostatic load (AL), an established framework for quantifying the physiologic effects of chronic stress through measurements of systemic biomarkers.<br><br>DESIGN: Retrospective case-control study.<br><br>METHODS: Participants of the National Institutes of Health All of Us (AoU) Research Program with complete AL biomarker data between February 1985 to May 2022 and with (cases) or without (controls) AMD were identified. AL scores were calculated using the adapted Seeman AL scale consisting of 10 systemic biomarkers: body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, glomerular filtration rate, albumin, C-reactive protein, and homocysteine. AL score was defined as the number of biomarkers with measurements in the highest risk quartiles. Age was calculated as the median age at time of earliest or latest biomarker measurements. The main outcome was AMD status (AMD or non-AMD). Logistic regression models assessed the association between AL score and AMD after standardization of age and sex and adjustment for race/ethnicity and pack-years of cigarette smoking. Mediation analysis estimated the relationship between race/ethnicity and AMD as mediated by AL score.<br><br>RESULTS: Among 1530 participants (221 cases, 1309 controls) with complete biomarker data, there were 44.6% males, 76.1% non-Hispanic Whites (NHWs), 18.6% other specified race/ethnicity (Asian, Black, or Hispanic race/ethnicity), and 5.3% unspecified race/ethnicity. AL scores measured a median of 9.0 (IQR=5.0-14.0) years prior to diagnosis were higher among cases compared to controls (Median [IQR] = 2 [2-4] versus 2 [1-3]; P = .02). On multivariable analysis, higher baseline AL score (OR=1.11) and greater pack-years (OR=1.15 per 10 pack-years) conferred higher risk of AMD (P &#x2264; .02). Mediation analysis revealed a significant indirect effect that increased risk of AMD among other specified race/ethnicity participants compared to NHW participants through higher AL score (OR=1.07 per unit [1.01-1.15]).<br><br>CONCLUSION: All of Us participants diagnosed with AMD had greater AL score 9.0 years prior to AMD diagnosis. Chronic stress appears to increase risk for AMD and may contribute to racial/ethnic differences in disease prevalence.},
}
@article {pmid39894400,
year = {2025},
author = {Ortega, CM and Pratto, D},
title = {Degenerative lamellar foramen post drusenoid detachment of the retinal pigment epithelium.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {100},
number = {3},
pages = {150-153},
doi = {10.1016/j.oftale.2025.01.005},
pmid = {39894400},
issn = {2173-5794},
mesh = {Humans ; Middle Aged ; *Retinal Drusen/complications/diagnostic imaging ; *Retinal Detachment/etiology/diagnostic imaging ; Tomography, Optical Coherence ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Male ; *Macular Degeneration/complications ; *Retinal Perforations/etiology ; },
abstract = {The macular hole is a prevalent pathology whose types and causes are due to various reasons. Sometimes it can coexist with other diseases such as age-related macular degeneration. Its pathophysiological basis may have a common relationship with the degenerative lamellar foramen. Optical coherence tomography plays a fundamental role in understanding its genesis. In this work, we present the case of a 60-year-old patient with age-related macular degeneration, who consults due to decreased visual acuity in the left eye. The ophthalmological examination revealed a drusenoid detachment of the retinal pigment epithelium in the foveal area, visible by optical coherence tomography, in addition to multiple drusen in both eyes. Image follow-up showed regression of the detachment at the end of 60 days with the formation of a lamellar hole in its place. A follow-up was done for 24 months.},
}
@article {pmid39893955,
year = {2025},
author = {McCaleb, ML and Hughes, SG and Grossman, TR and Frazer-Abel, A and Jung, B and Yin, L and Henry, SP and Monia, BP and Schneider, E and Geary, R and Brice, GT},
title = {Inhibiting the alternative pathway of complement by reducing systemic complement factor B: Randomized, double-blind, placebo-controlled phase 1 studies with Sefaxersen.},
journal = {Immunobiology},
volume = {230},
number = {2},
pages = {152876},
doi = {10.1016/j.imbio.2025.152876},
pmid = {39893955},
issn = {1878-3279},
mesh = {Humans ; Male ; *Complement Factor B/metabolism/genetics/antagonists &amp; inhibitors ; Adult ; Double-Blind Method ; Female ; *Complement Pathway, Alternative/drug effects ; Middle Aged ; *Oligonucleotides, Antisense/administration &amp; dosage/adverse effects ; Young Adult ; *Thionucleotides/administration &amp; dosage/adverse effects ; },
abstract = {An over-active alternative complement pathway has been implicated in the pathophysiology of multiple diseases, including IgA nephropathy and geographic atrophy secondary to age related macular degeneration. In first-in-human double-blind, placebo-controlled phase 1 studies, the safety and pharmacodynamic effects of sefaxersen (RO7434656), a GalNAc-conjugated 2'-MOE antisense oligonucleotide targeting the complement factor B mRNA, was investigated. Healthy volunteers received either single or repeated (for 6 weeks) subcutaneous administrations of investigational drug or placebo. Safety and plasma complement protein levels were assessed throughout the studies and during 90-day follow-up periods. All subjects (54) completed the studies and no safety signals or clinically meaningful changes in blood chemistry, urinalysis, hematology, ECG, vital signs or ocular endpoints were observed. Mean levels of systemic complement factor B (FB) were reduced up to 38 % after single administration and 69 % after repeated administration. Lowering of FB protein was paralleled by similar reductions of plasma Bb levels. There was a strong correlation between reduction of plasma levels of FB and alternative complement pathway activity (AH50), but no meaningful changes in classical complement pathway activity (CH50). The long duration of lowering of FB levels following the last dose supports monthly dosing in future clinical trials. These clinical results support the ongoing Phase 2 development for geographic atrophy secondary to age-related macular degeneration and Ph 2/3 development for IgA nephropathy.},
}
@article {pmid39892803,
year = {2025},
author = {Linton, EF and Ahmad, NU and Filister, R and Wang, JK and Sohn, EH and Kardon, RH},
title = {Laser Speckle Flowgraphy Reveals Widespread Reductions in Ocular Blood Flow in nonexudative Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {273},
number = {},
pages = {92-106},
pmid = {39892803},
issn = {1879-1891},
support = {I01 RX000889/RX/RRD VA/United States ; IK1 RX005029/RX/RRD VA/United States ; R01 EY035435/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Choroid/blood supply ; Aged ; *Regional Blood Flow/physiology ; Case-Control Studies ; Laser-Doppler Flowmetry ; Blood Flow Velocity/physiology ; *Retinal Vessels/physiology/physiopathology ; Middle Aged ; Aged, 80 and over ; Intraocular Pressure/physiology ; Blood Pressure/physiology ; *Macular Degeneration/physiopathology ; *Geographic Atrophy/physiopathology ; Tomography, Optical Coherence ; Fluorescein Angiography ; },
abstract = {PURPOSE: To evaluate whether and where laser speckle flowgraphy (LSFG)-derived indices of ocular blood flow are reduced in non-exudative age-related macular degeneration (AMD) compared with age-matched control subjects.<br><br>DESIGN: Retrospective case-control study.<br><br>METHODS: Subjects with nonexudative AMD in the early, intermediate, or advanced stage underwent blood flow imaging with LSFG and were compared to age-matched control subjects. 39 eyes of 24 subjects with AMD and 41 eyes of 21 healthy controls were included. Mixed-effects models accounted for correlations between eyes in the same patient. Logistic regression evaluated the effect of ocular perfusion pressure and other factors associated with blood flow. Blood flow data was analyzed in 2 ways: by binary threshold for the primary analysis and through a superpixel-based method to map the territory of very low flow. The main outcome measure was choroidal blood flow and inner retinal blood flow in AMD and control eyes.<br><br>RESULTS: Choroidal blood flow as measured by the LSFG in arbitrary units (AU) was reduced by 33% in AMD patients vs controls (5.3 &#xb1; 0.3 AU vs 7.9 &#xb1; 0.5 AU respectively, P = .00005). Inner retinal blood flow was also significantly reduced in AMD (12.5 &#xb1; 0.6 vs 15.6 &#xb1; 0.5 AU, P = .004). Ocular perfusion pressure showed no significant difference between AMD and control groups (50&#xb1;5.5 vs 53&#xb1;6.7 mm Hg respectively, P = .17), indicating that neither elevated intraocular pressure nor low blood pressure could account for the reduced blood flow. In most cases, the area of lowest blood flow was large and diffuse, exceeding the abnormal area affected by non-exudative AMD. Controlling for other subject and eye characteristics, an eye with 10%, 25%, or 50% below the average normal choroidal blood flow was more likely to have AMD, with an odds ratio of 2.27, 7.76, and 60.1, respectively (P = .026).<br><br>CONCLUSIONS: Laser speckle flowgraphy showed lower choroidal and inner retinal blood flow in non-exudative AMD patients compared to age-matched controls, not explained by low perfusion pressure. Areas of reduced blood flow greatly exceeded the territory of choroidal atrophy, emphasizing its role as a risk factor for the development and potential progression of dry AMD.},
}
@article {pmid39891276,
year = {2025},
author = {Wang, X and Zhang, C and Jiang, H},
title = {Association of dietary inflammatory index with ocular diseases: a population-based cross-sectional study.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {62},
pmid = {39891276},
issn = {2047-783X},
mesh = {Humans ; Female ; Cross-Sectional Studies ; Male ; Middle Aged ; *Eye Diseases/epidemiology/etiology ; *Inflammation/epidemiology ; Nutrition Surveys ; *Diet/adverse effects ; Aged ; Adult ; Risk Factors ; Diabetic Retinopathy/epidemiology ; Cataract/epidemiology ; },
abstract = {BACKGROUND: Our research was designed to investigate the relationship between dietary inflammatory index (DII) and risk of ocular diseases, including glaucoma, cataract, age-related macular degeneration (ARMD), and diabetic retinopathy.<br><br>METHODS: We used the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2008 to conduct this study. The correlation between DII and risk of ocular diseases was examined using weighted multivariable logistic regression analysis, restricted cubic spline (RCS) plots, and subgroup analysis.<br><br>RESULTS: In total, 2885 participants from the NHANES database were included. The DII scores were divided into four group: Q1 (-&#xa0;4.438-0.386), Q2 (0.387-1.848), Q3 (1.849-3.073), and Q4 (3.074-4.970). RCS shown that there was a U-shaped correlation between DII and prevalence of glaucoma, cataract, ARMD, and diabetic retinopathy. After adjusting for underlying confounding variables, compared to Q1 group, the odd ratios (ORs) with 95 percent confidence intervals (CIs) for glaucoma, cataract, ARMD, and diabetic retinopathy across the quartiles were [0.97 (0.54, 1.75), 1.20 (0.68, 2.11), and 1.29 (0.73, 2.30)], [0.87 (0.56, 1.35), 1.12 (0.73, 1.73), and 1.16 (0.75, 1.80)], [0.85 (0.53, 1.36), 0.66 (0.40, 1.09), and 0.97 (0.61, 1.56)] and [0.86 (0.63, 1.18), 0.89 (0.65, 1.22), and 1.04 (0.75, 1.45)] for DII, respectively.<br><br>CONCLUSIONS: Reducing the intake of pro-inflammatory foods may be an effective measure to prevent the onset of ocular disease, including glaucoma, cataract, ARMD, and diabetic retinopathy. However, eating only anti-inflammatory foods is not the best choice.},
}
@article {pmid39890430,
year = {2025},
author = {Yuan, L and Kang, D and Teng, L and Chen, N and Zhan, J and Yu, R and Wang, Y and Lu, B},
title = {Biosafety and Efficacy Studies of Colchicine-Encapsulated Liposomes for Ocular Inflammatory Diseases.},
journal = {Journal of biomedical materials research. Part B, Applied biomaterials},
volume = {113},
number = {2},
pages = {e35540},
doi = {10.1002/jbm.b.35540},
pmid = {39890430},
issn = {1552-4981},
mesh = {Liposomes/chemistry ; Humans ; *Colchicine/pharmacology/chemistry ; *Retinal Pigment Epithelium/metabolism/pathology ; *Anti-Inflammatory Agents/pharmacology/chemistry ; *Inflammation/drug therapy/metabolism/pathology ; Macrophages/metabolism/pathology ; Reactive Oxygen Species/metabolism ; Monocytes/metabolism/pathology ; },
abstract = {Inflammation is a critical component in the progression of various ocular diseases, such as age-related macular degeneration, diabetic retinopathy, and uveitis, leading to significant vision loss. Colchicine has been used for treating gout with its anti-inflammatory effect. However, free colchicine demonstrated cytotoxicity to ocular cells and cannot directly be used for eye disease. Thus, this study introduces, for the first time, the development and use of colchicine-encapsulated liposomes as a novel therapeutic approach for managing inflammation-driven ocular conditions. The encapsulation of colchicine within liposomes represents a significant innovation, aimed at enhancing biocompatibility and therapeutic efficacy while minimizing cytotoxic effects associated with free colchicine. Our research synthesized colchicine-loaded liposomes and assessed their therapeutic impact on human monocytes, macrophages, and retinal pigment epithelium (RPE) cells in an inflammatory environment. The findings reveal a groundbreaking improvement in treatment strategies, with a substantial reduction in TNF-alpha-induced reactive oxygen species (ROS) and nitric oxide (NO) production in RPE cells. Moreover, the colchicine-loaded liposomes significantly inhibited the proliferation and ROS production in activated monocytes and macrophages and effectively decreased interleukin (IL)-1β and IL-6 secretion, highlighting their strong anti-inflammatory properties and showed slightly better suppression of these two cytokines than dexamethasone-liposomes.},
}
@article {pmid39890008,
year = {2025},
author = {You, L and Zhao, W and Li, X and Yang, C and Guo, P},
title = {Tyrosol protects RPE cells from H2O2-induced oxidative damage in vitro and in vivo through activation of the Nrf2/HO-1 pathway.},
journal = {European journal of pharmacology},
volume = {991},
number = {},
pages = {177316},
doi = {10.1016/j.ejphar.2025.177316},
pmid = {39890008},
issn = {1879-0712},
mesh = {Animals ; *NF-E2-Related Factor 2/metabolism ; *Phenylethyl Alcohol/analogs &amp; derivatives/pharmacology ; *Oxidative Stress/drug effects ; *Hydrogen Peroxide/toxicity ; *Retinal Pigment Epithelium/drug effects/cytology/pathology/metabolism ; Mice ; Cell Line ; Signal Transduction/drug effects ; Humans ; Mice, Inbred C57BL ; *Heme Oxygenase-1/metabolism ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; Male ; Cell Survival/drug effects ; Antioxidants/pharmacology ; },
abstract = {Oxidative stress-induced damage to the retinal pigment epithelium (RPE) is a critical factor in the pathogenesis of age-related macular degeneration (AMD). Tyrosol is a phenolic compound with antioxidant properties, but its protective effect against oxidative stress-induced AMD and its underlying mechanisms are unknown. The aim of this study was to investigate the protective effects of tyrosol on hydrogen peroxide (H2O2)-induced retinal damage and demonstrate its underlying mechanisms in ARPE-19 cells and C57BL/6J mice retinas. We found that tyrosol significantly enhanced the survival of ARPE-19 cells under H2O2-induced oxidative stress in a concentration-dependent manner. It effectively attenuated the production of reactive oxygen species (ROS) and lipid peroxides, while also counteracting the associated reduction in glutathione (GSH) concentration and superoxide dismutase (SOD) activity. Furthermore, pretreatment with tyrosol ameliorated apoptosis-related damage in ARPE-19 cells induced by H2O2 and normalized the levels of apoptosis-related proteins. Notably, tyrosol significantly upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzymes heme oxygenase-1 (HO-1) and NADPH dehydrogenase quinone 1 (NQO1). Interestingly, in vivo study demonstrated that tyrosol administration effectively improved retinal function and morphology in H2O2-exposed mice, restored the thickness of the outer nuclear layer and inner core layer, and normalized the expression of proteins Bax, cleaved caspase-3, and Nrf2, which was consistent with the results of in vitro experiments. Overall, our findings suggest that tyrosol can protect RPE cells from oxidative stress damage by activating the Nrf2/HO-1 pathway, which may be a promising new strategy for the treatment of AMD.},
}
@article {pmid39889868,
year = {2025},
author = {Zhao, Q and Wei, L and Chen, Y},
title = {From bench to bedside: Developing CRISPR/Cas-based therapy for ocular diseases.},
journal = {Pharmacological research},
volume = {213},
number = {},
pages = {107638},
doi = {10.1016/j.phrs.2025.107638},
pmid = {39889868},
issn = {1096-1186},
mesh = {Humans ; Animals ; *Gene Editing/methods ; *CRISPR-Cas Systems ; *Eye Diseases/therapy/genetics ; *Genetic Therapy/methods ; },
abstract = {Vision-threatening disorders, including both hereditary and multifactorial ocular diseases, necessitate innovative therapeutic approaches. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) has emerged as a promising tool for treating ocular diseases through gene editing and expression regulation. This system has contributed to the development of representative disease models, including animal models, organoids, and cell lines, thereby facilitating investigations into the pathogenesis of disease-related genes. Besides, therapeutic applications of CRISPR/Cas have been extensively explored in preclinical in vitro and in vivo studies, targeting various ocular conditions, such as retinitis pigmentosa, Leber congenital amaurosis, Usher syndrome, fundus neovascular diseases, glaucoma, and corneal diseases. Recent advancements have demonstrated the technology's potential to restore cellular homeostasis and alleviate disease phenotypes, thereby prompting a variety of clinical trials. To date, active trials include treatments for primary open angle glaucoma with MYOC mutations, refractory herpetic viral keratitis, CEP290-associated inherited retinal degenerations, neovascular age-related macular degeneration, and retinitis pigmentosa with RHO mutations. However, challenges remain, primarily concerning off-target effects, immunogenicity, ethical considerations, and regulatory particularity. To reach higher safety and efficiency before truly transitioning from bench to bedside, future research should concentrate on improving the specificity and efficacy of Cas proteins, optimizing delivery vectors, and broadening the applicability of therapeutic targets. This review summarizes the application strategies and delivery methods of CRISPR/Cas, discusses recent progress in CRISPR/Cas-based disease models and therapies, and provides an overview of the landscape of clinical trials. Current obstacles and future directions regarding the bench-to-bedside transition are also discussed.},
}
@article {pmid39888884,
year = {2025},
author = {Chen, X and Li, J and Xu, N and Li, X and Li, J and Guo, Q and Zhang, J and Miao, H and Huang, L},
title = {Serum lipids mediate the association of per- and polyfluoroalkyl substances exposure and age-related macular degeneration.},
journal = {PloS one},
volume = {20},
number = {1},
pages = {e0317678},
pmid = {39888884},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/blood/chemically induced/epidemiology ; *Fluorocarbons/blood/adverse effects ; Male ; Female ; Aged ; Alkanesulfonic Acids/blood ; Middle Aged ; *Lipids/blood ; Caprylates/blood ; Nutrition Surveys ; *Environmental Exposure/adverse effects ; Sulfonic Acids/blood ; Risk Factors ; Fatty Acids ; },
abstract = {BACKGROUND: This study aims to investigate the connection between serum lipids, per- and polyfluoroalkyl substances (PFAS), and age-related macular degeneration (AMD) risk and assess whether serum lipids mediate the association between PFAS and AMD.<br><br>METHODS: 1605 participants were enrolled from NHANES 2005-2008. Four serum PFAS levels with high detective rates, including perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) were examined. Restricted cubic spline analysis (RCS) and weighted quantile sum (WQS) analysis were employed to detect nonlinear and mixed exposure effects.<br><br>RESULTS: PFOS level was associated with any AMD (OR, 1.54; 95% CI, 1.12 to 2.11; P = 0.011), early AMD (OR, 1.43; 95% CI, 1.06 to 1.95; P = 0.024), and late AMD (OR, 3.35; 95% CI, 1.55 to 7.23; P = 0.004) risk. PFHxS (OR, 1.72; 95% CI, 1.01 to 2.93; P = 0.045) and PFOA (OR, 2.10; 95% CI, 1.21 to 3.63; P = 0.011) levels were associated with late AMD risk. The RCS showed a nonlinear connection between PFOS exposure and AMD risk (P nonlinear = 0.006). WQS analysis indicated a positive relationship between mixed PFAS exposure and AMD risk (OR, 1.34; 95% CI, 1.03 to 1.75; P = 0.030). Serum total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were associated with AMD risk (ORTC, 1.005; 95% CI, 1.001 to 1.009; P = 0.026. ORHDL, 1.028; 95% CI, 1.014 to 1.042; P<0.001), and mediated the relationship of PFOS exposure and AMD risk, with mediation proportions of 5.73% (P = 0.020) and 7.27% (P = 0.032), respectively.<br><br>CONCLUSIONS: PFOS exposure was connected with AMD risk and serum TC and HDL mediated this relationship.},
}
@article {pmid39888276,
year = {2025},
author = {Fan, X and Jiang, K and Zhao, Y and Lee, BT and Geng, F and Brelen, ME and Lu, W and Wei, G},
title = {Peptide-Bound Aflibercept Eye Drops for Treatment of Neovascular Age-Related Macular Degeneration in Nonhuman Primates.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {11},
pages = {e2410744},
pmid = {39888276},
issn = {2198-3844},
support = {82273864//National Natural Science Fund of China/ ; 21ZR1407100//Shanghai Science and Technology Program/ ; 21S11905300//Shanghai Science and Technology Program/ ; 20180101//Development Project of Shanghai Peak Disciplines-Integrative Medicine/ ; },
mesh = {Animals ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/pharmacology/therapeutic use ; Macaca fascicularis ; *Ophthalmic Solutions ; *Macular Degeneration/drug therapy ; Disease Models, Animal ; *Choroidal Neovascularization/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors ; Intravitreal Injections ; *Peptides ; Humans ; },
abstract = {The advent of biomacromolecules antagonizing vascular endothelial growth factor (VEGF) has revolutionized the treatment of neovascular age-related macular degeneration (nAMD). However, frequent intravitreal injections of these biomacromolecules impose an enormous burden on patients and create a massive workload for healthcare providers. This causes patients to abandon therapy, ultimately leading to progressive and irreversible vision loss. In order to address this unmet clinical need, a noninvasive treatment for nAMD is developed. An optimized cell-penetrating peptide derivative, [bxy]Penetratin (bxyWP), is used to non-covalently complex with the anti-VEGF protein aflibercept (AFL) via reversible hydrophobic interaction. The interaction is crucial for AFL delivery, neither impairing the affinity of AFL to pathological VEGF, nor being interfered by endogenous proteins in tear fluids. AFL/bxyWP eye drops exhibit prolonged retention on the eye and excellent absorption into the posterior ocular segment following topical administration, with significant drug distribution to the retina and choroid. In a laser-induced choroidal neovascularization model on cynomolgus monkeys, AFL/bxyWP eye drops efficiently reduce lesion size and leakage comparable to conventional intravitreal injection of AFL. These results suggest that AFL/bxyWP eye drops are feasible self-administered treatment for neovascular retinal diseases and potentially become a substitute for intravitreal injections.},
}
@article {pmid39886454,
year = {2024},
author = {Rossi, S and Gesualdo, C and Marano, E and Perrotta, R and Trotta, MC and Del Giudice, A and Simonelli, F},
title = {Treatment of neovascular age-related macular degeneration: one year real-life results with intravitreal Brolucizumab.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1467160},
pmid = {39886454},
issn = {2296-858X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a prevalent cause of irreversible vision loss worldwide, particularly among the elderly population. Two forms of late AMD are described: neovascular AMD (nAMD), characterized by abnormal choroidal blood vessel growth, and atrophic (dry) AMD, involving retinal cell degeneration. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have transformed nAMD treatment, with Brolucizumab emerging as a promising therapy. The aim of this study is to provide the real-life anatomical-functional and safety results, after 1 year of treatment experience with Brolucizumab.<br><br>METHODS: This is a retrospective observational real-life study in which 44 patients (44 eyes) diagnosed with nAMD and treated with Brolucizumab were enrolled. We identified two groups: group 1 (24 treatment-na&#xef;ve eyes) that received a loading dose of 3 monthly intravitreal injections of Broluciziumab 6&#x202f;mg (0.05&#x202f;mL solution)&#x202f;+&#x202f;Q8w/Q12w regimen, and a Group 2 (20 non-na&#xef;ve eyes) which performed 1 injection + ProReNata (PRN) scheme. Monthly, all participants underwent comprehensive ophthalmological evaluation until 12&#x202f;months follow-up.<br><br>RESULTS: We observed a significant improvement in best corrected visual acuity (39&#x202f;&#xb1;&#x202f;15&#x202f;L vs. 30&#x202f;&#xb1;&#x202f;17&#x202f;L; p&#x202f;<&#x202f;0.01) and central retinal thickness (265&#x202f;&#xb1;&#x202f;89&#x202f;&#x3bc; vs. 360&#x202f;&#xb1;&#x202f;129&#x202f;&#x3bc;; p&#x202f;<&#x202f;0.0001) at the end of follow-up without any differences between treatment-na&#xef;ve and non-na&#xef;ve patients. These results were obtained with a low number of injections (3.7&#x202f;&#xb1;&#x202f;1.9) with only one case of intraocular drug-related adverse event. Finally, the presence of subretinal hyperreflective material correlates with lower visual recovery.<br><br>DISCUSSION: Our findings highlight the efficacy of Brolucizumab in managing wet-AMD and suggest its role for long-term efficacy in stabilizing retinal exudation and fluid accumulation, resulting in improved visual prognosis.},
}
@article {pmid39884544,
year = {2025},
author = {Mishra, M and Cashman, SM and Kumar-Singh, R},
title = {Intravitreal AAV-IKV mediated delivery of decorin inhibits choroidal neovascularization, fibrosis, inflammation and elevates autophagy.},
journal = {Experimental eye research},
volume = {252},
number = {},
pages = {110258},
doi = {10.1016/j.exer.2025.110258},
pmid = {39884544},
issn = {1096-0007},
mesh = {Animals ; *Decorin/genetics/administration &amp; dosage ; Intravitreal Injections ; *Choroidal Neovascularization/prevention &amp; control/metabolism/pathology ; Fibrosis/prevention &amp; control ; Mice ; *Autophagy ; *Dependovirus/genetics ; Disease Models, Animal ; Mice, Inbred C57BL ; Inflammation/prevention &amp; control ; Humans ; *Genetic Therapy/methods ; Genetic Vectors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors ; },
abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. The exudative or wet form of AMD is caused by choroidal neovascularization (CNV) and subsequently a macular edema. Wet AMD can be effectively treated with anti-vascular endothelial growth factor (VEGF) therapies. However, despite treatment, more than half of patients continue to lose vision due to a lack of compliance with frequent intravitreal injections, failure to adequately respond to anti-VEGF therapy and emergence of fibrotic scars underneath the retina. In this study we investigated the use of our retinal penetrating AAV for delivery of human decorin (AAV-IKV-Decorin) in a murine model of laser induced CNV. Our results indicate that following a single intravitreal injection, decorin is highly expressed in the outer retina of AAV-IKV-Decorin injected mice and such mice exhibit significantly less neovascularization in laser induced CNV relative to mice injected with an AAV-IKV-Aflibercept, an AAV expressing an anti-VEGF. AAV-IKV-Decorin also significantly inhibited fibrosis, reduced inflammatory markers and increased autophagy.},
}
@article {pmid39884366,
year = {2025},
author = {Hwang, G and Lee, SH and Lee, DY and Park, C and Roh, HW and Son, SJ and Park, RW},
title = {Age-related eye diseases and subsequent risk of mental disorders in older adults: A real-world multicenter study.},
journal = {Journal of affective disorders},
volume = {375},
number = {},
pages = {306-315},
doi = {10.1016/j.jad.2025.01.128},
pmid = {39884366},
issn = {1573-2517},
mesh = {Humans ; Aged ; Male ; Female ; Republic of Korea/epidemiology ; *Eye Diseases/epidemiology/psychology ; Middle Aged ; *Mental Disorders/epidemiology/etiology ; Aged, 80 and over ; Risk Factors ; Dementia/epidemiology ; *Macular Degeneration/epidemiology ; *Depressive Disorder/epidemiology ; Longitudinal Studies ; Cataract/epidemiology ; Glaucoma/epidemiology ; Proportional Hazards Models ; Anxiety Disorders/epidemiology ; },
abstract = {BACKGROUND: The relationship between age-related eye diseases and the subsequent risk of dementia and depressive disorders remains inconsistent. Furthermore, the effects on anxiety disorders and sleep disorders have been underexplored. This study aims to comprehensively examine the impact of age-related eye diseases on common mental disorders in older adults, thereby enhancing our understanding of the mental health implications in these conditions.<br><br>METHODS: The electronic health records of 1,522,036 patients aged over 60 from ten institutions in South Korea were analyzed. Patients with and without age-related eye diseases were identified, and 1:4 propensity score matching (PSM) was implemented. A 10-year longitudinal analysis was conducted using the Cox proportional hazards model to calculate the hazard ratios (HR). A meta-analysis was performed to combine the results from different institutions. Subgroup analyses were conducted to explore the impact of specific age-related eye diseases (cataract, glaucoma, age-related macular degeneration) on mental disorders.<br><br>RESULTS: A total of 41,637 patients with age-related eye disease were matched with 134,908 patients without such conditions. Patients with age-related eye disease showed a significantly higher risk of mental disorders (dementia, HR: 1.21 [95&#xa0;% CI: 1.14-1.27]; depressive disorders, HR: 1.28 [95&#xa0;% CI: 1.20-1.36]; anxiety disorders, HR: 1.31 [95&#xa0;% CI: 1.22-1.41]; sleep disorders, HR: 1.29 [95&#xa0;% CI: 1.22-1.37]). In subgroup analyses, each of the three age-related eye diseases was significantly associated with an increased risk of mental disorders. (cataract, HR: 1.25-1.33; glaucoma, HR: 1.15-1.49; age-related macular degeneration, HR: 1.18-1.37).<br><br>CONCLUSION: Age-related eye diseases increase the risk of developing mental disorders in older adults, highlighting the need for a multidisciplinary approach to patient care in these conditions.},
}
@article {pmid39883882,
year = {2025},
author = {Huang, Y and Zhang, X and Liang, L and Jiang, Y and Li, B and Zhu, X and Li, C and Gu, C and Zou, W and Zheng, Z and Zhao, S},
title = {Longer recreational screen time contributes to the risk of age-related macular degeneration: a UK Biobank cohort study and two-sample Mendelian randomisation.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04029},
pmid = {39883882},
issn = {2047-2986},
mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; United Kingdom/epidemiology ; Female ; Mendelian Randomization Analysis ; Aged ; Middle Aged ; Prospective Studies ; Biological Specimen Banks ; *Screen Time ; Risk Factors ; Cross-Sectional Studies ; Tomography, Optical Coherence ; Genome-Wide Association Study ; Proportional Hazards Models ; UK Biobank ; },
abstract = {BACKGROUND: Recreational screen time (RST) has been found to be associated with cognitive decline and neurodegenerative diseases. However, the association between RST and age-related macular degeneration (AMD), an ocular neurodegenerative disease, is still unclear. We aimed to elucidate the association between RST and AMD.<br><br>METHODS: This study consisted of three parts: 1) a prospective cohort study with 482&#x2009;939 UK Biobank participants and a 12.8-year median follow-up to explore the association between RST and incident AMD; 2) a two-sample Mendelian randomisation (MR) analysis using summary-level genome-wide association analysis data for RST based on 526&#x2009;725 European individuals to assess causality between RST and AMD; and 3) a cross-sectional study involving 38&#x2009;478 UK Biobank individuals with optical coherence tomography data to investigate the link between RST and retinal thickness.<br><br>RESULTS: Multivariable Cox proportional-hazards models showed that an increase in total daily RST was associated with a greater risk of developing AMD (hazard ratio (HR) per standard deviation (SD) increase&#x2009;=&#x2009;1.05; 95% confidence interval (CI)&#x2009;=&#x2009;1.03, 1.07, P&#x2009;<&#x2009;0.001). With further analysis, we revealed that daily high RST (>4 h/d) significantly increased the risk of AMD compared with low RST (0-3 h/d) (HR&#x2009;=&#x2009;1.09; 95% CI&#x2009;=&#x2009;1.04, 1.15, P&#x2009;=&#x2009;0.001), while moderate RST (3.5-4 h/d) had no significant effect on AMD. Restricted cubic spline plots revealed a linear dose-response association between RST and AMD. With MR analysis we confirmed the potential causal association between RST and AMD (odds ratio per SD&#x2009;=&#x2009;1.26; 95% CI&#x2009;=&#x2009;1.01, 1.59, P&#x2009;=&#x2009;0.042). Multivariable linear models suggested that an increase in RST was associated with thinning of the outer and inner retinal layers and total macular thickness.<br><br>CONCLUSIONS: Longer RST may be a potential causal risk factor for AMD and may lead to pathological retinal thinning. Reducing RST could be beneficial for preventing AMD, and future research should identify the most effective time points for intervening on RST.},
}
@article {pmid39881194,
year = {2025},
author = {Veritti, D and Sarao, V and Lanzetta, P},
title = {From pro-re-nata to fixed-interval regimen: evolving real-world treatment paradigms in anti-VEGF therapy for neovascular AMD.},
journal = {Eye (London, England)},
volume = {39},
number = {7},
pages = {1349-1355},
pmid = {39881194},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; *Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Female ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Ranibizumab/administration &amp; dosage ; *Bevacizumab/administration &amp; dosage ; Aged, 80 and over ; Tomography, Optical Coherence ; Treatment Outcome ; Middle Aged ; Follow-Up Studies ; Drug Administration Schedule ; Recombinant Fusion Proteins/administration &amp; dosage ; },
abstract = {OBJECTIVE: To evaluate the impact of evolving treatment paradigms for neovascular age-related macular degeneration (nAMD) by comparing outcomes between two patient cohorts treated with different anti-vascular endothelial growth factor (anti-VEGF) regimens over a decade apart.<br><br>METHODS: This retrospective cohort study included 200 treatment-naive nAMD patients divided into two cohorts. Cohort 1 (2009-2010) was treated with a pro re nata (PRN) regimen, involving three initial monthly injections followed by as-needed treatments based on monthly monitoring. Cohort 2 (2019-2021) received a fixed-interval regimen, consisting of three initial monthly injections followed by bimonthly maintenance doses. Primary outcomes included changes in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 12 months. Secondary outcomes included the number of injections, follow-up visits, and adherence to treatment schedules.<br><br>RESULTS: Cohort 2 demonstrated significantly greater improvement in BCVA (+5.5 vs -2.0 ETDRS letters, p&#x2009;<&#x2009;0.001) and CRT reduction (-101.7 vs -26.5&#x2009;&#x3bc;m, p&#x2009;<&#x2009;0.001) compared to Cohort 1. Patients in Cohort 2 received more injections (7.7 vs 4.8, p&#x2009;<&#x2009;0.001) but required fewer monitoring visits (3.2 vs 5.1, p&#x2009;<&#x2009;0.001). Adherence to treatment schedules was markedly higher in Cohort 2 (78% vs 0%, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: The transition from a PRN to a fixed-interval anti-VEGF regimen significantly improved visual and anatomical outcomes in nAMD patients. Fixed-interval regimens not only enhanced treatment efficacy but also optimized resource utilization, suggesting a superior approach for managing nAMD in a real-world clinical setting.},
}
@article {pmid39880333,
year = {2025},
author = {Izrael, M and Chebath, J and Molakandov, K and Revel, M},
title = {Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.},
journal = {Advanced drug delivery reviews},
volume = {218},
number = {},
pages = {115525},
doi = {10.1016/j.addr.2025.115525},
pmid = {39880333},
issn = {1872-8294},
mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Pluripotent Stem Cells/transplantation/cytology ; Animals ; *Cell- and Tissue-Based Therapy/methods ; *Stem Cell Transplantation/methods ; Clinical Trials as Topic ; },
abstract = {Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems. Over the past two decades, comprehensive preclinical efficacy (proof-of-concept) and safety studies have led to the initiation of First-in-Human phase I-II clinical trials for a range of neurodegenerative diseases. In this review, we explore the fundamentals and challenges of neural-cell therapies derived from pluripotent stem cells for treating neurodegenerative diseases. Additionally, we highlight key preclinical investigations that paved the way for regulatory approvals of these trials. Furthermore, we provide an overview on progress and status of clinical trials done so far in treating neurodegenerative diseases such as spinal cord injury (SCI), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), as well as advances in retina diseases such as Stargardt disease (a.k.a fundus flavimaculatus), retinitis pigmentosa (RP) and age-related macular degeneration (AMD). These trials will pave the way for the development of new cell-based therapies targeting additional neurological conditions, including Alzheimer's disease and epilepsy.},
}
@article {pmid39880118,
year = {2025},
author = {Tang, J and Zhou, C and Ye, F and Zuo, S and Zhou, M and Lu, L and Chai, P and Fan, X},
title = {RNA methylation homeostasis in ocular diseases: All eyes on Me.},
journal = {Progress in retinal and eye research},
volume = {105},
number = {},
pages = {101335},
doi = {10.1016/j.preteyeres.2025.101335},
pmid = {39880118},
issn = {1873-1635},
mesh = {Humans ; *Eye Diseases/genetics/metabolism ; Methylation ; *RNA/metabolism/genetics ; *Homeostasis/physiology ; Animals ; *Epigenesis, Genetic ; RNA Methylation ; },
abstract = {RNA methylation is a pivotal epigenetic modification that adjusts various aspects of RNA biology, including nuclear transport, stability, and the efficiency of translation for specific RNA candidates. The methylation of RNA involves the addition of methyl groups to specific bases and can occur at different sites, resulting in distinct forms, such as N6-methyladenosine (m[6]A), N1-methyladenosine (m[1]A), 5-methylcytosine (m[5]C), and 7-methylguanosine (m[7]G). Maintaining an optimal equilibrium of RNA methylation is crucial for fundamental cellular activities such as cell survival, proliferation, and migration. The balance of RNA methylation is linked to various pathophysiological conditions, including senescence, cancer development, stress responses, and blood vessel formation, all of which are pivotal for comprehending a spectrum of eye diseases. Recent findings have highlighted the significant role of diverse RNA methylation patterns in ophthalmological conditions such as age-related macular degeneration, diabetic retinopathy, cataracts, glaucoma, uveitis, retinoblastoma, uveal melanoma, thyroid eye disease, and myopia, which are critical for vision health. This thorough review endeavors to dissect the influence of RNA methylation on common and vision-impairing ocular disorders. It explores the nuanced roles that RNA methylation plays in key pathophysiological mechanisms, such as oxidative stress and angiogenesis, which are integral to the onset and progression of these diseases. By synthesizing the latest research, this review offers valuable insights into how RNA methylation could be harnessed for therapeutic interventions in the field of ophthalmology.},
}
@article {pmid39880106,
year = {2025},
author = {Csincsik, L and Cheung, CMG and Bannon, F and Peto, T and Chakravarthy, U},
title = {Agreement Between Color, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography in the Detection of Macular Fibrosis in Neovascular Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {272},
number = {},
pages = {126-135},
doi = {10.1016/j.ajo.2025.01.011},
pmid = {39880106},
issn = {1879-1891},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Wet Macular Degeneration/diagnosis/drug therapy ; Female ; Male ; Aged ; Visual Acuity/physiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fibrosis/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; *Macula Lutea/pathology ; Reproducibility of Results ; Middle Aged ; Multimodal Imaging ; Choroidal Neovascularization/diagnosis/drug therapy ; },
abstract = {PURPOSE: To evaluate the agreement between fibrosis on color imaging-, fluorescein angiography (FA)-, and spectral domain optical coherence tomography (SD-OCT)-detected hyperreflective material (HRM) and assess their clinical relevance.<br><br>DESIGN: Clinical cohort and diagnostic accuracy study.<br><br>METHODS: Multimodal fundus images (color, FA, and SD-OCT) of 130 eyes with neovascular age-related macular degeneration, collected 18 months after the initiation of anti-vascular endothelial growth factor treatment (anti-VEGF) as part of the Early Detection of Neovascular AMD (EDNA) study, were regraded for fibrosis and HRM. HRM location was assigned as subretinal (SR) and/or subretinal pigment epithelial (SPE). Agreement between detection methods was assessed with the kappa statistic, and regression analysis with best corrected visual acuity (BCVA) as outcome variable was used to evaluate clinical relevance.<br><br>RESULTS: Kappa was 0.56 for FA and 0.40 for HRM on SD-OCT, using color as the reference. Regression against BCVA showed low R&#xb2; values for all tests (R&#xb2; < 0.09). In the HRM-OCT model, with no HRM as the reference and location and dimensions as covariates, the R&#xb2; increased to 0.301. Letter loss was 21.1 (P < .0001) for SR and 8.1 (P = .045) for SPE. When HRM on SD-OCT was the reference, the sensitivity for color and FA combination was 87.5% but was lower at 33.3% for SPE only.<br><br>CONCLUSIONS: Well-defined HRM detected by SD-OCT during the maintenance phase of anti-VEGF therapy explains BCVA variance, positioning OCT as a superior standard for detecting fibrosis.},
}
@article {pmid39878697,
year = {2025},
author = {Rubinstein, JF and Alcalde, NG and Chopin, A and Verghese, P},
title = {Oculomotor challenges in macular degeneration impact motion extrapolation.},
journal = {Journal of vision},
volume = {25},
number = {1},
pages = {17},
pmid = {39878697},
issn = {1534-7362},
support = {R01 EY027390/EY/NEI NIH HHS/United States ; T32 EY025201/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Motion Perception/physiology ; Male ; *Scotoma/physiopathology ; Female ; *Macular Degeneration/physiopathology ; Fixation, Ocular/physiology ; Aged ; Middle Aged ; *Eye Movements/physiology ; Visual Fields/physiology ; Visual Acuity/physiology ; Photic Stimulation/methods ; },
abstract = {Macular degeneration (MD), which affects the central visual field including the fovea, has a profound impact on acuity and oculomotor control. We used a motion extrapolation task to investigate the contribution of various factors that potentially impact motion estimation, including the transient disappearance of the target into the scotoma, increased position uncertainty associated with eccentric target positions, and increased oculomotor noise due to the use of a non-foveal locus for fixation and for eye movements. Observers performed a perceptual baseball task where they judged whether the target would intersect or miss a rectangular region (the plate). The target was extinguished before reaching the plate and participants were instructed either to fixate a marker or smoothly track the target before making the judgment. We tested nine eyes of six participants with MD and four control observers with simulated scotomata that matched those of individual participants with MD. Both groups used their habitual oculomotor locus-eccentric preferred retinal locus (PRL) for MD and fovea for controls. In the fixation condition, motion extrapolation was less accurate for controls with simulated scotomata than without, indicating that occlusion by the scotoma impacted the task. In both the fixation and pursuit conditions, MD participants with eccentric preferred retinal loci typically had worse motion extrapolation than controls with a matched artificial scotoma and foveal preferred retinal loci. Statistical analysis revealed occlusion and target eccentricity significantly impacted motion extrapolation in the pursuit condition, indicating that these factors make it challenging to estimate and track the path of a moving target in MD.},
}
@article {pmid39877463,
year = {2025},
author = {Veturi, YA and McNamara, S and Kinder, S and Clark, CW and Thakuria, U and Bearce, B and Manoharan, N and Mandava, N and Kahook, MY and Singh, P and Kalpathy-Cramer, J},
title = {EyeLiner: A Deep Learning Pipeline for Longitudinal Image Registration Using Fundus Landmarks.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100664},
pmid = {39877463},
issn = {2666-9145},
abstract = {OBJECTIVE: Detecting and measuring changes in longitudinal fundus imaging is key to monitoring disease progression in chronic ophthalmic diseases, such as glaucoma and macular degeneration. Clinicians assess changes in disease status by either independently reviewing or manually juxtaposing longitudinally acquired color fundus photos (CFPs). Distinguishing variations in image acquisition due to camera orientation, zoom, and exposure from true disease-related changes can be challenging. This makes manual image evaluation variable and subjective, potentially impacting clinical decision-making. We introduce our deep learning (DL) pipeline, "EyeLiner," for registering, or aligning, 2-dimensional CFPs. Improved alignment of longitudinal image pairs may compensate for differences that are due to camera orientation while preserving pathological changes.<br><br>DESIGN: EyeLiner registers a "moving" image to a "fixed" image using a DL-based keypoint matching algorithm.<br><br>PARTICIPANTS: We evaluate EyeLiner on 3 longitudinal data sets: Fundus Image REgistration (FIRE), sequential images for glaucoma forecast (SIGF), and our internal glaucoma data set from the Colorado Ophthalmology Research Information System (CORIS).<br><br>METHODS: Anatomical keypoints along the retinal blood vessels were detected from the moving and fixed images using a convolutional neural network and subsequently matched using a transformer-based algorithm. Finally, transformation parameters were learned using the corresponding keypoints.<br><br>MAIN OUTCOME MEASURES: We computed the mean distance (MD) between manually annotated keypoints from the fixed and the registered moving image. For comparison to existing state-of-the-art retinal registration approaches, we used the mean area under the curve (AUC) metric introduced in the FIRE data set study.<br><br>RESULTS: EyeLiner effectively aligns longitudinal image pairs from FIRE, SIGF, and CORIS, as qualitatively evaluated through registration checkerboards and flicker animations. Quantitative results show that the MD decreased for this model after alignment from 321.32 to 3.74 pixels for FIRE, 9.86 to 2.03 pixels for CORIS, and 25.23 to 5.94 pixels for SIGF. We also obtained an AUC of 0.85, 0.94, and 0.84 on FIRE, CORIS, and SIGF,&#xa0;respectively, beating the current state-of-the-art SuperRetina (AUCFIRE&#xa0;= 0.76, AUCCORIS&#xa0;= 0.83, AUCSIGF&#xa0;=&#xa0;0.74).<br><br>CONCLUSIONS: Our pipeline demonstrates improved alignment of image pairs in comparison to the current state-of-the-art methods on 3 separate data sets. We envision that this method will enable clinicians to align image pairs and better visualize changes in disease over time.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39876708,
year = {2025},
author = {Siqueira, RC},
title = {Optimal Timing of Photobiomodulation Therapy for Retinal Diseases: Leveraging Circadian Mitochondrial Rhythms.},
journal = {Photobiomodulation, photomedicine, and laser surgery},
volume = {43},
number = {3},
pages = {81-82},
doi = {10.1089/photob.2024.0154},
pmid = {39876708},
issn = {2578-5478},
mesh = {Humans ; *Low-Level Light Therapy/methods ; *Mitochondria/radiation effects/physiology ; *Circadian Rhythm/physiology ; *Retinal Diseases/radiotherapy ; },
abstract = {Age-related retinal degeneration is associated with mitochondrial dysfunction. Emerging evidence suggests that photobiomodulation therapy (PBMT) using near-infrared light may improve mitochondrial function and visual performance, but its efficacy is critically time-dependent. This article explores how daily biological rhythms and mitochondrial function interact, focusing on the potential of timed PMBT for age-related eye diseases. Further research is needed to determine optimal treatment times and individual responses to maximize this therapy's benefits.},
}
@article {pmid39875939,
year = {2025},
author = {Zhang, PW and Wan, ZH and Li, W and Vats, A and Mehta, K and Fan, L and Zhou, L and Li, S and Li, G and Keuthan, CJ and Berlinicke, C and Qian, C and Esumi, N and Duh, EJ and Zack, DJ},
title = {Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration.},
journal = {Journal of neuroinflammation},
volume = {22},
number = {1},
pages = {20},
pmid = {39875939},
issn = {1742-2094},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; P30 EY001765/NH/NIH HHS/United States ; },
mesh = {Animals ; *Retinal Degeneration/etiology/prevention &amp; control/pathology/drug therapy ; Mice ; *Necroptosis/drug effects/physiology ; *Ibuprofen/pharmacology/therapeutic use ; *Anti-Inflammatory Agents, Non-Steroidal/pharmacology/therapeutic use ; Mice, Inbred C57BL ; *Inflammation/drug therapy/etiology/pathology ; *Light/adverse effects ; Male ; *Photoreceptor Cells, Vertebrate/drug effects/pathology ; Electroretinography ; },
abstract = {BACKGROUND: The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation. To further explore this relationship, we tested whether Ibuprofen (IBU), an FDA-approved non-steroidal anti-inflammatory drug (NSAID), could promote PR survival and function in a mouse model of light damage (LD)-induced PR degeneration.<br><br>METHODS: LD was induced by exposing mice to 4000&#xa0;lx of light for 2-4&#xa0;hours (h). IBU (100 or 200&#xa0;mg/kg) or vehicle was administered by daily intraperitoneal injection. Retinal structure and function were evaluated by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG). Cell death genes were analyzed at 24 and 72&#xa0;h after LD using the Mouse Pan-Cell Death Pathway PCR Array (88 genes). The cellular location and protein expression of key necroptosis genes were assessed by immunohistochemistry.<br><br>RESULTS: Retinal outer nuclear layer (ONL) thickness in vehicle-injected LD animals was 8.7&#x2009;&#xb1;&#x2009;0.6% of retinas without LD (p&#x2009;<&#x2009;0.0001). In IBU 200&#xa0;mg/kg treated mice, central ONL thickness was 74.9&#x2009;&#xb1;&#x2009;7.7% of untreated retinas (p&#x2009;<&#x2009;0.001). A-wave and b-wave ERG amplitudes were significantly preserved in IBU-treated animals. IBU significantly inhibited retinal inflammation. Twenty-four hour after LD, retinal mRNA expression for the inflammatory-factors tumor necrosis factor (Tnf), interleukin-1 beta (Il1B), and C-C motif chemokine ligand 2 (Ccl2) increased by 10-, 17-, and 533-fold, respectively; in IBU-treated animals, the expression levels of these inflammatory factors were not significantly different from no-LD controls. Expression of key necroptosis genes, including Ripk3 and Mlkl, were upregulated in LD vehicle-treated mice, but dramatically reduced to near no LD levels in LD IBU-treated mice. Microglia activation and MLKL protein upregulation were observed primarily in photoreceptors 12&#xa0;h after LD, as assessed by immunohistochemistry. IBU reduced the upregulation of MLKL protein and microglia migration in the ONL and outer plexiform layer (OPL) of treated retinas.<br><br>CONCLUSIONS: Systemic administration of the anti-inflammatory drug IBU partially protected mouse retinas from light-induced photochemical damage and inhibited both inflammation and the necroptosis cell death pathways. Our results suggest that NSAIDs may provide a promising therapeutic approach for treatment of the human retinal degenerative diseases.},
}
@article {pmid39875573,
year = {2025},
author = {Ueda-Consolvo, T and Takahashi, S and Oiwake, T and Nakamura, T and Ishida, M and Yanagisawa, S and Hayashi, A},
title = {Assessment of retinal pigment epithelium tears in eyes with submacular hemorrhage secondary to age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {3606},
pmid = {39875573},
issn = {2045-2322},
mesh = {Humans ; Female ; Male ; Aged ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Retinal Hemorrhage/etiology/surgery/pathology ; Tomography, Optical Coherence ; Retrospective Studies ; *Macular Degeneration/complications ; *Retinal Perforations/etiology/surgery/pathology ; Visual Acuity ; Aged, 80 and over ; Vitrectomy ; Middle Aged ; Tissue Plasminogen Activator ; },
abstract = {To assess retinal pigment epithelium (RPE) tears in eyes which underwent pars plana vitrectomy (PPV) for submacular hemorrhage (SMH) secondary to age-related macular degeneration and to investigate the prognostic factors of visual outcomes. This study was a retrospective, observational case series that included 24 eyes of 24 patients who underwent PPV with subretinal tissue plasminogen activator and air for SMH. RPE tears were investigated using spectral-domain or swept-source optical coherence tomography images with raster scan, combined confocal scanning laser ophthalmoscope near-infrared images and color fundus photographs. Multiple regression analysis was performed to identify the predictors of visual outcome at month 3 and 6 after surgery. In 21 eyes out of 24 eyes (87.5%), RPE tear was detected in the posterior pole. Eight eyes (33.3%) had large RPE tears (≧ 1 disc diameter (DD)). Out of the 8 eyes, 5 eyes progressed fibrotic scars within 3 months despite successful SMH removal and showed decrease in their visual acuity (VA). The ratio of eyes with large RPE tears (≧ 1DD) were significantly higher in eyes which had undergone anti-VEGF therapy within 3 months than in treatment-naïve eyes (71.4% vs. 25.0%, p = 0.048). The multiple regression analysis revealed that a small RPE tear (< 1DD) and treatment-naïve condition were associated with better VA at month 3 and 6. SMH within 3 months after anti-VEGF therapy might be accompanied by a large RPE tear. An RPE tear which was smaller than 1DD and treatment-naïve condition were associated with better prognosis.},
}
@article {pmid39875085,
year = {2025},
author = {Chen, M and Shu, Q and Li, F and Li, L and Fan, X},
title = {The whole life cycle myopia management.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {14},
number = {6},
pages = {100161},
doi = {10.1016/j.apjo.2025.100161},
pmid = {39875085},
issn = {2162-0989},
mesh = {Humans ; *Myopia/therapy/physiopathology/epidemiology ; Disease Progression ; *Disease Management ; *Refraction, Ocular/physiology ; *Quality of Life ; Risk Factors ; Child ; },
abstract = {Myopia stands as a prevalent ocular condition with global implications, impacting individuals at various life stages. In school-age children and adolescents, uncorrected myopia impedes reading and academic performance. Among middle-aged and elderly populations, myopia poses severe risks such as macular degeneration, macular holes and retinal detachment, leading to irreversible visual impairment. The term "myopia management" is widely embraced by ophthalmic practitioners and optometry associations worldwide, encompassing strategies to correct refractive errors and ongoing assessment of disease progression, aiming to reduce the progression of myopia and axial elongation. To date, current management strategies for myopia include public health policies, optical solutions, medical interventions and surgical options, but these interventions are general and lack age specificity. Despite existing interventions, we propose the concept of "Whole Life Cycle Myopia Management" in this review. This approach outlined major risk factors of myopia through the whole life cycle, discussed current interventions for myopia and provided age-specific management strategies for myopia of eight different life stages-infancies, toddlers, preschoolers, school-age children, adolescents, young adults, middle-age and old-age, including the prevention of myopia onset, slowing of myopia progression and monitoring of myopia complications. Achieving the "Whole Life Cycle Myopia Management" requires collaborations efforts from government, schools, hospitals and families, to restore vision and enhance the quality of life for those individuals affected by myopia.},
}
@article {pmid39873650,
year = {2025},
author = {Xu, W and Cao, L and Liu, H},
title = {CAMK2D and Complement Factor I-Involved Calcium/Calmodulin Signaling Modulates Sodium Iodate-Induced Mouse Retinal Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {1},
pages = {63},
pmid = {39873650},
issn = {1552-5783},
mesh = {Animals ; Mice ; Iodates/toxicity ; *Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Disease Models, Animal ; Apoptosis ; *Retinal Degeneration/metabolism/chemically induced/genetics ; Electroretinography ; Mice, Inbred C57BL ; Tomography, Optical Coherence ; Blotting, Western ; Flow Cytometry ; Humans ; *Calcium Signaling/physiology ; Cell Line ; Male ; },
abstract = {PURPOSE: To investigate the effect of Ca2+/calmodulin-dependent protein kinase II (CAMKII) δ subtypes (CAMK2D) on sodium iodate (NaIO3)-induced retinal degeneration in mice.<br><br>METHODS: Bioinformatics analysis and Western blot experiments were used to screen the significantly differentially expressed genes in age-related macular degeneration (AMD) disease. CAMK2D knockdown and overexpression models were constructed by lentivirus (LV) infection of adult retinal pigment epithelial cell line-19 (ARPE-19) cells in vitro. Flow cytometry was used to detect ARPE-19 cell apoptosis induced by NaIO3. In vivo, CAMK2D knockdown and overexpression mouse models were generated by infecting mouse retinal pigment epithelium (RPE) with adeno-associated virus (AAV). Retinography, optical coherence tomography (OCT), and histological analysis (hematoxylin and eosin staining) were used to detect NaIO3-induced retinal structural changes in mice. Electroretinography (ERG) was used to detect NaIO3-induced retinal function changes in mice. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the apoptosis of retinal cells induced by NaIO3. RNA sequencing (RNA-Seq) and bioinformatics analysis were used to screen for target genes affected by CAMK2D in CAMK2D-overexpressing ARPE-19 cells. And flow cytometry, OCT, and ERG were used to evaluate the regulatory effect of CAMK2D on target genes.<br><br>RESULTS: Bioinformatics analysis found the expression of genes related to Ca2+ signal was significantly reduced in AMD patients. Western blot showed that in a mouse model of dry AMD induced by NaIO3, CAMK2D expression in RPE-Choroid tissue significantly lower than normal mice. In vitro, our results showed that overexpression of CAMK2D in ARPE-19 cells decreased apoptosis induced by NaIO3 and knockdown increased apoptosis. In vivo, CAMK2D overexpression in RPE cells can attenuate the retina degeneration induced by NaIO3 and CAMK2D knockdown aggravated degeneration. The bioinformatics analysis indicated that CAMK2D might affect AMD pathology through complement factor I (CFI). In vitro, knockdown of CFI in ARPE-19 cells increased apoptosis induced by NaIO3. In knockdown CFI ARPE-19 cells, overexpression of CAMK2D reduced the above apoptosis. In mice retina, CFI knockdown can aggravate the retina degeneration induced by NaIO3. In knockdown CFI mice, overexpression of CAMK2D in RPE can attenuate the above retina degeneration. Western blot confirmed that CAMK2D regulated the expression of CFI in mice.<br><br>CONCLUSIONS: CAMK2D can attenuate the retinal degeneration induced by NaIO3, which was achieved by regulating the CFI.},
}
@article {pmid39870835,
year = {2025},
author = {Bindewald-Wittich, A and Alkabouni, MW and Wolf, A},
title = {[Optical coherence tomography biomarkers for neovascular age-related macular degeneration : Relevance for the diagnosis, treatment and prognosis].},
journal = {Die Ophthalmologie},
volume = {122},
number = {2},
pages = {144-156},
pmid = {39870835},
issn = {2731-7218},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Prognosis ; Biomarkers/analysis ; *Wet Macular Degeneration/diagnosis/therapy/pathology ; *Macular Degeneration/diagnosis/therapy/pathology ; },
abstract = {Comprehensive multimodal imaging is essential for the precise clinical diagnostics of neovascular age-related macular degeneration (nAMD). Noninvasive optical coherence tomography (OCT) is of prime importance regarding the baseline examination, follow-up and monitoring during treatment. The OCT imaging in nAMD eyes enables a high-resolution assessment of the retinal micromorphology, which can be considerably disturbed in different layers. A large number of pathological OCT alterations represent distinct micromorphological OCT biomarkers. These should be taken into account in the assessment of OCT images. This article covers the following important biomarkers: intraretinal, subretinal and subpigment epithelial fluid, outer retinal tubulations, ellipsoid zone integrity, hyperreflective foci, subretinal drusenoid deposits, onion sign, hyporeflective prechoroidal cleft, double layer sign, subretinal hyperreflective material and bacillary layer detachment.},
}
@article {pmid39870644,
year = {2025},
author = {Chen, Y and Jiang, M and Li, L and Yang, S and Liu, Z and Lin, S and Wang, W and Li, J and Chen, F and Hou, Q and Ma, X and Hou, L},
title = {Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy.},
journal = {Cell death &amp; disease},
volume = {16},
number = {1},
pages = {49},
pmid = {39870644},
issn = {2041-4889},
support = {82070984, 82371081//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Epithelial-Mesenchymal Transition/genetics ; *Vitreoretinopathy, Proliferative/pathology/metabolism/genetics ; Animals ; Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism ; Disease Models, Animal ; *DNA-Binding Proteins/metabolism/genetics ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism ; },
abstract = {Epithelial-to-mesenchymal transition (EMT) is a critical and complex process involved in normal embryonic development, tissue regeneration, and tumor progression. It also contributes to retinal diseases, such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Although absent in melanoma 2 (AIM2) has been linked to inflammatory disorders, autoimmune diseases, and cancers, its role in the EMT of the retinal pigment epithelium (RPE-EMT) and retinal diseases remains unclear. The present study demonstrated that AIM2 functions as a potent suppressor of RPE cell proliferation and EMT to maintain retinal homeostasis. Transcriptome analysis using RNA-sequencing (RNA-Seq) revealed that AIM2 was significantly downregulated in primary human RPE (phRPE) cells undergoing EMT and proliferation. Consequently, Aim2-deficient mice showed morphological changes and increased FN expression in RPE cells under physiological conditions, whereas AIM2 overexpression in phRPE cells inhibited EMT. In a retinal detachment-induced PVR mouse model, AIM2 deficiency promotes RPE-EMT, resulting in severe experimental PVR. Clinical samples further confirmed the downregulation of AIM2 in the PVR membranes from patients. Kyoto Encyclopedia of Genes and Genome analysis revealed that the PI3K-AKT signaling pathway was significantly related to RPE-EMT and that AIM2 inhibited AKT activation in RPE cells by reducing its phosphorylation. Moreover, treatment with eye drops containing an AKT inhibitor alleviated RPE-EMT and the severity of experimental PVR. These findings provide new insights into the complex mechanisms underlying RPE-EMT and PVR pathogenesis, with implications for rational strategies for potential therapeutic applications in PVR by targeting RPE-EMT.},
}
@article {pmid39870171,
year = {2025},
author = {Charbel Issa, P and De Silva, SR and Pfau, K and Birtel, J},
title = {[Correction: Differential diagnosis of age-related macular degeneration].},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {1},
pages = {e1},
doi = {10.1055/a-2524-5086},
pmid = {39870171},
issn = {1439-3999},
}
@article {pmid39869549,
year = {2025},
author = {Kiel, C and Prins, S and Foss, AJE and Luthert, PJ},
title = {"Energetics of the outer retina II: Calculation of a spatio-temporal energy budget in retinal pigment epithelium and photoreceptor cells based on quantification of cellular processes".},
journal = {PloS one},
volume = {20},
number = {1},
pages = {e0311169},
pmid = {39869549},
issn = {1932-6203},
mesh = {*Energy Metabolism ; *Retinal Pigment Epithelium/metabolism/cytology ; Humans ; Adenosine Triphosphate/metabolism ; Circadian Rhythm ; Light ; },
abstract = {The outer retina (OR) is highly energy demanding. Impaired energy metabolism combined with high demands are expected to cause energy insufficiencies that make the OR susceptible to complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used to calculate the ATP expenditure of the main energy-consuming processes in three cell types of the OR for the night and two different periods during the day. The predicted energy demands in a rod dominated (perifovea) area are 1.69 x 1013 ATP/s/mm2 tissue in the night and 6.53 x 1012 ATP/s/mm2 tissue during the day with indoor light conditions. For a cone-dominated foveal area the predicted energy demands are 6.41 x 1012 ATP/s/mm2 tissue in the night and 6.75 x 1012 ATP/s/mm2 tissue with indoor light conditions during daytime. We propose the likely need for diurnal/circadian shifts in energy demands to efficiently stagger all energy consuming processes. Our data provide insights into vulnerabilities in the aging OR and suggest that diurnal constraints may be important when considering therapeutic interventions to optimize metabolism.},
}
@article {pmid39868215,
year = {2025},
author = {Xin, Y and Jin, Y and Qian, C and Blackshaw, S and Qian, J},
title = {MetaLigand: A database for predicting non-peptide ligand mediated cell-cell communication.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.01.14.633094},
pmid = {39868215},
issn = {2692-8205},
support = {R01 MH126676/MH/NIMH NIH HHS/United States ; },
abstract = {Non-peptide ligands (NPLs), including lipids, amino acids, carbohydrates, and non-peptide neurotransmitters and hormones, play a critical role in ligand-receptor-mediated cell-cell communication, driving diverse physiological and pathological processes. To facilitate the study of NPL-dependent intercellular interactions, we introduce MetaLigand, an R-based and web-accessible tool designed to infer NPL production and predict NPL-receptor interactions using transcriptomic data. MetaLigand compiles data for 233 NPLs, including their biosynthetic enzymes, transporter genes, and receptor genes, through a combination of automated pipelines and manual curation from comprehensive databases. The tool integrates both de novo and salvage synthesis pathways, incorporating multiple biosynthetic steps and transport mechanisms to improve prediction accuracy. Comparisons with existing tools demonstrate MetaLigand's superior ability to account for complex biogenesis pathways and model NPL abundance across diverse tissues and cell types. Furthermore, analysis of single-nucleus RNA-seq datasets from age-related macular degeneration samples revealed that distinct retinal cell types exhibit unique NPL profiles and participate in specific NPL-mediated pathological cell-cell interactions. Finally, MetaLigand supports single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data, enabling the visualization of predicted NPL production levels and heterogeneity at single-cell resolution.},
}
@article {pmid39867345,
year = {2025},
author = {Datseris, I and Rouvas, A and Tzanidaki, ME and Kardara, M and Geros, V and Gouliopoulos, N},
title = {Resveratrol Supplementation in Wet AMD: Association With Fewer Intravitreal Injections and Reduced Macular Fibrosis.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {217-225},
pmid = {39867345},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the 2-year outcomes of resveratrol oral supplement given as an adjunctive treatment in patients with wet age-related macular degeneration (AMD) that were treated with intravitreal injections of aflibercept.<br><br>PATIENTS AND METHODS: In our retrospective study, 50 treatment-na&#xef;ve patients suffering from wet-AMD were included. They were assigned to two subgroups of 25 patients each. Every participant was treated according to "Pro Re Nata" protocol; 3 monthly intravitreal injections of 2.0 mg aflibercept were applied followed by injections according to need. The patients in the second group also consumed daily two tablets of resveratrol enriched oral supplement (60 mg of resveratrol in total). For 2 years, the patients were monthly assessed with best corrected visual acuity (BCVA) measurement, fundus autofluorescence, optical coherence tomography (OCT) scans and OCT-angiography. The main endpoints were the change of BCVA, the number of anti-VEGF injections, the change of central foveal thickness values, and the expansion or new development of fibrosis.<br><br>RESULTS: Between the studied groups, no significant differences were detected in the baseline demographic and clinical data (p>0.05 for all). Over the 24-month study period, both BCVA and central foveal thickness values did not differ significantly between the two groups. As for the number of applied injections, they were significantly fewer in the group of patients that were treated with the resveratrol supplement (9.32&#xb1;1.37 vs 7.40&#xb1;1.88, p<0.001). Notably, the frequency of fibrosis progression was significantly lower in the resveratrol group (p=0.04).<br><br>CONCLUSION: In conclusion, our findings suggest that resveratrol oral supplement could be considered as a useful adjunctive aid to the established treatment in cases suffering from wet AMD, highlighting the superiority of the combination treatment regimen, since it was accompanied by lower rates of both intravitreal aflibercept injections and progression of macular fibrosis.},
}
@article {pmid39866344,
year = {2025},
author = {Elsawy, A and Keenan, TDL and Thavikulwat, AT and Lu, A and Bellur, S and Mukherjee, S and Agron, E and Chen, Q and Chew, EY and Lu, Z},
title = {Deep-Reticular Pseudodrusen-Net: A 3-Dimensional Deep Network for Detection of Reticular Pseudodrusen on OCT Scans.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100655},
pmid = {39866344},
issn = {2666-9145},
support = {K99 LM014024/LM/NLM NIH HHS/United States ; },
abstract = {OBJECTIVE: To propose Deep-RPD-Net, a 3-dimensional deep learning network with semisupervised learning (SSL) for the detection of reticular pseudodrusen (RPD) on spectral-domain OCT scans, explain its decision-making, and compare it with baseline methods.<br><br>DESIGN: Deep learning model development.<br><br>PARTICIPANTS: Three hundred fifteen participants from the Age-Related Eye Disease Study 2 Ancillary OCT Study (AREDS2) and 161 participants from the Dark Adaptation in Age-related Macular Degeneration Study (DAAMD).<br><br>METHODS: Two datasets comprising of 1304 (826 labeled) and 1479 (1366 labeled) OCT scans were used to develop and evaluate Deep-RPD-Net and baseline models. The AREDS2 RPD labels were transferred from fundus autofluorescence images, which were captured at the same visit for OCT scans, and DAAMD RPD labels were obtained from the Wisconsin reading center. The datasets were divided into 70%, 10%, and 20% at the participant level for training, validation, and test sets, respectively, for the baseline model. Then, SSL was used with the unlabeled OCT scans to improve the trained model. The performance of Deep-RPD-Net was compared to that of 3 retina specialists on a subset of 50 OCT scans for each dataset. En face and B-scan heatmaps of all networks were visualized and graded on 25 OCT scans with positive labels, using a scale of 1 to 4, to explore the models' decision-making.<br><br>MAIN OUTCOME MEASURES: Accuracy and area under the receiver-operating characteristic curve (AUROC).<br><br>RESULTS: Deep-RPD-Net achieved the highest performance metrics, with accuracy and AUROC of 0.81 (95% confidence interval [CI]: 0.76-0.87) and 0.91 (95% CI: 0.86-0.95) on the AREDS2 dataset and 0.80 (95% CI: 0.75-0.84) and 0.86 (95% CI: 0.79-0.91) on the DAAMD dataset. On the subjective test, it achieved accuracy of 0.84 compared with 0.76 for the most accurate retina specialist on the AREDS2 dataset and 0.82 compared with 0.84 on the DAAMD dataset. It also achieved the highest visualization grades, of 3.26 and 3.32 for en face and B-scan heatmaps, respectively.<br><br>CONCLUSIONS: Deep-RPD-Net was able to detect RPD accurately from OCT scans. The visualizations of Deep-RPD-Net were the most explainable to the retina specialist with the highest accuracy. The code and pretrained models are publicly available at https://github.com/ncbi-nlp/Deep-RPD-Net.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39865322,
year = {2025},
author = {Miller, A and Macnaughton, J and Crossland, MD and Latham, K},
title = {'Such a lot of bother': Qualitative results of a home trial of a wearable electronic vision enhancement system for people with age-related macular degeneration.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {3},
pages = {699-712},
pmid = {39865322},
issn = {1475-1313},
support = {//Macular Society/ ; },
mesh = {Humans ; Female ; Male ; *Wearable Electronic Devices ; Aged, 80 and over ; *Macular Degeneration/physiopathology/rehabilitation ; *Visual Acuity/physiology ; Cross-Over Studies ; Aged ; *Vision, Low/rehabilitation/physiopathology/etiology ; Equipment Design ; *Sensory Aids ; Qualitative Research ; *Persons with Visual Disabilities/rehabilitation ; },
abstract = {PURPOSE: Wearable electronic low vision enhancement systems (wEVES) improve visual function but are not widely adopted by people with vision impairment. Here, qualitative research methods were used to investigate the usefulness of wEVES for people with age-related macular degeneration (AMD) after an extended home trial.<br><br>METHODS: Following a 12-week non-masked randomised crossover trial, semi-structured interviews were completed with 34 participants with AMD, 64.7% female, mean age 80.2 (&#xb1;6.0) years, mean distance visual acuity 0.81logMAR (&#xb1;0.32). Reflexive thematic analysis was used to analyse the data.<br><br>RESULTS: Four themes were developed: (i) early positivity and potential; (ii) you're not good enough: performance barriers of the device; (iii) you're annoying: practicality barriers of the device and (iv) we can fix this together. First, participants expressed joy in an aesthetically appealing device perceived as potentially enabling, different and complementary to their current solutions. Imagined usefulness included not only reading, shopping and television but also resuming abandoned hobbies. The second theme captured performance barriers that restricted numerous activities but were most acutely noted with manipulation tasks. Barriers included image quality, screen size and short-lived adverse effects. The third theme conveyed the multiple practical challenges that caused annoyance, preventing imagined usage even when performance appeared superior to other solutions. Slow start-up times and the inability to use wEVES dynamically prevented integration within users' lifestyles. The final theme reflected that wEVES remained a desirable concept, but future iterations require inclusive design methodology to ensure development is directed by consumers' needs.<br><br>CONCLUSIONS: Performance and practicality barriers limit the usefulness of a device initially seen as desirable. Current devices do not align with users' requirements for flexible use, even when performance is good. Improvements in technology may solve performance barriers, but these changes must be inclusively designed and evaluated to ensure the device integrates more successfully into the lives of users with AMD.},
}
@article {pmid39863929,
year = {2025},
author = {Schlosser, A and Pilecki, B and Allen, C and Benest, AV and Lynch, AP and Hua, J and Ved, N and Blackley, Z and Andersen, TL and Hennig, D and Graversen, JH and Möller, S and Skallerup, S and Ormhøj, M and Lange, C and Agostini, HT and Grauslund, J and Heegaard, S and Dacheva, I and Koss, M and Hu, W and Iglesias, B and Lawrence, MS and Beck, HC and Steffensen, LB and Laursen, NS and Andersen, GR and Holmskov, U and Bates, DO and Sorensen, GL},
title = {Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {33},
number = {3},
pages = {1048-1072},
pmid = {39863929},
issn = {1525-0024},
mesh = {Animals ; Mice ; Humans ; Disease Models, Animal ; *Extracellular Matrix Proteins/antagonists &amp; inhibitors/metabolism/genetics ; *Retinal Neovascularization/drug therapy/metabolism/pathology ; Capillary Permeability/drug effects ; Cell Movement/drug effects ; Choroidal Neovascularization/drug therapy/metabolism/pathology ; Endothelial Cells/metabolism/drug effects ; },
abstract = {Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αVβ3/5/6 ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell types in close proximity to vascular endothelial cells, including choroidal vascular mural cells, retinal astrocytes, and Müller cells. Binding of the anti-MFAP4 antibody, hAS0326, makes MFAP4 inaccessible for integrin receptor interaction, and thereby hAS0326 blocked endothelial cell motility in vitro. Intravitreal hAS0326 inhibited retinal vascular lesion area and neovessel volume in a laser-induced choroidal neovascularization mouse model, vascular permeability in streptozotocin-induced retinopathy, and vascular leakage area in a chronic non-human primate model of DL-2-aminoadipic acid-induced retinopathy. One dose of hAS0326 showed duration of efficacy of at least 12 weeks in the latter model. Moreover, hAS0326 treatment significantly enriched Gene Ontology terms involving reduction of integrin binding. Our data suggest that hAS0326 constitutes a promising treatment of neovascularization and vascular leakage in retinal diseases.},
}
@article {pmid39863708,
year = {2025},
author = {Nadel, A and Drakopoulos, M and Bains, HK and Bar-Meir, A and Marchese, A and Lyon, AT and Mirza, RG},
title = {Analysis of quantitative OCT and SS-OCTA metrics three months after initiation of intravitreal faricimab for treatment-recalcitrant neovascular AMD.},
journal = {Eye (London, England)},
volume = {39},
number = {7},
pages = {1337-1343},
pmid = {39863708},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Intravitreal Injections ; Male ; Female ; Aged ; Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Fluorescein Angiography/methods ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged, 80 and over ; Middle Aged ; Prospective Studies ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To utilize optical coherence tomography (OCT) and SS-OCT angiography (SS-OCTA) for quantifying morphological changes seen in eyes with recalcitrant neovascular age-related macular degeneration (nAMD) transitioned to intravitreal faricimab injections during the manufacturer's recommended induction phase of treatment.<br><br>METHODS: Fifty-four treatment-recalcitrant patients (60 eyes) were recruited. OCT and SS-OCTA images were obtained at 0 and 3 months. Best-corrected visual acuity (BCVA), OCT, pigment epithelial detachment (PED), and macular neovascularization (MNV) parameters were analyzed at baseline and 3 months.<br><br>RESULTS: Thirty-two patients (38 eyes) were included in the baseline OCT characteristic analysis, 29 patients (35 eyes) in the MNV analysis, and 18 patients (21 eyes) in the PED analysis. Significant decreases in PED parameters were observed, including PED volume (mean decrease of 0.0592 mm[3] (-19.66%; p&#x2009;=&#x2009;0.0164), sample standard deviation (ssd)&#x2009;=&#x2009;0.114&#x2009;mm[3]), mean height (mean decrease of 0.00871&#x2009;mm (-19.16%; p&#x2009;=&#x2009;0.0003), ssd&#x2009;=&#x2009;0.0143&#x2009;mm), and maximum height (mean decrease of 0.0242&#x2009;mm (-15.28%; p&#x2009;=&#x2009;0.002), ssd&#x2009;=&#x2009;0.0359). Significant decreases in MNV metrics were also observed, including area (mean decrease of 0.252&#x2009;mm[2] (-9.06%; p&#x2009;=&#x2009;0.0054), ssd&#x2009;=&#x2009;0.519&#x2009;mm[2]), and vessel area density (mean decrease of 6.51% absolute (-8.23%; p&#x2009;=&#x2009;0.0004), ssd&#x2009;=&#x2009;0.0943% absolute). BCVA (logMAR) remained stable between baseline and 3 months (0.25-0.23; p&#x2009;=&#x2009;0.34). Notably, there were no statistically significant changes in the percentage of eyes with intraretinal fluid (IRF) or subretinal fluid (SRF) between baseline and 3 months (all p&#x2009;>&#x2009;0.05).<br><br>CONCLUSIONS: In recalcitrant nAMD patients who were transitioned to faricimab, patients maintained their vision while significant improvements in OCT PED and SS-OCTA MNV parameters were seen during the induction phase.},
}
@article {pmid39863706,
year = {2025},
author = {Janmohamed, IK and Mushtaq, A and Kabbani, J and Harrow, S and Nadarajasundaram, A and Ata, A and Monye, H and Jarrar, Z and Hannan, S and Membrey, L},
title = {1-Year real-world outcomes of faricimab in previously treated neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {7},
pages = {1344-1348},
pmid = {39863706},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; Visual Acuity ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Treatment Outcome ; *Antibodies, Bispecific/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Follow-Up Studies ; Middle Aged ; Macula Lutea/pathology ; Time Factors ; },
abstract = {BACKGROUND AND OBJECTIVES: Faricimab, a bispecific antibody targeting VEGF-A and angiopoietin-2, has shown promise in treating neovascular age-related macular degeneration (nAMD). This study evaluates 1-year outcomes of faricimab in treatment-experienced nAMD patients.<br><br>METHODS: This single-centre retrospective cohort study included patients previously treated for nAMD who switched to faricimab between November 2022 and March 2024. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and treatment intervals were assessed at baseline, 6, and 12 months.<br><br>RESULTS: One hundred eighty-four patients (215 eyes) were included. Patients had received a median of 18 (interquartile range [IQR] 10-28.5) anti-VEGF injections per eye over an average of 5.02&#x2009;&#xb1;&#x2009;11.82 years before switch. An average of 8.63&#x2009;&#xb1;&#x2009;2.2 faricimab injections were administered per eye over an average follow-up of 12.19&#x2009;&#xb1;&#x2009;2.70 months. Median BCVA decreased from 70 ETDRS letters (IQR 55-76) at baseline to 62 (IQR 47-76) at 12 months (p&#x2009;=&#x2009;0.0038). Median CMT improved from 259.5 &#x3bc;m (IQR 223-299.75) at baseline to 232 &#x3bc;m (202.0-272.5) at 12 months (p&#x2009;<&#x2009;0.0001). At the last follow-up, 40.2% of eyes were dry on OCT. The median dosing interval doubled from 4 weeks (IQR 4-4) to 8 weeks (IQR 6-10) with faricimab (p&#x2009;<&#x2009;0.0001). 47.4% and 16.3% of eyes achieved treatment intervals of &#x2265;8-12 weeks and &#x2265;12 weeks, respectively. Three events of uveitis were noted following the loading phase.<br><br>CONCLUSIONS: This real-world study demonstrates that faricimab maintains vision and achieves significant anatomical improvements in treatment-experienced nAMD patients. The extended treatment intervals could significantly reduce the burden on patients and healthcare resources.},
}
@article {pmid39863057,
year = {2025},
author = {Allan, KC and Joo, JH and Kim, S and Shaia, J and Kaelber, DC and Singh, R and Talcott, KE and Rachitskaya, AV},
title = {Glucagon-like Peptide-1 Receptor Agonist Impact on Chronic Ocular Disease Including Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {132},
number = {7},
pages = {748-757},
doi = {10.1016/j.ophtha.2025.01.016},
pmid = {39863057},
issn = {1549-4713},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; Aged ; *Glucagon-Like Peptide-1 Receptor Agonists ; *Hypoglycemic Agents/therapeutic use ; Middle Aged ; *Glaucoma, Open-Angle/epidemiology/drug therapy ; Chronic Disease ; Metformin/therapeutic use ; Aspirin/therapeutic use ; Aged, 80 and over ; Risk Factors ; Ocular Hypertension/epidemiology ; *Wet Macular Degeneration/epidemiology ; *Macular Degeneration/epidemiology ; Cataract/epidemiology ; Follow-Up Studies ; United States/epidemiology ; Electronic Health Records ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Insulin/therapeutic use ; },
abstract = {PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to exert neuroprotective and anti-inflammatory effects across multiple organ systems. This study investigated whether GLP-1RAs influence the risk for age-related ocular diseases.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: This study used an electronic health records platform of patients in the United States. Patients > 60 years with at least 5 years of ophthalmology follow-up and medication prescription documentation were included. There were 5 medication groups: GLP-1RA, metformin, insulin, statin, or aspirin users. Cohorts were propensity matched (1:1) on demographics and chronic disease risk factors.<br><br>MAIN OUTCOME MEASURES: Outcomes of cataract, ocular hypertension, primary open-angle glaucoma, nonexudative age-related macular degeneration (AMD), and exudative AMD were compared 5 years after initial medication prescription. We then examined earlier time points within the 5-year period. Significance was defined as P < 0.05 with a hazard ratio (HR) threshold of > 1.1 or < 0.9.<br><br>RESULTS: Of the 9669 patients taking GLP-1RAs, 84.4% had a diagnosis of diabetes with an average body mass index (BMI) of 36.2 kg/m[2]. Propensity-matched cohorts demonstrated that GLP-1RAs were associated with a reduced hazard of nonexudative AMD compared with metformin (HR, 0.68; 95% CI, 0.56-0.84), insulin (HR, 0.72; 95% CI, 0.58-0.89), and statins (HR, 0.70; 95% CI, 0.57-0.87). These findings were validated compared with aspirin and in an independent older cohort of patients. This significant reduction appeared after 3 years compared with metformin (HR, 0.69; 95% CI, 0.52-0.91), insulin (HR, 0.66; 95% CI, 0.5-0.87), and statins (HR, 0.67; 95% CI, 0.51-0.88). Time course results were validated using independent cohorts of propensity-matched patients taking medications for 3 years. Notably, GLP-1RAs also significantly reduced the risk of exudative AMD (HR, 0.70; 95% CI, 0.58-0.84) and primary open-angle glaucoma (HR, 0.58; 95% CI, 0.45-0.76) compared with insulin after 3 years. Use of GLP-1RAs showed no persistent impact on the risk of cataract formation or ocular hypertension compared with other medications.<br><br>CONCLUSIONS: This study suggests that GLP-1RAs may reduce the risk of multiple age-related ocular diseases and the need for future prospective studies to validate these findings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39861733,
year = {2025},
author = {Martinez, SM and Inda, A and Ríos, MN and Bessone, CDV and Bruera Bossio, A and Guido, ME and Luna Pinto, JD and Allemandi, DA and Quinteros, DA},
title = {Neuroprotective Effect of Melatonin Loaded in Human Serum Albumin Nanoparticles Applied Subconjunctivally in a Retinal Degeneration Animal Model.},
journal = {Pharmaceutics},
volume = {17},
number = {1},
pages = {},
pmid = {39861733},
issn = {1999-4923},
support = {PIP 2022-2024-GI//Consejo Nacional de Investigaciones Cient&#xed;ficas y T&#xe9;cnicas/ ; FONCyT; Grant number PICT-2021-I-A-01195//Agencia Nacional de Promoci&#xf3;n de la Investigaci&#xf3;n, el Desarrollo Tecnol&#xf3;gico y la Innovaci&#xf3;n/ ; },
abstract = {BACKGROUND/OBJECTIVES: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina.<br><br>METHODS: A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index.<br><br>RESULTS: Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel.<br><br>CONCLUSIONS: Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies.},
}
@article {pmid39861461,
year = {2025},
author = {Yeh, WJ and Yan, C and Wu, CH},
title = {Photoprotective Effects of Phytochemicals on Blue Light-Induced Retinal Damage: Current Evidence and Future Perspectives.},
journal = {Nutrients},
volume = {17},
number = {2},
pages = {},
pmid = {39861461},
issn = {2072-6643},
support = {NSTC 112-2320-B-003-001//National Science and Technology Council, Taiwan./ ; NSTC 113-2320-B-003-002-MY3//National Science and Technology Council, Taiwan./ ; },
mesh = {Humans ; *Phytochemicals/pharmacology ; *Light/adverse effects ; Animals ; Antioxidants/pharmacology ; *Retina/radiation effects/drug effects/metabolism ; Oxidative Stress/drug effects ; *Retinal Diseases/prevention &amp; control/etiology ; Macular Degeneration/prevention &amp; control/etiology ; Reactive Oxygen Species/metabolism ; Blue Light ; },
abstract = {The widespread use of light-emitting diodes (LEDs) has increased blue light (BL) exposure, raising concerns about its potential adverse effects on ocular health. Prolonged exposure to BL has been implicated in the pathogenesis of various retinal disorders, including age-related macular degeneration (AMD), primarily through mechanisms involving oxidative stress and inflammation mediated by the overproduction of reactive oxygen species (ROS). This review synthesizes current evidence on the photoprotective properties of dietary bioactive compounds, (e.g., anthocyanins, curcumin, quercetin, myricetin, and resveratrol), with a focus on their potential to mitigate BL-induced retinal damage. Accumulating research suggests that dietary antioxidants, particularly polyphenols, may offer photoprotective benefits. These phytochemicals act by neutralizing ROS and enhancing the retina's endogenous antioxidant capacity. Based on these findings, this review advocates for a food-first approach in future investigations, emphasizing the development of evidence-based dietary recommendations to bolster retinal health and mitigate the risk of BL-related ocular diseases. Considering the current lack of empirical clinical studies examining the impact of BL on human ocular health, future research in the field of BL hazard should prioritize two key approaches: conducting large-scale epidemiological dietary surveys and implementing clinical trials on functional ingredients that have demonstrated beneficial effects against photodamage in preclinical animal studies.},
}
@article {pmid39860565,
year = {2025},
author = {Camacho, P and Ribeiro, E and Pereira, B and Nascimento, J and Caldeira Rosa, P and Henriques, J and Barrão, S and Sadio, S and Quendera, B and Delgadinho, M and Ginete, C and Silva, C and Brito, M},
title = {DNA Methyltransferase Expression (DNMT1, DNMT3a, and DNMT3b) as a Potential Biomarker in Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {2},
pages = {},
pmid = {39860565},
issn = {2077-0383},
support = {IDI&amp;CA grant IPL/IDI&amp;CA2023/DETECTnAMD_ESTESL, by H&amp;TRC- Health &amp; Technology Research Center, ESTeSL//Instituto Polit&#xe9;cnico de Lisboa/ ; FCT/MCTES UIDB/05608/2020, UIDP/05608/2020//the Retina Institute of Lisbon (IRL)/ ; },
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a global cause of vision loss, with limited therapeutic options highlighting the need for effective biomarkers. This study aimed to characterize plasma DNA methyltransferase expression (DNMT1, DNMT3A, and DNMT3B) in AMD patients and explore divergent expression patterns across different stages of AMD. Methods: Thirty-eight AMD patients were prospectively enrolled and stratified by disease severity: eAMD, iAMD, nAMD, and aAMD. Comprehensive ophthalmological assessments were performed, including best-corrected visual acuity, digital color fundus photographs, and Spectral Domain Optical Coherence Tomography. Peripheral blood samples were collected for RNA extraction and qRT-PCR to access epigenetic effectors' transcriptional expression, namely DNMT1, DNMT3A, and DNMT3B genes. The collected data were analyzed using IBM SPSS 29. Results:DNMT1 expression was significantly downregulated in late AMD (-0.186 ± 0.341) compared to early/intermediate AMD (0.026 ± 0.246). Within late AMD, aAMD exhibited a marked downregulation of DNMT1 (-0.375 ± 0.047) compared to nAMD (0.129 ± 0.392). DNMT3A and DNMT3B showed similar divergent expression patterns, correlating with disease stage. Conclusions: This study identified stage-specific transcriptional differences in DNMT expression, emphasizing its potential as a biomarker for AMD progression and a target for future research into personalized therapeutic strategies.},
}
@article {pmid39860453,
year = {2025},
author = {Nowak, M and Cybulska, AM and Schneider-Matyka, D and Grochans, E and Walaszek, I and Panczyk, M and Nowicki, GJ and Rachubińska, K},
title = {Acceptance of the Disease in Patients Diagnosed with Neovascular Age-Related Macular Degeneration Depending on Visual Parameters-Before and After a Series of Seven Intravitreal Injections.},
journal = {Journal of clinical medicine},
volume = {14},
number = {2},
pages = {},
pmid = {39860453},
issn = {2077-0383},
abstract = {Background: Age-related macular degeneration (AMD) is a progressive, chronic eye disease with no permanent cure currently available. Symptoms of the disease, including distorted and blurred vision and gradual loss of central vision, significantly aggravate patients' daily functioning. The purpose of this study was to assess the acceptance of the disease among patients diagnosed with neovascular age-related macular degeneration before treatment and after receiving seven intravitreal injections and to determine how it was related to the values of visual parameters. Methods: This survey-based study was carried out using the author's questionnaire and a standardized research tool, the Acceptance of Illness Scale (AIS). It also involved the analysis of the patients' medical records. Results: The study included 121 patients (121 eyes), including 60 women and 61 men. The age range of the participants was 51-90 years. The mean and median age of the participants was 75 years. After undergoing a series of intravitreal injections, statistically significant improvements were observed in the degree of illness acceptance according to the AIS score. Data analysis revealed that the degree of disease acceptance was significantly related to visual acuity and contrast sensitivity. Conclusions: The acceptance of the disease among the study participants from the beginning of the therapy until receiving a series of seven intravitreal injections was at an average level. Acceptance of the disease was better before the beginning of the therapy, due to higher values of corrected visual acuity, and after the therapy, because of higher values of contrast sensitivity and corrected visual acuity.},
}
@article {pmid39860429,
year = {2025},
author = {Wolfrum, P and Böhm, EW and Lorenz, K and Stoffelns, B and Pfeiffer, N and Korb, CA},
title = {Clinical Outcomes Following a Switch of Therapy to Faricimab in Patients Affected by Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {14},
number = {2},
pages = {},
pmid = {39860429},
issn = {2077-0383},
abstract = {Objectives: In this study, we evaluated clinical outcomes following a therapy switch to Faricimab, in a patient cohort affected by neovascular age-related macular degeneration (nAMD), having received prior intravitreal anti-VEGF therapy. Methods: A retrospective investigation, including 28 eyes of 23 patients, treated for nAMD at the University Medical Center Mainz, Germany was performed. A switch in therapy to Faricimab was conducted, due to an inadequate response to the previous anti-VEGF treatment. Visual acuity (VA), central retinal thickness (CRT), and axial pigment epithelial detachment (PED) height were analyzed, following the first (FU 1) and second (FU 2) Faricimab injection series. Further, a subgroup analysis was conducted to compare Faricimab responders and diminished responders, as well as an exploratory data analyses to evaluate potential influencing factors on VA and CRT changes. Results: The mean age of patients was 82 years, with an average prior anti-VEGF treatment duration of 4.4 years and an average of 33 prior injections. Following Faricimab, at FU 1, significant reductions in CRT (from 335.8 µm to 260.0 µm, p < 0.01) and axial PED height (from 177 µm to 116 µm, p < 0.01) were observed. At FU 2, anatomical improvements were stable. No significant improvements in VA were observed, with LogMAR remaining stable at FU 1 and FU 2. In the subgroup comparison, eight eyes fulfilled the responder criteria, exhibiting morphological and functional improvements following intravitreal Faricimab. Further, a bigger baseline CRT correlated with a bigger post-treatment CRT and a longer prior treatment duration, and a worse baseline VA correlated with a worse post-Faricimab VA. No adverse events were noted following the switch to Faricimab. Conclusions: Following a switch to Faricimab, significant anatomical improvements were observed, while VA remained stable. Baseline CRT, prior treatment duration, and baseline LogMAR were associated with clinical outcomes post the switch to Faricimab. Further investigations into long-term outcomes are necessary to evaluate the sustained efficacy of Faricimab.},
}
@article {pmid39860127,
year = {2025},
author = {Lin, S and Tang, RW and Ye, Y and Xia, C and Wu, J and Duan, R and Leung, KW and Dong, TT and Tsim, KW},
title = {Drug Screening of Flavonoids as Potential VEGF Inhibitors Through Computational Docking and Cell Models.},
journal = {Molecules (Basel, Switzerland)},
volume = {30},
number = {2},
pages = {},
pmid = {39860127},
issn = {1420-3049},
mesh = {*Flavonoids/pharmacology/chemistry ; Humans ; *Molecular Docking Simulation ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/chemistry/metabolism ; Drug Evaluation, Preclinical ; Cell Line ; NF-kappa B/metabolism ; Macrophages/drug effects/metabolism ; },
abstract = {Vascular endothelial growth factor (VEGF), also known as VEGF-A, has been linked to various diseases, such as wet age-related macular degeneration (wAMD) and cancer. Even though there are VEGF inhibitors that are currently commercially available in clinical applications, severe adverse effects have been associated with these treatments. There is still a need to develop novel VEGF-based therapeutics against these VEGF-related diseases. Here, we established a series of VEGF-based computational docking analyses and cell models, such as a wound healing assay in HaCaT cells and an evaluation of NF-κB performance in macrophages, to screen a large library of flavonoid-type phytochemicals. Three flavonoids, namely, farrerol, ononin and (-)-epicatechin, were shown to express binding affinities to VEGF protein and inhibit VEGF-mediated biological activities. The investigation evidently suggested that the three flavonoids above could be considered potential anti-VEGF agents for the following drug development against VEGF-mediated diseases.},
}
@article {pmid39859971,
year = {2024},
author = {Vitiello, L and De Bernardo, M and De Pascale, I and Salerno, G and Pellegrino, A and Rosa, N},
title = {Postpartum Exudation of Idiopathic Quiescent Macular Neovascularization: A Narrative Review with a Related Case Report.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {1},
pages = {},
pmid = {39859971},
issn = {2075-1729},
abstract = {The abnormal growth of irregular new blood vessels into the subretinal or intraretinal space is known as macular neovascularization (MNV). People over 50 are often affected by this disorder, which is typically brought on by age-related macular degeneration. In addition, MNV can be found in people under 50 years of age, who may present primary ophthalmic diseases such as pathological myopia, angioid streaks, traumatic choroidal rupture, or suspected ocular histoplasmosis syndrome. However, it is important to consider a specific set of young individuals who may develop MNV even in the absence of pathological myopia or other identifiable inflammatory, peripapillary, post-traumatic, or degenerative fundus abnormalities. This latter condition is classified as idiopathic MNV. After a literature review focused on young patients affected by one of these two clinical entities, we report the case of a Caucasian young woman suffering for four years from an idiopathic and quiescent MNV that started exuding after childbirth, probably due to the induction with oxytocin, and was treated with intravitreal Aflibercept 2 mg injections.},
}
@article {pmid39859107,
year = {2025},
author = {Kazantzis, D and Machairoudia, G and Theodossiadis, P and Chatziralli, I},
title = {The Neutrophil to Lymphocyte Ratio and Other Full Blood Count Indices in Retinal Diseases: A Systematic Review of the Literature.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {1},
pages = {},
pmid = {39859107},
issn = {1648-9144},
mesh = {Humans ; *Neutrophils ; *Lymphocytes ; *Retinal Diseases/blood/physiopathology ; Biomarkers/blood/analysis ; Diabetic Retinopathy/blood ; Blood Cell Count/methods ; },
abstract = {Background and Objectives: The neutrophil to lymphocyte ratio (NLR) and other full blood count indices have been used as a marker of inflammation in a variety of diseases. The aim of the current review is to summarize the existing knowledge on the use of these indices in retinal diseases. Materials and Methods: A systematic review of the literature was conducted to find eligible articles. The PUBMED and Scopus databases were systematically searched for relevant studies examining full blood count indices in retinal diseases. Results: The NLR was elevated in a number of vitreoretinal conditions, such as wet age-related macular degeneration (AMD), diabetic retinopathy and retinal vein occlusion, compared to controls. Full blood count indices could be useful in predicting the response to anti-VEG treatment in patients with wet AMD or diabetic macular edema (DME). Conclusions: The NLR and other indices can be used as diagnostic markers in retinal diseases and as prognostic factors of the response to treatment. The small sample size and short follow-up of the included studies and the variation in the measurement and cutoffs used for the NLR are limitations of its use in retinal conditions. Future studies need to further validate these findings and try to establish a link between these ratios and retinal phenotypes.},
}
@article {pmid39857340,
year = {2024},
author = {Zeppieri, M and Gagliano, C and D'Esposito, F and Musa, M and Gattazzo, I and Zanella, MS and Rossi, FB and Galan, A and Babighian, S},
title = {Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA): A Targeted Antioxidant Strategy to Counter Oxidative Stress in Retinopathy.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {1},
pages = {},
pmid = {39857340},
issn = {2076-3921},
abstract = {Omega-3 fatty acids are critical components of cell membranes, including those in the retina. Specifically, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the primary omega-3 fatty acids that have been studied for their potential benefits in retinal health, preventing the progression of retinopathy. Several studies have shown that a higher intake of omega-3 fatty acids is associated with a lower risk of developing diabetic retinopathy and age-related macular degeneration (AMD). Reviewing clinical trials and observational studies that support the protective role of omega-3s in retinal disorders is essential. This comprehensive review aims to evaluate the current literature on the role of omega-3 fatty acids, exploring their mechanisms of action and anti-inflammatory, anti-angiogenic, and neuroprotective roles in the retina. Omega-3s have been shown to inhibit abnormal blood vessel growth in the retina, which is a significant factor in proliferative diabetic retinopathy and neovascular AMD. Furthermore, omega-3 fatty acids are often studied with other nutrients, such as lutein, zeaxanthin, and vitamins, for their synergistic effects on retinal health. Reviewing these combinations can help understand how omega-3s can be part of a comprehensive approach to preventing or treating retinopathies, especially in diabetic patients. This review emphasizes the preventive function of EPA and DHA in alleviating oxidative stress-related damage in retinal diseases, concentrating on their antioxidative mechanisms.},
}
@article {pmid39856428,
year = {2025},
author = {Bikbov, MM and Kazakbaeva, GM and Rakhimova, EM and Panda-Jonas, S and Tuliakova, AM and Fakhretdinova, AA and Jonas, JB},
title = {Mortality and ocular parameters and diseases.},
journal = {Eye (London, England)},
volume = {39},
number = {7},
pages = {1322-1331},
pmid = {39856428},
issn = {1476-5454},
mesh = {Humans ; Male ; Female ; Aged, 80 and over ; Aged ; Middle Aged ; Adult ; *Eye Diseases/mortality ; Risk Factors ; Visual Acuity/physiology ; Prevalence ; Cause of Death/trends ; Follow-Up Studies ; Diabetic Retinopathy/mortality ; },
abstract = {BACKGROUND: To assess associations between mortality and major ocular parameters and diseases.<br><br>METHODS: The population-based Ural Eye and Medical Study (UEMS) and Ural Very Old Study (UVOS) included 5899 individuals (age: 40+ years) and 1526 individuals (age: 85+ years), respectively. Cause-specific mortality was determined using the government regional information and analytical system.<br><br>RESULTS: In the UEMS, 689 (11.7%) participants had died during the follow-up of 7.0&#x2009;&#xb1;&#x2009;0.4 years (median: 6.9 years). Higher death occurrence was associated (multivariable analysis) with lower best corrected visual acuity (OR: 1.86; 95%CI:1.10, 2.68) and higher prevalence of diabetic retinopathy (OR: 2.97; 95%CI: 1.68, 5.26), with adjusting for older age (OR: 1.08), male sex (OR: 4.18), higher waist-hip ratio (OR: 5.53), current smoking (OR: 2.25), history of cancer (OR: 1.93) and dementia (OR: 2.54), higher serum concentration of glucose (OR: 1.13) and lower serum concentration of high-density lipoproteins (OR: 0.89) and haemoglobin (OR: 0.99), higher leucocyte count (OR: 1.07), higher prevalence of chronic obstructive pulmonary disease (OR: 1.67), higher stage of arterial hypertension (OR: 1.15), and higher depression score (OR: 1.04). Death occurrence was not significantly associated with prevalence of age-related macular degeneration (P&#x2009;=&#x2009;0.90), macular reticular pseudodrusen (P&#x2009;=&#x2009;0.90), open-angle glaucoma (P&#x2009;=&#x2009;0.11), angle-closure glaucoma (P&#x2009;=&#x2009;0.98), nuclear cataract (P&#x2009;=&#x2009;0.07), cortical cataract (P&#x2009;=&#x2009;0.46), axial length (P&#x2009;=&#x2009;0.44) and intraocular pressure (P&#x2009;=&#x2009;0.87). In the UVOS, 791 (51.9%) participants had died during the follow-up of 4.8&#x2009;&#xb1;&#x2009;1.0 years (median: 5.2 years). None of the ophthalmological parameters was significantly associated with death occurrence.<br><br>CONCLUSIONS: Diabetic retinopathy was the only major ophthalmic disease or parameter, in addition to vision impairment, which was associated with an increased death risk.},
}
@article {pmid39855645,
year = {2025},
author = {Beros, AL and Sluyter, JD and Scragg, R},
title = {Association of arterial stiffness and eye disease: a systematic review and meta-analysis.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {39855645},
issn = {2397-3269},
mesh = {Humans ; *Vascular Stiffness/physiology ; Pulse Wave Analysis ; *Glaucoma/physiopathology ; *Macular Degeneration/physiopathology ; *Retinal Vein Occlusion/physiopathology ; *Eye Diseases/physiopathology ; },
abstract = {BACKGROUND: This systematic review and meta-analysis assesses the association of arterial stiffness with age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO) and retinopathy (diabetic and hypertensive).<br><br>METHODS: Medline and Embase were systematically searched for observational studies of arterial stiffness and eye disease. Cohort studies were included if they estimated arterial stiffness using any measures based on the arterial waveform, with cross-sectional and case-control studies limited to measures of pulse wave velocity. We assessed the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation.<br><br>RESULTS: The systematic review of 61 studies (six for AMD, ten for glaucoma, six for RVO and 39 for retinopathy) showed that arterial stiffness overall was higher in people with eye disease than people without eye disease. Forty-four cross-sectional and case-control studies were included in the meta-analysis. Arterial stiffness estimated by way of pulse wave velocity was associated with AMD (mean difference: 0.92 m/s, 95% CI 0.37 to 1.46; 2 studies; n=381; low certainty evidence), glaucoma (mean difference: 0.97 m/s, 95% CI 0.31 to 1.64; 7 studies; n=3418; low certainty evidence), RVO (mean difference: 2.79 m/s, 95% CI 2.02 to 3.55; 5 studies; n=414; very low certainty evidence) and retinopathy (1.48 m/s, 95% CI 0.1.16 to 1.81; 22 studies; n=10&#x2009;074; low certainty evidence). The 19 cohort studies identified (five for AMD, three for glaucoma, one for RVO and 10 for retinopathy) indicated overall that increased arterial stiffness was associated with the future development of eye disease.<br><br>CONCLUSIONS: Higher arterial stiffness is associated with AMD, glaucoma, RVO and retinopathy PROSPERO REGISTRATION NUMBER: CRD42019129563.},
}
@article {pmid39855606,
year = {2025},
author = {Sadeghi, E and Rahmanipour, E and Valsecchi, N and Kapoor, S and Cicinelli, MV and Chhablani, J},
title = {An update on ocular effects of antidiabetic medications.},
journal = {Survey of ophthalmology},
volume = {70},
number = {4},
pages = {704-712},
doi = {10.1016/j.survophthal.2025.01.010},
pmid = {39855606},
issn = {1879-3304},
mesh = {Humans ; *Hypoglycemic Agents/adverse effects/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetic Retinopathy/drug therapy ; *Eye Diseases/chemically induced ; },
abstract = {The global increase in the prevalence of type 2 diabetes has led to the development and implementation of new classes of antidiabetic medications, introducing advanced therapeutic options for the management of the disease. These new medications, though primarily designed to regulate blood glucose levels, also have applications in weight management, potentially transforming the current approaches to diabetes treatment. Newer medications, however, have ophthalmic side effects with controversies in trials and real-life data. We comprehensively assessed the ocular benefits and adverse effects of traditional and newer-generation anti-diabetic drugs. Our primary focus is on how these newer medications affect the stage of diabetic retinopathy. Additionally, we explore the associations between these medications and other ocular conditions, including age-related macular degeneration, glaucoma, orbital conditions, and diseases impacting the ocular surface. Furthermore, we provide contextual background by discussing the ocular effects of traditional anti-diabetic drugs.},
}
@article {pmid39854159,
year = {2025},
author = {Torkashvand, A and Hajrasouliha, A},
title = {Exosome's Implications in Age-Related Macular Degeneration.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/02713683.2025.2457105},
pmid = {39854159},
issn = {1460-2202},
abstract = {PURPOSE: This study aims to conduct a mini review of published literature concerning the role of exosomes in the field of ophthalmology, with a specific focus on Age-Related Macular Degeneration (AMD).<br><br>METHODS: In this study, a comprehensive search was conducted using PubMed and Google Scholar to identify relevant publications. Additionally, trials submitted to clinicaltrials.gov were reviewed to identify further relevant articles. The selected studies specifically focused on the ocular implications of exosomes in Age-Related Macular Degeneration.<br><br>RESULTS: Exosomes, small extracellular vesicles measuring less than 200&#x2009;nm, play a crucial role in cell signaling and are involved in various physiological and pathological processes. Recent research has focused on utilizing exosomes for disease detection and treatment. Studies have investigated the ocular implications of exosomes, particularly in AMD. Exosomes found in aqueous fluid and blood have been examined as potential markers for AMD and as indicators of treatment response. Additionally, research in animal models has indicated the potential of exosomes in preventing AMD, as well as their promise for targeted and efficient drug delivery. This mini review primarily emphasizes the clinical aspects of publications related to AMD, rather than focusing solely on basic science.<br><br>CONCLUSIONS: Exosomes have a great potential for understanding Age-related Macular Degeneration and effective and targeted treatment for retinal diseases.},
}
@article {pmid39854014,
year = {2025},
author = {Sadda, SR},
title = {Photobiomodulation for Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {143},
number = {3},
pages = {195-196},
doi = {10.1001/jamaophthalmol.2025.0077},
pmid = {39854014},
issn = {2168-6173},
}
@article {pmid39853530,
year = {2025},
author = {Iyer, S and Lee, C and Amiji, MM},
title = {Biodegradable polymeric microsphere formulations of full-length anti-VEGF antibody bevacizumab for sustained intraocular delivery.},
journal = {Drug delivery and translational research},
volume = {15},
number = {9},
pages = {3149-3160},
pmid = {39853530},
issn = {2190-3948},
mesh = {*Bevacizumab/administration &amp; dosage/chemistry ; Microspheres ; *Angiogenesis Inhibitors/administration &amp; dosage/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Delayed-Action Preparations/chemistry/administration &amp; dosage ; Intravitreal Injections ; Polyesters/chemistry ; Humans ; Drug Liberation ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of central vision loss in the elderly population. Bevacizumab, a full-length humanized monoclonal anti-VEGF antibody, is commonly used off-label drug to treat AMD. However, the dosing regimen of bevacizumab and other anti-VEGF antibodies requires monthly intravitreal injections followed by regular intravitreal injections at 4-16-week intervals. In 2021, the FDA approved an innovative port delivery system of ranibizumab (Susvimo[®]) that can be implanted intravitreally to slowly release the active ingredient anti-VEGF antibody and reduce injection frequency to once every 6 months. An approach utilizing polymeric slow-release microspheres encapsulating a full-length antibody, such as bevacizumab, would be much more patient-friendly because it could be injected intravitreally, avoiding surgical implantation. While microsphere encapsulation is traditionally successful for small molecule hydrophobic drugs, we assessed two different polymers, namely poly(D, L-lactide-co-glycolide) (PLGA) and poly(epsilon-caprolactone) (PCL) and discovered the benefits of utilizing a slow degrading hydrophobic polymer such as PCL for large protein therapeutic. Using the traditional double emulsion fabrication method with PCL polymer, we could produce microspheres that encapsulate bevacizumab antibody and demonstrate the release of biologically active therapeutic agent for up to 60 days. This novel approach could lead to significant advancements in our field and potentially open new avenues for future research.},
}
@article {pmid39853518,
year = {2025},
author = {Talukdar, PD and Roy, H and Chatterji, U},
title = {Targeting breast cancer stem cells in ER-positive breast cancer by repurposing the benzoporphyrin derivative verteporfin as a YAP/TAZ small molecule inhibitor.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {154},
pmid = {39853518},
issn = {1573-4978},
support = {140(Sanc.)-BT/P/Budget/RD-75/2017//Department of Science and Technology and Biotechnology, GoWB, India/ ; },
mesh = {Humans ; *Verteporfin/pharmacology ; *Neoplastic Stem Cells/drug effects/metabolism ; *Breast Neoplasms/metabolism/drug therapy/pathology/genetics ; Female ; Drug Repositioning/methods ; *Transcription Factors/metabolism/antagonists &amp; inhibitors/genetics ; YAP-Signaling Proteins ; MCF-7 Cells ; Receptors, Estrogen/metabolism ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; Gene Expression Regulation, Neoplastic/drug effects ; Cell Line, Tumor ; Adaptor Proteins, Signal Transducing/metabolism/antagonists &amp; inhibitors ; },
abstract = {BACKGROUND: Current treatment strategies for hormone-dependent breast cancers, including adjuvant endocrine therapy, often fail due to persistence of breast cancer stem cells (brCSCs), which are significant contributors to tumor recurrence and treatment resistance. Therefore, gaining deeper insights into the molecular regulators driving breast cancer aggressiveness is important. Moreover, given the complexities and expenses involved in developing new pharmacological agents, the strategic repurposing of existing FDA-approved drugs to target these key molecular pathways presents a compelling approach for identifying novel therapeutic interventions aimed at mitigating tumor refractoriness.<br><br>METHODS: The study employs survival analysis from TCGA database, protein expression analyses alongside aldefluor assays, sphere formation efficiency tests to evaluate cellular stemness, and DCFDA analysis combined with antioxidant enzyme assays to investigate redox imbalance in brCSCs. These analyses were conducted following the genetic deletion of YAP/TAZ and pharmacological treatment with verteporfin.<br><br>RESULTS: The study demonstrated that transcriptional co-activators YAP/TAZ are significantly upregulated in chemotreated ER[+] patient breast tumors and MCF-7 mammospheres, where it was found to interact with the transcription factor SOX2 within the nuclear compartment. Genetic ablation and pharmacological inhibition of YAP/TAZ markedly impaired stemness properties and disrupted redox homeostasis in the mammospheres. Additionally, treatment with verteporfin led to a substantial reduction in the frequency and viability of brCSCs, suggesting their effective eradication.<br><br>CONCLUSION: This study highlights the potential of repurposing verteporfin, an FDA-approved drug originally formulated for age-related macular degeneration, as a therapeutic agent for targeting YAP/TAZ-mediated stemness and redox balance in brCSCs, thereby reducing their viability in ER-positive breast cancers.},
}
@article {pmid39850541,
year = {2025},
author = {Crass, RL and Prem, K and Gauderault, F and Ribeiro, R and Baumal, CR and Smith, B and Epling, D and Chapel, S},
title = {Population Pharmacokinetics of Pegcetacoplan in Patients with Geographic Atrophy or Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100657},
pmid = {39850541},
issn = {2666-9145},
abstract = {OBJECTIVE: To develop a population pharmacokinetic (PK) model to characterize serum pegcetacoplan concentration-time data after intravitreal administration in patients with geographic atrophy (GA) or neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Pharmacokinetic modeling.<br><br>PARTICIPANTS: Two hundred sixty-one patients with GA or nAMD enrolled in 4 clinical studies of pegcetacoplan.<br><br>METHODS: Serum concentration data were pooled from 4 clinical studies. Pegcetacoplan dosing included single intravitreal injections of 4, 10, and 20 mg and multiple intravitreal injections of 15 mg monthly or every other month. Considering a high proportion of samples were below the limit of quantification (BLQ) in serum following intravitreal administration, the M3 method of likelihood-based handling of data BLQ was employed in NONMEM (version 7.4). Covariate model development was performed using stepwise forward (&#x3b1;&#xa0;=&#xa0;0.05) and backward (&#x3b1;&#xa0;=&#xa0;0.001) selection. Predicted PK parameters and exposure metrics were generated via simulation in serum and vitreous humor.<br><br>MAIN OUTCOME MEASURES: Pharmacokinetic parameters.<br><br>RESULTS: Intravitreal pegcetacoplan displayed absorption-limited (i.e., "flip-flop") kinetics with median empirical Bayes estimated pegcetacoplan absorption and elimination half-lives of 13.1 days and 4.51 days, respectively. Vitreous exposure was predicted to be&#xa0;>1300-fold higher than serum exposure, with maximum concentrations in serum below the threshold required to elicit systemic pharmacodynamic effects. Drug accumulation from first dose to steady state was predicted to be minimal in serum (mean accumulation ratio&#xa0;=&#xa0;1.50 with monthly dosing, 1.10 with every-other-month dosing) and vitreous humor (mean accumulation ratio&#xa0;=&#xa0;1.30 with monthly dosing, 1.10 with every-other-month dosing). Age, sex, and baseline C3 level were identified as significant (P&#xa0;<&#xa0;0.001) predictors of apparent serum pegcetacoplan clearance after intravitreal administration; however, none of the covariate effects appeared to be clinically meaningful given the low absolute maximum serum concentrations achieved (<5 &#x3bc;g/mL). Concomitant anti-VEGF treatment did not significantly influence vitreous disposition of pegcetacoplan as assessed in a dedicated post hoc covariate model.<br><br>CONCLUSIONS: This population PK model adequately described the serum concentration-time profile of pegcetacoplan after intravitreal administration in adults with GA or nAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39849439,
year = {2025},
author = {Chakraborty, D and Sinha, TK and Mondal, S and Boral, S and Das, A and Majumbar, S and Mukherjee, A and Bhattacharya, R and Singh, SR},
title = {Innovator ranibizumab ComparEd to Biosimilar ranibizumab in combination with Expansile gas in submaculaR HemorrhaGe: the ICEBERG study.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {41},
pmid = {39849439},
issn = {1471-2415},
mesh = {Humans ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Male ; Female ; Intravitreal Injections ; Retrospective Studies ; *Biosimilar Pharmaceuticals/administration &amp; dosage/therapeutic use ; Visual Acuity ; Aged ; Tomography, Optical Coherence ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Retinal Hemorrhage/therapy/diagnosis/drug therapy/etiology ; *Fluorocarbons/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; *Endotamponade/methods ; *Wet Macular Degeneration/complications/drug therapy ; Fluorescein Angiography ; Treatment Outcome ; Follow-Up Studies ; Drug Therapy, Combination ; },
abstract = {PURPOSE: To compare the anatomical and visual outcomes in eyes with submacular hemorrhage (SMH) treated with a combination of ranibizumab (RBZ) either innovator or biosimilar (Razumab) and intravitreal perfluoropropane gas (C3F8).<br><br>METHODS: Treatment na&#xef;ve neovascular age related macular degeneration (n-AMD) patients with SMH were retrospectively analyzed. Patients received either innovator or biosimilar RBZ (3 loading doses followed by pro re nata regimen) and single injection of intravitreal C3F8. Optical coherence tomography (OCT) was performed at baseline, 1, 3 and 6 months. Changes in best corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 6 months. P value&#x2009;&#x2264;&#x2009;0.05 was considered statistically significant.<br><br>RESULTS: A total of 67 eyes (35 and 32 eyes in innovator and biosimilar group respectively) were analyzed. BCVA improved from 1.15&#x2009;&#xb1;&#x2009;0.19 to 0.51&#x2009;&#xb1;&#x2009;0.23 logarithm of minimum angle of resolution (logMAR) in innovator RBZ group (p&#x2009;<&#x2009;0.001) and from 1.17&#x2009;&#xb1;&#x2009;0.15 to 0.53&#x2009;&#xb1;&#x2009;0.20 logMAR in biosimilar RBZ group (p&#x2009;<&#x2009;0.001). Similarly, mean CMT showed significant reduction in both groups at 6 months (innovator RBZ: 609.5&#x2009;&#xb1;&#x2009;50.1&#xa0;&#x3bc;m to 254.3&#x2009;&#xb1;&#x2009;20.3&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.001; biosimilar RBZ: 602.3&#x2009;&#xb1;&#x2009;58.9&#xa0;&#x3bc;m to 251.8&#x2009;&#xb1;&#x2009;22.3&#xa0;&#x3bc;m, p&#x2009;<&#x2009;0.001). Intergroup comparisons between innovator and biosimilar RBZ showed no differences in either BCVA or CMT at all time points (all p values&#x2009;>&#x2009;0.05). Mean number of intravitreal injections was marginally higher in innovator group compared to biosimilar RBZ (4.37&#x2009;&#xb1;&#x2009;0.49 vs. 4.22&#x2009;&#xb1;&#x2009;0.42; p&#x2009;=&#x2009;0.18).<br><br>CONCLUSION: Biosimilar RBZ may act as a viable alternative to innovator RBZ to treat SMH with comparable anatomical and visual outcomes at 6 months.},
}
@article {pmid39849403,
year = {2025},
author = {Hashiya, N and Maruko, I and Miyaguchi, Y and Maruko, R and Hasegawa, T and Iida, T},
title = {Intraocular inflammation after intravitreal injection of aflibercept 8 mg for treatment-refractory neovascular age-related macular degeneration: a case report.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {42},
pmid = {39849403},
issn = {1471-2415},
mesh = {Humans ; Male ; *Recombinant Fusion Proteins/adverse effects/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Aged, 80 and over ; Intravitreal Injections/adverse effects ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Visual Acuity ; *Endophthalmitis/chemically induced/diagnosis ; },
abstract = {BACKGROUND: To report a case of intraocular inflammation (IOI) after intravitreal injection of aflibercept 8 mg for treatment-refractory neovascular age-related macular degeneration.<br><br>CASE PRESENTATION: An 80-year-old man with diabetes mellitus had neovascular age-related macular degeneration refractory to treatment with aflibercept 2&#xa0;mg. Despite ten injections of faricimab, the exudation remained, and we switched to brolucizumab, which resulted in a mild IOI. The IOI improved with only topical steroids, and we switched back to aflibercept 2&#xa0;mg for the exudation. However, the exudation remained, and we decided to switch to aflibercept 8&#xa0;mg after careful discussion with the patient. Two weeks later, he experienced minor ocular pain and photophobia. One month later, although a dry macula was achieved, severe visual impairment occurred due to anterior chamber inflammation, retinal vasculitis, and retinal vascular occlusion. We diagnosed the severe IOI following aflibercept 8&#xa0;mg and immediately started steroid eye drops and a sub-Tenon injection of triamcinolone acetonide. Although the inflammation resolved, his visual acuity did not improve.<br><br>CONCLUSIONS: This case demonstrated a potential dose-dependent inflammatory response following aflibercept 8&#xa0;mg, which did not occur with aflibercept 2&#xa0;mg in patients with a history of intraocular inflammation.},
}
@article {pmid39848699,
year = {2025},
author = {Martin-Pinardel, R and Izquierdo-Serra, J and Bernal-Morales, C and De Zanet, S and Garay-Aramburu, G and Puzo, M and Arruabarrena, C and Sararols, L and Abraldes, M and Broc, L and Escobar-Barranco, JJ and Figueroa, M and Zapata, MA and Ruiz-Moreno, JM and Parrado-Carrillo, A and Moll-Udina, A and Alforja, S and Figueras-Roca, M and Gómez-Baldó, L and Ciller, C and Apostolopoulos, S and Mishchuk, A and Casaroli-Marano, RP and Zarranz-Ventura, J and , },
title = {Fluid fluctuations assessed with artificial intelligence during the maintenance phase impact anti-vascular endothelial growth factor visual outcomes in a multicentre, routine clinical care national age-related macular degeneration database.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {10},
pages = {1161-1170},
doi = {10.1136/bjo-2024-325615},
pmid = {39848699},
issn = {1468-2079},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Female ; Male ; Aged ; *Subretinal Fluid/diagnostic imaging ; Intravitreal Injections ; *Artificial Intelligence ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Databases, Factual ; Follow-Up Studies ; Fluorescein Angiography ; },
abstract = {AIM: To evaluate the impact of fluid volume fluctuations quantified with artificial intelligence in optical coherence tomography scans during the maintenance phase and visual outcomes at 12 and 24 months in a real-world, multicentre, national cohort of treatment-naïve neovascular age-related macular degeneration (nAMD) eyes.<br><br>METHODS: Demographics, visual acuity (VA) and number of injections were collected using the Fight Retinal Blindness tool. Intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), total fluid (TF) and central subfield thickness (CST) were quantified using the RetinAI Discovery tool. Fluctuations were defined as the SD of within-eye quantified values, and eyes were distributed according to SD quartiles for each biomarker.<br><br>RESULTS: A total of 452 na&#xef;ve nAMD eyes were included. Eyes with highest (Q4) versus lowest (Q1) fluid fluctuations showed significantly worse VA change (months 3-12) in IRF -3.91 versus 3.50 letters, PED -4.66 versus 3.29, TF -2.07 versus 2.97 and CST -1.85 versus 2.96 (all p<0.05), but not for SRF 0.66 versus 0.93 (p=0.91). Similar VA outcomes were observed at month 24 for PED -8.41 versus 4.98 (p<0.05), TF -7.38 versus 1.89 (p=0.07) and CST -10.58 versus 3.60 (p<0.05). The median number of injections (months 3-24) was significantly higher in Q4 versus Q1 eyes in IRF 9 versus 8, SRF 10 versus 8 and TF 10 versus 8 (all p<0.05).<br><br>CONCLUSION: This multicentre study reports a negative effect in VA outcomes of fluid volume fluctuations during the maintenance phase in specific fluid compartments, suggesting that anatomical and functional treatment response patterns may be fluid-specific.},
}
@article {pmid39848558,
year = {2025},
author = {Campagno, KE and Lu, W and Sripinun, P and Albalawi, F and Cenaj, A and Mitchell, CH},
title = {Priming and release of cytokine IL-1β in microglial cells from the retina.},
journal = {Experimental eye research},
volume = {252},
number = {},
pages = {110246},
pmid = {39848558},
issn = {1096-0007},
support = {T32 EY007035/EY/NEI NIH HHS/United States ; R01 EY015537/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; TL1 TR001880/TR/NCATS NIH HHS/United States ; R01 EY013434/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Microglia/metabolism/drug effects ; *Interleukin-1beta/metabolism/genetics ; Mice ; Receptors, Purinergic P2X7/metabolism ; Rats ; Adenosine Triphosphate/pharmacology/analogs &amp; derivatives ; *Retina/metabolism/cytology ; Mice, Inbred C57BL ; RNA, Messenger/genetics/metabolism ; Cells, Cultured ; Rats, Sprague-Dawley ; Blotting, Western ; Mice, Transgenic ; Purinergic P2X Receptor Antagonists/pharmacology ; },
abstract = {The P2X7 receptor (P2X7R) for extracellular ATP is implicated in several forms of retinal degeneration, including diabetic retinopathy, age-related macular degeneration, and glaucoma. P2X7R stimulation can trigger release of master cytokine IL-1β from microglia in the brain and from macrophages, but evidence of release from retinal microglia is indirect. Isolated mouse and rat retinal microglia, and wholemounts from Cx3CR1[+/GFP] mice, were examined to determine if ATP induced IL-1β release directly from retinal microglial cells and if it also primed expression of IL-1β on an mRNA and protein level. Isolated retinal microglia were ramified and expressed low levels of polarization markers unless provoked. Over 90% of isolated microglial cells expressed P2X7R, with cytoplasmic Ca[2+] elevation following receptor stimulation. ATP induced a dose-dependent release of IL-1β from primed microglial cells that was blocked by P2X7R antagonist A839977 and emulated by agonist BzATP. P2X7R stimulation also primed Il1b mRNA in isolated microglia cells. BzATP increased IL-1β immunostaining and GFP fluorescence throughout lamina of retinal wholemounts from CX3CR1[+/GFP] mice. Some of the IL-1β and GFP signals colocalized, particularly in the outer retina, and in projections extending distally through photoreceptor layers. The inner retina had more microglia without IL-1β, and more IL-1β staining without microglia. Substantial IL-1β release was also detected from rat retinal microglial cells, but not optic nerve head astrocytes. In summary, this study implicates microglial cells as a key source of released IL-1β when levels of extracellular ATP are increased following retinal damage, and suggest a greater participation in the outer retina.},
}
@article {pmid39848020,
year = {2025},
author = {Wang, SW and Li, P and Liu, SY and Huang, DL and Zhang, SJ and Zeng, XX and Lan, T and Mao, KL and Gao, Y and Cheng, YF and Shen, Q and Ruan, YP and Mao, ZJ},
title = {Astragaloside IV inhibits retinal pigment epithelial cell senescence and reduces IL-1β mRNA stability by targeting FTO-mediated m[6]A methylation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {138},
number = {},
pages = {156408},
doi = {10.1016/j.phymed.2025.156408},
pmid = {39848020},
issn = {1618-095X},
mesh = {Animals ; *Triterpenes/pharmacology ; *Saponins/pharmacology ; *Retinal Pigment Epithelium/drug effects/cytology ; *Interleukin-1beta/metabolism/genetics ; Mice ; *Cellular Senescence/drug effects ; Humans ; Cell Line ; *Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism ; *Macular Degeneration/drug therapy ; *RNA Stability/drug effects ; Methylation/drug effects ; Mice, Inbred C57BL ; Adenosine/analogs &amp; derivatives/metabolism ; Male ; Iodates ; Disease Models, Animal ; },
abstract = {BACKGROUND: Resistance to senescence in retinal pigment epithelial (RPE) cells can delay the progression of age-related macular degeneration (AMD). However, the mechanisms underlying RPE cell senescence remain inadequately understood, and effective therapeutic strategies are lacking. While astragaloside IV (Ast) has demonstrated anti-aging properties, its specific effects on RPE cell senescence and potential mechanisms are not yet fully clarified.<br><br>PURPOSE: This study aimed to explore the impacts of Ast on RPE cell senescence and to uncover the molecular mechanisms involved.<br><br>METHODS: The therapeutic efficacy of Ast was assessed using sodium iodate (NaIO3)-induced adult retinal pigment epithelial cell line 19 (ARPE-19) cell models and an AMD mouse model. To investigate the mechanisms by which Ast mitigated RPE cell senescence, RNA sequencing (RNA-seq), drug affinity responsive target stability-mass spectrometry (DARTS-MS), cellular thermal shift assay (CETSA), reverse transcription quantitative PCR (RT-qPCR), as well as western blotting were conducted.<br><br>RESULTS: Ast significantly inhibited NaIO3-treated ARPE-19 cell senescence and protected against NaIO3-induced AMD in mice. RNA-seq analysis revealed that Ast significantly attenuated inflammation-related signaling pathways and reduced the mRNA levels of interleukin-1 beta (IL-1&#x3b2;). Specifically, Ast decreased the stability of IL-1&#x3b2; mRNA while enhancing its N6-methyladenosine (m[6]A) methylation. Furthermore, Ast directly interacted with fat mass and obesity-associated protein (FTO). Knockdown or pharmacological inhibition of FTO mitigated the senescence and IL-1&#x3b2; expression in NaIO3-treated ARPE-19 cells. FTO was essential for Ast to inhibit cellular senescence and IL-1&#x3b2; expression. Additionally, inhibition or knockdown of FTO conferred also provided resistance to AMD in the murine model.<br><br>CONCLUSION: Our results indicated that Ast significantly attenuated RPE cell senescence and showed anti-AMD properties. FTO was demonstrated to be a promising therapeutic target for AMD treatment. These findings may provide a deeper understanding of the molecular mechanisms underlying RPE cell senescence in AMD and offer potential strategies for its prevention and management.},
}
@article {pmid39847370,
year = {2025},
author = {Bruening, W and Kim, S and Yeh, S and Rishi, P and Conrady, CD},
title = {Inflammation and Occlusive Retinal Vasculitis Post Faricimab.},
journal = {JAMA ophthalmology},
volume = {143},
number = {3},
pages = {232-235},
pmid = {39847370},
issn = {2168-6173},
mesh = {Humans ; *Retinal Vasculitis/chemically induced/diagnosis ; Retrospective Studies ; Male ; Female ; Aged ; Intravitreal Injections ; *Angiogenesis Inhibitors/adverse effects ; Visual Acuity ; Fluorescein Angiography ; Tomography, Optical Coherence ; Middle Aged ; *Recombinant Fusion Proteins/adverse effects ; Macular Edema/drug therapy ; Antibodies, Bispecific ; },
abstract = {IMPORTANCE: Randomized clinical trials have shown the safety and efficacy of faricimab as a novel vascular endothelial growth factor and angiopoietin-2 inhibitor in the treatment of neovascular age-related macular degeneration (nAMD) and macular edema of various etiologies. However, more rare adverse events may not be considered in clinical trials.<br><br>OBJECTIVE: To describe 3 eyes that developed irreversible vision loss following initial mild intraocular inflammation (IOI) to faricimab.<br><br>This retrospective case series from a single academic tertiary referral center (University of Nebraska Medical Center) from October 2023 to August 2024 included 3 patients who developed occlusive retinal vasculitis (ORV) following an initial sensitization with intravitreal faricimab. Two eyes were being treated with faricimab for nAMD, and the other 2 eyes were treated for diabetic macular edema.<br><br>INTERVENTION: Patients exposed to faricimab after the prior development of mild IOI.<br><br>MAIN OUTCOMES AND MEASURES: Clinical symptoms, signs, and clinical course of patients who were diagnosed with ORV following rechallenge with faricimab.<br><br>RESULTS: Mild IOI developed in 4 eyes following faricimab, and ORV developed in 3 eyes with repeated challenge. This resulted in profound, irreversible vision loss, despite treatment with topical and systemic steroids. In the eye that did not develop ORV following rechallenge, there have been no repeated adverse events despite restarting intravitreal faricimab injections.<br><br>CONCLUSIONS AND RELEVANCE: Given these observations with repeated challenge, caution is advisable when using the same biologic after the development of even mild IOI with prior injection. It appears an immunological memory response is elicited with these repeated exposures, resulting in the development of ORV.},
}
@article {pmid39847181,
year = {2025},
author = {Hoshino, J and Matsumoto, H and Nakamura, K and Akiyama, H},
title = {Efficacy of switching to brolucizumab for neovascular age-related macular degeneration refractory to faricimab.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {2},
pages = {221-229},
pmid = {39847181},
issn = {1613-2246},
mesh = {Humans ; Retrospective Studies ; Female ; Intravitreal Injections ; Male ; *Visual Acuity ; Tomography, Optical Coherence ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Fluorescein Angiography ; Treatment Outcome ; *Drug Substitution ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Follow-Up Studies ; Aged, 80 and over ; Fundus Oculi ; Macula Lutea/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To evaluate the treatment outcomes of switching to intravitreal brolucizumab (IVBr) for neovascular age-related macular degeneration (nAMD) which did not achieve a dry macula even with 4- or 8-week intervals of intravitreal faricimab (IVF).<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively studied 33 eyes of 33 consecutive patients with nAMD who switched to IVBr from IVF, assessing best corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), and exudative status at baseline and after the switch. For patients that switched 4 weeks after the last IVF (4-week interval group), treatment outcomes were evaluated 4 weeks after the switch. For patients that switched 8 weeks after the last IVF (8-week interval group), treatment outcomes were evaluated after the first 8-week interval following the switch.<br><br>RESULTS: Thirty-one eyes had completed IVBr treatment up to the evaluation point after the switch. There were no significant changes in BCVA at baseline and after the switch in either group. FT and CCT significantly decreased after the switch compared with baseline in both groups. Moreover, in both groups, exudative changes disappeared or decreased in most cases after the switch. The dry macula rate after the switch was 37.5% and 34.8% in the 4-week and 8-week interval group, respectively. Although brolucizumab-related intraocular inflammation was observed in 3 eyes (9.1%) after the switch, it was ameliorated in response to steroid therapy.<br><br>CONCLUSION: Switching to IVBr for nAMD refractory to IVF was generally effective in improving exudative changes in the short term.},
}
@article {pmid39844926,
year = {2025},
author = {Qarawani, A and Naaman, E and Ben-Zvi Elimelech, R and Harel, M and Sigal-Dror, S and Ben-Zur, T and Ziv, T and Offen, D and Zayit-Soudry, S},
title = {Mesenchymal stem cell-derived exosomes mitigate amyloid β-induced retinal toxicity: Insights from rat model and cellular studies.},
journal = {Journal of extracellular biology},
volume = {4},
number = {1},
pages = {e70024},
pmid = {39844926},
issn = {2768-2811},
abstract = {Amyloid β (Aβ) has emerged as a pathophysiological driver in age-related macular degeneration (AMD), emphasizing its significance in the aetiology of this prevalent sight-threatening condition. The multifaceted nature of AMD pathophysiology, presumably involving diverse retinal cascades, corresponds with the complexity of Aβ-induced retinopathy. Therefore, targeting a broad array of pathogenic processes holds promise for therapeutic intervention in AMD-associated retinal pathology. This study investigates the potential of exosomes derived from adipose tissue mesenchymal stem cells (AT-MSC-Exosomes) in alleviating Aβ-induced retinotoxicity. Through intravitreal injections in wild-type rats and RPE-like cell culture experiments, we examined the protective effects of AT-MSC-Exosomes against Aβ42 retinotoxicity. Our findings reveal that pre-treatment with AT-MSC-Exosomes enabled nearly-intact retinal function in vivo and maintained retinal cell viability in vitro, evidenced by longitudinal electroretinography (ERG) and XTT proliferation assays, respectively. Fluorescent labelling demonstrated increased migration of AT-MSC-Exosomes towards retinal cells under conditions of amyloid-related toxicity. Proteomic analysis indicated a decrease in the retinal levels of heat-shock proteins activated by pathogenic Aβ fibrils following AT-MSC-Exosome treatment. Similarly, immunostaining highlighted the modulation of α-crystallin expression in retinal astrocytes by AT-MSC-Exosomes. These results suggest the potential therapeutic relevance of AT-MSC-Exosomes in Aβ-related retinal pathology, offering a promising avenue for future AMD treatment strategies.},
}
@article {pmid39843622,
year = {2025},
author = {Gholami, S and Jannat, FE and Thompson, AC and Ong, SSY and Lim, JI and Leng, T and Tabkhivayghan, H and Alam, MN},
title = {Distributed training of foundation models for ophthalmic diagnosis.},
journal = {Communications engineering},
volume = {4},
number = {1},
pages = {6},
pmid = {39843622},
issn = {2731-3395},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; P30EY026877//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R21 EY035271/EY/NEI NIH HHS/United States ; R21EY035271//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R15 EY035804/EY/NEI NIH HHS/United States ; P30 DK124723/DK/NIDDK NIH HHS/United States ; Faculty Research Grant//UNC | University of North Carolina at Charlotte (UNC Charlotte)/ ; },
abstract = {Vision impairment affects nearly 2.2 billion people globally, and nearly half of these cases could be prevented with early diagnosis and intervention-underscoring the urgent need for reliable and scalable detection methods for conditions like diabetic retinopathy and age-related macular degeneration. Here we propose a distributed deep learning framework that integrates self-supervised and domain-adaptive federated learning to enhance the detection of eye diseases from optical coherence tomography images. We employed a self-supervised, mask-based pre-training strategy to develop a robust foundation encoder. This encoder was trained on seven optical coherence tomography datasets, and we compared its performance under local, centralized, and federated learning settings. Our results show that self-supervised methods-both centralized and federated-improved the area under the curve by at least 10% compared to local models. Additionally, incorporating domain adaptation into the federated learning framework further boosted performance and generalization across different populations and imaging conditions. This approach supports collaborative model development without data sharing, providing a scalable, privacy-preserving solution for effective retinal disease screening and diagnosis in diverse clinical settings.},
}
@article {pmid39842718,
year = {2025},
author = {Berni, A and Coletto, A and Li, J and Shen, M and Bandello, F and Reibaldi, M and Borrelli, E},
title = {Macular Atrophy in Neovascular Age-related Macular Degeneration: A Systematic Review and Meta-analysis.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {7},
pages = {625-644},
doi = {10.1016/j.oret.2025.01.011},
pmid = {39842718},
issn = {2468-6530},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy/complications/diagnosis ; Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Fluorescein Angiography/methods ; *Macula Lutea/pathology ; Tomography, Optical Coherence/methods ; Intravitreal Injections ; Incidence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Atrophy ; Visual Acuity ; Fundus Oculi ; },
abstract = {TOPIC: Macular atrophy incidence in neovascular age-related macular degeneration (AMD) patients undergoing anti-VEGF treatment.<br><br>CLINICAL RELEVANCE: Macular atrophy is a significant event that may occur in eyes with neovascular AMD treated with anti-VEGF therapy.<br><br>METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO, CRD42024474924). A comprehensive literature search of MEDLINE, EMBASE, and Web of Science was performed up to November 1, 2023. Randomized and nonrandomized studies of treatment-naive neovascular AMD patients reporting macular atrophy incidence at 24 &#xb1; 3 months after anti-VEGF therapy were eligible. Two independent reviewers conducted screening, data extraction, and quality assessment. For randomized controlled trials, the Cochrane Risk of Bias 2 tool was employed, whereas nonrandomized studies were evaluated using the Risk Of Bias In Nonrandomized Studies of Interventions tool. Random-effects meta-analysis models accounted for study variability. Heterogeneity was assessed with the I[2] statistic, and publication bias by funnel plots and Egger test. The primary outcome was the incidence of new macular atrophy at 24 months post-treatment, with secondary outcomes at 12 months. Atrophy was diagnosed using color fundus photograph, fluorescein angiography, fundus autofluorescence, OCT, or multimodal imaging.<br><br>RESULTS: Twenty-three studies met the inclusion criteria for qualitative analysis, with 11 included in the meta-analysis (N = 3013 eyes). The pooled 24-month incidence of macular atrophy was 29% (95% confidence interval [CI]: 20%-38%, I[2] = 93%). Subgroup analysis revealed incidence rates of 26% (95% CI: 15%-37%, I[2] = 88%) for 814 eyes with type 1/2 macular neovascularization (MNV), 49% (95% CI: 18%-80%, I[2] = 92%) for type 3 MNV (N = 230 eyes), and 29% (95% CI: 18%-40%, I[2] = 96%) for all MNV types (N = 2131 eyes). The pooled 12-month incidence among 2214 eyes was 11% (95% CI: 4%-18%, I[2] = 93%). The certainty of evidence, as assessed by Grading of Recommendations, Assessment, Development and Evaluation, was low.<br><br>CONCLUSION: Although this meta-analysis has limitations, including a moderate risk of bias in nonrandomized studies, inconsistencies in the results indicated by high heterogeneity, and imprecision due to the different imaging modalities used to diagnose macular atrophy, our results suggest that macular atrophy could be a common complication in patients with neovascular AMD receiving anti-VEGF therapy.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39842717,
year = {2025},
author = {Yap, DWT and Tan, BKJ and Chong, KTY and Wong, TY and Cheung, CMG},
title = {Persistence of Retinal Fluid after Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {7},
pages = {603-617},
doi = {10.1016/j.oret.2025.01.010},
pmid = {39842717},
issn = {2468-6530},
mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Subretinal Fluid ; *Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; *Ranibizumab/administration &amp; dosage ; },
abstract = {TOPIC: To evaluate the prognosis of retinal fluid resolution in neovascular age-related macular degeneration (nAMD) after initiating treatment in terms of the prevalence of eyes with retinal fluid, the proportion of eyes which never achieve a fluid-free retina throughout the course of treatment, and the relationship between retinal fluid and visual acuity outcome.<br><br>CLINICAL RELEVANCE: Retinal fluid often persists or recurs after initiating treatment for nAMD. It is unclear what proportion never achieve fluid resolution throughout their treatment course.<br><br>METHODS: MEDLINE, Embase, and Web of Science were searched till May 2024 for randomized control trials (including post hoc analyses) and prospective studies treating nAMD patients with intravitreal anti-VEGF injections (CRD42023437516). To investigate the prevalence of persistent fluid, a meta-analysis of proportions was conducted at key time points. To estimate the proportion of poor-responding patients, iterative algorithms were used to simulate individual patient data from time-to-fluid-resolution Kaplan-Meier curves. Cure fractions from Weibull nonmixture cure models were meta-analyzed. Finally, the weighted mean best-corrected visual acuity (BCVA) difference (WMD) between patients with and without any fluid, subretinal fluid (SRF), or intraretinal fluid (IRF) was calculated.<br><br>RESULTS: Fifty articles were included across the meta-analyzed outcomes. The pooled prevalence of retinal fluid was 41.4% (95% confidence interval [CI], 35.0%-48.0%) at 1 year, and 47.4% (95% CI, 38.5%-56.5%) at 2 years. The pooled median time to first fluid resolution was 10.2 weeks (95% CI, 7.66-14.59 weeks). Cure modeling suggests that 17.6% (95% CI, 11.9%-25.3%) of patients may never achieve a fluid-free finding in the long run despite prolonged treatment. Eyes with SRF had significantly higher BCVA compared with eyes without SRF at 12 months (WMD, 2.39 letters; 95% CI, 0.27-4.52; P < 0.05). Eyes with IRF had significantly poorer BCVA compared to eyes without IRF at 12 months (WMD, -5.38 letters; 95% CI, -8.65 to -2.11; P < 0.05). At long follow-up (>60 months), eyes with SRF had significantly higher BCVA compared to eyes without SRF (WMD, 7.69 letters; 95% CI, 2.79-12.59; P < 0.05).<br><br>CONCLUSION: Notwithstanding the heterogeneity in studies included, our analysis estimates that nearly half of all treated patients have persistent retinal fluid after initiating treatment and a substantial 18% of patients may never attain complete fluid resolution. We confirm that SRF is associated with better visual outcomes, whereas IRF is associated with worse visual outcomes.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39842469,
year = {2025},
author = {Sarkar, T and Gogoi, NR and Jana, BK and Mazumder, B},
title = {Formulation Advances in Posterior Segment Ocular Drug Delivery.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {41},
number = {3},
pages = {101-130},
doi = {10.1089/jop.2024.0153},
pmid = {39842469},
issn = {1557-7732},
mesh = {Humans ; *Drug Delivery Systems/methods ; *Posterior Eye Segment/metabolism/drug effects ; Animals ; Administration, Ophthalmic ; *Eye Diseases/drug therapy ; Blood-Retinal Barrier/metabolism ; Nanoparticles ; },
abstract = {Posterior segment ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion, are leading causes of vision impairment and blindness worldwide. Effective management of these conditions remains a formidable challenge due to the unique anatomical and physiological barriers of the eye, including the blood-retinal barrier and rapid drug clearance mechanisms. To address these hurdles, nanostructured drug delivery systems are proposed to overcome ocular barriers, target the retina, and enhance permeation while ensuring controlled release. Traditional therapeutic approaches, such as intravitreal injections, pose significant drawbacks, including patient discomfort, poor compliance, and potential complications. Therefore, understanding the physiology and clearance mechanism of eye could aid in the design of novel formulations that could be noninvasive and deliver drugs to reach the target site is pivotal for effective treatment strategies. This review focuses on recent advances in formulation strategies for posterior segment ocular drug delivery, highlighting their potential to overcome these limitations. Furthermore, the potential of nanocarrier systems such as in-situ gel, niosomes, hydrogels, dendrimers, liposomes, nanoparticles, and nanoemulsions for drug delivery more effectively and selectively is explored, and supplemented with illustrative examples, figures, and tables. This review aims to provide insights into the current state of posterior segment drug delivery, emphasizing the need for interdisciplinary approaches to develop patient-centric, minimally invasive, and effective therapeutic solutions.},
}
@article {pmid39841909,
year = {2025},
author = {Berzack, S and Parekh, PK},
title = {Drusen Regression Following Macular Hole Surgery: A Case Report.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001720},
pmid = {39841909},
issn = {1937-1578},
abstract = {PURPOSE: To report a case of drusen regression following pars plana vitrectomy with internal limiting membrane peel (ILMP) in a patient with a full-thickness macular hole and dry age-related macular degeneration (AMD).<br><br>METHODS: A 67-year-old gentleman presented in April 2024 with a full-thickness macular hole in OS and intermediate dry AMD OU. The patient underwent pars plana vitrectomy, ILMP, and an injection of sulfur hexafluoride gas for macular hole repair in OS. The patient's macular changes were monitored through visual acuity, fundus examination and optical coherence tomography (OCT) imaging at baseline and follow-up visits.<br><br>RESULTS: The macular hole was closed and there was early stability of the macular drusen in OU. At a five-month follow-up in September 2024, he reported improved vision from 20/100 baseline to 20/40. Fundus examination as well as OCT imaging demonstrated a significant reduction of macular drusen in the operated eye, which was not observed in the fellow eye.<br><br>CONCLUSION: This case demonstrates successful surgical management of a full-thickness macular hole in a patient with concomitant drusen regression. The regression of drusen was limited to the operated eye, which suggests that surgical interventions may influence the course of AMD in certain patients.},
}
@article {pmid39841905,
year = {2025},
author = {Lee, H and Kim, N and Kim, NH and Chung, H and Kim, HC},
title = {GENERATIVE DEEP LEARNING APPROACH TO PREDICT POSTTREATMENT OPTICAL COHERENCE TOMOGRAPHY IMAGES OF AGE-RELATED MACULAR DEGENERATION AFTER 12 MONTHS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {6},
pages = {1184-1191},
doi = {10.1097/IAE.0000000000004409},
pmid = {39841905},
issn = {1539-2864},
support = {RS-2024-00453840//National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Deep Learning ; Female ; Male ; Fluorescein Angiography/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Visual Acuity ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Follow-Up Studies ; Aged, 80 and over ; Retrospective Studies ; Ranibizumab/administration &amp; dosage ; *Macula Lutea/pathology/diagnostic imaging ; Time Factors ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: Predicting long-term anatomical responses in neovascular age-related macular degeneration patients is critical for patient-specific management. This study validates a generative deep learning model to predict 12-month posttreatment optical coherence tomography (OCT) images and evaluates the impact of incorporating clinical data on predictive performance.<br><br>METHODS: A total of 533 eyes from 513 treatment-na&#xef;ve neovascular age-related macular degeneration patients were analyzed. A conditional generative adversarial network served as the baseline model, generating 12-month OCT images using pretreatment OCT, fluorescein angiography, and indocyanine green angiography. We then sequentially added OCT after three loading doses, baseline visual acuity, treatment regimen (pro re nata or treat-and-extend), drug type, and switching events. The generated and patient OCT images were compared for intraretinal fluid, subretinal fluid, pigment epithelial detachment, and subretinal hyperreflective material, both qualitatively and quantitatively.<br><br>RESULTS: The baseline model achieved acceptable accuracy for 4 macular fluid compartments (range 0.74-0.96). Incorporating OCT after loading doses and other clinical parameters improved accuracy (range 0.91-0.98). With all the clinical inputs, the model achieved 92% accuracy in distinguishing wet macular status from dry macular status. The segmented fluid compartments in the generated images correlated positively with those in the patient images.<br><br>CONCLUSION: Integrating clinical and treatment data, particularly OCT data after loading doses, significantly enhanced the 12-month predictive performance of conditional generative adversarial networks. This approach can help clinicians anticipate anatomical outcomes and guide personalized, long-term neovascular age-related macular degeneration treatment strategies.},
}
@article {pmid39840952,
year = {2025},
author = {Momenaei, B and Yonekawa, Y and Abril, P and McCullough, R and Abbey, AM},
title = {Outcomes of Intravitreal Aflibercept 8 mg in Eyes With Neovascular Age-Related Macular Degeneration Previously Treated With Faricimab.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {4},
pages = {206-211},
doi = {10.3928/23258160-20241205-01},
pmid = {39840952},
issn = {2325-8179},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Retrospective Studies ; Female ; Male ; Visual Acuity/physiology ; Tomography, Optical Coherence ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged, 80 and over ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Middle Aged ; Follow-Up Studies ; Antibodies, Bispecific ; },
abstract = {BACKGROUND AND OBJECTIVE: To assess the efficacy of intravitreal aflibercept 8 mg in treating neovascular age-related macular degeneration (nAMD) in patients previously treated with faricimab.<br><br>PATIENTS AND METHODS: A retrospective study was conducted on nAMD patients with suboptimal response to faricimab injections who were switched to intravitreal aflibercept 8 mg. Visual acuity (VA) and optical coherence tomography features were evaluated.<br><br>RESULTS: The study included 135 eyes from 85 patients who received an average of 7.4 (4) faricimab injections with a mean interval of 53 days, which decreased to 48 days by the 5th aflibercept 8 mg injection (P = 0.056). Mean VA at the time of switch was 63.9 (14.4) letters and was 65 (13.5) letters after four aflibercept 8 mg injections (P = 0.726). Mean central foveal thickness (CFT) at switch was 325 (104) &#xb5;m which decreased to 272 (65) after four aflibercept 8 mg injections (P < 0.001). The incidence of intraretinal fluid and subretinal hemorrhage increased from 31.3% and 8.1% at switch to 52.2% and 21.7% (P = 0.029 and 0.004), respectively.<br><br>CONCLUSIONS: Switching from faricimab to aflibercept 8 mg did not result in interval extension or VA improvement. CFT decreased, but intraretinal fluid and subretinal hemorrhage increased. Further studies are warranted. [Ophthalmic Surg Lasers Imaging Retina 2025;56:206-211.].},
}
@article {pmid39840199,
year = {2024},
author = {Banoub, RG and Sanghvi, H and Gill, GS and Paredes, AA and Bains, HK and Patel, A and Agarwal, A and Gupta, S},
title = {Enhancing Ophthalmic Care: The Transformative Potential of Digital Twins in Healthcare.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e76209},
pmid = {39840199},
issn = {2168-8184},
abstract = {This literature review explores the emerging role of digital twin (DT) technology in ophthalmology, emphasizing its potential to revolutionize personalized medicine. DTs integrate diverse data sources, including genetic, environmental, and real-time patient data, to create dynamic, predictive models that enhance risk assessment, surgical planning, and postoperative care. The review highlights vital case studies demonstrating the application of DTs in improving the early detection and management of diseases such as glaucoma and age-related macular degeneration. While implementing DTs presents challenges, including data integration and privacy concerns, the potential benefits, such as improved patient outcomes and cost savings, position DTs as a valuable tool in the future of ophthalmic care. The review underscores the need for further research to address these challenges and fully realize the potential of DTs in clinical practice.},
}
@article {pmid39839515,
year = {2025},
author = {Toro, MD and Savastano, A and Aroca, FV and Sasso, P and Francione, G and Fioretto, G and Montemagni, M and Xompero, C and D'Onofrio, NC and Costagliola, C and Rizzo, S},
title = {Smaller-incision new-generation implantable miniature telescope in late-stage age-related macular degeneration: 6 month outcomes.},
journal = {Heliyon},
volume = {11},
number = {1},
pages = {e41116},
pmid = {39839515},
issn = {2405-8440},
abstract = {PURPOSE: To evaluate the intermediate-term visual and safety outcomes of the small-incision second-generation implantable miniature telescope (SING IMT) in patients with late-stage age-related macular degeneration (AMD) at 6 months post-surgery.<br><br>DESIGN: Retrospective cohort study.<br><br>METHODS: Medical records of patients implanted with the SING IMT at two sites in Italy were reviewed. Outcomes evaluated up to 6 months post-surgery included best-corrected distance (BCDVA) and distance-corrected near (DCNVA) visual acuity, intraocular pressure (IOP), anterior chamber depth (ACD), corneal endothelial cell density (ECD), and adverse events.<br><br>RESULTS: The study involved 35 patients (mean age: 77.4 years). At 6 months post-surgery, the mean&#xa0;&#xb1;&#xa0;standard deviation (SD) change in BCDVA from baseline was -0.29&#xa0;&#xb1;&#xa0;0.142, and at least 1-, 2-, and 3-line gains in BCDVA were achieved in 97.1&#xa0;%, 68.6&#xa0;% and 51.4&#xa0;%, of operated eyes, respectively. The percentage of patients able to read at near distance increased from 28.6&#xa0;% at baseline to 97.1&#xa0;% at 6 months post-surgery with a mean improvement of -0.57&#xa0;&#xb1;&#xa0;0.206. No clinically meaningful change from baseline was observed in terms of IOP or ACD. The mean (SD) change from baseline in ECD at 6 months in operated eyes was -280.7 (315.9) cells/mm[2] (-11.4&#xa0;%). The most frequent adverse event was corneal edema, and all cases were resolved with topical medications.<br><br>CONCLUSIONS: This intermediate-term assessment confirms that SING IMT implantation improved distance and near vision, with a low impact on the corneal endothelium and an acceptable and manageable rate of complications and adverse effects.},
}
@article {pmid39839014,
year = {2025},
author = {Yang, Z and Tian, D and Zhao, X and Zhang, L and Xu, Y and Lu, X and Chen, Y},
title = {Evolutionary patterns and research frontiers of artificial intelligence in age-related macular degeneration: a bibliometric analysis.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {1},
pages = {813-830},
pmid = {39839014},
issn = {2223-4292},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) represents a significant clinical concern, particularly in aging populations, and recent advancements in artificial intelligence (AI) have catalyzed substantial research interest in this domain. Despite the growing body of literature, there remains a need for a comprehensive, quantitative analysis to delineate key trends and emerging areas in the field of AI applications in AMD. This bibliometric analysis sought to systematically evaluate the landscape of AI-focused research on AMD to illuminate publication patterns, influential contributors, and focal research trends.<br><br>METHODS: Using the Web of Science Core Collection (WoSCC), a search was conducted to retrieve relevant publications from 1992 to 2023. This analysis involved an array of bibliometric indicators to map the evolution of AI research in AMD, assessing parameters such as publication volume, national/regional and institutional contributions, journal impact, author influence, and emerging research hotspots. Visualization tools, including Bibliometrix, CiteSpace and VOSviewer, were employed to generate comprehensive assessments of the data.<br><br>RESULTS: A total of 1,721 publications were identified, with the USA leading in publication output and the University of Melbourne as the most prolific institution. The journal Investigative Ophthalmology &amp; Visual Science published the highest number of articles, and Schmidt-Eerfurth emerged as the most active author. Keyword and clustering analyses, along with citation burst detection, revealed three distinct research stages within the field from 1992 to 2023. Presently, research efforts are concentrated on developing deep learning (DL) models for AMD diagnosis and progression prediction. Prominent emerging themes include early detection, risk stratification, and treatment efficacy prediction. The integration of large language models (LLMs) and vision-language models (VLMs) for enhanced image processing also represents a novel research frontier.<br><br>CONCLUSIONS: This bibliometric analysis provides a structured overview of prevailing research trends and emerging directions in AI applications for AMD. These findings furnish valuable insights to guide future research and foster collaborative advancements in this evolving field.},
}
@article {pmid39838458,
year = {2025},
author = {Chen, Y and Jin, E and Abdouh, M and Bonneil, &#xc9; and Jimenez Cruz, DA and Tsering, T and Zhou, Q and Fuentes-Rodriguez, A and Bartolomucci, A and Goyeneche, A and Landreville, S and Burnier, MN and Burnier, JV},
title = {Co-isolation of human donor eye cells and development of oncogene-mutated melanocytes to study uveal melanoma.},
journal = {BMC biology},
volume = {23},
number = {1},
pages = {16},
pmid = {39838458},
issn = {1741-7007},
mesh = {Humans ; *Melanocytes/metabolism/pathology ; *Uveal Neoplasms/genetics/pathology ; *Melanoma/genetics/pathology ; Uveal Melanoma ; *Mutation ; *Oncogenes ; Retinal Pigment Epithelium/cytology ; *Cell Separation/methods ; },
abstract = {BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumor in adults, arises either de novo from normal choroidal melanocytes (NCMs) or from pre-existing nevi that stem from NCMs and are thought to harbor UM-initiating mutations, most commonly in GNAQ or GNA11. However, there are no commercially available NCM cell lines, nor is there a detailed protocol for developing an oncogene-mutated CM line (MutCM) to study UM development. This study aimed to establish and characterize premalignant CM models from human donor eyes to recapitulate the cell populations at the origin of UM.<br><br>RESULTS: Given the precious value of human donor eyes for studying multiple ocular cell types, we validated a co-isolation protocol of both human NCMs and retinal pigment epithelial (RPE) cells from a single eye. To this end, NCMs and RPE cells were sequentially isolated from 20 donors, with success rates of 95% and 75%, respectively. MutCMs were generated from 10 donors using GNAQ[Q209L]-carried lentivirus with high mutant copies (up to 98.8% of total GNAQ copies being mutant). NCM growth and behavior were characterized under different culture conditions (i.e., supplementation with serum and 12-O-tetradecanoylphorbol-13-acetate) to determine optimized protocols. Particularly, Matrigel&#x2122; coating induced spheroid growth under certain coating thickness and cell seeding density but did not improve NCM metabolic activity. Current methodologies in NCM isolation, culture, and research applications were summarized. Proteomic profiling of 4 NCMs, 1 MutCM, and 3 UMs allowed to discover significant differences in UMs including a downregulation of proteins linked to melanocyte differentiation and an upregulation of proteins involved in RNA metabolism. RNA sequencing revealed enriched pathways related to cancer, notably PI3K-Akt and MAPK signaling pathways, in MutCMs and UM cells compared to NCMs, providing insights into molecular changes in GNAQ[Q209L]-mutated pre-cancer cell models and UM cells.<br><br>CONCLUSIONS: We successfully isolated and established NCM, RPE, and MutCM cell lines. We describe efficient methods for the isolation and growth of NCMs and report their phenotypic, proteomic, and transcriptomic characteristics, which will facilitate the investigation of UM development and progression. The co-isolated RPE cells could benefit research on other ocular pathologies, such as age-related macular degeneration.},
}
@article {pmid39837538,
year = {2025},
author = {Martins, TGDS},
title = {Comment on Artificial Intelligence in Neovascular Age-Related Macular Degeneration.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {9},
pages = {901},
doi = {10.1055/a-2487-5978},
pmid = {39837538},
issn = {1439-3999},
}
@article {pmid39836449,
year = {2025},
author = {Liakopoulos, S and von der Emde, L and Biller, ML and Ach, T and Holz, FG},
title = {Geographic Atrophy in Age-Related Macular Degeneration.},
journal = {Deutsches Arzteblatt international},
volume = {122},
number = {3},
pages = {82-88},
pmid = {39836449},
issn = {1866-0452},
mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy/epidemiology ; *Macular Degeneration/diagnosis/drug therapy/epidemiology ; Germany/epidemiology ; *Complement Inactivating Agents/therapeutic use/administration &amp; dosage ; Treatment Outcome ; Evidence-Based Medicine ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD), a condition of multifactorial origin, is a major cause of irreversible vision loss in industrialized countries. The dry late stage of the disease, known as geographic atrophy (GA), is characterized by progressive loss of photoreceptor cells and retinal pigment epithelial cells in the central retina. An estimated 300 000 to 550 000 people in Germany suffer from GA.<br><br>METHODS: This review is based on pertinent literature retrieved by a selective search in the PubMed and Web of Science databases.<br><br>RESULTS: In 2023, the complement inhibitors pegcetacoplan and avacincaptad pegol were approved in the USA for repeated intravitreal injections and thereby became the first drugs ever approved for the treatment of GA. In Europe, the marketing authorization application for both drugs was withdrawn by the manufacturers after a negative judgment was expressed by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). The EMA stated that the significant slowing of atrophy progression that had been achieved in the approval trials did not lead to any clinically relevant functional benefit for the patients. Further treatment approaches, including gene therapy, are now being studied in clinical trials. There is evidence that micronutrients may slow the progression of atrophy.<br><br>CONCLUSION: In Europe at present, there is no approved treatment for GA due to AMD. There is thus a continuing need for preventive and rehabilitative measures such as smoking cessation, a balanced diet, and magnifying visual aids for patients in the advanced stages of the disease.},
}
@article {pmid39836402,
year = {2025},
author = {Curcio, CA and Messinger, JD and Berlin, A and Sloan, KR and McLeod, DS and Edwards, MM and Bijon, J and Freund, KB},
title = {Fundus Autofluorescence Variation in Geographic Atrophy of Age-Related Macular Degeneration: A Clinicopathologic Correlation.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {1},
pages = {49},
pmid = {39836402},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY006109/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy/diagnosis/pathology ; Female ; *Fluorescein Angiography/methods ; Fundus Oculi ; *Retinal Pigment Epithelium/pathology ; Aged ; Tomography, Optical Coherence/methods ; *Macular Degeneration/pathology/diagnosis ; Aged, 80 and over ; Optical Imaging ; Retinal Drusen/pathology ; },
abstract = {PURPOSE: The purpose of this study was to develop ground-truth histology about contributors to variable fundus autofluorescence (FAF) signal and thus inform patient selection for treating geographic atrophy (GA) in age-related macular degeneration (AMD).<br><br>METHODS: One woman with bilateral multifocal GA, foveal sparing, and thick choroids underwent 535 to 580 nm excitation FAF in 6 clinic visits (11 to 6 years before death). The left eye was preserved 5 hours after death. Eye-tracked ex vivo imaging aligned sub-micrometer epoxy resin sections (n&#xa0;=&#xa0;140, 60 &#xb5;m apart) with clinic data. Light microscopic morphology corresponding to FAF features assessed included drusen-driven atrophy, persistent hyperautofluorescence (hyperFAF) islands and peninsulas within atrophy, and hyperFAF and hypoautofluorescence (hypoFAF) inner junctional zone (IJZ) and outer junctional zone (OJZ) relative to descent of external limiting membrane (ELM). Atrophy growth rate was calculated.<br><br>RESULTS: HypoFAF atrophic spots appeared in association with drusen, and then expanded and coalesced. Over drusen (n&#xa0;=&#xa0;45, all calcified), RPE was continuous and thin, photoreceptors were short or absent, and initially intact ELM descended where RPE was absent. In persistent hyperFAF within atrophy and in the OJZ, the RPE was continuous and dysmorphic, photoreceptors were present and short, and BLamD was thick. In the IJZ, mottled FAF corresponded to dissociated RPE atop persistent BLamD. Overall linear growth rate (0.198 mm/ year) typified multifocal GA.<br><br>CONCLUSIONS: FAF in GA is locally multifactorial, with photoreceptor shortening potentially promoting hyperFAF by increasing incoming excitation light available to RPE fluorophores. RPE dysmorphia may lead to either longer or shorter pathlength for excitation light. At both atrophy initiation and expansion M&#xfc;ller glia are major participants.},
}
@article {pmid39835893,
year = {2025},
author = {Biswas, N and Mori, T and Ragava Chetty Nagaraj, NK and Xin, H and Diemer, T and Li, P and Su, Y and Piermarocchi, C and Ferrara, N},
title = {Adenosine diphosphate stimulates VEGF-independent choroidal endothelial cell proliferation: A potential escape from anti-VEGF therapy.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {4},
pages = {e2418752122},
pmid = {39835893},
issn = {1091-6490},
support = {R35 GM149261/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Cell Proliferation/drug effects ; Mice ; *Choroid/cytology/metabolism/drug effects ; *Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; Cattle ; *Endothelial Cells/drug effects/metabolism/cytology ; *Choroidal Neovascularization/metabolism/pathology/drug therapy ; *Adenosine Diphosphate/pharmacology/metabolism ; Receptors, Purinergic P2Y1/metabolism/genetics ; },
abstract = {We hypothesized that a strategy employing tissue-specific endothelial cells (EC) might facilitate the identification of tissue- or organ-specific vascular functions of ubiquitous metabolites. An unbiased approach was employed to identify water-soluble small molecules with mitogenic activity on choroidal EC. We identified adenosine diphosphate (ADP) as a candidate, following biochemical purification from mouse EL4 lymphoma extracts. ADP stimulated the growth of bovine choroidal EC (BCEC) and other bovine or human eye-derived EC. ADP induced rapid phosphorylation of extracellular signal-regulated kinase in a dose- and time-dependent manner. ADP-induced BCEC proliferation could be blocked by pretreatment with specific antagonists of the purinergic receptor P2Y1 but not with a vascular endothelial growth factor (VEGF) inhibitor, indicating that the EC mitogenic effects of ADP are not mediated by stimulation of the VEGF pathway. Intravitreal administration of ADP expanded the neovascular area in a mouse model of choroidal neovascularization. Single-cell transcriptomics from human choroidal datasets show the expression of P2RY1, but not other ADP receptors, in EC with a pattern similar to VEGFR2. Although ADP has been reported to be a growth inhibitor for vascular EC, here we describe its growth-stimulating effects for BCEC and other eye-derived EC.},
}
@article {pmid39835444,
year = {2025},
author = {Groen, MB and Vestergaard, AH and Cehofski, LJ},
title = {Brolucizumab for treating neovascular age-related macular degeneration: An alternative for treatment-refractory patients.},
journal = {Acta ophthalmologica},
volume = {103},
number = {4},
pages = {e256-e257},
doi = {10.1111/aos.17446},
pmid = {39835444},
issn = {1755-3768},
}
@article {pmid39833712,
year = {2025},
author = {Yu, J and Li, P and Fan, K and Luo, J and Guan, H},
title = {Comparison of different decellularization methods for human anterior lens capsules.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {30},
pmid = {39833712},
issn = {1471-2415},
support = {MS2022011//Scientific Research Project of Nantong Municipal Health Commission/ ; LKM2024015//Scientific Research Project on Elderly Health of Jiangsu Provincial Health Commission/ ; },
mesh = {Humans ; *Epithelial Cells/cytology ; *Anterior Capsule of the Lens/cytology ; *Tissue Engineering/methods ; Cell Survival ; *Tissue Scaffolds ; Cells, Cultured ; },
abstract = {BACKGROUND: Human anterior lens capsules (ALCs) have great potential in the treatment of multiple eye diseases, including corneal ulcers, glaucoma, age-related macular degeneration and macular holes. ALCs are also regarded as promising scaffolds for various ocular cells. Here, we investigated different decellularization methods for removing lens epithelial cells (LECs) that adhered to ALCs.<br><br>METHODS: Human ALCs were treated with various solutions, including 2% lidocaine, 10% sodium chloride, 50% glucose and sterile water. Trypan blue and alizarin red (TB-AR) staining, H&amp;E staining and hydroxyproline assays were used to assess the degree of decellularization. The impacts of acellular ALCs on cell viability and cell-tissue interaction were investigated in vitro.<br><br>RESULTS: These findings revealed that 2% lidocaine, 10% sodium chloride, 50% glucose, and sterile water had the capacity to decellularize ALCs at 37&#xa0;&#xb0;C. The structure of ALCs in all decellularization groups was similar to that of intact ALCs. The effects of 10% sodium chloride and sterile water on decellularization were significantly better than those of 2% lidocaine and 50% glucose. The H&amp;E staining revealed that the different decellularization methods maintained the integrity of the lens capsular structure. Compared with sterile water, 10% sodium chloride preserved a better level of hydroxyproline. The ALCs in the 10% sodium chloride-treated group and the sterile water-treated group were shown to be suitable for cell adhesion in vitro.<br><br>CONCLUSION: This study identified two optimal decellularization methods for acellular ALCs: using 10% sodium chloride and using sterile water. The obtained acellular ALCs could be promising scaffolds for ocular cells. In addition, acellular ALCs do not need resterilization and may be directly used for autologous lens capsule transplantation in clinical applications.},
}
@article {pmid39833576,
year = {2025},
author = {Ong, AY and Hogg, HDJ and Keane, PA},
title = {Cochrane corner: artificial intelligence for diagnosing exudative age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {4},
pages = {620-621},
pmid = {39833576},
issn = {1476-5454},
}
@article {pmid39833572,
year = {2025},
author = {Hagag, AM and Holmes, C and Raza, A and Riedl, S and Anders, P and Kaye, R and Prevost, T and Fritsche, LG and Rueckert, D and Bogunović, H and Scholl, HPN and Schmidt-Erfurth, U and Lotery, AJ and Sivaprasad, S},
title = {Features of intermediate and late dry age-related macular degeneration on adaptive optics ophthalmoscopy: Pinnacle Study Report 8.},
journal = {Eye (London, England)},
volume = {39},
number = {6},
pages = {1211-1216},
pmid = {39833572},
issn = {1476-5454},
support = {/WT_/Wellcome Trust/United Kingdom ; 210572/Z/18/Z//Wellcome Trust (Wellcome)/ ; },
mesh = {Humans ; *Ophthalmoscopy/methods ; Prospective Studies ; Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Geographic Atrophy/diagnosis ; Aged, 80 and over ; Retinal Pigment Epithelium/pathology ; Middle Aged ; Retinal Cone Photoreceptor Cells/pathology ; Disease Progression ; },
abstract = {BACKGROUND/OBJECTIVES: Adaptive optics ophthalmoscopy (AOO) has the potential to provide insights into AMD pathology and to assess the risk of progression. We aim to utilise AOO to describe detailed features of intermediate AMD and to characterise microscopic changes during atrophy development.<br><br>SUBJECTS/METHODS: Patients with intermediate AMD were recruited into PINNACLE, a prospective observational cohort study. Participants underwent flood-illumination AOO using the commercially available rtx1 camera. AOO images were qualitatively assessed and correlated with clinical imaging including optical coherence tomography (OCT) and infrared scanning laser ophthalmoscopy.<br><br>RESULTS: The visibility of cone mosaic was generally compromised in eyes with intermediate AMD. We observed an association between the visibility of cone mosaic on AOO and the detection of a well-defined normal interdigitation zone on OCT. Drusen subtypes were identified on AOO as variations in reflectance at the edge and/or the centre of the druse. The absence of a hyperreflective margin was associated with the loss of the overlying ellipsoid zone on OCT prior to the collapse of the druse. With progressive attenuation of the retinal pigment epithelium and loss of photoreceptor layers, the drusenoid lesion appeared more hyperreflective with very distinctive edges.<br><br>CONCLUSIONS: This cross-sectional study supports the potential value of AOO for providing information on intermediate AMD and the development of atrophic lesions that cannot be seen in conventional imaging modalities. The ongoing longitudinal PINNACLE study is assessing the significance of the described findings.},
}
@article {pmid39832055,
year = {2025},
author = {Yuan, CY and Zuo, L and Dong, YC and Liu, BX and Qi, H},
title = {Secretogranin III: a promising therapeutic target for intraocular neovascular lesions.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {26},
pmid = {39832055},
issn = {1573-2630},
mesh = {Humans ; *Chromogranins/biosynthesis/metabolism ; *Choroidal Neovascularization/metabolism/drug therapy ; *Retinal Neovascularization/metabolism/drug therapy ; },
abstract = {PURPOSE: The purpose of this study is to investigate the role of Secretogranin III (Scg3) in the pathogenesis of intraocular neovascular diseases and assess its potential as a therapeutic target for novel treatment strategies.<br><br>METHODS: A literature review was conducted to examine the expression of Scg3 in intraocular neovascular diseases. We reviewed studies on the interaction of Scg3 with its homologous receptors and its effect on endothelial cell proliferation, migration, and vascular permeability-key processes involved in angiogenesis and neovascularization.<br><br>RESULTS: Scg3 was found to be upregulated in the tissues affected by diabetic retinopathy (DR), retinopathy of prematurity (ROP), and choroidal neovascularization. In DR, Scg3 expression was linked to retinal neovascularization, where it facilitated endothelial cell proliferation and migration, essential processes for the formation of new blood vessels. Similarly, in ROP, Scg3 was associated with fibrovascular tissue proliferation within avascular retinal zones, contributing to the pathological neovascularization seen in premature infants. In the context of age-related macular degeneration (AMD), Scg3 appeared to play a role in choroidal neovascularization, where it promoted the invasion of choroidal capillaries into the retinal pigment epithelium. Furthermore, Scg3's binding to its homologous receptors was shown to enhance vascular permeability, potentially exacerbating fluid leakage and edema in these diseases, which is a hallmark of exudative conditions. Collectively, these findings suggest that Scg3 plays a pivotal role in driving angiogenesis and vascular permeability in intraocular neovascular diseases CONCLUSION: The upregulation of Scg3 in DR, ROP, and choroidal neovascularization highlights its potential as a novel therapeutic target. Inhibition of Scg3 could offer a new avenue for treating these sight-threatening conditions.},
}
@article {pmid39832028,
year = {2025},
author = {Acar, N and Pehlivanoğlu, S},
title = {High dose aflibercept treatment in naive neovascular age-related macular degeneration.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {24},
pmid = {39832028},
issn = {1573-2630},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Female ; Male ; Intravitreal Injections ; Retrospective Studies ; Aged ; Middle Aged ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; Follow-Up Studies ; *Wet Macular Degeneration/drug therapy/diagnosis ; Treatment Outcome ; Dose-Response Relationship, Drug ; Fluorescein Angiography ; Angiogenesis Inhibitors/administration &amp; dosage ; Fundus Oculi ; *Macula Lutea/pathology ; },
abstract = {BACKGROUND: To evaluate the efficacy and safety of intravitreal injections of 4 mg (high dose) of aflibercept in treatment-naive patients with neovascular AMD(nAMD) with treat and extend(TREX) dosing regimens, and to determine the frequency of injections.<br><br>METHODS: In this interventional, retrospective study a total of 15 eyes of 14 patients (eight female and 9 male) with nAMD were included. All patients were examined and OCT imaging was performed at the time of initial presentation, on the day of each injection and at subsequent follow-up visits. Each eye received intravitreal injections of 4&#xa0;mg/0.1&#xa0;mL aflibercept at the dose of every 4&#xa0;weeks for three months (loading phase) after that 4&#xa0;mg high dose of aflibercept was applied as the TREX regime. The eyes with a minimum follow-up time of 12&#xa0;months are included.<br><br>RESULTS: The mean age of the patients was 74.9&#x2009;&#xb1;&#x2009;7.3(61-85) years and the mean follow-up time was 20.33&#x2009;&#xb1;&#x2009;8.7(12-34) months. Total number of injections were 9.3&#x2009;&#xb1;&#x2009;3.0 (5-14) during the follow-up period. A statistically significant increase was found in terms of best-corrected visual acuity and central macular thickness between mean baseline values and at 1, 3, 6, 12&#xa0;months, and the final examination(p&#x2009;<&#x2009;0.05 for each comparison). No complication was observed during follow-up.<br><br>CONCLUSIONS: High-dose Aflibercept of 4&#xa0;mg/0.1&#xa0;mL application with the TREX regimen was found to be efficient and safe. High-dose may also help to reduce the frequency of injections and visits in the follow-up period in eyes with nAMD. Prospective studies with large series are warranted.},
}
@article {pmid39831769,
year = {2025},
author = {Purola, P and Koskinen, S and Kaarniranta, K and Uusitalo, H},
title = {Neovascular age-related macular degeneration on three nationwide survey and register data in Finland during 2000-2017.},
journal = {Acta ophthalmologica},
volume = {103},
number = {4},
pages = {449-460},
doi = {10.1111/aos.17444},
pmid = {39831769},
issn = {1755-3768},
support = {//Elsemay Bj&#xf6;rn Rahasto/ ; //Finnish Federation of the Visually Impaired/ ; //Tampereen seudun N&#xe4;k&#xf6;vammaisten tukis&#xe4;&#xe4;ti&#xf6; s.r/ ; //Sokeain Yst&#xe4;v&#xe4;t/ ; //Emil Aaltosen S&#xe4;&#xe4;ti&#xf6;/ ; //Juho Vainion S&#xe4;&#xe4;ti&#xf6;/ ; },
mesh = {Humans ; Finland/epidemiology ; Male ; Female ; *Registries ; Middle Aged ; Aged ; Incidence ; *Visual Acuity ; Cross-Sectional Studies ; Prevalence ; *Wet Macular Degeneration/epidemiology/drug therapy/diagnosis ; Intravitreal Injections ; Adult ; *Health Surveys ; Follow-Up Studies ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Retrospective Studies ; *Quality of Life ; },
abstract = {PURPOSE: To evaluate time trends in the incidence and prevalence of neovascular age-related macular degeneration (nAMD) and its treatments, associated factors, and effects on vision in Finland during 2000-2017.<br><br>METHODS: We used three nationwide health examination surveys representing the Finnish population aged 30&#x2009;years or older. All three surveys were linked to the national care register covering nAMD diagnoses and intravitreal injections between 2000 and 2017. All three surveys included a health examination in which distance and near visual acuity (VA) were measured, as well as self-reported and register-based information on socio-demographic status and lifestyle, health care use, co-morbidities, and quality of life. The data included two cross-sectional time points in 2011 and 2017 and two 11&#x2009;year longitudinal follow-ups during 2000-2011 and 2006-2017.<br><br>RESULTS: The incidence and prevalence of nAMD were two times higher in women than in men. The annual prevalence of nAMD increased from 0.51% to 0.70% and from 0.22% to 0.46% in treated nAMD between 2011 and 2017. Treated nAMD patients had an average of 4 intravitreal injections per treatment year. nAMD patients showed significantly poorer distance and near VA than persons without any AMD in 2011 and 2017 (p&#x2009;<&#x2009;0.001). However, near VA was significantly better in 2017 than in 2011 among nAMD patients (p&#x2009;=&#x2009;0.036). The duration of nAMD showed weak negative correlation with distance and near VA. After adjusting for age and sex, nAMD patients showed significantly higher univariable odds ratios for lower distance VA, low consumption of vegetables, living in central Finland, a higher number of hospitalisations per year, and older age compared with persons without any AMD.<br><br>CONCLUSION: Since nAMD is an increasing burden for public health with gender discrepancy and a detrimental impact on vision, we should better find patients who have a high risk of developing nAMD and try to optimise their preventive intervention. Once nAMD is developed, we should understand treatment and follow-up demands at the personalised level. The nationwide register data help us in those challenges.},
}
@article {pmid39831067,
year = {2025},
author = {Eriksen, NS and Mousavi, N and Subhi, Y and Sørensen, TL and Krogh Nielsen, M},
title = {Charles Bonnet syndrome in patients with geographic atrophy secondary to age-related macular degeneration: a cross-sectional study.},
journal = {Therapeutic advances in ophthalmology},
volume = {17},
number = {},
pages = {25158414241305500},
pmid = {39831067},
issn = {2515-8414},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a prevalent cause of irreversible vision loss among the elderly. The prevalence and detailed characteristics of Charles Bonnet syndrome (CBS) remain largely unexplored in patients with geographic atrophy (GA) secondary to AMD.<br><br>OBJECTIVES: To investigate the prevalence and characteristics of CBS in patients with GA secondary to AMD.<br><br>DESIGN: Prospective cross-sectional study.<br><br>METHODS: A total of 149 patients with GA secondary to AMD were previously screened and examined for clinical studies. These patients were then prospective contacted by telephone for this study, and 120 patients responded and agreed to do an interview on symptoms of CBS. All with CBS were inquired about detailed characteristics of their hallucinations.<br><br>RESULTS: Patients with GA secondary to AMD were aged 82.1&#x2009;&#xb1;&#x2009;6.2&#x2009;years and 62% were of female biological sex. The prevalence of CBS was 25 in 120 (20.8%). Thirteen (52%) of those with CBS were not previously informed of the disease. We found no difference between those with and without CBS in terms of age, biological sex, hearing difficulties, whether living alone or with others, co-morbidity of psychiatric or neurological diseases, or psychotropic use. Characteristics of the visual hallucinations were reported to occur at various frequencies from daily to less than monthly, occur during various times of the day, and almost always last minutes at most. Ten in 25 (40%) had not told anyone of having CBS.<br><br>CONCLUSION: One in five with GA has CBS, which ranks GA as an eye disease with one of the highest reported prevalences of CBS. The condition presents with a significant variation across the patient group. A very large proportion of those with CBS were not informed of the disease and had never told anyone of their condition by their own initiative.},
}
@article {pmid39830553,
year = {2024},
author = {Parakh, S and Bhatt, V and Das, S and Lakhlan, P and Luthra, G and Luthra, S},
title = {Intraocular Inflammation Following Intravitreal Faricimab Injection in Neovascular Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e75937},
pmid = {39830553},
issn = {2168-8184},
abstract = {We herein report intraocular inflammation (IOI) following intravitreal (IVT) faricimab injection in three patients. A 73-year-old male, a 68-year-old female, and an 82-year-old female, all diagnosed with neovascular age-related macular degeneration (AMD), had received multiple anti-vascular endothelial growth factor (anti-VEGF) injections for the same. They were injected with IVT faricimab due to non-response to other agents. Following IVT faricimab, two patients presented with mild vitritis (grade 2) within three days post-injection, and one patient presented with anterior uveitis on day 1. No associated retinal vasculitis or occlusion was present. All patients responded well to topical steroid therapy. Notably, the 68-year-old lady had a history of IOI (mild vitritis) following a single IVT brolucizumab in the past. The other two patients had not received IVT brolucizumab earlier. IOI after IVT faricimab has been reported a few times previously. One must be aware of the spectrum of presentation (vitritis, anterior uveitis, panuveitis, vascular occlusion, vasculitis) and be vigilant to provide timely management, especially in sight-threatening cases. A history of IOI following previous brolucizumab injection needs to be evaluated further for possible immunological mechanisms at play.},
}
@article {pmid39829629,
year = {2025},
author = {Costa, I and Carvalho, A and Andrade, H and Pereira, B and Camacho, P},
title = {Neurodegeneration and choroidal vascular features on OCT in the progression to advanced age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {18},
number = {1},
pages = {103-110},
pmid = {39829629},
issn = {2222-3959},
abstract = {AIM: To quantify and compare longitudinal thickness changes of the ganglion cell complex (GCC) and the choroid in patients with different patterns of age-related macular degeneration (AMD) progression.<br><br>METHODS: Retrospective cohort analysis of anonymized data from participants aged 50y or more and diagnosed with early/intermediate AMD in at least one eye (with no evidence of advanced AMD). A total of 64 participants were included from the Instituto de Retina de Lisboa (IRL) study (IPL/2022/MetAllAMD_ESTeSL) and divided into 4 groups according to the Rotterdam classification for AMD. Spectral domain optical coherence tomography (SD-OCT) was used to assess and quantify GCC and choroid thickness at two time points (first visit vs last visit) with a minimum interval of 3y.<br><br>RESULTS: In the GCC inner ring, a thinner thickness (P=0.001) was observed in the atrophic AMD group (51.3&#xb1;21.4 &#xb5;m) compared to the early AMD (84.3&#xb1;11.5 &#xb5;m), intermediate AMD (77.6&#xb1;16.1 &#xb5;m) and neovascular AMD (88.9&#xb1;16.3 &#xb5;m) groups. Choroidal thickness quantification showed a generalized reduction in the central circle (P=0.002) and inner ring (P=0.001). Slight reductions in retinal thickness were more accentuated in the inner ring in the atrophic AMD (-13%; P<0.01).<br><br>CONCLUSION: The variation of the analyzed structures could be an indicator of risk of progression with neurodegenerative (GCC) or vascular (choroid) pattern in the intermediate and atrophic AMD. The quantification of both structures can provide important information about the risk of disease progression in the early and intermediate stages but also for the evolution pattern into late stages (atrophic or neovascular).},
}
@article {pmid39829617,
year = {2025},
author = {Meng, NN and Xia, LZ and Gong, YQ and Lu, PR},
title = {Autophagy serves as a protective effect against inflammatory injury of oxidative stress in ARPE-19 cell.},
journal = {International journal of ophthalmology},
volume = {18},
number = {1},
pages = {28-38},
pmid = {39829617},
issn = {2222-3959},
abstract = {AIM: To test the effect of autophagy on inflammatory damage resulting from oxidative stress in adult retinal pigment epithelial cell line (ARPE-19).<br><br>METHODS: ARPE-19 cells were pretreated with 200 and 600 &#xb5;mol/L hydrogen peroxide (H2O2) at various time intervals. The changes of cell morphology, cell viability, reactive oxygen species (ROS) level, autophagic activity, and the inflammatory cytokines (TNF&#x3b1;, IL-6, and TGF&#x3b2;) were measured at baseline and after treatment with autophagy inducer rapamycin (Rapa) and suppressor wortmannin (Wort) or shATG5.<br><br>RESULTS: The levels of ROS, cytokines (TNF&#x3b1;, IL-6, and TGF&#x3b2;), and autophagic activity were significantly increased in ARPE-19 cells after pretreated with H2O2 (all P<0.05) and IL-10 was significantly decreased (P<0.05). By upregulating autophagy, Rapa significantly reduced oxidative stress-induced secretion of pro-inflammatory factors (TNF&#x3b1; and IL-6) and ROS (all P<0.05), yet elevated the production of TGF&#x3b2; (P<0.05). In contrast, suppression of autophagy through Wort or ATG5 knockdown reduced cell viability, increased cell apoptotic rate, and exacerbated the generation of ROS and inflammatory cytokines (TNF&#x3b1;, IL-6, and TGF&#x3b2;; all P<0.05).<br><br>CONCLUSION: Autophagy demonstrates a protective effect on ARPE-19 cell through mitigating oxidative damage and oxidative stress-induced inflammatory response. Regulation of autophagy may be a potential way for age-related macular degeneration.},
}
@article {pmid39829614,
year = {2025},
author = {Zhong, HM and Shen, BQ and Chen, YH and Zhao, XH and Huang, XX and Zhou, MW and Sun, XD},
title = {IL-17A mediates inflammation-related retinal pigment epithelial cells injury via ERK signaling pathway.},
journal = {International journal of ophthalmology},
volume = {18},
number = {1},
pages = {15-27},
pmid = {39829614},
issn = {2222-3959},
abstract = {AIM: To investigate whether interleukin-17A (IL-17A) gets involved in the mechanisms of inflammation-related retinal pigment epithelium (RPE) cells injury and its significance in age-related macular degeneration (AMD).<br><br>MRTHODS: A sodium iodate (NaIO3) mouse model as well as IL-17A [-/-] mice were established. The effects of inflammatory cytokines in RPE cells and retinal microglia before and after NaIO3 modeling in vivo and in vitro, were investigated using immunofluorescence, immunoprotein blotting, and quantitative real-time fluorescence polymerase chain reaction (qRT-PCR), respectively. Interventions using recombinant IL-17A protein (rIL-17A) or IL-17A neutralizing antibody (IL-17A NAb) were used to observe the subsequent differences in fundus, fundus photography and optical coherence tomography (OCT), cell viability, and expression of oxidative stress-related markers before and after modeling, and to screen for key signaling pathways.<br><br>RESULTS: In the scenario of NaIO3 stimulation, RPE cells obviously tended to degenerate. Simultaneously proliferation and activation of retinal microglia was confirmed in NaIO3-stimulated mice, whereas such effects induced by NaIO3 were significantly ameliorated with IL-17A NAb intervention or in IL-17A [-/-] mice. In addition, IL-17A promoted the proliferation and activation of microglia as well as oxidative damage and the secretion of inflammatory cytokines alongside NaIO3-induced damage in RPE cells in vivo and ex vivo. Meanwhile, the extracellular signal-regulated kinase (ERK) signaling pathway was shown to be participated in the regulation of NaIO3-induced RPE cells injury mediated by IL-17A in vivo and ex vivo, as IL-17A-induced inflammatory cytokines release in the NaIO3 model was alleviated after blocking the ERK pathway.<br><br>CONCLUSION: IL-17A probably promotes the NaIO3-induced RPE cells injury through exacerbating inflammation in terms of retinal microglia activation and inflammatory cytokines release via ERK signaling pathway. Inhibition of IL-17A may be a new potential target for dry AMD treatment.},
}
@article {pmid39828006,
year = {2025},
author = {Ţurcaş, C and Nicoară, SD},
title = {A comprehensive review of structure-function correlations in age-related macular degeneration: Contributions of microperimetry.},
journal = {Survey of ophthalmology},
volume = {70},
number = {3},
pages = {426-450},
doi = {10.1016/j.survophthal.2025.01.009},
pmid = {39828006},
issn = {1879-3304},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Visual Field Tests/methods ; *Macular Degeneration/physiopathology/diagnosis ; Fluorescein Angiography ; *Visual Fields/physiology ; Visual Acuity/physiology ; *Retina/physiopathology/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness worldwide. High-resolution imaging techniques have been pivotal in characterizing the morphological alterations in the retina and in identifying structural biomarkers with prognostic significance. In clinical practice, visual function is primarily assessed through visual acuity testing, which, however, does not completely reflect the functional deficits experienced by patients. Microperimetry provides a more comprehensive evaluation of macular function, enabling a direct correlation with retinal structure. We examine the current literature on the correlation between morphological biomarkers - identified via optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence - and retinal sensitivity, as assessed by microperimetry. By encompassing all stages of AMD, we explore the association between retinal sensitivity and a broad spectrum of structural parameters, including distinct drusen phenotypes, hyperreflective foci, the integrity and thickness of various retinal layers, the junctional zone of geographic atrophy, exudative features of neovascular AMD, choriocapillaris flow deficits, and diverse patterns of autofluorescence, among numerous other relevant structural markers. By offering a deeper understanding of the structure-function correlations in disease progression, we provide critical up-to-date insights into the underlying mechanisms of AMD. Moreover, as novel therapeutic strategies continue to emerge, these correlations may serve as more robust endpoints for future clinical trials.},
}
@article {pmid39825687,
year = {2025},
author = {Han, F and Li, X and Tao, T and Wang, J},
title = {A pharmacovigilance study on the safety of faricimab in real-world scenario using FDA adverse event reporting system database.},
journal = {Expert opinion on drug safety},
volume = {24},
number = {6},
pages = {657-664},
doi = {10.1080/14740338.2025.2456173},
pmid = {39825687},
issn = {1744-764X},
mesh = {Humans ; *Adverse Drug Reaction Reporting Systems/statistics &amp; numerical data ; United States ; *Pharmacovigilance ; Databases, Factual ; United States Food and Drug Administration ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: Faricimab is predominantly prescribed for conditions such as age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema related to retinal vein occlusion (RVO-ME). Currently, a notable absence of large-scale, real-world studies focusing on the adverse reactions of faricimab exists.<br><br>METHODS: This study assesses the side effects of faricimab by analyzing reports of adverse events (AEs) from the FDA's AE Reporting System (FAERS) database. Through disproportionality analysis, this study substantiates the drug's safety oversight.<br><br>RESULTS: Our study revealed 2,746 instances of adverse events linked to faricimab, spanning 21 system organ classes (SOCs). The study retained 121 significant disproportionality preferred terms (PTs) that met criteria across all four analytical methods. Faricimab-associated AEs not documented in the drug instructions included visual impairment, blindness, retinal hemorrhage, anterior chamber inflammation, keratic precipitates, dry eye, chorioretinitis, diabetic retinopathy, and others.<br><br>CONCLUSION: The majority of our results align with earlier clinical studies and the details outlined in the product's manual. Additionally, we identified several unforeseen and potential AE signals related to faricimab use. These insights are instrumental for ongoing clinical surveillance and risk assessment associated with the drug.},
}
@article {pmid39824523,
year = {2025},
author = {Wong, DT and Aboobaker, S and Maberley, D and Sharma, S and Yoganathan, P},
title = {Switching to faricimab from the current anti-VEGF therapy: evidence-based expert recommendations.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {39824523},
issn = {2397-3269},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Antibodies, Bispecific/therapeutic use/administration &amp; dosage ; Evidence-Based Medicine ; *Drug Substitution ; *Diabetic Retinopathy/drug therapy ; *Wet Macular Degeneration/drug therapy ; *Macular Edema/drug therapy ; Visual Acuity ; },
abstract = {Dual inhibition of the angiopoietin (Ang)/Tie and vascular endothelial growth factor (VEGF) signalling pathways in patients with retinal diseases, such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME), may induce greater vascular stability and contribute to increased treatment efficacy and durability compared with treatments that only target the VEGF pathway. Faricimab, a bispecific intravitreal agent that inhibits both VEGF and Ang-2, is the first injectable ophthalmic drug to achieve treatment intervals of up to 16 weeks in Phase 3 studies for nAMD and DME while exhibiting improvements in visual acuity and retinal thickness. Data from real-world studies have supported the safety, visual and anatomic benefits and durability of faricimab, even in patients who were previously treated with other intravitreal agents. These evidence-based expert recommendations from a panel of retina specialists consolidate current evidence with clinical experience for the optimal use of faricimab in patients with nAMD or DME, with a focus on switching from an anti-VEGF agent to faricimab.},
}
@article {pmid39824296,
year = {2025},
author = {Forte, P and Paques, M and Cattaneo, J and Dupas, B and Castro-Farias, D and Girmens, JF and Siab, M and Biagini, F and Nicolò, M and Eandi, CM and Sacconi, R and Querques, G},
title = {Perifoveal vascular anomalous complex and telangiectatic capillaries: An overview of two entities potentially sharing a common pathophysiology.},
journal = {Survey of ophthalmology},
volume = {70},
number = {3},
pages = {369-379},
doi = {10.1016/j.survophthal.2025.01.007},
pmid = {39824296},
issn = {1879-3304},
mesh = {Humans ; *Retinal Telangiectasis/physiopathology/diagnosis ; *Capillaries/abnormalities/pathology ; *Retinal Vessels/abnormalities ; Fluorescein Angiography/methods ; Tomography, Optical Coherence ; *Fovea Centralis/blood supply ; Diagnosis, Differential ; *Vascular Malformations/physiopathology/diagnosis ; },
abstract = {Focal capillary ectasia in the macular region can manifest in distinct clinical scenarios, which can be categorized into 2 main entities: perifoveal vascular anomalous complex (PVAC) and telangiectatic capillaries (TelCaps). PVAC represents a primary, idiopathic condition, whereas TelCaps occur secondary to underlying vascular disorders, including diabetic macular edema and retinal vein occlusion. We provide a comprehensive analysis of these 2 entities, encompassing their clinical presentations, multimodal imaging findings, histological evidence, and differential diagnosis from other retinal microvascular abnormalities, such as Type 1 macular telangiectasia, adult-onset Coats disease, Type 3 macular neovascularization in age-related macular degeneration, and retinal arterial macroaneurysms. Although PVAC and TelCaps are distinct entities, they may share common pathogenic mechanisms, including progressive endothelial dysfunction, pericyte loss, and intraluminal deposition of blood components. Selective laser photocoagulation has emerged as a promising therapeutic approach for both conditions. The proposed standardization of nomenclature for accurate reporting and meaningful cross-study comparisons is expected to facilitate future advancements in this field, ultimately leading to improved patient outcomes.},
}
@article {pmid39824255,
year = {2025},
author = {Ruamviboonsuk, P and Ng, DSC and Chaikitmongkol, V and Chang, A and Chen, SJ and Chen, Y and Cheung, CMG and Gomi, F and Guymer, R and Kim, JE and Koh, A and Kokame, GT and Lai, CC and Lai, TYY and Lee, WK and Ogura, Y and Sadda, S and Teo, KYC and Wong, TY and Yanagi, Y and Lam, DSC},
title = {Consensus and guidelines on diagnosis and management of polypoidal choroidal vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {14},
number = {1},
pages = {100144},
doi = {10.1016/j.apjo.2025.100144},
pmid = {39824255},
issn = {2162-0989},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Asia ; *Choroid/blood supply ; *Choroid Diseases/diagnosis/therapy ; *Choroidal Neovascularization/diagnosis/therapy ; *Consensus ; *Disease Management ; Fluorescein Angiography/methods ; Polypoidal Choroidal Vasculopathy ; *Polyps/diagnosis/therapy ; *Practice Guidelines as Topic ; *Societies, Medical ; Tomography, Optical Coherence/methods ; },
abstract = {A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV. Furthermore, non-indocyanine green angiography features in optical coherence tomography angiography have been validated for PCV diagnosis and treatment response monitoring. Clinical trials provide new data on the safety and efficacy of various anti-vascular endothelial growth factor (anti-VEGF) agents as well as protocols that aim to improve the sustainability of treatments. In view of the myriads of emerging information, the panel gathered, reviewed, discussed, formulated and voted on the consensus and guidelines of PCV on four areas: 1) disease entity, 2) investigation and diagnosis, 3) treatment options, and 4) management protocol and future development in a five-point Likert scale (strongly agree, agree, neutral, disagree and strongly disagree). We proposed using a consensus score in which the maximum was 100. The summation of the respective "percentages" of experts voting for "agree" or "strongly agree" would be counted as the actual score. Consensus was achieved when the actual score of 75 or more was reached, which meant at least 75 % of the experts had voted for "strongly agree" or "agree" on the consensus statement concerned.},
}
@article {pmid39823618,
year = {2025},
author = {Alla, DA and Gerges, L and Philip, J and Wirth, C},
title = {Supplements to Slow Progression of Age-Related Macular Degeneration.},
journal = {American family physician},
volume = {111},
number = {1},
pages = {73-74},
pmid = {39823618},
issn = {1532-0650},
}
@article {pmid39820891,
year = {2025},
author = {Charbel Issa, P and De Silva, SR and Pfau, K and Birtel, J},
title = {Differential Diagnosis of Age-Related Macular Degeneration.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {1},
pages = {7-21},
doi = {10.1055/a-2327-8597},
pmid = {39820891},
issn = {1439-3999},
mesh = {Humans ; Diagnosis, Differential ; *Macular Degeneration/diagnosis ; Retinal Drusen/diagnosis ; },
abstract = {A diagnosis of age-related macular degeneration (AMD) may have a significant impact on a patient's life. Therefore, it is important to consider differential diagnoses, as these can differ considerably from AMD regarding prognosis, inheritance, monitoring and therapy. Differential diagnoses include other macular diseases with drusen, drusen-like changes, monogenic retinal dystrophies, as well as a wide range of other, often rare macular diseases. In this review, clinical examples are presented that illustrate alternative diagnoses to AMD and when these should be considered. These include, amongst others, patients with autosomal dominant drusen, Sorsby fundus dystrophy, pachydrusen, late-onset Stargardt disease, extensive macular atrophy with pseudodrusen (EMAP), pseudoxanthoma elasticum (PXE), North Carolina macular dystrophy, mitochondrial retinopathy, benign yellow dot maculopathy, dome- or ridge-shaped maculopathy, or macular telangiectasia type 2.},
}
@article {pmid39819986,
year = {2025},
author = {},
title = {Valeda Light Delivery System for age-related macular degeneration.},
journal = {The Medical letter on drugs and therapeutics},
volume = {67},
number = {1720},
pages = {9-10},
doi = {10.58347/tml.2025.1720a},
pmid = {39819986},
issn = {1523-2859},
}
@article {pmid39819528,
year = {2025},
author = {Pandey, S and Gupta, A and Mahato, DK and Paul, V and Tripathi, AD and Rasane, P and Kumar, P and Kamle, M and Haque, S},
title = {Lutein and Zeaxanthin: Source, Extraction, Stability, Bioactivity, and Functional Food Applications.},
journal = {Current pharmaceutical biotechnology},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113892010334209241206113640},
pmid = {39819528},
issn = {1873-4316},
abstract = {Nature has been acknowledged as a fundamental source of diverse bioactive molecules. Among natural carotenoids, lutein, zeaxanthin, and their oxidative metabolites are specifically deposited in the macular region of living organisms. Lutein and zeaxanthin are carotenoids primarily found in green leafy vegetables, eggs, and various fruits. Lutein and zeaxanthin emerge as the primary carotenoids in the retina, playing a crucial role as photo-protectants to prevent retinal degeneration. The extraction of lutein and zeaxanthin from natural sources involves several techniques, including solvent extraction and supercritical fluid extraction, with an emphasis on optimizing efficiency and yield. Incorporating these carotenoids into functional foods-such as fortified dairy products, baked goods, and snacks-enhances their nutritional profiles and provides significant health benefits. This review examines the sources, stability, bioactivity, and various extraction methods for lutein and zeaxanthin, highlighting their potential for photoprotection, antioxidant activity, and antidiabetic effects. These attributes, combined with innovative extraction techniques, position lutein and zeaxanthin as promising ingredients for functional food applications.},
}
@article {pmid39819346,
year = {2025},
author = {Heier, JS and Lad, EM and Holz, FG and Rosenfeld, PJ and Guymer, RH and Boyer, D and Grossi, F and Baumal, CR and Korobelnik, JF and Slakter, JS and Waheed, NK and Metlapally, R and Pearce, I and Steinle, N and Francone, AA and Hu, A and Lally, DR and Deschatelets, P and Francois, C and Bliss, C and Staurenghi, G and Monés, J and Singh, RP and Ribeiro, R and Wykoff, CC},
title = {Pegcetacoplan for the treatment of geographic atrophy due to age-related macular degeneration: a plain language summary of OAKS and DERBY clinical studies.},
journal = {Immunotherapy},
volume = {17},
number = {9},
pages = {609-623},
doi = {10.1080/1750743X.2025.2449760},
pmid = {39819346},
issn = {1750-7448},
}
@article {pmid39818644,
year = {2025},
author = {Fleckenstein, M},
title = {Insights into Alcohol and Age-related Macular Degeneration Progression.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {3},
pages = {197-199},
doi = {10.1016/j.oret.2024.12.017},
pmid = {39818644},
issn = {2468-6530},
}
@article {pmid39818360,
year = {2025},
author = {Feo, A and Stradiotto, E and Govetto, A and Forte, P and Boscia, G and Nicolò, M and Cattaneo, J and Eandi, CM and Angi, M and Ramtohul, P and Romano, MR},
title = {Bacillary layer detachment: Updates on its clinical and prognostic significance in retinal disease.},
journal = {Survey of ophthalmology},
volume = {70},
number = {3},
pages = {401-411},
doi = {10.1016/j.survophthal.2025.01.005},
pmid = {39818360},
issn = {1879-3304},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Detachment/diagnosis/etiology ; Prognosis ; *Retinal Photoreceptor Cell Inner Segment/pathology ; },
abstract = {Bacillary layer detachment (BALAD) refers to the distinctive splitting at the level of the photoreceptor inner segment myoid and accumulation of intraretinal fluid, as seen on optical coherence tomography (OCT). BALAD is an increasingly recognized OCT biomarker of numerous heterogeneous chorioretinal diseases, including posterior uveitis, age-related macular degeneration and macular neovascularization, neoplastic and paraneoplastic retinal disorders, rhegmatogenous retinal detachment, blunt ocular trauma, and miscellaneous conditions. The recognition of BALAD is clinically relevant because, based on the specific etiology, BALAD may require simple observation, ocular or systemic medical treatment, or even surgical intervention, with subsequent different prognosis. We discuss and summarize the clinical and prognostic significance of BALAD in the different chorioretinal disorders in which it has been described.},
}
@article {pmid39818249,
year = {2025},
author = {Lee, Y and Ahn, EJ and Chae, SW and Hussain, AA},
title = {Triterpenoid saponin-mediated recovery of visual deficits in age-related macular degeneration (AMD): Double-blind, placebo-controlled, randomised clinical trial.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {14},
number = {1},
pages = {100143},
doi = {10.1016/j.apjo.2025.100143},
pmid = {39818249},
issn = {2162-0989},
mesh = {Humans ; Double-Blind Method ; Male ; Female ; *Saponins/therapeutic use/administration &amp; dosage ; Aged ; *Macular Degeneration/physiopathology/drug therapy ; *Triterpenes/therapeutic use ; Visual Acuity/physiology ; Dark Adaptation/physiology ; Aged, 80 and over ; Middle Aged ; Retinal Rod Photoreceptor Cells/physiology/drug effects ; Visual Fields/physiology ; *Recovery of Function ; *Vision Disorders/drug therapy/physiopathology ; },
abstract = {PURPOSE: Recovery rate of rod photoreceptor sensitivity (S2 gradient) following a bleach is reduced in age-related macular degeneration (AMD) due to diminished delivery of retinol across a grossly altered Bruch's membrane. Since triterpenoid saponins are known to improve transport across Bruch's, we have assessed their possible use for reversing the visual deficits in AMD.<br><br>DESIGN: Double-blind, placebo controlled randomised clinical trial.<br><br>METHODS: Altogether 11 AMD patients and seven age-matched control subjects were recruited to undertake a small proof-of-principle study. Dark adaptation curves were obtained and S2 gradients evaluated using a Humphrey Field Analyser. Following basal determination of S2 gradients, oral supplementation of saponins (200&#x202f;mg/day) or placebo regime was instigated for a period of 4 months. S2 gradients were re-evaluated at two and four months.<br><br>RESULTS: Basal S2 gradients of the AMD cohort were determined as 0.41&#x202f;&#xb1;&#x202f;0.24&#x202f;dB/min and those of the control subjects as 1.44&#x202f;&#xb1;&#x202f;0.1&#x202f;dB/min. After two months of the saponin treatment, AMD subjects showed improved S2 gradients of 0.92&#x202f;&#xb1;&#x202f;0.23&#x202f;dB/min (P&#x202f;<&#x202f;0.005) with a further increase to 1.35&#x202f;&#xb1;&#x202f;0.19&#x202f;dB/min at four months (P&#x202f;<&#x202f;0.01), the latter not being significantly different from control subjects. S2 gradients in placebo subjects were unaltered.<br><br>CONCLUSIONS: Oral supplementation with saponins results in reversing the reduced S2 gradients in AMD. This improvement in the transport properties of Bruch's is expected to slow, halt or reverse the progression of AMD.},
}
@article {pmid39818248,
year = {2025},
author = {Zou, W and Jiang, Q and Wang, Y and Wei, W and Sun, X and Basu, K and Chen, Q and Kotecha, A and Li, S and Liu, R and Patel, V and Chen, Y},
title = {Efficacy, durability and safety of faricimab for patients with neovascular age-related macular degeneration: 48-week results from the phase 3 LUCERNE China subpopulation.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {14},
number = {1},
pages = {100142},
doi = {10.1016/j.apjo.2025.100142},
pmid = {39818248},
issn = {2162-0989},
mesh = {Humans ; Male ; Female ; Double-Blind Method ; *Visual Acuity ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Aged ; Middle Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; China ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Tomography, Optical Coherence ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Time Factors ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To evaluate the efficacy, durability and safety of intravitreal faricimab versus aflibercept over 48 weeks in patients with neovascular age-related macular degeneration (nAMD) from the LUCERNE China subpopulation.<br><br>DESIGN: LUCERNE (NCT03823300) was a phase 3 global, double-masked, active comparator-controlled trial. The China subpopulation comprised patients from mainland China, Taiwan and Hong Kong.<br><br>METHODS: Treatment-na&#xef;ve patients aged &#x2265;50 years with nAMD were randomized 1:1 to receive faricimab 6.0&#x202f;mg up to every 16 weeks (Q16W) based on prespecified disease criteria after four initial Q4W doses or aflibercept 2.0&#x202f;mg Q8W after three initial Q4W doses. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) averaged over weeks 40 to 48. Anatomical, durability and safety outcomes were also evaluated.<br><br>RESULTS: The China subpopulation comprised 119 patients (faricimab: n = 59, aflibercept: n = 60). At weeks 40 to 48, adjusted mean (95% confidence interval [CI]) BCVA letter gains from baseline were +9.7 (7.4 to 12.0) and +9.8 (7.5 to 12.1) with faricimab and aflibercept, respectively. Central subfield thickness was reduced from baseline by weeks 40 to 48 in both arms, with an adjusted mean (95% CI) change of -145.4&#x202f;&#xb5;m (-156.2 to -134.6) and -156.5&#x202f;&#xb5;m (-167.3 to -145.7) for faricimab and aflibercept, respectively. By week 48, 87.3% of the patients were on extended &#x2265;Q12W faricimab dosing. Faricimab was well tolerated with no new safety signals.<br><br>CONCLUSIONS: Faricimab up to Q16W showed durable efficacy in the LUCERNE China subpopulation, consistent with global findings. Faricimab may reduce treatment burden for patients with nAMD in China, without compromising efficacy.},
}
@article {pmid39817215,
year = {2025},
author = {Liu, SQ and Wang, D and Tang, CC},
title = {Association between age at diagnosis of diabetes and ocular disease: Insights from a recent article.},
journal = {World journal of diabetes},
volume = {16},
number = {1},
pages = {94846},
pmid = {39817215},
issn = {1948-9358},
abstract = {In this article, we discuss Ye et al's recent article on the association between age at diabetes diagnosis and subsequent risk of age-related ocular diseases. The study, which utilized United Kingdom Biobank data, highlighted a strong link between early diabetes onset and major eye conditions, such as cataracts, glaucoma, age-related macular degeneration, and vision loss, independent of glycemic control and disease duration. This finding challenges the previous belief that diabetic eye disease primarily correlates with hyperglycemia. As lifestyles evolve and the age of diabetes diagnosis decreases, understanding this relationship may reveal the complex pathogenesis underlying diabetes-related complications. This editorial summarizes potential mechanisms connecting the age of diabetes onset with four types of ocular diseases, emphasizing the significance of early diagnosis.},
}
@article {pmid39815459,
year = {2025},
author = {Zhu, TC and Pogue, BW and Dimofte, A and Finlay, JC and Lilge, L and Sunar, U and Simone, CB and van Veen, RLP},
title = {AAPM Task Group Report 274: Fluence rate dosimetry for photodynamic therapy (PDT).},
journal = {Medical physics},
volume = {52},
number = {3},
pages = {1354-1371},
pmid = {39815459},
issn = {2473-4209},
support = {R01 EB028778/EB/NIBIB NIH HHS/United States ; R01 EB032821/EB/NIBIB NIH HHS/United States ; R21 EB026778/EB/NIBIB NIH HHS/United States ; },
mesh = {*Photochemotherapy/methods ; *Radiometry/methods/instrumentation/standards ; Humans ; },
abstract = {Photodynamic therapy (PDT) is a treatment modality clinically approved for several oncologic indications, including esophageal and endobronchial cancers, precancerous conditions including Barrett's esophagus and actinic keratosis, and benign conditions like age-related macular degeneration. While it is currently clinically underused, PDT is an area of significant research interest. Because PDT relies on the absorption of light energy by intrinsic or administered absorbers, the dosimetric quantity of interest is the absorbed energy per unit mass of tissue, proportional to the fluence rate of light in tissue. It has been demonstrated that the fluence rate at the tissue surface may differ significantly from the incident irradiance of light because of multiple scattering and absorption, both of which may vary among patients and tissue types. This report will review the current state-of-the-art fluence rate dosimetry technology. It will describe the two types of detectors currently available for fluence rate measurement, scattering-tip and fluorescence-based detectors, and review their principles of operation. The report will recommend strategies to establish calibration and quality assurance procedures for clinical fluence rate dosimetry equipment, and it will establish guidelines for clinical implementation of fluence rate dosimetry.},
}
@article {pmid39813058,
year = {2025},
author = {},
title = {Erratum in: Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {1},
pages = {37},
doi = {10.1167/iovs.66.1.37},
pmid = {39813058},
issn = {1552-5783},
}
@article {pmid39812800,
year = {2025},
author = {Zimmermann, JA and Irlenbusch, L and Hansen, U and Himmler, M and Zeng, C and Eter, N and Fuchsluger, T and Heiduschka, P},
title = {Long-term cultivation of retinal pigment epithelium cells on nanofiber scaffolds.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {5},
pages = {1327-1336},
pmid = {39812800},
issn = {1435-702X},
mesh = {*Retinal Pigment Epithelium/metabolism/ultrastructure/cytology ; Animals ; *Nanofibers ; *Tissue Scaffolds ; Swine ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Microscopy, Electron, Transmission ; *Cell Culture Techniques/methods ; Immunohistochemistry ; Cytokines/metabolism ; Time Factors ; *Tissue Engineering/methods ; Polyesters ; },
abstract = {PURPOSE: The retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age-related macular degeneration (AMD) and other retinal degenerative diseases. The introduction of healthy RPE cell cultures into the subretinal space offers a potential treatment strategy. The aim of this study was the long-term culture and characterisation of RPE cells on nanofiber scaffolds.<br><br>METHODS: Nanofiber scaffolds consisting of polycaprolactone (PCL) and collagen were prepared by electrospinning. Porcine RPE cell cultures were maintained on PCL scaffolds, PCL-collagen scaffolds, and controls at the bottom of 24-well plates. Cell culture analysis was performed by immunohistochemistry, while the release of inflammatory cytokines IL-6, IL-8, TNF-&#x3b1;, and PDGF-&#x3b2; was measured by ELISA and multiplex assays. Ultrastructural features were examined by transmission electron microscopy.<br><br>RESULTS: The observation period averaged 42.7 weeks for controls, 38.7 weeks for PCL scaffold cultures, and 36.1 weeks for PCL-collagen scaffold cultures, with cell number and morphology remaining stable. TNF-&#x3b1; levels in the supernatants were minimal, IL-6 levels were consistently low, and IL-8 levels decreased from initially high to lower levels over time.<br><br>CONCLUSION: RPE cells were stably cultured on nanofiber scaffolds for extended periods of time. The long-term physiological properties of RPE cells, including phagocytic ability and visual cycle enzyme activity, need to be further investigated before clinical application. In addition, controlling the expression of inflammatory mediators is a major challenge. Despite these hurdles, overcoming them is critical given the increasing prevalence of retinal degenerative diseases.},
}
@article {pmid39811964,
year = {2025},
author = {Pennisi, F and Gentile, L and Borlini, S and Gianfredi, V and Signorelli, C},
title = {Direct and indirect healthcare costs of ocular diseases in Italy: a literature review on glaucoma, diabetic retinopathy, and macular degeneration.},
journal = {Annali di igiene : medicina preventiva e di comunita},
volume = {37},
number = {4},
pages = {532-555},
doi = {10.7416/ai.2025.2676},
pmid = {39811964},
issn = {3035-5559},
mesh = {Humans ; Italy/epidemiology ; *Diabetic Retinopathy/economics/therapy/epidemiology ; *Macular Degeneration/economics/therapy/epidemiology ; *Glaucoma/economics/therapy/epidemiology ; *Health Care Costs/statistics &amp; numerical data ; Cost of Illness ; },
abstract = {BACKGROUND: Glaucoma, diabetic retinopathy, and age-related macular degeneration impose substantial economic burdens on healthcare systems due to their high prevalence and chronic nature. Nevertheless, comprehensive Italian data is limited. This study aims to collect Italian evidence on the economic impact of these conditions to support more effective healthcare planning.<br><br>STUDY DESIGN: Systematic review.<br><br>METHODS: A systematic literature search was conducted in accordance with PRISMA guidelines across PubMed, Scopus, Web of Science, and EMBASE databases. Studies reporting cost evaluations of managing glaucoma, diabetic retinopathy, and age-related macular degeneration in Italy were included. Direct, indirect and non-medical costs were considered.<br><br>RESULTS: The review included 23 studies exhibiting considerable heterogeneity in timeframes, regions, and economic evaluation approaches. For glaucoma, annual direct costs ranged from &#x20ac;788.70 for early-stage cases to &#x20ac;8,368.51 for advanced cases requiring surgery. Annual costs associated with diabetic retinopathy ranged from &#x20ac;4,050 to &#x20ac;5,799 per patient, depending on disease severity and treatment approach. The financial burden of age-related macular degeneration varied considerably, with costs ranging from &#x20ac;1,399.20 for early-stage cases to &#x20ac;3,973.30 for advanced stages. Although non-medical and indirect costs, such as lost productivity and caregiving expenses were less frequently assessed, they represented a significant contributor to the overall financial burden.<br><br>CONCLUSIONS: This study highlights the substantial economic burden ocular diseases place on the Italian healthcare system. Early intervention and preventive strategies could reduce the long-term costs of managing diabetic retinopathy and age-related macular degeneration. Further research into indirect costs and cost-effective interventions is necessary to support more efficient healthcare resource allocation.},
}
@article {pmid39811265,
year = {2025},
author = {Schneider, EW and Heier, JS and Holekamp, NM and Busquets, MA and Wagner, AL and Mukkamala, SK and Riemann, CD and Lee, SY and Joondeph, BC and Houston, SS and Nahen, K and Mohan, N and Benyamini, G},
title = {Pivotal Trial Toward Effectiveness of Self-administered OCT in Neovascular Age-related Macular Degeneration. Report 2-Artificial Intelligence Analytics.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100662},
pmid = {39811265},
issn = {2666-9145},
abstract = {PURPOSE: To validate the performance of the Notal OCT Analyzer (NOA) in processing self-administered OCT images from an OCT system designed for home use (home OCT [HOCT]) as part of a pivotal study aimed at achieving de novo United States Food and Drug Admininstration marketing authorization.<br><br>DESIGN: A prospective quantitative cross-sectional artificial intelligence study.<br><br>PARTICIPANTS: The study enrolled adults aged &#x2265;55 years diagnosed with neovascular age-related macular degeneration (nAMD) in &#x2265;1 eligible eye with a best-corrected visual acuity of 20/320 or better.<br><br>METHODS: Participants self-imaged 4 times on each of 2 HOCT devices and once with an in-office OCT (IO-OCT) device during a single visit. Scans were segmented by the NOA and human graders at a certified reading center (RC).<br><br>MAIN OUTCOME MEASURES: Intradevice and interdevice repeatability and reproducibility of total retinal hyporeflective (TRO) volume estimation by the NOA on HOCT-acquired images as compared with that of RC graders on IO-OCT-acquired images. Additionally, to assess the performance of the NOA in segmentation of TRO over multiple B-scans as compared with RC graders.<br><br>RESULTS: Self-imaging was performed successfully by 387 participants in 2451 of 2616 attempts (93.7%). For repeatability, the coefficient of variance for NOA was 11.1% for eyes with >10 volume units of TRO imaged with HOCT compared with 16.4% for RC graders segmenting IO-OCT images. The median DICE similarity coefficients for segmentation of TRO by NOA vs. Grader 1, Grader 2, and Grader 3; Grader 1 vs. Grader 2 and Grader 3; and Grader 2 vs. Grader 3 were 0.68, 0.68, 0.61, 0.72, 0.63, 0.70, respectively.<br><br>CONCLUSIONS: The performance of NOA supports the intended use of the system as a tool to monitor TRO at home between routine clinical visits in support of the management of nAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39808276,
year = {2025},
author = {Bourdin, A and Cohen, SY and Nghiem-Buffet, S and Smadja, J and Paques, M and Fajnkuchen, F and Mrejen, S},
title = {Vitritis following intravitreal faricimab: a retrospective monocentric analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {4},
pages = {965-972},
pmid = {39808276},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; Aged ; *Vitreous Body/pathology/drug effects ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Visual Acuity ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Incidence ; Tomography, Optical Coherence ; Aged, 80 and over ; Antibodies, Bispecific ; },
abstract = {PURPOSE: Intravitreal injections of anti-VEGF agents are considered as safe, with a very low rate of intraocular inflammations (IOI). Faricimab is a novel intravitreal bispecific antibody targeting both VEGF-A and angiopoietin-Tie2 independently. Despite a safe profile in randomized clinical trials, several real-life studies have reported cases of IOI. The aim of this monocentric study was to report the incidence and clinical course of intraocular inflammation following intravitreal faricimab injections.<br><br>METHODS: A retrospective analysis was performed in our tertiary care center, based on the observation of cases between December 1, 2023 and April 30, 2024. The incidence of intraocular inflammation occurring following faricimab injections compared to other anti-VEGF agents and dexamethasone implants was assessed over the study period.<br><br>RESULTS: Intraocular inflammation was observed in 11 eyes of seven patients, and presented as isolated, painless anterior uveitis with retrocorneal precipitates in three cases and vitritis associated with anterior uveitis in eight cases. The pattern of vitritis appeared distinctive, characterized by dense, grayish vitreous bands observed mainly in the peripheral fundus. The inflammatory phase persisted for 2-10 weeks, and regressed with steroid treatment. The overall incidence of IOI with faricimab was 0.87% (11 out of 1,271 injections), with vitritis specifically observed in 0.63% of cases (8 out of 1,271 injections). In contrast, of the 3,728 injections of other anti-VEGF agents administered (including 1,765 injections of aflibercept, 1,952 injections of ranibizumab) and 43 injections of dexamethasone implants, no cases of intraocular inflammation were reported.<br><br>CONCLUSIONS: Our initial experience with faricimab indicates a potentially higher risk of intraocular inflammation, including a distinctive pattern of vitritis, compared to aflibercept and ranibizumab. The benefit/risk ratio should be carefully assessed, particularly in patients with monocular vision or who require simultaneous bilateral injections.},
}
@article {pmid39807649,
year = {2025},
author = {Liao, J and Zhao, L and Chen, H and Zhao, C and Chen, S and Guo, X and Wang, F and Liu, X and Zhang, X},
title = {A Bifunctional Peptide with Penetration Ability for Treating Retinal Angiogenesis via Eye Drops.},
journal = {Molecular pharmaceutics},
volume = {22},
number = {2},
pages = {708-720},
doi = {10.1021/acs.molpharmaceut.4c00683},
pmid = {39807649},
issn = {1543-8392},
mesh = {Animals ; *Retinal Neovascularization/drug therapy/metabolism ; Rats ; Zebrafish ; *Angiogenesis Inhibitors/pharmacology/administration &amp; dosage ; *Ophthalmic Solutions/administration &amp; dosage/chemistry ; *Peptides/chemistry/pharmacology/administration &amp; dosage ; Endothelial Cells/drug effects ; Humans ; Cell Proliferation/drug effects ; Vascular Endothelial Growth Factor Receptor-2/metabolism/antagonists &amp; inhibitors ; Blood-Retinal Barrier/drug effects/metabolism ; Retina/drug effects/metabolism ; Cell Movement/drug effects ; Disease Models, Animal ; Angiogenesis ; },
abstract = {Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases. RP7 is an NRP-1 targeting peptide that blocks vascular endothelial growth factor receptor-2 (VEGFR-2) signaling and inhibits angiogenesis, while Tat facilitates the delivery of various cargoes across biological barriers, such as the blood-retina barrier. By combining these attributes, Tat-C-RP7 is anticipated to traverse ocular barriers via ocular topical administration and exert its antiangiogenic effects in the ocular posterior segment. Experimental results demonstrated that Tat-C-RP7 significantly inhibited the proliferation and migration of rat retinal microvascular endothelial cells and effectively reduced tubule formation in vitro. Its antiangiogenic activity was confirmed in zebrafish. The outstanding penetrative capabilities of FITC-labeled Tat-C-RP7 have been validated through cell uptake assays, in vitro cell barrier models, ex-vivo ocular tissues, and in vivo studies. Besides, the half-life of Tat-C-RP7 was longer than that of RP7. In an oxygen-induced retinopathy model, Tat-C-RP7 was shown to reduce the area of angiogenesis following ocular administration. Additionally, it produced no irritating effects on the eyes of rabbits. Overall, Tat-C-RP7 demonstrates excellent ocular penetrability and antiangiogenic effects and represents a promising therapeutic option for treating retinal neovascularization diseases.},
}
@article {pmid39807268,
year = {2025},
author = {López Estrada, D and Chang, WT and Heinrich, M},
title = {From "traditional" to modern medicine: A medical and historical analysis of Tagetes erecta L. (Cempasúchil).},
journal = {Journal of traditional and complementary medicine},
volume = {15},
number = {1},
pages = {6-14},
pmid = {39807268},
issn = {2225-4110},
abstract = {The medicinal value of herbal products is often rooted in their "traditional" use, recontextualized by modern biomedical research granting them certain medical uses. Tagetes erecta L. (Asteraceae), native to Mexico, exemplifies such historical developments of a species that played a key role in developing a major pharmacologically active compound - lutein. T. erecta (Cempasúchil in Nahuatl) has held ritual and medicinal importance in Mesoamerica and was associated with the rain god Tláloc. The species' historical use spans ancient texts with varied medicinal applications, including treating cold-related ailments and promoting menstruation and urination. However, the Spanish conquest redefined it culturally, medicinally, and religiously, mainly as an ornamental flower. The discovery of lutein in T. erecta marked a significant shift, emphasizing its role in macular health and preventing aging-related macular degeneration. Clinically, lutein trials reveal cognitive, visual, cardiovascular, and systemic health enhancements, substantiating its potential therapeutic benefits. Pharmacologically, it demonstrates significant anti-inflammatory, antiparasitic, and anticancer properties. Today, T. erecta is recognized globally for its rich carotenoid content. This multifunctional metabolite is also used in poultry feed and health supplements. In contemporary culture, cempasúchil, also known as the "flower of the dead," has been adapted for ornamental, medicinal, ceremonial, and industrial uses. However, its traditional medicinal uses in pre-Conquest Mexico remain largely unexplored, with its current applications influenced by global research. T. erecta's evolution beyond traditional medical and ritual uses in Mesoamerica demonstrates the dynamic development of a medicinal plant's role in medicine, as well as a range of other spheres of daily life.},
}
@article {pmid39807175,
year = {2025},
author = {Zeng, L and Zhang, J and Chen, W and Ding, Y},
title = {tdCoxSNN: Time-dependent Cox survival neural network for continuous-time dynamic prediction.},
journal = {Journal of the Royal Statistical Society. Series C, Applied statistics},
volume = {74},
number = {1},
pages = {187-203},
pmid = {39807175},
issn = {0035-9254},
support = {R21 EY030488/EY/NEI NIH HHS/United States ; S10 OD028483/OD/NIH HHS/United States ; },
abstract = {The aim of dynamic prediction is to provide individualized risk predictions over time, which are updated as new data become available. In pursuit of constructing a dynamic prediction model for a progressive eye disorder, age-related macular degeneration (AMD), we propose a time-dependent Cox survival neural network (tdCoxSNN) to predict its progression using longitudinal fundus images. tdCoxSNN builds upon the time-dependent Cox model by utilizing a neural network to capture the nonlinear effect of time-dependent covariates on the survival outcome. Moreover, by concurrently integrating a convolutional neural network with the survival network, tdCoxSNN can directly take longitudinal images as input. We evaluate and compare our proposed method with joint modelling and landmarking approaches through extensive simulations. We applied the proposed approach to two real datasets. One is a large AMD study, the Age-Related Eye Disease Study, in which more than 50,000 fundus images were captured over a period of 12 years for more than 4,000 participants. Another is a public dataset of the primary biliary cirrhosis disease, where multiple laboratory tests were longitudinally collected to predict the time-to-liver transplant. Our approach demonstrates commendable predictive performance in both simulation studies and the analysis of the two real datasets.},
}
@article {pmid39807091,
year = {2025},
author = {Rush, RB and Klein, W and Rush, SW and Reinauer, R},
title = {One-Year Outcomes in Subjects Developing Macular Neovascularization While Undergoing Avacincaptad Pegol Therapy for Geographic Atrophy.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {111-118},
pmid = {39807091},
issn = {1177-5467},
abstract = {PURPOSE: To assess the 12-month outcomes in subjects developing macular neovascularization (MNV) during intravitreal avacincaptad pegol (IVA) treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>METHODS: This research was conducted as a case-controlled, retrospective study of AMD subjects undergoing IVA treatment for GA from two private practice institutions. Subjects were divided into 1) a Study Group of patients who developed MNV and then underwent anti-vascular endothelial growth factor (VEGF) therapy during the study period, and 2) a Control Group of patients who were complication-free during the study period. Both cohorts had a baseline Snellen visual acuity of &#x2265; 20/200, a baseline GA total area of &#x2265; 1 mm[2]and &#x2264; 17.5 mm[2], and 12 months of follow-up after initiation of IVA for GA.<br><br>RESULTS: There were 56 patients analyzed. There were no significant differences in baseline features between cohorts. The Study Group had a greater decrease in visual acuity [-0.22 logMAR (-0.27 to -0.17) versus -0.06 logMAR (-0.12 to 0.00); p=<0.0001], and greater GA total lesion growth [1.78 mm[2] (1.53-2.03) versus 0.78 mm[2] (0.54-1.02); p=<0.0001] during the 12-month study period compared to the Control Group.<br><br>CONCLUSION: Patients developing MNV while undergoing IVA treatment for GA secondary to AMD have worse clinical outcomes despite undergoing anti-VEGF therapy compared to patients who were complication-free at 12-months. This highlights the seriousness of MNV in this patient population and may help specialists counsel patients when considering treatment for GA secondary to AMD.},
}
@article {pmid39806623,
year = {2024},
author = {Ho, RTH and Cheong, AMY and Wan, AHY and Lo, TLT and Fong, TCT and Chan, CKP and Li, Q and Chan, WC},
title = {Protocol for a mixed-methods randomised controlled trial evaluating the psychosocial effects of an expressive arts-based intervention on adults with age-related macular degeneration.},
journal = {BMJ open},
volume = {14},
number = {12},
pages = {e088311},
pmid = {39806623},
issn = {2044-6055},
mesh = {Humans ; *Macular Degeneration/psychology/therapy ; *Art Therapy/methods ; Randomized Controlled Trials as Topic ; Aged ; Female ; Male ; Quality of Life ; Middle Aged ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a prevalent eye disease among middle-aged and older adults. AMD leaves the patient with irreversible deteriorating vision, which profoundly impacts their daily lives and psychosocial well-being. Given the limited studies addressing the psychosocial needs of adults with AMD and, in particular, using an expressive arts-based intervention (EXABI) as an intervention, this study aims to investigate the effectiveness of such an intervention in enhancing the psychosocial well-being of adults with AMD.<br><br>METHODS AND ANALYSIS: This study will employ a mixed-methods randomised controlled trial design. One hundred fifty-four participants with AMD will be recruited and randomised into either the EXABI or treatment-as-usual waitlist control group. Participants will respond to a battery of measurements regarding their psychosocial condition at four time points: baseline (T0), 2 months after baseline (postintervention, T1), 5 months after baseline (T2) and 8 months after baseline (T3). A subgroup of participants will also share their experiences through in-depth interviews at T1 and T3 to help further understand the mechanism and effect of the intervention. Quantitative data will be analysed by mixed-effects models and path analysis, whereas qualitative data will be analysed by adopting the thematic analysis approach. The two sets of data will be integrated to provide a comprehensive view of the effectiveness and mechanisms of the intervention.<br><br>ETHICS AND DISSEMINATION: This study has obtained ethical approval from the Human Research Ethics Committee of the University of Hong Kong (Ref. no.: EA210606). All research procedures will be conducted upon receiving signed written consent forms from participants. The findings of the study will also be presented at international conferences and published in peer-reviewed academic journals.<br><br>TRIAL REGISTRATION NUMBER: NCT05675150, prospectively registered.},
}
@article {pmid39805963,
year = {2025},
author = {Adamo, GG and Pellegrini, M and Nasini, F and Talli, PM and Sarti, L and Perri, P and Parmeggiani, F and Mura, M},
title = {Anatomical and functional results of patients with late-stage age-related macular degeneration 6 months after smaller-incision new-generation implantable miniature telescope (SING IMT™) implantation.},
journal = {Eye (London, England)},
volume = {39},
number = {3},
pages = {544-547},
pmid = {39805963},
issn = {1476-5454},
mesh = {Humans ; Visual Acuity/physiology ; Male ; Female ; Retrospective Studies ; Aged ; Aged, 80 and over ; *Macular Degeneration/physiopathology/surgery ; *Prosthesis Implantation ; Phacoemulsification ; Follow-Up Studies ; Middle Aged ; Treatment Outcome ; Corneal Endothelial Cell Loss ; Postoperative Complications ; },
abstract = {OBJECTIVES: The aim of the study was to evaluate anatomical and functional outcomes of the Smaller-Incision New Generation Implantable Miniature Telescope (SING IMT™) in patients with bilateral advanced age-related macular degeneration (AMD).<br><br>METHODS: This non-comparative retrospective single-surgeon interventional case series included patients with bilateral late-stage AMD who underwent cataract surgery and SING IMT&#x2122; implantation at the Sant'Anna University Hospital, University of Ferrara, Italy. The main outcome measures included corrected distance (CDVA) and near visual acuity (CNVA), endothelial cell loss (ECL), and incidence of complications.<br><br>RESULTS: 11 eyes of 11 patients were included. The mean follow-up duration was 6.5&#x2009;&#xb1;&#x2009;2.4 months. After surgery, CDVA significantly improved (from 17.00&#x2009;&#xb1;&#x2009;9.74 to 26.00&#x2009;&#xb1;&#x2009;8.53) letters (P&#x2009;=&#x2009;0.008). Significant improvement of CNVA was also observed (from 12.27&#x2009;&#xb1;&#x2009;4.36 to 8&#x2009;&#xb1;&#x2009;2.61 Jaeger levels; P&#x2009;=&#x2009;0.004). Mean ECL was 4.8&#x2009;&#xb1;&#x2009;5.5% at 3 months. No intraoperative complications were observed, while postoperative complications included iris incarceration (9.1%), pigment deposition on the device (9.1%), and transient corneal oedema (27.3%). Nevertheless, 10 of 11 patients (90.9%) began to complain of blurred or hazy vision within 3 months of surgery. The device was ultimately explanted in 3 patients (27.3%) because of this symptom.<br><br>CONCLUSIONS: Although SING IMT&#x2122; implantation is associated with promising objective results, unexplained blurred or hazy vision represents common postoperative complaints which may lead to patient dissatisfaction. Further studies including patient-reported outcomes are warranted to evaluate the effect of the intervention on patients' visual function and quality of life.},
}
@article {pmid39805961,
year = {2025},
author = {Heier, JS and Zhang, X and Reed, K and Berliner, A and Leal, S},
title = {Infographic: Efficacy and safety of high-dose Intravitreal aflibercept 8 mg in patients with neovascular age-related macular degeneration: week 48 results from the phase 3 PULSAR trial.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41433-024-03543-x},
pmid = {39805961},
issn = {1476-5454},
support = {N/A//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; N/A//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; N/A//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; N/A//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; N/A//Regeneron Pharmaceuticals (Regeneron Pharmaceuticals, Inc.)/ ; },
}
@article {pmid39805344,
year = {2025},
author = {Szabó, V and Varsányi, B and Barboni, M and Takács, &#xc1; and Knézy, K and Molnár, MJ and Nagy, ZZ and György, B and Rivolta, C},
title = {Insights into eye genetics and recent advances in ocular gene therapy.},
journal = {Molecular and cellular probes},
volume = {79},
number = {},
pages = {102008},
doi = {10.1016/j.mcp.2025.102008},
pmid = {39805344},
issn = {1096-1194},
mesh = {Humans ; *Genetic Therapy/methods ; Animals ; *Eye Diseases/therapy/genetics ; *Eye/metabolism ; },
abstract = {The rapid advancements in the field of genetics have significantly propelled the development of gene therapies, paving the way for innovative treatments of various hereditary disorders. This review focuses on the genetics of ophthalmologic conditions, highlighting the currently approved ophthalmic gene therapy and exploring emerging therapeutic strategies under development. Inherited retinal dystrophies represent a heterogeneous group of genetic disorders that manifest across a broad spectrum from infancy to late middle age. Key clinical features include nyctalopia (night blindness), constriction of the visual field, impairments in color perception, reduced central visual acuity, and rapid eye movements. Recent technological advancements, such as multimodal imaging, psychophysical assessments, and electrophysiological testing, have greatly enhanced our ability to understand disease progression and establish genotype-phenotype correlations. Additionally, the integration of molecular diagnostics into clinical practice is revolutionizing patient stratification and the design of targeted interventions, underscoring the transformative potential of personalized medicine in ophthalmology. The review also covers the challenges and opportunities in developing gene therapies for other ophthalmic conditions, such as age-related macular degeneration and optic neuropathies. We discuss the viral and non-viral vector systems used in ocular gene therapy, highlighting their advantages and limitations. Additionally, we explore the potential of emerging technologies like CRISPR/Cas9 in treating genetic eye diseases. We briefly address the regulatory landscape, concerns, challenges, and future directions of gene therapy in ophthalmology. We emphasize the need for long-term safety and efficacy data as these innovative treatments move from bench to bedside.},
}
@article {pmid39805004,
year = {2025},
author = {},
title = {Correction to "Red Light-Triggered Anti-Angiogenic and Photodynamic Combination Therapy of Age-Related Macular Degeneration".},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {6},
pages = {e2416442},
doi = {10.1002/advs.202416442},
pmid = {39805004},
issn = {2198-3844},
}
@article {pmid39804630,
year = {2025},
author = {Liu, H and Zhang, X and Wang, Q and Li, B and Bian, B and Liu, Y},
title = {A Comprehensive Analysis of Sex-Biased Gene Expression in the Aging Human Retina Through a Combination of Single-Cell and Bulk RNA Sequencing.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {1},
pages = {28},
pmid = {39804630},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; *Aging/genetics ; Single-Cell Analysis ; *Retina/metabolism ; Sequence Analysis, RNA/methods ; Aged ; Middle Aged ; *Gene Expression Regulation/physiology ; Animals ; Mice ; Aged, 80 and over ; Sex Factors ; Adult ; },
abstract = {PURPOSE: Previous studies have reported divergent sexual responses to aging; however, specific variations in gene expression between aging males and females and their potential association with age-related retinal diseases remain unclear. This study collected data from public databases and developed a comprehensive comparison of retina between aging females and males.<br><br>METHODS: Single-cell RNA (scRNA) and bulk RNA sequencing data of the aging retina from females and males in public databases were utilized for integrated analysis to investigate sex-biased expression in retina. Additionally, in vitro experiments were conducted on individuals with retinitis pigmentosa (RP) to validate the sex difference in degenerative retina.<br><br>RESULTS: Bulk RNA analysis revealed sex-biased expression of specific genes in retina of aging individuals, with immune pathway-related genes exhibiting higher expression in females compared to males. The scRNA analysis demonstrated that sex-biased gene expression was cell-type specific in aging retina. Furthermore, susceptibility genes for age-related macular degeneration and RP exhibited variation across different cell types and sexes. Cell-to-cell communication unveiled an increased interaction associated with TGFB1, CCL7, and VEGFA in M&#xfc;ller glia, microglia, and astrocytes of female retina. Notably, we observed female-biased chemokine expression in microglia contributing to heightened susceptibility to immune inflammation in female retina. Finally, we confirmed a more pronounced inflammatory response during degeneration in female rd10 mouse retina compared to males.<br><br>CONCLUSIONS: This study provides a comprehensive comparison of retina between females and males in healthy aging human retina and highlights the significance of sex as an influential factor in retinal diseases.},
}
@article {pmid39803407,
year = {2024},
author = {Pan, Y and Iwata, T},
title = {Role of ARMS2/HTRA1 risk alleles in the pathogenesis of neovascular age-related macular degeneration.},
journal = {Taiwan journal of ophthalmology},
volume = {14},
number = {4},
pages = {531-539},
pmid = {39803407},
issn = {2211-5072},
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of severe irreversible blindness worldwide in the elderly population. AMD is a multifactorial disease mainly caused by advanced age, environmental factors, and genetic variations. Genome-wide association studies (GWAS) have strongly supported the link between ARMS2/HTRA1 locus on chromosome 10q26 and AMD development, encompassing multiple variants, rs10490924 (c.205G > T, p.A69S in ARMS2), insertion/deletion (del443/ins54 in ARMS2), and rs11200638 (in HTRA1 promoter region). In this comprehensive review, we provide an overview of the role played by ARMS2/HTRA1 risk alleles in neovascular AMD pathogenesis, covering GWAS, in vitro studies, and animal models, shedding light on their underlying molecular genetic mechanisms. Further extensive research is also imperative, including confirmation of these findings, identifying novel treatment targets, and advancing primary and secondary prevention strategies for AMD.},
}
@article {pmid39803399,
year = {2024},
author = {Ong, CJT and Cheung, CMG},
title = {An atypical case of retinal pigment epithelium tear with remodeling and visual preservation.},
journal = {Taiwan journal of ophthalmology},
volume = {14},
number = {4},
pages = {614-618},
pmid = {39803399},
issn = {2211-5072},
abstract = {This report describes a patient with polypoidal choroidal vasculopathy (PCV) with fovea-involving retinal pigment epithelium (RPE) tear that showed tissue remodeling with a good visual outcome. Imaging over the patient's clinical course from 2019 was reviewed. A 74-year-old female presented with left submacular hemorrhage and a large multi-lobular pigment epithelial detachment. Left eye vision was 6/19 at the presentation. Indocyanine green angiography (ICGA) revealed underlying PCV. One month after initiation of intravitreal aflibercept (IVA, Bayer), she developed fresh subretinal hemorrhage. An RPE tear of 1 disc area in size, centered over the fovea was diagnosed. The torn RPE edge was scrolled up temporal to the fovea on spectral-domain optical coherence tomography (SD-OCT), with hypertransmission into the choroid observed over the area of RPE loss. Left eye vision after the RPE tear was 6/15. Over the next 2 months, the subretinal hemorrhage resolved following further IVA. At month 3, fundus autofluorescence (FAF) demonstrated hypo-autofluorescence while fundus fluorescein angiography (FFA) and ICGA showed a window defect corresponding to the area of RPE tear. On SD-OCT, there was a faint hyper-reflective layer where one might expect the RPE layer to be. Serial SD-OCT scans over 5 years revealed increasing prominence of the hyperreflective layer between the ellipsoid zone and Bruch's membrane. FAF remained hypo-autofluorescent. At the last review, the patient retained 6/9 vision. We report a case of fovea-involving RPE tear documented with multimodal imaging with good visual outcome, which is atypical. Serial OCT suggests tissue remodeling may explain the functional preservation.},
}
@article {pmid39803396,
year = {2024},
author = {Cohn, AC and Guymer, RH},
title = {Current advances in multimodal imaging in geographic atrophy secondary to age-related macular degeneration: A review.},
journal = {Taiwan journal of ophthalmology},
volume = {14},
number = {4},
pages = {464-472},
pmid = {39803396},
issn = {2211-5072},
abstract = {As we move toward an era in which there will be treatment options for geographic atrophy (GA) secondary to age-related macular degeneration, the need to accurately understand and interpret multimodal imaging (MMI) for the condition is paramount. This review discusses the evolution of MMI in GA and how it has led to a greater understanding of different phenotypes and risk factors for progression. These advancements have allowed novel imaging biomarkers to be used as end points in large interventional studies exploring new therapies for GA treatment. Due to differences in drug approval timing, ophthalmologists in some jurisdictions are already treating patients with complement inhibiting intravitreal therapies and using MMI to guide management. Cementing knowledge of how GA appears on MMI and evolves over time will be vital for best practice as these interventions become more widely available.},
}
@article {pmid39803039,
year = {2024},
author = {Bilal, A and Bilal, M and Usman, D and Elahi, A and Al-Bermani, A},
title = {A Tertiary Centre's Experience With Using Ranibizumab Biosimilar Compared to Aflibercept for Neovascular Age-Related Macular Degeneration: A Retrospective Study.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e75586},
pmid = {39803039},
issn = {2168-8184},
abstract = {Objective This study aims to evaluate the real-world efficacy of ranibizumab biosimilar (Ongavia), compared to aflibercept (Eylea), in the treatment of treatment-naïve neovascular age-related macular degeneration (nAMD) at a busy tertiary eye care centre. Methods A retrospective analysis of medical records from August 2022 to August 2024 was conducted, comparing treatment outcomes in treatment-naive nAMD patients who received either Ongavia or Eylea intravitreal anti-VEGF (vascular endothelial growth factor) injections under a treat-and-extend protocol. Initial and 12-month outcome measures post-treatment initiation were collected, including best-corrected visual acuity (BCVA), central retinal thickness (CRT), prescribed treatment intervals, actual injection frequency, and the average total number of injections per eye over 12 months. Results A total of 62 eyes met the inclusion criteria. Over 12 months of follow-up, patients receiving Eylea (n = 36) showed a significantly greater improvement in BCVA (7.08 ± 4.12), p = 0.018, compared to Ongavia (n = 26) (-1.9 ± 3.31). CRT reductions were also more substantial for Eylea (-116.21 µm ± 35.61 µm) than for Ongavia (-51.14 µm ± 22.21 µm), p = 0.002. The average number of injections was 6.55 for Ongavia and 5.75 for Eylea over the 12-month follow-up. Excluding the initial three loading doses, observed injection intervals averaged 9.49 weeks for Eylea and 8.17 weeks for Ongavia. Notably, for the total study period, 164 out of 171 (96%) Ongavia injections were prescribed at four-week intervals, compared to 110 out of 207 (53%) for Eylea. However, capacity constraints impacted adherence to prescribed dosing schedules, affecting efficacy. Conclusion Our study indicates reduced visual and morphological outcomes with Ongavia compared to Eylea in treating nAMD when monthly injections cannot be provided as prescribed. Given clinical capacity constraints, Eylea's greater potency and durability prove advantageous, allowing extended intervals and reducing the reliance on strict monthly dosing. This highlights the need for additional resources to support frequent biosimilar administration and ensure effective ranibizumab treatment. A comprehensive cost-benefit analysis is warranted to assess whether increased clinic capacity offsets Ongavia's lower per-injection cost, compared to Eylea.},
}
@article {pmid39800286,
year = {2025},
author = {Nag, TC},
title = {Accumulation of autophagosomes in aging human photoreceptor cell synapses.},
journal = {Experimental eye research},
volume = {251},
number = {},
pages = {110240},
doi = {10.1016/j.exer.2025.110240},
pmid = {39800286},
issn = {1096-0007},
mesh = {Humans ; Aged ; Aged, 80 and over ; Middle Aged ; *Aging/physiology ; *Autophagosomes/ultrastructure/metabolism ; Microscopy, Electron, Transmission ; *Synapses/ultrastructure ; Mitochondria/ultrastructure ; *Autophagy/physiology ; Female ; Male ; Retinal Cone Photoreceptor Cells/ultrastructure ; Retinal Rod Photoreceptor Cells/ultrastructure ; *Photoreceptor Cells, Vertebrate/ultrastructure ; Retinal Pigment Epithelium/ultrastructure ; Tissue Donors ; },
abstract = {Autophagy is common in the aging retinal pigment epithelium (RPE). A dysfunctional autophagy in aged RPE is implicated in the pathogenesis of age-related macular degeneration. Aging human retina accompanies degenerative changes in photoreceptor mitochondria. It is not known how the damaged mitochondria are handled by photoreceptor cells with aging. This study examined donor human retinas (age: 56-94 years; N = 12) by transmission electron microscopy to find mitochondrial dynamics and status of autophagy in macular photoreceptor cells. Observations were compared between the relatively lower age (56-78 years) and aged retinas (80-94 years). Mitochondrial fusion was predominant in photoreceptor inner segments (ellipsoids), but rarely seen in the synaptic terminals. Also, fusion became widespread with progressive aging in ellipsoids (12% and 21% between rods and cones at tenth decade, respectively). More importantly, it was found that the photoreceptor synaptic mitochondria altered significantly with aging (swelling and loss of cristae), compared to those in ellipsoids that became dark and condensed. The damaged synaptic mitochondria were sequestered inside autophagosomes, whose frequency was higher in aged photoreceptors, being 34% in cone and 24% in rod terminals, at tenth decade. However, autolysosomes/residual bodies were rare, and thus the aged photoreceptor synaptic terminals harboured many autophagosomes, the possible reasons for which are discussed. Such age-related altered mitochondrial population and defective autophagy in synaptic terminals may influence photoreceptor survival in late aging.},
}
@article {pmid39799346,
year = {2025},
author = {Xu, C and Wu, X},
title = {Association between four anthropometric indices with age-related Macular Degeneration from NHANES 2005-2008.},
journal = {Lipids in health and disease},
volume = {24},
number = {1},
pages = {11},
pmid = {39799346},
issn = {1476-511X},
mesh = {Humans ; *Macular Degeneration/epidemiology/pathology/physiopathology ; Female ; Male ; Middle Aged ; Aged ; Nutrition Surveys ; Waist Circumference ; Body Mass Index ; *Obesity/complications/epidemiology ; Anthropometry ; United States/epidemiology ; Risk Factors ; Odds Ratio ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) decrease vision and presents considerable challenges for both public health and clinical management strategies. Obesity is usually implicated with increased AMD, and body mass index (BMI) does not reflect body fat distribution. An array of studies has indicated a robust relationship between body fat distribution and obesity. This research is to evaluate the relationship between anthropometric measurements and AMD in the United States citizens in a cohort of patients.<br><br>METHODS: Our study included a cohort of 3,127 participants, all of whom were selected from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2008. Various anthropometric indices, including weight (WT), waist circumference (WC), Body Mass Index (BMI), waist-to-height ratio (WtHR), circularity index (CI), weight-adjusted waist circumference index (WWI), body roundness index (BRI), a body size index (ABSI), and visceral adiposity index (VAI), have been studied extensively within public health and nutrition to assess body fat distribution. Odds ratios (OR) for each anthropometric index, in relation to AMD and its different stages, were computed, adjusting for confounding variables. Smoothed curve fitting, coupled with weighted multivariable logistic regression analysis, was used to examine the impact of these anthropometric measures on the prevalence of AMD. Subgroup analyses were conducted according to gender, age, BMI, drinking, smoking, CVD, diabetes, hypertension, cataract operation, and glaucoma.<br><br>RESULTS: After adjusting for all variables, significant positive correlations were observed between WtHR (OR&#x2009;=&#x2009;1.237 (1.065-1.438)), BRI (OR&#x2009;=&#x2009;1.221 (1.058-1.410)), CI (OR&#x2009;=&#x2009;1.189 (1.039-1.362)), and WWI (OR&#x2009;=&#x2009;1.250 (1.095-1.425)) with AMD, particularly for early AMD. However, no significant effects of these indicators were observed in late AMD. CI exhibited a positive linear relationship with AMD. Two-segment linear regression modeling revealed positive nonlinear associations between WtHR, BRI, and WWI with AMD. The positive association was more pronounced with excessive alcohol consumption for WtHR, BRI, CI, and WWI (P for interaction&#x2009;=&#x2009;0.0033, 0.0021, 0.0194, and 0.0022, respectively). Additionally, WWI and CI exhibited stronger associations with AMD in females (P for interaction&#x2009;=&#x2009;0.0146 and 0.0117, respectively). Furthermore, WtHR was associated with AMD in non-smokers (P for interaction&#x2009;=&#x2009;0.0402).<br><br>CONCLUSION: This study confirmed a increased risk between four anthropometric measures, including WtHR, BRI, CI, and WWI, with AMD, especially early AMD. The findings suggest that these four anthropometric indices should be more broadly utilized to improve early AMD prevention and treatment strategies. Additionally, we found that the positive association between these four body measurement indices and AMD was more pronounced in individuals with high alcohol consumption.},
}
@article {pmid39799208,
year = {2025},
author = {Göller, S and Schmidberger, H},
title = {[Can stereotactic radiotherapy for neovascular age-related macular degeneration (STAR trial) enhance quality of life?].},
journal = {Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]},
volume = {201},
number = {3},
pages = {346-348},
pmid = {39799208},
issn = {1439-099X},
}
@article {pmid39799138,
year = {2025},
author = {Ziraldo, G and Cupini, S and Sesti, V and Delfino, E and Lanzani, G and Bertarelli, C and Benfenati, F and Di Marco, S},
title = {A membrane-targeted photoswitch restores physiological ON/OFF responses to light in the degenerate retina.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {600},
pmid = {39799138},
issn = {2041-1723},
support = {GMR22T2013//Fondazione Telethon (Telethon Foundation)/ ; GR-2021-12374630//Ministry of Health, Italy | Agenzia Italiana del Farmaco, Ministero della Salute (Italian Medicines Agency)/ ; 861423//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Sk&#x142;odowska-Curie Actions (H2020 Excellent Science - Marie Sk&#x142;odowska-Curie Actions)/ ; 2020XBFEMS//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca (Ministry of Education, University and Research)/ ; },
mesh = {Animals ; Mice ; Light ; Retinal Ganglion Cells/drug effects/radiation effects/physiology/metabolism ; Rats ; *Retinal Degeneration/physiopathology/genetics/drug therapy ; Optogenetics ; Disease Models, Animal ; Mice, Inbred C57BL ; *Retina/drug effects/radiation effects ; Male ; Retinitis Pigmentosa ; Female ; Humans ; Intravitreal Injections ; },
abstract = {The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies, such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, which is essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch that modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in mouse and rat genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances. Intravitreally injected Ziapin2 in fully blind rd10 mice restores light-driven behavior and optomotor reflexes. The results indicate that Ziapin2 is a promising molecule for reinstating physiological visual responses in the late stages of retinal degeneration.},
}
@article {pmid39799131,
year = {2025},
author = {Uozumi, H and Kawakami, S and Matsui, Y and Mori, S and Sato, A},
title = {Passion fruit seed extract protects hydrogen peroxide-induced cell damage in human retinal pigment epithelium ARPE-19 cells.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {1715},
pmid = {39799131},
issn = {2045-2322},
mesh = {Humans ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology/pathology ; *Plant Extracts/pharmacology/chemistry ; *Hydrogen Peroxide/toxicity ; Cell Survival/drug effects ; Oxidative Stress/drug effects ; Cell Line ; *Passiflora/chemistry ; *Seeds/chemistry ; Adenosine Triphosphate/metabolism ; Mitochondria/metabolism/drug effects ; Glycolysis/drug effects ; Stilbenes/pharmacology ; Protective Agents/pharmacology ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of vision loss among adults. We investigated the protective effects of passion fruit seed extract (PFSE) and its rich polyphenol piceatannol in an AMD cell model in which human retinal pigment epithelial ARPE-19 cells were exposed to hydrogen peroxide (H2O2). Using a cell viability WST-8 assay, we revealed that PFSE and piceatannol increased the cellular viability of ARPE-19 cells by 130% and 133%, respectively. Moreover, PFSE and piceatannol recovered the cell viability of ARPE-19 cells, which had decreased to 60% owing to H2O2-induced damage, to approximately 84% and 89%, respectively. In addition, we found that the treatment of ARPE-19 cells with H2O2 decreased the mitochondrial and glycolytic ATP production rate to approximately 54% that of healthy control ARPE-19 cells using a Seahorse extracellular flux analyzer. Furthermore, pretreatment with PFSE and piceatannol restored the oxidative stress-induced decrease in the mitochondrial and glycolytic ATP production rate to approximately 97% and 82%, respectively. These results indicated the cytoprotective effects of PFSE and piceatannol against oxidative stress in human ARPE-19 cells by resolving the dysfunction of mitochondrial and glycolytic energy metabolism.},
}
@article {pmid39797140,
year = {2024},
author = {Gilligan, AK and Ramsey, DJ},
title = {Beyond Longer Intervals: Advocating for Regular Treatment of Neovascular AMD.},
journal = {Journal of clinical medicine},
volume = {14},
number = {1},
pages = {},
pmid = {39797140},
issn = {2077-0383},
abstract = {Personalizing the management of neovascular age-related macular degeneration (nAMD) poses significant challenges for practicing retina specialists and their patients. This commentary addresses some of these complexities, particularly those that arise in the context of an expanding array of intravitreal agents targeting vascular endothelial growth factor (VEGF) and related retinal disease targets. Many of these newer agents approved by the Food and Drug Administration (FDA) for the treatment of nAMD have labeling that indicates that they can provide non-inferior visual outcomes when compared head-to-head with previously available treatments and can be used at significantly extended dosing intervals in some patients. It can be difficult to know if patients should be transitioned to these agents, especially those who are doing well on existing therapies. Although offering extended intervals may be appropriate for some patients with excellent disease control, retina specialists know that undertreatment risks the loss of visual acuity (VA). It can also be challenging for clinicians to interpret the results delivered by clinical trial treatment protocols compared with what is likely to occur in real-world office settings. Many retina specialists use less liberal treatment paradigms than employed in clinical study protocols and consequently many patients experience shorter injection intervals. Since VA is most closely linked to quality of life, it should be prioritized compared with other endpoints. The authors advocate for maintaining consistent treatment schedules dictated by disease control instead of switching therapies even in the presence of small amounts of macular fluid that may occur with longer injection intervals.},
}
@article {pmid39794542,
year = {2025},
author = {Viggiano, P and Demirel, S and Petruzzella, G and Pignataro, M and Boscia, G and Clemente, A and Borrelli, E and Reibaldi, M and Alessio, G and Chhablani, J and Boscia, F},
title = {Choriocapillaris flow in two different patterns of exudative type 1 macular neovascularization.},
journal = {Eye (London, England)},
volume = {39},
number = {3},
pages = {556-562},
pmid = {39794542},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Male ; *Choroid/blood supply ; Female ; Aged ; Fluorescein Angiography/methods ; *Wet Macular Degeneration/physiopathology/diagnosis ; Regional Blood Flow/physiology ; Aged, 80 and over ; Capillaries/physiopathology ; Visual Acuity/physiology ; *Choroidal Neovascularization/physiopathology ; Middle Aged ; Retinal Vessels/physiopathology ; },
abstract = {BACKGROUND: To compare the characteristics of type 1 macular neovascularization (MNV) and the surrounding choriocapillaris (CC) perfusion in patients with neovascular age-related macular degeneration (nAMD) versus those with pachychoroid neovasculopathy (PNV) using swept-source optical coherence tomography angiography (SS-OCTA).<br><br>METHODS: This retrospective study included 64 treatment-na&#xef;ve eyes (37 nAMD, 27 PNV) with type 1 MNV. SS-OCTA images were analysed to measure MNV area and perimeter, and CC flow deficits (FD) in five concentric rings surrounding the lesion. CC FD percentage (FD%), area (FDa), and number (FDn) were quantified. Intervortex anastomoses presence was also assessed.<br><br>RESULTS: MNV lesions in nAMD were significantly larger in area (2.94 vs 1.56&#x2009;mm&#xb2;, p&#x2009;=&#x2009;0.013) and perimeter (8.76 vs 5.85&#x2009;mm, p&#x2009;=&#x2009;0.004) compared to PNV. PNV eyes showed higher FD% and larger FDa across all rings (p&#x2009;<&#x2009;0.05), while FDn did not differ significantly. Intervortex anastomoses were more prevalent in PNV (81.5% vs 35.1%, p&#x2009;=&#x2009;0.0002). In nAMD, MNV size correlated positively with FD% in inner rings and FDn in all rings. In PNV, MNV size correlated only with FDn.<br><br>CONCLUSIONS: Despite smaller MNV lesions, PNV eyes demonstrated more extensive CC flow deficits compared to nAMD. The distinct CC flow patterns and their correlations with MNV characteristics suggest different pathophysiological mechanisms underlying these conditions. These findings may have implications for differential diagnosis and tailored treatment approaches in nAMD and PNV.},
}
@article {pmid39793657,
year = {2025},
author = {Larsen, PP and Delyfer, MN and Schweitzer, C and Korobelnik, JF and Delcourt, C},
title = {Neuroretinal and Retinal Pigment Epithelium Changes and Susceptibility to Age-Related Macular Degeneration: Insights from the Longitudinal ALIENOR Study.},
journal = {Ophthalmology},
volume = {132},
number = {6},
pages = {671-683},
doi = {10.1016/j.ophtha.2025.01.002},
pmid = {39793657},
issn = {1549-4713},
mesh = {Humans ; Female ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Male ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; *Macular Degeneration/diagnosis/epidemiology/genetics ; Aged ; Incidence ; Follow-Up Studies ; Genome-Wide Association Study ; Risk Factors ; Bruch Membrane/pathology ; },
abstract = {PURPOSE: We assessed the associations of macular layer thicknesses, measured using spectral-domain (SD) OCT, with incident age-related macular degeneration (AMD) and AMD polygenic risk scores (PRSs).<br><br>DESIGN: Population-based cohort study.<br><br>PARTICIPANTS: A total of 653 participants from the ALIENOR study, with biennial eye imaging from 2009 through 2024.<br><br>METHODS: Macular layer thicknesses of 8 distinct layers were automatically segmented based on SD-OCT imaging. Total and pathway-specific PRSs were calculated from previous AMD genome-wide association studies summary statistics. Associations of macular layer thicknesses with incident intermediate and advanced AMD were analyzed using time-dependent Cox proportional hazards models. Associations of macular layer thicknesses with PRS were assessed using linear mixed models.<br><br>MAIN OUTCOME MEASURES: Incident intermediate and advanced AMD based on fundus color photographs and SD-OCT.<br><br>RESULTS: Mean age at first OCT examination of the 653 participants was 82.2 &#xb1; 4.2 years, 61.3% of which were women. In multivariable adjusted models, incident intermediate AMD was associated with thicker retinal pigment epithelium (RPE)-Bruch membrane (BM) complex in the 1-mm central circle (hazard ratio [HR], 1.13 for 1-&#x3bc;m increase; P = 8.08 &#xd7; 10[-][4] with false discovery rate [FDR] correction). Incident advanced AMD was associated with thicker RPE-BM complex in both the central (HR, 1.09; PFDR = 0.005) and inner circle (1- to 3 mm; HR, 1.28; PFDR = 1.61 &#xd7; 10[-][5]). Over the study period, RPE-BM complex thickening in the inner circle was more pronounced in individuals with high total PRS (&#x3b2; = 0.06 &#x3bc;m/year for 1-standard deviation increase; PFDR = 1.61 &#xd7; 10[-][10]), high complement pathway PRS (&#x3b2; = 0.04 &#x3bc;m/year; PFDR = 3.23 &#xd7; 10[-][5]), high lipid pathway PRS (&#x3b2; = 0.03 &#x3bc;m/year; PFDR = 3.74 &#xd7; 10[-][4]), and ARMS2 (&#x3b2; = 0.03 &#x3bc;m/year, PFDR = 0.002). High total PRS and high complement-specific PRS were associated with thinner photoreceptor segment layer (PSL) at baseline and longitudinal thinning of the outer nuclear layer.<br><br>CONCLUSIONS: These findings highlight RPE-BM complex thickening in the pathophysiologic sequence of AMD. Further longitudinal studies are needed, in particular to determine the value of RPE-BM thickening and PSL thinning measured using SD-OCT for the clinical follow-up of patients with AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39792775,
year = {2025},
author = {Xu, M and Zhou, Y and Xu, Y and Shao, A and Han, H and Ye, J},
title = {Supramolecular Engineering of Nanoceria for Management and Amelioration of Age-Related Macular Degeneration via the Two-Level Blocking of Oxidative Stress and Inflammation.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {9},
pages = {e2408436},
pmid = {39792775},
issn = {2198-3844},
support = {2024C03204//Key Research and Development Program of Zhejiang Province/ ; 2024C03073//Key Research and Development Program of Zhejiang Province/ ; 82330032//National Natural Science Foundation of China/ ; 82271064//National Natural Science Foundation of China/ ; LR23H120001//Natural Science Foundation of Zhejiang Province/ ; },
mesh = {*Macular Degeneration/drug therapy/metabolism ; *Oxidative Stress/drug effects ; *Cerium/chemistry/pharmacology ; Animals ; Mice ; *Inflammation/drug therapy/metabolism ; Humans ; Choroidal Neovascularization/drug therapy/metabolism ; Reactive Oxygen Species/metabolism ; alpha-Cyclodextrins/chemistry ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {Age-related macular degeneration (AMD), characterized by choroidal neovascularization (CNV), is the global leading cause of irreversible blindness. Current first-line therapeutics, vascular endothelial growth factor (VEGF) antagonists, often yield incomplete and suboptimal vision improvement, necessitating the exploration of novel and efficacious therapeutic approaches. Herein, a supramolecular engineering strategy to construct moringin (MOR) loaded α-cyclodextrin (α-CD) coated nanoceria (M@CCNP) is constructed, where the hydroxy and newly formed carbonyl groups of α-CD interact with the nanoceria surface via O─Ce conjunction and the isothiocyanate group of MOR inserts deeply into the α-CD cavity via host-guest interaction. By exploiting the recycling reactive oxygen species (ROS) scavenging capability of nanoceria and the anti-inflammation properties of MOR, the two-level strike during AMD pathogenesis can be precisely blocked by M@CCNP. Remarkably, excellent therapeutic efficacy to CNV is observed in vivo, achieving over 80% reduction in neovascularization and over 60% reduction in leakage area. In summary, the supramolecular engineered nanoceria provides an efficient approach for amelioration of AMD by blocking the two-level strike, and presents significant potential as an exceptional drug delivery platform, particularly for ROS-related diseases.},
}
@article {pmid39792074,
year = {2025},
author = {Kayembe Mulumba, B and Leffondré, K and Joly, P and Delyfer, MN and Delcourt, C},
title = {Unveiling Statins and Genetics in Age-Related Macular Degeneration Progression: What Is the Appropriate Modeling Strategy?.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {1},
pages = {25},
pmid = {39792074},
issn = {1552-5783},
}
@article {pmid39792057,
year = {2025},
author = {Corti, F and Locri, F and Plastino, F and Perrotta, P and Zsebo, K and Ristori, E and Yin, X and Song, E and André, H and Simons, M},
title = {Anti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {1},
pages = {10},
pmid = {39792057},
issn = {2164-2591},
support = {R01 HL149343/HL/NHLBI NIH HHS/United States ; },
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/pathology ; Mice ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/immunology ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Intravitreal Injections ; Macular Edema/drug therapy/etiology ; Lasers/adverse effects ; Inflammation/drug therapy/pathology ; Capillary Permeability/drug effects ; Humans ; },
abstract = {PURPOSE: Alteration of visual acuity in wet age-related macular degeneration (AMD) is mostly driven by vascular endothelial growth factor A (VEGF-A)-induced edema from leaky newly forming blood vessels below the retina layers. To date, all therapies aimed at alleviation of this process have relied on inhibition of VEGF-A activity. Although effective in preventing vascular leak and edema, this approach also leads to the loss of normal vasculature and multiple related side effects.<br><br>METHODS: We have developed an alternative strategy that uses anti-syndecan-2 polyclonal antibody (anti-Sdc2 pAb) to block VEGF-A-induced permeability without interfering with other VEGF-A activities. The effect of anti-Sdc2 pAb therapy was assessed in vitro using a transendothelial electrical resistance (TEER) assay, as well as staining of the endothelial cell junction, and in vivo in the laser-induced choroidal neovascularization (CNV) model.<br><br>RESULTS: Anti-Sdc2 pAb blocked VEGF-A-induced permeability in vitro, and both local intravitreal injections and systemic intravenous treatments with anti-Sdc2 pAb were as effective as intravitreal anti-VEGF therapy in reducing edema, size of retinal lesions, and local inflammation in this model. Post-injury neovascularization was not affected by treatment with anti-Sdc2 pAb.<br><br>CONCLUSIONS: These findings indicate that anti-Sdc2 pAb therapy can be an effective alternative to anti-VEGF-A approaches for suppression of edema and to prevent retinal lesions in wet neovascular AMD (nAMD).<br><br>TRANSLATIONAL RELEVANCE: Intravitreal anti-Sdc2 treatment may avoid side effects observed with the long-term anti-VEGF therapy, and systemic treatment with an anti-Sdc2 pAb antibody can address the issues associated with repeated intravitreal injections.},
}
@article {pmid39792055,
year = {2025},
author = {Anderson, BD and Bell, BA and Song, Y and Lee, TT and Wang, T and Dunaief, JL},
title = {Systemic Sodium Iodate Injection as a Model for Expanding Geographic Atrophy.},
journal = {Translational vision science &amp; technology},
volume = {14},
number = {1},
pages = {9},
pmid = {39792055},
issn = {2164-2591},
support = {S10 OD026860/OD/NIH HHS/United States ; T32 GM008076/GM/NIGMS NIH HHS/United States ; T32 EY007035/EY/NEI NIH HHS/United States ; R01 EY028916/EY/NEI NIH HHS/United States ; R01 EY015240/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Iodates/administration &amp; dosage ; *Geographic Atrophy/drug therapy ; *Disease Models, Animal ; *Mice, Inbred C57BL ; Male ; *Tomography, Optical Coherence ; Mice ; Injections, Intraperitoneal ; Ophthalmoscopy ; Retinal Pigment Epithelium/pathology/drug effects ; },
abstract = {PURPOSE: Geographic atrophy (GA), an advanced form of dry age-related macular degeneration (AMD), has limited treatment options. This study introduces a novel mouse model featuring an expanding GA patch that can be used to test mechanisms and therapeutics.<br><br>METHODS: C57Bl/6J male mice (n = 96) aged 9-10 weeks received an intraperitoneal (IP) injection of 20&#xa0;mg/kg sodium iodate (NaIO3). In vivo confocal scanning laser ophthalmoscope (cSLO) and optical coherence tomography imaging were done at one, four, eight, and 16 weeks after injection, with GA area measurements taken at weeks 8 and 16. Mice were euthanized on weeks 8 and 16 for histological analysis.<br><br>RESULTS: Administration of 20&#xa0;mg/kg intraperitoneal NaIO3 caused variable damage levels. Approximately 22% of cases showed damage (speckled autofluorescence) covering 35% to 90% of the 102&#xb0; field of view cSLO image at one week after injection. These mice developed an expanding patch of GA by week 8, with a mean 1.45-fold increase in area by week 16. This region showed complete photoreceptor and retinal pigment epithelium loss and complement activation at the atrophy edge, whereas the inner retina remained undamaged. Mice with less damage (48% of cases) only developed incomplete outer retinal degeneration, and mice with more damage (30% of cases) had too much GA for measurable expansion.<br><br>CONCLUSIONS: Although expanding GA formed in only 22% of mice, the model's simplicity and predictability for GA development via one-week post-injection imaging make it suitable for GA therapeutic experimentation.<br><br>TRANSLATIONAL RELEVANCE: This murine model provides a valuable tool for testing GA therapies, mirroring clinical endpoints relevant to human trials.},
}
@article {pmid39791671,
year = {2025},
author = {Archambault, SD and Sweeny, C and Bhardwaj, M and Ramsey, DJ},
title = {Low Vision Rehabilitation Referral Characteristics for Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Healthcare (Basel, Switzerland)},
volume = {13},
number = {1},
pages = {},
pmid = {39791671},
issn = {2227-9032},
abstract = {Background: Despite evidence that low vision rehabilitation (LVR) services can improve visual function in patients with neovascular age-related macular degeneration (nAMD), many patients are not directed to access these resources. This study was conducted to determine factors associated with LVR referral and to assess the visual outcomes from completed evaluations. Methods: The study comprised a retrospective, cross-sectional analysis of patients with nAMD. Referrals for LVR services were extracted from the electronic health record (EHR). The effectiveness of each evaluation was determined by assessing the change in best corrected visual acuity (BCVA) achieved after distance refraction. Costs, quality-adjusted life years (QALYs), and incremental costs per-QALY-gained were calculated based upon the better-seeing eye by using a willingness-to-pay threshold of $50,000/QALY. Results: Out of 560 eligible patients with nAMD, 110 were referred for LVR (19.6%). Referral was more common for individuals who qualified as having low vision, based upon the visual acuity of the better-seeing eye (adjusted odds ratio [aOR], 3.214; 95% confidence interval [CI], 1.920-5.380, p < 0.001), had bilateral nAMD (aOR, 1.592; 95% CI, 1.017-2.492, p = 0.042), or had commercial health insurance compared to those who had Medicare (aOR, 2.887; 95% CI, 1.041-8.009, p = 0.042). Most patients referred completed LVR appointments (86%). More than half of the patients achieved improved BCVA for their better-seeing eye (53%) yielding an average gain of 0.04 QALYs/patient at a cost of $3504/QALY. The estimated net monetary benefit was $1704 per evaluation completed. Conclusions: Most patients with nAMD achieved improvements in visual function after low vision evaluation, yielding improvements in vision-related quality of life at a reasonable cost.},
}
@article {pmid40028045,
year = {2025},
author = {Sedighin, F and Monemian, M and Zojaji, Z and Montazerolghaem, A and Asadinia, MA and Mirghaderi, SM and Esfahani, SAN and Kazemi, M and Mokhtari, R and Mohammadi, M and Ramezani, M and Tajmirriahi, M and Rabbani, H},
title = {Isfahan Artificial Intelligence Event 2023: Macular Pathology Detection Competition.},
journal = {Journal of medical signals and sensors},
volume = {15},
number = {},
pages = {3},
pmid = {40028045},
issn = {2228-7477},
abstract = {BACKGROUND: Computer-aided diagnosis (CAD) methods have become of great interest for diagnosing macular diseases over the past few decades. Artificial intelligence (AI)-based CADs offer several benefits, including speed, objectivity, and thoroughness. They are utilized as an assistance system in various ways, such as highlighting relevant disease indicators to doctors, providing diagnosis suggestions, and presenting similar past cases for comparison.<br><br>METHODS: Much specifically, retinal AI-CADs have been developed to assist ophthalmologists in analyzing optical coherence tomography (OCT) images and making retinal diagnostics simpler and more accurate than before. Retinal AI-CAD technology could provide a new insight for the health care of humans who do not have access to a specialist doctor. AI-based classification methods are critical tools in developing improved retinal AI-CAD technology. The Isfahan AI-2023 challenge has organized a competition to provide objective formal evaluations of alternative tools in this area. In this study, we describe the challenge and those methods that had the most successful algorithms.<br><br>RESULTS: A dataset of OCT images, acquired from normal subjects, patients with diabetic macular edema, and patients with other macular disorders, was provided in a documented format. The dataset, including the labeled training set and unlabeled test set, was made accessible to the participants. The aim of this challenge was to maximize the performance measures for the test labels. Researchers tested their algorithms and competed for the best classification results.<br><br>CONCLUSIONS: The competition is organized to evaluate the current AI-based classification methods in macular pathology detection. We received several submissions to our posted datasets that indicate the growing interest in AI-CAD technology. The results demonstrated that deep learning-based methods can learn essential features of pathologic images, but much care has to be taken in choosing and adapting appropriate models for imbalanced small datasets.},
}
@article {pmid40099606,
year = {2024},
author = {Agarkov, NM and Kopylov, AE and Popova, NV and Shorokhova, AA},
title = {[The effect of sarcopenic obesity and age-associated pathology of the organ of vision on the functional abilities of patients.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {37},
number = {6},
pages = {793-798},
pmid = {40099606},
issn = {1561-9125},
mesh = {Humans ; *Sarcopenia/physiopathology/diagnosis/etiology/epidemiology ; *Obesity/physiopathology/complications/epidemiology ; *Macular Degeneration/physiopathology/diagnosis/epidemiology/complications/etiology ; Male ; Female ; Aged ; *Activities of Daily Living ; Body Mass Index ; Middle Aged ; Aging/physiology ; Vision Disorders/physiopathology/etiology/epidemiology ; },
abstract = {Sarcopenic obesity and visual impairment are considered as two interrelated age-associated conditions that increase the risk of decrease in instrumental activity in everyday life. However, the latter was practically not analyzed in patients with combined sarcopenic obesity and visual impairment due to age-related pathology of the visual organ. The aim of the study was to assess the effect of sarcopenic obesity and age-associated pathology of the visual organ on the functional abilities of patients. 132 patients with sarcopenic obesity and 134 patients with sarcopenic obesity and age-related macular degeneration were examined. The detection of sarcopenic obesity was carried out according to the criteria of reduced muscle strength (or grip strength), reduced muscle mass and increased body mass index (EWGSOP2, 2018). Age-related macular degeneration was diagnosed based on clinical recommendations. Instrumental activity in everyday life was determined by the Lawton scale. It was found that sarcopenic obesity and age-related macular degeneration reduce instrumental activity in daily life to a greater extent (M=4,72±0,07 points) than only sarcopenic obesity (M=5,91±0,09 points), p<0,001. The greatest differences between the groups in the deterioration of instrumental activity in daily life were observed in such types as making phone calls - 0,57±0,05 points among patients with sarcopenic obesity and age-related macular degeneration and 0,89±0,07 points among patients with sarcopenic obesity by 1,56 times (p<0,001), shopping - 0,62±0,06 and 0,76±0,08 points (p<0,01), financial performance - 0,48±0,05 and 0,61±0,04 points (p<0,001), respectively. Therefore, according to these restrictions, patients with sarcopenic obesity and age-related macular degeneration need outside help.},
}
@article {pmid39949759,
year = {2023},
author = {Wu, X and Liszewski, MK and Java, A and Atkinson, JP},
title = {Atypical hemolytic uremic syndrome: genetically-based insights into pathogenesis through an analysis of the complement regulator CD46.},
journal = {Annals of blood},
volume = {8},
number = {},
pages = {},
pmid = {39949759},
issn = {2521-361X},
support = {R01 EY028602/EY/NEI NIH HHS/United States ; R21 AR076534/AR/NIAMS NIH HHS/United States ; R35 GM136352/GM/NIGMS NIH HHS/United States ; },
abstract = {The complement system is a critical innate immune defense mechanism that also facilitates antigen recognition as well as antibody production through the adaptive immune response. Overall, complement activation contributes to the immune system's recognition and response to foreign pathogens and altered self. Regulating complement activation, particularly its powerful alternative pathway (AP) amplification loop, plays a key role in modulating tissue damage at sites of injury. Besides a predisposition to infections and autoimmunity (particularly systemic lupus erythematosus) in individuals deficient in activating components, variants in complement regulators are associated with multiple diseases including atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), and age-related macular degeneration (AMD). In particular, the pathogenesis of aHUS is commonly related to a rare heterozygous loss-of-function (LOF) mutation in the gene for complement factor H (CFH), CD46 [membrane cofactor protein (MCP)] or factor I (CFI) or a gain-of-function (GOF) secondary to a variant in factor B (CFB) or C3. The variants associated with complement regulators are the most prevalent and clearly demonstrate that cofactor activity (CA) is essential to control complement activation and thereby avoid collateral damage to normal tissues. Importantly, multiple studies have now established the therapeutic efficacy of blocking the membrane attack complex (MAC) with a humanized monoclonal antibody that targets the fifth component, C5. In this review, we primarily focus on insights derived from the assessment of rare variants in a membrane complement inhibitor CD46 in aHUS. We also discuss the putative pathological mechanisms relative to these variants of the complement system.},
}
@article {pmid40226407,
year = {2023},
author = {Markey, MW and Pena, CD and Venkatesh, T and Cai, L and Vazquez, M},
title = {Retinal Progenitor Cells Exhibit Cadherin-Dependent Chemotaxis across Transplantable Extracellular Matrix of In Vitro Developmental and Adult Models.},
journal = {Journal of tissue engineering and regenerative medicine},
volume = {2023},
number = {},
pages = {1381620},
pmid = {40226407},
issn = {1932-7005},
support = {R21 EY031439/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Cadherins/metabolism ; *Retina/cytology/metabolism ; *Extracellular Matrix/metabolism ; Drosophila melanogaster ; *Stem Cells/cytology/metabolism ; *Chemotaxis ; *Stem Cell Transplantation ; },
abstract = {Retinal degeneration is an escalating public health challenge, as diseases such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa cause irreversible vision loss in millions of adults each year. Regenerative medicine has pioneered the development of stem cell replacement therapies, which treat degeneration by replacing damaged retinal neurons with transplanted stem-like cells (SCs). While the collective migration of SCs plays critical roles during retinal development, our understanding of collective SC behaviors within biomaterials transplanted into adult tissue remains understudied. This project examines the potential therapeutic impacts of collective SC migration during transplantation by correlating the expression of cadherin, cell-cell cohesion molecules that maintain intercellular communication during development, with receptor proteins of chemoattractant molecules prevalent in degenerated adult tissue. Experiments examine these well-conserved biomechanisms by using two different model organisms: Drosophila melanogaster, a seminal model for retinal development, and Mus, an important preclinical model for transplantation. Results indicate that SCs from both animal models significantly upregulate cadherin expression to achieve more directed collective migration towards species-specific chemoattractants and exhibit longer distance motility upon different extracellular matrix substrates.},
}
@article {pmid40528953,
year = {2025},
author = {Su, W and Gao, Y and Jia, X and Chen, X and Wu, J and Wen, Y and Shi, Y and Zhu, Y and Zhuo, Y},
title = {Single-cell transcriptome atlas of spontaneous dry age-related macular degeneration in macaques.},
journal = {Fundamental research},
volume = {5},
number = {3},
pages = {1034-1046},
pmid = {40528953},
issn = {2667-3258},
abstract = {Age-related macular degeneration is the leading cause of irreversible visual impairment in the elderly. It manifests in two forms, wet and dry. However, the mechanisms underlying spontaneous dry age-related macular degeneration (SD-AMD) remain unclear. Herein, we constructed a single-cell retinal transcription atlas in aged non-human primates with SD-AMD. Retinal tissues affected by SD-AMD exhibited a more degenerative and dysfunctional transcriptomic landscape, with global activation of the oxidative stress response and apoptotic signaling pathway. We found two distinct Müller glia subtypes in normal aged and SD-AMD macaques, one exhibiting a photoreceptor-like transcriptome and the other exhibiting a typical Müller glia transcriptome. As SD-AMD progressed, the proportion of photoreceptor-like Müller glial cells decreased, and photoreceptor-function-associated genes were downregulated, indicating weaker Müller glia potential to transit into photoreceptor-like functional states. Microglial cells showed activated features, and the complement system was activated during disease pathogenesis. We also found that the disruption of iron homeostasis and ferroptosis could promote SD-AMD pathogenesis in neural cells. Further experimentation revealed that a ferroptosis inhibitor exerted a profound rescuing effect in SD-AMD mouse models. Based on these results, our study introduces a path toward understanding the pathogenesis of SD-AMD in a non-human primate model at single-cell resolution.},
}
@article {pmid40103700,
year = {2025},
author = {Luo, Z and Cao, P and Xu, JQ and Yan, R and Wang, J and Liang, T and Chen, Y and Xu, ZC},
title = {A case report: Diagnosis and treatment of idiopathic hypertrophic pachymeningitis.},
journal = {Ibrain},
volume = {11},
number = {1},
pages = {112-116},
pmid = {40103700},
issn = {2769-2795},
abstract = {A 57-year-old man who suffered from a headache for 1 year, accompanied by blurred vision for 7 months and numbness in his left face for 1 week was admitted to the Affiliated Hospital of Zunyi Medical University on May 7, 2022. One year ago, the patient had no obvious precipitating factor of paroxysmal stabbing pain in the whole skull with dizziness, which could be relieved by oneself after lasting for 1-2 min each time, with about 20 episodes per day. The cranial magnetic resonance imaging revealed changes in bilateral frontal lobe ischemic foci, bilateral frontal, ethmoid, sphenoid and maxillary sinusitis, and retinal macular degeneration. After hormone shock treatment, the condition improved. He suffered from headaches again with blurred vision in the right eye 7 months ago and was initially diagnosed with multiple sclerosis. He then was discharged after improvement due to hormone shock therapy. Oral hormone therapy was continued outside the hospital, but he stopped it due to drug side effects (details remained unclear). After cutting off, he developed a headache and visited our hospital once more, the relevant tests were performed and the patient was diagnosed with idiopathic hypertrophic pachymeningitis (IHP). The symptoms were slightly abated after hormone therapy. We hope that through this case report, we can deepen the clinicians' understanding of IHP, and improve the diagnosis rate of the disease through relevant examinations in future clinical work, so that patients can receive timely treatment and the mental pressure and economic burden caused by the disease on patients are reduced.},
}
@article {pmid40115795,
year = {2022},
author = {Suárez Escudero, JC and Oviedo Cáceres, MDP and Llano Naranjo, Y and Arias Uribe, J and Villegas Mesa, JD and Zapata Vásquez, MC and Ferreira Morales, JL and Reyes Cisneros, JT and Cano Calle, K and Goldfeder de Gracia, S and González Franco, JF and Astudillo Valverde, E},
title = {[Etiology of low vision and blindness in seven reference centers in Colombia between the years 2012 to 2017Etiología da baixa visao e cegueira em sete centros de referencia na Colombia entre os anos de 2012 a 2017].},
journal = {Revista Cuidarte},
volume = {13},
number = {2},
pages = {e6},
pmid = {40115795},
issn = {2346-3414},
abstract = {INTRODUCTION: Low vision and blindness have high global prevalence, with categories of disability common in Colombia. Studies that characterize the etiology of permanent visual impairments are required.<br><br>OBJECTIVE: To identify and characterize the different causes of low vision and blindness in seven reference centers for the visually impaired population in Colombia, attended between 2012 and 2017 in six capital cities.<br><br>MATERIALS AND METHODS: retrospective, case series, descriptive and multicenter study.<br><br>RESULTS: A sample of 879 records of visually impaired patients was available. Low vision is more prevalent for all age groups. 70% (612/879) low vision and 30% (267/879) blindness. The most common etiology in patients with low vision was age-related macular degeneration (DMAE) (24%, 144/612); in patients with blindness it was glaucoma (17%, 45/267).<br><br>DISCUSSION: Possibly in Colombia the causes of low vision and blindness go beyond cataracts, un corrected refractive errors and infectious blindness.<br><br>CONCLUSIONS: The most common etiologies found are chronic and diverse eye conditions, which require specific interventions to decrease their prevalence and prevent cases of low vision and blindness.},
}
@article {pmid39791203,
year = {2025},
author = {Jiang, Y and Wen, X and Jian, X and Chen, Q and Li, Y},
title = {Klotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways.},
journal = {International journal of molecular medicine},
volume = {55},
number = {3},
pages = {},
pmid = {39791203},
issn = {1791-244X},
mesh = {*Klotho Proteins ; *Epithelial-Mesenchymal Transition/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; Animals ; *Wnt Signaling Pathway ; *Fibrosis ; Mice ; Humans ; *MAP Kinase Signaling System ; Glucuronidase/metabolism/genetics ; Cell Line ; Male ; Mice, Inbred C57BL ; Cell Proliferation ; Cell Movement ; Transforming Growth Factor beta1/metabolism ; },
abstract = {Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects in multiple fibrotic diseases. However, the mechanisms involved in the role of klotho are unclear in subretinal fibrosis. The aim of the present study was to explore the effects of klotho on subretinal fibrosis induced by laser photocoagulation in mice and EMT induced by TGF‑β1 in RPE cells and the underlying molecular mechanisms. In vitro, klotho overexpression or knockdown was performed in ARPE‑19 cells (adult retinal Pigment Epithelial‑19), then TGF‑β1 treatment was applied. Using western blotting, expression of epithelial markers (zonula occludens‑1), mesenchymal signs (α‑smooth muscle actin, α‑SMA, N‑cadherin, N‑cad and collagen I), and the ERK1/2 and Wnt/β‑catenin signaling pathways were assessed. The proliferative ability of ARPE‑19 cells was examined by CCK‑8 and EdU test, and the migratory ability was examined by wound healing and Transwell assays. Furthermore, to explore the underlying molecular pathway of klotho overexpression, RNA‑sequencing (seq) was performed. In vivo, photocoagulation was used to induce subretinal fibrosis in mice, which occurs as a result of choroidal neovascularization (CNV), then recombinant mouse klotho protein was administered intravitreally. Upregulation of epithelial and downregulation of mesenchymal markers demonstrated that klotho overexpression prevented TGF‑β1‑induced EMT; klotho knockdown resulted in the opposite effects. Additionally, klotho overexpression suppressed cell proliferation and migration and attenuated ERK1/2 and Wnt/β‑catenin signaling activated by TGF‑β1. RNA‑seq results demonstrated that several signaling pathways, including cellular senescence and the TNF signaling pathway, were associated with anti‑fibrotic effects of klotho overexpression. In vivo, subretinal fibrotic areas were attenuated following klotho treatment in laser‑induced CNV lesions, as illustrated by immunofluorescence and Masson staining of the mouse eyes. Western blotting results that the protein levels of mesenchymal markers were significantly downregulated and those of epithelial markers were upregulated. In summary, the present study suggested that klotho may have therapeutic value in management of fibrotic vitreoretinal disorders such as subretinal fibrosis.},
}
@article {pmid39789631,
year = {2025},
author = {Cattaneo, J and Forte, P and Forte, G and Eandi, CM},
title = {Faricimab efficacy in type 1 macular neovascularization: AI-assisted quantification of pigment epithelium detachment (PED) volume reduction over 12 months in Naïve and switch eyes.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {3},
pmid = {39789631},
issn = {2056-9920},
abstract = {BACKGROUND: This study evaluates the efficacy of intravitreal Faricimab in reducing pigment epithelium detachment (PED) and fluid volumes in both treatment-naïve eyes and eyes unresponsive to anti-VEGF mono-therapies, all diagnosed with type 1 macular neovascularization (T1 MNV) over a period of 12-month.<br><br>METHODS: A retrospective, single-center cohort study was conducted at the Jules Gonin Eye Hospital, Lausanne, Switzerland. Clinical records of treatment-na&#xef;ve and non-responder switch patients presenting T1 MNV secondary to neovascular age-related macular degeneration (nAMD) from September 2022 to March 2023 were reviewed. Patients received a loading dose of three monthly Faricimab injections followed by a treat-and-extend (T&amp;E) regimen. Multimodal imaging, including structural OCT and AI-assisted analysis, was used to quantify PED volumes and related fluid biomarkers at baseline, 3-month, 6-month, and 12-month follow-up. Statistical analyses included linear mixed models to evaluate differences and trends in intraretinal (IRF), subretinal fluid (SRF) and PED volumes.<br><br>RESULTS: 65 eyes of 65 patients were enrolled (female: 70.7%; mean age&#x2009;=&#x2009;80.7yrs, SD&#x2009;=&#x2009;6.9yrs). 80% had received anti-VEGF treatment (Switch group) and 20% were treatment-Na&#xef;ve at baseline. At 12 months, intravitreal treatments were more frequent in the Switch group (mean number&#x2009;=&#x2009;8.3 vs. 6.0; p&#x2009;=&#x2009;0.009). BCVA improved at the 12-month follow-up in Na&#xef;ve eyes (+&#x2009;6.9 ETDRS letters from baseline, p&#x2009;=&#x2009;0.053) and was maintained in Switch eyes. No cases of intraocular inflammation were observed. Significant reduction in SRF and IRF volumes were noted in both groups. A significant reduction in PED volume was observed over the follow-up period in both groups (mean slope = -206 nL, 95%CL = -273/-138; p-value&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Intravitreal Faricimab significantly reduced PED volumes in both treatment-Na&#xef;ve and non-responder Switch patients over 12 months. The study highlights Faricimab's potential as an effective treatment option for T1 MNV in nAMD, offering significant improvements in PED volume and related fluid biomarkers.},
}
@article {pmid39787576,
year = {2025},
author = {},
title = {Drugs for age-related macular degeneration.},
journal = {The Medical letter on drugs and therapeutics},
volume = {67},
number = {1719},
pages = {1-5},
doi = {10.58347/tml.2025.1719a},
pmid = {39787576},
issn = {1523-2859},
}
@article {pmid39787548,
year = {2024},
author = {Wang, Y and Wang, L and Lin, S and Zhang, Z and Li, X and Lin, L},
title = {Relationship between Age-Related Hearing Loss and Age-Related Macular Degeneration.},
journal = {Noise &amp; health},
volume = {26},
number = {123},
pages = {483-488},
pmid = {39787548},
issn = {1998-4030},
mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; Male ; Aged ; Female ; Middle Aged ; Risk Factors ; *Presbycusis/epidemiology/etiology ; Aged, 80 and over ; Age Factors ; China/epidemiology ; Noise/adverse effects ; Cohort Studies ; },
abstract = {BACKGROUND: With the aging of the population, the deterioration of visual and auditory functions amongst the elderly has attracted much attention. Age-related hearing loss (ARHL) and age-related macular degeneration (AMD) are common eye and ear diseases that seriously affect the quality of life of elderly population.<br><br>METHODS: This study utilised a whole cohort sampling method, with a total of 713 participants aged 50 years and older in the community from June 2022 to October 2023, resulting in the inclusion of 620 participants. Demographic information was collected from these participants, and eye and hearing examinations were conducted at Ningde Municipal Hospital affiliated of Fujian Medical University. Spearman's correlation analysis was utilised to investigate the association between ARHL and AMD in patients. Multivariate logistic regression analysis was employed to identify the factors influencing ARHL to provide insights for preventing and treating ARHL and AMD in older individuals.<br><br>RESULTS: Correlation analysis indicated a significantly positive relationship between ARHL and AMD (P < 0.001). The results showed that age, medical history, AMD and chronic noise exposure were risk factors for ARHL.<br><br>CONCLUSIONS: There were 196 cases of AMD in ARHL patients (82.35%). Spearman's correlation analysis revealed that ARHL was associated with AMD; logistic regression analysis revealed that age, medical history, macular degeneration and history of prolonged noise exposure were risk factors for ARHL. Among them, age, medical history (hypertension, hyperlipidaemia and diabetes mellitus), noise and AMD influence the development of ARHL in the elderly population. Therefore, attention should be paid to controlling risk factors in this population to prevent or reduce the development of ARHL.},
}
@article {pmid39779923,
year = {2025},
author = {Muller, A and Sullivan, J and Schwarzer, W and Wang, M and Park-Windhol, C and Hasler, PW and Janeschitz-Kriegl, L and Duman, M and Klingler, B and Matsell, J and Hostettler, SM and Galliker, P and Hou, Y and Balmer, P and Virág, T and Barrera, LA and Young, L and Xu, Q and Magda, DP and Kilin, F and Khadka, A and Moreau, PH and Fellmann, L and Azoulay, T and Quinodoz, M and Karademir, D and Leppert, J and Fratzl, A and Kosche, G and Sharma, R and Montford, J and Cattaneo, M and Croyal, M and Cronin, T and Picelli, S and Grison, A and Cowan, CS and Kusnyerik, &#xc1; and Anders, P and Renner, M and Nagy, ZZ and Szabó, A and Bharti, K and Rivolta, C and Scholl, HPN and Bryson, D and Ciaramella, G and Roska, B and György, B},
title = {High-efficiency base editing in the retina in primates and human tissues.},
journal = {Nature medicine},
volume = {31},
number = {2},
pages = {490-501},
pmid = {39779923},
issn = {1546-170X},
support = {ProgStar Study//Foundation Fighting Blindness (FFB)/ ; #204285//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; #PCEFP3_202756//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; #310030_192665//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; postdoctoral fellowship ALTF 688-2022//European Molecular Biology Organization (EMBO)/ ; /WT_/Wellcome Trust/United Kingdom ; PINNACLE Study//Wellcome Trust (Wellcome)/ ; },
mesh = {Humans ; *Gene Editing/methods ; Animals ; *Retina/metabolism ; Mice ; Retinal Pigment Epithelium/metabolism ; Female ; Genetic Therapy/methods ; Induced Pluripotent Stem Cells/metabolism ; Stargardt Disease/genetics/therapy ; Dependovirus/genetics ; Organoids/metabolism ; Mutation ; Primates ; Genetic Vectors/genetics ; Male ; ATP-Binding Cassette Transporters ; },
abstract = {Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.Gly1961Glu). We optimized ABCA4 base editing in human models, including retinal organoids, induced pluripotent stem cell-derived retinal pigment epithelial (RPE) cells, as well as adult human retinal explants and RPE/choroid explants in vitro. The resulting gene therapy vectors achieved high levels of gene correction in mutation-carrying mice and in female nonhuman primates, with average editing of 75% of cones and 87% of RPE cells in vivo, which has the potential to translate to a clinical benefit. No off-target editing was detectable in human retinal explants and RPE/choroid explants. The high editing rates in primates show promise for efficient gene editing in other ocular diseases that are targetable by base editing.},
}
@article {pmid39779776,
year = {2025},
author = {Idrees, N and Noor, E and Rashid, S and Agama, FT},
title = {Role of topological indices in predictive modeling and ranking of drugs treating eye disorders.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {1271},
pmid = {39779776},
issn = {2045-2322},
mesh = {*Eye Diseases/drug therapy ; Humans ; *Quantitative Structure-Activity Relationship ; Machine Learning ; Drug Design ; },
abstract = {Topological indices (TIs) of chemical graphs of drugs hold the potential to compute important properties and biological activities leading to more thoughtful drug design. Here, we considered certain drugs treating eye-related disorders, including cataract, glaucoma, diabetic retinopathy, and macular degeneration. By combining modeling and decision-makings approaches, this study presents a cost-effective way to comprehend the behavior of molecules. First, the topological indices of chemical graphs of molecules are determined, which provides valuable insights into their behavior. These models are first trained using known data and are also validated by the dataset of known properties. Models for quantitative structure property relations (QSPR) are computed using the quadratic regression method. TIs having correlation value greater than 0.7 with properties like molar weight, index of refraction, molar volume, polarizability, and molar refraction are taken in this work. Weights are assigned to different properties of drugs depending upon the correlation of the properties with topological indices. Furthermore, we used the multiple-choice decision-making techniques TOPSIS and SAW, to rank the drugs treating eye disorders to create well-informed selections. We can precisely forecast the behavior of chemicals by utilizing machine learning to analyze large amounts of data. This method may contribute to the discovery of new relevant drugs with desirable properties and helpful in comprehending the effects of chemicals on their efficacy.},
}
@article {pmid39779283,
year = {2025},
author = {Foo, LL and Jiang, Y and Hoang, QV and Htoon, HM and Hu, Z and Pan, W and Cheong, KX and Lamoureux, EL and Yang, Z and Lan, W and Saw, SM},
title = {Prevalence and risk factors of myopic macular degeneration: the Aier-SERI high myopia adult cohort.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {6},
pages = {721-726},
doi = {10.1136/bjo-2024-326116},
pmid = {39779283},
issn = {1468-2079},
mesh = {Humans ; Male ; Prevalence ; Female ; Risk Factors ; Adult ; Middle Aged ; China/epidemiology ; *Myopia, Degenerative/epidemiology/diagnosis/physiopathology/complications ; *Refraction, Ocular/physiology ; *Macular Degeneration/epidemiology/etiology/diagnosis ; Visual Acuity/physiology ; Biometry ; Axial Length, Eye/pathology ; },
abstract = {PURPOSE: To assess the prevalence and risk factors of myopic macular degeneration (MMD) in young and middle-aged individuals with high myopia in Changsha, central China.<br><br>METHODS: A total of 445 adults with high myopia (worse than or equal to -5.0 D) were examined between 2021 and 2023. Autorefraction and biometry using IOLMaster were conducted, and fundus photos were graded for MMD using Meta-PM criteria. MMD was diagnosed if category 2, 3, 4 or any plus lesion was present. Risk factors such as age, gender, spherical equivalent (SE)/axial length (AL), body mass index, education and residence were analysed via logistic regression.<br><br>RESULTS: Participants had an average age of 42.3&#xb1;7.3 years. MMD prevalence was 21.8% (71 adults) with a mean SE of -9.5&#xb1;4.7 D and AL of 27.3&#xb1;1.9&#x2009;mm. Significant risk factors included greater myopic SE (OR=1.7 per 1 D decrease) and longer AL (OR=3.6 per 1&#x2009;mm increase). MMD prevalence rose sharply with myopia worse than -10.00 D and AL >27.00&#x2009;mm, reaching up to 100% for myopia worse than -14.00 D or AL &#x2265;29.00&#x2009;mm.<br><br>CONCLUSION: MMD affects about one in five young to middle-aged adults with high myopia. Those exceeding critical myopia and AL thresholds are at higher risk and should be closely monitored. Further research on interventions to prevent axial elongation is needed, particularly for those with high genetic risk.},
}
@article {pmid39778903,
year = {2025},
author = {Sadikan, MZ and Lambuk, L and Reshidan, N and Ahmad Hairi, H and Abd Ghapor, AA and Mohamud, R and Abdul Nasir, NA},
title = {Molecular Mechanisms of Vitamin E in Ocular Neurodegenerative Disorders: An Update on the Emerging Evidence and Therapeutic Implications.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {41},
number = {3},
pages = {89-100},
doi = {10.1089/jop.2024.0125},
pmid = {39778903},
issn = {1557-7732},
mesh = {Humans ; *Vitamin E/pharmacology/therapeutic use/administration &amp; dosage ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Antioxidants/pharmacology/therapeutic use/administration &amp; dosage ; Animals ; Oxidative Stress/drug effects ; *Eye Diseases/drug therapy ; Macular Degeneration/drug therapy ; Vitamin E Deficiency/drug therapy ; Anti-Inflammatory Agents/pharmacology ; },
abstract = {Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due to its pivotal role in preserving cell membrane integrity and combating cellular oxidative damage. While its importance for overall health, including neurodegeneration, is acknowledged, the specific correlation between vitamin E deficiency and distinct ocular neurodegenerative disorders need to be further explored. This review delves into the molecular mechanisms of vitamin E in ocular neurodegenerative disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts, and emphasising the therapeutic implications drawn from existing evidence. Relationship between vitamin E and ocular neurodegenerative disorders is widely researched on, with its primary protective mechanisms attributed to its antioxidant and anti-inflammatory properties. However, studies on the supplementation of vitamin E among human subjects present mixed results, suggesting its complexities and variability depending on factors such as the specific disorder, disease stage, genetic differences, and form of vitamin E utilized. In conclusion, while vitamin E holds promise in mitigating ocular neurodegeneration through its antioxidant and anti-inflammatory properties, its supplementation's efficacy remains nuanced and context dependent. More research works are essential to elucidate its precise role and therapeutic potential in combating various ocular neurodegenerative disorders.},
}
@article {pmid39778673,
year = {2025},
author = {Wang, Y and Ma, H and Yang, Q and Chen, K and Ye, H and Wang, X and Xia, J and Chen, X and Wang, X and Shen, Y and Cui, H},
title = {Senescent retinal pigment epithelial cells promote angiogenesis in choroidal neovascularization via the TAK1/p38 MAPK pathway.},
journal = {Experimental eye research},
volume = {251},
number = {},
pages = {110232},
doi = {10.1016/j.exer.2025.110232},
pmid = {39778673},
issn = {1096-0007},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology ; *Retinal Pigment Epithelium/pathology/metabolism ; *MAP Kinase Kinase Kinases/metabolism ; Rats ; Humans ; Rats, Inbred BN ; *p38 Mitogen-Activated Protein Kinases/metabolism ; Cell Movement/physiology ; Disease Models, Animal ; *Cellular Senescence/physiology ; Human Umbilical Vein Endothelial Cells ; Wound Healing/physiology ; Cell Survival ; Male ; Cells, Cultured ; *MAP Kinase Signaling System/physiology ; Blotting, Western ; Angiogenesis ; },
abstract = {Senescent retinal pigment epithelial cells play a key role in neovascular age-related macular degeneration (nAMD); however, the mechanisms underlying the angiogenic ability of these cells remain unclear. Herein, we investigated the effects of the senescent adult retinal pigment epithelial cell line-19 (ARPE-19) on wound healing, cell migration and survival, and tube formation abilities of human umbilical vein endothelial cells (HUVECs). Additionally, we used Brown Norway rats to establish a laser-induced choroidal neovascularization (CNV) model for further nAMD-related studies. We found that the wound healing, cell migration, and tube formation abilities of HUVECs were significantly enhanced following culture in conditioned media from senescent ARPE-19 cells; this was attributed to the activation of the transforming growth factor β-activated kinase 1 (TAK1)/p38 MAPK pathway. Consistently, we found that the TAK1 inhibitors 5Z-7-oxozeaenol and takinib reversed the effects of conditioned media from senescent ARPE-19 cells on the wound healing, migration, survival, and tube formation abilities of HUVECs. We further investigated the therapeutic effects of 5Z-7-oxozeaenol on the laser-induced CNV rat model. We found that TAK1 was activated in IB4+ areas in laser-induced CNV lesions; inhibiting the activity of TAK1 using 5Z-7-oxozeaenol significantly alleviated CNV lesion formation and fluorescein leakage in fundus fluorescein angiography and greatly improved a-waves, b-waves, and OP values, as recorded by electroretinography. Thus, senescent RPE cells may promote angiogenesis via the TAK1/p38 MAPK pathway. Further, inhibiting TAK1 expression alleviates pathological neovascularization and improves retinal function in a laser-induced CNV rat model, highlighting the therapeutic potential of this approach for treating nAMD.},
}
@article {pmid39778117,
year = {2025},
author = {Shelton, A and Schutten, M and Fuji, RN and Boyd, R and Stevenson, V and Leahy, M and Knupp, L and Lieng, J and Thompson, D and Tam, T and LaMarche, K and Barteselli, G and Malhotra, V and Bantseev, V},
title = {TRANSSCLERAL PARS PLANA CHOROID ABLATION USING THE IRIDEX LASER SYSTEM YIELDS IMPROVEMENTS FOR SURGICAL INSERTION OF THE PORT DELIVERY IMPLANT IN A MINIPIG MODEL.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {5},
pages = {996-1005},
doi = {10.1097/IAE.0000000000004385},
pmid = {39778117},
issn = {1539-2864},
mesh = {Animals ; Swine ; Swine, Miniature ; Male ; *Sclera/surgery ; Disease Models, Animal ; *Choroid/surgery ; *Lasers, Semiconductor/therapeutic use ; Drug Implants ; *Laser Therapy/methods ; Angiogenesis Inhibitors/administration &amp; dosage ; },
abstract = {PURPOSE: To evaluate an alternative surgical approach for Port Delivery System with ranibizumab implant and a novel application of Iridex laser system in Gottingen minipig model.<br><br>METHODS: A total of 17 male minipigs (Part 1: nine animals in nonrecovery and Part 2: eight animals observed for 8 days after surgery Part 2) received Port Delivery System implant insertion into each eye. The effect of Iridex 810-nm infrared diode laser with varying energy (power or duration) on transscleral pars plana ablation surrounding ocular tissue and postsurgical vitreous hemorrhage was investigated.<br><br>RESULTS: The most effective laser parameters for transscleral pars plana ablation in mitigating vitreous hemorrhage with no surrounding tissue damage were continuous wave mode, 1,750 mW, 1,000 ms, and 16 spots (eight overlapping spots/sweep applied over two rows) across a 4 mm segment, posterior to the limbus, delivering a total energy of 28 J. Minimal self-limiting scleral hemorrhage was observed with two of the implants, and no vitreous hemorrhage was observed. Microcomputed tomography imaging was consistent with clinical ophthalmic observations. On microscopic observations, no tissue damage was observed at these laser settings.<br><br>CONCLUSION: This G&#xf6;ttingen minipig model demonstrated a novel application of Iridex laser for transscleral pars plana ablation that streamlines the Port Delivery System implantation surgery.},
}
@article {pmid39777090,
year = {2024},
author = {Limoli, PG and Limoli, C and Nebbioso, M},
title = {Potential guidelines for cataract surgery and rehabilitation in visually impaired patients: Literature analysis.},
journal = {Aging medicine (Milton (N.S.W))},
volume = {7},
number = {6},
pages = {802-812},
pmid = {39777090},
issn = {2475-0360},
abstract = {Cataracts can reduce the quality of vision in visually impaired patients who already have a visual impairment. The most common causes of low vision include age-related macular degeneration (AMD), high myopia (HM), diabetic retinopathy (DR), glaucoma (GL), and inherited degenerative ocular diseases. The surgery aims to improve their independence, quality of life, and ability to engage in daily, social, and work activities. Phacoemulsification and intraocular lens (IOL) implantation, combined with visual rehabilitation, can improve visual acuity of visually impaired patients. Therefore, comprehensive guidelines for cataract surgery in patients with low vision would be beneficial to ensure optimal surgical outcomes by improving surgical planning, execution, and postoperative care, along with a well-coordinated rehabilitation process. In cases of reduced metabolism, such as low vision, oxidative stress can be aggravated by light exposure and surgical interventions. Thus, maintaining redox balance is crucial for stabilizing retinal conditions. Patients with visual impairments rely on retinal regions with the greatest residual function, and cataract surgery aims to enhance focus on these areas, improving reading quality and reducing scotoma perception. Thorough informed consent is crucial, ensuring that patients are fully aware of the potential risks, benefits, and limitations of surgery. Close postoperative follow-up in the first 6 months is crucial to detect and manage any complications promptly, such as reactivation of maculopathy. The aim of this work is to establish potential guidelines for optimal rehabilitation outcomes through careful literature analysis.},
}
@article {pmid39776840,
year = {2024},
author = {Wei, X and Yang, H and Yin, X and Fu, Z and Xiong, W},
title = {Exploring causal relationships between immune cells and age-related macular degeneration through univariable, bidirectional, and multivariable Mendelian analysis.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1444277},
pmid = {39776840},
issn = {2296-858X},
abstract = {OBJECTIVE: This study systematically investigates the causal relationships between 731 immune cell phenotypes and age-related macular degeneration (AMD) using comprehensive Mendelian randomization (MR) analyses. The goal is to identify immune cell factors that contribute to or protect against AMD, thereby clarifying the immunological mechanisms underlying AMD pathophysiology and informing prevention and treatment strategies.<br><br>METHODS: Univariable, bidirectional, and multivariable MR analyses were conducted to evaluate the associations between immune cells and AMD. By utilizing publicly available GWAS datasets, we eliminated the need for individual consents. The large-scale MR approach adhered to STROBE-MR guidelines. Immune cell GWAS data were sourced from a study involving 3,757 Sardinians, encompassing a broad spectrum of immune phenotypes, while AMD summary statistics were derived from a GWAS with over 3,763 cases. Instrumental variables (IVs) were carefully selected to comply with MR assumptions, and multiple MR methods were employed to enhance the robustness of causal inferences. Additionally, we supplemented the data for dry AMD (2,469 cases and 206,221 controls) and wet AMD (2,114 cases and 206,601 controls) for validation purposes.<br><br>RESULTS: Univariable MR analysis identified 17 immune cell phenotypes significantly associated with AMD, including 11 potential risk factors and 6 potential protective factors. Bidirectional MR analysis found no significant effects of AMD on the examined immune cell subsets. Multivariable MR analysis indicated that TD CD4+ %T cells and CD39+ CD8br %T cells likely inhibit AMD development, whereas CD39+ CD8br %CD8br cells and CD45RA on resting Treg cells appear to increase AMD risk. Validation of immune cell subsets in dry and wet AMD revealed significant associations between specific immune cells and both forms of AMD, with some subsets uniquely linked to wet AMD and others to dry AMD.<br><br>CONCLUSION: This study addresses a critical gap in understanding the causal relationship between immune cells and AMD, identifying immune cell subsets that may either mitigate or exacerbate AMD risk. Notably, it highlights the potential role of CD39+ CD8+ T cells as anti-inflammatory agents and potential targets for immunotherapy in AMD. The absence of bidirectional causality suggests a complex origin of immune dysregulation in AMD. The differential associations of immune cell subsets with AMD subtypes carry significant implications for precision medicine approaches in ophthalmology, laying a solid foundation for future research focused on understanding the immunological underpinnings of AMD and developing targeted therapeutic strategies.},
}
@article {pmid39775695,
year = {2025},
author = {Behnke, V and Wolf, A and Hector, M and Langmann, T},
title = {C3aR1-Deletion Delays Retinal Degeneration in a White-Light Damage Mouse Model.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {1},
pages = {15},
pmid = {39775695},
issn = {1552-5783},
mesh = {Animals ; Mice ; *Mice, Knockout ; *Disease Models, Animal ; *Retinal Degeneration/metabolism/etiology/genetics/pathology ; *Light/adverse effects ; *Mice, Inbred C57BL ; Microglia/metabolism/pathology ; Retina/metabolism/pathology/radiation effects ; Receptor, Anaphylatoxin C5a/genetics/metabolism ; Receptors, Complement/genetics/metabolism ; Radiation Injuries, Experimental/pathology/metabolism/genetics ; Calcium-Binding Proteins ; Microfilament Proteins ; Receptors, G-Protein-Coupled ; },
abstract = {PURPOSE: In the aging retina, persistent activation of microglia is known to play a key role in retinal degenerative diseases like age-related macular degeneration (AMD). Furthermore, dysregulation of the alternative complement pathway is generally accepted as the main driver for AMD disease progression and microglia are important producers of local complement and are equipped with complement receptors themselves. Here, we investigate the involvement of anaphylatoxin signaling, predominantly on Iba1+ cell activity, in light-induced retinal degeneration as a model for dry AMD, using anaphylatoxin receptor knockout (KO) mice.<br><br>METHODS: Bright white light with an intensity of 10,000 lux was applied for 30 minutes to complement component 3a receptor 1 (C3ar1) or complement component 5a receptor 1 (C5ar1) KO and wildtype (WT) mice. Analyses of transcriptome changes and migration activity of Iba1+ cells as well as retinal thickness were performed 4 days after light exposure.<br><br>RESULTS: Full body KO mice of either C3aR1 or C5aR1 were tested, but none led to mitigated migration of Iba1+ cells to the subretinal space or decreased expression of complement factors after light damage compared to WT mice. However, a partial rescue of retinal thickness was shown in C3aR1 KO mice, which was mirrored by significant less membrane attack complex (MAC) occurrence in the outer retina.<br><br>CONCLUSIONS: We conclude that deletion of the anaphylatoxin receptor C3aR1 cannot modulate mononuclear phagocytes but diminishes retinal degeneration through interference with the complement pathway and thus decreased MAC assembling. C3aR1-targeted therapy may be considered for patients with dry AMD.},
}
@article {pmid39774257,
year = {2025},
author = {Chen, X and Wu, S and Wang, S and Yu, C and Guo, Z and Huang, S and Cai, P and Miao, Y and Li, S and Chen, Q},
title = {Real world pharmacovigilance assessment of drug related macular degeneration risks.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {1220},
pmid = {39774257},
issn = {2045-2322},
support = {20720220056//Fundamental Research Funds for Xiamen University/ ; 3502Z202372007//Natural Science Youth Foundation of Xiamen City/ ; 2023J011585//Natural Science Foundation of Fujian Province/ ; },
mesh = {Humans ; *Macular Degeneration/chemically induced/drug therapy/epidemiology ; *Pharmacovigilance ; Female ; Male ; *Adverse Drug Reaction Reporting Systems/statistics &amp; numerical data ; Aged ; Middle Aged ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; United States/epidemiology ; Aged, 80 and over ; },
abstract = {Macular degeneration is a leading cause of irreversible vision loss, significantly impacting quality of life. To enhance clinical practice and reduce the risk of drug-related macular degeneration, we analyzed drug-related trends using real-world data. Disproportionality analysis of adverse event reports from the FDA Adverse Event Reporting System (FAERS, 2004-2023) identified 67,683 cases involving 1402 drugs. Among these, 42 drugs were linked to significant risks, including treatments for breast cancer (tamoxifen, raloxifene, anastrozole, letrozole) and diabetes (insulin lispro, insulin human). The BCPNN algorithm revealed that 45.2% (19/42) of these drugs had the strongest associations with macular degeneration, with pentosan polysulfate sodium, travoprost, and tolterodine being the highest-risk drugs. Lifitegrast, nicotine, and travoprost were associated with the shortest onset times for ocular adverse events. Among drug classes, glucocorticosteroids were linked to the most rapid onset of ocular side effects (P < 0.001), typically occurring within two months compared to other drugs. Drug-related macular degeneration was more common in women (70.4%) and predominantly affected those aged 60-80. The incidence of drug-related macular degeneration has steadily increased in recent years. This study offers valuable pharmacovigilance insights, highlighting drugs and demographic factors linked to macular degeneration.},
}
@article {pmid39774017,
year = {2025},
author = {Yap, WS and Cengnata, A and Saw, WY and Abdul Rahman, T and Teo, YY and Lim, RL and Hoh, BP},
title = {High-coverage whole-genome sequencing of a Jakun individual from the "Orang Asli" Proto-Malay subtribe from Peninsular Malaysia.},
journal = {Human genome variation},
volume = {12},
number = {1},
pages = {4},
pmid = {39774017},
issn = {2054-345X},
abstract = {Jakun, a Proto-Malay subtribe from Peninsular Malaysia, is believed to have inhabited the Malay Archipelago during the period of agricultural expansion approximately 4 thousand years ago (kya). However, their genetic structure and population history remain inconclusive. In this study, we report the genome structure of a Jakun female, based on whole-genome sequencing, which yielded an average coverage of 35.97-fold. We identified approximately 3.6 million single-nucleotide variations (SNVs) and 517,784 small insertions/deletions (indels). Of these, 39,916 SNVs were novel (referencing dbSNP151), and 10,167 were nonsynonymous (nsSNVs), spanning 5674 genes. Principal Component Analysis (PCA) revealed that the Jakun genome sequence closely clustered with the genomes of the Cambodians (CAM) and the Metropolitan Malays from Singapore (SG_MAS). The ADMIXTURE analysis further revealed potential admixture from the EA and North Borneo populations, as corroborated by the results from the F3, F4, and TreeMix analyses. Mitochondrial DNA analysis revealed that the Jakun genome carried the N21a haplogroup (estimated to have occurred ~19 kya), which is commonly found among Malays from Malaysia and Indonesia. From the whole-genome sequence data, we identified 825 damaging and deleterious nonsynonymous single-nucleotide polymorphisms (nsSNVs) affecting 720 genes. Some of these variants are associated with age-related macular degeneration, atrial fibrillation, and HDL cholesterol level. Additionally, we located a total of 3310 variants on 32 core adsorption, distribution, metabolism, and elimination (ADME) genes. Of these, 193 variants are listed in PharmGKB, and 21 are nsSNVs. In summary, the genetic structure identified in the Jakun individual could enhance the mapping of genetic variants for disease-based population studies and further our understanding of the human migration history in Southeast Asia.},
}
@article {pmid39773983,
year = {2025},
author = {R, L and S, L},
title = {Enhanced AMD detection in OCT images using GLCM texture features with Machine Learning and CNN methods.},
journal = {Biomedical physics &amp; engineering express},
volume = {11},
number = {2},
pages = {},
doi = {10.1088/2057-1976/ada6bc},
pmid = {39773983},
issn = {2057-1976},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging ; *Machine Learning ; *Neural Networks, Computer ; *Image Processing, Computer-Assisted/methods ; Algorithms ; Retina/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; },
abstract = {Global blindness is substantially influenced by age-related macular degeneration (AMD). It significantly shortens people's lives and severely impairs their visual acuity. AMD is becoming more common, requiring improved diagnostic and prognostic methods. Treatment efficacy and patient survival rates stand to benefit greatly from these upgrades. To improve AMD diagnosis in preprocessed retinal images, this study uses Grey Level Co-occurrence Matrix (GLCM) features for texture analysis. The selected GLCM features include contrast and dissimilarity. Notably, grayscale pixel values were also integrated into the analysis. Key factors such as contrast, correlation, energy, and homogeneity were identified as the primary focuses of the study. Various supervised machine learning (ML) and CNN techniques were employed on Optical Coherence Tomography (OCT) image datasets. The impact of feature selection on model performance is evaluated by comparing all GLCM features, selected GLCM features, and grayscale pixel features. Models using GSF features showed low accuracy, with OCTID at 23% and Kermany at 54% for BC, and 23% and 53% for CNN. In contrast, GLCM features achieved 98% for OCTID and 73% for Kermany in RF, and 83% and 77% in CNN. SFGLCM features performed the best, achieving 98% for OCTID across both RF and CNN, and 77% for Kermany. Overall, SFGLCM and GLCM features outperformed GSF, improving accuracy, generalization, and reducing overfitting for AMD detection. The Python-based research demonstrates ML's potential in ophthalmology to enhance patient outcomes.},
}
@article {pmid39773551,
year = {2025},
author = {Alibhai, AY and Moult, EM and Jamil, MU and Raza, K and Morales, MU and Ribeiro, R and Baumal, CR and Fujimoto, JG and Waheed, NK},
title = {Evaluating the reliability of a microperimetry-based method for assessing visual function in the junctional zone of geographic atrophy lesions.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {1},
pmid = {39773551},
issn = {2056-9920},
support = {R01 EY011289/EY/NEI NIH HHS/United States ; R01EY011289/NH/NIH HHS/United States ; },
abstract = {PURPOSE: To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.<br><br>METHODS: A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10&#x2009;-&#x2009;2 fovea centered grid was performed at baseline and follow-up visits. GA regions were traced on fundus autofluorescence (FAF) images. Two graders independently registered baseline microperimetry images with baseline FAF images in a sampling of 30 eyes from the OAKS study. Agreement between the two graders' assessments of mean sensitivity and the number of scotomatous points within a&#x2009;&#xb1;&#x2009;250 &#x1d707;m GA junctional zone was assessed.<br><br>RESULTS: The intraclass correlation (ICC) and coefficient of repeatability (CoR) for the mean junctional zone sensitivity were 0.987 and 0.214 dB, respectively. The ICC and CoR for the total number of scotomatous points within the junctional zone were 0.991 and 1.42, respectively.<br><br>CONCLUSIONS: The repeatability of the methodology and its compatibility with standard MP acquisitions appear to make it well-suited for identifying and analyzing retinal sensitivity within high-risk areas of the retina. We present a microperimetry-based methodology for assessing visual function changes in the junctional zone of geographic atrophy lesions using a standard 10&#x2009;-&#x2009;2 fovea centered grid in a clinical trial context. The approach's repeatability and compatibility with standard microperimetry grids may make it useful for assessing the effects of GA therapeutics.},
}
@article {pmid39769385,
year = {2024},
author = {Yang, B and Yang, K and Xi, R and Chen, J and Wu, Y},
title = {Quercetin Alleviates All-Trans-Retinal-Induced Photoreceptor Apoptosis and Retinal Degeneration by Inhibiting the ER Stress-Related PERK Signaling.},
journal = {International journal of molecular sciences},
volume = {25},
number = {24},
pages = {},
pmid = {39769385},
issn = {1422-0067},
support = {82171064//National Natural Science Foundation of China/ ; 82471093//National Natural Science Foundation of China/ ; 2022A1515012514//Guangdong Basic and Applied Basic Research Foundation/ ; JCYJ20230807091503007//Shenzhen Science and Technology Program/ ; },
mesh = {*Quercetin/pharmacology ; Animals ; *Endoplasmic Reticulum Stress/drug effects ; *eIF-2 Kinase/metabolism/genetics ; *Apoptosis/drug effects ; *Retinal Degeneration/drug therapy/metabolism/pathology ; Mice ; *Signal Transduction/drug effects ; *Reactive Oxygen Species/metabolism ; *Retinaldehyde/metabolism ; Photoreceptor Cells, Vertebrate/drug effects/metabolism/pathology ; Antioxidants/pharmacology ; Mice, Knockout ; Cell Survival/drug effects ; Disease Models, Animal ; Cell Line ; Photoreceptor Cells/drug effects/metabolism ; Alcohol Oxidoreductases ; },
abstract = {All-trans-retinal (atRAL)-induced photoreceptor atrophy and retinal degeneration are hallmark features of dry age-related macular degeneration (AMD) and Stargardt disease type 1 (STGD1). The toxicity of atRAL is closely related to the generation of reactive oxygen species (ROS). Quercetin, a natural product, is known for its potent antioxidant properties; however, its effects in mitigating atRAL-mediated retinal damage remains unclear. This study investigated the protective effects of quercetin against atRAL-induced photoreceptor damage. Using atRAL-loaded 661W photoreceptor cells, we evaluated cell viability, ROS generation, and endoplasmic reticulum (ER) stress under quercetin treatment. Quercetin significantly restored the cell viability (to 70%) and reduced ROS generation in atRAL-treated 661W cells. Additionally, Western blot analysis demonstrated that quercetin mitigated protein kinase RNA-like ER kinase (PERK) signaling, preventing ER stress-induced apoptosis. Importantly, in Abca4[-/-]Rdh8[-/-] mice, an animal model of light-induced atRAL accumulation in the retina, quercetin treatment effectively alleviated light-exposed photoreceptor atrophy and retinal degeneration by attenuating PERK signaling. Thus, quercetin protected photoreceptor cells from atRAL-induced damage by inhibiting ROS generation and PERK signaling, which suggests its potential as a therapeutic agent for atRAL-related retinal degeneration.},
}
@article {pmid39768951,
year = {2024},
author = {Vilkeviciute, A and Pileckaite, E and Bruzaite, A and Cebatoriene, D and Gedvilaite-Vaicechauskiene, G and Kriauciuniene, L and Zaliuniene, D and Liutkeviciene, R},
title = {Evaluating TAB2, IKBKB, and IKBKG Gene Polymorphisms and Serum Protein Levels and Their Association with Age-Related Macular Degeneration and Its Treatment Efficiency.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {12},
pages = {},
pmid = {39768951},
issn = {1648-9144},
support = {S-MIP-23-96//This study was funded by the Research Council of Lithuania under the initiative of Re-searcher Group Projects/ ; },
mesh = {Humans ; Female ; Male ; Aged ; *Macular Degeneration/genetics/blood ; Case-Control Studies ; *I-kappa B Kinase/genetics ; *Polymorphism, Single Nucleotide ; *Adaptor Proteins, Signal Transducing/genetics ; Middle Aged ; Aged, 80 and over ; Treatment Outcome ; Biomarkers/blood/analysis ; Genotype ; },
abstract = {Background and Objectives: Age-related macular degeneration (AMD) is the leading cause of blindness, affecting millions worldwide. Its pathogenesis involves the death of the retinal pigment epithelium (RPE), followed by photoreceptor degeneration. Although AMD is multifactorial, various genetic markers are strongly associated with the disease and may serve as biomarkers for evaluating treatment efficacy. This study investigates TAB2 rs237025, IKBKB rs13278372, and IKBKG rs2472395 variants and their respective serum protein concentrations in relation to AMD occurrence and exudative AMD treatment response to anti-VEGF treatment. Materials and Methods: The case-control study involved 961 individuals, and they were divided into three groups: control, early AMD, and exudative AM patients. Genotyping of selected SNPs were conducted using a real-time polymerase chain reaction method (RT-PCR). Based on the clinical OCT and BCVA data, patients with exudative AMD were categorized into one of two groups: responders and non-responders. The data obtained were analyzed using the "IBM SPSS Statistics 29.0" software program. Results: Our study revealed that TAB2 rs237025 allele A was identified as a risk factor for early and exudative AMD development. The same associations remained only in females with exudative AMD but not in males, suggesting gender-specific pathogenetic pathways in exudative AMD. Analysis of IKBKB rs13278372 or serum IKBKB protein associations with early or exudative AMD occurrence in the Lithuanian population revealed no significant associations. On the other hand, we found that each A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment (OR = 0.347; 95% CI: 0.145-0.961; p = 0.041). These results suggest a potential marker for future studies evaluating anti-VEGF treatment for exudative AMD patients. IKBKG rs2472395 was a protective variant for early AMD in males and for exudative AMD in females only. Also, IKBKG protein concentration was lower in exudative AMD relative to the control group (median (IQR): 0.442 (0.152) vs. 0.538 (0.337), p = 0.015). Moreover, exudative AMD patients who carry the GG genotype of IKBKG rs2472394 exhibited significantly reduced serum IKBKG concentrations compared to the controls (median (IQR): 0.434 (0.199) vs. 0.603 (0.335), p = 0.012), leading to the hypothesis that the IKBKG rs2472394 variant might play a role in protein concentration differences and exudative AMD development. Conclusions: Our study identified the TAB2 rs237025 allele A as a significant risk factor for both early and exudative AMD, with gender-specific associations observed in females with exudative AMD, suggesting distinct pathogenetic pathways. While IKBKB rs13278372 and serum IKBKB protein levels showed no significant association with AMD development, the A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment, indicating its potential as a marker for treatment outcomes. Additionally, the IKBKG rs2472395 variant was found to be protective for early AMD in males and exudative AMD in females, and lower IKBKG protein levels were associated with exudative AMD, particularly in patients with the GG genotype of IKBKG rs2472394, suggesting its role in protein concentration and disease progression. These findings highlight genetic markers that may contribute to AMD pathogenesis and treatment response.},
}
@article {pmid39768916,
year = {2024},
author = {Anitua, E and Muruzabal, F and Recalde, S and Fernandez-Robredo, P and Alkhraisat, MH},
title = {Potential Use of Plasma Rich in Growth Factors in Age-Related Macular Degeneration: Evidence from a Mouse Model.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {12},
pages = {},
pmid = {39768916},
issn = {1648-9144},
support = {ZL-2021/00557//Basque Government/ ; },
mesh = {Animals ; Mice ; *Disease Models, Animal ; *Macular Degeneration/drug therapy ; *Intercellular Signaling Peptides and Proteins/therapeutic use/administration &amp; dosage/pharmacology ; *Iodates ; Intravitreal Injections/methods ; Mice, Inbred C57BL ; Male ; },
abstract = {Background and Objectives: Age-related macular degeneration (AMD) is the leading cause of low vision and legal blindness in adults in developed countries. Wet AMD can be successfully treated using vascular endothelial growth factor (VEGF) inhibitors; however, dry AMD currently has no effective treatment. The purpose of this study is to analyze the efficacy of intraocular injection of plasma rich in growth factors (PRGF) in an AMD mouse model induced by intraperitoneal administration of sodium iodate. Materials and Methods: Intravitreal application of PRGF (experimental group) and saline (control group) was performed immediately after intraperitoneal injection of sodium iodate. Retinographies were performed at 2 and 7 days after treatment administration. The eyes were retrieved for histological and immunohistological analysis. Statistical analysis was performed to compare the outcomes between the study groups. Results: In comparison to saline solution, PRGF significantly decreased the depigmentation of the RPE, showing a more reddened retina. PRGF intravitreal treatment significantly reduced the glial fibrillary acidic protein (GFAP) stained processes, suggesting a significant reduction in the risk of scar formation. Moreover, the myofibroblast invasion into the RPE cell layer was significantly reduced in the PRGF-treated group of mice. There was a tendency for better preservation of the photoreceptors in the PRGF group. Conclusions: Within the limitations of this study, intravitreal injection of PRGF provided significant protection against the degeneration of the photoreceptors and the RPE induced by the systemic administration of NaIO3.},
}
@article {pmid39768839,
year = {2024},
author = {Rusciano, D},
title = {Health Benefits of Epigallocatechin Gallate and Forskolin with a Special Emphasis on Glaucoma and Other Retinal Diseases.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {12},
pages = {},
pmid = {39768839},
issn = {1648-9144},
mesh = {Humans ; Antioxidants/therapeutic use/pharmacology ; *Catechin/analogs &amp; derivatives/therapeutic use/pharmacology ; *Colforsin/therapeutic use/pharmacology ; *Diabetic Retinopathy/drug therapy ; *Glaucoma/drug therapy ; *Macular Degeneration/drug therapy ; Neuroprotective Agents/therapeutic use/pharmacology ; Oxidative Stress/drug effects ; Animals ; },
abstract = {This review highlights the therapeutic potential of epigallocatechin gallate (EGCG) and forskolin in managing retinal diseases, with a focus on glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. EGCG, a potent polyphenol from green tea, exhibits significant antioxidant, anti-inflammatory, and neuroprotective effects, making it a promising candidate for reducing oxidative stress and inflammation in ocular tissues. Forskolin, a diterpene from Coleus forskohlii, increases cyclic AMP (cAMP) levels, which helps lower intraocular pressure (IOP) and provides neuroprotection. Both compounds target critical pathways involved in retinal disease progression, including oxidative stress, mitochondrial dysfunction, and inflammation, offering complementary therapeutic benefits. This review consolidates preclinical and clinical studies, highlighting the potential of EGCG and forskolin as adjunctive or alternative treatments for retinal diseases. Future research should explore the synergistic effects of these compounds, particularly in combination therapies aimed at addressing multiple pathogenic mechanisms in retinal health.},
}
@article {pmid39768707,
year = {2024},
author = {Saßmannshausen, M and Ameln, J and von der Emde, L and Holz, FG and Ach, T and Harmening, WM},
title = {Evaluation of Retinal Sensitivity in Complete Retinal-Pigment-Epithelium and Outer Retinal Atrophy (cRORA) Lesions in Intermediate Age-Related Macular Degeneration (iAMD) by High-Resolution Microperimetry.},
journal = {Journal of clinical medicine},
volume = {13},
number = {24},
pages = {},
pmid = {39768707},
issn = {2077-0383},
support = {HA 5323/6-1//Deutsche Forschungsgemeinschaft/ ; 01EJ2206B//Bundesministerium f&#xfc;r Bildung und Forschung/ ; None//Deutsche Ophthalmologische Gesellschaft/ ; None//Pro Retina - Foundation for the Prevention of Blindness/ ; },
abstract = {Objective: Lesions characterized as complete retinal pigment epithelium and outer retinal atrophy (cRORA) are linked to the progression of intermediate age-related macular degeneration (iAMD). However, the extent of functional impairment of such precursor lesions remains uncertain. Methods: In this cross-sectional study, 4 participants (mean age ± standard deviation: 71.5 ± 2.1 years) underwent extensive multimodal imaging and psychophysical testing of cRORA lesions secondary to iAMD. Lesion-specific functional testing was performed using patient individualized testing grids with clinical conventional available (Stimulus size: 0.43°, ~125 µm) and experimental adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP). One cRORA lesion site and one in-eye control region were tested per patient, respectively. Results: AOSLO imaging revealed an overall decrease in photoreceptor reflectivity, areas of hyporeflectivity over drusen, interspersed with hyperreflective foci, and disrupted photoreceptor mosaic in regions of cRORA. Localized retinal sensitivity assessment with clinical conventional MP yielded an average loss of -14.0 ± 3.3 dB at cRORA lesions compared to the in-eye control regions. In contrast, localized visual impairment assessed by high-resolution AOSLO-MP with smaller test stimuli (20 µm) revealed a sensitivity loss of -15.1 ± 5.1 dB at cRORA lesions (p < 0.01). Notably, also the area surrounding cRORA lesions can be impacted. Conclusions: We demonstrated that cRORA lesions are associated with severe localized functional impairment. cRORA precursor lesions may thus be considered as a surrogate outcome measure in future interventional iAMD trials.},
}
@article {pmid39768611,
year = {2024},
author = {García-Romera, MC and Ponce-García, V and Torres-Parejo, &#xda; and López-Muñoz, A},
title = {Effect of Exposure to Blue Light from Electronic Devices and the Mediterranean Diet on Macular Pigment.},
journal = {Journal of clinical medicine},
volume = {13},
number = {24},
pages = {},
pmid = {39768611},
issn = {2077-0383},
abstract = {Objective: To explore the effect of time exposure to flat screen electronic devices with LED lighting and the Mediterranean diet on macular pigment optical density (MPOD). Methods: In this cross-sectional observational study, the MPOD was measured by heterochromatic flicker photometry in 164 eyes (47 of younger women aged 20-31 and 35 of older women aged 42-70). Exclusion criteria: evidence of macular degeneration and eyes with cataracts. Data on the use of electronic devices and Mediterranean diet adherence were collected through a survey. Nonparametric analysis of variance and independent sample t-tests were used to compare subjects. Results: Significant differences (p < 0.01) were found in total time of exposure to LEDs (hours per day) between both groups (9.31 ± 3.74 younger women vs. 6.33 ± 3.64 older women). The MPOD values for the younger and adult populations were significantly different: 0.38 ± 0.16 and 0.47 ± 0.15 (p < 0.01), respectively. When comparing both groups for the same time of exposure to LEDs, differences were obtained between MPOD values of both populations: For total exposures greater than 6 h per day, the MPOD values were lower in younger women than in adult ones (0.37 ± 0.14 vs. 0.50 ± 0.14, p < 0.01). On the other hand, a significantly higher adherence was found in the older women in comparison with the younger women (OW 9.23 ± 2.50 vs. YW 7.70 ± 2.08, p < 0.01), with higher MPOD values (OW (0.52 ± 0.14) vs. (YW (0.34 ± 0.18). Conclusions: Higher MPOD values are observed with decreasing exposure time to electronic devices with LED lighting screens and higher adherence to the Mediterranean diet.},
}
@article {pmid39768574,
year = {2024},
author = {Mahaling, B and Baruah, N and Dinabandhu, A},
title = {Nanomedicine in Ophthalmology: From Bench to Bedside.},
journal = {Journal of clinical medicine},
volume = {13},
number = {24},
pages = {},
pmid = {39768574},
issn = {2077-0383},
abstract = {Ocular diseases such as cataract, refractive error, age-related macular degeneration, glaucoma, and diabetic retinopathy significantly impact vision and quality of life worldwide. Despite advances in conventional treatments, challenges like limited bioavailability, poor patient compliance, and invasive administration methods hinder their effectiveness. Nanomedicine offers a promising solution by enhancing drug delivery to targeted ocular tissues, enabling sustained release, and improving therapeutic outcomes. This review explores the journey of nanomedicine from bench to bedside, focusing on key nanotechnology platforms, preclinical models, and case studies of successful clinical translation. It addresses critical challenges, including pharmacokinetics, regulatory hurdles, and manufacturing scalability, which must be overcome for successful market entry. Additionally, this review highlights safety considerations, current marketed and FDA-approved nanomedicine products, and emerging trends such as gene therapy and personalized approaches. By providing a comprehensive overview of the current landscape and future directions, this article aims to guide researchers, clinicians, and industry stakeholders in advancing the clinical application of nanomedicine in ophthalmology.},
}
@article {pmid39768274,
year = {2024},
author = {Lee, D and Smith, LEH},
title = {Therapeutic Effects of Taurine and Histidine Supplementation in Retinal Diseases.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {12},
pages = {},
pmid = {39768274},
issn = {2075-1729},
abstract = {Amino acids are basic building blocks of structural proteins and enzymes. They also act as signaling molecules and as fuel. They are characterized as essential if sufficient quantities must be supplied exogenously or as non-essential if they can be endogenously synthesized. Appropriate intake of amino acids not only prevents the development of metabolic diseases but also can reduce the progression of some disease states. Amino acids are strongly associated with retinal metabolism in physiology and pathology. Nonetheless, there is a lack of robust clinical studies supporting the benefits of amino acid supplementation in retinopathy. In this review, we summarize preclinical evidence concerning the potential of supplementing the amino acids taurine and histidine to provide protection against diabetic retinopathy, glaucoma, and age-related macular degeneration. We suggest further directions for studying amino acid-based therapeutic interventions for eye diseases.},
}
@article {pmid39768009,
year = {2024},
author = {Wei, W and Patel, RP and Laponogov, I and Cordeiro, MF and Veselkov, K},
title = {Early Detection of Macular Atrophy Automated Through 2D and 3D Unet Deep Learning.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {12},
pages = {},
pmid = {39768009},
issn = {2306-5354},
abstract = {Macular atrophy (MA) is an irreversible endpoint of age-related macular degeneration (AMD), which is the leading cause of blindness in the world. Early detection is therefore an unmet need. We have developed a novel automated method to identify MA in patients undergoing follow-up with optical coherence tomography (OCT) for AMD based on the combination of 2D and 3D Unet architecture. Our automated detection of MA relies on specific structural changes in OCT, including six established atrophy-associated lesions. Using 1241 volumetric OCTs from 125 eyes (89 patients), the performance of this combination Unet architecture is extremely encouraging, with a mean dice similarity coefficient score of 0.90 ± 0.14 and a mean F1 score of 0.89 ± 0.14. These promising results have indicated superiority when compared to human graders, with a mean similarity of 0.71 ± 0.27. We believe this deep learning-aided tool would be useful to monitor patients with AMD, enabling the early detection of MA and supporting clinical decisions.},
}
@article {pmid39768004,
year = {2024},
author = {Du, K and Nair, AR and Shah, S and Gadari, A and Vupparaboina, SC and Bollepalli, SC and Sutharahan, S and Sahel, JA and Jana, S and Chhablani, J and Vupparaboina, KK},
title = {Detection of Disease Features on Retinal OCT Scans Using RETFound.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {12},
pages = {},
pmid = {39768004},
issn = {2306-5354},
support = {718740//Research to Prevent Blindness/ ; },
abstract = {Eye diseases such as age-related macular degeneration (AMD) are major causes of irreversible vision loss. Early and accurate detection of these diseases is essential for effective management. Optical coherence tomography (OCT) imaging provides clinicians with in vivo, cross-sectional views of the retina, enabling the identification of key pathological features. However, manual interpretation of OCT scans is labor-intensive and prone to variability, often leading to diagnostic inconsistencies. To address this, we leveraged the RETFound model, a foundation model pretrained on 1.6 million unlabeled retinal OCT images, to automate the classification of key disease signatures on OCT. We finetuned RETFound and compared its performance with the widely used ResNet-50 model, using single-task and multitask modes. The dataset included 1770 labeled B-scans with various disease features, including subretinal fluid (SRF), intraretinal fluid (IRF), drusen, and pigment epithelial detachment (PED). The performance was evaluated using accuracy and AUC-ROC values, which ranged across models from 0.75 to 0.77 and 0.75 to 0.80, respectively. RETFound models display comparable specificity and sensitivity to ResNet-50 models overall, making it also a promising tool for retinal disease diagnosis. These findings suggest that RETFound may offer improved diagnostic accuracy and interpretability for specific tasks, potentially aiding clinicians in more efficient and reliable OCT image analysis.},
}
@article {pmid39767734,
year = {2024},
author = {Lee, Y and Seo, JH},
title = {The Potential Causal Association of Apolipoprotein A and B and Age-Related Macular Degeneration: A Mendelian Randomisation Study.},
journal = {Biomedicines},
volume = {12},
number = {12},
pages = {},
pmid = {39767734},
issn = {2227-9059},
support = {2022R1C1C1002929//National Research Foundation of Korea/ ; VHSMC24002//Veterans Health Service Medical Centre/ ; },
abstract = {BACKGROUND/OBJECTIVES: Research has suggested a potential relationship between apolipoproteins A (ApoA) and B (ApoB) and age-related macular degeneration (AMD). This study explored the potential causal relationship between ApoA/ApoB levels and AMD/AMD subtypes using two-sample Mendelian randomisation (MR).<br><br>METHODS: We selected 308 single nucleotide polymorphisms (SNPs) for ApoA and 198 SNPs for ApoB from the UK Biobank data. Summary statistics for AMD were collected from the genome-wide association study of the FinnGen project. We performed two-sample MR to assess the causal effects of ApoA/ApoB on AMD and its subtypes. Potential confounders, including body mass index, C-reactive protein level, and smoking status, were assessed using a multivariable MR analysis.<br><br>RESULTS: ApoA showed a significant causal association with AMD (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.05-1.25, p = 0.003) and was linked to both dry (p = 0.004) and wet (p = 0.025) AMD. ApoB showed a decreasing trend in dry AMD risk (p = 0.074), though not significant, and was not associated with overall or wet AMD. The multivariable MR analysis showed no significant association of ApoA with any AMD subtype (p > 0.05). ApoB decreased dry AMD risk (OR = 0.89, 95% CI = 0.80-0.99, p = 0.039), with trends for overall and wet AMD that were not significant (p = 0.070 and p = 0.091, respectively).<br><br>CONCLUSIONS: These findings suggest that ApoB is associated with lower AMD risk, particularly for dry AMD. Further research is needed to clarify lipid biomarker's role as AMD risk factors.},
}
@article {pmid39767587,
year = {2024},
author = {Ma, DJ and Oh, BL and Bak, E and Kim, JS and Lee, J and Choi, HJ},
title = {A Comprehensive Health Screening Program Reveals the Prevalence of and Risk Factors for Age-Related Macular Degeneration: A Cross-Sectional Analysis.},
journal = {Biomedicines},
volume = {12},
number = {12},
pages = {},
pmid = {39767587},
issn = {2227-9059},
support = {RS-2024-00342696//Ministry of Science and ICT/ ; },
abstract = {Background/Objectives: We investigated the prevalence of age-related macular degeneration (AMD) and associated risk factors in Korean subjects who underwent comprehensive health screening examinations. Methods: This single health screening center-based cross-sectional study included a total of 73,574 consecutive participants older than 30 years who underwent a health screening examination, including fundus photography, between October 2003 and December 2010. Weighted prevalence and risk factors for AMD were evaluated. Logistic regression was used to identify AMD risk factors. Results: The weighted prevalence of AMD was 15.42%, with a prevalence of 3.34% among people in their 30s. Advanced age significantly increased the risk for both early/intermediate AMD (p < 0.001 across the age groups of 40, 50, 60, and 70+ years) and advanced AMD (p <0.001 for the age groups of 60 and 70+ years). The male sex was strongly associated with an increased risk of both early/intermediate and advanced AMD (p < 0.001 for both). Retinal arteriosclerosis, whether low- or high-grade, was linked to early/intermediate AMD (p < 0.001 for both grades), whereas only high-grade arteriosclerosis was linked to advanced AMD (p < 0.001). Additionally, hypertension (p < 0.001), the hepatitis B carrier status (p < 0.001), elevated mean corpuscular volume (p < 0.001), and lower serum uric acid levels (p = 0.014) were associated with early/intermediate AMD. Higher education levels protected against early/intermediate AMD (p = 0.004 for high school graduates, p < 0.001 for ≥college graduates). Higher serum inorganic phosphate levels (p = 0.002) and lower total serum ALB levels (p = 0.005) were significant risk factors for advanced AMD. Conclusions: Korean individuals as young as 30 years old are at risk of AMD. This study newly identified associations between retinal arteriosclerosis and both early/intermediate and advanced AMD, as well as associations between serum inorganic phosphate levels and total ALB levels with advanced AMD.},
}
@article {pmid39767576,
year = {2024},
author = {Nazari, AR and Gresseau, L and Habelrih, T and Zia, A and Lahaie, I and Er-Reguyeg, Y and Coté, F and Annabi, B and Rivard, A and Chemtob, S and Desjarlais, M},
title = {Age-Related Choroidal Involution Is Associated with the Senescence of Endothelial Progenitor Cells in the Choroid.},
journal = {Biomedicines},
volume = {12},
number = {12},
pages = {},
pmid = {39767576},
issn = {2227-9059},
support = {MOP12532/CAPMC/CIHR/Canada ; },
abstract = {Background: Choroidal involution is a common feature of age-related ischemic retinopathies such as age-related macular degeneration (AMD). It is now well recognized that endothelial progenitor cells (EPCs) are essential to endothelial repair processes and in maintaining vascular integrity. However, the contribution of EPCs and the role of senescence in age-related choroidal vascular degeneration remain to be investigated. In this study, we compared the senescent phenotype of EPCs in the choroid and performed whole-genome profiling of EPCs derived from young versus old rats. Methods and Results: We isolated and compared the retinas of young (6-weeks-old) and old (16-18-month-old) rats. The thickness of the choroid and outer nuclear layer (ONL), along with local quantification of CD34+ EPCs, was performed. Compared to young rats, older rats displayed a significant reduction in choroidal and ONL thickness associated with markedly fewer choroid-localized EPCs; this was attested by lower expression of several EPC markers (CXCR4, CD34, CD117, CD133, and KLF-2). Choroid and choroid-localized EPCs displayed abundant senescence as revealed by increased β-gal and P53 expression and decreased Lamin-B1 (immunostaining and RT-qPCR). Concordantly, choroidal cells and EPCs isolated from older rats were unable to form vascular networks ex vivo. To better understand the potential mechanisms associated with the dysfunctional EPCs linked to age-related choroidal involution, we performed whole-genome profiling (mRNA and miRNA) of EPCs derived from old and young rats using next-generation sequencing (NGS); 802 genes were significantly modulated in old vs. young EPCs, corresponding to ~2% of total genes expressed. Using a bioinformatic algorithm, the KEGG pathways suggested that these genes participate in the modulation of several key signaling processes including inflammation, G protein-coupled receptors, and hematopoietic cell lineages. Moreover, we identified 13 miRNAs involved in the regulation of immune system processes, cell cycle arrest and senescence, which are significantly modulated in EPCs from old rats compared to young ones. Conclusions: Our results suggest that age-related choroidal involution is associated with fewer EPCs, albeit displaying a senescence-like phenotype. One would be tempted to propose that biological modification of native EPCs (such as with senolytic agents) could potentially provide a new strategy to preserve the vascular integrity of the aged choroid, and evade progression to degenerative maculopathies.},
}
@article {pmid39767228,
year = {2024},
author = {Gawęcki, M and Kiciński, K and Kucharczuk, J and Teper, S and Hubert, M and Kuc, T},
title = {Ultra-Wide-Field OCT Measurements in Patients with Age-Related Macular Degeneration in Relation to Their Visual Function.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {24},
pages = {},
pmid = {39767228},
issn = {2075-4418},
abstract = {BACKGROUND: Ultra-wide-field optical coherence tomography (UWF-OCT) devices have recently been introduced to clinical practice. The goal of this study was to compare choroidal and retinal thickness (CT and RT) in age-related macular degeneration (AMD) with a healthy control group using UWF-OCT Xephilio S1. Additionally, we sought to determine the relationship between the RT and CT of patients with AMD, measured in different sectors, and their visual acuity.<br><br>METHODS: The study included 104 eyes from 74 participants with dry AMD, 119 eyes from 86 participants with wet AMD, and 85 eyes from 53 healthy controls. Of the participants with wet AMD, 87 eyes received anti-VEGF treatment, 13 were treatment na&#xef;ve, and 19 had incomplete data. The analyzed measurements were taken in the central area of 3 mm in diameter and two peripheral rings located between 3-9 mm and 9-18 mm diameters.<br><br>RESULTS: There was no significant variation in the RT in any sector between the three study groups. CT in dry and wet AMD cohorts was significantly lower compared to controls in every sector. Patients with treatment-na&#xef;ve wet AMD did not demonstrate significant CT loss but had a tendency for lower CT values. Visual impairment in patients with AMD correlated with older age in both subgroups and with smaller RT in the dry AMD subgroup.<br><br>CONCLUSIONS: Values of RT and CT obtained at the mid- and far-periphery with UWF-OCT generally reflect the alterations observed in AMD in the central part of the posterior pole. Intravitreal anti-VEGF treatment might contribute to loss of choroidal tissue observed in AMD in every sector.},
}
@article {pmid39767197,
year = {2024},
author = {Yusufoğlu, E and Fırat, H and Üzen, H and Özçelik, STA and Çiçek, &#x130;B and Şengür, A and Atila, O and Guldemir, NH},
title = {A Comprehensive CNN Model for Age-Related Macular Degeneration Classification Using OCT: Integrating Inception Modules, SE Blocks, and ConvMixer.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {24},
pages = {},
pmid = {39767197},
issn = {2075-4418},
support = {TEKF.24.47//F&#x131;rat University/ ; },
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a significant cause of vision loss in older adults, often progressing without early noticeable symptoms. Deep learning (DL) models, particularly convolutional neural networks (CNNs), demonstrate potential in accurately diagnosing and classifying AMD using medical imaging technologies like optical coherence to-mography (OCT) scans. This study introduces a novel CNN-based DL method for AMD diagnosis, aiming to enhance computational efficiency and classification accuracy. Methods: The proposed method (PM) combines modified Inception modules, Depthwise Squeeze-and-Excitation Blocks, and ConvMixer architecture. Its effectiveness was evaluated on two datasets: a private dataset with 2316 images and the public Noor dataset. Key performance metrics, including accuracy, precision, recall, and F1 score, were calculated to assess the method's diagnostic performance. Results: On the private dataset, the PM achieved outstanding performance: 97.98% accuracy, 97.95% precision, 97.77% recall, and 97.86% F1 score. When tested on the public Noor dataset, the method reached 100% across all evaluation metrics, outperforming existing DL approaches. Conclusions: These results highlight the promising role of AI-based systems in AMD diagnosis, of-fering advanced feature extraction capabilities that can potentially enable early detection and in-tervention, ultimately improving patient care and outcomes. While the proposed model demon-strates promising performance on the datasets tested, the study is limited by the size and diversity of the datasets. Future work will focus on external clinical validation to address these limita-tions.},
}
@article {pmid39765886,
year = {2024},
author = {Li, X and Zhao, L and Zhang, B and Wang, S},
title = {Berries and Their Active Compounds in Prevention of Age-Related Macular Degeneration.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
pmid = {39765886},
issn = {2076-3921},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, significantly diminishing quality of life. Currently, there is no available treatment to reverse retinal degeneration and neuronal loss, prompting a focus on interventions that slow the progression of intermediate AMD and geographic atrophy. Berries are rich in bioactive compounds, including flavonoids, anthocyanins, carotenoids, and resveratrol, known for their antioxidant, anti-inflammatory, and anti-angiogenic properties. Preclinical studies suggest that extracts from various berries, such as aronia, honeysuckle, black currant, goji, and bilberry, can improve retinal health by reducing oxidative stress and inflammation. Although clinical trials are limited, emerging evidence indicates that dietary intake of these compounds may enhance visual function and slow the progression of AMD. This review summarizes findings from both animal studies and clinical trials to identify specific berries that have been validated to prevent or delay AMD progression, as well as those with potential therapeutic value. Furthermore, we examine the key phytochemicals present in these berries, their mechanisms of action on macular degeneration, and their distinct properties for therapeutic application. A deeper understanding of these characteristics could enable the rational appliance of berries, especially wolfberry, and berry-derived components, such as carotenoids and anthocyanins, to optimize better therapeutic outcomes in AMD management.},
}
@article {pmid39764334,
year = {2024},
author = {Goel, A and Das, M and Sen, S},
title = {Comparative Analysis of Patient-Reported Outcome Measures in Manual Small-Incision Cataract Surgery Versus Phacoemulsification for Brown Cataracts.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e75260},
pmid = {39764334},
issn = {2168-8184},
abstract = {Objective The objective of this study is to compare patient-reported outcome measures using the Catquest Questionnaire in patients undergoing phacoemulsification (Phaco) versus manual small-incision cataract surgery (MSICS). Materials and methods This descriptive cross-sectional study included patients aged 40 years and older with cataracts classified as nuclear sclerosis (NS) grade 3 or higher. Demographic details were recorded and a comprehensive ophthalmological exam was done. All patients were operated on by the same surgeon, with 41 undergoing MSICS and 40 undergoing Phaco. Monofocal intraocular lenses were implanted in all cases. Responses to the Catquest questionnaire were collected preoperatively and at six weeks postoperatively. The questionnaire, validated in the Odia language, was provided to patients in both Odia and English. Results Out of 81 patients, 32 underwent their first eye surgery while 49 had their second eye surgery. Both Phaco and MSICS procedures showed significant visual acuity improvement. Mean visual acuity improved from 1.19 to 0.37 in the right eye and from 0.74 to 0.35 in the left eye, with p-values <0.001. Nearly all patients experienced better near vision postoperatively, with 45 (97.8%) of right eyes and 34 (100%) of left eyes achieving near vision between N6 and N8. One Phaco patient with age-related macular degeneration had near vision limited to N10. In a few areas, such as carrying out hobbies, doing needlework, and overall vision satisfaction, patients in the MSICS group patients did better than Phaco group. Response to other questions showed similar responses in both the Phaco and MSICS groups. Conclusion Cataract surgery irrespective of procedure improves overall vision-specific functioning and quality of life. MSICS is often preferred over Phaco for its speed, cost-effectiveness, and lower technological dependence, especially for brown cataracts and bulk surgeries. The choice between MSICS and Phaco should depend on patient needs, preoperative counseling, surgeon expertise, and resources.},
}
@article {pmid39764103,
year = {2024},
author = {Alibhai, AY and Moult, E and Jamil, MU and Raza, K and Morales, MU and Ribiero, R and Baumal, CR and Fujimoto, JG and Waheed, NK},
title = {Evaluating the Reliability of a Microperimetry-Based Method for Assessing Visual Function in the Junctional Zone of Geographic Atrophy Lesions.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {39764103},
issn = {2693-5015},
support = {R01 EY011289/EY/NEI NIH HHS/United States ; R01 EY034080/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.<br><br>METHODS: A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10-2 fovea centered grid was performed at baseline and follow-up visits. GA regions were traced on fundus autofluorescence (FAF) images. Two graders independently registered baseline microperimetry images with baseline FAF images in a sampling of 30 eyes from the OAKS study. Agreement between the two graders' assessments of mean sensitivity and the number of scotomatous points within a &#xb1;250 &#x3bc;m GA junctional zone was assessed.<br><br>RESULTS: The intraclass correlation (ICC) and coefficient of repeatability (CoR) for the mean junctional zone sensitivity were 0.994 and 0.349 dB, respectively. The ICC and CoR for the total number of scotomatous points within the junctional zone were 0.997 and 0.218, respectively.<br><br>CONCLUSIONS: The repeatability of the methodology and its compatibility with standard MP acquisitions appear to make it well-suited for identifying and analyzing retinal sensitivity within high-risk areas of the retina.},
}
@article {pmid39763327,
year = {2025},
author = {Beretta, F and Sacconi, R and Querques, L and Prascina, F and Zucchiatti, I and Bandello, F and Querques, G},
title = {"Triple and Plan" (TriPla) regimen for long lasting new generation intravitreal anti-VEGF.},
journal = {European journal of ophthalmology},
volume = {35},
number = {3},
pages = {779-784},
doi = {10.1177/11206721241310262},
pmid = {39763327},
issn = {1724-6016},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; COVID-19/epidemiology ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Recombinant Fusion Proteins/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy ; },
abstract = {Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) medications are the primary treatment for neovascular age-related macular degeneration (nAMD). However, frequent administrations pose significant burdens on patients, healthcare providers, and systems. The treat-and-extend (T&amp;E) regimen, which adjusts treatment intervals based on patient response, aims to reduce injection frequency while maintaining disease control. The "Triple and Plan" (TriPla) regimen, developed during the COVID-19 pandemic, further optimizes treatment by scheduling three consecutive injections, thus minimizing clinic visits while ensuring adequate treatment.Newer agents such as Faricimab, Aflibercept 8 mg, and Brolucizumab offer longer-lasting effects, potentially extending treatment intervals. Faricimab, targeting both Ang-2 and VEGF-A, requires fewer injections and visits under the TriPla regimen compared to traditional T&amp;E. Aflibercept 8 mg, with its higher concentration, promises extended intervals up to 16 weeks, reducing the injection frequency. Brolucizumab, notable for its small size and effective tissue penetration, also offers prolonged therapeutic effects but requires careful monitoring due to potential adverse events.In the first two years of treatment, patients using the TriPla regimen with these new drugs would undergo a slightly higher number of injections but with fewer clinic visits compared to the T&amp;E regimen. The TriPla approach optimizes scheduling and reduces the workload on specialists, potentially improving patient care and healthcare system efficiency. These advancements in treatment regimens and drug formulations present significant benefits in managing nAMD, balancing effective disease control with reduced healthcare burdens.},
}
@article {pmid39762563,
year = {2025},
author = {Giuliani, M and Uboldi, C and Dellatorre, FG and Latour, E and Ponce, NMA and Stortz, CA and Lassalle, VL and Ayala-Peña, VB},
title = {Undaria pinnatifida fucoidan extract inhibits activation of the NF-κB signaling pathway by herpes simplex virus type 1 and prevents amyloid-β peptide synthesis in retinal pigment epithelium cells.},
journal = {Archives of virology},
volume = {170},
number = {2},
pages = {27},
pmid = {39762563},
issn = {1432-8798},
mesh = {*Retinal Pigment Epithelium/drug effects/virology/metabolism ; *Amyloid beta-Peptides/metabolism ; *Polysaccharides/pharmacology ; *Undaria/chemistry ; *Signal Transduction/drug effects ; *NF-kappa B/metabolism ; *Herpesvirus 1, Human/drug effects/physiology ; Humans ; Animals ; Plant Extracts/pharmacology ; Antiviral Agents/pharmacology ; Cell Line ; Antioxidants/pharmacology ; Epithelial Cells/drug effects/virology/metabolism ; Oxidative Stress/drug effects ; Edible Seaweeds ; },
abstract = {Neurodegenerative pathologies such as age-related macular degeneration currently have no cure or effective treatment. In this type of disease, the presence of amyloid-β peptides, oxidative stress, and inflammation trigger dysregulation of retinal pigment epithelial cells and progression toward the death of these cells, resulting in a loss of vision. The production of amyloid-β peptides, oxidative stress, and inflammation can be triggered in response to viral infections. Fucoidans are sulfated polysaccharides that are present in the cell walls of brown algae. There is a large body of literature reporting a wide range of biological properties of these compounds. In this study, we investigated whether Undaria pinnatifida fucoidan extract can prevent infection with herpes simplex virus type 1 and if the extract has antioxidant activity. We also evaluated whether, under viral infection conditions, the synthesis of amyloid-β peptide and NF-κB activation could be inhibited by the extract. The results showed for the first time that this extract can prevent viral infection in retinal pigment epithelial cells and that they can prevent the formation of amyloid-β peptide and the activation of the NF-κB pathway during viral infection. We also found that Undaria pinnatifida fucoidan extract has antioxidant activity and reduces the levels of reactive oxygen species. These data suggest that Undaria pinnatifida fucoidan extract might be effective for treating diseases triggered by viral infections, such as degenerative retinal diseases.},
}
@article {pmid39762260,
year = {2025},
author = {Han, HY and Park, SM and Lee, JH and Kim, CG and Kim, JW and Cho, HJ and Kim, JH},
title = {Outcomes and predictive factors for fluid resolution following three loading injections of faricimab for treatment-naïve neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {938},
pmid = {39762260},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; Aged ; Retrospective Studies ; Aged, 80 and over ; *Subretinal Fluid/metabolism ; Treatment Outcome ; *Visual Acuity/drug effects ; Intravitreal Injections ; Macular Degeneration/drug therapy/pathology ; Middle Aged ; Wet Macular Degeneration/drug therapy ; Tomography, Optical Coherence ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; },
abstract = {To evaluate the outcomes and predictive factors for fluid resolution following three loading injections of faricimab for neovascular age-related macular degeneration(AMD). This retrospective study included patients diagnosed with treatment-naïve neovascular AMD who received three monthly injections of faricimab. Changes in best-corrected visual acuity(BCVA) and central retinal thickness(CRT) following treatment were evaluated. The resolution of subretinal fluid(SRF), intraretinal fluid(IRF), and serous pigment epithelial detachment(PED) was also assessed. In addition, factors associated with complete resolution of SRF and IRF were investigated. A total of 69 patients were included in this study. BCVA significantly improved from a mean logarithm of minimal angle of resolution of 0.64 ± 0.41 at baseline to 0.47 ± 0.39 at 3 months (P < 0.001). CRT significantly decreased from 424.1 ± 155.5 μm at baseline to 266.3 ± 71.7 μm at 3 months (P < 0.001). At baseline, SRF was observed in 55 eyes (79.7%), IRF in 39 eyes(56.5%), and serous PED in 57 eyes(82.6%). By 3 months, the number of eyes showing these findings had decreased to 11 eyes(15.9%) for SRF, 6 eyes(8.7%) for IRF, and 10 eyes(14.5%) for serous PED. The presence of type 2 (88.2%) and type 3 (94.7%) macular neovascularization(MNV) was associated with a high incidence of complete resolution of SRF and IRF after treatment. Three loading injections of faricimab resulted in significant functional and anatomical improvements in treatment-naïve neovascular AMD, with a high rate of resolution of SRF, IRF, and serous PED. The anatomical effects were especially pronounced in cases of type 2 and type 3 MNV.},
}
@article {pmid39761510,
year = {2025},
author = {Montesel, A and Sen, S and Preston, E and Patel, PJ and Huemer, J and Hamilton, RD and Nicholson, L and Papasavvas, I and Tucker, WR and Yeung, I},
title = {INTRAOCULAR INFLAMMATION ASSOCIATED WITH FARICIMAB THERAPY: One-Year Real-World Outcomes.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {5},
pages = {827-832},
doi = {10.1097/IAE.0000000000004394},
pmid = {39761510},
issn = {1539-2864},
support = {//National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology/ ; },
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Middle Aged ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Endophthalmitis/chemically induced/epidemiology/diagnosis ; Follow-Up Studies ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy ; Incidence ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To report 1-year real-world evidence on intraocular inflammation (IOI) adverse events in patients undergoing faricimab therapy in a tertiary care hospital.<br><br>METHODS: A retrospective review of electronic medical records was conducted for patients receiving faricimab treatment for neovascular age-related macular degeneration and diabetic macular edema at Moorfields Eye Hospital between September 1, 2022, and August 31, 2023. The primary outcome was the incidence of IOI (excluding endophthalmitis).<br><br>RESULTS: Two thousand three hundred and eighteen eyes from 1,860 patients were included and underwent a total of 10,297 injections. A total of 20 eyes (16 patients) had &#x2265;1 adverse event of IOI. Estimated incidence of IOI was 0.19% per injection (95% confidence interval, 0.12-0.30), 0.86% per eye (95% confidence interval 0.53-1.33), and 0.86% per patient (95% confidence interval, 0.49-1.39). Intraocular inflammation mostly occurred within the first injections (median 3.5 injections, range 1-10). All cases presented with anterior uveitis and were associated with vitritis in four eyes (20%). No cases of posterior uveitis or evidence of retinal vascular occlusion were reported. There was no statistically significant difference between the mean visual acuity before and after IOI event (0.40 and 0.378 logarithm of minimum angle of resolution, respectively, P = 0.26).<br><br>CONCLUSION: In this real-world report, faricimab was well tolerated with an incidence of IOI-related adverse events consistent to that observed in registration trials. The adverse events were generally mild and had a favorable prognosis.},
}
@article {pmid39760687,
year = {2025},
author = {Wongchaisuwat, N and Wang, J and Hormel, TT and Jia, Y and White, ES and Rodanant, N and Phasukkijwatana, N},
title = {Slab-Specific Projection-Resolved Optical Coherence Tomography Angiography for Enhancing En Face Polyp Detection in Polypoidal Choroidal Vasculopathy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {66},
number = {1},
pages = {9},
pmid = {39760687},
issn = {1552-5783},
support = {R01 EY023285/EY/NEI NIH HHS/United States ; P30 EY010572/EY/NEI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; R01 EY024544/EY/NEI NIH HHS/United States ; R01 EY031394/EY/NEI NIH HHS/United States ; R01 EY035410/EY/NEI NIH HHS/United States ; R01 EY027833/EY/NEI NIH HHS/United States ; T32 EY023211/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Polyps/diagnosis/diagnostic imaging ; *Fluorescein Angiography/methods ; Female ; Male ; Aged ; *Algorithms ; *Choroid/blood supply/diagnostic imaging ; Indocyanine Green/administration &amp; dosage ; Coloring Agents/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Choroidal Neovascularization/diagnosis/diagnostic imaging ; Fundus Oculi ; Choroid Diseases/diagnosis/diagnostic imaging ; Polypoidal Choroidal Vasculopathy ; },
abstract = {PURPOSE: A projection-resolved optical coherence tomography angiography (PR-OCTA) algorithm with slab-specific strategy was applied in polypoidal choroidal vasculopathy (PCV) to differentiate between polyp and branching vascular network (BVN) and improve polyp detection by en face OCTA.<br><br>METHODS: Twenty-nine participants diagnosed with PCV by indocyanine green angiography (ICGA) and 30 participants diagnosed with typical neovascular age-related macular degeneration (nAMD) were enrolled. Polyps were classified into three categories after using the slab-specific PR algorithm. Type 1 polyps were considered in high-elevated pigment epithelial detachment (PED) and displayed in green. Type 2 polyps were considered in low-elevated PED and encoded in yellow, similar to BVN structures. Type 3 polyps were not able to be detected on OCTA. The algorithms were tested in the nAMD group to differentiate PCV and typical nAMD.<br><br>RESULTS: With the algorithm, type 1 polyps were readily differentiated from BVN on en face OCTA. Polyp detection rate on en face OCTA only (type 1) was 68%, which was significantly improved from 30% when the algorithm was not used (P = 0.0001). To identify type 2 polyps, a combination of en face and cross-sectional OCTA images was needed and this resulted in a 91% polyp detection rate (types 1 and 2). The absence of luminal structure on OCT at the polyp site, small polyp size, and absence of halo on ICGA appeared to influence the polyp detection rate. When applying the algorithm to the nAMD group, 83% were correctly classified as typical nAMD (absence of type 1 polyps), whereas 17% showed false detection of polyps due to flow signals at the apices of large PEDs.<br><br>CONCLUSIONS: The slab-specific PR-OCTA with different color coding provides significant improvement in detecting polyp structures on en face OCTA, leading to rapid coronal visualization and diagnosis of PCV without the risk of dye injection.},
}
@article {pmid39760177,
year = {2025},
author = {Liu, M and Zhao, P and Feng, H and Yang, Y and Zhang, X and Chen, E and Xiao, H and Luo, J and Chen, H and Yin, J and Lin, M and Mao, R and Zhu, X and Li, J and Fei, P},
title = {Biglycan stimulates retinal pathological angiogenesis via up-regulation of CXCL12 expression in pericytes.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {1},
pages = {e70262},
pmid = {39760177},
issn = {1530-6860},
support = {81770963//MOST | National Natural Science Foundation of China (NSFC)/ ; 82371070//MOST | National Natural Science Foundation of China (NSFC)/ ; 2023kflx001//Open Project of Sichuan Provincial Key Laboratory for Human Disease Gene Study/ ; },
mesh = {Animals ; *Pericytes/metabolism ; *Chemokine CXCL12/metabolism/genetics ; Mice ; *Biglycan/metabolism/genetics ; *Up-Regulation ; *Retinal Neovascularization/metabolism/pathology/genetics ; *Mice, Inbred C57BL ; Humans ; Receptors, CXCR4/metabolism/genetics ; Neovascularization, Pathologic/metabolism ; Retina/metabolism/pathology ; Cells, Cultured ; },
abstract = {Retinal pathological angiogenesis (PA) is a common hallmark in proliferative retinopathies, including age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP). The mechanisms underlying PA is complex and incompletely understood. In this study, we investigated the role of extracellular matrix (ECM) protein biglycan (BGN) in PA using an oxygen-induced retinopathy (OIR) mouse model, along with hypoxia (1% O2) conditions for incubating pericytes and endothelial cells in vitro. We found a significant upregulation of Bgn in the retinas of OIR mice. Intravitreal injection of Bgn-specific small interfering RNA (siRNA) in OIR mice at postnatal day 12 (P12) effectively curbed retinal PA at P17. Using cultured cells, we found that BGN expression in pericytes was highly sensitive to hypoxic stimulation compared to endothelial cells. We further showed that BGN stimulated retinal PA via the upregulation of C-X-C motif chemokine ligand 12 (CXCL12). Inhibition of the CXCL12-CXCR4 axis effectively diminished PA in OIR mouse. In conclusion, our study demonstrated the stimulatory role of BGN in retinal PA, identified the link between BGN and CXCL12 expression, and further highlighted the role of pericytes in retinal PA.},
}
@article {pmid39758131,
year = {2025},
author = {Herrera, G and Cheng, Y and Attiku, Y and Hiya, FE and Shen, M and Liu, J and Lu, J and Berni, A and Trivizki, O and Li, J and O'Brien, RC and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Comparison between Spectral-domain and Swept-source OCT Angiography Scans for the Measurement of Hyperreflective Foci in Age-related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100633},
pmid = {39758131},
issn = {2666-9145},
abstract = {PURPOSE: Spectral-domain OCT angiography (SD-OCTA) scans were used in an algorithm developed for swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the measurement of hyperreflective foci (HRF) in intermediate age-related macular degeneration (iAMD).<br><br>DESIGN: Retrospective study.<br><br>PARTICIPANTS: Forty eyes from 35 patients with iAMD.<br><br>METHODS: Patients underwent SD-OCTA and SS-OCTA imaging at the same visit using a 6&#xa0;&#xd7;&#xa0;6 mm OCTA scan pattern. Hyperreflective foci were detected as hypotransmission defects on en face structural images generated from a custom slab positioned 64 to 400 &#x3bc;m beneath Bruch's membrane and confirmed on corresponding B-scans by the presence of well circumscribed lesions within the neurosensory retina or along the retinal pigment epithelium (RPE) that are of equal or greater reflectivity than that of the RPE. Two independent graders evaluated the en face images and B-scans for the presence of these lesions. Outlines of HRF on en face images were generated using a published semiautomated algorithm developed for SS-OCTA scans and manually corrected by the graders when necessary. The total area measurements of the HRF within the 5-mm circle centered on the fovea were obtained from the algorithm using each imaging method.<br><br>MAIN OUTCOME MEASURES: Agreement of the square root (sqrt) of the HRF total areas obtained from SS-OCTA and SD-OCTA.<br><br>RESULTS: The sqrt total areas of the HRF from both imaging modalities were highly concordant, with Lin's concordance correlation coefficient (rc) of 0.94 (95% confidence interval: 0.86-0.97; P&#xa0;<&#xa0;0.001). The mean sqrt of the total HRF area measurements identified using SS-OCTA and SD-OCTA imaging were 0.390 mm (standard deviation [SD]: 0.170) and 0.393 mm (SD: 0.187), respectively with mean difference of&#xa0;-0.003 (95% confidence interval:&#xa0;-0.021 to 0.015; P=0.76).<br><br>CONCLUSIONS: Spectral-domain OCT angiography scans yielded results similar to SS-OCTA scans when the same semiautomated algorithm was used to measure HRF in the central 5 mm of the macula, suggesting that either a single 6&#xa0;&#xd7;&#xa0;6 mm SD-OCTA or a SS-OCTA scan pattern can be used to determine the total macular HRF burden in eyes with age-related macular degeneration.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39758130,
year = {2025},
author = {Salvi, A and Cluceru, J and Gao, SS and Rabe, C and Schiffman, C and Yang, Q and Lee, AY and Keane, PA and Sadda, SR and Holz, FG and Ferrara, D and Anegondi, N},
title = {Deep Learning to Predict the Future Growth of Geographic Atrophy from Fundus Autofluorescence.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100635},
pmid = {39758130},
issn = {2666-9145},
abstract = {PURPOSE: The region of growth (ROG) of geographic atrophy (GA) throughout the macular area has an impact on visual outcomes. Here, we developed multiple deep learning models to predict the 1-year ROG of GA lesions using fundus autofluorescence (FAF) images.<br><br>DESIGN: In this retrospective analysis, 3 types of models were developed using FAF images collected 6 months after baseline to predict the GA lesion area (segmented lesion mask) at 1.5 years, FAF images collected at baseline and 6 months to predict the GA lesion at 1.5 years, and FAF images collected 6 months after baseline to predict the GA lesion at 1 and 1.5 years. The 1-year ROG from the 6-month visit was derived by taking the difference between the GA lesion area (segmented lesion mask) at the 1.5-year and 6-month visits.<br><br>PARTICIPANTS: Patients enrolled in the following lampalizumab clinical trials and prospective observational studies: NCT02247479, NCT02247531, NCT02479386, and NCT02399072.<br><br>METHODS: Datasets of study eyes from 597 patients were split into model training (310), validation (78), and test sets (209), stratified by baseline or initial lesion area, lesion growth rate, foveal involvement, and focality. Deep learning experiments were performed using the 2-dimensional U-Net; whole-lesion and multiclass models were developed.<br><br>MAIN OUTCOME MEASURES: The performance of the models was evaluated by calculating the Dice score, coefficient of determination (R[2]), and the squared Pearson correlation coefficient (r[2]) between the true and derived GA lesion 1-year ROG.<br><br>RESULTS: The model using baseline and 6-month FAF images to predict GA lesion enlargement at 1.5 years had the best performance for the derived 1-year ROG. Mean Dice scores were 0.73, 0.68, and 0.70 in the training, validation, and test sets, respectively. The R[2] (0.77, 0.53, and 0.79) and r[2] (0.83, 0.61, and 0.79) showed similar trends across the 3 sets.<br><br>CONCLUSIONS: These findings show the potential of using baseline and/or 6-month visit FAF images to predict 1-year GA ROG using a deep learning approach. This work could potentially help support decision-making in clinical trials and more informed treatment decisions in clinical practice.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39757986,
year = {2025},
author = {Zhang, J and Yang, H and Li, L and Hu, S and Liu, Y and Li, S and Wu, L and He, T},
title = {Genetic evidence supports the causal effects of exposure to ambient air pollution on autoimmune eye diseases.},
journal = {International journal of environmental health research},
volume = {35},
number = {9},
pages = {2506-2519},
doi = {10.1080/09603123.2025.2449968},
pmid = {39757986},
issn = {1369-1619},
mesh = {Humans ; *Air Pollution/adverse effects ; *Autoimmune Diseases/genetics/epidemiology/chemically induced ; Particulate Matter/adverse effects/analysis ; *Air Pollutants/adverse effects/analysis ; Mendelian Randomization Analysis ; *Environmental Exposure/adverse effects ; *Eye Diseases/genetics/epidemiology/chemically induced ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; },
abstract = {Previous observational studies have reported inconsistent associations between air pollution and autoimmune eye diseases (AEDs). The primary objective of this Mendelian randomization (MR) study was to investigate the causal link of air pollution with AEDs risk. The instrumental variables were selected based on genome-wide association study data. Univariable and multivariable MR analyses were conducted to disentangle the causality of air pollutants with AEDs. The estimates of univariable MR analysis revealed a suggestively causal link between NO2 or NOx exposure and diabetic retinopathy (OR=1.29, 95% CI=1.05-1.58, P=0.015; OR=1.33, 95% CI=1.05-1.69, P=0.019, respectively). A suggestive association was observed between PM2.5 exposure and age-related macular degeneration (OR=1.46, 95% CI=1.09-1.97, P=0.013). In addition, multivariable MR indicated that the observed association was remained consistent and robust. Rigorous sensitivity analyses confirmed the robustness and consistency of these findings. Our study firstly provided the genetic evidence linking air pollution, specially NO2, NOx and PM2.5, to AEDs susceptibility.},
}
@article {pmid39757747,
year = {2025},
author = {Papadam, A and Lionikas, A and Grassmann, F},
title = {Differential Organ Ageing Is Associated With Age-Related Macular Degeneration.},
journal = {Aging cell},
volume = {24},
number = {5},
pages = {e14473},
pmid = {39757747},
issn = {1474-9726},
mesh = {Humans ; *Macular Degeneration/genetics/pathology ; Male ; Female ; Aged ; *Aging/genetics ; Middle Aged ; Risk Factors ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is a progressive disorder and the leading cause of central vision loss. Age is the most important risk factor, followed by genetics and smoking. However, ageing is a complex process, and biological age can deviate from chronological age between individuals and within different organ systems. Initially, we used machine learning to predict the biological age of the immune, cardiovascular, pulmonary, renal, musculoskeletal, metabolic and hepatic systems by analysing various physiological and physical markers in the UK Biobank cohort. Then, we investigated the association of each organ's biological age with incident AMD derived from electronic health record data as well as with different AMD genetic risk scores. We observed that most organ systems in participants who developed AMD after recruitment showed accelerated ageing compared with controls, with the immune system being the most affected, especially in younger males. Surprisingly, we found that AMD patients showed slower ageing of their hepatic system compared to controls, particularly in female patients. The overall AMD genetic risk score was associated with faster organ ageing across all tissues except cardiovascular and pulmonary, while genetic risk scores stratified by pathways differently influenced each organ system. In conclusion, we found differential organ ageing associated with AMD. Significantly, genetic risk variants of AMD are associated with differential ageing of various organ systems.},
}
@article {pmid39756898,
year = {2025},
author = {Hata, M},
title = {[Past history of obesity and immune memory in age-related macular degeneration].},
journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica},
volume = {160},
number = {1},
pages = {23-25},
doi = {10.1254/fpj.24069},
pmid = {39756898},
issn = {0015-5691},
mesh = {*Macular Degeneration/immunology ; Humans ; *Obesity/immunology ; *Immunologic Memory ; Animals ; Immunity, Innate ; Complement Factor H/genetics ; },
abstract = {Age-related macular degeneration (AMD) is one of the most common neuroinflammatory diseases that is the leading cause of blindness worldwide. AMD is caused by not only mutations in immune-related genes such as Cfh (complement factor H) but also the accumulation of environmental factors such as obesity and other inflammatory triggers with age. Our study found that the past histories of obesity can lead to immunological reprogramming in the innate immune system and affect the development of AMD in later life. This reveals a new link in the role of innate immune memory in neuroinflammatory diseases such as AMD, and intervention in innate immune memory may be a new therapeutic strategy.},
}
@article {pmid39756691,
year = {2025},
author = {Chen, JS and Esko, JD and Walker, E and Gordts, PLSM and Baxter, SL and Toomey, CB},
title = {High-Density Lipoproteins Associated with Age-Related Macular Degeneration in the All of Us Research Program.},
journal = {Ophthalmology},
volume = {132},
number = {6},
pages = {684-691},
pmid = {39756691},
issn = {1549-4713},
support = {K08 EY035322/EY/NEI NIH HHS/United States ; OT2 OD026556/OD/NIH HHS/United States ; DP5 OD029610/OD/NIH HHS/United States ; U2C OD023196/OD/NIH HHS/United States ; OT2 OD026551/OD/NIH HHS/United States ; U24 OD023121/OD/NIH HHS/United States ; OT2 OD026552/OD/NIH HHS/United States ; OT2 OD026549/OD/NIH HHS/United States ; OT2 OD025337/OD/NIH HHS/United States ; T15 LM011271/LM/NLM NIH HHS/United States ; OT2 OD025277/OD/NIH HHS/United States ; OT2 OD026550/OD/NIH HHS/United States ; OT2 OD026553/OD/NIH HHS/United States ; OT2 OD023205/OD/NIH HHS/United States ; OT2 OD025276/OD/NIH HHS/United States ; P01 HL131474/HL/NHLBI NIH HHS/United States ; OT2 OD026557/OD/NIH HHS/United States ; OT2 OD026554/OD/NIH HHS/United States ; U24 OD023163/OD/NIH HHS/United States ; OT2 OD023206/OD/NIH HHS/United States ; U24 OD023176/OD/NIH HHS/United States ; OT2 OD026548/OD/NIH HHS/United States ; P30 EY022589/EY/NEI NIH HHS/United States ; OT2 OD025315/OD/NIH HHS/United States ; K12 EY024225/EY/NEI NIH HHS/United States ; OT2 OD026555/OD/NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Retrospective Studies ; Aged ; *Macular Degeneration/blood/genetics/epidemiology ; United States/epidemiology ; Polymorphism, Single Nucleotide ; *Lipoproteins, HDL/blood/genetics ; Risk Factors ; Middle Aged ; Aged, 80 and over ; Triglycerides/blood ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Odds Ratio ; },
abstract = {PURPOSE: Extracellular lipoprotein aggregation is a critical event in age-related macular degeneration (AMD) pathogenesis. In this study, we sought to analyze associations between clinical and genetic-based factors related to lipoprotein metabolism and risk for AMD in the All of Us research program.<br><br>DESIGN: Cross-sectional retrospective data analysis.<br><br>PARTICIPANTS: A total of 5028 healthy participants and 2328 patients with AMD from All of Us.<br><br>METHODS: Participants with and without AMD were age, race, and sex matched in a 1:2 ratio, respectively. Smoking status, history of hyperlipidemia, and statin use were extracted in a binary manner. Statin use was further subcategorized into hepatically versus nonhepatically metabolized statins. Laboratory values for low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TGs) were also extracted, and outliers were excluded from analysis. The PLINK toolkit was used to extract single nucleotide polymorphisms (SNPs) associated with LDL and HDL dysregulation, as published in prior work. Odds ratio curves were computed to assess the risk between LDL, TG, and HDL versus AMD. All clinical and genetic variables were input into a multivariable logistic regression model, and odds ratios and P values were generated.<br><br>MAIN OUTCOME MEASURES: Statistical significance of risk factors for AMD, thresholded at P &#x2264; 0.05.<br><br>RESULTS: On multivariable regression analysis, statin use and low and high HDL were significantly associated with increased AMD risk (P < 0.001 for all variables). Additionally, the multivariable regression implicated HDL-associated SNP's increased risk for AMD. Last, LPA was identified (P = 0.007) as a novel SNP associated with increased AMD risk.<br><br>CONCLUSIONS: There exists a U-shaped relationship between HDL and AMD risk, such that high and low HDL are significantly associated with increased AMD risk. Additionally, SNPs associated with HDL metabolism are associated with AMD risk. This analysis further establishes the role of HDL in AMD pathogenesis.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39756006,
year = {2025},
author = {Muniyandi, A and Hartman, GD and Sishtla, K and Rai, R and Gomes, C and Day, K and Song, Y and Masters, AR and Quinney, SK and Qi, X and Woods, H and Boulton, ME and Meyer, JS and Vilseck, JZ and Georgiadis, MM and Kelley, MR and Corson, TW},
title = {Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.},
journal = {Angiogenesis},
volume = {28},
number = {1},
pages = {11},
pmid = {39756006},
issn = {1573-7209},
support = {F31EY035171/EY/NEI NIH HHS/United States ; U01 CA274304/CA/NCI NIH HHS/United States ; R01HL140961/HL/NHLBI NIH HHS/United States ; P30CA082709/CA/NCI NIH HHS/United States ; F31 EY035171/EY/NEI NIH HHS/United States ; R01EY031939/EY/NEI NIH HHS/United States ; R01 CA282478/CA/NCI NIH HHS/United States ; R35 GM146888/GM/NIGMS NIH HHS/United States ; P30 CA082709/CA/NCI NIH HHS/United States ; R01 CA254110/CA/NCI NIH HHS/United States ; R01 HL140961/HL/NHLBI NIH HHS/United States ; R01 EY031939/EY/NEI NIH HHS/United States ; R01 CA167291/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Choroidal Neovascularization/pathology/metabolism/drug therapy ; Mice ; *DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism/genetics/antagonists &amp; inhibitors ; Mice, Inbred C57BL ; Mice, Knockout ; Disease Models, Animal ; Male ; Receptors, LDL ; },
abstract = {Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV). Here, we set out to further explore Ref-1 in neovascular eye disease. Ref-1 was highly expressed in human nAMD, murine laser-induced CNV and Vldlr[-/-] mouse subretinal neovascularization (SRN). Ref-1's interaction with a redox-specific small molecule inhibitor, APX2009, was shown by NMR and docking. This compound blocks crucial angiogenic features in multiple endothelial cell types. APX2009 also ameliorated murine laser-induced choroidal neovascularization (L-CNV) when delivered intravitreally. Moreover, systemic APX2009 reduced murine SRN and downregulated the expression of Ref-1 redox regulated HIF-1α target carbonic anhydrase 9 (CA9) in the Vldlr[-/-] mouse model. Our data validate the redox function of Ref-1 as a critical regulator of ocular angiogenesis, indicating that inhibition of Ref-1 holds therapeutic potential for treating nAMD.},
}
@article {pmid39755419,
year = {2025},
author = {Garg, SJ and Regillo, CD},
title = {Management of Large Submacular Hemorrhage Secondary to Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {1},
pages = {1-3},
doi = {10.1016/j.oret.2024.09.006},
pmid = {39755419},
issn = {2468-6530},
}
@article {pmid39754030,
year = {2025},
author = {Savastano, MC and Giannuzzi, F and Savastano, A and Cestrone, V and Boselli, F and Carlà, MM and D'Onofrio, NC and Biagini, I and Rizzo, C and Bianchi, M and Valentini, CG and Teofili, L and Urbani, A and Iavarone, F and Rizzo, S},
title = {Cord blood platelet-rich plasma: proteomics analysis for ophthalmic applications.},
journal = {Clinical proteomics},
volume = {22},
number = {1},
pages = {1},
pmid = {39754030},
issn = {1542-6416},
abstract = {Our objective is to determine the protein and complements constituents of Cord blood Platelet-rich plasma (CB-PRP), based on the hypothesis that it contains beneficial components capable of arresting or potentially decelerating the advancement of atrophic age-related macular degeneration (dry-AMD), with the support of radiomics. Two distinct pools of CB-PRP were assessed, each pool obtained from a total of 15 umbilical cord-blood donors. One aliquot of each pool respectively was subjected to proteomic analysis in order to enhance the significance of our findings, by identifying proteins that are shared between the two sample pools and gaining insights into the pathways they are associated with. The bioinformatics analysis was developed using Reactome software. Three-hundred-seven (307) distinct proteins were found. Two hundred fifteen (215) of the elements mentioned above are shared by both pools. Seventy (70) elements are exclusive to pool S1, while pool S2 contains 22. We detected 109 representative and statistically significant pathways out of 549. We found proteins related to the immune system, signal transduction, vesicle-mediated transport, cell-cell communication, hemostasis, cellular responses to stimuli, cell cycle, and developmental biology. The analysis showed the presence of P15692-12, representing VEGF factor A, long form. With over 200 proteins, the CB-PRP can increase the immune response, including BCR, CD-22, FCGR, phospholipids, IL-10, FCGR-3A, and others. Discovering crucial trophic and complement-regulating variables is highly significant for potential applications in dry AMD. Our future research will examine the effects of intravitreal CB-PRP on dry-AMD eyes.},
}
@article {pmid39753683,
year = {2025},
author = {Ferreira, J},
title = {Rabbit model of age-related macular degeneration.},
journal = {Lab animal},
volume = {54},
number = {1},
pages = {6},
doi = {10.1038/s41684-024-01503-2},
pmid = {39753683},
issn = {1548-4475},
}
@article {pmid39753135,
year = {2025},
author = {ten Brink, SCA and Koolen, L and Klaver, CCW and Bakker, RA and den Hollander, AI and Almedawar, S},
title = {Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants.},
journal = {Stem cell reports},
volume = {20},
number = {1},
pages = {102385},
pmid = {39753135},
issn = {2213-6711},
mesh = {*Retinal Pigment Epithelium/metabolism/pathology/cytology ; Humans ; *Complement Factor H/genetics/metabolism ; *Macular Degeneration/genetics/pathology/metabolism ; Induced Pluripotent Stem Cells/metabolism/cytology ; Phagocytosis ; Cholesterol/metabolism ; Mitochondria/metabolism ; Epithelial Cells/metabolism ; Retinal Photoreceptor Cell Outer Segment/metabolism ; Retinoids ; },
abstract = {Complement factor H (CFH) common genetic variants have been associated with age-related macular degeneration (AMD). While most previous in vitro RPE studies focused on the common p.His402Tyr CFH variant, we characterized rare CFH variants that are highly penetrant for AMD using induced pluripotent stem-cell-derived retinal pigment epithelium (iPSC-RPE). Our results show that lower factor H (FH) levels are detected in AMD RPE, which potentially disrupt canonical and non-canonical roles of FH. Specifically, AMD RPE displays higher inflammation rate and a reduced set of differentially expressed genes compared to control RPE upon N-retinylidene-N-retinylethanolamine (A2E) and blue light challenge. Additionally, cholesterol efflux and photoreceptor outer segment (POS) phagocytosis defects, dysregulated complement levels, larger sub-RPE deposits, and increased mitochondrial stress were observed in AMD RPE. Thus, our study reveals new non-canonical roles for FH in regulating important RPE functions.},
}
@article {pmid39751990,
year = {2025},
author = {Zhao, Y and Sun, M and Pan, Z and Kong, W and Hong, Z and Zhang, W and Sun, B and Zhang, J and Wang, X and Wang, K},
title = {A novel quantitative angiogenesis assay based on visualized vascular organoid.},
journal = {Angiogenesis},
volume = {28},
number = {1},
pages = {10},
pmid = {39751990},
issn = {1573-7209},
support = {8234705//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Organoids/blood supply/drug effects/metabolism ; *Neovascularization, Physiologic/drug effects ; Angiogenesis Inhibitors/pharmacology ; Pluripotent Stem Cells/metabolism/cytology/drug effects ; Cell Line ; Neovascularization, Pathologic/pathology/metabolism ; Angiogenesis ; },
abstract = {Angiogenesis describes the sprouting of blood vessels from existing vasculatures and it plays a pivotal role in disease progress such as diabetes, age-related macular degeneration and cancer. However, the most widely used anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) pathway still lacked of specificity and therapeutic efficacy. To establish a method suitable for high-throughput drug screening and faithfully recapitulate the feature of in vivo angiogenesis, we generated a PECAM1-mRuby3-secNluc; ACTA2-EGFP dual reporter human pluripotent stem cell (hPSC) line and utilizing the cell line to establish a visualized and quantifiable in vitro angiogenesis model with stem cell-derived vascular organoid. Using this method, we evaluated the anti-angiogenic effect of VEGFR inhibitor and efficiently identified several potential candidates of pro- and anti-angiogenic therapy via bioluminescence-based quantification. Overall, our study provides a valuable platform for in vitro drug screenings.},
}
@article {pmid39751765,
year = {2025},
author = {Dias, MF and Cruz-Cazarim, ELC and Pittella, F and Baião, A and Pacheco, AC and Sarmento, B and Fialho, SL},
title = {Co-delivery of antioxidants and siRNA-VEGF: promising treatment for age-related macular degeneration.},
journal = {Drug delivery and translational research},
volume = {15},
number = {7},
pages = {2272-2300},
pmid = {39751765},
issn = {2190-3948},
support = {APQ-04449-22//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais/ ; RED-00053-21//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais/ ; 2021.05027.BD//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; 2020.06611.BD//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; },
mesh = {Humans ; *Antioxidants/administration &amp; dosage/therapeutic use ; *Macular Degeneration/drug therapy/therapy/genetics ; Animals ; *RNA, Small Interfering/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/genetics ; Angiogenesis Inhibitors/administration &amp; dosage ; Drug Delivery Systems ; },
abstract = {Current treatments for retinal disorders are anti-angiogenic agents, laser photocoagulation, and photodynamic therapies. These conventional treatments focus on reducing abnormal blood vessel formation in the retina, which, in a low-oxygen environment, can lead to harmful proliferation of endothelial cells. This results in dysfunctional, leaky blood vessels that cause retinal edema, hemorrhage, and vision loss. Age-related Macular Degeneration is a primary cause of vision loss and blindness in the elderly, impacting around 20% of those over 50 years old. This complex disease is also closely related to oxidative stress in retina. In this review, we explore the challenge of treating retinal diseases, alternatives and possibilities of enhancing the effectiveness of therapies using co-delivery systems containing both antiangiogenic and antioxidant therapeutic agents. Despite recent proposals potential, the lack of extensive clinical studies on the long-term outcomes and optimal combinations of therapies means that the full risk profile and effectiveness of combined therapy are not yet completely understood. These factors must be carefully considered and managed by healthcare providers to optimize treatment outcomes and ensure patient safety.},
}
@article {pmid39749039,
year = {2024},
author = {Kunzmann, BC and Schweig, AS and Bartz-Schmidt, KU and Sobolewska, B},
title = {Real-World-Data of Treatment-Naïve and Previously Treated Patients Receiving Up to 3 Injections of Faricimab in Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {4029-4039},
pmid = {39749039},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate visual and anatomical outcome of consecutive patients who received intravitreal injections (IVI) of faricimab for the treatment of neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: A retrospective study of patients treated for nAMD with one to three IVIs of faricimab from October 2022 to January 2024. Demographic data, treatment history, best corrected visual acuity (BCVA), anatomic parameters, and adverse events (AEs) were collected.<br><br>RESULTS: After one IVI of faricimab, previously treated (n=160) eyes with a mean of 33.51 IVIs and treatment-na&#xef;ve (n=10) eyes showed a mean BCVA gain of +0.59&#xb1;0.52 letters (p=0.364) and +5.00&#xb1;6.50 letters (p=0.461), respectively, and a mean central subfield thickness (CST) reduction of -27.65&#xb1;5.33 &#xb5;m (p<0.001) and -94.10&#xb1;39.74 &#x3bc;m (p=0.042), respectively. In treatment-refractory eyes after switching from aflibercept (n=108), mean BCVA increased by +0.42&#xb1;0.66 (p=0.745) and the mean CST improved by -21.98&#xb1;6.04 (p<0.001). After three IVIs of faricimab previously treated (n=106) and treatment-na&#xef;ve (n=5) eyes showed a mean BCVA increase of +1.57&#xb1;0.88 letters (p=0.051) versus +12.50&#xb1;8.14 letters (p=0.185), and a mean CST reduction of -25.51&#xb1;5.82 &#xb5;m (p<0.001) versus -82.60&#xb1;36.20 &#xb5;m from baseline, respectively. In treatment-refractory eyes after switching from aflibercept (n=79), mean BCVA improved by +2.15&#xb1;1.08 letters (p=0.029) and mean CST decreased by -27.46&#xb1;7.04 &#xb5;m (p<0.001). Mean pigment epithelial detachment (PED) was also significantly reduced even between the first and the third faricimab injection in previously treated eyes (p=0.03). The proportion of eyes with intraretinal fluid and subretinal fluid improved significantly in all eyes and treatment-refractory eyes after switching from aflibercept. Ocular AEs were reported in three out of 170 eyes, and one patient had two stroke events during faricimab therapy.<br><br>CONCLUSION: Three IVIs of faricimab have the potential to improve visual acuity and anatomical parameters even in treatment-refractory nAMD eyes with a mean dosing interval of more than 6 weeks.},
}
@article {pmid39746595,
year = {2025},
author = {Huang, RS and Balas, M and Jhaveri, A and Popovic, MM and Kertes, PJ and Muni, RH},
title = {Comparison of Renal Adverse Events Between Intravitreal Anti-Vascular Endothelial Growth Factor Agents: A Meta-Analysis.},
journal = {American journal of ophthalmology},
volume = {271},
number = {},
pages = {466-477},
doi = {10.1016/j.ajo.2024.12.023},
pmid = {39746595},
issn = {1879-1891},
mesh = {Humans ; *Acute Kidney Injury/chemically induced/epidemiology ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Bevacizumab/adverse effects ; Diabetic Retinopathy/drug therapy ; Intravitreal Injections ; Macular Degeneration/drug therapy ; *Macular Edema/drug therapy ; Randomized Controlled Trials as Topic ; Ranibizumab/adverse effects ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins/adverse effects ; Retinal Vein Occlusion/drug therapy/complications ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: To compare the risk of renal adverse events, particularly acute kidney injury (AKI), between intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.<br><br>DESIGN: Meta-analysis.<br><br>METHODS: A systematic literature search was conducted on Ovid Medline, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published from January 2005 to February 2024 involving adult patients receiving anti-VEGF intravitreal injections for age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. The primary outcome was the comparative risk of AKI between anti-VEGF agents and sham injections. Secondary outcomes involved other renal adverse events. Subgroup analyses were conducted by specific disease indications. A random-effects model was used for meta-analysis to estimate risk ratios (RRs) and their 95% confidence intervals, with a P value of <.05 representing statistical significance. Risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB2) tool, and the certainty of evidence was evaluated through the Cochrane Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework.<br><br>RESULTS: A total of 10,031 eyes from 11 RCTs were included. No significant differences were found in the risk of acute or chronic renal conditions, obstructive uropathies, neoplasia, or infectious processes between anti-VEGF agents and sham therapy. AKI was reported in 5.4% (n = 10/185) of patients treated with bevacizumab, 1.3% (n = 6/456) with sham, 1.0% (n = 48/4724) with aflibercept, 0.8% (n = 15/1929) with faricimab, 0.5% (n = 5/1098) with brolucizumab, and 0.3% (n = 5/1639) with ranibizumab. No significant differences in AKI risk were observed between any of the anti-VEGF agents and sham (P > .05 for all comparisons). However, there was an increased risk of patient-reported symptoms with 1.25 mg bevacizumab compared to 2 mg aflibercept (RR = 3.26, 95% CI = 1.07-9.93, P = .04), driven primarily by reports of hematuria: 4.3% (bevacizumab), 0.7% (sham), 0.2% (aflibercept), 0.1% (faricimab), and 0.1% (ranibizumab).<br><br>CONCLUSIONS: US Food and Drug Administration (FDA)-approved intravitreal anti-VEGF agents do not significantly increase the risk of AKI compared to sham injections. Nevertheless, variations in patient-reported renal symptoms were observed across different anti-VEGF drugs. These variations were influenced primarily by differences in hematuria events, which may be a result of differential systemic absorption by these agents. These results underscore the importance of continuous monitoring and pharmacovigilance.},
}
@article {pmid39745845,
year = {2025},
author = {Saundankar, V and Borns, M and Broderick, K and Shah, B and Cowburn, S and McFadden, S and Suehs, B},
title = {Annual prevalence of geographic atrophy and wet age-related macular degeneration among Medicare Advantage enrollees in a US health plan.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {31},
number = {1},
pages = {88-94},
pmid = {39745845},
issn = {2376-1032},
mesh = {Humans ; United States/epidemiology ; Aged ; *Geographic Atrophy/epidemiology ; Female ; Male ; Prevalence ; Retrospective Studies ; Cross-Sectional Studies ; Aged, 80 and over ; *Medicare Part C/statistics &amp; numerical data ; Wet Macular Degeneration/epidemiology ; Macular Degeneration/epidemiology ; },
abstract = {BACKGROUND: Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) that can lead to visual impairment. Published studies estimate approximately 1 million people in the United States have GA in at least 1 eye. There is a lack of real-world evidence from the US payer perspective on the prevalence of AMD and GA among Medicare Advantage prescription drug (MAPD) plan enrollees.<br><br>OBJECTIVE: To estimate the annual prevalence of GA, wet AMD, and co-occurring GA and wet AMD among MAPD plan enrollees from 2018 through 2021.<br><br>METHODS: This retrospective, cross-sectional study estimated the prevalence of GA and AMD based on Medicare Advantage enrollee claims data. Individuals aged 65 years and older who had continuous enrollment throughout each calendar year constituted the denominator for each annual prevalence calculation. Enrollees with at least 1 medical claim with a diagnosis code for GA or wet AMD during each year were identified to estimate annual prevalence for that respective calendar year.<br><br>RESULTS: The total number of patients in the denominator was 2,175,803 (2018); 2,445,163 (2019); 2,680,322 (2020); and 2,905,366 (2021). The annual prevalence of GA was 0.56% (2018), 0.55% (2019), 0.48% (2020), and 0.51% (2021). The annual prevalence of wet AMD was 1.2% (2018), 1.3% (2019), 1.2% (2020), and 1.3% (2021). The prevalence of GA was highest among individuals classified as White race (annual range 0.61% to 0.71%) and among patients with GA aged 75 years and older (range 0.95% to 1.11%). The proportion of patients with GA with co-occurring wet AMD was 25.6% to 28.0%. The annual prevalence of advanced AMD (GA or wet AMD) was 1.6% to 1.7%.<br><br>CONCLUSIONS: In the Medicare populations, the prevalence of GA was greatest among patients aged 75 years and older and individuals classified as White race. A substantial proportion of individuals with GA had evidence of co-occurring wet AMD. MAPD plans should evaluate how their membership may be impacted by the recently approved medications for the treatment of GA.},
}
@article {pmid39745839,
year = {2025},
author = {Saundankar, V and Borns, M and Broderick, K and Shah, B and Cowburn, S and McFadden, S and Suehs, B},
title = {Geographic atrophy and factors associated with disease progression among Medicare Advantage enrollees.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {31},
number = {1},
pages = {42-52},
pmid = {39745839},
issn = {2376-1032},
mesh = {Humans ; United States/epidemiology ; *Disease Progression ; *Medicare Part C/statistics &amp; numerical data ; Male ; Female ; Retrospective Studies ; *Geographic Atrophy/epidemiology ; Aged ; Aged, 80 and over ; Blindness/epidemiology/etiology ; },
abstract = {BACKGROUND: Geographic atrophy (GA) is a form of advanced age-related macular degeneration (AMD) that can cause irreversible vision impairment and is responsible for approximately 20% of legal blindness in the United States. There is limited real-world evidence assessing health outcomes and health care resource use (HCRU) among individuals with GA.<br><br>OBJECTIVE: To examine the progression from GA without subfoveal involvement (SFI) to GA with SFI, progression to irreversible blindness, and HCRU among older individuals with GA enrolled in Medicare Advantage Prescription Drug (MAPD) plans.<br><br>METHODS: This retrospective study used claims data for MAPD-plan enrollees aged at least 65 years with an AMD diagnosis between 2018 and 2021. To assess progression of GA, development of blindness, and HCRU, propensity score matched cohorts of individuals with GA and without GA were identified and compared. For GA progression analysis, at least 12 months of follow-up was required, and patients were followed until the end of either follow-up or study period.<br><br>RESULTS: Total 9,511 individuals with GA were matched 1:1 to individuals without GA. Among individuals with GA, initial diagnosis was primarily by an ophthalmologist (58.6%) followed by an optometrist (30.9%). The most common diagnostic imaging procedure at index was optical coherence tomography (53.0%). Mean follow-up time was 2.3 years. At index, 4,781 (50.3%) individuals had GA without SFI and 4,697 (49.4%) had GA with SFI. Among individuals with GA without SFI at index, 479 (10.2%) progressed to GA with SFI during the 12-month follow-up. Among individuals with GA without SFI at index, 173 (3.6%) developed irreversible blindness, compared to 312 (6.6%) of those with SFI, and 51 (0.5%) individuals without GA. Kaplan-Meier analysis indicated fastest progression to irreversible blindness among individuals with GA with SFI, followed by those without SFI (log-rank test P < 0.001). Both diagnosis of GA without SFI (hazard ratio [HR] [CI] = 6.77 [4.98-9.35], P < 0.001) and diagnosis of GA with SFI (HR [CI] = 12.59 [9.43-17.16], P < 0.001) were strongly associated with increased risk of developing irreversible blindness. Significant predictors of progression to GA with SFI were wet AMD at baseline (HR [CI] = 5.70 [4.63-6.99], P < 0.001), Elixhauser comorbidity score of 4-5 (HR [CI] = 1.46 [1.12-1.91], P = 0.006), and more than 5 (HR [CI] = 1.40 [1.02-1.89], P = 0.035).<br><br>CONCLUSIONS: GA with or without SFI was associated with progression to irreversible blindness in an MAPD-plan population. Patients with GA with SFI progressed to irreversible blindness faster than patients with GA without SFI. With the recent approval of GA treatments, future research is needed to assess the impacts on disease progression, including blindness.},
}
@article {pmid39744871,
year = {2025},
author = {Zhang, M and Wu, J and Wang, Y and Wu, Y and Wan, X and Jiang, M and Bo, Q and Chen, J and Sun, X},
title = {circSIRT2/miR-542-3p/VASH1 axis regulates endothelial-to-mesenchymal transition (EndMT) in subretinal fibrosis in age-related macular degeneration models.},
journal = {Aging cell},
volume = {24},
number = {4},
pages = {e14443},
pmid = {39744871},
issn = {1474-9726},
support = {82101159//National Natural Science Foundation of China/ ; 82171076//National Natural Science Foundation of China/ ; 82301220//National Natural Science Foundation of China/ ; 82301221//National Natural Science Foundation of China/ ; 22YF1435500//Shanghai Sailing Program/ ; 23YF1434100//Shanghai Sailing Program/ ; },
mesh = {Humans ; *MicroRNAs/metabolism/genetics ; Animals ; *RNA, Circular/genetics/metabolism ; Mice ; Fibrosis ; Disease Models, Animal ; *Macular Degeneration/genetics/pathology/metabolism ; *Epithelial-Mesenchymal Transition/genetics ; Human Umbilical Vein Endothelial Cells ; *Cell Cycle Proteins/metabolism/genetics ; *Retina/pathology/metabolism ; Choroidal Neovascularization ; Endothelial-Mesenchymal Transition ; },
abstract = {Neovascular age-related macular degeneration (nAMD), characterized by choroidal neovascularization (CNV), is one of the leading causes of severe visual impairment and irreversible vision loss around the world. Subretinal fibrosis (SRF) contributes to the incomplete response to anti-vascular endothelial growth factor (VEGF) treatment and is one of the main reasons for long-term poor visual outcomes in nAMD. Reducing SRF is urgently needed in the anti-VEGF era. The role of non-coding RNAs has been implicated in CNV; however, their roles in SRF have not been elucidated yet. Herein, we comprehensively investigated circular RNA (circRNA) profiles in the laser-induced mouse SRF model and the transforming growth factor-β (TGF-β) induced human umbilical vein endothelial cell (HUVEC) fibrosis model. A novel circRNA, circSIRT2, was identified, and its function in SRF and endothelial-to-mesenchymal transition (EndMT) regulation was investigated. circSIRT2 was consistently upregulated in fibrotic models in vivo and in vitro. circSIRT2 overexpression downregulated the fibrotic markers and inhibited the proliferation and migration of endothelial cells in vitro. circSIRT2 overexpression in vivo also reduced SRF area in mice. Mechanistically, circSIRT2 functioned by sponging miR-542-3p, which further upregulated the expression of vasohibin-1 (VASH1) and reduced SRF lesion development. Vitreous delivery of miR-542-3p and VASH1 in the mouse SRF model also confirmed the pro-fibrotic function of miR-542-3p and anti-fibrotic function of VASH1, respectively. In conclusion, circSIRT2 inhibited SRF by binding miR-542-3p, which stimulated the VASH1 expression and subsequently suppressed EndMT. The circSIRT2/miR-542-3p/VASH1 axis may serve as a promising therapeutic target for SRF in nAMD.},
}
@article {pmid39742645,
year = {2025},
author = {Françon, A and Jonet, L and Behar-Cohen, F and Torriglia, A},
title = {Repeated exposure to low doses of light induces retinal damage in vivo in a wavelength-dependent manner.},
journal = {Ecotoxicology and environmental safety},
volume = {290},
number = {},
pages = {117605},
doi = {10.1016/j.ecoenv.2024.117605},
pmid = {39742645},
issn = {1090-2414},
mesh = {Animals ; *Light/adverse effects ; *Retina/radiation effects/pathology ; Rats ; Male ; Rats, Wistar ; },
abstract = {The exposure of the general population to artificial light at night has dramatically increased in recent decades. Current standards for domestic lighting are based on acute exposure to light and consider blue wavelengths to be responsible for phototoxicity. However, meta-analyses pointed out the role of lifelong light exposure in the onset of age-related macular degeneration, suggesting a cumulative effect of light exposure. Here, we investigate the retinal phototoxicity of a repeated exposure to light emitting diodes of different spectral compositions in 6-week-old albino rats. Rats were exposed twice a day for 15 days to retinal doses that were safe in acute exposure (0.1 and 0.2 J/cm[2] for blue and white lights, 0.2 J/cm[2] for green light and 0.05 J/cm[2] for red light). We show that rats repeatedly exposed to blue and white lights display irreversible retinal damage, characterized by a degradation of the global retinal structure, a significant photoreceptor loss, and an increase of stress and inflammation markers. We highlight the role of green wavelengths in the phototoxicity of white light and show the protective effect of the addition of red light to mitigate the phototoxicity of blue light. All of this points out the need to rethink the current phototoxicity standards by taking into account the cumulative effect of the exposure to light and the role of the different parts of the emission spectrum.},
}
@article {pmid39742409,
year = {2024},
author = {Khalatyan, AS and Yusef, Y and Avetisov, KS and Plyukhova, AA},
title = {[Cognitive impairment and age-related eye pathology.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {37},
number = {5},
pages = {559-565},
pmid = {39742409},
issn = {1561-9125},
mesh = {Humans ; *Macular Degeneration/physiopathology/etiology/metabolism ; *Cognitive Dysfunction/etiology/metabolism/physiopathology ; *Alzheimer Disease/metabolism/pathology/physiopathology/etiology ; Glaucoma/physiopathology/metabolism/complications/etiology ; Aging/physiology/metabolism/pathology ; Aged ; },
abstract = {In developed countries age-related macular degeneration (AMD) and glaucoma are the most common diseases of old age that cause irreversible blindness. Alzheimer's disease (AD), the most prevalent cause of dementia among older adults, is often associated with AMD and glaucoma. Features of AD include extracellular accumulation of β-amyloid (Aβ) and intracellular deposits of hyperphosphorylated forms of tau-protein. In addition, neuroinflammation and impaired iron metabolism in the brain are involved in the pathogenesis of AD, which ultimately leads to progressive neuronal death and dementia. It was found that the retina of patients with AMD also accumulates Aβ and iron, as well as Aβ and p-tau in retinal ganglion cells affected by glaucoma, and concomitant inflammation aggravates the pathological process. Patients with AD experience a marked decline in visual function which is thought to develop before the decline in cognitive function. Some are caused by degeneration of the visual cortex, others by retinal ganglion cell loss or retinal degeneration associated with AMD.},
}
@article {pmid39742182,
year = {2024},
author = {Pantelidou, ME and Sunnucks, D and Pantelidis, EP},
title = {Maculopathies: A Systematic Literature Review on Pathophysiology, Public Health, and Treatment.},
journal = {Cureus},
volume = {16},
number = {12},
pages = {e74911},
pmid = {39742182},
issn = {2168-8184},
abstract = {Macular degeneration (MD) is a pathological condition affecting the macula, an area located near the center of the retina. This disease affects individuals of all ages, both children and adults, causing severe visual impairment. Age-related macular degeneration (AMD) is the leading cause of visual loss in the older population while Stargardt disease (SD) is the most common hereditary maculopathy with an autosomal dominant pattern of inheritance. Current management involves anti-vascular endothelial growth factor intravitreal injections, visual aids, and other conservative prevention mechanisms that can only delay the inevitable progress of the disease. Macular dystrophies have an impact on both individuals and societies with psychological and financial implications, respectively. It is evident that vision impairment has a significant impact on patients' physical and mental well-being, and therefore it is important to improve current treatment modalities, develop stem cell therapies, and further novel treatments in order to provide a better prognosis and overall quality of life.},
}
@article {pmid39742141,
year = {2024},
author = {Szigiato, A and Maatouk, CM and Azar, AE and Alsaloum, P and Talcott, KE and Singh, RP and Rachitskaya, AV},
title = {Detection of Geographic Atrophy Guided by Optical Coherence Tomography Sub-RPE Illumination Analysis in Patients With Intermediate Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264241305107},
pmid = {39742141},
issn = {2474-1272},
abstract = {Purpose: To evaluate the prevalence of geographic atrophy (GA) lesions in patients with a diagnosis of intermediate age-related macular degeneration (iAMD). Methods: A retrospective cross-sectional study was performed of patients with an International Classification of Diseases, 10th Revision, diagnosis of iAMD. The primary outcome was the percentage of eyes diagnosed with iAMD with an undocumented GA lesion identified on imaging. Multiple logistic regression was used to assess risk factors for atrophic lesions in patients with iAMD. Results: The study included 690 eyes of 428 patients with a diagnosis of iAMD. The mean age was 79.4 ± 8.4 years, and 66.3% of patients were women. Forty-nine eyes (7.1%) were graded as having GA lesions, and 34% of these eyes had foveal involvement. The mean visual acuity (VA) was better in patients without GA lesions than in patients with GA lesions (72.9 ± 12.9 letters vs 66.4 ± 13.8 letters; P = .001). No systemic comorbidity was associated with an increased risk of GA lesions in this cohort. Conclusions: A notable proportion of eyes diagnosed with iAMD by eye care providers had underlying GA lesions in this real-world cohort. The use of optical coherence tomography as an adjunctive tool helped increase the detection of early GA in these patients.},
}
@article {pmid39741792,
year = {2024},
author = {Rush, RB and Klein, W and Rush, SW and Reinauer, RM},
title = {Real-World Outcomes in Pre-Existing Neovascular Age-Related Macular Degeneration Subjects Undergoing Avacincaptad Therapy for Geographic Atrophy.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {4011-4018},
pmid = {39741792},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate real-world outcomes in subjects with pre-existing neovascular age-related macular degeneration (AMD) undergoing intravitreal avacincaptad pegol (IVA) treatment for geographic atrophy (GA).<br><br>METHODS: This study was undertaken as a retrospective, case-controlled assessment of patients undergoing IVA treatment for GA from 2 community-based retina practices. Patients were separated into 1) a Study Group consisting of subjects with pre-existing neovascular AMD prior to initiation of IVA for GA, and 2) a Control Group consisting of AMD subjects without neovascularization prior to initiation of IVA for GA. Study and Control Group subjects had a baseline visual acuity of &#x2265; 20/200, a total GA lesion area of &#x2265; 1 mm[2] and &#x2264; 17.5 mm[2], and follow-up of 12-months following IVA commencement.<br><br>RESULTS: A total of 64 patients were analyzed. No significant differences in baseline characteristics were found between cohorts. The Study Group had a greater decrease in visual acuity [-0.2 (-0.24 to -0.16) logMAR versus -0.04 (-0.06 to 0.02) logMAR; p<0.0001], a greater increase in GA lesion growth [1.36 (1.09-1.63) mm[2] versus 0.52 (0.34-0.70) mm[2]; p<0.0001], and a higher incidence of exudation (p=0.0002) compared to the Control Group during the study period.<br><br>CONCLUSION: This study suggests that patients undergoing IVA therapy for GA with pre-existing neovascular AMD have worse visual and anatomic outcomes at 12-months compared to a matched control group without pre-existing neovascularization; such patients therefore should be carefully counseled prior to initiation of IVA for the management of GA.},
}
@article {pmid39741521,
year = {2024},
author = {Chakravarthy, H and Georgyev, V and Wagen, C and Hosseini, A and Matsubara, J},
title = {Blue light-induced phototoxicity in retinal cells: implications in age-related macular degeneration.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1509434},
pmid = {39741521},
issn = {1663-4365},
abstract = {Sunlight exposure is recognized as a risk factor for the development of age-related macular degeneration (AMD), a common neurodegenerative retinal disease in the elderly. Specifically, the blue light wavelengths within sunlight can negatively impact the physiology of light-sensitive retinal cells, including retinal pigmented epithelium (RPE) and photoreceptors. This review explores blue light-induced retinal degeneration, emphasizing the structural and functional impairments in RPE. The initial section provides a brief overview of blue light's effects on photoreceptors, followed by a comprehensive analysis of its detrimental impact on RPE. In vitro studies reveal that blue light exposure induces morphological alterations and functional impairments in RPE, including reduced phagocytic activity, disrupted secretion of neurotrophic factors, and compromised barrier function. Mechanisms of retinal damage, including oxidative stress, inflammation, lipofuscin accumulation, mitochondrial dysfunction and ER stress in RPE, are also explored. The strengths and limitations of in vitro, animal and ex vivo models for studying blue light exposure are discussed, with recommendations for improving reproducibility in future studies.},
}
@article {pmid39739349,
year = {2024},
author = {Yu, J and Zhang, Y and Ho, M and Zhang, XJ and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association of Metabolomics With Incidence of Age-Related Macular Degeneration: The UK Biobank Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {43},
pmid = {39739349},
issn = {1552-5783},
mesh = {Humans ; Incidence ; *Macular Degeneration/epidemiology/blood ; Female ; Male ; Prospective Studies ; *Metabolomics/methods ; United Kingdom/epidemiology ; Aged ; Middle Aged ; Risk Factors ; Biological Specimen Banks ; Follow-Up Studies ; ROC Curve ; Biomarkers/blood ; Proportional Hazards Models ; UK Biobank ; },
abstract = {PURPOSE: The purpose of this study was to identify serum metabolites associated with age-related macular degeneration (AMD) incidence and investigate whether metabolite profiles enhance AMD risk prediction.<br><br>METHODS: In a prospective cohort study involving 240,317 UK Biobank participants, we assessed the associations of 168 metabolites with AMD incidence using Cox hazards models. Principal component analysis (PCA) captured 90% of the variance in metabolites. These principal components (PCs) were added to the Cox models, with the first PC selected to evaluate model performance using receiver operating characteristic (ROC) curves.<br><br>RESULTS: During a median follow-up of 13.69 years, 5199 (2.16%) participants developed AMD. After accounting for demographic, lifestyle, multimorbidity, socioeconomic factors, and genetic predispositions to AMD, 42 metabolites were associated with AMD incidence. Very-low-density lipoprotein (VLDL)-related particles, low-density lipoprotein (LDL)-related particles, three additional lipids particles, and albumin were associated with decreased AMD incidence, whereas glucose increased the risk of AMD incidence. Compared to those in the lowest quartile, individuals in the highest quartile of protective metabolite scores exhibited lower risk of AMD incidence (hazard ratio [HR] = 0.869, 95% confidence interval [CI] = 0.803-0.940, false discovery rate [FDR]-adjusted P = 1.44 &#xd7; 10-3). However, the AMD-associated metabolites did not enhance predictive performance (both areas under the curve [AUC] = 0.776).<br><br>CONCLUSIONS: Our findings reveal significant associations between specific metabolites and AMD incidence, highlighting the roles of lipoprotein subclasses, cholesterol subtypes, apolipoproteins, glucose, and albumin. Although metabolomics did not improve risk prediction, certain biomarkers may serve as promising therapeutic targets.},
}
@article {pmid39739348,
year = {2024},
author = {Viggiano, P and Boscia, G and Giannaccare, G and Santoro, M and Petrara, G and Borriello, C and Borrelli, E and Reibaldi, M and Grassi, MO and Alessio, G and Boscia, F},
title = {Topographical Quantification of Hyper-Reflective Foci May Predict the Development of Macular Atrophy in Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {45},
pmid = {39739348},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis/complications ; *Intravitreal Injections ; Aged, 80 and over ; Visual Acuity ; Fluorescein Angiography/methods ; Atrophy ; Macula Lutea/pathology/diagnostic imaging ; Follow-Up Studies ; Ranibizumab/therapeutic use ; Middle Aged ; },
abstract = {PURPOSE: The purpose of this study was o examine the optical coherence tomographic (OCT) characteristics of hyper-reflective foci (HRF) in patients with neovascular age-related macular degeneration (nAMD) and to assess the potential of HRF as a predictive factor for the development of macular atrophy following anti-vascular endothelial growth factor (anti-VEGF) therapy.<br><br>METHODS: This was a retrospective analysis of 61 treatment-na&#xef;ve eyes diagnosed with exudative AMD and type 1 macular neovascularization (MNV). The HRF was identified in the inner retina and outer retina layers, and the treatment response of HRF was documented. An analysis was conducted to explore the association between HRF and the development of macular atrophy.<br><br>RESULTS: The number of HRF in the inner retina and outer retina layers showed significant reduction after 12&#xa0;months of anti-VEGF treatment (P = 0.002 and P < 0.0001, respectively). Similarly, compared with baseline, the number of HRFs in the inner retina and outer retina layers was significantly reduced after 24&#xa0;months of anti-VEGF treatment (P = 0.002 and P < 0.0001, respectively). Moreover, the multivariate linear regression analysis revealed that the most substantial associations observed with the development of macular atrophy after 12&#xa0;months were specifically tied to the number of HRFs in the outer retina (P = 0.039) at the baseline visit. This finding was confirmed after 24&#xa0;months of anti-VEGF treatment (P = 0.007).<br><br>CONCLUSIONS: After only 1 year of antiangiogenic therapy, there was a significant decrease in HRFs observed across all retinal layers. This reduction persisted even after 2 years of anti-VEGF treatment. Notably, the quantity of HRFs in the outer retina at baseline exhibited a correlation with the development of macular atrophy that endured at both the 1-year and 2-year follow-ups after anti-VEGF treatment.},
}
@article {pmid39738534,
year = {2024},
author = {Nonogaki, R and Ota, H and Takeuchi, J and Nakano, Y and Sajiki, AF and Todoroki, T and Nakamura, K and Kaneko, H and Nishiguchi, KM},
title = {Analysis of the aqueous humor before and after the administration of faricimab in patients with nAMD.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {31951},
pmid = {39738534},
issn = {2045-2322},
mesh = {Humans ; *Aqueous Humor/metabolism/drug effects ; Male ; Female ; Aged ; *Angiopoietin-2/metabolism ; *Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; Aged, 80 and over ; Intravitreal Injections ; Visual Acuity/drug effects ; Placenta Growth Factor/metabolism ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Biomarkers ; Middle Aged ; },
abstract = {This study aimed to evaluate the changes in cytokine levels in the aqueous humor and factors of treatment resistance following intravitreal faricimab injection in treatment-naïve patients with neovascular age-related macular degeneration. A total of 32 eyes were analyzed before and after a single faricimab injection. Although the best-corrected visual acuity (BCVA) showed no significant improvement, the mean central retinal thickness decreased significantly by 73.7% (P < 0.01), and more than 90% of the eyes showed improvement in exudative changes 1 month after faricimab injection. Moreover, the aqueous humor concentrations of vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang)-2, and placental growth factor considerably decreased 1 month after faricimab injection. Multivariate analyses adjusted for age, sex, BCVA, central choroidal thickness, and aqueous humor cytokines revealed that higher Ang-2 levels in the aqueous humor at baseline were associated with better treatment response to faricimab injection. These findings suggest that the dual inhibition of VEGF-A and Ang-2 by faricimab is effective in reducing exudative changes and that Ang-2 may serve as a potential biomarker for predicting faricimab treatment response.},
}
@article {pmid39738409,
year = {2024},
author = {Sumer, F and Subasi, S and Bahceci, I and Satilmaz, MF},
title = {Evaluation of serum galectin-3 concentration as a potential biomarker in exudative-type age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {31957},
pmid = {39738409},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; *Biomarkers/blood ; Aged ; Case-Control Studies ; *Galectin 3/blood ; *Macular Degeneration/blood/diagnosis ; Middle Aged ; Prospective Studies ; Galectins/blood ; C-Reactive Protein/metabolism/analysis ; Blood Proteins/analysis ; },
abstract = {To investigate the effect of serum galectin-3 on naive neovascular AMD and its use as a serum marker by revealing the variation in this molecule between patient and control groups. Fifty-six naive neovascular AMD patients and 30 healthy control age-matched healthy subjects were included in this prospective case‒control study. Blood samples were obtained and used for analysis of complete blood count; High sensitivity C-reactive protein (HsCRP), erythrocyte sedimentation rate (ESR), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), total cholesterol, homocysteine, HbA1c and galectin-3 levels. The average HsCRP level in the AMD group was significantly higher than that in the control group (p < 0.001). The median leukocyte count was significantly higher in the AMD group than in the control group (p < 0.001). Total cholesterol, LDL and TG levels were significantly higher in the AMD group than in the control group (p < 0.001; in all comparisons). The mean HDL level was significantly lower in the AMD group than in the control group (p < 0.001). The mean galectin-3 level was 8.79 ± 0.55 in the AMD group and 6.55 ± 0.55 in the control group. There was a statistically significant increase in galectin-3 levels in the AMD group (p < 0.001). There was a significant positive correlation between CMT and galectin-3 levels in the control (r = 0.495, p = 0.005) and AMD (r = 0.776, p < 0.001) groups. This study reports that serum Gal-3 concentration was higher in the AMD group compared to the control group and positively correlated with CMT.},
}
@article {pmid39737263,
year = {2024},
author = {Bidiwala, S},
title = {Efficacy of Anti-Vascular Endothelial Growth Factor (VEGF) Therapy for Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {16},
number = {11},
pages = {e74776},
pmid = {39737263},
issn = {2168-8184},
abstract = {Anti-vascular endothelial growth factor (VEGF) drugs are used for various diseases with abnormal proliferation of blood vessels. The use of these drugs in wet age-related macular degeneration (AMD) has proven to be highly effective. Various factors contribute to the efficacy of these drugs in different settings. Many studies have proven that these drugs effectively slow disease progress and improve visual outcomes. Factors contributing to the success or failure of the treatment include the genetic makeup of the patient, comorbidities, compliance with the clinic visits and injections, long-term follow-up for the treatment, socioeconomic status, and availability of different drugs. The treatment of choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) has been revolutionized after the introduction of anti-VEGF therapy. However, there are still some gaps in the literature that require the attention of the researchers. Our literature review has evaluated anti-VEGF use over the years and analyzed the efficiency of drugs in different settings. It showed that all the anti-VEGF drugs depict similar visual results for one to two years. The long-term evaluation of any drug cannot be commented on yet and needs further evidence through different research. These drugs improve visual function and the anatomical results of patients with other eye problems. These drugs' adverse effects are rare but still an important point requiring further research. Clinical outcomes of the drugs must be ascertained through patients' eyes to assess the quality of life improvement appropriately. The cost-effectiveness of the drugs is a substantial debatable topic, as bevacizumab is cost-effective but still requires Food and Drug Administration (FDA) approval.},
}
@article {pmid39736411,
year = {2025},
author = {Zhang, A and Wei, TT and Tan, X and Tan, CY and Zhuang, M and Xie, TH and Cai, J and Yao, Y and Zhu, L},
title = {FADS1 inhibition protects retinal pigment epithelium cells from ferroptosis in age related macular degeneration.},
journal = {European journal of pharmacology},
volume = {989},
number = {},
pages = {177227},
doi = {10.1016/j.ejphar.2024.177227},
pmid = {39736411},
issn = {1879-0712},
mesh = {*Ferroptosis/drug effects ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism/cytology ; *Macular Degeneration/pathology/metabolism/drug therapy ; Animals ; Humans ; *Fatty Acid Desaturases/antagonists &amp; inhibitors/genetics/metabolism ; Mice ; Delta-5 Fatty Acid Desaturase ; Cell Line ; Mice, Inbred C57BL ; Lipid Peroxidation/drug effects ; Male ; Disease Models, Animal ; Sp1 Transcription Factor/metabolism/antagonists &amp; inhibitors ; *Enzyme Inhibitors/pharmacology ; Reactive Oxygen Species/metabolism ; Female ; Aged ; Cell Survival/drug effects ; Iodates ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly individuals. Retinal pigment epithelium (RPE) ferroptosis is a significant pathogenetic component in AMD. This study aims to elucidate the role and mechanisms of fatty acid desaturase 1 (FADS1) in ferroptosis as well as AMD progression.<br><br>METHODS: An integrated bioinformatics analysis based on the array of data from the GEO database was conducted to identify candidates involved in ferroptosis during AMD. Subsequently, cellular and mouse models of AMD were developed using sodium iodate (NaIO3) to confirm the altered expression of FADS1. After treatment with a FADS1 inhibitor, cell survival, lipid peroxidation, and indicators of AMD were assessed in vitro and in vivo models. Further, immunofluorescence, immunohistochemistry, and swept-source OCT imaging were performed to assess the impacts of pharmacological inhibition of transcription factor specificity protein 1 (Sp1) on FADS1 and ferroptosis.<br><br>RESULTS: FADS1 expression was upregulated in AMD patients and in vitro and in vivo models of AMD. Its pharmacological inhibition had decreased mitochondrial ROS formation, lipid peroxidation, and ferroptosis as well as increased RPE cell function in ARPE-19&#xa0;cells and C57BL/6J mouse models of AMD. Mechanistically, Sp1 was identified as a key transcription factor of FADS1. Moreover, Sp1 inhibition downregulated FADS1 expression consequently attenuating FADS1-mediated ferroptosis as well as AMD phenotypes.<br><br>CONCLUSION: For the first time, we demonstrated that Sp1 regulates FADS1-mediated ferroptosis in RPE cells. Our findings provide novel insights into the progression and treatment of AMD.},
}
@article {pmid39735855,
year = {2024},
author = {Deng, L and Wang, L and Meng, Y and Zheng, J and Dong, X and Chen, Y and Huang, H},
title = {A Novel Bispecific Anti-IL17/VEGF Fusion Trap Exhibits Potent and Long-Lasting Inhibitory Effects on the Development of Age-Related Macular Degeneration.},
journal = {Biochemistry research international},
volume = {2024},
number = {},
pages = {1405338},
pmid = {39735855},
issn = {2090-2247},
abstract = {Age-related macular degeneration (AMD) is a severe eye disease in people aged 60 years and older. Although anti-VEGF therapies are effective in treating neovascular AMD (NvAMD) in the clinic, up to 60% of patients do not completely respond to the therapies. Recent studies have shown that blood-derived macrophages and their associated proinflammatory cytokines may play important roles in the development of persistent disease and resistance to anti-VEGF therapy. To address this issue, we constructed an antibody-based bispecific fusion protein that can simultaneously inhibit IL-17-induced inflammation and VEGF-mediated neovascularization. As a result, the bispecific fusion protein 17V05 effectively inhibited multiple proinflammatory cytokines and chemokines, as well as laser-induced choroidal neovascularization (CNV). More importantly, 17V05 also exhibited stronger and longer inhibitory effects than conbercept in vivo. Thus, we provide a novel and promising strategy for treating AMD patients who are not sensitive to anti-VEGF therapies.},
}
@article {pmid39734575,
year = {2024},
author = {Liu, X and Cao, Y and Wang, Y and Kang, L and Zhang, G and Zhang, J and Qin, B and Yang, L and Luo, J and Li, P and Geng, W and Ji, M and Guan, H},
title = {Systemic inflammatory regulators and age-related macular degeneration: a bidirectional Mendelian randomization study.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1391999},
pmid = {39734575},
issn = {1664-8021},
abstract = {INTRODUCTION: We investigated the relationship between systematic regulators of inflammation and the risk of age-related macular degeneration (AMD), both wet and dry forms, by using bidirectional, two-sample Mendelian randomization (MR).<br><br>METHODS: We performed bidirectional two-sample Mendelian randomization analysis using genome-wide study (GWAS) data for 91 plasma proteins from 14,824 individuals of European descent across 11 study groups. Next, we utilized data from the FinnGen consortium to study AMD using the inverse- variance-weighted approach for Mendelian randomization. Additional analyses involved MR-Egger, Weighted median, Weighted mode, MR-PRESSO, and MR- Steiger filtering techniques.<br><br>RESULTS: We identified 16 cytokines associated AMD outcomes and post FDR correction, higher levels of fibroblast growth factor 19 and leukemia inhibitory factor receptor were associated with decreased risk for AMD, while higher levels of tumour necrosis factor ligand superfamily member 14 were associated with increased risk for AMD. Additionally, higher levels of interleukin-10 receptor subunit alpha were associated with decreased risk for wet AMD, higher levels of leukemia inhibitory factor receptor were associated with decreased risk for dry AMD, and higher levels of signaling lymphocytic activation molecule were associated with increased risk for dry AMD. Genetic susceptibility to AMD was associated with elevated levels of TNF-related activation-induced cytokines (TNFSF11), and genetic susceptibility to wet AMD was associated with elevated levels of TNFSF11, interleukin-18 receptor 1 (IL18R1), and CUB domain-containing protein 1 (CDCP1).<br><br>DISCUSSION: This research enhances our understanding of systemic inflammation in AMD, providing insights into etiology, diagnosis, and treatment of AMD and its forms.},
}
@article {pmid39733838,
year = {2025},
author = {Zarbin, MA and Weng, CY and London, NJS and Koh, AHC and Gallego-Pinazo, R and Chaudhary, V and Souverain, A and Stoilov, I and Margaron, P},
title = {Disease Activity Criteria Impact Dosing Interval Assignment in Neovascular Age-related Macular Degeneration Trials.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {4},
pages = {404-407},
doi = {10.1016/j.oret.2024.12.021},
pmid = {39733838},
issn = {2468-6530},
}
@article {pmid39732424,
year = {2025},
author = {Zhang, Y and Qi, S and Shen, W and Guo, Y and Liang, Y and Zhuo, Q and Kong, H and Zhang, S and Zhao, C},
title = {Metabolomic and transcriptomic analysis reveals metabolic-immune interactions in choroid neovascularization.},
journal = {Experimental eye research},
volume = {251},
number = {},
pages = {110227},
doi = {10.1016/j.exer.2024.110227},
pmid = {39732424},
issn = {1096-0007},
mesh = {*Choroidal Neovascularization/metabolism/genetics/immunology ; Animals ; *Metabolomics/methods ; Disease Models, Animal ; Gene Expression Profiling ; *Transcriptome ; Humans ; Mice ; Macrophages/immunology ; *Choroid/metabolism ; },
abstract = {Choroid neovascularization (CNV) is a distinct type of age-related macular degeneration (AMD) with a poor prognosis and responsible for the majority of vision loss in the elderly population. The laser-induced CNV model is a well-established animal model frequently used to study CNV. In this study, we performed an integrated analysis of metabolomic and transcriptomic data from CNV samples, utilizing multiple approaches including single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and weighted gene co-expression network analysis (WGCNA), alongside various bioinformatics platforms, to identify key metabolic and immune signatures and to investigate their interplay during angiogenesis. Dominant infiltration of macrophages and monocytes was detected and a positive correlation between dysregulated riboflavin metabolism and angiogenesis pathways was characterized. Hub genes such as ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) and acid phosphatase 5, tartrate resistant (ACP5) emerged as potential central regulators of immune-metabolic crosstalk in CNV. The classification of the immune and metabolic landscape and their critical interactions in CNV models will enhance the understanding of the pathogenesis of neovascular AMD and other neovascular eye diseases, contributing to the development of multi-targeted therapeutic strategies with better efficacy.},
}
@article {pmid39731250,
year = {2024},
author = {Vlasova, AS and Petrov, SA and Renzyak, EV},
title = {[Neuroprotective therapy for age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {6},
pages = {152-158},
doi = {10.17116/oftalma2024140061152},
pmid = {39731250},
issn = {0042-465X},
mesh = {Humans ; *Macular Degeneration/therapy/physiopathology/etiology ; *Neuroprotective Agents/administration &amp; dosage ; },
abstract = {Age-related macular degeneration (AMD) is a chronic multifactorial degenerative eye disease and one of the leading causes of irreversible blindness worldwide. Despite extensive research, there is no consensus on the predominant pathological mechanism leading to photoreceptor death. AMD is associated with molecular and cellular disruptions that ultimately result in photoreceptor degeneration. This review summarizes data from international and Russian studies on the pathophysiological mechanisms underlying the development and progression of photoreceptor degeneration, presents scientific developments in therapeutic correction of these disturbances, and highlights promising avenues for pharmacological retinal neuroprotection that require further validation in clinical studies.},
}
@article {pmid39731242,
year = {2024},
author = {Zolotarev, AV and Karlova, EV and Balandina, EV and Zubkova, EY and Grishina, EE and Zamytskiy, EA and Balalayeva, NV},
title = {[Dual inhibition of VEGF-A and angiopoietin-2 in the treatment of neovascular age-related macular degeneration and diabetic macular edema].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {6},
pages = {100-106},
doi = {10.17116/oftalma2024140061100},
pmid = {39731242},
issn = {0042-465X},
mesh = {Humans ; *Macular Edema/drug therapy/etiology/diagnosis ; Male ; *Diabetic Retinopathy/drug therapy/diagnosis ; *Angiopoietin-2/antagonists &amp; inhibitors ; Female ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Visual Acuity ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; Macular Degeneration/drug therapy/diagnosis/complications ; Middle Aged ; },
abstract = {The introduction of faricimab, a drug targeting both vascular endothelial growth factor-A (VEGF-A) and angiopoietin-2, has enabled the implementation of the highly effective dual inhibition strategy in real clinical practice for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), both previously treated with intravitreal injections and newly diagnosed. This article presents a series of 11 clinical cases involving patients with nAMD and DME who received loading doses of faricimab and continued ophthalmological observation. Among them, three patients with nAMD and two with DME were treatment-naïve, while the others were switched from alternative therapies to faricimab. The duration of follow-up after the loading phase ranged from 4 to 24 weeks at the time of this writing. All patients showed a pronounced anatomical improvement, and seven of the 11 experienced an increase in visual acuity. All reported subjective vision improvement, and no adverse events. These results confirm the high efficacy and safety of faricimab for nAMD and DME, both in treatment-naïve patients and those switched from other therapies.},
}
@article {pmid39731238,
year = {2024},
author = {Budzinskaya, MV and Plyukhova, AA and Makarova, MA and Sorokin, AP},
title = {[Management of patients with treatment-resistant neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {6},
pages = {63-68},
doi = {10.17116/oftalma202414006163},
pmid = {39731238},
issn = {0042-465X},
mesh = {Humans ; Male ; Female ; *Intravitreal Injections ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Macular Degeneration/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; Middle Aged ; Retinal Detachment/etiology/diagnosis/drug therapy ; Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; },
abstract = {PURPOSE: This study evaluates the efficacy of intravitreal injections (IVI) of faricimab in patients with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelium detachment (RPED) resistant to other anti-VEGF agents.<br><br>MATERIAL AND METHODS: The study included 61 patients (61 eyes) with nAMD previously treated with aflibercept and/or brolucizumab IVIs. Three groups were formed: group 1 received aflibercept IVI (32 eyes), group 2 received brolucizumab IVI (14 eyes), and group 3 received aflibercept followed by brolucizumab IVI (15 eyes). All patients received four monthly loading injections of faricimab (Vabysmo, F. Hoffmann-La Roche Ltd, Switzerland) at a dose of 0.05 ml (6 mg), with disease activity assessed at month 4. For active disease, injections were administered at 4-week intervals; for inactive disease, injections were done at 8-week intervals.<br><br>RESULTS: In group 1, significant improvement was observed in all parameters by month 4 (p<0.05), accompanied by an increase in visual acuity. Similar findings were recorded at month 6. In group 2, no statistically significant change in best-corrected visual acuity (BCVA) was found; however, a notable reduction in central retinal thickness and maximum RPED height was seen at both months 4 and 6, due to decrease in fibrous and fibrovascular layers (p<0.05). No signs of prechoroidal cleft were detected. In group 3, monthly IVI resulted in reductions in all parameters except prechoroidal cleft height (p>0.05), although by month 6 the values returned to baseline pre-treatment levels (p>0.05).<br><br>CONCLUSIONS: Intravitreal injections of faricimab may prove to be an effective treatment for nAMD in patients resistant to other anti-VEGF agents.},
}
@article {pmid39731231,
year = {2024},
author = {Fursova, AZ and Dmitrieva, EI and Vasilieva, MA and Derbeneva, AS and Karlash, YA and Atamanenko, AA and Nikulich, IF and Tarasov, MS},
title = {[Analysis of the effectiveness of cataract surgery in neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {6},
pages = {7-14},
doi = {10.17116/oftalma20241400617},
pmid = {39731231},
issn = {0042-465X},
mesh = {Humans ; Male ; Female ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Visual Acuity ; *Intravitreal Injections ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Phacoemulsification/methods ; Macular Degeneration/diagnosis/etiology/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Cataract/diagnosis/complications/etiology ; Aged, 80 and over ; Wet Macular Degeneration/diagnosis/drug therapy/physiopathology ; },
abstract = {PURPOSE: This study evaluated the impact of phacoemulsification cataract surgery (PE) on anatomical and functional parameters, as well as the regimen and frequency of anti-VEGF injections in patients with neovascular age-related macular degeneration (nAMD) over a long-term period (up to 3 years).<br><br>MATERIAL AND METHODS: The study included 117 patients (117 eyes) diagnosed with nAMD and cataract, graded by LOCS: LOCS I (n=56; 47.9%), LOCS II (n=57; 48.7%), LOCS III (n=4; 3.4%); the average age of the patients was 76.2&#xb1;5.7 years. All patients received anti-VEGF therapy (aflibercept 2 mg) following the treat-and-extend protocol. PE was performed only with disease activity under control. The observation period included 12 months before PE and 36 months after, with eight checkpoints for standard ophthalmological examination.<br><br>RESULTS: The average number of injections before PE was 6.85&#xb1;1.78. In the first year after PE, the injection frequency increased to 7.85&#xb1;0.83, then decreased to 7.04&#xb1;1.50 in the second year and 3.85&#xb1;1.22 in the third, with intervals between injections lengthening (to 13.35&#xb1;1.84 weeks by the third year). All eyes (100%) demonstrated significant improvement in best-corrected visual acuity (BCVA), with an absolute increase of 0.28 from pre-PE baseline (from 0.22&#xb1;0.17 to 0.50&#xb1;0.18 by study end). There was a positive trend in reduction of central retinal thickness (by 138.5 &#x3bc;m or 36.5%) compared to baseline at the start of treatment, as well as reduction in neuroretinal and retinal pigment epithelial detachment over the observation period. Statistically significant correlations were found between BCVA, injection frequency, injection interval, and morphological biomarkers of nAMD activity over time.<br><br>CONCLUSION: Initiation of antiangiogenic therapy in nAMD patients and the continuation of individualized monitoring and treatment after PE is associated with effective suppression of nAMD activity, improvement in functional and anatomical parameters, and a reduction in the number of intravitreal injections both in the short term and the long term.},
}
@article {pmid39730975,
year = {2025},
author = {Tao, BK and Xie, JS and Leung, V and Patel, M and Xu, J and Lo, C and Yan, P and Nathoo, N and Lam, WC and Navajas, EV and Muni, R and Kohly, RP},
title = {Enrolment characteristics in age-related macular degeneration clinical trials: a cross-sectional study.},
journal = {Eye (London, England)},
volume = {39},
number = {6},
pages = {1153-1159},
pmid = {39730975},
issn = {1476-5454},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Clinical Trials as Topic ; Cross-Sectional Studies ; *Macular Degeneration/therapy/epidemiology ; *Patient Selection ; Randomized Controlled Trials as Topic/statistics &amp; numerical data ; },
abstract = {BACKGROUND/OBJECTIVES: To investigate demographic enrolment characteristics in age-related macular degeneration (AMD) trials.<br><br>SUBJECTS/METHODS: Clinicaltrials.gov was searched with "age-related macular degeneration" to identify RCTs with double, triple, or quadruple masking. Trial (e.g., study location, phase, masking, trial initiation year, and sponsor origin) and patient demographic data were collected. Sex-based AMD disease burdens were retrieved from the Global Burden of Disease database to calculate pooled female population-to-prevalence ratios (PPRs). Equitable trial enrolment was defined as PPR between 0.8-1.2. Demographic proportions were evaluated across trial characteristics using the Kruskal-Wallis test (alpha&#x2009;=&#x2009;0.05) followed by post hoc comparisons. Secondary outcomes included absolute number of enrolled female, racial, and ethnic groups, and the association of trial characteristics with these demographics.<br><br>RESULTS: We included 106 trials (77,939 patients; 46.3% female), spanning 1990-2020. The pooled female PRR was 0.88 (95% confidence interval [CI]: 0.82, 0.94). PPR values were inconclusive studies with quadruple blinding; phase I, III, IV, or not applicable status; foreign (non-US) site; US-only and foreign-only sponsor; and an initiation year before 2010. There was no significant difference in PPR between sublevels of analysed trial characteristics. Of the 74 (69.8%) trials that adequately detailed race, White participants comprised the largest group (N&#x2009;=&#x2009;57,917; 82% of total participants). Thirty-seven (34.9%) trials adequately detailed ethnicity. The absolute enrolment of race and ethnic groups did not generally exhibit significant difference between sublevels of analysed trial characteristics.<br><br>CONCLUSIONS: Female enrolment was commensurate to their disease burden across all trial characteristics. Race and ethnicity were under-reported. Future trials should prioritise equitable study enrolment strategies.},
}
@article {pmid39730973,
year = {2025},
author = {Tang, X and Liu, W and Liang, J and Zhu, X and Ge, X and Fang, D and Ling, L and Yuan, F and Zeng, K and Chen, Q and Zhang, G and Gong, L and Zhang, S},
title = {Correction to: Triamcinolone Acetonide Protects Against Light-Induced Retinal Degeneration by Activating Anti-Inflammatory STAT6/Arg1 Signaling in Microglia.},
journal = {Inflammation},
volume = {48},
number = {4},
pages = {2837-2838},
doi = {10.1007/s10753-024-02224-x},
pmid = {39730973},
issn = {1573-2576},
abstract = {Microglia are highly specialized resident macrophages in the central nervous system that play a pivotal role in modulating neuroinflammation. Microglial plasticity is essential for their function, allowing them to polarize into proinflammatory M1-like or anti-inflammatory M2-like phenotypes. However, the mechanisms driving M1 and M2 microglial induction during retinal degeneration remain largely unexplored. In addition, drugs that regulate retinal microglial polarity have not been fully investigated. The synthetic glucocorticoid triamcinolone acetonide (TA) is widely utilized in ophthalmology clinics for its anti-inflammatory properties. Here, we investigated microglial polarity in a light-induced retinal degeneration mouse model, along with the effects and mechanisms of intravitreal injection of TA on microglial polarity, retinal inflammation, and visual function following light damage (LD). Our findings demonstrated that LD induced a pro-inflammatory M1 microglial signature, with levels of M1 marker proteins in the retina increasing in a time-dependent manner following LD. Intravitreal TA treatment mitigated LD-induced retinal inflammation, photoreceptor death, and retinal blood vessel leakage, and preserved retinal responsiveness to light stimuli. Mechanistically, TA suppressed the proinflammatory microglial phenotype while promoting the anti-inflammatory phenotype by activating the signal transducer and activator of transcription 6/arginase1 (STAT6/Arg1) signaling pathway. These results reveal a new mechanism by which TA protects the retina from LD by shifting microglia toward an anti-inflammatory state through the STAT6/Arg1 axis.},
}
@article {pmid39730605,
year = {2024},
author = {Sassone, F and Estay-Ahumada, C and Roux, MJ and Ciocca, D and Rossolillo, P and Birling, MC and Sparrow, JR and Montenegro, D and Hicks, D},
title = {Interruption of the visual cycle in a novel animal model induces progressive vision loss resembling Stargardts Disease.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30880},
pmid = {39730605},
issn = {2045-2322},
support = {R01 EY012951/EY/NEI NIH HHS/United States ; S10 OD028637/OD/NIH HHS/United States ; NEI EY012951//UNADEV/ITMO Aviesan 2018-2021, Fondation de France (Association Berthe Fouassier) and USIAS (DH); and NEI EY012951 (JRS)./ ; },
mesh = {Animals ; *Disease Models, Animal ; *ATP-Binding Cassette Transporters/genetics/metabolism ; *Stargardt Disease ; Humans ; Retinal Cone Photoreceptor Cells/metabolism/pathology ; Macular Degeneration/pathology/genetics/metabolism ; Electroretinography ; CRISPR-Cas Systems ; Rats ; Retina/metabolism/pathology/physiopathology ; Tomography, Optical Coherence ; Retinal Degeneration/metabolism/pathology/genetics ; },
abstract = {Mutations in the gene ABCA4 coding for photoreceptor-specific ATP-binding cassette subfamily A member 4, are responsible for Stargardts Disease type 1 (STGD1), the most common form of inherited macular degeneration. STGD1 typically declares early in life and leads to severe visual handicap. Abca4 gene-deletion mouse models of STGD1 accumulate lipofuscin, a hallmark of the disease, but unlike the human disease show no or only moderate structural changes and no functional decline. The human macula is highly enriched in cones, and reasoning that the low cone percentage in mice retinas (< 3%) might compromise faithful modelling of human maculopathies, we performed sub-retinal injections of CRISPR/Cas9-abca4 Adeno-Associated Virus constructs into young Sand Rats (Psammomys obesus), a diurnal rodent containing > 30% cones. Compared to control injections of AAV-abca4-GFP, treated eyes exhibited extensive retinal degeneration by two months. Sanger sequencing of the CRISPR targeted sequence show a clear edition of Abca4 gene. Non-invasive fundus imaging showed widespread photoreceptor loss, confirmed by ocular coherence tomography. Functional recording by single flash and flicker electroretinography showed significant decline in photopic (cone) light responses. Post-mortem real-time PCR, immunohistochemistry and western blotting showed significant decrease of cone-specific (MW cone opsin) but not rod-specific (rhodopsin) markers. Transmission electron microscopy showed large numbers of lipid inclusions in treated but not control retinal pigmented epithelium. Finally, ultra-high performance liquid chromatography analysis of whole P. obesus eyes showed the presence of all-trans retinal-dimer, not detected in rod-rich rat eyes. In conclusion, Abca4 knockout in P. obesus results in a predominantly cone degeneration phenotype, more accurately reflecting the etiology of human STGD1, and should be valuable for characterizing pathogenic pathways and exploring treatment options.},
}
@article {pmid39729520,
year = {2025},
author = {Li, H and Sharma, R and Bharti, K},
title = {iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.},
journal = {Stem cells translational medicine},
volume = {14},
number = {3},
pages = {},
pmid = {39729520},
issn = {2157-6580},
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/metabolism ; *Induced Pluripotent Stem Cells/metabolism/pathology/cytology ; *Retinal Degeneration/pathology/physiopathology/metabolism ; Phenotype ; Animals ; Macular Degeneration/pathology ; },
abstract = {Retinal pigment epithelium (RPE) atrophy is a significant cause of human blindness worldwide, occurring in polygenic diseases such as age-related macular degeneration (AMD) and monogenic diseases such as Stargardt diseases (STGD1) and late-onset retinal degeneration (L-ORD). The patient-induced pluripotent stem cells (iPSCs)-derived RPE (iRPE) model exhibits many advantages in understanding the cellular basis of pathological mechanisms of RPE atrophy. The iRPE model is based on iPSC-derived functionally mature and polarized RPE cells that reproduce several features of native RPE cells, such as phagocytosis of photoreceptor outer segments (POS) and replenishment of visual pigment. When derived from patients, iRPE are able to recapitulate critical cellular phenotypes of retinal degenerative diseases, such as the drusen-like sub-RPE deposits in the L-ORD and AMD models; lipid droplets and cholesterol accumulation in the STGD1 and AMD models. The iRPE model has helped discover the unexpected role of RPE in understanding retinal degenerative diseases, such as a cell-autonomous function of ABCA4 in STGD1. The iRPE model has helped uncover the pathological mechanism of retinal degenerative diseases, including the roles of alternate complement cascades and oxidative stress in AMD pathophysiology, abnormal POS processing in STGD1 and L-ORD, and its association with lipid accumulation. These studies have helped better understand-the role of RPE in retinal degenerative diseases, and molecular mechanisms underlying RPE atrophy, and have provided a basis to discover therapeutics to target RPE-associated diseases.},
}
@article {pmid39728032,
year = {2024},
author = {Landini, L and Boscia, G and Vidal-Aroca, F and Niro, A and Pastore, V and Piepoli, M and Viggiano, P and Grassi, MO and Giancipoli, E and Pignataro, MG and Alessio, G and Levy, MH and Sborgia, G and Boscia, F},
title = {Multifocal Electroretinography Changes in Patients with Late-Stage Age-Related Macular Degeneration (AMD) After Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT): A Case Series.},
journal = {Journal of personalized medicine},
volume = {14},
number = {12},
pages = {},
pmid = {39728032},
issn = {2075-4426},
abstract = {The smaller-incision new-generation implantable miniature telescope (SING IMT) represents an advancement over the previous model, WA-IMT, serving as a unilateral prosthetic device for patients with late-stage age-related macular degeneration (AMD). Purpose: This study aims to report changes in multifocal electroretinography (mfERG) 6 months post-SING IMT implantation. Methods: In this case series, we prospectively evaluated a cohort of phakic patients with late-stage AMD who underwent SING IMT implantation at the Ophthalmology Unit, University of Bari Aldo Moro, Italy. We assessed best-corrected distance visual acuity (BCDVA) and best-corrected near visual acuity (BCNVA) preoperatively and at 6 months postoperatively. Additionally, mfERGs were conducted using Retimax (CSO, Florence, Italy). Results: All four treated patients showed an increase in both BCDVA and BCNVA at the 6-month follow-up. Additionally, all eyes demonstrated increased P1 density at this time point, with the greatest augmentation observed at the central fixation point, gradually diminishing across the five concentric rings. While all patients displayed a general increase in P1 amplitude, the third patient exhibited a slight decrease in the foveal region. Conclusions: In this case series with four cases, the new generation implantable miniature telescope, SING IMT, demonstrates promising results in enhancing mfERG parameters in patients with late-stage AMD. Six months post-surgery, we observed an augmentation in both P1 density and amplitude, predominantly at the fixation point and gradually tapering in the surrounding concentric rings.},
}
@article {pmid39726310,
year = {2024},
author = {Chen, R and Wu, Y and Fang, Y and Lan, T and Shi, W},
title = {Plasma Extracellular Vesicle-Associated Proteins as Promising Diagnostic Biomarkers of Age-Related Macular Degeneration.},
journal = {Discovery medicine},
volume = {36},
number = {191},
pages = {2356-2364},
doi = {10.24976/Discov.Med.202436191.217},
pmid = {39726310},
issn = {1944-7930},
mesh = {Humans ; *Macular Degeneration/blood/diagnosis ; *Extracellular Vesicles/metabolism ; *Biomarkers/blood ; Female ; Aged ; Male ; ATP Binding Cassette Transporter 1/blood ; Middle Aged ; Machine Learning ; Liquid Biopsy/methods ; Case-Control Studies ; Aged, 80 and over ; Early Diagnosis ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a significant factor causing blindness in adults. However, the clinical diagnosis of AMD is relatively challenging, due to the shortcomings of the existing clinical examination methods and the latent period of retinal damage before macular degeneration becomes apparent. This study aims to explore the potential of extracellular vesicles (EVs) protein chips for early diagnosis of AMD using patients' plasma samples.<br><br>METHODS: To achieve early diagnosis of AMD, this study utilized a high-throughput platform for liquid biopsy based on EVs protein chips. Forty AMD patients and 41 normal individuals were recruited. Through machine learning methods, we identified that ATP-binding cassette transporter A1 (ABCA1) is an EVs protein marker for diagnosing AMD. Additionally, a validation set was constructed using the random forest method for verification.<br><br>RESULTS: The results of the study indicated that ABCA1 is a reliable biomarker for diagnosing AMD. The validation using the random forest method confirmed the robustness and reliability of ABCA1 as a diagnostic marker. This finding suggested that ABCA1 can serve as a new promising liquid biopsy-based marker for diagnosing macular degeneration.<br><br>CONCLUSION: The utilization of EVs protein chips, combined with machine learning methods, can effectively identify ABCA1 as a biomarker for the early diagnosis of AMD. This approach offers a promising new method for liquid biopsy diagnostics, potentially improving the clinical diagnosis and management of macular degeneration.},
}
@article {pmid39725258,
year = {2025},
author = {Thacker, M and Wong, KY and Zhou, L and Liu, J and Wong, MS},
title = {Exploring ocular disorders in Parkinson's disease: A comprehensive review and future perspectives.},
journal = {Experimental eye research},
volume = {251},
number = {},
pages = {110225},
doi = {10.1016/j.exer.2024.110225},
pmid = {39725258},
issn = {1096-0007},
mesh = {Humans ; *Parkinson Disease/complications ; *Eye Diseases/etiology/physiopathology ; Quality of Life ; },
abstract = {Parkinson's disease (PD) is a multifaceted neurodegenerative disorder characterized by predominantly motor symptoms. However, recent research has broadened our understanding of PD by revealing its impact on non-motor functions, including ocular manifestations. This review explored the intricate relationship between PD and ocular health, shedding light on the mechanisms underlying common ocular diseases such as dry eye disease, cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy. It also underscores the importance of recognizing ocular manifestations as potential early markers of PD, as well as their impact on patients' daily activities, necessitating prompt identification and intervention to prevent complications and enhance the overall quality of life. Furthermore, future research should prioritize unraveling the potential association between PD and other prevalent ocular diseases, such as myopia, to formulate effective treatment strategies.},
}
@article {pmid39724670,
year = {2025},
author = {Shughoury, A and Boucher, N and Aggarwal, N and Ciulla, TA},
title = {THREE-YEAR CLINICAL OUTCOMES IN GEOGRAPHIC ATROPHY: An Analysis of 18,712 Patient Eyes.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {2},
pages = {188-197},
doi = {10.1097/IAE.0000000000004285},
pmid = {39724670},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; *Geographic Atrophy/physiopathology/diagnosis/complications ; *Visual Acuity/physiology ; Aged ; Male ; Female ; Aged, 80 and over ; Follow-Up Studies ; *Wet Macular Degeneration/physiopathology/diagnosis/etiology/epidemiology ; Time Factors ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/therapeutic use ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To assess visual outcomes and rate of neovascular age-related macular degeneration (nAMD) development in eyes with geographic atrophy (GA).<br><br>METHODS: Retrospective analysis of 18,712 eyes with GA using the CorEvitas Vestrum Health Retina Database.<br><br>RESULTS: Mean age at index was 78.6 years (SD = 7.9) and mean visual acuity was 67.5 letters (SD = 13.0, Snellen equivalent 20/45). In total, 18.9% of eyes developed nAMD within 36 months. Eyes with fellow-eye nAMD developed nAMD at over twice the rate of eyes with fellow-eye GA (relative risk 2.34, 95% confidence interval [2.20-2.49]). Mean visual acuity of eyes that did not develop nAMD declined by 12.4 letters (95% confidence interval [12.0-12.9]) within 36 months. Older age and moderate baseline visual impairment (visual acuity <20/40-20/100) independently correlated with accelerated rate of decline. Eyes of patients in the oldest quartile with moderate visual impairment experienced the worst outcomes, losing an average of 19.7 letters over 36 months (95% confidence interval [18.1-21.3]). By 36 months, 70% of eyes had vision below threshold for driving (visual acuity &#x2264;20/40), 42% had low vision (visual acuity &#x2264;20/70), and 23% were legally blind (visual acuity &#x2264;20/200).<br><br>CONCLUSION: Geographic atrophy is associated with significant disease burden. Eyes with GA lose an average of two to three lines of visual acuity within 36 months of follow-up. Older age and moderate baseline visual impairment independently correlate with poorer visual outcomes. Presence of nAMD in the fellow eye is associated with 2-fold higher risk of exudative conversion within 36 months.},
}
@article {pmid39723875,
year = {2025},
author = {Neelamegam, V and Surya, JR and Venkatakrishnan, P and Sharma, T and Raman, R},
title = {Author's Response to comment on: Association of eGFR with stages of diabetic retinopathy and age-related macular degeneration in an Indian population.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {Suppl 1},
pages = {S177},
pmid = {39723875},
issn = {1998-3689},
}
@article {pmid39723874,
year = {2025},
author = {Yao, R and Tian, T and Yao, X},
title = {Comment on: Association of eGFR with stages of diabetic retinopathy and age-related macular degeneration in Indian population.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {Suppl 1},
pages = {S176},
pmid = {39723874},
issn = {1998-3689},
}
@article {pmid39723869,
year = {2025},
author = {Kheir, WJ and Hassoun, M and Hamam, RN and Bashshur, ZF},
title = {12-month outcomes of ziv-aflibercept for neovascular age-related macular degeneration in eyes previously treated with aflibercept.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {Suppl 1},
pages = {S78-S82},
pmid = {39723869},
issn = {1998-3689},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage ; Male ; Retrospective Studies ; Female ; *Intravitreal Injections ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Tomography, Optical Coherence/methods ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Time Factors ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Middle Aged ; Fundus Oculi ; },
abstract = {PURPOSE: To investigate the 12-month outcomes of ziv-aflibercept for neovascular age-related macular degeneration (nAMD) in eyes previously treated with aflibercept.<br><br>METHODS: Retrospective chart review of patients with nAMD previously treated with aflibercept for at least 12 months and subsequently transitioned to ziv-aflibercept between January 1, 2019, and December 31, 2022, for a period of at least 12 months. Participants were identified, and their clinical and imaging information was extracted from our electronic health records system. Data on best corrected visual acuity (BCVA), intraocular pressure, injection intervals, central retinal thickness (CRT), volume cube presence of subretinal fluid (SRF), and intraretinal fluid (IRF) were obtained. Main outcome measures included changes in BCVA, injection intervals, CRT, SRF, and IRF before and after 12 months of ziv-aflibercept treatment.<br><br>RESULTS: Fifty-four eyes of 44 patients were included in the study. After 12 months of ziv-aflibercept treatment, BCVA decreased by 0.84 ETDRS letters (P = 0.424) compared to BCVA at the last visit prior to conversion from aflibercept. Injection intervals decreased by 1.18 weeks (P = 0.489). CRT significantly decreased by 15.66 &#xb5;m (P = 0.005). SRF was present initially in 31.5% of eyes and decreased to 22.2% (P = 0.125). IRF was present initially in 42.6% of eyes and decreased to 35.2% (P = 0.219).<br><br>CONCLUSION: Ziv-aflibercept demonstrated effectiveness in maintaining treatment outcomes in nAMD eyes previously treated with aflibercept. The treatment was well-tolerated with no reported adverse events. Ziv-aflibercept may be a cost-effective alternative and a potential solution to the financial burden associated with conventional anti-VEGF agents.},
}
@article {pmid39723623,
year = {2025},
author = {Parimi, V and Elsner, AE and Papay, JA and Clark, CA and Miura, M and Gast, TJ},
title = {Photoreceptor layer elevation due to subretinal fluid: Impact on visual acuity measurements and simulation from biometrics.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {2},
pages = {480-493},
pmid = {39723623},
issn = {1475-1313},
support = {EY0R4130829//NIH NEI/ ; R44 EY030829/EY/NEI NIH HHS/United States ; R41 EY030829/EY/NEI NIH HHS/United States ; R41-EY030829/EY/NEI NIH HHS/United States ; R44AE030829//NIH NEI/ ; R44-EY030829/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Visual Acuity/physiology ; Middle Aged ; Adult ; Aged ; Male ; Female ; *Subretinal Fluid/physiology ; Young Adult ; *Biometry/methods ; *Photoreceptor Cells, Vertebrate/pathology ; *Hyperopia/physiopathology ; *Refraction, Ocular/physiology ; },
abstract = {PURPOSE: Visual acuity (VA) is a primary outcome measure that defines the success of clinical interventions for retinal diseases such as age-related macular degeneration (AMD) or diabetic macular oedema (DME). These conditions can lead to the presence of subretinal fluid, causing substantial photoreceptor layer elevation. Hyperopic defocus then occurs, affecting the VA measurements. In this study, we simulated the induced hyperopic shift for real-world values of photoreceptor layer elevation and measured the effect on VA measurements.<br><br>METHODS: To simulate the hyperopic shift, we used a four-surface eye model. To measure the effect of defocus on VA, normally sighted adults (N&#x2009;=&#x2009;44, mean [SD] age&#x2009;=&#x2009;32 [13.0] year, range: 21-71&#x2009;year) performed four test conditions, that is, defocus of 0.00, +0.75, +1.50 and +2.25 D. For each subject, mean VA and SD obtained from a cumulative normal fit to the VA data provided the coefficient of variation (CV) and 95% confidence interval (CI).<br><br>RESULTS: Refractive error induced by photoreceptor layer elevation was maximum for hyperopic error conditions, followed by emmetropic and myopic refractive error conditions. The 76% threshold VA worsened with increasing defocus conditions. The 95% CI was significantly larger for +0.75, +1.50 and +2.25 D defocus compared to no defocus (p&#x2009;=&#x2009;0.04, 0.02 and 0.01, respectively). The CI for the +2.25 D defocus condition was larger (3-10 letters) compared with no defocus (3-6 letters).<br><br>CONCLUSIONS: Photoreceptor layer elevation causes a hyperopic shift sufficient for clinically meaningful changes: worse VA and more variable measurements.},
}
@article {pmid39722646,
year = {2025},
author = {Fujii, R and Matsushita, M and Itani, Y and Hama, A and Natsume, T and Takamatsu, H},
title = {Intravitreal Administration of Avacincaptad Pegol in a Nonhuman Primate Model of Dry Age-Related Macular Degeneration.},
journal = {Pharmacology research &amp; perspectives},
volume = {13},
number = {1},
pages = {e70052},
pmid = {39722646},
issn = {2052-1707},
support = {//Hamamatsu Pharma Research/ ; },
mesh = {Animals ; *Macaca fascicularis ; Male ; *Disease Models, Animal ; *Intravitreal Injections ; *Tomography, Optical Coherence ; *Geographic Atrophy/drug therapy ; Iodates/administration &amp; dosage ; Macular Degeneration/drug therapy/pathology ; Retina/drug effects/pathology/diagnostic imaging ; Retinal Pigment Epithelium/drug effects/pathology/diagnostic imaging ; },
abstract = {The lack of effective treatments for dry age-related macular degeneration (AMD) is in part due to a lack of a preclinical animal model that recapitulates features of the clinical state including macular retinal pigment epithelium (RPE) degeneration, also known as geographic atrophy (GA). A nonhuman primate model of GA was developed and its responsiveness to an approved treatment, avacincaptad pegol (ACP), a complement C5 inhibitor, was evaluated. Intravitreal (ivt) administration of sodium iodate (SI) into one eye of male Macaca fascicularis leads to retinal areas (mm[2]) of hyper- or hypo-autofluorescence. Qualitative changes to the retinal structure over time were observed with spectral domain optical coherence tomography (OCT). Six days after SI administration, prior to treatment, mean (± SEM) GA of all eyes was 8.2 ± 1.8 mm[2]. Following randomization to treatment groups, either vehicle or ACP was ivt injected and treatment was continued every 4 weeks, for a total of four treatments. Sixteen weeks after SI administration, the GA area in vehicle-treated eyes was 18.9 ± 6.6 mm[2], whereas GA in ACP-treated eyes was 11.4 ± 4.0 mm[2], a reduction by about 36%. Increased, followed by decreased, overall macular thickness was observed with OCT over time following SI administration. Treatment with ACP did not change alter macular thickness thinning. Geographic atrophy-like lesions that expand over time are observed following SI administration. The current macaque model could be utilized to further explore the mechanism of dry AMD and to develop more novel therapeutics.},
}
@article {pmid39721968,
year = {2024},
author = {Husum, YS and Moe, MC and Fagerland, MW and Eriksen, EF and Jørstad, &#xd8;K},
title = {Zoledronic acid as adjuvant therapy in neovascular age-related macular degeneration: a randomised controlled pilot study.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {39721968},
issn = {2397-3269},
mesh = {Humans ; Pilot Projects ; *Zoledronic Acid/therapeutic use/administration &amp; dosage ; Male ; Female ; Aged ; *Visual Acuity/drug effects ; Double-Blind Method ; *Bone Density Conservation Agents/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Wet Macular Degeneration/drug therapy/physiopathology ; Aged, 80 and over ; Tomography, Optical Coherence ; Treatment Outcome ; Chemotherapy, Adjuvant/methods ; Bevacizumab/therapeutic use/administration &amp; dosage ; Fluorescein Angiography ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; },
abstract = {AIMS: To assess the feasibility of a study protocol for a randomised controlled trial of zoledronic acid (ZA) as adjuvant therapy for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: In this 1-year, randomised, double-blinded, placebo-controlled pilot study, nAMD patients were allocated 1:1 to receive intravenous ZA 5&#x2009;mg or placebo at baseline and after 6&#x2009;months in addition to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy following a treat-and-extend regimen. Bevacizumab was the first-line anti-VEGF drug, but eyes with refractory nAMD were switched to aflibercept. The primary outcome was mean change in best-corrected visual acuity (BCVA).<br><br>RESULTS: 40 participants enrolled in the study, with 20 allocated to each treatment group. 38 participants received both study infusions, and all participants completed the final assessment. Mean (SD) change in BCVA was 7.5 (9.5) letters in the ZA group and -0.5 (11.5) letters in the control group; the between-group difference was 8.0 letters (95% CI: 1.5 to 15.0 letters). There were no between-group differences in mean change in central retinal thickness, refractory nAMD proportion or mean number of injections.<br><br>CONCLUSION: It is feasible to conduct a randomised controlled trial of ZA as adjuvant therapy for nAMD in terms of recruitment and adherence to the pilot study protocol. We found a possible visual benefit of ZA that is worth further investigation. To clarify the relationship between ZA and the need for intravitreal injections, we recommend amending the protocol by omitting switching of the anti-VEGF drug. Due to the limited sample size of the pilot study, the estimates of treatment effect are not meant to be confirmatory and should be interpreted with caution.<br><br>TRIAL REGISTRATION NUMBER: 2019-001492-37 (EudraCT), 04304755 (NCT).},
}
@article {pmid39720707,
year = {2024},
author = {Medina-Arellano, AE and Albert-Garay, JS and Medina-Sánchez, T and Fonseca, KH and Ruiz-Cruz, M and Ochoa-de la Paz, L},
title = {Müller cells and retinal angiogenesis: critical regulators in health and disease.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1513686},
pmid = {39720707},
issn = {1662-5102},
abstract = {Müller cells are the most abundant glial cells in the mammalian retina. Their morphology and metabolism enable them to be in close contact and interact biochemically and physically with almost all retinal cell types, including neurons, pericytes, endothelial cells, and other glial cells, influencing their physiology by releasing bioactive molecules. Studies indicate that Müller glial cells are the primary source of angiogenic growth factor secretion in the neuroretina. Because of this, over the past decade, it has been postulated that Müller glial cells play a significant role in maintaining retinal vascular homeostasis, with potential implications in vasoproliferative retinopathies. This review aims to summarize the current understanding of the mechanisms by which Müller glial cells influence retinal angiogenesis in health and disease, with a particular emphasis on three of the retinopathies with the most significant impact on visual health worldwide: diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration.},
}
@article {pmid39720591,
year = {2024},
author = {Zhou, Y and Xue, F},
title = {Revolutionary drug repositioning: the preventive and therapeutic potential of metformin and other antidiabetic drugs in age-related macular degeneration.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1507860},
pmid = {39720591},
issn = {1663-9812},
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Anti-vascular endothelial growth factor (anti-VEGF) injections remain the first-line therapy for AMD. However, their high cost and the need for frequent administration pose challenges to long-term adherence, highlighting the need for accessible and cost-effective preventive strategies. Emerging evidence suggests that traditional antidiabetic drugs, such as metformin, sulfonylureas, and thiazolidinediones, may offer neuroprotective benefits, opening new avenues for AMD prevention. Among these, metformin has emerged as the most promising candidate, demonstrating significant potential in reducing AMD risk, even at low cumulative doses, primarily through AMP-activated protein kinase (AMPK) activation. Sulfonylureas, although effective in stimulating insulin secretion, carry risks such as hypoglycemia, hyperinsulinemia, and a possible association with increased cancer risk. Similarly, thiazolidinediones, while improving insulin sensitivity, are associated with adverse effects, including cardiovascular risks and macular edema, limiting their broader application in AMD prevention. This paper explores the preventive potential and underlying mechanisms of these antidiabetic drugs in AMD and discusses the role of artificial intelligence in optimizing individualized prevention strategies. By advancing precision medicine, these approaches may improve public health outcomes and reduce the burden of aging-related vision loss.},
}
@article {pmid39720185,
year = {2024},
author = {Lim, M and Felfeli, T and Mangubat, W and Moghimi, H and Grinton, M and Brent, MH},
title = {The Toronto Tele-Retinal Screening Program for the Elderly in Long-Term Care: A Pilot Project.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3881-3892},
pmid = {39720185},
issn = {1177-5467},
abstract = {OBJECTIVE: To report the results and feasibility of a pilot expansion of the Toronto Tele-Retinal Screening Program in an elderly long-term care home.<br><br>METHODS: Long term care patients with Type II diabetes mellitus (DM) were screened between April 1, 2022, and July 1, 2022. Demographic and health data were collected through surveys.<br><br>RESULTS: A total of 28 patients were screened, with 85.7% successfully undergoing retinal imaging. Among imaged patients, 8.3% (2/24) required urgent follow-up. Pathologies identified included uncontrolled glaucoma (4.1%, 1/24), non-proliferative diabetic retinopathy (8.3%, 2/24), and age-related macular degeneration (45.8%, 11/24). The handheld camera successfully screened 60% (3/5) of patients with mobility issues. Overall, 90% (17/19) of patients rated their experience as either "brilliant" or "really good".<br><br>DISCUSSION: This pilot project demonstrated the necessity for routine eye care in the elderly and the potential for widespread implementation of teleophthalmology in long-term care facilities. With only 14.3% (4/28) of patients unable to be imaged, this program offers a feasible, patient-friendly alternative to in-clinic screening. Future policies and practices in teleophthalmology should consider the unique needs of long-term care residents and the potential for reducing healthcare disparities through such a program.},
}
@article {pmid39719503,
year = {2025},
author = {Xue, CC and Nusinovici, S and Yu, M and Chee, ML and Teo, K and Su, X and Cheung, CMG and Sabanayagam, C and Cheng, CY and Tham, YC},
title = {Associations between shorter leucocyte telomere length and increased risk of age-related macular degeneration in women: insights from the United Kingdom Biobank study.},
journal = {Eye (London, England)},
volume = {39},
number = {6},
pages = {1146-1152},
pmid = {39719503},
issn = {1476-5454},
support = {NMRC/LCG/004/2018; NMRC/MOH/ HCSAINV21nov-0001//Ministry of Health -Singapore (MOH)/ ; },
mesh = {Humans ; Female ; Cross-Sectional Studies ; United Kingdom/epidemiology ; *Macular Degeneration/genetics/epidemiology ; *Leukocytes/metabolism/pathology ; Middle Aged ; Aged ; Male ; Risk Factors ; *Telomere/genetics ; Biological Specimen Banks ; *Telomere Shortening ; },
abstract = {OBJECTIVES: To determine the association between telomere length (TL) and age-related macular degeneration (AMD) and examine the potential variations with sex and ethnicity.<br><br>METHODS: Population-based, cross-sectional study. A total of 52,083 participants from the UK Biobank were included. Leucocyte TL, measured using quantitative polymerase chain reaction assay, was presented as the ratio of telomere repeat copy number relative to that of a single copy gene, and then log-transformed and Z-standardised. AMD cases were identified based on a combination of in-patient, self-reported and primary care data, and furtherly classified as early, intermediate and late AMD using the Beckmann classification system (based on more severe eye).<br><br>RESULTS: Among the 52,083 participants aged 60.2&#x2009;&#xb1;&#x2009;5.4 years, 725 were any-AMD cases. AMD patients had shorter TL than those without AMD (-0.22&#x2009;&#xb1;&#x2009;0.95 vs. -0.10&#x2009;&#xb1;&#x2009;0.99, P&#x2009;=&#x2009;0.001). In multivariable model, shorter TL (per standard deviation) was significantly associated with higher odds of AMD in Whites (OR:1.09; 95% CI: 1.01-1.18; P&#x2009;=&#x2009;0.036). When stratified by sex and ethnicity, this association was only significant in White women (OR:1.14; 95%CI: 1.02, 1.27; P&#x2009;=&#x2009;0.018), but not in men and nonwhite populations (all P&#x2009;&#x2265;&#x2009;0.335). Among white women, the association was more pronounced (OR:1.47; 95%CI:1.23-1.77; P&#x2009;<&#x2009;0.001) for intermediate/late AMD but not for early AMD (P&#x2009;=&#x2009;0.789).<br><br>CONCLUSIONS: Shorter TL was associated with any AMD in white women but not in men and other ethnicities. Our findings highlight the potential role of telomere length in the pathogenesis of AMD and the importance of considering sex and ethnicity variation in this research area.},
}
@article {pmid39719502,
year = {2025},
author = {Bailey, C and Chandran, M and Gale, R and Narendran, N and Talks, J and McGoey, H and Keshk, Z and Morgan-Warren, P and Allmeier, H and Machewitz, T and Patel, PJ and Varma, D},
title = {2-year results from an observational study of proactive treatment regimens with intravitreal aflibercept 2 mg in patients with nAMD in clinical practice: XTEND study UK cohort.},
journal = {Eye (London, England)},
volume = {39},
number = {6},
pages = {1138-1145},
pmid = {39719502},
issn = {1476-5454},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use/antagonists &amp; inhibitors ; Intravitreal Injections ; Female ; Aged ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage ; Prospective Studies ; Visual Acuity/physiology ; United Kingdom/epidemiology ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Follow-Up Studies ; },
abstract = {OBJECTIVES: The 36-month XTEND (NCT03939767) multicentre, observational, prospective study examined the effectiveness of proactive treatment regimens of intravitreal aflibercept (IVT-AFL) 2 mg in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. The 12- and 24-month outcomes from the XTEND UK cohort are reported.<br><br>METHODS: Patients aged &#x2265;50 years with nAMD planned to receive IVT-AFL 2&#x2009;mg were eligible. After three initial monthly IVT-AFL injections, treatment intervals could be extended in 2- to 4-weekly increments to a maximum of 16 weeks (8-week minimum treatment interval). Endpoints included mean change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at month (M) 12 and M24. Treatment intervals and safety were assessed. Statistics were descriptive.<br><br>RESULTS: In the UK, 496 patients from 23 centres were treated (mean age 79.7 years, 64.3% female). From a baseline BCVA (mean&#x2009;&#xb1;&#x2009;SD) of 55.2&#x2009;&#xb1;&#x2009;15.8 letters, mean (95% confidence interval [CI]) change in BCVA was +3.4 (2.0, 4.9) letters at M12 and +1.3 (-&#x2009;0.3, 2.9) letters at M24. From a baseline CST (mean&#x2009;&#xb1;&#x2009;SD) of 395&#x2009;&#xb1;&#x2009;143 &#x3bc;m, mean (95% CI) change in CST was -105 (&#x2009;121, -89) &#x3bc;m at M12 and -105 (-&#x2009;122, -88) &#x3bc;m at M24. By M12 and M24, patients had received a mean&#x2009;&#xb1;&#x2009;SD of 7.4&#x2009;&#xb1;&#x2009;2.4 and 10.7&#x2009;&#xb1;&#x2009;4.6 injections, respectively. Outcomes in patients enrolled prior to and during the COVID-19 pandemic were comparable. No new safety concerns were identified.<br><br>CONCLUSIONS: Despite the COVID-19 pandemic, patients in the UK achieved and maintained clinically meaningful improvements in functional and anatomic outcomes through M24.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03939767.},
}
@article {pmid39719382,
year = {2024},
author = {Wu, J and Zhang, M and Sun, X},
title = {Analysis of biofluid metabolomic profiles to the discovery of biomarkers in age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {39719382},
issn = {2397-3269},
mesh = {Humans ; *Metabolomics/methods ; *Macular Degeneration/genetics/metabolism/diagnosis ; *Biomarkers/metabolism ; Metabolome ; Body Fluids/metabolism/chemistry ; },
abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is one of the leading causes of irreversible visual impairment and blindness in the elderly. As AMD is a multifactorial disease, it is critical to explore useful biomarkers and pathological pathways underlying it. The purpose of this study is to summarise current metabolic profiles and further identify potential metabolic biomarkers and therapeutic targets in AMD, which could facilitate clinical diagnosis and treatment.<br><br>METHODS AND ANALYSIS: Relevant metabolomics studies published before 10 December 2021 were generally reviewed from online resources by two investigators. Studies with sufficient information and data were included in this systematic review and repeatedly identified metabolites were extracted. Pathway and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were performed. The public Gene Expression Omnibus (GEO) database was used for coanalysis with differential metabolites to construct a pathway network via MetaboAnalyst V.5.0.<br><br>RESULTS: 16 studies were included in our analysis. 24 metabolites were repeatedly detected and regarded as potential biomarkers for AMD. Pathway analysis implied a major role of phenylalanine, tyrosine and tryptophan pathways in AMD pathology. 11 KEGG pathways were enriched, meanwhile, 11 metabolic pathway clusters were identified by coanalysing the differential metabolites and gene profiles using the GEO database.<br><br>CONCLUSION: In this study, we summarised 16 metabolomic studies on AMD, and 24 metabolites were identified as potential biofluid biomarkers. This provided novel insights into the pathogenic mechanisms underlying AMD. Further studies are warranted to validate and expand an effective pattern for AMD diagnosis and treatment.},
}
@article {pmid39719232,
year = {2025},
author = {Zhong, Y and Zhou, Y and Jing, Z and Liu, X and Yang, K and Ren, G and Chen, H and Jiang, S and Shen, X and Du, X and Liu, H and Pan, Y and Ma, X},
title = {The effect of molecular chaperone mediated autophagy on ApoE expression in retinal pigment epithelial cells: Molecular structure and protein action mechanism.},
journal = {International journal of biological macromolecules},
volume = {291},
number = {},
pages = {139077},
doi = {10.1016/j.ijbiomac.2024.139077},
pmid = {39719232},
issn = {1879-0003},
mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; *Chaperone-Mediated Autophagy ; Humans ; *Apolipoproteins E/metabolism/genetics/chemistry ; *Molecular Chaperones/metabolism ; Lysosomes/metabolism ; Lysosomal-Associated Membrane Protein 2/metabolism/genetics ; Cell Survival/drug effects ; *Epithelial Cells/metabolism ; Cell Line ; Gene Expression Regulation ; *Autophagy ; },
abstract = {Chaperone mediated autophagy (CMA) represents a specialized mechanism of lysosomal protein breakdown, playing a crucial role as a metabolic pathway that helps to regulate and sustain cellular and systemic physiological equilibrium. Within the CMA process, proteins that contain sequences similar to KFERQ are specifically identified by the heat shock cognate protein 70. These proteins are then chaperoned to the lysosomes for subsequent degradation, a process facilitated by the lysosome associated membrane protein 2A. This particular research employed bioinformatics techniques to systematically screen for potential substrates of CMA. ApoE has a KFERQ like motif, which may be a substrate for CMA. Under conditions of starvation, hypoxia, H2O2, PA, and NaIO3, the expression of the rate limiting factor LAMP2A in CMA and ApoE increased significantly (P < 0.05). Under conditions of NaIO3, the expression of CMA related gene mRNA increased significantly (P < 0.05). When we use lysosomal blocker CQ to inhibit CMA activity, the expression level of ApoE in retinal pigment epithelial cells increased, and the difference was statistically significant (P < 0.05). When we inhibit CMA, the accumulation of ApoE in retinal pigment epithelial cells increases and cell viability decreases. When we activate CMA, the accumulation of ApoE decreases and cell viability increases. In retinal pigment epithelial cells, the drusen associated protein ApoE can be degraded through the CMA pathway.},
}
@article {pmid39718218,
year = {2025},
author = {Liu, X and Zhao, Z and Li, W and Ren, M and Zhang, H and Cao, D and Wang, Y and Yang, H and Li, Y and Zhu, M and Xie, L and Yin, L},
title = {Rationally Engineering Pro-Proteins and Membrane-Penetrating α‑Helical Polypeptides for Genome Editing Toward Choroidal Neovascularization Treatment.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {37},
number = {6},
pages = {e2412366},
doi = {10.1002/adma.202412366},
pmid = {39718218},
issn = {1521-4095},
support = {BK20220245//Natural Science Foundation of Jiangsu Province/ ; 82241008//National Natural Science Foundation of China/ ; 52325305//National Natural Science Foundation of China/ ; 52273144//National Natural Science Foundation of China/ ; 52303200//National Natural Science Foundation of China/ ; BE2021642//Jiangsu Key Research and Development Plan/ ; //Collaborative Innovation Center of Suzhou Nano Science &amp; Technology/ ; //111 project/ ; //Joint International Research Laboratory of Carbon-Based FunctionalMaterials and Devices/ ; //Suzhou Key Laboratory of Nanotechnology and Biomedicine/ ; },
mesh = {*Choroidal Neovascularization/therapy/genetics/pathology ; Animals ; *Gene Editing/methods ; Humans ; Mice ; *Peptides/chemistry ; *Protein Engineering ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Protein Conformation, alpha-Helical ; CRISPR-Cas Systems ; Ribonucleoproteins/chemistry/metabolism ; },
abstract = {Ribonucleoprotein (RNP)-based CRISPR/Cas9 genome editing holds great potential for the treatment of choroidal neovascularization (CNV), which however, is challenged by the lack of efficient cytosolic protein delivery tools. Herein, reversibly-phosphorylated pro-proteins (P-proteins) with conjugated adenosine triphosphate (ATP) tags are engineered and coupled with a membrane-penetrating, guanidine-enriched, α-helical polypeptide (LGP) to mediate robust and universal cytosolic delivery. LGP forms salt-stable nanocomplexes (NCs) with P-proteins via electrostatic interaction and salt bridging, and the helix-assisted, strong membrane activities of LGP enabled efficient cellular internalization and endolysosomal escape of NCs. Therefore, this approach allows efficient cytosolic delivery of a wide range of protein cargoes and maintains their bioactivities due to endolysosomal acidity-triggered traceless restoration of P-proteins. Notably, intravitreally delivered LGP/P-RNP NCs targeting hypoxia-inducible factor-1α (HIF-1α) induce pronounced gene disruption to downregulate pro-angiogenic factors and alleviate subretinal fibrosis, ultimately provoking robust therapeutic efficacy in CNV mice. Such a facile and versatile platform provides a powerful tool for cytosolic protein delivery and genome editing, and it holds promising potential for the treatment of CNV-associated diseases, such as age-related macular degeneration.},
}
@article {pmid39717563,
year = {2024},
author = {Aldokhail, LS and Alhadlaq, AM and Alaradi, LM and Alaradi, LM and AlShaikh, FY},
title = {Outcomes of Anti-VEGF Therapy in Eyes with Diabetic Macular Edema, Vein Occlusion-Related Macular Edema, and Neovascular Age-Related Macular Degeneration: A Systematic Review.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3837-3851},
pmid = {39717563},
issn = {1177-5467},
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management of various ocular conditions, including diabetic macular edema (DME), retinal vein occlusion (RVO)-related macular edema (ME), and neovascular age-related macular degeneration (nAMD). However, there remains a need to systematically assess its effectiveness across these distinct conditions.<br><br>METHODOLOGY: A systematic review was conducted to identify studies evaluating the efficacy of anti-VEGF therapy in improving ocular outcomes in patients with DME, RVO-related ME, and nAMD. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published up to 2024. Studies meeting the inclusion criteria were critically appraised, and data on the proportion of patients gaining &#x2265;15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in best-corrected visual acuity (BCVA), mean change in BCVA (ETDRS letters), and reduction in central macular thickness (CMT) (&#x3bc;m) were extracted and synthesized.<br><br>RESULTS: The systematic review identified 18 studies comprising randomized controlled trials, prospective studies, retrospective analyses, and observational studies. Anti-VEGF therapy demonstrated efficacy across all three conditions, with varying proportions of patients experiencing improvements in BCVA and reductions in CMT. Notably, the proportion of patients gaining &#x2265;15 ETDRS letters ranged from 18.1% to 44.8% in DME, while mean changes in BCVA ranged from +4.2 letters to +21.4 letters in RVO-related ME and nAMD. Reductions in CMT ranged from 183.1&#xa0;&#x3bc;m to 294&#xa0;&#x3bc;m in DME and RVO-related ME.<br><br>CONCLUSION: Anti-VEGF therapy represents a cornerstone in the management of DME, RVO-related ME, and nAMD, with significant improvements observed in BCVA and reductions in CMT across diverse patient populations. While our findings support the effectiveness of anti-VEGF therapy in improving ocular outcomes, further research is warranted to compare its efficacy with alternative treatment modalities and to elucidate its long-term safety profile.},
}
@article {pmid39717561,
year = {2024},
author = {LoBue, SA and Albear, S and Martin, C and Guagliardo, A and Chang, T},
title = {The Association of Primary Open Angle Glaucoma and Ocular Hypertension with Anti-VEGF Injections.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3861-3870},
pmid = {39717561},
issn = {1177-5467},
abstract = {PURPOSE: To study the effects of anti-VEGF injections on the prevalence of ocular hypertension (OHT), sustained elevated intraocular pressure (SE-IOP), and primary open-angle glaucoma (POAG) with age-matched controls.<br><br>METHODS: A retrospective case-control study was performed with neovascular age-related macular degeneration (AMD) or diabetic macular edema (DME) against a control group involving atrophic AMD or diabetic retinopathy (DR) without DME. Bevacizumab, ranibizumab, or a combination of both were used in the treatment group. OHT was defined as IOP>21 mm Hg while SE-IOP was defined as IOP that increased by > 6&#xa0;mmHg or was >25 mm Hg on two or more visits, 30 days apart. Patients with a pre-existing history of glaucoma, vein occlusions, IVI steroids, and pars plana vitrectomy were excluded.<br><br>RESULTS: A total of 1312 eyes of 784 patients were included in the study. Using age-matched controls, the treatment and control group was further refined to 394 eyes of 224 patients compared to 340 eyes from 170 patients respectively. The mean age was 58.4 &#xb1; 8.7 for the control versus 58.8 &#xb1; 8.8 years for the treatment group. The average IOP was higher in the injection group compared to the control with 25.8 &#xb1; 9.3 versus 19.5 &#xb1; 5.1&#xa0;mmHg respectively, P<0.001. Significant increases in POAG (10.7% vs 2.9%, p<0.01), OHT (67.0% vs 22.4%, p<0.001), and SE-IOP (41.1% vs 7.6%, p<0.001) were seen in the injection group compared to the age-matched control group. The rates of POAG and OHT were positively associated with the number of injections, R[2]=0.856, P<0.01 and R[2]=0.749, P<0.05, respectively.<br><br>CONCLUSION: Compared to age-matched controls, patients treated with anti-VEGF agents demonstrated an increased rate of OHT, SE-IOP, and POAG which correlated with the number of IVIs. However, additional prospective studies are needed to determine if there is a true association between intravitreal anti-VEGF injections and glaucoma.},
}
@article {pmid39716681,
year = {2025},
author = {Lakkaraju, A and Boya, P and Csete, M and Ferrington, DA and Hurley, JB and Sadun, AA and Shang, P and Sharma, R and Sinha, D and Ueffing, M and Brockerhoff, SE},
title = {How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.},
journal = {Experimental eye research},
volume = {251},
number = {},
pages = {110219},
pmid = {39716681},
issn = {1096-0007},
support = {R01 EY006641/EY/NEI NIH HHS/United States ; R01 EY026020/EY/NEI NIH HHS/United States ; R01 EY033731/EY/NEI NIH HHS/United States ; R01 EY035514/EY/NEI NIH HHS/United States ; R01 EY028554/EY/NEI NIH HHS/United States ; R01 EY030668/EY/NEI NIH HHS/United States ; U01 EY034669/EY/NEI NIH HHS/United States ; R01 EY017863/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Lysosomes/metabolism/physiology ; *Mitochondria/metabolism/physiology ; *Retinal Pigment Epithelium/metabolism ; *Geographic Atrophy/metabolism/prevention &amp; control ; Oxidative Stress/physiology ; Animals ; *Macular Degeneration/metabolism ; Peroxisomes/metabolism ; },
abstract = {Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE). However, how these occur, and how they relate to organelle function both with the RPE and potentially the photoreceptors are fundamental, unresolved questions in AMD biology. Here, we report the discussions of the "Mitochondria, Lysosomes, and other Organelle Interactions" task group of the 2024 Ryan Initiative for Macular Research (RIMR). Our group focused on understanding the interplay between cellular organelles in maintaining homeostasis in the RPE and photoreceptors, how this could be derailed to promote AMD, and identifying where these pathways could potentially be targeted therapeutically.},
}
@article {pmid39716627,
year = {2025},
author = {M, K and G, M},
title = {A comprehensive review on early detection of drusen patterns in age-related macular degeneration using deep learning models.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {51},
number = {},
pages = {104454},
doi = {10.1016/j.pdpdt.2024.104454},
pmid = {39716627},
issn = {1873-1597},
mesh = {Humans ; *Deep Learning ; *Retinal Drusen/diagnostic imaging/diagnosis ; *Macular Degeneration/diagnostic imaging/diagnosis ; Early Diagnosis ; },
abstract = {Age-related Macular Degeneration (AMD) is a leading cause of visual impairment and blindness that affects the eye from the age of fifty-five and older. It impacts on the retina, the light-sensitive layer of the eye. In early AMD, yellowish deposits called drusen, form under the retina, which could result in distortion and gradual blurring of vision. The presence of drusen is the first sign of early dry AMD. As the disease progresses, more and larger deposits develop, and blood vessels grow up from beneath the retina leading to leakage of blood, that damages the retina. In advanced AMD, peripheral vision may remain, but the straight vision is lost. Detecting AMD early is crucial, but treatments are limited, and nutritional supplements like AREDS2 formula may slow disease progression. AMD diagnosis is primarily achieved through drusen identification, a process involving fundus photography by ophthalmologists, but the early stages of AMD make this task challenging due to ambiguous drusen regions. Furthermore, the existing models have difficulty in correctly predicting the drusen regions because of the resolution of fundus images, for which a solution is proposed as a model based on deep learning. Performance can be optimized by employing both local and global knowledge when AMD issues are still in the early phases. The area of the retina where drusen forms were identified by image segmentation, and then these deposits were automatically recognized through pattern recognition techniques.},
}
@article {pmid39713956,
year = {2025},
author = {Zhu, X and Huang, Y and Liang, L and Zhang, X and Zhang, Z and Jiang, Y and Wu, X and Li, C and Zheng, Z and Bao, Z and Zou, W and Zhao, S},
title = {Frailty and the Risk of Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Study.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {80},
number = {3},
pages = {},
doi = {10.1093/gerona/glae300},
pmid = {39713956},
issn = {1758-535X},
support = {82271111//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/epidemiology/genetics/etiology ; Male ; Female ; Aged ; *Frailty/complications/epidemiology ; Prospective Studies ; Risk Factors ; Middle Aged ; United Kingdom/epidemiology ; Phenotype ; Proportional Hazards Models ; *Frail Elderly ; Aged, 80 and over ; },
abstract = {BACKGROUND: Both frailty and age-related macular degeneration (AMD) are related to aging and may share some common mechanisms. We aimed to examine the observational and causal association between frailty and the risk of AMD.<br><br>METHODS: We included 320&#x2005;810 participants free of AMD at baseline from the UK Biobank. Frailty phenotypes were defined according to 5 components: weight loss, exhaustion, slow gait speed, low grip strength, and low physical activity. Cox proportional hazard models were used to evaluate the association between frailty phenotype and the risk of AMD. A causal relationship between frailty phenotype and AMD was examined using 2-sample Mendelian randomization (MR) analysis.<br><br>RESULTS: During a median follow-up of 12.81 years, 7&#xa0;222 AMD cases were documented. After adjusting for confounding factors, compared with nonfrail participants, both pre-frail and frail participants were significantly associated with an increased risk of AMD (hazard ratio [HR] 1.17, [95% confidence interval {CI}
: 1.11, 1.23] for pre-frailty and HR 1.55 [95% CI: 1.40, 1.73] for frailty). With each 1-point increase in frailty phenotype score, the risk of AMD increased by 14%. Results from the 2-sample MR analysis supported the potential causal effect of frailty phenotype on AMD.<br><br>CONCLUSIONS: Our findings suggested that frailty assessment may help identify at-risk populations and serve as a potential strategy for early prevention and management of AMD.},
}
@article {pmid39712068,
year = {2024},
author = {Hultgren, NW and Petcherski, A and Torriano, S and Komirisetty, R and Sharma, M and Zhou, T and Burgess, BL and Ngo, J and Osto, C and Shabane, B and Shirihai, OS and Kelesidis, T and Williams, DS},
title = {Productive infection of the retinal pigment epithelium by SARS-CoV-2: Initial effects and consideration of long-term consequences.},
journal = {PNAS nexus},
volume = {3},
number = {12},
pages = {pgae500},
pmid = {39712068},
issn = {2752-6542},
support = {R01 AG059502/AG/NIA NIH HHS/United States ; },
abstract = {As the SARS-CoV-2 coronavirus continues to evolve and infect the global population, many individuals are likely to suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Manifestations of PASC include vision symptoms, but little is known about the ability of SARS-CoV-2 to infect and impact the retinal cells. Here, we demonstrate that SARS-CoV-2 can infect and perturb the retinal pigment epithelium (RPE) in vivo, after intranasal inoculation of a transgenic mouse model of SARS-CoV-2 infection, and in cell culture. Separate lentiviral studies showed that SARS-CoV-2 Spike protein mediates viral entry and replication in RPE cells, while the Envelope and ORF3a proteins induce morphological changes. Infection with major variants of SARS-CoV-2 compromised the RPE barrier function and phagocytic capacity. It also caused complement activation and production of cytokines and chemokines, resulting in an inflammatory response that spread across the RPE layer. This inflammatory signature has similarities to that associated with the onset of age-related macular degeneration (AMD), a major cause of human blindness, resulting from RPE pathology that eventually leads to photoreceptor cell loss. Thus, our findings suggest that post-acute sequelae of SARS-CoV-2 infection of the RPE may have long-term implications for vision, perhaps comparable to the increased occurrence of AMD found among individuals infected by HIV, but with greater public health consequences due to the much larger number of SARS-CoV-2 infections.},
}
@article {pmid39710905,
year = {2025},
author = {Rodriguez, DA and Song, A and Bhatnagar, A and Weng, CY},
title = {Photobiomodulation Therapy for Non-exudative Age-related Macular Degeneration.},
journal = {International ophthalmology clinics},
volume = {65},
number = {1},
pages = {47-52},
pmid = {39710905},
issn = {1536-9617},
mesh = {Humans ; *Low-Level Light Therapy/methods ; *Macular Degeneration/radiotherapy/therapy ; Visual Acuity ; },
abstract = {Age-related macular degeneration (AMD) is a chronic condition that causes gradual central vision loss, most commonly in patients 50 years or older. This disease is commonly classified as either dry (non-exudative) or wet (exudative). Most patients with AMD have the non-exudative form, characterized by the presence of drusen in the macula. These patients can be further subclassified based on drusen size into early, intermediate, or late stages. The pathogenesis of this disease is quite complex and has been linked to genetic variations, dysfunction of normal retinal homeostasis, chronic inflammation, and mitochondrial dysfunction. Current treatment options for patients with intermediate dry AMD are limited to lifestyle modifications and vitamin supplementation. Photobiomodulation therapy (PBT) has been proposed as an additional therapy for this disease. Early animal and human studies have shown that PBT can alter many of the pathways implicated in the pathogenesis of AMD including improving mitochondrial function, decreasing inflammation, and promoting wound healing. Clinical trials investigating the use of PBT in patients with non-exudative AMD have shown promising results. Many of these trials showed improvement in both clinical (visual acuity and contrast sensitivity) as well as anatomic (drusen volume and area geographic atrophy) variables. Most, however, are limited by sample size, differences in treatment algorithm, and populations tested. Ongoing clinical trials aim to expand on this work with longer follow-up, larger sample sizes, and studying a global population. Further work is needed to determine ideal treatment algorithms and patient populations that may benefit the most from this technology.},
}
@article {pmid39710904,
year = {2025},
author = {Bordbar, DD and Bhatnagar, A and Weng, CY},
title = {Use of Home Optical Coherence Tomography for Retinal Diseases.},
journal = {International ophthalmology clinics},
volume = {65},
number = {1},
pages = {41-46},
doi = {10.1097/IIO.0000000000000546},
pmid = {39710904},
issn = {1536-9617},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnostic imaging ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; },
abstract = {Modern treatment protocols for retinal diseases involve frequent in-office monitoring with optical coherence tomography (OCT) and treatment with anti-vascular endothelial growth factor injections. Monthly injections may yield the greatest visual outcomes but are the most burdensome for patients and physicians, while as-needed injections may lead to undertreatment. Hybrid protocols, such as treat-and-extend (TREX) have been conceived to bridge this gap. Device-based home monitoring protocols for retinal disease may iterate further and allow more precise treatment tailored to individualized disease activity curves. Prior non-OCT home monitoring strategies have been developed with varying efficacy. These range from the ubiquitous but low-sensitivity Amsler grid to recent innovations such as the ForeseeHome preferential hyperacuity perimeter. Most recently, home OCT devices have been studied for remote monitoring, largely for use with age-related macular degeneration (AMD). Currently, the only Food and Drug Administration (FDA) approved device that utilizes OCT for monitoring retinal disease is the SCANLY Home OCT. Paired with an artificial intelligence (AI) algorithm that allows automated monitoring and alerting of retinal fluid volumes in AMD, SCANLY has demonstrated feasibility in limited trials to date, and a multicenter randomized controlled trial is currently underway to assess its efficacy in comparison to TREX regimens. Additional non-FDA-approved devices are being developed with varying degrees of study to date. Questions remain regarding its efficacy, real-world implementation, and financial considerations; nevertheless, home OCT has the potential to address many current barriers in retinal care, including travel and treatment burdens, while facilitating increased treatment precision.},
}
@article {pmid39710899,
year = {2025},
author = {Ravichandran, P and Canizela, C and Sayed, A and Hussain, RM},
title = {Tyrosine Kinase Inhibitors: The Next Chapter in Reducing Treatment Burden for Exudative Retinal Diseases?.},
journal = {International ophthalmology clinics},
volume = {65},
number = {1},
pages = {9-15},
pmid = {39710899},
issn = {1536-9617},
mesh = {Humans ; *Protein Kinase Inhibitors/therapeutic use ; Retinal Diseases/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Protein-Tyrosine Kinases/antagonists &amp; inhibitors ; Tyrosine Kinase Inhibitors ; },
abstract = {Tyrosine kinase inhibitors (TKIs) serve to inhibit the phosphorylation cascade that usually leads to abnormal processes such as vascular leakage and tumorigenesis. Within retinal diseases specifically, dysregulation of the vascular endothelial growth factor receptor tyrosine kinases can lead to age-related macular degeneration and diabetic macular edema. These diseases have a growing prevalence and are leading causes of vision loss. The current standard of care requires repeated administration of anti-vascular endothelial growth factor injections, which poses a significant burden on patients. Novel TKIs provide an opportunity to reduce injection frequency by targeting a broader range of molecules involved in angiogenesis and exudation. This review will cover TKIs in development and how their use of different technologies and targets may enhance visual and anatomic outcomes for patients with exudative retinal disease.},
}
@article {pmid39710898,
year = {2025},
author = {Khanani, I and Aziz, AA and Khanani, ZA and Khan, H and Mojumder, O and Sulahria, H and Ali, H and Khan, H and Rahimzadeh, TS and Vannavong, J and Gahn, GM and Khanani, AM},
title = {The Safety of Recently Approved Therapeutics in Age-Related Macular Degeneration.},
journal = {International ophthalmology clinics},
volume = {65},
number = {1},
pages = {3-7},
pmid = {39710898},
issn = {1536-9617},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/adverse effects ; *Drug Approval ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {Recent developments in treatments for both forms of advanced age-related macular degeneration (AMD) have led to the approval of multiple agents and modalities within the last few years. Five new medications for both neovascular AMD (nAMD) and geographic atrophy (GA) secondary to nonexudative AMD (neAMD) have been FDA-approved within the last 5 years, along with a new device designed for sustained drug delivery for nAMD. In nAMD, the newest agents approved by the FDA are brolucizumab (Novartis Pharmaceuticals, Basel, Switzerland), faricimab (F. Hoffman-La Roche, Basel, Switzerland), aflibercept 8 mg (Regeneron Pharmaceuticals, Tarrytown, NY, USA), and a new device in the port delivery system with ranibizumab (Genentech, San Francisco, CA, USA). The first agents FDA-approved for GA secondary to neAMD are pegcetacoplan (Apellis Pharmaceuticals, Waltham, MA, USA) and avacincaptad pegol (Iveric Bio, Parsippany, NJ, USA). Evaluation of safety in both clinical trials and the real-world has been of paramount importance after the approval of these newest agents to understand their effects in real patients. Real-world data, as demonstrated in both registrational studies along with retrospective chart review studies, has shown to be an important factor in the implementation of newer drugs, along with the treatment decisions that physicians choose to make regarding their dosing and follow-up. This review article discusses the safety of the most recently approved FDA as seen in both clinical trials and real-world studies.},
}
@article {pmid39710756,
year = {2024},
author = {Chen, J and Lu, T and Chen, C and Zheng, W and Lu, L and Li, N},
title = {Elevation of ANXA1 associated with potential protective mechanism against ferroptosis and immune cell infiltration in age-related macular degeneration.},
journal = {European journal of medical research},
volume = {29},
number = {1},
pages = {615},
pmid = {39710756},
issn = {2047-783X},
support = {2023M734071//China Postdoctoral Science Foundation/ ; },
mesh = {*Ferroptosis/genetics ; *Macular Degeneration/genetics/immunology/pathology/metabolism ; Animals ; Mice ; Humans ; *Annexin A1/genetics/metabolism ; Protein Interaction Maps/genetics ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD), is a neurodegenerative ocular disease. This study investigated the role of ferroptosis-related genes and their interaction with immune cell infiltration in AMD.<br><br>METHODS: We screened differential expression genes (DEGs) of AMD from data sets in Gene Expression Omnibus. We identified ferroptosis-related differentially expressed genes (ferroDEGs) by intersecting DEGs with ferroptosis-related genes. Protein-protein interactions network and Cytoscape were used for screening hub genes. Next, we analyzed immune cell infiltration using CIBERSORT and examined the crosstalk between hub ferroDEGs and immune cell infiltration. Hub genes expression in each cell cluster and the proportions of different cell clusters between AMD and normal samples were examined using single-cell data. The hub ferroDEG expressions were verified in cell and mouse models using RT-qPCR, western blot, and immunofluorescence assay. The roles of ANXA1 in ferroptosis and its crosstalk with microglia were investigated.<br><br>RESULTS: We identified hub ferroDEGs that include six genes (ANXA1, DKK1, CD44, VIM, TGFB2, DUSP1). Functional analysis of those hub ferroDEGs was found to be correlated with leukocyte migration and chemotaxis, macrophage migration, and gliogenesis. The high-risk ferroptosis group exhibited elevated levels of CD8[+] T cells, activated NK cells, and M2 macrophages. Single-cell sequencing data revealed a high degree of cell heterogeneity in macular degeneration and the monocytes proportion in the macular area was higher in AMD samples. Moreover, we observed elevated mRNA and protein levels of CD44, ANXA1 (P&#x2009;<&#x2009;0.01), while ANXA1 knockdown reduced GPX4 expression in the cell model. Finally, we validated increased ANXA1 expression and observed its colocalization with microglia in mouse models using immunofluorescence assays.<br><br>CONCLUSIONS: This study offers insights into the AMD pathogenesis and identifies ANXA1 as a potential target related to protecting from ferroptosis and immune response for future research.},
}
@article {pmid39710749,
year = {2024},
author = {Shmueli, O and Sutter, D and Levy, J and Fagan, X},
title = {Near-infrared imaging retinal diagnostic applications-a review.},
journal = {International ophthalmology},
volume = {45},
number = {1},
pages = {20},
pmid = {39710749},
issn = {1573-2630},
mesh = {Humans ; *Retinal Diseases/diagnosis/diagnostic imaging ; Tomography, Optical Coherence/methods ; Retina/diagnostic imaging/pathology ; Spectroscopy, Near-Infrared/methods ; },
abstract = {OBJECTIVE: Near-infrared reflectance (NIR) is a commonly performed noncontact and rapid imaging technique. This paper reviews the clinical applications of NIR for diagnosing and monitoring retinal diseases.<br><br>METHODS: A comprehensive search was conducted across the Pubmed database. A total of 105 articles were finally included in this article. Images were acquired from the authors own clinical experience.<br><br>RESULTS: The article describes the imaging utility of NIR for diagnosing and deomonstrating findings in various conditions. These include retinal vascular diseases, age-related macular degeneration (AMD), vitreoretinal interface pathologies, retinal dystrophies, inflammatory chorioretinopathies, phakomatoses, retinal toxicities, photic injury, choroidal cavitary lesions, choroidal neoplasms, and choroidal Vascular Lesions.<br><br>CONCLUSION: NIR is widely acquired during OCT imaging, and is advantageous at imaging with low illumination levels and through narrow pupils or opaque media. NIR offers valuable information for the diagnosis and follow-up of retinal disease, and is highly recommended to utilize for clinical decision-making in ophthalmology.},
}
@article {pmid39710708,
year = {2025},
author = {Pauleikhoff, D and Yu, S and Bachmeier, I and Armendariz, BG and Bormann, E and Pauleikhoff, L},
title = {Hyperreflective material evolution patterns during long term anti-VEGF therapy in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {4},
pages = {957-964},
pmid = {39710708},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Female ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Visual Acuity ; Follow-Up Studies ; Aged ; *Fluorescein Angiography/methods ; *Ranibizumab/administration &amp; dosage ; Fundus Oculi ; Time Factors ; Aged, 80 and over ; *Bevacizumab/administration &amp; dosage ; *Macula Lutea/pathology ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; },
abstract = {This retrospective, real-life cohort was analyzed to detect the frequency of different HRM evolution patterns and their correlation with MNV types, morphological and functional changes in exudative nAMD under long-term anti-VEGF therapy. We evaluated optical coherence tomography (OCT) volume scans in 143 eyes of 94 nAMD patients (start of anti-VEGF therapy 2009-2018, therapy until the last visit) and recorded the VA at all visits. HRM evolution patterns were differentiated: pattern 1 = no HRM, pattern 2 = subretinal HRM resolved during follow-up, pattern 3 = persistent subretinal HRM with new HRM-boundary remodeling [BR], pattern 4 = persistent subretinal HRM without HRM-BR. Pattern 1 was observed in 58 eyes (40.6%), 33 eyes (23.1%) showed pattern 2, 39 eyes (27.3%) pattern 3 and 13 eyes (9.1%) pattern 4. HRM pattern correlated with type 1-3 MNV (p = 0.02), especially pattern 1 with type 1 MNV and pattern 3 with type 2 MNV. Over time, a change of MNV types could be observed only from type 2 into type 1 MNV (p = 0.0001). Some eyes with HRM pattern 3 changed during follow-up into pattern 4, which was often associated with the presence of macular atrophy (p = 0.0001) and demonstrated a reduced mean VA compared to pattern 1-3 at baseline (p = 0.0001), year 1 (p = 0.0001) and final visit (p = 0.02).In this study, we characterized different HRM evolution patterns in a real-world dataset and demonstrated their associations with MNV transformation during long term anti-VEGF therapy. The HRM patterns may provide prognostic value with morphological and functional implications.},
}
@article {pmid39710334,
year = {2025},
author = {Bishayee, K and Lee, SH and Heo, YJ and Cho, ML and Park, YS},
title = {The unanticipated contribution of Zap70 in retinal degeneration: Implications for microglial inflammatory activation.},
journal = {Progress in neurobiology},
volume = {244},
number = {},
pages = {102706},
doi = {10.1016/j.pneurobio.2024.102706},
pmid = {39710334},
issn = {1873-5118},
mesh = {Animals ; *ZAP-70 Protein-Tyrosine Kinase/metabolism/genetics ; *Microglia/metabolism ; *Retinal Degeneration/metabolism/pathology/immunology ; Mice ; *Inflammation/metabolism/pathology ; Mice, Inbred C57BL ; Retina/metabolism/pathology ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {Inflammation is a major mechanism of photoreceptor cell death in the retina during macular degeneration leading to the blindness. In this study, we investigated the role of the kinase molecule Zap70, which is an inflammatory regulator of the systemic immune system, to elucidate the control mechanism of inflammation in the retina. We observed activated microglial cells migrated and populated the retinal layer following blue LED-induced photoreceptor degeneration and activated microglial cells in the LED-injured retina expressed Zap70, unlike the inactive microglial cells in the normal retina. Visual function was considerably decreased in blue-LED light-exposed mice, and animals with Zap70 mutations were adversely affected. Furthermore, extensive photoreceptor cell death was observed in the SKG mice, bearing a Zap70 mutation that induces autoimmune disease. In the blue-LED light-exposed groups, SKG retinas had significantly higher levels of inflammatory cytokines than those in wild-type mice. Furthermore, regulating Zap70 activity has a significant influence on microglial inflammatory state. We discovered that active microglial cells expressing Zap70 could modify vascular endothelial growth factor A (Vegfa) signaling in primary retinal pigment epithelial (RPE) cells. Our novel study revealed that the production of Zap70 by retinal microglial cells is responsible for inflammatory signals that promote apoptosis in photoreceptor cells. Furthermore, Zap70-positive microglial cells were capable of regulating Vegfa signaling in RPE cells, which matches the hallmark of macular degeneration. Overall, we discovered Zap70's inflammatory activity in the retina, which is necessary for upregulating multiple inflammatory cytokines and cell death. Zap70 represents a novel therapeutic target for treating retinal degeneration.},
}
@article {pmid39710218,
year = {2025},
author = {Pandala, NG and Han, IC and Renze, LJ and Steffen, HJ and Meyering, EE and Stone, EM and Mulfaul, K and Mullins, RF and Tucker, BA},
title = {Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration.},
journal = {Acta biomaterialia},
volume = {194},
number = {},
pages = {98-108},
pmid = {39710218},
issn = {1878-7568},
support = {R01 EY024605/EY/NEI NIH HHS/United States ; R01 EY033331/EY/NEI NIH HHS/United States ; },
mesh = {*Hydrogels/chemistry/pharmacology ; *Macular Degeneration/therapy/pathology/metabolism ; Animals ; *Endothelial Cells/transplantation/metabolism/pathology ; *Choroid/pathology/cytology ; Humans ; Rats ; Cell Survival/drug effects ; Male ; },
abstract = {In retinal diseases such as age-related macular degeneration (AMD) and choroideremia, a key pathophysiologic step is loss of endothelial cells of the choriocapillaris. Repopulation of choroidal vasculature early in the disease process may halt disease progression. Prior studies have shown that injection of donor cells in suspension results in significant cellular efflux and poor cell survival. As such, the goal of this study was to develop a hydrogel system designed to support choroidal endothelial cell transplantation. A library of hydrogels was synthesized using laminin (i.e., LN111, LN121, and LN421), carboxy methyl chitosan, and oxidized dextran via reversible Schiff base chemistry. Each of the developed self-healing hydrogels was readily injectable into the suprachoroidal space, with ideal gelation, mechanical, and degradation properties. While all hydrogels were found to be compatible with choroidal endothelial cell survival in vitro, only LN111 and LN121 gels were well-tolerated in vivo. To determine if hydrogel mediated cell delivery enhances donor cell retention and survival in vivo, iPSC-derived choroidal endothelial cell laden hydrogels were injected into the suprachoroidal space of an immunocompromised choroidal cell injury rat model. Significantly more donor cells were retained and survived in eyes that received cell laden hydrogels versus contralateral hydrogel free controls. Furthermore, donor cells positive for human nuclear antigen were identified in the choroid of hydrogel eyes only. These findings pave the way for future cell replacement studies in large animal models of choroidal cell dropout focused on evaluating functional integration of donor cells within decellularized vascular tubes. STATEMENT OF SIGNIFICANCE: Age related macular degeneration (AMD) is a leading cause of untreatable blindness in the industrial world. A key pathologic step in AMD is loss of the choriocapillaris endothelial cells, which provide vascular support to the overlying retina. Choroidal cell replacement early in disease may prevent retinal cell death and subsequent vision loss. In this study, we present a strategy for repopulating the choriocapillaris using choroidal endothelial cell laden hydrogels. Specifically, we demonstrate the synthesis and characterization of 3 different laminin-based hydrogel systems. LN111 and LN121 hydrogels were found to have excellent biocompatibility both in vitro and in vivo. Hydrogel mediated delivery of iPSC-derived choroidal endothelial cells enhanced donor cell retention and survival, paving the way for functional large animal studies.},
}
@article {pmid39709034,
year = {2025},
author = {Lin, TH and Lin, HY and Tseng, PC},
title = {Enhancing anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy: A meta-analysis.},
journal = {Survey of ophthalmology},
volume = {70},
number = {3},
pages = {380-388},
doi = {10.1016/j.survophthal.2024.12.006},
pmid = {39709034},
issn = {1879-3304},
mesh = {Humans ; *Photochemotherapy/methods ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Polyps/drug therapy/diagnosis ; Photosensitizing Agents/therapeutic use ; Visual Acuity ; Intravitreal Injections ; Verteporfin/therapeutic use ; *Choroid Diseases/drug therapy/diagnosis ; *Choroid/blood supply ; *Choroidal Neovascularization/drug therapy ; Fluorescein Angiography ; Randomized Controlled Trials as Topic ; Polypoidal Choroidal Vasculopathy ; },
abstract = {Anti-vascular endothelial growth factor (anti-VEGF) agents administered as either monotherapy or combination with verteporfin photodynamic therapy (PDT) are the 2 dominant treatment for polypoidal choroidal vasculopathy (PCV); however, controversies remain due to small sample sizes and inconsistency in prognosis from randomized controlled trials (RCTs). In accordance with the PRISMA statement, we investigated the efficacy of PDT plus anti-VEGF combination with anti-VEGF monotherapy. This study was accepted by the International Prospective Register of Systematic Reviews (CRD42023471362). Studies published up to July, 2024, were retrieved from PubMed, Embase, and Cochrane databases. A total of 7 RCTs with 926 eyes were reviewed. In 6 trials, combination therapy showed significantly higher rate of complete polyp regression (risk ratio [RR]: 1.56, 95 % CI: 1.15-2.13, p = 0.005). In 5 trials, combination therapy also significantly reduced the number of anti-VEGF injections (SMD: -0.65, 95 % CI: -0.95 to -0.35, p < 0.0001). For best corrected visual acuity improvement, central retinal thickness reduction, and rate of ocular adverse events, the performance of the 2 modalities were comparable. We conclude that PDT plus anti-VEGF combination therapy constitutes a safe and effective modality and should be considered the first-line treatment for PCV.},
}
@article {pmid39708087,
year = {2025},
author = {Chaudhary, V and Mar, F and Amador, MJ and Chang, A and Gibson, K and Joussen, AM and Kim, JE and Lee, J and Margaron, P and Saffar, I and Wong, D and Wykoff, C and Sadda, S},
title = {Emerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {5},
pages = {1239-1247},
pmid = {39708087},
issn = {1435-702X},
mesh = {Humans ; *Angiopoietin-2/antagonists &amp; inhibitors ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Diseases/drug therapy/metabolism/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; Intravitreal Injections ; Fluorescein Angiography ; Antibodies, Bispecific ; },
abstract = {Anti-vascular endothelial growth factor (VEGF) therapies have transformed the treatment of retinal diseases. However, VEGF signaling is only one component of the complex, multifactorial pathophysiology of retinal diseases, and many patients have residual disease activity despite ongoing anti-VEGF treatment. The angiopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor receptor-2 (Ang/Tie2) signaling pathway is critical to endothelial cell homeostasis, survival, integrity, and vascular stability. Ang-2 can interfere with Ang-1/Tie2 signaling and is increased in several retinal diseases. Lack of Tie2 signaling due to elevated Ang-2 levels drives vascular instability through pericyte dropout, neovascularization, vascular leakage, inflammation, and fibrosis. Although Ang-2 and VEGF can synergistically promote vascular instability and neovascularization, Ang-2 may also mediate vascular instability independently of VEGF. Faricimab is a bispecific antibody designed for intraocular use that inhibits two distinct pathways via Ang-2 and VEGF-A blockade. Clinical biomarkers of vascular instability are important for evaluating disease control and subsequent treatment decisions. These biomarkers include measurement/evaluation with optical coherence tomography (OCT) of intraretinal fluid, subretinal fluid, central subfield thickness, and pigment epithelial detachments (PEDs), and fluorescein angiography imaging of macular leakage and PEDs. Hyperreflective foci (HRF), thought to be representative of activated microglia, indicating an inflammatory microenvironment, and epiretinal membranes (ERMs), a marker for retinal fibrotic proliferation in diabetic macular edema (DME), are both also identified using OCT. Here we summarize data (secondary endpoint and prespecified exploratory analyses as well as post hoc analyses) from six Phase III trials suggest that dual therapy Ang-2/VEGF-A inhibition with faricimab (6 mg) has a greater effect on reducing/resolving biomarkers of vascular instability than aflibercept (2 mg), by both controlling neovascularization and vascular leakage (with resultant resolution of exudation associated with DME, neovascular age-related macular degeneration, and retinal vein occlusion), as well as by targeting inflammation (reduction of HRF in DME) and retinal fibrotic proliferation (reducing the risk of ERMs in eyes with DME). Modulation of both the Ang-2 and VEGF-A pathways with faricimab may therefore provide greater disease control than anti-VEGF monotherapy, potentially leading to extended treatment durability and improved long-term outcomes.},
}
@article {pmid39707561,
year = {2024},
author = {Liu, ZY and Zhang, H and Sun, XL and Liu, JY},
title = {Causal association between metabolites and age-related macular degeneration: a bidirectional two-sample mendelian randomization study.},
journal = {Hereditas},
volume = {161},
number = {1},
pages = {51},
pmid = {39707561},
issn = {1601-5223},
support = {(No. 82125007, 82171073).//the National Natural Science Foundation of China/ ; },
mesh = {*Macular Degeneration/genetics/etiology ; *Mendelian Randomization Analysis ; Humans ; *Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Risk Factors ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly population. Accumulating evidence has revealed the possible association between metabolites and AMD. This study aimed to assess the effect of plasma metabolites on AMD and its two subtypes using a bidirectional two-sample Mendelian randomization approach.<br><br>METHODS: The causality between plasma metabolites and AMD was assessed by a bidirectional two-sample Mendelian randomization (MR) analysis using the genome-wide association studies (GWAS) summary statistics of 1400 genetically determined metabolites (GDMs) and AMD. For this MR analysis, inverse variance weighted (IVW) was used as the primary method, with weighted median, MR-Egger, weighted mode, and simple mode as supplementary methods to examine the causality. MR-Egger intercept, Cochran's Q, and MR-PRESSO test were employed to evaluate possible pleiotropy and heterogeneity.<br><br>RESULTS: The results of IVW showed significant causal associations between 13 GDMs and AMD. 1-stearoyl-GPE (18:0), androstenediol (3&#x3b2;,17&#x3b2;) monosulfate, stearoyl sphingomyelin (d18:1/18:0), xylose, and X-11,850 exhibited a protective effect on AMD, while gulonate and mannonate increased the risk of AMD. 1-stearoyl-GPE (18:0) and X-11,850 exhibited protective effects on dry AMD. DHEAS, 1-stearoyl-GPE (18:0), 5&#x3b1;-androstan-3&#x3b2;,17&#x3b2;-diol disulfate, xylose, androstenediol (3&#x3b2;,17&#x3b2;) monosulfate, and N2-acetyl, N6, N6-dimethyllysine exhibited a protective effect on wet AMD, while succinimide, 16a-hydroxy DHEA 3-sulfate, and X-13,553 increased the risk of wet AMD. Horizontal pleiotropy and heterogeneity did not distort the causal estimates. In the reverse MR analysis, AMD reduced the androstenediol (3&#x3b2;,17&#x3b2;) monosulfate level, and increased the stearoyl sphingomyelin(d18:1/18:0) level.<br><br>CONCLUSION: This study supported the effect of plasma metabolites on AMD, providing novel insights for clinical diagnosis and prevention strategy.},
}
@article {pmid39706380,
year = {2025},
author = {Annuryanti, F and Adhami, M and Abdi, U and Robles, JD and Larrañeta, E and Vora, LK and Raghu Raj Singh, T},
title = {Development of axitinib-loaded polymeric ocular implants for the treatment of posterior ocular diseases.},
journal = {International journal of pharmaceutics},
volume = {669},
number = {},
pages = {125099},
doi = {10.1016/j.ijpharm.2024.125099},
pmid = {39706380},
issn = {1873-3476},
mesh = {*Axitinib/administration &amp; dosage/chemistry ; *Drug Liberation ; Humans ; *Drug Implants ; *Printing, Three-Dimensional ; *Macular Degeneration/drug therapy ; Polymers/chemistry/administration &amp; dosage ; Diabetic Retinopathy/drug therapy ; Delayed-Action Preparations ; Polyesters/chemistry ; Cell Line ; Cell Survival/drug effects ; },
abstract = {Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the primary causes of vision impairment and blindness worldwide. The current treatment for these diseases is an intravitreal injection of anti-VEGF agents, which are costly and require frequent injections. Implants can be used to sustain the release of drugs and minimize side effects. Axitinib (AX) is a potent VEGF receptor inhibitor and a promising candidate for treating posterior ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). A sustained release of AX was successfully achieved from 3D-printed AX-loaded implants fabricated using the well-known 3D printing technique, semi-solid extrusion (SSE). AX at concentrations of 10% w/w and 20% w/w was incorporated within the polycaprolactone (PCL) and Precirol®-based matrix. The fabricated implants were characterized via FTIR spectroscopy, SEM imaging, and thermal analysis. The implants were also evaluated for their drug release and biocompatibility. The AX-loaded implants exhibited thermal stability, and no chemical interactions were found between AX and the matrix components. The release mechanism study of AX revealed that the concentration of drug loading influenced AX release from the implant, with a 10% w/w and 20 %w/w of AX showing first-order and Korsmeyer-Peppas mechanism, respectively. A biocompatibility study using ARPE-19 cells confirmed that AX-loaded implants are nontoxic and safe for ocular use.},
}
@article {pmid39706129,
year = {2025},
author = {Yozgat, Z and Durmus Ece, BS and Isik, MU and Ilguy, S and Sabaner, MC},
title = {Could "Sub-RPE illumination" be a prognostic marker? A prospective dry AMD study.},
journal = {Journal francais d'ophtalmologie},
volume = {48},
number = {3},
pages = {104393},
doi = {10.1016/j.jfo.2024.104393},
pmid = {39706129},
issn = {1773-0597},
mesh = {Humans ; Female ; Male ; Aged ; Tomography, Optical Coherence/methods ; Prognosis ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Disease Progression ; Prospective Studies ; Aged, 80 and over ; *Geographic Atrophy/diagnosis/pathology ; Middle Aged ; *Macular Degeneration/diagnosis/pathology ; Longitudinal Studies ; Lighting/methods ; Visual Acuity ; Biomarkers/analysis ; Follow-Up Studies ; },
abstract = {PURPOSE: To evaluate the natural history of dry age-related macular degeneration (AMD) through advanced retinal pigment epithelium (RPE) analysis and sub-RPE illumination (SRI) data and to elucidate their correlation with disease progression.<br><br>METHODS: A total of 82 patients with dry AMD were included in this longitudinal study. Spectral-domain optical coherence tomography (SD-OCT) was utilized to evaluate central macular thickness (CMT), central retinal thickness (CRT), foveal outer nuclear layer (ONL) thickness, and ellipsoid zone (EZ) integrity. Advanced retinal pigment epithelium (RPE) analysis software was used to obtain area and volume data at 3mm and 5mm circles, as well as sub-RPE illumination (SRI) assessments within 5mm circles.<br><br>RESULTS: After exclusions, the final cohort consisted of 54 eyes of 54 patients (29 female), with a mean age of 74.72&#xb1;8.38years and a mean follow-up period of 13.92&#xb1;1.7months. Both area (mm[2]) and volume (mm[3]) within the 3mm and 5mm circles were significantly increased at the final visit (all P<0.001). From the SRI data, the area within the 5mm circle (mm[2]) was also identified as significantly higher at the final visit (P<0.001). CMT, CRT, and ONL thickness decreased significantly by the final visit (P=0.014, P<0.001, and P<0.001, respectively). Baseline and final LogMAR visual acuity values showed a significant inverse correlation with the distance of SRI from the fovea (P=0.03, r=-0.347 and P=0.04, r=-0.382, respectively). Baseline SRI values were higher in patients with EZ disruption at onset [0.8 (0.1-1.19) vs. 0.0 (0-0.1), P=0.002]. Furthermore, patients with initial EZ disruption had significantly higher final SRI values than those without [1.1 (0.3-2.1) vs. 0.1 (0.1-0.2), P=0.038]. A significant positive correlation was found between the initial SRI area and final LogMAR visual acuity (P<0.001, r=0.645).<br><br>CONCLUSION: Initial SRI area may predict the risk of vision loss over a 12-month follow-up period and could serve as a prognostic marker for progression of dry AMD.},
}
@article {pmid39705870,
year = {2025},
author = {Kılıç, KC and Duruksu, G and Öztürk, A and Rençber, SF and Kılıç, B and Yazır, Y},
title = {Therapeutic potential of adult stem cells-derived mitochondria transfer combined with curcumin administration into ARPE-19 cells in age-related macular degeneration model.},
journal = {Tissue &amp; cell},
volume = {93},
number = {},
pages = {102687},
doi = {10.1016/j.tice.2024.102687},
pmid = {39705870},
issn = {1532-3072},
mesh = {Humans ; *Curcumin/pharmacology ; *Macular Degeneration/therapy/pathology ; *Mitochondria/metabolism/transplantation ; Cell Line ; *Mesenchymal Stem Cells/metabolism/cytology ; Hydrogen Peroxide ; Oxidative Stress/drug effects ; Retinal Pigment Epithelium/pathology ; *Models, Biological ; Cell Survival/drug effects ; Female ; },
abstract = {OBJECTIVE: Mitochondria transfer from human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs-mt) and human endometrium-derived mesenchymal stem cells (hE-MSCs-mt), along with curcumin, were explored as potential treatments for age-related macular degeneration (AMD) caused by mitochondrial inefficiency, using a retinal model to assess impacts of curcumin and hWJ-MSCs-mt or hE-MSCs-mt on AMD.<br><br>METHODS: ARPE-19 cells established an in vitro AMD model. Cells were exposed to 0-50&#x202f;&#x3bc;M curcumin for 24&#x202f;hours to determine optimal concentration by assessing their viability. Immunofluorescence examined SOD1, TNF-&#x3b1;, and TGF-&#x3b2; levels at optimal hydrogen peroxide (H2O2) concentration. &#x3b2;-galactosidase staining and DCFH analysis evaluated H2O2-induced cellular senescence. Immunofluorescence assessed REP65, CRALBP1 (RLBP1), Pink1, and Parkin expression, whereas qRT-PCR analyzed Nrf2, Ire1a, ARMS2, HTRA1, RPE65, RLBP1, NOX4, and TOMM20 expression following co-treatment with curcumin and hWJ-MSCs-mt or hE-MSCs-mt.<br><br>RESULTS: Curcumin improved ARPE-19 cell survival under H2O2-induced oxidative stress by regulating SOD1, TNF-&#x3b1;, TGF-&#x3b2;, DCFH, and MDA levels. hWJ-MSCs-mt transfer increased RLBP1 and Parkin expression, whereas curcumin reduced Parkin expression. hE-MSCs-mt transfer upregulated Parkin, RPE65, Pink1, and RLBP1 expressions, with curcumin enhancing RPE65 expression. hWJ-MSCs-mt and curcumin combined more effectively downregulated expressions of stress-related genes (Nrf2, Ire1&#x3b1;, NOX4) and improved expression of mitochondrial function gene (TOMM20). hE-MSCs-mt transfer with curcumin synergistically enhanced expression of retinal health markers (RPE65, RLBP1) and downregulated expression of damage-associated genes (HTRA1, ARMS2) in AMD models.<br><br>CONCLUSION: Curcumin combined with hWJ-MSCs-mt or hE-MSCs-mt is a potential AMD therapy owing to its anti-inflammatory properties; however, further in vivo and human studies are needed to confirm its efficacy and safety.},
}
@article {pmid39702150,
year = {2024},
author = {Uzun, F},
title = {Clinical characteristics and intravitreal aflibercept outcomes in patients aged 90 years and older with neovascular age-related macular degeneration.},
journal = {BMC geriatrics},
volume = {24},
number = {1},
pages = {1003},
pmid = {39702150},
issn = {1471-2318},
mesh = {Humans ; Male ; Female ; Aged, 80 and over ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Intravitreal Injections ; Retrospective Studies ; *Recombinant Fusion Proteins/administration &amp; dosage ; Treatment Outcome ; Visual Acuity/physiology ; Macular Degeneration/drug therapy ; Wet Macular Degeneration/drug therapy/diagnosis ; Follow-Up Studies ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) stands as the primary cause of visual impairment and blindness among the elderly population. Patients over 90 years comprise a unique demographic that may necessitate particular attention. The aim of this study was to examine the clinical characteristics and treatment outcomes in patients aged 90 years or older diagnosed with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: The medical records of treatment-naive patients aged&#x2009;&#x2265;&#x2009;90 years diagnosed with nAMD have been retrospectively reviewed in our clinic. The complete ophthalmic examination findings of the patients, along with optical coherence tomography and fundus fluorescein angiography records, as well as their adherence to treatment, and reasons for treatment discontinuation were noted. Clinical data following intravitreal injection loading dose and during the 1st and 2nd years of treatment were evaluated.<br><br>RESULTS: The average age of the 45 participants (25 females, 20 males) included in the study was 93.55&#x2009;&#xb1;&#x2009;5.2 years (range; 90-101). The mean best-corrected visual acuity at diagnosis, at the 4th month of treatment, and during the 1st and 2nd years were LogMAR 0.8, 0.5, 0.7 and 1.0, respectively. The most common reasons for missing appointments and completely discontinuing treatment were death and inability to attend appointments due to additional comorbidities.<br><br>CONCLUSION: In the very elderly patient group, nAMD can lead to severe damage in the macula, and a decrease in visual acuity despite treatment is not uncommon. Close monitoring and support for treatment adherence are necessary for this group of patients.},
}
@article {pmid39697885,
year = {2024},
author = {Wang, RY and Zhu, SY and Hu, XY and Sun, L and Zhang, SC and Yang, WH},
title = {Artificial intelligence applications in ophthalmic optical coherence tomography: a 12-year bibliometric analysis.},
journal = {International journal of ophthalmology},
volume = {17},
number = {12},
pages = {2295-2307},
pmid = {39697885},
issn = {2222-3959},
abstract = {AIM: To explore the current application and research frontiers of global ophthalmic optical coherence tomography (OCT) imaging artificial intelligence (AI) research.<br><br>METHODS: The citation data were downloaded from the Web of Science Core Collection database (WoSCC) to evaluate the articles in application of AI in ophthalmic OCT published from January 1, 2012 to December 31, 2023. This information was analyzed using CiteSpace 6.2.R2 Advanced software, and high-impact articles were analyzed.<br><br>RESULTS: In general, 877 articles from 65 countries were studied and analyzed, of which 261 were published by the United States and 252 by China. The centrality of the United States is 0.33, the H index is 38, and the H index of two institutions in England reaches 20. Ophthalmology, computer science, and AI are the main disciplines involved. Hot keywords after 2018 include deep learning (DL), AI, macular degeneration, and automatic segmentation.<br><br>CONCLUSION: The annual number of articles on AI applications in ophthalmic OCT has grown rapidly. The United States holds a prominent position. Institutions like the University of California System and the University of London are spearheading advancements. Initial researches centered on the automatic recognition and diagnosis of ocular diseases leveraging traditional machine learning (ML) technology and OCT images. Nowadays, the imaging process algorithm selection has shifted its focus towards DL. Concurrently, optical coherence tomography angiography (OCTA) and computer-aided diagnosis (CAD) have emerged as key areas of contemporary research.},
}
@article {pmid39697637,
year = {2024},
author = {Hang, A and Ngo, T and Virk, JS and Moussa, K and Moshiri, A and Emami-Naeini, P and Park, SS},
title = {Intravitreal Faricimab for Previously Treated Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3781-3789},
pmid = {39697637},
issn = {1177-5467},
abstract = {PURPOSE: To report our real-world experience using intravitreal faricimab, a novel anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with neovascular age-related macular degeneration (nAMD) previously treated with other anti-VEGF therapy.<br><br>PATIENTS AND METHODS: A retrospective, single-center study of previously treated nAMD eyes treated with faricimab.<br><br>RESULTS: In 88 eyes (73 patients), mean baseline best-corrected visual acuity (BCVA) was 20/63 (range 20/20 to CF) with mean anti-VEGF injection interval of 6.1+2.0&#xa0;weeks. Mean baseline central subfield thickness (CST) was 291+73&#xa0;&#xb5;m. During mean follow-up of 30.1+13.5 (range 7.0 to 50.3) weeks on faricimab, the eyes received an average of 5.1+2.4 injections (range 1 to 11). Mean BCVA remained at 20/63 (p=0.11), but injection interval increased to 7.4+2.6&#xa0;weeks (p<0.001), and CST decreased to 262+63&#xa0;&#xb5;m (p<0.001). Multiple linear regression analysis revealed that higher number of different anti-VEGF drugs used at baseline was associated with a lower decrease in CST on faricimab (p=0.04) while total number of anti-VEGF injections at baseline (p=0.56) and time on faricimab (p=0.68) were not associated. Faricimab was discontinued in 23 eyes (26.1%), including 8 eyes for poor response, 2 eyes for persistent new floaters and 4 eyes for new vision decrease which reversed after stopping faricimab.<br><br>CONCLUSION: In previously treated nAMD eyes, intravitreal faricimab was associated with increased mean treatment interval and decreased CST but no improvement in mean BCVA. The benefit of faricimab on CST reduction may be diminished in eyes previously treated with multiple different types of anti-VEGF therapy.},
}
@article {pmid39695517,
year = {2024},
author = {Zhang, S and Ren, J and Chai, R and Yuan, S and Hao, Y},
title = {Global burden of low vision and blindness due to age-related macular degeneration from 1990 to 2021 and projections for 2050.},
journal = {BMC public health},
volume = {24},
number = {1},
pages = {3510},
pmid = {39695517},
issn = {1471-2458},
support = {71874047//National Natural Science Foundation of China Project/ ; LGF21G030003//Zhejiang Province Public Welfare Technology Application Research Project/ ; 2023ZF034//Zhejiang Province Traditional Chinese Medicine Science and Technology Program Project/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology/complications ; *Blindness/epidemiology/etiology ; *Vision, Low/epidemiology/etiology ; Aged ; *Global Health/statistics &amp; numerical data ; Male ; Female ; *Global Burden of Disease/trends ; Aged, 80 and over ; Middle Aged ; Prevalence ; Forecasting ; Disability-Adjusted Life Years/trends ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness and low vision worldwide. This study examines the global burden and trends in AMD-related low vision and blindness from 1990 to 2021, with projections through 2050.<br><br>METHODS: Data were obtained from the 2021 Global Burden of Disease (GBD 2021) study, covering 204 countries and regions. Key metrics, including the prevalent case numbers, annual disability-adjusted life years (DALYs), age-standardized prevalence rates (ASPR), and age-standardized DALY rates (ASDALYR), specific to low vision and blindness due to AMD, were calculated per 100,000 population. Trend analysis used the estimated annual percentage change (EAPC) method, and K-means clustering identified regions with similar burdens and trends. Autoregressive Integrated Moving Average(ARIMA) and Exponential Smoothing(ES) models provided future projections.<br><br>RESULTS: Globally, the total number of prevalent cases and DALYs has substantially increased. The number of prevalent cases of low vision and blindness due to AMD increased from 3,640,180 (95% UI: 3,037,098&#x2009;-&#x2009;4,353,902) in 1990 to 8,057,521 (95% UI: 6,705,284-9,823,238) in 2021. DALYs increased from 302,902 (95% UI: 206,475&#x2009;-&#x2009;421,952) in 1990 to 578,020 (95% UI: 401,241-797,570) in 2021. From 1990 to 2021, both the ASPR and ASDALYR for AMD-related low vision and blindness showed a downward trend. The ASPR was 94 (95% UI: 78.32-114.42) per 100,000 population, with an EAPC of -0.26 (95% CI: -0.31 to -0.22), and the ASDALYR was 6.78 (95% UI: 4.7-9.32) per 100,000 population, with an EAPC of -0.94 (95% CI: -1.01 to -0.88). The disease burden of AMD-related low vision and blindness increases with age, and the burden for female patients is slightly higher than for males. Regional stratification by the Socio-Demographic Index (SDI) shows that the burden of AMD-related low vision and blindness in areas with low SDI is higher than in areas with high SDI. From 1990 to 2021, notable increases in ASPR and ASDALYR were observed mainly in the southern and central regions of sub-Saharan Africa. Moreover, the increases in prevalence and DALYs vary by region, country, and level of socioeconomic development. The ARIMA model predicts that by 2050, the number of prevalent cases of low vision and blindness due to AMD will reach 13,880,610(95% CI: 9,805,575-17,955,645), and the DALYs will be 764,731(95% CI: 683,535-845,926). The ES model predicts that by 2050, the number of prevalent cases of AMD-related low vision and blindness will reach 9,323,124(95% CI: 5,222,474-13,423,774), and the DALYs will be 641,451 (95% CI: 383,588-899,318).<br><br>CONCLUSION: This study indicates that between 1990 and 2021, the global prevalent cases and DALYs caused by AMD-related low vision and blindness have increased over the past three decades, correlating with factors such as age, gender, socioeconomic status, and geographical location. Predictive models indicate that as the population ages, the number of patients with low vision and blindness due to AMD, along with associated DALYs, will continue to rise. By 2050, it is expected that over 9&#xa0;million people worldwide will be affected by AMD-related vision loss, with women being particularly impacted. These findings can provide data support for public health planning, resource allocation, and the formulation of medical policies, ensuring an effective response to the challenges posed by the future increase in AMD-related low vision and blindness.},
}
@article {pmid39694681,
year = {2025},
author = {Panda, P and Mohanty, S and Gouda, SR and Mohapatra, R},
title = {Advances in nanomedicine for retinal drug delivery: overcoming barriers and enhancing therapeutic outcomes.},
journal = {Journal of drug targeting},
volume = {33},
number = {5},
pages = {587-611},
doi = {10.1080/1061186X.2024.2443144},
pmid = {39694681},
issn = {1029-2330},
mesh = {Humans ; *Nanomedicine/methods ; *Drug Delivery Systems/methods ; Animals ; *Retina/metabolism/drug effects ; Nanoparticles/chemistry ; *Retinal Diseases/drug therapy ; Diabetic Retinopathy/drug therapy ; },
abstract = {Nanomedicine offers a promising avenue for improving retinal drug delivery, effectively addressing challenges associated with ocular diseases like age-related macular degeneration and diabetic retinopathy. Nanoparticles, with their submicron size and customisable surface properties, enable enhanced permeability and retention within retinal tissues, supporting sustained drug release and minimising systemic side effects. Nanostructured scaffolds further provide a supportive environment for retinal cell growth and tissue regeneration, crucial for treating degenerative conditions. Additionally, advanced nanodevices facilitate real-time monitoring and controlled drug release, marking significant progress in retinal therapy. This study reviews recent advancements in nanomedicine for retinal drug delivery, critically analysing design innovations, therapeutic benefits, and limitations of these systems. By advancing nanotechnology integration in ocular therapies, this field holds strong potential for overcoming current barriers, ultimately improving patient outcomes and quality of life.},
}
@article {pmid39694604,
year = {2025},
author = {Pu, J and Zhuang, X and Li, M and Hao, X and He, G and Su, Y and Gan, Y and Zhang, X and Ji, Y and Mi, L and Zhang, Y and Yang, R and Chen, X and Wen, F},
title = {Prognostic value of macular neovascularisation characteristics for photoreceptor integrity in nAMD: a prospective observational study.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {6},
pages = {689-696},
doi = {10.1136/bjo-2024-326319},
pmid = {39694604},
issn = {1468-2079},
mesh = {Humans ; Male ; Female ; Prospective Studies ; Tomography, Optical Coherence/methods ; Aged ; Prognosis ; Fluorescein Angiography/methods ; Visual Acuity/physiology ; Follow-Up Studies ; *Photoreceptor Cells, Vertebrate/pathology ; *Wet Macular Degeneration/diagnosis/physiopathology/drug therapy ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Retinal Vessels/pathology ; Fundus Oculi ; },
abstract = {PURPOSE: To explore the relationship between characteristics of macular neovascularisation (MNV) and photoreceptor integrity in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective study enrolled treatment-na&#xef;ve nAMD eyes and conducted a 3-month follow-up. 16 quantitative MNV features were evaluated using optical coherence tomography angiography, and the impaired areas of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL) were obtained using optical coherence tomography. Correlation and regression analyses assessed the relationships between MNV features and photoreceptor integrity.<br><br>RESULTS: 110 nAMD eyes from 110 patients (73.64% men) were included. Baseline MNV characteristics, including MNV perimeter, maxFeret, minFeret, vessel area, total vessel length, total number of junctions and endpoints, and mean E lacunarity, were positively correlated with photoreceptor damage areas (r ranging from 0.227 to 0.558, p<0.05 for all). Meanwhile, vessel density negatively correlated with photoreceptor damage (r=-0.468 for EZ, -0.394 for ELM and -0.538 for ONL, all p<0.05). After the loading phase, the EZ prognosis was independently associated with baseline MNV minFeret (Std &#x3b2;=0.362, p=0.011) and mean E lacunarity (Std &#x3b2;=0.130, p=0.041). The prognosis for ELM was independently linked to baseline MNV minFeret (Std &#x3b2;=0.373, p=0.014), while no significant factors were found to influence ONL prognosis (p>0.05 for all).<br><br>CONCLUSION: A strong correlation was observed between MNV features and photoreceptor integrity, with larger and more complex vascular networks associated with greater photoreceptor damage.},
}
@article {pmid39694277,
year = {2025},
author = {Steinle, NC and McCullough, AJ and Silva, FQ and Du, W and Moini, H and Singh, RP},
title = {Impact of Duration of Exposure to Intraretinal Fluid on Visual Outcomes in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {7},
pages = {618-624},
doi = {10.1016/j.oret.2024.12.018},
pmid = {39694277},
issn = {2468-6530},
mesh = {Humans ; *Visual Acuity ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Male ; Female ; Angiogenesis Inhibitors/administration &amp; dosage ; *Quality of Life ; *Ranibizumab/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Aged ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Subretinal Fluid/drug effects ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Treatment Outcome ; Time Factors ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; },
abstract = {OBJECTIVE: To evaluate the impact of total duration of intraretinal fluid (IRF) exposure on visual acuity and vision-related quality of life in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: A post hoc analysis of integrated data from the VIEW 1 and VIEW 2 trials.<br><br>PARTICIPANTS: Patients with nAMD.<br><br>METHODS: Patients receiving intravitreal ranibizumab 0.5 mg every 4 weeks (Rq4) or intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4) or 2 mg every 8 weeks (2q8) were evaluated. Data were pooled across treatment groups, and the duration of IRF exposure was assessed by quartiles (first quartile [Q1]: &#x2264;2 weeks; second quartile [Q2]: 3 to &#x2264;8 weeks; third quartile [Q3]: 9 to &#x2264;18 weeks; fourth quartile [Q4]: >18 weeks). Changes from baseline in visual acuity and vision-related quality of life were evaluated by quartiles of duration of IRF exposure in the pooled treatment group and each treatment group.<br><br>MAIN OUTCOME MEASURES: Mean changes from baseline in best-corrected visual acuity (BCVA) and improvement in vision-related quality of life as assessed via National Eye Institute Visual Function Questionnaire-25 (VFQ-25) composite and subscale scores at week 52.<br><br>RESULTS: A total of 1804 patients were evaluated. In the pooled analysis, mean BCVA gains from baseline at week 52 for Q1, Q2, Q3, and Q4 were +10.9, +10.1, +9.4, and +6.6 letters, respectively (Least squares mean difference Q4-Q1 [95% confidence interval]; -4.3 [-6.1, -2.5]). Mean changes from baseline to week 52 in VFQ-25 composite score for Q1, Q2, Q3, and Q4 were +5.9, +6.6, +6.1, and +4.0 points, respectively (-1.9 [-3.6, -0.2]). A similar trend was observed across VFQ-25 subscales, with patients in Q4 generally experiencing less improvement versus Q1. When BCVA gains were assessed by quartiles of duration of IRF exposure within each treatment group, mean BCVA gains for Q1, Q2, Q3, and Q4 were +11.0, +11.1, +9.3, and +5.8 letters for Rq4 (nominal P < 0.05; Q4 vs. Q1); +10.7, +9.7, +9.2, and +7.7 letters for IAI 2q4; and +11.3, +11.2, +8.6, and +6.3 letters for IAI 2q8 (nominal P < 0.05; Q4 vs. Q1), respectively.<br><br>CONCLUSIONS: Increasing duration of IRF exposure was associated with lower visual gains and less improvement in vision-related quality of life in patients with nAMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39694270,
year = {2025},
author = {Chowdhury, JM and Chacin Ruiz, EA and Ohr, MP and Swindle-Reilly, KE and Ford Versypt, AN},
title = {Computer modeling of bevacizumab drug distribution after intravitreal injection in rabbit and human eyes.},
journal = {Journal of pharmaceutical sciences},
volume = {114},
number = {2},
pages = {1164-1174},
pmid = {39694270},
issn = {1520-6017},
support = {R01 EB032870/EB/NIBIB NIH HHS/United States ; R35 GM133763/GM/NIGMS NIH HHS/United States ; },
mesh = {Rabbits ; *Bevacizumab/pharmacokinetics/administration &amp; dosage ; Intravitreal Injections ; Animals ; Humans ; *Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage ; *Vitreous Body/metabolism ; Computer Simulation ; Aqueous Humor/metabolism ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Macular Degeneration/drug therapy/metabolism ; *Models, Biological ; Tissue Distribution ; },
abstract = {Age-related macular degeneration (AMD) is a progressive eye disease that causes loss of central vision and has no cure. Wet AMD is the late neovascular form treated with vascular endothelial growth factor (VEGF) inhibitors. VEGF is the critical driver of wet AMD. One common off-label anti-VEGF drug used in AMD treatment is bevacizumab. Experimental efforts have been made to investigate the pharmacokinetic (PK) behavior of bevacizumab in vitreous and aqueous humor. Still, the quantitative effect of elimination routes and drug concentration in the macula are not well understood. In this work, we developed two spatial models representing rabbit and human vitreous to better understand the PK behavior of bevacizumab. This study explores different cases of drug elimination and the effects of injection location on drug concentration profiles. The models are validated by comparing them with experimental data. Our results suggest that anterior elimination is dominant for bevacizumab clearance from rabbit vitreous, whereas both anterior and posterior elimination have similar importance in drug clearance from the human vitreous. Furthermore, results indicate that drug injections closer to the posterior segment of the vitreous help maintain relevant drug concentrations for longer, improving bevacizumab duration of action in the vitreous. The rabbit and human models predict bevacizumab concentration in the vitreous and fovea, enhancing knowledge and understanding of wet AMD treatment.},
}
@article {pmid39693344,
year = {2024},
author = {Hata, M and Hata, M and Dejda, A and Pilon, F and Diaz-Marin, R and Fournier, F and Joyal, JS and Cagnone, G and Ochi, Y and Crespo-Garcia, S and Wilson, AM and Sapieha, P},
title = {Corticosteroids reduce pathological angiogenesis yet compromise reparative vascular remodeling in a model of retinopathy.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {52},
pages = {e2411640121},
pmid = {39693344},
issn = {1091-6490},
support = {353770//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; M2022015I//BrightFocus Foundation (BFF)/ ; },
mesh = {Animals ; Mice ; *Disease Models, Animal ; *Vascular Remodeling/drug effects ; Dexamethasone/pharmacology ; Retinal Neovascularization/drug therapy/metabolism/pathology ; Microglia/drug effects/metabolism/pathology ; Neovascularization, Pathologic/drug therapy/metabolism ; CX3C Chemokine Receptor 1/metabolism/genetics ; Myeloid Cells/drug effects/metabolism ; Retinal Vessels/drug effects/pathology/metabolism ; Mice, Inbred C57BL ; Retina/drug effects/pathology/metabolism ; Adrenal Cortex Hormones/pharmacology/therapeutic use ; Muramidase/metabolism ; Inflammation/drug therapy/pathology ; Oxygen/metabolism ; Immunity, Innate/drug effects ; },
abstract = {Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system, this is observed through a predominantly innate immune response in retinal vascular diseases such as age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Here, we set out to elucidate the dynamics of the immune response during progression and regression of pathological neovascularization in retinopathy. In a mouse model of oxygen-induced retinopathy, we report that dexamethasone, a broad-spectrum corticosteroid, suppresses initial formation of pathological preretinal neovascularization in early stages of disease, yet blunts reparative inflammation by impairing distinct myeloid cell populations, and hence reduces beneficial vascular remodeling in later stages of disease. Using genetic depletion of distinct components of the innate immune response, we demonstrate that CX3C chemokine receptor 1-expressing microglia contribute to angiogenesis. Conversely, myeloid cells expressing lysozyme 2 are recruited to sites of damaged blood vessels and pathological neovascularization where they partake in a reparative process that ultimately restores circulatory homeostasis to the retina. Hence, the Janus-faced properties of anti-inflammatory drugs should be considered, particularly in stages associated with persistent neovascularization.},
}
@article {pmid39693084,
year = {2024},
author = {Seddon, JM and De, D and Grunenkovaite, L and Ferrara, D},
title = {Clinical and Imaging Characteristics of PRPH2 Retinopathies in a Longitudinal Cohort and Diagnostic Implications.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {31},
pmid = {39693084},
issn = {1552-5783},
support = {R01 EY011309/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; Adult ; *Peripherins/genetics ; *Tomography, Optical Coherence/methods ; Aged ; Pedigree ; Young Adult ; Adolescent ; Visual Acuity/physiology ; Follow-Up Studies ; Retinal Dystrophies/genetics/diagnosis ; Fluorescein Angiography/methods ; Genetic Association Studies ; Mutation ; Child ; Multimodal Imaging ; DNA Mutational Analysis ; DNA/genetics ; Longitudinal Studies ; },
abstract = {PURPOSE: The purpose of this study was to define genotypic-phenotypic correlations related to PRPH2-associated retinopathies in an observational longitudinal cohort and to improve diagnostic accuracy.<br><br>METHODS: Individuals with PRPH2 variants were identified by genetic sequencing of 263 individuals (including 59 families). Ocular examinations with multimodal imaging were evaluated.<br><br>RESULTS: Two pathogenic/likely pathogenic PRPH2 variants were identified in 22 individuals with retinopathies, low genetic susceptibility to age-related macular degeneration (AMD) and younger age of onset. The mean follow-up was 14 years. One family and 4 independent cases (n = 7) were heterozygous for the variant rs121918563 L185P (p.Leu185Pro). The individuals developed retinopathy compatible with autosomal dominant pattern dystrophy (PD), including adult-onset vitelliform macular dystrophy and butterfly macular dystrophy in their fourth to fifth decades of life, evolving to retinal pigment epithelial (RPE) irregularities and central macular atrophy 20&#xa0;years later. Two families and an independent case (n = 15) had the rs281865373 splice-site variant c.828+3A>T (IVS2+3A>T) presenting as retinal flecks consistent with adult-onset fundus flavimaculatus with macular dystrophy and diffuse RPE atrophy consistent with central areolar chorioretinal dystrophy (CACD) in the fifth decade of life progressing to extensive atrophy in the sixth to eighth decades. The L185P variant was associated with better visual acuity (VA) during follow-up versus c.828+3A>T variant. Some individuals were initially misdiagnosed with geographic atrophy secondary to AMD.<br><br>CONCLUSIONS: Individuals with the L185P variant had less severe disease with clinical manifestation typical of PD and better VA. More advanced disease with CACD and worse VA were associated with the c.828+3A>T variant. Results contribute to knowledge about genotypic-phenotypic associations of PRPH2 retinopathies and inform clinical and therapeutic end points.},
}
@article {pmid39692064,
year = {2025},
author = {Egger, D and Doll, B and Gonzalez, C and Ahmadzai, P and Heger, KA and Kreid, B and Montuoro, A and Link, J and Yamaguchi, TC and Esmaeelpour, M and Waldstein, SM},
title = {Photoreceptor-RPE loss ratio and fundus autofluorescence patterns as predictive factors for lesion progression in geographic atrophy.},
journal = {Acta ophthalmologica},
volume = {103},
number = {4},
pages = {e204-e212},
doi = {10.1111/aos.17431},
pmid = {39692064},
issn = {1755-3768},
support = {//Boehringer Ingelheim/ ; },
mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Retinal Pigment Epithelium/pathology ; Retrospective Studies ; Male ; *Tomography, Optical Coherence/methods ; Disease Progression ; *Fluorescein Angiography/methods ; Female ; Aged ; Fundus Oculi ; Follow-Up Studies ; Middle Aged ; *Photoreceptor Cells, Vertebrate/pathology ; Aged, 80 and over ; Visual Acuity ; },
abstract = {PURPOSE: To assess the impact of the ratio between photoreceptor (PR) loss and retinal pigment epithelium (RPE) loss on the progression of geographic atrophy (GA) and to explore correlations between abnormal fundus autofluorescence (FAF) patterns and the PR-RPE loss ratio.<br><br>DESIGN: Single-centre, retrospective case series.<br><br>METHODS: Multimodal images from 87 treatment-na&#xef;ve patients with GA and a follow-up of 6-24&#x2009;months were included. Geographic atrophy areas on FAF images and areas of PR-RPE loss on optical coherence tomography images at baseline were manually annotated, and FAF patterns were classified. The impact of these biomarkers on GA progression through month 24 as measured on FAF was evaluated using random slope and intercept models and Spearman correlation coefficients (&#x3c1;).<br><br>RESULTS: Mean square-root GA growth rate was 0.27&#x2009;&#xb1;&#x2009;0.28&#x2009;mm per year. Mean PR-RPE loss ratio at baseline was 2.16&#x2009;&#xb1;&#x2009;1.75. Fundus autofluorescence patterns "diffuse" and "diffuse trickling" showed higher PR-RPE loss ratios at baseline and contributed statistically significantly to the slope of GA progression (p&#x2009;=&#x2009;0.01 and p&#x2009;=&#x2009;0.0019). Baseline GA lesion size was negatively correlated to PR-RPE loss ratios at baseline (&#x3c1;&#x2009;=&#x2009;-0.47, p&#x2009;<&#x2009;0.0001). Overall, GA growth was higher in patients with higher PR-RPE loss ratios at baseline (&#x3c1;&#x2009;=&#x2009;0.35, p&#x2009;=&#x2009;0.0011), and the ratio's contribution to the slope of GA progression was statistically significant (p&#x2009;=&#x2009;0.0001).<br><br>CONCLUSION: Eyes with higher PR-RPE loss ratios were more likely to exhibit FAF patterns "diffuse" and "diffuse trickling" and showed higher GA progression rates. Baseline characteristics derived from FAF and OCT images may thus offer information on lesion progression.},
}
@article {pmid39692058,
year = {2025},
author = {Le, HM and Querques, G and Guenoun, S and El Ghazi, D and Haddad, WM and Mouallem, A and Semoun, O and Souied, EH},
title = {Acute intra ocular inflammation following intravitreal injections of faricimab: A multicentric case series.},
journal = {European journal of ophthalmology},
volume = {35},
number = {4},
pages = {1358-1365},
doi = {10.1177/11206721241306225},
pmid = {39692058},
issn = {1724-6016},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Acute Disease ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Fluorescein Angiography ; Intravitreal Injections/adverse effects ; Retinal Vein Occlusion/drug therapy ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity ; *Eye Diseases/chemically induced ; Antibodies, Bispecific ; },
abstract = {PurposeTo report 8 cases of acute intra ocular inflammation (IOI) following intravitreal injections (IVI) of faricimab in patients with age related macular degeneration (AMD), retinal vein occlusion (RVO) and macular neovascularization associated with chronic central serous retinopathy (CSR).MethodsThis is a multicentric retrospective observational case-series. Cases of acute IOI that occurred in 5 different institutions in France and Italy between November 2023 and June 2024 were reported.Results8 eyes of 8 patients presented with acute IOI following IVI of faricimab. Best corrected visual acuity (BCVA) at the time of the IOI event varied between counting fingers and 20/25. 6 patients had neovascular AMD, 1 patient had a macular edema secondary to central RVO and 1 patient had a macular neovascularization associated with chronic CSR. Mean delay between the last IVI of faricimab and the assessment of the IOI event was 10.0 days. Presentation of IOI varied among patients. 6 patients presented with vitritis with varying severity. One of them had an associated papillitis. One patient presented with an anterior uveitis without vitritis. Corticosteroids were used in 5 cases. 2 cases resolved spontaneously. Surgery was needed in 1 case. These 8 cases of IOI occurred out of a total of 1923 IVI of faricimab performed with an estimated frequency of 0.41%.ConclusionAcute IOI may happen after IVI of faricimab. Severity of inflammation varies and treatment should be adjusted according to the clinical presentation.},
}
@article {pmid39691308,
year = {2024},
author = {Bakri, SJ and Brinkmann, CK and Mulvey, A and Steinberg, K and Katz, R and Vatsyayan, P and Sarda, SP and Holekamp, NM},
title = {Characterizing Patient Perceptions of Living with Geographic Atrophy: The Global Geographic Atrophy Insights Survey.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3725-3737},
pmid = {39691308},
issn = {1177-5467},
abstract = {BACKGROUND: Geographic atrophy (GA) is an advanced form of age-related macular degeneration leading to irreversible vision loss and negative impacts on quality of life.<br><br>METHODS: To assess the experiences of living with GA, the Geographic Atrophy Insights Survey (GAINS) was conducted between October 12, 2021, and December 10, 2021, captured the responses of individuals &#x2265;60 years with a self-reported GA diagnosis residing in the United States, Canada, Australia, and six European countries. Survey questions focused on the perceptions of individuals living with GA and covered six themes: speed of disease progression, effect on independence, impact on quality of life, emotional toll of GA, misconceptions and need for further education about GA, and clinician interactions. An exploratory comparison between participants with unilateral and bilateral GA was conducted.<br><br>RESULTS: The survey included 203 individuals with a mean age of 70 years; 42% had bilateral GA. Most respondents (77%) agreed ("strongly" or "somewhat agreed") that GA impacted their vision faster than expected, and 68% agreed that it is hard to enjoy life fully the way they did before GA diagnosis. Regarding comparisons between individuals with bilateral and unilateral GA, both groups reported similar "major" or "moderate" negative impacts on their ability to drive (73% vs 75%, respectively), followed by the ability to read (66% vs 71%), and ability to travel as much as they would prefer (62% vs 62%). Among participants, 49% and 56% of respondents with bilateral and unilateral GA, respectively, reported major/moderate negative impacts on self-confidence and 40% of both cohorts reported major/moderate negative impacts on mental health.<br><br>CONCLUSION: Our survey provides further insight on the burden experienced by individuals living with GA. We find similar responses between unilateral and bilateral GA groups, highlighting the impact GA may have on an individual's quality of life even when only one eye is affected.},
}
@article {pmid39690869,
year = {2024},
author = {Liu, H and Yan, W and Luo, D and Li, J and Yan, D},
title = {A real‑world pharmacovigilance study of raloxifene based on the FDA adverse event reporting system (FAERS).},
journal = {Expert opinion on drug safety},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/14740338.2024.2443960},
pmid = {39690869},
issn = {1744-764X},
abstract = {BACKGROUND: Raloxifene was approved for the treatment of postmenopausal osteoporosis; however, its safety profile remains inadequately understood. This study aimed to evaluate the safety signals associated with raloxifene.<br><br>RESEARCH DESIGN AND METHODS: Adverse events (AEs) related to raloxifene, spanning from the first quarter of 2004 to the fourth quarter of 2023, were extracted from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was conducted using several methods, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM).<br><br>RESULTS: The analysis yielded 7 229 reports related to raloxifene across 19 277 AEs. A total of 217 significantly disproportionate signals were identified, including muscle spasms and hot flashes. Notably, the study also uncovered novel AEs, including eye conditions like cataracts and macular degeneration, as well as gynecological issues like uterine polyps and hemorrhage. Additionally, the analysis confirmed that pulmonary embolism and deep vein thrombosis were the two most prevalent thromboembolic AEs.<br><br>CONCLUSION: Our study reaffirmed some existing safety information regarding raloxifene while also unveiling novel risk signals. The findings provided crucial insights to enhance the rational use of the drug and inform safety regulatory strategies.},
}
@article {pmid39689291,
year = {2025},
author = {Lee, CH and Bae, K and Yoon, CK and Park, UC and Park, KH and Lee, EK},
title = {CLINICAL COURSE AND PROGNOSTIC FACTORS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH SUBRETINAL FLUID.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {4},
pages = {714-723},
doi = {10.1097/IAE.0000000000004368},
pmid = {39689291},
issn = {1539-2864},
support = {NRF-2021R1F1A1045417//National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (Information and Communication Technology)/ ; 0620215,600//Bayer Korea/ ; },
mesh = {Humans ; *Subretinal Fluid/diagnostic imaging ; Male ; Female ; Tomography, Optical Coherence/methods ; Aged ; Prognosis ; Fluorescein Angiography/methods ; Retrospective Studies ; Aged, 80 and over ; Visual Acuity ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; *Macular Degeneration/diagnosis/complications ; Disease Progression ; Middle Aged ; *Retinal Detachment/diagnosis ; Fundus Oculi ; },
abstract = {PURPOSE: To investigate the clinical course and prognostic factors of age-related macular degeneration without macular neovascularization (MNV) in patients presenting with pigment epithelial detachment (PED) and the associated subretinal fluid (SRF).<br><br>METHODS: Morphological characteristics of spectral-domain optical coherence tomography images were analyzed to determine anatomic outcomes. Factors associated with the progression to late AMD, defined as complete retinal pigment epithelium and outer retinal atrophy (cRORA) or MNV, were investigated.<br><br>RESULTS: Fifty eyes of 41 patients were included in this study. The most common SRF location was the angle of the PED (56%), and there was a significant decrease in SRF thickness and PED height and width over the follow-up period. Eleven (22%) eyes developed cRORA, and seven (14%) eyes developed MNV during a mean period of 52.1 months. Multivariate analysis revealed that hyperreflective foci and MNV in the fellow eye were associated with the development of cRORA, and higher PED height was a significant factor associated with the development of MNV.<br><br>CONCLUSION: In patients with AMD, SRF can be accompanied by PED in the absence of MNV. Notably, patients with this characteristic entity can progress to late AMD, including cRORA and MNV, in a significant proportion of cases.},
}
@article {pmid39688851,
year = {2024},
author = {Duncan, JL and Bowman, A and Laster, A and Gelfman, C and Birch, DG and Boye, SE and Daiger, SP and Del Priore, L and Zack, DJ and Handa, JT and , },
title = {Inherited Retinal Degenerations and Non-Neovascular Age-Related Macular Degeneration: Progress and Unmet Needs.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {12},
pages = {28},
pmid = {39688851},
issn = {2164-2591},
mesh = {Humans ; *Macular Degeneration/genetics/therapy/pathology ; *Retinal Degeneration/genetics/therapy ; Genetic Therapy/methods ; Geographic Atrophy/genetics/therapy ; cis-trans-Isomerases/genetics ; },
abstract = {Inherited retinal degeneration (IRD) disease and age-related macular degeneration (AMD) are leading causes of irreversible vision loss and blindness. Although significant progress has advanced the field in the past 5 years, significant challenges remain. The current article reviews the accomplishments and research advances that have fueled the development of treatments for patients with IRD and AMD, including the first approved gene-augmentation treatment for RPE65-related retinal degeneration and complement inhibition therapies to slow progression of geographic atrophy (GA) in AMD. The article outlines opportunities to address gaps and unmet needs that should lead to additional progress toward the development of treatments for patients with IRDs and non-neovascular AMD in the future.},
}
@article {pmid39688575,
year = {2025},
author = {Agadagba, SK and Yau, SY and Liang, Y and Dalton, K and Thompson, B},
title = {Bidirectional causality of physical exercise in retinal neuroprotection.},
journal = {Neural regeneration research},
volume = {20},
number = {12},
pages = {3400-3415},
pmid = {39688575},
issn = {1673-5374},
abstract = {Physical exercise is recognized as an effective intervention to improve mood, physical performance, and general well-being. It achieves these benefits through cellular and molecular mechanisms that promote the release of neuroprotective factors. Interestingly, reduced levels of physical exercise have been implicated in several central nervous system diseases, including ocular disorders. Emerging evidence has suggested that physical exercise levels are significantly lower in individuals with ocular diseases such as glaucoma, age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. Physical exercise may have a neuroprotective effect on the retina. Therefore, the association between reduced physical exercise and ocular diseases may involve a bidirectional causal relationship whereby visual impairment leads to reduced physical exercise and decreased exercise exacerbates the development of ocular disease. In this review, we summarize the evidence linking physical exercise to eye disease and identify potential mediators of physical exercise-induced retinal neuroprotection. Finally, we discuss future directions for preclinical and clinical research in exercise and eye health.},
}
@article {pmid39685491,
year = {2024},
author = {Korb, CA and Gerstenberger, E and Lorenz, K and Bell, K and Beck, A and Scheller, Y and Beutgen, VM and Wolters, D and Grus, FH},
title = {Correlation of Functional and Structural Outcomes with Serum Antibody Profiles in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab and Healthy Subjects: A Prospective, Controlled Monocenter Trial.},
journal = {Journal of clinical medicine},
volume = {13},
number = {23},
pages = {},
pmid = {39685491},
issn = {2077-0383},
support = {n.a.//Novartis Pharma GmbH, N&#xfc;rnberg, Germany/ ; },
abstract = {Background: Age-related macular degeneration (AMD) is a multifactorial disorder, and there is growing evidence of immunological involvement in its pathogenesis. To address this, we aimed to identify biomarker candidates related to retinal antigens in patients with neovascular AMD treated with ranibizumab and healthy subjects. Materials and Methods: This study was designed as a prospective, open, parallel-group, interventional, single-center phase IV trial. Fifty subjects with neovascular AMD and twenty healthy volunteers were enrolled. The primary objective was to assess the efficacy of intravitreally (IVT) administered ranibizumab in terms of the change in best-corrected visual acuity in subjects with all subtypes of neovascular AMD and in a subgroup of pretreated AMD subjects. A secondary objective was to assess the efficacy of the same in terms of the change in central retinal thickness (CRT) in the same subjects. Another secondary objective was to identify antibodies against retinal antigens in patients with neovascular AMD treated with ranibizumab and healthy subjects. The last secondary objective was to correlate functional and structural parameters with the identified biomarker candidates to differentiate between initial and deferred responders to IVT administered ranibizumab. Serum was analyzed using customized antigen microarrays containing 58 antigens. Results: After 12 weeks of ranibizumab treatment, treated patients gained 4.02 letters on average. The central retinal thickness (CRT) measured in the complete AMD study population was significantly (p < 0.001) decreased at Week 24 compared to the baseline measurement, and the mean CRT dropped from 393.4 to 296.8 µm. A significant increase in the following autoantibodies was detected between the control group and AMD group at Week 24, as well as in the AMD group between baseline and Week 24: antibodies targeting the proteins serotransferrin, opioid growth factor receptor, 60 kDa chaperonin 2, neurotrophin-4, dermcidin, clusterin and vascular endothelial growth factor. Conclusions: The present trial was able to confirm the efficacy of ranibizumab treatment in neovascular AMD, and treatment-naïve patients benefitted the most. Up- and downregulations of antibodies were observed over the course of treatment with ranibizumab. Some antibodies seemed to have a fair correlation with the classification of initial and deferred responders.},
}
@article {pmid39684764,
year = {2024},
author = {Marchesi, N and Capierri, M and Pascale, A and Barbieri, A},
title = {Different Therapeutic Approaches for Dry and Wet AMD.},
journal = {International journal of molecular sciences},
volume = {25},
number = {23},
pages = {},
pmid = {39684764},
issn = {1422-0067},
support = {PRIN2020FR7TCL//MIUR/ ; },
mesh = {Humans ; *Wet Macular Degeneration/drug therapy/therapy ; Vascular Endothelial Growth Factor A/metabolism ; Macular Degeneration/therapy ; Angiogenesis Inhibitors/therapeutic use ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is the most common cause of irreversible loss of central vision in elderly subjects, affecting men and women equally. It is a degenerative pathology that causes progressive damage to the macula, the central and most vital part of the retina. There are two forms of AMD depending on how the macula is damaged, dry AMD and wet or neovascular AMD. Dry AMD is the most common form; waste materials accumulate under the retina as old cells die, not being replaced. Wet AMD is less common, but can lead to vision loss much more quickly. Wet AMD is characterized by new abnormal blood vessels developing under the macula, where they do not normally grow. This frequently occurs in patients who already have dry AMD, as new blood vessels are developed to try to solve the problem. It is not known what causes AMD to develop; however, certain risk factors (i.e., age, smoking, genetic factors) can increase the risk of developing AMD. There are currently no treatments for dry AMD. There is evidence that not smoking, exercising regularly, eating nutritious food, and taking certain supplements can reduce the risk of acquiring AMD or slow its development. The main treatment for wet AMD is inhibitors of VEGF (vascular endothelial growth factor), a protein that stimulates the growth of new blood vessels. VEGF inhibitors can stop the growth of new blood vessels, preventing further damage to the macula and vision loss. In most patients, VEGF inhibitors can improve vision if macular degeneration is diagnosed early and treated accordingly. However, VEGF inhibitors cannot repair damage that has already occurred. Current AMD research is trying to find treatments for dry AMD and other options for wet AMD. This review provides a summary of the current evidence regarding the different treatments aimed at both forms of AMD with particular and greater attention to the dry form.},
}
@article {pmid39684332,
year = {2024},
author = {Abdouh, M and Chen, Y and Goyeneche, A and Burnier, MN},
title = {Blue Light-Induced Mitochondrial Oxidative Damage Underlay Retinal Pigment Epithelial Cell Apoptosis.},
journal = {International journal of molecular sciences},
volume = {25},
number = {23},
pages = {},
pmid = {39684332},
issn = {1422-0067},
support = {196608b//Alcon Research LLC/ ; },
mesh = {Humans ; *Apoptosis ; *Retinal Pigment Epithelium/metabolism/radiation effects/pathology ; *Oxidative Stress ; *Reactive Oxygen Species/metabolism ; *Mitochondria/metabolism ; *Light/adverse effects ; *Membrane Potential, Mitochondrial ; Proteomics/methods ; Cell Survival/radiation effects ; Cell Line ; Antioxidants/metabolism/pharmacology ; Cell Proliferation ; Epithelial Cells/metabolism ; Blue Light ; },
abstract = {Reactive oxygen species (ROS) play a pivotal role in apoptosis. We reported that Blue Light (BL) induced oxidative stress in human retinal pigment epithelial (RPE) cells in vitro and increased drusen deposition and RPE cell apoptosis in human eyes. Here, we investigated the mechanisms underlying BL-induced damage to RPE cells. Cells were exposed to BL with or without the antioxidant N-acetylcysteine. Cells were analyzed for levels of ROS, proliferation, viability, and mitochondria membrane potential (ΔΨM) fluctuation. We performed proteomic analyses to search for differentially expressed proteins. ROS levels increased following RPE cell exposure to BL. While ROS production did not affect RPE cell proliferation, it was accompanied by decreased ΔΨM and increased cell apoptosis due to the caspase cascade activation in a ROS-dependent manner. Proteomic analyses revealed that BL decreased the levels of ROS detoxifying enzymes in exposed cells. We conclude that BL-induced oxidative stress is cytotoxic to RPE cells. These findings bring new insights into the involvement of BL on RPE cell damage and its role in the progression of age-related macular degeneration. The use of antioxidants is an avenue to block or delay BL-mediated RPE cell apoptosis to counteract the disease progression.},
}
@article {pmid39683933,
year = {2024},
author = {Stefanova, NA and Sotnikova, YS and Osechkova, AE and Karpova, EV and Polovyanenko, DN and Fursova, AZ and Kiseleva, DA and Tolstikova, TG and Kolosova, NG and Bagryanskaya, EG},
title = {Invisible but Insidious Effects of Microplastics.},
journal = {Molecules (Basel, Switzerland)},
volume = {29},
number = {23},
pages = {},
pmid = {39683933},
issn = {1420-3049},
mesh = {Animals ; *Microplastics/toxicity ; Rats ; *Rats, Wistar ; *Cataract/chemically induced/etiology ; Male ; Aging/drug effects ; Macular Degeneration/chemically induced ; Polyethylene Terephthalates/chemistry ; Memory/drug effects ; Female ; Spatial Learning/drug effects ; },
abstract = {Increasing evidence on the adverse health impacts of microplastics (MPs) is available, but their associated risks to the well-being of humans and long-term impacts are poorly understood. An indicator of the remote effects of MPs may be their influence on the rate of aging. To assess the effects of MPs on the aging process, we used accelerated senescence OXYS rats that develop a complex of geriatric diseases. We prepared the polyethylene terephthalate MPs (2-6 microns in size) and in OXYS and Wistar (maternal strain) rats assessed the influence of chronic administration of MPs (10 or 100 mg/kg per day from age 1.5 to 3.5 months,) on the hematological and biochemical blood parameters, spatial learning, and memory. In addition, the effects of MPs on the development of cataracts and retinopathy, similar to age-related macular degeneration (AMD), in OXYS rats were assessed. We found that in the absence of significant changes in standard clinical blood parameters, chronic MP administration negatively affected the cognitive functions of both Wistar rats and OXYS rats. Additionally, a dose of 100 mg/kg MPs contributed to cataract and AMD progression in OXYS rats. Our results suggest that MPs may increase the rate of aging and, in the long term, lifespan.},
}
@article {pmid39683519,
year = {2024},
author = {Figueiredo, I and Farinha, C and Barreto, P and Coimbra, R and Pereira, P and Marques, JP and Pires, I and Cachulo, ML and Silva, R},
title = {Nutritional Genomics: Implications for Age-Related Macular Degeneration.},
journal = {Nutrients},
volume = {16},
number = {23},
pages = {},
pmid = {39683519},
issn = {2072-6643},
mesh = {Humans ; *Macular Degeneration/genetics/prevention &amp; control ; *Nutrigenomics ; *Dietary Supplements ; *Genetic Predisposition to Disease ; Randomized Controlled Trials as Topic ; Diet ; },
abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of vision loss in older individuals, driven by a multifactorial etiology involving genetic, environmental, and dietary factors. Nutritional genomics, which studies gene-nutrient interactions, has emerged as a promising field for AMD prevention and management. Genetic predispositions, such as variants in CFH, C3, C2/CFB, APOE, and oxidative stress pathways, significantly affect the risk and progression of AMD. Methods: This narrative review synthesizes findings from randomized controlled trials and recent advances in nutritional genomics research. It examines the interplay between genetic predispositions and dietary interventions, exploring how personalized nutritional strategies can optimize AMD management. Results and Discussion: The AREDS and AREDS2 trials demonstrated that supplements, including vitamins C, E, zinc, copper, lutein, and zeaxanthin, can reduce the progression to advanced AMD. Nutritional interventions tailored to genetic profiles show promise: CFH risk alleles may enhance zinc supplementation's anti-inflammatory effects, while APOE variants influence the response to omega-3 fatty acids. Adjusting carotenoid intake, such as lutein and zeaxanthin, based on genetic susceptibility exemplifies emerging precision nutritional approaches. Ongoing research seeks to integrate nutrigenomic testing into clinical settings, enabling clinicians to tailor interventions to individual genetic profiles. Conclusions: Further studies are needed to assess the long-term effects of personalized interventions, investigate additional genetic variants, and develop tools for clinical implementation of nutrigenomics. Advancing these strategies holds the potential to improve patient outcomes, optimize AMD management, and pave the way for precision nutrition in ophthalmology.},
}
@article {pmid39682561,
year = {2024},
author = {Savastano, MC and Crincoli, E and Toto, L and Grassi, MO and Chiosi, F and Savastano, A and Rizzo, C and Mastropasqua, R and Boscia, F and Rizzo, S},
title = {Regression of the Flow Signal from the Neovascular Network in AMD Neovascular Membranes Treated with Faricimab.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {23},
pages = {},
pmid = {39682561},
issn = {2075-4418},
abstract = {OBJECTIVES: To report the occurrence of the regression of the flow signal from the neovascular network in macular neovascularizations (MNVs), developing in the context of age-related macular degeneration (AMD), treated with faricimab in a treat-and-extend regimen.<br><br>METHODS: Eyes affected by AMD-related MNV and treated with faricimab intravitreal injections in a treat-and-extend (TE) regimen were consecutively retrospectively screened in five specialized retina centers. Changes in neovascular network characteristics during the course of the treatment were analyzed. The availability of high-quality optical coherence tomography angiography (OCTA) at the beginning of the treatment and at the regression of the MNV was necessary for inclusion. According to greatest linear diameter (GLD) changes during treatment, eyes were divided into three groups: a complete regression (CR) group, a partial remission (PR) group (a reduction of at least 50% of the GLD from baseline to last follow-up), and a stable group (stable/showing a reduction lower than 50% of the GLD from baseline to follow up).<br><br>RESULTS: One hundred and ten (110) eyes were included. The CR group was composed of 12 eyes (10.9%), while the PR group represented 60.9% of the study population. CR occurred after a mean of 6.0 &#xb1; 1.4 months, ranging from 4 to 8 months. Time to regression was significantly lower in eyes na&#xef;ve to treatment before the study compared with the others (p = 0.022). A significantly lower baseline GLD was detected in the CR group (1292.2 &#xb1; 195.6 &#x3bc;m) compared with the PR group (1324.6 &#xb1; 135.6 &#x3bc;m) and the stable group (1412.5 &#xb1; 110.9 &#x3bc;m) (omnibus p = 0.003).<br><br>CONCLUSIONS: Complete regression of the flow signal from the MNV neovascular network documented with OCTA may occur during TE regimens with faricimab. In treatment-na&#xef;ve eyes, regression occurs earlier during the treatment.},
}
@article {pmid39682518,
year = {2024},
author = {Ragni, F and Bovo, S and Zen, A and Sona, D and De Nadai, K and Adamo, GG and Pellegrini, M and Nasini, F and Vivarelli, C and Tavolato, M and Mura, M and Parmeggiani, F and Jurman, G},
title = {Session-by-Session Prediction of Anti-Endothelial Growth Factor Injection Needs in Neovascular Age-Related Macular Degeneration Using Optical-Coherence-Tomography-Derived Features and Machine Learning.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {23},
pages = {},
pmid = {39682518},
issn = {2075-4418},
support = {RF-2016-02362267//Ministry of Health, Italy/ ; },
abstract = {BACKGROUND/OBJECTIVES: Neovascular age-related macular degeneration (nAMD) is a retinal disorder leading to irreversible central vision loss. The pro-re-nata (PRN) treatment for nAMD involves frequent intravitreal injections of anti-VEGF medications, placing a burden on patients and healthcare systems. Predicting injections needs at each monitoring session could optimize treatment outcomes and reduce unnecessary interventions.<br><br>METHODS: To achieve these aims, machine learning (ML) models were evaluated using different combinations of clinical variables, including retinal thickness and volume, best-corrected visual acuity, and features derived from macular optical coherence tomography (OCT). A "Leave Some Subjects Out" (LSSO) nested cross-validation approach ensured robust evaluation. Moreover, the SHapley Additive exPlanations (SHAP) analysis was employed to quantify the contribution of each feature to model predictions.<br><br>RESULTS: Results demonstrated that models incorporating both structural and functional features achieved high classification accuracy in predicting injection necessity (AUC = 0.747 &#xb1; 0.046, MCC = 0.541 &#xb1; 0.073). Moreover, the explainability analysis identified as key predictors both subretinal and intraretinal fluid, alongside central retinal thickness.<br><br>CONCLUSIONS: These findings suggest that session-by-session prediction of injection needs in nAMD patients is feasible, even without processing the entire OCT image. The proposed ML framework has the potential to be integrated into routine clinical workflows, thereby optimizing nAMD therapeutic management.},
}
@article {pmid39681731,
year = {2025},
author = {Jauch, AS and Ach, T},
title = {[Climate change as a factor in the development of retinal diseases: a critical review].},
journal = {Die Ophthalmologie},
volume = {122},
number = {1},
pages = {26-30},
pmid = {39681731},
issn = {2731-7218},
mesh = {Humans ; *Climate Change ; *Retinal Diseases/etiology/epidemiology/diagnosis ; Risk Factors ; },
abstract = {The climate change has multiple effects on health. The eyes are not exempt from these effects and components of climate change, such as the temperature, UV radiation or air pollution that can have a relevant impact on retinal pathologies can be worked out. The alterations to the retina include UV light-induced retinal damage, age-related macular degeneration (AMD), choroidal melanoma, diabetic retinopathy, retinal detachment and vascular occlusion. Overall, there is an urgent need for prospective multicenter studies to be able to further analyze the specific impact of components of climate change on the retina.},
}
@article {pmid39680968,
year = {2024},
author = {Owen, JJ and Long, S and Mullinax, K and Griffin, J},
title = {Bevacizumab-induced subungual hemorrhage.},
journal = {Dermatology online journal},
volume = {30},
number = {5},
pages = {},
doi = {10.5070/D330564427},
pmid = {39680968},
issn = {1087-2108},
mesh = {Humans ; *Bevacizumab/adverse effects/therapeutic use ; Female ; Aged ; *Angiogenesis Inhibitors/adverse effects ; *Hemorrhage/chemically induced ; *Nail Diseases/chemically induced ; Intravitreal Injections ; Wet Macular Degeneration/drug therapy ; },
abstract = {Exudative (wet) age-related macular degeneration can be treated with the vascular endothelial growth factor (VEGF)-inhibiting monoclonal antibody bevacizumab. Currently, bevacizumab therapy is associated with known skin-related side effects, such as rash, mucosal hemorrhage, and hemorrhagic ulcers. While subungual "splinter" hemorrhage is a documented side effect of VEGF receptor antagonists and Raf protein inhibitors, there are no prior reports of bevacizumab-induced subungual hemorrhage to the best of our knowledge. Thus, we present the case of a 71-year-old female diagnosed with bilateral age-related macular degeneration, who, during six months of intravitreal bevacizumab treatment, began noticing fingernail discoloration, described as similar to that of a bruise. Given our patient's history of bevacizumab therapy and the documented reports of bevacizumab-associated mucosal and ulcerative hemorrhage, we hypothesize that the discoloration and hemorrhage are likely unreported adverse effects associated with bevacizumab therapy.},
}
@article {pmid39679976,
year = {2024},
author = {Zhu, M and Yu, J},
title = {Identification of Ferroptosis-Related Gene in Age-Related Macular Degeneration Using Machine Learning.},
journal = {Immunity, inflammation and disease},
volume = {12},
number = {12},
pages = {e70059},
pmid = {39679976},
issn = {2050-4527},
mesh = {*Ferroptosis/genetics ; *Macular Degeneration/genetics/metabolism/pathology/diagnosis ; Humans ; *Machine Learning ; Retinal Pigment Epithelium/metabolism/pathology ; Animals ; Mice ; Gene Expression Profiling ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a major cause of irreversible visual impairment, with dry AMD being the most prevalent form. Programmed cell death of retinal pigment epithelium (RPE) cells is a central mechanism in the pathogenesis of dry AMD. Ferroptosis, a recently identified form of programmed cell death, is characterized by iron accumulation-induced lipid peroxidation. This study aimed to investigate the involvement of ferroptosis in the progression of AMD.<br><br>METHODS: A total of 41 samples of AMD and 50 normal samples were obtained from the data set GSE29801 for differential gene expression analysis and functional enrichment. Differentially expressed genes (DEGs) were selected and intersected with genes from the ferroptosis database to obtain differentially expressed ferroptosis-associated genes (DEFGs). Machine learning algorithms were employed to screen diagnostic genes. The diagnostic genes were subjected to Gene Set Enrichment Analysis (GSEA). Expression differences of diagnostic genes were validated in in vivo and in vitro models.<br><br>RESULTS: We identified 462 DEGs when comparing normal and AMD samples. The GO enrichment analysis indicated significant involvement in key biological processes like collagen-containing extracellular matrix composition, positive cell adhesion regulation, and extracellular matrix organization. Through the intersection with ferroptosis gene sets, we pinpointed 10 DEFGs. Leveraging machine learning algorithms, we pinpointed five ferroptosis feature diagnostic genes: VEGFA, SLC2A1, HAMP, HSPB1, and FADS2. The subsequent experiments validated the increased expression of SLC2A1 and FADS2 in the AMD ferroptosis model.<br><br>CONCLUSION: The occurrence of ferroptosis could potentially contribute to the advancement of AMD. SLC2A1 and FADS2 have demonstrated promise as emerging diagnostic biomarkers and plausible therapeutic targets for AMD.},
}
@article {pmid39678939,
year = {2024},
author = {Rana, NA and Chalasani, M and Markle, J and Russell, MW and Li, A and Talcott, KE and Singh, RP and Sharma, S},
title = {Evaluation of Sustained Intraocular Pressure Elevations Across Antivascular Endothelial Growth Factor Agents.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264241304813},
pmid = {39678939},
issn = {2474-1272},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
abstract = {Purpose: To evaluate the effect of antivascular endothelial growth factor (anti-VEGF) agents on the development of sustained intraocular pressure (IOP) elevations. Methods: This single-center retrospective cohort study included eyes receiving anti-VEGF injections for various indications along with nontreated fellow eyes from 2012 to 2022. Patients were grouped according to treatment with bevacizumab, ranibizumab, or aflibercept. Trends in IOP were recorded after treatment initiation for 1 year. The development of sustained IOP elevations (defined as an increase of 5 mm Hg or greater than baseline for 4 or more weeks) and glaucoma manifestations were recorded. Results: The analysis included 1604 eyes (injection cohort, 907; control cohort, 697). The mean age of the injection cohort was 83.3 years; 56.9% were women and 82.0% were White. Injections were for neovascular age-related macular degeneration (498 [54.9%]), diabetic retinopathy (219 [24.1%]), retinal vein occlusion (161 [17.8%]), and other indications (29 [3.2%)]. Bevacizumab was used in 521 eyes (57.4%), ranibizumab in 129 eyes (14.2%), and aflibercept in 257 eyes (28.3%). The mean age in the control cohort was 81.6 years; 56.1% were women and 84.1% were White. Sustained IOP elevations developed in 97 (6.0%) of 1604 eyes throughout the study. Compared with controls, treated eyes overall did not have an increased rate of sustained IOP elevations (P = .38) or glaucoma progression (P = .51), although patients treated with bevacizumab had a significantly greater incidence of IOP elevation than controls (relative risk, 1.81; 95% CI, 1.18-2.78). The mean number of injections to sustained IOP elevation was 5.4 and did not differ between agents (P > .05). Conclusions: Although not all anti-VEGF agents are associated with IOP-related adverse effects, bevacizumab carries an increased risk for sustained IOP elevation. Further investigation into the long-term effects of bevacizumab on IOP and glaucoma and a comparison with other anti-VEGF agents may be warranted.},
}
@article {pmid39678047,
year = {2024},
author = {Xu, C and Fu, X and Qin, H and Yao, K},
title = {Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1499719},
pmid = {39678047},
issn = {1662-5102},
abstract = {DNA methylation plays a crucial role in development, aging, degeneration of various tissues and dedifferentiated cells. This review explores the multifaceted impact of DNA methylation on the retina and brain during development and pathological processes. First, we investigate the role of DNA methylation in retinal development, and then focus on retinal diseases, detailing the changes in DNA methylation patterns in diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. Since the retina is considered an extension of the brain, its unique structure allows it to exhibit similar immune response mechanisms to the brain. We further extend our exploration from the retina to the brain, examining the role of DNA methylation in brain development and its associated diseases, such as Alzheimer's disease (AD) and Huntington's disease (HD) to better understand the mechanistic links between retinal and brain diseases, and explore the possibility of communication between the visual system and the central nervous system (CNS) from an epigenetic perspective. Additionally, we discuss neurodevelopmental brain diseases, including schizophrenia (SZ), autism spectrum disorder (ASD), and intellectual disability (ID), focus on how DNA methylation affects neuronal development, synaptic plasticity, and cognitive function, providing insights into the molecular mechanisms underlying neurodevelopmental disorders.},
}
@article {pmid39677855,
year = {2024},
author = {Galeone, C and Turati, F and Nicolò, M and Parravano, M and Vujosevic, S and Bianchino, L and Sicari, E and Lanzetta, P},
title = {Faricimab versus the standard of care for neovascular age-related macular degeneration in Italy: an indirect treatment comparison.},
journal = {Drug target insights},
volume = {18},
number = {},
pages = {105-111},
pmid = {39677855},
issn = {1177-3928},
abstract = {OBJECTIVES: To assess through an indirect treatment comparison (ITC) the potential benefit of faricimab over the anti-vascular endothelial growth factor (VEGF) real-life scenario, hereby defined standard of care (SoC), in Italy, that is, aflibercept, bevacizumab, and ranibizumab, in patients with neovascular age-related macular degeneration (nAMD) naïve to any anti-VEGF treatment.<br><br>METHODS: Individual patient-level data from the phase III clinical trials TENAYA and LUCERNE (faricimab cohort) and the real-world study RADIANCE (RADIANCE cohort) were used. Efficacy was evaluated with changes in best corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to 1 year (week 52 in the RADIANCE and week 48 in the faricimab cohorts, respectively). Propensity score-based inverse probability of treatment weighting was utilized to balance cohorts and mitigate bias due to potential confounding. Sensitivity analyses were performed to evaluate treatment differences adjusted for the number of injections.<br><br>RESULTS: The ITC included 513 patients treated with faricimab and 263 patients treated with SoC. At 1 year, faricimab showed a greater mean BCVA gain (treatment difference +5.4 letters, p<0.001) and CST reduction (treatment difference -71.8 &#x3bc;m, p<0.001) compared to SoC. Sensitivity analyses confirmed the robustness of results, showing a BCVA improvement of +4.0 letters and a CST reduction of -71.5 &#x3bc;m in favor of faricimab.<br><br>CONCLUSIONS: Despite the limitations due to the use of ITC and the comparison between clinical trials and real-world cohorts, the present analysis suggests potential benefits in terms of vision gain and CST reduction in na&#xef;ve nAMD patients treated with faricimab compared with SoC in a real-world setting.},
}
@article {pmid39677811,
year = {2025},
author = {Donaldson, KJ and Chrenek, MA and Boatright, JH and Nickerson, JM},
title = {High resolution imaging and interpretation of three-dimensional RPE sheet structure.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39677811},
issn = {2692-8205},
support = {R01 EY028859/EY/NEI NIH HHS/United States ; P30 EY006360/EY/NEI NIH HHS/United States ; I21 RX001924/RX/RRD VA/United States ; R01 DC009246/DC/NIDCD NIH HHS/United States ; T32 EY007092/EY/NEI NIH HHS/United States ; I01 RX002806/RX/RRD VA/United States ; R01 EY021592/EY/NEI NIH HHS/United States ; R01 EY028450/EY/NEI NIH HHS/United States ; },
abstract = {The retinal pigment epithelium (RPE), a monolayer of pigmented cells, is critical for visual function through its interaction with the neural retina. In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), dysmorphic traits like cell enlargement and apparent multinucleation emerge. Multinucleation has been hypothesized to result from cellular fusion, a compensatory mechanism to maintain cell to cell contact, barrier function, and conserve resources in unhealthy tissue. However, traditional two-dimensional (2D) imaging using apical border markers alone may misrepresent multinucleation due to the lack of lateral markers. We present high-resolution confocal images enabling three-dimensional (3D) visualization of apical (ZO-1) and lateral (alpha-catenin) markers alongside nuclei. In two RPE damage models, we find that seemingly multinucleated cells are often single cells with displaced neighboring nuclei and lateral membranes. This emphasizes the need for 3D analyses to avoid misinterpreting multinucleation and underlying fusion mechanisms. Lastly, images from the NaIO3 oxidative damage model reveal variability in RPE damage, with elongated, dysmorphic cells showing increased ZsGreen reporter protein expression driven by EMT-linked CAG promoter activity, while more regular RPE cells displayed somewhat reduced green signal more typical of epithelial phenotypes.},
}
@article {pmid39677279,
year = {2024},
author = {Alsatrawi, AB},
title = {Assessing Choroidal Neovascular Membrane Flow Regression Using Optical Coherence Tomography Angiography After a Single Injection of Faricimab in Age-Related Macular Degeneration: A Case Study.},
journal = {Cureus},
volume = {16},
number = {11},
pages = {e73760},
pmid = {39677279},
issn = {2168-8184},
abstract = {This case study aims to evaluate the regression of the vascular network in a patient with age-related macular degeneration (AMD) following a single injection of faricimab, utilizing optical coherence tomography angiography (OCTA) for detailed assessment. An elderly patient diagnosed with neovascular AMD received a single injection of faricimab, with pre and post-treatment OCTA imaging performed to assess changes in the choroidal neovascular membrane (CNVm) and surrounding retinal structures. OCTA revealed significant regression of the vascular network following the single injection of faricimab, demonstrating a marked reduction in blood flow within the CNV, which corresponded with structural and anatomical improvements in the retina. This case highlights the potential of faricimab to induce rapid regression of CNVm in AMD after a single injection, as observed through OCTA. Furthermore, while current monitoring primarily relies on OCT B-scan structural assessments, the flow dynamics captured by OCTA may play a crucial role in future treatment monitoring and therapeutic strategies for managing neovascular AMD.},
}
@article {pmid39677217,
year = {2024},
author = {Gupta, A and Al-Kazwini, H},
title = {Evaluating ChatGPT's Diagnostic Accuracy in Detecting Fundus Images.},
journal = {Cureus},
volume = {16},
number = {11},
pages = {e73660},
pmid = {39677217},
issn = {2168-8184},
abstract = {Introduction Artificial intelligence is rapidly advancing in healthcare. Ophthalmology, with its reliance on imaging for diagnosis and management, has the potential to benefit from this technology. Deep learning models are currently used in image analysis in ophthalmology. ChatGPT (OpenAI, San Francisco, CA), a large language model, has recently expanded to include image analysis, creating new opportunities for diagnostic applications. While prior research shows potential in text-based diagnostics for ophthalmology, there is limited literature on AI's diagnostic accuracy in interpreting retinal images. Methods We selected 12 fundus images from key diseases identified by the Royal College of Ophthalmology curricula for medical students, foundation doctors, and trainees. Each image was presented to ChatGPT 4.0 using a standardised prompt to identify the most likely diagnosis. Responses were recorded, and the model's accuracy was assessed by comparing its diagnoses to the confirmed conditions. Results ChatGPT accurately diagnosed four out of 12 diseases (papilloedema, dry age-related macular degeneration (ARMD), glaucoma and vitreous haemorrhage) and provided one partially correct diagnosis (diabetic retinopathy). However, the model struggled with seven cases, including central retinal artery occlusion, central retinal vein occlusion, dry ARMD, rhegmatogenous retinal detachment, tractional retinal detachment, epiretinal membrane and macular hole. Conclusion ChatGPT demonstrates the potential for diagnosis of retinal conditions from fundus photography. However, it currently lacks the accuracy required for clinical application; the model often hallucinates when unsure, which has diagnostic implications. Further work is required to refine these models and expand their diagnostic potential.},
}
@article {pmid39676771,
year = {2024},
author = {Heloterä, H and Viita, AM and Laine, J},
title = {Evolution of Workload Associated with Anti-VEGF Treatments for AMD, DME, RVO and mCNV in Hospital District of Southwest Finland.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3645-3655},
pmid = {39676771},
issn = {1177-5467},
abstract = {BACKGROUND: The prevalence of vision-threatening diseases, such as age-related macular degeneration (AMD) and diabetic macular edema (DME), is likely to increase in developed countries owing to an aging population, rising life expectancy, and unfavorable lifestyle changes. Increases in the burden of vision-threatening diseases pose a challenge to the healthcare system. After the emergence of intravitreal anti-VEGF inhibitors, treatment options for neovascular AMD (nAMD), DME, retinal vein occlusion (RVO) and myopic choroidal neovascularization (myopic CNV) have increased. As this change in treatment practices has occurred over the last two decades, it is important to demonstrate changes in patient numbers and administered treatments to provide solutions for handling the workload and productivity in ophthalmology departments. In addition, the registry data landscape has evolved in Finland in recent years. Thus, understanding the possibilities and limitations of ophthalmology registries and patient information systems is required.<br><br>METHODS: This study involved the secondary use of retrospectively registered data from the data warehouse of the Hospital District of Southwest Finland. Our goal was to explore how the workload of ophthalmology departments caused by intravitreal injections has evolved from 2015 to 2022.<br><br>RESULTS: The ophthalmology department workload increased significantly during our observation period as the total number of patients receiving intravitreal treatments for nAMD, DME, RVO, and myopic CNV increased 199.6% from 2015 to 2021. In addition, the total number of administered anti-VEGF injections increased during our observation period, but the increase rate began to subside (2019-2020: increase 23.7%, 2020-2021: increase 10.3%, 2021-2022: increase 6.7%).<br><br>CONCLUSION: Supporting the utilization of registry data is essential in evidence-based discussions evolving workload in healthcare. However, it is important to understand the limitations and the quality of the registries. Our study contributes to better understanding the Finnish registry perspective, and it demonstrates the increase in workload in ophthalmology departments caused by intravitreal injections.},
}
@article {pmid39675993,
year = {2024},
author = {Hsu, TK and Lai, IP and Tsai, MJ and Lee, PJ and Hung, KC and Yang, S and Chan, LW and Lin, IC and Chang, WH and Huang, YJ and Cheng, MC and Hsieh, YT},
title = {A deep learning approach for the screening of referable age-related macular degeneration - Model development and external validation.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2024.12.008},
pmid = {39675993},
issn = {0929-6646},
abstract = {PURPOSE: To develop a deep learning image assessment software, VeriSee™ AMD, and to validate its accuracy in diagnosing referable age-related macular degeneration (AMD).<br><br>METHODS: For model development, a total of 6801 judgable 45-degree color fundus images from patients, aged 50 years and over, were collected. These images were assessed for AMD severity by ophthalmologists, according to the Age-Related Eye Disease Studies (AREDS) AMD category. Referable AMD was defined as category three (intermediate) or four (advanced). Of these images, 6123 were used for model training and validation. The other 678 images were used for testing the accuracy of VeriSee&#x2122; AMD relative to the ophthalmologists. Area under the receiver operating characteristic curve (AUC) for VeriSee&#x2122; AMD, and the sensitivities and specificities for VeriSee&#x2122; AMD and ophthalmologists were calculated. For external validation, another 937 color fundus images were used to test the accuracy of VeriSee&#x2122; AMD.<br><br>RESULTS: During model development, the AUC for VeriSee&#x2122; AMD in diagnosing referable AMD was 0.961. The accuracy for VeriSee&#x2122; AMD for testing was 92.04% (sensitivity 90.0% and specificity 92.43%). The mean accuracy of the ophthalmologists in diagnosing referable AMD was 85.8% (range: 75.93%-97.31%). During external validation, VeriSee AMD achieved a sensitivity of 90.03%, a specificity of 96.44%, and an accuracy of 92.04%.<br><br>CONCLUSIONS: VeriSee&#x2122; AMD demonstrated good sensitivity and specificity in diagnosing referable AMD from color fundus images. The findings of this study support the use of VeriSee&#x2122; AMD in assisting with the clinical screening of intermediate and advanced AMD using color fundus photography.},
}
@article {pmid39673553,
year = {2024},
author = {Usoltseva, AS and Litwin, C and Lee, M and Hill, C and Cai, J and Chen, Y},
title = {Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {38},
number = {24},
pages = {e70249},
pmid = {39673553},
issn = {1530-6860},
support = {R01 EY028773/EY/NEI NIH HHS/United States ; R01EY028773//HHS | National Institutes of Health (NIH)/ ; //Research to Prevent Blindness/ ; R01EY026999//HHS | National Institutes of Health (NIH)/ ; M2017186//BrightFoucs Foundation/ ; R01EY034742//HHS | National Institutes of Health (NIH)/ ; //Presbyterian Health Foundation (PHF)/ ; P30EY027125//HHS | National Institutes of Health (NIH)/ ; P30 EY021725/EY/NEI NIH HHS/United States ; R01 EY026999/EY/NEI NIH HHS/United States ; //Harold Hamm Diabetes Center/ ; //VitreoRetinal Surgery Foundation (VRSF)/ ; R01 EY034742/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology ; *Phosphatidate Phosphatase/metabolism/genetics ; Animals ; *Homeostasis ; Mice ; *Lipid Metabolism/physiology ; *Mice, Knockout ; Macular Degeneration/metabolism/pathology/genetics ; Mice, Inbred C57BL ; Humans ; Male ; },
abstract = {Dysregulated lipid metabolism, characterized by the accumulation of lipid deposits on Bruch's membrane and in drusen, is considered a key pathogenic event in age-related macular degeneration (AMD). The imbalance of lipid production, usage, and transport in local tissues, particularly in the retinal pigment epithelium (RPE), is increasingly recognized as crucial in AMD development. However, the molecular mechanisms governing lipid metabolism in the RPE remain elusive. LIPIN1, a multifunctional protein acting as both a modulator of transcription factors and a phosphatidate phosphatase (PAP1), is known to play important regulatory roles in lipid metabolism and related biological functions, such as inflammatory responses. While deficits in LIPIN1 have been linked to multiple diseases, its specific roles in the retina and RPE remain unclear. In this study, we investigated LIPIN1 in RPE integrity and function using a tissue-specific knockout animal model. The clinical and histological examinations revealed age-dependent degeneration in the RPE and the retina, along with impaired lipid metabolism. Bulk RNA sequencing indicated a disturbance in lipid metabolic pathways. Moreover, these animals exhibited inflammatory markers reminiscent of human AMD features, including deposition of IgG and C3d on Bruch's membrane. Collectively, our findings indicate that LIPIN1 is a critical component of the complex regulatory network of lipid homeostasis in the RPE. Disruption of LIPIN1-mediated regulation impaired lipid balance and contributed to AMD-related pathogenic changes.},
}
@article {pmid39673040,
year = {2025},
author = {Loewenstein, A and Sylvanowicz, M and Amoaku, WM and Aslam, T and Cheung, CMG and Eldem, B and Finger, RP and Gale, RP and Kodjikian, L and Koh, A and Korobelnik, JF and Lin, X and Mitchell, P and Murphy, M and Okada, M and Pearce, I and Rodriguez, FJ and Stern, J and Talks, SJ and Wong, DT and Wong, TY and Ziemssen, F and Barratt, J},
title = {Global Insights from Patients, Providers, and Staff on Challenges and Solutions in Managing Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {1},
pages = {211-228},
pmid = {39673040},
issn = {2193-8245},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration is a global public-health concern, associated with a considerable burden to individuals, healthcare systems, and society. The objective of this study was to understand different perspectives on the challenges associated with the clinical management of neovascular age-related macular degeneration, which could elucidate measures to comprehensively improve clinical care and outcomes.<br><br>METHODS: A survey was carried out of patients with neovascular age-related macular degeneration, their providers, and clinic staff in 77 clinics across 24 countries on six continents, from a diverse range of healthcare systems, settings, and reimbursement models. Surveys comprised a series of single/multiple-response questions completed anonymously. Data gathered included patient personal characteristics, appointment attendance challenges, treatment experiences, and opportunities to improve support. Provider and clinic staff surveys asked similar questions about their perspectives; clinic characteristics were also captured.<br><br>RESULTS: There were 6425 responses; 4558 patients with neovascular age-related macular degeneration, 659 providers, and 1208 clinic staff. Challenges identified included concern about patient burden to family/friends, high frequency of treatment, difficulties in traveling to appointments, long waiting times, and insufficient comprehension of neovascular age-related macular degeneration. Participants identified logistical (improved financial assistance with treatment and out-of-pocket costs, and appointment reminders), operational (addressing clinic set up to reduce waiting times and improving the amount of time providers spend with patients), and educational (improving quality and provision of patient information and expectation-setting) opportunities to improve care.<br><br>CONCLUSIONS: The wealth of data generated by this global survey highlights the breadth of challenges associated with clinical management of patients with neovascular age-related macular degeneration. Addressing the opportunities raised could improve patient adherence to treatment and potentially outcomes, reduce appointment burden, and increase clinic capacity.},
}
@article {pmid39672991,
year = {2025},
author = {Banerjee, R and Mujib, R and Sanyal, P and Chakraborti, T and Saha, SK},
title = {Pan-Ret: a semi-supervised framework for scalable detection of pan-retinal diseases.},
journal = {Medical &amp; biological engineering &amp; computing},
volume = {63},
number = {4},
pages = {959-974},
pmid = {39672991},
issn = {1741-0444},
mesh = {Humans ; *Retinal Diseases/diagnosis/diagnostic imaging ; Support Vector Machine ; Algorithms ; Retina/diagnostic imaging ; *Image Interpretation, Computer-Assisted/methods ; *Image Processing, Computer-Assisted/methods ; },
abstract = {It has been shown in recent years that a range of optical diseases have early manifestation in retinal fundus images. It is becoming increasingly important to separate the regions of interest (RoI) upfront in the automated classification pipeline in order to ensure the alignment of the disease diagnosis with clinically relevant visual features. In this work, we introduce Pan-Ret, a semi-supervised framework which starts with locating the abnormalities in the biomedically relevant RoIs of a retinal image in an "annotation-agnostic" fashion. It does so by leveraging an anomaly detection setup using parallel autoencoders that are trained only on healthy population initially. Then, the anomalous images are separated based on the RoIs using a fully interpretable classifier like support vector machine (SVM). Experimental results show that the proposed approach yields an overall F1-score of 0.95 and 0.96 in detecting abnormalities on two different public datasets covering a diverse range of retinal diseases including diabetic retinopathy, hypertensive retinopathy, glaucoma, age-related macular degeneration, and several more in a staged manner. Thus, the work presents a milestone towards a pan-retinal disease diagnostic pipeline that can not only cater to the current set of disease classes, but has the capacity of adding further classes down the line. This is due to an anomaly detection style one-class learning setup of the deep autoencoder piece of the proposed pipeline, thus improving the generalizability of this approach compared to usual fully supervised competitors. This is also expected to increase the practical translational potential of Pan-Ret in a real-life scalable clinical setting.},
}
@article {pmid39672501,
year = {2025},
author = {Corydon, TJ and Bek, T},
title = {Multiple gene therapy as a tool for regulating the expression of molecules involved in neovascular age-related macular degeneration.},
journal = {Progress in retinal and eye research},
volume = {104},
number = {},
pages = {101323},
doi = {10.1016/j.preteyeres.2024.101323},
pmid = {39672501},
issn = {1873-1635},
mesh = {Humans ; *Genetic Therapy/methods ; *Vascular Endothelial Growth Factor A/metabolism ; *Macular Degeneration/therapy/genetics ; Serpins/genetics/metabolism ; Eye Proteins/genetics/metabolism ; Nerve Growth Factors/genetics/metabolism ; Animals ; Wet Macular Degeneration/therapy/genetics ; Gene Expression Regulation ; Genetic Vectors ; Dependovirus/genetics ; },
abstract = {Anti-vascular endothelial growth factor (VEGF) therapies have revolutionized the treatment of neovascular age-related macular degeneration (nAMD) and other retinal diseases. However, the necessity for repeated intravitreal injections and the observation of variable treatment responses calls for new treatment modalities where fewer and more effective interventions can result in a clinical effect. Gene therapy might be such an alternative, and therefore the development and clinical application of gene therapy aimed at modifying gene expression has received considerable attention. The article reviews current knowledge of the background, pathophysiological mechanisms, technologies, limitations, and future directions for gene therapy aimed at modifying the synthesis of compounds involved in acquired and senescent retinal disease. The authors have contributed to the field by developing gene therapy to reduce the expression of vascular endothelial growth factor (VEGF), as well as multiple gene therapy for simultaneous downregulation of the synthesis of VEGF and upregulation of pigment epithelium-derived factor (PEDF) using adeno-associated virus (AAV) vectors. It is suggested that such multi-target gene therapy might be included in future treatments of retinal diseases where the underlying mechanisms are complex and cannot be attributed to one specific mediator. Such diseases might include dry AMD (dAMD) with geographic atrophy, but also diabetic macular edema (DME) and retinal vein occlusion (RVO). Gene therapy can be expected to be most beneficial for the patients in need of multiple intra-vitreal injections and in whom the therapeutic response is insufficient. It is concluded, that in parallel with basic research, there is a need for clinical studies aimed at identifying factors that can be used to identify patients who will benefit from gene therapy already at the time of diagnosis of the retinal disease.},
}
@article {pmid39672305,
year = {2025},
author = {Saeed, A and Gin, C and Hodgson, LAB and Jannaud, M and Hadoux, X and Glover, EK and Gee, EE and van Wijngaarden, P and Guymer, RH and Wu, Z},
title = {Local OCT Structural Correlates of Deep Visual Sensitivity Defects in Early Atrophic Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {5},
pages = {412-420},
doi = {10.1016/j.oret.2024.12.007},
pmid = {39672305},
issn = {2468-6530},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Prospective Studies ; Aged ; *Visual Acuity ; *Fluorescein Angiography/methods ; *Visual Fields/physiology ; *Retinal Pigment Epithelium/pathology ; Visual Field Tests/methods ; *Geographic Atrophy/diagnosis/physiopathology ; Middle Aged ; Fundus Oculi ; Aged, 80 and over ; Follow-Up Studies ; },
abstract = {PURPOSE: To determine local OCT structural correlates of deep visual sensitivity defects (threshold of ≤10 decibels on microperimetry) in early atrophic age-related macular degeneration (AMD).<br><br>DESIGN: Prospective observational study.<br><br>PARTICIPANTS: Forty eyes from 40 participants, with at least incomplete retinal pigment epithelium (RPE) and outer retinal atrophy, or more advanced atrophic lesion(s).<br><br>METHODS: Participants underwent &#x2265;2 targeted, high-density microperimetry tests of atrophic lesions of interest in 1 eye, and high-density 3&#xd7;3-mm volume scans of that region on a swept-source OCT angiography device, all at a single visit. Seven OCT-defined features of atrophy were manually annotated: hypertransmission, RPE attenuation/disruption, complete RPE loss, ellipsoid zone disruption, external limiting membrane (ELM) disruption, subsidence of the outer plexiform layer and inner nuclear layer, and/or hyporeflective wedge-shaped band, and outer nuclear layer (ONL) thickness.<br><br>MAIN OUTCOME MEASURES: Association between OCT-defined features of atrophy and presence of a deep visual sensitivity defect at a local, pointwise level.<br><br>RESULTS: All OCT-defined features of atrophy were individually associated with the presence of a deep visual sensitivity defect at a pointwise level in univariable mixed-effects logistic regression analyses (P < 0.001 for all). However, only hypertransmission, complete RPE loss, ELM disruption, and ONL thickness remained significantly and independently associated with deep visual sensitivity defects in a multivariable analysis (P &#x2264; 0.011). A prediction model incorporating these 4 OCT features (partial area under the curve [pAUC] at &#x2265;90% specificity&#xa0;= 0.80) outperformed models using any single feature alone in predicting the presence of deep visual sensitivity defects (pAUC&#xa0;= 0.65 to 0.78, respectively; P &#x2265; 0.040).<br><br>CONCLUSIONS: The study identified hypertransmission, complete RPE loss, ELM disruption, and ONL thickness as key OCT-defined features of atrophy independently associated with deep visual sensitivity defects. These findings are important when considering anatomical outcome measures for evaluating interventions for early atrophic AMD that are most likely to capture beneficial treatment effects that will be accompanied by evidence of functional preservation if measured directly.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39671227,
year = {2024},
author = {Goerdt, L and Swain, TA and Kar, D and McGwin, G and Berlin, A and Clark, ME and Owsley, C and Sloan, KR and Curcio, CA},
title = {Band Visibility in High-Resolution Optical Coherence Tomography Assessed With a Custom Review Tool and Updated, Histology-Derived Nomenclature.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {12},
pages = {19},
pmid = {39671227},
issn = {2164-2591},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {*Tomography, Optical Coherence/methods ; Humans ; Adult ; Aged ; *Terminology as Topic ; *Macular Degeneration/pathology/diagnostic imaging ; *Aging ; Young Adult ; Male ; Female ; Retina/diagnostic imaging ; Aged, 80 and over ; Middle Aged ; Reproducibility of Results ; },
abstract = {PURPOSE: For structure-function research at the transition of aging to age-related macular degeneration, we refined the current consensus optical coherence tomography (OCT) nomenclature and evaluated a novel review software for investigational high-resolution OCT imaging (HR-OCT; <3 µm axial resolution).<br><br>METHOD: Volume electron microscopy, immunolocalizations, histology, and investigational devices informed a refined OCT nomenclature for a custom ImageJ-based review tool to assess retinal band visibility. We examined effects on retinal band visibility of automated real-time averaging (ART) 9 and 100 (11 eyes of 10 healthy young adults), aging (10 young vs 22 healthy aged), and age-related macular degeneration (AMD; 22 healthy aged, 17 early (e)AMD, 15 intermediate (i)AMD). Intrareader reliability was assessed.<br><br>RESULTS: Bands not included in consensus nomenclature are now visible using HR-OCT: inner plexiform layer (IPL) 1-5, outer plexiform layer (OPL) 1-2, outer segment interdigitation zone 1-2 (OSIZ, including hyporeflective outer segments), and retinal pigment epithelium (RPE) 1-5. Cohen's kappa was 0.54-0.88 for inner and 0.67-0.83 for outer retinal bands in a subset of 10 eyes. IPL-3-5 and OPL-2 visibility benefitted from increased ART. OSIZ-2 and RPE-1,2,3,5 visibility was worse in aged eyes than in young eyes. OSIZ-1-2, RPE-1, and RPE-5 visibility decreased in eAMD and iAMD compared to healthy aged eyes.<br><br>CONCLUSIONS: We reliably identified 28 retinal bands using a novel review tool for HR-OCT. Image averaging improved inner retinal band visibility. Aging and AMD development impacted outer retinal band visibility.<br><br>TRANSLATIONAL SIGNIFICANCE: Detailed knowledge of anatomic structures visible on OCT will enhance precision in research, including AI training and structure-function analyses.},
}
@article {pmid39669991,
year = {2024},
author = {Liu, S and Zheng, M and Sun, H and Pan, C and Li, D and Zhou, X and Zheng, Z},
title = {Analysis of factors affecting prognosis of the visual acuity and baseline risk factors for subretinal fibrosis in neovascular age-related macular degeneration patients.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1451726},
pmid = {39669991},
issn = {2296-858X},
abstract = {BACKGROUND: To evaluate factors affecting visual acuity prognosis in patients with neovascular age-related macular degeneration (nAMD) following anti-vascular endothelial growth factor (anti-VEGF) therapy via intravitreal injection and to identify baseline risk factors for subretinal fibrosis (SF).<br><br>METHODS: A retrospective study of 64 nAMD eyes treated with intravitreal anti-VEGF treatment over 12&#x2009;months of follow-up was conducted. Demographic and optical coherence tomography characteristics at baseline were recorded to explore the relevant factors affecting visual acuity outcome. Find baseline risk factors for SF development. The primary baseline measures included OCT qualitative and quantitative indicators, and optical coherence tomography angiography (OCTA) quantitative features.<br><br>RESULTS: BCVA (logMAR) at 12&#x2009;months was positively correlated with age (r&#x2009;=&#x2009;0.258, p&#x2009;=&#x2009;0.040), baseline BCVA (r&#x2009;=&#x2009;0.749, p&#x2009;<&#x2009;0.001), central macular thickness (CMT) (r&#x2009;=&#x2009;0.413, p&#x2009;<&#x2009;0.001), subretinal hyperreflective material (SHRM) (r&#x2009;=&#x2009;0.304, p&#x2009;=&#x2009;0.014), intraretinal fluid (IRF) (r&#x2009;=&#x2009;0.423, p&#x2009;<&#x2009;0.001), type 2 macular neovascularization (MNV) (r&#x2009;=&#x2009;0.272, p&#x2009;=&#x2009;0.029), and ellipsoidal zone breaks (r&#x2009;=&#x2009;0.299, p&#x2009;=&#x2009;0.016), and hyperreflective foci (HF) (r&#x2009;=&#x2009;0.264, p&#x2009;=&#x2009;0.035). Eyes with SF had worse baseline BCVA (p&#x2009;<&#x2009;0.001), greater CMT (p&#x2009;=&#x2009;0.009), and a higher prevalence of IRF (p&#x2009;=&#x2009;0.005), type 2 MNV (p&#x2009;=&#x2009;0.001), SHRM (p&#x2009;=&#x2009;0.012), and HF (p&#x2009;=&#x2009;0.028). Logistic binary regression analysis showed that baseline BCVA (logMAR) (OR&#x2009;=&#x2009;0.02, 95% CI: 0.00-0.45, p&#x2009;=&#x2009;0.013), HF (OR&#x2009;=&#x2009;0.11, 95% CI: 0.01-0.95, p&#x2009;=&#x2009;0.045), and type 2 MNV (OR&#x2009;=&#x2009;0.08, 95% CI: 0.01-0.88, p&#x2009;=&#x2009;0.039) were independent risk factors of subretinal fibrosis. As for quantitative OCTA parameters, eyes with subretinal fibrosis had a larger microvascular lesion size (p&#x2009;=&#x2009;0.003), larger vessels area (p&#x2009;=&#x2009;0.002), higher number of vessel junctions (p&#x2009;=&#x2009;0.042) and endpoints (p&#x2009;=&#x2009;0.024), longer total vessel length (p&#x2009;=&#x2009;0.005), and lower vessel length density (p&#x2009;=&#x2009;0.042).<br><br>CONCLUSION: This study enplores baseline OCT and OCTA characteristics associated with subretinal fibrosis in nAMD patients. This information can help predict the occurrence and progression of subretinal fibrosis, potentially leading to more personalized treatment approaches for nAMD patients.},
}
@article {pmid39667565,
year = {2025},
author = {Li, S and Su, D and Hu, S and Hu, Q and Sun, D},
title = {Epigallocatechin gallate ameliorates retinal pigment epithelial cell damage via the CYFIP2 /AKT pathway.},
journal = {Toxicology and applied pharmacology},
volume = {495},
number = {},
pages = {117124},
doi = {10.1016/j.taap.2024.117124},
pmid = {39667565},
issn = {1096-0333},
mesh = {*Catechin/analogs &amp; derivatives/pharmacology ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism ; Animals ; *Proto-Oncogene Proteins c-akt/metabolism ; Humans ; Apoptosis/drug effects ; Mice ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; *Macular Degeneration/pathology/drug therapy/prevention &amp; control ; Male ; Cell Line ; Hydrogen Peroxide/toxicity ; },
abstract = {Age-related macular degeneration (AMD) is a representative age-related ophthalmic disease, and the pathogenesis of AMD remains unclear. This research intended to determine whether epigallocatechin gallate (EGCG) could alleviate the progression of AMD and the possible mechanism. We constructed three groups of mice (young, aged, and EGCG), and HE and TUNEL staining of retinal tissues was performed to observe the structural changes in the retinal pigment epithelial (RPE) layer and the level of apoptosis, respectively. Through RNA-Sequencing analysis of retinal tissues and by RT-qPCR, GO, KEGG, and literature analyses, we identified cytoplasmic fragile X mental retardation 1-interacting protein 2 (CYFIP2) as a possible effector gene for EGCG action and validated its role by immunofluorescent and western blotting experiments. The CCK-8 and Hoechst 33342 apoptosis assays, and western blotting and qRT-PCR assays showed that EGCG reduced hydrogen peroxide (H2O2)-induced apoptosis in adult human RPE (ARPE-19) cells, and the expression of Cyfip2 was changed accordingly. RNA interference analysis indicated that Cyfip2 knockdown alleviated H2O2-induced ARPE apoptosis, while its overexpression weakened EGCG's protective effect. Western blot analysis showed that Cyfip2 mediated the anti-apoptotic effect of EGCG by modulating the level of protein kinase B (Akt) phosphorylation in ARPE cells, and the activation level of phosphorylated AKT (p-AKT Ser473) in retinal tissue of the EGCG-fed group was higher than that of the aged group. Taken together, this study suggests that EGCG plays a protective role in the development of AMD and the apoptosis of ARPE cells through the Cyfip2/AKT pathway.},
}
@article {pmid39667053,
year = {2025},
author = {Ahmed, W and Liatsis, P},
title = {LHU-VT: A Lightweight Hypercomplex U-Net with Vessel Thickness-Guided Dice Loss for retinal vessel segmentation.},
journal = {Computers in biology and medicine},
volume = {185},
number = {},
pages = {109470},
doi = {10.1016/j.compbiomed.2024.109470},
pmid = {39667053},
issn = {1879-0534},
mesh = {Humans ; *Retinal Vessels/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Algorithms ; },
abstract = {Vision loss is often caused by retinal disorders, such as age-related macular degeneration and diabetic retinopathy, where early indicators like microaneurysms and hemorrhages appear as changes in retinal blood vessels. Accurate segmentation of these vessels in retinal images is essential for early diagnosis. However, retinal vessel segmentation presents challenges due to complex vessel structures, low contrast, and dense branching patterns, which are further complicated in resource-limited settings requiring lightweight solutions. To address these challenges, we propose a novel Lightweight Hypercomplex U-Net[1] (LHUN) with Vessel Thickness-Guided Dice Loss (VTDL), collectively called LHU-VT. LHUN utilizes hypercomplex octonions to capture intricate patterns and cross-channel relationships in fundus images, reducing parameter count and enabling edge deployment. The VTDL component applies vessel thickness-guided weights to address class imbalance, thereby enhancing segmentation accuracy. Our experiments show that LHU-VT significantly outperforms current methods, achieving up to 2.4× fewer FLOPs, 4.4× fewer parameters, and 2.6× smaller model size. The model achieves AUC scores of 0.9938, 0.9879, 0.9988, and 0.9808, respectively, on four benchmark datasets CHASE, DRIVE, STARE, and HRF.},
}
@article {pmid39666349,
year = {2024},
author = {Williams, BL and Zouache, MA and Hageman, GS},
title = {Author Response: Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {26},
pmid = {39666349},
issn = {1552-5783},
}
@article {pmid39666348,
year = {2024},
author = {Pan, Y and Iwata, T},
title = {Letter to the Editor: Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {27},
pmid = {39666348},
issn = {1552-5783},
}
@article {pmid39663398,
year = {2025},
author = {Aziz, AA and Khanani, AM and Khan, H and Lauer, E and Khanani, I and Mojumder, O and Khanani, ZA and Khan, H and Gahn, GM and Graff, JT and Abbey, AM and Almeida, DRP and Barakat, MR and Corradetti, G and Graff, JM and Haug, SJ and Nielsen, JS and Sheth, VS and Sadda, SR and Hadas, I and Benyamini, G and Nahen, K and Mohan, N},
title = {Retinal fluid quantification using a novel deep learning algorithm in patients treated with faricimab in the TRUCKEE study.},
journal = {Eye (London, England)},
volume = {39},
number = {6},
pages = {1099-1106},
pmid = {39663398},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence/methods ; *Deep Learning ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Male ; Female ; *Subretinal Fluid/diagnostic imaging/metabolism ; Aged ; Intravitreal Injections ; *Algorithms ; *Wet Macular Degeneration/drug therapy/diagnosis/metabolism ; Aged, 80 and over ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: Investigate retinal fluid changes via a novel deep-learning algorithm in real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Multicenter, retrospective chart review and optical coherence tomography (OCT)&#xa0;image upload from participating sites was conducted on patients treated with faricimab for nAMD from February 2022 to January 2024. The Notal OCT Analyzer (NOA) algorithm provided intraretinal, subretinal and total retinal fluid for each scan. Results were segregated based on treatment history and fluid compartments, allowing for multiple cross-sections of evaluation.<br><br>RESULTS: A total of 521 eyes were included at baseline. The previous treatments prior to faricimab were aflibercept, ranibizumab, bevacizumab, or treatment-naive for 52.3%, 21.0%, 13.3%, and 11.2% of the eyes, respectively. Of all 521 eyes, 49.9% demonstrated fluid reduction after one injection of faricimab. The mean fluid reduction after one injection was -60.7nL. The proportion of eyes that saw reduction in fluid compared to baseline after second, third, fourth and fifth faricimab injections were 54.4%, 51.9%, 51.4% and 52.2%, respectively. The mean (SD) retreatment interval after second, third, fourth and fifth faricimab injection were 53.4 (34.3), 56.6 (36.0), 57.1 (35.3) and 61.5 (40.2) days, respectively.<br><br>CONCLUSION: Deep-learning algorithms provide a novel tool for evaluating precise quantification of retinal fluid after treatment of nAMD with faricimab. Faricimab demonstrates reduction of retinal fluid in multiple groups after just one injection and sustains this response after multiple treatments, along with providing increases in treatment intervals between subsequent injections.},
}
@article {pmid39662686,
year = {2025},
author = {Xue, CC and Li, H and Yu, M and Chong, CCY and Fan, Q and Tham, YC and Cheung, CMG and Wong, TY and Chew, EY and Cheng, CY},
title = {Omega-3 Fatty Acids as Protective Factors for Age-Related Macular Degeneration: Prospective Cohort and Mendelian Randomization Analyses.},
journal = {Ophthalmology},
volume = {132},
number = {5},
pages = {598-609},
pmid = {39662686},
issn = {1549-4713},
support = {ZIA EY000489/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; Prospective Studies ; Male ; Female ; Aged ; *Fatty Acids, Omega-3/blood ; *Docosahexaenoic Acids/blood ; *Macular Degeneration/genetics/epidemiology/blood/prevention &amp; control ; Genome-Wide Association Study ; Middle Aged ; Polymorphism, Single Nucleotide ; Incidence ; United Kingdom/epidemiology ; Complement Factor H/genetics ; Risk Factors ; Protective Factors ; },
abstract = {PURPOSE: Epidemiologic studies and clinical trials have reported inconsistent findings regarding omega-3 fatty acids' protective role in age-related macular degeneration (AMD). We investigated their association in a prospective cohort and examined causality using Mendelian randomization (MR) analyses.<br><br>DESIGN: Prospective cohort study and 2-sample MR analyses.<br><br>PARTICIPANTS: The cohort included 258 350 AMD-free individuals of European descent from the UK Biobank. Mendelian randomization analyses used genome-wide association study data on plasma omega-3 and docosahexaenoic acid (DHA) (UK Biobank, n&#xa0;= 115 006) and AMD (dry, wet, and any; FinnGen, n&#xa0;= 208 690-209 122).<br><br>METHODS: Cox regression assessed the association between plasma omega-3 and DHA levels and AMD incidence, adjusting for systemic covariates and AMD polygenetic risk score (PRS). Interaction effects of AMD genetic risk (PRS, complement factor H and age-related maculopathy susceptibility 2 genotypes), and plasma omega-3 and DHA levels were tested. For MR analyses, we used random-effect inverse-variance weighted model as primary, with 5 sensitivity models. Causality was considered significant if P < 0.05 in the primary model and at least 2 sensitivity models.<br><br>MAIN OUTCOME MEASURES: Risk of AMD.<br><br>RESULTS: Over 12.9 years, 5068 people (1.9%) demonstrated AMD. Higher plasma levels (in millimoles per liter) of omega-3 (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.72-0.95; P&#xa0;= 0.006) and DHA (HR, 0.65; 95% CI, 0.44-0.96; P&#xa0;= 0.029) were associated with lower risk of receiving an AMD diagnosis. Mendelian randomization showed genetic predisposition to higher plasma omega-3 levels reduced the risk of dry AMD (odds ratio [OR], 0.83; 95% CI, 0.73-0.96; P&#xa0;= 0.010), wet AMD (OR, 0.76; 95% CI, 0.65-0.88; P < 0.001), and any AMD (OR, 0.82; 95% CI, 0.74-0.92; P < 0.001). Similar results were found for plasma DHA levels (wet AMD:OR, 0.79; 95% CI, 0.65-0.96; P&#xa0;= 0.017; any AMD: OR, 0.84; 95% CI, 0.72-0.98; P&#xa0;= 0.030). No significant interaction was found between omega-3 and DHA levels and AMD genetic risk (all P > 0.05).<br><br>CONCLUSIONS: Both the prospective and MR analyses suggest omega-3 and DHA may protect against AMD, supporting the need for further clinical trials to test their effectiveness in AMD prevention and treatment.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39662591,
year = {2025},
author = {Alshaikhsalama, AM and Alsoudi, AF and Wai, KM and Koo, E and Mruthyunjaya, P and Rahimy, E},
title = {Association between Obstructive Sleep Apnea and Age-related Macular Degeneration Development and Progression.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {6},
pages = {537-545},
doi = {10.1016/j.oret.2024.12.004},
pmid = {39662591},
issn = {2468-6530},
mesh = {Humans ; *Sleep Apnea, Obstructive/complications/diagnosis ; Retrospective Studies ; Male ; Female ; Disease Progression ; Aged ; Follow-Up Studies ; Incidence ; Middle Aged ; Risk Factors ; Polysomnography ; *Macular Degeneration/etiology/diagnosis/epidemiology ; *Wet Macular Degeneration/diagnosis/etiology/epidemiology ; },
abstract = {OBJECTIVE: To evaluate the risk of age-related macular degeneration (AMD) development and progression in individuals with diagnosed obstructive sleep apnea (OSA).<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: Before propensity score matching (PSM), 60 652 and 1 173 723 individuals with OSA or not, respectively, were included in the study. After PSM and applying inclusion/exclusion criteria, 58 700 individuals in each cohort were subsequently analyzed.<br><br>METHODS: Data were collected using TriNetX, a deidentified electronic health records research network. Individuals with an International Classification of Diseases, 10th Revision, code for OSA confirmed with polysomnography and an additional code for continuous positive airway pressure use were compared with individuals without diagnosed OSA (control cohort) for the development of main outcome measures at 5 years. Secondary analyses were included to assess nonadvanced AMD progression in individuals with and without diagnosed OSA at 5 years.<br><br>MAIN OUTCOME MEASURES: The main outcome measures were the incidence of AMD, macular hemorrhage, legal blindness, and requiring anti-VEGF intervention at 5 years. Individuals with nonadvanced AMD with and without an OSA diagnosis were separately analyzed for progression to late AMD and the development of macular hemorrhage, legal blindness, and requiring anti-VEGF therapy at 5 years.<br><br>RESULTS: At 5 years, individuals with diagnosed OSA had a significantly elevated risk of nonexudative AMD (hazard ratio [HR], 2.64; 95% confidence interval [CI], 2.37-2.96; P < 0.001), exudative AMD (HR, 2.48; 95% CI, 1.99-3.11; P = 0.002), and requiring anti-VEGF therapy (HR, 2.85; 95% CI, 2.26-3.59; P < 0.001) compared with the control cohort. In the secondary analysis, individuals with nonadvanced AMD with diagnosed OSA were associated with an elevated risk of geographic atrophy (HR, 7.00; 95% CI, 4.47-11.0; P = 0.03), exudative AMD (HR, 2.87; 95% CI, 2.37-3.48; P = 0.03), and requiring anti-VEGF injections (HR, 4.72; 95% CI, 3.59-6.22; P = 0.02) compared with those with nonadvanced AMD without diagnosed OSA.<br><br>CONCLUSIONS: In a large, heterogeneous database, an elevated risk of developing AMD and progression to later stages of the disease was observed among individuals with diagnosed OSA.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39661945,
year = {2025},
author = {Romano, F and Ding, X and Garcia, M and Zhao, Y and Vingopoulos, F and Garg, I and Stettler, I and Bennett, C and Overbey, K and Finn, MJ and Ploumi, I and Laìns, I and Patel, NA and Wu, DM and Vavvas, DG and Husain, D and Miller, JW and Miller, JB},
title = {ASSESSING THE REPEATABILITY OF INNER CHOROID FLOW DEFICIT PERCENTAGE IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION AND CONTROLS: A Comparative Study Between Different Post-Processing Approaches.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {3},
pages = {454-463},
doi = {10.1097/IAE.0000000000004345},
pmid = {39661945},
issn = {1539-2864},
support = {R01 EY030088/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/blood supply/diagnostic imaging ; Cross-Sectional Studies ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Fluorescein Angiography/methods ; Reproducibility of Results ; Middle Aged ; Visual Acuity/physiology ; *Regional Blood Flow/physiology ; Aged, 80 and over ; Fundus Oculi ; *Macular Degeneration/physiopathology/diagnosis ; },
abstract = {PURPOSE: To assess repeatability of macular inner choroid flow deficit percentage in intermediate age-related macular degeneration and controls using various postprocessing approaches.<br><br>METHODS: Cross-sectional, observational study. The authors included 1) 22 intermediate age-related macular degeneration and 24 control eyes, with 2) age >50 years, 3) visual acuity >20/32, and 4) no additional ocular and systemic confounders. Participants underwent four consecutive 6 &#xd7; 6-mm optical coherence tomography angiography scans (2 acquired at 100-kHz and 2 at 200-kHz speed; PLEX Elite 9000) for intrasession analysis. Same protocol was repeated after 30 minutes for intersession analysis. Three slabs of different thicknesses were generated underneath Bruch membrane (4-14, 4-19, 4-24 &#xb5; m). All slabs were processed with: 1) binarization-only using Phansalkar method (r = 4-15 pixels); 2) compensation + binarization; 3) averaging + binarization; 4) averaging + compensation + binarization. Inner choroid flow deficit percentage was measured within 3-mm and 5-mm circles, and measurements were repeated after excluding drusen areas. Repeatability was analyzed with generalized linear mixed-effects models, intraclass correlation coefficients, and Levene variance test.<br><br>RESULTS: Most postprocessing approaches demonstrated high repeatability (intraclass correlation coefficient >0.75) with no significant test-retest differences (P > 0.05). Compensation + binarization of 15- &#xb5; m slabs at 200 kHz showed the highest repeatability (intraclass correlation coefficient: 0.96-0.98). Excluding drusen did not significantly affect inner choroid flow deficit percentage measurements (P > 0.05), showing increased intraclass correlation coefficients for 10-&#xb5;m-thick and binarized-only slabs.<br><br>CONCLUSION: Strong repeatability can be achieved with various postprocessing methods for assessing inner choroid flow deficit percentage, especially with compensation + binarization of 15- &#xb5; m slabs acquired at 200 kHz. Drusen removal does not seem to affect repeatability in intermediate age-related macular degeneration when using a swept-source device, except for specific settings. These results contribute to refining choriocapillaris assessment, paving the way for future applications.},
}
@article {pmid39660500,
year = {2025},
author = {Zhang, Y and Xu, X},
title = {Effects of miR-21/NLRP3 on Blue Light-Induced Retinal Neurodegeneration in Mice.},
journal = {Current eye research},
volume = {50},
number = {3},
pages = {295-303},
doi = {10.1080/02713683.2024.2419684},
pmid = {39660500},
issn = {1460-2202},
mesh = {Animals ; *MicroRNAs/genetics/biosynthesis ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/biosynthesis ; Mice ; *Retinal Degeneration/metabolism/etiology/genetics/pathology ; Disease Models, Animal ; Electroretinography ; *Light/adverse effects ; Mice, Inbred C57BL ; Blotting, Western ; Intravitreal Injections ; Apoptosis ; *Gene Expression Regulation/physiology ; Male ; In Situ Nick-End Labeling ; *Radiation Injuries, Experimental/metabolism ; *Retina/radiation effects ; Blue Light ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a chronic retinal disease that can lead to blindness. While the NLR family pyrin domain containing 3 (NLRP3) inflammasome is implicated in AMD, the specific roles of miR-21 and NLRP3 in AMD-related inflammation remain unclear. Therefore, this study aimed to investigate the roles of miR-21 and NLRP3 in blue light-induced neurodegeneration in the mouse retina.<br><br>METHODS: A mouse model of retinal light damage was established through three months of blue light exposure (BLE). The experimental groups comprised the Control (Ctrl), BLE, BLE&#x2009;+&#x2009;miR-nc, and BLE&#x2009;+&#x2009;miR-21 inhibitor groups. The microRNAs were administered via intravitreal injections once per week. After successful modeling, changes in visual function and retinal morphology were investigated by using electroretinography and hematoxylin and eosin staining, respectively. Photoreceptor apoptosis was assessed using the TdT-mediated dUTP nick-end labeling assay. Immunofluorescence was used to detect and locate microglia and NLRP3 expression in the mouse retina. The expression of miR-21, NLRP3, and downstream factors in the retinas of each group was measured using qRT-PCR and western blotting.<br><br>RESULTS: In the BLE and BLE&#x2009;+&#x2009;miR-nc groups, there was a decrease in visual function and retinal thickness, an increase in retinal ganglion cell injury and photoreceptor cell apoptosis, and elevated microglia activity in the retina, as evidenced by their migration to the outer retinal layer. In addition, the expression of miR-21, NLRP3, and downstream factors was increased in the BLE and BLE&#x2009;+&#x2009;miR-nc groups compared to that in the control group. However, intravitreal injection of the miR-21 inhibitor reduced miR-21 expression in the retina and significantly inhibited the activation of the NLRP3 inflammasome, effectively alleviating retinal photodamage caused by BLE.<br><br>CONCLUSIONS: This study indicates that miR-21 may mitigate blue-light-induced retinal neurodegeneration by reducing the activation of the NLRP3 inflammasome in the mouse retina.},
}
@article {pmid39654701,
year = {2024},
author = {Heier, JS and Liu, Y and Holekamp, NM and Ali, MH and Astafurov, K and Blinder, KJ and Busquets, MA and Chica, MA and Elman, MJ and Fein, JG and Hahn, P and London, N and Margolis, T and Modi, YS and Rachitskaya, A and Schneider, EW and Stoller, GL and Wang, JC and Shah, AR},
title = {Clinical Use of Home OCT Data to Manage Neovascular Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264241302858},
pmid = {39654701},
issn = {2474-1272},
abstract = {Purpose: To investigate how home optical coherence tomography (OCT) influences the clinical decision-making of retina specialists for the management of neovascular age-related macular degeneration (nAMD). Methods: In this retrospective imaging review, 15 retina specialists each evaluated 10 home OCT data segments from 29 eyes being treated for nAMD. Based on OCT data, indications were identified for when eyes should be treated, which antivascular endothelial growth factor should be used, and the specific retinal fluid and time thresholds for notification. Results: Withholding treatment was recommended in 64 (42.7%) of 150 data segments (95% CI, 34.7-50.6), whereas 100% of eyes received treatment on the last day of each data segment. Treatment was recommended in 86 cases (57.3%), with treatment occurring 7 or more days before the actual treatment was advised in 52 (60.5%) of 86 data segments. This earlier treatment would have prevented the accumulation of intraretinal fluid (IRF), subretinal fluid (SRF), and total retinal fluid for 69.1 nL, 162.2 nL, and 231.2 nL days. Retina specialists chose a different type of treatment agent in 35 (40%) of 86 cases. The following notification values were set: IRF, mean 9.8 ± 14.9 nL (median, 5; IQR, 5); SRF, mean 10.2 ± 16.1 nL (median, 5.5; IQR, 5); total retinal fluid, mean 15.2 ± 24.0 nL (median, 10; IQR, 5). The time-based notification interval was set at a mean of 34.7 ± 21.9 days (median, 30; IQR, 2). Conclusions: Home OCT-based decision-making by retina specialists differed substantially from actual clinical care. Home OCT has the potential to facilitate personalized care in nAMD.},
}
@article {pmid39654700,
year = {2024},
author = {Iftikhar, M and Hsu, ST and Vajzovic, L and Hadziahmetovic, M},
title = {Acute Submacular Hemorrhage Resulting from Neovascular Age-Related Macular Degeneration in a Monocular Patient.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264241305103},
pmid = {39654700},
issn = {2474-1272},
abstract = {Purpose: To present the management and outcomes of a case of acute submacular hemorrhage due to neovascular age-related macular degeneration (nAMD). Methods: A single case was retrospectively evaluated. Results: A 79-year-old man with a history of submacular hemorrhage from nAMD and persistent disease activity in the left eye presented with acute submacular hemorrhage in his better-seeing right eye, which was previously closely monitored for an extrafoveal serous pigment epithelial detachment without exudation. The patient received intravitreal antivascular endothelial growth factor (anti-VEGF) and subsequently had pars plana vitrectomy with subretinal tissue plasminogen activator and gas tamponade. After 5 days of face-down positioning, the hemorrhage was successfully displaced from the fovea. Recurrent disease activity 2 weeks postoperatively prompted intensive biweekly anti-VEGF therapy. By postoperative month 5, the patient's visual acuity improved from 20/400 to 20/70 OD. Conclusions: This case highlights the importance of close monitoring of patients with nAMD exhibiting aggressive disease as well as the efficacy of prompt surgical intervention and increased anti-VEGF frequency for large submacular hemorrhages.},
}
@article {pmid39654042,
year = {2024},
author = {Hillenmayer, A and Wertheimer, CM and Hillenmayer, M and Strehle, LD and Hartmann, LM and Vounotrypidis, E and Wolf, A},
title = {Comparison of different treatment options in submacular haemorrhage.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {525},
pmid = {39654042},
issn = {1471-2415},
mesh = {Humans ; Retrospective Studies ; *Vitrectomy/methods ; Male ; *Retinal Hemorrhage/surgery/therapy/diagnosis ; Female ; *Visual Acuity/physiology ; Aged ; Aged, 80 and over ; Tissue Plasminogen Activator/therapeutic use/administration &amp; dosage ; Middle Aged ; Fibrinolytic Agents/therapeutic use ; Follow-Up Studies ; Endotamponade/methods ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND/AIMS: Submacular haemorrhages (SMH) cause significant visual impairment. Until now, the comparative effectiveness of different treatment approaches remains inconclusive without clear treatment guidelines. The aim of our study was to evaluate the effectiveness of 5 surgical treatment modalities in terms of visual prognosis and success rate.<br><br>METHODS: This retrospective study included 201 patients with SMH. Primary endpoint was best corrected visual acuity (BCVA), secondary endpoints included haemorrhage size and complications. Group 1 was treated with pneumatic displacement and rtPA-injection. Group 2 followed the "Manchester protocol" with rtPA-injection and-if needed-a standardised secondary procedure with pars plana vitrectomy (ppV) and subretinal rtPA. Group 3 underwent vitrectomy with subretinal rtPA, group 4 vitrectomy only and group 5 received subretinal lavage.<br><br>RESULTS: Baseline characteristics were a mean age of 79&#xa0;years and a follow-up of 4.6&#xa0;months. Pre-intervention BCVA of 1.7 logMAR improved to 1.4 logMAR at follow-up. A gain of&#x2009;>&#x2009;0.2 logMAR was achieved in 47% of patients, while 20% lost&#x2009;>&#x2009;0.2 logMAR. Only group 2 achieved a statistically significant visual gain. While group 5 was statistically larger in haemorrhage size preoperatively (p&#x2009;<&#x2009;0.05), all groups were statistically equal in SMH size at follow-up. Complications led to additional interventions in 20% of patients.<br><br>CONCLUSIONS: No significant change in visual prognosis could be achieved depending on the intervention. As more invasive techniques seem to lack the benefit of a better postoperative prognosis while carrying higher risks, it may be beneficial considering a less invasive option first.},
}
@article {pmid39653244,
year = {2025},
author = {Tao, L and He, D and Chen, Y and Yang, K and He, B and Cai, P and Cai, B and Liao, C and Liu, Z and Li, S and Chen, J and Wu, Y},
title = {Transferrin ameliorates retinal degeneration by mediating the dimerization of all-trans-retinal.},
journal = {The Journal of biological chemistry},
volume = {301},
number = {1},
pages = {108054},
pmid = {39653244},
issn = {1083-351X},
mesh = {Animals ; Mice ; Retinal Pigment Epithelium/metabolism/pathology ; *Retinal Degeneration/metabolism/pathology/genetics ; *Retinaldehyde/metabolism/chemistry/analogs &amp; derivatives ; *Transferrin/metabolism/genetics ; Humans ; Dimerization ; Protein Multimerization ; Mice, Inbred C57BL ; Retinoids ; },
abstract = {High levels of all-trans-retinal (atRAL) in the retina is considered to be responsible for the development of autosomal recessive Stargardt's disease (STGD1) and dry age-related macular degeneration (dAMD). Two bisretinoids, all-trans-retinal dimer (atRAL-dimer) and N-retinyl-N-retinylidene ethanolamine (A2E), form from the dimerization of atRAL in the retina but they possess much lower toxicity and phototoxicity toward retinal pigment epithelium (RPE) cells than atRAL. Here, we introduced a novel function of transferrin (TRF) in mediating the conversion of atRAL into atRAL-dimer and A2E, which effectively protected the retina from damage by atRAL and prevented retinal function decline in mice, and rescued atRAL-loaded RPE cells. Moreover, TRF-mediated conversion of atRAL to atRAL-dimer and A2E required the help of bicarbonate ions (HCO3[-]). atRAL had the capacity to stimulate the expression of TRF in RPE and photoreceptor cells as well as RPE/choroid and neural retina of mice, reflecting that the elevation of TRF levels by atRAL is most likely to help defy level increase and cytotoxicity of atRAL through facilitating its dimerization and thereby serves as a mechanism of retinal self-protection. Our findings offer a promising avenue for the treatment of retinopathies characterized by disrupted clearance of atRAL.},
}
@article {pmid39652834,
year = {2025},
author = {Huang, RS and Patil, NS and Mihalache, A and Xie, J and Popovic, MM and Kertes, PJ and Muni, RH and Kohly, RP},
title = {SOCIAL DETERMINANTS OF HEALTH IN AGE-RELATED MACULAR DEGENERATION: A Nationally Representative Survey Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {4},
pages = {703-713},
doi = {10.1097/IAE.0000000000004356},
pmid = {39652834},
issn = {1539-2864},
mesh = {Humans ; Male ; Female ; Aged ; *Social Determinants of Health/statistics &amp; numerical data ; Middle Aged ; *Macular Degeneration/epidemiology ; Aged, 80 and over ; United States/epidemiology ; Health Surveys ; Prevalence ; Cross-Sectional Studies ; Risk Factors ; Self Report ; },
abstract = {PURPOSE: To investigate the relationship between social determinants of health and the prevalence of age-related macular degeneration (AMD).<br><br>METHODS: This analysis included adult respondents (&#x2265;50 years old) from the 2017 National Health Interview Survey. The primary outcomes were self-reported diagnosis of AMD and self-reported vision loss because of AMD. Univariable and multivariable logistic regression models were used for analysis.<br><br>RESULTS: A total of 14,267 National Health Interview Survey participants were included, of whom 668 (4.7%) reported an AMD diagnosis. In the multivariable analysis, respondents aged over 81 years had higher odds of AMD (odds ratio [OR] = 7.54, 95% confidence interval [CI], 4.76-11.96, P < 0.001) compared with those aged 50 to 60. Divorced, separated, or widowed participants (OR = 1.27, 95% CI, 1.01-1.61, P = 0.042) also had a higher odds of AMD compared with married participants. Conversely, Black/African-American (OR = 0.23, 95% CI, 0.14-0.39, P < 0.001), Asian (OR = 0.38, 95% CI, 0.16-0.88, P = 0.023), and gay, lesbian, or bisexual respondents (OR = 0.45, 95% CI, 0.22-0.93, P = 0.032) had lower odds of AMD compared with White and heterosexual respondents, respectively. Employment was also associated with lower odds of AMD (OR = 0.71, 95% CI, 0.53-0.96, P = 0.026) compared with unemployment.<br><br>CONCLUSION: Several social determinants of health were associated with self-reported AMD diagnosis. These factors should be considered by policymakers and clinicians to effectively orchestrate public health initiatives aimed at promoting equitable care.},
}
@article {pmid39650979,
year = {2024},
author = {Sourla, E and Blumenthal Yohai, M and Ismail, K},
title = {Assessing Clinicians' Documentation of Vision in Older Adults Who Presented With a Fall at the Accident and Emergency Department of Northampton General Hospital.},
journal = {Cureus},
volume = {16},
number = {11},
pages = {e73183},
pmid = {39650979},
issn = {2168-8184},
abstract = {Background Falls among elderly adults are one of the most common reasons that could lead to injury and modality, as vision is one of the modifiable risk factors for falls. By assessing it, we can detect those needing further follow-up with opticians or ophthalmologists, lowering the risk of falls secondary to poor vision. Methods Data were collected and reviewed retrospectively from a consecutive list of patients who presented with a fall or head injury to the Accident and Emergency Department at Northampton General Hospital. A total of 180 patients aged 75 years or older were randomly selected between November 2022 and January 2023. This audit measured the vision documentation in the vision assessment tool used in the Emergency Department at Northampton General Hospital and was based on the National Institute for Health and Clinical Excellence (NICE) and the Royal College of Physicians guidelines. Results Out of 180 patients in the sample, 34 (19%) had their visual assessments documented. Among them, around six (17.6%) out of 34 patients had a full vision assessment documenting all the sections in the vision assessment tool. Five (14.7%) out of 34 patients and 11 (32.3%) out of 34 patients did not have documentation about their distance and near vision, respectively. The visual fields were not documented in 22 (64.7%) out of 34 patients, and no assessment of the eye movements was reported in 16 (47%) out of 34 patients. Discussion Most of the patients in the Emergency Department lacked visual documentation, resulting in low compliance with the standards. One of the factors that contribute to elderly people's falling is low vision. Uncorrected refractive errors are one of the main causes of poor vision, but their correction is also associated with an increased risk of falls among elderly patients, as they require more time to adapt to changes in prescription (e.g., new glasses). In addition, patients who suffer from some eye conditions, such as glaucoma or macular degeneration, also have a high incidence of falls caused by an impairment of the visual fields. Conclusions All patients over 75 years old who presented with a fall to the Emergency Department should have a vision assessment. Vision documentation is essential to identify patients with vision impairment needing to receive an eye assessment after their discharge to reduce the risk of falls derived from poor vision. Strategies to improve this include training and the dissemination of information (for example, posters), which could help increase documentation rates.},
}
@article {pmid39648411,
year = {2025},
author = {D'Anna Mardero, O and Arruti Vázquez, N and Coca Robinot, JF and Peralta Calvo, J and Montaño, VE and Vallespín, E and Noval Martín, S},
title = {Review: Clinical findings and genetic characterization of children affected with X-linked retinoschisis in the Spanish population.},
journal = {European journal of ophthalmology},
volume = {35},
number = {3},
pages = {809-820},
doi = {10.1177/11206721241305244},
pmid = {39648411},
issn = {1724-6016},
mesh = {Humans ; *Retinoschisis/genetics/diagnosis/epidemiology ; Male ; Child ; *Eye Proteins/genetics ; Retrospective Studies ; Electroretinography ; Tomography, Optical Coherence ; Child, Preschool ; Female ; Spain/epidemiology ; Adolescent ; *Mutation ; Carbonic Anhydrase Inhibitors/therapeutic use ; Visual Acuity ; Acetazolamide/therapeutic use ; Genetic Testing ; Sulfonamides ; Thiazines ; },
abstract = {X-linked retinoschisis (XLRS) is an inherited retinal disorder due to mutations in retinoschisin 1, characterized by impaired central vision secondary to parafoveal cystic cavities and visual field loss by splitting through the retinal nerve fibre layer in the peripheral retina. It is the leading cause of juvenile macular degeneration in males, and currently there is no approved treatment but carbonic anhydrase inhibitors can be used. A retrospective review of the medical records of 17 children with confirmed XLRS seen in the Paediatric Ophthalmology Department of La Paz University Hospital from the 1st of January 2009 to the 1st of June of 2023 was conducted. Complete ophthalmological studies, genetic testing and full-field electroretinogram were performed. Topical brinzolamide was given to patients with foveoschisis, adding oral acetazolamide in those who did not improve with topical treatment alone or with very extensive foveoschisis at diagnosis. Surgical treatment was performed in retinal detahment (RD) or in no clearing hemovitreous cases. Mean age at diagnosis was 5,86 years and the most common reason for consultation was strabismus, followed by RD. The most frequently affected retinal later on Optic coherence tomography was the inner nuclear layer and throughout the follow-up we observed a decrease in central macular thickness. We found some genotype-phenotype correlation in our series and more severe phenotypes if the first amino acid of the protein is affected or in frameshift mutations. We found that medical treatment (topical and oral) improves foveoschisis, and that surgery shows poor outcomes, especially in younger patients.},
}
@article {pmid39643952,
year = {2025},
author = {Wei, MH and Li, JX and Mi, J and Wang, Q and Xu, F and Xu, C},
title = {Associations between co-exposure to multiple heavy metals and age-related macular degeneration: A cross-sectional study.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {87},
number = {},
pages = {127573},
doi = {10.1016/j.jtemb.2024.127573},
pmid = {39643952},
issn = {1878-3252},
mesh = {Humans ; *Macular Degeneration/chemically induced/urine ; *Metals, Heavy/urine/adverse effects ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; Aged ; Cadmium/urine ; *Environmental Exposure/adverse effects ; Nutrition Surveys ; Arsenic/urine ; },
abstract = {BACKGROUND &amp; AIMS: Accumulating evidence suggests that exposure to single heavy metal can facilitate the progression of age-related macular degeneration (AMD). However, the effects of exposure to mixtures of heavy metals on AMD remain largely unexplored. This study aims to investigate both the joint and individual impacts of arsenic (As), mercury (Hg), cadmium (Cd), and lead (Pb) on AMD within a co-exposure framework.<br><br>METHODS: Data from subjects participating the US National Health and Nutrition Examination Survey (NHANES, 2005-2008) were analyzed. Concentrations of As, Hg, Cd, and Pb were determined in urine by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS) for As and Hg, and inductively coupled plasma mass spectrometry (ICP-MS) for Cd and Pb. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed to assess the effects of heavy metal mixtures on AMD risk.<br><br>RESULTS: Both WQS and BKMR analyses consistently revealed a significant overall association between heavy metal mixtures and the risk of all types of AMD. The combined effect was more evident among patients with early AMD compared to those with late AMD. Cd and Hg were the main contributors driving these combined effects within the context of metal mixtures. Elevated urinary levels of Cd were positively correlated with an increased risk for all types as well as early AMD. Higher exposure to Hg corresponded with an elevated risk for early AMD. Furthermore, BKMR analysis indicated that the influence of Cd on early AMD exhibited a non-linear pattern.<br><br>CONCLUSIONS: Our findings suggest that co-exposure to As, Hg, Cd, and Pb is associated with an elevated risk for developing AMD, particularly in its early stages. Furthermore, excessive exposure to Cd and Hg has been identified as key contributing factors in this process.},
}
@article {pmid39643129,
year = {2025},
author = {Yang, B and Yang, K and Xi, R and Li, S and Chen, J and Wu, Y},
title = {Inhibition of JNK signaling attenuates photoreceptor ferroptosis caused by all-trans-retinal.},
journal = {Free radical biology &amp; medicine},
volume = {227},
number = {},
pages = {179-189},
doi = {10.1016/j.freeradbiomed.2024.12.007},
pmid = {39643129},
issn = {1873-4596},
mesh = {Animals ; *Ferroptosis/drug effects ; Mice ; Reactive Oxygen Species/metabolism ; *Retinaldehyde/metabolism ; Mice, Knockout ; Nuclear Receptor Coactivators/genetics/metabolism ; *Photoreceptor Cells, Vertebrate/metabolism/drug effects/pathology ; Humans ; MAP Kinase Signaling System/drug effects ; Ferritins/metabolism ; *Stargardt Disease/genetics/pathology/metabolism/drug therapy ; Retinal Degeneration/pathology/metabolism ; Lipid Peroxidation ; Mitogen-Activated Protein Kinase 8/genetics/metabolism/antagonists &amp; inhibitors ; Photoreceptor Cells/metabolism/drug effects ; Iron/metabolism ; Retina/metabolism/pathology/drug effects ; Mice, Inbred C57BL ; },
abstract = {The disruption of the visual cycle leads to the accumulation of all-trans-retinal (atRAL) in the retina, a hallmark of autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD), both of which cause retinal degeneration. Although our previous studies have shown that atRAL induces ferroptosis and activates c-Jun N-terminal kinase (JNK) signaling in the retina, the relationship between JNK signaling and ferroptosis in atRAL-mediated photoreceptor damage remains unclear. Here, we reported that JNK activation by atRAL drove photoreceptor ferroptosis through ferritinophagy. In photoreceptor cells loaded with atRAL, activated JNK phosphorylated c-Jun, which facilitated its nuclear translocation and promoted the expression of the nuclear receptor coactivator 4 (NCOA4). Elevated NCOA4 induced ferritin degradation via lysosomal processing, a process known as ferritinophagy, thereby releasing a large amount of labile iron. Iron overload led to the generation of reactive oxygen species (ROS) and lipid peroxidation, ultimately culminating in ferroptosis. Treatment with the JNK inhibitor JNK-IN-8, as well as the knockout of Jnk1 and Jnk2 genes, significantly rescued atRAL-loaded photoreceptor cells from ferritinophagy-induced ferroptosis. Abca4[-/-]Rdh8[-/-] mice, which exhibit atRAL accumulation in the retina following light exposure, are commonly used to study the pathological processes of STGD1 and dry AMD. In these mice, light exposure activated the JNK/c-Jun/NCOA4 axis, resulting in ferritinophagy in the neural retina. Importantly, intraperitoneal administration of JNK-IN-8 significantly rescued retinal function and photoreceptors from ferritinophagy-induced ferroptosis and effectively mitigated retinal degeneration in light-exposed Abca4[-/-]Rdh8[-/-] mice. This study underscores the critical role of the JNK/c-Jun/NCOA4 axis in mediating atRAL-induced ferritinophagy, which drives ferroptosis and retinal atrophy, suggesting that targeting this pathway may offer a potential therapeutic approach for STGD1 and dry AMD.},
}
@article {pmid39643072,
year = {2024},
author = {Tsiftsoglou, SA and Gavriilaki, E},
title = {A potential bimodal interplay between heme and complement factor H 402H in the deregulation of the complement alternative pathway by SARS-CoV-2.},
journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases},
volume = {126},
number = {},
pages = {105698},
doi = {10.1016/j.meegid.2024.105698},
pmid = {39643072},
issn = {1567-7257},
mesh = {Humans ; *Complement Factor H/metabolism/genetics ; *Complement Pathway, Alternative/genetics ; *COVID-19/immunology/virology/genetics ; *Heme/genetics/metabolism ; Polymorphism, Single Nucleotide ; *SARS-CoV-2/genetics/immunology ; *Spike Glycoprotein, Coronavirus/genetics/metabolism/immunology/chemistry ; },
abstract = {The recent discovery that the trimeric SARS-CoV-2 spike S glycoprotein carries heme within an NTD domain pocket of the S1 subunits, suggested that this virus may be cleverly utilizing heme, in addition to the S1 RBD domains, for invading target cells carrying a specific entry receptor like ACE2, TMEM106B and others. Studies during the COVID-19 pandemic revealed that the infectivity of this virus depends on cell surface heparan sulfate and that the infection induces non-canonical activation of the Complement Alternative pathway (AP) on the surface of infected cells. In our recent COVID-19 genomic studies, among the coding SNPs of interest we also detected the presence of the CFH rs1061170, rs800292 and rs1065489 within all the infected patient subgroups examined. The minor C allele of rs1061170 encodes CFH 402H that over the years has been associated with diseases characterized by complement dysregulation namely the age-related macular degeneration (AMD) and the atypical haemolytic uremic syndrome (aHUS). Also, more recently with the diminishment of CD4[+] T cell responses with ageing. The rs800292 minor allele A encodes CFH 62I that supports enhanced cofactor activity for Complement factor I (CFI). Also, the rs1065489 minor allele T encodes CFH 936D and is located within the CCP16 domain that influences the affinity of CFH with extracellular laminins. A subsequent computational analysis revealed that the CFH residue 402 is located centrally within a heme-binding motif (HBM) in domain CCP7 ([398]YNQNYGRKF[406]). Heme on the viral spike glycoprotein S1 subunit could recruit CFH 402H for masking free viral particles from opsonisation, and when in proximity to cell surface, act as a bait disrupting CFH 402H from the heparan sulphate coat of the target cells. Publicly available genetic data for European populations indicate that the minor C allele of rs1061170 is present only in haplotypes that carry the major alleles of rs800292 and rs1065489. This combination encodes for CFH 402H that exhibits increased biochemical affinity for heme in proximity, without enhanced cofactor activity for CFI and weaker association with the extracellular matrix. In the theatre of infection, this combination can promote heme-mediated viral infection with weaker complement opsonisation and potential AP deregulation. This strategy may be evolutionary conserved among various classes of infectious agents.},
}
@article {pmid39642914,
year = {2025},
author = {Son, KY and Choi, YJ and Kim, B and Han, K and Hwang, S and Jung, W and Shin, DW and Lim, DH},
title = {Association between Age-Related Macular Degeneration with Visual Disability and Risk of Dementia: A Nationwide Cohort Study.},
journal = {Journal of the American Medical Directors Association},
volume = {26},
number = {2},
pages = {105392},
doi = {10.1016/j.jamda.2024.105392},
pmid = {39642914},
issn = {1538-9375},
mesh = {Humans ; Male ; Female ; *Dementia/epidemiology ; *Macular Degeneration/complications/epidemiology ; Aged ; Republic of Korea/epidemiology ; Middle Aged ; *Vision Disorders/epidemiology ; Prospective Studies ; Cohort Studies ; Aged, 80 and over ; Risk Factors ; Proportional Hazards Models ; },
abstract = {OBJECTIVES: To investigate the prospective association between the risk of dementia and age-related macular degeneration (AMD) in patients with related visual disability (VD).<br><br>DESIGN: A nationwide population-based cohort study used authorized data provided by the Korean National Health Insurance Service.<br><br>SETTING AND PARTICIPANTS: A total of 1,788,457 individuals aged >50&#xa0;years who participated in the Korean National Health Screening Program were enrolled.<br><br>METHODS: From January 2009 to December 2019, participants were tracked for a diagnosis of dementia using registered diagnostic codes from claims data. Participants with VD were defined as those registered in a national disability registration established by the Korean government. The prospective association of AMD and related VD with new-onset dementia was investigated using a multivariate-adjusted Cox proportional hazard model adjusted for age, sex, body mass index, income level, systemic comorbidities, psychiatric diseases, and behavioral factors.<br><br>RESULTS: During the average follow-up period of 9.7 &#xb1; 2.16&#xa0;years, 4260 of 21,384 participants in the AMD cohort and 137,166 of 1,662,319 participants in the control cohort were newly diagnosed with dementia, respectively. Participants diagnosed with AMD showed a higher risk of new-onset dementia than those in the control group in the fully adjusted model [hazard ratio (HR) 1.11, 95% CI 1.07-1.14]. The risk of dementia was higher in participants diagnosed with AMD and associated VD (HR 1.28, 95% CI 1.15-1.43) compared to those without VD (HR 1.09, 95% CI 1.06-1.13).<br><br>CONCLUSIONS AND IMPLICATIONS: A diagnosis of AMD was associated with an increased risk of all-cause dementia and its major subtypes. Close monitoring of cognitive function in patients with AMD, especially those with VD, may help in early detection of all-cause dementia, which could reduce the socioeconomic burden and improve the quality of life of patients.},
}
@article {pmid39642690,
year = {2025},
author = {Beirão, S and Pereira, PMR and Fernandes, R and Tomé, JPC},
title = {Photosensitizer formulations in photodynamic therapy of age-related macular degeneration.},
journal = {European journal of medicinal chemistry},
volume = {283},
number = {},
pages = {117105},
doi = {10.1016/j.ejmech.2024.117105},
pmid = {39642690},
issn = {1768-3254},
mesh = {*Photochemotherapy ; *Macular Degeneration/drug therapy ; *Photosensitizing Agents/pharmacology/chemistry/therapeutic use ; Humans ; Animals ; Drug Compounding ; Molecular Structure ; },
abstract = {Age-related macular degeneration (AMD) is a progressive degenerative disease that leads to visual impairment, predominantly affecting the elderly. Despite significant advancements in treatment, a definitive cure remains elusive. Current therapeutic strategies only slow down disease progression, inhibiting abnormal blood vessels growth, and preserving or improving vision. Among these strategies, photodynamic therapy (PDT) has emerged as a promising treatment, particularly for neovascular form, the most severe form of the disease. Although several photosensitizers (PS) have been developed, only one has received clinical approval for use in AMD. This treatment involves the intravenous administration of a photosensitizing agent that preferentially accumulates in the abnormal blood vessels beneath the macula. Upon activation by targeted laser light, the PS triggers photochemical reactions, leading to vascular occlusion and the reduction of choroidal neovascularization. This review provides a comprehensive overview of both experimental and clinical studies on PDT for AMD, discussing the current state of research, challenges in treatment optimization, and potential future directions to enhance this therapeutic approach.},
}
@article {pmid39642572,
year = {2025},
author = {Fan, Q and Song, X and Li, M and Xu, Q and Yan, C and Li, H and Qu, Y},
title = {Neutrophils promote laser-induced choroidal neovascularization by increasing pro-inflammatory cytokines secretion and cell cycle arrest in retinal pigment epithelium.},
journal = {International immunopharmacology},
volume = {145},
number = {},
pages = {113735},
doi = {10.1016/j.intimp.2024.113735},
pmid = {39642572},
issn = {1878-1705},
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Choroidal Neovascularization/metabolism ; *Neutrophils/immunology ; Humans ; *Cytokines/metabolism ; *Mice, Inbred C57BL ; Cell Line ; Mice ; *Lasers/adverse effects ; Cell Cycle Checkpoints ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; MicroRNAs/metabolism/genetics ; Coculture Techniques ; Male ; },
abstract = {Inflammation is hypothesized to have essential functions in the development of wet age-related macular degeneration (AMD). Polymorphonuclear neutrophils (PMNs), recognized as major players in inflammation, are typically the first leukocytes to be recruited to an inflammatory site. Previous studies have identified neutrophil aggregates in the lesion site of the choroidal neovascularization model, and systemic depletion of neutrophils in adult mice is associated with reduced choroidal neovascularization (CNV) area, suggesting a pivotal role of PMNs in CNV pathogenesis. Here, we investigate the role of neutrophils in promoting CNV, a key feature of wet AMD. The malfunction and demise of retinal pigment epithelium cells are essential elements in CNV pathogenesis. Our hypothesis posits that neutrophils exacerbate CNV by influencing pro-inflammatory cytokines secreted by retinal pigment epithelium (RPE) cells. Using in vivo laser-induced CNV models with mice and in vitro experiments with the human ARPE-19 cell line, we demonstrated that co-culturing neutrophils with ARPE-19 cells induces an increase in pro-inflammatory cytokines and leads to S-phase cell cycle arrest, potentially through the induction of double-strand breaks (DSBs). Further exploration of this interaction revealed a potential pathway involving reactive oxygen species (ROS) and microRNA-23a, wherein PMNs induce DSBs by initiating the downregulation of LB1 via microRNA-23a. Additionally, we found that dHL-60 cell line could serve as a substitute for primary PMNs, highlighting its potential as a valuable tool in experimental models involving interactions with retinal cells. Our findings underscore the significant role of neutrophils in CNV pathogenesis, providing insights into potential therapeutic targets for wet AMD.},
}
@article {pmid39641966,
year = {2024},
author = {Cui, Y and Cui, J and Xue, CC and Mao, Y and Jonas, JB and Wang, YX and Chen, DN},
title = {Five-Year Incidence of Age-Related Macular Degeneration and Its Risk Factors in Adult Chinese Population: The Tongren Health Care Study.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {12},
pages = {10},
pmid = {39641966},
issn = {2164-2591},
mesh = {Humans ; Female ; Male ; *Macular Degeneration/epidemiology ; Incidence ; Middle Aged ; Risk Factors ; Aged ; China/epidemiology ; Adult ; Follow-Up Studies ; East Asian People ; },
abstract = {PURPOSE: To examine the 5-year incidence of age-related macular degeneration (AMD) and its associated factors in an adult Chinese population.<br><br>METHODS: The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital. Baseline examinations were performed from 2014 to 2015, with 5-year follow-up examinations conducted between 2019 and 2020. Fundus photographs were graded according to the Beckman Initiative guidelines.<br><br>RESULTS: A total of 5658 participants with gradable photographs at both examinations were included in the study, comprising 58.0% women, with a mean age of 54.9 &#xb1; 11.0&#xa0;years. The 5-year incidence of any, early, intermediate, and late AMD were 6.1% (95% confidence interval [CI], 5.5%-6.8%), 5.0% (95% CI, 4.4%-5.6%), 3.4% (95% CI, 2.9%-3.9%), and 0.3% (95% CI, 0.2%-0.4%), respectively. In multivariate analysis, incident early AMD was associated with older age (P < 0.001; odds ratio [OR], 1.04; 95% CI, 1.02-1.06), female sex (P = 0.011; OR, 1.42; 95% CI, 1.08-1.86), and a higher estimated glomerular filtration rate (P = 0.020; OR, 1.15; 95% CI, 1.02-1.30), whereas having diabetes was a protective factor (P = 0.019; OR, 0.61; 95% CI, 0.41-0.92). Incident intermediate AMD was associated with older age (P < 0.001; OR, 1.05; 95% CI, 1.04-1.07), a higher high-density lipoprotein cholesterol level (P < 0.001; OR, 1.97; 95% CI, 1.38-2.83) and a lower triglyceride level (P = 0.008; OR, 0.77; 95% CI, 0.64-0.93).<br><br>CONCLUSIONS: A higher estimated glomerular filtration rate level was a risk factor for incident early AMD. A higher high-density lipoprotein cholesterol level and lower triglyceride level were risk factors for incident intermediate AMD. This finding may point to the role of renal circulation and lipid metabolism in incident AMD.<br><br>TRANSLATIONAL RELEVANCE: This community-based longitudinal study may provide a valuable understanding of AMD and its associated factors for targeted prevention and management strategies.},
}
@article {pmid39641748,
year = {2024},
author = {Mulfaul, K and Khan, AH and Schwarte, SG and Voigt, AP and Moore, RF and Potempa, LA and Wang, K and Scheetz, TE and Stone, EM and Tucker, BA and Mullins, RF},
title = {Elevation of Granulocyte Colony Stimulating Factor in Human AMD Donor RPE-Choroid.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {15},
pmid = {39641748},
issn = {1552-5783},
support = {P30 EY025580/EY/NEI NIH HHS/United States ; R01 EY024605/EY/NEI NIH HHS/United States ; R01 EY033308/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism ; Female ; Male ; *Granulocyte Colony-Stimulating Factor/metabolism ; Aged ; *Macular Degeneration/metabolism ; *Enzyme-Linked Immunosorbent Assay ; Aged, 80 and over ; Tissue Donors ; Middle Aged ; },
abstract = {PURPOSE: Choroidal inflammation, complement deposition, and accumulation of C-reactive protein (CRP) are involved in age-related macular degeneration (AMD) pathology. The pro-inflammatory signals that regulate immune cell recruitment in the choroid of patients with AMD remain to be determined. We performed cytokine profiling of human AMD and age-matched control donor tissue to identify inflammatory molecules upregulated in AMD tissue.<br><br>METHODS: Protein was isolated from 25 AMD and 21 control donor RPE/choroid macular punches. Total protein was quantified, and 50 &#xb5;g assayed for expression of 40 cytokines using an inflammation array. We validated the elevated expression of granulocyte colony stimulating factor (G-CSF) protein by ELISA in a second cohort of 22 control and 26 AMD donors. To identify an AMD associated stressor responsible for upregulating G-CSF we assayed for changes in G-CSF protein secretion in RPE/choroid organ cultures treated with the monomeric (m)CRP, an inflammatory protein elevated in AMD.<br><br>RESULTS: Using a multiplex array, we identified elevated G-CSF protein in the choroid of AMD donors compared to age-matched non-AMD controls. Differential expression of G-CSF was confirmed via ELISA in an independent cohort of samples (P = 0.01). The mCRP, which is deposited in AMD choroids, increased G-CSF protein secretion in RPE/choroid organ cultures. Single nuclei RNA sequencing identified choroidal endothelial cells and fibroblasts as the primary cell types responsible for increased G-CSF secretion in response to mCRP. The G-CSF receptor is expressed primarily by choroidal macrophages and dendritic cells and anti-G-CSFR colocalizes with anti-CD45 and anti-CD68 in human donor choroid tissue.<br><br>CONCLUSIONS: Elevated G-CSF expression in AMD donor tissue as a result of increased levels of mCRP may be involved in immune cell recruitment in AMD contributing to inflammatory stress in the choroid.},
}
@article {pmid39641650,
year = {2024},
author = {Ciulla, TA and Cunningham, ET},
title = {Suprachoroidal drug delivery: a versatile therapeutic platform.},
journal = {Expert opinion on drug delivery},
volume = {21},
number = {12},
pages = {1705-1713},
doi = {10.1080/17425247.2024.2435461},
pmid = {39641650},
issn = {1744-7593},
}
@article {pmid39641479,
year = {2024},
author = {Sripunya, A and Chittasupho, C and Mangmool, S and Angerhofer, A and Imaram, W},
title = {Gallic Acid-Encapsulated PAMAM Dendrimers as an Antioxidant Delivery System for Controlled Release and Reduced Cytotoxicity against ARPE-19 Cells.},
journal = {Bioconjugate chemistry},
volume = {35},
number = {12},
pages = {1959-1969},
pmid = {39641479},
issn = {1520-4812},
mesh = {*Dendrimers/chemistry ; Humans ; *Gallic Acid/chemistry/pharmacology ; *Antioxidants/pharmacology/chemistry ; Cell Line ; *Cell Survival/drug effects ; Delayed-Action Preparations/chemistry ; Retinal Pigment Epithelium/drug effects/metabolism/cytology ; Drug Carriers/chemistry ; },
abstract = {Poly(amidoamine) (PAMAM) dendrimers have gained significant attention in various research fields, particularly in medicinal compound delivery. Their versatility lies in their ability to conjugate with functional molecules on their surfaces and encapsulate small molecules, making them suitable for diverse applications. Gallic acid is a potent antioxidant compound that has garnered considerable interest in recent years. Our research aims to investigate if the gallic acid-encapsulated PAMAM dendrimer generations 4 (G4(OH)-Ga) and 5 (G5(OH)-Ga) could enhance radical scavenging, which could potentially slow down the progression of age-related macular degeneration (AMD). Encapsulation of gallic acid in PAMAM dendrimers is a feasible alternative to prevent its degradation and toxicity. In vitro investigation of antioxidant activity was carried out using the DPPH and ABTS radical scavenging assays, as well as the FRAP assay. The IC50 values for DPPH and ABTS assays were determined through nonlinear dose-response curves, correlating the inhibition percentage with the concentration (μg/mL) of the sample and the concentration (μM) of gallic acid within each sample. G4(OH)-Ga and G5(OH)-Ga possess significant antioxidant activities as determined by the DPPH, ABTS, and FRAP assays. Moreover, gallic acid-encapsulated PAMAM dendrimers inhibit H2O2-induced reactive oxygen species (ROS) production in the human retinal pigment epithelium ARPE-19 cells, thereby improving antioxidant characteristics and potentially retarding AMD progression caused by ROS. In an evaluation of cell viability of ARPE-19 cells using the MTT assay, G4(OH)-Ga was found to reduce cytotoxic effects on ARPE-19 cells.},
}
@article {pmid39640589,
year = {2024},
author = {Xue, CC and Teo, KYC and Tham, YC and Li, H and Thakur, S and Sabanayagam, C and Fan, Q and Silver, DL and Wang, X and Cheung, CMG and Wong, TY and Chakravarthy, U and Cheng, CY and Nusinovici, S},
title = {Lipid-lowering drug and complement factor H genotyping-personalized treatment strategy for age-related macular degeneration.},
journal = {iScience},
volume = {27},
number = {12},
pages = {111344},
pmid = {39640589},
issn = {2589-0042},
abstract = {We investigated whether the effect of lipid-lowering drugs (LLDs) on age-related macular degeneration (AMD) differs according to the main complement genetic variants in Singapore Epidemiology of Eye Diseases (SEED) (n = 5,579) and UK Biobank studies (n = 445,727). The effect of LLD was determined for each stratum of 20 complement genetic variants. In SEED, 484 individuals developed AMD and 216 showed progression over 6 years. In the UK Biobank, 913 participants developed AMD over 11 years. rs1061170 variant (complement factor H gene) was the only variant for which we found a protective effect in both populations. This effect was found in individuals carrying at least one C allele in SEED (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.19-0.87) and in individuals carrying two C alleles in UK Biobank (hazard ratio [HR] = 0.65; 95% CI, 0.45-0.93). These effects corresponded to a 50% and 35% decrease in AMD risk, respectively. Our study highlights the potential for personalized therapy for AMD based on complement genotyping.},
}
@article {pmid39640234,
year = {2024},
author = {Carleton, M and Oesch, NW},
title = {Bridging the gap of vision restoration.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1502473},
pmid = {39640234},
issn = {1662-5102},
abstract = {Retinitis pigmentosa (RP) and Age-Related Macular Degeneration (AMD) are similar in that both result in photoreceptor degeneration leading to permanent progressive vision loss. This affords the possibility of implementing vision restoration techniques, where light signaling is restored to spared retinal circuitry to recreate vision. There are far more AMD patients (Wong et al., 2014), yet more resources have been put towards researching and developing vision restoration strategies for RP despite it rarity, because of the tractability of RP disease models. The hope is that these therapies will extend to the AMD population, however, many questions remain about how the implementation of prosthetic or optogenetic vision restoration technologies will translate between RP and AMD patients. In this review, we discuss the difference and similarities of RP and AMD with a focus on aspects expected to impact vision restoration strategies, and we identify key gaps in knowledge needed to further improve vision restoration technologies for a broad patient population.},
}
@article {pmid39639888,
year = {2025},
author = {Panda-Jonas, S and Jonas, RA and Xu, J and Wang, YX and Jonas, JB},
title = {Intraretinal Retinal Pigment Epithelium Cells in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {2},
pages = {100626},
pmid = {39639888},
issn = {2666-9145},
abstract = {PURPOSE: To examine intraretinally migrated retinal pigment epithelium cells (iRPECs) in enucleated human eyes with various retinal conditions and corresponding intraretinal hyperreflective bodies (iHRBs) in a large cohort of patients with age-related macular degeneration (AMD) in China.<br><br>DESIGN: Population-based study and histomorphometric investigation.<br><br>PARTICIPANTS: Participants of the population-based Beijing Eye Study and enucleated human eyes.<br><br>METHODS: OCT-based and fundus photography-based examination of the macula of the Beijing Eye Study participants and light-microscopical histomorphometry of enucleated human eyes.<br><br>MAIN OUTCOME MEASURES: Presence and location of iRPECs and iHRBs.<br><br>RESULTS: In the Beijing Eye Study (6551 eyes; 3301 participants), the prevalence of intermediate AMD and late AMD was 331 (5.1%) and 44 (0.6%), respectively. All 42 eyes with intermediate AMD and macular hyperpigmentation had iHRBs at locations corresponding spatially with macular hyperpigmentation on the fundus photographs. Among all eyes with intermediate AMD (n&#xa0;= 331), iHRBs were detected in 262 (79.2%) eyes. The most internal location of the iHRBs was at the ellipsoid zone in 46 (13.9%) eyes, at the external limiting membrane (ELM) in 45 (13.6%) eyes, and in the outer nuclear layer in 145 (43.8%) eyes. Out of the 262 eyes with iHRBs, 186 (71.0%) eyes showed a corresponding defect in the ellipsoid zone, and 128 (48.9%) eyes showed a defect in the ELM. The eyes with an iHRB located beneath the ELM did not show an ELM defect. The iHRBs were associated with a plume-like appearance and with a smoke-like appearance in 20 (7.6%) eyes and 137 (52.3%) eyes, respectively. All iHRBs did not have a shadow on the OCT images. Similar findings were obtained in the eyes with late AMD. Among 237 eyes examined histologically, 21 globes showed iRPECs: 8 eyes in parapapillary &#x3b1; zone/&#x3b2; zone; 5 eyes with myopic patchy atrophies, and 3 eyes with AMD. The iRPECs were spatially associated with an ELM defect and were not surrounded by a basal membrane.<br><br>CONCLUSIONS: Intraretinal hyperreflective bodies can be found in 3 out of 4 eyes with intermediate AMD, correlate histologically with intraretinally located (migrated) retinal pigment epithelium cells, and correspond spatially with localized defects of the ellipsoid zone and ELM.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39639246,
year = {2024},
author = {Karamat, MI and Saleem, H and Khakwani, M and Ahmed, A},
title = {Bilateral improvement in age-related macular degeneration following unilateral Aflibercept injection.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {523},
pmid = {39639246},
issn = {1471-2415},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use ; Male ; Middle Aged ; *Intravitreal Injections ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; },
abstract = {BACKGROUND: The "fellow-eye effect" in anti-vascular endothelial growth factor (anti-VEGF) therapy is a rare phenomenon, particularly with aflibercept. This case report documents the first instance of this effect in Pakistan, highlighting its significance in a resource-limited setting where recent regulatory changes have restricted treatment options for age-related macular degeneration (AMD).<br><br>CASE PRESENTATION: A 62-year-old male presented with bilateral central vision loss due to neovascular AMD. Optical Coherence Tomography revealed serous subretinal fluid in both eyes. Due to financial constraints, only the right eye received a single 2 mg intravitreal aflibercept injection. Remarkably, at the four-week follow-up, both eyes showed significant improvement. Visual acuity improved from 6/12 to 6/9 in the treated right eye and from 6/15 to 6/12 in the untreated left eye. OCT scans demonstrated bilateral resorption of subretinal fluid. At three months, complete fluid resorption was observed in both eyes, with visual acuity improving to 6/6 bilaterally.<br><br>CONCLUSIONS: This case underscores the potential of the "fellow-eye effect" in anti-VEGF therapy, particularly with aflibercept, in treating bilateral AMD. It highlights a possible strategy for optimizing treatment regimens and reducing costs in resource-limited settings. However, it also raises concerns about systemic absorption and potential risks. The findings emphasize the need for further research on the pharmacokinetics of anti-VEGF agents, personalized treatment plans, and alternative therapies. This case is particularly significant in the context of Pakistan's recent ban on bevacizumab, underscoring the urgent need for accessible and affordable AMD treatments in developing countries.},
}
@article {pmid39639153,
year = {2025},
author = {Chong, V},
title = {Edridge Green Lecture 2022-demystifying clinical trials and regulatory approvals in drug development.},
journal = {Eye (London, England)},
volume = {39},
number = {3},
pages = {484-487},
pmid = {39639153},
issn = {1476-5454},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Clinical Trials as Topic ; *Drug Approval ; *Drug Development ; Macular Degeneration/drug therapy/physiopathology ; Retinal Diseases/drug therapy ; United States ; *United States Food and Drug Administration ; },
abstract = {This article provides a comprehensive overview of clinical trial design and regulatory pathways essential for drug development, specifically in the context of retinal diseases. Key concepts include trial structure, efficacy and safety endpoints, and regulatory expectations from agencies like the FDA. It delves into recent regulatory advancements, such as the inclusion of low-luminance vision as a secondary endpoint and analyses case studies from age-related macular degeneration (AMD) trials. Approvals for key retinal drugs, such as ranibizumab and aflibercept, treatments for AMD and diabetic macular oedema, are discussed highlighting criteria like the 15-letter gain/loss in visual acuity as approvable/clinical meaningful efficacy endpoints. Insights into geographic atrophy (GA) and diabetic retinopathy trials showcase the evolving landscape, where anatomical endpoints and new drugs bring fresh challenges and opportunities. It also emphasizes the importance of academic-industry collaboration, citing instances of gene therapy development and innovative endpoint measures like the Multi-Luminance Mobility Test for retinal dystrophies. The overarching aim of this lecture was to demystify the process that spans the design of clinical trials to regulatory approval of drugs so that clinicians understand these complexities. In particular, it is important to understand the reasons behind selection of trial design, inclusion and exclusion criteria, primary and secondary efficacy endpoints and safety endpoints. Since this lecture, there have been important changes in this field including new guidance from the Food and Drug Administration (FDA) as well as lessons learnt from recent drug approvals that are included in this manuscript.},
}
@article {pmid39638278,
year = {2025},
author = {Ebner, LJA and Karademir, D and Nötzli, S and Wögenstein, GM and Samardzija, M and Grimm, C},
title = {Oxygen-dependent alternative mRNA splicing and a cone-specific motor protein revealed by single-cell RNA sequencing in hypoxic retinas.},
journal = {Experimental eye research},
volume = {251},
number = {},
pages = {110190},
doi = {10.1016/j.exer.2024.110190},
pmid = {39638278},
issn = {1096-0007},
mesh = {Animals ; Mice ; *Alternative Splicing ; Mice, Inbred C57BL ; *Hypoxia/genetics/metabolism ; *Kinesins/genetics/metabolism ; *RNA, Messenger/genetics ; *Retinal Cone Photoreceptor Cells/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; *Oxygen/metabolism ; RNA-Binding Proteins/genetics ; Gene Expression Regulation ; },
abstract = {Restricted oxygen supply in the aging eye may lead to hypoxic conditions in the outer retina and contribute not only to physiological aging but also to nonhereditary degenerative retinal diseases. To understand the hypoxic response of specific retinal cell types, we performed single-cell RNA sequencing of retinas isolated from mice exposed to hypoxia. Significantly upregulated expression of marker genes in hypoxic clusters confirmed a general transcriptional response to hypoxia. By focusing on the hypoxic response in photoreceptors, we identified and confirmed a kinesin motor protein (Kif4) that was specifically and strongly induced in hypoxic cones. In contrast, RNA-binding proteins Rbm3 and Cirbp were differentially expressed across clusters but demonstrated isoform switching in hypoxia. The resulting short variants of these gene transcripts are connected to epitranscriptomic regulation, a notion supported by the differential expression of writers, readers and erasers of m[6]A RNA methylations in the hypoxic retina. Our data indicate that retinal cells adapt to hypoxic conditions by adjusting their transcriptome at various levels including gene expression, alternative splicing and the epitranscriptome. Adaptational processes may be cell-type specific as exemplified by the cone-specific upregulation of Kif4 or general like alternative splicing of RNA binding proteins.},
}
@article {pmid39637413,
year = {2025},
author = {McReynolds, AJ and Patnaik, JL and Auer, EA and Lynch, AM},
title = {Loss to Follow-Up in Intermediate Age-Related Macular Degeneration Patients Enrolled in the University of Colorado AMD Registry.},
journal = {Ophthalmic epidemiology},
volume = {32},
number = {4},
pages = {443-445},
doi = {10.1080/09286586.2024.2428193},
pmid = {39637413},
issn = {1744-5086},
}
@article {pmid39636945,
year = {2024},
author = {Park, SH and Chey, JH and Heo, J and Han, KE and Park, SW and Byon, I and Kwon, HJ},
title = {Diagnostic ability of confocal scanning ophthalmoscope for the detection of concurrent retinal disease in eyes with asteroid hyalosis.},
journal = {PloS one},
volume = {19},
number = {12},
pages = {e0306091},
pmid = {39636945},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; Aged ; Middle Aged ; *Retinal Diseases/diagnosis/diagnostic imaging ; Retrospective Studies ; Ophthalmoscopes ; Microscopy, Confocal/methods/instrumentation ; Eye Diseases/diagnosis/diagnostic imaging ; Aged, 80 and over ; Vitreous Body/pathology/diagnostic imaging ; Ophthalmoscopy/methods ; Adult ; },
abstract = {PURPOSE: To compare the diagnostic capacity of a color fundus camera (CFC), ultra-wide-field bicolor confocal scanning laser ophthalmoscope (BC-cSLO; OPTOS), and true-color confocal scanning ophthalmoscope (TC-cSO; EIDON) in detecting coexisting retinal diseases in eyes with asteroid hyalosis (AH).<br><br>METHODS: The medical records of consecutive patients with AH who were referred to a tertiary hospital for subsequent assessment by a vitreoretinal specialist were retrospectively reviewed. Fundus images obtained simultaneously using CFC, BC-cSLO, and TC-cSO were classified into four grades based on their obscuration by asteroid bodies. The proportion of Grade 1 images (minimal obscuration group) was assessed for each imaging modality. The diagnostic and screening abilities for concurrent retinal diseases were compared in terms of the accuracy and sensitivity of each device.<br><br>RESULTS: Among the 100 eyes with AH, 76 had coexisting retinal diseases, such as diabetic retinopathy (DR), retinal vascular occlusion, age-related macular degeneration, epiretinal membrane, and retinitis pigmentosa. TC-cSO had the highest ratio of Grade 1 images (94%, P<0.001), followed by CFC (67%) and BC-cSLO (63%). CFC and BC-cSLO exhibited a 5.3-fold higher rate of significant obscuration than TC-cSO (P<0.001, 95% confidence intervals = 2.4~11.6 folds). TC-cSO demonstrated the highest accuracy and sensitivity (95% and 81%, respectively) compared with CFC (89% and 43%, respectively) and BC-cSLO (89% and 39%, respectively) for all retinal diseases. BC-cSLO showed the best performance for DR diagnosis.<br><br>CONCLUSIONS: TC-cSO images showed minimal obscuration and a superior ability for diagnosing retinal diseases accompanied by AH over other imaging devices. TC-cSO can be a valuable alternative screening tool for detecting retinal diseases when AH impedes fundus imaging.},
}
@article {pmid39635529,
year = {2024},
author = {Alic, L and Dendinovic, K and Papac-Milicevic, N},
title = {The complement system in lipid-mediated pathologies.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1511886},
pmid = {39635529},
issn = {1664-3224},
mesh = {Humans ; *Complement System Proteins/immunology/metabolism ; *Lipid Metabolism ; Animals ; *Immunity, Innate ; *Complement Activation/immunology ; Homeostasis/immunology ; },
abstract = {The complement system, a coordinator and facilitator of the innate immune response, plays an essential role in maintaining host homeostasis. It promotes clearance of pathogen- and danger-associated molecular patterns, regulates adaptive immunity, and can modify various metabolic processes such as energy expenditure, lipid metabolism, and glucose homeostasis. In this review, we will focus on the intricate interplay between complement components and lipid metabolism. More precisely, we will display how alterations in the activation and regulation of the complement system affect pathological outcome in lipid-associated diseases, such as atherosclerosis, obesity, metabolic syndrome, age-related macular degeneration, and metabolic dysfunction-associated steatotic liver disease. In addition to that, we will present and evaluate underlying complement-mediated physiological mechanisms, observed both in vitro and in vivo. Our manuscript will demonstrate the clinical significance of the complement system as a bridging figure between innate immunity and lipid homeostasis.},
}
@article {pmid39635018,
year = {2024},
author = {Choi, JY and Han, E and Yoo, TK},
title = {Application of ChatGPT-4 to oculomics: a cost-effective osteoporosis risk assessment to enhance management as a proof-of-principles model in 3PM.},
journal = {The EPMA journal},
volume = {15},
number = {4},
pages = {659-676},
pmid = {39635018},
issn = {1878-5077},
abstract = {BACKGROUND: Oculomics is an emerging medical field that focuses on the study of the eye to detect and understand systemic diseases. ChatGPT-4 is a highly advanced AI model with multimodal capabilities, allowing it to process text and statistical data. Osteoporosis is a chronic condition presenting asymptomatically but leading to fractures if untreated. Current diagnostic methods like dual X-ray absorptiometry (DXA) are costly and involve radiation exposure. This study aims to develop a cost-effective osteoporosis risk prediction tool using ophthalmological data and ChatGPT-4 based on oculomics, aligning with predictive, preventive, and personalized medicine (3PM) principles.<br><br>We hypothesize that leveraging ophthalmological data (oculomics) combined with AI-driven regression models developed by ChatGPT-4 can significantly improve the predictive accuracy for osteoporosis risk. This integration will facilitate earlier detection, enable more effective preventive strategies, and support personalized treatment plans tailored to individual patients. We utilized DXA and ophthalmological data from the Korea National Health and Nutrition Examination Survey to develop and validate osteopenia and osteoporosis prediction models. Ophthalmological and demographic data were integrated into logistic regression analyses, facilitated by ChatGPT-4, to create prediction formulas. These models were then converted into calculator software through automated coding by ChatGPT-4.<br><br>RESULTS: ChatGPT-4 automatically developed prediction models based on key predictors of osteoporosis and osteopenia included age, gender, weight, and specific ophthalmological conditions such as cataracts and early age-related macular degeneration, and successfully implemented a risk calculator tool. The oculomics-based models outperformed traditional methods, with area under the curve of the receiver operating characteristic values of 0.785 for osteopenia and 0.866 for osteoporosis in the validation set. The calculator demonstrated high sensitivity and specificity, providing a reliable tool for early osteoporosis screening.<br><br>This study illustrates the value of integrating ophthalmological data into multi-level diagnostics for osteoporosis, significantly improving the accuracy of health risk assessment and the identification of at-risk individuals. Aligned with the principles of 3PM, this approach fosters earlier detection and enables the development of individualized patient profiles, facilitating personalized and targeted treatment strategies. This study also highlights the potential of AI, specifically ChatGPT-4, in developing accessible, cost-effective, and radiation-free screening tools for advancing 3PM in clinical practice. Our findings emphasize the importance of a holistic approach, incorporating comprehensive health indices and interdisciplinary collaboration, to deliver personalized management plans. Preventive strategies should focus on lifestyle modifications and targeted interventions to enhance bone health, thereby preventing the progression of osteoporosis and contributing to overall patient well-being.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00378-0.},
}
@article {pmid39634790,
year = {2024},
author = {Shim, J and Kim, Y and Bak, J and Shin, S and Lee, K and Hwang, YH and Kong, HY and Han, JS},
title = {Preclinical evaluation of NG101, a potential AAV gene therapy for wet age-related macular degeneration.},
journal = {Molecular therapy. Methods &amp; clinical development},
volume = {32},
number = {4},
pages = {101366},
pmid = {39634790},
issn = {2329-0501},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in individuals over the age of 55. Approximately 10%-15% of AMD patients develop choroidal neovascularization (CNV), leading to wet AMD (wAMD), which accounts for nearly 90% of AMD-related blindness. Inhibition of vascular endothelial growth factor (VEGF) is the standard treatment for wAMD. However, the frequent administration of the current treatment imposes a significant burden on wAMD patients. Therefore, there is an unmet need for treatments that require less-frequent administration. Here, we present findings on the safety and efficacy of NG101, a recombinant adeno-associated virus (rAAV) vector encoding aflibercept, an anti-VEGF agent, for wAMD therapy. A single subretinal injection of NG101 effectively reduced CNV lesion leakage and size at doses as low as 1 × 10[6] in mouse and 3 × 10[9] viral genomes per eye in cynomolgus monkeys. In cynomolgus monkeys, NG101-derived aflibercept expression in ocular tissues persisted for 1 year post-injection, indicating sustained therapeutic potential. Biodistribution analysis revealed that NG101 was primarily localized in ocular tissues. Only mild and transient ocular inflammatory responses were observed. Overall, these findings suggest that NG101, with its efficacy at low doses and sustained expression, is a promising therapeutic candidate for wAMD.},
}
@article {pmid39632019,
year = {2024},
author = {Feo, A and Sarraf, D},
title = {Fluid Pathways in Age-Related Macular Degeneration Elucidated with Advanced Retinal Imaging.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {12},
pages = {1115-1117},
doi = {10.1016/j.oret.2024.08.019},
pmid = {39632019},
issn = {2468-6530},
}
@article {pmid39632002,
year = {2024},
author = {Xin, C and Liu, L},
title = {Impact of 25-hydroxyvitamin D and calcium on risk of age-related macular degeneration.},
journal = {The American journal of clinical nutrition},
volume = {120},
number = {6},
pages = {1461-1462},
doi = {10.1016/j.ajcnut.2024.09.030},
pmid = {39632002},
issn = {1938-3207},
}
@article {pmid39631526,
year = {2025},
author = {Prikalkhoran, S and Guiliano, D and Khalili, H},
title = {Storage stability and solution binding affinity of an Fc-fusion mimetic.},
journal = {Journal of pharmaceutical sciences},
volume = {114},
number = {2},
pages = {1061-1067},
doi = {10.1016/j.xphs.2024.11.016},
pmid = {39631526},
issn = {1520-6017},
mesh = {*Recombinant Fusion Proteins/chemistry/metabolism ; Drug Stability ; *Receptors, Vascular Endothelial Growth Factor/chemistry/metabolism ; *Immunoglobulin Fc Fragments/chemistry/metabolism ; Humans ; Vascular Endothelial Growth Factor A/metabolism ; Protein Binding ; Drug Storage ; *Receptors, Fc/chemistry/metabolism ; Solutions ; Polyethylene Glycols/chemistry ; },
abstract = {This study evaluates the storage stability and solution binding affinity of a novel Fc-fusion mimetic, receptor-PEG-receptor (RpR), designed to address limitations of the current therapeutic aflibercept, a gold-standard therapy for age-macular degeneration (AMD). Using di(bis-sulfone) PEG linker as a structural scaffold, the mimetic aims to improve the storage stability and binding efficacy of the Fc fusion protein. Mass photometry and size-exclusion chromatography demonstrated that RpR, even in an unformulated buffer, exhibits superior storage stability exceeding 10 months compared to aflibercept. Furthermore, microscale thermophoresis was employed to determine RpR's binding affinity to VEGF in solution, providing a more physiologically relevant assessment than traditional binding assays. These findings highlight RpR's potential as a therapeutic candidate for the treatment of AMD disease, warranting further investigation.},
}
@article {pmid39627894,
year = {2024},
author = {Lee, YM and Gurung, R and Gilhotra, JS and Simon, S and Cugati, S},
title = {Bilateral occlusive retinal vasculitis secondary to intravitreal faricimab injection: a case report and review of literature.},
journal = {Eye and vision (London, England)},
volume = {11},
number = {1},
pages = {48},
pmid = {39627894},
issn = {2326-0254},
abstract = {BACKGROUND: This article describes a rare occurrence of bilateral retinal occlusive vasculitis secondary to intravitreal faricimab injection.<br><br>CASE PRESENTATION: A 72-year-old female with age-related macular degeneration presented with bilateral retinal occlusive vasculitis following intravitreal faricimab injections. The patient was treated with 3&#xa0;days of intravenous methylprednisolone followed by oral prednisolone taper and topical steroid therapy. Resolution of retinal occlusive vasculitis was observed 2&#xa0;months post treatment.<br><br>CONCLUSIONS: Retinal occlusive vasculitis is a rare complication of intravitreal anti-vascular endothelial growth factor (anti-VEGF), particularly with faricimab injections. We also present a review of literature regarding retinal occlusive vasculitis following intravitreal anti-VEGF injections and propose further information regarding its pathophysiology.},
}
@article {pmid39625442,
year = {2024},
author = {Hiya, FE and Cheng, Y and Shen, M and Li, J and Berni, A and Zhou, SW and Herrera, G and O'Brien, RC and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {A Novel Grid Strategy for Correlating Focal Macular Anatomic Changes With Focal Changes in Choriocapillaris Perfusion.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {5},
pmid = {39625442},
issn = {1552-5783},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; Male ; Female ; Aged ; *Fluorescein Angiography/methods ; *Regional Blood Flow/physiology ; *Macula Lutea/diagnostic imaging/pathology/blood supply ; Middle Aged ; Aged, 80 and over ; Reproducibility of Results ; Fundus Oculi ; },
abstract = {PURPOSE: To establish the repeatability of choriocapillaris flow deficit (CCFD) measurements within a macular grid and then demonstrate the use of this registered grid strategy to follow CCFD measurements over time.<br><br>METHODS: Swept-source optical coherence tomography angiography scans were acquired (nominal size of 6 &#xd7; 6&#xa0;mm). For each scan, masks of hyperreflective foci, calcified drusen, and persistent choroidal hypertransmission defects (hyperTDs) were generated. These masks were then used to exclude these prespecified regions when calculating the CCFD percentages (CCFD%). Scans were registered, and CCFD% measurements were performed within 3-mm and 5-mm fovea-centered circles and within a fovea-centered grid (one box: 74 &#xd7; 74 pixels). The 95% minimal detectable changes (MDC95) for CCFD% were calculated for each of the regions. This longitudinal grid workflow was then used to study eyes before and after drusen resolved.<br><br>RESULTS: Ninety eyes of 63 patients were identified: 30 normal eyes, 30 eyes with intermediate age-related macular degeneration (iAMD), and 30 eyes with hyperTDs. The MDC95 for the normal, iAMD, and hyperTD eyes within the 3-mm and 5-mm circles ranged from 0.85% to 1.96%. The MDC95 for an individual grid's box ranged from 3.35% to 4.67%, and for the total grid area, the MDC95 ranged from 0.91% to 1.40%. When tested longitudinally before and after the resolution of drusen using grid strategy, no significant differences in the CCFD% were observed.<br><br>CONCLUSIONS: A grid strategy was developed to investigate targeted longitudinal changes in CCFD% associated with changes in optical coherence tomography biomarkers, and this strategy was validated using eyes in which drusen resolved.},
}
@article {pmid39625016,
year = {2024},
author = {Delcourt, C},
title = {[Effects of air pollution on eye health].},
journal = {La Revue du praticien},
volume = {74},
number = {9},
pages = {947-949},
pmid = {39625016},
issn = {2101-017X},
mesh = {Humans ; *Air Pollution/adverse effects ; *Eye Diseases/etiology/epidemiology/chemically induced ; Air Pollutants/adverse effects/analysis ; Particulate Matter/adverse effects/analysis ; },
abstract = {EFFECTS OF AIR POLLUTION ON EYE HEALTH. In addition to its well-known effects on cardio-respiratory health, air pollution could also have an impact on eye health. Indeed, certain air pollutants, especially fine particles and nitrogen dioxide, can enter the bloodstream, triggering oxidative and inflammatory mechanisms involved in the development of the major eye diseases (glaucoma, age-related macular degeneration [AMD], cataracts). Over the past 5 years, some 15 epidemiological studies carried out in Asia, Europe and Canada have consistently shown an increased risk of these diseases in individuals most exposed to air pollution at long term, particularly to fine particles. These results support the lowering of air pollution thresholds recommended by the World Health Organization (WHO) in 2021, which nevertheless continue to be exceeded in most European cities.},
}
@article {pmid39624796,
year = {2025},
author = {Nusinovici, S and Zhou, L and Raghavan, L and Tham, YC and Li, H and Cheung, D and Wang, X and Cheung, CMG and Wong, TY and Chakravarthy, U and Cheng, CY},
title = {Interplay between Lipids and Complement Proteins-How Multiomics Data Integration Can Help Unravel Age-related Macular Degeneration Pathophysiology: A Proof-of-concept Study.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100629},
pmid = {39624796},
issn = {2666-9145},
abstract = {OBJECTIVE: Our objectives were to identify correlation patterns between complement and lipid pathways using a multiomics data integration approach and to determine how these interconnections affect age-related macular degeneration (AMD).<br><br>DESIGN: Nested case-control study.<br><br>SUBJECTS AND CONTROLS: The analyses were performed in a subset of the Singapore Indian Eye Study. We randomly selected 155 AMD cases and age- and sex-matched them with 155 controls.<br><br>METHODS: Firstly, a multiomics data integration method was used to identify correlation patterns between the omics data. Then, we tested possible interactions between the lipids and complement proteins using logistic regression models.<br><br>MAIN OUTCOME MEASURES: Age-related macular degeneration was determined according to the Beckman classification system. We measured in serum samples 35 complement proteins and 66 lipids, and used 9 genetic variants.<br><br>RESULTS: Among the 155 AMD cases, 93 (60.0%) had early and 62 (40.0%) intermediate AMD. Firstly, we identified 2 clusters between complement proteins and lipids involving (1) mannan-binding lectin serine protease 1 and several different high-density lipoprotein particles, and (2) complement factor H-related protein 1, carboxypeptidase N subunit 2 and complement component C8 gamma chain, and sphingomyelin and different cholesterol. Secondly, we identified 1 interaction between complement protein 1R and sphingomyelin with an odds of AMD 2 times higher for individuals with low levels of sphingomyelin and complement protein 1R (odds ratio&#xa0;=&#xa0;2.13 [1.09, 4.17]).<br><br>CONCLUSIONS: We report here, using a cutting-edge multiomics integration approach, the complex interconnections between genetic, metabolomics, and proteomic data. This method permitted us to obtain a holistic picture and identify multiomics signature of AMD pathophysiology. These results advocate for a personalized therapeutic approach that accounts for multiple pathways. However, these results need to be validated in larger studies with different ethnic groups.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39623103,
year = {2024},
author = {Gorman, BR and Voloudakis, G and Igo, RP and Kinzy, T and Halladay, CW and Bigdeli, TB and Zeng, B and Venkatesh, S and Cooke Bailey, JN and Crawford, DC and Markianos, K and Dong, F and Schreiner, PA and Zhang, W and , and , and Hadi, T and Anger, MD and Stockwell, A and Melles, RB and Yin, J and Choquet, H and Kaye, R and Patasova, K and Patel, PJ and Yaspan, BL and Jorgenson, E and Hysi, PG and Lotery, AJ and Gaziano, JM and Tsao, PS and Fliesler, SJ and Sullivan, JM and Greenberg, PB and Wu, WC and Assimes, TL and Pyarajan, S and Roussos, P and Peachey, NS and Iyengar, SK},
title = {Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries.},
journal = {Nature genetics},
volume = {56},
number = {12},
pages = {2659-2671},
pmid = {39623103},
issn = {1546-1718},
support = {IK6BX005233//Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development)/ ; I01BX004557//Research to Prevent Blindness (RPB)/ ; I01BX003364//Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development)/ ; R01 EY029315/EY/NEI NIH HHS/United States ; R01 EY033298/EY/NEI NIH HHS/United States ; R01 EY007361/EY/NEI NIH HHS/United States ; IK6 BX005787/BX/BLRD VA/United States ; R01 EY028203/EY/NEI NIH HHS/United States ; R01 EY013435/EY/NEI NIH HHS/United States ; I01BX004189//Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development)/ ; },
mesh = {Aged ; Female ; Humans ; Male ; Black People/genetics ; Complement Factor H/genetics ; *Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Haplotypes ; High-Temperature Requirement A Serine Peptidase 1/genetics ; Hispanic or Latino/genetics ; *Macular Degeneration/genetics ; *Polymorphism, Single Nucleotide ; Proteins/genetics ; },
abstract = {To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, knowledge of its genetic architecture in diverse populations is necessary. A critical element, AMD risk profiles in African and Hispanic/Latino ancestries, remains largely unknown. We combined data in the Million Veteran Program with five other cohorts to conduct the first multi-ancestry genome-wide association study of AMD and discovered 63 loci (30 novel). We observe marked cross-ancestry heterogeneity at major risk loci, especially in African-ancestry populations which demonstrate a primary signal in a major histocompatibility complex class II haplotype and reduced risk at the established CFH and ARMS2/HTRA1 loci. Dissecting local ancestry in admixed individuals, we find significantly smaller marginal effect sizes for CFH risk alleles in African ancestry haplotypes. Broadening efforts to include ancestrally distinct populations helped uncover genes and pathways that boost risk in an ancestry-dependent manner and are potential targets for corrective therapies.},
}
@article {pmid39622926,
year = {2024},
author = {Lee, DMW and Zhang, M and Snyder, VC and Rossi, EA},
title = {Multi-spectral autofluorescence variability of the individual retinal pigmented epithelial cells in healthy aging eyes.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30012},
pmid = {39622926},
issn = {2045-2322},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; R01 EY030517/EY/NEI NIH HHS/United States ; EY030517/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/cytology/metabolism ; Middle Aged ; Adult ; Aged ; Female ; Male ; *Ophthalmoscopy/methods ; Optical Imaging/methods ; Aging/physiology ; Young Adult ; Healthy Aging ; Epithelial Cells/metabolism/cytology ; },
abstract = {The retinal pigment epithelium (RPE) is vital for the healthy function of the retina. Cellular level changes in the RPE are not visualized with current clinical techniques due to a lack of spatial resolution. Fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) can image RPE cells by utilizing their intrinsic autofluorescence (AF). The RPE AF has been imaged with only a few discrete excitation and emission bands and the multi-spectral AF has not been interrogated systematically at the level of single cells. In this study, we imaged 16 healthy eyes (ages 20-75) with AOSLO to investigate the multi-spectral AF as a function of age and wavelength with excitation from 650 - 805 nm. Quantitative analysis showed that 720 nm light produced images with the highest SNR (65.0 dB). Spatial AF variability showed a trend to increase with aging, suggesting increased heterogeneity in RPE AF with age. Spatial variability in the multi-spectral fluorescence of RPE cells with age may be a consequence of normal age-related loss of RPE cells. Multi-spectral fluorescence AOSLO provides new insight into aging related changes to RPE cells and may be a useful tool for studying diseases that affect the RPE, such as age-related macular degeneration (AMD).},
}
@article {pmid39622437,
year = {2024},
author = {Jonas, JB and Panda-Jonas, S and Dong, L and Jonas, RA},
title = {Clinical and anatomical features of myopia.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {6},
pages = {100114},
doi = {10.1016/j.apjo.2024.100114},
pmid = {39622437},
issn = {2162-0989},
mesh = {Humans ; *Myopia/pathology/physiopathology ; Visual Acuity ; Bruch Membrane/pathology ; Tomography, Optical Coherence/methods ; },
abstract = {The purpose of the review is to summarize clinical and anatomically-related aspects of myopia. Recent studies have revealed macular atrophy as myopic maculopathy (MMP) stage-4 was accompanied by a central Bruch´s membrane (BM) defect associated with a subretinal proliferation (as sign of previous macular neovascularization). Patchy atrophies (MMP-stage 3) could be differentiated into those without versus with BM defects/subretinal proliferations. BM defects and subretinal proliferations were associated with each other (OR: 78.3; P < 0.001). Fundus tessellation as MMP-stage-1 correlated with visual acuity reduction, suggesting pathological changes already at MMP stage 1, in addition to a leptochoroid as risk factor. Myopic parapapillary beta zone (potentially caused by an axial elongation-related enlargement of the retinal pigment epithelium [RPE] layer opening; characterized by small or no alpha zone, few or no RPE drusen at its border, normal BM thickness) can be differentiated from glaucomatous parapapillary beta zone (characterized by alpha zone, RPE drusen, and thickened BM). The overlying retinal layers extended into the parapapillary zones, deeper than the superficial layers. Prevalence of non-glaucomatous optic neuropathy increased non-linearly with longer axial length in highly myopic eyes and was a major cause for vision loss in high myopia. In patients aged 85 + years, prevalence of MMP stage 3 or 4 in highly myopic eyes (axial length ≥ 26.5 mm) was about 75 %. Myopia was associated with a lower prevalence of diabetic retinopathy, age-related macular degeneration and angle-closure glaucoma, while high myopia, more than moderate myopia, was associated with higher prevalence and incidence of open-angle glaucoma.},
}
@article {pmid39620832,
year = {2024},
author = {Calton, MA and Croze, RH and Burns, C and Beliakoff, G and Vazin, T and Szymanski, P and Schmitt, C and Klein, A and Leong, M and Quezada, M and Holt, J and Bolender, G and Barglow, K and Khoday, D and Mason, T and Delaria, K and Hassanipour, M and Kotterman, M and Khanani, AM and Schaffer, D and Francis, P and Kirn, D},
title = {Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {14},
pages = {1},
pmid = {39620832},
issn = {1552-5783},
mesh = {Animals ; *Intravitreal Injections ; Humans ; *Genetic Therapy/methods ; *Dependovirus/genetics ; *Transgenes ; *Genetic Vectors ; Disease Models, Animal ; Vascular Endothelial Growth Factor A/genetics ; Macaca mulatta ; Receptors, Vascular Endothelial Growth Factor/genetics/administration &amp; dosage ; Choroidal Neovascularization/genetics/therapy ; Retinal Pigment Epithelium/metabolism ; Wet Macular Degeneration/genetics/therapy ; Macaca fascicularis ; Recombinant Fusion Proteins ; },
abstract = {PURPOSE: Intravitreal delivery of therapeutic transgenes to the retina via engineered viral vectors can provide sustained local concentrations of therapeutic proteins and thus potentially reduce the treatment burden and improve long-term vision outcomes for patients with neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy.<br><br>METHODS: We performed directed evolution in nonhuman primates (NHP) to invent an adeno-associated viral (AAV) variant (R100) with the capacity to cross vitreoretinal barriers and transduce all regions and layers of the retina following intravitreal injection. We then engineered 4D-150, an R100-based genetic medicine carrying 2 therapeutic transgenes: a codon-optimized sequence encoding aflibercept, a recombinant protein that inhibits VEGF-A, VEGF-B, and PlGF, and a microRNA sequence that inhibits expression of VEGF-C. Transduction, transgene expression, and biological activity were characterized in human retinal cells in vitro and in NHPs.<br><br>RESULTS: R100 demonstrated superior retinal cell transduction in vitro and in vivo compared to AAV2, a commonly used wild-type AAV serotype in retinal gene therapies. Transduction of human retinal pigment epithelial cells in vitro by 4D-150 resulted in dose-dependent transgene expression and corresponding reductions in VEGF-A and VEGF-C. Intravitreal administration of 4D-150 to NHPs was well tolerated and led to robust retinal expression of both transgenes. In a primate model of laser-induced choroidal neovascularization, 4D-150 completely prevented clinically relevant angiogenic lesions at all tested doses.<br><br>CONCLUSIONS: These findings support further development of 4D-150. Clinical trials are underway to establish the safety and efficacy of 4D-150 in individuals with wet AMD and DME.},
}
@article {pmid39620667,
year = {2024},
author = {Singh, DV and Agarwal, A and Goyal, A and Shroff, D and Singh, J and Kumar, P and Reddy, RR and Venkatesh, R and Narnaware, S and Joshi, S and Singh, DV and Narula, R and Joshi, A and Agarwal, A and Goyal, A and Gupta, C and Shroff, D and Anantharaman, G and Singh, J and Kumar, P and Bawankule, P and Reddy, RR and Jain, R and Venkatesh, R and Tiwari, R and Sugumar, S and Gupta, SR and Narnaware, S and Joshi, S and Choudhary, SP and , },
title = {Initial experience with brolucizumab for neovascular age-related macular degeneration (nAMD) in India - Multicentric, real-world study.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {12},
pages = {1786-1794},
pmid = {39620667},
issn = {1998-3689},
mesh = {Humans ; *Intravitreal Injections ; Male ; India/epidemiology ; Retrospective Studies ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Tomography, Optical Coherence/methods ; Follow-Up Studies ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Fundus Oculi ; Aged, 80 and over ; },
abstract = {PURPOSE: To evaluate the anatomic and visual outcomes and safety profile of initial Indian eyes with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab.<br><br>METHODS: This retrospective multicentric, real-world study enrolled consecutive eyes with nAMD that were treated with IVI brolucizumab after it was launched in India in October 2020. Data collected for each eye included best-corrected visual acuity (BCVA), central subfield thickness (CSFT), subretinal fluid (SRF), and intraretinal fluid (IRF) status at 6, 12, and 24 months follow-up. Also recorded were the lens status, treatment protocol, number of injections received before enrollment (in switch-over cases), total number of injections, and adverse effects noticed during the study period. Primary outcomes were change in BCVA, CSFT at follow-up visits, and incidence of intraocular inflammation (IOI). Secondary outcomes were profile of macular neovascularization, treatment protocols, mean number of injections, and maximum injection-free interval observed in eyes treated by pro-re-nata (PRN) protocol.<br><br>RESULTS: In total, 331 eyes received a mean of 3.55 &#xb1; 1.83 injections. Most frequent treatment protocol was PRN (53%). BCVA data was available for 100%, 96%, and 74% eyes at 6, 12, and 24 months follow-up. BCVA and CSFT improved significantly (P < 0.001) at all follow-ups. Two hundred and seventy-six (83.38%) out of 331 eyes received more than one injection; out of these, 241 (87.3%) eyes that were treated by PRN protocol could achieve mean "maximum injection-free interval" of 19.43 &#xb1; 8.82 weeks. IOI and retinal vasculitis were reported in 2.11% (7/331) and 0.60% (2/331) eyes, respectively. None of the eyes with IOI or vasculitis lost any vision at the final follow-up.<br><br>CONCLUSION: This study demonstrated favorable visual and anatomic outcomes and safety profile for eyes with nAMD treated by IVI brolucizumab. Mean maximum injection-free interval in eyes treated with PRN was 19 weeks.},
}
@article {pmid39617060,
year = {2025},
author = {Cheung, CMG and Lim, JI and Priglinger, S and Querques, G and Margaron, P and Patel, S and Souverain, A and Willis, JR and Yang, M and Guymer, R},
title = {Anatomic Outcomes with Faricimab vs Aflibercept in Head-to-Head Dosing Phase of the TENAYA/LUCERNE Trials in Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology},
volume = {132},
number = {5},
pages = {519-526},
doi = {10.1016/j.ophtha.2024.11.023},
pmid = {39617060},
issn = {1549-4713},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage ; Intravitreal Injections ; Male ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged ; *Visual Acuity/physiology ; Double-Blind Method ; Tomography, Optical Coherence/methods ; Middle Aged ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Dose-Response Relationship, Drug ; Aged, 80 and over ; *Macula Lutea/pathology ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To compare early anatomic outcomes after treatment with faricimab versus aflibercept in a pooled analysis of the head-to-head dosing phase of the TENAYA/LUCERNE trials in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: TENAYA/LUCERNE (NCT03823287/NCT03823300) were identical, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.<br><br>PARTICIPANTS: Patients aged &#x2265; 50 years with treatment-na&#xef;ve nAMD.<br><br>METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) after 4 initial doses every 4 weeks (Q4W) or aflibercept 2.0 mg every 8 weeks (Q8W) after 3 initial doses given Q4W.<br><br>MAIN OUTCOME MEASURES: Post hoc analyses comparing faricimab with aflibercept in terms of change in central subfield thickness (CST) from baseline and proportion of patients with an absence of subretinal fluid (SRF) and intraretinal fluid (IRF) during initial 12-week head-to-head dosing phase, when both arms received 3 injections, and time to first absence of IRF and SRF.<br><br>RESULTS: A total of 1329 patients were enrolled across TENAYA/LUCERNE (n&#xa0;= 665 faricimab; n&#xa0;= 664 aflibercept). There were greater (nominal P < 0.0001) reductions in adjusted mean CST from baseline with faricimab versus aflibercept at weeks 4, 8, and 12, with comparable vision outcomes. At week 12, more patients (95% confidence interval) achieved an absence of SRF (87.9% [85.4%-90.4%] vs. 79.0% [76.0%-82.1%]) and both IRF and SRF (77.2% [74.0%-80.4%] vs. 66.5% [62.9%-70.0%]) but not IRF (88.4% [86.0%-90.8%] vs. 85.0% [82.3%-87.6%]), with faricimab versus aflibercept, respectively. In patients with IRF or SRF at baseline (n&#xa0;= 581 faricimab; n&#xa0;= 591 aflibercept), the 75th percentile of time to first absence of IRF and SRF was reached at week 8 with faricimab and week 12 with aflibercept. At week 12, cumulative incidence of first-time absence of IRF and SRF was 85.5% (82.3%-88.1%) with faricimab and 75.0% (71.3%-78.3%) with aflibercept.<br><br>CONCLUSIONS: Faricimab resulted in greater improvement in anatomic outcomes than aflibercept during the head-to-head dosing phase and a faster time to first absence of retinal fluid.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39617059,
year = {2025},
author = {Froines, CP and Pak, JW and Agrón, E and Chew, EY and Peto, T and Blodi, BA and Domalpally, A},
title = {Longitudinal Assessment of Age-Related Macular Degeneration Using Ultrawidefield Imaging: The Optos Peripheral Retina Follow-up Study.},
journal = {Ophthalmology},
volume = {132},
number = {5},
pages = {569-577},
pmid = {39617059},
issn = {1549-4713},
support = {ZIA EY000485/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Aged ; Follow-Up Studies ; Disease Progression ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Wet Macular Degeneration/diagnosis ; Tomography, Optical Coherence/methods ; Middle Aged ; Longitudinal Studies ; *Retina/pathology ; Retinal Drusen/diagnosis ; Geographic Atrophy/diagnosis ; Visual Acuity ; },
abstract = {PURPOSE: With the widespread availability of Ultrawidefield (UWF) imaging, peripheral retinal abnormalities in age-related macular degeneration (AMD) have garnered attention. However, longitudinal studies of AMD peripheral findings are limited. This study aimed to characterize and quantify these features over 5 years.<br><br>DESIGN: Longitudinal ancillary study.<br><br>PARTICIPANTS: The Optos Peripheral Retina (OPERA) study was an ancillary study of the Age-Related Eye Disease Study 2. A total of 137 participants (265 eyes) in the OPERA study with gradable UWF color and autofluorescence imaging at years 5 and 10 were included.<br><br>METHODS: Ultrawidefield color and autofluorescence images were captured using Optos UWF devices and were graded at the Wisconsin Reading Center for macular and peripheral AMD features using the 3-zone OPERA study grid.<br><br>MAIN OUTCOME MEASURES: Presence of peripheral retinal lesions (neovascular AMD, geographic atrophy [GA], drusen, increased pigment, decreased pigment, reticular pseudodrusen, reticular pigmentary changes, and cobblestone degeneration) and their association with central AMD progression.<br><br>RESULTS: In zone 1 at year 5 and year 10, the AMD severity scale (AMDSS) score was &#x2264; 5 in 8% and 6%, 6 to 8 in 49% and 30%, noncentral and central GA in 15% and 27%, and neovascular AMD in 28% and 37%, respectively. In zone 2, peripheral AMD abnormalities in year 5 versus year 10 included: drusen, 99% versus 99%; hyperpigmentation, 11% versus 11%; and hypopigmentation, 4% versus 7%, respectively. Peripheral degenerations not associated with AMD were present in year 5 versus year 10 as follows: cobblestone, 19% versus 30%; and reticular pigmentary changes, 25% versus 33%, respectively. Among eyes with an AMDSS level of 6 to 8 at year 5, progression to late AMD occurred in 41% without substantial peripheral findings and in 41% with such findings, which include drusen of &#x2265; 1 disc area, any hypopigmentation or hyperpigmentation in zones 2 or 3, or a combination thereof.<br><br>CONCLUSIONS: The OPERA study revealed that AMD features often extend beyond the macula, suggesting that AMD is a panretinal disease. In this study, peripheral findings were not associated with increased risk of progression to late AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39615827,
year = {2025},
author = {Wang, D and Tang, T and Wang, Y and Zhao, J and Shen, B and Zhang, M},
title = {Integrative analysis and knowledgebase construction of key candidate genes and pathways in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {251},
number = {},
pages = {110177},
doi = {10.1016/j.exer.2024.110177},
pmid = {39615827},
issn = {1096-0007},
mesh = {Humans ; *Macular Degeneration/genetics/metabolism ; *Knowledge Bases ; Vascular Endothelial Growth Factor A/genetics ; Polymorphism, Single Nucleotide ; Databases, Genetic ; Genetic Variation ; Genetic Predisposition to Disease ; },
abstract = {Age-related macular degeneration is a retinal disease that severely impacts vision in the older population. Its gene-related heterogeneity has not been fully studied, increasing the burden of precise treatment, prevention and prognosis. Genetic variation and related information were collected, annotated and expanded from multiple related websites, and all the data were integrated into the online platform AMDGKB. Users can visit this database via the following link: http://amdgd.bioinf.org.cn/for their personalized applications knowledge-guided modeling and applications. This study also explored the heterogeneity of ethnicity and AMD subtypes via genetic variation, functional enrichment analysis and protein‒protein interactions. These results suggest that VEGFA, MT2A, CCL2 and SERPINF1 play different roles in the development of AMD in different ethnic groups. The enrichment analysis also revealed differences in the pathogenesis pathways of different ethnic groups and AMD subtypes. This study highlights that genetic heterogeneity needs to be considered in the process of diagnosis and treatment. AMDGKB provides information for investigating the transformation of genetic variation during AMD progression, as well as for future personalized applications in the diagnosis and prognosis of AMD.},
}
@article {pmid39615671,
year = {2025},
author = {Hössl, L and Vaghefi, SA and Riemer, T and Kabiri, P and Bonaventura, T and Rübsam, A and Joussen, AM and Zeitz, O},
title = {Insights into Cataract Surgery Outcomes in Age-Related Macular Degeneration: Perspectives across Severity Grades Under Clinical Routine Conditions.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {6},
pages = {527-536},
doi = {10.1016/j.oret.2024.11.018},
pmid = {39615671},
issn = {2468-6530},
mesh = {Humans ; Retrospective Studies ; *Visual Acuity ; Male ; Female ; Tomography, Optical Coherence/methods ; Aged ; Follow-Up Studies ; *Cataract/complications/diagnosis ; *Cataract Extraction/methods ; *Wet Macular Degeneration/complications/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Severity of Illness Index ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Intravitreal Injections ; },
abstract = {PURPOSE: Cataract and age-related macular degeneration (AMD) share age as a main risk factor and thus have a high coincidence. Both conditions substantially reduce visual acuity. This study aimed to assess the impact of cataract surgery on visual acuity, retinal morphology, and VEGF inhibitor therapy in patients with AMD.<br><br>DESIGN: This study was designed as a retrospective, monocentric, real-world study.<br><br>SUBJECTS: Patients diagnosed with either dry AMD or neovascular AMD undergoing cataract surgery at Charit&#xe9; Campus Benjamin Franklin.<br><br>METHODS: Treatment data were extracted from the Berlin Macular Registry. Best-corrected visual acuity (BCVA) and macular OCT parameters, including central retinal thickness (CRT), macular volume (MV), presence of macular edema, intraretinal or subretinal fluid, and pigment epithelial detachment were assessed.<br><br>MAIN OUTCOME MEASURES: The primary outcome measure was the postoperative BCVA. Secondary outcomes included postoperative CRT, MV, changes in qualitative OCT parameters, alterations in anti-VEGF-therapy interval, and postoperative complications.<br><br>RESULTS: A total of 418 eyes of 418 patients were included in the analysis with a mean follow-up time of 18.8 (2-62) months. They were classified into a neovascular AMD (n = 85) and a dry AMD (n = 333) cohort. Mean BCVA improved significantly in the neovascular AMD cohort from 0.69 &#xb1; 0.45 logarithm of the minimum angle of resolution (logMAR) to 0.47 &#xb1; 0.42 (P < 0.001) and in the dry AMD cohort from 0.53 &#xb1; 0.47 logMAR to 0.27 &#xb1; 0.32 (P < 0.001) at the 2-month follow-up. Improvements in BCVA were sustained to the final visit (18.8 &#xb1; 19.5 months after surgery) with BCVA at 0.46 &#xb1; 0.38 logMAR (P < 0.001) and 0.26 &#xb1; 0.34 logMAR (P < 0.001), respectively. Temporary postoperative increases in CRT and MV were observed, reverting to preoperative levels by 6 months after surgery. The need for anti-VEGF therapy did not change postoperatively in patients with neovascular AMD.<br><br>CONCLUSIONS: Within this retrospective analysis, on average, patients with coincident AMD of all severity grades meeting the inclusion criteria benefited from cataract surgery. Transient increases in retinal thickness and MV returned to baseline within 6 months after surgery. The need for intravitreal injections in neovascular AMD subjects was unchanged after surgery. Overall, the study suggests no adverse long-term macular changes attributable to cataract surgery.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39615233,
year = {2025},
author = {M, R and R, L and Benitez, R},
title = {Interpretable diagnostic system for multiocular diseases based on hybrid meta-heuristic feature selection.},
journal = {Computers in biology and medicine},
volume = {184},
number = {},
pages = {109486},
doi = {10.1016/j.compbiomed.2024.109486},
pmid = {39615233},
issn = {1879-0534},
mesh = {Humans ; *Algorithms ; Eye Diseases/diagnosis/diagnostic imaging ; Diagnosis, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging/diagnosis ; Heuristics ; },
abstract = {Age-related Macular Degeneration (AMD), Cataract, Diabetic Retinopathy (DR) and Glaucoma are the four most common ocular conditions that affect a person's vision. Early detection in the asymptomatic stages can alleviate vision loss or slow down the progression of these diseases. However, manual diagnosis is a costly and tedious process, especially in mass screening applications. Computer aided diagnosis (CAD) systems serve as an aid to ophthalmologists in efficient diagnosis of ocular diseases. In particular, a generic CAD framework that detects multiple ocular diseases could be immensely beneficial. In the proposed work, a single framework for detection of the above-mentioned ocular diseases has been explored. Specifically, a pool of non-linear handcrafted features are extracted from fundus images, followed by feature selection using a hybrid optimization algorithm, where features are selected using JAYA algorithm (JA) first, followed sequentially by the Harris hawks optimization (HHO) algorithm. The selected features are used to train an extreme gradient boosting (XGB) model for disease classification. Unlike existing systems that restrict non-linear features to single ocular disease detection, the proposed system is the first of its kind for detection of the above-specified multiple ocular diseases in a generic framework, yielding 93 % accuracy, 91.3 % sensitivity, 96.4 % specificity, 90.4 % precision and 90.8 % F1 score. Further, in this study, Shapley additive explanations (SHAP) analysis is employed to gain insight on the impact of the non-linear features on the model's prediction capability. This work clearly demonstrates the importance of explainability that opens the 'black box' nature of machine learning (ML) model and clearly unveils the relationships among the features and the diagnosis. Also, the explainable ML model improves transparency of the model's decision-making process. The proposed algorithm can efficiently assist physicians in diagnosing the ocular diseases using fundus images in clinical practice, and avoids the subjective difference that comes with manual assessment.},
}
@article {pmid39614439,
year = {2024},
author = {Geathers, JS and Grillo, SL and Karakoleva, E and Campbell, GP and Du, Y and Chen, H and Barber, AJ and Zhao, Y and Sundstrom, JM},
title = {Sodium Iodate: Rapid and Clinically Relevant Model of AMD.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {29},
number = {11},
pages = {380},
doi = {10.31083/j.fbl2911380},
pmid = {39614439},
issn = {2768-6698},
support = {//Bennett and Inez Chotiner Early Career Professorship in Ophthalmology endowment (JMS)/ ; },
mesh = {Animals ; *Iodates/toxicity ; *Disease Models, Animal ; Male ; *Mice, Inbred C57BL ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging/pathology/etiology ; Mice ; Retina/diagnostic imaging/pathology/drug effects ; Retinal Pigment Epithelium/pathology/drug effects/diagnostic imaging/metabolism ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of vision loss in people above the age of 50, affecting approximately 10% of the population worldwide and the incidence is rising. Hyperreflective foci (HRF) are a major predictor of AMD progression. The purpose of this study was to use the sodium iodate mouse model to study HRF formation in retinal degeneration.<br><br>METHODS: Sodium iodate (NaIO3) treated rodents were studied to characterize HRF. 3-month-old male wild-type (WT) C57Bl/6J mice were injected with phosphate-buffered saline (PBS) or varying doses of NaIO3 (15-60 mg/kg). Optical Coherence Tomography (OCT) images were collected at baseline and several days post-NaIO3 injection. Retinal thicknesses were measured using Bioptigen software. Seven days post-injection, eyes were prepared for either transmission electron microscopy (TEM), Hematoxylin &amp; Eosin (H&amp;E), or immunofluorescence.<br><br>RESULTS: OCT imaging of the mice given higher doses of NaIO3 revealed HRF formation in the neural retina (n = 4). The amount of HRF correlated with the degree of retinal tissue loss. H&amp;E and TEM imaging of the retinas seven days post-NaIO3 injection revealed several pigmented bodies in multiple layers of the retina (n = 3-5). Immunofluorescence revealed that some pigmented bodies were positive for macrophage markers and an epithelial-to-mesenchymal transition marker, while all were retinal pigment epithelium (RPE) 65-negative (n = 4).<br><br>CONCLUSIONS: The data suggest that NaIO3 induces the formation of HRF in the outer retina and their abundance correlates with retinal tissue loss. The experiments in this study highlight NaIO3 as a clinically relevant model of intermediate AMD that can be used to study HRF formation and to discover new treatment targets.},
}
@article {pmid39613904,
year = {2025},
author = {Foster, MJ and Chu, J and Shaia, J and Singh, RP and Talcott, KE},
title = {Prevalence and diversity of retinal disease in adults with Down syndrome.},
journal = {Eye (London, England)},
volume = {39},
number = {3},
pages = {505-515},
pmid = {39613904},
issn = {1476-5454},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; P30EY025585(BA-A)//Research to Prevent Blindness (RPB)/ ; },
mesh = {Humans ; *Down Syndrome/epidemiology/complications ; Prevalence ; *Retinal Diseases/epidemiology ; Adult ; United States/epidemiology ; },
abstract = {While epidemiologic data exists for some ophthalmic diseases in people with Down Syndrome (DS), like strabismus and amblyopia, no studies explore the prevalence of retinal disease in people with DS on a large scale. This study utilized a literature review and exploratory epidemiology analysis to examine patterns of retinal disease in people with DS. To evaluate previous studies on physiology and/or anatomy in retinal models representing DS or in the retinas of people with DS, all relevant terms related to Down Syndrome, retina, and retinal diseases were searched in PubMed and Scopus. Data from the health platform TriNetX was then utilized to determine the prevalence and prevalence odds ratio (POR) of retinal disorders, including diabetic retinopathy and age-related macular degeneration (AMD), within the U.S. adult population with DS. The final literature review included 28 of 535 screened studies and found that a DS diagnosis was associated with atypical retinal vascularization, retinal thickening, and abnormal neuronal development. Of 55,198,979 individuals included in the population study, 97,795 (0.18%) had a recorded DS diagnosis. Compared to the population without DS, the population with DS had significantly increased PORs for any retinal diagnosis (3.78, 95% CI 3.63-3.93), for 16 of 18 recorded individual retinal diagnoses, and for 4 of 5 major diagnostic categories, including diabetic retinopathy (2.56, 95% CI 2.33-2.82) and macular degeneration (4.01, 95% CI 3.42-4.71). The conclusion is that retinal anomalies common to people with DS likely contribute to higher rates of recorded retinal disease. However, future studies should evaluate this relationship.},
}
@article {pmid39611043,
year = {2024},
author = {Wang, Y and Gao, S and Cao, F and Yang, H and Lei, F and Hou, S},
title = {Ocular immune-related diseases: molecular mechanisms and therapy.},
journal = {MedComm},
volume = {5},
number = {12},
pages = {e70021},
pmid = {39611043},
issn = {2688-2663},
abstract = {Ocular immune-related diseases, represent a spectrum of conditions driven by immune system dysregulation, include but not limit to uveitis, diabetic retinopathy, age-related macular degeneration, Graves' ophthalmopathy, etc. The molecular and cellular mechanisms underlying these diseases are typically dysfunctioned immune responses targeting ocular tissues, resulting in inflammation and tissue damage. Recent advances have further elucidated the pivotal role of different immune responses in the development, progression, as well as management of various ocular immune diseases. However, there is currently a relative lack of connection between the cellular mechanisms and treatments of several immune-related ocular diseases. In this review, we discuss recent findings related to the immunopathogenesis of above-mentioned diseases. In particular, we summarize the different types of immune cells, inflammatory mediators, and associated signaling pathways that are involved in the pathophysiology of above-mentioned ophthalmopathies. Furthermore, we also discuss the future directions of utilizing anti-inflammatory regime in the management of these diseases. This will facilitate a better understanding of the pathogenesis of immune-related ocular diseases and provide new insights for future treatment approaches.},
}
@article {pmid39610566,
year = {2024},
author = {Kha, R and Jin, I and Tang, D and Liew, G and Craig, A and Burlutsky, G and Mitchell, P and Gopinath, B},
title = {Effectiveness of a Novel Multimodal Intervention for Family Caregivers of Persons With Age-Related Macular Degeneration: A Randomized Controlled Trial.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e72523},
pmid = {39610566},
issn = {2168-8184},
abstract = {Purpose Age-related macular degeneration (AMD) is a leading cause of visual impairment in older adults. Individuals affected by AMD often require regular physical and emotional support from family caregivers. Carers of people with AMD endure significant physical burdens, emotional distress, increased financial stress, and disruptions due to their lifestyle and retirement plans as a direct consequence of the AMD caregiving experience. Despite this, there are currently no interventions targeted toward family caregivers of AMD patients. We evaluated the efficacy of a novel intervention aiming to improve the burden and well-being of family carers of persons with AMD. Methods Family carers of relatives with AMD were primarily recruited through private eye clinics and randomized 1:1 to either receive a 10-week intervention of mail-delivered cognitive behavioral therapy (M-CBT) and optional telephone-delivered group counseling (n = 47) or to a wait-list control group (n = 47). Outcome measures were assessed pre-intervention (baseline) and six months post-intervention. These included treatment acceptability, caregiver burden, presence of depressive symptoms, self-efficacy, quality of life (QoL), and fatigue. Results A total of 94 participants were enrolled, with 47 randomized to each arm. Of those who completed the intervention, 30 (97%) participants reported that they were satisfied/very satisfied with the intervention. Twenty-seven (87%) participants indicated that they would recommend the program to others, and 26 (84%) thought that the program was worth their time. Intervention participants demonstrated several positive nonsignificant improvements versus the control group at six months: burden (P= 0.53), depressive symptoms (P= 0.19), general self-efficacy (P= 0.14), QoL (P= 0.17) and fatigue (P= 0.15). Conclusions Study findings demonstrate that combined M-CBT and telephone counseling intervention appear to be feasible, but did not lead to nonsignificant improvements in outcome measures such as burden in family carers of persons with AMD.},
}
@article {pmid39610324,
year = {2025},
author = {Willoughby, JJ and Jensen, AM},
title = {Abca4, mutated in Stargardt disease, is required for structural integrity of cone outer segments.},
journal = {Disease models &amp; mechanisms},
volume = {18},
number = {1},
pages = {},
pmid = {39610324},
issn = {1754-8411},
support = {BR-CMM-0622-0835-UMASS/FFB/Foundation Fighting Blindness/United States ; NA//University of Massachusetts CNS Bridge and Seed Funding grant/ ; //College of Natural Sciences, University of Massachusetts Amherst/ ; 1951420//National Science Foundation/ ; //University of Massachusetts Amherst/ ; S10 OD025113/OD/NIH HHS/United States ; },
mesh = {*Zebrafish/genetics ; Animals ; *ATP-Binding Cassette Transporters/genetics/metabolism ; *Stargardt Disease/pathology/genetics ; *Mutation/genetics ; Humans ; *Phagocytosis ; *Zebrafish Proteins/genetics/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *Retinal Cone Photoreceptor Cells/pathology/metabolism ; Retinal Photoreceptor Cell Outer Segment/metabolism/pathology ; Macular Degeneration/genetics/pathology/congenital ; Phosphatidylserines/metabolism ; Apoptosis/genetics ; },
abstract = {Stargardt disease (STGD), the leading cause of inherited childhood blindness, is primarily caused by mutations in the ABCA4 gene; yet, the underlying mechanisms of photoreceptor degeneration remain elusive, partly due to limitations in existing animal disease models. To expand our understanding, we mutated the human ABCA4 paralogues abca4a and abca4b in zebrafish, which has a cone-rich retina. Our study unveiled striking dysmorphology and elongation of cone outer segments (COS) in abca4a;abca4b double mutants, alongside reduced phagocytosis by the retinal pigmented epithelium (RPE). We report that zebrafish Abca4 protein forms a distinctive stripe along the length of COS, suggesting a potential structural role. We further show that, in wild-type zebrafish, outer segments of cone cells constitutively present externalized phosphatidylserine, an apoptotic 'eat-me' signal, and that this pattern is disrupted in abca4a;abca4b double mutants, potentially contributing to reduced RPE phagocytic activity. More broadly, constitutive presentation of the 'eat-me' signal by COS - if conserved in humans - might have important implications for other retinal degenerative diseases, including age-related macular degeneration. Our zebrafish model provides novel insights into cone dysfunction and presents a promising platform for unraveling the mechanisms of STGD pathogenesis and advancing therapeutic interventions.},
}
@article {pmid39607311,
year = {2025},
author = {Khossravi, AS and Chen, Q and Adelman, RA},
title = {Artificial intelligence in ophthalmology.},
journal = {Current opinion in ophthalmology},
volume = {36},
number = {1},
pages = {35-38},
doi = {10.1097/ICU.0000000000001111},
pmid = {39607311},
issn = {1531-7021},
mesh = {Humans ; *Artificial Intelligence ; *Ophthalmology/methods/trends ; *Eye Diseases/diagnosis/therapy ; Diagnostic Techniques, Ophthalmological ; },
abstract = {PURPOSE OF REVIEW: To review role of artificial intelligence in medicine.<br><br>RECENT FINDINGS: Artificial intelligence is continuing to revolutionize access, diagnosis, personalization of medicine, and treatment in healthcare. As a matter of fact, artificial intelligence contributed to the research that resulted in 2024 Nobel Prizes in physics, chemistry, and economics. We are only at the tip of the iceberg in utilizing the abilities of artificial intelligence in medicine to improve accuracy of diagnoses and to enhance patient outcomes. Artificial intelligence has allowed better image analysis, prediction of progression of disease, personalized treatment plans, incorporations of genomics, and improved efficiency in care and follow-up utilizing home monitoring. In ocular health diagnosis and treatment of diabetic retinopathy, macular degeneration, glaucoma, corneal infections, and ectasia are only a few examples of how the power of artificial intelligence has been harnessed. Even though there are still challenges that need more work in the areas of patient privacy, Health Insurance Portability and Accountability Act (HIPAA) compliance, reliability, and development of regulatory frameworks, artificial intelligence has revolutionized and will continue to revolutionize medicine.<br><br>SUMMARY: Artificial intelligence is enhancing medical diagnosis and treatment, as well as access and prevention. Ocular imaging, visual outcome, optics, intraocular pressure, and data points will continue to see growth it the field of artificial intelligence.},
}
@article {pmid39606372,
year = {2024},
author = {Gorski, M and Grunin, M and Herold, JM and Fröhlich, B and Behr, M and Wheeler, N and Bush, WS and Song, YE and Zhu, X and Blanton, SH and Pericak-Vance, MA and Heid, IM and Haines, JL and , },
title = {Diverse ancestry GWAS for advanced age-related macular degeneration in TOPMed-imputed and Ophthalmologically-confirmed 16,108 cases and 18,038 controls.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.08.24316962},
pmid = {39606372},
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness with $344 billion dollars global costs. In 2016, the International Age-related Macular Degeneration Genomics Consortium devised genomic data on ∼50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD in European ancestry. We have now analyzed a more densely imputed version (IAMDGC 2.0) and performed cross-ancestry GWAS in 16,108 advanced AMD cases and 18,038 AMD-free controls. This identified 28 loci at P<5×10 [-8] , including two additional AMD loci compared to IAMDGC 1.0 (SERPINA1 and CPN1). Fine-mapping supported one ancestry-shared signal around HTRA1/ARMS2 and nine signals around CFH without African ancestry contribution. The 52-variant genetic risk score with and the 44-variant score without CFH -variants predicted advanced AMD not only in EUR, but also in AFR and ASN (AUC=0.80/0.75, 0.65/0.64, 0.80/0.79, respectively). Our results indicate that the genetic underpinning of advanced AMD is mostly shared between ancestries.},
}
@article {pmid39606340,
year = {2024},
author = {Reeve, MP and Loomis, S and Nissilä, E and Rausch, T and Zheng, Z and Briotta Parolo, PD and Ben-Isvy, D and Aho, E and Cesetti, E and Okunuki, Y and McLaughlin, H and Mäkelä, J and , and Kurki, M and Talkowski, ME and Korbel, JO and Connor, K and Meri, S and Daly, MJ and Runz, H},
title = {Loss of CFHR5 function reduces the risk for age-related macular degeneration.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39606340},
support = {R01 MH115957/MH/NIMH NIH HHS/United States ; R56 MH115957/MH/NIMH NIH HHS/United States ; T32 HG002295/HG/NHGRI NIH HHS/United States ; U24 HG011450/HG/NHGRI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent cause of vision loss in the elderly with limited therapeutic options. A single chromosomal region around the complement factor H gene (CFH) is reported to explain nearly 25% of genetic AMD risk. Here, we used association testing, statistical finemapping and conditional analyses in 12,495 AMD cases and 461,686 controls to deconvolute four major CFH haplotypes that convey protection from AMD. We show that beyond CFH, two of these are explained by Finn-enriched frameshift and missense variants in the CFH modulator CFHR5. We demonstrate through a FinnGen sample recall study that CFHR5 variant carriers exhibit dose-dependent reductions in serum levels of the CFHR5 gene product FHR-5 and two functionally related proteins at the locus. Genetic reduction in FHR-5 correlates with higher preserved activities of the classical and alternative complement pathways. Our results propose therapeutic downregulation of FHR-5 as promising to prevent or treat AMD.},
}
@article {pmid39605874,
year = {2025},
author = {Ehlers, JP and Hu, A and Boyer, D and Cousins, SW and Waheed, NK and Rosenfeld, PJ and Brown, D and Kaiser, PK and Abbruscato, A and Gao, G and Heier, J and , },
title = {ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100628},
pmid = {39605874},
issn = {2666-9145},
abstract = {OBJECTIVE: This study evaluated the safety and efficacy of elamipretide in dry age-related macular degeneration (AMD) with noncentral geographic atrophy (GA).<br><br>DESIGN: ReCLAIM-2 was a prospective, phase II, randomized, placebo-controlled, double-masked, multicenter trial (NCT03891875).<br><br>SUBJECTS: Patients aged &#x2265;55 years with &#x2265;1 eye with dry AMD with GA were enrolled.<br><br>METHODS: Administration of daily subcutaneous elamipretide 40 mg was investigated in subjects for 48 weeks followed by a 4-week follow-up period.<br><br>MAIN OUTCOME MEASURES: The primary efficacy end points were the mean change from baseline (BL) in low-luminance best-corrected visual acuity (LL BCVA) and the change in square root (Sqrt) converted GA area from BL as measured by OCT. Additional predefined end points included ellipsoid zone (EZ) integrity preservation assessment and categorical changes in LL BCVA. The primary safety end point was the incidence and severity of adverse events.<br><br>RESULTS: Of the 176 patients randomized, there were 117 and 59 patients in the elamipretide and placebo groups, respectively. Although elamipretide did not meet statistical significance for the primary end points (mean change in LL BCVA and mean change in Sqrt converted GA area), elamipretide produced a 43% reduction in the mean progression from BL in the macular percentage of total EZ attenuation/loss (i.e., complete loss of EZ band; nominal P&#xa0;=&#xa0;0.0034) and 47% reduction in the mean progression of macular percentage of partial EZ attenuation/degradation (i.e., EZ-retinal pigment endothelium thickness of &#x2264;20 microns; nominal P&#xa0;=&#xa0;0.0040) versus placebo at week 48. Elamipretide treatment was also associated with significantly more patients experiencing a &#x2265;10 letter gain in LL BCVA versus placebo (14.6% vs. 2.1%; nominal P&#xa0;=&#xa0;0.0404). Adverse events were reported in 86% of those receiving elamipretide and 71% of the placebo group with the most common events being injection site reactions (e.g., pruritus, injection site pain, bruising, and erythema).<br><br>CONCLUSIONS: While the primary end points were not met in this phase II study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage. These findings have important clinical relevance since EZ attenuation/photoreceptor loss precedes and predicts the progressive pathological changes associated with vision loss and AMD. The EZ attenuation/loss end point will serve as the regulatory approved primary end point in the elamipretide phase III clinical development program.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39604206,
year = {2025},
author = {Thomsen, AK and Fasih-Ahmad, S and Sadda, S and Sørensen, TL},
title = {Initial treatment response can predict one-year treatment outcomes in neovascular age-related macular degeneration treated according to the observe-and-plan regimen.},
journal = {Acta ophthalmologica},
volume = {103},
number = {3},
pages = {304-312},
doi = {10.1111/aos.16801},
pmid = {39604206},
issn = {1755-3768},
support = {R29-A1337//Region Zealand/ ; 00024226//Velux Fonden/ ; },
mesh = {Humans ; Female ; Male ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Prospective Studies ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; Follow-Up Studies ; Aged ; Treatment Outcome ; Fluorescein Angiography/methods ; *Ranibizumab/administration &amp; dosage ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Fundus Oculi ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Macula Lutea/pathology ; },
abstract = {PURPOSE: To investigate if the initial treatment response can predict the 1-year treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated according to the observe-and-plan (O&amp;P) regimen.<br><br>METHODS: In this prospective cohort study, treatment-na&#xef;ve patients with nAMD were enrolled consecutively and followed for 1&#x2009;year while being treated according to the O&amp;P regimen. The treatment response was determined initially post-loading doses and after 1&#x2009;year. The functional treatment response (fTR) was determined by the change in best corrected visual acuity, while the morphological treatment response (mTR) was assessed by central retinal thickness and the presence of sub- and intraretinal fluid on optical coherence tomography and categorized as good, partial, and poor responders. The relative risk (RR) of the initial treatment response for predicting 1-year treatment response was assessed.<br><br>RESULTS: One hundred patients were included and 94 completed the 1-year follow-up. Patients with an initial good fTR and initial poor fTR had an RR of 4.1 (95% CI 1.8-9.2) and 4.3 (95% CI 2.2-8.3), respectively, of remaining in the same response category at 1&#x2009;year. Similarly, patients with an initial good mTR and initial poor mTR had an RR of 3.0 (95% CI 1.8-4.8) and 8.7 (95% CI 3.0-25.1), respectively, of remaining in the same response category at 1&#x2009;year.<br><br>CONCLUSIONS: Both the anatomic and visual functional response after 3 loading doses are predictive of the anatomic and functional outcomes at 1&#x2009;year in patients with nAMD treated according to the O&amp;P regimen.},
}
@article {pmid39604117,
year = {2025},
author = {Narasimhan, A and Min, SH and Johnson, LL and Roehrich, H and Cho, W and Her, TK and Windschitl, C and O'Kelly, RD and Angelini, L and Yousefzadeh, MJ and McLoon, LK and Hauswirth, WW and Robbins, PD and Skowronska-Krawczyk, D and Niedernhofer, LJ},
title = {The Ercc1[-/Δ] mouse model of XFE progeroid syndrome undergoes accelerated retinal degeneration.},
journal = {Aging cell},
volume = {24},
number = {3},
pages = {e14419},
pmid = {39604117},
issn = {1474-9726},
support = {P30 EY034070/EY/NEI NIH HHS/United States ; U54AG079754//Common Fund/ ; P30EY034070//Common Fund/ ; U19AG056278//Common Fund/ ; U19 AG056278/AG/NIA NIH HHS/United States ; R01AG063543//Common Fund/ ; U01EY034594//Common Fund/ ; },
mesh = {Animals ; *DNA-Binding Proteins/genetics/metabolism/deficiency ; *Endonucleases/genetics/metabolism/deficiency ; Mice ; Disease Models, Animal ; *Retinal Degeneration/pathology/genetics/metabolism ; DNA Damage ; Retinal Pigment Epithelium/pathology/metabolism ; Retina/pathology/metabolism ; Humans ; *Progeria/genetics/pathology ; Macular Degeneration/pathology/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of vision loss in older adults. AMD is caused by degeneration in the macula of the retina. The retina is the highest oxygen consuming tissue in our body and is prone to oxidative damage. DNA damage is one hallmark of aging implicated in loss of organ function. Genome instability has been associated with several disorders that result in premature vision loss. We hypothesized that endogenous DNA damage plays a causal role in age-related retinal changes. To address this, we used a genetic model of systemic depletion of expression of the DNA repair enzyme ERCC1-XPF. The neural retina and retinal pigment epithelium (RPE) from Ercc1[-/Δ] mice, which models a human progeroid syndrome, were compared to age-matched wild-type (WT) and old WT mice. By 3-months-of age, Ercc1[-/Δ] mice presented abnormal optokinetic and electroretinogram responses consistent with photoreceptor dysfunction and visual impairment. Ercc1[-/Δ] mice shared many ocular characteristics with old WT mice including morphological changes, elevated DNA damage markers (γ-H2AX and 53BP1), and increased cellular senescence in the neural retinal and RPE, as well as pathological angiogenesis. The RPE is essential for the metabolic health of photoreceptors. The RPE from Ercc1[-/Δ] mice displayed mitochondrial dysfunction causing a compensatory glycolytic shift, a characteristic feature of aging RPE. Hence, our study suggests spontaneous endogenous DNA damage promotes the hallmarks of age-related retinal degeneration.},
}
@article {pmid39603590,
year = {2025},
author = {Antropoli, A and Bianco, L and Romano, F and Trinco, A and Arrigo, A and Benadji, A and Atia, R and Palacci, O and Dagostinoz, D and Devisme, C and Condroyer, C and Antonio, A and Bosello, F and Casati, S and Salvetti, AP and Zaffalon, C and Gaudric, A and Sahel, JA and Staurenghi, G and Bandello, F and Sennlaub, F and Zeitz, C and Meunier, I and Battaglia Parodi, M and Audo, I},
title = {Extensive macular atrophy with pseudodrusen-like appearance (EMAP) clinical characteristics, diagnostic criteria, and insights from allied inherited retinal diseases and age-related macular degeneration.},
journal = {Progress in retinal and eye research},
volume = {104},
number = {},
pages = {101320},
doi = {10.1016/j.preteyeres.2024.101320},
pmid = {39603590},
issn = {1873-1635},
mesh = {Humans ; Fluorescein Angiography/methods ; Macula Lutea/pathology ; *Macular Degeneration/complications/diagnosis/genetics ; *Retinal Drusen/complications/diagnosis/genetics ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; },
abstract = {Extensive macular atrophy with pseudodrusen-like appearance (EMAP) was first described in France in 2009 as a symmetric and rapidly progressive form of macular atrophy primarily affecting middle-aged individuals. Despite the recent identification of a significant number of cases in Italy and worldwide, EMAP remains an underrecognized condition. The clinical triad typical of EMAP consists of vertically oriented macular atrophy with multilobular borders, pseudodrusen-like deposits across the posterior pole and mid-periphery, and peripheral pavingstone degeneration. Nonetheless, recent research has portrayed EMAP as a highly stage-dependent condition, allowing the identification of novel disease hallmarks, including a diffuse separation between the Bruch's membrane and the retinal pigment epithelium, along with consistent sparing of a region temporal to the macula. Additionally, retinal electrophysiology is particularly useful in distinguishing EMAP from age-related macular degeneration (AMD). Supported by unpublished data from the largest EMAP cohorts worldwide, this review aims to provide a comprehensive and updated description of EMAP, now recognized as a severely blinding disease characterized by diffuse chorioretinal atrophy and photoreceptor dysfunction. Furthermore, we propose a set of diagnostic criteria that incorporate clinical, imaging, and functional tests, to facilitate the recognition of this clinical entity. Lastly, we aim to shed light on its pathogenesis by comparing it with AMD and monogenic retinal disorders exhibiting similar phenotypes.},
}
@article {pmid39603315,
year = {2025},
author = {Bennett, C and Romano, F and Vingopoulos, F and Garcia, M and Ding, X and Bannerman, A and Ploumi, I and Ntentakis, D and Stettler, I and Overbey, K and Baldwin, G and Bejjani, R and Garg, I and Rodriguez, J and Laìns, I and Kim, LA and Vavvas, D and Husain, D and Miller, JW and Miller, JB},
title = {Associations Between Contrast Sensitivity, Optical Coherence Tomography Features and Progression From Intermediate to Late Age-related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {271},
number = {},
pages = {175-187},
doi = {10.1016/j.ajo.2024.11.006},
pmid = {39603315},
issn = {1879-1891},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Cross-Sectional Studies ; Male ; Aged ; *Contrast Sensitivity/physiology ; Disease Progression ; Visual Acuity/physiology ; Follow-Up Studies ; *Wet Macular Degeneration/physiopathology/diagnosis ; Aged, 80 and over ; *Macular Degeneration/physiopathology/diagnosis ; Retinal Pigment Epithelium/pathology ; Fluorescein Angiography ; },
abstract = {PURPOSE: Establishing associations between structure, function, and clinical outcomes in intermediate age-related macular degeneration (iAMD) remains an unmet need. This study aims to (1) cross-sectionally investigate the relationships between optical coherence tomography (OCT) biomarkers and quantitative contrast sensitivity function (qCSF)-measured contrast sensitivity (CS), and (2) longitudinally assess their relationship with progression from iAMD to late stages of the disease.<br><br>DESIGN: Cross-sectional and cohort study.<br><br>METHODS: Our study was conducted at Massachusetts Eye and Ear (Boston, MA, USA) and included eyes with (1) baseline diagnosis of iAMD, (2) same-day OCT and qCSF test, (3) visual acuity &#x2265;20/200 Snellen, and (4) 24+ months of follow-up. qCSF metrics included the area under the logCSF curve, contrast acuity, and CS thresholds at 1- to 18-cycle-per-degree (cpd). Two independent graders reviewed macular OCT scans for various biomarkers, and outer nuclear layer (ONL) thickness and retinal pigment epithelium (RPE) volume were measured. Progression to wet AMD or geographic atrophy (GA) was confirmed using imaging studies. Generalized linear mixed-effects models assessed associations between qCSF and OCT biomarkers, while Cox regression models evaluated their association with progression to late AMD.<br><br>RESULTS: We included 205 iAMD eyes from 134 patients (age: 73 [69-78] years; 63% female). Higher RPE volume in the central subfield and a greater number of intraretinal hyperreflective foci were associated with reduced area under the logCSF curve, contrast acuity, and CS at 6 to 12 cpd (P < .05). ONL thinning in the inner ring and a greater number of intraretinal hyperreflective foci were associated with reduced CS at 1 and 3 cpd (P < .05). During follow-up, 35 eyes developed wet AMD (17%) and 53 progressed to GA (26%). subretinal drusenoid deposit, ONL thinning in the inner ring, and reduced CS at 1.5 cpd were associated with wet AMD (P < .05). Higher RPE volume in the inner ring, hyporeflective drusen cores, subretinal drusenoid deposit, higher HRF count, and reduced CS at 1 cpd were associated with GA (P < .05).<br><br>CONCLUSIONS: Our study reveals significant structure-function relationships between OCT biomarkers and qCSF-measured CS in iAMD. These findings highlight the impact of AMD alterations on CS function and offer valuable insights for patient stratification and prognostication in research and clinical settings.},
}
@article {pmid39602510,
year = {2024},
author = {O'Hare, M and Miller, WP and Arevalo-Alquichire, S and Amarnani, D and Apryani, E and Perez-Corredor, P and Marino, C and Shu, DY and Vanderleest, TE and Muriel-Torres, A and Gordon, HB and Gunawan, AL and Kaplan, BA and Barake, KW and Bejjani, RP and Doan, TH and Lin, R and Delgado-Tirado, S and Gonzalez-Buendia, L and Rossin, EJ and Zhao, G and Eliott, D and Weinl-Tenbruck, C and Chevessier-Tünnesen, F and Rejman, J and Montrasio, F and Kim, LA and Arboleda-Velasquez, JF},
title = {An mRNA-encoded dominant-negative inhibitor of transcription factor RUNX1 suppresses vitreoretinal disease in experimental models.},
journal = {Science translational medicine},
volume = {16},
number = {775},
pages = {eadh0994},
doi = {10.1126/scitranslmed.adh0994},
pmid = {39602510},
issn = {1946-6242},
mesh = {Animals ; *Core Binding Factor Alpha 2 Subunit/metabolism/genetics ; Rabbits ; Humans ; *RNA, Messenger/metabolism/genetics ; *Disease Models, Animal ; *Vitreoretinopathy, Proliferative/pathology/metabolism ; Mice ; Nanoparticles/chemistry ; Cell Proliferation ; },
abstract = {Messenger RNA (mRNA)-based therapies are a promising approach to medical treatment. Except for infectious diseases, no other disease has mRNA-based therapies available. The eye is an ideal model for mRNA therapeutic development because it requires limited dosing. Proliferative vitreoretinopathy (PVR) is a blinding condition caused by retinal detachment that now lacks available medical treatment, with surgery as the only treatment option. We previously implicated runt-related transcription factor-1 (RUNX1) as a driver of epithelial-to-mesenchymal transition (EMT) in PVR and as a critical mediator of aberrant ocular angiogenesis when up-regulated. On the basis of these findings, an mRNA was designed to express a dominant-negative inhibitor of RUNX1 (RUNX1-Trap). We show that RUNX1-Trap delivered in polymer-lipidoid complexes or lipid nanoparticles sequestered RUNX1 in the cytosol and strongly reduced proliferation in primary cell cultures established from fibrotic membranes derived from patients with PVR. We assessed the preclinical efficacy of intraocular delivery of mRNA-encoded RUNX1-Trap in a rabbit model of PVR and in a laser-induced mouse model of aberrant angiogenesis often used to study wet age-related macular degeneration. mRNA-encoded RUNX1-Trap suppressed ocular pathology, measured as pathological scores in the rabbit PVR model and leakage and lesion size in the laser-induced choroidal neovascularization mouse model. mRNA-encoded RUNX1-Trap also strongly reduced proliferation in a human ex vivo explant model of PVR. These data demonstrate the therapeutic potential of mRNA-encoded therapeutic molecules with dominant-negative properties, highlighting the potential of mRNA-based therapies beyond standard gene supplementation approaches.},
}
@article {pmid39602505,
year = {2024},
author = {Mori, T and Kumar R N, N and Ferrara, N},
title = {Elucidating VEGF Biology: A Journey of Discovery and Clinical Translation.},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
volume = {44},
number = {12},
pages = {2361-2365},
pmid = {39602505},
issn = {1524-4636},
support = {R01 EY031345/EY/NEI NIH HHS/United States ; },
}
@article {pmid39601967,
year = {2024},
author = {Tzaridis, S and Aguilar, E and Dorrell, MI and Friedlander, M and Eade, KT},
title = {Retinal pigment epithelial cells reduce vascular leak and proliferation in retinal neovessels.},
journal = {Angiogenesis},
volume = {28},
number = {1},
pages = {1},
pmid = {39601967},
issn = {1573-7209},
mesh = {Animals ; *Retinal Pigment Epithelium/pathology/metabolism ; *Cell Proliferation ; Mice ; Humans ; *Receptors, LDL/genetics/metabolism/deficiency ; Epithelial-Mesenchymal Transition ; Mice, Knockout ; Retinal Vessels/pathology/metabolism ; Retrospective Studies ; Retinal Neovascularization/pathology/metabolism ; Male ; Cell Movement ; Mice, Inbred C57BL ; Retinal Telangiectasis/pathology/metabolism ; },
abstract = {In multiple neurodegenerative diseases, including age-related macular degeneration, retinitis pigmentosa, and macular telangiectasia type 2 (MacTel), retinal pigment epithelial (RPE)-cells proliferate and migrate into the neuroretina, forming intraretinal pigment plaques. Though these pigmentary changes are hallmarks of disease progression, it is unknown if their presence is protective or detrimental.Here, we first evaluated the impact of pigment plaques on vascular changes and disease progression in MacTel. In a retrospective, longitudinal study, we analyzed multimodal retinal images of patients with MacTel and showed that pigment plaques were associated with decreased vascular leakage and stabilized neovascular growth. We then modeled the underlying pathomechanisms of pigment plaque formation in aberrant neovascular growth using the very-low-density lipoprotein receptor mutant (Vldlr[-/-]) mouse. Our data indicated that during RPE-proliferation, migration and accumulation along neovessels RPE-cells underwent epithelial-mesenchymal transition (EMT). Pharmacologic inhibition of EMT in Vldlr[-/-] mice decreased pigment coverage, and exacerbated neovascular growth and vascular leakage.Our findings indicate that the proliferation, migration and perivascular accumulation of RPE-cells stabilize vascular proliferation and exudation, thereby exerting a protective effect on the diseased retina. We conclude that interfering with this "natural repair mechanism" may have detrimental effects on the course of the disease and should thus be avoided.},
}
@article {pmid39601844,
year = {2025},
author = {Furundaoturan, O and Degirmenci, C and Afrashi, F and Atik, T and Akkin, C and Mentes, J and Nalcaci, S},
title = {Association between the ARMS2 rs10490924 risk genotype and dry-age related macular degeneration patients with and without reticular pseudodrusen in a Turkish population: findings from a study conducted at a tertiary clinic.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {4},
pages = {1167-1173},
pmid = {39601844},
issn = {1435-702X},
support = {TTU-2021-28871//Ege University Research Foundation/ ; },
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; Tomography, Optical Coherence/methods ; Aged ; Turkey/epidemiology ; *Proteins/genetics/metabolism ; Fluorescein Angiography/methods ; Genotype ; Middle Aged ; *Geographic Atrophy/genetics/diagnosis/epidemiology/complications ; *Retinal Drusen/genetics/diagnosis/epidemiology ; *Polymorphism, Single Nucleotide ; *DNA/genetics ; *Tertiary Care Centers ; Fundus Oculi ; Alleles ; Genetic Predisposition to Disease ; Aged, 80 and over ; Risk Factors ; Incidence ; },
abstract = {PURPOSE: To evaluate the relationship between the presence of reticular pseudodrusen (RPD) and the risk allele of ARMS2 rs10490924 variation in dry-AMD patients by using multimodal imaging. Also, to compare patients with and without RPD and healthy volunteers according to the distribution of the risk allele.<br><br>METHODS: In this cross-sectional study, dry-AMD patients with (Group A,&#xa0;n&#x2009;=&#x2009;50) and without (Group B,&#xa0;n&#x2009;=&#x2009;50) RPD and healthy volunteers (Group C,&#xa0;n&#x2009;=&#x2009;50) were enrolled. After detailed ophthalmologic examination, confocal scanning laser ophthalmoscope (Heidelberg, Germany) was used to acquire near infra-red (NIR) imaging for RPD and the diagnosis was confirmed by Spectral Domain-Optical coherence tomography (Heidelberg, Germany). In silent choroidal neovascularization suspicion, optical coherence tomography angiography (Optovue, Fremont, CA) was performed and those were excluded. For genetic assessment, peripheric blood sampling was performed. Using next-generation sequencing technique (NGS), ARMS2 rs10490924 single nucleotide polymorphism was investigated. Groups were compared according to the distribution of the risky allele.<br><br>RESULTS: 150 eyes of 150 participants were included. In Group A, 42% (21) of patients were heterozygous for the T risk allele, 30% (15) were homozygous, and the risk allele was not detected in 28% (14). In Group B, 44% (22) of patients were heterozygous, 17% (8) were homozygous, and the risk allele was not detected in 39% (20). In Group C, 30% (15) of participants were heterozygous, 4% (2) were homozygous, and variation was not observed in 64% (32). Homozygous participants in Group A were significantly higher than other two groups (Group A-B: OR&#x2009;=&#x2009;2.67, 95% CI: 0.895, 8.020; Group A-C: OR&#x2009;=&#x2009;17.14, 95% CI: 3.449, 85.208) while in Group B, homozygous individuals were higher than Group C (respectively, p values 0.0039, 0.0002, 0.013). T risky allele frequencies were 51%, 38%, and 20% in Groups A, B, and C, respectively, which was significantly higher in Group A (p&#x2009;=&#x2009;0.02).<br><br>CONCLUSION: Genetic influence in AMD is inevitable while certain differences according to different ethnicities may apply. Association of genetic variations and imaging findings like RPD is lacking among literature for different populations. By the aspect of this study, the relationship between RPD and ARMS2 rs10490924 polymorphism in dry-AMD patients were highlighted among Turkish population by using multimodal imaging for the first time.<br><br>KEY MESSAGES: What is Known? Pathophysiology of age-related macular degeneration is influenced from multiple factors including single nucleotide polymorphisms. The variations of ARMS2 are suspected well in the current literature. Reticular pseudodrusen is related to advanced stages of age related macular degeneration disease. What is New? The ARMS2 rs10490924 risk genotype is associated with the presence of reticular pseudodrusen in dry&#xa0;age related macular degeneration patients. Homozygous genotype of T risk allele is evaluated significantly higher in dry age related macular degeneration patients&#xa0;with reticular pseudodrusen.},
}
@article {pmid39600369,
year = {2024},
author = {Wang, H and Zheng, J and Zhang, Q and Tian, Z and Sun, Y and Zhu, T and Bi, Y and Zhang, L},
title = {Efficacy and safety of complement inhibitors in patients with geographic atrophy associated with age-related macular degeneration: a network meta-analysis of randomized controlled trials.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1410172},
pmid = {39600369},
issn = {1663-9812},
abstract = {IMPORTANCE: Clinical trials in recent years have shown significant effectiveness of complement inhibitors for geographic atrophy (GA) treatment. Two complement inhibitor drugs have been approved by the Food and Drug Administration (FDA).<br><br>OBJECTIVE: to compare and rank the different complement inhibitors in the treatment of GA secondary to age-related macular degeneration (AMD).<br><br>DATA SOURCES: A systematic literature search was conducted in the Cochrane Central, Web of Science Core Collection, PubMed, LWW Medical Journals, ClinicalTrials.gov, and WHO ICTRP from inception to October 2023.<br><br>STUDY SELECTION: All randomized clinical trials evaluating the effectiveness of complement inhibitors in patients diagnosed with secondary GA in AMD were identified.<br><br>DATA EXTRACTION AND SYNTHESIS: This study followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) network meta-analysis Checklist of Items and the Cochrane Risk of Bias Assessment Tool for assessing the study quality. Multiple authors independently coded all titles and abstracts, reviewed full-text articles against the inclusion and exclusion criteria, and resolved all discrepancies by consensus. Random-effects network meta-analyses were applied. Bayesian network meta-analysis was performed using the BUGSnet package in R (4.2.0).<br><br>MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the change in GA lesion size (mm[2]) from baseline to month 12. The secondary efficacy outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to month 12. Safety outcome measures included the number of subjects with serious adverse events (SAEs) and macular neovascularization (MNV).<br><br>RESULTS: Ten randomized controlled trials including 4,405 participants and five complement inhibitors were identified. Comparison with sham and SUCRA analysis showed that avacincaptad pegol 2&#xa0;mg (MD: -0.58, 95% CrI: -0.97 to -0.18, SUCRA: 93.55), pegcetacoplan monthly (MD: -0.38, 95% CrI: -0.57 to -0.20, SUCRA: 81.37), and pegcetacoplan every other month (MD: -0.30, 95% CrI: -0.49 to -0.11, SUCRA: 70.16) have significant changes in GA lesion reduction. No treatments showed significant changes in BCVA and SAE compared with sham. Pegcetacoplan monthly (OR: 4.30, 95% CrI: 1.48-16.72) increased the risk of MNV. Avacincaptad pegol 2&#xa0;mg demonstrated favorable outcomes in terms of SAE and MNV.<br><br>CONCLUSION AND RELEVANCE: Avacincaptad pegol 2&#xa0;mg is the most effective complement inhibitor with better safety for the treatment of GA secondary to AMD.<br><br>https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351515, Identifier PROSPERO CRD42022351515.},
}
@article {pmid39599758,
year = {2024},
author = {Baldi, S and Pagliai, G and Di Gloria, L and Pallecchi, M and Barca, F and Pieri, B and Bartolucci, G and Ramazzotti, M and Amedei, A and Palendri, G and Sofi, F},
title = {Beneficial Effects of Micronutrient Supplementation in Restoring the Altered Microbiota and Gut-Retina Axis in Patients with Neovascular Age-Related Macular Degeneration-A Randomized Clinical Trial.},
journal = {Nutrients},
volume = {16},
number = {22},
pages = {},
pmid = {39599758},
issn = {2072-6643},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Dietary Supplements ; *Micronutrients/pharmacology ; Male ; Aged ; Female ; *Macular Degeneration/drug therapy ; Retina/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Lutein/pharmacology/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Visual Acuity/drug effects ; Crocus/chemistry ; Zeaxanthins/pharmacology ; },
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.},
}
@article {pmid39598522,
year = {2024},
author = {Rojekar, S and Parit, S and Gholap, AD and Manchare, A and Nangare, SN and Hatvate, N and Sugandhi, VV and Paudel, KR and Ingle, RG},
title = {Revolutionizing Eye Care: Exploring the Potential of Microneedle Drug Delivery.},
journal = {Pharmaceutics},
volume = {16},
number = {11},
pages = {},
pmid = {39598522},
issn = {1999-4923},
abstract = {Microneedle technology revolutionizes ocular drug delivery by addressing challenges in treating ocular diseases. This review explores its potential impact, recent advancements, and clinical uses. This minimally invasive technique offers precise control of drug delivery to the eye, with various microneedle types showing the potential to penetrate barriers in the cornea and sclera, ensuring effective drug delivery. Recent advancements have improved safety and efficacy, offering sustained and controlled drug delivery for conditions like age-related macular degeneration and glaucoma. While promising, challenges such as regulatory barriers and long-term biocompatibility persist. Overcoming these through interdisciplinary research is crucial. Ultimately, microneedle drug delivery presents a revolutionary method with the potential to significantly enhance ocular disease treatment, marking a new era in eye care.},
}
@article {pmid39598433,
year = {2024},
author = {Emeka, PM and Badger-Emeka, LI and Thirugnanasambantham, K and Alatawi, AS},
title = {Rutin-Activated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Attenuates Corneal and Heart Damage in Mice.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {11},
pages = {},
pmid = {39598433},
issn = {1424-8247},
support = {KSRG-2023-107//King Salman Center for Disability Research/ ; },
abstract = {Background: Corneal degeneration is a form of progressive cell death caused by multiple factors, such as diabetic retinopathy. It is the most well-known neural degenerative disease caused by macular degeneration in the aged and those with retinitis pigmentosa. Myocardial infarction is becoming a more common burden, causing cardiomyocyte degeneration, ischemia, and heart tissue death. This study examined the preventive effects of rutin on isoproterenol (ISO)-induced oxidative damage (that is, inflammation) on rabbit corneal epithelial cells and mouse heart injuries. Methods: These investigations involved a cytotoxicity test, biochemical analysis, qRT-PCR, Western blotting, and mouse cardiac histopathology. Results: The results showed that rutin enhanced ADH7 and ALDH1A1, retinoic acid signaling components in SIRC1 rabbit corneal cell lines. The production of NO by ocular epithelial cells was significantly reduced. It reduced cTnT and cTnI, CK-MB, and LDH contents in mouse cardiac tissue. The nuclear expressions of Nrf2, Sirt, and HO-1 were all increased by rutin. Docking studies revealed a good interaction between rutin and the Keap protein, enhancing Nrf2 nuclear activity. Conclusions: This showed that rutin can potentially enhance ADH7 and ALDH1A1 corneal signaling components, preventing corneal degeneration and mitigating ISO-induced myocardial infarction (MI) via Keap/Nrf2 expressions.},
}
@article {pmid39598352,
year = {2024},
author = {Sorrentino, FS and Zeppieri, M and Culiersi, C and Florido, A and De Nadai, K and Adamo, GG and Pellegrini, M and Nasini, F and Vivarelli, C and Mura, M and Parmeggiani, F},
title = {Application of Artificial Intelligence Models to Predict the Onset or Recurrence of Neovascular Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {11},
pages = {},
pmid = {39598352},
issn = {1424-8247},
abstract = {Neovascular age-related macular degeneration (nAMD) is one of the major causes of vision impairment that affect millions of people worldwide. Early detection of nAMD is crucial because, if untreated, it can lead to blindness. Software and algorithms that utilize artificial intelligence (AI) have become valuable tools for early detection, assisting doctors in diagnosing and facilitating differential diagnosis. AI is particularly important for remote or isolated communities, as it allows patients to endure tests and receive rapid initial diagnoses without the necessity of extensive travel and long wait times for medical consultations. Similarly, AI is notable also in big hubs because cutting-edge technologies and networking help and speed processes such as detection, diagnosis, and follow-up times. The automatic detection of retinal changes might be optimized by AI, allowing one to choose the most effective treatment for nAMD. The complex retinal tissue is well-suited for scanning and easily accessible by modern AI-assisted multi-imaging techniques. AI enables us to enhance patient management by effectively evaluating extensive data, facilitating timely diagnosis and long-term prognosis. Novel applications of AI to nAMD have focused on image analysis, specifically for the automated segmentation, extraction, and quantification of imaging-based features included within optical coherence tomography (OCT) pictures. To date, we cannot state that AI could accurately forecast the therapy that would be necessary for a single patient to achieve the best visual outcome. A small number of large datasets with high-quality OCT, lack of data about alternative treatment strategies, and absence of OCT standards are the challenges for the development of AI models for nAMD.},
}
@article {pmid39596978,
year = {2024},
author = {Ong, J and Chhablani, J},
title = {Advances in Imaging-Based Machine Learning and Therapeutic Technology in the Management of Retinal Diseases.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {11},
pages = {},
pmid = {39596978},
issn = {1648-9144},
mesh = {Humans ; *Machine Learning/trends ; *Retinal Diseases/therapy/diagnostic imaging ; Central Serous Chorioretinopathy/diagnostic imaging ; },
abstract = {Retinal conditions like age-related macular degeneration (AMD), diabetic retinopathy, central serous chorioretinopathy (CSCR), and retinal vein occlusion can drastically affect a patient's quality of life [...].},
}
@article {pmid39595533,
year = {2024},
author = {Wróblewska, J and Nuszkiewicz, J and Wróblewski, M and Wróblewska, W and Woźniak, A},
title = {Selected Trace Elements and Their Impact on Redox Homeostasis in Eye Health.},
journal = {Biomolecules},
volume = {14},
number = {11},
pages = {},
pmid = {39595533},
issn = {2218-273X},
mesh = {Humans ; *Trace Elements/metabolism ; *Oxidation-Reduction ; *Oxidative Stress ; *Homeostasis ; *Antioxidants/metabolism ; Animals ; Eye/metabolism ; Eye Diseases/metabolism ; Reactive Oxygen Species/metabolism ; },
abstract = {Oxidative stress plays a crucial role in the pathogenesis of various ocular degenerative diseases, leading to structural and functional changes in eye tissues. This imbalance between reactive oxygen species (ROS) and antioxidants significantly contributes to conditions such as age-related macular degeneration, diabetic retinopathy, cataracts, and glaucoma. Both enzymatic and nonenzymatic antioxidants are vital for maintaining ocular health by neutralizing ROS and restoring cellular redox balance. Essential trace elements, including iron, zinc, copper, and selenium, are fundamental for the proper functioning of these antioxidant systems. Iron is indispensable for enzymatic activity and cellular energy production, zinc supports numerous proteins involved in visual functions and antioxidant defense, copper is essential for various enzymatic reactions preventing oxidative stress, and selenium is critical for the activity of antioxidant enzymes such as glutathione peroxidase (GPX) and thioredoxin reductase (TrxR). This review summarizes current research on the complex interactions between oxidative stress and trace elements in ocular diseases, highlighting the therapeutic potential of antioxidant supplementation to mitigate oxidative damage and improve eye health. By integrating insights from studies on oxidative stress, trace elements, and eye physiology, this article underscores new diagnostic and therapeutic strategies that could lead to more effective prevention and treatment of ocular diseases, aiming to enhance clinical outcomes and guide future research in optimizing therapeutic strategies for eye health.},
}
@article {pmid39595213,
year = {2024},
author = {Wu, D and Liu, Y and Luo, X and Chen, Z and Fu, Q and Yao, K},
title = {Involvement of Lgals3/Galectin-3 in Choroidal Neovascularization and Subretinal Fibrosis Formation.},
journal = {Biomedicines},
volume = {12},
number = {11},
pages = {},
pmid = {39595213},
issn = {2227-9059},
support = {LQ21H120003//Zhejiang Provincial Natural Science Foundation of China/ ; 82301207//National Natural Science Foundation of China/ ; 2024ZY01057//Central guidance for local scientific and technological development funding projects/ ; },
abstract = {Background:Lgals3/galectin-3 plays a pivotal role in many vascular diseases. However, the involvement of Lgals3/galectin-3 in eyes with neovascular age-related macular degeneration (nAMD) remains unknown. Methods: In the laser-induced CNV model, a whole mount retina stained with Isolectin B4 and collagen type I revealed the vascular bed and CNV-associated subretinal fibrosis on day 7 after laser treatment. Results: We show that the expression levels of Lgals3/galectin-3 were significantly increased in the RPE/choroidal complex of CNV mice. An intravitreal injection of Lgals3-siRNA significantly suppressed the area of CNV and subretinal fibrosis, together with Mcp-1 decline. The mixture of Lgals3-siRNA and Ranibizumab showed more efficiency than each drug used separately. Hypoxia induced Lgals3/galectin-3 production in ARPE-19 cells, which was reduced by the silencing hypoxia-inducible factor -1α (Hif-1a). Conclusions: Our data indicated that Lgals3/galectin-3 is involved in the pathogenesis of CNV and subretinal fibrosis, and Lgals3/galectin-3 could be a potential therapeutic target for nAMD.},
}
@article {pmid39594655,
year = {2024},
author = {Catral, KPC and Tse, CY and Yang, WY and Ling, CY and Kwok, OL and Choy, KY and Lu, DQ and Bian, JF and Lam, TC and Tse, DY and Shan, SS},
title = {Thrombospondin 1 Mediates Autophagy Upon Inhibition of the Rho-Associated Protein Kinase Inhibitor.},
journal = {Cells},
volume = {13},
number = {22},
pages = {},
pmid = {39594655},
issn = {2073-4409},
support = {1-BD6R//Hong Kong Polytechnic University/ ; 1-BBDL//Hong Kong Polytechnic University/ ; U-ZEZ2//University Grants Committee (UGC)/ ; The InnoHK initiative of the Hong Kong Special Administrative Region Government//The InnoHK initiative of the Hong Kong Special Administrative Region Government/ ; 08191556//Health and Medical Research Fund/ ; 09200276//Health and Medical Research Fund/ ; 1-BBDA//Research Centre for SHARP Vision/ ; 1-BBC0//Research Centre for SHARP Vision/ ; PolyU Research Postgraduate Studentship//Hong Kong Polytechnic University/ ; },
mesh = {Humans ; *Autophagy/drug effects ; *rho-Associated Kinases/metabolism/antagonists &amp; inhibitors ; *Thrombospondin 1/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/drug effects ; Cell Line ; *Protein Kinase Inhibitors/pharmacology ; Vacuoles/metabolism/drug effects ; Down-Regulation/drug effects ; },
abstract = {Age-related macular degeneration (AMD) is a degenerative eye disease leading to central vision loss and is characterized by dysregulated autophagy of the retinal pigment epithelium (RPE) layer. Recent studies have suggested that rho-associated protein kinase (ROCK) inhibitors may enhance autophagy in neurodegenerative diseases and promote the survival of RPE cells. This study investigated the effect of ROCK inhibitors on autophagy gene expression and autophagic vacuole formation in a human RPE (ARPE-19) cell line. The highly selective and potent ROCK inhibitor Y-39983 enhanced the expression of autophagy genes in ARPE-19 cells and increased autophagic vacuole formation. A proteomic analysis using mass spectrometry was performed to further characterize the effects of ROCK inhibition at the protein level. Y-39983 downregulated thrombospondin-1 (THBS1), and suppression of THBS1 in ARPE-19 cells resulted in an increase in autophagic vacuole formation. Our data showed that ROCK inhibitor-induced autophagy was mediated by THBS1 downregulation. We identified ROCK and THBS1 as potential novel therapeutic targets in AMD.},
}
@article {pmid39594569,
year = {2024},
author = {Bakker, LM and Boulton, ME and Różanowska, MB},
title = {(Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {11},
pages = {},
pmid = {39594569},
issn = {2076-3921},
support = {SCIAD 048//National Eye Research Centre/ ; },
abstract = {Docosahexaenoate is a cytoprotective ω-3 polyunsaturated lipid that is abundant in the retina and is essential for its function. Due to its six unsaturated double bonds, docosahexaenoate is highly susceptible to oxidation and the formation of products with photosensitizing properties. This study aimed to test on cultured human retinal pigment epithelial cells ARPE-19 the (photo)cytotoxic potential of partly oxidized docosahexaenoate and its effect on the formation of lipofuscin from phagocytosed photoreceptor outer segments (POSs). The results demonstrate that the cytoprotective effects of docosahexaenoate do not counteract the deleterious effects of its oxidation products, leading to the concentration-dependent loss of cell metabolic activity, which is exacerbated by concomitant exposure to visible light. Partly oxidized docosahexaenoate does not cause permeability of the cell plasma membrane but does cause apoptosis. While vitamin E can provide partial protection from the (photo)toxicity of partly oxidized docosahexaenoate, zeaxanthin undergoes rapid photodegradation and can exacerbate the (photo)toxicity. Feeding cells with POSs enriched in partly oxidized docosahexaenoate results in a greater accumulation of intracellular fluorescent lipofuscin than in cells fed POSs without the addition. In conclusion, partly oxidized docosahexaenoate increases the accumulation of lipofuscin-like intracellular deposits, is cytotoxic, and its toxicity increases during exposure to light. These effects may contribute to the increased progression of geographic atrophy observed after long-term supplementation with docosahexaenoate in age-related macular degeneration patients.},
}
@article {pmid39593115,
year = {2024},
author = {Hogg, HDJ and Brittain, K and Talks, J and Keane, PA and , and Maniatopoulos, G},
title = {Intervention design for artificial intelligence-enabled macular service implementation: a primary qualitative study.},
journal = {Implementation science communications},
volume = {5},
number = {1},
pages = {131},
pmid = {39593115},
issn = {2662-2211},
support = {MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; NIHR301467//Research Trainees Coordinating Centre/ ; MR/T019050/1//UK Research and Innovation/ ; R190028A//Moorfields Eye Charity/ ; },
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is one of the largest single-disease contributors to hospital outpatient appointments. Challenges in finding the clinical capacity to meet this demand can lead to sight-threatening delays in the macular services that provide treatment. Clinical artificial intelligence (AI) technologies pose one opportunity to rebalance demand and capacity in macular services. However, there is a lack of evidence to guide early-adopters seeking to use AI as a solution to demand-capacity imbalance. This study aims to provide guidance for these early adopters on how AI-enabled macular services may best be implemented by exploring what will influence the outcome of AI implementation and why.<br><br>METHODS: Thirty-six semi-structured interviews were conducted with participants. Data were analysed with the Nonadoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework to identify factors likely to influence implementation outcomes. These factors and the primary data then underwent a secondary analysis using the Fit between Individuals, Technology and Task (FITT) framework to propose an actionable intervention.<br><br>RESULTS: nAMD treatment should be initiated at face-to-face appointments with clinicians who recommend year-long periods of AI-enabled scheduling of treatments. This aims to maintain or enhance the quality of patient communication, whilst reducing consultation frequency. Appropriately trained photographers should take on the additional roles of inputting retinal imaging into the AI device and overseeing its communication to clinical colleagues, while ophthalmologists assume clinical oversight and consultation roles. Interoperability to facilitate this intervention would best be served by imaging equipment that can send images to the cloud securely for analysis by AI tools. Picture Archiving and Communication Software (PACS) should have the capability to output directly into electronic medical records (EMR) familiar to clinical and administrative staff.<br><br>CONCLUSION: There are many enablers to implementation and few of the remaining barriers relate directly to the AI technology itself. The proposed intervention requires local tailoring and prospective evaluation but can support early adopters in optimising the&#xa0;chances of success from initial efforts to implement AI-enabled macular services.<br><br>PROTOCOL REGISTRATION: Hogg HDJ, Brittain K, Teare D, Talks J, Balaskas K, Keane P, Maniatopoulos G. Safety and efficacy of an artificial intelligence-enabled decision tool for treatment decisions in neovascular age-related macular degeneration and an exploration of clinical pathway integration and implementation: protocol for a multi-methods validation study. BMJ Open. 2023 Feb 1;13(2):e069443. https://doi.org/10.1136/bmjopen-2022-069443 . PMID: 36725098; PMCID: PMC9896175.},
}
@article {pmid39589947,
year = {2024},
author = {Dinarvand, D and Panthakey, J and Hassan, A and Ahmed, MH},
title = {Frailty and Visual Impairment in Elderly Individuals: Improving Outcomes and Modulating Cognitive Decline Through Collaborative Care Between Geriatricians and Ophthalmologists.},
journal = {Diseases (Basel, Switzerland)},
volume = {12},
number = {11},
pages = {},
pmid = {39589947},
issn = {2079-9721},
abstract = {Introduction: As life expectancy increases, the prevalence of frailty and eye diseases (cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy) in the elderly global population is rising. Eye diseases and visual impairment not only contribute to a high incidence of falls, fractures, depression, and social isolation but they also herald cognitive decline and frailty (vision-cognitive impairment). Methods: This narrative review explores the relationship between eye diseases, visual impairment, and frailty, their association with cognitive decline, the current approaches in identifying and managing these conditions and the potential role of interdisciplinary care models. Relevant articles were identified by searching the major databases. Result: Eye diseases are common in elderly individuals and can lead to visual impairment and subsequently contribute to falls, fractures, depression, and social isolation. Visual impairment is strongly linked to cognitive decline, which is a key component of frailty. Reduced sensory input from vision loss leads to decreased cognitive stimulation, reduced engagement in activities such as reading, problem-solving, executive function, attention, and social interactions, which are crucial for maintaining cognitive health. This can lead to a form of "sensory deprivation", which accelerates neurodegenerative processes. As cognitive decline progresses, it creates a feedback loop where individuals may struggle to manage their health, adhere to treatment regimens, or seek timely medical care, exacerbating both cognitive impairment and frailty. Additionally, subjective cognitive decline (SCD) is common in older adults with vision loss and may precede clinical dementia. This sense of declining cognitive ability can worsen anxiety and depression, further contributing to frailty. Early intervention has the potential to mitigate the cognitive effects of vision loss (vision-cognitive impairment). Conclusions: Ophthalmologists should play an important role in detecting frailty associated with vision loss. Incorporating frailty assessments into ophthalmic practice can facilitate referrals to geriatric care and early interventions, improving patient outcomes. Geriatricians should be vigilant in identifying visual impairment and referring patients for appropriate ophthalmic investigation and management. Regular vision assessments should be part of comprehensive geriatric evaluations. Future research will assess the beneficial role of community geriatricians in detecting frailty and vision-cognitive impairment. An interdisciplinary and collaborative approach between ophthalmologists and geriatricians can lead to earlier detection, comprehensive management, and improved outcomes in frailty, eye diseases, and cognitive function.},
}
@article {pmid39589346,
year = {2024},
author = {Hernandez, BJ and Strain, M and Suarez, MF and Stamer, WD and Ashley-Koch, A and Liu, Y and Klingeborn, M and Bowes Rickman, C},
title = {Small Extracellular Vesicle-Associated MiRNAs in Polarized Retinal Pigmented Epithelium.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {13},
pages = {57},
pmid = {39589346},
issn = {1552-5783},
support = {P20 GM152335/GM/NIGMS NIH HHS/United States ; R21 EY033057/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; R01 EY032960/EY/NEI NIH HHS/United States ; F31 EY033170/EY/NEI NIH HHS/United States ; P30 EY031631/EY/NEI NIH HHS/United States ; R21 EY033961/EY/NEI NIH HHS/United States ; R21 EY028671/EY/NEI NIH HHS/United States ; P30 EY005722/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism ; Animals ; *MicroRNAs/genetics/metabolism ; Swine ; *Extracellular Vesicles/metabolism/genetics ; *Oxidative Stress ; Cells, Cultured ; Real-Time Polymerase Chain Reaction ; Cell Polarity/physiology ; },
abstract = {PURPOSE: Oxidative stress in the retinal pigmented epithelium (RPE) has been implicated in age-related macular degeneration by impacting endocytic trafficking, including the formation, content, and secretion of extracellular vesicles (EVs). Using our model of polarized primary porcine RPE (pRPE) cells under chronic subtoxic oxidative stress, we tested the hypothesis that RPE miRNAs packaged into EVs are secreted in a polarized manner and contribute to maintaining RPE homeostasis.<br><br>METHODS: Small EVs (sEVs) enriched for exosomes were isolated from apical and basal conditioned media from pRPE cells grown for up to four weeks with or without low concentrations of hydrogen peroxide using two sEV isolation methods, leading to eight experimental groups. The sEV miRNA expression was profiled using miRNA-Seq with Illumina MiSeq, followed by quality control and bioinformatics analysis for differential expression using the R computing environment. Expression of selected miRNAs were validated using qRT-PCR.<br><br>RESULTS: We identified miRNA content differences carried by sEVs isolated using two ultracentrifugation-based methods. Regardless of the sEV isolation method, miR-182 and miR-183 were enriched in the cargo of apically secreted sEVs, and miR-122 in the cargo of basally secreted sEVs from RPE cells during normal homeostatic conditions. After oxidative stress, miR-183 levels were significantly decreased in the cargo of apically released sEVs from stressed RPE cells.<br><br>CONCLUSIONS: We curated RPE sEV miRNA datasets based on cell polarity and oxidative stress. Unbiased miRNA analysis identified differences based on polarity, stress, and sEV isolation methods. These findings suggest that miRNAs in sEVs may contribute to RPE homeostasis and function in a polarized manner.},
}
@article {pmid39588880,
year = {2025},
author = {Dong, XX and Hu, HH and Ying, ZQ and Chen, DL and Xie, JY and Li, DL and Hu, DN and Lanca, C and Grzybowski, A and Pan, CW},
title = {Major sight-threatening eye disorders and mental disorders.},
journal = {Acta ophthalmologica},
volume = {103},
number = {3},
pages = {257-271},
doi = {10.1111/aos.16800},
pmid = {39588880},
issn = {1755-3768},
support = {82122059//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Comorbidity ; *Eye Diseases/epidemiology ; Global Health ; *Mental Disorders/epidemiology ; Prevalence ; },
abstract = {The purpose of this study was to: (a) investigate the comorbidities of major sight-threatening eye disorders with mental disorders, (b) investigate the associations and prevalence of reported comorbidities and (c) identify potential influencing factors. A systematic review of the PubMed, Embase, Web of Science and Cochrane Library databases was conducted from inception to 30 December 2023. Studies that presented only laboratory results or used non-representative sampling methods were excluded. Meta-analyses were performed using the inverse variance method with a random-effects model. A total of 67 studies were included in the analysis. The most prevalent comorbidities were diabetic retinopathy (DR) and depression (pooled prevalence of 30%) and DR and anxiety (pooled prevalence of 29%). Significant associations were found between glaucoma and depression (odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.21-1.66), glaucoma and anxiety (OR = 2.11, 95% CI = 1.22-3.66), glaucoma and schizophrenia (OR = 1.38, 95% CI = 1.28-1.50), age-related macular degeneration (AMD) and depression (OR = 1.36, 95% CI = 1.18-1.57), and DR and depression (OR = 1.03, 95% CI = 1.01-1.06). Income was identified as a significant contributing factor to the prevalence of comorbidity between glaucoma and depression. Major sight-threatening eye disorders were significantly associated with mental disorders, particularly depression and anxiety. The burden of comorbidity between major sight-threatening eye disorders and mental disorders is not optimistic and may be influenced by income disparities. Healthcare providers are encouraged to assess and manage potential comorbidities to optimize patient outcomes.},
}
@article {pmid39588040,
year = {2024},
author = {Liu, Z and Wang, Q and Li, L and Cai, S},
title = {Association between dietary consumption of multiple vitamins and age-related macular degeneration: a cross-sectional observational study in the National Health and Nutrition Examination Survey 2005-2008.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1504081},
pmid = {39588040},
issn = {2296-861X},
abstract = {PURPOSE: Age-related macular degeneration (AMD) is one of the common causes of blindness in the elderly worldwide. Its prevention and monitoring indicators remain a key area of research. This study aims to examine the association between vitamin intake and AMD prevalence.<br><br>METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008 were used for cross-sectional analysis. Logistic regression models, subgroup analyses and multicollinearity regression were employed to assess the association between vitamin intake and AMD.<br><br>RESULTS: A total of 1,627 participants were included, with 54.5% (weighted) males and 45.5% (weighted) females. Significant differences were observed in the intake of vitamins B (B1, B2, B6, and B12), E, and folic acid between the AMD and Non-AMD groups. The Non-AMD group had higher average intakes (weighted) of vitamin B1 (1.71&#x2009;&#xb1;&#x2009;1.10 vs. 1.37&#x2009;&#xb1;&#x2009;0.64), B2 (2.42&#x2009;&#xb1;&#x2009;1.22 vs. 1.86&#x2009;&#xb1;&#x2009;0.70), B6 (2.05&#x2009;&#xb1;&#x2009;1.25 vs. 1.71&#x2009;&#xb1;&#x2009;0.85), B12 (5.73&#x2009;&#xb1;&#x2009;6.18 vs. 4.54&#x2009;&#xb1;&#x2009;3.27), E (7.93&#x2009;&#xb1;&#x2009;5.47 vs. 6.39&#x2009;&#xb1;&#x2009;2.86), and folic acid (181.87&#x2009;&#xb1;&#x2009;178.04 vs. 140.72&#x2009;&#xb1;&#x2009;124.60). Logistic regression and subgroup analyses further supported these findings.<br><br>CONCLUSION: This study found that higher vitamin intakes B and E were associated with a lower prevalence of AMD in the U.S. population. Eating a healthy diet rich in vitamins B and E, particularly B2 (eggs, green vegetables, meat, mushrooms, and almonds) may help to reduce vision loss due to AMD. However, since this is a cross-sectional study, causal associations between vitamin intake and AMD cannot be established. Further randomized clinical trials are needed to confirm these findings.},
}
@article {pmid39587629,
year = {2024},
author = {Gong, Y and Huang, X and Tu, T and Chu, C and Xian, C and Yuan, Y and Fu, X and Li, R and Zhong, G and Zhou, X},
title = {A novel AAV Vector for gene therapy of RPE-related retinal degenerative diseases via intravitreal delivery.},
journal = {Molecular neurodegeneration},
volume = {19},
number = {1},
pages = {89},
pmid = {39587629},
issn = {1750-1326},
support = {2022YFF1202901//Key Research and Development Program of the Ministry of Science and Technology/ ; 82171404//National Natural Science Foundation of China/ ; 2023A1515011529//Natural Science Foundation of Guangdong Province/ ; 2023A03J0181, 2024A04J6481//Science and Technology Planning Project of Guangzhou City/ ; 22yklj04//the Fundamental Research Funds for the Central Universities/ ; Funded Talent[2020]18//the Research Start-up Founds of Sun Yat-sen University/ ; },
}
@article {pmid39587331,
year = {2025},
author = {Vidal-Oliver, L and Fernández-Avellaneda, P and Fragiotta, S and Corradetti, G and Borrelli, E and Dolz-Marco, R},
title = {Non-exudative OCT findings in neovascular AMD.},
journal = {Eye (London, England)},
volume = {39},
number = {3},
pages = {516-526},
pmid = {39587331},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/diagnostic imaging ; *Retinal Pigment Epithelium/pathology ; *Choroidal Neovascularization ; },
abstract = {In this narrative review we describe the main optical coherence tomography biomarkers appearing in eyes with neovascular age-related macular degeneration (AMD) that do not directly correspond to exudation. We highlight those signs that may mimic exudation and therefore do not require active treatment, such as outer retinal tubulations, pseudocysts, lipid globules, or hyporeflective wedges. Other signs may indicate impending exudation such as hyperreflective foci or shallow irregular retinal pigment epithelium elevation, and therefore should be carefully monitored. We also review and summarize the different origins of subretinal hyperreflective material and describe the main signs of degeneration seen in eyes with AMD, such as outer retinal tubulation, thinning of the retinal layers, outer retinal atrophy, and choroidal changes.},
}
@article {pmid39586847,
year = {2025},
author = {Krieger, J and Cox, O and Flacke, JP and Beilschmidt, L and Mueller, S and Maywald, U and Koss, MJ},
title = {Real-world therapy and persistence of patients with neovascular age-related macular degeneration and diabetic retinopathy or diabetic macular edema: a German claims data analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {3},
pages = {713-725},
pmid = {39586847},
issn = {1435-702X},
mesh = {Humans ; Female ; Male ; *Diabetic Retinopathy/drug therapy/complications/diagnosis/epidemiology ; *Macular Edema/drug therapy/etiology/diagnosis/epidemiology ; Angiogenesis Inhibitors/administration &amp; dosage ; Germany/epidemiology ; Intravitreal Injections ; Aged, 80 and over ; Aged ; *Wet Macular Degeneration/drug therapy/epidemiology/diagnosis/complications ; *Bevacizumab/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; Follow-Up Studies ; *Visual Acuity ; *Ranibizumab/administration &amp; dosage ; Middle Aged ; Databases, Factual ; },
abstract = {PURPOSE: Vascular endothelial growth factor (VEGF) inhibition is the current and high-volume standard-of-care for patients with neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR) with diabetic macular edema (DME). This study assessed the impact of non-persistence in anti-VEGF treatment using claims data from two German states.<br><br>METHODS: This study identified adults with nAMD or DR/DME and incident anti-VEGF treatment (=&#x2009;index) in January 2015-June 2019 using the German AOK PLUS claims database (January 2014-June 2021,&#x2009;~&#x2009;3.5 million insured). Baseline characteristics were observed within 12&#xa0;months before index. Patient follow-up lasted&#x2009;&#x2265;&#x2009;24&#xa0;months or until death. Non-persistence (gap of&#x2009;&#x2265;&#x2009;180&#xa0;days) was calculated using Kaplan-Meier estimation. Cox regression identified variables linked to non- persistence. The study analysed reimbursed anti-VEGF treatments, thus excluding off-label use of bevacizumab.<br><br>RESULTS: 5,498 patients diagnosed with nAMD (mean age, 80.09&#xa0;years; male, 37.50%; mean Charlson Comorbidity Index [CCI] score, 3.07) and 484 patients with DR/DME (mean age, 67.14; male, 58.88%; mean CCI score, 4.54) were identified. Non-persistence to anti-VEGF treatment within 12&#xa0;months after index occurred in 51.38% of nAMD patients and 62.60% of DR/DME patients, with mean times to first gap of 11.28 and 8.98&#xa0;months, respectively. Cox regression revealed factors associated with non-persistence, including higher age, female gender, higher care needs, longer AMD history, and the use of ranibizumab.<br><br>CONCLUSION: Epidemiologic and ophthalmologic factors associated with anti-VEGF non-persistence were successfully identified in the first year of therapy. The analyzed dataset can potentially be enriched with additional health insurance database sets under the used criteria to gain more understanding of anti-VEGF non-persistence.},
}
@article {pmid39586714,
year = {2025},
author = {Guo, S and Liu, X and Cheng, X and Jiang, Y and Ji, S and Liang, Q and Koval, A and Li, Y and Owen, LA and Kim, IK and Aparicio, A and Lee, S and Sood, AK and Kopetz, S and Shen, JP and Weinstein, JN and DeAngelis, MM and Chen, R and Wang, W},
title = {A deconvolution framework that uses single-cell sequencing plus a small benchmark data set for accurate analysis of cell type ratios in complex tissue samples.},
journal = {Genome research},
volume = {35},
number = {1},
pages = {147-161},
pmid = {39586714},
issn = {1549-5469},
support = {S10 OD018033/OD/NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA268380/CA/NCI NIH HHS/United States ; S10 OD023469/OD/NIH HHS/United States ; P30 EY002520/EY/NEI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; S10 OD025240/OD/NIH HHS/United States ; R01 CA239342/CA/NCI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; R01 EY022356/EY/NEI NIH HHS/United States ; K22 CA234406/CA/NCI NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 EY018571/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Single-Cell Analysis/methods ; Female ; *Ovarian Neoplasms/genetics/pathology/drug therapy ; Benchmarking ; Macular Degeneration/genetics/pathology ; Sequence Analysis, RNA/methods ; Retina/metabolism ; RNA-Seq/methods ; },
abstract = {Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we utilize an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using this well-matched, that is, benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using two benchmark data sets of healthy retinas and ovarian cancer tissues suggest much-improved deconvolution accuracy. Leveraging tissue-specific benchmark data sets, we applied DeMixSC to a large cohort of 453 age-related macular degeneration patients and a cohort of 30 ovarian cancer patients with various responses to neoadjuvant chemotherapy. Only DeMixSC successfully unveiled biologically meaningful differences across patient groups, demonstrating its broad applicability in diverse real-world clinical scenarios. Our findings reveal the impact of technological discrepancy on deconvolution performance and underscore the importance of a well-matched data set to resolve this challenge. The developed DeMixSC framework is generally applicable for accurately deconvolving large cohorts of disease tissues, including cancers, when a well-matched benchmark data set is available.},
}
@article {pmid39585864,
year = {2024},
author = {Pfister, IB and Schild, C and Garweg, JG},
title = {Predicting long-term functional anti-VEGF treatment outcomes in neovascular AMD in a real-world setting.},
journal = {PloS one},
volume = {19},
number = {11},
pages = {e0314167},
pmid = {39585864},
issn = {1932-6203},
mesh = {Humans ; Male ; Female ; Aged ; Retrospective Studies ; *Visual Acuity ; Treatment Outcome ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Wet Macular Degeneration/drug therapy/physiopathology ; Middle Aged ; Tomography, Optical Coherence ; Ranibizumab/therapeutic use/administration &amp; dosage ; },
abstract = {PURPOSE: To test to what degree retinal fluid (RF) after the loading phase and at the end of year 1 predicts long-term functional outcomes in neovascular macular degeneration (nAMD), as do macular (MA) atrophy, treatment density and treatment interval extension.<br><br>METHODS: In this retrospective single-center cohort study, a consecutive series of eyes with treatment-na&#xef;ve nAMD followed under a treat-and-extend (T&amp;E) protocol followed over &#x2265;2 years. Best-corrected visual acuity (BCVA), presence of retinal fluid (RF) and macular atrophy (MA) were registered along with central retinal thickness (CRT) and treatment density over time. The relationship between these variables was tested by regression analysis.<br><br>RESULTS: A total of 433 eyes were followed for 4.9 &#xb1; 2.2 years. A series of univariate analyses were run to select the covariates for the final multivariate regression model. CRT after loading, time to dryness, intraretinal fluid and MA after one year were found to predict visual function over 2 to 5 years. A final regression model was adjusted for visual acuity (VA) at baseline and showed that CRT after loading was predictive only in the short term (2 years) and that MA had the greatest predictive value for VA after 2 to 5 years. Intraretinal fluid (IRF) significantly predicted VA only after 4 years. The final regression model explained 21 to 32% of the variation in VA.<br><br>CONCLUSIONS: In this large retrospective cohort, the presence of MA after one year was the strongest predictor of VA after 2 to 5 years, explaining a vision loss of 13 to 20 letters. The presence of IRF and SRF at any point of time had a comparably weak predictive potential for the outcomes over 5 and more years.},
}
@article {pmid39585675,
year = {2024},
author = {Jaskoll, S and Kramer, A and Elbaz-Hayoun, S and Rinsky, B and Eandi, CM and Grunin, M and Shwartz, Y and Tiosano, L and Heid, IM and Winkler, T and Chowers, I},
title = {Adult Onset Foveomacular Vitelliform Dystrophy Shows Genetic Overlap With Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {13},
pages = {53},
pmid = {39585675},
issn = {1552-5783},
support = {R01 EY022310/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; *Polymorphism, Single Nucleotide ; Aged ; *Vitelliform Macular Dystrophy/genetics ; *Macular Degeneration/genetics ; Middle Aged ; Genotype ; Complement Factor H/genetics ; Tomography, Optical Coherence ; Aged, 80 and over ; Phenotype ; Genetic Predisposition to Disease ; },
abstract = {PURPOSE: Adult-onset foveomacular vitelliform dystrophy (AFVD) shares phenotypic similarities with age-related macular degeneration (AMD). The genetic factors associated with AFVD are unknown in >80% of cases. This study evaluated the association of known AMD genetic risk variants with AFVD and compared systemic complement activation in these conditions.<br><br>METHODS: Clinical, imaging, and genetic data were collected from 50 patients with AFVD (men/women = 25/25, mean age &#xb1; SD 73 &#xb1; 10 years), 917 patients with AMD (men/women = 377/540, mean age &#xb1; SD 77 &#xb1; 9 years), and 432 unaffected healthy controls (men/women = 202/230, mean age &#xb1; SD 71 &#xb1; 8 years). Genotyping focused on 52 single nucleotide polymorphisms (SNPs) linked to AMD. Weighted genetic risk scores (GRS) for 19 complement system associated variants, 7 lipid metabolism associated variants, the remaining 26 variants (other pathways GRS), and for all 52 variants (global score) were derived and correlated with phenotype.<br><br>RESULTS: Of the 52 SNPs evaluated, CFH (rs570618) and C2/CFB/SKIV2L (rs116503776 and rs114254831) were associated with AFVD compared with healthy controls (odds ratio [OR] = 2.73, 95% confidence interval [CI] = 1.32-5.73, P = 0.01; OR = 0.31, 95% CI = 0.14-0.71, P = 0.0036; and OR = 0.41, 95% CI = 0.22-0.74, P = 0.0025, respectively). MIR6130/RORB (rs10781182) was negatively associated with AFVD compared with the healthy controls (OR = 0.13, CI = 0.06-0.25, P < 0.0001) and AMD (OR = 0.19, CI = 0.10-0.34, P < 0.0001). Regression analysis showed complement GRS was positively associated with AFVD compared with controls (OR = 1.42, 95% CI = 1.04-1.95, P = 0.03), whereas the other pathways' GRS was negatively associated (OR = 0.46, 95% CI = 0.21-0.98, P = 0.04). AMD was positively associated with the complement score, global score, and ARMS2/HTRA1 compared with controls.<br><br>CONCLUSIONS: Non-monogenic AFVD is associated with AMD risk alleles in the complement cascade, but not in other pathways. Further research is needed to explore complement inhibition for AFVD.},
}
@article {pmid39584280,
year = {2025},
author = {Andreadi, A and Hallam, TM and Brocklebank, V and Sharp, SJ and Walsh, PR and Southerington, T and Hautalahti, M and Steel, DH and Lotery, AJ and Harris, CL and Marchbank, KJ and Kavanagh, D and Jones, AV},
title = {The role of complement factor I rare genetic variants in age related macular degeneration in Finland.},
journal = {Human molecular genetics},
volume = {34},
number = {3},
pages = {218-228},
pmid = {39584280},
issn = {1460-2083},
support = {MR/R000913/1//Medical Research Council/Kidney Research UK Clinical Research Training Fellow/ ; R01-EY028602//US National Institutes of Health/ ; MR/X020975/1/MRC_/Medical Research Council/United Kingdom ; R01 EY028602/EY/NEI NIH HHS/United States ; R01 EY011309/EY/NEI NIH HHS/United States ; //NIHR Newcastle Biomedical Research Centre at Newcastle upon Tyne Hospitals NHS Foundation Trust/ ; /WT_/Wellcome Trust/United Kingdom ; RES/0248/7836//Wellcome Trust: 4Ward North Academy/ ; },
mesh = {Humans ; Finland ; *Macular Degeneration/genetics/pathology ; *Complement Factor I/genetics/metabolism ; Female ; Genetic Predisposition to Disease ; Male ; Aged ; Gene Frequency ; Polymorphism, Single Nucleotide ; Genetic Variation ; Genotype ; Middle Aged ; Complement Pathway, Alternative/genetics ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. The alternative pathway (AP) of complement has been linked to the pathogenesis of AMD. In particular, rare variants (RVs) in the complement factor I (CFI) gene encoding the Factor I (FI) protein confer increased AMD risk. The prevalence of CFI RVs are well characterised in European AMD, however little is known about other populations. The Finnish population underwent genetic restriction events which have skewed allele frequencies in unexpected ways. A series of novel or enriched CFI RVs were identified in individuals with dry AMD from the Finnish Biobank Cooperative (FINBB), but the relationship between these genotypes and contribution to disease was unclear. Understanding how RVs impact the ability of FI to regulate the complement system is important to inform mechanistic understanding for how different genotypes contribute to disease development. To explore this a series of in vitro assays were used to functionally characterise the protein products of 3 CFI RVs enriched in FINBB dry AMD, where no prior data were available. The G547R variant resulted in almost complete loss of both classical pathway and AP regulatory potential. The c.982 g>a variant encoding G328R FI perturbed an exon splice enhancer site which resulted in exon skipping and a premature stop codon in vitro and low levels of FI in vivo. Despite detailed analysis no defect in levels or function was demonstrated in T107A. Functional characterization of all Finnish CFI RVs in the cohort allowed us to demonstrate that in Finnish dry AMD, collectively the type 1 CFI RVs (associated with FI haploinsufficiency) were significantly enriched with odds ratio (ORs) of 72.6 (95% confidence interval; CI 16.92 to 382.1). Meanwhile, type 2 CFI RVs (associated with FI dysfunction) collectively conferred a significant OR of 4.97 (95% CI 1.522 to 15.74), and non-impaired or normal CFI RV collectively conferred an of OR 3.19 (95% CI 2.410 to 4.191) although this was driven primarily by G261D. Overall, this study for the first time determined the ORs and functional effect for all CFI RVs within a Geographic Atrophy (GA) cohort, enabling calculations of combined risk scores that underline the risk conferred by type 1 and 2 CFI RVs in GA/AMD.},
}
@article {pmid39584184,
year = {2025},
author = {Dhodapkar, RM and Jung, E and Lee, SY},
title = {An Eye on Extracellular Vesicles: Trends and Clinical Translations in Vision Research.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100619},
pmid = {39584184},
issn = {2666-9145},
support = {R01 EY034193/EY/NEI NIH HHS/United States ; R21 EY035425/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To perform a review of research, funding, and clinical translation efforts for extracellular vesicles (EVs) within vision science.<br><br>DESIGN: Retrospective analysis of publication, funding, and clinical trials data.<br><br>METHODS: A pretrained large language model (Jina2) was used to create semantic embeddings for 41&#xa0;282 abstracts from articles related to EVs archived on EMBASE and published between January 1966 and January 2024. The articles were projected and clustered according to semantic embedding similarity, and research subdomains for EVs were determined through inspection of term frequency-inverse document frequency weighted word clouds. Mann-Kendall trend analysis was performed to identify current areas of growth within EV research. Additionally, National Institutes of Health funding data from RePORT Expenditures and Results and clinical trials data from ClinicalTrials.gov were analyzed to correlate publication trends with funding support and clinical translation efforts.<br><br>RESULTS: Unsupervised clustering and Mann-Kendall trend analysis identified wound healing/regeneration (P&#xa0;=&#xa0;0.030) and neurodegenerative disease (P&#xa0;=&#xa0;0.049) as significantly accelerating in growth of publication over time. Ophthalmology-restricted subset analysis identified that publications in age-related macular degeneration (P&#xa0;=&#xa0;0.191) and clinical applications (P&#xa0;=&#xa0;0.086) are no longer growing at a significant rate. Analysis of funding data identified that the National Cancer Institute was the top funding institution overall, but that the National Institute on Aging is rapidly advancing in terms of funding EV research and trials. Analysis of ClinicalTrials.gov data highlights a dearth of clinical trials within ophthalmology despite a growing number of studies in other medical subfields.<br><br>CONCLUSIONS: Extracellular vesicles remain a promising substrate for both the identification and treatment of vision-threatening diseases. A better understanding of the current landscape of research and funding trends should help to inform future funding and translational efforts.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39584182,
year = {2025},
author = {Heckenlaible, NJ and Toomey, CB and Handa, JT},
title = {OCT Changes Observed during the Progression of Early Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100615},
pmid = {39584182},
issn = {2666-9145},
support = {K08 EY035322/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Automated retinal cell layer segmentation empowers OCT as a precise tool for characterizing morphologic features of retinal health throughout age-related macular degeneration (AMD) progression, particularly in advance of more visible biomarkers such as drusen and macular pigmentary changes. Few studies have examined OCT changes in eyes progressing from early to intermediate disease, or combined examinations of cell layer thickness, reflectivity, and heterogeneity. Therefore, this study analyzed OCTs from eyes progressing from early to intermediate AMD to identify changes in retinal morphology and reflectivity that may serve as biomarkers of early progression.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients &#x2265;50 years with a diagnosis of AMD and with high-quality ipsilateral OCTs in both early and intermediate stage disease.<br><br>METHODS: Fifty OCTs from 25 patients were automatically segmented using a previously validated artificial intelligence-driven algorithm. Changes in the mean and standard deviation of cell layer thickness and reflectivity with progression through stages were calculated for 90 retinal volumes with the help of a novel Python-based analysis tool.<br><br>MAIN OUTCOME MEASURES: The primary outcomes were significant changes to cell layer thickness, reflectivity, and heterogeneity with progression of AMD.<br><br>RESULTS: With progression from early to intermediate disease, photoreceptor outer segments diffusely thinned. Within the ellipsoid zone, the fovea and parafovea were thinned with a simultaneous increase in thickness variability and a decrease in parafoveal reflectivity. The retinal pigment epithelium-Bruch's membrane complex underwent diffuse thickening and increased thickness variability alongside a decrease in foveal and parafoveal reflectivity.<br><br>CONCLUSIONS: These findings correlate with the known histopathology of early AMD and identify measurable OCT trends through the earliest stages of disease.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39581910,
year = {2025},
author = {Long, H and Xiong, Y and Liu, H and Yang, M and Liu, T and Gong, C and Li, S},
title = {IL-6 Exacerbates Oxidative Damage of RPE Cells by Indirectly Destabilizing the mRNA of DNA Repair Genes.},
journal = {Inflammation},
volume = {48},
number = {4},
pages = {2323-2340},
pmid = {39581910},
issn = {1573-2576},
support = {202210313031Z//Jiangsu Training Program of Innovation and Entrepreneurship for Undergraduates/ ; 82103334//National Natural Science Foundation of China/ ; KC23071//Basic Research Plan of Xuzhou Science and Technology Project/ ; BK20211052//Natural Science Foundation of Jiangsu Province/ ; },
mesh = {*Oxidative Stress/physiology/drug effects ; Humans ; *DNA Repair/genetics ; *RNA, Messenger/metabolism/genetics ; Animals ; *Interleukin-6/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Serine-Arginine Splicing Factors/metabolism/genetics ; Mice ; *RNA Stability ; Apoptosis ; DNA Damage ; Macular Degeneration/metabolism/pathology/genetics ; E2F1 Transcription Factor/metabolism ; Diabetic Retinopathy/metabolism/pathology/genetics ; },
abstract = {Chronic inflammation has been associated with the progression of age-related macular degeneration (AMD) and diabetic retinopathy (DR), and the levels of various inflammatory factors are significantly increased in intraocular fluids of patients with AMD and DR. Therefore, elucidating the roles of inflammatory factors in the oxidative damage of RPE cells will help uncover the pathogenesis of AMD and DR. We have previously demonstrated that E2F1 plays an important role in the antioxidant capacity of RPE cells. Here, our transcriptome analysis shows that E2F1 affected the expressions of DNA repair genes in RPE cells. In addition, we found that E2F1 transactivated the splicing factor SRSF1. SRSF1 knockdown promoted DNA oxidative damage and apoptosis and decreased the mRNA stability of DNA repair genes XRCC2, POLK and LIG4 in RPE cells. Moreover, we found that SRSF1 could bind to the RNA stabilizing factor MATR3, and knockdown of the latter affected the mRNA stability of these DNA repair genes. Notably, interleukin-6 (IL-6), an inflammatory factor upregulated in intraocular fluids of patients with AMD and DR, decreased SRSF1 expression by inducing acetylation of E2F1 at the K125 position. Consistently, SRSF1 overexpression relieved IL-6-induced DNA oxidative damage and apoptosis in RPE cells. In vivo experiment results also confirmed that IL-6 could aggravate retinal oxidative damage. In conclusion, high levels of IL-6 in the eyes of patients with AMD and DR destabilize the mRNAs of DNA repair genes by disrupting the expression of SRSF1, leading to abnormal repair of DNA oxidative damage in RPE cells.},
}
@article {pmid39581330,
year = {2025},
author = {Anegondi, N and Steffen, V and Sadda, SR and Schmitz-Valckenberg, S and Tufail, A and Csaky, K and Lad, EM and Kaiser, PK and Ferrara, D and Chakravarthy, U},
title = {Visual Loss in Geographic Atrophy: Learnings from the Lampalizumab Trials.},
journal = {Ophthalmology},
volume = {132},
number = {4},
pages = {420-430},
doi = {10.1016/j.ophtha.2024.11.017},
pmid = {39581330},
issn = {1549-4713},
mesh = {Humans ; *Geographic Atrophy/physiopathology/drug therapy/diagnosis/etiology ; *Visual Acuity/physiology ; Retrospective Studies ; Male ; Female ; Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Fluorescein Angiography ; Intravitreal Injections ; Prospective Studies ; Tomography, Optical Coherence ; Aged, 80 and over ; Fovea Centralis/pathology ; Follow-Up Studies ; Middle Aged ; Immunoglobulin Fab Fragments ; },
abstract = {PURPOSE: To assess the correlation of lesion growth rate and baseline factors, including foveal involvement and focality, on visual loss as measured by best-corrected visual acuity (BCVA) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective analysis of the lampalizumab phase 3 (NCT02247479 and NCT02247531) and prospective observational (NCT02479386) trials.<br><br>PARTICIPANTS: Patients with bilateral GA.<br><br>METHODS: Monthly BCVA and fundus autofluorescence (FAF) at baseline and every 6 months for 2 years were analyzed. Baseline GA area from FAF images was correlated to baseline BCVA and change in BCVA. The lesion growth rate was calculated as the slope of a linear fit from all available GA area measurements of a patient. The association between GA growth rate quartiles and BCVA changes was assessed, subgrouped by GA foveal involvement or focality. Time-to-event analysis for BCVA loss of &#x2265;5, &#x2265;10, and &#x2265;15 letters was performed. A Cox regression model adjusted for baseline factors was performed on these outcomes. Kaplan-Meier curves are provided for each baseline factor and GA growth rate.<br><br>MAIN OUTCOME MEASURES: Correlations of baseline BCVA, GA area, and growth rate with change in BCVA, and time to &#x2265;5, &#x2265;10, and &#x2265;15-letter loss by foveal involvement or focality.<br><br>RESULTS: Best-corrected visual acuity and GA area at baseline did not correlate with BCVA change at any visit. Geographic atrophy growth rate showed a weak correlation with BCVA loss, which increased over time. The 2 highest GA growth rate quartiles had accelerated BCVA loss in eyes with subfoveal, unifocal lesions. Approximately 75%, 50%, and 25% of study eyes experienced a &#x2265;5-, &#x2265;10-, and &#x2265;15-letter loss by 2 years, respectively.<br><br>CONCLUSIONS: Best-corrected visual acuity and GA area at baseline did not correlate with BCVA loss, but faster GA growth rates appeared to be associated with faster BCVA loss. Geographic atrophy foveal involvement and focality correlated with the rate of BCVA loss with subfoveal lesions at high risk of vision loss over time, especially when the GA lesion was unifocal.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39581257,
year = {2025},
author = {Yu Rice, Y and Dolan, DG and Bandara, SB and Morgan, RE and Garry, M and Tsuji, J},
title = {Considerations and derivations of permitted daily exposure limits for impurities from intravitreal pharmaceutical products.},
journal = {Regulatory toxicology and pharmacology : RTP},
volume = {155},
number = {},
pages = {105745},
doi = {10.1016/j.yrtph.2024.105745},
pmid = {39581257},
issn = {1096-0295},
mesh = {*Intravitreal Injections ; *Drug Contamination ; Humans ; *Vitreous Body ; Pharmaceutical Preparations/chemistry/analysis ; Animals ; },
abstract = {Intravitreal (IVT) injection is an uncommon route of parenteral administration for therapeutic medications, but one of the most important for the treatment of ocular diseases, especially those related to macular degeneration. Nonetheless, there are currently no regulatory guidelines that specifically address how to establish a permitted daily exposure (PDE) for impurities and residual process reagents in IVT pharmaceutical drug products given the unique vulnerability of ocular tissues. The establishment of PDEs for IVT administration is complicated by the limited understanding of metabolism and clearance of small molecular weight chemicals from the human vitreous humor (VH), a problem compounded by the limited IVT-specific toxicological data. In this paper, we describe a feasible and comprehensive methodology for deriving PDE limits for impurities and residual process reagents from IVT drug products, as exemplified by five case studies, including inorganic elements, formic acid, polyethylene glycols, acetic acid, and caprolactam. The five case studies were selected to cover compounds with a wide range of impurity sources and toxicological data availability. The proposed framework considers both local ocular and systemic toxicity endpoints and advances the goal of a harmonized, science-based approach for deriving IVT PDE limits.},
}
@article {pmid39580658,
year = {2025},
author = {Lunegova, DA and Gvozdev, DA and Senin, II and Gudkova, VR and Sidorenko, SV and Tiulina, VV and Shebardina, NG and Yakovleva, MA and Feldman, TB and Ramonova, AA and Moysenovich, AM and Semenov, AN and Zernii, EY and Maksimov, EG and Sluchanko, NN and Kirpichnikov, MP and Ostrovsky, MA},
title = {Antioxidant properties of the soluble carotenoprotein AstaP and its feasibility for retinal protection against oxidative stress.},
journal = {The FEBS journal},
volume = {292},
number = {2},
pages = {355-372},
doi = {10.1111/febs.17335},
pmid = {39580658},
issn = {1742-4658},
support = {23-SH04-09//Interdisciplinary Scientific and Educational School of Lomonosov Moscow State University 'Molecular Technologies of the Living Systems and Synthetic Biology'/ ; 24-15-00171//Russian Science Foundation/ ; //Program of the Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {*Oxidative Stress/drug effects ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Zeaxanthins/pharmacology ; *Antioxidants/pharmacology/chemistry ; Humans ; Reactive Oxygen Species/metabolism ; Carotenoids ; Animals ; *Algal Proteins/pharmacology/chemistry/genetics ; Lipofuscin/metabolism ; Macular Degeneration/metabolism/pathology ; Recombinant Proteins/pharmacology/chemistry ; },
abstract = {Photodamage to the outer segments of photoreceptor cells and their impaired utilization by retinal pigment epithelium (RPE) cells contribute to the development of age-related macular degeneration (AMD) leading to blindness. Degeneration of photoreceptor cells and RPE cells is triggered by reactive oxygen species (ROS) produced by photochemical reactions involving bisretinoids, by-products of the visual cycle, which accumulate in photoreceptor discs and lipofuscin granules of RPE. Carotenoids, natural antioxidants with high potential efficacy against a wide range of ROS, may protect against the cytotoxic properties of lipofuscin. To solve the problem of high hydrophobicity of carotenoids and increase their bioaccessibility, specialized proteins can ensure their targeted delivery to the affected tissues. In this study, we present new capabilities of the recombinant water-soluble protein AstaP from Coelastrella astaxanthina Ki-4 (Scenedesmaceae) for protein-mediated carotenoid delivery and demonstrate how zeaxanthin delivery suppresses oxidative stress in a lipofuscin-enriched model of photoreceptor and pigment epithelium cells. AstaP in complex with zeaxanthin can effectively scavenge various ROS (singlet oxygen, free radical cations, hydrogen peroxide) previously reported to be generated in AMD. In addition, we explore the potential of optimizing the structure of AstaP to enhance its thermal stability and resistance to proteolytic activity in the ocular media. This optimization aims to maximize the prevention of retinal degenerative changes in AMD.},
}
@article {pmid39579005,
year = {2025},
author = {Wagner, M and Sommerer, J and Rauscher, FG},
title = {Extracting full information from OCT scans-signs of early age-related macular degeneration within inner retinal layers by local neighbourhood statistics. Part II: Results.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {1},
pages = {247-268},
pmid = {39579005},
issn = {1475-1313},
support = {497989466//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; *Macular Degeneration/epidemiology/diagnosis ; Aged ; Case-Control Studies ; *Retina/diagnostic imaging/pathology ; Middle Aged ; },
abstract = {BACKGROUND AND OBJECTIVES: Associations between the occurrence of early age related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported, based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, we designed an omics-type approach for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole.<br><br>METHODS: A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For each participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At every position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for each descriptor at every graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure.<br><br>RESULTS: In terms of the amount and disparity of true discoveries, overall non-equivalence was found for early AMD and healthy groups. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise.<br><br>CONCLUSIONS: Between the retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoon and speckle bear essential parts of the total information. We pursued a constructive, completely documented, traceable and repeatable approach without invoking artificial intelligence methods.},
}
@article {pmid39579003,
year = {2025},
author = {Wagner, M and Sommerer, J and Rauscher, FG},
title = {Extracting full information from OCT scans-signs of early age-related macular degeneration within inner retinal layers by local neighbourhood statistics. Part I: Methodology.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {1},
pages = {231-246},
pmid = {39579003},
issn = {1475-1313},
support = {497989466//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; *Macular Degeneration/diagnosis/epidemiology ; Aged ; Case-Control Studies ; *Retina/diagnostic imaging/pathology ; Middle Aged ; Algorithms ; },
abstract = {BACKGROUND AND OBJECTIVES: Associations between the occurrence of early age-related macular degeneration (AMD) and alterations in retinal layer thicknesses have been reported based on classical processing of optical coherence tomography (OCT) data by noise removal and subsequent image segmentation. However, speckle noise within OCT data itself bears a substantial part of the total information. For this reason, an omics-type approach was designed for full exploitation of OCT data, which was able to identify signs of early AMD throughout the retina as a whole.<br><br>METHODS: A nested case-control study was designed with 200 early AMD cases and 200 healthy controls. For every participant, within a randomly selected OCT scan and a randomly selected column therein, manual grading was performed for 26 retinal feature positions. At each position, a total of 3792 descriptors were computed, based on nonlinear transformations of OCT data, first-order neighbourhood statistics and Haralick features. Equivalence and differences between cases and controls were tested for every descriptor at each graded position. Results of multiple testing were expressed in terms of false and true discovery rates controlled by the Benjamini-Yekutieli procedure.<br><br>RESULTS: In terms of the amount and disparity of true discoveries, overall non-equivalence of early AMD and healthy groups was found. Strong difference signals were observed at the internal limiting membrane and two central retinal positions, particularly for descriptors emphasising speckle noise.<br><br>CONCLUSIONS: Between retinae of healthy controls and early AMD patients, significant differences were observed at the level of local neighbourhood statistics within the OCT data. Thus, independent evidence was obtained for AMD affecting not only the outer retinal layers but also the retina as a whole, even in the early stages of the disease. Within OCT data, both cartoons and speckle bear essential parts of total information. A constructive, completely documented, traceable and repeatable approach was pursued without invoking artificial intelligence methods.},
}
@article {pmid39578549,
year = {2025},
author = {Domalpally, A and Haas, AM and Chandra, S and VanderZee, B and S Dimopoulos, I and D L Keenan, T and W Pak, J and G Csaky, K and A Blodi, B and Sivaprasad, S},
title = {Photoreceptor assessment in age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {2},
pages = {284-295},
pmid = {39578549},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/physiopathology/diagnosis/pathology ; *Geographic Atrophy/physiopathology ; *Photoreceptor Cells, Vertebrate/pathology ; Visual Acuity/physiology ; Retinal Pigment Epithelium/pathology ; },
abstract = {Clinical trials investigating drugs for various stages of age-related macular degeneration (AMD) are actively underway and there is a strong interest in outcomes that demonstrate a structure-function-correlation. The ellipsoid zone (EZ), a crucial anatomical feature affected in this disease, has emerged as a strong contender. There is significant interest in evaluating EZ metrics on Optical Coherence Tomography (OCT), such as integrity and reflectivity, as disruption of this photoreceptor-rich layer may indicate disease progression. Loss of photoreceptor integrity in the junctional zone of geographic atrophy (GA) has been shown to exceed the areas of retinal pigment epithelial (RPE) atrophy, thus predicting future GA expansion. Furthermore, reduced visual acuity and retinal sensitivity have been correlated with loss of EZ integrity, underscoring a structure-function relationship. Photoreceptor integrity has also recently been acknowledged by the Food and Drug Administration (FDA), supporting its use as a primary endpoint in clinical trials investigating treatments for GA. However, the segmentation of this EZ still poses challenges. Continuous enhancements in OCT resolution and advancements in automated segmentation algorithms contribute to improved assessment of the EZ, strengthening its potential as an imaging biomarker for assessing photoreceptor function. It remains to be seen whether the EZ will serve as a surrogate marker for intermediate AMD. This article aims to provide an overview of the current understanding and knowledge of the EZ, while addressing ongoing challenges encountered in its assessment and interpretation.},
}
@article {pmid39578546,
year = {2025},
author = {Jamil, MU and Waheed, NK},
title = {Gene therapy for geographic atrophy in age-related macular degeneration: current insights.},
journal = {Eye (London, England)},
volume = {39},
number = {2},
pages = {274-283},
pmid = {39578546},
issn = {1476-5454},
mesh = {Humans ; *Geographic Atrophy/therapy/genetics ; *Genetic Therapy/methods ; *Macular Degeneration/therapy ; },
abstract = {Geographic atrophy (GA) is the advanced stage of non-neovascular (dry) age-related macular degeneration, defined by the presence of sharply demarcated atrophic lesions of the outer retina. The complement system is integral to the body's natural immune response, and hence its overactivation can lead to tissue damage and inflammation. It has been shown to play a significant role in GA lesion development and progression, and therefore, complement inhibition is emerging as a promising avenue for therapeutic intervention. With the recent approval by the Food and Drug Administration of drugs like SYFOVRE™ (pegcetacoplan injection) and IZERVAY™ (avacincaptad pegol intravitreal solution), there is hope for the development of interventions capable of slowing down or arresting the progression of GA. In particular, gene therapy intervention is gaining traction for halting GA atrophy at the source of our genes. The concept is to insert a gene into the eye that will act as an ocular "bio-factory," producing a desired protein. This can either lead to overproduction of an already available protein or produce a substance not typically generated in the eye. This review aims to provide an overview of the present understanding of GA, encompassing risk factors, prevalence, pathophysiology, and genetic associations. It will also highlight the current landscape of GA treatment, with particular emphasis on gene therapy intervention.},
}
@article {pmid39577606,
year = {2025},
author = {Khan, AH and Mulfaul, K},
title = {Choroidal macrophages in homeostasis, aging and age-related macular degeneration.},
journal = {Experimental eye research},
volume = {250},
number = {},
pages = {110159},
doi = {10.1016/j.exer.2024.110159},
pmid = {39577606},
issn = {1096-0007},
mesh = {Humans ; *Macular Degeneration/immunology/physiopathology ; *Homeostasis/physiology ; *Choroid/pathology ; *Aging/physiology ; *Macrophages/immunology/physiology ; Animals ; },
abstract = {With increasing age, the optimal functioning of the choroid is essential for efficient removal of waste products formed from photoreceptor renewal. A decline in regulatory elements of the immune system, termed immunosenescence, and the failure of para-inflammation to restore tissue homeostasis can result in the progression of healthy aging to sight-threatening inflammation of the choroid. Macrophages are uniquely situated between the innate and adaptive immune systems, with a high capacity for phagocytosis, recognition of complement components, as well as antigen presentation. In this review, we provide an overview of macrophages and their properties in the healthy choroid and cover the impact of aging, immunosenescence and inflammaging on the function of choroidal macrophages. We will discuss the impact of age on macrophage phenotype and behaviour in the pathophysiology of age-related macular degeneration.},
}
@article {pmid39575904,
year = {2024},
author = {Fleming, LL and Defenderfer, MK and Demirayak, P and Stewart, P and Decarlo, DK and Visscher, KM},
title = {Impact of Deprivation and Preferential Usage on Functional Connectivity Between Early Visual Cortex and Category-Selective Visual Regions.},
journal = {Human brain mapping},
volume = {45},
number = {17},
pages = {e70064},
pmid = {39575904},
issn = {1097-0193},
support = {F99 NS113424/NS/NINDS NIH HHS/United States ; U01 EY025858/EY/NEI NIH HHS/United States ; NINDS F99NS113424/NH/NIH HHS/United States ; NEI U01EY025858/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Magnetic Resonance Imaging ; Male ; Female ; *Visual Cortex/diagnostic imaging/physiology/physiopathology ; Aged ; Macular Degeneration/physiopathology/diagnostic imaging ; Middle Aged ; Visual Pathways/diagnostic imaging/physiology/physiopathology ; Sensory Deprivation/physiology ; Neuronal Plasticity/physiology ; Brain Mapping ; Aged, 80 and over ; Visual Perception/physiology ; },
abstract = {Human behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how removal of input changes brain function. However, an important question yet to be answered is: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details. When central vision is lost in conditions like macular degeneration, peripheral vision must be relied upon for those everyday tasks, with some portions receiving "preferential" usage over others. Using resting-state fMRI collected during total darkness, we examined how deprivation and preferential usage influence the intrinsic functional connectivity of sensory cortex by studying individuals with selective vision loss due to late stages of macular degeneration. Specifically, we examined functional connectivity between category-selective visual areas and the cortical representation of three areas of the retina: the lesioned area, a preferentially used region of the intact retina, and a non-preferentially used region. We found that cortical regions representing spared portions of the peripheral retina, regardless of whether they are preferentially used, exhibit plasticity of intrinsic functional connectivity in macular degeneration. Cortical representations of spared peripheral retinal locations showed stronger connectivity to MT, a region involved in processing motion. These results suggest that the long-term loss of central vision can produce widespread effects throughout spared representations in early visual cortex, regardless of whether those representations are preferentially used. These findings support the idea that connections to visual cortex maintain the capacity for change well after critical periods of visual development.},
}
@article {pmid39575534,
year = {2024},
author = {Paterson, C and Vargis, E},
title = {Applying low levels of strain to model nascent phenomenon of retinal pathologies.},
journal = {Lab on a chip},
volume = {24},
number = {24},
pages = {5338-5346},
pmid = {39575534},
issn = {1473-0189},
support = {R15 EY028732/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/cytology/pathology ; Swine ; *Macular Degeneration/metabolism/pathology ; Stress, Mechanical ; Cells, Cultured ; Choroidal Neovascularization/metabolism/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in aging populations. A better understanding of the mechanisms of the disease, especially at early stages, could elucidate new treatment targets. One characteristic of AMD is strain on the retinal pigment epithelium (RPE), a crucial layer of the retina. This strain can be caused by physical phenomena like waste aggregation underneath the RPE, drusen formation, or leaky blood vessels that infiltrate the retina during choroidal neovascularization (CNV). It is not well understood how strain affects RPE cell function. Most models generate equibiaxial strain or higher levels of strain that are not representative of early stages of AMD. To overcome these issues, we engineered a device to cause controlled, low amounts of localized, radial strain (maximum ∼1.4%). This strain level is more mimetic to what occurs during aging or at the beginning of physical disruptions experienced during AMD. To evaluate how RPE cells respond to this physical stimulus, primary porcine RPE cells were exposed to low levels of strain applied by our custom-made device. Cell secretions and genetic expression were analyzed to determine how proteins linked to drusen and CNV are affected. The results indicate that this low amount of strain does not immediately initiate angiogenesis but causes changes in mRNA expression of amyloid precursor protein (APP), which plays a role in retinal health and drusen accumulation. This research offers insight into AMD progression as well as the health of other organs, including the brain.},
}
@article {pmid39574566,
year = {2025},
author = {Becker, S and Allen, J and Morison, ZL and Saeid, S and Adderley, A and Koskelainen, A and Vinberg, F},
title = {Healing of ischemic injury in the retina.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.04.621932},
pmid = {39574566},
issn = {2692-8205},
abstract = {UNLABELLED: Neuro- and retinal degenerative diseases, including Alzheimer's, age-related macular degeneration, stroke, and central retinal artery occlusion, rob millions of their independence. Studying these diseases in human retinas has been hindered by the immediate loss of neuronal activity postmortem. While recent studies restored limited activity in postmortem CNS tissues, synchronized neuronal transmission >30 minutes postmortem remained elusive. Our study overcomes this barrier by reviving and sustaining light signal transmission in human retinas recovered up to four hours and stored 48 hours postmortem. We also establish infrared-based ex vivo imaging for precise sampling, a closed perfusion system for drug testing, and an ex vivo ischemia-reperfusion model in mouse and human retina. This platform enables testing of neuroprotective and neurotoxic effects of drugs targeting oxidative stress and glutamate excitotoxicity. Our advances question the irreversibility of ischemic injury, support preclinical vision restoration studies, offer new insights into treating ischemic CNS injuries, and pave the way for transplantation of human donor eyes.<br><br>TEASER: Reviving light signaling in postmortem human retinas challenges the irreversibility of ischemic injury and advances research to restore vision.},
}
@article {pmid39572858,
year = {2025},
author = {Loo, CY and Fenwick, EK and Man, REK and Lamoureux, EL and Tan, ACS},
title = {Utilisation of patient-centred outcome measures in age-related macular degeneration research and clinical practice: A systematic review.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {2},
pages = {161-174},
doi = {10.1111/ceo.14466},
pmid = {39572858},
issn = {1442-9071},
support = {05/FY2016/P2/20-A47//SingHealth/ ; },
mesh = {Humans ; *Macular Degeneration/physiopathology/therapy/diagnosis ; Psychometrics ; *Visual Acuity/physiology ; *Patient Reported Outcome Measures ; *Quality of Life ; *Patient-Centered Care ; },
abstract = {BACKGROUND: To identify the utilisation, type, and psychometric properties of patient-centered outcome measures (PCOMs) associated with the performance-based assessment of visual function (VF) in age-related macular degeneration (AMD) in clinical care and research.<br><br>METHODS: A systematic literature search identified studies, available in English, that used PCOMs to assess VF in patients with any AMD severity, published from January 2015 to November 2023. Two researchers screened studies for quality using the Mixed Methods Appraisal Tool (MMAT) 2018 and assessed the psychometric properties of the PCOMs with the guidance of Consensus-based Standards for the selection of health Measurement Instruments (COSMIN).<br><br>RESULTS: Of 514 studies shortlisted in the literature, 31 were eligible with the majority (77.4%) fulfilling all the MMAT criteria, indicating good quality. The most used PCOM was reading (14/31&#x2009;=&#x2009;45.1%), with 5 of the 14 studies (35.7%) showing that the increasing severity and/or progression of AMD were associated with a worsening reading ability. AMD also negatively affected mobility and physical activity levels (7/31&#x2009;=&#x2009;22.6%), and visual search and exploration (4/31&#x2009;=&#x2009;12.9%). Based on the COSMIN checklist, apart from reading and physical activity measured with the accelerometer, the other PCOMs had 'inadequate' psychometric properties.<br><br>CONCLUSIONS: Limited published studies include PCOMs as an assessment of VF in AMD patients. Apart from reading, there is a lack of robust validation data to support the widespread use of other PCOMs. Hence, well-designed, robustly validated, and simple to use PCOMs are required for more widespread implementation in AMD clinical care and research.},
}
@article {pmid39572693,
year = {2024},
author = {Blaha, V and Rathouska, JU and Langrova, H and Blaha, M and Studnicka, J and Andrys, C and Loefflerova, V and Lanska, M and Vejrazkova, E and Nachtigal, P and Stepanov, A},
title = {Soluble endoglin as a biomarker of successful rheopheresis treatment in patients with age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {28902},
pmid = {39572693},
issn = {2045-2322},
support = {17-29241A//Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky/ ; CZ.02.01.01/00/22_008/0004607//European Union/ ; },
mesh = {Humans ; Aged ; Male ; Female ; *Biomarkers/blood ; *Macular Degeneration/therapy/blood ; *Endoglin/blood ; Treatment Outcome ; Middle Aged ; Visual Acuity ; },
abstract = {Age-related macular degeneration (AMD) is a progressive chronic disease causing visual impairment or central vision loss in the elderly. We hypothesized that successful rheopheresis would be associated with positive changes in soluble endoglin (sENG), PSCK9, alpha-2-macroglobulin (A2M), and hs-CRP levels. 31 elderly patients with the dry form of AMD, treated with rheopheresis with a follow-up period of at least 5 years and an average age of 68 ± 4 years, were evaluated. Each treated patient received a series of 8 procedures in 10 weeks and, after the 2-year period, another 2 procedures within 1 week. Then, the patients were followed up every 6 months and divided into the successfully treated and therapeutic failure group according to best-corrected visual acuity (BCVA), size of the drusen area, and the drusenoid pigment epithelium detachment (DPED). Based on the ophthalmological assessment, rheopheresis treatment was successful in 73% of AMD patients. The therapy was associated with a significant decrease in total cholesterol, LDL-C, HDL-C, apoprotein B, lipoprotein (a) levels, and rheologically important parameters, irrespective of the therapy's success or failure. The success of rheopheresis therapy was exclusively related to a significant decrease in sENG and A2M levels. Over the long term, rheopheresis prevented the decline of BCVA, reduced the DPED and area of macular drusen, and improved the preservation of an intact photoreceptor ellipsoid zone in most patients. Moreover, we showed for the first time that sENG and A2M could be potentially sensitive biomarkers of successful rheopheresis procedure, irrespective of lipid parameters changes.},
}
@article {pmid39571793,
year = {2025},
author = {Borkar, D and Rahimy, E and Khan, MA and Ho, AC and Hatfield, M and Nguyen, TH and Jones, D and Fineman, MS and McKeown, A and Leng, T and Baumal, CR and Holekamp, N},
title = {Functional Outcomes and Quality of Life in Geographic Atrophy in the Clinical Setting.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {3},
pages = {299-301},
doi = {10.1016/j.oret.2024.11.013},
pmid = {39571793},
issn = {2468-6530},
}
@article {pmid39571776,
year = {2025},
author = {Carozza, G and Zerti, D and Pulcini, F and Lancia, L and Delle Monache, S and Mattei, V and Maccarone, R},
title = {Conditioned media from dental pulp stem cells to counteract age-related macular degeneration.},
journal = {Experimental eye research},
volume = {250},
number = {},
pages = {110167},
doi = {10.1016/j.exer.2024.110167},
pmid = {39571776},
issn = {1096-0007},
mesh = {Culture Media, Conditioned/pharmacology ; *Dental Pulp/cytology ; Rats ; Animals ; *Macular Degeneration/prevention &amp; control/metabolism/pathology ; *Stem Cells ; *Disease Models, Animal ; Cells, Cultured ; Intravitreal Injections ; Male ; Rats, Wistar ; Humans ; Retinal Pigment Epithelium/metabolism/pathology/drug effects ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. To date, there are no effective therapies to counteract AMD towards the most severe stages characterised by a progressive loss of photoreceptors triggered by retinal pigmented epithelium dysfunction. Given their easy source and their high proliferative potential, Dental Pulp Stem Cells (DPSCs) are considered promising for regenerative medicine. The main advantage of DPSCs is related to their paracrine immunosuppressive and immunoregulatory abilities, including the capability to promote regeneration of damaged tissues. Recent studies demonstrated the therapeutic potential of DPSCs-conditioned media (CM) in neurodegenerative diseases. In addition, we have already shown a differential expression of some growth factors and cytokines in CM derived from DPSCs cultured in hypoxia and normoxia conditions.<br><br>AIM: In this study we evaluated the capability of DPSCs-CM to counteract retinal degeneration in an animal model of AMD. DPSCs-CM were intravitreally injected the day before the exposure of albino rats to high intensity light (LD).<br><br>RESULTS: We evaluated the retinal function, and we performed morphological and molecular analysis a week after the LD, in accordance with the well-established protocol of our light damage model. DPSCs-CM obtained from hypoxia (HYPO-CM) or normoxia (NORM-CM), were able to preserve the retinal function, to reduce the damaged area and to counteract the upregulation of key factors involved in retinal degeneration, like FGF-2. Furthermore, we demonstrated that neither conditioned media modified inflammatory activation, as shown by both microglia activation and GFAP upregulation, but in vitro studies demonstrated a significant effect of both CM to counteract oxidative stress, one of the main causes of AMD.<br><br>CONCLUSION: Taken together, our study demonstrated that NORM-CM and HYPO-CM, albeit with a different chemical composition, could represent eligible candidates to counteract retinal degeneration in an animal model of AMD. Further studies are needed to obtain conditioned media with the best performance in term of retinal protection.},
}
@article {pmid39571557,
year = {2025},
author = {García-Layana, A and Chi, GC and Kodjikian, L and Parravano, M and Chow, D and Jackson, TL and Danzig, C and Paris, LP and Mirt, M and Henry-Szatkowski, M and Lewis, HB and Gentile, B},
title = {Patient Preferences with Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Multinational Discrete Choice Experiment Study.},
journal = {Ophthalmic research},
volume = {68},
number = {1},
pages = {13-22},
pmid = {39571557},
issn = {1423-0259},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Diabetic Retinopathy/drug therapy/complications/psychology/diagnosis ; Intravitreal Injections ; *Macular Edema/drug therapy/etiology ; *Patient Preference ; Ranibizumab/administration &amp; dosage ; Surveys and Questionnaires ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {INTRODUCTION: New anti-vascular endothelial growth factor (VEGF) treatments are emerging for the treatment of diabetic macular edema (DME)/neovascular age-related macular degeneration (nAMD). This study aimed to explore the treatment attributes patients find important when deciding on treatment options.<br><br>METHODS: This noninterventional survey study assessed treatment preferences through a discrete choice experiment (DCE) among patients with DME/nAMD in the USA, Canada, France, Italy, Spain, and the UK. The DCE design was informed by a targeted literature review and qualitative interview research and included five treatment attributes: mode of administration, frequency of examinations, frequency of injections or refills, likely change in visual acuity, and eye-related side effects. Conditional logit models were used to analyze the choice data.<br><br>RESULTS: Overall, 537 patients completed the DCE (DME, n = 173; nAMD, n = 364). Patients reported preferring "injection" over "implant surgery and refills" and better visual outcomes over "stabilization," which were also the most important attributes driving preference (35.1% and 31.5%, respectively). They also showed a preference for less-frequent treatment and examinations and for "mild-moderate, frequent" over "severe, rare" side effects. These findings were generally consistent across the two conditions, although significant differences were found depending on anti-VEGF treatment duration (nAMD, DME) and number of reported barriers (nAMD).<br><br>CONCLUSION: Patient preferences for treatment are driven by several factors. Considering these preferences is essential when designing/introducing new therapies. Individual treatment preferences should be identified and given key consideration when helping patients select from an expanding array of treatment options.},
}
@article {pmid39569789,
year = {2024},
author = {Kulikov, AN and Kalinicheva, YA and Maltsev, DS},
title = {[Efficacy of brolucizumab in the treatment of retinal pathologies: a review of post-marketing studies].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {5},
pages = {154-161},
doi = {10.17116/oftalma2024140051154},
pmid = {39569789},
issn = {0042-465X},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; *Diabetic Retinopathy/drug therapy ; Treatment Outcome ; Intravitreal Injections ; Product Surveillance, Postmarketing/methods ; Macular Edema/drug therapy/etiology ; Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {Brolucizumab, an angiogenesis inhibitor, is a single-chain fragment of a humanized antibody used to treat neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Although registration studies are the primary source of information on the new drug, post-marketing studies allow for further exploration and expansion of previous knowledge about its effectiveness, safety, and dosing regimens. This study summarizes the experience with brolucizumab from real-world clinical practice studies. A systematic literature review was conducted to identify articles published up to April 2024 that investigated the use of brolucizumab in the treatment of retinal vasogenic diseases, revealing the high effectiveness of brolucizumab compared to other angiogenesis inhibitors in the treatment of patients with nAMD and DME, including those who were treatment-naïve and those resistant to ongoing therapy, as well as patients with changes in the vitreoretinal interface. A significant advantage of brolucizumab is its ability to reduce the number of injections and extend the intervals between them up to 16 weeks. Study results demonstrate substantial improvements in anatomical and functional outcomes compared to previously existing and newly emerging angiogenesis inhibitors. Its ability to stabilize disease progression, achieve better disease control, and reduce injection frequency makes brolucizumab an attractive option for both first-line therapy and as a switching drug, highlighting its potential for expanded indications.},
}
@article {pmid39568745,
year = {2024},
author = {Wang, Q and Cai, S},
title = {Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1460779},
pmid = {39568745},
issn = {2296-858X},
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of low vision and even blindness in the elderly population worldwide. However, no studies have been conducted to analyze the causal relationship between the cathepsin family and AMD. The present study aimed to explore and analyze this potential association using Mendelian randomization (MR).<br><br>METHODS: In this study, AMD was classified into two types: exudative AMD and atrophic AMD. Inverse-variance weighting (IVW) was used as the main analysis method. The association between nine cathepsins and the two classifications of AMD were analyzed using multivariable Mendelian randomization (MVMR). Sensitivity analysis included Cochran's Q-test and the MR-Egger intercept test.<br><br>RESULTS: Two-sample MR analysis showed that higher levels of cathepsin L2 were associated with a delay in the development of atrophic AMD (IVW: p&#x2009;=&#x2009;0.017; OR&#x2009;=&#x2009;0.885; 95% CI&#x2009;=&#x2009;0.799-0.979). Reverse MR analysis indicated that cathepsin E levels were increased in individuals with atrophic (IVW: p&#x2009;=&#x2009;0.023; OR&#x2009;=&#x2009;1.058; 95% CI&#x2009;=&#x2009;1.007-1.111) and exudative AMD (IVW: p&#x2009;=&#x2009;0.018; OR&#x2009;=&#x2009;1.061; 95% CI 1&#x2009;=&#x2009;1.010-1.115). MVMR analysis indicated a causal relationship between cathepsin G (IVW: p&#x2009;=&#x2009;0.025; OR&#x2009;=&#x2009;1.124; 95% CI&#x2009;=&#x2009;1.014-1.245), cathepsin O (IVW: p&#x2009;=&#x2009;0.043, OR&#x2009;=&#x2009;1.158, 95% CI&#x2009;=&#x2009;1.004-1.336), and exudative AMD after coordinating for other types of cathepsin.<br><br>CONCLUSION: This study demonstrated a potential link between the cathepsin family and the onset of AMD. Elevated serum concentrations of cathepsin L2 may serve as a protective factor for atrophic AMD, while increased levels of serum cathepsin G and O concentrations may promote the development of exudative AMD. Besides, the development of AMD may be associated with elevated serum concentrations of cathepsin E.},
}
@article {pmid39567706,
year = {2025},
author = {Patwardhan, A and Ali, N and Law, S},
title = {Intravitreal Faricimab in treatment-naïve neovascular age-related macular degeneration: real-world outcome of 12-week extension after the loading dose from a UK centre.},
journal = {Eye (London, England)},
volume = {39},
number = {4},
pages = {766-770},
pmid = {39567706},
issn = {1476-5454},
mesh = {Humans ; Female ; Intravitreal Injections ; Retrospective Studies ; Male ; Aged ; *Visual Acuity ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged, 80 and over ; Treatment Outcome ; United Kingdom ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Antibodies, Bispecific ; },
abstract = {OBJECTIVES: To assess the visual outcome of extension to 12-weekly intervals (Q12W) following 4 loading doses of intravitreal Faricimab injections as described in the TENAYA and LUCERENE trials for the management of treatment-naïve neovascular Age-related Macular Degeneration (nAMD).<br><br>METHODS: A retrospective analysis was carried out on all treatment-na&#xef;ve nAMD patients who started Faricimab intravitreal injections in the period between 1[st] September 2022 and 31[st] January 2023. The data collection included best corrected visual acuity (BCVA) at baseline, 12 weeks, 24 weeks and 52 weeks; Central Subfield Thickness (CST) at baseline, 24 weeks and 52 weeks; Number of injections at 52 weeks; treatment intervals at 52 weeks. Descriptive and correlational analysis, independent and Paired-sample T-tests were used to analyse the data.<br><br>RESULTS: Sixty-eight eyes completed the one-year of treatment. The mean (SD) age was 79.9 (8.7) years and 61.8% were females. The mean (SD) number of injections at 52 weeks was 6.8 (0.8). The BCVA improved from baseline by a mean (SD) of 7.0 (10.8) letters at 12 weeks (p&#x2009;<&#x2009;0.001), 7.3 (12.1) letters at 24 weeks (p&#x2009;<&#x2009;0.001) and 8.2 (13.4) letters at 52 weeks (p&#x2009;<&#x2009;0.001). The mean (SD) reduction in CST was 114.8 (SD 122.8) microns at 24 weeks (p&#x2009;<&#x2009;0.001), and 89.4 (121.9) microns at 52 weeks (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: A Q12W approach following 4 loading doses of Faricimab for the treatment of nAMD in real-world achieves excellent visual outcomes comparable to pivotal trial with optimum number of injections in the first year.},
}
@article {pmid39566885,
year = {2025},
author = {Sacconi, R and Forte, P and Corradetti, G and Costanzo, E and Capuano, V and Bousquet, E and Beretta, F and Iannuzzi, S and Polito, MS and Nicolò, M and Parravano, M and Souied, E and Sarraf, D and Sadda, S and Bandello, F and Querques, G},
title = {Type 3 Macular Neovascularization in Age-related Macular Degeneration: Baseline Predictors of 3-Year Macular Atrophy Development.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {6},
pages = {546-555},
doi = {10.1016/j.oret.2024.11.011},
pmid = {39566885},
issn = {2468-6530},
mesh = {Humans ; Female ; Retrospective Studies ; Male ; *Tomography, Optical Coherence/methods ; Follow-Up Studies ; *Wet Macular Degeneration/diagnosis/complications/drug therapy ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; *Fluorescein Angiography/methods ; *Macula Lutea/pathology ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Aged, 80 and over ; Ranibizumab/administration &amp; dosage ; Time Factors ; },
abstract = {PURPOSE: To identify baseline OCT predictors of the 3-year macular atrophy (MA) development for type 3 (T3) macular neovascularization (MNV) secondary to neovascular age-related macular degeneration (nAMD) treated by anti-VEGF therapy.<br><br>DESIGN: Multicenter, retrospective, longitudinal study.<br><br>PARTICIPANTS: We included patients with treatment-naive T3 MNV secondary to nAMD at baseline, treated with anti-VEGF during a 3-year follow-up.<br><br>METHODS: Patients were identified from 6 retinal referral institutions: (1) San Raffaele University, Milan, Italy; (2) University of Genova, Genova, Italy; (3) Doheny Eye Institute, Los Angeles; (4) Stein Eye Institute, Los Angeles; (5) University of Paris Est, Creteil, France; and (6) Istituto di Ricovero e Cura a Carattere Scientifico Bietti Foundation, Rome, Italy. Several baseline predictors of 3-year MA area were analyzed based on structural OCT and demographics.<br><br>MAIN OUTCOME MEASURES: Multivariate analysis to identify baseline independent predictors of the 3-year MA development for T3 MNV secondary to nAMD treated by anti-VEGF therapy.<br><br>RESULTS: We included 131 eyes of 131 patients (mean age, 80 &#xb1; 6 years; 81% females). Best-corrected visual acuity was 0.49 &#xb1; 0.40 logarithm of the minimum angle of resolution (logMAR) at the baseline and significantly decreased to 0.59 &#xb1; 0.43 logMAR at the end of 3-year follow-up (P < 0.001). Patients were treated with 11 &#xb1; 6 anti-VEGF injections and developed atrophy in 75% of cases (from 18% at the baseline). Eyes that developed 3-year MA were treated with a significantly lower number of injections compared with eyes without MA (9.9 &#xb1; 5.5 vs. 14.7 &#xb1; 7.2 injections, P < 0.001). The most relevant independent predictors at baseline of MA area at 3-year follow-up were: area of MA at baseline (P < 0.001), age-related macular degeneration phenotype (presence of reticular pseudodrusen) (P = 0.017), baseline presence of nascent geographic atrophy (P = 0.008), and the baseline presence of subretinal hyperreflective material (P = 0.002).<br><br>CONCLUSIONS: Macular atrophy development is a frequent complication of T3 MNV treated with anti-VEGF injections. Several factors could be considered baseline predictors of atrophy development during the anti-VEGF treatment.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid39566751,
year = {2025},
author = {França Dias, M and Ken Kawassaki, R and Amaral de Melo, L and Araki, K and Raphael Guimarães, R and Ligorio Fialho, S},
title = {Optimizing Retinal Imaging: Evaluation of ultrasmall TiO2 nanoparticle- fluorescein conjugates for improved Fundus Fluorescein Angiography.},
journal = {Methods (San Diego, Calif.)},
volume = {233},
number = {},
pages = {30-41},
doi = {10.1016/j.ymeth.2024.11.012},
pmid = {39566751},
issn = {1095-9130},
mesh = {*Fluorescein Angiography/methods ; *Titanium/chemistry ; Animals ; *Fluorescein/chemistry ; *Retina/diagnostic imaging/drug effects ; *Nanoparticles/chemistry ; Humans ; Contrast Media/chemistry ; Electroretinography/methods ; },
abstract = {Fundus Fluorescein Angiography (FFA) has been extensively used for the identification, management, and diagnosis of various retinal and choroidal diseases, such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, among others. This exam enables clinicians to evaluate retinal morphology and the pathophysiology of retinal vasculature. However, adverse events, including from mild to severe reactions to sodium fluorescein, have been reported. Titanium dioxide nanoparticles (NPTiO2) have shown significant potential in numerous biological applications. Coating or conjugating these nanoparticles with small molecules can enhance their stability, photochemical properties, and biocompatibility, as well as increase the hydrophilicity of the nanoparticles, making them more suitable for biomedical applications. This work demonstrates the potential use of ultrasmall titanium dioxide nanoparticles conjugated with sodium fluorescein to improve the quality of angiography exams. The strategy of conjugating fluorescein with NPTiO2 successfully enhanced the fluorescence photostability of the contrast agent and increased its retention time in the retina. Preliminary in vivo and in vitro safety tests suggest that these nanoparticles are safe for the intended application demonstrating low tendency to hemolysis, and no significant changes in the retina thickness or in the electroretinography a-wave and b-wave amplitudes. Overall, the conjugation of fluorescein to NPTiO2 has produced a nanomaterial with favorable properties for use as an innovative contrast agent in FFA examinations. By providing a clear description of our methodology of analysis, we also aim to offer better perspectives and reproducible conditions for future research.},
}
@article {pmid39565329,
year = {2024},
author = {Mukherjee, S and Duic, C and De Silva, T and Keenan, TDL and Thavikulwat, AT and Chew, EY and Cukras, C},
title = {Automated Detection of Drusenoid Pigment Epithelial Detachments From Spectral-Domain Optical Coherence Tomography in Patients With AMD.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {11},
pages = {25},
pmid = {39565329},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Detachment/diagnostic imaging/pathology ; Female ; Aged ; Male ; *Algorithms ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Retinal Drusen/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; Aged, 80 and over ; Middle Aged ; Bruch Membrane/pathology/diagnostic imaging ; },
abstract = {PURPOSE: This study aimed to develop an algorithm for automated detection of drusenoid pigment epithelial detachments (DPEDs) in optical coherence tomography (OCT) volumes of patients with age-related macular degeneration (AMD) and to compare its performance against traditional reading center grading on color-fundus photographs (CFPs).<br><br>METHODS: Eyes with a range of AMD severities, excluding neovascular disease, were imaged using spectral-domain OCT (SD-OCT) and paired CFPs and were followed annually for up to 5&#xa0;years. DPEDs were automatically identified by segmenting the retinal pigment epithelium (RPE) and Bruch's membrane (BM) layers from the SD-OCT volumes and imposing both a minimum RPE BM height (>75 &#xb5;m) and a two-dimensional length requirement (>433 &#xb5;m). Comparisons in detection rates and contoured areas were made between the algorithmic SD-OCT detections and manually graded and contoured CFPs.<br><br>RESULTS: Of the 1602 visits for the 323 eyes, the automated OCT algorithm identified 139 visits (8.7%) from 50 eyes with DPED, but a reading center review of paired CFPs identified 23 visits (1.4%) from nine eyes as having DPEDs. Eyes identified with DPEDs on OCT received nine-step AMD severity scores ranging from 6 to 10, and those scores had occurrence ratios of 23/160 (14%), 89/226 (39%), 24/99 (24%), 2/63 (3%), and 1/29 (3%), respectively. On a subset of 25 visits that also underwent manual contouring of DPED lesions in CFP, the Pearson correlation coefficient for DPED areas observed by OCT and CFP was 0.85.<br><br>CONCLUSIONS: Our analysis shows the feasibility of using OCT scans to objectively detect features that historically have been detected qualitatively by expert graders on CFPs.<br><br>TRANSLATIONAL RELEVANCE: Automated detection and quantitation of high-risk features can facilitate screening patients for clinical-trial enrollment and could serve as an outcome metric [T1 (Translation-to-Humans) and T4 (Translation-to-Population-Health)].},
}
@article {pmid39563963,
year = {2024},
author = {Sanders, FWB and John, R and Jones, P and Williams, GS},
title = {A Novel Optometry-Led Decision-Making Community Referral Refinement Scheme for Neovascular Age-Related Macular Degeneration Screening.},
journal = {Clinical optometry},
volume = {16},
number = {},
pages = {293-299},
pmid = {39563963},
issn = {1179-2752},
abstract = {BACKGROUND: The prevalence of neovascular age-related macular degeneration (nAMD) continues to increase. Hospital Eye Services are operating above capacity, innovative solutions to minimise the high proportion of false negative referrals, improve the care pathway and increase capacity for those patients who need ongoing care are essential are essential.<br><br>METHODS: A two-phase retrospective longitudinal analysis of all patients referred and assessed for nAMD between; April 2019 to March 2020 (Phase 1) n=394, and April 2020 to March 2021 (Phase 2) n= 414, within Swansea Bay University Health Board (SBUHB). All patients with suspect nAMD were referred to the hospital based nAMD clinic in phase 1, and a community optometry nAMD decision making pathway in phase 2. All clinical records were reviewed, and data collated for subsequent analysis. Age, sex, date of referral, diagnosis, and treatment date were all recorded and analysed.<br><br>RESULTS: During phase 1, 104 new nAMD cases needing treatment were diagnosed with 85% (n=88) receiving treatment within 2&#xa0;weeks of initial referral. During phase 2, 230 new nAMD cases requiring treatment were diagnosed with 94% (n=216) receiving treatment within 2&#xa0;weeks of initial referral. Both the proportion of nAMD cases diagnosed (&#x3c7;&#xb2; = 70.8; p<0.001) and proportion of those treated within 2&#xa0;weeks of initial diagnosis (&#x3c7;&#xb2; = 7.57; p<0.05) were significantly higher during phase 2.<br><br>CONCLUSION: There are advantages to a community optometry nAMD decision-making pathway with regard to 1) decreasing the number of patients requiring HES attendance, 2) increasing the number of patients able to access treatment for nAMD within 2&#xa0;weeks of initial referral 3) an increased rate of diagnosis confirmation of nAMD and 4) a decrease in the rate of false-positive referrals.},
}
@article {pmid39563807,
year = {2024},
author = {Sabnis, RW},
title = {Novel Plasma Kallikrein Inhibitors for Treating Multiple Diseases.},
journal = {ACS medicinal chemistry letters},
volume = {15},
number = {11},
pages = {1808-1809},
pmid = {39563807},
issn = {1948-5875},
abstract = {Provided herein are novel plasma kallikrein inhibitors, pharmaceutical compositions, use of such compounds in treating hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion and processes for preparing such compounds.},
}
@article {pmid39560702,
year = {2025},
author = {Chakraborty, D and Sinha, TK and Sinha, S and Maiti, A and Mukherjee, A and Nandi, K and Das, S and Majumdar, S and Rungta, D and Bhattacharya, R},
title = {Pooled Multicenter Safety Analysis of Lupin's Intravitreal Biosimilar Ranibizumab (Ranieyes) in Chorioretinal Vascular Diseases.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {1},
pages = {129-139},
pmid = {39560702},
issn = {2193-8245},
abstract = {INTRODUCTION: This study aims to evaluate the ocular and systemic safety profiles of intravitreal biosimilar ranibizumab Ranieyes (Lupin Pharmaceuticals, Mumbai, India) in real-world clinical settings across multiple chorioretinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) in adults.<br><br>METHODS: We conducted a retrospective, consecutive, interventional, uncontrolled multicenter study using data from three hospital networks in India. A total of 1401 eyes received 2194 injections of Ranieyes between June 2022 and November 2023. Patients were followed for a minimum of 6&#xa0;months, and data on ocular and systemic adverse events (AEs) were collected and analyzed.<br><br>RESULTS: The study population included 636 male patients and 533 female patients, with a mean age of 58.63&#x2009;&#xb1;&#x2009;11.54&#xa0;years. The average number of injections per eye was 1.49&#x2009;&#xb1;&#x2009;0.23, with the highest frequency in the nAMD group (mean of 2.3&#x2009;&#xb1;&#x2009;0.23 injections per eye) over 6&#xa0;months. Non-serious adverse events (nsAEs) were observed in 26.83% of injections, with mild ocular pain and transient blurring of vision being the most common. Serious ocular adverse events were rare, occurring in 0.85% of eyes, with retinal pigment epithelial tear (RPE TEAR) being the most frequent. Systemic adverse events were noted in 5.03% of patients, and all but one were non-serious. One patient developed non-fatal myocardial infarction, the causal relationship of which, however, was not established with the intravitreal agent used. No cases of endophthalmitis were observed.<br><br>CONCLUSIONS: This large-scale, real-world study demonstrates that Ranieyes is a safe intravitreal antivascular endothelial growth factor (anti-VEGF) agent across various chorioretinal vascular diseases. The safety profile of Ranieyes is consistent with that of the reference product, making it a viable option in resource-constrained settings.},
}
@article {pmid39560628,
year = {2024},
author = {Sadeghi, E and Valsecchi, N and Ibrahim, MN and Du, K and Davis, E and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Chhablani, J},
title = {Three-Dimensional Choroidal Vessels Assessment in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {13},
pages = {39},
pmid = {39560628},
issn = {1552-5783},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/blood supply/diagnostic imaging/pathology ; *Tomography, Optical Coherence/methods ; Male ; Female ; Retrospective Studies ; Aged ; *Imaging, Three-Dimensional ; Cross-Sectional Studies ; Aged, 80 and over ; Middle Aged ; Macular Degeneration/diagnosis ; Visual Acuity/physiology ; Algorithms ; Retinal Vessels/diagnostic imaging/pathology ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To compare the choroidal vasculature in eyes with early- and intermediate-stage age-related macular degeneration (dAMD) and healthy using a novel three-dimensional algorithm.<br><br>METHODS: Patients with dAMD and healthy controls underwent clinical examinations and swept-source optical coherence tomography scans (PlexElite-9000 device) centered on the fovea. Scans with quality scores >6 were included. Eyes with any signs of neovascular AMD or geographic atrophy were excluded. The choroidal layer was segmented using ResUNet model and volumetric smoothing. Phansalkar thresholding was used to binarize the choroidal vasculature. The three-dimensional maps were divided into five sectors. The three largest vessels in each sector were measured to determine the mean choroidal vessel diameter (MChVD) and inter-vessel distance (IVD). Volumetric choroidal thickness (ChT) and vascularity index (CVI) were also calculated.<br><br>RESULTS: This retrospective cross-sectional study analyzed 60 eyes from 45 dAMD patients (27 early-stage, 33 intermediate-stage) and 26 eyes from 16 healthy controls. The average MChVD was increased in dAMD eyes compared to healthy eyes (239.559 &#xb1; 47.058 &#xb5;m vs. 197.873 &#xb1; 49.047 &#xb5;m, P < 0.001). The average MChVD in each sector increased significantly in eyes with dAMD (P < 0.05). The average IVD was increased significantly in dAMD eyes compared to healthy eyes (234.128 &#xb1; 69.537 &#xb5;m vs. 179.914 &#xb1; 49.995 &#xb5;m, P < 0.001). The average IVD in each sector was significantly increased in eyes with dAMD (P < 0.05). Average ChT and CVI in dAMD were reduced compared to healthy eyes (P < 0.05).<br><br>CONCLUSIONS: Eyes with dAMD demonstrated increased MChVD and IVD and decreased ChT and CVI, possibly related to smaller-vessel atrophy and larger-vessel dilation.},
}
@article {pmid39560583,
year = {2024},
author = {Meng, M and Shen, X and Xie, Y and Wang, J and Liu, J},
title = {The association between age-related macular degeneration and risk of Parkinson disease: A systematic review and meta-analysis.},
journal = {Medicine},
volume = {103},
number = {46},
pages = {e40524},
pmid = {39560583},
issn = {1536-5964},
support = {2023HT033//China University Industry-Academia-Research Innovation Fund--Huatong Guokang Medical Research Project/ ; 242102311250//2024 Henan Provincial Science and Technology Project/ ; HSEP-DFCTCM-2023-8-45, HSEP-DFCTCM-2023-8-27//Construction of the Double First-Class Traditional Chinese Medicine Discipline Project in Henan Province--Cultivating the Innovation Ability of Graduate Students/ ; },
mesh = {Humans ; *Parkinson Disease/epidemiology/etiology ; *Macular Degeneration/epidemiology/etiology ; Risk Factors ; },
abstract = {BACKGROUND: Numerous cohort studies have explored the association between age-related macular degeneration (AMD) and Parkinson disease (PD). However, a comprehensive meta-analysis on this topic is currently lacking. This study aims to address this gap by conducting a meta-analysis of existing cohort studies to investigate the relationship between AMD and the risk of developing PD.<br><br>METHODS: Relevant studies were systematically identified through thorough searches of the PubMed, Web of Science, Embase, and Cochrane Library databases. Two investigators independently conducted data extraction. Cohort studies meeting the eligibility criteria and providing risk and precision estimates regarding AMD and the risk of PD were included. Pooled hazard ratio (HR) accompanied by 95% confidence interval (CI) were calculated using either a random-effects model or a fixed-effects model. Sensitivity analyses, involving the exclusion of 1 study at a time, were performed to assess the robustness of the findings. Publication bias was evaluated using Egger test.<br><br>RESULTS: Five studies were included, encompassing a total of 4,771,416 individuals. Among these, 128,771 individuals had AMD, while 4,642,645 individuals did not. The pooled analysis revealed a significant increase in the risk of developing PD for individuals with age-related macular degeneration (hazard ratio [HR]&#x2005;=&#x2005;1.44; 95% confidence interval [CI]: 1.22-1.71; I2 = 47.3%). Sensitivity analysis confirmed the robustness of the results. For the exploration of the relationship between nAMD and the risk of developing PD, 2 cohorts were included. The pooled analysis demonstrated a significantly elevated risk of PD for individuals with nAMD (HR&#x2005;=&#x2005;2.21; 95% CI: 1.55-3.16; I2&#x2005;=&#x2005;0%).<br><br>CONCLUSION: This meta-analysis suggests a significant association between AMD and an increased risk of PD. These findings offer fresh perspectives on PD's etiology and pathogenesis, but should be interpreted with caution given the limitations in establishing causality.},
}
@article {pmid39560148,
year = {2024},
author = {Malvasi, M and Calandri, A and Pacella, E and Vingolo, EM},
title = {Effects on corneal endothelium of intravitreal injection of anti-VEGF drugs.},
journal = {Cutaneous and ocular toxicology},
volume = {43},
number = {4},
pages = {369-382},
doi = {10.1080/15569527.2024.2422914},
pmid = {39560148},
issn = {1556-9535},
mesh = {Humans ; *Intravitreal Injections ; *Endothelium, Corneal/drug effects/pathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Aged ; Female ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Macular Degeneration/drug therapy ; Bevacizumab/administration &amp; dosage ; Aged, 80 and over ; Ranibizumab/administration &amp; dosage/therapeutic use ; Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use/adverse effects ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Retinal Vein Occlusion/drug therapy ; Adult ; },
abstract = {PURPOSE: Intravitreal drug administration has become the gold standard for the treatment of many retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinal vein occlusion (RVO). The frequency of this procedure has increased significantly after the introduction of anti-VEGF drugs, since the rise in the average age of the population, which is closely correlated with these diseases. In order to ensure therapeutic success in these patients with chronic retinal diseases, intravitreal treatment with anti-VEGF requires a long-term maintenance regimen with repeated administrations. For this reason today, we must consider the risks linked to complications associated with the long-term application of this therapy. Our study aims to investigate whether the intravitreal injection of anti-VEGF may lead to damage to the corneal endothelium, either directly through the administration procedure or indirectly due to the drug's toxicity. We aimed to establish a clear correlation between intravitreal drug administration and a statistically significant reduction in corneal endothelial cell count in the treated eye when compared to the untreated eye. The study also sought to assess whether different toxicities might be present between different types of drugs belonging to the same anti-VEGF family.<br><br>MATERIALS AND METHODS: The study was conducted by examining a cohort of 133 patients suffering from different diseases: AMD, EMD and RVO. All patients underwent measurement of the endothelial count with CellChek[&#xae;] 20, considering the value measured at the first injection as time zero and reassessed at each subsequent treatment session. The measurement of the endothelial count was performed both on the eye under treatment (TE) and in the eye not undergoing intravitreal injection (NTE) with anti-VEGF drugs for each injection cycle. Different anti-VEGF drugs such as Bevacizumab, Ranibizumab, Aflibercept, Brolucizumab were used for intravitreal therapy. The test patients were included in a 12-month follow-up programme, in which the measurement intervals are dictated by the treatment plan.<br><br>RESULTS: The statistical analysis performed on the corneal endothelial cell counts showed that the ECD (endothelial cell density) parameter decreases with each administration of the drug. The analysis of the difference in the mean endothelial cell counts of the TE reveals that the difference in the number of endothelial cells between the first and second counts in TE is 54.00; greater than the difference in the number of cells found in NTE, which was 13.42. Both the difference between the TE and NTE cell counts are statistically significant. In the case of the TE, the p-value is <0.001, while in the case of the NTE the p-value is still significant as <0.05. The hypothesis that the different types of anti-VEGF drugs could determine the decrease in endothelial cell count differently was also evaluated. No statistically significant data emerged from the analyses (p-value is >0.05).<br><br>CONCLUSIONS: The study demonstrated a statistically significant reduction of corneal endothelial cells in patients undergoing intravitreal injection treatment per number of injections with anti-VEGF, this reduction being independent of the type of anti-VEGF used (Bevacizumab, Ranibizumab, Aflibercept and Brolucizumab).},
}
@article {pmid39559550,
year = {2024},
author = {Milan, S and Pastore, MR and Gaggino, A and Rinaldi, S and Tognetto, D},
title = {Exudative perifoveal vascular anomalous complex (ePVAC) resembling lesion in a patient with adult-onset foveomacular vitelliform dystrophy.},
journal = {American journal of ophthalmology case reports},
volume = {36},
number = {},
pages = {102211},
pmid = {39559550},
issn = {2451-9936},
abstract = {PURPOSE: to report a case of exudative perifoveal vascular anomalous complex (ePVAC) in a patient with adult-onset foveomacular vitelliform dystrophy.<br><br>OBSERVATIONS: A 71-year-old male presented with moderate vision loss in his left eye. His past medical and ocular history were unremarkable. The best-corrected visual acuity was 20/32. Fundus examination disclosed the presence of a perifoveal vascular abnormality, associated with a small egg-yolk lesion. Optical coherence tomography (OCT) scan passing through the perifoveal vascular abnormality seen on fundus, revealed a small round hyperreflective lesion located at the outer plexiform layer-inner nuclear layer, surrounded by intraretinal cysts. Fluorescein angiography displayed an isolated perifoveal aneurysmal lesion with minimal leakage. OCT angiography permitted to localize the lesion flow signal at the deep capillary plexus (DCP) and the avascular slab; choriocapillaris structure was unaffected; any retino-choroidal anastomosis was detected. A systemic workup was suggested to rule out any vascular diseases, and any abnormality was found. He was thus diagnosed with ePVAC. A stability of the clinical picture was demonstrated after 3 months of follow up.<br><br>CONCLUSION: ePVAC has recently been described to appear in association with other macular abnormalities, such as age-related macular degeneration and myopic macular degeneration. Our case firstly demonstrates an ePVAC lesion in an eye with adult-onset foveomacular vitelliform dystrophy. This observation highlights the importance of discerning between different vascular disorders of the macula, to offer the right treatment to the patient.},
}
@article {pmid39559315,
year = {2024},
author = {Ma, JX and Zhang, ZY and Di, R and Yang, JJ and Tian, SW and Qin, YZ and Zhang, WH and Lei, JQ and Liu, QP and Li, JM},
title = {Comparative study between swept-source and spectral-domain OCTA for imaging of choroidal neovascularization in age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {17},
number = {11},
pages = {2067-2073},
pmid = {39559315},
issn = {2222-3959},
abstract = {AIM: To compare the differences of choroidal neovascularization (CNV) measurements between swept-source and spectral-domain optical coherence tomography angiography (SS-OCTA and SD-OCTA) in neovascular age-related macular degeneration (nAMD) and the imaging reliability of the two devices.<br><br>METHODS: Prospective comparative study. SS-OCTA and SD-OCTA were used to scan the same eye with the modes of 3&#xd7;3 and 6&#xd7;6 mm[2] centered on the neovascularization. Only qualified images were chosen and the border of CNV was manually delineated by two graders independently. The area of CNV (ACNV), vascular perfusion density (PD), and vessel length density (VLD) within the delineation were calculated using Image J. The differences of CNV measurements between the two OCTA devices were compared using Bland-Altman analysis. The agreement between the two graders on the measurements of each device was compared using the intraclass correlation coefficient (ICC).<br><br>RESULTS: A total of 18 patients (22 eyes) with nAMD were included. The measurements of ACNV, PD, and VLD were 7.247&#xb1;4.586 and 4.901&#xb1;3.741 mm[2], 43.202&#xb1;9.636 and 34.904&#xb1;10.489, 6.339&#xb1;1.228 and 5.908&#xb1;1.741 mm[-1] for SS-OCTA and SD-OCTA, respectively. The differences between the two devices were 2.346&#xb1;3.030 mm[2] (Z=-3.782, P<0.0001), 8.298&#xb1;14.160 (Z=-2.419, P=0.016), and 0.431&#xb1;2.114 mm[-1] (Z=-0.828, P=0.408) for ACNV, PD and VLD, respectively. The ICC between two graders were 0.893 (P<0.001), 0.902 (P<0.001), 0.885 (P<0.001) for ACNV, PD, VLD in SS-OCTA, and 0.971 (P<0.001), 0.976 (P<0.001), 0.973 (P<0.001) in SD-OCTA, respectively.<br><br>CONCLUSION: Both OCTA devices have high imaging reliability. Compared with SD-OCTA, SS-OCTA has a larger ACNV measurements, but doesn't show better resolution of internal vessels of CNV and well signal strength.},
}
@article {pmid39559303,
year = {2024},
author = {Miao, JP and Zeng, YY and Gu, XM and Zhang, XY},
title = {Short-term fluctuation of intraocular pressure and influencing factors following intravitreal injection in patients with retinal vascular diseases.},
journal = {International journal of ophthalmology},
volume = {17},
number = {11},
pages = {2052-2059},
pmid = {39559303},
issn = {2222-3959},
abstract = {AIM: To investigate the patterns of short-term intraocular pressure (IOP) fluctuations and identify the contributing factors following intravitreal injection in patients with retinal vascular diseases.<br><br>METHODS: Totally 81 patients were enrolled in this case control study. Eyes were categorized into 7 groups, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), idiopathic choroidal neovascularization (CNV), proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), macular edema secondary to branch (BVOME) and central (CVOME) retinal vein occlusion. IOP was measured in all patients using rebound tonometer at 7 preset time points perioperatively. Additionally, based on the administered medication, the eyes were classified into three treatment groups, including dexamethasone intravitreal implant (IVO), intravitreal conbercept (IVC), and intravitreal ranibizumab (IVR). To compare IOP values at various time points across groups, we employed one-way ANOVA, independent sample t-test or &#x3c7; [2] test and multivariate logistic regression analysis.<br><br>RESULTS: Peak IOP values across all groups were observed at 40s, and 5min after intravitreal injection. Statistical differences in IOP were detected at the 5min among the 7 indication groups (F=2.50, P=0.029). When examing the impact of medications, the IVO group exhibited lower average IOP values at both 40s and 5min compared to the IVC and IVR groups (P<0.001; P=0.007). The IOP values at 40s and 5min were significantly higher in BVOME and CVOME group compared to non-retinal vein occlusion-secondary macular edema (RVOME) group (P<0.001). Multivariate logistic regression analysis further confirmed that IOP measurement at 40s was significantly higher in CVOME group than in non-RVOME group (OR=1.64, 95%CI: 1.09-2.47; P=0.018).<br><br>CONCLUSION: Needle size plays a crucial role in the transient changes of IOP following intravitreal injection. Before administering intravitreal injection to patients with central retinal vein occlusion, it is essential to exclude any underlysing causes of increased IOP.},
}
@article {pmid39558093,
year = {2025},
author = {Frank-Publig, S and Birner, K and Riedl, S and Reiter, GS and Schmidt-Erfurth, U},
title = {Artificial intelligence in assessing progression of age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {2},
pages = {262-273},
pmid = {39558093},
issn = {1476-5454},
mesh = {Humans ; *Artificial Intelligence ; Disease Progression ; *Macular Degeneration/diagnosis ; Algorithms ; Tomography, Optical Coherence/methods ; },
abstract = {The human population is steadily growing with increased life expectancy, impacting the prevalence of age-dependent diseases, including age-related macular degeneration (AMD). Health care systems are confronted with an increasing burden with rising patient numbers accompanied by ongoing developments of therapeutic approaches. Concurrent advances in imaging modalities provide eye care professionals with a large amount of data for each patient. Furthermore, with continuous progress in therapeutics, there is an unmet need for reliable structural and functional biomarkers in clinical trials and practice to optimize personalized patient care and evaluate individual responses to treatment. A fast and objective solution is Artificial intelligence (AI), which has revolutionized assessment of AMD in all disease stages. Reliable and validated AI-algorithms can aid to overcome the growing number of patients, visits and necessary treatments as well as maximize the benefits of multimodal imaging in clinical trials. Therefore, there are ongoing efforts to develop and validate automated algorithms to unlock more information from datasets allowing automated assessment of disease activity and disease progression. This review aims to present selected AI algorithms, their development, applications and challenges regarding assessment and prediction of AMD progression.},
}
@article {pmid39557279,
year = {2025},
author = {Wang, T and Song, Y and Bell, BA and Anderson, BD and Lee, TT and Yu, W and Dunaief, JL},
title = {Complement C3 knockout protects photoreceptors in the sodium iodate model.},
journal = {Experimental eye research},
volume = {250},
number = {},
pages = {110161},
pmid = {39557279},
issn = {1096-0007},
support = {S10 OD026860/OD/NIH HHS/United States ; T32 GM008076/GM/NIGMS NIH HHS/United States ; T32 EY007035/EY/NEI NIH HHS/United States ; R01 EY015240/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; R01 EY036292/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Iodates/toxicity ; Mice ; *Electroretinography ; *Complement C3/genetics/metabolism ; *Mice, Inbred C57BL ; *Mice, Knockout ; *Disease Models, Animal ; *Tomography, Optical Coherence ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Real-Time Polymerase Chain Reaction ; Enzyme-Linked Immunosorbent Assay ; Macular Degeneration/metabolism/genetics/prevention &amp; control ; Photoreceptor Cells, Vertebrate/metabolism/drug effects ; Immunohistochemistry ; },
abstract = {Complement factor 3 (C3) has emerged as a primary therapeutic target in age-related macular degeneration (AMD) supported by genetic, histologic, and clinical trial evidence. Yet, the site(s) of action are unclear. The purpose of this study was to test the effect of C3 knockout on photoreceptors and retinal pigment epithelial cells (RPE) in the sodium iodate (NaIO3) model, which mirrors some features of AMD. C3[-/-] and WT mice, both on a C57Bl/6J background, were injected intraperitoneally with 25 mg/kg NaIO3. Electroretinography and optical coherence tomography were performed 7 days later to assess retinal function and structure, respectively. Then, mice were euthanized for retinal immunohistochemistry, quantitative real-time PCR and enzyme-linked immunosorbent assays. NaIO3 increased C3 protein levels in the neural retina but not RPE. WT but not C3[-/-] mice showed NaIO3-induced iC3b deposition on photoreceptor outer segments. C3[-/-] mice were partially protected against photoreceptor layer thinning. There was partial preservation of rod and cone function in the C3[-/-] group. Neither RPE structure nor function was protected. These results suggest outer segment opsonization contributes to photoreceptor death in this model, and that targeting C3 can protect photoreceptor structure and function when RPE cells are stressed.},
}
@article {pmid39554957,
year = {2025},
author = {Kaufman, MW and DeParis, S and Oppezzo, M and Mah, C and Roche, M and Frehlich, L and Fredericson, M},
title = {Nutritional Supplements for Healthy Aging: A Critical Analysis Review.},
journal = {American journal of lifestyle medicine},
volume = {19},
number = {3},
pages = {346-360},
pmid = {39554957},
issn = {1559-8284},
abstract = {Background: Healthy aging is defined as survival to advanced age while retaining autonomy in activities of daily living, high societal participation, and good quality of life. Sarcopenia, insomnia, cognitive impairment, and changes in sensation can be key hinderances to healthy aging, but nutritional supplements may abate their impact. As research advances, an updated review on their efficacy on age-related conditions is warranted. Results: Sarcopenia can be mitigated through proper protein intake, supplements like creatine, and in certain situations Branched-Chain Amino Acids and Vitamin D, in adults over 65. Melatonin supplementation has moderate evidence for improving sleep, while valerian root lacks evidence. Magnesium, tart cherry, and kiwifruits have shown promising impacts on sleep in limited articles. Magnesium, Vitamin D, and B vitamin supplementation have been shown to improve cognition in those with mild cognitive impairment and Alzheimer's disease but require further study prior to recommendation. The Age-Related Eye Disease Study supplement combination is routinely recommended to reduce risk of progression to advance stages of age-related macular degeneration. Alpha-Lipoic Acid and Folate have been investigated for their roles in mitigating age-related hearing losses. Conclusions: Nutritional supplements and lifestyle changes may mitigate disabilities across multiple domains of age-related illnesses and promote healthy aging.},
}
@article {pmid39554634,
year = {2024},
author = {Ghiam, S and Pirouz, A and Adrean, SD},
title = {Potential New Phenotypic Presentation of Pentosan Polysulfate Sodium Maculopathy.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {6},
pages = {735-739},
pmid = {39554634},
issn = {2474-1272},
abstract = {Purpose: To describe a potential new phenotypic presentation of pentosan polysulfate sodium maculopathy. Methods: An observational case was analyzed. Results: A 55-year-old woman with interstitial cystitis who was treated with oral pentosan polysulfate sodium for 10 years presented with reports of decreased vision and metamorphopsia that had worsened over the past 3 months. On funduscopic examination, there were bilateral areas of retinal pigment epithelial hyperplasia inferior to the fovea with a surrounding halo of drusenoid material. Neurosensory retinal detachments with drusenoid deposition at the edges of the detachment were seen on spectral-domain optical coherence tomography. Conclusions: These findings could be mistaken for age-related macular degeneration, central serous retinopathy, Best disease, or adult vitelliform dystrophy. In this case, a review of pertinent medications assisted in making the diagnosis of toxic maculopathy. Proper diagnosis and prompt discontinuation of the inciting medication are necessary to avoid the risk for potentially irreversible retinal damage and vision loss.},
}
@article {pmid39554629,
year = {2024},
author = {Khodor, A and Choi, S and Nanda, T and Caranfa, JT and Ruiz-Lozano, RE and Desai, SH and Liang, M and Baumal, CR and Reed, DC and Cleary, TS and Heier, JS and Shah, CP and Witkin, AJ},
title = {Visual and Anatomic Responses in Patients With Neovascular Age-Related Macular Degeneration and a Suboptimal Response to Anti-VEGF Therapy Switched to Faricimab.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {6},
pages = {643-650},
pmid = {39554629},
issn = {2474-1272},
abstract = {Purpose: To determine the efficacy of switching to intravitreal (IVT) faricimab in patients with treatment-resistant neovascular age-related macular degeneration (nAMD) and determine the rates of reversion to the original antivascular endothelial growth factor (anti-VEGF) therapy. Methods: A retrospective chart review was performed of patients with nAMD and persistent fluid on optical coherence tomography previously treated with anti-VEGF injections who received at least 1 IVT faricimab injection between March 1, 2022, and January 31, 2023. Results: The study comprised 135 eyes of 119 patients. Before switching to IVT faricimab, the mean number of anti-VEGF injections in the previous 12 months was 10.7 ± 2.6 (SD) with a mean interval of 4.8 ± 1.3 weeks (range, 2-8). The mean follow-up was 11.6 ± 2 months. Thirty eyes (22.2%) switched to IVT faricimab returned to the original therapy. Of the 105 eyes remaining on IVT faricimab, 66 (62.9%) had no fluid at the last follow-up. Compared with the original treatment, there was a significant improvement in logMAR visual acuity at the last follow-up in eyes on IVT faricimab (0.42 vs 0.38; P < .01) and in central subfield thickness (286 µm vs 246 µm; P < .0001). There was also a significant increase in the dosing interval after the third injection vs before IVT faricimab was prescribed (4.8 weeks vs 5.5 weeks; P < .001). Conclusions: Faricimab has a potent drying effect and potential for increasing the injection interval in many eyes with nAMD and persistent fluid on other anti-VEGF agents. Although nearly 25% of eyes reverted to the original therapy because of an insufficient response or adverse events, the majority did not achieve fluid resolution after reversion.},
}
@article {pmid39554622,
year = {2024},
author = {Bloom, J and Madani, R and Haidar, AJ and Alasil, T},
title = {Faricimab Treatment of Polypoidal Choroidal Vasculopathy Resistant to Intravitreal Ranibizumab Injections and Ranibizumab Port Delivery (Susvimo).},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {6},
pages = {731-734},
pmid = {39554622},
issn = {2474-1272},
abstract = {Purpose: To report a case of polypoidal choroidal vasculopathy (PCV) recalcitrant to treatment with ranibizumab and with a ranibizumab port delivery system (Susvimo) but responsive to faricimab-svoa. Methods: A case and its findings were analyzed. Results: A 69-year-old Filipino man with PCV in the left eye was treated for 2 years with multiple ranibizumab intravitreal (IVT) injections followed by ranibizumab port delivery combined with rescue ranibizumab IVT injections, with no significant response clinically or on imaging. The visual acuity (VA) worsened to 20/100 OD. IVT treatment was switched to faricimab-svoa injections. After 2 injections, there was significant improvement on optical coherence tomography and in VA (20/60). Conclusions: This case shows the potential therapeutic benefits of targeting angiopoietin-2 in addition to vascular endothelial growth factor to treat PCV refractory to ranibizumab. Faricimab may provide an alternative to therapy with ranibizumab and verteporfin photodynamic therapy for the treatment of PCV.},
}
@article {pmid39553857,
year = {2024},
author = {Liu, Y and Tang, Z and Li, C and Zhang, Z and Zhang, Y and Wang, X and Wang, Z},
title = {AI-based 3D analysis of retinal vasculature associated with retinal diseases using OCT angiography.},
journal = {Biomedical optics express},
volume = {15},
number = {11},
pages = {6416-6432},
pmid = {39553857},
issn = {2156-7085},
abstract = {Retinal vasculature is the only vascular system in the human body that can be observed in a non-invasive manner, with a phenotype associated with a wide range of ocular, cerebral, and cardiovascular diseases. OCT and OCT angiography (OCTA) provide powerful imaging methods to visualize the three-dimensional morphological and functional information of the retina. In this study, based on OCT and OCTA multimodal inputs, a multitask convolutional neural network model was built to realize 3D segmentation of retinal blood vessels and disease classification for different retinal diseases, overcoming the limitations of existing methods that can only perform 2D analysis of OCTA. Two hundred thirty sets of OCT and OCTA data from 109 patients, including 138,000 cross-sectional images in normal and diseased eyes (age-related macular degeneration, retinal vein occlusion, and central serous chorioretinopathy), were collected from four commercial OCT systems for model training, validation, and testing. Experimental results verified that the proposed method was able to achieve a DICE coefficient of 0.956 for 3D segmentation of blood vessels and an accuracy of 91.49% for disease classification, and further enabled us to evaluate the 3D reconstruction of retinal vessels, explore the interlayer connections of superficial and deep vasculatures, and reveal the 3D quantitative vessel characteristics in different retinal diseases.},
}
@article {pmid39552594,
year = {2025},
author = {Delibay Akgun, Y and Kurt, E and Altinisik, M},
title = {Analysis of the Natural Course of Quiescent Macular Neovascularization with Optical Coherence Tomography Angiography.},
journal = {European journal of ophthalmology},
volume = {35},
number = {3},
pages = {1075-1081},
doi = {10.1177/11206721241298025},
pmid = {39552594},
issn = {1724-6016},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; *Fluorescein Angiography/methods ; Male ; Aged ; Visual Acuity/physiology ; Follow-Up Studies ; Disease Progression ; Middle Aged ; Fundus Oculi ; Retrospective Studies ; *Macula Lutea/pathology ; *Retinal Neovascularization/physiopathology/diagnosis ; Aged, 80 and over ; *Choroidal Neovascularization/physiopathology/diagnosis ; },
abstract = {PurposeThis study investigates the natural progression of quiescent macular neovascularization (qMNV) using optical coherence tomography angiography (OCTA).MethodsThe study monitored 30 eyes of 28 qMNV patients over a period of at least six months. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and OCTA were used to perform qualitative and quantitative analyses, noting any cases of activation during follow-up.ResultsAmong the 30 eyes (14 female, mean age 69.70 ± 7.63 years), 21 had age-related macular degeneration (AMD) and 9 had pachychoroid neovasculopathy (PNV). The mean follow-up duration was 18.9 months. There were no significant changes in qualitative morphological features, BCVA, or choroidal thickness (p > 0.05). However, there was a statistically significant increase in the areas of MNV and flow (p = 0.043 and p = 0.018, respectively). BCVA and MNV area showed no significant correlation (p = 0.103). Four cases (13.33%) showed activation after an average follow-up period of 27.75 months (6 to 48). Additionally, extrafoveal location was identified as a significant risk factor for exudation (p = 0.033).ConclusionOCTA is a valuable tool for monitoring qMNV and identifying potential predictors of disease activation. The qMNV area may increase over time, even in the absence of activation. Extrafoveal location appears to be a potential risk factor for qMNV activation.},
}
@article {pmid39551480,
year = {2025},
author = {Ballester Dolz, P and Ålander, K and Smedberg, P and Vihlborg, P and Bryngelsson, IL and Westerlund, J and Makdoumi, K},
title = {Eye diseases in chronic kidney disease: A nationwide longitudinal case-control study in Sweden.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {2},
pages = {209-217},
pmid = {39551480},
issn = {1442-9071},
mesh = {Humans ; Sweden/epidemiology ; Male ; Female ; *Renal Insufficiency, Chronic/epidemiology/complications ; Retrospective Studies ; Case-Control Studies ; Middle Aged ; Incidence ; Aged ; *Eye Diseases/epidemiology/etiology ; Adult ; Risk Factors ; Aged, 80 and over ; Longitudinal Studies ; Young Adult ; },
abstract = {BACKGROUND: Chronic kidney disease (CKD) is a growing health issue that is becoming more prevalent globally, increasing financial cost on healthcare systems. The purpose of this study is to investigate the incidence of eye diseases in patients diagnosed with CKD in Sweden and to evaluate which eye diseases are most likely to develop.<br><br>METHODS: A longitudinal population-based retrospective case-control study was conducted including all individuals diagnosed with chronic kidney disease during the time period 2001-2019. A total of 19&#x2009;455 cases and 38&#x2009;890 controls were included. For each case, two controls were matched with the same sex, age, and county of residence.<br><br>RESULTS: CKD patients had a significantly higher risk of contracting any eye disease compared to individuals without kidney disease HR 1.73 (CI 1.67-1.79), with an elevated risk for all blocks of diagnoses except for glaucoma HR 0.95 (CI 0.85-1.06). However, this condition developed earlier in cases than in controls. Subanalyses showed an increased risk for chronic eye disease patients to develop cataract HR 1.70 (CI 1.63-1.78), other retinal disorders HR 1.86 (CI 1.72-2.02), and retinal vascular occlusions HR 2.08 (CI 1.73-2.51). In general, diagnosis of an eye disease occurred earlier in cases than controls.<br><br>CONCLUSIONS: The results from this study suggest that CKD patients have an increased risk to develop eye disease. Ocular disease seems to develop considerably earlier in CKD, even without staging the severity of the disease, with particularly high risk of developing retinal diseases and cataracts. Screening for eye disease in CKD should be considered.},
}
@article {pmid39551387,
year = {2025},
author = {Wang, J and Nnoromele, PO and Liu, YV and Johnston, RJ and Singh, MS},
title = {Cellular component transfer between photoreceptor cells of the retina.},
journal = {Progress in retinal and eye research},
volume = {104},
number = {},
pages = {101317},
pmid = {39551387},
issn = {1873-1635},
support = {R01 EY030872/EY/NEI NIH HHS/United States ; R01 EY033103/EY/NEI NIH HHS/United States ; T32 GM136577/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Photoreceptor Cells, Vertebrate/cytology/physiology/transplantation ; Retinal Degeneration/physiopathology ; },
abstract = {Photoreceptor transplantation is a potential therapeutic strategy for degenerative retinal diseases. Studies on mechanisms contributing to retinal regeneration and vision repair identified cellular components transfer (CCT) as playing a role, in addition to somatic augmentation (referred to as "cell replacement" in this paper). In CCT, donor photoreceptors shuttle proteins, RNA, and mitochondria to host photoreceptors through intercellular connections. The discovery of CCT in the transplantation context triggered a re-interpretation of prior transplantation studies that generally did not include specific CCT assays and thereby broadly emphasized the cell replacement model, reflecting the prevailing understanding of retinal transplantation biology at that time. In addition to clarifying our understanding of photoreceptor biology, CCT has raised the possibility of developing treatments to replenish molecular deficiencies in diseased photoreceptor cells. As the CCT field evolves, investigators have used diverse terminology, and implemented different CCT assays following transplantation in animal models. The non-standardized terminology of CCT and absent minimal assay standards for detection can hinder communication between investigators and comparison between studies. In this review, we discuss the current understanding of CCT, provide an overview of transplantation and regeneration studies in small and large animals, and propose terminology and a minimal assay standard for CCT. Further research on CCT may eventually provide new avenues to treat a range of hereditary and acquired retinopathies while illuminating mechanisms of cell-cell interaction in the retina.},
}
@article {pmid39549494,
year = {2025},
author = {Xiao, Y and Shao, Y and Chen, Z and Zhang, R and Ding, X and Zhao, J and Liu, S and Fukuyama, T and Zhao, Y and Peng, X and Tian, G and Wen, S and Zhou, X},
title = {MIU-Net: Advanced multi-scale feature extraction and imbalance mitigation for optic disc segmentation.},
journal = {Neural networks : the official journal of the International Neural Network Society},
volume = {182},
number = {},
pages = {106895},
doi = {10.1016/j.neunet.2024.106895},
pmid = {39549494},
issn = {1879-2782},
mesh = {*Optic Disk/diagnostic imaging ; Humans ; *Neural Networks, Computer ; Algorithms ; Myopia, Degenerative ; Image Processing, Computer-Assisted/methods ; },
abstract = {Pathological myopia is a severe eye condition that can cause serious complications like retinal detachment and macular degeneration, posing a threat to vision. Optic disc segmentation helps measure changes in the optic disc and observe the surrounding retina, aiding early detection of pathological myopia. However, these changes make segmentation difficult, resulting in accuracy levels that are not suitable for clinical use. To address this, we propose a new model called MIU-Net, which improves segmentation performance through several innovations. First, we introduce a multi-scale feature extraction (MFE) module to capture features at different scales, helping the model better identify optic disc boundaries in complex images. Second, we design a dual attention module that combines channel and spatial attention to focus on important features and improve feature use. To tackle the imbalance between optic disc and background pixels, we use focal loss to enhance the model's ability to detect minority optic disc pixels. We also apply data augmentation techniques to increase data diversity and address the lack of training data. Our model was tested on the iChallenge-PM and iChallenge-AMD datasets, showing clear improvements in accuracy and robustness compared to existing methods. The experimental results demonstrate the effectiveness and potential of our model in diagnosing pathological myopia and other medical image processing tasks.},
}
@article {pmid39548881,
year = {2025},
author = {Arnold-Vangsted, A and Schou, MG and Balaratnasingam, C and Cehofski, LJ and Chhablani, J and van Dijk, EHC and Eriksen, NS and Grauslund, J and Hajari, JN and Sabaner, MC and Schneider, M and Subhi, Y},
title = {Efficacy of intravitreal faricimab therapy for polypoidal choroidal vasculopathy: A systematic review and meta-analysis.},
journal = {Acta ophthalmologica},
volume = {103},
number = {3},
pages = {247-256},
doi = {10.1111/aos.16797},
pmid = {39548881},
issn = {1755-3768},
mesh = {Humans ; Angiogenesis Inhibitors/administration &amp; dosage ; *Choroid/blood supply ; *Choroidal Neovascularization/drug therapy/diagnosis ; Fluorescein Angiography ; Fundus Oculi ; Intravitreal Injections ; Polypoidal Choroidal Vasculopathy ; *Polyps/drug therapy/diagnosis ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; },
abstract = {Polypoidal choroidal vasculopathy (PCV) is an aneurismal type of macular neovascularization that show similarities with age-related macular degeneration and diseases that are part of the pachychoroid disease spectrum. Exudative changes in PCV can be treated with intravitreal anti-vascular endothelial growth factor monotherapy; however, a combination therapy with photodynamic therapy may be required. In this systematic review and meta-analysis, we evaluated the efficacy of faricimab for PCV. We searched 12 literature databases for eligible studies. All study evaluation and data extraction were made by two authors in duplicate. Studies eligible for analysis were included for a qualitative and quantitative review. We identified seven studies with data from 150 eyes with PCV, five studies were of treatment-naïve eyes who were commenced in faricimab monotherapy, and two studies were of switch-over to faricimab from other anti-VEGF drugs. After faricimab loading dose in treatment-naïve eyes, the best-corrected visual acuity (BCVA) remained stable at -0.09 (95% CI: -0.20-0.03) logMAR, central retinal thickness (CRT) decreased -169 (95% CI: -311--27) μm, and 48.7 (95% CI: 32.5-65.0) % of eyes obtained polyp closure. In switch-over eyes, 57%-67% experienced fluid reduction and 21% were able to extend their treatment interval. In conclusion, faricimab monotherapy for PCV leads to acceptable clinical outcomes in terms of stable BCVA, reduction of CRT, and high incidence of polyp closure. Some cases may benefit from a switch to faricimab. However, long-term efficacy studies and controlled comparative studies are warranted.},
}
@article {pmid39548212,
year = {2024},
author = {Han, JM and Han, J and Ko, J and Jung, J and Park, JI and Hwang, JS and Yoon, J and Jung, JH and Hwang, DD},
title = {Anti-VEGF treatment outcome prediction based on optical coherence tomography images in neovascular age-related macular degeneration using a deep neural network.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {28253},
pmid = {39548212},
issn = {2045-2322},
support = {2023R1A2C2007625//National Research Foundation of Korea/ ; NRF-2022R1F1A1074063//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Female ; Aged ; *Neural Networks, Computer ; Treatment Outcome ; *Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use ; Macular Degeneration/drug therapy/diagnostic imaging ; Aged, 80 and over ; Middle Aged ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the number of affected patients is increasing worldwide. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard therapy for neovascular AMD (nAMD), and optical coherence tomography (OCT) is a crucial tool for evaluating the anatomical condition of the macula. However, OCT has limitations in accurately predicting the degree of functional and morphological improvement following intravitreal injections. Artificial intelligence (AI) has been proposed as a tool for predicting the treatment response of nAMD based on OCT biomarkers. Our study focuses on the development and assessment of an AI model utilizing the DenseNet201 algorithm. The model aims to predict anatomical improvement based on OCT images before, and during anti-VEGF therapy. The training process involves two scenarios: (1) using only preinjection OCT images and (2) utilizing both OCT images before and during anti-VEGF therapy for model training. The outcomes of our investigation, involving 2068 images from a cohort of 517 Korean patients diagnosed with nAMD, indicate that the AI model we introduced surpassed the predictive performance of ophthalmologists. The model exhibited a sensitivity of 0.915, specificity of 0.426, and accuracy of 0.820. Notably, its predictive capabilities were further enhanced with the inclusion of additional OCT images taken after the first and second injections during the loading phase. The treatment prediction performance of the model was the highest when using all input modalities (before injection, and after the first and second injections) and concatenation-based fusion layers. This study highlights the potential of AI in assisting individualized and tailored nAMD treatment.},
}
@article {pmid39548108,
year = {2024},
author = {Birner, K and Reiter, GS and Steiner, I and Deák, G and Mohamed, H and Schürer-Waldheim, S and Gumpinger, M and Bogunović, H and Schmidt-Erfurth, U},
title = {Topographic and quantitative correlation of structure and function using deep learning in subclinical biomarkers of intermediate age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {28165},
pmid = {39548108},
issn = {2045-2322},
mesh = {Humans ; *Deep Learning ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/pathology/diagnostic imaging/physiopathology ; Female ; Male ; Aged ; *Biomarkers ; Retinal Drusen/diagnostic imaging/physiopathology/pathology ; Aged, 80 and over ; Middle Aged ; Visual Field Tests ; },
abstract = {To examine the morphological impact of deep learning (DL)-quantified biomarkers on point-wise sensitivity (PWS) using microperimetry (MP) and optical coherence tomography (OCT) in intermediate AMD (iAMD). Patients with iAMD were examined by OCT (Spectralis). DL-based algorithms quantified ellipsoid zone (EZ)-thickness, hyperreflective foci (HRF) and drusen volume. Outer nuclear layer (ONL)-thickness and subretinal drusenoid deposits (SDD) were quantified by human experts. All patients completed four MP examinations using an identical custom 45 stimuli grid on MP-3 (NIDEK) and MAIA (CenterVue). MP stimuli were co-registered with corresponding OCT using image registration algorithms. Multivariable mixed-effect models were calculated. 3.600 PWS from 20 eyes of 20 patients were analyzed. Decreased EZ thickness, decreased ONL thickness, increased HRF and increased drusen volume had a significant negative effect on PWS (all p < 0.001) with significant interaction with eccentricity (p < 0.001). Mean PWS was 26.25 ± 3.43 dB on MP3 and 22.63 ± 3.69 dB on MAIA. Univariate analyses revealed a negative association of PWS and SDD (p < 0.001). Subclinical changes in EZ integrity, HRF and drusen volume are quantifiable structural biomarkers associated with reduced retinal function. Topographic co-registration between structure on OCT volumes and sensitivity in MP broadens the understanding of pathognomonic biomarkers with potential for evaluation of quantifiable functional endpoints.},
}
@article {pmid39547643,
year = {2025},
author = {Rijken, R and Pameijer, EM and Gerritsen, B and Hiddingh, S and Stehouwer, M and de Boer, JH and Imhof, SM and van Leeuwen, R and Kuiper, JJ},
title = {Blood integrin- and cytokine-producing T cells are associated with stage and genetic risk score in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {250},
number = {},
pages = {110154},
doi = {10.1016/j.exer.2024.110154},
pmid = {39547643},
issn = {1096-0007},
mesh = {Humans ; Male ; Female ; Aged ; *Cytokines/metabolism/genetics ; Tomography, Optical Coherence ; Flow Cytometry ; Macular Degeneration/genetics/blood/metabolism ; Aged, 80 and over ; Risk Factors ; Genetic Predisposition to Disease ; Genetic Risk Score ; },
abstract = {Age-related macular degeneration (AMD) remains a leading cause of vision loss in the geriatric population. There are age-related changes in peripheral blood leukocyte composition, but their significance for AMD remains unclear. We aimed to determine changes in immune cell populations in the blood of AMD patients. A standardized 31-parameter flow cytometry analysis was conducted on peripheral blood mononuclear cells from 59 patients with early and advanced AMD and 39 controls without AMD, all older than 65 years. Fundus photography and optical coherence tomography were used to classify disease stages and a custom genotype array was used to compute an AMD genetic risk score based on 52 AMD disease risk variants (GRS-52). A generalized linear regression model corrected for age, sex, and smoking status revealed that AMD patients showed decreased frequencies of CD4[+] T helper cell population expressing Integrin Alpha E (CD103) (Padj = 0.019). We further noted that early AMD was characterized by increased interleukin-4 (IL-4)-producing CD4[+] T helper cells (Padj = 0.013; <0.001), as well as IL-4-producing cytotoxic CD8[+] T cells (Padj = 0.016; <0.001). Reclassification of samples based on the GRS-52 revealed that IL-17-producing T cells decreased incrementally across GRS-52 categories. In AMD, alterations in peripheral blood leukocyte populations are associated with genetic risk score and disease stage and include specifically IL-4 and IL-17A cytokine-producing and CD103 integrin-expressing T cell populations.},
}
@article {pmid39547357,
year = {2025},
author = {Duic, C and Vance, E and Agrón, E and Keenan, TDL and , },
title = {Alcohol Consumption and Risk of Age-Related Macular Degeneration and Geographic Atrophy Progression: Age-Related Eye Diseases Study 2 Report 34.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {3},
pages = {200-211},
pmid = {39547357},
issn = {2468-6530},
support = {Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; ZIA EY000485/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Disease Progression ; *Geographic Atrophy/diagnosis/etiology/epidemiology ; *Alcohol Drinking/adverse effects/epidemiology ; Aged ; Follow-Up Studies ; Risk Factors ; *Macular Degeneration/diagnosis/etiology/epidemiology ; Middle Aged ; Prospective Studies ; Aged, 80 and over ; Fundus Oculi ; Incidence ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Risk Assessment/methods ; },
abstract = {PURPOSE: To examine potential relationships between alcohol consumption and age-related macular degeneration (AMD) progression, including progression to late AMD and geographic atrophy (GA) enlargement rate.<br><br>DESIGN: Post hoc analysis of cohorts within the Age-Related Eye Diseases Study&#xa0;2.<br><br>PARTICIPANTS: A total of 6670 eyes (of 3673 participants) with no late AMD at baseline; 1143 eyes (of 841 participants) with GA at &#x2265;2 consecutive visits.<br><br>METHODS: Color fundus photographs were collected at annual study visits and graded centrally for late AMD, GA area, and GA proximity. Alcohol consumption was calculated by food frequency questionnaire. Regression analyses of disease progression were performed according to alcohol consumption.<br><br>MAIN OUTCOME MEASURES: Progression to late AMD and its subtypes; GA area-based progression; GA proximity-based progression.<br><br>RESULTS: Over a mean follow-up of 4.5 years, 40.2% of eyes progressed to late AMD. In men, with alcohol tertile 1 (no regular consumption) as reference, hazard ratios for progression to late AMD were 0.69 (95% confidence interval [CI], 0.55-0.87; P&#xa0;= 0.0015) for tertile 2 and 0.85 (0.71-1.02; P&#xa0;= 0.079) for tertile 3. In women, hazard ratios were 1.12 (0.95-1.31, P&#xa0;= 0.17) and 0.85 (0.72-1.00, P&#xa0;= 0.046), respectively. Over a mean follow-up of 3.1 years, GA area-based progression was significantly faster in women than men, at 0.295 (95% CI, 0.278-0.311) and 0.260 mm/year (95% CI,&#xa0;0.241-0.279), respectively (P&#xa0;= 0.007). In men, area-based progression differed significantly by alcohol tertile (P&#xa0;= 0.0001), at 0.275 (95% CI,&#xa0;0.248-0.303), 0.183 (95% CI,&#xa0;0.143-0.223), and 0.280 mm/year (0.254-0.306) in tertiles 1 to 3, respectively. In women, the area-based rate did not differ significantly by alcohol tertile (P&#xa0;= 0.11). In men only, Centers for Disease Control and Prevention-defined heavy drinking was associated with faster progression (P&#xa0;= 0.024), at 0.306 (95% CI,&#xa0;0.262-0.349) versus 0.252 mm/year (95% CI,&#xa0;0.233-0.270). In 808 eyes with noncentral GA, GA proximity-based progression did not differ significantly by alcohol tertile (P&#xa0;= 0.55).<br><br>CONCLUSIONS: Moderate alcohol consumption is associated with decreased risk of progression to late AMD in men. Geographic atrophy progression is faster in women, but its relationship with alcohol consumption is much stronger in men. In men, moderate consumption is associated with slower GA progression and higher consumption with faster progression. Although some of these associations may also relate to confounding, they might suggest that individuals with GA should avoid high alcohol consumption.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39544716,
year = {2024},
author = {Zhang, X and Zhao, X and Xin, X},
title = {PCSK7, a potential target for the treatment of age-related macular degeneration: inhibition of retinal epithelial cell death.},
journal = {International journal of clinical and experimental pathology},
volume = {17},
number = {10},
pages = {371-380},
pmid = {39544716},
issn = {1936-2625},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a complex disease with a pathophysiology that remains incompletely understood. PCSK7 is closely related to the normal development of ocular tissues; however, the roles and mechanisms of PCSK7 in AMD have yet to be elucidated. Therefore, the purpose of this study was to investigate the specific manifestations of PCSK7 in AMD.<br><br>METHODS: An AMD cell model was established by using hydrogen peroxide (H2O2)-treated ARPE-19 cells. The efficiency of PCSK7 overexpression was analyzed by western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR). Subsequently, a Cell Counting Kit 8 (CCK-8) assay was employed to assess the proliferation of ARPE-19 cells, while flow cytometry and immunofluorescence were utilized to examine apoptosis. Iron accumulation and glutathione (GSH) levels in cells were measured using Enzyme-linked immunosorbent assay (ELISA), and WB was conducted to evaluate the expression of anti-ferroptosis protein. Finally, JC-1 staining was performed to assess mitochondrial membrane potential.<br><br>RESULTS: Overexpressing of PCSK7 enhanced the proliferation and inhibited the apoptosis of ARPE-19 cells treated with H2O2. Additionally, increased PCSK7 expression suppressed intracellular iron levels and GSH content, thereby inhibiting the ferroptosis process. Furthermore, overexpression of PCSK7 restored mitochondrial membrane potential, alleviating H2O2-induced mitochondrial damage.<br><br>CONCLUSIONS: PCSK7 might be one of the targets for the treatment of AMD through the regulation of retinal epithelial cell death.},
}
@article {pmid39544140,
year = {2025},
author = {Sen, S and de Guimaraes, TAC and Filho, AG and Fabozzi, L and Pearson, RA and Michaelides, M},
title = {Stem cell-based therapies for retinal diseases: focus on clinical trials and future prospects.},
journal = {Ophthalmic genetics},
volume = {46},
number = {4},
pages = {324-337},
doi = {10.1080/13816810.2024.2423784},
pmid = {39544140},
issn = {1744-5094},
mesh = {Humans ; *Stem Cell Transplantation/methods/trends ; Clinical Trials as Topic ; *Retinal Diseases/therapy ; Animals ; },
abstract = {Stem cell-based therapy has gained importance over the past decades due to huge advances in science and technology behind the generation and directed differentiation of pluripotent cells from embryos and adult cells. Preclinical proof-of-concept studies have been followed by clinical trials showing efficacy and safety of transplantation of stem cell-based therapy, which are beginning to establish this as a modality of treatment. Disease candidates of interest are primarily conditions that may benefit from replacing dead or dying cells, including advanced inherited retinal dystrophies and age-related macular degeneration, and predominantly seek to transplant either RPE or photoreceptors, although neurotrophic approaches have also been trialed. Whilst a consensus has yet to be reached about the best stage/type of cells for transplantation (stem cells, progenitor cells, differentiated RPE and photoreceptors) and the methods of implantation (sheet, suspension), several CTs have shown safety. There remain potential concerns regarding tumorigenicity and immune rejection; however, with ongoing improvements in cell generation, selection, and delivery, these can be minimized. Earlier studies showed efficacy with immunosuppressive drugs to prevent rejection, and recent donor-matched transplants have avoided the need for immunosuppression. Retinal regenerative medicine is a challenging field and is in a nascent stage but holds tremendous promise. This narrative review delves into the current understanding of stem cells and the latest clinical trials of retinal cell transplantation.},
}
@article {pmid39544046,
year = {2025},
author = {Beretta, F and Zucchiatti, I and Sacconi, R and Bandello, F and Querques, G},
title = {Multiwavelength photobiomodulation in atrophic age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {35},
number = {4},
pages = {1336-1341},
doi = {10.1177/11206721241298316},
pmid = {39544046},
issn = {1724-6016},
mesh = {Humans ; Visual Acuity/physiology ; Male ; Retrospective Studies ; Female ; Aged ; Fluorescein Angiography/methods ; *Low-Level Light Therapy/methods ; Tomography, Optical Coherence/methods ; *Geographic Atrophy/radiotherapy/diagnosis/physiopathology ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; },
abstract = {PurposeTo evaluate photobiomodulation (PBM) safety and efficacy in patient with atrophic AMD and to explore tissue effects using Spectrally Resolved Autofluorescence (SrAF) to identify a potential biomarker indicative of mitochondrial activity, the primary PBM target.MethodsThis retrospective, non-comparative case series involved six eyes of five patients with atrophic AMD, conducted at the Medical Retina and Imaging Unit, IRCCS San Raffaele Hospital in Milan, Italy. At baseline and follow-ups (after one and three months) a complete ophthalmological assessment and multimodal imaging, including spectrally resolved autofluorescence (SrAF), were performed. PBM treatment (Valeda Light Delivery System - LumiThera) was administered in nine sessions over three weeks. The SrAF images were analyzed to evaluate the effect of the treatment.ResultsSix eyes of five patients with atrophic AMD received PBM at baseline. Best corrected visual acuity (BCVA), mean central macular thickness (CMT), mean retinal sensitivity on microperimetry and the atrophic area have remained stable. No eyes developed foveal atrophy after the treatment. The image analysis in SrAF showed an increase in the highlighted area of 4.89% after one month and 17.11% after three months. No adverse systemic or local side effects were reported.ConclusionPBM is a safe treatment for the human retina. The evaluation of the retinal area within the green light spectrum (575 nm) in SrAF is a potential indirect biomarker of mitochondrial activity and could be used to assess treatment efficacy in clinical studies.},
}
@article {pmid39542710,
year = {2025},
author = {Hashimoto, Y and Hunt, AR and Wells, JM and Banerjee, G and Ferrier, R and Barry, R and Field, A and Game, J and Hooper, CY and Barthelmes, D and Gillies, MC},
title = {Outlier ophthalmologists in the treatment of neovascular age-related macular degeneration with intravitreal therapy.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {5},
pages = {606-613},
pmid = {39542710},
issn = {1468-2079},
mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Male ; Aged, 80 and over ; *Visual Acuity ; Female ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Ophthalmologists/standards ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Prospective Studies ; *Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; Choroidal Neovascularization/drug therapy ; Follow-Up Studies ; Databases, Factual ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: To compare individual ophthalmologists grouped as outliers or non-outliers based on the mean 12-month visual acuity (VA) outcomes for their patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospectively designed database study included treatment-na&#xef;ve eyes with nAMD starting vascular endothelial growth factor inhibitors between July 2018 and April 2023 in Australia. Ophthalmologists were classified into high outliers, non-outliers and low outliers with a funnel plot of the adjusted mean 12-month VA change. The number of injections, last injection interval and proportion of visits where choroidal neovascularisation was active were compared between the groups.<br><br>RESULTS: 38 ophthalmologists who treated a total of 1266 eyes (male, 35%; mean age, 81 years old) were classified into 1 high outlier, 34 non-outliers and 3 low outliers (mean VA change, 7.5, 5.1 and 2.5 letters, respectively). The high outlier gave significantly more injections than the non-outliers (mean, 8.6 vs 7.7; p<0.001), while the low outliers administered significantly fewer injections than the non-outliers (mean, 7.1 vs 7.7; p=0.009). The last injection interval was shortest in the high outlier's eyes (9.4 weeks), followed by non-outliers' (10.8 weeks; p=0.04 (vs high outlier's)) and low outliers' (11.8 weeks; p=0.22 (vs non-outliers')). The low outliers' patients had more visits with intraretinal fluid (59%) than non-outliers' (29%; p<0.001) and high outlier's patients (31%; p<0.001).<br><br>CONCLUSION: The low outliers' eyes had fewer injections, a longer treatment interval and more visits with intraretinal fluid. Building a system through which low outliers are anonymously notified of their performance would help improve general quality of care.},
}
@article {pmid39540601,
year = {2025},
author = {Mares, V and Reiter, GS and Gumpinger, M and Leigang, O and Bogunovic, H and Barthelmes, D and Nehemy, MB and Schmidt-Erfurth, U},
title = {Correlation of retinal fluid and photoreceptor and RPE loss in neovascular AMD by automated quantification, a real-world FRB! analysis.},
journal = {Acta ophthalmologica},
volume = {103},
number = {3},
pages = {295-303},
pmid = {39540601},
issn = {1755-3768},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Subretinal Fluid/diagnostic imaging ; Male ; Female ; *Wet Macular Degeneration/diagnosis/drug therapy ; Aged ; *Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Fluorescein Angiography/methods ; *Photoreceptor Cells, Vertebrate/pathology ; Intravitreal Injections ; Aged, 80 and over ; Registries ; Retrospective Studies ; Middle Aged ; Fundus Oculi ; Algorithms ; },
abstract = {PURPOSE: To quantify ellipsoid zone (EZ) loss during anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) and correlate these findings with nAMD disease activity using artificial intelligence-based algorithms.<br><br>METHODS: Spectral domain optical coherence tomography (Spectralis, Heidelberg Engineering) images from nAMD treatment-na&#xef;ve patients from the Fight Retinal Blindness! (FRB!) Registry from Z&#xfc;rich, Switzerland were processed at baseline and over 3&#x2009;years of follow-up. An approved deep learning algorithm (Fluid Monitor, RetInSight) was used to automatically quantify intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED). An ensemble U-net deep learning algorithm was used to automated quantify EZ integrity based on EZ layer thickness. The impact of fluid volumes on EZ thickness and late-stages outcomes were calculated using Wilcoxon rank-sum tests, a linear mixed model and a longitudinal panel regression model.<br><br>RESULTS: Two hundred and eleven eyes from 158 patients were included. The mean&#x2009;&#xb1;&#x2009;SD EZ loss area in the central 6&#x2009;mm was 1.81&#x2009;&#xb1;&#x2009;2.68&#x2009;mm[2] at baseline and reached 6.21&#x2009;&#xb1;&#x2009;6.15&#x2009;mm[2] at month 36. Higher fluid volumes (top 25%) of IRF and PED in the central 1 and 6&#x2009;mm of the macula were significantly associated with more advanced EZ thinning and loss compared to the low fluid volume subgroup. The high SRF subgroup in the linear regression model showed no statistically significant association with EZ integrity in the central macula; however, the longitudinal analysis revealed an increased EZ thickness with no additional loss.<br><br>CONCLUSIONS: Intraretinal fluid and PED volumes and their resolution pattern have an impact on alteration of the underlying EZ layer. AI-supported quantifications are helpful in quantifying early signs of macular atrophy and providing individual risk profiles as a basis for tailored therapies for optimized visual outcomes.},
}
@article {pmid39539883,
year = {2024},
author = {Wolek, M and Wollocko, B and Li, DM and Bansal, J and Ghani, N and Mackey, M and Chaudhary, K},
title = {Adjusting for Glycemic Control in Assessing the Relationship Between Age-Related Macular Degeneration and Diabetic Retinopathy.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71479},
pmid = {39539883},
issn = {2168-8184},
abstract = {Purpose Studies regarding the relationship between age-related macular degeneration (AMD) and diabetic retinopathy (DR) conflict: while some support that AMD is protective against DR, others find the opposite. The mechanism by which AMD may protect against DR is unclear. We sought to assess the association between AMD and DR when controlling for glycemic control in patients with diabetes mellitus (DM) type II. Methods We identified 461 unique patients over 55 years old with a diagnosis of DM type II seen in our academic retina clinic in Stony Brook, New York between 12/31/2019 and 12/31/2020. Data were manually extracted and the population was split based on the presence of AMD diagnosis. Multivariate regression analyses were then performed comparing the prevalence of DR between groups while controlling for A1c. Secondary endpoints included demographic differences and smoking status. Results Among the 461 patients, 118 (25.6%) had a diagnosis of AMD. Compared to patients without AMD, patients with AMD were older (69 vs. 66; OR 1.05; p=0.005) and less likely to have DR (37.3% vs. 59.2%; OR 0.35; p<0.001). There was no difference in average A1c between groups. Conclusion This is the first reported study assessing the relationship between AMD and DR while controlling for A1c. In our population, diagnosis of AMD was associated with significantly reduced odds of having DR. As AMD and DR appear to be related even after holding A1c constant, researchers should use caution when using DR as a surrogate for diabetic control in the context of AMD.},
}
@article {pmid39539849,
year = {2025},
author = {Ahmed, I and Wu, DM},
title = {Drusen Disappearance After Retinal Detachment Repair.},
journal = {Journal of vitreoretinal diseases},
volume = {9},
number = {1},
pages = {109-112},
pmid = {39539849},
issn = {2474-1272},
abstract = {Purpose: To describe a case of a drusenoid pigment epithelial detachment that resolved after retinal detachment (RD) repair using multimodal imaging. Methods: A single case was evaluated. Results: An 83-year-old woman with intermediate age-related macular degeneration had repair of a rhegmatogenous RD with subsequent resolution of macular drusen and improved visual acuity and metamorphopsia. Conclusions: RD repair may be associated with resolution of drusen, leading to improved functional outcomes.},
}
@article {pmid39539835,
year = {2025},
author = {Bloemhof, CMP and Lim, MJ and Hwang, JC},
title = {Changes in Internet Search Behavior After a Direct-to-Consumer Advertising Campaign for Faricimab-svoa.},
journal = {Journal of vitreoretinal diseases},
volume = {9},
number = {1},
pages = {54-58},
pmid = {39539835},
issn = {2474-1272},
abstract = {Purpose: To analyze changes in Google search volume after US Food and Drug Administration (FDA) approval and initiation of a direct-to-consumer marketing campaign for faricimab-svoa. Methods: Google Trends data between December 26, 2021, and June 17, 2023, were downloaded and searched for terms prominently featured in the marketing campaign, including "wet AMD", "diabetic macular edema", "Vabysmo", and "faricimab-svoa". Data were standardized to the week and the term with the highest search volume, resulting in weekly relative search volumes for each term. The mean relative search volume and percentage change in relative search volume were calculated for the time periods of interest. Results: The direct-to-consumer campaign was associated with an increase in relative search volume in the first month for the terms "Vabysmo" (2.5% to 18.0%) and "wet AMD" (3.0% to 77.3%) and was sustained in the second month (P < .01). No significant changes in relative search volume were seen for the terms "diabetic macular edema" or "faricimab-svoa". After FDA approval, "Vabysmo" had the only significant increase in relative search volume (0.3% to 2.8%; P = .02). Conclusions: A direct-to-consumer advertising campaign for faricimab-svoa was associated with a surge in Google search volume of 620% and 2475% for "Vabysmo" and "wet AMD," respectively (P < .01), without a corresponding increase for "diabetic macular edema". Although FDA approval was associated with an increase in search volume for "Vabysmo" (P = .02), the marketing campaign was more influential at driving internet search behavior.},
}
@article {pmid39539820,
year = {2024},
author = {Staurenghi, G and Souied, EH and Iida, T and Chow, DR and Wolf, A and Gallego-Pinazo, R and Viola, F and Kaiser, PK},
title = {Imaging-Guided Classification of Neovascularization in Neovascular Age-Related Macular Degeneration: Progress to Date.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {6},
pages = {709-718},
pmid = {39539820},
issn = {2474-1272},
abstract = {Purpose: To review the evolution of terminology describing the classification of lesions in neovascular age-related macular degeneration (nAMD) based on retinal imaging technologies. Methods: A review of the current and historical literature on imaging-guided classification of neovascularization in nAMD was performed. Results: Imaging-guided classification of neovascularization in nAMD facilitates an understanding of the pathological mechanisms and disease progression. Neovascularization classification has evolved with advances in imaging technologies, from earlier classifications based on neovascularization patterns assessed by fluorescein angiography to multimodal imaging patterns, resulting in varied descriptions of lesions depending on the techniques used. Until recently, there has been a lack of consensus regarding the clinical features of choroidal neovascularization lesion types as a result of the imaging modalities initially used to define them; a recent consensus on classification has the potential to simplify and clarify descriptions of neovascularization in nAMD. The use of multimodal imaging techniques will improve lesion identification and has the potential to individualize treatment plans and improve outcomes. Conclusions: Widespread adoption of a consensus-based, image-guided classification system for neovascular lesions in nAMD and the appropriate imaging techniques used to identify them will aid clinical research and could potentially improve patient outcomes by individualizing treatment plans in the future.},
}
@article {pmid39539617,
year = {2024},
author = {Hao, XD and Xu, WH and Zhang, X and Xue, J},
title = {Targeting ferroptosis: a novel therapeutic strategy for the treatment of retinal diseases.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1489877},
pmid = {39539617},
issn = {1663-9812},
abstract = {Ferroptosis plays a vital role in the progression of various retinal diseases. The analysis of the mechanism of retinal cell ferroptosis has brought new targeted strategies for treating retinal vascular diseases, retinal degeneration and retinal nerve diseases, and is also a major scientific issue in the field of ferroptosis. In this review, we summarized results from currently available in vivo and in vitro studies of multiple eye disease models, clarified the pathological role and molecular mechanism of ferroptosis in retinal diseases, summed up the existing pharmacological agents targeting ferroptosis in retinal diseases as well as highlighting where future research efforts should be directed for the application of ferroptosis targeting agents. This review indicates that ferroptosis of retinal cells is involved in the progression of age-related/inherited macular degeneration, blue light-induced retinal degeneration, glaucoma, diabetic retinopathy, and retinal damage caused by retinal ischemia-reperfusion via multiple molecular mechanisms. Nearly 20 agents or extracts, including iron chelators and transporters, antioxidants, pharmacodynamic elements from traditional Chinese medicine, ferroptosis-related protein inhibitors, and neuroprotective agents, have a remissioning effect on retinal disease in animal models via ferroptosis inhibition. However, just a limited number of agents have received approval or are undergoing clinical trials for conditions such as iron overload-related diseases. The application of most ferroptosis-targeting agents in retinal diseases is still in the preclinical stage, and there are no clinical trials yet. Future research should focus on the development of more potent ferroptosis inhibitors, improved drug properties, and ideally clinical testing related to retinal diseases.},
}
@article {pmid39538001,
year = {2025},
author = {Corradetti, G and Karamat, A and Srinivas, S and Lindenberg, S and Velaga, SB and Corvi, F and Attiku, Y and Nittala, MG and Desai, D and Zhu, L and Abulon, D and Sadda, SR},
title = {Progression to complete retinal pigment epithelium and outer retinal atrophy (cRORA): post hoc analysis of the GATHER1 trial.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {3},
pages = {669-677},
pmid = {39538001},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology ; Double-Blind Method ; Disease Progression ; Male ; Female ; Prospective Studies ; *Geographic Atrophy/diagnosis/drug therapy ; Aged ; Fluorescein Angiography/methods ; Follow-Up Studies ; *Visual Acuity ; Fundus Oculi ; Intravitreal Injections ; Middle Aged ; Atrophy ; Time Factors ; },
abstract = {PURPOSE: Determine rates of progression of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) to complete retinal pigment epithelium and outer retinal atrophy (cRORA) and rates of progression of drusen to iRORA/cRORA in eyes with geographic atrophy (GA) treated with avacincaptad pegol (ACP).<br><br>METHODS: Post hoc analysis of the GATHER1 prospective, randomized, double-masked Phase II/III study that evaluated ACP 2&#xa0;mg vs. sham. Optical coherence tomography (OCT) data from GATHER1 were transferred to the Doheny Image Reading and Research Lab for masked analysis by readers experienced with Classification of Atrophy Meeting (CAM) grading features. Regions of OCT volume scans more than 500&#xa0;&#xb5;m from the border of GA lesions were evaluated at baseline and at months 6, 12, and 18. Participants with iRORA and/or drusen (&#x2265;&#x2009;40&#xa0;&#xb5;m height on OCT) at baseline were included in the analysis.<br><br>RESULTS: The proportion of eyes progressing from iRORA to cRORA in the ACP 2&#xa0;mg group was 5.0%, 15.0%, and 20.0% at months 6, 12, and 18 respectively, as compared with 11.8%, 30.2%, and 41.8% of eyes in the sham group. The proportion of ACP 2&#xa0;mg-treated eyes progressing from drusen to iRORA or cRORA was 3.8%, 7.6%, and 7.6% at months 6, 12, and 18 compared with 15.9%, 18.1%, and 27.2% of sham-treated eyes.<br><br>CONCLUSIONS: Rates of progression from iRORA to cRORA and drusen to iRORA/cRORA were reduced in eyes treated with ACP 2&#xa0;mg vs. sham, with increasing separation between groups over time, suggesting early intervention may slow disease progression.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02686658. Date of registration: February 16, 2016.<br><br>KEY MESSAGES: What is known Geographic atrophy is an advanced form of age-related macular&#xa0;degeneration (AMD) that leads to irreversible vision loss, presenting a significant public health unmet need. The Classification of Atrophy Meeting (CAM) group recommended a new nomenclature for advanced AMD lesions, based on the affected anatomical layers on optical coherence tomography. Accordingly, the terms incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) were introduced (Guymer et al., Ophthalmology 127:394-409, 2020; Sadda et al., Ophthalmology 125:537-548, 2018). What is new GATHER1 post hoc analysis shows that treatment with avacincaptad pegol (ACP) 2&#xa0;mg decreases the proportion of eyes that progress from iRORA to cRORA, and from drusen to iRORA or cRORA, compared with sham, over 6, 12, and 18&#xa0;months. These findings suggest a potential role for ACP in delaying the progression of existing pre-atrophic AMD lesions.},
}
@article {pmid39537399,
year = {2024},
author = {Gao, Y and Xiong, F and Xiong, J and Chen, Z and Lin, Y and Xia, X and Yang, Y and Li, G and Hu, Y},
title = {Recent advances in the application of artificial intelligence in age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {39537399},
issn = {2397-3269},
mesh = {Humans ; *Artificial Intelligence ; *Macular Degeneration/diagnosis/therapy ; },
abstract = {Recent advancements in ophthalmology have been driven by the incorporation of artificial intelligence (AI), especially in diagnosing, monitoring treatment and predicting outcomes for age-related macular degeneration (AMD). AMD is a leading cause of irreversible vision loss worldwide, and its increasing prevalence among the ageing population presents a significant challenge for managing the disease. AI holds considerable promise in tackling this issue. This paper provides an overview of the latest developments in AI applications for AMD. However, current limitations include insufficient and unbalanced data, lack of interpretability in models, dependence on data quality and limited generality.},
}
@article {pmid39524844,
year = {2024},
author = {Choi, JA and Seo, BR and Koh, JY and Yoon, YH},
title = {Protective effect of zinc against A2E-induced toxicity in ARPE-19 cells: Possible involvement of lysosomal acidification.},
journal = {Heliyon},
volume = {10},
number = {21},
pages = {e39100},
pmid = {39524844},
issn = {2405-8440},
abstract = {A key pathogenic mechanism of dry age-related macular degeneration (AMD) is lysosomal dysfunction in retinal pigment epithelium (RPE) cells, which results in the accumulation of lipofuscins such as A2E (N-retinylidene-N-retinylethanolamine) that further compromises lysosomal function. This vicious cycle leads to cell death and poor visual acuity. Here, we established an in vitro model of AMD by treating a human RPE cell line (ARPE-19) with A2E and examined whether raising zinc levels confers protective effects against lysosomal dysfunction and cytotoxicity. MTT assay showed that A2E induced apoptosis in ARPE-19 cells. pHrodo™ Red fluorescence staining showed that lysosomal pH increased in A2E-treated ARPE-19 cells. Treatment with a zinc ionophore (clioquinol) reduced A2E accumulation, restored lysosomal pH to the acidic range, and reduced A2E-induced cell death, all of which were reversed by the addition of a zinc chelator (TPEN). Consistent with the in vitro results, subretinal injections of A2E in mouse eyes resulted in the death of RPE cells as well as lysosomal dysfunction, all of which were reversed by co-treatment with clioquinol. Our results suggest that restoring the levels of intracellular zinc, especially in lysosomes, would be helpful in mitigating A2E-induced cytotoxic changes including lysosomal dysfunction in RPE cells in the pathogenesis of AMD.},
}
@article {pmid39535745,
year = {2024},
author = {Diack, C and Avery, RL and Cheung, CMG and Csaky, KG and Gibiansky, L and Jaminion, F and Gibiansky, E and Sickert, D and Stoilov, I and Cosson, V and Bogman, K},
title = {Ocular Pharmacodynamics of Intravitreal Faricimab in Patients With Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {11},
pages = {13},
pmid = {39535745},
issn = {2164-2591},
mesh = {Humans ; *Macular Edema/drug therapy/metabolism ; *Diabetic Retinopathy/drug therapy/metabolism ; *Angiopoietin-2/antagonists &amp; inhibitors/metabolism ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Intravitreal Injections ; *Aqueous Humor/metabolism/drug effects ; Male ; Female ; Aged ; *Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage/therapeutic use/pharmacology ; Antibodies, Bispecific/pharmacokinetics/administration &amp; dosage/pharmacology/therapeutic use ; Middle Aged ; Wet Macular Degeneration/drug therapy/metabolism ; Visual Acuity/drug effects ; Aged, 80 and over ; Vesicular Transport Proteins ; },
abstract = {PURPOSE: Evaluate the ocular pharmacodynamics (PD) of intravitreal faricimab, a bispecific inhibitor of angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).<br><br>METHODS: Aqueous humor (AH) samples (1025 free Ang-2 concentrations and 1345 free VEGF-A concentrations) were collected from approximately 300 faricimab-treated patients with nAMD or DME in phase&#xa0;2/3 trials. A population pharmacokinetic pharmacodynamic (popPKPD) model was developed to describe the dynamic effect of faricimab on free AH Ang-2 and VEGF-A.<br><br>RESULTS: Mean baseline Ang-2 concentrations were 8.1 and 13.4&#xa0;pg/mL in patients with nAMD and DME, respectively. The corresponding mean baseline VEGF-A concentrations were 58 and 135&#xa0;pg/mL, respectively. Overall, approximately 79% of Ang-2 (84% within 8 weeks postdose and 55% beyond 12 weeks postdose) and 7% of VEGF-A postdose observations were below the lower limit of quantification. Model-derived Ang-2 and VEGF-A concentration-time profiles for patients on every 4-week/every 8-week dosing were predicted to maintain greater than 50% suppression of Ang-2 concentrations for the entire dosing period. Patients on every 12-week/16-week dosing were predicted to have greater than 50% Ang-2 suppression for 12 or more weeks, whereas 50% VEGF-A suppression was maintained for 9 to 10 weeks. At 8 weeks postdose, the median Ang-2 concentrations remained suppressed by approximately 80%. At 16 weeks postdose, the median VEGF-A concentrations returned to baseline, but median Ang-2 levels remained below baseline.<br><br>CONCLUSIONS: A popPKPD analysis demonstrated faricimab's rapid and sustained suppression of AH Ang-2 and VEGF-A.<br><br>TRANSLATIONAL RELEVANCE: A popPKPD analysis suggested that sustained suppression of ocular Ang-2 contributes to faricimab's extended durability, observed in clinical trials.},
}
@article {pmid39535744,
year = {2024},
author = {Diack, C and Gibiansky, L and Jaminion, F and Gibiansky, E and Gaudreault, J and Bogman, K and Cosson, V},
title = {Ocular Pharmacokinetics of Faricimab Following Intravitreal Administration in Patients With Retinal Disease.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {11},
pages = {14},
pmid = {39535744},
issn = {2164-2591},
mesh = {Humans ; *Intravitreal Injections ; Male ; Female ; Aged ; Middle Aged ; *Aqueous Humor/metabolism ; Aged, 80 and over ; Macular Edema/drug therapy ; Diabetic Retinopathy/drug therapy ; Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage/therapeutic use ; Half-Life ; },
abstract = {PURPOSE: To characterize faricimab ocular and systemic pharmacokinetics (PK) in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) and to assess the effect of faricimab ocular exposure on clinical endpoints.<br><br>METHODS: A population PK (popPK) model was developed using pooled data from phase 1 to 3 studies in patients with nAMD/DME. The dataset included 1095 faricimab aqueous humor (AH) concentrations from 284 patients and 8372 faricimab plasma concentrations from 2246 patients.<br><br>RESULTS: Following intravitreal administration, faricimab PK was accurately described by a linear three-compartment model with sequential vitreous humor (VH), AH, and plasma compartments. Faricimab VH elimination to AH is the slowest process, with an estimated half-life (t1/2) of 7.5 days. Due to flip-flop kinetics, plasma, AH, and VH concentrations declined in parallel. Disease had no effect on faricimab PK. Plasma exposure was &#x223c;6000-fold lower than VH exposure. Age, anti-drug antibodies, body weight, and sex statistically significantly influenced PK parameters but had no clinically meaningful effect on ocular and systemic exposure. VH t1/2 alone could not explain faricimab dosing frequency. Exposure-response analyses showed similar gains in best-corrected visual acuity across faricimab exposure ranges and dosing regimens.<br><br>CONCLUSIONS: Faricimab ocular and systemic pharmacokinetics were quantified and accurately described by the popPK model, developed using a large dataset from patients with nAMD/DME. Exposure-response analyses suggest that faricimab phase 3 dosing algorithms are appropriate to select the most suitable dosing regimen.<br><br>TRANSLATIONAL RELEVANCE: The popPK analysis suggested that faricimab dosing frequency was influenced by several factors and not by VH t1/2 alone.},
}
@article {pmid39535413,
year = {2025},
author = {Rahhal, FM and Hu, A and Humayun, M and George, MS and Javid, C and Brown, J and Pitcher, JD and Dagnon, T and Kissner, J},
title = {ONS-5010 (bevacizumab-vikg) Safety and Efficacy in Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {3},
pages = {178-189},
doi = {10.3928/23258160-20240924-01},
pmid = {39535413},
issn = {2325-8179},
mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage/adverse effects ; *Bevacizumab/administration &amp; dosage/therapeutic use/adverse effects ; Male ; Visual Acuity/physiology ; Double-Blind Method ; Female ; Aged ; Prospective Studies ; Middle Aged ; *Choroidal Neovascularization/drug therapy/etiology/diagnosis ; *Wet Macular Degeneration/drug therapy/complications/diagnosis/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Tomography, Optical Coherence ; Aged, 80 and over ; Fluorescein Angiography ; Fovea Centralis ; Ranibizumab ; Follow-Up Studies ; },
abstract = {BACKGROUND AND OBJECTIVE: This was a prospective multicenter, randomized, double-masked, active-controlled study, the aim of which was to demonstrate the efficacy and safety of intravitreal ONS-5010 (bevacizumab-vikg) in eyes with neovascular age-related macular degeneration (nAMD). This was a phase III trial on ONS-5010 (NORSE TWO).<br><br>MATERIALS AND METHODS: Treatment-na&#xef;ve nAMD patients aged 50 years and older with a best-corrected distance visual acuity (BCVA) of 25 to 67 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and evidence of disease activity were included. Patients randomized to ONS-5010 received monthly intravitreal doses of 1.25 mg of ONS-5010, bevacizumab-vikg (Outlook Therapeutics) for 12 months. Patients randomized to ranibizumab received 0.50 mg of ranibizumab on days 0, 30, 60, 150, and 240 based on the PIER study dosing regimen.<br><br>RESULTS: The primary end point was the proportion of patients who gained &#x2265; 15 letters from baseline in BCVA at 11 months, and evaluating the safety and tolerability of intravitreal injections of ONS-5010 administered monthly from baseline to 12 months. One hundred thirteen participants were included in the ONS-5010 group and 115 participants were included in the ranibizumab group. Respectively, 41.7% and 23.1% of patients gained &#x2265; 15 letters (3 lines) of visual acuity, with a risk difference of 0.1859 [95% CI = 0.0442, 0.3086]; P = 0.0052. The change in BCVA from baseline to 11 months was found to be 11.2 &#xb1; 12.19 and 5.8 &#xb1; 14.80 ETDRS letters, respectively. The number of patients gaining &#x2265; 5 and &#x2265; 10 letters and patients losing < 15 letters was significantly higher in the ONS-5010 group. Similarly, patients with a Snellen visual acuity equivalent of 20/200 (35 ETDRS letters) or worse at 11 months were significantly fewer in the ONS-5010 group. Only one patient in the ONS-5010 group had a study-related serious ocular adverse event (SAE), namely, elevated intraocular pressure. The most common adverse event in the ONS-5010 group was conjunctival hemorrhage (8.8%), and reduced visual acuity in the ranibizumab group (12.2%).<br><br>CONCLUSIONS: In the prescribed treatment plan, ONS-5010 exhibited strong effectiveness in improving or stabilizing visual acuity and was also well tolerated. Bevacizumab and ranibizumab displayed a comparable safety profile. [Ophthalmic Surg Lasers Imaging Retina 2025;56:178-189.].},
}
@article {pmid39533430,
year = {2024},
author = {Zhang, M and Lu, X and Luo, L and Dou, J and Zhang, J and Li, G and Zhao, L and Sun, F},
title = {Targeting glutamine synthetase with AS1411-modified exosome-liposome hybrid nanoparticles for inhibition of choroidal neovascularization.},
journal = {Journal of nanobiotechnology},
volume = {22},
number = {1},
pages = {703},
pmid = {39533430},
issn = {1477-3155},
support = {No.20220402036GH, No.20210402045GH//Jilin Province Science and Technology Development Plan Project/ ; },
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Humans ; Rabbits ; *Liposomes/chemistry ; *Nanoparticles/chemistry ; *Exosomes/metabolism ; *Human Umbilical Vein Endothelial Cells ; *Aptamers, Nucleotide/pharmacology/chemistry ; *Glutamate-Ammonia Ligase/metabolism ; *Oligodeoxyribonucleotides/chemistry/pharmacology ; CRISPR-Cas Systems ; Gene Editing/methods ; Male ; },
abstract = {Choroidal neovascularization (CNV) is a leading cause of visual impairment in wet age-related macular degeneration (wAMD). Recent investigations have validated the potential of reducing glutamine synthetase (GS) to inhibit neovascularization formation, offering prospects for treating various neovascularization-related diseases. In this study, we devised a CRISPR/Cas9 delivery system employing the nucleic acid aptamer AS1411 as a targeting moiety and exosome-liposome hybrid nanoparticles as carriers (CAELN). Exploiting the binding affinity between AS1411 and nucleolin on endothelial cell surfaces, the delivery system was engineered to specifically target the glutamine synthetase gene (GLUL), thereby attenuating GS levels and continuously suppressing CNV. CAELN exhibited spherical and uniform dispersion. In vitro cellular investigations demonstrated gene editing efficiencies of CAELN ranging from 42.05 to 55.02% and its capacity to inhibit neovascularization in HUVEC cells. Moreover, in vivo pharmacodynamic studies conducted in CNV rabbits revealed efficacy of CAELN in restoring the thickness of intra- and extranuclear tissues. The findings suggest that GS is a novel target for the inhibition of pathological CNV, while the development of AS1411-modified exosome-liposome hybrid nanoparticles represents a novel delivery method for the treatment of neovascular-related diseases.},
}
@article {pmid39532510,
year = {2025},
author = {Paris, A and Volpe, G and Perruchoud-Ader, K and Casanova, A and Menghini, M and Grimaldi, G},
title = {Short-term intraocular pressure changes after intravitreal aflibercept 2 mg, aflibercept 8 mg and faricimab: a prospective, comparative study.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {5},
pages = {600-605},
pmid = {39532510},
issn = {1468-2079},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Prospective Studies ; Intravitreal Injections ; Female ; Male ; *Intraocular Pressure/drug effects ; Aged ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Diabetic Retinopathy/drug therapy/physiopathology ; *Macular Edema/drug therapy/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tonometry, Ocular ; Visual Acuity ; Middle Aged ; Aged, 80 and over ; *Macular Degeneration/drug therapy/physiopathology ; Follow-Up Studies ; *Ocular Hypertension/chemically induced/physiopathology ; Antibodies, Bispecific ; },
abstract = {BACKGROUND/AIMS: Intravitreal injection (IVT) of anti-vascular endothelial growth factor agents is the standard of care for several retinal diseases but can cause intraocular pressure (IOP) elevations. This study investigates short-term postinjection IOP changes following aflibercept 8 mg and faricimab, compared with aflibercept 2 mg.<br><br>METHODS: This observational, prospective study included 90 patients with age-related macular degeneration or diabetic macular oedema, divided into three groups, receiving aflibercept 2&#x2009;mg, aflibercept 8&#x2009;mg or faricimab. IOP was measured using an iCare IC200-tonometer preinjection (T0) and at 30&#x2009;s (T1), 5&#x2009;min (T2) and 15&#x2009;min (T3) postinjection. Primary outcomes included IOP changes at the four time points within and between treatment groups. The incidence of transient visual loss requiring paracentesis was recorded.<br><br>RESULTS: All groups experienced a significant IOP increase at T1, with mean IOP increase being 41.47&#xb1;12.95&#x2009;mm Hg for aflibercept 2&#x2009;mg, 43.46&#xb1;8.97&#x2009;mm Hg for aflibercept 8&#x2009;mg and 32.19&#xb1;11.06&#x2009;mm Hg for faricimab. By T2, IOP differences were not significant, and by T3, mean IOP returned within normal limits across all groups. Faricimab showed a smaller initial IOP spike than both aflibercept formulations, but this difference was not statistically significant at T2 and T3.<br><br>CONCLUSION: Transient IOP spikes are observed post-IVT of aflibercept 8&#x2009;mg and faricimab, with similar trends to aflibercept 2&#x2009;mg. The initial IOP elevation normalised within 15&#x2009;min. Faricimab had a lower initial spike, but overall IOP profiles were comparable across different agents.},
}
@article {pmid39532220,
year = {2025},
author = {Xiong, S and Xie, J and Xiang, F and Yu, J and Li, Y and Xia, B and Zhang, Z and Li, C and Lin, L},
title = {Research progress on pharmacological effects against liver and eye diseases of flavonoids present in Chrysanthum indicum L., Chrysanthemum morifolium Ramat., Buddleja officinalis Maxim. and Sophora japonica L.},
journal = {Journal of ethnopharmacology},
volume = {338},
number = {Pt 2},
pages = {119094},
doi = {10.1016/j.jep.2024.119094},
pmid = {39532220},
issn = {1872-7573},
mesh = {*Flavonoids/pharmacology/isolation &amp; purification ; Humans ; Animals ; *Chrysanthemum/chemistry ; *Liver Diseases/drug therapy/metabolism ; *Sophora/chemistry ; *Flowers/chemistry ; *Eye Diseases/drug therapy ; Plant Extracts/pharmacology/therapeutic use ; Sophora japonica ; },
abstract = {Chrysanthemum indicum L., Chrysanthemum morifolium Ramat., Buddleja officinalis Maxim., and Sophora japonica L. have the effects of "Clearing the liver" and "Improving vision". Flavonoids are their main active ingredients, but there are few reports on their simultaneous liver and eye protective effects.<br><br>AIM OF THE STUDY: Overview of the role of flavonoids of the four medicinal flowers (FFMF) in the prevention and treatment of liver and eye diseases.<br><br>MATERIALS AND METHODS: The Web of Science, PubMed, CNKI, Google Scholar, and WanFang databases were searched for FFMF. Using "hepatitis", "liver fibrosis", "liver cancer", "dry eye syndrome", "cataracts", "glaucoma", "age-related macular degeneration", and "diabetic retinopathy" as the keywords, we summarized the main pathological mechanisms of these diseases and the role of FFMF in their prevention and treatment.<br><br>RESULTS: We found that the four medicinal flowers contained a total of 125 flavonoids. They can maintain liver and eye homeostasis by regulating pathological mechanisms such as oxidative stress, inflammation, endoplasmic reticulum stress, mitochondrial dysfunction, glucose and lipid metabolism disorders, and programmed cell death, exerting the effect of "clearing the liver and improving vision".<br><br>CONCLUSION: FFMF have a series of beneficial properties such as antioxidant, anti-inflammatory, antiviral, and antifibrotic activity, and the regulation of angiogenesis, glycolipid metabolism and programmed cell death, which may explain the efficacy of the four traditional Chinese medicines for "Clearing the liver" and "Improving vision".},
}
@article {pmid39532089,
year = {2025},
author = {Dey, PN and Singh, N and Zelinger, L and Batz, Z and Nellissery, J and White Carreiro, ND and Qian, H and Li, T and Fariss, RN and Dong, L and Swaroop, A},
title = {Loss of paired immunoglobin-like type 2 receptor B gene associated with age-related macular degeneration impairs photoreceptor function in mouse retina.},
journal = {Human molecular genetics},
volume = {34},
number = {1},
pages = {64-76},
pmid = {39532089},
issn = {1460-2083},
support = {ZIA EY000450/ImNIH/Intramural NIH HHS/United States ; ZIA EY000456/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Macular Degeneration/genetics/metabolism/pathology ; Retina/metabolism/pathology ; Mice, Knockout ; *Receptors, Immunologic/genetics/metabolism ; *Photoreceptor Cells, Vertebrate/metabolism/pathology ; Electroretinography ; Disease Models, Animal ; Humans ; Genome-Wide Association Study ; },
abstract = {Genome-wide association studies have uncovered mostly non-coding variants at over 60 genetic loci linked to susceptibility for age-related macular degeneration (AMD). To ascertain the causal gene at the PILRB/PILRA locus, we used a CRISPR strategy to produce germline deletions in the mouse paired immunoglobin-like type 2 receptor (Pilr) genes that encode highly related activating (PILRB) and inhibitory (PILRA) receptors. We show that a combined loss of Pilrb1 and Pilrb2, but not Pilra, leads to an early but relatively stationary defect as the electroretinography (ERG) amplitudes of Pilrb1/2-/- mice exhibit a marked reduction as early as postnatal day 15 and do not show additional significant decrease at 3 and 12-months. No alterations are evident in Müller glia, microglia, bipolar, amacrine and horizontal cells based on immunohistochemistry using cell-type specific markers. PILRB immunostaining is specifically detected at the proximal part of photoreceptor outer segment. Reduced expression of select calcium-regulated phototransduction and synapse-associated proteins, including GCAP1 and 2, PDE6b, AIPL1, PSD95, and CTBP1 indicates dysregulation of calcium homeostasis as a possible mechanism of retinal phenotype in Pilrb1/2-/- mice. Our studies suggest a novel function of PILRB in retinal photoreceptors and an association of PILRB, but not PILRA, with AMD pathogenesis.},
}
@article {pmid39531588,
year = {2025},
author = {Hashemi, H and Pakzad, R and Aghamirsalim, M and Hashemi, A and Khabazkhoob, M},
title = {Decomposition of Economic Inequality in Age-Related Macular Degeneration by Using Oaxaca-Blinder Decomposition: Tehran Geriatric Eye Study.},
journal = {Ophthalmic epidemiology},
volume = {32},
number = {4},
pages = {446-454},
doi = {10.1080/09286586.2024.2415047},
pmid = {39531588},
issn = {1744-5086},
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; Aged ; Iran/epidemiology ; Middle Aged ; *Macular Degeneration/epidemiology/economics ; Prevalence ; Aged, 80 and over ; Socioeconomic Factors ; },
abstract = {PURPOSE: To investigate economic inequality in age-related macular degeneration (AMD) and decompose it into its determinants using Oaxaca-Blinder decomposition (OBD).<br><br>METHODS: The Tehran Geriatric Eye Study was a cross-sectional study conducted on individuals aged 60 years and older, utilizing stratified random cluster sampling. Each participant received a comprehensive optometric, and slit-lamp examination. Diagnosis and classification of AMD were conducted utilizing fundus camera images.<br><br>RESULTS: The data of the 3268 participants were analyzed. According to OBD, a significant difference was found in AMD between the rich and poor groups (8.36%) disfavoring the poor (p < 0.001). The explained and unexplained portions comprised 93.37% and 6.63% of the difference (p < 0.001 and p = 0.405, respectively). Among study variables, age (coefficient = 4.70; p < 0.001), economic status (coefficient = 3.58; p = 0.004), and myopia (coefficient = 0.73; p = 0.001) were significant determinants of inequality in the explained portion.<br><br>CONCLUSION: A significant disparity in the prevalence of AMD was observed between individuals of different socioeconomic statuses, primarily attributed to the explained factors. Factors such as age, economic status, and myopia were found to have the most substantial impact in exacerbating the inequality that disadvantaged the poor group (contributing percentages: 52.17%, 39.73%, and 8.10%, respectively). The findings of this research can be valuable for health policymakers in prioritizing and addressing the determinants of inequality within the population.},
}
@article {pmid39531583,
year = {2025},
author = {Ambati, NR and Leone, A and Brill, D and Sisk, RA},
title = {REAL-WORLD LONG-TERM OUTCOMES OF INTRAVITREAL FARICIMAB IN PREVIOUSLY TREATED CHRONIC NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {3},
pages = {446-453},
pmid = {39531583},
issn = {1539-2864},
mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Female ; Male ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Follow-Up Studies ; Fluorescein Angiography/methods ; Aged, 80 and over ; Treatment Outcome ; Time Factors ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Chronic Disease ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To study the real-world outcomes of intravitreal faricimab (IVF) in long-standing neovascular age-related macular degeneration (nAMD) over a 1-year study period.<br><br>METHODS: Retrospective single-center cohort study of patients with previously treated nAMD receiving IVF with at least 12 months of follow-up. Main outcome measures include injection intervals, visual acuity (VA), and optical coherence tomography features.<br><br>RESULTS: A total of 263 eyes from 217 patients received 6.4 &#xb1; 2.3 IVF injections over 1 year. Injection interval increased after switching to IVF (5.9 &#xb1; 1.8 vs. 7.6 &#xb1; 2.4 weeks) (P < 0.01). There was no improvement in VA after switching to IVF at any time period (P > 0.15). Average CST decreased after the first IVF injection and was sustained for 1 year (313.7 &#xb1; 96.0 vs. 288.2 &#xb1; 80.6 &#xb5; m) (P < 0.01). There was a statistically significant resolution of subretinal fluid but not IRF at all time points (40.8%-50.4%; P < 0.01). Persistent fluid after the first IVF injection was resolved in 34.4% (n = 45) by 1 year. IVF was discontinued in 31 eyes (11.8%), four (1.6%) that experienced intraocular inflammation.<br><br>CONCLUSION: Long-standing nAMD eyes switched to IVF experienced a significant extension in injection interval, stable visual acuity, improvement in CST, and resolution of fluid on OCT in many patients over 1 year.},
}
@article {pmid39531304,
year = {2024},
author = {Merkulova, GA and Pestryakova, YF},
title = {[Application of the functional-topical diagnostic method to identify the pathological process in patients with age-related macular degeneration.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {37},
number = {4},
pages = {436-441},
pmid = {39531304},
issn = {1561-9125},
mesh = {Humans ; *Macular Degeneration/diagnosis/physiopathology ; Aged ; Male ; Female ; Prognosis ; Early Diagnosis ; Middle Aged ; },
abstract = {Along with increasing life expectancy and aging of the population, there is an increase in the incidence of age-related macular degeneration (AMD), which often leads to blindness or irreversible vision loss and has a pronounced impact on the quality of life. Application of an extended complex of diagnostic techniques in ophthalmologic practice in order to expand the possibilities of early diagnosis and prognosis of the disease is urgent. Screening examination of patients with AMD was carried out. The technology of registration of global rhythmic activity of the brain with narrow-band filtering and long summation time was applied with the allocation of mainly long-lasting rhythmic oscillations in the frequency spectrum of 0,1-30 Hz. The peculiarities of the state of autonomic receptors of the eye in AMD have been determined. The prognostically significant signs of changes in the spectrum of the brain activating system at early and late stages of AMD were identified. The information characteristic of the weight of the sign of AMD development was obtained; that allowed to distinguish the ophthalmologic status of patients with AMD. The use of functional-topical diagnostics based on spectral analysis of rhythmic brain activity can be used as an additional non-invasive diagnostic screening test for early development of AMD, which will ensure timely and competently prescribed treatment and allow to achieve better long-term clinical outcomes.},
}
@article {pmid39531303,
year = {2024},
author = {Agarkov, NM and Popova, NV and Korovin, EN and Kurzin, ML},
title = {[The relationship of exudative age-related macular degeneration with lacrimal fluid chemokines in elderly patients.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {37},
number = {4},
pages = {430-435},
pmid = {39531303},
issn = {1561-9125},
mesh = {Humans ; Aged ; Male ; Female ; Middle Aged ; *Chemokines/metabolism/analysis ; *Tears/metabolism ; Macular Degeneration/diagnosis/metabolism ; Wet Macular Degeneration/diagnosis/metabolism ; Chemokine CCL2/analysis/metabolism ; },
abstract = {Age-related macular degeneration (AMD), along with other age-associated ophthalmologies, is a significant cause of loss of visual functions among the elderly, but the relationship of exudative AMD with lacrimal fluid chemokines has not been sufficiently studied. The aim of the work was to study the relationship of exudative AMD with lacrimal fluid chemokines in elderly patients. The content of chemokines in the lacrimal fluid was studied in 92 patients (184 eyes) 60-74 years old with exudative AMD and 84 patients (168 eyes) 60-74 years old without ophthalmopathology using a certified MAGRIX (USA) immunoassay device with Luminex technology on the xMAX platform. AMD diagnosis was performed based on the results of a comprehensive ophthalmological examination and in accordance with the classification criteria (Age-Related Eye Disease Study). Regression analysis and the program Statistica 10.0 were used in the processing of the obtained data. An increase in the production of most of the considered chemokines in patients with exudative AMD in lacrimal fluid was found in relation to representatives of the same age without ophthalmopathology, namely: MCP-1/CCL2 to 712,4±3,4 pg/ml reference 598,6±3,1 pg/ml (p<0,01), IP-10/CXCL10 to 37,9±2,6 pg/ml reference 11,3±2,3 pg/ml (p<0,001), SDF-1α/CXCL12 to 262,5±4,3 pg/ml reference 208,2±4,7 pg/ml (p<0,001), Eotaxin/CCL11 to 6,2±0,4 pg/ml reference 4,3±0,6 pg/ml (p<0,01), RANTES/CCL5 to 1,7±0,3 versus 0,6±0,2 pg/ml (p<0,001). On the contrary, the content of MIP-1a/CCL3 chemokines decreased to 2±0,3 versus 4,1±0,5 pg/ml (p<0,001), GROa/CXCL1 to 7,2±0,9 versus 15,8±2,1 pg/ml (p<0,001). The coefficients of the performed multidimensional regression analysis turned out to be the highest for IP-10/CXCL10 (β=+3,538), RANTES/CCL5 - (β=+2,859) and GROa/CXCL1 - (β=-2,419), which indicates the greatest association of these lacrimal fluid chemokines with the development of exudative AMD. These lacrimal fluid chemokines can be used as additional diagnostic markers of exudative AMD.},
}
@article {pmid39529696,
year = {2024},
author = {Savant, SV and Kwan, JT and Barouch, F and Chang, J and Ramsey, DJ and Marx, J and Blaha, G and Klein-Mascia, K},
title = {Durability and Efficacy of Faricimab in Treatment-Resistant Retinal Edema Utilizing "Real-World" Dosing Regimens.},
journal = {Journal of ophthalmology},
volume = {2024},
number = {},
pages = {8583348},
pmid = {39529696},
issn = {2090-004X},
abstract = {Purpose: To retrospectively analyze clinical outcomes of patients with "treatment-resistant" neovascular age-related macular degeneration or diabetic macular edema who were switched to intravitreal faricimab injections (IFIs) using a "real-world" treat-and-extend (TAE) protocol. Methods: Seventy-one eyes from 62 patients receiving antivascular endothelial growth factor injections were evaluated before and after switching to IFI. Demographic and clinical data were collected. Primary endpoints were treatment interval extension and presence of intraretinal or subretinal fluid on spectral-domain optical coherence tomography (OCT) after switching to IFI. Secondary endpoints included best-corrected visual acuity, average OCT central subfield thickness, and presence of a pigment epithelium detachment and pigment epithelium detachment height. Results: The average treatment interval after switching to IFI significantly increased from 37.6 ± 10.8 days to 45.2 ± 16.6 days (p = 0.0016). At the last follow-up, 35% of eyes were able to achieve a fluid-free status post-IFI. A chi-square test of independence validated this finding by showing a significant difference in the OCT findings trending towards less or no fluid on follow-up (X [2] [3, N = 71] = 13.0705; p = 0.0003). The average central subfield thickness decreased from 327.2 ± 89.1 μm to 294.8 ± 86.5 μm (p = 0.0294). Best-corrected visual acuity, intraocular pressure, pigment epithelium detachment presence, and height had no significant difference after switching to IFI. Conclusions: In "treatment-resistant" patients receiving anti-VEGF therapy for neovascular age-related macular degeneration or diabetic macular edema, switching to IFI in a "real-world" TAE protocol led to statistically significant improvements in treatment interval and retinal fluid on spectral domain OCT.},
}
@article {pmid39528811,
year = {2025},
author = {Horozoglu Ceran, T and Sonmez, K and Kirtil, G},
title = {The impact of vitreomacular traction on vitreous vascular endothelial growth factor and placental growth factor levels in neovascular age-related macular degeneration patients.},
journal = {Eye (London, England)},
volume = {39},
number = {2},
pages = {373-378},
pmid = {39528811},
issn = {1476-5454},
mesh = {Humans ; *Placenta Growth Factor/metabolism ; *Vitreous Body/metabolism/pathology ; *Vascular Endothelial Growth Factor A/metabolism ; Prospective Studies ; Female ; Male ; Case-Control Studies ; Aged ; *Wet Macular Degeneration/metabolism ; Aged, 80 and over ; Tissue Adhesions ; Middle Aged ; },
abstract = {PURPOSE: To investigate the effect of vitreomacular traction (VMT) on vitreous vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels in patients with active neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: A prospective, interventional, case-control study.<br><br>METHODS: The study included a total of 70 patients from whom vitreous samples were obtained. The patients were categorized into four group: 10 patients with active nAMD accompanying VMT, 17 patients with VMT, 24 patients with active nAMD and 19 healthy patients without any diagnosis other than cataract. VEGF and PlGF levels were measured.<br><br>RESULTS: The mean vitreous VEGF level was 34.7&#x2009;&#xb1;&#x2009;4.98&#x2009;pg/ml in the nAMD and VMT group, 32.36&#x2009;&#xb1;&#x2009;4.55&#x2009;pg/ml in the VMT group, 34.02&#x2009;&#xb1;&#x2009;3.79&#x2009;pg/ml in the nAMD group, and 32.33&#x2009;&#xb1;&#x2009;2.4&#x2009;pg/ml in the healthy control group. The mean vitreous PlGF level was 58.92&#x2009;&#xb1;&#x2009;20.83&#x2009;pg/ml in the nAMD and VMT group, 46.29&#x2009;&#xb1;&#x2009;3.45&#x2009;pg/ml in the VMT group, 54.64&#x2009;&#xb1;&#x2009;16.88&#x2009;pg/ml in the nAMD group, and 53.66&#x2009;&#xb1;&#x2009;19.35&#x2009;pg/ml in the healthy control group. No significant differences were observed in terms of vitreous VEGF and PlGF concentrations among the groups (p&#x2009;>&#x2009;0.05 and p&#x2009;>&#x2009;0.05, respectively). Aqueous humour VEGF and PlGF levels were significantly higher than vitreous levels in nAMD patients (p&#x2009;=&#x2009;0.005 and p&#x2009;=&#x2009;0.005, respectively).<br><br>CONCLUSION: The present study found no increases in vitreous VEGF and PlGF levels in both VMT&#x2009;+&#x2009;nAMD and VMT cases. Furthermore, patients with nAMD had significantly higher levels of PlGF and VEGF in aqueous humour compared to vitreous levels.},
}
@article {pmid39528095,
year = {2025},
author = {Jiang, X and Liu, C and Zhang, Q and Lv, Y and Lu, C and Su, W and Zhou, J and Zhang, H and Gong, H and Liu, Y and Yuan, S and Chen, Y and Qu, D},
title = {Strategic delivery of rapamycin and ranibizumab with intravitreal hydrogel depot disrupts multipathway-driven angiogenesis loop for boosted wAMD therapy.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {377},
number = {},
pages = {239-255},
doi = {10.1016/j.jconrel.2024.11.011},
pmid = {39528095},
issn = {1873-4995},
mesh = {Animals ; *Hydrogels/administration &amp; dosage ; *Ranibizumab/administration &amp; dosage ; *Sirolimus/administration &amp; dosage ; *Angiogenesis Inhibitors/administration &amp; dosage/pharmacology ; *Intravitreal Injections ; Mice, Inbred C57BL ; Wet Macular Degeneration/drug therapy ; Oxidative Stress/drug effects ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Mice ; TOR Serine-Threonine Kinases/metabolism/antagonists &amp; inhibitors ; Male ; Autophagy/drug effects ; Drug Delivery Systems ; Retinal Pigment Epithelium/drug effects/metabolism ; Angiogenesis ; },
abstract = {Autophagic dysfunction-induced deterioration of the retinal microenvironment drives the progression of wet age-related macular degeneration (wAMD). The efficacy of single-target anti-VEGF antibodies in treating wAMD has long been suboptimal due to the intricate interplay between autophagy dysfunction, oxidative stress, and angiogenesis. Here, we introduce an intravitreal hydrogel depot, named Rab&amp;Rapa-M@G, consisting of rapamycin-loaded microemulsion (Rapa-M, an mTOR inhibitor), ranibizumab (anti-VEGF antibody), and a thermosensitive hydrogel matrix. A single intravitreal injection of Rab&amp;Rapa-M@G can sustainably deliver Rapa-M and ranibizumab to the retinal pigment epithelium for at least 14 days. This formulation significantly improves retinal autophagic flux homeostasis and reduces oxidative stress injury in wAMD mice by modulating the AMPK/mTOR/HIF-1α/VEGF and AMPK/ROS/HO-1/VEGF pathways. Consequently, it synergistically disrupts the "autophagic dysfunction-oxidative stress-angiogenesis" loop, leading to a remarkable reduction in choroidal neovascularization area and retinal damage compared to ranibizumab alone. Notably, the sequential administration of ranibizumab and Rab&amp;Rapa-M@G further enhances the overall anti-wAMD efficacy, achieved through sequential delivery of Rab and Rapa, allowing for a more precise grasp of the treatment window. In conclusion, this hydrogel depot design, with its sequential and sustained delivery of mTOR inhibitors and anti-VEGF antibodies, offers a promising strategy for multi-target synergistic therapy in wAMD.},
}
@article {pmid39527566,
year = {2024},
author = {Vairetti, C and Maldonado, S and Cuitino, L and Urzua, CA},
title = {Interpretable multimodal classification for age-related macular degeneration diagnosis.},
journal = {PloS one},
volume = {19},
number = {11},
pages = {e0311811},
pmid = {39527566},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/diagnosis/classification ; *Tomography, Optical Coherence/methods ; Artificial Intelligence ; Deep Learning ; Retina/diagnostic imaging/pathology ; Multimodal Imaging/methods ; Image Processing, Computer-Assisted/methods ; },
abstract = {Explainable Artificial Intelligence (XAI) is an emerging machine learning field that has been successful in medical image analysis. Interpretable approaches are able to "unbox" the black-box decisions made by AI systems, aiding medical doctors to justify their diagnostics better. In this paper, we analyze the performance of three different XAI strategies for medical image analysis in ophthalmology. We consider a multimodal deep learning model that combines optical coherence tomography (OCT) and infrared reflectance (IR) imaging for the diagnosis of age-related macular degeneration (AMD). The classification model is able to achieve an accuracy of 0.94, performing better than other unimodal alternatives. We analyze the XAI methods in terms of their ability to identify retinal damage and ease of interpretation, concluding that grad-CAM and guided grad-CAM can be combined to have both a coarse visual justification and a fine-grained analysis of the retinal layers. We provide important insights and recommendations for practitioners on how to design automated and explainable screening tests based on the combination of two image sources.},
}
@article {pmid39527325,
year = {2024},
author = {Yang, F and Hu, R},
title = {Efficacy and safety of intravitreal conbercept and triamcinolone acetonide for wet age-related macular degeneration in China: a meta-analysis.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {424},
pmid = {39527325},
issn = {1573-2630},
mesh = {Humans ; *Triamcinolone Acetonide/administration &amp; dosage/adverse effects/therapeutic use ; *Intravitreal Injections ; *Glucocorticoids/administration &amp; dosage/therapeutic use/adverse effects ; *Visual Acuity ; China/epidemiology ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Tomography, Optical Coherence/methods ; },
abstract = {BACKGROUND: Several studies have investigated the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wet age-related macular degeneration (wAMD), but the results are controversial. Therefore, this meta-analysis aims to evaluate the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wAMD.<br><br>METHODS: A total of seven databases were searched for literature on the treatment of wAMD with Conbercept, with the search period from database inception to May 2024. Patients in the experimental group received Conbercept treatment, while patients in the control group received Triamcinolone acetonide treatment. The observed indicators included central macular thickness, incidence of adverse reactions, clinical efficacy, and best-corrected visual acuity. Relative risk (RR) and mean difference (MD) were used as effect measures.<br><br>RESULTS: A total of 12 studies with 864 patients were included in the meta-analysis. The results showed that the experimental group had a significantly better central macular thickness (MD&#x2009;=&#x2009;&#x2009;-&#x2009;42.68, 95% CI&#x2009;=&#x2009;&#x2009;-&#x2009;55.04&#x2009;~&#x2009;&#x2009;-&#x2009;30.32, P&#x2009;<&#x2009;0.001), clinical response rate (RR&#x2009;=&#x2009;1.25, 95% CI&#x2009;=&#x2009;1.12&#x2009;~&#x2009;1.39, P&#x2009;<&#x2009;0.001), and best-corrected visual acuity (MD&#x2009;=&#x2009;0.16, 95% CI&#x2009;=&#x2009;0.12&#x2009;~&#x2009;0.20, P&#x2009;<&#x2009;0.001) compared to the control group. In terms of adverse events, the overall incidence of adverse events was lower in the experimental group (RR&#x2009;=&#x2009;0.26, 95% CI&#x2009;=&#x2009;0.14&#x2009;~&#x2009;0.51, P&#x2009;<&#x2009;0.001) compared to the control group. Specifically, the incidence of intraocular pressure elevation (RR&#x2009;=&#x2009;0.33, 95% CI&#x2009;=&#x2009;0.12&#x2009;~&#x2009;0.94, P&#x2009;=&#x2009;0.04) and intraocular inflammation (RR&#x2009;=&#x2009;0.17, 95% CI&#x2009;=&#x2009;0.03&#x2009;~&#x2009;0.97, P&#x2009;=&#x2009;0.05) was lower in the experimental group compared to the control group, but there was no significant difference in the incidence of subconjunctival hemorrhage (RR&#x2009;=&#x2009;0.7, 95% CI&#x2009;=&#x2009;0.14&#x2009;~&#x2009;3.5, P&#x2009;=&#x2009;0.66) and corneal edema (RR&#x2009;=&#x2009;0.2, 95% CI&#x2009;=&#x2009;0.04&#x2009;~&#x2009;1.12, P&#x2009;=&#x2009;0.07).<br><br>CONCLUSION: Conbercept demonstrated superior efficacy in treating wAMD compared to triamcinolone acetonide, with a lower incidence of adverse reactions. However, the current meta-analysis included a limited number of studies, with only two studies evaluating best-corrected visual acuity (BCVA). Further high-quality randomized controlled trials (RCTs) are warranted to validate these findings.},
}
@article {pmid39522752,
year = {2025},
author = {Reiter, GS and Lachinov, D and Bühl, W and Weigert, G and Grechenig, C and Mai, J and Bogunović, H and Schmidt-Erfurth, U},
title = {A Novel Management Challenge in Age-Related Macular Degeneration: Artificial Intelligence and Expert Prediction of Geographic Atrophy.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {5},
pages = {421-430},
doi = {10.1016/j.oret.2024.10.029},
pmid = {39522752},
issn = {2468-6530},
mesh = {Humans ; *Geographic Atrophy/diagnosis/etiology ; Prospective Studies ; *Artificial Intelligence ; Male ; *Tomography, Optical Coherence/methods ; Female ; Aged ; Disease Progression ; *Fluorescein Angiography/methods ; *Macular Degeneration/complications/diagnosis ; *Visual Acuity ; Fundus Oculi ; Follow-Up Studies ; *Disease Management ; Aged, 80 and over ; Deep Learning ; Algorithms ; Middle Aged ; },
abstract = {PURPOSE: The progression of geographic atrophy (GA) secondary to age-related macular degeneration is highly variable among individuals. Prediction of the progression is critical to identify patients who will benefit most from the first treatments currently approved. The aim of this study was to investigate the value and difference in predictive power between ophthalmologists and artificial intelligence (AI) in reliably assessing individual speed of GA progression.<br><br>DESIGN: Prospective, expert and AI comparison study.<br><br>PARTICIPANTS: Eyes with natural progression of GA from a prospective study (NCT02503332).<br><br>METHODS: Ophthalmologists predicted yearly growth speed of GA as well as selected the potentially faster-growing lesions from 2 eyes based on fundus autofluorescence (FAF), near-infrared reflectance (NIR), and OCT. A deep learning algorithm predicted progression solely on the baseline OCT (Spectralis, Heidelberg Engineering).<br><br>MAIN OUTCOME MEASURES: Accuracy, weighted &#x3ba;, and concordance index (c-index) between the prediction made by ophthalmology specialists, ophthalmology residents, and the AI algorithm.<br><br>RESULTS: A total of 134 eyes of 134 patients from a phase II clinical trial were included; among them, 53 were from the sham arm, and 81 were from untreated fellow eyes. Four ophthalmologists performed 2880 gradings. Human experts reached an accuracy of 0.37, 0.43, and 0.41 and a &#x3ba; of 0.06, 0.16, and 0.18 on FAF, NIR&#xa0;+ OCT, and FAF&#xa0;+ NIR&#xa0;+ OCT, respectively. On a pairwise comparison task, human experts achieved a c-index of 0.62, 0.59, and 0.60. Automated AI-based analysis reached an accuracy of 0.48 and &#x3ba; of 0.23 on the first task, and c-index of 0.69 on the second task solely utilizing OCT imaging.<br><br>CONCLUSIONS: Prediction of individual progression will become an important task for patient counseling, most importantly with the treatments becoming available. Human gradings improved with the availability of OCT. However, automated AI performed better than ophthalmologists in several comparisons. Artificial intelligence-supported decisions improve clinical precision, access to timely care for the community, and socioeconomic feasibility in the management of the leading cause of irreversible vision loss.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid39522737,
year = {2025},
author = {Rizzo, C and Savastano, MC and Kilian, R and Marchini, G and Rizzo, S},
title = {Structural en face optical coherence tomography in neovascular and nonneovascularage-related macular degeneration: Use and utility in clinical practice.},
journal = {Survey of ophthalmology},
volume = {70},
number = {4},
pages = {725-733},
doi = {10.1016/j.survophthal.2024.11.003},
pmid = {39522737},
issn = {1879-3304},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis ; *Choroidal Neovascularization/diagnosis ; Retinal Pigment Epithelium/pathology ; *Macular Degeneration/diagnosis ; Fluorescein Angiography ; Geographic Atrophy/diagnosis ; Choroid/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness and visual impairment worldwide. Structural en face optical coherence tomography (OCT) is an innovative imaging technology that has recently attracted interest because of its potential for assessing AMD features. We conducted a comprehensive review of its application in AMD. In neovascular AMD, structural en face OCT can detect exudative activity, monitor the neovascularization area, study the choroid in polypoidal choroidal vasculopathy, and visualize neovascular membranes in pigment epithelial detachments. Moreover, in nonneovascular AMD, this study provides details on geographic atrophy and drusen, the identification of intraretinal retinal pigment epithelium migration, and the detection of different patterns of outer retinal tubulations. Our study revealed that structural en face OCT can provide relevant information on patients with AMD.},
}
@article {pmid39522582,
year = {2025},
author = {Holekamp, NM},
title = {Home Optical Coherence Tomography and Sustained Delivery Approaches: A Perfect Marriage.},
journal = {American journal of ophthalmology},
volume = {277},
number = {},
pages = {497-503},
doi = {10.1016/j.ajo.2024.10.031},
pmid = {39522582},
issn = {1879-1891},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Drug Delivery Systems ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/administration &amp; dosage ; Delayed-Action Preparations ; },
abstract = {PURPOSE: To provide a perspective on the management of patients with neovascular age-related macular degeneration (nAMD) using a combination of sustained drug delivery strategies and remote monitoring technology.<br><br>DESIGN: Evidence-based perspective.<br><br>METHODS: Review of the literature and experience of the author.<br><br>RESULTS: There are currently many ongoing research efforts in the retina field directed at both safe, effective sustained drug delivery and validated remote monitoring. At present, the port delivery system with ranibizumab and the Home OCT are approved by the U.S. Food and Drug Administration and available for use by clinicians. A review of available data and a case example demonstrate the potential for these combined technologies to reduce both the injection burden and the monitoring burden currently experienced by patients with nAMD. Other sustained drug delivery strategies such as tyrosine kinase inhibitor delivery systems and viral vector-mediated anti-vascular endothelial growth factor intraocular biofactory models are not yet approved for clinical use. Early experience with these technologies in clinical trials foretell the potential advantages and possible limitations of remote monitoring with a variety of sustained delivery approaches.<br><br>CONCLUSION: The combined use of sustained drug delivery and validated remote monitoring portends a significant change in the current nAMD treatment landscape and has the potential to reduce the injection and monitoring burden faced by patients while optimizing patient outcomes.},
}
@article {pmid39521855,
year = {2024},
author = {Yang, Y and Su, S and Chen, J and Yang, X and Zhang, S and Sang, A},
title = {The perspective of ceRNA regulation of circadian rhythm on choroidal neovascularization.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {27359},
pmid = {39521855},
issn = {2045-2322},
support = {134422631103//Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province/ ; 134422631103//Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province/ ; 23ZH313//Research and Development of New Technologies and Systems for Low Vision Rehabilitation/ ; },
mesh = {*Choroidal Neovascularization/genetics/metabolism/pathology ; Animals ; Mice ; *Circadian Rhythm/genetics ; Male ; *Mice, Inbred C57BL ; Gene Regulatory Networks ; Disease Models, Animal ; Gene Expression Regulation ; RNA, Messenger/genetics/metabolism ; Gene Expression Profiling ; Transcriptome ; RNA, Competitive Endogenous ; },
abstract = {Abnormal growth of blood vessels (choroidal neovascularization) can lead to age-related macular degeneration (AMD) and eventually cause vision loss due to detachment of the retinal pigmented epithelium. This indicates that choroidal neovascularization is important for the treatment of AMD. The circadian clock in the mammalian retina is responsible for controlling various functions of the retina, enabling it to adjust to changes in light and darkness. Recent studies have revealed a potential connection between the circadian clock and eye diseases, although a cause-and-effect relationship has not been definitively established. C57BL/6J male mice (aged 6 weeks) were randomly divided into two groups (Control group: 9:00-21:00 light period (300 lx); Jet lag group: 8-hour phase advance once every 4 days). A laser-induced CNV model was created after 2 weeks of feeding in a controlled or jet-lagged environment. Then, full transcriptome sequencing was performed. The pathways regulated by differentially expressed mRNAs were identified by GO analysis and GSEA. Further protein networks were constructed with the STRING database and Cytoscape software. WGCNA was used to further explore the co-expression modules of these differential genes and the correlation between these differential genes and phenotypes. ceRNA networks were constructed with miRanda and TargetScan. The pathways associated with the overlapping differentially expressed mRNAs in the ceRNA network were identified, and the hub genes were validated by qPCR. A total of 661 important DEGs, 31 differentially expressed miRNAs, 106 differentially expressed lncRNAs and 87 differentially expressed circRNAs were identified. GO and GSEA showed that the upregulated DEGs were mainly involved in reproductive structure development and reproductive system development. The STRING database and Cytoscape were used to determine the protein interaction relationships of these DEGs. WGCNA divided the expression of these genes into several modules and screened the hub genes of each module separately. Furthermore, a ceRNA network was constructed. GO analysis and GSEA showed that these target DEmRNAs mainly function in wound healing, cell spreading, epiboly involved in wound healing, epiboly, and morphogenesis of an epithelial sheet. Finally, ten key genes were identified, and their expression patterns were confirmed by real-time qPCR. In this study, we investigated the regulatory mechanism of ceRNAs in choroidal neovascularization according to different light-dark cycles in the eyeball.},
}
@article {pmid39519580,
year = {2024},
author = {Qu, S and Zhu, Y and Pfeiffer, N and Grus, FH},
title = {Serum Iron Status and Retinal Degenerative Diseases: A Mendelian Randomization Study on AMD, RP, and DR.},
journal = {Nutrients},
volume = {16},
number = {21},
pages = {},
pmid = {39519580},
issn = {2072-6643},
support = {202108080132//China Scholarship Council/ ; },
mesh = {*Mendelian Randomization Analysis ; Humans ; *Iron/blood ; *Genome-Wide Association Study ; *Macular Degeneration/blood/genetics/epidemiology ; *Retinitis Pigmentosa/genetics/blood ; *Diabetic Retinopathy/blood/genetics/epidemiology ; Biomarkers/blood ; Polymorphism, Single Nucleotide ; Transferrin/analysis/metabolism ; Ferritins/blood ; },
abstract = {Background: Observational studies have noted that patients with certain retinal degenerative diseases exhibit iron disturbances in the retina or vitreous compared to healthy controls. However, the connection between serum iron status and these diseases remains unclear. This study aims to explore the potential causal relationship between serum iron status biomarkers and the development of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between serum iron status and several retinal degenerative diseases. Genome-wide association study (GWAS) summary-level data were extracted from public GWAS databases. Inverse-variance weighting (IVW), MR-Egger regressions, Simple model, Weighted median, and Weight mode were used as MR methods. Sensitivity analysis was conducted to confirm the robustness of the results by examining horizontal pleiotropy and heterogeneity through MR-Egger intercept and leave-one-out analysis. Results: The MR analysis revealed causal relationships between genetically predicted serum iron status biomarkers and various retinal diseases. Transferrin was positively associated with the odds of AMD (whether dry or wet) (OR = 1.167, 95% CI = 1.045-1.304, p = 0.006) and wet AMD (OR = 1.194, 95% CI = 1.018-1.402, p = 0.030). Ferritin was negatively associated with the odds of wet AMD (OR = 0.555, 95% CI = 0.333-0.927, p = 0.024). Serum iron (OR = 0.508, 95% CI = 0.260-0.993, p = 0.048) and transferrin saturation (OR = 0.508, 95% CI = 0.260-0.993, p = 0.048) were negatively associated with the odds of RP. Conclusions: These findings provide evidence supporting a potential causal relationship between serum iron status and various retinal degenerative diseases, highlighting a direction for future research into the underlying mechanisms of these diseases.},
}
@article {pmid39519401,
year = {2024},
author = {Srejovic, JV and Muric, MD and Jakovljevic, VL and Srejovic, IM and Sreckovic, SB and Petrovic, NT and Todorovic, DZ and Bolevich, SB and Sarenac Vulovic, TS},
title = {Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress.},
journal = {International journal of molecular sciences},
volume = {25},
number = {21},
pages = {},
pmid = {39519401},
issn = {1422-0067},
support = {JP 01/24//Faculty of Medical Sciences, University of Kragujevac/ ; },
mesh = {Humans ; *Oxidative Stress ; *Inflammation/metabolism/pathology ; Animals ; *Signal Transduction ; Retinal Diseases/metabolism/pathology/etiology ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {Retinal vascular diseases encompass several retinal disorders, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and retinal vascular occlusion; these disorders are classified as similar groups of disorders due to impaired retinal vascularization. The aim of this review is to address the main signaling pathways involved in the pathogenesis of retinal vascular diseases and to identify crucial molecules and the importance of their interactions. Vascular endothelial growth factor (VEGF) is recognized as a crucial and central molecule in abnormal neovascularization and a key phenomenon in retinal vascular occlusion; thus, anti-VEGF therapy is now the most successful form of treatment for these disorders. Interaction between angiopoietin 2 and the Tie2 receptor results in aberrant Tie2 signaling, resulting in loss of pericytes, neovascularization, and inflammation. Notch signaling and hypoxia-inducible factors in ischemic conditions induce pathological neovascularization and disruption of the blood-retina barrier. An increase in the pro-inflammatory cytokines-TNF-α, IL-1β, and IL-6-and activation of microglia create a persistent inflammatory milieu that promotes breakage of the blood-retinal barrier and neovascularization. Toll-like receptor signaling and nuclear factor-kappa B are important factors in the dysregulation of the immune response in retinal vascular diseases. Increased production of reactive oxygen species and oxidative damage follow inflammation and together create a vicious cycle because each factor amplifies the other. Understanding the complex interplay among various signaling pathways, signaling cascades, and molecules enables the development of new and more successful therapeutic options.},
}
@article {pmid39518966,
year = {2024},
author = {Hu, RY and Qi, SM and Wang, YJ and Li, WL and Zou, WC and Wang, Z and Ren, S and Li, W},
title = {Ginsenoside Rg3 Improved Age-Related Macular Degeneration Through Inhibiting ROS-Mediated Mitochondrion-Dependent Apoptosis In Vivo and In Vitro.},
journal = {International journal of molecular sciences},
volume = {25},
number = {21},
pages = {},
pmid = {39518966},
issn = {1422-0067},
support = {No. 82104465//the National Natural Science Foundation of China/ ; 2023YFD1601600//National Key Research and Development Program/ ; No. 2018B26//the Bethune Plan Research Project of Jilin University/ ; },
mesh = {*Ginsenosides/pharmacology ; Animals ; *Apoptosis/drug effects ; *Macular Degeneration/metabolism/drug therapy/pathology ; *Mitochondria/metabolism/drug effects ; *Reactive Oxygen Species/metabolism ; Mice ; *Membrane Potential, Mitochondrial/drug effects ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Iodates ; Disease Models, Animal ; Mice, Inbred C57BL ; Humans ; Cell Line ; Male ; Retina/metabolism/drug effects/pathology ; },
abstract = {Age-related macular degeneration (AMD) is marked by a progressive loss of central vision and is the third leading cause of irreversible blindness worldwide. The exact mechanisms driving the progression of this macular degenerative condition remain elusive, and as of now, there are no available preventative measures for dry AMD. According to ancient records, ginseng affects the eyes by brightening them and enhancing wisdom. Modern pharmacological research shows that the active ingredients in ginseng, ginsenosides, may be used to prevent or improve eye diseases that threaten vision. Some articles have reported that ginsenoside Rg3 can treat diabetic retinopathy in mice, but no reports exist on its effects and mechanisms in AMD. Therefore, the role and mechanism of ginsenoside Rg3 in AMD warrant further study. This study aims to investigate the effects of Rg3 on AMD and its underlying molecular mechanisms. We established a mouse model of AMD to examine the impact of ginsenoside Rg3 on NaIO3-induced apoptosis in the retina and to explore the related intrinsic mechanisms. The in vivo results indicated that ginsenoside Rg3 prevents NaIO3-induced apoptosis in retinal pigment epithelial cells by inhibiting reactive oxygen species production and preventing the reduction in mitochondrial membrane potential. Additionally, we assessed the levels of protein expression within the apoptosis pathway. Ginsenoside Rg3 decreased the expression of Bax, cleaved caspase-3, and cleaved caspase-9 proteins. Additionally, it increased the expression of Bcl-2 by decreasing P-JNK levels. Moreover, our in vivo results showed that ginsenoside Rg3 enhanced retinal structure, increased the relative thickness of the retina, and decreased the extent of disorganization in both the inner and outer nuclear layers. Ginsenoside Rg3 may safeguard the retina against NaIO3-induced cell apoptosis by attenuating reactive-oxygen-species-mediated mitochondrial dysfunction, in which the JNK signaling pathway is also involved. These findings suggest that ginsenoside Rg3 has the potential to prevent or attenuate the progression of AMD and other retinal pathologies associated with NaIO3-mediated apoptosis.},
}
@article {pmid39518910,
year = {2024},
author = {Xiao, JF and Luo, W and Mani, A and Barba, H and Solanki, A and Droho, S and Lavine, JA and Skondra, D},
title = {Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration.},
journal = {International journal of molecular sciences},
volume = {25},
number = {21},
pages = {},
pmid = {39518910},
issn = {1422-0067},
support = {R01 EY034486/EY/NEI NIH HHS/United States ; M2018042//BrightFocus Foundation/ ; NA//Thome Memorial Foundation Award/ ; NA//Institute for Translational Medicine/ ; K08 EY030923/NH/NIH HHS/United States ; NA//The University of Chicago Women's Board/ ; FP067271-01-PR//Illinois Society for the Prevention of Blindness/ ; R01 EY034486/NH/NIH HHS/United States ; NA//FORE-I Foundation/ ; NA//Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration/ ; K08 EY030923/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Metformin/pharmacology/administration &amp; dosage/therapeutic use ; *Choroidal Neovascularization/etiology/prevention &amp; control/pathology/drug therapy ; Mice ; *Retinal Degeneration/etiology/prevention &amp; control/pathology/drug therapy ; *Mice, Inbred C57BL ; *Intravitreal Injections ; Light/adverse effects ; Choroid/drug effects/pathology/metabolism ; Mice, Inbred BALB C ; Disease Models, Animal ; Retinal Pigment Epithelium/drug effects/pathology/metabolism ; Male ; Retina/pathology/drug effects/metabolism ; },
abstract = {Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents a challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration of anti-angiogenic agents are costly and of moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds of developing AMD. Studies have shown that metformin can mitigate cellular aging, neoangiogenesis, and inflammation across multiple diseases. This preclinical study assessed metformin's impact on vessel growth using choroidal explants before exploring IVT metformin's effects on laser-induced CNV and light-induced retinal degeneration in C57BL/6J and BALB/cJ mice, respectively. Metformin reduced new vessel growth in choroidal explants in a dose-dependent relationship. Following laser induction, IVT metformin suppressed CNV and decreased peripheral infiltration of IBA1[+] macrophages/microglia. Furthermore, IVT metformin protected against retinal thinning in response to light-induced degeneration. IVT metformin downregulated genes in the choroid and retinal pigment epithelium which are associated with angiogenesis and inflammation, two key processes that drive nAMD progression. These findings underscore metformin's capacity as an anti-angiogenic and neuroprotective agent, demonstrating this drug's potential as an accessible option to help manage nAMD.},
}
@article {pmid39518363,
year = {2024},
author = {Bell, J and Whitney, J and Cetin, H and Le, T and Cardwell, N and Srivasatava, SK and Ehlers, JP},
title = {Validation of Inter-Reader Agreement/Consistency for Quantification of Ellipsoid Zone Integrity and Sub-RPE Compartmental Features Across Retinal Diseases.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {21},
pages = {},
pmid = {39518363},
issn = {2075-4418},
support = {N/A - Only Editoorial/writing support//Stealth BioTherapeutics (United States)/ ; },
abstract = {BACKGROUND: An unmet need exists when clinically assessing retinal and layer-based features of retinal diseases. Therefore, quantification of retinal-layer-thicknesses/fluid volumes using deep-learning-augmented platforms to reproduce human-obtained clinical measurements is needed.<br><br>METHODS: In this analysis, 210 spectral-domain optical coherence tomography (SD-OCT) scans (30 without pathology, 60 dry age-related macular degeneration [AMD], 60 wet AMD, and 60 diabetic macular edema [total 23,625 B-scans]) were included. A fully automated segmentation platform segmented four retinal layers for compartmental assessment (internal limiting membrane, ellipsoid zone [EZ], retinal pigment epithelium [RPE], and Bruch's membrane). Two certified OCT readers independently completed manual segmentation and B-scan level validation of automated segmentation, with segmentation correction when needed (semi-automated). Certified reader metrics were compared to gold standard metrics using intraclass correlation coefficients (ICCs) to assess overall agreement. Across different diseases, several metrics generated from automated segmentations approached or matched human readers performance.<br><br>RESULTS: Absolute ICCs for retinal mean thickness measurements showed excellent agreement (range 0.980-0.999) across four cohorts. EZ-RPE thickness values and sub-RPE compartment ICCs demonstrated excellent agreement (ranges of 0.953-0.987 and 0.944-0.997, respectively) for full dataset, dry-AMD, and wet-AMD cohorts.<br><br>CONCLUSIONS: Analyses demonstrated high reliability and consistency of segmentation of outer retinal compartmental features using a completely human/manual approach or a semi-automated approach to segmentation. These results support the critical role that measuring features, such as photoreceptor preservation through EZ integrity, in future clinical trials may optimize clinical care.},
}
@article {pmid39515456,
year = {2025},
author = {AlAshwal, SM and Yassin, SH and Kalaw, FGP and Borooah, S},
title = {PRPH2-ASSOCIATED RETINAL DISEASES: A SYSTEMATIC REVIEW OF PHENOTYPIC FINDINGS.},
journal = {American journal of ophthalmology},
volume = {271},
number = {},
pages = {7-30},
doi = {10.1016/j.ajo.2024.10.025},
pmid = {39515456},
issn = {1879-1891},
mesh = {Humans ; Phenotype ; Tomography, Optical Coherence ; Retinal Pigment Epithelium/pathology ; *Peripherins/genetics/metabolism ; Fluorescein Angiography ; *Retinal Diseases/genetics/diagnosis ; *Mutation ; },
abstract = {PURPOSE: PRPH2-associated retinal diseases (PARD) result from pathogenic PRPH2 variants, primarily affecting photoreceptor outer segments and retinal pigment epithelium. The focus of this article is to review and discuss the phenotyping of PARD subtypes.<br><br>DESIGN: A systematic review.<br><br>METHODS: The review followed PRISMA 2020 guidelines with searches on PubMed, Medline, Web of Science, Google Scholar, and Cochrane Library. Eligible studies were those which discussed molecularly confirmed PARD or described associated diseases such as butterfly pattern dystrophy.<br><br>INCLUSION: cross-sectional, cohort, case-control studies, book chapters.<br><br>EXCLUSION: non-English, conference papers, non-peer-reviewed, or non-full text articles.<br><br>RESULTS: PARD is responsible for 25% of pattern dystrophy and up to 5% of inherited retinal dystrophies. There is clear evidence of phenotypic variability between individuals carrying the same pathogenic variant. Fundus autofluorescence, fluorescein angiography, optical coherence tomography, while in research adaptive optics reveal detailed phenotypic characteristics, notably in retinal pigment epithelium changes and photoreceptor disruption. The phenotypic of PARD variability presents diagnostic challenges, with phenotypic features often overlapping with other retinal diseases including age-related macular degeneration, Stargardt disease, and retinitis pigmentosa.<br><br>CONCLUSIONS: This review emphasizes revising diagnostic criteria by incorporating more recent imaging techniques and confirming diagnosis with the use of genetic testing. Understanding phenotypic diversity and intrafamilial variability in PARD is crucial for developing new treatments and for patient prognosis and future research should focus on larger cohorts studying genotype-phenotype correlations.},
}
@article {pmid39513868,
year = {2024},
author = {Bhattacharya, S and Yang, TS and Nabit, BP and Krystofiak, ES and Rex, TS and Chaum, E},
title = {Prominin-1 Knockdown Causes RPE Degeneration in a Mouse Model.},
journal = {Cells},
volume = {13},
number = {21},
pages = {},
pmid = {39513868},
issn = {2073-4409},
support = {S10 OD034315/OD/NIH HHS/United States ; P30CA068485, S10OD023475-01A1, S10 OD016355, IS1BX003154, CA68485, DK20593, DK58404, DK59637, EY08126, and 1S100D034315-01.//International Retina Research Foundation, the Potocsnak family gift to the Vanderbilt Eye Institute, the Margy Ann and J Donald M Gass Chair endowment, and an unrestricted departmental research grant from Research to Prevent Blindness, Inc (New York, NY)./ ; },
mesh = {*Retinal Pigment Epithelium/cytology/pathology ; *Geographic Atrophy/pathology ; Disease Models, Animal ; *AC133 Antigen/analysis/genetics/metabolism ; Photoreceptor Cells, Vertebrate/metabolism/pathology ; Microscopy, Immunoelectron ; Mice, Inbred C57BL ; Single-Cell Gene Expression Analysis ; Humans ; Male ; Female ; Animals ; Mice ; Gene Knockdown Techniques ; Mice, Transgenic ; Homeostasis ; },
abstract = {There are currently no effective treatments for retinal pigment epithelial (RPE) cell loss in atrophic AMD (aAMD). However, our research on Prominin-1 (Prom1), a known structural protein in photoreceptors (PRs), has revealed its distinct role in RPE and offers promising insights. While pathogenic Prom1 mutations have been linked to macular diseases with RPE atrophy, the broader physiological impact of dysfunctional Prom1 in RPE loss is unclear. We have shown that Prom1 plays a crucial role in regulating autophagy and cellular homeostasis in human and mouse RPE (mRPE) cells in vitro. Nevertheless, a comprehensive understanding of its in vivo expression and function in mRPE remains to be elucidated. To characterize Prom1 expression in RPE in situ, we used RNAscope assays and immunogold electron microscopy (EM). Our use of chromogenic and fluorescent RNAscope assays in albino and C57BL/6J mouse retinal sections has revealed Prom1 mRNA expression in perinuclear regions in mRPE in situ. Immunogold EM imaging showed Prom1 expression in RPE cytoplasm and mitochondria. To confirm Prom1 expression in RPE, we interrogated human RPE single-cell RNA-sequencing datasets using an online resource, Spectacle. Our analysis showed Prom1 expression in human RPE. To investigate Prom1's function in RPE homeostasis, we performed RPE-specific Prom1 knockdown (KD) using subretinal injections of AAV2/1.CMV.saCas9.U6.Prom1gRNA in male and female mice. Our data show that RPE-specific Prom1-KD in vivo resulted in abnormal RPE morphology, subretinal fluid accumulation, and secondary PR loss. These changes were associated with patchy RPE cell death and reduced a-wave amplitude, indicating retinal degeneration. Our findings underscore the central role of Prom1 in cell-autonomous mRPE homeostasis. The implications of Prom1-KD causing aAMD-like RPE defects and retinal degeneration in a mouse model are significant and could lead to novel treatments for aAMD.},
}
@article {pmid39512482,
year = {2024},
author = {Narendran, N and Bailey, C and Downey, L and Gale, R and Kotagiri, A and Pearce, I and Rennie, CA and Sivaprasad, S and Talks, J and Morgan-Warren, P and Napier, J and O'Neil, C and Seeborne, T},
title = {Expert Panel Consensus for Optimizing Outcomes in Neovascular Age-Related Macular Degeneration in the Context of Suboptimal Response to a Biosimilar: The Role of Aflibercept.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3133-3142},
pmid = {39512482},
issn = {1177-5467},
abstract = {PURPOSE: The inclusion of ranibizumab biosimilars into National Health Service England commissioning recommendations published in 2022 created a need for expert guidance to optimize treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) who otherwise may not have received first-line ranibizumab. This article provides a consensus treatment pathway supporting timely identification and management of a suboptimal response to these therapies, thereby aiming to facilitate clinically meaningful outcomes and efficient management of service capacity under specific circumstances where ranibizumab biosimilars may be initiated as a first-line treatment.<br><br>METHODS: Two structured round-table meetings of UK medical retina specialists were held in person and virtually on September 22 and November 3, 2022, respectively. These meetings were organized and funded by Bayer.<br><br>RESULTS: The panel provided guidance on the implementation of an early treatment optimization pathway in cases where ranibizumab biosimilars are used as a first-line treatment, including recommendations on patient suitability and capacity requirements, and criteria for identification and strategies for management of a suboptimal response. The panel discussed the role of aflibercept treatment and its potential benefits and outlined recommendations on switching ranibizumab biosimilar suboptimal responders to an aflibercept treat-and-extend regimen, where appropriate.<br><br>CONCLUSION: Developed by a retinal expert panel, this early treatment optimization pathway provides guidance to facilitate optimal long-term patient outcomes while addressing capacity and resourcing constraints in circumstances of first-line ranibizumab biosimilar use for nAMD, including how aflibercept may be used in cases with a suboptimal response. Therefore, this fills an important gap in guidance on navigating the new treatment landscape.},
}
@article {pmid39511313,
year = {2024},
author = {Lee, JH and Yu, HG and Yoon, CK},
title = {A pilot study : retinal sensitivity change in neovascular age-related macular degeneration patients with better baseline visual acuity.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {27035},
pmid = {39511313},
issn = {2045-2322},
mesh = {Humans ; *Visual Acuity ; Female ; Male ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Pilot Projects ; Aged ; *Tomography, Optical Coherence ; *Recombinant Fusion Proteins/therapeutic use ; *Retina/diagnostic imaging/physiopathology/drug effects/pathology ; Aged, 80 and over ; Macular Degeneration/drug therapy/physiopathology ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {This study evaluated changes in retinal sensitivity (RS) during aflibercept treatment in neovascular age-related macular degeneration (nAMD) patients with good vision. Treatment-naive nAMD patients with visual acuity better than 20/40 were treated with an aflibercept loading regiment, and RS was measured using the MAIA microperimetry device. The study examined RS differences based on visit, region, adjacent local pathology, outer retinal changes and optical coherence tomography angiography (OCTA) data were investigated. Twelve patients completed the protocol. Mean RS improved from 17.9 (3.9) µm at baseline to 20.4 (4.7) µm at final visit, while best-corrected visual acuity (BCVA) did not change. (P = 0.041) RS at baseline is worst in the presence of intraretinal fluid (IRF) and improved after treatment for all retinal pathologies except IRF. RS improvement occurred even with initial outer retinal damage. A Linear mixed model showed subretinal hyperreflective material, baseline IRF height, outer retinal integrity, fibrovascular pigment epithelial detachment height, and local choroidal vascular index as factors associated with RS. In conclusion, RS improved with aflibercept treatment in nAMD eyes with good initial visual acuity, despite no change in BCVA, except when IRF was present.},
}
@article {pmid39511248,
year = {2024},
author = {Heinke, A and Zhang, H and Broniarek, K and Michalska-Małecka, K and Elsner, W and Galang, CMB and Deussen, DN and Warter, A and Kalaw, F and Nagel, I and Agnihotri, A and Mehta, NN and Klaas, JE and Schmelter, V and Kozak, I and Baxter, SL and Bartsch, DU and Cheng, L and An, C and Nguyen, T and Freeman, WR},
title = {Cross-instrument optical coherence tomography-angiography (OCTA)-based prediction of age-related macular degeneration (AMD) disease activity using artificial intelligence.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {27085},
pmid = {39511248},
issn = {2045-2322},
support = {5R01EY033847/GF/NIH HHS/United States ; DP5OD029610/GF/NIH HHS/United States ; OT2OD032644/GF/NIH HHS/United States ; T15 LM011271/LM/NLM NIH HHS/United States ; R01EY016323/GF/NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Cross-Sectional Studies ; *Macular Degeneration/diagnostic imaging/pathology ; *Artificial Intelligence ; Male ; Aged ; Female ; Neural Networks, Computer ; Aged, 80 and over ; Middle Aged ; },
abstract = {This study investigates the efficacy of predicting age-related macular degeneration (AMD) activity through deep neural networks (DNN) using a cross-instrument training dataset composed of Optical coherence tomography-angiography (OCTA) images from two different manufacturers. A retrospective cross-sectional study analyzed 2D vascular en-face OCTA images from Heidelberg Spectralis (1478 samples: 1102 training, 276 validation, 100 testing) and Optovue Solix (1003 samples: 754 training, 189 validation, 60 testing). OCTA scans were labeled based on clinical diagnoses and adjacent B-scan OCT fluid information, categorizing activity into normal, dry AMD, active wet AMD, and wet AMD in remission. Experiments explored cross-instrument disease classification using separate and combined datasets for training the DNN. Testing involved 100 Heidelberg and 60 Optovue samples. Training on Heidelberg data alone yielded 73% accuracy on Heidelberg images and 60% on Optovue images. Training on Optovue data alone resulted in 34% accuracy on Heidelberg and 85% on Optovue images. Combined training data from both instruments achieved 78% accuracy on Heidelberg and 76% on Optovue test sets. Results indicate that cross-instrument classifier training demonstrates high classification prediction accuracy, making cross-instrument training viable for future clinical applications. This implies that vascular morphology in OCTA can predict disease progression.},
}
@article {pmid39510906,
year = {2024},
author = {Sørensen, TL},
title = {Erratum to "Age-related macular degeneration (AMD) is a detrimental eye disease, and the most common cause of visual loss in many countries around the world" [Pharmacol. Res. 208 (2024) 107402].},
journal = {Pharmacological research},
volume = {210},
number = {},
pages = {107470},
doi = {10.1016/j.phrs.2024.107470},
pmid = {39510906},
issn = {1096-1186},
}
@article {pmid39508777,
year = {2024},
author = {Bui, B and Guymer, RH and Heriot, W and Metha, A and Luu, CD},
title = {Impairment of Neurovascular Function in Intermediate Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {11},
pages = {4},
pmid = {39508777},
issn = {2164-2591},
mesh = {Humans ; Male ; Female ; *Tomography, Optical Coherence ; Aged ; Middle Aged ; *Retinal Vessels/physiopathology/diagnostic imaging ; *Macular Degeneration/physiopathology ; Fluorescein Angiography/methods ; Choroid/blood supply/physiopathology ; Aged, 80 and over ; Retinal Drusen/physiopathology ; },
abstract = {PURPOSE: To investigate neurovascular function in eyes with age-related macular degeneration (AMD).<br><br>METHODS: Subjects with bilateral large drusen (intermediate AMD) and healthy controls &#x2265;50&#xa0;years old were recruited. The vasculature within the central 6 &#xd7; 6-mm retinal area was captured using optical coherence tomography angiography (OCTA) and segmented to return superficial plexus, deep plexus, choriocapillaris, and choroid. OCTA scans were acquired without flicker light stimulation (conventional OCTA) and during flicker light stimulation to increase retinal activity and metabolic demand (functional OCTA). Vascular area density (VAD) and the vascular reactivity index (VRI; change in VAD induced by flicker stimulation) were determined and compared between control and AMD eyes.<br><br>RESULTS: Thirty-five subjects (19 AMD cases and 16 healthy controls) participated in the study. In healthy eyes, flicker stimulation induced an increase in VAD (positive VRI, vasodilation) in the superficial plexus (P < 0.001) and deep plexus (P < 0.001). There was a trend for increased VAD in the choriocapillaris (P = 0.077), but there was no change in the choroid (P = 0.654). In AMD eyes, there was no change in VAD in response to flicker stimulation in any of the vascular layers examined (P &#x2265; 0.294). Linear mixed models confirmed that AMD was associated with a reduced VRI in the superficial plexus (P < 0.001) and deep plexus (P < 0.001).<br><br>CONCLUSIONS: Eyes with large drusen show a reduction in retinal vascular reactivity compared to healthy eyes, which suggests that there is impairment of retinal neurovascular function in intermediate AMD.<br><br>TRANSLATIONAL RELEVANCE: Functional OCTA could be used to study neurovascular function in retinal diseases.},
}
@article {pmid39508067,
year = {2024},
author = {Davidson, MH and Hsieh, A and Kastelein, JJP},
title = {Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity.},
journal = {Current opinion in lipidology},
volume = {35},
number = {6},
pages = {303-309},
pmid = {39508067},
issn = {1473-6535},
mesh = {*Cholesterol Ester Transfer Proteins/antagonists &amp; inhibitors ; Humans ; *Longevity ; Animals ; Anticholesteremic Agents/therapeutic use/pharmacology ; },
abstract = {PURPOSE OF REVIEW: To review the evidence and describe the biological plausibility for the benefits of inhibiting cholesteryl ester transfer protein (CETP) on multiple organ systems through modification of lipoprotein metabolism.<br><br>RECENT FINDINGS: Results from observational studies, Mendelian randomization analyses, and randomized clinical trials support the potential of CETP inhibition to reduce atherosclerotic cardiovascular disease (ASCVD) risk through a reduction of apolipoprotein B-containing lipoproteins. In contrast, raising high-density lipoprotein (HDL) particles, as previously hypothesized, did not contribute to ASCVD risk reduction. There is also an expanding body of evidence supporting the benefits of CETP inhibition for safeguarding against other conditions associated with aging, particularly new-onset type 2 diabetes mellitus and dementia, as well as age-related macular degeneration, septicemia, and possibly chronic kidney disease. The latter are likely mediated through improved functionality of the HDL particle, including its role on cholesterol efflux and antioxidative, anti-inflammatory, and antimicrobial activities.<br><br>SUMMARY: At present, there is robust clinical evidence to support the benefits of reducing CETP activity for ASCVD risk reduction, and plausibility exists for the promotion of longevity by reducing risks of several other conditions. An ongoing large clinical trial program of the latest potent CETP inhibitor, obicetrapib, is expected to provide further insight into CETP inhibition as a therapeutic target for these various conditions.},
}
@article {pmid39507932,
year = {2024},
author = {Soliño, M and López-Costa, JJ and Martínez, A},
title = {Editorial: Novel therapeutic strategies for retinal degeneration.},
journal = {Frontiers in ophthalmology},
volume = {4},
number = {},
pages = {1507844},
doi = {10.3389/fopht.2024.1507844},
pmid = {39507932},
issn = {2674-0826},
}
@article {pmid39507811,
year = {2024},
author = {Shamabadi, A and Asadigandomani, H and Kazemzadeh, K and Farahmand, K and Arabzadeh Bahri, R and Akhondzadeh, S},
title = {Crocus sativus (saffron) and age-related macular degeneration.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {13},
number = {3},
pages = {139-150},
pmid = {39507811},
issn = {2322-3219},
abstract = {BACKGROUND: Age-related macular degeneration (ARMD) leads to impaired vision and potential blindness. Globally, it accounts for approximately 9% of vision loss cases, and a projected 288 million individuals will be affected by 2040. Current treatments have limitations such as variable effectiveness, high costs, and potential side effects. Additionally, atrophic ARMD management remains challenging. As saffron has shown promising neuroprotective and antioxidant effects by potentially delaying disease progression, this study aims to review the mechanistic, pre-clinical, and clinical evidence of the effects, safety, and tolerability of saffron in ARMD treatment.<br><br>METHODS: The Scale for the Assessment of Narrative Review Articles was applied in this narrative review. To find relevant literature, the syntax "(saffron OR crocus) AND (retin* OR "geographic atrophy" OR "choroidal neovascular*" OR "macular degeneration")" was searched in PubMed/MEDLINE. Pre-clinical and clinical original investigations of the effects of saffron in ARMD along with the eligible studies cited in their reference lists were identified and included.<br><br>RESULTS: Saffron and its active compounds, crocin and crocetin, have shown promising results in improving visual function and delaying ARMD progression. Several clinical studies have found that daily supplementation with 20-50 mg of saffron or 5-15 mg of crocin for 3-12 months significantly improved best-corrected visual acuity, contrast sensitivity, and retinal function as measured by electroretinogram and microperimetry, with benefits observed in both dry and wet forms of ARMD. The effects were independent of genetic risk factors and maintained during the follow-up periods, suggesting the potential role of saffron as a long-term treatment option. Saffron reduces ARMD progression via anti-angiogenic, neuroprotective, and antioxidant mechanisms. Moreover, saffron is safe and well tolerated.<br><br>CONCLUSIONS: Although further research is needed to confirm long-term safety and efficacy, current evidence supports the use of saffron or crocin supplements as a safe and tolerable adjunct therapy for ARMD management.},
}
@article {pmid39507809,
year = {2024},
author = {Kayabasi, M and Koksaldi, S and Saatci, AO},
title = {Intraretinal hyperreflective line: potential biomarker in various retinal disorders.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {13},
number = {3},
pages = {129-138},
pmid = {39507809},
issn = {2322-3219},
abstract = {BACKGROUND: The intraretinal hyperreflective line (IHL) is a novel posterior segment finding demonstrable using careful optical coherence tomography (OCT) examination. It likely indicates a reaction against photoreceptor, Muller cell, and/or retinal pigment epithelial damage. This study analyzed the spectral-domain OCT characteristics of IHLs to disclose their presence in various retinal conditions.<br><br>METHODS: A retrospective review of the charted and imaging records of participants with IHL was conducted at Dokuz Eylul University Department of Ophthalmology between January 2019 and August 2023. The inclusion criterion was the detection of an IHL on good-quality B-scan spectral-domain OCT. An IHL was defined as a vertical line extending from the ellipsoid zone band (or lower) through the outer nuclear layer to the internal limiting membrane in the central fovea. Associated retinal conditions were recorded as potential causative factors for the presence of IHL.<br><br>RESULTS: IHL was observed on spectral-domain OCT in 40 eyes of 38 participants with several retinal diseases assessment. Fourteen eyes (35%) underwent vitreoretinal surgery pre-IHL detection (12 were operated for full-thickness macular hole [FTMH], one for epiretinal membrane [ERM], and one for rhegmatogenous retinal detachment). In six eyes (15%) a microhole coexisted. Four eyes (10%) had a concurrent lamellar macular hole. The IHL preceded the occurrence of FTMH in three eyes (7.5%), and diabetic macular edema and type 2 idiopathic macular telangiectasia (MacTel-2) were present in three eyes (7.5%) each. The remaining conditions included vitreomacular traction (VMT), nonarteritic anterior ischemic optic neuropathy with central retinal artery occlusion, commotio retinae, exudative age-related macular degeneration, ERM, non-infectious idiopathic posterior uveitis, and Coats' disease, each affecting one eye (2.5%). Of the two participants with bilateral involvement, one was diagnosed with MacTel-2 and the other had IHL with VMT in the right eye that was detected post-vitreoretinal surgery for FTMH in the left eye.<br><br>CONCLUSIONS: Although IHLs are mostly identified in eyes with vitreomacular surface diseases, clinicians may encounter IHLs in other types of retinal pathology. Further large-scale, multicenter, long-term studies on the presence of IHLs in OCT imaging are required to provide more substantial insight on this biomarker.},
}
@article {pmid39506000,
year = {2024},
author = {Gao, X and Liu, C and Yin, L and Wang, A and Li, J and Gao, Z},
title = {Machine learning model for age-related macular degeneration based on heavy metals: The National Health and Nutrition Examination Survey 2005 to 2008.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {26913},
pmid = {39506000},
issn = {2045-2322},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Age Factors ; Cadmium/toxicity/urine ; Cross-Sectional Studies ; Early Diagnosis ; Environmental Exposure/adverse effects/statistics &amp; numerical data ; Fundus Oculi ; *Machine Learning ; *Macular Degeneration/diagnosis/epidemiology/etiology/urine ; *Metals, Heavy/toxicity/urine ; Nutrition Surveys/statistics &amp; numerical data ; Predictive Value of Tests ; *Risk Assessment/methods ; Risk Factors ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in older people in developed countries. It has been suggested that heavy metal exposure may be associated with the development of AMD, but most studies have focused on the effects of a single metal with traditional methods. In this study, we analyzed the relationship between 13 urinary heavy metal concentrations and AMD using NHANES data between 2005 and 2008. We constructed and compared 11 machine learning models to identify the best model for predicting AMD risk. We further interpreted the models by Permutation Feature Importance (PFI), Partial Dependence Plot (PDP) analysis, and SHapley Additive exPlanations (SHAP) analysis. 216 AMD patients out of 2380 participants. The random forest (RF) model performed optimally in predicting the risk of AMD, with an AUC value of 0.970. PFI analyses revealed that age and urinary cadmium (Cd) were the main factors influencing the risk of AMD. SHAP analyses further confirmed the significance of Cd concentration in predicting the risk of AMD, and we revealed a significant interaction with significant interaction of race. Our study firstly explored the relationship between heavy metal exposure levels and AMD based on machine learning techniques, found that urinary Cd concentration had the greatest impact on AMD, and revealed the superior predictive performance of machine learning methods. Furthermore, our study provided a new perspective for early screening and intervention of AMD.},
}
@article {pmid39505382,
year = {2024},
author = {Yang, CC and Ma, Y and Jiang, Q and Xue, JS},
title = {[Research progress on the pathogenesis of PM2.5 in ophthalmic diseases].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {60},
number = {11},
pages = {943-949},
doi = {10.3760/cma.j.cn112142-20231220-00296},
pmid = {39505382},
issn = {0412-4081},
support = {82070983//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Particulate Matter/adverse effects ; *Eye Diseases/etiology ; Air Pollutants/adverse effects ; Glaucoma/etiology ; Dry Eye Syndromes/etiology ; Cataract/etiology ; Meibomian Glands ; },
abstract = {PM2.5 is a fine particulate matter with an aerodynamic equivalent diameter of less than or equal to 2.5 μm, and it is the primary pollutant that causes haze. In recent years, numerous research results have shown that PM2.5 is associated with various ophthalmic diseases and its pathogenic mechanism is complex. It can disrupt the homeostasis of the tear film and the function of the meibomian glands, leading to dry eye; increase the risk of allergic and other types of conjunctivitis; may cause blepharitis; affect the homeostasis of the corneal epithelium and promote the development of keratopathy; the correlation with cataract is controversial; it is related to the risk of glaucoma; it is associated with age-related macular degeneration; it may also indirectly promote diabetic retinopathy. Prevention and control measures include controlling the level of PM2.5, strengthening publicity and screening, reducing going out and wearing goggles, etc. PM2.5 is closely related to ophthalmic diseases, but its specific pathogenic mechanism still requires more research to explore.},
}
@article {pmid39504678,
year = {2025},
author = {Hayek, G and Reglodi, D and Goetz, C and Perone, JM and Csutak, A},
title = {Ranibizumab treatment improves the reading speed of patients with neovascular age-related macular degeneration: A nonrandomized clinical trial using the Radner reading chart.},
journal = {Journal francais d'ophtalmologie},
volume = {48},
number = {1},
pages = {104350},
doi = {10.1016/j.jfo.2024.104350},
pmid = {39504678},
issn = {1773-0597},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Intravitreal Injections ; *Macular Degeneration/drug therapy/complications ; *Ranibizumab/therapeutic use/administration &amp; dosage ; *Reading ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Vision Tests/methods/instrumentation ; Visual Acuity/drug effects ; *Wet Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: Intravitreal injections with anti-vascular endothelial growth factor (VEGF) drugs can slow progression in neovascular age-related macular degeneration (nAMD). Best spectacle-corrected visual acuity (BSCVA) and/or central retinal thickness (CRT) are common barometers of efficacy of this treatment. However, BSCVA does not accurately measure reading ability, which is often severely impacted by nAMD. Since most studies on the effect of intravitreal anti-VEGF injections on reading ability in nAMD have limitations, we conducted an open-label nonrandomized non-blinded self-controlled clinical trial using Radner Charts, a standardized, validated tool for measuring reading ability.<br><br>METHODS: Patients newly diagnosed with active nAMD and scheduled to undergo induction ranibizumab treatment (monthly treatments for 3months) were recruited by convenience sampling in 2010-2013 at a university hospital. The primary outcome was change in Radner Chart-determined reading speed (maximum words/minute [wpm]) at 3months (1month post-third injection) relative to baseline. Secondary outcome measures were 3-month change in BSCVA and CRT. Treatment-induced effects on wpm, BSCVA, and CRT were determined with Wilcoxon tests. Spearman correlations between these variables were evaluated.<br><br>RESULTS: The injections significantly improved wpm (48 to 75), BSCVA (+9 letters), and CRT (357 to 224&#x3bc;m) (all P<0.0001). BSCVA, but not CRT, correlated with wpm at baseline and 3months (P=0.0004 and 0.03, respectively). BSCVA and CRT were not correlated, unless change in these variables was considered, possibly because of a non-linear relationship.<br><br>CONCLUSION: Anti-VEGF treatment significantly improved reading ability. Whether BSCVA can serve as a clinically meaningful assessment of reading ability requires further research. Baseline variables may not help to identify patients with poor reading speed responses to treatment.},
}
@article {pmid39503991,
year = {2025},
author = {Seo, N and Kuhns, S and Andrews, DA and Colbert, A and Chow, V and Liu, J},
title = {Nonclinical Similarity of the Biosimilar Candidate ABP 938 with Aflibercept Reference Product.},
journal = {Ophthalmology and therapy},
volume = {14},
number = {1},
pages = {85-101},
pmid = {39503991},
issn = {2193-8245},
abstract = {INTRODUCTION: ABP 938 is being developed as a biosimilar to Eylea[®] (aflibercept reference product [RP]), an anti-vascular endothelial growth factor (VEGF) drug used in the management of retinal diseases. Previously, a comparative analytical similarity assessment demonstrated that ABP 938 and aflibercept RP have the same amino acid sequence and exhibit similar higher-order structure and biological activity. The nonclinical studies described here were designed to assess the in vitro pharmacology and the in vivo pharmacokinetics (PK), toxicokinetics (TK), and safety profiles of ABP 938 compared to aflibercept RP.<br><br>METHODS: In vitro target-binding kinetics and affinity for VEGF-A and placental growth factor (PIGF) isoforms were evaluated using surface plasmon resonance (SPR). Effector functions were assessed by cell-based assays. PK was evaluated in a nonterminal intravitreal (IVT) ocular distribution study in rabbits. Safety was assessed in a 1-month IVT study in cynomolgus monkeys.<br><br>RESULTS: SPR results demonstrated that ABP 938 is similar to aflibercept RP in binding kinetics and affinity for VEGF-A111, VEGF-A121, VEGF-A165, VEGF-A189, PlGF-1, and PlGF-2 isoforms. No antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity was observed with ABP 938 and aflibercept RP. Results from the&#xa0;nonterminal ocular distribution study in rabbits indicated that there were no meaningful differences in the distribution kinetics between intravitreally injected ABP 938 and aflibercept RP. Additionally, there was no evidence of ocular or systemic toxicity associated with IVT administration of ABP 938 in a repeat-dose, 1-month toxicology study in cynomolgus monkeys; toxicokinetic and toxicology profiles were similar to aflibercept RP.<br><br>CONCLUSIONS: This integrated assessment of results from the in vitro pharmacology assessment and in vivo PK and TK/toxicology profiles formed the nonclinical portion of the totality of evidence demonstrating ABP&#xa0;938 is a biosimilar to aflibercept RP.},
}
@article {pmid39502824,
year = {2024},
author = {Huang, Y and Tang, T and Wang, D and Gao, Y and Zhang, M},
title = {Global, regional, and national burden of age-related macular degeneration, 1990-2019: an age-period-cohort analysis based on the Global Burden of Disease 2019 Study.},
journal = {Frontiers in public health},
volume = {12},
number = {},
pages = {1486168},
pmid = {39502824},
issn = {2296-2565},
mesh = {Humans ; *Global Burden of Disease ; *Macular Degeneration/epidemiology ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over ; Cohort Studies ; *Disability-Adjusted Life Years ; Global Health/statistics &amp; numerical data ; Adult ; Quality-Adjusted Life Years ; Cost of Illness ; },
abstract = {OBJECTIVES: This study aimed to explore the burden of disease and disparities in age-related macular degeneration (AMD) at the global, regional, and national levels from 1990 to 2019 using data from the Global Burden of Disease (GBD) 2019 study, with a particular focus on associations with age, period, and cohort.<br><br>METHODS: We derived disability-adjusted life years (DALYs) and age-standardized rates of AMD from the GBD 2019. We used an age-period-cohort (APC) model to estimate the overall annual percentage changes in DALYs (net drifts), the annual percentage changes in different age groups (local drifts), the longitudinal age profiles (longitudinal age-specific rates), and the relative risks of period and cohort (period and cohort effects) between 1990 and 2019. Further analysis was conducted by country, region, gender and sociodemographic index (SDI).<br><br>RESULTS: Globally, the number of DALYs increased from 296771.9321 (95% uncertainty interval [UI], 205462.8041-418699.8184) in 1990 to 564055.0967 (95% UI, 392930.6967-789194.6407) in 2019 (59.7% were female), while the age-standardized DALYs rates decreased from 8.29 per 100,000 (95% UI, 5.8-11.58/100,000) to 7.05 per 100,000 (95% UI, 4.92-9.84/100,000). With increasing age, the burden of AMD increased, and the DALYs rates in female was greater than that in male in all age groups. The burden of disease varied across SDI regions and countries. The top three countries in terms of the number of DALYs were China, India and Italy, accounting for 45% of the global total.<br><br>CONCLUSION: The burden of AMD varied according to SDI, country, and sex from 1990 to 2019. Due to global population growth and aging, AMD will continue to be a major public health problem in the future, and relevant health policies need to be continuously improved and optimized.},
}
@article {pmid39502309,
year = {2024},
author = {Machado, DF and Peña, SS and Alves, MC and Siqueira, GC and Pereira, LA and de Carvalho, SS and Gascon, TM and Alves, BDCA and da Veiga, GL and Fonseca, FLA and Lima, VL and Ballalai, P},
title = {Atypical Presentation of Choroidal Osteoma: Two Case Reports.},
journal = {International medical case reports journal},
volume = {17},
number = {},
pages = {891-894},
pmid = {39502309},
issn = {1179-142X},
abstract = {Choroidal osteoma is a rare, benign, osseous choristoma presenting as an orange-yellow, well-defined fundus mass. It presents unilaterally in most cases, has a predilection for the female sex, and favor a juxtapapillary location, becoming clinically manifest when it involves the macula. Almost 60% of eyes with osteoma may suffer significant visual loss. Choroidal osteomas can easily be mistaken for other conditions with similar presentations. We herein report two rare cases presentation of choroidal osteoma: a 74-year-old male with 2-year blurred vision in the right eye (RE) initially misdiagnosed with age-related macular degeneration received intravitreal injections and after a multimodal evaluation, following cataract surgery in RE, confirmed to be choroidal osteoma and a 19-year-old female with a history of choroidal hemangioma presented with blurred vision in her left eye (LE), with examination revealed an irregular orange-yellow lesion along the superotemporal arcade with serous macular detachment, later diagnosed as choroidal osteoma.},
}
@article {pmid39501348,
year = {2024},
author = {Chan, KS and Aggarwal, N and Lawson, S and Boucher, N and MacCumber, MW and Lavine, JA},
title = {Levodopa is associated with reduced development of new-onset geographic atrophy in patients with age-related macular degeneration.},
journal = {Eye and vision (London, England)},
volume = {11},
number = {1},
pages = {44},
pmid = {39501348},
issn = {2326-0254},
support = {R01 EY034486/EY/NEI NIH HHS/United States ; Unrestricted Departmental Grant//Research to Prevent Blindness/ ; Sybil B. Harrington Career Development Award for Macular Degeneration//Research to Prevent Blindness/ ; K08 EY030923/EY/NEI NIH HHS/United States ; EY030923/EY/NEI NIH HHS/United States ; EY034486/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND: Geographic atrophy (GA) is a significant cause of vision loss in patients with age-related macular degeneration (AMD). Current treatments are limited to anti-complement drugs, which have limited efficacy to delay progression with significant risk of complications. Levodopa (L-DOPA) is a byproduct of melanin synthesis that is associated with reduced development of neovascular AMD. In this study, we determined if L-DOPA was associated with a reduced likelihood of new-onset GA.<br><br>METHODS: We performed a retrospective analysis in the Vestrum Health Retina Database. We included eyes with non-neovascular AMD without GA and 1-5&#xa0;years of follow-up. Eyes were divided into two groups. Exposed to L-DOPA before or on the date of non-neovascular AMD without GA diagnosis, and eyes not exposed to L-DOPA. We extracted age, sex, AREDS2 status, dry AMD stage, smoking history, and conversion rate to GA at years 1 through 5. Propensity score matching was used to match L-DOPA and control groups. Cox proportional hazard regression, adjusting for age, sex, AMD severity, AREDS2 use, smoking status, and L-DOPA use was employed to calculate hazard ratios for new-onset GA detection.<br><br>RESULTS: We identified 112,089 control and 844 L-DOPA exposed eyes with non-neovascular AMD without GA. After propensity score matching, 2532 control and 844 L-DOPA exposed eyes remained that were well-matched for age, sex, AMD severity, AREDS2 use, and smoking status. We found that L-DOPA exposure was associated with a significantly reduced likelihood (HR&#x2009;=&#x2009;0.68, 95% CI: 0.48-0.95, P&#x2009;=&#x2009;0.025) of new-onset GA detection.<br><br>CONCLUSION: L-DOPA use was associated with reduced detection of new-onset GA.},
}
@article {pmid39500360,
year = {2024},
author = {You, L and Lin, Y and Zheng, Y and Han, Z and Zeng, L and Chen, H},
title = {The Impact of Aging on Ocular Diseases: Unveiling Complex Interactions.},
journal = {Aging and disease},
volume = {16},
number = {5},
pages = {2803-2830},
pmid = {39500360},
issn = {2152-5250},
mesh = {*Eye Diseases/etiology/pathology/physiopathology/therapy ; *Aging/pathology/physiology ; Humans ; Eye/pathology/physiopathology ; Animals ; },
abstract = {Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. Aging is an important risk factor for eye diseases. The gradual deterioration of ocular tissue structure and function with age leads to the onset and progression of ocular diseases. During aging, ocular tissues such as the lens, vitreous and retina are affected by age-related changes, such as oxidative stress and protein accumulation in the lens leading to cataract formation, and a decline in retinal pigment epithelial cell function associated with macular degeneration. This article reviews the relationships between aging and ocular diseases, takes age-related macular degeneration, age-related cataracts, glaucoma, diabetic retinal degeneration, and dry eye disease as focal points, analyses the complex interactions between aging and ocular diseases, and describes the therapeutic options and potential targets for age-related ocular diseases.},
}
@article {pmid39500350,
year = {2024},
author = {Modgil, S and Ahmed, T and Liao, YJ},
title = {Axonal Energy Crisis and Calcium Phosphate Dysregulation as Pathogenesis of Optic Disc Drusen.},
journal = {Aging and disease},
volume = {16},
number = {5},
pages = {2739-2751},
pmid = {39500350},
issn = {2152-5250},
mesh = {Humans ; *Optic Disk Drusen/metabolism/pathology/etiology ; *Calcium Phosphates/metabolism ; *Axons/metabolism/pathology ; Mitochondria/metabolism ; Animals ; Calcinosis/metabolism ; *Energy Metabolism ; Calcium/metabolism ; Hypoxia/metabolism ; },
abstract = {Soft tissue ectopic calcification is due to abnormal accumulation of calcium and phosphate outside the bone. It is the result of the failure of a complex, active, and highly regulated process - much of which is still not well understood. Some of our understanding of ectopic calcification come from studies on diseases such as atherosclerosis, aortic valve disease and kidney stone disease. In the eye, the most common causes of visual defects due to ectopic calcification include optic disc drusen (ODD) and age-related macular degeneration (AMD). In ODD, ectopic calcification occurs only in the most anterior, unmyelinated portion of optic nerve - the sole output of the eye and particularly susceptible to hypoxic and metabolic stress. In this article, we review the effects of hypoxia on mitochondrial function and calcium regulation and delineate the key processes likely involved in ectopic calcification. We propose a working hypothesis for ODD centering on the role of hypoxia-induced calcium and phosphate overload, mitochondrial dysfunction and osteogenic differentiation, leading to hydroxyapatite deposition and biomineralization.},
}
@article {pmid39499641,
year = {2024},
author = {Sharma, D and Lau, E and Qin, Y and Jee, K and Rodrigues, M and Guo, C and Dinabandhu, A and McIntyre, E and Salman, S and Hwang, Y and Moshiri, A and Semenza, GL and Montaner, S and Sodhi, A},
title = {VEGF inhibition increases expression of HIF-regulated angiogenic genes by the RPE limiting the response of wet AMD eyes to aflibercept.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {46},
pages = {e2322759121},
pmid = {39499641},
issn = {1091-6490},
support = {Sybil B. Harrington Stein Innovation Award//Research to Prevent Blindness (RPB)/ ; P30 EY001765/EY/NEI NIH HHS/United States ; TEDCO Maryland Innovation Initiative//State of Maryland (The State of Maryland)/ ; unrestricted grant//Research to Prevent Blindness (RPB)/ ; R01 EY032104/EY/NEI NIH HHS/United States ; Branna and Irving Sisenwein Professorship//Branna and Irving Sisenwein Professorship/ ; R01 EY029750/EY/NEI NIH HHS/United States ; Special Scholar Award//Research to Prevent Blindness (RPB)/ ; EY001765//HHS | NIH | National Eye Institute (NEI)/ ; C. Michael Armstrong Professorship//Armstrong Family Foundation/ ; },
mesh = {Animals ; Humans ; *Receptors, Vascular Endothelial Growth Factor/metabolism/genetics ; *Angiopoietin-Like Protein 4/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Mice ; *Recombinant Fusion Proteins ; *Choroidal Neovascularization/drug therapy/metabolism/genetics ; Wet Macular Degeneration/drug therapy/metabolism/genetics ; Angiogenesis Inhibitors/pharmacology ; Gene Expression Regulation/drug effects ; Male ; Female ; },
abstract = {Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated that expression of a second angiogenic mediator, angiopoietin-like 4 (ANGPTL4), synergizes with VEGF to promote choroidal neovascularization (CNV) in mice and correlates with reduced response to anti-VEGF therapy in patients with nvAMD. Here, we report that expression of ANGPTL4 in patients with nvAMD increases following treatment with anti-VEGF therapy and that this increase is dependent on accumulation of hypoxia-inducible factor (HIF)-1α in response to inhibition of VEGF/KDR signaling in the retinal pigment epithelium (RPE). We therefore explored HIF-1 inhibition with 32-134D, a recently developed pharmacologic HIF-inhibitor, for the treatment of nvAMD. 32-134D prevented the expression of both VEGF and ANGPTL4 and was at least as effective as aflibercept in treating CNV in mice. Moreover, by preventing the increase in HIF-1α accumulation in the RPE in response to anti-VEGF therapy, combining 32-134D with aflibercept was more effective than either drug alone for the treatment of CNV. Collectively, these results help explain why many patients with nvAMD respond inadequately to anti-VEGF therapy and suggest that the HIF inhibitor 32-134D will be an effective drug-alone or in combination with current anti-VEGF therapies-for the treatment of patients with this blinding disease.},
}
@article {pmid39498240,
year = {2024},
author = {Qaseem, Y and Hou, KK and Pettenkofer, MS},
title = {Outcomes After Switching to Faricimab for Refractive Macular Edema in Treatment-Experienced Eyes with Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3097-3102},
pmid = {39498240},
issn = {1177-5467},
abstract = {PURPOSE: To examine response to faricimab in neovascular age-related macular degeneration (nARMD) refractory to traditional anti-vascular endothelial growth factor (anti-VEGF) agents.<br><br>PATIENTS AND METHODS: Retrospective chart review was conducted on eyes with nARMD with persistent subretinal and/or intraretinal fluid despite previously receiving &#x2265;15 injections with &#x2265;2 different anti-VEGF agents. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters were collected at baseline, initial post-injection visit, and most recent visit with OCT following last faricimab.<br><br>RESULTS: Nineteen eyes were included. Average logMAR BCVA was 0.47 &#xb1; 0.60 at baseline, 0.42 &#xb1; 0.47 at initial follow-up (p=0.38), and 0.51 &#xb1; 0.63 at final visit (p = 0.50). Average central subfield thickness (CST) was 310 &#xb1; 92&#xa0;&#x3bc;m at baseline, 279 &#xb1; 88&#xa0;&#x3bc;m at initial follow-up (p = 0.001), and 274 &#xb1; 100&#xa0;&#x3bc;m at last visit (p < 0.001). 9 eyes (47%) achieved resolution of fluid at both initial and final follow-up visits.<br><br>CONCLUSION: Faricimab mildly decreased CST and reduced fluid in some nARMD eyes refractory to traditional anti-VEGF agents but had minimal effect on BCVA.},
}
@article {pmid39498038,
year = {2024},
author = {Zhao, L and Wu, P and Lu, J and He, Y and Shu, Q and Pan, F and Xie, H and Wang, X and Ju, H and Du, Y and Peng, H},
title = {Cigarette smoke extract induces ferroptosis in human retinal pigment epithelial cells.},
journal = {Heliyon},
volume = {10},
number = {20},
pages = {e38151},
pmid = {39498038},
issn = {2405-8440},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common blindness diseases. Retinal pigment epithelium (RPE) dysfunction due to smoking is an essential environmental factor in the pathogenesis of AMD. Ferroptosis is a novel type of iron-dependent programmed cell death (PCD). However, the relationship between cigarette smoke extract (CSE)-induced RPE damage and ferroptosis remains unclear.<br><br>METHODS: In our study, we extracted CSE using a modified device to explore the optimal concentration of CSE, and observed the expression of proteins and molecules after CSE exposure for ARPE-19&#xa0;cells by protein immunoblotting and assay kits for iron ions and mitochondrial membrane potential (MMP). At the same time, CSE was injected into the vitreous cavity of mice with a microsyringe for AMD modeling to observe the morphology of the retina-RPE-choroid complex and the differences expression of proteins. In addition, the protective effects of ferroptosis inhibitors on CSE-induced RPE cell damage were also investigated by in vivo and in vitro experiments.<br><br>RESULTS: In this study, we observed that CSE induced cellular damage in a human retinal pigment epithelial cell line (ARPE-19), resulting in ferrous ion (Fe[2+]) accumulation, an increas in reactive oxygen species (ROS) and lipid peroxidation (LP), a reduction in GSH levels, and the inhibition of Gpx4 expression. In addition, transmission electron microscopy (TEM) of in vivo and in vitro samples showed that after exposure to CSE, the mitochondria of RPE cells were wrinkled, the membrane density was increased, and the number of cristae decreased or cristae were not observed.<br><br>CONCLUSIONS: The results of this study indicate that the ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) protect RPE cells from CSE-induced ferroptosis, and this evidence paves the way for AMD studies.},
}
@article {pmid39497442,
year = {2025},
author = {Toma, C and Gatti, V and Servillo, A and Galotta, A and Leonardi, M and Ferrante, D and Torti, E and Leporati, F and Cillà, S},
title = {Early Choriocapillaris Dysfunction in Fellow Eyes of Patients with Unilateral Neovascular Age-Related Macular Degeneration.},
journal = {European journal of ophthalmology},
volume = {35},
number = {3},
pages = {1054-1060},
doi = {10.1177/11206721241293494},
pmid = {39497442},
issn = {1724-6016},
mesh = {Humans ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Male ; Female ; Fluorescein Angiography/methods ; *Wet Macular Degeneration/physiopathology/diagnosis ; Aged ; Visual Acuity/physiology ; Fundus Oculi ; *Capillaries/physiopathology ; Retrospective Studies ; Aged, 80 and over ; Regional Blood Flow/physiology ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {PurposeTo investigate early changes in AMD by evaluating and comparing choriocapillaris (CC) flow in fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) and in healthy controls using swept-source optical coherence tomography angiography (SS-OCTA).MethodsPatients with unilateral nAMD and no/early/intermediate AMD (no/e/iAMD) in their fellow eye and normal controls who underwent SS-OCT and OCTA where included. CC perfusion was assessed on MATLAB as percentage of flow deficits (FD%) in the central 4.5 × 4.5 mm macular region, after removing artifacts.Results81 eyes/patients (22 eyes with noAMD, 30 with eAMD, 29 with iAMD) with unilateral nAMD and 24 controls were analyzed. Median FD% was 8.97 (IQR 8.58-9.53) in AMD group, 8.92 (IQR 8.64-9.27) in noAMD group, 8.96 (IQR 8.46-9.38) in eAMD group, 9.05 (IQR 8.58-9.8) in iAMD group, and 8.22 (IQR 7.78-8.55) in controls. A statistically significant difference in FD% was observed between controls and AMD group (p < 0.001), as well as between each AMD subgroup and controls (noAMD vs controls p = 0.0037; eAMD vs control p = 0.0012; iAMD vs controls p = 0.0002).ConclusionThis study suggests that CC dysfunction may occur in fellow eyes of patients with unilateral nAMD before visible AMD signs, potentially preceding RPE changes. Further longitudinal studies are needed to confirm these findings and explore the correlation with AMD development/progression.},
}
@article {pmid39497194,
year = {2024},
author = {Tong, B and Long, C and Zhang, J and Zhang, X and Li, Z and Qi, H and Su, K and Zhang, D and Chen, Y and Ling, J and Liu, J and Hu, Y and Yu, P},
title = {Associations of human blood metabolome with optic neurodegenerative diseases: a bi-directionally systematic mendelian randomization study.},
journal = {Lipids in health and disease},
volume = {23},
number = {1},
pages = {359},
pmid = {39497194},
issn = {1476-511X},
support = {82160371//National Natural Science Foundation of China/ ; 82360204//National Natural Science Foundation of China/ ; 81760150//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Macular Degeneration/blood/genetics ; *Metabolome/genetics ; *Glaucoma/genetics/blood ; Neurodegenerative Diseases/genetics/blood ; Polymorphism, Single Nucleotide ; Male ; Female ; },
abstract = {BACKGROUND: Metabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited.<br><br>METHODS: Two-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies.<br><br>RESULTS: All the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases.<br><br>CONCLUSIONS: By integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD.},
}
@article {pmid39496987,
year = {2025},
author = {Lee, JH and Shin, JY and Ahn, J},
title = {First-year real-world experience of intravitreal brolucizumab injection for refractory neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {69},
number = {1},
pages = {43-48},
pmid = {39496987},
issn = {1613-2246},
mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Fluorescein Angiography/methods ; Follow-Up Studies ; Treatment Outcome ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Time Factors ; },
abstract = {PURPOSE: To investigate the first-year real-world anatomical and functional outcomes of intravitreal brolucizumab injection in eyes with refractory neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: nAMD patients who showed poor response to previous anti-vascular endothelial growth factor (VEGF) agents were switched to brolucizumab. Functional and anatomical outcomes were evaluated at initial treatment of nAMD, after treatment with other anti-VEGF agents and after switching and treating with brolucizumab for 1 year. Safety profile was also evaluated after brolucizumab injection. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and the presence of fluid in different compartments (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]) were assessed at each time point.<br><br>RESULTS: A total of 40 eyes of 40 patients were included in the study. BCVA remained unchanged throughout treatment (p&#x2009;>&#x2009;0.05). CFT did not change after treatment with other anti-VEGF agents (p&#x2009;=&#x2009;0.588) but decreased after switching to brolucizumab (p&#x2009;<&#x2009;0.001). SFCT decreased after treatment with other anti-VEGF agents (p&#x2009;=&#x2009;0.025) but not after switching to brolucizumab (p&#x2009;=&#x2009;0.236). Presence of SRF (p&#x2009;=&#x2009;0.001) and PED (p&#x2009;=&#x2009;0.001) decreased significantly after switching to brolucizumab, despite their persistence with prior treatments using other anti-VEGF agents. However, IRF persisted even after switching to brolucizumab (p&#x2009;=&#x2009;0.745). Intraocular inflammation (IOI)-related adverse events were reported in 3 eyes (7.14%).<br><br>CONCLUSION: Analysis of first-year real-world outcomes after switching to brolucizumab in nAMD patients refractory to other anti-VEGF agents showed improved anatomic outcomes, limited functional improvement and low incidence of IOI-related adverse events.},
}
@article {pmid39496825,
year = {2024},
author = {Tan, L and Ma, Z and Miao, Q and Liu, S and Li, Y and Ke, Y and Ren, X},
title = {Knowledge, attitudes, and practices of patients with age-related macular degeneration (AMD) towards Anti-VEGF treatment under one-stop intravitreal injection model.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {26563},
pmid = {39496825},
issn = {2045-2322},
support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; 2021D01F45//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; },
mesh = {Humans ; *Intravitreal Injections ; Male ; Aged ; Female ; *Health Knowledge, Attitudes, Practice ; *Macular Degeneration/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Cross-Sectional Studies ; Middle Aged ; Surveys and Questionnaires ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; },
abstract = {To evaluate the knowledge, attitudes, and practices (KAP) of patients with age-related macular degeneration (AMD) regarding anti-VEGF treatment within a one-stop intravitreal injection service model. A cross-sectional study was conducted from July 1, 2023, to January 31, 2024, at the One-stop Intravitreal Injection Center at Tianjin Medical University Eye Hospital. Data were collected using a specially designed KAP questionnaire. The study successfully enrolled 493 participants. Of these, 214 (43.4%) were aged between 70 and 79 years, and 226 (45.8%) had been diagnosed with AMD for 1-3 years. The median knowledge, attitude, and practice scores were 6.00 [3.00, 8.00] (possible range: 0-9), 42.00 [37.00, 48.00] (possible range: 11-55), and 23.00 [18.00, 27.00] (possible range: 6-30), respectively. Multivariate logistic regression for practice showed that knowledge score (OR = 1.329, P < 0.001), attitude score (OR = 1.150, P < 0.001), aged 60-69 years (OR = 0.398, P = 0.022) were independently associated with proactive practice. Mediating effect significance showed that knowledge directly affected attitude (β = 0.625), knowledge (β = 0.398) and attitude (β = 0.503) directly affected practice (P < 0.001). Meanwhile, knowledge also indirectly affected practice through attitude (β = 0.315, P < 0.001). Regarding the factors impacting their selection of anti-VEGF treatment, 63.5% of patients emphasized the crucial role of its effectiveness. Additionally, over 40% of patients considered both family circumstances and insurance coverage to be highly significant in their decision-making process. This study found that patients with AMD exhibit suboptimal knowledge yet hold positive attitudes and engage actively in practices concerning anti-VEGF treatment within a one-stop intravitreal injection service model. It is recommended that healthcare providers enhance educational interventions at intravitreal injection centers to boost patient knowledge, which is likely to further improve attitudes and proactive management practices among AMD patients.},
}
@article {pmid39496395,
year = {2024},
author = {Wang, MY and Gao, FJ and Ju, YQ and Guo, LY and Duan, C and Chang, Q and Zhang, T and Xu, GZ and Du, H and Zong, Y and Huang, X},
title = {Clinical and mutational signatures of CRB1-associated retinopathies: a multicentre study.},
journal = {Journal of medical genetics},
volume = {62},
number = {1},
pages = {6-14},
doi = {10.1136/jmg-2024-110289},
pmid = {39496395},
issn = {1468-6244},
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; *Eye Proteins/genetics ; *Genetic Association Studies ; Macular Degeneration/genetics/pathology ; *Membrane Proteins/genetics ; *Mutation/genetics ; *Nerve Tissue Proteins/genetics ; Phenotype ; Retina/pathology/metabolism ; *Retinal Diseases/genetics/pathology ; Retinitis Pigmentosa/genetics/pathology ; Retrospective Studies ; },
abstract = {BACKGROUND: To delineate the clinical and mutational signatures of patients with CRB1-associated retinopathies.<br><br>METHODS: This multicentre retrospective cohort study involved 40 patients with CRB1 mutations and 40 age-matched and gender-matched inherited retinal diseases (IRDs). The detailed phenotyping and genotyping characteristics and genotype&#x2012;phenotype correlations of the patients were analysed.<br><br>RESULTS: The mean age of CRB1 cohort was 27.33&#xb1;14.63 years. Results showed that yellowish geographic macular degeneration (66.67%), small white or yellow dots (65.6%), hyperopia (62.5%), abnormally laminated retina (61.61%), epiretinal membrane (60.6%) and nummular pigment deposits (50%) were the most common signatures in patients with CRB1 mutations. These clinical signatures were notably more prevalent among CRB1 patients than among individuals in other IRD groups (p<0.001). Early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) patients are more likely to present these signatures than retinitis pigmentosa (RP) and macular dystrophy (MD) patients. Furthermore, a significant reduction in central foveal thickness coupled with pronounced thickening of the peripheral retina was observed more distinctly in patients with EOSRD/LCA (p<0.001). The choroidal thickness was not significantly altered compared to the normal controls, but was markedly reduced in the other IRD groups (p<0.001). 55 pathogenic variants were identified, 20 of which were novel. Null mutations were associated with EOSRD/LCA patients, and missense mutations were more prevalent in MD and RP patients.<br><br>CONCLUSIONS: Key clinical and mutational signatures were demonstrated in this study, providing a comprehensive update on CRB1-associated retinopathies that will aid in diagnosis and lay the foundation for future therapeutic studies.},
}
@article {pmid39496246,
year = {2024},
author = {Vidal-Oliver, L and Spissinger, S and Herzig-de Almeida, E and Garzone, D and Finger, RP},
title = {Longitudinal Changes in Choroidal Thickness and Choroidal Vascularity Index in Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {654-661},
doi = {10.1159/000541481},
pmid = {39496246},
issn = {1423-0259},
mesh = {Humans ; *Choroid/blood supply/pathology/diagnostic imaging ; Male ; Female ; Aged ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Follow-Up Studies ; *Fluorescein Angiography/methods ; Disease Progression ; Visual Acuity ; Aged, 80 and over ; Macular Degeneration/diagnosis ; Fundus Oculi ; Wet Macular Degeneration/diagnosis ; Middle Aged ; },
abstract = {INTRODUCTION: The aim of the study was to investigate the rate of choroidal thinning and Choroidal Vascularity Index (CVI) changes over time in eyes with different stages of age-related macular degeneration (AMD) and control eyes.<br><br>METHODS: Retrospective longitudinal study of 105 eyes with different stages of AMD: non-advanced (n = 46), exudative (n = 28), central complete retinal pigment epithelium and outer retinal atrophy (cRORA) (n = 5) and healthy eyes (n = 26). We evaluated choroidal thickness (CT) and CVI at baseline and during 2-4 years of follow-up. After adjustment for age and sex, we estimated the rate of change per year of CT and CVI in each group. We also performed logistic regression to analyze the relationship between baseline CT and CVI with AMD progression.<br><br>RESULTS: The mean age of the included patients was 77.1 years with a mean follow-up of 3.36 years. Healthy eyes had higher baseline CT and CVI values compared to eyes with AMD. Exudative AMD showed a significant annual decrease in subfoveal CT (-5.1% per year vs. -3.5% in controls) and in the temporal and nasal sectors (-5.3% and -6.3%). CVI decreased during follow-up in all study groups, most in eyes with central cRORA (-1.09% per year).<br><br>CONCLUSION: CVI and CT values are reduced in eyes with AMD compared to healthy eyes. Eyes with exudative AMD have the highest annual rate of choroidal thinning, while CVI decreases most in eyes with central cRORA. CT and CVI may aid in a further stratification of AMD progression risk.},
}
@article {pmid39495383,
year = {2024},
author = {Thinggaard, BS and Hansen, K and Dinesen, F and Pedersen, MK and Morsø, L and Subhi, Y and Grauslund, J and Stokholm, L},
title = {Correction: The I-OPTA Questionnaire: A National Assessment of Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {12},
pages = {3047-3048},
doi = {10.1007/s40123-024-01063-1},
pmid = {39495383},
issn = {2193-8245},
}
@article {pmid39493839,
year = {2024},
author = {Rana, PJ and Deshmukh, H and Shah, U and Kumar, V and Kanungo, S and Singhal, D and Mahapatra, SK and Vakharia, I and Jaiswal, M and Gondane, A and Vaidya, P and Shahavi, V and Shandilya, H and Pawar, D and Sharma, A},
title = {Efficacy and Safety of Biosimilar Ranibizumab (OPTIMAB[®]) versus Innovator Ranibizumab in Patients with Neovascular (Wet) Age-Related Macular Degeneration: A Double-Blind, Randomized, Multicenter, Phase III Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {3071-3081},
pmid = {39493839},
issn = {1177-5467},
abstract = {OBJECTIVE: This study aimed to compare efficacy, safety, and immunogenicity of the biosimilar ranibizumab in comparison with the Innovator Ranibizumab in treatment-naive patients with neovascular (wet) age-related macular degeneration (nAMD or wAMD).<br><br>MATERIALS AND METHODS: This comparative, double blind, multicentre, Phase III clinical study randomized eligible patients in a 3:1 ratio to receive either OPTIMAB[&#xae;] (Alkem Laboratories Ltd./ Enzene Biosciences Ltd.) or Innovator Ranibizumab. Intravitreal injections of Innovator Ranibizumab (0.5 mg in 0.05 mL) and OPTIMAB[&#xae;] (0.5 mg in 0.05 mL) were administered every four weeks for 12&#xa0;weeks (three doses). Primary efficacy endpoints included loss of <15 letters from baseline, gain of &#x2265;15 letters from baseline in visual acuity, mean change in best corrected visual acuity (BCVA) from baseline, and change in central subfoveal thickness (CSFT) from baseline at week 12. Safety was assessed through monitoring of adverse events (AEs) and serious adverse events (SAEs) throughout the study.<br><br>RESULTS: Overall, of the 152 patients randomized, 141 (92.8%) patients (mean age, 66.6 &#xb1; 9.37 years) completed the study. Percentage of patients who lost < 15 letters in BCVA at week 12 from baseline was comparable in both the groups (100.0%, each). On secondary end point analysis, the two groups had comparable mean changes in BCVA (OPTIMAB[&#xae;], 11.8 &#xb1; 9.18; innovator ranibizumab, 12.9 &#xb1; 10.29; P =&#xa0;0.5509); proportion of patients who gained &#x2265; 15 letters in visual acuity (OPTIMAB[&#xae;], 32.18%; innovator ranibizumab, 25.74%; P = 0.4785) and mean change in CSFT (OPTIMAB[&#xae;], -76.6 &#xb1; 89.03; Innovator ranibizumab, -73.1 &#xb1; 92.23&#xa0;&#x3bc;m; P = 0.8422) at week 12 as compared to baseline. OPTIMAB[&#xae;] and innovator ranibizumab demonstrated comparable safety over the 12-week treatment period and no patient expressed anti-ranibizumab antibody in either group patient.<br><br>CONCLUSION: Biosimilar ranibizumab (OPTIMAB[&#xae;]) was non-inferior to innovator ranibizumab in terms of efficacy, safety, and immunogenicity in the patients of nAMD.},
}
@article {pmid39493522,
year = {2024},
author = {Sharmin, S and Rashid, MR and Khatun, T and Hasan, MZ and Uddin, MS and Marzia, },
title = {A dataset of color fundus images for the detection and classification of eye diseases.},
journal = {Data in brief},
volume = {57},
number = {},
pages = {110979},
pmid = {39493522},
issn = {2352-3409},
abstract = {The retina is a critical component of the eye responsible for capturing visual information, making the importance of retinal health for clear vision. Various eye diseases, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, can severely impair vision and even lead to blindness if not detected and treated early. Therefore, automated systems using machine learning and computer vision techniques have shown promise in the early detection and management of these diseases, reducing the risk of vision loss. In this context, to facilitate the development and evaluation of machine learning models for eye disease detection, we introduced a comprehensive dataset which was collected during a span of eight months from Anawara Hamida Eye Hospital &amp; B.N.S.B. Zahurul Haque Eye Hospital using Color Fundus Photography machine. The dataset has two categories of data: color fundus photographs and anterior segment images. The color fundus photographs categorized into nine classes: Diabetic Retinopathy, Glaucoma, Macular Scar, Optic Disc Edema, Central Serous Chorioretinopathy (CSCR), Retinal Detachment, Retinitis Pigmentosa, Myopia, Healthy and anterior segment images has one class: Pterygium. This dataset comprises 5335 primary images. By providing a rich and diverse collection of color fundus photographs, this dataset serves as a valuable resource for researchers and clinicians in the field of ophthalmology for the automatic detection of nine different classes of eye diseases.},
}
@article {pmid39493394,
year = {2024},
author = {Kim, BK and Kim, KU and Kim, J and Jang, H and Min, H},
title = {The protective effect of 20(S)-ginsenoside Rg3 on the human retinal pigment epithelial cells against hydrogen peroxide-induced oxidative stress.},
journal = {Food science and biotechnology},
volume = {33},
number = {15},
pages = {3607-3616},
pmid = {39493394},
issn = {2092-6456},
abstract = {Ginsenosides, constituting 2-3% of Panax ginseng Meyer, are noteworthy for their anticancer and antioxidant effects. Despite demonstrating promise in various diseases, their specific impact on age-related macular degeneration (AMD) remains unclear. This research investigates whether ginsenosides can inhibit the progression of dry AMD and explores the mechanisms by which they influence apoptosis, providing insight into their regulatory role in programmed cell death. Human retinal pigment epithelial (ARPE-19) cells were pre-treated with ginsenosides, followed by induction of oxidative stress using hydrogen peroxide. Pre-treatment with 20(S)-ginsenoside Rg3 significantly increased cell viability and reduced apoptotic markers, including Annexin V, Bax, Bim S, cleaved caspase 3, cleaved caspase 9, and cleaved PARP. Furthermore, 20(S)-ginsenoside Rg3 effectively diminished the activation of the ERK and NF-κB signaling pathways. 20(S)-ginsenoside Rg3 could be a good prevention for AMD by modulating apoptosis, offering valuable therapeutic insights for AMD.},
}
@article {pmid39491736,
year = {2024},
author = {Shang, P and Ambrosino, H and Hoang, J and Geng, Z and Zhu, X and Shen, S and Eminhizer, M and Hong, E and Zhang, M and Qu, J and Du, J and Montezuma, SR and Dutton, JR and Ferrington, DA},
title = {The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium.},
journal = {Free radical biology &amp; medicine},
volume = {225},
number = {},
pages = {833-845},
pmid = {39491736},
issn = {1873-4596},
support = {R01 EY026030/EY/NEI NIH HHS/United States ; R01 EY031324/EY/NEI NIH HHS/United States ; R01 EY032462/EY/NEI NIH HHS/United States ; R01 EY031720/EY/NEI NIH HHS/United States ; R01 EY028554/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Complement Factor H/genetics/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/genetics/metabolism/pathology ; *Oxidative Stress ; *Polymorphism, Single Nucleotide ; Induced Pluripotent Stem Cells/metabolism ; Mitochondria/metabolism/pathology/genetics ; Genotype ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of central vision loss in the elderly, involves death of the retinal pigment epithelium (RPE) and light-sensing photoreceptors. This multifactorial disease includes contributions from both genetic and environmental risk factors. The current study examined the effect of the Y402H polymorphism of Complement Factor H (CFH, rs1061170) and cigarette smoke, predominant genetic and environmental risk factors associated with AMD. We used targeted and discovery-based approaches to identify genotype-dependent responses to chronic oxidative stress induced by cigarette smoke extract (CSE) in RPE differentiated from induced pluripotent stem cells (iPSC) derived from human donors harboring either the low risk (LR) or high risk (HR) CFH genotype. Chronic CSE altered the metabolic profile in both LR and HR iPSC-RPE and caused a dose-dependent reduction in mitochondrial function despite an increase in mitochondrial content. Notably, cells with the HR CFH SNP showed a greater reduction in maximal respiration and ATP production. Significant genotype-dependent changes in the proteome were observed for HR RPE at baseline (cytoskeleton, MAPK signaling) and after CSE exposure, where a less robust upregulation of the antioxidants and significant downregulation in proteins involved in nucleic acid metabolism and membrane trafficking were noted compared to LR cells. In LR cells, uniquely upregulated proteins were involved in lipid metabolism and chemical detoxification. These genotype-dependent differences at baseline and in response to chronic CSE exposure suggest a broader role for CFH in modulating the response to oxidative stress in RPE and provides insight into the interaction between environmental and genetic factors in AMD pathogenesis.},
}
@article {pmid39490725,
year = {2024},
author = {Chen, J and Liu, Z and Zhu, Y and Li, Z and Wen, Y and Chen, D and Liang, J and Xiao, Y and Leng, Y and Zhuo, Y},
title = {Integrative multiomic analysis unveils the molecular nexus of mitochondrial dysfunction in the pathogenesis of age-related macular degeneration.},
journal = {Experimental eye research},
volume = {249},
number = {},
pages = {110141},
doi = {10.1016/j.exer.2024.110141},
pmid = {39490725},
issn = {1096-0007},
mesh = {*Macular Degeneration/genetics/metabolism ; Humans ; *Mitochondria/metabolism/genetics ; NF-kappa B p50 Subunit/genetics/metabolism ; Quantitative Trait Loci ; DNA Methylation ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Male ; HSP70 Heat-Shock Proteins/genetics/metabolism ; },
abstract = {Mitochondrial dysfunction is linked to age-related macular degeneration (AMD), but its mechanisms and related molecular networks remain unclear. We explored the association between mitochondrial-related genes and AMD by integrating multiomic data. We acquired summary-level data on mitochondrial-related protein abundance, gene expression, and gene methylation from quantitative trait locus studies. Genetic associations with AMD were sourced from the International Age-related Macular Degeneration Genomics Consortium (discovery), FinnGen (replication), and UK Biobank (replication) studies. We used summary-data-based Mendelian randomization to assess the correlations between mitochondrial-related gene molecular characteristics and AMD. Furthermore, colocalization analysis was performed to ascertain if the detected signal pairings had a common causative genetic variation. Mitochondrial-related gene NFKB1 demonstrated a protective role in AMD (tier 1 evidence), whereas HSPA1A and HSPA1B genes were also associated with decreased AMD risk (tier 2 evidence). The methylation of cg09390974 and cg15409712 in NFKB1 was associated with increased NFKB1 expression, consistent with the protective effect on AMD risk, whereas inverse associations were observed between gene methylation and gene expression for HSPA1B (cg04835051 and cg16372051), supporting the risk roles of methylation in AMD. At circulating protein level, genetically predicted higher levels of HSPA1A (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.19-0.41, P < 0.001), HSPA1B (OR 0.13, 95% CI 0.06-0.27, P < 0.001), and NFKB1 (OR 0.43, 95% CI 0.27-0.68, P < 0.001) were inversely associated with AMD risk. These associations were corroborated in the colocalization analysis. We identified AMD-linked mitochondrial-related genes, potentially improving the understanding of its pathophysiological mechanisms and aiding the identification of novel pharmaceutical targets.},
}
@article {pmid39490420,
year = {2024},
author = {Zhang, XL and Yue, YX and Yang, Y and Ying, AK and Ma, R and Chen, J and Chen, FY and Hou, XY and Pan, YC and Ren, DZ and Yang, T and Li, ZQ and Guo, DS},
title = {A single molecule carrier for ocular posterior segment diseases.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {376},
number = {},
pages = {1316-1328},
doi = {10.1016/j.jconrel.2024.10.052},
pmid = {39490420},
issn = {1873-4995},
mesh = {Animals ; *Drug Carriers/chemistry ; *Ophthalmic Solutions/administration &amp; dosage ; *Posterior Eye Segment/drug effects ; *Sunitinib/administration &amp; dosage/chemistry ; Calixarenes/chemistry ; Wet Macular Degeneration/drug therapy ; Humans ; Drug Delivery Systems ; Angiogenesis Inhibitors/administration &amp; dosage/chemistry/therapeutic use ; Rabbits ; },
abstract = {Eye drops are envisaged as the most promising non-invasive formulation for the treatment of the ocular posterior segment diseases, while it is hindered by a series of complex ocular barriers, both static and dynamic in nature. In this context, we propose a single molecule nanomedicine based on host-guest chemistry to achieve highly efficient drug delivery targeted to ocular posterior segment. Sulfonated azocalix[4]arene (SAC4A) serves as the single molecule carrier, owing the multiple features of small size (24.0 Å in length, 21.2 Å in width, 14.8 Å in height with a Van der Waals volume of 930 Å[3]), negative charge, hydrophilicity, loading universality and hypoxia-triggered release. As a proof-of-concept, an eye drop formed by the complexation of SAC4A with sunitinib (SUN) is prepared to treat wet age-related macular degeneration (wAMD). SAC4A successfully transports SUN to the ocular posterior segment (the amount of SUN reaching the retinal-choroid tissue in the SUN@SAC4A group was 2.47 times larger than that in the SUN group at 30 min), significantly enhancing its anti-choroidal neoangiogenesis effect of SUN to wAMD, which played a key role in the treatment. We believe that the single molecule nanomedicine paradigm is highly amenable for treating various ocular posterior segment diseases in the future.},
}
@article {pmid39489378,
year = {2025},
author = {Morino, K and Miyake, M and Nagasaki, M and Kawaguchi, T and Numa, S and Mori, Y and Yasukura, S and Akada, M and Nakao, SY and Nakata, A and Hashimoto, H and Otokozawa, R and Kamoi, K and Takahashi, H and Tabara, Y and Matsuda, F and Ohno-Matsui, K and Tsujikawa, A and , },
title = {Genome-wide Meta-analysis for Myopic Macular Neovascularization Identified a Novel Susceptibility Locus and Revealed a Shared Genetic Susceptibility with Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {4},
pages = {367-377},
doi = {10.1016/j.oret.2024.09.016},
pmid = {39489378},
issn = {2468-6530},
mesh = {Humans ; *Genome-Wide Association Study/methods ; *Genetic Predisposition to Disease ; *Polymorphism, Single Nucleotide ; *Myopia, Degenerative/complications/genetics/diagnosis ; Male ; Female ; *Macular Degeneration/genetics ; *Choroidal Neovascularization/genetics/etiology ; },
abstract = {PURPOSE: To identify the susceptibility loci for myopic macular neovascularization (mMNV) in patients with high myopia.<br><br>DESIGN: A genome-wide association study (GWAS) meta-analysis (meta-GWAS).<br><br>PARTICIPANTS: We included 2783 highly myopic individuals, including 608 patients with mMNV and 2175 control participants without mMNV.<br><br>METHODS: We performed a meta-analysis of 3 independent GWASs conducted according to the genotyping platform (Illumina Asian Screening Array [ASA] data set, Illumina Human610 BeadChip [610K] data set, and whole genome sequencing [WGS] data set), adjusted for age, sex, axial length, and the first to third principal components. We used DeltaSVM to evaluate the binding affinity of transcription factors (TFs) to DNA sequences around the susceptibility of single nucleotide polymorphisms (SNPs). In addition, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci.<br><br>MAIN OUTCOME MEASURES: The association between SNPs and mMNV in patients with high myopia.<br><br>RESULTS: The meta-GWAS identified rs56257842 at TEX29- LINC02337 as a novel susceptibility SNP for mMNV (odds ratio [OR]meta&#xa0;= 0.62, Pmeta&#xa0;= 4.63&#xa0;&#xd7; 10[-8], I[2]&#xa0;= 0.00), which was consistently associated with mMNV in all data sets (ORASA&#xa0;= 0.59, PASA&#xa0;= 1.71&#xa0;&#xd7; 10[-4]; OR610K&#xa0;= 0.63, P610K&#xa0;= 5.53&#xa0;&#xd7; 10[-4]; ORWGS&#xa0;= 0.66, PWGS&#xa0;= 4.38&#xa0;&#xd7; 10[-2]). Transcription factor-wide analysis showed that the TFs ZNF740 and EGR1 lost their binding affinity to this locus when rs56257842 had the C allele (alternative allele), and the WNT signaling-related TF ZBTB33 gained binding affinity when rs56257842 had the C allele. When we examined the associations of AMD susceptibility loci, rs12720922 at CETP showed a statistically significant association with mMNV (ORmeta&#xa0;= 0.52, Pmeta&#xa0;= 1.55&#xa0;&#xd7; 10[-5]), whereas rs61871745 near ARMS2 showed a marginal association (ORmeta&#xa0;= 1.25, Pmeta&#xa0;=&#xa0;7.79&#xa0;&#xd7; 10[-3]).<br><br>CONCLUSIONS: Our study identified a novel locus associated with mMNV in high myopia. Subsequent analyses offered important insights into the molecular biology of mMNV, providing the potential therapeutic targets for mMNV. Furthermore, our findings imply shared genetic susceptibility between mMNV and AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39485018,
year = {2024},
author = {Chen, J and Chen, X and Zhu, Y and Li, Z and Chen, X and Cao, X and Li, Y and Wen, Y and Liu, L and Xiao, Y and Zhan, J and Huang, H and Zheng, Y and Li, Y and Wei, Y and Zhuo, Y},
title = {Quantifying the impact of disease severity changes on the burden of blindness: A global decomposition analysis.},
journal = {Journal of global health},
volume = {14},
number = {},
pages = {04248},
pmid = {39485018},
issn = {2047-2986},
mesh = {Humans ; *Blindness/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Severity of Illness Index ; *Global Burden of Disease ; *Disability-Adjusted Life Years ; *Global Health/statistics &amp; numerical data ; Cost of Illness ; Prevalence ; Quality-Adjusted Life Years ; Aged ; Middle Aged ; },
abstract = {BACKGROUND: Despite the significant impact of blindness on the affected individuals' quality of life, its burden has not been assessed according to temporal cause-specific changes in severity, impeding our ability to evaluate the impact of blindness on population health accurately. Therefore, we aimed to comprehensively quantify the changes in cause-specific blindness burden according to changes in disease severity for 18 causes of blindness.<br><br>METHODS: For this cross-sectional population-based study, we derived data on prevalence, disability-adjusted life-years (DALYs), and population size between 1990 and 2019 from the Global Burden of Disease 2019 study. Using the decomposition method, we attributed changes in total DALYs to population growth, population ageing, and changes in prevalence rate and disease severity between 1990 and each subsequent year globally, regionally, nationally, and by sex, cause, and sociodemographic index (SDI). The absolute and relative contributions to the variation in blindness-related DALYs between 1990 and each year from 1991 to 2019 then served as a measure of changes in disease severity.<br><br>RESULTS: Changes in disease severity from 1990 to 2019 were associated with 15&#x2009;165.11 DALYs in men and 20&#x2009;639.32 DALYs in women. We observed disease severity increases in most countries/territories, with attributable DALY proportions ranging from -0.07% to 1.30% in men and from -0.06% to 1.73% in women. Notably, both attributable proportions and DALYs were greater in women than men. The largest increases in attributable DALYs were observed for cataracts, refraction disorders, and glaucoma globally; age-related macular degeneration in high-SDI countries; and trachoma and retinopathy of prematurity in lower-SDI countries.<br><br>CONCLUSIONS: Growth in the burden of cause-specific blindness due to increased disease severity reflects the lag of healthy vision life behind increasing life expectancy, necessitating the implementation of preventive and long-term therapeutic measures focussed on improving visual outcomes.},
}
@article {pmid39483584,
year = {2024},
author = {Bilal, A and Bilal, M and Hathaf, A and Usman, D and Haboubi, N},
title = {The Weight on Sight: Exploring the Links Between Obesity and Ocular Diseases.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e72742},
pmid = {39483584},
issn = {2168-8184},
abstract = {Obesity is a significant public health concern with escalating levels worldwide creating a variety of socioeconomic challenges and imposing a serious risk factor for a range of complications which include diabetes, hypertension, cardiovascular disease, and stroke, all of which are primary causes of early death. Furthermore, there is growing evidence connecting obesity to the development of several ocular disorders. Excessive weight is a common denominator in the aetiology of many ocular pathologies such as diabetic retinopathy, idiopathic intracranial hypertension, cataract, high intraocular pressures, age-related macular degeneration, and retinal vascular diseases through the association with diabetes, hypertension, and dyslipidemia. This review highlights the risks weight gain and a sedentary lifestyle imposes on patients' ocular health and aims to inform the public and raise awareness about the consequences obesity has on sight. This review explores articles available on Ovid-MEDLINE (Medical Literature Analysis and Retrieval System Online) and PubMed regarding the impact of obesity on ocular health and the pathogenesis of obesity-linked ocular diseases.},
}
@article {pmid39482729,
year = {2024},
author = {Liu, H and Huang, SS and Lingam, G and Kai, D and Su, X and Liu, Z},
title = {Advances in retinal pigment epithelial cell transplantation for retinal degenerative diseases.},
journal = {Stem cell research &amp; therapy},
volume = {15},
number = {1},
pages = {390},
pmid = {39482729},
issn = {1757-6512},
support = {MOH-001357-00//National Medical Research Council/ ; M22N2K0007//National Additive Manufacturing Innovation Cluster/ ; NRF-CRP21-2018-00103//National Research Foundation Singapore/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/transplantation/cytology/metabolism ; *Retinal Degeneration/therapy ; Animals ; Tissue Scaffolds/chemistry ; },
abstract = {Retinal degenerative diseases are a leading cause of vision loss and blindness globally, impacting millions. These diseases result from progressive damage to retinal pigment epithelial (RPE) cells for which no curative or palliative treatments exist. Cell therapy, particularly RPE transplantation, has emerged as a promising strategy for vision restoration. This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation. We discuss scaffold-free and scaffold-based approaches, including RPE cell suspensions and pre-organized RPE monolayers on biomaterial scaffolds. Key considerations, such as the form and preparation of RPE implants, delivery devices, strategies, and biodegradability of scaffolds, are examined. The article also explores the challenges and opportunities in RPE scaffold development, emphasising the crucial need for functional integration, immunomodulation, and long-term biocompatibility to ensure therapeutic efficacy. We also highlight ongoing efforts to optimise RPE transplantation methods and their potential to address retinal degenerative diseases.},
}
@article {pmid39482668,
year = {2024},
author = {Shen, G and Chen, Y and Chen, J and Wang, L and Cheng, H and Hu, B and Gong, J},
title = {The causal effects of lifestyle, circulating, pigment, and metabolic factors on early age-related macular degeneration: a comprehensive Mendelian randomization study.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {988},
pmid = {39482668},
issn = {1479-5876},
mesh = {Humans ; *Macular Degeneration/genetics/blood ; *Mendelian Randomization Analysis ; *Life Style ; *Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide/genetics ; Causality ; Pigmentation/genetics ; },
abstract = {PURPOSE: Early detection of lifestyle factors, skin and hair color, circulating parameters, and metabolic comorbidities is crucial for personalized prevention and treatment of early age-related macular degeneration (AMD). This study aimed to assess the relationships between genetically predicted comprehensive risk factors and early AMD.<br><br>METHODS AND RESULTS: Publicly available genome-wide association study (GWAS) data were utilized to identify genetic variants significantly associated with each trait. We applied a Bonferroni-corrected significance level of P&#x2009;<&#x2009;0.0017. P values between 0.0017 and 0.05 were considered suggestive associations. Univariable Mendelian randomization (MR) analyses revealed that elevated serum HDL-C, lower serum TG, and decreased three circulating fatty acids levels were robust indicators of an increased risk of early AMD (all P&#x2009;<&#x2009;0.0017), with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.218 (1.140-1.303), 0.784 (0.734-0.837), 0.772 (0.698-0.855), 0.776 (0.706-0.852), and 0.877 (0.798-0.963), respectively. Additionally, the "never eat wheat products", "age started wearing glasses", and "skin color" were significantly associated with the risk of early AMD (both P&#x2009;<&#x2009;0.0017), with ORs (95% CIs) of 23.853 (2.731-208.323), 1.605 (1.269-2.030) and 1.190 (1.076-1.317), respectively. Multivariable MR analysis confirmed that elevated serum HDL-C (OR&#x2009;=&#x2009;1.187, 1.064-1.324) increased the risk of early AMD, while higher serum TG (OR&#x2009;=&#x2009;0.838, 0.738-0.950) was associated with a significantly lower risk. Furthermore, validation results indicated that serum HDL-C 1.201 (1.101-1.310) and TG 0.795 (0.732-0.864) were significantly associated with the risk of early AMD. There were suggestive associations of smoothies, chronotype, and hair color (0.0017&#x2009;<&#x2009;P&#x2009;<&#x2009;0.05), but sun/UV protection, smoking, BMI, diabetes, high blood pressure, cardiovascular diseases, fresh fruit intake, fish oil/cod liver oil supplement, sleeplessness, serum C-reactive protein level, and iron level were not associated with the risk of early AMD.<br><br>CONCLUSIONS: Our comprehensive MR analysis demonstrated that elevated circulating HDL-C levels increase the risk of early AMD, while TG and fatty acid levels are associated with a decreased risk. These findings provide robust evidence for improved diagnosis and personalized prevention and treatment of early AMD.},
}
@article {pmid39482583,
year = {2024},
author = {Hu, J and Zhang, J and Liu, Y and Qin, J and Bai, H and Qin, X},
title = {Causal linkage of Graves' disease with aging: Mendelian randomization analysis of telomere length and age-related phenotypes.},
journal = {BMC geriatrics},
volume = {24},
number = {1},
pages = {901},
pmid = {39482583},
issn = {1471-2318},
support = {2018YFE0207300//National Key Research and Development Program of China/ ; 345 Talent Project//Shengjing Hospital of China Medical University/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Graves Disease/genetics/epidemiology ; *Aging/genetics ; *Genome-Wide Association Study/methods ; *Phenotype ; Telomere ; Telomere Homeostasis/physiology ; Female ; Male ; Aged ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Aging is an irreversible progressive decline in physical function. Graves' disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated.<br><br>METHODS: We used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R[2] were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I[2], MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes.<br><br>RESULTS: F-statistics of the five IVs were greater than 10, and the R[2] values ranged from 0.033 to 0.156 (R[2]&#x2009;>&#x2009;0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p&#x2009;=&#x2009;0.189), age-related macular degeneration (p&#x2009;=&#x2009;0.346), and Alzheimer's disease (p&#x2009;=&#x2009;0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR&#x2009;=&#x2009;0.982; 95%CI:0.969-0.994; p&#x2009;=&#x2009;0.004), senile cataract (OR&#x2009;=&#x2009;1.031; 95%CI:1.002-1.060; p&#x2009;=&#x2009;0.033), age-related hearing impairment (OR&#x2009;=&#x2009;1.009; 95%CI:1.004-1.014; p&#x2009;=&#x2009;0.001), chronic obstructive pulmonary disease (COPD) (OR&#x2009;=&#x2009;1.055; 95%CI:1.008-1.103; p&#x2009;=&#x2009;0.020), and sarcopenia (OR&#x2009;=&#x2009;1.027; 95%CI:1.009-1.046; p&#x2009;=&#x2009;0.004).<br><br>CONCLUSIONS: GD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer's disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.},
}
@article {pmid39480573,
year = {2025},
author = {Lu, J and He, Y and Du, Y and Zhao, L and Wu, P and Shu, Q and Peng, H and Wang, X},
title = {Atorvastatin Alleviates Age-Related Macular Degeneration via AIM2-Regulated Pyroptosis.},
journal = {Inflammation},
volume = {48},
number = {4},
pages = {2122-2136},
pmid = {39480573},
issn = {1573-2576},
support = {81670881//National Natural Science Foundation of China/ ; CSTB2024NSCQ-MSX0705//Natural Science Foundation of Chongqing&#xff0c;China/ ; },
mesh = {*Pyroptosis/drug effects/physiology ; *Macular Degeneration/drug therapy/metabolism/pathology/chemically induced ; Animals ; *Atorvastatin/pharmacology/therapeutic use ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Humans ; Caspase 1/metabolism ; Mice ; Phosphate-Binding Proteins/metabolism ; },
abstract = {The underlying causes of age-related macular degeneration (AMD) remain elusive and treatment options of it are limited, while atorvastatin (AT) is expected to improve AMD. Our study sought to uncover the specific mechanisms that initiate pyroptosis in AMD and elucidate whether AT ameliorates Aβ1-40-induced retinal damage by inhibiting pyroptosis. An animal model of AMD was triggered by Aβ1-40, and the therapeutic efficacy of AT was evaluated by hematoxylin and eosin staining (H&amp;E), Optical Coherence Tomography (OCT), Electroretinogram (ERG) and other methods. Utilizing network pharmacology in conjunction with transcriptomics, we identified potential therapeutic pathways. we employed Western blotting (WB) and quantitative real-time PCR (qPCR) methodologies to evaluate the levels of pyroptosis. In vitro system of retinal pigment epithelium (RPE) cells injury was caused by Aβ1-40 and subsequently treated with AT or JC2-11. The extent of pyroptosis was quantified using enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and WB. Cell morphological changes were examined using light microscopy and scanning electron microscopy. Network pharmacology and transcriptomics identified AIM2/Caspase-1/GSDMD as the key pathway. AT improved the retinal morphological and functional damage caused by Aβ1-40, and decreased the production of AIM2, Asc, Caspase-1, GSDMD-N, Cleaved Caspase-1 and cytokines to exert an anti-inflammatory effect. In addition, AT improved the ruptured membrane of RPE cells caused by Aβ1-40. The use of JC2-11 further demonstrated that AT inhibits pyroptosis of RPE via AIM2/Caspase-1/GSDMD pathway activated by Aβ1-40. These discoveries illuminate the retinal conservation role of AT by effectively hindering the progression of pyroptosis.},
}
@article {pmid39480559,
year = {2025},
author = {Ohji, M},
title = {Submacular hemorrhage: My personal journey to the goal.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {4},
pages = {901-908},
pmid = {39480559},
issn = {1435-702X},
mesh = {Humans ; *Retinal Hemorrhage/diagnosis/etiology/therapy/surgery ; *Vitrectomy/methods ; *Visual Acuity ; Intravitreal Injections ; Tomography, Optical Coherence ; Tissue Plasminogen Activator/administration &amp; dosage ; },
abstract = {Acute submacular hemorrhage (SMH) can be caused by various diseases including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and retinal arterial microaneurysm (RAM). The natural course of submacular hemorrhage is generally poor. Animal studies have suggested that the removal of subretinal hemorrhage may effectively reduce retinal damage caused by hemorrhage in humans and removal of submacular hemorrhage have been performed with limited visual outcomes. Pneumatic displacement involving intravitreal expansile gas with or without adjunctive intravitreal injection of tissue plasminogen activator (tPA) has demonstrated effective displacement of SMH and improvement in visual acuity in the majority of cases. Although tPA may not be indispensable, its use may facilitate displacement. Combining pneumatic displacement with vitrectomy and subretinal injection of tPA may achieve superior displacement of SMH compared to pneumatic displacement of SMH, implying that pneumatic displacement of SMH with vitrectomy and subretinal injection may offer enhanced effectiveness in SMH displacement, while no obvious different was found in visual outcomes between the two treatments. Complications associated with these procedures encompass breakthrough hemorrhage, retinal detachment and macular hole formation. Breakthrough hemorrhage is more commonly observed following pneumatic displacement whereas retinal detachment appears to be more prevalent following vitrectomy. Macular hole formation subsequent to vitrectomy represents a significant complication, particularly in eyes with SMH attributed to ruptured retinal arterial microaneurysm. Both pneumatic displacement and vitrectomy present advantages and disadvantages, and the superiority between the two remains undetermined. Sequential strategy for the treatment of submacular hemorrhage is another option. As the initial step, pneumatic displacement of SMH should be attempted, and if displacement is insufficient, pneumatic displacement following vitrectomy with subretinal injection of tPA may be pursued. Further investigations are warranted to ascertain optimal management strategies for SMH leading to improved outcomes. KEY MESSAGES: What is known • Pneumatic displacement with/without intravitreal tPA injection, and vitrectomy with subretinal tPA injection and gas are the two major treatments for submacular hemorrhage. What is new • No obvious different was found in visual outcomes between vitrectomy, subretinal tPA injection and gas, and intravitreal tPA injection and gas while vitrectomy with subretinal tPA injection and gas may achieve better displacement of submacular hemorrhage. • Macular hole formation is a specific complication for submacular hemorrhage due to ruptured retinal arterial macroaneurysm.},
}
@article {pmid39487449,
year = {2024},
author = {Thomsen, AK and Steffensen, MA and Villarruel Hinnerskov, JM and Nielsen, AT and Vorum, H and Honoré, B and Nissen, MH and Sørensen, TL},
title = {Complement proteins and complement regulatory proteins are associated with age-related macular degeneration stage and treatment response.},
journal = {Journal of neuroinflammation},
volume = {21},
number = {1},
pages = {284},
pmid = {39487449},
issn = {1742-2094},
mesh = {Humans ; Male ; Female ; Aged ; *Complement System Proteins/metabolism ; *Macular Degeneration/drug therapy ; Aged, 80 and over ; Middle Aged ; Prospective Studies ; Treatment Outcome ; },
abstract = {BACKGROUND: Dysregulation of the complement system is involved in development of age-related macular degeneration (AMD). The complement cascade is regulated by membrane bound complement regulatory proteins (Cregs) on mononuclear leukocytes among others. This study aims to investigate systemic complement proteins and Cregs in AMD stages and their association with treatment response in neovascular AMD (nAMD).<br><br>METHODS: In this clinical prospective study, treatment-na&#xef;ve patients with nAMD, intermediate AMD (iAMD) and healthy controls were recruited and systemic complement proteins C3, C3a and C5a were investigated with electrochemiluminescence immunoassays, and Creg expression (CD35, CD46 and CD59) on T cells (CD4&#x2009;+&#x2009;and CD8+) and monocytes (classical, intermediate and non-classical) investigated with flow cytometry. Treatment response in nAMD patients was evaluated after loading dose and after one year, and categorized as good, partial or poor. Complement proteins and Creg expression levels were compared between healthy controls, iAMD and nAMD, as well as between good, partial and poor nAMD treatment response groups. Polymorphisms in the CFH and ARMS2 genes were analyzed and compared to complement proteins and Creg expression levels in nAMD patients.<br><br>RESULTS: One hundred patients with nAMD, 34 patients with iAMD and 61 healthy controls were included. 94 nAMD patients completed the 1-year follow-up. Distribution of treatment response in nAMD was 61 (65%) good, 26 (28%) partial, and 7 (7%) poor responders. The distribution of 1-year treatment response was 50 (53%) good, 33 (36%) partial, and 11 (11%) poor responders. The concentrations of systemic C3, C3a, and the C3a/C3-ratio were significantly increased in patients with nAMD compared to healthy controls (P&#x2009;<&#x2009;0.001, P&#x2009;=&#x2009;0.002, and P&#x2009;=&#x2009;0.035, respectively). Systemic C3 was also increased in iAMD compared to healthy controls (P&#x2009;=&#x2009;0.031). The proportion of CD46&#x2009;+&#x2009;CD4&#x2009;+&#x2009;T cells and CD59&#x2009;+&#x2009;intermediate monocytes were significantly decreased in patients with nAMD compared to healthy controls (P&#x2009;=&#x2009;0.018 and P&#x2009;=&#x2009;0.042, respectively). The post-loading dose partial treatment response group had significantly lower concentrations of C3a and C5a compared to the good response group (P&#x2009;=&#x2009;0.005 and P&#x2009;=&#x2009;0.042, respectively). The proportion of CD35&#x2009;+&#x2009;monocytes was significantly lower in the 1-year partial response group compared to the 1-year good response group (P&#x2009;=&#x2009;0.039). High-risk CFH genotypes in nAMD patients was associated with increased C3a, C3a/C3-ratio, and expression levels of CD35&#x2009;+&#x2009;CD8&#x2009;+&#x2009;T cells and CD46&#x2009;+&#x2009;classical monocytes, while expression level of CD46&#x2009;+&#x2009;non-classical monocytes was decreased.<br><br>CONCLUSION: Elevated concentrations of systemic complement proteins were found in patients with iAMD and nAMD. Decreased Creg expression levels were found in patients with nAMD. Partially responding nAMD patients had a dysregulated complement system and Cregs compared to good responders.},
}
@article {pmid39486499,
year = {2024},
author = {Ji, J and Xiong, C and Yang, H and Jiang, Z and Zhang, Y and Wang, X and Yu, T and Li, Q and Zhu, S and Zhou, Y},
title = {The aryl hydrocarbon receptor: A crucial mediator in ocular disease pathogenesis and therapeutic target.},
journal = {Experimental eye research},
volume = {249},
number = {},
pages = {110144},
doi = {10.1016/j.exer.2024.110144},
pmid = {39486499},
issn = {1096-0007},
mesh = {*Receptors, Aryl Hydrocarbon/metabolism ; Humans ; *Eye Diseases/metabolism/drug therapy ; Animals ; Signal Transduction/physiology ; Retinal Pigment Epithelium/metabolism/pathology ; },
abstract = {The aryl hydrocarbon receptor (AHR) is a pivotal nuclear receptor involved in mediating cellular responses to a wide range of environmental pollutants and endogenous ligands. AHR plays a central role in regulating essential physiological processes, including xenobiotic metabolism, immune response modulation, cell cycle control, tumorigenesis, and developmental events. Recent studies have identified AHR as a critical mediator and a potential therapeutic target in the pathogenesis of ocular diseases. This review provides a thorough analysis of the various functions of AHR signalling in the ocular environment, with a specific emphasis on its effects on the retina, retinal pigment epithelium (RPE), choroid, and cornea. We provide a detailed discussion on the molecular mechanisms through which AHR integrates environmental and endogenous signals, influencing the development and progression of age-related macular degeneration (AMD), retinitis pigmentosa, uveitis, and other major ocular disorders. Furthermore, we evaluate the therapeutic potential of modulating AHR activity through novel ligands and agonists as a strategy for treating eye diseases. Understanding the molecular mechanisms of AHR in ocular tissues may facilitate the development of AHR-targeted therapies, which is crucial for addressing the pressing clinical demand for novel treatment strategies in ocular diseases.},
}
@article {pmid39485049,
year = {2025},
author = {John, R and Williams, G and Morgan, T and George, MR and Reynolds, R and Acton, JH},
title = {The unmet need for certification of vision impairment for people accessing a national primary care-based low vision rehabilitation service.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {1},
pages = {308-314},
pmid = {39485049},
issn = {1475-1313},
mesh = {Humans ; *Primary Health Care/standards ; Male ; Female ; *Vision, Low/rehabilitation/epidemiology ; Aged ; *Visual Acuity ; Aged, 80 and over ; Middle Aged ; Certification ; Health Services Needs and Demand ; Persons with Visual Disabilities/statistics &amp; numerical data/rehabilitation ; United Kingdom/epidemiology ; Health Services Accessibility/statistics &amp; numerical data ; Macular Degeneration/complications ; },
abstract = {BACKGROUND: The certificate of vision impairment has an important role in enabling access to support for people with vision impairment (VI) and the provision of epidemiological data regarding sight loss. However, the rates of certification may not accurately reflect the number of people living with certifiable VI.<br><br>METHODS: Observational data from a national primary care low vision rehabilitation service between 1 April 2021 and 31 March 2022 were analysed. Descriptive statistics were used to describe the certification status of patients with certifiable VI. For patients with age-related macular degeneration (AMD) and best-corrected visual acuity of 6/60 or worse, logistic regression was undertaken to assess the effects of patient characteristics on certification status.<br><br>RESULTS: For patients with AMD and certifiable levels of visual acuity, 41.00% (n&#x2009;=&#x2009;426) were not certified. The reported certification was 60.09% (n&#x2009;=&#x2009;256) and 58.24% (n&#x2009;=&#x2009;357) for neovascular AMD and atrophic AMD, respectively. Existing patients of the service were 3.87 times more likely to be certified than new patients (OR 3.87, 95% CI 2.7-5.4). Increasing age (OR 1.02, 95% CI 1.004-1.038) and decreasing visual acuity (OR 0.62, 95% CI 0.50-0.78) were associated with an increased likelihood of certification.<br><br>CONCLUSION: A significant number of patients live with certifiable vision impairment but do not access certification. Policy changes in Wales now enable patients with bilateral atrophic AMD to access certification within the primary care setting. Given the unmet need, consideration should be given to primary care certification in the rest of the UK, and in Wales, the potential to expand the scope of conditions.},
}
@article {pmid39482884,
year = {2025},
author = {Lim, Y and Kang, TK and Kim, MI and Kim, D and Kim, JY and Jung, SH and Park, K and Lee, WB and Seo, MH},
title = {Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {12},
number = {1},
pages = {e2406018},
pmid = {39482884},
issn = {2198-3844},
support = {2E33311//Korea Institute of Science and Technology/ ; 2021R1C1C1003843//National Research Foundation of Korea/ ; },
mesh = {*Toll-Like Receptors/metabolism/immunology ; Animals ; Mice ; *Peptides/metabolism/pharmacology ; *Receptors, Interleukin-1/metabolism ; Signal Transduction/drug effects ; Humans ; Peptide Library ; },
abstract = {Toll-like receptors (TLRs) are critical regulators of the immune system, and altered TLR responses lead to a variety of inflammatory diseases. Interference of intracellular TLR signaling, which is mediated by multiple Toll/interleukin-1 receptor (TIR) domains on all TLRs and TLR adapters, is an effective therapeutic strategy against immune dysregulation. Peptides that inhibit TIR-TIR interactions by fragmenting interface residues have potential as therapeutic decoys. However, a systematic method for discovering TIR-targeting moieties has been elusive, limiting exploration of the vast, unsequenced space of the TIR domain family. A comprehensive parallel screening method is developed to uncover novel TIR-binding peptides derived from previously unexplored surfaces on a wide range of TIR domains. A large peptide library is constructed, named TIR surfacesome, by tiling surface sequences of the large TIR domain family and screening against MAL[TIR] and MyD88[TIR], TIRs of two major TLR adaptor proteins, resulting in the discovery of hundreds of TIR-binding peptides. The selected peptides inhibited TLR signaling and demonstrated anti-inflammatory effects in macrophages, and therapeutic potential in mouse inflammatory models. This approach may facilitate the development of TLR-targeted therapeutics.},
}
@article {pmid39480444,
year = {2024},
author = {Paudel, N and Brady, L and Stratieva, P and Galvin, O and Lui, B and Van den Brande, I and Malkowski, JP and Rebeira, M and MacAllister, S and O'Riordan, T and Daly, A},
title = {Economic Burden of Late-Stage Age-Related Macular Degeneration in Bulgaria, Germany, and the US.},
journal = {JAMA ophthalmology},
volume = {142},
number = {12},
pages = {1123-1130},
pmid = {39480444},
issn = {2168-6173},
mesh = {Humans ; Female ; Germany/epidemiology ; Male ; Aged ; *Cost of Illness ; United States/epidemiology ; Middle Aged ; *Health Care Costs/statistics &amp; numerical data ; Bulgaria/epidemiology ; Prevalence ; Aged, 80 and over ; Geographic Atrophy/economics/epidemiology ; Wet Macular Degeneration/economics/epidemiology ; Quality of Life ; Quality-Adjusted Life Years ; Macular Degeneration/economics/epidemiology ; },
abstract = {IMPORTANCE: Age-related macular degeneration (AMD) is a highly prevalent and debilitating retinal condition that affects more than 200 million people globally, with the severe late-stage forms-neovascular AMD (nAMD) and geographic atrophy (GA)-affecting more than 11 million people globally. However, much is unknown about the economic burden of the disease.<br><br>OBJECTIVE: To estimate the economic burden associated with late-stage AMD in Bulgaria, Germany, and the US at the societal level.<br><br>This study used the prevalence approach cost-of-illness economic modeling to estimate costs attributable to late-stage AMD. Data on health care resource utilization, well-being, and productivity were obtained via primary data collection. Additional data required for the model were sourced from available published literature. Data were collected from January 2021 to March 2022, and analyzed from April to July 2022. Participants older than 50 years residing in Bulgaria, Germany, and the US who were diagnosed with late-stage AMD (nAMD or any form of GA) in 1 or both eyes and caregivers who care for people diagnosed with late-stage AMD were recruited through ophthalmological clinics in Bulgaria and Germany and via online newsletters and social media in the US.<br><br>MAIN OUTCOMES AND MEASURES: The main outcomes were direct medical costs (disease-related health care expenditures), indirect medical costs (care support and assistive technology), well-being cost (loss of well-being), and productivity cost (loss in productivity due to the diseases for both patient and caregivers).<br><br>RESULTS: Of the 128 individuals with late-stage AMD in this study, 80 (62%) were female, and 120 (94%) were aged 60 years or older. Of the 61 caregivers, 43 (70%) were female and 55 (91%) were aged 45 years or older. Estimated per-annum total costs attributable to late-stage AMD were &#x20ac;449.5 million ($512.5 million) in Bulgaria, &#x20ac;7.6 billion ($8.6 billion) in Germany, and &#x20ac;43.2 billion ($49.4 billion) in the US. Across all countries, 10% to 13% of the total cost incurred was attributed to direct medical costs. In Germany and Bulgaria, the biggest contributor to the total economic burden was reduced well-being (67% and 76%, respectively), whereas in the US, loss of productivity (42%) was the biggest contributor.<br><br>CONCLUSIONS AND RELEVANCE: The findings of this study indicate a substantial burden of late-stage AMD on patients and caregivers in the US, Germany, and Bulgaria. Across the 3 countries, reduced well-being and loss of productivity were relatively large contributors to the total economic burden. Implementing measures to reduce AMD incidence, delay disease progression, and alleviate humanistic burden may help reduce the economic burden of late-stage AMD.},
}
@article {pmid39479233,
year = {2024},
author = {Scheepers, R and Levi, NL and Araujo, RP},
title = {A distributed integral control mechanism for regulation of cholesterol concentration in the human retina.},
journal = {Royal Society open science},
volume = {11},
number = {10},
pages = {240432},
pmid = {39479233},
issn = {2054-5703},
abstract = {Tight homeostatic control of cholesterol concentration within the complex tissue microenvironment of the retina is the hallmark of a healthy eye. By contrast, dysregulation of biochemical mechanisms governing retinal cholesterol homeostasis likely contributes to the aetiology and progression of age-related macular degeneration (AMD). While the signalling mechanisms maintaining cellular cholesterol homeostasis are well-studied, a systems-level description of molecular interactions regulating cholesterol balance within the human retina remains elusive. Here, we provide a comprehensive overview of all currently-known molecular-level interactions involved in cholesterol regulation across the major compartments of the human retina, encompassing the retinal pigment epithelium (RPE), photoreceptor cell layer, Müller cell layer and Bruch's membrane. We develop a comprehensive chemical reaction network (CRN) of these interactions, involving 71 molecular species, partitioned into 10 independent subnetworks. These subnetworks collectively ensure robust homeostasis of 14 forms of cholesterol across distinct retinal cellular compartments. We provide mathematical evidence that three independent antithetic integral feedback controllers tightly regulate ER cholesterol in retinal cells, with additional independent mechanisms extending this regulation to other forms of cholesterol throughout the retina. Our novel mathematical model of retinal cholesterol regulation provides a framework for understanding the mechanisms of cholesterol dysregulation in diseased eyes and for exploring potential therapeutic strategies.},
}
@article {pmid39477959,
year = {2024},
author = {Jarocki, M and Turek, K and Saczko, J and Tarek, M and Kulbacka, J},
title = {Lipids associated with autophagy: mechanisms and therapeutic targets.},
journal = {Cell death discovery},
volume = {10},
number = {1},
pages = {460},
pmid = {39477959},
issn = {2058-7716},
support = {2021/41/B/ST5/02233//Narodowe Centrum Nauki (National Science Centre)/ ; },
abstract = {Autophagy is a molecular process essential for maintaining cellular homeostasis, with its impairment or dysregulation linked to the progression of various diseases in mammals. Specific lipids, including phosphoinositides, sphingolipids, and oxysterols, play pivotal roles in inducing and regulating autophagy, highlighting their significance in this intricate process. This review focuses on the critical involvement of these lipids in autophagy and lipophagy, providing a comprehensive overview of the current understanding of their functions. Moreover, we delve into how abnormalities in autophagy, influenced by these lipids, contribute to the pathogenesis of various diseases. These include age-related conditions such as cardiovascular diseases, neurodegenerative disorders, type 2 diabetes, and certain cancers, as well as inflammatory and liver diseases, skeletal muscle pathologies and age-related macular degeneration (AMD). This review aims to highlight function of lipids and their potential as therapeutic targets in treating diverse human pathologies by elucidating the specific roles of phosphoinositides, sphingolipids, and oxysterols in autophagy.},
}
@article {pmid39477789,
year = {2024},
author = {Abbott, CJ and Guymer, RH},
title = {Emerging treatments for geographic atrophy and the impact on clinical management of age-related macular degeneration.},
journal = {Clinical &amp; experimental optometry},
volume = {107},
number = {8},
pages = {779-787},
doi = {10.1080/08164622.2024.2361752},
pmid = {39477789},
issn = {1444-0938},
mesh = {Humans ; *Geographic Atrophy/therapy/diagnosis ; *Macular Degeneration/therapy/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment in people over 50 years of age and has a great impact on quality of life as it affects central vision. Although there have been treatments available for the neovascular form of late AMD for decades, until now there have not been treatments available for the atrophic form of late AMD - geographic atrophy (GA). Recently, treatments acting on the complement pathway have been approved by the United States Food and Drug Administration, with other jurisdictions such as Australia considering their approval. Furthermore, there are many more potential treatments for GA currently in clinical trials. However, unlike the treatments for neovascular AMD, where clinicians have treated virtually all patients presenting with exudation, the decision to treat those with GA will be more nuanced and individualised. Longitudinal retinal imaging will be one important asset that will help tremendously when counselling patients, as through these images, the growth pattern of the atrophy can be determined. Even without individual prior imaging history, there are other imaging clues to help predict growth rates and threats to the fovea, and hence imminent vision loss. Optometrists have a critical role in this new era where GA treatments will be available, as they are often the first to have contact with GA patients. Insightful, well-informed counselling and appropriate referral for those seeking more information on potential treatment to confirm the diagnosis and perform baseline imaging at a location likely to undertake any future treatment will ensure that appropriate patients have had the best workup to be individually managed once these treatments arrive in Australia.},
}
@article {pmid39475629,
year = {2024},
author = {Flavin, B and Schimel, A and Contreras, Z and Shannon, MH and Bioc, J},
title = {Stakeholder insights on cost, quality, and incorporating patient voice in managed care decisions on neovascular (wet) age-related macular degeneration: Findings from the AMCP Market Insights program.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {30},
number = {11-a Suppl},
pages = {S1-S9},
pmid = {39475629},
issn = {2376-1032},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy/economics ; *Managed Care Programs/economics ; *Angiogenesis Inhibitors/economics/therapeutic use/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Stakeholder Participation ; Cost-Benefit Analysis ; Quality of Health Care ; },
abstract = {Wet age-related macular degeneration (AMD) is an acquired degeneration of the retina that can lead to central vision impairment. It is primarily treated with intravitreal injections of vascular endothelial growth factor inhibitors. Although vascular endothelial growth factor inhibitors can effectively prevent progression of vision loss in many patients, they require ongoing regular administration and are therefore associated with considerable treatment burden. To gain insights into the impact of wet AMD and its treatment, AMCP convened an expert panel of managed care stakeholders in April 2024 through its Market Insights program. Key issues related to wet AMD identified by participants included cost and affordability, provider-related considerations, biosimilar adoption, measuring and improving quality, and incorporating the patient voice. Suggested payer best practices related to these issues in wet AMD also emerged from the discussion.},
}
@article {pmid39474210,
year = {2024},
author = {Pericak, JM and Chin, EK and Almeida, DRP},
title = {Vitamin a Deficiency in an Elderly Patient: A Diagnostic Challenge in the Age of AMD.},
journal = {International medical case reports journal},
volume = {17},
number = {},
pages = {879-881},
pmid = {39474210},
issn = {1179-142X},
abstract = {The presentation of vitamin A deficiency (VAD)-induced ocular complications can be challenging to diagnose in elderly patients, particularly due to the overlap with age-related macular degeneration (AMD) symptoms. This case report details the presentation, diagnosis, and management of an 88-year-old female with vision loss, highlighting the ocular manifestations of presumed VAD. Despite vitamin A levels being at the lower end of the normal range, the patient's symptoms and spectral domain optical coherence tomography (SD-OCT) findings suggested insufficient levels, leading to thinning of the outer nuclear layer. This case underscores the necessity of considering VAD in differential diagnoses of unexplained vision impairment, particularly in individuals with a history of intestinal malabsorption, while also emphasizing the importance of distinguishing VAD from AMD in elderly patients.},
}
@article {pmid39474125,
year = {2024},
author = {Lee, S and Park, JY and Hong, HK and Son, JY and Kim, B and Chung, JY and Woo, SJ and Park, KD},
title = {Intravitreal long-term sustained ranibizumab delivery using injectable microgel-embedded hydrogel.},
journal = {Asian journal of pharmaceutical sciences},
volume = {19},
number = {5},
pages = {100947},
pmid = {39474125},
issn = {2221-285X},
abstract = {Retinal vascular disease is the leading cause of visual impairment. Although intravitreal drug injections are the most suitable approach for addressing retinal disorders, existing clinical treatments necessitate repeated administration, imposing a substantial burden on patients with various intraocular complications. This study introduces an injectable and biodegradable hyaluronan microgel (Hm)-embedded gelatin-poly(ethylene glycol)-tyramine hydrogel (HmGh) designed for sustained intravitreal ranibizumab (RBZ) delivery to reduce patient burden and minimize the side effects associated with frequent injections. Hm exhibited a controlled RBZ loading capacity and release profile. HmGh effectively controlled the initial burst release and overall release profile. Cytocompatibility and cellular drug efficacy were also demonstrated. In an animal study, HmGh maintained RBZ concentrations in the vitreous and retina for >120 d. Pharmacokinetic studies showed that the half-life of RBZ-loaded HmGh in the vitreous and retina was 2.55 and 2.05 times longer than that of RBZ-loaded Hm, respectively, and 9.58 and 38.46 times longer than that of RBZ solution, respectively. Importantly, the initial RBZ elimination from HmGh to the aqueous humor was significantly reduced compared to that from the Hm and RBZ solutions. Intraocular degradation and safety were comprehensively evaluated using fundus imaging and histological analyses. In conclusion, this injectable microgel-embedded hydrogel formulation is a promising prolonged drug delivery system for treating various posterior segment eye diseases.},
}
@article {pmid39472501,
year = {2025},
author = {Broadbent, E and Künzel, SH and Pfau, M and Schmitz-Valckenberg, S and Fleckenstein, M},
title = {Age-related macular degeneration: natural history revisited in geographic atrophy.},
journal = {Eye (London, England)},
volume = {39},
number = {2},
pages = {217-227},
pmid = {39472501},
issn = {1476-5454},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY034965/EY/NEI NIH HHS/United States ; R01EY033365//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01EY034965//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; },
mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis ; Disease Progression ; Quality of Life ; *Macular Degeneration/physiopathology ; Visual Acuity/physiology ; Tomography, Optical Coherence ; Prognosis ; },
abstract = {Progression of geographic atrophy varies significantly based on individual and lesion characteristics. Much research has strived to understand prognostic indicators of lesion progression over time, yet integrating findings to date may pose a challenge to clinicians. This review strives to synthesize current knowledge on genetic, behavioral, structural, and functional factors that influence geographic atrophy across the lifetime. Further, it highlights how vision-related quality of life allows for a more holistic appraisal of the impact of geographic atrophy on everyday functioning. The ultimate aim of this paper is to aid clinicians in counseling patients on medical management as well as providing accurate disease prognostication tailored to the individual patient.},
}
@article {pmid39468037,
year = {2024},
author = {Nouri, N and Gussler, BH and Stockwell, A and Truong, T and Kang, GJ and Browder, KC and Malato, Y and Sene, A and Van Everen, S and Wykoff, CC and Brown, D and Fu, A and Palmer, JD and Lima de Carvalho, JR and Ullah, E and Al Rawi, R and Chew, EY and Zein, WM and Guan, B and McCarthy, MI and Hofmann, JW and Chaney, SY and Jasper, H and Yaspan, BL},
title = {SLC16A8 is a causal contributor to age-related macular degeneration risk.},
journal = {NPJ genomic medicine},
volume = {9},
number = {1},
pages = {50},
pmid = {39468037},
issn = {2056-7944},
abstract = {Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter. First, in an unbiased, genome-wide analysis of rare coding variants we show multiple SLC16A8 rare variants are associated with AMD risk, corroborating previous borderline significant reports from AMD rare variant studies. Second, we report a novel SLC16A8 mutation in a three-generation family with early onset macular degeneration. Finally, mis-expression in multiple model organisms shows functional and anatomic retinal consequences. This study highlights the important role for SLC16A8 and lactate regulation towards outer retina/RPE health and highlights a potential new therapeutic opportunity for the treatment of AMD.},
}
@article {pmid39467145,
year = {2024},
author = {Guo, Y and Chen, S and Guan, W and Xu, N and Zhu, L and Du, W and Liu, Z and Fong, HKW and Huang, L and Zhao, M},
title = {Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {38},
number = {20},
pages = {e70135},
pmid = {39467145},
issn = {1530-6860},
support = {82171060//the National Natural Science Foundation of China/ ; 2020YFC2008200//the National Key Research and Development Program of China/ ; 2020YFC2008203//the National Key Research and Development Program of China/ ; },
mesh = {Animals ; Male ; Mice ; Diet, High-Fat/adverse effects ; *Macular Degeneration/metabolism/pathology/genetics/etiology ; Mice, Inbred C57BL ; *Oxidative Stress ; Protein Kinases/metabolism/genetics ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Retina/metabolism/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Signal Transduction ; *Ubiquitin-Protein Ligases/metabolism/genetics ; },
abstract = {The intake of high dietary fat has been correlated with the progression of age-related macular degeneration (AMD), affecting the function of the retinal pigment epithelium through oxidative stress. A high-fat diet (HFD) can lead to lipid metabolism disorders, excessive production of circulating free fatty acids, and systemic inflammation by aggravating the degree of oxidative stress. Deletion of the retinal G-protein-coupled receptor (RGR-d) has been identified in drusen. In this study, we investigated how the RGR-d exacerbates AMD-like changes under oxidative stress, both in vivo and in vitro. Fundus atrophy became evident, at 12 months old, particularly in the RGR-d + HFD group, and fluorescence angiography revealed narrower retinal vessels and a reduced perfusion area in the peripheral retina. Although rod electroretinography revealed decreasing trends in the a- and b-wave amplitudes in the RGR-d + HFD group at 12 months, the changes were not statistically significant. Mice in the RGR-d + HFD group showed a significantly thinner and more fragile retinal morphology than those in the WT + HFD group, with disordered and discontinuous pigment distribution in the RGR-d + HFD mice. Transmission electron microscopy revealed a thickened Bruch's membrane along the choriocapillaris endothelial cell wall in the RGR-d + HFD mice, and the outer nuclear layer structure appeared disorganized, with reduced nuclear density. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated significantly lower levels of 25(OH)-vitamin D3 metabolites in the RGR-d + HFD group. Under oxidative stress, RGR-d localized to the mitochondria and reduced the levels of the PINK1-parkin pathway. RGR-d mice fed an HFD were used as a new animal model of dry AMD. Under high-fat-induced oxidative stress, RGR-d accumulated in the mitochondria, disrupting normal mitophagy and causing cellular damage, thus exacerbating AMD-like changes both in vivo and in vitro.},
}
@article {pmid39466057,
year = {2024},
author = {Xu, S and Li, J and Long, K and Wang, W},
title = {Reactive Oxygen Species Responsive Supramolecular Prodrug Eyedrops for the Treatment of Choroidal Neovascularization.},
journal = {Nano letters},
volume = {24},
number = {46},
pages = {14584-14593},
doi = {10.1021/acs.nanolett.4c02576},
pmid = {39466057},
issn = {1530-6992},
mesh = {*Choroidal Neovascularization/drug therapy/pathology ; *Prodrugs/chemistry/pharmacology/therapeutic use ; Animals ; Mice ; *Reactive Oxygen Species/metabolism ; *Ophthalmic Solutions/administration &amp; dosage/pharmacology ; Angiogenesis Inhibitors/pharmacology/chemistry/therapeutic use/administration &amp; dosage/pharmacokinetics ; Humans ; Disease Models, Animal ; Cyclodextrins/chemistry ; Polyethylene Glycols/chemistry ; },
abstract = {Choroidal neovascularization (CNV) represents a hallmark of neovascular fundus diseases, including age-related macular degeneration and diabetic retinopathy. Traditional eyedrops have encountered formidable challenges in treating CNV, primarily due to their extremely poor intraocular bioavailability and potential adverse off-target effects. Herein, an ocular-permeable supramolecular prodrug eyedrop (Di-DAS/P-PCD) has been developed for the on-demand delivery of antiangiogenic agents in the oxidative microenvironment of CNV. The eyedrop nanoformulation is composed of cell-penetrating peptide-modified PEGylated cyclodextrin (P-PCD) and reactive oxygen species (ROS)-sensitive antiangiogenic dasatinib prodrug Di-DAS. In a laser-induced CNV mouse model, daily instillation of Di-DAS/P-PCD has achieved remarkable penetration into the choroid and significantly suppressed CNV growth while exhibiting a good biocompatibility profile. Our results highlight the potential of the supramolecular prodrug eyedrops as a versatile approach for the targeted treatment of CNV and other neovascular eye disorders.},
}
@article {pmid39465270,
year = {2024},
author = {Yu, E and Kim, H and Park, H and Hong, JH and Jin, J and Song, Y and Woo, JM and Min, JK and Yun, J},
title = {Targeting the VEGFR2 signaling pathway for angiogenesis and fibrosis regulation in neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {25682},
pmid = {39465270},
issn = {2045-2322},
support = {NRF-2022R1F1A1069431//The national research foundation of Korea/ ; MRC, 2017R1A5A2015541//The national research foundation of Korea/ ; UUH-2020-07//Ulsan University Hospital/ ; 20182MFDS425//The Ministry of Food and Drug Safety of Korea/ ; 22214MFDS252//The Ministry of Food and Drug Safety of Korea/ ; 23212MFDS217//The Ministry of Food and Drug Safety of Korea/ ; },
mesh = {*Vascular Endothelial Growth Factor Receptor-2/metabolism ; Humans ; Animals ; *Signal Transduction/drug effects ; Mice ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; *Pyridines/pharmacology ; *Fibrosis ; *Macular Degeneration/metabolism/pathology/drug therapy ; Male ; Vascular Endothelial Growth Factor A/metabolism ; Female ; Disease Models, Animal ; Neovascularization, Pathologic/metabolism/drug therapy ; Aged ; Cell Line ; Angiogenesis ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is characterized by abnormal blood vessel growth from the choroid, leading to complications and eventual blindness. Despite anti-VEGF therapy, subretinal fibrosis remains a major concern, as VEGF/VEGF receptor-2 (VEGFR2) signaling can contribute to both angiogenesis and fibrosis. For the identification of the aqueous humor proteome, we performed liquid chromatography with tandem mass spectrometry analysis. To investigate the potential therapeutic effects of targeting the VEGF signaling pathway using apatinib, a highly selective VEGFR2 tyrosine kinase inhibitor, this study employed in vitro (THP-1 conditioned media-treated ARPE-19 cells) and in vivo (laser-induced choroidal neovascularization mouse) models of nAMD. This study revealed elevated VEGFR2 protein levels in the aqueous humor of nAMD patients, suggesting a potential target to mitigate neovascularization and fibrosis in nAMD. Apatinib effectively reduced VEGFA and αSMA levels in both in vitro and in vivo models. Moreover, apatinib showed improvement in laser-induced subretinal hyper-reflective lesions. The action mechanism was linked to the inhibition of VEGFR2 activation, leading to the suppression of both angiogenesis and fibrosis through the downregulation of STAT3 phosphorylation. Therefore, the VEGFR2 signaling pathway appears to play a central role in the development of nAMD by regulating both angiogenesis and fibrosis.},
}
@article {pmid39464766,
year = {2024},
author = {Loscos-Giménez, I and Rego-Lorca, D and Bassaganyas-Vilarrasa, F and Crespí-Vilimelis, J and Díaz-Cascajosa, J and Segarra, JIV},
title = {New prefilled syringe aflibercept design. A cause of symptomatic IOP spike after aflibercept PFS?.},
journal = {Romanian journal of ophthalmology},
volume = {68},
number = {3},
pages = {219-224},
pmid = {39464766},
issn = {2501-2533},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Syringes ; *Intraocular Pressure/physiology/drug effects ; Male ; *Intravitreal Injections ; Female ; *Ocular Hypertension/physiopathology/diagnosis/drug therapy/chemically induced ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Aged ; Middle Aged ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Equipment Design ; Aged, 80 and over ; Retrospective Studies ; Tonometry, Ocular ; },
abstract = {OBJECTIVE: To describe ocular hypertension cases after using a new aflibercept prefilled syringe and to assess the main characteristics of these eyes and their possible association with intraocular pressure (IOP) changes.<br><br>METHODS: Case series. We reported all the cases of ocular hypertension following aflibercept prefilled syringes (PFS) treatment in our department between April 2021 and December 2023.<br><br>RESULTS: A total of 4183 eyes were treated with aflibercept PSF. Thirteen transitory IOP elevations were observed immediately after injection (0.3%). Two eyes had an IOP between 30-35 mmHg, five eyes had an IOP between 36-55 mmHg and three eyes had an IOP > 56 mmHg. The mean IOP was 45.5 mmHg&#xb1;11.33. Only six eyes needed anterior chamber paracentesis (37.5%). The other patients were treated conservatively (ocular massage and/or IOP-lowering drops). The mean IOP after treatment was 15.71 mmHg&#xb1;7.20. Visual acuity improved after treatment in all the patients.<br><br>DISCUSSION: Compared with other injectors, reports have indicated a higher incidence of moderate and severe IOP spikes with aflibercept PSF. The European Medicine Agency (EMA) has associated this significant increase with incorrect syringe handling, leading to higher injection volumes. Although plunger misalignment seems to play a role in the IOP spikes, some other characteristics of this new injector could play a role. Factors such as syringe diameter, plunger alignment, and injection force may contribute to this issue. The reason some authors found no significant differences in IOP elevation after IVI, with aflibercept PFS, could be due to variations in patient characteristics, which may also play an important role in post-IVI pressure changes.<br><br>CONCLUSIONS: Intraocular pressure spikes after aflibercept PFS can be explained by injector characteristics. The PFS of aflibercept has a domed plunger. Incorrect alignment between the base of the plunger and the black dosing line could cause an increase in the injected volume. Furthermore, the wider syringe diameter of aflibercept PFS could imply a larger injection force, increasing the risk of IOP elevation. Patient characteristics, such as previous VPP, axial length, or glaucoma history, may also play a role. Further studies are required to develop an ideal intravitreal syringe.},
}
@article {pmid39464028,
year = {2024},
author = {Ortega, AJ and Daniel, S and Renwick, M and Kambhampati, P and Thompson, KN and Collier, GE and Baker, EL and Zaki, H and Hulleman, JD},
title = {Genetic removal of Nlrp3 protects against sporadic and R345W Efemp1-induced basal laminar deposit formation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39464028},
issn = {2692-8205},
support = {R01 DK125352/DK/NIDDK NIH HHS/United States ; R01 DK128031/DK/NIDDK NIH HHS/United States ; R01 EY027785/EY/NEI NIH HHS/United States ; },
abstract = {Chronic, unresolved inflammation has long been speculated to serve as an initiating and propagating factor in numerous neurodegenerative diseases, including a leading cause of irreversible blindness in the elderly, age-related macular degeneration (AMD). Intracellular multiprotein complexes called inflammasomes in combination with activated caspases facilitate production of pro-inflammatory cytokines such as interleukin 1 beta. Specifically, the nucleotide-binding oligomerization (NOD)-like receptor protein 3 (NLRP3) has received heightened attention due to the wide range of stimuli to which it can respond and its potential involvement in AMD. In this study, we directly tested the role of Nlrp3 and its downstream effector, caspase 1 (Casp1) in mediating early AMD-like pathology (i.e., basal laminar deposits [BLamDs]) in wild-type (WT) mice and the Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) mouse model (p.R345W mutation in Efemp1). Compared to aged-matched controls, R345W[+/+] knockin mice demonstrated increased Muller cell gliosis, subretinal Iba-1[+] microglial cells, higher Nlrp3 immunoreactivity in the retina, as well as significant transcriptional upregulation of complement component 3, Nlrp3, pro-Il1b, pro-caspase-1, and tissue inhibitor of matrix metalloproteinase 3 in the retinal pigmented epithelium (RPE)/choroid. These findings were accompanied by an age-related increase in BLamD formation in the R345W[+/+] mice. Genetic elimination of either Nlrp3 or Casp1 significantly reduced both the size and coverage of BLamDs in the R345W[+/+] background, highlighting an important and underappreciated pathway that could affect ML/DHRD onset and progression. Moreover, Nlrp3 knockout reduced spontaneous, idiopathic BLamDs in WT mice, suggesting translatability of our findings not only to rare inherited retinal dystrophies, but also potentially to AMD itself.},
}
@article {pmid39463170,
year = {2024},
author = {Yan, A and La Rosa, A and Chhablani, PP and Chhablani, J},
title = {Caffeine and Vision: Effects on the Eye.},
journal = {Turkish journal of ophthalmology},
volume = {54},
number = {5},
pages = {291-300},
pmid = {39463170},
issn = {2149-8709},
mesh = {Humans ; *Caffeine/adverse effects ; Intraocular Pressure/physiology/drug effects ; Central Nervous System Stimulants/adverse effects ; Eye Diseases/physiopathology ; Vision, Ocular/physiology/drug effects ; },
abstract = {Caffeine, commonly found in coffee and tea, affects various aspects of eye health as it blocks adenosine receptors, impacting tear production, intraocular pressure, macular perfusion, and choroidal thickness. However, its connection with eye conditions like glaucoma and cataracts remains uncertain due to conflicting research findings. Some studies suggest potential benefits for cataracts, while others warn against frequent caffeine intake in glaucoma and surgical scenarios due to possible increases in intraocular pressure. Conflicting evidence also exists regarding its effects on dry eye, macular degeneration, myopia/hyperopia, diabetic retinopathy, retinopathy of prematurity, and central serous retinopathy. Caffeine does not seem to be a risk factor for dry eye, although studies have shown that caffeine may offer protection against wet age-related macular degeneration, and the metabolite 7-methylxanthine could be a more promising treatment for myopia. Moreover, caffeine can potentially cause tremors and might hinder surgical performance, especially in less experienced surgeons. Recommendations from experts vary, highlighting the need for further research to fully understand how caffeine affects the eye. Individuals genetically predisposed to glaucoma should be cautious due to the possibility of clinically significant elevations in intraocular pressure with caffeine consumption. For delicate procedures like microsurgery, where tremors can be detrimental, caution should be exercised with caffeine. This review underscores the importance of additional studies to provide clearer insights and prudent recommendations regarding caffeine's impact on eye health.},
}
@article {pmid39463155,
year = {2024},
author = {Wang, Y and Lv, Z and Chen, Y and Cen, X and Zhang, H and Chen, D},
title = {A high-fat plus high-sucrose diet induces age-related macular degeneration in an experimental rabbit model.},
journal = {Disease models &amp; mechanisms},
volume = {17},
number = {11},
pages = {},
pmid = {39463155},
issn = {1754-8411},
support = {82101154//National Natural Science Foundation of China/ ; 81870665//National Natural Science Foundation of China/ ; 82171063//National Natural Science Foundation of China/ ; 2021YFS0212, 2024YFFK0301//Science and Technology Department of Sichuan Province/ ; //West China Hospital, Sichuan University/ ; },
mesh = {Animals ; Rabbits ; *Diet, High-Fat/adverse effects ; Male ; *Disease Models, Animal ; *Macular Degeneration/pathology/etiology ; Complement C3/metabolism ; Sucrose/adverse effects ; Retina/pathology/metabolism ; Electroretinography ; Retinal Drusen/pathology ; Lipids/blood ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness. Metabolic disorders and diets are risk factors. We compared lipid profiles and retinal phenotypes with long-term feeding of four diets in male Chinchilla rabbits. Animals were fed a normal diet (ND), high-fat diet (HFD), high-sucrose diet (HSD) or a high-fat plus high-sucrose diet (HFSD) for 6 months. Eyes were examined using multimodal imaging modalities and electroretinograms. Retinal sections were analyzed using H&amp;E staining, Toluidine Blue staining, immunostaining and transmission electron microscopy. Lipids and complement C3 protein (C3) in serum or aqueous humor were measured. RNA sequencing was performed to evaluate the retinal transcriptomes. HFD and HSD had minor effects on lipid profiles but, when fed concomitantly, synergistically induced severe dyslipidemia. None of the four diets caused obesity. HFSD induced retinal lesions, such as reticular pseudodrusen (RPDs) and other pigmentary abnormalities. RPD-like lesions were mainly lipid droplets around cells of the retinal pigment epithelium. HFSD also induced elevated levels of ocular C3 and reduced the density of retinal vessels. In conclusion, HFD and HSD can - when combined - induce normal-weight dyslipidemia and RPD-like retinal lesions. HFSD-fed male Chinchilla rabbits are a good model of early AMD.},
}
@article {pmid39462007,
year = {2024},
author = {Lishinsky-Fischer, N and Misgav, K and Chowers, I and Tiosano, L and Shwartz, Y and Levy, J},
title = {Association of subretinal drusenoid deposits and cardiovascular disease.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {25569},
pmid = {39462007},
issn = {2045-2322},
support = {#3485/19//Israel Science Foundation/ ; #3485/19//Israel Science Foundation/ ; #3485/19//Israel Science Foundation/ ; #3485/19//Israel Science Foundation/ ; },
mesh = {Humans ; Female ; *Cardiovascular Diseases/complications ; Male ; Aged ; *Retinal Drusen/diagnostic imaging/pathology ; *Macular Degeneration/pathology/diagnostic imaging/complications ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Aged, 80 and over ; Middle Aged ; },
abstract = {The presence of subretinal drusenoid deposits (SDDs) in patients with age-related macular degeneration (AMD) appears to be correlated with cardiovascular disease (CVD) and may serve as a useful tool for predicting certain forms of CVD. Here, we tested this hypothesis by examining whether patients with AMD with SDDs are more likely to have a cardiovascular-related condition and/or undergo a cardiovascular procedure. This is a retrospective cohort study. We included a total of 597 patients with AMD either with SDDs (n = 332) or without SDDs (n = 265). All patients underwent spectral-domain optical coherence tomography (SD-OCT). The SD-OCT scans were annotated by masked, experienced graders. We also extracted data from the patients' electronic medical records (EMRs), including patient demographics, cardiovascular diagnoses, and CVD-related procedures based on ICD-9 codes. AMD patients with SDDs were more likely to be diagnosed with CVD or undergo a cardiovascular procedure compared to AMD patients without SDDs, particularly percutaneous transluminal coronary angioplasty (PTCA; OR 2.73, 95% CI [1.21, 6.13], p = 0.02). Multivariate analysis confirmed the association between the presence of SDDs and a background of PTCA in the presence of other covariates. These data suggest that the presence of SDDs in patients with AMD correlates with certain severe cardiovascular conditions; SDDs and CVD may share common pathogenic pathways.},
}
@article {pmid39461425,
year = {2025},
author = {Wongchaisuwat, N and Wang, J and White, ES and Hwang, TS and Jia, Y and Bailey, ST},
title = {Detection of Macular Neovascularization in Eyes Presenting with Macular Edema using OCT Angiography and a Deep Learning Model.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {4},
pages = {378-385},
pmid = {39461425},
issn = {2468-6530},
support = {P30 EY010572/EY/NEI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; R01 EY024544/EY/NEI NIH HHS/United States ; R01 EY031394/EY/NEI NIH HHS/United States ; R01 EY035410/EY/NEI NIH HHS/United States ; T32 EY023211/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Edema/diagnosis/etiology/complications ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; *Deep Learning ; *Fluorescein Angiography/methods ; Prospective Studies ; Male ; Female ; Aged ; Fundus Oculi ; *Macula Lutea/pathology ; Middle Aged ; *Retinal Neovascularization/diagnosis ; Visual Acuity ; Aged, 80 and over ; Diabetic Retinopathy/complications/diagnosis ; Retinal Vein Occlusion/complications/diagnosis ; Algorithms ; },
abstract = {PURPOSE: To test the diagnostic performance of an artificial intelligence algorithm for detecting and segmenting macular neovascularization (MNV) with OCT and OCT angiography (OCTA) in eyes with macular edema from various diagnoses.<br><br>DESIGN: Prospective cross-sectional study.<br><br>PARTICIPANTS: Study participants with macular edema due to either treatment-na&#xef;ve exudative age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO).<br><br>METHODS: Study participants were imaged with macular 3&#xa0;&#xd7; 3-mm and 6&#xa0;&#xd7; 6-mm spectral-domain OCTA. Eyes with exudative AMD were required to have MNV in the central 3&#xa0;&#xd7; 3-mm area. A previously developed hybrid multitask convolutional neural network for MNV detection (aiMNV), and segmentation was applied to all images, regardless of image quality.<br><br>MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, and negative predictive value of detecting MNV and intersection over union (IoU) score and F1 score for segmentation.<br><br>RESULTS: Of 114 eyes from 112 study participants, 56 eyes had MNV due to exudative AMD and 58 eyes with macular edema due to either DME or RVO. The 3&#xa0;&#xd7; 3-mm OCTA scans with aiMNV detected MNV with 96.4% sensitivity, 98.3% specificity, 98.2% positive predictive value, and 96.6% negative predictive value. For segmentation, the average IoU score was 0.947, and the F1 score was 0.973. The 6&#xa0;&#xd7; 6-mm scans performed well; however, sensitivity for MNV detection was lower than 3&#xa0;&#xd7; 3-mm scans due to lower scan sampling density.<br><br>CONCLUSIONS: This novel aiMNV algorithm can accurately detect and segment MNV in eyes with exudative AMD from a control group of eyes that present with macular edema from either DME or RVO. Higher scan sampling density improved the aiMNV sensitivity for MNV detection.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39461364,
year = {2025},
author = {Nassrallah, EI and Denis, R and Nassrallah, G and Dias, AB and Ito, H and Mastromonaco, C and Saheb, N and Burnier, MN},
title = {Unintended placement of intraocular lens haptics in the sulcus and its association with posterior capsular opacification in pseudophakic post-mortem eyes.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {3},
pages = {129-134},
doi = {10.1016/j.jcjo.2024.09.010},
pmid = {39461364},
issn = {1715-3360},
mesh = {Humans ; Cross-Sectional Studies ; Female ; *Pseudophakia/complications/diagnosis ; Male ; *Lenses, Intraocular/adverse effects ; Aged ; *Capsule Opacification/etiology/diagnosis ; *Lens Implantation, Intraocular/adverse effects ; Aged, 80 and over ; Middle Aged ; *Lens Capsule, Crystalline/pathology ; Autopsy ; },
abstract = {OBJECTIVE: To assess the prevalence of unintended placement of intraocular lens (IOL) haptics in the sulcus and its association with posterior capsular opacification (PCO).<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: 428 post-mortem pseudophakic human eyes.<br><br>METHODS: Eyes were obtained from the Lions Gift of Sight and imaged in Miyake-Apple view (MAV). IOL haptic placement (bag-bag, bag-sulcus, sulcus-sulcus) was determined from the MAV images. IOL-capsular bag complexes were extracted and analyzed via Automated Detector Opacification Software to quantify PCO and Soemmering's Ring (SR). SR distribution was categorized as focal, diffuse, or none. Mean differences in PCO and SR between haptic groups were assessed via Welch's t-test. Odds ratios were used to compare the risk of SR distribution patterns between both haptic groups. Sex, clinical history (diabetes, smoking, hypertension, glaucoma, cancer, age-related macular degeneration [AMD], hypercholesterolemia, cardiovascular disease), and IOL model and specifications were collected.<br><br>RESULTS: 20 eyes (4.67%) had unintended sulcus placement of haptics. Mean PCO (p&#x202f;=&#x202f;0.0367) and SR (p&#x202f;=&#x202f;0.0414) were significantly higher in sulcus eyes. Sulcus eyes were significantly more at risk of focal SR distribution (OR 8.715; p < 0.0001) and significantly less at risk of diffuse SR distribution (OR 0.168; p&#x202f;=&#x202f;.0007). Sulcus eyes had significantly higher frequencies of glaucoma (p < 0.0001) and AMD (p&#x202f;=&#x202f;0.0023) on clinical history.<br><br>CONCLUSIONS: This study demonstrates that unintended sulcus placement of IOL haptics may be associated with an increased risk of PCO and SR formation. This study offers clinical signs of sulcus haptic placement that may prompt physicians to seek earlier appropriate intervention.},
}
@article {pmid39460687,
year = {2024},
author = {Ramirez, JA and Khurana, RN and Wang, JC},
title = {A novel case of endophthalmitis secondary to Paenibacillus yonginensis after intravitreal injection of aflibercept.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001623},
pmid = {39460687},
issn = {1937-1578},
abstract = {PURPOSE: To report a case of endophthalmitis after intravitreal injection due to Paenibacillus yonginensis.<br><br>METHODS: This is a retrospective case report.<br><br>RESULTS: An 87-year-old man with longstanding neovascular age-related macular degeneration (AMD) in his left eye presented with pain and loss of vision three days after intravitreal injection of aflibercept. Examination revealed a hypopyon and vitreous opacities. A diagnostic anterior chamber paracentesis and intravitreal injections of vancomycin and ceftazidime were performed. One month later, vitrectomy was performed for non-clearing vitreous opacities with a good final visual outcome. The causative bacterium, Paenibacillus yonginensis, was identified with polymerase chain reaction (PCR) sequencing from the aqueous specimen.<br><br>CONCLUSION: We encountered a rare presentation of endophthalmitis caused by Paenibacillus yonginensis. Paenibacillus species have been implicated in human infection in recent years. DNA sequencing can allow for the identification of uncommon bacteria.},
}
@article {pmid39459520,
year = {2024},
author = {Moraru, AD and Danielescu, C and Iorga, RE and Moraru, RL and Zemba, M and Branisteanu, DC},
title = {Review of Guideline Recommendations for Optimal Anti-VEGF Therapy in Age-Related Macular Degeneration.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
pmid = {39459520},
issn = {2075-1729},
abstract = {Neovascular age-related macular degeneration is a progressive, blinding macular disease that has become a burden both in healthcare systems and the global economy. The vascular endothelial growth factor (VEGF) is the main agent involved in the pathogenic process of the disease. The main goal of the age-related macular degeneration treatment is to maintain and improve visual acuity by injecting intravitreal anti-VEGF agents in either a reactive or proactive manner. Subretinal and intraretinal fluids are the main biomarkers that should be considered when managing the frequency of the therapy. This review discusses both functional and morphological treatment criteria according to current recommendations as opposed to real-life situations encountered during day-to-day clinical practice and highlights situations in which the benefits of continuing therapy are arguable in terms of improving patients' quality of life. Optimizing the treatment regimen represents an important aim of current clinical ophthalmological practice, as age-related macular degeneration patients usually have a long follow-up period.},
}
@article {pmid39459435,
year = {2024},
author = {Singh, M and Negi, R and Alka, and Vinayagam, R and Kang, SG and Shukla, P},
title = {Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {10},
pages = {},
pmid = {39459435},
issn = {1648-9144},
mesh = {Humans ; *Macular Degeneration/drug therapy/physiopathology ; *Drug Delivery Systems/methods ; Oxidative Stress/drug effects ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; },
abstract = {The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices.},
}
@article {pmid39458628,
year = {2024},
author = {Wu, KY and Dhaliwal, JK and Sasitharan, A and Kalevar, A},
title = {Cell Therapy for Retinal Degenerative Diseases: Progress and Prospects.},
journal = {Pharmaceutics},
volume = {16},
number = {10},
pages = {},
pmid = {39458628},
issn = {1999-4923},
abstract = {Background/Objectives: Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are leading causes of vision loss, with AMD affecting older populations and RP being a rarer, genetically inherited condition. Both diseases result in progressive retinal degeneration, for which current treatments remain inadequate in advanced stages. This review aims to provide an overview of the retina's anatomy and physiology, elucidate the pathophysiology of AMD and RP, and evaluate emerging cell-based therapies for these conditions. Methods: A comprehensive review of the literature was conducted, focusing on cell therapy approaches, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells. Preclinical and clinical studies were analyzed to assess therapeutic potential, with attention to mechanisms such as cell replacement, neuroprotection, and paracrine effects. Relevant challenges, including ethical concerns and clinical translation, were also explored. Results: Cell-based therapies demonstrate potential for restoring retinal function and slowing disease progression through mechanisms like neuroprotection and cell replacement. Preclinical trials show promising outcomes, but clinical studies face significant hurdles, including challenges in cell delivery and long-term efficacy. Combination therapies integrating gene editing and biomaterials offer potential future advancements. Conclusions: While cell-based therapies for AMD and RP have made significant progress, substantial barriers to clinical application remain. Further research is essential to overcome these obstacles, improve delivery methods, and ensure the safe and effective translation of these therapies into clinical practice.},
}
@article {pmid39458195,
year = {2024},
author = {Kominami, A and Tomita, S and Kato, A and Ono, K and Takeuchi, M and Imazeki, M and Terasaki, H and Yamamoto, Y and Jujo, T and Wakuta, M and Matsubara, H and Mitamura, Y and Kondo, M and Kimura, K and Takagi, H and Gomi, F and Sakamoto, T and Yasukawa, T and , },
title = {Factors Affecting Visual Acuity After Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration: A Multicenter Study in Japan.},
journal = {Journal of clinical medicine},
volume = {13},
number = {20},
pages = {},
pmid = {39458195},
issn = {2077-0383},
abstract = {Background/Objectives: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular age-related macular degeneration (nvAMD). While proactive and adequate treatment generally leads to better visual outcomes, various factors, including the disease type, ocular findings, lifestyle, and systemic status, affect the visual prognosis in clinical settings. This study aimed to identify the factors that affect the visual prognosis in patients with nvAMD treated with anti-VEGF therapy. Methods: We conducted a multicenter retrospective cohort study at eight tertiary referral centers in Japan, where we reviewed the medical records of patients newly diagnosed with nvAMD between January 2014 and December 2019. These patients had started treatment with either ranibizumab (0.5 mg) or aflibercept (2.0 mg) and were followed for at least 1 year. We evaluated the impact of the disease type, systemic factors, and initial fundus findings on the best-corrected visual acuity (BCVA) at 1 year. Results: This study included 182 patients (129 men, 53 women), with a mean age of 75.0 ± 8.6 years. The disease types were categorized as typical AMD (53%), polypoidal choroidal vasculopathy (PCV) (43%), and retinal angiomatous proliferation (RAP) (4%). Univariate analysis identified age, the baseline logarithm of the minimum angle of resolution BCVA, intraretinal fluid (IRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM). Multivariate analysis identified the following significant risk factors associated with vision worsening: age, smoking history, diabetes, and the presence of IRF and PED. Conclusions: The presence of IRF, PED, and SHRM at the start of treatment and a history of smoking and diabetes may be associated with a poor visual prognosis in patients with nvAMD.},
}
@article {pmid39456672,
year = {2024},
author = {Duncan, RS and Keightley, A and Lopez, AA and Hall, CW and Koulen, P},
title = {Proteomics Analysis on the Effects of Oxidative Stress and Antioxidants on Proteins Involved in Sterol Transport and Metabolism in Human Telomerase Transcriptase-Overexpressing-Retinal Pigment Epithelium Cells.},
journal = {International journal of molecular sciences},
volume = {25},
number = {20},
pages = {},
pmid = {39456672},
issn = {1422-0067},
support = {R01 EY030747/EY/NEI NIH HHS/United States ; 1R01EY030747-03A99/NH/NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Oxidative Stress/drug effects ; *Proteomics/methods ; *Telomerase/metabolism/genetics ; *Antioxidants/metabolism/pharmacology ; *Sterols/metabolism/pharmacology ; Biological Transport/drug effects ; Cell Line ; Tocopherols/pharmacology/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the most prevalent ocular disease in the elderly, resulting in blindness. Oxidative stress plays a role in retinal pigment epithelium (RPE) pathology observed in AMD. Tocopherols are potent antioxidants that prevent cellular oxidative damage and have been shown to upregulate the expression of cellular antioxidant proteins. Here, we determined whether oxidative stress and tocopherols, using either normal cellular conditions or conditions of sublethal cellular oxidative stress, alter the expression of proteins mediating sterol uptake, transport, and metabolism. Human telomerase transcriptase-overexpressing RPE cells (hTERT-RPE) were used to identify differential expression of proteins resulting from treatments. We utilized a proteomics strategy to identify protein expression changes in treated cells. After the identification and organization of data, we divided the identified proteins into groups related to biological function: cellular sterol uptake, sterol transport and sterol metabolism. Exposure of cells to conditions of oxidative stress and exposure to tocopherols led to similar protein expression changes within these three groups, suggesting that α-tocopherol (αT) and γ-tocopherol (γT) can regulate the expression of sterol uptake, transport and metabolic proteins in RPE cells. These data suggest that proteins involved in sterol transport and metabolism may be important for RPE adaptation to oxidative stress, and these proteins represent potential therapeutic targets.},
}
@article {pmid39456195,
year = {2024},
author = {Valero-Ochando, J and Cantó, A and López-Pedrajas, R and Almansa, I and Miranda, M},
title = {Role of Gonadal Steroid Hormones in the Eye: Therapeutic Implications.},
journal = {Biomolecules},
volume = {14},
number = {10},
pages = {},
pmid = {39456195},
issn = {2218-273X},
support = {"Ayudas para la Consolidaci&#xf3;n de Indicadores de Investigaci&#xf3;n UCH CEU 2023-2024", "Ayudas para grupos de investigaci&#xf3;n reconocidos en Registro de Grupos (GIR) UCH CEU 2023-2024", "Ayudas IDOC23-12 UCH CEU" and "Proyectos Puente y en Consolidaci&#xf3;n de la Fu//Fundaci&#xf3;n Universitaria San Pablo CEU/ ; },
mesh = {Humans ; *Gonadal Steroid Hormones/metabolism ; Animals ; Retina/metabolism ; Eye/metabolism ; Retinal Diseases/metabolism/drug therapy ; Glaucoma/metabolism/drug therapy ; },
abstract = {Gonadal steroid hormones are critical regulatory substances involved in various developmental and physiological processes from fetal development through adulthood. These hormones, derived from cholesterol, are synthesized primarily by the gonads, adrenal cortex, and placenta. The synthesis of these hormones involves a series of enzymatic steps starting in the mitochondria and includes enzymes such as cytochrome P450 and aromatase. Beyond their genomic actions, which involve altering gene transcription over hours, gonadal steroids also exhibit rapid, nongenomic effects through receptors located on the cell membrane. Additionally, recent research has highlighted the role of these hormones in the central nervous system (CNS). However, the interactions between gonadal steroid hormones and the retina have received limited attention, though it has been suggested that they may play a protective role in retinal diseases. This review explores the synthesis of gonadal hormones, their mechanisms of action, and their potential implications in various retinal and optic nerve diseases, such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), or retinitis pigmentosa (RP), discussing both protective and risk factors associated with hormone levels and their therapeutic potential.},
}
@article {pmid39455036,
year = {2025},
author = {Kaufmann, GT and Boucher, N and Sharma, C and Aggarwal, N and Starr, MR},
title = {Submacular Hemorrhage Rates Following Anti-Vascular Endothelial Growth Factor Injections for Exudative Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {270},
number = {},
pages = {172-182},
doi = {10.1016/j.ajo.2024.10.017},
pmid = {39455036},
issn = {1879-1891},
mesh = {Humans ; Retrospective Studies ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Female ; Visual Acuity ; *Retinal Hemorrhage/epidemiology/diagnosis/chemically induced ; Aged ; Bevacizumab/adverse effects/administration &amp; dosage ; Ranibizumab/adverse effects/administration &amp; dosage ; Recombinant Fusion Proteins/adverse effects/administration &amp; dosage ; Aged, 80 and over ; Receptors, Vascular Endothelial Growth Factor ; Follow-Up Studies ; Antibodies, Monoclonal, Humanized ; },
abstract = {PURPOSE: To examine rates of submacular hemorrhage in patients undergoing anti-vascular endothelial growth factor (VEGF) injections, comparing rates between specific anti-VEGF agents.<br><br>DESIGN: Retrospective clinical cohort study.<br><br>METHODS: All patients in the database from January 2015 to November 2023 with a diagnosis of neovascular age-related macular degeneration and accompanying submacular hemorrhage (SMH). SMH prevalence and associated anti-VEGF injection type were analyzed in 140,915 eyes (of which 9107 had SMH) in a nationwide aggregated electronic health care database using chi-square test of proportion. Visual acuity (VA) data was assessed using 2-sample independent t-tests. The primary outcome was rate of SMH per injection type. Secondary datapoints examined were time between SMH diagnosis and last anti-VEGF injection, number of injections before SMH, treatment interval at time of SMH, VA before and at 12 months after SMH, eyes undergoing pars plana vitrectomy (PPV) within 30 days of SMH, and VA before PPV and at 12 months after PPV.<br><br>RESULTS: The last injection type in eyes with SMH was bevacizumab in 3430 (37.8%) eyes, brolucizumab-dbll in 46 (0.51%) eyes, aflibercept in 3221 (35.4%) eyes. Ranibizumab in 2246 (24.7%) eyes, and faricimab-svoa in 155 (1.7%) eyes. Rates of SMH were significantly higher (P &#x2264; .001) for last injection with bevacizumab compared to every other injection type. Rates of SMH were significantly lower (P = .0004) for last injection with faricimab-svoa or ranibizumab injections each had significantly shorter (mean and standard deviation 48.9 (27.9), P < .02; mean and standard deviation 59.6 (38.2), P = .003, respectively) mean time between SMH diagnosis and last injection than did patients undergoing any other injection. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type among all patients. The number of patients who underwent PPV were 52 (1.51%) for bevacizumab, 4 (8.7%) for brolucizumab-dbll, 58 (1.8%) for aflibercept, 41 (1.8%) for ranibizumab, and 3 (1.9%) for faricimab-svoa. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type in patients undergoing PPV.<br><br>CONCLUSIONS: Faricimab may be more protective than other anti-VEGF injections against SMH in patients with neovascular age-related macular degeneration.},
}
@article {pmid39454055,
year = {2025},
author = {Blazes, M and Ngadisastra, C and Li, PR and Lee, CS and Lee, JS and See, LC and Lin, KK},
title = {INCIDENCE AND PROGRESSION OF AGE-RELATED MACULAR DEGENERATION AMONG PATIENTS WITH AND WITHOUT OBSTRUCTIVE SLEEP APNEA: A National Cohort Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {2},
pages = {198-206},
pmid = {39454055},
issn = {1539-2864},
support = {R01 AG060942/AG/NIA NIH HHS/United States ; CFRPG1N0011//Chang Gung Memorial Hospital/ ; R01AG060942/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Sleep Apnea, Obstructive/complications/epidemiology ; Female ; Male ; Disease Progression ; Incidence ; Aged ; Taiwan/epidemiology ; Middle Aged ; Risk Factors ; Retrospective Studies ; *Macular Degeneration/epidemiology ; Follow-Up Studies ; Aged, 80 and over ; },
abstract = {PURPOSE: Obstructive sleep apnea (OSA) may increase the risk of age-related macular degeneration (AMD) due to repetitive oxygen deprivation or other mechanisms, though whether OSA increases the risk of AMD progression is unknown. The authors analyzed associations between OSA and AMD risk in the Taiwanese population.<br><br>METHODS: The authors identified patients diagnosed with OSA between 2000 and 2018 in the Taiwan National Health Insurance Research Database and used 1:1 propensity score matching on demographics and comorbidities to create a non-OSA cohort. The authors used Cox proportional hazard modeling to investigate the risk of AMD and the risk of progression from nonexudative to exudative AMD in OSA versus non-OSA patients.<br><br>RESULTS: A total of 66,869 OSA patients were matched with 66,869 non-OSA patients. The hazard ratio of AMD in the OSA cohort was 1.36 (95% confidence interval, 1.29-1.43, P < 0.0001). The hazard ratio for progression from nonexudative to exudative AMD for the OSA cohort was 0.94 (95% confidence interval, 0.77-1.14, P = 0.5073).<br><br>CONCLUSION: Obstructive sleep apnea is associated with a higher risk of developing AMD. However, no increased risk of AMD progression is observed among people with OSA and existing nonexudative AMD.},
}
@article {pmid39453673,
year = {2024},
author = {Leclercq, B and Mejlachowicz, D and Zhu, L and Jonet, L and Mehanna, C and Berdugo, M and Irinopoulou, T and Jaisser, F and Zhao, M and Behar-Cohen, F},
title = {Differential Effect of Aldosterone or Mineralocorticoid Receptor Overexpression on Retinal Inflammation.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {12},
pages = {39},
pmid = {39453673},
issn = {1552-5783},
mesh = {Animals ; *Aldosterone ; *Receptors, Mineralocorticoid/metabolism/genetics ; Rats ; Rats, Transgenic ; Retinal Pigment Epithelium/metabolism/pathology ; Retinitis/metabolism/genetics ; Disease Models, Animal ; Male ; Gene Expression Regulation ; Retina/metabolism ; Humans ; Intravitreal Injections ; Choroid/metabolism/pathology ; },
abstract = {PURPOSE: Overactivation of the mineralocorticoid receptor (MR) pathway is proinflammatory and contributes to the pathogenesis of diabetic retinopathy and of age-related macular degeneration. Excess of aldosterone, the specific MR ligand, is known to stimulate the production of proinflammatory cytokines and chemokines in extrarenal tissues and cells. In the RPE/choroid complex, aldosterone upregulated genes encoding proteins of the inflammatory response and downregulated genes encoding proteins involved in synaptic activity and neurotransmitters. Yet, cortisol, which is the main MR ligand in the eye, is a potent anti-inflammatory endogenous glucocorticoid. The aim of the present work was to better understand the role of MR activation in retinal inflammation either by acute injection of aldosterone or overexpression of the receptor.<br><br>METHODS: We first analyzed the retinal transcriptomic regulation induced by acute intraocular injection of aldosterone in the rat. Then, we used a transgenic rat overexpressing human MR (hMR) to also conduct retinal transcriptomic analysis as well as histological evaluation of the retina, retinal pigment epithelium and choroid.<br><br>RESULTS: Our results show that acute intravitreal injection of aldosterone is highly proinflammatory, upregulating pathways related to microglial activation, oxidative stress, cell death, and downregulating pathways related to glial/neuronal cells activity and proper neurotransmission. On the other hand, hMR overexpression mediates a low-grade inflammation in the retina, associated with notable choroidal inflammation and choroidal neuropathy.<br><br>CONCLUSIONS: Consequences of hMR overexpression or aldosterone-injection on retinal transcriptome reveal very distinct pathological mechanisms, with only a few common genes regulated, most of them not being regulated in the same way. Although aldosterone is highly proinflammatory in the retina, MR overactivation in its physiologic milieu mediates a low-grade inflammation in the neural retina.},
}
@article {pmid39452548,
year = {2024},
author = {Kuo, YW and Lee, CY and Hsieh, YT and Yang, CM and Ho, TC and Lai, TT and Yang, CH},
title = {Impact of Anti-Vascular Endothelial Growth Factor Treatment on Neovascular Age-Related Macular Degeneration with and without Retinal Pigment Epithelial Detachment: A Real-World Study.},
journal = {Journal of personalized medicine},
volume = {14},
number = {10},
pages = {},
pmid = {39452548},
issn = {2075-4426},
abstract = {BACKGROUND/OBJECTIVES: This study evaluates the impact of anti-vascular endothelial growth factor (anti-VEGF) treatment on neovascular age-related macular degeneration (nAMD) with and without pigment epithelial detachment (PED) over a one-year period.<br><br>METHODS: Conducted at a tertiary referral center in Taiwan, this retrospective analysis included 88 eyes treated with intravitreal aflibercept injections. Patients were categorized into four groups based on the presence or absence of PED at baseline and 12 months post-treatment.<br><br>RESULTS: Significant reductions in central macular thickness (CMT) and PED height were observed, although no statistical difference was found in best-corrected visual acuity (BCVA). The presence or type of PED did not negatively impact visual outcomes. Among nAMD patients with persistent PED throughout the first year of anti-VEGF treatment, linear regression analysis showed that mixed-type PED revealed poor final BCVA compared to those with serous PED. The analysis also identified older age and poorer initial BCVA as predictors of less favorable visual outcomes.<br><br>CONCLUSIONS: This study highlights the effectiveness of anti-VEGF therapy in real-world settings and offers insights into factors influencing visual outcomes for nAMD patients with PED.},
}
@article {pmid39451407,
year = {2024},
author = {Karn, PK and Abdulla, WH},
title = {Precision Segmentation of Subretinal Fluids in OCT Using Multiscale Attention-Based U-Net Architecture.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {10},
pages = {},
pmid = {39451407},
issn = {2306-5354},
abstract = {This paper presents a deep-learning architecture for segmenting retinal fluids in patients with Diabetic Macular Oedema (DME) and Age-related Macular Degeneration (AMD). Accurate segmentation of multiple fluid types is critical for diagnosis and treatment planning, but existing techniques often struggle with precision. We propose an encoder-decoder network inspired by U-Net, processing enhanced OCT images and their edge maps. The encoder incorporates Residual and Inception modules with an autoencoder-based multiscale attention mechanism to extract detailed features. Our method shows superior performance across several datasets. On the RETOUCH dataset, the network achieved F1 Scores of 0.82 for intraretinal fluid (IRF), 0.93 for subretinal fluid (SRF), and 0.94 for pigment epithelial detachment (PED). The model also performed well on the OPTIMA and DUKE datasets, demonstrating high precision, recall, and F1 Scores. This architecture significantly enhances segmentation accuracy and edge precision, offering a valuable tool for diagnosing and managing retinal diseases. Its integration of dual-input processing, multiscale attention, and advanced encoder modules highlights its potential to improve clinical outcomes and advance retinal disease treatment.},
}
@article {pmid39451126,
year = {2024},
author = {Hwang, JS and Song, HB and Lee, G and Jeong, S and Ma, DJ},
title = {Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stem Cells Alleviate Apoptosis and Oxidative Stress of Retinal Pigment Epithelial Cells Through Activation of Nrf2 Signaling Pathway.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {40},
number = {10},
pages = {688-701},
doi = {10.1089/jop.2024.0064},
pmid = {39451126},
issn = {1557-7732},
mesh = {Animals ; *Extracellular Vesicles/metabolism ; *NF-E2-Related Factor 2/metabolism ; *Apoptosis/drug effects ; *Oxidative Stress/drug effects ; Rats ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Mesenchymal Stem Cells/metabolism ; *Signal Transduction/drug effects ; Humans ; Retinal Degeneration/metabolism/pathology ; Hydrogen Peroxide/toxicity/pharmacology ; Adipose Tissue/cytology ; Male ; },
abstract = {Purpose: To examine the potential protective effects of adipose-derived mesenchymal stem cell-derived extracellular vesicles (ASC-EVs) on ARPE-19 cells exposed to hydrogen peroxide (H2O2) stress and to evaluate their ability to delay retinal degeneration in Royal College of Surgeons (RCS) rats. Methods: ARPE-19 cells were pre-treated with ASC-EVs for 24 h, followed by exposure to 200 μM H2O2 for an additional 24 h. RCS rats received an intravitreal injection of phosphate-buffered saline in one eye and ASC-EVs in the other eye. Results: ASC-EV pretreatment significantly protected against H2O2 in the Cell Counting Kit-8 assay and was also effective in the lactate dehydrogenase-release assay. It notably reduced early apoptosis (Annexin V-fluorescein isothiocyanate/propidium iodide assay) and late apoptosis (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling assay), while significantly decreasing intracellular reactive oxygen species, glutathione levels, and superoxide dismutase activity. NFE2L2, HMOX1, and NQO1 mRNA levels, along with Nrf2, HO-1, and NQO1 protein levels, were significantly elevated with ASC-EV pretreatment. Compared with ARPE-19-derived EVs, 11 miRNAs were upregulated and 34 were downregulated in ASC-EVs. In RCS rats, intravitreal injections of ASC-EVs led to significant preservation of the outer nuclear layer and photoreceptor segments, along with increased nuclear Nrf2 expression and elevated HO-1 and NQO1 levels in the inner retina. Eyes that received intravitreal injections of ASC-EVs demonstrated significantly preserved electroretinography a- and b-wave amplitudes at 1 week post-injection, though this effect faded by 2 weeks. Conclusions: ASC-EVs mitigated apoptosis and oxidative stress in ARPE-19 cells subjected to H2O2 exposure and temporarily slowed retinal degeneration in RCS rats via Nrf2 pathway activation by miRNAs.},
}
@article {pmid39450824,
year = {2024},
author = {Dugiełło, B and Wylęgała, A and Kijonka, M and Prus-Ludwig, A and Górska, G and Wylęgała, E and Orzechowska-Wylęgała, B},
title = {Vascular changes in optical coherence tomography angiography unveiling the depths of dry age-related macular degeneration: a review.},
journal = {Expert review of medical devices},
volume = {21},
number = {11},
pages = {1015-1029},
doi = {10.1080/17434440.2024.2419961},
pmid = {39450824},
issn = {1745-2422},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging ; Angiography/methods ; Retinal Vessels/diagnostic imaging ; },
abstract = {INTRODUCTION: Recent advancements in imaging techniques, particularly optical coherence tomography angiography (OCTA), have transformed our understanding of retinal microvascular changes in various ocular diseases, including dry age-related macular degeneration (AMD). Our literature review summarizes key findings on retinal vascular alterations in dry AMD as observed with OCTA, highlighting their implications for disease progression and management.<br><br>AREAS COVERED: Studies reveal significant changes in dry AMD patients, affecting the superficial and deep capillary plexuses as well as the choroid. These alterations include decreased vascular and flow density, variations in the foveal avascular zone, reduced choriocapillaris perfusion, and alterations in choroidal vascularity and thickness. Such changes reflect the complex vascular pathology of dry AMD and serve as potential biomarkers for monitoring disease progression. Variability in study results underscores the importance of considering AMD stage, sample size, follow-up duration, imaging protocols, and standardization.<br><br>EXPERT OPINION: OCTA in dry AMD is primarily research-focused due to technical and methodological challenges. Its adoption in clinical practice requires standardized protocols and improved software. With future advancements and a better understanding of disease pathology, OCTA could become a routine part of dry AMD management, especially as new therapies emerge that utilize OCTA for assessing dry AMD progression.},
}
@article {pmid39450444,
year = {2025},
author = {Scheffer, M and Menting, J and Rausch-Koster, P and van Nispen, R and van Dulmen, S},
title = {Looking beyond the eyes of the patient: The importance of effective communication in the treatment of age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {103},
number = {2},
pages = {205-214},
pmid = {39450444},
issn = {1755-3768},
support = {9431.4001//Stichting InZicht/ZonMw/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Communication ; *Physician-Patient Relations ; Surveys and Questionnaires ; *Macular Degeneration/therapy/psychology ; Aged, 80 and over ; Middle Aged ; Patient Satisfaction ; *Quality of Life ; Netherlands ; Wet Macular Degeneration/therapy/psychology ; },
abstract = {PURPOSE: Patients with exudative and nonexudative age-related macular degeneration (AMD) can experience physical, mental, social, administrative or financial burden that are associated with the treatment of this progressive chronic disease. The role of healthcare providers in supporting patients who experience high treatment burden can be important, especially when it comes to effective communication. Despite previous research underlining the need to improve patient-provider communication in AMD care, patient experiences with communication, and how these are related to perceived treatment burden, remain underexplored.<br><br>METHODS: A survey was distributed among Dutch patients with AMD, which contained questions on several aspects of communication with the patient's ophthalmologist, such as the Quality Of communication Through the patients' Eyes (QUOTE-COMM, including task-, affect- and therapy-oriented communication) questionnaire. Patients were primarily enlisted through a patient association.<br><br>RESULTS: A total of 162 patients completed the questionnaire, of which 133 provided fully completed responses. While patients reported positive experiences with affect-oriented communication of their ophthalmologist, they rated task- and therapy-oriented communication as below their expectations. Most patients wished to receive (additional) information on AMD-related costs (71%), future perspectives (71%) and coping with negative emotions pertaining to the disease (68%). Both lower experience scores on task- and affect-oriented communication and lower self-efficacy were associated with higher administrative burden and mental burden among patients.<br><br>CONCLUSION: Our study shows that current communication, information provision and decision-making do not fully meet patients' needs and preferences. Enhancing patient-provider communication seems important, as effective dialogue is likely to diminish patients' perceived treatment burden.},
}
@article {pmid39450123,
year = {2024},
author = {Wan, Z and Wu, Y and Shen, T and Hu, C and Lin, R and Ren, C and Yu, D and Li, T and Zhu, M and Cai, W and Yu, J},
title = {Evaluation of inflammatory hyperreflective foci and plasma EPA as diagnostic and predictive markers for age-related macular degeneration.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1401101},
pmid = {39450123},
issn = {1662-4548},
abstract = {OBJECTIVES: To detect the plasma polyunsaturated fatty acids (PUFAs) concentrations in age-related macular degeneration (AMD) patients and healthy controls. Additionally, advanced studies were conducted to investigate the relationship between PUFAs concentrations and ophthalmological characteristics, including hyperreflective foci (HRF), visual acuity, and anti-vascular endothelial growth factor (anti-VEGF) response in patients with AMD.<br><br>METHODS: This prospective, single-site study recruited a total of 315 participants, consisting of 105 individuals with dry AMD (early-stage AMD group), 105 individuals with neovascular AMD (late-stage AMD group), and 105 elderly individuals without any fundus diseases (healthy controls). The levels of omega-3 and omega-6 PUFAs in plasma were detected using gas chromatography. Retinal thickness, choroidal thickness, and macular volume were quantified using optical coherence tomography angiography (OCTA) scan with a 6 &#xd7; 6 mm macular area, and the amounts of HRF were analyzed with OCTA scanning data.<br><br>RESULTS: Compared to the control group, AMD patients exhibited significantly lower plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha linolenic acid. HRF were observed in various retinal layers of AMD patients, particularly those with late-stage AMD. The correlation coefficient matrix and multiple linear regression models demonstrated that HRF played a crucial role in best corrected visual acuity for both early (p < 0.001) and late-stage AMD patients (p = 0.006), while EPA had an inverse effect on the logarithm of the minimum angle of resolution (logMAR) value in patients with early-stage AMD (p < 0.001). As compared to patients with good responses to anti-VEGF therapy, those with poor responses had significantly lower baseline logMAR (p < 0.001), central retina thickness (p = 0.002), macular volume (p = 0.027), HRF (p = 0.024), and plasma EPA (p < 0.001). This study used a ROC curve analysis to identify the combination of HRF and EPA as a potential biomarker for predicting the response to anti-VEGF treatment in late-stage AMD patients, with an area under the curve (AUC) value of 0.775.<br><br>CONCLUSIONS: Reduced plasma EPA was detected in AMD cases and the lower EPA concentration was related to poorer visual acuity. Additionally, the quantity of HRF combined with concentration of plasma EPA may serve as the prognostic indicator for predicting the effect of anti-VEGF treatment in late-stage AMD patients.},
}
@article {pmid39449758,
year = {2024},
author = {Pannek, S and Dehghani, S and Sommersperger, M and Zhang, P and Gehlbach, P and Nasseri, MA and Iordachita, I and Navab, N},
title = {Exploring the Needle Tip Interaction Force with Retinal Tissue Deformation in Vitreoretinal Surgery.},
journal = {IEEE International Conference on Robotics and Automation : ICRA : [proceedings]. IEEE International Conference on Robotics and Automation},
volume = {2024},
number = {},
pages = {16999-17005},
pmid = {39449758},
issn = {2152-4092},
support = {R01 EB023943/EB/NIBIB NIH HHS/United States ; R01 EB025883/EB/NIBIB NIH HHS/United States ; },
abstract = {Recent advancements in age-related macular degeneration treatments necessitate precision delivery into the subretinal space, emphasizing minimally invasive procedures targeting the retinal pigment epithelium (RPE)-Bruch's membrane complex without causing trauma. Even for skilled surgeons, the inherent hand tremors during manual surgery can jeopardize the safety of these critical interventions. This has fostered the evolution of robotic systems designed to prevent such tremors. These robots are enhanced by FBG sensors, which sense the small force interactions between the surgical instruments and retinal tissue. To enable the community to design algorithms taking advantage of such force feedback data, this paper focuses on the need to provide a specialized dataset, integrating optical coherence tomography (OCT) imaging together with the aforementioned force data. We introduce a unique dataset, integrating force sensing data synchronized with OCT B-scan images, derived from a sophisticated setup involving robotic assistance and OCT integrated microscopes. Furthermore, we present a neural network model for image-based force estimation to demonstrate the dataset's applicability.},
}
@article {pmid39449532,
year = {2024},
author = {Batıoğlu, F and Yanık, &#xd6; and Ellialtıoğlu, PA and Demirel, S and Şahlı, E and Özmert, E},
title = {A comparative study of choroidal structural features in eyes with central macular atrophy related to Stargardt disease and non-exudative age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 5},
pages = {S887-S892},
pmid = {39449532},
issn = {1998-3689},
mesh = {Humans ; *Stargardt Disease/diagnosis ; Male ; Retrospective Studies ; Female ; *Tomography, Optical Coherence/methods ; Middle Aged ; *Choroid/pathology/diagnostic imaging ; *Fluorescein Angiography/methods ; Aged ; *Visual Acuity ; *Fundus Oculi ; Macular Degeneration/diagnosis/congenital ; Macula Lutea/pathology ; Follow-Up Studies ; },
abstract = {PURPOSE: To compare choroidal structural features in eyes with central macular atrophy related to Stargardt disease (STGD) and non-exudative age-related macular degeneration (AMD).<br><br>METHODS: Twenty-five eyes of 25 Stargardt cases and 25 eyes of 25 non-exudative AMD cases were included in this retrospective study. Region Finder software was used to measure atrophic areas on blue-light fundus autofluorescence images centered on the macula. The total choroidal area (TCA), luminal area (LA), and stromal area (SA) were calculated using the ImageJ program and Niblack autolocal thresholding method. The choroidal vascularity index (CVI) was assessed.<br><br>RESULTS: The mean age was 59.4 &#xb1; 10.9 years in the STGD group and 68.1 &#xb1; 7.6 years in the non-exudative AMD group (P = 0.002). The mean macular atrophic area was 16.06 &#xb1; 10.61 mm2 in STGD and 11.73 &#xb1; 7.65 mm2 in non-exudative AMD (P = 0.171). The STGD group had significantly higher mean subfoveal choroidal thickness (184.0 &#xb1; 62.6 vs. 131.8 &#xb1; 62.4 &#xb5;m), TCA (0.553 &#xb1; 0.201 vs. 0.406 &#xb1; 0.189 mm2), LA (0.344 &#xb1; 0.150 vs. 0.253 &#xb1; 0.124 mm2), and SA values (0.208 &#xb1; 0.062 vs. 0.153 &#xb1; 0.069 mm2) compared to the non-exudative AMD group (P = 0.004, P = 0.011, P = 0.023, and P = 0.004, respectively). However, CVI values did not differ significantly between the two groups (60.58 &#xb1; 7.4 vs. 61.93 &#xb1; 5.8%, P = 0.432). According to the results of the ANCOVA test, differences in mean SFCT, TCA, and SA persisted when the data were readjusted for age (P = 0.018, P = 0.035, and P = 0.017, respectively).<br><br>CONCLUSION: In non-exudative AMD with geographic atrophy, the reductions in the choroidal compartments are more pronounced than those in STGD. However, similar CVI values may suggest that controversy still exists regarding the role of choroidal compartmental changes in the development of atrophy.},
}
@article {pmid39449328,
year = {2024},
author = {Zong, Y and Miyagaki, M and Yang, M and Zhang, J and Zou, Y and Ohno-Matsui, K and Kamoi, K},
title = {Ophthalmic Use of Targeted Biologics in the Management of Intraocular Diseases: Current and Emerging Therapies.},
journal = {Antibodies (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
pmid = {39449328},
issn = {2073-4468},
support = {JP 20K09824//JSPS KAKENHI/ ; 22FC0201//Ministry of Health, Labor, and Welfare of Japan/ ; 23fk0108671h0001, 23fk0108672h0001//Japan Agency for Medical Research and Development, AMED/ ; FY2023//Takeda Science Foundation/ ; },
abstract = {BACKGROUND: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions.<br><br>METHODS: A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed.<br><br>RESULTS: Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-&#x3b1;) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios.<br><br>CONCLUSIONS: Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions.},
}
@article {pmid39447871,
year = {2025},
author = {Sheth, VS and Holekamp, NM and Khanani, AM and Rachitskaya, A and Blotner, S and Gune, S and Heinrich, D and Maass, KF and Chakravarthy, U},
title = {Retinal Fluid and Thickness Fluctuations in Archway Trial for Port Delivery System with Ranibizumab versus Monthly Ranibizumab Injections.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {4},
pages = {330-342},
doi = {10.1016/j.oret.2024.10.015},
pmid = {39447871},
issn = {2468-6530},
mesh = {Humans ; *Ranibizumab/administration &amp; dosage ; Intravitreal Injections ; Male ; Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Female ; *Tomography, Optical Coherence/methods ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Subretinal Fluid/diagnostic imaging ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Fluorescein Angiography/methods ; *Retina/pathology ; *Drug Delivery Systems ; Aged, 80 and over ; Treatment Outcome ; },
abstract = {PURPOSE: To determine proportion of eyes with neovascular age-related macular degeneration (nAMD) with retinal fluid and central subfield thickness (CST) fluctuations and evaluate their impact on best-corrected visual acuity (BCVA) in eyes treated with the Port Delivery System with ranibizumab (PDS) versus monthly intravitreal ranibizumab injections.<br><br>DESIGN: Post hoc analyses of phase 3 Archway trial (NCT03677934).<br><br>PARTICIPANTS: Adults with nAMD responsive to anti-VEGF therapy.<br><br>INTERVENTION: Four hundred eighteen patients randomized 3:2 to the PDS (100 mg/mL) with refill-exchanges every 24 weeks (Q24W) or monthly intravitreal ranibizumab (0.5 mg) for 96 weeks.<br><br>OUTCOMES: Proportion of eyes in each treatment arm with subretinal and/or intraretinal fluid (SRF/IRF) overall and in central 1 mm; BCVA changes from baseline by treatment arm and fluid presence/location; proportion of eyes with CST fluctuations from baseline to week 48, week 48 to 96, and baseline to week 96; effects of CST fluctuations on BCVA.<br><br>RESULTS: Four hundred fifteen eyes were assessed. In the PDS versus monthly ranibizumab arm, proportion of eyes with SRF/IRF, central SRF, and central IRF were 47.6% versus 50.9%, 29.0% versus 19.2%, and 11.7% versus 12.6% at baseline, and 57.8% versus 56.1%, 21.6% versus 14.8%, and 7.0% versus 8.4% at week 96, respectively. BCVA changes from baseline to week 96 were&#xa0;-1.1 letters with the PDS versus&#xa0;-1.4 with monthly ranibizumab in eyes with SRF/IRF, and&#xa0;-1.9 versus&#xa0;-1.8 in eyes with central SRF. In eyes with central IRF, BCVA changes from baseline to week 96 were&#xa0;-2.1 with the PDS versus&#xa0;-6.9 with monthly ranibizumab, respectively (mean BCVA at 96 weeks 68.9 [20/40] vs. 64.6 [20/50]). CST fluctuations occurred in 32.1% and 29.7% of PDS versus monthly ranibizumab eyes; corresponding BCVA changes from baseline to week 96 were&#xa0;-2.5 versus&#xa0;-2.6 (mean BCVA at 96 weeks 72.7 [20/35] vs. 71.5 [20/38]).<br><br>CONCLUSIONS: Port Delivery System with ranibizumab Q24W maintained BCVA to 96 weeks regardless of SRF/IRF, central SRF, central IRF, or CST fluctuations, comparable with monthly ranibizumab, thus supporting the use of the PDS in stabilizing retinal anatomy without the need for monthly treatment in patients with nAMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39446815,
year = {2025},
author = {Yan, A and Hasan, N and Chhablani, J},
title = {Dry and neovascular "wet" age-related macular degeneration: Upcoming therapies.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {Suppl 1},
pages = {S55-S65},
pmid = {39446815},
issn = {1998-3689},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Genetic Therapy/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Geographic Atrophy/drug therapy/diagnosis/therapy ; Intravitreal Injections ; },
abstract = {The age-related macular degeneration (AMD) field is witnessing promising advancements in therapeutic options. Breakthrough drugs such as pegcetacoplan and avacincaptad have been FDA-approved for dry AMD, marking a significant development as there were no treatment options until August 2023. While several antivascular endothelial growth factor (VEGF) inhibitors have been approved for wet AMD, challenges persist with the need for frequent dosing. New treatments such as gene therapy, cell therapy, WNT pathway agonists, complement inhibitors, and anti-VEGF combination drugs are under development to address these issues. These developments are exciting and hold promise for transforming the field of medicine, offering hope for improved outcomes and enhanced patient care in managing AMD.},
}
@article {pmid39446346,
year = {2024},
author = {Alsoudi, AF and Wai, KM and Koo, E and Mruthyunjaya, P and Rahimy, E},
title = {Curcuma-Based Nutritional Supplements and Risk of Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {142},
number = {12},
pages = {1114-1121},
pmid = {39446346},
issn = {2168-6173},
mesh = {Humans ; Female ; Male ; Retrospective Studies ; *Dietary Supplements ; Aged ; *Curcuma ; Risk Factors ; Middle Aged ; Macular Degeneration/drug therapy ; Aged, 80 and over ; Wet Macular Degeneration/drug therapy/diagnosis ; Disease Progression ; Geographic Atrophy ; },
abstract = {IMPORTANCE: Curcuma-based nutritional supplements (CBNS) are natural anti-inflammatory and antioxidant agents that may confer benefits against age-related macular degeneration (AMD).<br><br>OBJECTIVE: To examine the association between the use of CBNS and the risk of development or progression of AMD.<br><br>This was a retrospective cohort study with data collection in June of 2024. Data were gathered from the aggregated electronic health records research network, TriNetX (Cambridge, Massachusetts). Patients without AMD were included in the study before propensity score matching (PSM); these included those taking and not taking CBNS. Patients with no history of AMD were stratified by instances of CBNS prescription records. Patients with a history of early nonexudative AMD stratified by instances of CBNS prescription records were also identified. PSM was performed to control for baseline demographics and medical comorbidities.<br><br>EXPOSURES: Patients were stratified by whether or not they were taking CBNS using RxNorm (National Library of Medicine) codes.<br><br>MAIN OUTCOME MEASURES: Relative risk (RR) of developing nonexudative AMD, exudative AMD, advanced nonexudative AMD or geographic atrophy (GA), blindness, or requiring intravitreal anti-vascular endothelial growth factor (VEGF) therapy.<br><br>RESULTS: A total of 66&#x202f;804 patients (mean [SD] age, 64.9 [10.1] years; 44&#x202f;124 female [66.1%]) taking CBNS and 1&#x202f;809&#x202f;440 patients (mean [SD] age, 67.0 [9.5] years; 999&#x202f;534 female [55.2%]) not taking CBNS were included in this study. Among patients without a history of AMD aged 50 years or older, CBNS use was associated with lower rates of developing nonexudative AMD (RR, 0.23; 95% CI, 0.21-0.26; P&#x2009;<&#x2009;.001), advanced nonexudative AMD or GA (RR, 0.11; 95% CI, 0.07-0.17; P&#x2009;<&#x2009;.001), exudative AMD (RR, 0.28; 95% CI, 0.24-0.32; P&#x2009;<&#x2009;.001), blindness (RR, 0.46; 95% CI, 0.36-0.59; P&#x2009;<&#x2009;.001), or requiring intravitreal anti-VEGF therapy (RR, 0.15; 95% CI, 0.13-0.17; P&#x2009;<&#x2009;.001) when compared with matched patients not taking CBNS. Results were consistent among subsets of patients 60 and 70 years or older, respectively. Among patients with early nonexudative AMD, subsequent instances of CBNS prescription records were associated with lower rates of developing advanced nonexudative AMD or GA (RR, 0.58; 95% CI, 0.41-0.81; P&#x2009;<&#x2009;.001) when compared with matched patients with early nonexudative AMD without a CBNS prescription record.<br><br>CONCLUSION AND RELEVANCE: Results of this cohort study suggest that a reduced risk of developing AMD or progression to later stages of AMD was associated with subsequent use of CBNS. Further investigation to validate these findings, safety, and potential pharmacoprotective mechanisms of CBNS in AMD are suggested.},
}
@article {pmid39446331,
year = {2024},
author = {Almidani, L and Ramulu, PY},
title = {Dementia Drugs and Age-Related Macular Degeneration.},
journal = {JAMA network open},
volume = {7},
number = {10},
pages = {e2441172},
doi = {10.1001/jamanetworkopen.2024.41172},
pmid = {39446331},
issn = {2574-3805},
}
@article {pmid39446320,
year = {2024},
author = {Wang, J and Antza, C and Lee, WH and Coker, J and Keane, PA and Denniston, AK and Nirantharakumar, K and Adderley, NJ},
title = {Pharmacologic Treatments for Dementia and the Risk of Developing Age-Related Macular Degeneration.},
journal = {JAMA network open},
volume = {7},
number = {10},
pages = {e2441166},
pmid = {39446320},
issn = {2574-3805},
support = {MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Female ; Male ; Aged ; *Memantine/therapeutic use ; *Macular Degeneration/drug therapy ; *Donepezil/therapeutic use ; *Dementia/drug therapy/epidemiology ; *Galantamine/therapeutic use ; Aged, 80 and over ; Cohort Studies ; Middle Aged ; Rivastigmine/therapeutic use ; Risk Factors ; Nootropic Agents/therapeutic use ; },
abstract = {IMPORTANCE: Age-related macular degeneration (AMD) is the leading cause of blindness among people aged 50 years or older worldwide. There is a need for new strategies for the prevention and treatment of AMD. There is some limited evidence to suggest the possibility of a protective association of dementia medications with the development of some types of AMD, but the evidence is weak.<br><br>OBJECTIVE: To investigate whether the dementia medications memantine and donepezil are associated with the risk of developing AMD.<br><br>Three population-based cohort studies were performed using data from the Clinical Practice Research Datalink GOLD and Aurum databases from May 15, 2002, to June 21, 2022. Participants included individuals with dementia (vascular dementia, nonvascular dementia, or Alzheimer disease) aged 40 years or older. Statistical analysis was carried out between February and November 2023.<br><br>EXPOSURES: Exposures were dementia medications. Cohort 1 compared patients prescribed donepezil with those prescribed rivastigmine or galantamine using the new-user design. Cohort 2 compared memantine with donepezil, rivastigmine, or galantamine using the prevalent new-user design. In a sensitivity analysis, cohort 3 compared memantine with rivastigmine or galantamine only.<br><br>MAIN OUTCOMES AND MEASURES: New diagnosis of AMD.<br><br>RESULTS: There were 132&#x202f;846 individuals (mean [SD] age, 80.4 [7.6] years; 61.8% women; mean [SD] body mass index [BMI], 25.5 [4.6]) with a diagnosis of dementia included in cohort 1, 159&#x202f;419 individuals (mean [SD] age, 81.2 [7.6] years; 59.7% women; mean [SD] body mass index [BMI], 25.6 [4.7]) with a diagnosis of dementia included in cohort 2, and 92&#x202f;328 individuals with a diagnosis of dementia included in cohort 3 (mean [SD] age, 80.9 [7.7] years; 58.5% women; mean [SD] body mass index [BMI], 25.5 [4.7]). The adjusted hazard ratio (HR) for donepezil compared with rivastigmine or galantamine (cohort 1) was 0.95 (95% CI, 0.67-1.35). The adjusted HR for memantine compared with donepezil, rivastigmine, or galantamine (cohort 2) was 1.03 (95% CI, 0.83-1.27). The adjusted HR for memantine vs rivastigmine or galantamine only (cohort 3) was 1.24 (95% CI, 0.83-1.86).<br><br>CONCLUSIONS AND RELEVANCE: This cohort study of patients with dementia found no significant associations between memantine or donepezil compared with other dementia medications and the risk of development of AMD. Further research is recommended to examine any possible pathophysiological protective action of memantine and other dementia medications against the development of AMD.},
}
@article {pmid39445352,
year = {2025},
author = {Sadeghi, E and Valsecchi, N and Vupparaboina, SC and Mehrotra, K and Vupparaboina, KK and Bollepalli, SC and Sahel, JA and Eller, AW and Chhablani, J},
title = {Geographic atrophy progression secondary to age-related macular degeneration: Five years of follow-up.},
journal = {European journal of ophthalmology},
volume = {35},
number = {3},
pages = {996-1004},
doi = {10.1177/11206721241287252},
pmid = {39445352},
issn = {1724-6016},
mesh = {Humans ; Female ; Male ; *Geographic Atrophy/etiology/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; Disease Progression ; Follow-Up Studies ; Aged, 80 and over ; Visual Acuity/physiology ; *Macular Degeneration/complications/diagnosis ; Fluorescein Angiography/methods ; Aged ; Retrospective Studies ; Time Factors ; Fundus Oculi ; },
abstract = {PurposeTo study the progression of geographic atrophy (GA) secondary to age-related macular degeneration over a five-year follow-up.MethodsEyes with GA included to assess demographic data, yearly optical coherence tomography (OCT) findings and the GA growth rate on infra-red (IR) images.ResultsA total of 41 eyes of 29 patients were included with a mean age of 81.76 ± 6.37 at baseline, and 65.51% were females. Over five years, there was a significant increase in the mean GA area from 8.44 ± 8.98 mm[2] to 13.32 ± 10.07 mm[2] (P < 0.001), with an annual growth rate of 1.14 ± 0.78 mm[2]. The annual growth rates in females were slightly higher compared to males (1.29 ± 0.89 mm2 vs 0.96 ± 0.49 mm2, p = 0.569), and in smokers was slightly higher than non-smokers (1.35 ± 0.85 mm2 vs 0.94 ± 0.66 mm2, p = 0.100). Larger GA areas at the baseline showed higher GA progression in mm[2] per year (P = 0.04). Smaller GA areas and fovea-spared GA at the baseline exhibited a larger percentage increase (P < 0.001 and P = 0.015, respectively). There was a lower GA progression rate in eyes with outer retinal tubulations (ORT) (P = 0.027), yet no significant correlation was found between GA progression and other OCT features.ConclusionsSmaller, fovea-sparing GA eyes experienced a more substantial proportional increase over five years. Also, The presence of ORT was associated with a slower rate of GA progression. Additionally, we observed a trend of faster GA growth in smokers and female genders.},
}
@article {pmid39444820,
year = {2024},
author = {Fan, S and Shi, XY and Li, X and Li, J and Yu, SP},
title = {Vitamin D levels and risk of ocular disorders: insights from bidirectional and multivariable Mendelian randomization analysis.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1431170},
pmid = {39444820},
issn = {2296-858X},
abstract = {PURPOSE: This study aimed to assess the causal relationships between vitamin D levels and ocular disorders.<br><br>METHODS: Independent genetic variables were obtained from genome-wide association studies (GWAS) and publicly available databases. The summary statistics for 25-hydroxyvitamin D (25(OH)D) were obtained from two large-scale GWAS studies, with sample sizes of 324,105 and 417,580 European individuals. The genetic variants of myopia, primary open angle glaucoma (POAG), anterior iridocyclitis, senile cataract, diabetic retinopathy (DR), retinal vein occlusion (RVO), wet age-related macular degeneration (WAMD) and optic neuritis were extracted from the latest release of FinnGen consortium, which contains genome data from Finnish participants. Subsequently, Mendelian randomization (MR) analyses were conducted to obtain effect estimates. Additionally, we performed multivariable MR analysis and mediation analysis to validate the results.<br><br>RESULTS: In the discovery dataset, genetically predicted vitamin D concentration was found to be causally associated with an increased risk of WAMD, (odd ratio (OR)&#x2009;=&#x2009;1.35, 95% confidence interval (CI)&#x2009;=&#x2009;1.09-1.67, P IVW =&#x2009;0.005). However, no causal effects of genetically predisposed vitamin D levels on the risk of most types of ocular disorders were observed. Reverse MR revealed no causal relationships between the ocular diseases and vitamin D concentrations. The MR analyses of the validation dataset yielded consistent results. Additionally, the causal effect of vitamin D levels on the risk of WAMD remained significant after adjusting for potential confounders in the multivariable MR analysis (OR&#x2009;=&#x2009;1.86, 95% CI&#x2009;=&#x2009;1.26-2.73, P IVW =&#x2009;0.002).<br><br>CONCLUSION: Our MR analysis results provide robust evidence of a causal relationship between genetically predicted 25(OH)D levels and an increased risk of WAMD in European population. These findings offer important insights into the management and control of ocular disorders.},
}
@article {pmid39444813,
year = {2024},
author = {Yang, J and Wu, B and Wang, J and Lu, Y and Zhao, Z and Ding, Y and Tang, K and Lu, F and Ma, L},
title = {Dry age-related macular degeneration classification from optical coherence tomography images based on ensemble deep learning architecture.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1438768},
pmid = {39444813},
issn = {2296-858X},
abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is a retinal disease, which has been the third leading cause of vision loss. But current AMD classification technologies did not focus on the classification of early stage. This study aimed to develop a deep learning architecture to improve the classification accuracy of dry AMD, through the analysis of optical coherence tomography (OCT) images.<br><br>METHODS: We put forward an ensemble deep learning architecture which integrated four different convolution neural networks including ResNet50, EfficientNetB4, MobileNetV3 and Xception. All networks were pre-trained and fine-tuned. Then diverse convolution neural networks were combined. To classify OCT images, the proposed architecture was trained on the dataset from Shenyang Aier Excellence Hospital. The number of original images was 4,096 from 1,310 patients. After rotation and flipping operations, the dataset consisting of 16,384 retinal OCT images could be established.<br><br>RESULTS: Evaluation and comparison obtained from three-fold cross-validation were used to show the advantage of the proposed architecture. Four metrics were applied to compare the performance of each base model. Moreover, different combination strategies were also compared to validate the merit of the proposed architecture. The results demonstrated that the proposed architecture could categorize various stages of AMD. Moreover, the proposed network could improve the classification performance of nascent geographic atrophy (nGA).<br><br>CONCLUSION: In this article, an ensemble deep learning was proposed to classify dry AMD progression stages. The performance of the proposed architecture produced promising classification results which showed its advantage to provide global diagnosis for early AMD screening. The classification performance demonstrated its potential for individualized treatment plans for patients with AMD.},
}
@article {pmid39444793,
year = {2024},
author = {Li, J and Wang, K and Starodubtseva, MN and Nadyrov, E and Kapron, CM and Hoh, J and Liu, J},
title = {Complement factor H in molecular regulation of angiogenesis.},
journal = {Medical review (2021)},
volume = {4},
number = {5},
pages = {452-466},
pmid = {39444793},
issn = {2749-9642},
abstract = {Angiogenesis, the process of formation of new capillaries from existing blood vessels, is required for multiple physiological and pathological processes. Complement factor H (CFH) is a plasma protein that inhibits the alternative pathway of the complement system. Loss of CFH enhances the alternative pathway and increases complement activation fragments with pro-angiogenic capacity, including complement 3a, complement 5a, and membrane attack complex. CFH protein contains binding sites for C-reactive protein, malondialdehyde, and endothelial heparan sulfates. Dysfunction of CFH prevents its interaction with these molecules and initiates pro-angiogenic events. Mutations in the CFH gene have been found in patients with age-related macular degeneration characterized by choroidal neovascularization. The Cfh-deficient mice show an increase in angiogenesis, which is decreased by administration of recombinant CFH protein. In this review, we summarize the molecular mechanisms of the anti-angiogenic effects of CFH and the regulatory mechanisms of CFH expression. The therapeutic potential of recombinant CFH protein in angiogenesis-related diseases has also been discussed.},
}
@article {pmid39443741,
year = {2025},
author = {Haruta, M and Dake, S and Yoshida, S},
title = {Multiple retinal vein thrombi after an intravitreal aflibercept 8 mg injection for age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {Suppl 1},
pages = {91},
pmid = {39443741},
issn = {1476-5454},
}
@article {pmid39442754,
year = {2025},
author = {Curtin, K and Stein, JD and Stagg, BC and Fino, N and Conley, M and Johnson, T and Patil, A and Paulson, C and Pompoco, C and Wirostko, BM},
title = {Identifiable Historic and Observable Factors May Predict Progression to Exfoliation Glaucoma in Newly Diagnosed Exfoliation Patients.},
journal = {Ophthalmology. Glaucoma},
volume = {8},
number = {2},
pages = {133-142},
pmid = {39442754},
issn = {2589-4196},
support = {K23 EY032577/EY/NEI NIH HHS/United States ; R01 RR021746/RR/NCRR NIH HHS/United States ; },
mesh = {Humans ; *Exfoliation Syndrome/diagnosis/physiopathology/epidemiology/complications ; Retrospective Studies ; Male ; Female ; Disease Progression ; Aged ; *Intraocular Pressure/physiology ; Middle Aged ; Risk Factors ; Follow-Up Studies ; *Glaucoma, Open-Angle/diagnosis/physiopathology ; Visual Fields/physiology ; Aged, 80 and over ; },
abstract = {OBJECTIVE: To identify clinical factors associated with conversion to exfoliation glaucoma (XFG) in exfoliation syndrome (XFS) patients who are most at risk of progression to XFG within 3 years for increased surveillance and early preventive interventions.<br><br>DESIGN: A retrospective patient cohort study design was employed.<br><br>SUBJECTS: A source population of XFS patients &#x2265; 50 years was identified from electronic medical records in the Utah Population Database. From this, 487 study patients with one or more dilated eye examinations before chart-confirmed XFS onset in 2011 or later and &#x2265; 3 years of subsequent eye examinations were selected for study.<br><br>METHODS: We implemented binomial linear mixed models with L1-penalized estimation to select variables associated with conversion. Models included a random intercept to account for within-patient correlation for eye-level data. Candidate demographic, lifestyle, systemic, and ocular comorbidities data were obtained, and diagnoses were categorized as binary (history or no history). These potential factors between conversion and nonconversion patients were used in model selection of variables jointly predictive of conversion. Odds ratios and confidence intervals were calculated using the link logit.<br><br>MAIN OUTCOME MEASURES: To determine the main outcome of conversion to XFG following an index diagnosis of XFS compared with nonconversion within 3 years, clinical records of each subject's left and right eyes were assessed to confirm XFS and date of onset and date of XFG onset, if conversion occurred. Clinical measurements (e.g., intraocular pressure [IOP], cup-to-disc ratio, provider notes, and IOP-lowering procedures and medications) were used to corroborate conversion status.<br><br>RESULTS: Eighteen variables jointly predicted XFG conversion within 3 years correctly in 71% of patient eyes. The odds of conversion were the highest for exudative age-related macular degeneration (AMD), 2.3-fold (P&#xa0;=&#xa0;0.004). Other predictive variables included nonexudative AMD (P&#xa0;=&#xa0;0.05), primary open angle glaucoma (P&#xa0;<&#xa0;0.001), obstructive sleep apnea (P&#xa0;=&#xa0;0.03), and ocular hypertension (P&#xa0;=&#xa0;0.003) diagnosed before XFS onset.<br><br>CONCLUSIONS: We determined a set of clinically relevant factors that predicted which newly diagnosed XFS patients progressed to XFG within 3 years. A planned validation will independently confirm if these prognostic indicators hold promise in other settings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39442014,
year = {2025},
author = {Lee, JH and Park, SM and Kim, JH},
title = {FLUID RESOLUTION WITHOUT SHORTENING INJECTION INTERVAL DURING SUBRETINAL FLUID-TOLERATING TREATMENT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {2},
pages = {178-187},
pmid = {39442014},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; *Subretinal Fluid/diagnostic imaging ; Male ; Female ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Intravitreal Injections ; Aged ; Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Fluorescein Angiography/methods ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Fundus Oculi ; },
abstract = {PURPOSE: To investigate the incidence and factors associated with subretinal fluid (SRF) resolution during SRF-tolerating treatment in patients with neovascular age-related macular degeneration.<br><br>METHODS: This retrospective study included patients diagnosed with neovascular age-related macular degeneration who exhibited fovea-involving residual SRF persisting for at least 6 months during aflibercept treatment. Patients who showed SRF resolution despite maintaining the injection intervals were included in the resolution group, while those who exhibited persisting SRF throughout the study period were included in the nonresolution group. The incidence and associated factors of SRF resolution without reducing the injection interval were evaluated. Furthermore, the frequency of successfully extending the injection intervals while maintaining SRF resolution was identified.<br><br>RESULTS: In total, 65 patients with neovascular age-related macular degeneration were included (32 and 33 in the resolution and nonresolution groups, respectively). When compared with the nonresolution group, the resolution group showed a lower mean height of SRF (67.7 &#xb1; 33.4 vs. 109.9 &#xb1; 44.9 &#xb5; m, P < 0.001) and a lower maximum height of SRF (138.3 &#xb1; 88.6 vs. 176.2 &#xb1; 76.9 &#xb5; m, P = 0.034). In multivariate analysis, the mean SRF height (P = 0.001), maximum SRF height (P = 0.006), and interval of anti-vascular endothelial growth factor injections (P = 0.023) were significantly associated with the resolution of SRF. In the resolution group, 14 patients (43.8%) successfully expanded the injection interval.<br><br>CONCLUSION: During SRF-tolerating treatment for neovascular age-related macular degeneration, a substantial proportion of patients exhibited resolution of fluid without shortening the injection interval. Patients with lesser residual SRF during treatment were more likely to achieve fluid resolution. After SRF resolution, injection intervals can be extended in more than 40% of patients.},
}
@article {pmid39441289,
year = {2024},
author = {Xu, F and Xu, Z and Li, M},
title = {INTRAVITREAL INJECTION CONBERCEPT IMPROVES THE BEST-CORRECTED VISUAL ACUITY IN PATIENTS WITH WET AGE-RELATED MACULAR EDEMA.},
journal = {Georgian medical news},
volume = {},
number = {352-353},
pages = {165-167},
pmid = {39441289},
issn = {1512-0112},
mesh = {Humans ; *Visual Acuity/drug effects ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Intravitreal Injections ; Female ; Male ; Aged ; Macular Edema/drug therapy/physiopathology ; Treatment Outcome ; Middle Aged ; Aged, 80 and over ; Wet Macular Degeneration/drug therapy/physiopathology ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; },
abstract = {UNLABELLED: The aim of the study was to investigate the value of intravitreal injection conbercept on the best-corrected visual acuity in patients with age-related macular edema.<br><br>METHODS: In this study, 114 patients (114 eyes) were treated with intravitreal injection of Conbercept in our hospital from August 2020 to January 2022. According to the clinical effect after treatment, they were divided into effective group (78 cases, 78 eyes) and ineffective group (36 cases, 36 eyes). All patients were continuously treated with intravitreal injection of Conbercept. The best corrected visual acuity (BCVA) was compared between the two groups.<br><br>RESULTS: Before treatment, the BCVA was compared between the effective group and the ineffective group (P>0.05). After 1, 2, and 3 times of treatment, the BCVA values of the effective group were lower than those of the ineffective group, and the BCVA changes of the effective group before and after treatment were greater than those of the ineffective group (P<0.05).<br><br>CONCLUSION: The BCVA values of the effective group were lower than those of the ineffective group, and the BCVA changes of the effective group before and after treatment were greater than those of the ineffective group, suggesting that conbercept can improve the visual acuity of patients with macular edema caused by wet age-related macular degeneration.},
}
@article {pmid39440146,
year = {2024},
author = {Yoganathan, P and Hurley, B and Merkur, A and Andrews, C and Pereira, JA and Moniz, LS},
title = {Physical, Psychosocial, and Practical Burden of Patients Receiving Care for Age-Related Macular Degeneration in Canada: A Mixed-Methods Qualitative Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {2951-2967},
pmid = {39440146},
issn = {1177-5467},
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. Documentation of the disease's description and treatment experience of Canadian patients is limited but of interest given the aging population and resultant implications for healthcare systems. A mixed-methods study was conducted to understand the challenges experienced by patients living in Canada with AMD to identify areas of need and for potential reform.<br><br>PATIENTS AND METHODS: Canadian residents with wet or dry AMD were eligible for participation in an online survey and one-on-one telephone interview regarding their disease experience. Participants were recruited via a not-for-profit stakeholder organization and an ophthalmology clinic. Surveys were completed from January-June 2020 and interviews were conducted from November-December 2020, with findings reported using descriptive statistics and thematic analysis, respectively.<br><br>RESULTS: Findings from 303 survey responses and 20 interviews were analyzed. Most participants indicated their vision loss negatively impacts their ability to conduct daily activities (eg, self care, driving) and leads to constant worry, loneliness, and/or isolation. Participants frequently reported requiring caregiver support, often for eye appointment travel or everyday tasks. Regardless of AMD type, participants reported having several appointments each year, and that time spent travelling to/from and waiting at appointments and related costs were considerable. Although participants receiving anti-vascular endothelial growth factor injections valued treatment, the experience added additional burden related to anxiety, fear, pain, and even greater reliance on caregivers. Many participants indicated they felt poorly informed about their disease and treatment options, particularly at diagnosis, which increased their emotional burden.<br><br>CONCLUSION: Patients with AMD living in Canada experience a significant and persistent mental, physical, and financial burden as a direct result of their disease. Improvements to provision of disease-related information, support of daily activities and appointment attendance, and the overall treatment experience could substantially enhance outcomes among the growing population of patients with AMD.},
}
@article {pmid39435874,
year = {2025},
author = {Yu, J and Li, F and Liu, M and Zhang, M and Liu, X},
title = {Application of Artificial Intelligence in the Diagnosis, Follow-Up and Prediction of Treatment of Ophthalmic Diseases.},
journal = {Seminars in ophthalmology},
volume = {40},
number = {3},
pages = {173-181},
doi = {10.1080/08820538.2024.2414353},
pmid = {39435874},
issn = {1744-5205},
mesh = {Humans ; *Artificial Intelligence ; *Eye Diseases/diagnosis/therapy ; *Diagnostic Techniques, Ophthalmological ; Follow-Up Studies ; },
abstract = {PURPOSE: To describe the application of artificial intelligence (AI) in ophthalmic diseases and its possible future directions.<br><br>METHODS: A retrospective review of the literature from PubMed, Web of Science, and Embase databases (2019-2024).<br><br>RESULTS: AI assists in cataract diagnosis, classification, preoperative lens calculation, surgical risk, postoperative vision prediction, and follow-up. For glaucoma, AI enhances early diagnosis, progression prediction, and surgical risk assessment. It detects diabetic retinopathy early and predicts treatment effects for diabetic macular edema. AI analyzes fundus images for age-related macular degeneration (AMD) diagnosis and risk prediction. Additionally, AI quantifies and grades vitreous opacities in uveitis. For retinopathy of prematurity, AI facilitates disease classification, predicting disease occurrence and severity. Recently, AI also predicts systemic diseases by analyzing fundus vascular changes.<br><br>CONCLUSIONS: AI has been extensively used in diagnosing, following up, and predicting treatment outcomes for common blinding eye diseases. In addition, it also has a unique role in the prediction of systemic diseases.},
}
@article {pmid39435619,
year = {2025},
author = {Jin, Q and Wang, S and Yao, Y and Jiang, Q and Li, K},
title = {The gut-eye axis: from brain neurodegenerative diseases to age-related macular degeneration.},
journal = {Neural regeneration research},
volume = {20},
number = {10},
pages = {2741-2757},
pmid = {39435619},
issn = {1673-5374},
abstract = {Age-related macular degeneration is a serious neurodegenerative disease of the retina that significantly impacts vision. Unfortunately, the specific pathogenesis remains unclear, and effective early treatment options are consequently lacking. The microbiome is defined as a large ecosystem of microorganisms living within and coexisting with a host. The intestinal microbiome undergoes dynamic changes owing to age, diet, genetics, and other factors. Such dysregulation of the intestinal flora can disrupt the microecological balance, resulting in immunological and metabolic dysfunction in the host, and affecting the development of many diseases. In recent decades, significant evidence has indicated that the intestinal flora also influences systems outside of the digestive tract, including the brain. Indeed, several studies have demonstrated the critical role of the gut-brain axis in the development of brain neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Similarly, the role of the "gut-eye axis" has been confirmed to play a role in the pathogenesis of many ocular disorders. Moreover, age-related macular degeneration and many brain neurodegenerative diseases have been shown to share several risk factors and to exhibit comparable etiologies. As such, the intestinal flora may play an important role in age-related macular degeneration. Given the above context, the present review aims to clarify the gut-brain and gut-eye connections, assess the effect of intestinal flora and metabolites on age-related macular degeneration, and identify potential diagnostic markers and therapeutic strategies. Currently, direct research on the role of intestinal flora in age-related macular degeneration is still relatively limited, while studies focusing solely on intestinal flora are insufficient to fully elucidate its functional role in age-related macular degeneration. Organ-on-a-chip technology has shown promise in clarifying the gut-eye interactions, while integrating analysis of the intestinal flora with research on metabolites through metabolomics and other techniques is crucial for understanding their potential mechanisms.},
}
@article {pmid39434920,
year = {2024},
author = {Shaw, EM and Tate, AJ and Periasamy, R and Lipinski, DM},
title = {Characterization of drusen formation in a primary porcine tissue culture model of dry AMD.},
journal = {Molecular therapy. Methods &amp; clinical development},
volume = {32},
number = {4},
pages = {101331},
pmid = {39434920},
issn = {2329-0501},
abstract = {Age-related macular degeneration (AMD) affects millions of individuals worldwide and is a leading cause of blindness in the elderly. In dry AMD, lipoproteinaceous deposits called drusen accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane, leading to impairment of oxygen and nutrient trafficking to the neural retina, and degeneration of the overlying photoreceptor cells. Owing to key differences in human and animal ocular anatomy and the slowly progressing nature of the disease, AMD is not easily modeled in vivo. In this study, we further characterize a "drusen-in-a-dish" primary porcine RPE model system by employing vital lipid staining to monitor sub-RPE deposition over time in monolayers of cells cultured on porous transwell membranes. We demonstrate for the first time using a semi-automated image analysis pipeline that the number and size of sub-RPE deposits increases gradually but significantly over time and confirm that sub-RPE deposits grown in culture immunostain positive for multiple known components found in human drusen. As a result, we propose that drusen-in-a-dish cell culture models represent a high-throughput and cost-scalable alternative to animal models in which to study the pathobiology of drusen accumulation and may serve as useful tools for screening novel therapeutics aimed at treating dry AMD.},
}
@article {pmid39434578,
year = {2024},
author = {Moon, H and Kang, HG and Lee, J and Lee, CS and Kim, M and Byeon, SH and Kim, SS},
title = {Predictive Factors for Submacular Hemorrhage in Age-related Macular Degeneration: A Retrospective Study.},
journal = {Korean journal of ophthalmology : KJO},
volume = {38},
number = {6},
pages = {471-479},
pmid = {39434578},
issn = {2092-9382},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Tomography, Optical Coherence/methods ; *Intravitreal Injections ; Aged ; *Retinal Hemorrhage/diagnosis/etiology/drug therapy ; Cross-Sectional Studies ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Fluorescein Angiography/methods ; Risk Factors ; Wet Macular Degeneration/diagnosis/drug therapy/complications ; Visual Acuity ; Fundus Oculi ; Ranibizumab/administration &amp; dosage ; Follow-Up Studies ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: Little is known about the major risk factors for submacular hemorrhage (SMH). This study aimed to evaluate the factors associated with SMH in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy receiving three consecutive loading doses of intravitreal aflibercept or ranibizumab injections.<br><br>METHODS: This retrospective cross-sectional study included 48 patients diagnosed with nAMD and polypoidal choroidal vasculopathy who completed three loading doses under a treat-and-extend regimen. Patients were divided into the SMH group and the non-SMH group (age- and sex-matched without SMH), with 24 patients in each group. Intravitreal injections, agents, and optical coherence tomography (OCT) features were compared.<br><br>RESULTS: In the SMH group, SMH occurred approximately 3.29 years after post-nAMD diagnosis. The non-SMH group received more intravitreal injections of aflibercept and brolucizumab during the follow-up period after the initial loading phase. The SMH group exhibited a higher prevalence of serous/hemorrhagic pigment epithelial detachments (PEDs) at the last visit before SMH occurrence compared to the non-SMH group. Patients with a PED increase in the past two visits showed a higher tendency in the SMH group. No other OCT features significantly correlated with SMH development.<br><br>CONCLUSIONS: The presence of serous/hemorrhagic PEDs may indicate a higher risk of SMH, and eyes with these features should be closely monitored to prevent sudden and devastating visual loss caused by SMH.},
}
@article {pmid39433679,
year = {2025},
author = {Chang, K and Chen, J and Rajagopalan, A and Chen, DF and Cho, KS},
title = {Testing Visual Function by Assessment of the Optomotor Reflex in Glaucoma.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2858},
number = {},
pages = {219-227},
pmid = {39433679},
issn = {1940-6029},
mesh = {Animals ; *Glaucoma/physiopathology/diagnosis ; Mice ; *Disease Models, Animal ; *Visual Acuity ; Humans ; Eye Movements/physiology ; Contrast Sensitivity/physiology ; Vision Tests/methods ; Zebrafish/physiology ; Reflex/physiology ; },
abstract = {Optomotor response/reflex (OMR) is a fast and efficient first-in-line visual screening method, especially for rodents. It has the potential to evaluate both the scotopic and photopic visions of nonrestrained animals through tracking head movement, providing a quantitative estimate of visual functions. In restrained animals, optokinetic response (OKR), compensatory eye movements for visual shifts in the surroundings, is utilized. Both OMR and OKR capitalize on an individual's innate reflex to stabilize images for the purpose of capturing clear vision. The two reflexes have similar reliability when evaluating stimulus luminance, contrast, spatial frequency, and velocity. They have emerged as powerful tools to evaluate the efficacy of pharmacological treatments and phenotypes of subjects undergoing study. With OMR and OKR accurately assessing visual acuity (VA) as well as contrast sensitivity (CS), the gold standards for measuring clinical vision, they provide reliable and easily accessible results that further eye and brain research. These methods of sight evaluation have been used in multiple animal models, particularly mice and zebrafish. Through OMR assays, these animal models have been utilized to investigate retinal degenerative diseases, helping researchers differentiate between worsening stages. Alongside tests such as optical coherence tomography (OCT), OMR provides confirmation of visual status, where increased OMR function often correlates with improved visual status. OMR has continued to be used outside of glaucoma in various retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy, and age-related macular degeneration.In this chapter, we will introduce the concept and application of visual stimulus-induced head or eye reflex movement in different animal species and experimental models of eye diseases, such as glaucoma and other neurodegenerative disorders, and in patients with glaucoma.},
}
@article {pmid39433211,
year = {2025},
author = {Hansman, DS and Du, J and Casson, RJ and Peet, DJ},
title = {Eye on the horizon: The metabolic landscape of the RPE in aging and disease.},
journal = {Progress in retinal and eye research},
volume = {104},
number = {},
pages = {101306},
pmid = {39433211},
issn = {1873-1635},
support = {R01 EY034364/EY/NEI NIH HHS/United States ; U01 EY034591/EY/NEI NIH HHS/United States ; R01 EY031324/EY/NEI NIH HHS/United States ; R01 EY032462/EY/NEI NIH HHS/United States ; R01 EY031720/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Aging/physiology/metabolism ; Energy Metabolism/physiology ; Macular Degeneration/metabolism ; Oxidative Stress/physiology ; *Retinal Diseases/metabolism ; *Retinal Pigment Epithelium/metabolism ; },
abstract = {To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress - all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.},
}
@article {pmid39432927,
year = {2025},
author = {Wu, S and Wang, K and Lv, Q and Tan, M},
title = {Enhanced therapeutic intervention of curcumin loaded in exosomes derived from milk in alleviating retinal pigment epithelial cells damage.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {245},
number = {},
pages = {114325},
doi = {10.1016/j.colsurfb.2024.114325},
pmid = {39432927},
issn = {1873-4367},
mesh = {*Curcumin/pharmacology/chemistry ; *Exosomes/metabolism/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; Animals ; Humans ; *Milk/chemistry ; *Oxidative Stress/drug effects ; Reactive Oxygen Species/metabolism ; Hydrogen Peroxide/pharmacology ; Iodates ; Tumor Necrosis Factor-alpha/metabolism ; Antioxidants/pharmacology/chemistry ; Interleukin-1beta/metabolism ; Epithelial Cells/drug effects/metabolism ; Cell Line ; Cell Survival/drug effects ; Macular Degeneration/drug therapy/pathology/metabolism ; },
abstract = {The macula, a small but highly important area in the retina, is crucial for healthy vision. Age-related macular degeneration is responsible for approximately 8.7 % of blindness worldwide, and affected individuals are burgeoning. The age-related macular degeneration is often triggered by oxidative stress and excessive inflammation that damage the retinal pigment epithelial cells in the macula. Curcumin, a potent antioxidant and anti-inflammatory carotenoid, is hampered by low compatibility and stability issues in food science. Innovatively, this study harnessed milk-derived exosomes as a novel delivery method yielding a curcumin-infused system (curcumin@exosome) to increase its biocompatibility and stability. This fusion not only curbed excessive reactive oxygen species but also neutralized H2O2-induced mitochondrial disruption in cellular models. It revitalized retinal pigment epithelial cells, reverting their function near to baseline in vitro. The curcumin@exosome outshined in subduing pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β induced by sodium iodate. This study illuminates that the curcumin@exosome is promise as a therapeutic intervention for retinal ailments marked by oxidative and inflammatory distress.},
}
@article {pmid39432659,
year = {2024},
author = {Onagawa, S and Miura, M},
title = {Occlusive retinal vasculitis and scleritis following brolucizumab treatment: A case report.},
journal = {Medicine},
volume = {103},
number = {42},
pages = {e40154},
pmid = {39432659},
issn = {1536-5964},
mesh = {Humans ; *Scleritis/chemically induced ; Male ; Aged ; *Retinal Vasculitis/chemically induced/diagnosis ; *Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; *Intravitreal Injections ; Macular Degeneration/drug therapy ; },
abstract = {RATIONALE: Brolucizumab is an anti-vascular endothelial growth factor agent. Clinical trials have demonstrated excellent efficacy of brolucizumab for neovascular age-related macular degeneration in terms of both visual and anatomic outcomes. However, compared with conventional anti-vascular endothelial growth factor therapy, this new treatment has a higher incidence of complications, particularly the development of occlusive retinal vasculitis. In this case report, we describe a patient who developed occlusive retinal vasculitis following brolucizumab treatment for age-related macular degeneration, followed by scleritis 141 days later.<br><br>PATIENT CONCERNS: A 67-year-old Japanese man with a diagnosis of polypoidal choroidal vasculopathy in his right eye has received 18 intravitreal injections of aflibercept in the past 4 years. Because of a decline in treatment efficacy, intravitreal brolucizumab injection (IVBr) was initiated. However, 17 days after the second IVBr, the patient developed extensive occlusive retinal vasculitis with intraocular inflammation.<br><br>DIAGNOSIS: Occlusive retinal vasculitis in the right eye was diagnosed as a complication of brolucizumab therapy.<br><br>INTERVENTIONS: Corticosteroid treatment was initiated.<br><br>OUTCOMES: The occlusive retinal vasculitis resolved 121 days after the second IVBr, and corticosteroid treatment was discontinued on day 138. However, on day 158 after the second IVBr, scleritis with intraocular inflammation developed. By day 184 after the second IVBr, both the scleritis and intraocular inflammation had resolved with the resumption of topical corticosteroid treatment.<br><br>LESSONS: This case underscores the potential for brolucizumab-induced scleritis and emphasizes the importance of recognizing and promptly managing this complication. Furthermore, it highlights the need for long-term careful follow-up in patients who develop occlusive retinal vasculitis after brolucizumab treatment.},
}
@article {pmid39431040,
year = {2024},
author = {Sevik, MO and Tiras, NZ and Aykut, A and Yigit, DD and Sahin, O},
title = {Real-life neovascular AMD treatment considering reimbursement in Turkiye: One-year comparison of switching to intravitreal ranibizumab or aflibercept after treatment failure with three loading intravitreal bevacizumab injections.},
journal = {Northern clinics of Istanbul},
volume = {11},
number = {5},
pages = {451-459},
pmid = {39431040},
issn = {2536-4553},
abstract = {OBJECTIVE: To compare one-year anatomical and functional results of switching to an on-label intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent (intravitreal ranibizumab [IVR] or aflibercept [IVA]) after treatment failure with three loading doses of off-label intravitreal bevacizumab (IVB), which is mandatory in the treatment of neovascular age-related macular degeneration (nAMD) to get reimbursement from Social Security Institution in Turkiye.<br><br>METHODS: This comparative, real-life, retrospective cohort study included treatment-na&#xef;ve nAMD patients treated starting with three loading doses of IVB, switched to three loading doses of IVR and IVA due to treatment failure after IVB loading, and followed up one year with a treat-and-extend (T&amp;E) protocol with 2-week extension/shortening intervals. The primary outcomes were changes in best-corrected visual acuity (BCVA; logMAR) and central macular thickness (CMT, &#xb5;m) one year after the switch, and the secondary outcomes were maximum treatment intervals, number of injections, and disease activity rates.<br><br>RESULTS: The mean age (72.9&#xb1;8.2 and 72.2&#xb1;6.7, p=0.677) and gender (60.0% and 47.4% females, p=0.398) were similar among the IVR (35 eyes/patients) and IVA (38 eyes/patients) groups. The median BCVA and CMT were significantly improved during the study period (p<0.001) with no significant intergroup differences. The ratio of 4-, 6-, 8-, 10-, and 12-week maximum treatment intervals were 28.6%, 17.1%, 14.3%, 8.6%, and 31.4% in the IVR, and 13.2%, 15.8%, 21.1%, 15.8%, and 34.2% in the IVA group (p=0.492). The median (IQR) number of injections in the IVA group (8 [7-9]) was significantly lower than the IVR group (9 [8-12]) during the one-year T&amp;E period (p=0.026). The disease activity rates were 34.3% and 26.4% one month (p=0.610) and 37.1% and 21.1% one year (p=0.195) after the switch in IVR and IVA groups.<br><br>CONCLUSION: This real-life comparison study indicates that, after the treatment failure with three loading doses of IVB, switching to either on-label anti-VEGF agent can be regarded as comparable considering functional and anatomical results. However, although maximum treatment intervals were not significantly different, fewer injections were required with aflibercept during the one-year T&amp;E follow-up period.},
}
@article {pmid39430909,
year = {2024},
author = {Pericak, J and Chin, EK and Almeida, DRP},
title = {Early SUSVIMO in Neovascular Age-Related Macular Degeneration: Real Word Case Report and Clinical Implications.},
journal = {International medical case reports journal},
volume = {17},
number = {},
pages = {849-853},
pmid = {39430909},
issn = {1179-142X},
abstract = {PURPOSE: The current standard of care for neovascular age-related macular degeneration is serial vascular endothelial growth factor (VEGF) inhibitor intravitreal injections at varying treatment intervals. SUSVIMO is a port-delivery system of ranibizumab that serves as an alternative, lower-maintenance treatment.<br><br>METHODS: A case report from a retinal surgery clinic describing the ocular findings, diagnostic workup, and alternative treatment for an 80-year-old man presenting with new-onset neovascular age-related macular degeneration.<br><br>RESULTS: Resolved foveal thickness, macular volume, and subretinal fluid after SUSVIMO implantation OD. The patient showed a better response to SUSVIMO than to previous anti-VEGF injections. Before the first refill, the patient began to experience subretinal fluid; however, it was resolved after the refill.<br><br>CONCLUSION: Although effective, real-world management of neovascular age-related macular degeneration is associated with an extensive treatment burden that can compromise treatment adherence. Herein, we describe how the port delivery system (PDS; SUSVIMO) - a refillable ocular implant that can continuously deliver a novel formulation of ranibizumab with refills possible at six months or longer - is a viable early therapy that mitigates the treatment burden of intravitreal injections.},
}
@article {pmid39430310,
year = {2024},
author = {Wang, Y and Yuan, B and Liu, W and Cui, J and Zhou, X and Yuan, L and Deng, Z and Li, Y and Yuan, X},
title = {The Xaliproden Nanoscale Zirconium-Porphyrin Metal-Organic Framework (XAL-NPMOF) Promotes Photoreceptor Regeneration Following Oxidative and Inflammatory Insults.},
journal = {International journal of nanomedicine},
volume = {19},
number = {},
pages = {10387-10400},
pmid = {39430310},
issn = {1178-2013},
mesh = {Animals ; *Zebrafish ; *Zirconium/chemistry/pharmacology ; Humans ; *Porphyrins/chemistry/pharmacology ; *Metal-Organic Frameworks/chemistry/pharmacology ; *Human Umbilical Vein Endothelial Cells/drug effects ; *Regeneration/drug effects ; Macular Degeneration/drug therapy ; Oxidative Stress/drug effects ; Nanoparticles/chemistry ; Inflammation/drug therapy ; Photoreceptor Cells, Vertebrate/drug effects ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is becoming the leading cause of blindness in the aged population. The death of photoreceptors is the principal event which is lack of curative treatment. Xaliproden, a highly selective synthetic 5-OH-tryptamine (5HT) 1A receptor agonist, has the neuroprotective potential. However, its application has been limited by the insoluble formulation, low utilization efficiency and side effects caused by systemic administration.<br><br>METHODS: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was used as a skeleton and loaded with xaliproden (XAL) to prepare a novel kind of nanoparticle, namely, XAL-NPMOF. The human umbilical vein endothelial cells, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of XAL-NPMOF both in vitro and in vivo. A photoreceptor degeneration model was generated by intense light injury in adult zebrafish and XAL-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration, inflammatory response and visual function were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and optomotor response analysis.<br><br>RESULTS: Following a single XAL-NPMOF intraocular injection, the injured retina underwent the faster photoreceptor regeneration with a recovery of visual function via promoting cell proliferation, suppressing the inflammatory responses and increasing the expression of antioxidases.<br><br>CONCLUSION: As an amplifier, NPMOF can enhance the anti-inflammatory efficacy and neuroprotective effect of xaliproden. XAL-NPMOF could be a novel and convenient option for the treatment of AMD.},
}
@article {pmid39429384,
year = {2024},
author = {Sawazono, A and Funatsu, R and Terasaki, H and Mihara, N and Sakamoto, T},
title = {Polypoidal Choroidal Vasculopathy Complicated by Red Blood Cell-Coated Intraocular Lens: A Case Report.},
journal = {Cureus},
volume = {16},
number = {9},
pages = {e69639},
pmid = {39429384},
issn = {2168-8184},
abstract = {This study aimed to characterize the detailed multi-modal imaging findings of red blood cell (RBC)-coated intraocular lenses (IOLs). A 68-year-old patient with polypoidal choroidal vasculopathy underwent vitrectomy for subretinal and vitreous hemorrhage. Subsequently, RBC-coated IOL was diagnosed. The iris and IOL surface exhibited a reddish discoloration, while the fundus was completely obscured by slit-lamp examination and ultra-widefield scanning laser ophthalmoscopy. However, posterior segment optical coherence tomography (OCT) allowed visualization of retinal structures. Anterior segment OCT revealed no opacity in the optic part of the IOL in either eye, with comparable findings between both eyes. Given the high absorption spectrum of blood in the visible light range and its minimum absorption at approximately 1100 nm, RBC-coated IOLs may minimally affect anterior and posterior segment OCT images. Conversely, they significantly impair slit-lamp examination and direct fundus visualization. The discrepancy in imaging outcomes between fundus image and OCT could be a characteristic feature of RBC-coated IOLs. This may serve as a characteristic of RBC-coated IOLs. In cases of suspected IOL opacification or RBC-coated IOL following vitreous hemorrhage, anterior segment OCT can evaluate the IOL optic clarity. Additionally, comparing image quality between fundus photographs and posterior segment OCT may provide valuable diagnostic information.},
}
@article {pmid39429338,
year = {2024},
author = {Garg, D and Daigavane, S},
title = {Photobiomodulation in Ophthalmology: A Comprehensive Review of Bench-to-Bedside Research and Clinical Integration.},
journal = {Cureus},
volume = {16},
number = {9},
pages = {e69651},
pmid = {39429338},
issn = {2168-8184},
abstract = {Photobiomodulation (PBM), also known as low-level laser therapy, is an emerging therapeutic modality in ophthalmology, attracting increasing interest for its potential to manage a variety of ocular conditions. PBM employs low-energy light within the red and near-infrared spectrum to penetrate biological tissues, where it interacts with cellular chromophores. This interaction is believed to enhance mitochondrial function, boost adenosine triphosphate (ATP) production, and reduce oxidative stress, leading to improved cellular repair and tissue regeneration. Recent bench research has demonstrated PBM's efficacy in cellular and animal models, showing its ability to modulate inflammatory processes and promote healing in retinal and corneal diseases. For instance, in retinal models, PBM has been observed to reduce apoptosis and support cell survival under stress conditions. Similarly, studies in corneal models suggest that PBM can accelerate wound healing and reduce scarring. Clinical trials further corroborate these findings, revealing that PBM can enhance treatment outcomes in several ocular diseases, including age-related macular degeneration, diabetic retinopathy, and dry eye disease. Patients undergoing PBM have reported improvements in visual acuity, reduced retinal inflammation, and better tear film stability, highlighting its potential as an adjunctive therapy. This review also explores the integration of PBM into clinical practice, discussing current treatment protocols, safety considerations, and the latest advancements in PBM technology. By offering a holistic overview, the review aims to provide clinicians and researchers with valuable insights into PBM's role in modern ophthalmic care, emphasizing its potential to enhance treatment strategies and improve patient outcomes.},
}
@article {pmid39428594,
year = {2025},
author = {Arokiasamy, S and Balderstone, MJM and Shaik, F and Cristante, E and Moseley, TC and Madoo, A and Rizzi, M and Bainbridge, JW and Tsoyi, K and Rosas, IO and Whiteford, JR and De Rossi, G},
title = {QM107, a novel CD148 (RTP Type J) activating peptide therapy for treating neovascular age-related macular degeneration.},
journal = {British journal of pharmacology},
volume = {182},
number = {4},
pages = {951-968},
doi = {10.1111/bph.17362},
pmid = {39428594},
issn = {1476-5381},
support = {1558/59//Fight for Sight UK/ ; SGAFFS2203//Fight for Sight UK/ ; //Macular Society/ ; G-002397//Barts Charity/ ; MGU0313//Barts Charity/ ; RPGF1906\173//Dunhill Medical Trust/ ; //Queen Mary Innovations/ ; //William Harvey Research Foundation/ ; GR001526//Moorfields Eye Charity/ ; 19207/ARC_/Arthritis Research UK/United Kingdom ; 21177/ARC_/Arthritis Research UK/United Kingdom ; 23/0006514/DUK_/Diabetes UK/United Kingdom ; },
mesh = {Humans ; Animals ; *Macular Degeneration/drug therapy/metabolism ; Peptides/pharmacology ; Basigin/metabolism ; Male ; Cells, Cultured ; Mice ; Human Umbilical Vein Endothelial Cells/drug effects ; Neovascularization, Pathologic/drug therapy ; Mice, Inbred C57BL ; Cell Movement/drug effects ; },
abstract = {BACKGROUND AND PURPOSE: Angiogenesis is a pathological component of neovascular age-related macular degeneration. Current therapies, although successful, are prone to high levels of patient non-response and a loss of efficacy over time, indicating the need to explore other therapeutic avenues. We have shown that an interaction between syndecan-2 and the tyrosine phosphatase receptor CD148 (RTP Type J) results in the ablation of angiogenesis. Here we exploit this pathway to develop a peptide activator of CD148 as a therapy for neovascular age-related macular degeneration.<br><br>EXPERIMENTAL APPROACH: We tested a peptide (QM107) derived from syndecan-2 in a variety of angiogenesis models and a pre-clinical model of neovascular age-related macular degeneration. We assessed the toxicological and inflammatory profiles of QM107 and its stability in vitreous humour.<br><br>KEY RESULTS: QM107 inhibits angiogenesis in ex vivo sprouting assays and disrupts endothelial microcapillary formation via inhibition of cell migration. QM107 acts through CD148, leading to changes in GSK3A phosphorylation and &#x3b2;1 integrin activation. QM107 elicits a negligible inflammatory response and exhibits limited toxicity in cultured cells, and is stable in vitreous humour. Finally, we show proof of concept that QM107 blocks angiogenesis in vivo using a model of neovascular age-related macular degeneration.<br><br>CONCLUSION AND IMPLICATIONS: We have developed a CD148 activating peptide which shows promise in inhibiting angiogenesis in models of neovascular age-related macular degeneration. This treatment could either represent an alternative or augment existing therapies, and owing to its distinct mode of action be used in patients who do not respond to existing treatments.},
}
@article {pmid39426958,
year = {2024},
author = {Azuma, K and Suzuki, T and Kobayashi, K and Nagahara, M and Imai, H and Suga, A and Iwata, T and Shiraya, T and Aihara, M and Ueta, T},
title = {Retinal pigment epithelium-specific ablation of GPx4 in adult mice recapitulates key features of geographic atrophy in age-related macular degeneration.},
journal = {Cell death &amp; disease},
volume = {15},
number = {10},
pages = {763},
pmid = {39426958},
issn = {2041-4889},
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; *Geographic Atrophy/metabolism/pathology/genetics ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism/genetics ; Mice ; *Macular Degeneration/pathology/metabolism/genetics ; Disease Models, Animal ; Ferroptosis/genetics ; Mice, Inbred C57BL ; Mice, Knockout ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population, particularly the late-stage of dry AMD known as geographic atrophy (GA), lacks effective treatment options. Genetic mouse models of AMD have revealed the significance of impaired lipid metabolism and anti-oxidative capacity in early/intermediate stage of AMD, but remains unclear in GA that severely damages visual function. Here, to investigate the potential relevance of peroxidized lipids in RPE for late-stage dry AMD, GPx4[fl/fl] mice underwent subretinal injections of RPE-specific AAV-Cre vector or control AAV vector. RPE-specific GPx4 deficiency led to rapid RPE degeneration resembling key features of late-stage dry AMD, including preceding loss of RPE cell polarity, accumulation of acrolein, malondialdehyde, and 4-hydroxynonenal, photoreceptor loss, lipofuscin-laden subretinal melanophage infiltration, and complement activation. Treatment with α-tocopherol and ferrostatin-1 mitigated RPE degeneration, and shrunk mitochondria were observed in GPx4 deficient mice, suggesting involvement of ferroptosis. Unexpectedly, necrostatin-1s, an inhibitor of necroptosis, also ameliorated RPE degeneration, and activation of RIP3 and MLKL along with inactivation of caspase-8 was observed, indicating crosstalk between ferroptosis and necroptosis pathways. Our findings shed light on the intricate mechanisms underlying RPE degeneration in AMD and highlight GPx4/lipid peroxidation as potential therapeutic targets. RPE-specific ablation of GPx4 in mice provides a valuable tool for further elucidating the interplay between lipid peroxidation, cell death pathways, and AMD pathogenesis, offering new insights for preclinical research and therapeutic development targeting GA.},
}
@article {pmid39426529,
year = {2025},
author = {Sadeghi, E and Valsecchi, N and Rahmanipour, E and Ejlalidiz, M and Hasan, N and Vupparaboina, KK and Ibrahim, MN and Rasheed, MA and Baek, J and Iannetta, D and Chhablani, J},
title = {Choroidal biomarkers in age-related macular degeneration.},
journal = {Survey of ophthalmology},
volume = {70},
number = {2},
pages = {167-183},
doi = {10.1016/j.survophthal.2024.10.004},
pmid = {39426529},
issn = {1879-3304},
mesh = {Humans ; *Choroid/pathology/metabolism/diagnostic imaging ; *Biomarkers/metabolism ; *Macular Degeneration/diagnosis/metabolism ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of central visual impairment in the elderly. The exact pathophysiological mechanisms for AMD remain uncertain. Several studies suggest that choroidal abnormalities and alterations are critical in AMD progression. The transition from manual to automated segmentation and binarization techniques has resulted in accurate and precise measurements of different choroidal parameters. These qualitative and quantitative parameters, known as choroidal imaging biomarkers, have advanced from basic vertical subfoveal choroidal thickness to more intricate 3-dimensional choroidal reconstruction methods in the last decade. Therefore, a comprehensive evaluation of choroidal metrics may investigate valuable insights into AMD, potentially guiding the future development of customized therapeutic strategies and personalized patient care in AMD management. We describe the role of different choroidal biomarkers in evaluating patients with AMD and their contribution to management.},
}
@article {pmid39424934,
year = {2024},
author = {Faghihi, S and Faghihi, H and Bazvand, F and Mehrabi Bahar, M and Torkashvand, A and Husein Ahmed, A and Rahimi, M and Akbarzadeh, A and Asadi Khameneh, E and Khalili Pour, E and Riazi-Esfahani, H},
title = {Baseline optical coherence tomography angiography biomarkers predict visual outcomes in treatment-naïve neovascular age-related macular degeneration patients.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {24528},
pmid = {39424934},
issn = {2045-2322},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Visual Acuity ; Retrospective Studies ; *Biomarkers ; Intravitreal Injections ; Macular Degeneration/drug therapy/diagnostic imaging ; Aged, 80 and over ; Treatment Outcome ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Fluorescein Angiography/methods ; Middle Aged ; },
abstract = {This retrospective study aimed to assess different macular neovascular network characteristics in relation to changes in best corrected visual acuity (BCVA) over 3 and 12 months following treatment. Using optical coherence tomography angiography, we reviewed the medical records of 46 treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept injections. The change in BCVA from baseline to 3 months and 12 months after treatment was recorded. The mean vessels percentage area, junctions density, lacunarity, and fractal dimension were significantly correlated with the change of BCVA from baseline to month 3 (P = 0.003, 0.046, 0.007, and 0.005 respectively). Fractal dimension and vessels percentage area were correlated with the change of BCVA from baseline to month 12 (P = 0.023 and 0.023 respectively). The findings suggest that baseline characteristics of macular neovascular complexes may serve as predictors for BCVA changes following treatment with aflibercept in nAMD patients.},
}
@article {pmid39424220,
year = {2024},
author = {Cai, J and Liao, F and Mao, Y and Liu, S and Wu, X and Tang, S and Wang, S and Shan, G and Wu, S},
title = {Regulation of LAMTOR1 by oxidative stress in retinal pigment epithelium: Implications for age-related macular degeneration pathogenesis.},
journal = {Experimental eye research},
volume = {249},
number = {},
pages = {110129},
doi = {10.1016/j.exer.2024.110129},
pmid = {39424220},
issn = {1096-0007},
mesh = {*Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Animals ; *Oxidative Stress/physiology ; *Macular Degeneration/metabolism/pathology/genetics ; Mice ; Humans ; *Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism/genetics ; Gene Expression Regulation ; RNA, Messenger/genetics ; Blotting, Western ; Autophagy/physiology ; Cells, Cultured ; Aldehydes/metabolism ; },
abstract = {Oxidative stress is a critical pathogenic factor for age-related macular degeneration (AMD). Autophagy serves as a mechanism to counteract oxidative stress. LAMTOR1 regulates mTORC1 activity by recruiting or disassembling it on the lysosome under the addition or deprivation of amino acids. This regulation inhibits or enhances autophagy. Our study investigates whether oxidative stress impacts LAMTOR1, thereby adapting to oxidative conditions. We employed oxidative stressors, menadione (VK3) and 4-hydroxynonenal (4-HNE), and observed a reduction of LAMTOR1 in both human and mouse retinal pigment epithelium (RPE) following short-term (1h) and prolonged exposures (24h). Nrf2 overexpression increased both lamtor1 mRNA and LAMTOR1 protein in the RPE. To determine if Nrf2 regulates lamtor1 transcription, we cloned the deletion mutants of the lamtor1 promoter into a luciferase reporter. Although the promoter contained antioxidant response elements, transcriptional activity depended on the interaction between Nrf2 and the constructs containing the transcriptional start site. Moreover, Nrf2-driven transcription was significantly reduced by an inhibitor of histone acetyltransferase, p300. Correspondingly, Nrf2 overexpression increased levels of acetylated histone 3 and p300. The reduction in LAMTOR1 by 4-HNE was reversed by pepstatin A and NH4Cl which block lysosomal degradation. 4-HNE increased TFEB nuclear translocation which was reversed by LAMTOR1 overexpression. In vivo, LAMTOR1 levels decreased in the photoreceptor and RPE layers of NaIO3-injected mice, compared to PBS-injected controls. In conclusion, oxidative injury reduces LAMTOR1, predominantly through lysosomal degradation although Nrf2-mediated histone acetylation enhances lamtor1 transcription. This study reveals a previously unrecognized regulatory mechanism of lamtor1 by oxidative stress, suggesting a novel role for LAMTOR1 in the pathogenesis of AMD.},
}
@article {pmid39424148,
year = {2025},
author = {Teo, ZL and Zhang, X and Yang, Y and Jin, L and Zhang, C and Poh, SSJ and Yu, W and Chen, Y and Jonas, JB and Wang, YX and Wu, WC and Lai, CC and Liu, Y and Goh, RSM and Ting, DSW},
title = {Privacy-Preserving Technology Using Federated Learning and Blockchain in Protecting against Adversarial Attacks for Retinal Imaging.},
journal = {Ophthalmology},
volume = {132},
number = {4},
pages = {484-494},
doi = {10.1016/j.ophtha.2024.10.017},
pmid = {39424148},
issn = {1549-4713},
mesh = {Humans ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; *Blockchain ; *Artificial Intelligence ; *Privacy ; *Macular Degeneration/diagnosis ; *Retina/diagnostic imaging ; *Computer Security ; Federated Learning ; },
abstract = {PURPOSE: Collaboration provides valuable data for robust artificial intelligence (AI) model development. Federated learning (FL) is a privacy-enhancing technology that allows collaboration while respecting privacy via the development of models without raw data transfer. However state-of-the-art FL models still face challenges in non-independent and identically distributed (non-IID) health care settings and remain susceptible to privacy breaches. We propose an FL framework coupled with blockchain technology to address these challenges.<br><br>DESIGN: Retrospective, multicohort study.<br><br>MAIN OUTCOME MEASURES: We evaluated our FL model performance in myopic macular degeneration (MMD) and OCT classification and compared our model against state-of the-art FL and centralized models.<br><br>METHODS: A total of 27 145 images from Singapore, China, and Taiwan were used to design a novel FL aggregation method for the detection of MMD from fundus photographs and macular disease from OCT scans in feature distribution skew and label distribution imbalance scenarios. We further performed adversarial attacks (label flipping and clean label). As proof of concept, blockchain was incorporated into FL to demonstrate secure transfer of model updates across collaborating sites.<br><br>RESULTS: Our FL model showed robust performance with an area under the curve (AUC) of 0.868 &#xb1; 0.009 for MMD detection and 0.970 &#xb1; 0.012 for OCT macular disease classification. In label flipping attack, our FL model had an AUC of 0.861 &#xb1; 0.019, similar to the centralized model (AUC 0.856 &#xb1; 0.015) and higher than other FL models (AUC 0.578-0.819). In clean label attack, our FL model had an AUC of 0.878 &#xb1; 0.006, which was comparable to the centralized model (AUC 0.878 &#xb1; 0.001) and superior to other state-of-the-art FL models with an AUC of 0.529 to 0.838. Simulation showed that the additional time with blockchain in 1 global epoch was approximately 5 seconds. The addition of blockchain to the FL framework was feasible with a minimal impact on model development time.<br><br>CONCLUSIONS: Our proposed FL algorithm overcomes the shortcoming of the traditional FL in non-IID situations and remains robust against adversarial attacks. The integration of blockchain adds further security during the transfer of model updates. Blockchain-enabled FL can be a trusted platform for collaborative health AI research.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid39419841,
year = {2025},
author = {Ogawa, M and Usui, Y and Tsubota, K and Goto, H},
title = {Association between axial length and uveitis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {3},
pages = {837-847},
pmid = {39419841},
issn = {1435-702X},
mesh = {Humans ; Male ; Female ; *Uveitis/diagnosis/physiopathology/complications/epidemiology/etiology ; Middle Aged ; *Axial Length, Eye/diagnostic imaging/pathology ; Adult ; Retrospective Studies ; Aged ; Risk Factors ; Young Adult ; *Myopia/diagnosis/complications/physiopathology ; },
abstract = {PURPOSE: Multiple studies have examined the association between myopia and various ocular diseases, but there is no clinical report of the relationship between myopia and uveitis. This study aimed to elucidate the relationship between myopia and uveitis by comparing axial lengths (AL) of uveitis patients with control individuals.<br><br>METHODS: This study included 1052 eyes (663 patients; 288 males, 375 females; median age 56.0&#xa0;years) with uveitis referred to Tokyo Medical University Hospital. Controls were 738 eyes with cataract but no other ocular diseases. AL was measured by IOLMaster or conventional A-mode ultrasound system. Uveitis eyes were grouped into various types of non-infectious uveitis, infectious uveitis, and unidentified uveitis. Median AL of each uveitis group was compared with control group using Mann-Whitney U-test, and also compared with adjustment for age and sex using multiple regression analysis. Binary logistic analysis was performed to examine whether AL plays a role in the risk of developing uveitis.<br><br>RESULTS: Of 1052 eyes, 808 eyes (76.8%) were diagnosed with non-infectious uveitis [sarcoidosis (176 eyes, 16.7%), Vogt-Koyanagi-Harada disease (122 eyes, 11.6%), Beh&#xe7;et's disease (130 eyes, 12.4%), and others (380 eyes, 36.1%)], 146 eyes (13.9%) with infectious uveitis, and 98 eyes (9.3%) with unidentified uveitis. Median AL in all uveitis eyes was significantly shorter than in control eyes (23.73 vs 24.31&#xa0;mm, p&#x2009;<&#x2009;0.001 unadjusted), and AL remained significantly shorter in uveitis than in control after age- and sex-adjustment (p&#x2009;<&#x2009;0.001). Median AL was significantly shorter in non-infectious uveitis (23.72&#xa0;mm) and in infectious uveitis (23.99&#xa0;mm) compared to controls (p&#x2009;<&#x2009;0.001 and&#x2009;<&#x2009;0.05, respectively), and was significantly shorter in non-infectious uveitis than in infectious uveitis (p&#x2009;<&#x2009;0.05). Each millimeter decrease in AL was associated with 1.266-fold increase in unadjusted risk [odds ratio (OR), 1.266; 95% confidence interval (CI), 1.196-1.341; p&#x2009;<&#x2009;0.001) and 1.446-fold in age- and sex-adjusted risk (OR, 1.446; 95% CI, 1.349-1.549; p&#x2009;<&#x2009;0.001) of developing uveitis.<br><br>CONCLUSION: Median AL of uveitis eyes with infectious or non-infectious etiologies was significantly shorter than that in control eyes, suggesting an increased risk of developing uveitis in eyes with shorter AL. This feature should be considered when exploring new pathogenetic mechanisms of uveitis.<br><br>KEY MESSAGES: What is known Shorter axial length may be associated with the pathogenesis of central serous chorioretinopathy and increased risk of early age-related macular degeneration. What is new Here we assessed the relationship between myopia and uveitis by comparing axial lengths of uveitis patients. Median axial length in all uveitis eyes was significantly shorter than in control eyes, and axial length remained significantly shorter in uveitis than in control after age- and sex-adjustment. Each millimeter decrease in axial length was associated with 1.266-fold increase in unadjusted risk and 1.446-fold in age- and sex-adjusted risk of developing uveitis.},
}
@article {pmid39419369,
year = {2024},
author = {Mullins, RF and Flamme-Wiese, MJ and Navratil, EM and Boese, EA and Varzavand, K and Riker, MJ and Wang, K and Stone, EM and Tucker, BA},
title = {Ghost vessels in the eye: Cell free choriocapillaris domains in atrophic age-related macular degeneration.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110128},
pmid = {39419369},
issn = {1096-0007},
support = {P30 EY025580/EY/NEI NIH HHS/United States ; R01 EY024605/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/blood supply/pathology ; Aged ; Male ; Female ; Aged, 80 and over ; *Retinal Pigment Epithelium/pathology ; *Geographic Atrophy/genetics ; Middle Aged ; Tissue Donors ; Capillaries/pathology ; Macular Degeneration/genetics/pathology/metabolism ; Genotype ; Complement Factor H/genetics ; },
abstract = {The choriocapillaris is a dense vascular bed in the inner choroid that supplies the photoreceptor cells and retinal pigment epithelium (RPE). While loss of choriocapillaris density has been described in association with age-related macular degeneration (AMD), whether these changes are primary or secondary to RPE degenerative changes in AMD has been debated. In this study we characterized choriocapillaris loss by quantifying "ghost" vessels in a series of 99 human donor maculae labeled with the UEA-I lectin, and found significant increases in early-intermediate AMD and a greater difference in geographic atrophy in areas with intact RPE. Eyes were genotyped at the CFH Tyr402His locus, and those homozygous for the His allele showed significantly more ghost vessels than those with other genotypes. When only non-AMD eyes were evaluated, His homozygotes had increased ghost vessel density but this trend did not reach statistical significance. These results support the notion that choriocapillaris death often precedes RPE degeneration in AMD and that this loss is an important therapeutic consideration for AMD.},
}
@article {pmid39418603,
year = {2024},
author = {Lewis, JS and Roskruge, M and Ah-Chan, J},
title = {Quantifying cost-savings in the treatment of neovascular age-related macular degeneration in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {137},
number = {1604},
pages = {35-41},
doi = {10.26635/6965.6533},
pmid = {39418603},
issn = {1175-8716},
mesh = {Humans ; New Zealand ; Retrospective Studies ; *Recombinant Fusion Proteins/therapeutic use/economics ; Male ; *Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Female ; Aged ; *Angiogenesis Inhibitors/economics/therapeutic use ; Cost Savings ; Macular Degeneration/drug therapy/economics ; Aged, 80 and over ; Cost-Benefit Analysis ; Wet Macular Degeneration/drug therapy/economics ; },
abstract = {AIMS: To estimate the cost-impact if faricimab were approved for the treatment of neovascular age-related macular degeneration (nAMD) in New Zealand.<br><br>METHODS: A retrospective, single-centre cost-analysis study. Data on intravitreal agent and injection intervals were obtained and statistically compared. Cost estimates were based on internal facility and publicly available data. The current costs of care were compared to two scenarios: one where all eyes receive faricimab, and another where eyes receiving aflibercept switch to faricimab.<br><br>RESULTS: A total of 352 eyes from 292 patients were analysed. Present values locally over 10 years were estimated at -$6,776,340 for the first scenario and $5,015,922 for the second, releasing 252 and 176 hours of clinical time per year, respectively. Nationally, the savings extrapolated to -$187,925,737 and $139,104,706, respectively. The analysis indicates significant direct cost savings for the health sector and potential reductions in patient harm due to fewer injections.<br><br>CONCLUSIONS: The approval of faricimab for the treatment of nAMD could result in substantial direct cost savings for the health sector. Additional benefits include reducing patient harm and improving ophthalmic health inequalities for M&#x101;ori and Pacific peoples. Further research in diverse patient populations across multiple centres is needed to estimate the magnitude of cost savings more accurately. This study highlights the potential of faricimab to alleviate the treatment burden and provide a more sustainable healthcare option for nAMD in New Zealand, especially in cases of recalcitrant nAMD, if used in a tailored and patient-specific manner alongside the existing armamentarium of treatments.},
}
@article {pmid39418083,
year = {2025},
author = {Conover, CA and Oxvig, C},
title = {The IGF System and Aging.},
journal = {Endocrine reviews},
volume = {46},
number = {2},
pages = {214-223},
pmid = {39418083},
issn = {1945-7189},
support = {//Mayo Clinic Research/ ; //Independent Research Fund Denmark/ ; },
mesh = {Humans ; *Aging/physiology/metabolism/genetics ; Animals ; Signal Transduction/physiology ; *Somatomedins/metabolism/physiology ; Cellular Senescence/physiology ; Alzheimer Disease/metabolism ; Mice ; },
abstract = {There is strong evidence that IGF signaling is involved in fundamental aspects of the aging process. However, the extracellular part of the IGF system is complex with various receptors, ligand effectors, high-affinity IGF-binding proteins, proteinases, and endogenous inhibitors that all, along with their biological context, must be considered. The IGF system components are evolutionarily conserved, underscoring the importance of understanding this system in physiology and pathophysiology. This review will briefly describe the different components of the IGF system and then discuss past and current literature regarding IGF and aging, with a focus on cellular senescence, model organisms of aging, centenarian genetics, and 3 age-related diseases-pulmonary fibrosis, Alzheimer disease, and macular degeneration-in appropriate murine models and in humans. Commonalities in mechanism suggest conditions where IGF system components may be disease drivers and potential targets in promoting healthy aging in humans.},
}
@article {pmid39418015,
year = {2024},
author = {Murphy, GSP and Saleh, A and Ayis, S and Cheema, MR and Mehta, A and Steel, DH and Membrey, L and Costen, M and Jackson, TL},
title = {Tissue Plasminogen Activator or Perfluoropropane for Submacular Hemorrhage in Age-Related Macular Degeneration: A Factorial Randomized Clinical Trial.},
journal = {JAMA ophthalmology},
volume = {142},
number = {12},
pages = {1157-1164},
pmid = {39418015},
issn = {2168-6173},
mesh = {Humans ; *Tissue Plasminogen Activator/administration &amp; dosage/therapeutic use ; Female ; *Fluorocarbons/administration &amp; dosage ; Male ; *Retinal Hemorrhage/drug therapy/physiopathology/diagnosis/etiology ; Double-Blind Method ; *Visual Acuity/physiology ; *Intravitreal Injections ; Aged ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Fibrinolytic Agents/therapeutic use/administration &amp; dosage ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Endotamponade ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Tomography, Optical Coherence ; Treatment Outcome ; Follow-Up Studies ; Fluorescein Angiography ; Feasibility Studies ; },
abstract = {IMPORTANCE: Evidence is limited to support therapies to treat submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD) as an adjunct to anti-vascular endothelial growth factor therapy (anti-VEGF).<br><br>OBJECTIVE: To determine if intravitreal tissue plasminogen activator (TPA) or gas improves visual acuity or promotes resolution of SMH secondary to neovascular AMD in eyes treated with ranibizumab.<br><br>This was a double-masked, sham-controlled, factorial randomized clinical trial and feasibility study that recruited participants from June 2014 to March 2019, with 12 months' follow-up. Included in the trial were patients from 4 UK vitreoretinal units who had fovea-involving SMH of at least 1 disc area secondary to neovascular AMD and were evaluated within 14 days of onset.<br><br>INTERVENTIONS: Study eyes received baseline ranibizumab and were then randomized 2:1:1:1 to 1 of 4 intravitreal treatments: sham injection, perfluoropropane (C3F8), TPA, or combined C3F8 and TPA (C3F8 + TPA). All eyes received monthly pro re nata ranibizumab therapy over 12 months. Outcome assessors were masked to intervention assignment.<br><br>MAIN OUTCOME AND MEASURE: Best-corrected visual acuity (BCVA) at month 3.<br><br>RESULTS: Fifty-three of 56 participants (95%; mean [SD] age, 81.5 [8.1] years; 33 female [59%]) reached the primary end point. Study eyes were randomized to the following intravitreal treatments: sham injection (n&#x2009;=&#x2009;23), C3F8 (n&#x2009;=&#x2009;11), TPA (n&#x2009;=&#x2009;11), or C3F8 + TPA (n&#x2009;=&#x2009;11). On factorial analysis, the combined TPA groups had significantly better month 3 mean logMAR BCVA than those not receiving TPA: 0.66 vs 0.98 (&#x3bc;d&#x2009;=&#x2009;-0.32; 95% CI, -0.58 to -0.07; P&#x2009;=&#x2009;.02). There was no statistically significant difference comparing groups that did vs did not receive C3F8: 0.80 vs 0.90 (&#x3bc;d&#x2009;=&#x2009;-0.11; 95% CI, -0.37 to 0.16; P&#x2009;=&#x2009;.43). The combined TPA groups were less likely to have SMH present at month 1 (10 of 18 [55.6%] vs 21 of 24 [87.5%]; P&#x2009;=&#x2009;.03), a benefit not evident in the combined gas groups. The mean logMAR BCVA at 3 months was not significantly different between the groups: monotherapy control, 0.99; C3F8, 0.97 (vs control &#x3bc;d&#x2009;=&#x2009;-0.02; 95% CI, -0.48 to 0.44); TPA, 0.70 (vs control &#x3bc;d&#x2009;=&#x2009;-0.29; 95% CI, -0.79 to 0.21); combined C3F8 and TPA, 0.71 (vs control &#x3bc;d&#x2009;=&#x2009;-0.36; 95% CI, -0.82 to 0.11); P&#x2009;=&#x2009;.11. No safety differences were identified across the treatment groups.<br><br>CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial suggest that TPA may increase the chance of visual acuity gain when added to ranibizumab therapy for neovascular AMD in eyes with SMH, warranting consideration of additional clinical trials.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01835067.},
}
@article {pmid39417312,
year = {2024},
author = {Kang, C and Lo, JE and Zhang, H and Ng, SM and Lin, JC and Scott, IU and Kalpathy-Cramer, J and Liu, SA and Greenberg, PB},
title = {Artificial intelligence for diagnosing exudative age-related macular degeneration.},
journal = {The Cochrane database of systematic reviews},
volume = {10},
number = {10},
pages = {CD015522},
pmid = {39417312},
issn = {1469-493X},
mesh = {Humans ; *Artificial Intelligence ; *Macular Degeneration/diagnosis ; *Sensitivity and Specificity ; Bias ; Tomography, Optical Coherence/methods ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a retinal disorder characterized by central retinal (macular) damage. Approximately 10% to 20% of non-exudative AMD cases progress to the exudative form, which may result in rapid deterioration of central vision. Individuals with exudative AMD (eAMD) need prompt consultation with retinal specialists to minimize the risk and extent of vision loss. Traditional methods of diagnosing ophthalmic disease rely on clinical evaluation and multiple imaging techniques, which can be resource-consuming. Tests leveraging artificial intelligence (AI) hold the promise of automatically identifying and categorizing pathological features, enabling the timely diagnosis and treatment of eAMD.<br><br>OBJECTIVES: To determine the diagnostic accuracy of artificial intelligence (AI) as a triaging tool for exudative age-related macular degeneration (eAMD).<br><br>SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three clinical trials registries, and Data Archiving and Networked Services (DANS) for gray literature. We did not restrict searches by language or publication date. The date of the last search was April 2024.<br><br>SELECTION CRITERIA: Included studies compared the test performance of algorithms with that of human readers to detect eAMD on retinal images collected from people with AMD who were evaluated at eye clinics in community or academic medical centers, and who were not receiving treatment for eAMD when the images were taken. We included algorithms that were either internally or externally validated or both.<br><br>DATA COLLECTION AND ANALYSIS: Pairs of review authors independently extracted data and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool with revised signaling questions. For studies that reported more than one set of performance results, we extracted only one set of diagnostic accuracy data per study based on the last development stage or the optimal algorithm as indicated by the study authors. For two-class algorithms, we collected data from the 2x2 table whenever feasible. For multi-class algorithms, we first consolidated data from all classes other than eAMD before constructing the corresponding 2x2 tables. Assuming a common positivity threshold applied by the included studies, we chose random-effects, bivariate logistic models to estimate summary sensitivity and specificity as the primary performance metrics.<br><br>MAIN RESULTS: We identified 36 eligible studies that reported 40 sets of algorithm performance data, encompassing over 16,000 participants and 62,000 images. We included 28 studies (78%) that reported 31 algorithms with performance data in the meta-analysis. The remaining nine studies (25%) reported eight algorithms that lacked usable performance data; we reported them in the qualitative synthesis. Study characteristics and risk of bias Most studies were conducted in Asia, followed by Europe, the USA, and collaborative efforts spanning multiple countries. Most studies identified study participants from the hospital setting, while others used retinal images from public repositories; a few studies did not specify image sources. Based on four of the 36 studies reporting demographic information, the age of the study participants ranged from 62 to 82 years. The included algorithms used various retinal image types as model input, such as optical coherence tomography (OCT) images (N = 15), fundus images (N = 6), and multi-modal imaging (N = 7). The predominant core method used was deep neural networks. All studies that reported externally validated algorithms were at high risk of bias mainly due to potential selection bias from either a two-gate design or the inappropriate exclusion of potentially eligible retinal images (or participants). Findings Only three of the 40 included algorithms were externally validated (7.5%, 3/40). The summary sensitivity and specificity were 0.94 (95% confidence interval (CI) 0.90 to 0.97) and 0.99 (95% CI 0.76 to 1.00), respectively, when compared to human graders (3 studies; 27,872 images; low-certainty evidence). The prevalence of images with eAMD ranged from 0.3% to 49%. Twenty-eight algorithms were reportedly either internally validated (20%, 8/40) or tested on a development set (50%, 20/40); the pooled sensitivity and specificity were 0.93 (95% CI 0.89 to 0.96) and 0.96 (95% CI 0.94 to 0.98), respectively, when compared to human graders (28 studies; 33,409 images; low-certainty evidence). We did not identify significant sources of heterogeneity among these 28 algorithms. Although algorithms using OCT images appeared more homogeneous and had the highest summary specificity (0.97, 95% CI 0.93 to 0.98), they were not superior to algorithms using fundus images alone (0.94, 95% CI 0.89 to 0.97) or multimodal imaging (0.96, 95% CI 0.88 to 0.99; P for meta-regression = 0.239). The median prevalence of images with eAMD was 30% (interquartile range [IQR] 22% to 39%). We did not include eight studies that described nine algorithms (one study reported two sets of algorithm results) to distinguish eAMD from normal images, images of other AMD, or other non-AMD retinal lesions in the meta-analysis. Five of these algorithms were generally based on smaller datasets (range 21 to 218 participants per study) yet with a higher prevalence of eAMD images (range 33% to 66%). Relative to human graders, the reported sensitivity in these studies ranged from 0.95 and 0.97, while the specificity ranged from 0.94 to 0.99. Similarly, using small datasets (range 46 to 106), an additional four algorithms for detecting eAMD from other retinal lesions showed high sensitivity (range 0.96 to 1.00) and specificity (range 0.77 to 1.00).<br><br>AUTHORS' CONCLUSIONS: Low- to very low-certainty evidence suggests that an algorithm-based test may correctly identify most individuals with eAMD without increasing unnecessary referrals (false positives) in either the primary or the specialty care settings. There were significant concerns for applying the review findings due to variations in the eAMD prevalence in the included studies. In addition, among the included algorithm-based tests, diagnostic accuracy estimates were at risk of bias due to study participants not reflecting real-world characteristics, inadequate model validation, and the likelihood of selective results reporting. Limited quality and quantity of externally validated algorithms highlighted the need for high-certainty evidence. This evidence will require a standardized definition for eAMD on different imaging modalities and external validation of the algorithm to assess generalizability.},
}
@article {pmid39415143,
year = {2024},
author = {Jang, W and Choi, J and Kim, H},
title = {Associations of mediterranean diet score and age-related macular degeneration in Korean elderly.},
journal = {BMC public health},
volume = {24},
number = {1},
pages = {2846},
pmid = {39415143},
issn = {1471-2458},
mesh = {Humans ; Male ; Female ; *Macular Degeneration/epidemiology ; Republic of Korea/epidemiology ; Aged ; Cross-Sectional Studies ; *Diet, Mediterranean/statistics &amp; numerical data ; *Nutrition Surveys ; Aged, 80 and over ; Risk Factors ; },
abstract = {BACKGROUND: Previous studies have reported associations between individual nutrients or specific foods and the risk of age-related macular degeneration (AMD). However, the relationship between overall dietary quality, specifically the alternative Mediterranean diet (aMED) score, and AMD remains unclear. Therefore, this study aimed to investigate the association between the aMED score, as an indicator of overall diet quality, and AMD in the Korean population.<br><br>METHODS: We conducted a cross-sectional analysis using nationally representative samples of older adults aged&#x2009;&#x2265;&#x2009;65 years (895 men and 1,191 women) from the Korea National Health and Nutrition Examination Survey (2017-2018). Food intake and the aMED score were estimated using 24-h recall. AMD was diagnosed by an ophthalmologist based on fundus photography. The associations of aMED score tertiles with AMD were determined using odds ratios (ORs) from multivariate logistic regressions.<br><br>RESULTS: Multiple logistic regression analysis revealed a significantly negative association between the aMED score and AMD (adjusted ORs&#x2009;=&#x2009;0.58; 95% confidence interval&#x2009;=&#x2009;0.39-0.88; p-trend&#x2009;=&#x2009;0.021) in older men after adjusting for confounding factors such as age, body mass index, family monthly income, current smoking, alcohol consumption, physical activity, chronic disease status, and energy intake. Notably, this association was exclusively observed in men, and no significant association was observed between the aMED score and AMD in women (adjusted OR&#x2009;=&#x2009;0.88; 95% CI&#x2009;=&#x2009;0.61-1.29; p-trend&#x2009;=&#x2009;0.691).<br><br>CONCLUSIONS: This study's findings suggest that a high aMED score may be associated with a reduced risk of AMD in older men. Future studies with larger sample sizes and a prospective or interventional design are required to enhance current understanding regarding the association between diet quality and AMD.},
}
@article {pmid39413870,
year = {2025},
author = {Phu, J and Khuu, SK and Nivison-Smith, L and Kalloniatis, M},
title = {Standard automated perimetry for glaucoma and diseases of the retina and visual pathways: Current and future perspectives.},
journal = {Progress in retinal and eye research},
volume = {104},
number = {},
pages = {101307},
doi = {10.1016/j.preteyeres.2024.101307},
pmid = {39413870},
issn = {1873-1635},
mesh = {Humans ; *Glaucoma/physiopathology/diagnosis ; *Retinal Diseases/physiopathology/diagnosis ; *Visual Field Tests/methods/standards ; Visual Fields/physiology ; *Visual Pathways/physiopathology/physiology ; Automation ; },
abstract = {Static automated perimetry (SAP) remains a mainstay of functional assessment of the visual field in diseases of the visual pathway, such as glaucoma and age-related macular degeneration. The fundamental psychophysical task of responding to stimuli of different levels of contrast has remained minimally changed since its inception in the 1980s, and this is potentially the root of several unresolved issues involving the technique. Enduring issues include the optimisation of SAP parameters for maximising defect detection, the influence of subjective behaviour on the response, structure-function discordance, and ageing- and disease-related changes of the visual pathway. Addressing these issues has been a focus of our research program and is the subject of this manuscript. We will review some of the basic psychophysical principles and methods that have contributed to the development of SAP and their contributions to its output measurements. Parameters that are interrogated include stimulus size and background luminance and their modification to improve defect defection in glaucoma and age-related macular degeneration. We propose frameworks for optimising testing parameters and leveraging the results for changing clinical care. In our pursuit of optimising the structure-function relationship in the eye, several areas of research have been developed and explored, including: the reconciliation of subjective responses in perimetry; by minimising sources of biases, such as Method of Limits we have been able to equate static and kinetic perimetry outputs in relation to underlying structural loci. This also formed the basis for our clustering framework, which groups together statistically similar structural and functional test locations to maximise structure-function concordance. Throughout the manuscript, we review the scientific underpinnings of clinical measurements, framing application into real-world patients to improve clinical practice.},
}
@article {pmid39412071,
year = {2024},
author = {Ghosh, S and Hose, S and Sinha, D},
title = {AKT2-mediated lysosomal dysfunction promotes secretory autophagy in retinal pigment epithelium (RPE) cells.},
journal = {Autophagy},
volume = {20},
number = {12},
pages = {2841-2842},
pmid = {39412071},
issn = {1554-8635},
support = {K99 EY033421/EY/NEI NIH HHS/United States ; R01 EY031594/EY/NEI NIH HHS/United States ; R01 EY032516/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology ; *Autophagy/physiology ; Humans ; *Lysosomes/metabolism ; *Macular Degeneration/metabolism/pathology ; *Proto-Oncogene Proteins c-akt/metabolism ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with the non-neovascular or atrophic form being the most common. Current treatment options are limited, emphasizing the urgent need for new therapeutic strategies. Our key finding is that increased levels of AKT2 in the RPE cells impair lysosomal function and trigger secretory autophagy; a non-canonical macroautophagy/autophagy pathway where cellular materials are released via the plasma membrane rather than being degraded by lysosomes. We showed that this process involves a protein complex, AKT2-SYTL1-TRIM16-SNAP23, releasing factors contributing to drusen biogenesis, a clinical hallmark of AMD development. Importantly, SIRT5 can inhibit this pathway, potentially offering a protective effect. Understanding mechanisms by which this non-canonical autophagy pathway promotes extracellular waste accumulation could provide new insights into drusen biogenesis. Future therapies for atrophic AMD could focus on regulating secretory autophagy or manipulating proteins involved in this process.},
}
@article {pmid39410789,
year = {2025},
author = {Santamaría, J and Pagani, F and Monés, J},
title = {Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy?.},
journal = {European journal of ophthalmology},
volume = {35},
number = {1},
pages = {NP41-NP45},
doi = {10.1177/11206721241290263},
pmid = {39410789},
issn = {1724-6016},
mesh = {Humans ; Female ; *Retinal Pigment Epithelium/pathology ; *Geographic Atrophy/diagnosis ; Aged, 80 and over ; *Tomography, Optical Coherence ; *Visual Acuity ; *Fluorescein Angiography ; Atrophy ; Disease Progression ; },
abstract = {Geographic atrophy (GA), a late manifestation of age-related macular degeneration (AMD), leads to irreversible vision loss. Early identification of precursor lesions, such as incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA), is crucial for predicting GA formation. The latter stage has been associated with irreversible and progressive changes, and the eventual development of a dense scotoma on the compromised area. We present an 80-year-old woman with AMD in both eyes, demonstrating progressive changes over a 2-year follow-up. While the right eye developed cRORA with vision decline, the left eye exhibited unexpected restoration of the outer retinal layers within the cRORA lesion. This finding challenges the notion of "end-stage atrophy" in GA development and highlights the potential reversibility of early atrophic lesions. Recognizing these dynamics has implications for the development of targeted therapies aimed at preserving vision in AMD's early stages.},
}
@article {pmid39409079,
year = {2024},
author = {Cerecedo-Zapata, CM and Tapia-Guerrero, YS and Ramírez-González, JA and Meza-Dorantes, A and Tercero-Pérez, KN and Cortés, H and Guerra-Grajeda, A and Ortega-Ibarra, IH and Gatica-Ramos, G and Poblete-Velazquez, A and Leyva-García, N and Velázquez-Pérez, L and Cisneros, B and Magaña, JJ},
title = {Current Overview of Spinocerebellar Ataxia Type 7 in Mexican Population: Challenges in Specialized Care for a Rare Disease.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
pmid = {39409079},
issn = {1422-0067},
mesh = {Humans ; Age of Onset ; Haplotypes ; Mexico/epidemiology ; Phenotype ; *Rare Diseases/genetics/therapy/diagnosis/epidemiology ; *Spinocerebellar Ataxias/genetics/epidemiology/therapy/diagnosis ; Trinucleotide Repeat Expansion ; },
abstract = {Spinocerebellar ataxia type 7 (SCA7) is a rare genetic disease characterized by progressive cerebellar syndrome and macular degeneration. In a previous study, we clinically and genetically characterized a group of Mexican patients, which represented one of the largest cohorts of SCA7 patients worldwide and demonstrated that all patients had a unique genetic origin. Our laboratory developed a program for the diagnosis, medical care, and long-term follow-up of these patients living in Veracruz State, and in this report, we present an update to this research, covering 2013 to 2024. So far, we identified 172 SCA7 carriers, with a few cases outside Veracruz, and our data support that the length of the CAG repeat tract mainly determines disease severity and life expectancy, and accordingly, we define three different phenotypes, early-onset (EO), classical-onset (CO), and late-onset (LO), with EO patients showing the lowest life expectancy. Furthermore, we found that parental transmission of mutant alleles leads to increased CAG repeat instability, compared to maternal ones. Interestingly, a haplotype analysis revealed that patients outside Veracruz may have different genetic origins. In conclusion, longitudinal observations of SCA7 patients provide insight into the natural history of SCA7 and help to design strategies for diagnosis, genetic counseling, physical rehabilitation, and therapeutic alternatives.},
}
@article {pmid39408817,
year = {2024},
author = {Oshitari, T},
title = {Translational Research and Therapies for Neuroprotection and Regeneration of the Optic Nerve and Retina: A Narrative Review.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
pmid = {39408817},
issn = {1422-0067},
support = {22K09829//a grant-in-aid from the Ministry of Education, Science, Sports, and Culture of the Japanese Gov-ernment/ ; N/A//the grant-in-aid from the Eye Research Foundation for the Aged in Japan/ ; },
mesh = {Humans ; *Translational Research, Biomedical ; *Optic Nerve ; Animals ; *Neuroprotection ; *Retina ; Neuroprotective Agents/therapeutic use ; Nerve Regeneration ; Optic Nerve Diseases/therapy ; Retinal Diseases/therapy ; },
abstract = {Most retinal and optic nerve diseases pose significant threats to vision, primarily due to irreversible retinal neuronal cell death, a permanent change, which is a critical factor in their pathogenesis. Conditions such as glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration are the top four leading causes of blindness among the elderly in Japan. While standard treatments-including reduction in intraocular pressure, anti-vascular endothelial growth factor therapies, and retinal photocoagulation-can partially delay disease progression, their therapeutic effects remain limited. To address these shortcomings, a range of neuroprotective and regenerative therapies, aimed at preventing retinal neuronal cell loss, have been extensively studied and increasingly integrated into clinical practice over the last two decades. Several of these neuroprotective therapies have achieved on-label usage worldwide. This narrative review introduces several neuroprotective and regenerative therapies for retinal and optic nerve diseases that have been successfully translated into clinical practice, providing foundational knowledge and success stories that serve as valuable references for researchers in the field.},
}
@article {pmid39408582,
year = {2024},
author = {Sheibani, N and Song, YS and Farnoodian, M and Inampudi, S and Hanna, B and Wang, S and Darjatmoko, SR and Sorenson, CM},
title = {Bim Expression Influences Choroidal Endothelial Cell Characteristics and Their Response to Therapeutic Intervention.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
pmid = {39408582},
issn = {1422-0067},
support = {Research Support for Macular Degeneration//Carl Marshall Reeves &amp; Mildred Reeves Foundation/ ; P30 EY016665/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; P30 EY016665, EY034646, EY030076/EY/NEI NIH HHS/United States ; Endoument Found//Retina Research Foundation/ ; R01 EY030076/EY/NEI NIH HHS/United States ; Unrestricted Award to the Department of Ophthalmology and Visual Sciences//Research to Prevent Blindness/ ; AMD Innovation Fund//Pat and Jay Smith/ ; R21 EY034646/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Bcl-2-Like Protein 11/metabolism/genetics ; *Endothelial Cells/metabolism ; Mice ; *Choroid/metabolism ; *Choroidal Neovascularization/metabolism/pathology/genetics ; Vascular Endothelial Growth Factor A/metabolism/genetics ; Mice, Knockout ; Apoptosis ; Mice, Inbred C57BL ; Cell Proliferation ; Propranolol/pharmacology ; },
abstract = {In the aging population, choroidal vessels grow through the Bruch's membrane, resulting in a loss of central vision due to choroidal neovascularization (CNV). During active neovascularization, CNV is associated with inappropriate levels of apoptosis in multiple cell types, including choroidal endothelial cells (ChECs). Bim is a pro-apoptotic member of the Bcl-2 family. It is essential for cell apoptosis due to exposure to drugs such as dexamethasone or decreased pro-survival factors, including vascular endothelial growth factor (VEGF). To better elucidate the cell autonomous contribution of Bim expression in the integrity and neovascularization of the choroidal vasculature, we isolated ChECs from wild-type and Bim-deficient (Bim[-/-]) mice. ChECs lacking Bim expression demonstrated increased expression of VEGF, osteopontin, and the inflammatory cytokines Rantes/Ccl5 and IL6. Bim[-/-] ChECs were more proliferative and demonstrated an increased capacity to undergo capillary morphogenesis. Anti-VEGF had a diminished capacity to disrupt capillary morphogenesis in Bim[-/-] ChECs. In vivo, utilizing the mouse laser photocoagulation model, anti-VEGF treatment mitigated CNV in wild-type but not Bim[-/-] mice. We also tested other modalities that are thought to not require the intrinsic death pathway for their function and showed that propranolol, anti-CTGF, and the TSP1-mimetic peptide ABT898 mitigated CNV in mice lacking Bim expression to varying degrees. Thus, in ChECs, Bim expression could impact the effectiveness of treatment modalities that require the intrinsic death pathway to mitigate CNV.},
}
@article {pmid39408566,
year = {2024},
author = {Mo, Q and Liu, X and Gong, W and Wang, Y and Yuan, Z and Sun, X and Wang, S},
title = {Pinpointing Novel Plasma and Brain Proteins for Common Ocular Diseases: A Comprehensive Cross-Omics Integration Analysis.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
pmid = {39408566},
issn = {1422-0067},
support = {82173624//National Natural Science Foundation of China/ ; 82373686//National Natural Science Foundation of China/ ; ZR2019ZD02//Natural Science Foundation of Shandong Province/ ; tsqn202211025//Taishan Scholar Project of Shandong Province/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; *Quantitative Trait Loci ; *Eye Diseases/genetics/metabolism/blood ; *Brain/metabolism ; Blood Proteins/genetics/metabolism ; Genetic Predisposition to Disease ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Proteome/metabolism ; },
abstract = {The pathogenesis of ocular diseases (ODs) remains unclear, although genome-wide association studies (GWAS) have identified numerous associated genetic risk loci. We integrated protein quantitative trait loci (pQTL) datasets and five large-scale GWAS summary statistics of ODs under a cutting-edge systematic analytic framework. Proteome-wide association studies (PWAS) identified plasma and brain proteins associated with ODs, and 11 plasma proteins were identified by Mendelian randomization (MR) and colocalization (COLOC) analyses as being potentially causally associated with ODs. Five of these proteins (protein-coding genes ECI1, LCT, and NPTXR for glaucoma, WARS1 for age-related macular degeneration (AMD), and SIGLEC14 for diabetic retinopathy (DR)) are newly reported. Twenty brain-protein-OD pairs were identified by COLOC analysis. Eight pairs (protein-coding genes TOM1L2, MXRA7, RHPN2, and HINT1 for senile cataract, WARS1 and TDRD7 for AMD, STAT6 for myopia, and TPPP3 for DR) are newly reported in this study. Phenotype-disease mapping analysis revealed 10 genes related to the eye/vision phenotype or ODs. Combined with a drug exploration analysis, we found that the drugs related to C3 and TXN have been used for the treatment of ODs, and another eight genes (GSTM3 for senile cataract, IGFBP7 and CFHR1 for AMD, PTPMT1 for glaucoma, EFEMP1 and ACP1 for myopia, SIRPG and CTSH for DR) are promising targets for pharmacological interventions. Our study highlights the role played by proteins in ODs, in which brain proteins were taken into account due to the deepening of eye-brain connection studies. The potential pathogenic proteins finally identified provide a more reliable reference range for subsequent medical studies.},
}
@article {pmid39408240,
year = {2024},
author = {Masri, A and Armanazi, M and Inouye, K and Geierhart, DL and Davey, PG and Vasudevan, B},
title = {Macular Pigment Optical Density as a Measurable Modifiable Clinical Biomarker.},
journal = {Nutrients},
volume = {16},
number = {19},
pages = {},
pmid = {39408240},
issn = {2072-6643},
mesh = {Humans ; *Macular Pigment/metabolism ; *Biomarkers ; *Macular Degeneration ; Macula Lutea/metabolism ; Carotenoids/metabolism ; Oxidative Stress ; Antioxidants ; Visual Acuity ; Diabetic Retinopathy ; Dietary Supplements ; },
abstract = {BACKGROUND: Carotenoids are present throughout retina and body its dense deposition leads to an identifiable yellow spot in the macula. Macular pigment optical density (MPOD) measured in the macula is vital to macular well-being and high-resolution visual acuity. MPOD has also been associated with various health and disease states. We sought to review the literature on this topic and summarize MPODs role as a measurable modifiable clinical biomarker, particularly as a measure of the eye's antioxidant capacity in the context of oxidative damage and retinal ischemia.<br><br>METHODS: A literature review collated the articles relevant to MPOD, carotenoid intake or supplementation, and their influence on various health and disease states.<br><br>RESULTS: Literature reveals that MPOD can serve as a reliable biomarker for assessing the retinal defense mechanisms against oxidative stress and the deleterious effects of excessive light exposure. Elevated MPOD levels offer robust protection against the onset and progression of age-related macular degeneration (AMD), a prevalent cause of vision impairment among the elderly population. MPOD's implications in diverse ocular conditions, including diabetic retinopathy and glaucoma, have been explored, underscoring the real need for clinical measurement of MPOD. The integration of MPOD measurement into routine eye examinations presents an unparalleled opportunity for early disease detection, precise treatment planning, and longitudinal disease monitoring.<br><br>CONCLUSIONS: Longitudinal investigations underscore the significance of MPOD in the context of age-related ocular diseases. These studies show promise and elucidate the dynamic nuances of MPOD's status and importance as a measurable, modifiable clinical biomarker.},
}
@article {pmid39408001,
year = {2024},
author = {Dimalanta, L and Pithadia, K and Shenkute, NT and Strelow, B and Zhang, Z and Ulrich, J and Zhang, AY and Fleischman, D},
title = {Disease Associations among Patients Afflicted with Both Glaucoma and Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {19},
pages = {},
pmid = {39408001},
issn = {2077-0383},
support = {T35 AG038047/AG/NIA NIH HHS/United States ; NIA 2-T35-AG038047/AG/NIA NIH HHS/United States ; },
abstract = {Background/Objectives: This study investigates whether there is an increased propensity to systemic conditions in patients with both age-related macular degeneration (AMD) and glaucoma in order to provide greater insight into patients' overall health and response to physiologic stress. Methods: A large retrospective dataset review was conducted between April 2004 and June 2018, distinguishing four groups based on international classification of diseases (ICD) codes: glaucoma only, AMD only, glaucoma and AMD, and cataracts only (as an age-matched control). The systemic disease prevalence of each group was calculated, and a Friedman analysis was used to compare the prevalence between the groups. Results: This study identified 5243 patients with glaucoma only, 6726 with AMD only, 402 with combined disease, and 25,450 with cataracts only. Age and racial distributions varied between groups in a predictable manner. Two conditions, heart failure (HF) and dementia, had a statistically higher prevalence in patients with both glaucoma and AMD compared to those with glaucoma alone (HF p = 0.036, dementia p = 0.024) and cataracts alone (HF p = 0.003, dementia p = 0.036). There was no significant difference observed in terms of ethnicity and gender among the different disease groups (p > 0.05). Conclusions: Both AMD and glaucoma individually portend a higher rate of comorbidities than age-matched controls. Patients with concomitant AMD and glaucoma demonstrate a uniquely higher prevalence of heart failure and dementia than those with either disease alone. The underlying association and pathologic mechanisms warrant further investigation to improve the overall health management and prognostication for these individuals.},
}
@article {pmid39407875,
year = {2024},
author = {Henriques, C and da Ana, R and Krambeck, K and Miguel, S and Santini, A and Zielińska, A and Souto, EB},
title = {Monoclonal Antibodies for the Treatment of Ocular Diseases.},
journal = {Journal of clinical medicine},
volume = {13},
number = {19},
pages = {},
pmid = {39407875},
issn = {2077-0383},
abstract = {Monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy, offering unprecedented specificity and diverse mechanisms to combat malignant cells. These biologic agents have emerged as a cornerstone in targeted cancer treatment, binding to specific antigens on cancer cells and exerting their therapeutic effects through various mechanisms, including inhibition of signaling pathways, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). The unique ability of mAbs to engage the immune system and directly interfere with cancer cell function has significantly enhanced the therapeutic armamentarium against a broad spectrum of malignancies. mAbs were initially studied in oncology; however, today, treatments have been developed for eye diseases. This review discusses the current applications of mAbs for the treatment of ocular diseases, discussing the specificity and the variety of mechanisms by which these molecules exhibit their therapeutic effects. The benefits, drawbacks, effectiveness, and risks associated with using mAbs in ophthalmology are highlighted, focusing on the most relevant ocular diseases and mAbs currently in use. Technological advances have led to in vitro production methods and recombinant engineering techniques, allowing the development of chimeric, humanized, and fully human mAbs. Nowadays, many humanized mAbs have several applications, e.g., for the treatment of age-related macular disease, diabetic retinopathy, and uveitis, while studies about new applications of mAbs, such as for SARS-CoV-2 infection, are also currently ongoing to seek more efficient and safe approaches to treat this new ocular disease.},
}
@article {pmid39407140,
year = {2024},
author = {Bilici, S and Selçuk, N and Küçük, N and Uğurbaş, SH},
title = {Serial intravitreal injections in age-related macular degeneration patients from the dry eye disease perspective: a cross-sectional study.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {453},
pmid = {39407140},
issn = {1471-2415},
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; *Intravitreal Injections ; Middle Aged ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Dry Eye Syndromes/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Wet Macular Degeneration/drug therapy/diagnosis ; Ranibizumab/administration &amp; dosage ; Meibomian Glands/drug effects/pathology/diagnostic imaging ; Tears/metabolism ; Bevacizumab/administration &amp; dosage/therapeutic use ; },
abstract = {BACKGROUND: To evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI.<br><br>RESULTS: Forty-two nAMD patients with a mean age of 63.3&#x2009;&#xb1;&#x2009;19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6-22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p&#x2009;=&#x2009;0.872), avgNITBUT (6.2 vs. 7.2, p&#x2009;=&#x2009;0.968), Shirmer-1 results (7 vs. 7, p&#x2009;=&#x2009;0.854), corneal staining (0.3 vs. 0.2, p&#x2009;=&#x2009;0.341), lower and upper MG loss rate (29.3 vs. 28.4, p&#x2009;=&#x2009;0.162, and 27.1 vs. 26.9, p&#x2009;=&#x2009;0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p&#x2009;=&#x2009;0.042, and r:0.365, p&#x2009;=&#x2009;0.047).<br><br>CONCLUSION: The results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements.},
}
@article {pmid39406933,
year = {2025},
author = {Yu, S and Jones, IL and Maunz, A and Bachmeier, I and Albrecht, T and Ebneter, A and Gliem, M and Staurenghi, G and Sadda, SR and Chakravarty, U and Fauser, S},
title = {Artificial intelligence-based analysis of retinal fluid volume dynamics in neovascular age-related macular degeneration and association with vision and atrophy.},
journal = {Eye (London, England)},
volume = {39},
number = {1},
pages = {154-161},
pmid = {39406933},
issn = {1476-5454},
mesh = {Humans ; *Visual Acuity/physiology ; *Subretinal Fluid/diagnostic imaging ; Female ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Tomography, Optical Coherence/methods ; Aged ; Male ; Angiogenesis Inhibitors/therapeutic use ; *Artificial Intelligence ; Atrophy ; Intravitreal Injections ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Ranibizumab/therapeutic use ; *Retina/pathology ; },
abstract = {BACKGROUND/OBJECTIVES: To characterise morphological changes in neovascular age-related macular degeneration (nAMD) during anti-angiogenic therapy and explore relationships with best-corrected visual acuity (BCVA) and development of macular atrophy (MA).<br><br>SUBJECTS/METHODS: Post-hoc analysis of the phase III HARBOR trial. SD-OCT scans from 1097 treatment-na&#xef;ve nAMD eyes were analysed. Volumes of intraretinal cystoid fluid (ICF), subretinal hyperreflective material (SHRM), subretinal fluid (SRF), pigment epithelial detachment (PED) and cyst-free retinal volume (CFRV) were measured by deep-learning model. Volumes were analysed by treatment regimen, macular neovascularisation (MNV) subtypes and topographic location. Associations of volumetric features with BCVA and MA development were quantified at month 12/24.<br><br>RESULTS: Differences in feature volume changes by treatment regimens and MNV subtypes were observed. Each additional 100 nanolitre unit (AHNU) of residual ICF, SHRM and CFRV at month 1 in the fovea was associated with deficits of 10.3, 7.3 and 12.2 letters at month 12. Baseline AHNUs of ICF, CFRV and PED were associated with increased odds of MA development at month 12 by 10%, 4% and 3%. While that of SRF was associated with a decrease in odds of 5%. Associations at month 24 were similar to those at month 12.<br><br>CONCLUSION: Eyes with different MNV subtypes showed distinct trajectories of feature volume response to treatment. Higher baseline volumes of ICF or PED and lower baseline volume of SRF were associated with higher likelihoods of MA development over 24 months. Residual intraretinal fluid, including ICF and CFRV, along with SHRM were predictors of poor visual outcomes.},
}
@article {pmid39406463,
year = {2025},
author = {Chen, SY and Xu, YM and Tam, POS and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association of polymorphisms in the HTRA1 gene with myopia.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {4},
pages = {456-462},
doi = {10.1136/bjo-2024-325935},
pmid = {39406463},
issn = {1468-2079},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Genotyping Techniques ; Haplotypes ; *High-Temperature Requirement A Serine Peptidase 1/genetics ; Hong Kong/epidemiology ; *Myopia/genetics ; *Polymorphism, Single Nucleotide ; East Asian People/genetics ; },
abstract = {PURPOSE: To evaluate the associations of single-nucleotide polymorphisms (SNPs) in the high-temperature requirement protease A 1 (HTRA1) gene with myopia.<br><br>METHODS: 25 SNPs in HTRA1 were selected, including 23 haplotype-tagging SNPs, SNP rs2142308 from a previous genome-wide association study (GWAS) of myopia and rs11200638, a SNP strongly associated with age-related macular degeneration (AMD). All SNPs were genotyped in a Hong Kong Chinese cohort of 533 myopia subjects (including 175 high myopia, 189 moderate myopia and 189 mild myopia) and 280 non-myopic controls. The association of individual SNPs were evaluated in overall myopia and different subgroups of myopia using logistic regression.<br><br>RESULTS: A tagging SNP, rs11200647, was significantly associated with myopia (p=2.17&#xd7;10[-4], OR=0.67). Nominal associations were detected for the AMD-associated SNP rs11200638 (p=0.0042, OR=1.37) and tagging SNPs rs12266322 (p=0.0048, OR=0.59) and rs17103569 (p=0.047, OR=1.34). The association of rs11200647 with myopia remained significant after adjusting for rs11200638, rs12266322 and rs17103569. In sub-group analysis, two tagging SNPs, rs11200647 (p=2.24&#xd7;10[-4], OR=0.58) and rs12266322 (p=8.31&#xd7;10[-4], OR=0.39), showed significant association with moderate myopia. In haplotype association analysis, haplotypes AT (p=1.00&#xd7;10[-4], OR=1.77) and haplotype GT (p=0.0019, OR=0.64), defined by rs11200647 and rs66884382, were significantly associated with myopia.<br><br>CONCLUSIONS: This study provided new evidence to support HTRA1 as an associated gene for myopia, especially moderate myopia. The findings suggested that myopia and AMD may have shared genetic components.},
}
@article {pmid39406195,
year = {2024},
author = {Guo, Y and Xu, N and Yan, H and Li, J and Huang, L and Zhu, L and Du, W and Liu, Z and Zhao, M},
title = {Splice Variant of Retinal G-Protein-Coupled Receptor Deletion-Mediated Dysregulation of Autophagy Increases the Susceptibility to Age-Related Macular Degeneration-Like Defects.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {611-624},
doi = {10.1159/000541991},
pmid = {39406195},
issn = {1423-0259},
mesh = {Animals ; *Autophagy/physiology ; Mice ; *Disease Models, Animal ; *Electroretinography ; Receptors, G-Protein-Coupled/genetics/metabolism ; Mice, Inbred C57BL ; Macular Degeneration/genetics/metabolism/physiopathology/pathology ; Retinal Pigment Epithelium/metabolism/pathology ; Retina/metabolism/physiopathology/pathology ; Humans ; Microscopy, Electron, Transmission ; Blotting, Western ; Fluorescein Angiography ; },
abstract = {INTRODUCTION: The splice variant of retinal G-protein-coupled receptor deletion (RGR-d) is a persistent component of drusen and may be involved in the pathogenesis of dry age-related macular degeneration (AMD). Increasing evidence has demonstrated the critical role of autophagy in AMD. In this study, we investigated whether RGR-d disrupts autophagy in early dry AMD in vivo and in vitro.<br><br>METHODS: Fundus imaging and fluoroscopy were performed on RGR-d mice created by multiplex gene editing. The retina microstructure was evaluated by performing hematoxylin and eosin (H&amp;E) staining as well as transmission electron microscopy (TEM). Retinal function was assessed by full-field electroretinography (ERG). After lentivirus transfection and stimulation, the permeability, phagocytosis, and tight junctions of ARPE-19 cells were evaluated. Western blotting of ATG5, Beclin-1, LC3II/I, and P62 was performed to detect the changes in autophagy pathways.<br><br>RESULTS: Atrophy and patchy penetrating hyperfluorescent foci, consistent with early AMD-like defects, were observed in the fundus of 12-month-old RGR-d mice. H&amp;E staining of retinal tissues indicated thinning of each layer of the retinal structure. H&amp;E staining of retinal tissues indicated thinning of each layer of the retinal structure. TEM analysis showed some diffuse granular deposits. And the morphology of choroidal microvascular endothelial cells was degraded and distorted. The morphology of the photoreceptor outer segments showed structural damage, and Bruch's membrane was thickened. ERG indicated that the photoreceptor of RGR-d mice were dysfunctional. Changes in autophagy-related protein expression were observed in the retinal pigment epithelium and retinal neurepithelium, and autophagy regulation was decreased. Palmitic acid (PA) stimulation caused permeability, phagocytosis, and tight junction dysfunction in cells overexpressing RGR-d. Beclin-1 and LC3II/I expression levels were significantly decreased and that of P62 was elevated in RGR-d cells after PA stimulation.<br><br>CONCLUSION: RGR-d disrupts the autophagy pathway, causing the development of an early AMD-like pathophysiology.},
}
@article {pmid39405051,
year = {2024},
author = {Tang, S and Yang, J and Xiao, B and Wang, Y and Lei, Y and Lai, D and Qiu, Q},
title = {Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {12},
pages = {20},
pmid = {39405051},
issn = {1552-5783},
mesh = {Humans ; *Complement Activation/physiology ; *Lipid Metabolism/physiology ; *Macular Degeneration/metabolism ; Retinal Pigment Epithelium/metabolism ; Complement System Proteins/metabolism ; },
abstract = {Age-related macular degeneration (AMD) stands as a leading cause of severe visual impairment and blindness among the elderly globally. As a multifactorial disease, AMD's pathogenesis is influenced by genetic, environmental, and age-related factors, with lipid metabolism abnormalities and complement system dysregulation playing critical roles. This review delves into recent advancements in understanding the intricate interaction between these two crucial pathways, highlighting their contribution to the disease's progression through chronic inflammation, drusen formation, and retinal pigment epithelium dysfunction. Importantly, emerging evidence points to dysregulated lipid profiles, particularly alterations in high-density lipoprotein levels, oxidized lipid deposits, and intracellular lipofuscin accumulation, as exacerbating factors that enhance complement activation and subsequently amplify tissue damage in AMD. Furthermore, genetic studies have revealed significant associations between AMD and specific genes involved in lipid transport and complement regulation, shedding light on disease susceptibility and underlying mechanisms. The review further explores the clinical implications of these findings, advocating for a novel therapeutic approach that integrates lipid metabolism modulators with complement inhibitors. By concurrently targeting these pathways, the dual-targeted approach holds promise in significantly improving outcomes for AMD patients, heralding a new horizon in AMD management and treatment.},
}
@article {pmid39404899,
year = {2025},
author = {Rein, AP and Totah, H and Brosh, K and Zadok, D and Hanhart, J},
title = {Foveal hyper-reflective vertical lines detected by optical coherence tomography: Imaging features, literature review and differential diagnoses.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {3},
pages = {849-855},
pmid = {39404899},
issn = {1435-702X},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Diagnosis, Differential ; Fluorescein Angiography/methods ; *Fovea Centralis/pathology/diagnostic imaging ; *Retinal Diseases/diagnosis ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Visual Acuity ; },
abstract = {PURPOSE: To describe foveal hyper-reflective vertical lines (FVL) as a specific morphological finding on structural spectral-domain optical coherence tomography (SD-OCT) and discuss its differential diagnosis.<br><br>METHODS: Observational case series. Ten patients (10 eyes) with FVL were meticulously examined at the Ophthalmology Department, Shaare Zedek Medical Center, Jerusalem, Israel. Detailed analysis of SD-OCT findings, clinical records, and retinal imaging was conducted to establish correlations between FVL and various underlying conditions.<br><br>RESULTS: We established the following list of settings, supported by the clinical context and ancillary investigations, in which SD-OCT displayed FVL: inflammation (1 eye), mechanical (1 eye), resorption of fluids of various origins (4 eyes), macular telangiectasia (1 eye), age-related macular degeneration (1 eye), diabetic retinopathy (1 eye) and scar (1 eye).<br><br>CONCLUSIONS: FVL can be observed in various underlying conditions. Recognition of this pattern and formulation of an appropriate differential diagnosis is of interest for correctly diagnosing and treating patients whose structural OCT harbors this yet overlooked finding.},
}
@article {pmid39400438,
year = {2025},
author = {Abdalla, S and Westborg, I and Pulkki-Brännström, AM and Norberg, H},
title = {Faricimab versus bevacizumab for neovascular age-related macular degeneration: Cost analysis based on real-world data from the Swedish Macula Registry.},
journal = {Acta ophthalmologica},
volume = {103},
number = {1},
pages = {99-108},
pmid = {39400438},
issn = {1755-3768},
support = {//Ume&#xe5; University/ ; },
mesh = {Humans ; *Bevacizumab/economics/administration &amp; dosage ; *Angiogenesis Inhibitors/economics/administration &amp; dosage ; Sweden ; Retrospective Studies ; *Registries ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/economics/diagnosis ; Male ; Female ; Aged ; *Cost-Benefit Analysis ; *Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Macula Lutea/pathology ; Aged, 80 and over ; Follow-Up Studies ; Tomography, Optical Coherence ; Treatment Outcome ; },
abstract = {PURPOSE: To analyse the impact on cost if faricimab is used as the first-line treatment for neovascular age-related macular degeneration (nAMD) compared to standard treatment with bevacizumab.<br><br>METHODS: Retrospective registry study including real-world data from the Swedish Macula Registry between 2017 and 2022. The observed number of injections and visits for bevacizumab during the first two years of treatment was used (n&#x2009;=&#x2009;437 patients). Number of faricimab injections was obtained from published clinical trial data and unit costs mostly from publicly available Swedish sources. The provider cost included medication and visit cost and societal cost included additionally patient travel cost. Costs are presented in 2023 EUR.<br><br>RESULTS: The incremental societal cost of faricimab was 277 EUR per patient compared to bevacizumab in the base case. Medication cost was higher (1516 EUR) while visit cost (-1183 EUR) and patient travel cost (-56 EUR) were lower due to longer injection intervals. Faricimab was of similar cost as bevacizumab for patients residing far from the clinic. The faricimab injection interval and the number of bevacizumab injections were major drivers of uncertainty in the results.<br><br>CONCLUSION: Faricimab represents a cost-effective alternative to bevacizumab for patients with nAMD in Sweden. Its extended treatment interval is particularly beneficial for patients living far from clinics, and if the real-life faricimab injection interval extends beyond 12&#x2009;weeks. Our findings emphasize faricimab's potential to free up healthcare staff to treat a larger patient population with existing clinic resources.},
}
@article {pmid39400101,
year = {2024},
author = {Firmani, G and Salducci, M and Testa, F and Covelli, GP and Sagnelli, P and Lambiase, A},
title = {Ocular Biomarkers in Alzheimer's Disease: Insights into Early Detection Through Eye-Based Diagnostics - A Literature Review.},
journal = {La Clinica terapeutica},
volume = {175},
number = {5},
pages = {352-361},
doi = {10.7417/CT.2024.5125},
pmid = {39400101},
issn = {1972-6007},
mesh = {*Alzheimer Disease/diagnosis/diagnostic imaging ; Humans ; *Early Diagnosis ; *Biomarkers/analysis ; *Tomography, Optical Coherence/methods ; Electroretinography/methods ; Eye Diseases/diagnosis ; Amyloid beta-Peptides/metabolism/analysis ; Diagnostic Techniques, Ophthalmological ; },
abstract = {Alzheimer's Disease (AD) is a significant challenge in neurodegenerative disorders, characterized by a gradual decline in cognitive functions. Diagnosis typically occurs at advanced stages when therapeutic options are less effective, underscoring the importance of early detection. Traditional diagnostic methods are often invasive and costly, spurring interest in more accessible and economical alternatives. The eye, as a direct link to the brain through the optic nerve, suggests that ocular changes could serve as early indicators of AD. This has led to the exploration of non-invasive ocular diagnostic tools. Technologies such as Optical Coherence Tomography (OCT), OCT Angiography (OCT-A), pupillometry, and eye-tracking, along with electrophysiological methods like Electroretinography (ERG) and Pattern Electroretinography (PEV), are being utilized to investigate potential ocular biomarkers. Further, tear fluid analysis has suggested that presence of amyloid-beta (Aβ) protein might reflect neurogenerative processes, providing a non-invasive window into disease progression. Exploring ocular changes as potential early indicators of Alzhei-mer's Disease (AD), we aimed to provide an overview of promising biomarkers for earlier diagnosis and intervention. Our review further investigates the connections between AD and other ocular degenera-tive diseases such as age-related macular degeneration (AMD) and glaucoma, uncovering shared pathogenic pathways that could offer new therapeutic targets. To establish the sensitivity and specificity of these ocular biomarkers, comprehensive studies are required. Moreover, larger, longitudinal studies are essential to confirm the effectiveness of ocular assessments in the preemptive diagnosis of Alzheimer's Disease.},
}
@article {pmid39399049,
year = {2024},
author = {Farashi, S and Abbott, CJ and Ansell, BR and Wu, Z and Altay, L and Arnon, E and Arnould, L and Bagdasarova, Y and Balaskas, K and Chen, FK and Chew, E and Chowers, I and Clarke, S and Cukras, C and Delcourt, C and Delyfer, MN and den Hollander, AI and Fauser, S and Finger, RP and Gabrielle, PH and Han, J and Hodgson, LA and Hogg, R and Holz, FG and Hoyng, C and Kumar, H and Lad, EM and Lee, A and Luhmann, UF and Mauschitz, MM and McKnight, AJ and McLenachan, S and Mishra, A and Moghul, I and Orozco, LD and Sampson, DM and Scott, LW and Sitnilska, V and Song, S and Stockwell, A and Swaroop, A and Terheyden, JH and Tiosano, L and Tufail, A and Yaspan, BL and , and , and Pébay, A and Fletcher, EL and Guymer, RH and Bahlo, M},
title = {Genetic Risk of Reticular Pseudodrusen in Age-Related Macular Degeneration: HTRA1 /lncRNA BX842242.1 dominates, with no evidence for Complement Cascade involvement.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.09.26.24314339},
pmid = {39399049},
abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2,165 AMD+/RPD+ and 4,181 AMD+/RPD-compared to 7,660 control participants, both chromosomes 1 (CFH) and 10 (ARMS2/HTRA1) major AMD risk loci were reidentified. However association was only detected for the chromosome 10 locus when comparing AMD+/RPD+ to AMD+/RPD-cases. The chromosome 1 locus was notably absent. The chromosome 10 RPD risk region contains a long non-coding RNA (ENSG00000285955/BX842242.1) which colocalizes with genetic markers of retinal thickness. BX842242.1 has a strong retinal eQTL signal, pinpointing the parafoveal photoreceptor outer segment layer. Whole genome sequencing of phenotypically extreme RPD cases identified even stronger enrichment for the chromosome 10 risk genotype.},
}
@article {pmid39398467,
year = {2024},
author = {Modeste, D and Stewart, C and Premanandhan, H and Awad, MH and Williams, GS},
title = {Evaluating Faricimab in Treatment-Naive Neovascular Age Related Macular Degeneration: A Retrospective Analysis of Real-World Data.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {2821-2829},
pmid = {39398467},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the efficiency and safety of Faricimab on treatment-naive neovascular age related macular degeneration (nAMD) in a real world UK clinic.<br><br>PATIENTS AND METHODS: This single centre, retrospective note review was conducted on treatment-naive patients with nAMD. The data collected included demographics, best corrected visual acuity (BCVA), central macular thickness (CMT), total retinal fluid (TRF), the presence of intraretinal fluid (IRF) and subretinal fluid (SRF).<br><br>RESULTS: A total of 66 eyes from 62 patients were analysed. The average age was 77 years (range 36-91) and 54% of patients were female. After the first dose of faricimab, the average BCVA improved by 0.05 LogMAR (+2.5 letters), the average CMT decreased by 65.9&#x3bc;m and 41% of patients were found to be inactive. The follow-up intervals after the third loading dose were divided into 2 subsets of 4 and 8&#xa0;week extensions. The 4&#xa0;week extension subset saw a smaller improvement in BCVA (+3 letters) than the 8&#xa0;week extension (+6 letters) while both had an average decrease in CMT by 86.6&#xa0;&#x3bc;m. The total retinal fluid decreased by 45% and 70.7%, leaving only 30% and 12.2% residual intraretinal fluid (IRF) and 30% and 24.4% residual subretinal fluid (SRF), respectively. Over a ten-month period, the average number of injections received was 6.6, including 3 initial loading doses. There was only one reported case of an adverse event out of 66 eyes (1/66, 1.5%).<br><br>CONCLUSION: Three loading doses of Faricimab appear efficacious and safe for the treatment of nAMD.},
}
@article {pmid39398231,
year = {2024},
author = {Zhang, S and Penkova, A and Jia, X and Sebag, J and Sadhal, SS},
title = {Effective Prediction of Drug Transport in a Partially Liquefied Vitreous Humor: Physics-informed Neural Network Modeling for Irregular Liquefaction Geometry.},
journal = {Engineering applications of artificial intelligence},
volume = {138},
number = {Pt A},
pages = {},
pmid = {39398231},
issn = {0952-1976},
support = {R01 EY026599/EY/NEI NIH HHS/United States ; },
abstract = {As the medium for intravitreal drug delivery, the vitreous body can significantly influence drug delivery because of various possible liquefaction geometries. This work innovatively proposes a varying-porosity approach that is capable of solving the pressure and velocity fields in the heterogeneous vitreous with randomly-shaped liquefaction geometry, validated with a finite difference model. Doing so enables patient-specific treatment for intravitreal drug delivery and can significantly improve treatment efficacy. A physics-informed neural network (PINN) model is also established for the simulation, and three cases are used for validation. Despite limited information, the PINN model, together with the varying-porosity approach, captured fluid and drug transport in the partially liquefied vitreous. This opens the possibility for optimizing intravitreal drug delivery based on ultrasonography in clinical practice.},
}
@article {pmid39388167,
year = {2024},
author = {Cozzi, M and Ziegler, A and Fasler, K and Muth, DR and Blaser, F and Zweifel, SA},
title = {Sterile Intraocular Inflammation Associated With Faricimab.},
journal = {JAMA ophthalmology},
volume = {142},
number = {11},
pages = {1028-1036},
pmid = {39388167},
issn = {2168-6173},
abstract = {IMPORTANCE: Randomized clinical trials are conducted to establish both drug safety and efficacy. However, evidence of adverse events associated with these drugs in the clinical practice setting can be of value at generating hypotheses regarding less common safety issues, even if causality cannot be determined.<br><br>OBJECTIVE: To present and analyze cases of intraocular inflammation associated with faricimab therapy in patients referred to a single European institution.<br><br>This was a review starting in April of 2024 of an observational case series. Patients were from a single academic-based tertiary referral center in Switzerland. Included in the analysis were patients referred for intraocular inflammation soon after receiving a faricimab intravitreal injection between June 1, 2022, and March 5, 2024.<br><br>EXPOSURE: Faricimab, 6 mg (0.05 mL of a 120-mg/mL solution), administrated for neovascular age-related macular degeneration or diabetic macular edema.<br><br>MAIN OUTCOMES AND MEASURES: The systemic and ocular histories and imaging data available were reviewed. The following were evaluated: visual acuity measured with habitual correction using the Early Treatment of Diabetic Retinopathy Study charts before and after the event; intraocular pressure; patient symptoms; anterior, intermediate, or posterior location of the intraocular inflammation; and the presence of retinal vasculitis. Multimodal imaging including color fundus photographs, fluorescein angiograms, indocyanine green angiograms, and optical coherence tomography were reviewed.<br><br>RESULTS: A total of 12 eyes from 7 patients (mean [SD] age, 73.3 [16.7] years; 4 female [57.1%]) over 22 months were identified as having noninfectious intraocular inflammation after intravitreal faricimab injections. Among these cases, in 2 eyes, retinal vasculitis was present together with anterior and posterior inflammation. One of the 2 eyes had an occlusive form of vasculitis of the arteries and veins, leading to subsequent macular capillary nonperfusion and clinically relevant irreversible vision deterioration from 20/80 to 20/2000. The remaining eyes were characterized by moderate anterior segment inflammation without substantial vision changes. The intraocular inflammation event occurred after a median (IQR) of 3.5 (2.0-4.3) faricimab injections. The median (IQR) interval between the last faricimab injection and the diagnosis of inflammation was 28 (24-38) days. Increased intraocular pressure of 30 mm Hg or higher was found in 3 eyes.<br><br>CONCLUSIONS AND RELEVANCE: This case series highlights the occurrence of rare, but potentially severe, intraocular inflammation associated with faricimab therapy. Although these findings do not prove causality and can only generate hypotheses for future investigations, these results suggest the importance of continuous surveillance and monitoring for patients undergoing faricimab therapy to promptly identify and manage potential adverse events.},
}
@article {pmid39387705,
year = {2025},
author = {Ryan, B and Jones, M and Anderson, P and Reynolds, R and Nicholls, REM and Cullen, K and Davies, M and North, R and Molik, B and Wallace, C},
title = {Hospital to community in Wales: What is the value of optometrists playing a greater role in managing neovascular AMD and glaucoma in primary care?.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {1},
pages = {280-293},
pmid = {39387705},
issn = {1475-1313},
support = {RFPB-19-1639/HCRW/HCRW_/United Kingdom ; RFPB-19-1639/HCRW/HCRW_/United Kingdom ; },
mesh = {Humans ; *Primary Health Care/organization &amp; administration ; Wales ; *Optometrists ; *Glaucoma/therapy/diagnosis ; *Optometry/organization &amp; administration ; Wet Macular Degeneration/therapy/diagnosis ; Male ; Female ; },
abstract = {PURPOSE: To evaluate the value of enhanced optometric services for managing neovascular age-related macular degeneration (nAMD) and glaucoma in primary care optometry services, instead of hospital eye services (HES).<br><br>METHODS: Seven enhanced optometric service pathways in primary care in Wales were assessed with a mixed-methods approach: three for nAMD and four for glaucoma. The methods were a patient-related experience measure (PREM), a Realist Review and Evaluation involving both patients and staff, a discrete event simulation model estimating the economic impact of the pathways and a workforce survey of optometrists to gauge capability and capacity.<br><br>RESULTS: Patient-related experience measure responses (802) indicated that primary care experience was comparable to that of HES. Utilising enhanced optometric services in primary care resulted in reduced wait times compared with HES, with suspected nAMD shortened to 4-5&#x2009;days and glaucoma monitoring to 5&#x2009;days. Waiting lists were dramatically reduced with primary care-based services to just three people waiting for nAMD and five for glaucoma, compared with 216 and 5691 people, respectively, in HES. Consultant ophthalmologist time was reduced from 57% to 15%-16% for nAMD services and from 48% to 22%-23% for glaucoma services. Integrating enhanced optometric services into primary care incurred a similar cost. The workforce survey confirms that optometrists possess the skills and qualifications and are willing to deliver these enhanced optometric services. The Realist Review and Evaluation revealed that clear patient communication, effective coordination and strong interprofessional communication between optometrists and ophthalmologists along with a shared electronic record are crucial to the success of this change.<br><br>CONCLUSION: Providing enhanced optometric services in primary care for nAMD and glaucoma brings substantial benefits for the UK National Health Service and patients, including reduced waiting times, waiting lists and released HES capacity. The success of this transition hinges on clear patient communication, administrative co-ordination and effective interprofessional communication.},
}
@article {pmid39395210,
year = {2025},
author = {Pachade, S and Porwal, P and Kokare, M and Deshmukh, G and Sahasrabuddhe, V and Luo, Z and Han, F and Sun, Z and Qihan, L and Kamata, SI and Ho, E and Wang, E and Sivajohan, A and Youn, S and Lane, K and Chun, J and Wang, X and Gu, Y and Lu, S and Oh, YT and Park, H and Lee, CY and Yeh, H and Cheng, KW and Wang, H and Ye, J and He, J and Gu, L and Müller, D and Soto-Rey, I and Kramer, F and Arai, H and Ochi, Y and Okada, T and Giancardo, L and Quellec, G and Mériaudeau, F},
title = {RFMiD: Retinal Image Analysis for multi-Disease Detection challenge.},
journal = {Medical image analysis},
volume = {99},
number = {},
pages = {103365},
doi = {10.1016/j.media.2024.103365},
pmid = {39395210},
issn = {1361-8423},
mesh = {Humans ; *Retinal Diseases/diagnostic imaging ; Image Interpretation, Computer-Assisted/methods ; Deep Learning ; Fundus Oculi ; Datasets as Topic ; Diabetic Retinopathy/diagnostic imaging ; Databases, Factual ; },
abstract = {In the last decades, many publicly available large fundus image datasets have been collected for diabetic retinopathy, glaucoma, and age-related macular degeneration, and a few other frequent pathologies. These publicly available datasets were used to develop a computer-aided disease diagnosis system by training deep learning models to detect these frequent pathologies. One challenge limiting the adoption of a such system by the ophthalmologist is, computer-aided disease diagnosis system ignores sight-threatening rare pathologies such as central retinal artery occlusion or anterior ischemic optic neuropathy and others that ophthalmologists currently detect. Aiming to advance the state-of-the-art in automatic ocular disease classification of frequent diseases along with the rare pathologies, a grand challenge on "Retinal Image Analysis for multi-Disease Detection" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2021). This paper, reports the challenge organization, dataset, top-performing participants solutions, evaluation measures, and results based on a new "Retinal Fundus Multi-disease Image Dataset" (RFMiD). There were two principal sub-challenges: disease screening (i.e. presence versus absence of pathology - a binary classification problem) and disease/pathology classification (a 28-class multi-label classification problem). It received a positive response from the scientific community with 74 submissions by individuals/teams that effectively entered in this challenge. The top-performing methodologies utilized a blend of data-preprocessing, data augmentation, pre-trained model, and model ensembling. This multi-disease (frequent and rare pathologies) detection will enable the development of generalizable models for screening the retina, unlike the previous efforts that focused on the detection of specific diseases.},
}
@article {pmid39394372,
year = {2025},
author = {Faes, L and Bijon, J and Bacci, T and Freund, KB},
title = {Review of type 3 macular neovascularization in age-related macular degeneration: no DRAMA (Deep Retinal Age-related Microvascular Anomalies).},
journal = {Eye (London, England)},
volume = {39},
number = {5},
pages = {870-882},
pmid = {39394372},
issn = {1476-5454},
mesh = {Humans ; *Retinal Vessels/pathology ; Retinal Pigment Epithelium/pathology ; *Retinal Neovascularization/diagnosis ; *Macular Degeneration/diagnosis ; *Wet Macular Degeneration/diagnosis ; Tomography, Optical Coherence ; Fluorescein Angiography ; },
abstract = {Type 3 macular neovascularization (MNV) is a unique form of neovascular age-related macular degeneration (AMD) that presents distinct pathogenetic features, clinical manifestations, and prognostic considerations when compared to types 1 and 2 MNV. Insights gained from clinicopathological correlations, bridging in vivo examination techniques with ex vivo histological analysis, have significantly enhanced our comprehension of this MNV phenotype, shaped current management strategies and influenced future directions for therapeutics. The particularities of type 3 MNV, which may largely stem from its origin from the retinal vasculature, are critically important for predicting the disease course. Our current understanding suggests that type 3 MNV occurs in response to retinal pigment epithelium (RPE) disruption and photoreceptor loss when neovessels originating from the deep capillary plexus are accompanied by activated Müller glia as they infiltrate sub-retinal pigment epithelium basal laminar deposits. Dysregulation of angiogenic and angiostatic factors are thought to play a key role in its pathogenesis. The prognosis for type 3 MNV is likely bilateral involvement and progression towards macular atrophy. It may be imperative for practitioners to distinguish type 3 MNV from other mimicking pathologies such as intraretinal microvascular anomalies, which are also part of the type 3 disease spectrum. For instance, deep retinal age-related microvascular anomalies (DRAMA) may present with similar features on multimodal imaging yet may necessitate distinct management protocols. Distinguishing between these conditions may be vital for implementing tailored treatment regimens and improving patient outcomes in the diverse landscape of AMD phenotypes in the future.},
}
@article {pmid39394370,
year = {2024},
author = {Borchert, GA and Kiire, CA and Stone, NM and Akil, H and Gkika, T and Fischer, MD and Xue, K and Cehajic-Kapetanovic, J and MacLaren, RE and Charbel Issa, P and Downes, SM and De Silva, SR},
title = {Real-world six-month outcomes in patients switched to faricimab following partial response to anti-VEGF therapy for neovascular age-related macular degeneration and diabetic macular oedema.},
journal = {Eye (London, England)},
volume = {38},
number = {18},
pages = {3569-3577},
pmid = {39394370},
issn = {1476-5454},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Macular Edema/drug therapy/physiopathology ; Retrospective Studies ; *Visual Acuity/physiology ; Aged ; *Diabetic Retinopathy/drug therapy/physiopathology ; *Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Wet Macular Degeneration/drug therapy/physiopathology ; Tomography, Optical Coherence ; Treatment Outcome ; Drug Substitution ; Middle Aged ; Ranibizumab/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; Bevacizumab/therapeutic use/administration &amp; dosage ; },
abstract = {BACKGROUND: Landmark studies reported on faricimab efficacy and safety predominantly in treatment naïve patients, but outcomes following switch from other anti-VEGF therapies are lacking. We evaluated patients switched to faricimab who had previously shown a partial response to other anti-VEGF injections for neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO).<br><br>METHODS: Retrospective study at the Oxford Eye Hospital. Patients switched to faricimab from January to April 2023 with six months follow-up were identified via electronic medical records.<br><br>RESULTS: A total of 116 patients (151 eyes) were included. In 88 patients with nAMD (107 eyes), mean visual acuity remained stable: 62&#xb1;17 ETDRS letters at baseline; 62&#xb1;18 at six months (p&#x2009;>&#x2009;0.05). Central subfield thickness (CST) reduced from 294&#x2009;&#xb1;&#x2009;73&#x2009;&#x3bc;m to 270&#x2009;&#xb1;&#x2009;53&#x2009;&#x3bc;m (p&#x2009;<&#x2009;0.05) at six months. Subretinal or intraretinal fluid was present in 102 eyes (95%) at baseline and 75 eyes (70%) at follow-up (p&#x2009;<&#x2009;0.05). Pigment epithelial detachment height decreased from 233&#x2009;&#xb1;&#x2009;134&#x2009;&#x3bc;m to 188&#x2009;&#xb1;&#x2009;147&#x2009;&#x3bc;m (p&#x2009;<&#x2009;0.05). Mean treatment interval increased by 1.7 weeks (p&#x2009;<&#x2009;0.05) and was extended in 61 eyes (57%) at six months. In 28 patients with DMO (44 eyes), visual acuity remained stable: 69&#x2009;&#xb1;&#x2009;15 letters at baseline; 70&#xb1;15 at six months (p&#x2009;>&#x2009;0.05). CST reduced from 355&#x2009;&#xb1;&#x2009;87&#x2009;&#x3bc;m to 317&#x2009;&#xb1;&#x2009;82&#x2009;&#x3bc;m (p&#x2009;<&#x2009;0.05). Mean treatment interval increased by 1.4 weeks (p&#x2009;<&#x2009;0.05) and was extended in 21 eyes (46%) by six months.<br><br>CONCLUSIONS: Switching to faricimab in treatment resistant eyes led to improved anatomical response and extended treatment interval in a significant proportion of patients. Ongoing review of real-world data will inform longer-term outcomes of safety and effectiveness.},
}
@article {pmid39392292,
year = {2024},
author = {Płatkowska-Adamska, B and Bociek, A and Kal, M and Zarębska-Michaluk, D and Odrobina, D},
title = {BNT162b2 vaccine booster dose did not influence the activity of the exudative form of age-related macular degeneration during anti-vascular endothelial growth factor therapy.},
journal = {Minerva medica},
volume = {115},
number = {6},
pages = {643-650},
doi = {10.23736/S0026-4806.24.09379-0},
pmid = {39392292},
issn = {1827-1669},
mesh = {Humans ; *BNT162 Vaccine/administration &amp; dosage/adverse effects ; Male ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use/adverse effects ; Aged ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Ranibizumab/administration &amp; dosage ; *Tomography, Optical Coherence ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Aged, 80 and over ; *Intravitreal Injections ; Macular Degeneration/drug therapy ; Immunization, Secondary ; COVID-19 Vaccines/adverse effects/administration &amp; dosage ; Visual Acuity ; COVID-19/prevention &amp; control ; Wet Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {BACKGROUND: Due to safety concerns, patients were hesitant to receive a booster dose of COVID-19 vaccine. In this study, we investigated whether neovascular age-related macular degeneration activity deteriorated after receiving the booster dose of the BNT162b2 vaccine.<br><br>METHODS: Optical coherence tomography (OCT) of the macula, best-corrected visual acuity (BCVA), and slit-lamp examination data were collected from 89 patients. All these individuals were diagnosed with neovascular age-related macular degeneration (AMD) and treated with intravitreal injections of aflibercept or ranibizumab. During the process of treatment, patients received a booster dose of the BNT162b2 vaccine. Time points included two visits before (marked as "-2", "-1") and two visits after (marked as "1", "2") the uptake of the booster dose.<br><br>RESULTS: There were significant differences in the average thickness and total volume of the macula during follow-up. Moreover, a decreased average thickness, total volume, total thickness of the macula, subretinal fluid thickness, and subretinal complex thickness was observed between the time points "-2" and "2", but only in the aflibercept group. There were no significant differences in the frequency of occurring intraretinal cysts, subretinal fluid, serous retinal pigment epithelial detachments retinal hemorrhage, subretinal hyperreflective material, complete RPE and outer retinal atrophy, and BCVA before and after the booster dose.<br><br>CONCLUSIONS: These results demonstrate that the BNT162b2 vaccine booster dose did not deteriorate the course of neovascular AMD.},
}
@article {pmid39392113,
year = {2025},
author = {Su, S and Yang, Y and Chen, J and Zhang, S and Yang, X and Sang, A},
title = {TLR4/TRIF/Caspase-8/Caspase-1 Pathway in Choroidal Endothelial Cells Promotes Choroidal Neovascularization.},
journal = {Current eye research},
volume = {50},
number = {2},
pages = {203-212},
doi = {10.1080/02713683.2024.2409885},
pmid = {39392113},
issn = {1460-2202},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology ; *Caspase 8/metabolism ; Mice ; Humans ; *Choroid/blood supply/metabolism/pathology ; Disease Models, Animal ; Mice, Inbred C57BL ; *Toll-Like Receptor 4/metabolism ; *Caspase 1/metabolism ; Signal Transduction/physiology ; Cells, Cultured ; Blotting, Western ; *Endothelial Cells/metabolism/pathology ; Male ; },
abstract = {PURPOSE: The purpose of this study was to investigate the role and mechanism of caspase-8 in the development of choroidal neovascularization induced by age-related macular degeneration, with the aim of identifying a potential therapeutic target for neovascular age-related macular degeneration.<br><br>METHODS: Mouse models of laser photocoagulation-induced choroidal neovascularization and hypoxic human choroidal endothelial cells were utilized to examine the involvement of caspase-8 in choroidal neovascularization development. The toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8 pathway was explored in hypoxic human choroidal endothelial cells to elucidate its contribution to pathological angiogenesis. Various experimental techniques, including inhibition assays and immunoblotting analysis, were employed to assess the effects and mechanisms of caspase-8 activation.<br><br>RESULTS: Inhibition of caspase-8 demonstrated attenuated choroidal neovascularization development in mice subjected to laser photocoagulation. Activation of the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8 pathway was observed in hypoxic human choroidal endothelial cells. Upon activation by the toll-like receptor 4/TIR domain-containing adaptor molecule 1 axis, caspase-8 directly cleaved caspase-1, leading to the cleavage of interleukin-1&#x3b2; and interleukin-18 by caspase-1. Consequently, activation of interleukin-1&#x3b2; and interleukin-18 through the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8/caspase-1 pathway promoted the proliferative, migratory, and tube-forming abilities of hypoxic human choroidal endothelial cells.<br><br>CONCLUSION: The findings of this study indicate that caspase-8 plays a crucial role in promoting choroidal neovascularization by activating interleukin-1&#x3b2; and interleukin-18 through the toll-like receptor 4/TIR domain-containing adaptor molecule 1/caspase-8/caspase-1 pathway in choroidal endothelial cells. Therefore, targeting caspase-8 may hold promise as a therapeutic approach for neovascular age-related macular degeneration.},
}
@article {pmid39391760,
year = {2024},
author = {Kammoun, S and Rekik, M and Dlensi, A and Aloulou, S and Smaoui, W and Sellami, S and Trigui, K and Gargouri, R and Chaari, I and Sellami, H and Elatoui, D and Khemakhem, N and Hadrich, I and Neji, S and Abdelmoula, B and Bouayed Abdelmoula, N},
title = {The gut-eye axis: the retinal/ocular degenerative diseases and the emergent therapeutic strategies.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1468187},
pmid = {39391760},
issn = {1662-5102},
abstract = {The interplay between human microbiota and various physiological systems has garnered significant attention in recent years. The gut microbiota plays a critical role in maintaining physiological homeostasis and influences various aspects of human health, particularly via the gut brain axis. Since 2017, the challenging concept of the gut-retina axis has emerged thanks to a network analysis emphasizing the potential role of the gut microbiota disruption in the development of the age-related macular degeneration and further retinal damages. Many other ocular disorders have been linked to the dysbiosis of the gut microbiota, including uveitis and glaucoma. It has been shown that age related macular degeneration can be prevented or reversed using a diet that induces changes in the gut microbiota. The potential link between the gut microbiota as well as others types of microbiota such as the ocular surface microbiota and the development/progression of age related as well as inherited retinal degenerations and other degenerative eye diseases, has recently been broadened. Therefore, the pathogenesis of several eye diseases has recently been associated with a larger perception called the gut eye axis. This mini-review examines the potential mechanisms underlying the gut eye axis and suggests implications for the management of eye diseases. By understanding the modulation of the gut microbiota and its impact on eye disease, this mini-review provides insight into potential therapeutic interventions and avenues for future research.},
}
@article {pmid39389463,
year = {2025},
author = {Hamouz, J and Nowosielska, A and Święch-Zubilewicz, A and Abengoechea, S and Baumane, K and Vajas, A and Siewierska, M and Veselovsky, M and Veith, M and Kerényi, &#xc1; and Mange, S and Baidya, K and Laganovska, G and Jürgens, I and Papp, A and Gosai, J and Štefanickova, J and Han, M and Fryczkowski, P and Zalewski, D and Wang, J and Wei, W},
title = {Efficacy and Safety of Ranibizumab Biosimilar QL1205 in Neovascular Age-Related Macular Degeneration: A Phase III Randomized Trial.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {4},
pages = {343-351},
doi = {10.1016/j.oret.2024.10.001},
pmid = {39389463},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Biosimilar Pharmaceuticals/administration &amp; dosage/adverse effects ; Dose-Response Relationship, Drug ; Double-Blind Method ; Follow-Up Studies ; Intravitreal Injections ; *Ranibizumab/administration &amp; dosage/adverse effects ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {OBJECTIVE: This study aimed to demonstrate the clinical equivalence of biosimilar QL1205 and reference ranibizumab, Lucentis, in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: This was a multicenter, double-masked, randomized, controlled phase III trial.<br><br>PARTICIPANTS: Treatment-naive patients with active nAMD were randomly assigned to receive QL1205 or reference ranibizumab.<br><br>METHODS: Patients received intravitreal injection of QL1205 or reference ranibizumab at a dose of 0.5 mg in the study eye once every 4 weeks for 48 weeks.<br><br>MAIN OUTCOME MEASURES: The primary end point was change in best-corrected visual acuity (BCVA) by ETDRS letters at week 8 compared with baseline level. Biosimilarity of QL1205 to reference ranibizumab was assessed with an equivalence range for the difference in BCVA letters between&#xa0;-3.49 and&#xa0;+3.49.<br><br>RESULTS: Between June 27, 2019 and June 8, 2021, 616 patients were randomized to the QL1205 group (n&#xa0;= 308) and the reference ranibizumab group (n&#xa0;= 308). The mean improvement of BCVA was&#xa0;+6.3 &#xb1; 9.13 ETDRS letters in the QL1205 group and&#xa0;+7.3 &#xb1; 8.82 ETDRS letters in the reference ranibizumab group at week 8. Both the 90% confidence interval (CI,&#xa0;-2.23 to 0.13) and 95% CI (-2.46 to 0.36) of the difference between the 2 treatment groups (P&#xa0;= 0.1434) were within the predefined equivalence range. Safety profiles were manageable in both groups.<br><br>CONCLUSIONS: QL1205 was biosimilar to reference ranibizumab regarding clinical efficacy, ocular and systemic safety, as well as immunogenicity and pharmacokinetics profiles in the treatment of patients with nAMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39389406,
year = {2025},
author = {Cheng, Y and Fleckenstein, M and Schmitz-Valckenberg, MS and Lu, J and Liu, Z and Herrera, G and Gregori, G and Wang, RK and Rosenfeld, PJ and Trivizki, O},
title = {Comparison Between Optical Coherence Tomography B-scan and En Face Imaging for the Diagnosis of Early Macular Atrophy in Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {270},
number = {},
pages = {252-260},
pmid = {39389406},
issn = {1879-1891},
support = {R01 EY028753/EY/NEI NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY033365/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY034965/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Prospective Studies ; Female ; Male ; Aged ; Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; *Macular Degeneration/diagnosis/complications ; Atrophy ; Middle Aged ; *Geographic Atrophy/diagnosis ; Visual Acuity ; },
abstract = {PURPOSE: The gradings of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) and incomplete RPE and outer retinal atrophy (iRORA) on spectral domain optical coherence tomography (SD-OCT) B-scans were compared with the grading of persistent choroidal hypertransmission defects (hyperTDs) on swept-source optical coherence tomography angiography (SS-OCTA) en face images.<br><br>DESIGN: Comparative diagnostic analysis of prospective study data.<br><br>METHODS: Patients with late nonexudative age-related macular degeneration underwent same-day 6&#xd7;6-mm macular scans using both SD-OCT (Spectralis Heidelberg, 512&#xd7;97, automatic real-time tracking: 9) and SS-OCTA (PLEX Elite 9000, Carl Zeiss Meditec, 500&#xd7;500 angio pattern) instruments. SS-OCTA and SD-OCT en face images were generated from a sub-RPE slab positioned 64 to 400 &#xb5;m below Bruch's membrane. SD-OCT B-scan gradings, which included an inspection of neighboring B-scans for the diagnosis of cRORA and iRORA, were performed at the Moran Eye Center, and gradings of en face images to identify persistent choroidal hyperTDs were performed at the Bascom Palmer Eye Institute and Tel Aviv Medical Center.<br><br>RESULTS: There was a high degree of agreement (99.6%) between the gradings of cRORA lesions and persistent hyperTDs. However, 27.4% of iRORA lesions were found to be contained within persistent hyperTDs. This discrepancy was due to the finding that 27.5% of iRORA lesions were diagnosed as having a greatest linear horizontal dimension of <250 &#xb5;m on B-scans, but on en face images, these B-scan-defined iRORA lesions were found to have the greatest linear dimensions in the nonhorizontal dimension that were &#x2265;250 &#xb5;m.<br><br>CONCLUSIONS: This report demonstrates the benefits of using en face OCT imaging to identify cRORA lesions and highlights the need to acquire dense raster B-scans with the grading neighboring B-scans when identifying iRORA lesions to assess the full extent of the iRORA lesions in the nonhorizontal dimension. Although neighboring B-scans were inspected, 27.5% of iRORA lesions were actually part of larger cRORA lesions when graded using an en face strategy.},
}
@article {pmid39386174,
year = {2024},
author = {Badalà, F and Bona, E and Devincenzi, G and Nouri-Mahdavi, K},
title = {Long Term Visual Outcomes of an Extended Macular Vision IOL in Eyes with Macular Disease and Visually Insignificant Cataract.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {2765-2775},
pmid = {39386174},
issn = {1177-5467},
abstract = {PURPOSE: To determine long-term efficacy and safety of an extended macular vision intraocular lens (IOL) implanted in patients with dry age-related macular degeneration (AMD) and visually insignificant cataracts.<br><br>DESIGN: Retrospective observational case series.<br><br>SETTING: MicroChirurgia Oculare, Italy.<br><br>METHODS: A retrospective case series of patients with dry AMD and visually insignificant cataracts undergoing phacoemulsification and implantation of an extended macular vision IOL designed to optimize image quality up to 10&#xb0; from the foveal center (EyeMax Mono, Sharpview Ophthalmology, London, UK). Criteria for implantation were visually insignificant cataract (NC1 according to LOCS III classification) with dry age-related macular degeneration. Hypermetropia was targeted in most eyes to provide magnification when corrected with spectacles. Primary outcome measures were changes in corrected distant and secondary outcome measures included near visual acuity (CDVA and CNVA, respectively) between baseline and latest follow-up and safety outcomes.<br><br>RESULTS: 113 eyes of 86 patients (mean age 70.3&#xb1;7.9 years) were included (mean follow-up: 48.3&#xb1;25.1 months). Mean CDVA improved by 0.22 logMAR (11 ETDRS letters), from 0.53&#xb1;0.4 to 0.31&#xb1;0.3 (n=113, p<0.001). Similarly, mean CNVA improved by 0.08 logMAR (4 ETDRS letters), from 0.45&#xb1;0.2 to 0.37&#xb1;0.2 (n=77, p<0.001). Eleven eyes had AMD with extensive atrophy, and their mean CDVA improved by 0.32 logMAR (16 ETDRS letters). Three eyes (2.7%) experienced loss of more than one line in logMAR CDVA and four eyes (5.2%) experienced loss of more than one line in logMAR CNVA. No complications or instances of IOL exchange were reported.<br><br>CONCLUSION: Visual improvement in eyes with visually insignificant cataract and AMD who underwent phacoemulsification and were implanted with EyeMax Mono IOL appears to be influenced by the IOL optical design. Vision enhancement in eyes with visually insignificant cataracts underscores the IOL's ability to optimize use of healthy retinal areas. Prospective studies with control groups are needed to confirm these findings.},
}
@article {pmid39386050,
year = {2024},
author = {do Nascimento, THO and Pereira-Figueiredo, D and Veroneze, L and Nascimento, AA and De Logu, F and Nassini, R and Campello-Costa, P and Faria-Melibeu, ADC and Souza Monteiro de Araújo, D and Calaza, KC},
title = {Functions of TRPs in retinal tissue in physiological and pathological conditions.},
journal = {Frontiers in molecular neuroscience},
volume = {17},
number = {},
pages = {1459083},
pmid = {39386050},
issn = {1662-5099},
abstract = {The Transient Receptor Potential (TRP) constitutes a family of channels subdivided into seven subfamilies: Ankyrin (TRPA), Canonical (TRPC), Melastatin (TRPM), Mucolipin (TRPML), no-mechano-potential C (TRPN), Polycystic (TRPP), and Vanilloid (TRPV). Although they are structurally similar to one another, the peculiarities of each subfamily are key to the response to stimuli and the signaling pathway that each one triggers. TRPs are non-selective cation channels, most of which are permeable to Ca[2+], which is a well-established second messenger that modulates several intracellular signaling pathways and is involved in physiological and pathological conditions in various cell types. TRPs depolarize excitable cells by increasing the influx of Ca[2+], Na[+], and other cations. Most TRP families are activated by temperature variations, membrane stretching, or chemical agents and, therefore, are defined as polymodal channels. All TPRs are expressed, at some level, in the central nervous system (CNS) and ocular-related structures, such as the retina and optic nerve (ON), except the TRPP in the ON. TRPC, TRPM, TRPV, and TRPML are found in the retinal pigmented cells, whereas only TRPA1 and TRPM are detected in the uvea. Accordingly, several studies have focused on the search to unravel the role of TRPs in physiological and pathological conditions related to the eyes. Thus, this review aims to shed light on endogenous and exogenous modulators, triggered cell signaling pathways, and localization and roles of each subfamily of TRP channels in physiological and pathological conditions in the retina, optic nerve, and retinal pigmented epithelium of vertebrates.},
}
@article {pmid39384883,
year = {2024},
author = {Kim, HM and Joo, K and Kim, M and Park, YJ and Han, JW and Kim, KW and Lee, S and Woo, SJ},
title = {Genome-wide association study of subfoveal choroidal thickness in a longitudinal cohort of older adults.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {23545},
pmid = {39384883},
issn = {2045-2322},
mesh = {Humans ; *Genome-Wide Association Study ; *Choroid/pathology ; Aged ; *Polymorphism, Single Nucleotide ; Male ; Female ; Longitudinal Studies ; Aged, 80 and over ; Macular Degeneration/genetics/pathology ; Human Umbilical Vein Endothelial Cells ; Cohort Studies ; Genetic Predisposition to Disease ; Genotype ; },
abstract = {To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10[-4] in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 μm (AA, 73.8%) and 31.1 μm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 μm (AA, 74.2%) and 28.2 μm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration.},
}
@article {pmid39384214,
year = {2024},
author = {Schmucker, C and Lagrèze, WA},
title = {Multifocal Optics for Myopia Control.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {241},
number = {10},
pages = {1129-1133},
doi = {10.1055/a-2397-1660},
pmid = {39384214},
issn = {1439-3999},
mesh = {Humans ; *Eyeglasses ; *Myopia/therapy/physiopathology ; Treatment Outcome ; Child ; Evidence-Based Medicine ; Equipment Design ; Adolescent ; Equipment Failure Analysis ; },
abstract = {The rising prevalence of myopia among children and adolescents necessitates effective interventions to mitigate long-term risks, such as retinal detachment and macular degeneration. Traditional approaches like undercorrection with single-vision lenses have proven ineffective. Recent research underscores the significance of peripheral vision in managing myopia progression. While hyperopic defocus in the peripheral retina may encourage axial elongation, multifocal lenses designed to induce peripheral myopic defocus can potentially curb this elongation. Randomized controlled trials (RCTs) have demonstrated that spectacle lenses with peripheral modifications, such as highly aspherical lenslets (HAL) or defocus incorporated multiple segments (DIMS), reduce myopia progression and axial elongation over 2 years. Similarly, multifocal contact lenses, especially those with high-add power (+ 2.50 D), have shown comparable reductions over 3 years. Safety is a critical consideration in myopia control. Multifocal spectacle lenses with peripheral plus designs are generally well tolerated, with only transient side effects, like dizziness and blurred vision. Soft multifocal contact lenses also exhibit a favorable safety profile, with low rates of serious adverse events. Thorough monitoring and reporting in these studies are essential to provide assurance about the safety of these interventions for children. Future research should aim to include more diverse populations in order to ensure the generalizability of findings across various demographic groups. Additionally, real-world data would offer valuable insights into the performance of these treatments in everyday scenarios. Observational studies, less influenced by industry sponsorship, could further validate these findings. Lastly, the clinical significance of the observed effects should be critically assessed to confirm that the reported benefits lead to meaningful reductions in myopia progression.},
}
@article {pmid39381228,
year = {2024},
author = {Hachem, M and Bermudez, JR and Ali, AH and Murtaza, FF and Rommala, M and Corridon, PR},
title = {Investigation of fatty acid profile of eyes recovered from slaughterhouse waste.},
journal = {Heliyon},
volume = {10},
number = {18},
pages = {e38148},
pmid = {39381228},
issn = {2405-8440},
abstract = {Polyunsaturated fatty acids (PUFAs), principally Docosahexaenoic acid (DHA, 22:6n-3), the foremost omega-3 PUFAs in the brain and eyes, have been implicated in maintaining the structural and functional properties of the retina and cornea. Another PUFA, Arachidonic Acid (AA, 20:4n-6), primary omega-6 PUFA in the cell membrane of phospholipids, is a central inflammatory mediator involved in many molecular and cellular functions under physiological and pathological conditions, including dry eye disease (DED) and age-related macular degeneration (AMD). This study investigated the fatty acids (FA) composition of the vitreous humor, retina, cornea, and whole eye in two mammals, the Arabian sheep (Ovis aries) and Arabian camel (Camelus dromedarius), with the aim of exploring new paths for beneficial PUFA production. In Ovis aries, the retina exhibited the highest content in DHA and AA with 4.30 ± 0.63 % and 13.48 ± 1.33 % of the total fatty acid content, respectively. In Camelus dromedarius, the DHA content was greater in the retina compared to all samples, and AA was detected in the vitreous humor, cornea, retina, and whole eye, with the highest content in the retina (15.38 ± 0.71 %). Comparing both mammals, the DHA fraction was higher in camel's retina than in sheep's retina, whereas no differences were noticed for AA accumulation. In conclusion, ocular tissues collected from agri-food waste in slaughterhouses could serve as a sustainable source for FA production and provide an innovative and emerging prospect in the nutrition, pharmaceutical, and healthcare sectors.},
}
@article {pmid39380913,
year = {2024},
author = {Matías-Pérez, D and Varapizuela-Sánchez, CF and Pérez-Campos, EL and González-González, S and Sánchez-Medina, MA and García-Montalvo, IA},
title = {Dietary sources of antioxidants and oxidative stress in age-related macular degeneration.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1442548},
pmid = {39380913},
issn = {1663-9812},
}
@article {pmid39380882,
year = {2025},
author = {Spaide, T and Rajesh, AE and Gim, N and Blazes, M and Lee, CS and Macivannan, N and Lee, G and Lewis, W and Salehi, A and de Sisternes, L and Herrera, G and Shen, M and Gregori, G and Rosenfeld, PJ and Pramil, V and Waheed, N and Wu, Y and Zhang, Q and Lee, AY},
title = {Estimating Uncertainty of Geographic Atrophy Segmentations with Bayesian Deep Learning.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100587},
pmid = {39380882},
issn = {2666-9145},
support = {R01 AG060942/AG/NIA NIH HHS/United States ; },
abstract = {PURPOSE: To apply methods for quantifying uncertainty of deep learning segmentation of geographic atrophy (GA).<br><br>DESIGN: Retrospective analysis of OCT images and model comparison.<br><br>PARTICIPANTS: One hundred twenty-six eyes from 87 participants with GA in the SWAGGER cohort of the Nonexudative Age-Related Macular Degeneration Imaged with Swept-Source OCT (SS-OCT) study.<br><br>METHODS: The manual segmentations of GA lesions were conducted on structural subretinal pigment epithelium en face images from the SS-OCT images. Models were developed for 2 approximate Bayesian deep learning techniques, Monte Carlo dropout and ensemble, to assess the uncertainty of GA semantic segmentation and compared to a traditional deep learning model.<br><br>MAIN OUTCOME MEASURES: Model performance (Dice score) was compared. Uncertainty was calculated using the formula for Shannon Entropy.<br><br>RESULTS: The output of both Bayesian technique models showed a greater number of pixels with high entropy than the standard model. Dice scores for the Monte Carlo dropout method (0.90, 95% confidence interval 0.87-0.93) and the ensemble method (0.88, 95% confidence interval 0.85-0.91) were significantly higher (P&#xa0;<&#xa0;0.001) than for the traditional model (0.82, 95% confidence interval 0.78-0.86).<br><br>CONCLUSIONS: Quantifying the uncertainty in a prediction of GA may improve trustworthiness of the models and aid clinicians in decision-making. The Bayesian deep learning techniques generated pixel-wise estimates of model uncertainty for segmentation, while also improving model performance compared with traditionally trained deep learning models.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39380780,
year = {2024},
author = {Labib, KM and Ghumman, H and Jain, S and Jarstad, JS},
title = {A Review of the Utility and Limitations of Artificial Intelligence in Retinal Disorders and Pediatric Ophthalmology.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71063},
pmid = {39380780},
issn = {2168-8184},
abstract = {Artificial intelligence (AI) is reshaping ophthalmology by enhancing diagnostic precision and treatment strategies, particularly in retinal disorders and pediatric ophthalmology. This review examines AI's efficacy in diagnosing conditions such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) using imaging techniques, such as optical coherence tomography (OCT) and fundus photography. AI also shows promise in pediatric care, aiding in the screening of retinopathy of prematurity (ROP) and the management of conditions, including pediatric cataracts and strabismus. However, the integration of AI in ophthalmology presents challenges, including ethical concerns regarding algorithm biases, privacy issues, and limitations in data set quality. Addressing these challenges is crucial to ensure AI's responsible and effective deployment in clinical settings. This review synthesizes current research, underscoring AI's transformative potential in ophthalmology while highlighting critical considerations for its ethical use and technological advancement.},
}
@article {pmid39379894,
year = {2024},
author = {Venkatesh, R and Joshi, A and Chitturi, SP and Choudhary, A and Prabhu, V and Bavaskar, S and Acharya, I and Mangla, R and Kathare, R and Yadav, NK and Chhablani, J},
title = {Role of fundus autofluorescence imaging in the management of submacular hemorrhage.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {440},
pmid = {39379894},
issn = {1471-2415},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Retinal Hemorrhage/diagnosis ; Aged ; Middle Aged ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Adult ; Aged, 80 and over ; Adolescent ; *Visual Acuity/physiology ; *Fundus Oculi ; Young Adult ; Optical Imaging/methods ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; },
abstract = {PURPOSE: To evaluate the baseline characteristics of fundus autofluorescence (FAF) in patients with submacular hemorrhage (SMH).<br><br>METHODS: This retrospective study included patients diagnosed with treatment-naive, foveal-involving subretinal hemorrhage (size&#x2009;>&#x2009;2-disc diameters) of any etiology, presenting between June 2017 and June 2023. Only cases with good-quality color fundus photographs, optical coherence tomography (OCT) scans, and blue-light FAF images at baseline were included. SMH imaging characteristics were documented and correlated with treatment outcomes. A successful treatment outcome was defined as the reduction, displacement or clearance of the SMH from beneath the fovea.<br><br>RESULTS: Nineteen cases of SMH (13 males, 6 females), ranging from 14 to 85 years, were analyzed. Neovascular age-related macular degeneration (nAMD) was the most common etiology (n&#x2009;=&#x2009;11, 58%). Baseline visual acuity ranged from 6/9 to counting fingers at &#xbd; meter, with a median presentation time of 7 days from symptom onset (range: 1-57 days). Treatment success was observed in 13 eyes (68%). Hypoautofluoroscence on FAF was significantly associated with SMH resolution (p&#x2009;=&#x2009;0.021). However, no association was found between treatment success and clinical hemorrhage characteristics (p&#x2009;=&#x2009;0.222), OCT findings (p&#x2009;=&#x2009;0.222), or specific treatments (p&#x2009;>&#x2009;0.05). Hypoautofluoroscence on FAF was the sole predictor of treatment success, as demonstrated by Spearman's correlation (r&#x2009;=&#x2009;0.637; p&#x2009;=&#x2009;0.003) and linear regression analysis (p&#x2009;=&#x2009;0.003).<br><br>CONCLUSION: FAF, in conjunction with color fundus photography and OCT, may provide valuable insights for clinicians in formulating treatment strategies for patients with SMH. Hypoautofluoroscence on FAF was a significant predictor of successful SMH resolution in this study.},
}
@article {pmid39379523,
year = {2025},
author = {Teo, KYC and Eldem, B and Joussen, A and Koh, A and Korobelnik, JF and Li, X and Loewenstein, A and Lövestam-Adrian, M and Navarro, R and Okada, AA and Pearce, I and Rodríguez, F and Wong, D and Wu, L and Zur, D and Zarranz-Ventura, J and Mitchell, P and Chaudhary, V and Lanzetta, P},
title = {Treatment regimens for optimising outcomes in patients with neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {39},
number = {5},
pages = {860-869},
pmid = {39379523},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Treatment Outcome ; Ranibizumab ; Practice Guidelines as Topic ; },
abstract = {Practice patterns for neovascular age-related macular degeneration (nAMD) have evolved from the landmark registration trials of vascular endothelial growth factor (VEGF) inhibitors. Non-monthly regimens like treat-and-extend (T&amp;E) have become popular due to their effectiveness in clinical practice. T&amp;E regimens attempt to limit the burden of visits and treatments by allowing progressively longer treatment intervals, but in so doing, are potentially associated with the expense of treating quiescent disease. This is acceptable to many patients and their ophthalmologists but can still be problematic in the real-world. Recent studies have further refined the T&amp;E approach by allowing for quicker and longer extension of treatment intervals when less severe disease is detected. With newer drugs offering increased durability, a shift to longer regular intervals may emerge as a new practice pattern for VEGF inhibitor therapy. This review aims to consolidate the current literature on the most effective treatment patterns and update treatment guidelines based on options that are now available. It also summarises new aspects of nAMD management that may help to further refine current practice.},
}
@article {pmid39379521,
year = {2025},
author = {Shirian, JD and Shukla, P and Singh, RP},
title = {Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues.},
journal = {Eye (London, England)},
volume = {39},
number = {1},
pages = {40-44},
pmid = {39379521},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Genetic Therapy/methods ; *Wet Macular Degeneration/therapy/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Choroidal Neovascularization/therapy ; *Macular Degeneration/therapy ; },
abstract = {Neovascular age-related macular degeneration (nAMD) can lead to significant vision impairment through the growth of abnormal neovascular membranes in the choroid. Despite advancements with current anti-vascular endothelial growth factor (VEGF) therapies, challenges such as frequent injections, inadequate response, and patient-related concerns persist. Emerging therapeutics aim to reduce vision-loss through a variety of mechanisms. Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951.},
}
@article {pmid39379520,
year = {2025},
author = {Wei, S and Li, J and Zhang, Y and Li, Y and Wang, Y},
title = {Ferroptosis in eye diseases: a systematic review.},
journal = {Eye (London, England)},
volume = {39},
number = {1},
pages = {18-27},
pmid = {39379520},
issn = {1476-5454},
mesh = {*Ferroptosis/physiology ; Humans ; *Eye Diseases/metabolism/pathology ; *Iron/metabolism ; },
abstract = {Ferroptosis is a type of iron-dependent cell death that differs from apoptosis, necroptosis, autophagy, and other forms of cell death. It is mainly characterized by the accumulation of intracellular lipid peroxides, redox imbalance, and reduced levels of glutathione and glutathione peroxidase 4. Studies have demonstrated that ferroptosis plays an important regulatory role in the occurrence and development of neurodegenerative diseases, stroke, traumatic brain injury, and ischemia-reperfusion injuries. Multiple mechanisms, such as iron metabolism, ferritinophagy, p53, and p62/Keap1/Nrf2, as well as the combination of FSP1/CoQ/NADPH and hepcidin/FPN-1 can alter the vulnerability to ferroptosis. Nevertheless, there has been limited research on the development and management of ferroptosis in the realm of eye disorders, with most studies focusing on retinal conditions such as age-related macular degeneration and retinitis pigmentosa. This review offers a thorough examination of the disruption of iron homeostasis in eye disorders, investigating the underlying mechanisms. We anticipate that the occurrence of ferroptotic cell death will not only establish a fresh field of study in eye diseases, but also present a promising therapeutic target for treating these diseases.},
}
@article {pmid39375139,
year = {2024},
author = {Zhang, Y and Jin, SS and Wang, J and Wang, NL},
title = {[An epidemiological survey of visual impairment in rural populations aged 30 and above: the Handan Eye Study].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {60},
number = {10},
pages = {813-821},
doi = {10.3760/cma.j.cn112142-20231021-00180},
pmid = {39375139},
issn = {0412-4081},
mesh = {Humans ; Prospective Studies ; *Rural Population/statistics &amp; numerical data ; Prevalence ; Male ; Female ; Middle Aged ; Adult ; Incidence ; *Blindness/epidemiology/etiology ; Aged ; *Cataract/epidemiology ; Glaucoma/epidemiology ; China/epidemiology ; Macular Degeneration/epidemiology ; Vision Disorders/epidemiology ; Vision, Low/epidemiology ; Myopia/epidemiology ; },
abstract = {Objective: To investigate the changes in prevalence and causes of blindness and visual impairment over six years among rural populations aged 30 and above in Yongnian County, Handan City, Hebei Province, a pilot area in northern China for blindness prevention and treatment, and to study the incidence of common blinding eye diseases. Methods: This population-based prospective cohort study included a baseline survey conducted from 2006 to 2007 using stratified cluster sampling, targeting 6 830 Han Chinese individuals aged 30 and above, with a response rate of 90.4%, and a follow-up survey conducted from 2012 to 2013 with 5 394 participants, maintaining a response rate of 85.3%. Visual impairment was defined according to World Health Organization standards as visual acuity<20/60 but ≥20/400, and blindness as visual acuity<20/400. Age-and gender-standardized prevalence rates of blindness and visual impairment, along with their 95% confidence intervals (CI), were estimated. The six-year incidence rates of primary glaucoma, age-related macular degeneration, and myopic maculopathy, along with their 95%CI, were reported. Results: At baseline, the standardized prevalence of bilateral blindness in individuals aged 30 and above was 0.6% (41/6 799) for presenting visual acuity and 0.5% (31/6 799) for best-corrected visual acuity. These rates were higher than those found in the follow-up survey, 0.5% (27/5 293) and 0.3% (17/5 276). Conversely, the standardized prevalence of bilateral visual impairment increased from 4.7% (361/6 799) and 1.0% (85/6 799) at baseline to 6.5% (355/5 293) and 1.4% (74/5 276) at follow-up, respectively. The leading cause of bilateral blindness was cataract in both baseline (13/31, 41.9%) and follow-up (7/17) surveys. Other major causes included myopic retinal degeneration (5/31, 16.1% at baseline; 2/17 at follow-up), glaucoma (3/31, 9.7% at baseline; 2/17 at follow-up), and corneal opacity (3/31, 9.7% at baseline; 2/17 at follow-up). Over six years, the incidence rates for primary glaucoma, early and late age-related macular degeneration, and myopic maculopathy in individuals aged 35 and above were 1.6% (95%CI: 1.2%-1.9%), 4.2% (95%CI: 3.8%-4.7%), 0.2% (95%CI: 0.2%-0.3%), and 0.1% (95%CI: 0.0%-0.2%), respectively. Conclusions: The prevalence of bilateral blindness in the rural population of Yongnian County, Handan City, Hebei Province, decreased over six years due to blindness prevention and treatment efforts but remained higher than in urban areas. Meanwhile, the prevalence of bilateral visual impairment increased since the baseline survey. Cataracts continued to be the primary cause of blindness, followed by myopic retinal degeneration, glaucoma, and corneal opacity.},
}
@article {pmid39374696,
year = {2025},
author = {Hoven, E and Michelet, JT and Vettore, MV and Lagali, N},
title = {Choroidal thickness after anti-vascular endothelial growth factor in typical neovascular age-related macular degeneration - A systematic review and meta-analysis.},
journal = {Survey of ophthalmology},
volume = {70},
number = {1},
pages = {86-95},
doi = {10.1016/j.survophthal.2024.09.011},
pmid = {39374696},
issn = {1879-3304},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Choroid/pathology/blood supply/diagnostic imaging ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Intravitreal Injections ; *Recombinant Fusion Proteins/therapeutic use ; Tomography, Optical Coherence/methods ; Ranibizumab/therapeutic use/administration &amp; dosage ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of blindness in the world and anti-vascular endothelial growth factor (VEGF) injections have been the standard of care for the wet/neovascular variant since 2004. Currently, there are conflicting reports regarding its effect on the choroid, which supplies outer retina with oxygen and other nutrients. We synthesize available information of anti-VEGF on choroidal thickness (CT) in treatment-naïve typical neovascular AMD patients during the initial 12-week loading phase. We found 43 studies involving 1901 eyes from 1878 patients were included. Meta-analysis of 35 studies reporting CT at baseline and after 12 weeks suggested a significant decrease in CT with anti-VEGF treatment. A greater mean change with aflibercept compared to ranibizumab was found in subgroup analyses of sub-foveal CT in types 1 and 2 macular neovascularization. The long-term consequences of reduced CT in neovascular AMD remain unclear and require further targeted studies.},
}
@article {pmid39373891,
year = {2024},
author = {Bijon, J and Hussain, MM and Bredefeld, CL and Boesze-Battaglia, K and Freund, KB and Curcio, CA},
title = {Abetalipoproteinemia with angioid streaks, choroidal neovascularization, atrophy, and extracellular deposits revealed by multimodal retinal imaging.},
journal = {Ophthalmic genetics},
volume = {45},
number = {6},
pages = {583-590},
pmid = {39373891},
issn = {1744-5094},
support = {P01 HL160470/HL/NHLBI NIH HHS/United States ; R01 EY006109/EY/NEI NIH HHS/United States ; R01 HL158054/HL/NHLBI NIH HHS/United States ; R21 EY032743/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroidal Neovascularization/genetics/diagnosis/pathology ; Female ; *Abetalipoproteinemia/genetics/diagnosis/pathology ; *Tomography, Optical Coherence ; *Angioid Streaks/genetics/diagnosis ; Aged ; Middle Aged ; *Multimodal Imaging ; Fluorescein Angiography ; Retinal Drusen/genetics/diagnosis/pathology ; Retinal Pigment Epithelium/pathology ; Atrophy ; Bruch Membrane/pathology ; },
abstract = {PURPOSE: Abetalipoproteinemia (ABL, MIM 200,100) is a rare autosomal recessive disorder caused by nonfunctional microsomal triglyceride transfer protein leading to absence of apolipoprotein B-containing lipoproteins in plasma and a retinitis pigmentosa-like fundus. The MTTP gene is expressed in retinal pigment epithelium (RPE) and ganglion cells of the human retina. Understanding ABL pathophysiology would benefit from new cellular-level clinical imaging of affected retinas.<br><br>METHODS: We report multimodal retinal imaging in two patients with ABL. Case 1 (67-year-old woman) exhibited a bilateral decline of vision due to choroidal neovascularization (CNV) associated with angioid streaks and calcified Bruch membrane. Optical coherence tomography were consistent with basal laminar deposits and subretinal drusenoid deposits (SDD).<br><br>RESULTS: Case 2 (46-year-old woman) exhibited unusual hyperpigmentation at the right fovea with count-fingers vision and a relatively unremarkable left fundus with 20/30 vision. The left eye exhibited the presence of nodular drusen and SDD and the absence of macular xanthophyll pigments.<br><br>CONCLUSION: We propose that mutated MTTP within the retina may contribute to ABL retinopathy in addition to systemic deficiencies of fat-soluble vitamins. This concept is supported by a new mouse model with RPE-specific MTTP deficiency and a retinal degeneration phenotype. The observed range of human pathology, including angioid streaks, underscores the need for continued monitoring in adulthood, especially for CNV, a treatable condition.},
}
@article {pmid39372715,
year = {2024},
author = {Iannucci, V and Bruscolini, A and Melchiorre, T and Lambiase, A and Mannocci, A},
title = {Reliability and reproducibility of an Italian questionnaire on "Knowledge of high social impact Eye Diseases" (KED-IT).},
journal = {PeerJ},
volume = {12},
number = {},
pages = {e17906},
pmid = {39372715},
issn = {2167-8359},
mesh = {Humans ; Italy/epidemiology ; Reproducibility of Results ; Surveys and Questionnaires ; Female ; Male ; Cross-Sectional Studies ; *Health Literacy ; Middle Aged ; *Eye Diseases/diagnosis ; *Health Knowledge, Attitudes, Practice ; Adult ; Aged ; },
abstract = {BACKGROUND: Health literacy plays an important role in public health. Although this has been demonstrated in the field of ophthalmology, there are very few specific instruments available to assess eye health literacy. This work aims to develop an Italian questionnaire on knowledge of eye diseases (Knowledge on Eye Disease, Italian version; KED-IT) and to evaluate its reliability and reproducibility. The KED-IT focuses on diseases with high social impact, specifically glaucoma, macular degeneration, diabetic retinopathy and keratoconus, which is the main cause of corneal transplant in Italy.<br><br>METHODS: A cross-sectional study was conducted. The KED-IT was self-administered by the study participants twice. The interval between each administration (T0 and T1) was 5 to 8 days. Reliability was assessed using the KR-20 coefficient. The test-retest Cohen's Kappa coefficient was estimated to measure the stability and reproducibility of the results obtained between T0 and T1.<br><br>RESULTS: A total of 60 subjects participated in the study. The response rate at T1 was 92%. The KR-20 reliability coefficient of the 14-item KED-IT questionnaire was good with a value of 0.878. The Cohen's kappa value for all 14 items of the KED-IT questionnaire was k&#xa0;=&#xa0;0.747, indicating good agreement.<br><br>CONCLUSIONS: The KED-IT is the first specific ophthalmic knowledge questionnaire validated in the Italian language and we hope that it may be a starting point for the study of eye health literacy in the Italian population.},
}
@article {pmid39371514,
year = {2024},
author = {Kim, DY and Hong, SM and Cho, JS and Lee, SB and Cho, HD},
title = {Inhibitory Effect of Phenolic Compounds on Vascular Endothelial Growth Factor-Induced Retinal Endothelial Permeability and Angiogenesis.},
journal = {Preventive nutrition and food science},
volume = {29},
number = {3},
pages = {321-331},
pmid = {39371514},
issn = {2287-1098},
abstract = {Age-related macular degeneration (AMD), often triggered by endothelial barrier disruption through vascular endothelial growth factor (VEGF), is a leading cause of blindness. This study investigated the inhibitory effects of phenolic compounds on VEGF-induced endothelial cell proliferation, migration, angiogenesis, and permeability using human retinal microvascular endothelial cells (hRECs). Thirty-seven polyphenolic compounds were selected from various databases based on their antioxidant properties, abundance in food, and solubility. These compounds significantly reduced migration, tube formation, and endothelial permeability in VEGF-stimulated hRECs. Notably, formononetin, eriodictyol, biochanin A, and p-coumaric acid were more effective in suppressing VEGF-induced angiogenesis and endothelial permeability than lutein. Molecular docking simulations revealed that formononetin, eriodictyol, and biochanin A had relatively lower binding energies with VEGF receptor 2 (VEGFR2) than lutein and sorafenib. These findings highlight the potential of phenolic compounds to be used as VEGFR2 inhibitors and an alternative strategy for preventing AMD.},
}
@article {pmid39371086,
year = {2024},
author = {Holste, G and Lin, M and Zhou, R and Wang, F and Liu, L and Yan, Q and Van Tassel, SH and Kovacs, K and Chew, EY and Lu, Z and Wang, Z and Peng, Y},
title = {Harnessing the power of longitudinal medical imaging for eye disease prognosis using Transformer-based sequence modeling.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {39371086},
issn = {2331-8422},
support = {R21 EY035296/EY/NEI NIH HHS/United States ; },
abstract = {Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classification approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing a disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA significantly outperformed a single-image baseline in 19/20 head-to-head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most influential, prior imaging still provides additional prognostic value.},
}
@article {pmid39369956,
year = {2025},
author = {Li, S and Qiu, Y and Li, Y and Wu, J and Yin, N and Ren, J and Shao, M and Yu, J and Song, Y and Sun, X and Gao, S and Cao, W},
title = {Serum metabolite biomarkers for the early diagnosis and monitoring of age-related macular degeneration.},
journal = {Journal of advanced research},
volume = {74},
number = {},
pages = {443-454},
pmid = {39369956},
issn = {2090-1224},
mesh = {Humans ; *Macular Degeneration/diagnosis/blood ; *Biomarkers/blood ; Male ; Female ; Aged ; Early Diagnosis ; Metabolomics/methods ; Middle Aged ; Machine Learning ; Disease Progression ; Aged, 80 and over ; Case-Control Studies ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible blindness worldwide, with significant challenges for early diagnosis and treatment.<br><br>OBJECTIVES: To identify new biomarkers that are important for the early diagnosis and monitoring of the severity/progression of AMD.<br><br>METHODS: We investigated the diagnostic and monitoring potential of blood metabolites in a cohort of 547 individuals (167 healthy controls, 240 individuals with other eye diseases as eye disease controls, and 140 individuals with AMD) from 2 centers over three phases: discovery phase 1, discovery phase 2, and an external validation phase. The samples were analyzed via a mass spectrometry-based, widely targeted metabolomic workflow. In discovery phases 1 and 2, we built a machine learning algorithm to predict the probability of AMD. In the external validation phase, we further confirmed the performance of the biomarker panel identified by the algorithm. We subsequently evaluated the performance of the identified biomarker panel in monitoring the progression and severity of AMD.<br><br>RESULTS: We developed a clinically specific three-metabolite panel (hypoxanthine, 2-furoylglycine, and 1-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine) via five machine learning models. The random forest model effectively discriminated patients with AMD from patents in the other two groups and showed acceptable calibration (area under the curve (AUC)&#xa0;=&#xa0;1.0; accuracy&#xa0;=&#xa0;1.0) in both discovery phases 1 and 2. An independent validation phase confirmed the diagnostic model's efficacy (AUC&#xa0;=&#xa0;0.962; accuracy&#xa0;=&#xa0;0.88). The three-biomarker panel model demonstrated an AUC of 1.0 in differentiating the severity of AMD via RF machine learning, which was consistent across both the discovery and external validation phases. Additionally, the biomarker concentrations remained stable under repeated freeze-thaw cycles (P&#xa0;>&#xa0;0.05).<br><br>CONCLUSIONS: This study reveals distinct metabolite variations in the serum of AMD patients, paving the way for the development of the first routine laboratory test for AMD.},
}
@article {pmid39369929,
year = {2025},
author = {Jiang, Y and Swain, T and Gim, N and Blazes, M and Donald, CM and Rokem, A and Owen, JP and Balu, N and Clark, ME and Goerdt, L and McGwin, G and Hunt, D and Curcio, CA and Levendovszky, SR and Trittschuh, EH and Owsley, C and Lee, CS},
title = {Outer Retinal Thinning is Associated With Brain Atrophy in Early Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {269},
number = {},
pages = {457-465},
pmid = {39369929},
issn = {1879-1891},
support = {OT2 OD032644/OD/NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Cross-Sectional Studies ; Male ; *Tomography, Optical Coherence/methods ; Aged ; *Magnetic Resonance Imaging ; *Atrophy ; Aged, 80 and over ; Brain/pathology/diagnostic imaging ; Retina/pathology/diagnostic imaging ; Macular Degeneration/diagnosis ; },
abstract = {PURPOSE: Both retinal changes and age-related macular degeneration (AMD) have been shown to be associated with Alzheimer's disease and related dementias (ADRD). In AMD, the outer retina is impacted significantly and early, but little is known about its association with cognition or changes in brain morphometry. This study investigates the relationship between retinal and brain morphometry in older adults with early and intermediate AMD.<br><br>DESIGN: Cross-sectional study.<br><br>METHODS: Adults &#x2265;70 years with normal, early, and intermediate AMD were recruited from Callahan Eye Hospital Clinics at the University of Alabama at Birmingham. Participants underwent cognitive testing, optical coherence tomography, and magnetic resonance imaging. Associations of retinal layer thickness with brain volume and thickness of specific brain regions were evaluated utilizing multivariable linear regression. The relevance of retinal thickness variables in brain volumetrics was quantified using least absolute shrinkage and selection operator regression models. Correlations between demographic variables, cognitive scores, and brain morphometry were evaluated.<br><br>RESULTS: Participants with thinner outer retina had significantly smaller hippocampus (&#x3b2; = 0.019, P = .022), lower occipital cortex regions of interest (occipital ROIs) thickness (&#x3b2; = 5.68, P = .020), and lower cortical thickness in ADRD-related brain regions (&#x3b2; = 7.72, P = .006). People with thinner total retina had significantly lower occipital ROIs (&#x3b2; = 3.19, P = .009) and ADRD-related brain region (&#x3b2; = 3.94, P = .005) thickness. Outer retinal thickness in the outer Early Treatment of Diabetic Retinopathy Study ring was the most frequently reported retinal variable associated with brain morphometry on least absolute shrinkage and selection operator regression. Total gray matter volume showed positive correlations with education (Pearson's r = 0.30, P = .022).<br><br>CONCLUSIONS: In older adults with normal retinal aging and early and intermediate AMD, thinner outer retina had specific associations with brain regions primarily involved in vision and cognition, such as lower hippocampal volume and lower thickness of the occipital ROIs and brain regions known to show early structural changes in dementia.},
}
@article {pmid39369799,
year = {2024},
author = {Rahmati, M and Smith, L and Lee, H and Boyer, L and Fond, G and Yon, DK and Lee, H and Soysal, P and Udeh, R and Dolja-Gore, X and McEVoy, M and Piyasena, MP and Pardhan, S},
title = {Associations between vision impairment and eye diseases with dementia, dementia subtypes and cognitive impairment: An umbrella review.},
journal = {Ageing research reviews},
volume = {101},
number = {},
pages = {102523},
doi = {10.1016/j.arr.2024.102523},
pmid = {39369799},
issn = {1872-9649},
mesh = {Humans ; *Dementia/epidemiology/etiology ; *Cognitive Dysfunction/epidemiology/etiology ; *Vision Disorders/epidemiology ; *Eye Diseases/epidemiology/complications ; },
abstract = {Vision impairment (VI) and eye diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataract have been reported to be associated with cognitive impairment and dementia, however, to date, very little attempt has been made to collate and synthesizes such literature. Therefore, the aim of this umbrella review is to systematically assesses the credibility and certainty of evidence of associations between vision impairment (VI) and eye diseases with cognitive impairment, dementia and dementia subtypes. We conducted an umbrella review of meta-analyses by screening articles in any language in PubMed, MEDLINE (Ovid), EMBASE, Web of Science, Cochrane CENTRAL and CDSR published from database inception up to May 30, 2024. Quality appraisal of each included original meta-analysis was assessed using A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2). The certainty of the evidence was based on statistical significance, study size, heterogeneity, small study effects, prediction intervals (PI), and bias. We followed an a-priori protocol registered with PROSPERO (CRD42024564249). We identified 13 meta-analyses (AMSTAR 2; high accuracy of the findings 1, moderate 10, and low 2) that included 232 original articles based on 99,337,354 participants. Overall, no evidence was highly suggestive or convincing. Suggestive evidence was found for associations between cataract and dementia (equivalent odds ratio [eOR] 1.20, 95 %CI, 1.16-1.25), cataract and Alzheimer's disease (eOR 1.21, 95 %CI, 1.15-1.28), and AMD and Alzheimer's disease (eOR 1.27, 95 %CI, 1.27-1.27). Weak evidence was found for associations between VI and dementia (eOR 1.50, 95 %CI, 1.23-1.84), DR and dementia (eOR 1.33, 95 %CI, 1.17-1.50), cataract and vascular dementia (eOR 1.26, 95 %CI, 1.09-1.45), VI identified by cross-sectional studies and cognitive impairment (eOR 2.37, 95 %CI, 2.31-2.44), and VI identified by objective measures and cognitive impairment (eOR 1.56, 95 %CI, 1.12-2.18). The observed suggestive level of evidence for the relationship between eye disease and dementia (as well as dementia subtypes) suggests that policy and interventions to aid in the prevention and management of eye disease may also aid in the prevention of dementia syndrome. Where the level of evidence is weak, further studies are needed with stronger methodological approaches.},
}
@article {pmid39369033,
year = {2024},
author = {Dong, Y and Qian, C and Yan, P and Wan, G},
title = {YTHDF1-regulated ALOX5 in retinal pigment epithelial cells under hypoxia enhances VEGF expression and promotes viability, migration, and angiogenesis of vascular endothelial cells.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {23226},
pmid = {39369033},
issn = {2045-2322},
support = {No.202300410412//Natural Science Foundation of Henan Province Youth Science Foundation Project/ ; No.LHGJ20190228//Medical Science and Technology Project of Henan Province/ ; },
mesh = {Humans ; *Cell Movement/genetics ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; *Cell Survival/genetics ; *Retinal Pigment Epithelium/metabolism ; *Arachidonate 5-Lipoxygenase/metabolism/genetics ; *RNA-Binding Proteins/metabolism/genetics ; Cell Line ; Cell Hypoxia ; Neovascularization, Pathologic/metabolism/genetics ; Endothelial Cells/metabolism ; Neovascularization, Physiologic/genetics ; Animals ; Gene Expression Regulation ; Macular Degeneration/metabolism/genetics/pathology ; Epithelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Angiogenesis ; },
abstract = {Upregulation of vascular endothelial growth factor (VEGF) and enhanced angiogenesis have been implicated in the severe progression of age-related macular degeneration (AMD). Abnormal arachidonate 5-lipoxygenase (ALOX5) is associated with AMD pathogenesis. However, no reports have shown the causal role of ALOX5 in angiogenesis during AMD. In the present study, ARPE-19 cells were exposed to hypoxia, an inducer of VEGF expression. Potential proteins implicated in AMD progression were predicted using bioinformatics. RNA affinity antisense purification-mass spectrometry (RAP-MS) was applied to identify the binding proteins of ALOX5 3'UTR. Expression of ALOX5 and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1) was detected by qRT-PCR and western blotting. VEGF expression and secretion were assessed by immunofluorescence and ELISA, respectively. The chicken embryo chorioallantoic membrane (CAM) was used to analyze the effect of ALOX5 on angiogenesis. RNA stability was assayed using the Actinomycin D assay. The results show that hypoxia promoted cell growth and increased VEGF expression in ARPE-19 cells. ALOX5 was associated with AMD progression, and hypoxia upregulated ALOX5 expression in ARPE-19 cells. ALOX5 silencing reduced VEGF expression induced by hypoxia in ARPE-19 cells. Moreover, the conditioned medium of ALOX5-silenced ARPE-19 cells could suppress the viability and migration of HUVECs and diminish angiogenesis in the CAM. Furthermore, YTHDF1 was validated to bind to ALOX5 3'UTR, and YTHDF1 promoted ALOX5 expression by elevating the stability of ALOX5 mRNA. In conclusion, our findings demonstrate that YTHDF1-regulated ALOX5 increases VEGF expression in hypoxia-exposed ARPE-19 cells and enhances the viability, migration, and angiogenesis of vascular endothelial cells.},
}
@article {pmid39368749,
year = {2025},
author = {Simon, LS and Davis, ML and Medunjanin, D and Fanning, L and Damonte, JC and Hunt, K and Maa, AY},
title = {National Experience of Technology-based Eye Care Services: A Comprehensive Ophthalmology Telemedicine Initiative.},
journal = {Ophthalmology},
volume = {132},
number = {4},
pages = {442-451},
pmid = {39368749},
issn = {1549-4713},
support = {VA999999/ImVA/Intramural VA/United States ; },
mesh = {Humans ; Female ; *Telemedicine/organization &amp; administration ; Male ; Middle Aged ; *Ophthalmology/organization &amp; administration ; Aged ; United States/epidemiology ; United States Department of Veterans Affairs ; Veterans ; *Eye Diseases/epidemiology/therapy/diagnosis ; Rural Population/statistics &amp; numerical data ; Prevalence ; Aged, 80 and over ; Adult ; },
abstract = {PURPOSE: Technology-based Eye Care Services (TECS) is a tele-ophthalmology program operating in the Veterans' Health Administration since 2015. This study explores characteristics of the national TECS population, evaluates implementation and sustainability of TECS, and analyzes possible associations and effects of demographic characteristics and social determinants of health on being diagnosed with a vision-threatening (VT) disease.<br><br>DESIGN: Implementation and sustainability of TECS from 2015 to 2022 were examined along with the sociodemographic characteristics of veterans served through TECS in&#xa0;2021.<br><br>PARTICIPANTS: Veteran patients seen in TECS nationwide.<br><br>MAIN OUTCOME MEASURES: Characteristics, disease prevalence and diagnoses, implementation success rate, sustainability rate, and preliminary analysis of outcomes and disparity.<br><br>METHODS: Per quarter from 2015 to 2022, TECS sites were classified as implementing, active, or sustained. Standard query language was used to determine sociodemographic data, and logistic regression models were used to identify risk factors associated with VT eye diagnosis.<br><br>RESULTS: A total of 21 712 Veterans, 52.1% rural or highly rural, were served by TECS in 2021. The average age was 64.7 years, with women comprising 10.9% of the population served. From 2015 to 2022, of the 67 TECS sites initiated, 6 were implementing with 51 of 61 initiated sites still operational in the first quarter (Q1) of 2022 (83.6% success rate). Age-related macular degeneration (AMD) and cataracts were more prevalent in rural and highly rural populations (7.6% and 11.3%, and 48.8% and 55.0%, respectively) versus urban populations (5.8% and 47.8%); glaucoma and diabetic retinopathy (DR) had the opposite association. The prevalence of any type of VT eye disease was lowest in the Mountains/Central region (0.54%) and highest in the Southeast region (3.2%) of the United States. Rural and highly rural residents were 1.3 and 2.5 times as likely, respectively, to be diagnosed with a VT eye disease than urban residents.<br><br>CONCLUSIONS: Implementation and sustainability of TECS have been promising. The data provide key information that can be used to improve the deployment of TECS and similar programs, along with the possible future direction of TECS. Moreover, experience from one national ocular telehealth program clearly illustrates that telemedicine can address eye care disparities in the Veteran population and may be used for other vulnerable groups as well.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39368694,
year = {2024},
author = {Beqiri, S and Herrera, G and Liu, J and Shen, M and Berni, A and El-Mulki, OS and Cheng, Y and Trivizki, O and Kastner, J and O'Brien, RC and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Evaluating the persistence of large choroidal hypertransmission defects using SS-OCT imaging.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110117},
pmid = {39368694},
issn = {1096-0007},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/pathology/diagnostic imaging ; Male ; Aged ; Female ; Prospective Studies ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Disease Progression ; Aged, 80 and over ; Fluorescein Angiography/methods ; Visual Acuity/physiology ; Middle Aged ; Follow-Up Studies ; Macular Degeneration/diagnostic imaging ; },
abstract = {In age-related macular degeneration (AMD), large choroidal hypertransmission defects (hyperTDs) are identified on en face optical coherence tomography (OCT) images as bright lesions measuring at least 250 μm in greatest linear dimension (GLD). These choroidal hyperTDs arise from focal attenuation or loss of the retinal pigment epithelium (RPE). We previously reported that once large hyperTDs formed, they were likely to persist compared with smaller lesions that were more likely to be transient. Due to their relative persistence, these large persistent choroidal hyperTDs are a point-of-no-return in the progression of intermediate AMD to the late stage of atrophic AMD. Moreover, the onset of these large choroidal hyperTDs can serve as a clinical trial endpoint when studying therapies that might slow disease progression from intermediate AMD to late atrophic AMD. To confirm the persistence of these large choroidal hyperTDs, we studied an independent dataset of AMD eyes enrolled in an ongoing prospective swept-source OCT (SS-OCT) natural history study to determine their overall persistence. We identified a total of 202 eyes with large choroidal hyperTDs containing 1725 hyperTDs followed for an average of 46.6 months. Of the 1725 large hyperTDs, we found that 1718 (99.6%) persisted while only 7 hyperTDs (0.4%) were non-persistent. Of the 7 non-persistent large hyperTDs in 6 eyes, their average GLD at baseline was 385 μm. Of the large hyperTDs ranging in size between 250 and 300 μm when first detected, only one was not persistent with a baseline GLD of 283 μm. In 6 of the non-persistent hyperTDs, the loss of a detectable large hyperTD was due to the accumulation of hyperreflective material along the retinal pigment epithelium (RPE) and in the retina over the area where the hyperTD was located. This hyperreflective material is thought to represent the migration and aggregation of RPE cells into this focal region where the choroidal hyperTD arose due to attenuated or lost RPE.},
}
@article {pmid39367441,
year = {2024},
author = {Sha, L and Zhao, Y and Li, S and Wei, D and Tao, Y and Wang, Y},
title = {Insights to Ang/Tie signaling pathway: another rosy dawn for treating retinal and choroidal vascular diseases.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {898},
pmid = {39367441},
issn = {1479-5876},
support = {20JCZD001 and 21JCZD002//Basic Research Project of Henan Eye Institute/ ; 221100310200//Science and Technology Major Project of Henan Province/ ; 224200510013//Zhongyuan Science and Technology Leading Talent Project/ ; },
mesh = {Humans ; *Signal Transduction ; Animals ; Retinal Diseases/metabolism/drug therapy/pathology ; Vascular Diseases/metabolism/drug therapy ; Receptors, TIE/metabolism ; Choroid/pathology/metabolism ; },
abstract = {Retinal neurovascular unit (NVU) is a multi-cellular structure that consists of the functional coupling between neural tissue and vascular system. Disrupted NVU will result in the occurrence of retinal and choroidal vascular diseases, which are characterized by the development of neovascularization, increased vascular permeability, and inflammation. This pathological entity mainly includes neovascular age-related macular degeneration (neovascular-AMD), diabetic retinopathy (DR) retinal vein occlusion (RVO), and retinopathy of prematurity (ROP). Emerging evidences suggest that the angopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (Ang/Tie) signaling pathway is essential for the development of retinal and choroidal vascular. Tie receptors and their downstream pathways play a key role in modulating the vascular development, vascular stability, remodeling and angiogenesis. Angiopoietin 1 (Ang1) is a natural agonist of Tie2 receptor, which can promote vascular stability. On the other hand, angiopoietin 2 (Ang2) is an antagonist of Tie2 receptor that causes vascular instability. Currently, agents targeting the Ang/Tie signaling pathway have been used to inhibit neovascularization and vascular leakage in neovascular-AMD and DR animal models. Particularly, the AKB-9778 and Faricimab have shown promising efficacy in improving visual acuity in patients with neovascular-AMD and DR. These experimental and clinical evidences suggest that activation of Ang/Tie signaling pathway can inhibit the vascular permeability, neovascularization, thereby maintaining the normal function and structure of NVU. This review seeks to introduce the versatile functions and elucidate the modulatory mechanisms of Ang/Tie signaling pathway. Recent pharmacologic therapies targeting this pathway are also elaborated and summarized. Further translation of these findings may afford a new therapeutic strategy from bench to bedside.},
}
@article {pmid39367169,
year = {2025},
author = {Subrahmanian, SM and Yerlikaya, EI and Sunilkumar, S and Toro, AL and McCurry, CM and Grillo, SL and Barber, AJ and Sundstrom, JM and Dennis, MD},
title = {Deletion of the stress response protein REDD1 prevents sodium iodate-induced RPE damage and photoreceptor loss.},
journal = {GeroScience},
volume = {47},
number = {2},
pages = {1789-1803},
pmid = {39367169},
issn = {2509-2723},
support = {R01 EY029702/EY/NEI NIH HHS/United States ; R01 EY032879/EY/NEI NIH HHS/United States ; R21 EY035844/EY/NEI NIH HHS/United States ; M2024006F//BrightFocus Foundation/ ; R21 EY035844/EY/NEI NIH HHS/United States ; R01 EY029702/EY/NEI NIH HHS/United States ; R01 EY032879/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Iodates/toxicity ; Mice ; *Transcription Factors/genetics/metabolism ; Disease Models, Animal ; Reactive Oxygen Species/metabolism ; *Macular Degeneration/chemically induced/genetics/metabolism/pathology ; Mice, Knockout ; Mice, Inbred C57BL ; Oxidative Stress ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in elderly populations, yet the molecular events that initiate the early retinal defects that lead to visual function deficits remain poorly understood. The studies here explored a role for the stress response protein Regulated in Development and DNA damage response 1 (REDD1) in the development of retinal pathology by using the oxidant stressor sodium iodate (NaIO3) to model dry AMD in mice. REDD1 protein abundance was increased in the retinal pigmented epithelium (RPE) and retina of mice administered NaIO3. In wild-type REDD1[+/+] mice, reactive oxygen species (ROS) levels were robustly increased in the outer retinal layers 1 day after NaIO3 administration, with focal areas of increased ROS seen throughout the outer retina after 7 days. In contrast with REDD1[+/+] mice, ROS levels were blunted in REDD1[-/-] mice after NaIO3 administration. REDD1 was also required for upregulated expression of pro-inflammatory factors in the RPE/retina and immune cell activation in the outer retina following NaIO3 administration. In REDD1[+/+] mice, NaIO3 reduced RPE65 and rhodopsin levels in the RPE and photoreceptor layers, respectively. Unlike REDD1[+/+] mice, REDD1[-/-] mice did not exhibit disrupted RPE integrity, retinal degeneration, or photoreceptor thinning. Overall, REDD1 deletion was sufficient to prevent retinal oxidative stress, RPE damage, immune cell activation, and photoreceptor loss in response to NaIO3. The findings support a potential role for REDD1 in the development of retinal complications in the context of dry AMD.},
}
@article {pmid39365260,
year = {2024},
author = {Cheung, R and Trinh, M and Nivison-Smith, L},
title = {Retinal Pigment Epithelium Curvature Can Predict Late Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {12},
pages = {7},
pmid = {39365260},
issn = {1552-5783},
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Female ; Male ; Aged ; *Macular Degeneration/diagnosis ; Aged, 80 and over ; *Disease Progression ; *Bruch Membrane/pathology ; *Tomography, Optical Coherence/methods ; Follow-Up Studies ; Prognosis ; Retinal Drusen/diagnosis ; Middle Aged ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: Outer retinal band integrity strongly predicts late age-related macular degeneration (AMD). However, it is often assessed subjectively as "continuity" using inconsistent definitions. Alternatively, "curvature" of the outer retinal bands is a quantitative metric that strongly correlates with AMD biomarkers and can screen for intermediate AMD. We evaluated the prognostic ability of retinal pigment epithelium (RPE) and ellipsoid zone (EZ) curvature for late AMD against outer retinal band continuity, pigmentary abnormalities, reticular pseudodrusen, and drusen volume.<br><br>METHODS: Consecutive patients with intermediate AMD who progressed to late AMD (n = 17) or remained stable (n = 42) were recruited. RPE and EZ curvature were quantified as a ratio of their lengths over Bruch's membrane using the sinuosity method of assessing river curvature, where a ratio of &#x223c;1 indicates no outer retinal pathology. RPE, EZ, and Bruch's membrane were manually segmented and their lengths automatically extracted. The primary outcomes were outer retinal sinuosity and the odds ratio of predicting late AMD.<br><br>RESULTS: Mean follow-up time for progressors and nonprogressors was 4.4 and 3.6 years. RPE sinuosity was strongly associated with pigmentary abnormalities (P = 0.001) and drusen volume (P = 0.004) but not reticular pseudodrusen (P = 0.28). RPE sinuosity >1.03 was the strongest predictor of late AMD developing within 5 years (15 [2.9-75]) and across the study period (25 [2.3-282]). Drusen volume >0.03 mm3 was the strongest predictor of progression within 2 years (33 [2.5-426]), and RPD could not independently predict progression within any time frame.<br><br>CONCLUSIONS: RPE curvature is a promising, quantitative outer retinal biomarker that can prognosticate late AMD and potentially enhance prognostic models.},
}
@article {pmid39363330,
year = {2024},
author = {Du, X and Park, J and Zhao, R and Smith, RT and Koronyo, Y and Koronyo-Hamaoui, M and Gao, L},
title = {Hyperspectral retinal imaging in Alzheimer's disease and age-related macular degeneration: a review.},
journal = {Acta neuropathologica communications},
volume = {12},
number = {1},
pages = {157},
pmid = {39363330},
issn = {2051-5960},
support = {R01HL165318/HL/NHLBI NIH HHS/United States ; R01AG056478/AG/NIA NIH HHS/United States ; R01EY029397/EY/NEI NIH HHS/United States ; RF1NS128488/NS/NINDS NIH HHS/United States ; R01 AG056478/AG/NIA NIH HHS/United States ; R01 AG055865/AG/NIA NIH HHS/United States ; R01 HL165318/HL/NHLBI NIH HHS/United States ; RF1 NS128488/NS/NINDS NIH HHS/United States ; R01 EY029397/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/pathology ; *Retina/diagnostic imaging/pathology ; *Macular Degeneration/diagnostic imaging/pathology ; Hyperspectral Imaging/methods ; Animals ; },
abstract = {While Alzheimer's disease and other neurodegenerative diseases have traditionally been viewed as brain disorders, there is growing evidence indicating their manifestation in the eyes as well. The retina, being a developmental extension of the brain, represents the only part of the central nervous system that can be noninvasively imaged at a high spatial resolution. The discovery of the specific pathological hallmarks of Alzheimer's disease in the retina of patients holds great promise for disease diagnosis and monitoring, particularly in the early stages where disease progression can potentially be slowed. Among various retinal imaging methods, hyperspectral imaging has garnered significant attention in this field. It offers a label-free approach to detect disease biomarkers, making it especially valuable for large-scale population screening efforts. In this review, we discuss recent advances in the field and outline the current bottlenecks and enabling technologies that could propel this field toward clinical translation.},
}
@article {pmid39362220,
year = {2024},
author = {Dalvi, S and Roll, M and Chatterjee, A and Kumar, LK and Bhogavalli, A and Foley, N and Arduino, C and Spencer, W and Reuben-Thomas, C and Ortolan, D and Pébay, A and Bharti, K and Anand-Apte, B and Singh, R},
title = {Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.},
journal = {Developmental cell},
volume = {59},
number = {24},
pages = {3290-3305.e9},
pmid = {39362220},
issn = {1878-1551},
support = {R01 EY030183/EY/NEI NIH HHS/United States ; R01 EY033192/EY/NEI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; R01 EY027083/EY/NEI NIH HHS/United States ; S10 OD030302/OD/NIH HHS/United States ; R21 EY030817/EY/NEI NIH HHS/United States ; R01 EY028167/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Matrix Metalloproteinase 2/metabolism ; Retinal Drusen/metabolism/pathology ; Receptor for Advanced Glycation End Products/metabolism ; Models, Biological ; Male ; Aged ; },
abstract = {Age-related macular degeneration (AMD) and related macular dystrophies (MDs) primarily affect the retinal pigment epithelium (RPE) in the eye. A hallmark of AMD/MDs that drives later-stage pathologies is drusen. Drusen are sub-RPE lipid-protein-rich extracellular deposits, but how drusen forms and accumulates is not known. We utilized human induced pluripotent stem cell (iPSC)-derived RPE from patients with AMD and three distinct MDs to demonstrate that reduced activity of RPE-secreted matrix metalloproteinase 2 (MMP2) contributes to drusen in multiple maculopathies in a genotype-agnostic manner by instigating sterile inflammation and impaired lipid homeostasis via damage-associated molecular pattern molecule (DAMP)-mediated activation of receptor for advanced glycation end-products (RAGE) and increased secretory phospholipase 2-IIA (sPLA2-IIA) levels. Therapeutically, RPE-specific MMP2 supplementation, RAGE-antagonistic peptide, and a small molecule inhibitor of sPLA2-IIA ameliorated drusen accumulation in AMD/MD iPSC-RPE. Ultimately, this study defines a causal role of the MMP2-DAMP-RAGE-sPLA2-IIA axis in AMD/MDs.},
}
@article {pmid39362194,
year = {2024},
author = {Nichani, PAH and Popovic, MM and Mihalache, A and Pathak, A and Muni, RH and Wong, DTW and Kertes, PJ},
title = {Efficacy and Safety of Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Retinal Vein Occlusion: A Meta-Analysis.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {5-6},
pages = {355-372},
pmid = {39362194},
issn = {1423-0267},
mesh = {Humans ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Macular Edema/drug therapy/diagnosis/etiology ; *Visual Acuity ; *Retinal Vein Occlusion/drug therapy/diagnosis/complications ; *Diabetic Retinopathy/drug therapy/diagnosis ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; },
abstract = {INTRODUCTION: Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has become the mainstay of treatment in many retinal diseases. The comparative efficacy and safety of newer bispecific anti-VEGF/angiopoietin 2 (Ang2) agents in the treatment paradigm versus widely used monospecific anti-VEGF agents remains unclear.<br><br>METHODS: A systematic literature search of MEDLINE, Embase, and Cochrane Library was conducted to identify comparative observational studies and randomized controlled trials published from 2015 to Jul 2024. With assessment by three independent reviewers, original English peer-reviewed full-text articles evaluating faricimab versus monospecific anti-VEGF agent(s) in FDA-indicated retinal disease with data on at least one set of efficacy and/or safety outcomes for each treatment arm and a minimum 3-month follow-up period were included. Data were appraised using the Cochrane RoB2 and ROBINS-I tools, PRISMA, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines. All outcomes were collected at the last follow-up. Random effects meta-analyses with 95% confidence intervals were conducted to calculate weighted mean differences and risk ratios. Change in best-corrected visual acuity (BCVA, ETDRS letters), change in central subfield thickness (CSFT, &#x3bc;m), and presence of retinal fluid were primary endpoints; ocular adverse events were secondary endpoints.<br><br>RESULTS: Across 13 studies, in the context of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), 2,226 eyes received anti-VEGF monotherapy and 3,022 received faricimab. Final and change in BCVA were similar between treatment groups. Faricimab was associated with a significantly higher reduction in CSFT in DME and RVO eyes but not in nAMD eyes. The incidence of ocular adverse events was similar between groups.<br><br>CONCLUSION: There was no difference in BCVA between faricimab and anti-VEGF monotherapy in nAMD, DME, and RVO. While faricimab offered superior improvement in CSFT at the final follow-up for DME and RVO eyes, this effect was not seen in nAMD eyes. Future studies are needed to establish the long-term safety and efficacy of faricimab for retinal vascular disease.},
}
@article {pmid39361587,
year = {2024},
author = {Lee, YJ and Kang, S and Won, JY and Roh, YJ and Ra, H and Lee, MY and Park, SP and Jee, DH},
title = {Real-world visual acuity outcomes for patients with naïve neovascular age-related macular degeneration treated with aflibercept, ranibizumab, or bevacizumab in the Republic of Korea.},
journal = {PloS one},
volume = {19},
number = {10},
pages = {e0310381},
pmid = {39361587},
issn = {1932-6203},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Female ; Male ; *Bevacizumab/therapeutic use/administration &amp; dosage ; *Visual Acuity/drug effects ; Republic of Korea ; Aged ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Treatment Outcome ; Aged, 80 and over ; Macular Degeneration/drug therapy ; Intravitreal Injections ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; },
abstract = {BACKGROUND: To compare the visual outcomes of different anti-vascular endothelial growth factor (VEGF) drugs, including aflibercept, ranibizumab, and bevacizumab, in a real-world setting in Korea.<br><br>METHODS: We collected data from patients who received monotherapy using one of these three anti-VEGF drugs as na&#xef;ve treatment after being diagnosed with neovascular age-related macular degeneration. The number of injections and visual acuity (VA) outcomes of each cohort were obtained and pairwise comparisons were performed using propensity score matching.<br><br>RESULTS: A total of 254 aflibercept, 238 ranibizumab, and 282 bevacizumab treatment-na&#xef;ve eyes were included. The mean VA change at 3 years for all cohorts combined was -1.8 letters, and the mean number of injections was 9.4. In the direct comparison of the three drugs, the mean change in the VA letter score was +2.0 letters for aflibercept and -11.7 letters for bevacizumab (P < 0.001). The number of aflibercept injections was significantly higher than the number of bevacizumab injections (P = 0.002). The visual outcomes for aflibercept and ranibizumab were +4.7 letters and -1.9 letters, respectively, and comparable results were obtained (P = 0.13). The VA outcomes for ranibizumab and bevacizumab were also not significantly different (P = 0.09). The numbers of injections for aflibercept, ranibizumab, and bevacizumab were 10.8, 6.7, and 8.8, respectively. Significant differences were observed between the injection frequencies comparisons of aflibercept and ranibizumab and ranibizumab and bevacizumab (P < 0.001 and P = 0.002, respectively).<br><br>CONCLUSIONS: In the Korean clinical medical environment, which included various confounding factors, especially socioeconomic ones, the aflibercept VA outcome was significantly better than that of bevacizumab, and aflibercept injections were the most numerous. These real-world data imply that the drug effect as well as the environment in which the drug can be sufficiently used affected patient final VA scores.},
}
@article {pmid39360955,
year = {2024},
author = {Sayed, A and Ravichandran, P and Canizela, C and Hussain, RM},
title = {Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials.},
journal = {Therapeutic delivery},
volume = {15},
number = {11},
pages = {829-843},
pmid = {39360955},
issn = {2041-6008},
mesh = {Humans ; *Diabetic Retinopathy/drug therapy ; *Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/administration &amp; dosage ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase I as Topic ; Macular Edema/drug therapy/etiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Drug Delivery Systems/methods ; },
abstract = {EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.},
}
@article {pmid39359698,
year = {2024},
author = {Wei, Q and Tu, X and Qiu, Q and Wang, L},
title = {Untargeted Metabolomic Study of Patients with Wet Age-Related Macular Degeneration in Aqueous Humor.},
journal = {Clinical interventions in aging},
volume = {19},
number = {},
pages = {1571-1580},
pmid = {39359698},
issn = {1178-1998},
mesh = {Humans ; *Aqueous Humor/metabolism ; Male ; *Metabolomics ; Female ; Aged ; *Biomarkers/metabolism ; *Tandem Mass Spectrometry ; Chromatography, Liquid ; *Wet Macular Degeneration/metabolism ; Aged, 80 and over ; Case-Control Studies ; Middle Aged ; },
abstract = {PURPOSE: The objective of this study was to ascertain metabolic biomarkers and investigate the metabolic alterations associated with aqueous humor (AH) in wet age-related macular degeneration (AMD).<br><br>METHODS: AH samples were collected from a total of 20 participants, including 10 individuals diagnosed with wet AMD and 10 individuals undergoing cataract surgery, serving as the control group. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify and quantify metabolites.<br><br>RESULTS: A total of 155 metabolites were identified in the AH samples. Among them, 10 metabolites emerged as potential biomarkers capable of differentiating patients with wet AMD from the control group. In the AH of wet AMD patients, there was increased expression of Cardiolipin (CL) (72:5), Diglyceride (DG) (18:3_18:2), DG (36:5e) and Triglyceride (TG) (24:7), while the expression of Ceramides (Cer) (d32:0), Cer (d34:0), Cer (d36:0), Monogalactosyldiacylglycerol (MGDG) (16:1_18:3), Sphingosine (SPH) (d18:0) and TG (16:0_10:4_16:0) was down regulated.<br><br>CONCLUSION: Through metabolomics analysis of AH, this study successfully uncovered valuable metabolic biomarkers linked to wet AMD. These findings contribute to a more comprehensive understanding of the pathogenesis of wet AMD and offer potential avenues for the development of innovative treatment strategies for this condition.},
}
@article {pmid39359529,
year = {2024},
author = {Hashemian, H and Peto, T and Ambrósio, R and Lengyel, I and Kafieh, R and Muhammed Noori, A and Khorrami-Nejad, M},
title = {Application of Artificial Intelligence in Ophthalmology: An Updated Comprehensive Review.},
journal = {Journal of ophthalmic &amp; vision research},
volume = {19},
number = {3},
pages = {354-367},
pmid = {39359529},
issn = {2008-2010},
abstract = {Artificial intelligence (AI) holds immense promise for transforming ophthalmic care through automated screening, precision diagnostics, and optimized treatment planning. This paper reviews recent advances and challenges in applying AI techniques such as machine learning and deep learning to major eye diseases. In diabetic retinopathy, AI algorithms analyze retinal images to accurately identify lesions, which helps clinicians in ophthalmology practice. Systems like IDx-DR (IDx Technologies Inc, USA) are FDA-approved for autonomous detection of referable diabetic retinopathy. For glaucoma, deep learning models assess optic nerve head morphology in fundus photographs to detect damage. In age-related macular degeneration, AI can quantify drusen and diagnose disease severity from both color fundus and optical coherence tomography images. AI has also been used in screening for retinopathy of prematurity, keratoconus, and dry eye disease. Beyond screening, AI can aid treatment decisions by forecasting disease progression and anti-VEGF response. However, potential limitations such as the quality and diversity of training data, lack of rigorous clinical validation, and challenges in regulatory approval and clinician trust must be addressed for the widespread adoption of AI. Two other significant hurdles include the integration of AI into existing clinical workflows and ensuring transparency in AI decision-making processes. With continued research to address these limitations, AI promises to enable earlier diagnosis, optimized resource allocation, personalized treatment, and improved patient outcomes. Besides, synergistic human-AI systems could set a new standard for evidence-based, precise ophthalmic care.},
}
@article {pmid39358867,
year = {2024},
author = {Hill, M and Andrews-Pfannkoch, C and Atherton, E and Knudsen, T and Trncic, E and Marmorstein, AD},
title = {Detection of Residual iPSCs Following Differentiation of iPSC-Derived Retinal Pigment Epithelial Cells.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {40},
number = {10},
pages = {680-687},
pmid = {39358867},
issn = {1557-7732},
support = {U01 EY030547/EY/NEI NIH HHS/United States ; },
mesh = {*Induced Pluripotent Stem Cells/cytology/metabolism ; *Retinal Pigment Epithelium/cytology/metabolism ; Humans ; *Cell Differentiation ; RNA-Binding Proteins/metabolism/genetics ; Real-Time Polymerase Chain Reaction ; Cells, Cultured ; Epithelial Cells/metabolism/cytology ; },
abstract = {Purpose: The goal of this study was to develop a lot release assay for iPSC residuals following directed differentiation of iPSCs to retinal pigment epithelial (RPE) cells. Methods: RNA Sequencing (RNA Seq) of iPSCs and RPE derived from them was used to identify pluripotency markers downregulated in RPE cells. Quantitative real time PCR (qPCR) was then applied to assess iPSC residuals in iPSC-derived RPE. The limit of detection (LOD) of the assay was determined by performing spike-in assays with known quantities of iPSCs serially diluted into an RPE suspension. Results: ZSCAN10 and LIN28A were among 8 pluripotency markers identified by RNA Seq as downregulated in RPE. Based on copy number and expression of pseudogenes and lncRNAs ZSCAN10 and LIN28A were chosen for use in qPCR assays for residual iPSCs. Reverse transcription PCR indicated generally uniform expression of ZSCAN10 and LIN28A in 21 clones derived from 8 iPSC donors with no expression of either in RPE cells derived from 5 donor lines. Based on qPCR, ZSCAN10, and LIN28A expression in iPSCs was generally uniform. The LOD for ZSCAN10 and LIN28A in qPCR assays was determined using spike in assays of RPE derived from 2 iPSC lines. Analysis of ΔΔCt found the limit of detection to be <0.01% of cells, equivalent to <1 iPSC/10,000 RPE cells in both iPSC lines. Conclusions: qPCR for ZSCAN10 and LIN28A detects <1 in 10,000 residual iPSCs in a population of iPSC-derived RPE providing an adequate LOD of iPSC residuals for lot release testing.},
}
@article {pmid39358477,
year = {2024},
author = {Monemian, M and Daneshmand, PG and Rakhshani, S and Rabbani, H},
title = {A new texture-based labeling framework for hyper-reflective foci identification in retinal optical coherence tomography images.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {22933},
pmid = {39358477},
issn = {2045-2322},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Retina/diagnostic imaging/pathology ; *Support Vector Machine ; Macular Degeneration/diagnostic imaging/pathology ; Diabetic Retinopathy/diagnostic imaging ; Macular Edema/diagnostic imaging ; Algorithms ; Image Processing, Computer-Assisted/methods ; Retinal Diseases/diagnostic imaging/pathology ; },
abstract = {An important abnormality in Optical Coherence Tomography (OCT) images is Hyper-Reflective Foci (HRF). This anomaly can be interpreted as a biomarker of serious retinal diseases such as Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) or the progression of disease from an early stage to a late one. In this paper, a new method is proposed for the identification of HRFs. The new method divides the OCT B-scan into patches and separately verifies each patch to determine whether or not the patch contains an HRF. The procedure of patch verification contains a texture-based framework which assigns appropriate labels according to intensity changes to each column and row. Then, a feature vector is extracted for each patch based on the assigned labels. The feature vectors are utilized in the training step of well-known classifiers like Support Vector Machine (SVM). Then, the classifiers are used to produce the labels for the test OCT images. The new method is evaluated on a public dataset including HRF labels. The experimental results show that the new method is capable of providing outstanding results in terms of speed and accuracy.},
}
@article {pmid39353792,
year = {2024},
author = {Yang, JM and Moon, SY and Lee, JY and Agalliu, D and Yon, DK and Lee, SW},
title = {Erratum to "COVID-19 Morbidity and Severity in Patients With Age-Related Macular Degeneration: A Korean Nationwide Cohort Study," American Journal of Ophthalmology, 239C, 159-169.},
journal = {American journal of ophthalmology},
volume = {268},
number = {},
pages = {421},
doi = {10.1016/j.ajo.2024.09.004},
pmid = {39353792},
issn = {1879-1891},
}
@article {pmid39353678,
year = {2024},
author = {Shah, P and Rafijah, N and Tang, Y and Sivaprasad, S and Mathis, T and Margaron, P and Kotecha, A},
title = {Baseline characteristics associated with the first year treatment interval of intravitreal faricimab in neovascular age-related macular degeneration (nAMD).},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {39353678},
issn = {2397-3269},
mesh = {Humans ; *Intravitreal Injections ; *Visual Acuity ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; Aged ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Double-Blind Method ; Aged, 80 and over ; Treatment Outcome ; Time Factors ; },
abstract = {AIMS: To identify baseline characteristics that best correlate to treatment interval for naive neovascular age-related macular degeneration patients treated with faricimab in the first year (Y1) of the TENAYA and LUCERNE phase 3 trials, and to further understand how these characteristics may impact treatment intervals.<br><br>METHODS: This post-hoc analysis of Y1 data from the TENAYA and LUCERNE trials evaluated ocular baseline characteristics associated with Y1 treatment intervals. Patients were categorised into three subgroups based on their Y1 treatment interval: Q16W, Q12W or Q8W. Baseline characteristics (central subfield thickness (CST), best-corrected visual acuity, presence of subretinal fluid in centre 1&#x2009;mm, presence of retinal fluid in centre 1 mm, macular neovascularisation (MNV) location and MNV type) were inputted into an R package 'rpart' to create a classification tree model. A data-driven tree model based on CST was fitted, producing CST subgroups of low, middle and high ranges. Within each CST subgroup, the model identified the most impactful variables and associated thresholds.<br><br>RESULTS: After fitting the data to produce data-driven CST ranges, the model chose MNV location, followed by MNV lesion type as the most impactful baseline characteristics with these factors having a p value <0.05 in a multivariate analysis.<br><br>CONCLUSIONS: Among the selected ocular baseline characteristics from TENAYA and LUCERNE trial, CST, MNV type and MNV location were seen as the most relevant variables to enable extension of treatment intervals during Y1. While this analysis provides insights for treatment intervals during the first year, further analysis incorporating Y2 data from the TENAYA and LUCERNE studies will be needed to assess factors influencing treatment intervals over a longer period.},
}
@article {pmid39355396,
year = {2024},
author = {Huang, ZH and Tu, XZ and Lin, Q and Tu, M and Lin, GC and Zhang, KP},
title = {Nomogram for predicting short-term response to anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration: An observational study.},
journal = {World journal of radiology},
volume = {16},
number = {9},
pages = {418-428},
pmid = {39355396},
issn = {1949-8470},
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is critical for managing neovascular age-related macular degeneration (nAMD), but understanding factors influencing treatment efficacy is essential for optimizing patient outcomes.<br><br>AIM: To identify the risk factors affecting anti-VEGF treatment efficacy in nAMD and develop a predictive model for short-term response.<br><br>METHODS: In this study, 65 eyes of exudative AMD patients after anti-VEGF treatment for &#x2265; 1 mo were observed using optical coherence tomography angiography. Patients were classified into non-responders (n = 22) and responders (n = 43). Logistic regression was used to determine independent risk factors for treatment response. A predictive model was created using the Akaike Information Criterion, and its performance was assessed with the area under the receiver operating characteristic curve, calibration curves, and decision curve analysis (DCA) with 500 bootstrap re-samples.<br><br>RESULTS: Multivariable logistic regression analysis identified the number of junction voxels [odds ratio = 0.997, 95% confidence interval (CI): 0.993-0.999, P = 0.010] as an independent predictor of positive anti-VEGF treatment outcomes. The predictive model incorporating the fractal dimension, number of junction voxels, and longest shortest path, achieved an area under the curve of 0.753 (95%CI: 0.622-0.873). Calibration curves confirmed a high agreement between predicted and actual outcomes, and DCA validated the model's clinical utility.<br><br>CONCLUSION: The predictive model effectively forecasts 1-mo therapeutic outcomes for nAMD patients undergoing anti-VEGF therapy, enhancing personalized treatment planning.},
}
@article {pmid39354837,
year = {2025},
author = {Artiaga, JCM and Wong, SW and Menon, D and Kumar, S and Dhoble, P and Thottarath, S and Nicholson, L},
title = {Reactivation of stable neovascular age-related macular degeneration following treat-and-extend regimen discontinuation.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {53},
number = {1},
pages = {76-83},
doi = {10.1111/ceo.14444},
pmid = {39354837},
issn = {1442-9071},
mesh = {Humans ; Female ; Male ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Visual Acuity ; Aged, 80 and over ; Retrospective Studies ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Fluorescein Angiography ; Middle Aged ; Follow-Up Studies ; Recurrence ; Withholding Treatment ; Incidence ; },
abstract = {BACKGROUND: To describe the incidence and pattern of reactivation of neovascular age-related macular degeneration (nAMD) following successful treatment with treat-and-extend intravitreal anti-vascular endothelial growth factor therapy.<br><br>METHODS: Consecutive patients with treated nAMD who did not require further treatment over a 6-month period and who attended their 3-monthly optical coherence tomography monitoring clinic in Moorfields Eye Hospital from 1 November 2019 to 31 January 2020 were included. Patients with diagnoses of macular neovascularization other than AMD, and patients with incomplete data were excluded. Baseline demographics recorded were age, sex, race, laterality, cause of macular neovascularization, drug, number of injections, and duration of treatment. Date, setting, symptoms, and time to retreatment were collected among patients with disease reactivation.<br><br>RESULTS: The medical records of 286 patients were included. Most patients were female (64.3%), white (68.18%), and were receiving aflibercept monotherapy (55.2%). Mean number of injections at baseline was 17.79&#x2009;&#xb1;&#x2009;11.74 (range 3-62) with a mean treatment duration of 39.47&#x2009;&#xb1;&#x2009;30.68&#x2009;months (range 2-139). Reactivation of AMD was identified in 32.2% of cases with 87% of recurrences identified via scheduled visit. The most common symptom was blurring of vision in 44.6%, while 39.1% were asymptomatic. Mean time from baseline to retreatment was 29.37&#x2009;&#xb1;&#x2009;22.40&#x2009;months (range 5-104), with 20.7%, 73.9% and 88.04% of these patients requiring retreatment within 1, 3, and 5&#x2009;years, respectively.<br><br>CONCLUSIONS: Despite prior treatment with no reactivation in 6&#x2009;months, 32.2% reactivate, 73.9% of which within 3&#x2009;years. A significant proportion, 39.1%, reactivated without symptoms necessitating regular monitoring in the first 5&#x2009;years.},
}
@article {pmid39354493,
year = {2024},
author = {Dabouz, R and Abram, P and Rivera, JC and Chemtob, S},
title = {Mast cells promote choroidal neovascularization in a model of age-related macular degeneration.},
journal = {Journal of neuroinflammation},
volume = {21},
number = {1},
pages = {247},
pmid = {39354493},
issn = {1742-2094},
support = {950-231837/CAPMC/CIHR/Canada ; },
mesh = {Animals ; *Mast Cells/metabolism/pathology ; *Choroidal Neovascularization/metabolism/pathology ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Macular Degeneration/pathology/metabolism ; Endothelial Cells/metabolism/pathology ; Choroid/pathology/metabolism ; Tryptases/metabolism ; Mice, Transgenic ; Ketotifen/pharmacology ; },
abstract = {'Wet' age-related macular degeneration (AMD) is characterized by pathologic choroidal neovascularization (CNV) that destroys central vision. Abundant evidence points to inflammation and immune cell dysfunction in the progression of CNV in AMD. Mast cells are resident immune cells that control the inflammatory response. Mast cells accumulate and degranulate in the choroid of patients with AMD, suggesting they play a role in CNV. Activated mast cells secrete various biologically active mediators, including inflammatory cytokines and proteolytic enzymes such as tryptase. We investigated the role of mast cells in AMD using a model of CNV. Conditioned media from activated mast cells exerts proangiogenic effects on choroidal endothelial cells and choroidal explants. Laser-induced CNV in vivo was markedly attenuated in mice genetically depleted of mast cells (Kit[W-sh/W-sh]) and in wild-type mice treated with mast cell stabilizer, ketotifen fumarate. Tryptase was found to elicit pronounced choroidal endothelial cell sprouting, migration and tubulogenesis; while tryptase inhibition diminished CNV. Transcriptomic analysis of laser-treated RPE/choroid complex revealed collagen catabolism and extracellular matrix (ECM) reorganization as significant events correlated in clusters of mast cell activation. Consistent with these analyses, compared to wildtype mice choroids of laser-treated mast cell-deficient mice displayed less ECM remodelling evaluated using collagen hybridizing peptide tissue binding. Findings herein provide strong support for mast cells as key players in the progression of pathologic choroidal angiogenesis and as potential therapeutic targets to prevent pathological neovascularization in 'wet' AMD.},
}
@article {pmid39350227,
year = {2024},
author = {Grimaldi, G and Cancian, G and Paris, A and Clerici, M and Volpe, G and Menghini, M},
title = {Intravitreal faricimab for treatment naïve patients with neovascular age-related macular degeneration: a real-world prospective study.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {70},
pmid = {39350227},
issn = {2056-9920},
abstract = {BACKGROUND: Intravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD.<br><br>METHODS: Single-centre, prospective cohort study of 21 eyes from 19 treatment-na&#xef;ve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up.<br><br>RESULTS: The study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n&#x2009;=&#x2009;14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p&#x2009;<&#x2009;0.01). The intended interval between injections was &#x2265;&#x2009;12 weeks in 42.86% of eyes. No cases of intraocular inflammation were observed, although 10% experienced retinal pigment epithelial tears.<br><br>CONCLUSIONS: Intravitreal faricimab demonstrated favourable efficacy, safety, and durability outcomes in a real-world cohort of treatment-na&#xef;ve nAMD patients.},
}
@article {pmid39349754,
year = {2025},
author = {Crincoli, E and Carnevali, A and Sacconi, R and Catania, F and Bandello, F and Querques, G},
title = {Differences in structural optical coherence tomography and infrared enface images between non-exudative macular neovascularizations secondary to AMD and pachychoroid disease.},
journal = {Eye (London, England)},
volume = {39},
number = {1},
pages = {88-93},
pmid = {39349754},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Aged ; Fluorescein Angiography/methods ; *Choroidal Neovascularization/etiology/diagnosis/diagnostic imaging ; *Macular Degeneration/complications/diagnosis ; Aged, 80 and over ; Middle Aged ; *Choroid Diseases/complications/diagnosis ; Infrared Rays ; Visual Acuity ; Follow-Up Studies ; Choroid ; },
abstract = {PURPOSE: To provide an analysis of structural optical coherence tomography (OCT) and enface infrared reflectance (IR) differences between non-exudative macular neovascularizations (NE MNVs) secondary to age-related macular degeneration (AMD) and NE MNVs secondary to pachychoroid spectrum.<br><br>METHODS: Patients diagnosed with NE-MNV documented by OCTA and dye angiography in the context of either AMD or pachychoroid spectrum were retrospectively included in AMD group and PACHY group respectively. Only treatment-na&#xef;ve NE MNVs showing persistence of non-exudative status for at least 1 year after diagnosis were considered. Availability of good quality structural OCT B scan and IR enface acquisitions both at baseline and at 1 year follow up was also required.<br><br>RESULTS: The study population included 15 eyes of 15 patients in AMD group and 13 eyes of 13 patients in PACHY group. AMD group showed at baseline a significantly wider pigment epithelium detachment (PED) apex angle (p&#x2009;=&#x2009;0.02), higher homogeneity of the PED (p&#x2009;=&#x2009;0.015), higher PED shadowing(p&#x2009;=&#x2009;0.03). Both groups experienced a widening of apex angle (flattening of the PED) during follow-up. Ten (76.9%) patients in PACHY group showed a hyporeflective halo at the margins of the PED at baseline compared to 3/15 (20.0%) patients in AMD group (0.007), with no significant changes at 1 year follow up (p&#x2009;=&#x2009;0.47).<br><br>CONCLUSION: NE-MNVs in pachychoroid eyes are characterized by sharper and more inhomogeneous PEDs with a lighter choroidal shadowing compared to NE-MNVs in AMD eyes. Moreover, they often show a hyporeflective halo around the lesion with IR imaging.},
}
@article {pmid39347541,
year = {2024},
author = {Viheriälä, T and Hongisto, H and Saari, L and Oksanen, M and Ilmarinen, T and Väärämäki, S and Uusitalo, H and Nevalainen, P and Skottman, H},
title = {Novel Human Induced Pluripotent Stem Cell-Based Model for Retinal Pigment Epithelial Cells to Reveal Possible Disease Mechanisms for Macular Degeneration in Pseudoxanthoma Elasticum.},
journal = {Journal of ophthalmology},
volume = {2024},
number = {},
pages = {6939920},
pmid = {39347541},
issn = {2090-004X},
abstract = {Pseudoxanthoma elasticum (PXE) is a rare metabolic disease with autosomal recessive inheritance. The manifestation in PXE is represented by retinal complications, pseudoxanthomas of the skin folding areas, and arterial calcification. The retinal complications are caused by the calcification of Bruch's membrane beneath retinal pigment epithelial cells (RPE) that can lead to retinal macular degeneration. The exact mechanism for the retinal pathophysiology is not known, and patients have variable symptoms and findings. Two induced pluripotent stem cell (hiPSC) lines from a patient carrying the common homozygous mutation c.3421C > T, p.Arg1141X in the ATP-binding cassette transporter gene (ABCC6; OMIM264800) were established and fully characterized. Then, RPE cells were differentiated, and molecular and functional characterization was conducted as a comparison to healthy controls. Data demonstrated that PXE-specific high-quality hiPSC lines can be established from a skin biopsy regardless of the skin-related disease phenotype and disease-specific RPE differentiation is feasible. The molecular and functional assessment of the PXE-specific RPE indicated increased pigmentation and reduced epithelial barrier functions as well as phagocytosis activity as compared to healthy controls. Although preliminary data, this indicates possible RPE-dependent factors that might explain the individual vulnerability of the retinas for macular degeneration in PXE. Future validation of the novel findings with additional PXE patients will be important.},
}
@article {pmid39347315,
year = {2024},
author = {Spanos, E and Roussos, A and Atzamoglou, S and Dimitriou, N and Markopoulos, I and Paroikakis, E and Karagiannis, D and Peponis, V and Karampelas, M},
title = {Adult-Onset Foveomacular Vitelliform Dystrophy With Unilateral Presentation: A Case Series.},
journal = {Cureus},
volume = {16},
number = {8},
pages = {e68214},
pmid = {39347315},
issn = {2168-8184},
abstract = {Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare condition affecting the macula that presents diagnostic and management challenges due to its varied manifestations and clinical overlap with other retinal disorders. As vitelliform lesions can occur in various conditions, such as Best disease and age-related macular degeneration, clinical presentation, multimodal imaging findings, and genetic testing can aid in accurate diagnosis. Although AOFVD typically affects both eyes, unilateral involvement can occur. This study presents four cases of unilateral AOFVD in female patients aged 43 to 66 years. Each patient was monitored for two years with fundoscopy and multimodal imaging, including color fundus photography, optical coherence tomography (OCT), OCT-angiography, fluorescein angiography, and fundus autofluorescence (FAF). All patients presented with a characterized solitary, subfoveal, yellow lesion on fundoscopy. FAF revealed intense hyperautofluorescence corresponding with the lesions. OCT revealed the accumulation of homogenous hyperreflective material between the retinal pigment epithelium and photoreceptors. No abnormal findings were observed in the fellow eyes. Subfoveal choroidal thickness was measured at 355 μm, 545 μm, 486 μm, and 669 μm in the affected eyes. While AOFVD typically manifests bilaterally, these cases demonstrate a unique unilateral presentation, highlighting the importance of comprehensive examination and differential diagnosis. Distinguishing cases with unilateral presentation from other conditions can be more challenging, so awareness of this unusual phenotype and its clinical characteristics must be raised. Choroidal thickness measurements provide additional insights into AOFVD pathophysiology, suggesting a potential association with the pachychoroid spectrum.},
}
@article {pmid39347185,
year = {2024},
author = {Choi, MY and Lee, WK},
title = {Treatment and Characteristics of Pachychoroid Neovasculopathy Accompanying Recalcitrant Intraretinal Cysts.},
journal = {Cureus},
volume = {16},
number = {8},
pages = {e68174},
pmid = {39347185},
issn = {2168-8184},
abstract = {PURPOSE: To evaluate the clinical characteristics associated with chronic pachychoroid neovasculopathy (PNV) accompanying recalcitrant intraretinal cysts.<br><br>METHODS: This is a retrospective, single-center, case-series study involving 20 eyes of 18 patients with PNV who did not respond to bevacizumab or ranibizumab and had to switch to aflibercept. Optical coherence tomography images were assessed before and after switching of intravitreal injection drug.<br><br>RESULTS: The intraretinal cysts involved the outer nuclear layer and inner nuclear layer in 15 patients (75.0%), and involved only the inner nuclear layer in five patients (25.0%). All participants showed retinal pigment epithelium atrophy and outer retinal layer defect including external limiting membrane defect co-localized to the intraretinal cystic lesion. With the initial injection, bevacizumab and ranibizumab injections did not show a significant decrease in choroidal thickness (CT). Twenty (100.0%) patients showed poor response of intraretinal cyst response (IRCR). After a switch to aflibercept, IRCR was good in 17 (85.0%) patients and poor in three (15.0%) patients. Reduction of CT was great in aflibercept injections (from 229.0 &#x3bc;m to 204.0 &#x3bc;m, median, p < 0.001). Best-corrected visual acuity did not show significant improvement before or after switching drugs.<br><br>CONCLUSION: Intravitreal aflibercept injections were more effective in the reduction of CT and IRCR than bevacizumab and ranibizumab injections. The primary source of the intraretinal cyst fluid could be from the choroid.},
}
@article {pmid39346973,
year = {2024},
author = {Wei, X and Hormel, TT and Renner, L and Neuringer, M and Jia, Y},
title = {Wide-field OCT angiography for non-human primate retinal imaging.},
journal = {Biomedical optics express},
volume = {15},
number = {8},
pages = {4642-4654},
pmid = {39346973},
issn = {2156-7085},
support = {P51 OD011092/OD/NIH HHS/United States ; R01 EY028141/EY/NEI NIH HHS/United States ; },
abstract = {Optical coherence tomography (OCT) is a well-established research tool for vision research in animal models capable of providing in vivo imaging of the retina. Structural OCT can be enhanced using OCT angiography (OCTA) processing in order to provide simultaneously acquired, automatically co-registered vascular information. Currently available OCT. Currently available OCTA lack either large field of view or high resolution. In this study we developed a wide-field (60-degree), high-resolution (10.5-µm optical transverse) and high-sensitivity (104-dB) OCTA-enabled system for non-human primate imaging and with it imaged multiple disease models, including models of age-related macular degeneration (AMD), Bardet-Biedl Syndrome (BBS), and the CLN7 variant of Batten disease. We demonstrate clear visualization of features including drusen, ellipsoid zone loss, vascular retinopathy, and retinal thinning in these eyes.},
}
@article {pmid39346368,
year = {2024},
author = {Parmar, M and Bhalodi, A and Attwal, HS and Kaur, A and Osseiran, R and Chavda, HS},
title = {Assessment of Relation between Periodontal Disease and Macular Degeneration.},
journal = {Journal of pharmacy &amp; bioallied sciences},
volume = {16},
number = {Suppl 3},
pages = {S2238-S2240},
pmid = {39346368},
issn = {0976-4879},
abstract = {BACKGROUND AND AIM: Periodontal disease may result in chronic inflammation and bacteremia in some people. The study aimed to evaluate the connection between periodontal disease and macular degeneration.<br><br>MATERIALS AND METHODS: The specialist dental surgeon conducted the dental examination using a community periodontal index probe. An ophthalmologist performed the eye examination. Age-related macular degeneration (AMD) was identified through specific criteria such as the existence of particular types of drusen and pigmentary abnormalities.<br><br>RESULTS: Two hundred participants were part of the study. According to the data, factors such as advanced age, limited education, low income, hypertension, cardiovascular disease (CVD), and hepatitis B surface antigen (HBsAg) presence were strongly linked to AMD in all participants.<br><br>CONCLUSION: Multiple studies have indicated a connection between periodontitis in the mouth and macular degeneration in individuals under 60 years of age.},
}
@article {pmid39345485,
year = {2024},
author = {Chew, LA and Grigsby, D and Hester, CG and Amason, J and McPherson, WK and Flynn, EJ and Visel, M and Flannery, JG and Rickman, CB},
title = {Truncated Complement Factor H Y402 Gene Therapy Cures C3 Glomerulonephritis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39345485},
issn = {2692-8205},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; },
abstract = {Patients with both age-related macular degeneration (AMD) and C3 glomerulonephritis (C3G) are challenged by the absence of effective therapies to reverse and eliminate their disease burden. Capitalizing on complement dysregulation as both a significant risk factor for AMD and the known pathophysiology of C3G, we investigated the potential for adeno-associated virus (AAV) delivery of complement factor H (CFH) to rescue C3G in a Cfh-/- mouse model of C3G. While past efforts to treat C3G using exogenous human CFH resulted in limited success before immune rejection led to a foreign protein response, our findings demonstrate the capacity for long-term AAV-mediated delivery of truncated CFH (tCFH) to restore inhibition of the alternative pathway of complement and ultimately reverse C3G without immune rejection. Comparing results from the administration of several tCFH vectors also revealed significant differences in their relative efficiency and efficacy. These discoveries pave the way for subsequent development of AAV-mediated tCFH replacement therapy for patients with C3G, while simultaneously demonstrating proof of concept for a parallel AAV-mediated tCFH gene augmentation therapy for patients with AMD.},
}
@article {pmid39343193,
year = {2024},
author = {Reiter, GS and Mai, J and Riedl, S and Birner, K and Frank, S and Bogunovic, H and Schmidt-Erfurth, U},
title = {AI in the clinical management of GA: A novel therapeutic universe requires novel tools.},
journal = {Progress in retinal and eye research},
volume = {103},
number = {},
pages = {101305},
doi = {10.1016/j.preteyeres.2024.101305},
pmid = {39343193},
issn = {1873-1635},
mesh = {Humans ; *Artificial Intelligence ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/physiopathology/diagnosis/therapy ; Fluorescein Angiography/methods ; Macular Degeneration/diagnosis/physiopathology/therapy/drug therapy ; Disease Management ; },
abstract = {Regulatory approval of the first two therapeutic substances for the management of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a major breakthrough following failure of numerous previous trials. However, in the absence of therapeutic standards, diagnostic tools are a key challenge as functional parameters in GA are hard to provide. The majority of anatomical biomarkers are subclinical, necessitating advanced and sensitive image analyses. In contrast to fundus autofluorescence (FAF), optical coherence tomography (OCT) provides high-resolution visualization of neurosensory layers, including photoreceptors, and other features that are beyond the scope of human expert assessment. Artificial intelligence (AI)-based methodology strongly enhances identification and quantification of clinically relevant GA-related sub-phenotypes. Introduction of OCT-based biomarker analysis provides novel insight into the pathomechanisms of disease progression and therapeutic, moving beyond the limitations of conventional descriptive assessment. Accordingly, the Food and Drug Administration (FDA) has provided a paradigm-shift in recognizing ellipsoid zone (EZ) attenuation as a primary outcome measure in GA clinical trials. In this review, the transition from previous to future GA classification and management is described. With the advent of AI tools, diagnostic and therapeutic concepts have changed substantially in monitoring and screening of GA disease. Novel technology combined with pathophysiological knowledge and understanding of the therapeutic response to GA treatments, is currently opening the path for an automated, efficient and individualized patient care with great potential to improve access to timely treatment and reduce health disparities.},
}
@article {pmid39342431,
year = {2025},
author = {Sin, TN and Tng, N and Dragoli, J and Ramesh Kumar, S and Villafuerte-Trisolini, C and Chung, SH and Tu, L and Le, SM and Shim, JH and Pepple, KL and Ravindran, R and Khan, IH and Moshiri, A and Thomasy, SM and Yiu, G},
title = {Safety and efficacy of CRISPR-mediated genome ablation of VEGFA as a treatment for choroidal neovascularization in nonhuman primate eyes.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {33},
number = {8},
pages = {3939-3954},
pmid = {39342431},
issn = {1525-0024},
support = {R01 EY030431/EY/NEI NIH HHS/United States ; R01 EY032238/EY/NEI NIH HHS/United States ; R01 EY033733/EY/NEI NIH HHS/United States ; U24 EY029904/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Choroidal Neovascularization/therapy/genetics/pathology/metabolism ; *Vascular Endothelial Growth Factor A/genetics ; *CRISPR-Cas Systems ; *Gene Editing/methods ; Dependovirus/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics ; Disease Models, Animal ; *Genetic Therapy/methods ; Genetic Vectors/genetics/administration &amp; dosage ; Macaca mulatta ; Humans ; Retina/metabolism/pathology ; Mice ; },
abstract = {CRISPR-based genome editing enables permanent suppression of angiogenic factors such as vascular endothelial growth factor (VEGF) as a potential treatment for choroidal neovascularization (CNV)-a major cause of blindness in age-related macular degeneration. We previously designed adeno-associated viral (AAV) vectors with S. pyogenes Cas 9 (SpCas9) and guide RNAs (gRNAs) to target conserved sequences in VEGFA across mouse, rhesus macaque, and human, with successful suppression of VEGF and laser-induced CNV in mice. Here, we advanced the platform to nonhuman primates and found that subretinal AAV8-SpCas9 with gRNAs targeting VEGFA may reduce VEGF and CNV severity as compared with SpCas9 without gRNAs. However, all eyes that received AAV8-SpCas9 regardless of gRNA presence developed subfoveal deposits, concentric macular rings, and outer retinal disruption that worsened at higher dose. Immunohistochemistry showed subfoveal accumulation of retinal pigment epithelial cells, collagen, and vimentin, disrupted photoreceptor structure, and retinal glial and microglial activation. Subretinal AAV8-SpCas9 triggered aqueous elevations in CCL2, but minimal systemic humoral or cellular responses against AAV8, SpCas9, or GFP reporter. Our findings suggest that CRISPR-mediated VEGFA ablation in nonhuman primate eyes may suppress VEGF and CNV, but can also lead to unexpected subretinal fibrosis, photoreceptor damage, and retinal inflammation despite minimal systemic immune responses.},
}
@article {pmid39341129,
year = {2024},
author = {Ren, C and Hu, C and Hu, M and Wu, Y and Yang, Y and Lu, F},
title = {Melatonin protects RPE cells from necroptosis and NLRP3 activation via promoting SERCA2-related intracellular Ca[2+] homeostasis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {135},
number = {},
pages = {156088},
doi = {10.1016/j.phymed.2024.156088},
pmid = {39341129},
issn = {1618-095X},
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Necroptosis/drug effects ; *Melatonin/pharmacology ; *Retinal Pigment Epithelium/drug effects/metabolism ; *Calcium/metabolism ; Mice ; *Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism ; *Iodates ; *Endoplasmic Reticulum Stress/drug effects ; Mice, Inbred C57BL ; Male ; Homeostasis/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Disease Models, Animal ; Mitochondria/drug effects/metabolism ; Inflammasomes/metabolism/drug effects ; Macular Degeneration/drug therapy ; Humans ; Retinal Degeneration/drug therapy/prevention &amp; control/metabolism ; },
abstract = {BACKGROUND: Melatonin is an antioxidant that also has anti-inflammatory effects. It has been reported to delay the progression of age-related macular degeneration (AMD), however, the mechanism has not been fully recognized.<br><br>PURPOSE: The aim of the present study was to investigate the effects of melatonin on sodium iodate (SI)-induced retinal degeneration and elucidate the specific mechanisms, then, provide novel targets in AMD treatment.<br><br>METHODS: Retinal degeneration mouse model and in vitro retinal pigment epithelium (RPE) death model were established by SI treatment. Melatonin was administrated intraperitoneally at a concentration of 20, 40 or 80 mg/kg for in vivo study or treated at 48 h before SI treatment. To confirm the therapeutic effects of melatonin on mouse, the retinal structure and visual function were evaluated. The specific cell death rates were determined by CCK-8 assay, PI staining and protein level of RIPK3. The cytosolic or mitochondrial calcium levels were determined by Fluo-4AM or Rhod-2AM staining. Mitochondrial functions including mitochondrial dynamics, mitochondrial membrane potential, or mitochondrial permeability pore opening were evaluated. The proteins involved in endoplasmic reticulum (ER) stress were measured by western blot assay while the genes expression in calcium signaling pathway were measured by RT-qPCR.<br><br>RESULTS: We show that melatonin protects RPE cells from necroptosis and NLRP3 inflammasome activation induced by SI. Mechanistically, melatonin suppresses ER stress and intracellular calcium overload triggered by SI through restoring the function of SERCA2. Silencing of SERCA2 or blocking of melatonin receptors inhibit the protective effects of melatonin. Melatonin reduces mitochondrial Ca[2+] levels and restores mitochondrial membrane potential. Constant mitochondrial Ca[2+] overload directly promote cell necroptosis through mitochondrial fission. Inhibition of mitochondrial fission by Mdivi-1 prevent necroptosis induced by SI without altering the level of mitochondrial Ca[2+].<br><br>CONCLUSIONS: The results confirmed that melatonin protects RPE cells from SI-induced injury by regulates MT2/SERCA2/Ca[2+] axis. This study highlighted the potential of melatonin in the treatment of AMD and elucidated the mechanism and signaling pathway that mediate the protective effects.},
}
@article {pmid39340634,
year = {2024},
author = {Cancian, G and Paris, A and Agliati, L and Rizzato, A and Clerici, M and Volpe, G and Menghini, M and Grimaldi, G},
title = {One-Year Real-World Outcomes of Intravitreal Faricimab for Previously Treated Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {11},
pages = {2985-2997},
pmid = {39340634},
issn = {2193-8245},
abstract = {INTRODUCTION: This study assessed the efficacy, durability, and safety of faricimab in patients with neovascular age-related macular degeneration (nAMD), previously treated with aflibercept or ranibizumab with unsatisfactory results.<br><br>METHODS: This was a single-center, prospective cohort study of all consecutive patients with nAMD switched to intravitreally administered faricimab from traditional anti-vascular endothelial growth factor (anti-VEGF) treatments between September 2022 and April 2023 because of unsatisfactory response (maximal fluid-free interval&#x2009;&#x2264;&#x2009;8&#xa0;weeks). Faricimab was administered with a loading dose of four 4-weekly injections, followed by a treat-and-extend regimen. The primary outcome measures were maximum fluid-free interval after the switch and last assigned treatment interval. Secondary outcome measures included best-corrected visual acuity (BCVA) and structural optical coherence tomography parameters.<br><br>RESULTS: Thirty-three eyes of 33 patients were included. Patients were followed for a median of 72&#xa0;weeks [interquartile range 61, 76]. Median maximum fluid-free treatment interval after switch to faricimab and the last assigned interval were significantly longer than before the switch (7 vs. 4&#xa0;weeks, p&#x2009;<&#x2009;0.001 and 8 vs. 5&#xa0;weeks, p&#x2009;<&#x2009;0.001, respectively). Significant improvements in central subfield thickness (353 vs. 281&#xa0;&#xb5;m), macular volume (2.46 vs. 2.16&#xa0;mm[3]), and pigment epithelial detachment height (198 vs. 150&#xa0;&#xb5;m) were observed (all p&#x2009;<&#x2009;0.001). BCVA remained stable at 0.4 versus 0.3&#xa0;logMAR before switch (p&#x2009;=&#x2009;0.190). One eye (3%) developed intraocular inflammation and one eye (3%) developed a retinal pigment epithelium tear.<br><br>CONCLUSIONS: Faricimab improved anatomical outcomes and allowed longer treatment intervals in patients with nAMD previously treated with other anti-VEGF therapies with unsatisfactory response, reducing treatment burden. A favorable safety profile was observed.},
}
@article {pmid39340236,
year = {2025},
author = {Cushley, LN and Leonard-Hawkhead, B and Jackson, AJ and Peto, T},
title = {Global certification of visual impairment registries: A scoping review.},
journal = {Acta ophthalmologica},
volume = {103},
number = {1},
pages = {7-15},
pmid = {39340236},
issn = {1755-3768},
support = {//Belfast Health and Social Care Trust Research Charitable Funds/ ; //Belfast Association for the Blind/ ; },
mesh = {Humans ; *Registries ; *Global Health ; Vision Disorders/epidemiology/diagnosis ; Visual Acuity ; Visually Impaired Persons/statistics &amp; numerical data ; Blindness/epidemiology/etiology ; Certification ; Vision, Low/epidemiology/etiology ; },
abstract = {BACKGROUND: Visual impairment is a global problem which is predicted to rise in the coming years. Some of the biggest causes of visual impairment globally include uncorrected refractive error, cataract and age-related macular degeneration. People with a visual impairment often require support and so many countries hold registers of visual impairment. These registers can sit at a national, regional or local level. This scoping review aims to identify which countries hold visual impairment registries and have published data from them.<br><br>METHODS: Medline All, Embase and EBSCOHost were searched using several search terms after consulting an information specialist. All papers after the year 2000 were included in the scoping review. All results are shown using a PRISMA diagram and presented narratively.<br><br>RESULTS: The total number of articles and papers identified was 1266; after screening and review, 57 articles were included in the review from 2000 to 2024. These articles came from 19 different countries and encompassed national, regional and local visual impairment databases. Many countries cited age-related macular degeneration as the major cause of blindness with diabetic retinopathy and glaucoma following. In less economically developed countries, refractive error was the main cause of sight loss. There were papers which focused on specific eye conditions such as glaucoma and diabetic retinopathy or on specific cohorts including working-age population and children. The leading causes of blindness in children appeared to be inherited retinal diseases, albinism and cerebral visual impairment.<br><br>CONCLUSION: Certification of visual impairment is held differently across the world. There is commonality among different countries regarding the major causes of visual impairment in both adults and children. The importance of holding visual impairment registers to support people with a visual impairment and to plan services is essential.},
}
@article {pmid39340175,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Wei, WB and Xu, J and Wang, YX},
title = {Prevalence and associations of dome-shaped maculas. The Beijing Eye Study.},
journal = {Acta ophthalmologica},
volume = {103},
number = {2},
pages = {177-185},
doi = {10.1111/aos.16764},
pmid = {39340175},
issn = {1755-3768},
support = {82271086//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Prevalence ; Male ; Female ; *Tomography, Optical Coherence/methods ; Middle Aged ; Beijing/epidemiology ; *Macula Lutea/pathology/abnormalities ; Aged ; Axial Length, Eye/pathology ; Visual Acuity ; Adult ; China/epidemiology ; },
abstract = {PURPOSE: To explore the prevalence and associated factors of a dome-shaped macula (DSM) in a general population.<br><br>METHODS: Out of the population-based Beijing Eye Study cohort (n&#x2009;=&#x2009;3468 participants), the investigation included all eyes with an axial length of &#x2265;25&#x2009;mm, and a randomized sample of eyes with an axial length of <25&#x2009;mm. Using optical coherence tomographic (OCT) images, we examined presence and height of DSMs, defined as an inward convexity of the foveal retinal pigment epithelium (RPE)/Bruch's membrane (BM) line, detectable in at least two OCT scans perpendicularly orientated to each other.<br><br>RESULTS: The study cohort consisted of 366 eyes (314 individuals) with a mean age of 63.7&#x2009;&#xb1;&#x2009;9.7&#x2009;years and a mean axial length of 24.8&#x2009;&#xb1;&#x2009;2.1&#x2009;mm (median: 25.1&#x2009;mm; range: 18.96-30.88&#x2009;mm). Prevalence of DSMs (found in 6/366 eyes; 1.9%; 95%CI: 1.0, 3.0) increased from 0/125 (0%) in non-myopic eyes to 1/152 (0.7%; 95%CI: 0.0, 2.0) in moderately myopic eyes, and to 6/83 (7.2%; 95%CI: 1.7, 12.7) in the highly myopic group. In multivariable analysis, higher DSM prevalence corelated with longer axial length (OR: 2.05; 95%CI: 1.36, 3.08; p&#x2009;<&#x2009;0.001) and higher stage of myopic macular degeneration (OR: 1.08; 95%CI: 1.01, 1.16; p&#x2009;=&#x2009;0.03). The mean maximal DSM height was 139&#x2009;&#xb1;&#x2009;107&#x2009;&#x3bc;m (median: 100&#x2009;&#x3bc;m; range: 25-350&#x2009;&#x3bc;m). It was associated with higher stage of myopic macular degeneration (beta: 0.24; p&#x2009;<&#x2009;0.001) and higher prevalence of macular BM defects (beta: 0.17; p&#x2009;<&#x2009;0.001). None of the DSMs showed a serous retinal detachment or relative choroidal thickening.<br><br>CONCLUSIONS: Higher DSM prevalence correlated non-linearly with longer axial length, with DSM height increasing with the presence of a BM defect. DSMs may be associated with an axial elongation-related BM overproduction in the fundus midperiphery in all meridians.},
}
@article {pmid39339769,
year = {2024},
author = {Sbai, O and Torrisi, F and Fabrizio, FP and Rabbeni, G and Perrone, L},
title = {Effect of the Mediterranean Diet (MeDi) on the Progression of Retinal Disease: A Narrative Review.},
journal = {Nutrients},
volume = {16},
number = {18},
pages = {},
pmid = {39339769},
issn = {2072-6643},
mesh = {Humans ; *Diet, Mediterranean ; *Disease Progression ; Macular Degeneration/prevention &amp; control/diet therapy ; Diabetic Retinopathy/prevention &amp; control/diet therapy ; Dietary Supplements ; Glaucoma/diet therapy ; Retinal Diseases/prevention &amp; control/diet therapy ; },
abstract = {Worldwide, the number of individuals suffering from visual impairment, as well as those affected by blindness, is about 600 million and it will further increase in the coming decades. These diseases also seriously affect the quality of life in working-age individuals. Beyond the characterization of metabolic, genetic, and environmental factors related to ocular pathologies, it is important to verify how lifestyle may participate in the induction of the molecular pathways underlying these diseases. On the other hand, scientific studies are also contributing to investigations as to whether lifestyle could intervene in modulating pathophysiological cellular responses, including the production of metabolites and neurohormonal factors, through the intake of natural compounds capable of interfering with molecular mechanisms that lead to ocular diseases. Nutraceuticals are promising in ameliorating pathophysiological complications of ocular disease such as inflammation and neurodegeneration. Moreover, it is important to characterize the nutritional patterns and/or natural compounds that may be beneficial against certain ocular diseases. The adherence to the Mediterranean diet (MeDi) is proposed as a promising intervention for the prevention and amelioration of several eye diseases. Several characteristic compounds and micronutrients of MeDi, including vitamins, carotenoids, flavonoids, and omega-3 fatty acids, are proposed as adjuvants against several ocular diseases. In this review, we focus on studies that analyze the effects of MeDi in ameliorating diabetic retinopathy, macular degeneration, and glaucoma. The analysis of knowledge in this field is requested in order to provide direction on recommendations for nutritional interventions aimed to prevent and ameliorate ocular diseases.},
}
@article {pmid39338355,
year = {2024},
author = {Seol, A and Kim, JE and Jin, YJ and Song, HJ and Roh, YJ and Kim, TR and Park, ES and Park, KH and Park, SH and Uddin, MS and Lee, SW and Choi, YW and Hwang, DY},
title = {Novel Therapeutic Effects of Euphorbia heterophylla L. Methanol Extracts in Macular Degeneration Caused by Blue Light in A2E-Laden ARPE-19 Cells and Retina of BALB/c Mice.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {9},
pages = {},
pmid = {39338355},
issn = {1424-8247},
support = {F23YY8109033//National Research Foundation of Korea/ ; PNU-Fellowship program//2023 BK FOUR Graduate School Innovation (Pusan National University)/ ; },
abstract = {Natural products with high antioxidant activity are considered as innovative prevention strategies to effectively prevent age-related macular degeneration (AMD) in the early stage because the generation of reactive oxygen species (ROS) leading to the development of drusen is reported as an important cause of this disease. To investigate the prevention effects of the methanol extracts of Euphorbia heterophylla L. (MEE) on AMD, its effects on the antioxidant activity, inflammatory response, apoptosis pathway, neovascularization, and retinal tissue degeneration were analyzed in N-retinylidene-N-retinylethanolamine (A2E)-landed spontaneously arising retinal pigment epithelia (ARPE)-19 cells and BALB/c mice after exposure to blue light (BL). The MEE contained 10 active components and showed high free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide (NO) radicals. The pretreatments of high-dose MEE remarkably suppressed the production of intracellular ROS (88.2%) and NO (25.2%) and enhanced (SOD) activity (84%) and the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in A2E + BL-treated ARPE-19 cells compared to Vehicle-treated group. The activation of the inducible nitric oxide synthase (iNOS)-induced cyclooxygenase-2 (COX-2) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was significantly inhibited in A2E + BL-treated ARPE-19 cells after the MEE pretreatment. The activation of the apoptosis pathway and increased expression of neovascular proteins (36% for matrix metalloproteinase (MMP)-9) were inhibited in the MEE pretreated groups compared to the Vehicle-treated group. Furthermore, the thickness of the whole retina (31%), outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) were significantly increased by the MEE pretreatment of BALB/c mice with BL-induced retinal degeneration. Therefore, these results suggest that the MEE, with its high antioxidative activity, protects against BL-induced retinal degeneration through the regulation of the antioxidative system, inflammatory response, apoptosis, and neovascularization in the AMD mouse model.},
}
@article {pmid39338244,
year = {2024},
author = {Dascalu, AM and Grigorescu, CC and Serban, D and Tudor, C and Alexandrescu, C and Stana, D and Jurja, S and Costea, AC and Alius, C and Tribus, LC and Dumitrescu, D and Bratu, D and Cristea, BM},
title = {Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review.},
journal = {Journal of personalized medicine},
volume = {14},
number = {9},
pages = {},
pmid = {39338244},
issn = {2075-4426},
abstract = {BACKGROUND/OBJECTIVES: Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. Intravitreal complement inhibitors are an emergent approach in the treatment of AMD, which have had encouraging results. This systematic review analyzes the outcomes and safety of complement inhibitor therapies for GA in AMD cases.<br><br>METHODS: A comprehensive search on the PubMed and Web of Science databases returned 18 studies involving various complement inhibitor agents, with a total of 4272 patients and a mean follow-up of 68.2 &#xb1; 20.4 weeks.<br><br>RESULTS: Most treated patients were white (96.8%) and female (55.8%), with a mean age of 78.3 &#xb1; 7.8 years and a mean GA area of 8.0 &#xb1; 3.9 mm[2]. There were no differences in visual function change between treated and control participants. The mean GA area change was 2.4 &#xb1; 0.7 mm[2] in treated participants vs. 2.7 &#xb1; 0.8 mm[2] in control groups (p < 0.001). The ocular and systemic side effects were similar to those of intravitreal anti-VEGF. A less-understood effect was that of the onset of choroidal neovascularization (CNV) in 1.1-13% of patients; this effect was found to be more frequent in patients with neovascular AMD in the fellow eye or nonexudative CNV in the study eye at baseline.<br><br>CONCLUSIONS: Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes.},
}
@article {pmid39337971,
year = {2024},
author = {Schwartz, L and Schwartz, J and Henry, M and Bakkar, A},
title = {Metabolic Shift and Hyperosmolarity Underlie Age-Related Macular Degeneration.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
pmid = {39337971},
issn = {2075-1729},
abstract = {Age-related macular degeneration (AMD) is both a poorly understood and devastating disease. Here, we analyze the physico-chemical forces at stake, including osmolarity, redox shift, and pressure due to inflammation. Hyperosmolarity plays a key role in diseases of the anterior segment of the eye such as glaucoma, cataracts or dry eyes, and corneal ulceration. However, its role in macular degeneration has been largely overlooked. Hyperosmolarity is responsible for metabolic shifts such as aerobic glycolysis which increases lactate secretion by Muller cells. Increased osmolarity will also cause neoangiogenesis and cell death. Because of its unique energetic demands, the macula is very sensitive to metabolic shifts. As a proof of concept, subretinal injection of drugs increasing hyperosmolarity such as polyethylene glycol causes neoangiogenesis and drusen-like structures in rodents. The link between AMD and hyperosmolarity is reinforced by the fact that treatments aiming to restore mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective. We suggest that metabolic shift, inflammation, and hyperosmolarity are hallmarks in the pathogenesis and treatment of AMD.},
}
@article {pmid39337623,
year = {2024},
author = {Lee, D and Tomita, Y and Miwa, Y and Kunimi, H and Nakai, A and Shoda, C and Negishi, K and Kurihara, T},
title = {Recent Insights into Roles of Hypoxia-Inducible Factors in Retinal Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {18},
pages = {},
pmid = {39337623},
issn = {1422-0067},
support = {18K09424//KAKENHI/ ; 24K12770//KAKENHI/ ; JP22gm1510007//AMED/ ; 23K15915//KAKENHI/ ; },
mesh = {Humans ; *Retinal Diseases/metabolism ; Animals ; Retina/metabolism/pathology ; Oxygen/metabolism ; Hypoxia-Inducible Factor 1/metabolism ; Diabetic Retinopathy/metabolism ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Hypoxia/metabolism ; },
abstract = {Hypoxia-inducible factors (HIFs) are transcriptional factors that function as strong regulators of oxygen homeostasis and cellular metabolisms. The maintenance of cellular oxygen levels is critical as either insufficient or excessive oxygen affects development and physiologic and pathologic conditions. In the eye, retinas have a high metabolic demand for oxygen. Retinal ischemia can cause visual impairment in various sight-threating disorders including age-related macular degeneration, diabetic retinopathy, and some types of glaucoma. Therefore, understanding the potential roles of HIFs in the retina is highly important for managing disease development and progression. This review focuses on the physiologic and pathologic roles of HIFs as regulators of oxygen homeostasis and cellular metabolism in the retina, drawing on recent evidence. Our summary will promote comprehensive approaches to targeting HIFs for therapeutic purposes in retinal diseases.},
}
@article {pmid39337609,
year = {2024},
author = {Yang, B and Yang, K and Chen, J and Wu, Y},
title = {Crocin Protects the 661W Murine Photoreceptor Cell Line against the Toxic Effects of All-Trans-Retinal.},
journal = {International journal of molecular sciences},
volume = {25},
number = {18},
pages = {},
pmid = {39337609},
issn = {1422-0067},
support = {82171064//National Natural Science Foundation of China/ ; 2022A1515012514//Guangdong Basic and Applied Basic Research Foundation/ ; JCYJ20230807091503007//Shenzhen Science and Technology Program/ ; },
mesh = {Animals ; Mice ; *Carotenoids/pharmacology ; *Oxidative Stress/drug effects ; *Retinaldehyde/metabolism ; Cell Line ; NF-E2-Related Factor 2/metabolism ; Apoptosis/drug effects ; Signal Transduction/drug effects ; Antioxidants/pharmacology ; Heme Oxygenase-1/metabolism ; Kelch-Like ECH-Associated Protein 1/metabolism ; Ferroptosis/drug effects ; DNA Damage/drug effects ; Photoreceptor Cells, Vertebrate/drug effects/metabolism ; Photoreceptor Cells/drug effects/metabolism ; Macular Degeneration/metabolism/drug therapy/pathology ; Protective Agents/pharmacology ; Lipid Peroxidation/drug effects ; Pyroptosis/drug effects ; },
abstract = {Age-related macular degeneration (AMD) is a common disease contributing to vision loss in the elderly. All-trans-retinal (atRAL) is a retinoid in the retina, and its abnormal accumulation exhibits toxicity to the retina and promotes oxidative stress-induced photoreceptor degeneration, which plays a crucial role in AMD progression. Crocin is a natural product extracted from saffron, which displays significant antioxidant and anti-inflammatory effects. The present study elucidates the protective effects of crocin on photoreceptor cell damage by atRAL and its potential mechanisms. The results revealed that crocin significantly attenuated cytotoxicity by repressing oxidative stress, mitochondrial injury, and DNA damage in atRAL-loaded photoreceptor cells. Moreover, crocin visibly inhibited DNA damage-induced apoptosis and gasdermin E (GSDME)-mediated pyroptosis in photoreceptor cells after exposure to atRAL. It was also observed that crocin distinctly prevented an increase in Fe[2+] levels and lipid peroxidation caused by atRAL via suppressing the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor-erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway, thereby ameliorating photoreceptor cell ferroptosis. In short, these findings provide new insights that crocin mitigates atRAL-induced toxicity to photoreceptor cells by inhibiting oxidative stress, apoptosis, pyroptosis, and ferroptosis.},
}
@article {pmid39337590,
year = {2024},
author = {Hailey, DR and Kanjilal, D and Koulen, P},
title = {Differential Expression of Mitogen-Activated Protein Kinase Signaling Pathways in the Human Choroid-Retinal Pigment Epithelial Complex Indicates Regional Predisposition to Disease.},
journal = {International journal of molecular sciences},
volume = {25},
number = {18},
pages = {},
pmid = {39337590},
issn = {1422-0067},
support = {R01 EY030747/EY/NEI NIH HHS/United States ; 1R01EY030747-01/NH/NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; *Choroid/metabolism/pathology ; *MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/metabolism/genetics ; Disease Susceptibility ; Macular Degeneration/metabolism/pathology/genetics ; },
abstract = {The retina is composed of neuronal layers that include several types of interneurons and photoreceptor cells, and separate underlying retinal pigment epithelium (RPE), Bruch's membrane, and choroid. Different regions of the human retina include the fovea, macula, and periphery, which have unique physiological functions and anatomical features. These regions are also unique in their protein expression, and corresponding cellular and molecular responses to physiological and pathophysiological stimuli. Skeie and Mahajan analyzed regional protein expression in the human choroid-RPE complex. Mitogen-Activated Protein Kinase (MAPK) signaling pathways have been implicated in responses to stimuli such as oxidative stress and inflammation, which are critical factors in retina diseases including age-related macular degeneration. We, therefore, analyzed the Skeie and Mahajan, 2014, dataset for regional differences in the expression of MAPK-related proteins and discussed the potential implications in retinal diseases presenting with regional signs and symptoms. Regional protein expression data from the Skeie and Mahajan, 2014, study were analyzed for members of signaling networks involving MAPK and MAPK-related proteins, categorized by specific MAPK cascades, such as p38, ERK1/2, and JNK1/2, both upstream or downstream of the respective MAPK and MAPK-related proteins. We were able to identify 207 MAPK and MAPK-related proteins, 187 of which belonging to specific MAPK cascades. A total of 31 of these had been identified in the retina with two proteins, DLG2 and FLG downstream, and the other 29 upstream, of MAPK proteins. Our findings provide evidence for potential molecular substrates of retina region-specific disease manifestation and potential new targets for therapeutics development.},
}
@article {pmid39337098,
year = {2024},
author = {Tîrziu, AT and Susan, M and Susan, R and Sonia, T and Harich, OO and Tudora, A and Varga, NI and Tiberiu-Liviu, D and Avram, CR and Boru, C and Munteanu, M and Horhat, FG},
title = {From Gut to Eye: Exploring the Role of Microbiome Imbalance in Ocular Diseases.},
journal = {Journal of clinical medicine},
volume = {13},
number = {18},
pages = {},
pmid = {39337098},
issn = {2077-0383},
abstract = {Background: The gut microbiome plays a crucial role in human health, and recent research has highlighted its potential impact on ocular health through the gut-eye axis. Dysbiosis, or an imbalance in the gut microbiota, has been implicated in various ocular diseases. Methods: A comprehensive literature search was conducted using relevant keywords in major electronic databases, prioritizing recent peer-reviewed articles published in English. Results: The gut microbiota influences ocular health through immune modulation, maintenance of the blood-retinal barrier, and production of beneficial metabolites. Dysbiosis can disrupt these mechanisms, contributing to ocular inflammation, tissue damage, and disease progression in conditions such as uveitis, age-related macular degeneration, diabetic retinopathy, dry eye disease, and glaucoma. Therapeutic modulation of the gut microbiome through probiotics, prebiotics, synbiotics, and fecal microbiota transplantation shows promise in preclinical and preliminary human studies. Conclusions: The gut-eye axis represents a dynamic and complex interplay between the gut microbiome and ocular health. Targeting the gut microbiome through innovative therapeutic strategies holds potential for improving the prevention and management of various ocular diseases.},
}
@article {pmid39337030,
year = {2024},
author = {Macha, N and Yu, M and Sapieha, P and Klier, S and Ghosh, A and White, L and Maturi, RK},
title = {Multifocal Electroretinography Changes after UBX1325 (Foselutoclax) Treatment in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {18},
pages = {},
pmid = {39337030},
issn = {2077-0383},
support = {N/A//a clinical trial agreement between UNITY Biotherapeutics and Retina Partners Midwest/ ; },
abstract = {Background/Objectives: The objective of this study was to determine the treatment effect of foselutoclax in neovascular age-related macular degeneration (AMD) by multifocal electroretinography (mfERG) and evaluate mfERG as a potential clinical endpoint in AMD studies. Methods: A total of five subjects were included in the study who had active choroidal neovascularization and a history of at least two anti-vascular endothelial growth factor (VEGF) injections in the last 6 months. Subjects received a 50 µL intravitreal injection of foselutoclax at the baseline visit and Weeks 4, 24, and 28 of the study period. Results: After foselutoclax treatment, the largest improvement in the mfERG N1-P1 response density occurred at Week 8 as three of five subjects achieved a ≥20% gain. In addition, three of five subjects demonstrated a BCVA improvement of ≥5 ETDRS letters over baseline at Weeks 4, 8, and 24. The mean change in BCVA demonstrated statistical significance in Weeks 4 and 8, showing increases of 5 (p = 0.02) and 6.2 (p = 0.02) letters, respectively. Conclusions: Foselutoclax treatment was shown to have the potential to recover outer retinal function as determined by mfERG and BCVA at approximately Week 8 of treatment.},
}
@article {pmid39335605,
year = {2024},
author = {Sendecki, A and Ledwoń, D and Tuszy, A and Nycz, J and Wąsowska, A and Boguszewska-Chachulska, A and Mitas, AW and Wylęgała, E and Teper, S},
title = {Fundus Image Deep Learning Study to Explore the Association of Retinal Morphology with Age-Related Macular Degeneration Polygenic Risk Score.},
journal = {Biomedicines},
volume = {12},
number = {9},
pages = {},
pmid = {39335605},
issn = {2227-9059},
support = {07/010/BK_24/1034 (BK- 378 289/RIB1/2024)//Silesian University of Technology/ ; STRATEGMED1/234261/2/NCBR/2014//National Centre for Research and Development/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a complex eye disorder with an environmental and genetic origin, affecting millions worldwide. The study aims to explore the association between retinal morphology and the polygenic risk score (PRS) for AMD using fundus images and deep learning techniques.<br><br>METHODS: The study used and pre-processed 23,654 fundus images from 332 subjects (235 patients with AMD and 97 controls), ultimately selecting 558 high-quality images for analysis. The fine-tuned DenseNet121 deep learning model was employed to estimate PRS from single fundus images. After training, deep features were extracted, fused, and used in machine learning regression models to estimate PRS for each subject. The Grad-CAM technique was applied to examine the relationship between areas of increased model activity and the retina's morphological features specific to AMD.<br><br>RESULTS: Using the hybrid approach improved the results obtained by DenseNet121 in 5-fold cross-validation. The final evaluation metrics for all predictions from the best model from each fold are MAE = 0.74, MSE = 0.85, RMSE = 0.92, R[2] = 0.18, MAPE = 2.41. Grad-CAM heatmap evaluation showed that the model decisions rely on lesion area, focusing mostly on the presence of drusen. The proposed approach was also shown to be sensitive to artifacts present in the image.<br><br>CONCLUSIONS: The findings indicate an association between fundus images and AMD PRS, suggesting that deep learning models may effectively estimate genetic risk for AMD from retinal images, potentially aiding in early detection and personalized treatment strategies.},
}
@article {pmid39334773,
year = {2024},
author = {Ye, J and Cheng, J and Xiong, R and Chen, H and Huang, S and Li, H and Pang, J and Zhang, X and Zhu, H},
title = {Effects and Mechanisms of Lutein on Aging and Age-Related Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {9},
pages = {},
pmid = {39334773},
issn = {2076-3921},
abstract = {Aging and age-related diseases are serious public health issues that are receiving growing attention from researchers. Lutein has a critical function in the prevention and management of these issues. Possible mechanisms mainly include suppressing inflammation and oxidative stress, regulating cell activity, and modulating the levels of toxic substances. In this narrative review paper, we sum up the most current developments in the study of the effects of lutein on aging and five age-related diseases (age-related macular degeneration, cataracts, Alzheimer's disease, Parkinson's disease, and osteoporosis), and fundamental mechanisms are reviewed. The bioavailability of lutein and the strategies to improve its bioavailability are discussed. This piece of work can bring a clearer comprehension of the protective effects of lutein against aging and age-related diseases and can be also helpful for developing lutein as functional food and dietary supplements for these age-related diseases.},
}
@article {pmid39333742,
year = {2024},
author = {Miyatani, T and Tanaka, H and Numa, K and Uehara, A and Otsuki, Y and Hamuro, J and Kinoshita, S and Sotozono, C},
title = {Clustered ARPE-19 cells distinct in mitochondrial membrane potential may play a pivotal role in cell differentiation.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {22391},
pmid = {39333742},
issn = {2045-2322},
support = {JP20K18405//Japan Society for the Promotion of Science/ ; },
mesh = {*Cell Differentiation ; Humans ; *Membrane Potential, Mitochondrial ; *Retinal Pigment Epithelium/metabolism/cytology ; Cell Line ; Mitochondria/metabolism ; Rotenone/pharmacology ; Macular Degeneration/metabolism/pathology ; Animals ; Mice ; Cell Aggregation/drug effects ; },
abstract = {Age-related macular degeneration (AMD) is associated with the dysfunction and degeneration of retinal pigment epithelium (RPE) cells. Here, we examined how the formation and expansions of cell clusters are regulated by the differentiation of the RPE cells. In this study, ARPE-19 cells were cultivated in standard or differentiation media, i.e., without or with nicotinamide, to evaluate the spreading of cell clusters specified with differentiated cell phenotypes. Mitochondria membrane potential (MMP) and the distribution of the RPE cell clusters was also monitored with or without rotenone, a mitochondrial electron transport chain (ETC) complex I inhibitor. Cultured ARPE-19 cells generated scattered cell clusters composed mostly of smaller size cells expressing the differentiation markers mouse anti-cellular retinaldehyde-binding protein (CRALBP) and Bestrophin only in differentiation medium. After the increase of the number of clusters, the clusters appeared to paracellularly merge, resulting in expansion of the area occupied by the clusters. Of note, the cells within the clusters selectively had high MMP and were in accordance with the expression of RPE differentiation markers. Rotenone repressed the formation of the clusters and decreased intracellular MMP. The above results suggest that clustering of RPE cells with functional mitochondria plays a pivotal role in RPE cell differentiation process and the ETC complex I inhibition greatly influences the composition of RPE cells that are degenerated or differentiation disposed.},
}
@article {pmid39333160,
year = {2024},
author = {Kim, JH and Park, SM and Kim, JW and Kim, CG},
title = {Clinical characteristics and long-term treatment outcomes of polypoidal choroidal vasculopathy with classic type leakage.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {22346},
pmid = {39333160},
issn = {2045-2322},
mesh = {Humans ; Female ; Male ; Aged ; Retrospective Studies ; Treatment Outcome ; Middle Aged ; *Visual Acuity ; *Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Angiogenesis Inhibitors/therapeutic use ; Choroidal Neovascularization/drug therapy ; Choroid/blood supply/pathology/diagnostic imaging ; Choroid Diseases/drug therapy/diagnosis ; Tomography, Optical Coherence ; Intravitreal Injections ; Ranibizumab/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Polypoidal Choroidal Vasculopathy ; },
abstract = {To investigate long-term treatment outcomes of polypoidal choroidal vasculopathy (PCV) with classic type leakage and to compare the outcomes with those of PCV without classic type leakage. This retrospective study included 153 patients diagnosed with PCV and treated with anti-vascular endothelial growth factor (VEGF). Patients showing classic type leakage on fluorescein angiography were included in the classic type leakage group (N = 40, 26.1%), and those without classic type leakage were included in the occult group (N = 113, 73.9%). The best-corrected visual acuity (BCVA) at baseline and 24 months, changes in BCVA, incidence of fibrosis, and lesion reactivation after initial loading injections were compared between the two groups. There was no significant difference in the baseline BCVA between the classic type leakage group (mean logarithm of minimal angle of resolution 0.67 ± 0.53[Snellen equivalents = 20/93]) and the occult group (0.55 ± 0.49[20/70])(P = 0.639). In addition, the BCVA at 24 months (0.44 ± 0.53[20/55] vs. 0.38 ± 0.41[20/47])(P = 1.000), changes in BCVA (0.22 ± 0.42 improvement[2.2 lines] vs. 0.16 ± 0.36 improvement[1.6 lines]) (P = 0.366), and lesion reactivation (P = 0.787) did not differ between the two groups. The incidence of fibrosis was higher in the classic type leakage group (37.5%) than in the occult group (14.2%) (P = 0.002). Although the incidence of fibrosis was higher in PCVs with classic type leakage, the overall treatments were not significantly different between PCVs with and without classic type leakage. In addition, substantial visual improvement was noted at 24 months, suggesting that PCVs with classic type leakage can be effectively treated with anti-VEGF therapy.},
}
@article {pmid39332313,
year = {2024},
author = {Li, CH and Yang, TM and Fitriana, I and Fang, TC and Wu, LH and Hsiao, G and Cheng, YW},
title = {Maintaining KEAP1 levels in retinal pigment epithelial cells preserves their viability during prolonged exposure to artificial blue light.},
journal = {Journal of photochemistry and photobiology. B, Biology},
volume = {260},
number = {},
pages = {113037},
doi = {10.1016/j.jphotobiol.2024.113037},
pmid = {39332313},
issn = {1873-2682},
mesh = {*Kelch-Like ECH-Associated Protein 1/metabolism ; *Light ; *Retinal Pigment Epithelium/metabolism/cytology/radiation effects ; *Cell Survival/radiation effects/drug effects ; Animals ; *NF-E2-Related Factor 2/metabolism ; Humans ; Mice ; *Autophagy/radiation effects/drug effects ; Sequestosome-1 Protein/metabolism ; Cell Line ; Heme Oxygenase-1/metabolism ; Oxidative Stress/radiation effects ; Epithelial Cells/metabolism/radiation effects/cytology ; Blue Light ; },
abstract = {Exposure to artificial blue light, one of the most energetic forms of visible light, can increase oxidative stress in retinal cells, potentially enhancing the risk of macular degeneration. Retinal pigment epithelial (RPE) cells play a crucial role in this process; the loss of RPE cells is the primary pathway through which retinal degeneration occurs. In RPE cells, Kelch-like ECH-associated protein 1 (KEAP1) is located in both the nucleus and cytosol, where it binds to nuclear factor erythroid 2-related factor 2 (NRF2) and p62 (sequestosome-1), respectively. Blue light exposure activates the NRF2-heme oxygenase 1 (HMOX1) axis through both canonical and noncanonical p62 pathways thereby reducing oxidative damage, and initiates autophagy, which helps remove damaged proteins. These protective responses may support the survival of RPE cells. However, extended exposure to blue light drastically decreases the viability of RPE cells. This exposure diminishes the ability of KEAP1 to bind to p62 and reduces the level of KEAP1. Inhibition of autophagy does not prevent KEAP1 degradation, the NRF2-HMOX1 axis, or blue-light-induced cytotoxicity. However, proteasome inhibitor along with a transient increase in the amount of KEAP1 in RPE cells, partially restores the p62-KEAP1 complex and reduces blue-light-induced cytotoxicity. In vivo studies confirmed the downregulation of KEAP1 in damaged RPE cells. Mice subjected to periodic blue light exposure exhibited significant atrophy in the outer retina, particularly in the peripheral areas. Additionally, there was a significant decrease in c-wave electroretinography and pupillary light reflex, indicating functional impairments in both visual and nonvisual physiological processes. These data underscore the essential role of KEAP1 in managing oxidative defense and autophagy pathways triggered by blue light exposure in RPE cells.},
}
@article {pmid39329682,
year = {2024},
author = {Kulyabin, M and Zhdanov, A and Pershin, A and Sokolov, G and Nikiforova, A and Ronkin, M and Borisov, V and Maier, A},
title = {Segment Anything in Optical Coherence Tomography: SAM 2 for Volumetric Segmentation of Retinal Biomarkers.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {9},
pages = {},
pmid = {39329682},
issn = {2306-5354},
abstract = {Optical coherence tomography (OCT) is a non-invasive imaging technique widely used in ophthalmology for visualizing retinal layers, aiding in the early detection and monitoring of retinal diseases. OCT is useful for detecting diseases such as age-related macular degeneration (AMD) and diabetic macular edema (DME), which affect millions of people globally. Over the past decade, the area of application of artificial intelligence (AI), particularly deep learning (DL), has significantly increased. The number of medical applications is also rising, with solutions from other domains being increasingly applied to OCT. The segmentation of biomarkers is an essential problem that can enhance the quality of retinal disease diagnostics. For 3D OCT scans, AI is beneficial since manual segmentation is very labor-intensive. In this paper, we employ the new SAM 2 and MedSAM 2 for the segmentation of OCT volumes for two open-source datasets, comparing their performance with the traditional U-Net. The model achieved an overall Dice score of 0.913 and 0.902 for macular holes (MH) and intraretinal cysts (IRC) on OIMHS and 0.888 and 0.909 for intraretinal fluid (IRF) and pigment epithelial detachment (PED) on the AROI dataset, respectively.},
}
@article {pmid39329222,
year = {2025},
author = {Denniss, J and Baggaley, HC and Astle, AT},
title = {Frequency-of-seeing curves (psychometric functions) for perimetric stimuli in age-related macular degeneration.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {45},
number = {1},
pages = {301-307},
pmid = {39329222},
issn = {1475-1313},
support = {Postdoctoral Award (to ATA)//National Institute for Health and Care Research/ ; Postdoctoral Award (to JD &amp; ATA)//College of Optometrists/ ; },
mesh = {Humans ; Female ; Aged ; Male ; *Visual Field Tests/methods ; *Macular Degeneration/physiopathology ; Aged, 80 and over ; *Visual Fields/physiology ; Visual Acuity/physiology ; Psychometrics ; },
abstract = {PURPOSE: Frequency-of-seeing (FoS) curves (psychometric functions) for perimetric stimuli have been widely used in computer simulations of new visual field test procedures. FoS curves for age-related macular degeneration (AMD) are not available in the literature and are needed for the development of improved microperimetry test procedures, which are of particular interest for use as clinical trial endpoints.<br><br>METHODS: Data were refitted from a previous study to generate FoS curves for 20 participants with AMD, each tested at nine locations within the central 10&#xb0;. Stimulus parameters, background luminance and dB scale were matched to the MAIA-2 microperimeter, and stimuli were presented in a method of constant stimuli to build up FoS curves over multiple runs. FoS curves were fitted with a modified cumulative Gaussian function. The relationship between sensitivity and slope of fitted FoS curves was modelled by robust linear regression, producing models both with and without an eccentricity parameter.<br><br>RESULTS: FoS curves were satisfactorily fitted to data from 174 visual field locations in 20 participants (age 65-83&#x2009;years, 11 female). Each curve was made up of a median of 243 (range 177-297) stimulus presentations over a median of 12 (range 9-32) levels. Median sensitivity was 25.5&#x2009;dB (range 3.8-31.4&#x2009;dB). The median slope (SD of fitted function) was 1.6&#x2009;dB (range 0.5-8.5&#x2009;dB). As in previous studies of other conditions, the slope of fitted FoS curves increased as sensitivity decreased (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: FoS are provided for participants with AMD, as well as models of the relationship between sensitivity and slope. These fitted models and data may be useful for computer simulation studies of microperimetry procedures. Full details of the fitted curves are provided as supporting information.},
}
@article {pmid39329215,
year = {2025},
author = {Deng, J and Qin, Y},
title = {Investigating the Link between Psychological Well-Being and Early-Stage Age-Related Macular Degeneration: A Mendelian Randomization Analysis.},
journal = {Current eye research},
volume = {50},
number = {2},
pages = {190-202},
doi = {10.1080/02713683.2024.2408757},
pmid = {39329215},
issn = {1460-2202},
mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Macular Degeneration/psychology/genetics ; Neuroticism ; Male ; Female ; Genetic Predisposition to Disease ; Risk Factors ; Aged ; Polymorphism, Single Nucleotide ; *Stress, Psychological ; Psychological Well-Being ; },
abstract = {PURPOSE: While some studies have started to focus on the link between psychological well-being and age-related macular degeneration (AMD), the relationship remains uncertain. Our research aims to provide new insights into this association, laying a foundation for future interventions and addressing existing knowledge gaps.<br><br>METHODS: We utilized the "TwoSampleMR" package in R for a bidirectional Mendelian randomization analysis of psychological well-being (subjective well-being, depression, neuroticism, and Sensitivity to Environmental Stress and Adversity) and early-stage AMD. Causal effects were estimated using the inverse-variance weighted method, and additional methods included weighted median and MR-Egger regression. Sensitivity analyses included Cochran's Q test, MR-Egger intercept analysis, MR-PRESSO, and leave-one-out analysis.<br><br>RESULTS: The study found that the population with genetic predisposition to neuroticism had a 39.7% lower risk of early-stage AMD (OR = 0.603, 95% CI = 0.385-0.945, p&#x2009;=&#x2009;0.027). Conversely, the population with genetic predisposition to subjective well-being had a 3.2% increased risk of early-stage AMD (OR = 1.032, 95% CI = 1.003-1.063, p&#x2009;=&#x2009;0.029). No significant causal relationships were found from depression or Sensitivity to Environmental Stress and Adversity to early-stage AMD, nor from early-stage AMD to psychological well-being.<br><br>CONCLUSION: This study provides preliminary evidence that the relationship between psychological well-being and early-stage AMD may be complex and multifaceted. It suggests that moderate neuroticism levels might reduce early-stage AMD risk through health behaviors, pathophysiological mechanisms, and other factors, while high subjective well-being levels might increase this risk similarly. However, these findings are insufficient for preventive strategies due to a lack of substantial evidence and still require extensive experimental research for further validation.},
}
@article {pmid39329213,
year = {2025},
author = {Li, Y and Zhang, R and Li, J and Wang, L and Zhou, G},
title = {Dysfunction of Endothelial Cell-Mediated Intercellular Communication and Metabolic Pathways in Age-Related Macular Degeneration.},
journal = {Current eye research},
volume = {50},
number = {2},
pages = {169-181},
doi = {10.1080/02713683.2024.2407361},
pmid = {39329213},
issn = {1460-2202},
mesh = {Humans ; *Cell Communication/physiology ; Retinal Pigment Epithelium/metabolism/pathology ; *Metabolic Networks and Pathways ; *Endothelial Cells/metabolism/pathology ; *Macular Degeneration/metabolism/genetics ; Signal Transduction ; *Wet Macular Degeneration/metabolism/genetics ; Gene Expression Profiling ; Aged ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, but the therapies are not satisfactory. This study aimed to find AMD specific features through the analysis of high-throughput sequencing.<br><br>METHODS: In this study, we integrated six projects containing single-cell RNA sequencing (scRNA-seq) data to perform a comprehensive analysis for AMD samples in the tissues of retina and retinal pigment epithelium/choroid, and in the positions of macula and periphery. Differentially expressed genes (DEGs) were analyzed and crucial signaling pathways were identified across cell types and between the macula and periphery. The intercellular signaling transduction among cell types were inferred by "CellChat" to build cell-cell communication network under normal and AMD conditions, and verified at the transcriptional level. The CD31+ endothelial cells were obtained to evaluate the enrichment of KEGG pathways in atrophic and neovascular AMD, and GSVA was adopted to discover differential metabolic signals in each AMD type.<br><br>RESULTS: Thirteen major cell types were identified in the integrated scRNA-seq data. Although no disease-specific cell type or differential cell proportion was found, DEGs and enriched pathways were shown in cell-type- and position-dependent manners. Severe impairment of endothelial cell-mediated cell interactions was found in the signaling transduction network of the macula, and compromised cell interactions were observed in the periphery. Furthermore, distinct signaling pathways and metabolic states were uncovered in atrophic and neovascular AMD. Striking reduction in energy metabolism, lipid metabolism, and oxidative stress was indicated in the atrophic AMD.<br><br>CONCLUSION: Conclusively, we discover aberrant signals and metabolic pathways in AMD samples, providing insight into mechanisms and potential therapeutic targets for the AMD treatment.},
}
@article {pmid39328827,
year = {2025},
author = {Barakat, MR and Brown, D and Hu, A and Khurana, RN and Marcus, D and Pearlman, J and Wykoff, CC and Kapik, B and Ciulla, T},
title = {Safety and Tolerability of Suprachoroidal Axitinib Injectable Suspension, for Neovascular Age-related Macular Degeneration; Phase I/IIa Open-Label, Dose-Escalation Trial.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100586},
pmid = {39328827},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the safety and tolerability of a single dose of axitinib injectable suspension (CLS-AX), a pan-anti-VEGF tyrosine kinase inhibitor (TKI), administered via suprachoroidal injection in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Phase I/IIa, open-label, sequential dose escalation.<br><br>PARTICIPANTS: Anti-VEGF treatment-experienced patients with active subfoveal choroidal neovascularization secondary to nAMD.<br><br>METHODS: The study included 4 cohorts (0.03, 0.10, 0.50, and 1.0 mg) of approximately 5 patients each enrolled in a dose-escalating fashion. Enrolled patients received intravitreal aflibercept (2 mg) followed by a single unilateral dose of CLS-AX 1 month later. All patients were followed monthly for 3 months with the option of an additional 3 months of extended follow-up for cohorts 2 to 4. End points included systemic and ocular safety and tolerability, visual acuity, retinal thickness, and need for aflibercept therapy.<br><br>MAIN OUTCOME MEASURES: The number of patients reporting treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), changes in ophthalmic examinations, and the number of patients qualifying for additional therapy for nAMD based on protocol-defined criteria.<br><br>RESULTS: OASIS enrolled 27 patients with nAMD with mean age of 81 years, mean duration of nAMD diagnosis of 54 months, and between 5 and 90 prior anti-VEGF treatments. Twenty-six patients completed through 3 months, with 14 entering and completing the 3-month extension. No SAEs, drug-related TEAEs, or TEAEs leading to discontinuation were observed after CLS-AX administration; there were no adverse events related to ocular inflammation, vasculitis, intraocular pressure, or dispersion of drug into the vitreous or anterior chamber. Through 6 months, stable mean best-corrected visual acuity and stable mean central subfield thickness (CST) were observed, suggestive of TKI biologic effect. No aflibercept therapy was administered up to 3 months in 58% (15/26) of patients who completed 3 months of follow-up in OASIS. In the Extension, 57% (8/14) of patients went up to 6 months without receiving aflibercept therapy.<br><br>CONCLUSIONS: Up to 1.0 mg CLS-AX, a highly potent TKI targeted to the suprachoroidal space (SCS) via the SCS Microinjector, was well tolerated, with stable mean visual acuity and mean CST. A majority of patients followed for 6 months did not require aflibercept therapy.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39327941,
year = {2025},
author = {Lee, SH and Lee, MY},
title = {Full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {35},
number = {1},
pages = {NP16-NP19},
doi = {10.1177/11206721241286708},
pmid = {39327941},
issn = {1724-6016},
mesh = {Humans ; *Intravitreal Injections ; Male ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Tomography, Optical Coherence ; *Retinal Perforations/diagnosis/chemically induced/surgery ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Antibodies, Monoclonal, Humanized/adverse effects/administration &amp; dosage/therapeutic use ; *Visual Acuity ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Vitrectomy ; Fluorescein Angiography ; },
abstract = {PURPOSE: To describe a case of full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration, which has not been reported to date.<br><br>CASE DESCRIPTION: A 65-year-old male patient received brolucizumab intravitreal injection therapy for neovascular macular degeneration of the right eye. He received multiple intravitreal anti-VEGF injections on a pro re nata regimen and developed a full thickness macular hole.<br><br>OUTCOME: Surgical treatment was performed with pars plana vitrectomy of the right eye. Full thickness macular hole was successfully treated.<br><br>CONCLUSION: Although a full thickness macular hole following intravitreal brolucizumab injection is an uncommon complication, it requires caution.},
}
@article {pmid39327839,
year = {2025},
author = {Kanbay, M and Guldan, M and Ozbek, L and Copur, S and Mallamaci, F and Zoccali, C},
title = {Unveiling the intricacies of chronic kidney disease: From ocular manifestations to therapeutic frontiers.},
journal = {European journal of clinical investigation},
volume = {55},
number = {1},
pages = {e14324},
doi = {10.1111/eci.14324},
pmid = {39327839},
issn = {1365-2362},
mesh = {Humans ; Cataract/etiology/physiopathology ; *Disease Progression ; Glaucoma/physiopathology/etiology ; Macular Degeneration/etiology/physiopathology ; Optic Nerve Diseases/etiology/physiopathology ; *Renal Insufficiency, Chronic/complications/physiopathology/therapy ; Renin-Angiotensin System/physiology ; *Retinal Diseases/etiology/physiopathology/therapy ; },
abstract = {BACKGROUND: Shared anatomical, histological and physiological pathways between the kidney and the eye are well documented, demonstrating that ocular manifestations serve as valuable prognostic indicators in chronic kidney disease (CKD), providing insights into disease severity and progression. Through non-invasive imaging modalities such as retinal fundus photography, early retinal microvascular alterations indicative of CKD progression can be detected, enabling timely intervention and risk stratification. However, the conclusions drawn from the review primarily demonstrate a strong or independent association between glaucoma or retinopathy and CKD.<br><br>RESULTS AND CONCLUSION: Multiple shared pathophysiological events have been implicated in the pathogenesis in the alterations at eye and kidney including renin-angiotensin-aldosterone system. Patients with CKD are more likely to experience glaucoma, age-related macular degeneration, cataracts, uremic optic neuropathy and retinopathy. To establish the role of ocular manifestations in predicting CKD progression, it is crucial to address the limitations of correlation and explore the underlying causality with further research on common disease pathogenesis. Additionally, specific methods for risk stratification based on retinal changes, the effectiveness of timely interventions, and the development of predictive tools combining ocular and renal data are of utmost importance research topics to enlighten the bidirectional causality.},
}
@article {pmid39326776,
year = {2024},
author = {Almalki, WH and Almujri, SS},
title = {The impact of NF-κB on inflammatory and angiogenic processes in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110111},
doi = {10.1016/j.exer.2024.110111},
pmid = {39326776},
issn = {1096-0007},
mesh = {Humans ; *NF-kappa B/metabolism ; *Signal Transduction/physiology ; Inflammation/metabolism ; Neovascularization, Pathologic/metabolism ; Macular Degeneration/metabolism ; Choroidal Neovascularization/metabolism ; Animals ; Wet Macular Degeneration/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a prominent cause of vision loss, characterized by two different types, dry (atrophic) and wet (neovascular). Dry AMD is distinguished by the progressive deterioration of retinal cells, which ultimately causes a decline in vision. In contrast, wet AMD is defined by the abnormal development of blood vessels underneath the retina, leading to a sudden and severe vision impairment. The course of AMD is primarily driven by chronic inflammation and pathological angiogenesis, in which the NF-κB signaling pathway plays a crucial role. The activation of NF-κB results in the generation of pro-inflammatory cytokines, chemokines, and angiogenic factors like VEGF, which contribute to inflammation and the formation of new blood vessels in AMD. This review analyzes the intricate relationship between NF-κB signaling, inflammation, and angiogenesis in AMD and assesses the possibility of using NF-κB as a target for therapy. The evaluation involves a comprehensive examination of preclinical and clinical evidence that substantiates the effectiveness of NF-κB inhibitors in treating AMD by diminishing inflammation and pathological angiogenesis.},
}
@article {pmid39326773,
year = {2024},
author = {Zhang, XY and Han, C and Yao, Y and Wei, TT},
title = {Current insights on mitochondria-associated endoplasmic reticulum membranes (MAMs) and their significance in the pathophysiology of ocular disorders.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110110},
doi = {10.1016/j.exer.2024.110110},
pmid = {39326773},
issn = {1096-0007},
mesh = {*Mitochondria Associated Membranes/pathology/physiology ; *Eye Diseases/physiopathology ; Humans ; Animals ; },
abstract = {The intricate interaction network necessary for essential physiological functions underscores the interdependence among eukaryotic cells. Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs), specialized junctions between mitochondria and the ER, were recently discovered. These junctions participate in various cellular processes, including calcium level regulation, lipid metabolism, mitochondrial integrity maintenance, autophagy, and inflammatory responses via modulating the structure and molecular composition of various cellular components. Therefore, MAMs contribute to the pathophysiology of numerous ocular disorders, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and glaucoma. In addition to providing a concise overview of the architectural and functional aspects of MAMs, this review explores the key pathogenetic pathways involving MAMs in the development of several ocular disorders.},
}
@article {pmid39326023,
year = {2024},
author = {Nunns, B and Singh, V and Ah-Chan, J},
title = {Intravitreal therapy in neovascular age-related macular degeneration-adapting to increasing demand and changing times.},
journal = {The New Zealand medical journal},
volume = {137},
number = {1603},
pages = {129-137},
doi = {10.26635/6965.6597},
pmid = {39326023},
issn = {1175-8716},
mesh = {Humans ; *Intravitreal Injections ; Male ; Female ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *COVID-19/epidemiology ; New Zealand ; Aged, 80 and over ; Time-to-Treatment/statistics &amp; numerical data ; Macular Degeneration/drug therapy/therapy ; Wet Macular Degeneration/drug therapy ; SARS-CoV-2 ; Ranibizumab/administration &amp; dosage/therapeutic use ; },
abstract = {AIMS: To report the outcomes of patients with neovascular age-related macular degeneration (nAMD) at Palmerston North Eye Clinic (PNEC) during 2020 and 2021, comparing time to treatment initiation based on nurse-injector availability and during COVID-19 restrictions.<br><br>METHODS: Data were recorded from a prospective database for patients with nAMD at PNEC. Each patient's electronic health record was reviewed to ensure the accuracy of the database and to fill in missing data points. Statistics were done using Microsoft Excel and R.<br><br>RESULTS: One hundred and fifty-six eyes were diagnosed with nAMD during the study. Mean time from referral triage to first injection was 13.08 days across the study period. Time to treatment initiation was not statistically different by level of COVID-19 restriction but there was a significant difference in first specialist appointment to injection interval when three nurse-injectors were available compared to four. The effect seemed most evident in subsequent months after reduced nurse-injector availability began.<br><br>CONCLUSIONS: Despite an increase in nAMD diagnoses each year, PNEC continues to meet national guidelines for interval from referral to treatment initiation through innovations in practice. As demand for intravitreal injections continues to increase, further resourcing and research into newer agents will be required to keep wait times compliant with guidelines.},
}
@article {pmid39325754,
year = {2024},
author = {Peterson, KM and Mishra, S and Asaki, E and Powell, JI and He, Y and Berger, AE and Rajapakse, D and Wistow, G},
title = {Serum-deprivation response of ARPE-19 cells; expression patterns relevant to age-related macular degeneration.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0293383},
pmid = {39325754},
issn = {1932-6203},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/genetics/pathology/metabolism ; Cell Line ; Extracellular Matrix/metabolism ; Culture Media, Serum-Free/pharmacology ; Gene Expression Regulation ; Gene Expression Profiling ; Cholesterol/metabolism ; Transcriptome ; },
abstract = {ARPE-19 cells are derived from adult human retinal pigment epithelium (RPE). The response of these cells to the stress of serum deprivation mimics some important processes relevant to age-related macular degeneration (AMD). Here we extend the characterization of this response using RNASeq and EGSEA gene set analysis of ARPE-19 cells over nine days of serum deprivation. This experiment confirmed the up-regulation of cholesterol and lipid-associated pathways that increase cholesterol levels in these cells. The gene expression analysis also identified other pathways relevant to AMD progression. There were significant changes in extracellular matrix gene expression, notably a switch from expression of collagen IV, a key component of Bruch's membrane (part of the blood-retina barrier), to expression of a fibrosis-like collagen type I matrix. Changes in the expression profile of the extracellular matrix led to the discovery that amelotin is induced in AMD and is associated with the development of the calcium deposits seen in late-stage geographic atrophy. The transcriptional profiles of other pathways, including inflammation, complement, and coagulation, were also modified, consistent with immune response patterns seen in AMD. As previously noted, the cells resist apoptosis and autophagy but instead initiate a gene expression pattern characteristic of senescence, consistent with the maintenance of barrier function even as other aspects of RPE function are compromised. Other differentially regulated genes were identified that open new avenues for investigation. Our results suggest that ARPE-19 cells maintain significant stress responses characteristic of native RPE that are informative for AMD. As such, they provide a convenient system for discovery and for testing potential therapeutic interventions.},
}
@article {pmid39325472,
year = {2024},
author = {Connolly, E and El-Farouki, G and Brennan, K and Cahill, M and Doyle, SL},
title = {Poor Response to Bevacizumab Correlates With Higher IL-6 and IL-8 Aqueous Cytokines in AMD.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {11},
pages = {37},
pmid = {39325472},
issn = {1552-5783},
mesh = {Humans ; *Bevacizumab/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Intravitreal Injections ; Male ; Female ; Aged ; *Tomography, Optical Coherence ; *Interleukin-6/metabolism ; *Aqueous Humor/metabolism ; *Interleukin-8/metabolism ; Wet Macular Degeneration/drug therapy/metabolism/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Aged, 80 and over ; Prospective Studies ; Middle Aged ; Visual Acuity/physiology ; Macular Degeneration/drug therapy/metabolism/diagnosis ; Treatment Outcome ; },
abstract = {PURPOSE: To evaluate the effect of intravitreal bevacizumab on aqueous levels of a panel of 12 inflammatory cytokines in patients with neovascular age-related macular degeneration (nAMD) and correlate response to treatment, as measured by change in the central subfovea thickness (CST), with cytokine levels.<br><br>METHODS: Thirty-three treatment-na&#xef;ve patients with nAMD received a loading dose of intravitreal bevacizumab consisting of three injections at six weekly intervals. The aqueous samples prior to the first (baseline), second (week 6), and third (week 12) injections were analyzed for cytokine levels. Participants were subgrouped based on changes in CST on spectral-domain optical coherence tomography (SD-OCT) at 12&#xa0;weeks. Group 1 included patients with a decrease in CST (responders; n = 27). Group 2 included patients who had no decrease in CST (poor responders; n = 6).<br><br>RESULTS: Aqueous IL-8 was the only cytokine to demonstrate a significant difference in levels between responders and poor responders, with higher interleukin-8 (IL-8) at week 12 in the poor responder group. Aqueous IL-6 and IL-8 levels showed a positive correlation with CST on SD-OCT (Spearman r = 0.45 and 0.55, respectively). There was a temporal increase overall in cytokine concentration accompanying bevacizumab treatment.<br><br>CONCLUSIONS: Aqueous IL-6 and IL-8 may be important markers of treatment response or poor response in nAMD. Future therapeutic strategies may include targeted treatment against both vascular endothelial cell growth factor (VEGF) and IL-6 and/or IL-8 in patients who do not respond to anti-VEGF treatment alone.},
}
@article {pmid39324773,
year = {2024},
author = {Ni, QY and Wu, MY and Zha, CK and Wen, Y and Zhong, L and Ding, JJ and Li, XY and Tao, LM and Jiang, ZX and Cao, F},
title = {Trend and driving factors in burden of age-related macular degeneration in older adults aged 60-89 years: a global analysis over three decades.},
journal = {Age and ageing},
volume = {53},
number = {9},
pages = {},
doi = {10.1093/ageing/afae207},
pmid = {39324773},
issn = {1468-2834},
support = {2023AH020046//Natural Science Funds for Distinguished Young Scholar of Anhui Province/ ; 82171043//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Aged ; *Macular Degeneration/epidemiology/diagnosis ; Male ; Aged, 80 and over ; Female ; Prevalence ; Middle Aged ; *Global Health/statistics &amp; numerical data ; Age Factors ; Risk Factors ; Cost of Illness ; Time Factors ; },
abstract = {BACKGROUND: To explore temporal trends and determine driving factors of age-related macular degeneration (AMD) burden in older adults aged 60-89 years at global, regional and national levels from 1990 to 2019.<br><br>METHODS: Prevalence and years lived with disability (YLDs) were extracted. Joinpoint regression analysis was adopted to calculate average annual percentage change and to identify the year with the most significant changes. Global trends were stratified by sex, age and sociodemographic index, and regional and national trends were explored. Decomposition analysis was conducted to determine what extent the forces of population size, age structure and epidemiologic change driving alterations of AMD burden.<br><br>RESULTS: Globally, prevalence rate slightly increased whereas YLDs rate decreased. The year 2005 marked a turning point where both prevalence and YLDs started to decline. Regionally, Western Sub-Saharan Africa had the highest prevalence and YLDs rates in 2019, with East Asia experiencing the most notable rise in prevalence from 1990 to 2019. Global decomposition revealed that the increased case number was primarily driven by population growth and ageing, and epidemiological change was only detected to lessen but far from offset these impacts.<br><br>CONCLUSIONS: Although there was only slight increase or even decrease in prevalence and YLDs rates of AMD in older adults, the case number still nearly doubled, which may be primarily attributed to population growth and ageing, coupled with the emerging growing pattern of prevalence rate from 2015, collectively suggesting a huge challenge in control and management of AMD.},
}
@article {pmid39324238,
year = {2024},
author = {Grunin, M and Igo, RP and Song, YE and Blanton, SH and Pericak-Vance, MA and Haines, JL and , },
title = {Identifying X-chromosome variants associated with age-related macular degeneration.},
journal = {Human molecular genetics},
volume = {33},
number = {24},
pages = {2085-2093},
pmid = {39324238},
issn = {1460-2083},
support = {R01 EY022310/EY/NEI NIH HHS/United States ; 1X01HG006934-01/GF/NIH HHS/United States ; M2021006F//Bright Focus Fellowship for Macular Degeneration/ ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Chromosomes, Human, X/genetics ; *Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Genotype ; *Macular Degeneration/genetics ; *Polymorphism, Single Nucleotide ; White/genetics ; },
abstract = {PURPOSE: In genome-wide association studies (GWAS), X chromosome (ChrX) variants are often not investigated. Sex-specific effects and ChrX-specific quality control (QC) are needed to examine these effects. Previous GWAS identified 52 autosomal variants associated with age-related macular degeneration (AMD) via the International AMD Genomics Consortium (IAMDGC), but did not analyze ChrX. Therefore¸ our goal was to investigate ChrX variants for association with AMD.<br><br>METHODS: We genotyped 29&#x2009;629 non-Hispanic White (NHW) individuals (M/F:10404/18865; AMD12,087/14723) via a custom chip and imputed after ChrX-specific QC (XWAS 3.0) using the Michigan Imputation Server. Imputation generated 1&#x2009;221&#x2009;623 variants on ChrX. Age, informative PCs, and subphenotypes were covariates for logistic association analyses with Fisher's correction. Gene/pathway analyses were performed with VEGAS, GSEASNP, ICSNPathway, DAVID, and mirPath.<br><br>RESULTS: Logistic association on NHW individuals with sex correction identified variants in/near the genes SLITRK4, ARHGAP6, FGF13 and DMD associated with AMD (P&#xa0;<&#x2009;1&#xa0;&#xd7;&#xa0;10-6,Fisher's combined-corrected). Association testing of the subphenotypes of choroidal neovascularization and geographic atrophy (GA), identified variants in DMD associated with GA (P&#xa0;<&#x2009;1&#xa0;&#xd7;&#xa0;10-6, Fisher's combined-corrected). Via gene-based analysis with VEGAS, several genes were associated with AMD (P&#xa0;<&#x2009;0.05, both truncated tail strength/truncated product P) including SLITRK4 and BHLHB9. Pathway analysis using GSEASNP and DAVID identified genes associated with nervous system development (FDR: P:0.02), and blood coagulation (FDR: P:0.03). Variants in the region of a microRNA (miR) were associated with AMD (P&#xa0;<&#x2009;0.05, truncated tail strength/truncated product P). Via DIANA mirPath analysis, downstream targets of miRs showed association with brain disorders and fatty acid elongation (P&#xa0;<&#x2009;0.05). A long noncoding RNA on ChrX near the DMD locus was also associated with AMD (P&#xa0;=&#x2009;4&#xa0;&#xd7;&#xa0;10-7). Epistatic analysis (t-statistic) for a quantitative trait of AMD vs control including covariates found a suggestive association in the XG gene (P&#xa0;=&#x2009;2&#xa0;&#xd7;&#xa0;10^-5).<br><br>CONCLUSIONS: Analysis of ChrX variation identifies several potential new locifor AMD risk and these variants nominate novel AMD pathways. Further analysis is needed to refine these results and to understand their biological significance and relationship with AMD development in worldwide populations.},
}
@article {pmid39324131,
year = {2024},
author = {Li, Z and Huang, J and Chen, J and Zeng, J and Jiang, H and Ding, L and Zhang, T and Sun, W and Lu, R and Zhang, Q and Liang, L},
title = {A deep-learning pipeline for the diagnosis and grading of common blinding ophthalmic diseases based on lesion-focused classification model.},
journal = {Frontiers in artificial intelligence},
volume = {7},
number = {},
pages = {1444136},
pmid = {39324131},
issn = {2624-8212},
abstract = {BACKGROUND: Glaucoma (GLAU), Age-related Macular Degeneration (AMD), Retinal Vein Occlusion (RVO), and Diabetic Retinopathy (DR) are common blinding ophthalmic diseases worldwide.<br><br>PURPOSE: This approach is expected to enhance the early detection and treatment of common blinding ophthalmic diseases, contributing to the reduction of individual and economic burdens associated with these conditions.<br><br>METHODS: We propose an effective deep-learning pipeline that combine both segmentation model and classification model for diagnosis and grading of four common blinding ophthalmic diseases and normal retinal fundus.<br><br>RESULTS: In total, 102,786 fundus images of 75,682 individuals were used for training validation and external validation purposes. We test our model on internal validation data set, the micro Area Under the Receiver Operating Characteristic curve (AUROC) of which reached 0.995. Then, we fine-tuned the diagnosis model to classify each of the four disease into early and late stage, respectively, which achieved AUROCs of 0.597 (GL), 0.877 (AMD), 0.972 (RVO), and 0.961 (DR) respectively. To test the generalization of our model, we conducted two external validation experiments on Neimeng and Guangxi cohort, all of which maintained high accuracy.<br><br>CONCLUSION: Our algorithm demonstrates accurate artificial intelligence diagnosis pipeline for common blinding ophthalmic diseases based on Lesion-Focused fundus that overcomes the low-accuracy of the traditional classification method that based on raw retinal images, which has good generalization ability on diverse cases in different regions.},
}
@article {pmid39322853,
year = {2025},
author = {Quist, SW and Nab, H and Postma, M and Amarakoon, S and van Asten, F and Freriks, R},
title = {A cost-minimization analysis of anti-VEGFs for the treatment of neovascular age-related macular degeneration in the Netherlands.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {2},
pages = {327-345},
pmid = {39322853},
issn = {1435-702X},
mesh = {Humans ; Netherlands/epidemiology ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage/economics ; *Recombinant Fusion Proteins/administration &amp; dosage/economics ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/economics/epidemiology ; Ranibizumab/administration &amp; dosage/economics ; Bevacizumab/economics/administration &amp; dosage ; Drug Costs ; *Health Care Costs ; },
abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is the main cause of severe vision loss globally. Neovascular AMD (nAMD) is an advanced stage of AMD treated with anti-vascular endothelial growth factors (anti-VEGFs). Although anti-VEGF treatment is effective, the frequent intravitreal injections place a burden on patients, (in)formal caregivers, and clinics. This study assesses the health-economic impact of anti-VEGF agents with lower injection frequency that have the potential to reduce treatment burden and compares it to the standard of care.<br><br>METHODS: We developed a cost-minimization model to evaluate the direct medical costs associated with first-line unilateral anti-VEGF treatment across a 3-year time horizon in the Netherlands. The analysis compared aflibercept 8&#xa0;mg, aflibercept 2&#xa0;mg, bevacizumab, faricimab, and ranibizumab. Our model adopted a treat-and-extend (T&amp;E) regimen for aflibercept 2&#xa0;mg, bevacizumab, and ranibizumab. For aflibercept 8&#xa0;mg, a flexible regimen that was extendable up to 24&#xa0;weeks was applied, while faricimab followed a flexible regimen that was extendable up to 16&#xa0;weeks. Additionally, since list prices may vary from net prices, we calculated the break-even price for each anti-VEGF in comparison to bevacizumab, which is the recommended first-line treatment due to its low medication price.<br><br>RESULTS: Based on list prices, aflibercept 8&#xa0;mg led to the lowest treatment costs (&#x20ac;16,251 per patient over a 3-year time horizon), closely followed by bevacizumab (&#x20ac;17,616 per patient over a 3-year time horizon). Ranibizumab led to the highest per-patient costs (&#x20ac;31,746 over a 3-year time horizon). For bevacizumab, most costs were attributable to administration, while for the other anti-VEGFs, most were attributable to medication. Aflibercept 8&#xa0;mg is cost-saving compared to bevacizumab at their medication prices at the time of writing. Aflibercept 2&#xa0;mg, faricimab, and ranibizumab should be priced below &#x20ac;488, &#x20ac;591, and &#x20ac;75, respectively. To be cost-equal to bevacizumab with current list prices, anti-VEGFs should be administered with a maximum of 12.7 to 13.8 injections over a 3-year time horizon.<br><br>CONCLUSION: According to the injection frequency observed in clinical trials, aflibercept 8&#xa0;mg would be the anti-VEGF that generates the lowest per-patient healthcare costs for the treatment of nAMD in the Netherlands after a treatment period of three years. Our study indicates that anti-VEGF drugs with a lower injection frequency might provide a cost-saving solution to the increasing burden of anti-VEGF treatment on the healthcare system.},
}
@article {pmid39322793,
year = {2024},
author = {Li, M and Li, W and Wang, X and Wu, G and Du, J and Xu, G and Duan, M and Yu, X and Cui, C and Liu, C and Fu, Z and Yu, C and Wang, L},
title = {Identification and Activity Study of an Impurity Band Observed in the nrSDS-PAGE of Aflibercept.},
journal = {Pharmaceutical research},
volume = {41},
number = {10},
pages = {2031-2042},
pmid = {39322793},
issn = {1573-904X},
support = {2021YFF0600804-C02-05//National Key Research and Development Program/ ; },
mesh = {*Receptors, Vascular Endothelial Growth Factor/chemistry ; *Recombinant Fusion Proteins/chemistry/genetics ; Humans ; *Electrophoresis, Polyacrylamide Gel/methods ; Vascular Endothelial Growth Factor A ; Tandem Mass Spectrometry/methods ; Drug Contamination/prevention &amp; control ; Angiogenesis Inhibitors/chemistry/pharmacology ; Macular Degeneration/drug therapy ; Chromatography, Liquid/methods ; Peptide Mapping/methods ; Macular Edema/drug therapy ; },
abstract = {BACKGROUND: Aflibercept is a biopharmaceutical targeting vascular endothelial growth factor (VEGF) that has shown promise in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in adults. Quality control studies of aflibercept employing non-reduced SDS-PAGE (nrSDS-PAGE) have shown that a significant variant band (IM1) is consistently present below the main band. Considering the quality control strategy of biopharmaceuticals, structural elucidation and functional studies are required.<br><br>METHODS: In this study, the variant bands in nrSDS-PAGE were collected through electroelution and identified by peptide mass fingerprinting based on liquid chromatography-tandem MS (LC-MS/MS). This variant was expressed using knob-into-hole (KIH) design transient transfection for the detection of ligand affinity, binding activity and biological activity.<br><br>RESULTS: The variant band was formed by C-terminal truncation at position N99 of one chain in the aflibercept homodimer. Then, this variant was successfully expressed using KIH design transient transfection. The ligand affinity of the IM1 truncated variant was reduced by 18-fold, and neither binding activity nor biological activity were detected.<br><br>CONCLUSIONS: The efficacy of aflibercept is influenced by the loss of biological activity of the variant. Therefore, this study supports the development of a quality control strategy for aflibercept.},
}
@article {pmid39319643,
year = {2025},
author = {Lenhof, S and Kodjikian, L and Gascon, P and Gadiollet, E and Feldman, A and De Bats, F and Wolff, B and Pradat, P and Mathis, T},
title = {Subretinal fibrosis occurrence according to macular neovascularisation subtypes in neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {103},
number = {2},
pages = {e104-e117},
doi = {10.1111/aos.16759},
pmid = {39319643},
issn = {1755-3768},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Angiogenesis Inhibitors ; Fibrosis/epidemiology/etiology/diagnosis ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Incidence ; *Macula Lutea/pathology ; *Retina/pathology ; Retrospective Studies ; Risk Factors ; *Tomography, Optical Coherence/methods ; *Visual Acuity ; *Wet Macular Degeneration/diagnosis/complications ; Cohort Studies ; },
abstract = {PURPOSE: To assess subretinal fibrosis (SF) occurrence in neovascular age-related macular degeneration (nAMD), according to macular neovascularisation (MNV) subtypes.<br><br>METHODS: A Retrospective national multi centre cohort study included eyes with naive nAMD. Main outcome measures were, according to MNV subtypes, cumulative incidence for SF, risk factors, and best corrected visual acuity (BCVA) for 36&#x2009;months.<br><br>RESULTS: Four hundred and twenty eyes were included. Cumulative incidence of SF was 34.3% at 1&#x2009;year, 39.0% at 2&#x2009;years and 50.6% at 3&#x2009;years. In multivariable analysis, Type 2 and mixed type 1 and 2 MNV were associated (p&#x2009;<&#x2009;0.001) with a more frequent and rapid development of SF (respectively 85.5% and 81.0% at 1&#x2009;year, then 95.8% and 93.1% at 3&#x2009;years) than Types 1 and 3 (respectively 11.3% and 3.6% at 1&#x2009;year, then 22.9% and 12.7% at 3&#x2009;years). In Type 2 and mixed type 1 and 2 MNV combined, at baseline a worse BCVA (p&#x2009;=&#x2009;0.02) and a higher maximal subretinal hyperreflective material (SHRM) thickness (p&#x2009;=&#x2009;0.005) were associated with SF development at 3&#x2009;years. In Type 1 MNV, the presence at baseline of intraretinal fluid (IRF) (p&#x2009;=&#x2009;0.007) or SHRM (p&#x2009;<&#x2009;0.001) and a higher percentage of visits with IRF (p&#x2009;<&#x2009;0.001) or with SHRM (p&#x2009;<&#x2009;0.001) were associated with SF occurrence. For Type 3 MNV, only a higher percentage of visits with SHRM (p&#x2009;=&#x2009;0.001) was associated with SF. Including all MNV subtypes, eyes with a worse BCVA at baseline were associated with SF development (p&#x2009;<&#x2009;0.001). Conversely, presence of SF at 3&#x2009;years was associated with a worse baseline BCVA (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Occurrence of SF differs when considering apart MNV subtypes.},
}
@article {pmid39318989,
year = {2024},
author = {Wykoff, CC and Kuppermann, BD and Regillo, CD and Chang, M and Hariprasad, SM and Duker, JS and Altaf, S and Saïm, S},
title = {Extended Intraocular Drug-Delivery Platforms for the Treatment of Retinal and Choroidal Diseases.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {5},
pages = {577-586},
pmid = {39318989},
issn = {2474-1272},
abstract = {Purpose: To review sustained-release intraocular platforms used to treat diseases of the retina and choroid. Methods: A literature review of the current applications of biomaterials for sustained-release therapy in retinal and choroidal diseases was performed. Results: Retinal and choroidal diseases, such as neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), and uveitis, are commonly treated using intravitreal (IVT) therapies that require frequent IVT injections. Multiple sustained-release options for IVT therapy have been approved by the US Food and Drug Administration for the treatment of inflammatory eye diseases, including noninfectious uveitis, infectious diseases, and exudative retinal diseases (eg, retinal venous occlusive disease and DME) using drugs such as fluocinolone acetonide, ganciclovir, and dexamethasone. The platforms for these drugs are biodegradable or nonbiodegradable. They use biomaterials such as polymers and hydrogels and are typically implanted surgically or injected into the vitreous, where they release the drug gradually over months or years. Building on these technologies, novel platforms are being studied that are intended to treat conditions including nAMD, DR, DME, and uveitis. These platforms are being tested for their safety, efficacy, and ability to reduce the injection and visit burden. Conclusions: Multiple sustained-release ocular drug-delivery platforms are currently commercially available, and many new sustained-release IVT platforms are being investigated. The hope is that meaningfully reducing the injection burden by extending intervals between treatments while maintaining optimal efficacy will improve long-term outcomes.},
}
@article {pmid39318981,
year = {2024},
author = {Burgett, L and Aggarwal, N and Latona, J and Driban, M and Chhablani, J and Maturi, RK},
title = {Retrospective Large Database Study of Central Serous Chorioretinopathy Treatments and Visual Outcomes Analysis in the United States.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {5},
pages = {508-516},
pmid = {39318981},
issn = {2474-1272},
abstract = {Purpose: To evaluate a large database detailing the changes in visual acuity (VA) and central subfield thickness after various treatments for central serous chorioretinopathy (CSCR). Methods: A retrospective analysis was performed of patients with CSCR from January 2015 to September 2022 using the Vestrum Health Retina Database of aggregated de-identified electronic medical records from retina specialists in the United States. The cases of CSCR were categorized by age, sex, and treatment provided. Results: The annual incidence of CSCR was 1.72% (61 755 of 3 598 672 patient eyes), with a mean patient age of 53 years. Male eyes comprised 71.8% of the patient population. Eighty-five percent of patients received no treatment within 1 year of diagnosis. Of the patients needing treatment, 21% received thermal laser therapy, 23% photodynamic therapy, and 49% antivascular endothelial growth factor (anti-VEGF) intraocular injection. Patients not receiving treatment had the best baseline and 1-year VA. All treatment groups had an increased percentage of patients gaining letters compared with patients not receiving treatment. Conclusions: Although most patients did not require treatment, those who received treatment generally did well, with a large proportion having visual gain. Statistical analysis suggests treatment has a positive impact on VA outcomes. Patients receiving combination treatment were older and had the least visual gain of the treated cohorts. Younger patients with CSCR treated with anti-VEGF (and without a secondary diagnosis of macular degeneration) had the greatest increase in VA at 1 year.},
}
@article {pmid39318978,
year = {2024},
author = {Siddiqui, MZ and Durrani, A and Smith, BT},
title = {Faricimab-Associated Retinal Vasculitis.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {5},
pages = {627-630},
pmid = {39318978},
issn = {2474-1272},
abstract = {Purpose: To report a case of retinal vasculitis after intravitreal faricimab-svoa injection. Methods: A case and its management were reviewed. Results: A 77-year-old woman presented with a painless decrease in visual acuity (VA) to counting fingers after receiving an intravitreal faricimab-svoa injection for neovascular age-related macular degeneration. An examination showed an anterior chamber reaction without hypopyon. Vitritis was present with numerous scattered retinal hemorrhages. Fluorescein angiography showed delayed filling with extensive vascular leakage consistent with nonocclusive vasculitis. The patient was immediately treated with intravenous steroids, resulting in rapid improvement and recovery of her 20/40 baseline VA. The vasculitis resolved without occlusion. Conclusions: Faricimab-svoa can be associated with significant vasculitis. Prompt treatment with intravenous steroids can be beneficial in the recovery of sight.},
}
@article {pmid39318977,
year = {2024},
author = {Valikodath, NG and Li, JD and Raynor, W and Izatt, JA and Toth, CA and Vajzovic, L},
title = {Intraoperative OCT-Guided Volumetric Measurements of Subretinal Therapy Delivery in Humans.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {5},
pages = {587-592},
pmid = {39318977},
issn = {2474-1272},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; U01 EY028079/EY/NEI NIH HHS/United States ; },
abstract = {Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT-measured subretinal tPA volume: Patient 1, 130 µL from syringe, 118 µL based on intraoperative OCT, 9% difference; Patient 2, 140 µL, 50 µL, 64%; Patient 3, 110 µL, 122 µL, 11%. The total bleb surface area was 129 mm[2] in Patient 1, 55 mm[2] in Patient 2, and 106 mm[2] in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image-based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT-obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery.},
}
@article {pmid39318709,
year = {2025},
author = {Herrera, G and Shen, M and Trivizki, O and Liu, J and Shi, Y and Hiya, FE and Li, J and Cheng, Y and Lu, J and Zhang, Q and O'Brien, RC and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Comparison between Spectral-Domain and Swept-Source OCT Angiography for the Measurement of Persistent Hypertransmission Defects in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {5},
number = {1},
pages = {100593},
pmid = {39318709},
issn = {2666-9145},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs).<br><br>DESIGN: Retrospective study.<br><br>PARTICIPANTS: Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD).<br><br>METHODS: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6&#xa0;&#xd7; 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension &#x2265;250 &#x3bc;m on the en face images generated using a slab extending from 64 to 400 &#x3bc;m beneath Bruch's membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method.<br><br>MAIN OUTCOME MEASURES: The mean sqrt area measurements and the number of hyperTDs were compared.<br><br>RESULTS: The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc&#xa0;= 0.969 and rc&#xa0;= 0.999, respectively). The mean number of hyperTDs was 4.3 &#xb1; 3.1 for SD-OCTA scans and 4.5 &#xb1; 3.3 for SS-OCTA scans (P&#xa0;= 0.06). The mean sqrt total area measurements were 1.16 &#xb1; 0.64 mm for the SD-OCTA scans and 1.17 &#xb1; 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant.<br><br>CONCLUSIONS: Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39316206,
year = {2024},
author = {Makin, RD and Apicella, I and Dholkawala, R and Fukuda, S and Hirahara, S and Hirano, Y and Kim, Y and Nagasaka, A and Nagasaka, Y and Narendran, S and Pereira, F and Varshney, A and Wang, SB and Ambati, J and Gelfand, BD},
title = {Inflammasome activation aggravates choroidal neovascularization.},
journal = {Angiogenesis},
volume = {27},
number = {4},
pages = {919-929},
pmid = {39316206},
issn = {1573-7209},
support = {R01 EY032512/EY/NEI NIH HHS/United States ; R01 EY031039/EY/NEI NIH HHS/United States ; R01AG082108/AG/NIA NIH HHS/United States ; R01 AG078892/AG/NIA NIH HHS/United States ; R01 EY028027/EY/NEI NIH HHS/United States ; R01HL164592/HL/NHLBI NIH HHS/United States ; R01EY031039/EY/NEI NIH HHS/United States ; R01 HL164592/HL/NHLBI NIH HHS/United States ; },
mesh = {*Choroidal Neovascularization/pathology/metabolism/genetics ; Animals ; *Inflammasomes/metabolism ; Mice ; *Mice, Inbred C57BL ; *Mice, Knockout ; Macrophages/metabolism/pathology ; Interleukin-1beta/metabolism ; Alu Elements/genetics ; Caspase 1/metabolism ; Amyloid beta-Peptides/metabolism ; },
abstract = {Inflammasome activation is implicated in diseases of aberrant angiogenesis such as age-related macular degeneration (AMD), though its precise role in choroidal neovascularization (CNV), a characteristic pathology of advanced AMD, is ill-defined. Reports on inhibition of inflammasome constituents on CNV are variable and the precise role of inflammasome in mediating pathological angiogenesis is unclear. Historically, subretinal injection of inflammasome agonists alone has been used to investigate retinal pigmented epithelium (RPE) degeneration, while the laser photocoagulation model has been used to study pathological angiogenesis in a model of CNV. Here, we report that the simultaneous introduction of any of several disease-relevant inflammasome agonists (Alu or B2 RNA, Alu cDNA, or oligomerized amyloid β (1-40)) exacerbates laser-induced CNV. These activities were diminished or abrogated by genetic or pharmacological targeting of inflammasome signaling constituents including P2rx7, Nlrp3, caspase-1, caspase-11, and Myd88, as well as in myeloid-specific caspase-1 knockout mice. Alu RNA treatment induced inflammasome activation in macrophages within the CNV lesion, and increased accumulation of macrophages in an inflammasome-dependent manner. Finally, IL-1β neutralization prevented inflammasome agonist-induced chemotaxis, macrophage trafficking, and angiogenesis. Collectively, these observations support a model wherein inflammasome stimulation promotes and exacerbates CNV and may be a therapeutic target for diseases of angiogenesis such as neovascular AMD.},
}
@article {pmid39314940,
year = {2024},
author = {Kumar, H and Bagdasarova, Y and Song, S and Hickey, DG and Cohn, AC and Okada, M and Finger, RP and Terheyden, JH and Hogg, RE and Gabrielle, PH and Arnould, L and Jannaud, M and Hadoux, X and van Wijngaarden, P and Abbott, CJ and Hodgson, LAB and Schwartz, R and Tufail, A and Chew, EY and Lee, CS and Fletcher, EL and Bahlo, M and Ansell, BRE and Pébay, A and Guymer, RH and Lee, AY and Wu, Z},
title = {Deep Learning-Based Detection of Reticular Pseudodrusen in Age-Related Macular Degeneration on Optical Coherence Tomography.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.09.11.24312817},
pmid = {39314940},
abstract = {Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). Their detection is paramount in the clinical management of those with AMD, yet they remain challenging to reliably identify. We thus developed a deep learning (DL) model to segment RPD from 9,800 optical coherence tomography B-scans, and this model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC]=0·76 [95% confidence interval [CI] 0·71-0·81]) than the agreement amongst the specialists (DSC=0·68, 95% CI=0·63-0·73; p <0·001). In five external test datasets consisting of 1,017 eyes from 812 individuals, the DL model detected RPD with a similar level of performance as two retinal specialists (area-under-the-curve of 0·94 [95% CI=0·92-0·97], 0·95 [95% CI=0·92-0·97] and 0·96 [95% CI=0·94-0·98] respectively; p ≥0·32). This DL model enables the automatic detection and quantification of RPD with expert-level performance, which we have made publicly available.},
}
@article {pmid39311549,
year = {2025},
author = {Lee, AM and Xu, TT and Starr, MR},
title = {Trends in Research Payments for Age-related Macular Degeneration From 2015 to 2021.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {2},
pages = {95-100},
doi = {10.3928/23258160-20240903-01},
pmid = {39311549},
issn = {2325-8179},
mesh = {Humans ; *Macular Degeneration/economics ; Male ; Female ; *Biomedical Research/economics/trends ; United States ; *Research Support as Topic/economics/trends ; },
abstract = {OBJECTIVE: This study aimed to evaluate characteristics of industry and public research payments for age-related macular degeneration studies.<br><br>MATERIALS AND METHODS: Studies involving "age-related macular degeneration" or "AMD" from 2015 to 2021 were extracted from the Open Payments Database and the National Eye Institute RePORTER tool and compared to each other.<br><br>RESULTS: From 2015 to 2021, 620 ophthalmologists received $178,394,734.09 in industry research payments with a 76.9% increase from 2015 to 2020 and a subsequent 40.7% decrease in 2021. There were 84 female industry funding recipients (13.7%) compared to 528 (86.3%) male recipients (P < 0.001). For public funding, 119 ophthalmologists received $157,319,575.00 with a 31.0% increase from 2015 to 2021. Among 119 principal investigators, 37 (31.1%) were women and 82 (68.9%) were men (P = 0.05).<br><br>CONCLUSION: Industry-funded and publicly funded age-related macular degeneration-related research payments overall increased from 2015 to 2021. Funding distribution by sex trended towards male recipients. [Ophthalmic Surg Lasers Imaging Retina 2025;56:95-100.].},
}
@article {pmid39306616,
year = {2024},
author = {Puzo, M and Calvo-Perez, P and Bartol-Puyal, F and Sanchez-Monroy, J and Martin-Pinardel, R and Parrado-Carrillo, A and Moll-Udina, A and Bernal-Morales, C and Sanchez-Vela, L and Sararols-Ramsay, L and Garay-Aramburu, G and Arruabarrena, C and García-Arumí, J and Abraldes, M and Ruiz-Moreno, JM and Valldeperas, X and Velázquez-Villoria, D and Escobar-Barranco, JJ and Gallego-Pinazo, R and Figueroa, MS and Figueras-Roca, M and Barthelmes, D and Gillies, MC and Casaroli-Marano, RP and Zarranz-Ventura, J and , },
title = {Fight Retinal Blindness SPAIN. Report 3: clinical outcomes of vascular endothelial growth factor inhibitors in low vision eyes with neovascular age-related macular degeneration. A national database study.},
journal = {Eye (London, England)},
volume = {38},
number = {18},
pages = {3450-3458},
pmid = {39306616},
issn = {1476-5454},
mesh = {Humans ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Intravitreal Injections ; Female ; Male ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/physiopathology ; Aged ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Databases, Factual ; Aged, 80 and over ; *Vision, Low/physiopathology ; Spain ; Bevacizumab/therapeutic use/administration &amp; dosage ; Treatment Outcome ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/antagonists &amp; inhibitors/administration &amp; dosage ; Retrospective Studies ; },
abstract = {OBJECTIVES: To compare visual outcomes for low vision eyes (LVE) (<35 letters LogMAR or <20/200 Snellen) versus non-low vision eyes (NLVE) (>35 letters LogMAR or >20/200 Snellen) at the time of the first injection in a clinical practice setting.<br><br>METHODS: Subgroup analysis of a multicenter national database of treatment- na&#xef;ve eyes neovascular age related macular degeneration (nAMD) treated with anti-VEGF intravitreal injections divided into LVE and NLVE. Demographics, visual acuity (VA) at baseline and subsequent timepoints (12, 24, and 36 months), number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!).<br><br>RESULTS: 3138 eyes were included, 705 LVE and 2433 NLVE. The LVE group had the greatest VA gain (p&#x2009;<&#x2009;0.001), at 12, 24, and 36 months (+15, +15, and +13 letters respectively). The proportion of patients with VA loss (-5 letters) differed between groups at 12, 24, and 36 and was significantly greater (p&#x2009;<&#x2009;0.001) in NLVE. The proportion of patients with VA gain (+5 letters) was significantly higher (p&#x2009;<&#x2009;0.001) in LVE in all timeframes. The proportions of LVE that still had VA&#x2009;&#x2264;&#x2009;35 letters at 12, 24, and 36 months were 54%, 54%, and 57%. Conversely, 8%, 9%, and 8% of LVE achieved VA&#x2009;&#x2265;&#x2009;70 letters at 12, 24, and 36 months. LVE received fewer intravitreal injections than NLVE throughout follow-up (6, 9, 12 vs 7, 11, 15).<br><br>CONCLUSION: Findings of this study support the need for ongoing therapy in patients with initial visual acuity less than 35 letters since sustained visual improvements can be achieved and maintained for the first 3 years of treatment.},
}
@article {pmid39304740,
year = {2024},
author = {Valsecchi, N and Shah, S and Zarnegar, A and Tang, A and Yagobian, S and Fontana, L and Iannetta, D and Chhablani, J},
title = {Assessment of optical coherence tomography biomarkers in patients with non-neovascular age-related macular degeneration (AMD) converting to exudative AMD according to the status of the fellow eye.},
journal = {Eye (London, England)},
volume = {38},
number = {18},
pages = {3532-3538},
pmid = {39304740},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Retrospective Studies ; Aged ; *Wet Macular Degeneration/diagnosis/physiopathology ; *Visual Acuity/physiology ; Aged, 80 and over ; *Biomarkers ; Disease Progression ; Choroid/pathology/diagnostic imaging ; Fluorescein Angiography/methods ; Macula Lutea/pathology/diagnostic imaging ; },
abstract = {OBJECTIVES: To compare optical coherence tomography (OCT) biomarkers in eyes converting from non-neovascular (nnAMD) to exudative age-related macular degeneration (eAMD) based on the status of fellow eye.<br><br>METHODS: Retrospective analysis of one year of pre-conversion data of fellow eyes of patients with nnAMD and eAMD which converted to eAMD, defined as converting eyes (CE) with fellow nnAMD and CE with fellow eAMD respectively. Demographics, best corrected visual acuity (BCVA), and OCT biomarkers including drusen type, iRORA/cRORA, subfoveal ellipsoid zone (SFEZ) disruption, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), Haller vascular thickness (HVT) were evaluated. Chi-square and t-tests were employed, confidence interval of 95% and p&#x2009;<&#x2009;0.05.<br><br>RESULTS: 72 eyes of 72 patients were included: 31 CE with fellow nnAMD and 41 CE with fellow eAMD. Mean age was 81.8&#x2009;&#xb1;&#x2009;9.9 years, with 62.5% females. Subfoveal iRORA was more frequent in CE with fellow nnAMD (26%) compared to CE with fellow eAMD (6%) 44 weeks before conversion (p&#x2009;=&#x2009;0.058). SFCT and HVT were higher in CE with fellow nnAMD compared to CE with fellow eAMD 19 weeks prior to conversion (213&#x2009;&#xb1;&#x2009;82 vs. 174&#x2009;&#xb1;&#x2009;63&#x2009;&#xb5;m, p&#x2009;=&#x2009;0.052; 121&#x2009;&#xb1;&#x2009;44 vs. 104&#x2009;&#xb1;&#x2009;50&#x2009;&#xb5;m, p&#x2009;=&#x2009;0.084 respectively). BCVA was significantly higher in CE with fellow eAMD compared to CE with fellow nnAMD every time frame (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: Although subtle distinctions, no significant differences were observed between the groups. Further research is needed to understand the influence of one eye's status on progression from nnAMD to eAMD in fellow eye.},
}
@article {pmid39303841,
year = {2024},
author = {Tawarayama, H and Uchida, K and Hasegawa, H and Yoshida, M and Inoue-Yanagimachi, M and Sato, W and Himori, N and Yamamoto, M and Nakazawa, T},
title = {Estrogen, via ESR2 receptor, prevents oxidative stress-induced Müller cell death and stimulates FGF2 production independently of NRF2, attenuating retinal degeneration.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110103},
doi = {10.1016/j.exer.2024.110103},
pmid = {39303841},
issn = {1096-0007},
mesh = {Animals ; *Oxidative Stress/drug effects ; *NF-E2-Related Factor 2/metabolism/genetics ; *Ependymoglial Cells/metabolism/drug effects ; Mice ; *Mice, Knockout ; *Fibroblast Growth Factor 2/metabolism ; *Retinal Degeneration/metabolism/prevention &amp; control/pathology ; *Blotting, Western ; *Mice, Inbred C57BL ; Estrogen Receptor beta/metabolism/genetics ; Cell Survival ; Cells, Cultured ; Cell Death ; Enzyme-Linked Immunosorbent Assay ; Hydrogen Peroxide/toxicity ; Estrogens/pharmacology ; Disease Models, Animal ; },
abstract = {In this study, we aimed to investigate the effects of the deficient antioxidative gene, nuclear factor-erythroid 2-related factor 2 (Nrf2), on 17β-estradiol (E2)-mediated oxidative stress response, with a specific focus on growth factor production and cell death in Müller cells and retinal tissue. Administration of hydrogen peroxide (H2O2) reduced the viability of Müller cells derived from Nrf2 wild-type (WT) and knockout (KO) mice. However, this effect was more significant in the KO cells than in the WT cells. Pretreatment with E2 inhibited H2O2-induced cell death in both Nrf2 WT and KO Müller cell genotypes. Small interfering RNA-mediated gene silencing of estrogen receptor 2 (Esr2) attenuated the cell survival-promoting activity of E2 in Nrf2 KO Müller cells, while other identified estrogen receptors, Esr1 or G protein-coupled estrogen receptor 1 (Gper1), had no effect. Western blotting revealed higher ESR2 expression levels in Nrf2 KO cells than in WT Müller cells. Conditioned media from E2-and H2O2-treated Nrf2 WT or KO Müller cells enhanced the dissociated retinal cell viability compared with H2O2-treated cells. Both quantitative reverse-transcription polymerase chain reaction assay (qRT-PCR) and enzyme-linked immunosorbent assay exhibited a significant increase in fibroblast growth factor 2 (FGF2) expression levels in E2-and H2O2-treated Nrf2 WT and KO Müller cells compared to those in E2-treated cells. In vivo, administration of N-methyl-N-nitrosourea (MNU) reduced the thickness and cell density of the outer nuclear layer (ONL) in Nrf2 KO mice and enhanced the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the ONL. However, E2 administration attenuated these defects in MNU-treated mice. Concomitant administration of MNU and E2 enhanced FGF2 protein levels in retinal lysates of Nrf2 KO mice. In conclusion, E2 demonstrated a significant role in preventing oxidative stress-induced retinal cell death by stimulating FGF2 production in Müller cells, independent of the Nrf2 gene. Based on these findings, we anticipate that exogenous administration of estrogens or ESR2-selective agonists could aid in treating patients with oxidative stress-related retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa.},
}
@article {pmid39303543,
year = {2024},
author = {Li, M and Xu, Q and Fan, Q and Li, H and Zhang, Y and Jiang, F and Qu, Y},
title = {Small molecule SIRT1 activators counteract oxidative stress-induced inflammasome activation and nucleolar stress in retinal degeneration.},
journal = {International immunopharmacology},
volume = {142},
number = {Pt B},
pages = {113167},
doi = {10.1016/j.intimp.2024.113167},
pmid = {39303543},
issn = {1878-1705},
mesh = {Animals ; *Oxidative Stress/drug effects ; *Inflammasomes/metabolism ; *Sirtuin 1/metabolism/genetics ; *Iodates ; Humans ; *Retinal Degeneration/drug therapy/pathology/metabolism ; *Mice, Inbred C57BL ; Cell Line ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Mice ; Hydrogen Peroxide/metabolism ; Resveratrol/pharmacology/therapeutic use ; Disease Models, Animal ; Male ; Reactive Oxygen Species/metabolism ; Heterocyclic Compounds, 2-Ring ; },
abstract = {BACKGROUND: The nicotinamide adenosine dinucleotide-dependent deacetylase Sirtuin 1 (SIRT1) has been identified as a protective factor that inhibits the activation of nucleotide-binding and oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. However, whether pharmacological SIRT1 activators can protect retinal pigment epithelial (RPE) cells against oxidative and inflammatory injuries related to age-related macular degeneration remains to be explored.<br><br>METHODS: Two small molecule specific SIRT1 activators (SRT2104 and CAY10602) were tested, with resveratrol being used as a positive control. Mouse models with sodium iodate-induced retinal degeneration were constructed. ARPE-19 cells in culture were used for in vitro experiments. The effects of SIRT1 activators on H2O2-induced ARPE-19 cell injury were determined by reactive oxygen species quantification, western blotting, flow cytometry and immunofluorescence staining. In vivo, the severity of retinal damage was assessed using flash electroretinography and histopathological analysis.<br><br>RESULTS: In vitro, SRT2104, CAY10602 and resveratrol significantly attenuated H2O2-induced cell death, nucleolar stress response, and reactive oxygen species accumulation. In H2O2-stimulated cells, SIRT1 activators reduced the level of NLRP3, inhibited the activation of caspase-1, and decreased the production of interleukin (IL)-1&#x3b2; and IL-18. The inhibitory effects of SIRT1 activators on caspase-1 activation and IL-1&#x3b2; production were blunted by SIRT1 gene silencing. In vivo, treatment with SRT2104 or CAY10602 in mice with sodium iodate-induced retinal degeneration markedly improved the retinal functions and reduced the loss of RPE cells.<br><br>CONCLUSION: Our study suggests that small molecule SIRT1 activators are effective for protection of RPE cells against oxidative stress-induced NLRP3 inflammasome activation, highlighting potential applications in the treatment of macular degeneration associated RPE dysfunctions.},
}
@article {pmid39297887,
year = {2025},
author = {Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Fakhretdinova, AA and Gilmanshin, TR and Panda-Jonas, S and Jonas, JB},
title = {Prevalence of age-related macular degeneration and retinal pseudodrusen in an elderly population. The ural very old study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {2},
pages = {291-304},
pmid = {39297887},
issn = {1435-702X},
mesh = {Humans ; Female ; Male ; Prevalence ; Aged, 80 and over ; *Retinal Drusen/epidemiology/diagnosis ; Tomography, Optical Coherence/methods ; *Macular Degeneration/epidemiology/diagnosis ; Fundus Oculi ; *Population Surveillance/methods ; Age Distribution ; Cross-Sectional Studies ; Fluorescein Angiography ; },
abstract = {PURPOSE: To assess the prevalence of age-related macular degeneration (AMD) and reticular pseudodrusen (RPD) in very old individuals.<br><br>METHODS: The population-based Ural Very Old Study consisted of 1526 (81.1%) out of 1882 eligible individuals aged 85&#x2009;+&#x2009;years. All individuals living in the study regions and having an age of 85&#x2009;+&#x2009;years were eligible for the study. The presence of AMD and RPDs was assessed on color fundus photographs, red-free fundus images, and optical coherence tomographic images.<br><br>RESULTS: The study included 932 (61.1% of 1526) individuals (age:88.6&#x2009;&#xb1;&#x2009;2.7 years) with available fundus images. Prevalence of any, early, intermediate and late AMD was 439/932 (47.1%; 95%CI:44.0,50.0), 126/932 (13.5%; 95% CI:11.0,16.0), 185/932 (19.8%; 95% CI:17.3,22.3) and 128/932 (13.7%; 95% CI:11.7,15.7), respectively. Neovascular AMD was present in 63 eyes (6.8%;95%CI:5.3,8.3) and geographic atrophy in 65 eyes (7.0%;95%CI:5.0,9.0). Higher prevalence of any AMD and late AMD was significantly correlated with urban region of habitation (OR:3.34; 95% CI:2.37,4.71;&#xa0;P&#x2009;<&#x2009;0.001), and with older age (OR:1.12; 95% CI:1.04,1.19;&#xa0;P&#x2009;=&#x2009;0.001), female sex (OR:1.63; 95%CI:1.02,2.60;&#xa0;P&#x2009;=&#x2009;0.04), and urban region of habitation (OR:2.89; 95% CI:1.59,5.26;&#xa0;P&#x2009;<&#x2009;0.001), respectively. RPDs (assessed in 889 (58.3%) study participants) were present in 220/889 participants (24.7%; 95%CI:21.7,27.7). Higher RPD prevalence was associated (multivariable analysis) with higher serum concentration of the rheumatoid factor (OR:1.15; 95% CI:1.04,1.28;&#xa0;P&#x2009;=&#x2009;0.008), shorter axial length (OR:0.84;95%CI:0.71,0.00;P&#x2009;=&#x2009;0.04), and higher degree of nuclear cataract (OR:1.06; 95% CI:1.01,1.12;&#xa0;P&#x2009;=&#x2009;0.02). AMD was the main cause for vision impairment in 230 (24.7%) participants, for moderate-to-severe vision impairment in 75 (8.0%; 95% CI: 6.4, 10.0) individuals, and for blindness in 15 (1.6%; 95%CI: 0.8, 2.5) persons respectively.<br><br>CONCLUSIONS: In this ethnically mixed, very old population, AMD prevalence (any AMD:47.1%;late AMD:13.7%) was statistically independent of most systemic and ocular parameters. Higher RPD prevalence correlated with shorter axial length.<br><br>KEY MESSAGES: What is known The prevalence of age-related macular degeneration (AMD) has been explored in many studies and societies. Information is missing about its prevalence and associations in very old individuals. The same holds true for reticular pseudodrusen of the macula. What is new In an ethnically mixed, very old population in Bashkortostan / Russia, the prevalence of AMD (any AMD: 47.1%; late AMD:13.7%) was statistically independent of most systemic and ocular parameters. Higher prevalence of reticular pseudodrusen correlated with shorter axial length.},
}
@article {pmid39302753,
year = {2024},
author = {James, LM},
title = {Age-related macular degeneration.},
journal = {Nursing},
volume = {54},
number = {10},
pages = {50-53},
doi = {10.1097/NSG.0000000000000079},
pmid = {39302753},
issn = {1538-8689},
mesh = {Aged ; Humans ; Middle Aged ; *Macular Degeneration/nursing/diagnosis/epidemiology/physiopathology ; Nursing Diagnosis ; Risk Factors ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of visual impairment in patients age 50 and older, with an estimated 200 million people affected worldwide and a projected 288 million by 2040. This article provides an overview of the epidemiology, risk factors, pathophysiology, clinical manifestations, diagnosis, management, and nursing considerations for AMD to equip nurses with the knowledge to play a crucial role in the early detection of this disease.},
}
@article {pmid39302645,
year = {2024},
author = {Tsuboi, K and You, QS and Wang, J and Guo, Y and Flaxel, CJ and Hwang, TS and Huang, D and Jia, Y and Bailey, ST},
title = {Quantitative Evaluation of Type 1 and Type 2 Choroidal Neovascularization Components Under Treatment With Projection-Resolved OCT Angiography.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {11},
pages = {32},
pmid = {39302645},
issn = {1552-5783},
support = {P30 EY010572/EY/NEI NIH HHS/United States ; R01 EY024544/EY/NEI NIH HHS/United States ; R01 EY027833/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; *Fluorescein Angiography/methods ; *Angiogenesis Inhibitors/therapeutic use ; *Intravitreal Injections ; Aged ; *Choroidal Neovascularization/drug therapy/diagnostic imaging/diagnosis ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Visual Acuity ; Ranibizumab/therapeutic use/administration &amp; dosage ; Wet Macular Degeneration/drug therapy/diagnosis ; Fundus Oculi ; Follow-Up Studies ; Undertreatment ; },
abstract = {PURPOSE: To evaluate the response of type 1 and type 2 macular neovascularization (MNV) components under anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration (AMD) using projection-resolved optical coherence tomography angiography (PR-OCTA).<br><br>METHODS: This retrospective study included eyes with treatment-na&#xef;ve exudative AMD treated with anti-VEGF injections under a pro re nata (PRN) protocol over 1 year. Two-dimensional MNV areas and three-dimensional MNV volumes were derived from macular PR-OCTA scans using an automated convolutional neural network. MNV was detected as flow signal within the outer retinal slab. Type 1 components and type 2 components were analyzed separately.<br><br>RESULTS: Of 17 enrolled eyes, 12 eyes were pure type 1 MNV and five eyes were type 2 MNV. In eyes with pure type 1, the total (sum of type 1 and type 2 components) MNV area and volume did not change from baseline to 6 months or 12 months (P > 0.05). In eyes with type 2 MNV, the total MNV area significantly decreased from the baseline to 6 months (P = 0.0074) and 12 months (P = 0.014). The total type 2 MNV volume also decreased from baseline visit to visits at 6 months and at 12 months, nearing statistical signifiicance (P = 0.061 and P = 0.074). In eyes with type 2 MNV, the type 1 component increased from 0.093 mm2 to 0.30 mm2 (P = 0.058), and the type 2 component decreased from 0.37 mm2 at 6 months to 0 at 12 months (P = 0.0087).<br><br>CONCLUSIONS: Type 1 and type 2 MNV may have different response under PRN anti-VEGF treatment over 1 year.},
}
@article {pmid39302424,
year = {2024},
author = {Hu, J and Yao, Y and Ge, T and Wang, S and Liu, S and Zhu, Q and Song, X and Jia, R and Zhuang, A},
title = {Ultra-processed foods consumption and risk of age-related eye diseases: a prospective cohort study with UK biobank.},
journal = {European journal of nutrition},
volume = {63},
number = {8},
pages = {3175-3186},
pmid = {39302424},
issn = {1436-6215},
support = {20DZ2270800//Science and Technology Commission of Shanghai Municipality/ ; 23ZR1438400//Science and Technology Commission of Shanghai Municipality/ ; SHSMU-ZDCX20210900//Innovative Research Team of High-level Local University in Shanghai/ ; SHSMU-ZDCX20210902//Innovative Research Team of High-level Local University in Shanghai/ ; },
mesh = {Humans ; Male ; United Kingdom/epidemiology ; Female ; Middle Aged ; Prospective Studies ; Aged ; Risk Factors ; *Biological Specimen Banks/statistics &amp; numerical data ; *Macular Degeneration/epidemiology/etiology ; *Fast Foods/statistics &amp; numerical data/adverse effects ; *Diet/statistics &amp; numerical data/methods/adverse effects ; *Cataract/epidemiology/etiology ; Cohort Studies ; Eye Diseases/epidemiology/etiology ; Glaucoma/epidemiology ; Proportional Hazards Models ; Food Handling/methods ; Follow-Up Studies ; Food, Processed ; UK Biobank ; },
abstract = {PURPOSE: Consumption of ultra-processed foods (UPF) has been associated with increased risks of various age-related diseases. However, the potential association between UPF consumption and age-related eye diseases (AREDs) remains unclear. We aim to assess the associations between consumption of UPF and risk of AREDs including age-related macular degeneration (AMD), cataract and glaucoma.<br><br>METHODS: We included 156,232 individuals aged 50 or older, who were free from AREDs from UK biobank study. Dietary intake data were collected using 24-h dietary assessments. UPF is defined according to the NOVA classification, and all participants are divided into four quartiles based on the weight proportion (%) of UPF. During a median of 10&#xa0;years of follow-up. Cox proportional hazards were used to estimate the association between the proportion of UPF in the diet and the subsequent risk of various AREDs.<br><br>RESULTS: After adjusting for multiple variables, individuals in the highest quartiles for UPF consumption exhibited an increased risk of AMD (hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.01-1.63; p&#x2009;=&#x2009;0.03), cataract (HR: 1.10; 95% CI: 1.01-1.20; p&#x2009;=&#x2009;0.04), and glaucoma (HR: 1.27; 95% CI: 0.98-1.63; p&#x2009;=&#x2009;0.06) compared to those in the lowest quartiles. Moreover, a 10% increase in the weight of UPF in diet was associated with an 8% higher risk of AMD (HR: 1.08; 95% CI: 1.01-1.15; p&#x2009;=&#x2009;0.03), a 3% higher risk of cataract (HR: 1.03; 95% CI: 1.00-1.06; p&#x2009;=&#x2009;0.04), and a 7% higher risk of glaucoma (HR: 1.07; 95% CI: 1.00-1.15; p&#x2009;=&#x2009;0.05).<br><br>CONCLUSION: Our results suggest that a higher proportion of UPF in the diet was significantly link with an elevated risk of AMD and cataract. While additional research is necessary to validate these findings in diverse populations and settings, these results offer initial evidence to endorse public health initiatives that encourage limiting consumption of UPF.},
}
@article {pmid39300187,
year = {2025},
author = {Barai, I and Mathew, RG and Sivaprasad, S and Henein, C},
title = {Infographic: Efficacy and safety of intravitreal aflibercept treat-and-extend regimens in exudative age-related macular degeneration: ALTAIR study.},
journal = {Eye (London, England)},
volume = {39},
number = {Suppl 1},
pages = {120-122},
doi = {10.1038/s41433-024-03336-2},
pmid = {39300187},
issn = {1476-5454},
}
@article {pmid39299944,
year = {2024},
author = {Sozen-Delil, FI and Comba, OB and Ucar, G},
title = {Evaluation of insomnia effect on ganglion cell complex, middle retina, and choroid.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {381},
pmid = {39299944},
issn = {1573-2630},
mesh = {Humans ; Female ; Male ; *Tomography, Optical Coherence/methods ; *Retinal Ganglion Cells/pathology ; *Choroid/pathology/diagnostic imaging ; *Sleep Initiation and Maintenance Disorders/diagnosis ; Middle Aged ; Adult ; *Nerve Fibers/pathology ; Retina/pathology/diagnostic imaging ; },
abstract = {PURPOSE: Insomnia is a common psychiatric disorder that has oxidative and degenerative effects on the brain. It is thought that the brain's processes affect the retina through their synaptic connections. However, the effects of sleep disorders on the retina and choroid are not fully understood. We aimed to investigate the impact of insomnia on retinal nerve fiber layer (RNFL), central foveal thickness, retinal layers, and choroidal thickness.<br><br>METHODS: The right eye of 16 healthy controls and 15 patients with insomnia complaints for 3&#xa0;months, no history of psychiatric drug use, and an Insomnia Severity Index (ISI) score of 15 or higher were included in the study. The retinal layers and RNFL analyses were performed using optical coherence tomography (OCT), and choroidal layers were analyzed using enhanced depth imaging OCT.<br><br>RESULTS: Nasal and temporal ganglion cell complex thicknesses were significantly lower in patients with insomnia compared to the controls (97&#xa0;&#x3bc;m vs. 111&#xa0;&#x3bc;m P&#x2009;=&#x2009;0.004; 94&#xa0;&#x3bc;m vs. 105&#xa0;&#x3bc;m P&#x2009;=&#x2009;0.012, respectively). A significant negative correlation was detected between the ISI score and global RNFL thickness (rho, P&#x2009;=&#x2009;0.03) Additionally, pachychoroid-like vascular structures were observed in choroidal images.<br><br>CONCLUSION: These changes in the retina and the choroid layers due to insomnia may be precursors to retinal degenerative conditions, such as age-related macular degeneration that may occur in the future. Multicenter studies including more patients are needed to demonstrate the importance of quality sleep for eye health.},
}
@article {pmid39296908,
year = {2024},
author = {Li, K and Liu, J and Li, X and Liu, X and Hu, P and He, M},
title = {Association of EPA and DHA with age-related macular degeneration: a cross-sectional study from NHANES.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1440479},
pmid = {39296908},
issn = {2296-858X},
abstract = {PURPOSE: This cross-sectional study conducted in the general US population investigated the association between dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the prevalence of AMD.<br><br>METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were utilized, including 4,842 participants aged 40 years and older. Dietary EPA and DHA intake data were collected through two 24-h dietary recall interviews and adjusted for weight. AMD was determined by a standardized grading system based on the presence of key features of AMD in color photographs of the macula. Multivariate logistic regression and restricted cubic spline models evaluated the associations between dietary EPA and DHA intake and AMD. Subgroup analysis and interaction analysis explored the influence of covariates.<br><br>RESULTS: A total of 4,842 participants were included. In the multivariate-adjusted model 2, the odds ratios (ORs) with 95% confidence intervals (CIs) for AMD were 0.86 (0.75, 0.99) and 0.88 (0.80, 0.97) per unit increase in dietary EPA and DHA intake, respectively. Interaction testing revealed significant effect modification by age, education, and BMI on the EPA-AMD association, indicating these factors significantly impacted this inverse relationship (p-interaction < 0.05). Similarly, age, education, BMI, and cataract surgery history modified the inverse DHA-AMD association (p-interaction < 0.05). Dose-response analyses demonstrated a negative correlation between dietary EPA and DHA intake with AMD prevalence (p-nonlinearity = 0.184 and 0.548, respectively).<br><br>CONCLUSION: Our findings suggested that higher dietary EPA and DHA intake could be associated with lower AMD risk in older US adults. Age, education level, BMI, and history of cataract surgery may influence this inverse association.},
}
@article {pmid39296899,
year = {2024},
author = {Prieto-López, L and Pereiro, X and Vecino, E},
title = {The mechanics of the retina: Müller glia role on retinal extracellular matrix and modelling.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1393057},
pmid = {39296899},
issn = {2296-858X},
abstract = {The retina is a highly heterogeneous tissue, both cell-wise but also regarding its extracellular matrix (ECM). The stiffness of the ECM is pivotal in retinal development and maturation and has also been associated with the onset and/or progression of numerous retinal pathologies, such as glaucoma, proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), epiretinal membrane (ERM) formation or uveitis. Nonetheless, much remains unknown about the biomechanical milieu of the retina, and specifically the role that Müller glia play as principal mechanosensors and major producers of ECM constituents. So far, new approaches need to be developed to further the knowledge in the field of retinal mechanobiology for ECM-target applications to arise. In this review, we focus on the involvement of Müller glia in shaping and altering the retinal ECM under both physiological and pathological conditions and look into various biomaterial options to more accurately replicate the impact of matrix stiffness in vitro.},
}
@article {pmid39296574,
year = {2024},
author = {Huang, HY and Wang, J and Qin, B and Tan, Y},
title = {Investigating the causal link between gut microbiota and dry age-related macular degeneration: a bidirectional Mendelian randomization study.},
journal = {International journal of ophthalmology},
volume = {17},
number = {9},
pages = {1723-1730},
pmid = {39296574},
issn = {2222-3959},
abstract = {AIM: To assess the causal link between 211 gut microbiota (GM) taxa and dry age-related macular degeneration (dAMD) risk.<br><br>METHODS: Mendelian randomization using instrumental factors taken from a genome-wide association study (GWAS) were used. Inverse variance weighted (IVW) analysis and sensitivity analysis were performed on the FinnGen project, which included 5095 cases and 222 590 controls.<br><br>RESULTS: The IVW analysis showed substantial genus- and family-level relationships between GM taxa and dAMD risk. Specifically, the family Peptococcaceae (P=0.03), genus Bilophila (P=3.91&#xd7;10[-3]), genus Faecalibacterium (P=6.55&#xd7;10[-3]), and genus Roseburia (P=0.04) were linked to a higher risk of developing dAMD, while the genus Candidatus Soleaferrea (P=7.75&#xd7;10[-4]), genus Desulfovibrio (P=0.04) and genus Eubacterium ventriosum group (P=0.04) exhibited a protective effect against dAMD. No significant causal relationships were observed at higher taxonomic levels. Additionally, in the reverse IVW analysis, no meaningful causal effects of the 7 GM taxa.<br><br>CONCLUSION: These findings give support for the gut-retina axis participation in dAMD and shed light on putative underlying processes. Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.},
}
@article {pmid39296552,
year = {2024},
author = {Wu, JL and Zhang, M and Sun, XD},
title = {Beta-alanine promotes angiogenesis in laser-induced choroidal neovascularization mice models.},
journal = {International journal of ophthalmology},
volume = {17},
number = {9},
pages = {1592-1598},
pmid = {39296552},
issn = {2222-3959},
abstract = {AIM: To investigate the effect of β-alanine (BA) on laser-induced choroidal neovascularization (CNV) mice models.<br><br>METHODS: Laser-induced CNV mice models were established, and BA was administrated for one week and two weeks in advance, separately. Furthermore, retinal pigment epithelium (RPE)-choroid flat mounts were separated, and immunohistochemical staining was performed. The laser-induced CNV lesion areas were measured and compared. In addition, liver and kidney morphologies were observed to identify potential hepatorenal toxicity.<br><br>RESULTS: Enlarged CNV lesion areas were observed in the BA treated group. No significant differences were observed in the liver and kidney sections between groups.<br><br>CONCLUSION: BA treatment increase CNV lesion areas, suggesting the detrimental effects of BA as a nutritional supplement in age-related macular degeneration (AMD) population.},
}
@article {pmid39296359,
year = {2024},
author = {Sun, Q and Ni, Y and Wang, K and Zhang, H and Liu, J and Xu, L and Zhao, Y},
title = {Rhodium nanozyme mitigates RPE degeneration and preserves vision in age-related macular degeneration via antioxidant and anti-inflammatory mechanisms.},
journal = {Materials today. Bio},
volume = {28},
number = {},
pages = {101230},
pmid = {39296359},
issn = {2590-0064},
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people worldwide. However, there are currently no effective treatments for AMD. Oxidative stress-induced retinal pigment epithelium (RPE) degeneration and the inflammatory response are the main causes of AMD. In this study, a polyethylene glycol (PEG)-coated rhodium nanozyme (PEG-RhZ) with excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) elimination capability was synthesized for the treatment of AMD. PEG-RhZs protected RPE cell viability and barrier function upon exposure to oxidative stress stimuli. Additionally, microglial migration and iNOS, IL-1β and TNF-α expression were inhibited by PEG-RhZs. In the acute phase of the AMD model, PEG-RhZs significantly alleviated RPE oxidative damage and inhibited microglial activation. In the late stage of the AMD model, PEG-RhZs reduced photoreceptor loss and improved vision impairment. Furthermore, PEG-RhZs showed good biocompatibility and stability both in vitro and in vivo. Collectively, our findings suggest the therapeutic potential of PEG-RhZs for AMD treatment. STATEMENT OF SIGNIFICANCE: AMD is a kind of retinal degenerative disease that poses heavy health burden globally. PEG-RhZs exhibiting robust ROS and RNS scavenging capabilities have shown promise in safeguarding retinal pigment epithelium (RPE) from oxidative stress, suppressing microglia activation and the secretion of pro-inflammatory molecules, mitigating loss of retinal photoreceptor cells, and ameliorating visual impairment. The commendable antioxidant properties, biological safety, and biostability of PEG-RhZs offer valuable insights for the clinical management of AMD.},
}
@article {pmid39294233,
year = {2024},
author = {Sim, SS and Cheong, KX and Chan, HH and Choo, JQH and Tsai, ASH and Lee, SY and Yeo, IYS and Cheung, CMG and Teo, KYC},
title = {Pneumatic displacement of submacular haemorrhage secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {Eye (London, England)},
volume = {38},
number = {17},
pages = {3374-3381},
pmid = {39294233},
issn = {1476-5454},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity/physiology ; *Retinal Hemorrhage/etiology/therapy/diagnosis/physiopathology ; Aged ; *Angiogenesis Inhibitors/therapeutic use ; *Intravitreal Injections ; Aged, 80 and over ; *Wet Macular Degeneration/complications/drug therapy/physiopathology/diagnosis ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/therapeutic use/administration &amp; dosage ; *Tomography, Optical Coherence ; Fluorescein Angiography ; Endotamponade ; Bevacizumab/therapeutic use ; Polyps/complications/diagnosis/physiopathology ; Choroidal Neovascularization/drug therapy/physiopathology/etiology/therapy ; Combined Modality Therapy ; Choroid Diseases/complications/diagnosis/physiopathology ; Fluorocarbons/administration &amp; dosage ; Choroid/blood supply ; Polypoidal Choroidal Vasculopathy ; },
abstract = {BACKGROUND: To compare the visual and anatomical outcomes of pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (VEGF) therapy versus anti-VEGF monotherapy in treatment-naive eyes with submacular haemorrhage (SMH) secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.<br><br>METHODS: In a retrospective comparative interventional study of 57 eyes, the changes in logMAR visual acuity (VA), and SMH height and area at baseline at months 1, 3 and 12 were compared between the PD and non-PD groups.<br><br>RESULTS: There was no significant difference in mean VA in the PD versus non-PD group at month 12 (1.1 versus 0.7, p&#x2009;=&#x2009;0.09). At baseline, the PD group, compared to the non-PD group, had significantly larger SMH area (35.9 versus 26.9&#x2009;mm[2], p&#x2009;=&#x2009;0.04) and SMH height at the fovea (733.7 versus 503.6&#x2009;&#xb5;m, p&#x2009;<&#x2009;0.01). The greatest reduction in SMH height and area occurred between baseline and month 1 in the PD group, which was faster than between month 1 and month 3 in the non-PD group, with similar findings in the matched pair analysis matched for SMH height and area. In the multivariable analysis, only baseline VA was associated with VA outcomes (month 1: &#x3b2;&#x2009;=&#x2009;-0.46, 95% [confidence interval] CI&#x2009;=&#x2009;-0.78 to -0.14, p&#x2009;=&#x2009;0.006; month 3: &#x3b2;&#x2009;=&#x2009;-0.52, 95% CI&#x2009;=&#x2009;-0.86 to -0.18, p&#x2009;=&#x2009;0.004; and month 12: &#x3b2;&#x2009;=&#x2009;-0.78, 95% CI&#x2009;=&#x2009;-1.16 to -0.39, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: The visual outcome of SMH at month 12 in nAMD and PCV is poor regardless of whether PD is performed in addition to anti-VEGF therapy, although a more rapid resolution of SMH can be expected.},
}
@article {pmid39294229,
year = {2025},
author = {Barai, I and Sivaprasad, S and Henein, C},
title = {Infographic: ranibizumab or bevacizumab treat &amp; extend for neovascular age-related macular degeneration (AMD): LUCAS trial.},
journal = {Eye (London, England)},
volume = {39},
number = {Suppl 1},
pages = {129-131},
pmid = {39294229},
issn = {1476-5454},
}
@article {pmid39294227,
year = {2025},
author = {Barai, I and Sivaprasad, S and Henein, C},
title = {Infographic: The port delivery system with ranibizumab for neovascular age-related macular degeneration: LADDER trial.},
journal = {Eye (London, England)},
volume = {39},
number = {Suppl 1},
pages = {126-128},
doi = {10.1038/s41433-024-03337-1},
pmid = {39294227},
issn = {1476-5454},
}
@article {pmid39294152,
year = {2024},
author = {Hu, Y and Gao, Y and Gao, W and Luo, W and Yang, Z and Xiong, F and Chen, Z and Lin, Y and Xia, X and Yin, X and Deng, Y and Ma, L and Li, G},
title = {AMD-SD: An Optical Coherence Tomography Image Dataset for wet AMD Lesions Segmentation.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1014},
pmid = {39294152},
issn = {2052-4463},
mesh = {*Tomography, Optical Coherence ; Humans ; *Algorithms ; *Wet Macular Degeneration/diagnostic imaging ; Retina/diagnostic imaging/pathology ; },
abstract = {Wet Age-related Macular Degeneration (wet AMD) is a common ophthalmic disease that significantly impacts patients' vision. Optical coherence tomography (OCT) examination has been widely utilized for diagnosing, treating, and monitoring wet AMD due to its cost-effectiveness, non-invasiveness, and repeatability, positioning it as the most valuable tool for diagnosis and tracking. OCT can provide clear visualization of retinal layers and precise segmentation of lesion areas, facilitating the identification and quantitative analysis of abnormalities. However, the lack of high-quality datasets for assessing wet AMD has impeded the advancement of related algorithms. To address this issue, we have curated a comprehensive wet AMD OCT Segmentation Dataset (AMD-SD), comprising 3049 B-scan images from 138 patients, each annotated with five segmentation labels: subretinal fluid, intraretinal fluid, ellipsoid zone continuity, subretinal hyperreflective material, and pigment epithelial detachment. This dataset presents a valuable opportunity to investigate the accuracy and reliability of various segmentation algorithms for wet AMD, offering essential data support for developing AI-assisted clinical applications targeting wet AMD.},
}
@article {pmid39292553,
year = {2024},
author = {Lad, EM and Fleckenstein, M and Holz, FG and Shen, L and Priore, LVD and Silva, R and Staurenghi, G and Waheed, N and Chakravarthy, U},
title = {Informing Endpoints for Clinical Trials of Geographic Atrophy.},
journal = {Annual review of vision science},
volume = {10},
number = {1},
pages = {455-476},
doi = {10.1146/annurev-vision-101922-045110},
pmid = {39292553},
issn = {2374-4650},
mesh = {Humans ; *Geographic Atrophy/drug therapy/physiopathology ; *Clinical Trials as Topic ; Visual Acuity/physiology ; Disease Progression ; Endpoint Determination ; },
abstract = {Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion. In addition, we review the relationship between GA growth and the various measures of vision that reflect changes in function. We consider the reasons for the discordance between the anatomical and functional endpoints in current use and discuss methods to align these key outcomes.},
}
@article {pmid39290166,
year = {2025},
author = {Lavery, TCM and Rasmussen, CA and Katz, AW and Kim, CBY and Ver Hoeve, JN and Miller, PE and Sonnentag, PJ and Christian, BJ and Murphy, CJ and Piwnica-Worms, DR and Gammon, ST and Qiu, X and Kaufman, PL and Nork, TM},
title = {Development of Microcystoid Macular Degeneration in the Retina of Nonhuman Primates: Time-Course and Associated Pathologies.},
journal = {Current eye research},
volume = {50},
number = {1},
pages = {93-100},
pmid = {39290166},
issn = {1460-2202},
support = {P51 RR000167/RR/NCRR NIH HHS/United States ; P30 EY016665/EY/NEI NIH HHS/United States ; P51 OD011106/OD/NIH HHS/United States ; R01 CA273130/CA/NCI NIH HHS/United States ; S10 OD026957/OD/NIH HHS/United States ; R01 EY019587/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Macaca fascicularis ; *Tomography, Optical Coherence/methods ; *Macaca mulatta ; *Retinal Ganglion Cells/pathology ; *Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/pathology ; *Disease Models, Animal ; Ophthalmoscopy ; Glaucoma/diagnosis ; Axotomy ; Time Factors ; Optic Atrophy/diagnosis/pathology ; Retina/pathology ; Vacuoles/pathology ; Male ; },
abstract = {PURPOSE: Microcystoid macular degeneration (MMD) is a condition where cystoid vacuoles develop within the inner nuclear layer of the retina in humans in a variety of disorders. Here we report the occurrence of MMD in non-human primates (NHPs) with various retinal ganglion cell (RGC) pathologies and evaluate the hypothesis that MMD does not precede RGC loss but follows it.<br><br>METHODS: Morphological studies were performed of the retinas of NHPs, specifically both rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), in which MMD was identified after induction of experimental glaucoma (EG), hemiretinal endodiathermy axotomy (HEA), and spontaneous idiopathic bilateral optic atrophy. In vivo imaging analyses included fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT), adaptive optics scanning laser ophthalmoscopy (AOSLO), light microscopy, and electron microscopy.<br><br>RESULTS: MMD, like that seen on OCT scans of humans, was found in both rhesus and cynomolgus macaques with EG. Of 13 cynomolgus macaques with chronic EG imaged once with OCT six of 13 animals were noted to have MMD. MMD was also evident in a cynomolgus macaque with bilateral optic atrophy. Following HEA, MMD did not develop until at least 2&#x2009;weeks following the RNFL loss.<br><br>CONCLUSION: These data suggest that MMD may be caused by a retrograde trans-synaptic process related to RGC loss. MMD is not associated with inflammation, nor would it be an independent indicator of drug toxicity per se in pre-clinical regulatory studies. Because of its inconsistent appearance and late development, MMD has limited use as a clinical biomarker.},
}
@article {pmid39289517,
year = {2025},
author = {Vujosevic, S and Limoli, C and Kozak, I},
title = {Hallmarks of aging in age-related macular degeneration and age-related neurological disorders: novel insights into common mechanisms and clinical relevance.},
journal = {Eye (London, England)},
volume = {39},
number = {5},
pages = {845-859},
pmid = {39289517},
issn = {1476-5454},
mesh = {Humans ; *Macular Degeneration/physiopathology/metabolism ; *Aging/physiology ; *Neurodegenerative Diseases/physiopathology ; *Nervous System Diseases/physiopathology ; Clinical Relevance ; },
abstract = {Age-related macular degeneration (AMD) and age-related neurological diseases (ANDs), such as Alzheimer's and Parkinson's Diseases, are increasingly prevalent conditions that significantly contribute to global morbidity, disability, and mortality. The retina, as an accessible part of the central nervous system (CNS), provides a unique window to study brain aging and neurodegeneration. By examining the associations between AMD and ANDs, this review aims to highlight novel insights into fundamental mechanisms of aging and their role in neurodegenerative disease progression. This review integrates knowledge from the emerging field of aging research, which identifies common denominators of biological aging, specifically loss of proteostasis, impaired macroautophagy, mitochondrial dysfunction, and inflammation. Finally, we emphasize the clinical relevance of these pathways and the potential for cross-disease therapies that target common aging hallmarks. Identifying these shared pathways could open avenues to develop therapeutic strategies targeting mechanisms common to multiple degenerative diseases, potentially attenuating disease progression and promoting the healthspan.},
}
@article {pmid39287535,
year = {2024},
author = {Ghalibafan, S and Taylor Gonzalez, DJ and Cai, LZ and Graham Chou, B and Panneerselvam, S and Conrad Barrett, S and Djulbegovic, MB and Yannuzzi, NA},
title = {APPLICATIONS OF MULTIMODAL GENERATIVE ARTIFICIAL INTELLIGENCE IN A REAL-WORLD RETINA CLINIC SETTING.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1732-1740},
pmid = {39287535},
issn = {1539-2864},
support = {//Macula Foundation/ ; },
mesh = {Humans ; Cross-Sectional Studies ; Retrospective Studies ; *Artificial Intelligence ; Female ; Male ; *Retinal Diseases/diagnosis ; Middle Aged ; Aged ; Retina/diagnostic imaging ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: This study evaluates a large language model, Generative Pre-trained Transformer 4 with vision, for diagnosing vitreoretinal diseases in real-world ophthalmology settings.<br><br>METHODS: A retrospective cross-sectional study at Bascom Palmer Eye Clinic, analyzing patient data from January 2010 to March 2023, assesses Generative Pre-trained Transformer 4 with vision's performance on retinal image analysis and International Classification of Diseases 10th revision coding across 2 patient groups: simpler cases (Group A) and complex cases (Group B) requiring more in-depth analysis. Diagnostic accuracy was assessed through open-ended questions and multiple-choice questions independently verified by three retina specialists.<br><br>RESULTS: In 256 eyes from 143 patients, Generative Pre-trained Transformer 4-V demonstrated a 13.7% accuracy for open-ended questions and 31.3% for multiple-choice questions, with International Classification of Diseases 10th revision code accuracies at 5.5% and 31.3%, respectively. Accurately diagnosed posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment. International Classification of Diseases 10th revision coding was most accurate for nonexudative age-related macular degeneration, central retinal vein occlusion, and macular hole in OEQs, and for posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment in multiple-choice questions. No significant difference in diagnostic or coding accuracy was found in Groups A and B.<br><br>CONCLUSION: Generative Pre-trained Transformer 4 with vision has potential in clinical care and record keeping, particularly with standardized questions. Its effectiveness in open-ended scenarios is limited, indicating a significant limitation in providing complex medical advice.},
}
@article {pmid39287534,
year = {2024},
author = {Holekamp, NM and de Beus, AM and Clark, WL and Heier, JS},
title = {PROSPECTIVE TRIAL OF HOME OPTICAL COHERENCE TOMOGRAPHY-GUIDED MANAGEMENT OF TREATMENT EXPERIENCED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1714-1731},
pmid = {39287534},
issn = {1539-2864},
support = {//Notal Vision/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Male ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Prospective Studies ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; *Intravitreal Injections ; Aged, 80 and over ; Ranibizumab/administration &amp; dosage/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Fluorescein Angiography/methods ; Bevacizumab/administration &amp; dosage/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: To evaluate the impact of home optical coherence tomography (OCT)-guided patient management on treatment burden and visual outcomes.<br><br>METHODS: An interventional trial was conducted to compare frequency of treatment and visual acuity for the neovascular age-related macular degeneration patients before and during use of home optical coherence tomography over a period of 6 months. Patient adherence to regular scanning was measured by the number of scans performed per week. The characteristics of episodes of fluid recurrence and classification of typical fluid volume trajectories were performed.<br><br>RESULTS: Twenty-seven eyes (21 with diagnosis of neovascular age-related macular degeneration and one converted during the study), of 15 patients were monitored for 6 months, scanning at 6.2 times/week per eye and yielding 4,435 scans of which 91.2% were eligible for artificial intelligence-based fluid volume quantification. Total number of monitoring weeks before and during the study were 1,555 and 509. The mean (SD) number of weeks per injection before and during home OCT management were 8.0 (4.7) and 15.3 (8.5) (P = 0.004), respectively. The mean (SD) visual acuity change before and during home OCT-based management was 3.5 (12.0) letters and 0.0 (9.5) letters (P = 0.45), respectively, showing no significant impact on visual acuity.<br><br>CONCLUSION: For the first time, remote patient monitoring with a home OCT allowed personalized management of neovascular age-related macular degeneration. This study showed significant reduction in treatment burden while maintaining stable visual acuity.},
}
@article {pmid39287533,
year = {2024},
author = {Bordon, AF and Kaiser, PK and Wolf, A and Cen, L and Heyn, J and Urosevic, D and Dodeller, F and Allmannsberger, L and Silva, R},
title = {EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1704-1713},
pmid = {39287533},
issn = {1539-2864},
support = {//Hexal AG (a Sandoz company), Holzkirchen, Germany/ ; },
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects/therapeutic use ; *Visual Acuity ; Double-Blind Method ; Male ; Female ; *Intravitreal Injections ; Prospective Studies ; Aged ; *Biosimilar Pharmaceuticals/adverse effects/therapeutic use/pharmacokinetics ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects/therapeutic use/pharmacokinetics ; Aged, 80 and over ; Treatment Outcome ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Time Factors ; },
abstract = {PURPOSE: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]).<br><br>METHOD: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics.<br><br>RESULTS: Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL.<br><br>CONCLUSION: Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.},
}
@article {pmid39287532,
year = {2024},
author = {Tong, N and Fan, W and Su, L and Ebraheem, A and Uji, A and Marion, K and Sadda, S},
title = {RELATIONSHIP BETWEEN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS AND NUMBER OF INTRAVITREAL RANIBIZUMAB INJECTIONS IN EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE HARBOR STUDY.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1696-1703},
doi = {10.1097/IAE.0000000000004171},
pmid = {39287532},
issn = {1539-2864},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; Biomarkers ; Fluorescein Angiography/methods ; Follow-Up Studies ; *Intravitreal Injections ; Prospective Studies ; *Ranibizumab/administration &amp; dosage ; Subretinal Fluid ; *Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {PURPOSE: To correlate baseline spectral-domain optical coherence tomography characteristics with the number of as-needed intravitreal injections of ranibizumab over a 24-month follow-up period in eyes with neovascular age-related macular degeneration.<br><br>METHODS: Two hundred thirty-six eyes of 236 subjects with neovascular age-related macular degeneration treated with ranibizumab 0.5 mg pro re nata in the HARBOR study were enrolled. Baseline spectral-domain optical coherence tomography images were evaluated by certified reading center graders for specific morphologic features of the macular neovascularization lesion and surrounding retina. Baseline optical coherence tomography features and patient demographics correlated with the number of injections over the next 2 years.<br><br>RESULTS: The mean number of injections in the 0.5 mg pro re nata group was 8.07 (median 8, 3-12) after 12 months and 14.25 (median 14, 3-24) after 24 months of treatment. After multivariate, linear, regression analysis, the only baseline parameter that was independently associated with a higher injection frequency at both 12 and 24 months was a greater baseline subretinal fluid thickness.<br><br>CONCLUSION: A greater subretinal fluid thickness at baseline was associated with a higher frequency of pro re nata injections over 12 and 24 months in eyes treated with ranibizumab for neovascular age-related macular degeneration. These findings may be of value in counseling patients who are about to initiate therapy for macular neovascularization.},
}
@article {pmid39287531,
year = {2024},
author = {Menean, M and Sacconi, R and Tombolini, B and L'abbate, G and Beretta, F and Bandello, F and Querques, G},
title = {RETICULAR PSEUDODRUSEN DISAPPEARANCE AFTER DEVELOPMENT OF MACULAR NEOVASCULARIZATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1688-1695},
doi = {10.1097/IAE.0000000000004173},
pmid = {39287531},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; Female ; *Retinal Drusen/diagnosis ; Male ; Aged ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Retinal Neovascularization/diagnosis/etiology/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Visual Acuity ; Follow-Up Studies ; Choroidal Neovascularization/drug therapy/physiopathology/diagnosis/etiology ; Wet Macular Degeneration/diagnosis/drug therapy ; Fundus Oculi ; },
abstract = {PURPOSE: To explore changes in reticular pseudodrusen (RPD) number and location after the development of macular neovascularization (MNV) in eyes with prior intermediate age-related macular degeneration, focusing on different retinal regions differently affected by MNV.<br><br>METHODS: This retrospective longitudinal study included intermediate age-related macular degeneration eyes with RPD that developed MNV. Reticular pseudodrusen were assessed at baseline when MNV was diagnosed (MNV stage) and after anti-vascular endothelial growth factor treatment. Three regions of interest were considered: MNV area, subretinal fluid (SRF) area, and a marginal area of 1,000 &#xb5;m around SRF (marginal zone). Reticular pseudodrusen counts were compared with age- and sex-matched control eyes with RPD that did not develop MNV.<br><br>RESULTS: Reticular pseudodrusen number exhibited a significant decrease after MNV development in the MNV area (P = 0.048) and in the area with SRF (P = 0.078). A statistically significant decrease was also disclosed in the marginal area around SRF (P = 0.002), associated with larger SRF areas. Control eyes did not show any significant change in the RPD count.<br><br>CONCLUSION: Reticular pseudodrusen reduction after MNV development suggests a complex interplay involving the MNV itself, the presence of SRF, and trophic changes. The results of this study highlight the role of MNV in retinal nutritional balance and provide intriguing results in the RPD life cycle.},
}
@article {pmid39287530,
year = {2024},
author = {Crincoli, E and Catania, F and Labbate, G and Sacconi, R and Ferrara, S and Parravano, M and Costanzo, E and Querques, G},
title = {MICROVASCULAR CHANGES IN TREATMENT-NAÏVE NONEXUDATIVE MACULAR NEOVASCULARIZATION COMPLICATED BY EXUDATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1679-1687},
doi = {10.1097/IAE.0000000000004194},
pmid = {39287530},
issn = {1539-2864},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Retrospective Studies ; *Fluorescein Angiography/methods ; Aged ; *Retinal Vessels/diagnostic imaging/pathology ; *Wet Macular Degeneration/diagnosis/physiopathology/drug therapy ; Follow-Up Studies ; Aged, 80 and over ; Visual Acuity/physiology ; Choroid/blood supply/diagnostic imaging ; Fundus Oculi ; Angiogenesis Inhibitors/therapeutic use ; Microvessels/diagnostic imaging/pathology ; Retinal Neovascularization/diagnosis/etiology/physiopathology ; Exudates and Transudates ; Macula Lutea/diagnostic imaging/blood supply/pathology ; },
abstract = {PURPOSE: To assess differences in choriocapillaris (CC) and macular neovascularization (MNV) optical coherence tomography angiography quantitative parameters between long-term persistently nonexudative MNVs (NE-MNVs) and long-term activated NE-MNVs in age-related macular degeneration.<br><br>METHODS: Age-related macular degeneration patients with treatment-na&#xef;ve NE-MNVs with >2 years of follow-up and no evidence of exudation within the first 6 months from diagnosis were retrospectively recruited. Two groups were considered according to the occurrence (EX group) or not (NE group) of exudation within the first 2 years of follow-up. Segmentation of the MNV and of the perilesional CC were obtained from enface optical coherence tomography angiography acquisitions at diagnosis and at 6-month follow-up. OCT B-scan images of the MNV were also collected. Fractal ratio was defined as the ratio between MNV fractal dimension (FrD) and CC FrD.<br><br>RESULTS: Fifty (50) eyes were included (20 EX group and 30 NE group). EX group showed higher flow deficit density and flow deficit number at the 6-month follow-up. It also showed higher MNV FrD, lower CC FrD, and higher fractal ratio at the 6-month follow-up. The fractal ratio significantly increased at 6-month acquisitions in the EX group, showing an area under the ROC curves of 0.887 (95% CI 0.869-0.922).<br><br>CONCLUSION: Fractal ratio at 6 months can predict exudation risk of MNV within 2 years from diagnosis. This suggests increased structural complexity of the NE-MNV accompanied by progressive capillary rarefaction of the perilesional CC as a key driving factor for the development of exudation in NE-MNV.},
}
@article {pmid39287235,
year = {2024},
author = {Wang, T and Huang, C and Li, J and Wu, X and Fu, X and Hu, Y and Wu, G and Yang, C and Chen, S},
title = {Causal influence of plasma metabolites on age-related macular degeneration: A Mendelian randomization study.},
journal = {Medicine},
volume = {103},
number = {37},
pages = {e39400},
pmid = {39287235},
issn = {1536-5964},
mesh = {Humans ; *Macular Degeneration/blood/genetics ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Polymorphism, Single Nucleotide ; Male ; Female ; Aged ; },
abstract = {Using genome-wide association study data from European populations, this research clarifies the causal relationship between plasma metabolites and age-related macular degeneration (AMD) and employs Metabo Analyst 5.0 for enrichment analysis to investigate their metabolic pathways. Employing Mendelian randomization analysis, this study leveraged single nucleotide polymorphisms significantly associated with plasma metabolites as instrumental variables. This approach established a causal link between metabolites and AMD. Analytical methods such as inverse-variance weighted, Mendelian randomization-Egger, and weighted median were applied to validate causality. Mendelian Randomization Pleiotropy Residual Sum and Outlier was utilized for outlier detection and correction, and Cochran's Q test was conducted to assess heterogeneity. To delve deeper into the metabolic characteristics of AMD, metabolic enrichment analysis was performed using Metabo Analyst 5.0. These combined methods provided a robust framework for elucidating the metabolic underpinnings of AMD. The 2-sample MR analysis, after meticulous screening, identified causal relationships between 88 metabolites and AMD. Of these, 16 metabolites showed a significant causal association. Following false discovery rate correction, 3 metabolites remained significantly associated, with androstenediol (3 beta, 17 beta) disulfate (2) exhibiting the most potent protective effect against AMD. Further exploration using Metabo Analyst 5.0 highlighted 4 metabolic pathways potentially implicated in AMD pathogenesis. This pioneering MR study has unraveled the causal connections between plasma metabolites and AMD. It identified several metabolites with a causal impact on AMD, with 3 maintaining significance after FDR correction. These insights offer robust causal evidence for future clinical applications and underscore the potential of these metabolites as clinical biomarkers in AMD screening, treatment, and prevention strategies.},
}
@article {pmid39285939,
year = {2024},
author = {Taskintuna, K and Bhat, MA and Shaikh, T and Hum, J and Golestaneh, N},
title = {Sex-dependent regulation of retinal pigment epithelium and retinal function by Pgc-1α.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1442079},
pmid = {39285939},
issn = {1662-5102},
abstract = {Age-related macular degeneration (AMD) is a major cause of blindness that affects people over 60. While aging is the prominent factor in AMD, studies have reported a higher prevalence of AMD in women compared to age-matched men. Higher levels of the innate immune response's effector proteins complement factor B and factor I were also found in females compared to males in intermediate AMD. However, the mechanisms underlying these differences remain elusive. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a key regulator of mitochondrial biogenesis and metabolic pathways. Previously, we showed that Pgc-1α repression and high-fat diet induce drastic AMD-like phenotypes in mice. Our recent data revealed that Pgc-1α repression alone can also induce retinal pigment epithelium (RPE) and retinal dysfunction in mice, and its inhibition in vitro results in lipid droplet accumulation in human RPE. Whether sex is a contributing factor in these phenotypes remains to be elucidated. Using electroretinography, we demonstrate that sex could influence RPE function during aging independent of Pgc-1α in wild-type (WT) mice. We further show that Pgc-1α repression exacerbates RPE and retinal dysfunction in females compared to aged-match male mice. Gene expression analyses revealed that Pgc-1α differentially regulates genes related to antioxidant enzymes and mitochondrial dynamics in males and females. RPE flat mounts immunolabeled with TOMM20 and DRP1 indicated a sex-dependent role for Pgc-1α in regulating mitochondrial fission. Analyses of mitochondrial network morphology suggested sex-dependent effects of Pgc-1α repression on mitochondrial dynamics. Together, our study demonstrates that inhibition of Pgc-1α induces a sex-dependent decline in RPE and retinal function in mice. These observations on the sex-dependent regulation of RPE and retinal function could offer novel insights into targeted therapeutic approaches for age-related RPE and retinal degeneration.},
}
@article {pmid39285124,
year = {2024},
author = {Thinggaard, BS and Hansen, K and Dinesen, F and Pedersen, MK and Morsø, L and Subhi, Y and Grauslund, J and Stokholm, L},
title = {The I-OPTA Questionnaire: A National Assessment of Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {12},
pages = {3035-3046},
pmid = {39285124},
issn = {2193-8245},
support = {00041038//Velux Fonden/ ; },
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible vision loss in developed countries. However, a significant gap persists in understanding this population, exacerbated by their advanced age and visual impairments, which can hinder research participation and access to healthcare. The purpose of this study was to describe the content of the questionnaire and the participating patients with nAMD.<br><br>METHODS: The survey includes patients diagnosed with nAMD who had previously received treatment or were currently undergoing intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Participants were recruited using various methods, as reaching out to patients who are no longer receiving treatment poses a particular challenge. A patient and public advisory board assisted throughout the study period.<br><br>RESULTS: Of the 713 electronic invitations sent out, 494 (69.3%) patients responded to the questionnaire, with an additional 57 responses obtained through e-mail or telephone interviews. Due to the exclusion of 16 responses, there were a total of 535 valid responses, including 176 from patients previously treated and 359 from those currently undergoing treatment for nAMD. The median age of respondents was 79.9&#xa0;years (interquartile range [IQR] 75.5-84.7), with 59.8% being women. Among them, 53.2% were married, while 43.1% lived alone.<br><br>CONCLUSIONS: Data from the I-OPTA (Identification of Patient-Reported Barriers in Treatment for nAMD) questionnaire allows future exploration of patients who are no longer receiving treatment, patients' knowledge about preventive measures, and the impact of nAMD on visual function and quality of life. Future research, including studies that integrate data from corresponding retinal images and Danish national registers, has the potential to generate invaluable knowledge, providing benefits to both patients and healthcare professionals.},
}
@article {pmid39283969,
year = {2025},
author = {Hasan Zilani, MN and Nahar, N and Shome, A and Tareq, MMI and Biswas, P and Bibi, S and Alshammari, A and Albekairi, NA and Alqahtani, HM and Hasan, MN},
title = {Crotalaria quinquefolia L. Revealed as a Potential Source of Neuropharmacophore in Both Experimental and Computational Studies.},
journal = {Chemistry &amp; biodiversity},
volume = {22},
number = {1},
pages = {e202401257},
doi = {10.1002/cbdv.202401257},
pmid = {39283969},
issn = {1612-1880},
support = {RSPD2024R1035//Researchers Supporting Project/ ; ID: 22-40//Ministry of Posts, Telecommunications and Information Technology, Department of Information and Communication Technology, Bangladesh/ ; Grant: MoST/2021-22/BS-277//Ministry of Science and Technology, Bangladesh/ ; RSPD2024R1035//Ministry of Science and Technology, Bangladesh/ ; //King Saud University, Riyadh, Saudi Arabia/ ; },
mesh = {Animals ; Mice ; *Antioxidants/pharmacology/chemistry/isolation &amp; purification ; *Plant Extracts/chemistry/pharmacology/isolation &amp; purification ; *Crotalaria/chemistry ; Molecular Docking Simulation ; Maze Learning/drug effects ; Male ; },
abstract = {Herbal remedies have shown great promise for improving human health. The plant Crotalaria quinquefolia is used in folk medicine to cure different diseases, including scabies, fever, discomfort, and lung infections. The present research was designed to explore bioactive compounds and evaluate the neuropharmacological effects of C. quinquefolia extract through in vivo and in silico approaches. Different secondary metabolites as well as the antioxidant activity were measured. Furthermore, chemical compounds were identified by HPLC and GCMS analysis. The neuropharmacological activity was examined by hole cross, hole board, open field, Y-maze, elevated plus maze, and thiopental sodium induced sleeping time tests in mice at doses of 100 mg/kg and 200 mg/kg b.w. (p.o). Besides, an in-silico study was performed on proteins related to Alzheimer disease. The extract showed a significant content of secondary metabolites and antioxidant potential. The in-silico analysis showed that myricetin, quercetin, rutin, and kaempferol have good binding affinity with studied proteins, and QSAR studies revealed potential benefits for treating dementia, and age-related macular degeneration. The findings of the present neurological activity collectively imply that the extract has strong CNS depressant and anxiolytic activity. Therefore, C. quinquefolia can be a potential source of compounds to treat Alzheimer disease.},
}
@article {pmid39283829,
year = {2024},
author = {Ellervik, C and Boulakh, L and Teumer, A and Marouli, E and Kuś, A and Buch Hesgaard, H and Heegaard, S and Blankers, L and Sterenborg, R and Åsvold, BO and Winkler, TW and Medici, M and Kjaergaard, AD and , },
title = {Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.},
journal = {Thyroid : official journal of the American Thyroid Association},
volume = {34},
number = {11},
pages = {1414-1423},
pmid = {39283829},
issn = {1557-9077},
support = {R01 EY022310/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; Female ; Male ; *Diabetes Mellitus, Type 2/genetics/epidemiology ; *Cataract/genetics ; *Macular Degeneration/genetics ; Thyrotropin/blood ; Diabetic Retinopathy/genetics/epidemiology ; Diabetes Mellitus, Type 1/genetics ; Genome-Wide Association Study ; Thyroxine/blood ; Thyroid Gland/physiopathology ; Hypothyroidism/genetics/epidemiology ; Hyperthyroidism/genetics ; Polymorphism, Single Nucleotide ; Glaucoma, Open-Angle/genetics/epidemiology ; Risk Factors ; Aged ; },
abstract = {Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10[-4]), cataract (p = 3 × 10[-3]), and T1D (p = 1 × 10[-3]), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10[-4]). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10[-3]). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.},
}
@article {pmid39282576,
year = {2024},
author = {Guan, JX and Wang, YL and Wang, JL},
title = {How Advanced are Nanocarriers for Effective Subretinal Injection?.},
journal = {International journal of nanomedicine},
volume = {19},
number = {},
pages = {9273-9289},
pmid = {39282576},
issn = {1178-2013},
mesh = {Humans ; Animals ; *Drug Carriers/chemistry ; Injections, Intraocular ; Retina ; Retinal Diseases/therapy/drug therapy ; Nanoparticles/chemistry ; Drug Delivery Systems/methods ; Genetic Vectors/administration &amp; dosage/genetics ; Macular Degeneration/therapy ; },
abstract = {Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment of neovascular age-associated macular degeneration (nAMD) and sub-macular hemorrhage (SMH) caused by nAMD, as well as various types of hereditary retinopathies (IRD) such as Stargardt's disease (STGD), retinitis pigmentosa (RP), and a series of fundus diseases such as Leber's congenital dark haze (LCA), choroidal defects, etc. The commonly used carriers of SR injection are mainly divided into viral and non-viral vectors. Leber's congenital amaurosis (LCA), choroidal agenesis, and a series of other fundus diseases are also commonly treated using SR injection. The commonly used vectors for SR injection are divided into two categories: viral vectors and non-viral vectors. Viral vectors are a traditional class of SR injection drug carriers that have been extensively studied in clinical treatment, but they still have many limitations that cannot be ignored, such as poor reproduction efficiency, small loading genes, and triggering of immune reactions. With the rapid development of nanotechnology in the treatment of ocular diseases, nanovectors have become a research hotspot in the field of non-viral vectors. Nanocarriers have numerous attractive properties such as low immunogenicity, robust loading capacity, stable structure, and easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, and more flexible indications. In recent years, there has been a growing interest in nanocarriers, which has led to significant advancements in the treatment of ocular diseases. Nanocarriers have not only successfully addressed clinical problems that viral vectors have failed to overcome but have also introduced new therapeutic possibilities for certain classical disease types. Nanocarriers offer undeniable advantages over viral vectors. This review discusses the advantages of subretinal (SR) injection, the current status of research, and the research hotspots of gene therapy with viral vectors. It focuses on the latest progress of nanocarriers in SR injection and enumerates the limitations and future perspectives of nanocarriers in the treatment of fundus lesions. Furthermore, this review also covers the research progress of nanocarriers in the field of subretinal injection and highlights the value of nanocarrier-mediated SR injection in the treatment of fundus disorders. Overall, it provides a theoretical basis for the application of nanocarriers in SR injection.},
}
@article {pmid39281979,
year = {2024},
author = {Finzi, A and Ottoboni, S and Cellini, M and Corcioni, B and Gaudiano, C and Fontana, L},
title = {Color Doppler Imaging, Endothelin-1, Corneal Biomechanics and Scleral Rigidity in Asymmetric Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {2583-2591},
pmid = {39281979},
issn = {1177-5467},
abstract = {PURPOSE: Age-related macular degeneration (AMD) presents a multifaceted etiopathogenesis involving ischemic, inflammatory, and genetic components. This study investigates the correlation between ocular hemodynamics, scleral rigidity (SR), and plasma endothelin-1 (ET1) levels in treatment-naive patients with asymmetrical AMD.<br><br>PATIENTS AND METHODS: This study included 20 treatment-naive patients (12 females and 8 males) with an average age of 76.4 &#xb1; 3.7 years, who presented with AMD with neovascular membrane formation (nAMD) in one eye, and intermediate grade 2 AMD (iAMD) in the other eye. The control group consisted of 20 healthy subjects (13 females and 7 males) with a mean age of 74.7 &#xb1; 3.9 years. All patients and healthy controls underwent color Doppler imaging (i) of the ophthalmic artery (OA), short posterior ciliary arteries (SPCAs), and central retinal artery (CRA); Plasma ET-1 levels were measured for all patients and healthy subjects. Corneal biomechanics were assessed using an Ocular Response Analyzer and two indices were obtained: corneal hysteresis (CH) and corneal resistance factor (CRF).<br><br>RESULTS: Results showed reduced blood flow velocities and increased resistance indices in AMD eyes, particularly affecting the short posterior ciliary arteries. According to mechanical theory, ARMD eyes exhibited elevated scleral rigidity and corneal resistance factor compared to controls, with a notable rise in SR in neovascular AMD (nAMD) eyes. As per the chronic subacute inflammation theory, plasma ET-1 levels were significantly higher in AMD patients, correlating with abnormal SPCAs blood flow and increased resistance indices.<br><br>CONCLUSION: Findings suggest a multifactorial etiology of AMD involving an increase of ET-1 plasma levels with biomechanic damages of corneal and scleral tissue in nAMD.},
}
@article {pmid39281400,
year = {2023},
author = {Panahi, P and Kabir, A and Falavarjani, KG},
title = {Age-Related Macular Degeneration Prevalence and its Risk Factors in Iran: A Systematic Review and Meta-Analysis Study.},
journal = {Journal of current ophthalmology},
volume = {35},
number = {4},
pages = {305-312},
pmid = {39281400},
issn = {2452-2325},
abstract = {PURPOSE: To estimate the prevalence of age-related macular degeneration (AMD) and determine its risk factors in Iran.<br><br>METHODS: A comprehensive electronic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar, with no restrictions on time or language of publication. Eleven studies meeting the eligibility criteria were included. Six studies with a total sample size of 9930 were included in the meta-analysis to calculate the overall prevalence of AMD in Iran. Meta-analysis was performed using Stata/MP version 15.0. Risk of bias assessment was carried out based on the Newcastle-Ottawa Scale.<br><br>RESULTS: All participants in the studies were over 40 years old. The pooled prevalence of AMD was estimated to be 9.9% (95% confidence interval [CI]: 6.3%-13.5%). After accounting for publication bias, this estimated decreased to 6.4% (95% CI: 4%-10.2%). Smoking (odds ratio [OR]: 1.781; 95% CI: 1.152-2.756), hypertension (HTN) (OR: 1.512; 95% CI: 1.119-2.044), diabetes mellitus (DM) (OR: 1.545; 95% CI: 1.088-2.194), and hyperlipidemia (OR: 1.512; 95% CI: 1.055-2.165) were identified as AMD risk factors.<br><br>CONCLUSION: Based on the results of the present review, the prevalence of AMD in the Iranian population over 40 years of age is estimated to be 6.4%, and having a history of smoking, HTN, DM, and hyperlipidemia are identified as risk factors of AMD in Iran. Further original studies are needed to draw more accurate conclusions.},
}
@article {pmid39281396,
year = {2023},
author = {Abdolalizadeh, P and Falavarjani, KG},
title = {The Correlation of Global Burden of Vision Impairment and Ambient Atmospheric Fine Particulate Matter.},
journal = {Journal of current ophthalmology},
volume = {35},
number = {4},
pages = {387-394},
pmid = {39281396},
issn = {2452-2325},
abstract = {PURPOSE: To assess the correlation between the worldwide burden of vision impairment (VI) and fine particulate matter (PM) 2.5.<br><br>METHODS: In this retrospective cross-sectional study, global and national prevalence and disability-adjusted lost year (DALY) numbers and rates of total VI, glaucoma, cataract, and age-related macular degeneration (AMD) were obtained from the Global Burden of Disease database. The global and national levels of PM2.5 levels were also extracted. The main outcome measures were the correlation of PM2.5 levels with total VI and three ocular diseases in different age, sex, and socioeconomic subgroups.<br><br>RESULTS: In 2019, the worldwide prevalence of total VI and exposure level of PM2.5 was 9.6% (95% uncertainty interval: 8.0-11.3) and 42.5 &#x3bc;g/m[3], respectively. The national age-standardized prevalence rates of total VI (r p = 0.52, P < 0.001), glaucoma (r p = 0.65, P < 0.001), AMD (r p = 0.67, P < 0.001), and cataract (r p = 0.44, P < 0.001) have a positive correlation with PM2.5 levels. In addition, the national age-standardized DALY rates of total VI (r p = 0.62, P < 0.001), glaucoma (r p = 0.62, P < 0.001), AMD (r p = 0.54, P < 0.001), and cataract (r p = 0.45, P < 0.001) significantly correlated with PM2.5 levels. The correlations remained significant in different age, sex, and sociodemographic subgroups.<br><br>CONCLUSION: National prevalence rates of VI and three major ocular diseases correlate significantly with PM2.5 exposure levels, worldwide.},
}
@article {pmid39281109,
year = {2024},
author = {Xu, JF and Wang, YP and Liu, XH},
title = {Novel fabrication of anti-VEGF drug ranibizumab loaded PLGA/PLA co-polymeric nanomicelles for long-acting intraocular delivery in the treatment of age-related macular degeneration therapy.},
journal = {Regenerative therapy},
volume = {26},
number = {},
pages = {620-634},
pmid = {39281109},
issn = {2352-3204},
abstract = {Age associated macular degeneration is the 3rd primary cause of blind fundus diseases globally. A reliable and long-lasting method of intraocular drug delivery is still needed. Herein, this study was aim to develop the novel fabrication of ranibizumab loaded co-polymeric nanomicelles (Rabz-CP-NMs) for AMD. The CMC of co-polymeric nanomicelles was determined to be low, at 6.2 μg/ml. The ring copolymerization method was employed to fabricate the NMs and characterize via FTIR, XRD, TEM, DLS and Zeta potential. Rabz-CP-NMs was spherical shape with 10-50 nm in size. Stable and prolonged drug release was achieved with the Rabz from CP-NMs at 48 h. D407 and ARPE19 ocular cell lines showed dose-dependent cell viability with Rabz-CP-NMs. The Rabz-CP-NMs also had less toxicity, higher uptake, lower cell death and prolonged VEGF-A inhibition, as shown by cytoviability assay. Thus, Rabz-CP-NMs were safe for ocular use, suggesting that could be used to improve intraocular AMD treatment.},
}
@article {pmid39279719,
year = {2024},
author = {Zumaraga, MP and Desmarchelier, C and Gleize, B and Nowicki, M and Ould-Ali, D and Borel, P},
title = {Characterization of the interindividual variability of lutein and zeaxanthin concentrations in the adipose tissue of healthy male adults and identification of combinations of genetic variants associated with it.},
journal = {Food &amp; function},
volume = {15},
number = {19},
pages = {9995-10006},
doi = {10.1039/d4fo03087g},
pmid = {39279719},
issn = {2042-650X},
mesh = {Adult ; Humans ; Male ; Middle Aged ; Young Adult ; *Adipose Tissue/metabolism ; Genotype ; *Lutein/metabolism ; *Polymorphism, Single Nucleotide ; *Zeaxanthins/metabolism ; },
abstract = {Lutein (L) and zeaxanthin (Z) are involved in visual function and could prevent age-related macular degeneration and chronic diseases and improve cognitive performances. Adipose tissue is the main storage site for these xanthophylls (Xanth). The factors affecting their concentrations in this tissue remain poorly understood but in animal models, genetic variations in apolipoprotein E and β-carotene oxygenase 2 have been associated with adipose tissue L concentration. Therefore, the aims of this study were to better characterize the interindividual variability of adipose tissue Xanth concentration and to identify single nucleotide polymorphisms (SNPs) associated with it. Periumbilical subcutaneous adipose tissue samples were collected on 6 occasions in 42 healthy adult males and L and Z concentrations were measured by HPLC. Participants had their whole genome genotyped and the associations of 3589 SNPs in 49 candidate genes with the concentrations of L and Z were measured. Mean L and Z concentrations were 281 ± 27 and 150 ± 14 nmol g[-1] proteins, respectively. There was no significant correlation between plasma and adipose tissue Xanth concentrations, although the correlation for L approached significance (Pearson's r = 0.276, p = 0.077). Following univariate filtering, 109 and 97 SNPs were then entered into a partial least squares regression analysis to identify the combination of SNPs that explained best adipose tissue concentration of L and Z, respectively. A combination of 7 SNPs in ELOVL5, PPARG, ISX and ABCA1, explained 58% of the variability in adipose tissue L concentration while 11 SNPs located in or near PPARG, ABCA1, ELOVL5, CXCL8, IRS1, ISX, MC4R explained 53% of the variance in adipose tissue Z concentration. This suggests that some genetic variations influence the concentrations of these Xanth in adipose tissue and could therefore indirectly influence the health effects of these compounds. Clinical Trial Registry: https://ClinicalTrials.gov registration number NCT02100774.},
}
@article {pmid39279009,
year = {2024},
author = {Nanegrungsunk, O and Corradetti, G and Phinyo, P and Choovuthayakorn, J and Sadda, SR},
title = {Relationship between hypertransmission defect size and progression in eyes with intermediate age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {18},
pages = {3488-3494},
pmid = {39279009},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Retrospective Studies ; *Disease Progression ; Aged ; *Retinal Pigment Epithelium/pathology ; *Macular Degeneration/physiopathology/diagnosis ; Aged, 80 and over ; Visual Acuity/physiology ; Middle Aged ; Fluorescein Angiography/methods ; Atrophy ; },
abstract = {OBJECTIVES: To determine the associations between the presence of various-sized hypertransmission defects (hyperTDs) and progression to incomplete retinal pigment epithelial (RPE) and outer retinal atrophy (iRORA) and complete RORA (cRORA) in eyes with intermediate age-related macular degeneration (iAMD).<br><br>METHODS: Optical coherence tomography (OCT) data from consecutive iAMD patients, were retrospectively reviewed. All of iAMD eyes with or without iRORA (but not cRORA) at baseline were included. Graders evaluated the presence of hyperTDs at baseline (small: 63-124&#x2009;&#xb5;m; medium: 125-249&#x2009;&#xb5;m; large: &#x2265;&#xa0;250&#x2009;&#xb5;m in diameter on choroidal en face OCT) and the progression two years later.<br><br>RESULTS: Of the 145 eyes that not developed neovascular AMD at two years, the eyes that progressed to or developed iRORA or cRORA included 13 eyes (10.7%), 5 eyes (83.3%), 9 eyes (81.8%), and 6 eyes (85.7%) in the groups with no, small, medium, and large hyperTDs at baseline, respectively (P-value&#x2009;<&#x2009;0.001). The odds ratios (95% CI) for progression were 41.6 (4.5-383.6), 37.4 (7.3-192.0), and 49.9 (5.6-447.1) in the small, medium, and large hyperTDs groups, compared to no hyperTDs (P-value &#x2264; 0.001). Eyes with &#x2265;&#xa0;2 hyperTDs also showed more frequent progression than eyes with one or no hyperTDs (100% vs. 16.4%; P-value&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: While most iAMD eyes with no hyperTDs remained stable on OCT over two years, eyes with hyperTDs of any size appeared to be at a higher risk for progression. HyperTDs may provide an important OCT biomarker for identifying high-risk iAMD patients.},
}
@article {pmid39277630,
year = {2024},
author = {Nassisi, M and Mainetti, C and Paparella, GR and Belloni Baroni, L and Milella, P and Leone, G and Galli, D and Pozzo Giuffrida, F and Dell'Arti, L and Mapelli, C and Casalino, G and Viola, F},
title = {Short-term efficacy of photobiomodulation in early and intermediate age-related macular degeneration: the PBM4AMD study.},
journal = {Eye (London, England)},
volume = {38},
number = {18},
pages = {3467-3472},
pmid = {39277630},
issn = {1476-5454},
mesh = {Humans ; *Visual Acuity/physiology ; Prospective Studies ; Female ; Male ; Aged ; *Contrast Sensitivity/physiology ; *Low-Level Light Therapy/methods ; Aged, 80 and over ; Middle Aged ; Tomography, Optical Coherence ; Retinal Drusen/physiopathology/radiotherapy ; Macular Degeneration/radiotherapy/physiopathology ; Treatment Outcome ; Wet Macular Degeneration/radiotherapy/physiopathology ; },
abstract = {OBJECTIVES: This independent prospective study evaluated the short-term effects and safety of photobiomodulation (PBM) in early and intermediate age-related macular degeneration.<br><br>METHODS: patients were treated with PBM in one eye. Functional parameters and drusen volume were measured at one (W4), three- (W12) and six-months (W24) after PBM.<br><br>RESULTS: The study included 38 subjects who completed the PBM protocol. Two patients developed macular neovascularization during the study period. Best corrected visual acuity improved from 77.82&#x2009;&#xb1;&#x2009;5.83 ETDRS letters at baseline to 82.44&#x2009;&#xb1;&#x2009;5.67 at W12 (p&#x2009;<&#x2009;0.01), then declined to 80.05&#x2009;&#xb1;&#x2009;5.79 at W24 (p&#x2009;<&#x2009;0.01 vs. baseline). Low luminance visual acuity showed a similar pattern, improving from 61.18&#x2009;&#xb1;&#x2009;8.58 ETDRS letters at baseline to 66.33&#x2009;&#xb1;&#x2009;8.55 at W12 (p&#x2009;<&#x2009;0.01), and decreasing to 62.05&#x2009;&#xb1;&#x2009;9.71 at W24 (p&#x2009;=&#x2009;0.02). Contrast sensitivity improved at W12 (20.11&#x2009;&#xb1;&#x2009;9.23&#xa0;ETDRS letters, p&#x2009;<&#x2009;0.01), but returned to baseline by W24 (16.45&#x2009;&#xb1;&#x2009;9.12, p&#x2009;=&#x2009;0.5). Scotopic microperimetry showed a decrease in mean absolute retinal sensitivity from 9.24&#x2009;&#xb1;&#x2009;3.44&#x2009;dB to 7.47&#x2009;&#xb1;&#x2009;4.41&#x2009;dB at W24 (p&#x2009;<&#x2009;0.01), while relative sensitivity decreased only at W24 (p&#x2009;=&#x2009;0.04). Drusen volume decreased at W4 (0.018&#x2009;&#xb1;&#x2009;0.009 mm3, p&#x2009;<&#x2009;0.01) and W12 (0.017&#x2009;&#xb1;&#x2009;0.009 mm3, p&#x2009;<&#x2009;0.01), with a slight increase at W24 (0.019&#x2009;&#xb1;&#x2009;0.012 mm3, p&#x2009;=&#x2009;0.154).<br><br>CONCLUSIONS: PBM resulted in temporary improvements in visual function and a reduction in drusen volume, but these effects were not sustained at six months. The long-term efficacy and impact on disease progression are uncertain, necessitating further research to confirm these findings and determine optimal patient selection.},
}
@article {pmid39276938,
year = {2024},
author = {Hass, DT and Pandey, K and Engel, A and Horton, N and Haydinger, CD and Robbings, BM and Lim, RR and Sadilek, M and Zhang, Q and Gulette, GA and Li, A and Xu, L and Miller, JML and Chao, JR and Hurley, JB},
title = {Acetyl-CoA carboxylase inhibition increases retinal pigment epithelial cell fatty acid flux and restricts apolipoprotein efflux.},
journal = {The Journal of biological chemistry},
volume = {300},
number = {10},
pages = {107772},
pmid = {39276938},
issn = {1083-351X},
support = {R01 EY006641/EY/NEI NIH HHS/United States ; R01 EY034364/EY/NEI NIH HHS/United States ; S10 OD021562/OD/NIH HHS/United States ; K08 EY033420/EY/NEI NIH HHS/United States ; K99 EY034881/EY/NEI NIH HHS/United States ; R24 HD000836/HD/NICHD NIH HHS/United States ; R01 EY017863/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Acetyl-CoA Carboxylase/metabolism ; Humans ; Animals ; *Fatty Acids/metabolism ; Mice ; Epithelial Cells/metabolism/drug effects/pathology ; Apolipoproteins E/metabolism/genetics ; Enzyme Inhibitors/pharmacology ; Macular Degeneration/metabolism/pathology/drug therapy ; },
abstract = {Lipid-rich deposits called drusen accumulate under the retinal pigment epithelium (RPE) in the eyes of patients with age-related macular degeneration and Sorsby's fundus dystrophy (SFD). Drusen may contribute to photoreceptor degeneration in these blinding diseases. Stimulating β-oxidation of fatty acids could decrease the availability of lipid with which RPE cells generate drusen. Inhibitors of acetyl-CoA carboxylase (ACC) stimulate β-oxidation and diminish lipid accumulation in fatty liver disease. In this report, we test the hypothesis that an ACC inhibitor, Firsocostat, can diminish lipid deposition by RPE cells. We probed metabolism and cellular function in mouse RPE-choroid tissue and human RPE cells. We used [13]C6-glucose, [13]C16-palmitate, and gas chromatography-linked mass spectrometry to monitor effects of Firsocostat on glycolytic, Krebs cycle, and fatty acid metabolism. We quantified lipid abundance, apolipoprotein E levels, and vascular endothelial growth factor release using liquid chromatography-mass spectrometry, ELISAs, and immunostaining. RPE barrier function was assessed by trans-epithelial electrical resistance (TEER). Firsocostat-mediated ACC inhibition increases β-oxidation, decreases intracellular lipid levels, diminishes lipoprotein release, and increases TEER. When human serum or outer segments are used to stimulate lipoprotein release, fewer lipoproteins are released in the presence of Firsocostat. In a culture model of SFD, Firsocostat stimulates fatty acid oxidation, increases TEER, and decreases apolipoprotein E release. We conclude that Firsocostat remodels RPE metabolism and can limit lipid deposition. This suggests that ACC inhibition could be an effective strategy for diminishing pathologic drusen in the eyes of patients with age-related macular degeneration or SFD.},
}
@article {pmid39276227,
year = {2024},
author = {Terheyden, JH and Mauschitz, MM and Wintergerst, MWM and Chang, P and Herrmann, P and Liegl, R and Ach, T and Finger, RP and Holz, FG},
title = {[Digital remote monitoring of chronic retinal conditions-A clinical future tool? : Remote monitoring of chronic retinal conditions].},
journal = {Die Ophthalmologie},
volume = {121},
number = {10},
pages = {826-834},
pmid = {39276227},
issn = {2731-7218},
mesh = {Humans ; *Telemedicine ; Chronic Disease ; *Retinal Diseases/diagnosis ; Forecasting ; Tomography, Optical Coherence/methods ; Monitoring, Physiologic/methods ; },
abstract = {BACKGROUND: In view of the predicted increase in incidence and prevalence of chronic retinal diseases and undersupply of care in the population, telemedicine could contribute to reducing access barriers to healthcare and improving the results of treatment.<br><br>OBJECTIVE: A literature review on remote monitoring of chronic retinal diseases was carried out.<br><br>MATERIAL AND METHODS: The medical literature was searched for publications on remote monitoring of chronic retinal diseases. The results were compiled in a&#xa0;narrative overview.<br><br>RESULTS: The four main topics in the literature are: validation studies, implementation strategies, acceptance/target group analyses and health economic analyses. Remote monitoring systems are based on visual function tests, imaging or patient reports and have been particularly investigated in age-related macular degeneration (AMD) and diabetic eye disease (DED). Studies indicate positive effects regarding an optimization of clinical care and a&#xa0;favorable safety profile but randomized controlled trials are lacking for the majority of monitoring tools.<br><br>CONCLUSION: Remote monitoring could complement existing care structures for patients with chronic retinal diseases, especially AMD and DED. Promising systems are based on hyperacuity or optical coherence tomography, while patient-reported data are not commonly used; however, there is currently insufficient evidence justifying the use of remote monitoring systems in chronic retinal diseases in Europe and more research on the validation of remote monitoring systems is needed.},
}
@article {pmid39275167,
year = {2024},
author = {Schiano, E and Vaccaro, S and Scorcia, V and Carnevali, A and Borselli, M and Chisari, D and Guerra, F and Iannuzzo, F and Tenore, GC and Giannaccare, G and Novellino, E},
title = {From Vineyard to Vision: Efficacy of Maltodextrinated Grape Pomace Extract (MaGPE) Nutraceutical Formulation in Patients with Diabetic Retinopathy.},
journal = {Nutrients},
volume = {16},
number = {17},
pages = {},
pmid = {39275167},
issn = {2072-6643},
mesh = {Humans ; *Diabetic Retinopathy/drug therapy ; *Dietary Supplements ; *Vitis/chemistry ; Male ; Female ; *Plant Extracts/pharmacology ; Middle Aged ; *Visual Acuity/drug effects ; *Oxidative Stress/drug effects ; *Polysaccharides/pharmacology ; Aged ; Treatment Outcome ; Lipoproteins, LDL/blood ; Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; },
abstract = {Despite recent advances, pharmacological treatments of diabetic retinopathy (DR) do not directly address the underlying oxidative stress. This study evaluates the efficacy of a nutraceutical formulation based on maltodextrinated grape pomace extract (MaGPE), an oxidative stress inhibitor, in managing DR. A 6-month, randomized, placebo-controlled clinical trial involving 99 patients with mild to moderate non-proliferative DR was conducted. The MaGPE group showed improvement in best-corrected visual acuity (BCVA) values at T3 (p < 0.001) and T6 (p < 0.01), a reduction in CRT (at T3 and T6, both p < 0.0001) and a stabilization of vascular perfusion percentage, with slight increases at T3 and T6 (+3.0% and +2.7% at T3 and T6, respectively, compared to baseline). Additionally, the levels of reactive oxygen metabolite derivatives (dROMs) decreased from 1100.6 ± 430.1 UCARR at T0 to 974.8 ± 390.2 UCARR at T3 and further to 930.6 ± 310.3 UCARR at T6 (p < 0.05 vs. T0). Similarly, oxidized low-density lipoprotein (oxLDL) levels decreased from 953.9 ± 212.4 µEq/L at T0 to 867.0 ± 209.5 µEq/L at T3 and markedly to 735.0 ± 213.7 µEq/L at T6 (p < 0.0001 vs. T0). These findings suggest that MaGPE supplementation effectively reduces retinal swelling and oxidative stress, contributing to improved visual outcomes in DR patients.},
}
@article {pmid39275082,
year = {2024},
author = {Liu, C and Xu, Q and Liu, Y and Song, M and Cao, X and Du, X and Yan, H},
title = {Metabolomic Analysis of Carotenoids Biosynthesis by Sphingopyxis sp. USTB-05.},
journal = {Molecules (Basel, Switzerland)},
volume = {29},
number = {17},
pages = {},
pmid = {39275082},
issn = {1420-3049},
support = {21677011//National Natural Science Foundation of China/ ; 2022YFE0118800//National Key Research and Development Program of China/ ; },
mesh = {*Carotenoids/metabolism ; *Metabolomics/methods ; Sphingomonadaceae/metabolism ; Biosynthetic Pathways ; Xanthophylls/metabolism ; Metabolome ; },
abstract = {Carotenoids belonging to the class of tetraterpenoids have extensive applications in medicine, food, nutrition, cosmetics, and feed. Among them, lutein and zeaxanthin can prevent macular degeneration in the elderly, which is very important for protecting vision. Here, we introduce the first metabolomic analysis of Sphingopyxis sp. USTB-05, aiming to shed light on the biosynthesis of carotenoids. Sphingopyxis sp. USTB-05 has the complete methylerythritol 4-phosphate (MEP) pathway and carotenoid biosynthesis pathway, especially involved in the bioconversion of zeaxanthin, violaxanthin, and astaxanthin. Metabolomic profiling identified seven carotenes and six xanthophylls synthesized by Sphingopyxis sp. USTB-05. Zeaxanthin, in particular, was found to be the most abundant, with a content of 37.1 µg/g dry cells. Collectively, the results presented herein greatly enhance our understanding of Sphingopyxis sp. USTB-05 in carotenoids biosynthesis, and thus further accelerate its fundamental molecular investigations and biotechnological applications.},
}
@article {pmid39274532,
year = {2024},
author = {Abu Dail, Y and Seitz, B and Sideroudi, H and Abdin, AD},
title = {Impact of Intra-Retinal Fluids on Changes in Retinal Ganglion Cell and Nerve Fiber Layers in Neovascular AMD under Anti-VEGF Therapy.},
journal = {Journal of clinical medicine},
volume = {13},
number = {17},
pages = {},
pmid = {39274532},
issn = {2077-0383},
abstract = {Purpose: To investigate the influence of intraretinal fluid (IRF) on change in retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (RGCL) and thickness in patients with naive neovascular AMD under anti-VEGF treatment. Design: post hoc analysis. Methods: 97 eyes of 83 patients on continuous therapy with intravitreal anti-vascular endothelial growth factors (anti-VEGF) and a follow-up of 24 months were included. RGCL and RNFL thickness in the perifoveal (-O), parafoveal (PF), and nasal areas and number of injections (IVI) were recorded before the first IVI as well as 1 and 2 years after initiating treatment and compared longitudinally and between groups with and without IRF. Results: The group with IRF at baseline had a higher RNFL thickness at baseline and showed a significant reduction in RNFL-PF between baseline and first and second follow-ups (p < 0.001) but not between first and second follow-ups. The group without IRF showed no significant reduction in RNFL over time. The presence of IRF was not associated with a reduction in RNFL-O or RNFL-nasal. RGCL thickness decreased significantly in both groups with and without IRF after 2 years. Number of IVIs showed no significant correlation to RNFL or RGCL after stratification for the presence of IRF. Conclusions: The presence of IRF has a significant influence on RNFL thickness at baseline as well as on its changes over time during anti-VEGF therapy. The preoperative presence of IRF should be considered when comparing changes in RNFL thickness after IVI.},
}
@article {pmid39274421,
year = {2024},
author = {Campos, A and Mota, C and Caramelo, F and Oliveira, N and Silva, S and Sousa, J},
title = {Inflammation and Vasculitis Related to Brolucizumab.},
journal = {Journal of clinical medicine},
volume = {13},
number = {17},
pages = {},
pmid = {39274421},
issn = {2077-0383},
abstract = {Background/objectives: To compare the prevalence of intra-ocular inflammation (IOI) between brolucizumab and aflibercept in neovascular age-related macular degeneration (nAMD) after intra-vitreal injections (IVI) and to compare the IOI odds ratios (ORs) of both therapies with the prevalence of septic endophthalmitis after IVI that was previously reported in the literature. Methods: A total of 468 IVI of brolucizumab (117 eyes) were compared with 2884 IVI of aflibercept (305 eyes) regarding IOI and occlusive retinal vasculitis (RV) from December 2021 to June 2023 in this retrospective study. The OR was calculated for both anti-VEGF agents and was compared with the relative risk of septic endophthalmitis after IVI. Results: There were four eyes with unilateral IOI related to brolucizumab (3.42%), one presenting uveitis (0.85%), two vitritis (1.71%) and the last one presenting occlusive RV (0.85%), compared with two eyes presenting unilateral IOI (anterior uveitis, 0.66%) and none with RV from the aflibercept cohort. The incidence of IOI per injection with brolucizumab (0.855%) was significantly higher compared with aflibercept (0.069%, p = 0.004). The OR of IOI related to brolucizumab IVI compared with septic endophthalmitis was 20 times greater (1.49 for aflibercept, p = 0.646, versus 20.15 for brolucizumab, p < 0.001). The OR of RV with brolucizumab compared with septic endophthalmitis was 4.6. Conclusion: Data from our department suggest a much higher risk of IOI and occlusive retinal vasculitis after brolucizumab when compared with aflibercept. The risk of IOI and severe sight-threatening complications related to brolucizumab is greater than the risk of septic endophthalmitis after any IVI.},
}
@article {pmid39274287,
year = {2024},
author = {Fukushima, Y and Takahashi, S and Nakamura, M and Inoue, T and Fujieda, Y and Sato, T and Noguchi, S and Tsujikawa, M and Sakaguchi, H and Nishida, K},
title = {An Association between HTRA1 and TGF-β2 in the Vitreous Humor of Patients with Chorioretinal Vascular Diseases.},
journal = {Journal of clinical medicine},
volume = {13},
number = {17},
pages = {},
pmid = {39274287},
issn = {2077-0383},
support = {JPMJFR200S//JST FOREST Program/ ; },
abstract = {Background: The aim of this paper was to investigate the protein concentrations of high-temperature requirement A 1 (HTRA1) and transforming growth factor-β (TGF-β) in the vitreous humor of patients with chorioretinal vascular diseases. Methods: This study measured protein concentrations of HTRA1, TGF-β1-3, and vascular endothelial growth factor A (hereinafter called VEGF) in the vitreous humor from seven eyes of patients with chorioretinal vascular diseases (age-related macular degeneration, diabetic macular edema, and retinal vein occlusion) and six control eyes (idiopathic epiretinal membrane and macular hole). We analyzed the mutual relationship among the protein levels. Results: The protein levels of HTRA1 and VEGF were significantly increased in the chorioretinal vascular disease group compared with the control group (1.57 ± 0.79 ×10-9 mol/mL vs. 0.68 ± 0.79 ×10-9 mol/mL, p = 0.039; 3447.00 ± 3423.47 pg/mL vs. 35.33 ± 79.01 pg/mL, p = 0.046, respectively). TGF-β2 levels were not significantly different between groups (2222.71 ± 1151.25 pg/mL for the chorioretinal vascular disease group vs. 1918.83 ± 744.01 pg/mL for the control group, p = 0.62). The concentration of HTRA1 was strongly associated with TGF-β2 levels in the vitreous humor, independent of VEGF (r = 0.80, p = 0.0010). Conclusions: We revealed that vitreous HTRA1 was increased in patients with chorioretinal vascular diseases and strongly correlated with TGF-β2.},
}
@article {pmid39274255,
year = {2024},
author = {Faatz, H and Lommatzsch, A},
title = {Overview of the Use of Optical Coherence Tomography Angiography in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {17},
pages = {},
pmid = {39274255},
issn = {2077-0383},
abstract = {The aim of this review is to present and discuss the use of optical coherence tomography angiography (OCTA) in age-related macular degeneration (AMD). OCTA is a non-invasive imaging procedure that gives a detailed indirect view of physiological and pathological vessels in the retina and choroid membrane. Compared with dye-based imaging, OCTA provides a segmented presentation of the individual vascular layers and plexuses, thus enabling previously unattainable differentiation and classification of pathological vascular changes within or underneath the retina. In particular, OCTA facilitates early detection of exudative macular neovascularizations (MNV) so that treatment with anti-VEGF medication can be initiated. Moreover, in the context of both screening and therapy monitoring, it is hoped that OCTA can provide more detailed data to enable greater personalization of treatment and follow-up. The image quality of OCTA is, however, susceptible to artifacts, and validation of the results by studies is required. Recent developments have shown constant improvement both in the algorithms for image calculation and avoidance of artifacts and in image quality, so the scope of OCTA will certainly expand with time.},
}
@article {pmid39273697,
year = {2024},
author = {Cebatoriene, D and Vilkeviciute, A and Gedvilaite-Vaicechauskiene, G and Duseikaite, M and Bruzaite, A and Kriauciuniene, L and Zaliuniene, D and Liutkeviciene, R},
title = {The Impact of ARMS2 (rs10490924), VEGFA (rs3024997), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), and IL1B1 (rs1143623) Polymorphisms and Serum Levels on Age-Related Macular Degeneration Development and Therapeutic Responses.},
journal = {International journal of molecular sciences},
volume = {25},
number = {17},
pages = {},
pmid = {39273697},
issn = {1422-0067},
support = {S-MIP-23-96//Research Council of Lithuania under the initiative of Re-searcher Group Projects./ ; },
mesh = {Humans ; *Vascular Endothelial Growth Factor A/genetics/blood ; Male ; Female ; *Macular Degeneration/genetics/drug therapy/blood/pathology ; *Polymorphism, Single Nucleotide ; Aged ; *Interleukin-1beta/genetics/blood ; *Receptors, Tumor Necrosis Factor, Type I/genetics/blood ; Aged, 80 and over ; Genetic Predisposition to Disease ; Middle Aged ; Genotype ; Alleles ; Proteins ; Receptors, Tumor Necrosis Factor, Type II ; },
abstract = {Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective but do not respond optimally in all patients. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the ARMS2 (rs10490924), IL1B1 (rs1143623), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), VEGFA (rs3024997), ARMS2, IL1B1, TNFRSF1B, TNFRSF1A, and VEGFA serum levels in AMD development and treatment efficacy. This study examined the associations of specific genetic polymorphisms and serum protein levels with exudative and early AMD and the response to anti-VEGF treatment. The AA genotype of VEGFA (rs3024997) was significantly associated with a 20-fold reduction in the odds of exudative AMD compared to the GG + GA genotypes. Conversely, the TT genotype of ARMS2 (rs10490924) was linked to a 4.2-fold increase in the odds of exudative AMD compared to GG + GT genotypes. In females, each T allele of ARMS2 increased the odds by 2.3-fold, while in males, the TT genotype was associated with a 5-fold increase. Lower serum IL1B levels were observed in the exudative AMD group compared to the controls. Early AMD patients had higher serum TNFRSF1B levels than controls, particularly those with the GG genotype of TNFRSF1B rs1061622. Exudative AMD patients with the CC genotype of TNFRSF1A rs4149576 had lower serum TNFRSF1A levels compared to the controls. Visual acuity (VA) analysis showed that non-responders had better baseline VA than responders but experienced decreased VA after treatment, whereas responders showed improvement. Central retinal thickness (CRT) reduced significantly in responders after treatment and was lower in responders compared to non-responders after treatment. The T allele of TNFRSF1B rs1061622 was associated with a better response to anti-VEGF treatment under both dominant and additive genetic models. These findings highlight significant genetic and biochemical markers associated with AMD and treatment response. This study found that the VEGFA rs3024997 AA genotype reduces the odds of exudative AMD, while the ARMS2 rs10490924 TT genotype increases it. Lower serum IL1B levels and variations in TNFRSF1B and TNFRSF1A levels were linked to AMD. The TNFRSF1B rs1061622 T allele was associated with better anti-VEGF treatment response. These markers could potentially guide risk assessment and personalized treatment for AMD.},
}
@article {pmid39273005,
year = {2024},
author = {Toppila, M and Ranta-Aho, S and Kaarniranta, K and Hytti, M and Kauppinen, A},
title = {Metformin Alleviates Inflammation and Induces Mitophagy in Human Retinal Pigment Epithelium Cells Suffering from Mitochondrial Damage.},
journal = {Cells},
volume = {13},
number = {17},
pages = {},
pmid = {39273005},
issn = {2073-4409},
support = {297267, 307341, 328443//Research Council of Finland/ ; 5503770//Kuopio University Hospital/ ; foundation grant//Emil Aaltosen S&#xe4;&#xe4;ti&#xf6;/ ; foundation grant//Finnish Cultural Foundation/ ; foundation grant//Jenny ja Antti Wihurin Rahasto/ ; },
mesh = {*Metformin/pharmacology ; Humans ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Mitophagy/drug effects ; *Mitochondria/drug effects/metabolism ; *Inflammation/pathology/drug therapy ; *Reactive Oxygen Species/metabolism ; Cell Line ; Antimycin A/pharmacology ; Autophagy/drug effects ; Cell Survival/drug effects ; Macular Degeneration/pathology/drug therapy/metabolism ; },
abstract = {Mitochondrial malfunction, excessive production of reactive oxygen species (ROS), deficient autophagy/mitophagy, and chronic inflammation are hallmarks of age-related macular degeneration (AMD). Metformin has been shown to activate mitophagy, alleviate inflammation, and lower the odds of developing AMD. Here, we explored the ability of metformin to activate mitophagy and alleviate inflammation in retinal pigment epithelium (RPE) cells. Human ARPE-19 cells were pre-treated with metformin for 1 h prior to exposure to antimycin A (10 µM), which induced mitochondrial damage. Cell viability, ROS production, and inflammatory cytokine production were measured, while autophagy/mitophagy proteins were studied using Western blotting and immunocytochemistry. Metformin pre-treatment reduced the levels of proinflammatory cytokines IL-6 and IL-8 to 42% and 65% compared to ARPE-19 cells exposed to antimycin A alone. Metformin reduced the accumulation of the autophagy substrate SQSTM1/p62 (43.9%) and the levels of LC3 I and II (51.6% and 48.6%, respectively) after antimycin A exposure. Metformin also increased the colocalization of LC3 with TOM20 1.5-fold, suggesting active mitophagy. Antimycin A exposure increased the production of mitochondrial ROS (226%), which was reduced by the metformin pre-treatment (84.5%). Collectively, metformin showed anti-inflammatory and antioxidative potential with mitophagy induction in human RPE cells suffering from mitochondrial damage.},
}
@article {pmid39272986,
year = {2024},
author = {Prud'homme, GJ and Wang, Q},
title = {Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging.},
journal = {Cells},
volume = {13},
number = {17},
pages = {},
pmid = {39272986},
issn = {2073-4409},
support = {2-SRA-2018-497-A-B//Juvenile Diabetes Research Foundation/ ; 2-SRA-2015-64-Q-R//Juvenile Diabetes Research Foundation/ ; OG-3-13-4066//Diabetes Canada/ ; 81570518, 81630020, 82370814//National Science Foundation of China/ ; N/A//St. Michael's Hospital Foundation and Keenan Research Centre for Biomedical Science, Toronto/ ; },
mesh = {Animals ; Humans ; *Aging/metabolism/pathology ; Anti-Inflammatory Agents/metabolism/therapeutic use ; Fibroblast Growth Factor-23/metabolism ; *Glucuronidase/metabolism ; Inflammation/metabolism/pathology ; *Klotho Proteins/metabolism ; },
abstract = {The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It is produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia and other anomalies. Importantly, it is associated with chronic pathologies (often age-related) that have an inflammatory component. This includes atherosclerosis, diabetes and Alzheimer's disease. Its mode of action in these diseases is not well understood, but it inhibits or regulates multiple major pathways. Klotho has a membrane form and a soluble form (s-Klotho). Cytosolic Klotho is postulated but not well characterized. s-Klotho has endocrine properties that are incompletely elucidated. It binds to the FGF receptor 1c (FGFR1c) that is widely expressed (including endothelial cells). It also attaches to soluble FGF23, and FGF23/Klotho binds to FGFRs. Thus, s-Klotho might be a roaming FGF23 coreceptor, but it has other functions. Notably, Klotho (cell-bound or soluble) counteracts inflammation and appears to mitigate related aging (inflammaging). It inhibits NF-κB and the NLRP3 inflammasome. This inflammasome requires priming by NF-κB and produces active IL-1β, membrane pores and cell death (pyroptosis). In accord, Klotho countered inflammation and cell injury induced by toxins, damage-associated molecular patterns (DAMPs), cytokines, and reactive oxygen species (ROS). s-Klotho also blocks the TGF-β receptor and Wnt ligands, which lessens fibrotic disease. Low Klotho is associated with loss of muscle mass (sarcopenia), as occurs in aging and chronic diseases. s-Klotho counters the inhibitory effects of myostatin and TGF-β on muscle, reduces inflammation, and improves muscle repair following injury. The inhibition of TGF-β and other factors may also be protective in diabetic retinopathy and age-related macular degeneration (AMD). This review examines Klotho functions especially as related to inflammation and potential applications.},
}
@article {pmid39271642,
year = {2024},
author = {Borrelli, E and Coco, G and Pellegrini, M and Mura, M and Ciarmatori, N and Scorcia, V and Carnevali, A and Lucisano, A and Borselli, M and Rossi, C and Reibaldi, M and Ricardi, F and Vagge, A and Nicolò, M and Forte, P and Cartabellotta, A and Hasanreisoğlu, M and Kesim, C and Demirel, S and Yanık, &#xd6; and Bernabei, F and Rothschild, PR and Farrant, S and Giannaccare, G},
title = {Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {11},
pages = {2855-2868},
pmid = {39271642},
issn = {2193-8245},
abstract = {INTRODUCTION: Photobiomodulation (PBM) has become a promising approach for slowing the progression of early and intermediate dry age-related macular degeneration (dAMD) to advanced AMD. This technique uses light to penetrate tissues and activate molecules that influence biochemical reactions and cellular metabolism. This preliminary analysis is aimed at assessing the safety, tolerability, and short-term effectiveness of the EYE-LIGHT[®]PBM treatment device in patients with dAMD.<br><br>METHODS: The EYE-LIGHT[&#xae;] device employs two wavelengths, 590&#xa0;nm (yellow) and 630&#xa0;nm (red), in both continuous and pulsed modes. Patients over 50&#xa0;years of age with a diagnosis of dAMD in any AREDS (Age-Related Eye Disease Study) category were randomly assigned to either the treatment group or the sham group. The treatment plan consisted of an initial cycle of two sessions per week for 4&#xa0;weeks. Safety, tolerability, and compliance outcomes, along with functional and anatomical outcomes, were assessed at the end of the fourth month.<br><br>RESULTS: This preliminary analysis included data from 76 patients (152 eyes). All patients were fully compliant with treatment sessions, and only one fifth of patients treated with PBM reported mild ocular adverse events, highlighting exceptional results in terms of tolerability and adherence. Changes in best-corrected visual acuity (BCVA) from baseline to month 4 differed significantly between the sham and PBM-treated groups, favoring the latter, with a higher proportion achieving a gain of five or more letters post-treatment (8.9% vs. 20.3%, respectively; p&#x2009;=&#x2009;0.043). No significant differences in central subfield thickness (CST) were observed between the two groups over the 4-month period. The study also found a statistically significant disparity in mean drusen volume changes from baseline to month 4 between the groups in favor of patients treated with PBM (p&#x2009;=&#x2009;0.013).<br><br>CONCLUSION: These preliminary results indicate that PBM treatment using the EYE-LIGHT[&#xae;] system is safe and well tolerated among patients with dAMD. Furthermore, both functional and anatomical data support the treatment's short-term efficacy.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06046118.},
}
@article {pmid39269368,
year = {2024},
author = {Yang, Y and Zhang, S and Su, S and Yang, X and Chen, J and Sang, A},
title = {The Effects of STRA6 Regulation of the Circadian Rhythm on Choroidal Neovascularization.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {11},
pages = {21},
pmid = {39269368},
issn = {1552-5783},
mesh = {Animals ; Humans ; Male ; Mice ; Blotting, Western ; Cell Proliferation/physiology ; *Choroidal Neovascularization/metabolism/genetics/physiopathology ; *Circadian Rhythm/physiology ; *Disease Models, Animal ; Gene Expression Regulation/physiology ; Membrane Proteins/genetics/metabolism ; *Mice, Inbred C57BL ; Retinal Pigment Epithelium/metabolism/pathology ; Vascular Endothelial Growth Factor A/metabolism/genetics ; },
abstract = {PURPOSE: This study aims to investigate the relationship among STRA6, circadian rhythm, and choroidal neovascularization (CNV) formation, as well as the regulatory mechanism of STRA6 in CNV under circadian rhythm disturbances.<br><br>METHODS: C57BL/6J male mice (aged 6 weeks) were randomly divided into control and jet lag groups (using a time shift method every 4&#xa0;days to disrupt the molecular clock's capacity to synchronize with a stable rhythm). A laser-induced CNV model was established in both the control and the jet lag group after 2 weeks of jet lag. The size of CNV lesions and vascular leakage were detected by morphological and imaging examination on the seventh day post laser. STRA6 was screened by full transcriptome sequencing. Bioinformatics analysis was conducted to assess the variation and association of STRA6 in the GSE29801 dataset. The effects of STRA6 were evaluated both in vivo and in vitro. The pathway mechanism was further elucidated and confirmed through immunofluorescence of paraffin sections and Western blotting.<br><br>RESULTS: The disturbance of circadian rhythm promotes the formation of CNV. Patients with age-related macular degeneration (AMD) exhibited higher levels of STRA6 expression compared to the control group, and STRA6 was enriched in pathways related to angiogenesis. In addition, CLOCK and BMAL1, which are initiators that drive the circadian cycle, had regulatory effects on STRA6. Knocking down STRA6 reversed the promotion of CNV formation caused by circadian rhythm disturbance in vivo, and it also affected the proliferation, migration, and VEGF secretion of RPE cells without circadian rhythm in vitro, as well as impacting endothelial cells. Through activation of the JAK2/STAT3/VEGFA signaling pathway in unsynchronized RPE cells, STRA6 promotes CNV formation.<br><br>CONCLUSIONS: This study suggests that STRA6 reduces CNV production by inhibiting JAK2/STAT3 phosphorylation after circadian rhythm disturbance. The results suggest that STRA6 may be a new direction for the treatment of AMD.},
}
@article {pmid39268877,
year = {2025},
author = {Tsou, SC and Chuang, CJ and Hsu, CL and Chen, TC and Yeh, JH and Wang, M and Wang, I and Chang, YY and Lin, HW},
title = {The Novel Application of EUK-134 in Retinal Degeneration: Preventing Mitochondrial Oxidative Stress-Triggered Retinal Pigment Epithelial Cell Apoptosis by Suppressing MAPK/p53 Signaling Pathway.},
journal = {Environmental toxicology},
volume = {40},
number = {1},
pages = {88-100},
doi = {10.1002/tox.24416},
pmid = {39268877},
issn = {1522-7278},
support = {MOST-109-2320-B-468-004-MY3//Ministry of Science and Technology/ ; MOST 111-2320-B-040 -006 -MY3//Ministry of Science and Technology/ ; MOST-112-2320-B-468-002-MY3//Ministry of Science and Technology/ ; },
mesh = {*Oxidative Stress/drug effects ; Animals ; *Apoptosis/drug effects ; *Retinal Pigment Epithelium/drug effects/pathology ; *Salicylates/pharmacology ; *Iodates/toxicity ; *Mitochondria/drug effects ; *Organometallic Compounds/pharmacology ; Humans ; Cell Line ; *Mice, Inbred BALB C ; Signal Transduction/drug effects ; Tumor Suppressor Protein p53/metabolism ; Retinal Degeneration/prevention &amp; control/pathology/drug therapy ; MAP Kinase Signaling System/drug effects ; Antioxidants/pharmacology ; Mice ; Male ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of blindness, is characterized by mitochondrial dysfunction of retinal pigment epithelium (RPE) cells. EUK-134 is a mimetic of SOD2 and catalase, widely used for its antioxidant properties in models of light-induced damage or oxidative stress. However, its effects on the retina are not yet clear. Here, we investigated the capability of EUK-134 in averting AMD using sodium iodate (NaIO3)-induced Balb/c mouse and ARPE-19 cells (adult RPE cell line). In vivo, EUK-134 effectively antagonized NaIO3-induced retinal deformation and prevented outer and inner nuclear layer thinning. In addition, it was found that the EUK-134-treated group significantly down-regulated the expression of cleaved caspase-3 compared with the group treated with NaIO3 alone. Our results found that EUK-134 notably improved cell viability by preventing mitochondrial ROS accumulation-induced membrane potential depolarization-mediated apoptosis in NaIO3-inducted ARPE-19 cells. Furthermore, we found that EUK-134 could inhibit p-ERK, p-p38, p-JNK, p-p53, Bax, cleaved caspase-9, cleaved caspase-3, and cleaved PARP by increasing Bcl-2 protein expression. Additionally, we employed MAPK pathway inhibitors by SB203580 (a p38 inhibitor), U0126 (an ERK inhibitor), and SP600125 (a JNK inhibitor) to corroborate the aforementioned observation. The results support that EUK-134 may effectively prevent mitochondrial oxidative stress-mediated retinal apoptosis in NaIO3-induced retinopathy.},
}
@article {pmid39268278,
year = {2024},
author = {Radhakrishnan, O and Agrawal, T and Giri, N and Gandhi, S and Goyal, K},
title = {Factors Affecting Compliance and Visual Outcomes in Patients Receiving Intravitreal Bevacizumab Injections.},
journal = {Cureus},
volume = {16},
number = {8},
pages = {e66760},
pmid = {39268278},
issn = {2168-8184},
abstract = {Background Vascular endothelial growth factor (VEGF) is a powerful mitogen for endothelial cells that promotes migration, proliferation, and tube formation necessary for the angiogenic development of new blood vessels. When VEGF increases significantly, it causes pathological angiogenesis and increased vascular permeability in eye conditions such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). These disorders have become important global sources of morbidity and have a substantial financial impact not only on the medical community but also on the patients. Therefore, this study aims to determine the success rates of intravitreal bevacizumab therapy and the visual outcomes which may be increased by determining the factors affecting patient compliance and raising awareness about DR, neovascular AMD, and RVO among patients and studying the factors responsible for non-compliance to treatment. Methodology This experimental pre-post study was conducted in the ophthalmology department at a tertiary care hospital and research center in western Maharashtra from September 2022 to June 2024. A total of 150 eyes of 150 patients who were diagnosed cases of DR, neovascular AMD, and non-ischemic RVO were included in the study. Written informed consent was obtained from each patient. Data were entered in Microsoft Excel (Microsoft Corp., Redmond, WA, USA) and statistical analysis was done using SPSS 27.0 software (IBM Corp., Armonk, NY, USA). The chi-square test was employed to check the association between categorical variables. Pearson's correlation test was used, and p-values <0.05 were considered significant. Results The compliance rate in our study was 79.3% (113 individuals). In our study, 58% (87 individuals) were male while 42% (63 individuals) were females. Most patients were from urban areas 74.7% (112 individuals). Among the study participants, DR patients constituted 48.6% (73 individuals), while neovascular AMD and RVO were seen in 32% (48 individuals) and 19.4% (29 individuals), with 62% (93 individuals) being diabetic and 64.7% (97 individuals) being hypertensive. In our study, 92% (138 individuals) were willing to take treatment, with 88.7% (133 individuals) worried about their visual outcomes and 66% (99 individuals) afraid of getting injected. Appointments posed a financial burden to 30.7% (46 individuals) of patients, with 55.3% (83 individuals) having transportation issues. Overall, 18.7% (28 individuals) of patients had missed appointments between 14 and 90 days while 30.7% (46 individuals) had missed their appointments by 90 and 365 days. Younger patients with a shorter duration of diabetes had higher compliance rates. Post-injection, there was an overall significant improvement in vision as well as a reduction in the central subfield macular thickness, volume cube, and thickness average cube. Conclusions In the present study, four-fifths of the patients were compliant with treatment, and visual improvement was significant. In addition, there was a significant reduction in the macular thickness after the treatment. One of the factors for non-compliance included in our study was the need for follow-up. Younger patients and those with a shorter duration of diabetes had significantly higher compliance. We recommend further studies should be conducted to compare the effectiveness with the control group in randomized control trials.},
}
@article {pmid39264086,
year = {2024},
author = {Scott Sills, E and Harrity, C and Chu, HI and Wang, JW and Wood, SH and Tan, SL},
title = {First Application of Whole Genome Sequencing in Myelinated Retinal Nerve Fibers (MRNF).},
journal = {Physiological research},
volume = {73},
number = {4},
pages = {665-670},
pmid = {39264086},
issn = {1802-9973},
mesh = {Humans ; Female ; Young Adult ; *Whole Genome Sequencing ; *Nerve Fibers, Myelinated/pathology ; Retina/pathology ; Genetic Predisposition to Disease ; },
abstract = {Genetic features are currently unknown in myelinated retinal nerve fibers (MRNF). For a 20-year-old asymptomatic female with unilateral MRNF, we performed whole genome sequencing (WGS) by standard workflow protocol to produce contiguous long-read sequences with Illumina DNA PCR-Free Prep. After tagmentation, libraries were sequenced on separate runs via NovaSeq 6000 platform at 2 x 150bp read length. Gene variants included rs2248799, rs2672589, rs7555070, rs247616_T and rs2043085_C all associated with an increased macular degeneration risk, and seven novel variants of uncertain significance. For optic disc enlargement, variants rs9988687_A, rs11079419_T, rs6787363 and rs10862708_A suggested an increased risk for this condition. In contrast, modeling revealed retinal detachment risk was reduced by variants identified at rs9651980_T, rs4373767_T, and rs7940691_T which were among five other previously unreported variants. WGS data placed proband at the 66th and 64th percentiles for disc anomaly and retinal detachment risk, respectively. Additionally, risk determined from 16 loci associated with age-related macular degeneration found the patient to be at the 18th percentile for this diagnosis (i.e., below average genetic predisposition). Fundoscopic findings showed mean RNFL thickness was lower with MRNF (77 OS vs. 96?m OD) and RNFL symmetry was impaired (43 %) but stable between 2020 and 2023. Rim area and cup volume were also substantially different (2.33 OS vs. 1.34mm2 OD, and 0.001 OS vs. 0.151mm3 OD, respectively). As the first known evaluation of MRNF via WGS, these data reveal a mixed picture with variants associated with different risks for potentially related ocular pathologies. In addition, we identify multiple new variants of unknown significance. Factors affecting gene expression in MRNF require further study. Key words: Whole genome sequencing, Retina, Myelination, Anatomy, Gene variants.},
}
@article {pmid39263688,
year = {2024},
author = {Yu, MD and Bommakanti, N and Yonekawa, Y and Pulido, JS},
title = {Minocycline-induced retinal pigment epithelium hyperpigmentation masquerading as age-related macular degeneration: Case presentation and proposed mechanism.},
journal = {American journal of ophthalmology case reports},
volume = {36},
number = {},
pages = {102154},
pmid = {39263688},
issn = {2451-9936},
abstract = {PURPOSE: We describe the case of an 80-year-old man with bilateral minocycline-induced retinal pigment epithelium (RPE) hyperpigmentation, which initially masqueraded as AMD. Secondarily, using multimodal imaging features, we propose a mechanism for the development of minocycline-induced RPE hyperpigmentation.<br><br>OBSERVATIONS: The patient was referred with concern for AMD given the presence of macular drusenoid deposits on optical coherence tomography. However, funduscopic evaluation showed dense granular parafoveal hyperpigmentation, with a diffuse slate-colored hyperpigmentation throughout the peripheral fundus. Short-wavelength fundus autofluorescence of the macula disclosed no irregularities (as would be expected with drusen) while on near-infrared reflectance (NIR) imaging, numerous hyperreflective foci were noted corresponding to the hyperpigmented granules observed clinically (as would instead be seen with melanin deposits). Clinical examination was notable for blue-gray hyperpigmentation of the lower and upper extremities, as well as of the face, periorbital skin, and sclera. Upon further questioning, the patient disclosed daily oral minocycline use for 15 years for acne rosacea, confirming a diagnosis of minocycline-induced hyperpigmentation of the RPE.<br><br>CONCLUSIONS: Multimodal imaging can be useful for differentiating minocycline-induced RPE hyperpigmentation from similar masquerade entities. Timely diagnosis can prevent progressive vision loss.},
}
@article {pmid39261653,
year = {2024},
author = {Sun, H and Li, L and Bu, F and Xin, X and Yan, J and Huang, T},
title = {Two-year efficacy and safety of different anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: a network meta-analysis of randomized controlled trials.},
journal = {Eye (London, England)},
volume = {38},
number = {18},
pages = {3473-3480},
pmid = {39261653},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/adverse effects ; *Randomized Controlled Trials as Topic ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/physiopathology ; Treatment Outcome ; Ranibizumab/therapeutic use/administration &amp; dosage/adverse effects ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/antagonists &amp; inhibitors ; Bevacizumab/therapeutic use/adverse effects ; Recombinant Fusion Proteins/therapeutic use/adverse effects ; },
abstract = {OBJECTIVES: To compare the 2-year efficacy and safety of various anti-vascular endothelial growth factor (VEGF) regimens for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A comprehensive search was performed on multiple electronic databases up to April 2023 and updated in June 2024, to identify relevant randomized controlled trials (RCTs). Key outcomes included the proportion of patients achieving a vision gain of &#x2265;15 letters and maintaining stable vision (loss of <15 letters) in best-corrected visual acuity (BCVA), changes in mean BCVA from baseline, serious ocular adverse events (SAEs), adverse events leading to treatment discontinuation and any cause of death at 2 years.<br><br>RESULTS: Nineteen trials with 12,654 patients and 25 treatment regimens were analyzed in the study. All anti-VEGF regimens showed superior efficacy compared to sham therapy. Specifically, faricimab 6&#x2009;mg (4+up to Q16W) and ranibizumab 0.5&#x2009;mg (2-week T&amp;E) displayed top-level effect in vision gain. Bevacizumab 1.25&#x2009;mg (2-week T&amp;E) and aflibercept 2&#x2009;mg (2-week T&amp;E) demonstrated the most stable vision outcomes. Bevacizumab 1.25&#x2009;mg (2-week T&amp;E) and ranibizumab 0.5&#x2009;mg (2-week T&amp;E) exhibited the most pronounced mean BCVA improvement. Compared to sham therapy, the risk of SAEs was significantly higher for brolucizumab 6&#x2009;mg (3&#x2009;+&#x2009;Q12W/ Q8W) (RR&#x2009;=&#x2009;6.04, 95% CI: 1.30-28.02) and PDS 100&#x2009;mg/ml (Q24W) (RR&#x2009;=&#x2009;10.95, 95% CI: 2.14-56.02), but not for other anti-VEGF regimens.<br><br>CONCLUSIONS: Ranibizumab 0.5&#x2009;mg (2-week T&amp;E) emerges as a potentially optimal regimen for nAMD over a 2-year period. Future studies need to consider the impact of baseline characteristics on treatment outcomes.},
}
@article {pmid39260755,
year = {2024},
author = {Sørensen, TL},
title = {Age-related macular degeneration (AMD) is a detrimental eye disease, and the most common cause of visual loss in many countries around the world.},
journal = {Pharmacological research},
volume = {208},
number = {},
pages = {107402},
doi = {10.1016/j.phrs.2024.107402},
pmid = {39260755},
issn = {1096-1186},
mesh = {Humans ; *Macular Degeneration/epidemiology ; Animals ; Vision Disorders/etiology ; },
}
@article {pmid39260410,
year = {2025},
author = {Desideri, LF and Zinkernagel, M and Anguita, R},
title = {Artificial Intelligence in Neovascular Age-Related Macular Degeneration.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {242},
number = {9},
pages = {894-900},
doi = {10.1055/a-2413-6782},
pmid = {39260410},
issn = {1439-3999},
mesh = {Humans ; *Artificial Intelligence ; Deep Learning ; *Macular Degeneration/diagnosis/therapy ; Disease Progression ; *Wet Macular Degeneration/diagnosis/therapy ; },
abstract = {The integration of artificial intelligence (AI) into the management of neovascular age-related macular degeneration (nAMD) presents a transformative opportunity in ophthalmology. In particular, deep learning (DL) models have shown remarkable accuracy in detecting nAMD, predicting disease progression and forecasting treatment outcomes. This review provides a comprehensive analysis of current AI applications in nAMD, focusing on the performance of these models in diagnostic tasks, including classification, object detection, and segmentation, as well as their potential to outperform human experts in specific domains. The review further explores how AI-driven predictive models can personalize treatment strategies by forecasting individual responses to therapies, such as anti-VEGF, and predicting the conversion from intermediate AMD to nAMD. Despite these promising developments, significant challenges remain, including the need for extensive datasets, seamless integration into clinical workflows, and ensuring the generalizability of AI predictions across diverse populations. Continued validation and the development of user-friendly AI tools are crucial for broader adoption and improved patient outcomes. In conclusion, identifying effective pathways to overcome these challenges will be essential as the field continues to evolve.},
}
@article {pmid39260309,
year = {2024},
author = {Zhu, M and Yu, J},
title = {Salidroside alleviates ferroptosis in FAC-induced Age-related macular degeneration models by activating Nrf2/SLC7A11/GPX4 axis.},
journal = {International immunopharmacology},
volume = {142},
number = {Pt A},
pages = {113041},
doi = {10.1016/j.intimp.2024.113041},
pmid = {39260309},
issn = {1878-1705},
mesh = {Animals ; *Glucosides/pharmacology/therapeutic use ; *Ferroptosis/drug effects ; *Phenols/therapeutic use/pharmacology ; *NF-E2-Related Factor 2/metabolism ; *Macular Degeneration/drug therapy/pathology/metabolism ; Humans ; *Mice, Inbred C57BL ; Cell Line ; Mice ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism/genetics ; *Disease Models, Animal ; Quaternary Ammonium Compounds/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Male ; Rhodiola/chemistry ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Reactive Oxygen Species/metabolism ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a significant contributor to irreversible impairment in visual capability, particularly in its non-neovascular (dry) form. Ferroptosis, an emerging form of programmed necrosis, involves generating lipid peroxidation (LOS) through free iron and reactive oxygen species (ROS). Salidroside, a glycoside from Rhodiola rosea, known for anti-inflammatory and antioxidant properties. The research aim was exploring whether ferroptosis exists in dry AMD pathogenesis and elucidate salidroside's protective mechanisms against ferroptosis in AMD murine models and ARPE-19 cells.<br><br>METHODS: ARPE-19 cells were treated with varying concentrations of ferrous ammonium citrate (FAC) and salidroside. In an in vivo model, C57BL/6 mice were administered intraperitoneal injections of salidroside for 7 consecutive days, followed by an intravitreal injection (IVT) of FAC. After 7&#xa0;days, the eyeballs were harvested for subsequent analyses. Ferroptosis markers were assessed using western blotting, immunofluorescence staining, and flow cytometry. To further elucidate the modulatory role of Nrf2 in ferroptosis, ARPE-19 cells were transfected with si-Nrf2.<br><br>RESULTS: In vitro, FAC-treated ARPE-19 cells exhibited reduced viability, decreased mitochondrial membrane potential (MMP), and accumulation of iron and lipid peroxidation (LOS) products. In vivo, FAC administration by IVT led to outer nuclear layer thinning and compromised tight junctions in RPE cells. The GPX4, Nrf2, and SLC7A11 expressions were downregulated both in vitro and in vivo. Salidroside upregulated Nrf2 and ameliorated these outcomes, but its effects were attenuated in ARPE-19 cells transfected with si-Nrf2.<br><br>CONCLUSION: Our study establishes that FAC induces RPE cell ferroptosis within dry AMD, and salidroside exerts therapeutic effects by triggering Nrf2/SLC7A11/GPX4 signaling axis.},
}
@article {pmid39260060,
year = {2024},
author = {Gáll, T and Pethő, D and Erdélyi, K and Egri, V and Balla, JG and Nagy, A and Nagy, A and Póliska, S and Gram, M and Gábriel, R and Nagy, P and Balla, J and Balla, G},
title = {Heme: A link between hemorrhage and retinopathy of prematurity progression.},
journal = {Redox biology},
volume = {76},
number = {},
pages = {103316},
pmid = {39260060},
issn = {2213-2317},
mesh = {Humans ; *Retinopathy of Prematurity/metabolism/pathology ; *Heme/metabolism ; *Vascular Endothelial Growth Factor A/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; Infant, Newborn ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Cell Line ; Male ; Phosphatidylinositol 3-Kinases/metabolism ; Female ; Reactive Oxygen Species/metabolism ; Disease Progression ; Proto-Oncogene Proteins c-akt/metabolism ; Retrospective Studies ; },
abstract = {Neovascularization is implicated in the pathology of retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD), which are the leading causes of blindness worldwide. In our work, we analyzed how heme released during hemorrhage affects hypoxic response and neovascularization. Our retrospective clinical analysis demonstrated, that hemorrhage was associated with more severe retinal neovascularization in ROP patients. Our heme-stimulated human retinal pigment epithelial (ARPE-19) cell studies demonstrated increased expression of positive regulators of angiogenesis, including vascular endothelial growth factor-A (VEGFA), a key player of ROP, DR and AMD, and highlighted the activation of the PI3K/AKT/mTOR/VEGFA pathway involved in angiogenesis in response to heme. Furthermore, heme decreased oxidative phosphorylation in the mitochondria, augmented glycolysis, facilitated HIF-1α nuclear translocation, and increased VEGFA/GLUT1/PDK1 expression suggesting HIF-1α-driven hypoxic response in ARPE-19 cells without effecting the metabolism of reactive oxygen species. Inhibitors of HIF-1α, PI3K and suppression of mTOR pathway by clinically promising drug, rapamycin, mitigated heme-provoked cellular response. Our data proved that oxidatively modified forms of hemoglobin can be sources of heme to induce VEGFA during retinal hemorrhage. We propose that hemorrhage is involved in the pathology of ROP, DR, and AMD.},
}
@article {pmid39259701,
year = {2024},
author = {Pucker, AD and Derthick, N and Scott, L},
title = {Running the enrollment numbers on ophthalmic clinical trials in the United States.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {101},
number = {8},
pages = {523-529},
doi = {10.1097/OPX.0000000000002174},
pmid = {39259701},
issn = {1538-9235},
mesh = {Humans ; United States ; *Clinical Trials as Topic ; *Ophthalmology ; *Eye Diseases/drug therapy ; United States Food and Drug Administration ; Patient Selection ; },
abstract = {SIGNIFICANCE: This is one of the first reports to summarize the enrollment metrics for ophthalmology trials completed in the United States (US).<br><br>PURPOSE: This study aimed to describe US ophthalmology clinical trial enrollment metrics to facilitate planning and budgeting of US Food and Drug Administration-regulated ophthalmological drugs trials.<br><br>METHODS: A GlobalData PLC search was conducted on or before February 27, 2024, to evaluate the clinical trial landscape for completed ophthalmology clinical trials conducted in the US. The primary search contained only the term "ophthalmology," which was restricted to trials that were completed and were conducted within the US. Trials were classified as multicenter when trials included three sites or more, and when the enrollment search resulted in &#x2265;30 multicenter trials for an individual indication, enrollment data were further broken down by Food and Drug Administration trial phase.<br><br>RESULT: The search yielded 2229 trials, which analyzed 980 different drugs produced by 854 different sponsors. The most common indications evaluated in US trials were macular degeneration, glaucoma, macular edema, allergies, and keratoconjunctivitis. Multicenter trials by indication had an overall median enrollment period range of 4.8 to 35.1 months; number of subjects enrollment, range of 36 to 518 subjects; number of sites utilized, range of 4 to 74 sites; and enrollment rate, range of 0.11 to 4.04 subjects/sites per month. There were 17 indications with &#x2265;30 multicenter trials, which allowed for enrollment metric calculation by trial phase.<br><br>CONCLUSIONS: This study provides sponsors with an understanding of the number of subjects and sites needed to complete a trial while also setting realistic enrollment timelines. Although this work represents the US market, more work is needed to better understand other countries given that country-specific guidelines and subject beliefs may impact enrollment metrics.},
}
@article {pmid39259599,
year = {2024},
author = {Enzendorfer, ML and Schmidt-Erfurth, U},
title = {Artificial intelligence for geographic atrophy: pearls and pitfalls.},
journal = {Current opinion in ophthalmology},
volume = {35},
number = {6},
pages = {455-462},
pmid = {39259599},
issn = {1531-7021},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Artificial Intelligence ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Algorithms ; },
abstract = {PURPOSE OF REVIEW: This review aims to address the recent advances of artificial intelligence (AI) in the context of clinical management of geographic atrophy (GA), a vision-impairing late-stage manifestation of age-related macular degeneration (AMD).<br><br>RECENT FINDINGS: Recent literature shows substantial advancements in the development of AI systems to segment GA lesions on multimodal retinal images, including color fundus photography (CFP), fundus autofluorescence (FAF) and optical coherence tomography (OCT), providing innovative solutions to screening and early diagnosis. Especially, the high resolution and 3D-nature of OCT has provided an optimal source of data for the training and validation of novel algorithms. The use of AI to measure progression in the context of newly approved GA therapies, has shown that AI methods may soon be indispensable for patient management. To date, while many AI models have been reported on, their implementation in the real-world has only just started. The aim is to make the benefits of AI-based personalized treatment accessible and far-reaching.<br><br>SUMMARY: The most recent advances (pearls) and challenges (pitfalls) associated with AI methods and their clinical implementation in the context of GA will be discussed.},
}
@article {pmid39259423,
year = {2025},
author = {Babighian, S and Zanella, MS and Gattazzo, I and Galan, A and Gagliano, C and D'Esposito, F and Zeppieri, M},
title = {Atrophic Macular Degeneration and Stem Cell Therapy: A Clinical Review.},
journal = {Advances in experimental medicine and biology},
volume = {1474},
number = {},
pages = {105-118},
pmid = {39259423},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/therapy/pathology ; *Stem Cell Transplantation/methods ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence ; Clinical Trials as Topic ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of visual loss in older patients. No effective drug is available for this pathology, but studies about therapy with stem cells replacing the damaged retinal cells with retinal pigment epithelium (RPE) were described. The documentation of AMD progression and the response to stem cell therapy have been performed by optical coherence tomography, microperimetry, and other diagnostic technologies.This chapter reports a clinical review of the most important clinical trials and protocols regarding the use of stem cells in AMD.},
}
@article {pmid39257593,
year = {2024},
author = {Thapa, R and Ruit, S and Poudel, MP and Neupane, P and Banjara, P and Duwal, S and Gurung, E and Tabin, G},
title = {Population Prevalence, Pattern and Associated Factors for Retinal Diseases at High Altitude in Nepal.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {2555-2565},
pmid = {39257593},
issn = {1177-5467},
abstract = {BACKGROUND: Retinal diseases are common at high altitudes due to a cascade of changes caused by hypoxia. The aim of this study is to assess the population prevalence, pattern and associated factors of retinal disorders at high altitude in Nepal.<br><br>METHODOLOGY: A cross-sectional study was conducted at three selected high-altitude districts (over 2500 meters) of Nepal. Subjects were at least 40 years old, and the target sample size was 309. A detailed history was taken. Visual acuity, blood sugar, blood pressure, and oxygen saturation were measured. Anterior and posterior ocular evaluations were conducted by retina specialists using slit lamp and indirect ophthalmoscopy.<br><br>RESULTS: A total of 338 participants were recruited, with nearly equal numbers from the three districts with mean age of 57.0 (S.D 11.1) years. Two-thirds (63.9%) were females; 38.2% were illiterate, and 46.7% were farmers. Average blood oxygen saturation was 87.2% (S.D 4.1%). Systemic hypertension and diabetes mellitus were found in 58% and 11%, respectively. Retinal diseases were found in 176 (52.5%), with bilateral involvement in 157 (46.9%). The major retinal diseases were hypertensive retinopathy (32.2%), high-altitude retinopathy (10.4%), age-related macular degeneration (AMD) (8.1%), branch vein occlusion (BRVO) (2.1%), and diabetic retinopathy (DR) (1.8%). The multivariate analysis showed significant association of retinal diseases with age and hypertension. Best corrected visual acuity better than 6/18 was present in 96.7%.<br><br>CONCLUSION: Over half of the study participants had retinal diseases, with hypertensive retinopathy, AMD, and high-altitude retinopathy as the most common retinal problems. A significant association of retinal diseases was found with ageing, and hypertension. Access to eye care services and control of systemic hypertension along with patient education should be emphasized among people living at high-altitude.},
}
@article {pmid39257094,
year = {2025},
author = {Bansal, M},
title = {Advances in retina genetics: Progress, potential, and challenges.},
journal = {Indian journal of ophthalmology},
volume = {73},
number = {Suppl 1},
pages = {S31-S36},
pmid = {39257094},
issn = {1998-3689},
mesh = {Humans ; *Retinal Diseases/genetics/therapy ; Retina ; Genetic Therapy/methods ; },
abstract = {The field of retinal genetics has seen remarkable advancements lately, reshaping our understanding of various retinal conditions, including age-related macular degeneration, diabetic retinopathy, and inherited retinal dystrophies. The purpose of this review is to provide an overview of the current status of genetics in the retina, covering the progress made, the expected future developments, and the challenges yet to be overcome. We highlight key advancements such as the advent of next-generation sequencing, which has exponentially enhanced the discovery of genetic mutations, thus also enabling personalized medicine/therapeutic approaches. Stem cells, gene augmentation, and gene-editing techniques such as CRISPR/Cas9 are discussed, in which we highlight ongoing research as well as their potential in the targeted treatment of retinal diseases. Despite these promising advancements, the field faces significant challenges, such as the complex interpretation of genetic data, ethical considerations, and the translational gap from bench to bedside. This review serves as a comprehensive guide not only to ophthalmologists but also to other healthcare professionals, scientists, and policymakers, providing insights into the rapidly evolving landscape of retinal genetics. It aims to stimulate further research and collaboration to surmount existing challenges and harness the full potential of genetic advancements for retinal health.},
}
@article {pmid39257072,
year = {2024},
author = {Fabozzi, L and Younis, S and Sen, S and López-Cuenca, I and Palmieri, F},
title = {Brolucizumab in patients with neovascular age-related macular degeneration: Real-life outcomes from a tertiary care eye hospital.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 5},
pages = {S752-S757},
pmid = {39257072},
issn = {1998-3689},
mesh = {Humans ; Male ; Female ; *Intravitreal Injections ; *Tomography, Optical Coherence/methods ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; *Fluorescein Angiography/methods ; Treatment Outcome ; Retrospective Studies ; Follow-Up Studies ; Tertiary Care Centers ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Fundus Oculi ; Middle Aged ; },
abstract = {PURPOSE: To report real-world clinical evidence of brolucizumab in treating neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This study included 37 eyes with nAMD treated with intravitreal injections of brolucizumab. The main outcomes were best corrected visual acuity (BCVA) changes, central retinal thickness (CRT), and serious ocular adverse events. Intraretinal fluid (IRF) and subretinal fluid (SRF), subretinal hyperreflective material (SHRM), pigment epithelial detachments (PEDs), hyperreflective foci, macular atrophy, and retinal pigment epithelial tears were evaluated.<br><br>RESULTS: The mean BCVA of all patients showed a post-treatment value of 0.47 &#xb1; 0.33 log of minimum angle of resolution (LogMAR), compared to a baseline measure of 0.50 &#xb1; 0.28 LogMAR (P = 0.372). For treatment-na&#xef;ve patients, a non-statistically significant improvement in BCVA was observed (P = 0.116). Both treatment-naive patients and the entire patient cohort exhibited a statistically significant improvement in the mean CRT after injections. Majority of patients exhibited improvements in optical coherence tomography findings, specifically in the resolution of IRF, SRF, SHRM, and PEDs. Four eyes experienced ocular adverse events in the form of intraocular inflammation.<br><br>CONCLUSION: Brolucizumab did not yield a substantial improvement in BCVA, but it exhibited efficacy in reducing CRT in the entire study population and treatment-naive patients with nAMD. Our study identified intraocular inflammation as a significant adverse event with brolucizumab. Thus, precise patient selection, education, and vigilant inflammation monitoring are crucial for patients undergoing this treatment.},
}
@article {pmid39256212,
year = {2024},
author = {Christoph, SEG and Boden, KT and Pütz, A and Januschowski, K and Siegel, R and Seitz, B and Szurman, P and Schulz, A},
title = {Epidemiology and phenomenology of the Charles Bonnet syndrome in low-vision patients.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {375},
pmid = {39256212},
issn = {1573-2630},
mesh = {Humans ; *Charles Bonnet Syndrome/epidemiology/complications ; Female ; Male ; Aged ; *Vision, Low/epidemiology ; Prevalence ; Middle Aged ; *Visual Acuity ; Aged, 80 and over ; Hallucinations/epidemiology/etiology ; Adult ; },
abstract = {BACKGROUND: The occurrence of visual hallucinations in visually impaired people without mental impairment is known as Charles Bonnet Syndrome (CBS). To date, the prevalence of CBS has been reported with high variance. The present study aims at evaluating the prevalence of CBS among low-vision patients.<br><br>METHODS: From March 2018 to February 2022, 194 patients with a visual acuity&#x2009;&#x2265;&#x2009;0.5&#xa0;logMAR approached the low vision section of the Eye Clinic Sulzbach. Of these, 50 patients were found eligible, agreed to participate in the study and were screened for CBS. The course of the disease, its phenomenology and characteristics, the circumstance of onset, the ability to manipulate and resolve the hallucinations, and the psychosocial aspects of CBS were investigated.<br><br>RESULTS: 26% of patients with low vision suffered from CBS. Women did not suffer from CBS significantly more often than men. Often, insight into the unreality of the images is not achieved immediately. Patterns or so-called "simple" hallucinations occurred just as frequently as other types of images such as people, body parts or faces. The most frequent images were animals. Visual hallucinations, lasting only for seconds in most cases, occurred more frequently during the day and in bright surroundings. All patients experienced the hallucinations exclusively with their eyes open. The hallucinations generally did not move with the eyes. Many sufferers did neither communicate about their hallucinations nor consult any physician.<br><br>CONCLUSIONS: CBS among low-vision patients is common. Its prevalence constitutes clinical relevance. Future management of CBS may benefit from encouraging patients to share their experiences and consult a physician.},
}
@article {pmid39255815,
year = {2024},
author = {Faatz, H and Lommatzsch, AP},
title = {[Age-related macular degeneration - Part 1: Pathophysiology, classification and diagnostic].},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2367-8346},
pmid = {39255815},
issn = {1439-3999},
abstract = {Age-related macular degeneration (AMD) continues to be the most common hereditary disease among older people in the western world. In addition to the clinical examination, multimodal imaging with fluorescein angiography, optical coherence tomography, fundus autofluorescence and fundus photography are crucial for the correct diagnosis and classification. This is particularly important with regard to risk assessment for the development of a late form of the disease. Since the introduction of intravitreal therapy against vascular endothelial growth factor (VEGF), the treatment options for neovascular AMD have increased significantly and the prognosis for patients in terms of maintaining their vision has improved. The hope is to develop stronger and longer-lasting drugs and also to obtain approval for drugs to treat geographic atrophy. It is therefore of great importance to be able to make a quick and correct diagnosis for patients. In this paper we want to present an overview of the pathophysiology, classification and diagnosis of AMD.},
}
@article {pmid39255420,
year = {2025},
author = {Savastano, A and D'Onofrio, NC and Francione, G and Sasso, P and Hu, L and Rizzo, S},
title = {SING-IMT Removal for Unsatisfied Patients: Step-by-Step Surgery for a Safe Explant.},
journal = {Retina (Philadelphia, Pa.)},
volume = {45},
number = {4},
pages = {798-800},
doi = {10.1097/IAE.0000000000004209},
pmid = {39255420},
issn = {1539-2864},
mesh = {Humans ; *Device Removal/methods ; Intraocular Pressure/physiology ; *Lens Implantation, Intraocular/methods ; *Lenses, Intraocular ; *Macular Degeneration/surgery ; Visual Acuity/physiology ; },
abstract = {PURPOSE: To report three cases of Smaller-Incision New-Generation Implantable Miniature Telescope (SING-IMG) explantation and three-piece acrylic intraocular lens (IOL) implantation in patients affected by late-stage dry age-related macular degeneration.<br><br>METHODS: This is a single-center cohort study. Three patients with stable dry age-related macular degeneration previously implanted with SING-IMT failed to adapt to the device requesting its explantation. Surgical procedures were performed under peribulbar anesthesia, with careful removal of the SING-IMT telescope through a sclerocorneal tunnel of 8 mm and implantation of a three-piece acrylic IOL. Patients underwent pre- and postoperative assessments, including visual acuity measurements, endothelial cell count, and intraocular pressure. Patients were followed postoperatively for at least 6 months, with particular attention to IOL stability and posterior capsule integrity.<br><br>RESULTS: Postoperative assessments demonstrated positive outcomes, revealing no IOL dislocation or posterior capsular opacification after 6 months. Endothelial cell count diminished. Best-corrected visual acuity returned to values before SING-IMT implantation.<br><br>CONCLUSION: In our small cohort, SING-IMT explantation appeared to be a safe option. Despite promising visual outcomes, some patients might not adapt to SING-IMT. Further studies are needed to evaluate criteria to predict telescope adaptation.},
}
@article {pmid39254670,
year = {2024},
author = {Mascia, KL},
title = {Genetic disease amongst the Plain community.},
journal = {Current opinion in pediatrics},
volume = {36},
number = {6},
pages = {599-604},
doi = {10.1097/MOP.0000000000001392},
pmid = {39254670},
issn = {1531-698X},
mesh = {Humans ; *Genetic Testing ; *Amish/genetics ; Genetic Diseases, Inborn/genetics/therapy ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Genetic Therapy/methods ; Telemedicine ; Child ; },
abstract = {PURPOSE OF REVIEW: The purpose of this review is to highlight recent genetic studies of the Amish and Mennonite (Plain) communities. For decades, the study of genetically isolated populations has improved our understanding and management of genetic diseases that affect all populations.<br><br>RECENT FINDINGS: Major themes of current genetic research of the Amish and Mennonites include new causative gene and new candidate gene discovery, phenotype expansion of previously identified genetic disease, and a target for AAV9-mediated gene therapy. Additionally, several genome-wide association studies (GWAS) examining complex traits such as dementia, cardiometabolic disease, and age-related macular degeneration have been conducted. Finally, clinically relevant studies of attitudes of the Plain community towards genetic testing and telemedicine, as well as reviews of and management suggestions for the Amish variants of propionic acidemia and APOB -associated familial hypercholesterolemia have been recently published.<br><br>SUMMARY: Recent genetic studies of the Plain community continue to highlight the value of studying isolated populations to propel genetic disease discovery and treatment. Additionally, population-specific polygenic risk scores are needed for underrepresented and minority populations, to avoid exacerbating disparities in medical genetics care. Finally, it is important for clinicians to develop management guidelines for variants common in this rapidly growing population, such as propionic acidemia.},
}
@article {pmid39254497,
year = {2025},
author = {Lisker-Cervantes, A and Gill, Z and Patnaik, JL and Gnanaraj, R and Lynch, AM and Palestine, AG and Mathias, M and Manoharan, N and Mandava, N and de Carlo Forest, TE},
title = {Association Between Systemic Levels of Vascular Endothelial Growth Factor and Optical Coherence Tomography Biomarkers in a Non-Neovascular Age-Related Macular Degeneration Cohort.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {56},
number = {1},
pages = {23-29},
doi = {10.3928/23258160-20240805-03},
pmid = {39254497},
issn = {2325-8179},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Vascular Endothelial Growth Factor A/blood ; Cross-Sectional Studies ; Male ; Female ; *Biomarkers/blood ; Aged ; Aged, 80 and over ; Retinal Pigment Epithelium/pathology ; Macular Degeneration/blood/diagnosis ; Middle Aged ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND AND OBJECTIVE: Investigate associations between systemic vascular endothelial growth factor (VEGF) and optical coherence tomography (OCT) biomarkers in eyes with complete retinal pigment epithelium and outer retina atrophy (cRORA) secondary to non-neovascular age-related macular degeneration.<br><br>PATIENTS AND METHODS: Cross-sectional study of patients with cRORA. OCT images and blood samples were collected at study enrollment. OCT images were evaluated for biomarkers. Systemic VEGF levels were measured using a standard multiplex assay.<br><br>RESULTS: Study included 187 eyes from 96 patients. Lower levels of systemic VEGF were significantly associated with retinal pseudocysts (RPs) and sub-retinal hyper-reflective material (SHRM), a median of 7.7 pg/mL and 6.1 pg/mL for patients with the imaging biomarkers compared to those without (10.3 pg/mL [P = 0.004] and 9.3 pg/mL [P = 0.02], respectively).<br><br>CONCLUSION: This novel study shows that lower systemic VEGF levels were associated with SHRM and RP, which was shown to correspond to an intermediate stage of the atrophic process in age-related macular degeneration. Systemic VEGF could be a useful biomarker and therapeutic target for eyes with cRORA. [Ophthalmic Surg Lasers Imaging Retina 2025;56:23-29.].},
}
@article {pmid39254389,
year = {2024},
author = {Kulikov, AN and Zhalimova, VR and Nekrash, NA and Kalinicheva, YA and Vasilyev, AS and Maltsev, DS},
title = {[Effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {4},
pages = {40-48},
doi = {10.17116/oftalma202414004140},
pmid = {39254389},
issn = {0042-465X},
mesh = {Humans ; Male ; Female ; *Visual Acuity ; Aged ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/adverse effects ; Treatment Outcome ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Tomography, Optical Coherence/methods ; Macular Degeneration/drug therapy/diagnosis/physiopathology ; Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; },
abstract = {PURPOSE: This study analyzes the effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration (nAMD) in real clinical practice.<br><br>MATERIAL AND METHODS: The study included patients with nAMD who received brolucizumab treatment and evaluated the changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume, as well as the number of injections and adverse events.<br><br>RESULT: The group of previously treated patients included 28 subjects (28 eyes) that were switched to brolucizumab with a loading phase. By 12 months, BCVA changed from 0.43&#xb1;0.29 to 0.33&#xb1;0.27 LogMAR (p=0.11), CRT decreased from 281.5&#xb1;58.2 to 239.9&#xb1;45.6 &#xb5;m (p=0.02). The group of previously untreated patients included 29 subjects (29 eyes). By 12 months, BCVA changed from 0.47&#xb1;0.32 to 0.40&#xb1;0.30 LogMAR (p=0.09), CRT decreased from 333.2&#xb1;77.3 to 226.2&#xb1;49.6 &#xb5;m (p<0.001). Patients received 6.3&#xb1;0.7 injections. In this group, baseline choroidal thickness showed a statistically significant correlation with final visual acuity (r=0.54; p<0.05) and CRT (r= -0.5; p<0.05). The group of previously treated patients switched without a loading phase included 18 patients (18 eyes). By 6 months, BCVA changed from 0.42&#xb1;0.2 to 0.37&#xb1;0.26 LogMAR (p=0.42). CRT remained stable at 285.6&#xb1;56.9 &#xb5;m (p=0.97). No adverse events related to intraocular inflammation were reported during the course of 385 injections.<br><br>CONCLUSION: Brolucizumab therapy helps achieve significant anatomical and functional improvements in real clinical practice both in patients switched from previous treatments and in treatment-na&#xef;ve patients. Greater baseline choroidal thickness may be associated with better anatomical and functional outcomes with brolucizumab treatment.},
}
@article {pmid39253597,
year = {2024},
author = {Liao, HJ and Yang, YP and Liu, YH and Tseng, HC and Huo, TI and Chiou, SH and Chang, CH},
title = {Harnessing the potential of mesenchymal stem cells-derived exosomes in degenerative diseases.},
journal = {Regenerative therapy},
volume = {26},
number = {},
pages = {599-610},
pmid = {39253597},
issn = {2352-3204},
abstract = {Mesenchymal stem cells (MSCs) have gained attention as a promising therapeutic approach in both preclinical and clinical osteoarthritis (OA) settings. Various joint cell types, such as chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and release extracellular vesicles (EVs), which subsequently influence the biological activities of recipient cells. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown the potential to modulate various physiological and pathological processes through the modulation of cellular differentiation, immune responses, and tissue repair. This review explores the roles and therapeutic potential of MSC-EVs in OA and rheumatoid arthritis, cardiovascular disease, age-related macular degeneration, Alzheimer's disease, and other degenerative diseases. Notably, we provide a comprehensive summary of exosome biogenesis, microRNA composition, mechanisms of intercellular transfer, and their evolving role in the highlight of exosome-based treatments in both preclinical and clinical avenues.},
}
@article {pmid39253548,
year = {2024},
author = {Mulyukov, Z and Keane, PA and Sahni, J and Liakopoulos, S and Hatz, K and Wei Ting, DS and Gallego-Pinazo, R and Aslam, T and Gemmy Cheung, CM and De Salvo, G and Semoun, O and Somfai, GM and Stahl, A and Lujan, BJ and Lorand, D},
title = {Artificial Intelligence-Based Disease Activity Monitoring to Personalized Neovascular Age-Related Macular Degeneration Treatment: A Feasibility Study.},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100565},
pmid = {39253548},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the performance of a disease activity (DA) model developed to detect DA in participants with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Post hoc analysis.<br><br>PARTICIPANTS: Patient dataset from the phase III HAWK and HARRIER (H&amp;H) studies.<br><br>METHODS: An artificial intelligence (AI)-based DA model was developed to generate a DA score based on measurements of OCT images and other parameters collected from H&amp;H study participants. Disease activity assessments were classified into 3 categories based on the extent of agreement between the DA model's scores and the H&amp;H investigators' decisions: agreement ("easy"), disagreement ("noisy"), and close to the decision boundary ("difficult"). Then, a panel of 10 international retina specialists ("panelists") reviewed a sample of DA assessments of these 3 categories that contributed to the training of the final DA model. A panelists' majority vote on the reviewed cases was used to evaluate the accuracy, sensitivity, and specificity of the DA model.<br><br>MAIN OUTCOME MEASURES: The DA model's performance in detecting DA compared with the DA assessments made by the investigators and panelists' majority vote.<br><br>RESULTS: A total of 4472 OCT DA assessments were used to develop the model; of these, panelists reviewed 425, categorized as "easy" (17.2%), "noisy" (20.5%), and "difficult" (62.4%). False-positive and false negative rates of the DA model's assessments decreased after changing the assessment in some cases reviewed by the panelists and retraining the DA model. Overall, the DA model achieved 80% accuracy. For "easy" cases, the DA model reached 96% accuracy and performed as well as the investigators (96% accuracy) and panelists (90% accuracy). For "noisy" cases, the DA model performed similarly to panelists and outperformed the investigators (84%, 86%, and 16% accuracies, respectively). The DA model also outperformed the investigators for "difficult" cases (74% and 53% accuracies, respectively) but underperformed the panelists (86% accuracy) owing to lower specificity. Subretinal and intraretinal fluids were the main clinical parameters driving the DA assessments made by the panelists.<br><br>CONCLUSIONS: These results demonstrate the potential of using an AI-based DA model to optimize treatment decisions in the clinical setting and in detecting and monitoring DA in patients with nAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39253240,
year = {2024},
author = {Gawęcki, M and Grzybowski, A},
title = {Neurosensory retina detachment combined with retinal pigment epithelium separation from the choroid in the course of dry macular degeneration - A case report.},
journal = {Heliyon},
volume = {10},
number = {16},
pages = {e36246},
pmid = {39253240},
issn = {2405-8440},
abstract = {of advanced diagnostic methods shed the light on the variable course of age-related macular degeneration (AMD). Despite establishing AMD classifications used in clinical practice, there are still forms of AMD that do not fit into these systems. The case report presents a rare evolution of non-neovascular form of AMD presenting at baseline as large soft drusen. Within the 5 years of observation one eye with such form of AMD transformed to retinal pigment epithelial detachment and subsequently simultaneous separation of the neurosensory retina and the choroid from the RPE. As a result, on the spectral domain optical coherence tomography scan, the case presented with lone line of the RPE neighbored by subretinal fluid from the inner side and choroidal excavation from the outside. Macular neovascularization was excluded at each timepoint of the follow-up. During 2.5 years of observation post the onset of RPE separation, the case remained stable with maintained visual acuity at 0.25 Snellen and lack of progression to wet form of AMD. Further observation is needed to fully assess the eye's potential for visual preservation in the long term.},
}
@article {pmid39251914,
year = {2024},
author = {Bai, J and Wang, Y and Li, Y and Liu, Y and Wang, S},
title = {Protective effect of ghrelin in oxidative stress-induced age-related macular degeneration in vitro and in vivo.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {30},
number = {1},
pages = {142},
pmid = {39251914},
issn = {1528-3658},
support = {R21008//Zhejiang Province's New Talent in the Medical/ ; },
mesh = {*Oxidative Stress/drug effects ; *Macular Degeneration/etiology/metabolism/drug therapy/prevention &amp; control ; Animals ; *Ghrelin/pharmacology/metabolism ; Humans ; Mice ; *Disease Models, Animal ; *Retinal Pigment Epithelium/metabolism/drug effects ; Cell Line ; *Hydrogen Peroxide ; *Apoptosis/drug effects ; Iodates ; Antioxidants/pharmacology ; Mice, Inbred C57BL ; Male ; },
abstract = {Oxidative damage to human retinal pigment epithelial (RPE) cells is the main cause of age-related macular degeneration (AMD), in our previous work, we showed that ghrelin has an antioxidative effect on human lens epithelium (HLE) cells, however, the studies of using ghrelin in treating the degenerative diseases of the retina have rarely been reported. In this article, we assessed the effect of ghrelin on preventing oxidative stress induced by hydrogen peroxide (H2O2) in ARPE-19 cells and its mechanism. We observed that pretreatment with ghrelin protected ARPE-19 cells from H2O2-induced cell oxidative injuries and apoptosis responses. Furthermore, an oxidative stress-induced mouse model of AMD was established via injection of sodium iodate (NaIO3) to tail veins, and treatment with ghrelin preserved retinal function, and protected photoreceptors.},
}
@article {pmid39251759,
year = {2024},
author = {Yoon, JM and Eun, Y and Han, K and Kim, BS and Jung, W and Kim, H and Shin, DW and Lim, DH},
title = {Association of rheumatoid arthritis with age-related macular degeneration in nationwide longitudinal cohort study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {20997},
pmid = {39251759},
issn = {2045-2322},
support = {NRF-2021R1C1C1007795//National Research Foundation of Korea/ ; HI20C1073//Korea Health Industry Development Institute/ ; },
mesh = {*Arthritis, Rheumatoid/complications/epidemiology ; *Macular Degeneration/complications/epidemiology ; Longitudinal Studies ; Cohort Studies ; Humans ; Male ; Female ; Middle Aged ; Aged ; Persons with Visual Disabilities ; Probability ; Republic of Korea/epidemiology ; },
abstract = {Previous studies on the association between age-related macular degeneration (AMD) and rheumatoid arthritis (RA) have shown conflicting results. We sought to assess the association between AMD with/without visual disability (VD) and the risk of RA using National Health Insurance data in South Korea. In total, 3,537,293 individuals who underwent health checkups in 2009 were included and followed until 2019. Participants with VD were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without VD groups. In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of VD (aHR 1.11; 95% CI 1.02-1.21). Among individuals with AMD, different risk levels of RA were observed between those without VD (aHR 1.13; 95% CI 1.03-1.21) and those with VD (aHR 0.90; 95% CI 0.64-1.27). AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities.},
}
@article {pmid39250120,
year = {2024},
author = {Todoroki, T and Takeuchi, J and Ota, H and Nakano, Y and Sajiki, AF and Nakamura, K and Kaneko, H and Nishiguchi, KM},
title = {Aqueous Humor Cytokine Analysis in Age-Related Macular Degeneration After Switching From Aflibercept to Faricimab.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {11},
pages = {15},
pmid = {39250120},
issn = {1552-5783},
mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Aqueous Humor/metabolism ; Male ; Female ; Aged ; Prospective Studies ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; *Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis/metabolism/physiopathology ; *Cytokines/metabolism ; Angiopoietin-2/metabolism ; Drug Substitution ; Placenta Growth Factor/metabolism ; Middle Aged ; },
abstract = {PURPOSE: To examine the changes in aqueous humor cytokine levels and clinical outcomes of switching from aflibercept to faricimab in eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Fifty-four eyes of 54 patients with AMD undergoing treatment with aflibercept under a treat-and-extend (TAE) regimen were switched to faricimab and studied prospectively. Best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status were analyzed using optical coherence tomography. Aqueous humor was collected before and after the switch, and angiopoietin-2 (Ang-2), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) A levels were measured.<br><br>RESULTS: After switching from aflibercept to faricimab, exudative changes improved in&#xa0;28 eyes (52%), remained stable in eight eyes (15%), and worsened in&#xa0;18 eyes (33%). BCVA changed from 0.27 &#xb1; 0.31 to 0.26 &#xb1; 0.29 (P = 0.46), CRT decreased from 306.2 &#xb1; 147.5 &#xb5;m to 278.6 &#xb1; 100.4 &#xb5;m (P = 0.11), and CCT changed from 189.5 &#xb1; 92.8 &#xb5;m to 186.8 &#xb1; 93.9 &#xb5;m (P = 0.21). VEGF-A levels&#xa0;were below the detection sensitivity&#xa0;in many cases throughout the pre- and post-switching periods. Ang-2 significantly decreased from 23.8 &#xb1; 23.5 pg/mL to 16.4 &#xb1; 21.9 pg/mL (P < 0.001), and PlGF&#xa0;significantly increased from 0.86 &#xb1; 0.85 pg/mL to 1.72 &#xb1; 1.39 pg/mL (P < 0.001).<br><br>CONCLUSIONS: Switching from aflibercept to faricimab in patients with nAMD may not only suppress VEGF-A but also Ang-2 and reduce exudative changes.},
}
@article {pmid39243634,
year = {2024},
author = {de Oliveira Figueiredo, EC and Bucolo, C and Eandi, CM},
title = {Therapeutic innovations for geographic atrophy: A promising horizon.},
journal = {Current opinion in pharmacology},
volume = {78},
number = {},
pages = {102484},
doi = {10.1016/j.coph.2024.102484},
pmid = {39243634},
issn = {1471-4973},
mesh = {Humans ; *Geographic Atrophy/therapy/drug therapy ; Animals ; *Genetic Therapy/methods ; Artificial Intelligence ; Cell- and Tissue-Based Therapy/methods ; },
abstract = {This mini review spotlights the most promising treatments for geographic atrophy, the advanced form of age-related macular degeneration, often resulting in severe and irreversible vision loss. The pathophysiology is complex, and various therapeutic strategies, including anticomplement therapies, gene therapies, cell-based interventions, and artificial intelligence-driven diagnostics are discussed. Anticomplement therapies (antifactors C3 and C5) showed promise in reducing the inflammatory response and the progression of the atrophy. Gene therapies, targeting specific genetic mutations, are under development to correct underlying defects and potentially reverse disease progression. Cell-based therapies are gaining momentum, with early studies indicating encouraging results in the replacement of damaged retinal pigment epithelium cells.},
}
@article {pmid39243285,
year = {2025},
author = {Szeps, A and Suarez, JM and Torres, R and Iribarren, R},
title = {Choroidal Control Technology: New Horizons in Maculopathy and Presbyopia.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {2},
pages = {581-588},
pmid = {39243285},
issn = {1435-702X},
mesh = {Humans ; *Presbyopia/physiopathology/therapy/complications/diagnosis ; Aged ; *Choroid/pathology/diagnostic imaging ; Male ; Middle Aged ; Female ; Aged, 80 and over ; Pilot Projects ; *Tomography, Optical Coherence/methods ; *Macular Degeneration/physiopathology/complications/diagnosis ; *Visual Acuity ; *Eyeglasses ; *Refraction, Ocular/physiology ; Axial Length, Eye/pathology/diagnostic imaging ; Follow-Up Studies ; Biometry ; },
abstract = {OBJECTIVE: To evaluate changes in choroidal thickness in presbyopes, when reading with regular glasses versus choroidal control glasses, in patients with or without Age-Related Macular Degeneration (AMD).<br><br>METHODS: This was a pilot study on short-term axial length (AL) in 33 eyes of 24 presbyopic patients aged 60 to 80&#xa0;years, assigned to two age-matched groups, with or without AMD. About them, changes in choroidal thickness were evaluated with ocular biometry through indirect measurements of axial length at baseline, after 20' of reading with conventional lenses, and after another 20' of reading with peripheral hyperopic defocus glasses. The differences in axial length between the three different times were analyzed.<br><br>RESULTS: In presbyopes without AMD there was a significant axial length shortening of -13.44 microns in the first conventional reading period, which was reversed by 90% with hyperopic defocus lenses, recovering&#x2009;+&#x2009;12.11 microns by axial lengthening (choroidal thinning, p&#x2009;=&#x2009;0.03). In patients with AMD, axial shortening was significantly greater than controls, -23.86 microns with conventional lenses (p&#x2009;<&#x2009;0.001) and they, also increased their axial length with defocus, although this response was smaller in proportion (+&#x2009;15.52 microns).<br><br>CONCLUSION: Reading with positive lenses produces myopic defocus and choroidal thickening in presbyopes with and without AMD but was significantly greater in the latter. Glasses with Choroidal Control Technology reduced thickening during reading.<br><br>KEY MESSAGES: What is known &#x2022; Presbyopia spectacles for near produce myopic defocus and choroidal thickening. What is new &#x2022; There are differences in choroidal thickening during reading between normal subjects and those with age related macular degeneration. &#x2022; Spectacles with Defocus Choroidal Control Technology reduce choroidal thickening during reading in presbyopes.},
}
@article {pmid39241860,
year = {2024},
author = {Pilotto, E and Parolini, F and Midena, G and Cosmo, E and Midena, E},
title = {Small Hyperreflective Retinal Foci as in vivo imaging feature of resident microglia activation in geographic atrophy.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110064},
doi = {10.1016/j.exer.2024.110064},
pmid = {39241860},
issn = {1096-0007},
mesh = {Humans ; *Geographic Atrophy/pathology/diagnosis ; *Tomography, Optical Coherence/methods ; *Microglia/pathology ; Female ; Male ; Aged ; Retrospective Studies ; *Fluorescein Angiography/methods ; Aged, 80 and over ; Middle Aged ; Visual Acuity/physiology ; Retina/pathology ; },
abstract = {Geographic atrophy (GA), the atrophic late stage of age-related macular degeneration (AMD), is one of the leading causes of vision loss in developed countries. Based on genetic, histological and preclinical studies, the role of the innate immune system in the development and progression of GA is well established. Microglia, the principal resident immune cells, are recognized as key players in innate immunity and contributors to AMD development. Optical coherence tomography (OCT) allows to identify small hyperreflective retinal foci (HRF) with specific features known as aggregates of activated microglial cells as possible in vivo imaging feature of local neuroretinal inflammation. The purpose of this study was to evaluate the presence and amount of small HRF in the eyes of patients with different macular atrophic phenotypes. Patients with GA in both eyes (bilateral GA: B-GA group), patients with GA in one eye and macular new vessels (MNV) in the fellow-eye (unilateral GA: U-GA group) and patients with extensive macular atrophy with pseudodrusen (EMAP), a rare and aggressive variant of atrophic AMD, were retrospectively analyzed. HRF, defined as isolated punctiform elements of small dimensions (≤30 μm) with intermediate reflectivity (similar to that of the nerve fiber layer) and without a shadow cone, were manually identified and quantified. The amount of HRF was correlated to best corrected visual acuity (BCVA), GA lesion size, measured both at near infrared reflectance (NIR), and blue wavelength fundus autofluorescence (FAF) images, to some GA features (multifocal versus unifocal GA; presence versus absence of foveal sparing) and to central retinal thickness (CRT). Forty-six patients (26 in the B-GA group, 16 in the U-GA group and 4 in the EMAP group) were studied. Patients with EMAP were younger compared to patients with B-GA and to patients with U-GA (63.5 ± 6.8 years vs 80.4 ± 8.4 years B-GA, and vs 83.3 ± 6.1 years U-GA; p = 0.0004 and p= <0.0001, respectively). Mean BCVA, mean GA area at NIR and at FAF images, foveal sparing and multifocal versus unifocal GA distribution and mean CRT were not significantly different among groups. GA area was wider on NIR versus FAF in all groups, significantly in B-GA and U-GA groups (11.7 ± 7.6 mm[2] vs 10.6 ± 7.1 mm[2], p = 0.0087 in B-GA; 7.8 ± 9.2 mm[2] vs 7.7 ± 9.4 mm[2], p = 0.004 in U-GA). The number of HRF was significantly higher in U-GA compared to B-GA and to EMAP (47.4 ± 7.1 vs 31.6 ± 7.3 B-GA and 28.0 ± 4.9 EMAP, p < 0.0001 for both), while mean HRF number did not significantly differ between B-GA and EMAP (p = 0.1960). HRF count correlated only to CRT, positively in B-GA and negatively in U-GA group. The increase of small HRF, which mirrors retinal microglial activation, characterizes eyes with unilateral GA (and MNV in the fellow eye) but not eyes with bilateral GA or EMAP. The role of activated microglia in the retina of GA eyes needs to be better investigated, mainly considering the actual and new therapeutic strategies with which to reduce either the development or progression of the atrophic macular changes.},
}
@article {pmid39240551,
year = {2024},
author = {Choi, YJ and Kim, HM and Na, TY and Park, KH and Park, SG and Woo, SJ},
title = {Intraocular Concentration of Stem Cell Factor/c-KIT and Galectin-1 in Retinal Diseases.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {11},
pages = {11},
pmid = {39240551},
issn = {1552-5783},
mesh = {Humans ; *Galectin 1/metabolism ; *Stem Cell Factor/metabolism ; Male ; Aged ; Female ; *Proto-Oncogene Proteins c-kit/metabolism ; *Vascular Endothelial Growth Factor A/metabolism ; Middle Aged ; Aqueous Humor/metabolism ; Aged, 80 and over ; Retinal Diseases/metabolism/drug therapy ; Macular Edema/metabolism/drug therapy ; Retinal Vein Occlusion/metabolism/drug therapy ; Diabetic Retinopathy/metabolism/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Macular Degeneration/metabolism/drug therapy ; Intravitreal Injections ; },
abstract = {PURPOSE: To investigate the intraocular concentration profiles of stem cell factor (SCF)/c-KIT, galectin-1 (GAL-1), and vascular endothelial growth factor (VEGF)-A with regard to retinal disease and treatment response.<br><br>METHODS: The study group included 13 patients with dry age-related macular degeneration (AMD), 196 with neovascular AMD (nAMD), 21 with diabetic macular edema (DME), 10 with retinal vein occlusion (RVO), and 34 normal subjects with cataracts. Aqueous humor levels of SCF, c-KIT, GAL-1, and VEGF-A were analyzed by immunoassay according to disease group and treatment response.<br><br>RESULTS: Increased aqueous levels of SCF, c-KIT, and GAL-1 were observed in eyes with nAMD (2.67 &#xb1; 3.66, 296.84 &#xb1; 359.56, and 3945.61 &#xb1; 5976.2 pg/mL, respectively), DME (1.64 &#xb1; 0.89, 238.80 &#xb1; 265.54, and 3701.23 &#xb1; 4340.54 pg/mL, respectively), and RVO (4.62 &#xb1; 8.76, 509.63 &#xb1; 647.58, and 9079.60 &#xb1; 11909.20 pg/mL, respectively) compared with controls (1.13 &#xb1; 0.24, 60.00 &#xb1; 0.00, and 613.27 &#xb1; 1595.12 pg/mL, respectively). In the eyes of nAMD, the levels of all three cytokines correlated positively with VEGF-A levels. After intravitreal injections of anti-VEGF agents, the levels of GAL-1 and VEGF-A decreased significantly, whereas those of SCF and c-Kit showed no significant change. Eyes of nAMD patients with improved vision after treatment had significantly lower levels of c-KIT, GAL-1, and VEGF-A at baseline.<br><br>CONCLUSIONS: The intraocular levels of cytokines were significantly elevated in eyes with nAMD, DME, and RVO compared to the controls and they showed different response to anti-VEGF treatment. With this result and their known association with angiogenesis, these cytokines may be potential therapeutic targets for future research.},
}
@article {pmid39240520,
year = {2025},
author = {Hernández-Núñez, I and Clark, BS},
title = {Experimental Framework for Assessing Mouse Retinal Regeneration Through Single-Cell RNA-Sequencing.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2848},
number = {},
pages = {117-134},
pmid = {39240520},
issn = {1940-6029},
mesh = {Animals ; Mice ; *Single-Cell Analysis/methods ; *Retina/metabolism ; *Ependymoglial Cells/metabolism ; Regeneration/genetics ; Sequence Analysis, RNA/methods ; Retinal Degeneration/genetics/therapy ; RNA-Seq/methods ; Disease Models, Animal ; },
abstract = {Retinal degenerative diseases including age-related macular degeneration and glaucoma are estimated to currently affect more than 14 million people in the United States, with an increased prevalence of retinal degenerations in aged individuals. An expanding aged population who are living longer forecasts an increased prevalence and economic burden of visual impairments. Improvements to visual health and treatment paradigms for progressive retinal degenerations slow vision loss. However, current treatments fail to remedy the root cause of visual impairments caused by retinal degenerations-loss of retinal neurons. Stimulation of retinal regeneration from endogenous cellular sources presents an exciting treatment avenue for replacement of lost retinal cells. In multiple species including zebrafish and Xenopus, Müller glial cells maintain a highly efficient regenerative ability to reconstitute lost cells throughout the organism's lifespan, highlighting potential therapeutic avenues for stimulation of retinal regeneration in humans. Here, we describe how the application of single-cell RNA-sequencing (scRNA-seq) has enhanced our understanding of Müller glial cell-derived retinal regeneration, including the characterization of gene regulatory networks that facilitate/inhibit regenerative responses. Additionally, we provide a validated experimental framework for cellular preparation of mouse retinal cells as input into scRNA-seq experiments, including insights into experimental design and analyses of resulting data.},
}
@article {pmid39240279,
year = {2025},
author = {Zhang, Z and Bao, S and Yan, D and Zhai, M and Qu, J and Zhou, M},
title = {Causal Relationships Between Retinal Diseases and Psychiatric Disorders Have Implications for Precision Psychiatry.},
journal = {Molecular neurobiology},
volume = {62},
number = {3},
pages = {3182-3194},
pmid = {39240279},
issn = {1559-1182},
support = {HNLC2022RWS002//Real World Study Project of Hainan Boao Lecheng Pilot Zone(Real World Study Base of NMPA&#xff09;/ ; },
mesh = {Humans ; *Mental Disorders/genetics/complications ; *Retinal Diseases/genetics/complications ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Precision Medicine/methods ; Genetic Predisposition to Disease ; Risk Factors ; },
abstract = {Observational studies and clinical trials have reported potential associations between retinal diseases and psychiatric disorders. However, the causal associations between them have remained elusive. In this study, we used bi-directional two-sample Mendelian randomization (MR) analysis to explore unconfounded causal relationships between retinal diseases and psychiatric disorders using large-scale genome-wide association study (GWAS) summary statistics of over 500,000 participants of European ancestry from the FinnGen project, the Psychiatric Genomics Consortium, the European Bioinformatics Institute, and the UK Biobank. Our MR analysis revealed significant causal relationships between major retinal diseases and specific psychiatric disorders. Specifically, susceptibility to dry age-related macular degeneration was associated with a reduced risk of anorexia nervosa (OR = 0.970; 95% CI = 0.930 ~ 0.994; P = 0.025). Furthermore, we found some evidence that exposure to diabetic retinopathy was associated with an increased risk of schizophrenia (OR = 1.021; 95% CI 1.012 ~ 1.049; P = 0.001), and exposure to retinal detachments and breaks was associated with an increased risk of attention deficit hyperactivity disorder (OR = 1.190; 95% CI 1.063 ~ 1.333; P = 0.003). These causal relationships were not confounded by biases of pleiotropy and reverse causation. Our study highlights the importance of preventing and managing retinal disease as a potential avenue for improving the prevention, management and treatment of major psychiatric disorders.},
}
@article {pmid39239631,
year = {2024},
author = {Tokuc, EO and Seyyar, SA and Basaran, E and Ozdemir, SN and Karabas, L},
title = {A Comprehensive Evaluation of Serum Iron Status Indicators in Patients with Age-Related Macular Degeneration.},
journal = {Beyoglu eye journal},
volume = {9},
number = {3},
pages = {149-154},
pmid = {39239631},
issn = {2587-0394},
abstract = {OBJECTIVES: Iron is recognized as a significant contributor to oxidative damage, and its levels tend to rise with age, potentially worsening age-related diseases. The aim of this study was to investigate the role of serum iron metabolism markers in the pathogenesis of age-related macular degeneration (AMD).<br><br>METHODS: The files of all AMD patients in Kocaeli University School of Medicine between January 2017 and March 2020 were reviewed retrospectively. By examining the files of AMD patients who applied to the eye outpatient clinic on the same dates, those dry AMD (dAMD) and neovascular AMD (nAMD) were recorded. As a control group, the records of patients without any AMD findings were obtained from the files of all patients who visited the clinic during the same time period. All records were recorded for analysis, including a comprehensive ophthalmological examination, laboratory data of fasting blood tests, and an internal medicine outpatient examination.<br><br>RESULTS: Of the 164 participants, 50 were dAMD patients, 51 were nAMD patients, and 63 were patients non-AMD (control group). There was a significant difference between the groups' mean corpuscular volume (MCV), serum ferritin, and total iron-binding capacity (TIBC) (p<0.050). It was observed that the ferritin of those with AMD was significantly higher than the control group, whereas MCV and TIBC were found to be significantly lower (p<0.050). There was no significant difference in serum iron marker levels between nAMD and dAMD patients (p>0.05).<br><br>CONCLUSION: Assessing serum iron status indicators during the routine monitoring of AMD may provide insights into the associated risk profile of the condition.},
}
@article {pmid39238056,
year = {2024},
author = {Koc, H and Uzunoğlu, S},
title = {A potential biomarker for age-related macular degeneration disease: iris freckles.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {62},
pmid = {39238056},
issn = {2056-9920},
abstract = {BACKGRAUND: To determine the potential relationship between age-related macular degeneration and iris freckles.<br><br>METHOD: In this case-control study, iris photographs of 300 eyes of 300 patients diagnosed with age-related macular degeneration and 300 eyes of 300 healthy volunteers were obtained with the help of a high-resolution mobile phone camera. The evaluated iris photographs were classified according to the Descriptive Iris Color Classification Scale.<br><br>RESULTS: The average age of the AMD group is 73.05&#x2009;&#xb1;&#x2009;6.93, and the average age of the control group is 73.43&#x2009;&#xb1;&#x2009;5.72. (p&#x2009;=&#x2009;0.124) While freckles were present in 200 (66.7%) of the patients in the AMD group, freckles were not observed in 100 patients (33.3%) of AMD group. While freckles were present in 142 (47.3%) of the patients in the control group, freckles were not observed in 158 of control group(52.7%). There was a significant difference in the presence of freckles between the two groups. (p&#x2009;<&#x2009;0.001) The average number of freckles in the AMD group was 3.97&#x2009;&#xb1;&#x2009;3.07, and the number of freckles in the control group was 3.06&#x2009;&#xb1;&#x2009;2.55. (p&#x2009;=&#x2009;0.001) CONCLUSION: We think that evaluation of iris details, especially the presence of iris freckles, should be used routinely in age-related macular degeneration screening. The risk of age-related macular degeneration can be predicted by evaluating iris details, which is an easy and inexpensive method.},
}
@article {pmid39237835,
year = {2024},
author = {Sagong, M and Kim, JH and Woo, SJ and Kim, YC and Cho, H and Lee, YH and Byon, I and Jo, YJ and Chin, HS and Kim, J and Chae, JE and Kang, SW},
title = {Predictors of Disease Activity After Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration Using Real-World Data from the PROOF Study.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {11},
pages = {2839-2853},
pmid = {39237835},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions.<br><br>METHODS: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12&#xa0;months of which 453 patients (cohort 2) were followed-up for 24&#xa0;months from baseline.<br><br>RESULTS: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P&#x2009;=&#x2009;0.0494) and retinal fluid at month 3 after loading phase (P&#x2009;=&#x2009;0.0082). The mean changes in visual acuity were&#x2009;+&#x2009;6.2,&#x2009;+&#x2009;10.1, and&#x2009;+&#x2009;13.3 letters and in the central subfield thickness were -&#x2009;79.1&#xa0;&#xb5;m, -&#x2009;96.3&#xa0;&#xb5;m, and -&#x2009;134.4&#xa0;&#xb5;m at 12&#xa0;months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively.<br><br>CONCLUSIONS: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1&#xa0;year of anti-VEGF treatment.},
}
@article {pmid39237530,
year = {2024},
author = {Kim, HJ and Ryu, YK and Shin, YJ},
title = {Impact of COVID-19 pandemic on ocular disease: KNHANES 2015-2021.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {20706},
pmid = {39237530},
issn = {2045-2322},
support = {Hallym university research fund//Hallym University/ ; NRF- 2023R1A2C2002674//National Research Foundation of Korea/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; Middle Aged ; Male ; Female ; Republic of Korea/epidemiology ; Risk Factors ; Cross-Sectional Studies ; Aged ; *Cataract/epidemiology ; *Eye Diseases/epidemiology ; *Macular Degeneration/epidemiology ; Adult ; *Glaucoma/epidemiology ; Nutrition Surveys ; SARS-CoV-2/isolation &amp; purification ; Pandemics ; Aged, 80 and over ; },
abstract = {The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015-2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (< 60 and ≥ 60 years). A total of 50,158 people were diagnosed, of whom 7270 were diagnosed with cataract, 921 with glaucoma, and 439 with age-related macular degeneration (AMD). Risk factors for cataract were COVID-19 pandemic (OR 1.161), hypertension (OR 1.608), diabetes (OR 1.573), dyslipidemia (OR 1.167), stroke (OR 1.272), and depression (OR 1.567). Risk factors for AMD were COVID-19 pandemic (OR 1.600), dyslipidemia (OR 1.610), and depression (OR 1.466). Risk factors for glaucoma were hypertension (OR 1.234), dyslipidemia (OR 1.529), diabetes (OR 1.323), and depression (OR 1.830). The COVID-19 pandemic was a risk factor for cataracts and AMD, but not for glaucoma. Cataracts and AMD may be more influenced by the acquired health conditions or the environment.},
}
@article {pmid39237272,
year = {2024},
author = {Savoy, FM and Rao, DP and Toh, JK and Ong, B and Sivaraman, A and Sharma, A and Das, T},
title = {Empowering Portable Age-Related Macular Degeneration Screening: Evaluation of a Deep Learning Algorithm for a Smartphone Fundus Camera.},
journal = {BMJ open},
volume = {14},
number = {9},
pages = {e081398},
pmid = {39237272},
issn = {2044-6055},
support = {N01 EY002127/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Deep Learning ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Smartphone ; Retrospective Studies ; *Algorithms ; Aged ; Fundus Oculi ; Female ; Sensitivity and Specificity ; Photography/instrumentation ; Male ; ROC Curve ; Middle Aged ; Mass Screening/methods/instrumentation ; },
abstract = {OBJECTIVES: Despite global research on early detection of age-related macular degeneration (AMD), not enough is being done for large-scale screening. Automated analysis of retinal images captured via smartphone presents a potential solution; however, to our knowledge, such an artificial intelligence (AI) system has not been evaluated. The study aimed to assess the performance of an AI algorithm in detecting referable AMD on images captured on a portable fundus camera.<br><br>DESIGN, SETTING: A retrospective image database from the Age-Related Eye Disease Study (AREDS) and target device was used.<br><br>PARTICIPANTS: The algorithm was trained on two distinct data sets with macula-centric images: initially on 108,251 images (55% referable AMD) from AREDS and then fine-tuned on 1108 images (33% referable AMD) captured on Asian eyes using the target device. The model was designed to indicate the presence of referable AMD (intermediate and advanced AMD). Following the first training step, the test set consisted of 909 images (49% referable AMD). For the fine-tuning step, the test set consisted of 238 (34% referable AMD) images. The reference standard for the AREDS data set was fundus image grading by the central reading centre, and for the target device, it was consensus image grading by specialists.<br><br>OUTCOME MEASURES: Area under receiver operating curve (AUC), sensitivity and specificity of algorithm.<br><br>RESULTS: Before fine-tuning, the deep learning (DL) algorithm exhibited a test set (from AREDS) sensitivity of 93.48% (95% CI: 90.8% to 95.6%), specificity of 82.33% (95% CI: 78.6% to 85.7%) and AUC of 0.965 (95% CI:0.95 to 0.98). After fine-tuning, the DL algorithm displayed a test set (from the target device) sensitivity of 91.25% (95% CI: 82.8% to 96.4%), specificity of 84.18% (95% CI: 77.5% to 89.5%) and AUC 0.947 (95% CI: 0.911 to 0.982).<br><br>CONCLUSION: The DL algorithm shows promising results in detecting referable AMD from a portable smartphone-based imaging system. This approach can potentially bring effective and affordable AMD screening to underserved areas.},
}
@article {pmid39236688,
year = {2024},
author = {Toto, L and Formenti, F and Ruggeri, ML and Quarta, A and Romano, A and De Nicola, C and Belloni Baroni, L and Porreca, A and Di Nicola, M and Mastropasqua, R},
title = {Efficacy and Durability of Faricimab in Naïve Eyes with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {528-536},
doi = {10.1159/000540194},
pmid = {39236688},
issn = {1423-0259},
mesh = {Humans ; Male ; Female ; *Tomography, Optical Coherence/methods ; *Visual Acuity ; *Intravitreal Injections ; Aged ; *Fluorescein Angiography/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged, 80 and over ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; Fundus Oculi ; Prospective Studies ; Macula Lutea/pathology/diagnostic imaging ; },
abstract = {INTRODUCTION: The aim of the study was to evaluate functional and anatomical changes in patients with neovascular age-related macular degeneration (nAMD) treated with a loading dose of faricimab intravitreal injections (IVIs).<br><br>METHODS: Eighteen eyes of 18 patients with active macular neovascularization and nAMD were enrolled at the Ophthalmology Clinic of University G. D'Annunzio, Chieti-Pescara, Italy. All patients were scheduled for faricimab IVI as per label. Enrolled patients underwent complete ophthalmic evaluation, including optical coherence tomography, fluorescein angiography, and indocyanine green angiography. All measurements were evaluated at baseline (T0) and then monthly up to week 20 (T4). Main outcome measures were changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachments (PEDs) presence and maximum height (PED-MH), intraretinal fluid (IRF) presence, subfoveal subretinal fluid (SSRF) presence and thickness.<br><br>RESULTS: BCVA improved and CMT reduced significantly during follow-up (p < 0.001). In addition, SFCT decreased significantly (p = 0.031). Between T0 and T4, SSRF presence reduced from 55.6 to 16.7% (p = 0.045); IRF presence changed from 50 to 22.2%, respectively (p = 0.074). PED-MH was reduced in 58.8% of patients at T4. At week 20, 72.3% of patients were in the q12/q16 interval.<br><br>CONCLUSION: Faricimab showed efficacy in the treatment of na&#xef;ve nAMD patients with an improvement of anatomical and functional parameters and a treatment interval after the loading phase equal or greater than 12 weeks in the majority of patients.},
}
@article {pmid39235669,
year = {2024},
author = {Aldhanhani, AA and Azzam, OA and AlAli, SH and Almasri, KG and Aljneibi, SH and Pichi, F},
title = {Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {369},
pmid = {39235669},
issn = {1573-2630},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; *Intravitreal Injections ; *Tomography, Optical Coherence/methods ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Drug Substitution/methods ; Treatment Outcome ; Follow-Up Studies ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; },
abstract = {PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative.<br><br>METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT).<br><br>RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF).<br><br>CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.},
}
@article {pmid39235545,
year = {2024},
author = {Deng, J and Qin, Y},
title = {Advancements and emerging trends in ophthalmic anti-VEGF therapy: a bibliometric analysis.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {368},
pmid = {39235545},
issn = {1573-2630},
support = {2022ZYX04//The Open Fund Project of First-Class Disciplines of Hunan University of Chinese Medicine/ ; ZK1801YK015//The Key Discipline Construction Project of Ophthalmology of Traditional Chinese Medicine of the National Administration of Traditional Chinese Medicine/ ; },
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Bibliometrics ; Ophthalmology/trends ; Intravitreal Injections ; },
abstract = {INTRODUCTION: Vascular Endothelial Growth Factor (VEGF) is associated with abnormal fundus neovascularization. Consequently, Anti-VEGF agents are vital for ophthalmic treatment. This paper reviews the application of anti-VEGF agents in ophthalmology over the past two decades with the aim of providing insights for further research.<br><br>METHODS: A meticulous search strategy was employed in the Web of Science Core Collection literature from 2003 to 2023 to gather relevant literature, which was then analyzed using VOSviewer, CiteSpace, and the R package Bibliometrix.<br><br>RESULTS: The study included 3,602 publications from 83 countries and 3,445 institutions. The United States and China have emerged as leading contributors in terms of the publication volume. Johns Hopkins University, the University of Sydney, and Genentech Inc were identified as frontrunners in this field. "Retina" had the highest publication volume, whereas "Ophthalmology" had the highest citation frequency. Among the 15,918 scholars, Bressler NM, Holz FG, Glassman AR, and Bandello F led in publication volume, while Brown DM was the most cited author. High-frequency keywords included "Endothelial Growth Factor," "Therapy," "Safety," and "Randomized Clinical Trial."<br><br>CONCLUSION: Anti-VEGF drugs have shown notable success in treating neovascular eye diseases, especially wet age-related macular degeneration and diabetic macular edema, focusing on clinical efficacy, injection regimens, and safety. Future directions include developing new anti-VEGF drugs, drug delivery systems, non-invasive administration, multi-target drugs, leveraging big data and artificial intelligence, and addressing the current treatment limits. Continuous innovation and method improvement in this field promise more breakthroughs, providing effective, safe, and economical options for eye disease treatment.},
}
@article {pmid39235402,
year = {2024},
author = {de Vente, C and Valmaggia, P and Hoyng, CB and Holz, FG and Islam, MM and Klaver, CCW and Boon, CJF and Schmitz-Valckenberg, S and Tufail, A and Saßmannshausen, M and Sánchez, CI and , },
title = {Generalizable Deep Learning for the Detection of Incomplete and Complete Retinal Pigment Epithelium and Outer Retinal Atrophy: A MACUSTAR Report.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {9},
pages = {11},
pmid = {39235402},
issn = {2164-2591},
mesh = {*Deep Learning ; Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Female ; *Macular Degeneration/pathology/diagnosis/diagnostic imaging ; Male ; Aged ; Atrophy/pathology ; Algorithms ; Aged, 80 and over ; },
abstract = {PURPOSE: The purpose of this study was to develop a deep learning algorithm for detecting and quantifying incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) in optical coherence tomography (OCT) that generalizes well to data from different devices and to validate in an intermediate age-related macular degeneration (iAMD) cohort.<br><br>METHODS: The algorithm comprised a domain adaptation (DA) model, promoting generalization across devices, and a segmentation model for detecting granular biomarkers defining iRORA/cRORA, which are combined into iRORA/cRORA segmentations. Manual annotations of iRORA/cRORA in OCTs from different devices in the MACUSTAR study (168 patients with iAMD) were compared to the algorithm's output. Eye level classification metrics included sensitivity, specificity, and quadratic weighted Cohen's &#x3ba; score (&#x3ba;w). Segmentation performance was assessed quantitatively using Bland-Altman plots and qualitatively.<br><br>RESULTS: For ZEISS OCTs, sensitivity and specificity for iRORA/cRORA classification were 38.5% and 93.1%, respectively, and 60.0% and 96.4% for cRORA. For Spectralis OCTs, these were 84.0% and 93.7% for iRORA/cRORA, and 62.5% and 97.4% for cRORA. The &#x3ba;w scores for 3-way classification (none, iRORA, and cRORA) were 0.37 and 0.73 for ZEISS and Spectralis, respectively. Removing DA reduced &#x3ba;w from 0.73 to 0.63 for Spectralis.<br><br>CONCLUSIONS: The DA-enabled iRORA/cRORA segmentation algorithm showed superior consistency compared to human annotations, and good generalization across OCT devices.<br><br>TRANSLATIONAL RELEVANCE: The application of this algorithm may help toward precise and automated tracking of iAMD-related lesion changes, which is crucial in clinical settings and multicenter longitudinal studies on iAMD.},
}
@article {pmid39235401,
year = {2024},
author = {Meng, J and Song, Y and He, W and Lu, ZL and Chen, Y and Wei, L and Zhang, K and Qi, J and Du, Y and Lu, Y and Zhu, X},
title = {A Novel Artificial Intelligence-Based Classification of Highly Myopic Eyes Based on Visual Function and Fundus Features.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {9},
pages = {12},
pmid = {39235401},
issn = {2164-2591},
mesh = {Humans ; *Artificial Intelligence ; Female ; Male ; Middle Aged ; *Tomography, Optical Coherence/methods ; *Fundus Oculi ; Aged ; *Contrast Sensitivity/physiology ; Visual Acuity/physiology ; Adult ; Myopia, Degenerative/physiopathology/diagnostic imaging/diagnosis/classification/pathology ; Macular Degeneration/classification/physiopathology/diagnosis/pathology/diagnostic imaging ; Macula Lutea/pathology/diagnostic imaging/physiopathology ; Nerve Fibers/pathology ; },
abstract = {PURPOSE: To develop a novel classification of highly myopic eyes using artificial intelligence (AI) and investigate its relationship with contrast sensitivity function (CSF) and fundus features.<br><br>METHODS: We enrolled 616 highly myopic eyes of 616 patients. CSF was measured using the quantitative CSF method. Myopic macular degeneration (MMD) was graded according to the International META-PM Classification. Thickness of the macula and peripapillary retinal nerve fiber layer (p-RNFL) were assessed by fundus photography and optical coherence tomography, respectively. Classification was performed by combining CSF and fundus features with principal component analysis and k-means clustering.<br><br>RESULTS: With 83.35% total variance explained, highly myopic eyes were classified into four AI categories. The percentages of AI categories 1 to 4 were 14.9%, 37.5%, 36.2%, and 11.4%, respectively. Contrast acuity of the eyes in AI category 1 was the highest, which decreased by half in AI category 2. For AI categories 2 to 4, every increase in category led to a decrease of 0.23 logarithm of the minimum angle of resolution in contrast acuity. Compared with those in AI category 1, eyes in AI category 2 presented a higher percentage of MMD2 and thinner temporal p-RNFL. Eyes in AI categories 3 and 4 presented significantly higher percentage of MMD &#x2265; 3, thinner nasal macular thickness and p-RNFL (P < 0.05). Multivariate regression showed AI category 4 had higher MMD grades and thinner macular compared with AI category 3.<br><br>CONCLUSIONS: We proposed an AI-based classification of highly myopic eyes with clear relevance to visual function and fundus features.<br><br>TRANSLATIONAL RELEVANCE: This classification helps to discover the early hidden visual deficits of highly myopic patients, becoming a useful tool to evaluate the disease comprehensively.},
}
@article {pmid39233867,
year = {2024},
author = {Tian, Z and Liu, Q and Lin, HY and Zhu, YR and Ling, L and Sung, TC and Wang, T and Li, W and Gao, M and Cheng, S and Renuka, RR and Subbiah, SK and Fan, G and Wu, GJ and Higuchi, A},
title = {Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.},
journal = {Regenerative biomaterials},
volume = {11},
number = {},
pages = {rbae091},
pmid = {39233867},
issn = {2056-3418},
abstract = {Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.},
}
@article {pmid39232385,
year = {2024},
author = {Yeh, KL and Wu, SW and Chiang, CY and Chen, CJ and Chen, WY and Tseng, CC and Kuan, YH and Chou, CC},
title = {Enhancing ocular protection against UVB: The role of irigenin in modulating oxidative stress and apoptotic pathways In Vivo.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {179},
number = {},
pages = {117346},
doi = {10.1016/j.biopha.2024.117346},
pmid = {39232385},
issn = {1950-6007},
mesh = {*Oxidative Stress/drug effects/radiation effects ; *Apoptosis/drug effects/radiation effects ; Animals ; *Ultraviolet Rays/adverse effects ; DNA Damage/drug effects ; Antioxidants/pharmacology ; Male ; Mice ; Mitochondria/drug effects/metabolism/pathology/radiation effects ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects ; NF-E2-Related Factor 2/metabolism ; },
abstract = {Oxidative damage contributes to age-related macular degeneration. Irigenin possesses diverse pharmacologic properties, including antioxidative and antiapoptotic effects. Our in vivo experiments indicated that irigenin mitigates UVB-induced histopathologic changes and oxidative DNA damage. Histologic analyses and TUNEL staining revealed that this compound dose-dependently ameliorated UVB-induced retinal damage and apoptosis. Furthermore, irigenin substantially reduced the level of 8-hydroxyguanosine, a biomarker of UVB-induced oxidative DNA damage. We further explored the molecular mechanisms that mediate the protective effects of irigenin. Our findings suggested that UVB-induced generation of ROS disrupts the stability of the mitochondrial membrane, activating intrinsic apoptotic pathways; the underlying mechanisms include the release of cytochrome c, activation of caspase-9 and caspase-3, and subsequent degradation of PARP-1. Notably, irigenin reversed mitochondrial disruption and apoptosis. It also modulated the Bax and Bcl-2 expression but influenced the mitochondrial apoptotic pathways. Our study highlights the role of the Nrf2 pathway in mitigating the effects of oxidative stress. We found that UVB exposure downregulated, but irigenin treatment upregulated the expression of Nrf2 and antioxidant enzymes. Therefore, irigenin activates the Nrf2 pathway to address oxidative stress. In conclusion, irigenin exhibits protective effects against UVB-induced ocular damage, evidenced by the diminution of histological alterations. It mitigates oxidative DNA damage and apoptosis in the retinal tissues by modulating the intrinsic apoptotic pathways and the AIF mechanisms. Furthermore, irigenin effectively reduces lipid peroxidation, enhancing the activity of antioxidant enzymes by stimulating the Nrf2 pathway. This protective mechanism underscores the potential benefit of irigenin in combating UVB-mediated ocular damage.},
}
@article {pmid39231110,
year = {2024},
author = {Warter, A and Heinke, A and Cavichini, M and Galang, CMB and Kalaw, FGP and Bartsch, DU and Cheng, L and Freeman, WR},
title = {Simultaneous Intravitreal Steroid and Anti-VEGF Therapy for Monotherapy-Resistant Chronic Wet Age-Related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {12},
pages = {698-704},
doi = {10.3928/23258160-20240705-03},
pmid = {39231110},
issn = {2325-8179},
mesh = {Humans ; *Intravitreal Injections ; Retrospective Studies ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Visual Acuity ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Aged ; *Glucocorticoids/administration &amp; dosage ; *Tomography, Optical Coherence/methods ; Aged, 80 and over ; Drug Therapy, Combination ; Chronic Disease ; Ranibizumab/administration &amp; dosage ; Fluorescein Angiography/methods ; Drug Resistance ; Bevacizumab/administration &amp; dosage ; Middle Aged ; Treatment Outcome ; },
abstract = {BACKGROUND AND OBJECTIVE: The purpose of this study was to analyze the safety and efficacy of combined intravitreal anti-vascular endothelial growth factor (anti-VEGF) and steroid therapeutic agents for resistant choroidal neovascularization (CNV). A retrospective observational clinical study was performed assessing anatomic and visual changes in a consecutive cohort of patients with refractory chronic wet age-related macular degeneration resistant to high-dose aflibercept therapy.<br><br>PATIENTS AND METHODS: Twelve eyes of 12 patients with unresponsive CNV despite aggressive monthly anti-VEGF (4-mg aflibercept [mean: 43.75 &#xb1; SD23.08]) were included. Combination consisted of simultaneous administration of anti-VEGF and corticosteroids. Study measures evaluated visual acuity, central retinal thickness (CRT), and intraocular pressure.<br><br>RESULTS: Paired tests revealed significant CRT reduction from the baseline at the 1-month (388.58 &#xb1; 89.31 versus 334.00 &#xb1; 92.88, P = 0.0117), 2-month (388.58 &#xb1; 89.31 versus 312.08 &#xb1; 75.61, P = 0.0185), and 3-month (388.53 &#xb1; 89.31 versus 304.56 &#xb1; 53.28, P = 0.046) visit. The Kaplan-Meier curve showed a median time of remission (no retinal fluid) of 70 days (95% CI 53, 147 days).<br><br>CONCLUSION: Combination treatment demonstrated clear anatomic improvement in eyes with anti-VEGF-resistant CNV. [Ophthalmic Surg Lasers Imaging Retina 2024;55:698-704.].},
}
@article {pmid39230998,
year = {2024},
author = {},
title = {Erratum in: Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {11},
pages = {6},
doi = {10.1167/iovs.65.11.6},
pmid = {39230998},
issn = {1552-5783},
}
@article {pmid39227909,
year = {2024},
author = {Mukai, R and Honjo, J and Tanaka, K and Sekiryu, T},
title = {Exploring the comparative regressive effects of aflibercept and faricimab on pigment epithelial detachment.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {393},
pmid = {39227909},
issn = {1471-2415},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Male ; Female ; Retrospective Studies ; *Retinal Detachment/drug therapy/diagnosis ; *Intravitreal Injections ; Aged ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use ; *Retinal Pigment Epithelium/pathology/drug effects ; *Visual Acuity ; Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged, 80 and over ; Middle Aged ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {BACKGROUND: This study aimed to compare the regressive effects of aflibercept and faricimab on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration.<br><br>METHODS: In total, 41 eyes of 40 patients diagnosed with type 1 macular neovascularization were retrospectively analyzed using multimodal imaging. Of these, 23 eyes were treated with intravitreal aflibercept injections (IVA group), and 18 eyes were treated with intravitreal faricimab (IVFa group), with 3 consecutive injections administered as loading dose therapy. Before treatment and at 1, 2, and 3&#xa0;months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group.<br><br>RESULTS: In the IVA group, the MH at baseline (215&#x2009;&#xb1;&#x2009;177&#xa0;&#x3bc;m) was reduced to 141&#x2009;&#xb1;&#x2009;150 (P&#x2009;=&#x2009;0.06), 119&#x2009;&#xb1;&#x2009;150 (P&#x2009;<&#x2009;0.01), and 107&#x2009;&#xb1;&#x2009;150&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.0001) at 1, 2, and 3&#xa0;months after treatment, respectively. Similarly, in the IVFa group, the MH decreased from 240&#x2009;&#xb1;&#x2009;195&#xa0;&#xb5;m before treatment to 165&#x2009;&#xb1;&#x2009;170&#xa0;&#xb5;m (P&#x2009;=&#x2009;0.24), 139&#x2009;&#xb1;&#x2009;142&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.05), and 117&#x2009;&#xb1;&#x2009;112&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.01) at 1, 2, and 3&#xa0;months after treatment, respectively. The reduction at 2 and 3&#xa0;months was significant in both treatments. The mean changes of MH from baseline were -108&#x2009;&#xb1;&#x2009;142&#xa0;&#xb5;m in the IVA group and -124&#x2009;&#xb1;&#x2009;112&#xa0;&#xb5;m in the IVFa group, with no significant difference (P&#x2009;=&#x2009;0.21). In both groups, the MD did not regress significantly.<br><br>CONCLUSIONS: The results suggested that the MH of the PED between the IVA and IVFa groups regressed similarly after each loading therapy.},
}
@article {pmid39227682,
year = {2024},
author = {Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and Foos, E and McKeown, A and Bogunovic, H and Schmidt-Erfurth, U},
title = {Quantitative comparison of automated OCT and conventional FAF-based geographic atrophy measurements in the phase 3 OAKS/DERBY trials.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {20531},
pmid = {39227682},
issn = {2045-2322},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Disease Progression ; Fluorescein Angiography/methods ; *Geographic Atrophy/diagnostic imaging/drug therapy ; Immunoglobulin Fab Fragments ; Macular Degeneration/drug therapy/diagnostic imaging/pathology ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; },
abstract = {With the approval of the first two substances for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), a standardized monitoring of patients treated with complement inhibitors in clinical practice is needed. Optical coherence tomography (OCT) provides high-resolution access to the retinal pigment epithelium (RPE) and neurosensory layers, such as the ellipsoid zone (EZ), which further enhances the understanding of disease progression and therapeutic effects in GA compared to conventional fundus autofluorescence (FAF). In addition, artificial intelligence-based methodology allows the identification and quantification of GA-related pathology on OCT in an objective and standardized manner. The purpose of this study was to comprehensively evaluate automated OCT monitoring for GA compared to reading center-based manual FAF measurements in the largest successful phase 3 clinical trial data of complement inhibitor therapy to date. Automated OCT analysis of RPE loss showed a high and consistent correlation to manual GA measurements on conventional FAF. EZ loss on OCT was generally larger than areas of RPE loss, supporting the hypothesis that EZ loss exceeds underlying RPE loss as a fundamental pathophysiology in GA progression. Automated OCT analysis is well suited to monitor disease progression in GA patients treated in clinical practice and clinical trials.},
}
@article {pmid39226159,
year = {2024},
author = {Qin, T and Chen, T and Ma, R and Li, H and Li, C and Zhao, J and Yuan, J and Zhang, Z and Ning, X},
title = {Stress Hormones: Unveiling the Role in Accelerated Cellular Senescence.},
journal = {Aging and disease},
volume = {16},
number = {4},
pages = {1946-1970},
pmid = {39226159},
issn = {2152-5250},
mesh = {Humans ; *Cellular Senescence/physiology ; Oxidative Stress/physiology ; Animals ; Hypothalamo-Hypophyseal System/metabolism ; *Stress, Physiological/physiology ; Pituitary-Adrenal System/metabolism ; Aging ; },
abstract = {Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen species, and inducing oxidative stress, DNA damage, and inflammatory reactions, ultimately resulting in accelerated cellular senescence. The process of stress-induced cellular senescence has been implicated in a number of chronic diseases, including age-related macular degeneration, chronic kidney disease, type 2 diabetes, cardiovascular disease and obstructive sleep apnea. In this review, we integrate recent progress research progress in our understanding of the mechanisms of stress-induced cellular senescence and discuss its underlying mechanisms from the perspective of stress hormones. We review potential therapeutic targets for stress-induced premature senescence and discuss the advantages and limitations of existing pharmacological agents capable of ameliorating stress-induced premature senescence.},
}
@article {pmid39226064,
year = {2024},
author = {Kim, N and Lee, M and Chung, H and Kim, HC and Lee, H},
title = {Prediction of Post-Treatment Visual Acuity in Age-Related Macular Degeneration Patients With an Interpretable Machine Learning Method.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {9},
pages = {3},
pmid = {39226064},
issn = {2164-2591},
mesh = {Humans ; *Visual Acuity/physiology ; Female ; Male ; Aged ; *Tomography, Optical Coherence/methods ; *Machine Learning ; *Fluorescein Angiography/methods ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Wet Macular Degeneration/drug therapy/physiopathology/diagnostic imaging/diagnosis ; Indocyanine Green/administration &amp; dosage ; Intravitreal Injections ; ROC Curve ; Retrospective Studies ; Ranibizumab/therapeutic use/administration &amp; dosage ; Middle Aged ; },
abstract = {PURPOSE: We evaluated the features predicting visual acuity (VA) after one year in neovascular age-related macular degeneration (nAMD) patients.<br><br>METHODS: A total of 527 eyes of 506 patients were included. Machine learning (ML) models were trained to predict VA deterioration beyond a logarithm of the minimum angle of resolution of 1.0 after 1 year based on the sequential addition of multimodal data. BaseM models used clinical data (age, sex, treatment regimen, and VA), SegM models included fluid volumes from optical coherence tomography (OCT) images, and RawM models used probabilities of visual deterioration (hereafter probability) from deep learning classifiers trained on baseline OCT (OCT0) and OCT after three loading doses (OCT3), fluorescein angiography, and indocyanine green angiography. We applied SHapley Additive exPlanations (SHAP) for machine learning model interpretation.<br><br>RESULTS: The RawM model based on the probability of OCT0 outperformed the SegM model (area under the receiver operating characteristic curve of 0.95 vs. 0.91). Adding probabilities from OCT3, fluorescein angiography, and indocyanine green angiography to RawM showed minimal performance improvement, highlighting the practicality of using raw OCT0 data for predicting visual outcomes. Applied SHapley Additive exPlanations analysis identified VA after 3 months and OCT3 probability values as the most influential features over quantified fluid segments.<br><br>CONCLUSIONS: Integrating multimodal data to create a visual predictive model yielded accurate, interpretable predictions. This approach allowed the identification of crucial factors for predicting VA in patients with nAMD.<br><br>TRANSLATIONAL RELEVANCE: Interpreting a predictive model for 1-year VA in patients with nAMD from multimodal data allowed us to identify crucial factors for predicting VA.},
}
@article {pmid39225974,
year = {2024},
author = {Pablo, L and Garay-Aramburu, G and García Layana, A and Fernandez, A and Vázquez, I and Acebes, X and Zulueta, J and Balonga, D and Salinas-Ortega, L and Muñoz, &#xc1; and Casado Gómez, A and Casado, M&#xc1; and Salvador, J and Bañón-Rodriguez, I and Ruíz-Moreno, JM},
title = {Assessing the economic burden of vision loss and irreversible legal blindness in Spain (2021-2030): a societal perspective.},
journal = {Health economics review},
volume = {14},
number = {1},
pages = {70},
pmid = {39225974},
issn = {2191-1991},
abstract = {OBJECTIVE: To estimate the economic impact for the society, generated as a consequence of the onset of loss of vision and irreversible legal blindness, for the main ophthalmologic diseases in Spain: glaucoma, diabetic retinopathy (DR), diabetic macular edema (DME), age-related macular degeneration (AMD) and high myopia (HM).<br><br>METHODS: A cost analysis model was developed to estimate the economic burden of glaucoma, DR, DME, AMD and HM over a 10-year time horizon (2021-2030), from a societal perspective in Spain. The epidemiological and economic parameters used in the model were obtained through a literature review. Prevalence, incidence, and progression stages were used to establish the epidemiological flows. Annual costs per patient from publications were included and classified into direct healthcare, direct non-healthcare and indirect costs. Costs from other countries were converted based on purchasing-power-parity (&#x20ac;EUR, PPP). Epidemiological parameters about population and cost results were validated by a panel of experts. All costs were adjusted to euros, 2021 (&#x20ac;, 2021), and using the Consumer Price Index (CPI) of the last 10 years, extrapolated to 2030 euros (&#x20ac;, 2030).<br><br>RESULTS: It was estimated that the total population of patients with the main diseases pathologies (glaucoma, DR, DME, AMD and HM) will increase to 7.99 million patients by 2030, representing an increase of 103%. The total cost by 2030 of all pathologies would amount to 99.8 billion euros. Direct non-healthcare costs account for the largest item (44%), followed by loss of productivity costs (38%), and direct healthcare costs (18%). The pathologies with the highest cumulative costs will be glaucoma (&#x20ac;33.6 billion) and DME (&#x20ac;19.8 billion).The greatest increment costs compared to 2021 will likely be generated by pathologies related to diabetes mellitus, such as DR (703%) and DME (317%).<br><br>CONCLUSIONS: Knowing the costs associated with the pathologies that generate loss of vision and irreversible legal blindness is essential to understand the socioeconomic impact associated with these pathologies. Furthermore, the high cost of treating these diseases makes necessary to coordinate efforts between administrations, together with the support of patient associations, to meet their needs.},
}
@article {pmid39224530,
year = {2024},
author = {Moraes, G and Struyven, R and Wagner, SK and Liu, T and Chong, D and Abbas, A and Chopra, R and Patel, PJ and Balaskas, K and Keenan, TDL and Keane, PA},
title = {Quantifying Changes on OCT in Eyes Receiving Treatment for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100570},
pmid = {39224530},
issn = {2666-9145},
support = {MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {PURPOSE: Application of artificial intelligence (AI) to macular OCT scans to segment and quantify volumetric change in anatomical and pathological features during intravitreal treatment for neovascular age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database.<br><br>PARTICIPANTS: A total of 2115 eyes from 1801 patients starting anti-VEGF treatment between June 1, 2012, and June&#xa0;30, 2017.<br><br>METHODS: The Moorfields Eye Hospital neovascular AMD database was queried for first and second eyes receiving anti-VEGF treatment and had an OCT scan at baseline and 12 months. Follow-up scans were input into the AI system and volumes of OCT variables were studied at different time points and compared with baseline volume groups. Cross-sectional comparisons between time points were conducted using Mann-Whitney U test.<br><br>MAIN OUTCOME MEASURES: Volume outputs of the following variables were studied: intraretinal fluid, subretinal fluid, pigment epithelial detachment (PED), subretinal hyperreflective material (SHRM), hyperreflective foci, neurosensory retina, and retinal pigment epithelium.<br><br>RESULTS: Mean volumes of analyzed features decreased significantly from baseline to both 4 and 12 months, in both first-treated and second-treated eyes. Pathological features that reflect exudation, including pure fluid components (intraretinal fluid and subretinal fluid) and those with fluid and fibrovascular tissue (PED and SHRM), displayed similar responses to treatment over 12 months. Mean PED and SHRM volumes showed less pronounced but also substantial decreases over the first 2 months, reaching a plateau postloading phase, and minimal change to 12 months. Both neurosensory retina and retinal pigment epithelium volumes showed gradual reductions over time, and were not as substantial as exudative features.<br><br>CONCLUSIONS: We report the results of a quantitative analysis of change in retinal segmented features over time, enabled by an AI segmentation system. Cross-sectional analysis at multiple time points demonstrated significant associations between baseline OCT-derived segmented features and the volume of biomarkers at follow-up. Demonstrating how certain OCT biomarkers progress with treatment and the impact of pretreatment retinal morphology on different structural volumes may provide novel insights into disease mechanisms and aid the personalization of care. Data will be made public for future studies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39223298,
year = {2024},
author = {Ma, X and Wu, W and Hara, M and Zhou, J and Panzarin, C and Schafer, CM and Griffin, CT and Cai, J and Ma, JX and Takahashi, Y},
title = {Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration.},
journal = {Communications biology},
volume = {7},
number = {1},
pages = {1075},
pmid = {39223298},
issn = {2399-3642},
support = {EY033330//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY034742/EY/NEI NIH HHS/United States ; EY019309//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; EY034510//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY028949/EY/NEI NIH HHS/United States ; EY034742//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; EY032930//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY032931/EY/NEI NIH HHS/United States ; R01 EY032930/EY/NEI NIH HHS/United States ; R01 EY028773/EY/NEI NIH HHS/United States ; R01 EY033477/EY/NEI NIH HHS/United States ; EY033477//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY034510/EY/NEI NIH HHS/United States ; EY028949//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY033330/EY/NEI NIH HHS/United States ; EY032931//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; R01 EY019309/EY/NEI NIH HHS/United States ; EY028773//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology ; Animals ; *Macular Degeneration/metabolism/pathology/genetics ; Mice ; *Mitochondria/metabolism/pathology ; *Fibrosis ; *Carnitine O-Palmitoyltransferase/metabolism/genetics/deficiency ; *Transforming Growth Factor beta2/metabolism/genetics ; *Receptors, LDL/metabolism/genetics/deficiency ; Humans ; Mice, Knockout ; Epithelial-Mesenchymal Transition ; Energy Metabolism ; Mice, Inbred C57BL ; },
abstract = {Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr[-/-] mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFβ2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFβ receptor I/II complex by interacting with unglycosylated TGFβ receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFβ2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.},
}
@article {pmid39222802,
year = {2025},
author = {Sheth, JU and Stewart, MW and Narayanan, R and Anantharaman, G and Chandran, K and Lai, TYY and Chakravarthy, U and Das, T},
title = {Macular neovascularization.},
journal = {Survey of ophthalmology},
volume = {70},
number = {4},
pages = {653-675},
doi = {10.1016/j.survophthal.2024.08.003},
pmid = {39222802},
issn = {1879-3304},
mesh = {Humans ; Tomography, Optical Coherence ; Angiogenesis Inhibitors/therapeutic use ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Retinal Neovascularization/diagnosis/therapy/etiology ; *Macula Lutea/blood supply/pathology ; *Choroidal Neovascularization/diagnosis/therapy ; },
abstract = {Neovascularization of the macula, a common complication of many chorioretinal diseases such as neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and pathologic myopia, results from increased synthesis of vascular endothelial growth factor (VEGF) by the retinal pigment epithelium and/or Müller cells because of localized ischemia and inflammation. The Consensus on Neovascular AMD Nomenclature (CONAN) study group acknowledged that these vessels may originate from either the choriocapillaris or the retinal microvasculature, prompting them to propose the term 'macular neovascularization' (MNV) to include intraretinal, subretinal, and sub-pigment epithelial neovascularization localized to the macula. MNV frequently appears as a grey-green macular lesion with overlying intraretinal thickening and/or subretinal exudation, causing metamorphopsia, reduced central vision, relative central scotoma, decreased reading speed, and problems with color recognition. Multimodal imaging with optical coherence tomography (OCT), OCT angiography, dye-based angiographies, fundus autofluorescence, and multiwavelength photography help establish the diagnosis and aid in selecting an appropriate treatment. The standard of care for MNV is usually intravitreal anti-vascular endothelial growth factor injections, though thermal laser photocoagulation, verteporfin photodynamic therapy, and vitreoretinal surgery are occasionally used. We discuss the etiology and clinical features of MNV, the role of multimodal imaging in establishing the diagnosis, and the available therapeutic options.},
}
@article {pmid39221933,
year = {2024},
author = {Zhang, Q and Shu, DY and Bryan, RA and Han, JYS and Gulette, GA and Lo, K and Kim, LA and Miller, JML},
title = {Long-term Monitoring of Oxygen Consumption Rates in Highly Differentiated and Polarized Retinal Pigment Epithelial Cultures.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {210},
pages = {},
pmid = {39221933},
issn = {1940-087X},
support = {K08 EY033420/EY/NEI NIH HHS/United States ; P30 EY007003/EY/NEI NIH HHS/United States ; R01 EY027739/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; Humans ; *Oxygen Consumption/physiology ; Cell Culture Techniques/methods ; Cell Differentiation/physiology ; },
abstract = {Mitochondrial metabolism is critical for the normal function of the retinal pigment epithelium (RPE), a monolayer of cells in the retina important for photoreceptor survival. RPE mitochondrial dysfunction is a hallmark of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the developed world, and proliferative vitreoretinopathy (PVR), a blinding complication of retinal detachments. RPE degenerative conditions have been well-modeled by RPE culture systems that are highly differentiated and polarized to mimic in vivo RPE. However, monitoring oxygen consumption rates (OCR), a proxy for mitochondrial function, has been difficult in such culture systems because the conditions that promote ideal RPE polarization and differentiation do not allow for easy OCR measurements. Here, we introduce a novel system, Resipher, to monitor OCR for weeks at a time in well-differentiated RPE cultures while maintaining the RPE on optimal growth substrates and physiologic culture media in a standard cell culture incubator. This system calculates OCR by measuring the oxygen concentration gradient present in the media above cells. We discuss the advantages of this system over other methods for detecting OCR and how to set up the system for measuring OCR in RPE cultures. We cover key tips and tricks for using the system, caution about interpreting the data, and guidelines for troubleshooting unexpected results. We also provide an online calculator for extrapolating the level of hypoxia, normoxia, or hyperoxia RPE cultures experience based on the oxygen gradient in the media above cells detected by the system. Finally, we review two applications of the system, measuring the metabolic state of RPE cells in a PVR model and understanding how the RPE metabolically adapts to hypoxia. We anticipate that the use of this system on highly polarized and differentiated RPE cultures will enhance our understanding of RPE mitochondrial metabolism both under physiologic and disease states.},
}
@article {pmid39218386,
year = {2025},
author = {Berni, A and Oakley, JD and Dolz-Marco, R and Gallego-Pinazo, R and Cimorosi, F and Ghilardi, A and Russakoff, DB and Barresi, C and Introini, U and Reibaldi, M and Bandello, F and Borrelli, E},
title = {Topographical Quantification of Retinal Fluid in Type 3 MNV and Associations With Short-Term Visual Outcomes.},
journal = {American journal of ophthalmology},
volume = {269},
number = {},
pages = {181-188},
doi = {10.1016/j.ajo.2024.08.024},
pmid = {39218386},
issn = {1879-1891},
mesh = {Humans ; *Visual Acuity/physiology ; *Subretinal Fluid ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Bevacizumab/therapeutic use ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Follow-Up Studies ; },
abstract = {PURPOSE: This study aims to quantify the volume of intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (sub-RPE) fluid in treatment-naïve Type 3 macular neovascularization (MNV) eyes with age-related macular degeneration (AMD) and to investigate the correlation of these fluid volumes with visual acuity (VA) outcomes at baseline and following antivascular endothelial growth factor (VEGF) treatment.<br><br>DESIGN: Retrospective, clinical cohort study.<br><br>METHODS: In this study, we analyzed patients diagnosed with exudative AMD and treatment-na&#xef;ve Type 3 MNV undergoing a loading dose of anti-VEGF therapy. Using a validated deep-learning segmentation strategy, we processed optical coherence tomography (OCT) B-scans to segment and quantify IRF (i.e., both in the inner and outer retina), SRF, and sub-RPE fluid volumes at baseline. The study correlated baseline fluid volumes with baseline and short-term VA outcomes postloading dose of anti-VEGF injections.<br><br>RESULTS: Forty-six eyes from 46 patients were included in this study. Visual acuity was 0.51 &#xb1; 0.30 LogMAR at baseline and 0.33 &#xb1; 0.20 LogMAR after the loading dose of anti-VEGF (P = .001). Visual acuity at the follow-up visit was 0.40 &#xb1; 0.17 LogMAR in patients with no complete resolution of retinal fluid and 0.31 &#xb1; 0.20 LogMAR in eyes without retinal fluid after treatment (P = .225). In the multivariable analysis, the IRF volume in the inner retina (P = .032) and the distance of the MNV from the fovea (P = .037) were predictors of visual acuity at baseline. The baseline IRF volume in the inner retina also predicted the visual acuity at follow-up (P = .023).<br><br>CONCLUSION: The present study highlights the fluid volume in the inner retina as a crucial predictor of short-term visual outcomes in Type 3 MNV, underscoring the detrimental effect of IRF on neuroretinal structures.},
}
@article {pmid39218384,
year = {2025},
author = {Lee, MY and Han, K and Min, KH and Yu, DS and Lee, YB},
title = {Psoriasis as a Predictor of Neovascular Age-Related Macular Degeneration in Type 2 Diabetes Mellitus: A Nationwide Cohort Study.},
journal = {American journal of ophthalmology},
volume = {269},
number = {},
pages = {236-245},
doi = {10.1016/j.ajo.2024.08.033},
pmid = {39218384},
issn = {1879-1891},
mesh = {Humans ; *Diabetes Mellitus, Type 2/epidemiology/complications ; *Psoriasis/epidemiology/complications ; Male ; Female ; Retrospective Studies ; Incidence ; Middle Aged ; Aged ; Risk Factors ; Wet Macular Degeneration/epidemiology/diagnosis ; Adult ; Proportional Hazards Models ; Republic of Korea/epidemiology ; Taiwan/epidemiology ; Follow-Up Studies ; },
abstract = {PURPOSE: The objective of this study is to evaluate the relationship of psoriasis and neovascular age-related macular degeneration (nAMD) in a population with diabetic mellitus (DM).<br><br>DESIGN: Nationwide, population-based, retrospective cohort study.<br><br>METHODS: Records of patients over 40 years of age who had been diagnosed with type 2 diabetes mellitus from January 2009 to December 2012 were analyzed. The incidence of nAMD was observed from the index year to December 2018 in all subjects. The incidence rate of nAMD was compared between the psoriasis group and control group. Covariates include age, sex, body mass index, income level, smoking status, drinking status, regular exercise habits, hypertension, dyslipidemia, end-stage renal disease, diabetic retinopathy, glucose level, prescription of more than 3 oral hypoglycemic agents, and a history of diabetes mellitus exceeding 5 years.<br><br>RESULTS: Of 2,245,358 patients with type 2 DM, 20,853 patients were classified in the psoriasis group and the other 2,224,505 in the control group. A total of 105 nAMD cases were observed in the psoriasis group and 7459 cases in the control group. According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly higher risk for nAMD compared to controls (hazard ratio = 1.329, 95% CI = 1.096-1.612) after adjustments for covariates.<br><br>CONCLUSIONS: This study demonstrated that psoriasis was an independent risk factor for developing nAMD in DM patients. Therefore, physicians should be alert to the development of nAMD in DM patients who also have psoriasis.},
}
@article {pmid39217583,
year = {2024},
author = {Li, X and Piao, J and Kang, B and Eom, Y and Kim, DH and Song, JS},
title = {The toxic effects of polystyrene microplastic/nanoplastic particles on retinal pigment epithelial cells and retinal tissue.},
journal = {Environmental science and pollution research international},
volume = {31},
number = {42},
pages = {54950-54961},
pmid = {39217583},
issn = {1614-7499},
mesh = {*Retinal Pigment Epithelium/drug effects ; *Polystyrenes/toxicity ; Rats ; Humans ; *Microplastics/toxicity ; *Oxidative Stress/drug effects ; *Retina/drug effects ; Animals ; Cell Survival/drug effects ; Epithelial Cells/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {The increasing use of contact lenses, artificial tears, and anti-vascular endothelial growth factor (anti-VEGF) drug injections for age-related macular degeneration has heightened the likelihood of eye exposure to microplastic particles. Extensive research has established that microplastic particles can induce oxidative stress on the ocular surface, resulting in damage. However, the impact of these particles on the retina remains unclear. Therefore, this study investigated whether microplastics/nanoplastics (MPs/NPs) cause retinal damage. In vitro human retinal pigment epithelial (RPE) cells were exposed to polystyrene MPs and NPs for 48 h. Assessment of cell viability using WST-8; evaluation of TNF-α and IL-1β expression; observation of cell morphology and particle invasion via TEM; measurement of ROS levels using the DCFDA reagent; and western blot analysis of SOD2, FIS1, Drp1, and LC3B expression were conducted. In vivo experiments involved intravitreal injection of MPs/NPs in rats, followed by retinal H&amp;E staining 24 h later and evaluation of TNF-α and IL-1β expression. Results indicated that exposure to MPs did not significantly alter RPE cell viability, whereas exposure to NPs led to a noticeable decrease. TEM images revealed NPs' penetration into cells, causing increased oxidative stress (SOD2), mitochondrial fission (FIS1, Drp1), and mitochondrial autophagy (LC3B). In vivo experiments demonstrated an increase in inflammatory cells in retinal tissues exposed to NPs, along with elevated levels of TNF-α and IL-1β. Conclusively, both MPs and NPs impact the retina, with NPs displaying greater toxicity. NPs significantly elevate ROS levels in the retina and induce mitochondrial fission and mitophagy in RPE cells compared to MPs.},
}
@article {pmid39216841,
year = {2024},
author = {Bresciani, G and Manai, F and Felszeghy, S and Smedowski, A and Kaarniranta, K and Amadio, M},
title = {VEGF and ELAVL1/HuR protein levels are increased in dry and wet AMD patients. A new tile in the pathophysiologic mechanisms underlying RPE degeneration?.},
journal = {Pharmacological research},
volume = {208},
number = {},
pages = {107380},
doi = {10.1016/j.phrs.2024.107380},
pmid = {39216841},
issn = {1096-1186},
mesh = {Aged ; Aged, 80 and over ; Animals ; Female ; Humans ; Male ; Mice ; Middle Aged ; *ELAV-Like Protein 1/metabolism/genetics ; Geographic Atrophy/metabolism ; Macular Degeneration/metabolism/physiopathology/pathology ; Mice, Inbred C57BL ; Mice, Knockout ; *NF-E2-Related Factor 2/metabolism/genetics ; Oxidative Stress ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism ; *Vascular Endothelial Growth Factor A/metabolism ; Wet Macular Degeneration/metabolism/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a common retinal pathology characterized by degeneration of macula's retinal pigment epithelium (RPE) and photoreceptors, visual impairment, or loss. Compared to wet AMD, dry AMD is more common, but lacks cures; therefore, identification of new potential therapeutic targets and treatments is urgent. Increased oxidative stress and declining antioxidant, detoxifying systems contribute to the pathophysiologic mechanisms underlying AMD. The present work shows that the Embryonic Lethal Abnormal Vision-Like 1/Human antigen R (ELAVL1/HuR) and the Vascular Endothelial Growth Factor (VEGF) protein levels are higher in the RPE of both dry and wet AMD patients compared to healthy subjects. Moreover, increased HuR protein levels are detected in the retina, and especially in the RPE layer, of a dry AMD model, the nuclear factor erythroid 2-related factor 2 (Nrf2) / peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) double knock-out mouse. The crosstalk among Nrf2, HuR and VEGF has been also studied in ARPE-19 cells in basal and stressful conditions related to the AMD context (i.e., oxidative stress, autophagy impairment, Nrf2 deficit), offering new evidence of the mutual influence between Nrf2 and HuR, of the dependence of VEGF expression and secretion by these two factors, and of the increased susceptibility of cells to stressful conditions in Nrf2- or HuR-impaired contexts. Overall, this study shows evidence of the interplay among Nrf2, HuR and VEGF, essential factors for RPE homeostasis, and represents an additional piece in the understanding of the complex pathophysiologic mechanisms underlying AMD.},
}
@article {pmid39216728,
year = {2025},
author = {Borrelli, E and Olivieri, C and Serafino, S and Coletto, A and Ricardi, F and Neri, G and Marolo, P and Reibaldi, M},
title = {Interreader and Intermodality Variability in Macular Atrophy Quantification in Neovascular Age-related Macular Degeneration: Comparison of 6 Imaging Modalities.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {3},
pages = {212-223},
doi = {10.1016/j.oret.2024.08.017},
pmid = {39216728},
issn = {2468-6530},
mesh = {Humans ; Female ; Male ; *Tomography, Optical Coherence/methods ; Prospective Studies ; Aged ; *Wet Macular Degeneration/diagnosis/complications ; *Fluorescein Angiography/methods ; *Macula Lutea/pathology ; Fundus Oculi ; Aged, 80 and over ; Reproducibility of Results ; Follow-Up Studies ; Visual Acuity ; Atrophy ; Middle Aged ; },
abstract = {PURPOSE: Macular atrophy is a common complication in neovascular age-related macular degeneration (AMD) and is associated with poorer visual outcomes. This study evaluated interreader and intermodality variability in measuring macular atrophy in previously treated neovascular AMD eyes without exudation using 6 imaging modalities.<br><br>DESIGN: Prospective, cohort study.<br><br>PARTICIPANTS: Thirty participants with previously treated neovascular AMD showing no signs of exudation at the time of enrollment and exhibiting macular atrophy.<br><br>METHODS: During the same clinic visit, patients were imaged using 6 different imaging modalities: color fundus photography (CFP; Clarus, Carl Zeiss Meditec), near-infrared imaging (NIR; Spectralis, Heidelberg Engineering), structural OCT (Spectralis, Heidelberg Engineering), green fundus autofluorescence (GAF; Clarus, Carl Zeiss Meditec), blue fundus autofluorescence (BAF; Spectralis, Heidelberg Engineering), and pseudocolor imaging (MultiColor; Spectralis, Heidelberg Engineering). Two readers independently measured the macular atrophy area.<br><br>MAIN OUTCOME MEASURES: Interreader and intermodality agreement.<br><br>RESULTS: The 95% coefficient of repeatability was 5.98 mm[2] for CFP, 4.46 mm[2] for MultiColor, 3.90 mm[2] for BAF, 3.92 mm[2] for GAF, 4.86 mm[2] for NIR, and 3.55 mm[2] for OCT. Similarly, the coefficient of variation was lowest for OCT-based grading at 0.08 and highest for NIR-based grading at 0.28. Accordingly, the intraclass correlation coefficient was 0.742 for CFP, 0.805 for MultiColor, 0.857 for BAF, 0.850 for GAF, 0.755 for NIR, and 0.917 for OCT. The 6 different imaging modalities presented measurements with different mean values, with only a limited number of comparisons not significantly different between the instruments, although measurements were correlated. The largest size of macular atrophy was measured with structural OCT-based grading (median&#xa0;= 4.65 mm[2]; interquartile range [IQR]&#xa0;= 4.78 mm[2]) and the smallest was with CFP-based grading (median&#xa0;= 3.86 mm[2]; IQR&#xa0;= 5.06 mm[2]). Inconsistencies arose from various factors.<br><br>CONCLUSIONS: In patients with neovascular AMD, macular atrophy measurements vary significantly depending on the imaging technique used. Color fundus photography-based assessments yielded the smallest macular atrophy sizes, whereas structural OCT-based assessments produced the largest. These discrepancies stem from both the inherent limitations of each modality in assessing retinal pigment epithelial atrophy and factors related to neovascularization, such as the coexistence of fibrosis.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39215883,
year = {2024},
author = {Sajiki, AF and Kataoka, K and Takeuchi, J and Ota, H and Nakano, Y and Horiguchi, E and Kaneko, H and Terasaki, H and Ito, Y and Nishiguchi, KM},
title = {Clinical utility of swept-source optical coherence tomography angiography for the diagnosis of exudative maculopathy.},
journal = {Japanese journal of ophthalmology},
volume = {68},
number = {6},
pages = {614-620},
pmid = {39215883},
issn = {1613-2246},
support = {22K20958//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; *Fluorescein Angiography/methods ; Female ; Aged ; Middle Aged ; *Fundus Oculi ; Wet Macular Degeneration/diagnosis ; Reproducibility of Results ; Central Serous Chorioretinopathy/diagnosis ; Diagnosis, Differential ; Aged, 80 and over ; Macula Lutea/diagnostic imaging ; Visual Acuity ; },
abstract = {PURPOSE: To assess the feasibility of swept-source optical coherence tomography angiography (SS-OCTA) to differentiate macular diseases, including nonpolypoidal macular neovascularization (MNV), polypoidal choroidal vasculopathy (PCV), type 3 MNV, and chronic central serous chorioretinopathy (CSC) without indocyanine green angiography (ICGA).<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: This study examined 63 eyes of 63 patients with treatment-naive neovascular age-related macular degeneration&#xa0;(AMD), including 23 eyes with nonpolypoidal MNV, 17 eyes with PCV, and 1 eye with type 3 MNV and 22 eyes with chronic CSC. Two independent retina specialists, blinded to the clinical diagnosis, assessed each case of neovascular AMD and chronic CSC using only B-scan and en face images of SS-OCTA without referring to other examination outcomes.<br><br>RESULTS: By SS-OCTA alone, 19 eyes were diagnosed with nonpolypoidal MNV, 17 eyes with PCV, 2 eyes with type 3 MNV, and 22 eyes with chronic CSC, indicating high sensitivity (82.6%, 94.1%, 100%, and 100%, respectively) and specificity (100%, 97.8%, 98.4%, and 100%, respectively); however, three eyes could not be diagnosed because of obscure images. The agreement of diagnosis with SS-OCTA alone was high between the two specialists (&#x3ba;&#x2009;=&#x2009;0.82).<br><br>CONCLUSION: SS-OCTA showed high sensitivity and specificity in the differentiation of nonpolypoidal MNV, PCV, type 3 MNV, and chronic CSC. The differential criteria based on SS-OCTA could be a substitute for the ICGA-based diagnoses.},
}
@article {pmid39215566,
year = {2024},
author = {Yang, F and Ma, H and Boye, SL and Boye, SE and Ding, XQ},
title = {Promotion of endoplasmic reticulum retrotranslocation by overexpression of E3 ubiquitin-protein ligase synoviolin 1 reduces endoplasmic reticulum stress and preserves cone photoreceptors in cyclic nucleotide-gated channel deficiency.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {38},
number = {17},
pages = {e70021},
pmid = {39215566},
issn = {1530-6860},
support = {5P30GM122744/GF/NIH HHS/United States ; R01 EY033841/EY/NEI NIH HHS/United States ; R01EY024280/GF/NIH HHS/United States ; R01 EY027754/EY/NEI NIH HHS/United States ; P30 GM122744/GM/NIGMS NIH HHS/United States ; P30 EY021725/EY/NEI NIH HHS/United States ; P30EY021725/GF/NIH HHS/United States ; R01EY027754/GF/NIH HHS/United States ; R01EY033841/GF/NIH HHS/United States ; R01 EY024280/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Ubiquitin-Protein Ligases/genetics/metabolism ; *Retinal Cone Photoreceptor Cells/metabolism/pathology ; Mice ; *Endoplasmic Reticulum/metabolism ; *Endoplasmic Reticulum Stress ; *Cyclic Nucleotide-Gated Cation Channels/genetics/metabolism ; Endoplasmic Reticulum-Associated Degradation ; Mice, Knockout ; Mice, Inbred C57BL ; },
abstract = {Cone photoreceptor cyclic nucleotide-gated (CNG) channels play an essential role in phototransduction and cellular Ca[2+] homeostasis. Mutations in genes encoding the channel subunits CNGA3 and CNGB3 are associated with achromatopsia, progressive cone dystrophy, and early-onset macular degeneration. Cone loss in patients with achromatopsia and cone dystrophy associated with CNG channel mutations has been documented by optical coherence tomography and in mouse models of CNG channel deficiency. Cone death in CNG channel-deficient retinas involves endoplasmic reticulum (ER) stress-associated apoptosis, dysregulation of cellular/ER Ca[2+] homeostasis, impaired protein folding/processing, and impaired ER-associated degradation (ERAD). The E3 ubiquitin-protein ligase synoviolin 1 (SYVN1) is the primary component of the SYVN1/SEL1L ER retrotranslocon responsible for ERAD. Previous studies have shown that manipulations that protect cones and reduce ER stress/cone death in CNG channel deficiency, such as increasing ER Ca[2+] preservation or treatment with an ER chaperone, increase the expression of SYVN1 and other components of the ER retrotranslocon. The present work investigated the effects of SYVN1 overexpression. Intraocular injection of AAV5-IRBP/GNAT2-Syvn1 resulted in overexpression of SYVN1 in cones of CNG channel-deficient mice. Following treatment, cone density in Cnga3[-/-] mice was significantly increased, compared with untreated controls, outer segment localization of cone opsin was improved, and ER stress/apoptotic cell death was reduced. Overexpression of SYVN1 also led to increased expression levels of the retrotranslocon components, degradation in ER protein 1 (DERL1), ERAD E3 ligase adaptor subunit (SEL1L), and homocysteine inducible ER protein with ubiquitin-like domain 1 (HERPUD1). Moreover, overexpression of SYVN1 likely enhanced protein ubiquitination/proteasome degradation in CNG channel-deficient retinas. This study demonstrates the role of SYVN1/ERAD in cone preservation in CNG channel deficiency and supports the strategy of promoting ERAD for cone protection.},
}
@article {pmid39215141,
year = {2024},
author = {Downey, L and Sivaprasad, S and Chhabra, R and Bailey, C and Chakrabarti, S and Elsherbiny, S and Patel, J and Silvestri, G and Watson, SL and Williams, G and Parker, A and Khokhar, S and Lotery, A},
title = {Dual pathway inhibition with faricimab for previously treated neovascular age-related macular degeneration and diabetic macular oedema: guidance from a UK panel of retina specialists.},
journal = {Eye (London, England)},
volume = {38},
number = {16},
pages = {3077-3086},
pmid = {39215141},
issn = {1476-5454},
mesh = {Humans ; *Diabetic Retinopathy/drug therapy/diagnosis ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Macular Edema/drug therapy ; *Intravitreal Injections ; United Kingdom ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/physiopathology ; Visual Acuity/physiology ; Angiopoietin-2/antagonists &amp; inhibitors ; },
abstract = {BACKGROUND/OBJECTIVES: Some eyes with neovascular age-related macular degeneration (nAMD) and centre-involving diabetic macular oedema (DMO) fail to respond sufficiently or lose response over time to standard of care intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. This paper explores clinical scenarios for switching to dual action angiopoietin-2 (Ang-2)/VEGF-A inhibitor faricimab (Vabysmo, Roche Products Limited) in previously anti-VEGF-treated patients.<br><br>METHODS: A national steering group meeting of UK retina specialists was held in London on 27 October 2023. Clinician practice and experience were reviewed together with pivotal clinical trial data and early findings from real-world settings. Roche Products Limited facilitated and funded the meeting.<br><br>RESULTS: While there is no standardised protocol for identifying suboptimal response, the authors review relevant clinical biomarkers of disease activity used in routine clinical practice to determine patient response and guide treatment decisions. Common reasons identified for considering a change of treatment were lack of efficacy demonstrated by suboptimal anatomic or visual improvement and insufficient durability of response. The panel outline strategies for switching to faricimab among eligible patients with a prior anti-VEGF treatment history, with initial monthly loading doses or maintaining the previous treatment interval before attempting to extend, that may be integrated into current treat-and-extend (T&amp;E) clinical pathways for treating patients with nAMD and DMO. General considerations for switching between treatments are also reviewed.<br><br>CONCLUSION: Clinicians may consider a treatment switch to faricimab in nAMD and DMO patients who have suboptimal disease control or insufficient durability of response on initial anti-VEGF therapy.},
}
@article {pmid39214946,
year = {2024},
author = {Kim, J and Park, MS and Cho, BJ and Kwon, S},
title = {High-Dose Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration Resistant to Standard-Dose Brolucizumab.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {10},
pages = {2789-2797},
pmid = {39214946},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of escalating the dosage of intravitreal brolucizumab in patients with refractory neovascular age-related macular degeneration (AMD).<br><br>METHODS: This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12&#xa0;mg/0.1&#xa0;ml) for over 12&#xa0;months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6&#xa0;mg/0.05&#xa0;ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated.<br><br>RESULTS: Visual acuity was maintained from 68.3&#x2009;&#xb1;&#x2009;3.4 letters to 70.7&#x2009;&#xb1;&#x2009;3.2 letters after 12&#xa0;months of high-dose treatment (P&#x2009;=&#x2009;0.128). Central subfield thickness was 343.7&#x2009;&#xb1;&#x2009;17.0&#xa0;&#x3bc;m before high-dose treatment and 316.7&#x2009;&#xb1;&#x2009;18.5&#xa0;&#x3bc;m at 12&#xa0;months (P&#x2009;=&#x2009;0.083). The proportions of patients with subretinal fluid and serous pigment epithelial detachment significantly decreased from 82.4% to 41.2% and from 52.9% to 17.6%, respectively, after high-dose treatment (P&#x2009;=&#x2009;0.039 and P&#x2009;=&#x2009;0.031, respectively). The treatment interval extended from 7.2&#x2009;&#xb1;&#x2009;2.4&#xa0;weeks to 10.2&#x2009;&#xb1;&#x2009;2.2&#xa0;weeks after switching to standard-dose brolucizumab (P&#x2009;<&#x2009;0.001) and was maintained at 13.5&#x2009;&#xb1;&#x2009;2.8&#xa0;weeks after increasing the dose (P&#x2009;=&#x2009;0.154). No severe ocular adverse events were observed.<br><br>CONCLUSIONS: High-dose brolucizumab was effective in patients who did not respond to standard-dose brolucizumab after switching from previous anti-VEGF agents. Increasing the dosage could offer sustained disease control and reduce the treatment burden for patients with refractory AMD.},
}
@article {pmid39214343,
year = {2024},
author = {Zhang, XG and Yan, M and Huang, Z and Ye, Y and Deng, ZD and Song, YP},
title = {Quantitative assessment of choroidal parameters in type 1 macular neovascularization linked to central serous chorioretinopathy and neovascular age-related macular degeneration.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {49},
number = {},
pages = {104324},
doi = {10.1016/j.pdpdt.2024.104324},
pmid = {39214343},
issn = {1873-1597},
mesh = {Humans ; *Central Serous Chorioretinopathy ; Male ; Female ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; Middle Aged ; *Choroid/blood supply/diagnostic imaging/pathology ; Aged ; Macular Degeneration/complications ; Choroidal Neovascularization/diagnostic imaging ; Adult ; Fluorescein Angiography/methods ; Wet Macular Degeneration ; },
abstract = {OBJECTIVE: To use ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) to evaluate the choroidal features of neovascular age-related macular degeneration (nAMD) and type 1 macular neovascularization (MNV) attributable to central serous chorioretinopathy (CSC).<br><br>METHOD: A cross-sectional research was carried out to examine patients with type 1 MNV due to CSC (50 eyes) and nAMD (98 eyes) utilizing UWF SS-OCTA examinations. The scan procedure covered a vertical 20 mm &#xd7; horizontal 24 mm region with 9 subfields. A typical set of 68 healthy eyes was used for comparison. The effects of different diagnoses on choroidal parameters were assessed using covariance tests, using gender and age as variables.<br><br>RESULTS: The research showed that all choroidal characteristics were age-related (all p < 0.05). The calculated marginal averages of choroidal thickness (ChT) and choroidal volume (CV) in the central area were substantially lower in the nAMD group than in the CSC group and the normal group after age differences were taken into account (all p < 0.05). In both the superotemporal and temporal areas, the CSC group had a greater choroidal vascular index (CVI) compared to the nAMD group (p < 0.05). Additionally, the CSC group had a greater temporal area choriocapillaris density (CCD) than the nAMD group (p < 0.05).<br><br>CONCLUSION: At the choroidal level, type 1 MNV due to CSC and nAMD may be distinguished by UWF SS-OCTA. Compared to the nAMD affected eyes, the CSC affected eyes had increased ChT, CV, CVI, and CCD in several areas. The two diseases could be distinguished based on ChT and CV.},
}
@article {pmid39214250,
year = {2025},
author = {Sun, J and Song, Y and Gong, Y and Tao, L and Wang, H and Shu, X and Wen, Y and Cui, L and Ye, J and Lu, S and Deng, J and Li, H and Xu, Y and Qian, L and Wu, Z and Bi, Y and Liu, Q and Xu, X and Wu, M and Zhang, J and Hao, J and Tong, J and Dai, H and Wang, F and Zhao, M and Mao, J and Li, C and He, T and Pei, C and Liu, X and Wang, X and Li, M and Wang, W and Zheng, Q and Guan, H and Peng, H and Fan, K and Zhang, W and Zhu, D and Yu, S and Wei, W and Ding, L and Li, J and Lu, P and Yan, M and Liu, W and Jia, H and Sun, X},
title = {Efficacy and Safety of Efdamrofusp Alfa versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized, Double-Masked, Active-Controlled, Noninferiority, Phase II Trial.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {2},
pages = {156-165},
doi = {10.1016/j.oret.2024.08.014},
pmid = {39214250},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Dose-Response Relationship, Drug ; Double-Blind Method ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Randomized, double-masked, multicenter, active-controlled, noninferiority phase II study.<br><br>PARTICIPANTS: A total of 231 treatment-naive and previously treated participants with active choroidal neovascularization&#xa0;secondary to nAMD were enrolled.<br><br>METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa, or 2 mg aflibercept groups. Participants in all groups received 3 initial monthly loading doses, followed by treatment every 8 weeks, with assessment every 4 weeks up to week&#xa0;52.<br><br>MAIN OUTCOME MEASURES: The primary end point was the mean best-corrected visual acuity (BCVA) change from baseline to week 36. The prespecified noninferiority margin was set as -5 letters (80% confidence interval&#xa0;[CI]).<br><br>RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were&#xa0;+10.6,&#xa0;+11.4, and&#xa0;+12.0 letters, respectively; least squares mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups.<br><br>CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid39211129,
year = {2024},
author = {Chatterjee, S and Ghosh, S and Sin, Z and Davis, E and Preval, LV and Tran, N and Bammidi, S and Gautam, P and Hose, S and Sergeev, Y and Flores-Bellver, M and Aldiri, I and Sinha, D and Guha, P},
title = {βA3/A1-crystallin is an epigenetic regulator of histone deacetylase 3 (HDAC3) in the retinal pigmented epithelial (RPE) cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.08.06.606634},
pmid = {39211129},
issn = {2692-8205},
abstract = {The retinal pigmented epithelial (RPE) cells maintain retinal homeostasis, and alterations in their function contribute to non-exudative age-related macular degeneration (AMD) [1,2] . Here, we explore the intricate relationship between RPE cells, epigenetic modifications, and the development of AMD. Importantly, the study reveals a substantial decrease in histone deacetylase 3 (HDAC3) activity and elevated histone acetylation in the RPE of human AMD donor eyes. To investigate epigenetic mechanisms in AMD development, we used a mouse model with RPE-specific Cryba1 knockout [3-5] , revealing that the loss of βA3/A1-crystallin selectively reduces HDAC3 activity, resulting in increased histone acetylation. βA3/A1-crystallin activates HDAC3 by facilitating its interaction with the casein kinase II (CK2) and phosphorylating HDAC3, as well as by regulating intracellular InsP6 (phytic acid) levels, required for activating HDAC3. These findings highlight a novel function of βA3/A1-crystallin as an epigenetic regulator of HDAC3 in the RPE cells and provide insights into potential therapeutic strategies in non-exudative AMD.},
}
@article {pmid39211002,
year = {2024},
author = {Valter, K and Tedford, SE and Eells, JT and Tedford, CE},
title = {Photobiomodulation use in ophthalmology - an overview of translational research from bench to bedside.},
journal = {Frontiers in ophthalmology},
volume = {4},
number = {},
pages = {1388602},
pmid = {39211002},
issn = {2674-0826},
abstract = {Photobiomodulation (PBM) refers to the process in which wavelengths of light are absorbed by intracellular photoacceptors, resulting in the activation of signaling pathways that culminate in biological changes within the cell. PBM is the result of low-intensity light-induced reactions in the cell in contrast to thermal photoablation produced by high-intensity lasers. PBM has been effectively used in the clinic to enhance wound healing and mitigate pain and inflammation in musculoskeletal conditions, sports injury, and dental applications for many decades. In the past 20 years, experimental evidence has shown the benefit of PBM in increasing numbers of retinal and ophthalmic conditions. More recently, preclinical findings in ocular models have been translated to the clinic with promising results. This review discusses the preclinical and clinical evidence of the effects of PBM in ophthalmology and provides recommendations of the clinical use of PBM in the management of ocular conditions.},
}
@article {pmid39210705,
year = {2024},
author = {von der Burchard, C and Miura, Y and Stanzel, B and Chhablani, J and Roider, J and Framme, C and Brinkmann, R and Tode, J},
title = {Regenerative Retinal Laser and Light Therapies (RELITE): Proposal of a New Nomenclature, Categorization, and Trial Reporting Standard.},
journal = {Lasers in surgery and medicine},
volume = {56},
number = {8},
pages = {693-708},
doi = {10.1002/lsm.23833},
pmid = {39210705},
issn = {1096-9101},
support = {//The authors received no specific funding for this work./ ; },
mesh = {Humans ; Clinical Trials as Topic ; Laser Therapy/methods ; Phototherapy/methods ; Regeneration ; *Retinal Diseases/therapy ; *Terminology as Topic ; },
abstract = {OBJECTIVES: Numerous laser and light therapies have been developed to induce regenerative processes in the choroid/retinal pigment epithelium (RPE)/photoreceptor complex, leaving the neuroretina undamaged. These therapies are applied to the macula for the treatment of various diseases, most prominently diabetic maculopathy, retinal vein occlusion, central serous chorioretinopathy, and age-related macular degeneration. However, the abundance of technologies, treatment patterns, and dosimetry protocols has made understanding these therapies and comparing different approaches increasingly complex and challenging. To address this, we propose a new nomenclature system with a clear categorization that will allow for better understanding and comparability between different laser and light modalities. We propose this nomenclature system as an open standard that may be adapted in future toward new technical developments or medical advancements.<br><br>METHODS: A systematic literature review of reported macular laser and light therapies was conducted. A categorization into a standardized system was proposed and discussed among experts and professionals in the field. This paper does not aim to assess, compare, or evaluate the efficacy of different laser or dosimetry techniques or treatment patterns.<br><br>RESULTS: The literature search yielded 194 papers describing laser techniques, 50 studies describing dosimetry, 272 studies with relevant clinical trials, and 82 reviews. Following the common therapeutic aim, we propose "regenerative retinal laser and light therapies (RELITE)" as the general header. We subdivided RELITE into four main categories that refer to the intended physical and biochemical effects of temperature increase (photothermal therapy, PTT), RPE regeneration (photomicrodisruption therapy, PMT), photochemical processes (photochemical therapy, PCT), and photobiomodulation (photobiomodulation therapy, PBT). Further, we categorized the different dosimetry approaches and treatment regimens. We propose the following nomenclature system that integrates the most important parameters to enable understanding and comparability: Pattern-Dosimetry-Exposure Time/Frequency, Duty Cycle/Irradiation Diameter/Wavelength-Subcategory-Category.<br><br>CONCLUSION: Regenerative retinal laser and light therapies are widely used for different diseases and may become valuable in the future. A precise nomenclature system and strict reporting standards are needed to allow for a better understanding, reproduceable and comparable clinical trials, and overall acceptance. We defined categories for a systematic therapeutic goal-based nomenclature to facilitate future research in this field.},
}
@article {pmid39209215,
year = {2024},
author = {Lim, JI and Rachitskaya, AV and Hallak, JA and Gholami, S and Alam, MN},
title = {Artificial intelligence for retinal diseases.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {4},
pages = {100096},
doi = {10.1016/j.apjo.2024.100096},
pmid = {39209215},
issn = {2162-0989},
mesh = {*Artificial Intelligence ; *Retinal Diseases/diagnostic imaging/therapy ; *Mass Screening/methods ; Biomarkers/analysis ; Disease Progression ; Humans ; *Image Interpretation, Computer-Assisted/methods/standards ; Retina/diagnostic imaging ; },
abstract = {PURPOSE: To discuss the worldwide applications and potential impact of artificial intelligence (AI) for the diagnosis, management and analysis of treatment outcomes of common retinal diseases.<br><br>METHODS: We performed an online literature review, using PubMed Central (PMC), of AI applications to evaluate and manage retinal diseases. Search terms included AI for screening, diagnosis, monitoring, management, and treatment outcomes for age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal surgery, retinal vascular disease, retinopathy of prematurity (ROP) and sickle cell retinopathy (SCR). Additional search terms included AI and color fundus photographs, optical coherence tomography (OCT), and OCT angiography (OCTA). We included original research articles and review articles.<br><br>RESULTS: Research studies have investigated and shown the utility of AI for screening for diseases such as DR, AMD, ROP, and SCR. Research studies using validated and labeled datasets confirmed AI algorithms could predict disease progression and response to treatment. Studies showed AI facilitated rapid and quantitative interpretation of retinal biomarkers seen on OCT and OCTA imaging. Research articles suggest AI may be useful for planning and performing robotic surgery. Studies suggest AI holds the potential to help lessen the impact of socioeconomic disparities on the outcomes of retinal diseases.<br><br>CONCLUSIONS: AI applications for retinal diseases can assist the clinician, not only by disease screening and monitoring for disease recurrence but also in quantitative analysis of treatment outcomes and prediction of treatment response. The public health impact on the prevention of blindness from DR, AMD, and other retinal vascular diseases remains to be determined.},
}
@article {pmid39209113,
year = {2025},
author = {Campochiaro, PA and Eichenbaum, D and Chang, MA and Clark, WL and Graff, JM and Le Pogam, S and Cavichini Cordeiro, M and Gune, S and Rabena, M and Singh, N and Lin, S and Callaway, N},
title = {Interim Results of the Phase III Portal Extension Trial of the Port Delivery System with Ranibizumab in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {2},
pages = {144-155},
doi = {10.1016/j.oret.2024.05.021},
pmid = {39209113},
issn = {2468-6530},
mesh = {Humans ; *Ranibizumab/administration &amp; dosage ; Intravitreal Injections ; Male ; *Wet Macular Degeneration/drug therapy/diagnosis ; Angiogenesis Inhibitors/administration &amp; dosage ; Female ; *Visual Acuity ; Aged ; Treatment Outcome ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; *Drug Delivery Systems ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Dose-Response Relationship, Drug ; Middle Aged ; Fundus Oculi ; },
abstract = {OBJECTIVE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration (nAMD). Portal (NCT03683251) is evaluating long-term safety and tolerability of the PDS in patients with nAMD who completed the phase II Ladder (NCT02510794) or phase III Archway (NCT03677934) trials.<br><br>DESIGN: Multicenter, nonrandomized, open-label, extension clinical trial.<br><br>PARTICIPANTS: All-PDS safety population (N&#xa0;= 555) comprises patients enrolled in Portal who completed Ladder or Archway. Because of data availability, efficacy population comprises Ladder-to-Portal patients only: patients who previously received PDS 10, 40, or 100 mg/mL pro re nata (as-needed [PRN]; n&#xa0;= 58, 62, and 59, respectively) or monthly intravitreal ranibizumab 0.5-mg injections (monthly ranibizumab; n&#xa0;= 41) in Ladder and subsequently enrolled in Portal.<br><br>METHODS: Ladder patients received PDS refill-exchanges PRN or monthly ranibizumab. Archway patients received PDS 100 mg/mL with fixed refill-exchanges every 24 weeks (Q24W) or monthly ranibizumab. Once enrolled in Portal, all patients receive PDS Q24W from day&#xa0;1.<br><br>MAIN OUTCOME MEASURES: Ocular adverse events of special interest (AESIs); changes from baseline in best-corrected visual acuity (BCVA) and center point thickness (CPT); supplemental ranibizumab treatment between refill-exchange procedures; and PDS Patient Preference Questionnaire results.<br><br>RESULTS: In the All-PDS safety population (mean follow-up, 111 weeks), 137 (24.7%) patients had &#x2265;1 ocular AESI; most common were cataract (11.4%), vitreous hemorrhage (6.1%), and conjunctival thickening (bleb)/filtering bleb leak (6.3%). Endophthalmitis occurred in 11 of 555 (2.0%) patients. For Ladder-to-Portal patients previously treated with PDS 100 mg/mL or monthly ranibizumab, BCVA remained stable from baseline to month 48; mean (95% confidence interval) changes from baseline were 0.1 (-6.6 to 6.8; n&#xa0;= 31) and 2.3 (-9.4 to 14.1; n&#xa0;= 15) letters, respectively; CPT remained stable through month 48. Approximately 95% of patients did not need supplemental treatment before each refill-exchange for >2 years since Portal enrollment. Of Ladder-to-Portal previous monthly ranibizumab patients, 92% preferred the PDS over injections.<br><br>CONCLUSIONS: Interim results from Portal suggest 4-year maintenance of visual/anatomic outcomes with PDS 100 mg/mL, with the PDS preferred to monthly injections. Long-term safety profile of the PDS is well characterized.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39208778,
year = {2024},
author = {Viola, F and Chi, GC and Holekamp, NM and Giocanti-Aurégan, A and García-Layana, A and Peto, T and Kertes, PJ and Mirt, M and Kotecha, A and Lambert, J and Lewis, HB and Gentile, B},
title = {Caregiver Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {516-527},
doi = {10.1159/000540390},
pmid = {39208778},
issn = {1423-0259},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Diabetic Retinopathy/drug therapy ; Middle Aged ; *Macular Edema/drug therapy/etiology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Caregivers/psychology ; Aged ; *Wet Macular Degeneration/drug therapy ; *Intravitreal Injections ; Surveys and Questionnaires ; Visual Acuity ; Ranibizumab/administration &amp; dosage/therapeutic use ; Quality of Life ; Bevacizumab/therapeutic use/administration &amp; dosage ; },
abstract = {INTRODUCTION: Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) require frequent anti-vascular endothelial growth factor (VEGF) treatment and monitoring visits. We aimed to understand the burden of treatment on caregivers.<br><br>METHODS: This multinational, noninterventional study used a cross-sectional survey of adult patients with DME or nAMD treated with anti-VEGF injections in the USA, Canada, France, Italy, Spain, and the UK. The survey assessed caregivers' sociodemographic characteristics, patient relationships, patients' clinical history and treatment experiences, caregivers' experiences, and the Caregiver Reaction Assessment of caregiving burden.<br><br>RESULTS: Caregivers for patients with DME (n = 30) and nAMD (n = 95) completed surveys. Mean &#xb1; standard deviation (SD) age was 64.0 &#xb1; 13.4 years, and most were female (71.2%), white (70.4%), married (66.4%), and from Europe (67.2%). Most were caring for their mother/father or partner/spouse (85.6%). Mean &#xb1; SD length of time as a caregiver was 9.1 &#xb1; 10.0 years. Caregivers estimated they provided support for 4.2 &#xb1; 2.9 days/week and 6.0 &#xb1; 7.1 h/day on average. Nearly half of caregivers (45.6%) reported some impairment in daily activities, and more than two-thirds (70.5%) of working caregivers (n = 44) reported work absenteeism due to anti-VEGF treatment/monitoring appointments. At least one treatment barrier was reported by 66.7% and 50.5% of caregivers of patients with DME and nAMD, respectively, which were related to coronavirus disease 2019- (38.4%), clinic- (18.4%), social-/health- (13.6%), treatment- (10.4%), or financial-related factors (4.8%). Caregiver Reaction Assessment scores indicated mild-to-moderate burden, with higher caregiver schedule disruption scores associated with an increasing number of anti-VEGF treatment/monitoring visits among DME caregivers (r = 0.61).<br><br>CONCLUSION: Caregivers devote substantial time to caregiving, leading to schedule disruptions and absenteeism for some working caregivers. Positive and negative impacts on caregiver mental health were reported.},
}
@article {pmid39206403,
year = {2024},
author = {Chen, X and Qin, X and Bai, W and Ren, J and Yu, Y and Nie, H and Li, X and Liu, Z and Huang, J and Li, J and Yao, J and Jiang, Q},
title = {Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation.},
journal = {Advanced pharmaceutical bulletin},
volume = {14},
number = {2},
pages = {469-482},
pmid = {39206403},
issn = {2228-5881},
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV).<br><br>METHODS: Various experiments were conducted to assess the Kavain's toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed.<br><br>RESULTS: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE)/choroid complexes (P<0.05). Mechanistically, Kavain decreased the activity of the hypoxia-inducible factor 1&#x3b1; (HIF-1&#x3b1;)/VEGF-A/ VEGF receptor 2 (VEGFR2) signaling pathway.<br><br>CONCLUSION: Our study is the first to demonstrate Kavain's potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.},
}
@article {pmid39205438,
year = {2024},
author = {Neri, G and Olivieri, C and Serafino, S and Viggiano, P and Marolo, P and Reibaldi, M and Borrelli, E},
title = {Choriocapillaris in Age-Related Macular Degeneration.},
journal = {Turkish journal of ophthalmology},
volume = {54},
number = {4},
pages = {228-234},
pmid = {39205438},
issn = {2149-8709},
mesh = {Humans ; *Choroid/blood supply/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis ; Capillaries/pathology/diagnostic imaging ; Regional Blood Flow/physiology ; },
abstract = {Age-related macular degeneration (AMD) is a multifactorial disease characterized by progressive alterations of different retinal structures ultimately leading to vision loss. Among these, the choriocapillaris (CC) has been found to be affected in different stages of AMD. In this review we provide a discussion on the different stages of AMD, focusing particularly on the alterations involving the CC. This has been possible thanks to the introduction of optical coherence tomography-angiography, a recently developed imaging technique which allows the detection of blood flow in choroidal vessels. Therefore, the aim of this review is to provide a description of the various alterations involving the CC in the different stages of AMD.},
}
@article {pmid39204112,
year = {2024},
author = {Wu, KY and Gao, A and Giunta, M and Tran, SD},
title = {What's New in Ocular Drug Delivery: Advances in Suprachoroidal Injection since 2023.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {8},
pages = {},
pmid = {39204112},
issn = {1424-8247},
abstract = {Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024.},
}
@article {pmid39204105,
year = {2024},
author = {Estarreja, J and Mendes, P and Silva, C and Camacho, P and Mateus, V},
title = {Off-Label Use of Bevacizumab in Patients Diagnosed with Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {8},
pages = {},
pmid = {39204105},
issn = {1424-8247},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly people. Current pharmacological treatment in vascular AMD includes anti-VEGF agents, such as ranibizumab and aflibercept. Additionally, the off-label use of bevacizumab has been shown to be effective and has a lower cost, making it an interesting pharmacological approach; however, there is no consensus about its use. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy, safety, and efficiency of bevacizumab in AMD patients.<br><br>METHODS: This review only focused on randomized controlled clinical trials published in 2010 in the MEDLINE database that compared the effect of bevacizumab with ranibizumab. The risk of bias in each included study was assessed using the CASP Randomised Clinical Trials checklist.<br><br>RESULTS: Twelve studies were included for qualitative synthesis, and nine of them were considered for meta-analysis. Bevacizumab-treated patients showed a significantly reduced neovascularization in a longer spectrum of time; however, they had a higher incidence of endophthalmitis than those treated with ranibizumab. Regarding efficiency, the mean number of administrations was reduced in the treatment with bevacizumab in comparison to ranibizumab.<br><br>CONCLUSIONS: Clinical evidence demonstrates that bevacizumab has efficacy and safety profiles comparable with ranibizumab; however, it is relatively more efficient.},
}
@article {pmid39204083,
year = {2024},
author = {Frostegård, A and Haegerstrand, A},
title = {New Therapeutic Strategies in Retinal Vascular Diseases: A Lipid Target, Phosphatidylserine, and Annexin A5-A Future Theranostic Pairing in Ophthalmology.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {8},
pages = {},
pmid = {39204083},
issn = {1424-8247},
abstract = {Despite progress in the management of patients with retinal vascular and degenerative diseases, there is still an unmet clinical need for safe and effective therapeutic options with novel mechanisms of action. Recent mechanistic insights into the pathogenesis of retinal diseases with a prominent vascular component, such as retinal vein occlusion (RVO), diabetic retinopathy (DR) and wet age-related macular degeneration (AMD), may open up new treatment paradigms that reach beyond the inhibition of vascular endothelial growth factor (VEGF). Phosphatidylserine (PS) is a novel lipid target that is linked to the pathophysiology of several human diseases, including retinal diseases. PS acts upstream of VEGF and complement signaling pathways. Annexin A5 is a protein that targets PS and inhibits PS signaling. This review explores the current understanding of the potential roles of PS as a target and Annexin A5 as a therapeutic. The clinical development status of Annexin A5 as a therapeutic and the potential utility of PS-Annexin A5 as a theranostic pairing in retinal vascular conditions in particular is described.},
}
@article {pmid39203931,
year = {2024},
author = {Gemae, MR and Bassi, MD and Wang, P and Chin, EK and Almeida, DRP},
title = {NAD+ and Niacin Supplementation as Possible Treatments for Glaucoma and Age-Related Macular Degeneration: A Narrative Review.},
journal = {Nutrients},
volume = {16},
number = {16},
pages = {},
pmid = {39203931},
issn = {2072-6643},
mesh = {Humans ; *Niacin/administration &amp; dosage/therapeutic use/pharmacology ; *Dietary Supplements ; *Macular Degeneration/drug therapy/prevention &amp; control ; *NAD/metabolism ; *Glaucoma/drug therapy ; *Oxidative Stress/drug effects ; Animals ; },
abstract = {Glaucoma and age-related macular degeneration (AMD) are progressive retinal diseases characterized by increased oxidative stress, inflammation, and mitochondrial dysfunction. This review investigates the potential therapeutic benefits of NAD+ and niacin supplementation in managing glaucoma and AMD. A literature search was conducted encompassing keywords such as "niacin", "NAD", "glaucoma", "AMD", and "therapeutics". NAD+ depletion is associated with increased oxidative stress and mitochondrial dysfunction in glaucoma and AMD. Niacin, a precursor to NAD+, has shown promise in replenishing NAD+ levels, improving choroidal blood flow, and reducing oxidative damage. Animal studies in glaucoma models indicate that nicotinamide (NAM) supplementation preserves RGC density and function. Large-scale population-based studies indicate an inverse correlation between niacin intake and glaucoma prevalence, suggesting a preventative role. Randomized controlled trials assessing niacin supplementation showed significant improvements in visual field sensitivity and inner retinal function, with a dose-dependent relationship. In AMD, nicotinamide supplementation may improve rod cell function and protect against oxidative stress-induced damage. Cross-sectional studies reveal that individuals with AMD have a lower dietary intake of niacin. Further studies suggest niacin's role in improving choroidal blood flow and dilating retinal arterioles, potentially mitigating ischemic damage and oxidative stress in AMD. Beyond current management strategies, NAD+ and niacin supplementation may offer novel therapeutic avenues for glaucoma and AMD. Further research is warranted to elucidate their efficacy and safety in clinical settings.},
}
@article {pmid39201313,
year = {2024},
author = {Yang, TH and Kang, EY and Lin, PH and Yu, BB and Wang, JH and Chen, V and Wang, NK},
title = {Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.},
journal = {International journal of molecular sciences},
volume = {25},
number = {16},
pages = {},
pmid = {39201313},
issn = {1422-0067},
support = {grants//Gerstner Philanthropies/ ; Award Number R01EY031354 and 5P30EY019007//National Eye Institute of the National Institutes of Health/ ; R01 EY031354/EY/NEI NIH HHS/United States ; P30 EY019007/EY/NEI NIH HHS/United States ; grants//The Vagelos College of Physicians &amp; Surgeons (VP&amp;S)/ ; an Unrestricted Grant to the Department of Ophthalmology, Columbia University//Research to Prevent Blindness, New York, NY/ ; },
mesh = {Humans ; *Oxidative Stress ; *Retinal Ganglion Cells/metabolism/pathology ; *Mitochondria/metabolism ; Animals ; Reactive Oxygen Species/metabolism ; Glaucoma/metabolism/pathology ; },
abstract = {This review explored the role of mitochondria in retinal ganglion cells (RGCs), which are essential for visual processing. Mitochondrial dysfunction is a key factor in the pathogenesis of various vision-related disorders, including glaucoma, hereditary optic neuropathy, and age-related macular degeneration. This review highlighted the critical role of mitochondria in RGCs, which provide metabolic support, regulate cellular health, and respond to cellular stress while also producing reactive oxygen species (ROS) that can damage cellular components. Maintaining mitochondrial function is essential for meeting RGCs' high metabolic demands and ensuring redox homeostasis, which is crucial for their proper function and visual health. Oxidative stress, exacerbated by factors like elevated intraocular pressure and environmental factors, contributes to diseases such as glaucoma and age-related vision loss by triggering cellular damage pathways. Strategies targeting mitochondrial function or bolstering antioxidant defenses include mitochondrial-based therapies, gene therapies, and mitochondrial transplantation. These advances can offer potential strategies for addressing mitochondrial dysfunction in the retina, with implications that extend beyond ocular diseases.},
}
@article {pmid39201034,
year = {2024},
author = {Cennamo, G and Rinaldi, M and Chiosi, F and Costagliola, C},
title = {Changes in Macular Pigment Optical Density after Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration: A Pilot Study.},
journal = {Journal of clinical medicine},
volume = {13},
number = {16},
pages = {},
pmid = {39201034},
issn = {2077-0383},
abstract = {Background: This study aimed to evaluate the effects of faricimab intravitreal injections in patients with exudative age macular degeneration (nAMD) after the loading dose using spectral domain optical coherence tomography (SD-OCT) and macular pigment optical density (MPOD). Methods: In this observational prospective study, we enlisted a total of 12 consecutive eyes of 12 patients (six females, six males; mean age 70.47 ± 2.46 years) affected by nAMD who consecutively presented to the Eye Clinic of the University of Naples "Federico II" and Monaldi Hospital of Naples, from June 2023 to December 2023. All patients received four once-monthly intravitreal injections of faricimab (6 mg/0.05 mL) (loading phase). At baseline and 1 month after the fourth faricimab monthly injection, all patients underwent assessment of best correct visual acuity (BCVA) and ophthalmic examination, including slit-lamp biomicroscopy, intraocular pressure (IOP), fundus biomicroscopy, SD-OCT, and MPOD. Results: A total of 12 eyes of 12 patients (six women, six men; mean age 70.47 ± 2.46 years) were included in this study. A statistically significant raise in BCVA and MOPD parameters was shown between baseline and after the loading phase (p < 0.001). Conclusions: Intravitreal injections of faricimab led in the short term to a significant functional and MPOD improvement along with a decrease in central macular thickness (CMT) and thus appears to be an effective treatment option without relevant adverse effects. MOPD may be considered as a prognostic factor associated with a good visual prognosis after intravitreal injections treatment.},
}
@article {pmid39200753,
year = {2024},
author = {Thananjeyan, AL and Arnold, J and Lee, M and Au, C and Pye, V and Madigan, MC and Cherepanoff, S},
title = {Basal Linear Deposit: Normal Physiological Ageing or a Defining Lesion of Age-Related Macular Degeneration?.},
journal = {Journal of clinical medicine},
volume = {13},
number = {16},
pages = {},
pmid = {39200753},
issn = {2077-0383},
support = {//Sarks Foundation (SC); Drs Shirley and John Sarks via the Curran Foundation (VP, ML, CA)/ ; },
abstract = {Objective: To determine if basal linear deposit (BLinD) is a specific lesion of age-related macular degeneration (AMD). Methods: The cohort was selected from a clinically and histopathologically validated archive (Sarks Archive) and consisted of 10 normal eyes (age 55-80 years) without any macular basal laminar deposit (BLamD) (Sarks Group I) and 16 normal aged eyes (age 57-88 years) with patchy BLamD (Sarks Group II). Only eyes with in vivo fundus assessment and corresponding high-resolution transmission electron microscopy (TEM) micrographs of the macula were included. Semithin sections and fellow-eye paraffin sections were additionally examined. BLinD was defined as a diffuse layer of electron-lucent vesicles external to the retinal pigment epithelium (RPE) basement membrane by TEM and was graded as follows: (i) Grade 0, absence of a continuous layer; (ii) Grade 1, a continuous layer up to three times the thickness of the RPE basement membrane (0.9 µm); (iii) Grade 2, a continuous layer greater than 0.9 µm. Bruch's membrane (BrM) hyalinisation and RPE abnormalities were determined by light microscopic examination of corresponding semithin and paraffin sections. Results: BLinD was identified in both normal (30%) and normal aged (62.5%) eyes. BLinD was thicker in normal aged eyes (p = 0.045; 95% CI 0.04-3.4). BLinD thickness positively correlated with both the degree of BrM hyalinisation (p = 0.049; 95% CI 0.05-2.69) and increasing microscopic RPE abnormalities (p = 0.022; 95% CI 0.188-2.422). RPE abnormalities were more likely to be observed in eyes with increased BrM hyalinisation (p = 0.044; 95% CI 0.61-4.319). Conclusions: BLinD is most likely an age-related deposit rather than a specific lesion of AMD. Its accumulation is associated with increasing BrM hyalinisation and microscopic RPE abnormalities, suggesting a relationship with dysregulated RPE metabolism and/or transport.},
}
@article {pmid39200358,
year = {2024},
author = {Khalatyan, AS and Shishparenok, AN and Avetisov, KS and Gladilina, YA and Blinova, VG and Zhdanov, DD},
title = {Association of Telomere Length in T Lymphocytes, B Lymphocytes, NK Cells and Monocytes with Different Forms of Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {12},
number = {8},
pages = {},
pmid = {39200358},
issn = {2227-9059},
abstract = {BACKGROUND: Age plays a primary role in the development of age-related macular degeneration (AMD). Telomere length (TL) is one of the most relevant biomarkers of aging. In our study, we aimed to determine the association of TL with T lymphocytes, B lymphocytes, NK cells or monocytes with different forms of AMD.<br><br>METHODS: Our study included 62 patients with AMD: geographic atrophy (GA), neovascular AMD (NVAMD) with and without macular atrophy and 22 healthy controls. Each leukocyte subtype was isolated from peripheral blood by immunomagnetic separation, and the DNA was purified. The TL in the genomic DNA was determined using qPCR by amplifying the telomere region with specific oligonucleotide primers and normalizing to the control gene. Statistical analysis was performed using R version 4.5.1.<br><br>RESULTS: We observed a statistically significant increase in TL in the T cells between the control and NVAMD groups but not for the GA group. The B cells and monocytes showed a significant decrease in TL in all AMD groups. The TL in the NK cells did not decrease in any of the AMD groups.<br><br>CONCLUSIONS: The TL in the monocytes had the strongest association with AMD. It reflects a person's "telomeric status" and may become a diagnostic hallmark of these degenerative processes.},
}
@article {pmid39199806,
year = {2024},
author = {Shmueli, O and Szeskin, A and Benhamou, I and Joskowicz, L and Shwartz, Y and Levy, J},
title = {Measuring Geographic Atrophy Area Using Column-Based Machine Learning Software on Spectral-Domain Optical Coherence Tomography versus Fundus Auto Fluorescence.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {8},
pages = {},
pmid = {39199806},
issn = {2306-5354},
support = {Integra grant//Hebrew University of Jerusalem/ ; },
abstract = {BACKGROUND: The purpose of this study was to compare geographic atrophy (GA) area semi-automatic measurement using fundus autofluorescence (FAF) versus optical coherence tomography (OCT) annotation with the cRORA (complete retinal pigment epithelium and outer retinal atrophy) criteria.<br><br>METHODS: GA findings on FAF and OCT were semi-automatically annotated at a single time point in 36 pairs of FAF and OCT scans obtained from 36 eyes in 24 patients with dry age-related macular degeneration (AMD). The GA area, focality, perimeter, circularity, minimum and maximum Feret diameter, and minimum distance from the center were compared between FAF and OCT annotations.<br><br>RESULTS: The total GA area measured on OCT was 4.74 &#xb1; 3.80 mm[2]. In contrast, the total GA measured on FAF was 13.47 &#xb1; 8.64 mm[2] (p < 0.0001), with a mean difference of 8.72 &#xb1; 6.35 mm[2]. Multivariate regression analysis revealed a significant correlation between the difference in area between OCT and FAF and the total baseline lesion perimeter and maximal lesion diameter measured on OCT (adjusted r[2]: 0.52; p < 0.0001) and the total baseline lesion area measured on FAF (adjusted r[2]: 0.83; p < 0.0001).<br><br>CONCLUSIONS: We report that the GA area measured on FAF differs significantly from the GA area measured on OCT. Further research is warranted in order to determine the clinical relevance of these findings.},
}
@article {pmid39198703,
year = {2024},
author = {Armendariz, BG and Chakravarthy, U},
title = {Fibrosis in age-related neovascular macular degeneration in the anti-VEGF era.},
journal = {Eye (London, England)},
volume = {38},
number = {17},
pages = {3243-3251},
pmid = {39198703},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Fibrosis ; *Wet Macular Degeneration/drug therapy ; Macular Degeneration/drug therapy ; Biomarkers ; Choroidal Neovascularization/drug therapy ; },
abstract = {The natural history of neovascular age-related macular degeneration (nAMD) leads to scarring and loss of vision. Since the advent of anti-VEGF therapies, which are very effective for controlling exudation, large disciform scars are rarely encountered in the clinic. However long term studies show that smaller and less severe fibrotic scars are not uncommon and develop over time despite optimal treatment. This means that additional mechanisms of action may be required to completely address this condition. To permit new treatments, a proper understanding of the clinical impact of fibrosis is required. This review is focused on clinical aspects of fibrosis and summarises recent data on biomarkers, prevalence, causes, consequences, and therapies, highlighting the most important and urgent topics to tackle in order to advance in the treatment of fibrosis.},
}
@article {pmid39198593,
year = {2024},
author = {Sharma, P and Kalaw, FGP and Lin, A and Walker, EH and Borooah, S},
title = {Developing an image-based grading scale for peripheral drusen to investigate associations of peripheral drusen type with age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {20041},
pmid = {39198593},
issn = {2045-2322},
support = {P30 EY022589/EY/NEI NIH HHS/United States ; CD-GT-0918-0746-SE//Foundation Fighting Blindness grant/ ; OT2 OD032644/OD/NIH HHS/United States ; P30EY022589//UCSD Vision research core grant/ ; OT2OD032644//National Institutes of Health Bridge2AI (AI-READI) Project Grant/ ; },
mesh = {Humans ; Female ; Male ; *Retinal Drusen/diagnostic imaging/pathology ; *Macular Degeneration/diagnostic imaging/pathology/complications ; Aged ; *Tomography, Optical Coherence/methods ; Aged, 80 and over ; Retina/diagnostic imaging/pathology ; Severity of Illness Index ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness. It is associated with peripheral drusen which has not been categorized. We investigated peripheral drusen to validate an image grading system and to understand possible associations between peripheral drusen and AMD. We collated clinical data, ultra-widefield (UWF) pseudocolor fundus images and Spectral-Domain Optical Coherence Tomography (SD-OCT) scans from consecutive retinal patients. SD-OCT scans were used to determine AMD stage. A masked retinal specialist recorded the types of peripheral drusen observed in UWF images. Eyes whose UWF images did not pass quality screening and those without AMD and peripheral drusen were excluded from the study. Statistical tests were utilized to determine the validity of our grading system and associations of peripheral drusen with AMD. A total of 481 eyes (283 subjects) were included in the study (mean age 73.1 ± 1.2years, 64.3% female). Interobserver and test-retest statistical analyses to evaluate the UWF image grading system resulted in Cohen's Kappa 0.649 (p < 0.001) and 0.922 (p < 0.001) respectively. A total of 284 (59.0%), 28 (5.8%), 15 (3.1%), 22 (4.6%), 4 (0.8%), 39 (8.1%), and 32 (6.7%) eyes had hard, soft, reticular, cuticular, atrophic, mixed drusen, and mixed drusen and atrophy respectively in at least one peripheral retinal quadrant. Hard peripheral drusen was significantly associated with the presence of AMD (p = 0.010). Peripheral drusen types were variably seen in retinal patients with and without AMD. We validated a peripheral drusen grading system and provided an image library to assist in the identification of peripheral drusen. Our study found an association between peripheral hard drusen and an AMD diagnosis but did not find a link between peripheral drusen and severity of AMD.},
}
@article {pmid39197675,
year = {2024},
author = {Chen, Q and Zhang, J and Liu, X and Xu, K and Guo, H and Li, Y and Liang, J and Li, Y and Liang, L},
title = {Exploring the protective effects of Qiju Granule in a rat model of dry age-related macular degeneration.},
journal = {Experimental gerontology},
volume = {196},
number = {},
pages = {112556},
doi = {10.1016/j.exger.2024.112556},
pmid = {39197675},
issn = {1873-6815},
mesh = {Animals ; *Disease Models, Animal ; *Macular Degeneration/prevention &amp; control/metabolism/pathology/drug therapy ; Male ; *Drugs, Chinese Herbal/pharmacology ; *Electroretinography ; Rats ; *Retina/drug effects/metabolism/pathology ; *Tomography, Optical Coherence ; *Rats, Sprague-Dawley ; Fibroblast Growth Factor 2/metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Iodates ; Glial Fibrillary Acidic Protein/metabolism/genetics ; Ciliary Neurotrophic Factor ; },
abstract = {AIM: The aim of this study was to evaluate the potential protective effect of Qiju Granule in a rat model of age-related macular degeneration (AMD) and investigate the underlying mechanisms involved.<br><br>METHODS: Rats were injected intravenously with 40&#xa0;mg/kg of sodium iodate (SI) to induce a dry AMD model. The rats in the treatment group received three different doses of Qiju Granule once a day via gavage, while the rats in the control group were given an equal volume of physiological saline. On day 14 and day 28 following the intervention, various methods were employed to evaluate retinal function and structure, including electroretinography (ERG), optical coherence tomography (OCT), and histological examination. The expression of glial fibrillary acidic protein (GFAP), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) was assessed via immunofluorescence. Beyond immunofluorescence, the mRNA levels of bFGF, BDNF, and CNTF were quantitatively determined using real-time polymerase chain reaction (qRT-PCR).<br><br>RESULTS: Rats treated with Qiju Granule exhibited significant improvements in both retinal function and structure compared to the model group. The most noteworthy effects were observed at a high dose of Qiju Granule. Furthermore, the expression levels of bFGF, BDNF, and CNTF were significantly unregulated in the treated groups compared to the model group.<br><br>CONCLUSIONS: Qiju Granule demonstrated a protective effect on the retina in the SI-induced rat model of AMD. The protective mechanism may be attributed to the upregulation of retinal neurotrophic factors expression.},
}
@article {pmid39197428,
year = {2024},
author = {Chi, SC and Weng, CC and Chen, SJ and Lin, TC and Chou, YB and Hwang, DK},
title = {The Short-Term Efficacy and Safety of Faricimab in Refractory Neovascular Age-Related Macular Degeneration: The Real-World Experience in Taiwan.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {5-6},
pages = {312-321},
doi = {10.1159/000540833},
pmid = {39197428},
issn = {1423-0267},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Taiwan/epidemiology ; *Intravitreal Injections ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Treatment Outcome ; *Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Time Factors ; Fluorescein Angiography/methods ; Aged, 80 and over ; Fundus Oculi ; Middle Aged ; },
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) treatment stands as the primary approach for neovascular age-related macular degeneration (nAMD). Faricimab has recently emerged as a novel anti-VEGF option for nAMD. This study aimed to assess the efficacy of faricimab in patients with refractory nAMD.<br><br>METHOD: This retrospective study focused on refractory nAMD patients treated with faricimab at Taipei Veterans General Hospital from March 2023 to December 2023. Primary outcomes assessed the change in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over the first 4 months. Secondary outcomes included the presence of subretinal and intraretinal fluid (SRF and IRF) and changes in pigment epithelial detachment (PED). Subgroup analysis for the successful and unsuccessful treatment groups was conducted to identify potential confounding factors influencing treatment response.<br><br>RESULT: This study included 42 eyes with refractory nAMD treated with faricimab. During a 6-month follow-up, no significant improvement in BCVA was observed, while CRT significantly decreased at all time points, except during the 5-month follow-up. Height PED showed significant reduction up to 5 months. The prevalence of SRF decreased significantly, while IRF remained lower but not significant. According to the treatment criteria, 67.4% successfully met the treatment goals. Subgroup analysis between successful and unsuccessful groups showed no significant differences in baseline characteristics, except a higher predominantly serous PED percentage in the successful group.<br><br>CONCLUSION: Faricimab showed favorable outcomes in refractory nAMD patients. Further investigations are needed to understand the factors contributing to its efficacy.},
}
@article {pmid39193319,
year = {2024},
author = {Bakri, SJ and Amoaku, WMK and Altman, D and Quéré, S and Quilantan, J and Carpenter-Conlin, J and Sarda, SP and Jones, DL and Nielsen, JS},
title = {The MOSAIC Study: A Mixed-Methods Study of the Clinical, Emotional, and Financial Burden of Geographic Atrophy Among Patients and Caregivers in the US.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {2357-2368},
pmid = {39193319},
issn = {1177-5467},
abstract = {PURPOSE: Geographic atrophy (GA) impacts both patients and caregivers, yet little is understood about their respective burdens. The MOSAIC study aimed to identify the clinical, emotional, and financial burden among patients with GA and caregivers.<br><br>METHODS: A total of 28 patients with GA and 17 caregivers from the United States (US), the United Kingdom, and Australia participated in individualized qualitative interviews followed by a cross-sectional quantitative survey of 102 patients and 102 caregivers in the US. Interview transcripts were analyzed to develop conceptual models, which were then used to guide the design of quantitative surveys. Data were described at the item level and score level when appropriate (National Eye Institute Visual Function Questionnaire [NEI VFQ]-39 and Zarit Burden Interview [ZBI]). For the patient/caregiver dyad sample, the association between the NEI VFQ-39 scores and ZBI score was explored through correlation coefficients and scatterplots.<br><br>RESULTS: GA had a substantial impact on patients' vision-related quality of life, activities of daily living, and instrumental activities of daily living. There was considerable overlap between perspectives and key concerns identified by patients and caregivers. Eighty-three percent of caregivers reported having to drive patients to appointments due to limited patient mobility, for example, and 41% reported a change in their employment status after becoming a caregiver, with 50% of them unable to work due to caregiving. The burden of patients and caregivers had a correlation ranging from -0.63 to -0.21 between NEI VFQ-39 subscale and composite scores and ZBI score.<br><br>CONCLUSION: This study confirms the paucity of support for both patients with GA and caregivers. Both groups require expanded access to financial, social, and mental health resources.},
}
@article {pmid39193222,
year = {2024},
author = {Belete, GT and Zhou, L and Li, KK and So, PK and Do, CW and Lam, TC},
title = {Metabolomics studies in common multifactorial eye disorders: a review of biomarker discovery for age-related macular degeneration, glaucoma, diabetic retinopathy and myopia.},
journal = {Frontiers in molecular biosciences},
volume = {11},
number = {},
pages = {1403844},
pmid = {39193222},
issn = {2296-889X},
abstract = {INTRODUCTION: Multifactorial Eye disorders are a significant public health concern and have a huge impact on quality of life. The pathophysiological mechanisms underlying these eye disorders were not completely understood since functional and low-throughput biological tests were used. By identifying biomarkers linked to eye disorders, metabolomics enables early identification, tracking of the course of the disease, and personalized treatment.<br><br>METHODS: The electronic databases of PubMed, Scopus, PsycINFO, and Web of Science were searched for research related to Age-Related macular degeneration (AMD), glaucoma, myopia, and diabetic retinopathy (DR). The search was conducted in August 2023. The number of cases and controls, the study's design, the analytical methods used, and the results of the metabolomics analysis were all extracted. Using the QUADOMICS tool, the quality of the studies included was evaluated, and metabolic pathways were examined for distinct metabolic profiles. We used MetaboAnalyst 5.0 to undertake pathway analysis of differential metabolites.<br><br>RESULTS: Metabolomics studies included in this review consisted of 36 human studies (5 Age-related macular degeneration, 10 Glaucoma, 13 Diabetic retinopathy, and 8 Myopia). The most networked metabolites in AMD include glycine and adenosine monophosphate, while methionine, lysine, alanine, glyoxylic acid, and cysteine were identified in glaucoma. Furthermore, in myopia, glycerol, glutamic acid, pyruvic acid, glycine, cysteine, and oxoglutaric acid constituted significant metabolites, while glycerol, glutamic acid, lysine, citric acid, alanine, and serotonin are highly networked metabolites in cases of diabetic retinopathy. The common top metabolic pathways significantly enriched and associated with AMD, glaucoma, DR, and myopia were arginine and proline metabolism, methionine metabolism, glycine and serine metabolism, urea cycle metabolism, and purine metabolism.<br><br>CONCLUSION: This review recapitulates potential metabolic biomarkers, networks and pathways in AMD, glaucoma, DR, and myopia, providing new clues to elucidate disease mechanisms and therapeutic targets. The emergence of advanced metabolomics techniques has significantly enhanced the capability of metabolic profiling and provides novel perspectives on the metabolism and underlying pathogenesis of these multifactorial eye conditions. The advancement of metabolomics is anticipated to foster a deeper comprehension of disease etiology, facilitate the identification of novel therapeutic targets, and usher in an era of personalized medicine in eye research.},
}
@article {pmid39187657,
year = {2024},
author = {Wijesingha, N and Kotecha, A and Margaron, P and Sivaprasad, S},
title = {Correction: Infographic: 2-year efficacy, durability and safety of intravitreal faricimab with treat-and-extend dosing up to 16 weeks in neovascular age-related macular degeneration (pooled results from TENAYA and LUCERNE).},
journal = {Eye (London, England)},
volume = {38},
number = {18},
pages = {3610},
doi = {10.1038/s41433-024-03309-5},
pmid = {39187657},
issn = {1476-5454},
}
@article {pmid39182665,
year = {2024},
author = {Hayashi, K and Kobayashi, M and Mori, K and Nakagawa, Y and Watanabe, B and Ashimori, A and Higashijima, F and Yoshimoto, T and Sunada, J and Morita, T and Murai, T and Kirihara-Kojima, S and Kimura, K},
title = {The benzoylphenylurea derivative BPU17 acts as an inhibitor of prohibitin and exhibits antifibrotic activity.},
journal = {Experimental cell research},
volume = {442},
number = {1},
pages = {114221},
doi = {10.1016/j.yexcr.2024.114221},
pmid = {39182665},
issn = {1090-2422},
mesh = {*Prohibitins ; Animals ; *Repressor Proteins/metabolism ; Humans ; Mice ; *Myofibroblasts/drug effects/metabolism/pathology ; *Fibrosis/drug therapy ; Antifibrotic Agents/pharmacology ; Epithelial-Mesenchymal Transition/drug effects ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Cell Movement/drug effects ; Mice, Inbred C57BL ; Macular Degeneration/drug therapy/metabolism/pathology ; Cells, Cultured ; Serum Response Factor/metabolism/antagonists &amp; inhibitors ; },
abstract = {Inflammation-induced choroidal neovascularization followed by the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) is a cause of neovascular age-related macular degeneration (nAMD). RPE-derived myofibroblasts overproduce extracellular matrix, leading to subretinal fibrosis. We already have demonstrated that benzylphenylurea (BPU) derivatives inhibit the function of cancer-associated fibroblasts. Here, we investigated the anti-myofibroblast effects of BPU derivatives and examined such BPU activity on subretinal fibrosis. A BPU derivative, BPU17, exhibits the most potent anti-myofibroblast activity among dozens of BPU derivatives and inhibits subretinal fibrosis in a mouse model of retinal degeneration. Investigations with primary cultured RPEs reveal that BPU17 suppresses cell motility and collagen synthesis in RPE-derived myofibroblasts. These effects depend on repressing the serum response factor (SRF)/CArG-box-dependent transcription. BPU17 inhibits the expression of SRF cofactor, cysteine and glycine-rich protein 2 (CRP2), which activates the SRF function. Proteomics analysis reveals that BPU17 binds to prohibitin 1 (PHB1) and inhibits the PHB1-PHB2 interaction, resulting in mild defects in mitochondrial function. This impairment causes a decrease in the expression of CRP2 and suppresses collagen synthesis. Our findings suggest that BPU17 is a promising agent against nAMD and the close relationship between PHB function and EMT.},
}
@article {pmid39182627,
year = {2025},
author = {Brown, DM and Jaffe, GJ and Wykoff, CC and Adiguzel, E and Heier, JS and Khanani, AM},
title = {MERLIN: Two-Year Results of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid.},
journal = {Ophthalmology},
volume = {132},
number = {2},
pages = {131-140},
doi = {10.1016/j.ophtha.2024.08.022},
pmid = {39182627},
issn = {1549-4713},
mesh = {Humans ; Female ; Double-Blind Method ; Intravitreal Injections ; Male ; Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Subretinal Fluid ; Tomography, Optical Coherence ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography ; Middle Aged ; },
abstract = {PURPOSE: To report the safety and efficacy of brolucizumab (Beovu) 6 mg versus aflibercept (Eylea) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the week 52 up to week 104.<br><br>DESIGN: Multicenter, randomized, double-masked phase 3a study.<br><br>PARTICIPANTS: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-VEGF treatment).<br><br>METHODS: Study eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks or until study termination.<br><br>MAIN OUTCOME MEASURES: All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]) and safety data up to study termination, including data up to week 104 for those participants who completed the study before its termination. All P values after week 52 were nominal and reflect observed data for the efficacy analyses.<br><br>RESULTS: Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to week 104 (least squares mean difference, -0.4 ETDRS letters; 95% confidence interval [CI], -3.7 to 3.0; P&#xa0;= 0.0169). The proportion of eyes with &#x2265;15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept (P = 0.7762), and a greater proportion of eyes were fluid free at week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab versus aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab versus 6.1% (0% and 0.6%) for aflibercept.<br><br>CONCLUSIONS: Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change, with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab versus aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39182598,
year = {2024},
author = {Tang, AC and Besley, NA and Trimpey-Warfhatig, R and Yang, P and Wessel, H and Brown, L and Kirshner, Z and Jaffe, GJ},
title = {The novel secretome ST266 activates Akt and protects against oxidative stress-mediated injury in human RPE and Müller cells.},
journal = {Experimental eye research},
volume = {248},
number = {},
pages = {110060},
doi = {10.1016/j.exer.2024.110060},
pmid = {39182598},
issn = {1096-0007},
mesh = {Humans ; *Oxidative Stress/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Cells, Cultured ; *Ependymoglial Cells/drug effects/metabolism ; Blotting, Western ; Cell Survival/drug effects ; Hydrogen Peroxide/toxicity ; Phosphorylation ; Membrane Potential, Mitochondrial/drug effects ; Oxidants/toxicity ; Signal Transduction/drug effects ; },
abstract = {Oxidative stress-mediated retinal pigment epithelial (RPE) cell damage is associated with age-related macular degeneration (AMD). ST266 is the biological secretome produced by a novel population of amnion-derived multipotent progenitor cells. Herein, we investigated the effect of ST266 on RPE cell injury induced by hydroquinone (HQ), a cigarette smoke related oxidant, hydrogen peroxide (H2O2) and all-trans retinal (atRal), a pro-oxidant component of the retinoid cycle. We additionally investigated its effect on Müller cell injury induced by H2O2. Cultured human RPE cells were pre-treated for 1 h in the presence or absence of MK-2206, a protein kinase B (Akt) inhibitor, then treated with varying concentrations of HQ, H2O2, or atRal for 1.5 h. Cultured human Müller cells (MIO-M1) were pre-treated for 1 h in the presence or absence of MK-2206, then treated with varying concentrations of H2O2 for 1.5 h. Media were then replaced with STM100 (control media into which the ST266 secretome proteins were collected) or ST266 at various times. Cell viability was determined with WST-1 reagent. Mitochondrial membrane potential (Δψm) was quantified by a fluorescence plate reader. The protein phosphorylation levels of Akt, glycogen synthase kinase 3 beta (GSK-3β), and p70 ribosomal S6 kinase (p70S6K) were measured by Western blot. ST266 significantly improved RPE and MIO-M1 cell viability that was reduced by oxidant exposure and improved oxidant-disrupted Δψm. In both cell types, ST266 induced phosphorylation of Akt, GSK-3β, and p70S6K. MK-2206 significantly eliminated ST266-mediated protein phosphorylation of Akt, GSK-3β, and p70S6K and abolished the ST266-protective effect on cell viability. In conclusion, ST266 activates Akt, protects against oxidative stress-mediated cell injury in an Akt-dependent manner, and improves Δψm, suggesting a potential role for ST266 therapy in treating retinal diseases such as AMD.},
}
@article {pmid39181749,
year = {2025},
author = {Chen, L},
title = {Non-steroidal anti-inflammatory drug use and age-related macular degeneration.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {124},
number = {5},
pages = {490-491},
doi = {10.1016/j.jfma.2024.08.026},
pmid = {39181749},
issn = {0929-6646},
}
@article {pmid39181460,
year = {2024},
author = {Kang, H and Park, SK and Kim, DH and Choi, YH},
title = {Exposure to per- and polyfluoroalkyl substances and age-related macular degeneration in U.S. middle-aged and older adults.},
journal = {Chemosphere},
volume = {364},
number = {},
pages = {143167},
doi = {10.1016/j.chemosphere.2024.143167},
pmid = {39181460},
issn = {1879-1298},
support = {R01 AG070897/AG/NIA NIH HHS/United States ; R01 ES026578/ES/NIEHS NIH HHS/United States ; R01 ES035087/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Fluorocarbons/blood ; *Macular Degeneration/epidemiology/chemically induced ; Middle Aged ; Female ; Aged ; Male ; *Alkanesulfonic Acids/blood ; *Environmental Exposure/statistics &amp; numerical data ; *Environmental Pollutants/blood ; United States/epidemiology ; *Caprylates/blood ; *Nutrition Surveys ; Sulfonic Acids/blood ; Adult ; Aged, 80 and over ; Fatty Acids ; },
abstract = {Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005-2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend = 0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.},
}
@article {pmid39181206,
year = {2024},
author = {Seddon, JM and De, D and Rosner, B},
title = {The role of nutritional factors in transitioning between early, mid, and late stages of age-related macular degeneration: prospective longitudinal analysis.},
journal = {The American journal of clinical nutrition},
volume = {120},
number = {6},
pages = {1387-1398},
pmid = {39181206},
issn = {1938-3207},
support = {R01 EY028602/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Diet ; Disease Progression ; Fatty Acids, Omega-3/administration &amp; dosage ; Longitudinal Studies ; Lutein/administration &amp; dosage ; *Macular Degeneration/prevention &amp; control ; Nutritional Status ; Prospective Studies ; Vegetables ; },
abstract = {BACKGROUND: Transitions between different stages of age-related macular degeneration (AMD) are not completely captured by traditional survival models with an end point of advanced AMD.<br><br>OBJECTIVES: This study aimed to explore the transitions from early and intermediate AMD to higher non-advanced and advanced stages and determine the contributions of nutritional factors to these outcomes.<br><br>METHODS: Eyes with early or intermediate AMD at baseline, classified according to the Age-Related Eye Disease Study severity scale, were included in this prospective longitudinal analysis. Foods and the biologically active nutrients associated with AMD [green leafy vegetables, fish, lutein/zeaxanthin (LZ), and &#x3c9;-3 (n-3) fatty acids] were determined by a baseline food frequency questionnaire. Progression was defined as eyes transitioning to higher severity groups including non-advanced and advanced stages over 5 years, confirmed at 2 consecutive visits. Cox proportional hazards models for foods and nutrients were analyzed adjusting for demographics, lifestyle, baseline macular status, a family history of AMD, caloric intake, and genetic risk.<br><br>RESULTS: Among 2697 eyes, 616 (23%) progressed to higher severity groups. In the food group model, higher intake of green leafy vegetables reduced incidence of transitions {hazard ratio [HR] (&#x2265;2.7 servings/wk compared with none): 0.75; 95% confidence interval [CI]: 0.59, 0.96; P = 0.02}
. Higher fish intake was also protective [HR (&#x2265; two 4-ounce servings/wk compared with <2): 0.79; 95% CI: 0.65, 0.95; P = 0.01]. In the nutrient model, LZ intake was protective [HR (&#x2265;2 mg/d compared with <2): 0.76; 95% CI: 0.60, 0.96; P = 0.02]. Higher intake of &#x3c9;-3 fatty acids also tended to be beneficial [HR (&#x2265;0.7 g/wk compared with <0.7): 0.85; 95% CI: 0.71, 1.01; P = 0.06].<br><br>CONCLUSIONS: Increased consumption of green leafy vegetables, LZ, and fish nutritionally rich in &#x3c9;-3 fatty acids during the initial stages of AMD may reduce rates of progression to higher severity of this debilitating disease. This trial was registered at clinicaltrials.gov as NCT00594672.},
}
@article {pmid39180057,
year = {2024},
author = {Kulikov, AN and Vasiliev, AS and Kalinicheva, YA and Maltsev, DS},
title = {Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {369},
pmid = {39180057},
issn = {1471-2415},
mesh = {Humans ; Administration, Topical ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Anti-Inflammatory Agents, Non-Steroidal/administration &amp; dosage ; *Benzophenones/administration &amp; dosage ; *Bromobenzenes/administration &amp; dosage ; Intravitreal Injections ; Macular Edema/drug therapy ; Ophthalmic Solutions/administration &amp; dosage ; Retinal Diseases/drug therapy/physiopathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; },
abstract = {BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies.<br><br>METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac.<br><br>RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p&#x2009;=&#x2009;0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p&#x2009;=&#x2009;0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported.<br><br>CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.},
}
@article {pmid39180041,
year = {2024},
author = {González-Montero, G and Guijarro Mata-García, M and Moreno Martínez, C and Recas Piorno, J},
title = {Rehab-AMD: co-design of an application for visual rehabilitation and monitoring of Age-related Macular Degeneration.},
journal = {BMC medical informatics and decision making},
volume = {24},
number = {1},
pages = {233},
pmid = {39180041},
issn = {1472-6947},
mesh = {Humans ; *Macular Degeneration/rehabilitation ; Software Design ; Telerehabilitation ; COVID-19 ; },
abstract = {BACKGROUND: The increasing demand for remote medical care, driven by digital healthcare advancements and the COVID-19 pandemic, necessitates effective solutions tailored to patients and healthcare practitioners. Co-design, involving collaboration between software developers, patients, and healthcare practitioners, prioritizes end-user needs. Research indicates that integrating patient perspectives enhances user experience and usability. However, its application in healthcare has been limited to small projects. This work focuses on co-designing a technological solution to enhance the monitoring and visual rehabilitation of individuals with Age-Related Macular Degeneration (AMD), a condition that significantly impacts the quality of life in people over 60. Current vision rehabilitation systems lack personalization, motivation, and effective progress monitoring. Involving patients and healthcare practitioners in the design process aims to ensure the final product meets their needs.<br><br>METHODS: The project employs iterative and collaborative principles, involving a vision rehabilitation expert and two AMD patients as active users in the application's development and validation. The process begins by establishing requirements for user accounts and rehabilitation exercises. It continues with an initial approach extended through user validation. Co-design is facilitated by specific workshops marking each project iteration, totaling four workshops, along with continuous communication sessions between experts and developers to validate design decisions. Initial requirements gathering and constant feedback from end-users, the visual rehabilitator, and patients are crucial for refining the product effectively.<br><br>RESULTS: The workshops produced a prototype featuring a test to monitor changes and progression and 15 visual rehabilitation exercises. Numerous patient and vision rehabilitation-driven software modifications led to a final design that is responsive and adaptive to end-user needs.<br><br>CONCLUSIONS: The Rehab-AMD pilot project aims to develop a collaborative and adaptive software solution for AMD rehabilitation by actively involving stakeholders and applying iterative design principles. Co-design in the Rehab-AMD solution proves to be a methodology that identifies usability issues and needs from the initial design stages. This approach ensures that software developers create a final product that is genuinely useful and manageable for people with AMD and the targeted vision rehabilitators.},
}
@article {pmid39179996,
year = {2024},
author = {Jemeberie, HA and Zeleke, TC and Tegegn, MT},
title = {Poor visual outcome and associated factors among patients underwent cataract surgery at Debre Markos and Felege Hiwot comprehensive specialized hospitals, Northwest Ethiopia, 2023.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {366},
pmid = {39179996},
issn = {1471-2415},
mesh = {Humans ; Ethiopia/epidemiology ; Cross-Sectional Studies ; Male ; Female ; Aged ; *Visual Acuity/physiology ; Middle Aged ; *Cataract Extraction ; Hospitals, Special/statistics &amp; numerical data ; Adult ; Cataract/complications/epidemiology ; Risk Factors ; Aged, 80 and over ; Lens Implantation, Intraocular ; Surveys and Questionnaires ; },
abstract = {OBJECTIVE: This study aimed to determine the proportion of poor visual outcome and associated factors among adult patients who underwent cataract surgery at Debre Markos and Felege Hiwot Comprehensive Specialized Hospitals in northwestern Ethiopia in 2023.<br><br>METHODS: A hospital based cross-sectional study was conducted on 418 adult patients who had undergone cataract surgery from June 07 to August 07, 2023. Patients were recruited using systematic random sampling with an interval of 2. A pre-tested semi-structured questionnaire, medical record review, and ophthalmologic examination were used to collect data. The collected data was entered into Epi-info version 7 and exported to SPSS version 25 software for analysis. Binary logistic regression was used to determine the factors associated with poor visual outcomes of cataract surgery. Variables with a p-value of less than 0.05 in the multivariable binary logistic regression were considered statistically significant.<br><br>RESULTS: A total of 408 study participants with a median age of 65 years and a response rate of 97.6% took part. The proportion of poor visual outcomes of cataract surgery from 4 weeks to one year was 25.7% (95%CI: 21.6%, 30.3%). Factors responsible for poor visual outcomes of cataract surgery were intraocular lens implantation without a posterior chamber (AOR&#x2009;=&#x2009;2.91, 95%CI:1.46,5.80), per-existing central corneal opacity (AOR&#x2009;=&#x2009;3.83, 95%CI:1.52,9.69), pseudoexfoliation (AOR&#x2009;=&#x2009;3.91,95%CI:1.39,11.88), age-related macular degeneration(AOR&#x2009;=&#x2009;3.75, 95%CI:1.22, 11.88), glaucoma (AOR&#x2009;=&#x2009;3.11, 95%CI:1.06,9.17) and striate keratopathy(AOR&#x2009;=&#x2009;3.4, 95%CI: 1.11, 10.88).<br><br>CONCLUSION: In this study, the proportion of poor visual outcomes of cataract surgery is higher than the World Health Organization recommendation. The study found that implantation of an intraocular lens without a posterior chamber, pre-existing central corneal opacity, pre-existing age-related macular degeneration, pre-existing glaucoma, pseudoexfoliation, and striate keratopathy were significantly associated with poor visual outcomes of cataract surgery. We recommend that ophthalmologists and cataract surgeons prioritize the reduction of surgical complications and pre-existing ocular co-morbidities to enhance post-operative visual acuity. Improving pre-operative assessment and refining surgical techniques like phacoemulsification will aid in achieving this goal.},
}
@article {pmid39179168,
year = {2024},
author = {Wang, Q and Zhu, M and Li, W and Guo, Y and Lou, H and Zhang, J and Xu, Y and Zeng, B and Wen, X and Ji, X and Xie, L},
title = {CBX7 promotes choroidal neovascularization by activating the HIF-1α/VEGF pathway in choroidal vascular endothelial cells.},
journal = {Experimental eye research},
volume = {247},
number = {},
pages = {110057},
doi = {10.1016/j.exer.2024.110057},
pmid = {39179168},
issn = {1096-0007},
mesh = {*Choroidal Neovascularization/metabolism/pathology/genetics ; Animals ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Mice ; *Polycomb Repressive Complex 1/metabolism/genetics ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; Humans ; *Choroid/blood supply/metabolism ; *Mice, Inbred C57BL ; *Disease Models, Animal ; Signal Transduction/physiology ; Cells, Cultured ; Blotting, Western ; Cell Proliferation/physiology ; Endothelial Cells/metabolism ; Gene Expression Regulation ; Endothelium, Vascular/metabolism/pathology ; Cell Movement ; Real-Time Polymerase Chain Reaction ; },
abstract = {Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α's transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV.},
}
@article {pmid39177654,
year = {2024},
author = {Kwon, YS and Han, Z},
title = {Advanced nanomedicines for the treatment of age-related macular degeneration.},
journal = {Nanoscale},
volume = {16},
number = {36},
pages = {16769-16790},
doi = {10.1039/d4nr01917b},
pmid = {39177654},
issn = {2040-3372},
mesh = {*Macular Degeneration/drug therapy ; Humans ; *Nanomedicine ; Nanoparticles/chemistry/therapeutic use ; Drug Delivery Systems ; Animals ; },
abstract = {The critical and unmet medical need for novel therapeutic advancements in the treatment of age-related macular degeneration (AMD) cannot be overstated, particularly given the aging global population and the increasing prevalence of this condition. Current AMD therapy involves intravitreal treatments that require monthly or bimonthly injections to maintain optimal efficacy. This underscores the necessity for improved approaches, prompting recent research into developing advanced drug delivery systems to prolong the intervals between treatments. Nanoparticle-based therapeutic approaches have enabled the controlled release of drugs, targeted delivery of therapeutic materials, and development of smart solutions for the harsh microenvironment of diseased tissues, offering a new perspective on ocular disease treatment. This review emphasizes the latest pre-clinical treatment options in ocular drug delivery to the retina and explores the advantages of nanoparticle-based therapeutic approaches, with a focus on AMD, the leading cause of irreversible blindness in the elderly.},
}
@article {pmid39177106,
year = {2025},
author = {Tarhan, M and Meller, D and Hammer, M},
title = {Hyperautofluorescent material inside areas of macular atrophy may reveal non-lipofuscin fluorophores in late stage AMD.},
journal = {Acta ophthalmologica},
volume = {103},
number = {1},
pages = {e66-e75},
pmid = {39177106},
issn = {1755-3768},
support = {HA4430/5-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; Female ; Male ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Fundus Oculi ; Aged ; *Lipofuscin/metabolism ; Optical Imaging/methods ; Macular Degeneration/diagnosis ; Geographic Atrophy/diagnosis ; Macula Lutea/pathology/diagnostic imaging ; Retrospective Studies ; },
abstract = {PURPOSE: To characterize fundus autofluorescence (FAF) in complete (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) by fluorescence lifetime imaging ophthalmology (FLIO).<br><br>METHODS: Overall, 98 macular atrophy (MA) lesions in 42 eyes of 37 age-related macular degeneration (AMD) patients (mean age: 80.9&#x2009;&#xb1;&#x2009;5.8&#x2009;years), 25 of them classified as iRORA and 73 as cRORA by OCT, were investigated by FLIO in a short (SSC: 498-560&#x2009;nm) and a long wavelength channel (LSC: 560-720&#x2009;nm). Differences of FAF lifetimes and peak emission wavelength (PEW) between atrophic lesions and intact retinal pigment epithelium (RPE) in the outer ring of the ETDRS grid were considered.<br><br>RESULTS: FAF lifetimes in MA were longer and PEW were significantly (p&#x2009;<&#x2009;0.001) shorter than in intact RPE by 112&#x2009;&#xb1;&#x2009;78&#x2009;ps (SSC), 91&#x2009;&#xb1;&#x2009;64&#x2009;ps (LSC), 27&#x2009;&#xb1;&#x2009;18&#x2009;nm (PEW) in iRORA and by 227&#x2009;&#xb1;&#x2009;112&#x2009;ps (SSC), 167&#x2009;&#xb1;&#x2009;81&#x2009;ps (LSC), and 54&#x2009;&#xb1;&#x2009;17&#x2009;nm (PEW) in cRORA. 37% of iRORA and 24% of cRORA were hyperautofluorescent in SSC. Persistent sub-RPE-BL material in MA was newly found as a hyperautofluorescent entity with lifetimes considerably longer than that of drusen and RPE.<br><br>CONCLUSIONS: Despite RPE and, thus, lipofuscin are greatly absent in MA, considerable FAF, preferably at short wavelengths, was found in those lesions. Drusen, persistent sub-RPE-BL material, basal laminar deposits, persistent activated RPE, and sclera were identified as putative sources of this fluorescence. FLIO can help to characterize respective fluorophores.},
}
@article {pmid39176054,
year = {2023},
author = {Zhang, H and Heinke, A and Galang, CMB and Deussen, DN and Wen, B and Bartsch, DG and Freeman, WR and Nguyen, TQ and An, C},
title = {Robust AMD Stage Grading with Exclusively OCTA Modality Leveraging 3D Volume.},
journal = {... IEEE International Conference on Computer Vision workshops. IEEE International Conference on Computer Vision},
volume = {2023},
number = {},
pages = {2403-2412},
pmid = {39176054},
issn = {2473-9944},
support = {R01 EY033847/EY/NEI NIH HHS/United States ; },
abstract = {Age-related Macular Degeneration (AMD) is a degenerative eye disease that causes central vision loss. Optical Coherence Tomography Angiography (OCTA) is an emerging imaging modality that aids in the diagnosis of AMD by displaying the pathogenic vessels in the subretinal space. In this paper, we investigate the effectiveness of OCTA from the view of deep classifiers. To the best of our knowledge, this is the first study that solely uses OCTA for AMD stage grading. By developing a 2D classifier based on OCTA projections, we identify that segmentation errors in retinal layers significantly affect the accuracy of classification. To address this issue, we propose analyzing 3D OCTA volumes directly using a 2D convolutional neural network trained with additional projection supervision. Our experimental results show that we achieve over 80% accuracy on a four-stage grading task on both error-free and error-prone test sets, which is significantly higher than 60%, the accuracy of human experts. This demonstrates that OCTA provides sufficient information for AMD stage grading and the proposed 3D volume analyzer is more robust when dealing with OCTA data with segmentation errors.},
}
@article {pmid39175388,
year = {2024},
author = {Huang, C and Channa, R and Zhang, AY},
title = {Cataract surgery decreases risk of falls in elderly patients with comorbid age-related macular degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {8},
pages = {888-890},
pmid = {39175388},
issn = {1442-9071},
support = {T35 AG038047/AG/NIA NIH HHS/United States ; NIH 2-T35-AG038047/AG/NIA NIH HHS/United States ; },
}
@article {pmid39174817,
year = {2025},
author = {Sadeghi, E and Vupparaboina, SC and Bollepalli, SC and Vupparaboina, KK and Agarwal, K and Sahel, JA and Eller, AW and Chhablani, J},
title = {Incidence and risk factors of fellow-eyes wet conversion in unilateral neovascular age-related macular degeneration over 15-year follow-up.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {1},
pages = {77-86},
pmid = {39174817},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Follow-Up Studies ; Incidence ; *Wet Macular Degeneration/epidemiology/diagnosis/drug therapy ; Risk Factors ; *Visual Acuity ; Aged ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Time Factors ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Disease Progression ; Middle Aged ; *Macula Lutea/pathology ; Ranibizumab/administration &amp; dosage ; },
abstract = {PURPOSE: Incidence and risk factors of fellow eye wet conversion in unilateral neovascular age-related macular degeneration (nAMD) over 15-years follow-up.<br><br>METHODS: This retrospective study reviewed 593 unilateral nAMD patients with a minimum of five years up to 15&#xa0;years of follow-up. The demographic data, visual acuity, fellow eye nAMD conversion rate, and the number of anti-vascular endothelial growth factor (anti-VEGF) injections in the primary eye were evaluated. Also, the nAMD-converted fellow eyes were divided into two groups based on the time of conversion (less and more than two years from the first injection in the primary eye). Based on the data types, the T-test, Chi-square, and Mann-Whitney U test were used to analyze.<br><br>RESULTS: The total cases were 593 patients, and 248 eyes (41.82%) converted to nAMD in the mean interval of 34.92&#x2009;&#xb1;&#x2009;30.62&#xa0;months. The males exhibited a predisposition to wet conversion at 2.54&#xa0;years earlier than their female counterparts (P&#x2009;=&#x2009;0.025). In all the converted fellow eyes, the mean age was 2.3&#xa0;years higher at presentation in the group who converted within two years of follow-up in compared to eyes that converted after two years (79.82&#x2009;&#xb1;&#x2009;8.64 vs 77.51&#x2009;&#xb1;&#x2009;8.5&#xa0;years, P&#x2009;=&#x2009;0.035). Additionally, eyes converting within two years had a mean baseline LogMAR visual acuity of 0.44&#x2009;&#xb1;&#x2009;0.47, compared to 0.32&#x2009;&#xb1;&#x2009;0.41 for conversions after two years (P&#x2009;=&#x2009;0.014).<br><br>CONCLUSION: This study reported that males showed a predisposition to fellow eye nAMD conversion at an earlier age. Additionally, there was a trend of faster fellow eye nAMD conversion in individuals with higher age and lower baseline visual acuity.<br><br>KEY MESSAGES: What is known &#x2022; Certain risk factors may make the fellow eye of neovascular age-related macular degeneration (nAMD) more likely to progress to wet conversion. &#x2022; Identifying these risk factors for fellow eye wet conversion can help prevent it, potentially preserving the patient's vision quality for a longer duration. &#x2022; The studies on the incidence of wet conversion in the fellow eye have yielded controversial results. What is new &#x2022; During the 15-year follow-up period, nearly half (47.58%) of the fellow eyes that underwent wet conversion did so within the initial two years following the wet conversion of the first eye. &#x2022; Males showed a predisposition to fellow eye nAMD conversion at an earlier age. &#x2022; There was a trend of faster fellow eye nAMD conversion in individuals with higher age and lower baseline visual acuity.},
}
@article {pmid39173893,
year = {2024},
author = {Wen, C and Yu, X and Zhu, J and Zeng, J and Kuang, X and Zhang, Y and Tang, S and Zhang, Q and Yan, J and Shen, H},
title = {Gastrodin ameliorates oxidative stress-induced RPE damage by facilitating autophagy and phagocytosis through PPARα-TFEB/CD36 signal pathway.},
journal = {Free radical biology &amp; medicine},
volume = {224},
number = {},
pages = {103-116},
doi = {10.1016/j.freeradbiomed.2024.08.023},
pmid = {39173893},
issn = {1873-4596},
mesh = {Animals ; *Oxidative Stress/drug effects ; Mice ; *Autophagy/drug effects ; *Glucosides/pharmacology ; *Phagocytosis/drug effects ; *PPAR alpha/metabolism/genetics ; *Signal Transduction/drug effects ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/genetics ; *Benzyl Alcohols/pharmacology ; *CD36 Antigens/metabolism/genetics ; Macular Degeneration/drug therapy/metabolism/pathology ; Aldehydes/metabolism/pharmacology ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; Male ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly, is primarily characterized by the degeneration of the retinal pigment epithelium (RPE). However, effective therapeutic options for dry AMD are currently lacking, necessitating further exploration into preventive and pharmaceutical interventions. This study aimed to investigate the protective effects of gastrodin on RPE cells exposed to oxidative stress. We constructed an in vitro oxidative stress model of 4-hydroxynonenal (4-HNE) and performed RNA-seq, and demonstrated the protective effect of gastrodin through mouse experiments. Our findings reveal that gastrodin can inhibit 4-HNE-induced oxidative stress, effectively improving the mitochondrial and lysosomal dysfunction of RPE cells. We further elucidated that gastrodin promotes autophagy and phagocytosis through activating the PPARα-TFEB/CD36 signaling pathway. Interestingly, these outcomes were corroborated in a mouse model, in which gastrodin maintained retinal integrity and reduced RPE disorganization and degeneration under oxidative stress. The accumulation of LC3B and SQSTM1 in mouse RPE-choroid was also reduced. Moreover, activating PPARα and downstream pathways to restore autophagy and phagocytosis, thereby countering RPE injury from oxidative stress. In conclusion, this study demonstrated that gastrodin maintains the normal function of RPE cells by reducing oxidative stress, enhancing their phagocytic function, and restoring the level of autophagic flow. These findings suggest that gastrodin is a novel formulation with potential applications in the development of AMD disease.},
}
@article {pmid39172949,
year = {2024},
author = {Pozzo Giuffrida, F and Nassisi, M and de Sanctis, L and Milella, P and Malerba, A and Mapelli, C and Dell'Arti, L and Casaluci, M and Romano, F and Invernizzi, A and Staurenghi, G and Viola, F},
title = {TEN-YEAR FOLLOW-UP OF FELLOW EYES IN PATIENTS WITH UNILATERAL NAIVE EXUDATIVE AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {12},
pages = {2049-2056},
pmid = {39172949},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Follow-Up Studies ; Aged ; *Wet Macular Degeneration/diagnosis ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Disease Progression ; *Visual Acuity/physiology ; Aged, 80 and over ; Risk Factors ; Time Factors ; Middle Aged ; Retinal Pigment Epithelium/pathology ; Fundus Oculi ; },
abstract = {PURPOSE: To determine the 10-year morphologic outcomes and identify potential risk factors of exudative age-related macular degeneration (AMD) in the fellow eyes (FEs) in patients with naive exudative AMD.<br><br>METHODS: Data from 100 patients were retrospectively reviewed. Baseline macular neovascularization (MNV) type in the exudative AMD eye and presence of drusen, intraretinal hyperreflective foci, nonfoveal incomplete retinal pigment epithelium and outer retinal atrophy, central retinal thickness, and subfoveal choroidal thickness in the FEs were analyzed as biomarkers for progression in the second eye.<br><br>RESULTS: Fifty-four patients developed exudative AMD in the FE at the end of the follow-up. Subjects with Type 2 and Type 3 macular neovascularization in the exudative AMD eye had a higher risk of exudative AMD in the FE (hazard ratio [HR] = 3.365; P = 0.039 and HR = 3.801; P = 0.037). Fellow eyes with drusen (large HR = 6.938, P = 0.001; cuticular HR = 6.937, P < 0.0001; subretinal drusenoid deposits HR = 13.678, P < 0.0001) and intraretinal hyperreflective foci (HR = 1.853, P = 0.041) were also at higher risk. Seven patients were legally blind by the end of the follow-up.<br><br>CONCLUSION: The rate of exudative AMD in the FE was 54% 10 years after the diagnosis in the exudative eye. The FE of patients with Type 2 and Type 3 macular neovascularization was at high risk of early progression. Drusen and intraretinal hyperreflective foci were also significant risk factors for macular neovascularization development.},
}
@article {pmid39172473,
year = {2024},
author = {Sherman, E and Niziol, LM and Hicks, PM and Johnson-Griggs, M and Elam, AR and Woodward, MA and Bicket, AK and Wood, SD and John, D and Johnson, L and Kershaw, M and Zhang, J and Zhang, A and Musch, DC and Newman-Casey, PA},
title = {A Screening Strategy to Mitigate Vision Impairment by Engaging Adults Who Underuse Eye Care Services.},
journal = {JAMA ophthalmology},
volume = {142},
number = {10},
pages = {909-916},
pmid = {39172473},
issn = {2168-6173},
mesh = {Humans ; Cross-Sectional Studies ; Male ; Middle Aged ; Female ; Aged ; Adult ; *Vision Screening ; Mass Screening ; Vision Disorders/diagnosis ; Telemedicine ; Eye Diseases/diagnosis ; Michigan ; Risk Factors ; Patient Acceptance of Health Care/statistics &amp; numerical data/ethnology ; },
abstract = {IMPORTANCE: Underuse of eye care services leads to underdiagnosed and undertreated eye disease.<br><br>OBJECTIVE: To assess the reasons for underuse of eye care and whether a novel, free eye disease screening program is engaging adults who are both at high risk of eye disease and were underusing eye care services.<br><br>In a population-based cross-sectional study, adult participants from the first year of the Michigan Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (MI-SIGHT) Program were included. The participants were recruited from primary care clinics serving 2 low-income communities. Recruitment occurred between June 28, 2020 and June 27, 2021 at the free clinic, and between January 27, 2021 and January 26, 2022 at a federally qualified health clinic. Data were analyzed from December 7, 2022, to May 29, 2024. Participants received comprehensive eye disease screening and completed surveys assessing health and prior eye care use. Risk factors for eye disease included age 65 years and older, diabetes, personal or family history of eye disease, and self-identifying as Black or African American individuals who were aged 50 years or older. Underuse of eye care was defined as no eye examination in 2 or more years.<br><br>MAIN OUTCOMES AND MEASURES: Percentage of participants who were at high risk of eye disease and underused eye care services before accessing this program.<br><br>RESULTS: A total of 1171 MI-SIGHT participants were a mean (SD) age of 55 (14.5) years; 437 (38%) identified as male; 591 (54%) self-identified as Black or African American, 101 (10%) as Hispanic or Latino, and 371 (34%) as White; 492 (43%) had high school education or less, and 696 (70%) reported an annual household income of less than $30&#x202f;000. Characteristics of participants reporting not having had an eye examination in 2 years or more included 23% (n&#x2009;=&#x2009;151) of participants 65 years and over, 33% (n&#x2009;=&#x2009;214) of participants who self-reported diabetes, 25% (n&#x2009;=&#x2009;130) of participants reporting a family history of glaucoma, 3% (n&#x2009;=&#x2009;14) of those with self-reported glaucoma; and 33% (n&#x2009;=&#x2009;202) of Black or African-American participants aged 50 years and older. In participants who reported not having had an eye examination in 2 or more years, 21% (n&#x2009;=&#x2009;137) screened positive for glaucoma, 20% (n&#x2009;=&#x2009;129) for cataract, 6% (n&#x2009;=&#x2009;38) for diabetic retinopathy, and 1% (n&#x2009;=&#x2009;9) for age-related macular degeneration. Reported reasons for why participants had not had an eye examination included no insurance (175 of 627 [28%]), no reason to go (no problem) (135 of 627 [22%]), and cost of eye examination (101 of 627 [16%]).<br><br>CONCLUSIONS AND RELEVANCE: The findings of this study suggest that placing eye disease detection programs in primary care clinics in underserved areas may improve eye disease detection and treatment, possibly mitigating needless vision loss in the US.},
}
@article {pmid39172225,
year = {2024},
author = {Bouaziz, M and Ferrone, PJ},
title = {Serous-Exudative Detachment and Progressive Macular Degeneration in a Patient With Kabuki and Marfan Syndrome.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {9},
pages = {541-544},
doi = {10.3928/23258160-20240624-01},
pmid = {39172225},
issn = {2325-8179},
mesh = {Humans ; *Marfan Syndrome/complications/diagnosis ; *Retinal Detachment/diagnosis/etiology ; *Macular Degeneration/diagnosis/etiology/complications ; *Tomography, Optical Coherence/methods ; Hematologic Diseases/diagnosis/complications ; Vestibular Diseases/diagnosis/etiology ; Fluorescein Angiography/methods ; Abnormalities, Multiple/diagnosis ; Face/abnormalities ; Visual Acuity ; Female ; Male ; Fundus Oculi ; Disease Progression ; },
abstract = {To our knowledge, this is the first report of a patient with both genetically confirmed Kabuki and Marfan syndrome demonstrating a perifoveal macular degeneration in one eye. Progressive loss of the outer retinal layers was captured and demonstrated with spectral-domain optical coherence tomography imaging. Fundus autofluorescence imaging revealed perifoveal hypoautofluorescence. The patient had initially presented with a spontaneously resolved serous-exudative retinal detachment associated with tortuous retinal vasculature and preretinal proliferative vitreoretinopathy in the other eye. Prior to presentation, the patient had an ocular history of bilateral ectopia lentis treated with crystalline lens removal and placement of iris-claw intraocular lenses. [Ophthalmic Surg Lasers Imaging Retina 2024;55:541-544.].},
}
@article {pmid39170441,
year = {2024},
author = {Duca, S and Nikoi, ND and Berrow, M and Barber, L and Slope, LN and Peacock, AFA and de Cogan, F},
title = {Oligoarginine peptide structure and its effect on cell penetration in ocular drug delivery.},
journal = {Heliyon},
volume = {10},
number = {15},
pages = {e35109},
pmid = {39170441},
issn = {2405-8440},
abstract = {Oligoarginine cell-penetrating peptides (CPPs) are short peptides that can enhance drug delivery into cells and are of particular interest in ocular topical formulations for age-related macular degeneration (AMD) treatments. The length and structural characteristics of these peptides are considered crucial for drug delivery. This study investigates how oligoarginine length (Rn) affects their penetration mechanism, drug delivery capabilities, and antimicrobial properties, providing insights into their potential roles in AMD treatment delivery. In this study, oligoarginine peptides showed limited pore-forming abilities in a carboxyfluorescein-containing liposomal model, with R9 being the only oligoarginine length recording a significant pore-formation level. Their antibacterial efficacy depended on both the CPP length and bacterial class, with longer peptides exhibiting stronger antibacterial effects. Importantly, oligoarginine was found nontoxic to relevant mammalian cells for ocular delivery. The membrane translocation abilities of oligoarginine were consistent regardless of cargo presence. Additionally, cargo delivery by oligoarginine across in vitro cellular models for ocular delivery was dependent on peptide length and cell type, with longer chains being more effective at cargo uptake in a corneal epithelium cell line, and with shorter chains proving more effective for cargo delivery in a retinal epithelium cell line. This proposes that the chain length of oligoarginine could be used as a strategic tool in the formulation process to selectively target distinct regions of the eye. Overall, this study expands our understanding of how oligoarginine CPPs can be applied as penetration enhancers to improve the delivery of therapeutics in an ocular topical formulation within the clinical context of AMD.},
}
@article {pmid39169293,
year = {2024},
author = {Kim, JH and Kim, JW and Kim, CG},
title = {Importance of optical coherence tomography raster scans in early detection of active fellow-eye neovascularization in unilateral neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {359},
pmid = {39169293},
issn = {1471-2415},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; Aged ; *Wet Macular Degeneration/diagnosis ; Aged, 80 and over ; Visual Acuity ; Choroidal Neovascularization/diagnosis/diagnostic imaging ; Early Diagnosis ; Fluorescein Angiography/methods ; Risk Factors ; Follow-Up Studies ; Middle Aged ; },
abstract = {PURPOSE: To investigate the incidence of and risk factors for failure of detection of active fellow-eye neovascularization on optical coherence tomography(OCT) crosshair scans in patients with unilateral neovascular age-related macular degeneration(AMD).<br><br>METHODS: In this retrospective study, patients who experienced the development of active neovascularization in the fellow eye during the follow-up period were included(n&#x2009;=&#x2009;75). Cases in which the neovascularization in the fellow eye could be identified solely through crosshair scans were defined as the crosshair scan detection group(n&#x2009;=&#x2009;63). Cases in which the aforementioned findings could not be identified through crosshair scans but could be identified through raster scans were defined as the raster scan detection group(n&#x2009;=&#x2009;12). The factors were compared between the two groups. Risk factors related to undetected neovascularization on crosshair scans were additionally identified.<br><br>RESULTS: Active fellow-eye neovascularization, was not detected on OCT crosshair scans in 12 cases(16.0%) but was identified on raster scans in all cases. There was a significant difference in the proportion of neovascularization types between the crosshair scan detection group and the raster scan detection group(P&#x2009;=&#x2009;0.023). Among the 35 fellow-eye neovascularization cases in patients with type 3 macular neovascularization(MNV), 10(28.6%) were not detected on crosshair scans. Multivariate analysis revealed a significantly higher risk for undetectable fellow-eye neovascularization on crosshair scans in patients with type 3 MNV than in those with typical neovascular AMD(P&#x2009;=&#x2009;0.037,&#x3b2;&#x2009;=&#x2009;9.600).<br><br>CONCLUSIONS: Our findings suggest the need for routine OCT raster scans during fellow-eye examinations in patients with unilateral neovascular AMD, particularly when the first-affected eye is diagnosed with type 3 MNV.},
}
@article {pmid39169055,
year = {2024},
author = {Nguyen, VP and Karoukis, AJ and Hu, J and Wei, Z and Yang, D and Fahim, AT and Wang, X and Paulus, YM},
title = {Selective nanosecond laser removal of retinal pigment epithelium for cell therapy.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {19457},
pmid = {39169055},
issn = {2045-2322},
support = {R01 EY034325/EY/NEI NIH HHS/United States ; R41 EY031219/EY/NEI NIH HHS/United States ; K08 EY027458/EY/NEI NIH HHS/United States ; R42 EY035582/EY/NEI NIH HHS/United States ; YMP:1K08EY027458/EY/NEI NIH HHS/United States ; R01 EY033000/EY/NEI NIH HHS/United States ; P30 EY007003/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Pigment Epithelium/cytology ; Animals ; Rabbits ; Humans ; Induced Pluripotent Stem Cells/cytology ; Cell- and Tissue-Based Therapy/methods ; Tomography, Optical Coherence ; Laser Therapy/methods ; Lasers ; Cell Differentiation ; Fluorescein Angiography ; },
abstract = {Retinal pigment epithelial (RPE) cells play a crucial role in the health of the retina, and their dysfunction is associated with various ocular diseases. The transplantation of RPE cells has been proposed as a potential treatment for numerous degenerative diseases, including geographic atrophy from macular degeneration. However, current models to induce RPE damage in animal models prior to transplantation involve mechanical scraping, chemical administration, or laser photocoagulation techniques, which can damage the overlying neurosensory retina. This study aims to investigate the feasibility and efficacy of nanosecond duration laser treatment to safely remove large areas of RPE cells without causing damage to the adjacent tissue or affecting the retinal architecture. Twelve pigmented rabbits were treated with a nanosecond laser on each eye at a laser energy ranging from 200 to 800 nJ with a treated area of 5 × 5 mm[2]. Human induced pluripotent stem cells-differentiated to RPE (hiPSC-RPE) cells labeled with indocyanine green (ICG), an FDA approved dye, were transplanted subretinally into the damaged RPE areas at day 14 post-laser treatment. The RPE atrophy and hiPSC-RPE cell survival was evaluated and monitored over a period of 14 days using color photography, fluorescein angiography (FA), photoacoustic microscopy (PAM), and optical coherence tomography (OCT) imaging. All treated eyes demonstrated focal RPE loss with a success rate of 100%. The injured RPE layers and the transplanted hiPSC-RPE cells were visualized in three dimensions using PAM and OCT. By performing PAM at an optical wavelength of 700 nm, the location of hiPSC-RPE cells were identified and distinguished from the surrounding RPE cells, and the induced PA signal increased up to 18 times. Immunohistochemistry results confirmed the grafted hiPSC-RPE replaced regions of RPE damage. This novel technique has the potential to serve as an animal model of RPE degeneration, to improve models of RPE transplantation, and may help accelerate translation of this therapeutic strategy for clinical use.},
}
@article {pmid39168286,
year = {2024},
author = {Faizi, HS and Nasiri, MI and Wu, Y and Mishra, D and Donnelly, RF and Minhas, MU and Vora, LK and Singh Thakur, RR},
title = {Deferasirox nanosuspension loaded dissolving microneedles for ocular drug delivery.},
journal = {International journal of pharmaceutics},
volume = {664},
number = {},
pages = {124614},
doi = {10.1016/j.ijpharm.2024.124614},
pmid = {39168286},
issn = {1873-3476},
mesh = {*Deferasirox/administration &amp; dosage/pharmacokinetics ; *Needles ; Animals ; *Drug Delivery Systems ; Swine ; *Iron Chelating Agents/administration &amp; dosage ; Solubility ; Suspensions ; Sclera/metabolism ; Humans ; Retinal Pigment Epithelium/drug effects ; Nanoparticles/administration &amp; dosage ; Cell Survival/drug effects ; Cell Line ; Administration, Ophthalmic ; Microinjections/methods ; Drug Stability ; Tomography, Optical Coherence ; },
abstract = {Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner.},
}
@article {pmid39167570,
year = {2024},
author = {Song, JS and Kim, MS and Joo, K and Park, SJ and Woo, SJ and Park, KH},
title = {INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND POOR VISUAL ACUITY.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {9},
pages = {1486-1494},
doi = {10.1097/IAE.0000000000004154},
pmid = {39167570},
issn = {1539-2864},
support = {2020R1A2C2011189//National Research Foundation of Korea/ ; SNUBH-02 to 2021-0021//Seoul National University Bundang Hospital/ ; },
mesh = {Humans ; *Visual Acuity/physiology ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Retrospective Studies ; Male ; Female ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Ranibizumab/administration &amp; dosage ; *Tomography, Optical Coherence ; Aged, 80 and over ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Fluorescein Angiography ; Follow-Up Studies ; },
abstract = {PURPOSE: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity.<br><br>METHODS: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of &#x2264;20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of &#x2264;4 months or not.<br><br>RESULTS: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group.<br><br>CONCLUSION: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.},
}
@article {pmid39167569,
year = {2024},
author = {Huang, RS and Mihalache, A and Popovic, MM and Munn, C and Melo, IM and Pecaku, A and Friedman, A and Wong, DT and Muni, RH},
title = {ARTIFICIAL INTELLIGENCE-ENHANCED ANALYSIS OF RETINAL VASCULATURE IN AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {9},
pages = {1478-1485},
doi = {10.1097/IAE.0000000000004159},
pmid = {39167569},
issn = {1539-2864},
mesh = {Humans ; Male ; Female ; *Tomography, Optical Coherence/methods ; Aged ; *Fluorescein Angiography/methods ; Prospective Studies ; *Artificial Intelligence ; *Retinal Vessels/diagnostic imaging/pathology ; *Wet Macular Degeneration/diagnosis/physiopathology ; Middle Aged ; *Visual Acuity/physiology ; Fundus Oculi ; Aged, 80 and over ; Blood-Retinal Barrier ; },
abstract = {PURPOSE: To investigate associations between quantitative vascular measurements derived from intravenous fluorescein angiography (IVFA) and baseline characteristics on optical coherence tomography (OCT) in neovascular age-related macular degeneration (nAMD) patients.<br><br>METHODS: The authors prospectively recruited patients with active choroidal neovascularization secondary to AMD over 50 years old, presenting to a single center in Toronto, Canada from 2017 to 2023. Ultra-widefield IVFA images were processed using the artificial intelligence RETICAD FAassist system to extract quantitative information on blood flow, perfusion, and blood-retinal-barrier (BRB) permeability. Associations between IVFA parameters with functional and anatomical outcomes were examined using univariable and multivariable regression models.<br><br>RESULTS: Eighty-one nAMD eyes and seven healthy control eyes were included. Compared with healthy controls, BRB permeability in the central and peripheral retina was significantly higher in nAMD patients (P < 0.001). On univariable analysis, BRB permeability measured centrally was significantly associated with central macular thickness (P = 0.035), whereas perfusion and blood flow measured centrally were significantly associated with macular volume (P = 0.043 and 0.037, respectively). On multivariable analysis, BRB permeability remained significantly associated with central macular thickness (P = 0.026).<br><br>CONCLUSION: Central BRB permeability measured on IVFA was significantly associated with baseline central macular thickness in nAMD patients. Future work should longitudinally explore associations between IVFA parameters and clinical characteristics in diverse nAMD populations.},
}
@article {pmid39167547,
year = {2024},
author = {Durak, S and Sutova, HE and Ceylan, R and Aciksari, A and Yetisgin, AA and Onder Tokuc, E and Kutlu, O and Karabas, VL and Cetinel, S},
title = {A Nanogel Formulation of Anti-VEGF Peptide for Ocular Neovascularization Treatment.},
journal = {ACS applied bio materials},
volume = {7},
number = {9},
pages = {6001-6013},
doi = {10.1021/acsabm.4c00585},
pmid = {39167547},
issn = {2576-6422},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/metabolism/chemistry ; Animals ; *Nanogels/chemistry ; Particle Size ; Biocompatible Materials/chemistry/pharmacology ; Materials Testing ; Cell Proliferation/drug effects ; Peptides/chemistry/pharmacology/administration &amp; dosage ; Human Umbilical Vein Endothelial Cells ; Angiogenesis Inhibitors/chemistry/pharmacology/administration &amp; dosage ; Macular Degeneration/drug therapy/pathology/metabolism ; Polyethyleneimine/chemistry ; Mice ; Cell Line ; },
abstract = {Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. In vivo experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.},
}
@article {pmid39167400,
year = {2024},
author = {Borella, Y and Danielsen, N and Markle, EM and Snyder, VC and Lee, DMW and Zhang, M and Eller, AW and Chhablani, J and Paques, M and Rossi, EA},
title = {Are the Hypo-Reflective Clumps Associated With Age-Related Macular Degeneration in Adaptive Optics Ophthalmoscopy Autofluorescent?.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {10},
pages = {28},
pmid = {39167400},
issn = {1552-5783},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; R01 EY030517/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Ophthalmoscopy/methods ; Female ; Aged ; Male ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Aged, 80 and over ; *Macular Degeneration/diagnosis ; Optical Imaging/methods ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: Hypo-reflective clumps (HRCs) are structures associated with age-related macular degeneration (AMD) that were identified using flood-illumination adaptive optics ophthalmoscopy (FIAO) and hypothesized to be either macrophages that have accumulated melanin through the phagocytosis of retinal pigmented epithelial (RPE) cell organelles or transdifferentiated RPE cells. HRCs may be autofluorescent (AF) in the near infrared (NIR) but clinical NIR autofluorescence imaging lacks the resolution to answer this question definitively. Here, we used near infrared autofluorescence (NIRAF) imaging in fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to determine whether HRCs are AF.<br><br>METHODS: Patients with AMD and HRCs underwent imaging with FIAO, optical coherence tomography (OCT), and multi-modal AOSLO (confocal, NIRAF, and non-confocal multi-offset detection using a fiber bundle). HRCs were segmented on FIAO and images, co-registered across modalities, and HRC morphometry and AF were quantified.<br><br>RESULTS: Eight patients participated (mean age = 79 years, standard deviation [SD] = 5.7, range = 69-89 years, and 5 female patients). Most HRCs (86%, n = 153/178) were autofluorescent on AOSLO. HRC AF signal varied but most uniformly dark HRCs on FIAO showed corresponding AF on AOSLO, whereas heterogeneous HRCs showed a smaller AF area or no AF.<br><br>CONCLUSIONS: These findings are consistent with the hypothesis that HRCs contain AF RPE organelles. A small proportion of HRCs were not AF; these may represent macrophages that have not yet accumulated enough organelles to become AF. HRCs may have clinical significance but further study is needed to understand the interplay among HRCs, RPE cells, and macrophages, and their relationship to geographic atrophy (GA) progression in AMD.},
}
@article {pmid39167170,
year = {2025},
author = {Das, A and Shahriar, TG and Zehravi, M and Sweilam, SH and Alshehri, MA and Ahmad, I and Nafady, MH and Emran, TB},
title = {Clinical management of eye diseases: carotenoids and their nanoformulations as choice of therapeutics.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {398},
number = {1},
pages = {329-349},
pmid = {39167170},
issn = {1432-1912},
mesh = {Humans ; Animals ; *Eye Diseases/drug therapy ; *Nanoparticles ; *Antioxidants/administration &amp; dosage/therapeutic use ; *Carotenoids/administration &amp; dosage/therapeutic use ; *Anti-Inflammatory Agents/administration &amp; dosage ; Drug Compounding ; },
abstract = {Eye diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR), impose a substantial health cost on a worldwide scale. Carotenoids have emerged as intriguing candidates for pharmacological treatment of various disorders. Their therapeutic effectiveness, however, is hindered by poor solubility and vulnerability to degradation. Nanocarriers, such as nanoparticles, liposomes, and micelles, provide a transformational way to overcome these limits. This review explores the pharmacological potential of carotenoids, namely lutein, zeaxanthin, and astaxanthin, to treat several ocular disorders. The main emphasis is on their anti-inflammatory and antioxidant actions, which help to counteract inflammation and oxidative stress, crucial factors in the development of AMD and DR. The review evaluates the significant benefits of nano-formulated carotenoids, such as improved bioavailability, higher cellular absorption, precise administration to particular ocular tissues, and greater biostability, which make them superior to conventional carotenoids. Some clinical studies on the beneficial properties of carotenoids in eye diseases are discussed. Furthermore, safety and regulatory concerns are also taken into account. Ultimately, carotenoids, especially when created in their nano form, have significant potential for safeguarding eyesight and enhancing the overall well-being of several individuals afflicted with vision-endangering eye diseases.},
}
@article {pmid39164928,
year = {2024},
author = {Nguyen, AV and Deineka, VI and Burzhinskaya, TG and Blinova, IP and Deineka, LA and Vu, ATN},
title = {Determination of xanthophylls in egg yolk using a combination of spectrophotometric and diol phase high-performance liquid chromatography methods.},
journal = {Journal of separation science},
volume = {47},
number = {16},
pages = {e2400125},
doi = {10.1002/jssc.202400125},
pmid = {39164928},
issn = {1615-9314},
mesh = {*Egg Yolk/chemistry ; Chromatography, High Pressure Liquid ; *Xanthophylls/analysis/chemistry ; Spectrophotometry ; Animals ; Isomerism ; },
abstract = {Normal-phase (NP) liquid chromatography is one of the most effective methods for separating isomers with sensitive structural features, including xanthophyll isomers. In this work, reverse-phase (RP) and NP liquid chromatography (LC), with silica gel and diol phase, respectively, were evaluated for the separation of xanthophyll isomers. The results showed that RP LC with monomeric C18 phase not only poorly separate all xanthophyll isomers in egg yolk but also requires additional sample preparation to eliminate triacylglycerols in egg yolk. The diol phase of NP-LC provided the highest efficiency for separating lutein, zeaxanthin, and their cis-isomers with isocratic separation using mobile phases consisting of n-hexane and polar modifiers (such as acetone, methyl tert-butyl ether, or ethyl acetate). To determine the xanthophyll content, peak areas from LC and total absorbance from spectrophotometry measurements were used. The approach was applied to analyze the xanthophylls of nine commercial egg samples. The results revealed that five out of nine analyzed samples contained a high level of canthaxanthin, which contributes to color enhancement but not to prevent age-related macular degeneration. Together, it shows that NP LC with diol phase combined with spectrophotometry is a powerful tool to monitor xanthophylls in eggs.},
}
@article {pmid39164678,
year = {2024},
author = {Bonilla-Escobar, FJ and Eibel, MR and Le, L and Gallagher, DS and Waxman, EL},
title = {Follow-up in a point-of-care diabetic retinopathy program in Pittsburgh: a non-concurrent retrospective cohort study.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {356},
pmid = {39164678},
issn = {1471-2415},
mesh = {Humans ; Retrospective Studies ; *Diabetic Retinopathy/diagnosis/epidemiology ; Male ; Middle Aged ; Female ; Follow-Up Studies ; Aged ; Pennsylvania/epidemiology ; Point-of-Care Systems ; Adult ; },
abstract = {BACKGROUND: The Point-of-Care Diabetic Retinopathy Examination Program (POCDREP) was initiated in 2015 at the University of Pittsburgh/UPMC in response to low diabetic retinopathy (DR) examination rates, a condition affecting a quarter of people with diabetes mellitus (PwDM) and leading to blindness. Early detection and treatment are critical with DR prevalence projected to triple by 2050. Approximately, half of PwDM in the U.S. undergo yearly examinations, and there are reported varying follow-up rates with eye care professionals, with limited data on the factors influencing these trends. POCDREP aimed to address screening and follow-up gap, partnering with diverse healthcare entities, including primary care sites, free clinics, and federally qualified health centers.<br><br>METHODS: A non-concurrent retrospective cohort study spanning 2015-2018 examined data using electronic health records of patients who underwent retinal imaging. Imaging was performed using 31 cameras across various settings, with results interpreted by ophthalmologists. Follow-up recommendations were made for cases with vision-threatening DR (VTDR), incidental findings, or indeterminate results. Factors influencing follow-up were analyzed, including demographic, clinical, and imaging-related variables. We assessed the findings at follow-up of patients with indeterminate results.<br><br>RESULTS: Out of 7,733 examinations (6,242 patients), 32.25% were recommended for follow-up. Among these,&#xa0;5.57% were classified as having VTDR, 14.34% had&#xa0;other ocular findings such as&#xa0;suspected glaucoma and age-related macular degeneration (AMD), and 12.13% were indeterminate. Of those recommended for follow-up, only 30.87% were assessed by eye care within six months. Older age, marriage, and severe DR were associated with higher odds of following up. Almost two thirds (64.35%) of the patients with indeterminate exams were found with a vision-threatening disease at follow-up.<br><br>CONCLUSION: The six-month follow-up rate was found to be suboptimal. Influential factors for follow-up included age, marital status, and the severity of diabetic retinopathy (DR). While the program successfully identified a range of ocular conditions, screening initiatives must extend beyond mere disease detection. Ensuring patient follow-up is crucial to DR preventing programs&#xa0;mission. Recommended strategies to improve follow-up adherence include education, incentives, and personalized interventions. Additional research is necessary to pinpoint modifiable factors that impact adherence and to develop targeted interventions.},
}
@article {pmid39164449,
year = {2024},
author = {Schranz, M and Bogunovic, H and Deak, G and Sadeghipour, A and Reiter, GS and Schmidt-Erfurth, U},
title = {Linking disease activity with optical coherence tomography angiography in neovascular age related macular degeneration using artificial intelligence.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {19278},
pmid = {39164449},
issn = {2045-2322},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Angiogenesis Inhibitors/therapeutic use ; *Artificial Intelligence ; Choroidal Neovascularization/diagnostic imaging/pathology ; Deep Learning ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnostic imaging/pathology ; *Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/metabolism ; Wet Macular Degeneration/diagnostic imaging/drug therapy ; },
abstract = {To investigate quantitative associations between AI-assessed disease activity and optical coherence tomography angiography (OCTA)-derived parameters in patients with neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy. OCTA and SD-OCT images obtained from multicenter, randomized study data were evaluated. A deep learning algorithm (RetInSight) was used to detect and quantify macular fluid on SD-OCT. Mixed effects models were applied to evaluate correlations between fluid volumes, macular neovascularization (MNV)-type and OCTA-derived MNV parameters; lesion size (LS) and vessel area (NVA). 230 patients were included. A significant positive correlation was observed between SRF and NVA (estimate = 199.8 nl/mm[2], p = 0.023), while a non-significant but negative correlation was found between SRF and LS (estimate = - 71.3 nl/mm[2], p = 0.126). The presence of Type I and Type II MNV was associated with significantly less intraretinal fluid (IRF) compared to Type III MNV (estimate type I:- 52.1 nl, p = 0.019; estimate type II:- 51.7 nl, p = 0.021). A significant correlation was observed between pigment epithelial detachment (PED) and the interaction between NVA and LS (estimate:28.97 nl/mm[2]; p = 0.012). Residual IRF at week 12 significantly correlated to baseline NVA (estimate:38.1 nl/mm[2]; p = 0.015) and LS (estimate:- 22.6 nl/mm[2]; p = 0.012). Fluid in different compartments demonstrated disparate associations with MNV OCTA features. While IRF at baseline was most pronounced in type III MNV, residual IRF was driven by neovascular MNV characteristics. Greater NVA in proportion to LS was associated with higher amounts of SRF and PED. The correlation between these parameters may represent MNV maturation and can be used as a biomarker for resolution of disease activity. AI-based OCT analysis allows for a deeper understanding of neovascular disease in AMD and the potential to adjust therapeutic strategies to optimize outcomes through precision medicine.},
}
@article {pmid39164445,
year = {2024},
author = {Pang, S and Zou, B and Xiao, X and Peng, Q and Yan, J and Zhang, W and Yue, K},
title = {A novel approach for automatic classification of macular degeneration OCT images.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {19285},
pmid = {39164445},
issn = {2045-2322},
support = {A2023048//2023 Hunan Traditional Chinese Medicine Scientific Research Project/ ; 23A0273//Research Foundation of Education Bureau of Hunan Province, China/ ; 2021JJ30173//Hunan Provincial Natural Science Foundation of China/ ; },
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/classification/pathology ; *Tomography, Optical Coherence/methods ; *Deep Learning ; *Neural Networks, Computer ; Macular Edema/diagnostic imaging/classification/pathology ; Diabetic Retinopathy/diagnostic imaging/classification/pathology/diagnosis ; Image Processing, Computer-Assisted/methods ; },
abstract = {Age-related macular degeneration (AMD) and diabetic macular edema (DME) are significant causes of blindness worldwide. The prevalence of these diseases is steadily increasing due to population aging. Therefore, early diagnosis and prevention are crucial for effective treatment. Classification of Macular Degeneration OCT Images is a widely used method for assessing retinal lesions. However, there are two main challenges in OCT image classification: incomplete image feature extraction and lack of prominence in important positional features. To address these challenges, we proposed a deep learning neural network model called MSA-Net, which incorporates our proposed multi-scale architecture and spatial attention mechanism. Our multi-scale architecture is based on depthwise separable convolution, which ensures comprehensive feature extraction from multiple scales while minimizing the growth of model parameters. The spatial attention mechanism is aim to highlight the important positional features in the images, which emphasizes the representation of macular region features in OCT images. We test MSA-NET on the NEH dataset and the UCSD dataset, performing three-class (CNV, DURSEN, and NORMAL) and four-class (CNV, DURSEN, DME, and NORMAL) classification tasks. On the NEH dataset, the accuracy, sensitivity, and specificity are 98.1%, 97.9%, and 98.0%, respectively. After fine-tuning on the UCSD dataset, the accuracy, sensitivity, and specificity are 96.7%, 96.7%, and 98.9%, respectively. Experimental results demonstrate the excellent classification performance and generalization ability of our model compared to previous models and recent well-known OCT classification models, establishing it as a highly competitive intelligence classification approach in the field of macular degeneration.},
}
@article {pmid39163034,
year = {2024},
author = {Goerdt, L and Amjad, M and Swain, TA and McGwin, G and Clark, ME and Owsley, C and Sloan, KR and Curcio, CA and Kar, D},
title = {Extent and Topography of Subretinal Drusenoid Deposits Associate With Rod-Mediated Vision in Aging and AMD: ALSTAR2 Baseline.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {10},
pages = {25},
pmid = {39163034},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Aged ; Male ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis/physiopathology ; Middle Aged ; *Dark Adaptation/physiology ; *Retinal Rod Photoreceptor Cells/physiology/pathology ; *Macular Degeneration/physiopathology/diagnosis ; *Visual Acuity/physiology ; Aging/physiology ; Aged, 80 and over ; Fluorescein Angiography/methods ; Deep Learning ; },
abstract = {PURPOSE: In AMD, rod-mediated dark adaptation (RMDA) at 5° eccentricity is slower in eyes with subretinal drusenoid deposits (SDDs) than in eyes without. Here we quantified SDD burden using supervised deep learning for comparison to vision and photoreceptor topography.<br><br>METHODS: In persons &#x2265;60 years from the Alabama Study on Early Age-Related Macular Degeneration 2, normal, early AMD, and intermediate AMD eyes were classified by the AREDS nine-step system. A convolutional neural network was trained on 55&#xb0;-wide near-infrared reflectance images for SDD segmentation. Trained graders annotated ground truth (SDD yes/no). Predicted and true datasets agreed (Dice coefficient, 0.92). Inference was manually proofread using optical coherence tomography. The mean SDD area (mm2) was compared among diagnostic groups (linear regression) and to vision (age-adjusted Spearman correlations). Fundus autofluorescence images were used to mask large vessels in SDD maps.<br><br>RESULTS: In 428 eyes of 428 persons (normal, 218; early AMD, 120; intermediate AMD, 90), the mean SDD area differed by AMD severity (P < 0.0001): 0.16 &#xb1; 0.87 (normal), 2.48 &#xb1; 11.23 (early AMD), 11.97 &#xb1; 13.33 (intermediate AMD). Greater SDD area was associated with worse RMDA (r = 0.27; P < 0.0001), mesopic (r = -0.13; P = 0.02) and scotopic sensitivity (r = -0.17; P < 0.001). SDD topography peaked at 5&#xb0; superior, extended beyond the Early Treatment of Diabetic Retinopathy Study grid and optic nerve, then decreased.<br><br>CONCLUSIONS: SDD area is associated with degraded rod-mediated vision. RMDA 5&#xb0; (superior retina) probes where SDD is maximal, closer to the foveal center than the rod peak at 3 to 6 mm (10.4&#xb0;-20.8&#xb0;) superior and the further eccentric peak of rod:cone ratio. Topographic data imply that factors in addition to rod density influence SDD formation.},
}
@article {pmid39162906,
year = {2024},
author = {Matsumoto, H and Hoshino, J and Numaga, S and Mimura, K and Asatori, Y and Akiyama, H},
title = {Retinal vasculitis after intravitreal aflibercept 8 mg for neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {68},
number = {5},
pages = {531-537},
pmid = {39162906},
issn = {1613-2246},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Intravitreal Injections ; Female ; Male ; Retrospective Studies ; *Visual Acuity/physiology ; Aged ; *Tomography, Optical Coherence ; Aged, 80 and over ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Fluorescein Angiography ; *Retinal Vasculitis/diagnosis/drug therapy/physiopathology ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Follow-Up Studies ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; },
abstract = {PURPOSE: To evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8&#xa0;mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined.<br><br>RESULTS: BCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8&#xa0;mg (all P&#x2009;<&#x2009;0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss.<br><br>CONCLUSIONS: Intravitreal aflibercept 8&#xa0;mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis.},
}
@article {pmid39162805,
year = {2025},
author = {Zarnegar, A and Valsecchi, N and Sadeghi, E and Shah, S and Tang, A and Yagobian, S and Iannetta, D and Chhablani, J},
title = {Choroidal imaging biomarkers as predictors of conversion to exudative age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {1},
pages = {59-67},
pmid = {39162805},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; *Choroid/pathology/diagnostic imaging ; Female ; Male ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Fluorescein Angiography/methods ; Aged ; Follow-Up Studies ; Disease Progression ; Biomarkers ; Fundus Oculi ; *Visual Acuity ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Middle Aged ; Macula Lutea/pathology ; Intravitreal Injections ; },
abstract = {PURPOSE: Predicting the progression of intermediate AMD (iAMD) to neovascular AMD (nAMD) will help to identify high-risk patients and improve treatment outcomes. The present study assessed whether choroidal OCT biomarkers could predict conversion to nAMD.<br><br>METHODS: This retrospective study included patients with clinically stable iAMD who either converted to nAMD (C group) or did not convert (NC group) during one year of follow-up. OCT parameters included subfoveal choroidal thickness (SFCT), central macular thickness (CMT), Haller vascular thickness (HVT), inner choroidal thickness (ICT), and double-layer sign (DLS).<br><br>RESULTS: Of 116 total eyes, there were 37 in the NC group and 79 in the C group. Baseline SFCT was significantly lower in the C group compared to the NC group (169.0&#x2009;&#xb1;&#x2009;63.2&#xa0;&#x3bc;m vs. 218.0&#x2009;&#xb1;&#x2009;97.8&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.01). Baseline HVT and ICT were lower in the C group (105.2&#x2009;&#xb1;&#x2009;40.6&#xa0;&#x3bc;m vs. 121.0&#x2009;&#xb1;&#x2009;56.6&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.17 and 61.9&#x2009;&#xb1;&#x2009;35.5&#xa0;&#x3bc;m vs. 77.5&#x2009;&#xb1;&#x2009;41.7&#xa0;&#x3bc;m, p&#x2009;=&#x2009;0.09). HVT was decreased at all time points in the C group vs NC (p&#x2009;>&#x2009;0.05). The ICT was reduced in the C group at each time point except at conversion time (p&#x2009;>&#x2009;0.05). Of all eight eyes who presented DLS at baseline, 100% converted to nAMD (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Lower SFCT at baseline may signal conversion to nAMD within 12&#xa0;months.},
}
@article {pmid39161751,
year = {2024},
author = {Gomi, F and Iida, T and Mori, R and Horita, S and Nakamura, H and Nakajima, Y and Shiokawa, A and Takahashi, K},
title = {Phase I Study of Tivozanib Eye Drops in Healthy Volunteers and Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100553},
pmid = {39161751},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the safety, pharmacokinetics, and exploratory efficacy of tivozanib eye drops in healthy volunteers and patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: This multicenter group-sequential dose escalation phase I study consisted of a placebo-controlled double-masked study of healthy volunteers (cohorts 1 and 2) and an open-label study of patients with nAMD (cohort 3).<br><br>PARTICIPANTS: Healthy volunteers: Japanese or White men aged 20 to <50 years. Patients with nAMD with central subfield thickness (CST) &#x2265;300 &#x3bc;m and best-corrected visual acuity score &#x2265;23 letters in the study eye.<br><br>METHODS: In the single-dose cohort of healthy men (cohort 1: steps 1-5), 1 or 2 tivozanib eye drops (30 &#x3bc;L/drop, 5-minute interval; 0.5, 1.0, and 2.0 w/v%) or placebo were administered in 1 eye once. In the multiple-dose cohort of healthy men (cohort 2: steps 1-6), 1 or 2 tivozanib eye drops (0.5, 1.0, and 2.0 w/v%) or placebo were administered 3 times daily in 1 eye for 21 days. In the multiple-dose cohort of patients with nAMD (cohort 3, steps 1-3), 1 or 2 tivozanib eye drops (0.5 and 1.0 w/v%) were administered 3 times daily in 1 affected eye for 21 days.<br><br>MAIN OUTCOME MEASURES: The safety outcome measures included adverse events (AEs). The pharmacokinetic outcome was serum tivozanib concentration. Among the exploratory efficacy outcomes, CST was evaluated.<br><br>RESULTS: In total, 40, 48, and 28 participants were enrolled in cohorts 1, 2, and 3, respectively. Serious AEs did not occur in cohorts 1 to 3. The most frequent AE in multiple-dose cohorts was reversible punctate keratitis: placebo arm, 8.3% (healthy men, 1/12); tivozanib arm, 47.2% (healthy men, 17/36) and 14.3% (nAMD, 4/28). Serum tivozanib exposure increased dose-dependently and was similar in healthy men and patients with nAMD. In patients with nAMD, mean CST changes from baseline to day 22 were&#xa0;-27.6&#xa0;&#xb1;&#xa0;54.88 (0.5 w/v%; 1 drop, 3 times daily),&#xa0;-35.6&#xa0;&#xb1;&#xa0;49.64 (1.0 w/v%; 1 drop, 3 times daily), and&#xa0;-43.7&#xa0;&#xb1;&#xa0;55.19 &#x3bc;m (1.0 w/v%; 2 drops, 3 times daily).<br><br>CONCLUSIONS: Tivozanib eye drops showed a favorable safety profile in healthy Japanese and White men and Japanese patients with nAMD.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39161750,
year = {2024},
author = {Kumar, H and Guymer, RH and Hodgson, LAB and Hadoux, X and Jannaud, M and van Wijngaarden, P and Luu, CD and Wu, Z},
title = {Reticular Pseudodrusen: Impact of Their Presence and Extent on Local Rod Function in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100551},
pmid = {39161750},
issn = {2666-9145},
abstract = {PURPOSE: To understand the spatial relationship between local rod-mediated visual function and reticular pseudodrusen (RPD) in eyes with large drusen.<br><br>DESIGN: Retrospective cross-sectional study.<br><br>PARTICIPANTS: One eye with large drusen (>125 &#x3bc;m) each from 91 individuals with intermediate age-related macular degeneration, with and without RPD.<br><br>METHODS: All participants underwent dark adaptation testing using a dark-adapted chromatic perimeter, where visual sensitivities were measured over 30 minutes of dark adaptation after photobleach. The rod intercept time (RIT; a measure of dynamic rod function) and pointwise sensitivity difference (PWSD; a relative measure of rod- compared with cone-mediated function) was determined at multiple retinal locations, and their association with the overall (central 20&#xb0;&#xa0;&#xd7; 20&#xb0; region) and local (2&#xb0; diameter region centered on the location tested) extent of RPD and drusen (quantified using multimodal imaging) was examined.<br><br>MAIN OUTCOME MEASURES: Association between overall and local extent of RPD and drusen with RIT and PWSD at each retinal location tested.<br><br>RESULTS: In a multivariable analysis, delayed RIT was associated with an increasing overall (P < 0.001), but not local (P&#xa0;= 0.884), extent of RPD. In contrast, the increasing local (P < 0.001), but not overall (P&#xa0;= 0.475), extent of drusen was associated with delayed RIT. Furthermore, only an increasing overall extent of RPD (P < 0.001) was associated with reduced PWSD (or worse rod compared with cone function), but not the local extent of RPD and drusen, or overall extent of drusen (P &#x2265; 0.344).<br><br>CONCLUSIONS: Local rod-mediated function was associated with the overall, rather than local, extent of RPD in eyes with large drusen, suggesting that there may be widespread pathologic changes in eyes with RPD that account for this.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39161229,
year = {2025},
author = {Senthilkumari, S and Rajendren, A and Panneerselvam, B and Uduman, MS},
title = {Association of macular pigment optical density with plasma macular carotenoids levels and serum lipids in South Indian healthy volunteers and patients with early age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {35},
number = {2},
pages = {669-678},
doi = {10.1177/11206721241272254},
pmid = {39161229},
issn = {1724-6016},
mesh = {Humans ; Male ; Female ; *Macular Pigment/metabolism ; *Carotenoids/blood ; *Lipids/blood ; India/epidemiology ; Middle Aged ; Adult ; Healthy Volunteers ; Chromatography, High Pressure Liquid ; *Macular Degeneration/blood/epidemiology ; Aged ; *Macula Lutea/metabolism ; Lutein/blood ; },
abstract = {Purpose: The objective of the present study was to investigate the relationship between macular pigment optical density (MPOD) and plasma carotenoids [(L) and (Z)] and serum lipids in South Indian young healthy volunteers and patients with early age-related macular degeneration (AMD). Methods: Two hundred and fourteen (N = 214) study participants (Healthy control group (N) = 178; Early AMD group (N) = 36) were enrolled after getting their written informed consent. The MPOD of the study participants was assessed using MPS II (Electron Technology, UK) after completing their routine ocular examination. Serum lipids were measured by the standard technique. Plasma levels of L, Z, lycopene and beta-carotene were estimated by high performance liquid chromatography with photo diode array detector. Statistical analysis used: Correlations among variables in serum, plasma and the MPOD were established using Spearman's rho correlation coefficient. Results: The overall mean MPOD in healthy control group and early AMD group were found to be 0.47 ± 0.16 (N = 178; 317 eyes) and 0.35 ± 0.22 (N = 36; 38 eyes) at 1° eccentricity respectively and were found to be statistically significant (p < 0.001). A strong positive association was found between plasma L, Z and L + Z and MPOD. Serum HDL showed a strong negative association with MPOD and other lipids showed a very weak association. MPOD was unaffected by body mass index. Conclusions: MPOD is positively associated with plasma L,Z and L + Z, adding further evidence that additional intake of L/Z may be beneficial in delaying the risk of AMD in our population.},
}
@article {pmid39160663,
year = {2024},
author = {Moon, JY and Kim, HJ and Cho, SC},
title = {Two-year Outcomes of Intravitreal Aflibercept Injection for Neovascular Age-related Macular Degeneration with "Observe before Treat-and-Extend" Method.},
journal = {Korean journal of ophthalmology : KJO},
volume = {38},
number = {5},
pages = {380-391},
pmid = {39160663},
issn = {2092-9382},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; Aged ; Follow-Up Studies ; *Tomography, Optical Coherence/methods ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Time Factors ; Aged, 80 and over ; Fluorescein Angiography/methods ; Macula Lutea/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; Fundus Oculi ; },
abstract = {PURPOSE: To evaluate 2-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with "observe before treat-and-extend (O-TAE)" strategy in the real-world setting.<br><br>METHODS: This retrospective study included treatment-naive nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after three monthly loading injections. In case of recurrence, treatment was resumed using the TAE regimen starting from the fourth injection. In case of nonrecurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following three loadings were analyzed.<br><br>RESULTS: A total of 38 eyes of 34 patients were included. Follow-up period was 37.0 &#xb1; 11.0 months. BCVA by logarithm of minimal angle of resolution improved from 0.33 &#xb1; 0.29 at baseline to 0.24 &#xb1; 0.23 in the first year (p = 0.010) and 0.25 &#xb1; 0.22 in the second year (p = 0.054). CMT decreased significantly from 357.43 &#xb1; 74.53 &#x3bc;m at baseline to 269.62 &#xb1; 48.12 &#x3bc;m in the first year (p < 0.001) and 279.14 &#xb1; 54.64 &#x3bc;m in the second year (p < 0.001). Number of injections were 5.11 &#xb1; 1.69 in the first year and 3.84 &#xb1; 2.39 in the second year. The percentage of eyes with a TAE interval of &#x2265;12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after three loadings, 28 eyes (77.8%) recurred, and the average period of recurrence was 6.5 months. The remaining eight eyes (22.2%) had no recurrence during the mean follow-up period of 29.7 months.<br><br>CONCLUSIONS: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.},
}
@article {pmid39156786,
year = {2024},
author = {Wang, XL and Gao, YX and Yuan, QZ and Zhang, M},
title = {NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration: potential therapeutic implications.},
journal = {International journal of ophthalmology},
volume = {17},
number = {8},
pages = {1531-1544},
pmid = {39156786},
issn = {2222-3959},
abstract = {Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells (RGCs). Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasomes, which may affect RGCs in retinal degenerative diseases. The NLRP3 inflammasome was a protein complex that, upon activation, produces caspase-1, mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases. Upregulated autophagy could inhibit NLRP3 inflammasome activation, while inhibited autophagy can promote NLRP3 inflammasome activation, which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina. The activated NLRP3 inflammasome could further inhibit autophagy, thus forming a vicious cycle that accelerated the damage and death of RGCs. This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration, providing a new perspective and direction for the treatment of retinal diseases.},
}
@article {pmid39156554,
year = {2024},
author = {Bikbov, MM and Kazakbaeva, GM and Panda-Jonas, S and Lakupova, EM and Fakhretdinova, AA and Tuliakova, AM and Jonas, JB},
title = {Prevalence and Associated Factors of Cataract, Cataract Surgery and Postoperative Outcome in an Old Population in Russia: The Ural Very Old Study.},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100545},
pmid = {39156554},
issn = {2666-9145},
abstract = {PURPOSE: To assess prevalence of cataract and cataract surgery in a very old population in Russia.<br><br>DESIGN: Population-based study.<br><br>PARTICIPANTS: The Ural Very Old Study included 1526 (81.1%) participants of 1882 eligible individuals aged >85 years.<br><br>METHODS: Series of ophthalmological examinations.<br><br>MAIN OUTCOME MEASURES: Prevalence of cataract and cataract surgery.<br><br>RESULTS: The study included 1163 (76.3%) individuals with lens information. Cataract surgery had been performed in 469 right eyes (41.0%; 95% confidence interval [CI]: 38.1-43.9) (92.1% with posterior chamber intraocular lens [IOL]; 4.7% with multifocal IOL) and 479 left eyes (41.6%; 95% CI: 38.7-44.4) (92.7% with posterior chamber IOL; 4.2% with multifocal IOL). Cataract surgery had been performed in at least one eye for 610 (52.5%) individuals. Higher prevalence of previous cataract surgery correlated (multivariable analysis) with lower IOP (OR: 0.92; 95% CI: 0.88-0.95), glaucomatous optic nerve damage stage (OR: 1.20; 95% CI: 1.05-1.36), and better visual acuity (OR: 0.67; 95% CI: 0.51-0.89). Postoperative best corrected visual acuity was reduced to moderate-to-severe vision impairment (MSVI) in 202 eyes (44.6%; 95% CI: 40.0-49.2) and to blindness in 53 eyes (11.7%; 95% CI: 8.7-14.7). Causes of postoperative MSVI were age-related macular degeneration (AMD) (34.2%), glaucoma (13.9%), and secondary cataract (5.4%). Causes for blindness were AMD (24.5%), glaucoma (18.9%), corneal opacifications (15.8%) and myopic macular degeneration (11.3%). Yttrium Aluminum Garnet-laser capsulotomy had been performed in 6 (1.3%) of 469 right eyes and 12 (2.5%) of 479 left eyes. Prevalence of nuclear cataract and cortical cataract was 604/671 (90.0% in phakic eyes; 51.9% in the whole study population) and 97.9% eyes (48.4% in total study population). Cataract caused bilateral MSVI and blindness in 28.2% (95% CI: 25.6-30) and 2.9% (95% CI: 1.9-3.9), respectively, of all study participants.<br><br>CONCLUSIONS: Despite a relatively high prevalence of cataract surgery, this multiethnic cohort >85 years of aged from Russia showed a high prevalence of cataract-related MSVI and blindness. Main causes for postoperative MSVI (prevalence: 44.6%) and blindness (prevalence: 11.7%) were AMD, glaucoma, corneal opacifications, and myopic macular degeneration. Almost all individuals aged 85+ years need cataract surgery, despite limited chance of postoperative good vision.<br><br>FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid39155542,
year = {2025},
author = {Garzone, D and Imtiaz, MA and Mauschitz, MM and Aziz, NA and Holz, FG and Breteler, MMB and Finger, RP},
title = {Age-Related Macular Degeneration and Its Genetic Risk: A Population-based Study.},
journal = {Current eye research},
volume = {50},
number = {1},
pages = {82-86},
doi = {10.1080/02713683.2024.2388692},
pmid = {39155542},
issn = {1460-2202},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; *Macular Degeneration/genetics/epidemiology ; Aged ; *Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Risk Factors ; Germany/epidemiology ; Complement Factor H/genetics ; Polymorphism, Single Nucleotide ; Retinal Drusen/genetics/epidemiology ; Proteins/genetics ; Population Surveillance ; Disease Progression ; },
abstract = {PURPOSE: Specific genetic factors might serve as markers for risk stratification of AMD progression, but their association with key features of AMD has not been fully elucidated. Thus, we investigated the association between overall and pathway-specific genetic risk scores (GRS) and lead loci (ARMS2, CFH) with AMD stages and features of high-risk nonlate AMD, including reticular pseudodrusen (RPD) and large drusen area (LDA).<br><br>METHODS: We performed a cross-sectional analysis of data from the Rhineland Study, a population-based study in Bonn, Germany. We included 4016 individuals aged 50&#x2009;years and older of European descent. GRS and pathway-specific subscores were constructed based on a large genome-wide association study of AMD. Subscores were generated based on gene-pathways associations (complement, extracellular matrix remodeling (ECM) and lipid metabolism). Associations were assessed using logistic and multinomial regression.<br><br>RESULTS: The mean age of participants was 63.36&#x2009;years and 1813 (45.1%) were men. The GRS was positive in 48.1% of individuals and increased, but did not fully overlap, across AMD stages. Pathway-specific subscores increased across AMD stages except for the ECM subscore, which only showed a trend for increasing in late AMD. Increasing overall GRS was associated with RPD and LDA (OR [95%CI] for RPD: 1.70 [1.33-2.15], for LDA: 1.64 [1.29-2.07]) among individuals with AMD. Similarly, higher complement and ECM subscores was associated with RPD, while for LDA, only an association with complement subscore was observed.<br><br>CONCLUSIONS: In a population-based setting, we confirmed higher genetic risk to be associated with more severe AMD and identified associations with high-risk features of intermediate AMD. Conjoint analyses suggested that high-risk features and late AMD might be differentially associated with genetic architecture in AMD, such as ECM remodeling. Incorporation of genetic information such as GRSs might improve AMD risk prediction strategies.},
}
@article {pmid39154860,
year = {2025},
author = {Eichenbaum, DA and Freeman, WR and Chang, MA and Brooks, L and Chaudhry, N and Dadgostar, H and McCannel, CA and Michels, M and Mittra, RA and Wolfe, JD and Beindl, VC and Jaycock, P and Bobbala, A and Gune, S and Spicer, G and Callaway, N},
title = {Endophthalmitis in Eyes Treated with the Port Delivery System with Ranibizumab: Summary of Cases during Clinical Trial Development.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {2},
pages = {127-143},
doi = {10.1016/j.oret.2024.08.005},
pmid = {39154860},
issn = {2468-6530},
mesh = {Humans ; *Endophthalmitis/epidemiology/diagnosis/chemically induced/drug therapy/etiology ; *Ranibizumab/administration &amp; dosage/adverse effects ; Retrospective Studies ; Intravitreal Injections/adverse effects ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Male ; Female ; *Eye Infections, Bacterial/epidemiology/diagnosis/drug therapy/etiology ; Aged ; *Drug Delivery Systems ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Aged, 80 and over ; Middle Aged ; Incidence ; },
abstract = {PURPOSE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration. The United States Prescribing Information has a Boxed Warning for endophthalmitis and reports the incidence rate in patients developing endophthalmitis after receiving the PDS compared with monthly intravitreal ranibizumab. Endophthalmitis cases noted in the Boxed Warning, treatment outcomes, potential contributing factors, and potential mitigations are summarized.<br><br>DESIGN: Retrospective review of endophthalmitis cases in PDS-treated patients in the phase II Ladder (NCT02510794) and phase III Archway (NCT03677934) and Portal (NCT03683251) trials.<br><br>PARTICIPANTS: Endophthalmitis cases in the pooled all-PDS safety population (N&#xa0;= 555) including PDS patients in Ladder, Archway, or Portal.<br><br>METHODS: Ladder patients received PDS (10, 40, or 100 mg/ml) with pro re nata refill-exchanges. Archway patients received PDS 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W). Portal patients received PDS Q24W from day&#xa0;1.<br><br>MAIN OUTCOME MEASURES: Clinical features, management, and visual outcomes were summarized. Cases were summarized by date of PDS implant and/or refill, other prior invasive procedures/refills, and preceding/concurrent conjunctival complications.<br><br>RESULTS: Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021. All were cultured (3 were culture positive) and treated with intravitreal antibiotics. Two cases (2/555 [0.4%]) occurred in the immediate postoperative period (days 5 and 6). Nine cases occurred later (day range: 57-853), including 4 before the first refill-exchange (day range: 57-161). Five patients received between 1 and 11 refill-exchanges before the event (onset: 6-168 days after last refill-exchange). Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or &#x2265;20/40; 4 patients experienced vision loss of &#x2265;15 ETDRS letters.<br><br>CONCLUSIONS: Endophthalmitis is a serious complication that can endanger vision after any ocular procedure, including PDS implantation. Most, but not all, of this limited series of endophthalmitis cases were late onset, associated with conjunctival breach, and recovered vision with treatment. Meticulous attention to PDS surgical techniques with vigilant monitoring of conjunctiva during follow-up may minimize risk of endophthalmitis. Prompt treatment is critical for optimizing patient outcomes.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39154819,
year = {2024},
author = {Tan, B and Chua, J and Wong, D and Liu, X and Ismail, M and Schmetterer, L},
title = {Techniques for imaging the choroid and choroidal blood flow in vivo.},
journal = {Experimental eye research},
volume = {247},
number = {},
pages = {110045},
doi = {10.1016/j.exer.2024.110045},
pmid = {39154819},
issn = {1096-0007},
mesh = {*Choroid/blood supply/diagnostic imaging ; Humans ; *Regional Blood Flow/physiology ; *Tomography, Optical Coherence/methods ; Blood Flow Velocity/physiology ; Laser-Doppler Flowmetry/methods ; Fluorescein Angiography/methods ; Microcirculation/physiology ; Diagnostic Techniques, Ophthalmological ; },
abstract = {The choroid, which is a highly vascularized layer between the retina and sclera, is essential for supplying oxygen and nutrients to the outer retina. Choroidal vascular dysfunction has been implicated in numerous ocular diseases, including age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, and myopia. Traditionally, the in vivo assessment of choroidal blood flow relies on techniques such as laser Doppler flowmetry, laser speckle flowgraphy, pneumotonometry, laser interferometry, and ultrasonic color Doppler imaging. While the aforementioned methods have provided valuable insights into choroidal blood flow regulation, their clinical applications have been limited. Recent advancements in optical coherence tomography and optical coherence tomography angiography have expanded our understanding of the choroid, allowing detailed visualization of the larger choroidal vessels and choriocapillaris, respectively. This review provides an overview of the available techniques that can investigate the choroid and its blood flow in vivo. Future research should combine these techniques to comprehensively image the entire choroidal microcirculation and develop robust methods to quantify choroidal blood flow. The potential findings will provide a better picture of choroidal hemodynamics and its effect on ocular health and disease.},
}
@article {pmid39154616,
year = {2024},
author = {Holland, R and Leingang, O and Bogunović, H and Riedl, S and Fritsche, L and Prevost, T and Scholl, HPN and Schmidt-Erfurth, U and Sivaprasad, S and Lotery, AJ and Rueckert, D and Menten, MJ and , },
title = {Metadata-enhanced contrastive learning from retinal optical coherence tomography images.},
journal = {Medical image analysis},
volume = {97},
number = {},
pages = {103296},
doi = {10.1016/j.media.2024.103296},
pmid = {39154616},
issn = {1361-8423},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Metadata ; *Deep Learning ; Macular Degeneration/diagnostic imaging ; Image Interpretation, Computer-Assisted/methods ; Retina/diagnostic imaging ; },
abstract = {Deep learning has potential to automate screening, monitoring and grading of disease in medical images. Pretraining with contrastive learning enables models to extract robust and generalisable features from natural image datasets, facilitating label-efficient downstream image analysis. However, the direct application of conventional contrastive methods to medical datasets introduces two domain-specific issues. Firstly, several image transformations which have been shown to be crucial for effective contrastive learning do not translate from the natural image to the medical image domain. Secondly, the assumption made by conventional methods, that any two images are dissimilar, is systematically misleading in medical datasets depicting the same anatomy and disease. This is exacerbated in longitudinal image datasets that repeatedly image the same patient cohort to monitor their disease progression over time. In this paper we tackle these issues by extending conventional contrastive frameworks with a novel metadata-enhanced strategy. Our approach employs widely available patient metadata to approximate the true set of inter-image contrastive relationships. To this end we employ records for patient identity, eye position (i.e. left or right) and time series information. In experiments using two large longitudinal datasets containing 170,427 retinal optical coherence tomography (OCT) images of 7912 patients with age-related macular degeneration (AMD), we evaluate the utility of using metadata to incorporate the temporal dynamics of disease progression into pretraining. Our metadata-enhanced approach outperforms both standard contrastive methods and a retinal image foundation model in five out of six image-level downstream tasks related to AMD. We find benefits in both a low-data and high-data regime across tasks ranging from AMD stage and type classification to prediction of visual acuity. Due to its modularity, our method can be quickly and cost-effectively tested to establish the potential benefits of including available metadata in contrastive pretraining.},
}
@article {pmid39152209,
year = {2024},
author = {Holste, G and Lin, M and Zhou, R and Wang, F and Liu, L and Yan, Q and Van Tassel, SH and Kovacs, K and Chew, EY and Lu, Z and Wang, Z and Peng, Y},
title = {Harnessing the power of longitudinal medical imaging for eye disease prognosis using Transformer-based sequence modeling.},
journal = {NPJ digital medicine},
volume = {7},
number = {1},
pages = {216},
pmid = {39152209},
issn = {2398-6352},
support = {R21 EY035296/EY/NEI NIH HHS/United States ; U10 EY009307/EY/NEI NIH HHS/United States ; U10 EY009341/EY/NEI NIH HHS/United States ; R21EY035296//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; },
abstract = {Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classification approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing a disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA significantly outperformed a single-image baseline in 19/20 head-to-head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most influential, prior imaging still provides additional prognostic value.},
}
@article {pmid39151777,
year = {2024},
author = {Wu, S and Zheng, F and Sui, A and Wu, D and Chen, Z},
title = {Sodium-iodate injection can replicate retinal and choroid degeneration in pigmented mice: Using multimodal imaging and label-free quantitative proteomics analysis.},
journal = {Experimental eye research},
volume = {247},
number = {},
pages = {110050},
doi = {10.1016/j.exer.2024.110050},
pmid = {39151777},
issn = {1096-0007},
mesh = {Animals ; *Iodates/toxicity ; *Proteomics/methods ; Mice ; *Tomography, Optical Coherence/methods ; *Multimodal Imaging ; *Retinal Pigment Epithelium/metabolism/pathology/diagnostic imaging ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Fluorescein Angiography/methods ; *Choroid/metabolism/pathology ; Retinal Degeneration/metabolism/diagnostic imaging/pathology/chemically induced ; Oxidative Stress ; Microscopy, Electron, Transmission ; Eye Proteins/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO3), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO3-treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO3 injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO3-treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood.},
}
@article {pmid39151775,
year = {2024},
author = {Ogata, T and Ashimori, A and Higashijima, F and Sakuma, A and Hamada, W and Sunada, J and Aoki, R and Mikuni, M and Hayashi, K and Yoshimoto, T and Wakuta, M and Teranishi, S and Ohta, M and Kimura, K},
title = {HIF-1α-dependent regulation of angiogenic factor expression in Müller cells by mechanical stimulation.},
journal = {Experimental eye research},
volume = {247},
number = {},
pages = {110051},
doi = {10.1016/j.exer.2024.110051},
pmid = {39151775},
issn = {1096-0007},
mesh = {Humans ; *Ependymoglial Cells/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; Cells, Cultured ; *Stress, Mechanical ; *Gene Expression Regulation ; Enzyme-Linked Immunosorbent Assay ; RNA, Messenger/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Angiopoietin-1/metabolism/genetics ; Blotting, Western ; },
abstract = {Mechanical stress regulates various biological processes in cells, tissues, and organs as well as contributes to the pathogenesis of various diseases. The retina is subjected to mechanical stress imposed by intraocular pressure as well as by retinal hemorrhage and edema. Responses to mechanical stress have been studied in retinal pigment epithelial cells and Müller cells of the retina, with the former cells having been found to undergo a stress-induced increase in the expression of vascular endothelial growth factor (VEGF), which plays a key role in physiological and pathological angiogenesis in the retina. We here examined the effects of stretch stimulation on the expression of angiogenic factors in cultured human Müller cells. Reverse transcription and quantitative PCR analysis revealed that expression of the VEGF-A gene was increased by such stimulation in Müller cells, whereas that of the angiopoietin 1 gene was decreased. An enzyme-linked immunosorbent assay showed that stretch stimulation also increased VEGF secretion from these cells. Expression of the transcription factor HIF-1α (hypoxia-inducible factor-1α) was increased at both mRNA and protein levels by stretch stimulation, and the HIF-1α inhibitor CAY10585 prevented the effects of mechanical stress on VEGF-A gene expression and VEGF secretion. Furthermore, RNA-sequencing analysis showed that the expression of angiogenesis-related pathway genes was upregulated by stretch stimulation. Our results thus suggest that mechanical stress induces VEGF production in Müller cells in a manner dependent on HIF-1α, and that HIF-1α is therefore a potential therapeutic target for conditions such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion.},
}
@article {pmid39151755,
year = {2025},
author = {Schmidt-Erfurth, U and Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Scheibler, L and Bogunovic, H},
title = {Disease Activity and Therapeutic Response to Pegcetacoplan for Geographic Atrophy Identified by Deep Learning-Based Analysis of OCT.},
journal = {Ophthalmology},
volume = {132},
number = {2},
pages = {181-193},
doi = {10.1016/j.ophtha.2024.08.017},
pmid = {39151755},
issn = {1549-4713},
mesh = {Humans ; *Geographic Atrophy/drug therapy/diagnosis ; *Deep Learning ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology ; Aged ; Male ; Female ; Prospective Studies ; Visual Acuity/physiology ; Aged, 80 and over ; Photoreceptor Cells, Vertebrate/pathology ; Middle Aged ; Fluorescein Angiography ; Follow-Up Studies ; },
abstract = {PURPOSE: To quantify morphological changes of the photoreceptors (PRs) and retinal pigment epithelium (RPE) layers under pegcetacoplan therapy in geographic atrophy (GA) using deep learning-based analysis of OCT images.<br><br>DESIGN: Post hoc longitudinal image analysis.<br><br>PARTICIPANTS: Patients with GA due to age-related macular degeneration from 2 prospective randomized phase III clinical trials (OAKS and DERBY).<br><br>METHODS: Deep learning-based segmentation of RPE loss and PR degeneration, defined as loss of the ellipsoid zone (EZ) layer on OCT, over 24 months.<br><br>MAIN OUTCOME MEASURES: Change in the mean area of RPE loss and EZ loss over time in the pooled sham arms and the pegcetacoplan monthly (PM)/pegcetacoplan every other month (PEOM) treatment arms.<br><br>RESULTS: A total of 897 eyes of 897 patients were included. There was a therapeutic reduction of RPE loss growth by 22% and 20% in OAKS and 27% and 21% in DERBY for PM and PEOM compared with sham, respectively, at 24 months. The reduction on the EZ level was significantly higher with 53% and 46% in OAKS and 47% and 46% in DERBY for PM and PEOM compared with sham at 24 months. The baseline EZ-RPE difference had an impact on disease activity and therapeutic response. The therapeutic benefit for RPE loss increased with larger EZ-RPE difference quartiles from 21.9%, 23.1%, and 23.9% to 33.6% for PM versus sham (all P < 0.01) and from 13.6% (P&#xa0;= 0.11), 23.8%, and 23.8% to 20.0% for PEOM versus sham (P < 0.01) in quartiles 1, 2, 3, and 4, respectively, at 24 months. The therapeutic reduction of EZ loss increased from 14.8% (P&#xa0;= 0.09), 33.3%, and 46.6% to 77.8% (P < 0.0001) between PM and sham and from 15.9% (P&#xa0;= 0.08), 33.8%, and 52.0% to 64.9% (P < 0.0001) between PEOM and sham for quartiles 1 to 4 at 24 months.<br><br>CONCLUSIONS: Deep learning-based OCT analysis objectively identifies and quantifies PR and RPE degeneration in GA. Reductions in further EZ loss on OCT are even higher than the effect on RPE loss in phase 3 trials of pegcetacoplan treatment. The EZ-RPE difference has a strong impact on disease progression and therapeutic response. Identification of patients with higher EZ-RPE loss difference may become an important criterion for the management of GA secondary to AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39150604,
year = {2024},
author = {Sivaprasad, S and Chandra, S and Sadda, S and Teo, KYC and Thottarath, S and de Cock, E and Empeslidis, T and Esmaeelpour, M},
title = {Predict and Protect: Evaluating the Double-Layer Sign in Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {10},
pages = {2511-2541},
pmid = {39150604},
issn = {2193-8245},
abstract = {INTRODUCTION: Advanced age-related macular degeneration (AMD) is a major cause of vision loss. Therefore, there is interest in precursor lesions that may predict or prevent the onset of advanced AMD. One such lesion is a shallow separation of the retinal pigment epithelium (RPE) and Bruch's membrane (BM), which is described by various terms, including double-layer sign (DLS).<br><br>METHODS: In this article, we aim to examine and clarify the different terms referring to shallow separation of the RPE and BM. We also review current evidence on the outcomes associated with DLS: firstly, whether DLS is predictive of exudative neovascular AMD; and secondly, whether DLS has potential protective properties against geographic atrophy.<br><br>RESULTS: The range of terms used to describe a shallow separation of the RPE and BM reflects that DLS can present with different characteristics. While vascularised DLS appears to protect against atrophy but can progress to exudation, non-vascularised DLS is associated with an increased risk of atrophy. Optical coherence tomography (OCT) angiography (OCTA) is the principal method for identifying and differentiating various forms of DLS. If OCTA is unavailable or not practically possible, simplified classification of DLS as thick or thin, using OCT, enables the likelihood of vascularisation to be approximated. Research is ongoing to automate DLS detection by applying deep-learning algorithms to OCT scans.<br><br>CONCLUSIONS: The term DLS remains applicable for describing shallow separation of the RPE and BM. Detection and classification of this feature provides valuable information regarding the risk of progression to advanced AMD. However, the appearance of DLS and its value in predicting AMD progression can vary between patients. With further research, individualised risks can be confirmed to inform appropriate treatment.},
}
@article {pmid39149709,
year = {2024},
author = {Rizzo, S and Savastano, MC and Falsini, B and Bernardinelli, P and Boselli, F and De Vico, U and Carlà, MM and Giannuzzi, F and Fossataro, C and Gambini, G and Crincoli, E and Ferrara, S and Ripa, M and Killian, R and Rizzo, C and Valentini, CG and Orlando, N and Placidi, G and Teofili, L and Savastano, A},
title = {Safety Results for Geographic Atrophy Associated with Age-Related Macular Degeneration Using Subretinal Cord Blood Platelet-Rich Plasma.},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100476},
pmid = {39149709},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD).<br><br>DESIGN: Interventional, open-label study started in January 2021 with follow-up at 12 months (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov NCT04636853).<br><br>PARTICIPANTS: Thirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months.<br><br>INTERVENTION: All 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-gauge needle.<br><br>MAIN OUTCOMES AND MEASURES: Best-corrected visual acuity (BCVA) with ETDRS letters, central macular thickness using OCT, and atrophic area measured on en face OCT images were assessed at baseline, 1, 3, 6, and 12 months.<br><br>RESULTS: The BCVA in the treated group was 34.46 &#xb1; 20.8 ETDRS at baseline, 40.84 &#xb1; 20.52 at 1 month, 40.07 &#xb1; 20.34 at 3 months, 39.38 &#xb1; 19.84 at 6 months, and 35.84 &#xb1; 18.38 at 12 months. In the untreated group, the BCVA was 53 &#xb1; 21.1 ETDRS letters at baseline, 51.54 &#xb1; 20.99 at 1 month, 46.62 &#xb1; 19.47 at 3 months, 46.85 &#xb1; 18.58 at 6 months, and 43.92 &#xb1; 17.97 at 12 months (2-way analysis of variance: interaction of treatment by eye or time, P&#xa0;= 0.084). Central macular thickness did not show a significant intereye difference at 12 months (P&#xa0;= 0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months (P < 0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up.<br><br>CONCLUSIONS: Subretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed to understand whether the CB-PRP could have a role in the GA treatment.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39149621,
year = {2024},
author = {Savastano, A and D'Onofrio, NC and Francione, G and Sasso, P and Hu, L and Rizzo, S},
title = {SING IMT in pseudophakic eyes: Results of the first experiences.},
journal = {American journal of ophthalmology case reports},
volume = {36},
number = {},
pages = {102119},
pmid = {39149621},
issn = {2451-9936},
abstract = {PURPOSE: To evaluate the feasibility and outcomes of implanting the Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT) in pseudophakic patients affected by late-stage dry AMD.<br><br>SUBJECTS: Five pseudophakic patients' eyes with stable dry AMD were suitable for SING IMT implantation. Four eyes were excluded because of previous YAG laser capsulotomy. Patients underwent preoperative assessments, including visual acuity measurements and OCT scans.<br><br>METHODS: Surgical procedures were performed under peribulbar anesthesia, with careful IOL removal and SING IMT implantation. Postoperative follow-up was conducted at regular intervals to monitor visual acuity, device positioning and complications.<br><br>RESULTS: Postoperative outcomes demonstrated improvements in visual acuity for most patients with an average gain in CDVA (Corrected Distance Visual Acuity) and CNVA (Corrected Near Visual Acuity) of 16,8&#xa0;&#xb1;&#xa0;10,2 and 13,8&#xa0;&#xb1;&#xa0;7,4 ETDRS letters, respectively. Limited complications have been observed. In one case, we observed dislocation of the device into the vitreous chamber, which we managed through vitrectomy and scleral fixation of the SING IMT using GoreTex suture.<br><br>CONCLUSIONS: Despite being traditionally contraindicated for pseudophakic patients, SING IMT implantation in selected cases yielded favorable outcomes, indicating potential benefits for this population. Further research with larger sample sizes and longer follow-up periods is warranted to refine patient selection criteria and optimize surgical techniques.},
}
@article {pmid39149619,
year = {2024},
author = {Ando, T and Kubota, M and Yasukawa, T and Miyase, T and Ishiguro, K and Esaki, Y and Kato, A and Kokuzawa, S and Hirano, Y and Sakaguchi, H},
title = {Macular hole with retinal pigment epithelium tear after anti-VEGF therapy in an eye with neovascular age-related macular degeneration.},
journal = {American journal of ophthalmology case reports},
volume = {36},
number = {},
pages = {102126},
pmid = {39149619},
issn = {2451-9936},
abstract = {PURPOSE: To report a case of a full-thickness macular hole (FTMH) associated with a retinal pigment epithelium (RPE) tear after anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nvAMD), which was successfully closed by vitreous surgery.<br><br>OBSERVATIONS: A 73-year-old man with nvAMD in the right eye received an intravitreal aflibercept injection due to enlarged pigment epithelial detachment. However, 2 days after the third injection, the patient experienced a sudden decline in vision. An FTMH with a tear in the underlying RPE was detected. The FTMH was closed using vitrectomy combined with the inverted internal limiting membrane (ILM) flap technique.<br><br>CONCLUSIONS AND IMPORTANCE: Our case highlights a rare complication of both an FTMH and an RPE tear after anti-VEGF therapy. Vitrectomy, with the inverted ILM flap technique, proved effective in closing the FTMH despite the complexity of the case.},
}
@article {pmid39149137,
year = {2024},
author = {Luo, Y and Liu, J and Feng, W and Lin, D and Chen, M and Zheng, H},
title = {Single-cell RNA Sequencing Identifies Natural Kill Cell-Related Transcription Factors Associated With Age-Related Macular Degeneration.},
journal = {Evolutionary bioinformatics online},
volume = {20},
number = {},
pages = {11769343241272413},
pmid = {39149137},
issn = {1176-9343},
abstract = {BACKGROUND: Age-related Macular Degeneration (AMD) poses a growing global health concern as the leading cause of central vision loss in elderly people.<br><br>OBJECTION: This study focuses on unraveling the intricate involvement of Natural Killer (NK) cells in AMD, shedding light on their immune responses and cytokine regulatory roles.<br><br>METHODS: Transcriptomic data from the Gene Expression Omnibus database were utilized, employing single-cell RNA-seq analysis. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and single-cell regulatory network inference and clustering (SCENIC) analysis were applied to reveal the regulatory mechanisms of NK cells in early-stage AMD patients. Machine learning models, such as random forests and decision trees, were employed to screen hub genes and key transcription factors (TFs) associated with AMD.<br><br>RESULTS: Distinct cell clusters were identified in the present study, especially the T/NK cluster, with a notable increase in NK cell abundance observed in AMD. Cell-cell communication analyses revealed altered interactions, particularly in NK cells, indicating their potential role in AMD pathogenesis. HdWGCNA highlighted the turquoise module, enriched in inflammation-related pathways, as significantly associated with AMD in NK cells. The SCENIC analysis identified key TFs in NK cell regulatory networks. The integration of hub genes and TFs identified CREM, FOXP1, IRF1, NFKB2, and USF2 as potential predictors for AMD through machine learning.<br><br>CONCLUSION: This comprehensive approach enhances our understanding of NK cell dynamics, signaling alterations, and potential predictive models for AMD. The identified TFs provide new avenues for molecular interventions and highlight the intricate relationship between NK cells and AMD pathogenesis. Overall, this study contributes valuable insights for advancing our understanding and management of AMD.},
}
@article {pmid39148570,
year = {2024},
author = {Perez, AM and Chau, VQ and Sridhar, J},
title = {Medical Accuracy of Reddit in Patient Discussions of Prospective Ocular Stem Cell Therapies for Retinal Degenerative Diseases.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {4},
pages = {410-414},
pmid = {39148570},
issn = {2474-1272},
abstract = {Purpose: To evaluate the medical accuracy in discussions of stem cell therapy for retinal diseases on a social media internet forum (Reddit). Methods: A cross-sectional study assessed 11 Reddit forums and 411 unique comments from 2017 to 2022. Evaluated participants were all anonymous Reddit users. Discussions were independently examined for medical accuracy by a board-certified, fellowship-trained retina surgeon in active practice. Results: Reddit users self-identified mainly as prospective patients followed by research students and physicians or healthcare workers. Inquiries mostly regarded stem cell treatment for macular degeneration. Thirty-six percent of the forum's content was found to be inaccurate or misleading. When specifically considering factual comments, the inaccuracy rate increased to 54%. Identified gaps in knowledge mostly regarded the current state of the technology (25%) followed by misinterpretation of trial results (16%) and scam treatments (14%). Most inaccurate or misleading comments favored stem cell advancements (72%). Conclusions: This study highlights the gaps in knowledge and areas of medical misinformation regarding ocular stem cell therapies shared by individuals on Reddit.},
}
@article {pmid39148568,
year = {2024},
author = {Cohen, SA and Brant, A and Rayess, N and Rahimy, E and Pan, C and Fisher, AC and Pershing, S and Do, D},
title = {Google Trends-Assisted Analysis of the Readability, Accountability, and Accessibility of Online Patient Education Materials for the Treatment of AMD After US FDA Approval of Pegcetacoplan.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {4},
pages = {421-427},
pmid = {39148568},
issn = {2474-1272},
abstract = {Purpose: To evaluate the readability, accountability, accessibility, and source of online patient education materials for treatment of age-related macular degeneration (AMD) and to quantify public interest in Syfovre and geographic atrophy after US Food and Drug Administration (FDA) approval. Methods: Websites were classified into 4 categories by information source. Readability was assessed using 5 validated readability indices. Accountability was assessed using 4 benchmarks of the Journal of the American Medical Association (JAMA). Accessibility was evaluated using 3 established criteria. The Google Trends tool was used to evaluate temporal trends in public interest in "Syfovre" and "geographic atrophy" in the months after FDA approval. Results: Of 100 websites analyzed, 22% were written below the recommended sixth-grade reading level. The mean (±SD) grade level of analyzed articles was 9.76 ± 3.35. Websites averaged 1.40 ± 1.39 (of 4) JAMA accountability metrics. The majority of articles (67%) were from private practice/independent organizations. A significant increase in the public interest in the terms "Syfovre" and "geographic atrophy" after FDA approval was found with the Google Trends tool (P < .001). Conclusions: Patient education materials related to AMD treatment are often written at inappropriate reading levels and lack established accountability and accessibility metrics. Articles from national organizations ranked highest on accessibility metrics but were less visible on a Google search, suggesting the need for visibility-enhancing measures. Patient education materials related to the term "Syfovre" had the highest average reading level and low accountability, suggesting the need to modify resources to best address the needs of an increasingly curious public.},
}
@article {pmid39148567,
year = {2024},
author = {Huang, Y and Choo, C and Hancock, S and Ciulla, TA and Wykoff, CC and Shantha, JG and Yeh, S},
title = {Suprachoroidal Drug Delivery for Macular Edema Associated With Noninfectious Uveitis.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {4},
pages = {401-409},
pmid = {39148567},
issn = {2474-1272},
support = {R01 EY029594/EY/NEI NIH HHS/United States ; },
abstract = {Purpose: To evaluate clinical trials in the literature that focus on suprachoroidal drug delivery for the treatment of noninfectious uveitis and other posterior segment diseases. Methods: A synthesis of the literature was performed. Results: In 2021, suprachoroidal space triamcinolone acetonide, a corticosteroid delivery system used for the treatment of uveitic macular edema (ME), was approved by the US Food and Drug Administration. The drug-delivery system targets the suprachoroidal space using a microneedle-based device and has a favorable pharmacokinetic profile. Suprachoroidally administered investigational therapies have also been assessed in clinical trials for other posterior segment diseases, including diabetic ME, retinal vein occlusion, age-related macular degeneration, and choroidal melanoma. Conclusions: The safety and efficacy of suprachoroidal corticosteroid injections to treat uveitic ME have been shown in recent phase III clinical trials. Multiple programs are also investigating this modality of drug delivery for use in many other retinal and choroidal pathologies.},
}
@article {pmid39148556,
year = {2024},
author = {Zhaoping, L},
title = {Looking with or without seeing in an individual with age-related macular degeneration impairing central vision.},
journal = {i-Perception},
volume = {15},
number = {4},
pages = {20416695241265821},
pmid = {39148556},
issn = {2041-6695},
abstract = {Looking leads gaze to objects; seeing recognizes them. Visual crowding makes seeing difficult or impossible before looking brings objects to the fovea. Looking before seeing can be guided by saliency mechanisms in the primary visual cortex (V1). We have proposed that looking and seeing are mainly supported by peripheral and central vision, respectively. This proposal is tested in an observer with central vision loss due to macular degeneration, using a visual search task that can be accomplished solely through looking, but is actually impeded through seeing. The search target is an uniquely oriented, salient, bar among identically shaped bars. Each bar, including the target, is part of an " " X " shape. The target's " X is identical to, although rotated from, the other " X 's in the image, which normally causes confusion. However, this observer exhibits no such confusion, presumably because she cannot see the " X 's shape, but can look towards the target. This result demonstrates a critical dichotomy between central and peripheral vision.},
}
@article {pmid39148091,
year = {2024},
author = {Rassi, TNO and Barbosa, LM and Pereira, S and Novais, EA and Penha, F and Roisman, L and Maia, M},
title = {Photobiomodulation efficacy in age-related macular degeneration: a systematic review and meta-analysis of randomized clinical trials.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {54},
pmid = {39148091},
issn = {2056-9920},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated.<br><br>METHODS: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI).<br><br>RESULTS: We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12&#xa0;mm&#xb3;; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias.<br><br>CONCLUSION: This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM's therapeutic potential for dry AMD.},
}
@article {pmid39147864,
year = {2025},
author = {Tillmann, A and Turgut, F and Munk, MR},
title = {Optical coherence tomography angiography in neovascular age-related macular degeneration: comprehensive review of advancements and future perspective.},
journal = {Eye (London, England)},
volume = {39},
number = {5},
pages = {835-844},
pmid = {39147864},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods/trends ; *Fluorescein Angiography/methods/trends ; *Wet Macular Degeneration/diagnostic imaging/diagnosis ; Artificial Intelligence ; *Retinal Vessels/diagnostic imaging/pathology ; *Choroidal Neovascularization/diagnostic imaging ; },
abstract = {Optical coherence tomography angiography (OCTA) holds promise in enhancing the care of various retinal vascular diseases, including neovascular age-related macular degeneration (nAMD). Given nAMD's vascular nature and the distinct vasculature of macular neovascularization (MNV), detailed analysis is expected to gain significance. Research in artificial intelligence (AI) indicates that en-face OCTA views may offer superior predictive capabilities than spectral domain optical coherence tomography (SD-OCT) images, highlighting the necessity to identify key vascular parameters. Analyzing vasculature could facilitate distinguishing MNV subtypes and refining diagnosis. Future studies correlating OCTA parameters with clinical data might prompt a revised classification system. However, the combined utilization of qualitative and quantitative OCTA biomarkers to enhance the accuracy of diagnosing disease activity remains underdeveloped. Discrepancies persist regarding the optimal biomarker for indicating an active lesion, warranting comprehensive prospective studies for validation. AI holds potential in extracting valuable insights from the vast datasets within OCTA, enabling researchers and clinicians to fully exploit its OCTA imaging capabilities. Nevertheless, challenges pertaining to data quantity and quality pose significant obstacles to AI advancement in this field. As OCTA gains traction in clinical practice and data volume increases, AI-driven analysis is expected to further augment diagnostic capabilities.},
}
@article {pmid39145794,
year = {2025},
author = {Sacconi, R and Beretta, F and Bandello, F and Querques, G},
title = {Geographic Atrophy-associated Intraretinal Neovascularization (GAIN): A novel clinical entity.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {263},
number = {1},
pages = {231-233},
pmid = {39145794},
issn = {1435-702X},
mesh = {Humans ; *Retinal Neovascularization/diagnosis/etiology ; *Geographic Atrophy/diagnosis/complications ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Fundus Oculi ; *Visual Acuity ; },
abstract = {KEY MESSAGES : WHAT IS KNOWN : Geographic atrophy could be associated with MNV or other vascular alterations. Intraretinal fluid could be present in GA also without neovascularization. WHAT IS NEW : GAIN is a novel clinical entity characterized by GA and an intraretinal neovascular network. GAIN could be exudative or non-exudative.},
}
@article {pmid39144648,
year = {2024},
author = {Chantarasorn, Y and Funilkul, K},
title = {A Temporal Association between Regression of Pachydrusen and Use of Proprotein Convertase Subtilisin Kexin 9 Inhibitor: A Case Report.},
journal = {Case reports in ophthalmology},
volume = {15},
number = {1},
pages = {614-620},
pmid = {39144648},
issn = {1663-2699},
abstract = {INTRODUCTION: We aim to report the clinical course of a patient with pachychoroidopathy who experienced regression of subfoveal drusen during cholesterol treatment using PCSK9 inhibitors.<br><br>CASE PRESENTATION: A 62-year-old woman who was visually asymptomatic complained of recent visual loss in the left eye (OS). She was diagnosed with foveal pachydrusen (OS) that had remained stable for 10 years. Three months after starting cholesterol treatment with a PCSK9 inhibitor, the latest class of lipid-lowering medication, her vision improved in parallel with gradual regression of material deposited beneath the retinal pigment epithelium (RPE). Recurrence of drusen was observed after discontinuing the drug.<br><br>CONCLUSIONS: Use of PCSK9 inhibitors may improve the retina's lipid homeostasis by increasing the number of RPE-LDL receptors and partly contribute to the improvement of ocular phenotypes associated with dysfunctional RPE in pachychoroidopathy.},
}
@article {pmid39143611,
year = {2024},
author = {Chen, J and Yuan, XL and Zhou, X and Xu, J and Zhang, X and Duan, X},
title = {Mendelian randomization implicates causal association between epigenetic age acceleration and age-related eye diseases or glaucoma endophenotypes.},
journal = {Clinical epigenetics},
volume = {16},
number = {1},
pages = {106},
pmid = {39143611},
issn = {1868-7083},
support = {2023TP2225//Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in the Diagnosis and Application of New Materials, China/ ; 2023JJ70014//Natural Science Foundation of Hunan Province, China/ ; kq2208495//Changsha Municipal Natural Science Foundation, China/ ; AR2206D5//Science and Technology Foundation of Aier Eye Hospital Group, China/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Epigenesis, Genetic/genetics ; *Genome-Wide Association Study/methods ; *DNA Methylation/genetics ; *Endophenotypes ; Male ; *Aging/genetics ; Female ; Glaucoma/genetics ; Middle Aged ; Glaucoma, Open-Angle/genetics ; Aged ; Genetic Predisposition to Disease ; },
abstract = {BACKGROUND: Age-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes.<br><br>METHODS: Instrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates.<br><br>RESULTS: The results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR&#x2009;=&#x2009;1.04, 95% CI 1.02&#xa0;to&#xa0;1.06, P&#x2009;=&#x2009;6.1E-04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR&#x2009;=&#x2009;0.92, 95% CI 0.86&#xa0;to&#xa0;0.99, P&#x2009;=&#x2009;0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (&#x3b2;&#x2009;=&#x2009;-0.190 year, 95% CI -0.374 to -0.008, P&#x2009;=&#x2009;0.041). The EEA of HannumAge (&#x3b2;&#x2009;=&#x2009;-0.85 &#x3bc;m, 95% CI -1.57 to -0.14, P&#x2009;=&#x2009;0.019) and HorvathAge (&#x3b2;&#x2009;=&#x2009;-0.63 &#x3bc;m, 95% CI -1.18 to -0.08, P&#x2009;=&#x2009;0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (&#x3b2;&#x2009;=&#x2009;0.06 &#x3bc;m, 95% CI 0.01 to 0.11, P&#x2009;=&#x2009;0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P&#x2009;<&#x2009;0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: The present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs.},
}
@article {pmid39143171,
year = {2024},
author = {Naghdi, A and Oska, N and Yumnamcha, T and Eltanani, S and Shawky, M and Me, R and Ibrahim, AS},
title = {The significance of upper glycolytic components in regulating retinal pigment epithelial cellular behavior.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {18862},
pmid = {39143171},
issn = {2045-2322},
support = {R01 EY034964/EY/NEI NIH HHS/United States ; },
mesh = {*Glycolysis/physiology ; *Retinal Pigment Epithelium/metabolism ; *Cell Adhesion ; Extracellular Matrix/metabolism ; *Electric Impedance ; Humans ; Lactate Dehydrogenases/metabolism ; Fructose-Bisphosphate Aldolase/metabolism ; Enzyme Inhibitors/pharmacology ; Cell Line ; Cell Survival ; Phosphofructokinases/metabolism ; },
abstract = {Cell adhesion to the extracellular matrix and its natural outcome of cell spreading, along with the maintenance of barrier activity, are essential behaviors of epithelial cells, including retinal pigment epithelium (RPE). Disruptions in these characteristics can result in severe vision-threatening diseases such as diabetic macular edema and age-related macular degeneration. However, the precise mechanisms underlying how RPE cells regulate their barrier integrity and cell spreading are not fully understood. This study aims to elucidate the relative importance of upper glycolytic components in governing these cellular behaviors of RPE cells. Electric Cell-Substrate Impedance Sensing (ECIS) technology was utilized to assess in real-time the effects of targeting various upper glycolytic enzymes on RPE barrier function and cell spreading by measuring cell resistance and capacitance, respectively. Specific inhibitors used included WZB117 for Glut1 inhibition, Lonidamine for Hexokinase inhibition, PFK158 for PFKFB3/PFK axis inhibition, and TDZD-8 for Aldolase inhibition. Additionally, the viability of RPE cells was evaluated using a lactate dehydrogenase (LDH) cytotoxicity assay. The most significant decrease in electrical resistance and increase in capacitance of RPE cells were observed due to dose-dependent inhibition of Glut1 using WZB117, as well as Aldolase inhibition with TDZD-8. LDH level analysis at 24-72 h post-treatment with WZB117 (1 and 10 μM) or TDZD-8 (1 μM) showed no significant difference compared to the control, indicating that the disruption of RPE functionality was not attributed to cell death. Lastly, inhibition of other upper glycolytic components, including PFKFB3/PFK with PFK158 or Hexokinase with Lonidamine, did not significantly affect RPE cell behavior. This study provides insights into the varied roles of upper glycolytic components in regulating the functionality of RPE cells. Specifically, it highlights the critical roles of Glut1 and Aldolase in preserving barrier integrity and promoting RPE cell adhesion and spreading. Such understanding will guide the development of safe interventions to treat RPE cell dysfunction in various retinal disorders.},
}
@article {pmid39141809,
year = {2024},
author = {Ghosh, TN and Rotake, DR and Singh, SG},
title = {Succinimide-Functionalized Reduced Graphene Oxide Nanosheets: A High-throughput Resistive Sensing Platform for Age-Related Macular Degeneration Biomarker Determination Using Human Tears.},
journal = {ACS applied bio materials},
volume = {7},
number = {9},
pages = {6014-6024},
doi = {10.1021/acsabm.4c00636},
pmid = {39141809},
issn = {2576-6422},
mesh = {*Graphite/chemistry ; Humans ; *Biosensing Techniques ; *Succinimides/chemistry ; *Biomarkers/analysis ; *Macular Degeneration ; *Tears/chemistry ; Materials Testing ; Biocompatible Materials/chemistry ; Particle Size ; Nanostructures/chemistry ; Oxides/chemistry ; },
abstract = {Age-related macular degeneration (AMD) is a well-recognized affliction among the elderly, causing vision impairment ranging from blurred vision to complete blindness. This underscores the critical need for accurate, precise, and early detection methods. Herein, we developed a noninvasive, label-free electrical biosensor, constructed on an economical printed circuit board (PCB) substrate, designed specifically for the precise quantification of AMD biomarker: complement component III (C3). The hydrothermally reduced graphene oxide (rGO) was deposited between gold-interdigitated microelectrodes, forming a conductive channel. The fabricated C3 biosensor exhibits a low detection limit of 0.4342 ng/mL and an impressive sensitivity of 9.238 ((ΔR/R)/ng.mL[-1])/cm[2] with a regression coefficient of 0.9815 calibrated within the clinical C3 range of 10-30 ng/mL. This excellent performance is ascribed to the synergistic effects of 1-pyrenebutanoic acid succinimidyl ester (PBASE) linker and conducting properties of rGO as they generate large active sites for higher anti-C3 antibody immobilization, thereby enhancing sensitivity and specificity. Furthermore, the performance of this proposed C3 sensor chip was validated with enzyme-linked immunosorbent assay (ELISA) using five human tear samples exhibiting an outstanding correlation of a regression value of 0.9774. The unparalleled merits of this newly crafted C3 biosensor transcend those of preceding platforms, boasting superior accuracy and precision in quantifying C3 levels in human tears, accelerated operational speed with results attainable within a mere 15 min, cost-effectiveness, and excellent sensitivity.},
}
@article {pmid39141700,
year = {2024},
author = {Dong, X and Song, Y and Liu, Y and Kou, X and Yang, T and Shi, SX and He, K and Li, Y and Li, Z and Yao, X and Guo, J and Cui, B and Wu, Z and Lei, Y and Du, M and Chen, M and Xu, H and Liu, Q and Shi, FD and Wang, X and Yan, H},
title = {Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice.},
journal = {Science translational medicine},
volume = {16},
number = {760},
pages = {eadi6626},
doi = {10.1126/scitranslmed.adi6626},
pmid = {39141700},
issn = {1946-6242},
mesh = {Animals ; *Killer Cells, Natural/immunology/metabolism ; *Macular Degeneration/pathology ; Humans ; *Extracellular Traps/metabolism ; Choroidal Neovascularization/pathology/metabolism ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Neutrophils/metabolism/immunology ; Male ; Aged ; Female ; },
abstract = {Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.},
}
@article {pmid39141487,
year = {2024},
author = {Lin, TY and Hsieh, YT and Garg, SJ and Chen, LJ and Chen, KJ and Wu, WC and Lai, CC and Hwang, YS and Kang, EY},
title = {Systemic effects of anti-VEGF intravitreal injection in patients with age-related macular degeneration: A multi-institutional real-world study.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 5},
pages = {S809-S815},
pmid = {39141487},
issn = {1998-3689},
mesh = {Humans ; *Intravitreal Injections ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Ranibizumab/administration &amp; dosage/adverse effects ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Bevacizumab/administration &amp; dosage/adverse effects ; *Visual Acuity ; Follow-Up Studies ; Middle Aged ; Macular Degeneration/drug therapy/diagnosis ; Incidence ; Treatment Outcome ; Taiwan/epidemiology ; },
abstract = {PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users.<br><br>METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval.<br><br>RESULTS: This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups.<br><br>CONCLUSION: Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.},
}
@article {pmid39141020,
year = {2024},
author = {Tian, H and Xu, W and Wen, L and Song, T and Tian, Y and Tang, L and Guo, N and Chen, Q and Wang, H and Zhang, K and Zhang, X and Peng, Y},
title = {Relationship between CCL2 gene 2518A/G (rs1024611) polymorphism and age-related macular degeneration susceptibility: meta-analysis and trial sequential analysis.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {348},
pmid = {39141020},
issn = {1573-2630},
mesh = {Humans ; *Chemokine CCL2/genetics ; *Genetic Predisposition to Disease ; *Macular Degeneration/genetics ; *Polymorphism, Single Nucleotide ; },
abstract = {PURPOSE: This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD).<br><br>METHODS: PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed.<br><br>RESULTS: Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings.<br><br>CONCLUSION: The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.},
}
@article {pmid39140961,
year = {2024},
author = {Zhuang, X and Li, M and Mi, L and Zhang, X and Pu, J and He, G and Zhang, L and Yu, H and Yao, L and Chen, H and Ji, Y and Zuo, C and Su, Y and Gan, Y and Hao, X and Zhang, Y and Chen, X and Wen, F},
title = {Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {10},
pages = {24},
pmid = {39140961},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use ; Prospective Studies ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Male ; Female ; Aged ; *Wet Macular Degeneration/drug therapy/metabolism/diagnosis ; *Proteomics ; *Fluorescein Angiography/methods ; *Intravitreal Injections ; *Ranibizumab/therapeutic use ; Aged, 80 and over ; Aqueous Humor/metabolism ; Bevacizumab/therapeutic use ; Metabolomics/methods ; Visual Acuity ; Imaging, Three-Dimensional ; Multiomics ; },
abstract = {PURPOSE: The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements.<br><br>METHODS: In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas.<br><br>RESULTS: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (&#x394;) molecules significantly correlated with at least one type of &#x394;nAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material.<br><br>CONCLUSIONS: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.},
}
@article {pmid39140894,
year = {2025},
author = {Berni, A and Sacconi, R and Zucchiatti, I and Querques, L and Prascina, F and Bandello, F and Querques, G},
title = {Non-exudative choroidal and macular neovascularizations: An overview.},
journal = {European journal of ophthalmology},
volume = {35},
number = {2},
pages = {441-450},
doi = {10.1177/11206721241275206},
pmid = {39140894},
issn = {1724-6016},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnosis ; Fluorescein Angiography/methods ; *Retinal Neovascularization/diagnosis ; *Choroid/blood supply/pathology ; *Macula Lutea/pathology ; Fundus Oculi ; },
abstract = {Non-exudative choroidal and/or macular neovascularizations (NV) represent nowadays a common finding in different retinal disorders. The introduction of non-invasive techniques such as structural optical coherence tomography (OCT) and OCT angiography (OCTA) allowed for easy detection and follow-up of non-exudative NVs. Recognized as a distinct entity, these lesions demonstrate a high variability in terms of pathophysiology, morphology, and prognostic implications. In the absence of a consensus regarding correct classification of subtypes of non-exudative NVs, accurate management through strict follow-up strategies and prompt treatment is required. In this review we offer a comprehensive overview of the non-exudative NV spectrum in various retinal diseases aiming to provide a deeper insight into this clinical entity.},
}
@article {pmid39140090,
year = {2024},
author = {Zucker, CL and Bernstein, PS and Schalek, RL and Lichtman, JW and Dowling, JE},
title = {High-throughput ultrastructural analysis of macular telangiectasia type 2.},
journal = {Frontiers in ophthalmology},
volume = {4},
number = {},
pages = {1428777},
pmid = {39140090},
issn = {2674-0826},
support = {P50 MH094271/MH/NIMH NIH HHS/United States ; U19 NS104653/NS/NINDS NIH HHS/United States ; R01 EY011600/EY/NEI NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; U24 NS109102/NS/NINDS NIH HHS/United States ; R21 EY030255/EY/NEI NIH HHS/United States ; R29 EY011600/EY/NEI NIH HHS/United States ; },
abstract = {INTRODUCTION: Macular Telangiectasia type 2 (MacTel), is an uncommon form of late-onset, slowly-progressive macular degeneration. Associated with regional Müller glial cell loss in the retina and the amino acid serine synthesized by Müller cells, the disease is functionally confined to a central retinal region - the MacTel zone.<br><br>METHODS: We have used high-throughput multi-resolution electron microscopy techniques, optimized for disease analysis, to study the retinas from two women, mother and daughter, aged 79 and 48 years respectively, suffering from MacTel.<br><br>RESULTS: In both eyes, the principal observations made were changes specific to mitochondrial structure both outside and within the MacTel zone in all retinal cell types, with the exception of those in the retinal pigment epithelium (RPE). The lesion areas, which are a hallmark of MacTel, extend from Bruch's membrane and the choriocapillaris, through all depths of the retina, and include cells from the RPE, retinal vascular elements, and extensive hypertrophic basement membrane material. Where the M&#xfc;ller glial cells are lost, we have identified a significant population of microglial cells, exclusively within the Henle fiber layer, which appear to ensheathe the Henle fibers, similar to that seen normally by M&#xfc;ller cells.<br><br>DISCUSSION: Since M&#xfc;ller cells synthesize retinal serine, whereas retinal neurons do not, we propose that serine deficiency, required for normal mitochondrial function, may relate to mitochondrial changes that underlie the development of MacTel. With mitochondrial changes occurring retina-wide, the question remains as to why the M&#xfc;ller cells are uniquely susceptible within the MacTel zone.},
}
@article {pmid39140058,
year = {2024},
author = {Hu, B and Cui, Y and Lee, JJ and Ma, JX and Duerfeldt, AS},
title = {Design and Assessment of First-Generation Heterobifunctional PPARα/STING Modulators.},
journal = {ACS medicinal chemistry letters},
volume = {15},
number = {8},
pages = {1279-1286},
pmid = {39140058},
issn = {1948-5875},
support = {R01 EY030472/EY/NEI NIH HHS/United States ; R01 EY033330/EY/NEI NIH HHS/United States ; R01 EY034510/EY/NEI NIH HHS/United States ; },
abstract = {Inflammatory retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) are prominent causes of blindness in industrialized countries. The complexity of these diseases, involving diverse cell types and pathways that give rise to a multifactorial pathogenesis, complicates drug discovery. As such, therapies exhibiting polypharmacology are expected to improve outcomes through broader disease stage coverage and beneficial spatiotemporal effects. We report herein the first dual modulator of PPARα and STING, two targets tied to disparate pathologies in retinal diseases. Recognizing structural similarities between a reported STING inhibitor SN-013 and our previously described PPARα agonist A229, we designed BH400, which agonizes PPARα (EC50 = 1.2 μM) and inhibits STING (IC50 = 8.1 μM). BH400 demonstrates superior protection over single-target PPARα or STING modulation in microglial and photoreceptor cells. These findings provide compelling evidence for the potential benefit of polypharmacology in common retinal diseases through dual PPARα/STING modulation, motivating further studies.},
}
@article {pmid39139965,
year = {2024},
author = {Zhang, Y and Zhao, X and Liu, Y and Yang, X},
title = {Sulforaphane and ophthalmic diseases.},
journal = {Food science &amp; nutrition},
volume = {12},
number = {8},
pages = {5296-5311},
pmid = {39139965},
issn = {2048-7177},
abstract = {Sulforaphane (SFN) is an organosulfur compound categorized as an isothiocyanate (ITC), primarily extracted from cruciferous vegetables like broccoli and cabbage. The molecular formula of sulforaphane (SFN) is C6H11NOS2. SFN is generated by the hydrolysis of glucoraphanin (GRP) through the enzyme myrosinase, showing notable properties including anti-diabetic, anti-inflammatory, antimicrobial, anti-angiogenic, and anticancer attributes. Ongoing clinical trials are investigating its potential in diseases such as cancer, neurodegenerative diseases, diabetes-related complications, chronic kidney disease, cardiovascular disease, and liver diseases. Several animal carcinogenesis models and cell culture models have shown it to be a very effective chemopreventive agent, and the protective effects of SFN in ophthalmic diseases have been linked to multiple mechanisms. In murine models of diabetic retinopathy and age-related macular degeneration, SFN delays retinal photoreceptor cell degeneration through the Nrf2 antioxidative pathway, NF-κB pathway, AMPK pathway, and Txnip/mTOR pathway. In rabbit models of keratoconus and cataract, SFN has been shown to protect corneal and lens epithelial cells from oxidative stress injury by activating the Keap1-Nrf2-ARE pathway and the Nrf-2/HO-1 antioxidant pathway. Oral delivery or intraperitoneal injection at varying concentrations are the primary strategies for SFN intake in current preclinical studies. Challenges remain in the application of SFN in eye disorders due to its weak solubility in water and limited bioavailability because of the presence of blood-ocular barrier systems. This review comprehensively outlines recent research on SFN, elucidates its mechanisms of action, and discusses potential therapeutic benefits for eye disorders such as age-related macular degeneration (AMD), diabetic retinopathy (DR), cataracts, and other ophthalmic diseases, while also indicating directions for future clinical research to achieve efficient SFN treatment for ophthalmic diseases.},
}
@article {pmid39139633,
year = {2024},
author = {Li, C and Lu, Y and Song, Z and Liu, Y},
title = {A real-world data analysis of ocular adverse events linked to anti-VEGF drugs: a WHO-VigiAccess study.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1398783},
pmid = {39139633},
issn = {1663-9812},
abstract = {INTRODUCTION: Vascular endothelial growth factor (VEGF) is key to wet age-related macular degeneration (wAMD). Anti-VEGF drugs are the main treatment in clinics. This study assessed ocular adverse events (AE) from anti-VEGF drugs in VigiAccess, WHO's database, and compared adverse drug reaction (ADR) profiles of four drugs to aid personalized treatment choices for optimal benefit and safety.<br><br>METHODS: The design was a descriptive retrospective study. We observed four anti-VEGF drugs commonly used in the clinical treatment of wAMD, and their ADR reports came from WHO-VigiAccess. The collected data included the age group, gender, and regional data, as well as the data of disease systems and symptoms caused by ADR recorded in the annual ADR reports and reports received by the WHO. We observed the overall characteristics of the ADR reports of these drugs, then explored the distribution of 27 SOCs of these drugs. Subsequently, we compared the most common ocular ADRs of the drugs. Finally, we compared the commonalities and differences of ocular ADRs related to the drugs.<br><br>RESULTS: Overall, 57,779 AE associated with the four anti-VEGF drugs were reported. The results showed that the number of females experiencing ADRs (67.83%) was significantly higher than males (32.17%), the age group with the highest reported incidence was over 75&#xa0;years old. More than half of the ADR reports came from the Americas (50.86%). The five most common types of AE were: eye disorders (43.56%), general disorders and administration site conditions (34.47%), injury poisoning and procedural complications (13.36%), infections and infestations (11.61%), nervous system disorders (9.99%). Compared with the other three inhibitors, brolucizumab had a significantly higher rate of ocular ADR reports. The most common ocular ADRs of these four anti-VEGF drugs were mostly related to visual impairment, vision blurred, and blindness. However, there is still a disparity of ADRs between different drugs.<br><br>CONCLUSION: The presence of ocular AEs when using anti-VEGF drugs to treat wAMD in clinical practice should attract clinical attention. Clinicians should use these expensive drugs more rationally based on the characteristics of ADRs and develop personalized treatment plans for patients.},
}
@article {pmid39139546,
year = {2024},
author = {Williamson, DJ and Struyven, RR and Antaki, F and Chia, MA and Wagner, SK and Jhingan, M and Wu, Z and Guymer, R and Skene, SS and Tammuz, N and Thomson, B and Chopra, R and Keane, PA},
title = {Artificial Intelligence to Facilitate Clinical Trial Recruitment in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100566},
pmid = {39139546},
issn = {2666-9145},
support = {MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {OBJECTIVE: Recent developments in artificial intelligence (AI) have positioned it to transform several stages of the clinical trial process. In this study, we explore the role of AI in clinical trial recruitment of individuals with geographic atrophy (GA), an advanced stage of age-related macular degeneration, amidst numerous ongoing clinical trials for this condition.<br><br>DESIGN: Cross-sectional study.<br><br>SUBJECTS: Retrospective dataset from the INSIGHT Health Data Research Hub at Moorfields Eye Hospital in London, United Kingdom, including 306&#xa0;651 patients (602&#xa0;826 eyes) with suspected retinal disease who underwent OCT imaging between January 1, 2008 and April&#xa0;10, 2023.<br><br>METHODS: A deep learning model was trained on OCT scans to identify patients potentially eligible for GA trials, using AI-generated segmentations of retinal tissue. This method's efficacy was compared against a traditional keyword-based electronic health record (EHR) search. A clinical validation with fundus autofluorescence (FAF) images was performed to calculate the positive predictive value of this approach, by comparing AI predictions with expert assessments.<br><br>MAIN OUTCOME MEASURES: The primary outcomes included the positive predictive value of AI in identifying trial-eligible patients, and the secondary outcome was the intraclass correlation between GA areas segmented on FAF by experts and AI-segmented OCT scans.<br><br>RESULTS: The AI system shortlisted a larger number of eligible patients with greater precision (1139, positive predictive value: 63%; 95% confidence interval [CI]: 54%-71%) compared with the EHR search (693, positive predictive value: 40%; 95% CI: 39%-42%). A combined AI-EHR approach identified 604 eligible patients with a positive predictive value of 86% (95% CI: 79%-92%). Intraclass correlation of GA area segmented on FAF versus AI-segmented area on OCT was 0.77 (95% CI: 0.68-0.84) for cases meeting trial criteria. The AI also adjusts to the distinct imaging criteria from several clinical trials, generating tailored shortlists ranging from 438 to 1817 patients.<br><br>CONCLUSIONS: This study demonstrates the potential for AI in facilitating automated prescreening for clinical trials in GA, enabling site feasibility assessments, data-driven protocol design, and cost reduction. Once treatments are available, similar AI systems could also be used to identify individuals who may benefit from treatment.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39139544,
year = {2024},
author = {Holland, R and Kaye, R and Hagag, AM and Leingang, O and Taylor, TRP and Bogunović, H and Schmidt-Erfurth, U and Scholl, HPN and Rueckert, D and Lotery, AJ and Sivaprasad, S and Menten, MJ},
title = {Deep Learning-Based Clustering of OCT Images for Biomarker Discovery in Age-Related Macular Degeneration (PINNACLE Study Report 4).},
journal = {Ophthalmology science},
volume = {4},
number = {6},
pages = {100543},
pmid = {39139544},
issn = {2666-9145},
abstract = {PURPOSE: We introduce a deep learning-based biomarker proposal system for the purpose of accelerating biomarker discovery in age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective analysis of a large data set of retinal OCT images.<br><br>PARTICIPANTS: A total of 3456 adults aged between 51 and 102 years whose OCT images were collected under the PINNACLE project.<br><br>METHODS: Our system proposes candidates for novel AMD imaging biomarkers in OCT. It works by first training a neural network using self-supervised contrastive learning to discover, without any clinical annotations, features relating to both known and unknown AMD biomarkers present in 46 496 retinal OCT images. To interpret the learned biomarkers, we partition the images into 30 subsets, termed clusters, that contain similar features. We conduct 2 parallel 1.5-hour semistructured interviews with 2 independent teams of retinal specialists to assign descriptions in clinical language to each cluster. Descriptions of clusters achieving consensus can potentially inform new biomarker candidates.<br><br>MAIN OUTCOME MEASURES: We checked if each cluster showed clear features comprehensible to retinal specialists, if they related to AMD, and how many described established biomarkers used in grading systems as opposed to recently proposed or potentially new biomarkers. We also compared their prognostic value for late-stage wet and dry AMD against an established clinical grading system and a demographic baseline model.<br><br>RESULTS: Overall, both teams independently identified clearly distinct characteristics in 27 of 30 clusters, of which 23 were related to AMD. Seven were recognized as known biomarkers used in established grading systems, and 16 depicted biomarker combinations or subtypes that are either not yet used in grading systems, were only recently proposed, or were unknown. Clusters separated incomplete from complete retinal atrophy, intraretinal from subretinal fluid, and thick from thin choroids, and, in simulation, outperformed clinically used grading systems in prognostic value.<br><br>CONCLUSIONS: Using self-supervised deep learning, we were able to automatically propose AMD biomarkers going beyond the set used in clinically established grading systems. Without any clinical annotations, contrastive learning discovered subtle differences between fine-grained biomarkers. Ultimately, we envision that equipping clinicians with discovery-oriented deep learning tools can accelerate the discovery of novel prognostic biomarkers.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39138426,
year = {2024},
author = {Yadav, DS and Tivig, I and Savopol, T and Moisescu, MG},
title = {Dielectrophoretic characterization of peroxidized retinal pigment epithelial cells as a model of age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {340},
pmid = {39138426},
issn = {1471-2415},
mesh = {*Retinal Pigment Epithelium/pathology/drug effects ; *Macular Degeneration ; Animals ; Rats ; *Hydrogen Peroxide/toxicity/pharmacology ; *Cell Survival ; Electrophoresis/methods ; Oxidative Stress ; Cells, Cultured ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a prevalent ocular pathology affecting mostly the elderly population. AMD is characterized by a progressive retinal pigment epithelial (RPE) cell degeneration, mainly caused by an impaired antioxidative defense. One of the AMD therapeutic procedures involves injecting healthy RPE cells into the subretinal space, necessitating pure, healthy RPE cell suspensions. This study aims to electrically characterize RPE cells to demonstrate a possibility using simulations to separate healthy RPE cells from a mixture of healthy/oxidized cells by dielectrophoresis.<br><br>METHODS: BPEI-1 rat RPE cells were exposed to hydrogen peroxide to create an in-vitro AMD cellular model. Cell viability was evaluated using various methods, including microscopic imaging, impedance-based real-time cell analysis, and the MTS assay. Healthy and oxidized cells were characterized by recording their dielectrophoretic spectra, and electric cell parameters (crossover frequency, membrane conductivity and permittivity, and cytoplasm conductivity) were computed. A COMSOL simulation was performed on a theoretical microfluidic-based dielectrophoretic separation chip using these parameters.<br><br>RESULTS: Increasing the hydrogen peroxide concentration shifted the first crossover frequency toward lower values, and the cell membrane permittivity progressively increased. These changes were attributed to progressive membrane peroxidation, as they were diminished when measured on cells treated with the antioxidant N-acetylcysteine. The changes in the crossover frequency were sufficient for the efficient separation of healthy cells, as demonstrated by simulations.<br><br>CONCLUSIONS: The study demonstrates that dielectrophoresis can be used to separate healthy RPE cells from oxidized ones based on their electrical properties. This method could be a viable approach for obtaining pure, healthy RPE cell suspensions for AMD therapeutic procedures.},
}
@article {pmid39138242,
year = {2024},
author = {Seyed-Razavi, Y and Lee, SR and Fan, J and Shen, W and Cornish, EE and Gillies, MC},
title = {JR5558 mice are a reliable model to investigate subretinal fibrosis.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {18752},
pmid = {39138242},
issn = {2045-2322},
mesh = {Animals ; *Fibrosis ; *Disease Models, Animal ; Mice ; *Tomography, Optical Coherence/methods ; *Retina/pathology/metabolism ; Receptors, Vascular Endothelial Growth Factor/metabolism ; Fibronectins/metabolism ; Ependymoglial Cells/metabolism/pathology ; Connective Tissue Growth Factor/metabolism/genetics ; Macular Degeneration/pathology/metabolism ; Matrix Metalloproteinase 2/metabolism ; Intravitreal Injections ; Glial Fibrillary Acidic Protein/metabolism ; Actins/metabolism ; Mice, Inbred C57BL ; Recombinant Fusion Proteins ; },
abstract = {Subretinal fibrosis is a major untreatable cause of poor outcomes in neovascular age-related macular degeneration. Mouse models of subretinal fibrosis all possess a degree of invasiveness and tissue damage not typical of fibrosis progression. This project characterises JR5558 mice as a model to study subretinal fibrosis. Fundus and optical coherence tomography (OCT) imaging was used to non-invasively track lesions. Lesion number and area were quantified with ImageJ. Retinal sections, wholemounts and Western blots were used to characterise alterations. Subretinal lesions expand between 4 and 8 weeks and become established in size and location around 12 weeks. Subretinal lesions were confirmed to be fibrotic, including various cell populations involved in fibrosis development. Müller cell processes extended from superficial retina into subretinal lesions at 8 weeks. Western blotting revealed increases in fibronectin (4 wk and 8 wk, p < 0.001), CTGF (20 wks, p < 0.001), MMP2 (12 wks and 20 wks p < 0.05), αSMA (12 wks and 20 wks p < 0.05) and GFAP (8 wk and 12 wk, p ≤ 0.01), consistent with our immunofluorescence results. Intravitreal injection of Aflibercept reduced subretinal lesion growth. Our study provides evidence JR5558 mice have subretinal fibrotic lesions that grow between 4 and 8 weeks and confirms this line to be a good model to study subretinal fibrosis development and assess treatment options.},
}
@article {pmid39136959,
year = {2024},
author = {Wang, S and Liu, Y and Xu, D and Pei, K and Jiang, H and Gong, L and Zeng, W and Liu, Y and Wu, S},
title = {Effects of Topic Delivery of an Inhibitor of Serine Racemase on Laser-Induced Choroidal Vasculopathy.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {8},
pages = {24},
pmid = {39136959},
issn = {2164-2591},
mesh = {Animals ; *Macaca mulatta ; *Choroidal Neovascularization/drug therapy/pathology ; *Disease Models, Animal ; Mice ; *Tomography, Optical Coherence ; *Fluorescein Angiography ; *Mice, Inbred C57BL ; Racemases and Epimerases/antagonists &amp; inhibitors/genetics/metabolism ; Laser Coagulation/adverse effects ; Ophthalmic Solutions ; Male ; Choroid/drug effects/pathology/diagnostic imaging ; Enzyme Inhibitors/pharmacology/administration &amp; dosage/therapeutic use ; Hydroxamic Acids/administration &amp; dosage/pharmacology/therapeutic use ; },
abstract = {PURPOSE: Intravitreal injection of anti-VEGF antibodies remains the primary therapy for exudative age-related macular degeneration (exAMD), although its efficacy is limited. Previous research has demonstrated that both a loss-of-function mutation of srr and the intravenous injection of a serine racemase inhibitor, L-aspartic acid β-hydroxamate (L-ABH), significantly inhibit laser-induced choroidal neovascularization (CNV) in mice. Given that L-ABH is a small molecule, this study investigated the effects of L-ABH administered via eye drops on CNV, aiming to develop a noninvasive treatment strategy for exAMD.<br><br>METHODS: CNV models in mice and rhesus macaques were established through laser photocoagulation. Seven monkeys were randomly assigned to receive either saline solution or L-ABH eye drops. Intraperitoneal or intravenous injection of fluorescein characterized CNV in both mice and monkeys. Fluorescein fundus angiography was used to assess leakage, whereas optical coherence tomography measured retinal thickness in the monkeys.<br><br>RESULTS: L-ABH eye drops significantly reduced fluorescein leakage in laser-injured mice (P < 0.001 compared to saline). In laser-injured rhesus macaques, the average percent changes in leakage areas treated with L-ABH were 2.5% &#xb1; 25.8% (P = 0.004) and 1.5% &#xb1; 75.7% (P = 0.023 compared to saline solution) on day 14 and day 28, respectively. However, L-ABH eye drops did not significantly affect the number of grade IV laser spots or retinal thickness, whereas bevacizumab did.<br><br>CONCLUSIONS: This study demonstrates the potential efficacy of an SRR inhibitor in two animal models of laser-induced CNV.<br><br>TRANSLATIONAL RELEVANCE: This represents the first investigation into the effects of topical delivery of an SRR inhibitor on CNV.},
}
@article {pmid39135029,
year = {2024},
author = {Icoz, M and Gurturk Icoz, SG},
title = {Importance of optical coherence tomography before cataract surgery.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {339},
pmid = {39135029},
issn = {1471-2415},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Aged ; Middle Aged ; Male ; Female ; Aged, 80 and over ; *Cataract Extraction ; *Retinal Diseases/diagnosis/diagnostic imaging ; Adult ; Visual Acuity ; Cataract/diagnosis/complications/diagnostic imaging ; Preoperative Care/methods ; },
abstract = {PURPOSE: To determine the importance of optical coherence tomography (OCT) in patients scheduled for cataract surgery who present with no pathologies in biomicroscopic fundus examination.<br><br>DESIGN: Retrospective study.<br><br>METHODS: In this study, the routine ophthalmologic examination of patients who were recommended cataract surgery was performed.Occult retinal pathologies were evaluated using OCT in patients without any pathologies in biomicroscopic fundus examination.According to whether retinal pathologies were detected on OCT, the patients were divided into two groups: normal and abnormal OCT.The findings of patients with retinal pathologies on OCT and their distribution according to age were also evaluated.<br><br>RESULTS: A total of 271 eyes from 271 patients were evaluated.The number of patients with retinal pathologies on OCT despite normal fundoscopic examination findings was 38(14.0%).Of these patients,15(39.4%) had an epiretinal membrane,10(26.3%) had age-related macular degeneration, eight(21%) had vitreomacular traction, two(5.2%) had a lamellar hole, and 1(2.6%) patient each had a full-thickness macular hole, an intraretinal cyst, and photoreceptor layer damage.The age distribution of the patients with retinal pathologies was as follows: two patients,<60 years; six patients,60-70 years;14 patients,70-80 years; and 16 patients,>80 years.The rate of patients aged&#x2009;>&#x2009;70 years and above was 78.9%.There was no statistically significant difference between the normal and abnormal OCT groups in terms of age, gender, the presence of systemic diseases, visual acuity, central macular thickness, and cataract type or density(p&#x2009;>&#x2009;0.05 for all).<br><br>CONCLUSION: In one of seven patients evaluated, retinal pathologies were detected on OCT despite normal fundoscopic examination findings.OCT can be used to detect occult retinal pathologies that cannot be detected by biomicroscopic fundus examination before cataract surgery.},
}
@article {pmid39134384,
year = {2025},
author = {Taylor, JR and Drinkwater, J and Sousa, DC and Shah, V and Turner, AW},
title = {Real-world evaluation of RetCAD deep-learning system for the detection of referable diabetic retinopathy and age-related macular degeneration.},
journal = {Clinical &amp; experimental optometry},
volume = {108},
number = {5},
pages = {601-606},
doi = {10.1080/08164622.2024.2385565},
pmid = {39134384},
issn = {1444-0938},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Australia/epidemiology ; *Deep Learning ; *Diabetic Retinopathy/diagnosis ; Fundus Oculi ; *Macular Degeneration/diagnosis ; Retrospective Studies ; ROC Curve ; Rural Population ; Sensitivity and Specificity ; },
abstract = {CLINICAL RELEVANCE: The challenges of establishing retinal screening programs in rural settings may be mitigated by the emergence of deep-learning systems for early disease detection.<br><br>BACKGROUND: Deep-learning systems have demonstrated promising results in retinal disease detection and may be particularly useful in rural settings where accessibility remains a barrier to equitable service provision. This study aims to evaluate the real-world performance of Thirona RetCAD for the detection of referable diabetic retinopathy and age-related macular degeneration in a rural Australian population.<br><br>METHODS: Colour fundus images from participants with known diabetic retinopathy or age-related macular degeneration were randomly selected from ophthalmology clinics in four rural Australian centres. Grading was confirmed retrospectively by two retinal specialists. RetCAD produced a quantitative measure (0-100) for DR and AMD severity. The area under the ROC curve (AUC) was calculated. Sensitivity, specificity, and positive and negative predictive values were calculated at a pre-defined cut-point of&#x2009;&#x2265;50.<br><br>RESULTS: A total of 150 images from 82 participants were included. The mean age (SD) was 64.0 (12.8) years. Seventy-nine (52.7%) eyes had evidence of referable DR, while 54 (36.0%) had evidence of referable AMD. The AUC for referable DR detection was 0.971 (95% CI 0.950-0.936) with a sensitivity of 86.1% (76.8%-92.0%) and a specificity of 91.6% (82.8%-96.1%) at the pre-defined cut-point. Using the Youden Index method, the optimal cut-point was 41.2 (sensitivity 93.7%, specificity 90.1%). The AUC for the detection of referable AMD was 0.880 (0.824-0.936). At the pre-defined cut-point sensitivity was 88.9% (77.8%-94.8%) and specificity was 66.7% (56.8%-75.3%). The optimal cut-point was 52.6 (sensitivity 87.0%, specificity 75.0%).<br><br>CONCLUSION: RetCAD is comparable with but does not outperform equivalent deep-learning systems for retinal disease detection. RetCAD may be suitable as an automated screening tool in a rural Australian setting.},
}
@article {pmid39134258,
year = {2025},
author = {Ben Ghezala, I and Gabrielle, PH and Sibert, M and Steinberg, LA and Dautriche, A and Arnould, L and Creuzot-Garcher, C},
title = {Severe Intraocular Inflammation After Intravitreal Injection of Faricimab: A Single-Site Case Series of Six Patients.},
journal = {American journal of ophthalmology},
volume = {269},
number = {},
pages = {11-19},
doi = {10.1016/j.ajo.2024.08.008},
pmid = {39134258},
issn = {1879-1891},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Endophthalmitis/diagnosis/chemically induced ; *Intravitreal Injections ; Retrospective Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {PURPOSE: To describe the patient characteristics and clinical course of severe intraocular inflammation (IOI) following intravitreal injection (IVT) of faricimab.<br><br>DESIGN: Retrospective case series.<br><br>METHODS: Case series at a single French academic center (Dijon University Hospital) where 263 patients were treated with faricimab IVT between January 9, 2024 and May 7, 2024.<br><br>RESULTS: Over the 4-month period, a total of 1659 eyes (1338 patients) received anti-vascular endothelial growth factor (anti-VEGF) IVTs for a total of 3510 IVTs, of which 343 eyes (263 patients) received faricimab IVTs for a total of 971 IVTs. Overall, 6 pretreated eyes with neovascular age-related macular degeneration that were switched to faricimab developed severe unilateral IOI following faricimab IVT (1/162 injections [0.62%]), including 5 eyes presenting with a severe anterior and intermediate uveitis mimicking infectious endophthalmitis. All eyes were normotensive and presented with mild to moderate pain and predominantly moderate vitritis, associated with granulomatous keratic precipitates in 2 eyes and nonocclusive vasculitis in one eye. The clinical presentation, sterile vitreous sample culture, and rapid improvement with treatment made the diagnosis of infectious endophthalmitis unlikely. Four patients out of 6 did not recover their pre-IOI visual acuity, with an average visual loss of +0.2 logMAR. Two patients had positive antinuclear antibodies, including one with a history of cutaneous lupus.<br><br>CONCLUSIONS: In this case series, we reported 6 cases of severe IOI after intravitreal faricimab over 4 months in a single French center with an estimated incidence rate of 0.6% per injection. Future real-world data will contribute to a better evaluation of the epidemiology of this rare inflammatory adverse event related to intravitreal faricimab.},
}
@article {pmid39133415,
year = {2024},
author = {Kubin, AM and Korva-Gurung, I and Ohtonen, P and Hautala, N},
title = {Health-related quality of life in patients with neovascular age-related macular degeneration: a prospective cohort study.},
journal = {Journal of patient-reported outcomes},
volume = {8},
number = {1},
pages = {89},
pmid = {39133415},
issn = {2509-8020},
mesh = {Humans ; *Quality of Life ; Male ; Female ; Aged ; Prospective Studies ; *Visual Acuity/drug effects ; *Angiogenesis Inhibitors/therapeutic use/adverse effects ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Macular Degeneration/drug therapy/physiopathology ; Surveys and Questionnaires ; Wet Macular Degeneration/drug therapy/physiopathology/psychology ; Cohort Studies ; },
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a common cause of visual impairment and blindness in the elderly with globally increasing prevalence. Vascular endothelial growth factor inhibitor (anti-VEGF) treatment has improved visual prognosis of nAMD, but continuous treatment may cause anxiety and stress, although increase in visual acuity (VA) may also have positive effects on patients' quality of life. The health care burden due to frequent treatment and monitoring is apparent, but the effect of anti-VEGF treatment on patients' quality of life is not fully understood. We evaluated the overall impact of nAMD and its treatment on newly diagnosed patients' health-related quality of life (HRQoL) in real-world setting.<br><br>METHODS: The present prospective cohort study included newly diagnosed nAMD patients treated with anti-VEGF injections at Oulu University Hospital during 2019-2020. Data included parameters from comprehensive ophthalmic examination and fundus imaging, age at diagnosis, sex, comorbidities, visual acuity, and frequency of anti-VEGF injections. HRQoL was assessed by 15D questionnaire at diagnosis, 6 months, and 12 months.<br><br>RESULTS: 95 nAMD patients were included. They were 78&#x2009;&#xb1;&#x2009;8 years old, 56 (59%) were female, and 74 (78%) had more than one comorbidity. The patients received 8&#x2009;&#xb1;&#x2009;3 anti-VEGF-injections. Visual acuity (VA) improved from 56&#x2009;&#xb1;&#x2009;18 to 61&#x2009;&#xb1;&#x2009;24 Early treatment diabetic retinopathy study (ETDRS) letters in 12 months. VA improved&#x2009;>&#x2009;5 ETDRS letters in 45 (47%), remained stable in 30 (32%) and decreased&#x2009;>&#x2009;5 letters in 17 (18%) eyes. The mean total 15D score reflecting overall HRQoL decreased from 0.850&#x2009;&#xb1;&#x2009;0.104 to 0.834&#x2009;&#xb1;&#x2009;0.103 in 12 months. Decreased HRQoL was associated with baseline best-corrected VA (BCVA)&#x2009;&#x2265;&#x2009;70 ETDRS letters (p&#x2009;=&#x2009;0.023) and more than one comorbidity (p&#x2009;=&#x2009;0.034). HRQoL regarding visual function increased from 0.765&#x2009;&#xb1;&#x2009;0.194 to 0.789&#x2009;&#xb1;&#x2009;0.184 during the 12-month follow-up.<br><br>CONCLUSIONS: In real world setting, HRQoL regarding visual function improved in anti-VEGF-treated nAMD patients during the first 12 months after the diagnosis and treatment initiation. Good baseline VA or several comorbidities were associated with decreased overall HRQoL during the follow-up. Despite the effectiveness of anti-VEGF treatment on visual function, several other aspects affecting elderly patients' everyday life should be considered when nAMD treatment is implemented.},
}
@article {pmid39133375,
year = {2024},
author = {Kim, YH and Moon, TK and Ji, YS},
title = {Factors Affecting Disease Stability After Intravitreal Brolucizumab Injection for Refractory Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {10},
pages = {2679-2695},
pmid = {39133375},
issn = {2193-8245},
abstract = {INTRODUCTION: The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment.<br><br>METHODS: We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE&#x2009;<&#x2009;12&#xa0;weeks (N&#x2009;=&#x2009;16) and group 2 with TE&#x2009;&#x2265;&#x2009;12&#xa0;weeks (N&#x2009;=&#x2009;15). We compared outcomes between the groups at 2, 4, 8, and 12&#xa0;weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE&#x2009;&#x2265;&#x2009;12&#xa0;weeks.<br><br>RESULTS: Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2&#xa0;weeks (P&#x2009;<&#x2009;0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8&#xa0;&#x3bc;m; P&#x2009;<&#x2009;0.05), 4 (224.0 vs. 262.9&#xa0;&#x3bc;m; P&#x2009;<&#x2009;0.05), and 8&#xa0;weeks (216.8 vs. 331.1&#xa0;&#x3bc;m; P&#x2009;<&#x2009;0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm[2]; P&#x2009;<&#x2009;0.05) and total vessel length (0.22 vs. 0.42&#xa0;mm; P&#x2009;<&#x2009;0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P&#x2009;<&#x2009;0.05). Dry macula at 2&#xa0;weeks (odds ratio [OR]&#x2009;=&#x2009;8.3; P&#x2009;<&#x2009;0.05) and a lower CCFd (OR&#x2009;=&#x2009;0.73; P&#x2009;<&#x2009;0.05) were associated with TE&#x2009;&#x2265;&#x2009;12&#xa0;weeks.<br><br>CONCLUSIONS: Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.},
}
@article {pmid39133226,
year = {2024},
author = {Carlà, MM and Giannuzzi, F and Boselli, F and Crincoli, E and Rizzo, S},
title = {Extensive macular atrophy with pseudodrusen-like appearance: comprehensive review of the literature.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {10},
pages = {3085-3097},
pmid = {39133226},
issn = {1435-702X},
mesh = {Humans ; *Retinal Drusen/diagnosis/etiology ; *Tomography, Optical Coherence/methods ; *Macula Lutea/pathology ; *Fluorescein Angiography/methods ; Fundus Oculi ; Retinal Pigment Epithelium/pathology ; Visual Acuity ; Macular Degeneration/diagnosis/etiology/complications ; Atrophy ; },
abstract = {PURPOSE: This review focuses on extensive macular atrophy with pseudodrusen-like appearance (EMAP), a recently described maculopathy presenting with pseudodrusen-like lesions and chorioretinal atrophy more pronounced in the vertical axis.<br><br>METHODS: Narrative review of the literature published until May 2024.<br><br>RESULTS: The early onset age of EMAP (50-55 years) and its distinctive natural history, which includes night blindness followed by severe vision loss, differentiate it from atrophic age-related macular degeneration (AMD). A clear pathogenesis has not been determined, but risk factors include female gender and complement system abnormalities (altered levels of C3 and CH50). Moreover, lifelong exposure to pesticides has been suggested as risk factor for direct neuronal degeneration involving rods and cones. In the early phase of the disease, reticular pseudodrusen-like lesions appear in the superior perifovea and tend to coalescence horizontally into a flat, continuous, reflective material localized between the retinal pigmented epithelium and Bruch's membrane. Over time, EMAP causes profound RPE and outer retinal atrophy in the macular area, with a recent classification reporting a 3-stages evolution pattern. Blue autofluorescence showed rapidly evolving atrophy with either hyperautofluorescent or isoautofluorescent borders. Significant similarities between the diffuse-trickling phenotype of geographic atrophy and EMAP have been reported. Macular neovascularization is a possible complication.<br><br>CONCLUSION: EMAP is specific form of early-onset atrophic macular degeneration with rapid evolution and no treatment. Further studies are needed to assess the best management.},
}
@article {pmid39133039,
year = {2024},
author = {Jiménez-Loygorri, JI and Boya, P},
title = {Recycling the recyclers: lysophagy emerges as a new pharmacological target for retinal degeneration.},
journal = {Autophagy},
volume = {20},
number = {11},
pages = {2589-2590},
pmid = {39133039},
issn = {1554-8635},
mesh = {Humans ; *Lysosomes/metabolism/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Animals ; Retinal Degeneration/pathology/drug therapy/metabolism ; Mitophagy/drug effects/physiology ; Autophagy/drug effects/physiology ; Macular Degeneration/pathology/drug therapy/metabolism ; Sequestosome-1 Protein/metabolism ; Iodates ; },
abstract = {Dysregulated macroautophagy/autophagy is one of the hallmarks of aging and has also been linked to higher incidence of several age-associated diseases such as age-related macular degeneration (AMD). The main cell type affected in AMD is the retinal pigment epithelium (RPE), and this disease can lead to central vision loss. Despite affecting around 8.7% of the population between 45-85 years, its etiopathogenesis remains unknown. In our recent manuscript using the pharmacological sodium iodate (SI) model of AMD we identified severe lysosomal membrane permeabilization (LMP) in the RPE, that leads to autophagy flux blockage and proteostasis defects. Treatment with the natural compound urolithin A (UA) reduces RPE cell death and alleviates vision loss, concurrent with full autophagy restoration. While UA was initially described as a specific mitophagy inducer, we now show that it is also able to promote SQSTM1/p62-dependent lysophagy in the context of lysosomal damage and LMP. Genetic downregulation of SQSTM1/p62 fully abolishes the effect of UA on lysophagy while mitophagy stimulation remains unaffected. In summary, these findings highlight the wide range of pathways modulated by UA and its potential implementation in the management of AMD and other diseases involving lysosomal damage.},
}
@article {pmid39130992,
year = {2024},
author = {Alomari, A and Issa, S and Abusamak, M},
title = {Elderly Patient With Bilateral Central Serous Chorioretinopathy Misdiagnosed as Bilateral Wet Age-Related Macular Degeneration: A Case Report.},
journal = {Cureus},
volume = {16},
number = {7},
pages = {e64210},
pmid = {39130992},
issn = {2168-8184},
abstract = {This report presents a unique case of a 77-year-old diabetic male patient with bilateral central serous chorioretinopathy (CSCR), who was receiving multiple bilateral intravitreal injections for a presumed diagnosis of wet age-related macular degeneration (AMD). The fundus examination did not show any signs of AMD or diabetic retinopathy (DR). The spectral domain optical coherence tomography (OCT) revealed bilateral subretinal fluid. The neovascular membrane was not visible on OCT angiography. Fundus fluorescein angiography (FFA) confirmed the absence of choroidal neovascularization (CNV). Notably, this represents a unique case of an elderly patient with CSCR mimicking occult CNV.},
}
@article {pmid39129350,
year = {2024},
author = {Huang, K and Deng, H and Wang, S and Zhang, F and Huang, G and Wang, L and Liu, J and Zhao, X and Ren, H and Yang, G and Lin, Z},
title = {Melanin-Like Nanomedicine Functions as a Novel RPE Ferroptosis Inhibitor to Ameliorate Retinal Degeneration and Visual Impairment in Dry Age-Related Macular Degeneration.},
journal = {Advanced healthcare materials},
volume = {13},
number = {30},
pages = {e2401613},
doi = {10.1002/adhm.202401613},
pmid = {39129350},
issn = {2192-2659},
support = {2023028//Chengdu Medical Scientific Research Project/ ; 2022282//Chengdu Medical Scientific Research Project/ ; 2022-YF05-01861-SN//Chengdu Science and Technology Bureau's technology innovation research and development project/ ; 2024-YF05-00901-SN//Chengdu Science and Technology Bureau's technology innovation research and development project/ ; 2023PI23//Third People's Hospital of Chengdu Scientific Research Project/ ; KY2023QN0014//Sichuan Province Science and Technology Support Program/ ; },
mesh = {Animals ; *Ferroptosis/drug effects ; Mice ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Oxidative Stress/drug effects ; Melanins ; Iodates ; Humans ; Retinal Degeneration/drug therapy/metabolism/pathology ; Nanoparticles/chemistry ; Nanomedicine/methods ; Mice, Inbred C57BL ; Macular Degeneration/drug therapy/metabolism/pathology ; Disease Models, Animal ; Electroretinography ; },
abstract = {Ferrous ion accumulation and lethal oxidative stress mediate irreversible retinal pigment epithelial (RPE) cell ferroptosis and subsequent photoreceptor degeneration, a potential key pathogenic factor in the onset of dry age-related macular degeneration (dAMD), causing irreversible vision loss in the global elderly population. However, currently, no effective interventional treatment strategy exists in clinical practice. Herein, lesion site-targeted melanin-like nanoparticles, named ConA-MelNPs, are designed as a novel ferroptosis inhibitor for retinal degenerative diseases. ConA-MelNPs possessed chelating iron ion characteristics, alleviating severe mitochondrial damage caused by oxidative stress and protecting RPE cells from ferroptosis induced by sodium iodate (NaIO3). In a preclinical dAMD mouse model, a single intravitreal injection of ConA-MelNPs yielded significant responses in electroretinograms and visually-driven optomotor responses in visually impaired mice, resisting the challenge posed by secondary NaIO3-induced injuries, with the long-term sustainability of its therapeutic effect. Mechanistically, ConA-MelNPs achieve a therapeutic effect by interrupting the detrimental cascade involving "RPE cell ferroptosis, lethal oxidative stress, and microglial proinflammatory activation," affording the restoration of retinal homeostasis. The synthesized ConA-MelNPs demonstrated good biosafety, with no detected ophthalmic or systemic side effects. Collectively, ConA-MelNPs are proposed as a promising therapeutic option for atrophic retinal diseases such as dAMD.},
}
@article {pmid39129024,
year = {2024},
author = {Cao, Y and Dang, M and Tian, Z and Zhang, T and Hou, L and Wang, M and Xing, S and Huang, Y and Li, J},
title = {Aqueous humor cytokine levels in patients with subretinal fibrosis in neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {335},
pmid = {39129024},
issn = {1471-2415},
support = {2023YJY-26//the Science and Technology development Incubation Foundation of Shaanxi Provincial People's Hospital/ ; 2022JM-517//the Natural Science Foundation of Shaanxi Province/ ; 2021JY-37//the Science and Technology Talents Support Program of Shaanxi Provincial People's Hospital/ ; },
mesh = {Humans ; *Aqueous Humor/metabolism ; Male ; Female ; Aged ; *Fibrosis/metabolism ; *Cytokines/metabolism ; Wet Macular Degeneration/metabolism/diagnosis ; Aged, 80 and over ; Biomarkers/metabolism ; Middle Aged ; Tomography, Optical Coherence/methods ; Visual Acuity ; Fluorescein Angiography ; },
abstract = {PURPOSE: To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity.<br><br>METHODS: The aqueous humor samples were collected from 16 eyes with subretinal fibrosis due to nAMD (SRFi group), 33 eyes with nAMD without subretinal fibrosis (nAMD group) and 28 eyes with cataract patients (control group). Clinical samples were analyzed for 5 cytokines,including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor-&#x3b1; (TGF-&#x3b1;), platelet-derived growth factor-BB (PDGF-BB).<br><br>RESULTS: Aqueous humor cytokines VEGF and bFGF were significantly higher in nAMD patients than controls (all P&#x2009;<&#x2009;0.05), and VEGF, bFGF and TGF-&#x3b1; levels were significantly higher in SRFi patients than controls (all P&#x2009;<&#x2009;0.05). No significant differences in 4 cytokine levels were observed between nAMD and SRFi patients in aqueous humor. We also identified a positive correlation between the aqueous humor levels of IL-6 and VEGF in the SRFi group, while bFGF and TGF-&#x3b1; in the nAMD group. Moreover, VEGF levels were strongly related to BCVA, and bFGF levels were positively related to the maximum thickness of subretinal hyperreflective material (SHRM) in fibrosis due to nAMD.<br><br>CONCLUSION: VEGF and bFGF levels in aqueous humor were elevated in macular neovascularization with and without subretinal fibrosis. TGF-&#x3b1; levels exclusively differed in neovascular AMD with fibrosis. Cytokines are distributed differently and play a synergistic role in different stages (angiogenesis and fibrogenesis) of nAMD. The bFGF levels could predict the negative prognosis in fibrosis due to nAMD.},
}
@article {pmid39128832,
year = {2025},
author = {Ashrafkhorasani, M and Habibi, A and Nittala, MG and Yaseri, M and Emamverdi, M and Velaga, SB and Wykoff, CC and Ciulla, TA and Ip, M and Sadda, SR},
title = {Spectral-domain OCT characteristics of intraretinal hyper-reflective foci associated with age-related macular degeneration and diabetic retinopathy.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {2},
pages = {91-99},
doi = {10.1016/j.jcjo.2024.07.017},
pmid = {39128832},
issn = {1715-3360},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; *Diabetic Retinopathy/diagnosis ; Aged ; Visual Acuity ; Fluorescein Angiography/methods ; Middle Aged ; Nerve Fibers/pathology ; *Macular Degeneration/diagnosis ; Aged, 80 and over ; Fundus Oculi ; },
abstract = {OBJECTIVE: The purpose of this study was to quantitatively analyze and compare OCT characteristics of intraretinal hyper-reflective foci (IHRF) in eyes with diabetic retinopathy (DR) versus age-related macular degeneration (AMD).<br><br>DESIGN: a retrospective observational study.<br><br>PARTICIPANTS: 54 treatment-na&#xef;ve eyes (27 DR and 27 AMD).<br><br>METHODS: The IHRF lesions in OCT B-scan were semi-automatically segmented. Mean reflectivity (MR), maximum diameter, circularity index (Cir), area, and the angle between the greatest linear dimension (GLD) and the horizontal were computed for each IHRF lesion. The presence and absence of a posterior shadow and the axial location were assessed. The MR was normalized using the vitreous and nerve fiber layer reflectance as dark and bright reference standards, respectively.<br><br>RESULTS: A total of 1149 IHRF (1051 in DR and 98 in the AMD group) were identified, with a mean of 39 &#xb1; 36 lesions in DR eyes compared to only 4 &#xb1; 4 in AMD eyes (p < 0.001). The mean area of individual IHRF lesions was greater in DR eyes (1305 &#xb1; 1647 &#x3bc;m&#xb2; vs 1031 &#xb1; 750 &#x3bc;m&#xb2;; p&#x202f;=&#x202f;0.016), but IHRF in AMD eyes had higher reflectivity (1.17 &#xb1; 0.14 vs 1.03 &#xb1; 0.17; p < 0.001). The angle of the GLD relative to the horizontal was greater in AMD eyes, indicating that IHRF in AMD eyes were more horizontally oriented. In AMD eyes, 88.8% of IHRF were located beneath the inner border of the outer nuclear layer (ONL), while in DR eyes, 56.9% were located there (p < 0.001).<br><br>CONCLUSIONS: IHRF lesions in eyes with DR and AMD demonstrate significant differences, with IHRF in DR eyes tending to be larger and less hyper-reflective compared to AMD eyes.},
}
@article {pmid39128809,
year = {2024},
author = {Chen, TE and Lo, J and Huang, SP and Chang, KC and Liu, PL and Wu, HE and Chen, YR and Chang, YC and Liu, CC and Lee, PY and Lai, YH and Wu, PC and Wang, SC and Li, CY},
title = {Glaucine inhibits hypoxia-induced angiogenesis and attenuates LPS-induced inflammation in human retinal pigment epithelial ARPE-19 cells.},
journal = {European journal of pharmacology},
volume = {981},
number = {},
pages = {176883},
doi = {10.1016/j.ejphar.2024.176883},
pmid = {39128809},
issn = {1879-0712},
mesh = {Humans ; *Lipopolysaccharides ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology/pathology ; *Vascular Endothelial Growth Factor A/metabolism ; Cell Line ; *Cell Survival/drug effects ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; *Aporphines/pharmacology ; Inflammation/drug therapy/metabolism/pathology ; Cell Hypoxia/drug effects ; Neovascularization, Pathologic/drug therapy ; Anti-Inflammatory Agents/pharmacology ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Angiogenesis Inhibitors/pharmacology ; Cobalt/toxicity/pharmacology ; Chemokine CCL2/metabolism ; Angiogenesis ; },
abstract = {Glaucine is an aporphine alkaloid with anti-inflammatory, bronchodilator and anti-cancer activities. However, the effects of glaucine in the regulation of age-related macular degeneration (AMD) remain unclear. Herein, we aimed to investigate the anti-angiogenetic and anti-inflammatory effects of glaucine in ARPE-19 cells. ARPE-19 cells were treated with N-(methoxyoxoacetyl)-glycine, methyl ester (DMOG) and cobalt chloride (CoCl2) for induction of hypoxia, while lipopolysaccharide (LPS) treatment was used for elicitation of inflammatory response. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by Western blot. The secretion of VEGF, interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) was detected using enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were used for tube formation analysis. Expression of HIF-1α and secretion of VEGF were significantly increased under DMOG and CoCl2 induction, whereas glaucine significantly attenuated both HIF-1α expression and VEGF secretion by DMOG- and CoCl2-induced ARPE-19 cells. In addition, glaucine suppressed the tube formation by DMOG- and CoCl2-induced HUVEC cells. Moreover, glaucine also attenuated the production of IL-6 and MCP-1 by LPS-induced ARPE-19 cells. This study indicated that glaucine exhibited anti-angiogenic and anti-inflammatory effects, suggesting that glaucine might have benefits for the treatment of AMD.},
}
@article {pmid39128667,
year = {2024},
author = {Wojciechowski, AM and Bell, BA and Song, Y and Anderson, BD and Conomikes, A and Petruconis, C and Dunaief, JL},
title = {Inducible RPE-specific GPX4 knockout causes oxidative stress and retinal degeneration with features of age-related macular degeneration.},
journal = {Experimental eye research},
volume = {247},
number = {},
pages = {110028},
pmid = {39128667},
issn = {1096-0007},
support = {S10 OD026860/OD/NIH HHS/United States ; T32 GM008076/GM/NIGMS NIH HHS/United States ; T32 EY007035/EY/NEI NIH HHS/United States ; R01 EY028916/EY/NEI NIH HHS/United States ; R01 EY015240/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; R01 EY036292/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Female ; Mice ; Disease Models, Animal ; Electroretinography ; *Glutathione Peroxidase/metabolism/genetics ; *Macular Degeneration/genetics/metabolism/pathology ; Mice, Inbred C57BL ; Mice, Knockout ; *Oxidative Stress ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism/genetics ; Retinal Degeneration/metabolism/pathology/genetics ; *Retinal Pigment Epithelium/metabolism/pathology/ultrastructure ; Tomography, Optical Coherence ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. This disease involves oxidative stress burden in the retina leading to death of retinal pigment epithelial (RPE) cells and photoreceptors. The retina is susceptible to oxidative stress, in part due to high metabolic activity and high concentration of polyunsaturated fatty acids that undergo lipid peroxidation chain reactions. Antioxidant enzymes exist in the retina to combat this stress, including glutathione peroxidase 4 (GPX4). GPX4 specifically reduces oxidized lipids, protecting against lipid peroxidation-induced oxidative stress, which is noted in dry AMD. We hypothesize that Gpx4 knockout within the RPE will result in an environment of chronic oxidative stress yielding degeneration akin to AMD. C57BL/6J mice with a floxed Gpx4 gene were mated with Rpe65Cre/ER mice. Offspring containing Rpe65Cre ± alleles and either Gpx4 WT or Gpx4 fl/fl alleles were administered tamoxifen to induce Gpx4 knockout in Gpx4 fl/fl mice. At sequential timepoints, retinal phenotypes were assessed via in vivo imaging utilizing confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT), and visual function was probed by electroretinography. Retinas were studied post-mortem by immunohistochemical analyses, electron microscopy, plastic sectioning, and quantitative polymerase chain reaction and Western analyses. The RPE-specific Gpx4 knockout model was validated via Western analysis indicating diminished GPX4 protein only within the RPE and not the neural retina. Following Gpx4 knockout, RPE cells became dysfunctional and died, with significant cell loss occurring 2 weeks post-knockout. Progressive thinning of the photoreceptor layer followed RPE degeneration and was accompanied by loss of visual function. OCT and light microscopy showed hyperreflective foci and enlarged, pigmented cells in and above the RPE layer. Electron microscopy revealed decreased mitochondrial cristae and loss of basal and apical RPE ultrastructure. Finally, there was increased carboxyethylpyrrole staining, indicating oxidation of docosahexaenoic acid, and increased levels of mRNAs encoding oxidative stress-associated genes in the RPE and photoreceptors. Overall, we show that RPE-localized GPX4 is necessary for the health of the RPE and outer retina, and that knockout recapitulates phenotypes of dry AMD.},
}
@article {pmid39127778,
year = {2024},
author = {Brown, EE and Guy, AA and Holroyd, NA and Sweeney, PW and Gourmet, L and Coleman, H and Walsh, C and Markaki, AE and Shipley, R and Rajendram, R and Walker-Samuel, S},
title = {Physics-informed deep generative learning for quantitative assessment of the retina.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {6859},
pmid = {39127778},
issn = {2041-1723},
support = {C44767/A29458//Cancer Research UK (CRUK)/ ; EP/W007096/1//RCUK | Engineering and Physical Sciences Research Council (EPSRC)/ ; },
mesh = {Humans ; *Deep Learning ; *Retinal Vessels/diagnostic imaging ; *Retina/diagnostic imaging ; *Algorithms ; Image Processing, Computer-Assisted/methods ; Diabetic Retinopathy/diagnosis ; Macular Degeneration/pathology ; },
abstract = {Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading to vision loss. We present here a novel algorithmic approach that generates highly realistic digital models of human retinal blood vessels, based on established biophysical principles, including fully-connected arterial and venous trees with a single inlet and outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation and reconstruction of blood vessel networks with no human input and which out-performs human labelling. Segmentation of DRIVE and STARE retina photograph datasets provided near state-of-the-art vessel segmentation, with training on only a small (n = 100) simulated dataset. Our findings highlight the potential of PI-GAN for accurate retinal vasculature characterization, with implications for improving early disease detection, monitoring disease progression, and improving patient care.},
}
@article {pmid39126559,
year = {2024},
author = {Yanagi, Y and Takahashi, K and Iida, T and Gomi, F and Onishi, H and Morii, J and Sakamoto, T},
title = {Cost-effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration and its Subtypes from the Societal and Patient Perspectives in Japan.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {10},
pages = {2629-2644},
pmid = {39126559},
issn = {2193-8245},
abstract = {INTRODUCTION: This study evaluated the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) therapies for subtypes of neovascular age-related macular degeneration (nAMD) from the societal perspective, and for any nAMD from the patient perspective in Japan.<br><br>METHODS: A Markov model was developed to simulate the lifetime transitions of a cohort of patients with nAMD through various health states based on the involvement of nAMD, the treatment status, and decimal best-corrected visual acuity. Ranibizumab biosimilar was compared with aflibercept from the societal perspective regardless of treatment regimen for the analysis of three subtypes (typical nAMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)). Two analyses from the patient perspective focusing on the treat-and-extend regimens were performed, one with a cap on patients' copayments and one without. Ranibizumab biosimilar was compared with branded ranibizumab, aflibercept, aflibercept as the loading dose switching to ranibizumab biosimilar during maintenance (aflibercept switching to ranibizumab biosimilar), and best supportive care (BSC), for patients with any nAMD.<br><br>RESULTS: In the subtype analyses, ranibizumab biosimilar when compared with aflibercept resulted in incremental quality-adjusted life years (QALYs) of -&#x2009;0.015, 0.026, and 0.009, and the incremental costs of Japanese yen (JPY) -&#x2009;50,447, JPY -&#x2009;997,243, and JPY -&#x2009;1,286,570 for typical nAMD, PCV, and RAP, respectively. From the patient perspective, ranibizumab biosimilar had incremental QALYs of 0.015, 0.009, and 0.307, compared with aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. The incremental costs for ranibizumab biosimilar over a patient lifetime excluding the cap on copayment were estimated to be JPY -&#x2009;138,948, JPY -&#x2009;391,935, JPY -&#x2009;209,099, and JPY -&#x2009;6,377,345, compared with branded ranibizumab, aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively.<br><br>CONCLUSIONS: Ranibizumab biosimilar was demonstrated as a cost-saving option compared to aflibercept across all subtypes of nAMD, irrespective of the perspectives considered.},
}
@article {pmid39125641,
year = {2024},
author = {Hernandez, M and Recalde, S and Bezunartea, J and Moreno-Orduña, M and Belza, I and Chas-Prat, A and Perugini, E and Garcia-Layana, A and Fernández-Robredo, P},
title = {The Scavenging Activity of Coenzyme Q10 Plus a Nutritional Complex on Human Retinal Pigment Epithelial Cells.},
journal = {International journal of molecular sciences},
volume = {25},
number = {15},
pages = {},
pmid = {39125641},
issn = {1422-0067},
support = {Thea Laboratories//Thea Laboratories/ ; },
mesh = {Humans ; *Ubiquinone/analogs &amp; derivatives/pharmacology ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Oxidative Stress/drug effects ; *Apoptosis/drug effects ; *Hydrogen Peroxide/metabolism/pharmacology ; Mitochondria/metabolism/drug effects ; Antioxidants/pharmacology ; Epithelial Cells/metabolism/drug effects ; Cell Line ; Dietary Supplements ; },
abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total[®]; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1β, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1β gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR.},
}
@article {pmid39125491,
year = {2024},
author = {Raghavendra, AJ and Elhusseiny, AM and Agrawal, A and Liu, Z and Hammer, DX and Saeedi, OJ},
title = {Compact Linear Flow Phantom Model for Retinal Blood-Flow Evaluation.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {15},
pages = {},
pmid = {39125491},
issn = {2075-4418},
support = {R01 EY031731/EY/NEI NIH HHS/United States ; M-CERSI//United States Food and Drug Administration/ ; R01EY031731//National Eye In-318 stitute/National Institutes of Health/ ; },
abstract = {Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood cells and provides a high resolution with which to measure flow across retinal microvasculature. However, cross-validation of flow measures remains a challenge owing to instrument and patient-specific variability in each imaging technique. Hence, there is a critical need for a well-controlled clinical flow phantom for standardization and to establish blood-flow measures as clinical biomarkers for early diagnosis. Here, we present the design and validation of a simple, compact, portable, linear flow phantom based on a direct current motor and a conveyor-belt system that provides linear velocity tuning within the retinal microvasculature range (0.5-7 mm/s). The model was evaluated using a sensitive AO-SLO line-scan technique, which showed a <6% standard deviation from the true velocity. Further, a clinical SLO instrument showed a linear correlation with the phantom's true velocity (r[2] > 0.997). This model has great potential to calibrate, evaluate, and improve the accuracy of existing clinical imaging systems for retinal blood flow and aid in the diagnosis of ocular diseases with abnormal blood flow.},
}
@article {pmid39124642,
year = {2024},
author = {Hirayama, K and Yamamoto, M and Honda, S and Kyo, A and Misawa, N and Kohno, T},
title = {Switching to Intravitreal Brolucizumab after Ranibizumab or Aflibercept Using Treat and Extend Regimen for Neovascular Age-Related Macular Degeneration in Japanese Patients: 1-Year Results and Factors Associated with Treatment Responsiveness.},
journal = {Journal of clinical medicine},
volume = {13},
number = {15},
pages = {},
pmid = {39124642},
issn = {2077-0383},
abstract = {Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903-0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013-0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept.},
}
@article {pmid39124583,
year = {2024},
author = {Chujo, S and Matsubara, H and Mase, Y and Kato, K and Kondo, M},
title = {Recurrence Rate during 5-Year Period after Suspension of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {15},
pages = {},
pmid = {39124583},
issn = {2077-0383},
abstract = {Purpose: To determine the recurrence rate of neovascular age-related macular degeneration (nAMD) during a 5-year period after the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments. Methods: Thirty-four eyes of 34 nAMD patients who met the inclusion criteria and were treated by anti-VEGF drugs were studied. All met the treatment suspension criteria and were followed for 5 years after the suspension of the anti-VEGF treatment. Patients with a recurrence within one year were placed in Group A, and patients with a recurrence between 1 and 5 years were placed in Group B. The rate and time of a recurrence were analyzed using the Kaplan-Meier method. We also examined whether there were differences in the baseline factors of age, sex, subtype, treatment period, and treatment interval between Groups A and B. Results: Twenty-five of 34 eyes (73.5%) had a recurrence within 5 years of stopping the anti-VEGF treatments. Thirteen (52.0%) of the 25 eyes had a recurrence within 1 year, 4 (16.0%) eyes between 1 and 2 years, 4 (16.0%) eyes between 2 and 3 years, 2 (8%) between 3 and 4 years, and 2 eyes (8%) between 4 and 5 years. The baseline factors were not significantly different between Groups A and B. Conclusions: The results showed that the recurrence rate was highest within one year after the suspension of the anti-VEGF treatments, with a number of recurrences one year after the suspension. Clinicians should remember that nAMD may recur several years after the suspension of anti-VEGF treatments.},
}
@article {pmid39122890,
year = {2024},
author = {Ozturk, E and Cankaya, C and Yildizli, Y},
title = {Correlation between corneal endothelial layer features and age-related macular degeneration severity.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {345},
pmid = {39122890},
issn = {1573-2630},
mesh = {Humans ; Male ; Female ; *Endothelium, Corneal/pathology ; Aged ; *Severity of Illness Index ; Cell Count ; *Macular Degeneration/diagnosis/pathology ; Middle Aged ; Aged, 80 and over ; Visual Acuity ; Tomography, Optical Coherence/methods ; Retrospective Studies ; },
abstract = {PURPOSE: This study aimed to investigate the relationship between corneal endothelial layer features and the severity of age-related macular degeneration (AMD).<br><br>METHODS: The study included 119 patients, with 47 females and 72 males. Patients were categorized into four groups based on the AREDS grading system: no AMD (group 1), mild AMD (group 2), moderate AMD (group 3), and advanced AMD (group 4). Only the right eye of patients with both eyes suitable for the study was included. Corneal endothelial cell density (CD), coefficient of variation (CoV), hexagonal cell ratio (HEX), and central corneal thickness (CCT) were measured using specular microscopy (Konan Medical Inc., Nishinomiya, Japan).<br><br>RESULTS: Group 1 had 40 patients, group 2 had 27 patients, and groups 3 and 4 had 26 patients each. Significant differences were observed between the mean endothelial CD, CoV, and HEX values among the groups, while no significant difference was found in CCT values (p&#x2009;=&#x2009;0.049, p&#x2009;=&#x2009;0.002, p&#x2009;=&#x2009;0.004, and p&#x2009;=&#x2009;0.883, respectively). A mild negative correlation was observed between AMD severity and CD and HEX values, while a mild positive correlation was found between AMD severity and CoV.<br><br>CONCLUSION: Increasing severity of AMD may negatively impact corneal endothelial layer values.},
}
@article {pmid39122857,
year = {2024},
author = {Veritti, D and Sarao, V and Gonfiantini, M and Rubinato, L and Lanzetta, P},
title = {Faricimab in Neovascular AMD Complicated by Pigment Epithelium Detachment: An AI-Assisted Evaluation of Early Morphological Changes.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {10},
pages = {2813-2824},
pmid = {39122857},
issn = {2193-8245},
abstract = {INTRODUCTION: This study investigates the early temporal changes in pigment epithelial detachment (PED) morphology following treatment with faricimab in patients with neovascular age-related macular degeneration (nAMD). Utilizing an artificial intelligence (AI)-assisted approach, we provide a detailed quantification and characterization of the dynamics of these morphological changes.<br><br>METHODS: A prospective observational study was conducted on 22 eyes from 22 treatment-na&#xef;ve patients with nAMD-associated PED (presenting either type 1 or type 3 macular neovascularization). Participants were administered intravitreal faricimab (6&#xa0;mg) at baseline and at days 30, 60, and 90. Comprehensive ophthalmic evaluations and spectral-domain optical coherence tomography (SD-OCT) imaging were conducted at baseline and at seven additional follow-up visits on days 1, 7, 14, 30, 60, 90, and 120. An AI-based automated segmentation algorithm was utilized to precisely quantify changes in PED volume, alongside intraretinal (IRF) and subretinal fluid (SRF) volumes, at each time point.<br><br>RESULTS: Treatment with faricimab resulted in a significant reduction in mean PED volume, with an average decrease of 12% at day 1, 29% at day 7, 51% at day 14, 68% at day 30, 72% at day 60, 79% at day 90, and 84% at day 120 (p&#x2009;<&#x2009;0.0001 for all time points). Similarly rapid and marked reductions were noted in both mean IRF (23.5% at day 1, 90.7% at day 14) and SRF (14.4% at day 1, 91.2% at day 14) volumes. The study also showed a statistically significant improvement in best-corrected visual acuity (BCVA) over the follow-up period, correlating with the reduction in PED volume.<br><br>CONCLUSION: Faricimab demonstrates early and significant efficacy in improving PED architecture in patients with nAMD. The rapid morphological improvements observed in this study suggest faricimab may represent a valid therapeutic option for PEDs associated with nAMD.},
}
@article {pmid39122684,
year = {2024},
author = {Kim, J and Jeon, Y and Son, J and Pagire, HS and Pagire, SH and Ahn, JH and Uemura, A and Lee, IK and Park, S and Park, DH},
title = {PDK4-mediated metabolic reprogramming is a potential therapeutic target for neovascular age-related macular degeneration.},
journal = {Cell death &amp; disease},
volume = {15},
number = {8},
pages = {582},
pmid = {39122684},
issn = {2041-4889},
support = {RS-2021-DD120784//Korea Drug Development Fund (KDDF)/ ; HR22C1832//Korea Health Industry Development Institute (KHIDI)/ ; },
mesh = {Animals ; Humans ; Mice ; *Macular Degeneration/metabolism/pathology ; *Choroidal Neovascularization/metabolism/pathology/drug therapy ; *Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *Disease Models, Animal ; Mice, Inbred C57BL ; Mitochondria/metabolism/drug effects ; Oxidative Phosphorylation/drug effects ; Metabolic Reprogramming ; },
abstract = {Age-related macular degeneration (AMD) causes severe blindness in the elderly due to choroidal neovascularization (CNV), which results from the dysfunction of the retinal pigment epithelium (RPE). While normal RPE depends exclusively on mitochondrial oxidative phosphorylation for energy production, the inflammatory conditions associated with metabolic reprogramming of the RPE play a pivotal role in CNV. Although mitochondrial pyruvate dehydrogenase kinase (PDK) is a central node of energy metabolism, its role in the development of CNV in neovascular AMD has not been investigated. In the present study, we used a laser-induced CNV mouse model to evaluate the effects of Pdk4 gene ablation and treatment with pan-PDK or specific PDK4 inhibitors on fluorescein angiography and CNV lesion area. Among PDK isoforms, only PDK4 was upregulated in the RPE of laser-induced CNV mice, and Pdk4 gene ablation attenuated CNV. Next, we evaluated mitochondrial changes mediated by PDK1-4 inhibition using siRNA or PDK inhibitors in inflammatory cytokine mixture (ICM)-treated primary human RPE (hRPE) cells. PDK4 silencing only in ICM-treated hRPE cells restored mitochondrial respiration and reduced inflammatory cytokine secretion. Likewise, GM10395, a specific PDK4 inhibitor, restored oxidative phosphorylation and decreased ICM-induced upregulation of inflammatory cytokine secretion. In a laser-induced CNV mouse model, GM10395 significantly alleviated CNV. Taken together, we demonstrate that specific PDK4 inhibition could be a therapeutic strategy for neovascular AMD by preventing mitochondrial metabolic reprogramming in the RPE under inflammatory conditions.},
}
@article {pmid39121994,
year = {2025},
author = {Cicinelli, MV and Barlocci, E and Rissotto, F and Russo, A and Giuffrè, C and Introini, U and Bandello, F},
title = {The Discrepancy Between Visual Acuity Decline and Foveal Involvement in Geographic Atrophy.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {1},
pages = {31-39},
doi = {10.1016/j.oret.2024.07.025},
pmid = {39121994},
issn = {2468-6530},
mesh = {Humans ; *Visual Acuity ; Female ; Male ; *Geographic Atrophy/physiopathology/diagnosis ; *Fovea Centralis/pathology ; Retrospective Studies ; Aged ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Follow-Up Studies ; *Disease Progression ; *Fundus Oculi ; Aged, 80 and over ; },
abstract = {PURPOSE: To investigate the discrepancy between visual acuity (VA) decline and foveal involvement in geographic atrophy (GA) secondary to nonexudative age-related macular degeneration (AMD), and to explore how early retinal changes impact the progression of visual impairment.<br><br>DESIGN: Retrospective, longitudinal cohort study.<br><br>SUBJECTS: This study evaluated 80 eyes from 60 patients (mean age, 74.2 &#xb1; 10 years) with progressing non-neovascular AMD.<br><br>METHODS: Blue-light fundus autofluorescence (FAF) and spectral-domain OCT (SD-OCT) were utilized to monitor GA progression and the onset of foveal involvement. The study analyzed VA changes over an average follow-up of 60 &#xb1; 26.4 months, encompassing 785 observations. Mixed-effects models with natural splines assessed the effects of demographic and ocular characteristics on baseline VA and its rate of decline. Survival analyses compared the timing of anatomic changes with the most rapid functional declines, indicated by the highest first derivative of VA trajectories. Discrepancies between visual and anatomic changes were explored using generalized linear mixed-effects models.<br><br>MAIN OUTCOME MEASURES: Monthly VA changes, onset and impact of foveal involvement, and factors influencing baseline VA and rate of decline.<br><br>RESULTS: Visual acuity declined consistently by an average of 0.010 logarithm of the minimum angle of resolution (LogMAR) per month (standard error [SE], 0.0003; P < 0.001). The onset of foveal involvement significantly exacerbated this decline, adding an average loss of 0.15 LogMAR (SE, 0.02; P < 0.001). Stabilization of VA typically occurred around 41 months post-foveal involvement. Significant factors associated with worse baseline VA were older age, female gender, unifocal GA morphology, and drusen-associated forms of GA (P < 0.05). The most rapid declines in VA typically occurred about 9 months (interquartile range, 0-27 months) before detectable subfoveal changes. The reticular FAF pattern (27/46 [59%] vs. 2/13 [15%], P&#xa0;= 0.02) and smaller baseline GA lesions (P&#xa0;= 0.01) were associated with faster deterioration preceding visible foveal damage.<br><br>CONCLUSIONS: This study demonstrates that significant VA loss in GA can precede detectable foveal involvement, suggesting a window for early interventions to slow the progression of visual impairment. Identifying specific GA characteristics and FAF patterns as predictors of rapid VA decline supports the need for personalized treatment strategies to optimize outcomes for patients with nonexudative AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39121492,
year = {2024},
author = {Spaide, RF},
title = {PATHWAYS TO GEOGRAPHIC ATROPHY IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1655-1665},
doi = {10.1097/IAE.0000000000004242},
pmid = {39121492},
issn = {1539-2864},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; Female ; Retrospective Studies ; Male ; *Tomography, Optical Coherence/methods ; Aged, 80 and over ; *Fluorescein Angiography/methods ; Aged ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Visual Acuity ; Follow-Up Studies ; Macular Degeneration/diagnosis/complications ; Retinal Drusen/diagnosis ; Fundus Oculi ; Middle Aged ; },
abstract = {PURPOSE: To characterize and quantify the precursor lesions of geographic atrophy in eyes with age-related macular degeneration.<br><br>METHODS: A retrospective study of eyes with a minimum of 6-month follow-up before developing geographic atrophy. Evaluations included color and autofluorescence imaging, along with spectral-domain optical coherence tomography, employing definitions from the Consensus of Atrophy Meeting Group and Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.<br><br>RESULTS: There were 55 eyes of 44 patients, who had a mean age of 81.3 years at onset of atrophy; 35 (63.6%) were female. The mean duration of follow-up before and after the advent of geographic atrophy was 4.9 years and 1.2 years, respectively. Geographic atrophy was preceded by collapse of a druse in 41 eyes (74.5%). Of these, 29 (70.7%) were drusenoid pigment epithelial detachments. Among the eyes with regressing drusen, there were 9 with overlying vitelliform deposit, and all had concurrent subretinal drusenoid deposit; however, 19 of 30 eyes with no vitelliform deposit overlying the druse had concurrent subretinal drusenoid deposit, a difference that was significant (P < 0.001). Regression of subretinal drusenoid deposit was found in 4 eyes (7.3%), regression of vitelliform deposit associated with subretinal drusenoid deposit in 5 (9.1%), and regression of vitelliform deposit in eyes concurrently harboring drusen was found in 3 (5.4%) and regression of vitelliform deposit alone in 2 (3.6%) at the site of eventual development of geographic atrophy.<br><br>CONCLUSION: Geographic atrophy appears to develop from multiple pathways as manifested by the many precursor lesions, all various forms of extracellular deposit, that upon regression, result in a common end-stage appearance.},
}
@article {pmid39120913,
year = {2024},
author = {Won, J and Takahashi, H and Ploner, SB and Karbole, W and Abu-Qamar, O and Yaghy, A and Marmalidou, A and Kaiser, S and Hwang, Y and Lin, J and Witkin, A and Desai, S and Baumal, CR and Maier, A and Curcio, CA and Waheed, NK and Fujimoto, JG},
title = {Topographic Measurement of the Subretinal Pigment Epithelium Space in Normal Aging and Age-Related Macular Degeneration Using High-Resolution OCT.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {10},
pages = {18},
pmid = {39120913},
issn = {1552-5783},
support = {R01 EY011289/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; R01 EY034080/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Aged ; Middle Aged ; Prospective Studies ; Cross-Sectional Studies ; Female ; Male ; Aged, 80 and over ; *Aging/physiology ; Adult ; Young Adult ; Bruch Membrane/pathology/diagnostic imaging ; Macular Degeneration/diagnosis/physiopathology ; },
abstract = {PURPOSE: A micrometer scale hyporeflective band within the retinal pigment epithelium basal lamina - Bruch's membrane complex (RPE-BL-BrM) was topographically measured in aging and age-related macular degeneration (AMD).<br><br>METHODS: In a prospective cross-sectional study, 90 normal eyes from 76 subjects (range = 23-90 years) and 53 dry AMD eyes from 47 subjects (range = 62-91 years) were enrolled. Isotropic volume raster scans over 6&#xa0;mm &#xd7; 6&#xa0;mm (500 &#xd7; 500 A-scans) were acquired using a high-resolution (2.7 &#xb5;m axial resolution) spectral-domain optical coherence tomography (SD-OCT) prototype instrument. Six consecutive optical coherence tomography (OCT) volumes were computationally motion-corrected and fused to improve feature visibility. A boundary regression neural network was developed to measure hyporeflective band thickness. Topographic dependence was evaluated over a 6-mm-diameter Early Treatment Diabetic Retinopathy Study (ETDRS) grid.<br><br>RESULTS: The hyporeflective band thickness map (median of 4.3 &#xb5;m and 7.8 &#xb5;m in normal and AMD eyes, respectively) is thicker below and radially symmetric around the fovea. In normal eyes, age-associated differences occur within 0.7 to 2.3&#xa0;mm from the foveal center (P < 0.05). In AMD eyes, the hyporeflective band is hypothesized to be basal laminar deposits (BLamDs) and is thicker within the 3-mm ETDRS circle (P < 0.0002) compared with normal eyes. The inner ring is the most sensitive location to detect age versus AMD-associated changes within the RPE-BL-BrM. AMD eyes with subretinal drusenoid deposits (SDDs) have a significantly thicker hyporeflective band (P < 0.001) than those without SDDs.<br><br>CONCLUSIONS: The hyporeflective band is a quantifiable biomarker which differentiates AMD from aging. Longitudinal studies are warranted. The hyporeflective band may be a useful biomarker for risk stratification and disease progression.},
}
@article {pmid39120894,
year = {2024},
author = {Liu, A and Anderson, KE and Levy, J and Johnson, TV and Polsky, D and Anderson, G},
title = {Macular Degeneration Drug Prescribing Patterns After Step Therapy Introduction in Medicare Advantage.},
journal = {JAMA health forum},
volume = {5},
number = {8},
pages = {e242446},
pmid = {39120894},
issn = {2689-0186},
mesh = {Humans ; *Medicare Part C ; United States ; Retrospective Studies ; Aged ; Male ; Female ; *Macular Degeneration/drug therapy ; *Bevacizumab/therapeutic use/administration &amp; dosage ; *Practice Patterns, Physicians'/statistics &amp; numerical data ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Aged, 80 and over ; Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; },
abstract = {IMPORTANCE: In Medicare Advantage (MA), step therapy for physician-administered drugs is an approach to lowering drug spending. The impact of step therapy in MA on prescribing behavior and the magnitude of any changes has not been analyzed.<br><br>OBJECTIVE: To evaluate the impact of step therapy on macular degeneration drug prescribing patterns for 3 large MA insurers.<br><br>This was a retrospective encounter-based analysis using 20% nationally representative MA outpatient and carrier encounter records for 2017 to 2019. Participants were MA beneficiaries who were 65 years or older and had received a macular degeneration drug administration. Macular degeneration drug administrations for beneficiaries of MA Aetna, Humana, and UnitedHealthcare (UHC) insurers were assessed. Humana implemented macular degeneration step therapy in 2019, setting bevacizumab as the plan-preferred drug, and aflibercept and ranibizumab as the plan-nonpreferred drugs. Aetna and UHC, which did not implement macular degeneration step therapy, served as the control group. Data analyses were performed from May 2024 to December 2024.<br><br>EXPOSURES: A macular degeneration drug administration subject to a step therapy policy.<br><br>MAIN OUTCOME AND MEASURES: A binary indicator of whether the drug administered was bevacizumab. Linear probability models and a difference-in-differences framework were used to quantify changes in prescribing patterns before and after the introduction of step therapy for MA insurers that did and did not implement step therapy. To empirically measure the impact of step therapy, the first administration of a treatment episode was assessed, followed by switching patterns.<br><br>RESULTS: A total of 18&#x202f;331 MA beneficiaries, 21&#x202f;683 treatment episodes, and 171&#x202f;985 drug administrations were included across the control and treatment groups. The difference-in-differences regressions found a 7.8% (95% CI, 4.9%-10.7%; P&#x2009;<&#x2009;.001) greater probability of being prescribed bevacizumab for the first administration due to step therapy. The predicted probabilities of preferred-drug administration in the treatment group increased from 0.61 to 0.70 between the periods before and after step therapy implementation for the first administration. Step therapy was not significantly associated with an increased rate of medication switching (hazard ratio, 0.86; 95% CI, 0.71-1.06; P&#x2009;=&#x2009;.15).<br><br>CONCLUSIONS AND RELEVANCE: The findings of this retrospective encounter-based analysis indicate that step therapy is associated with a greater probability of prescribing the plan-preferred drug for the first administration. The analysis failed to find a statistically significant greater rate of medication switching within a treatment episode. Step therapy changed macular degeneration prescribing patterns, but step therapy alone did not transition all administrations to the plan-preferred drug.},
}
@article {pmid39119460,
year = {2024},
author = {Xu, B and Hu, Y and Di, J and Liu, Z and Yu, Z and Han, L and Ning, Y},
title = {The negative association between the docosapentaenoic acid intake and the incidence of AMD based on NHANES 2005-2008.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1435775},
pmid = {39119460},
issn = {2296-861X},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is an ophthalmic disease that causes visual impairment and is one of the leading causes of blindness in the elderly. Fatty acids are essential nutrients required by the body and play a cornerstone role in the life activities of the body. Many studies have reported that fatty acids are involved in the development of AMD. To confirm this association, we conducted the present study.<br><br>METHODS: We analyzed the association between all fatty acid intake and AMD using National Health and Nutrition Examination Survey (NHANES) data from 2005-2008. Quantile regression was performed to assess the effect of fatty acids on AMD at different intake levels.<br><br>RESULTS: After adjusting for covariates, only saturated fatty acids showed no significant difference between AMD patients and non-AMD patients (23.64 g vs. 26.03 g, p = 0.052). Total fat (70.88 g vs. 78.86 g, p = 0.024), monounsaturated fatty acids (25.87 g vs. 28.95 g, p = 0.019), polyunsaturated fatty acids (15.10 g vs. 17.07 g, p = 0.017) showed significant differences between the two groups. When AMD was considered as an outcome, the association between AMD and docosaentaenoic acid (DPA) was negative in the multivariate logic model (model 1: OR = <0.001, 95% CI = <0.001 ~ 0.734; model 2: OR = <0.001, 95% CI = <0.001 ~ 0.002; model 3: OR = <0.001, 95% CI = <0.001 ~ 0.002). In the quantile regression, DPA was shown to be negatively associated with the presence of AMD only in the fourth quartile in model 2 and model 3 (model 2: OR = <0.001, 95% CI = <0.001 ~ 0.927; model 3: OR = <0.001, 95% CI = <0.001 ~ 0.775).<br><br>DISCUSSION: Therefore, based on above results, we concluded that DPA intake could prevent the development of AMD.},
}
@article {pmid39117703,
year = {2024},
author = {Neelam, K and Ng, SMS and Ho, EL and Au Eong, KG},
title = {Lacquer cracks in pathological myopia: a clinical review.},
journal = {Eye (London, England)},
volume = {38},
number = {15},
pages = {2859-2873},
pmid = {39117703},
issn = {1476-5454},
mesh = {Humans ; *Myopia, Degenerative/complications/diagnosis ; *Bruch Membrane/pathology ; Tomography, Optical Coherence ; },
abstract = {Lacquer cracks, described as breaks in the Bruch's membrane, are unique lesions in the spectrum of fundus changes associated with pathological myopia. Lacquer cracks are generally believed to be relatively innocuous lesions by themselves; however, progression to other features of myopic macular degeneration, such as patchy chorioretinal atrophy and choroidal neovascularization, may result in irreversible visual impairment. With the rising prevalence of pathological myopia to epidemic proportions, particularly in the Asian countries, ophthalmologists expect to encounter lacquer cracks more frequently in clinical practice. Therefore, it is crucial for the ophthalmic community to be aware of lacquer cracks and to actively look for these lesions in myopic patients so that early detection and close monitoring can help prevent blinding complications. This article provides a comprehensive review on lacquer cracks in eyes with pathological myopia from a clinical perspective.},
}
@article {pmid39116948,
year = {2025},
author = {Alsoudi, AF and Koo, E and Wai, K and Mruthyunjaya, P and Rahimy, E},
title = {Ocular Neovascular Conversion and Systemic Bleeding Complications in Patients with Age-Related Macular Degeneration on Anticoagulants.},
journal = {Ophthalmology},
volume = {132},
number = {2},
pages = {219-227},
doi = {10.1016/j.ophtha.2024.07.034},
pmid = {39116948},
issn = {1549-4713},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Anticoagulants/adverse effects/therapeutic use ; Aged ; *Warfarin/adverse effects ; *Wet Macular Degeneration/diagnosis/chemically induced ; *Vitreous Hemorrhage/diagnosis/chemically induced ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Propensity Score ; Intravitreal Injections ; Atrial Fibrillation/drug therapy ; Follow-Up Studies ; Risk Factors ; Visual Acuity ; Administration, Oral ; Vitrectomy ; *Choroidal Neovascularization/diagnosis ; Middle Aged ; Retinal Hemorrhage ; },
abstract = {PURPOSE: Conversion to neovascular disease in patients with non-neovascular age-related macular degeneration (AMD) initiated on direct oral anticoagulants (DOACs) compared with matched patients treated with warfarin.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: The study included 20 300 patients and 13 387 patients with non-neovascular AMD initiated on DOACs or warfarin, respectively, before propensity score matching (PSM).<br><br>METHODS: TriNetX was used to identify patients diagnosed with non-neovascular AMD stratified by treatment with DOACs or warfarin with at least 6 months of follow-up. Propensity score matching was performed to control for baseline demographics and medical comorbidities.<br><br>MAIN OUTCOME MEASURES: Relative risk (RR) of developing neovascular AMD, macular hemorrhage (MH), vitreous hemorrhage (VH), and requiring an ocular intervention (intravitreal anti-VEGF therapy or pars plana vitrectomy [PPV]) within 6 months and 1 year. Patients with chronic atrial fibrillation (AF) on anticoagulation were separately evaluated for the same measures within 5 years after initiating therapy.<br><br>RESULTS: Treatment with warfarin was associated with a higher risk of developing neovascular AMD at 6 months (RR, 1.24, 95% confidence interval [CI], 1.12-1.39; P < 0.001) and 1 year (RR, 1.26, 95% CI, 1.14-1.40; P < 0.001) when compared with matched patients treated with DOACs. There was an increased risk of requiring intravitreal anti-VEGF therapy (6 months: RR, 1.30; 95% CI, 1.13-1.49; P < 0.001; 1 year: RR, 1.31, 95% CI, 0.72-2.05; P < 0.001) and PPV (6 months: RR, 2.13; 95% CI, 1.16-3.94; P&#x2009;=&#x2009;0.01; 1 year: RR, 2.29, 95% CI, 1.30-4.05; P&#xa0;= 0.003). Among patients with AMD and AF treated with warfarin, there was an increased risk of ocular complications (neovascular AMD: RR, 1.25; 95% CI, 1.14-1.38; P < 0.001; MH: RR, 1.86; 95% CI, 1.47-2.35; P < 0.001; VH: RR, 2.22; 95% CI, 1.51-3.26; P < 0.001) and need for intravitreal anti-VEGF therapy (RR, 1.34; 95% CI, 1.18-1.52; P < 0.001) over an extended 5-year period. There was no significant difference in the development of major systemic hemorrhagic events between the 2 cohorts over 5 years.<br><br>CONCLUSIONS: Patients with non-neovascular AMD treated with warfarin were more likely to develop neovascular disease and require ocular intervention for hemorrhagic complications when compared with matched patients initiated on DOACs.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39116541,
year = {2024},
author = {Bousquet, E and Abraham, N and Estawro, R and Khadka, S and Voichanski, S and Mafi, M and Au, A and Santina, A and Sadda, S and Sarraf, D},
title = {SUB RETINAL PIGMENT EPITHELIUM HYPOREFLECTIVE SPACES PRECEDING LARGE DRUSEN COLLAPSE.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {12},
pages = {2041-2048},
doi = {10.1097/IAE.0000000000004233},
pmid = {39116541},
issn = {1539-2864},
support = {//Research to Prevent Blindness/ ; },
mesh = {Humans ; Female ; Retrospective Studies ; *Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; *Retinal Drusen/etiology/diagnosis/pathology ; Aged ; Male ; Visual Acuity/physiology ; Aged, 80 and over ; Fluorescein Angiography/methods ; *Retinal Detachment/diagnosis/etiology ; Disease Progression ; Middle Aged ; },
abstract = {PURPOSE: To describe and study hyporeflective subretinal pigment epithelium (RPE) spaces in large drusen and drusenoid pigment epithelial detachment before collapse.<br><br>METHOD: Retrospective longitudinal study enrolled patients with large and very large drusen caused by intermediate age-related macular degeneration. The following optical coherence tomography parameters were assessed: drusen size (maximum width and height), optical coherence tomography biomarkers of RPE atrophy, presence of intraretinal and subretinal fluid, acquired vitelliform lesion, and sub-RPE regions of hyporeflectivity within the pigment epithelial detachment compartment.<br><br>RESULTS: Of the 50 eyes from 41 patients (mean age 77.1 &#xb1; 9 years, 78% women) with large and very large drusen, 16 eyes progressed to collapse. Eyes with sub-RPE hyporeflective spaces (n = 8 eyes, 50%) were associated with greater drusen width and height than those without sub-RPE hyporeflective spaces. At the collapse visit, eyes with sub-RPE hyporeflective spaces displayed poorer visual acuity and greater incomplete RPE and outer retinal atrophy and complete RPE and outer retinal atrophy length than eyes without sub-RPE hyporeflective spaces (P = 0.004 and P = 0.04, respectively).<br><br>CONCLUSION: Sub-RPE hyporeflective spaces are a novel optical coherence tomography finding of large and very large drusen that collapse to atrophy. Progressive RPE dysfunction and failure may lead to reduced drusenoid material formation and progressive degenerative hydration of the large drusen before collapse, but this awaits confirmation with histopathological analysis.},
}
@article {pmid39115837,
year = {2024},
author = {Gao, M and Zhou, J and Zhao, J and Liu, Z and Luo, X and Yang, C and Yu, X and Tang, M and Zhu, J and Yan, X},
title = {Genetic Influence of Oily Fish Intake on Age-Related Macular Degeneration Risk: A Two-Sample Mendelian Randomization Analysis.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {8},
pages = {14},
pmid = {39115837},
issn = {2164-2591},
mesh = {*Mendelian Randomization Analysis/methods ; *Macular Degeneration/genetics/epidemiology/etiology ; Humans ; *Genome-Wide Association Study ; *Fish Oils/administration &amp; dosage ; Risk Factors ; Polymorphism, Single Nucleotide ; Animals ; Genetic Predisposition to Disease ; Fishes/genetics ; Finland/epidemiology ; },
abstract = {PURPOSE: Emerging research indicates a link between the intake of fatty fish and age-related macular degeneration (AMD). However, observational studies fall short in establishing a direct causal link between oily fish intake and AMD. We wanted to determine whether causal association lies between oily fish intake and age-related macular degeneration (AMD) risk in human beings.<br><br>METHODS: This two-sample mendelian randomization (MR) study used the MR method to probe the genetic causality in the relationship between oily fish intake and AMD. The genome-wide association study (GWAS) data for AMD were acquired from a Finnish database, whereas the data on fish oil intake came from the UK Biobank. The analysis used several approaches such as inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode MR. In addition, the Cochran's Q test was used to evaluate heterogeneity in the MR data. The MR-Egger intercept and MR-pleiotropy residual sum and outlier (MR-PRESSO) tests were used to assess the presence of horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted to determine the reliability of the association.<br><br>RESULTS: The IVW method revealed that the intake of oily fish is an independent risk factor for AMD (P = 0.034). It also suggested a minimal likelihood of horizontal pleiotropy affecting the causality (P > 0.05), with no substantial heterogeneity detected in the genetic variants (P > 0.05). The leave-one-out analysis confirmed the reliability and stability of this correlation.<br><br>CONCLUSIONS: This research used a two-sample MR analysis to provide evidence of a genetic causal relationship between the eating of oily fish and AMD. This discovery held potential significance in AMD prevention.},
}
@article {pmid39114980,
year = {2024},
author = {DiCesare, SM and Ortega, AJ and Collier, GE and Daniel, S and Thompson, KN and McCoy, MK and Posner, BA and Hulleman, JD},
title = {GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.},
journal = {JCI insight},
volume = {9},
number = {15},
pages = {},
pmid = {39114980},
issn = {2379-3708},
support = {P30 EY030413/EY/NEI NIH HHS/United States ; R01 EY027785/EY/NEI NIH HHS/United States ; R21 EY019817/EY/NEI NIH HHS/United States ; S10 OD026758/OD/NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; *Macular Degeneration/pathology/genetics/drug therapy/metabolism ; Humans ; *Extracellular Matrix Proteins/metabolism/genetics ; *Extracellular Matrix/metabolism/drug effects ; Pyridines/pharmacology ; Pyrimidines/pharmacology ; Glycogen Synthase Kinase 3/metabolism/antagonists &amp; inhibitors/genetics ; Disease Models, Animal ; Retinal Dystrophies/metabolism/pathology/genetics ; Optic Disk Drusen/congenital ; },
abstract = {Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) is an age-related macular degeneration-like (AMD-like) retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3). To identify new small molecules that reduce F3 production in retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus that enabled simple, sensitive, and high-throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE and non-RPE cells. Low-level, long-term CHIR treatment promoted remodeling of the RPE extracellular matrix, reducing sub-RPE deposit-associated proteins (e.g., amelotin, complement component 3, collagen IV, and fibronectin), while increasing RPE differentiation factors (e.g., tyrosinase, and pigment epithelium-derived factor). In vivo, treatment of 8-month-old R345W+/+ knockin mice with CHIR (25 mg/kg i.p., 1 mo) was well tolerated and significantly reduced R345W F3-associated AMD-like basal laminar deposit number and size, thereby preventing the main pathological feature in these mice. This is an important demonstration of small molecule-based prevention of AMD-like pathology in ML/DHRD mice and may herald a rejuvenation of interest in GSK3 inhibition for the treatment of retinal degenerative diseases, including potentially AMD itself.},
}
@article {pmid39114482,
year = {2024},
author = {Wagner, N and Tsai, T and Reinehr, S and Theile, J and Dick, HB and Joachim, SC},
title = {Retinal debris triggers cytotoxic damage in cocultivated primary porcine RPE cells.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1401571},
pmid = {39114482},
issn = {1662-4548},
abstract = {INTRODUCTION: One of the most common causes of vision loss in the elderly population worldwide is age-related macular degeneration (AMD). Subsequently, the number of people affected by AMD is estimated to reach approximately 288 million by the year 2040. The aim of this study was to develop an ex vivo model that simulates various aspects of the complex AMD pathogenesis.<br><br>METHODS: For this purpose, primary porcine retinal pigment epithelial cells (ppRPE) were isolated and cultured. One group was exposed to medium containing sodium iodate (NaIO3) to induce degeneration. The others were exposed to different supplemented media, such as bovine serum albumin (BSA), homogenized porcine retinas (HPR), or rod outer segments (ROOS) for eight days to promote retinal deposits. Then, these ppRPE cells were cocultured with porcine neuroretina explants for another eight days. To assess the viability of ppRPE cells, live/dead assay was performed at the end of the study. The positive RPE65 and ZO1 area was evaluated by immunocytochemistry and the expression of RLBP1, RPE65, and TJP1 was analyzed by RT-qPCR. Additionally, drusen (APOE), inflammation (ITGAM, IL6, IL8, NLRP3, TNF), oxidative stress (NFE2L2, SOD1, SOD2), and hypoxia (HIF1A) markers were investigated. The concentration of the inflammatory cytokines IL-6 and IL-8 was determined in medium supernatants from day 16 and 24 via ELISA.<br><br>RESULTS: Live/dead assay suggests that especially exposure to NaIO3 and HPR induced damage to ppRPE cells, leading in a significant ppRPE cell loss. All supplemented media resulted in decreased RPE-characteristic markers (RPE65; ZO-1) and gene expression like RLBP1 and RPE65 in the cultured ppRPE cells. Besides, some inflammatory, oxidative as well as hypoxic stress markers were altered in ppRPE cells cultivated with NaIO3. The application of HPR induced an enhanced APOE expression. Pre-exposure of the ppRPE cells led to a diminished number of cones in all supplemented media groups compared to controls.<br><br>DISCUSSION: Overall, this novel coculture model represents an interesting initial approach to incorporating deposits into coculture to mimic AMD pathogenesis. Nevertheless, the effects of the media used need to be investigated in further studies.},
}
@article {pmid39113560,
year = {2024},
author = {Di Rienzo, M and Romagnoli, A and Refolo, G and Vescovo, T and Ciccosanti, F and Zuchegna, C and Lozzi, F and Occhigrossi, L and Piacentini, M and Fimia, GM},
title = {Role of AMBRA1 in mitophagy regulation: emerging evidence in aging-related diseases.},
journal = {Autophagy},
volume = {20},
number = {12},
pages = {2602-2615},
pmid = {39113560},
issn = {1554-8635},
mesh = {Animals ; Humans ; *Adaptor Proteins, Signal Transducing/metabolism ; *Aging/metabolism ; Autophagy ; Mitochondria/metabolism ; *Mitophagy ; },
abstract = {Aging is a gradual and irreversible physiological process that significantly increases the risks of developing a variety of pathologies, including neurodegenerative, cardiovascular, metabolic, musculoskeletal, and immune system diseases. Mitochondria are the energy-producing organelles, and their proper functioning is crucial for overall cellular health. Over time, mitochondrial function declines causing an increased release of harmful reactive oxygen species (ROS) and DNA, which leads to oxidative stress, inflammation and cellular damage, common features associated with various age-related pathologies. The impairment of mitophagy, the selective removal of damaged or dysfunctional mitochondria by autophagy, is relevant to the development and progression of age-related diseases. The molecular mechanisms that regulates mitophagy levels in aging remain largely uncharacterized. AMBRA1 is an intrinsically disordered scaffold protein with a unique property of regulating the activity of both proliferation and autophagy core machineries. While the role of AMBRA1 during embryonic development and neoplastic transformation has been extensively investigated, its functions in post-mitotic cells of adult tissues have been limited due to the embryonic lethality caused by AMBRA1 deficiency. Recently, a key role of AMBRA1 in selectively regulating mitophagy in post-mitotic cells has emerged. Here we summarize and discuss these results with the aim of providing a comprehensive view of the mitochondrial roles of AMBRA1, and how defective activity of AMBRA1 has been functionally linked to mitophagy alterations observed in age-related degenerative disorders, including muscular dystrophy/sarcopenia, Parkinson diseases, Alzheimer diseases and age-related macular degeneration.Abbreviations: AD: Alzheimer disease; AMD: age-related macular degeneration; AMBRA1: autophagy and beclin 1 regulator 1; APOE4: apolipoprotein E4; ATAD3A: ATPase family AAA domain containing 3A; ATG: autophagy related; BCL2: BCL2 apoptosis regulator; BH3: BCL2-homology-3; BNIP3L/NIX: BCL2 interacting protein 3 like; CDK: cyclin dependent kinase; CHUK/IKKα: component of inhibitor of nuclear factor kappa B kinase complex; CRL2: CUL2-RING ubiquitin ligase; DDB1: damage specific DNA binding protein 1; ER: endoplasmic reticulum; FOXO: forkhead box O; FUNDC1: FUN14 domain containing 1; GBA/β-glucocerebrosidase: glucosylceramidase beta; HUWE1: HECT, UBA and WWE domain containing E3 ubiquitin protein ligase 1; IDR: intrinsically disordered region; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAVS: mitochondrial antiviral signaling protein; MCL1: MCL1 apoptosis regulator, BCL2 family member; MFN2: mitofusin 2; MTOR: mechanistic target of rapamycin kinase; MSA: multiple system atrophy; MYC: MYC proto-oncogene, bHLH transcription factor; NUMA1: nuclear mitotic apparatus protein 1; OMM; mitochondria outer membrane; PD: Parkinson disease; PHB2: prohibitin 2; PINK1: PTEN induced kinase 1; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PTK2/FAK: protein tyrosine kinase 2; ROS: reactive oxygen species; RPE: retinal pigment epithelium; SAD: sporadic AD; SOCS3: suppressor of cytokine signaling 3; SRC, SRC proto-oncogene, non-receptor tyrosine kinase; STAT3: signal transducer and activator of transcription 3; STING1: stimulator of interferon response cGAMP interactor 1; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; TGFB/TGFβ: transforming growth factor beta; TOMM: translocase of outer mitochondrial membrane; TRAF6: TNF receptor associated factor 6; TRIM32: tripartite motif containing 32; ULK1: unc-51 like autophagy activating kinase 1.},
}
@article {pmid39111520,
year = {2024},
author = {Tran, L and Kandel, H and Sari, D and Chiu, CH and Watson, SL},
title = {Artificial Intelligence and Ophthalmic Clinical Registries.},
journal = {American journal of ophthalmology},
volume = {268},
number = {},
pages = {263-274},
doi = {10.1016/j.ajo.2024.07.039},
pmid = {39111520},
issn = {1879-1891},
mesh = {Humans ; *Artificial Intelligence ; *Registries ; *Ophthalmology/organization &amp; administration ; Eye Diseases ; Algorithms ; Machine Learning ; },
abstract = {PURPOSE: The recent advances in artificial intelligence (AI) represent a promising solution to increasing clinical demand and ever limited health resources. Whilst powerful, AI models require vast amounts of representative training data to output meaningful predictions in the clinical environment. Clinical registries represent a promising source of large volume real-world data which could be used to train more accurate and widely applicable AI models. This review aims to provide an overview of the current applications of AI to ophthalmic clinical registry data.<br><br>DESIGN AND METHODS: A systematic search of EMBASE, Medline, PubMed, Scopus and Web of Science for primary research articles that applied AI to ophthalmic clinical registry data was conducted in July 2024.<br><br>RESULTS: Twenty-three primary research articles applying AI to ophthalmic clinic registries (n = 14) were found. Registries were primarily defined by the condition captured and the most common conditions where AI was applied were glaucoma (n = 3) and neovascular age-related macular degeneration (n = 3). Tabular clinical data was the most common form of input into AI algorithms and outputs were primarily classifiers (n = 8, 40%) and risk quantifier models (n = 7, 35%). The AI algorithms applied were almost exclusively supervised conventional machine learning models (n = 39, 85%) such as decision tree classifiers and logistic regression, with only 7 applications of deep learning or natural language processing algorithms. Significant heterogeneity was found with regards to model validation methodology and measures of performance.<br><br>CONCLUSIONS: Limited applications of deep learning algorithms to clinical registry data have been reported. The lack of standardized validation methodology and heterogeneity of performance outcome reporting suggests that the application of AI to clinical registries is still in its infancy constrained by the poor accessibility of registry data and reflecting the need for a standardization of methodology and greater involvement of domain experts in the future development of clinically deployable AI.},
}
@article {pmid39111407,
year = {2024},
author = {Kim, SY and Cheon, J},
title = {Senescence-associated microvascular endothelial dysfunction: A focus on the blood-brain and blood-retinal barriers.},
journal = {Ageing research reviews},
volume = {100},
number = {},
pages = {102446},
doi = {10.1016/j.arr.2024.102446},
pmid = {39111407},
issn = {1872-9649},
mesh = {Humans ; *Blood-Brain Barrier/physiopathology/metabolism/pathology ; *Blood-Retinal Barrier/physiology/metabolism ; *Aging/physiology/pathology ; Animals ; *Endothelium, Vascular/physiopathology/metabolism ; Cellular Senescence/physiology ; Neurodegenerative Diseases/physiopathology/metabolism/pathology ; },
abstract = {The blood-brain barrier (BBB) and blood-retinal barrier (BRB) constitute critical physiochemical interfaces, precisely orchestrating the bidirectional communication between the brain/retina and blood. Increased permeability or leakage of these barriers has been demonstrably linked to age-related vascular and parenchymal damage. While it has been suggested that the gradual aging process may coincide with disruptions in these barriers, this phenomenon is significantly exacerbated in individuals with age-related neurodegenerative disorders (ARND). This review focuses on the microvascular endothelium, a key constituent of BBB and BRB, highlighting the impact of endothelial senescence on barrier dysfunction and exploring recent discoveries regarding core pathways implicated in its breakdown. Subsequently, we address the "vascular senescence hypothesis" for ARND, with a particular emphasis on Alzheimer's disease and age-related macular degeneration, centered on endothelial senescence. Finally, we discuss potential senotherapeutic strategies targeting barrier dysfunction.},
}
@article {pmid39109978,
year = {2024},
author = {Katari, V and Dalal, K and Adapala, RK and Guarino, BD and Kondapalli, N and Paruchuri, S and Thodeti, CK},
title = {A TRP to Pathological Angiogenesis and Vascular Normalization.},
journal = {Comprehensive Physiology},
volume = {14},
number = {2},
pages = {5389-5406},
pmid = {39109978},
issn = {2040-4603},
support = {R15 CA202847/CA/NCI NIH HHS/United States ; T32 HL134625/HL/NHLBI NIH HHS/United States ; R25 HL088992/HL/NHLBI NIH HHS/United States ; R01 AI144115/AI/NIAID NIH HHS/United States ; R01 HL148585/HL/NHLBI NIH HHS/United States ; R01 HL119705/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Animals ; *Neovascularization, Pathologic ; Transient Receptor Potential Channels/metabolism/physiology ; Signal Transduction ; },
abstract = {Uncontrolled angiogenesis underlies various pathological conditions such as cancer, age-related macular degeneration (AMD), and proliferative diabetic retinopathy (PDR). Hence, targeting pathological angiogenesis has become a promising strategy for the treatment of cancer and neovascular ocular diseases. However, current pharmacological treatments that target VEGF signaling have met with limited success either due to acquiring resistance against anti-VEGF therapies with serious side effects including nephrotoxicity and cardiovascular-related adverse effects in cancer patients or retinal vasculitis and intraocular inflammation after intravitreal injection in patients with AMD or PDR. Therefore, there is an urgent need to develop novel strategies which can control multiple aspects of the pathological microenvironment and regulate the process of abnormal angiogenesis. To this end, vascular normalization has been proposed as an alternative for antiangiogenesis approach; however, these strategies still focus on targeting VEGF or FGF or PDGF which has shown adverse effects. In addition to these growth factors, calcium has been recently implicated as an important modulator of tumor angiogenesis. This article provides an overview on the role of major calcium channels in endothelium, TRP channels, with a special focus on TRPV4 and its downstream signaling pathways in the regulation of pathological angiogenesis and vascular normalization. We also highlight recent findings on the modulation of TRPV4 activity and endothelial phenotypic transformation by tumor microenvironment through Rho/YAP/VEGFR2 mechanotranscriptional pathways. Finally, we provide perspective on endothelial TRPV4 as a novel VEGF alternative therapeutic target for vascular normalization and improved therapy. © 2024 American Physiological Society. Compr Physiol 14:5389-5406, 2024.},
}
@article {pmid39107525,
year = {2024},
author = {Zhang, S and Yang, Y and Chen, J and Su, S and Cai, Y and Yang, X and Sang, A},
title = {Integrating Multi-omics to Identify Age-Related Macular Degeneration Subtypes and Biomarkers.},
journal = {Journal of molecular neuroscience : MN},
volume = {74},
number = {3},
pages = {74},
pmid = {39107525},
issn = {1559-1166},
support = {NO.134422631103//Jiangsu graduate Practice and Innovation program/ ; },
mesh = {Humans ; *Macular Degeneration/genetics/metabolism ; *Transcriptome ; *Biomarkers/metabolism ; Machine Learning ; Single-Cell Analysis/methods ; Mitochondria/genetics/metabolism ; Multiomics ; },
abstract = {Age-related macular degeneration (AMD) is one of the most common causes of irreversible vision loss in the elderly. Its pathogenesis is likely multifactorial, involving a complex interaction of metabolic and environmental factors, and remains poorly understood. Previous studies have shown that mitochondrial dysfunction and oxidative stress play a crucial role in the development of AMD. Oxidative damage to the retinal pigment epithelium (RPE) has been identified as one of the major mediators in the pathogenesis of age-related macular degeneration (AMD). Therefore, this article combines transcriptome sequencing (RNA-seq) and single-cell sequencing (scRNA-seq) data to explore the role of mitochondria-related genes (MRGs) in AMD. Firstly, differential expression analysis was performed on the raw RNA-seq data. The intersection of differentially expressed genes (DEGs) and MRGs was performed. This paper proposes a deep subspace nonnegative matrix factorization (DS-NMF) algorithm to perform a multi-layer nonlinear transformation on the intersection of gene expression profiles corresponding to AMD samples. The age of AMD patients is used as prior information at the network's top level to change the data distribution. The classification is based on reconstructed data with altered distribution. The types obtained significantly differ in scores of multiple immune-related pathways and immune cell infiltration abundance. Secondly, an optimal AMD diagnosis model was constructed using multiple machine learning algorithms for external and qRT-PCR verification. Finally, ten potential therapeutic drugs for AMD were identified based on cMAP analysis. The AMD subtypes identified in this article and the diagnostic model constructed can provide a reference for treating AMD and discovering new drug targets.},
}
@article {pmid39107259,
year = {2024},
author = {McLean, A and Zhang, W and Cooke, A and Potter, NS and Kopelman, R and Paulus, YM},
title = {Targeted 8-arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model.},
journal = {ACS applied bio materials},
volume = {7},
number = {8},
pages = {5496-5505},
pmid = {39107259},
issn = {2576-6422},
support = {P30 EY007003/EY/NEI NIH HHS/United States ; R01 EY033000/EY/NEI NIH HHS/United States ; R01 EY034325/EY/NEI NIH HHS/United States ; F31 EY007003/EY/NEI NIH HHS/United States ; },
mesh = {*Choroidal Neovascularization/drug therapy/pathology/metabolism ; Animals ; *Polyethylene Glycols/chemistry ; Mice ; *Macular Degeneration/drug therapy/pathology ; *Particle Size ; *Nanoparticles/chemistry ; Disease Models, Animal ; Materials Testing ; Biocompatible Materials/chemistry/pharmacology ; Humans ; Oligopeptides/chemistry ; Mice, Inbred C57BL ; },
abstract = {8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (<10 nm), ease-of-conjugation (many functionalized variants are readily available with "click-like" properties), biocompatibility, and optical inactivity. This study evaluates 8-arm PEG uptake into cells (in vitro) and localization and clearance in vasculature (in vivo) for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting. In vitro studies show that RGD-conjugated 8-arm PEG nanoparticles exhibit enhanced cellular uptake relative to non-RGD-conjugated control NPs at 34% ± 9%. Laser-induced choroidal neovascularization (CNV) was performed in a mouse model to measure 8-arm PEG localization and clearance to model macular degeneration lesions in vivo. It was determined that both RGD-conjugated and non-RGD-conjugated (nRGD) 8-arm PEG particles localized to CNV lesions, with a half-life around 24 h. In vivo experiments showed that RGD-conjugated nanoparticles exhibited enhanced localization by 15-20% relative to without RGD controls. Exhibiting a high rate of localization and fast clearance relative to larger nanoparticles, targeted 8-arm PEG nanoparticles with a conjugated RGD-peptide could be a promising modality for macular degeneration diagnosis and therapy.},
}
@article {pmid39106031,
year = {2024},
author = {Li, T and Berdunov, V and Hamilton, R and Rojas, YG and Bührer, C and Cox, O and Postema, R and Bagijn, M},
title = {Economic Assessment in Resource-Constrained Systems: Individual-Level Simulation Model in Wet Age-Related Macular Degeneration and Diabetic Macular Oedema.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {10},
pages = {2577-2597},
pmid = {39106031},
issn = {2193-8245},
abstract = {INTRODUCTION: Cost-effectiveness analyses typically ignore healthcare system resource constraints. Ophthalmology is affected by resource constraints because of increasing disease prevalence and the use of resource-intensive treatments. This study evaluated the impact of resource constraints on the cost-effectiveness of faricimab 6 mg, compared with aflibercept 2 mg and ranibizumab biosimilar 0.5 mg, for treating wet age-related macular degeneration (wAMD) or diabetic macular oedema (DMO) over a 5-year horizon.<br><br>METHODS: A microsimulation model estimated the impact of resource constraints on patients visits, delays, costs and quality-adjusted life-year (QALY) losses due to treatment delays at a typical UK National Health Service eye hospital treating 1500 patients with wAMD and 500 patients with DMO. Patient characteristics, treatment regimens and treatment intervals were informed using published literature and expert opinion. Resource constraint was represented by limiting the number of available intravitreal injection appointments per week, with growing demand caused by rising disease prevalence. The model compared outcomes across three scenarios; each scenario involved treating all patients with one of the three treatments.<br><br>RESULTS: Over 5&#xa0;years, in a resource-constrained hospital, compared with aflibercept, faricimab use resulted in the avoidance of 12,596 delays, saved GBP/&#xa3;15,108,609 in cost and avoided the loss of 60.06 QALYs. Compared with ranibizumab biosimilar, faricimab use resulted in the avoidance of 18,910 delays, incurred &#xa3;2,069,088 extra cost and avoided the loss of 105.70 QALYs, resulting in an incremental cost-effectiveness ratio of &#xa3;19,574/QALY.<br><br>CONCLUSIONS: Accounting for resource constraints in health economic evaluation is crucial. Emerging therapies that are more durable and require less frequent clinic visits can reduce treatment delays, leading to improved QALY outcomes and reduced burden on healthcare systems. Faricimab reduced the number of delayed injections, leading to improved QALY outcomes for patients in a healthcare system with resource constraints. Faricimab is cost-saving when compared with aflibercept and cost-effective when compared with ranibizumab biosimilar.},
}
@article {pmid39104873,
year = {2024},
author = {Peiretti, E and Ascardi, C and Bandello, F and Boscia, F and Varano, M and Bartezaghi, M and De Santi, L and Staurenghi, G},
title = {Italian Patient Satisfaction with wAMD Management: SWAN Study Results.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {2183-2191},
pmid = {39104873},
issn = {1177-5467},
abstract = {PURPOSE: Limited data is available on treatment satisfaction with the management of wet age-related macular degeneration (wAMD) among patients in Italy. In this cross-sectional real-world study, treatment satisfaction with anti-vascular endothelial growth factor (anti-VEGFs) was assessed in patients with wAMD in Italy.<br><br>PATIENTS AND METHODS: This was a non-interventional, cross-sectional survey involving patients with wAMD receiving anti-VEGFs. The survey was administered through a virtual assistant via phone. Patients' treatment satisfaction was assessed using a newly developed Novartis Tailored Treatment Satisfaction Questionnaire (NVS TTSQ) and the validated Macular Disease Treatment Satisfaction Questionnaire (MacTSQ).<br><br>RESULTS: Overall, 154 evaluable patients were enrolled in 5 centers across Italy. The mean (SD) age of the patients was 76.8 years (7.01). Overall treatment satisfaction score assessed by NVS TTSQ was 40.50 (7.11), with a mean of 9.97 (1.84) on the information domain and 22.98 (4.57) on the unmet need domain. Patients were satisfied with diagnosis communication (4.99 [1.30]), information provided on treatment administration (4.58 [1.49], range 0-6), the waiting room (4.40 [1.43]), and management of visits and injections at the center (5.14 [1.12]), general management of maculopathy at the center (5.22 [1.01]). Patients were not satisfied with their independence in terms of disease management (2.56 [2.45]); they would like additional information about the disease (5.38 [1.03]) and to discuss the injection procedures (4.02 [1.94]) with already-treated patients. The overall treatment satisfaction score on MacTSQ scale was 55.84 (10.13).<br><br>CONCLUSION: Patients with wAMD are satisfied with the overall management of their disease in Italy. However, patients would like to have more information on prognosis and management of the disease.},
}
@article {pmid39104531,
year = {2024},
author = {Ahmed, CM and Johnson, HM and Lewin, AS},
title = {Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1416181},
pmid = {39104531},
issn = {1664-3224},
support = {R01 AI056152/AI/NIAID NIH HHS/United States ; R56 AI056152/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; *Oxidative Stress/drug effects ; *Suppressor of Cytokine Signaling 3 Protein/metabolism ; Mice ; *Suppressor of Cytokine Signaling 1 Protein/metabolism ; Humans ; Inflammation/immunology/drug therapy ; Cornea/metabolism/immunology ; Retinal Pigment Epithelium/metabolism ; Eye Diseases/drug therapy/immunology/metabolism ; Peptides/pharmacology/therapeutic use ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {Several blinding diseases affecting the retina and optic nerve are exacerbated by or caused by dysregulated inflammation and oxidative stress. These diseases include uveitis, age related macular degeneration, diabetic retinopathy and glaucoma. Consequently, despite their divergent symptoms, treatments that reduce oxidative stress and suppress inflammation may be therapeutic. The production of inflammatory cytokines and their activities are regulated by a class of proteins termed Suppressors of Cytokine Signaling (SOCS). SOCS1 and SOCS3 are known to dampen signaling via pathways employing Janus kinases and signal transducer and activator of transcription proteins (JAK/STAT), Toll-like Receptors (TLR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), mitogen activated kinase (MAPK) and NLR family pyrin domain containing 3 (NLRP3). We have developed cell-penetrating peptides from the kinase inhibitory region of the SOCS1 and SOCS3 (denoted as R9-SOCS1-KIR and R9-SOCS3-KIR) and tested them in retinal pigment epithelium (RPE) cells and in macrophage cell lines. SOCS-KIR peptides exhibited anti-inflammatory, anti-oxidant and anti-angiogenic properties. In cell culture, both Th1 and Th17 cells were suppressed together with the inhibition of other inflammatory markers. We also observed a decrease in oxidants and a simultaneous rise in neuroprotective and anti-oxidant effectors. In addition, treatment prevented the loss of gap junction proteins and the ensuing drop in transepithelial electrical resistance in RPE cells. When tested in mouse models by eye drop instillation, they showed protection against autoimmune uveitis, as a prophylactic as well as a therapeutic. Mice with endotoxin-induced uveitis were protected by eye drop administration as well. R9-SOCS3-KIR was particularly effective against the pathways acting through STAT3, e.g. IL-6 and VEGF-A mediated responses that lead to macular degeneration. Eye drop administration of R9-SOCS3-KIR stimulated production of antioxidant effectors and reduced clinical symptoms in mouse model of oxidative stress that replicates the RPE injury occurring in AMD. Because these peptides suppress multiple pathogenic stimuli and because they can be delivered topically to the cornea, they are attractive candidates for therapeutics for uveitis, macular degeneration, diabetic retinopathy and glaucoma.},
}
@article {pmid39104162,
year = {2026},
author = {Huang, X and Zhang, Y and Jiang, Y and Li, T and Yang, S and Wang, Y and Yu, B and Zhou, M and Zhang, G and Zhao, X and Sun, J and Sun, X},
title = {Contribution of ferroptosis and SLC7A11 to light-induced photoreceptor degeneration.},
journal = {Neural regeneration research},
volume = {21},
number = {1},
pages = {406-416},
pmid = {39104162},
issn = {1673-5374},
abstract = {JOURNAL/nrgr/04.03/01300535-202601000-00043/figure1/v/2025-06-09T151831Z/r/image-tiff Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss. Ferroptosis has been demonstrated to be associated with retinal degenerative diseases. However, the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored. Bioinformatics and biochemical analyses in this study revealed xC - , solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model. This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway, through which cystine depletion, iron ion accumulation, and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment. We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo . Conversely, solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H 2 O 2 -induced ferroptosis of 661W cells. These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.},
}
@article {pmid39103390,
year = {2024},
author = {Ye, S and Ma, S and Liu, S and Huang, Y and Li, D and Li, M and Su, T and Luo, J and Zhang, C and Shi, D and Hu, L and Zhang, L and Yu, H and He, M and Shang, X and Zhang, X},
title = {Shared whole environmental etiology between Alzheimer's disease and age-related macular degeneration.},
journal = {npj aging},
volume = {10},
number = {1},
pages = {36},
pmid = {39103390},
issn = {2731-6068},
abstract = {The comorbidity of Alzheimer's disease (AD) and age-related macular degeneration (AMD) has been established in clinical and genetic studies. There is growing interest in determining the shared environmental factors associated with both conditions. Recent advancements in record linkage techniques enable us to identify the contributing factors to AD and AMD from a wide range of variables. As such, we first constructed a knowledge graph based on the literature, which included all statistically significant risk factors for AD and AMD. An environment-wide association study (EWAS) was conducted to assess the contribution of various environmental factors to the comorbidity of AD and AMD based on the UK biobank. Based on the conditional Q-Q plots and Bayesian algorithm, several shared environmental factors were identified, which could be categorized into the domains of health condition, biological sample parameters, body index, and attendance availability. Finally, we generated a shared etiology landscape for AD and AMD by combining existing knowledge with our novel findings.},
}
@article {pmid39101834,
year = {2024},
author = {Khan, H and Aziz, AA and Khanani, Z and Khan, H and Mojumder, O and Gahn, GM and Khanani, AM},
title = {Approved treatments for neovascular age-related macular degeneration: current safety and future directions.},
journal = {Expert opinion on drug safety},
volume = {23},
number = {9},
pages = {1109-1114},
doi = {10.1080/14740338.2024.2387318},
pmid = {39101834},
issn = {1744-764X},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects/pharmacology ; *Macular Degeneration/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Genetic Therapy/methods ; Aged ; Disease Progression ; Ranibizumab/administration &amp; dosage/adverse effects ; Animals ; Drug Delivery Systems ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a progressive retinal degenerative disease that is implicated as one of the leading causes of visual impairment in the elderly population. Vascular endothelial growth factor (VEGF) has been identified as the main driver of AMD, and various therapeutics have revolutionized the treatment and management of neovascular AMD (nAMD) with favorable visual and anatomical outcomes.<br><br>AREAS COVERED: Physicians have a variety of approved therapeutics in their arsenal for patients with varying disease progression and patient-specific needs, with the ultimate goal of achieving optimal visual and anatomic outcomes. The literature search was conducted using PubMed, Google Scholar, and sources from companies' websites, allowing us to locate findings recently presented at conferences.<br><br>EXPERT OPINION: Scientific advancements in the field have led to newly approved therapeutics and devices, such as the port-delivery system with ranibizumab (PDS), and further investigation is ongoing in the realm of gene therapy for retinal diseases. In addition to efficacy and durability, newer agents must have comparable safety profiles to older agents in order to be used broadly. These options introduce a level of complexity in nAMD treatment; however, physicians to personalize treatment to improve vision in nAMD patients and reduce treatment burden overall.},
}
@article {pmid39099595,
year = {2024},
author = {Cheng, S and Zhang, S and Huang, M and Liu, Y and Zou, X and Chen, X and Zhang, Z},
title = {Treatment of neovascular age-related macular degeneration with anti-vascular endothelial growth factor drugs: progress from mechanisms to clinical applications.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1411278},
pmid = {39099595},
issn = {2296-858X},
abstract = {Neovascular age-related macular degeneration (nARMD) is an important cause of visual impairment and blindness in the elderly, with choroidal neovascularization in the macula as the main pathological feature. The onset of nARMD is closely related to factors including age, oxidative stress, and lipid metabolism. Vascular endothelial growth factor (VEGF) is an important factor contributing to nARMD as well as choroidal neovascularization and retinal leakage formation. At present, anti-VEGF therapy is the only treatment that improves vision and halts disease progression in most patients, making anti-VEGF drugs a landmark development for nARMD treatment. Although intravitreal injection of anti-VEGF drugs has become the first-line treatment for nARMD, this treatment has many shortcomings including repeated injections, poor or no response in some patients, and complications such as retinal fibrosis. As a result, several new anti-VEGF drugs are being developed. This review provides a discussion of these new anti-VEGF drugs for the treatment of nARMD.},
}
@article {pmid39099486,
year = {2024},
author = {Huang, YW and Meng, LC and Shen, LJ and Huang, CF and Chen, LK and Hsiao, FY},
title = {Changing Reimbursement Criteria on Anti-VEGF Treatment Patterns Among Wet Age-Related Macular Degeneration and Diabetic Macular Edema Patients: An Interrupted Time Series Analysis.},
journal = {International journal of health policy and management},
volume = {13},
number = {},
pages = {8210},
pmid = {39099486},
issn = {2322-5939},
mesh = {Humans ; *Interrupted Time Series Analysis ; *Macular Edema/drug therapy/economics ; *Diabetic Retinopathy/drug therapy/economics ; Male ; Female ; *Angiogenesis Inhibitors/economics/therapeutic use/administration &amp; dosage ; Taiwan ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Wet Macular Degeneration/drug therapy/economics ; Intravitreal Injections ; Reimbursement Mechanisms ; Middle Aged ; National Health Programs/economics/statistics &amp; numerical data ; Ranibizumab/economics/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; },
abstract = {BACKGROUND: To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan.<br><br>METHODS: An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection.<br><br>RESULTS: The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes.<br><br>CONCLUSION: This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects.},
}
@article {pmid39098637,
year = {2025},
author = {Shaheen, A and Mehra, D and Ghalibafan, S and Patel, S and Buali, F and Panneerselvam, S and Perez, N and Hoyek, S and Flynn, HW and Patel, N and Yannuzzi, NA},
title = {Efficacy and Safety of Anti-VEGF Injections and Surgery for Age-Related Macular Degeneration-Related Submacular Hemorrhage: A Systematic Review and Meta-Analysis.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {1},
pages = {4-12},
doi = {10.1016/j.oret.2024.07.024},
pmid = {39098637},
issn = {2468-6530},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Intravitreal Injections ; *Visual Acuity ; *Retinal Hemorrhage/diagnosis/etiology/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Treatment Outcome ; Vitrectomy/methods ; Bevacizumab/administration &amp; dosage ; },
abstract = {TOPIC: This systematic review and meta-analysis investigates the efficacy and safety of anti-VEGF injections compared with surgical intervention in improving visual acuity (VA) and reducing complications for patients with submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (AMD).<br><br>CLINICAL RELEVANCE: Determining the optimal intervention for SMH in AMD is crucial for patient care.<br><br>METHODS: We included studies on anti-VEGF injections or surgical interventions for SMH in AMD from 7 databases, searched up to May 2024. Data extraction and quality assessment were done by 2 independent reviewers. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis employed random-effects models. Primary outcomes were pooled mean logarithm of the minimum angle of resolution VA difference (initial examination minus last follow-up VA) and adverse events rates.<br><br>RESULTS: A total of 43 observational studies were included: 21 (960 eyes) on anti-VEGF and 22 (455 eyes) on surgery. Comparisons were made across separate studies due to lack of head-to-head studies. Meta-analysis included 11 anti-VEGF studies (444 eyes) and 12 surgical studies (195 eyes) for VA outcomes. The mean difference in VA was&#xa0;-0.16 (95% confidence interval (CI),&#xa0;-0.24 to&#xa0;-0.08) for anti-VEGF and&#xa0;-0.36 (95% CI,&#xa0;-0.68 to&#xa0;-0.04) for surgery, with no significant difference between groups (chi-square&#xa0;= 1.70, df&#xa0;= 1, P&#xa0;= 0.19). Heterogeneity was high in surgical studies (I[2]&#xa0;= 96.2%, &#x3c4;[2]&#xa0;= 0.23, P < 0.01) and negligible in anti-VEGF studies (I[2]&#xa0;= 7%, &#x3c4;[2]&#xa0;= 0.003, P&#xa0;= 0.38). The GRADE certainty was moderate for anti-VEGF and low for surgery. Anti-VEGF had lower rates of cataract (0% vs. 4.6%), proliferative vitreoretinopathy (0.1% vs. 2.0%), and retinal detachment (0.1% vs. 10.6%), but similar rates of recurrent hemorrhage (5.4% vs. 5.3%). Complications were summarized descriptively due to zero-cell problem.<br><br>CONCLUSION: Both anti-VEGF and surgery treat SMH in AMD with similar VA outcomes but different safety profiles. Anti-VEGF is preferred for less severe hemorrhage, whereas surgery is suited for extensive hemorrhage. Despite uncertain comparative VA outcomes, treatment should be guided by clinical judgment and patient factors.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39098587,
year = {2024},
author = {Motipally, SI and Kolson, DR and Guan, T and Kolandaivelu, S},
title = {Aberrant lipid accumulation and retinal pigment epithelium dysfunction in PRCD-deficient mice.},
journal = {Experimental eye research},
volume = {246},
number = {},
pages = {110016},
pmid = {39098587},
issn = {1096-0007},
support = {P20 GM103434/GM/NIGMS NIH HHS/United States ; R01 EY028959/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; *Tomography, Optical Coherence ; *Disease Models, Animal ; Lipid Metabolism ; Mice, Knockout ; Mice, Inbred C57BL ; ATP Binding Cassette Transporter 1/genetics/metabolism ; Cholesterol/metabolism ; Cholesterol Esters/metabolism ; Cone-Rod Dystrophies/metabolism/genetics ; Electroretinography ; Bruch Membrane/metabolism/pathology ; Immunohistochemistry ; Macular Degeneration/congenital ; },
abstract = {Progressive Rod-Cone Degeneration (PRCD) is an integral membrane protein found in photoreceptor outer segment (OS) disc membranes and its function remains unknown. Mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans and multiple dog breeds. PRCD-deficient models exhibit decreased levels of cholesterol in the plasma. However, potential changes in the retinal cholesterol remain unexplored. In addition, impaired phagocytosis observed in these animal models points to potential deficits in the retinal pigment epithelium (RPE). Here, using a Prcd[-/-] murine model we investigated the alterations in the retinal cholesterol levels and impairments in the structural and functional integrity of the RPE. Lipidomic and immunohistochemical analyses show a 5-fold increase in the levels of cholesteryl esters (C.Es) and lipid deposits in the PRCD-deficient retina, respectively, indicating alterations in total retinal cholesterol. Furthermore, the RPE of Prcd[-/-] mice exhibit a 1.7-fold increase in the expression of lipid transporter gene ATP-binding cassette transporter A1 (Abca1). Longitudinal fundus and spectral domain optical coherence tomography (SD-OCT) examinations showed focal lesions and RPE hyperreflectivity. Strikingly, the RPE of Prcd[-/-] mice exhibited age-related pathological features such as lipofuscin accumulation, Bruch's membrane (BrM) deposits and drusenoid focal deposits, mirroring an Age-related Macular Degeneration (AMD)-like phenotype. We propose that the extensive lipofuscin accumulation likely impairs lysosomal function, leading to the defective phagocytosis observed in Prcd[-/-] mice. Our findings support the dysregulation of retinal cholesterol homeostasis in the absence of PRCD. Further, we demonstrate that progressive photoreceptor degeneration in Prcd[-/-] mice is accompanied by progressive structural and functional deficits in the RPE, which likely exacerbates vision loss over time.},
}
@article {pmid39097172,
year = {2024},
author = {Schloesser, L and Klose, SM and Mauschitz, MM and Abdullah, Z and Finger, RP},
title = {The role of immune modulators in age-related macular degeneration.},
journal = {Survey of ophthalmology},
volume = {69},
number = {6},
pages = {851-869},
doi = {10.1016/j.survophthal.2024.07.009},
pmid = {39097172},
issn = {1879-3304},
mesh = {Humans ; *Macular Degeneration/immunology/physiopathology ; *Cytokines/metabolism ; },
abstract = {We provide an overview of the expanding literature on the role of cytokines and immune mediators in pathophysiology of age-related macular degeneration (AMD). Although many immunological mediators have been linked to AMD pathophysiology, the broader mechanistic picture remains unclear with substantial variations in the levels of evidence supporting these mediators. Therefore, we reviewed the literature considering the varying levels of supporting evidence. A Medical Subject Headings (MeSH) term-based literature research was conducted in September, 2023, consisting of the MeSH terms "cytokine" and "Age-related macular degeneration" connected by the operator "AND". After screening the publications by title, abstract, and full text, a total of 146 publications were included. The proinflammatory cytokines IL-1β (especially in basic research studies), IL-6, IL-8, IL-18, TNF-α, and MCP-1 are the most extensively characterised cytokines/chemokines, highlighting the role of local inflammasome activation and altered macrophage function in the AMD pathophysiology. Among the antiinflammatory mediators IL-4, IL-10, and TGF-β were found to be the most extensively characterised, with IL-4 driving and IL-10 and TGF-β suppressing disease progression. Despite the extensive literature on this topic, a profound understanding of AMD pathophysiology has not yet been achieved. Therefore, further studies are needed to identify potential therapeutic targets, followed by clinical studies.},
}
@article {pmid39094557,
year = {2025},
author = {Borrelli, E and Boscia, G and Gelormini, F and Ricardi, F and Ghilardi, A and Marolo, P and Parisi, G and Fallico, M and Lupidi, M and Mariotti, C and Bandello, F and Sadda, S and Reibaldi, M},
title = {Macular thickness and visual acuity are characterized by a quadratic nonlinear relation in previously treated neovascular AMD eyes.},
journal = {European journal of ophthalmology},
volume = {35},
number = {2},
pages = {650-659},
doi = {10.1177/11206721241265998},
pmid = {39094557},
issn = {1724-6016},
mesh = {Humans ; *Visual Acuity/physiology ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Intravitreal Injections ; Follow-Up Studies ; *Macula Lutea/pathology ; Aged, 80 and over ; Ranibizumab/therapeutic use ; Bevacizumab/therapeutic use ; Fluorescein Angiography ; Nonlinear Dynamics ; Middle Aged ; },
abstract = {PURPOSE: To assess the associations between visual acuity (VA) and retinal thickness in age-related macular degeneration (AMD) eyes treated with anti-vascular endothelial growth factor (VEGF) therapy.<br><br>METHODS: Sixty-eight patients with neovascular AMD (68 eyes) undergoing anti-VEGF therapy with two years of follow-up imaging data after the initiation of treatment were retrospectively included. Linear and nonlinear regression analyses with curve fitting estimation were performed to explore the relationship between visual acuity and OCT-based parameters at the 3-month and 24-month follow-up visits. Regression analyses were also performed between visual acuity and the retinal thickness deviation which was calculated as the absolute value of the difference between measured and normative retinal thickness values.<br><br>RESULTS: The VA was not associated with either foveal (R[2&#x2009;]=&#x2009;0.011 and p&#x2009;=&#x2009;.401 at 3 months; R[2&#x2009;]=&#x2009;0.032 and p&#x2009;=&#x2009;.142 at 24 months) or parafoveal (R[2&#x2009;]=&#x2009;0.045 and p&#x2009;=&#x2009;.081 at 3 months; R[2&#x2009;]=&#x2009;0.050 and p&#x2009;=&#x2009;.055 at 24 months) retinal thicknesses. Compared with the linear models, a quadratic function yielded a relative increase in the R[2] coefficients. Conversely, the VA was linearly associated with foveal retinal thickness deviation (R[2&#x2009;]=&#x2009;0.041 and p&#x2009;=&#x2009;.037 at 24 months) and parafoveal retinal thickness deviation (R[2&#x2009;]=&#x2009;0.062 and p&#x2009;=&#x2009;.040 at 3 months; R[2&#x2009;]=&#x2009;0.088 and p&#x2009;=&#x2009;.014 at 24 months) values.<br><br>CONCLUSIONS: Although there was no linear relationship between retinal thickness and VA, a weak but statistically significant linear relationship could be observed when a retinal thickness deviation was considered. This suggests that deviation-based parameters may be beneficial for structure-function correlations in the context of anti-VEGF therapy for neovascular AMD.},
}
@article {pmid39094470,
year = {2024},
author = {Pattanaik, DK and Lakshminarayanan, V and Sharma, NK and Prasad Sahu, A},
title = {Erratum to "Leading edge of the a-wave of the electroretinogram and sodium iodate-induced age-related macular degeneration: A Model" [J. Theor. Biol. 592 (2024) 01-17/111879].},
journal = {Journal of theoretical biology},
volume = {593},
number = {},
pages = {111912},
doi = {10.1016/j.jtbi.2024.111912},
pmid = {39094470},
issn = {1095-8541},
}
@article {pmid39093364,
year = {2024},
author = {Holz, FG and Schmitz-Valckenberg, S},
title = {[Artificial intelligence (AI) in age-related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {121},
number = {8},
pages = {607-608},
doi = {10.1007/s00347-024-02069-7},
pmid = {39093364},
issn = {2731-7218},
mesh = {Humans ; *Artificial Intelligence ; *Macular Degeneration/pathology ; },
}
@article {pmid39093298,
year = {2024},
author = {Xu, Y and Huang, S and Zhou, S and Wang, X and Wei, M and Chen, X and Zong, R and Lin, X and Li, S and Liu, Z and Chen, Q},
title = {Iron Chelator Deferiprone Restores Iron Homeostasis and Inhibits Retinal Neovascularization in Experimental Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {10},
pages = {5},
pmid = {39093298},
issn = {1552-5783},
mesh = {Animals ; *Deferiprone/pharmacology/therapeutic use ; *Mice, Inbred C57BL ; *Iron Chelating Agents/pharmacology/therapeutic use ; Mice ; *Iron/metabolism ; *Homeostasis ; *Disease Models, Animal ; *Mice, Knockout ; *Retinal Neovascularization/metabolism/drug therapy/etiology/pathology ; Fluorescein Angiography ; Receptors, LDL/genetics/metabolism ; Blotting, Western ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Wet Macular Degeneration/drug therapy/metabolism ; STAT3 Transcription Factor/metabolism ; Male ; },
abstract = {PURPOSE: Retinal neovascularization is a significant feature of advanced age-related macular degeneration (AMD) and a major cause of blindness in patients with AMD. However, the underlying mechanism of this pathological neovascularization remains unknown. Iron metabolism has been implicated in various biological processes. This study was conducted to investigate the effects of iron metabolism on retinal neovascularization in neovascular AMD (nAMD).<br><br>METHODS: C57BL/6J and very low-density lipoprotein receptor (VLDLR) knockout (Vldlr-/-) mice, a murine model of nAMD, were used in this study. Bulk-RNA sequencing was used to identify differentially expressed genes. Western blot analysis was performed to test the expression of proteins. Iron chelator deferiprone (DFP) was administrated to the mice by oral gavage. Fundus fluorescein angiography was used to evaluate retinal vascular leakage. Immunofluorescence staining was used to detect macrophages and iron-related proteins.<br><br>RESULTS: RNA sequencing (RNA-seq) results showed altered transferrin expression in the retina and RPE of Vldlr-/- mice. Disrupted iron homeostasis was observed in the retina and RPE of Vldlr-/- mice. DFP mitigated iron overload and significantly reduced retinal neovascularization and vascular leakage. In addition, DFP suppressed the inflammation in Vldlr-/- retinas. The reduced signals of macrophages were observed at sites of neovascularization in the retina and RPE of Vldlr-/- mice after DFP treatment. Further, the IL-6/JAK2/STAT3 signaling pathway was activated in the retina and RPE of Vldlr-/- mice and reversed by DFP treatment.<br><br>CONCLUSIONS: Disrupted iron metabolism may contribute to retinal neovascularization in nAMD. Restoring iron homeostasis by DFP could be a potential therapeutic approach for nAMD.},
}
@article {pmid39093297,
year = {2024},
author = {Boscia, G and Bacherini, D and Vujosevic, S and Grassi, MO and Borrelli, E and Giancipoli, E and Landini, L and Pignataro, M and Alessio, G and Boscia, F and Viggiano, P},
title = {Long-Term Impact of Diabetic Retinopathy on Response to Anti-VEGF Treatment in Neovascular AMD.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {10},
pages = {6},
pmid = {39093297},
issn = {1552-5783},
mesh = {Humans ; *Diabetic Retinopathy/drug therapy/diagnosis/physiopathology ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use ; *Tomography, Optical Coherence ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Intravitreal Injections ; *Visual Acuity/physiology ; Aged ; *Fluorescein Angiography ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Follow-Up Studies ; Middle Aged ; Ranibizumab/therapeutic use/administration &amp; dosage ; Bevacizumab/therapeutic use ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Treatment Outcome ; Fundus Oculi ; Time Factors ; Recombinant Fusion Proteins ; },
abstract = {PURPOSE: To explore the long-term effect of diabetic retinopathy on response to anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration-associated type 1 macular neovascularization (MNV) using optical coherence tomography angiography (OCTA).<br><br>METHODS: A total of 45 eyes with exudative neovascular age-related macular degeneration (nAMD) with type 1 MNV were included in the analysis. Among them, 24 eyes of 24 patients had no history of diabetes mellitus (DM) in their anamnesis and were assigned to the Not Diabetic group; 21 eyes of 21 patients had mild diabetic retinopathy and were included in the Diabetic group. We considered the following outcome measures: (1) best-corrected visual acuity changes; (2) central macular thickness; (3) MNV lesion area; and (4) MNV flow area. The OCTA acquisitions were performed at the following time points: (1) baseline visit, which corresponded to the day before the first injection; (2) post-loading phase (LP), which was scheduled at 1&#xa0;month after the last LP injection; and (3) 12-month follow-up visit.<br><br>RESULTS: All morphofunctional parameters showed a significant improvement after the LP and at the 12-month follow-up visit. Specifically, both the Diabetic group and the Not Diabetic group displayed a significant reduction of MNV lesion areas at both the post-LP assessment (P = 0.026 and P = 0.016, respectively) and the 12-month follow-up (P = 0.039 and P = 0.025, respectively). Similarly, the MNV flow area was significantly decreased in both the Diabetic group and the Not Diabetic group at the post-LP assessment (P < 0.001 and P = 0.012, respectively) and at the 12-month follow-up (P = 0.01 and P = 0.035, respectively) compared to baseline. A smaller reduction in the MNV lesion area was observed in the Diabetic group at both the post-LP evaluation (P = 0.015) and the 12-month follow-up (P = 0.032). No other significant differences were found between the groups for the other parameters (P > 0.05).<br><br>CONCLUSIONS: Our results indicated that the Diabetic group exhibited a smaller reduction in MNV lesion area after 12&#xa0;months of anti-VEGF treatment. This highlights the importance of considering diabetic retinopathy as a potential modifier of treatment outcomes in nAMD management, with DM serving as a crucial risk factor during anti-angiogenic treatment.},
}
@article {pmid39092383,
year = {2024},
author = {Borkenstein, AF and Borkenstein, EM and Presser, A},
title = {Calculated Drug Concentrations in Currently Available Intravitreal Therapies: Determination of Dilution Factor and Deviation From Recommended Doses.},
journal = {Cureus},
volume = {16},
number = {7},
pages = {e65888},
pmid = {39092383},
issn = {2168-8184},
abstract = {In ophthalmology, intravitreal therapies are currently not personalized/customized and are not adjusted to the individual vitreous volume. With reference to the recently published calculation formula for a more accurate estimation of the vitreous body, we determined the dose of intravitreal medication for different vitreous volumes and compared them with the average volume. Using the axial length of the eye, the formula for the vitreous volume exact (VIVEX) can provide a more accurate indication of the vitreous volume in individual cases than an assumed standard volume of 4 mL. The concentration of active substances in small eyes may be twice as high as that in normal-sized emmetropic eyes. In contrast, large eyes may show less than half of the recommended drug concentration. The calculated concentrations of the investigated intravitreal drugs in small and large eyeballs showed impressive differences with large deviations from the recommended doses. Further systematic studies should follow to find out whether this has any impact on the effectiveness or side effects of the injected drugs.},
}
@article {pmid39091897,
year = {2024},
author = {Farashi, S and Bonelli, R and Jackson, VE and Ansell, BRE and Guymer, RH and Bahlo, M},
title = {Decreased Circulating Very Small Low-Density Lipoprotein is Likely Causal for Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {5},
pages = {100535},
pmid = {39091897},
issn = {2666-9145},
abstract = {OBJECTIVE: Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models. However, whether particular metabolites causally affect the disease has yet to be established.<br><br>DESIGN: A 3-tiered analysis of blood metabolites in the United Kingdom (UK) Biobank cohort to identify metabolites that differ in AMD patients with evidence for a putatively causal role in AMD.<br><br>PARTICIPANTS: A total of 72&#xa0;376 donors from the UK Biobank cohort including participants with AMD (N&#xa0;=&#xa0;1353) and non-AMD controls (N&#xa0;=&#xa0;71&#xa0;023).<br><br>METHODS: We analyzed 325 directly measured or derived blood metabolites from the UK Biobank for 72&#xa0;376 donors to identify AMD-associated metabolites. Genome-wide association studies for 325 metabolites in 98&#xa0;316 European participants from the UK Biobank were performed. The causal effects of these metabolites in AMD were tested using a 2-sample Mendelian randomization approach. The predictive value of these measurements together with sex and age was assessed by developing a machine learning classifier.<br><br>MAIN OUTCOME MEASURES: Evaluating metabolic biomarkers associated with AMD susceptibility and investigating their potential causal contribution to the development of the disease.<br><br>RESULTS: This study noted age to be the prominent risk factor associated with AMD development. While accounting for age and sex, we identified 84 metabolic markers as significantly (false discovery rate-adjusted P value < 0.05) associated with AMD. Lipoprotein subclasses comprised the majority of the AMD-associated metabolites (39%) followed by several lipoprotein to lipid ratios. Nineteen metabolites showed a likely causative role in AMD etiology. Of these, 6 lipoproteins contain very small, very low-density lipoprotein (VLDL), and phospholipids to total lipid ratio in medium VLDL. Based on this we postulate that depletion of circulating very small VLDLs is likely causal for AMD. The risk prediction model constructed from the metabolites, age and sex, identified age as the primary predictive factor with a much smaller contribution by metabolites to AMD risk prediction.<br><br>CONCLUSIONS: This study underscores the pronounced role of lipids in AMD susceptibility and the likely causal contribution of particular subclasses of lipoproteins to AMD. Our study provides valuable insights into the metabopathological mechanisms of AMD disease development and progression.},
}
@article {pmid39091492,
year = {2024},
author = {Gill, K and Yoo, HS and Chakravarthy, H and Granville, DJ and Matsubara, JA},
title = {Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1421175},
pmid = {39091492},
issn = {1664-3224},
mesh = {Humans ; *Fibrosis ; Animals ; *Macular Degeneration/pathology/metabolism/etiology ; *Granzymes/metabolism ; Retina/pathology/metabolism/immunology ; Mast Cells/immunology/metabolism ; Choroidal Neovascularization/pathology/metabolism ; },
abstract = {Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis.},
}
@article {pmid39090513,
year = {2024},
author = {Holekamp, NM and Yaqub, M and Ranade, SV and Cantrell, RA and Singh, S and Gazzard, G},
title = {Systematic Literature Reviews Comparing the Long-Term Safety Outcomes for the Port Delivery System with Ranibizumab (PDS) Versus Other Ocular Implants.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {9},
pages = {2303-2329},
pmid = {39090513},
issn = {2193-8245},
abstract = {OBJECTIVES: To determine whether the types and rates of post-surgical complications associated with the Port Delivery System with ranibizumab (PDS) are comparable with those reported for other ocular implants that cross the sclera.<br><br>METHODS: Systematic literature reviews were conducted to determine the long-term (&#x2265;&#x2009;18-month) safety of ocular implants that cross the sclera in clinical trials and real-world studies. Complication types and rates were compared with those reported for the PDS in phase III clinical trials (Archway, Pagoda, and Pavilion).<br><br>RESULTS: Sixteen clinical trials (24 publications) and 43 real-world studies were identified reporting 30 complications in eyes with 15 implant types and 8 ocular diseases. Implants were associated with an acceptable, well-characterized safety profile, with most complications resolving spontaneously or with treatment. Device-related complications were reported in 0.7% (0.0-5.0%) of study eyes in clinical trials and 1.3% (0.0-14.5%) of eyes in real-world studies. Rates of conjunctival complications were 2.1% (0.0-22.8%) and 2.2% (0.9-4.6%), respectively. The overall types and rates of adverse events of special interest reported for the PDS in phase III trials (cataract, conjunctival bleb, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, endophthalmitis, implant dislocation, retinal detachment, and hyphema) were within the ranges reported for other ocular implants.<br><br>CONCLUSIONS: The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera. This suggests that the long-term safety of the PDS is consistent with other ocular devices established in ophthalmology clinical practice.<br><br>TRIAL REGISTRATION: PROSPERO international prospective register of systematic reviews: CRD5202234129, CRD42022343129.},
}
@article {pmid39089734,
year = {2024},
author = {Gedtal, M and Woodside, J and Wright, D and Rayman, M and Hogg, RE},
title = {Subscapular skinfold thickness, not other anthropometric and dual-energy X-ray absorptiometry-measured adiposity, is positively associated with the presence of age-related macular degeneration: a cross-sectional study from National Health and Nutrition Examination Survey 2005-2006.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {39089734},
issn = {2397-3269},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; *Absorptiometry, Photon ; Aged ; *Skinfold Thickness ; *Adiposity ; *Macular Degeneration/epidemiology/diagnostic imaging ; *Nutrition Surveys ; Adult ; United States/epidemiology ; Body Mass Index ; Risk Factors ; },
abstract = {OBJECTIVE: Current literature reveals an association between anthropometric measures of adiposity (AnthM) and age-related macular degeneration (AMD), but few have explored the disease association with imaging methods. This study aimed to explore the relationship between AMD status and dual-energy X-ray absorptiometry measures (DEXAMs) among a representative sample of the US population, and compare the association with AnthM.<br><br>METHOD: Using a representative sample in the National Health and Nutrition Examination Study 2005-2006 (n=1632), DEXAMs across the whole body and waist (ie, android), and relative fat distributions (eg, percentage fat, android-to-total body ratio) were analysed between no AMD (baseline) and any AMD. Bivariate analyses across AMD status were similarly performed for AnthM (ie, body mass index, waist circumference and skinfold thicknesses) and potential confounders (ie, demographics and health-related variables). Significant adiposity measures were analysed using logistic regression, adjusting for confounders.<br><br>RESULTS: The participants in the sample were aged 40-69 years, were majority female (52%) and mainly Caucasian (76.5%). Bivariate analysis revealed having any AMD had positive significant associations with android-to-total fat ratio and subscapular skinfold thickness (SSFT). Other AnthM and DEXAMs were not significant. After adjusting age, gender and prescription of cholesterol-lowering medicine, only SSFT remained significantly associated.<br><br>CONCLUSION: SSFT represents an independent risk factor for AMD presence compared with other AnthM and DEXAMs. SSFT is an established method of measuring fat under the skin (ie, subcutaneous fat). Hence, subcutaneous fat may be more relevant in explaining the adiposity-AMD link due to physiological properties specific to the tissue. Limitations include the restricted age range and low numbers of participants with late AMD.},
}
@article {pmid39089690,
year = {2024},
author = {Chaudhary, A and Abbott, CJ and Wu, Z and Fang, WY and Raj, PR and Naughton, M and Heriot, WJ and Guymer, RH},
title = {Nocturnal hypoxia and age-related macular degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {9},
pages = {973-980},
pmid = {39089690},
issn = {1442-9071},
support = {2008382//National Health &amp; Medical Research Council of Australia/ ; GNT1103013//National Health &amp; Medical Research Council of Australia/ ; GNT1181010//National Health &amp; Medical Research Council of Australia/ ; },
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; *Hypoxia/physiopathology/diagnosis ; Aged ; Middle Aged ; *Sleep Apnea, Obstructive/diagnosis/physiopathology/complications ; *Oximetry ; Risk Factors ; Geographic Atrophy/diagnosis/physiopathology ; Aged, 80 and over ; Tomography, Optical Coherence/methods ; Wet Macular Degeneration/diagnosis/physiopathology ; Macular Degeneration/diagnosis/physiopathology/complications ; Multimodal Imaging ; Fluorescein Angiography/methods ; Retinal Drusen/diagnosis ; },
abstract = {BACKGROUND: Nocturnal hypoxia is common, under-diagnosed and is found in the same demographic at risk of age-related macular degeneration (AMD). The objective of this study was to determine any association between nocturnal hypoxia and AMD, its severity, and the high-risk sub-phenotype of reticular pseudodrusen (RPD).<br><br>METHODS: This cross-sectional study included participants aged &#x2265;50&#x2009;years with AMD, or normal controls, exclusive of those on treatment for obstructive sleep apnoea. All participants had at home, overnight (up to 3 nights) pulse oximetry recordings and multimodal imaging to classify AMD. Classification of Obstructive Sleep Apnea (OSA) was determined based on oxygen desaturation index [ODI] with mild having values of 5-15 and moderate-to-severe >15.<br><br>RESULTS: A total of 225 participants were included with 76% having AMD, of which 42% had coexistent RPD. Of the AMD participants, 53% had early/intermediate AMD, 30% had geographic atrophy (GA) and 17% had neovascular AMD (nAMD). Overall, mild or moderate-to-severe OSAwas not associated with an increased odds of having AMD nor AMD with RPD (p&#x2009;&#x2265;&#x2009;0.180). However, moderate-to-severe OSA was associated with increased odds of having nAMD (odds ratio&#x2009;=&#x2009;6.35; 95% confidence interval&#x2009;=&#x2009;1.18 to 34.28; p&#x2009;=&#x2009;0.032), but not early/intermediate AMD or GA, compared to controls (p&#x2009;&#x2265;&#x2009;0.130). Mild OSA was not associated with differences in odds of having AMD of any severity (p&#x2009;&#x2265;&#x2009;0.277).<br><br>CONCLUSIONS: There was an association between nocturnal hypoxia as measured by the ODI and nAMD. Hence, nocturnal hypoxia may be an under-appreciated important modifiable risk factor for nAMD.},
}
@article {pmid39089359,
year = {2024},
author = {Yang, Z and Zhang, J and Zheng, Y},
title = {Associations Between Life's Essential 8 and Major Ocular Diseases in the American Middle-Aged and Elderly Population.},
journal = {American journal of ophthalmology},
volume = {268},
number = {},
pages = {76-85},
doi = {10.1016/j.ajo.2024.07.022},
pmid = {39089359},
issn = {1879-1891},
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; Middle Aged ; Aged ; United States/epidemiology ; *Nutrition Surveys ; Risk Factors ; *Eye Diseases/epidemiology ; Cardiovascular Diseases/epidemiology ; Health Status ; Adult ; Algorithms ; Aged, 80 and over ; Odds Ratio ; },
abstract = {PURPOSE: To explore the correlation between cardiovascular health (CVH) and ocular diseases, given their shared risk factors and biological mechanisms, this study utilizes the newly updated Life's Essential 8 (LE8) algorithm.<br><br>DESIGN: A cross-sectional study.<br><br>METHODS: This analysis, conducted from February 15 to April 1, 2024, in Changchun, includes data from 4146 participants aged 40 and above, drawn from the National Health and Nutrition Examination Survey database (2005-2008). It covers information on visual health status, dietary habits through interviews, and professional ophthalmological examinations. Participants' CVH status was assessed using the LE8 algorithm, and relationships with major ocular diseases such as retinopathy, cataracts, diabetic retinopathy, glaucoma, and age-related macular degeneration were explored through weighted logistic regression analysis, restricted cubic splines, stratified analysis, and sensitivity analysis.<br><br>RESULTS: After multivariable adjustment, lower LE8 scores showed a significant positive relationship with any ocular disease (odds ratio [OR]: 2.03, 95% confidence interval [CI]: 1.39-2.96, P = .001), any objectively determined ocular disease (OR: 2.24, 95% CI: 1.48-3.38, P < .001), retinopathy (OR: 2.88, 95% CI: 1.89-4.41, P < .001), diabetic retinopathy (OR: 10.23, 95% CI: 3.11-33.61, P < .001), and glaucoma (OR: 2.76, 95% CI: 1.47-5.21, P = .003), with all trends significant (all P < .01). Additionally, lower scores in the behavioral subdomain were significantly correlated with an elevated risk of cataracts (OR: 1.45, 95% CI: 1.03-2.04). Subgroup analyses revealed more pronounced negative correlations between LE8 and retinopathy among females and those suffering from chronic kidney disease.<br><br>CONCLUSIONS: A low CVH score was linked to an increased likelihood of ocular diseases in a US-populated-based study. This correlation supports the potential benefits of enhancing cardiovascular wellness to mitigate the development of ocular conditions.},
}
@article {pmid39089062,
year = {2024},
author = {Pongsachareonnont, PF and Sakthong, P and Chaikitmongkol, V and Tsutsumi, WD and Bhoomibunchoo, C and Hurst, CP and Teerawattananon, Y and Kulvichit, K},
title = {Health Utility Values Among Patients With Diabetic Retinopathy, Wet Age-Related Macular Degeneration, and Cataract in Thailand: A Multicenter Survey Using Time Trade-Off, EQ-5D-5L, and Health Utility Index 3.},
journal = {Value in health regional issues},
volume = {44},
number = {},
pages = {101030},
doi = {10.1016/j.vhri.2024.101030},
pmid = {39089062},
issn = {2212-1102},
mesh = {Humans ; Male ; *Diabetic Retinopathy/psychology/epidemiology ; Female ; Thailand/epidemiology ; Cross-Sectional Studies ; *Quality of Life/psychology ; *Cataract/psychology/complications/epidemiology/physiopathology ; Middle Aged ; Surveys and Questionnaires ; Aged ; *Visual Acuity ; Wet Macular Degeneration/psychology/complications/epidemiology ; },
abstract = {OBJECTIVES: This study aimed to establish normative health utility data in Thai patients with diabetic retinopathy, wet age-related macular degeneration, and cataract; evaluate the sensitivity of different utility instruments to visual impairment; explore the relationship among these health utility values with the vision-specific quality of life (QoL); and assess the association of baseline characteristics and visual acuity level with health utility values and vision-specific QoL.<br><br>METHODS: This multicenter cross-sectional survey included 309 patients from tertiary eye centers. We used health utility instruments (time trade-off [TTO], EuroQol five-dimension [EQ-5D-5L], and Health Utility Index 3 [HUI3]) and vision-specific QoL instrument (National Eye Institute Visual Function Questionnaire) for face-to-face interviews. Demographic data and Early Treatment Diabetic Retinopathy Study visual acuity were recorded during the participants ophthalmic visits. Univariable and multivariable mixed-effect models were used to evaluate factors associated with the utility scores. Health utility scores among each type of eye disease were compared.<br><br>RESULTS: The overall mean utility values from the TTO, EQ-5D-5L, and HUI3 were 0.84 &#xb1; 0.25, 0.70 &#xb1; 0.19, and 0.68 &#xb1; 0.26, respectively. The health utility scores obtained from TTO and HUI3 showed a significant response to severe visual impairment or worse. Health utility scores from HUI3 (r&#xa0;= 0.54; P < .01) and EQ-5D-5L (r&#xa0;= 0.43; P < .01) displayed a moderate correlation with the National Eye Institute Visual Function Questionnaire score. There were no significant differences in health utility value among the 3 diseases upon adjusting for the visual acuity level and demographics.<br><br>CONCLUSIONS: Visual acuity level has a greater impact on a patient's QoL than the type of eye disease. HUI3 and EQ-5D-5L and TTO are suitable for measuring health utility in leading causes of blindness.},
}
@article {pmid39087929,
year = {2024},
author = {Carvajal, N and Yang, D and Nava, K and Kedia, A and Keenan, JD and Yiu, G and Stewart, JM},
title = {Intergrader Agreement in Grading Optical Coherence Tomography Morphologic Features in Eyes With Intermediate Nonexudative Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {8},
pages = {3},
pmid = {39087929},
issn = {2164-2591},
support = {R01 EY032238/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Aged ; Female ; Male ; Reproducibility of Results ; *Macular Degeneration/diagnostic imaging/pathology ; Observer Variation ; Middle Aged ; Aged, 80 and over ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Retinal Drusen/diagnostic imaging/pathology ; Severity of Illness Index ; },
abstract = {PURPOSE: To determine the reliability of a nine-point summary scale for grading intermediate age-related macular degeneration (AMD) image morphologic features based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid.<br><br>METHODS: Two trained graders independently divided spectral domain-optical coherence tomography (SD-OCT) scans into nine subfields and then graded each subfield for the presence of intraretinal hyperreflective foci (HRF), reticular pseudodrusen (RPD), and incomplete or complete retinal pigment epithelium and outer retinal atrophy (iRORA or cRORA). Grading results were assessed by summing the subfield grades into a nine-point summary score and also by using an eye-level binary grade for presence of the finding in any subfield. Gwet's first-order agreement coefficient (AC1) was calculated to assess intergrader agreement.<br><br>RESULTS: Images of 79 eyes from 52 patients were evaluated. Intergrader agreement was higher when the OCT grades were summarized with a nine-point summary score (Gwet's AC1 0.92, 0.89, 0.99, and 0.99 for HRF, RPD, iRORA, and cRORA, respectively) compared with the eye-level binary grade (Gwet's AC1 0.75, 0.76, 0.97, and 0.96 for HRF, RPD, iRORA, and cRORA, respectively), with significant differences detected for HRF and RPD.<br><br>CONCLUSIONS: The use of a nine-point summary score showed higher reliability in grading when compared to the binary subfield- and eye-level data, and thus may offer more precise estimation of AMD disease staging.<br><br>TRANSLATIONAL RELEVANCE: These findings suggest that a nine-point summary score could be a useful means of disease staging by using findings on OCT in clinical studies of AMD.},
}
@article {pmid39087629,
year = {2024},
author = {Hyttinen, JMT and Koskela, A and Blasiak, J and Kaarniranta, K},
title = {Autophagy in drusen biogenesis secondary to age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {7},
pages = {759-772},
doi = {10.1111/aos.16744},
pmid = {39087629},
issn = {1755-3768},
support = {333302//The Academy of Finland/ ; 5503770//Kuopio University Hospital VTR grant/ ; },
mesh = {Humans ; *Autophagy/physiology ; *Retinal Drusen/metabolism/etiology ; *Macular Degeneration/metabolism/etiology ; *Retinal Pigment Epithelium/metabolism/pathology ; Oxidative Stress/physiology ; },
abstract = {Age-related macular degeneration (AMD) is an emerging cause of blindness in aged people worldwide. One of the key signs of AMD is the degeneration of the retinal pigment epithelium (RPE), which is indispensable for the maintenance of the adjacent photoreceptors. Because of impaired energy metabolism resulting from constant light exposure, hypoxia, and oxidative stress, accumulation of drusen in AMD-affected eyes is observed. Drusen contain damaged cellular proteins, lipoprotein particles, lipids and carbohydrates and they are related to impaired protein clearance, inflammation, and extracellular matrix modification. When autophagy, a major cellular proteostasis pathway, is impaired, the accumulations of intracellular lipofuscin and extracellular drusen are detected. As these aggregates grow over time, they finally cause the disorganisation and destruction of the RPE and photoreceptors leading to visual loss. In this review, the role of autophagy in drusen biogenesis is discussed since impairment in removing cellular waste in RPE cells plays a key role in AMD progression. In the future, means which improve intracellular clearance might be of use in AMD therapy to slow the progression of drusen formation.},
}
@article {pmid39085595,
year = {2024},
author = {Chu, J and Shaia, JK and Sharma, N and Russell, MW and Rachitskaya, AV and Talcott, KE and Singh, RP},
title = {Characterization and prevalence of ocular comorbidities and risk of legal blindness across the United States.},
journal = {Eye (London, England)},
volume = {38},
number = {16},
pages = {3118-3124},
pmid = {39085595},
issn = {1476-5454},
support = {UL1 TR002548/TR/NCATS NIH HHS/United States ; UL1TR002548//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; T32 EY024236/EY/NEI NIH HHS/United States ; UM1 TR004528/TR/NCATS NIH HHS/United States ; P30EY025585(BA-A)//Research to Prevent Blindness (RPB)/ ; P30 EY025585/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Male ; United States/epidemiology ; Female ; Prevalence ; Retrospective Studies ; Cross-Sectional Studies ; Middle Aged ; Aged ; *Comorbidity ; *Diabetic Retinopathy/epidemiology ; *Blindness/epidemiology ; Adult ; Risk Factors ; Glaucoma/epidemiology ; Uveitis/epidemiology ; Retinal Vein Occlusion/epidemiology ; Aged, 80 and over ; Eye Diseases/epidemiology ; },
abstract = {BACKGROUND/OBJECTIVES: Vision loss is a top disability in the United States (US). Patients commonly present with multiple ocular diseases, but the extent to which this places them at risk for vision loss, and if sex and race impacts this, is poorly understood. This exploratory analysis evaluated which ocular comorbidities and demographics are at highest risk for visual impairment.<br><br>SUBJECTS/METHODS: A retrospective cross-sectional study was conducted through the TriNetX Analytics Network, an aggregated network encompassing over 90 million insured and uninsured patients across 50 healthcare organizations from all regions in the US. Patients with diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), glaucoma, and uveitis were included in this study. Ocular diseases and visual impairment were determined through ICD-10 codes. Prevalence and odds ratios were calculated while stratifying by sex and racial demographics. Statistical analyses were completed using RStudio and Excel with 95% confidence intervals calculated.<br><br>RESULTS: The comorbid conditions with the highest prevalence of visual impairment were uveitis and RVO (39.94%), uveitis and neovascular AMD (37.61%), and uveitis and glaucoma (33.23%). The comorbidity with the highest odds for visual impairment was uveitis and RVO (POR 4.86; 95% CI 4.49, 5.26). Compared to white males, Black and Hispanic males were disproportionately affected by visual impairment across ocular comorbidities.<br><br>CONCLUSION: This study quantified the prevalence and odds of visual impairment for unilateral and comorbid ocular disease, with the addition of uveitis causing the greatest increase. Black and Hispanic males were disproportionately affected by visual impairment across comorbid conditions.},
}
@article {pmid39085593,
year = {2024},
author = {Gadiollet, E and Kodjikian, L and Vasson, F and Kodaday, K and Chirpaz, N and Wolff, B and De Bats, F and Feldman, A and Pradat, P and Gascon, P and Mathis, T},
title = {Effect of baseline fluid localization on visual acuity and prognosis in type 1 macular neovascularization treated with anti-VEGF.},
journal = {Eye (London, England)},
volume = {38},
number = {16},
pages = {3161-3168},
pmid = {39085593},
issn = {1476-5454},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Subretinal Fluid ; Aged ; Prospective Studies ; Prognosis ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged, 80 and over ; Ranibizumab/administration &amp; dosage/therapeutic use ; Fluorescein Angiography/methods ; Bevacizumab/therapeutic use/administration &amp; dosage ; Middle Aged ; },
abstract = {PURPOSE: To assess the prognostic value of subretinal (SRF) and intraretinal fluid (IRF) localizations in type 1 macular neovascularization (MNV) due to age-related macular degeneration (AMD).<br><br>SUBJECTS: Eyes were prospectively treated with anti-vascular epithelial growth factor (anti-VEGF) intravitreal injections (IVT) according to a Pro-Re-Nata (PRN) or Treat and Extend (TAE) regimen during 24 months. A total of 211 eyes with treatment-na&#xef;ve type 1 MNV secondary to AMD were consecutively included. Eyes were divided between 2 groups according to the fluid localization: presence of SRF alone (SRF group), or presence of IRF associated or not with SRF (IRF&#x2009;&#xb1;&#x2009;SRF group).<br><br>RESULTS: At baseline the mean BCVA was 66.2 letters. SRF was present in 94.8% of eyes, IRF in 30.8%, and both in 25.6%. Data were available for 201 eyes at 12 months, and 157 eyes at 24 months. The presence of IRF at baseline was associated with lower baseline BCVA and significantly lower BCVA at 12 months (p&#x2009;<&#x2009;0.001) and 24 months (p&#x2009;<&#x2009;0.001). Eyes with SRF alone displayed better visual outcomes (BCVA at month 12, SRF&#x2009;=&#x2009;74.3 letters, IRF&#x2009;&#xb1;&#x2009;SRF&#x2009;=&#x2009;56.9 letters). In the presence of baseline IRF, fibrosis (p&#x2009;=&#x2009;0.03) and atrophy (p&#x2009;<&#x2009;0.001) were more frequently found at 24 months. In a multivariate model, the presence of baseline IRF was significantly associated with lower BCVA at month 12 but not at month 24.<br><br>CONCLUSION: In type 1 MNV, the presence of baseline IRF was associated with worse visual outcomes compared to SRF alone, and more frequent atrophy and fibrosis.},
}
@article {pmid39084554,
year = {2025},
author = {Sim, SY and Chalkiadaki, E and Koutsocheras, G and Nicholson, L and Sivaprasad, S and Patel, PJ and Selvam, S and Pal, B and Keane, PA and Bhatia, B and Hamilton, R and , },
title = {Real-World 1-Year Outcomes of Treatment-Intensive Neovascular Age-Related Macular Degeneration Switched to Faricimab.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {1},
pages = {22-30},
doi = {10.1016/j.oret.2024.07.020},
pmid = {39084554},
issn = {2468-6530},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Ranibizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Follow-Up Studies ; *Tomography, Optical Coherence/methods ; Treatment Outcome ; Time Factors ; Drug Substitution ; Aged, 80 and over ; Macula Lutea/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To report 1-year anatomic and functional real-world outcomes of patients with treatment-intensive neovascular age-related macular degeneration (nAMD) switched to faricimab.<br><br>DESIGN: Retrospective multicenter cohort study.<br><br>SUBJECTS: Consecutive nAMD patients on 4-weekly treatment interval with either ranibizumab or aflibercept 2 mg in the last 3 visits within a treat-and-extend protocol (high treatment burden) before switch to faricimab at Moorfields Eye Hospital between September 5, 2022 and December 5,&#xa0;2022.<br><br>METHODS: Patients with nAMD switched to faricimab were identified from electronic medical records and those who met criteria of high treatment burden were included. Data collected included preswitch and postswitch visual acuity (VA), treatment intervals, baseline macular morphology, central subfield thickness (CST), macular fluid status, and adverse events.<br><br>MAIN OUTCOME MEASURES: Visual acuity, CST, presence of intraretinal fluid, subretinal fluid, and injection intervals over 1 year after switch to faricimab.<br><br>RESULTS: A total of 130 of 286 (45.5%) eyes met inclusion criteria of being switched due to high treatment burden and 117 were included in analysis. Before switch, these eyes received mean total number of injections of 33.4 &#xb1; 19.6 over a mean of 51.3 &#xb1; 34.9 months. Mean number of injections in 12 months preceding switch was 10.1 &#xb1; 1.6 and mean interval of the preceding 3 injections was 4.2 &#xb1; 0.3 weeks. Mean VA, CST, and percentage of patients with dry macula before switch were 66.0 &#xb1; 11.9 ETDRS letters, 259.6 &#xb1; 76.0 &#x3bc;m and 18.3% respectively. After switch, there was no statistical difference in mean VA throughout follow-up period. Mean CST statistically significantly reduced after the third faricimab injection and at 12 months by 20.0 &#x3bc;m (P&#xa0;=&#xa0;0.035) and 22.1 &#x3bc;m (P&#xa0;= 0.041) respectively. Mean treatment intervals increased to 6.9 &#xb1; 2.3 weeks (P&#xa0;<&#xa0;0.005) at 12 months with 42.9% and 11.4% of patients being on &#x2265;8-weekly and &#x2265;12-weekly treatment intervals, respectively.<br><br>CONCLUSIONS: At 12 months, nAMD patients with previous record of high treatment burden when switched to faricimab maintained VAs and improved anatomic outcomes on extended treatment intervals. Physician bias is inherent in these types of observational studies so a prospective, randomized, controlled trial is recommended to validate these findings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39083095,
year = {2024},
author = {von der Emde, L and Künzel, SH and Pfau, M and Morelle, O and Liermann, Y and Chang, P and Pfau, K and Thiele, S and Holz, FG},
title = {[Use of artificial intelligence for recognition of biomarkers in intermediate age-related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {121},
number = {8},
pages = {609-615},
pmid = {39083095},
issn = {2731-7218},
mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging/pathology ; *Artificial Intelligence ; *Tomography, Optical Coherence/methods ; *Biomarkers/metabolism/analysis ; Retinal Drusen/diagnostic imaging/diagnosis/metabolism ; Sensitivity and Specificity ; Image Interpretation, Computer-Assisted/methods ; Algorithms ; },
abstract = {Advances in imaging and artificial intelligence (AI) have revolutionized the detection, quantification and monitoring for the clinical assessment of intermediate age-related macular degeneration (iAMD). The iAMD incorporates a broad spectrum of manifestations, which range from individual small drusen, hyperpigmentation, hypopigmentation up to early stages of geographical atrophy. Current high-resolution imaging technologies enable an accurate detection and description of anatomical features, such as drusen volumes, hyperreflexive foci and photoreceptor degeneration, which are risk factors that are decisive for prediction of the course of the disease; however, the manual annotation of these features in complex optical coherence tomography (OCT) scans is impractical for the routine clinical practice and research. In this context AI provides a solution by fully automatic segmentation and therefore delivers exact, reproducible and quantitative analyses of AMD-related biomarkers. Furthermore, the application of AI in iAMD facilitates the risk assessment and the development of structural endpoints for new forms of treatment. For example, the quantitative analysis of drusen volume and hyperreflective foci with AI algorithms has shown a correlation with the progression of the disease. These technological advances therefore improve not only the diagnostic precision but also support future targeted treatment strategies and contribute to the prioritized target of personalized medicine in the diagnostics and treatment of AMD.},
}
@article {pmid39083094,
year = {2024},
author = {Chang, P and von der Emde, L and Pfau, M and Künzel, S and Fleckenstein, M and Schmitz-Valckenberg, S and Holz, FG},
title = {[Use of artificial intelligence in geographic atrophy in age-related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {121},
number = {8},
pages = {616-622},
pmid = {39083094},
issn = {2731-7218},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Artificial Intelligence ; *Macular Degeneration/diagnosis/pathology ; *Tomography, Optical Coherence ; Fluorescein Angiography ; Sensitivity and Specificity ; },
abstract = {The first regulatory approval of treatment for geographic atrophy (GA) secondary to age-related macular degeneration in the USA constitutes an important milestone; however, due to the nature of GA as a non-acute, insidiously progressing pathology, the ophthalmologist faces specific challenges concerning risk stratification, making treatment decisions, monitoring of treatment and patient education. Innovative retinal imaging modalities, such as fundus autofluorescence (FAF) and optical coherence tomography (OCT) have enabled identification of typical morphological alterations in relation to GA, which are also suitable for the quantitative characterization of GA. Solutions based on artificial intelligence (AI) enable automated detection and quantification of GA-specific biomarkers on retinal imaging data, also retrospectively and over time. Moreover, AI solutions can be used for the diagnosis and segmentation of GA as well as the prediction of structure and function without and under GA treatment, thereby making a valuable contribution to treatment monitoring and the identification of high-risk patients and patient education. The integration of AI solutions into existing clinical processes and software systems enables the broad implementation of informed and personalized treatment of GA secondary to AMD.},
}
@article {pmid39082137,
year = {2024},
author = {Shah, R and Vlasak, N and Evans, BJW},
title = {High myopia: Reviews of myopia control strategies and myopia complications.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {44},
number = {6},
pages = {1248-1260},
doi = {10.1111/opo.13366},
pmid = {39082137},
issn = {1475-1313},
mesh = {Humans ; *Myopia/physiopathology/therapy/epidemiology ; *Eyeglasses ; Refraction, Ocular/physiology ; Disease Progression ; Axial Length, Eye ; },
abstract = {BACKGROUND: Myopia and especially high myopia are recognised as major public health concerns. Although the prevalence of high myopia in young children is low, 10-20% of high school children in Asia have high myopia, with many still progressing, and one in three patients with high myopia develop visual impairment with age. Most participants in myopia control studies have low and moderate myopia; relatively little is known about myopia control in high myopia.<br><br>METHOD: Literature searches were undertaken in MEDLINE and EMBASE to identify publications in English, investigating (Aim 1) the efficacy of myopia control strategies (environmental, pharmacological and optical) in high myopia (&#x2264;-6.00 D) and (Aim 2) the complications of high myopia using keywords. Outcomes included change in spherical equivalent refractive error (SE) and/or axial length (AL) to evaluate progression in high myopia.<br><br>RESULTS: Aim 1: Twelve studies were identified that reported the efficacy of optical and pharmacological (none on environmental) interventions on AL and SE for high myopia control. A statistically significant reduction in progression of SE and AL in high myopes was reported with 1% and 0.5% atropine. Defocus Incorporated Multiple Segment spectacle lenses had lower efficacy in slowing high myopia progression compared to moderate and low myopia. Ortho-K lenses were equally effective in reducing myopia progression in low, moderate and high myopia. Aim 2: Myopic patients have an increased risk of myopic macular degeneration, retinal detachment, cataract and glaucoma, with the risk increasing with the level of myopia.<br><br>CONCLUSIONS: High myopia has significant effects on quality of life, risk of pathological complications and vision impairment. Young children, excluding those with some syndromic associations, who are fast progressing moderate and high myopes require early intervention and close monitoring. Further research investigating the efficacy of myopia control strategies in highly myopic patients, both independently and through combination treatments, are necessary.},
}
@article {pmid39081806,
year = {2024},
author = {Liu, G and Tan, M and Liu, R and Lu, X and Jiang, X and Bai, Y and Guo, Z and Lu, F},
title = {Identification of the CDH18 gene associated with age-related macular degeneration using weighted gene co-expression network analysis.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1378340},
pmid = {39081806},
issn = {1664-8021},
abstract = {Purpose: Age-related macular degeneration (AMD) is a chronic and progressive macular degenerative disease that culminates in a gradual deterioration of central vision. Despite its prevalence, the key biomarkers for AMD have not yet been fully elucidated. In this study, we aimed to efficiently identify biomarkers crucial for diagnosing AMD. Methods: Three datasets pertaining to retinal pigment epithelium (RPE)/choroid tissues associated with AMD were selected from the GEO database. The GSE50195 dataset was utilized to conduct weighted gene co-expression network analysis (WGCNA) for identifying module genes linked to AMD. KEGG and GO enrichment analyses were subsequently conducted on these module genes. GSE29801 and GSE135092 datasets were subjected to differential expression analysis to pinpoint the DEGs intersecting with the module genes. Subsequently, wet AMD (wAMD) and dry AMD (dAMD) mouse models were developed, from which RPE/choroid tissues were harvested to validate the hub genes via RT-qPCR and Western blot. Results: Using the WGCNA, we selected the "antiquewhite4" module (r = 0.91 and p = 7e-07), which contains a total of 325 genes. Through the intersection of module genes with DEGs, nine hub genes were identified. Pathways involved in complement and coagulation cascades, ECM-receptor interactions, unsaturated fatty acid biosynthesis, and fatty acid elongation play important roles in AMD. Notably, CDH18 demonstrated notable variance across all three datasets. Post validation using RT-qPCR experiments revealed a significant downregulation of CDH18 in both dAMD and wAMD. EGLN3 was expressed at low levels in wAMD. In dAMD, EYA2, LTB, and PODXL were significantly downregulated, whereas APOC1 was notably upregulated. Western blot confirmed that CDH18 was lowly expressed in dAMD and wAMD mouse models. Conclusion: CDH18 was identified as the key gene involved in the pathogenesis of AMD. An imbalance of the complement and coagulation cascades is a potential mechanism of AMD. This study provides a novel idea for diagnosing and treating AMD in the future.},
}
@article {pmid39080402,
year = {2024},
author = {Kar, SS and Cetin, H and Abraham, J and Srivastava, SK and Madabhushi, A and Ehlers, JP},
title = {Combination of optical coherence tomography-derived shape and texture features are associated with development of sub-foveal geographic atrophy in dry AMD.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {17602},
pmid = {39080402},
issn = {2045-2322},
support = {R43EB028736/EB/NIBIB NIH HHS/United States ; R01CA208236/CA/NCI NIH HHS/United States ; U01 CA239055/CA/NCI NIH HHS/United States ; R01 HL158071/HL/NHLBI NIH HHS/United States ; R01 HL151277/HL/NHLBI NIH HHS/United States ; IP30EY025585//NIH-NEI P30 Core Gran/ ; R01HL151277//National Heart, Lung and Blood Institute/ ; R01CA202752/CA/NCI NIH HHS/United States ; R01 CA216579/CA/NCI NIH HHS/United States ; R01 CA268207/CA/NCI NIH HHS/United States ; IP30EY025585//Unrestricted Grants from The Research to Prevent Blindness, Inc (Cole Eye Institute), Cleveland Eye Bank Foundation awarded to the Cole Eye Institute (Cole Eye)/ ; R01 CA208236/CA/NCI NIH HHS/United States ; R01CA216579/CA/NCI NIH HHS/United States ; R01 CA202752/CA/NCI NIH HHS/United States ; VA Merit Review Award IBX004121A//United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service/ ; C06 RR012463/RR/NCRR NIH HHS/United States ; U01CA248226/CA/NCI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; C06 RR12463-01/RR/NCRR NIH HHS/United States ; R01CA268207A1/CA/NCI NIH HHS/United States ; U01 CA248226/CA/NCI NIH HHS/United States ; I01 BX004121/BX/BLRD VA/United States ; R43 EB028736/EB/NIBIB NIH HHS/United States ; R01HL158071//National Heart, Lung and Blood Institute/ ; R01 CA257612/CA/NCI NIH HHS/United States ; Breast Cancer Research Program (W81XWH-19-1-0668), the Prostate Cancer Research Program (W81XWH-15-1-0558, W81XWH-20-1-0851), the Lung Cancer Research Program (W81XWH-18-1-0440, W81XWH-20-1-0595), the Peer Reviewed Cancer Research Program (W81XWH-18-1-0404, W81XWH-21-1-0345), the Kidney Precision Medicine Project (KPMP) Glue Grant and sponsored research agreements from Bristol Myers-Squibb, Boehri//Office of the Assistant Secretary of Defense for Health Affairs/ ; U54 CA254566/CA/NCI NIH HHS/United States ; R01CA220581/CA/NCI NIH HHS/United States ; U54CA254566/CA/NCI NIH HHS/United States ; U01CA239055/CA/NCI NIH HHS/United States ; R01CA257612/CA/NCI NIH HHS/United States ; R01CA249992/CA/NCI NIH HHS/United States ; R01 CA249992/CA/NCI NIH HHS/United States ; R01 CA220581/CA/NCI NIH HHS/United States ; K23 EY022947/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/diagnostic imaging/pathology ; Female ; Male ; Aged ; Retrospective Studies ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; *Disease Progression ; Fovea Centralis/diagnostic imaging/pathology ; Middle Aged ; Aged, 80 and over ; Macular Degeneration/diagnostic imaging/pathology ; },
abstract = {Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss. Identifying patients with greatest risk of GA progression is important for targeted utilization of emerging therapies. This study aimed to comprehensively evaluate the role of shape-based fractal dimension features (F fd) of sub-retinal pigment epithelium (sub-RPE) compartment and texture-based radiomics features (F t) of Ellipsoid Zone (EZ)-RPE and sub-RPE compartments for risk stratification for subfoveal GA (sfGA) progression. This was a retrospective study of 137 dry AMD subjects with a 5-year follow-up. Based on sfGA status at year 5, eyes were categorized as Progressors and Non-progressors. A total of 15 shape-based F fd of sub-RPE surface and 494 F t from each of sub-RPE and EZ-RPE compartments were extracted from baseline spectral domain-optical coherence tomography scans. The top nine features were identified from F fd and F t feature pool separately using minimum Redundancy maximum Relevance feature selection and used to train a Random Forest (RF) classifier independently using three-fold cross validation on the training set (S t , N = 90) to distinguish between sfGA Progressors and Non-progressors. Combined F fd and F t was also evaluated in predicting risk of sfGA progression. The RF classifier yielded AUC of 0.85, 0.79 and 0.89 on independent test set (S v , N = 47) using F fd , F t , and their combination, respectively. Using combined F fd and F t , the improvement in AUC was statistically significant on S v with p-values of 0.032 and 0.04 compared to using only F fd and only F t , respectively. Combined F fd and F t appears to identify high-risk patients. Our results show that FD and texture features could be potentially used for predicting risk of sfGA progression and future therapeutic response.},
}
@article {pmid39078973,
year = {2024},
author = {Singh, K and Singh, A and Chaudury, P and Jain, D},
title = {Author's Response to Comments on "Efficacy of low-vision devices in the elderly population with age-related macular degeneration".},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {8},
pages = {1226},
pmid = {39078973},
issn = {1998-3689},
mesh = {Humans ; *Macular Degeneration/diagnosis ; *Vision, Low/epidemiology ; Aged ; Visual Acuity/physiology ; },
}
@article {pmid39078959,
year = {2024},
author = {Agarwal, M and Muralidhar, A and Shanmugam, MP and Kothari, A and Dudani, A and Maiti, A and Arora, A and Jayadev, C and Gupta, C and Shroff, D and Chakraborty, D and Pillai, GS and Lahiri, K and Verma, L and Gopalakrishnan, M and Narayanan, R and Mishra, SK and Patil, S and Choudhary, S and Chakraborty, S and Natesh, S and Koundanya, V and Aggarwal, V},
title = {Brolucizumab-associated intraocular inflammation in Indian patients by VRSI study group.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {8},
pages = {1156-1161},
pmid = {39078959},
issn = {1998-3689},
mesh = {Humans ; India/epidemiology ; Retrospective Studies ; *Intravitreal Injections ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Female ; Incidence ; *Antibodies, Monoclonal, Humanized/adverse effects/administration &amp; dosage/therapeutic use ; Middle Aged ; Visual Acuity ; Endophthalmitis/epidemiology/diagnosis ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; Uveitis/drug therapy/diagnosis/epidemiology ; },
abstract = {CONTEXT: Concerns about brolucizumab's (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020.<br><br>PURPOSE: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India.<br><br>SETTINGS AND DESIGN: Retrospective multicentric, survey-based study.<br><br>METHODS: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis.<br><br>RESULTS: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1-65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better.<br><br>CONCLUSIONS: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.},
}
@article {pmid39078733,
year = {2024},
author = {Wu, Z and Pfau, M and Fleckenstein, M and Guymer, RH},
title = {Microperimetry Characteristics of Regions With a Truly Nonresponding Location: Implications for Atrophic Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {44},
pmid = {39078733},
issn = {1552-5783},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Visual Field Tests/methods ; *Visual Fields/physiology ; Female ; Male ; Aged ; *Macular Degeneration/physiopathology/diagnosis ; Geographic Atrophy/physiopathology/diagnosis ; Middle Aged ; Visual Acuity/physiology ; Aged, 80 and over ; },
abstract = {PURPOSE: To understand the microperimetry response characteristics of regions with a truly nonresponding location, which will be useful when considering criteria for end-stage atrophic age-related macular degeneration (AMD).<br><br>METHODS: A simulation model was developed using data from 128 participants with bilateral large drusen at baseline seen over 36&#xa0;months at 6-month intervals. One hundred thousand pairs of real-world microperimetry testing results were simulated separately with and without one truly nonresponding location, where the sensitivity of one randomly selected location for the former group was derived from the distribution of responses from a truly nonresponding location at the optic nerve head from 60 healthy participants.<br><br>RESULTS: Only 60% of the simulated test pairs with a truly nonresponding location had &#x2265;1 location that was <0 decibel (dB) on both tests. In contrast, 91% of the simulated test pairs had &#x2265;1 location that was &#x2264;10&#xa0;dB on both tests, and 87% had &#x2265;1 location that was &#x2264;10&#xa0;dB on both tests and <0&#xa0;dB for one of the tests. Of the simulated test pairs without a truly nonresponding location, there were 0.04%, 1.4%, and 0.4% that met these three above criteria, respectively.<br><br>CONCLUSIONS: Regions with a truly nonresponding test location do not almost always show a repeatable absolute scotoma (<0&#xa0;dB), but instead, much more often a deep visual sensitivity defect (&#x2264;10&#xa0;dB), with or without having an absolute scotoma on one of the tests. These findings are crucial if functional criteria are to be considered as part of a definition of end-stage atrophic AMD.},
}
@article {pmid39076760,
year = {2024},
author = {Chatzimichail, E and Feltgen, N and Motta, L and Empeslidis, T and Konstas, AG and Gatzioufas, Z and Panos, GD},
title = {Transforming the future of ophthalmology: artificial intelligence and robotics' breakthrough role in surgical and medical retina advances: a mini review.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1434241},
pmid = {39076760},
issn = {2296-858X},
abstract = {Over the past decade, artificial intelligence (AI) and its subfields, deep learning and machine learning, have become integral parts of ophthalmology, particularly in the field of ophthalmic imaging. A diverse array of algorithms has emerged to facilitate the automated diagnosis of numerous medical and surgical retinal conditions. The development of these algorithms necessitates extensive training using large datasets of retinal images. This approach has demonstrated a promising impact, especially in increasing accuracy of diagnosis for unspecialized clinicians for various diseases and in the area of telemedicine, where access to ophthalmological care is restricted. In parallel, robotic technology has made significant inroads into the medical field, including ophthalmology. The vast majority of research in the field of robotic surgery has been focused on anterior segment and vitreoretinal surgery. These systems offer potential improvements in accuracy and address issues such as hand tremors. However, widespread adoption faces hurdles, including the substantial costs associated with these systems and the steep learning curve for surgeons. These challenges currently constrain the broader implementation of robotic surgical systems in ophthalmology. This mini review discusses the current research and challenges, underscoring the limited yet growing implementation of AI and robotic systems in the field of retinal conditions.},
}
@article {pmid39074875,
year = {2025},
author = {Bielenberg, DR and D'Amore, PA},
title = {Angiogenesis: Biology and Pathology, Second Edition.},
journal = {Cold Spring Harbor perspectives in medicine},
volume = {15},
number = {3},
pages = {},
pmid = {39074875},
issn = {2157-1422},
mesh = {Animals ; Humans ; Angiogenesis ; *Neovascularization, Pathologic/physiopathology/pathology ; *Neovascularization, Physiologic/physiology ; },
abstract = {During development, the first blood vessels are formed by the de novo assembly of angioblasts, endothelial cell precursors, in a process called vasculogenesis. All subsequent sprouting of blood vessels from pre-existing vessels is termed angiogenesis and is a process that continues throughout our lifespan during physiological processes such as wound healing as well as in number of pathological conditions, such as tumor growth and age-related macular degeneration. The circulatory system pumps blood from the heart out to the organs through arteries and deliveries oxygen and nutrients via capillaries to tissues and cells and returns carbon dioxide and waste products back through veins. Each organ varies in its blood vessel patterning, reflecting specialization to accomplish diverse functions including vascular permeability, filtration, immune trafficking, and hormone regulation. Approximately 90% of the fluid extravasated into the interstitium is recycled back to the circulatory system via the unidirectional lymphatic system. Lymphatic capillaries drain fluid, proteins, and cells from tissues and transport this lymph fluid through collecting lymphatic ducts toward lymph nodes. Eventually lymphatic fluid from the right and left lymphatic ducts joins the subclavian veins and recirculates throughout the circulatory system. These two intricate vascular systems, working in cooperation, help to maintain essential bodily functions such as fluid dynamics, tissue homeostasis, blood pressure, metabolism, and immunity. However, dysfunction of these systems is associated with a host of pathological conditions, including cardiovascular diseases, obesity, retinopathy, hypoxia, necrosis, and vascular malformations.},
}
@article {pmid39073562,
year = {2024},
author = {Fukuda, Y and Notomi, S and Shiose, S and Maehara, Y and Kiyohara, K and Fujiwara, K and Hashimoto, S and Kano, K and Ishikawa, K and Hisatomi, T and Sonoda, KH},
title = {Three-month outcomes of treatment with faricimab or aflibercept for neovascular age-related macular degeneration: a propensity score matching study in a Japanese population.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {12},
pages = {3971-3978},
pmid = {39073562},
issn = {1435-702X},
support = {JP21K09702//Japan Society for the Promotion of Science/ ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; East Asian People ; Fluorescein Angiography ; Follow-Up Studies ; Fundus Oculi ; *Intravitreal Injections ; Japan/epidemiology ; Macula Lutea/pathology ; Propensity Score ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Recombinant Fusion Proteins/administration &amp; dosage ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; },
abstract = {PURPOSE: This study aimed to compare the treatment outcomes of patients with neovascular age-related macular degeneration (nAMD) who initially received faricimab or aflibercept treatment using propensity score matching (PSM) to align patient backgrounds.<br><br>METHODS: Patients with treatment-na&#xef;ve nAMD who received either faricimab or aflibercept for three consecutive monthly injections as the loading phase were enrolled in this study. In the 1:1 PSM, sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and AMD subtypes in the pre-treatment state were selected as covariates. We examined the BCVA, CMT, CCT, and remaining fluid at 1-, 2-, and 3-month after the first injection.<br><br>RESULTS: After PSM, 43 eyes were included in the faricimab and aflibercept group each. Both groups showed significant improvements in BCVA, CMT, and CCT at 1-, 2-, and 3-month after the initial injection compared with baseline. Meanwhile, no significant differences were observed between the two groups at any time point regarding BCVA, CMT, and CCT. At 1-month, 18.6% of patients in the faricimab group and 41.9% in the aflibercept group demonstrated residual subretinal fluid or intraretinal fluid, with a significant difference between the groups (P&#x2009;=&#x2009;0.03).<br><br>CONCLUSION: The BCVA improved after three loading injections of both faricimab and aflibercept. Faricimab may provide a favorable early treatment response in reducing subretinal fluid in a Japanese cohort.},
}
@article {pmid39073397,
year = {2024},
author = {Danzig, CJ and Khanani, AM and Loewenstein, A},
title = {C5 inhibitor avacincaptad pegol treatment for geographic atrophy: A comprehensive review.},
journal = {Immunotherapy},
volume = {16},
number = {12},
pages = {779-790},
pmid = {39073397},
issn = {1750-7448},
support = {//Astellas Pharma Global Development/ ; },
mesh = {Humans ; *Geographic Atrophy/drug therapy ; Complement C5/antagonists &amp; inhibitors ; Clinical Trials as Topic ; Complement Inactivating Agents/therapeutic use ; Animals ; Quality of Life ; },
abstract = {Geographic atrophy (GA) remains a leading cause of central vision loss with no known cure. Until recently, there were no approved treatments for GA, often resulting in poor quality of life for affected patients. GA is characterized by atrophic lesions on the retina that may eventually threaten the fovea. Emerging treatments have demonstrated the ability to reduce the rate of lesion growth, potentially preserving visual function. Avacincaptad pegol (ACP; Astellas Pharma Inc), a complement component 5 inhibitor, is an FDA-approved treatment for GA that has been evaluated in numerous clinical trials. Here we review the current clinical trial landscape of ACP, including critical post hoc analyses that suggest ACP may reduce the risk of severe loss among patients with GA.},
}
@article {pmid39071341,
year = {2024},
author = {Rowe, AA and Reyes, S and Velasquez, MJ and Yee, T and Nettesheim, ER and McDonald, JG and Wert, KJ},
title = {Female sex hormones exacerbate retinal neurodegeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39071341},
issn = {2692-8205},
support = {T32 GM131945/GM/NIGMS NIH HHS/United States ; R21 EY034597/EY/NEI NIH HHS/United States ; P01 HL160487/HL/NHLBI NIH HHS/United States ; P30 EY030413/EY/NEI NIH HHS/United States ; P30 DK127984/DK/NIDDK NIH HHS/United States ; UL1 TR003163/TR/NCATS NIH HHS/United States ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease and macular degeneration represent major sources of human suffering, yet the factors influencing disease severity remain poorly understood. Sex has been implicated as one potential modifying factor. Here, we show that female sex is a risk factor for worsened outcomes in a model of retinal degeneration. Further, we show that this susceptibility is caused by the presence of female-specific circulating sex hormones. The adverse effect of female sex hormones was specific to diseased retinal neurons, and depletion of these hormones ameliorated this phenotypic effect. These findings provide novel insights into the pathogenesis of neurogenerative diseases and how sex hormones can impact the severity of disease. These findings have far-reaching implications for clinical trial design and the use of hormonal therapy in females with certain neurogenerative disorders.},
}
@article {pmid39069106,
year = {2024},
author = {Wong, CYT and Antaki, F and Woodward-Court, P and Ong, AY and Keane, PA},
title = {The role of saliency maps in enhancing ophthalmologists' trust in artificial intelligence models.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {4},
pages = {100087},
doi = {10.1016/j.apjo.2024.100087},
pmid = {39069106},
issn = {2162-0989},
support = {MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Artificial Intelligence ; *Ophthalmologists ; Trust ; Glaucoma/physiopathology ; },
abstract = {PURPOSE: Saliency maps (SM) allow clinicians to better understand the opaque decision-making process in artificial intelligence (AI) models by visualising the important features responsible for predictions. This ultimately improves interpretability and confidence. In this work, we review the use case for SMs, exploring their impact on clinicians' understanding and trust in AI models. We use the following ophthalmic conditions as examples: (1) glaucoma, (2) myopia, (3) age-related macular degeneration, and (4) diabetic retinopathy.<br><br>METHOD: A multi-field search on MEDLINE, Embase, and Web of Science was conducted using specific keywords. Only studies on the use of SMs in glaucoma, myopia, AMD, or DR were considered for inclusion.<br><br>RESULTS: Findings reveal that SMs are often used to validate AI models and advocate for their adoption, potentially leading to biased claims. Overlooking the technical limitations of SMs, and the conductance of superficial assessments of their quality and relevance, was discerned. Uncertainties persist regarding the role of saliency maps in building trust in AI. It is crucial to enhance understanding of SMs' technical constraints and improve evaluation of their quality, impact, and suitability for specific tasks. Establishing a standardised framework for selecting and assessing SMs, as well as exploring their relationship with other reliability sources (e.g. safety and generalisability), is essential for enhancing clinicians' trust in AI.<br><br>CONCLUSION: We conclude that SMs are not beneficial for interpretability and trust-building purposes in their current forms. Instead, SMs may confer benefits to model debugging, model performance enhancement, and hypothesis testing (e.g. novel biomarkers).},
}
@article {pmid39068753,
year = {2024},
author = {Wang, T and Chen, J and Wang, J and Zhang, Y and Mao, W and Yi, Q},
title = {91 Circulating inflammatory proteins and the risk of age-related macular degeneration: A bidirectional Mendelian randomization study.},
journal = {International immunopharmacology},
volume = {139},
number = {},
pages = {112678},
doi = {10.1016/j.intimp.2024.112678},
pmid = {39068753},
issn = {1878-1705},
mesh = {Humans ; *Macular Degeneration/blood/genetics ; *Mendelian Randomization Analysis ; Biomarkers/blood ; Vascular Endothelial Growth Factor A/blood/genetics ; Inflammation Mediators/blood/metabolism ; Polymorphism, Single Nucleotide ; },
abstract = {Previous observational studies have indicated a correlation between circulating inflammatory proteins and age-related macular degeneration (AMD), yet the causal nature of this relationship remains uncertain. This study aims to investigate the causal link between circulating inflammatory proteins and AMD utilizing a bidirectional two-sample Mendelian randomization approach. The findings indicated that elevated levels of four circulating inflammatory proteins, including C-C Motif Chemokine Ligand 11 (CCL11), Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1), TNF Superfamily Member 11 (TRANCE) and Vascular Endothelial Growth Factor A (VEGF-A) lead to the increased risk of AMD, while increased levels of two circulating inflammatory proteins, including Fibroblast Growth Factor 19 (FGF-19) and Interleukin 10 Receptor Subunit Alpha (IL-10RA), resulted in the decreased risk of AMD. Conversely, the results from reverse Mendelian randomization suggested that the presence of AMD lead to the reduction in levels of 15 circulating inflammatory proteins. The findings of this study support the association between elevated levels of circulating inflammatory proteins and the risk of AMD, as well as the potential impact of AMD on reducing circulating inflammatory protein levels. CCL11, SLAMF1, TRANCE and VEGF-A are identified as potential molecular markers in the progression of AMD. These results offer a novel molecular therapeutic target for the prevention and treatment of AMD.},
}
@article {pmid39068248,
year = {2024},
author = {Asani, B and Holmberg, O and Schiefelbein, JB and Hafner, M and Herold, T and Spitzer, H and Siedlecki, J and Kern, C and Kortuem, KU and Frishberg, A and Theis, FJ and Priglinger, SG},
title = {Evaluation of OCT biomarker changes in treatment-naive neovascular AMD using a deep semantic segmentation algorithm.},
journal = {Eye (London, England)},
volume = {38},
number = {16},
pages = {3180-3186},
pmid = {39068248},
issn = {1476-5454},
support = {ZT-I-PF-5-01//Helmholtz Association/ ; 031L0210A//Bundesministerium f&#xfc;r Bildung und Forschung (Federal Ministry of Education and Research)/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Algorithms ; Male ; Aged ; Female ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Intravitreal Injections ; *Biomarkers ; Deep Learning ; Visual Acuity/physiology ; Aged, 80 and over ; Subretinal Fluid/diagnostic imaging ; Ranibizumab/therapeutic use ; Semantics ; },
abstract = {OBJECTIVES: To determine real-life quantitative changes in OCT biomarkers in a large set of treatment naive patients in a real-life setting undergoing anti-VEGF therapy. For this purpose, we devised a novel deep learning based semantic segmentation algorithm providing the first benchmark results for automatic segmentation of 11 OCT features including biomarkers for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Training of a Deep U-net based semantic segmentation ensemble algorithm for state-of-the-art semantic segmentation performance which was used to analyze OCT features prior to, after 3 and 12 months of anti-VEGF therapy.<br><br>RESULTS: High F1 scores of almost 1.0 for neurosensory retina and subretinal fluid on a separate hold-out test set with unseen patients. The algorithm performed worse for subretinal hyperreflective material and fibrovascular PED, on par with drusenoid PED, and better in segmenting fibrosis. In the evaluation of treatment naive OCT scans, significant changes occurred for intraretinal fluid (mean: 0.03&#x2009;&#xb5;m[3] to 0.01&#x2009;&#xb5;m[3], p&#x2009;<&#x2009;0.001), subretinal fluid (0.08&#x2009;&#xb5;m[3] to 0.01&#x2009;&#xb5;m[3], p&#x2009;<&#x2009;0.001), subretinal hyperreflective material (0.02&#x2009;&#xb5;m[3] to 0.01&#x2009;&#xb5;m[3], p&#x2009;<&#x2009;0.001), fibrovascular PED (0.12&#x2009;&#xb5;m[3] to 0.09&#x2009;&#xb5;m[3], p&#x2009;=&#x2009;0.02) and central retinal thickness C0 (225.78&#x2009;&#xb5;m[3] to 169.40&#x2009;&#xb5;m[3]). The amounts of intraretinal fluid, fibrovascular PED, and ERM were predictive of poor outcome.<br><br>CONCLUSIONS: The segmentation algorithm allows efficient volumetric analysis of OCT scans. Anti-VEGF provokes most potent changes in the first 3 months while a gradual loss of RPE hints at a progressing decline of visual acuity. Additional research is required to understand how these accurate OCT predictions can be leveraged for a personalized therapy regimen.},
}
@article {pmid39066843,
year = {2024},
author = {Kickinger, S and Stattin, M and Haas, AM and Ahmed-Balestra, D and Jacob, M and Zehetner, C and Krepler, K and Ansari-Shahrezaei, S},
title = {Comparison between indocyanine green angiography and optical coherence tomography angiography for the detection of nonexudative macular neovascularization.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {12},
pages = {3857-3865},
pmid = {39066843},
issn = {1435-702X},
support = {Topcon Europe Medical//Topcon Europe Medical/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Indocyanine Green/administration &amp; dosage ; *Fluorescein Angiography/methods ; Cross-Sectional Studies ; Female ; *Coloring Agents/administration &amp; dosage/pharmacology ; Male ; Aged ; *Fundus Oculi ; *Wet Macular Degeneration/diagnosis ; Macula Lutea/diagnostic imaging ; Aged, 80 and over ; Visual Acuity ; Retinal Neovascularization/diagnosis ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Middle Aged ; Reproducibility of Results ; },
abstract = {PURPOSE: Patients with unilateral treatment-naïve exudative neovascular age-related macular degeneration (nAMD) were examined for the presence of nonexudative macular neovascularization (neMNV) in their fellow eye using a multimodal imaging approach. This is intended to determine the sensitivity of individual imaging methods, namely, indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA).<br><br>METHODS: In this retrospective cross-sectional study, ICGA images of the nonexudative eye were analyzed for the presence of plaques. SS-OCTA outer retinal segmentations were evaluated for neovascular flow in en-face scans and/or color-coded flow in B-scans. The findings were matched with a double-layer sign (DLS) or pigment epithelium detachment (PED) on conventional OCT.<br><br>RESULTS: In total, neMNV was diagnosed in the fellow eye of 40 of 241 patients (17%) using a multimodal imaging approach employing both ICGA and SS-OCTA. 25 eyes (10%) showed neMNV in both modalities, while 7 (3%) were only detected by ICGA and 8 (3%) by OCTA alone. The sensitivities of ICGA therefore were 80% (32/40) and 83% (33/40) for OCTA. Of the 40 eyes with neMNV, OCT revealed DLS in 25/40 (63%) and PED in 17/40 (43%) of the cases.<br><br>CONCLUSION: None of the modalities alone could detect all neMNV in the partner eye of Caucasians with unilateral treatment-na&#xef;ve exudative nAMD. ICGA and OCTA showed comparable sensitivity. The combination of ICGA, OCTA, and OCT provides the most comprehensive screening for this AMD subtype.},
}
@article {pmid39064598,
year = {2024},
author = {Kin, A and Mizukami, T and Ueno, S and Mishima, S and Shimomura, Y},
title = {Short-Term Comparison of Switching to Brolucizumab or Faricimab from Aflibercept in Neovascular AMD Patients.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {7},
pages = {},
pmid = {39064598},
issn = {1648-9144},
mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Female ; Male ; Aged ; *Intravitreal Injections ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Visual Acuity/drug effects ; Aged, 80 and over ; Treatment Outcome ; Macular Degeneration/drug therapy/complications ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Middle Aged ; },
abstract = {Background and Objectives: In this study, our objective was to assess and compare the changes in visual and structural outcomes among patients with neovascular age-related macular degeneration (nAMD) who were switched from intravitreal aflibercept (IVA) to either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. Materials and Methods: This observational clinical study included 20 eyes of 20 patients switched to brolucizumab and 15 eyes of 14 patients switched to faricimab from aflibercept in eyes with nAMD. We measured the structural outcome (central macular thickness (CMT)) and the visual outcome (best-corrected visual acuity (BCVA); logMAR) as follows: just before the most recent IVA injection (B0), one month after the most recent IVA injection (B1), just before the first IVBr or IVF injection (A0), one month after (A1) and three months after (A3) the first IVBr or IVF injection. Results: BCVA showed significant improvement at A1 (0.25 ± 0.34) and at A3 (0.19 ± 0.24) compared to A0 (0.38 ± 0.35) in the IVBr group (p = 0.0156, p = 0.0166, respectively). CMT (μm) was significantly thinner at A1 (IVBr: 240.55 ± 51.82, IVF: 234.91 ± 47.29) and at A3 (IVBr: 243.21 ± 76.15, IVF: 250.50 ± 72.61) compared to at A0 (IVBr: 303.55 ± 79.18, IVF: 270.33 ± 77.62) in the IVBr group (A1: p = 0.0093, A3: p = 0.0026) and in the IVF group (A1: p = 0.0161, A3: p = 0.0093). There was no significant difference in BCVA and CMT improvement observed between two groups at any time point (p > 0.05 for all). Conclusions: Switching from aflibercept to either brolucizumab or faricimab has a significant anatomical effect in eyes with nAMD and both treatments appear to be effective short-term treatment options. There is a trend towards greater visual improvements and reductions in CMT with brolucizumab.},
}
@article {pmid39064267,
year = {2024},
author = {Śpiewak, D and Drzyzga, &#x141; and Dorecka, M and Wyględowska-Promieńska, D},
title = {Summary of the Therapeutic Options for Patients with Dry and Neovascular AMD.},
journal = {Journal of clinical medicine},
volume = {13},
number = {14},
pages = {},
pmid = {39064267},
issn = {2077-0383},
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have been identified, which can be divided into non-modifiable, including genetic factors, age, and sex, and modifiable or environmental factors, such as smoking, poor diet, and hypertension. Early stages of age-related macular degeneration are characterized by fundus drusen and abnormalities in the retinal pigment epithelium. In late stages, geographic atrophy and choroidal neovascularization (CNV) are observed. The treatment of AMD, especially its advanced forms, is very challenging. Intensive research has made it possible to treat advanced stages of the dry form of AMD with pegcetacoplan and avacincaptad pegol, new drugs approved for use in the US. Pegcetacoplan targets the C3 and avacincaptad pegol targets the C5, the pivotal proteins of the complement cascade. The drugs are administered by intravitreal injection. The gold standard for neovascular AMD (nAMD) consists of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. Treatment can be administered according to the fixed, pro-re-nata, and treat-and-extend regimens. The latter seems to have the best effect on improving visual acuity (VA) and the maximum therapeutic benefit. The search continues for the best ways to deliver intravitreal drugs. Current methods include sustained-release implants and hydrogel platforms for drug release, while the most promising future pathways for treating dry and nAMD are stem cell and gene therapy.},
}
@article {pmid39064170,
year = {2024},
author = {Saßmannshausen, M and Sautbaeva, L and von der Emde, LA and Vaisband, M and Sloan, KR and Hasenauer, J and Holz, FG and Ach, T},
title = {Retro Mode Imaging for Detection and Quantification of Sub-RPE Drusen and Subretinal Drusenoid Deposits in Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {14},
pages = {},
pmid = {39064170},
issn = {2077-0383},
support = {NA//Nidek (Japan)/ ; },
abstract = {Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face drusen and SDD area detection in eyes with non-exudative AMD using conventional imaging modalities versus Retro mode imaging. We also quantitatively assess the topographic distribution of drusen and SDDs. Methods: In total, 120 eyes of 90 subjects (mean age ± standard deviation = 74.6 ± 8.6 years) were included. Coherent en-face drusen and SDD areas were measured via near-infrared reflectance, green (G-) and blue (B-) fundus autofluorescence (AF), and Retro mode imaging. Drusen phenotypes were classified by correlating en-face drusen areas using structural high-resolution spectral domain optical coherence tomography. The topographic distribution of drusen was analyzed according to a modified ETDRS (Early Treatment of Diabetic Retinopathy Study) grid. Intraclass correlation coefficient (ICC) analysis was applied to determine the inter-reader agreement in the SDD en-face area assessment. Results: The largest coherent en-face drusen area was found using Retro mode imaging with a mean area of 105.2 ± 45.9 mm[2] (deviated left mode (DL)) and 105.4 ± 45.5 mm[2] (deviated right mode (DR)). The smallest en-face drusen areas were determined by GAF (50.9 ± 42.6 mm[2]) and BAF imaging (49.1 ± 42.9 mm[2]) (p < 0.001). The inter-reader agreement for SDD en-face areas ranged from 0.93 (DR) to 0.70 (BAF). The topographic analysis revealed the highest number of SDDs in the superior peripheral retina, whereas sub-retinal pigment epithelium drusen were mostly found in the perifoveal retina. Retro mode imaging further enabled the detection of the earliest SDD stages. Conclusions: Retro mode imaging allows for a detailed detection of drusen phenotypes. While hundreds/thousands of SDDs can be present in one eye, the impact of SDD number or volume on AMD progression still needs to be evaluated. However, this new imaging modality can add important knowledge on drusen development and the pathophysiology of AMD.},
}
@article {pmid39062975,
year = {2024},
author = {Bammidi, S and Koontz, V and Gautam, P and Hose, S and Sinha, D and Ghosh, S},
title = {Neutrophils in Ocular Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {14},
pages = {},
pmid = {39062975},
issn = {1422-0067},
support = {1R01EY032516-02A1/NH/NIH HHS/United States ; N/A//BrightFocus Foundation Postdoctoral Fellowship on Macular Degeneration/ ; Unrestricted funds to University of Pittsburgh Department of Ophthalmology//Research to Prevent Blindness/ ; Jennifer Salvitti Davis, M.D. Chair Professorship in Ophthalmology to Debasish Sinha//University of Pittsburgh/ ; R01 EY032516/EY/NEI NIH HHS/United States ; Start-up funding//University of Pittsburgh/ ; 1R01EY031594-03A1/NH/NIH HHS/United States ; 1K99EY033421-01A1/NH/NIH HHS/United States ; P30EY08098/EY/NEI NIH HHS/United States ; N/A//Edward N. and Della L. Thome Memorial Foundation Awards Program in Age-Related Macular Degeneration Research/ ; },
mesh = {Humans ; *Neutrophils/immunology/metabolism ; *Eye Diseases/immunology/therapy ; Animals ; Extracellular Traps/metabolism/immunology ; Macular Degeneration/immunology/pathology/metabolism ; },
abstract = {Neutrophils, traditionally viewed as first responders to infection or tissue damage, exhibit dynamic and diverse roles in ocular health and disease. This review elaborates on previous findings that showed how neutrophils contribute to ocular diseases. In ocular infections, neutrophils play a pivotal role in host defense by orchestrating inflammatory responses to combat pathogens. Furthermore, in optic nerve neuropathies and retinal degenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR), neutrophils are implicated in neuroinflammation and tissue damage owing to their ability to undergo neutrophil extracellular trap formation (NETosis) and secretion of inflammatory molecules. Targeting neutrophil-dependent processes holds promise as a therapeutic strategy, offering potential avenues for intervention in ocular infections, cancers, and retinal degenerative diseases. Understanding the multifaceted roles of neutrophils in ocular diseases is crucial for developing targeted therapies to improve patient outcomes.},
}
@article {pmid39062844,
year = {2024},
author = {Bas, TG},
title = {Bioactivity and Bioavailability of Carotenoids Applied in Human Health: Technological Advances and Innovation.},
journal = {International journal of molecular sciences},
volume = {25},
number = {14},
pages = {},
pmid = {39062844},
issn = {1422-0067},
mesh = {*Carotenoids/chemistry/pharmacokinetics ; Humans ; *Biological Availability ; Cardiovascular Diseases/drug therapy ; Neoplasms/drug therapy/metabolism ; Animals ; Macular Degeneration/drug therapy/metabolism ; },
abstract = {This article presents a groundbreaking perspective on carotenoids, focusing on their innovative applications and transformative potential in human health and medicine. Research jointly delves deeper into the bioactivity and bioavailability of carotenoids, revealing therapeutic uses and technological advances that have the potential to revolutionize medical treatments. We explore pioneering therapeutic applications in which carotenoids are used to treat chronic diseases such as cancer, cardiovascular disease, and age-related macular degeneration, offering novel protective mechanisms and innovative therapeutic benefits. Our study also shows cutting-edge technological innovations in carotenoid extraction and bioavailability, including the development of supramolecular carriers and advanced nanotechnology, which dramatically improve the absorption and efficacy of these compounds. These technological advances not only ensure consistent quality but also tailor carotenoid therapies to each patient's health needs, paving the way for personalized medicine. By integrating the latest scientific discoveries and innovative techniques, this research provides a prospective perspective on the clinical applications of carotenoids, establishing a new benchmark for future studies in this field. Our findings underscore the importance of optimizing carotenoid extraction, administration, bioactivity, and bioavailability methods to develop more effective, targeted, and personalized treatments, thus offering visionary insight into their potential in modern medical practices.},
}
@article {pmid39062152,
year = {2024},
author = {Kulbay, M and Wu, KY and Nirwal, GK and Bélanger, P and Tran, SD},
title = {The Role of Reactive Oxygen Species in Age-Related Macular Degeneration: A Comprehensive Review of Antioxidant Therapies.},
journal = {Biomedicines},
volume = {12},
number = {7},
pages = {},
pmid = {39062152},
issn = {2227-9059},
abstract = {This review article delves into the intricate roles of reactive oxygen species (ROS) in the pathogenesis of age-related macular degeneration (AMD). It presents a detailed analysis of the oxidative stress mechanisms that contribute to the development and progression of these diseases. The review systematically explores the dual nature of ROS in ocular physiology and pathology, underscoring their essential roles in cellular signaling and detrimental effects when in excess. In the context of AMD, the focus is on the oxidative impairment in the retinal pigment epithelium and Bruch's membrane, culminating in the deterioration of macular health. Central to this review is the evaluation of various antioxidant strategies in the prevention and management of AMD. It encompasses a wide spectrum of antioxidants, ranging from dietary nutrients like vitamins C and E, lutein, and zeaxanthin to pharmacological agents with antioxidative properties. The review also addresses novel therapeutic approaches, including gene therapy and nanotechnology-based delivery systems, aiming to enhance antioxidant defense mechanisms in ocular tissues. The article concludes by synthesizing current research findings, clinical trial data, and meta-analyses to provide evidence-based recommendations. It underscores the need for further research to optimize antioxidant therapies, considering individual patient factors and disease stages. This comprehensive review thus serves as a valuable resource for clinicians, researchers, and healthcare professionals in ophthalmology, offering insights into the potential of antioxidants in mitigating the burden of AMD.},
}
@article {pmid39062052,
year = {2024},
author = {Bhumika, and Bora, NS and Bora, PS},
title = {Genetic Insights into Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {12},
number = {7},
pages = {},
pmid = {39062052},
issn = {2227-9059},
abstract = {One of the major causes of vision impairment among elderly people in developed nations is age-related macular degeneration (AMD). The distinctive features of AMD are the accumulation of extracellular deposits called drusen and the gradual deterioration of photoreceptors and nearby tissues in the macula. AMD is a complex and multifaceted disease influenced by several factors such as aging, environmental risk factors, and a person's genetic susceptibility to the condition. The interaction among these factors leads to the initiation and advancement of AMD, where genetic predisposition plays a crucial role. With the advent of high-throughput genotyping technologies, many novel genetic loci associated with AMD have been identified, enhancing our knowledge of its genetic architecture. The common genetic variants linked to AMD are found on chromosome 1q32 (in the complement factor H gene) and 10q26 (age-related maculopathy susceptibility 2 and high-temperature requirement A serine peptidase 1 genes) loci, along with several other risk variants. This review summarizes the common genetic variants of complement pathways, lipid metabolism, and extracellular matrix proteins associated with AMD risk, highlighting the intricate pathways contributing to AMD pathogenesis. Knowledge of the genetic underpinnings of AMD will allow for the future development of personalized diagnostics and targeted therapeutic interventions, paving the way for more effective management of AMD and improved outcomes for affected individuals.},
}
@article {pmid39061982,
year = {2024},
author = {Godaert, L and Dramé, M},
title = {Efficacy of Photobiomodulation Therapy in Older Adults: A Systematic Review.},
journal = {Biomedicines},
volume = {12},
number = {7},
pages = {},
pmid = {39061982},
issn = {2227-9059},
abstract = {BACKGROUND: The aim was to determine whether there is any available evidence on the efficacy of photobiomodulation therapy (PBMT) in older adults.<br><br>METHODS: A literature search was performed including all articles published up to February 2024. Studies reporting data on PBMT in older adults were included. This study was registered with PROSPERO.<br><br>RESULTS: In total, 406 studies were identified. After eliminating duplicates and irrelevant studies, 10 records were included in the final review. In all included studies, the protocols used to deliver PBMT were different in terms of type of device, wavelength, irradiation duration, and pulse frequency. In neurodegenerative diseases, two studies reported non-significant results, while two studies reported efficacy of PBMT. In wounds and ulcers, two out of three studies reported efficacy of PBMT. In macular degeneration, one study reported efficacy of PBMT. One study on hyposalivation reported efficacy of PBMT.<br><br>CONCLUSION: PBMT appears to be a promising complementary treatment. All studies reported good compliance and safety throughout the treatment. In the future, it will be essential to harmonize PBMT parameters. Further studies are warranted to define the best indications, the most effective protocols, and the right population to target for use in routine practice.},
}
@article {pmid39061793,
year = {2024},
author = {Abd El-Khalek, AA and Balaha, HM and Sewelam, A and Ghazal, M and Khalil, AT and Abo-Elsoud, MEA and El-Baz, A},
title = {A Comprehensive Review of AI Diagnosis Strategies for Age-Related Macular Degeneration (AMD).},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {7},
pages = {},
pmid = {39061793},
issn = {2306-5354},
abstract = {The rapid advancement of computational infrastructure has led to unprecedented growth in machine learning, deep learning, and computer vision, fundamentally transforming the analysis of retinal images. By utilizing a wide array of visual cues extracted from retinal fundus images, sophisticated artificial intelligence models have been developed to diagnose various retinal disorders. This paper concentrates on the detection of Age-Related Macular Degeneration (AMD), a significant retinal condition, by offering an exhaustive examination of recent machine learning and deep learning methodologies. Additionally, it discusses potential obstacles and constraints associated with implementing this technology in the field of ophthalmology. Through a systematic review, this research aims to assess the efficacy of machine learning and deep learning techniques in discerning AMD from different modalities as they have shown promise in the field of AMD and retinal disorders diagnosis. Organized around prevalent datasets and imaging techniques, the paper initially outlines assessment criteria, image preprocessing methodologies, and learning frameworks before conducting a thorough investigation of diverse approaches for AMD detection. Drawing insights from the analysis of more than 30 selected studies, the conclusion underscores current research trajectories, major challenges, and future prospects in AMD diagnosis, providing a valuable resource for both scholars and practitioners in the domain.},
}
@article {pmid39061606,
year = {2024},
author = {Muntean, GA and Marginean, A and Groza, A and Damian, I and Roman, SA and Hapca, MC and Sere, AM and Mănoiu, RM and Muntean, MV and Nicoară, SD},
title = {A Qualitative Evaluation of ChatGPT4 and PaLM2's Response to Patient's Questions Regarding Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {14},
pages = {},
pmid = {39061606},
issn = {2075-4418},
support = {PN-III-P2-2.1-PED-2021-2709//Executive Agency for Higher Education, Research, Development and Innovation Funding (UEFISCDI)/ ; },
abstract = {Patient compliance in chronic illnesses is essential for disease management. This also applies to age-related macular degeneration (AMD), a chronic acquired retinal degeneration that needs constant monitoring and patient cooperation. Therefore, patients with AMD can benefit by being properly informed about their disease, regardless of the condition's stage. Information is essential in keeping them compliant with lifestyle changes, regular monitoring, and treatment. Large language models have shown potential in numerous fields, including medicine, with remarkable use cases. In this paper, we wanted to assess the capacity of two large language models (LLMs), ChatGPT4 and PaLM2, to offer advice to questions frequently asked by patients with AMD. After searching on AMD-patient-dedicated websites for frequently asked questions, we curated and selected a number of 143 questions. The questions were then transformed into scenarios that were answered by ChatGPT4, PaLM2, and three ophthalmologists. Afterwards, the answers provided by the two LLMs to a set of 133 questions were evaluated by two ophthalmologists, who graded each answer on a five-point Likert scale. The models were evaluated based on six qualitative criteria: (C1) reflects clinical and scientific consensus, (C2) likelihood of possible harm, (C3) evidence of correct reasoning, (C4) evidence of correct comprehension, (C5) evidence of correct retrieval, and (C6) missing content. Out of 133 questions, ChatGPT4 received a score of five from both reviewers to 118 questions (88.72%) for C1, to 130 (97.74%) for C2, to 131 (98.50%) for C3, to 133 (100%) for C4, to 132 (99.25%) for C5, and to 122 (91.73%) for C6, while PaLM2 to 81 questions (60.90%) for C1, to 114 (85.71%) for C2, to 115 (86.47%) for C3, to 124 (93.23%) for C4, to 113 (84.97%) for C5, and to 93 (69.92%) for C6. Despite the overall high performance, there were answers that are incomplete or inaccurate, and the paper explores the type of errors produced by these LLMs. Our study reveals that ChatGPT4 and PaLM2 are valuable instruments for patient information and education; however, since there are still some limitations to these models, for proper information, they should be used in addition to the advice provided by the physicians.},
}
@article {pmid39060633,
year = {2024},
author = {Linder, M and Bennink, L and Foxton, RH and Kirkness, M and Westenskow, PD},
title = {In vivo monitoring of active subretinal fibrosis in mice using collagen hybridizing peptides.},
journal = {Lab animal},
volume = {53},
number = {8},
pages = {196-204},
pmid = {39060633},
issn = {1548-4475},
mesh = {Animals ; Mice ; *Fibrosis ; *Collagen/metabolism ; Peptides ; Disease Models, Animal ; Choroidal Neovascularization/pathology ; Mice, Inbred C57BL ; Retina/pathology ; Macular Degeneration/pathology ; Retinal Pigment Epithelium/pathology ; },
abstract = {Subretinal fibrosis is associated with worse visual outcomes in patients with neovascular age-related macular degeneration. As there is a lack of optimal biomarkers and no method that directly detects collagen in the back of the eye, novel tools that monitor fibrosis-related changes in neovascular age-related macular degeneration are needed. Here, using two mouse models (the laser-induced choroidal neovascularization model, and the JR5558 mouse presenting with spontaneous subretinal neovascularization with fibrosis), we imaged active fibrotic lesions using fluorescently labeled collagen hybridizing peptides (CHPs), short peptides that bind to single α-chain collagen structures during collagen remodeling. JR5558 retinal pigment epithelium/choroid flat mounts showed CHP co-staining with fibrosis and epithelial mesenchymal transition-related markers; additionally, CHP histopathology staining correlated with in vivo CHP imaging. After laser-induced choroidal neovascularization, in vivo CHP binding correlated with laser intensity, histopathology CHP and fibronectin staining. Laser-induced choroidal neovascularization showed decreased CHP intensity over time in healing/regressing versus active scars in vivo, whereas increased CHP binding correlated with elevated fibrosis in JR5558 mouse eyes with age. In bispecific angiopoietin 2/vascular endothelial growth factor antibody-treated JR5558 mice, CHPs detected significantly decreased collagen remodeling versus immunoglobulin G control. These results demonstrate the first use of CHPs to directly image remodeling collagen in the eye and as a potential clinical optical biomarker of active subretinal fibrosis associated with ocular neovascularization.},
}
@article {pmid39056810,
year = {2024},
author = {Lee, DH and Han, JW and Park, H and Hong, SJ and Kim, CS and Kim, YS and Lee, IS and Kim, GJ},
title = {Achyranthis radix Extract Enhances Antioxidant Effect of Placenta-Derived Mesenchymal Stem Cell on Injured Human Ocular Cells.},
journal = {Cells},
volume = {13},
number = {14},
pages = {},
pmid = {39056810},
issn = {2073-4409},
support = {1425178959//Industry-Academia-Research Institute (IAR) Collabo R&amp;D Fund Grant funded by Korea Government/ ; N/A//PLABiologics Co., Ltd./ ; },
mesh = {Humans ; *Mesenchymal Stem Cells/drug effects/metabolism ; *Antioxidants/pharmacology ; *Plant Extracts/pharmacology ; Female ; *Placenta/metabolism/drug effects ; Pregnancy ; Achyranthes/chemistry ; Retinal Pigment Epithelium/drug effects/metabolism/cytology ; Cell Proliferation/drug effects ; Cell Line ; },
abstract = {Age-related ocular diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy are major causes of irreversible vision impairment in the elderly. Conventional treatments focus on symptom relief and disease slowdown, often involving surgery, but fall short of providing a cure, leading to substantial vision loss. Regenerative medicine, particularly mesenchymal stem cells (MSCs), holds promise for ocular disease treatment. This study investigates the synergistic potential of combining placenta-derived MSCs (PD-MSCs) with Achyranthis radix extract (ARE) from Achyranthes japonica to enhance therapeutic outcomes. In a 24-h treatment, ARE significantly increased the proliferative capacity of PD-MSCs and delayed their senescence (* p < 0.05). ARE also enhanced antioxidant capabilities and increased the expression of regeneration-associated genes in an in vitro injured model using chemical damages on human retinal pigment epithelial cell line (ARPE-19) (* p < 0.05). These results suggest that ARE-primed PD-MSC have the capability to enhance the activation of genes associated with regeneration in the injured eye via increasing antioxidant properties. Taken together, these findings support the conclusion that ARE-primed PD-MSC may serve as an enhanced source for stem cell-based therapy in ocular diseases.},
}
@article {pmid39056591,
year = {2024},
author = {Lortlar Ünlü, N and Bakhshpour-Yucel, M and Chiodi, E and Diken-Gür, S and Emre, S and Ünlü, MS},
title = {Characterization of Receptor Binding Affinity for Vascular Endothelial Growth Factor with Interferometric Imaging Sensor.},
journal = {Biosensors},
volume = {14},
number = {7},
pages = {},
pmid = {39056591},
issn = {2079-6374},
mesh = {*Vascular Endothelial Growth Factor A/metabolism ; Humans ; *Interferometry ; Bevacizumab ; Receptors, Vascular Endothelial Growth Factor ; Biosensing Techniques ; Protein Binding ; Recombinant Fusion Proteins ; Macular Degeneration/metabolism ; },
abstract = {Wet Age-related macular degeneration (AMD) is the leading cause of vision loss in industrialized nations, often resulting in blindness. Biologics, therapeutic agents derived from biological sources, have been effective in AMD, albeit at a high cost. Due to the high cost of AMD treatment, it is critical to determine the binding affinity of biologics to ensure their efficacy and make quantitative comparisons between different drugs. This study evaluates the in vitro VEGF binding affinity of two drugs used for treating wet AMD, monoclonal antibody-based bevacizumab and fusion protein-based aflibercept, performing quantitative binding measurements on an Interferometric Reflectance Imaging Sensor (IRIS) system. Both biologics can inhibit Vascular Endothelial Growth Factor (VEGF). For comparison, the therapeutic molecules were immobilized on to the same support in a microarray format, and their real-time binding interactions with recombinant human VEGF (rhVEGF) were measured using an IRIS. The results indicated that aflibercept exhibited a higher binding affinity to VEGF than bevacizumab, consistent with previous studies using ELISA and SPR. The IRIS system's innovative and cost-effective features, such as silicon-based semiconductor chips for enhanced signal detection and multiplexed analysis capability, offer new prospects in sensor technologies. These attributes make IRISs a promising tool for future applications in the development of therapeutic agents, specifically biologics.},
}
@article {pmid39051044,
year = {2024},
author = {Nusinovici, S and Zhou, L and Wang, X and Tham, YC and Wang, X and Wong, TY and Chakravarthy, U and Cheng, CY},
title = {Contributions of Lipid-Related Metabolites and Complement Proteins to Early and Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {5},
pages = {100538},
pmid = {39051044},
issn = {2666-9145},
abstract = {OBJECTIVE: Our objective was to determine the effects of lipids and complement proteins on early and intermediate age-related macular degeneration (AMD) stages using machine learning models by integrating metabolomics and proteomic data.<br><br>DESIGN: Nested case-control study.<br><br>SUBJECTS AND CONTROLS: The analyses were performed in a subset of the Singapore Indian Chinese Cohort (SICC) Eye Study. Among the 6753 participants, we randomly selected 155 Indian and 155 Chinese cases of AMD and matched them with 310 controls on age, sex, and ethnicity.<br><br>METHODS: We measured 35 complement proteins and 56 lipids using mass spectrometry and nuclear magnetic resonance, respectively. We first selected the most contributing lipids and complement proteins to early and intermediate AMD using random forest models. Then, we estimated their effects using a multinomial model adjusted for potential confounders.<br><br>MAIN OUTCOME MEASURES: Age-related macular degeneration was classified using the Beckman classification system.<br><br>RESULTS: Among the 310 individuals with AMD, 166 (53.5%) had early AMD, and 144 (46.5%) had intermediate AMD. First, high-density lipoprotein (HDL) particle diameter was positively associated with both early and intermediate AMD (odds ratio [OR]early&#xa0;= 1.69; 95% confidence interval [CI],1.11-2.55 and ORintermediate&#xa0;= 1.72; 95% CI, 1.11-2.66 per 1-standard deviation increase in HDL diameter). Second, complement protein 2 (C2), complement C1 inhibitor (IC1), complement protein 6 (C6), complement protein 1QC (C1QC) and complement factor H-related protein 1 (FHR1), were associated with AMD. C2 was positively associated with both early and intermediate AMD (ORearly&#xa0;= 1.58; 95% CI, 1.08-2.30 and ORintermediate&#xa0;= 1.56; 95% CI, 1.04-2.34). C6 was positively (ORearly&#xa0;= 1.41; 95% CI, 1.03-1.93) associated with early AMD. However, IC1 was negatively associated with early AMD (ORearly&#xa0;= 0.62; 95% CI, 0.38-0.99), whereas C1QC (ORintermediate&#xa0;= 0.63; 95% CI, 0.42-0.93) and FHR1 (ORintermediate&#xa0;= 0.73; 95% CI, 0.54-0.98) were both negatively associated with intermediate AMD.<br><br>CONCLUSIONS: Although both HDL diameter and C2 levels show associations with both early and intermediate AMD, dysregulations of IC1, C6, C1QC, and FHR1 are only observed at specific stages of AMD. These findings underscore the complexity of complement system dysregulation in AMD, which appears to vary depending on the disease severity.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid39049295,
year = {2024},
author = {O'Connor, S and Treanor, C and Ward, E and Wickens, R and O'Connell, A and Culliford, L and Rogers, C and Gidman, E and Peto, T and Knox, P and Burton, B and Lotery, A and Sivaprasad, S and Reeves, B and Hogg, R and Donnelly, M},
title = {Acceptability of Home Monitoring for Neovascular Age-Related Macular Degeneration Reactivation: A Qualitative Study.},
journal = {Studies in health technology and informatics},
volume = {315},
number = {},
pages = {425-429},
doi = {10.3233/SHTI240182},
pmid = {39049295},
issn = {1879-8365},
mesh = {Aged ; Aged, 80 and over ; Female ; Digital Technology ; Family ; Health Education ; Health Personnel ; Interviews as Topic ; *Macular Degeneration/diagnosis ; *Monitoring, Ambulatory/methods ; *Patient Acceptance of Health Care ; Patient Satisfaction ; Patients ; *Qualitative Research ; Recurrence ; *Home Care Services ; Humans ; },
abstract = {This study formed part of a diagnostic test accuracy study to quantify the ability of three index home monitoring (HM) tests (one paper-based and two digital tests) to identify reactivation in Neovascular age-related macular degeneration (nAMD). The aim of the study was to investigate views about acceptability and explore adherence to weekly HM. Semi-structured interviews were held with 98 patients, family members, and healthcare professionals. A thematic approach was used which was informed by theories of technology acceptance. Various factors influenced acceptability including a patient's understanding about the purpose of monitoring. Training and ongoing support were regarded as essential for overcoming unfamiliarity with digital technology. Findings have implications for implementation of digital HM in the care of older people with nAMD and other long-term conditions.},
}
@article {pmid39047907,
year = {2024},
author = {Grenell, A and Singh, C and Raju, M and Wolk, A and Dalvi, S and Jang, GF and Crabb, JS and Hershberger, CE and Manian, KV and Hernandez, K and Crabb, JW and Singh, R and Du, J and Anand-Apte, B},
title = {Tissue Inhibitor of Metalloproteinase 3 (TIMP3) mutations increase glycolytic activity and dysregulate glutamine metabolism in RPE cells.},
journal = {Molecular metabolism},
volume = {88},
number = {},
pages = {101995},
pmid = {39047907},
issn = {2212-8778},
support = {R01 EY034364/EY/NEI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; R01 EY027083/EY/NEI NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; R01 EY031324/EY/NEI NIH HHS/United States ; R01 EY032462/EY/NEI NIH HHS/United States ; R01 EY031720/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; Cell Line ; *Glutamine/metabolism ; *Glycolysis ; Macular Degeneration/metabolism/genetics ; *Mutation ; Proteomics/methods ; *Retinal Pigment Epithelium/metabolism ; *Tissue Inhibitor of Metalloproteinase-3/metabolism/genetics ; },
abstract = {OBJECTIVES: Mutations in Tissue Inhibitor of Metalloproteinases 3 (TIMP3) cause Sorsby's Fundus Dystrophy (SFD), a dominantly inherited, rare form of macular degeneration that results in vision loss. TIMP3 is synthesized primarily by retinal pigment epithelial (RPE) cells, which constitute the outer blood-retinal barrier. One major function of RPE is the synthesis and transport of vital nutrients, such as glucose, to the retina. Recently, metabolic dysfunction in RPE cells has emerged as an important contributing factor in retinal degenerations. We set out to determine if RPE metabolic dysfunction was contributing to SFD pathogenesis.<br><br>METHODS: Quantitative proteomics was conducted on RPE of mice expressing the S179C variant of TIMP3, known to be causative of SFD in humans. Proteins found to be differentially expressed (P&#xa0;<&#xa0;0.05) were analyzed using statistical overrepresentation analysis to determine enriched pathways, processes, and protein classes using g:profiler and PANTHER Gene Ontology. We examined the effects of mutant TIMP3 on RPE metabolism using human ARPE-19 cells expressing mutant S179C TIMP3 and patient-derived induced pluripotent stem cell-derived RPE (iRPE) carrying the S204C TIMP3 mutation. RPE metabolism was directly probed using isotopic tracing coupled with GC/MS analysis. Steady state [U-[13]C6] glucose isotopic tracing was preliminarily conducted on S179C ARPE-19 followed by [U-[13]C6] glucose and [U-[13]C5] glutamine isotopic tracing in SFD iRPE cells.<br><br>RESULTS: Quantitative proteomics and enrichment analysis conducted on RPE of mice expressing mutant S179C TIMP3 identified differentially expressed proteins that were enriched for metabolism-related pathways and processes. Notably these results highlighted dysregulated glycolysis and glucose metabolism. Stable isotope tracing experiments with [U-[13]C6] glucose demonstrated enhanced glucose utilization and glycolytic activity in S179C TIMP3 APRE-19 cells. Similarly, [U-[13]C6] glucose tracing in SFD iRPE revealed increased glucose contribution to glycolysis and the TCA cycle. Additionally, [U-[13]C5] glutamine tracing found evidence of altered malic enzyme activity.<br><br>CONCLUSIONS: This study provides important information on the dysregulation of RPE glucose metabolism in SFD and implicates a potential commonality with other retinal degenerative diseases, emphasizing RPE cellular metabolism as a therapeutic target.},
}
@article {pmid39047706,
year = {2024},
author = {Chan, EJ and Anders, P and Garobbio, SA and Hall, U and Gabrani, C and Pfau, K and Camenzind Zuche, H and Futterknecht, S and Pfau, M and Herzog, M and Traber, GL and Scholl, HPN},
title = {Retinal Sensitivity in Macular Subfields and Their Association with Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {458-469},
doi = {10.1159/000540312},
pmid = {39047706},
issn = {1423-0259},
mesh = {Humans ; *Contrast Sensitivity/physiology ; Female ; Male ; Prospective Studies ; Aged ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; *Visual Field Tests ; *Retina/physiopathology ; *Macular Degeneration/physiopathology/diagnosis ; Middle Aged ; *Macula Lutea/physiopathology ; Visual Fields/physiology ; Follow-Up Studies ; Aged, 80 and over ; },
abstract = {INTRODUCTION: The objective of this study was to evaluate retinal sensitivity in subfields and its association with the novel quantitative contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls.<br><br>METHODS: In this prospective longitudinal study, retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA, USA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest.<br><br>RESULTS: 92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p < 0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD, significant differences were found between central and peripheral subfields (p < 0.001) and specific subfields (p < 0.05) and finally for iAMD between specific quadrants (p < 0.05) and specific squares (p < 0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function, contrast acuity and for the contrast sensitivity at specific spatial frequencies.<br><br>CONCLUSIONS: This study showed significant differences in the evaluated retinal sensitivity subfields, providing localized natural history data for retinal sensitivity in healthy controls and patients with eAMD and iAMD.},
}
@article {pmid39047196,
year = {2024},
author = {Frank, S and Reiter, GS and Leingang, O and Fuchs, P and Coulibaly, LM and Mares, V and Bogunovic, H and Schmidt-Erfurth, U},
title = {ADVANCES IN PHOTORECEPTOR AND RETINAL PIGMENT EPITHELIUM QUANTIFICATIONS IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION: High-Res Versus Standard SPECTRALIS Optical Coherence Tomography.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {8},
pages = {1351-1359},
pmid = {39047196},
issn = {1539-2864},
support = {//Christian Doppler Forschungsgesellschaft, Bundesministerium f&#xc3;&#xbc;r Digitalisierung und Wirtschaftsstandort/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Female ; Male ; Aged ; Aged, 80 and over ; Photoreceptor Cells, Vertebrate/pathology ; Visual Acuity/physiology ; Retinal Drusen/diagnosis/diagnostic imaging ; Macular Degeneration/diagnosis/physiopathology ; Middle Aged ; },
abstract = {PURPOSE: In this study, differences in retinal feature visualization of high-resolution optical coherence tomography (OCT) devices were investigated with different axial resolutions in quantifications of retinal pigment epithelium and photoreceptors (PRs) in intermediate age-related macular degeneration.<br><br>METHODS: Patients were imaged with standard SPECTRALIS HRA + OCT and the investigational High-Res OCT device (both by Heidelberg Engineering, Heidelberg, Germany). Drusen, retinal pigment epithelium, and PR layers were segmented using validated artificial intelligence-based algorithms followed by manual corrections. Thickness and drusen maps were computed for all patients. Loss and thickness measurements were compared between devices, drusen versus nondrusen areas, and early treatment diabetic retinopathy study subfields using mixed-effects models.<br><br>RESULTS: Thirty-three eyes from 28 patients with intermediate age-related macular degeneration were included. Normalized PR integrity loss was significantly higher with 4.6% for standard OCT compared with 2.5% for High-Res OCT. The central and parafoveal PR integrity loss was larger than the perifoveal loss (P < 0.05). Photoreceptor thickness was increased on High-Res OCT and in nondrusen regions (P < 0.001). Retinal pigment epithelium appeared thicker on standard OCT and above drusen (P < 0.01).<br><br>CONCLUSION: Our study shows that High-Res OCT is able to identify the condition of investigated layers in intermediate age-related macular degeneration with higher precision. This improved in vivo imaging technology might promote our understanding of the pathophysiology and progression of age-related macular degeneration.},
}
@article {pmid39047135,
year = {2024},
author = {Matsumiya, W and Karaca, I and Pham, BH and Akhavanrezayat, A and Uludag, G and Yasar, C and Ghoraba, H and Mobasserian, A and Regenold, J and Halim, MS and Sepah, YJ and Do, DV and Chong, V and Nguyen, QD},
title = {Reply.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {8},
pages = {e53-e55},
pmid = {39047135},
issn = {1539-2864},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; EY026877/EY/NEI NIH HHS/United States ; },
abstract = {We wrote the letter in response to the insightful comments made by Dr. Vassallo J regarding our recently published study, “Association of Oral Montelukast with Reduced Odds of Developing Exudative Age-Related Macular Degeneration.” Our study underscored the potential treatment for AMD through managing mast cell activation.},
}
@article {pmid39046755,
year = {2024},
author = {Safai, A and Froines, C and Slater, R and Linderman, RE and Bogost, J and Pacheco, C and Voland, R and Pak, J and Tiwari, P and Channa, R and Domalpally, A},
title = {Quantifying Geographic Atrophy in Age-Related Macular Degeneration: A Comparative Analysis Across 12 Deep Learning Models.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {42},
pmid = {39046755},
issn = {1552-5783},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Deep Learning ; *Macular Degeneration/diagnosis/physiopathology ; Algorithms ; Fluorescein Angiography/methods ; Neural Networks, Computer ; Aged ; Female ; Male ; },
abstract = {PURPOSE: AI algorithms have shown impressive performance in segmenting geographic atrophy (GA) from fundus autofluorescence (FAF) images. However, selection of artificial intelligence (AI) architecture is an important variable in model development. Here, we explore 12 distinct AI architecture combinations to determine the most effective approach for GA segmentation.<br><br>METHODS: We investigated various AI architectures, each with distinct combinations of encoders and decoders. The architectures included three decoders-FPN (Feature Pyramid Network), UNet, and PSPNet (Pyramid Scene Parsing Network)-and serve as the foundation framework for segmentation task. Encoders including EfficientNet, ResNet (Residual Networks), VGG (Visual Geometry Group) and Mix Vision Transformer (mViT) have a role in extracting optimum latent features for accurate GA segmentation. Performance was measured through comparison of GA areas between human and AI predictions and Dice Coefficient (DC).<br><br>RESULTS: The training dataset included 601 FAF images from AREDS2 study and validation included 156 FAF images from the GlaxoSmithKline study. The mean absolute difference between grader measured and AI predicted areas ranged from -0.08 (95% CI = -1.35, 1.19) to 0.73 mm2 (95% CI = -5.75,4.29) and DC between 0.884-0.993. The best-performing models were UNet and FPN frameworks with mViT, and the least-performing models were PSPNet framework.<br><br>CONCLUSIONS: The choice of AI architecture impacts GA segmentation performance. Vision transformers with FPN and UNet architectures demonstrate stronger suitability for this task compared to Convolutional Neural Network- and PSPNet-based models. Selecting an AI architecture must be tailored to the specific goals of the project, and developers should consider which architecture is ideal for their project.},
}
@article {pmid39046116,
year = {2024},
author = {Su, YC and Shen, CY and Shao, SC and Lai, CC and Hsu, SM and Lee, CN and Liu, CJ and Hung, JH and Lai, EC},
title = {Risk of age-related macular degeneration in men receiving 5α-reductase inhibitors: a population-based cohort study.},
journal = {Age and ageing},
volume = {53},
number = {7},
pages = {},
doi = {10.1093/ageing/afae155},
pmid = {39046116},
issn = {1468-2834},
support = {NHRI-11A1-CG-CO-04-2225-1//National Health Research Institutes of Taiwan/ ; NSC 112-2628-B-006-003-//National Science and Technology Council of Taiwan/ ; MOST 110-2314-B-006-086-MY3//Ministry of Science and Technology/ ; NCKUH-11202007//National Cheng Kung University Hospital/ ; },
mesh = {Humans ; *5-alpha Reductase Inhibitors/adverse effects/therapeutic use ; Male ; Aged ; *Prostatic Hyperplasia/drug therapy/epidemiology ; Retrospective Studies ; Taiwan/epidemiology ; Incidence ; *Macular Degeneration/epidemiology/diagnosis/chemically induced ; *Dutasteride/therapeutic use/adverse effects ; *Tamsulosin/therapeutic use/adverse effects ; *Finasteride/adverse effects/therapeutic use ; Risk Factors ; Middle Aged ; Risk Assessment ; Databases, Factual ; },
abstract = {BACKGROUND: Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration.<br><br>OBJECTIVE: To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin.<br><br>DESIGN: Retrospective, population-based cohort study using new-user and active-comparator design.<br><br>SETTING: General population.<br><br>SUBJECTS: Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018.<br><br>METHODS: Data were extracted from Taiwan's National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs.<br><br>RESULTS: We included 13&#xa0;586 5ARIs users (mean age: 69&#xa0;years) and 54&#xa0;344 tamsulosin users (mean age: 68.37&#xa0;years). After a mean follow-up of 3.7&#xa0;years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98-1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02-1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87-1.12], in the subgroup analyses.<br><br>CONCLUSIONS: We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence.},
}
@article {pmid39044520,
year = {2024},
author = {Feldman, SJ and Blasco, D and Mones, M and Scott Roberts, J},
title = {Interest in and Experience with Genetic Testing for Late-Onset Medical Conditions: Results from the National Poll on Healthy Aging.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {11},
number = {4},
pages = {1079-1086},
pmid = {39044520},
issn = {2426-0266},
support = {P30 AG072931/AG/NIA NIH HHS/United States ; T32 AG000221/AG/NIA NIH HHS/United States ; T32 HG010030/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Genetic Testing/statistics &amp; numerical data ; Middle Aged ; Female ; Male ; Cross-Sectional Studies ; *Healthy Aging/genetics ; *Alzheimer Disease/genetics/diagnosis ; Parkinson Disease/genetics/diagnosis ; Surveys and Questionnaires ; Aged ; United States ; },
abstract = {BACKGROUND: The increasing availability of genetic testing for late-onset diseases such as Alzheimer's disease necessitates understanding public perceptions and experiences of such testing among at-risk populations.<br><br>OBJECTIVES: To assess (a) prior uptake of genetic testing (both in medical and direct-to-consumer settings), (b) future interest in genetic testing for late-onset conditions (e.g., Alzheimer's disease, Parkinson's disease), and (c) perceptions of testing pros and cons among middle-to-older aged adults.<br><br>DESIGN: Online, cross-sectional survey study.<br><br>SETTING: The National Poll on Healthy Aging at the University of Michigan is a recurring biannual survey of a nationally representative sample of adults aged 50-80. This study reports on a March 2018 fielding of the survey that included a genetic testing module administered to adults aged 50-64.<br><br>PARTICIPANTS: Study participants were 991 community-dwelling adults aged 50-64.<br><br>MEASUREMENTS: Survey measures assessed (a) prior use of genetic testing, (b) reasons for engaging in genetic testing, (c) interest in different types of genetic testing, including for Alzheimer's disease, Parkinson's disease, and macular degeneration, and (d) perceived benefits, risks, and limitations of testing.<br><br>RESULTS: Previous uptake of genetic testing was limited (medical use: 5.1%; direct-to-consumer: 10.8%), with direct-to-consumer test uptake higher among respondents with household incomes of $100,000 or more. Over half of adults endorsed interest in genetic testing for estimation of disease risk (58.9%), ancestry knowledge (58%), and informing medical care (53.8%). Interest in genetic testing for specific late-onset conditions was even higher, including Alzheimer's disease (70%), Parkinson's disease (65.3%), and macular degeneration (64.3%). Multivariable logistic regression models showed that older adults more likely to be interested in genetic testing for medical or disease risk purposes were those with higher levels of education (college degree or higher) and who endorsed the benefits of genetic testing, whereas respondents who endorsed testing risks and limitations were less likely to express interest.<br><br>CONCLUSION: While prior use of genetic testing among the middle-to-older age population was low, interest in testing for Alzheimer's disease and other late-onset conditions was high. This high interest may translate into increased uptake given expanded access to testing and recent treatment advances for Alzheimer's disease.},
}
@article {pmid39043575,
year = {2024},
author = {Samacá-Samacá, D and Hernández-Castillo, C and Prieto-Pinto, L and Rodríguez, F and Sardi, C and Ocampo, H and Kock, J and Hernández, F},
title = {Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {39043575},
issn = {2397-3269},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; *Intravitreal Injections ; *Visual Acuity/drug effects ; *Wet Macular Degeneration/drug therapy/physiopathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects/administration &amp; dosage ; },
abstract = {OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients.<br><br>METHODS AND ANALYSIS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for na&#xef;ve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively.<br><br>RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8&#x2009;weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk.<br><br>CONCLUSION: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients.<br><br>PROSPERO REGISTRATION NUMBER: CRD42023394226.},
}
@article {pmid39042402,
year = {2024},
author = {Jonas, JB and Bikbov, MM and Kazakbaeva, GM and Wang, YX and Xu, J and Jonas, RA and Panda-Jonas, S},
title = {Myopic Macular Atrophy in the Two-Continent Population-Based Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {38},
pmid = {39042402},
issn = {1552-5783},
mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; Prevalence ; Aged, 80 and over ; Adult ; *Myopia, Degenerative/epidemiology/complications ; *Macular Degeneration/epidemiology/diagnosis ; Tomography, Optical Coherence/methods ; Bruch Membrane/pathology ; China/epidemiology ; },
abstract = {PURPOSE: To examine the prevalence of Bruch's membrane defects (BMDs) and subretinal proliferations (SRPs) in highly myopic eyes with myopic macular atrophy (myopic macular degeneration [MMD] stage 4) and myopic patchy atrophies (MMD stage 3) in three ethnically different cohorts recruited in a population-based manner.<br><br>METHODS: The Ural Eye and Medical Study (UEMS) and Beijing Eye Study (BES) included individuals aged 40+&#xa0;years, and the Ural Very Old Study (UVOS) examined individuals aged 85+&#xa0;years. Main outcome measures were the prevalence of BMDs and SRPs.<br><br>RESULTS: Among 5794 UEMS participants, 19 eyes had MMD stage 4, with 17 (89%) eyes showing a foveal BMD; two eyes could not fully be explored. All 19 eyes showed localized SRPs. Among 21 eyes with MMD stage 3, BMD and SRP prevalence was 9 of 21 (44%) and 7 of 21 (33%), respectively. Among 930 UVOS participants, 17 eyes had MMD stage 4, with 16 (94%) eyes showing foveal BMDs and SRPs; one eye could not be assessed. Among 18 eyes with MMD stage 3, BMD and SRP prevalence was 3 of 18 (17%) and 2 of 18 (11%), respectively. Among 3468 BES participants, 8 eyes had MMD stage 4, with all eyes showing foveal BMDs and SRPs. Among 14 eyes with MMD stage 3, BMD and SRP prevalence was 10 of 14 (71%) and 7 of 21 (33%), respectively.<br><br>CONCLUSIONS: All eyes with assessable myopic macular atrophy showed foveal BMDs associated with SRPs, while patchy atrophies could be differentiated into those with BMDs and SRPs and those without BMDs and without SRPs. Independent of the MMD stage, the prevalences of BMDs and SRPs were highly significantly associated with each other.},
}
@article {pmid39042400,
year = {2024},
author = {Kar, D and Amjad, M and Corradetti, G and Swain, TA and Clark, ME and McGwin, G and Sloan, KR and Owsley, C and Sadda, SR and Curcio, CA},
title = {Choriocapillaris Impairment, Visual Function, and Distance to Fovea in Aging and Age-Related Macular Degeneration: ALSTAR2 Baseline.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {40},
pmid = {39042400},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/blood supply/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Male ; Aged ; Female ; *Visual Acuity/physiology ; *Fovea Centralis/diagnostic imaging/pathology/blood supply/physiopathology ; *Aging/physiology ; Middle Aged ; *Macular Degeneration/physiopathology ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Dark Adaptation/physiology ; },
abstract = {PURPOSE: In aging and early-intermediate age-related macular degeneration (AMD), rod-mediated dark adaptation (RMDA) slows more at 5° superior than at 12°. Using optical coherence tomography angiography (OCTA), we asked whether choriocapillaris flow deficits are related to distance from the fovea.<br><br>METHODS: Persons &#x2265;60&#xa0;years stratified for AMD via the Age-Related Eye Disease Study's nine-step system underwent RMDA testing. Two adjacent 4.4&#xb0; &#xd7; 4.4&#xb0; choriocapillaris OCTA slabs were centered on the fovea and 12&#xb0; superior. Flow signal deficits (FD%) in concentric arcs (outer radii in mm, 0.5, 1.5, 2.2, 4.0, and 5.0 superior) were correlated with rod intercept time (RIT) and best-corrected visual acuity (BCVA).<br><br>RESULTS: In 366 eyes (170 normal, 111 early AMD, 85 intermediate AMD), FD% was significantly worse with greater AMD severity in all regions (overall P < 0.05) and poorest under the fovea (P < 0.0001). In pairwise comparisons, FD% worsened with greater AMD severity (P < 0.05) at distances <2.2&#xa0;mm. At greater distances, eyes with intermediate, but not early AMD differed from normal eyes. Foveal FD% was more strongly associated with longer RIT at 5&#xb0; (r = 0.52) than RIT at 12&#xb0; (r = 0.39) and BCVA (r = 0.21; all P < 0.0001). Choroidal thickness was weakly associated with longer RIT at 5&#xb0; and 12&#xb0; (r = 0.10-0.20, P < 0.05) and not associated with AMD severity.<br><br>CONCLUSIONS: Reduced transport across the choriocapillaris-Bruch's membrane-retinal pigment epithelium complex, which contributes to drusen formation under the macula lutea (and fovea), may also reduce retinoid resupply to rods encircling the high-risk area. FD% has potential as a functionally validated imaging biomarker for AMD emergence.},
}
@article {pmid39042148,
year = {2024},
author = {Capuano, V and Sacconi, R and Miere, A and Borrelli, E and Amoroso, F and Costanzo, E and Parravano, M and Fragiotta, S and Bandello, F and Souied, EH and Querques, G},
title = {The "triple-layer sign": an optical coherence tomography signature for the detection of non-exudative macular neovascularization.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {12},
pages = {3847-3855},
pmid = {39042148},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Cross-Sectional Studies ; Aged ; *Retinal Pigment Epithelium/pathology ; *Fluorescein Angiography/methods ; Bruch Membrane/pathology ; Fundus Oculi ; Wet Macular Degeneration/diagnosis ; Retrospective Studies ; Macula Lutea/pathology/diagnostic imaging ; Reproducibility of Results ; Retinal Neovascularization/diagnosis/etiology ; Aged, 80 and over ; Visual Acuity ; },
abstract = {PURPOSE: To assess the sensitivity and specificity of the "triple layer sign" (TLS) (retinal pigment epithelium (RPE), neovascular tissue, and Bruch's membrane) on structural optical coherence tomography (OCT) images for the diagnosis of treatment-naïve non-exudative type-1 macular neovascularization (NE-MNV) in age-related macular degeneration (AMD).<br><br>DESIGN: Cross-sectional study.<br><br>METHODS: Two masked retinal experts evaluated the presence of the TLS in eyes with NE-MNV and controls with an RPE elevation without exudation due to other causes than NE-MNV in AMD [e.g., medium-large drusen, cuticular drusen, basal laminar deposits (BlamD)].<br><br>RESULTS: 130 eyes of 98 consecutive patients met the study criteria; 40 eyes of 40 patients satisfied the criteria for being included in the NE-MNV secondary to AMD group (27 females, 13 males, with a mean age of 73.8&#x2009;&#xb1;&#x2009;8.0&#xa0;years), and 90 eyes of 58 patients met the criteria to be included in the control group (31 eyes were included in the medium-to-large drusen sub-group, 32 eyes in the cuticular drusen sub-group, and 27 eyes in the BlamD group. The TLS was observed in 39/40 patients with NE-MNV and 8/90 controls. The sensitivity and specificity of the TLS for the diagnosis of NE-MNV were 97% and 91%, respectively.<br><br>CONCLUSIONS: The TLS on OCT demonstrated high sensitivity and specificity values in detecting treatment-naive type 1 NE-MNV.},
}
@article {pmid39042047,
year = {2024},
author = {Lombardo, M and Missiroli, F and Cerri, L and Sorge, RP and Cesareo, M and Ricci, F},
title = {Real-World Use of Off-Label MVASI in the Treatment of Patients With Neovascular AMD and DME.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {7},
pages = {17},
pmid = {39042047},
issn = {2164-2591},
mesh = {Humans ; Male ; *Bevacizumab/therapeutic use/administration &amp; dosage/adverse effects ; Female ; Retrospective Studies ; Aged ; *Off-Label Use ; *Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; *Visual Acuity/drug effects ; *Macular Edema/drug therapy ; *Intravitreal Injections ; Aged, 80 and over ; Diabetic Retinopathy/drug therapy ; Middle Aged ; Wet Macular Degeneration/drug therapy ; Drug Substitution ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Treatment Outcome ; },
abstract = {PURPOSE: The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME).<br><br>METHODS: All patients with n-AMD and DME treated in the maintenance phase according to the "treat and extend" strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events.<br><br>RESULTS: Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported.<br><br>CONCLUSIONS: In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator.<br><br>TRANSLATIONAL RELEVANCE: This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.},
}
@article {pmid39036487,
year = {2024},
author = {Boopathiraj, N and Wagner, IV and Dorairaj, SK and Miller, DD and Stewart, MW},
title = {Recent Updates on the Diagnosis and Management of Age-Related Macular Degeneration.},
journal = {Mayo Clinic proceedings. Innovations, quality &amp; outcomes},
volume = {8},
number = {4},
pages = {364-374},
pmid = {39036487},
issn = {2542-4548},
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the Western world, with a higher prevalence among Europeans and North Americans than that in Africans, Hispanics, and Asians. Advanced AMD is categorized as atrophic (dry) or exudative (wet/neovascular age-related macular degeneration [nAMD]). Dry AMD is characterized by progressive geographic atrophy of the retinal pigment epithelium and outer retinal layers, whereas nAMD is characterized by new vessels that invade the subretinal and/or subretinal pigment epithelium spaces. Existing treatments delay the onset of advanced AMD and reverses vision loss for a couple of years before atrophy usually decreases central visual acuity. We searched PubMed and Medline databases from January 1, 1980, to December 1, 2023, using the following search terms: macular degeneration, choroidal neovascularization, geographic atrophy, drusen, age-related maculopathy, AMD, ARMD, and anti-VEGF. Relevant articles in English (or English translations) were retrieved and reviewed. Bibliographies of the identified manuscripts were also reviewed to identify relevant studies. Age-related macular degeneration most commonly affects people older than 55 years. Visual prognosis varies, with advanced lesions (nAMD and geographic atrophy) leading to rapid, progressive loss of central vision and contrast sensitivity. Although AMD is not a life-threatening disease, reduced vision profoundly compromises quality of life and necessitates living assistance for many patients. Over the past 2 decades, advances in prevention (vitamin supplementation) and therapy (antivascular endothelial growth factor and complement inhibitor drugs) have reduced vision loss and blindness. Further research is needed to decrease the incidence of blindness in patients with advanced disease.},
}
@article {pmid39035512,
year = {2024},
author = {Sil Kar, S and Cetin, H and Srivastava, SK and Madabhushi, A and Ehlers, JP},
title = {Optical coherence tomography-derived texture-based radiomics features identify eyes with intraocular inflammation in the HAWK clinical trial.},
journal = {Heliyon},
volume = {10},
number = {13},
pages = {e32232},
pmid = {39035512},
issn = {2405-8440},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND AND OBJECTIVE: Intravitreal injection of anti-VEGF agents is the first-line treatment for patients with neovascular-age related macular degeneration (nAMD). One unique serious adverse event that may be associated with these agents is intraocular inflammation (IOI). The main purpose of this analysis was to evaluate the potential presence of texture-based radiomics features characterizing heterogeneity within the vitreous compartment of spectral domain optical coherence tomography (SD-OCT) images that may precede or develop in association with IOI and might serve as OCT biomarkers for IOI.<br><br>METHODS: This is a post-hoc analysis of a subset of cases (N&#xa0;=&#xa0;67) involving IOI, endophthalmitis, and/or retinal vascular occlusion in the phase 3 HAWK trial. These were investigator determined diagnoses that were also confirmed by the safety review committee. Intraocular inflammation was any signs of inflammation within the eye, endophthalmitis was inflammation associated with presumed infection, and retinal vascular occlusions consisted of intraocular inflammation with concurrent vascular occlusions/vasculitis. Out of 67 eyes, 34 belonged to the Safety group with an IOI event and 33 were propensity-matched Controls. A total of 481 texture-based radiomics features were extracted from the vitreous compartment of the SD-OCT scans at pre-IOI time point (i.e., much earlier than the actual event). Most discriminating five features, selected by the Wilcoxon Rank Sum feature selection were evaluated using Random Forest (RF) classifier on the training set (S t r , N&#xa0;=&#xa0;47) to differentiate between the two patient groups. Classifier performance was subsequently validated on the independent test set (S t , N&#xa0;=&#xa0;20). Additionally, the classifier performance in discriminating the Control and Safety group was also validated on S t at the IOI event timepoint.<br><br>RESULTS: The RF classifier yielded area under the Receiver Operating Characteristics curve (AUC) of 0.76 and 0.81 on S t using texture-based radiomics features at pre-IOI and event time-point, respectively.<br><br>CONCLUSIONS: In this analysis, the presence of a pre-IOI safety signal was detected in the form of textural heterogeneity within the vitreous compartment even prior to the actual event being identified by the investigator. This finding may help the clinicians to assess for underlying posterior inflammation.},
}
@article {pmid39034314,
year = {2024},
author = {Ghosh, S and Sharma, R and Bammidi, S and Koontz, V and Nemani, M and Yazdankhah, M and Kedziora, KM and Stolz, DB and Wallace, CT and Yu-Wei, C and Franks, J and Bose, D and Shang, P and Ambrosino, HM and Dutton, JR and Geng, Z and Montford, J and Ryu, J and Rajasundaram, D and Hose, S and Sahel, JA and Puertollano, R and Finkel, T and Zigler, JS and Sergeev, Y and Watkins, SC and Goetzman, ES and Ferrington, DA and Flores-Bellver, M and Kaarniranta, K and Sodhi, A and Bharti, K and Handa, JT and Sinha, D},
title = {The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {6150},
pmid = {39034314},
issn = {2041-1723},
support = {R01 EY031594/EY/NEI NIH HHS/United States ; 333302//Academy of Finland (Suomen Akatemia)/ ; R01 EY032516/EY/NEI NIH HHS/United States ; U01 EY034669/EY/NEI NIH HHS/United States ; P30 EY008098/EY/NEI NIH HHS/United States ; Postdoctoral Fellowship on Macular Degeneration//BrightFocus Foundation (BrightFocus)/ ; R01 EY028554/EY/NEI NIH HHS/United States ; },
mesh = {*Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism/genetics ; Animals ; *Proto-Oncogene Proteins c-akt/metabolism ; *Sirtuins/metabolism/genetics ; *Macular Degeneration/metabolism/pathology/genetics ; Humans ; Mice ; *Retinal Pigment Epithelium/metabolism/pathology ; *Lysosomes/metabolism ; *Signal Transduction ; *Autophagy ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Disease Models, Animal ; Induced Pluripotent Stem Cells/metabolism ; Male ; },
abstract = {Non-neovascular or dry age-related macular degeneration (AMD) is a multi-factorial disease with degeneration of the aging retinal-pigmented epithelium (RPE). Lysosomes play a crucial role in RPE health via phagocytosis and autophagy, which are regulated by transcription factor EB/E3 (TFEB/E3). Here, we find that increased AKT2 inhibits PGC-1α to downregulate SIRT5, which we identify as an AKT2 binding partner. Crosstalk between SIRT5 and AKT2 facilitates TFEB-dependent lysosomal function in the RPE. AKT2/SIRT5/TFEB pathway inhibition in the RPE induced lysosome/autophagy signaling abnormalities, disrupted mitochondrial function and induced release of debris contributing to drusen. Accordingly, AKT2 overexpression in the RPE caused a dry AMD-like phenotype in aging Akt2 KI mice, as evident from decline in retinal function. Importantly, we show that induced pluripotent stem cell-derived RPE encoding the major risk variant associated with AMD (complement factor H; CFH Y402H) express increased AKT2, impairing TFEB/TFE3-dependent lysosomal function. Collectively, these findings suggest that targeting the AKT2/SIRT5/TFEB pathway may be an effective therapy to delay the progression of dry AMD.},
}
@article {pmid39033924,
year = {2025},
author = {Khanani, AM and Sadda, SR and Sarraf, D and Tadayoni, R and Wong, DT and Kempf, AS and Saffar, I and Gedif, K and Chang, A},
title = {Effect of Brolucizumab and Aflibercept on the Maximum Thickness of Pigment Epithelial Detachments and Sub-Retinal Pigment Epithelium Fluid in HAWK and HARRIER.},
journal = {Ophthalmology. Retina},
volume = {9},
number = {1},
pages = {13-21},
doi = {10.1016/j.oret.2024.07.012},
pmid = {39033924},
issn = {2468-6530},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Double-Blind Method ; *Tomography, Optical Coherence/methods ; Prospective Studies ; *Intravitreal Injections ; *Retinal Pigment Epithelium/pathology/drug effects ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Female ; *Retinal Detachment/drug therapy/diagnosis ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Subretinal Fluid/drug effects ; Aged ; Treatment Outcome ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Fluorescein Angiography/methods ; Follow-Up Studies ; Dose-Response Relationship, Drug ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; },
abstract = {OBJECTIVE: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies.<br><br>DESIGN: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies.<br><br>PARTICIPANTS: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study.<br><br>INTERVENTION: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing.<br><br>MAIN OUTCOME MEASURES: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval).<br><br>RESULTS: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n&#xa0;= 336] vs. 11.9% [n&#xa0;= 335] in HAWK; 29.5% [n&#xa0;= 364] vs. 18.3% [n&#xa0;= 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week&#xa0;16.<br><br>CONCLUSIONS: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER).<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid39033785,
year = {2025},
author = {Nanji, K and Kennedy, K and Fung, M and Xie, J and Hatamnejad, A and Garg, SJ and Wykoff, CC and Chaudhary, V},
title = {Impact of COVID-19 on a real-world treat-and-extend regimen with aflibercept for neovascular age-related macular degeneration.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {1},
pages = {e92-e99},
doi = {10.1016/j.jcjo.2024.05.027},
pmid = {39033785},
issn = {1715-3360},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; *COVID-19/epidemiology ; Male ; Female ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Angiogenesis Inhibitors/administration &amp; dosage ; *SARS-CoV-2 ; Tomography, Optical Coherence ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Follow-Up Studies ; },
abstract = {OBJECTIVE: To assess the effect of the COVID-19 pandemic on injection intervals among patients treated for neovascular age-related macular degeneration.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Patients treated at a single practice using a treat-and-extend regimen with intravitreal aflibercept between December 2018 and April 2021.<br><br>METHODS: The primary outcome was the change in injection intervals. Secondary outcomes included differences in best-recorded visual acuity (BRVA) and central subfield thickness (CST). Associations were evaluated with linear mixed-effects modelling.<br><br>RESULTS: This study included 1839 injections from 185 eyes (141 patients). The median (interquartile range) injection intervals in the pre-COVID-19 and COVID-19 periods were 60 (42-70) and 70 (49-90) days, respectively. The pandemic was associated with a mean injection interval lengthening of 7.2 days (P < 0.001), a decrease in BRVA of 3.1 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and a reduction in CST of 14.7 &#x3bc;m (P&#x202f;=&#x202f;0.003). The presence of exudative intraretinal fluid was associated with a reduction in treatment intervals of 11.1 days (P < 0.001), a reduction in BRVA of 1.9 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and an increase in CST of 52.4 &#x3bc;m (P < 0.001). The presence of subretinal fluid was associated with a reduction in treatment intervals of 8.5 days (P < 0.001) and an increase in CST of 21.6 &#x3bc;m (P < 0.001).<br><br>CONCLUSIONS: This real-world study estimated that the severe acute respiratory syndrome coronavirus 2 pandemic resulted in an injection extension of 7.2 days with associated decreases in BRVA and CST that are unlikely clinically significant on a population basis. This builds on evidence suggesting that long-term vascular endothelial growth factor suppression can facilitate meaningful interval extensions while maintaining visual acuity.},
}
@article {pmid39033014,
year = {2024},
author = {Tang, Z and Wang, X and Ran, AR and Yang, D and Ling, A and Yam, JC and Zhang, X and Szeto, SKH and Chan, J and Wong, CYK and Hui, VWK and Chan, CKM and Wong, TY and Cheng, CY and Sabanayagam, C and Tham, YC and Liew, G and Anantharaman, G and Raman, R and Cai, Y and Che, H and Luo, L and Liu, Q and Wong, YL and Ngai, AKY and Yuen, VL and Kei, N and Lai, TYY and Chen, H and Tham, CC and Heng, PA and Cheung, CY},
title = {Deep learning-based image quality assessment for optical coherence tomography macular scans: a multicentre study.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {11},
pages = {1555-1563},
doi = {10.1136/bjo-2023-323871},
pmid = {39033014},
issn = {1468-2079},
mesh = {Adult ; Aged ; Child ; Female ; Humans ; Male ; Middle Aged ; *Deep Learning ; *Imaging, Three-Dimensional/methods/standards ; *Macula Lutea/diagnostic imaging/pathology ; Reproducibility of Results ; Retinal Diseases/diagnostic imaging/diagnosis ; Retrospective Studies ; *Tomography, Optical Coherence/methods/standards ; },
abstract = {AIMS: To develop and externally test deep learning (DL) models for assessing the image quality of three-dimensional (3D) macular scans from Cirrus and Spectralis optical coherence tomography devices.<br><br>METHODS: We retrospectively collected two data sets including 2277 Cirrus 3D scans and 1557 Spectralis 3D scans, respectively, for training (70%), fine-tuning (10%) and internal validation (20%) from electronic medical and research records at The Chinese University of Hong Kong Eye Centre and the Hong Kong Eye Hospital. Scans with various eye diseases (eg, diabetic macular oedema, age-related macular degeneration, polypoidal choroidal vasculopathy and pathological myopia), and scans of normal eyes from adults and children were included. Two graders labelled each 3D scan as gradable or ungradable, according to standardised criteria. We used a 3D version of the residual network (ResNet)-18 for Cirrus 3D scans and a multiple-instance learning pipline with ResNet-18 for Spectralis 3D scans. Two deep learning (DL) models were further tested via three unseen Cirrus data sets from Singapore and five unseen Spectralis data sets from India, Australia and Hong Kong, respectively.<br><br>RESULTS: In the internal validation, the models achieved the area under curves (AUCs) of 0.930 (0.885-0.976) and 0.906 (0.863-0.948) for assessing the Cirrus 3D scans and Spectralis 3D scans, respectively. In the external testing, the models showed robust performance with AUCs ranging from 0.832 (0.730-0.934) to 0.930 (0.906-0.953) and 0.891 (0.836-0.945) to 0.962 (0.918-1.000), respectively.<br><br>CONCLUSIONS: Our models could be used for filtering out ungradable 3D scans and further incorporated with a disease-detection DL model, allowing a fully automated eye disease detection workflow.},
}
@article {pmid39033013,
year = {2025},
author = {Zur, D and Guymer, R and Korobelnik, JF and Wu, L and Viola, F and Eter, N and Baillif, S and Chen, Y and Arnold, JJ},
title = {Impact of residual retinal fluid on treatment outcomes in neovascular age-related macular degeneration.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {3},
pages = {307-315},
pmid = {39033013},
issn = {1468-2079},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use ; *Subretinal Fluid/diagnostic imaging ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; Treatment Outcome ; Visual Acuity ; Fluorescein Angiography ; },
abstract = {Treatment decisions for neovascular age-related macular degeneration (nAMD) in the setting of individualised treatment regimens are adapted to disease activity. The main marker of disease activity and trigger for re-treatment with anti-vascular endothelial growth factor (anti-VEGF) agents is the presence of retinal fluid on optical coherence tomography (OCT). Recently, attention has focused on the impact of residual retinal fluid on nAMD management. Based on a literature review and the combined clinical experience of an international group of retinal specialists, this manuscript provides expert guidance on the treatment of nAMD according to fluid status and proposes an algorithm for determining when to administer anti-VEGF treatment according to residual fluid status. We explore the role of residual fluid in treatment decisions and outcomes in nAMD, taking into consideration fluid evaluation and, in particular, distinguishing between fluid in different anatomic compartments and at different stages during the treatment course. Current limitations to identifying and interpreting fluid on OCT, and the assumption that any residual retinal fluid reflects ongoing VEGF activity, are discussed.},
}
@article {pmid39031809,
year = {2024},
author = {Wu, Y and Li, X and Fu, X and Huang, X and Zhang, S and Zhao, N and Ma, X and Saiding, Q and Yang, M and Tao, W and Zhou, X and Huang, J},
title = {Innovative Nanotechnology in Drug Delivery Systems for Advanced Treatment of Posterior Segment Ocular Diseases.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {11},
number = {32},
pages = {e2403399},
pmid = {39031809},
issn = {2198-3844},
support = {82271048//National Nature Science Foundation of China/ ; 61905130//National Nature Science Foundation of China/ ; 23ZR1409500//Project of Shanghai Science and Technology/ ; 23XD1420500//Project of Shanghai Science and Technology/ ; 23S11900200//Project of Shanghai Science and Technology/ ; 22S11900200//Project of Shanghai Science and Technology/ ; 2021318//EYE &amp; ENT Hospital of Fudan University High-level Talents Program/ ; yg2023-06//Medical Engineering fund of Fudan University/ ; yg2023-206//Medical Engineering fund of Fudan University/ ; 2018M640145//Postdoctoral Science Foundation of China/ ; 2019T120106//Postdoctoral Science Foundation of China/ ; //Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning;/ ; },
mesh = {Humans ; *Drug Delivery Systems/methods ; *Eye Diseases/drug therapy ; Nanotechnology/methods ; Posterior Eye Segment/drug effects ; Animals ; Nanomedicine/methods ; Nanostructures ; Diabetic Retinopathy/drug therapy ; },
abstract = {Funduscopic diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti-vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next-generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally.},
}
@article {pmid39031277,
year = {2024},
author = {Lu, Y and Yu, X and Chen, Y and Wu, C and Jiang, Q and Ha, S and Zhu, D and Bi, Y and Liu, X and Zhang, H and Li, Z and Wang, W and Li, L and Chen, H and Zhang, Y and Dai, H and Fang, J},
title = {Safety and Efficacy of Multiple Escalating Doses of RC28-E for Neovascular Age-Related Macular Degeneration: A Phase 1b Trial.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {9},
pages = {2405-2415},
pmid = {39031277},
issn = {2193-8245},
abstract = {INTRODUCTION: To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled.<br><br>METHODS: Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0&#xa0;mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0&#xa0;mg. Patients were evaluated monthly for 48&#xa0;weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48.<br><br>RESULTS: Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0&#xa0;mg groups were 6.1&#x2009;&#xb1;&#x2009;8.3, 9.9&#x2009;&#xb1;&#x2009;10.7, and 7.6&#x2009;&#xb1;&#x2009;9.38 letters, respectively; mean reductions in CST in the three groups were 112.1&#x2009;&#xb1;&#x2009;160.5, 175.1&#x2009;&#xb1;&#x2009;212.4, and 128.7&#x2009;&#xb1;&#x2009;145.8&#xa0;&#x3bc;m, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48&#xa0;weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48&#xa0;weeks.<br><br>CONCLUSION: RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.},
}
@article {pmid39030410,
year = {2024},
author = {Liu, SH and Virgili, G},
title = {Cochrane Corner: Anti-vascular endothelial growth factor biosimilar for macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {16},
pages = {3045-3046},
pmid = {39030410},
issn = {1476-5454},
support = {UG1 EY020522/EY/NEI NIH HHS/United States ; UG1EY020522//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; },
}
@article {pmid39029747,
year = {2024},
author = {Vujosevic, S and Lupidi, M and Donati, S and Astarita, C and Gallinaro, V and Pilotto, E},
title = {Role of inflammation in diabetic macular edema and neovascular age-related macular degeneration.},
journal = {Survey of ophthalmology},
volume = {69},
number = {6},
pages = {870-881},
doi = {10.1016/j.survophthal.2024.07.006},
pmid = {39029747},
issn = {1879-3304},
mesh = {Humans ; *Macular Edema/etiology/drug therapy/physiopathology ; *Diabetic Retinopathy/physiopathology/drug therapy ; *Inflammation/physiopathology ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Glucocorticoids/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; },
abstract = {Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are multifactorial disorders that affect the macula and cause significant vision loss. Although inflammation and neoangiogenesis are hallmarks of DME and nAMD, respectively, they share some biochemical mediators. While inflammation is a trigger for the processes that lead to the development of DME, in nAMD inflammation seems to be the consequence of retinal pigment epithelium and Bruch membrane alterations. These pathophysiologic differences may be the key issue that justifies the difference in treatment strategies. Vascular endothelial growth factor inhibitors have changed the treatment of both diseases, however, many patients with DME fail to achieve the established therapeutic goals. From a clinical perspective, targeting inflammatory pathways with intravitreal corticosteroids has been proven to be effective in patients with DME. On the contrary, the clinical relevance of addressing inflammation in patients with nAMD has not been proven yet. We explore the role and implication of inflammation in the development of nAMD and DME and its therapeutical relevance.},
}
@article {pmid39028980,
year = {2024},
author = {Kumar, B and Mishra, M and Talreja, D and Cashman, S and Kumar-Singh, R},
title = {Cell-Penetrating Chaperone Nuc1 for Small- and Large-Molecule Delivery Into Retinal Cells and Tissues.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {31},
pmid = {39028980},
issn = {1552-5783},
mesh = {Animals ; Mice ; *Intravitreal Injections ; *Cell-Penetrating Peptides/administration &amp; dosage ; Mice, Inbred C57BL ; Drug Delivery Systems ; Retina/metabolism ; Molecular Chaperones/metabolism ; Disease Models, Animal ; Apoptosis ; Recombinant Proteins/administration &amp; dosage ; Humans ; },
abstract = {PURPOSE: There are currently no means available for the efficient delivery of recombinant proteins into retinal cells in vivo. Although cell-penetrating peptides have been somewhat effective in protein delivery to the retina, they generally require conjugation chemistry with the payload, negatively impacting function of the therapeutic protein. In this study, we developed a novel peptide (Nuc1) that acts as a chaperone for delivery of small and large molecules, including steroids, peptides, antibodies, recombinant proteins, and viruses (adeno-associated viruses [AAVs]) across biological membranes in vivo without the need for conjugation.<br><br>METHODS: Nuc1 peptide was designed based on sequences known to bind heparan sulfate proteoglycans and nucleolin found on the surface of retinal cells. Nuc1 was injected into the vitreous of mice with a variety of molecules and retinas examined for uptake and function of these molecules.<br><br>RESULTS: Nuc1 engages the process of macropynocytosis for cell entry. The delivery of functional recombinant X-linked inhibitor of apoptosis protein to photoreceptors via the intravitreal route of injection inhibited retinal apoptosis. Nuc1 was found to enhance the delivery of anti-VEGF antibodies delivered intravitreally or topically in models of age-related macular degeneration (AMD). Nuc1 enhanced delivery of decorin, facilitating significant inhibition of neovascularization and fibrosis in a model of AMD. Finally, Nuc1 was found to enhance penetration of retinal cells and tissues by AAV via both the subretinal and intravitreal routes of injection.<br><br>CONCLUSIONS: Nuc1 shows promise as a novel approach for the delivery of recombinant proteins into retinal cells in vivo.},
}
@article {pmid39028977,
year = {2024},
author = {Navneet, S and Ishii, M and Rohrer, B},
title = {Altered Elastin Turnover, Immune Response, and Age-Related Retinal Thinning in a Transgenic Mouse Model With RPE-Specific HTRA1 Overexpression.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {34},
pmid = {39028977},
issn = {1552-5783},
support = {I01 BX003050/BX/BLRD VA/United States ; I01 RX000444/RX/RRD VA/United States ; IK6 BX004858/BX/BLRD VA/United States ; R01 EY030072/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; Aging ; Autoantibodies/blood ; Complement C3/genetics/metabolism ; *Disease Models, Animal ; *Elastin/metabolism/genetics ; Gene Expression Regulation ; *High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism ; Immunoglobulin G/blood ; Immunohistochemistry ; *Macular Degeneration/genetics/metabolism ; *Mice, Transgenic ; *Retinal Pigment Epithelium/metabolism/pathology ; Serine Endopeptidases/genetics/metabolism ; *Tomography, Optical Coherence ; },
abstract = {PURPOSE: A single-nucleotide polymorphism in HTRA1 has been linked to age-related macular degeneration (AMD). Here we investigated the potential links between age-related retinal changes, elastin turnover, elastin autoantibody production, and complement C3 deposition in a mouse model with RPE-specific human HTRA1 overexpression.<br><br>METHODS: HTRA1 transgenic mice and age-matched CD1 wild-type mice were analyzed at 6 weeks and 4, 6, and 12 to 14&#xa0;months of age using in vivo retinal imaging by optical coherence tomography (OCT) and fundus photography, as well as molecular readouts, focusing on elastin and elastin-derived peptide quantification, antielastin autoantibody, and total Ig antibody measurements and immunohistochemistry to examine elastin, IgG, and C3 protein levels in retinal sections.<br><br>RESULTS: OCT imaging indicated thinning of inner nuclear layer as an early phenotype in HTRA1 mice, followed by age and age/genotype-related thinning of the photoreceptor layer, RPE, and total retina. HTRA1 mice exhibited reduced elastin protein levels in the RPE/choroid and increased elastin breakdown products in the retina and serum. A corresponding age-dependent increase of serum antielastin IgG and IgM autoantibodies and total Ig antibody levels was observed. In the RPE/choroid, these changes were associated with an age-related increase of IgG and C3 deposition.<br><br>CONCLUSIONS: Our results confirm that RPE-specific overexpression of human HTRA1 induces certain AMD-like phenotypes in mice. This includes altered elastin turnover, immune response, and complement deposition in the RPE/choroid in addition to age-related outer retinal and photoreceptor layer thinning. The identification of elastin-derived peptides and corresponding antielastin autoantibodies, together with increased C3 deposition in the RPE/choroid, provides a rationale for an overactive complement system in AMD irrespective of the underlying genetic risk.},
}
@article {pmid39028975,
year = {2024},
author = {Wu, L and Foo, LL and Hu, Z and Pan, W and Jiang, Y and Saw, SM and Hoang, QV and Lan, W},
title = {Bruch's Membrane Opening Changes in Eyes With Myopic Macular Degeneration: AIER-SERI Adult High Myopia Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {36},
pmid = {39028975},
issn = {1552-5783},
mesh = {Humans ; *Bruch Membrane/pathology/diagnostic imaging ; Male ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; Female ; *Visual Acuity/physiology ; *Myopia, Degenerative/physiopathology/complications/diagnosis ; Middle Aged ; Adult ; *Macular Degeneration/physiopathology/diagnosis ; Choroid/pathology/diagnostic imaging ; Aged ; },
abstract = {PURPOSE: The purpose of this study was to assess the choroidal thickness and the Bruch's membrane opening size and their relationship to visual acuity in eyes with myopic macular degeneration (MMD).<br><br>METHODS: This was a population-based, cross-sectional study. Patients over the age of 30&#xa0;years with high myopia (spherical equivalent &#x2264;-5 diopters [D]) were recruited. The eyes were grouped according to the International Meta-Analysis for Pathologic Myopia (META-PM) classification based on fundus photographs and diffuse atrophy was subdivided into peripapillary diffuse choroidal atrophy (PDCA) or macular diffuse choroidal atrophy (MDCA). Swept-source optical coherence tomography imaging was performed and then the subfoveal choroidal thickness (SFCT) and Bruch's membrane opening diameter (BMOD) were measured.<br><br>RESULTS: Of the 470 study participants recruited, 373 patients (691 eyes), with a mean age of 42.8 &#xb1; 7.2&#xa0;years, were eligible for the study and included in the analysis. There was no significant difference in SFCT between MDCA and patchy atrophy (M3) groups (P = 1.000), and the BMOD enlarged significantly from no myopic macular lesions to M3 (the P values of multiple comparison tests were all <0.005). Simple linear regression analysis showed that BMOD correlated positively with age (P < 0.001) and axial length (P < 0.001). Multiple linear regression analysis showed that best corrected visual acuity (BCVA) was significantly correlated with age (P = 0.041), axial length (P = 0.001), and BMOD (P = 0.017), but not with SFCT (P = 0.231).<br><br>CONCLUSIONS: The significant variation of BMOD among MMD groups and the correlation between BMOD and BCVA in MMD eyes suggest that BMOD may be an imaging biomarker for monitoring MMD.},
}
@article {pmid39027974,
year = {2024},
author = {Cheng, JY and Santina, A and Margines, JB and Voichanski, S and Ramtohul, P and Bousquet, E and Bijon, J and Freund, KB and Yannuzzi, L and Sarraf, D},
title = {ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY AND PLACOID VARIANT DISEASES MASQUERADING AS AGE-RELATED MACULAR DEGENERATION IN THE ELDERLY: A Case Series.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {10},
pages = {1666-1678},
doi = {10.1097/IAE.0000000000004191},
pmid = {39027974},
issn = {1539-2864},
support = {//Research to Prevent Blindness/ ; },
mesh = {Humans ; Male ; Aged ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Middle Aged ; Diagnosis, Differential ; *Retinal Pigment Epithelium/pathology ; *Visual Acuity ; *Multimodal Imaging ; Macular Degeneration/diagnosis ; Acute Disease ; Indocyanine Green/administration &amp; dosage ; Aged, 80 and over ; Retrospective Studies ; Fundus Oculi ; Coloring Agents/administration &amp; dosage ; Retinal Diseases/diagnosis ; },
abstract = {PURPOSE: To report eight cases of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or persistent placoid maculopathy (PPM) initially masquerading as age-related macular degeneration in elderly individuals.<br><br>METHODS: APMPPE or PPM eyes in patients above age 55 years with macular retinal pigment epithelium disruption including drusenoid lesions on macular examination and/or with multimodal imaging were included. At least one method of multimodal imaging including fluorescein angiography (FA), indocyanine green angiography, optical coherence tomography (OCT), and OCT angiography (OCTA) was performed in all eyes for diagnosis and to monitor for macular neovascularization.<br><br>RESULTS: Eight elderly male patients presented with vision loss and were all initially diagnosed with non-neovascular or neovascular age-related macular degeneration. With the aid of multimodal retinal imaging, a final diagnosis of either APMPPE or PPM was rendered. With FA and indocyanine green angiography, choroidal hypoperfusion was detected in all but one eye. With OCT, the angular sign of Henle fiber layer hyperreflectivity was identified in >50% of eyes. With OCTA, inner choroidal flow deficits were detected in all eyes. Macular neovascularization requiring anti-vascular endothelial growth factor injection therapy complicated three of eight cases.<br><br>CONCLUSION: Both APMPPE and PPM may develop in elderly individuals and may masquerade as age-related macular degeneration on presentation. Multimodal imaging including FA, indocyanine green angiography, and OCTA are important diagnostic modalities to assess for inner choroidal hypoperfusion to arrive at an accurate diagnosis and to detect macular neovascularization, which frequently complicates APMPPE and PPM. In these patients, serial anti-vascular endothelial growth factor intravitreal injections are essential in treating macular neovascularization and in preventing significant vision loss.},
}
@article {pmid39027747,
year = {2024},
author = {Subramanian, B and Kumar, M and Sen, P and Raman, R},
title = {Optical Coherence Tomography Characteristics for Differentiating Scars in Type 1 (Polypoidal Choroidal Vasculopathy (PCV)) and Type 2 (Classical) Macular Neovascularization (MNV) in Age-Related Macular Degeneration (AMD).},
journal = {Cureus},
volume = {16},
number = {6},
pages = {e62593},
pmid = {39027747},
issn = {2168-8184},
abstract = {PURPOSE: This study aimed to assess the optical coherence tomography (OCT) characteristics for differentiating scars in the scarred stages of macular neovascularization (MNV) in age-related macular degeneration (AMD).<br><br>METHODS: Medical records of 20 patients, 10 in each group with type 1 and type 2 MNV, were selected for the study. Participants chosen were above 50 years of age and underwent comprehensive eye examination alongside indocyanine green angiography (ICGA), fundus fluorescence angiography (FFA), and Spectralis optical coherence tomography (SOCT) (Heidelberg Engineering, Germany), respectively. The qualitative and quantitative OCT measurements, such as the frequency of outer retinal tubulations, presence of cystoid spaces, scar area, choroid thickness, retinal thickness, presence of disorganization in retinal layers (DRIL), foveal contour, and involvement of retinal layers in the scar, were meticulously evaluated and compared between the two groups.<br><br>RESULTS: Significant disparities between type 1 MNV and type 2 MNV in choroidal thickness were identified in the nasal and superior quadrants within 1 mm, in the superior quadrant within 3 mm, and in all quadrants except the inferior quadrant within 6 mm. Overall, type 2 MNV showed thinner choroid than type 1 MNV.<br><br>CONCLUSION: Although there are several overlapping features noticed between the groups, the OCT was able to pick up characteristic features that aid in differentiating type 1 (polypoidal choroidal vasculopathy (PCV)) and type 2 (classic) MNV in AMD. This precise differentiation has the potential to assist ophthalmologists in making well-informed decisions, thereby enhancing patient care.},
}
@article {pmid39027060,
year = {2024},
author = {Sharma, S and Rose, L and Schulz, A and Sharma, DP and Zeldovich, A and Azzi, C and Nischal, K},
title = {Myopia intervention and ultraviolet radiation related eye diseases: A narrative literature review.},
journal = {Taiwan journal of ophthalmology},
volume = {14},
number = {2},
pages = {151-158},
pmid = {39027060},
issn = {2211-5072},
abstract = {There has been an increased understanding of the protective effect of two or more hours in high lux light on the development and progression of myopia. The aim of myopia management is to reduce the incidence of high myopia and sight-threatening myopic complications. Equally important are the sight-threatening complications of ultraviolet radiation (UVR) on the eye and adnexal structures. This review will analyze the literature for both these epidemics to help guide public health policy. Whilst increasing childhood high lux light exposure is important, consideration of a holistic eye health policy should ensure that UV eye diseases are also prevented. The advent of ultraviolet (UV) fluorescence photography has increased our understanding that significant UV eye damage occurs in childhood, with 81% of children aged 12-15 years having signs of UV eye damage. Hence, the need to reduce myopia and protect from UV-related eye diseases needs simultaneous consideration. Advocating for eye protection is important, particularly as the natural squint reflex is disabled with dark sunglasses lenses. The pathways UV reaches the eye need to be considered and addressed to ensure that sunglasses offer optimum UV eye protection. The design of protective sunglasses that simultaneously allow high lux light exposure and protect from UVR is critical in combating both these epidemics.},
}
@article {pmid39026906,
year = {2024},
author = {Hu, ZL and Wang, YX and Lin, ZY and Ren, WS and Liu, B and Zhao, H and Qin, Q},
title = {Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis.},
journal = {International journal of ophthalmology},
volume = {17},
number = {7},
pages = {1344-1362},
pmid = {39026906},
issn = {2222-3959},
abstract = {Age-related macular degeneration (AMD) is a complicated disease that causes irreversible visual impairment. Increasing evidences pointed retinal pigment epithelia (RPE) cells as the decisive cell involved in the progress of AMD, and the function of anti-oxidant capacity of PRE plays a fundamental physiological role. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a significant transcription factor in the cellular anti-oxidant system as it regulates the expression of multiple anti-oxidative genes. Its functions of protecting RPE cells against oxidative stress (OS) and ensuing physiological changes, including inflammation, mitochondrial damage and autophagy dysregulation, have already been elucidated. Understanding the roles of upstream regulators of Nrf2 could provide further insight to the OS-mediated AMD pathogenesis. For the first time, this review summarized the reported upstream regulators of Nrf2 in AMD pathogenesis, including proteins and miRNAs, and their underlying molecular mechanisms, which may help to find potential targets via regulating the Nrf2 pathway in the future research and further discuss the existing Nrf2 regulators proved to be beneficial in preventing AMD.},
}
@article {pmid39025435,
year = {2025},
author = {Keenan, TDL and Agrón, E and Keane, PA and Domalpally, A and Chew, EY and , and , },
title = {Oral Antioxidant and Lutein/Zeaxanthin Supplements Slow Geographic Atrophy Progression to the Fovea in Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {132},
number = {1},
pages = {14-29},
pmid = {39025435},
issn = {1549-4713},
support = {Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Administration, Oral ; *Antioxidants/administration &amp; dosage ; Ascorbic Acid/administration &amp; dosage ; beta Carotene/administration &amp; dosage ; *Dietary Supplements ; Disease Progression ; Docosahexaenoic Acids/administration &amp; dosage ; Eicosapentaenoic Acid/administration &amp; dosage ; *Fovea Centralis/pathology ; *Geographic Atrophy/drug therapy/diagnosis ; *Lutein/administration &amp; dosage ; *Macular Degeneration/drug therapy/diagnosis ; Visual Acuity/physiology ; Vitamin E/administration &amp; dosage ; *Zeaxanthins/administration &amp; dosage ; Zinc/administration &amp; dosage ; },
abstract = {PURPOSE: To determine whether oral micronutrient supplementation slows geographic atrophy (GA) progression in age-related macular degeneration (AMD).<br><br>DESIGN: Post hoc analysis of Age-Related Eye Disease Study (AREDS) and AREDS2, multicenter randomized placebo-controlled trials of oral micronutrient supplementation, each with 2&#xa0;&#xd7; 2 factorial design.<br><br>PARTICIPANTS: A total of 392 eyes (318 participants) with GA in AREDS and 1210 eyes (891 participants) with GA in AREDS2.<br><br>METHODS: The AREDS participants were randomly assigned to oral antioxidants (500 mg vitamin C, 400 IU vitamin E, 15 mg &#x3b2;-carotene), 80 mg zinc, combination, or placebo. The AREDS2 participants were randomly assigned to 10 mg lutein/2 mg zeaxanthin, 350 mg docosahexaenoic acid/650 mg eicosapentaenoic acid, combination, or placebo. Consenting AREDS2 participants were also randomly assigned to alternative AREDS formulations: original; no beta-carotene; 25 mg zinc instead of 80 mg; both.<br><br>MAIN OUTCOME MEASURES: (1) Change in GA proximity to central macula over time and (2) change in square root GA area over time, each measured from color fundus photographs at annual visits and analyzed by mixed-model regression according to randomized assignments.<br><br>RESULTS: In AREDS eyes with noncentral GA (n&#xa0;= 208), proximity-based progression toward the central macula was significantly slower with randomization to antioxidants versus none, at 50.7 &#x3bc;m/year (95% confidence interval [CI], 38.0-63.4 &#x3bc;m/year) versus 72.9 &#x3bc;m/year (95% CI, 61.3-84.5 &#x3bc;m/year; P&#xa0;= 0.012), respectively. In AREDS2 eyes with noncentral GA, in participants assigned to AREDS antioxidants without &#x3b2;-carotene (n&#xa0;= 325 eyes), proximity-based progression was significantly slower with randomization to lutein/zeaxanthin versus none, at 80.1 &#x3bc;m/year (95% CI, 60.9-99.3 &#x3bc;m/year) versus 114.4 &#x3bc;m/year (95% CI, 96.2-132.7 &#x3bc;m/year; P&#xa0;= 0.011), respectively. In AREDS eyes with any GA (n&#xa0;= 392), area-based progression was not significantly different with randomization to antioxidants versus none (P&#xa0;= 0.63). In AREDS2 eyes with any GA, in participants assigned to AREDS antioxidants without &#x3b2;-carotene (n&#xa0;= 505 eyes), area-based progression was not significantly different with randomization to lutein/zeaxanthin versus none (P&#xa0;= 0.64).<br><br>CONCLUSIONS: Oral micronutrient supplementation slowed GA progression toward the central macula, likely by augmenting the natural phenomenon of foveal sparing.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid39025232,
year = {2024},
author = {Son-Camey, B and Rosado-Cerro, I and Escámez-Fernández, P and Liaño Sanz Diez de Ulzurrun, G and Montejano-Milner, R and Arruabarrena, C},
title = {Long-term results of the treatment of patients with exudative age-related macular degeneration during the COVID-19 pandemic.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {99},
number = {11},
pages = {477-484},
doi = {10.1016/j.oftale.2024.07.004},
pmid = {39025232},
issn = {2173-5794},
mesh = {Humans ; *COVID-19 ; Retrospective Studies ; Female ; Male ; Aged ; Aged, 80 and over ; *Angiogenesis Inhibitors/therapeutic use ; Wet Macular Degeneration/drug therapy ; Visual Acuity ; Intravitreal Injections ; Pandemics ; Follow-Up Studies ; Time Factors ; Treatment Outcome ; Quarantine ; Middle Aged ; SARS-CoV-2 ; },
abstract = {PURPOSE: To quantify the long-term impact (24 months) on the visual results and activity of neovascular lesions of COVID-19 confinement in patients with nAMD in our population.<br><br>METHODS: A retrospective observational study of patients with nAMD who attended consultation or were treated during the 3 months before confinement was carried out.<br><br>RESULTS: 144 patients (168 eyes) with nAMD were included, 51 of them (35.42%) came during confinement, and at 24 months the final cohort was 118 patients (133 eyes). The previous VA of 57.99&#x202f;&#xb1;&#x202f;23.68 letters decreased, clinically relevant and statistically significant, by an average of 6.87 (&#xb1;16.84) and 7.89 (&#xb1;19.58) at 12- and 24-months follow-up. This change differs significantly from the two-year vision change observed in the national database of pretreated patients. The median number of injections and consultations is lower in our group at 12 months, compared to the pre-pandemic national database, and tends to equalize at 24 months. We did not find differences in vision when we compared patients who attended consultations during confinement or in treatment intervals greater than 8 weeks (Tq8w).<br><br>CONCLUSIONS: The VA of patients with nAMD decreased significantly after confinement, probably due to the lower number of antiangiogenic injections and consultations during the first year, and did not recover during the second year despite the increase in the number of injections and visits close to those reported before confinement.},
}
@article {pmid39024499,
year = {2024},
author = {Sudhakaran, G},
title = {Letter to Editor: Comment on Ioanna Tsioti et al. "Systemic Lipopolysaccharide Exposure Exacerbates Choroidal Neovascularization in Mice".},
journal = {Ocular immunology and inflammation},
volume = {32},
number = {10},
pages = {2616-2617},
doi = {10.1080/09273948.2024.2377736},
pmid = {39024499},
issn = {1744-5078},
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/metabolism ; Mice ; *Lipopolysaccharides ; *Disease Models, Animal ; *Fluorescein Angiography ; Vascular Endothelial Growth Factor A/genetics/metabolism ; Macrophages ; Flow Cytometry ; },
abstract = {This study by Ioanna Tsioti and colleagues delves into the exacerbation of choroidal neovascularization (CNV) through systemic exposure to lipopolysaccharide (LPS) in a mouse model. The research highlights the molecular and cellular mechanisms by which systemic inflammation can influence ocular conditions, particularly in the context of age-related macular degeneration (AMD). Utilizing a combination of in vivo fluorescein angiography, in situ hybridization, and flow cytometry, the study provides critical insights into the dynamic interaction between systemic inflammatory stimuli and CNV progression. Key findings include increased infiltration of monocyte-derived macrophages and enhanced Vegfα mRNA expression in Glul-expressing cells following systemic LPS exposure. These results suggest potential therapeutic targets for mitigating CNV associated with systemic inflammatory responses.},
}
@article {pmid39023641,
year = {2024},
author = {Kalogeropoulos, D and De Salvo, G and Antonakis, S},
title = {An Epiretinal Roller Coaster Effect.},
journal = {JAMA ophthalmology},
volume = {142},
number = {7},
pages = {e240217},
doi = {10.1001/jamaophthalmol.2024.0217},
pmid = {39023641},
issn = {2168-6173},
mesh = {Humans ; *Tomography, Optical Coherence ; Epiretinal Membrane/diagnosis ; Visual Acuity/physiology ; Male ; Female ; Fluorescein Angiography ; },
}
@article {pmid39023220,
year = {2024},
author = {Hogg, RE and Wickens, R and O'Connor, S and Gidman, E and Ward, E and Treanor, C and Peto, T and Burton, B and Knox, P and Lotery, AJ and Sivaprasad, S and Donnelly, M and Rogers, CA and Reeves, BC},
title = {Home-monitoring for neovascular age-related macular degeneration in older adults within the UK: the MONARCH diagnostic accuracy study.},
journal = {Health technology assessment (Winchester, England)},
volume = {28},
number = {32},
pages = {1-136},
pmid = {39023220},
issn = {2046-4924},
mesh = {Humans ; United Kingdom ; Aged ; Male ; Female ; Aged, 80 and over ; *Macular Degeneration/diagnosis ; Visual Acuity ; Technology Assessment, Biomedical ; },
abstract = {BACKGROUND: Most neovascular age-related macular degeneration treatments involve long-term follow-up of disease activity. Home monitoring would reduce the burden on patients and those they depend on for transport, and release clinic appointments for other patients. The study aimed to evaluate three home-monitoring tests for patients to use to detect active neovascular age-related macular degeneration compared with diagnosing active neovascular age-related macular degeneration by hospital follow-up.<br><br>OBJECTIVES: There were five objectives: Estimate the accuracy of three home-monitoring tests to detect active neovascular age-related macular degeneration. Determine the acceptability of home monitoring to patients and carers and adherence to home monitoring. Explore whether inequalities exist in recruitment, participants' ability to self-test and their adherence to weekly testing during follow-up. Provide pilot data about the accuracy of home monitoring to detect conversion to neovascular age-related macular degeneration in fellow eyes of patients with unilateral neovascular age-related macular degeneration. Describe challenges experienced when implementing home-monitoring tests.<br><br>DESIGN: Diagnostic test accuracy cohort study, stratified by time since starting treatment.<br><br>SETTING: Six United Kingdom Hospital Eye Service macular clinics (Belfast, Liverpool, Moorfields, James Paget, Southampton, Gloucester).<br><br>PARTICIPANTS: Patients with at least one study eye being monitored by hospital follow-up.<br><br>REFERENCE STANDARD: Detection of active neovascular age-related macular degeneration by an ophthalmologist at hospital follow-up.<br><br>INDEX TESTS: KeepSight Journal: paper-based near-vision tests presented as word puzzles. MyVisionTrack&#xae;: electronic test, viewed on a tablet device. MultiBit: electronic test, viewed on a tablet device. Participants provided test scores weekly. Raw scores between hospital follow-ups were summarised as averages.<br><br>RESULTS: Two hundred and ninety-seven patients (mean age 74.9 years) took part. At least one hospital follow-up was available for 317 study eyes, including 9 second eyes that became eligible during follow-up, in 261 participants (1549 complete visits). Median testing frequency was three times/month. Estimated areas under receiver operating curves were < 0.6 for all index tests, and only KeepSight Journal summary score was significantly associated with the lesion activity (odds ratio&#x2005;=&#x2005;3.48, 95% confidence interval 1.09 to 11.13, p&#x2005;=&#x2005;0.036). Older age and worse deprivation for home address were associated with lower participation (&#x3c7;[2]&#x2005;=&#x2005;50.5 and 24.3, respectively, p&#x2005;<&#x2005;0.001) but not ability or adherence to self-testing. Areas under receiver operating curves appeared higher for conversion of fellow eyes to neovascular age-related macular degeneration (0.85 for KeepSight Journal) but were estimated with less precision. Almost half of participants called a study helpline, most often due to inability to test electronically.<br><br>LIMITATIONS: Pre-specified sample size not met; participants' difficulties using the devices; electronic tests not always available.<br><br>CONCLUSIONS: No index test provided adequate test accuracy to identify lesion diagnosed as active in follow-up clinics. If used to detect conversion, patients would still need to be monitored at hospital. Associations of older age and worse deprivation with study participation highlight the potential for inequities with such interventions. Provision of reliable electronic testing was challenging.<br><br>FUTURE WORK: Future studies evaluating similar technologies should consider: Independent monitoring with clear stopping rules based on test performance. Deployment of apps on patients' own devices since providing devices did not reduce inequalities in participation and complicated home testing. Alternative methods to summarise multiple scores over the period preceding a follow-up.<br><br>TRIAL REGISTRATION: This trial is registered as ISRCTN79058224.<br><br>FUNDING: This award was funded by the National Institute of Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/97/02) and is published in full in Health Technology Assessment; Vol. 28, No. 32. See the NIHR Funding and Awards website for further award information.},
}
@article {pmid39023151,
year = {2024},
author = {Pepin, M and Gohier, P and Annweiler, C},
title = {[Ophthalmological traits in older adult and risk of Alzheimer's disease: results from a French geriatric cohort].},
journal = {Geriatrie et psychologie neuropsychiatrie du vieillissement},
volume = {22},
number = {2},
pages = {159-165},
doi = {10.1684/pnv.2024.1168},
pmid = {39023151},
issn = {2115-7863},
mesh = {Humans ; *Alzheimer Disease ; Female ; Male ; Aged ; France ; Cohort Studies ; *Disease Progression ; Aged, 80 and over ; Risk Factors ; Tomography, Optical Coherence ; Retinal Ganglion Cells/pathology ; },
abstract = {Ophthalmological changes have been reported in Alzheimer's patients. Our objectives were to determine whether: i) GCC (ganglion cell complex) and RNFL (retinal nerve fibre layer) thickness were associated with different stages of AD (i.e., no AD, prodromal AD, dementia-stage AD), and ii) GCC and RNFL thickness predicted disease progression in older non-demented patients with subjective memory complaints followed for four years. Ninety-one French older community-dwellers with memory complaint and without open-angle glaucoma or age-related macular degeneration (mean, 71.60 ± 4,73 years; 44% women) from the GAIT study underwent examination with HD-OCT, measuring the thickness of the macula, the macular GCC and the RNFL. They also had a complete cognitive diagnosis (i.e., cognitively healthy, prodromal AD, or dementia AD), and a cognitive follow-up 4 years later looking for a possible conversion. Age, sex, body mass index (BMI), number of comorbidities, and Instrumental activities of daily living (IADL) score were considered as potential confounders. At baseline, 37 (40.7%) patients were diagnosed as cognitively healthy, 47 (51.6%) as MCI, and 7 (7.7%) as AD. Mean GCC thickness was higher in cognitively healthy patients than in MCI patients (79.23 vs. 76.27 μm, p = 0.023), particularly in the inferior and nasal fields (p = 0.023 and p = 0.005, respectively). This difference was also found between cognitively healthy patients and others (MCI and AD) in the superior, inferior and nasal fields (p = 0.030, p = 0.014 and p = 0.002, respectively). There was no difference in RNFL thickness between the different cognitive statuses. After 4 years of follow-up, 12 patients (70.6%) of the 17 followed had not changed their cognitive status, while 5 (29.4%) had converted to a more advanced stage of AD. There were no significant differences between the two groups in either GCC thickness (p = 0.429) or RNFL thickness (p = 0.286). We found decreased CGG thicknesses in Alzheimer's patients at prodromal and dementia stages, compared with cognitively healthy participants. There was no association between RNFL thickness and cognitive status, nor between CCG or RNFL thicknesses and the risk of progressing to AD stages after 4 years of follow-up.},
}
@article {pmid39022525,
year = {2024},
author = {Tricorache, DF and Dascalu, AM and Alexandrescu, C and Bobirca, A and Grigorescu, C and Tudor, C and Cristea, BM},
title = {Correlations Between the Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio, and Serum Lipid Fractions With Neovascular Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {16},
number = {6},
pages = {e62503},
pmid = {39022525},
issn = {2168-8184},
abstract = {Introduction Age-related macular degeneration, a chronic and progressive disease, is one of the leading causes of vision loss globally among the elderly population. Multiple hypotheses have been proposed regarding its pathogenesis, including the presence of lipid metabolism alteration. Dysfunctional lipid handling within retinal pigment epithelial cells has been implicated in the accumulation of lipofuscin and subsequent induction of oxidative stress and inflammation, all contributing to retinal degeneration. The present study aims to comparatively analyze the serum lipid fraction distributions in patients with neovascular age-related macular degeneration (AMD) and controls. Materials and methods A retrospective study was carried out between January 2021 and December 2023 on 91 naïve patients with neovascular AMD and 90 controls admitted for routine cataract surgery. All subjects underwent a comprehensive ophthalmological exam, including ophthalmoscopy and optical coherence tomography (OCT) with central macular thickness (CMT) measurement. A complete blood count with differential and lipid fractions values was analyzed. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were comparatively analyzed between the control group and the test group. Results The groups were comparable in terms of age (73.84 ±7.52 years for the neovascular AMD group vs 72.1±10.92 years in controls; p=0.8) and gender distribution (p=0.243). The mean NLR and PLR values were slightly higher in the AMD group but not statistically significant (p=0.51, p>0.99, respectively). Comparative analysis of lipid profile fractions showed significantly higher HDL-C values in the exudative AMD group compared to normal subjects (61.27±19.4 mg/dL vs 50.99±7.86 mg/dL, p=0.006). Also, the proportion of subjects with HDL-C>60 mg/dL was higher in the exudative AMD group (p=0.014). There were no significant differences in total cholesterol (189.77±53.39 mg/dL vs 190.43±37.84 mg/dL, p=0.681), LDL-C, and TG. Logistic regression analysis showed that serum HDL-C and HDL-C values >60 mg/dL are significantly associated factors with neovascular AMD. However, there is no statistical correlation between the values of these biochemical parameters and visual acuity or CMT in the neovascular AMD patient group. Conclusions There were no correlations between NLR and PLR with neovascular AMD in the study group. Higher HDL-C values exceeding 60 mg/dL were associated with neovascular age-related macular degeneration and could represent a possible therapeutic target in neovascular AMD.},
}
@article {pmid39018483,
year = {2024},
author = {Chang, W and Lv, X and Zhu, J and Shen, JJ and Yao, J and Liu, Z and Chen, Q},
title = {Multifunctional Nanotherapeutics with Long-Acting Release against Macular Degeneration by Minimally Invasive Administration.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.4c04494},
pmid = {39018483},
issn = {1936-086X},
abstract = {Neovascular age-related macular degeneration (AMD), a leading cause of blindness, requires frequent intravitreal injection of antivascular endothelial growth factor (anti-VEGF), which could generate a succession of complications with poor patient compliance. The current VEGF-targeting therapies often fail in half of patients due to the complex pathologic microenvironment of excessive reactive oxygen species (ROS) production, and increased levels of inflammation are accompanied by choroidal neovascularization (CNV). We herein reported multifunctional nanotherapeutics featuring superior antioxidant and anti-inflammation properties that aim to reverse the pathological condition, alongside its strong targeted antiangiogenesis to CNV and its ability to provide long-term sustained bioactive delivery via the minimally invasive subconjunctival injection, so as to achieve satisfactory wet AMD treatment effects. Concretely, the nanomedicine was designed by coencapsulation of astaxanthin (AST), a red pigmented carotenoid known for its antioxidative, anti-inflammatory and antiapoptotic properties, and axitinib (AXI), a small molecule tyrosine kinase inhibitor that selectively targets the vascular epidermal growth factor receptor for antiangiogenesis, into the Food and Drug Administration (FDA) approved poly(lactic-co-glycolic acid) (PLGA), which forms the nanodrug of PLGA@AST/AXI. Our results demonstrated that a single-dose subconjunctival administration of PLGA@AST/AXI showed a rational synergistic effect by targeting various prevailing risk factors associated with wet AMD, ensuring persistent drug release profiles, maintaining good ocular biocompatibility, and causing no obvious mechanical damage. Such attributes are vital and hold significant potential in treating ocular posterior segment diseases. Moreover, this nanotherapeutic strategy represents a versatile and broad-spectrum nanoplatform, offering a promising alternative for the complex pathological progression of other neovascular diseases.},
}
@article {pmid39015241,
year = {2024},
author = {Hui, M and Gunzenhauser, R and Dillon, A and Tsui, I},
title = {Unexpected Vision Loss following Six Intravitreal Injections for Neovascular Age-Related Macular Degeneration.},
journal = {Case reports in ophthalmology},
volume = {15},
number = {1},
pages = {525-531},
pmid = {39015241},
issn = {1663-2699},
abstract = {INTRODUCTION: We present a case of a patient with preceding vitreomacular traction (VMT) who developed a full-thickness macular hole (FTMH) following his sixth intravitreal aflibercept injection for the treatment of age-related macular degeneration and review the literature on risk factors and pathogenesis of this adverse event.<br><br>CASE PRESENTATION: FTMH can occur after an extended number of repeat intravitreal injections in the setting of worsening vitreomacular adhesion or VMT. This patient's FTMH was successfully treated surgically in a timely manner, and additional injections were resumed safely.<br><br>CONCLUSIONS: Patients with an unexpected decrease in vision after intravitreal injections should be reevaluated with optical coherence tomography to rule out alternative pathology including vitreomacular interface abnormalities. FTMH, if present, should be treated promptly to allow for resumption of therapy as needed and visual optimization.},
}
@article {pmid39015234,
year = {2024},
author = {Tsui, JC and Aleman, TS and Tapino, PJ and Kim, BJ},
title = {Detailed Phenotype Supports Pathogenicity of Hypomorphic Variant in ABCC6-Associated Pattern Dystrophy.},
journal = {Case reports in ophthalmology},
volume = {15},
number = {1},
pages = {497-506},
pmid = {39015234},
issn = {1663-2699},
abstract = {INTRODUCTION: We report a case of pseudoxanthoma elasticum (PXE) with an atypical phenotype likely related to a hypomorphic variant in ABCC6.<br><br>CASE PRESENTATION: A 66-year-old Caucasian female with a history of a maculopathy interpreted as either age-related macular degeneration or a pattern dystrophy underwent a detailed ophthalmic evaluation. Visual acuities were 20/25, OD, and 20/20, OS. Spectral domain optical coherence and fluorescein angiography demonstrated outer retinal disruptions and breaks in retinal pigment epithelium (RPE)/Bruch's membrane bilaterally, consistent with angioid streaks. A large area of hypo- and hyperautofluorescence extending from the central retina into the peripapillary retina was documented with short-wavelength excitation autofluorescence. The area of hypoautofluorescence, which was much larger on near-infrared excitation, spared the temporal retina. Two-color dark-adapted perimetries documented severe rod sensitivity losses and less severe cone sensitivity abnormalities co-localizing with the RPE abnormalities. No obvious skin findings were observed, and initial dermatologic biopsy was negative. Gene screening identified a pathogenic ABCC6 gene variant c.1552C>T and a previously reported variant of uncertain significance c.1171A>G. A second dermatologic biopsy demonstrated positive findings consistent with PXE.<br><br>CONCLUSION: Although this patient had minimal skin findings, this patient had characteristic structural and functional abnormalities of a pattern dystrophy with angioid streaks and histologic evidence of PXE, suggesting compound heterozygous variants involving the hypomorphic ABCC6 c.1171A>G variant. These findings support the pathogenic role of both variants.},
}
@article {pmid39015229,
year = {2024},
author = {Angus, ZG and Ong, D and Wickremasinghe, SS},
title = {Fluorescein Angiogram Causing Cutaneous Venous Staining: A Rare Self-Resolving Phenomenon.},
journal = {Case reports in ophthalmology},
volume = {15},
number = {1},
pages = {548-551},
pmid = {39015229},
issn = {1663-2699},
abstract = {INTRODUCTION: Fluorescein angiography (FA) is a useful investigation in the diagnosis and treatment of retinal and choroidal disease. FA has well-reported adverse effects, most being mild. Very few cases have reported cutaneous venous staining following FA.<br><br>CASE PRESENTATION: Two cases are reported. Case 1 was a 90-year-old female with bilateral neovascular age-related macular degeneration. In the few minutes following her routine FA, she developed cutaneous fluorescein staining ascending along the superficial forearm veins proximal to the cannula in situ at the dorsal wrist. Case 2 was a 50-year-old male with diabetic macular oedema. In the minutes following his FA, he developed cutaneous fluorescein staining descending along the dorsal forearm veins distal to the cannula in situ at the cubital fossa. Both patients were managed conservatively with the stain resolving in the next few days.<br><br>CONCLUSION: Cutaneous fluorescein staining around superficial vasculature is a rare phenomenon. Despite this, it seems to be self-limiting and does not require any treatment.},
}
@article {pmid39015226,
year = {2024},
author = {Takamiya, M},
title = {The Management of Two Cases with Retinal Arterial Macroaneurysm by Anti-Vascular Endothelial Growth Factor.},
journal = {Case reports in ophthalmology},
volume = {15},
number = {1},
pages = {490-496},
pmid = {39015226},
issn = {1663-2699},
abstract = {INTRODUCTION: We report on one case of age-related macular degeneration and one case of diabetic macular edema with concomitant retinal arterial macroaneurysm (RAM) that were treated with anti-vascular endothelial growth factor (VEGF) intravitreal injections.<br><br>CASE PRESENTATION: Case 1 involved a 71-year-old woman with a 30-year history of diabetes who was undergoing dialysis. Pretreatment visual acuity in the right eye was 0.4. Fundus fluorescein angiography (FA) showed that numerous microaneurysms and RAM were located at a distance of two papillary diameters from the macular area. Diabetic macular edema was diagnosed. After 12 anti-VEGF injections, the macular edema resolved, microaneurysms decreased, and the RAM also disappeared. Visual acuity in the right eye improved to 0.7. Case 2 involved an 81-year-old woman receiving treatment for disorders including hypertension and dyslipidemia. Pretreatment visual acuity in the right eye was 0.03. And vitreous hemorrhage was present. After one ranibizumab intravitreal injection, the fundus became clearly visible. Macular subretinal hemorrhage and an RAM in the upper macula area were evident on FA and optical coherence tomography. After four intravitreal injections of ranibizumab, macular hemorrhage resolved, RAM disappeared, and visual acuity improved to 0.2. All cases were treated by intravitreal injection of anti-VEGF. After several injections, the macular hemorrhage or macular edema was resolved. RAM disappeared, and visual acuity improved.<br><br>CONCLUSION: Intravitreal injection of anti-VEGF appears effective for age-related macular degeneration or diabetic macular edema with concomitant RAM. Although anti-VEGF intravitreal injections are not covered by health insurance for the treatment of RAM, their effectiveness means that the expansion of indications is desirable.},
}
@article {pmid39013988,
year = {2024},
author = {Tanaka, F and Mino, T and Moriguchi, Y and Nagahama, H and Tamura, M and Oshima, Y and Akiba, M and Enaida, H},
title = {Developing quantitative analysis program of blood flow velocity according to vessel diameter for neovascular age-related macular degeneration using OCTA-VISTA.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {16352},
pmid = {39013988},
issn = {2045-2322},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Blood Flow Velocity ; Cross-Sectional Studies ; Retrospective Studies ; *Macular Degeneration/physiopathology/diagnostic imaging/pathology ; *Retinal Vessels/diagnostic imaging/physiopathology/pathology ; Middle Aged ; Aged, 80 and over ; Choroidal Neovascularization/diagnostic imaging/physiopathology/pathology ; Fluorescein Angiography/methods ; },
abstract = {This study aimed to develop a quantitative analysis program of blood flow velocity by vessel diameter in neovascular age-related macular degeneration (nAMD) subjects using high-speed swept-source optical coherence tomography angiography. This retrospective, observational, cross-sectional study included 10 eyes of healthy volunteers and 4 eyes of patients with representative nAMD. Novel scan patterns and variable interscan time analysis were utilized to measure the flow parameter, a surrogate marker of blood flow velocity, by vessel diameter within different depths. Detected vessels at superficial and deep as well as outer retinal regions were categorized into three vessel diameters (major vessels (> 40 μm), medium vessels (20-40 μm), and capillaries (< 20 μm)). The flow parameter increased with enlarged vessel diameter in all participants at superficial and deep layer. All nAMD subjects, except for type 3 macular neovascularization (MNV), contained a structure dominated by medium vessels at outer retinal region. The mean flow parameter at outer retinal region was type 1 MNV (1.46 ms[-1]), type 1 + 2 MNV (0.98 ms[-1]), and polypoidal choroidal vasculopathy, including branching vascular networks (1.46 ms[-1]). This program provides the possibility to extract the blood flow information at different depths by vessel diameter types, which is considered to be useful tool for evaluating nAMD pathology and activity.},
}
@article {pmid39013515,
year = {2024},
author = {Zhuang, X and Pu, J and Li, M and Mi, L and Zhang, X and Ji, Y and Zhang, Y and He, G and Chen, X and Zeng, Y and Su, Y and Gan, Y and Hao, X and Wen, F},
title = {Association between three-dimensional morphological features and functional indicators of neovascular age-related macular degeneration.},
journal = {Microvascular research},
volume = {155},
number = {},
pages = {104716},
doi = {10.1016/j.mvr.2024.104716},
pmid = {39013515},
issn = {1095-9319},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Fluorescein Angiography ; Imaging, Three-Dimensional ; Predictive Value of Tests ; Prospective Studies ; Time Factors ; Tomography, Optical Coherence ; Visual Acuity ; *Wet Macular Degeneration/physiopathology/diagnostic imaging/diagnosis ; },
abstract = {PURPOSE: To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This was a prospective observational study of treatment-na&#xef;ve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm[3]) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm[2]) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL).<br><br>RESULTS: Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P&#xa0;<&#xa0;0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (&#x3b2;&#xa0;=&#xa0;0.377, P&#xa0;<&#xa0;0.001), avascular SHRM (&#x3b2;&#xa0;=&#xa0;0.306, P&#xa0;=&#xa0;0.032), and ELM impairment area (&#x3b2;&#xa0;=&#xa0;0.301, P&#xa0;=&#xa0;0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (&#x3b2;&#xa0;=&#xa0;0.374, p&#xa0;=&#xa0;0.003; &#x3b2;&#xa0;=&#xa0;0.388, P&#xa0;<&#xa0;0.001, respectively), while ONL impairment primarily associated with MNV (&#x3b2;&#xa0;=&#xa0;0.475, P&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.},
}
@article {pmid39012703,
year = {2024},
author = {Mathis, T and Baudin, F and Mariet, AS and Augustin, S and Bricout, M and Przegralek, L and Roubeix, C and Benzenine, &#xc9; and Blot, G and Nous, C and Kodjikian, L and Mauget-Faÿsse, M and Sahel, JA and Plevin, R and Zeitz, C and Delarasse, C and Guillonneau, X and Creuzot-Garcher, C and Quantin, C and Hunot, S and Sennlaub, F},
title = {DRD2 activation inhibits choroidal neovascularization in patients with Parkinson's disease and age-related macular degeneration.},
journal = {The Journal of clinical investigation},
volume = {134},
number = {17},
pages = {},
pmid = {39012703},
issn = {1558-8238},
mesh = {Aged ; Animals ; Humans ; Male ; Mice ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; Dopamine Agonists/therapeutic use ; *Levodopa/adverse effects ; *Macular Degeneration/drug therapy/pathology ; Mice, Inbred C57BL ; *Parkinson Disease/drug therapy ; *Receptors, Dopamine D2/metabolism ; Retrospective Studies ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. l-DOPA-treated Parkinson's disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models that combine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced (MPTP-induced) PD and laser-induced nAMD with standard PD treatment of l-DOPA/DOPA-decarboxylase inhibitor or specific dopamine receptor inhibitors, we here demonstrate that l-DOPA treatment-induced increase of dopamine-mediated dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than 200,000 patients with nAMD receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2 agonist-treated PD patients have a significantly delayed age of onset of nAMD and reduced need for anti-VEGF therapies, similar to the effects of the l-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in patients with nAMD.},
}
@article {pmid39010943,
year = {2024},
author = {Borchert, GA and Shamsnajafabadi, H and Ng, BWJ and Xue, K and De Silva, SR and Downes, SM and MacLaren, RE and Cehajic-Kapetanovic, J},
title = {Age-related macular degeneration: suitability of optogenetic therapy for geographic atrophy.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1415575},
pmid = {39010943},
issn = {1662-4548},
abstract = {Age-related macular degeneration (AMD) is a growing public health concern given the aging population and it is the leading cause of blindness in developed countries, affecting individuals over the age of 55 years. AMD affects the retinal pigment epithelium (RPE) and Bruch's membrane in the macula, leading to secondary photoreceptor degeneration and eventual loss of central vision. Late AMD is divided into two forms: neovascular AMD and geographic atrophy (GA). GA accounts for around 60% of late AMD and has been the most challenging subtype to treat. Recent advances include approval of new intravitreally administered therapeutics, pegcetacoplan (Syfovre) and avacincaptad pegol (Iveric Bio), which target complement factors C3 and C5, respectively, which slow down the rate of enlargement of the area of atrophy. However, there is currently no treatment to reverse the central vision loss associated with GA. Optogenetics may provide a strategy for rescuing visual function in GA by imparting light-sensitivity to the surviving inner retina (i.e., retinal ganglion cells or bipolar cells). It takes advantage of residual inner retinal architecture to transmit visual stimuli along the visual pathway, while a wide range of photosensitive proteins are available for consideration. Herein, we review the anatomical changes in GA, discuss the suitability of optogenetic therapeutic sensors in different target cells in pre-clinical models, and consider the advantages and disadvantages of different routes of administration of therapeutic vectors.},
}
@article {pmid39009704,
year = {2024},
author = {Lee, SY and Cho, YK and Bae, CS and Kim, G and Lee, MJ and Cho, SS and Jeon, IC and Park, DH},
title = {Oxidative and carbonyl stress induced AMD and Codonopsis lanceolata ameliorates AMD via controlling oxidative and carbonyl stress.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {16322},
pmid = {39009704},
issn = {2045-2322},
support = {2022R1A5A8033794//the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ ; },
mesh = {*Codonopsis/chemistry ; Humans ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Oxidative Stress/drug effects ; *Apoptosis/drug effects ; *NF-E2-Related Factor 2/metabolism ; Plant Extracts/pharmacology ; Antioxidants/pharmacology ; Kelch-Like ECH-Associated Protein 1/metabolism ; Cell Line ; Aldehydes/pharmacology ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Light/adverse effects ; Proto-Oncogene Proteins c-bcl-2/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of blindness. AMD is currently incurable; the best solution is to prevent its occurrence. To develop drugs for AMD, it is crucial to have a model system that mimics the symptoms and mechanisms in patients. It is most important to develop safer and more effective anti-AMD drug. In this study, the dose of A2E and the intensity of blue light were evaluated to establish an appropriate atrophic in vitro model of AMD and anti-AMD effect and therapeutic mechanism of Codonopsis lanceolata. The experimental groups included a control group an AMD group treated with A2E and blue light, a lutein group treated with 25 μM lutein after AMD induction, and three groups treated with different doses of C. lanceolata (10, 20, and 50 μg/mL) after AMD induction. Intrinsic apoptotic pathway (Bcl-2 family), anti-oxidative system (Keap1/Nrf2/HO-1 antioxidant response element), and anti-carbonyl effect (4-hydroxynonenal [4-HNE]) were evaluated using immunofluorescence, MTT, TUNEL, FACS, and western blotting analyses. A2E accumulation in the cytoplasm of ARPE-19 cells depending on the dose of A2E. Cell viability of ARPE-19 cells according to the dose of A2E and/or blue light intensity. The population of apoptotic or necrotic cells increased based on the A2E dose and blue light intensity. Codonopsis lanceolata dose-dependently prevented cell death which was induced by A2E and blue light. The antiapoptotic effect of that was caused by activating Keap1/Nrf2/HO-1 pathway, suppressing 4-HNE, and modulating Bcl-2 family proteins like increase of antiapoptotic proteins such as Bcl-2 and Bcl-XL and decrease of proapoptotic protein such as Bim. Based on these findings, 30 μM A2E and 20 mW/cm[2] blue light on adult retinal pigment epithelium-19 cells was an appropriate condition for AMD model and C. lanceolata shows promise as an anti-AMD agent.},
}
@article {pmid39007849,
year = {2024},
author = {Cozzi, M and Casaluci, M and Ruggi, G and Airaldi, M and Romano, F and Bertoni, A and Green-Gomez, M and Nolan, JM and Staurenghi, G and Invernizzi, A},
title = {In Vivo Correlation Between Macular Pigment Optical Volume and Retinal Layers Thickness.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {23},
pmid = {39007849},
issn = {1552-5783},
mesh = {Humans ; Female ; Cross-Sectional Studies ; Male ; *Tomography, Optical Coherence/methods ; *Macular Pigment/metabolism ; Aged ; Middle Aged ; Adult ; Zeaxanthins/metabolism ; Retina/diagnostic imaging/metabolism/pathology ; Visual Acuity/physiology ; Macular Degeneration/metabolism/diagnosis ; Healthy Volunteers ; Lutein/metabolism ; Aged, 80 and over ; },
abstract = {PURPOSE: This study aims to investigate the potential in vivo relationship between macular pigment (MP) and retinal layers thickness in healthy subjects and dry, non-advanced age-related macular degeneration (AMD).<br><br>METHODS: An observational, cross-sectional study was conducted. Healthy subjects >40&#xa0;years and patients with early or intermediate AMD were recruited. Structural OCT and macular pigment optical volume (MPOV) were collected for each subject. Retinal layers parameters were calculated based on the standard early treatment diabetic retinopathy study (ETDRS) map. Additionally, MPOV within 1&#xb0;, 2&#xb0;, and 9&#xb0; of eccentricity was assessed and associated with retinal layers thickness and volume. Linear mixed-effects models were used to test the relationship between MP and structural OCT parameters, while adjusting for known possible confounding factors.<br><br>RESULTS: A total of 144 eyes of 91 subjects (60.4% females) were evaluated, comprising 43% normal eyes and 57% with early/intermediate AMD. Among the retinal layers, only the outer nuclear layer (ONL) thickness and volume appeared to be associated to higher MP levels. Specifically, the central ONL thickness was identified as a significant predictor of the MPOV 1&#xb0;(P = 0.04), while the parafoveal ONL thickness (inner ETDRS subfield) was identified as a significant fixed effect on the MPOV 9&#xb0; (P = 0.037). Age and the presence of drusen or subretinal drusenoid deposits were also tested without showing significant correlations.<br><br>CONCLUSIONS: Among the retinal layers examined, only the ONL thickness demonstrated a significant association with MPOV. Consequently, ONL thickness might serve as a potential biomarker related to MP levels.},
}
@article {pmid39006341,
year = {2024},
author = {Beuran, DI and Cornăcel, C and Tătaru, CP},
title = {Smartphone fundoscopy with 20 dioptres lens: our experience.},
journal = {Romanian journal of ophthalmology},
volume = {68},
number = {2},
pages = {148-151},
pmid = {39006341},
issn = {2501-2533},
mesh = {Humans ; *Smartphone ; *Ophthalmoscopy/methods ; *Fundus Oculi ; Retinal Diseases/diagnosis ; Male ; Female ; Equipment Design ; },
abstract = {Objective: Assessment of the utility of smartphone fundoscopy in diagnosing posterior pole pathologies. Methods: An iPhone 12 and a 20D Volk lens were used for smartphone fundoscopy. Patients needing bedside consultation were examined with direct ophthalmoscopy and smartphone fundoscopy. Some patients were examined with this technique after slit lamp examination. Results: Over one year 23 bedside fundus examinations were performed and 2 papilledema were diagnosed. After initial slit lamp examination, photos of various pathologies were taken: age-related macular degeneration, branch retinal artery occlusion, arterial embolus, branch retinal vein occlusion, non-arteritic anterior ischemic optic neuropathy, myelinated retinal nerve fiber layer, choroidal naevus. Discussion: With the 20D lens, the image is overturned, magnified 3,13X, and the field of view is 46°. The utility was demonstrated in literature by teaching students this technique and using it in screening for retinopathy of prematurity. The weighted retinal irradiance was measured in two studies. It was 4,6 mW/cm2 in one and from 0,58 to 2,30 mW/cm2 in the other, within safe limits. Conclusions: Smartphone fundoscopy is a fast, accessible, and safe technique for fundus examinations. Other departments could use it for the diagnosis of papilledema.},
}
@article {pmid39005302,
year = {2024},
author = {Gao, F and Tom, E and Rydz, C and Cho, W and Kolesnikov, AV and Sha, Y and Papadam, A and Jafari, S and Joseph, A and Ahanchi, A and Saraei, NBS and Lyon, D and Foik, A and Nie, Q and Grassmann, F and Kefalov, VJ and Skowronska-Krawczyk, D},
title = {Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Reversing Age-related Vision Decline.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39005302},
issn = {2692-8205},
support = {P30 EY034070/EY/NEI NIH HHS/United States ; T32 EY032448/EY/NEI NIH HHS/United States ; R01 EY035137/EY/NEI NIH HHS/United States ; F30 EY035146/EY/NEI NIH HHS/United States ; U01 EY034594/EY/NEI NIH HHS/United States ; },
abstract = {The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD). ELOVL2 (Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently the best predictor of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2 [C234W]) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals significantly improved visual function and reduced accumulation of ApoE, HTRA1 and complement proteins in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature of younger retina. Finally, we present the first human genetic data showing significant association of several variants in the human ELOVL2 locus with the onset of intermediate AMD, underlying the translational significance of our findings. In sum, our study identifies novel therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.},
}
@article {pmid39004382,
year = {2024},
author = {Karmoker, JR and Bounds, SE and Cai, J},
title = {Aryl hydrocarbon receptor (AhR)-mediated immune responses to degeneration of the retinal pigment epithelium.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1870},
number = {7},
pages = {167351},
pmid = {39004382},
issn = {1879-260X},
support = {P30 EY021725/EY/NEI NIH HHS/United States ; R01 EY034742/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Basic Helix-Loop-Helix Transcription Factors/metabolism/immunology/genetics ; Choroid/immunology/pathology/metabolism ; *Interleukin-17/metabolism/immunology ; Intraepithelial Lymphocytes/immunology/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; *Receptors, Aryl Hydrocarbon/metabolism/immunology/genetics ; Retinal Degeneration/immunology/pathology/metabolism ; *Retinal Pigment Epithelium/immunology/metabolism/pathology ; Signal Transduction/immunology ; },
abstract = {Injuries to the retinal pigment epithelium (RPE) trigger immune responses, orchestrating interactions within the innate and adaptive immune systems in the outer retina and choroid. We previously reported that interleukin 17 (IL-17) is a pivotal signaling molecule originating from choroidal γδ T cells, exerting protective effects by mediating functional connections between the RPE and subretinal microglia. In this current study, we generated mice with aryl hydrocarbon receptor (AhR) knockout specifically in IL-17-producing cells. These animals had deficiency in IL-17 production from γδ T cells, and exhibited increased sensitivity to both acute and chronic insults targeting the RPE. These findings imply that IL-17 plays a crucial role as a signaling cytokine in preserving the homeostasis of the outer retina and choroid.},
}
@article {pmid39004074,
year = {2024},
author = {Reitblat, O and Velleman, DA and Levy, A and Assia, EI and Kleinmann, G},
title = {Performance of Extended Depth of Focus Intraocular Lens in Eyes with Preexisting Retinal Disease.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {4},
pages = {241-250},
pmid = {39004074},
issn = {1423-0267},
mesh = {Humans ; Female ; *Visual Acuity ; Retrospective Studies ; Male ; Aged ; *Lenses, Intraocular ; Middle Aged ; *Retinal Diseases/physiopathology/surgery/diagnosis ; *Prosthesis Design ; *Depth Perception/physiology ; Follow-Up Studies ; Patient Satisfaction ; Refraction, Ocular/physiology ; Surveys and Questionnaires ; Lens Implantation, Intraocular/methods ; Pseudophakia/physiopathology ; Aged, 80 and over ; Phacoemulsification/methods ; Adult ; },
abstract = {INTRODUCTION: Extended depth of focus (EDOF) intraocular lens (IOL) offers improved near and intermediate vision, aiming to reduce spectacle dependence in cataract patients. This research aimed to evaluate the performance of EDOF IOL in patients with retinal pathologies following cataract surgery.<br><br>METHODS: The medical charts of thirty-three eyes with retinal pathologies and 100 healthy eyes that underwent cataract extraction with implantation of an EDOF IOL and had at least 3 weeks of postoperative follow-up were retrospectively included. Patients' overall satisfaction, spectacle dependence, visual perception, and side effects were evaluated with a self-reported questionnaire.<br><br>RESULTS: Mean uncorrected visual acuities (LogMAR) were significantly better in the healthy eyes compared with the eyes with retinal pathologies: 0.05 and 0.10, p = 0.011 (distance), 0.06 and 0.16, p = 0.001 (intermediate), and 0.20 and 0.28, p = 0.026 (near), respectively. No or rare use of spectacles for any distance was reported by 71% and 38% of patients, respectively (p = 0.004). Haloes/glare were reported by 17% and 23%, respectively (p = 0.556); only in 7% and 4% it was clinically disturbing (p > 0.999). The same IOL would be chosen again in 77% and 73% of patients, respectively, (p = 0.550).<br><br>CONCLUSION: Patients with retinal pathologies who were implanted with an EDOF IOL demonstrated excellent distant uncorrected visual results with reasonable intermediate and near uncorrected visual results alongside high satisfaction; however, results were inferior to those of the control healthy eyes.},
}
@article {pmid39002965,
year = {2024},
author = {Dave, S and Rathore, M and Campbell, P and Edgar, DF and Crabb, DP and Callaghan, T and Jones, PR},
title = {Views and opinions of patients with glaucoma and age-related macular degeneration on vision home-monitoring: a UK-based focus group study.},
journal = {BMJ open},
volume = {14},
number = {7},
pages = {e080619},
pmid = {39002965},
issn = {2044-6055},
mesh = {Humans ; *Focus Groups ; Female ; *Glaucoma/diagnosis ; Male ; *Macular Degeneration ; Aged ; *Qualitative Research ; Middle Aged ; Aged, 80 and over ; United Kingdom ; Surveys and Questionnaires ; Visual Acuity ; Visual Fields ; },
abstract = {OBJECTIVE: To investigate the views, hopes and concerns of patients living with glaucoma and age-related macular degeneration (AMD) regarding vision home-monitoring.<br><br>DESIGN: Qualitative study using focus groups and questionnaires. Participants were given three disease-relevant home-monitoring tests to try. The tests consisted of three visual field tests for the glaucoma groups (Melbourne Rapid Fields, Eyecatcher, Visual Fields Fast) and three acuity and/or contrast-sensitivity tests for AMD groups (Alleye, PopCSF, SpotChecks). Focus group data were thematically analysed.<br><br>SETTING: University meeting rooms in London, UK.<br><br>PARTICIPANTS: Eight people with glaucoma (five women, median age 74) and seven people with AMD (four women, median age 77) volunteered through two UK-based charities. Participants were excluded if they did not self-report a diagnosis of glaucoma or AMD or if they lived further than a 1-hour travel distance from the university (to ensure minimal travel burden on participants).<br><br>RESULTS: Six themes emerged from focus groups, the two most frequently referenced being: 'concerns about home-monitoring' and 'patient and practitioner access to results'. Overall, participants believed home-monitoring could provide patients with a greater sense of control, but also expressed concerns, including: the possibility of home-monitoring replacing face-to-face appointments; the burden placed on clinicians by the need to process additional data; struggles to keep up with requisite technologies; and potential anxiety from seeing worrying results. Most devices were scored highly for usability, though several practical improvements were suggested.<br><br>CONCLUSION: Patients with mild-to-moderate glaucoma/AMD expect vision home-monitoring to be beneficial, but have significant concerns about its potential implementation.},
}
@article {pmid39002821,
year = {2024},
author = {Ma, SZ and Dong, S and Zhou, ZY and Ji, XY and Zhang, YY and Wang, XQ and Zhang, B},
title = {The protective role of Cordyceps cicadae and its active ingredient myriocin against sodium iodate-induced age-related macular degeneration via an anti-necroptotic TNF-RIPK1/3 pathway.},
journal = {Journal of ethnopharmacology},
volume = {334},
number = {},
pages = {118565},
doi = {10.1016/j.jep.2024.118565},
pmid = {39002821},
issn = {1872-7573},
mesh = {Animals ; *Macular Degeneration/drug therapy ; *Cordyceps/chemistry ; Mice ; *Tumor Necrosis Factor-alpha/metabolism ; *Iodates ; *Retinal Pigment Epithelium/drug effects/metabolism ; Signal Transduction/drug effects ; Humans ; Cell Line ; Mice, Inbred C57BL ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Male ; Necroptosis/drug effects ; Fatty Acids, Monounsaturated ; },
abstract = {Cordyceps cicadae (C.cicadae), named "Chan Hua", an anamorph of Isaria cicadae Miquel, is an entomogenous complex formed by fungi parasitizing on the larvae of cicadas and belongs to the Claviciptaceae family and the genus Codyceps, which traditionally holds a significant place in Chinese ethnopharmacology, specifically for eye clarity and as a remedy for age-related ocular conditions. The underlying mechanisms contributing to its eyesight enhancement and potential effectiveness against Age-related macular degeneration (AMD) remain unexplored.<br><br>AIM OF THE STUDY: This study aims to elucidate the protective role of C.cicadae and its active ingredient, Myriocin (Myr), against AMD.<br><br>MATERIALS AND METHODS: A chemical inducer was employed to make retinal pigment epithelium (RPE) damage in vitro and in vivo. The key ingredients of C.cicadae and their related mechanisms for anti-AMD were studied through bioinformatic analysis and molecular biological approaches.<br><br>RESULTS: Myr was identified through high-performance liquid chromatography (HPLC) as an active ingredient in C.cicadae, and demonstrated a protective effect on RPE cells, reducing the structural damage and cell death induced by sodium iodate (SI). Further, Myr reduced eyelid secretions in AMD mice and restored their retinal structure and function. The differentially expressed genes (DEGs) in Myr treatment are primarily associated with TNF and Necroptosis signaling pathways. Molecular docking indicated a strong affinity between TNF and Myr. Myr inhibited the TNF signaling pathway thereby reducing the expression of inflammatory factors in ARPE-19&#xa0;cells. Additionally, Myr had consistent action with the necroptosis inhibitor Necrostatin-1 (Nec-1), inhibited the RIPK1/RIPK3/MLKL pathway thereby protecting ARPE-19&#xa0;cells.<br><br>CONCLUSION: The findings present Myr, as a potent protector against SI-induced AMD, predominantly through modulation of the TNF-RIPK1/RIPK3/MLKL signaling pathway, offering the insights of therapeutic C.cicadae as viable candidates for AMD treatment.},
}
@article {pmid39001799,
year = {2025},
author = {Gabilan, C and Belliere, J and Moranne, O and Pfirmann, P and Samson, M and Delattre, V and Thoreau, B and Gueutin, V and Boyer, A and Leurs, A and Astouati, Q and Ronsin, C and Quemeneur, T and Ribes, D and Karras, A and Faguer, S},
title = {Avacopan for anti-neutrophil cytoplasm antibodies-associated vasculitis: a multicentre real-world study.},
journal = {Rheumatology (Oxford, England)},
volume = {64},
number = {4},
pages = {2214-2219},
doi = {10.1093/rheumatology/keae359},
pmid = {39001799},
issn = {1462-0332},
support = {//Sanofi-Genzyme/ ; //AstraZeneca/ ; },
mesh = {Humans ; *Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy ; Male ; Aged ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Aged, 80 and over ; Rituximab/therapeutic use ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Antineutrophil Cytoplasmic ; Glucocorticoids/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Aniline Compounds ; Nipecotic Acids ; },
abstract = {OBJECTIVES: Avacopan, a selective C5aR1 inhibitor, recently emerged as a glucocorticoid (GCs) sparing agent in anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis (AAV). We aim to evaluate the tolerance and efficacy of avacopan given outside randomized clinical trials or with severe kidney involvement.<br><br>METHODS: In this multicentre retrospective study, we reviewed the clinical charts of patients with AAV and contraindication to high dose of GCs who received avacopan 30&#x2009;mg b.i.d plus standard-of-care regimen owing to the French early access program between 2020 and 2023. Efficacy and safety data were recorded using a standardized case report form.<br><br>RESULTS: Among the 31 patients (median age 72&#x2009;years), 10 had a relapsing AAV, 20 had anti-myeloperoxidase antibodies and 30 had kidney vasculitis. Induction regimen included rituximab (n&#x2009;=&#x2009;27), cyclophosphamide (n&#x2009;=&#x2009;2) or both (n&#x2009;=&#x2009;2). Five patients did not receive GCs. Despite rapid GCs tapering (which were withdrawn in 23 patients before month 3), 25 patients (81%) had a favourable outcome and no severe adverse event. The estimated glomerular filtration rate increased from 19 [15; 34] to 35&#x2009;mL/min/1.73&#x2009;m2 [23; 45] at month 12 (P < 0.05), independently of kidney biopsies findings. One patient developed refractory AAV and two had a relapse while receiving avacopan. At month 12, ANCA remained positive in 10/18 patients (55.5%). Two patients developed severe adverse events leading to a withdrawal of avacopan (hepatitis and age-related macular degeneration).<br><br>CONCLUSIONS: The GCs' sparing effect of avacopan was confirmed, even in patients with severe kidney vasculitis, but further studies are required to identify the optimal dosing of GCs when avacopan is used.},
}
@article {pmid39001285,
year = {2024},
author = {Ahn, SJ and Kim, YH},
title = {Clinical Applications and Future Directions of Smartphone Fundus Imaging.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {13},
pages = {},
pmid = {39001285},
issn = {2075-4418},
abstract = {The advent of smartphone fundus imaging technology has marked a significant evolution in the field of ophthalmology, offering a novel approach to the diagnosis and management of retinopathy. This review provides an overview of smartphone fundus imaging, including clinical applications, advantages, limitations, clinical applications, and future directions. The traditional fundus imaging techniques are limited by their cost, portability, and accessibility, particularly in resource-limited settings. Smartphone fundus imaging emerges as a cost-effective, portable, and accessible alternative. This technology facilitates the early detection and monitoring of various retinal pathologies, including diabetic retinopathy, age-related macular degeneration, and retinal vascular disorders, thereby democratizing access to essential diagnostic services. Despite its advantages, smartphone fundus imaging faces challenges in image quality, standardization, regulatory considerations, and medicolegal issues. By addressing these limitations, this review highlights the areas for future research and development to fully harness the potential of smartphone fundus imaging in enhancing patient care and visual outcomes. The integration of this technology into telemedicine is also discussed, underscoring its role in facilitating remote patient care and collaborative care among physicians. Through this review, we aim to contribute to the understanding and advancement of smartphone fundus imaging as a valuable tool in ophthalmic practice, paving the way for its broader adoption and integration into medical diagnostics.},
}
@article {pmid39000471,
year = {2024},
author = {Nicolini, G and Casini, G and Posarelli, C and Amato, R and Lulli, M and Balzan, S and Forini, F},
title = {Thyroid Hormone Signaling in Retinal Development and Function: Implications for Diabetic Retinopathy and Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {25},
number = {13},
pages = {},
pmid = {39000471},
issn = {1422-0067},
mesh = {Humans ; *Diabetic Retinopathy/metabolism/etiology/pathology ; *Macular Degeneration/metabolism/pathology ; *Thyroid Hormones/metabolism ; *Retina/metabolism/pathology ; *Signal Transduction ; Animals ; },
abstract = {Thyroid Hormones (THs) play a central role in the development, cell growth, differentiation, and metabolic homeostasis of neurosensory systems, including the retina. The coordinated activity of various components of TH signaling, such as TH receptors (THRs) and the TH processing enzymes deiodinases 2 and 3 (DIO2, DIO3), is required for proper retinal maturation and function of the adult photoreceptors, Müller glial cells, and pigmented epithelial cells. Alterations of TH homeostasis, as observed both in frank or subclinical thyroid disorders, have been associated with sight-threatening diseases leading to irreversible vision loss i.e., diabetic retinopathy (DR), and age-related macular degeneration (AMD). Although observational studies do not allow causal inference, emerging data from preclinical models suggest a possible correlation between TH signaling imbalance and the development of retina disease. In this review, we analyze the most important features of TH signaling relevant to retinal development and function and its possible implication in DR and AMD etiology. A better understanding of TH pathways in these pathological settings might help identify novel targets and therapeutic strategies for the prevention and management of retinal disease.},
}
@article {pmid39000382,
year = {2024},
author = {Kaštelan, S and Nikuševa-Martić, T and Pašalić, D and Antunica, AG and Zimak, DM},
title = {Genetic and Epigenetic Biomarkers Linking Alzheimer's Disease and Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {25},
number = {13},
pages = {},
pmid = {39000382},
issn = {1422-0067},
mesh = {Humans ; *Alzheimer Disease/genetics/metabolism/pathology ; *Macular Degeneration/genetics/metabolism/pathology ; *Epigenesis, Genetic ; *Biomarkers/metabolism ; Animals ; Genetic Predisposition to Disease ; Retina/metabolism/pathology ; },
abstract = {Alzheimer's disease (AD) represents a prominent neurodegenerative disorder (NDD), accounting for the majority of dementia cases worldwide. In addition to memory deficits, individuals with AD also experience alterations in the visual system. As the retina is an extension of the central nervous system (CNS), the loss in retinal ganglion cells manifests clinically as decreased visual acuity, narrowed visual field, and reduced contrast sensitivity. Among the extensively studied retinal disorders, age-related macular degeneration (AMD) shares numerous aging processes and risk factors with NDDs such as cognitive impairment that occurs in AD. Histopathological investigations have revealed similarities in pathological deposits found in the retina and brain of patients with AD and AMD. Cellular aging processes demonstrate similar associations with organelles and signaling pathways in retinal and brain tissues. Despite these similarities, there are distinct genetic backgrounds underlying these diseases. This review comprehensively explores the genetic similarities and differences between AMD and AD. The purpose of this review is to discuss the parallels and differences between AMD and AD in terms of pathophysiology, genetics, and epigenetics.},
}
@article {pmid38999967,
year = {2024},
author = {Vilkeviciute, A and Cebatoriene, D and Kriauciuniene, L and Zaliuniene, D and Liutkeviciene, R},
title = {Exudative Age-Related Macular Degeneration: Association between Treatment Efficacy and Single-Nucleotide Variants in RAD51B, TRIB1, COL8A1, COL10A1, IL-9, IL-10, and VEGFA Genes.},
journal = {International journal of molecular sciences},
volume = {25},
number = {13},
pages = {},
pmid = {38999967},
issn = {1422-0067},
support = {S-MIP-23-96//The Research Council of Lithuania under the initiative of Researcher Group Projects./ ; },
mesh = {Humans ; *Polymorphism, Single Nucleotide ; *Vascular Endothelial Growth Factor A/genetics ; Male ; Female ; Aged ; *Interleukin-10/genetics ; *Intracellular Signaling Peptides and Proteins/genetics ; *Protein Serine-Threonine Kinases/genetics/antagonists &amp; inhibitors ; *Interleukin-9/genetics ; *Collagen Type X/genetics ; Treatment Outcome ; Macular Degeneration/genetics/drug therapy/pathology ; Aged, 80 and over ; DNA-Binding Proteins/genetics ; Middle Aged ; Genotype ; Collagen Type VIII ; },
abstract = {Age-related macular degeneration (AMD) is a progressive neurodegenerative condition leading to vision loss and eventual blindness, with exudative AMD posing a heightened risk due to choroidal neovascularization and localized edema. Therapies targeting the VEGF pathway aim to address this mechanism for treatment effectiveness. Our study aimed to evaluate associations between specific genetic variants (RAD51B rs8017304, rs2588809; TRIB1 rs6987702, rs4351379; COL8A1 rs13095226; COL10A1 rs1064583; IL-9 rs1859430, rs2069870, rs11741137, rs2069885, rs2069884; IL-10 rs1800871, rs1800872, rs1800896; VEGFA rs1570360, rs699947, rs3025033, rs2146323) and the response to anti-VEGF treatment for exudative AMD. We enrolled 119 patients with exudative AMD categorized as responders or non-responders based on their response to anti-VEGF treatment. Statistical analysis revealed that RAD51B rs8017304 heterozygous and homozygous minor allele carriers had increased CMT before treatment compared to wild-type genotype carriers (p = 0.004). Additionally, TRIB1 rs4351379 heterozygous and homozygous minor allele carriers exhibited a greater decrease in central macular thickness (CMT) after 6 months of treatment than wild-type genotype carriers (p = 0.030). IL-9 rs1859430, rs2069870, and rs2069884 heterozygous and homozygous minor allele carriers had worse BCVA before treatment than wild-type genotype carriers (p = 0.018, p = 0.012, p = 0.041, respectively). Conversely, IL-9 rs2069885 heterozygous and homozygous minor allele carriers showed greater improvement in BCVA after 6 months compared to wild-type genotype carriers (p = 0.032). Furthermore, VEGFA rs699947 heterozygous and homozygous minor allele carriers had better BCVA before treatment and after 3 and 6 months of treatment than wild-type genotype carriers (p = 0.003, p = 0.022, respectively), with these carriers also exhibiting higher CMT after 6 months of anti-VEGF treatment (p = 0.032). Not all results remained statistically significant under this stringent correction for multiple comparisons. The comparisons of the serum concentrations of IL-10, VEGF-A, and VEGF-R2/KDR between non-responders and responders did not yield statistically significant differences. Our study identified significant associations between genetic variants, including RAD51B rs8017304, TRIB1 rs4351379, IL-9 rs1859430, rs2069870, rs2069884, rs2069885, and VEGFA rs699947, and parameters related to the efficacy of exudative AMD treatment, such as BCVA and CMT.},
}
@article {pmid38999523,
year = {2024},
author = {Kohlhas, P and Abdin, AD and Aljundi, W and Mattern, AI and Devenijn, M and Borchert, K and Fricke, A and Viering, T and Wasem, J and Seitz, B and Kaymak, H},
title = {Natural History of Visual Acuity and Microperimetry-Based Functional Outcome Measures of the Macula in Patients with Geographic Atrophy: A Retrospective Chart Review Study in Germany.},
journal = {Journal of clinical medicine},
volume = {13},
number = {13},
pages = {},
pmid = {38999523},
issn = {2077-0383},
abstract = {Background/Objectives: Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) leading to the progressive and irreversible loss of visual function. Characteristics of GA include atrophic lesions resulting from the loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. During GA progression, atrophic lesions typically advance from the macular periphery to the center, affecting foveal light sensitivity and visual acuity. This study analyzed changes in light sensitivity and visual acuity during the natural course of GA progression using the topographic analysis of structural and functional changes based on Early Treatment Diabetic Retinopathy Study (ETDRS) charts, multimodal imaging, and microperimetry assessment. Methods: Medical chart data of GA patients between 2014 and 2022 from the Internationale Innovative Ophthalmochirurgie GbR (I.I.O.) research center (Düsseldorf, Germany) were retrospectively analyzed. All patient eyes fulfilling the phase 3 OAKS study inclusion criteria were included and followed up for 60 months. The imputation of missing measurements and dropouts was performed by linear mixed models. Results: A total of 20 GA eyes from 13 GA patients were included in the study. At the index, 53.8% of patients had bilateral GA, with 70.0% of the eyes showing multifocal GA and 30.0% subfoveal encroachment (SFE). A total of 35.0% of the eyes had 2-5, and 15.0% over 20, areas of atrophy. Over time, the GA lesion size increased from 6.4 mm[2] to 11.8 mm[2] (1.08 mm[2]/year). After an average observation time of 2.9 years, 78.6% of the initially unaffected study eyes developed SFE. The percentage of study eyes without visual impairment decreased from 55.0% to 30.0%, with mean normal-luminance best-corrected visual acuity (NL-BCVA) reducing from 63.7 to 55.7 ETDRS letters. The share of absolute scotoma points in microperimetry assessment increased from 15.7% to 43.5% while overall average macular sensitivity declined from 15.7 dB to 7.4 dB. Conclusions: The substantial deterioration of macular outcomes and visual function was comprehensively detected. The results were a documentation of structural and functional aspects of the natural progression of GA for a 60-month follow-up, providing a typical outline for AMD patients with GA.},
}
@article {pmid38999484,
year = {2024},
author = {Håman, L and Källstrand, J and Carlsson, IM and Ivarsson, A and Kristén, L and Lindgren, EC},
title = {An Empowerment-Based Physical Activity Intervention for Older People with Advanced Age-Related Macular Degeneration: An Exploratory Qualitative Case Study Design.},
journal = {Journal of clinical medicine},
volume = {13},
number = {13},
pages = {},
pmid = {38999484},
issn = {2077-0383},
support = {NYPS-20293225//Interreg &#xd6;resund-Kattegat-Skagerrak European Regional Development Fund/ ; F 2020/111//School of Health andWelfare, Halmstad University/ ; },
abstract = {Background: Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment and impacts daily life. There are benefits of physical activity for people who are affected with AMD; however, living with AMD is associated with lower levels of physical activity and social isolation. The aim of this study was to explore how older people with AMD in Sweden experienced participation in a 6-month empowerment-based physical activity intervention and how it influenced their physical abilities. Methods: The participants were nine individuals with AMD aged 70-87 years. The intervention comprised physical and social activities in a group twice a week and individual health coaching on three occasions. The study was based on an exploratory qualitative case study design. Results: The findings showed two themes: created meaningfulness in life and creative and playful ways to develop body movements. The findings also showed improved muscle strength after the intervention. Conclusions: The findings showed that participants had increased social connectedness, improved physical self-efficacy and physical ability, as well as improved muscle strength. The empowerment process of the intervention was appreciated by the participants and challenged them to participate in physical activity offered by the municipality for older individuals.},
}
@article {pmid38999398,
year = {2024},
author = {Seredyka-Burduk, M and Liberski, S and Malukiewicz, G and Kocięcki, J and Kaluzny, BJ},
title = {Cataract Surgery in nAMD Patients Receiving Intravitreal Aflibercept Injections.},
journal = {Journal of clinical medicine},
volume = {13},
number = {13},
pages = {},
pmid = {38999398},
issn = {2077-0383},
abstract = {Background: To evaluate functional and anatomical outcomesof cataract surgery in neovascular age-related macular neovascularization (nAMD) eyes receiving anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections in modified pro re nata (PRN) regimen. Materials and Methods: Sixty eyes of 60 nAMD patients, including 41 women (68.3%) and 19 men (31.7%) in an average age of 77.35 ± 6.41 years, under treatment with intravitreal aflibercept injections in modified PRN regimen with no signs of macular neovascularization (MNV) activity during two consecutive visits were included in this prospective, observational study. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), as well as the number of anti-VEGF injections were monitored six months before and after phacoemulsification with intraocular lens (IOL) implantation. Further, the change of the abovementioned parameters was assessed during the six-month follow-up period for CRT and the number of injections, while the BCVA was monitored for 54 months. Results: BCVA measured on the first day after surgery (0.17 ± 0.19 logMAR) as well as in the six-month post-surgery (0.13 ± 0.16 logMAR) significantly improved compared to preop values (0.42 ± 0.20 logMAR). BCVA remains stable during the observational period. We found that both differences were statistically significant (p < 0.01). The mean CRT and the mean number of injections did not differ between the six-month pre- and post-surgical periods. Conclusions: We showed the beneficial effect of phacoemulsification in nAMD patients treated with anti-VEGF agents on visual outcomes in the short and long term. Cataract surgery in nAMD eyes treated with anti-VEGF injections does not increase the frequency of anti-VEGF injections and does not cause deterioration of the macular status.},
}
@article {pmid38999321,
year = {2024},
author = {Kamao, H and Mitsui, E and Date, Y and Goto, K and Mizukawa, K and Miki, A},
title = {Clinical Characteristics of Unilateral Macular Neovascularization Patients with Pachydrusen in the Fellow Eye.},
journal = {Journal of clinical medicine},
volume = {13},
number = {13},
pages = {},
pmid = {38999321},
issn = {2077-0383},
abstract = {Background/Objectives: To approach the clinical properties of pachydrusen that differ from conventional drusen, we investigated the incidence of macular neovascularization (MNV) in fellow eyes and the treatment outcomes of intravitreal aflibercept (IVA) in MNV eyes of unilateral MNV patients with pachydrusen in the fellow eye. Methods: We retrospectively studied 261 consecutive patients with treatment-naïve unilateral MNV. Patients were classified into four groups according to the type of drusen in the fellow eye: the pachydrusen group (n = 49), the soft drusen group (n = 63), the subretinal drusenoid deposit (SDD) group (n = 24), and the no drusen group (n = 125). The development of the MNV in the fellow eye was evaluated for five years, and the retreatment proportion after three monthly aflibercept injections was evaluated for one year. Results: The choroidal thickness in the fellow eyes and MNV eyes was the greatest in the pachydrusen group (all p < 0.001). The 5-year incidence of MNV in the pachydrusen group was similar to that in the soft drusen group and no drusen group. The pachydrusen group had a lower retreatment rate than the other groups did (pachydrusen group: 46.4%; soft drusen group: 78.1%; SDDs: 87.5%; no drusen group: 83.3%). Conclusions: Unilateral MNV patients with pachydrusen in the fellow eye had a lower retreatment rate (46.4%/1 year); therefore, aflibercept monotherapy using the PRN regimen is one of the preferred treatment methods for MNV patients with pachydrusen in the fellow eye.},
}
@article {pmid38997766,
year = {2024},
author = {Nasimi, N and Nasimi, S and Grauslund, J and Vergmann, AS and Subhi, Y},
title = {Real-world efficacy of intravitreal faricimab for neovascular age-related macular degeneration: a systematic review.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {48},
pmid = {38997766},
issn = {2056-9920},
abstract = {BACKGROUND: To systematically review the real-world outcomes of intravitreal faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) to evaluate its efficacy and safety in clinical settings. This study was conducted due to the need for real-world evidence to complement the findings from controlled clinical phase-III trials.<br><br>METHODS: A systematic literature search was conducted on March 17, 2024, across 11 databases, utilizing search terms specifically tailored each database. All studies were reviewed qualitatively with specific focus on the outcomes of interest: the best-corrected visual acuity (BCVA), the central retina thickness (CRT), and the burden of therapy.<br><br>RESULTS: We identified a total of 22 eligible studies of 1762 eyes from 1618 patients with nAMD. Studies reported that intravitreal faricimab injections maintained BCVA in patients with previously treated eyes and demonstrated statistically significant improvement in patients with treatment-na&#xef;ve eyes. The CRT was reduced after intravitreal faricimab therapy. Faricimab was well-tolerated, with no significant safety concerns identified, and reduced the overall burden of therapy.<br><br>CONCLUSION: Real-world studies corroborate the conclusions drawn from phase-III trials regarding faricimab treatment, demonstrating improvement in both visual and anatomical outcomes. Additionally, no significant safety issues were identified, as the treatment was generally well-tolerated and reduced the overall burden of therapy in the real-world settings.},
}
@article {pmid38996902,
year = {2024},
author = {Voisin, A and Pénaguin, A and Gaillard, A and Leveziel, N},
title = {RNASeq profiling of retinal pigment epithelial cells derived from induced pluripotent stem cells revealed 3 genes involved in lipid homeostasis in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {246},
number = {},
pages = {109999},
doi = {10.1016/j.exer.2024.109999},
pmid = {38996902},
issn = {1096-0007},
mesh = {Cell Line ; *Homeostasis/genetics ; *Induced Pluripotent Stem Cells/cytology/metabolism ; *Lipid Metabolism/genetics ; *Macular Degeneration/genetics/metabolism/pathology ; *Retinal Pigment Epithelium/cytology/metabolism ; RNA-Seq ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is characterized by visual impairment observed in elderly population. Two forms of the disease are generally described, the atrophic (AMDa) and exudative forms (AMDe). Up until now, no curative treatment is available for this disease. The retinal pigment epithelium (RPE) plays a central role in the pathogenesis of age-related macular degeneration. Here, involvement of RPE dysfunction in AMD onset and progression was analyzed by a comparison of transcriptome profiles of hiPSC-RPE derived from healthy individuals or individuals affected by AMDa or AMDe. The analysis highlighted almost 1000 genes differentially expressed between the three comparison groups. Among these genes, 33 genes were already known to be involved in AMD pathogenesis. To establish an AMD genetic signature, we focused on genes differentially expressed in both AMDa/e cell lines compared to control cells and focused on the three genes (ABCA1, RPN2, RB1CC1) that were related to lipidic homeostasis. Differences in level expression of these three genes are found not only in control and AMDa/e cell lines, but also between AMDa and AMDe populations.},
}
@article {pmid38996175,
year = {2024},
author = {Elhalag, RH and Mohamed, MS and Abowafia, M and Mourid, MR and Mahmoud, N and Abourady, Y and Ghali, P and Moussa, MH and Shah, J and Motawea, KR},
title = {The role of oral metformin in preventing and treating age-related macular degeneration: A meta-analysis.},
journal = {Medicine},
volume = {103},
number = {28},
pages = {e38728},
pmid = {38996175},
issn = {1536-5964},
mesh = {*Metformin/therapeutic use/administration &amp; dosage ; Humans ; *Macular Degeneration/drug therapy/prevention &amp; control ; *Hypoglycemic Agents/therapeutic use/administration &amp; dosage ; Administration, Oral ; },
abstract = {BACKGROUND: We aimed to perform a meta-analysis to evaluate the effect of metformin on age-related macular degeneration.<br><br>METHODS: We searched the following databases: PubMed, Scopus, and Web of Science. We included any randomized control trials, prospective and retrospective cohorts, cross-sectional studies, and case-control studies that investigated the effect of metformin on age-related macular degeneration in our meta-analysis with no age or language restrictions. Review manager software, version 5.4 was used to perform the meta-analysis.<br><br>RESULTS: Ten studies were included in the meta-analysis with 1,447,470 patients included in the analysis. The pooled analysis showed no statistically significant difference between the metformin group and the non-metformin group regarding age-related macular degeneration (odds ratio [OR]&#x2005;=&#x2005;0.37, confidence interval [CI]&#x2005;=&#x2005;(0.14-1.02), P&#x2005;=&#x2005;.05). Subgroup analysis showed no statistically significant difference between metformin group and non-metformin group regarding age-related macular degeneration in present or past metformin usage (OR&#x2005;=&#x2005;0.19, CI&#x2005;=&#x2005;(0.03-1.1), P&#x2005;=&#x2005;.06), (OR&#x2005;=&#x2005;0.61, CI&#x2005;=&#x2005;(0.25-1.45), P&#x2005;=&#x2005;.26), respectively, The pooled analysis showed no statistically significant difference between age-related macular degeneration group and control group regarding metformin usage (OR&#x2005;=&#x2005;0.86, CI&#x2005;=&#x2005;(0.74-1.00), P&#x2005;=&#x2005;.05). The subgroup analysis showed no statistically significant difference between the age-related macular degeneration group and control group in <2 years of metformin usage and 2 years or more (OR&#x2005;=&#x2005;0.89, CI&#x2005;=&#x2005;(0.52-1.52), P&#x2005;=&#x2005;.67), (OR&#x2005;=&#x2005;0.95, CI&#x2005;=&#x2005;(0.82-1.10), P&#x2005;=&#x2005;.47), respectively.<br><br>CONCLUSION: Our study revealed no role of metformin in decreasing age-related macular degeneration risk in past or present usage. More RCTs are needed to support our findings in evaluating the actual role of metformin in age-related macular degeneration.},
}
@article {pmid38995899,
year = {2024},
author = {Bonilla-Escobar, FJ and Ghobrial, AI and Gallagher, DS and Eller, A and Waxman, EL},
title = {Comprehensive insights into a decade-long journey: The evolution, impact, and human factors of an asynchronous telemedicine program for diabetic retinopathy screening in Pennsylvania, United States.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0305586},
pmid = {38995899},
issn = {1932-6203},
mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; *Telemedicine ; Male ; Female ; Middle Aged ; Pennsylvania ; Aged ; Mass Screening/methods ; COVID-19/epidemiology ; Adult ; },
abstract = {Diabetic Retinopathy stands as a leading cause of irreversible blindness, necessitating frequent examinations, especially in the early stages where effective treatments are available. However, current examination rates vary widely, ranging from 25-60%. This study scrutinizes the Point-of-Care Diabetic Retinopathy Examination Program at the University of Pittsburgh/UPMC, delving into its composition, evolution, challenges, solutions, and improvement opportunities. Employing a narrative approach, insights are gathered from key stakeholders, including ophthalmologists and staff from primary care clinics. A quantitative analysis from 2008 to 2020 provides a comprehensive overview of program outcomes, covering 94 primary care offices with 51 retinal cameras. Program components feature automated non-mydriatic 45° retinal cameras, a dedicated coordinator, rigorous training, and standardized workflows. Over this period, the program conducted 21,960 exams in 16,458 unique individuals, revealing a diverse population with an average age of 58.5 and a balanced gender distribution. Average body mass index (33.96±8.02 kg/m2) and hemoglobin A1c (7.58%±1.88%) surpassed normal ranges, indicating prevalent risk factors for diabetes-related complications. Notably, 24.2% of patients underwent more than one exam, emphasizing program engagement. Findings indicated that 86.3% of exams were gradable, with 59.0% within normal limits, 12.1% showing some evidence of diabetic retinopathy, and 6.4% exhibiting vision-threatening diabetic retinopathy. Follow-up appointments with ophthalmologists were recommended in 31.5% of exams due to indeterminate results, positive diabetic retinopathy (≥moderate or macular exudate), or other findings like age-related macular degeneration or suspected glaucoma. The program demonstrated high reproducibility across diverse healthcare settings, featuring a sustainable model with minimal camera downtime, standardized workflows, and financial support from grants, health systems, and clinical revenues. Despite COVID-19 pandemic challenges, this research emphasizes the program's reproducibility, user-friendly evolution, and promising outcomes. Beyond technical contributions, it highlights human factors influencing program success. Future research could explore adherence to follow-up ophthalmological recommendations and its associated factors.},
}
@article {pmid38995352,
year = {2024},
author = {Yoshida, H and Inoda, S and Takahashi, H and Takahashi, R and Hashimoto, Y and Takahashi, H and Kawashima, H and Yanagi, Y},
title = {Two-year outcomes of intravitreal brolucizumab for neovascular age-related macular degeneration: treat, extend, and stop-protocol.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {12},
pages = {3815-3823},
pmid = {38995352},
issn = {1435-702X},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Fluorescein Angiography ; Follow-Up Studies ; Fundus Oculi ; *Intravitreal Injections ; Prospective Studies ; Time Factors ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; },
abstract = {PURPOSE: To investigate the real-world 2-year treatment outcomes of intravitreal brolucizumab (IVBr) for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This multicenter, prospective, and interventional study included 53 eyes treated with brolucizumab from October 2020 to August 2021 at 3 institutions. A modified treat-and-extend (TAE) regimen with predefined discontinuation criteria was used. The mTAE regimen was discontinued if patients responded positively and achieved a treatment interval of 16 weeks twice with no sign of recurrence. The number of patients discontinuing TAE and the visual and anatomic changes at 1 and 2 years after the first IVBr were evaluated.<br><br>RESULTS: Thirty-eight eyes from 38 patients (71%) completed the 2-year observation period and 7 eyes from 7 patients experienced intraocular inflammation (IOI). Of these 38 patients, 18 (47%) could discontinue the TAE at a median [interquartile range] of 13.1 [12.9-16.8] months after the first IVBr. Best-corrected visual acuity, central subfield retinal thickness, and central choroidal thickness were significantly improved compared with baseline at both 1 and 2 years after the first IVBr (all P&#x2009;<&#x2009;0.001). An extension study revealed a 1-year recurrence rate of 5.6% (standard deviation, 5.4%) after TAE discontinuation.<br><br>CONCLUSIONS: While IOI is a concern with brolucizumab, careful observation allows discontinuing the TAE regimen in patients treated with IVBr. Moreover, brolucizumab may reduce the risk of recurrence after treatment interruption.<br><br>TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (http://www.umin.ac.jp/ ; R000050688 UMIN 000044374).},
}
@article {pmid38995351,
year = {2024},
author = {Hamedani, AG and Chang, AY and Chen, Y and VanderBeek, BL},
title = {Disparities in glaucoma and macular degeneration healthcare utilization among persons living with dementia in the United States.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {12},
pages = {3947-3955},
pmid = {38995351},
issn = {1435-702X},
support = {2P30EYEY001583/EY/NEI NIH HHS/United States ; N/A//Paul MacKall and Evanina Bell MacKall Trust/ ; K23 EY033438/EY/NEI NIH HHS/United States ; N/A//Metzger Family/ ; N/A//Research to Prevent Blindness/ ; K23 EY033438-02/EY/NEI NIH HHS/United States ; K23 EY033438-02/EY/NEI NIH HHS/United States ; 2P30EYEY001583/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Dementia/epidemiology/diagnosis ; *Glaucoma, Open-Angle/diagnosis/epidemiology ; Healthcare Disparities/statistics &amp; numerical data ; Incidence ; Intraocular Pressure/physiology ; Patient Acceptance of Health Care/statistics &amp; numerical data ; Retrospective Studies ; Tomography, Optical Coherence ; United States/epidemiology ; Visual Field Tests ; Visual Fields/physiology ; Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; },
abstract = {PURPOSE: Dementia is common among patients with primary open angle glaucoma (POAG) and neovascular age-related macular degeneration (nAMD). This study compares visit frequency, diagnostic test utilization, and treatment patterns for POAG and nAMD among persons with vs. without dementia.<br><br>METHODS: Optum's de-identified Clinformatics[&#xae;] Data Mart Database (January 1, 2000-June 30, 2022) was used for this study. Two cohorts were created from newly diagnosed POAG or nAMD patients. Within each cohort, an exposure cohort was created of newly diagnosed dementia patients. The primary outcome was the number of visits to an eye care provider. Secondary analyses for the POAG cohort assessed the number of visual field tests, optical coherence tomography (OCT), and glaucoma medication prescription coverage. The secondary analysis for the nAMD cohort included the number of injections performed. Poisson regression was used to determine the relative rates of outcomes.<br><br>RESULTS: POAG patients with dementia had reduced rates of eye care visits (RR 0.76, 95% CI: 0.75-0.77), lower rates of testing utilization for visual fields (RR 0.66, 95% CI: 0.63-0.68) and OCT (RR 0.67, 95% CI: 0.64-0.69), and a lower rate of glaucoma prescription medication coverage (RR 0.83, 95% CI: 0.83-0.83). nAMD patients with dementia had reduced rates of eye care visits (RR 0.74, 95% CI: 0.70-0.79) and received fewer intravitreal injections (RR 0.64, 95% CI: 0.58-0.69) than those without dementia.<br><br>CONCLUSIONS: POAG and nAMD patients with dementia obtained less eye care and less monitoring and treatment of their disease. These findings suggest that this population may be vulnerable to gaps in ophthalmic care.},
}
@article {pmid38994762,
year = {2024},
author = {Li, J and Li, J and Cao, Y and Yuan, J and Shen, Y and Lei, L and Li, K},
title = {Triptonide protects retinal cells from oxidative damage via activation of Nrf2 signaling.},
journal = {International journal of molecular medicine},
volume = {54},
number = {3},
pages = {},
pmid = {38994762},
issn = {1791-244X},
mesh = {*Oxidative Stress/drug effects ; Animals ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/drug effects ; Mice ; *Retina/drug effects/metabolism/pathology ; Triterpenes/pharmacology ; Male ; Apoptosis/drug effects ; Humans ; Mice, Inbred C57BL ; Protective Agents/pharmacology ; Cell Line ; Hydrogen Peroxide ; },
abstract = {Age‑related macular degeneration (AMD) is an ocular disease that threatens the visual function of older adults worldwide. Key pathological processes involved in AMD include oxidative stress, inflammation and choroidal vascular dysfunction. Retinal pigment epithelial cells and Müller cells are most susceptible to oxidative stress. Traditional herbal medicines are increasingly being investigated in the field of personalized medicine in ophthalmology. Triptonide (Tn) is a diterpene tricyclic oxide, the main active ingredient in the extract from the Chinese herbal medicinal plant Tripterygium wilfordii, and is considered an effective immunosuppressant and anti‑inflammatory drug. The present study investigated the potential beneficial role of Tn in retinal oxidative damage in order to achieve personalized treatment for early AMD. An oxidative stress model of retinal cells induced by H2O2 and a retinal injury model of mice induced by light and N‑Methyl‑D‑aspartic acid were constructed. In vitro, JC‑1 staining, flow cytometry and apoptosis assay confirmed that low concentrations of Tn effectively protected retinal cells from oxidative damage, and reverse transcription‑quantitative PCR and western blotting analyses revealed that Tn reduced the expression of retinal oxidative stress‑related genes and inflammatory factors, which may depend on the PI3K/AKT/mTOR‑induced Nrf2 signaling pathway. In vivo, by retinal immunohistochemistry, hematoxylin and eosin staining and electroretinogram assay, it was found that retinal function and structure improved and choroidal neovascularization was significantly inhibited after Tn pretreatment. These results suggested that Tn is an efficient Nrf2 activator, which can be expected to become a new intervention for diseases such as AMD, to inhibit retinal oxidative stress damage and pathological neovascularization.},
}
@article {pmid38994366,
year = {2024},
author = {Yang, Y and Lin, Y and Han, Z and Wang, B and Zheng, W and Wei, L},
title = {Ferroptosis: a novel mechanism of cell death in ophthalmic conditions.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1440309},
pmid = {38994366},
issn = {1664-3224},
mesh = {*Ferroptosis ; Humans ; *Eye Diseases/metabolism/pathology ; Animals ; Reactive Oxygen Species/metabolism ; Lipid Peroxidation ; Signal Transduction ; Cell Death ; Iron/metabolism ; },
abstract = {Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation and differs from programmed cell death, such as apoptosis, necrosis, and autophagy. Ferroptosis is associated with a variety of physiological and pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence and development of diseases by targeting metabolic pathways and signaling pathways in tumors, ischemic organ damage, and other degenerative diseases related to lipid peroxidation. Increasing evidence suggests that ferroptosis is closely linked to the onset and progression of various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, and retinoblastoma. Our review of the current research on ferroptosis in ophthalmic diseases reveals significant advancements in our understanding of the pathogenesis, aetiology, and treatment of these conditions.},
}
@article {pmid38993872,
year = {2023},
author = {Beaver, D and Limnios, IJ},
title = {A treatment within sight: challenges in the development of stem cell-derived photoreceptor therapies for retinal degenerative diseases.},
journal = {Frontiers in transplantation},
volume = {2},
number = {},
pages = {1130086},
pmid = {38993872},
issn = {2813-2440},
abstract = {Stem cell therapies can potentially treat various retinal degenerative diseases, including age-related macular degeneration (AMD) and inherited retinal diseases like retinitis pigmentosa. For these diseases, transplanted cells may include stem cell-derived retinal pigmented epithelial (RPE) cells, photoreceptors, or a combination of both. Although stem cell-derived RPE cells have progressed to human clinical trials, therapies using photoreceptors and other retinal cell types are lagging. In this review, we discuss the potential use of human pluripotent stem cell (hPSC)-derived photoreceptors for the treatment of retinal degeneration and highlight the progress and challenges for their efficient production and clinical application in regenerative medicine.},
}
@article {pmid38990973,
year = {2024},
author = {Moon, SY and Kim, HJ and Kim, JK and Kim, J and Choi, JS and Won, SY and Park, K and Lee, SHS},
title = {An examination of the mechanisms driving the therapeutic effects of an AAV expressing a soluble variant of VEGF receptor-1.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0305466},
pmid = {38990973},
issn = {1932-6203},
mesh = {Humans ; *Vascular Endothelial Growth Factor Receptor-1/genetics/metabolism ; *Dependovirus/genetics ; *Human Umbilical Vein Endothelial Cells ; *Vascular Endothelial Growth Factor A/metabolism/genetics ; *Genetic Therapy/methods ; Genetic Vectors/genetics ; Cell Proliferation ; Macular Degeneration/therapy/genetics/metabolism ; Diabetic Retinopathy/therapy/genetics/metabolism ; Vascular Endothelial Growth Factor B/genetics/metabolism ; Placenta Growth Factor/genetics/metabolism ; },
abstract = {In previous animal model studies, we demonstrated the potential of rAAV2-sVEGFRv-1, which encodes a truncated variant of the alternatively spliced soluble version of VEGF receptor-1 (VEGFR1), as a human gene therapy for age-related macular degeneration (AMD) and diabetic retinopathy (DR). Here, we elucidate in vitro some of the mechanisms by which rAAV2-sVEGFRv-1 exerts its therapeutic effects. Human umbilical vein endothelial cells (HUVECs) were infected with rAAV2-sVEGFRv-1 or a control virus vector in the presence of members of the VEGF family to identify potential binding partners via ELISA, which showed that VEGF-A, VEGF-B, and placental growth factor (PlGF) are all ligands of its transgene product. In order to determine the effects of rAAV2-sVEGFRv-1 on cell proliferation and permeability, processes that are important to the progression AMD and DR, HUVECs were infected with the therapeutic virus vector under the stimulation of VEGF-A, the major driver of the neovascularization that characterizes the forms of these conditions most associated with vision loss. rAAV2-sVEGFRv-1 treatment, as a result, markedly reduced the extent to which these processes occurred, with the latter determined by measuring zonula occludens 1 expression. Finally, the human microglial HMC3 cell line was used to show the effects of the therapeutic virus vector upon inflammatory processes, another major contributor to angiogenic eye disease pathophysiology, with rAAV2-sVEGFRv-1 reducing therein the secretion of pro-inflammatory cytokines interleukin (IL)-1β and IL-6. Combined with our previously published in vivo data, the in vitro activity of the expressed transgene here further demonstrates the great promise of rAAV2-sVEGFRv-1 as a potential human gene therapeutic for addressing angiogenic ocular conditions.},
}
@article {pmid38990568,
year = {2024},
author = {Hallak, JA and Abbasi, A and Goldberg, RA and Modi, Y and Zhao, C and Jing, Y and Chen, N and Mercer, D and Sahu, S and Alobaidi, A and López, FJ and Luhrs, K and Waring, JF and den Hollander, AI and Smaoui, N},
title = {Janus Kinase Inhibitor Therapy and Risk of Age-Related Macular Degeneration in Autoimmune Disease.},
journal = {JAMA ophthalmology},
volume = {142},
number = {8},
pages = {750-758},
pmid = {38990568},
issn = {2168-6173},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Autoimmune Diseases/complications/drug therapy/epidemiology ; Databases, Factual ; Incidence ; *Janus Kinase Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy/epidemiology/etiology ; Retrospective Studies ; Risk Factors ; United States/epidemiology ; },
abstract = {IMPORTANCE: The involvement of chronic inflammation in the pathogenesis of age-related macular degeneration (AMD) opens therapeutic possibilities to AMD management.<br><br>OBJECTIVE: To determine whether Janus kinase inhibitors (JAKis) are associated with a reduced risk of AMD development in patients with autoimmune diseases.<br><br>This retrospective observational cohort study used administrative claims data from Merative MarketScan research databases (Commercial and Medicare Supplemental) and Optum Clinformatics Data Mart databases between January 1, 2010, and January 31, 2022. Patients with autoimmune diseases satisfying study eligibility criteria and who received JAKi treatment (9126 in MarketScan and 5667 in Optum) were propensity score matched (1:1) to identical numbers of study-eligible patients who received non-JAKi-based immunotherapy.<br><br>EXPOSURE: Treatment duration of 6 months or longer.<br><br>MAIN OUTCOMES AND MEASURES: Incidence rates of AMD (exudative and nonexudative) over the first 6 to 18 months of treatment were determined, and bayesian Poisson regression models were used to estimate incidence rate ratios, 95% CIs, and posterior probabilities of AMD.<br><br>RESULTS: After matching, female sex represented the majority of the patient population in both MarketScan and Optum (14&#x202f;019/18&#x202f;252 [76.6%] and 8563/3364 [75.2%], respectively in the JAKi patient population). More than 60% of the patient population was older than 55 years of age in both cohorts. Over the specified treatment period, a 49% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (10/9126 events; adjusted incidence rate ratio [AIRR], 0.51; 95% CI, 0.19-0.90) vs those who received non-JAKi therapy (43/9126 events; AIRR, 1 [reference]) in MarketScan, and a 73% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (3/5667 events; AIRR, 0.27; 95% CI, 0.03-0.74) vs those who received non-JAKi therapy (21/5667 events; AIRR, 1 [reference]) in Optum. The absolute percentage reductions were 0.36% (MarketScan) and 0.32% (Optum), favoring patients who received JAKi therapy. Posterior probabilities of the adjusted risk being less than unity were 97.6% (MarketScan) and 98.9% (Optum) for those who received JAKi therapy vs those who received non-JAKi therapy in MarketScan and Optum, respectively.<br><br>CONCLUSIONS AND RELEVANCE: JAKi use may be associated with a reduced risk of incident AMD in US adults with major autoimmune diseases. The absolute percentage reduction is consistent with a potential role for JAKi in this population. Future studies with long-term follow-up are recommended to investigate the association between JAKi use and incident AMD in other disease indications. Investigation into the role of systemic inflammation and JAK-signal transducers and activators of transcription signaling in AMD may improve understanding of the pathophysiology of AMD and lead to new treatment options.},
}
@article {pmid38988860,
year = {2024},
author = {Lee, Y and Lee, L and Zhang, L and Zhou, Q},
title = {Association between fatty acid intake and age-related macular degeneration: a meta-analysis.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1403987},
pmid = {38988860},
issn = {2296-861X},
abstract = {OBJECTIVE: The association of age-related macular degeneration (AMD) with the intake of high and low fatty acids (FAs), respectively, remains controversial. To this end, we performed a comprehensive meta-analysis of all the existing studies on the association of various intake levels of FA subtypes with AMD to determine these associations.<br><br>METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE databases was conducted from inception to September 2023. To compare the highest and lowest groups, odds ratio (OR) with 95% confidence intervals (CIs) was analyzed with a random-effects model/fixed-effects model.<br><br>RESULTS: A high intake of omega-3 LCPUFAs (OR:0.67; 95%CI:[0.51, 0.88]; p&#x2009;=&#x2009;0.004), DHA (OR:0.80; 95%CI:[0.70, 0.90]; p&#x2009;<&#x2009;0.001), EPA (OR:0.91; 95%CI:[0.86, 0.97]; p&#x2009;=&#x2009;0.004), and simultaneous intake of DHA and EPA (OR:0.79; 95%CI:[0.67, 0.93]; p&#x2009;=&#x2009;0.035) significantly reduced the risk of overall AMD. Conversely, a high intake of trans-FAs (OR: 2.05; 95%CI: [1.29, 3.25]; p&#x2009;=&#x2009;0.002) was significantly related to an increased risk of advanced AMD compared to the low-intake group. The subgroup analysis results are shown in the articles.<br><br>CONCLUSION: Increasing dietary intake of omega-3 LCPUFAs, specifically DHA, and EPA, or the simultaneous intake of DHA and EPA, is significantly associated with a reduced risk of overall AMD. Various subtypes of omega-3 also have a significant association with a reduced risk of different stages of AMD. The high intake of trans-fatty acids (TFAs) is significantly and positively correlated with the risk of advanced AMD. This could further support the idea that consuming foods rich in omega-3 LCPUFAs and reducing consumption of foods rich in TFAs may prevent AMD.<br><br>https://www.crd.york.ac.uk/prospero/, identifier CRD42023467227.},
}
@article {pmid38988586,
year = {2024},
author = {Wang, L and Tian, Y and Li, L and Cai, M and Zhou, X and Su, W and Hua, X and Yuan, X},
title = {Temporary alleviation of MAPK by arbutin alleviates oxidative damage in the retina and ARPE-19 cells.},
journal = {Heliyon},
volume = {10},
number = {12},
pages = {e32887},
pmid = {38988586},
issn = {2405-8440},
abstract = {Dry age-related macular degeneration (AMD) is one of the main diseases that causes blindness in humans, and the number of cases is increasing yearly. However, effective treatments are unavailable, and arbutin (ARB) has been reported to have antioxidant, anti-inflammatory, and anti-aging effects in other age-related diseases. However, whether ARB can be used to treat dry AMD remains unknown. To explore the therapeutic potential and molecular mechanism of arbutin in the treatment of dry AMD. MTT assays, reactive oxygen species (ROS) production assays, flow cytometry assays, qPCR and western blotting were used to assess the impact of ARB on human RPECs induced by H2O2. A transcriptome sequencing assay was used to further explore how ARB acts on human RPECs treated with H2O2. Hematoxylin and eosin (H&amp;E) staining and total antioxidant capacity (T-AOC) assays were used to observe the impact of ARB on mouse retina induced by sodium iodate. ARB counteracted the H2O2-induced reduction in human RPECs viability, ARB reversed H2O2-induced cellular ROS production by increasing the expression of antioxidant-related genes and proteins, ARB also reversed H2O2-induced cell apoptosis by altering the expression of apoptosis-related genes and proteins. Transcriptome sequencing and western blotting showed that ARB reduced ERK1/2 and P-38 phosphorylation to prevent H2O2-induced oxidation damage. The in vivo experiments demonstrated that ARB protected against retinal morphology injury in mice, increased serum T-AOC levels and increased antioxidant oxidase gene expression levels in the mouse retina induced by sodium iodate. We concluded that ARB reversed the H2O2-induced decrease in human RPECs viability through the inhibition of ROS production and apoptosis. The ERK1/2 and P38 MAPK signaling pathways may mediate this process. ARB maintained retinal morphology, increased serum T-AOC level and improved the expression of antioxidant oxidase genes in mice.},
}
@article {pmid39734536,
year = {2024},
author = {Wang, S and Li, W and Chen, M and Cao, Y and Lu, W and Li, X},
title = {The retinal pigment epithelium: Functions and roles in ocular diseases.},
journal = {Fundamental research},
volume = {4},
number = {6},
pages = {1710-1718},
pmid = {39734536},
issn = {2667-3258},
abstract = {The retinal pigment epithelium (RPE) between retinal photoreceptors and choroidal capillaries is a single layer of cells that are of critical importance to the eye. RPE cells are derived from the anterior neural plate of neuroectodermal origin. Instructed by specific molecules and signaling pathways, the RPE undergoes formation and maturation to form a functional unit together with photoreceptors. The RPE plays crucial roles in maintaining normal retinal structure and functions, such as phagocytosis; barrier function; transportation of nutrients, ions, and water; resistance to oxidative damage; maintenance of visual cycle; and production of various important factors. RPE cells have an efficient metabolic machinery to provide sufficient energy to the retina. RPE dysfunction or atrophy can lead to many retinopathies, such as age-related macular degeneration and proliferative vitreoretinopathy. Here, we discuss RPE development, functions, and roles in various ocular diseases, and the mechanisms involved. A better understanding of the functions of the RPE and related regulatory pathways may help identify novel or better therapies for the treatment of many blinding diseases.},
}
@article {pmid39298728,
year = {2023},
author = {Emir, B and Colak, E},
title = {Performance analysis of pretrained convolutional neural network models for ophthalmological disease classification.},
journal = {Arquivos brasileiros de oftalmologia},
volume = {87},
number = {5},
pages = {e20220124},
pmid = {39298728},
issn = {1678-2925},
mesh = {Humans ; *Neural Networks, Computer ; *Eye Diseases/classification/diagnosis ; Sensitivity and Specificity ; Reproducibility of Results ; Databases, Factual ; Fundus Oculi ; Diabetic Retinopathy/classification/diagnosis/diagnostic imaging ; Macular Degeneration/classification/diagnostic imaging ; },
abstract = {PURPOSE: This study aimed to evaluate the classification performance of pretrained convolutional neural network models or architectures using fundus image dataset containing eight disease labels.<br><br>METHODS: A publicly available ocular disease intelligent recognition database has been used for the diagnosis of eight diseases. This ocular disease intelligent recognition database has a total of 10,000 fundus images from both eyes of 5,000 patients for the following eight diseases: healthy, diabetic retinopathy, glaucoma, cataract, age-related macular degeneration, hypertension, myopia, and others. Ocular disease classification performances were investigated by constructing three pretrained convolutional neural network architectures including VGG16, Inceptionv3, and ResNet50 models with adaptive moment optimizer. These models were implemented in Google Colab, which made the task straight-forward without spending hours installing the environment and supporting libraries. To evaluate the effectiveness of the models, the dataset was divided into 70%, 10%, and 20% for training, validation, and testing, respectively. For each classification, the training images were augmented to 10,000 fundus images.<br><br>RESULTS: ResNet50 achieved an accuracy of 97.1%; sensitivity, 78.5%; specificity, 98.5%; and precision, 79.7%, and had the best area under the curve and final score to classify cataract (area under the curve = 0.964, final score = 0.903). By contrast, VGG16 achieved an accuracy of 96.2%; sensitivity, 56.9%; specificity, 99.2%; precision, 84.1%; area under the curve, 0.949; and final score, 0.857.<br><br>CONCLUSIONS: These results demonstrate the ability of the pretrained convolutional neural network architectures to identify ophthalmological diseases from fundus images. ResNet50 can be a good architecture to solve problems in disease detection and classification of glaucoma, cataract, hypertension, and myopia; Inceptionv3 for age-related macular degeneration, and other disease; and VGG16 for normal and diabetic retinopathy.},
}
@article {pmid39491894,
year = {2022},
author = {Campos Polo, R and Gómez Sánchez, I},
title = {OCT angiography biomarkers in type 1 choroidal neovascularisation after one year of aflibercept treatment.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {97},
number = {11},
pages = {639-645},
doi = {10.1016/j.oftale.2021.02.005},
pmid = {39491894},
issn = {2173-5794},
abstract = {OBJECTIVE: To assess the activity of biomarkers, through OCT angiography (OCTA), of choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) treated with aflibercept. As secondary endpoints, visual acuity (VA) and the relationship between biomarkers and visual prognosis were also studied.<br><br>MATERIAL AND METHODS: Prospective study that examined 33 eyes of 40 na&#xef;ve patients with type 1 CNV secondary to AMD, who had been treated with aflibercept, according to summary of product characteristics, for one year. The patients were evaluated at the time of diagnosis, and at 4, 8 and 12 months.<br><br>RESULTS: The mean VA gain at 12 months was 15.2 &#xb1; 3.3 letters. The area of lesion decreased 1.2 &#xb1; 1.0 mm[2] in the 4th month (P&#x202f;<&#x202f;.0001), remaining stable afterwards. The presence of tiny capillaries, anastomosis and perilesional hypointense halo was reduced by 85%, 70% and 25%, respectively, at 12 months of follow-up. The peripheral vascular arcade changed morphology, from having a leafy appearance to having a sharp appearance in 90% of cases. The size of the lesion and the presence/absence of perilesional hypointense halo were independently associated with the final VA, in such a way that larger lesions and the absence of a perilesional hypointense halo at the baseline visit were associated with less VA gain.<br><br>CONCLUSIONS: The OCTA is a useful, non-invasive tool that provides quantitative and qualitative information on the remodelling of the CNV vascular network after antiangiogenic therapy.},
}
@article {pmid38987643,
year = {2025},
author = {Wijesingha, N and Kotecha, A and Margaron, P and Sivaprasad, S},
title = {Infographic: 2-year efficacy, durability and safety of intravitreal faricimab with treat-and-extend dosing up to 16 weeks in neovascular age-related macular degeneration (pooled results from TENAYA and LUCERNE).},
journal = {Eye (London, England)},
volume = {39},
number = {Suppl 1},
pages = {186-187},
doi = {10.1038/s41433-024-03209-8},
pmid = {38987643},
issn = {1476-5454},
}
@article {pmid38984140,
year = {2024},
author = {Rajeswaren, V and Wagner, BD and Patnaik, JL and Mandava, N and Mathias, MT and Manoharan, N and de Carlo Forest, TE and Gnanaraj, R and Lynch, AM and Palestine, AG and , },
title = {Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy.},
journal = {Frontiers in ophthalmology},
volume = {4},
number = {},
pages = {1356957},
pmid = {38984140},
issn = {2674-0826},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; },
abstract = {INTRODUCTION: Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD.<br><br>METHODS: We examined plasma levels of TNF-&#x3b1; and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-&#x3b1; and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers.<br><br>RESULTS: There were 97 GA, 199 iAMD patients and 139 controls. TNF-&#x3b1; was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p<0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p<0.01. There was a significant positive correlation between TNF-&#x3b1; and VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-&#x3b1; and VEGF in any group.<br><br>DISCUSSION: These findings suggest TNF-&#x3b1; and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-&#x3b1; and VEGF may function as systemic biomarkers for disease development.},
}
@article {pmid38983912,
year = {2024},
author = {Li, X and Li, J and Zeng, W and Wang, B and Du, M and Liang, L and Gao, Y},
title = {Mingjing granule inhibits the subretinal fibrovascular membrane of two-stage laser-induced neovascular age-related macular degeneration in rats.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1384418},
pmid = {38983912},
issn = {1663-9812},
abstract = {OBJECTIVE: The study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the underlying mechanism.<br><br>METHODS: The nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial-choroid-sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, &#x3b1;-smooth muscle actin (&#x3b1;-SMA), and transforming growth factor-beta (TGF-&#x3b2;); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR.<br><br>RESULTS: The current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-&#x3b2;, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, &#x3b1;-SMA, TGF-&#x3b2;, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone.<br><br>CONCLUSION: Combining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.},
}
@article {pmid38983085,
year = {2023},
author = {Dan, YS and Cheong, KX and Lim, SY and Wong, QY and Chong, RS and Wong, CW and Hoang, QV},
title = {Quantitative assessment of the choroidal vasculature in myopic macular degeneration with optical coherence tomographic angiography.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1202445},
pmid = {38983085},
issn = {2674-0826},
abstract = {BACKGROUND: To assess and compare choroidal morphometric vascular parameters, using optical coherence tomographic angiography (OCTA), in highly myopic adults with and without myopic macular degeneration (MMD).<br><br>METHODS: This is a clinic-based observational study of 148 eyes with axial length (AL) &#x2265;25mm, enrolled from the high myopia clinic of the Singapore National Eye Centre. MMD was graded from fundus photographs. Swept source OCT (SS-OCT) and OCTA were performed and assessed for choroidal layer thickness (CT) and choroidal vasculature (choroidal vessel density (CVD), choroidal branch area (CBA) and mean choroidal vessel width (MCVW)) in the different choroidal layers (overall choroidal layer (CL), medium-vessel choroidal layer (MVCL), large-vessel choroidal layer (LVCL)).<br><br>RESULTS: CTCL (r=-0.58, p<0.001), CTMVCL (r=-0.22, p=0.04), MCVWCL (r=-0.58, p<0.001), and CVDCL (r=-0.19, p=0.02) were negatively correlated with AL, while CBACL (r=0.61, p<0.001) was positively correlated. Compared to eyes with no MMD, eyes with MMD2 had lower CTCL (120.37&#xb1;47.18&#xb5;m vs 218.33&#xb1;92.70&#xb5;m, p<0.001), CTMVCL (70.57&#xb1;15.28&#xb5;m vs 85.32&#xb1;23.71&#xb5;m, p=0.04), CTLVCL (101.65&#xb1;25.36&#xb5;m vs 154.55&#xb1;68.41&#xb5;m, p=0.001) and greater CVDCL (71.10&#xb1;3.97% vs 66.97&#xb1;3.63%, p<0.001), CVDMVCL (66.96&#xb1;2.35% vs 65.06&#xb1;2.69%, p=0.002), CVDLVCL (68.36&#xb1;2.56% vs 66.58&#xb1;2.88%, p=0.012), MCVWMVCL (6.14&#xb1;0.34&#xb5;m vs 5.90&#xb1;0.35&#xb5;m, p=0.007), and CBACL (12.69&#xb1;1.38% vs 11.34&#xb1;1.18%, p<0.001). After adjusting for age, thicker CTCL (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.97-0.99, p<0.001), CTMVCL (OR 0.97 (0.94-0.99), p=0.002) and CTLVCL (OR 0.97 (0.96-0.98, p<0.001) were significantly associated with lower odds of MMD2, while increased CVDCL (OR 1.37 (1.20-1.55), p<0.001), CVDMVCL (OR 1.39 (1.12-1.73), p=0.003), CVDLVCL (OR 1.31 (1.07-1.60), p=0.009), CBACL (OR 2.19 (1.55-3.08), p<0.001) and MCVWMVCL (OR 6.97 (1.59-30.51), p=0.01) was significantly associated with higher odds of MMD2.<br><br>CONCLUSION: Decrease in choroidal vessel width, density and thickness, and an increase in vascular branching were observed in eyes with long AL. A thinner and denser choroid with greater branching area and vessel width, which may all be signs of hypoxia, were associated with greater odds of MMD2.},
}
@article {pmid38983043,
year = {2023},
author = {Masson, EAY and Serrano, J and Leger-Charnay, E and Acar, N},
title = {Cholesterol and oxysterols in retinal neuron-glia interactions: relevance for glaucoma.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1303649},
pmid = {38983043},
issn = {2674-0826},
abstract = {Cholesterol is an essential component of cellular membranes, crucial for maintaining their structural and functional integrity. It is especially important for nervous tissues, including the retina, which rely on high amounts of plasma membranes for the transmission of the nervous signal. While cholesterol is by far the most abundant sterol, the retina also contains cholesterol precursors and metabolites, especially oxysterols, which are bioactive molecules. Cholesterol lack or excess is deleterious and some oxysterols are known for their effect on neuron survival. Cholesterol homeostasis must therefore be maintained. Retinal glial cells, especially Müller cells, the principal glial cells of the vertebrate retina, provide mechanical, nutritional, and metabolic support for the neighboring neurons. Several pieces of evidence indicate that Müller cells are major actors of cholesterol homeostasis in the retina, as it is known for other glial cells in the brain. This process is based on a close cooperation with neurons, and sterols can be signaling molecules participating in glia-neuron interactions. While some implication of cholesterol in age-related macular degeneration is now recognized, based on epidemiological and laboratory data, evidence for its role in glaucoma is still scarce. The association between cholesterolemia and glaucoma is controversial, but experimental data suggest that sterols could take part in the pathological processes. It has been demonstrated that Müller glial cells are implicated in the development of glaucoma through an ambivalent reactive retinal gliosis process. The early steps contribute to maintaining retinal homeostasis and favor the survival of ganglion cells, which are targeted during glaucoma. If gliosis persists, dysregulation of the neuroprotective functions, cytotoxic effects of gliotic Müller cells and disruption of glia-neuron interactions lead to an acceleration of ganglion cell death. Sterols could play a role in the glial cell response to glaucomatous injury. This represents an understudied but attractive topic to better understand glaucoma and conceive novel preventive or curative strategies. The present review describes the current knowledge on i) sterol metabolism in retinal glial cells, ii) the potential role of cholesterol in glaucoma, and iii) the possible relationships between cholesterol and oxysterols, glial cells and glaucoma. Focus is put on glia-neuron interactions.},
}
@article {pmid38983024,
year = {2023},
author = {Nipp, GE and Lee, T and Sarici, K and Malek, G and Hadziahmetovic, M},
title = {Adult-onset foveomacular vitelliform dystrophy: epidemiology, pathophysiology, imaging, and prognosis.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1237788},
pmid = {38983024},
issn = {2674-0826},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; },
abstract = {Adult-onset foveomacular dystrophy (AOFVD) is a retinal pattern dystrophy that may affect up to 1 in 7,400 individuals. There is much that is unknown regarding this disease's epidemiology, risk factors for development, and rate of progression through its four stages. Advancements in retinal imaging over the past 15 years have enabled improved characterization of the different stages of AOFVD. These imaging advancements also offer new ways of differentiating AOFVD from phenotypically similar retinal diseases like age-related macular degeneration and Best disease. This review synthesizes the most recent discoveries regarding imaging correlates within AOFVD as well as risk factors for the development of AOFVD, complications of AOFVD, and treatment options. Our aim is to provide ophthalmologists a succinct resource so that they may offer clarity, guidance, and appropriate monitoring and treatments for their patients with suspected AOFVD.},
}
@article {pmid38983017,
year = {2023},
author = {Rajanala, K and Dotiwala, F and Upadhyay, A},
title = {Geographic atrophy: pathophysiology and current therapeutic strategies.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1327883},
pmid = {38983017},
issn = {2674-0826},
abstract = {Geographic atrophy (GA) is an advanced stage of age-related macular degeneration (AMD) that leads to gradual and permanent vision loss. GA is characterized by the loss of photoreceptor cells and retinal pigment epithelium (RPE), leading to distinct atrophic patches in the macula, which tends to increase with time. Patients with geographic atrophy often experience a gradual and painless loss of central vision, resulting in difficulty reading, recognizing faces, or performing activities that require detailed vision. The primary risk factor for the development of geographic atrophy is advanced age; however, other risk factors, such as family history, smoking, and certain genetic variations, are also associated with AMD. Diagnosis is usually based on a comprehensive eye examination, including imaging tests such as fundus photography, optical coherence tomography (OCT), and fluorescein angiography. Numerous clinical trials are underway, targeting identified molecular pathways associated with GA that are promising. Recent approvals of Syfovre and Izervay by the FDA for the treatment of GA provide hope to affected patients. Administration of these drugs resulted in slowing the rate of progression of the disease. Though these products provide treatment benefits to the patients, they do not offer a cure for geographic atrophy and are limited in efficacy. Considering these safety concerns and limited treatment benefits, there is still a significant need for therapeutics with improved efficacy, safety profiles, and better patient compliance. This comprehensive review discusses pathophysiology, currently approved products, their limitations, and potential future treatment strategies for GA.},
}
@article {pmid38982998,
year = {2023},
author = {Ibrahim, FNI and Teo, KYC and Tan, TE and Chan, HH and Chandrasekaran, PR and Lee, SY and Tan, ACS and Mathur, R and Chan, CM and Sim, SS and Tan, GSW and Yeo, IYS and Cheung, CMG},
title = {Initial experiences of switching to faricimab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in an Asian population.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1346322},
pmid = {38982998},
issn = {2674-0826},
abstract = {PURPOSE: To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents.<br><br>METHODS: This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED.<br><br>RESULTS: Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (&#xb1; SD)] VA, CST, and MV improved from 0.50 logMAR (&#xb1; 0.27 logMAR) to 0.46 logMAR (&#xb1; 0.27 logMAR) (p = 0.20), 383.35 &#xb5;m (&#xb1; 111.24 &#xb5;m) to 322.46 &#xb5;m (&#xb1; 103.89 &#xb5;m (p < 0.01), and 9.40 mm[3] (&#xb1; 1.52 mm[3]) to 8.75 mm[3] (&#xb1; 1.17 mm[3]) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 &#xb5;m (&#xb1; 151 &#xb5;m) to 149 &#xb5;m (&#xb1; 113 &#xb5;m) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 &#xb5;m (&#xb1; 217.97 &#xb5;m)] and the post switch visit [236.66 &#xb5;m (&#xb1; 189.05 &#xb5;m); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae.<br><br>CONCLUSIONS: In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.},
}
@article {pmid38981710,
year = {2024},
author = {Ameln, J and Saßmannshausen, M and von der Emde, L and Carmichael-Martins, A and Holz, FG and Ach, T and Harmening, WM},
title = {Assessment of local sensitivity in incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) lesions in intermediate age-related macular degeneration (iAMD).},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {38981710},
issn = {2397-3269},
support = {R01 EY027948/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Cross-Sectional Studies ; *Macular Degeneration/pathology/diagnosis/physiopathology ; Female ; Male ; Aged ; *Tomography, Optical Coherence/methods ; *Visual Field Tests/methods ; Visual Acuity/physiology ; Aged, 80 and over ; Visual Fields/physiology ; Ophthalmoscopy/methods ; Atrophy/pathology ; },
abstract = {Lesions of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) are associated with disease progression in age-related macular degeneration. However, the corresponding functional impact of these precursor lesions is unknown.We present a cross-sectional study of four patients employing clinical-grade MAIA (stimulus size: 0.43°, ~125 µm) and adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP) to assess the specific impact of iRORA lesions on retinal sensitivity.AOSLO imaging showed overall reduced photoreceptor reflectivity and patches of hyporeflective regions at drusen with interspersed hyper-reflective foci in iRORA regions. MAIA-MP yielded an average retinal sensitivity loss of -7.3±3.1 dB at iRORA lesions compared with the in-eye control. With AOSLO-MP, the corresponding sensitivity loss was 20.1±4.8 dB.We demonstrated that iRORA lesions are associated with a severe impairment in retinal sensitivity. Larger cohort studies will be necessary to validate our findings.},
}
@article {pmid38980859,
year = {2024},
author = {Więckowska, B and Byszek, K and Rękas, M and Yurochko, T and Shevchenko, M and Skrypnikova, O and Dozsa, C and Toth, M},
title = {How much can we learn from each other? Polish and Hungarian good practices in financing ophthalmology care as a proposal for implementation in Ukraine.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0306562},
pmid = {38980859},
issn = {1932-6203},
mesh = {Humans ; Ukraine ; *Ophthalmology/economics ; Poland ; Hungary ; Delivery of Health Care/economics ; Healthcare Financing ; Corneal Transplantation/economics ; },
abstract = {OBJECTIVES: The article aims to compare payment schemes for cataract, glaucoma, vitrectomy, cornea transplantations, DME, and AMD across Hungary, Poland, and Ukraine, and to identify implementable practices in Ukraine within the context of ongoing healthcare reforms.<br><br>METHODS: Researchers used mixed-method research-with legal documents and data analysis on utilisation of ophthalmology services between 2010 and 2019 and in-depth semi structured interviews with fifteen health experts from Hungary, Poland, and Ukraine. Interviewees, five from each country, were representatives from healthcare providers and payers with at least 10 years' experience in ophthalmology care and knowledge about financing schemes in each country of residence.<br><br>RESULTS: We identified significant differences in healthcare delivery and financing of ophthalmology services between Hungary and Poland, despite both countries rely on Diagnosis-Related Group (DRG) based systems for hospital care. Good practices for financing specific eye treatments like cataract, glaucoma, age-related macular degeneration (AMD), diabetic macular edema (DME), cornea transplantations, and vitrectomy are identified. The financing scheme, including financial products and incentives, can influence the volume of treatments. Access to ophthalmic care is a key concern, with differences in treatment schemes between Hungary (ambulatory care) and Poland (hospital care), leading to higher costs and the need for centralization of complex procedures like cornea transplantations.<br><br>CONCLUSIONS: The article highlights the importance of incentivizing quality improvements and removing financial barriers in Poland, while Hungary should focus on continuous monitoring of treatment methods and flexibility in reimbursement. For Ukraine, the research findings are significant due to ongoing healthcare reform, and the country seeks optimal practices while considering the experiences of other countries.},
}
@article {pmid38980271,
year = {2024},
author = {Tanaka, M and Yasuda, H and Nakamura, S and Shimazawa, M},
title = {H-151, a Selective STING Inhibitor, Has Potential as a Treatment for Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {16},
pmid = {38980271},
issn = {1552-5783},
mesh = {Animals ; Male ; Mice ; Blotting, Western ; Choroid/metabolism/pathology ; *Choroidal Neovascularization/drug therapy/metabolism ; Disease Models, Animal ; Fluorescein Angiography ; Intravitreal Injections ; Macular Degeneration/drug therapy/metabolism ; *Membrane Proteins/metabolism/antagonists &amp; inhibitors ; Mice, Inbred C57BL ; *Nucleotidyltransferases/metabolism/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) stimulator of interferon gene (STING) pathway is a crucial cascade in the inflammatory response initiated by the recognition of cytosolic double-stranded DNA (dsDNA). The aim of this study was to evaluate the effect of STING inhibitor in murine choroidal neovascularization (CNV).<br><br>METHODS: To investigate whether the cGAS-STING pathway is activated during CNV, CNV was induced using laser photocoagulation in male C57BL/6J mice. The expression of change of cGAS and STING during CNV development was confirmed by Western-blotting. H-151, a potent STING palmitoylation antagonist, was used as a STING inhibitor. H-151 was administered intravitreally immediately after laser induction. To confirm the role of the cGAS-STING pathway in CNV formation, we evaluated CNV size and performed fundus fluorescein angiography.<br><br>RESULTS: The expression levels of cGAS and STING were significantly upregulated in the RPE-choroid complex after CNV induction, and dsDNA merged with cGAS was observed in CNV lesions. Intravitreal administration of H-151 suppressed CNV development and fluorescent leakage from neovessels. In CNV lesions, the high expression of STING and cGAS was observed in infiltrating F4/80+ macrophages. H-151 administration attenuated downstream signals of the cGAS-STING pathway, including the phosphorylation of nuclear factor-&#x3ba;B, and downregulated the expression of interleukin 1&#x3b2;.<br><br>CONCLUSIONS: These findings support that the inhibition of cGAS-STING pathway treats abnormal ocular angiogenesis.},
}
@article {pmid38980270,
year = {2024},
author = {Guymer, RH and Silva, R and Ghadessi, M and Leal, S and Gashaw, I and Damask, A and Paulding, C and Rittenhouse, KD},
title = {ANO2 Genetic Variants and Anti-VEGF Treatment Response in Neovascular AMD: A Pharmacogenetic Substudy of VIEW 1 and VIEW 2.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {17},
pmid = {38980270},
issn = {1552-5783},
mesh = {Humans ; Male ; *Intravitreal Injections ; Female ; *Angiogenesis Inhibitors/therapeutic use ; Aged ; *Visual Acuity/physiology ; *Vascular Endothelial Growth Factor A/genetics/antagonists &amp; inhibitors ; *Ranibizumab/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use ; *Genome-Wide Association Study ; *Polymorphism, Single Nucleotide ; *Receptors, Vascular Endothelial Growth Factor/genetics ; *Anoctamins/genetics ; Wet Macular Degeneration/genetics/drug therapy ; Aged, 80 and over ; Genotype ; Treatment Outcome ; Pharmacogenetics ; Pharmacogenomic Testing ; },
abstract = {PURPOSE: This analysis investigated potential associations between gene variants and clinical end points in the VIEW 1 and 2 randomized clinical trials of intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration (AMD).<br><br>METHODS: A genome-wide association analysis was conducted in a subgroup of patients from VIEW 1 and 2 consenting to the optional pharmacogenetic analysis.<br><br>RESULTS: Data were pooled from 780 samples from patients representative of the overall VIEW 1 and 2 populations. After Bonferroni correction for multiplicity and statistical adjustment for baseline risk factors, no significant associations were found between previously identified prognostic AMD gene variants and treatment response according to key prespecified VIEW 1 and 2 end points. Genome-wide, there were no significant genetic associations in patients experiencing gains of &#x2265;15 Early Treatment of Diabetic Retinopathy Study letters after 1 or 2&#xa0;years of treatment. A cluster of variants in ANO2 (encoding anoctamin 2, a calcium-activated chloride channel expressed on photoreceptor cells) on chromosome 12 reached the level of significance for loss of &#x2265;5 letters after 1&#xa0;year of treatment (P < 5 &#xd7; 10-8), with the ANO2 rs2110166 SNP demonstrating highly significant association (P = 1.99 &#xd7; 10-8). Carriers of the ANO2 rs2110166 TT genotype showed a robust increase in visual acuity versus baseline compared with a small decrease in those with the TC genotype.<br><br>CONCLUSIONS: None of the potential prognostic candidate genes were associated with the clinical end points for treated patients. Preliminary analyses suggest an association of ANO2 with retinal function, with a potential impact on vision of approximately one line over at least the first year. Further investigation of the function of ANO2 in retinal pathophysiology is merited.},
}
@article {pmid38979414,
year = {2024},
author = {Qi, S and Zhang, Y and Kong, L and Bi, D and Kong, H and Zhang, S and Zhao, C},
title = {SPI1-mediated macrophage polarization aggravates age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1421012},
pmid = {38979414},
issn = {1664-3224},
mesh = {Animals ; *Macular Degeneration/immunology/metabolism/genetics/pathology ; Mice ; *Macrophages/immunology/metabolism ; *Choroidal Neovascularization/immunology/genetics/metabolism ; *Trans-Activators/genetics/metabolism ; *Disease Models, Animal ; Proto-Oncogene Proteins/genetics/metabolism ; Mice, Inbred C57BL ; Macrophage Activation/genetics ; Humans ; Gene Expression Profiling ; Male ; },
abstract = {OBJECTIVE: This study revealed a core regulator and common upstream mechanisms for the multifaceted pathological processes of age-related macular degeneration (AMD) and provided proof-of-concept for this new therapeutic target.<br><br>METHODS: Comprehensive gene expression analysis was performed using RNA sequencing of eye cup from old mice as well as laser-induced choroidal neovascularization (CNV) mouse model. Through integrative analysis and protein-protein interaction (PPI) analysis, common pathways and key transcription factor was identified simultaneously engaged in age-related retinal degeneration and CNV, the two typical pathological process of AMD. Subsequently, the expression changes of Spi1, the key regulator, as well as the alternation of the downstream mechanisms were validated in both models through qRT-PCR, Elisa, flow cytometry and immunofluorescence. Further, we assessed the impact of Spi1 knockdown in vitro and in vivo using gene intervention vectors carried by adeno-associated virus or lentivirus to test its potential as a therapeutic target.<br><br>RESULTS: Compared to corresponding controls, we found 1,939 and 1,319 genes differentially expressed in eye cups of old and CNV mice respectively. The integrative analysis identified a total of 275 overlapping DEGs, of which 150 genes were co-upregulated. PPI analysis verified a central transcription factor, SPI1. The significant upregulation of Spi1 expression was then validated in both models, accompanied by macrophage polarization towards the M1 phenotype. Finally, SPI1 suppression significantly inhibited M1 polarization of BMDMs and attenuated neovascularization in CNV mice.<br><br>CONCLUSION: This study demonstrates that SPI1 exerts a pivotal role in AMD by regulation of macrophage polarization and innate immune response, offering promise as an innovative target for treating AMD.},
}
@article {pmid38977082,
year = {2024},
author = {Cvekl, A and Vijg, J},
title = {Aging of the eye: Lessons from cataracts and age-related macular degeneration.},
journal = {Ageing research reviews},
volume = {99},
number = {},
pages = {102407},
pmid = {38977082},
issn = {1872-9649},
support = {R01 EY012200/EY/NEI NIH HHS/United States ; P01 AG047200/AG/NIA NIH HHS/United States ; U19 AG056278/AG/NIA NIH HHS/United States ; R01 EY014237/EY/NEI NIH HHS/United States ; P30 AG038072/AG/NIA NIH HHS/United States ; P01 AG017242/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/pathology/physiopathology ; *Aging/physiology/pathology ; *Cataract/physiopathology/pathology ; Animals ; Eye ; },
abstract = {Aging is the greatest risk factor for chronic human diseases, including many eye diseases. Geroscience aims to understand the effects of the aging process on these diseases, including the genetic, molecular, and cellular mechanisms that underlie the increased risk of disease over the lifetime. Understanding of the aging eye increases general knowledge of the cellular physiology impacted by aging processes at various biological extremes. Two major diseases, age-related cataract and age-related macular degeneration (AMD) are caused by dysfunction of the lens and retina, respectively. Lens transparency and light refraction are mediated by lens fiber cells lacking nuclei and other organelles, which provides a unique opportunity to study a single aging hallmark, i.e., loss of proteostasis, within an environment of limited metabolism. In AMD, local dysfunction of the photoreceptors/retinal pigmented epithelium/Bruch's membrane/choriocapillaris complex in the macula leads to the loss of photoreceptors and eventually loss of central vision, and is driven by nearly all the hallmarks of aging and shares features with Alzheimer's disease, Parkinson's disease, cardiovascular disease, and diabetes. The aging eye can function as a model for studying basic mechanisms of aging and, vice versa, well-defined hallmarks of aging can be used as tools to understand age-related eye disease.},
}
@article {pmid38976148,
year = {2024},
author = {Debourdeau, E and Beylerian, H and Nguyen, V and Barthelmes, D and Gillies, M and Gabrielle, PH and Vujosevic, S and Otoole, L and Puzo, M and Creuzot-Garcher, C and Wolff, B and Daien, V and , },
title = {Treat-and-Extend Versus Pro re nata Regimens of Ranibizumab and Aflibercept in Neovascular Age-Related Macular Degeneration: A Comparative Study from Routine Clinical Practice.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {9},
pages = {2343-2355},
pmid = {38976148},
issn = {2193-8245},
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or "treat-and-extend" (T&amp;E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&amp;E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&amp;E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&amp;E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice.<br><br>METHODS: We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-na&#xef;ve eyes starting nAMD treatment with at least three injections using a T&amp;E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2&#xa0;years versus baseline. The secondary outcome was the number of injections at 2&#xa0;years.<br><br>RESULTS: From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&amp;E regimen. At 24&#xa0;months, patients on the T&amp;E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+&#x2009;4.2 [3.1, 5.2] vs.&#x2009;+&#x2009;1.3 [0.1, 2.6] letters; p&#x2009;<&#x2009;0.001), with more injections (14.9 standard deviation(SD) 4.3) vs. 9.8(SD 4.3); p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Eyes treated with a T&amp;E regimen had better VA outcomes from VEGF inhibitors than eyes treated PRN. This large real-world data assessment supports previous data from randomized clinical trials that the T&amp;E regimen delivers better outcomes than PRN.},
}
@article {pmid38976126,
year = {2024},
author = {Lee, Y and Zalewski, D and Oleksy, P and Wylęgała, E and Orski, M and Lee, J and Kim, S},
title = {Usability of the SB11 Pre-filled Syringe (PFS) in Patients with Retinal Diseases.},
journal = {Advances in therapy},
volume = {41},
number = {8},
pages = {3426-3436},
pmid = {38976126},
issn = {1865-8652},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use/adverse effects ; Biosimilar Pharmaceuticals/therapeutic use/administration &amp; dosage ; *Intravitreal Injections ; Macular Degeneration/drug therapy/complications ; *Macular Edema/drug therapy/etiology ; *Ranibizumab/administration &amp; dosage/therapeutic use ; Retinal Diseases/drug therapy ; *Retinal Vein Occlusion/drug therapy/complications ; *Syringes ; },
abstract = {INTRODUCTION: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis[®]; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO).<br><br>METHODS: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5&#xa0;mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7&#xa0;days after injection of the investigational product.<br><br>RESULTS: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study.<br><br>CONCLUSIONS: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12.},
}
@article {pmid38975944,
year = {2024},
author = {Murari, J and Gautier, J and Daout, J and Krafft, L and Senée, P and Mecê, P and Grieve, K and Seiple, W and Sheynikhovich, D and Meimon, S and Paques, M and Arleo, A},
title = {Foveolar Drusen Decrease Fixation Stability in Pre-Symptomatic AMD.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {13},
pmid = {38975944},
issn = {1552-5783},
mesh = {Humans ; Female ; *Retinal Drusen/physiopathology/diagnosis ; Male ; *Fixation, Ocular/physiology ; *Fovea Centralis/diagnostic imaging/physiopathology/pathology ; Aged ; Middle Aged ; *Macular Degeneration/physiopathology/diagnosis ; Adult ; Tomography, Optical Coherence/methods ; Ophthalmoscopy/methods ; Visual Acuity/physiology ; Saccades/physiology ; Prodromal Symptoms ; },
abstract = {PURPOSE: This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD).<br><br>METHODS: We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO.<br><br>RESULTS: FEM were measured with high precision (RMS-S2S = 0.0015&#xa0;degrees on human eyes) and small foveal drusen (median diameter = 60 &#xb5;m) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea.<br><br>CONCLUSIONS: A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.},
}
@article {pmid38975538,
year = {2024},
author = {Swaminathan, U and Daigavane, S},
title = {Unveiling the Potential: A Comprehensive Review of Artificial Intelligence Applications in Ophthalmology and Future Prospects.},
journal = {Cureus},
volume = {16},
number = {6},
pages = {e61826},
pmid = {38975538},
issn = {2168-8184},
abstract = {Artificial intelligence (AI) has emerged as a transformative force in healthcare, particularly in the field of ophthalmology. This comprehensive review examines the current applications of AI in ophthalmology, highlighting its significant contributions to diagnostic accuracy, treatment efficacy, and patient care. AI technologies, such as deep learning algorithms, have demonstrated exceptional performance in the early detection and diagnosis of various eye conditions, including diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. Additionally, AI has enhanced the analysis of ophthalmic imaging techniques like optical coherence tomography (OCT) and fundus photography, facilitating more precise disease monitoring and management. The review also explores AI's role in surgical assistance, predictive analytics, and personalized treatment plans, showcasing its potential to revolutionize clinical practice and improve patient outcomes. Despite these advancements, challenges such as data privacy, regulatory hurdles, and ethical considerations remain. The review underscores the need for continued research and collaboration among clinicians, researchers, technology developers, and policymakers to address these challenges and fully harness the potential of AI in improving eye health worldwide. By integrating AI with teleophthalmology and developing AI-driven wearable devices, the future of ophthalmic care promises enhanced accessibility, efficiency, and efficacy, ultimately reducing the global burden of visual impairment and blindness.},
}
@article {pmid38974349,
year = {2024},
author = {Liu, Y and Lawler, T and Liu, Z and Thuruthumaly, C and Vajaranant, T and Wallace, R and Tinker, L and Nalbandyan, M and Mares, J},
title = {Low Macular Pigment Optical Density Is Associated with Manifest Primary Open-Angle Glaucoma in Older Women.},
journal = {Current developments in nutrition},
volume = {8},
number = {6},
pages = {103789},
pmid = {38974349},
issn = {2475-2991},
support = {R01 EY025292/EY/NEI NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND: Lower density of carotenoids lutein and zeaxanthin (L/Z) in the macula (i.e., macular pigment) has been linked to greater risk for age-related eye disease.<br><br>OBJECTIVES: We evaluated whether macular pigment optical density (MPOD) was associated with manifest primary open-angle glaucoma (POAG) among older women in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2).<br><br>METHODS: MPOD was measured with customized heterochromatic flicker photometry in women who attended CAREDS2 (2016-2019) and CAREDS1 (2001-2004) study visits. Manifest POAG at CAREDS2 was assessed using visual fields, disc photos, optical coherence tomography, and medical records. Age-adjusted linear and logistic regression models were used to investigate the cross-sectional association between POAG and MPOD at CAREDS2, and MPOD measured 15 years earlier at CAREDS1.<br><br>RESULTS: Among 426 CAREDS2 participants (mean age: 80 y; range: 69-98 y), 26 eyes with manifest POAG from 26 participants were identified. Glaucomatous eyes had 25% lower MPOD compared to nonglaucomatous eyes [mean (SE): 0.40 (0.05) compared with 0.53 (0.01)] optical density units (ODU), respectively (P = 0.01). Compared with MPOD quartile 1, odds for POAG were lower for women in quartiles 2-4 (P-trend = 0.01). After excluding eyes with age-related macular degeneration, associations were similar but not statistically significant (P-trend = 0.16). Results were similar for MPOD measured at CAREDS1.<br><br>CONCLUSIONS: Our results add to growing evidence that low MPOD may be a novel glaucoma risk factor and support further studies to assess the utility of dietary interventions for glaucoma prevention.},
}
@article {pmid38971923,
year = {2024},
author = {Chandra, S and Raimondi, R and Lim, A and Mohan, A and Melmane, S and Menon, G and Chandran, M and Sivaprasad, S and Burton, BJL and Kotagiri, A},
title = {The effect of four loading intravitreal aflibercept injections on macular fluid in treatment-naïve neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {15},
pages = {3005-3010},
pmid = {38971923},
issn = {1476-5454},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Intravitreal Injections ; *Recombinant Fusion Proteins/administration &amp; dosage ; Male ; Retrospective Studies ; Female ; *Visual Acuity/physiology ; *Tomography, Optical Coherence ; Aged ; *Subretinal Fluid ; *Wet Macular Degeneration/drug therapy/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Macula Lutea/pathology/diagnostic imaging ; Middle Aged ; Fluorescein Angiography ; },
abstract = {PURPOSE: To evaluate the effect of four versus three loading aflibercept injections on macular fluid resolution and visual acuity (VA) in exudative neovascular AMD (nAMD).<br><br>METHODS: Multicentre, retrospective cohort study of treatment na&#xef;ve nAMD eyes undergoing 3 versus 4 loading doses of aflibercept. Change in VA and fluid resolution on optical coherence tomography (OCT), were evaluated at 8 weeks post loading. The primary outcome was proportion of patients with no intraretinal (IRF) and/or subretinal (SRF) fluid at central 1&#x2009;mm and whole macula at 8 weeks after loading. Data were summarised with mean&#x2009;&#xb1;&#x2009;SD for continuous variables, and n (%) for categorical variables.<br><br>RESULTS: Data from 995 patients was analysed (355 patients - 4 loading doses and 640-3 loading doses). At 8 weeks post 4 loading doses proportion of eyes with neither IRF nor SRF, no IRF and no SRF were 62.8%, 88.7% and 79.2% at fovea versus 56.1%, 87.9% and 69.9% in the whole macula, respectively. Fluid resolution at both fovea and macula were significantly higher in eyes with 4 loading injections versus 3 (p&#x2009;=&#x2009;0.0001). The mean VA change was +4.0 (&#xb1;11.3) and +5.4(&#xb1;13.3) letters for 3 and 4 loading doses groups (p&#x2009;=&#x2009;0.09).<br><br>CONCLUSION: Four loading dose injections of aflibercept results in higher proportion of eyes with total fluid resolution in the central subfield and total macular scan when compared to those receiving 3 loading dose injections at 8 weeks post loading phase. However, the better drying effect of 4th loading dose does not translate into better short-term VA outcomes.},
}
@article {pmid38971323,
year = {2024},
author = {Jonas, JB and Bikbov, MM and Kazakbaeva, GM and Wang, YX and Xu, J and Nangia, V and Nangia, PV and Panda-Jonas, S},
title = {Positive and Negative Associations of Myopia with Ocular Diseases in Population-Based Studies.},
journal = {Ophthalmology},
volume = {131},
number = {12},
pages = {1427-1435},
doi = {10.1016/j.ophtha.2024.07.003},
pmid = {38971323},
issn = {1549-4713},
mesh = {Humans ; Middle Aged ; Male ; Female ; Prevalence ; *Myopia/epidemiology/physiopathology ; Aged ; *Macular Degeneration/epidemiology ; Adult ; *Axial Length, Eye/pathology ; China/epidemiology ; *Glaucoma, Open-Angle/epidemiology/physiopathology/diagnosis ; Diabetic Retinopathy/epidemiology/diagnosis ; Glaucoma, Angle-Closure/epidemiology/physiopathology ; India/epidemiology ; Russia/epidemiology ; Rural Population/statistics &amp; numerical data ; Urban Population/statistics &amp; numerical data ; Aged, 80 and over ; Odds Ratio ; Risk Factors ; },
abstract = {PURPOSE: Prevalence of myopia and vision impairment due to myopic macular degeneration and myopia-related optic neuropathies have markedly increased worldwide. We evaluated whether myopia is associated with other ocular disorders.<br><br>DESIGN: Population-based studies conducted in Russia, China, and India.<br><br>PARTICIPANTS: The Russian Ural Eye and Medical Study (UEMS) and the Beijing Eye Study (BES) included 5899 individuals and 4439 individuals (all aged 40+ years), respectively, and the Central India Eye and Medical Study (CIEMS) consisted of 4711 individuals aged 30+ years. The studies were conducted in rural and urban regions in Bashkortostan/Russia, Nagpur/India, and Beijing/China.<br><br>METHODS: The participants underwent a series of ophthalmological and general medical examinations.<br><br>MAIN OUTCOME MEASURES: Axial length as a surrogate for myopia and prevalence of diabetic retinopathy (DR), age-related macular degeneration (AMD), angle-closure glaucoma (ACG), and open-angle glaucoma (OAG).<br><br>RESULTS: In the UEMS, DR prevalence (odds ratio [OR], 0.73), AMD prevalence (OR, 0.85), and ACG prevalence (OR, 0.72) decreased, and OAG prevalence (OR, 1.65) increased with longer axial length in multivariable analyses. In the CIEMS, lower AMD prevalence (OR, 0.81) and lower ACG prevalence (OR, 0.55), and higher OAG prevalence (OR, 1.45) were associated with longer axial length. Diabetic retinopathy prevalence (0.33%) was too low for statistical analysis in the CIEMS. In the BES, prevalence (OR, 0.64) and 10-year incidence of DR (OR, 0.48) and prevalence (OR, 0.83) and 5-year incidence of AMD (OR, 0.996) decreased, and prevalence (OR, 1.35) and 10-year incidence of OAG (OR, 1.40) increased with longer axial length. In all 3 studies, the association between higher OAG prevalence and longer axial length was nonlinear with a slight increase for the moderate myopia range and a steep increase in the highly myopic range.<br><br>CONCLUSIONS: Myopia is associated with a lower prevalence of DR, AMD, and ACG and a lower incidence of DR and AMD, whereas high myopia more than moderate myopia is associated with a higher prevalence and incidence of OAG. Future studies may assess whether in myopia (in particular, in moderate myopia), the myopia-related advantages, that is, lower prevalence of DR, AMD, and ACG, may outweigh the increased risks for OAG and other myopia-related disorders.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid38970762,
year = {2024},
author = {Gandhi, S and Pattathil, N and Choudhry, N},
title = {OCTA: Essential or Gimmick?.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {9},
pages = {2293-2302},
pmid = {38970762},
issn = {2193-8245},
abstract = {This commentary article delves into the transformative role of optical coherence tomography angiography (OCTA) in diagnosing and managing a wide array of eye conditions, including diabetic retinopathy, age-related macular degeneration, retinal vein occlusions, and white dot syndromes. Developed in 2005, OCTA has emerged as a non-invasive, high-resolution imaging technique that offers advantages over traditional fluorescein angiography (FA), providing quicker and safer monitoring of ocular conditions with similar diagnostic accuracy. In diabetic retinopathy, OCTA has been instrumental in early identification of retinal changes, offering quantifiable metrics including perfused capillary density (PCD) for assessing vascular alterations. For age-related macular degeneration (AMD), OCTA has deepened our understanding of non-exudative neovascular AMD, allowing for more effective monitoring and potential earlier initiation of treatment. In cases of retinal vein occlusions, OCTA can reveal specific microvascular features and allow for depth-resolved measurements of the foveal avascular zone, providing significant prognostic implications. OCTA has also been invaluable in studying rare white dot syndromes, enabling nuanced differentiation between conditions that often present similarly. Emerging research also suggests that OCTA can have potential utility in neurodegenerative diseases like Alzheimer's, where retinal vascular patterns could offer diagnostic insights. While OCTA is revolutionizing ophthalmic care, further clinical trials and standardization are needed for its broader adoption into clinical practice.},
}
@article {pmid38967942,
year = {2024},
author = {Tarallo, V and Magliacane Trotta, S and Panico, S and D'Orsi, L and Mercadante, G and Cicatiello, V and De Falco, S},
title = {PlGF and VEGF-A/PlGF Heterodimer are Crucial for Recruitment and Activation of Immune Cells During Choroid Neovascularization.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {8},
pages = {12},
pmid = {38967942},
issn = {1552-5783},
mesh = {Animals ; Mice ; *Choroidal Neovascularization/metabolism ; Disease Models, Animal ; Macrophages/metabolism/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; *Microglia/metabolism ; *Placenta Growth Factor/metabolism ; *Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; },
abstract = {PURPOSE: Recruitment and activation of inflammatory cells, such as retinal microglia/macrophages, in the subretinal space contribute significantly to the pathogenesis of age-related macular degeneration (AMD). This study aims to explore the functional role of vascular endothelial growth factor (VEGF-A), placental growth factor (PlGF) and VEGF-A/PlGF heterodimer in immune homeostasis and activation during pathological laser-induced choroidal neovascularization (CNV).<br><br>METHODS: To investigate these roles, we utilized the PlGF-DE knockin (KI) mouse model, which is the full functional knockout (KO) of PlGF. In this model, mice express a variant of PlGF, named PlGF-DE, that is unable to bind and activate VEGFR-1 but can still form heterodimer with VEGF-A.<br><br>RESULTS: Our findings demonstrate that, although there is no difference in healthy conditions, PlGF-DE-KI mice exhibit decreased microglia reactivity and reduced recruitment of both microglia and monocyte-macrophages, compared to wild-type mice during laser-induced CNV. This impairment is associated with a reduction in VEGF receptor 1 (VEGFR-1) phosphorylation in the retinae of PlGF-DE-KI mice compared to C57Bl6/J mice. Corroborating these data, intravitreal delivery of PlGF or VEGF-A/PlGF heterodimer in PlGF-DE-KI mice rescued the immune cell response at the early phase of CNV compared to VEGF-A delivery.<br><br>CONCLUSIONS: In summary, our study suggests that targeting PlGF and the VEGF-A/PlGF heterodimer, thereby preventing VEGFR-1 activation, could represent a potential therapeutic approach for the management of inflammatory processes in diseases such as AMD.},
}
@article {pmid38966602,
year = {2024},
author = {Moyo, MTG and Adali, T and Tulay, P},
title = {Exploring gellan gum-based hydrogels for regenerating human embryonic stem cells in age-related macular degeneration therapy: A literature review.},
journal = {Regenerative therapy},
volume = {26},
number = {},
pages = {235-250},
pmid = {38966602},
issn = {2352-3204},
abstract = {Age-related macular degeneration (AMD) is a progressive ocular disease marked by the deterioration of retinal photoreceptor cells, leading to central vision decline, predominantly affecting the elderly population worldwide. Current treatment modalities, such as anti-VEGF agents, laser therapy, and photodynamic therapy, aim to manage the condition, with emerging strategies like stem cell replacement therapy showing promise. However, challenges like immune rejection and cell survival hinder the efficacy of stem cell interventions. Regenerative medicine faces obstacles in maximizing stem cell potential due to limitations in mimicking the dynamic cues of the extracellular matrix (ECM) crucial for guiding stem cell behaviour. Innovative biomaterials like gellan gum hydrogels offer tailored microenvironments conducive to enhancing stem cell culture efficacy and tissue regeneration. Gellan gum-based hydrogels, renowned for biocompatibility and customizable mechanical properties, provide crucial support for cell viability, differentiation, and controlled release of therapeutic factors, making them an ideal platform for culturing human embryonic stem cells (hESCs). These hydrogels mimic native tissue mechanics, promoting optimal hESC differentiation while minimizing immune responses and facilitating localized delivery. This review explores the potential of Gellan Gum-Based Hydrogels in regenerative AMD therapy, emphasizing their role in enhancing hESC regeneration and addressing current status, treatment limitations, and future directions.},
}
@article {pmid38965321,
year = {2024},
author = {, and , },
title = {Global estimates on the number of people blind or visually impaired by age-related macular degeneration: a meta-analysis from 2000 to 2020.},
journal = {Eye (London, England)},
volume = {38},
number = {11},
pages = {2070-2082},
pmid = {38965321},
issn = {1476-5454},
mesh = {Aged ; Humans ; *Blindness/epidemiology/etiology ; *Global Health/statistics &amp; numerical data ; *Macular Degeneration/complications ; *Persons with Visual Disabilities/statistics &amp; numerical data ; Prevalence ; *Vision, Low/epidemiology/etiology ; Visual Acuity ; Middle Aged ; Aged, 80 and over ; },
abstract = {BACKGROUND: We aimed to update estimates of global vision loss due to age-related macular degeneration (AMD).<br><br>METHODS: We did a systematic review and meta-analysis of population-based surveys of eye diseases from January, 1980, to October, 2018. We fitted hierarchical models to estimate the prevalence of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (&#x2009;<&#x2009;3/60) caused by AMD, stratified by age, region, and year.<br><br>RESULTS: In 2020, 1.85 million (95%UI: 1.35 to 2.43 million) people were estimated to be blind due to AMD, and another 6.23 million (95%UI: 5.04 to 7.58) with MSVI globally. High-income countries had the highest number of individuals with AMD-related blindness (0.60 million people; 0.46 to 0.77). The crude prevalence of AMD-related blindness in 2020 (among those aged &#x2265; 50 years) was 0.10% (0.07 to 0.12) globally, and the region with the highest prevalence of AMD-related blindness was North Africa/Middle East (0.22%; 0.16 to 0.30). Age-standardized prevalence (using the GBD 2019 data) of AMD-related MSVI in people aged &#x2265; 50 years in 2020 was 0.34% (0.27 to 0.41) globally, and the region with the highest prevalence of AMD-related MSVI was also North Africa/Middle East (0.55%; 0.44 to 0.68). From 2000 to 2020, the estimated crude prevalence of AMD-related blindness decreased globally by 19.29%, while the prevalence of MSVI increased by 10.08%.<br><br>CONCLUSIONS: The estimated increase in the number of individuals with AMD-related blindness and MSVI globally urges the creation of novel treatment modalities and the expansion of rehabilitation services.},
}
@article {pmid38965319,
year = {2024},
author = {Goodchild, C and Bailey, C and Soto Hernaez, J and Ahmed, E and Salvatore, S},
title = {Real world efficacy and durability of faricimab in patients with neovascular AMD (nAMD) who had sub-optimal response to prior anti-VEGF therapy.},
journal = {Eye (London, England)},
volume = {38},
number = {16},
pages = {3059-3064},
pmid = {38965319},
issn = {1476-5454},
mesh = {Humans ; Male ; *Visual Acuity/physiology ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Retrospective Studies ; Aged ; *Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged, 80 and over ; Tomography, Optical Coherence ; Middle Aged ; Treatment Outcome ; Ranibizumab/administration &amp; dosage/therapeutic use ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) remains a primary cause of blindness, with neovascular AMD (nAMD) presenting particular treatment challenges. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies, many patients exhibit a suboptimal response to the previously available anti-vascular endothelial growth factor (anti-VEGF) therapies. This study evaluates the efficacy and treatment interval extension of faricimab in this patient cohort.<br><br>METHODS: In a retrospective single-centre study at University Hospitals of Bristol and Weston, UK, nAMD patients suboptimally responsive to previous anti-VEGF therapies were switched to faricimab. Treatment started with an initiation phase of 4 monthly injections followed by a 'Treat and Extend' protocol. Outcomes included best-recorded visual acuity (BRVA), central subfield thickness (CST), the presence of retinal fluid, and treatment intervals.<br><br>RESULTS: Among 98 eyes of 79 patients, following faricimab treatment, significant reductions in CST and retinal fluid were noted, indicating decreased disease activity. While BRVA changes were not statistically significant, the anatomical improvements suggest a potential therapeutic benefit. Notably, 40% of patients achieved extended treatment intervals, reducing the treatment burden.<br><br>CONCLUSION: Faricimab offers a promising alternative for nAMD patients with suboptimal responses to prior anti-VEGF treatments, demonstrating significant anatomical improvements and the possibility of extended dosing intervals. These findings highlight the need for prospective real-world studies to further assess faricimab's role in nAMD management and its long-term impact on patient outcomes.},
}
@article {pmid38965086,
year = {2024},
author = {Yang, X and Qi, X and Zuo, K and Huang, Y and Bian, X and Wang, J and Yu, H and Feng, Q and Lei, X and Chen, T},
title = {Vitamin D alleviation of oxidative stress in human retinal pigment epithelial cells.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {314},
pmid = {38965086},
issn = {1573-2630},
support = {20204Y0199, 20224044//the Clinical Special Program of Shanghai Municipal Health Commission/ ; 20204Y0199, 20224044//the Clinical Special Program of Shanghai Municipal Health Commission/ ; 20204Y0199, 20224044//the Clinical Special Program of Shanghai Municipal Health Commission/ ; 20204Y0199, 20224044//the Clinical Special Program of Shanghai Municipal Health Commission/ ; 20204Y0199, 20224044//the Clinical Special Program of Shanghai Municipal Health Commission/ ; 20204Y0199, 20224044//the Clinical Special Program of Shanghai Municipal Health Commission/ ; },
mesh = {Humans ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Cell Survival/drug effects ; *Apoptosis/drug effects ; Macular Degeneration/metabolism ; Vitamins/pharmacology ; Vitamin D/pharmacology ; Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; Cells, Cultured ; Sirtuin 1/metabolism/genetics ; Cellular Senescence/drug effects ; Cell Line ; Hydrogen Peroxide/pharmacology/toxicity ; },
abstract = {BACKGROUND: Oxidative stress-induced retinal pigment epithelium (RPE) cell damage is a major factor in age-related macular degeneration (AMD). Vitamin D3 (VD3) is a powerful antioxidant and it has been suggested to have anti-aging properties and potential for treating AMD. This study aimed to investigate the effect of VD3 on RPE cell oxidative apoptosis of RPE cells in order to provide experimental evidence for the treatment of AMD.<br><br>METHODS: Human retinal pigment epithelial cell 19 (ARPE-19) cells were divided into four groups: blank group (untreated), model group (incubated in medium with 400&#xa0;&#x3bc;mol/L H2O2 for 1&#xa0;h), VD3 group (incubated in medium with 100&#xa0;&#x3bc;mol/L VD3 for 24&#xa0;h), and treatment group (incubated in medium with 400&#xa0;&#x3bc;mol/L H2O2 for 1&#xa0;h and 100&#xa0;&#x3bc;mol/L VD3 for 24&#xa0;h). Cell viability, cell senescence, ROS content, expression levels of vitamin D specific receptors, Akt, Sirt1, NAMPT, and JNK mRNA expression levels, SOD activity, and MDA, GSH, and GPX levels were measured.<br><br>RESULTS: We first established an ARPE-19 cell stress model with H2O2. Our control experiment showed that VD3 treatment had no significant effect on ARPE-19 cell viability within 6-48&#xa0;h. Treating the stressed ARPE-19 cells with VD3 showed mixed results; caspase-3 expression was decreased, Bcl-2 expression was increased, MDA level of ARPE-19 cells was decreased, GSH-PX, GPX and SOD levels were increased, the relative mRNA expression levels of Akt, Sirt1, NAMPT were increased (P&#x2009;<&#x2009;0.05), and the relative mRNA expression level of JNK was decreased (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: VD3 can potentially slow the development of AMD.},
}
@article {pmid38964658,
year = {2024},
author = {Dong, XX and Chen, DL and Miao, YF and Li, DL and Kai, JY and Hu, DN and Zhang, XF and Carla, L and Andrzej, G and Pan, CW},
title = {The impact of 25-hydroxyvitamin D and calcium on risk of age-related macular degeneration: a Mendelian randomization study.},
journal = {The American journal of clinical nutrition},
volume = {120},
number = {3},
pages = {727-736},
doi = {10.1016/j.ajcnut.2024.06.018},
pmid = {38964658},
issn = {1938-3207},
mesh = {Humans ; *Vitamin D/analogs &amp; derivatives/blood ; *Macular Degeneration/genetics/blood/epidemiology ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; Calcium/blood ; Calcium, Dietary/administration &amp; dosage ; Dietary Supplements ; Risk Factors ; Polymorphism, Single Nucleotide ; Female ; Aged ; },
abstract = {BACKGROUND: The relationships between 25-hydroxyvitamin D [25(OH)D] and calcium and age-related macular degeneration (AMD) are unclear.<br><br>OBJECTIVES: This study aimed to investigate the causal role of 25(OH)D concentrations, calcium concentrations, and dietary supplements use of vitamin D and calcium on risk of AMD and its subtypes.<br><br>METHODS: Independent genetic variants associated with 25(OH)D and calcium concentrations were used as instrumental variables in published genome-wide association studies (GWASs) of European ancestry. The bidirectional 2-sample Mendelian randomization (MR) analyses were performed using summary-level data from the UK Biobank and FinnGen datasets. Sensitivity analyses were conducted to ensure the robustness of the MR results. The meta-analyses were conducted using both fixed-effect and random-effect models to provide comprehensive and reliable estimates.<br><br>RESULTS: A standard deviation increase in calcium concentrations was linked to a 14%, 17%, and 13% reduction in the likelihood of developing AMD (95% confidence interval [CI]: 0.77, 0.97), wet AMD (95% CI: 0.73, 0.95), and dry AMD (95% CI: 0.75, 1.00), respectively. No significant causal relationships were detected between genetically predicted 25(OH)D concentrations and AMD and its subtypes (all P > 0.05). The combined analyses showed that higher calcium concentrations were associated with a reduced risk of overall AMD, with an odds ratio of 0.89 (95% CI: 0.81, 0.98).<br><br>CONCLUSIONS: This study provides evidence supporting the causal relationship between calcium concentrations and risk of AMD and its subtypes, which may have important implications for the prevention, monitoring, and treatment of AMD.},
}
@article {pmid38963653,
year = {2024},
author = {Kızılay, ME and Şengün, GD and Esen, F and Durmuş, E and Oğuz, H and Aykut, V},
title = {Factors affecting prognosis and need for anti-vascular endothelial growth factor injections in wet age-related macular degeneration.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {312},
pmid = {38963653},
issn = {1573-2630},
mesh = {Humans ; Male ; *Intravitreal Injections ; Retrospective Studies ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; Aged ; *Ranibizumab/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Bevacizumab/administration &amp; dosage ; *Tomography, Optical Coherence/methods ; Prognosis ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To understand factors affecting visual prognosis and the number of intravitreal antivascular endothelial growth factor (anti-VEGF) injections needed to stabilize wet age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective cohort, 119 treatment-na&#xef;ve wet AMD patients were followed for two years. In patients with bilateral disease, the eye with worse best-corrected visual acuity (BCVA) or that received more intravitreal injections was recruited as the study eye. In all visits, BCVA was recorded, ophthalmological examination was performed including macular optical coherence tomography imaging. Twenty health status/lifestyle questions were asked to the patients via phone as potential risk factors. All patients received 3 loading doses of intravitreal bevacizumab injections and received repeat injections of aflibercept or ranibizumab when the eye had a new, active neovascular lesion.<br><br>RESULTS: Patients who took regular micronutrition had similar visual outcome and injection numbers compared to the ones who did not. Patients with bilateral disease needed less intravitreal injections compared to unilateral AMD patients (p&#x2009;=&#x2009;0.016) and women on hormone replacement therapy (HRT) required less injections compared to the women who were not (p&#x2009;=&#x2009;0.024). Female patients had a mean gain of 2.7 letters while male patients lost 3.8 letters (p&#x2009;=&#x2009;0.038). Wet AMD started at an earlier age in smokers (p&#x2009;=&#x2009;0.002). Patients with a better education level presented earlier with better BCVA (p&#x2009;=&#x2009;0.037).<br><br>CONCLUSION: HRT and anti-VEGF injections to the fellow eye improved the prognosis of wet AMD, while male patients had slightly worse prognosis. Estrogen's protective effects and potential contribution in wet AMD needs further attention. Retrospectively registered: 2020/0622.},
}
@article {pmid38962280,
year = {2024},
author = {Hampton, C and Bharti, K and Song, MJ},
title = {Tissue Engineering of Outer Blood Retina Barrier for Therapeutic Development.},
journal = {Current opinion in biomedical engineering},
volume = {31},
number = {},
pages = {},
pmid = {38962280},
issn = {2468-4511},
support = {ZIA EY000559/ImNIH/Intramural NIH HHS/United States ; ZIA TR000399/ImNIH/Intramural NIH HHS/United States ; },
abstract = {Age related macular degeneration and other retinal degenerative disorders are characterized by disruption of the outer blood retinal barrier (oBRB) with subsequent ischemia, neovascularization, and atrophy. Despite the treatment advances, there remains no curative therapy, and no treatment targeted at regenerating native-like tissue for patients with late stages of the disease. Here we present advances in tissue engineering, focusing on bioprinting methods of generating tissue allowing for safe and reliable production of oBRB as well as tissue reprogramming with induced pluripotent stem cells for transplantation. We compare these approaches to organ-on-a-chip models for studying the dynamic nature of physiologic conditions. Highlighted within this review are studies that employ good manufacturing practices and use clinical grade methods that minimize potential risk to patients. Lastly, we illustrate recent clinical applications demonstrating both safety and efficacy for direct patient use. These advances provide an avenue for drug discovery and ultimately transplantation.},
}
@article {pmid38961279,
year = {2024},
author = {Bai, T and Cui, B and Xing, M and Chen, S and Zhu, Y and Lin, D and Guo, Y and Du, M and Wang, X and Zhou, D and Yan, H},
title = {Stable inhibition of choroidal neovascularization by adeno-associated virus 2/8-vectored bispecific molecules.},
journal = {Gene therapy},
volume = {31},
number = {9-10},
pages = {511-523},
pmid = {38961279},
issn = {1476-5462},
mesh = {*Choroidal Neovascularization/therapy ; Animals ; *Dependovirus/genetics ; Mice ; *Genetic Therapy/methods ; *Genetic Vectors/administration &amp; dosage/genetics ; Nerve Growth Factors/genetics/metabolism ; Eye Proteins/genetics/metabolism/pharmacology ; Vascular Endothelial Growth Factor Receptor-1/genetics/metabolism ; CD59 Antigens/genetics/metabolism ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Parvovirinae/genetics ; Macular Degeneration/therapy ; Serpins ; },
abstract = {Neovascular age-related macular degeneration (nAMD) causes severe visual impairment. Pigment epithelium-derived factor (PEDF), soluble CD59 (sCD59), and soluble fms-like tyrosine kinase-1 (sFLT-1) are potential therapeutic agents for nAMD, which target angiogenesis and the complement system. Using the AAV2/8 vector, two bi-target gene therapy agents, AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59, were generated, and their therapeutic efficacy was investigated in laser-induced choroidal neovascularization (CNV) and Vldlr[-/-] mouse models. After a single injection, AAV2/8-mediated gene expression was maintained at high levels in the retina for two months. Both AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 significantly reduced CNV development for an extended period without side effects and provided efficacy similar to two injections of current anti-vascular endothelial growth factor monotherapy. Mechanistically, these agents suppressed the extracellular signal-regulated kinase and nuclear factor-κB pathways, resulting in anti-angiogenic activity. This study demonstrated the safety and long-lasting effects of AAV2/8-PEDF-P2A-sCD59 and AAV2/8-sFLT-1-P2A-sCD59 in CNV treatment, providing a promising therapeutic strategy for nAMD.},
}
@article {pmid38959721,
year = {2024},
author = {de Vente, C and van Ginneken, B and Hoyng, CB and Klaver, CCW and Sánchez, CI},
title = {Uncertainty-aware multiple-instance learning for reliable classification: Application to optical coherence tomography.},
journal = {Medical image analysis},
volume = {97},
number = {},
pages = {103259},
doi = {10.1016/j.media.2024.103259},
pmid = {38959721},
issn = {1361-8423},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Deep Learning ; Uncertainty ; Reproducibility of Results ; Artifacts ; Image Processing, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging ; Algorithms ; },
abstract = {Deep learning classification models for medical image analysis often perform well on data from scanners that were used to acquire the training data. However, when these models are applied to data from different vendors, their performance tends to drop substantially. Artifacts that only occur within scans from specific scanners are major causes of this poor generalizability. We aimed to enhance the reliability of deep learning classification models using a novel method called Uncertainty-Based Instance eXclusion (UBIX). UBIX is an inference-time module that can be employed in multiple-instance learning (MIL) settings. MIL is a paradigm in which instances (generally crops or slices) of a bag (generally an image) contribute towards a bag-level output. Instead of assuming equal contribution of all instances to the bag-level output, UBIX detects instances corrupted due to local artifacts on-the-fly using uncertainty estimation, reducing or fully ignoring their contributions before MIL pooling. In our experiments, instances are 2D slices and bags are volumetric images, but alternative definitions are also possible. Although UBIX is generally applicable to diverse classification tasks, we focused on the staging of age-related macular degeneration in optical coherence tomography. Our models were trained on data from a single scanner and tested on external datasets from different vendors, which included vendor-specific artifacts. UBIX showed reliable behavior, with a slight decrease in performance (a decrease of the quadratic weighted kappa (κw) from 0.861 to 0.708), when applied to images from different vendors containing artifacts; while a state-of-the-art 3D neural network without UBIX suffered from a significant detriment of performance (κw from 0.852 to 0.084) on the same test set. We showed that instances with unseen artifacts can be identified with OOD detection. UBIX can reduce their contribution to the bag-level predictions, improving reliability without retraining on new data. This potentially increases the applicability of artificial intelligence models to data from other scanners than the ones for which they were developed. The source code for UBIX, including trained model weights, is publicly available through https://github.com/qurAI-amsterdam/ubix-for-reliable-classification.},
}
@article {pmid38955757,
year = {2024},
author = {Zhang, M and Liao, Q and Yang, TT},
title = {[The innovation and challenge of artificial intelligence in the whole process management of fundus disease].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {60},
number = {7},
pages = {559-565},
doi = {10.3760/cma.j.cn112142-20240410-00171},
pmid = {38955757},
issn = {0412-4081},
mesh = {Humans ; *Artificial Intelligence ; *Retinal Diseases/therapy ; Fundus Oculi ; Diabetic Retinopathy/therapy/diagnosis ; Algorithms ; Telemedicine ; Macular Degeneration/therapy ; },
abstract = {Artificial intelligence (AI) has demonstrated revolutionary potential and wide-ranging applications in the comprehensive management of fundus diseases, yet it faces challenges in clinical translation, data quality, algorithm interpretability, and cross-cultural adaptability. AI has proven effective in the efficient screening, accurate diagnosis, personalized treatment recommendations, and prognosis prediction for conditions such as diabetic retinopathy, age-related macular degeneration, and other fundus diseases. However, there is a significant gap between the need for large-scale, high-quality, and diverse datasets and the limitations of current research data. Additionally, the black-box nature of AI algorithms, the acceptance by clinicians and patients, and the generalizability of these algorithms pose barriers to their widespread clinical adoption. Researchers are addressing these challenges through approaches such as federated learning, standardized data collection, and prospective trials to enhance the robustness, interpretability, and practicality of AI systems. Despite these obstacles, the benefits of AI in fundus disease management are substantial. These include improved screening efficiency, support for personalized treatment, the discovery of novel disease characteristics, and the development of precise treatment strategies. Moreover, AI facilitates the advancement of telemedicine through 5G and the Internet of Things. Future research should continue to tackle existing issues, fully leverage the potential of AI in the prevention and treatment of fundus diseases, and advance intelligent, precise, and remote ophthalmic services to meet global eye health needs.},
}
@article {pmid38955261,
year = {2024},
author = {Stark, AK and Penn, JS},
title = {Prostanoid signaling in retinal vascular diseases.},
journal = {Prostaglandins &amp; other lipid mediators},
volume = {174},
number = {},
pages = {106864},
pmid = {38955261},
issn = {1098-8823},
support = {F31 EY034386/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Prostaglandins/metabolism ; *Signal Transduction ; *Retinal Diseases/metabolism/drug therapy ; Animals ; Retinal Vessels/metabolism/pathology ; },
abstract = {The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.},
}
@article {pmid38954771,
year = {2024},
author = {von Lintig, J and Bandara, S},
title = {The Absorption, Storage, and Transport of Ocular Carotenoids and Retinoids.},
journal = {Annual review of vision science},
volume = {10},
number = {1},
pages = {323-346},
pmid = {38954771},
issn = {2374-4650},
support = {R01 EY020551/EY/NEI NIH HHS/United States ; R01 EY028121/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinoids/metabolism ; *Carotenoids/metabolism ; Animals ; Biological Transport/physiology ; Retina/metabolism ; *Eye/metabolism ; },
abstract = {Carotenoids, yellow and red pigments found abundantly in nature, play essential roles in various aspects of human physiology. They serve as critical molecules in vision by functioning as antioxidants and as filters for blue light within the retina. Furthermore, carotenoids are the natural precursors of vitamin A, which is indispensable for the synthesis of retinaldehyde, the visual chromophore, and retinoic acid, a small molecule that regulates gene expression. Insufficient levels of carotenoids and retinoids have been linked to age-related macular degeneration and xerophthalmia, respectively. Nevertheless, the mechanisms by which the eye maintains carotenoid and retinoid homeostasis have remained a mystery. Recent breakthroughs identified the molecular players involved in this process and provided valuable biochemical insights into their functioning. Mutations in the corresponding genes disrupt the homeostasis of carotenoids and retinoids, leading to visual system pathologies. This review aims to consolidate our current understanding of these pathways, including their regulatory principles.},
}
@article {pmid38954231,
year = {2024},
author = {Tuo, S and Jiang, J},
title = {A Novel Detection Method for High-Order SNP Epistatic Interactions Based on Explicit-Encoding-Based Multitasking Harmony Search.},
journal = {Interdisciplinary sciences, computational life sciences},
volume = {16},
number = {3},
pages = {688-711},
pmid = {38954231},
issn = {1867-1462},
support = {62276210//National Natural Science Foundation of China/ ; },
mesh = {*Polymorphism, Single Nucleotide/genetics ; *Epistasis, Genetic ; *Algorithms ; Humans ; *Bayes Theorem ; Machine Learning ; Multifactor Dimensionality Reduction ; Computational Biology/methods ; Genetic Predisposition to Disease ; },
abstract = {To elucidate the genetic basis of complex diseases, it is crucial to discover the single-nucleotide polymorphisms (SNPs) contributing to disease susceptibility. This is particularly challenging for high-order SNP epistatic interactions (HEIs), which exhibit small individual effects but potentially large joint effects. These interactions are difficult to detect due to the vast search space, encompassing billions of possible combinations, and the computational complexity of evaluating them. This study proposes a novel explicit-encoding-based multitasking harmony search algorithm (MTHS-EE-DHEI) specifically designed to address this challenge. The algorithm operates in three stages. First, a harmony search algorithm is employed, utilizing four lightweight evaluation functions, such as Bayesian network and entropy, to efficiently explore potential SNP combinations related to disease status. Second, a G-test statistical method is applied to filter out insignificant SNP combinations. Finally, two machine learning-based methods, multifactor dimensionality reduction (MDR) as well as random forest (RF), are employed to validate the classification performance of the remaining significant SNP combinations. This research aims to demonstrate the effectiveness of MTHS-EE-DHEI in identifying HEIs compared to existing methods, potentially providing valuable insights into the genetic architecture of complex diseases. The performance of MTHS-EE-DHEI was evaluated on twenty simulated disease datasets and three real-world datasets encompassing age-related macular degeneration (AMD), rheumatoid arthritis (RA), and breast cancer (BC). The results demonstrably indicate that MTHS-EE-DHEI outperforms four state-of-the-art algorithms in terms of both detection power and computational efficiency. The source code is available at https://github.com/shouhengtuo/MTHS-EE-DHEI.git .},
}
@article {pmid38953649,
year = {2024},
author = {Rowe, LW and Ciulla, TA},
title = {Long-acting delivery and therapies for neovascular age-related macular degeneration.},
journal = {Expert opinion on biological therapy},
volume = {24},
number = {8},
pages = {799-814},
doi = {10.1080/14712598.2024.2374869},
pmid = {38953649},
issn = {1744-7682},
mesh = {Humans ; Animals ; *Macular Degeneration/genetics/metabolism/therapy ; Neovascularization, Pathologic ; Drug Delivery Systems ; Genetic Therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life.<br><br>AREAS COVERED: This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained-release polymers and devices, reservoirs for intravitreal delivery, suprachoroidal delivery of small molecular suspensions and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed.<br><br>EXPERT OPINION: The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high-dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes, demonstrating promise in expanding treatment durability.},
}
@article {pmid38953555,
year = {2024},
author = {Shoda, C and Lee, D and Miwa, Y and Yamagami, S and Nakashizuka, H and Nimura, K and Okamoto, K and Kawagishi, H and Negishi, K and Kurihara, T},
title = {Inhibition of hypoxia-inducible factors suppresses subretinal fibrosis.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {38},
number = {13},
pages = {e23792},
doi = {10.1096/fj.202400540RRR},
pmid = {38953555},
issn = {1530-6860},
support = {18K09424//KAKENHI/ ; 24K12770//KAKENHI/ ; //Development of Research Seeds Based on Marine Biotechnology from Shizuoka Prefecture/ ; JPMJSP2123//JST SPRING/ ; JP22gm1510007//AMED/ ; },
mesh = {Animals ; Mice ; *Fibrosis/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *Von Hippel-Lindau Tumor Suppressor Protein/metabolism/genetics ; *Mice, Knockout ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics/antagonists &amp; inhibitors ; Basic Helix-Loop-Helix Transcription Factors/metabolism/genetics/antagonists &amp; inhibitors ; Macular Degeneration/metabolism/pathology/drug therapy ; Retina/metabolism/pathology ; Epithelial-Mesenchymal Transition/drug effects ; Mice, Inbred C57BL ; },
abstract = {Age-related macular degeneration (AMD) is a common cause of vision loss. The aggressive form of AMD is associated with ocular neovascularization and subretinal fibrosis, representing a responsive outcome against neovascularization mediated by epithelial-mesenchymal transition of retinal pigment epithelium (RPE) cells. A failure of the current treatment (anti-vascular endothelial growth factor therapy) has also been attributed to the progression of subretinal fibrosis. Hypoxia-inducible factors (HIFs) increase gene expressions to promote fibrosis and neovascularization. HIFs act as a central pathway in the pathogenesis of AMD. HIF inhibitors may suppress ocular neovascularization. Nonetheless, further investigation is required to unravel the aspects of subretinal fibrosis. In this study, we used RPE-specific HIFs or von Hippel-Lindau (VHL, a regulator of HIFs) conditional knockout (cKO) mice, along with pharmacological HIF inhibitors, to demonstrate the suppression of subretinal fibrosis. Fibrosis was suppressed by treatments of HIF inhibitors, and similar suppressive effects were detected in RPE-specific Hif1a/Hif2a- and Hif1a-cKO mice. Promotive effects were observed in RPE-specific Vhl-cKO mice, where fibrosis-mediated pathologic processes were evident. Marine products' extracts and their component taurine suppressed fibrosis as HIF inhibitors. Our study shows critical roles of HIFs in the progression of fibrosis, linking them to the potential development of therapeutics for AMD.},
}
@article {pmid38952896,
year = {2024},
author = {Qu, Y and Zhang, G and Wu, Z and Luo, H and Chen, R and Jia, H and Sun, X},
title = {Associations of Socioeconomic Status Inequity with Incident Age-related Macular Degeneration in Middle-Aged and Elderly Population.},
journal = {Health data science},
volume = {4},
number = {},
pages = {0148},
pmid = {38952896},
issn = {2765-8783},
abstract = {Background: The relationship between socioeconomic status (SES) inequity and incident age-related macular degeneration (AMD) remains unclear. We aim to investigate whether low SES increases the risk of AMD and to explore the effect of a healthy lifestyle on this association. Methods: This prospective cohort study included 316,663 UK Biobank individuals. SES inequity was identified via latent class analysis using education, household income, and occupational status. Healthy lifestyle score was calculated based on smoking, alcohol drinking, and physical activity (PA). Incident AMD was defined according to diagnosis records. Cox proportional hazards models were used to evaluate the relationship of low SES and AMD. Interrelationships of healthy lifestyle score on SES-AMD association were explored, including modification, mediation, and joint effects. Results: During the average 12.2 years of follow-up, 6,355 AMD cases were diagnosed. Participants with medium SES (hazard ratio: 1.10 [95% confidence interval (CI) 1.01 to 1.21]) and low SES (hazard ratio: 1.22 [95% CI 1.11 to 1.34]) had an increased risk of incident AMD compared to participants with high SES. PA significantly affected this association. Moreover, the association between low SES and AMD was significantly mediated (11.3%, 95% CI: 6.56 to 23.0) by smoking. Similarly, alcohol drinking suppressed (9.59%, 95% CI: 4.00 to 23.2) the association between high SES and AMD. Besides, a significant joint effect of SES and healthy lifestyle score was found. Conclusions: We provide further evidence for the relationship of socioeconomic inequity, healthy lifestyle, and incident AMD. Future public health strategies should aim to reduce socioeconomic inequity to prevent AMD.},
}
@article {pmid38952481,
year = {2024},
author = {Nyenga, AM and Kayembe Mbuyu, A and Lubala, TK},
title = {Intracerebral Calcifications Associated with Failure to Thrive and Macular Degeneration in an Adolescent: A Case Report.},
journal = {International medical case reports journal},
volume = {17},
number = {},
pages = {627-633},
pmid = {38952481},
issn = {1179-142X},
abstract = {BACKGROUND: The clinical picture of intracerebral calcification is so varied that it constitutes an essential element of a wide range of clinical syndromes of variable expression that continue to be described. In this article, we discuss the diagnostic possibilities of basal ganglia calcification considering the association of failure to thrive and macular degeneration in our patient.<br><br>CASE: A 17-year-old male patient of Congolese origin consulted us for a pyramidal syndrome consisting of upper limb tremors during mobilization and dysgraphia. The patient also presented with a distance vision disorder for which the ophthalmological examination revealed poor visual acuity in both eyes (2/10) and macular degeneration in the left eye. On physical examination, we noted a short stature with a small head circumference in relation to age. The brain scan revealed the presence of bilateral striato-pallidal calcifications giving the appearance of Fahr's disease. However, the association of delay of stature development with microcrania, macular degeneration with reduced visual acuity and basal ganglia calcifications could suggest a wide range of syndromic hypotheses, the most likely of which is Rajab-type cerebral calcification.<br><br>CONCLUSION: The association of failure to thrive, macular degeneration, and cerebral calcification of the basal ganglia is revealed as a particular phenotype compared to cases reported in the literature. An in-depth analysis would be necessary to identify a possible genetic basis.},
}
@article {pmid38952394,
year = {2024},
author = {Zheng, Z and Yu, X},
title = {Insulin resistance in the retina: possible implications for certain ocular diseases.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1415521},
pmid = {38952394},
issn = {1664-2392},
mesh = {Humans ; *Insulin Resistance/physiology ; Retina/metabolism/pathology ; Diabetic Retinopathy/metabolism ; Animals ; Retinal Diseases/metabolism ; Eye Diseases/metabolism/etiology ; Oxidative Stress/physiology ; Macular Degeneration/metabolism ; Glaucoma/metabolism/physiopathology ; Risk Factors ; },
abstract = {Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence has demonstrated a strong relationship between IR and a higher incidence of several dramatically vision-threatening retinal diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. In this review, we provide a schematic overview of the associations between IR and certain ocular diseases and further explore the possible mechanisms. Although the exact causes explaining these associations have not been fully elucidated, underlying mechanisms of oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vasoconstriction, and neurodegenerative impairments may be involved. Given that IR is a modifiable risk factor, it may be important to identify patients at a high IR level with prompt treatment, which may decrease the risk of developing certain ocular diseases. Additionally, improving IR through the activation of insulin signaling pathways could become a potential therapeutic target.},
}
@article {pmid38951820,
year = {2024},
author = {Han, G and Wei, P and He, M and Jia, L and Su, Q and Yang, X and Hao, R},
title = {Role of plasma fatty acid in age-related macular degeneration: insights from a mendelian randomization analysis.},
journal = {Lipids in health and disease},
volume = {23},
number = {1},
pages = {206},
pmid = {38951820},
issn = {1476-511X},
support = {82301240//National Natural Science Foundation of China/ ; 21JCQNJC01800//Natural Science Foundation of Tianjin Municipality/ ; TJWJ2022QN079, TJWJ2023MS0036//Tianjin Health and Technology Project/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Macular Degeneration/blood/genetics ; *Fatty Acids, Omega-3/blood ; *Genome-Wide Association Study ; Male ; *Delta-5 Fatty Acid Desaturase ; Female ; *Fatty Acids, Omega-6/blood ; Aged ; *Polymorphism, Single Nucleotide ; Fatty Acid Desaturases/genetics ; Middle Aged ; Triglycerides/blood ; Fatty Acids/blood ; Risk Factors ; },
abstract = {BACKGROUND: An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes.<br><br>METHODS: We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides.<br><br>RESULTS: Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66-0.92) and dry AMD (0.85, 0.74-0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03-1.56) and dry AMD (1.18, 1.02-1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82-0.98; FADS2, 0.88, 0.81-0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02-1.20; FADS2, 1.11, 1.03-1.20) suggests causal effects of these factors on wet AMD.<br><br>CONCLUSIONS: The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.},
}
@article {pmid38951350,
year = {2024},
author = {Wu, J and Wang, Y and Zhang, M and Sun, X},
title = {Publication trends of vascular endothelial growth factor (VEGF) and anti-VEGF treatment in neovascular age-related macular degeneration during 2001-2020: a 20-year bibliometric study.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {295},
pmid = {38951350},
issn = {1573-2630},
support = {22YF1435500//Shanghai Sailing Program/ ; 82171076//National Natural Science&#xa0;Foundation of China/ ; },
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Bibliometrics ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; },
abstract = {PURPOSE: This study sought to provide an overview of the current research and further analyze publication trends in the field of vascular endothelial growth factor (VEGF) and anti-VEGF treatment for neovascular age-related macular degeneration (NVAMD).<br><br>METHODS: We downloaded all related publications from 2001 to 2020 from the Web of Science Core Collection and conducted a bibliometric analysis using the bibiometrix package in R programming software.<br><br>RESULTS: A total of 3717 publications were included in the analysis. The USA contributed the largest number of publications (1443), and achieved the highest number of citations (74,946) and H-index value (28). Johns Hopkins University, USA, was the top institution with the most publications, and Peter A. Campochiaro was the most productive professor at The Wilmer Eye Institute, USA. 9.60% of the total publications were from the Journal of Retinal and Vitreous Diseases. Trend analysis demonstrated that anti-VEGF therapy was introduced in early 2000 after steroids, and the last 2&#xa0;decades have witnessed the blossom of several anti-VEGF agents. "Treat-and-extend" and "resistance" were two popular trend topics in recent years.<br><br>CONCLUSIONS: The USA occupies a dominant position in the research field of VEGF and anti-VEGF treatments in NVAMD. Steroid administration, photodynamic therapy, and anti-VEGF therapy have been pivotal advances in the treatment of NVAMD patients over the past 2&#xa0;decades. Limited acting period and resistance are potential investigation directions in future studies.},
}
@article {pmid38948341,
year = {2024},
author = {Chakraborty, D and Boral, S and Sinha, TK and Das, A and Mukherjee, A and Majumdar, S and Bhattacharya, R and Maitra, R},
title = {Transitioning from Aflibercept to Biosimilar Ranibizumab in Neovascular AMD (The TRANSFORM Trial): A Multicenter Observational Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {1819-1828},
pmid = {38948341},
issn = {1177-5467},
abstract = {PURPOSE: This study investigates the efficacy of transitioning patients with neovascular age-related macular degeneration (nAMD) from aflibercept (T1) to biosimilar ranibizumab (T2), an approach not previously documented in literature.<br><br>METHODS: In this multicenter observational study, patients over 50 years of age with nAMD were shifted from intravitreal aflibercept (IVI AFL) to biosimilar ranibizumab (B-RBZ) due to financial constraints. This study employed standardized ophthalmological methods to assess visual acuity (VA), central macular thickness (CMT), and subretinal and intraretinal fluid. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and linear regression.<br><br>RESULTS: A total of 29 eyes (12 males and 17 females) were analyzed. Mean age was 72.55 &#xb1;6.43 years. VA improved significantly during T1, with a mean increase from 55.0 &#xb1; 10.2 to 70.0 &#xb1; 8.5 ETDRS letters at the switch time point (p < 0.01), then a slight decrease to 62.3 &#xb1; 8.9 at 12 months (p < 0.05) was noted during T2. The mean CMT decreased notably from 400 &#xb1; 50 to 290 &#xb1; 45 &#x3bc;m at the switch. The final CMT at 12 months after switching to B-RBZ was 280 &#xb1; 40 &#x3bc;m (p < 0.01). There was a significant decrease in the retinal and intra retinal fluid during T1, followed by a gradual increase during T2. A significant correlation (p < 0.05) was noted between the presence of intraretinal fluid and increased injection frequency of B-RBZ.<br><br>CONCLUSION: The switch from IVI AFL to IVI B-RBZ in patients with nAMD demonstrated efficacy in maintaining the VA and macular anatomy, with some challenges in fluid management.},
}
@article {pmid38945517,
year = {2024},
author = {Lunding, BS and Bassi, MR and Christensen, JP and Thomsen, AR and Sørensen, TL and Vorum, H and Honoré, B and Nissen, MH and Steffensen, MA},
title = {Systemic infection in aged mice causes upregulation of crystallin alpha A in the RPE/choroid.},
journal = {Experimental eye research},
volume = {245},
number = {},
pages = {109984},
doi = {10.1016/j.exer.2024.109984},
pmid = {38945517},
issn = {1096-0007},
mesh = {Animals ; Mice ; *Up-Regulation ; *Choroid/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Aging ; *Mice, Inbred C57BL ; *Macular Degeneration/metabolism/genetics ; Disease Models, Animal ; Blotting, Western ; Eye Infections, Viral/metabolism/virology ; Real-Time Polymerase Chain Reaction ; },
abstract = {Aging changes the responsiveness of our immune defense, and this decline in immune reactivity plays an important role in the increased susceptibility to infections that marks progressing age. Aging is also the most pronounced risk factor for development of age-related macular degeneration (AMD), a disease that is characterized by dysfunctional retinal pigment epithelial (RPE) cells and loss of central vision. We have previously shown that acute systemic viral infection has a large impact on the retina in young mice, leading to upregulation of chemokines in the RPE/choroid (RPE/c) and influx of CD8 T cells in the neuroretina. In this study, we sought to investigate the impact of systemic infection on the RPE/c in aged mice to evaluate whether infection in old age could play a role in the pathogenesis of AMD. We found that systemic infection in mice led to upregulation of genes from the crystallin family in the RPE/c from aged mice, but not in the RPE/c from young mice. Crystallin alpha A (CRYAA) was the most upregulated gene, and increased amounts of CRYAA protein were also detected in the aged RPE/c. Increased CRYAA gene and protein expression has previously been found in drusen and choroid from AMD patients, and this protein has also been linked to neovascularization. Since both drusen and neovascularization are important hallmarks of advanced AMD, it is interesting to speculate if upregulation of crystallins in response to infection in old age could be relevant for the pathogenesis of AMD.},
}
@article {pmid38944776,
year = {2024},
author = {Trofimova, AA and Kudryavtsev, AV and Postoev, VA and Zelentsov, RN and Novikova, IA and Sannikov, AL},
title = {[Association between emotional disorders and ophthalmopathology in residents of the Arkhangelsk region at the age of 60-74 years.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {37},
number = {1-2},
pages = {72-79},
pmid = {38944776},
issn = {1561-9125},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Russia/epidemiology ; *Anxiety/epidemiology/diagnosis/psychology ; Visual Acuity ; Depression/epidemiology/diagnosis/psychology/etiology ; Eye Diseases/epidemiology/diagnosis/psychology/physiopathology ; Surveys and Questionnaires ; Vision Disorders/epidemiology/psychology/physiopathology/diagnosis ; },
abstract = {A study was conducted to investigate the associations of the diseases of the organ of vision and its accessory apparatus with anxiety and depression in the elderly people. The study included 678 participants of the ESSE-RF3 population study in the Arkhangelsk region in the age of 60-74 years. We used a questionnaire, including the hospital scale of anxiety and depression score (HADS), and the assessment of the ophthalmological status. It was found that all the study participants had diseases of the visual organ. Elevated depression scores were associated with sex, age, marital status (being single), and disability, elevated anxiety scores - with sex. The scores on the anxiety scale were on average 25% higher in participants whose visual acuity decreased to (?)0,5 units, and showed no independent associations with diagnosed ophthalmological diseases. The scores on the depression scale were on average 33% higher in participants with visual acuity (?)0,5 units, and 22% higher in the presence of retinopathy. In conclusion, anxiety and depression in the elderly people were more associated with visual deficits rather than with the presence of ophthalmological diseases underlying a decrease in functional status.},
}
@article {pmid38942133,
year = {2024},
author = {Maurya, R and Vikal, A and Narang, RK and Patel, P and Kurmi, BD},
title = {Recent advancements and applications of ophthalmic gene therapy strategies: A breakthrough in ocular therapeutics.},
journal = {Experimental eye research},
volume = {245},
number = {},
pages = {109983},
doi = {10.1016/j.exer.2024.109983},
pmid = {38942133},
issn = {1096-0007},
mesh = {Humans ; *Genetic Therapy/methods ; *Genetic Vectors ; Eye Diseases/therapy/genetics ; Gene Transfer Techniques ; Retinal Diseases/therapy/genetics ; Animals ; },
abstract = {Over the past twenty years, ocular gene therapy has primarily focused on addressing diseases linked to various genetic factors. The eye is an ideal candidate for gene therapy due to its unique characteristics, such as easy accessibility and the ability to target both corneal and retinal conditions, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), age-related macular degeneration (AMD), and Stargardt disease. Currently, literature documents 33 clinical trials in this field, with the most promising results emerging from trials focused on LCA. These successes have catalyzed further research into other ocular conditions such as glaucoma, AMD, RP, and choroideremia. The effectiveness of gene therapy relies on the efficient delivery of genetic material to specific cells, ensuring sustained and optimal gene expression over time. Viral vectors have been widely used for this purpose, although concerns about potential risks such as immune reactions and genetic mutations have led to the development of non-viral vector systems. Preliminary laboratory research and clinical investigations have shown a connection between vector dosage and the intensity of immune response and inflammation in the eye. The method of administration significantly influences these reactions, with subretinal delivery resulting in a milder humoral response compared to the intravitreal route. This review discusses various ophthalmic diseases, including both corneal and retinal conditions, and their underlying mechanisms, highlighting recent advances and applications in ocular gene therapies.},
}
@article {pmid38935351,
year = {2024},
author = {Freund, KB and Bijon, J and Ramtohul, P},
title = {Dosing vs Assessment Intervals With Faricimab and Aflibercept.},
journal = {JAMA ophthalmology},
volume = {142},
number = {8},
pages = {697-698},
doi = {10.1001/jamaophthalmol.2024.2209},
pmid = {38935351},
issn = {2168-6173},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; Drug Administration Schedule ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Wet Macular Degeneration/drug therapy ; Male ; },
}
@article {pmid38935031,
year = {2024},
author = {Chen, Y and Yang, S and Liu, R and Xiong, R and Wang, Y and Li, C and Zheng, Y and He, M and Wang, W},
title = {Forecasting Myopic Maculopathy Risk Over a Decade: Development and Validation of an Interpretable Machine Learning Algorithm.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {6},
pages = {40},
pmid = {38935031},
issn = {1552-5783},
mesh = {Humans ; Male ; Female ; Middle Aged ; Adult ; *Machine Learning ; *Tomography, Optical Coherence/methods ; Aged ; *Disease Progression ; *Algorithms ; Adolescent ; Child ; Young Adult ; *Macular Degeneration/diagnosis ; *Myopia, Degenerative/diagnosis ; Follow-Up Studies ; Risk Factors ; Forecasting ; Risk Assessment/methods ; Visual Acuity ; },
abstract = {PURPOSE: The purpose of this study was to develop and validate prediction model for myopic macular degeneration (MMD) progression in patients with high myopia.<br><br>METHODS: The Zhongshan High Myopia Cohort for model development included 660 patients aged 7 to 70 years with a bilateral sphere of &#x2264;-6.00 diopters (D). Two hundred twelve participants with an axial length (AL) &#x2265;25.5 mm from the Chinese Ocular Imaging Project were used for external validation. Thirty-four clinical variables, including demographics, lifestyle, myopia history, and swept source optical coherence tomography data, were analyzed. Sequential forward selection was used for predictor selection, and binary classification models were created using five machine learning algorithms to forecast the risk of MMD progression over 10 years.<br><br>RESULTS: Over a median follow-up of 10.9 years, 133 patients (20.2%) showed MMD progression in the development cohort. Among them, 69 (51.9%) developed newly-onset MMD, 11 (8.3%) developed patchy atrophy from diffuse atrophy, 54 (40.6%) showed an enlargement of lesions, and 9 (6.8%) developed plus signs. Top six predictors for MMD progression included thinner subfoveal choroidal thickness, longer AL, worse best-corrected visual acuity, older age, female gender, and shallower anterior chamber depth. The eXtreme Gradient Boosting algorithm yielded the best discriminative performance (area under the receiver operating characteristic curve [AUROC] = 0.87 &#xb1; 0.02) with good calibration in the training cohort. In a less myopic external validation group (median -5.38 D), 48 patients (22.6%) developed MMD progression over 4 years, with the model's AUROC validated at 0.80 &#xb1; 0.008.<br><br>CONCLUSIONS: Machine learning model effectively predicts MMD progression a decade ahead using clinical and imaging indicators. This tool shows promise for identifying "at-risk" high myopes for timely intervention and vision protection.},
}
@article {pmid38935028,
year = {2024},
author = {Barreto, P and Farinha, C and Coimbra, R and Cachulo, ML and Melo, JB and Lechanteur, Y and Hoyng, CB and Cunha-Vaz, J and Silva, R},
title = {Unveiling Statins and Genetics in Age-Related Macular Degeneration: The Coimbra Eye Study-Report 9.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {6},
pages = {38},
pmid = {38935028},
issn = {1552-5783},
mesh = {Humans ; Male ; Female ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Aged ; *Disease Progression ; *Macular Degeneration/genetics ; Follow-Up Studies ; Risk Factors ; Middle Aged ; Aged, 80 and over ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; },
abstract = {PURPOSE: To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between statins and genetics.<br><br>METHODS: In this analysis, 682 subjects made two visits (6.5-year follow-up) of the Coimbra Eye Study. Subjects who started taking statins at any time point between the two visits were considered. Progressors were defined as not having AMD at baseline and having any AMD at follow-up. Genetic risk scores (GRSs) were calculated individually with 52 independent variants associated with AMD. Time to progression was estimated using unadjusted Kaplan-Meier curves. An extended Cox model was used for the association between statins and GRS with the risk for AMD progression. Multiplicative and additive interactions were assessed.<br><br>RESULTS: Median survival time was 7.50 years for subjects not taking statins and 7.62 for subjects taking statins (P < 0.001). Statin intake reduced the risk for progression to AMD in 48%, adjusting for age, sex, body mass index, smoking, and diabetes (model 1) and GRS (model 2). The combined effects of not taking statins and having high GRS increased the progression risk fourfold compared to taking statins and having low GRS (hazard ratio [HR] = 4.25; 95% confidence interval [CI], 1.62-11.16; P = 0.003). For subjects not taking statins, an increased risk of progression was found for those subjects with high GRS compared to subjects with low GRS (HR = 1.80; 95% CI, 1.13-2.85; P = 0.013). No statistically significant multiplicative or additive interactions were found.<br><br>CONCLUSIONS: Statins seem to be protective against AMD progression, and genetics may play a role in treatment response.},
}
@article {pmid38930032,
year = {2024},
author = {Son, W and Sagong, M},
title = {Short-Term Real-World Outcomes of Intensive Aflibercept Injection for Refractory Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {12},
pages = {},
pmid = {38930032},
issn = {2077-0383},
support = {research grant 2023//Yeungnam University/ ; },
abstract = {Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 μm to 336.38 ± 121.67 μm at the third visit (p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution (p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.},
}
@article {pmid38929964,
year = {2024},
author = {Kim, M and Kang, JE and Park, YG},
title = {Switching from a Fixed Monthly Aflibercept Regimen to Bi-Monthly Brolucizumab in Refractory Cases of Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {12},
pages = {},
pmid = {38929964},
issn = {2077-0383},
abstract = {Background/Objectives: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. Methods: A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from monthly intravitreal aflibercept treatment to bi-monthly intravitreal brolucizumab treatment. This study evaluated changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central macular thickness (CMT), at specific times as follows: baseline before switching (T0), 2 months after switching (T1), 4 months after switching (T2), and 6 months after switching (T3). Results: The mean best-corrected visual acuity (BCVA) did not significantly change across all time points (0.52 ± 0.12, 0.48 ± 0.27, 0.48 ± 0.28, and 0.50 ± 0.27 logarithms of the minimum angle of resolution in T0, T1, T2, and T3, respectively). CMT significantly decreased after additional brolucizumab injections compared to the baseline (218.2 ± 48.6 and 207.9 ± 49.8 μm, respectively; p = 0.001). The PED height also significantly decreased from 251.0 ± 165.4 to 154.4 ± 115.65 μm (p < 0.001), with complete resolution in nine patients (28%). The mean subfoveal choroidal thickness (SFCT) before brolucizumab treatment was 262.8 ± 79.7 μm, which decreased to 233.0 ± 71.2 μm (p = 0.001) after the first injection. The final SFCT also significantly decreased after additional brolucizumab injections compared to the baseline SFCT (p = 0.012). Conclusions: Bi-monthly brolucizumab treatment proves effective for patients refractory to monthly fixed aflibercept, resulting in positive anatomical changes without significant deterioration in visual acuity. This approach provides a promising prognosis while reducing the treatment burden on refractory patients.},
}
@article {pmid38929874,
year = {2024},
author = {D'Angelo, A and Vitiello, L and Gagliardi, V and Salerno, G and De Pascale, I and Coppola, A and Abbinante, G and Pellegrino, A and Giannaccare, G},
title = {The Role of Oral Supplementation for the Management of Age-Related Macular Degeneration: A Narrative Review.},
journal = {Journal of personalized medicine},
volume = {14},
number = {6},
pages = {},
pmid = {38929874},
issn = {2075-4426},
abstract = {The majority of neurodegenerative eye disorders occur with aging and significantly impair quality of life. Age-related macular degeneration (AMD) is the third most common cause of visual impairment and blindness worldwide. One of the most important elements in the pathophysiology of neurodegenerative eye disease is certainly oxidative stress, with neuroinflammation and ocular ischemia which may also be significant factors. Antioxidants, either by food or oral supplementation, may be able to mitigate the deleterious effects of reactive oxygen species that build as a result of oxidative stress, ischemia, and inflammation. Over the past few decades, a number of research works examining the potential adjuvant impact of antioxidants in AMD have been published. In fact, there is not only more and more interest in already known molecules but also in new molecules that can help clinicians in the management of this complex multifactorial disease, such as astaxanthin and melatonin. However, while some studies showed encouraging outcomes, others were conflicting. In addition, more and more attention is also being paid to nutrition, considered a pivotal key point, especially to prevent AMD. For this reason, the purpose of this review is to analyze the main antioxidant molecules currently used as oral supplements for AMD treatment, as well as the role of diet and food intake in this ocular disease, to better understand how all these factors can improve the clinical management of AMD patients.},
}
@article {pmid38929652,
year = {2024},
author = {Radu, M and Brănișteanu, DC and Pirvulescu, RA and Dumitrescu, OM and Ionescu, MA and Zemba, M},
title = {Exploring Stem-Cell-Based Therapies for Retinal Regeneration.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {6},
pages = {},
pmid = {38929652},
issn = {2075-1729},
abstract = {The escalating prevalence of retinal diseases-notably, age-related macular degeneration and hereditary retinal disorders-poses an intimidating challenge to ophthalmic medicine, often culminating in irreversible vision loss. Current treatments are limited and often fail to address the underlying loss of retinal cells. This paper explores the potential of stem-cell-based therapies as a promising avenue for retinal regeneration. We review the latest advancements in stem cell technology, focusing on embryonic stem cells (ESCs), pluripotent stem cells (PSCs), and mesenchymal stem cells (MSCs), and their ability to differentiate into retinal cell types. We discuss the challenges in stem cell transplantation, such as immune rejection, integration into the host retina, and functional recovery. Previous and ongoing clinical trials are examined to highlight the therapeutic efficacy and safety of these novel treatments. Additionally, we address the ethical considerations and regulatory frameworks governing stem cell research. Our analysis suggests that while stem-cell-based therapies offer a groundbreaking approach to treating retinal diseases, further research is needed to ensure long-term safety and to optimize therapeutic outcomes. This review summarizes the clinical evidence of stem cell therapy and current limitations in utilizing stem cells for retinal degeneration, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt's disease.},
}
@article {pmid38929607,
year = {2024},
author = {Borrelli, E and Serafino, S and Ricardi, F and Coletto, A and Neri, G and Olivieri, C and Ulla, L and Foti, C and Marolo, P and Toro, MD and Bandello, F and Reibaldi, M},
title = {Deep Learning in Neovascular Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {6},
pages = {},
pmid = {38929607},
issn = {1648-9144},
mesh = {Humans ; *Deep Learning ; *Macular Degeneration ; *Tomography, Optical Coherence/methods ; },
abstract = {Background and objectives: Age-related macular degeneration (AMD) is a complex and multifactorial condition that can lead to permanent vision loss once it progresses to the neovascular exudative stage. This review aims to summarize the use of deep learning in neovascular AMD. Materials and Methods: Pubmed search. Results: Deep learning has demonstrated effectiveness in analyzing structural OCT images in patients with neovascular AMD. This review outlines the role of deep learning in identifying and measuring biomarkers linked to an elevated risk of transitioning to the neovascular form of AMD. Additionally, deep learning techniques can quantify critical OCT features associated with neovascular AMD, which have prognostic implications for these patients. Incorporating deep learning into the assessment of neovascular AMD eyes holds promise for enhancing clinical management strategies for affected individuals. Conclusion: Several studies have demonstrated effectiveness of deep learning in assessing neovascular AMD patients and this has a promising role in the assessment of these patients.},
}
@article {pmid38929562,
year = {2024},
author = {Ong, J and Zarnegar, A and Selvam, A and Driban, M and Chhablani, J},
title = {The Complement System as a Therapeutic Target in Retinal Disease.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {6},
pages = {},
pmid = {38929562},
issn = {1648-9144},
mesh = {Humans ; *Retinal Diseases/drug therapy/physiopathology/immunology ; *Complement System Proteins/physiology ; Animals ; Complement Inactivating Agents/therapeutic use/pharmacology ; Diabetic Retinopathy/drug therapy/physiopathology ; Retina/drug effects/immunology ; },
abstract = {The complement cascade is a vital system in the human body's defense against pathogens. During the natural aging process, it has been observed that this system is imperative for ensuring the integrity and homeostasis of the retina. While this system is critical for proper host defense and retinal integrity, it has also been found that dysregulation of this system may lead to certain retinal pathologies, including geographic atrophy and diabetic retinopathy. Targeting components of the complement system for retinal diseases has been an area of interest, and in vivo, ex vivo, and clinical trials have been conducted in this area. Following clinical trials, medications targeting the complement system for retinal disease have also become available. In this manuscript, we discuss the pathophysiology of complement dysfunction in the retina and specific pathologies. We then describe the results of cellular, animal, and clinical studies targeting the complement system for retinal diseases. We then provide an overview of complement inhibitors that have been approved by the Food and Drug Administration (FDA) for geographic atrophy. The complement system in retinal diseases continues to serve as an emerging therapeutic target, and further research in this field will provide additional insights into the mechanisms and considerations for treatment of retinal pathologies.},
}
@article {pmid38929085,
year = {2024},
author = {Ortiz, C and Tahiri, H and Yang, C and Gilbert, C and Fortin, C and Hardy, P},
title = {The microRNA Let-7f Induces Senescence and Exacerbates Oxidative Stress in Retinal Pigment Epithelial Cells.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {6},
pages = {},
pmid = {38929085},
issn = {2076-3921},
support = {Dr. Christine Corriveau Ocular Oncology Research Fund//Universit&#xe9; de Montr&#xe9;al/ ; },
abstract = {This study aims to investigate the role of microRNA let-7f in the dysfunction and degeneration of retinal pigment epithelium (RPE) cells through the induction of senescence and oxidative stress. Furthermore, we explore whether let-7f inhibition can protect these cells against sodium iodate (SI)-induced oxidative stress. Oxidative stress and let-7f expression are reciprocally regulated in retinal pigment epithelial cells. Overexpression of let-7f in ARPE-19 cells induced oxidative stress as demonstrated by increased reactive oxygen species (ROS) production as well as senescence. Inhibition of let-7f successfully protected RPE cells from the detrimental effects induced by SI. In addition, let-7f overexpression induced RPE cellular dysfunction by diminishing their migratory capabilities and reducing the phagocytosis of porcine photoreceptor outer segments (POS). Results were further confirmed in vivo by intravitreal injections of SI and let-7f antagomir in C57BL/6 mice. Our results provide strong evidence that let-7f is implicated in the dysfunction of RPE cells through the induction of senescence and oxidative injury. These findings may help to uncover novel and relevant processes in the pathogenesis of dry AMD.},
}
@article {pmid38928273,
year = {2024},
author = {Brodzka, S and Baszyński, J and Rektor, K and Hołderna-Bona, K and Stanek, E and Kurhaluk, N and Tkaczenko, H and Malukiewicz, G and Woźniak, A and Kamiński, P},
title = {Immunogenetic and Environmental Factors in Age-Related Macular Disease.},
journal = {International journal of molecular sciences},
volume = {25},
number = {12},
pages = {},
pmid = {38928273},
issn = {1422-0067},
mesh = {Humans ; *Macular Degeneration/genetics/etiology ; Risk Factors ; Genetic Predisposition to Disease ; Metals, Heavy/toxicity/adverse effects ; Environmental Exposure/adverse effects ; Immunogenetics ; },
abstract = {Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment.},
}
@article {pmid38928111,
year = {2024},
author = {Bergandi, L and Palladino, G and Meduri, A and De Luca, L and Silvagno, F},
title = {Vitamin D and Sulforaphane Decrease Inflammatory Oxidative Stress and Restore the Markers of Epithelial Integrity in an In Vitro Model of Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {25},
number = {12},
pages = {},
pmid = {38928111},
issn = {1422-0067},
mesh = {Humans ; *Macular Degeneration/metabolism/drug therapy/pathology ; *Isothiocyanates/pharmacology ; *Oxidative Stress/drug effects ; *Sulfoxides/pharmacology ; *Vitamin D/pharmacology ; *Reactive Oxygen Species/metabolism ; Cell Line ; Vascular Endothelial Growth Factor A/metabolism ; Inflammation/metabolism/drug therapy/pathology ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Epithelial Cells/metabolism/drug effects ; Transforming Growth Factor beta/metabolism ; Biomarkers/metabolism ; Interleukin-8/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is strictly linked to chronic oxidative stress, inflammation, loss of epithelial barrier integrity, and often with abnormal new blood vessel development. In this study, the retinal epithelial cell line ARPE-19 was treated with pro-inflammatory transforming growth factor-beta (TGF-β) to investigate the activity of vitamin D (VD) and sulforaphane (SF) in abating the consequences of oxidative stress and inflammation. The administration of VD and SF lowered reactive oxygen species (ROS) levels, and abated the related expression of the pro-inflammatory cytokines interleukin-6 and interleukin-8 induced by TGF-β. We evaluated mitochondrial respiration as a source of ROS production, and we discovered that the increased transcription of respiratory elements triggered by TGF-β was prevented by VD and SF. In this model of inflamed epithelium, the treatment with VD and SF also reduced the secretion of VEGF, a key angiogenic factor, and restored the markers of epithelial integrity. Remarkably, all the observed biological effects were potentiated by the co-stimulation with the two compounds and were not mediated by VD receptor expression but rather by the ERK 1/2 pathway. Altogether, the results of this study reveal the powerful synergistic anti-inflammatory activity of SF and VD and lay the foundation for future clinical assessment of their efficacy in AMD.},
}
@article {pmid38927804,
year = {2024},
author = {Lee, KG and Song, SJ and Lee, S and Kim, BH and Kong, M and Lee, KM},
title = {FQ-UWF: Unpaired Generative Image Enhancement for Fundus Quality Ultra-Widefield Retinal Images.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {6},
pages = {},
pmid = {38927804},
issn = {2306-5354},
abstract = {Ultra-widefield (UWF) retinal imaging stands as a pivotal modality for detecting major eye diseases such as diabetic retinopathy and retinal detachment. However, UWF exhibits a well-documented limitation in terms of low resolution and artifacts in the macular area, thereby constraining its clinical diagnostic accuracy, particularly for macular diseases like age-related macular degeneration. Conventional supervised super-resolution techniques aim to address this limitation by enhancing the resolution of the macular region through the utilization of meticulously paired and aligned fundus image ground truths. However, obtaining such refined paired ground truths is a formidable challenge. To tackle this issue, we propose an unpaired, degradation-aware, super-resolution technique for enhancing UWF retinal images. Our approach leverages recent advancements in deep learning: specifically, by employing generative adversarial networks and attention mechanisms. Notably, our method excels at enhancing and super-resolving UWF images without relying on paired, clean ground truths. Through extensive experimentation and evaluation, we demonstrate that our approach not only produces visually pleasing results but also establishes state-of-the-art performance in enhancing and super-resolving UWF retinal images. We anticipate that our method will contribute to improving the accuracy of clinical assessments and treatments, ultimately leading to better patient outcomes.},
}
@article {pmid38927656,
year = {2024},
author = {Rowe, LW and Ciulla, TA},
title = {Gene Therapy for Non-Hereditary Retinal Disease: Age-Related Macular Degeneration, Diabetic Retinopathy, and Beyond.},
journal = {Genes},
volume = {15},
number = {6},
pages = {},
pmid = {38927656},
issn = {2073-4425},
mesh = {Humans ; *Diabetic Retinopathy/therapy/genetics ; *Genetic Therapy/methods ; *Macular Degeneration/therapy/genetics ; Genetic Vectors/genetics ; Dependovirus/genetics ; Vascular Endothelial Growth Factor A/genetics ; Animals ; },
abstract = {Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. This manuscript reviews ongoing gene therapy clinical trials for these disorders, including ABBV-RGX-314, ixoberogene soroparvovec (ixo-vec), and 4D-150. ABBV-RGX-314 utilizes an adeno-associated virus (AAV) vector to deliver a transgene encoding a ranibizumab-like anti-VEGF antibody fragment, demonstrating promising results in Phase 1/2a and ongoing Phase 2b/3 trials. Ixo-vec employs an AAV2.7m8 capsid for intravitreal delivery of a transgene expressing aflibercept, showing encouraging outcomes in Phase 1 and ongoing Phase 2 trials. 4D-150 utilizes an evolved vector to express both aflibercept and a VEGF-C inhibitory RNAi, exhibiting positive interim results in Phase 1/2 studies. Other therapies reviewed include EXG102-031, FT-003, KH631, OLX10212, JNJ-1887, 4D-175, and OCU410. These therapies offer potential advantages of reduced treatment frequency and enhanced safety profiles, representing a paradigm shift in management towards durable and efficacious cellular-based biofactories. These advancements in gene therapy hold promise for improving outcomes in AMD and addressing the complex challenges of DME and DR, providing new avenues for the treatment of diabetic eye diseases.},
}
@article {pmid38927058,
year = {2024},
author = {Xu, Y and Tummala, SR and Chen, X and Vardi, N},
title = {VDAC in Retinal Health and Disease.},
journal = {Biomolecules},
volume = {14},
number = {6},
pages = {},
pmid = {38927058},
issn = {2218-273X},
support = {2023A1515012397//National Science Foundation of Guangdong Province/ ; },
mesh = {Humans ; *Voltage-Dependent Anion Channels/metabolism ; *Retina/metabolism ; Animals ; Oxidative Stress ; Retinal Diseases/metabolism/pathology ; Mitochondria/metabolism ; Retinitis Pigmentosa/metabolism/pathology ; },
abstract = {The retina, a tissue of the central nervous system, is vital for vision as its photoreceptors capture light and transform it into electrical signals, which are further processed before they are sent to the brain to be interpreted as images. The retina is unique in that it is continuously exposed to light and has the highest metabolic rate and demand for energy amongst all the tissues in the body. Consequently, the retina is very susceptible to oxidative stress. VDAC, a pore in the outer membrane of mitochondria, shuttles metabolites between mitochondria and the cytosol and normally protects cells from oxidative damage, but when a cell's integrity is greatly compromised it initiates cell death. There are three isoforms of VDAC, and existing evidence indicates that all three are expressed in the retina. However, their precise localization and function in each cell type is unknown. It appears that most retinal cells express substantial amounts of VDAC2 and VDAC3, presumably to protect them from oxidative stress. Photoreceptors express VDAC2, HK2, and PKM2-key proteins in the Warburg pathway that also protect these cells. Consistent with its role in initiating cell death, VDAC is overexpressed in the retinal degenerative diseases retinitis pigmentosa, age related macular degeneration (AMD), and glaucoma. Treatment with antioxidants or inhibiting VDAC oligomerization reduced its expression and improved cell survival. Thus, VDAC may be a promising therapeutic candidate for the treatment of these diseases.},
}
@article {pmid38926553,
year = {2024},
author = {Kang, SW and Choi, J and Sheth, VS and Nowosielska, A and Misiuk-Hojlo, M and Papp, A and Brown, DM and Lee, JH and Barak, Y},
title = {Comparison of the efficacy and safety of SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14752},
pmid = {38926553},
issn = {2045-2322},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Recombinant Fusion Proteins/adverse effects/therapeutic use/administration &amp; dosage ; Male ; Female ; Aged ; *Visual Acuity/drug effects ; *Intravitreal Injections ; Treatment Outcome ; Macular Degeneration/drug therapy ; Middle Aged ; Double-Blind Method ; Aged, 80 and over ; Choroidal Neovascularization/drug therapy ; Biosimilar Pharmaceuticals/therapeutic use/adverse effects/administration &amp; dosage ; Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; },
abstract = {To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.},
}
@article {pmid38926484,
year = {2024},
author = {Tseng, YT and Huang, ST and Wang, CH and Wang, LY and Kuo, YC},
title = {Association of smoking cessation patterns and untreated smoking with glaucoma, cataract, and macular degeneration: a population-based retrospective study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14788},
pmid = {38926484},
issn = {2045-2322},
support = {RD-111-03//Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Taiwan/ ; },
mesh = {Humans ; Male ; Female ; *Smoking Cessation ; *Glaucoma/epidemiology/etiology ; Middle Aged ; *Macular Degeneration/epidemiology/etiology ; Retrospective Studies ; *Cataract/epidemiology ; Taiwan/epidemiology ; Aged ; Adult ; Smoking/adverse effects/epidemiology ; Tobacco Use Cessation Devices ; Incidence ; Varenicline/therapeutic use ; },
abstract = {This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13-0.87, P = 0.024). When stratified by dose, short-term NRT use (8-28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16-0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36-1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.},
}
@article {pmid38925903,
year = {2025},
author = {Berhuni, M and Tıskaoğlu, NS and Ozturkmen, C},
title = {Lack of Response to Intravitreal Ranibizumab Treatment in Adult Onset Foveomacular Vitelliform Dystrophy Complicated with Choroidal Neovascularization: A Case Report.},
journal = {Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti},
volume = {81},
number = {1},
pages = {38-40},
doi = {10.31348/2024/21},
pmid = {38925903},
issn = {1211-9059},
mesh = {Humans ; *Ranibizumab/administration &amp; dosage ; Female ; *Vitelliform Macular Dystrophy/drug therapy/diagnostic imaging/diagnosis ; Middle Aged ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage ; Choroidal Neovascularization/drug therapy/diagnostic imaging ; Antibodies, Monoclonal, Humanized/administration &amp; dosage ; },
abstract = {Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare disease characterized by accumulation of yellowish deposits in the macula. Rarely, it may be complicated by choroidal neovascularization (CNV). Cases with CNV may be confused with occult CNV in age-related macular degeneration. In our case, we will present the visual and anatomical results of a patient with AOVF-related CNV, in which we administered 3 doses of intravitreal ranibizumab (IVR). A 59-year-old female patient, who attended our clinic with the complaint of decreased vision in both eyes, was diagnosed with AOVF-related CNV in both eyes and was treated with 3 doses of IVR for 3 months. Despite the improvement in visual and anatomical functions 1 month after the first dose, vision decreased, and anatomical functions regressed to the pre-injection state in continued injections. IVR therapy is not an appropriate treatment option in the treatment of AOVF-associated CNV.},
}
@article {pmid38925899,
year = {2024},
author = {Fellner, Z and Majtánová, N and Kolář, P and Krišková, P and Kéri, P},
title = {Treatment Regimens of Neovascular Form of Age-Related Macular Degeneration. A Review.},
journal = {Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti},
volume = {80},
number = {6},
pages = {287-293},
doi = {10.31348/2024/25},
pmid = {38925899},
issn = {1211-9059},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Macular Degeneration/drug therapy/diagnosis/physiopathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Bevacizumab/administration &amp; dosage/therapeutic use ; },
abstract = {This article presents an overview of treatment regimens of drugs containing antivascular endothelial growth factor for the treatment of neovascular form of age-related macular degeneration. Currently, drugs containing antivascular endothelial growth factor are the only effective treatment for this chronic and progressive disease. The treatment regimens for this disease in the last two decades have seen a shift from a simple endeavor to stabilize the disease to achieving maximum improvement of visual acuity and its maintenance, with improvement of the patient's quality of life and a minimal treatment burden on patients and their families. Other goals of the alternative dosing regimens that have replaced the original fixed regimens were greater individualization of the dosing regimen, better patient cooperation, saving financial costs and reducing the burden on application centers. Age-related macular degeneration, whether dry form or wet form, represents a serious health and socioeconomic problem, as the disease is one of the most common causes of severe and irreversible central visual acuity disorders up to the degree of practical blindness of one or both eyes in people over 50 years of age in developed industrialized countries. The most important issue is to ensure early diagnosis of this disease, followed by prompt and continuous treatment with an individualized proactive treatment regimen, with the aim of stabilizing and improving anatomical and functional results.},
}
@article {pmid38922557,
year = {2024},
author = {Gregg, AT and Wang, T and Szczepan, M and Lam, E and Yagi, H and Neilsen, K and Wang, X and Smith, LEH and Sun, Y},
title = {Botulinum neurotoxin serotype A inhibited ocular angiogenesis through modulating glial activation via SOCS3.},
journal = {Angiogenesis},
volume = {27},
number = {4},
pages = {753-764},
pmid = {38922557},
issn = {1573-7209},
support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01 EY017017/EY/NEI NIH HHS/United States ; P50 HD105351/HD/NICHD NIH HHS/United States ; R01EY030140, R01EY029238//NIH/NEI/ ; R01 EY030140/EY/NEI NIH HHS/United States ; U54 HD090255/HD/NICHD NIH HHS/United States ; R01 EY030904/EY/NEI NIH HHS/United States ; R01EY017017, R01EY030904, 1U54HD090255//NIH/NEI/ ; },
mesh = {Animals ; *Suppressor of Cytokine Signaling 3 Protein/metabolism/genetics ; *Neuroglia/metabolism/drug effects/pathology ; *Botulinum Toxins, Type A/pharmacology ; *Choroidal Neovascularization/pathology/metabolism/drug therapy ; Mice ; Mice, Inbred C57BL ; Vascular Endothelial Growth Factor A/metabolism/genetics ; Mice, Knockout ; Suppressor of Cytokine Signaling Proteins/metabolism/genetics ; Angiogenesis ; },
abstract = {BACKGROUND: Pathological angiogenesis causes significant vision loss in neovascular age-related macular degeneration and other retinopathies with neovascularization (NV). Neuronal/glial-vascular interactions influence the release of angiogenic and neurotrophic factors. We hypothesized that botulinum neurotoxin serotype A (BoNT/A) modulates pathological endothelial cell proliferation through glial cell activation and growth factor release.<br><br>METHODS: A laser-induced choroidal NV (CNV) was employed to investigate the anti-angiogenic effects of BoNT/A. Fundus fluorescence angiography, immunohistochemistry, and real-time PCR were used to assess BoNT/A efficacy in inhibiting CNV and the molecular mechanisms underlying this inhibition. Neuronal and glial suppressor of cytokine signaling 3 (SOCS3) deficient mice were used to investigate the molecular mechanisms of BoNT/A in inhibiting CNV via SOCS3.<br><br>FINDINGS: In laser-induced CNV mice with intravitreal BoNT/A treatment, CNV lesions decreased&#x2009;>&#x2009;30%; vascular leakage and retinal glial activation were suppressed; and Socs3 mRNA expression was induced while vascular endothelial growth factor A (Vegfa) mRNA expression was suppressed. The protective effects of BoNT/A on CNV development were diminished in mice lacking neuronal/glial SOCS3.<br><br>CONCLUSION: BoNT/A suppressed laser-induced CNV and glial cell activation, in part through SOCS3 induction in neuronal/glial cells. BoNT/A treatment led to a decrease of pro-angiogenic factors, including VEGFA, highlighting the potential of BoNT/A as a therapeutic intervention for pathological angiogenesis in retinopathies.},
}
@article {pmid38918699,
year = {2024},
author = {Jingzhi, W and Cui, X},
title = {The Impact of Blood and Urine Biomarkers on Age-Related Macular Degeneration: Insights from Mendelian Randomization and Cross-sectional Study from NHANES.},
journal = {Biological procedures online},
volume = {26},
number = {1},
pages = {19},
pmid = {38918699},
issn = {1480-9222},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of blindness, affecting millions worldwide. Its complex pathogenesis involves a variety of risk factors, including lipid metabolism and inflammation. This study aims to elucidate the causal relationships between biomarkers related to these processes and AMD, leveraging Mendelian randomization (MR) and cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES).<br><br>METHOD: We conducted a two-phase study, initially using MR to explore the causality between 35 biomarkers and various AMD subtypes, followed by observational analysis with NHANES data to validate these findings.<br><br>RESULTS: MR analysis identified a protective role of TG and a risk factor role of HDL-C and CRP in AMD development. NHANES data corroborated these findings, highlighting a nuanced relationship between these biomarkers and AMD. Notably, lipid metabolism-related biomarkers showed stronger associations with early AMD, whereas CRP's significance was pronounced in late AMD.<br><br>CONCLUSION: This comprehensive analysis, combining MR with NHANES data, reinforces the importance of lipid metabolism and inflammation in AMD's etiology. Future research should further investigate these biomarkers' mechanisms and their potential as therapeutic targets for AMD prevention and treatment.},
}
@article {pmid38917394,
year = {2024},
author = {DeBoer, CMT and Rasmussen, DK and Franco, JA and Mahajan, VB},
title = {Emerging Oral Pharmaceuticals for Dry Age-Related Macular Degeneration: Mechanism of Action, Current Clinical Status, and Future Directions.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {9},
pages = {528-534},
doi = {10.3928/23258160-20240430-02},
pmid = {38917394},
issn = {2325-8179},
mesh = {Humans ; Administration, Oral ; *Geographic Atrophy/drug therapy ; },
abstract = {Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there has been a flurry of research focused on discovering new targets to prevent worsening of dry AMD. In 2023, the US Food and Drug Administration approved the first two intravitreal complement inhibitors to slow the rate of geographic atrophy progression. However, serial intravitreal injections for a chronic progressive disease are burdensome for patients and have procedural risks. Therefore, there is significant research to discover novel oral medications to manage dry AMD. Several oral medications are currently in phase 2 and 3 clinical trials for dry AMD, whereas others have had recent readouts on their clinical trials and efficacy. The purpose of this review is to describe the therapeutic pathways currently being investigated and to provide an update on the clinical status of novel oral medications for the management of dry AMD. [Ophthalmic Surg Lasers Imaging Retina 2024;55:528-534.].},
}
@article {pmid38915383,
year = {2024},
author = {Dou, R and Jiang, J},
title = {Efficacy and safety of Brolucizumab for neovascular age-related macular degeneration: a systematic review and meta-analysis.},
journal = {PeerJ},
volume = {12},
number = {},
pages = {e17561},
pmid = {38915383},
issn = {2167-8359},
mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Treatment Outcome ; Visual Acuity/drug effects ; Wet Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis.<br><br>MATERIALS AND METHODS: Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with &#x2265;1 serious adverse events, and participants with &#x2265;1 adverse events were analyzed.<br><br>RESULTS: Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = -0.65, 95% CI [-0.17 to -0.23], P < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56-0.79], P < 0.05], and the safety of participants with &#x2265;1 serious adverse events [RR = 0.57, 95% CI [0.39-0.84], P < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = -1.16, 95% CI [-2.79 to 0.47], P > 0.05] or the safety of participants with &#x2265;1 adverse events [RR = 1.07, 95% CI [0.97-1.17], P > 0.05].<br><br>CONCLUSIONS: Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with &#x2265;1 serious adverse events.},
}
@article {pmid38914302,
year = {2024},
author = {Salzman, MM and Takimoto, T and Foster, ML and Mowat, FM},
title = {Differential gene expression between central and peripheral retinal regions in dogs and comparison with humans.},
journal = {Experimental eye research},
volume = {245},
number = {},
pages = {109980},
pmid = {38914302},
issn = {1096-0007},
support = {K08 EY028628/EY/NEI NIH HHS/United States ; P30 ES025128/ES/NIEHS NIH HHS/United States ; },
mesh = {Dogs ; Animals ; Humans ; *Retina/metabolism ; Gene Expression Regulation/physiology ; Gene Expression Profiling ; Disease Models, Animal ; Transcriptome ; Retinal Pigment Epithelium/metabolism ; Eye Proteins/genetics/metabolism ; Retinal Diseases/genetics/metabolism ; Male ; Female ; Choroid/metabolism ; },
abstract = {The dog retina contains a central macula-like region, and there are reports of central retinal disorders in dogs with shared genetic etiologies with humans. Defining central/peripheral gene expression profiles may provide insight into the suitability of dogs as models for human disorders. We determined central/peripheral posterior eye gene expression profiles in dogs and interrogated inherited retinal and macular disease-associated genes for differential expression between central and peripheral regions. Bulk tissue RNA sequencing was performed on 8 mm samples of the dog central and superior peripheral regions, sampling retina and retinal pigmented epithelium/choroid separately. Reads were mapped to CanFam3.1, read counts were analyzed to determine significantly differentially expressed genes (DEGs). A similar analytic pipeline was used with a published bulk-tissue RNA sequencing human dataset. Pathways and processes involved in significantly DEGs were identified (Database for Annotation, Visualization and Integrated Discovery). Dogs and humans shared the extent and direction of central retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. Many genes implicated in heritable retinal disorders in dogs and humans were differentially expressed between central and periphery. Approximately half of genes associated with human age-related macular degeneration were differentially expressed in human and dog tissues. We have identified similarities and differences in central/peripheral gene expression profiles between dogs and humans which can be applied to further define the relevance of dogs as models for human retinal disorders.},
}
@article {pmid38914301,
year = {2024},
author = {Preya, UH and Sayed, S and Nguyen, NL and Kim, JT},
title = {Potential role of CTSS in AMDImmune modulatory and anti-angiogenic effects of cathepsin S knockdown in ARPE-19 cells.},
journal = {Experimental eye research},
volume = {245},
number = {},
pages = {109981},
doi = {10.1016/j.exer.2024.109981},
pmid = {38914301},
issn = {1096-0007},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Animals ; Mice ; *Choroidal Neovascularization/metabolism/genetics/pathology ; *Oxidative Stress ; *Cathepsins/metabolism/genetics ; *Macular Degeneration/metabolism/genetics/pathology ; *Disease Models, Animal ; Mice, Inbred C57BL ; Blotting, Western ; Cell Line ; Cytokines/metabolism ; RNA, Small Interfering/genetics ; Human Umbilical Vein Endothelial Cells/metabolism ; },
abstract = {We aimed to determine the role of cathepsin S (CTSS) in modulating oxidative stress-induced immune and inflammatory reactions and angiogenesis in age-related macular degeneration. Human retinal pigment epithelium cells line ARPE-19 (immature) were maintained and treated with H2O2. The expression of CTSS, inflammatory cytokines, and complement factors induced by oxidative stress was compared between cells incubated without (control) and with CTSS knockdown (using small interfering ribonucleic acid; siRNA). To evaluate the role of CTSS in angiogenesis, we assayed tube formation using human umbilical vein endothelial cells and conditioned medium from ARPE-19 cells. We also used a mouse model of laser-induced choroidal neovascularization. CTSS levels were higher in ARPE-19 cells treated with H2O2 than in control cells. Oxidative stress-induced CTSS resulted in significantly elevated transcription of nuclear factor kappa B-dependent inflammatory cytokines, complement factors C3a and C5a, membrane attack complex (C5b-9), and C3a and C5a receptors. siRNA-mediated knockdown of CTSS reduced the number of inflammatory signals. Furthermore, oxidative stress-induced CTSS regulated the expression of peroxisome proliferator-activated receptor γ and vascular endothelial growth factor A/Akt serine/threonine kinase family signaling, which led to angiogenesis. Tube formation assays and mouse models of choroidal neovascularization revealed that CTSS knockdown ameliorated angiogenesis in vitro and in vivo. The present findings suggest that CTSS modulates the complement pathway, inflammatory reactions, and neovascularization, and that CTSS knockdown induces potent immunomodulatory effects. Hence, it could be a promising target for the prevention and treatment of early- and late-stage age-related macular degeneration.},
}
@article {pmid38914294,
year = {2024},
author = {Nielsen, JS and Chang, A and Holekamp, NM and Cavichini-Cordeiro, M and Lin, SL and Heinrich, D and Maass, KF and Menezes, A and Singh, N and Pieramici, DJ},
title = {Supplemental Intravitreal Ranibizumab Injections in Eyes Treated with the Port Delivery System with Ranibizumab in the Archway Trial.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {12},
pages = {1127-1139},
doi = {10.1016/j.oret.2024.06.012},
pmid = {38914294},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; Dose-Response Relationship, Drug ; Drug Delivery Systems ; Fluorescein Angiography/methods ; Follow-Up Studies ; *Intravitreal Injections ; *Ranibizumab/administration &amp; dosage ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {PURPOSE: To determine the proportion and characteristics of eyes with neovascular age-related macular degeneration (nAMD) treated with the Port Delivery System (PDS) with ranibizumab that receive supplemental intravitreal ranibizumab injections because of changes in best-corrected visual acuity (BCVA) or central subfield thickness (CST), or both, and to investigate the safety and efficacy of supplemental injections in eyes with the PDS.<br><br>DESIGN: Post hoc analyses of data from the phase III, randomized, multicenter, open-label, active-comparator Archway trial (NCT03677934).<br><br>PARTICIPANTS: Adults with nAMD diagnosed within 9 months of screening previously responsive to anti-VEGF therapy.<br><br>INTERVENTION: Four hundred eighteen patients were randomized to the PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (Q24W) or monthly intravitreal ranibizumab 0.5 mg for 96 weeks.<br><br>RESULTS: Of the 246 eyes treated with the PDS Q24W and assessed for supplemental treatment criteria, the vast majority (94.6%-98.4%) did not receive supplemental treatment during each retreatment interval, with 87.4% not receiving supplemental treatment at any point during the trial. Of the 31 eyes receiving supplemental treatment, 58.1% received 1 injection and 32.3% received 2. At baseline, eyes receiving supplemental treatment were significantly more likely to have thicker retinas (mean CST, 370.5&#x3bc;m vs. 304.4&#x3bc;m; P&#xa0;= 0.0001), subretinal fluid (54.8% vs. 21.2%; P < 0.0001), and larger pigment epithelial detachment height (215.7 &#x3bc;m vs. 175.9 &#x3bc;m; P&#xa0;=&#xa0;0.003). These features have previously been associated with difficult-to-treat nAMD. Although BCVA and CST generally remained constant throughout the trial in eyes without supplemental treatment, the small number of eyes receiving supplemental treatment on average lost 1 line of vision from baseline to week 96 (mean,&#xa0;-5.7 ETDRS score letters) and CST continued to increase over time. Absolute BCVA at week 96 was similar irrespective of supplemental treatment status (71.1 and 73.7 letters). Best-corrected visual acuity and CST generally improved within 28 days of supplemental treatment.<br><br>CONCLUSIONS: Although the PDS Q24W effectively maintains vision and retinal stability in most eyes with nAMD, a small proportion of patients with features of difficult-to-treat nAMD may benefit from supplemental intravitreal anti-VEGF injections and initial close monitoring is recommended.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38914153,
year = {2024},
author = {Pu, J and Zhuang, X and Li, M and Zhang, X and Su, Y and He, G and Hao, X and Wen, F},
title = {Analyzing Formation and Absorption of Avascular Subretinal Hyperreflective Material in nAMD From OCTA-Based Insights.},
journal = {American journal of ophthalmology},
volume = {267},
number = {},
pages = {192-203},
doi = {10.1016/j.ajo.2024.06.019},
pmid = {38914153},
issn = {1879-1891},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Prospective Studies ; Aged ; *Fluorescein Angiography/methods ; *Retinal Vessels/diagnostic imaging ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Angiogenesis Inhibitors/therapeutic use/pharmacokinetics ; *Visual Acuity/physiology ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Follow-Up Studies ; Intravitreal Injections ; Middle Aged ; Fundus Oculi ; },
abstract = {PURPOSE: To investigate the formation and absorption of avascular subretinal hyperreflective material (avSHRM) in neovascular age-related macular degeneration (nAMD) based on optical coherence tomography angiography (OCTA) characteristics.<br><br>DESIGN: Prospective cohort study.<br><br>METHODS: This study included patients with treatment-naive nAMD who were followed up for 3 months. Subjects were classified into an avSHRM group and a non-avSHRM group based on the presence of avSHRM at baseline. Quantitative OCTA characteristics including explant area, perimeter, vessel area, density, length, junctions, endpoints, lacunarity, maximum vessel caliber, vessel dispersion, and fractal dimension were assessed, and 3-dimensional volume and optical density ratio (ODR) of avSHRM were measured. Comparison analyses, correlation coefficients, and regression models were applied to explore factors associated with avSHRM formation and absorption.<br><br>RESULTS: A total of 88 eyes from 88 patients (39 female) were enrolled. Compared to the non-avSHRM group, the avSHRM group exhibited a more intricate vasculature, characterized by higher values of macular neovascularization (MNV) perimeter, vessel area, total vessel length, total number of junctions, and total number of endpoints (all P < .05), as well as the maximum vessel caliber (P < .001). In the multivariate model, which was adjusted for age, sex, and types of medications, avSHRM absorption was correlated with baseline average vessel length, maximum vessel caliber, and avSHRM ODR (standardized &#x3b2; = 0.274, -0.367, and -0.334; P = .049, .010, and .018, respectively), with an adjusted R&#xb2; of 0.453.<br><br>CONCLUSIONS: Quantitative OCTA measurements can be used for assessing the dynamics of avSHRM in nAMD. Patients with more complex vasculature are at higher risk for avSHRM formation. Average vessel length, maximum vessel diameter, and avSHRM ODR play a role in its absorption.},
}
@article {pmid38913934,
year = {2024},
author = {Shanidze, NM and Verghese, P},
title = {Smooth pursuit deficits impact dynamic visual acuity in macular degeneration.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {101},
number = {6},
pages = {435-442},
pmid = {38913934},
issn = {1538-9235},
support = {90REGE0018/ACL/ACL HHS/United States ; R00 EY026994/EY/NEI NIH HHS/United States ; R01 EY027390/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Visual Acuity/physiology ; *Macular Degeneration/physiopathology ; *Pursuit, Smooth/physiology ; Aged ; Male ; Female ; Middle Aged ; Aged, 80 and over ; Ophthalmoscopy ; },
abstract = {SIGNIFICANCE: Prior studies with large, highly visible targets report low smooth pursuit gains in individuals with macular degeneration (MD). We show that lower gains persist even when observers are pursuing a target that requires discrimination at the acuity limit. This low gain causes retinal slip, potentially leading to motion blur and target disappearance in the scotoma, which further compromise the visibility of moving object.<br><br>PURPOSE: In this study, we examine whether the characteristics of smooth pursuit (pursuit gain and placement of the fixational locus relative to the target) change when the task requires dynamic visual acuity.<br><br>METHODS: Using the scanning laser ophthalmoscope, we recorded smooth pursuit eye movements in 10 eyes of 6 MD participants and 7 eyes of 4 age-matched controls in response to leftward- or rightward-moving annular targets (O) that briefly (300 milliseconds) changed to a Landolt C at one of several time points during the pursuit trial. Participants were asked to pursue the target and indicate the direction of the C opening.<br><br>RESULTS: Individuals with MD had lower pursuit gains and fewer saccades during the C presentation than during the O, compared with their age-matched peers. Further, pursuit gain, but not the distance of the retinal pursuit locus from the target, predicted task performance in the MD group.<br><br>CONCLUSIONS: Our findings suggest that compromised pursuit gain in MD participants likely further compromises their dynamic visual acuity and thus ability to view moving targets.},
}
@article {pmid38913289,
year = {2024},
author = {Grzybowski, A and Jin, K and Zhou, J and Pan, X and Wang, M and Ye, J and Wong, TY},
title = {Retina Fundus Photograph-Based Artificial Intelligence Algorithms in Medicine: A Systematic Review.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {8},
pages = {2125-2149},
pmid = {38913289},
issn = {2193-8245},
abstract = {We conducted a systematic review of research in artificial intelligence (AI) for retinal fundus photographic images. We highlighted the use of various AI algorithms, including deep learning (DL) models, for application in ophthalmic and non-ophthalmic (i.e., systemic) disorders. We found that the use of AI algorithms for the interpretation of retinal images, compared to clinical data and physician experts, represents an innovative solution with demonstrated superior accuracy in identifying many ophthalmic (e.g., diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve disorders), and non-ophthalmic disorders (e.g., dementia, cardiovascular disease). There has been a significant amount of clinical and imaging data for this research, leading to the potential incorporation of AI and DL for automated analysis. AI has the potential to transform healthcare by improving accuracy, speed, and workflow, lowering cost, increasing access, reducing mistakes, and transforming healthcare worker education and training.},
}
@article {pmid38913217,
year = {2024},
author = {Sariyeva Ismayilov, A and Duru, Y and Çağlar, T and Erseven, C and Ulusoy, MO},
title = {Predictive factors of age-related macular degeneration with poor response to three loading doses of anti-vascular endothelial growth factor.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {264},
pmid = {38913217},
issn = {1573-2630},
mesh = {Humans ; Retrospective Studies ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Female ; *Intravitreal Injections ; *Tomography, Optical Coherence/methods ; *Bevacizumab/administration &amp; dosage ; Aged ; *Fluorescein Angiography/methods ; *Visual Acuity ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Fundus Oculi ; Aged, 80 and over ; Macula Lutea/pathology/diagnostic imaging ; Follow-Up Studies ; Middle Aged ; },
abstract = {PURPOSE: To evaluate the predictive factors of neovascular age-related macular degeneration (nAMD) with poor response to three loading doses of intravitreal bevacizumab (IVB).<br><br>METHODS: A retrospective cohort study was performed on nAMD patients three loading IVB initial treatment. The patients were divided into two groups, without residual fluid on optical coherence tomography (OCT) images (Group 1) and with residual fluid (Group 2). Demographic data, OCT findings, and morphological features of macular neovascularization (MNV) in optical coherence tomography angiography (OCTA) were recorded.<br><br>RESULTS: The study included one hundred thirty-six eyes of 120 patients (Group 1: n&#x2009;=&#x2009;66 eyes, Group 2: n&#x2009;=&#x2009;70 eyes). Central macular thickness, presence of intraretinal fluid, subretinal fluid, hyperreflective foci-band, pigment epithelial detachment (PED), and prechoroidal cleft were similar between the two groups. Pre-injection central choroidal thickness (CCT) was 214.17&#x2009;&#xb1;&#x2009;50.28&#xa0;&#xb5;m in Group 1 and 247.40&#x2009;&#xb1;&#x2009;60.55&#xa0;&#xb5;m in Group 2 (p&#x2009;=&#x2009;0.021). PED width (p&#x2009;=&#x2009;0.028) and PED area (p&#x2009;=&#x2009;0.042) were statistically significantly higher in Group 1. When the morphology of MNV in OCTA was examined, branching (p&#x2009;=&#x2009;0.736), loops (p&#x2009;=&#x2009;0.442), peripheral arcade (p&#x2009;=&#x2009;0.600), hypointense halo (p&#x2009;=&#x2009;0.779), sea fan (p&#x2009;=&#x2009;0.250), medusa (p&#x2009;=&#x2009;0.255), pruned vascular tree pattern (p&#x2009;=&#x2009;0.148), capillary fringe (p&#x2009;=&#x2009;0.683) were similar in both groups. The presence of a closed circuit pattern was significantly higher in Group 2 (p&#x2009;=&#x2009;0.028).<br><br>CONCLUSION: Initial CCT and closed circuit pattern MNV were higher in IVB-resistant cases. It was observed that PEDs with large bases and areas responded significantly better to loading therapy. The presence of a closed-circuit pattern was an independent risk factor for poor response to loading therapy. Retrospectively registered.<br><br>REGISTRATION NUMBER: 2011-KAEK-25 2023/05-08.},
}
@article {pmid38913038,
year = {2024},
author = {Yu, H and Wu, J and Pan, G},
title = {Targeting the Ophthalmic Diseases Using Extracellular Vesicles 'Exosomes': Current Insights on Their Clinical Approval and Present Trials.},
journal = {Aging and disease},
volume = {16},
number = {3},
pages = {1225-1241},
pmid = {38913038},
issn = {2152-5250},
mesh = {Humans ; *Eye Diseases/therapy ; *Exosomes/metabolism/transplantation ; *Extracellular Vesicles/metabolism ; Animals ; Clinical Trials as Topic ; },
abstract = {Ophthalmic diseases encompass a diverse range of conditions, each necessitating tailored treatment strategies. In the realm of ophthalmic research and therapeutic interventions, various subtypes of exosomes are being explored for their regenerative, neuroprotective, and anti-inflammatory properties. Exosomes have garnered increasing attention as promising therapeutic vehicles due to their natural role in cell-to-cell communication and targeted delivery capabilities. Derived from cells, these small vesicles facilitate the transportation of numerous molecules between cells, offering advantages such as low immunogenicity, stability, and precise cell targeting. These inherent qualities make exosomes an enticing avenue for advancing treatment options for ophthalmic diseases. While ongoing research and clinical applications continue to evolve, several exosome subtypes have demonstrated potential for addressing various ophthalmic conditions, including glaucoma, age-related macular degeneration, retinal degenerative disorders, and ocular inflammatory conditions.},
}
@article {pmid38913008,
year = {2024},
author = {Titz, B and Siebourg-Polster, J and Bartolo, F and Lavergne, V and Jiang, Z and Gayan, J and Altay, L and Enders, P and Schmelzeisen, C and Ippisch, QT and Koss, MJ and Ansari-Shahrezaei, S and Garweg, JG and Fauser, S and Dieckmann, A},
title = {Implications of Ocular Confounding Factors for Aqueous Humor Proteomic and Metabolomic Analyses in Retinal Diseases.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {6},
pages = {17},
pmid = {38913008},
issn = {2164-2591},
mesh = {Humans ; *Aqueous Humor/metabolism/chemistry ; Female ; *Proteomics/methods ; Male ; Aged ; *Metabolomics ; *Eye Proteins/metabolism ; Middle Aged ; Cataract/metabolism ; Diabetic Retinopathy/metabolism ; Macular Edema/metabolism ; Wet Macular Degeneration/metabolism/diagnosis ; Aged, 80 and over ; },
abstract = {PURPOSE: To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization.<br><br>METHODS: This study recruited 138 subjects (eyes): 102 with neovascular age-related macular degeneration (nAMD), 18 with diabetic macular edema (DME), and 18 with cataract (control group). AH samples underwent analysis using Olink Target 96 proteomics and Metabolon's metabolomics platform Data analysis included correlation, differential abundance, and gene-set analysis.<br><br>RESULTS: In total, 756 proteins and 408 metabolites were quantified in AH. Total AH protein concentration was notably higher in nAMD (3.2-fold) and DME (4.1-fold) compared to controls. Pseudophakic eyes showed higher total AH protein concentrations than phakic eyes (e.g., 1.6-fold in nAMD) and a specific protein signature indicative of matrix remodeling. Unexpectedly, pupil-dilating drugs containing phenylephrine/tropicamide increased several AH proteins, notably interleukin-6 (5.4-fold in nAMD). Correcting for these factors revealed functionally relevant protein correlation clusters and disease-relevant, differentially abundant proteins across the groups. Metabolomics analysis, for which the relevance of confounder adjustment was less apparent, suggested insufficiently controlled diabetes and chronic hyperglycemia in the DME group.<br><br>CONCLUSIONS: AH protein concentration, pseudophakia, and pupil dilation with phenylephrine/tropicamide are important confounding factors for AH protein analyses. When these factors are considered, AH analyses can more clearly reveal disease-relevant factors.<br><br>TRANSLATIONAL RELEVANCE: Considering AH protein concentration, lens status, and phenylephrine/tropicamide administration as confounders is crucial for accurate interpretation of AH protein data.},
}
@article {pmid38913005,
year = {2024},
author = {Cui, K and Tang, X and Yang, B and Fan, M and Hu, A and Wu, P and Yang, F and Lin, J and Kong, H and Lu, X and Yu, S and Xu, Y and Liang, X},
title = {Sema4D Knockout Attenuates Choroidal Neovascularization by Inhibiting M2 Macrophage Polarization Via Regulation of the RhoA/ROCK Pathway.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {6},
pages = {34},
pmid = {38913005},
issn = {1552-5783},
mesh = {Animals ; Male ; Mice ; Antigens, CD/metabolism/genetics ; Blotting, Western ; *Choroidal Neovascularization/metabolism/genetics/pathology ; Disease Models, Animal ; Fluorescein Angiography ; *Macrophages/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; *rho-Associated Kinases/metabolism ; *rhoA GTP-Binding Protein/metabolism ; *Semaphorins/genetics/metabolism ; *Signal Transduction/physiology ; },
abstract = {PURPOSE: The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms.<br><br>METHODS: In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected.<br><br>RESULTS: We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice.<br><br>CONCLUSIONS: Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.},
}
@article {pmid38911030,
year = {2024},
author = {Ma, C and Li, H and Lu, S and Li, X},
title = {The Role and Therapeutic Potential of Melatonin in Degenerative Fundus Diseases: Diabetes Retinopathy and Age-Related Macular Degeneration.},
journal = {Drug design, development and therapy},
volume = {18},
number = {},
pages = {2329-2346},
pmid = {38911030},
issn = {1177-8881},
mesh = {*Melatonin/therapeutic use/pharmacology ; Humans ; *Diabetic Retinopathy/drug therapy/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Animals ; Fundus Oculi ; Antioxidants/therapeutic use/pharmacology ; },
abstract = {Degenerative fundus disease encompasses a spectrum of ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), which are major contributors to visual impairment and blindness worldwide. The development and implementation of effective strategies for managing and preventing the onset and progression of these diseases are crucial for preserving patients' visual acuity. Melatonin, a neurohormone primarily produced by the pineal gland, exhibits properties such as circadian rhythm modulation, antioxidant activity, anti-inflammatory effects, and neuroprotection within the ocular environment. Furthermore, melatonin has been shown to suppress neovascularization and reduce vascular leakage, both of which are critical in the pathogenesis of degenerative fundus lesions. Consequently, melatonin emerges as a promising therapeutic candidate for degenerative ocular diseases. This review provides a comprehensive overview of melatonin synthesis, its localization within ocular tissues, and its mechanisms of action, particularly in regulating melatonin production, thereby underscoring its potential as a therapeutic agent for degenerative fundus diseases.},
}
@article {pmid38909914,
year = {2024},
author = {Heier, JS and Cohen, MN and Chao, DL and Pepio, A and Shiraga, Y and Capuano, G and Rogers, A and Ackert, J and Sen, HN and Csaky, K},
title = {Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy Secondary to Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {131},
number = {12},
pages = {1377-1388},
doi = {10.1016/j.ophtha.2024.06.013},
pmid = {38909914},
issn = {1549-4713},
mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy/genetics ; Male ; Female ; Aged ; *Visual Acuity/physiology ; Middle Aged ; *Genetic Therapy ; *Intravitreal Injections ; *Tomography, Optical Coherence ; *Macular Degeneration/drug therapy/diagnosis ; Aged, 80 and over ; Fluorescein Angiography ; Treatment Outcome ; Phenyl Ethers ; Propanolamines ; },
abstract = {PURPOSE: To evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry age-related macular degeneration (AMD).<br><br>DESIGN: Phase 1, open-label, single-center, first-in-human clinical study.<br><br>PARTICIPANTS: Adult patients (&#x2265;50 years of age) with GA secondary to AMD in the study-treated eye (treated eye) with Snellen best-corrected visual acuity of 20/200 or worse in the treated eye (20/80 or worse after the first 3 patients), a total GA lesion size between 5 and 20 mm[2] (2-8 disc area), and best-corrected visual acuity of 20/800 or better in fellow, nontreated eye were included.<br><br>METHODS: Patients (n&#xa0;= 17) were enrolled sequentially into low-dose (3.56&#xa0;&#xd7; 10[10] viral genome/eye; n&#xa0;= 3), intermediate-dose (1.07&#xa0;&#xd7; 10[11] viral genome/eye; n&#xa0;= 3), and high-dose (3.56&#xa0;&#xd7; 10[11] viral genome/eye; n&#xa0;= 11) cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months.<br><br>MAIN OUTCOME MEASURES: Safety and tolerability outcomes included assessment of ocular and nonocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate.<br><br>RESULTS: Baseline patient characteristics were consistent with the disease under study, and all enrolled patients demonstrated foveal center-involved GA. JNJ-81201887 was well-tolerated across all cohorts, with no dose-limiting AEs. No serious or systemic AEs related to study intervention occurred. Overall, 5 of 17 patients (29%) experienced 5 events of mild ocular inflammation related to study treatment; examination findings in all resolved, and AEs resolved in 4 of 5 patients after topical steroids or observation. One unresolved vitritis event, managed with observation, occurred in a patient with an unrelated fatal AE. No endophthalmitis or new-onset choroidal neovascularization was reported. Geographic atrophy lesion growth rate was similar among all cohorts over 24 months. For treated eyes in the high-dose cohort, GA lesion growth rate showed continued decline through 24 months, with a reduction in mean square root lesion growth from 0.211 mm at months 0 through 6 to 0.056 mm at months 18 through&#xa0;24.<br><br>CONCLUSIONS: All 3 studied doses of JNJ-1887 showed a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38909889,
year = {2024},
author = {Lázaro, P and Blasco, AJ and Contreras, I and González, R and Zulueta, J and Pinilla, I},
title = {Perception of patients with retinal pathology on aspects of visual function and their management.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {99},
number = {10},
pages = {427-435},
doi = {10.1016/j.oftale.2024.06.011},
pmid = {38909889},
issn = {2173-5794},
mesh = {Humans ; *Macular Degeneration/psychology/complications ; *Diabetic Retinopathy/psychology/therapy ; Aged ; Female ; Male ; Middle Aged ; Activities of Daily Living ; Aged, 80 and over ; Surveys and Questionnaires ; Attitude to Health ; Visual Acuity ; },
abstract = {BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are highly prevalent.<br><br>OBJECTIVE: To explore perceptions of patients with AMD or DR about the impact of the disease and treatment on their daily living activities.<br><br>MATERIALS AND METHODS: Semi-structured interviews with a questionnaire developed from validated patient reported outcomes questionnaires. The questionnaire consisted of 19 questions about the disease and 9 about the treatment. The questions (items) were answered on a scale from 1 to 9. In addition, the patient interviewed was invited to make free comments on each question. Nine patients with AMD and 9 with DR were interviewed by videoconference or telephone call. A quantitative analysis of the responses and a qualitative analysis of the comments were carried out.<br><br>RESULTS: The most relevant item for patients with AMD or DR is "Recognize people when they are nearby", and "Read text in normal size font in a newspaper or book", followed, in patients with AMD, by "Do things what you would like" and, in patients with DR, "Feeling frustrated by the vision problems." Regarding the treatment, the most relevant aspects for both groups is that the treatment works and receiving appropriate information before and after the treatment. The qualitative comments were focused to the disease, the treatment, and to the role of doctors and the health system.<br><br>CONCLUSION: Quantitative responses and free comments can be useful to improve the care of patients with AMD or DR by physicians and the health system.},
}
@article {pmid38909882,
year = {2024},
author = {Pattanaik, DK and Lakshminarayanan, V and Sharma, NK and Sahu, AP},
title = {Leading edge of the a-wave of the electroretinogram and sodium iodate-induced age-related macular degeneration: A model.},
journal = {Journal of theoretical biology},
volume = {592},
number = {},
pages = {111879},
doi = {10.1016/j.jtbi.2024.111879},
pmid = {38909882},
issn = {1095-8541},
mesh = {*Iodates ; *Electroretinography ; Animals ; *Macular Degeneration/pathology/physiopathology/chemically induced ; Mice ; *Oxidative Stress/drug effects ; *Reactive Oxygen Species/metabolism ; *Retinal Cone Photoreceptor Cells/drug effects/pathology/metabolism ; Apoptosis/drug effects ; Retinal Rod Photoreceptor Cells/drug effects/pathology/metabolism ; Disease Models, Animal ; Models, Biological ; },
abstract = {BACKGROUND: Iron-induced oxidative stress was thought to be the reason why the a-wave amplitude of the electroretinogram (ERG) dropped when iron ions were present. It is assumed that reactive oxygen species (ROS) are generated in the presence of iron ions, and this leads to a decrease in hyperpolarization of the photoreceptor. It is known that in age-related macular degeneration (AMD), sodium iodate can induce oxidative stress, apoptosis, and retinal damage, which mimic the effects of clinical AMD. Here, the reduction of the a-wave amplitude in mice with sodium iodate-induced age-related macular degeneration is explained.<br><br>METHODS: The leading edge of the a-wave is divided into voltages developed by cones and rods. The same oxidative stress model is applied here since sodium iodate causes the creation of ROS in a manner similar to that caused by iron ions, with the exception that the retina is treated as a circuit of various resistances when computing the photoresponse. Moreover, sodium iodate also leads to apoptosis and, hence, may cause misalignment in cones (not in rods) during the initial stage of apoptosis in AMD. To include the effects of apoptosis and shortening in cones and rods, we have used a factor representing the fraction of total cones and rods that are alive. To include the effect of misalignment of cones on the reduction of the a-wave amplitude, we have used the Stiles-Crawford function to calculate the number of photoisomerizations occurring in a photoreceptor misaligned at an angle &#x3b8;. The results are compared with experimental data.<br><br>RESULTS: In sodium iodate-treated eyes, the ROS produced can attract calcium ions in the photoreceptor, which increases the calcium influx. In the case of the cones, the inclusion of the misalignment angle in the phototransduction process helps in determining the voltage and slope of the voltage vs. time graph.The smaller the fraction of active photoreceptors, the smaller the amplitude of the a-wave. The calcium influx, misaligned photoreceptors, and total photoreceptor loss all cause the amplitude of the a-wave to decrease, and at any time from the beginning of phototransduction cascade, the calcium influx causes the slope of the a-wave to increase.<br><br>CONCLUSION: The reduction in the a-wave amplitude in the eyes of sodium iodate-treated mice is attributed to oxidative stress in both cones and rods and cone misalignment, which ultimately lead to apoptosis and vision loss in AMD.},
}
@article {pmid38907092,
year = {2024},
author = {Lee, Y and Kim, D and Chung, PED and Lee, M and Kim, N and Chang, J and Lee, BC},
title = {Pre-Clinical Studies of a Novel Bispecific Fusion Protein Targeting C3b and VEGF in Neovascular and Nonexudative AMD Models.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {8},
pages = {2227-2242},
pmid = {38907092},
issn = {2193-8245},
abstract = {INTRODUCTION: KNP-301 is a bi-specific fragment crystallizable region (Fc) fusion protein, which inhibits both C3b and vascular endothelial growth factor (VEGF) simultaneously for patients with late-stage age-related macular degeneration (AMD). The present study evaluated in vitro potency, in vivo efficacy, intravitreal pharmacokinetics (IVT PK), and injectability of KNP-301.<br><br>METHODS: C3b and VEGF binding of KNP-301 were assessed by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA), and cellular bioassays. A laser-induced choroidal neovascularization (CNV) model and a sodium iodate-induced nonexudative AMD model were used to test the in vivo efficacy of mouse surrogate of KNP-301. Utilizing fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) scans, the reduction in disease lesions were analyzed in a CNV mouse model. In the nonexudative AMD mouse model, outer nuclear layer (ONL) was assessed by immunofluorescence staining. Lastly, intravitreal pharmacokinetic study was conducted with New Zealand white rabbits via IVT administration of KNP-301 and injectability of KNP-301 was examined by a viscosity test at high concentrations.<br><br>RESULTS: KNP-301 bound C3b selectively, which resulted in a blockade of the alternative pathway, not the classical pathway. KNP-301 also acted as a VEGF trap, impeding VEGF-mediate signaling. Our dual-blockade strategy was effective in both neovascular and nonexudative AMD models. Moreover, KNP-301 had an advantage of potentially less frequent dosing due to the long half-life in the intravitreal chamber. Our viscosity assessment confirmed that KNP-301 meets the criteria of the IVT injection.<br><br>CONCLUSIONS: Unlike current therapies, KNP-301 is expected to cover patients with late-stage AMD of both neovascular and nonexudative AMD, and its long-term PK profile at the intravitreal chamber would allow convenience in the dosing interval of patients.},
}
@article {pmid38904175,
year = {2024},
author = {},
title = {Expression of Concern: Madecassoside protects retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis through the activation of Nrf2/HO-1 pathway.},
journal = {Bioscience reports},
volume = {44},
number = {6},
pages = {},
doi = {10.1042/BSR-2019-4347_EOC},
pmid = {38904175},
issn = {1573-4935},
mesh = {*NF-E2-Related Factor 2/metabolism ; *Oxidative Stress/drug effects ; *Hydrogen Peroxide/toxicity/pharmacology ; *Apoptosis/drug effects ; Humans ; *Heme Oxygenase-1/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Signal Transduction/drug effects ; Triterpenes/pharmacology ; Epithelial Cells/drug effects/metabolism ; Cell Line ; Membrane Proteins/metabolism/genetics ; Animals ; },
}
@article {pmid38903171,
year = {2024},
author = {Pu, KL and Kang, H and Li, L},
title = {Therapeutic targets for age-related macular degeneration: proteome-wide Mendelian randomization and colocalization analyses.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1400557},
pmid = {38903171},
issn = {1664-2295},
abstract = {BACKGROUND: Currently, effective therapeutic drugs for age-related macular degeneration (AMD) are urgently needed, and it is crucial to explore new treatment targets. The proteome is indispensable for exploring disease targets, so we conducted a Mendelian randomization (MR) of the proteome to identify new targets for AMD and its related subtypes.<br><br>METHODS: The plasma protein level data used in this study were obtained from two large-scale studies of protein quantitative trait loci (pQTL), comprising 35,559 and 54,219 samples, respectively. The expression quantitative trait loci (eQTL) data were sourced from eQTLGen and GTEx Version 8. The discovery set for AMD data and subtypes was derived from the FinnGen study, consisting of 9,721 AMD cases and 381,339 controls, 5,239 wet AMD cases and 273,920 controls, and 6,651 dry AMD cases and 272,504 controls. The replication set for AMD data was obtained from the study by Winkler TW et al., comprising 14,034 cases and 91,234 controls. Summary Mendelian randomization (SMR) analysis was employed to assess the association between QTL data and AMD and its subtypes, while colocalization analysis was performed to determine whether they share causal variants. Additionally, chemical exploration and molecular docking were utilized to validate potential drugs targeting the identified proteins.<br><br>RESULTS: SMR and colocalization analysis jointly identified risk-associated proteins for AMD and its subtypes, including 5 proteins (WARS1, BRD2, IL20RB, TGFB1, TNFRSF10A) associated with AMD, 2 proteins (WARS1, IL20RB) associated with Dry-AMD, and 9 proteins (COL10A1, WARS1, VTN, SDF2, LBP, CD226, TGFB1, TNFRSF10A, CSF2) associated with Wet-AMD. The results revealed potential therapeutic chemicals, and molecular docking indicated a good binding between the chemicals and protein structures.<br><br>CONCLUSION: Proteome-wide MR have identified risk-associated proteins for AMD and its subtypes, suggesting that these proteins may serve as potential therapeutic targets worthy of further clinical investigation.},
}
@article {pmid38902972,
year = {2024},
author = {Liu, Q and Zhang, HY and Zhang, QY and Wang, FS and Zhu, Y and Feng, SG and Jiang, Q and Yan, B},
title = {Olink Profiling of Aqueous Humor Identifies Novel Biomarkers for Wet Age-Related Macular Degeneration.},
journal = {Journal of proteome research},
volume = {23},
number = {7},
pages = {2532-2541},
doi = {10.1021/acs.jproteome.4c00195},
pmid = {38902972},
issn = {1535-3907},
mesh = {*Aqueous Humor/metabolism ; Humans ; *Biomarkers/metabolism ; Male ; *Wet Macular Degeneration/metabolism/genetics ; Female ; *Angiopoietin-like Proteins/metabolism/genetics ; *Angiopoietin-Like Protein 7 ; Choroidal Neovascularization/metabolism/genetics/pathology ; Aged ; Cell Proliferation ; Animals ; Cell Movement ; Mice ; },
abstract = {Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.},
}
@article {pmid38902481,
year = {2024},
author = {Fei, X and Jung, S and Kwon, S and Kim, J and Corson, TW and Seo, SY},
title = {Challenges and opportunities of developing small-molecule therapies for age-related macular degeneration.},
journal = {Archives of pharmacal research},
volume = {47},
number = {6},
pages = {538-557},
pmid = {38902481},
issn = {1976-3786},
support = {R01 EY035159/EY/NEI NIH HHS/United States ; 2020R1C1C1008148//National Research Foundation of Korea/ ; R01EY025641//Retina Research Foundation/ ; R01 EY025641/EY/NEI NIH HHS/United States ; R01 EY031939/EY/NEI NIH HHS/United States ; R01EY035159//Retina Research Foundation/ ; NRF-2022R1A2C1092715//National Research Foundation of Korea/ ; R01EY031939//Retina Research Foundation/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Wet Macular Degeneration/drug therapy ; *Protein-Tyrosine Kinases/antagonists &amp; inhibitors ; *Integrins/antagonists &amp; inhibitors ; Drug Administration Routes ; *Drug Discovery/trends ; Clinical Trials as Topic ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in senior adults. The disease can be categorized into two types: wet AMD and dry AMD. Wet AMD, also known as exudative or neovascular AMD, is less common but more severe than dry AMD and is responsible for 90% of the visual impairment caused by AMD and affects 20 million people worldwide. Current treatment options mainly involve biologics that inhibit the vascular endothelial growth factor or complement pathways. However, these treatments have limitations such as high cost, injection-related risks, and limited efficacy. Therefore, new therapeutic targets and strategies have been explored to improve the outcomes of patients with AMD. A promising approach is the use of small-molecule drugs that modulate different factors involved in AMD pathogenesis, such as tyrosine kinases and integrins. Small-molecule drugs offer advantages, such as oral administration, low cost, good penetration, and increased specificity for the treatment of wet and dry AMD. This review summarizes the current status and prospects of small-molecule drugs for the treatment of wet AMD. These advances are expected to support the development of effective and targeted treatments for patients with AMD.},
}
@article {pmid38901467,
year = {2025},
author = {Prenner, V and Reiter, GS and Fuchs, P and Birner, K and Frank, S and Coulibaly, L and Gumpinger, M and Bogunovic, H and Schmidt-Erfurth, U},
title = {Advancing the visibility of outer retinal integrity in neovascular age-related macular degeneration with high-resolution OCT.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {1},
pages = {42-49},
doi = {10.1016/j.jcjo.2024.05.014},
pmid = {38901467},
issn = {1715-3360},
mesh = {Humans ; *Tomography, Optical Coherence/methods/instrumentation ; Prospective Studies ; Cross-Sectional Studies ; Female ; Male ; *Wet Macular Degeneration/diagnosis/drug therapy ; Aged ; *Retinal Pigment Epithelium/pathology ; *Visual Acuity ; Aged, 80 and over ; Fluorescein Angiography/methods ; Middle Aged ; Fundus Oculi ; },
abstract = {OBJECTIVE: To compare the visibility and accessibility of the outer retina in neovascular age-related macular degeneration (nAMD) between 2 OCT devices.<br><br>METHODS: In this prospective, cross-sectional exploratory study, differences in thickness and loss of individual outer retinal layers in eyes with nAMD and in age-matched healthy eyes between a next-level High-Res OCT device and the conventional SPECTRALIS OCT (both Heidelberg Engineering GmbH, Heidelberg, Germany) were analyzed. Eyes with nAMD and at least 250 nL of retinal fluid, quantified by an approved deep-learning algorithm (Fluid Monitor, RetInSight, Vienna, Austria), fulfilled the inclusion criteria. The outer retinal layers were segmented using automated layer segmentation and were corrected manually. Layer loss and thickness were compared between both devices using a linear mixed-effects model and a paired t test.<br><br>RESULTS: Nineteen eyes of 17 patients with active nAMD and 17 healthy eyes were included. For nAMD eyes, the thickness of the retinal pigment epithelium (RPE) differed significantly between the devices (25.42 &#x3bc;m [95% CI, 14.24-36.61] and 27.31 &#x3bc;m [95% CI, 16.12-38.50] for high-resolution OCT and conventional OCT, respectively; p&#x202f;=&#x202f;0.033). Furthermore, a significant difference was found in the mean relative external limiting membrane loss (p&#x202f;=&#x202f;0.021). However, the thickness of photoreceptors, RPE integrity loss, and photoreceptor integrity loss did not differ significantly between devices in the central 3 mm. In healthy eyes, a significant difference in both RPE and photoreceptor thickness between devices was shown (p < 0.001).<br><br>CONCLUSION: Central RPE thickness was significantly thinner on high-resolution OCT compared with conventional OCT images explained by superior optical separation of the RPE and Bruch's membrane.},
}
@article {pmid38900484,
year = {2024},
author = {Bressler, NM and Freund, KB and Bakri, SJ and Kim, JE and Ferrara, D and Brittain, C and Pickthorn, K and Lin, H and Sun, C and Martin, J},
title = {Intraocular Pressure Outcomes After Lampalizumab Injections in Patients With Geographic Atrophy.},
journal = {JAMA ophthalmology},
volume = {142},
number = {8},
pages = {772-776},
pmid = {38900484},
issn = {2168-6173},
mesh = {Humans ; *Intraocular Pressure/drug effects/physiology ; *Intravitreal Injections ; Female ; Male ; *Geographic Atrophy/drug therapy/physiopathology/diagnosis ; Aged ; Middle Aged ; Tonometry, Ocular ; Visual Acuity/physiology ; Antibodies, Monoclonal/administration &amp; dosage/adverse effects/therapeutic use ; Treatment Outcome ; Double-Blind Method ; Follow-Up Studies ; Immunoglobulin Fab Fragments ; },
abstract = {IMPORTANCE: Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more recently approved intravitreous agents involve volumes from 0.07 to 0.1 mL. It is not well established whether repeated 0.1-mL intravitreous injections may result in IOP-related complications.<br><br>OBJECTIVE: To investigate the effect of 1 year of repeated 0.1-mL intravitreous injections on IOP outcomes.<br><br>This study was a post hoc analysis of 2 clinical trials investigating the IOP safety of intravitreous lampalizumab on geographic atrophy secondary to age-related macular degeneration. Both trials were conducted between 2014 and 2018 and recruited participants who were 50 years or older and had bilateral geographic atrophy. This post hoc analysis was performed between 2018 and 2022.<br><br>INTERVENTIONS: Intravitreous lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks.<br><br>MAIN OUTCOMES AND MEASURES: IOP changes in the 4-week-frequency study arms and ocular adverse events to week 48 in all arms. The hypothesis for this analysis was formulated after data collection.<br><br>RESULTS: Among a total of 1851 participants, there was no change in mean pre-injection IOP values through 48 weeks in either arm. The adverse events glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm.<br><br>CONCLUSIONS AND RELEVANCE: Over 1 year, IOP increases were rare and did not affect treated participants more frequently than sham arm participants. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531.},
}
@article {pmid38899961,
year = {2024},
author = {Arrigo, A and Aragona, E and Del Fabbro, S and Balduzzi, E and Parodi, MB and Bandello, F},
title = {Quantitative Optical Coherence Tomography Detection of New Neovascular Branches and Association With Exudation Recurrence in Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {6},
pages = {30},
pmid = {38899961},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Cross-Sectional Studies ; Aged ; *Wet Macular Degeneration/diagnosis ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Recurrence ; *Visual Acuity/physiology ; Angiogenesis Inhibitors/therapeutic use ; Fundus Oculi ; Retrospective Studies ; Middle Aged ; Exudates and Transudates ; },
abstract = {PURPOSE: The purpose of this study was to investigate the clinical role of multi-signal quantitative optical coherence tomography angiography (OCTA) perfusion sampling in neovascular age-related macular degeneration (AMD).<br><br>METHODS: The study was designed as a cross-sectional case series. We collected data from already treated macular neovascularization (MNV), characterized by (I) clinically relevant recurrent exudation, (II) nonclinically relevant recurrent exudation, and (III) inactive lesion. We proposed a new OCTA metric, calculating the gap between high-resolution (HR) and high-speed (HS) OCTA samplings, hypothesizing that this gap might improve the detection of new secondary MNV branches, being also associated with exudation recurrence. Main outcome measures were the HR-HS gap-based categorization of MNV lesions and the assessment of its association with exudative, minimally exudative, and inactive lesions.<br><br>RESULTS: Our cohort (which consisted of 32 MNV eyes; 32 patients; mean disease duration 5 years) was classified as type 1 (17; 53%), type 2 (11; 34%), or mixed type (4; 13%) MNV. Subretinal fibrosis was found in 17 out of 32 eyes (53%), whereas outer retinal atrophy involved 22 of 32 eyes (69%). HR-HS MNV gap was significantly different among MNV subgroups: 18% for the exudative subgroup, 12% for the minimally exudative subgroup, and 4% for the inactive subgroup. HR-HS gap significantly correlated with best corrected visual acuity (BCVA), disease duration, fibrosis, and outer retinal atrophy.<br><br>CONCLUSIONS: HR-HS gap is a novel quantitative metric to detect the secondary novel branches of AMD-related MNV. This parameter is clinically relevant because it is associated with fluid recurrence. The integration of HR-HS gap in artificial intelligence models might help to predict MNV reactivation and to optimize treatment strategies.},
}
@article {pmid38898138,
year = {2024},
author = {Ozawa, Y and Yoshihara, K and Mezghani, M and Pierzchała, P and Nikodem, M and Barbier, S and Nomoto, M and Aitoku, Y},
title = {Recent daily life burdens associated with neovascular age-related macular degeneration involve difficulties in use of electronic devices.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14181},
pmid = {38898138},
issn = {2045-2322},
mesh = {Humans ; Female ; Male ; Aged ; *Activities of Daily Living ; Aged, 80 and over ; Surveys and Questionnaires ; *Macular Degeneration ; Visual Acuity ; Quality of Life ; Cost of Illness ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a prevalent cause of permanent vision loss and blindness in the elderly worldwide, with a significant impact on patients' daily lives. However, burdens related to nAMD from the patients' perspective have not been well documented. Here we developed a new questionnaire after eliciting nAMD patients' daily challenges followed by a pilot survey. Seven daily life burden domains were identified, and a quantitative survey was conducted using the questionnaire in the real-world clinic. Of the total 153 participants (mean age, 76.3 ± 8.3 years), 67 (43.8%) had bilateral nAMD, and 79 (52.7%) were classified into severe nAMD according to the best-corrected visual acuity with cut-off value of 0.52 in logMAR. Patients with bilateral and severe nAMD had significantly higher burden scores across all domains. Network models for the bilateral and severe disease subgroups identified the interactions between "activity of daily living" and "hand-eye coordination" and between "use of electronic devices" and "face recognition" domains, which were considered to be important burdens for the patients. These results can advance ophthalmologists' understanding of the impact of nAMD on patients' daily lives and the importance of active and continuing treatment for patients with nAMD.},
}
@article {pmid38895690,
year = {2024},
author = {Ying, JN and Li, H and Zhang, YY and Li, WD and Yi, QY},
title = {Application and progress of artificial intelligence technology in the segmentation of hyperreflective foci in OCT images for ophthalmic disease research.},
journal = {International journal of ophthalmology},
volume = {17},
number = {6},
pages = {1138-1143},
pmid = {38895690},
issn = {2222-3959},
abstract = {With the advancement of retinal imaging, hyperreflective foci (HRF) on optical coherence tomography (OCT) images have gained significant attention as potential biological biomarkers for retinal neuroinflammation. However, these biomarkers, represented by HRF, present pose challenges in terms of localization, quantification, and require substantial time and resources. In recent years, the progress and utilization of artificial intelligence (AI) have provided powerful tools for the analysis of biological markers. AI technology enables use machine learning (ML), deep learning (DL) and other technologies to precise characterization of changes in biological biomarkers during disease progression and facilitates quantitative assessments. Based on ophthalmic images, AI has significant implications for early screening, diagnostic grading, treatment efficacy evaluation, treatment recommendations, and prognosis development in common ophthalmic diseases. Moreover, it will help reduce the reliance of the healthcare system on human labor, which has the potential to simplify and expedite clinical trials, enhance the reliability and professionalism of disease management, and improve the prediction of adverse events. This article offers a comprehensive review of the application of AI in combination with HRF on OCT images in ophthalmic diseases including age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and other retinal diseases and presents prospects for their utilization.},
}
@article {pmid38895680,
year = {2024},
author = {Vahidi, A and Khosravi, T and Dastaviz, F and Sheikh Arabi, M and Khosravi, A and Oladnabi, M},
title = {Niosome-encapsulated auraptene reduced the mRNA expression of VEGF-A and PDGFs genes in human retina-derived RPE cell line.},
journal = {International journal of ophthalmology},
volume = {17},
number = {6},
pages = {1028-1035},
pmid = {38895680},
issn = {2222-3959},
abstract = {AIM: To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor (VEGF)-A and platelet-derived growth factors (PDGFs) in human retinal pigment epithelium (RPE) cell line.<br><br>METHODS: Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80. RPE cell line was treated with both free AUR and niosome-encapsulated. Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of VEGF-A and PDGF-A, PDGF-B, PDGF-C, PDGF-D genes was measured after total RNA extraction and cDNA synthesis, using real-time polymerase chain reaction (RT-PCR).<br><br>RESULTS: The highest entrapment efficiency (EE) was achieved by Span 60:cholesterol (1:1) with 64.3%. The half maximal inhibitory concentration (IC50) of free and niosome-encapsulated AUR were 38.5 and 27.78 &#xb5;g/mL, respectively. Release study revealed that niosomal AUR had more gradual delivery to the cells. RT-PCR results showed reduced expression levels of VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D after treatment with both free and niosomal AUR.<br><br>CONCLUSION: Niosomal formulation of Span 60: cholesterol (1:1) is an effective drug delivery approach to transfer AUR to RPE cells. VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D are four angiogenic factors, inhibiting which by niosomal AUR may be effective in age-related macular degeneration.},
}
@article {pmid38892804,
year = {2024},
author = {Tiosano, L and Abutbul, R and Lender, R and Shwartz, Y and Chowers, I and Hoshen, Y and Levy, J},
title = {Anomaly Detection and Biomarkers Localization in Retinal Images.},
journal = {Journal of clinical medicine},
volume = {13},
number = {11},
pages = {},
pmid = {38892804},
issn = {2077-0383},
support = {3485-19//Israel Science Foundation/ ; },
abstract = {Background: To design a novel anomaly detection and localization approach using artificial intelligence methods using optical coherence tomography (OCT) scans for retinal diseases. Methods: High-resolution OCT scans from the publicly available Kaggle dataset and a local dataset were used by four state-of-the-art self-supervised frameworks. The backbone model of all the frameworks was a pre-trained convolutional neural network (CNN), which enabled the extraction of meaningful features from OCT images. Anomalous images included choroidal neovascularization (CNV), diabetic macular edema (DME), and the presence of drusen. Anomaly detectors were evaluated by commonly accepted performance metrics, including area under the receiver operating characteristic curve, F1 score, and accuracy. Results: A total of 25,315 high-resolution retinal OCT slabs were used for training. Test and validation sets consisted of 968 and 4000 slabs, respectively. The best performing across all anomaly detectors had an area under the receiver operating characteristic of 0.99. All frameworks were shown to achieve high performance and generalize well for the different retinal diseases. Heat maps were generated to visualize the quality of the frameworks' ability to localize anomalous areas of the image. Conclusions: This study shows that with the use of pre-trained feature extractors, the frameworks tested can generalize to the domain of retinal OCT scans and achieve high image-level ROC-AUC scores. The localization results of these frameworks are promising and successfully capture areas that indicate the presence of retinal pathology. Moreover, such frameworks have the potential to uncover new biomarkers that are difficult for the human eye to detect. Frameworks for anomaly detection and localization can potentially be integrated into clinical decision support and automatic screening systems that will aid ophthalmologists in patient diagnosis, follow-up, and treatment design. This work establishes a solid basis for further development of automated anomaly detection frameworks for clinical use.},
}
@article {pmid38892791,
year = {2024},
author = {Tang, WSW and Lau, NXM and Krishnan, MN and Chin, YC and Ho, CSH},
title = {Depression and Eye Disease-A Narrative Review of Common Underlying Pathophysiological Mechanisms and their Potential Applications.},
journal = {Journal of clinical medicine},
volume = {13},
number = {11},
pages = {},
pmid = {38892791},
issn = {2077-0383},
abstract = {Background: Depression has been shown to be associated with eye diseases, including dry eye disease (DED), cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). This narrative review explores potential pathophysiological connections between depression and eye disease, as well as its potential correlations with ocular parameters. Methods: A literature search was conducted in August 2022 in PUBMED, EMBASE, and PsycINFO. Published articles related to the subject were consolidated and classified according to respective eye diseases and pathophysiological mechanisms. Results: The literature reviewed suggests that common pathophysiological states like inflammation and neurodegeneration may contribute to both depression and certain eye diseases, while somatic symptoms and altered physiology, such as disruptions in circadian rhythm due to eye diseases, can also influence patients' mood states. Grounded in the shared embryological, anatomical, and physiological features between the eye and the brain, depression is also correlated to changes observed in non-invasive ophthalmological imaging modalities, such as changes in the retinal nerve fibre layer and retinal microvasculature. Conclusions: There is substantial evidence of a close association between depression and eye diseases. Understanding the underlying concepts can inform further research on treatment options and monitoring of depression based on ocular parameters.},
}
@article {pmid38892113,
year = {2024},
author = {Chen, X and Xu, Y and Ju, Y and Gu, P},
title = {Metabolic Regulation of Endothelial Cells: A New Era for Treating Wet Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {25},
number = {11},
pages = {},
pmid = {38892113},
issn = {1422-0067},
support = {2022YFA1105502, 2022YFA1105500//National Key R&amp;D program of China/ ; },
mesh = {Humans ; *Endothelial Cells/metabolism ; *Wet Macular Degeneration/metabolism/drug therapy ; Animals ; Vascular Endothelial Growth Factor A/metabolism ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use/pharmacology ; Metabolic Networks and Pathways ; Neovascularization, Pathologic/metabolism ; },
abstract = {Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.},
}
@article {pmid38891923,
year = {2024},
author = {Delle, C and Wang, X and Nedergaard, M},
title = {The Ocular Glymphatic System-Current Understanding and Future Perspectives.},
journal = {International journal of molecular sciences},
volume = {25},
number = {11},
pages = {},
pmid = {38891923},
issn = {1422-0067},
support = {R01 AT011439/AT/NCCIH NIH HHS/United States ; R01 AT012707/AT/NCCIH NIH HHS/United States ; },
mesh = {Humans ; *Glymphatic System/physiology/metabolism ; Animals ; Optic Nerve/metabolism/physiology ; Retina/metabolism/physiology ; Eye/metabolism ; Glaucoma/metabolism/physiopathology/pathology ; },
abstract = {The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic.},
}
@article {pmid38890703,
year = {2024},
author = {Jiménez-Loygorri, JI and Viedma-Poyatos, &#xc1; and Gómez-Sintes, R and Boya, P},
title = {Urolithin A promotes p62-dependent lysophagy to prevent acute retinal neurodegeneration.},
journal = {Molecular neurodegeneration},
volume = {19},
number = {1},
pages = {49},
pmid = {38890703},
issn = {1750-1326},
mesh = {Animals ; Mice ; *Coumarins/pharmacology ; Autophagy/drug effects/physiology ; Macular Degeneration/metabolism/pathology ; Retina/metabolism/drug effects/pathology ; Mitophagy/drug effects/physiology ; Sequestosome-1 Protein/metabolism ; Lysosomes/metabolism/drug effects ; Humans ; Disease Models, Animal ; Neuroprotective Agents/pharmacology ; Mice, Inbred C57BL ; Iodates/toxicity ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people in the developed world, and the number of people affected is expected to almost double by 2040. The retina presents one of the highest metabolic demands in our bodies that is partially or fully fulfilled by mitochondria in the neuroretina and retinal pigment epithelium (RPE), respectively. Together with its post-mitotic status and constant photooxidative damage from incoming light, the retina requires a tightly-regulated housekeeping system that involves autophagy. The natural polyphenol Urolithin A (UA) has shown neuroprotective benefits in several models of aging and age-associated disorders, mostly attributed to its ability to induce mitophagy and mitochondrial biogenesis. Sodium iodate (SI) administration recapitulates the late stages of AMD, including geographic atrophy and photoreceptor cell death.<br><br>METHODS: A combination of in vitro, ex vivo and in vivo models were used to test the neuroprotective potential of UA in the SI model. Functional assays (OCT, ERGs), cellular analysis (flow cytometry, qPCR) and fine confocal microscopy (immunohistochemistry, tandem selective autophagy reporters) helped address this question.<br><br>RESULTS: UA alleviated neurodegeneration and preserved visual function in SI-treated mice. Simultaneously, we observed severe proteostasis defects upon SI damage induction, including autophagosome accumulation, that were resolved in animals that received UA. Treatment with UA restored autophagic flux and triggered PINK1/Parkin-dependent mitophagy, as previously reported in the literature. Autophagy blockage caused by SI was caused by severe lysosomal membrane permeabilization. While UA did not induce lysosomal biogenesis, it did restore upcycling of permeabilized lysosomes through lysophagy. Knockdown of the lysophagy adaptor SQSTM1/p62 abrogated viability rescue by UA in SI-treated cells, exacerbated lysosomal defects and inhibited lysophagy.<br><br>CONCLUSIONS: Collectively, these data highlight a novel putative application of UA in the treatment of AMD whereby it bypasses lysosomal defects by promoting p62-dependent lysophagy to sustain proteostasis.},
}
@article {pmid38888805,
year = {2024},
author = {Stolwijk, ML and Meyer, I and van der Pas, SL and Twisk, JWR and van Nispen, RMA and van Rens, GHMB},
title = {Low vision aids provision in an urban setting in Germany between 2014 and 2017: a regional population based study with healthcare claims data.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3711-3723},
pmid = {38888805},
issn = {1435-702X},
support = {Visio Foundation//Visio Foundation/ ; },
mesh = {Humans ; Female ; Male ; Germany/epidemiology ; Retrospective Studies ; Middle Aged ; *Vision, Low/epidemiology ; Aged ; Adult ; *Urban Population/statistics &amp; numerical data ; Young Adult ; Adolescent ; Visual Acuity ; Child ; Child, Preschool ; Aged, 80 and over ; Infant ; Insurance Claim Review/statistics &amp; numerical data ; Databases, Factual ; Population Surveillance ; },
abstract = {PURPOSE: Little is known about the utilization of low vision services (LVS) in Germany. To understand which persons and how often these services would be utilized, this study aimed to investigate low vision aids (LVAs) provision in an urban setting and to describe user characteristics and trends in their characteristics.<br><br>METHODS: A retrospective study based on a population-based healthcare claims database in Cologne (N&#x2009;=&#x2009;~&#x2009;500,000), Germany. The study population comprised individuals, who were continuously insured at four large statutory health insurers and who redeemed a prescription for visual aids or aids for blindness between January 2014 and December 2017. We examined their socio-demographic and clinical characteristics. Trends in characteristics were examined with logistic and linear regression models over time.<br><br>RESULTS: Out of ~&#x2009;500,000 persons, 781 unique individuals (~&#x2009;0.2%) redeemed an LVA prescription. They were mainly female (68.7%), 60 years or older (75.3%) and had macular degeneration (50.6%) and/or glaucoma (25.9%). In the working-age subgroup, 33.8% were employed. Visual aids were most often prescribed (74.1%) and of all types of LVAs, individuals most commonly redeemed a prescription for magnifiers (35.8%), screen readers (34.3%) and/or canes (17.1%). Of the entire study population, 75.4% received their prescription from an ophthalmologist, 5.3% from a general practitioner and 7.1% from other medical specialists. Significant trends in characteristics of individuals who redeemed an LVA prescription were not found.<br><br>CONCLUSIONS: Between 2014 and 2017, 781 individuals in Cologne redeemed an LVA prescription. They had characteristics which mostly can be explained by the epidemiology of VI. Results indicate that individuals that redeemed LVAs have a magnification requirement of &#x2265;&#x2009;1.5-fold and &#x2265;&#x2009;6-fold. Furthermore, next to ophthalmologists, general practitioners and other medical specialists seem to play a role in LVA provision as well, which should be taken into account by policy makers when planning interventions for increasing LVS provision. Our findings provide a starting point to examine LVS provision in Germany.},
}
@article {pmid38886462,
year = {2024},
author = {Deussen, DN and Heinke, A and Elsner, W and Galang, CMB and Kalaw, FGP and Warter, A and Bartsch, DU and Cheng, L and Freeman, WR},
title = {Effect of manual OCTA segmentation correction to improve image quality and visibility of choroidal neovascularization in AMD.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13990},
pmid = {38886462},
issn = {2045-2322},
support = {P30EY022589/EY/NEI NIH HHS/United States ; R01EY033847/GF/NIH HHS/United States ; P30 EY022589/EY/NEI NIH HHS/United States ; R01 EY016323/EY/NEI NIH HHS/United States ; OT2OD032644/GF/NIH HHS/United States ; OT2 OD032644/OD/NIH HHS/United States ; R01 EY033847/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroidal Neovascularization/diagnostic imaging/pathology ; *Tomography, Optical Coherence/methods ; Female ; Male ; Retrospective Studies ; Aged ; *Macular Degeneration/diagnostic imaging/pathology/complications ; Aged, 80 and over ; Image Processing, Computer-Assisted/methods ; Middle Aged ; Fluorescein Angiography/methods ; },
abstract = {In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch's Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.},
}
@article {pmid38886213,
year = {2024},
author = {Im, S and Song, MH and Elangovan, M and Woo, KM and Park, WJ},
title = {The matricellular protein CCN5 prevents anti-VEGF drug-induced epithelial-mesenchymal transition of retinal pigment epithelium.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13920},
pmid = {38886213},
issn = {2045-2322},
support = {2022R1A2C1004256//National Research Foundation of Korea/ ; },
mesh = {*Epithelial-Mesenchymal Transition/drug effects ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Animals ; Humans ; Mice ; *Vascular Endothelial Growth Factor A/metabolism ; Macular Degeneration/metabolism/pathology/drug therapy/chemically induced ; Cell Line ; Bevacizumab/pharmacology ; CCN Intercellular Signaling Proteins/metabolism/genetics ; Angiogenesis Inhibitors/pharmacology ; Ranibizumab/pharmacology ; Recombinant Fusion Proteins/pharmacology ; Signal Transduction/drug effects ; Repressor Proteins ; Receptors, Vascular Endothelial Growth Factor ; },
abstract = {Age-related macular degeneration (AMD) is one of the major causes of blindness in the elderly worldwide. Anti-vascular endothelial growth factor (VEGF) drugs have been widely used to treat the neovascular type of AMD (nAMD). However, VEGF acts not only as a pro-angiogenic factor but also as an anti-apoptotic factor in the eyes. In this study, we found that anti-VEGF drugs, including bevacizumab (Bev), ranibizumab (Ran), and aflibercept (Afl), induced epithelial-mesenchymal transition (EMT) in ARPE-19 cells in vitro, accompanied by the induction of CCN2, a potent pro-fibrotic factor. Similarly, intravitreal injection of Afl into mouse eyes resulted in EMT in the retinal pigmented epithelium (RPE). Co-treatment with CCN5, an anti-fibrotic factor that down-regulates CCN2 expression, significantly attenuated the adverse effects of the anti-VEGF drugs both in vitro and in vivo. Inhibition of the VEGF signaling pathway with antagonists of VEGF receptors, SU5416 and ZM323881, induced EMT and up-regulated CCN2 in ARPE-19 cells. Additionally, knock-down of CCN2 with siRNA abolished the adverse effects of the anti-VEGF drugs in ARPE-19 cells. Collectively, these results suggest that anti-VEGF drugs induce EMT in RPE through the induction of CCN2 and that co-treatment with CCN5 attenuates the adverse effects of anti-VEGF drugs in mouse eyes.},
}
@article {pmid38884553,
year = {2024},
author = {Cheng, Y and Hiya, F and Li, J and Shen, M and Liu, J and Herrera, G and Berni, A and Morin, R and Joseph, J and Zhang, Q and Gregori, G and Rosenfeld, PJ and Wang, RK},
title = {Calcified Drusen Prevent the Detection of Underlying Choriocapillaris Using Swept-Source Optical Coherence Tomography Angiography.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {6},
pages = {26},
pmid = {38884553},
issn = {1552-5783},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; R01 EY028753/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; *Retinal Drusen/diagnostic imaging/diagnosis ; Female ; Aged ; Male ; *Fluorescein Angiography/methods ; Regional Blood Flow/physiology ; Calcinosis/diagnostic imaging/diagnosis ; Aged, 80 and over ; Macular Degeneration/diagnosis/physiopathology/diagnostic imaging ; Middle Aged ; Phantoms, Imaging ; Fundus Oculi ; },
abstract = {PURPOSE: In age-related macular degeneration (AMD), choriocapillaris flow deficits (CCFDs) under soft drusen can be measured using established compensation strategies. This study investigated whether CCFDs can be quantified under calcified drusen (CaD).<br><br>METHODS: CCFDs were measured in normal eyes (n = 30) and AMD eyes with soft drusen (n = 30) or CaD (n = 30). CCFD density masks were generated to highlight regions with higher CCFDs. Masks were also generated for soft drusen and CaD based on both structural en face OCT images and corresponding B-scans. Dice similarity coefficients were calculated between the CCFD density masks and both the soft drusen and CaD masks. A phantom experiment was conducted to simulate the impact of light scattering that arises from CaD.<br><br>RESULTS: Area measurements of CCFDs were highly correlated with those of CaD but not soft drusen, suggesting an association between CaD and underlying CCFDs. However, unlike soft drusen, the detected optical coherence tomography (OCT) signals underlying CaD did not arise from the defined CC layer but were artifacts caused by the multiple scattering property of CaD. Phantom experiments showed that the presence of highly scattering material similar to the contents of CaD caused an artifactual scattering tail that falsely generated a signal in the CC structural layer but the underlying flow could not be detected. Similarly, CaD also caused an artifactual scattering tail and prevented the penetration of light into the choroid, resulting in en face hypotransmission defects and an inability to detect blood flow within the choriocapillaris. Upon resolution of the CaD, the CC perfusion became detectable.<br><br>CONCLUSIONS: The high scattering property of CaD leads to a scattering tail under these drusen that gives the illusion of a quantifiable optical coherence tomography angiography signal, but this signal does not contain the angiographic information required to assess CCFDs. For this reason, CCFDs cannot be reliably measured under CaD, and CaD must be identified and excluded from macular CCFD measurements.},
}
@article {pmid38884546,
year = {2024},
author = {Tan, ACS and Peterson, CL and Htoon, HM and Tan, LLY and Tan, Y and Sim, KT and Ong, L and Tan, ZK and Heng, SH and Yeo, IYS and Wong, TY and Cheung, G and Man, R and Fenwick, EK and Lamoureux, E},
title = {Development and Validation of Performance-Based Assessment of Daily Living Tasks in Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {6},
pages = {9},
pmid = {38884546},
issn = {2164-2591},
mesh = {Humans ; *Activities of Daily Living ; *Macular Degeneration/physiopathology/diagnosis ; Female ; Male ; Aged ; *Visual Acuity/physiology ; Reproducibility of Results ; Aged, 80 and over ; Middle Aged ; Vision Tests/methods ; Vision, Binocular/physiology ; Reading ; },
abstract = {PURPOSE: To establish the reliability and validity of five performance-based activities of daily living task tests (ADLTT), to correlate structure to function, to evaluate the impact of visual impairment (VI) on age-related macular degeneration (AMD), and to develop new outcome measures.<br><br>METHODS: A multidisciplinary team developed five ADLTTs: (1) reading test (RT); (2) facial expression (FE) recognition; (3) item search (IS) task; (4) money counting (MC) task; and (5) making a drink (MD), tested with binocular and monocular vision. ADLTTs were tested for known-group (i.e., difference between AMD group and controls) and convergent (i.e., correlation to other measures of visual function), validity metrics, and test-retest reliability in 36 patients with VI (visual acuity (logMAR VA > 0.4) in at least one eye caused by AMD versus 36 healthy controls without VI.<br><br>RESULTS: Compared to controls, AMD patients had a slower reading speed (-77.41 words/min; P < 0.001); took longer to complete MC using monocular worse eye and binocular vision (15.13 seconds and 4.06 seconds longer compared to controls, respectively; P < 0.001); and MD using monocular worse eye vision (9.37 sec; P = 0.033), demonstrating known-group validity. Only RT and MC demonstrated convergent validity, showing correlations with VA, contrast sensitivity, and microperimetry testing. Moderate to good test-retest reliability was observed for MC and MD (interclass correlation coefficient = 0.55 and 0.77; P < 0.001) using monocular worse eye vision.<br><br>CONCLUSIONS: Real-world ADL functioning associated with VI-related AMD can be assessed with our validated ADLTTs, particularly MC and MD.<br><br>TRANSLATIONAL RELEVANCE: This study validates visual function outcome measures that are developed for use in future clinical practice and clinical trials.},
}
@article {pmid38882238,
year = {2023},
author = {Wang, G and Ott, J},
title = {Digenic Analysis Finds Highly Interactive Genetic Variants Underlying Polygenic Traits.},
journal = {Medical research archives},
volume = {11},
number = {10},
pages = {},
pmid = {38882238},
issn = {2375-1916},
support = {R01 AG076901/AG/NIA NIH HHS/United States ; },
abstract = {We briefly review our recently published approach to mining digenic genotype patterns, which consist of two genotypes each originating in a different DNA variant. We do this for a genetic case-control study by evaluating all possible pairs of genotypes, distributing the workload over numerous CPUs (threads) in a high-performance computing environment and apply our methods to two known datasets, age-related macular degeneration (AMD) and Parkinson Disease (PD). Based on a list of (e.g., 100,000) genotype pairs with largest genotype pair frequency differences between cases and controls, we determine the number N u of unique variants occurring in this list. For each unique variant, we find the number of genotype pairs it participates in, which identifies a set of variants "connected" with the given unique variant. Among the total of variants "connected" with all unique variants, only a subset of variants is unique. The ratio of all connected variants divided by that subset of variants is a measure for the overall density or connectedness of variants interacting with each other. We find that variants for the AMD data are much more interconnected than those for PD, at least based on the 100,000 genotype pairs with largest chi-square we investigated. Further, for each of the N u unique variants, we use the number of variants connected with it as a test statistic, weighted by the inverse of the rank at which the unique variant first occurred in the original list of genotype patterns. This weighing scheme ties the number of connections to the genetics of the trait and allows us to obtain, for each of the N u unique variants, an empirical significance level by permuting ranks. We find 12 and 8 significant, highly connected variants for AMD and PD, respectively, some of which have previously been identified by other machine learning methods, thus providing credence to our approach. Among the 100,000 genotype pairs investigated for each of AMD and PD, significant variants showed connections with up to 7,093 and 3,777 other variants, respectively. Our approach has been implemented in a freely available piece of software, the Digenic Network Test. Thus, our statistical genetics method can provide important information on the genetic architecture of polygenic traits.},
}
@article {pmid38881707,
year = {2024},
author = {Garg, SJ and Hadziahmetovic, M},
title = {Verteporfin Photodynamic Therapy for the Treatment of Chorioretinal Conditions: A Narrative Review.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {1701-1716},
pmid = {38881707},
issn = {1177-5467},
abstract = {Photodynamic therapy (PDT) with verteporfin involves intravenous administration of a photosensitizer followed by its laser light activation at the target site to inhibit aberrant choroidal vascularization. This narrative review provides an overview of the role verteporfin PDT plays in the management of chorioretinal conditions. A PubMed literature review of all English-language articles published through October 19, 2023, was conducted to identify relevant references. Verteporfin PDT has been shown to be safe and effective for the treatment of patients with choroidal neovascularization (CNV) due to neovascular age-related macular degeneration and is often used in combination with a vascular endothelial growth factor (VEGF) inhibitor. Additionally, patients with polypoidal choroidal vasculopathy, a subtype of neovascular age-related macular degeneration, also benefit from verteporfin PDT combined with a VEGF inhibitor for improving visual acuity. Verteporfin PDT has also been effective in treating patients with peripapillary CNV, as well as eyes with CNV due to ocular histoplasmosis and pathologic myopia. Reduced dose and/or fluence PDT protocols have been effective in patients with central serous chorioretinopathy while reducing adverse effects. In eyes with choroidal hemangioma, tumor regression and visual outcomes have been improved with verteporfin PDT treatment. Photodynamic therapy with verteporfin continues to play an important role in the management of chorioretinal conditions.},
}
@article {pmid38881613,
year = {2024},
author = {Wolf, J and Chemudupati, T and Kumar, A and Franco, JA and Montague, AA and Lin, CC and Lee, WS and Fisher, AC and Goldberg, JL and Mruthyunjaya, P and Chang, RT and Mahajan, VB},
title = {Using Electronic Health Record Data to Determine the Safety of Aqueous Humor Liquid Biopsies for Molecular Analyses.},
journal = {Ophthalmology science},
volume = {4},
number = {5},
pages = {100517},
pmid = {38881613},
issn = {2666-9145},
abstract = {PURPOSE: Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHRs) is cumbersome, but free-text software tools could facilitate efficient searches.<br><br>DESIGN: Retrospective case series.<br><br>PARTICIPANTS: A total of 1418 aqueous humor liquid biopsies from patients undergoing intraocular surgery.<br><br>METHODS: Free-text EHR searches were performed using the Stanford Research Repository cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed.<br><br>MAIN OUTCOME MEASURES: Biopsy-associated intraoperative complications and endophthalmitis.<br><br>RESULTS: A total of 1418 aqueous humor liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50- to 100-&#x3bc;L sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was >7&#xa0;months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis.<br><br>CONCLUSIONS: Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of aqueous humor samples for molecular analyses. Free-text EHR searches are an efficient approach to reviewing intraoperative procedures.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38881608,
year = {2024},
author = {Fevrier, H and LaPrise, A and Mbagwu, M and Leng, T and Torres, AZ and Borkar, DS},
title = {Comparison of Methods of Clinical Trial Emulation Utilizing Data From the Comparison of AMD Treatment Trial (CATT) and the IRIS® Registry.},
journal = {Ophthalmology science},
volume = {4},
number = {5},
pages = {100524},
pmid = {38881608},
issn = {2666-9145},
abstract = {PURPOSE: We used exact matching and inverse propensity score weighting (IPSW) using real-world data (RWD) from the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) to emulate the 2 pro re nata (prn) treatment arms from the Comparison of AMD Treatment Trial (CATT) and to compare the outcomes of the RWD arms to the 2 monthly treatment arms from the clinical trial.<br><br>DESIGN: Retrospective cohort study utilizing deidentified electronic health record registry data and patient-level deidentified clinical trial data.<br><br>SUBJECTS: All treatment-naive patient eyes with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab only for 1&#xa0;year from either the CATT or the IRIS Registry.<br><br>METHODS: Patients were identified in the IRIS Registry between October 1, 2015 and December 31, 2019. After all nonimaging-based inclusion and exclusion criteria from the CATT were applied, patient eyes receiving bevacizumab or ranibizumab only on a prn basis were identified as the eligible cohort. Exact matching and ISPW was applied based on age, gender, and baseline visual acuity.<br><br>MAIN OUTCOME MEASURES: Mean change in visual acuity, in approximated ETDRS letters, between baseline and 1 year for the IRIS Registry prn treatment arms generated by exact matching and IPSW.<br><br>RESULTS: We identified 427 eyes treated with ranibizumab prn and 771 eyes treated with bevacizumab prn. Using exact matching, 98% (n&#xa0;=&#xa0;281) of CATT patient eyes in the bevacizumab monthly treatment arm and 87% (n&#xa0;=&#xa0;261) of CATT patient eyes in the ranibizumab monthly treatment arm were matched to a patient eye in the IRIS Registry. For the ranibizumab prn treatment arm, patient eyes generated using exact matching gained 1.9 letters and those generated using IPSW gained 2.8 letters (exact matching: 1.9 letters&#xa0;&#xb1;&#xa0;14.0 vs. IPSW: 2.8 letters&#xa0;&#xb1;&#xa0;15.0 letters, P&#xa0;=&#xa0;0.43). For the bevacizumab prn treatment arm, patient eyes generated using exact matching gained 2.4 letters and those generated using IPSW gained 2.1 letters (exact matching: 2.4 letters&#xa0;&#xb1;&#xa0;15.4 vs. IPSW: 2.1 letters&#xa0;&#xb1;&#xa0;16.0 letters, P&#xa0;=&#xa0;0.79).<br><br>CONCLUSIONS: Both exact matching and IPSW produced similar results in emulating the prn treatment arms of the CATT using IRIS Registry data and patient-level clinical trial data. Similar to prior real-world studies, the clinical outcomes were significantly worse in the IRIS Registry treatment arms compared with the clinical trial.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38881600,
year = {2024},
author = {Muqit, MMK and Le Mer, Y and Olmos de Koo, L and Holz, FG and Sahel, JA and Palanker, D},
title = {Prosthetic Visual Acuity with the PRIMA Subretinal Microchip in Patients with Atrophic Age-Related Macular Degeneration at 4 Years Follow-up.},
journal = {Ophthalmology science},
volume = {4},
number = {5},
pages = {100510},
pmid = {38881600},
issn = {2666-9145},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; R01 EY027786/EY/NEI NIH HHS/United States ; R01 EY033049/EY/NEI NIH HHS/United States ; },
abstract = {OBJECTIVE: To assess the efficacy and safety of the PRIMA neurostimulation system with a subretinal microchip for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months postimplantation.<br><br>DESIGN: Feasibility clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.govNCT03333954).<br><br>SUBJECTS: Five patients with GA, no foveal light perception, and VA of logarithm of the minimum angle of resolution (logMAR) 1.3 to 1.7 (20/400-20/1000) in their worse-seeing "study" eye.<br><br>METHODS: In patients subretinally implanted with a photovoltaic neurostimulation array containing 378 pixels of 100 &#x3bc;m in size, the VA was measured with and without the PRIMA system using ETDRS charts at 1 m. The system's external components, augmented reality glasses, and pocket computer provide image processing capabilities, including zoom.<br><br>MAIN OUTCOME MEASURES: Visual acuity using ETDRS charts with and without the system, as well as light sensitivity in the central visual field, measured by Octopus perimetry. Anatomical outcomes demonstrated by fundus photography and OCT up to 48 months postimplantation.<br><br>RESULTS: All 5 subjects met the primary end point of light perception elicited by the implant in the scotoma area. In 1 patient, the implant was incorrectly inserted into the choroid. One subject died 18 months postimplantation due to study-unrelated reasons. ETDRS VA results for the remaining 3 subjects are reported here. Without zoom, VA closely matched the pixel size of the implant: 1.17 &#xb1; 0.13 pixels, corresponding to a mean logMAR of 1.39, or Snellen of 20/500, ranging from 20/438 to 20/565. Using zoom at 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (standard error 5.1) 95% confidence intervals (13.4, 49.9; P < 0.0001). Natural peripheral visual function in the treated eye did not decline after surgery or during the 48-month follow-up period (P&#xa0;= 0.08).<br><br>CONCLUSIONS: Subretinal implantation of PRIMA in subjects with GA experiencing profound vision loss due to AMD is feasible and well tolerated, with no reduction of natural peripheral vision up to 48 months. Prosthetic central vision provided by photovoltaic neurostimulation enabled patients to reliably recognize letters and sequences of letters, and with zoom, it improved VA of up to 8 ETDRS lines.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38881599,
year = {2024},
author = {Patel, S and Storey, PP and Barakat, MR and Hershberger, V and Bridges, WZ and Eichenbaum, DA and Lally, DR and Boyer, DS and Bakri, SJ and Roy, M and Paggiarino, DA},
title = {Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {5},
pages = {100527},
pmid = {38881599},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan-VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy.<br><br>DESIGN: Phase I, multicenter, prospective, open-label, dose-escalation trial.<br><br>PARTICIPANTS: Patients with wAMD and evidence of prior anti-VEGF therapy response.<br><br>METHODS: Patients received a single intravitreal injection of EYP-1901.<br><br>MAIN OUTCOME MEASURES: The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates.<br><br>RESULTS: Seventeen patients enrolled in the 440 &#x3bc;g (3 patients), 1030 &#x3bc;g (1 patient), 2060 &#x3bc;g (8 patients), and 3090 &#x3bc;g (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was&#xa0;-1.8 letters and&#xa0;-5.4 letters at 6 and 12 months. Mean change from baseline in CST was&#xa0;+1.7 &#x3bc;m and&#xa0;+2.4 &#x3bc;m at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months.<br><br>CONCLUSION: In the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety.<br><br>FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid38880376,
year = {2024},
author = {Kalavar, M and Lovett, EA and Nicholas, MP and Ross-Hirsch, A and Nirwan, RS and Sridhar, J and Patel, S and Flynn, HW and Albini, TA and Kuriyan, AE},
title = {Update on "Cell Therapy" Clinics Offering Treatments of Ocular Conditions Using Direct-To-Consumer Marketing Websites in the U.S.},
journal = {American journal of ophthalmology},
volume = {267},
number = {},
pages = {135-141},
doi = {10.1016/j.ajo.2024.06.014},
pmid = {38880376},
issn = {1879-1891},
mesh = {Humans ; United States ; *Direct-to-Consumer Advertising ; *Cell- and Tissue-Based Therapy ; *Eye Diseases/therapy ; *Internet ; United States Food and Drug Administration ; Marketing of Health Services ; Ambulatory Care Facilities ; },
abstract = {PURPOSE: To assess the scope of U.S.-based companies advertising and administering non-Federal Drug Administration (FDA) approved cell-based therapy (herein called NFACT) for ocular conditions based on information from companies' public websites after the FDA's legal actions against specific NFACT clinics in 2018 and 2019. Current findings are compared to previously published data from 2017.<br><br>DESIGN: Trend study looking at U.S.-based companies that use direct-to-consumer marketing and have websites advertising therapy for ocular conditions.<br><br>METHODS: A systematic and extensive keyword-based Internet search was utilized to identify, document, and analyze U.S. business websites offering NFACT for ocular conditions as of August 2022. Main outcomes measured include, clinic locations, marketed ocular conditions, types of NFACT offered, source of stem cells used, routes of administration, and treatment costs.<br><br>RESULTS: From the prior analysis in 2017 to the 2019 analysis, there was a decrease in the number of NFACT clinics from 76 to 62 and companies from 40 to 39. Given the concerning persistence of NFACTs in August 2019 an additional analysis was performed in 2022 which showed a drastic decrease in NFACT clinics from 62 in 2019 to 18 in 2023 and from 39 companies to 13 in 2023. In both 2019 and 2022, the most commonly referenced ocular condition was age-related macular degeneration (2019-72%, 2022-92%). The state with the most clinics was in Texas (2019-12; 2022-5). Autologous adipose-derived stem cells were the most common cell type used in both analyses.<br><br>CONCLUSIONS: In 2019 U.S.-based direct-to-consumer companies marketing NFACT persisted despite (1) a lack of high-quality clinical evidence supporting the efficacy of these procedures, (2) the association of some of these treatments with severe vision loss, and (3) increasing FDA oversight and recent legal action. In 2022 the number of clinics and companies decreased, but their persistence is a reminder that continued concern is necessary and ophthalmic associations need to continue advocacy efforts to protect patients from these potentially predatory organizations.},
}
@article {pmid38879998,
year = {2024},
author = {Wang, TJ and Rethi, L and Ku, MY and Nguyen, HT and Chuang, AE},
title = {A review on revolutionizing ophthalmic therapy: Unveiling the potential of chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer in eye disease treatments.},
journal = {International journal of biological macromolecules},
volume = {273},
number = {Pt 2},
pages = {132700},
doi = {10.1016/j.ijbiomac.2024.132700},
pmid = {38879998},
issn = {1879-0003},
mesh = {Humans ; *Chitosan/chemistry/therapeutic use ; *Hyaluronic Acid/chemistry/therapeutic use ; *Cellulose/chemistry/therapeutic use ; *Poloxamer/chemistry ; *Eye Diseases/drug therapy ; *Cyclodextrins/chemistry/therapeutic use ; Drug Delivery Systems ; Animals ; Drug Carriers/chemistry ; Ophthalmic Solutions/chemistry/therapeutic use ; Administration, Ophthalmic ; },
abstract = {Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery.},
}
@article {pmid38878897,
year = {2024},
author = {Romano, F and Vingopoulos, F and Yuan, M and Ding, X and Garcia, M and Ploumi, I and Rodriguez, J and Garg, I and Tracy, JH and Bannerman, A and Choi, H and Stettler, I and Bennett, C and Overbey, KM and Laìns, I and Kim, LA and Vavvas, DG and Husain, D and Miller, JW and Miller, JB},
title = {Decreased Macular Choriocapillaris Perfusion Correlates with Contrast Sensitivity Function in Dry Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {12},
pages = {1140-1150},
doi = {10.1016/j.oret.2024.06.005},
pmid = {38878897},
issn = {2468-6530},
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; *Choroid/blood supply/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Aged ; *Contrast Sensitivity/physiology ; *Visual Acuity ; *Fluorescein Angiography/methods ; *Fundus Oculi ; *Macula Lutea/diagnostic imaging/blood supply ; Geographic Atrophy/physiopathology/diagnosis ; Aged, 80 and over ; Regional Blood Flow/physiology ; Middle Aged ; },
abstract = {PURPOSE: To investigate the relationships between contrast sensitivity (CS), choriocapillaris perfusion, and other structural OCT biomarkers in dry age-related macular degeneration (AMD).<br><br>DESIGN: Cross-sectional, observational study.<br><br>PARTICIPANTS: One hundred AMD eyes (22 early, 52 intermediate, and 26 late) from 74 patients and 45 control eyes from 37 age-similar subjects.<br><br>METHODS: All participants had visual acuity (VA) assessment, quantitative CS function (qCSF) testing, macular OCT, and 6&#xa0;&#xd7; 6-mm swept-source OCT angiography scans on the same day. OCT volumes were analyzed for subretinal drusenoid deposits and hyporeflective drusen cores, and to measure thickness of the outer nuclear layer. OCT angiography scans were utilized to calculate drusen volume and inner choroid flow deficit percentage (IC-FD%), and to measure the area of choroidal hypertransmission defects (HTDs). Inner choroid flow deficit percentage was measured from a 16-&#x3bc;m thick choriocapillaris slab after compensation and binarization with Phansalkar's method. Generalized linear mixed-effects models were used to evaluate the associations between functional and structural variables.<br><br>MAIN OUTCOME MEASURES: To explore the associations between qCSF-measured CS, IC-FD%, and various AMD imaging biomarkers.<br><br>RESULTS: Age-related macular degeneration exhibited significantly reduced qCSF metrics eyes across all stages compared with controls. Univariate analysis revealed significant associations between various imaging biomarkers, reduced qCSF metrics, and VA in both groups. Multivariate analysis confirmed that higher IC-FD% in the central 5 mm was significantly associated with decreases in all qCSF metrics in AMD eyes (&#x3b2;&#xa0;=&#xa0;-0.74 to&#xa0;-0.25, all P < 0.05), but not with VA (P > 0.05). Outer nuclear layer thickness in the central 3 mm correlated with both VA (&#x3b2;&#xa0;= 2.85, P < 0.001) and several qCSF metrics (&#x3b2;&#xa0;= 0.01-0.90, all P < 0.05), especially in AMD eyes. Further, larger HTD areas were associated with decreased VA (&#x3b2;&#xa0;=&#xa0;-0.89, P < 0.001) and reduced CS at low-intermediate frequencies across AMD stages (&#x3b2;&#xa0;=&#xa0;-0.30 to&#xa0;-0.29, P < 0.001).<br><br>CONCLUSIONS: The significant association between IC-FD% in the central 5 mm and qCSF-measured CS reinforces the hypothesis that decreased macular choriocapillaris perfusion contributes to visual function changes in AMD, which are more pronounced in CS than in VA.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38878454,
year = {2024},
author = {Song, Y and Wei, D and Wang, Q and Guo, J and Zhu, Y and Shang, E and Duan, JA},
title = {Luteoloside mitigates premature age-related macular degeneration by suppressing p53-p21-Rb1 axis: Insights from transcriptomic analysis, serum metabolomics and gut microbiota analysis.},
journal = {Journal of pharmaceutical and biomedical analysis},
volume = {248},
number = {},
pages = {116296},
doi = {10.1016/j.jpba.2024.116296},
pmid = {38878454},
issn = {1873-264X},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Macular Degeneration/drug therapy/blood ; Male ; *Tumor Suppressor Protein p53/metabolism ; *Metabolomics/methods ; Disease Models, Animal ; Humans ; Mice, Inbred C57BL ; Gene Expression Profiling/methods ; Transcriptome/drug effects ; },
abstract = {Transcriptomics of dry age-related macular degeneration (AMD) patients with premature aging revealed the upregulated pathways involved in glycerolipid metabolism, tyrosine metabolism, and pentose and glucuronate interconversion. To investigate natural strategies for modulating these implicated pathways, we examined the impact and underlying mechanism of luteoloside on premature AMD using a stress-induced premature senescence (SIPS)-associated AMD animal model in middle-aged mice that mimicked the dysregulated pathways observed in dry AMD patients with premature aging. Luteoloside supplementation resulted in a significant reduction in serum levels of the pro-inflammatory cytokine IL-1β and lipofuscin, along with increased serum activity of the antioxidant enzyme superoxide dismutase (SOD) and elevated levels of pigment epithelium-derived factor (PEDF), and preserved retinal thickness and structure in AMD mice. Furthermore, luteoloside supplementation effectively reversed the abnormal serum levels of metabolites, particularly by reducing harmful lysophosphatidylcholine (LysoPC) and increasing beneficial 4-guanidinobutanoic acid. In addition to its impact on metabolites, luteoloside modulated the composition of gut microbiota, promoting the enrichment of beneficial bacterial populations, including Lactobacillus, while reducing the abundance of harmful bacterial populations, including Bacteroides. Overall, our findings highlight the potential of luteoloside supplementation in regulating the dysregulated intestinal microbiota and metabolites in premature AMD, thereby reducing ocular levels of senescence-associated secretory phenotype (SASP) factors through the suppression of the p53-p21-retinoblastoma protein 1 (Rb1) axis.},
}
@article {pmid38878130,
year = {2024},
author = {Lee, H and Huh, J and Kim, D and Lee, S and Lee, J and Lee, J and Kim, BC and Song, J},
title = {Analytical Characterization for Similarity Assessment Between an Aflibercept Biosimilar SB15 and Reference Product (Eylea[®]).},
journal = {Ophthalmology and therapy},
volume = {13},
number = {8},
pages = {2209-2225},
pmid = {38878130},
issn = {2193-8245},
abstract = {INTRODUCTION: SB15 is a proposed biosimilar product of reference aflibercept (Eylea[®]), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties.<br><br>METHODS: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted.<br><br>RESULTS: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept.<br><br>CONCLUSIONS: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15.},
}
@article {pmid38876307,
year = {2024},
author = {Goodrich, AC and LeClair, NP and Shillova, N and Morton, WD and Wittwer, AJ and Loyet, KM and Hannoush, RN},
title = {Reconstitution of the alternative pathway of the complement system enables rapid delineation of the mechanism of action of novel inhibitors.},
journal = {The Journal of biological chemistry},
volume = {300},
number = {7},
pages = {107467},
pmid = {38876307},
issn = {1083-351X},
mesh = {Humans ; *Complement Pathway, Alternative/drug effects ; Complement C3/metabolism/antagonists &amp; inhibitors ; Complement Inactivating Agents/pharmacology ; Complement C3b/metabolism ; },
abstract = {The complement system plays a critical role in the innate immune response, acting as a first line of defense against invading pathogens. However, dysregulation of the complement system is implicated in the pathogenesis of numerous diseases, ranging from Alzheimer's to age-related macular degeneration and rare blood disorders. As such, complement inhibitors have enormous potential to alleviate disease burden. While a few complement inhibitors are in clinical use, there is still a significant unmet medical need for the discovery and development of novel inhibitors to treat patients suffering from disorders of the complement system. A key hurdle in the development of complement inhibitors has been the determination of their mechanism of action. Progression along the complement cascade involves the formation of numerous multimeric protein complexes, creating the potential for inhibitors to act at multiple nodes in the pathway. This is especially true for molecules that target the central component C3 and its fragment C3b, which serve a dual role as a substrate for the C3 convertases and as a scaffolding protein in both the C3 and C5 convertases. Here, we report a step-by-step in vitro reconstitution of the complement alternative pathway using bio-layer interferometry. By physically uncoupling each step in the pathway, we were able to determine the kinetic signature of inhibitors that act at single steps in the pathway and delineate the full mechanism of action of known and novel C3 inhibitors. The method could have utility in drug discovery and further elucidating the biochemistry of the complement system.},
}
@article {pmid38876134,
year = {2024},
author = {Ying, GS and VanderBeek, BL},
title = {Radiotherapy for anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration.},
journal = {Lancet (London, England)},
volume = {404},
number = {10447},
pages = {4-5},
doi = {10.1016/S0140-6736(24)00915-2},
pmid = {38876134},
issn = {1474-547X},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Macular Degeneration/drug therapy/radiotherapy ; Intravitreal Injections ; Ranibizumab/administration &amp; dosage/therapeutic use ; Wet Macular Degeneration/drug therapy ; Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; },
}
@article {pmid38876132,
year = {2024},
author = {Jackson, TL and Desai, R and Wafa, HA and Wang, Y and Peacock, J and Peto, T and Chakravarthy, U and Dakin, H and Wordsworth, S and Lewis, C and Clinch, P and Ramazzotto, L and Neffendorf, JE and Lee, CN and O'Sullivan, JM and Reeves, BC and , },
title = {Stereotactic radiotherapy for neovascular age-related macular degeneration (STAR): a pivotal, randomised, double-masked, sham-controlled device trial.},
journal = {Lancet (London, England)},
volume = {404},
number = {10447},
pages = {44-54},
doi = {10.1016/S0140-6736(24)00687-1},
pmid = {38876132},
issn = {1474-547X},
support = {/MRC_/Medical Research Council/United Kingdom ; //NIHR/ ; },
mesh = {Humans ; Male ; Double-Blind Method ; Female ; Aged ; *Visual Acuity ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Radiosurgery/methods ; *Intravitreal Injections ; Middle Aged ; Macular Degeneration ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; },
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential. STAR aimed to assess whether stereotactic radiotherapy (SRT) reduces the number of anti-VEGF injections required, without sacrificing visual acuity.<br><br>METHODS: This pivotal, randomised, double-masked, sham-controlled trial enrolled participants with pretreated chronic active nAMD from 30 UK hospitals. Participants were randomly allocated in a 2:1 ratio to 16-Gray (Gy) SRT delivered using a robotically controlled device or sham SRT, stratified by treatment centre. Eligible participants were aged 50 years or older and had chronic active nAMD, with at least three previous anti-VEGF injections, including at least one in the last 4 months. Participants and all trial and image reading centre staff were masked to treatment allocation, except one unmasked statistician. The primary outcome was the number of intravitreal ranibizumab injections required over 2 years, tested for superiority (fewer injections). The main secondary outcome was Early Treatment Diabetic Retinopathy Study visual acuity at two years, tested for non-inferiority (five-letter margin). The primary analysis used the intention-to-treat principle, and safety was analysed per-protocol on participants with available data. The study is registered with ClinicalTrials.gov (NCT02243878) and is closed for recruitment.<br><br>FINDINGS: 411 participants enrolled between Jan 1, 2015, and Dec 27, 2019, and 274 were randomly allocated to the 16-Gy SRT group and 137 to the sham SRT group. 240 (58%) of all participants were female, and 171 (42%) of all participants were male. 241 participants in the 16-Gy SRT group and 118 participants in the sham group were included in the final analysis, and 409 patients were treated and formed the safety population, of whom two patients allocated to sham treatment erroneously received 16-Gy SRT. The SRT group received a mean of 10&#xb7;7 injections (SD 6&#xb7;3) over 2 years versus 13&#xb7;3 injections (5&#xb7;8) with sham, a reduction of 2&#xb7;9 injections after adjusting for treatment centre (95% CI -4&#xb7;2 to -1&#xb7;6, p<0&#xb7;0001). The SRT group best-corrected visual acuity change was non-inferior to sham (adjusted mean letter loss difference between groups, -1&#xb7;7 letters [95% CI -4&#xb7;2 to 0&#xb7;8]). Adverse event rates were similar across groups, but reading centre-detected microvascular abnormalities occurred in 77 SRT-treated eyes (35%) and 13 (12%) sham-treated eyes. Overall, eyes with microvascular abnormalities tended to have better best-corrected visual acuity than those without. Fewer ranibizumab injections offset the cost of SRT, saving a mean of &#xa3;565 per participant (95% CI -332 to 1483).<br><br>INTERPRETATION: SRT can reduce ranibizumab treatment burden without compromising vision.<br><br>FUNDING: Medical Research Council and National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.},
}
@article {pmid38875582,
year = {2024},
author = {Young, JA and Chang, CW and Scales, CW and Menon, SV and Holy, CE and Blackie, CA},
title = {Machine Learning Methods Using Artificial Intelligence Deployed on Electronic Health Record Data for Identification and Referral of At-Risk Patients From Primary Care Physicians to Eye Care Specialists: Retrospective, Case-Controlled Study.},
journal = {JMIR AI},
volume = {3},
number = {},
pages = {e48295},
pmid = {38875582},
issn = {2817-1705},
abstract = {BACKGROUND: Identification and referral of at-risk patients from primary care practitioners (PCPs) to eye care professionals remain a challenge. Approximately 1.9 million Americans suffer from vision loss as a result of undiagnosed or untreated ophthalmic conditions. In ophthalmology, artificial intelligence (AI) is used to predict glaucoma progression, recognize diabetic retinopathy (DR), and classify ocular tumors; however, AI has not yet been used to triage primary care patients for ophthalmology referral.<br><br>OBJECTIVE: This study aimed to build and compare machine learning (ML) methods, applicable to electronic health records (EHRs) of PCPs, capable of triaging patients for referral to eye care specialists.<br><br>METHODS: Accessing the Optum deidentified EHR data set, 743,039 patients with 5 leading vision conditions (age-related macular degeneration [AMD], visually significant cataract, DR, glaucoma, or ocular surface disease [OSD]) were exact-matched on age and gender to 743,039 controls without eye conditions. Between 142 and 182 non-ophthalmic parameters per patient were input into 5 ML methods: generalized linear model, L1-regularized logistic regression, random forest, Extreme Gradient Boosting (XGBoost), and J48 decision tree. Model performance was compared for each pathology to select the most predictive algorithm. The area under the curve (AUC) was assessed for all algorithms for each outcome.<br><br>RESULTS: XGBoost demonstrated the best performance, showing, respectively, a prediction accuracy and an AUC of 78.6% (95% CI 78.3%-78.9%) and 0.878 for visually significant cataract, 77.4% (95% CI 76.7%-78.1%) and 0.858 for exudative AMD, 79.2% (95% CI 78.8%-79.6%) and 0.879 for nonexudative AMD, 72.2% (95% CI 69.9%-74.5%) and 0.803 for OSD requiring medication, 70.8% (95% CI 70.5%-71.1%) and 0.785 for glaucoma, 85.0% (95% CI 84.2%-85.8%) and 0.924 for type 1 nonproliferative diabetic retinopathy (NPDR), 82.2% (95% CI 80.4%-84.0%) and 0.911 for type 1 proliferative diabetic retinopathy (PDR), 81.3% (95% CI 81.0%-81.6%) and 0.891 for type 2 NPDR, and 82.1% (95% CI 81.3%-82.9%) and 0.900 for type 2 PDR.<br><br>CONCLUSIONS: The 5 ML methods deployed were able to successfully identify patients with elevated odds ratios (ORs), thus capable of patient triage, for ocular pathology ranging from 2.4 (95% CI 2.4-2.5) for glaucoma to 5.7 (95% CI 5.0-6.4) for type 1 NPDR, with an average OR of 3.9. The application of these models could enable PCPs to better identify and triage patients at risk for treatable ophthalmic pathology. Early identification of patients with unrecognized sight-threatening conditions may lead to earlier treatment and a reduced economic burden. More importantly, such triage may improve patients' lives.},
}
@article {pmid38875039,
year = {2024},
author = {Lee, CS and Ferguson, AN and Gibbons, LE and Walker, R and Su, YR and Krakauer, C and Brush, M and Kam, J and Larson, EB and Arterburn, DE and Crane, PK and , },
title = {Eye Adult Changes in Thought (Eye ACT) Study: Design and Report on the Inaugural Cohort.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {100},
number = {1},
pages = {309-320},
pmid = {38875039},
issn = {1875-8908},
support = {OT2 OD032644/OD/NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; U01 AG006781/AG/NIA NIH HHS/United States ; U19 AG066567/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; Cohort Studies ; *Alzheimer Disease/diagnostic imaging ; Retina/diagnostic imaging ; Aged, 80 and over ; Vision Disorders ; Middle Aged ; Dementia/diagnostic imaging ; Tomography, Optical Coherence ; Research Design ; },
abstract = {BACKGROUND: Conflicting research on retinal biomarkers of Alzheimer's disease and related dementias (AD/ADRD) is likely related to limited sample sizes, study design, and protocol differences.<br><br>OBJECTIVE: The prospective Eye Adult Changes in Thought (Eye ACT) seeks to address these gaps.<br><br>METHODS: Eye ACT participants are recruited from ACT, an ongoing cohort of dementia-free, older adults followed biennially until AD/ADRD, and undergo visual function and retinal imaging assessment either in clinic or at home.<br><br>RESULTS: 330 participants were recruited as of 03/2023. Compared to ACT participants not in Eye ACT (N&#x200a;=&#x200a;1868), Eye ACT participants (N&#x200a;=&#x200a;330) are younger (mean age: 70.3 versus 71.2, p&#x200a;=&#x200a;0.014), newer to ACT (median ACT visits since baseline: 3 versus 4, p&#x200a;<&#x200a;0.001), have more years of education (17.7 versus 16.2, p&#x200a;<&#x200a;0.001) and had lower rates of visual impairment (12% versus 22%, p&#x200a;<&#x200a;0.001). Compared to those seen in clinic (N&#x200a;=&#x200a;300), Eye ACT participants seen at home (N&#x200a;=&#x200a;30) are older (77.2 versus 74.9, p&#x200a;=&#x200a;0.015), more frequently female (60% versus 49%, p&#x200a;=&#x200a;0.026), and have significantly worse visual acuity (71.1 versus 78.9 Early Treatment Diabetic Retinopathy Study letters, p&#x200a;<&#x200a;0.001) and contrast sensitivity (-1.9 versus -2.1 mean log units at 3 cycles per degree, p&#x200a;=&#x200a;0.002). Cognitive scores and retinal imaging measurements are similar between the two groups.<br><br>CONCLUSIONS: Participants assessed at home had significantly worse visual function than those seen in clinic. By including these participants, Eye ACT provides a unique longitudinal cohort for evaluating potential retinal biomarkers of dementia.},
}
@article {pmid38874975,
year = {2024},
author = {Aresta, G and Araujo, T and Reiter, GS and Mai, J and Riedl, S and Grechenig, C and Guymer, RH and Wu, Z and Schmidt-Erfurth, U and Bogunovic, H},
title = {Deep Neural Networks for Automated Outer Plexiform Layer Subsidence Detection on Retinal OCT of Patients With Intermediate AMD.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {6},
pages = {7},
pmid = {38874975},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Aged ; Female ; *Neural Networks, Computer ; Male ; *Macular Degeneration/diagnostic imaging/diagnosis/pathology ; Geographic Atrophy/diagnostic imaging/diagnosis ; Disease Progression ; Retina/diagnostic imaging/pathology ; Middle Aged ; Aged, 80 and over ; },
abstract = {PURPOSE: The subsidence of the outer plexiform layer (OPL) is an important imaging biomarker on optical coherence tomography (OCT) associated with early outer retinal atrophy and a risk factor for progression to geographic atrophy in patients with intermediate age-related macular degeneration (AMD). Deep neural networks (DNNs) for OCT can support automated detection and localization of this biomarker.<br><br>METHODS: The method predicts potential OPL subsidence locations on retinal OCTs. A detection module (DM) infers bounding boxes around subsidences with a likelihood score, and a classification module (CM) assesses subsidence presence at the B-scan level. Overlapping boxes between B-scans are combined and scored by the product of the DM and CM predictions. The volume-wise score is the maximum prediction across all B-scans. One development and one independent external data set were used with 140 and 26 patients with AMD, respectively.<br><br>RESULTS: The system detected more than 85% of OPL subsidences with less than one false-positive (FP)/scan. The average area under the curve was 0.94 &#xb1; 0.03 for volume-level detection. Similar or better performance was achieved on the independent external data set.<br><br>CONCLUSIONS: DNN systems can efficiently perform automated retinal layer subsidence detection in retinal OCT images. In particular, the proposed DNN system detects OPL subsidence with high sensitivity and a very limited number of FP detections.<br><br>TRANSLATIONAL RELEVANCE: DNNs enable objective identification of early signs associated with high risk of progression to the atrophic late stage of AMD, ideally suited for screening and assessing the efficacy of the interventions aiming to slow disease progression.},
}
@article {pmid38874963,
year = {2024},
author = {Connolly, E and Knight, SP and Duggan, E and Scarlett, S and Newman, L and Cahill, M and Kenny, RA and Doyle, SL and Romero-Ortuno, R},
title = {Cardiovascular Autonomic Function and Progression of Age-Related Macular Degeneration in The Irish Longitudinal Study of Ageing (TILDA).},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {6},
pages = {24},
pmid = {38874963},
issn = {1552-5783},
mesh = {Humans ; Male ; Female ; *Disease Progression ; Aged ; *Macular Degeneration/physiopathology ; Ireland/epidemiology ; *Heart Rate/physiology ; *Aging/physiology ; *Blood Pressure/physiology ; Longitudinal Studies ; Autonomic Nervous System/physiopathology ; Aged, 80 and over ; Hemodynamics/physiology ; Middle Aged ; Risk Factors ; },
abstract = {PURPOSE: To examine if changes in hemodynamic measures during an orthostatic challenge were associated with progression of age-related macular degeneration (AMD) over a 4-year period in The Irish Longitudinal Study on Ageing.<br><br>METHODS: Participants with AMD who underwent an active stand (AS) test at wave 1 (2009/2010) and retinal photographs at both wave 1 and wave 3 (2014/2015) were included (N = 159: 121 with no AMD progression and 38 with progression). Beat-to-beat hemodynamic data were non-invasively collected using a Finometer MIDI device during the AS at wave 1, recording systolic blood pressure (sBP), diastolic blood pressure (dBP), mean arterial pressure (MAP), and heart rate. Cardiac output, stroke volume, and total peripheral resistance (TPR) were derived from these measures. Baseline characteristics were compared between groups with and without AMD progression. Mixed-effects linear regression models were used to assess the association between changes in hemodynamic parameters during the AS and AMD progression, controlling for known AMD-associated risk factors.<br><br>RESULTS: At baseline, increasing age and lower dBP were significantly associated with AMD progression. Mixed-effects models for the period between standing and 10 seconds post-stand revealed significant associations with AMD progression with a steeper drop in dBP and a slower drop in TPR. Between 10 and 20 seconds post-stand, AMD progression was significantly associated with less pronounced reduction in heart rate.<br><br>CONCLUSIONS: These observational data suggest that impaired hemodynamic responses within the first 20 seconds of orthostasis may be associated with the progression of AMD.},
}
@article {pmid38874663,
year = {2024},
author = {Lulli, M and Tartaro, R and Papucci, L and Magnelli, L and Kaur, IP and Caporossi, T and Rizzo, S and Mannini, A and Giansanti, F and Schiavone, N},
title = {Effects of a human amniotic membrane extract on ARPE-19 cells.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {746},
pmid = {38874663},
issn = {1573-4978},
mesh = {Humans ; *Amnion/cytology/drug effects ; Cell Line ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; *Cell Survival/drug effects ; *Apoptosis/drug effects ; *Oxidative Stress/drug effects ; *Cell Proliferation/drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Tissue Extracts/pharmacology ; },
abstract = {BACKGROUND: Human Amniotic Membrane (hAM) is endowed with several biological activities and might be considered an optimal tool in surgical treatment for different ophthalmic pathologies. We pioneered the surgical use of hAM to treat retinal pathologies such as macular holes, tears, and retinal detachments, and to overcome photoreceptor damage in age-related macular degeneration. Although hAM contributed to improved outcomes, the mechanisms of its effects are not yet fully understood. The characterization and explanation of the effects of hAM would allow the adoption of this new natural product in different retinal pathologies, operative contexts, and hAM formulations. At this end, we studied the properties of a hAM extract (hAME) on the ARPE-19 cells.<br><br>METHODS AND RESULTS: A non-denaturing sonication-based technique was developed to obtain a suitable hAME. Viability, proliferation, apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) were studied in hAME-treated ARPE-19 cells. The hAME was able to increase ARPE-19 cell viability even in the presence of oxidative stress (H2O2, TBHP). Moreover, hAME prevented the expression of EMT features, such as EMT-related proteins, fibrotic foci formation, and migration induced by different cytokines.<br><br>CONCLUSIONS: Our results demonstrate that the hAME retains most of the properties observed in the whole tissue by others. The hAME, other than providing a manageable research tool, could represent a cost-effective and abundant drug to treat retinal pathologies in the future.},
}
@article {pmid38872627,
year = {2024},
author = {Hou, Y and Liu, Q and Xiao, Z and Li, Y and Tian, X and Wang, Z},
title = {Association between chronic kidney disease and age-related macular degeneration: a Mendelian randomization study.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1399666},
pmid = {38872627},
issn = {1663-4365},
abstract = {PURPOSE: Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent.<br><br>METHODS: Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers.<br><br>RESULTS: IVW results showed that CKD, eGFR were not associated with any type of AMD (p&#x2009;>&#x2009;0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, p&#x2009;=&#x2009;0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, p&#x2009;=&#x2009;0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, p&#x2009;=&#x2009;4.87&#x2009;&#xd7;&#x2009;10[-8]), IgAN (OR: 1.373, 95% CI: 1.097-1.719, p&#x2009;=&#x2009;0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, p&#x2009;=&#x2009;0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, p&#x2009;=&#x2009;1.57&#x2009;&#xd7;&#x2009;10[-4]) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, p&#x2009;=&#x2009;7.55&#x2009;&#xd7;&#x2009;10[-4]) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, p&#x2009;=&#x2009;7.56&#x2009;&#xd7;&#x2009;10[-4]) and MN (OR: 1.071, 95% CI: 1.040-1.103, p&#x2009;=&#x2009;5.48&#x2009;&#xd7;&#x2009;10[-6]).<br><br>CONCLUSION: This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.},
}
@article {pmid38869976,
year = {2024},
author = {Wheeler, S and Mahmoudzadeh, R and Randolph, J},
title = {Treatment for dry age-related macular degeneration: where we stand in 2024.},
journal = {Current opinion in ophthalmology},
volume = {35},
number = {5},
pages = {359-364},
doi = {10.1097/ICU.0000000000001064},
pmid = {38869976},
issn = {1531-7021},
mesh = {Humans ; *Geographic Atrophy/therapy ; *Genetic Therapy ; Stem Cell Transplantation ; Angiogenesis Inhibitors/therapeutic use ; Laser Therapy/methods ; Macular Degeneration/therapy ; },
abstract = {PURPOSE OF REVIEW: This review highlights treatment options, both under investigation and currently available, for the treatment of dry age-related macular degeneration (AMD). An update on current clinical studies for dry AMD has been summarized.<br><br>RECENT FINDINGS: Advanced dry AMD, characterized by geographic atrophy (GA), is a leading cause of blindness in the developed world, though prior to 2023 there was no approved treatment. There are now two approved treatments in the United States for GA. Additionally, there are several studies and trials to investigate therapeutic potential and effects of therapies for earlier intervention in dry AMD. Approaches to therapy include inhibiting the complement system, utilizing gene therapy, stem cell therapy, laser therapy, and surgical implants.<br><br>SUMMARY: While there has been notable prior advancement in the treatment for neovascular or wet AMD, for the first time there are Food and Drug Administration (FDA) approved treatments for GA. Clinical studies have shown promise for additional methods for managing dry AMD both medically and surgically.},
}
@article {pmid38867671,
year = {2024},
author = {Zou, M and Chen, A and Liu, Z and Jin, L and Zheng, D and Congdon, N and Jin, G},
title = {The burden, causes, and determinants of blindness and vision impairment in Asia: An analysis of the Global Burden of Disease Study.},
journal = {Journal of global health},
volume = {14},
number = {},
pages = {04100},
pmid = {38867671},
issn = {2047-2986},
mesh = {Humans ; *Blindness/epidemiology/etiology ; *Global Burden of Disease ; Female ; Male ; Aged ; Middle Aged ; Asia/epidemiology ; *Disability-Adjusted Life Years ; Adult ; Aged, 80 and over ; Prevalence ; Young Adult ; Adolescent ; Child ; Child, Preschool ; Infant ; Cataract/epidemiology/complications ; Vision, Low/epidemiology ; Refractive Errors/epidemiology/complications ; },
abstract = {BACKGROUND: Asia accounts for more than half of the world's population and carries a substantial proportion of the global burden of blindness and vision impairment. Characterising this burden, as well as its causes and determinants, could help with devising targeted interventions for reducing the occurrence of blindness and visual impairment.<br><br>METHODS: Using the Global Burden of Disease Study 2019 database, we retrieved data on the number of disability-adjusted life years (DALYs); crude and age-standardised rates; and the prevalence (with 95% uncertainty intervals (95%UIs)) of blindness and vision loss due to six causes (age-related macular degeneration, cataracts, glaucoma, near-vision impairment, refractive error, and other vision loss) for Asian countries for the period between 1990 and 2019. We defined DALYs as the sum of the years lost due to disability and years of life lost, and calculated age-standardised figures for the number of DALYs and prevalence by adjusting for population size and age structure. We then evaluated the time trend of the disease burden and conducted subgroup analyses by gender, age, geographic locations, and socio-demographic index (SDI).<br><br>RESULTS: In 2019, the DALYs and prevalence of blindness and vision loss had risen by 90.1% and 116% compared with 1990, reaching 15.84 million DALYs (95% UI&#x2009;=&#x2009;15.83, 15.85) and 506.71 million cases (95% UI&#x2009;=&#x2009;506.68, 506.74). Meanwhile, the age-standardised rate of DALYs decreased from 1990 to 2019. Cataracts, refractive error, and near vision impairment were the three most common causes. South Asia had the heaviest regional disease burden (age-standardised rate of DALYs&#x2009;=&#x2009;517 per 100&#x2009;000 population; 95% UI&#x2009;=&#x2009;512, 521). Moreover, the burden due to cataracts ranked high in most Asian populations. Being a woman; being older; and having a lower national SDI were factors associated with a greater vision loss burden.<br><br>CONCLUSIONS: The burden due to vision loss remains high in Asian populations. Cataracts, refractive error, and near vision loss were the primary causes of blindness and vision loss. Greater investment in ocular disease prevention and care by countries with lower socioeconomic status is needed, as well as specific strategies targeting cataract management, women and the elderly.},
}
@article {pmid38865606,
year = {2025},
author = {Choi, S and Kim, G and Pionke, JJ},
title = {The Sleep Health of Individuals with Visual Impairments: A Scoping Review.},
journal = {Ophthalmic epidemiology},
volume = {32},
number = {3},
pages = {259-277},
doi = {10.1080/09286586.2024.2361167},
pmid = {38865606},
issn = {1744-5086},
mesh = {Humans ; *Persons with Visual Disabilities/statistics &amp; numerical data ; Prevalence ; *Sleep/physiology ; *Sleep Quality ; *Sleep Wake Disorders/epidemiology/physiopathology/etiology ; *Vision Disorders/physiopathology/epidemiology/complications ; },
abstract = {PURPOSE: Amidst the global aging population and an increasing prevalence of visual impairment across all age groups, this study aims to investigate the current state of research on sleep health in visually impaired populations.<br><br>METHODS: A scoping review was conducted to synthesize the existing literature on sleep health and visual impairment. We employed conceptual mapping to identify key research topics, analyzing data from four databases: PubMed (n&#x2009;=&#x2009;290), CINAHL (n&#x2009;=&#x2009;81), Scopus (n&#x2009;=&#x2009;117), and PsycInfo (n&#x2009;=&#x2009;96). A total of 83 peer-reviewed articles, published from 1977 to August 2023, were included in the review.<br><br>RESULTS: Our analysis identified 11 distinct eye health conditions including blindness, glaucoma, diabetic retinopathy, low vision, cataract, retinitis pigmentosa, macular degeneration, optic neuropathy, visual field defects, ocular hypertension, and retinal vein occlusion. Additionally, 8 major sleep problems were recognized: abnormal sleep duration, daytime sleepiness, insomnia, Non-24-Hour Sleep Wake Disorder, sleep apnea, sleep disorders, sleep disturbances, and sleep disordered breathing. The dominant research themes were (1) poor sleep quality in individuals with visual impairments and ophthalmic diseases, (2) high prevalence of sleep issues in patients with ophthalmic diseases, (3) sleep apnea in patients with ophthalmic conditions, and (4) circadian rhythm disruptions in blind individuals.<br><br>CONCLUSION: This review highlights research gaps that, when addressed, could greatly enhance our comprehension of the interplay between visual impairment and sleep health. Bridging these gaps promises to lead to more holistic care strategies, potentially improving vision functioning and rehabilitation outcomes for individuals with visual impairments.},
}
@article {pmid38865272,
year = {2024},
author = {Chen, M and Wang, Y and Dalal, R and Du, J and Vollrath, D},
title = {Alternative oxidase blunts pseudohypoxia and photoreceptor degeneration due to RPE mitochondrial dysfunction.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {25},
pages = {e2402384121},
pmid = {38865272},
issn = {1091-6490},
support = {EY031324//HHS | National Institutes of Health (NIH)/ ; EY034002//HHS | National Institutes of Health (NIH)/ ; EY032462//HHS | National Institutes of Health (NIH)/ ; R01 EY031324/EY/NEI NIH HHS/United States ; R01 EY025790/EY/NEI NIH HHS/United States ; R01 EY032462/EY/NEI NIH HHS/United States ; R01 EY031720/EY/NEI NIH HHS/United States ; EY025790//HHS | National Institutes of Health (NIH)/ ; R01 EY034002/EY/NEI NIH HHS/United States ; R01 EY034364/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Mitochondria/metabolism ; Mice ; *Oxidoreductases/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Plant Proteins/metabolism/genetics ; Mitochondrial Proteins/metabolism/genetics ; Ciona intestinalis/metabolism ; Ubiquinone/metabolism/analogs &amp; derivatives ; Retinal Degeneration/metabolism/pathology/genetics ; Photoreceptor Cells, Vertebrate/metabolism/pathology ; },
abstract = {Loss of mitochondrial electron transport complex (ETC) function in the retinal pigment epithelium (RPE) in vivo results in RPE dedifferentiation and progressive photoreceptor degeneration, and has been implicated in the pathogenesis of age-related macular degeneration. Xenogenic expression of alternative oxidases in mammalian cells and tissues mitigates phenotypes arising from some mitochondrial electron transport defects, but can exacerbate others. We expressed an alternative oxidase from Ciona intestinalis (AOX) in ETC-deficient murine RPE in vivo to assess the retinal consequences of stimulating coenzyme Q oxidation and respiration without ATP generation. RPE-restricted expression of AOX in this context is surprisingly beneficial. This focused intervention mitigates RPE mTORC1 activation, dedifferentiation, hypertrophy, stress marker expression, pseudohypoxia, and aerobic glycolysis. These RPE cell autonomous changes are accompanied by increased glucose delivery to photoreceptors with attendant improvements in photoreceptor structure and function. RPE-restricted AOX expression normalizes accumulated levels of succinate and 2-hydroxyglutarate in ETC-deficient RPE, and counteracts deficiencies in numerous neural retinal metabolites. These features can be attributed to the activation of mitochondrial inner membrane flavoproteins such as succinate dehydrogenase and proline dehydrogenase, and alleviation of inhibition of 2-oxyglutarate-dependent dioxygenases such as prolyl hydroxylases and epigenetic modifiers. Our work underscores the importance to outer retinal health of coenzyme Q oxidation in the RPE and identifies a metabolic network critical for photoreceptor survival in the context of RPE mitochondrial dysfunction.},
}
@article {pmid38862935,
year = {2024},
author = {Yoon, CK and Lee, EK and Bae, K and Park, UC},
title = {Clinical features of primary and compound forms of wide macular posterior staphyloma in high myopia.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {246},
pmid = {38862935},
issn = {1471-2415},
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; *Myopia, Degenerative/complications/diagnosis ; Middle Aged ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; Aged ; *Sclera/pathology ; Retrospective Studies ; Adult ; Choroid/pathology/diagnostic imaging ; Scleral Diseases/diagnosis ; Macula Lutea/pathology/diagnostic imaging ; Dilatation, Pathologic ; },
abstract = {BACKGROUND: To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity.<br><br>METHODS: In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS.<br><br>RESULTS: A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P&#x2009;=&#x2009;0.001) and greater axial length (P&#x2009;<&#x2009;0.001) than those with primary WMPS. Compared to primary WMPS, compound WMPS had a higher grade of myopic macular degeneration (P&#x2009;<&#x2009;0.001) and a higher frequency of lamellar or full-thickness macular hole associated with myopic traction (21.5% vs. 10.4%; P&#x2009;=&#x2009;0.028) and active or scarred myopic choroidal neovascularization (33.8% vs. 20.1%; P&#x2009;=&#x2009;0.030). On swept-source optical coherence tomography, eyes with compound WMPS had significantly thinner choroid and sclera.<br><br>CONCLUSIONS: The compound form of WMPS had more severe myopic macular changes and worse visual prognosis compared to the primary form of WMPS, and these were associated with more structural deformation in the posterior eyeball. Compound WMPS should be considered as an advanced form of staphyloma.},
}
@article {pmid38861878,
year = {2024},
author = {Akpinar, MH and Sengur, A and Faust, O and Tong, L and Molinari, F and Acharya, UR},
title = {Artificial intelligence in retinal screening using OCT images: A review of the last decade (2013-2023).},
journal = {Computer methods and programs in biomedicine},
volume = {254},
number = {},
pages = {108253},
doi = {10.1016/j.cmpb.2024.108253},
pmid = {38861878},
issn = {1872-7565},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Artificial Intelligence ; *Retina/diagnostic imaging ; Retinal Diseases/diagnostic imaging ; Machine Learning ; Deep Learning ; },
abstract = {BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) has ushered in a transformative era in the domain of ophthalmology, offering non-invasive imaging with high resolution for ocular disease detection. OCT, which is frequently used in diagnosing fundamental ocular pathologies, such as glaucoma and age-related macular degeneration (AMD), plays an important role in the widespread adoption of this technology. Apart from glaucoma and AMD, we will also investigate pertinent pathologies, such as epiretinal membrane (ERM), macular hole (MH), macular dystrophy (MD), vitreomacular traction (VMT), diabetic maculopathy (DMP), cystoid macular edema (CME), central serous chorioretinopathy (CSC), diabetic macular edema (DME), diabetic retinopathy (DR), drusen, glaucomatous optic neuropathy (GON), neovascular AMD (nAMD), myopia macular degeneration (MMD) and choroidal neovascularization (CNV) diseases. This comprehensive review examines the role that OCT-derived images play in detecting, characterizing, and monitoring eye diseases.<br><br>METHOD: The 2020 PRISMA guideline was used to structure a systematic review of research on various eye conditions using machine learning (ML) or deep learning (DL) techniques. A thorough search across IEEE, PubMed, Web of Science, and Scopus databases yielded 1787 publications, of which 1136 remained after removing duplicates. Subsequent exclusion of conference papers, review papers, and non-open-access articles reduced the selection to 511 articles. Further scrutiny led to the exclusion of 435 more articles due to lower-quality indexing or irrelevance, resulting in 76 journal articles for the review.<br><br>RESULTS: During our investigation, we found that a major challenge for ML-based decision support is the abundance of features and the determination of their significance. In contrast, DL-based decision support is characterized by a plug-and-play nature rather than relying on a trial-and-error approach. Furthermore, we observed that pre-trained networks are practical and especially useful when working on complex images such as OCT. Consequently, pre-trained deep networks were frequently utilized for classification tasks. Currently, medical decision support aims to reduce the workload of ophthalmologists and retina specialists during routine tasks. In the future, it might be possible to create continuous learning systems that can predict ocular pathologies by identifying subtle changes in OCT images.},
}
@article {pmid38860119,
year = {2024},
author = {Yiu, G and Gulati, S and Higgins, V and Coak, E and Mascia, D and Kim, E and Spicer, G and Tabano, D},
title = {Factors Involved in Anti-VEGF Treatment Decisions for Neovascular Age-Related Macular Degeneration: Insights from Real-World Clinical Practice.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {1679-1690},
pmid = {38860119},
issn = {1177-5467},
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) agents are widely prescribed for the treatment of neovascular age-related macular degeneration (nAMD). Although studies have investigated patient choice of anti-VEGF agent, little is known regarding factors that influence physician preference of anti-VEGF agent for their patients.<br><br>OBJECTIVE: To describe physician rationale and challenges in prescribing anti-VEGF treatments for patients with nAMD.<br><br>METHODS: Data were drawn from the Adelphi Real World nAMD Disease Specific Programme&#x2122;, a cross-sectional survey with retrospective data capture of physicians and their patients with nAMD in the United States between October 2021 and May 2022. Physicians (n = 56) reported data for up to 13 consecutively consulting patients (n = 451), including current anti-VEGF treatments used, factors affecting physicians' choice of anti-VEGF agent and treatment strategy, and restrictions on specific agents.<br><br>RESULTS: Most physicians prefer employing a "treat-and-extend" treatment strategy, over "fixed interval" or "pro re nata" strategies. However, in routine clinical practice, "treat-and-extend" was reported for less than half of nAMD-diagnosed eyes. Top factors influencing physician choice of anti-VEGF agent and treatment strategy included maximizing clinical benefit (eg visual acuity gains and fluid control), patient convenience, and reducing out-of-pocket costs. However, physicians also reported facing substantial roadblocks in prescribing their choice of anti-VEGF agent, including restrictions on approved agents and gaps in insurance coverage. Persistent fluid was the most common physician-selected reason for switching a patient away from an anti-VEGF agent.<br><br>CONCLUSION: Physicians face barriers to prescribing their preferred anti-VEGF agents in real-world healthcare settings. Overcoming these challenges may improve treatment outcomes for patients with nAMD.},
}
@article {pmid38860019,
year = {2024},
author = {Zou, H and Sutherland, L and Geddie, B},
title = {Pigmentary retinal dystrophy associated with peroxisome biogenesis disorder-Zellweger syndrome spectrum.},
journal = {Oxford medical case reports},
volume = {2024},
number = {6},
pages = {omae067},
pmid = {38860019},
issn = {2053-8855},
abstract = {Pigmentary retinal dystrophy (PRD) is a group of inherited disorders involving the progressive degeneration of rod and cone photoreceptors and the retinal pigment epithelium (RPE), which can progress to pigmentary retinopathy (PR). We present a case of PRD in a female pediatric patient who has pathogenic variants in the PRPH2 and PEX1 genes. The patient has associated macular edema and secondary visual impairment. Treatment has included serial dexamethasone intravitreal implant injections and topical dorzolamide. The PEX1 gene mutation is associated with peroxisome biogenesis disorder-Zellweger syndrome spectrum (PBD-ZSS) and resulting retinal dystrophies. The PRPH2 mutation may play a role in macular edema and PRD, as it is implicated in macular degeneration, choroid defects, and photoreceptor dysfunction. In this case, we review multiple gene mutations playing potential etiologic roles for PRD and discuss care management.},
}
@article {pmid38857572,
year = {2024},
author = {Pandya, B and Mihalache, A and Hatamnejad, A and Grad, J and Popovic, MM and Wong, DTW},
title = {The Association between Retinal Thickness Fluctuations and Visual Outcomes under Anti-Vascular Endothelial Growth Factor Therapy: A Systematic Review and Meta-Analysis.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {4},
pages = {261-274},
pmid = {38857572},
issn = {1423-0267},
mesh = {Humans ; *Visual Acuity ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Intravitreal Injections ; *Retina/pathology ; *Tomography, Optical Coherence/methods ; Macular Edema/drug therapy/diagnosis/etiology ; Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Ranibizumab/administration &amp; dosage ; },
abstract = {INTRODUCTION: The objective of this study was to examine the association between retinal thickness (RT) fluctuations and best corrected visual acuity (BCVA) in eyes with neovascular AMD, macular edema secondary to RVO, and DME treated with anti-VEGF therapy.<br><br>METHODS: A systematic search of Ovid MEDLINE, EMBASE, and the Cochrane Library was performed from January 2006 to March 2024. Studies comparing visual or anatomic outcomes of patients treated with anti-VEGF therapy, stratified by magnitudes of RT fluctuation, were included. ROBINS-I and Cochrane RoB 2 tools were used to assess risk of bias, and certainty of evidence was evaluated with GRADE criteria. Meta-analysis was performed with a random-effects model. Primary outcomes were final BCVA and change in BCVA relative to baseline.<br><br>RESULTS: 15,725 articles were screened; 15 studies were identified in the systematic review and 5 studies were included in the meta-analysis. Final ETDRS VA was significantly worse in eyes with the highest level of RT fluctuation (weighted mean difference [WMD] = 7.86 letters; 95% CI, 4.97, 10.74; p < 0.00001; I2 = 81%; 3,136 eyes). RT at last observation was significantly greater in eyes with high RT fluctuations (WMD = -27.35 &#x3bc;m; 95% CI, -0.04, 54.75; p = 0.05; I2 = 88%; 962 eyes).<br><br>CONCLUSIONS: Final visual outcome is associated with magnitude of RT fluctuation over the course of therapy. It is unclear whether minimizing RT fluctuations would help optimize visual outcomes in patients treated with anti-VEGF therapy. These findings are limited by a small set of studies, risk of bias, and considerable heterogeneity.},
}
@article {pmid38857222,
year = {2024},
author = {Li, L and Zhang, M and Gu, M and Li, J and Li, Z and Zhang, R and Du, C and Lv, Y},
title = {The causal relationship between autoimmune diseases and age-related macular degeneration: A two-sample mendelian randomization study.},
journal = {PloS one},
volume = {19},
number = {6},
pages = {e0303170},
pmid = {38857222},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/genetics ; *Mendelian Randomization Analysis ; *Autoimmune Diseases/genetics/epidemiology ; *Genome-Wide Association Study ; *Polymorphism, Single Nucleotide ; Multiple Sclerosis/genetics ; Arthritis, Rheumatoid/genetics ; Male ; Diabetes Mellitus, Type 1/genetics ; Inflammatory Bowel Diseases/genetics ; Female ; },
abstract = {OBJECTIVE: The aim of this study is to investigate the potential causal relationship between autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and Type 1 diabetes, and age-related macular degeneration (AMD). By utilizing the two-sample Mendelian Randomization (MR) approach, we endeavor to address this complex medical issue.<br><br>METHODS: Genome-wide association study (GWAS) data for autoimmune diseases and AMD were obtained from the IEU Open GWAS database and the FinnGen consortium. A series of stringent SNP filtering steps was applied to ensure the reliability of the genetic instruments. MR analyses were conducted using the TwoSampleMR and MR-PRESSO packages in R. The inverse-variance weighted (IVW) method served as the primary analysis, complemented by multiple supplementary analyses and sensitivity tests.<br><br>RESULTS: Within the discovery sample, only a statistically significant inverse causal relationship between multiple sclerosis (MS) and AMD was observed (OR = 0.92, 95% CI: 0.88-0.97, P = 0.003). This finding was confirmed in the replication sample (OR = 0.85, 95% CI: 0.80-0.89, P = 3.32&#xd7;10-12). No statistically significant associations were detected between systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Type 1 diabetes and AMD.<br><br>CONCLUSION: Strong evidence is provided by this study to support the existence of an inverse causal relationship between multiple sclerosis and age-related macular degeneration. However, no causal evidence was found linking other autoimmune diseases with AMD. These findings not only offer novel insights into the potential etiological mechanisms underlying AMD but also suggest possible directions for future clinical interventions.},
}
@article {pmid38857040,
year = {2024},
author = {Scanlon, G and O'Shea, S and Amarandei, G and Butler, JS and O'Dwyer, V},
title = {Investigation of factors that may affect the foveal avascular zone: An optical coherence tomography angiography study.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {101},
number = {5},
pages = {276-283},
doi = {10.1097/OPX.0000000000002129},
pmid = {38857040},
issn = {1538-9235},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Adult ; Cross-Sectional Studies ; *Fovea Centralis/blood supply/diagnostic imaging ; Young Adult ; Adolescent ; *Fluorescein Angiography/methods ; *Retinal Vessels/diagnostic imaging ; Fundus Oculi ; Healthy Volunteers ; Body Mass Index ; },
abstract = {SIGNIFICANCE: An understanding of factors that affect the foveal avascular zone (FAZ) in healthy eyes may aid in the early identification of patients at risk of retinal pathology, thereby allowing better management and preventive measures to be implemented.<br><br>PURPOSE: The size and shape of the FAZ can change due to retinal diseases associated with oxidative stress, including diabetic retinopathy, glaucoma, and macular degeneration. This study aimed to assess the relationship, if any, between factors that may affect the superficial FAZ (i.e., vessel density, vessel perfusion, overweight/obesity) and possible links with macular pigment optical density in young, healthy participants.<br><br>METHODS: One hundred thirty-nine participants aged 18 to 35 years were recruited to this cross-sectional study. The superficial FAZ area, foveal vascularity, and central macular thickness (CMT) were assessed using the Cirrus 5000. Health parameters, body mass index, trunk fat %, and macular pigment were analyzed to determine possible associations with the superficial FAZ.<br><br>RESULTS: Mean FAZ area was 0.23 &#xb1; 0.08 mm2. Females had a significantly larger mean FAZ area than males (p=0.002). The FAZ area was positively correlated with body mass index (Pearson's r = 0.189, p=0.026). Significant correlates of the FAZ area in the multivariate model included vessel perfusion (central), CMT, and trunk fat %, collectively explaining 65.1% of the overall variability.<br><br>CONCLUSIONS: Study findings suggest that reduced vessel perfusion, thinner CMT, and higher trunk fat % are plausible predictors of a larger FAZ area in healthy Caucasian adults. Low macular pigment optical density was, however, not associated with increased FAZ size in young healthy eyes. Noninvasive optical coherence tomography angiography testing, in association with these predictors, may aid in the early detection and monitoring of retinal diseases associated with oxidative stress.},
}
@article {pmid38856728,
year = {2024},
author = {Chen, X and Wang, X and Li, X},
title = {Intra-Ocular Inflammation and Occlusive Retinal Vasculitis Following Intravitreal Injections of Faricimab: A Case Report.},
journal = {Ocular immunology and inflammation},
volume = {32},
number = {10},
pages = {2544-2547},
doi = {10.1080/09273948.2024.2361834},
pmid = {38856728},
issn = {1744-5078},
mesh = {Humans ; Male ; *Intravitreal Injections ; Aged ; *Tomography, Optical Coherence ; *Fluorescein Angiography ; *Retinal Vasculitis/chemically induced/diagnosis ; Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Angiopoietin-2 ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; },
abstract = {PURPOSE: Faricimab is a bispecific antibody that inhibits angiopoietin-2 and vascular endothelial growth factor-A action and has been approved for the treatment of neovascular age-related macular degeneration and diabetic macular edema. Clinical trials have demonstrated its favorable safety profile. This report presents a case of intra-ocular inflammation and occlusive retinal vasculitis following a second intravitreal injection of faricimab.<br><br>METHODS: A single case report was obtained from a tertiary referral center.<br><br>RESULTS: A 73-year-old Asian man diagnosed with polypoidal choroidal vasculopathy presented with decreased vision in the left eye (OS) 2&#x2009;weeks after the second faricimab administration. In the fourth week after the second faricimab injection, swept-source optical coherence tomography (OCT) revealed hyperreflective dots in the vitreous cavity, indicating vitreous cells. Color fundus photography showed new-onset perivenular hemorrhages and pallor of the inferonasal retina OS, of which OCT revealed retinal inner layer thickening, suggestive of retinal arteriolar occlusions. Retinal fluorescein angiography revealed delayed filling of the inferior temporal vein. The patient was diagnosed with intraocular inflammation and occlusive retinal vasculitis OS associated with repeated intravitreal faricimab administrations. Intravitreal dexamethasone implant was used instead of faricimab at this visit.<br><br>CONCLUSIONS: The findings of this case hint towards the potential risk of retinal occlusive events associated with intravitreal faricimab injections.},
}
@article {pmid38856212,
year = {2024},
author = {Hubal, A and Pfaff, A and Vos, S and Upadhyay, M and Bonilha, V and Subauste, CS},
title = {A Simplified Method for Isolation and Culture of Retinal Pigment Epithelial Cells from Adult Mice.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {207},
pages = {},
pmid = {38856212},
issn = {1940-087X},
support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 EY019250/EY/NEI NIH HHS/United States ; T32 AI089474/AI/NIAID NIH HHS/United States ; R01 EY018341/EY/NEI NIH HHS/United States ; F31 EY035156/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/cytology ; *Mice, Inbred C57BL ; Cytological Techniques/methods ; Cell Culture Techniques/methods ; Epithelial Cells/cytology ; },
abstract = {Retinal pigment epithelial cells (RPE) are critical for the proper function of the retina. RPE dysfunction is involved in the pathogenesis of important retinal diseases, such as age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. We present a streamlined approach for the isolation of RPE from murine adult eyes. In contrast to previously reported methods, this approach enables the isolation and culture of highly pure RPE from adult mice. This simple and fast method does not require extensive technical skill and is achievable with basic scientific tools and reagents. Primary RPE are isolated from C57BL/6 background mice aged 3- to 14-weeks by enucleation of the eye followed by the removal of the anterior segment. Enzymatic trypsinization and centrifugation are used to dissociate and isolate the RPE from the eyecup. In conclusion, this approach offers a quick and effective protocol for the utilization of RPE in the study of retinal function and disease.},
}
@article {pmid38856116,
year = {2024},
author = {Alshaikh, RA and Salah El Din, RA and Zaki, RGE and Waeber, C and Ryan, KB},
title = {In Vivo Ocular Pharmacokinetics and Toxicity of Siponimod in Albino Rabbits.},
journal = {Molecular pharmaceutics},
volume = {21},
number = {7},
pages = {3310-3320},
pmid = {38856116},
issn = {1543-8392},
mesh = {Animals ; Rabbits ; *Azetidines/pharmacokinetics/administration &amp; dosage ; *Intravitreal Injections ; Half-Life ; Vitreous Body/drug effects/metabolism ; Male ; Retina/drug effects/metabolism ; Eye/drug effects/metabolism ; Diabetic Retinopathy/drug therapy ; Angiogenesis Inhibitors/pharmacokinetics/administration &amp; dosage/toxicity ; Solubility ; Macular Degeneration/drug therapy ; Benzyl Compounds ; },
abstract = {Siponimod is a promising agent for the inhibition of ocular neovascularization in diabetic retinopathy and age-related macular degeneration. Siponimod's development for ophthalmological application is hindered by the limited information available on the drug's solubility, stability, ocular pharmacokinetics (PK), and toxicity in vivo. In this study, we investigated the aqueous stability of siponimod under stress conditions (up to 60 °C) and its degradation behavior in solution. Additionally, siponimod's ocular PK and toxicity were investigated using intravitreal injection of two different doses (either 1300 or 6500 ng) in an albino rabbit model. Siponimod concentration was quantified in the extracted vitreous, and the PK parameters were calculated. The drug half-life after administration of the low and high doses was 2.8 and 3.9 h, respectively. The data obtained in vivo was used to test the ability of published in silico models to predict siponimod's PK accurately. Two models that correlated siponimod's molecular descriptors with its elimination from the vitreous closely predicted the half-life. Furthermore, 24 h and 7 days after intravitreal injections, the retinas showed no signs of toxicity. This study provides important information necessary for the formulation and development of siponimod for ophthalmologic applications. The short half-life of siponimod necessitates the development of a sustained drug delivery system to maintain therapeutic concentrations over an extended period, while the lack of short-term ocular toxicity observed in the retinas of siponimod-treated rabbits supports possible clinical use.},
}
@article {pmid38852887,
year = {2024},
author = {Hallam, TM and Andreadi, A and Sharp, SJ and Brocklebank, V and Gardenal, E and Dreismann, A and , and Lotery, AJ and Marchbank, KJ and Harris, CL and Jones, AV and Kavanagh, D},
title = {Comprehensive functional characterization of complement factor I rare variant genotypes identified in the SCOPE geographic atrophy cohort.},
journal = {The Journal of biological chemistry},
volume = {300},
number = {7},
pages = {107452},
pmid = {38852887},
issn = {1083-351X},
support = {/WT_/Wellcome Trust/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Complement Factor I/genetics/metabolism ; *Geographic Atrophy/genetics/blood/metabolism ; *Genotype ; Female ; Male ; *Complement C3b/metabolism/genetics ; Aged ; Cohort Studies ; Macular Degeneration/genetics/metabolism ; Middle Aged ; },
abstract = {Rare variants (RVs) in the gene encoding the regulatory enzyme complement factor I (CFI; FI) that reduce protein function or levels increase age-related macular degeneration risk. A total of 3357 subjects underwent screening in the SCOPE natural history study for geographic atrophy secondary to age-related macular degeneration, including CFI sequencing and serum FI measurement. Eleven CFI RV genotypes that were challenging to categorize as type I (low serum level) or type II (normal serum level, reduced enzymatic function) were characterized in the context of pure FI protein in C3b and C4b fluid phase cleavage assays and a novel bead-based functional assay (BBFA) of C3b cleavage. Four variants predicted or previously characterized as benign were analyzed by BBFA for comparison. In all, three variants (W51S, C67R, and I370T) resulted in low expression. Furthermore, four variants (P64L, R339Q, G527V, and P528T) were identified as being highly deleterious with IC50s for C3b breakdown >1 log increased versus the WT protein, while two variants (K476E and R474Q) were ∼1 log reduced in function. Meanwhile, six variants (P50A, T203I, K441R, E548Q, P553S, and S570T) had IC50s similar to WT. Odds ratios and BBFA IC50s were positively correlated (r = 0.76, p < 0.01), while odds ratios versus combined annotation dependent depletion (CADD) scores were not (r = 0.43, p = 0.16). Overall, 15 CFI RVs were functionally characterized which may aid future patient stratification for complement-targeted therapies. Pure protein in vitro analysis remains the gold standard for determining the functional consequence of CFI RVs.},
}
@article {pmid38848872,
year = {2024},
author = {Arrigo, A and Aragona, E and Battaglia Parodi, M and Bandello, F},
title = {Quantitative Multimodal Imaging Characterization of Intraretinal Cysts versus Degenerative Pseudocysts in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {12},
pages = {1118-1126},
doi = {10.1016/j.oret.2024.05.019},
pmid = {38848872},
issn = {2468-6530},
mesh = {Humans ; Male ; *Multimodal Imaging ; Female ; Cross-Sectional Studies ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Wet Macular Degeneration/diagnosis ; *Cysts/diagnosis ; Aged, 80 and over ; *Visual Acuity ; *Fundus Oculi ; Aged ; Subretinal Fluid ; },
abstract = {OBJECTIVE: To differentiate intraretinal fluid (IRF) cysts from degenerative pseudocysts in neovascular age-related macular degeneration (AMD) by quantitative multimodal imaging.<br><br>DESIGN: Observational, cross-sectional.<br><br>PARTICIPANTS: Patients affected by macular neovascularization secondary to AMD.<br><br>METHODS: All patients were analyzed by OCT, OCT angiography (OCTA), and dense automatic real-time (ART) OCTA. New-onset cysts were considered IRF, whereas those cysts that were found to be persistent for at least 3 months were categorized as degenerative pseudocysts. Intraretinal cysts were automatically segmented to calculate cyst circularity. Peri-cyst space was quantitatively analyzed to assess the presence of perfusion signal and hyperreflective foci (HF).<br><br>MAIN OUTCOME MEASURES: Best-corrected visual acuity, cyst circularity, peri-cyst perfusion, peri-cyst HF, fibrosis, and outer retinal atrophy.<br><br>RESULTS: We analyzed 387 cysts collected from 35 eyes of 35 patients with neovascular AMD (14 men; mean age, 80 &#xb1; 5 years). We classified 302 IRF cysts and 85 degenerative pseudocysts. Intraretinal fluid cysts were characterized by significantly higher circularity (0.86; range, 0.81-0.91), perfusion signal in the peri-cyst space, and peri-cyst HF in 89% of cases (all P < 0.05). Degenerative pseudocysts showed significantly lower circularity (0.68; range, 0.64-0.76), no perfusion signal in the peri-cyst space, and peri-cyst HF in only 29% of cases (all P < 0.05). The adopted quantitative metrics significantly correlated with disease duration, number of injections, fibrosis, and outer retinal atrophy.<br><br>CONCLUSIONS: Intraretinal fluid cysts can be discriminated from degenerative pseudocysts using a quantitative multimodal imaging approach. These findings are clinically relevant and should be included in future training models for artificial intelligence algorithms to improve the diagnostic power and fluid monitoring in neovascular AMD.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid38848188,
year = {2024},
author = {Gibbons, LE and Mobley, T and Mayeda, ER and Lee, CS and Gatto, NM and LaCroix, AZ and McEvoy, LK and Crane, PK and Hayes-Larson, E},
title = {How Generalizable Are Findings from a Community-Based Prospective Cohort Study? Extending Estimates from the Adult Changes in Thought Study to Its Source Population.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {100},
number = {1},
pages = {163-174},
pmid = {38848188},
issn = {1875-8908},
support = {R01 AG060942/AG/NIA NIH HHS/United States ; R56 AG069126/AG/NIA NIH HHS/United States ; P50 AG005136/AG/NIA NIH HHS/United States ; K99 AG075317/AG/NIA NIH HHS/United States ; U01 AG006781/AG/NIA NIH HHS/United States ; U19 AG066567/AG/NIA NIH HHS/United States ; R13 AG030995/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Cohort Studies ; Prospective Studies ; *Alzheimer Disease/epidemiology ; Eye Diseases/epidemiology ; Washington/epidemiology ; Prevalence ; Proportional Hazards Models ; Behavioral Risk Factor Surveillance System ; Residence Characteristics ; },
abstract = {BACKGROUND: The Adult Changes in Thought (ACT) study is a cohort of Kaiser Permanente Washington members ages 65+ that began in 1994.<br><br>OBJECTIVE: We wanted to know how well ACT participants represented all older adults in the region, and how well ACT findings on eye disease and its relationship with Alzheimer's disease generalized to all older adults in the Seattle Metropolitan Region.<br><br>METHODS: We used participation weights derived from pooling ACT and Behavioral Risk Factor Surveillance System (BRFSS) data to estimate prevalences of common eye diseases and their associations with Alzheimer's disease incidence. Cox proportional hazards models accounted for age, education, smoking, sex, and APOE genotype. Confidence intervals for weighted analyses were bootstrapped to account for error in estimating the weights.<br><br>RESULTS: ACT participants were fairly similar to older adults in the region. The largest differences were more self-reported current cholesterol medication use in BRFSS and higher proportions with low education in ACT. Incorporating the weights had little impact on prevalence estimates for age-related macular degeneration or glaucoma. Weighted estimates were slightly higher for diabetic retinopathy (weighted 5.7% (95% Confidence Interval 4.3, 7.1); unweighted 4.1% (3.6, 4.6)) and cataract history (weighted 51.8% (49.6, 54.3); unweighted 48.6% (47.3, 49.9)). The weighted hazard ratio for recent diabetic retinopathy diagnosis and Alzheimer's disease was 1.84 (0.34, 4.29), versus 1.32 (0.87, 2.00) in unweighted ACT.<br><br>CONCLUSIONS: Most, but not all, associations were similar after participation weighting. Even in community-based cohorts, extending inferences to broader populations may benefit from evaluation with participation weights.},
}
@article {pmid38847896,
year = {2024},
author = {Agostini, H and Abreu, F and Baumal, CR and Chang, DS and G Csaky, K and Demetriades, AM and Kodjikian, L and Lim, JI and Margaron, P and Monés, JM and Peto, T and Ricci, F and Rüth, M and Singh, RP and Stoilov, I and Swaminathan, B and Willis, JR and Westenskow, PD},
title = {Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3437-3451},
pmid = {38847896},
issn = {1435-702X},
support = {Medical writing support//Roche/ ; },
mesh = {Humans ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Angiopoietin-2/antagonists &amp; inhibitors ; *Antibodies, Bispecific/administration &amp; dosage ; Diabetic Retinopathy/drug therapy/diagnosis ; Intravitreal Injections ; *Macular Edema/drug therapy/etiology/diagnosis ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Clinical Trials as Topic ; Drug Evaluation, Preclinical ; },
abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); however, vision gains and anatomical improvements are not sustained over longer periods of treatment, suggesting other relevant targets may be needed to optimize treatments. Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation. Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE/RHINE) and nAMD (TENAYA/LUCERNE). These trials evaluated faricimab against the anti-VEGFA/B and anti-placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1 year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE/RHINE and TENAYA/LUCERNE. In YOSEMITE/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0-12 weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE/RHINE and TENAYA/LUCERNE. These findings suggest that dual Ang-2/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy.},
}
@article {pmid38847895,
year = {2024},
author = {Stradiotto, E and Ottonelli, G and Romano, MR and La Spina, C},
title = {Comment on "Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration".},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3733-3734},
pmid = {38847895},
issn = {1435-702X},
}
@article {pmid38846070,
year = {2024},
author = {Nihei, A and Yamamoto, M and Hirayama, K and Kyo, A and Misawa, N and Kohno, T and Honda, S},
title = {The impact of removing the epiretinal membrane and inner limiting membrane for sustained subretinal fluid by macular neovascularization refractory to anti-VEGF therapy.},
journal = {American journal of ophthalmology case reports},
volume = {35},
number = {},
pages = {102078},
pmid = {38846070},
issn = {2451-9936},
abstract = {PURPOSE: Anti-vascular endothelial growth factor (VEGF) therapy is the most prevalent intervention for exudative lesions secondary to neovascular age-related macular degeneration (nAMD) and other macular neovascularization (MNV). However, in some cases refractory to the latest anti-VEGF agents is associated with epiretinal membrane (ERM) or vitreomacular traction. We applied a vitrectomy to remove those pathologies which may be effective for reducing the exudation.<br><br>OBSERVATIONS: In this case report, we present 2 cases with sustained subretinal fluid and macular neovascularization secondary to nAMD or dome-shaped macula that poorly responded to anti-VEGF therapy. In both cases, removing thin ERM or vitreomacular traction with an inner limiting membrane peeling promptly resolved the subretinal fluid and no recurrence was observed thereafter.<br><br>CONCLUSIONS AND IMPORTANCE: Vitrectomy could be an effective modality for anti-VEGF drug-resistant MNV cases with vitreomacular traction or ERM even in the anti-VEGF era.},
}
@article {pmid38845112,
year = {2024},
author = {Balaratnasingam, C and Curcio, CA},
title = {Biomarkers in age-related macular degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {4},
pages = {384-386},
doi = {10.1111/ceo.14404},
pmid = {38845112},
issn = {1442-9071},
mesh = {Humans ; *Biomarkers/blood ; *Macular Degeneration/diagnosis ; },
}
@article {pmid38844476,
year = {2024},
author = {Grunin, M and Triffon, D and Beykin, G and Rahmani, E and Schweiger, R and Tiosano, L and Khateb, S and Hagbi-Levi, S and Rinsky, B and Munitz, R and Winkler, TW and Heid, IM and Halperin, E and Carmi, S and Chowers, I},
title = {Genome wide association study and genomic risk prediction of age related macular degeneration in Israel.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13034},
pmid = {38844476},
issn = {2045-2322},
support = {R01 EY022310/EY/NEI NIH HHS/United States ; 3-17354//Ministry of Science, Technology and Space/ ; M2021006F//BrightFocus Foundation/ ; 3485/19//Israel Science Foundation/ ; },
mesh = {Humans ; *Macular Degeneration/genetics/epidemiology ; Israel/epidemiology ; *Genome-Wide Association Study ; Female ; Male ; *Genetic Predisposition to Disease ; Aged ; *Polymorphism, Single Nucleotide ; Risk Factors ; Middle Aged ; Case-Control Studies ; Aged, 80 and over ; Multifactorial Inheritance/genetics ; Jews/genetics ; Genotype ; },
abstract = {The risk of developing age-related macular degeneration (AMD) is influenced by genetic background. In 2016, the International AMD Genomics Consortium (IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score (PRS) from these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish (AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study (GWAS) for AMD in Israel, and to evaluate PRSs for AMD. Our discovery set recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary-statistics excluding our study and developed PRSs via clumping/thresholding or LDpred2. In our discovery set, 31/34 loci reported by IAMDGC were AMD-associated (P < 0.05). Of those, all effects were directionally consistent with IAMDGC and 11 loci had a P-value under Bonferroni-corrected threshold (0.05/34 = 0.0015). At a 5 × 10[-5] threshold, we discovered four suggestive associations in FAM189A1, IGDCC4, C7orf50, and CNTNAP4. Only the FAM189A1 variant was AMD-associated in the replication cohort after Bonferroni-correction. A prediction model including LDpred2-based PRS + covariates had an AUC of 0.82 (95% CI 0.79-0.85) and performed better than covariates-only model (P = 5.1 × 10[-9]). Therefore, previously reported AMD-associated loci were nominally associated with AMD in Israel. A PRS developed based on a large international study is predictive in Israeli populations.},
}
@article {pmid38844200,
year = {2024},
author = {Sacconi, R and Fazzari, G and Capuano, V and Menean, M and Beretta, F and El Matri, K and Bandello, F and Souied, E and Querques, G},
title = {Pachy-Reticular Pseudodrusen.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {11},
pages = {1066-1073},
doi = {10.1016/j.oret.2024.05.020},
pmid = {38844200},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Case-Control Studies ; *Choroid/blood supply/diagnostic imaging/pathology ; *Fluorescein Angiography/methods ; Follow-Up Studies ; *Fundus Oculi ; Multimodal Imaging ; *Retinal Drusen/diagnosis/etiology ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Visual Acuity ; },
abstract = {PURPOSE: To characterize the features of a peculiar association between reticular pseudodrusen (RPD) and pachychoroid (pachy-RPD) and to compare them with eyes affected by RPD and normal/leptochoroid.<br><br>DESIGN: Observational, retrospective, case-control study.<br><br>PARTICIPANTS: Among a cohort of patients with intermediate age-related macular degeneration (AMD), we selected eyes with RPD and pachychoroid (i.e., choroidal thickness of >50 &#x3bc;m). A control group of RPD eyes but without pachychoroid (i.e., a choroidal thickness of <250 &#x3bc;m) was included.<br><br>METHODS: Number and stages of RPD were evaluated in each ETDRS subfield. Furthermore, choroidal perfusion was investigated using the choroidal vascularity index (CVI), and choriocapillaris perfusion density (PD) on structural OCT and OCT angiography.<br><br>MAIN OUTCOME MEASURES: Description of the multimodal imaging features of pachy-RPD and differences with RPD associated with normal/leptochoroid.<br><br>RESULTS: Among 111 RPD eyes, 37 were included in the pachy-RPD group and 74 in the control group. Patients with pachy-RPD were significantly younger than patients with RPD and normal/leptochoroid (mean age, 75 &#xb1; 16 and 82 &#xb1; 7 years, respectively; P&#xa0;= 0.002). Total RPD number was comparable between the 2 groups (P&#xa0;= 0.220). However, pachy-RPD eyes showed a significantly higher number of stage 1 RPD in comparison to the controls (P < 0.001), and a lower number of stage 3 (P < 0.001) and stage 4 RPD (P&#xa0;=&#xa0;0.052). The CVI and choriocapillaris PD were greater in pachy-RPD than in the control group (P < 0.001 and P= 0.010, respectively).<br><br>CONCLUSIONS: Pachy-RPD are characterized by a different distribution of RPD stages (i.e., more early stages and fewer advanced stages) in comparison to RPD with normal/leptochoroid. Furthermore, pachy-RPD eyes showed greater perfusion indices of the choroid. These features suggest that the presence of pachychoroid could be a protective factor in the RPD evolution to the advanced AMD forms.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38843050,
year = {2024},
author = {Zhang, G and Qu, Y and Wu, Z and Liu, W and Luo, H and Chen, R and Jia, H and Sun, X},
title = {Association between low lung function and the increased risk of age-related macular degeneration: A population-based prospective cohort study.},
journal = {Journal of global health},
volume = {14},
number = {},
pages = {04102},
pmid = {38843050},
issn = {2047-2986},
mesh = {Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; *Macular Degeneration/epidemiology ; Aged ; Risk Factors ; United Kingdom/epidemiology ; Lung/physiopathology ; Respiratory Function Tests ; Incidence ; Adult ; Proportional Hazards Models ; },
abstract = {BACKGROUND: Low lung function is associated with an increased risk of age-related diseases. However, the relationship between age-related macular degeneration (AMD), the leading cause of blindness, and lung function remains unclear. We aimed to investigate whether low lung function increases the risk of AMD and the potential mechanisms behind this association.<br><br>METHODS: We conducted a prospective cohort analysis of 409&#x2009;230 UK Biobank participants with completed lung function after excluding individuals with AMD. We used Cox proportional hazards models to estimate the risk of AMD incidence and mediation models to explore potential mechanisms driven by inflammatory markers, erythrocyte-related measures, and metabolites.<br><br>RESULTS: Overall, 6477 AMD cases were diagnosed across an average of 12.4 years of follow-up. Participants with low lung function had an increased risk of developing AMD compared to those with high lung function (forced vital capacity: adjusted hazard ratio (aHR)&#x2009;=&#x2009;1.20 (95% confidence interval (CI)&#x2009;=&#x2009;1.07-1.34); forced expiratory volume in one second: aHR&#x2009;=&#x2009;1.32 (95% CI&#x2009;=&#x2009;1.18-1.47); peak expiratory flow: aHR&#x2009;=&#x2009;1.32 (95% CI&#x2009;=&#x2009;1.20-1.45)). Inflammatory markers and erythrocyte-related measures mediated this relationship, acting as a pathway through which low lung function influenced AMD. The interactions of body mass index (BMI), sex, and smoking were significant and the effect of lung function on AMD was higher in men, obese, and smoking populations.<br><br>CONCLUSIONS: The increased risk of AMD was associated with low lung function, with inflammatory and erythrocyte-related markers mediating this relationship. This suggests that improvements in lung function could reduce the risk of AMD, thereby promoting health and longevity.},
}
@article {pmid38842832,
year = {2024},
author = {Jeong, H and Shaia, JK and Markle, JC and Talcott, KE and Singh, RP},
title = {Melatonin and Risk of Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {142},
number = {7},
pages = {648-654},
pmid = {38842832},
issn = {2168-6173},
mesh = {Humans ; *Melatonin/therapeutic use/administration &amp; dosage ; Female ; Male ; Retrospective Studies ; Aged ; Middle Aged ; *Macular Degeneration/epidemiology ; Risk Factors ; Disease Progression ; Aged, 80 and over ; United States/epidemiology ; Incidence ; },
abstract = {IMPORTANCE: Melatonin has been shown to oppose several processes that are known to mediate age-related macular degeneration (AMD), but whether melatonin can confer benefits against AMD remains unclear.<br><br>OBJECTIVE: To examine the association between melatonin supplementation and the risk of the development or progression of AMD.<br><br>This retrospective cohort study accessed data from TriNetX, a national database of deidentified electronic medical records from both inpatient and outpatient health care organizations across the US, between December 4, 2023, and March 19, 2024. Patients aged 50 years or older, 60 years or older, and 70 years or older with no history of AMD (AMD-naive group) and with a history of nonexudative AMD (nonexudative AMD group) were queried for instances of melatonin medication codes between November 14, 2008, and November 14, 2023. Patients were then classified into either a melatonin group or a control group based on the presence of medication codes for melatonin. Propensity score matching (PSM) was performed to match the cohorts based on demographic variables, comorbidities, and nonmelatonin hypnotic medication use.<br><br>EXPOSURE: The presence of at least 4 instances of melatonin records that each occurred at least 3 months apart.<br><br>MAIN OUTCOMES AND MEASURES: After PSM, the melatonin and the control cohorts were compared to evaluate the risk ratios (RRs) and the 95% CIs of having an outcome. For the AMD-naive group, the outcome was defined as a new diagnosis of any AMD, whereas for the nonexudative AMD group, the outcome was progression to exudative AMD.<br><br>RESULTS: Among 121&#x202f;523 patients in the melatonin-naive group aged 50 years or older (4848 in the melatonin cohort [4580 after PSM; mean (SD) age, 68.24 (11.47) years; 2588 female (56.5%)] and 116&#x202f;675 in the control cohort [4580 after PSM; mean (SD) age, 68.17 (10.63) years; 2681 female (58.5%)]), melatonin use was associated with a reduced risk of developing AMD (RR, 0.42; 95% CI, 0.28-0.62). Among 66&#x202f;253 patients aged 50 years or older in the nonexudative AMD group (4350 in the melatonin cohort [4064 after PSM; mean (SD) age, 80.21 (8.78) years; 2482 female (61.1%)] and 61&#x202f;903 in the control cohort [4064 patients after PSM; mean (SD) age, 80.31 (8.03) years; 2531 female (62.3%)]), melatonin was associated with a reduced risk of AMD progression to exudative AMD (RR, 0.44; 95% CI, 0.34-0.56). The results were consistent among subsets of individuals aged 60 years or older (AMD-naive cohort: RR, 0.36 [95% CI, 0.25-0.54]; nonexudative AMD cohort: RR, 0.38 [95% CI, 0.30-0.49]) and 70 years or older (AMD-naive cohort: RR, 0.35 [95% CI, 0.23-0.53]; nonexudative AMD cohort: RR, 0.40 [95% CI, 0.31-0.51]).<br><br>CONCLUSIONS AND RELEVANCE: Melatonin use was associated with a decreased risk of development and progression of AMD. Although lifestyle factors may have influenced this association, these findings provide a rationale for further research on the efficacy of using melatonin as a preventive therapy against AMD.},
}
@article {pmid38842593,
year = {2024},
author = {Künzel, SE and Frentzel, DP and Flesch, LTM and Knecht, VA and Rübsam, A and Dreher, F and Schütte, M and Dubrac, A and Lange, B and Yaspo, ML and Lehrach, H and Joussen, AM and Zeitz, O},
title = {AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3567-3575},
pmid = {38842593},
issn = {1435-702X},
support = {unrestricted research grant//Novartis Pharma/ ; },
mesh = {Humans ; *Biomarkers/blood ; Cross-Sectional Studies ; Male ; Female ; *Wet Macular Degeneration/diagnosis/blood/drug therapy ; *Xenobiotics/blood ; Aged ; *Tandem Mass Spectrometry ; Intravitreal Injections ; Chromatography, Liquid ; Angiogenesis Inhibitors/therapeutic use/blood ; Vascular Endothelial Growth Factor A/blood ; Artificial Intelligence ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; Random Forest ; },
abstract = {PURPOSE: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies.<br><br>METHODS: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes.<br><br>RESULTS: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl &#x3b2;-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence.<br><br>CONCLUSIONS: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.},
}
@article {pmid38840251,
year = {2024},
author = {Ojaghi, H and Poorsheykhian, S and Najafi, A and Iranpour, S},
title = {The role of blood related inflammatory factors on age-related macular degeneration (AMD).},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {21},
number = {1},
pages = {35},
pmid = {38840251},
issn = {1742-4933},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a significant retinal disease that leads to irreversible low vision, particularly in developing countries. The variation in AMD prevalence among different racial groups and highlighted role of inflammation on disease pathology from previous studies which yielded in inconsistent findings, It seems to be of great importance to do more investigation in this field.<br><br>METHODS: This case control study involved 204 participants, divided into four groups of equal size (51 individuals per group). Three groups represented AMD cases of varying severity according to Beckman classification (3 groups) and one healthy control group. Sampling was conducted exhaustively until the desired sample size was reached. The control group comprised healthy individuals without any infectious or inflammatory systemic, ophthalmic disease. Blood samples were collected to measure inflammatory factors, including lymphocytes, monocytes, neutrophils, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). Collected data were analyzed by statistical methods in SPSS version 21.<br><br>RESULTS: Of the participants, 51% were women, and their ages ranged from 47 to 89 years (62.2&#x2009;&#xb1;&#x2009;8). According to multiple logistic regression analysis, age exhibited a statistically significant positive association with AMD severity (P&#x2009;=&#x2009;0.038, odds ratio [OR]&#x2009;=&#x2009;1.034). ANOVA results indicated a significant association between neutrophil count and AMD severity (P&#x2009;<&#x2009;0.001). As the disease severity increased, the number of neutrophils decreased. The mean&#x2009;&#xb1;&#x2009;SD neutrophil counts for early, intermediate and advanced AMD were 3849&#x2009;&#xb1;&#x2009;800, 3702&#x2009;&#xb1;&#x2009;734, and 3342&#x2009;&#xb1;&#x2009;823, respectively. No statistically significant associations were found between lymphocyte count, monocyte count, neutrophil-to-lymphocyte ratio, CRP, and AMD.<br><br>CONCLUSION: There was a significant relationship between the number of neutrophils in peripheral blood and the severity of AMD in study participants which needs more evaluation for the potential utility of this factor in the prognosis of AMD. There was not any significant relationship among the other factors and AMD.},
}
@article {pmid38839719,
year = {2024},
author = {Giannos, SA and Kraft, ER and Luisi, JD and Schmitz-Brown, ME and Reffatto, V and Merkley, KH and Gupta, PK},
title = {Topical Solution for Retinal Delivery: Bevacizumab and Ranibizumab Eye Drops in Anti-Aggregation Formula (AAF) in Rabbits.},
journal = {Pharmaceutical research},
volume = {41},
number = {6},
pages = {1247-1256},
pmid = {38839719},
issn = {1573-904X},
mesh = {Animals ; *Ranibizumab/administration &amp; dosage/pharmacokinetics ; Rabbits ; *Bevacizumab/administration &amp; dosage/pharmacokinetics ; *Ophthalmic Solutions/administration &amp; dosage ; *Retina/metabolism/drug effects ; Angiogenesis Inhibitors/administration &amp; dosage/pharmacokinetics ; Vitreous Body/metabolism ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Biosimilar Pharmaceuticals/administration &amp; dosage/pharmacokinetics ; Wet Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: Wet age-related macular degeneration (AMD) is a blinding retinal disease. Monthly intravitreal anti-VEGF antibody injections of bevacizumab (off-label) and ranibizumab (FDA approved) are the standard of care. Antibody aggregation may interfere with ocular absorption/distribution. This study assessed topical delivery of dilute antibodies to the posterior segment of rabbit eyes using a novel anti-aggregation formula (AAF).<br><br>METHODS: Bevacizumab, or biosimilar ranibizumab was diluted to 5&#xa0;mg/ml in AAF. All rabbits were dosed twice daily. Substudy 1 rabbits (bevacizumab, 100&#xa0;&#xb5;l eye drops): Group 1 (bevacizumab/AAF, n&#x2009;=&#x2009;6); Group 2 (bevacizumab/PBS, n&#x2009;=&#x2009;7) and Vehicle control (AAF, n&#x2009;=&#x2009;1). Substudy 2 rabbits (ranibizumab biosimilar/AAF, 50&#xa0;&#xb5;l eye drops): (ranibizumab biosimilar/AAF, n&#x2009;=&#x2009;8). At 14.5&#xa0;days, serum was drawn from rabbits. Aqueous, vitreous and retina samples were recovered from eyes and placed into AAF aliquots. Tissue analyzed using AAF as diluent.<br><br>RESULTS: Bevacizumab in AAF permeated/accumulated in rabbit aqueous, vitreous and retina 10 times more, than when diluted in PBS. AAF/0.1% hyaluronic acid eye drops, dosed twice daily, provided mean tissue concentrations (ng/g) in retina (29.50), aqueous (12.34), vitreous (3.46), and serum (0.28&#xa0;ng/ml). Additionally, the highest concentration (ng/g) of ranibizumab biosimilar was present in the retina (18.0), followed by aqueous (7.82) and vitreous (1.47). Serum concentration was negligible (<&#x2009;0.04&#xa0;ng/ml). No irritation was observed throughout the studies.<br><br>CONCLUSIONS: Bevacizumab and ranibizumab, in an AAF diluent eye drop, can be delivered to the retina, by the twice daily dosing of a low concentration mAb formulation. This may prove to be an adjunct to intravitreal injections.},
}
@article {pmid38838135,
year = {2024},
author = {Liu, J and Copland, DA and Clare, AJ and Gorski, M and Richards, BT and Scott, L and Theodoropoulou, S and Greferath, U and Cox, K and Shi, G and Bell, OH and Ou, K and Powell, JLB and Wu, J and Robles, LM and Li, Y and Nicholson, LB and Coffey, PJ and Fletcher, EL and Guymer, R and Radeke, MJ and Heid, IM and Hageman, GS and Chan, YK and Dick, AD},
title = {Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration.},
journal = {Science translational medicine},
volume = {16},
number = {750},
pages = {eadi4125},
doi = {10.1126/scitranslmed.adi4125},
pmid = {38838135},
issn = {1946-6242},
mesh = {Animals ; Humans ; Male ; Mice ; Cellular Senescence ; *Interleukin-1 Receptor-Associated Kinases/metabolism/genetics ; Macular Degeneration/metabolism/pathology/genetics ; Mice, Inbred C57BL ; *Mice, Knockout ; Mitochondria/metabolism ; *Oxidative Stress ; *Retinal Degeneration/metabolism/pathology/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; },
abstract = {Chronic inflammation is a constitutive component of many age-related diseases, including age-related macular degeneration (AMD). Here, we identified interleukin-1 receptor-associated kinase M (IRAK-M) as a key immunoregulator in retinal pigment epithelium (RPE) that declines during the aging process. Rare genetic variants of IRAK3, which encodes IRAK-M, were associated with an increased likelihood of developing AMD. In human samples and mouse models, IRAK-M abundance in the RPE declined with advancing age or exposure to oxidative stress and was further reduced in AMD. Irak3-knockout mice exhibited an increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M led to a disruption in RPE cell homeostasis, characterized by compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of adeno-associated virus (AAV)-expressing human IRAK3 rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in Irak3-knockout mice. Our data show that replenishment of IRAK-M in the RPE may redress dysregulated pro-inflammatory processes in AMD, suggesting a potential treatment for retinal degeneration.},
}
@article {pmid38837967,
year = {2024},
author = {Azizi, MM and Abhari, S and Sajedi, H},
title = {Stitched vision transformer for age-related macular degeneration detection using retinal optical coherence tomography images.},
journal = {PloS one},
volume = {19},
number = {6},
pages = {e0304943},
pmid = {38837967},
issn = {1932-6203},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/diagnostic imaging ; *Retina/diagnostic imaging/pathology ; *Neural Networks, Computer ; Aged ; Algorithms ; },
abstract = {Age-related macular degeneration (AMD) is an eye disease that leads to the deterioration of the central vision area of the eye and can gradually result in vision loss in elderly individuals. Early identification of this disease can significantly impact patient treatment outcomes. Furthermore, given the increasing elderly population globally, the importance of automated methods for rapidly monitoring at-risk individuals and accurately diagnosing AMD is growing daily. One standard method for diagnosing AMD is using optical coherence tomography (OCT) images as a non-invasive imaging technology. In recent years, numerous deep neural networks have been proposed for the classification of OCT images. Utilizing pre-trained neural networks can speed up model deployment in related tasks without compromising accuracy. However, most previous methods overlook the feasibility of leveraging pre-existing trained networks to search for an optimal architecture for AMD staging on a new target dataset. In this study, our objective was to achieve an optimal architecture in the efficiency-accuracy trade-off for classifying retinal OCT images. To this end, we employed pre-trained medical vision transformer (MedViT) models. MedViT combines convolutional and transformer neural networks, explicitly designed for medical image classification. Our approach involved pre-training two distinct MedViT models on a source dataset with labels identical to those in the target dataset. This pre-training was conducted in a supervised manner. Subsequently, we evaluated the performance of the pre-trained MedViT models for classifying retinal OCT images from the target Noor Eye Hospital (NEH) dataset into the normal, drusen, and choroidal neovascularization (CNV) classes in zero-shot settings and through five-fold cross-validation. Then, we proposed a stitching approach to search for an optimal model from two MedViT family models. The proposed stitching method is an efficient architecture search algorithm known as stitchable neural networks. Stitchable neural networks create a candidate model in search space for each pair of stitchable layers by inserting a linear layer between them. A pair of stitchable layers consists of layers, each selected from one input model. While stitchable neural networks had previously been tested on more extensive and general datasets, this study demonstrated that stitching networks could also be helpful in smaller medical datasets. The results of this approach indicate that when pre-trained models were available for OCT images from another dataset, it was possible to achieve a model in 100 epochs with an accuracy of over 94.9% in classifying images from the NEH dataset. The results of this study demonstrate the efficacy of stitchable neural networks as a fine-tuning method for OCT image classification. This approach not only leads to higher accuracy but also considers architecture optimization at a reasonable computational cost.},
}
@article {pmid38835885,
year = {2024},
author = {Kohnen, T and Hammond, BR},
title = {Blue Light Filtration in Intraocular Lenses: Effects on Visual Function and Systemic Health.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {1575-1586},
pmid = {38835885},
issn = {1177-5467},
abstract = {Blue light-filtering (BLF) intraocular lenses (IOLs) are designed to mimic the healthy natural adult crystalline lens. Studies that evaluated the relative merit of ultraviolet-only IOL design (ie, blocking wavelengths <400 nm) versus BLF IOL design (ie, filtering wavelengths ~400-475 nm in addition to blocking wavelengths <400 nm) on protection and function of the visual system suggest that neither design had a deleterious impact on visual acuity or contrast sensitivity. A BLF design may reduce some aspects of glare, such as veiling and photostress. BLF has been shown in many contexts to improve visual performance under conditions that are stressed by blue light, such as distance vision impaired by short-wave dominant haze. Furthermore, some data (mostly inferential) support the notion that BLF IOLs reduce actinic stress. Biomimetic BLF IOLs represent a conservative approach to IOL design that provides no harm for visual acuity, contrast sensitivity, or color vision while improving vision under certain circumstances (eg, glare).},
}
@article {pmid38835666,
year = {2024},
author = {Shen, X and Kong, F and Wen, J and Wang, X and Huang, C},
title = {The role of inflammation in central serous chorioretinopathy: From mechanisms to therapeutic prospects.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1200492},
pmid = {38835666},
issn = {1663-9812},
abstract = {Central serous chorioretinopathy (CSC) is a leading cause of permanent vision loss, ranking fourth among macular diseases, trailing only age-related macular degeneration, diabetic retinopathy, and retinal vein obstruction. While mounting evidence implicates inflammation as a pivotal factor in the onset and advancement of CSC, the specific pathophysiological process and molecular mechanisms underlying inflammation remain incompletely understood. A complex network of cytokines, chemokines, and adhesion molecules interplay to trigger inflammatory and pathological cascades, highlighting the need for a comprehensive comprehension of the inflammation-related mechanisms behind CSC progression. In this piece, we examine the existing comprehension of CSC's pathology and pathogenesis. Additionally, we present an overview of the mechanisms underlying the onset and progression of CSC inflammation, followed by a thorough analysis and discussion of the potential of targeted inflammatory intervention for both preventing and treating CSC.},
}
@article {pmid38835123,
year = {2024},
author = {Hu, X and Liu, F and Yang, H and Qi, M and Ren, Y and Zhu, W and Dai, C},
title = {Protective Effect and Related Mechanism of Modified Danggui Buxue Decoction on Retinal Oxidative Damage in Mice based on Network Pharmacology.},
journal = {Current pharmaceutical design},
volume = {30},
number = {24},
pages = {1912-1926},
pmid = {38835123},
issn = {1873-4286},
mesh = {Animals ; *Drugs, Chinese Herbal/pharmacology ; Mice ; *Oxidative Stress/drug effects ; *Network Pharmacology ; Male ; Retina/drug effects/metabolism ; Protective Agents/pharmacology ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is one of the common diseases that cause vision loss in the elderly, and oxidative stress has been considered a major pathogenic factor for AMD. Modified Danggui Buxue Decoction (RRP) has a good therapeutic effect on non-proliferatic diabetic retinopathy and can improve the clinical symptoms of patients.<br><br>METHODS: The key ingredients and core targets of RRP protecting retinal oxidative damage were obtained by Network pharmacology analysis. A mouse retinal oxidative damage model induced by tail vein injection of 1% NaIO3 solution (25 mg/kg) was treated with RRP for 4 weeks and used to verify the pharmacodynamics and related mechanism.<br><br>AIM: This study aimed to predict and verify the protective effect and mechanism of RRP on retinal oxidative damage in mice based on network pharmacology and animal experiments.<br><br>RESULTS: A total of 15 key active components included in RRP interacted with 57 core targets related to retinal oxidative damage (such as AKT1, NFE2L2, HMOX1), mainly involved in the AGE-RAGE signaling pathway in diabetic complications, PI3K-AKT signaling pathway and so on. Further studies in vivo found that RRP improved the retinal oxidative damage, increased the content of SOD and GSH, decreased the content of MDA in mouse serum, promoted the expression of p-PI3K, p-AKT, Nrf2, HO-1 and NQO1 proteins in the mouse retina, and inhibited the expression of Nrf2 in the cytoplasm.<br><br>CONCLUSION: This study revealed that RRP had a protective effect on oxidative damage of the retina in mice, and might exert anti-oxidative effect by activating the PI3K/Akt/Nrf2 signal pathway. This study provided scientific data for the further development of hospital preparations of RRP, and a good theoretical basis for the clinical application of RRP.},
}
@article {pmid38835087,
year = {2024},
author = {Myers, V and Luxenburg, O and Wilf-Miron, R and Verbin, HL},
title = {Timely care for age-related macular degeneration: a qualitative study among retina specialists in Israel.},
journal = {Israel journal of health policy research},
volume = {13},
number = {1},
pages = {28},
pmid = {38835087},
issn = {2045-4015},
support = {9.19 2019/4//Israel National Institute for Health Policy Research/ ; },
mesh = {Humans ; Israel/epidemiology ; *Qualitative Research ; *Macular Degeneration/therapy ; Male ; Female ; Interviews as Topic ; Middle Aged ; Ophthalmologists/statistics &amp; numerical data ; Referral and Consultation/statistics &amp; numerical data ; Quality of Life/psychology ; Health Services Accessibility ; Adult ; Aged ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) affects quality of life and independence, and its incidence and prevalence are increasing due to ageing of the population. Access to effective timely treatment can improve vision and reduce incidence of blindness. This study aimed to explore the perspectives of ophthalmologists in the Israeli public healthcare system regarding timely treatment of AMD patients.<br><br>METHODS: Qualitative semi-structured interviews were conducted in 2020-2021 with 22 senior ophthalmologists, from 10 general hospitals and from two HMOs, representing different geographic regions. All interviewees specialize in retinal diseases and work with AMD patients. Interviews discussed patient pathways involved in the diagnosis and treatment of AMD, access to care, and obstacles to timely care. Thematic analysis was conducted.<br><br>RESULTS: Based on the interviews, we describe the usual referral and treatment pathways. Themes included regional disparities, long wait times in some areas, a lack of retina specialists, differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second-line treatment not fully covered by insurance, most affecting the weakest segments of the population.<br><br>CONCLUSIONS: Loss of vision incurs high health and societal costs. In the context of insufficient medical manpower in Israel, the healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population. Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. Awareness of AMD symptoms and the importance of early intervention could be highlighted by campaigns, particularly among high-risk groups.<br><br>HIGHLIGHTS: &#x2022; Interviews with hospital-based and community ophthalmologists showed regional disparities in AMD treatment, with long wait times and a lack of retina specialists in some areas. &#x2022; Differences in referral pathways, inappropriate use of emergency department to obtain timely treatment, and second line treatment not fully covered by insurance were highlighted. &#x2022; The healthcare system will need to assess future resources to cope with accumulating burden of AMD cases over time in an ageing population &#x2022; Precise referral information, and simultaneous referral to imaging and retinal clinics, may minimize delays in treatment. &#x2022; Awareness of AMD symptoms and the importance of early intervention should be emphasized in high-risk groups.},
}
@article {pmid38834171,
year = {2025},
author = {Chong, DD and Maatouk, CM and Markle, J and Shaia, JK and Singh, RP and Talcott, KE},
title = {Cardiovascular risk in anti-VEGF treatment of neovascular age-related macular degeneration.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {1},
pages = {35-41},
doi = {10.1016/j.jcjo.2024.05.013},
pmid = {38834171},
issn = {1715-3360},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Bevacizumab/administration &amp; dosage ; *Cardiovascular Diseases/epidemiology/etiology/mortality ; Follow-Up Studies ; Incidence ; Intravitreal Injections ; *Ranibizumab/administration &amp; dosage ; Retrospective Studies ; Risk Assessment/methods ; Risk Factors ; United States/epidemiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {OBJECTIVE: Assess 5-year all-cause mortality (ACM), hemorrhagic stroke, ischemic stroke, and myocardial infarction (MI) risks in nAMD patients receiving anti-VEGF injections compared with controls.<br><br>DESIGN: Population-based retrospective cohort study using a U.S. federated health research network, containing de-identified data of 96 million patients from 1/1/2003 to 3/6/2023.<br><br>PARTICIPANTS: nAMD Patients with anti-VEGF injections. Controls included nAMD patients without anti-VEGF injections, non-exudative AMD patients, and patients without AMD.<br><br>METHODS: Patients were identified using nAMD ICD-10 and anti-VEGF CPT codes and matched for age, sex, and comorbidities. Five-year relative risk of ACM (RR1), hemorrhagic stroke (RR2), ischemic stroke (RR3), and MI (RR4) in nAMD patients receiving anti-VEGF injections were calculated.<br><br>RESULTS: A total of 27,609 nAMD patients (mean diagnosis age [SD], [78.2 (10.3)]) received anti-VEGF injections; 769 nAMD patients without injections (75.8 [12.2]), 27,599 non-exudative AMD patients (78.2 [10.3]), and 21,902 no-AMD patients (76.1 [10.5]) were identified. After matching, nAMD patients receiving injections did not show increased risk versus nAMD patients without injections (RR1, 0.66; 95% CI [0.53, 0.82]), (RR2, 1.00 [0.42, 2.38]), (RR3, 1.70 [0.92,3.13]), (RR4, 0.63 [0.33, 1.18]). No increased risk was found compared to non-exudative AMD patients (RR1, 0.99 [0.95, 1.03]), (RR2, 0.94 [0.83,1.07]), (RR3, 1.04 [0.96, 1.12]), (RR4, 0.99 [0.91, 1.08]). Increased risk for ACM was observed versus no-AMD patients (RR1, 1.21 [1.15, 1.27]), but no other differences were found (RR2, 0.81 [0.70, 0.93]), (RR3, 1.00 [0.92, 1.09]), (RR4, 0.986 [0.90, 1.09]).<br><br>CONCLUSION: Anti-VEGF injections were not associated with major cardiovascular events in nAMD patients over 5 years.},
}
@article {pmid38833447,
year = {2024},
author = {Bakri, SJ and Lynch, J and Howard-Sparks, M and Saint-Juste, S and Saim, S},
title = {Vorolanib, sunitinib, and axitinib: A comparative study of vascular endothelial growth factor receptor inhibitors and their anti-angiogenic effects.},
journal = {PloS one},
volume = {19},
number = {6},
pages = {e0304782},
pmid = {38833447},
issn = {1932-6203},
mesh = {*Axitinib/pharmacology ; Humans ; *Sunitinib/pharmacology ; *Angiogenesis Inhibitors/pharmacology ; *Imidazoles/pharmacology ; *Pyrroles/pharmacology ; *Indoles/pharmacology ; *Human Umbilical Vein Endothelial Cells ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors/metabolism ; *Indazoles/pharmacology ; Animals ; *Protein Kinase Inhibitors/pharmacology ; Receptor, TIE-2/metabolism/antagonists &amp; inhibitors ; Neovascularization, Pathologic/drug therapy/metabolism ; },
abstract = {PURPOSE: Pathological angiogenesis and vascular instability are observed in diabetic retinopathy (DR), diabetic macular edema (DME), and wet age-related macular degeneration (wAMD). Many receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptors (VEGFRs) contribute to angiogenesis, whereas the RTK TIE2 is important for vascular stability. Pan-VEGFR tyrosine kinase inhibitors (TKIs) such as vorolanib, sunitinib, and axitinib are of therapeutic interest over current antibody treatments that target only one or two ligands. This study compared the anti-angiogenic potential of these TKIs.<br><br>METHODS: A kinase HotSpot&#x2122; assay was conducted to identify TKIs inhibiting RTKs associated with angiogenesis and vascular stability. Half-maximal inhibitory concentration (IC50) for VEGFRs and TIE2 was determined for each TKI. In vitro angiogenesis inhibition was investigated using a human umbilical vein endothelial cell sprouting assay, and in vivo angiogenesis was studied using the chorioallantoic membrane assay. Melanin binding was assessed using a melanin-binding assay. Computer modeling was conducted to understand the TIE2-axitinib complex as well as interactions between vorolanib and VEGFRs.<br><br>RESULTS: Vorolanib, sunitinib, and axitinib inhibited RTKs of interest in angiogenesis and exhibited pan-VEGFR inhibition. HotSpot&#x2122; assay and TIE2 IC50 values showed that only axitinib potently inhibited TIE2 (up to 89%). All three TKIs effectively inhibited angiogenesis in vitro. In vivo, TKIs were more effective at inhibiting VEGF-induced angiogenesis than the anti-VEGF antibody bevacizumab. Of the three TKIs, only sunitinib bound melanin. TKIs differ in their classification and binding to VEGFRs, which is important because type II inhibitors have greater selectivity than type I TKIs.<br><br>CONCLUSIONS: Vorolanib, sunitinib, and axitinib exhibited pan-VEGFR inhibition and inhibited RTKs associated with pathological angiogenesis. Of the three TKIs, only axitinib potently inhibited TIE2 which is an undesired trait as TIE2 is essential for vascular stability. The findings support the use of vorolanib for therapeutic inhibition of angiogenesis observed in DR, DME, and wAMD.},
}
@article {pmid38833127,
year = {2024},
author = {Servillo, A and Sacconi, R and Oldoni, G and Barlocci, E and Tombolini, B and Battista, M and Fantaguzzi, F and Rissotto, F and Mularoni, C and Parravano, M and Zucchiatti, I and Querques, L and Bandello, F and Querques, G},
title = {Advancements in Imaging and Therapeutic Options for Dry Age-Related Macular Degeneration and Geographic Atrophy.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {8},
pages = {2067-2082},
pmid = {38833127},
issn = {2193-8245},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with dry AMD (d-AMD) leading to geographic atrophy (GA) and significant visual impairment. Multimodal imaging plays a crucial role in d-AMD diagnosis and management, allowing for detailed classification of patient phenotypes and aiding in treatment planning and prognosis determination. Treatment approaches for d-AMD have recently witnessed profound change with the development of specific drugs targeting the complement cascade, with the first anticomplement agents recently approved for GA treatment. Additionally, emerging strategies such as gene therapy and laser treatments may offer potential benefits, though further research is needed to fully establish their efficacy. However, the lack of effective therapies capable of restoring damaged retinal cells remains a major challenge. In the future, genetic treatments aimed at preventing the progression of d-AMD may emerge as a powerful approach. Currently, however, their development is still in the early stages.},
}
@article {pmid38832144,
year = {2024},
author = {Yoshikawa, Y and Sakaki, Y and Shinoda, K and Kataoka, K},
title = {Safety and Effectiveness of Intravitreal Brolucizumab Injection in Combination With Sub-Tenon's Capsule Triamcinolone Acetonide Injection for Polypoidal Choroidal Vasculopathy During the Loading Phase.},
journal = {Cureus},
volume = {16},
number = {5},
pages = {e59481},
pmid = {38832144},
issn = {2168-8184},
abstract = {BACKGROUND: This study evaluated the safety and effectiveness of combining intravitreal brolucizumab injection with sub-tenon's capsule triamcinolone acetonide injection (STTA) during the loading phase for polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: In this retrospective observational study, untreated patients with PCV receiving intravitreal brolucizumab injections with STTA during loading at Saitama Medical University Hospital's Eye Center from May 2021 to June 2022 were analyzed. Complete regression rates of polypoidal lesions were assessed using indocyanine green angiography 12 weeks post-treatment initiation.<br><br>RESULTS: Nineteen patients (19 eyes) participated. Best-corrected visual acuity significantly improved at eight weeks compared to baseline. No significant intraocular pressure increases occurred throughout the loading phase, while central foveal and choroidal thickness significantly reduced at 4, 8, and 12 weeks. Subretinal fluid was present in all patients before treatment, rapidly resolving post-intravitreal brolucizumab injections and STTA, with residual rates of 36.8% (seven eyes) and 5.3% (one eye) at four and 12 weeks, respectively. Intraocular inflammation did not occur during the loading phase, and the complete regression rate of polypoidal lesions was 89.5% (17 eyes).<br><br>CONCLUSIONS: Combining intravitreal brolucizumab injection with STTA during the loading phase may be one treatment option for PCV management.},
}
@article {pmid38831806,
year = {2024},
author = {Xiong, M and Yu, C and Ren, B and Zhong, M and Lu, J and Yuan, C and Sun, Q and Peng, Q and Zeng, M and Song, H},
title = {Global trends in oxidative stress in the Retina: A bibliometric analysis of 2013-2023.},
journal = {Heliyon},
volume = {10},
number = {10},
pages = {e31620},
pmid = {38831806},
issn = {2405-8440},
abstract = {BACKGROUND: Oxidative stress plays a significant role in the pathogenesis of many retinal diseases. However, only a few systematic bibliometric studies have been conducted. This study aims to visualize research hotspots and developmental trends in oxidative stress in the retina from 2013 to 2023 by analyzing bibliometric data.<br><br>METHODS: We retrieved papers on oxidative stress in the retina published between 2013 and 2023 from the Web of Science Core Collection. The data were visually analyzed using CiteSpace and VOSviewer software.<br><br>RESULTS: The total number of 2100 publications were included in the analysis. An overall increasing trend in the number of publications is observed between 2013 and 2023. Chinese publications were the most contributive, but United States publications were the most influential. Shanghai Jiao Tong University was the most active and prolific institution. Antioxidants was the most productive journal, while Oxidative Medicine and Cellular Longevity were the journals with the most-cited articles. Kaarniranta K, from Finland, was the most productive and influential author. Examination of co-cited references revealed that researchers in the field are primarily focused on investigating the molecular mechanisms, preventive strategies, and utilization of antioxidants to address retinal oxidative damage. Diabetic retinopathy, endothelial growth factor, retinitis pigmentosa, retinal degeneration, antioxidant response, retinal ganglion cells, and genes are the research hotspots in this field. Metabolism, sodium iodate, and system are at the forefront of research in this field.<br><br>CONCLUSION: Attention toward retinal oxidative stress has increased over the past decade. Current research focuses on the mechanisms of retinal diseases related to oxidative stress and the experimental study of antioxidants in retinal diseases, which may continue to be a trend in the future.},
}
@article {pmid38831127,
year = {2024},
author = {Giancipoli, E and Guglielmi, A and Bux, AV and Clima, GME and Pignatelli, F and Boscia, F and Viggiano, P and Boscia, G and Fortunato, F and Besozzi, G and Niro, A and Dore, S and Iaculli, C},
title = {Real-World Outcomes of a Loading Phase with Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration (n-AMD) and Diabetic Macular Edema (DME).},
journal = {Ophthalmology and therapy},
volume = {13},
number = {8},
pages = {2163-2184},
pmid = {38831127},
issn = {2193-8245},
abstract = {INTRODUCTION: The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration (n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers.<br><br>METHODS: Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit.<br><br>RESULTS: Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (&#xb1;&#x2009;standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (&#xb1;&#x2009;0.43) to 0.53 (&#xb1;&#x2009;0.36; P&#x2009;=&#x2009;0.13) and from 0.51 (&#xb1;&#x2009;0.34) to 0.32 (&#xb1;&#x2009;0.24; P: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: - 166.5&#xa0;&#x3bc;m; P&#x2009;=&#x2009;0.0009/DME: - 110.8&#xa0;&#x3bc;m; P&#x2009;=&#x2009;0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (>&#x2009;100&#xa0;&#x3bc;m) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME.<br><br>CONCLUSIONS: Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME.},
}
@article {pmid38830546,
year = {2024},
author = {Kaufmann, M and Han, Z},
title = {RPE melanin and its influence on the progression of AMD.},
journal = {Ageing research reviews},
volume = {99},
number = {},
pages = {102358},
pmid = {38830546},
issn = {1872-9649},
support = {T35 AG038047/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Melanins/metabolism ; *Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/metabolism ; *Oxidative Stress/physiology ; Disease Progression ; Animals ; },
abstract = {OBJECTIVE: The aim of this review article is to summarize the latest findings and current understanding of the origin of melanin in the retinal pigment epithelium (RPE), its function within the RPE, its role in the pathogenesis of age-related macular degeneration (AMD), its effect on retinal development, and its potential therapeutic benefit in the treatment of AMD.<br><br>METHODS: A comprehensive search of peer-reviewed journals was conducted using various combinations of key terms such as "melanin," "retinal pigment epithelium" or "RPE," "age-related macular degeneration" or AMD," "lipofuscin," "oxidative stress," and "albinism." Databases searched include PubMed, Scopus, Science Direct, and Google Scholar. 147 papers published between the years of 1957 and 2023 were considered with an emphasis on recent findings.<br><br>SUMMARY OF FINDINGS: AMD is thought to result from chronic oxidative stress within the RPE that results in cellular dysfunction, metabolic dysregulation, inflammation, and lipofuscin accumulation. Melanin functions as a photoscreener, free radical scavenger, and metal cation binding reservoir within the RPE. RPE melanin does not regenerate, and it undergoes degradation over time in response to chronic light exposure and oxidative stress. RPE melanin is important for retinal development and RPE function, and in the aging eye, melanin loss is associated with increased lipid peroxidation, inflammation, and the accumulation of toxic oxidized cellular products. Therefore, melanin-based treatments may serve to preserve RPE and retinal function in AMD.<br><br>CONCLUSIONS: The pathogenesis of AMD is not fully understood, but RPE dysfunction and melanin loss in response to chronic oxidative stress and inflammation are thought to be primary drivers of the disease. Due to melanin's antioxidative effects, melanin-based nanotechnology represents a promising avenue for the treatment of AMD.},
}
@article {pmid38829176,
year = {2024},
author = {Sunaga, T and Maeda, M and Saulle, R and Ng, SM and Sato, MT and Hasegawa, T and Mason, AN and Noma, H and Ota, E},
title = {Anti-vascular endothelial growth factor biosimilars for neovascular age-related macular degeneration.},
journal = {The Cochrane database of systematic reviews},
volume = {6},
number = {6},
pages = {CD015804},
pmid = {38829176},
issn = {1469-493X},
mesh = {Aged ; Humans ; *Angiogenesis Inhibitors/therapeutic use/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Aptamers, Nucleotide/therapeutic use ; *Bevacizumab/therapeutic use ; Bias ; *Biosimilar Pharmaceuticals/therapeutic use ; Choroidal Neovascularization/drug therapy ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Randomized Controlled Trials as Topic ; *Ranibizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/drug effects ; Middle Aged ; Male ; Female ; },
abstract = {RATIONALE: Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss and disability worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is an effective treatment option that helps to prevent vision loss or to improve visual acuity in people with neovascular AMD, treatment imposes a significant financial burden on patients and healthcare systems. A biosimilar is a biological product that has been developed to be nearly identical to a previously approved biological product. The use of biosimilars may help reduce costs and so may increase patient access to effective biologic medicines with similar levels of safety to the drugs on which they are based.<br><br>OBJECTIVES: To assess the benefits and harms of anti-VEGF biosimilar agents compared with their corresponding anti-VEGF agents (i.e. the reference products) that have obtained regulatory approval for intravitreal injections in people with neovascular AMD.<br><br>SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries together with reference checking and contact with study authors to identify studies that are included in the review. The latest search date was 2 June 2023.<br><br>ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) that compared approved anti-VEGF biosimilars with their reference products for treating the eyes of adult participants (&#x2265; 50 years) who had an active primary or recurrent choroidal neovascularization lesion secondary to neovascular AMD.<br><br>OUTCOMES: Our outcomes were: best-corrected visual acuity (BCVA), central subfield thickness (CST), vision-related quality of life, serious ocular and non-ocular adverse events (AE), treatment-emergent adverse events (TEAEs), anti-drug antibodies (ADAs), and serum concentrations of biosimilars and reference drugs.<br><br>RISK OF BIAS: We assessed the risk of bias (RoB) for seven outcomes reported in a summary of findings table by using the Cochrane RoB 2 tool.<br><br>SYNTHESIS METHODS: We synthesized results for each outcome using meta-analysis, where possible, by calculating risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for dichotomous outcomes and continuous outcomes, respectively. Where this was not possible due to the nature of the data, we summarized the results narratively. We used GRADE to assess the certainty of evidence for prespecified outcomes.<br><br>INCLUDED STUDIES: We included nine parallel-group multi-center RCTs that enrolled a total of 3814 participants (3814 participating eyes), with sample sizes that ranged from 160 to 705 participants per study. The mean age of the participants in these studies ranged from 67 to 76 years, and the proportion of women ranged from 26.5% to 58.7%. Ranibizumab (Lucentis) was the reference product in seven studies, and aflibercept (Eyelea) was the reference product in two others. All the included studies had been supported by industry. The follow-up periods ranged from 12 to 52 weeks (median 48 weeks). Five studies (56%) were conducted in multi-country settings across Europe, North America and Asia, two studies in India, and one each in Japan and the Republic of Korea. We judged all the included studies to have met high methodological standards.<br><br>SYNTHESIS OF RESULTS: With regard to efficacy, our meta-analyses demonstrated that anti-VEGF biosimilars for neovascular AMD resulted in little to no difference compared with the reference products for BCVA change at 8 to 12 weeks (MD -0.55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% CI -1.17 to 0.07; 8 studies, 3603 participants; high-certainty evidence) and the proportion of participants who lost fewer than 15 letters in BCVA at 24 to 48 weeks (RR 0.99, 95% CI 0.98 to 1.01; 7 studies, 2658 participants; moderate-certainty evidence). Almost all participants (96.6% in the biosimilar group and 97.0% in the reference product group) lost fewer than 15 letters in BCVA. The evidence from two studies suggested that there was no evidence of difference between biosimilars and reference products in vision-related quality of life measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) summary scores at 24 to 48 weeks (MD 0.82, 95% CI -0.70 to 2.35; 2 studies, 894 participants; moderate-certainty evidence). With regard to the safety profile, meta-analyses also revealed little to no difference between anti-VEGF biosimilars and the reference products for the proportion of participants who experienced serious ocular AEs (RR 1.24, 95% CI 0.68 to 2.26; 7 studies, 3292 participants; moderate-certainty evidence), and for TEAEs leading to investigational product discontinuation or death (RR 0.96, 95% CI 0.63 to 1.46; 8 studies, 3497 participants; moderate-certainty evidence). Overall, 1.4% of participants in the biosimilar group and 1.2% in the reference product group experienced serious ocular adverse events. The most frequently documented serious ocular AEs were retinal hemorrhage and endophthalmitis. Although the evidence is of low certainty due to imprecision, meta-analysis suggested that anti-VEGF biosimilars led to no difference compared with the reference products for cumulative incidence of ADAs (RR 0.84, 95% CI 0.58 to 1.22; 8 studies, 3066 participants; low-certainty evidence) or mean maximum serum concentrations (MD 0.42 ng/mL, 95% CI -0.22 to 1.05; subgroup of 3 studies, 100 participants; low-certainty evidence). We judged the overall risk of bias to be low for all studies.<br><br>AUTHORS' CONCLUSIONS: In our review, low to high certainty evidence suggests that there is little to no difference, to date, between the anti-VEGF biosimilars approved for treating neovascular AMD and their reference products in terms of benefits and harms. While anti-VEGF biosimilars may be a viable alternative to reference products, current evidence for their use is based on a limited number of studies - particularly for comparison with aflibercept - with sparse long-term safety data, and infrequent assessment of quality of life outcomes. Our effect estimates and conclusions may be modified once findings have been reported from studies that are currently ongoing, and studies of biosimilar agents that are currently in development.<br><br>FUNDING: Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. Takeshi Hasegawa and Hisashi Noma were supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239).<br><br>REGISTRATION: Protocol available via doi.org/10.1002/14651858.CD015804.},
}
@article {pmid38829028,
year = {2024},
author = {Thinggaard, BS and Pedersen, F and Kawasaki, R and Wied, J and Subhi, Y and Grauslund, J and Stokholm, L},
title = {Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study.},
journal = {Acta ophthalmologica},
volume = {102},
number = {8},
pages = {953-962},
doi = {10.1111/aos.16727},
pmid = {38829028},
issn = {1755-3768},
mesh = {Humans ; *Endophthalmitis/epidemiology/diagnosis ; *Intravitreal Injections ; Female ; Male ; *Registries ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Incidence ; Denmark/epidemiology ; Risk Factors ; Middle Aged ; Ranibizumab/administration &amp; dosage ; Retrospective Studies ; Follow-Up Studies ; Adult ; Aged, 80 and over ; Risk Assessment/methods ; Bevacizumab/administration &amp; dosage ; },
abstract = {PURPOSE: To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF).<br><br>METHODS: We employed nationwide registries in Denmark to include all individuals aged &#x2265;40&#x2009;years who received at least one intravitreal anti-VEGF injection in 2007-2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10&#x2009;days prior to and 120&#x2009;days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients.<br><br>RESULTS: We identified 60&#x2009;825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2&#x2009;years and females constituting 58.1%. We identified 232 cases of PIE after 1&#x2009;051&#x2009;549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%-0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%-0.023%] from 2013 to 2022. Compared to patients receiving 1-3 injections, RR for patients receiving 4-20, 21-40, and >40 injections were 0.46 [95% CI 0.34-0.63], 0.32 [95% CI 0.21-0.50], and 0.54 [95% CI 0.36-0.81], respectively. Findings were similar across the different diagnoses.<br><br>CONCLUSIONS: Based on 16&#x2009;years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.},
}
@article {pmid38828456,
year = {2024},
author = {Yu, Y and Wang, G and Liu, Y and Meng, Z},
title = {Potential application of traditional Chinese medicine in age-related macular degeneration-focusing on mitophagy.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1410998},
pmid = {38828456},
issn = {1663-9812},
abstract = {Retinal pigment epithelial cell and neuroretinal damage in age-related macular degeneration (AMD) can lead to serious visual impairments and blindness. Studies have shown that mitophagy, a highly specialized cellular degradation system, is implicated in the pathogenesis of AMD. Mitophagy selectively eliminates impaired or non-functioning mitochondria via several pathways, such as the phosphatase and tensin homolog-induced kinase 1/Parkin, BCL2-interacting protein 3 and NIP3-like protein X, FUN14 domain-containing 1, and AMP-activated protein kinase pathways. This has a major impact on the maintenance of mitochondrial homeostasis. Therefore, the regulation of mitophagy could be a promising therapeutic strategy for AMD. Traditional Chinese medicine (TCM) uses natural products that could potentially prevent and treat various diseases, such as AMD. This review aims to summarize recent findings on mitophagy regulation pathways and the latest progress in AMD treatment targeting mitophagy, emphasizing methods involving TCM.},
}
@article {pmid38827773,
year = {2024},
author = {Quah, NQX and Javed, KMAA and Arbi, L and Hanumunthadu, D},
title = {Real-World Outcomes of Faricimab Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {1479-1490},
pmid = {38827773},
issn = {1177-5467},
abstract = {PURPOSE: The purpose of this study was to assess preliminary real-world outcomes in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) treated with intravitreal faricimab.<br><br>PATIENTS AND METHODS: This was a retrospective, observational consecutive-case real-world study of patients with nAMD or DME initiated on intravitreal faricimab between November 2022 and April 2023. Treatment-na&#xef;ve patients and patients previously treated with alternate anti-vascular endothelial growth factor (anti-VEGF) agents were initiated on an intended treatment plan of four monthly faricimab injections as a loading regime. Efficacy was assessed across four treatment groups. Primary outcomes assessed for both cohorts were changes in best corrected visual acuity (BCVA) and central subfield thickness (CST) on optical coherence tomography (OCT). Secondary outcomes were alterations in OCT-defined structural features.<br><br>RESULTS: From 127 patients, 146 eyes received at least one dose of faricimab. Mean BCVA, measured in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, from baseline to fifth visit increased from: 59.0&#xb1;12.8 to 62.2&#xb1;14.3 in treatment-na&#xef;ve nAMD; 61.1&#xb1;17.6 to 63.5&#xb1;14.8 in previously-treated nAMD; 61.1&#xb1;13.0 to 72.8&#xb1;11.5 in treatment-na&#xef;ve DME; and 60.8&#xb1;14.6 to 63.3&#xb1;15.6 in previously-treated DME. Mean CST reduced in all four treatment groups between initiation to final loading dose, from: 442.8&#xb1;172.0&#xb5;m to 305.2&#xb1;117.0&#xb5;m (p<0.0001) in treatment-na&#xef;ve nAMD; 355.2&#xb1;115.1&#xb5;m to 297.9&#xb1;92.54&#xb5;m (p<0.0001) in previously-treated nAMD; 465.8&#xb1;109.1&#xb5;m to 343.1&#xb1;100.3&#xb5;m (p<0.0001) in treatment-na&#xef;ve DME; and 492.5&#xb1;133.1&#xb5;m to 388.5&#xb1;131.4&#xb5;m (p<0.0001) in previously-treated DME.<br><br>CONCLUSION: Real-world outcomes showed some improvement in BCVA and CST for nAMD and DME following faricimab administration, including in patients previously treated with other anti-VEGF agents. Further work involving larger cohorts over longer periods is required to determine whether improvement is maintained, and if intervals can be extended to match those observed in clinical trials.},
}
@article {pmid38827489,
year = {2024},
author = {Sato, Y and Ueda-Arakawa, N and Takahashi, A and Miyake, M and Mori, Y and Miyara, Y and Hara, C and Kitajima, Y and Maruko, R and Kawai, M and Takahashi, H and Koizumi, H and Maruyama-Inoue, M and Yanagi, Y and Iida, T and Takahashi, K and Sakamoto, T and Tsujikawa, A},
title = {Clinical Characteristics and Progression of Pachychoroid and Conventional Geographic Atrophy.},
journal = {Ophthalmology science},
volume = {4},
number = {5},
pages = {100528},
pmid = {38827489},
issn = {2666-9145},
abstract = {PURPOSE: To elucidate the clinical characteristics and progression rates of pachychoroid and conventional geographic atrophy (GA).<br><br>DESIGN: Retrospective, multicenter, observational study.<br><br>PARTICIPANTS: A total of 173 eyes from 173 patients (38 eyes with pachychoroid GA and 135 with conventional GA) from 6 university hospitals in Japan were included. All patients were Japanese, aged &#x2265;50 years and with fundus autofluorescence images having analyzable image quality. A total of 101 eyes (22 with pachychoroid GA and 79 with conventional GA) were included in the follow-up group.<br><br>METHODS: The studied eyes were classified as having pachychoroid or conventional GA; the former was diagnosed if the eye had features of pachychoroid and no drusen. The GA area was semiautomatically measured on fundus autofluorescence images, and the GA progression rate was calculated for the follow-up group. Multivariable linear regression analysis was used to determine whether the rate of GA progression was associated with GA subtype.<br><br>MAIN OUTCOME MEASURES: Clinical characteristics and progression rates of pachychoroid and conventional GA.<br><br>RESULTS: The pachychoroid GA group was significantly younger (70.3 vs. 78.7 years; P < 0.001), more male-dominant (89.5 vs. 55.6%; P < 0.001), and had better best-corrected visual acuity (0.15 vs. 0.40 in logarithm of the minimum angle of resolution; P&#xa0;=&#xa0;0.002), thicker choroid (312.4 vs. 161.6 &#x3bc;m; P < 0.001), higher rate of unifocal GA type (94.7 vs. 49.6%; P < 0.001), and smaller GA area (0.59 vs. 3.76 mm[2;]P < 0.001) than the conventional GA group. In the follow-up group, the mean GA progression rate (square-root transformation) was&#xa0;significantly lower in the pachychoroid GA group than in the conventional GA group (0.11 vs. 0.27 mm/year; P&#xa0;< 0.001).<br><br>CONCLUSIONS: Demographic and ocular characteristics differed between GA subtypes. The progression rate of pachychoroid GA, adjusted for age and baseline GA area, was significantly lower than that of conventional GA. Japanese patients with conventional GA showed characteristics and progression rates similar to those in White populations. Some characteristics of GA in Japanese population differ from those in Waucasian populations, which may be due to the inclusion of pachychoroid GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38826751,
year = {2024},
author = {Prenner, V and Schmidt-Erfurth, U and Fuchs, P and Leingang, O and Coulibaly, LM and Bogunovic, H and Barthelmes, D and Reiter, GS},
title = {Dynamics and patterns of recurrence in neovascular AMD during real-world management using automated fluid monitoring.},
journal = {Heliyon},
volume = {10},
number = {10},
pages = {e31567},
pmid = {38826751},
issn = {2405-8440},
abstract = {In this retrospective longitudinal observational study, data from one site of the Fight Retinal Blindness! Registry (University of Zurich, Switzerland) was used to investigate the quantity and distribution of recurrent fluid in neovascular age-related macular degeneration (nAMD). Study eye eligibility required treatment-naïve nAMD, receiving at least three anti-vascular endothelial growth factor injections, followed by a treatment discontinuation of at least six months and subsequence fluid recurrence. To quantify fluid, a regulatory approved deep learning algorithm (Vienna Fluid Monitor, RetInSight, Vienna, Austria) was used. Fifty-six eyes of 56 patients with a mean age of 76.29 ± 6.58 years at baseline fulfilled the inclusion criteria. From baseline to the end of the first treatment-free interval, SRF volume had decreased significantly (58.0 nl (IQR 10-257 nl) to 8.73 nl (IQR 1-100 nl), p < 0.01). The quantitative increase in IRF volume from baseline to the end of the first treatment-free interval was not statistically significant (1.35 nl (IQR 0-107 nl) to 5.18 nl (IQR 0-24 nl), p = 0.13). PED also did not reach statistical significance (p = 0.71). At the end of the second treatment discontinuation there was quantitatively more IRF (17.3 nl) than SRF (3.74 nl). In conclusion, discontinuation of treatment with anti-VEGF therapy may change the fluid pattern in nAMD.},
}
@article {pmid38826012,
year = {2024},
author = {Velmurugan, S and Pauline, R and Chandrashekar, G and Kulanthaivel, L and Subbaraj, GK},
title = {Understanding the Impact of the Sirtuin 1 (SIRT1) Gene on Age-related Macular Degeneration: A Comprehensive Study.},
journal = {The Nigerian postgraduate medical journal},
volume = {31},
number = {2},
pages = {93-101},
doi = {10.4103/npmj.npmj_9_24},
pmid = {38826012},
issn = {1117-1936},
mesh = {Humans ; *Sirtuin 1/genetics ; *Macular Degeneration/genetics/epidemiology ; Genetic Predisposition to Disease ; Polymorphism, Genetic ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent and incurable condition affecting the central retina and posing a significant risk to vision, particularly in individuals over the age of 60. As the global population ages, the prevalence of AMD is expected to rise, leading to substantial socioeconomic impacts and increased healthcare costs. The disease manifests primarily in two forms, neovascular and non-neovascular, with genetic, environmental and lifestyle factors playing a pivotal role in disease susceptibility and progression. This review article involved conducting an extensive search across various databases, including Google Scholar, PubMed, Web of Science, ScienceDirect, Scopus and EMBASE, to compile relevant case-control studies and literature reviews from online published articles extracted using search terms related to the work. SIRT1, a key member of the sirtuin family, influences cellular processes such as ageing, metabolism, DNA repair and stress response. Its dysregulation is linked to retinal ageing and ocular conditions like AMD. This review discusses the role of SIRT1 in AMD pathology, its association with genetic variants and its potential as a biomarker, paving the way for targeted interventions and personalised treatment strategies. In addition, it highlights the findings of case-control studies investigating the relationship between SIRT1 gene polymorphisms and AMD risk. These studies collectively revealed a significant association between certain SIRT1 gene variants and AMD risk. Further studies with larger sample sizes are required to validate these findings. As the prevalence of AMD grows, understanding the role of SIRT1 and other biomarkers becomes increasingly vital for improving diagnosis, treatment and, ultimately, patient outcomes.},
}
@article {pmid38824253,
year = {2024},
author = {Leitch, IM and Gerometta, M and Eichenbaum, D and Finger, RP and Steinle, NC and Baldwin, ME},
title = {Vascular Endothelial Growth Factor C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular Age-Related Macular Degeneration: A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {7},
pages = {1857-1875},
pmid = {38824253},
issn = {2193-8245},
abstract = {The development of treatments targeting the vascular endothelial growth factor (VEGF) signaling pathways have traditionally been firstly investigated in oncology and then advanced into retinal disease indications. Members of the VEGF family of endogenous ligands and their respective receptors play a central role in vasculogenesis and angiogenesis during both development and physiological homeostasis. They can also play a pathogenic role in cancer and retinal diseases. Therapeutic approaches have mostly focused on targeting VEGF-A signaling; however, research has shown that VEGF-C and VEGF-D signaling pathways are also important to the disease pathogenesis of tumors and retinal diseases. This review highlights the important therapeutic advances and the remaining unmet need for improved therapies targeting additional mechanisms beyond VEGF-A. Additionally, it provides an overview of alternative VEGF-C and VEGF-D signaling involvement in both health and disease, highlighting their key contributions in the multifactorial pathophysiology of retinal disease including neovascular age-related macular degeneration (nAMD). Strategies for targeting VEGF-C/-D signaling pathways will also be reviewed, with an emphasis on agents currently being developed for the treatment of nAMD.},
}
@article {pmid38824126,
year = {2024},
author = {Zhou, S and Taskintuna, K and Hum, J and Gulati, J and Olaya, S and Steinman, J and Golestaneh, N},
title = {PGC-1α repression dysregulates lipid metabolism and induces lipid droplet accumulation in retinal pigment epithelium.},
journal = {Cell death &amp; disease},
volume = {15},
number = {6},
pages = {385},
pmid = {38824126},
issn = {2041-4889},
support = {P30 CA051008/CA/NCI NIH HHS/United States ; R01 EY028917/EY/NEI NIH HHS/United States ; R01EY028917//U.S. Department of Health &amp; Human Services | NIH | National Eye Institute (NEI)/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism ; *Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics ; Animals ; *Lipid Metabolism ; Humans ; Mice ; *Lipid Droplets/metabolism ; *Macular Degeneration/metabolism/pathology/genetics ; Mice, Inbred C57BL ; Mitochondria/metabolism ; Male ; Oxidative Stress ; },
abstract = {Drusen, the yellow deposits under the retina, are composed of lipids and proteins, and represent a hallmark of age-related macular degeneration (AMD). Lipid droplets are also reported in the retinal pigment epithelium (RPE) from AMD donor eyes. However, the mechanisms underlying these disease phenotypes remain elusive. Previously, we showed that Pgc-1α repression, combined with a high-fat diet (HFD), induce drastic AMD-like phenotypes in mice. We also reported increased PGC-1α acetylation and subsequent deactivation in the RPE derived from AMD donor eyes. Here, through a series of in vivo and in vitro experiments, we sought to investigate the molecular mechanisms by which PGC-1α repression could influence RPE and retinal function. We show that PGC-1α plays an important role in RPE and retinal lipid metabolism and function. In mice, repression of Pgc-1α alone induced RPE and retinal degeneration and drusen-like deposits. In vitro inhibition of PGC1A by CRISPR-Cas9 gene editing in human RPE (ARPE19- PGC1A KO) affected the expression of genes responsible for lipid metabolism, fatty acid β-oxidation (FAO), fatty acid transport, low-density lipoprotein (LDL) uptake, cholesterol esterification, cholesterol biosynthesis, and cholesterol efflux. Moreover, inhibition of PGC1A in RPE cells caused lipid droplet accumulation and lipid peroxidation. ARPE19-PGC1A KO cells also showed reduced mitochondrial biosynthesis, impaired mitochondrial dynamics and activity, reduced antioxidant enzymes, decreased mitochondrial membrane potential, loss of cardiolipin, and increased susceptibility to oxidative stress. Our data demonstrate the crucial role of PGC-1α in regulating lipid metabolism. They provide new insights into the mechanisms involved in lipid and drusen accumulation in the RPE and retina during aging and AMD, which may pave the way for developing novel therapeutic strategies targeting PGC-1α.},
}
@article {pmid38822684,
year = {2024},
author = {Bikbov, MM and Kazakbaeva, GM and Rakhimova, EM and Panda-Jonas, S and Fakhretdinova, AA and Tuliakova, AM and Rusakova, IA and Jonas, JB},
title = {Atrial fibrillation and flutter and ocular diseases. The Ural eye and medical study and the Ural very old study.},
journal = {Acta ophthalmologica},
volume = {102},
number = {7},
pages = {e1057-e1065},
doi = {10.1111/aos.16726},
pmid = {38822684},
issn = {1755-3768},
mesh = {Humans ; Male ; Female ; *Atrial Flutter/epidemiology/diagnosis/physiopathology ; Aged ; *Atrial Fibrillation/epidemiology/physiopathology/diagnosis ; Middle Aged ; Prevalence ; Aged, 80 and over ; *Eye Diseases/epidemiology/diagnosis ; Adult ; Risk Factors ; Age Distribution ; Cross-Sectional Studies ; Russia/epidemiology ; },
abstract = {PURPOSE: To assess associations between atrial fibrillation/atrial flutter (AF) and ocular parameters and diseases.<br><br>METHODS: The population-based Ural Eye and Medical Study (UEMS) and the Ural Very Old Study (UVOS) included 4894 individuals (age: 40+ years) and 835 individuals (age: 85+ years), respectively.<br><br>RESULTS: In the UEMS, AF prevalence (80/4894; 1.6%; 95% CI: 1.3, 2.0) increased from 1/1029 (0.1%) in the age group of 40 to <50&#x2009;years to 29/619 (4.7%) and 12/159 (7.5%) in the age groups of 70 to <80&#x2009;years and 80+ years, respectively. Higher AF prevalence correlated with older age (OR: 1.08; 95% CI: 1.04, 1.12; p&#x2009;<&#x2009;0.001), urban region of habitation (OR: 1.08; 95% CI: 1.04, 1.12; p&#x2009;<&#x2009;0.001), higher prevalence of cardiovascular disease/stroke (OR: 2.50; 95% CI: 1.32, 4.72; p&#x2009;<&#x2009;0.001) and lower prevalence of neck pain (OR: 0.35; 95% CI: 0.14, 0.85; p&#x2009;=&#x2009;0.02), higher serum concentration of bilirubin (OR: 1.03; 95% CI: 1.02, 1.05; p&#x2009;<&#x2009;0.001) and lower prothrombin index (OR: 0.96; 95% CI: 0.93, 0.99; p&#x2009;=&#x2009;0.003), higher stage of arterial hypertension (OR: 1.52; 95% CI: 1.01, 2.28; p&#x2009;=&#x2009;0.04) and higher ankle-brachial index (OR: 22.1; 95% CI: 4.45, 1.10; p&#x2009;<&#x2009;0.001). In that model, AF prevalence was not associated with ocular parameters such as intraocular pressure (p&#x2009;=&#x2009;0.52), retinal nerve fibre layer thickness (p&#x2009;=&#x2009;0.70), refractive error (p&#x2009;=&#x2009;0.13), axial length (p&#x2009;=&#x2009;0.14), nuclear cataract degree (p&#x2009;=&#x2009;0.50) and prevalence (p&#x2009;=&#x2009;0.40), cortical cataract degree (p&#x2009;=&#x2009;0.43) and presence (p&#x2009;=&#x2009;0.17), lens pseudoexfoliation (p&#x2009;=&#x2009;0.58), status after cataract surgery (p&#x2009;=&#x2009;0.38), age-related macular degeneration prevalence (p&#x2009;=&#x2009;0.63), open-angle glaucoma presence (p&#x2009;=&#x2009;0.90) and stage (p&#x2009;=&#x2009;0.55), angle-closure glaucoma prevalence (p&#x2009;=&#x2009;0.99) and stage (p&#x2009;=&#x2009;0.99), diabetic retinopathy prevalence presence (p&#x2009;=&#x2009;0.37) and stage (p&#x2009;=&#x2009;0.32), and myopic macular degeneration (p&#x2009;=&#x2009;0.98). In the UVOS, similar results were obtained.<br><br>CONCLUSIONS: In these multi-ethnic populations from Russia, AF prevalence was not associated with any major ocular disease and may not play a major role in the pathogenesis of these disorders.},
}
@article {pmid38822033,
year = {2024},
author = {Calanni, JS and Aranda, ML and Dieguez, HH and Dorfman, D and Schmidt, TM and Rosenstein, RE},
title = {An ethologically relevant paradigm to assess defensive response to looming visual contrast stimuli.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {12499},
pmid = {38822033},
issn = {2045-2322},
support = {PICT 0415, PICT 0157, PICT 1506//Agencia Nacional de Promoci&#xf3;n Cient&#xed;fica y Tecnol&#xf3;gica/ ; PIP 12320220100606CO//Consejo Nacional de Investigaciones Cient&#xed;ficas y T&#xe9;cnicas/ ; R01 EY030565/EY/NEI NIH HHS/United States ; DP2 EY022584 ; R01 EY030565//National Institute of Health, United States/ ; 20020220100070BA//Universidad de Buenos Aires/ ; U10 EY022584/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Rats ; Mice ; Male ; *Retinal Ganglion Cells/physiology ; *Photic Stimulation ; Female ; Contrast Sensitivity/physiology ; Behavior, Animal/physiology ; Retinal Cone Photoreceptor Cells/physiology ; Mice, Inbred C57BL ; Visual Perception/physiology ; Fear/physiology ; Retina/physiology ; Visual Pathways/physiology ; },
abstract = {In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones > > rods > > > ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.},
}
@article {pmid38821570,
year = {2024},
author = {Niestrata, M and Deeks, JJ and Takwoingi, Y and Sivaprasad, S and Patel, PJ and Keane, PA and Kernohan, A and Vale, L and Denniston, AK and Gale, R and Khan, AR and McKinnon, W and Agarwal, R and de Salvo, G and Minos, E and Barbeiro, P and Chakravarthy, U and Waheed, NK and Madhusudhan, S and Peto, T and Balaskas, K},
title = {Study protocol: optical coherence tomography angiography for the detection of neovascular age-related macular degeneration: a comprehensive multicentre diagnostic accuracy study in the UK-the ATHENA study.},
journal = {BMJ open},
volume = {14},
number = {5},
pages = {e070857},
pmid = {38821570},
issn = {2044-6055},
mesh = {Humans ; Choroidal Neovascularization/diagnostic imaging/diagnosis ; *Fluorescein Angiography/methods ; Macular Degeneration/diagnostic imaging ; Multicenter Studies as Topic ; Prospective Studies ; Randomized Controlled Trials as Topic ; *Tomography, Optical Coherence/methods ; United Kingdom ; Wet Macular Degeneration/diagnostic imaging/diagnosis ; },
abstract = {INTRODUCTION: The diagnosis of neovascular age-related macular degeneration (nAMD), the leading cause of visual impairment in the developed world, relies on the interpretation of various imaging tests of the retina. These include invasive angiographic methods, such as Fundus Fluorescein Angiography (FFA) and, on occasion, Indocyanine-Green Angiography (ICGA). Newer, non-invasive imaging modalities, predominately Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA), have drastically transformed the diagnostic approach to nAMD. The aim of this study is to undertake a comprehensive diagnostic accuracy assessment of the various imaging modalities used in clinical practice for the diagnosis of nAMD (OCT, OCTA, FFA and, when a variant of nAMD called Polypoidal Choroidal Vasculopathy is suspected, ICGA) both alone and in various combinations.<br><br>METHODS AND ANALYSIS: This is a non-inferiority, prospective, randomised diagnostic accuracy study of 1067 participants. Participants are patients with clinical features consistent with nAMD who present to a National Health Service secondary care ophthalmology unit in the UK. Patients will undergo OCT as per standard practice and those with suspicious features of nAMD on OCT will be approached for participation in the study. Patients who agree to take part will also undergo both OCTA and FFA (and ICGA if indicated). Interpretation of the imaging tests will be undertaken by clinicians at recruitment sites. A randomised design was selected to avoid bias from consecutive review of all imaging tests by the same clinician. The primary outcome of the study will be the difference in sensitivity and specificity between OCT+OCTA&#x2009;and OCT+FFA (&#xb1;ICGA) for nAMD detection as interpreted by clinicians at recruitment sites.<br><br>ETHICS AND DISSEMINATION: The study has been approved by the South Central-Oxford B Research Ethics Committee with reference number 21/SC/0412.Dissemination of study results will involve peer-review publications, presentations at major national and international scientific conferences.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN18313457.},
}
@article {pmid38820665,
year = {2024},
author = {Wang, D and Chen, Y and Li, J and Wu, E and Tang, T and Singla, RK and Shen, B and Zhang, M},
title = {Natural products for the treatment of age-related macular degeneration.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {130},
number = {},
pages = {155522},
doi = {10.1016/j.phymed.2024.155522},
pmid = {38820665},
issn = {1618-095X},
mesh = {*Macular Degeneration/drug therapy ; Humans ; *Biological Products/pharmacology/therapeutic use ; *Oxidative Stress/drug effects ; Animals ; Phytotherapy ; Vitamin A ; Retina/drug effects ; Phenols/pharmacology/therapeutic use ; Functional Food ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly.<br><br>PURPOSE: There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking.<br><br>STUDY DESIGN AND METHODS: PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods.<br><br>RESULTS: The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies.<br><br>CONCLUSION: Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease.},
}
@article {pmid38819490,
year = {2024},
author = {Yamashita, T and Terasaki, H and Asaoka, R and Iwase, A and Sakai, H and Sakamoto, T and Araie, M},
title = {Age prediction using fundus parameters of normal eyes from the Kumejima population study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {10},
pages = {3393-3401},
pmid = {38819490},
issn = {1435-702X},
support = {21H03095//Japan Society for the Promotion of Science/ ; JP17591845//Japan Society for the Promotion of Science/ ; JP21K09704//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; *Fundus Oculi ; Aged ; *Aging/physiology ; Adult ; *Optic Disk/anatomy &amp; histology/diagnostic imaging ; Japan ; Retinal Vessels/diagnostic imaging ; Healthy Volunteers ; Population Surveillance ; Photography/methods ; },
abstract = {PURPOSE: Artificial intelligence can predict the age of an individual using color fundus photographs (CFPs). This study aimed to investigate the accuracy of age prediction in the Kumejima study using fundus parameters and to clarify age-related changes in the fundus.<br><br>METHODS: We used nonmydriatic CFPs obtained from the Kumejima population study, including 1,646 right eyes of healthy participants with reliable fundus parameter measurements. The tessellation fundus index was calculated as R/(R&#x2009;+&#x2009;G&#x2009;+&#x2009;B) using the mean value of the red-green-blue intensity in eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. Least absolute shrinkage and selection operator regression with leave-one-out cross-validation was used to predict age. The relationship between the actual and predicted ages was investigated using Pearson's correlation coefficient.<br><br>RESULTS: The mean age of included participants (834 males and 812 females) was 53.4&#x2009;&#xb1;&#x2009;10.1&#xa0;years. The mean predicted age based on fundus parameters was 53.4&#x2009;&#xb1;&#x2009;8.9&#xa0;years, with a mean absolute error of 3.64&#xa0;years, and the correlation coefficient between actual and predicted age was 0.88 (p&#x2009;<&#x2009;0.001). Older patients had greater red and green intensities and weaker blue intensities in the peripapillary area (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Age could be predicted using the CFP parameters, and there were notable age-related changes in the peripapillary color intensity. The age-related changes in the fundus may aid the understanding of the mechanism of fundus diseases such as age-related macular degeneration.},
}
@article {pmid38819041,
year = {2025},
author = {Zhang, J and Sheng, X and Ding, Q and Wang, Y and Zhao, J and Zhang, J},
title = {Subretinal fibrosis secondary to neovascular age-related macular degeneration: mechanisms and potential therapeutic targets.},
journal = {Neural regeneration research},
volume = {20},
number = {2},
pages = {378-393},
pmid = {38819041},
issn = {1673-5374},
abstract = {Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration. It causes local damage to photoreceptors, retinal pigment epithelium, and choroidal vessels, which leads to permanent central vision loss of patients with neovascular age-related macular degeneration. The pathogenesis of subretinal fibrosis is complex, and the underlying mechanisms are largely unknown. Therefore, there are no effective treatment options. A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments. The current article reviews several aspects of subretinal fibrosis, including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis; multimodal imaging techniques for subretinal fibrosis; animal models for studying subretinal fibrosis; cellular and non-cellular constituents of subretinal fibrosis; pathophysiological mechanisms involved in subretinal fibrosis, such as aging, infiltration of macrophages, different sources of mesenchymal transition to myofibroblast, and activation of complement system and immune cells; and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis, such as vascular endothelial growth factor, connective tissue growth factor, fibroblast growth factor 2, platelet-derived growth factor and platelet-derived growth factor receptor-β, transforming growth factor-β signaling pathway, Wnt signaling pathway, and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10. This review will improve the understanding of the pathogenesis of subretinal fibrosis, allow the discovery of molecular targets, and explore potential treatments for the management of subretinal fibrosis.},
}
@article {pmid38819040,
year = {2025},
author = {Abokyi, S and Tse, DY},
title = {Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy.},
journal = {Neural regeneration research},
volume = {20},
number = {2},
pages = {366-377},
pmid = {38819040},
issn = {1673-5374},
abstract = {Retinal aging has been recognized as a significant risk factor for various retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma, following a growing understanding of the molecular underpinnings of their development. This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches, focusing on the activation of transcription factor EB. Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies, such as exercise, calorie restriction, rapamycin, and metformin, in patients and animal models of these common retinal diseases. The review critically assesses the role of transcription factor EB in retinal biology during aging, its neuroprotective effects, and its therapeutic potential for retinal disorders. The impact of transcription factor EB on retinal aging is cell-specific, influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways. In vascular endothelial cells, transcription factor EB controls important processes, including endothelial cell proliferation, endothelial tube formation, and nitric oxide levels, thereby influencing the inner blood-retinal barrier, angiogenesis, and retinal microvasculature. Additionally, transcription factor EB affects vascular smooth muscle cells, inhibiting vascular calcification and atherogenesis. In retinal pigment epithelial cells, transcription factor EB modulates functions such as autophagy, lysosomal dynamics, and clearance of the aging pigment lipofuscin, thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization. These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis, neuronal synapse plasticity, energy metabolism, microvasculature, and inflammation, ultimately offering protection against retinal aging and diseases. The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases. Therefore, it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.},
}
@article {pmid38816934,
year = {2024},
author = {Kwon, YS and Munsoor, J and Kaufmann, M and Zheng, M and Smirnov, AI and Han, Z},
title = {Polydopamine Nanoparticles as Mimicking RPE Melanin for the Protection of Retinal Cells Against Blue Light-Induced Phototoxicity.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {11},
number = {29},
pages = {e2400230},
pmid = {38816934},
issn = {2198-3844},
support = {T35 AG038047/AG/NIA NIH HHS/United States ; M2022001F//BrightFocus Foundation/ ; 138298//Edward N. and Della L. Thome Memorial Foundation/ ; },
mesh = {Animals ; Mice ; *Blue Light/adverse effects ; Disease Models, Animal ; *Indoles/pharmacology ; Macular Degeneration/metabolism/prevention &amp; control ; *Melanins/metabolism ; Nanoparticles ; *Polymers/pharmacology/chemistry ; *Reactive Oxygen Species/metabolism ; Retina/drug effects/radiation effects/metabolism ; *Retinal Pigment Epithelium/drug effects/metabolism/radiation effects ; },
abstract = {Exposure of the eyes to blue light can induce the overproduction of reactive oxygen species (ROS) in the retina and retinal pigment epithelium (RPE) cells, potentially leading to pathological damage of age-related macular degeneration (AMD). While the melanin in RPE cells absorbs blue light and prevents ROS accumulation, the loss and dysfunction of RPE melanin due to age-related changes may contribute to photooxidation toxicity. Herein, a novel approach utilizing a polydopamine-replenishing strategy via a single-dose intravitreal (IVT) injection is presented to protect retinal cells against blue light-induced phototoxicity. To investigate the effects of overexposure to blue light on retinal cells, a blue light exposure Nrf2-deficient mouse model is created, which is susceptible to light-induced retinal lesions. After blue light irradiation, retina degeneration and an overproduction of ROS are observed. The polydopamine-replenishing strategy demonstrated effectiveness in maintaining retinal structural integrity and preventing retina degeneration by reducing ROS production in retinal cells and limiting the phototoxicity of blue light exposure. These findings highlight the potential of polydopamine as a simple and effective replenishment for providing photoprotection against high-energy blue light exposure.},
}
@article {pmid38815954,
year = {2025},
author = {Lindenberg, S and Nittala, MG and Verma, A and Fitzgerald, MEC and Velaga, SB and Bhisitkul, RB and Sadda, SR},
title = {Subretinal hyperreflective material in regions of atrophy and fibrosis in eyes with neovascular age-related macular degeneration.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {1},
pages = {26-34},
doi = {10.1016/j.jcjo.2024.05.007},
pmid = {38815954},
issn = {1715-3360},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Angiogenesis Inhibitors/therapeutic use ; Atrophy ; Cross-Sectional Studies ; Fibrosis ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Ranibizumab/therapeutic use ; *Retina/pathology ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {BACKGROUND: Subretinal hyperreflective material (SHRM) is a significant biomarker for poor visual outcomes in neovascular age-related macular degeneration (nAMD); however, its relationship with fibrosis and atrophy is not well understood. This study aims to evaluate the relationship between SHRM, atrophy, and fibrosis in eyes receiving antivascular endothelial growth factor therapy for nAMD.<br><br>METHODS: Post-hoc analysis of the 65 patients enrolled in the SEVEN-UP study, a multicenter cross-sectional study of patients originally enrolled in the ANCHOR and MARINA trials of ranibizumab. Color fundus photographs (CFP) were reviewed and manually segmented to define regions of atrophy and fibrosis. SHRM borders on OCT volume scans were manually delineated, and thickness measurements were computed and compared in corresponding regions of atrophy and fibrosis on the CFPs.<br><br>RESULTS: Of the 65 subjects, 51 eyes showed atrophy and/or fibrosis on CFP and were included in the final analysis. Both atrophy and fibrosis regions exhibited SHRM on OCT. The mean SHRM thickness on OCT was significantly greater in CFP-fibrosis regions (44.19 &#xb1; 46.95 &#x3bc;m) compared with CFP-atrophy regions (14.28 &#xb1; 13.35 &#x3bc;m; p < 0.001). Additionally, the average maximum height of SHRM in fibrotic regions (268.04 &#xb1; 130.05 &#x3bc;m) was significantly thicker than in atrophic regions (121.95 &#xb1; 51.17 &#x3bc;m; p < 0.001).<br><br>CONCLUSIONS: Although atrophy and fibrosis are thought to be different end-stage outcomes in eyes with nAMD, they both demonstrate SHRM on OCT; the main distinction being thickness. Given these similarities, these regions of nAMD-associated atrophy may be better-termed "atrosis" to distinguish these lesions from typical atrophy in the absence of neovascular disease.},
}
@article {pmid38815899,
year = {2024},
author = {Picard, E and Youale, J and Hyman, MJ and Xie, E and Achiedo, S and Kaufmann, GT and Moir, J and Daruich, A and Crisanti, P and Torriglia, A and Polak, M and Behar-Cohen, F and Skondra, D and Berdugo, M},
title = {Glyburide confers neuroprotection against age-related macular degeneration (AMD).},
journal = {Translational research : the journal of laboratory and clinical medicine},
volume = {272},
number = {},
pages = {81-94},
doi = {10.1016/j.trsl.2024.05.002},
pmid = {38815899},
issn = {1878-1810},
mesh = {Humans ; *Glyburide/pharmacology/therapeutic use ; *Macular Degeneration/drug therapy/prevention &amp; control ; *Neuroprotective Agents/therapeutic use/pharmacology ; *Oxidative Stress/drug effects ; Male ; Female ; Apoptosis/drug effects ; Aged ; Cell Line ; Case-Control Studies ; Retinal Cone Photoreceptor Cells/drug effects/pathology ; Neuroprotection/drug effects ; Inflammasomes/metabolism/drug effects ; },
abstract = {Glyburide, a sulfonylurea drug used to treat type 2 diabetes, boasts neuroprotective effects by targeting the sulfonylurea receptor 1 (SUR1) and associated ion channels in various cell types, including those in the central nervous system and the retina. Previously, we demonstrated that glyburide therapy improved retinal function and structure in a rat model of diabetic retinopathy. In the present study, we explore the application of glyburide in non-neovascular ("dry") age-related macular degeneration (AMD), another progressive disease characterized by oxidative stress-induced damage and neuroinflammation that trigger cell death in the retina. We show that glyburide administration to a human cone cell line confers protection against oxidative stress, inflammasome activation, and apoptosis. To corroborate our in vitro results, we also conducted a case-control study, controlling for AMD risk factors and other diabetes medications. It showed that glyburide use in patients reduces the odds of new-onset dry AMD. A positive dose-response relationship is observed from this analysis, in which higher cumulative doses of glyburide further reduce the odds of new-onset dry AMD. In the quest for novel therapies for AMD, glyburide emerges as a promising repurposable drug given its known safety profile. The results from this study provide insights into the multifaceted actions of glyburide and its potential as a neuroprotective agent for retinal diseases; however, further preclinical and clinical studies are needed to validate its therapeutic potential in the context of degenerative retinal disorders such as AMD.},
}
@article {pmid38815872,
year = {2024},
author = {Dennis, DG and Joo Sun, Y and Parsons, DE and Mahajan, VB and Smith, M},
title = {Identification of highly potent and selective HTRA1 inhibitors.},
journal = {Bioorganic &amp; medicinal chemistry letters},
volume = {109},
number = {},
pages = {129814},
pmid = {38815872},
issn = {1464-3405},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; T32 EY027816/EY/NEI NIH HHS/United States ; },
mesh = {*High-Temperature Requirement A Serine Peptidase 1/metabolism ; Structure-Activity Relationship ; Humans ; *Serine Endopeptidases/metabolism ; Serine Proteinase Inhibitors/pharmacology/chemistry/chemical synthesis ; Molecular Structure ; Dose-Response Relationship, Drug ; Small Molecule Libraries/chemistry/pharmacology/chemical synthesis ; },
abstract = {High temperature requirement A serine peptidase 1 (HTRA1) is a serine protease involved in an array of signaling pathways. It is also responsible for the regulation of protein aggregates via refolding, translocation, and degradation. It has subsequently been found that runaway proteolytic HTRA1 activity plays a role in a variety of diseases, including Age-Related Macular Degeneration (AMD), osteoarthritis, and Rheumatoid Arthritis. Selective inhibition of serine protease HTRA1 therefore offers a promising new strategy for the treatment of these diseases. Herein we disclose structure-activity-relationship (SAR) studies which identify key interactions responsible for binding affinity of small molecule inhibitors to HTRA1. The study results in highly potent molecules with IC50's less than 15 nM and excellent selectivity following a screen of 35 proteases.},
}
@article {pmid38814914,
year = {2024},
author = {Sivaprasad, S and Bailey, C and Downey, L and Gilbert, R and Gale, R and Kotagiri, A and Mahmood, S and Morgan-Warren, P and Napier, J and Narendran, N and Pearce, I and Rennie, C and Talks, J and Wojcik, R and Jandhyala, R},
title = {Real-world service costs for neovascular-AMD clinics in the United Kingdom: structured literature review and scenario analysis.},
journal = {Current medical research and opinion},
volume = {40},
number = {7},
pages = {1221-1233},
doi = {10.1080/03007995.2024.2362278},
pmid = {38814914},
issn = {1473-4877},
mesh = {Humans ; United Kingdom ; *Cost-Benefit Analysis ; Health Care Costs/statistics &amp; numerical data ; Angiogenesis Inhibitors/economics/therapeutic use ; },
abstract = {OBJECTIVE: Current cost-effectiveness analyses (CEA) emphasize drug costs as the differentiator between NICE recommended anti-VEGF treatments but may neglect real-world non-drug costs of running nAMD services in the UK. To address this, this study identified real-world non-drug service cost items relevant to UK NHS nAMD clinics, including costs arising from operational strain (demand exceeding capacity).<br><br>METHODS: Cost items were identified by a structured literature review of peer-reviewed and grey literature, and an expert panel of 10 UK-based ophthalmologists with relevance to real-world practice. These items underwent meta-synthesis and were then determined in a consensus exercise.<br><br>RESULTS: Of 237 cost items identified, 217 (91.6%) met the consensus threshold of >0.51 and were included in the nAMD Service Non-Drug Cost Instrument (nAS). Sensitivity of cost items taken from UK Health Technology Assessment (HTA) using the nAS as the reference standard was low (HTAmin: 1.84%, 95% CI 0.50-4.65%; HTAmax: 70.51%, 95% CI 63.96-76.49%). False negative rates showed variable likelihood of misclassifying a service by cost burden depending on prevalence. Scenario analysis using cost magnitudes estimated annual per-patient clinic cost at &#xa3;845 (within capacity) to &#xa3;13,960 (under strain) compared to an HTAmin estimate of &#xa3;210. Accounting for cost of strain under an assumed 50% increase in health resource utilization influenced cost-effectiveness in a hypothetical genericisation scenario.<br><br>CONCLUSION: Findings suggested that HTA underestimates UK NHS nAMD clinic cost burden with cost of strain contributing substantial additional unmeasured expense with impact on CEA. Given potential undertreatment due to strain, durability is suggested as one of the relevant factors in CEA of nAMD anti-VEGF treatments due to robustness under limited capacity conditions affecting UK ophthalmology services.},
}
@article {pmid38814620,
year = {2024},
author = {Voelker, R},
title = {What Is Age-Related Macular Degeneration?.},
journal = {JAMA},
volume = {331},
number = {24},
pages = {2142},
doi = {10.1001/jama.2024.4281},
pmid = {38814620},
issn = {1538-3598},
mesh = {Aged ; Humans ; *Macular Degeneration/diagnosis/physiopathology/therapy ; Risk Factors ; },
}
@article {pmid38813903,
year = {2024},
author = {Jiang, YJ and Lai, PH and Huang, X},
title = {Interhemispheric functional in age-related macular degeneration patient: a resting-state functional MRI study.},
journal = {Neuroreport},
volume = {35},
number = {10},
pages = {621-626},
doi = {10.1097/WNR.0000000000002045},
pmid = {38813903},
issn = {1473-558X},
mesh = {Humans ; *Magnetic Resonance Imaging/methods ; Male ; Female ; *Macular Degeneration/physiopathology/diagnostic imaging ; Aged ; Middle Aged ; Brain/diagnostic imaging/physiopathology ; Brain Mapping/methods ; Rest ; Functional Laterality/physiology ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent disease leading to severe visual impairment in the elderly population. Despite this, the pathogenesis of AMD remains largely unexplored. The application of resting-state functional MRI (rs-fMRI) allows for the detection of coherent intrinsic brain activities along with the interactions taking place between the two hemispheres. In the frame of our study, we utilize voxel-mirrored homotopic connectivity (VMHC) as an rs-fMRI method to carry out a comparative analysis of functional homotopy between the two hemispheres with the aim of further understanding the pathogenesis of AMD patients. In our study, we utilized the VMHC method to explore levels of brain activity in individuals diagnosed with AMD, planning to investigate potential links with their clinical characteristics. We extended our invitation to 20 AMD patients and 20 healthy controls from Jiangxi Provincial People's Hospital to participate in this research. rs-fMRIs were captured for each participant, and associated neural activity levels were examined using the VMHC method. Remarkably, our comparative examination with the healthy control group revealed significantly reduced VMHC in the cuneus, superior occipital lobe, precentral gyrus, and superior parietal lobule in the patient cohort. Utilizing the VMHC method allows us to identify discrepancies in the visual pathways of AMD patients compared with standard controls, potentially explaining the common challenges among AMD patients with object recognition, face recognition, and reading.},
}
@article {pmid38813161,
year = {2024},
author = {Lacramioara, S and Ovidiu, S and Simona, C},
title = {Real-world evidence for brolucizumab efficacy in age-related macular degeneration and central serous chorioretinopathy patients.},
journal = {Heliyon},
volume = {10},
number = {10},
pages = {e31315},
pmid = {38813161},
issn = {2405-8440},
abstract = {Real-world studies concerning different populations are valuable and bring new information regarding different regimens of Brolucizumab injections and their adverse reactions. The present study investigates the efficacy of a pro-re-nata regimen (PRN) for neovascular Age-related Macular Degeneration (nAMD). Separate from the main statistics we report the use of Brolucizumab in central serous chorioretinopathy (CSC). A retrospective observational single-center study was conducted on 82 eyes treated with Brolucizumab between 2021 and 2023, for nAMD. Patients were injected at intervals of at least 2 months after the loading phase. In 9 (3-20) months follow-up, only 0.26 % adverse reactions were noticed, with good resolution of retinal fluid (significant reduction of CST on SD-OCT, -72.50μ, p < 0.05), especially for subretinal fluid. 54 % of the eyes remained fluid-free. The interval of injection (INTOI, a parameter calculated by averaging the results of the division of the follow-up period to the number of injections received by each patient) was 2.68 (corresponding to an injection interval of 11 weeks). This could become an important parameter for the characterization of Brolucizumab and any other anti-VEGF therapy and could provide a more precise interval of injection in the future. Four patients also received Brolucizumab for the treatment of chronic CSC (3 doses each). All showed good response, 3 of them remaining fluid-free.},
}
@article {pmid38812454,
year = {2024},
author = {Goh, KL and Abbott, CJ and Campbell, TG and Cohn, AC and Ong, DN and Wickremasinghe, SS and Hodgson, LAB and Guymer, RH and Wu, Z},
title = {Clinical performance of predicting late age-related macular degeneration development using multimodal imaging.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {7},
pages = {774-782},
doi = {10.1111/ceo.14405},
pmid = {38812454},
issn = {1442-9071},
support = {//Macular Disease Foundation Australia/ ; #2008382//National Health and Medical Research Council/ ; APP1027624//National Health and Medical Research Council/ ; GNT1194667//National Health and Medical Research Council/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Multimodal Imaging ; Male ; Aged ; Female ; *Fluorescein Angiography/methods ; *Photography/methods ; Aged, 80 and over ; Risk Factors ; Disease Progression ; Macular Degeneration/diagnosis/diagnostic imaging ; Predictive Value of Tests ; ROC Curve ; Middle Aged ; Retinal Drusen/diagnosis/diagnostic imaging ; Prospective Studies ; },
abstract = {BACKGROUND: To examine whether the clinical performance of predicting late age-related macular degeneration (AMD) development is improved through using multimodal imaging (MMI) compared to using colour fundus photography (CFP) alone, and how this compares with a basic prediction model using well-established AMD risk factors.<br><br>METHODS: Individuals with AMD in this study underwent MMI, including optical coherence tomography (OCT), fundus autofluorescence, near-infrared reflectance and CFP at baseline, and then at 6-monthly intervals for 3-years to determine MMI-defined late AMD development. Four retinal specialists independently assessed the likelihood that each eye at baseline would progress to MMI-defined late AMD over 3-years with CFP, and then with MMI. Predictive performance with CFP and MMI were compared to each other, and to a basic prediction model using age, presence of pigmentary abnormalities, and OCT-based drusen volume.<br><br>RESULTS: The predictive performance of the clinicians using CFP [AUC&#x2009;=&#x2009;0.75; 95% confidence interval (CI)&#x2009;=&#x2009;0.68-0.82] improved when using MMI (AUC&#x2009;=&#x2009;0.79; 95% CI&#x2009;=&#x2009;0.72-0.85; p&#x2009;=&#x2009;0.034). However, a basic prediction model outperformed clinicians using either CFP or MMI (AUC&#x2009;=&#x2009;0.85; 95% CI&#x2009;=&#x2009;0.78-91; p&#x2009;&#x2264;&#x2009;0.002).<br><br>CONCLUSIONS: Clinical performance for predicting late AMD development was improved by using MMI compared to CFP. However, a basic prediction model using well-established AMD risk factors outperformed retinal specialists, suggesting that such a model could further improve personalised counselling and monitoring of individuals with the early stages of AMD in clinical practice.},
}
@article {pmid38811237,
year = {2024},
author = {Bachmeier, I and Armendariz, BG and Yu, S and Jäger, RJ and Ebneter, A and Glittenberg, C and Pauleikhoff, D and Sadda, SR and Chakravarthy, U and Fauser, S},
title = {Corrigendum to "Fibrosis in neovascular age-related macular degeneration: a review of definitions based on clinical imaging" [Surv Ophthalmol 68 (2023) 835-848/5].},
journal = {Survey of ophthalmology},
volume = {69},
number = {6},
pages = {990},
doi = {10.1016/j.survophthal.2023.10.007},
pmid = {38811237},
issn = {1879-3304},
}
@article {pmid38811051,
year = {2024},
author = {Ritter, M and Hummer, A and Pawloff, M and Ledolter, AA and Linhardt, D and Woletz, M and Deak, GG and Sacu, S and Ristl, R and Ramazanova, D and Holder, GE and Windischberger, C and Schmidt-Erfurth, UM},
title = {Retinotopic cortical mapping in objective functional monitoring of macular therapy.},
journal = {The British journal of ophthalmology},
volume = {109},
number = {1},
pages = {98-106},
doi = {10.1136/bjo-2021-320723},
pmid = {38811051},
issn = {1468-2079},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Female ; *Tomography, Optical Coherence/methods ; *Magnetic Resonance Imaging/methods ; Aged ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Intravitreal Injections ; *Contrast Sensitivity/physiology ; *Visual Field Tests/methods ; Aged, 80 and over ; Visual Cortex/physiopathology/diagnostic imaging ; Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Brain Mapping/methods ; Visual Fields/physiology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Reading ; Middle Aged ; Retina/physiopathology/diagnostic imaging ; },
abstract = {BACKGROUND/AIMS: To determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance.<br><br>METHODS: Twenty patients with neovascular age-related macular degeneration (nAMD) were studied with high-resolution fMRI, visual acuity, reading accuracy and speed, contrast sensitivity (CS) and microperimetry (MP) before and after 3 monthly intravitreal injections of ranibizumab. Population-receptive field retinotopic maps calculated from fMRI data were compared with psychophysical measures and optical coherence tomography.<br><br>RESULTS: Best-corrected visual acuity (BCVA) responders (&#x2265;5 letters) showed an increase of 29.5% in activated brain area, while non-responders showed a decrease of 0.8%. Radial histograms over eccentricity allowed quantification of the absolute number of significant voxels and thus differences before and after treatment. Responders showed increases in foveal (&#x3b1;<0.5&#xb0;) activation, while non-responders did not. Absence of intraretinal fluid and preservation of outer retinal layers was associated with higher numbers of active V1 voxels and better BCVA. Higher voxel numbers were associated with improved reading performance and, less marked, with BCVA, CS and MP.<br><br>CONCLUSION: The data show that retinotopic mapping using fMRI can successfully be applied objectively to evaluate the therapeutic response in nAMD patients treated with anti-vascular endothelial growth factor therapy. This demonstrates the ability of retinotopic mapping to provide an objective assessment of functional recovery at a cortical level; the technique can therefore be applied, in other degenerative macular diseases, to the assessment of potential therapeutic interventions such as gene therapy or cell replacement therapy.},
}
@article {pmid38810762,
year = {2024},
author = {Qu, Y and Jiang, Y and Zhang, G and Luo, H and Hu, W and Wu, Z and Meng, X and Chen, R and Jia, H and Sun, X},
title = {Association of exposure to ultraviolet radiation and warm-season ozone air pollution with incident age-related macular degeneration: A nationwide cohort study in China.},
journal = {The Science of the total environment},
volume = {938},
number = {},
pages = {173580},
doi = {10.1016/j.scitotenv.2024.173580},
pmid = {38810762},
issn = {1879-1026},
mesh = {*Ozone/analysis ; *Ultraviolet Rays ; Humans ; China/epidemiology ; *Macular Degeneration/epidemiology/etiology ; *Air Pollution/statistics &amp; numerical data ; Male ; Female ; *Environmental Exposure/statistics &amp; numerical data ; Aged ; *Air Pollutants ; Middle Aged ; Cohort Studies ; Seasons ; Incidence ; },
abstract = {BACKGROUND: As the leading cause of blindness, age-related macular degeneration (AMD) performs an adverse impact on human health and disability. AMD have been reported to be associated with environmental factors; however, the association between ultraviolet (UV) radiation, warm-season ambient ozone pollution, and incident AMD remains unclear.<br><br>METHODS: In this study, 19,707 participants without AMD at baseline were included from a nationwide longitudinal cohort in China. UV radiation and warm-season ozone exposure were evaluated through satellite-based models. Incident AMD was diagnosed via ophthalmological fundus images. Cox proportional hazard regression models were employed to explore the association of UV radiation and warm-season ozone with incident AMD, and the hazard ratios (HRs) and 95&#xa0;% confidence intervals (CIs) were reported.<br><br>RESULTS: During 312,935 person-month of follow-up, 3774 participants developed to AMD. High exposure to both UV radiation and warm-season ozone was associated with increasing risk of incident AMD, with HRs and 95&#xa0;% CIs of 1.32 (1.23, 1.41) and 1.20 (1.11, 1.29) in two-exposure models, respectively. Moreover, negative interaction between UV radiation and warm-season ozone was identified, and it was found that exposure to high UV radiation and low ozone presented the highest hazard for AMD. Subgroup analyses showed that the UV-AMD association was stronger in southern China, while the ozone-AMD association was greater in northern China and rural areas.<br><br>CONCLUSION: Our study provides the first epidemiological evidence that both UV radiation and warm-season ozone would elevate the risk of incident AMD, and the hazard of higher UV radiation may be attenuated by exposure to ozone. Strategies for decreasing AMD burden should jointly consider environmental exposures and geographic locations.},
}
@article {pmid38809962,
year = {2024},
author = {Marrero, AD and Cárdenas, C and Castilla, L and Ortega-Vidal, J and Quesada, AR and Martínez-Poveda, B and Medina, M&#xc1;},
title = {Antiangiogenic Potential of an Olive Oil Extract: Insights from a Proteomic Study.},
journal = {Journal of agricultural and food chemistry},
volume = {72},
number = {23},
pages = {13023-13038},
pmid = {38809962},
issn = {1520-5118},
mesh = {*Olive Oil/chemistry ; *Proteomics ; Humans ; *Angiogenesis Inhibitors/pharmacology/chemistry ; *Plant Extracts/chemistry/pharmacology ; *Cell Movement/drug effects ; Olea/chemistry ; Endothelial Cells/drug effects/metabolism ; Apoptosis/drug effects ; Spain ; Human Umbilical Vein Endothelial Cells/metabolism/drug effects ; Cell Adhesion/drug effects ; },
abstract = {Extra virgin olive oil (EVOO), a staple of the Mediterranean diet, is rich in phenolic compounds recognized for their potent bioactive effects, including anticancer and anti-inflammatory properties. However, its effects on vascular health remain relatively unexplored. In this study, we examined the impact of a "picual" EVOO extract from Jaén, Spain, on endothelial cells. Proteomic analysis revealed the modulation of angiogenesis-related processes. In subsequent in vitro experiments, the EVOO extract inhibited endothelial cell migration, adhesion, invasion, ECM degradation, and tube formation while inducing apoptosis. These results provide robust evidence of the extract's antiangiogenic potential. Our findings highlight the potential of EVOO extracts in mitigating angiogenesis-related pathologies, such as cancer, macular degeneration, and diabetic retinopathy.},
}
@article {pmid38809658,
year = {2025},
author = {Arrigo, A and Aragona, E and Allamprese, M and Battaglia Parodi, M},
title = {Ophthalmologists' awareness of geographic atrophy: An Italian survey including 365 participants.},
journal = {European journal of ophthalmology},
volume = {35},
number = {1},
pages = {245-251},
pmid = {38809658},
issn = {1724-6016},
mesh = {Humans ; Italy/epidemiology ; *Geographic Atrophy/diagnosis/epidemiology ; *Ophthalmologists/statistics &amp; numerical data ; Surveys and Questionnaires ; Female ; Male ; Middle Aged ; Health Knowledge, Attitudes, Practice ; Aged ; Adult ; },
abstract = {PURPOSE: Geographic atrophy (GA) is a severe complication of age-related macular degeneration (AMD) and leads to irreversible visual decline. To date, no effective treatment is available for GA patients. However, a number of new therapies have recently been approved and several others are in the pipeline. This rapid evolution of prospects for GA patients requires constant updating of ophthalmologists' understanding of GA and its management so as to provide the appropriate treatment. For this reason, Società Italiana di Scienze Oftalmologiche (S.I.S.O.) has designed a specific survey to gauge the position of Italian ophthalmologists in this regard.<br><br>METHODS: The three hundred and sixty-five Italian ophthalmologists who agreed to take part received a seventeen-part questionnaire guaranteeing privacy and anonymity. The survey was compiled through an online portal and the results were sent directly to S.I.S.O. ETS. Two graders analyzed the data and recorded the results.<br><br>RESULTS: The results showed a high level of self-assessed awareness and understanding of GA, as well as considerable willingness to further improve knowledge of the disease. Most of the participants claimed to have effective rules of conduct in place for managing GA patients, including prompt response, involving a high prevalence of nutraceutical prescriptions and lifestyle recommendations.<br><br>CONCLUSIONS: This survey provided an overview of how GA patients are managed in Italy. The Italian ophthalmology community appears to be ready to adopt the upcoming treatments for GA.},
}
@article {pmid38809490,
year = {2024},
author = {Liu, H and Lu, S and Chen, M and Gao, N and Yang, Y and Hu, H and Ren, Q and Liu, X and Chen, H and Zhu, Q and Li, S and Su, J},
title = {Towards Stem/Progenitor Cell-Based Therapies for Retinal Degeneration.},
journal = {Stem cell reviews and reports},
volume = {20},
number = {6},
pages = {1459-1479},
pmid = {38809490},
issn = {2629-3277},
support = {82172882//National Natural Science Foundation of China/ ; 82101143//National Natural Science Foundation of China/ ; LZ24H120003//Zhejiang Provincial Natural Science/ ; LQ24C120003//Zhejiang Provincial Natural Science/ ; },
mesh = {Humans ; *Retinal Degeneration/therapy/pathology ; *Stem Cell Transplantation ; Animals ; Stem Cells/cytology ; Cell- and Tissue-Based Therapy/methods ; Retina/cytology/pathology ; },
abstract = {Retinal degeneration (RD) is a leading cause of blindness worldwide and includes conditions such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt's disease (STGD). These diseases result in the permanent loss of vision due to the progressive and irreversible degeneration of retinal cells, including photoreceptors (PR) and the retinal pigment epithelium (RPE). The adult human retina has limited abilities to regenerate and repair itself, making it challenging to achieve complete self-replenishment and functional repair of retinal cells. Currently, there is no effective clinical treatment for RD. Stem cell therapy, which involves transplanting exogenous stem cells such as retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), or activating endogenous stem cells like Müller Glia (MG) cells, holds great promise for regenerating and repairing retinal cells in the treatment of RD. Several preclinical and clinical studies have shown the potential of stem cell-based therapies for RD. However, the clinical translation of these therapies for the reconstruction of substantial vision still faces significant challenges. This review provides a comprehensive overview of stem/progenitor cell-based therapy strategies for RD, summarizes recent advances in preclinical studies and clinical trials, and highlights the major challenges in using stem/progenitor cell-based therapies for RD.},
}
@article {pmid38808557,
year = {2024},
author = {Xu, M and Gao, Y and Yin, W and Liu, Q and Yuan, S},
title = {RNA-sequencing expression profile and functional analysis of retinal pigment epithelium in atrophic age-related macular degeneration.},
journal = {Journal of biomedical research},
volume = {38},
number = {5},
pages = {500-511},
pmid = {38808557},
issn = {1674-8301},
abstract = {The retinal pigment epithelium (RPE) is fundamental to sustaining retinal homeostasis. RPE abnormality leads to visual defects and blindness, including age-related macular degeneration (AMD). Although breakthroughs have been made in the treatment of neovascular AMD, effective intervention for atrophic AMD is largely absent. The adequate knowledge of RPE pathology is hindered by a lack of the patients' RPE datasets, especially at the single-cell resolution. In the current study, we delved into a large-scale single-cell resource of AMD donors, in which RPE cells were occupied in a substantial proportion. Bulk RNA-seq datasets of atrophic AMD were integrated to extract molecular characteristics of RPE in the pathogenesis of atrophic AMD. Both in vivo and in vitro models revealed that carboxypeptidase X, M14 family member 2 (CPXM2), was specifically expressed in the RPE cells of atrophic AMD, which might be induced by oxidative stress and involved in the epithelial-mesenchymal transition of RPE cells. Additionally, silencing of CPXM2 inhibited the mesenchymal phenotype of RPE cells in an oxidative stress cell model. Thus, our results demonstrated that CPXM2 played a crucial role in regulating atrophic AMD and might serve as a potential therapeutic target for atrophic AMD.},
}
@article {pmid38807637,
year = {2024},
author = {Li, C and Zhou, L and Sun, H and Yang, MM},
title = {Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis.},
journal = {Clinical interventions in aging},
volume = {19},
number = {},
pages = {939-951},
pmid = {38807637},
issn = {1178-1998},
mesh = {Humans ; *Macular Degeneration/immunology ; *Cellular Senescence ; *Homeostasis ; *Retinal Pigment Epithelium/immunology ; Disease Progression ; Retina/immunology ; },
abstract = {Age-related macular degeneration (AMD) is a degenerative ocular disease primarily affecting central vision in the elderly. Its pathogenesis is complex, involving cellular senescence and immune homeostasis dysregulation. This review investigates the interaction between these two critical biological processes in AMD pathogenesis and their impact on disease progression. Initially, cellular senescence is analyzed, with particular emphasis on retinal damage induced by senescent retinal pigment epithelial cells. Subsequently, the occurrence of immune homeostasis dysregulation within the retina and its mechanistic role in AMD areis explored. Furthermore, the paper also discusses in detail the interplay between cellular senescence and immune responses, forming a vicious cycle that exacerbates retinal damage and may influence treatment outcomes. In summary, a deeper understanding of the interrelation between cellular senescence and immune dysregulation is vital for the developing innovative therapeutic strategies for AMD.},
}
@article {pmid38806699,
year = {2024},
author = {Bourne, RRA and Moledina, M and Azuara-Blanco, A and Saleh, GM and Self, JE and Sivaprasad, S and Sharma, SM and Ross, A and Gilbert, RM and Abdalla Elsayed, MEA and Moon, WY and Doug, M and Mulholland, PJ and Day, AC and Romano, V and Hoad, GV and Kara, M and Murray, A and Gow, L and Ghanchi, F and Patel, PJ and Gale, RP and Dinah, C and Valentine, K and Yelf, C and Poustie, V and , and , },
title = {The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK.},
journal = {Eye (London, England)},
volume = {38},
number = {10},
pages = {1947-1957},
pmid = {38806699},
issn = {1476-5454},
support = {/WT_/Wellcome Trust/United Kingdom ; N/A//Fight for Sight UK/ ; N/A//Macular Society/ ; },
mesh = {Humans ; United Kingdom ; *Ophthalmology/organization &amp; administration ; *Biomedical Research ; Female ; Male ; Middle Aged ; Eye Diseases/therapy/diagnosis ; Surveys and Questionnaires ; Health Priorities ; Adult ; Aged ; },
abstract = {OBJECTIVES: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy.<br><br>METHODS: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents&#xa0;were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them.<br><br>RESULTS: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases).<br><br>CONCLUSIONS: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease.},
}
@article {pmid38806439,
year = {2024},
author = {Luo, P and Zhang, F and Li, X and Wan, J and Bian, W},
title = {Exploring the factors influencing nutritional literacy based on the socioecological model among patients with age-related macular degeneration: a qualitative study from China.},
journal = {BMJ open},
volume = {14},
number = {5},
pages = {e081468},
pmid = {38806439},
issn = {2044-6055},
mesh = {Humans ; China ; Female ; Male ; *Qualitative Research ; Aged ; *Macular Degeneration/rehabilitation/psychology ; *Health Literacy ; *Health Knowledge, Attitudes, Practice ; Middle Aged ; Social Support ; Aged, 80 and over ; Interviews as Topic ; Nutritional Status ; Self Efficacy ; },
abstract = {OBJECTIVES: Although nutritional support is beneficial to the visual rehabilitation of patients with age-related macular degeneration (AMD), a large gap continues to exist between the relevant guidelines and the actual practices of AMD patients; this gap can be attributed to a lack of nutritional literacy. Therefore, this study explored the factors affecting nutritional literacy among AMD patients.<br><br>DESIGN: A qualitative study was carried out based on individual in-person interviews with 15 AMD patients; a semistructured interview guide was used for data collection. The socioecological model (SEM) was employed for data analysis.<br><br>SETTING: The Southwest Hospital in Chongqing Province, China.<br><br>PARTICIPANTS: A purposive sample of 15 AMD patients was recruited between May and June 2023.<br><br>RESULTS: The social ecosystem of patients with AMD has not been positive. At the intrapersonal level, the factors affecting the nutritional literacy of such patients are lack of knowledge, nutrition self-efficacy, economic burdens, dietary preferences and health status. At the interpersonal level, the factors that can influence patients' nutritional literacy are social support and social roles. At the institutional level, the relevant factors are doctor-patient trust and interdisciplinary-team consistency. Finally, at the policy level, a powerful factor is the large gap between policy and implementation.<br><br>DISCUSSION: Nutritional literacy focuses on the changes in an individual's knowledge and behaviour concerning nutrition. To inform the development of nutritional-literacy interventions for people with AMD, medical staff should consider multiple perspectives that can remove the barriers to the SEM at all levels.},
}
@article {pmid38804808,
year = {2024},
author = {Chauhan, K and Narayanan, R},
title = {A novel technique for extensive submacular hemorrhage using high-dose tissue plasminogen activator.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {6},
pages = {921},
doi = {10.4103/IJO.IJO_2295_23},
pmid = {38804808},
issn = {1998-3689},
mesh = {Humans ; Male ; Dose-Response Relationship, Drug ; *Fibrinolytic Agents/administration &amp; dosage ; Fluorescein Angiography ; Fundus Oculi ; *Retinal Hemorrhage/diagnosis/etiology/surgery ; *Tissue Plasminogen Activator/administration &amp; dosage ; Tomography, Optical Coherence ; Visual Acuity ; Vitrectomy/methods ; },
abstract = {BACKGROUND: Submacular hemorrhage (SMH) is a sight-threatening disorder. Choroidal neovascularization secondary to age-related macular degeneration, polypoidal choroidal vasculopathy, trauma, angioid streaks, and pathological myopia are a few important causes. The conventional treatment of massive SMH is vitrectomy with manual removal of the clot with extensive retinectomy with/without tissue plasminogen activator (tPA). The usual dose of subretinal tPA is 10-25 µg.<br><br>PURPOSE: To describe a new surgical approach in a case of massive SMH with retinal detachment without retinectomy.<br><br>SYNOPSIS: In our case of near total hemorrhagic retinal detachment due to subretinal hemorrhage caused by trauma (road traffic accident), the patient presented with a visual acuity of counting fingers. Core vitrectomy was performed and posterior vitreous detachment was induced. The locations for retinotomy to inject and aspirate subretinal blood were selected at the maximum height of retinal elevation near the arcades. Recombinant tPA (10 &#xb5;g/0.1 ml concentration; 0.3 ml injected in two locations) was injected subretinally with a 23-G soft tip cannula in the superotemporal and inferonasal quadrant causing subretinal bleb formation. Subsequently, the surgeon waited for approximately 20 min on the table for the liquefaction of the clot. The liquefied blood and tPA were drained with a silicone soft tip. Endolaser was performed at the retinotomy site and 1000cs silicone oil was injected. No signs of toxicity such as vitritis, vasculitis, or retinal necrosis were noted.<br><br>HIGHLIGHTS: Our unique technique of high-dose intraoperative subretinal tPA (60 &#xb5;g) is safe and helpful in rapid clot lysis and recovery of visual acuity. The patient gained a visual acuity of 20/80 from counting fingers after 1 month of surgery and 20/60 after silicone oil removal. A high dose of tPA aids in the immediate aspiration of blood from a small retinotomy. A 23-G soft tip was used instead of a 41-G subretinal cannula to inject a large quantity of subretinal tPA.<br><br>VIDEO LINK: https://youtu.be/JzZBDUfa3NA.},
}
@article {pmid38802406,
year = {2024},
author = {Mendez, K and Lains, I and Kelly, RS and Gil, J and Silva, R and Miller, J and Vavvas, DG and Kim, I and Miller, J and Liang, L and Lasky-Su, JA and Husain, D},
title = {Metabolomic-derived endotypes of age-related macular degeneration (AMD): a step towards identification of disease subgroups.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {12145},
pmid = {38802406},
issn = {2045-2322},
support = {R01 HL123915/HL/NHLBI NIH HHS/United States ; R01 EY030088/EY/NEI NIH HHS/United States ; RO1EY030088/NH/NIH HHS/United States ; R01HL123915/GF/NIH HHS/United States ; K01 HL146980/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/metabolism/pathology ; *Metabolomics/methods ; Male ; Female ; Aged ; Aged, 80 and over ; Cohort Studies ; Portugal ; Middle Aged ; Metabolome ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a complex pathophysiology and phenotypic diversity. Here, we apply Similarity Network Fusion (SNF) to cluster AMD patients into putative metabolomics-derived endotypes. Using a discovery cohort of 163 AMD patients from Boston, US, and a validation cohort of 214 patients from Coimbra, Portugal, we identified four distinct metabolomics-derived endotypes with varying retinal structural and functional characteristics, confirmed across both cohorts. Patients clustered into Endotype 1 exhibited a milder form of AMD and were characterized by low levels of amino acids in specific metabolic pathways. Meanwhile, patients clustered into both Endotype 3 and 4 were associated with more severe AMD and exhibited low levels of fatty acid metabolites and elevated levels of sphingomyelins and fatty acid metabolites, respectively. These preliminary findings indicate that metabolomics-derived endotyping may offer a refined strategy for categorizing AMD patients based on their specific pathophysiological underpinnings, rather than relying solely on traditional observational clinical indicators.},
}
@article {pmid38801614,
year = {2024},
author = {Brinkmann, M and Viggiano, P and Boscia, G and Müller, T and Castellino, N and Schweighofer, J and Boscia, F and Toro, MD and El-Shabrawi, Y},
title = {Analysis of Choriocapillaris Reperfusion Topography Following Faricimab Treatment for Neovascular Age-Related Macular Degeneration in Therapy-Naïve Patients.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {7},
pages = {1981-1992},
pmid = {38801614},
issn = {2193-8245},
abstract = {INTRODUCTION: To assess changes in choriocapillaris (CC) vascular density surrounding macular neovascularization (MNV) in treatment-naïve age-related macular degeneration (AMD) after faricimab application using optical coherence tomography angiography (OCTA).<br><br>METHODS: Twenty-five eyes of 25 treatment-na&#xef;ve individuals who underwent intravitreal faricimab injections for neovascular AMD (nAMD) with type 1 MNV were included. Spectral-domain optical coherence tomography (SD-OCT) images and en-face swept-source OCTA images were analyzed, and the percentage of CC flow deficit (FD%), FD average area (FDa) and FD number (FDn) in five progressive 20.0-&#x3bc;m-wide concentric rings (R1, R2, R3, R4 and R5) surrounding the dark halo around the MNV were calculated. Image acquisition was carried out prior to the first faricimab injection (T0) and 1 month after the injection (T1).<br><br>RESULTS: The topographical sub-analysis revealed noteworthy changes in all rings at T1 compared to T0. There was a notable progressive reduction in FD% at T1 compared to T0 values across all rings, indicating a gradual CC reperfusion following anti-VEGF treatment. Additionally, the average size of FD decreased after the loading phase. Although not reaching statistical significance, there was a progressive reduction in the FDa across all rings.<br><br>CONCLUSION: Our study highlights a CC FD reduction following the administration of three consecutive faricimab injections. This effect was detected in all rings surrounding the dark halo. These observations suggest a partial CC reperfusion surrounding the MNV, potentially serving as an indicator for disease regression.},
}
@article {pmid38798355,
year = {2024},
author = {Fleming, LL and Defenderfer, M and Demirayak, P and Stewart, P and Decarlo, DK and Visscher, KM},
title = {Impact of deprivation and preferential usage on functional connectivity between early visual cortex and category selective visual regions.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.05.17.593020},
pmid = {38798355},
issn = {2692-8205},
support = {F99 NS113424/NS/NINDS NIH HHS/United States ; },
abstract = {UNLABELLED: Human behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how the removal of input changes brain function. However, an important question has yet to be answered: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details. However, when central vision is lost in conditions like macular degeneration, peripheral vision must be relied upon for those everyday tasks, with certain portions receiving "preferential" usage over others. Using resting-state fMRI collected during total darkness, we examined how deprivation and preferential usage influence the intrinsic functional connectivity of sensory cortex by studying individuals with selective vision loss due to late stages of macular degeneration. We found that cortical regions representing spared portions of the peripheral retina, regardless of whether they are preferentially used, exhibit plasticity of intrinsic functional connectivity in macular degeneration. Cortical representations of spared peripheral retinal locations showed stronger connectivity to MT, a region involved in processing motion. These results suggest that long-term loss of central vision can produce widespread effects throughout spared representations in early visual cortex, regardless of whether those representations are preferentially used. These findings support the idea that connections to visual cortex maintain the capacity for change well after critical periods of visual development.<br><br>HIGHLIGHTS: Portions of early visual cortex representing central vs. peripheral vision exhibit different patterns of connectivity to category-selective visual regions.When central vision is lost, cortical representations of peripheral vision display stronger functional connections to MT than central representations.When central vision is lost, connectivity to regions selective for tasks that involve central vision (FFA and PHA) are not significantly altered.These effects do not depend on which locations of peripheral vision are used more.},
}
@article {pmid38797751,
year = {2024},
author = {Akça, S and Garip, Z and Ekinci, E and Atban, F},
title = {Automated classification of choroidal neovascularization, diabetic macular edema, and drusen from retinal OCT images using vision transformers: a comparative study.},
journal = {Lasers in medical science},
volume = {39},
number = {1},
pages = {140},
pmid = {38797751},
issn = {1435-604X},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Diabetic Retinopathy/diagnostic imaging/classification ; *Choroidal Neovascularization/diagnostic imaging/classification ; *Macular Edema/diagnostic imaging/classification ; *Algorithms ; *Retinal Drusen/diagnostic imaging ; Retina/diagnostic imaging/pathology ; },
abstract = {Classifying retinal diseases is a complex problem because the early problematic areas of retinal disorders are quite small and conservative. In recent years, Transformer architectures have been successfully applied to solve various retinal related health problems. Age-related macular degeneration (AMD) and diabetic macular edema (DME), two prevalent retinal diseases, can cause partial or total blindness. Diseases therefore require an early and accurate detection. In this study, we proposed Vision Transformer (ViT), Tokens-To-Token Vision Transformer (T2T-ViT) and Mobile Vision Transformer (Mobile-ViT) algorithms to detect choroidal neovascularization (CNV), drusen, and diabetic macular edema (DME), and normal using optical coherence tomography (OCT) images. The predictive accuracies of ViT, T2T-ViT and Mobile-ViT achieved on the dataset for the classification of OCT images are 95.14%, 96.07% and 99.17% respectively. Experimental results obtained from ViT approaches showed that Mobile-ViT have superior performance with regard to classification accuracy in comparison with the others. Overall, it has been observed that ViT architectures have the capacity to classify with high accuracy in the diagnosis of retinal diseases.},
}
@article {pmid38797511,
year = {2025},
author = {Iverson, E and Sukhai, M and Quinn, MP and Aubin, MJ and Freeman, EE},
title = {Visual impairment, employment status, and reduction in income: the Canadian Longitudinal Study on Aging.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {60},
number = {1},
pages = {e16-e22},
doi = {10.1016/j.jcjo.2024.04.006},
pmid = {38797511},
issn = {1715-3360},
mesh = {Humans ; Middle Aged ; Male ; Canada/epidemiology ; Female ; *Employment/statistics &amp; numerical data ; *Income/statistics &amp; numerical data ; Prospective Studies ; Visual Acuity/physiology ; *Vision Disorders/epidemiology/economics ; *Aging/physiology ; *Persons with Visual Disabilities/statistics &amp; numerical data ; Follow-Up Studies ; Longitudinal Studies ; Vision, Binocular/physiology ; },
abstract = {OBJECTIVE: To examine the employment status of those with and without visual impairment and eye disease and to examine the association between visual impairment and eye disease and a reduction in income over a 3-year period.<br><br>DESIGN: Population-based prospective cohort study.<br><br>PARTICIPANTS: A total of 12,174 nonretired participants aged 45-64 years old in the Canadian Longitudinal Study on Aging.<br><br>METHODS: Visual impairment was defined if binocular presenting or pinhole-corrected monocular visual acuity in the better eye was worse than 20/40 at baseline. Self-reported diagnoses of age-related macular degeneration (AMD) and glaucoma were collected. Employment status (employed, not employed due to sickness or disability, or unemployed) was based on questions on labour force participation. Income reduction was defined as household income <$50,000 per year at follow-up when household income was &#x2265;$50,000 at baseline. Multinomial and logistic regressions were used to adjust for demographic and health variables.<br><br>RESULTS: Visual impairment using binocular presenting visual acuity (odds ratio [OR]&#x202f;=&#x202f;2.09; 95% CI, 1.21-3.62) and pinhole-corrected visual acuity (OR&#x202f;=&#x202f;2.99; 95% CI, 1.54-5.83) were associated with a higher odds of not being employed due to sickness or disability after adjustment. AMD (OR&#x202f;=&#x202f;1.82; 95% CI, 1.11-3.01) and glaucoma (OR&#x202f;=&#x202f;2.05; 95% CI, 1.28-3.28) at baseline were both associated with reductions in income over a 3-year period after adjustment.<br><br>CONCLUSION: Individuals with visual impairment experienced lower employment, and those with AMD or glaucoma were more likely to have their incomes decline over 3 years. Policies to improve workplace participation by those with vision loss are needed.},
}
@article {pmid38796619,
year = {2024},
author = {Xie, H and Ju, H and Lu, J and Wang, X and Peng, H},
title = {Comparative study on the efficacy of Conbercept and Aflibercept in the treatment of neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11997},
pmid = {38796619},
issn = {2045-2322},
support = {81670881//The National Natural Science Foundation of China financially supported this study/ ; 81670881//The National Natural Science Foundation of China financially supported this study/ ; 81670881//The National Natural Science Foundation of China financially supported this study/ ; 81670881//The National Natural Science Foundation of China financially supported this study/ ; 81670881//The National Natural Science Foundation of China financially supported this study/ ; },
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Male ; Female ; Aged ; Prospective Studies ; Treatment Outcome ; *Visual Acuity/drug effects ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Middle Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; },
abstract = {This study compares the effectiveness of Conbercept and Aflibercept in treating neovascular age-related macular degeneration (nAMD). Conducted at the First Affiliated Hospital of Chongqing Medical University's Ophthalmology Department (May 2020-May 2023), this prospective study enrolled 159 nAMD patients. Participants were randomly divided into two groups: one receiving 0.5 mg Conbercept and the other 2 mg Aflibercept intravitreal injections. Over 12 months, the study, employing a Treat-and-Extend (T&amp;E) regimen, assessed Best-Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT) changes and injection frequency. Of the 159 patients, 137 (149 eyes) completed the study. No significant age difference was found between the groups (P = 0.331). After 12 months, BCVA improved similarly in both groups (Conbercept: 52.8 ± 18.9, Aflibercept: 52.0 ± 19.7 letters; P = 0.820). CRT reduction was also comparable (Conbercept: 246.3 ± 82.8 µm, Aflibercept: 275.9 ± 114.3 µm; P = 0.079). Injection frequencies averaged 6.9 ± 0.7 (Conbercept) and 6.7 ± 0.7 (Aflibercept; P = 0.255). Subtype analysis revealed Type 1 MNV had higher baseline BCVA and lower CRT, with more frequent injections compared to other types. Both Conbercept and Aflibercept are clinically similar in efficacy for nAMD, with the T&amp;E regimen proving therapeutically effective and potentially reducing patient costs. Anti-VEGF treatment efficacy varies across nAMD subtypes, indicating a potential benefit in tailored treatments for specific subtypes.Clinical trial registration number NCT05539235 (Protocol Registration and Results System).},
}
@article {pmid38795692,
year = {2024},
author = {Ren, Y and Liang, H and Xie, M and Zhang, M},
title = {Natural plant medications for the treatment of retinal diseases: The blood-retinal barrier as a clue.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {130},
number = {},
pages = {155568},
doi = {10.1016/j.phymed.2024.155568},
pmid = {38795692},
issn = {1618-095X},
mesh = {*Blood-Retinal Barrier/drug effects ; Humans ; Animals ; *Retinal Diseases/drug therapy ; Diabetic Retinopathy/drug therapy ; Phytotherapy ; Plant Extracts/pharmacology/therapeutic use ; Plants, Medicinal/chemistry ; },
abstract = {BACKGROUND: Retinal diseases significantly contribute to the global burden of visual impairment and blindness. The occurrence of retinal diseases is often accompanied by destruction of the blood‒retinal barrier, a vital physiological structure responsible for maintaining the stability of the retinal microenvironment. However, detailed summaries of the factors damage the blood‒retinal barrier and treatment methods involving natural plant medications are lacking.<br><br>PURPOSE: To comprehensively summarize and analyze the protective effects of active substances in natural plant medications on damage to the blood-retina barrier that occurs when retinal illnesses, particularly diabetic retinopathy, and examine their medicinal value and future development prospects.<br><br>METHODS: In this study, we searched for studies published in the ScienceDirect, PubMed, and Web of Science databases. The keywords used included natural plant medications, plants, natural herbs, blood retinal barrier, retinal diseases, diabetic retinopathy, age-related macular degeneration, and uveitis. Chinese herbal compound articles, non-English articles, warning journals, and duplicates were excluded from the analysis.<br><br>RESULTS: The blood&#x2012;retinal barrier is susceptible to high glucose, aging, immune responses, and other factors that destroy retinal homeostasis, resulting in pathological changes such as apoptosis and increased vascular permeability. Existing studies have shown that the active compounds or extracts of many natural plants have the effect of repairing blood-retinal barrier dysfunction. Notably, berberine, puerarin, and Lycium barbarum polysaccharides exhibited remarkable therapeutic effects. Additionally, curcumin, astragaloside IV, hesperidin, resveratrol, ginsenoside Rb1, luteolin, and Panax notoginseng saponins can effectively protect the blood&#x2012;retinal barrier by interfering with distinct pathways. The active ingredients found in natural plant medications primarily repair the blood&#x2012;retinal barrier by modulating pathological factors such as oxidative stress, inflammation, pyroptosis, and autophagy, thereby alleviating retinal diseases.<br><br>CONCLUSION: This review summarizes a series of plant extracts and plant active compounds that can treat retinal diseases by preventing and treating blood&#x2012;retinal barrier damage and provides reference for the research of new drugs for treating retinal diseases.},
}
@article {pmid38794293,
year = {2024},
author = {Al-Bassam, L and Shearman, GC and Brocchini, S and Alany, RG and Williams, GR},
title = {The Potential of Selenium-Based Therapies for Ocular Oxidative Stress.},
journal = {Pharmaceutics},
volume = {16},
number = {5},
pages = {},
pmid = {38794293},
issn = {1999-4923},
abstract = {Oxidative stress plays a critical role in the development of chronic ocular conditions including cataracts, age-related macular degeneration, and diabetic retinopathy. There is a need to explore the potential of topical antioxidants to slow the progression of those conditions by mediating oxidative stress and maintaining ocular health. Selenium has attracted considerable attention because it is a component of selenoproteins and antioxidant enzymes. The application of selenium to a patient can increase selenoprotein expression, counteracting the effect of reactive oxygen species by increasing the presence of antioxidant enzymes, and thus slowing the progression of chronic ocular disorders. Oxidative stress effects at the biomolecular level for prevalent ocular conditions are described in this review along with some of the known defensive mechanisms, with a focus on selenoproteins. The importance of selenium in the eye is described, along with a discussion of selenium studies and uses. Selenium's antioxidant and anti-inflammatory qualities may prevent or delay eye diseases. Recent breakthroughs in drug delivery methods and nanotechnology for selenium-based ocular medication delivery are enumerated. Different types of selenium may be employed in formulations aimed at managing ocular oxidative stress conditions.},
}
@article {pmid38793219,
year = {2024},
author = {Matsuyama, T and Osaka, N and Yamaguchi, M and Kanamaru, N and Wada, K and Kawakita, A and Murata, K and Sugimoto, K and Okamoto, K},
title = {Evaluation of Phototoxicity of Short-Wavelength Laser Light Utilizing PCNA Accumulation.},
journal = {Micromachines},
volume = {15},
number = {5},
pages = {},
pmid = {38793219},
issn = {2072-666X},
support = {JP20K04521//Japan Society for the Promotion of Science/ ; },
abstract = {In recent years, diseases such as age-related macular degeneration and retinal pigment degeneration caused by excessive exposure to short-wavelength visible light have become significant concerns. With the aim of quantitatively evaluating the toxicity of short-wavelength light, proliferating cell nuclear antigen (PCNA) accumulation at the irradiation site was investigated using live cell imaging techniques to irradiate individual living cells with short-wavelength laser light. By examining the dependency of PCNA accumulation on the irradiation site within the cells and their cell cycle, it was observed that PCNA accumulation occurred only when the cell nucleus of cells in the S phase of the cell cycle was irradiated. We investigated the accumulation of PCNA at the laser irradiation site using laser light at wavelengths of 405 nm and 375 nm, with intensities ranging from 0.5 μW to 9.0 μW. The results confirmed an increase in PCNA accumulation with increasing intensity, and a higher accumulation was observed with laser light irradiation at a wavelength of 375 nm compared to 405 nm. By comparing the PCNA accumulation and 24 h cell viability, we demonstrated the feasibility of quantitatively assessing laser light toxicity through the measurement of PCNA accumulation.},
}
@article {pmid38793125,
year = {2024},
author = {Yordi, S and Cakir, Y and Kalra, G and Cetin, H and Hu, M and Abraham, J and Reese, J and Srivastava, SK and Ehlers, JP},
title = {Ellipsoid Zone Integrity and Visual Function in Dry Age-Related Macular Degeneration.},
journal = {Journal of personalized medicine},
volume = {14},
number = {5},
pages = {},
pmid = {38793125},
issn = {2075-4426},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
abstract = {In this longitudinal retrospective image analysis, conducted on patients diagnosed with dry age-related macular degeneration (AMD) and 5 years of follow-up imaging data, the study aimed to investigate the relationship between ellipsoid zone (EZ) integrity on spectral domain optical coherence tomography (SD-OCT) and visual acuity (VA). Using a machine learning-enabled feature extraction tool, quantitative EZ parameters were derived from SD-OCT images. The analysis revealed significant correlations between EZ integrity metrics and VA. Eyes with excellent VA (≥20/25 Snellen) exhibited higher EZ integrity, including less EZ attenuation, thicker ellipsoid zone-retinal pigment epithelium (EZ-RPE) thickness, and higher EZ intensity, in contrast to eyes with worse VA (≤20/40 Snellen). Additionally, eyes with geographic atrophy (GA) in the foveal region displayed compromised EZ integrity compared to those without GA. Notably, baseline EZ integrity metrics were predictive of future VA loss. These findings suggest that quantitative SD-OCT measurements of EZ integrity could potentially detect early changes in dry AMD and serve as valuable indicators for predicting future functional outcomes. Furthermore, these measurements hold promise for use in clinical trial screenings, offering insights into the progression of the disease and its impact on visual acuity. This study underscores the importance of EZ integrity assessment in understanding and managing dry AMD.},
}
@article {pmid38792993,
year = {2024},
author = {Żuber-Łaskawiec, K and Wilańska, J and Karska-Basta, I and Pociej-Marciak, W and Romanowska-Dixon, B and Sanak, M and Kubicka-Trząska, A},
title = {Circulating Anti-Endothelial Cell Antibodies in Patients with Geographic Atrophy Related to Dry Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {5},
pages = {},
pmid = {38792993},
issn = {1648-9144},
support = {1072.6120.37.2019, dated from 31st January 2019//Jagiellonian Univeristy Medical College/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Geographic Atrophy/blood/immunology ; *Macular Degeneration/blood/complications ; *Autoantibodies/blood ; Middle Aged ; Aged, 80 and over ; Endothelial Cells/immunology ; Retina/immunology ; Case-Control Studies ; },
abstract = {Background and Objectives: Age-related macular degeneration (AMD) is one of the leading causes of central vision loss among elderly patients, and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As inflammation and immune system involvement are strongly suggested to play a central role in promoting the degenerative process and stimulating the onset of complications, we aimed to analyze the frequency of serum anti-retinal (ARAs) and anti-endothelial cell antibodies (AECAs) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably the area of geographic atrophy (GA). Materials and Methods: This study included 41 patients with advanced-stage dry AMD and 50 healthy controls without AMD, matched for gender and age. ARAs were detected by indirect immunofluorescence using monkey retina as an antigen substrate, and the presence of AECAs was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARAs were detected in 36 (87.8%) AMD patients (titers ranged from 1:20 to 1:320) and in 16 (39.0%) (titers ranged from 1:10 to 1:40) controls (p = 0.0000). Twenty of the forty-one patients (48.8%) were positive for AECAs, while in the control group, AECAs were present only in five sera (10.0%). The titers of AECAs in AMD patients ranged from 1:100 to 1:1000, and in the control group, the AECA titers were 1:100 (p = 0.0001). There were no significant correlations between the presence of AECAs and disease activity. Conclusions: This study demonstrates a higher prevalence of circulating AECAs in patients with dry AMD; however, no correlation was found between the serum levels of these autoantibodies and the area of GA.},
}
@article {pmid38792644,
year = {2024},
author = {Winiarczyk, M and Thiede, B and Utheim, TP and Kaarniranta, K and Winiarczyk, D and Michalak, K and Mackiewicz, J},
title = {Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
pmid = {38792644},
issn = {2075-1729},
support = {INFRASTRUKTUR-program (project number: 295910)//The Research Council of Norway/ ; },
abstract = {Neovascular age-related macular degeneration (AMD) is a major cause of irreversible blindness in elderly populations in developed countries. AMD's etiopathology is multifactorial, with strong environmental and genetic components, but the exact molecular pathomechanisms underlying the disease are still unknown. In this study, we analyzed blood serum collected from 74 neovascular AMD patients and 58 healthy controls to identify proteins that may serve as potential biomarkers and expand our knowledge about the etiopathogenesis of the disease. The study revealed 17 differentially expressed proteins-11 up-regulated and 6 down-regulated-in neovascular AMD, which are involved in the biological processes previously linked with the disease-oxidative stress and persistent inflammation, impaired cellular transport, lipid metabolism and blood coagulation. In conclusion, the differences in the expressions of the proteins identified in this study may contribute to our understanding of the mechanisms underlying AMD and possibly serve in future as promising biomarkers.},
}
@article {pmid38792519,
year = {2024},
author = {Ha, JS and Kim, DK and Lee, HS and Jeon, S and Jeon, J and Kim, D and Kim, JS and Kim, B and Kim, M and Cho, KS},
title = {Androgen Deprivation Therapy and Newly Developed Neovascular Age-Related Macular Degeneration Risk in Patients with Prostate Cancer.},
journal = {Journal of clinical medicine},
volume = {13},
number = {10},
pages = {},
pmid = {38792519},
issn = {2077-0383},
support = {2021-KUA-002//The Korean Urological Association/ ; },
abstract = {Background/Objectives: to evaluate the association between androgen deprivation therapy (ADT) and newly developed neovascular age-related macular degeneration (AMD) in patients with prostate cancer. Methods: We identified 228,803 men from the nationwide claims database in the Republic of Korea diagnosed with prostate cancer between 1 August 2009 and 31 December 2018 and followed until April 2021. Cases were defined as those newly diagnosed with neovascular AMD during follow-up. Cases were matched with controls based on age, index date, and follow-up duration, at a case-to-control ratio of 1:4. Adjusted odds ratios (aORs) of incident neovascular AMD associated with ADT were estimated using conditional logistic regression. Results: The main analysis included 1700 cases and 6800 controls, with a median follow-up of 3.42 years. ADT was associated with a reduced risk of incident neovascular AMD in patients with prostate cancer (aOR = 0.840; 95% confidence interval [CI], 0.743-0.951; p = 0.0058) in the multivariable analysis. A cumulative ADT duration less than 1 year was associated with a reduced risk of neovascular AMD (aOR = 0.727; 95% CI, 0.610-0.866; p = 0.0004); however, no association was observed when the duration of ADT was between 1 and 2 years (aOR = 0.862; 95% CI, 0.693-1.074; p = 0.1854) or more than 2 years (aOR = 1.009; 95% CI, 0.830-1.226; p = 0.9304). Conclusions: In patients with prostate cancer, medical castration for less than a year is associated with a reduced risk of incident neovascular AMD. These results suggest that androgens are involved in the pathogenesis of neovascular AMD.},
}
@article {pmid38791541,
year = {2024},
author = {Lee, D and Fu, Z and Hellstrom, A and Smith, LEH},
title = {Therapeutic Effects of Anti-Inflammatory and Anti-Oxidant Nutritional Supplementation in Retinal Ischemic Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {10},
pages = {},
pmid = {38791541},
issn = {1422-0067},
mesh = {Humans ; *Dietary Supplements ; *Antioxidants/therapeutic use/administration &amp; dosage ; *Retinal Diseases/diet therapy/therapy ; *Anti-Inflammatory Agents/therapeutic use/administration &amp; dosage ; Animals ; Ischemia/therapy/diet therapy ; },
abstract = {Appropriate nutrients are essential for cellular function. Dietary components can alter the risk of systemic metabolic diseases, including cardiovascular diseases, cancer, diabetes, and obesity, and can also affect retinal diseases, including age-related macular degeneration, diabetic retinopathy, and glaucoma. Dietary nutrients have been assessed for the prevention or treatment of retinal ischemic diseases and the diseases of aging. In this article, we review clinical and experimental evidence concerning the potential of some nutritional supplements to prevent or treat retinal ischemic diseases and provide further insights into the therapeutic effects of nutritional supplementation on retinopathies. We will review the roles of nutrients in preventing or protecting against retinal ischemic diseases.},
}
@article {pmid38790928,
year = {2024},
author = {Faura, G and Studenovska, H and Sekac, D and Ellederova, Z and Petrovski, G and Eide, L},
title = {The Effects of the Coating and Aging of Biodegradable Polylactic Acid Membranes on In Vitro Primary Human Retinal Pigment Epithelium Cells.},
journal = {Biomedicines},
volume = {12},
number = {5},
pages = {},
pmid = {38790928},
issn = {2227-9059},
support = {TO01000107//Norwegian Research Council/ ; 801133//European Union/ ; No. CZ.02.01.01/00/22_008/0004562//European Regional Development Fund/ ; },
abstract = {Age-related macular degeneration (AMD) is the most frequent cause of blindness in developed countries. The replacement of dysfunctional human retinal pigment epithelium (hRPE) cells by the transplantation of in vitro-cultivated hRPE cells to the affected area emerges as a feasible strategy for regenerative therapy. Synthetic biomimetic membranes arise as powerful hRPE cell carriers, but as biodegradability is a requirement, it also poses a challenge due to its limited durability. hRPE cells exhibit several characteristics that putatively respond to the type of membrane carrier, and they can be used as biomarkers to evaluate and further optimize such membranes. Here, we analyze the pigmentation, transepithelial resistance, genome integrity, and maturation markers of hRPE cells plated on commercial polycarbonate (PC) versus in-house electrospun polylactide-based (PLA) membranes, both enabling separate apical/basolateral compartments. Our results show that PLA is superior to PC-based membranes for the cultivation of hRPEs, and the BEST1/RPE65 maturation markers emerge as the best biomarkers for addressing the quality of hRPE cultivated in vitro. The stability of the cultures was observed to be affected by PLA aging, which is an effect that could be partially palliated by the coating of the PLA membranes.},
}
@article {pmid38790923,
year = {2024},
author = {Wańczura, P and Aebisher, D and Iwański, MA and Myśliwiec, A and Dynarowicz, K and Bartusik-Aebisher, D},
title = {The Essence of Lipoproteins in Cardiovascular Health and Diseases Treated by Photodynamic Therapy.},
journal = {Biomedicines},
volume = {12},
number = {5},
pages = {},
pmid = {38790923},
issn = {2227-9059},
abstract = {Lipids, together with lipoprotein particles, are the cause of atherosclerosis, which is a pathology of the cardiovascular system. In addition, it affects inflammatory processes and affects the vessels and heart. In pharmaceutical answer to this, statins are considered a first-stage treatment method to block cholesterol synthesis. Many times, additional drugs are also used with this method to lower lipid concentrations in order to achieve certain values of low-density lipoprotein (LDL) cholesterol. Recent advances in photodynamic therapy (PDT) as a new cancer treatment have gained the therapy much attention as a minimally invasive and highly selective method. Photodynamic therapy has been proven more effective than chemotherapy, radiotherapy, and immunotherapy alone in numerous studies. Consequently, photodynamic therapy research has expanded in many fields of medicine due to its increased therapeutic effects and reduced side effects. Currently, PDT is the most commonly used therapy for treating age-related macular degeneration, as well as inflammatory diseases, and skin infections. The effectiveness of photodynamic therapy against a number of pathogens has also been demonstrated in various studies. Also, PDT has been used in the treatment of cardiovascular diseases, such as atherosclerosis and hyperplasia of the arterial intima. This review evaluates the effectiveness and usefulness of photodynamic therapy in cardiovascular diseases. According to the analysis, photodynamic therapy is a promising approach for treating cardiovascular diseases and may lead to new clinical trials and management standards. Our review addresses the used therapeutic strategies and also describes new therapeutic strategies to reduce the cardiovascular burden that is induced by lipids.},
}
@article {pmid38790910,
year = {2024},
author = {Cebatoriene, D and Vilkeviciute, A and Gedvilaite, G and Bruzaite, A and Kriauciuniene, L and Zaliuniene, D and Liutkeviciene, R},
title = {CFH (rs1061170, rs1410996), KDR (rs2071559, rs1870377) and KDR and CFH Serum Levels in AMD Development and Treatment Efficacy.},
journal = {Biomedicines},
volume = {12},
number = {5},
pages = {},
pmid = {38790910},
issn = {2227-9059},
support = {P-MIP-23-126//Research Council of Lithuania/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Av-vascular endothelial growth factor (anti-VEGF) therapies have been shown to be effective, but they do not respond optimally to all patients.<br><br>OBJECTIVE: This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the CFH (rs1061170, rs1410996) and KDR (rs2071559, rs1870377) genes and the association of CFH and KDR serum levels in patients with AMD.<br><br>RESULTS: A cohort of 255 patients with early AMD, 252 patients with exudative AMD, and 349 healthy controls underwent genotyping analysis, which revealed significant associations between CFH polymorphisms and the risk of exudative AMD. The CFH rs1061170 CC genotype was associated with an increased risk of early AMD (p = 0.046). For exudative AMD, the CFH rs1061170 TC + CC genotype increased odds (p < 0.001), while the rs1410996 GA + AA genotype decreased odds (p < 0.001). Haplotypes of CFH SNPs were associated with decreased odds of AMD. In terms of response to treatment, none of the SNPs were associated with the response to anti-VEGF treatment. We also found that both early and exudative AMD patients had lower CFH serum levels compared to the control group (p = 0.038 and p = 0.006, respectively). Exudative AMD patients with the CT genotype of CFH rs1061170 had lower CFH serum levels compared to the control group (p = 0.035). Exudative AMD patients with the GG genotype of CFH rs1410996 also had lower CFH serum levels compared to the control group (p = 0.021).<br><br>CONCLUSIONS: CFH polymorphisms influence susceptibility to AMD but do not correlate with a response to anti-VEGF therapy. Further research is imperative to fully evaluate the developmental significance, treatment efficacy, and predictive role in influencing susceptibility to anti-VEGF therapy for KDR and CFH.},
}
@article {pmid38790673,
year = {2024},
author = {Basyal, D and Lee, S and Kim, HJ},
title = {Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {5},
pages = {},
pmid = {38790673},
issn = {2076-3921},
abstract = {Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.},
}
@article {pmid38790643,
year = {2024},
author = {Tsou, SC and Chuang, CJ and Wang, I and Chen, TC and Yeh, JH and Hsu, CL and Hung, YC and Lee, MC and Chang, YY and Lin, HW},
title = {Lemon Peel Water Extract: A Novel Material for Retinal Health, Protecting Retinal Pigment Epithelial Cells against Dynamin-Related Protein 1-Mediated Mitochondrial Fission by Blocking ROS-Stimulated Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {5},
pages = {},
pmid = {38790643},
issn = {2076-3921},
support = {MOST 111-2320-B-040-006-MY3//Ministry of Science and Technology, Taiwan/ ; MOST-112-2320-B-468-002-MY3//Ministry of Science and Technology, Taiwan/ ; },
abstract = {Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of apoptosis and the associated proteins, such as cleaved PARP and cleaved caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.},
}
@article {pmid38790345,
year = {2024},
author = {Muth, DR and Fasler, KF and Kvanta, A and Rejdak, M and Blaser, F and Zweifel, SA},
title = {Real-World Weekly Efficacy Analysis of Faricimab in Patients with Age-Related Macular Degeneration.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {5},
pages = {},
pmid = {38790345},
issn = {2306-5354},
abstract = {Objectives: This study entailed a weekly analysis of real-world data (RWD) on the safety and efficacy of intravitreal (IVT) faricimab in neovascular age-related macular degeneration (nAMD). Methods: A retrospective, single-centre clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich, University of Zurich, Switzerland, approved by the Cantonal Ethics Committee of Zurich, Switzerland. Patients with nAMD were included. Data from patient charts and imaging were analysed. The safety and efficacy of the first faricimab injection were evaluated weekly until 4 weeks after injection. Results: Sixty-three eyes with a complete 4-week follow-up were enrolled. Six eyes were treatment-naïve; fifty-seven eyes were switched to faricimab from another treatment. Neither group showed signs of retinal vasculitis during the 4 weeks after injection. Central subfield thickness (CST) and volume (CSV) showed a statistically significant decrease compared to the baseline in the switched group (CST: p = 0.00383; CSV: p = 0.00702) after 4 weeks. The corrected visual acuity returned to the baseline level in both groups. The macular neovascularization area decreased in both groups, but this was not statistically significant. A complete resolution of sub- and intraretinal fluid after 4 weeks was found in 40% (switched) and 75% (naïve) of the treated patients. Conclusions: The weekly follow-ups reflect the structure-function relationship beginning with a fast functional improvement within two weeks after injection followed by a return to near-baseline levels after week 3. The first faricimab injection in our cohort showed a high safety profile and a statistically significant reduction in macular oedema in switched nAMD patients.},
}
@article {pmid38789988,
year = {2024},
author = {Kozak, A and Ninghetto, M and Wieteska, M and Fiedorowicz, M and Wełniak-Kamińska, M and Kossowski, B and Eysel, UT and Arckens, L and Burnat, K},
title = {Visual training after central retinal loss limits structural white matter degradation: an MRI study.},
journal = {Behavioral and brain functions : BBF},
volume = {20},
number = {1},
pages = {13},
pmid = {38789988},
issn = {1744-9081},
support = {2015/19/B/NZ4/03045//Narodowym Centrum Nauki/ ; },
mesh = {Animals ; *White Matter/diagnostic imaging/pathology ; Cats ; *Magnetic Resonance Imaging/methods ; *Motion Perception/physiology ; Retina/diagnostic imaging/physiopathology ; Male ; Female ; },
abstract = {BACKGROUND: Macular degeneration of the eye is a common cause of blindness and affects 8% of the worldwide human population. In adult cats with bilateral lesions of the central retina, we explored the possibility that motion perception training can limit the associated degradation of the visual system. We evaluated how visual training affects behavioral performance and white matter structure. Recently, we proposed (Kozak et al. in Transl Vis Sci Technol 10:9, 2021) a new motion-acuity test for low vision patients, enabling full visual field functional assessment through simultaneous perception of shape and motion. Here, we integrated this test as the last step of a 10-week motion-perception training.<br><br>RESULTS: Cats were divided into three groups: retinal-lesioned only and two trained groups, retinal-lesioned trained and control trained. The behavioral data revealed that trained cats with retinal lesions were superior in motion tasks, even when the difficulty relied only on acuity. 7&#xa0;T-MRI scanning was done before and after lesioning at 5 different timepoints, followed by Fixel-Based and Fractional Anisotropy Analysis. In cats with retinal lesions, training resulted in a more localized and reduced percentage decrease in Fixel-Based Analysis metrics in the dLGN, caudate nucleus and hippocampus compared to untrained cats. In motion-sensitive area V5/PMLS, the significant decreases in fiber density were equally strong in retinal-lesioned untrained and trained cats, up to 40% in both groups. The only cortical area with Fractional Anisotropy values not affected by central retinal loss was area V5/PMLS. In other visual ROIs, the Fractional Anisotropy values increased over time in the untrained retinal lesioned group, whereas they decreased in the retinal lesioned trained group and remained at a similar level as in trained controls.<br><br>CONCLUSIONS: Overall, our MRI results showed a stabilizing effect of motion training applied soon after central retinal loss induction on white matter structure. We propose that introducing early motion-acuity training for low vision patients, aimed at the intact and active retinal peripheries, may facilitate brain plasticity processes toward better vision.},
}
@article {pmid38789609,
year = {2024},
author = {Hsu, MY and Luo, KS and Chou, CC and Lin, YH and Hung, YC and Chuang, WL and Tsai, SC and Lin, HJ and Yu, TS and Tsai, FJ and Chang, KH},
title = {Association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and macular degeneration in patients with diabetes: a nationwide population-based study in Taiwan.},
journal = {Acta diabetologica},
volume = {61},
number = {9},
pages = {1161-1168},
pmid = {38789609},
issn = {1432-5233},
support = {TTMHH-R1130010//Tungs' Taichung Metro Harbor Hospital research grant/ ; TTMHH-R1130011//Tungs' Taichung Metro Harbor Hospital research grant/ ; MOHW112-TDU-B-212-144004//Ministry of Science and Technology/ ; DMR-111-105//China Medical University Hospital/ ; DMR-112-087//China Medical University Hospital/ ; DMR-113-009//China Medical University Hospital/ ; },
mesh = {Humans ; *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Male ; Taiwan/epidemiology ; Female ; Middle Aged ; *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology ; Aged ; *Macular Degeneration/epidemiology/drug therapy ; Adult ; Retrospective Studies ; Databases, Factual ; },
abstract = {AIMS: Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes.<br><br>METHODS: The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20&#xa0;years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90&#xa0;days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89&#xa0;days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications.<br><br>RESULTS: Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio&#x2009;=&#x2009;0.70, 95%CI&#x2009;=&#x2009;0.66-0.75).<br><br>CONCLUSIONS: We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.},
}
@article {pmid38788546,
year = {2024},
author = {Chen, X and Liu, S and Chen, M and Ni, N and Zhou, R and Wang, Y and Xu, Y and Wang, Y and Gao, H and Zhang, D and Tang, Z and Shu, Q and Zhang, J and Li, L and Ju, Y and Gu, P},
title = {Novel therapeutic perspectives for wet age-related macular degeneration: RGD-modified liposomes loaded with 2-deoxy-D-glucose as a promising nanomedicine.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {175},
number = {},
pages = {116776},
doi = {10.1016/j.biopha.2024.116776},
pmid = {38788546},
issn = {1950-6007},
mesh = {*Liposomes ; *Oligopeptides/chemistry ; Animals ; Humans ; *Nanomedicine/methods ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; *Wet Macular Degeneration/drug therapy/metabolism ; *Deoxyglucose/pharmacology/administration &amp; dosage ; *Vascular Endothelial Growth Factor Receptor-2/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism/drug effects ; Mice ; Mice, Inbred C57BL ; Endothelial Cells/drug effects/metabolism ; },
abstract = {Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.},
}
@article {pmid38788306,
year = {2024},
author = {Zhang, Y and Watson, S and Ramaswamy, Y and Singh, G},
title = {Intravitreal therapeutic nanoparticles for age-related macular degeneration: Design principles, progress and opportunities.},
journal = {Advances in colloid and interface science},
volume = {329},
number = {},
pages = {103200},
doi = {10.1016/j.cis.2024.103200},
pmid = {38788306},
issn = {1873-3727},
mesh = {Humans ; *Macular Degeneration/drug therapy/metabolism ; *Nanoparticles/chemistry ; Intravitreal Injections ; Animals ; Drug Delivery Systems ; Retina/metabolism/drug effects/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. The current standard treatment for AMD involves frequent intravitreal administrations of therapeutic agents. While effective, this approach presents challenges, including patient discomfort, inconvenience, and the risk of adverse complications. Nanoparticle-based intravitreal drug delivery platforms offer a promising solution to overcome these limitations. These platforms are engineered to target the retina specifically and control drug release, which enhances drug retention, improves drug concentration and bioavailability at the retinal site, and reduces the frequency of injections. This review aims to uncover the design principles guiding the development of highly effective nanoparticle-based intravitreal drug delivery platforms for AMD treatment. By gaining a deeper understanding of the physiology of ocular barriers and the physicochemical properties of nanoparticles, we establish a basis for designing intravitreal nanoparticles to optimize drug delivery and drug retention in the retina. Furthermore, we review recent nanoparticle-based intravitreal therapeutic strategies to highlight their potential in improving AMD treatment efficiency. Lastly, we address the challenges and opportunities in this field, providing insights into the future of nanoparticle-based drug delivery to improve therapeutic outcomes for AMD patients.},
}
@article {pmid38788268,
year = {2024},
author = {Vessey, KA and Jobling, AI and Greferath, U and Fletcher, EL},
title = {Pharmaceutical therapies targeting autophagy for the treatment of age-related macular degeneration.},
journal = {Current opinion in pharmacology},
volume = {76},
number = {},
pages = {102463},
doi = {10.1016/j.coph.2024.102463},
pmid = {38788268},
issn = {1471-4973},
mesh = {Humans ; *Autophagy/drug effects ; *Macular Degeneration/drug therapy ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the elderly. Although new therapies have recently emerged, there are currently no ways of preventing the development of the disease. Changes in intracellular recycling processes. Changes in intracellular recycling processes, called autophagy, lead to debris accumulation and cellular dysfunction in AMD models and AMD patients. Drugs that enhance autophagy hold promise as therapies for slowing AMD progression in preclinical models; however, more studies in humans are required. While a definitive cure for AMD will likely hinge on a personalized medicine approach, treatments that enhance autophagy hold promise for slowing vision loss.},
}
@article {pmid38787546,
year = {2024},
author = {Guadron, L and Titchener, SA and Abbott, CJ and Ayton, LN and van Opstal, AJ and Petoe, MA and Goossens, J},
title = {Post-Saccadic Oscillations of the Pupil and Lens Reduce Fixation Stability in Retinitis Pigmentosa and Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {5},
pages = {39},
pmid = {38787546},
issn = {1552-5783},
support = {693400/ERC_/European Research Council/International ; },
mesh = {Humans ; *Saccades/physiology ; *Retinitis Pigmentosa/physiopathology ; Female ; Male ; *Fixation, Ocular/physiology ; Middle Aged ; *Macular Degeneration/physiopathology ; Aged ; *Pupil/physiology ; Lens, Crystalline/physiopathology ; Adult ; Visual Acuity/physiology ; },
abstract = {PURPOSE: Post-saccadic oscillations (PSOs) reflect movements of gaze that result from motion of the pupil and lens relative to the eyeball rather than eyeball rotations. Here, we analyzed the characteristics of PSOs in subjects with age-related macular degeneration (AMD), retinitis pigmentosa (RP), and normal vision (NV). Our aim was to assess the differences in PSOs between people with vision loss and healthy controls because PSOs affect retinal image stability after each saccade.<br><br>METHODS: Participants completed a horizontal saccade task and their gaze was measured using a pupil-based eye tracker. Oscillations occurring in the 80 to 200&#xa0;ms post-saccadic period were described with a damped oscillation model. We compared the amplitude, decay time constant, and frequency of the PSOs for the three different groups. We also examined the correlation between these PSO parameters and the amplitude, peak velocity, and final deceleration of the preceding saccades.<br><br>RESULTS: Subjects with vision loss (AMD, n = 6, and RP, n = 5) had larger oscillation amplitudes, longer decay constants, and lower frequencies than subjects with NV (n = 7). The oscillation amplitudes increased with increases in saccade deceleration in all three groups. The other PSO parameters, however, did not show consistent correlations with either saccade amplitude or peak velocity.<br><br>CONCLUSIONS: Post-saccadic fixation stability in AMD and RP is reduced due to abnormal PSOs. The differences with respect to NV are not due to differences in saccade kinematics, suggesting that anatomic and neuronal variations affect the suspension of the iris and the lens in the patients' eyes.},
}
@article {pmid38786303,
year = {2024},
author = {da Cruz, L and Soomro, T and Georgiadis, O and Nommiste, B and Sagoo, MS and Coffey, P and , },
title = {The Fate of RPE Cells Following hESC-RPE Patch Transplantation in Haemorrhagic Wet AMD: Pigmentation, Extension of Pigmentation, Thickness of Transplant, Assessment for Proliferation and Visual Function-A 5 Year-Follow Up.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
pmid = {38786303},
issn = {2075-4418},
support = {N/A//Pfizer (United Kingdom)/ ; },
abstract = {(1) Background: We reviewed a stem cell-derived therapeutic strategy for advanced neovascular age-related macular degeneration (nAMD) using a human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) monolayer delivered on a coated, synthetic basement membrane (BM)-the patch-and assessed the presence and distribution of hESC-RPE over 5 years following transplantation, as well as functional outcomes. (2) Methods: Two subjects with acute vision loss due to sub-macular haemorrhage in advanced nAMD received the hESC-RPE patch. Systematic immunosuppression was used peri-operatively followed by local depot immunosuppression. The subjects were monitored for five years with observation of RPE patch pigmentation, extension beyond the patch boundary into surrounding retina, thickness of hESC-RPE and synthetic BM and review for migration and proliferation of hESC-RPE. Visual function was also assessed. (3) Results: The two study participants showed clear RPE characteristics of the patch, preservation of some retinal ultrastructure with signs of remodelling, fibrosis and thinning on optical coherence tomography over the 5-year period. For both participants, there was evidence of pigment extension beyond the patch continuing until 12 months post-operatively, which stabilised and was preserved until 5 years post-operatively. Measurement of hESC-RPE and BM thickness over time for both cases were consistent with predefined histological measurements of these two layers. There was no evidence of distant RPE migration or proliferation in either case beyond the monolayer. Sustained visual acuity improvement was apparent for 2 years in both subjects, with one subject maintaining the improvement for 5 years. Both subjects demonstrated initial improvement in fixation and microperimetry compared to baseline, at year 1, although only one maintained this at 4 years post-intervention. (4) Conclusions: hESC-RPE patches show evidence of continued pigmentation, with extension, to cover bare host basement membrane for up to 5 years post-implantation. There is evidence that this represents functional RPE on the patch and at the patch border where host RPE is absent. The measurements for thickness of hESC-RPE and BM suggest persistence of both layers at 5 years. No safety concerns were raised for the hypothetical risk of RPE migration, proliferation or tumour formation. Visual function also showed sustained improvement for 2 years in one subject and 5 years in the other subject.},
}
@article {pmid38786273,
year = {2024},
author = {Miranda, M and Santos-Oliveira, J and Mendonça, AM and Sousa, V and Melo, T and Carneiro, &#xc2;},
title = {Human versus Artificial Intelligence: Validation of a Deep Learning Model for Retinal Layer and Fluid Segmentation in Optical Coherence Tomography Images from Patients with Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {10},
pages = {},
pmid = {38786273},
issn = {2075-4418},
abstract = {Artificial intelligence (AI) models have received considerable attention in recent years for their ability to identify optical coherence tomography (OCT) biomarkers with clinical diagnostic potential and predict disease progression. This study aims to externally validate a deep learning (DL) algorithm by comparing its segmentation of retinal layers and fluid with a gold-standard method for manually adjusting the automatic segmentation of the Heidelberg Spectralis HRA + OCT software Version 6.16.8.0. A total of sixty OCT images of healthy subjects and patients with intermediate and exudative age-related macular degeneration (AMD) were included. A quantitative analysis of the retinal thickness and fluid area was performed, and the discrepancy between these methods was investigated. The results showed a moderate-to-strong correlation between the metrics extracted by both software types, in all the groups, and an overall near-perfect area overlap was observed, except for in the inner segment ellipsoid (ISE) layer. The DL system detected a significant difference in the outer retinal thickness across disease stages and accurately identified fluid in exudative cases. In more diseased eyes, there was significantly more disagreement between these methods. This DL system appears to be a reliable method for accessing important OCT biomarkers in AMD. However, further accuracy testing should be conducted to confirm its validity in real-world settings to ultimately aid ophthalmologists in OCT imaging management and guide timely treatment approaches.},
}
@article {pmid38786253,
year = {2024},
author = {Shechter, Y and Cohen, R and Namestnikov, M and Shapira, A and Barak, A and Barzelay, A and Dvir, T},
title = {Sequential Fabrication of a Three-Layer Retina-like Structure.},
journal = {Gels (Basel, Switzerland)},
volume = {10},
number = {5},
pages = {},
pmid = {38786253},
issn = {2310-2861},
support = {1/CX/CSRD VA/United States ; },
abstract = {Tissue engineering is considered a promising approach to treating advanced degenerative maculopathies such as nonexudative age-related macular degeneration (AMD), the leading cause of blindness worldwide. The retina consists of several hierarchical tissue layers, each of which is supported by a layer underneath. Each of these layers has a different morphology and requires distinct conditions for proper assembly. In fact, a prerequisite step for the assembly of each of these layers is the organization of the layer underneath. Advanced retinal degeneration includes degeneration of the other retina layers, including the choroid, the retinal pigmented epithelium (RPE), and the photoreceptors. Here, we report a step-by-step fabrication process of a three-layer retina-like structure. The process included the 3D printing of a choroid-like structure in an extracellular matrix (ECM) hydrogel, followed by deposition of the RPE monolayer. After the formation of the blood vessel-RPE interface, the photoreceptor cells were deposited to interact with the RPE layer. At the end of the fabrication process, each layer was characterized for its morphology and expression of specific markers, and the integration of the three-layer retina was evaluated. We envision that such a retina-like structure may be able to attenuate the deterioration of a degenerated retina and improve engraftment and regeneration. This retinal implant may potentially be suitable for a spectrum of macular degenerative diseases for which there are currently no cures and may save millions from complete blindness.},
}
@article {pmid38785595,
year = {2024},
author = {Parra-Sanchez, A and Zorrilla-Muñoz, V and Martinez-Navarrete, G and Fernandez, E},
title = {Technological Perception with Rural and Urban Differentiation and Its Influence on the Quality of Life of Older People with Age-Related Macular Degeneration.},
journal = {European journal of investigation in health, psychology and education},
volume = {14},
number = {5},
pages = {1470-1488},
pmid = {38785595},
issn = {2254-9625},
abstract = {The past decade has seen a global increase in population age, especially in developed countries, where aging involves visual diseases such as age-related macular degeneration (AMD), which severely affect quality of life (QoL) and mental health, as well as increase isolation and care costs. This study investigated how persons with AMD perceive the impact of technology use on their QoL, focusing on potential disparities between urban and rural contexts in Spain. Using a cross-sectional observational design, data from the 2020 National Statistics Institute's Disability, Personal Autonomy, and Dependency Situations Survey were analyzed, focusing on QoL aspects based on the WHO items of the WHOQOL-100 scale. The results revealed a generally positive perception of technology among participants, with urban residents perceiving technology's positive impact more favorably. Sex discrepancies in technology perception were also observed, as women exhibited a more positive outlook on technology's influence on QoL. The analysis of QoL aspects, such as 'Visibility', 'Learning', 'Mobility', and 'Domestic life', highlighted distinct challenges faced by rural and urban populations, underscoring the importance of context-specific approaches in technology interventions. However, these perceptions were intertwined with comorbidities, which can exacerbate AMD-related issues. Furthermore, this study explored the role of technology in enhancing QoL among older adults with AMD, examining how it influences daily activities and independence, particularly in the context of AMD management. This study concluded that developing more-inclusive policies tailored to the specific needs of persons with AMD, with special attention to environmental and sex differences, is imperative to enhance the positive impact of technology on their QoL.},
}
@article {pmid38783765,
year = {2024},
author = {Pai, HL and Lin, DP and Chang, HH},
title = {Current updates for hyperuricemia and gout in age-related macular degeneration.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {38},
number = {10},
pages = {e23676},
doi = {10.1096/fj.202400421R},
pmid = {38783765},
issn = {1530-6860},
mesh = {Humans ; *Hyperuricemia/complications/metabolism ; *Macular Degeneration/etiology/metabolism ; *Gout/metabolism/etiology ; Uric Acid/metabolism/blood ; Animals ; },
abstract = {The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro-inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age-related macular degeneration (AMD), a sight-threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro-oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal-induced and non-crystal-induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations.},
}
@article {pmid38782642,
year = {2024},
author = {Mondal, AK and Gaur, M and Advani, J and Swaroop, A},
title = {Epigenome-metabolism nexus in the retina: implications for aging and disease.},
journal = {Trends in genetics : TIG},
volume = {40},
number = {8},
pages = {718-729},
pmid = {38782642},
issn = {0168-9525},
support = {Z01 EY000450/ImNIH/Intramural NIH HHS/United States ; ZIA EY000450/ImNIH/Intramural NIH HHS/United States ; ZIA EY000546/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Aging/genetics/metabolism ; *Epigenome/genetics ; *Retina/metabolism ; *Epigenesis, Genetic ; Macular Degeneration/genetics/metabolism ; Animals ; Gene Expression Regulation/genetics ; Epigenomics ; Glaucoma/genetics/metabolism ; DNA Methylation/genetics ; },
abstract = {Intimate links between epigenome modifications and metabolites allude to a crucial role of cellular metabolism in transcriptional regulation. Retina, being a highly metabolic tissue, adapts by integrating inputs from genetic, epigenetic, and extracellular signals. Precise global epigenomic signatures guide development and homeostasis of the intricate retinal structure and function. Epigenomic and metabolic realignment are hallmarks of aging and highlight a link of the epigenome-metabolism nexus with aging-associated multifactorial traits affecting the retina, including age-related macular degeneration and glaucoma. Here, we focus on emerging principles of epigenomic and metabolic control of retinal gene regulation, with emphasis on their contribution to human disease. In addition, we discuss potential mitigation strategies involving lifestyle changes that target the epigenome-metabolome relationship for maintaining retinal function.},
}
@article {pmid38782152,
year = {2024},
author = {Kazemi, MS and Shoari, A and Salehibakhsh, N and Aliabadi, HAM and Abolhosseini, M and Arab, SS and Ahmadieh, H and Kanavi, MR and Behdani, M},
title = {Anti-angiogenic biomolecules in neovascular age-related macular degeneration; therapeutics and drug delivery systems.},
journal = {International journal of pharmaceutics},
volume = {659},
number = {},
pages = {124258},
doi = {10.1016/j.ijpharm.2024.124258},
pmid = {38782152},
issn = {1873-3476},
mesh = {Humans ; *Drug Delivery Systems/methods ; *Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/administration &amp; dosage ; Animals ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Choroidal Neovascularization/drug therapy ; },
abstract = {Blindness in the elderly is often caused by age-related macular degeneration (AMD). The advanced type of AMD known as neovascular AMD (nAMD) has been linked to being the predominant cause of visual impairment in these people. Multiple neovascular structures including choroidal neovascular (CNV) membranes, fluid exudation, hemorrhages, and subretinal fibrosis, are diagnostic of nAMD. These pathological alterations ultimately lead to anatomical and visual loss. It is known that vascular endothelial growth factor (VEGF), a type of proangiogenic factor, mediates the pathological process underlying nAMD. Therefore, various therapies have evolved to directly target the disease. In this review article, an attempt has been made to discuss general explanations about this disease, all common treatment methods based on anti-VEGF drugs, and the use of drug delivery systems in the treatment of AMD. Initially, the pathophysiology, angiogenesis, and different types of AMD were described. Then we described current treatments and future treatment prospects for AMD and outlined the advantages and disadvantages of each. In this context, we first examined the types of therapeutic biomolecules and anti-VEGF drugs that are used in the treatment of AMD. These biomolecules include aptamers, monoclonal antibodies, small interfering RNAs, microRNAs, peptides, fusion proteins, nanobodies, and other therapeutic biomolecules. Finally, we described drug delivery systems based on liposomes, nanomicelles, nanoemulsions, nanoparticles, cyclodextrin, dendrimers, and composite vehicles that are used in AMD therapy.},
}
@article {pmid38780931,
year = {2024},
author = {Robman, LD and Wolfe, R and Woods, RL and Thao, LTP and Makeyeva, GA and Hodgson, LAB and Lepham, YA and Jachno, K and Phung, J and Maguire, E and Luong, H and Trevaks, RE and Ward, SA and Fitzgerald, SM and Orchard, SG and Lacaze, P and Storey, E and Abhayaratna, WP and Nelson, MR and Guymer, RH and McNeil, JJ},
title = {Effect of Low-Dose Aspirin on the Course of Age-Related Macular Degeneration: A Secondary Analysis of the ASPREE Randomized Clinical Trial.},
journal = {JAMA ophthalmology},
volume = {142},
number = {7},
pages = {627-635},
pmid = {38780931},
issn = {2168-6173},
mesh = {Humans ; *Aspirin/administration &amp; dosage ; Male ; Female ; Aged ; Double-Blind Method ; *Disease Progression ; Aged, 80 and over ; Australia/epidemiology ; Incidence ; Macular Degeneration/prevention &amp; control ; Visual Acuity/physiology ; Follow-Up Studies ; Dose-Response Relationship, Drug ; Platelet Aggregation Inhibitors/administration &amp; dosage/therapeutic use ; Treatment Outcome ; },
abstract = {IMPORTANCE: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in old age. There is no proven intervention to prevent AMD and, apart from lifestyle, nutritional, and supplement advice, there is no intervention to delay its progression.<br><br>OBJECTIVE: To determine the impact of long-term low-dose aspirin on the incidence and progression of AMD.<br><br>The Aspirin in Reducing Events in the Elderly-AMD (ASPREE-AMD) study was an Australian-based substudy of the ASPREE trial, a multicenter, international, randomized, double-masked, placebo-clinical trial investigating the efficacy of low-dose aspirin in prolonging disability-free survival among older individuals. Retinal photography was conducted at baseline from March 2010 to January 2015, then 3 and 5 years after randomization. AMD status was determined using color retinal images and treatment records. Australian participants in ASPREE aged 70 years and older without dementia, independence-limiting physical disability, cardiovascular disease, or chronic illness limiting 5-year survival and with gradable retinal images at baseline were included. Data were analyzed from December 2022 to December 2023.<br><br>INTERVENTIONS: Aspirin (100 mg daily, enteric coated) or placebo.<br><br>MAIN OUTCOMES AND MEASURES: Incidence of AMD and progression from early/intermediate to late AMD. Outcomes were analyzed by modified intention-to-treat analysis.<br><br>RESULTS: A total of 4993 participants were enrolled in this substudy. Baseline characteristics were similar between groups. At the time of sponsor-determined trial termination, retinal follow-up data were available for 3208 participants, 3171 of whom were analyzed for AMD incidence and progression, with a median (IQR) age of 73.5 (71.5-76.4) years and even sex distribution (1619 [51%] female). Median (IQR) follow-up time was 3.1 (3.0-3.5) years. Cumulative AMD incidence was 195 of 1004 (19.4%) in the aspirin group and 187 of 979 (19.1%) in the placebo group (relative risk [RR], 1.02; 95% CI, 0.85-1.22; P&#x2009;=&#x2009;.86). Cumulative progression from early/intermediate AMD to late AMD was observed in 14 of 615 (2.3%) participants in the aspirin group and 18 of 573 (3.1%) in the placebo group (RR, 0.72; 95% CI, 0.36-1.44; P&#x2009;=&#x2009;.36).<br><br>CONCLUSIONS AND RELEVANCE: In this trial, low-dose aspirin administered for 3 years did not affect the incidence of AMD. The evidence was weaker for progression of AMD due to low number of progressed cases. Overall, these results do not support suggestion that low-dose daily aspirin prevents the development or progression of AMD.<br><br>TRIAL REGISTRATION: anzctr.org Identifier: ACTRN12613000755730.},
}
@article {pmid38780873,
year = {2024},
author = {Katipoğlu, Z and Abay, RN},
title = {May the prognostic nutritional index (PNI) play a role in predicting age-related macular degeneration?.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {228},
pmid = {38780873},
issn = {1573-2630},
mesh = {Humans ; Male ; *Macular Degeneration/diagnosis/physiopathology ; Female ; Aged ; *Nutrition Assessment ; Prognosis ; *Nutritional Status ; Aged, 80 and over ; Follow-Up Studies ; Risk Factors ; },
abstract = {AIM: It is known that a healthy and balanced diet plays an important role in the etiopathogenesis of age-related macular degeneration (AMD). The aim of this study is to show the possible relationship between the prognostic nutritional index (PNI) and AMD.<br><br>METHODS: This observational longitudinal study included 50 patients who were diagnosed with AMD and 100 participants as control group in the Ophthalmology Polyclinic of K&#x131;r&#x15f;ehir Ahi Evran Training and Research Hospital between December 2022 and February 2023. The PNI scores of the patients were calculated with the formula (10&#x2009;&#xd7;&#x2009;albumin (g/L)&#x2009;+&#x2009;(0.005&#x2009;&#xd7;&#x2009;total lymphocyte count), using routine hemogram and biochemical assays.<br><br>RESULTS: One hundred fifty participants were included in the study (average age: 73.7&#x2009;&#xb1;&#x2009;8.6&#xa0;years, male: 53.3%). When adjusted for age, sex, and total comorbidity index score via multivariate logistic regression analysis, the association between AMD and PNI scores (OR&#x2009;=&#x2009;0.3; CI: 0.2-0.4; p&#x2009;=&#x2009;0.01) and Charlson Comorbidity Index (CCI) scores (OR&#x2009;=&#x2009;6.8; CI: 2.8-16.6; p&#x2009;=&#x2009;0.01) was statistically significant.<br><br>CONCLUSION: The use of PNI scores may be practical and useful in routine clinical practice for predicting AMD.},
}
@article {pmid38778065,
year = {2024},
author = {Mukai, R and Kataoka, K and Tanaka, K and Miyara, Y and Maruko, I and Nakayama, M and Watanabe, Y and Yamamoto, A and Wakatsuki, Y and Onoe, H and Wakugawa, S and Terao, N and Hasegawa, T and Kawai, M and Maruko, R and Itagaki, K and Honjo, J and Okada, AA and Mori, R and Koizumi, H and Iida, T and Sekiryu, T},
title = {One-year outcomes and safety assessment of faricimab in treatment-naïve patients with neovascular age-related macular degeneration in Japan.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11681},
pmid = {38778065},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; Aged ; Japan ; Retrospective Studies ; Aged, 80 and over ; *Visual Acuity/drug effects ; Treatment Outcome ; Angiogenesis Inhibitors/therapeutic use/adverse effects/administration &amp; dosage ; Macular Degeneration/drug therapy/pathology ; Intravitreal Injections ; Middle Aged ; Tomography, Optical Coherence ; },
abstract = {This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p < 0.01) and central foveal thickness (326 ± 149 [baseline] to 195 ± 82 μm; p < 0.0001) were significant. Dry macula, characterised by the absence of intraretinal or subretinal fluid, was achieved in 65% of cases. Treatment intervals varied, ranging from 8 to 16 weeks, with 44% of eyes extending to a 16-week interval, followed by 33% at 8 weeks, 16% at 12 weeks, 5% at 14 weeks, and 2% at 10 weeks. Notably, 50% of the polypoidal choroidal vasculopathy patients exhibited complete regression of polypoidal lesions between 12 and 15 months. Faricimab treatment in nAMD patients induced significant improvements in central vision and retinal morphology. Two cases of retinal pigment epithelial tears and one case of iritis were reported as ocular complications.},
}
@article {pmid38777835,
year = {2024},
author = {Li, Y and Wei, Y and Ultsch, M and Li, W and Tang, W and Tombling, B and Gao, X and Dimitrova, Y and Gampe, C and Fuhrmann, J and Zhang, Y and Hannoush, RN and Kirchhofer, D},
title = {Cystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4359},
pmid = {38777835},
issn = {2041-1723},
support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; },
mesh = {*High-Temperature Requirement A Serine Peptidase 1/metabolism/genetics ; *Catalytic Domain ; Humans ; *Peptides/chemistry/metabolism/pharmacology ; Peptide Library ; Crystallography, X-Ray ; Protein Binding ; Cystine/chemistry/metabolism ; Models, Molecular ; },
abstract = {Cystine-knot peptides (CKPs) are naturally occurring peptides that exhibit exceptional chemical and proteolytic stability. We leveraged the CKP carboxypeptidase A1 inhibitor as a scaffold to construct phage-displayed CKP libraries and subsequently screened these collections against HTRA1, a trimeric serine protease implicated in age-related macular degeneration and osteoarthritis. The initial hits were optimized by using affinity maturation strategies to yield highly selective and potent picomolar inhibitors of HTRA1. Crystal structures, coupled with biochemical studies, reveal that the CKPs do not interact in a substrate-like manner but bind to a cryptic pocket at the S1' site region of HTRA1 and abolish catalysis by stabilizing a non-competent active site conformation. The opening and closing of this cryptic pocket is controlled by the gatekeeper residue V221, and its movement is facilitated by the absence of a constraining disulfide bond that is typically present in trypsin fold serine proteases, thereby explaining the remarkable selectivity of the CKPs. Our findings reveal an intriguing mechanism for modulating the activity of HTRA1, and highlight the utility of CKP-based phage display platforms in uncovering potent and selective inhibitors against challenging therapeutic targets.},
}
@article {pmid38777310,
year = {2024},
author = {Song, D and Ni, Y and Zhou, Y and Niu, Y and Wang, G and Lv, B and Xie, G and Liu, G},
title = {Evaluation of choroid vascular layer thickness in wet age-related macular degeneration using artificial intelligence.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {47},
number = {},
pages = {104218},
doi = {10.1016/j.pdpdt.2024.104218},
pmid = {38777310},
issn = {1873-1597},
mesh = {Humans ; *Artificial Intelligence ; *Choroid/diagnostic imaging/pathology/blood supply ; Female ; Aged ; Male ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration ; Middle Aged ; Aged, 80 and over ; Case-Control Studies ; },
abstract = {PURPOSE: To facilitate the assessment of choroid vascular layer thickness in patients with wet age-related macular degeneration (AMD) using artificial intelligence (AI).<br><br>METHODS: We included 194 patients with wet AMD and 225 healthy participants. Choroid images were obtained using swept-source optical coherence tomography. The average Sattler layer-choriocapillaris complex thickness (SLCCT), Haller layer thickness (HLT), and choroidal thickness (CT) were auto-measured at 7 regions centered around the foveola using AI and subsequently compared between the 2 groups.<br><br>RESULTS: The SLCCT was lower in the AMD group than in the control group (P < 0.05). The HLT was significantly higher in the AMD group than in the control group at the Tparafovea and T-perifovea in the total population (P < 0.05) and in the &#x2264;70-year subgroup (P < 0.05). The CT was higher in the AMD group than in the control group, particularly at the N-perifovea, T-perifovea, and T-parafovea in the &#x2264;70-year subgroup; Interestingly, it was lower in the AMD group than in the control group at the Nparafovea, N-fovea, foveola, and T-fovea in the >70-year subgroup (P < 0.05).<br><br>CONCLUSION: This novel AI-based auto-measurement was more accurate, efficient, and detailed than manual measurements. SLCCT thinning was observed in wet AMD; however, CT changes depended on the interaction between HLT compensatory thickening and SLCCT thinning.},
}
@article {pmid38777140,
year = {2024},
author = {Patel, NA and Hoyek, S and Al-Khersan, H and Yannuzzi, NA and Smiddy, WE},
title = {A Cost Effectiveness Analysis of Avacincaptad Pegol for the Treatment of Geographic Atrophy with Comparison to Pegcetacoplan.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {11},
pages = {1061-1065},
doi = {10.1016/j.oret.2024.05.011},
pmid = {38777140},
issn = {2468-6530},
mesh = {Humans ; *Geographic Atrophy/drug therapy/economics/diagnosis ; *Cost-Benefit Analysis ; *Intravitreal Injections ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Male ; Female ; Angiogenesis Inhibitors/economics/administration &amp; dosage ; United States ; Cost-Effectiveness Analysis ; },
abstract = {PURPOSE: The purpose of this study was to evaluate the cost effectiveness of the treatment of geographic atrophy (GA) with intravitreal avacincaptad pegol (ACP) and to compare it with pegcetacoplan (PEG).<br><br>DESIGN: Cost analysis based on data from published studies.<br><br>SUBJECTS: None; based on data from published sham control compared with 2 treatment groups in each of the index studies.<br><br>METHODS: Costs were based on 2022 Medicare reimbursement data for both facility (hospital-based) and nonfacility settings in Miami. Specific usage and outcomes were derived from the GATHER2 study as well as DERBY and OAKS trials. For ACP, all patients were treated every month (EM) in year 1 then randomized to every other month (EOM) or EM in year 2. Two-year models were created for patients in the facility setting for extrafoveal (ACP and PEG) and all patients (PEG).<br><br>MAIN OUTCOME MEASURES: Cost, cost utility, and cost per area of GA (in United States dollars).<br><br>RESULTS: The cost to treat GA with ACP in EM and EOM treatment groups over the 2 years as reported was $67 400 and $40 600, respectively. With ACP treatment over 2 years, the daily cost of delaying GA 3.4 months (EM) and 4.5 months (EOM) was $649 (EM) and $356 (EOM). The (facility-based) costs per unit area of retinal pigment epithelium saved for patients with extrafoveal GA over the 2-year period were $119 000/mm[2] (EM ACP) versus $54 000/mm[2] (EM PEG) (P < 0.001), $57 100/mm[2] (EOM ACP) versus $31 400/mm[2] (EOM PEG) (P&#xa0;<&#xa0;0.001), and $45 300/mm[2] (hypothetical EOM from outset ACP).<br><br>CONCLUSION: Treatment of GA with intravitreal ACP EOM was more cost effective than EM. When assessing extrafoveal lesions, ACP was less cost effective than PEG for both EM and EOM treatment.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38776811,
year = {2024},
author = {He, J and Xiong, S and Zhou, W and Qiu, H and Rao, Y and Liu, Y and Shen, G and Zhao, P and Chen, G and Li, J},
title = {Long-term polystyrene nanoparticles exposure reduces electroretinal responses and exacerbates retinal degeneration induced by light exposure.},
journal = {Journal of hazardous materials},
volume = {473},
number = {},
pages = {134586},
doi = {10.1016/j.jhazmat.2024.134586},
pmid = {38776811},
issn = {1873-3336},
mesh = {Animals ; *Polystyrenes/toxicity/chemistry ; *Retinal Degeneration/chemically induced/pathology ; *Nanoparticles/toxicity ; *Mice, Inbred C57BL ; *Oxidative Stress/drug effects ; *Retina/drug effects/radiation effects ; *Retinal Pigment Epithelium/drug effects/pathology/metabolism ; *Light ; Reactive Oxygen Species/metabolism ; Mice ; Electroretinography ; Male ; },
abstract = {The impact of plastic pollution on living organisms have gained significant research attention. However, the effects of nanoplastics (NPs) on retina remain unclear. This study aimed to investigate the effect of long-term polystyrene nanoparticles (PS-NPs) exposure on mouse retina. Eight weeks old C57BL/6 J mice were exposed to PS-NPs at the diameter of 100 nm and concentration of 10 mg/L in drinking water for 3 months. PS-NPs were able to penetrate the blood-retina barrier, accumulated at retinal tissue, caused increased oxidative stress level and reduced scotopic electroretinal responses without remarkable structural damage. PS-NPs exposure caused cytotoxicity and reactive oxygen species accumulation in cultured photoreceptor cell. PS-NPs exposure increased oxidative stress level in retinal pigment epithelial (RPE) cells, leading to changes of gene and protein expression indicative of compromised phagocytic activity and cell junction formation. Long-term PS-NPs exposure also aggravated light-induced photoreceptor cell degeneration and retinal inflammation. The transcriptomic profile of PS-NPs-exposed, light-challenged retinal tissue shared similar features with those of age-related macular degeneration (AMD) patients in the activation of complement-mediated phagocytic and proinflammatory responses. Collectively, these findings demonstrated the oxidative stress- and inflammation-mediated detrimental effect of PS-NPs on retinal function, suggested that long-term PS-NPs exposure could be an environmental risk factor contributing to retinal degeneration.},
}
@article {pmid38776116,
year = {2024},
author = {Farinha, C and Barreto, P and Coimbra, R and Machado, MB and Figueiredo, I and Cachulo, ML and Cunha-Vaz, J and Silva, R},
title = {Age-Related Macular Degeneration and Extramacular Drusen: Genetic Associations in the Coimbra Eye Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {5},
pages = {35},
pmid = {38776116},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; *Macular Degeneration/genetics ; *Retinal Drusen/genetics ; Aged ; Middle Aged ; Aged, 80 and over ; Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide ; Proteins ; },
abstract = {PURPOSE: To explore the association between the genetics of age-related macular degeneration (AMD) and extramacular drusen (EMD) in patients with and without AMD.<br><br>METHODS: We included 1753 eyes (912 subjects) with phenotypic characterization regarding AMD and EMD. Genetic sequencing and the genetic risk score (GRS) for AMD were performed according to the EYE-RISK consortium methodology. To test for differences in the GRS from EMD cases, AMD cases, and controls, a clustered Wilcoxon rank-sum test was used. The association of AMD, EMD, and the GRS was evaluated using logistic regression models adjusted for age and sex. Individual associations of common risk variants for AMD with EMD were explored.<br><br>RESULTS: EMD were found in 755 eyes: 252 (14.4%) with AMD and 503 (28.7%) without. In total, 122 eyes (7.0%) had only AMD, and 876 (50.0%) were controls. EMD were strongly associated with AMD (odds ratio [OR], 3.333; 95% confidence interval [CI], 2.356-4.623; P < 0.001). The GRS was associated with an increased risk of AMD (OR, 1.416; 95% CI, 1.218-1.646; P < 0.001) but not with EMD. Individually, the common risk variants ARMS2 rs10490924 (P = 0.042), C3 rs2230199 (P = 0.042), and CETP rs5817082 (P = 0.042) were associated with EMD, after adjustment for AMD, sex, and age.<br><br>CONCLUSIONS: We found a strong association between EMD and AMD, suggesting a common pathogenesis. The GRS for AMD was not associated with EMD, but a partially overlapping genetic basis was suggested when assessing individual risk variants. We propose that EMD per se do not represent an increase in the global genetic risk for AMD.},
}
@article {pmid38775688,
year = {2024},
author = {Dieckmann, BW and Paguaga, ME and McCollum, GW and Penn, JS and Uddin, MI},
title = {Role of NLRP3 Inflammasomes in Monocyte and Microglial Recruitments in Choroidal Neovascularization.},
journal = {ImmunoHorizons},
volume = {8},
number = {5},
pages = {363-370},
pmid = {38775688},
issn = {2573-7732},
support = {P30 EY008126/EY/NEI NIH HHS/United States ; R01 EY023397/EY/NEI NIH HHS/United States ; R01 EY029693/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Choroidal Neovascularization/metabolism/pathology ; Mice ; *Inflammasomes/metabolism ; *Interleukin-1beta/metabolism ; *Indenes ; *Microglia/metabolism ; *Monocytes/metabolism ; Mice, Knockout ; Sulfones/pharmacology ; Mice, Inbred C57BL ; Furans/pharmacology ; Receptors, CCR2/metabolism/genetics ; Macrophages/metabolism/immunology ; Sulfonamides/pharmacology ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Carrier Proteins/metabolism/genetics ; Choroid/metabolism/pathology ; Disease Models, Animal ; Lasers/adverse effects ; Macular Degeneration/pathology/metabolism/genetics ; },
abstract = {Although the pathogenesis of choroidal neovascularization (CNV) is largely unknown in age-related macular degeneration (AMD), inflammasomes may contribute to CNV development and progression. To understand the role NLRP3 inflammasomes in CNV, we used Ccr2RFPCx3cr1GFP dual-reporter mice and immunostaining techniques to confirm localization of NLRP3 inflammasomes in the laser-induced CNV (LCNV) lesions. Confocal microscopy was used to image and quantify LCNV volumes. MCC950 was used as NLRP3 inhibitor. ELISA and quantitative RT-PCR were used to confirm the activation of NLRP3 by monitoring the expression of IL-1β protein and mRNA in choroidal tissues from LCNV mice. In addition, NLRP3 (-/-) LCNV mice were used to investigate whether NLRP3 inflammasomes contribute to the development of LCNV lesions. We observed that red fluorescent protein (RFP)-positive monocyte-derived macrophages and GFP-positive microglia-derived macrophages, in addition to other cell types, were localized in LCNV lesions at day 7 post-laser injury. In addition, NLRP3 inflammasomes are associated with LCNV lesions. Inhibition of NLRP3 inflammasomes, using MCC950, caused an increased Ccr2RFP-positive macrophages, Cx3cr1GFP-positive microglia, and other cells, resulting in an increase in total lesion size. NLRP3 (-/-) LCNV mice showed significantly increased lesion size compared with age-matched controls. Inhibition of NLRP3 resulted in decreased IL-1β mRNA and protein expression in the choroidal tissues, suggesting that increased lesion size may not be directly related to IL-1β.},
}
@article {pmid38773500,
year = {2024},
author = {Barzelay, A and Daniels, A and Cohen, GY and Barak, A and Schwartz, S and Katz, G},
title = {Pneumatic displacement with intravitreal tPA injection versus vitrectomy with sub retinal tPA injection in small and medium sub macular hemorrhages- a multicenter comparative study.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {218},
pmid = {38773500},
issn = {1471-2415},
mesh = {Humans ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Vitrectomy/methods ; *Retinal Hemorrhage/therapy/diagnosis/drug therapy ; Retrospective Studies ; Male ; Female ; *Visual Acuity ; *Intravitreal Injections ; Aged ; *Tomography, Optical Coherence ; *Fibrinolytic Agents/administration &amp; dosage ; Middle Aged ; Aged, 80 and over ; },
abstract = {PURPOSE: Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue plasminogen activator (tPA) injection procedure, and pneumatic displacement of submacular hemorrhage with intravitreal tPA injection.<br><br>METHODS: A retrospective chart review of patients with sub macular hemorrhage (SMH) was performed. Data was collected from 150 patients with sub macular hemorrhage. Patients were followed up from the day of admission and up to a year post surgery. Evaluation included visual acuity, optical coherence tomography (OCT), fundus examination and rates of complications.<br><br>RESULTS: Pars plana vitrectomy procedure has showed a better visual outcome in small SMH. Comparing complications between the two treatment modalities, no significant difference has been found in the study.<br><br>CONCLUSIONS: Pars plana vitrectomy and tPA showed a clear advantage with a trend of better visual acuity as well as a significant predictor to better visual acuity for small and medium sub macular hemorrhage.},
}
@article {pmid38772676,
year = {2024},
author = {Park, AS and Thompson, B},
title = {Non-invasive brain stimulation and vision rehabilitation: a clinical perspective.},
journal = {Clinical &amp; experimental optometry},
volume = {107},
number = {6},
pages = {594-602},
doi = {10.1080/08164622.2024.2349565},
pmid = {38772676},
issn = {1444-0938},
mesh = {Humans ; *Vision Disorders/rehabilitation/physiopathology/etiology ; Transcranial Magnetic Stimulation/methods ; Transcranial Direct Current Stimulation/methods ; Visual Acuity/physiology ; },
abstract = {Non-invasive brain stimulation techniques allow targeted modulation of brain regions and have emerged as a promising tool for vision rehabilitation. This review presents an overview of studies that have examined the use of non-invasive brain stimulation techniques for improving vision and visual functions. A description of the proposed neural mechanisms that underpin non-invasive brain stimulation effects is also provided. The clinical implications of non-invasive brain stimulation in vision rehabilitation are examined, including their safety, effectiveness, and potential applications in specific conditions such as amblyopia, post-stroke hemianopia, and central vision loss associated with age-related macular degeneration. Additionally, the future directions of research in this field are considered, including the need for larger and more rigorous clinical trials to validate the efficacy of these techniques. Overall, this review highlights the potential for brain stimulation techniques as a promising avenue for improving visual function in individuals with impaired vision and underscores the importance of continued research in this field.},
}
@article {pmid38771461,
year = {2024},
author = {Abraldes, MJ and Calvo, P and Gámez Lechuga, M and Merino, M and Martín Lorenzo, T and Maravilla-Herrera, P and Gil Jiménez, B and Ruiz-Moreno, JM},
title = {Burden of Disease Study of Patients with Neovascular Age-Related Macular Degeneration in Spain.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {7},
pages = {1925-1935},
pmid = {38771461},
issn = {2193-8245},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that causes severe and irreversible vision loss. The disease can therefore have a significant impact on the life of patients' and their families. The aim of this study was to evaluate the socio-economic burden of nAMD in Spain.<br><br>METHODS: The annual cost per patient with nAMD was estimated for the first, second, and third year (or beyond) of treatment since diagnosis. Several cost categories were considered including direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labor productivity losses (LPL), and intangible costs (IC) related to loss of quality of life. The average annual cost per patient was estimated by assigning a unit price or financial proxy to the resources consumed per patient. Reference year of costs was 2021.<br><br>RESULTS: The mean annual cost of nAMD was estimated at &#x20ac;17,265, &#x20ac;15,403, and &#x20ac;14,465 per patient in the first, second, and third year of treatment after diagnosis. There was an additional one-off cost of &#x20ac;744 associated with the diagnosis of nAMD. DHC accounted for most of the total annual cost per patient independent of the year of treatment since diagnosis (48% in year&#xa0;1; 42% in year&#xa0;2; 39% in year&#xa0;3). Similarly, DNHC had an important contribution to the total costs (32% in year&#xa0;1; 35% in year&#xa0;2; 37% in year&#xa0;3), followed by IC (20% in year&#xa0;1; 23% in year&#xa0;2; 24% in year&#xa0;3), while the contribution of patients' LPL was minimal.<br><br>CONCLUSION: This study estimated a high economic burden associated with nAMD for patients and their families, the healthcare system, and society at large. There is a need to improve the management of these patients to reduce the impact of nAMD disease progression.},
}
@article {pmid38770073,
year = {2024},
author = {Ramakrishnan, MS and Kovach, JL and Wykoff, CC and Berrocal, AM and Modi, YS},
title = {American Society of Retina Specialists Clinical Practice Guidelines on Multimodal Imaging for Retinal Disease.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {3},
pages = {234-246},
pmid = {38770073},
issn = {2474-1272},
abstract = {Purpose: Advancements in retinal imaging have augmented our understanding of the pathology and structure-function relationships of retinal disease. No single diagnostic test is sufficient; rather, diagnostic and management strategies increasingly involve the synthesis of multiple imaging modalities. Methods: This literature review and editorial offer practical clinical guidelines for how the retina specialist can use multimodal imaging to manage retinal conditions. Results: Various imaging modalities offer information on different aspects of retinal structure and function. For example, optical coherence tomography (OCT) and B-scan ultrasonography can provide insights into the microstructural anatomy; fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT angiography (OCTA) can reveal vascular integrity and perfusion status; and near-infrared reflectance and fundus autofluorescence (FAF) can characterize molecular components within tissues. Managing retinal vascular diseases often includes fundus photography, OCT, OCTA, and FA to evaluate for macular edema, retinal ischemia, and the secondary complications of neovascularization (NV). OCT and FAF play a key role in diagnosing and treating maculopathies. FA, OCTA, and ICGA can help identify macular NV, posterior uveitis, and choroidal venous insufficiency, which guides treatment strategies. Finally, OCT and B-scan ultrasonography can help with preoperative planning and prognostication in vitreoretinal surgical conditions. Conclusions: Today, the retina specialist has access to numerous retinal imaging modalities that can augment the clinical examination to help diagnose and manage retinal conditions. Understanding the capabilities and limitations of each modality is critical to maximizing its clinical utility.},
}
@article {pmid38768851,
year = {2024},
author = {Merino, P and Cerdán Llach, I and Gago Argüello, A and Gómez de Liaño, P and Yáñez-Merino, J},
title = {Characteristics and type of strabismus associated to macular diplopia. Treatment outcomes.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {99},
number = {7},
pages = {275-280},
doi = {10.1016/j.oftale.2024.05.003},
pmid = {38768851},
issn = {2173-5794},
mesh = {Humans ; Female ; Male ; Retrospective Studies ; *Strabismus/etiology ; Aged ; *Diplopia/etiology ; Middle Aged ; Treatment Outcome ; Aged, 80 and over ; Adult ; Macula Lutea ; Retinal Diseases/complications ; Amblyopia/etiology/therapy ; },
abstract = {OBJECTIVE: To study the clinical characteristics of macular diplopia, treatment, and outcome.<br><br>METHODS: Retrospective descriptive study of cases referred to the ocular motility section of a tertiary hospital with diplopia, diagnosed with macular diplopia between 2022-23. The etiology of the macular pathology and the type of associated strabismus were recorded. The result was considered good if the diplopia improved or was eliminated with the medical or surgical treatment. Follow-up time from the onset of diplopia until data collection was recorded.<br><br>RESULTS: a total of 19 cases comprised the sample (63.2% women), mean age: 67.16 years. Amblyopia (21.1%), high myopia (47.4%), epirretinal membrane (ERM) (36.8%), neovascular membrane (26.3%), macular hole (10.5%), and lamellar (15.8%), and age macular degeneration (5.3%) were registered. The 47.4% had vertical diplopia, horizontal: 5.3 and 47.4% mixed. The mean horizontal deviation was: 7.3 PD (prism diopters) and vertical: 6.22 PD. Ocular extorsion was observed in 26.3%, and intorsion: 5.3%. Torticollis was present in 15.8%. The treatment consisted of strabismus surgery&#xa0;+&#xa0;Botox (15.8%), strabismus surgery (47.4%), medical treatment with Fresnel prims or Scotch cellophane (36.8%). A 68.4% presented a good result at the end of the study. The mean follow-up was 55.58 months.<br><br>CONCLUSIONS: Misregistration of macular photoreceptors is the most common cause of binocular diplopia in patients with ERM or other macular pathologies. Most complains of vertical or mixed diplopia. Sensorimotor evaluation of these patients should be thorough. Early diagnosis prevents unnecessary prescription of prism glasses. Surgical and/or medical treatment achieves good results in most cases.},
}
@article {pmid38768294,
year = {2024},
author = {Liu, K and Li, Y and Zhong, X and Hou, Y and Fei, S and Chen, E and Tan, M},
title = {Protection effect of lutein-loaded Pickering emulsion prepared via ultrasound-assisted Maillard reaction conjugates on dry age-related macular degeneration.},
journal = {Food &amp; function},
volume = {15},
number = {12},
pages = {6347-6358},
doi = {10.1039/d4fo00673a},
pmid = {38768294},
issn = {2042-650X},
mesh = {Animals ; *Emulsions/chemistry ; *Lutein/pharmacology/chemistry/administration &amp; dosage ; *Maillard Reaction ; Mice ; *Macular Degeneration ; Male ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a prominent cause of vision loss among the elderly, and the treatment options for dry AMD (dAMD) are severely limited. Lutein has a favorable effect on the treatment of dAMD. Algae oil, rich in docosahexaenoic acid (DHA), is considered an effective intervention for eye diseases. In this study, casein-mannose conjugates were prepared to form algal oil-in-water Pickering emulsions by ultrasound-assisted Maillard reaction. As the ultrasound time increased from 0 to 25 min, the droplet size decreased to 648.2 ± 21.18 nm, which substantially improved the stability of the Pickering emulsions. The retention of lutein in the Pickering emulsions under ultrasonic treatment for 20 min was significantly improved under different conditions. The simulated gastrointestinal digestion revealed that ultrasound-assisted Pickering emulsions are an effective method for improving the bioaccessibility of lutein (19.76%-53.34%). In vivo studies elucidated that the lutein-loaded Pickering emulsions could effectively alleviate retinal thinning induced by sodium iodate (NaIO3) in mice with dAMD. Mechanistically, lutein-loaded Pickering emulsions significantly reduced oxidative stress by decreasing the MDA level, increasing the SOD production, and reducing the retinal ROS production. These findings explored the protective effects of lutein-loaded Pickering emulsions on dAMD and offered promising prospects for the nutritional intervention of dAMD.},
}
@article {pmid38767357,
year = {2024},
author = {Paterson, CA and Weatherston, D and Teeples, T and Vargis, E},
title = {Isolation of Primary Porcine Retinal Pigment Epithelial Cells for In Vitro Modeling.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {207},
pages = {},
doi = {10.3791/66079},
pmid = {38767357},
issn = {1940-087X},
mesh = {*Retinal Pigment Epithelium/cytology ; Animals ; Swine ; Cytological Techniques/methods ; Epithelial Cells/cytology ; },
abstract = {The retinal pigment epithelium (RPE) is a crucial monolayer in the outer retina responsible for supporting photoreceptors. RPE degeneration commonly occurs in diseases marked by progressive vision loss, such as age-related macular degeneration (AMD). Research on AMD often relies on human donor eyes or induced pluripotent stem cells (iPSCs) to represent the RPE. However, these RPE sources require extended differentiation periods and substantial expertise for culturing. Additionally, some research institutions, particularly those in rural areas, lack easy access to donor eyes. While a commercially available immortalized RPE cell line (ARPE-19) exists, it lacks essential in vivo RPE features and is not widely accepted in many ophthalmology research publications. There is a pressing need to obtain representative primary RPE cells from a more readily available and cost-effective source. This protocol elucidates the isolation and subculture of primary RPE cells obtained post-mortem from porcine eyes, which can be sourced locally from commercial or academic suppliers. This protocol necessitates common materials typically found in tissue culture labs. The result is a primary, differentiated, and cost-effective alternative to iPSCs, human donor eyes, and ARPE-19 cells.},
}
@article {pmid38766158,
year = {2024},
author = {Koirala, A and Marshak-Rothstein, A and Ksander, BR and Gregory-Ksander, M},
title = {Fas Ligand enhances vessel maturation and inhibits vascular leakage associated with age-related macular degeneration.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {38766158},
issn = {2693-5015},
support = {P30 EY003790/EY/NEI NIH HHS/United States ; R01 AR055634/AR/NIAMS NIH HHS/United States ; R21 EY022433/EY/NEI NIH HHS/United States ; },
abstract = {Neovascular age-related macular degeneration (AMD), results from choroidal neovascularization (CNV), retinal edema and loss of photoreceptors. Previous studies suggested that Fas Ligand (FasL) on retinal pigment epithelial cells inhibited CNV by inducing apoptosis of infiltrating Fas+ vascular endothelial cells. However, induction of apoptosis depends on membrane-bound (mFasL) while the FasL cleavage product (sFasL) is neuroprotective. To better understand how FasL regulates the development of CNV, we used a mouse model of laser CNV to evaluate the development of CNV in mice with a FasL cleavage site mutation (ΔCS) and can only express the membrane-bound form of FasL. There was no significant difference in CNV size and area of vascular leakage in homozygous FasL[ΔCS/ΔCS] mice when compared to wild type mice. Unexpectedly, heterozygous FasL[ΔCS/WT] mice developed significantly less vascular leakage and showed accelerated neovessel maturation. However, CNV was not prevented in heterozygous FasL[ΔCS/WT] mice if the Fas receptor was deleted in myeloid cells (FasL[ΔCS/+] Fas[flox/flox] Cre[LysM]). Thus, FasL-mediated CNV inhibition depends on the extent of FasL cleavage, and on FasL engagement of Fas+ myeloid cells. Moreover, accelerated neovessel maturation prevents vascular leakage in AMD.},
}
@article {pmid38765984,
year = {2024},
author = {Chen, Y and Vats, A and Xi, Y and Wolf-Johnston, A and Clinger, O and Arbuckle, R and Dermond, C and Li, J and Stolze, D and Sahel, JA and Jackson, E and Birder, L},
title = {Oral 8-aminoguanine against age-related retinal degeneration.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {38765984},
issn = {2693-5015},
support = {R01 AG056944/AG/NIA NIH HHS/United States ; R01 EY033049/EY/NEI NIH HHS/United States ; S10 RR019003/RR/NCRR NIH HHS/United States ; R01 CA256068/CA/NCI NIH HHS/United States ; R01 DK135076/DK/NIDDK NIH HHS/United States ; R01 EY030991/EY/NEI NIH HHS/United States ; R01 HL109002/HL/NHLBI NIH HHS/United States ; P30 EY008098/EY/NEI NIH HHS/United States ; },
abstract = {Visual decline in the elderly is often attributed to retinal aging, which predisposes the tissue to pathologies such as age-related macular degeneration. Currently, effective oral pharmacological interventions for retinal degeneration are limited. We present a novel oral intervention, 8-aminoguanine (8-AG), targeting age-related retinal degeneration, utilizing the aged Fischer 344 rat model. A low-dose 8-AG regimen (5 mg/kg body weight) via drinking water, beginning at 22 months for 8 weeks, demonstrated significant retinal preservation. This was evidenced by increased retinal thickness, improved photoreceptor integrity, and enhanced electroretinogram responses. 8-AG effectively reduced apoptosis, oxidative damage, and microglial/macrophage activation associated with aging retinae. Age-induced alterations in the retinal purine metabolome, characterized by elevated levels of inosine, hypoxanthine, and xanthine, were partially mitigated by 8-AG. Transcriptomics highlighted 8-AG's anti-inflammatory effects on innate and adaptive immune responses. Extended treatment to 17 weeks further amplified the retinal protective effects. Moreover, 8-AG showed temporary protective effects in the Rho [P23H/+] mouse model of retinitis pigmentosa, reducing active microglia/macrophages. Our study positions 8-AG as a promising oral agent against retinal aging. Coupled with previous findings in diverse disease models, 8-AG emerges as a promising anti-aging compound with the capability to reverse common aging hallmarks.},
}
@article {pmid38765280,
year = {2024},
author = {Kim, BS and Choi, RY and Kweon, H and Lee, JH and Kim, IW and Seo, M},
title = {Oxya chinensis sinuosa (OC) Extracts Protects ARPE-19 Cells against Oxidative Stress via Activation of the Mitogen-Activated Protein Kinases (MAPKs)/ Nuclear Factor-κB (NF-κB) Pathway.},
journal = {Food science of animal resources},
volume = {44},
number = {3},
pages = {699-709},
pmid = {38765280},
issn = {2636-0780},
abstract = {Oxya chinensis sinuosa (OC) is a well-known edible insect. Several researches on the health benefits of OC consumption have been performed to date; however, their effect on eye health remains largely unknown. This study aimed to assess the protective effects of OC extracts on the oxidative stress on the retinal pigment epithelium (RPE) cells. Oxidative damage has been identified as one of the key regulatory factors in age-related macular degeneration. H2O2-induced reactive oxygen species (ROS) production, a well-known oxidative stress factor, can cause cell death in retinal pigment epithelia cells. In this study, we found that three OC extracts effectively prevented H2O2-induced ROS production and subsequent death of ARPE-19 cells in a dose-dependent manner. In addition, the OC extracts inhibited the phosphorylation of mitogen-activated protein kinases including p38, JNK, and ERK. The OC extracts restored IκBα degradation induced by H2O2, indicating that OC extracts suppressed the activation of nuclear factor-κB. Furthermore, the three OC extracts were shown to have antioxidant effects by up-regulating the intracellular expression of key antioxidant proteins such as SOD, NQO, and HO-1. Here we demonstrated the antioxidant and anti-apoptotic effects of the OC extracts on ARPE-19, indicating their potential role in improving eye health. These results suggest that three OC extracts plays a critical role in oxidative stress-induced cell death protects in ARPE-19 cells.},
}
@article {pmid38763919,
year = {2024},
author = {Perus, M and Courtaut, F and Pais de Barros, JP and Aires, V and Hermetet, F and Delmas, D},
title = {VEGF-R2/CAV-1 Interaction Induced by Resveratrol/Eicosapentaenoic Acid/Docosahexaenoic Acid-Enriched Formulation through Functional Detergent-Resistant Membranes Is Associated with Decreased VEGF-A Release in ARPE-19 Cells.},
journal = {Molecular nutrition &amp; food research},
volume = {68},
number = {11},
pages = {e2300893},
doi = {10.1002/mnfr.202300893},
pmid = {38763919},
issn = {1613-4133},
support = {//French Government/ ; //FEDER (European Funding for Regional Economic Development)/ ; //THEA Laboratories/ ; },
mesh = {Humans ; *Docosahexaenoic Acids/pharmacology ; *Eicosapentaenoic Acid/pharmacology ; *Vascular Endothelial Growth Factor A/metabolism ; *Resveratrol/pharmacology ; *Retinal Pigment Epithelium/drug effects/metabolism ; *Caveolin 1/metabolism ; *Vascular Endothelial Growth Factor Receptor-2/metabolism ; Cell Line ; Macular Degeneration/metabolism/drug therapy ; },
abstract = {SCOPE: Omega-3 fatty acids (O3FAs) and resveratrol (RSV) are known to be beneficial for certain eye diseases, such as age-related macular degeneration (AMD). Neovascular AMD is characterized by abnormal blood vessel formation due to the excessive synthesis of vascular endothelial growth factor (VEGF) by retinal pigment epithelium (RPE) cells. The study investigates whether a formulation based on eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and RSV is capable of counteracting VEGF-A secretion, and elucidates the molecular mechanism.<br><br>METHODS AND RESULTS: The study finds, using ELISA, that O3FAs/RSV reduces VEGF-A secretion in human RPE cells. This phenomenon is related to the increased interaction between VEGF-receptor 2 (VEGF-R2) and caveolin-1 (CAV-1), a protein of detergent-resistant membranes (DRMs), as determined by co-immunoprecipitation and proximity ligation assay. Using microscale thermophoresis, the study confirms that O3FAs/RSV causes a high-affinity interaction. Isolation and analysis of DRMs reveal that this interaction is concomitant with VEGF-R2 relocalization in DRMs. The depletion of DRMs by a cholesterol-chelating agent blocks the VEGF-R2/CAV-1 interaction and EPA/DHA/RSV-mediated impairment of VEGF production.<br><br>CONCLUSION: This specific interaction can provide a new strategy for countering VEGF-A production in human RPE cells and, consequently, reducing neovascularization in AMD. Further preclinical studies involving O3FAs and polyphenols are warranted.},
}
@article {pmid38762243,
year = {2024},
author = {Ponzini, E},
title = {Tear biomarkers.},
journal = {Advances in clinical chemistry},
volume = {120},
number = {},
pages = {69-115},
doi = {10.1016/bs.acc.2024.03.002},
pmid = {38762243},
issn = {2162-9471},
mesh = {Humans ; *Tears/metabolism/chemistry ; *Biomarkers/analysis/metabolism ; Eye Diseases/diagnosis/metabolism ; },
abstract = {An extensive exploration of lacrimal fluid molecular biomarkers in understanding and diagnosing a spectrum of ocular and systemic diseases is presented. The chapter provides an overview of lacrimal fluid composition, elucidating the roles of proteins, lipids, metabolites, and nucleic acids within the tear film. Pooled versus single-tear analysis is discussed to underline the benefits and challenges associated with both approaches, offering insights into optimal strategies for tear sample analysis. Subsequently, an in-depth analysis of tear collection methods is presented, with a focus on Schirmer's test strips and microcapillary tubes methods. Alternative tear collection techniques are also explored, shedding light on their applicability and advantages. Variability factors, including age, sex, and diurnal fluctuations, are examined in the context of their impact on tear biomarker analysis. The main body of the chapter is dedicated to discussing specific biomarkers associated with ocular discomfort and a wide array of ocular diseases. From dry eye disease and thyroid-associated ophthalmopathy to keratoconus, age-related macular degeneration, diabetic retinopathy, and glaucoma, the intricate relationship between molecular biomarkers and these conditions is thoroughly dissected. Expanding beyond ocular pathologies, the chapter explores the applicability of tear biomarkers in diagnosing systemic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and cancer. This broader perspective underscores the potential of lacrimal fluid analysis in offering non-invasive diagnostic tools for conditions with far-reaching implications.},
}
@article {pmid38761206,
year = {2024},
author = {Woo, KM and Mahrous, MA and D'Amico, DJ and Kiss, S and Kovacs, KD},
title = {Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3493-3499},
pmid = {38761206},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Tomography, Optical Coherence/methods ; Middle Aged ; *HIV Infections/drug therapy/complications ; Prevalence ; *Receptors, Purinergic P2X7/metabolism ; Aged ; Purinergic P2X Receptor Antagonists ; Fluorescein Angiography/methods ; Macular Degeneration/diagnosis/drug therapy ; Follow-Up Studies ; Fundus Oculi ; Lamivudine/therapeutic use ; Visual Acuity ; Dideoxynucleosides/therapeutic use ; Macula Lutea/pathology/diagnostic imaging ; Cyclopropanes ; Dideoxyadenosine/analogs &amp; derivatives ; },
abstract = {PURPOSE: P2X7 receptor (P2X7R) is a purinergic cation channel whose activation has been linked with age-related macular degeneration (ARMD). Several nucleoside reverse transcriptase inhibitors, zidovudine (AZT), lamivudine (3TC) and abacavir (ABC), have been shown to inhibit P2X7R and improve outcomes in animal models of ARMD. Our aim is to investigate the association between chronic AZT, 3TC, and ABC therapy and ARMD in a clinical setting.<br><br>METHODS: This is a retrospective cohort study comparing 445 patients with HIV and confirmed usage of AZT, 3TC, and ABC against 200 patients with HIV without usage of AZT, 3TC, and ABC and 445 non-HIV infected patients. Fundus examination and spectral domain optical coherence tomography (SD-ODT) were used to measure prevalence of early-intermediate stage ARMD, geographic atrophy, and exudative ARMD.<br><br>RESULTS: There was no statistically significant difference in the prevalence of early-intermediate stage ARMD between the HIV infected patients with a history of AZT, 3TC, and ABC use and the HIV infected patients without AZT, 3TC, and ABC use (p&#x2009;=&#x2009;0.887). There was also no statistically significant difference in the prevalence of geographical atrophy (p&#x2009;=&#x2009;0.062) and exudative AMD (p&#x2009;>&#x2009;0.999) between the HIV infected patients with a history of AZT, 3TC, and ABC use and non-HIV infected patients.<br><br>CONCLUSION: We did not find an effect of P2X7R inhibiting antiretrovirals usage on early-intermediate stage ARMD, geographical atrophy, or exudative ARMD. Studies with larger cohort and more rigorous medication history are needed to assess the effects on geographical atrophy or exudative ARMD.},
}
@article {pmid38761033,
year = {2024},
author = {Sendecki, A and Ledwoń, D and Nycz, J and Wąsowska, A and Boguszewska-Chachulska, A and Mitas, AW and Wylęgała, E and Teper, S},
title = {A deep learning approach to explore the association of age-related macular degeneration polygenic risk score with retinal optical coherence tomography: A preliminary study.},
journal = {Acta ophthalmologica},
volume = {102},
number = {7},
pages = {e1029-e1039},
doi = {10.1111/aos.16710},
pmid = {38761033},
issn = {1755-3768},
support = {07/010/BKM23/1027 (BKM-522/RIB1/2023)//Silesian University of Technology/ ; STRATEGMED1/234261/2/NCBR/2014//Narodowe Centrum Bada&#x144; i Rozwoju/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Deep Learning ; Male ; Female ; Aged ; *Macular Degeneration/genetics/diagnosis ; Risk Factors ; Genome-Wide Association Study/methods ; Retina/diagnostic imaging/pathology ; Middle Aged ; Risk Assessment/methods ; Genetic Risk Score ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a complex eye disorder affecting millions worldwide. This article uses deep learning techniques to investigate the relationship between AMD, genetics and optical coherence tomography (OCT) scans.<br><br>METHODS: The cohort consisted of 332 patients, of which 235 were diagnosed with AMD and 97 were controls with no signs of AMD. The genome-wide association studies summary statistics utilized to establish the polygenic risk score (PRS) in relation to AMD were derived from the GERA European study. A PRS estimation based on OCT volumes for both eyes was performed using a proprietary convolutional neural network (CNN) model supported by machine learning models. The method's performance was assessed using numerical evaluation metrics, and the Grad-CAM technique was used to evaluate the results by visualizing the features learned by the model.<br><br>RESULTS: The best results were obtained with the CNN and the Extra Tree regressor (MAE&#x2009;=&#x2009;0.55, MSE&#x2009;=&#x2009;0.49, RMSE&#x2009;=&#x2009;0.70, R[2]&#x2009;=&#x2009;0.34). Extending the feature vector with additional information on AMD diagnosis, age and smoking history improved the results slightly, with mainly AMD diagnosis used by the model (MAE&#x2009;=&#x2009;0.54, MSE&#x2009;=&#x2009;0.44, RMSE&#x2009;=&#x2009;0.66, R[2]&#x2009;=&#x2009;0.42). Grad-CAM heatmap evaluation showed that the model decisions rely on retinal morphology factors relevant to AMD diagnosis.<br><br>CONCLUSION: The developed method allows an efficient PRS estimation from OCT images. A new technique for analysing the association of OCT images with PRS of AMD, using a deep learning approach, may provide an opportunity to discover new associations between genotype-based AMD risk and retinal morphology.},
}
@article {pmid38760766,
year = {2024},
author = {Zhang, M and Liu, X and Gong, Y and Qian, T and Zhou, H and Wang, Y and Wu, J and Sun, X and Yu, S},
title = {Double-dose investigation of aflibercept in neovascular age-related macular degeneration (DIANA): a real-world study.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {215},
pmid = {38760766},
issn = {1471-2415},
support = {22YF1435500//Shanghai Sailing Program/ ; 82171076//National Natural Science Foundation of China/ ; SHDC2020CR2040B//Shanghai Municipal Hospital Development Center/ ; },
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Male ; Female ; Retrospective Studies ; *Intravitreal Injections ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Tomography, Optical Coherence/methods ; Aged, 80 and over ; Dose-Response Relationship, Drug ; Follow-Up Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND: To investigate the clinical effects of double-dose (4 mg) aflibercept treatment in neovascular age-related macular degeneration (nAMD), compared with the standard-dose (2 mg) treatment.<br><br>METHODS: A total of 108 eyes from 97 patients with nAMD and received intravitreal aflibercept 2&#xa0;mg and/or 4&#xa0;mg treatment were retrospectively reviewed. The changes of central macular thickness (CMT)/ pigmental epithelium detachment height and the recurrence rate of exudation during the 12-month follow-up were compared between the 2&#xa0;mg group and the 4&#xa0;mg group. Self-control comparisons (2&#xa0;mg switch to 4&#xa0;mg) were also made between two regimens.<br><br>RESULTS: Compared with the 2&#xa0;mg group, tendencies of lower intraretinal fluid incidence and more CMT reduction were observed in the 4&#xa0;mg group. The later one was also observed when eyes switching from 2&#xa0;mg to 4&#xa0;mg regimen. The median remission interval was 5 months in the 4&#xa0;mg group, 2 months longer than the 3 months in the 2&#xa0;mg group (P&#x2009;=&#x2009;0.452). Injections needed in the 4&#xa0;mg group were 3.644&#x2009;&#xb1;&#x2009;1.670, less than the 4.286&#x2009;&#xb1;&#x2009;2.334 injections in the 2&#xa0;mg group within 12 months as well (P&#x2009;=&#x2009;0.151). However, no associated vision benefits were gained from the double-douse regimen. No markedly increased-intraocular pressure events, or other adverse events were found in two groups.<br><br>CONCLUSIONS: Compared to the aflibercept 2&#xa0;mg treatment in nAMD, tendencies of anatomic gains and relieving treatment burden were brought by the aflibercept 4&#xa0;mg treatment. This study may have additional importance, given the further application of high-dose aflibercept in real-world settings.},
}
@article {pmid38760463,
year = {2024},
author = {Amer, R and Koriat, A},
title = {Aqueous humor perturbations in chronic smokers: a proteomic study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11279},
pmid = {38760463},
issn = {2045-2322},
mesh = {Humans ; *Aqueous Humor/metabolism ; *Proteomics/methods ; Male ; Female ; Middle Aged ; Smoking/adverse effects ; Proteome/metabolism ; Biomarkers/metabolism ; Smokers ; Aged ; Adult ; },
abstract = {The detrimental effects of smoking are multisystemic and its effects on the eye health are significant. Smoking is a strong risk factor for age-related nuclear cataract, age-related macular degeneration, glaucoma, delayed corneal epithelial healing and increased risk of cystoid macular edema in patients with intermediate uveitis among others. We aimed to characterize the aqueous humor (AH) proteome in chronic smokers to gain insight into its perturbations and to identify potential biomarkers for smoking-associated ocular pathologies. Compared to the control group, chronic smokers displayed 67 (37 upregulated, 30 downregulated) differentially expressed proteins (DEPs). Analysis of DEPs from the biological point of view revealed that they were proteins involved in complement activation, lymphocyte mediated immunity, innate immune response, cellular oxidant detoxification, bicarbonate transport and platelet degranulation. From the molecular function point of view, DEPs were involved in oxygen binding, oxygen carrier activity, hemoglobin binding, peptidase/endopeptidase/cysteine-type endopeptidase inhibitory activity. Several of the upregulated proteins were acute phase reactant proteins such as clusterin, alpha-2-HS-glycoprotein, fibrinogen, alpha-1-antitrypsin, C4b-binding protein and serum amyloid A-2. Further research should confirm if these proteins might serve as biomarkers or therapeutic target for smoking-associated ocular diseases.},
}
@article {pmid38760453,
year = {2024},
author = {Kwon, HY and Kim, J and Ahn, SJ},
title = {Screening practices and risk assessment for maculopathy in pentosan polysulfate users across different exposure levels.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11270},
pmid = {38760453},
issn = {2045-2322},
support = {NRF-2021R1G1A1013360//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Pentosan Sulfuric Polyester/adverse effects ; Male ; Female ; Middle Aged ; *Macular Degeneration/epidemiology/chemically induced/diagnosis ; Risk Assessment ; Aged ; Adult ; Incidence ; Republic of Korea/epidemiology ; Mass Screening/methods ; Cohort Studies ; },
abstract = {In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate (PPS) users and assessed the relationship between these outcomes and drug exposure levels. Using a health claims database that covers approximately 50 million Koreans, we identified 138,593 individuals who were prescribed PPS between 2010 and 2021. For the 133,762 PPS users who initiated therapy between 2012 and 2021, the cumulative PPS dose for each participant was evaluated, and based on their cumulative PPS dose, patients were categorized into the high-risk (≥ 500 g), low-risk (50-500 g), and minimal exposure (< 50 g) groups. We analyzed the performance and methods of these examination methods used between 2018 and 2021 and compared them among cumulative dose groups to determine whether high-risk users underwent maculopathy screening more frequently or appropriately. We assessed the cumulative incidence of overall macular degeneration and maculopathy excluding common macular diseases following PPS therapy initiation. Most PPS users (99.7%) received a cumulative PPS dose < 500 g and the high- and low-risk groups comprised 445 (0.3%) and 22,185 (16.6%) patients, respectively. During the study period, monitoring examinations were conducted in 52.6% and 49.4% of high- and low-risk patients, respectively, revealing no significant difference between the two groups (P = 0.156). No significant differences were observed in the annual percentages of patients receiving ophthalmic examinations between the high- and low-risk groups (all P > 0.05). The cumulative incidences of overall macular degeneration and maculopathy excluding common macular diseases in high-risk users were 19.3% and 9.0%, respectively, which were significantly different from those of low-risk users (both P < 0.001). Multivariate Cox regression analysis revealed significantly higher risks of maculopathy excluding common macular diseases in the low- (Hazard ratio [HR] of 1.55 [95% CI 1.13-2.12]) and high-risk groups (HR of 1.66 [95% CI 1.22-2.27]) compared to the minimal exposure group. Our findings suggest a need for increased emphasis on PPS maculopathy screening in high-risk patients, highlighting raising awareness regarding exposure-dependent risks and the establishment of screening guidelines.},
}
@article {pmid38759795,
year = {2024},
author = {Woo, SJ and Jung, JA and Kim, T and Oh, I and Kim, MY and Bressler, NM},
title = {Association of baseline factors with 1-year outcomes in the SB11-ranibizumab equivalence trial: A post hoc analysis.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {3},
pages = {100069},
doi = {10.1016/j.apjo.2024.100069},
pmid = {38759795},
issn = {2162-0989},
mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage ; Male ; Female ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use ; *Intravitreal Injections ; Prospective Studies ; Aged ; Middle Aged ; Biosimilar Pharmaceuticals/therapeutic use ; Wet Macular Degeneration/drug therapy/physiopathology ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Double-Blind Method ; Aged, 80 and over ; },
abstract = {PURPOSE: To identify baseline factors associated with 1-year outcomes when treating neovascular age-related macular degeneration (nAMD) with ranibizumab biosimilar SB11 or reference ranibizumab (rRBZ), and to compare efficacy of the two products within subgroups judged to be clinically relevant.<br><br>DESIGN: Post hoc analysis of a prospective, equivalence phase 3 randomized clinical trial (RCT) METHODS: 705 patients with nAMD were randomized 1:1 to receive SB11 or rRBZ for 48 weeks. Pooled and randomized groups were used to identify baseline factors associated with clinical outcomes at Week 52 using multiple linear regression models. Significant factors identified in regression analyses were confirmed in analyses of variance. Subgroup analyses comparing best-corrected visual acuity (BCVA) changes between SB11 and rRBZ were conducted.<br><br>RESULTS: 634 (89.9%) participants completed the 52-week visit. Regression analyses showed that younger age, lower BCVA, and smaller total lesion area at baseline were associated with greater BCVA gain at Week 52, while older age, lower BCVA, and thicker central subfield thickness (CST) at baseline were predictors of greater CST reduction in the pooled group. Subgroup analyses demonstrated that BCVA outcomes appeared comparable for the SB11 and rRBZ groups.<br><br>CONCLUSION: Post hoc analyses of the SB11-rRBZ equivalence study showed that baseline age, BCVA, CST, and total lesion area were prognostic factors for visual or anatomical outcomes of nAMD, while subgroup analyses demonstrated comparable results for SB11 and rRBZ. Collectively, the results appear comparable to similar RCTs of anti-vascular endothelial growth factor reference products for nAMD and strengthen confidence in the biosimilarity of SB11.},
}
@article {pmid38758638,
year = {2024},
author = {Kunala, K and Tang, JAH and Bowles Johnson, KE and Huynh, KT and Parkins, K and Kim, HJ and Yang, Q and Sparrow, JR and Hunter, JJ},
title = {Near Infrared Autofluorescence Lifetime Imaging of Human Retinal Pigment Epithelium Using Adaptive Optics Scanning Light Ophthalmoscopy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {5},
pages = {27},
pmid = {38758638},
issn = {1552-5783},
support = {P30 EY001319/EY/NEI NIH HHS/United States ; R01 EY012951/EY/NEI NIH HHS/United States ; R01 EY032116/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/diagnostic imaging/metabolism ; *Ophthalmoscopy/methods ; Adult ; Middle Aged ; Animals ; Female ; Mice ; Male ; Young Adult ; *Optical Imaging/methods ; Reproducibility of Results ; Infrared Rays ; ATP-Binding Cassette Transporters/genetics/metabolism ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities.<br><br>METHODS: NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8&#xa0;weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO.<br><br>RESULTS: The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8&#xb0; and 12&#xb0;) was longer compared to near-foveal regions (0&#xb0; and 2&#xb0;). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [&#x3c4;m], 0.75 [&#x3c4;1], 0.65 [&#x3c4;2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse.<br><br>CONCLUSIONS: NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.},
}
@article {pmid38758378,
year = {2024},
author = {Ota, H and Kataoka, K and Asai, K and Takeuchi, J and Nakano, Y and Nakamura, K and Todoroki, T and Nishiguchi, KM},
title = {Five-year outcomes of treat and extend regimen using intravitreal aflibercept injection for treatment-naïve age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3483-3491},
pmid = {38758378},
issn = {1435-702X},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Intravitreal Injections ; Retrospective Studies ; *Visual Acuity ; Male ; Female ; Follow-Up Studies ; *Tomography, Optical Coherence ; Aged ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Time Factors ; *Fluorescein Angiography ; Aged, 80 and over ; Fundus Oculi ; Angiogenesis Inhibitors/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Macula Lutea/pathology ; Middle Aged ; },
abstract = {PURPOSE: This study evaluated the long-term outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with aflibercept according to a treat-and-extend (T&amp;E) regimen for up to 5 years. Methods This retrospective study included 112 eyes of 111 patients with nAMD who received aflibercept according to the T&amp;E regimen. The patients received 3 monthly injections of aflibercept followed by a T&amp;E regimen for at least 12 months. Data, including best-corrected visual acuity (BCVA), treatment interval, presence of exudation, central retinal thickness, and central choroidal thickness were analyzed.<br><br>RESULTS: Of the 112 consecutive eyes, 66 completed the 5-year follow-up. After 5 years of treatment, BCVA (logMAR) was significantly better than baseline (0.29 &#xb1; 0.31 at baseline and 0.18 &#xb1; 0.23 at 5 years, P < 0.01). A mean of 7.0 &#xb1; 1.5 injections in the first year and 4.9 &#xb1; 2.2 injections per year thereafter were required. In eyes with subretinal hyperreflective material (SHRM) at baseline, BCVA at baseline and 5 years were significantly worse than in eyes without SHRM at baseline and 5 years. However, the eyes with SHRM required fewer injections and exhibited greater BCVA improvement.<br><br>CONCLUSION: This retrospective study demonstrated the effectiveness of the T&amp;E regimen with aflibercept in managing nAMD over a 5-year period, maintaining significant improvements in BCVA.},
}
@article {pmid38757252,
year = {2024},
author = {Chang, FY and Huang, CH and Yang, CH and Chang, JT and Yang, CM and Ho, TC and Hsieh, YT and Lai, TT and Lin, CW and Lin, CP and Chen, YC and Lai, YJ and Chen, PL and Hsu, JS and Chen, TC},
title = {Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {6},
pages = {655-664},
doi = {10.1111/ceo.14388},
pmid = {38757252},
issn = {1442-9071},
support = {109-004734//National Taiwan University Hospital, Taipei, Taiwan/ ; },
mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/genetics ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Aged ; *Visual Acuity/physiology ; *Polymorphism, Single Nucleotide ; *Wet Macular Degeneration/drug therapy/genetics/diagnosis/physiopathology ; *Genome-Wide Association Study ; Ranibizumab/administration &amp; dosage ; Tomography, Optical Coherence ; Genotype ; Follow-Up Studies ; Fluorescein Angiography ; Treatment Outcome ; Aged, 80 and over ; Bevacizumab/administration &amp; dosage/therapeutic use ; Middle Aged ; Genetic Predisposition to Disease ; High-Temperature Requirement A Serine Peptidase 1 ; },
abstract = {BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response.<br><br>METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed.<br><br>RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P&#x2009;=&#x2009;0.005), SRF (P&#x2009;=&#x2009;0.044), and fibrovascular PED (P&#x2009;=&#x2009;0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P&#x2009;=&#x2009;0.046) and serous PED (P&#x2009;=&#x2009;0.049).<br><br>CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.},
}
@article {pmid38755404,
year = {2024},
author = {Akula, M and McNamee, SM and Love, Z and Nasraty, N and Chan, NPM and Whalen, M and Avola, MO and Olivares, AM and Leehy, BD and Jelcick, AS and Singh, P and Upadhyay, AK and Chen, DF and Haider, NB},
title = {Retinoic acid related orphan receptor α is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD.},
journal = {Gene therapy},
volume = {31},
number = {7-8},
pages = {413-421},
pmid = {38755404},
issn = {1476-5462},
support = {P30 EY003790/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; ATP-Binding Cassette Transporters/genetics/metabolism ; Dependovirus/genetics ; *Disease Models, Animal ; *Genetic Therapy/methods ; Geographic Atrophy/genetics/metabolism/therapy ; Macular Degeneration/genetics/metabolism/therapy ; *Mice, Knockout ; *Nuclear Receptor Subfamily 1, Group F, Member 1/genetics/metabolism ; *Retinal Degeneration/genetics/therapy/metabolism ; *Stargardt Disease/genetics ; },
abstract = {Degeneration of the macula is associated with several overlapping diseases including age-related macular degeneration (AMD) and Stargardt Disease (STGD). Mutations in ATP Binding Cassette Subfamily A Member 4 (ABCA4) are associated with late-onset dry AMD and early-onset STGD. Additionally, both forms of macular degeneration exhibit deposition of subretinal material and photoreceptor degeneration. Retinoic acid related orphan receptor α (RORA) regulates the AMD inflammation pathway that includes ABCA4, CD59, C3 and C5. In this translational study, we examined the efficacy of RORA at attenuating retinal degeneration and improving the inflammatory response in Abca4 knockout (Abca4[-/-]) mice. AAV5-hRORA-treated mice showed reduced deposits, restored CD59 expression and attenuated amyloid precursor protein (APP) expression compared with untreated eyes. This molecular rescue correlated with statistically significant improvement in photoreceptor function. This is the first study evaluating the impact of RORA modifier gene therapy on rescuing retinal degeneration. Our studies demonstrate efficacy of RORA in improving STGD and dry AMD-like disease.},
}
@article {pmid38755107,
year = {2024},
author = {Kim, J and Yoon, S and Kim, HYS},
title = {Prevalence of Selected Ophthalmic Diseases Using a Smartphone-Based Fundus Imaging System in Quang Tri and Thai Nguyen, Vietnam.},
journal = {Healthcare informatics research},
volume = {30},
number = {2},
pages = {162-167},
pmid = {38755107},
issn = {2093-3681},
abstract = {OBJECTIVES: This study investigated the prevalence of ophthalmic diseases in Quang Tri and Thai Nguyen, Vietnam, utilizing a smartphone-based fundus imaging (SBFI) system.<br><br>METHODS: This cross-sectional study included nearly 10,000 patients who visited community health centers between July and August 2019. All participants underwent visual acuity testing and fundus imaging. We collected demographic data and medical histories, and fundus images were captured using the EYELIKE system. Data were compiled on an online platform, allowing clinicians from other regions to make diagnoses.<br><br>RESULTS: The study revealed significant variations in visual acuity and the prevalence of ophthalmic diseases between the two regions. Quang Tri had a higher proportion of individuals with good eyesight compared to Thai Nguyen. In Quang Tri, nearly 50% of the population had media haze, while in Thai Nguyen, about one-third of the population was affected. The prevalence of glaucomatous optic nerve and age-related macular degeneration was approximately 1% higher in Quang Tri than in Thai Nguyen. These findings provide valuable insights into the eye health status of these regions, indicating that eye health in Quang Tri was poorer than in Thai Nguyen.<br><br>CONCLUSIONS: The prevalence rates of ophthalmic conditions in this study were within the expected ranges compared to those in other Asian countries, though they were somewhat low. The SBFI method, being simpler and more efficient than the Rapid Assessment of Avoidable Blindness, offers a promising approach for measuring and estimating the prevalence of ophthalmic diseases.},
}
@article {pmid38754401,
year = {2024},
author = {Roshanshad, A and Moosavi, SA and Arevalo, JF},
title = {Association of the Complement Factor H Y402H Polymorphism and Response to Anti-Vascular Endothelial Growth Factor Treatment in Age-Related Macular Degeneration: An Updated Meta-Analysis.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {358-386},
doi = {10.1159/000539377},
pmid = {38754401},
issn = {1423-0259},
mesh = {Humans ; *Complement Factor H/genetics ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/genetics ; *Angiogenesis Inhibitors/therapeutic use ; *Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/drug therapy ; Genotype ; },
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to several causes, including genetic factors. We evaluated the effects of Complement Factor H (CFH) rs1061170/Y402H polymorphism on the response to anti-VEGF therapy among AMD patients.<br><br>METHODS: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were used for a literature search. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated to assess the effects of CFH Y402H polymorphism on the response to anti-VEGF therapy in AMD. I2 was used to present the amount of heterogeneity. We used STATA version 14.0 software.<br><br>RESULTS: Twenty-five papers reporting data for 4,681 patients were included in this study. Better response to anti-VEGF therapy was seen in T over C (OR = 1.25, 95% CI = 1.04-1.50), TT over CC (OR = 1.60, 95% CI = 1.06-2.4), and TT + TC over CC (OR = 1.68, 95% CI = 1.23-2.28) genotypes. There was no significant difference in the three other genetic models (TT vs. TC, TT vs. TC + CC, TC vs. TT + CC). In Asians, no significant difference was observed in all six genetic models. Ranibizumab and bevacizumab had similar efficacy; however, conbercept was more effective in homozygous genotypes. The literature indicated that TT and TC genotypes and T allele were associated with a better functional response, while the CC genotype and C alleles had a better anatomical response. The combination of risk alleles in ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents.<br><br>CONCLUSION: In patients with AMD, the CFH Y402H is a predictor of the response to anti-VEGF agents and should be considered in the treatment plan.},
}
@article {pmid38753023,
year = {2024},
author = {Che Azemin, MZ and Mohd Tamrin, MI and Yusof, F and Salam, A},
title = {The impact of image resolution on diagnostic accuracy using fractal dimension in identifying diabetic retinopathy, glaucoma, and age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {10},
pages = {3409-3411},
pmid = {38753023},
issn = {1435-702X},
support = {PRGS/1/2023/ICT02/UIAM/02/1//Ministry of Higher Education Malaysia/ ; },
mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; *Fractals ; *Macular Degeneration/diagnosis ; *Glaucoma/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; Reproducibility of Results ; },
}
@article {pmid38752912,
year = {2024},
author = {Shaheen, A and Ashkenazy, N and Magraner, M and Patel, NA and Fortun, J and Rosenfeld, PJ and Schwartz, SG and Haddock, LJ and Dubovy, SR and Sridhar, J and Yehoshua, Z and Kovach, JL and Townsend, JH and Smiddy, WE and Flynn, HW and Yannuzzi, NA},
title = {Faricimab in Previously Treated Eyes With Neovascular Age-Related Macular Degeneration: An Assessment of Durability and Treatment Outcomes.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {9},
pages = {504-509},
doi = {10.3928/23258160-20240410-04},
pmid = {38752912},
issn = {2325-8179},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Intravitreal Injections ; *Tomography, Optical Coherence/methods ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Visual Acuity ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Treatment Outcome ; Follow-Up Studies ; Fluorescein Angiography/methods ; Ranibizumab/administration &amp; dosage/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Immunoglobulin Fab Fragments/therapeutic use/administration &amp; dosage ; },
abstract = {BACKGROUND AND OBJECTIVE: This study evaluated the efficacy and durability of faricimab in patients with neovascular age-related macular degeneration (nAMD) who were previously treated with anti-vascular endothelial growth factor (anti-VEGF) agents.<br><br>PATIENTS AND METHODS: This retrospective case series was conducted at a single tertiary center in the United States. It focused on nAMD patients who transitioned to faricimab after initial anti-VEGF therapy, with a follow-up period of at least 9 months. "Complete dryness" was defined as the absence of intra- and/or subretinal fluid on optical coherence tomography. Durability was gauged by the extension of treatment intervals relative to the injection frequency of the previous agent.<br><br>RESULTS: Sixty-two eyes from 62 patients were included. Treatment interval ranged from 5 to 10 weeks; 10 (16%) patients were able to be extended by 2 or more weeks compared to their previous regimen. Median (interquartile range [IQR]) central field thickness was 310 &#x3bc;m (254, 376) on initiating faricimab and declined by the ninth month (P values at 3, 6, and 9 months were 0.01, 0.02, and 0.07, respectively). Median (IQR) visual acuity at initiation of faricimab was 0.4 (0.20, 0.50) and did not change by the ninth month. Complete anatomical dryness was present in 10 (16%) eyes before switching; 90% remained dry at 9 months. Of 52 (84%) incompletely dry eyes before switching, 15% achieved complete dryness by 9 months on faricimab.<br><br>CONCLUSIONS: Faricimab modestly improved the treatment intervals for a small proportion of previously treated patients on anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:504-509.].},
}
@article {pmid38750770,
year = {2024},
author = {Daniel, S and Hulleman, JD},
title = {Exploring ocular fibulin-3 (EFEMP1): Anatomical, age-related, and species perspectives.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1870},
number = {6},
pages = {167239},
pmid = {38750770},
issn = {1879-260X},
support = {P30 EY030413/EY/NEI NIH HHS/United States ; P51 OD011133/OD/NIH HHS/United States ; R01 EY027785/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; *Extracellular Matrix Proteins/metabolism/genetics ; *Aging/metabolism/genetics ; Retina/metabolism ; Swine ; Male ; Mice, Inbred C57BL ; Macular Degeneration/metabolism/pathology/genetics ; Retinal Pigment Epithelium/metabolism ; Female ; Species Specificity ; Aged ; },
abstract = {Fibulin-3 (FBLN3, aka EFEMP1) is a secreted extracellular matrix (ECM) glycoprotein implicated in ocular diseases including glaucoma and age-related macular degeneration. Yet surprisingly, little is known about its native biology, expression patterns, and localization in the eye. To overcome these shortcomings, we conducted gene expression analysis and immunohistochemistry for FBLN3 in ocular tissues from mice, pigs, non-human primates, and humans. Moreover, we evaluated age-related changes in FBLN3 and FBLN3-related ECM remodeling enzymes/inhibitors in aging mice. We found that FBLN3 displayed distinct staining patterns consistent across the mouse retina, particularly in the ganglion cell layer and inner nuclear layer (INL). In contrast, human retinas exhibited a unique staining pattern, with enrichment of FBLN3 in the retinal pigment epithelium (RPE), INL, and outer nuclear layer (ONL) in the peripheral retina. This staining transitioned to the outer plexiform layer (OPL) in the central retina/macula, and was accompanied by reduced RPE immunoreactivity approaching the fovea. Surprisingly, we found significant age-related increases in FBLN3 expression and protein abundance in the mouse retina which was paralleled by reduced transcript levels of FBLN3-degrading enzymes (i.e., Mmp2 and Htra1). Our findings highlight important species-dependent, retinal region-specific, and age-related expression and localization patterns of FBLN3 which favor its accumulation during aging. These findings contribute to a better understanding of FBLN3's role in ocular pathology and provide valuable insights for future FBLN3 research.},
}
@article {pmid38749531,
year = {2024},
author = {Cheong, KX and Zhang, C and Tan, TE and Fenner, BJ and Wong, WM and Teo, KY and Wang, YX and Sivaprasad, S and Keane, PA and Lee, CS and Lee, AY and Cheung, CMG and Wong, TY and Cheong, YG and Song, SJ and Tham, YC},
title = {Comparing generative and retrieval-based chatbots in answering patient questions regarding age-related macular degeneration and diabetic retinopathy.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {10},
pages = {1443-1449},
pmid = {38749531},
issn = {1468-2079},
support = {R01 AG060942/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; Cross-Sectional Studies ; *Macular Degeneration/physiopathology ; Surveys and Questionnaires ; Female ; Male ; Patient Education as Topic/methods ; },
abstract = {BACKGROUND/AIMS: To compare the performance of generative versus retrieval-based chatbots in answering patient inquiries regarding age-related macular degeneration (AMD) and diabetic retinopathy (DR).<br><br>METHODS: We evaluated four chatbots: generative models (ChatGPT-4, ChatGPT-3.5 and Google Bard) and a retrieval-based model (OcularBERT) in a cross-sectional study. Their response accuracy to 45 questions (15 AMD, 15 DR and 15 others) was evaluated and compared. Three masked retinal specialists graded the responses using a three-point Likert scale: either 2 (good, error-free), 1 (borderline) or 0 (poor with significant inaccuracies). The scores were aggregated, ranging from 0 to 6. Based on majority consensus among the graders, the responses were also classified as 'Good', 'Borderline' or 'Poor' quality.<br><br>RESULTS: Overall, ChatGPT-4 and ChatGPT-3.5 outperformed the other chatbots, both achieving median scores (IQR) of 6 (1), compared with 4.5 (2) in Google Bard, and 2 (1) in OcularBERT (all p &#x2264;8.4&#xd7;10[-3]). Based on the consensus approach, 83.3% of ChatGPT-4's responses and 86.7% of ChatGPT-3.5's were rated as 'Good', surpassing Google Bard (50%) and OcularBERT (10%) (all p &#x2264;1.4&#xd7;10[-2]). ChatGPT-4 and ChatGPT-3.5 had no 'Poor' rated responses. Google Bard produced 6.7% Poor responses, and OcularBERT produced 20%. Across question types, ChatGPT-4 outperformed Google Bard only for AMD, and ChatGPT-3.5 outperformed Google Bard for DR and others.<br><br>CONCLUSION: ChatGPT-4 and ChatGPT-3.5 demonstrated superior performance, followed by Google Bard and OcularBERT. Generative chatbots are potentially capable of answering domain-specific questions outside their original training. Further validation studies are still required prior to real-world implementation.},
}
@article {pmid38748934,
year = {2024},
author = {Khan, AH and Lotery, AJ},
title = {Central Serous Chorioretinopathy: Epidemiology, Genetics and Clinical Features.},
journal = {Annual review of vision science},
volume = {10},
number = {1},
pages = {477-505},
doi = {10.1146/annurev-vision-102122-102907},
pmid = {38748934},
issn = {2374-4650},
mesh = {Humans ; *Central Serous Chorioretinopathy/epidemiology/genetics/diagnosis ; Genetic Predisposition to Disease ; Risk Factors ; Fluorescein Angiography ; Tomography, Optical Coherence ; Multimodal Imaging ; },
abstract = {Central serous chorioretinopathy (CSCR) is the fourth most common medical retinal disease. Moderate vision loss occurs in approximately one-third of patients who have the chronic form of the disease. CSCR has a multifactorial etiology, with acquired risk factors and increasing evidence of genetic susceptibility factors. The detection of new gene variants in CSCR and association of these variants with age-related macular degeneration provide insights into possible disease mechanisms. The contribution of multimodal ocular imaging and associated research studies to the modern-day clinical investigation of CSCR has been significant. This review aims to provide an overview of the most significant epidemiological and genetic studies of CSCR, in addition to describing its clinical and multimodal imaging features. The review also provides an update of the latest evidence from studies investigating pathophysiological mechanisms in CSCR and current opinions on multimodal imaging to better classify this complex retinal disease.},
}
@article {pmid38746430,
year = {2024},
author = {Brinkmeier, ML and Wang, SQ and Pittman, H and Cheung, LY and Prasov, L},
title = {Myelin regulatory factor (Myrf) is a critical early regulator of retinal pigment epithelial development.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.04.26.591281},
pmid = {38746430},
issn = {2692-8205},
abstract = {UNLABELLED: Myelin regulatory factor (Myrf) is a critical transcription factor in early retinal and retinal pigment epithelial development, and human variants in MYRF are a cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed on Myrf conditional knockout mice (Rx>Cre Myrf [fl/fl]) at 3 developmental timepoints. Myrf was expressed specifically in the RPE, and expression was abrogated in Rx>Cre Myrf [fl/fl] eyes. scRNAseq analysis revealed a loss of RPE cells at all timepoints resulting from cell death. GO-term analysis in the RPE revealed downregulation of melanogenesis and anatomic structure morphogenesis pathways, which were supported by electron microscopy and histologic analysis. Novel structural target genes including Ermn and Upk3b , along with macular degeneration and inherited retinal disease genes were identified as downregulated, and a strong upregulation of TGFß/BMP signaling and effectors was observed. Regulon analysis placed Myrf downstream of Pax6 and Mitf and upstream of Sox10 in RPE differentiation. Together, these results suggest a strong role for Myrf in the RPE maturation by regulating melanogenesis, cell survival, and cell structure, in part acting through suppression of TGFß signaling and activation of Sox10 .<br><br>SUMMARY STATEMENT: Myrf regulates RPE development, melanogenesis, and is important for cell structure and survival, in part through regulation of Ermn , Upk3b and Sox10, and BMP/TGFb signaling.},
}
@article {pmid38745648,
year = {2024},
author = {Zhang, L and Li, Y and Wu, Z and Shen, Q and Zeng, C and Liu, H and Zhang, X and Yang, J and Liu, Q and Tang, D and Ou, K and Fang, Y},
title = {Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1/NF-κB signaling pathway.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1379586},
pmid = {38745648},
issn = {1664-3224},
mesh = {*Choroidal Neovascularization/metabolism/pathology/genetics ; Animals ; *Signal Transduction ; Mice ; Humans ; *NF-kappa B/metabolism ; Ubiquitin Thiolesterase/genetics/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Macrophages/metabolism/immunology ; Choroid/metabolism/pathology/blood supply ; Male ; Wet Macular Degeneration/metabolism/genetics/pathology ; Inflammation/metabolism ; Cytokines/metabolism ; },
abstract = {OBJECTIVE: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression.<br><br>METHODS: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis.<br><br>RESULTS: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-&#x3ba;B signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis.<br><br>CONCLUSION: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-&#x3ba;B signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.},
}
@article {pmid38745035,
year = {2024},
author = {Jiang, B and Wei, X and Cai, D and Wang, X and Zhou, X and Chen, F and Shen, X and Cao, X and Zheng, C},
title = {Association between dietary consumption of fatty acids and age-related macular degeneration in the National Health and Nutrition Examination Survey.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11016},
pmid = {38745035},
issn = {2045-2322},
support = {[2023]-40//Guizhou Provincial People's Hospital Talent Fund/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; Male ; Female ; *Nutrition Surveys ; Middle Aged ; Aged ; Cross-Sectional Studies ; *Fatty Acids/administration &amp; dosage ; United States/epidemiology ; Dietary Fats/administration &amp; dosage ; Adult ; Diet ; Eicosapentaenoic Acid/administration &amp; dosage ; },
abstract = {The aim of this study is to assess the relationship between dietary intake of fatty acids and the age-related macular degeneration (AMD) in the United States population. Adult participants of the 2005-2008 National Health and Nutrition Examination Survey (NHANES) were included in this nationwide cross-sectional study. Dietary fatty acid intake was obtained from two 24-h dietary recall interviews. The intake of dietary fatty acids was analyzed as a continuous and categorical variable. AMD status was assessed using nonmydriatic fundus photographs. Univariate and multivariate logistic regression analyses were used to assess the association between dietary fatty acid intake and AMD. The unweighted population included 4702 individuals of whom 374 had AMD. After adjusting for relevant variables, each 1 unit increase (1 mg/1000 kcal) intake of EPA (OR: 0.996, 95% CI: 0.993-0.996, P = 0.018), DPA (OR: 0.976, 95% CI: 0.962-0.990, P = 0.002), and DHA (OR: 0.996, 95% CI: 0.994-0.999, P = 0.003) were significantly decreased odds of any AMD. The highest versus lowest quartile of EPA (OR: 0.476, P for trend < 0.001), DPA (OR: 0.467, P for trend = 0.005) and DHA (OR: 0.586, P for trend = 0.008) were negatively associated with the odds of any AMD. Subgroup analysis showed that higher quartiles of EPA (OR: 0.461, P for trend < 0.002), DPA (OR: 0.467, P for trend = 0.006) and DHA (OR: 0.578, P for trend = 0.007) exhibited a negative association with early AMD. The study found no significant association between the intake of dietary fatty acids, including n-3 PUFA, and the odds of late AMD. In the 2005-2008 NHANES population, higher dietary DHA, DPA and EPA intake associated with decreased odds of early AMD. However, no clear association was found between specific types of FAs and late AMD.},
}
@article {pmid38744794,
year = {2024},
author = {Zhang, R and Wang, L and Li, Y and Liu, Y and Dong, K and Pei, Y and Zhao, J and Liu, G and Li, J and Zhang, X and Cui, T and Gao, Y and Wang, W and Wang, Y and Gui, C and Zhou, G},
title = {CYTOR-NFAT1 feedback loop regulates epithelial-mesenchymal transition of retinal pigment epithelial cells.},
journal = {Human cell},
volume = {37},
number = {4},
pages = {1056-1069},
pmid = {38744794},
issn = {1749-0774},
support = {202203021212071//Natural Science Foundation for Young Scientists of Shanxi Province/ ; 2023ZYYC053//Scientific Research Project of Shanxi Administration of Traditional Chinese Medicine/ ; Q202201//Graduate Education Innovation Project of Shanxi Province/ ; },
mesh = {*Epithelial-Mesenchymal Transition/genetics ; Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *NFATC Transcription Factors/metabolism/genetics ; *RNA, Long Noncoding/physiology/genetics/metabolism ; *Macular Degeneration/genetics/metabolism/pathology/etiology ; *Feedback, Physiological ; Gene Expression/genetics ; Cell Proliferation/genetics ; Cell Movement/genetics ; Transforming Growth Factor beta1/metabolism ; Signal Transduction/genetics/physiology ; Epithelial Cells/metabolism ; Cell Line ; Cells, Cultured ; },
abstract = {Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-β1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD.},
}
@article {pmid38743415,
year = {2024},
author = {},
title = {Erratum in: Age-Related Macular Degeneration Choroidal Vascular Distribution Characteristics Based on Indocyanine Green Angiography.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {5},
pages = {23},
doi = {10.1167/iovs.65.5.23},
pmid = {38743415},
issn = {1552-5783},
}
@article {pmid38742956,
year = {2024},
author = {Luo, S and Hu, Q and Jiang, B and Zhang, Z and Sun, D},
title = {Bioinformatics analysis for constructing a cellular senescence-related age-related macular degeneration diagnostic model and identifying relevant disease subtypes to guide treatment.},
journal = {Aging},
volume = {16},
number = {9},
pages = {8044-8069},
pmid = {38742956},
issn = {1945-4589},
mesh = {*Cellular Senescence/genetics ; *Macular Degeneration/genetics/diagnosis/pathology ; Humans ; *Computational Biology ; Gene Regulatory Networks ; Gene Expression Profiling ; Machine Learning ; MicroRNAs/genetics/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a condition causing progressive central vision loss. Growing evidence suggests a link between cellular senescence and AMD. However, the exact mechanism by which cellular senescence leads to AMD remains unclear. Employing machine learning, we established an AMD diagnostic model. Through unsupervised clustering, two distinct AMD subtypes were identified. GO, KEGG, and GSVA analyses explored the diverse biological functions associated with the two subtypes. By WGCNA, we constructed a coexpression network of differential genes between the subtypes, revealing the regulatory role of hub genes at the level of transcription factors and miRNAs. We identified 5 genes associated with inflammation for the construction of the AMD diagnostic model. Additionally, we observed that the level of cellular senescence and pathways related to programmed cell death (PCD), such as ferroptosis, necroptosis, and pyroptosis, exhibited higher expression levels in subtype B than A. Immune microenvironments also differed between the subtypes, indicating potentially distinct pathogenic mechanisms and therapeutic targets. In summary, by leveraging cellular senescence-associated gene expression, we developed an AMD diagnostic model. Furthermore, we identified two subtypes with varying expression patterns of senescence genes, revealing their differential roles in programmed cell death, disease progression, and immune microenvironments within AMD.},
}
@article {pmid38742929,
year = {2024},
author = {Bergmans, S and Noel, NCL and Masin, L and Harding, EG and Krzywańska, AM and De Schutter, JD and Ayana, R and Hu, CK and Arckens, L and Ruzycki, PA and MacDonald, RB and Clark, BS and Moons, L},
title = {Age-related dysregulation of the retinal transcriptome in African turquoise killifish.},
journal = {Aging cell},
volume = {23},
number = {8},
pages = {e14192},
pmid = {38742929},
issn = {1474-9726},
support = {DP2 AG077431/AG/NIA NIH HHS/United States ; P30 EY002687/EY/NEI NIH HHS/United States ; //KU Leuven/ ; //Fonds Wetenschappelijk Onderzoek/ ; //Moorfields Eye Charity/ ; //BrightFocus Foundation/ ; //Research to Prevent Blindness/ ; /EY/NEI NIH HHS/United States ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Animals ; *Transcriptome/genetics ; *Retina/metabolism/pathology ; *Aging/genetics ; Fundulidae/genetics ; Killifishes ; },
abstract = {Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNAseq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age-related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterized, confirming the presence of all typical vertebrate retinal cell types. Data integration from age-matched samples between the bulk and scRNAseq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasizes the value of the fast-ageing killifish in elucidating molecular signatures in age-associated retinal disease and vision decline. This study contributes to the understanding of how age-related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age-related pathologies.},
}
@article {pmid38739943,
year = {2024},
author = {Rajala, A and Rajala, RVS},
title = {Age-Related Changes in the Glycolytic Enzymes of M2-Isoform of Pyruvate Kinase and Fructose-1,6-Bisphosphate Aldolase: Implications to Age-Related Macular Degeneration.},
journal = {Aging and disease},
volume = {15},
number = {5},
pages = {2271-2283},
pmid = {38739943},
issn = {2152-5250},
support = {P30 EY021725/EY/NEI NIH HHS/United States ; R01 EY000871/EY/NEI NIH HHS/United States ; R01 EY030024/EY/NEI NIH HHS/United States ; R01 EY035282/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Pyruvate Kinase/metabolism/genetics ; *Macular Degeneration/metabolism/pathology/genetics ; *Fructose-Bisphosphate Aldolase/metabolism/genetics ; Mice ; *Glycolysis ; *Retinal Pigment Epithelium/metabolism/enzymology ; Aging/metabolism ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; },
abstract = {Prior studies have emphasized a bioenergetic crisis in the retinal pigment epithelium (RPE) as a critical factor in the development of age-related macular degeneration (AMD). The isoforms Fructose-1,6-bisphosphate aldolase C (ALDOC) and pyruvate kinase M2 (PKM2) have been proposed to play a role in AMD pathogenesis. While PKM2 and ALDOC are crucial for aerobic glycolysis in the neural retina, they are not as essential for the RPE. In this study, we examined the expression and activity of PKM2 and ALDOC in both young and aged RPE cells, as well as in the retina and RPE tissue of mice, including an experimentally induced AMD mouse model. Our findings reveal an upregulation in PKM2 and ALDOC expression, accompanied by increased pyruvate kinase activity, in the aged and AMD mouse RPE. Conversely, there is a decrease in ALDOC expression but an increase in PKM2 expression and pyruvate kinase activity in the aged and AMD retina. Overall, our study indicates that aged and AMD RPE cells tend to favor aerobic glycolysis, while this tendency is diminished in the aged and AMD retina. These results underscore the significance of targeting PKM2 and ALDOC in the RPE as a promising therapeutic approach to address the bioenergetic crisis and prevent vision loss in AMD.},
}
@article {pmid38739167,
year = {2024},
author = {Maruyama-Inoue, M and Chin, JY and Kadonosono, K},
title = {Response to letter to the editor Re: comment on "Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration".},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3735-3736},
pmid = {38739167},
issn = {1435-702X},
}
@article {pmid38739148,
year = {2024},
author = {Smirnova, TV and Budzinskaya, MV and Sheludchenko, VM},
title = {[Multifocal electroretinography in the diagnosis and monitoring of early and intermediate stages of age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {2. Vyp. 2},
pages = {172-179},
doi = {10.17116/oftalma2024140022172},
pmid = {38739148},
issn = {0042-465X},
mesh = {Humans ; *Electroretinography/methods ; *Macular Degeneration/diagnosis/physiopathology ; *Retina/diagnostic imaging/physiopathology ; Tomography, Optical Coherence/methods ; Visual Acuity ; Early Diagnosis ; Disease Progression ; },
abstract = {Multifocal electroretinography is a valuable diagnostic method for the objective localization and quantitative assessment of functional disorders of the central retina in age-related macular degeneration. It is used to detect early changes, monitor the course of the disease and treatment outcomes. In many cases, multifocal electroretinography is a more sensitive method for detecting functional disorders at the early/intermediate stage of age-related macular degeneration compared to morphological (optical coherence tomography) and subjective (visual acuity, perimetry) testing methods.},
}
@article {pmid38739137,
year = {2024},
author = {Stoyukhina, AS and Korobov, EN and Smolin, SA},
title = {[Isolated primary vitreoretinal lymphoma (case report)].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {2. Vyp. 2},
pages = {94-101},
doi = {10.17116/oftalma202414002294},
pmid = {38739137},
issn = {0042-465X},
mesh = {Humans ; *Vitreous Body/pathology/diagnostic imaging ; *Retinal Neoplasms/diagnosis ; *Tomography, Optical Coherence/methods ; Diagnosis, Differential ; Intraocular Lymphoma/diagnosis ; Male ; Myeloid Differentiation Factor 88/genetics ; Fluorescein Angiography/methods ; Aged ; Eye Neoplasms/diagnosis ; },
abstract = {This case report presents the diagnostic features of isolated primary intraocular lymphoma, which was initially misdiagnosed as neovascular age-related macular degeneration. A comprehensive examination using ultrasound, optical coherence tomography, and fundus autofluorescence revealed changes characteristic of vitreoretinal lymphoma. Molecular genetic analysis of the vitreous body showed the presence of a MYD88 gene mutation and B-cell clonality by immunoglobulin heavy chain (IGH) gene rearrangement tests, which confirmed the diagnosis.},
}
@article {pmid38739134,
year = {2024},
author = {Andreeva, YS and Alkharki, L and Shelankova, AV and Budzinskaya, MV},
title = {[Topical application of hypotensive drugs for the prevention of intraocular pressure elevation after intravitreal injections of anti-VEGF drugs].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {2. Vyp. 2},
pages = {73-79},
doi = {10.17116/oftalma202414002273},
pmid = {38739134},
issn = {0042-465X},
mesh = {Humans ; Male ; *Intravitreal Injections ; Female ; Aged ; *Intraocular Pressure/drug effects ; *Ocular Hypertension/prevention &amp; control/drug therapy/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; Prospective Studies ; *Sulfonamides/administration &amp; dosage ; Treatment Outcome ; Antihypertensive Agents/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Tonometry, Ocular/methods ; Middle Aged ; Timolol/administration &amp; dosage ; Brimonidine Tartrate/administration &amp; dosage ; Ophthalmic Solutions/administration &amp; dosage ; Thiazines/administration &amp; dosage ; Macular Degeneration/drug therapy/diagnosis ; },
abstract = {UNLABELLED: The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice.<br><br>PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD.<br><br>MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection.<br><br>RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001).<br><br>CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.},
}
@article {pmid38739128,
year = {2024},
author = {Alkharki, L and Yusef, SN and Al-Makhdar, YM and Andreeva, IV and Matyuschenko, AG and Gerasimov, AN and Budzinskaya, MV},
title = {[Application of optical coherence tomography in the assessment of the posterior lens capsule during anti-angiogenic therapy].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {2. Vyp. 2},
pages = {28-33},
doi = {10.17116/oftalma202414002228},
pmid = {38739128},
issn = {0042-465X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Aged ; *Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; Posterior Capsule of the Lens/diagnostic imaging/drug effects ; Middle Aged ; Macular Degeneration/drug therapy/diagnosis ; },
abstract = {UNLABELLED: Intravitreal injection (IVI) of anti-angiogenic drugs is one of the most common therapeutic procedures in ophthalmology. In recent years, a new non-contact study method has been developed - anterior segment optical coherence tomography (AS-OCT), which allows the formation of three-dimensional images of the lens and provides more detailed information about its structure and morphology.<br><br>PURPOSE: This study uses optical coherence tomography method to analyze the risks of developing changes in the posterior lens capsule in patients after IVI of an anti-angiogenic drug.<br><br>MATERIAL AND METHODS: The study involved 100 people (14 men and 86 women) with a natural lens and neovascular age-related macular degeneration (nAMD). The average age was 70.57&#xb1;7.98 years. During the study (12 months), all patients underwent IVI of an anti-angiogenic drug aflibercept in the treat-and-extend (T&amp;E) mode. All subjects were divided into 2 groups: with a total number of IVI less than 10 - group 1 (50 patients), and more than 10 IVI - group 2 (50 patients, of which 49 were included in the study). All patients underwent OCT using the Optopol REVO NX device (Poland) with the Anterior B-scan Wide protocol before inclusion in the study, as well as after 3, 6 and 12 months.<br><br>RESULTS: It was found that the risk of developing a posterior lens capsule rupture, visualized using OCT, depends on the total number of IVI (correlation coefficient 0.473 p=0.001): the more IVI, the higher the probability that damage to the posterior capsule will occur after the next IVI, and after the 15th injection the risk of developing damage to the posterior capsule increases sharply.<br><br>CONCLUSION: The astudy analyzed the risk factors for the development of posterior lens capsule damage that can be detected using OCT, and presented three risk groups for the development of rupture (or damage) of the posterior lens capsule depending on the number of intravitreal injections performed.},
}
@article {pmid38739125,
year = {2024},
author = {Andreeva, YS and Alkharki, L and Budzinskaya, MV},
title = {[Changes in intraocular pressure and biometric parameters of the anterior segment of the eye after intravitreal injections].},
journal = {Vestnik oftalmologii},
volume = {140},
number = {2. Vyp. 2},
pages = {7-15},
doi = {10.17116/oftalma20241400227},
pmid = {38739125},
issn = {0042-465X},
mesh = {*Intraocular Pressure/drug effects ; *Anterior Eye Segment/diagnostic imaging/drug effects ; Intravitreal Injections ; Tomography, Optical Coherence ; *Lenses, Intraocular ; *Lens, Crystalline ; *Macular Degeneration/drug therapy ; Humans ; Male ; Female ; Middle Aged ; Aged ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs.<br><br>MATERIAL AND METHODS: The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro.<br><br>RESULTS: In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0&#xb0;-180&#xb0; before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9&#xb1;9.3&#xb0; (p<0.001) and 16.9&#xb1;8.2&#xb0; (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group.<br><br>CONCLUSIONS: AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.},
}
@article {pmid38738646,
year = {2025},
author = {Wong, KY and Wong, MS and Liu, J},
title = {Nanozymes for Treating Ocular Diseases.},
journal = {Advanced healthcare materials},
volume = {14},
number = {8},
pages = {e2401309},
pmid = {38738646},
issn = {2192-2659},
mesh = {Humans ; *Eye Diseases/drug therapy ; Animals ; Nanomedicine/methods ; Antioxidants/therapeutic use/chemistry ; *Nanoparticles/chemistry/therapeutic use ; Anti-Inflammatory Agents/therapeutic use/chemistry ; *Nanostructures/chemistry/therapeutic use ; Macular Degeneration/drug therapy ; },
abstract = {Nanozymes, characterized by their nanoscale size and enzyme-like catalytic activities, exhibit diverse therapeutic potentials, including anti-oxidative, anti-inflammatory, anti-microbial, and anti-angiogenic effects. These properties make them highly valuable in nanomedicine, particularly ocular therapy, bypassing the need for systemic delivery. Nanozymes show significant promise in tackling multi-factored ocular diseases, particularly those influenced by oxidation and inflammation, like dry eye disease, and age-related macular degeneration. Their small size, coupled with their ease of modification and integration into soft materials, facilitates the effective penetration of ocular barriers, thereby enabling targeted or prolonged therapy within the eye. This review is dedicated to exploring ocular diseases that are intricately linked to oxidation and inflammation, shedding light on the role of nanozymes in managing these conditions. Additionally, recent studies elucidating advanced applications of nanozymes in ocular therapeutics, along with their integration with soft materials for disease management, are discussed. Finally, this review outlines directions for future investigations aimed at bridging the gap between nanozyme research and clinical applications.},
}
@article {pmid38738427,
year = {2024},
author = {Kumar, A and Ferro Desideri, L and Ting, MYL and Anguita, R},
title = {Perspectives on the currently available pharmacotherapy for wet macular degeneration.},
journal = {Expert opinion on pharmacotherapy},
volume = {25},
number = {6},
pages = {755-767},
doi = {10.1080/14656566.2024.2354921},
pmid = {38738427},
issn = {1744-7666},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use/pharmacology/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy ; *Intravitreal Injections ; Genetic Therapy ; Drug Delivery Systems ; Animals ; Biosimilar Pharmaceuticals/therapeutic use ; Cost-Benefit Analysis ; Drug Development ; },
abstract = {INTRODUCTION: Wet age-related macular degeneration (w-AMD) is a leading cause of visual impairment globally, with its prevalence expected to rise alongside increasing life expectancy. The current standard treatment involves frequent intravitreal injections of anti-VEGF agents, which although revolutionary, pose significant burdens on both patients and healthcare services.<br><br>AREAS COVERED: This review explores current and emerging pharmaceutical treatments for w-AMD, focusing on their pharmacokinetics, pharmacodynamics, efficacy, and safety. Promising developments include extending treatment intervals with newer anti-VEGF agents like brolucizumab and faricimab, biosimilars offering cost-effective options, and exploring innovative drug delivery methods such as subretinal gene therapy. Combination therapies, gene therapies, and novel agents like KSI-301 and OPT-302 show potential for improving treatment outcomes and reducing treatment burden.<br><br>EXPERT OPINION: While current treatments for w-AMD have significantly advanced with the advent of anti-VEGF therapies, their limitations in terms of treatment burden and incomplete responses have spurred research into diverse alternative approaches. These innovative strategies offer hope for improving patient outcomes and reducing healthcare burdens, suggesting a promising future for w-AMD management.},
}
@article {pmid38738342,
year = {2025},
author = {Lee, D and Tomita, Y and Negishi, K and Kurihara, T},
title = {Retinal ischemic diseases and promising therapeutic molecular targets.},
journal = {Histology and histopathology},
volume = {40},
number = {1},
pages = {11-20},
pmid = {38738342},
issn = {1699-5848},
support = {18&#x2009;K09424//Grants-in-Aid for Scientific Research. KAKENHI/ ; 15&#x2009;K10881//Grants-in-Aid for Scientific Research. KAKENHI/ ; JPMJSP2123//JST SPRING/ ; },
mesh = {Humans ; *Ischemia/drug therapy/metabolism ; Animals ; *Retinal Diseases/drug therapy/metabolism/therapy ; PPAR alpha/metabolism ; Molecular Targeted Therapy ; NAD/metabolism ; Retinal Vessels/drug effects/pathology ; },
abstract = {Retinal ischemia is a fundamental pathologic condition associated with retinal vascular occlusion, glaucoma, diabetic retinopathy, age-related macular degeneration, and other eye diseases. Extensive inflammation, redox imbalance, apoptosis, and abnormal vascular formation in retinal ischemia could lead to visual impairments. Developing or finding effective treatments is urgently needed to protect the eye against retinal ischemia and related damage. To address the demand, we have searched for promising therapeutic molecular targets in the eye (e.g., hypoxia-inducible factor [HIF], peroxisome proliferator-activated receptor-alpha [PPARα], and nicotinamide adenine dinucleotide [NAD[+]]), and found that modulations of each molecular target might protect the eye against retinal ischemic damage in terms of complex pathologic mechanisms. In the current article, we review and update the therapeutic evidence of modulation of HIF, PPARα, or NAD[+] and discuss future directions for developing promising drugs based on these molecular targets. This summary urges research to obtain more solid evidence of each molecular target in retinal ischemic diseases.},
}
@article {pmid38737369,
year = {2024},
author = {},
title = {Faricimab for neovascular age-related macular degeneration and diabetic macular oedema.},
journal = {Australian prescriber},
volume = {47},
number = {2},
pages = {66-67},
pmid = {38737369},
issn = {0312-8008},
}
@article {pmid38736272,
year = {2024},
author = {Liu, Y and Wang, J and Yu, X and Hu, J and Sun, X},
title = {Study on the material basis of Zhujing pill in treating fundus lesions through component analysis and network pharmacology.},
journal = {Biomedical chromatography : BMC},
volume = {38},
number = {7},
pages = {e5885},
doi = {10.1002/bmc.5885},
pmid = {38736272},
issn = {1099-0801},
support = {81873083//National Natural Science Foundation of China/ ; },
mesh = {*Drugs, Chinese Herbal/chemistry/pharmacology ; *Network Pharmacology ; *Molecular Docking Simulation ; Chromatography, High Pressure Liquid/methods ; Humans ; Mass Spectrometry/methods ; },
abstract = {Zhujing pill (ZP) is a famous Chinese herbal formula that has been widely used to treat diabetic retinopathy, macular degeneration, retinitis pigmentosa and other fundus lesions. In this study, the material basis and mechanism of ZP in the treatment of fundus lesions were evaluated via the high-performance liquid chromatography fingerprint, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, network pharmacology and molecular docking. A total of 32 common components were found and 31 components were identified in 15 batches of ZP samples. Moreover, 134 common key targets and 17 putative active components that are connected to fundus lesions were identified. Molecular docking revealed that quercetin, kaempferol, isorhamnetin, 5-O-feruloylquinic acid, plantagoside and 2'-acetylacteoside have the ability to interact with the core targets such as AKT1, TP53, TNF, IL-6 and Jun. Our findings revealed that the therapeutic effects of ZP on fundus lesions are mediated by multiple components, targets and pathways, including at least six active ingredients and 11 targets. The study provides new ideas for further research on the material basis and mechanisms of traditional Chinese medicine prescriptions.},
}
@article {pmid38735629,
year = {2024},
author = {Trincão-Marques, J and Ayton, LN and Hickey, DG and Marques-Neves, C and Guymer, RH and Edwards, TL and Sousa, DC},
title = {Gene and cell therapy for age-related macular degeneration: A review.},
journal = {Survey of ophthalmology},
volume = {69},
number = {5},
pages = {665-676},
doi = {10.1016/j.survophthal.2024.05.002},
pmid = {38735629},
issn = {1879-3304},
mesh = {Humans ; *Genetic Therapy/methods ; Cell- and Tissue-Based Therapy/methods ; Macular Degeneration/therapy ; Wet Macular Degeneration/therapy/diagnosis ; Geographic Atrophy/therapy/diagnosis ; },
abstract = {Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss among the elderly in Western communities, with an estimated global prevalence of 10 - 20% in people older than 65 years. AMD leads to central vision loss due to degeneration of the photoreceptors, retinal pigment epithelium and the choriocapillaris. Beckman's classification for AMD, based upon color fundus photographs, divides the disease into early, intermediate, and late forms. The late, vision-threatening stage includes both neovascular AMD and geographic atrophy. Despite its high prevalence and impact on patients' quality of life, treatment options for AMD are limited. While neovascular AMD can be medically managed with anti-VEGF intravitreal injections, until very recently there has been no approved treatment options for atrophic AMD; however, in February 2023 the first treatment for geographic atrophy - pegcetacoplan - was approved by the US FDA. We describe the current landscape of potential gene and cell therapeutic strategies for late-stage AMD, with an emphasis on the therapeutic options that might become available in the next few years.},
}
@article {pmid38735055,
year = {2024},
author = {Shatz, N and Chohan, Y and Klionsky, DJ},
title = {ATG14 and STX18: gatekeepers of lipid droplet degradation and the implications for disease modulation.},
journal = {Autophagy},
volume = {20},
number = {8},
pages = {1697-1699},
pmid = {38735055},
issn = {1554-8635},
support = {R35 GM131919/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; Adaptor Proteins, Vesicular Transport ; Autophagy/physiology ; Autophagy-Related Proteins/metabolism ; *Lipid Droplets/metabolism ; Lipid Metabolism ; },
abstract = {Lipophagy, a form of autophagy specific to the degradation of lipid droplets (LDs), plays an important role in the maintenance of cellular homeostasis and metabolic processes. A recent study has identified ATG14 (autophagy related 14) as a molecule that targets LDs and marks them for degradation via lipophagy; a process that is inhibited by the binding of STX18 (syntaxin 18) to ATG14 in mammalian cells. The exact mechanism of regulation of lipophagy, and subsequently of cellular LD levels, is still under investigation; however, dysregulation of this process has been linked to a number of disease phenotypes. An imbalance of lipid levels can result in a wide variety of conditions depending on the cell/tissue type in which they occur. In cells of the retinal pigment epithelium, lipid accumulation can result in dry age-related macular degeneration, in hepatocytes it can result in nonalcoholic fatty liver diseases and in neural cells it can result in the pathogenesis of neurodegenerative conditions such as Alzheimer and Parkinson diseases. Based upon its wide range of implications in diseases, modulation of lipophagy is currently being further investigated for its potential as a treatment for a variety of conditions ranging from viral infection to developmental illnesses.},
}
@article {pmid38734747,
year = {2024},
author = {Beare, N},
title = {Disease latency bias and the protective effect of metformin against age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {14},
pages = {2841},
pmid = {38734747},
issn = {1476-5454},
mesh = {Humans ; *Metformin/therapeutic use ; *Macular Degeneration/prevention &amp; control/drug therapy ; Hypoglycemic Agents/therapeutic use ; },
}
@article {pmid38733136,
year = {2024},
author = {Subhi, Y and Schneider, M and Hajari, JN and la Cour, M},
title = {Injection burden and treatment intervals of aflibercept in observe-and-plan regimen for neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {7},
pages = {821-827},
doi = {10.1111/aos.16709},
pmid = {38733136},
issn = {1755-3768},
mesh = {Humans ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Intravitreal Injections ; Retrospective Studies ; Female ; Male ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged ; *Tomography, Optical Coherence/methods ; *Visual Acuity ; Follow-Up Studies ; *Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Fluorescein Angiography/methods ; Macula Lutea/pathology/diagnostic imaging ; Treatment Outcome ; Time Factors ; Dose-Response Relationship, Drug ; Registries ; Fundus Oculi ; Drug Administration Schedule ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: The Observe-and-Plan (O&amp;P) regimen allows for individualised treatment. In this study, we evaluated injection burden and intervals using aflibercept in an O&amp;P regimen for eyes with neovascular age-related macular degeneration (AMD).<br><br>METHODS: This was a retrospective registry-based study of treatment-na&#xef;ve eyes with neovascular AMD. Treatment data were compiled for 3&#x2009;years after commencement of intravitreal aflibercept therapy. We evaluated clinical consequences at the first follow-up after loading dose, the proportion of patients who obtained and kept dry macula after loading dose, number of injections and intervals between injections.<br><br>RESULTS: Data were obtained for 1103 eyes. After loading dose, 0.4% were lost to follow-up, 7.5% discontinued, 50.9% booked for further injections and 41.3% booked for monthly observations. After loading dose, the macula remained dry in 49.2% at 3&#x2009;months, 34.0% at 6&#x2009;months, 23.7% at 12&#x2009;months and 15.2% at 24&#x2009;months. For the entire population, median cumulative total number of injections was 7, 12 and 15, after 1, 2 and 3&#x2009;years, respectively. After the 3rd year, the proportion of eyes in the short 4-6&#x2009;weeks treatment interval was 51.1%, 8&#x2009;weeks interval was kept in 14.4% and the extended treatment intervals of 10 and 12&#x2009;weeks was possible in 34.4%.<br><br>CONCLUSION: After loading dose, one in two eyes required further injections. A large proportion required therapy with shorter intervals than the label-recommended 8&#x2009;weeks. The large majority of those who obtained a dry macula after loading dose turned exudative again, mostly within the first 3&#x2009;months.},
}
@article {pmid38732522,
year = {2024},
author = {Kim, JM and Choi, YJ},
title = {Myopia and Nutrient Associations with Age-Related Eye Diseases in Korean Adults: A Cross-Sectional KNHANES Study.},
journal = {Nutrients},
volume = {16},
number = {9},
pages = {},
pmid = {38732522},
issn = {2072-6643},
mesh = {Humans ; Male ; Female ; Republic of Korea/epidemiology ; Middle Aged ; Cross-Sectional Studies ; *Myopia/epidemiology/etiology ; *Nutrition Surveys ; Aged ; Prevalence ; *Macular Degeneration/epidemiology/etiology ; Adult ; Risk Factors ; *Cataract/epidemiology/etiology ; *Diet/statistics &amp; numerical data/adverse effects ; Eye Diseases/epidemiology/etiology ; Glaucoma/epidemiology/etiology ; Odds Ratio ; Nutrients ; },
abstract = {This study assessed the prevalence of myopia, cataracts, glaucoma, and macular degeneration among Koreans over 40, utilizing data from the 7th Korea National Health and Nutrition Examination Survey (KNHANES VII, 2018). We analyzed 204,973 adults (44% men, 56% women; mean age 58.70 ± 10.75 years), exploring the association between myopia and these eye diseases through multivariate logistic regression, adjusting for confounders and calculating adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results showed a myopia prevalence of 44.6%, cataracts at 19.4%, macular degeneration at 16.2%, and glaucoma at 2.3%, with significant differences across ages and genders. A potential link was found between myopia and an increased risk of cataracts and macular degeneration, but not with glaucoma. Additionally, a higher dietary intake of carbohydrates, polyunsaturated and n-6 fatty acids, vitamins, and minerals correlated with lower risks of these diseases, underscoring the importance of the diet in managing and preventing age-related eye conditions. These findings highlight the need for dietary considerations in public health strategies and confirm myopia as a significant risk factor for specific eye diseases in the aging Korean population.},
}
@article {pmid38732315,
year = {2024},
author = {Brinkmann, M and Viggiano, P and Boscia, G and Danckwardt, M and Susantija, E and Müller, T and Castellino, N and Schweighofer, J and Boscia, F and Toro, MD and El-Shabrawi, Y},
title = {Analysis of Choriocapillaris Reperfusion Topography following Faricimab Treatment for Neovascular Age-Related Macular Degeneration in Non-Treatment-Naïve Patients.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
pmid = {38732315},
issn = {2075-4418},
abstract = {To assess changes in choriocapillaris (CC) vascular density surrounding macular neovascularization (MNV) in age-related macular degeneration (AMD) when transitioning from various anti-VEGF treatments to faricimab, using optical coherence tomography angiography (OCTA). 25 eyes of 22 individuals who underwent intravitreal faricimab injections for neovascular AMD with type 1 MNV were included. OCTA images were obtained prior to (T0), after one (T1), and after three faricimab injections (T2); Noteworthy changes occurred in the first ring at T2 in comparison to T0. The percentage of CC flow deficit (FD%), FD average area (FDa), and FD number (FDn) in 5 rings (R1-R5) surrounding the dark halo around the MNV were calculated. A reduction in FD% at T2 compared to T0 (50.5 ± 10.2% at T0, 46.4 ± 10.6% at T2; p = 0.020) was seen, indicating CC reperfusion. Additionally, we observed a reduction in the average FDa (140.2 ± 172.1% at T0, 93.7 ± 101.8% at T2; p = 0.029). Our study highlights an FD% after three consecutive faricimab injections. The most pronounced effect was observed in the first ring, directly adjacent to the dark halo, suggesting a partial CC reperfusion surrounding the MNV, potentially indicating disease regression.},
}
@article {pmid38732004,
year = {2024},
author = {Delanghe, JR and Diana Di Mavungu, J and Beerens, K and Himpe, J and Bostan, N and Speeckaert, MM and Vrielinck, H and Vral, A and Van Den Broeke, C and Huizing, M and Van Aken, E},
title = {Fructosyl Amino Oxidase as a Therapeutic Enzyme in Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {25},
number = {9},
pages = {},
pmid = {38732004},
issn = {1422-0067},
support = {F2020/IOF-StarTT/034) IOF StarTT-project//IOF Ghent University/ ; },
mesh = {*Macular Degeneration/drug therapy/metabolism/pathology ; Humans ; *Glycation End Products, Advanced/metabolism ; Animals ; Swine ; Retina/metabolism/drug effects/pathology ; Amino Acid Oxidoreductases ; },
abstract = {Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.},
}
@article {pmid38731137,
year = {2024},
author = {Ban, N and Shinojima, A and Negishi, K and Kurihara, T},
title = {Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response.},
journal = {Journal of clinical medicine},
volume = {13},
number = {9},
pages = {},
pmid = {38731137},
issn = {2077-0383},
support = {15K10881//Scientific Research Support Fund/ ; 18K09424//Scientific Research Support Fund/ ; },
abstract = {Drusen are one of the most characteristic pathologies of precursor lesion of age-related macular degeneration (AMD). Drusen comprise a yellowish white substance that accumulates typically under the retinal pigment epithelium (RPE), and their constituents are lipids, complement, amyloid, crystallin, and others. In the past, many researchers have focused on drusen and tried to elucidate the pathophysiology of AMD because they believed that disease progression from early AMD to advanced AMD might be based on drusen or drusen might cause AMD. In fact, it is well established that drusen are the hallmark of precursor lesion of AMD and a major risk factor for AMD progression mainly based on their size and number. However, the existence of advanced AMD without drusen has long been recognized. For example, polypoidal choroidal vasculopathy (PCV), which comprises the majority of AMD cases in Asians, often lacks drusen. Thus, there is the possibility that drusen might be no more than a biomarker of AMD and not a cause of AMD. Now is the time to reconsider the relationship between AMD and drusen. In this review, we focus on early AMD pathogenesis based on basic research from the perspective of cholesterol metabolism and hypoxic response in the retina, and we discuss the role of drusen.},
}
@article {pmid38730462,
year = {2024},
author = {Martins, B and Pires, M and Ambrósio, AF and Girão, H and Fernandes, R},
title = {Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction.},
journal = {Journal of biomedical science},
volume = {31},
number = {1},
pages = {48},
pmid = {38730462},
issn = {1423-0127},
support = {GOAP/ Bayer//Global Ophthalmology Awards Program/ Bayer/ ; UIDB/04539/2020 and UIDP/04539/2020//Foundation for Science and Technology (FCT, Portugal)/ ; COMPETE-FEDER (POCI-01-0145-FEDER-007440)//Foundation for Science and Technology (FCT, Portugal)/ ; 2020.04811.BD//Foundation for Science and Technology (FCT, Portugal)/ ; },
mesh = {*Blood-Retinal Barrier/metabolism/physiopathology ; *Extracellular Vesicles/metabolism ; Humans ; Diabetic Retinopathy/physiopathology/metabolism ; Retinal Diseases/physiopathology/metabolism ; Macular Degeneration/physiopathology/metabolism ; Animals ; },
abstract = {Retinal degenerative diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), loom as threats to vision, causing detrimental effects on the structure and function of the retina. Central to understanding these diseases, is the compromised state of the blood-retinal barrier (BRB), an effective barrier that regulates the influx of immune and inflammatory components. Whether BRB breakdown initiates retinal distress, or is a consequence of disease progression, remains enigmatic. Nevertheless, it is an indication of retinal dysfunction and potential vision loss.The intricate intercellular dialogues among retinal cell populations remain unintelligible in the complex retinal milieu, under conditions of inflammation and oxidative stress. The retina, a specialized neural tissue, sustains a ceaseless demand for oxygen and nutrients from two vascular networks. The BRB orchestrates the exchange of molecules and fluids within this specialized region, comprising the inner BRB (iBRB) and the outer BRB (oBRB). Extracellular vesicles (EVs) are small membranous structures, and act as messengers facilitating intercellular communication in this milieu.EVs, both from retinal and peripheral immune cells, increase complexity to BRB dysfunction in DR and AMD. Laden with bioactive cargoes, these EVs can modulate the retinal microenvironment, influencing disease progression. Our review delves into the multifaceted role of EVs in retinal degenerative diseases, elucidating the molecular crosstalk they orchestrate, and their microRNA (miRNA) content. By shedding light on these nanoscale messengers, from their biogenesis, release, to interaction and uptake by target cells, we aim to deepen the comprehension of BRB dysfunction and explore their therapeutic potential, therefore increasing our understanding of DR and AMD pathophysiology.},
}
@article {pmid38729610,
year = {2024},
author = {Qi, J and Li, H and Du, Y and Liu, Y and He, W and Meng, J and Wei, L and Zhang, K and Lu, Y and Zhu, X},
title = {Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia.},
journal = {Molecular &amp; cellular proteomics : MCP},
volume = {23},
number = {6},
pages = {100783},
pmid = {38729610},
issn = {1535-9484},
mesh = {Humans ; *Autoantibodies/immunology/blood ; *Retinal Pigment Epithelium/pathology/metabolism ; *Autoimmunity ; Male ; Female ; Immunoglobulin G/immunology/blood ; Middle Aged ; Myopia, Degenerative/immunology ; Myopia/immunology ; Adult ; },
abstract = {High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.},
}
@article {pmid38729254,
year = {2024},
author = {Peng, ZQ and Guan, XH and Yu, ZP and Wu, J and Han, XH and Li, MH and Qu, XH and Chen, ZP and Han, XJ and Wang, XY},
title = {Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway.},
journal = {Experimental eye research},
volume = {244},
number = {},
pages = {109919},
doi = {10.1016/j.exer.2024.109919},
pmid = {38729254},
issn = {1096-0007},
mesh = {*Oxidative Stress ; Humans ; *Mesenchymal Stem Cells/metabolism ; *Exosomes/metabolism ; *Amnion/cytology ; Culture Media, Conditioned/pharmacology ; *Phosphatidylinositol 3-Kinases/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; *Retinal Degeneration/metabolism/pathology/etiology ; *Signal Transduction ; *Forkhead Box Protein O3/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; Apoptosis ; Cells, Cultured ; Reactive Oxygen Species/metabolism ; Membrane Potential, Mitochondrial ; Blotting, Western ; Animals ; Cell Survival ; Hydrogen Peroxide/toxicity ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.},
}
@article {pmid38727918,
year = {2024},
author = {Ribatti, D and Dammacco, R},
title = {Mast cells in human choroid and their role in age-related macular degeneration (AMD).},
journal = {Clinical and experimental medicine},
volume = {24},
number = {1},
pages = {98},
pmid = {38727918},
issn = {1591-9528},
mesh = {Humans ; *Mast Cells ; *Choroid/pathology ; *Macular Degeneration/pathology/metabolism ; Choroidal Neovascularization/pathology/metabolism ; Bruch Membrane/pathology/metabolism ; },
abstract = {The role of mast cells in physiologic and pathological processes extends far beyond the allergy processes: they are involved in wound healing, chronic inflammation, and tumor growth. This short article emphasizes the role played by mast cells in age-related macular degeneration (AMD). Mast cells can induce angiogenesis and are present around Bruch's membrane during the early and late stages of choroidal neovascularization in AMD. Proteolytic enzymes released by mast cells lead to thinning of the choroid in AMD as well as degradation of vascular basement membranes and Bruch's membrane, which in turn could result in retinal pigment epithelial death and choriocapillaris degeneration in geographical atrophy and exudative AMD.},
}
@article {pmid38726752,
year = {2024},
author = {Abbasi, N and O'Neill, H},
title = {Cytocompatibility of electrospun poly-L-lactic acid membranes for Bruch's membrane regeneration using human embryonic stem cell-derived retinal pigment epithelial cells.},
journal = {Journal of biomedical materials research. Part A},
volume = {112},
number = {11},
pages = {1902-1920},
doi = {10.1002/jbm.a.37736},
pmid = {38726752},
issn = {1552-4965},
support = {APP11867//National Health and Medical Research Council of Australia/ ; },
mesh = {Humans ; *Polyesters/chemistry ; *Bruch Membrane/cytology ; *Retinal Pigment Epithelium/cytology/metabolism ; *Human Embryonic Stem Cells/cytology/metabolism/drug effects ; Cell Proliferation/drug effects ; Membranes, Artificial ; Regeneration/drug effects ; Laminin/chemistry ; Biocompatible Materials/chemistry/pharmacology ; Materials Testing ; Epithelial Cells/cytology/metabolism/drug effects ; Porosity ; Polymers/chemistry/pharmacology ; Lactic Acid/chemistry/pharmacology ; Nanofibers/chemistry ; Cell Line ; Cell Differentiation/drug effects ; Peptides ; },
abstract = {Cell replacement therapy is under development for dry age-related macular degeneration (AMD). A thin membrane resembling the Bruch's membrane is required to form a cell-on-membrane construct with retinal pigment epithelial (RPE) cells. These cells have been differentiated from human embryonic stem cells (hESCs) in vitro. A carrier membrane is required for cell implantation, which is biocompatible for cell growth and has dimensions and physical properties resembling the Bruch's membrane. Here a nanofiber electrospun poly-L-lactic acid (PLLA) membrane is tested for capacity to support cell growth and maturation. The requirements for laminin coating of the membrane are identified here. A porous electrospun nanofibrous PLLA membrane of ∼50 nm fiber diameter was developed as a prototype support for functional RPE cells grown as a monolayer. The need for laminin coating applied to the membrane following treatment with poly-L-ornithine (PLO), was identified in terms of cell growth and survival. Test membranes were compared in terms of hydrophilicity after laminin coating, mechanical properties of surface roughness and Young's modulus, porosity and ability to promote the attachment and proliferation of hESC-RPE cells in culture for up to 8 weeks. Over this time, RPE cell proliferation, morphology, and marker and gene expression, were monitored. The functional capacity of cell monolayers was identified in terms of transepithelial electrical resistance (TEER), phagocytosis of cells, as well as expression of the cytokines, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). PLLA polymer fibers are naturally hydrophobic, so their hydrophilicity was improved by pretreatment with PLO for subsequent coating with the bioactive protein laminin. They were then assessed for amount of laminin adsorbed, contact angle and uniformity of coating using scanning electron microscopy (SEM). Pretreatment with 100% PLO gave the best result over 10% PLO treatment or no treatment prior to laminin adsorption with significantly greater surface stiffness and modulus. By 6 weeks after cell plating, the coated membranes could support a mature RPE monolayer showing a dense apical microvillus structure and pigmented 3D polygonal cell morphology. After 8 weeks, PLO (100%)-Lam coated membranes exhibited the highest cell number, cell proliferation, and RPE barrier function measured as TEER. RPE cells showed the higher levels of specific surface marker and gene expression. Microphthalmia-associated transcription factor expression was highly upregulated indicating maturation of cells. Functionality of cells was indicated by expression of VEGF and PEDF genes as well as phagocytic capacity. In conclusion, electrospun PLLA membranes coated with PLO-Lam have the physical and biological properties to support the distribution and migration of hESC-RPE cells throughout the whole structure. They represent a good membrane candidate for preparation of hESC-RPE cells as a monolayer for implantation into the subretinal space of AMD patients.},
}
@article {pmid38725692,
year = {2024},
author = {Nebbioso, M and Franzone, F and Milanese, A and Artico, M and Taurone, S and La Cava, M and Livani, ML and Bonfiglio, V and Vestri, A},
title = {Psychophysical, electrofunctional, and morphological evaluation in naïve neovascular AMD patients treated with intravitreal anti-VEGF.},
journal = {Aging medicine (Milton (N.S.W))},
volume = {7},
number = {2},
pages = {189-201},
pmid = {38725692},
issn = {2475-0360},
abstract = {OBJECTIVES: The aim of this study was to investigate the retinal morpho-functional characteristics of patients with neovascular wet age-related macular degeneration (nAMD) treated with intravitreal injection (IV) of aflibercept (AFL).<br><br>METHODS: The study was conducted on 35 patients previously diagnosed with type 1 nAMD who received a fixed-dosing regimen of aflibercept injections over 12&#x2009;months. The goal was to assess trends in visual abilities over time by measuring visual acuity (VA), contrast sensitivity (CS), visual evoked potentials (VEPs), and spectral domain-optical coherence tomography (SD-OCT). The same psychophysical, electro-functional, and morphological tests administered at baseline (T0) were repeated 4 to 8&#x2009;weeks after the last aflibercept injection (Tn), resulting in a total of six examinations.<br><br>RESULTS: At Tn, all subjects exhibited improved VA for both far and near distances compared to values detected at T0. Similarly, VEP amplitude and latency values at Tn showed a greater P100 improvement than those observed at T0. Additionally, the CS examination at Tn demonstrated improvement, particularly at high spatial stimulation frequencies. The Tn SD-OCT results highlighted a reduction in macular thickness compared to T0 values.<br><br>CONCLUSIONS: This exploratory research indicates that intravitreal injections of AFL, following a fixed-dosing regimen, represent a valuable therapeutic approach for enhancing visual performance. This conclusion is supported by comprehensive statistical analysis of psychophysical, electro-functional, and morphological examinations within the same group of patients with nAMD, as demonstrated for the first time.},
}
@article {pmid38725662,
year = {2024},
author = {Sun, GF and Qu, XH and Jiang, LP and Chen, ZP and Wang, T and Han, XJ},
title = {The mechanisms of natural products for eye disorders by targeting mitochondrial dysfunction.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1270073},
pmid = {38725662},
issn = {1663-9812},
abstract = {The human eye is susceptible to various disorders that affect its structure or function, including glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction has been identified as a critical factor in the pathogenesis and progression of eye disorders, making it a potential therapeutic target in the clinic. Natural products have been used in traditional medicine for centuries and continue to play a significant role in modern drug development and clinical therapeutics. Recently, there has been a surge in research exploring the efficacy of natural products in treating eye disorders and their underlying physiological mechanisms. This review aims to discuss the involvement of mitochondrial dysfunction in eye disorders and summarize the recent advances in the application of natural products targeting mitochondria. In addition, we describe the future perspective and challenges in the development of mitochondria-targeting natural products.},
}
@article {pmid38725183,
year = {2025},
author = {Lisker-Cervantes, A and Gill, Z and Gnanaraj, R and Rajeswaren, V and Mehta, N and Gange, B and Patnaik, JL and Lynch, AM and Palestine, AG and Mathias, M and Manoharan, N and Mandava, N and de Carlo Forest, TE},
title = {Differences in imaging biomarkers between patients with intermediate and advanced non-neovascular age-related macular degeneration (AMD) in the University of Colorado AMD registry.},
journal = {European journal of ophthalmology},
volume = {35},
number = {1},
pages = {276-282},
pmid = {38725183},
issn = {1724-6016},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; Aged ; *Tomography, Optical Coherence/methods ; *Choroid/pathology/diagnostic imaging ; *Fluorescein Angiography/methods ; *Biomarkers ; *Registries ; *Retinal Drusen/diagnosis ; Aged, 80 and over ; Geographic Atrophy/diagnosis ; Middle Aged ; Visual Acuity/physiology ; Wet Macular Degeneration/diagnosis/drug therapy ; Retrospective Studies ; },
abstract = {PURPOSE: To quantify and compare the different prevalence rates of specific retinal imaging biomarkers in patients with intermediate AMD (iAMD) and advanced non-neovascular AMD (nnAMD).<br><br>METHODS: Cross-sectional study of patients with iAMD and advanced nnAMD. Imaging studies were reviewed for qualitative imaging biomarkers. Choroidal thickness measurements were obtained subfoveally and in 1000&#x2005;um and 2000&#x2005;um intervals away from the fovea. The Chi-squared test and Fisher's exact test were used to compare rates of imaging biomarkers among the two cohorts. P-value of <0.05 was considered significant.<br><br>RESULTS: 376 eyes of 197 patients with iAMD and 187 eyes of 97 patients with advanced nnAMD were recruited. There were significantly lower rates of the following imaging biomarkers in the iAMD compared with the advanced nnAMD cohorts: soft drusen (66.0% vs. 84.2%, p&#x2009;=&#x2009;0.001), calcified drusen (4.3% vs. 40.0%, p&#x2009;<&#x2009;0.0001), RPD (26.2% vs. 53.3%, p&#x2009;<&#x2009;0.0001), ORT (0.5% vs. 46.9%, p&#x2009;<&#x2009;0.0001), RP (1.1% vs. 46.3%, p&#x2009;<&#x2009;0.0001), pigment migration (53.2% vs. 100%, p&#x2009;<&#x2009;0.0001), and iRORA (17.9% vs. 80.2%, p&#x2009;<&#x2009;0.0001). In the iAMD cohort, choroidal thickness was significantly greater at 188&#x2005;&#xb5;m (SD: 60) and 194&#x2005;&#xb5;m (SD: 69), compared to the advanced nnAMD with measurements of 153&#x2005;&#xb5;m (SD: 68), and 161&#x2005;&#xb5;m (SD: 76). This difference was statistically significant (p&#x2009;<&#x2009;0.0001 and p&#x2009;=&#x2009;0.0002).<br><br>CONCLUSIONS: Our results highlight significant differences in imaging biomarkers between both cohorts. Key biomarkers, such as iRORA, RPD, pigment migration, and thinner choroidal thickness, were associated with advanced nnAMD. Identifying these biomarkers early may help target patients who could benefit from new treatments, potentially delaying vision loss.},
}
@article {pmid38725013,
year = {2024},
author = {Sun, Y and Hao, M and Wu, H and Zhang, C and Wei, D and Li, S and Song, Z and Tao, Y},
title = {Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies.},
journal = {Cell &amp; bioscience},
volume = {14},
number = {1},
pages = {59},
pmid = {38725013},
issn = {2045-3701},
support = {YXKC2021027//Health Science and Technology Innovation Outstanding Young Talents Training Program of Henan Province/ ; 20JCZD001//Basic Research Project of Henan Eye Institute/ ; 21JCZD002//Basic Research Project of Henan Eye Institute/ ; 221100310200//Science and Technology Major Project of Henan Province/ ; 224200510013//Central Plains Science and Technology Leading Talent Fund/ ; },
abstract = {Ca[2+]/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca[2+]-dependent signaling pathways. Its significance as an intracellular Ca[2+] sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.},
}
@article {pmid38723753,
year = {2024},
author = {Kumbhar, P and Kolekar, K and Vishwas, S and Shetti, P and Kumbar, V and Andreoli Pinto, TJ and Paiva-Santos, AC and Veiga, F and Gupta, G and Singh, SK and Dua, K and Disouza, J and Patravale, V},
title = {Treatment avenues for age-related macular degeneration: Breakthroughs and bottlenecks.},
journal = {Ageing research reviews},
volume = {98},
number = {},
pages = {102322},
doi = {10.1016/j.arr.2024.102322},
pmid = {38723753},
issn = {1872-9649},
mesh = {Humans ; *Macular Degeneration/therapy ; *Genetic Therapy/methods/trends ; Drug Delivery Systems/methods/trends ; Animals ; Nanoparticles/therapeutic use ; Stem Cell Transplantation/methods/trends ; },
abstract = {Age-related macular degeneration (AMD) is a significant factor contributing to serious vision loss in adults above 50. The presence of posterior segment barriers serves as chief roadblocks in the delivery of drugs to treat AMD. The conventional treatment strategies use is limited due to its off-targeted distribution in the eye, shorter drug residence, poor penetration and bioavailability, fatal side effects, etc. The above-mentioned downside necessitates drug delivery using some cutting-edge technology including diverse nanoparticulate systems and microneedles (MNs) which provide the best therapeutic delivery alternative to treat AMD efficiently. Furthermore, cutting-edge treatment modalities including gene therapy and stem cell therapy can control AMD effectively by reducing the boundaries of conventional therapies with a single dose. This review discusses AMD overview, conventional therapies for AMD and their restrictions, repurposed therapeutics and their anti-AMD activity through different mechanisms, and diverse barriers in drug delivery for AMD. Various nanoparticulate-based approaches including polymeric NPs, lipidic NPs, exosomes, active targeted NPs, stimuli-sensitive NPs, cell membrane-coated NPs, inorganic NPs, and MNs are explained. Gene therapy, stem cell therapy, and therapies in clinical trials to treat AMD are also discussed. Further, bottlenecks of cutting-edge (nanoparticulate) technology-based drug delivery are briefed. In a nutshell, cutting-edge technology-based therapies can be an effective way to treat AMD.},
}
@article {pmid38723422,
year = {2024},
author = {Chucair-Elliott, AJ and Ocañas, SR and Pham, K and Machalinski, A and Plafker, S and Stout, MB and Elliott, MH and Freeman, WM},
title = {Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium.},
journal = {Neurobiology of aging},
volume = {140},
number = {},
pages = {41-59},
pmid = {38723422},
issn = {1558-1497},
support = {P30 EY021725/EY/NEI NIH HHS/United States ; I01 BX005592/BX/BLRD VA/United States ; R01 EY034946/EY/NEI NIH HHS/United States ; IK6 BX006033/BX/BLRD VA/United States ; R01 EY019494/EY/NEI NIH HHS/United States ; T32 AG052363/AG/NIA NIH HHS/United States ; P30 AG050911/AG/NIA NIH HHS/United States ; R01 AG059430/AG/NIA NIH HHS/United States ; F31 AG064861/AG/NIA NIH HHS/United States ; I01 BX003906/BX/BLRD VA/United States ; },
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/pathology ; Female ; Male ; *Aging/genetics/physiology/pathology ; *Macular Degeneration/genetics/pathology/etiology ; *Sex Characteristics ; Transcriptome ; Disease Models, Animal ; Gene Expression ; Inflammation ; Mice ; Mice, Inbred C57BL ; },
abstract = {Aging is the main risk factor for age-related macular degeneration (AMD), a retinal neurodegenerative disease that leads to irreversible blindness, particularly in people over 60 years old. Retinal pigmented epithelium (RPE) atrophy is an AMD hallmark. Genome-wide chromatin accessibility, DNA methylation, and gene expression studies of AMD and control RPE demonstrate epigenomic/transcriptomic changes occur during AMD onset and progression. However, mechanisms by which molecular alterations of normal aging impair RPE function and contribute to AMD pathogenesis are unclear. Here, we specifically interrogate the RPE translatome with advanced age and across sexes in a novel RPE reporter mouse model. We find differential age- and sex- associated transcript expression with overrepresentation of pathways related to inflammation in the RPE. Concordant with impaired RPE function, the phenotypic changes in the aged translatome suggest that aged RPE becomes immunologically active, in both males and females, with some sex-specific signatures, which supports the need for sex representation for in vivo studies.},
}
@article {pmid38722789,
year = {2024},
author = {Xu, T and Ye, J and Gan, L and Deng, S and Guo, Y and Tang, Y},
title = {Advancing Neurological Health: Insights into Aging, Immunity, and Vascular Dynamics.},
journal = {Aging and disease},
volume = {15},
number = {3},
pages = {939-944},
pmid = {38722789},
issn = {2152-5250},
mesh = {Humans ; *Aging/immunology/physiology ; Nervous System Diseases/immunology/physiopathology ; Neuroinflammatory Diseases/immunology/physiopathology ; },
abstract = {This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.},
}
@article {pmid38722644,
year = {2024},
author = {Fu, DJ and Bagga, P and Naik, G and Glinton, S and Faes, L and Liefers, B and Lima, R and Wignall, G and Keane, PA and Ioannidou, E and Ribeiro Reis, AP and McKeown, A and Scheibler, L and Patel, PJ and Moghul, I and Pontikos, N and Balaskas, K},
title = {Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months.},
journal = {JAMA ophthalmology},
volume = {142},
number = {6},
pages = {548-558},
pmid = {38722644},
issn = {2168-6173},
mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy ; *Tomography, Optical Coherence ; Female ; *Intravitreal Injections ; Male ; Aged ; Double-Blind Method ; *Visual Acuity/physiology ; *Fluorescein Angiography/methods ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Consensus ; Treatment Outcome ; Follow-Up Studies ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; },
abstract = {IMPORTANCE: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials.<br><br>OBJECTIVE: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points.<br><br>This was a post hoc analysis of 11&#x202f;614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion &#x2265;1.25 mm2). This analysis was conducted from September to December 2023.<br><br>INTERVENTIONS: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal).<br><br>RESULTS: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P&#x2009;<&#x2009;.001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P&#x2009;<&#x2009;.001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P&#x2009;=&#x2009;.17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month.<br><br>CONCLUSIONS AND RELEVANCE: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.},
}
@article {pmid38722314,
year = {2024},
author = {Nakai-Futatsugi, Y and Jin, J and Ogawa, T and Sakai, N and Maeda, A and Hironaka, KI and Fukuda, M and Danno, H and Tanaka, Y and Hori, S and Shiroguchi, K and Takahashi, M},
title = {Pigmentation level of human iPSC-derived RPE does not indicate a specific gene expression profile.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {38722314},
issn = {2050-084X},
support = {18H05411//Japan Society for the Promotion of Science/ ; Special Postdoctoral Researchers Program of RIKEN//RIKEN/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology/physiology ; *Induced Pluripotent Stem Cells/metabolism ; *Pigmentation/genetics ; *Transcriptome ; Gene Expression Profiling ; Cells, Cultured ; Cell Differentiation/genetics ; },
abstract = {Retinal pigment epithelium (RPE) cells show heterogeneous levels of pigmentation when cultured in vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single-cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized into four clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.},
}
@article {pmid38721500,
year = {2024},
author = {Muto, T and Machida, S and Imaizumi, S},
title = {Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes.},
journal = {International journal of ophthalmology},
volume = {17},
number = {3},
pages = {545-550},
pmid = {38721500},
issn = {2222-3959},
abstract = {AIM: To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections (IVAIs) on immediate intraocular pressure (IOP) increase and vitreous reflux (VR) rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.<br><br>METHODS: This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion, 35 patients with diabetic macular edema, 69 patients with neovascular age-related macular degeneration (nAMD), and 12 patients with myopic choroidal neovascularization, which underwent first-time IVAI. The correlation of immediate IOP increase and VR rates with the four background diseases was investigated. Moreover, the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated. Further, 54 patients with nAMD were treated with IVAI>10 times (multiple IVAIs). Moreover, the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.<br><br>RESULTS: The immediate IOP increase (P=0.16) and VR rates (P=0.50) were almost similar among the four background diseases. The immediate postinjection IOP and age, VR rate and age, immediate postinjection IOP and axial length, or VR rate and axial length were not correlated in the four background diseases. The immediate IOP increase (P=0.66) and VR rates (P=0.28) did not significantly differ between first-time and multiple IVAIs in nAMD.<br><br>CONCLUSION: Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate. Further, age and axial length have no correlation on immediate IOP increase and VR rate.},
}
@article {pmid38721051,
year = {2024},
author = {Lyu, A and Silva, AE and Thompson, B and Abel, L and Cheong, AMY},
title = {Visual cortex anodal transcranial direct current stimulation does not alter reading performance for Chinese presented character-by-character to normal peripheral vision in older adults.},
journal = {Frontiers in neuroscience},
volume = {18},
number = {},
pages = {1341307},
pmid = {38721051},
issn = {1662-4548},
abstract = {Visual cortex anodal transcranial direct current stimulation (a-tDCS) has been shown to reduce crowding in normal peripheral vision and may improve the reading of English words in patients with macular degeneration. Given the different visual requirements of reading English words and Chinese characters, the effect of a-tDCS on peripheral reading performance in English might differ from Chinese. This study recruited 20 participants (59-73 years of age) with normal vision and tested the hypothesis that a-tDCS would improve the reading of Chinese characters presented at 10° eccentricity compared with sham stimulation. Chinese sentences of different print sizes and exposure durations were presented one character at a time, 10° below or to the left of fixation. The individual critical print size (CPS) - the smallest print size eliciting the maximum reading speed (MRS) - was determined. Reading accuracies for characters presented 0.2 logMAR smaller than the individually fitted CPS were measured at four time points: before, during, 5 min after, and 30 min after receiving active or sham visual cortex a-tDCS. Participants completed both the active and sham sessions in a random order following a double-blind, within-subject design. No effect of active a-tDCS on reading accuracy was observed, implying that a single session of a-tDCS did not improve Chinese character reading in normal peripheral vision. This may suggest that a-tDCS does not significantly reduce the crowding elicited within a single Chinese character. However, the effect of a-tDCS on between-character crowding is yet to be determined.},
}
@article {pmid38720929,
year = {2024},
author = {Nguyen, VP and Hu, J and Zhe, J and Ramasamy, S and Ahmed, U and Paulus, YM},
title = {Advanced nanomaterials for imaging of eye diseases.},
journal = {ADMET &amp; DMPK},
volume = {12},
number = {2},
pages = {269-298},
pmid = {38720929},
issn = {1848-7718},
support = {R01 EY033000/EY/NEI NIH HHS/United States ; R01 EY034325/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND AND PURPOSE: Vision impairment and blindness present significant global challenges, with common causes including age-related macular degeneration, diabetes, retinitis pigmentosa, and glaucoma. Advanced imaging tools, such as optical coherence tomography, fundus photography, photoacoustic microscopy, and fluorescence imaging, play a crucial role in improving therapeutic interventions and diagnostic methods. Contrast agents are often employed with these tools to enhance image clarity and signal detection. This review aims to explore the commonly used contrast agents in ocular disease imaging.<br><br>EXPERIMENTAL APPROACH: The first section of the review delves into advanced ophthalmic imaging techniques, outlining their importance in addressing vision-related issues. The emphasis is on the efficacy of therapeutic interventions and diagnostic methods, establishing a foundation for the subsequent exploration of contrast agents.<br><br>KEY RESULTS: This review focuses on the role of contrast agents, with a specific emphasis on gold nanoparticles, particularly gold nanorods. The discussion highlights how these contrast agents optimize imaging in ocular disease diagnosis and monitoring, emphasizing their unique properties that enhance signal detection and imaging precision.<br><br>CONCLUSION: The final section, we explores both organic and inorganic contrast agents and their applications in specific conditions such as choroidal neovascularization, retinal neovascularization, and stem cell tracking. The review concludes by addressing the limitations of current contrast agent usage and discussing potential future clinical applications. This comprehensive exploration contributes to advancing our understanding of contrast agents in ocular disease imaging and sets the stage for further research and development in the field.},
}
@article {pmid38719453,
year = {2024},
author = {Carleton, M and Oesch, NW},
title = {Asymmetric Activation of ON and OFF Pathways in the Degenerated Retina.},
journal = {eNeuro},
volume = {11},
number = {5},
pages = {},
pmid = {38719453},
issn = {2373-2822},
support = {R01 EY029259/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Retinal Ganglion Cells/physiology ; *Electric Stimulation ; Retinal Degeneration/physiopathology ; Mice, Inbred C57BL ; Retinal Bipolar Cells/physiology ; Patch-Clamp Techniques ; Visual Pathways/physiology/physiopathology ; Neural Inhibition/physiology ; Female ; Male ; Retina/physiology ; Amacrine Cells/physiology ; },
abstract = {Retinal prosthetics are one of the leading therapeutic strategies to restore lost vision in patients with retinitis pigmentosa and age-related macular degeneration. Much work has described patterns of spiking in retinal ganglion cells (RGCs) in response to electrical stimulation, but less work has examined the underlying retinal circuitry that is activated by electrical stimulation to drive these responses. Surprisingly, little is known about the role of inhibition in generating electrical responses or how inhibition might be altered during degeneration. Using whole-cell voltage-clamp recordings during subretinal electrical stimulation in the rd10 and wild-type (wt) retina, we found electrically evoked synaptic inputs differed between ON and OFF RGC populations, with ON cells receiving mostly excitation and OFF cells receiving mostly inhibition and very little excitation. We found that the inhibition of OFF bipolar cells limits excitation in OFF RGCs, and a majority of both pre- and postsynaptic inhibition in the OFF pathway arises from glycinergic amacrine cells, and the stimulation of the ON pathway contributes to inhibitory inputs to the RGC. We also show that this presynaptic inhibition in the OFF pathway is greater in the rd10 retina, compared with that in the wt retina.},
}
@article {pmid38719131,
year = {2024},
author = {Ehlers, JP and McConville, C and Yordi, S and Cetin, H and Cakir, Y and Kalra, G and Amine, R and Whitney, J and Whitmore, V and Bonnay, M and Reese, J and Clark, J and Zhu, L and Luo, D and Jaffe, GJ and Srivastava, SK},
title = {Correlation Between Blue Fundus Autofluorescence and SD-OCT Measurements of Geographic Atrophy in Dry Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {266},
number = {},
pages = {92-101},
doi = {10.1016/j.ajo.2024.04.031},
pmid = {38719131},
issn = {1879-1891},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/diagnosis ; Prospective Studies ; *Fluorescein Angiography/methods ; Double-Blind Method ; *Fundus Oculi ; Female ; Reproducibility of Results ; Male ; Aged ; Visual Acuity/physiology ; Intravitreal Injections ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Angiogenesis Inhibitors/therapeutic use ; Optical Imaging ; },
abstract = {PURPOSE: To compare fundus autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) measurements of geographic atrophy (GA) area and to analyze lesion area changes measured by spectral domain OCT in GATHER1.<br><br>DESIGN: An assessment reliability analysis using prospective, randomized, double-masked phase 2/3 clinical trial data.<br><br>METHODS: GATHER1 examined the efficacy and safety of avacincaptad pegol (ACP) for GA treatment. A post hoc analysis was performed to identify correlations between FAF- and OCT-based measurements of GA. GA area was measured on blue-light FAF images using semiautomatic segmentation software with support from OCT and near-infrared imaging. Machine-learning enhanced, multilayer segmentation of OCT scans were reviewed by human readers, and segmentation errors were corrected as needed. GA area was defined as total RPE loss on cross-sectional B scans. Time points included Months 0, 6, 12, and 18. Additionally, OCT-based GA-area changes between ACP and sham were analyzed.<br><br>RESULTS: There was a strong correlation (r = 0.93) between FAF and OCT GA area measurements that persisted through 18 months. Mean (SD) differences between OCT and FAF GA measurements were negligible: 0.11 mm[2] (1.42) at Month 0, 0.03 mm[2] (1.62) at Month 6, -0.17 mm[2] (1.81) at Month 12, and -0.07 mm[2] (1.78) at Month 18. OCT assessments of GA growth revealed a 30% and 27% reduction at Months 12 and 18, respectively, between ACP and sham, replicating FAF measurements from GATHER1.<br><br>CONCLUSIONS: The strong correlation between blue FAF and OCT measurements of GA area supports OCT as a reliable method to measure GA lesion area in clinical trials.},
}
@article {pmid38718102,
year = {2025},
author = {Hamedani, AG and Willis, AW and Ying, GS},
title = {Self-reported Visual Difficulty, Age-related Eye Disease, and Neuropsychiatric Outcomes in Older Adults.},
journal = {Ophthalmic epidemiology},
volume = {32},
number = {1},
pages = {103-111},
pmid = {38718102},
issn = {1744-5086},
support = {K23 EY033438/EY/NEI NIH HHS/United States ; K24 AG075234/AG/NIA NIH HHS/United States ; U01 AG032947/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Aged ; Male ; Female ; Retrospective Studies ; *Self Report ; Aged, 80 and over ; *Vision Disorders/epidemiology ; United States/epidemiology ; *Cataract/epidemiology ; *Macular Degeneration/epidemiology ; *Diabetic Retinopathy/epidemiology ; *Glaucoma, Open-Angle/epidemiology ; *Dementia/epidemiology ; Visual Acuity ; Incidence ; },
abstract = {PURPOSE: Self-reported visual difficulty is consistently associated with dementia and other neuropsychiatric outcomes, but studies of specific age-related eye diseases have yielded conflicting results.<br><br>METHODS: We conducted a retrospective cohort study using data from The National Health and Aging Trends Study, an ongoing nationally representative survey of older U.S. adults (n&#x2009;=&#x2009;10,089). All subjects are screened for self-reported visual difficulty annually. Using linked Medicare claims data, we identified subjects with age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), diabetic retinopathy, and cataract. For each condition, controls with complete Medicare eligibility and at least one eye care encounter were selected. We used semiparametric discrete time proportional hazards models to measure associations with incident dementia, and generalized estimating equations to examine longitudinal associations with depression, anxiety, and hallucinations, adjusting for baseline demographics and time-varying comorbidities.<br><br>RESULTS: Self-reported visual difficulty was associated with dementia (HR 1.16, 95% CI: 1.00-1.34), depression (OR 1.14, 95% CI: 1.04-1.26), anxiety (OR 1.17, 95% CI: 1.06-1.29), and hallucinations (OR 1.54, 95% CI: 1.29-1.84). Diabetic retinopathy was associated with depression (OR 1.31, 95% CI: 1.05-1.64), and cataracts were associated with a lower risk of depression (OR 0.84, 95% CI: 0.74-0.95) and anxiety (OR 0.86, 95% CI: 0.75-0.99). There were no other associations between age-related eye disease and neuropsychiatric outcomes.<br><br>CONCLUSION: Self-reported visual difficulty is associated with dementia and other neuropsychiatric outcomes to a greater degree than age-related eye disease. These findings highlight the distinction between self-reported vision and clinically diagnosed eye disease with regard to health outcomes in older adults.},
}
@article {pmid38717425,
year = {2024},
author = {Owsley, C and McGwin, G and Swain, TA and Clark, ME and Thomas, TN and Goerdt, L and Sloan, KR and Trittschuh, EH and Jiang, Y and Owen, JP and Lee, CS and Curcio, CA},
title = {Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {5},
pages = {16},
pmid = {38717425},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Aged ; Female ; Cross-Sectional Studies ; *Aging/physiology ; Aged, 80 and over ; *Macular Degeneration/physiopathology ; *Cognition/physiology ; *Retina/diagnostic imaging/pathology/physiopathology ; Nerve Fibers/pathology ; Retinal Ganglion Cells/pathology ; },
abstract = {PURPOSE: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD.<br><br>METHODS: Adults &#x2265; 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age.<br><br>RESULTS: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition.<br><br>CONCLUSIONS: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.},
}
@article {pmid38717424,
year = {2024},
author = {Emamverdi, M and Vatanatham, C and Fasih-Ahmad, S and Wang, Z and Mishra, Z and Jain, A and Ganegoda, A and Clark, ME and Habibi, A and Ashrafkhorasani, M and Owsley, C and Curcio, CA and Hu, ZJ and Sadda, SR},
title = {Probing Deposit-Driven Age-Related Macular Degeneration Via Thicknesses of Outer Retinal Bands and Choroid: ALSTAR2 Baseline.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {5},
pages = {17},
pmid = {38717424},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Choroid/pathology/diagnostic imaging ; Cross-Sectional Studies ; *Macular Degeneration/diagnosis ; *Retinal Drusen/diagnosis ; Retinal Photoreceptor Cell Outer Segment/pathology ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Visual Acuity/physiology ; },
abstract = {PURPOSE: We aimed to identify structural differences in normal eyes, early age-related macular degeneration (AMD), and intermediate AMD eyes using optical coherence tomography (OCT) in a well-characterized, large cross-sectional cohort.<br><br>METHODS: Subjects &#x2265; 60&#xa0;years with healthy normal eyes, as well as early or intermediate AMD were enrolled in the Alabama Study on Age-related Macular Degeneration 2 (ALSTAR2; NCT04112667). Using Spectralis HRA + OCT2, we obtained macular volumes for each participant. An auto-segmentation software was used to segment six layers and sublayers: photoreceptor inner and outer segments, subretinal drusenoid deposits (SDDs), retinal pigment epithelium + basal lamina (RPE + BL), drusen, and choroid. After manually refining the segmentations of all B-scans, mean thicknesses in whole, central, inner and outer rings of the ETDRS grid were calculated and compared among groups.<br><br>RESULTS: This study involved 502 patients, 252 were healthy, 147 had early AMD, and 103 had intermediate AMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step). Intermediate AMD eyes exhibited thicker SDD and drusen, thinner photoreceptor inner segments, and RPE compared to healthy and early AMD eyes. They also had thicker photoreceptor outer segments than early AMD eyes. Early AMD eyes had thinner photoreceptor outer segments than normal eyes but a thicker choroid than intermediate AMD eyes. Using the Beckman scale, 42% of the eyes initially classified as early AMD shifted to intermediate AMD, making thickness differences for photoreceptor outer segments and choroid insignificant.<br><br>CONCLUSIONS: With AMD stages, the most consistent structural differences involve appearance of drusen and SDD, followed by RPE + BL thickness, and then thickness of photoreceptor inner and outer segments. Structural changes in the transition from aging to intermediate AMD include alterations in the outer retinal bands, including the appearance of deposits on either side of the RPE.},
}
@article {pmid38713397,
year = {2024},
author = {Shiose, S and Notomi, S and Hashimoto, S and Nagata, J and Fukuda, Y and Kano, K and Ishikawa, K and Sonoda, KH},
title = {The factors associated with retinal pigment epithelium tear development in the early phase after treatment initiation for age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {10},
pages = {3171-3180},
pmid = {38713397},
issn = {1435-702X},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Retinal Perforations/diagnosis/etiology ; Aged ; *Retinal Pigment Epithelium/pathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Intravitreal Injections ; *Fundus Oculi ; *Visual Acuity ; Follow-Up Studies ; Ranibizumab/administration &amp; dosage ; Risk Factors ; Time Factors ; Aged, 80 and over ; },
abstract = {PURPOSE: This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED).<br><br>METHODS: Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3&#xa0;months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3&#xa0;months of starting anti-VEGF therapy was examined.<br><br>RESULTS: This study included 244 eyes (230 patients; mean age 75.0&#xa0;years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3&#xa0;months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100&#xa0;&#xb5;m, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07-2.12, p&#x2009;=&#x2009;0.019), PED area (every 10 mm[2], OR: 3.02, CI: 1.22-7.46, p&#x2009;=&#x2009;0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12-850.59, p&#x2009;=&#x2009;0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p&#x2009;=&#x2009;0.01, &#x3c7;-square test).<br><br>CONCLUSIONS: Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs.},
}
@article {pmid38712900,
year = {2024},
author = {Boulakh, L and Isaksen, JL and Poulsen, HE and Faber, J and Heegaard, S and Nygaard, B and Kanters, JK and Toft, PB and Mortens Udholm, P and Bek, T and Buch Hesgaard, H and Ellervik, C},
title = {Thyroid dysfunction and exudative age-related macular degeneration - A longitudinal nationwide registry-based cohort study.},
journal = {Acta ophthalmologica},
volume = {102},
number = {7},
pages = {813-820},
doi = {10.1111/aos.16705},
pmid = {38712900},
issn = {1755-3768},
support = {//Mikael Bondum (private donor)/ ; 20-B-0454-Helsefonden//Helsefonden/ ; //Synoptik-Fonden/ ; 21-5-0289//Ole Kirk's Fond/ ; PD2Y-2023004-DCA//Danish Cardiovascular Academy/ ; //Novo Nordisk Foundation/ ; NNF20SA0067242//Danish Heart Foundation/ ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Denmark/epidemiology ; Follow-Up Studies ; *Hyperthyroidism/complications/diagnosis/epidemiology ; *Hypothyroidism/epidemiology/diagnosis/complications ; Incidence ; Registries ; Retrospective Studies ; Risk Factors ; *Wet Macular Degeneration/diagnosis/epidemiology/physiopathology ; },
abstract = {PURPOSE: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown.<br><br>METHODS: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group.<br><br>RESULTS: We included 2&#x2009;087&#x2009;305 individuals, of which 1&#x2009;072&#x2009;567 (51.4%) were women; 59&#x2009;318 (2.8%) had hypothyroidism, and 33&#x2009;922 (1.6%) had hyperthyroidism. During a median follow-up of 11&#x2009;years, 26&#x2009;998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p&#x2009;<&#x2009;0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p&#x2009;<&#x2009;0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population.<br><br>CONCLUSION: This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association.},
}
@article {pmid38711521,
year = {2024},
author = {Song, Y and Liao, Y and Liu, T and Chen, Y and Wang, F and Zhou, Z and Zhang, W and Li, J},
title = {Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1366841},
pmid = {38711521},
issn = {1664-3224},
mesh = {Animals ; *Choroidal Neovascularization/etiology/drug therapy/metabolism/pathology ; *Microglia/metabolism/drug effects ; Mice ; *Disease Models, Animal ; *Aminopyridines/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Macular Degeneration/pathology/metabolism/drug therapy ; Inflammation ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists &amp; inhibitors/metabolism ; Pyrroles/pharmacology/therapeutic use ; Cellular Senescence/drug effects ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD.<br><br>METHODS: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-&#x3b2;-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed.<br><br>RESULTS: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions.<br><br>DISCUSSION: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.},
}
@article {pmid38710939,
year = {2024},
author = {Thottarath, S and Gurudas, S and Chandak, S and Patel, PJ and Kotagiri, A and Pearce, I and McKibbin, M and Menon, G and Burton, BJL and Talks, J and Grabowska, A and Ghanchi, F and Gale, R and Karatsai, E and Chandra, S and Sivaprasad, S},
title = {Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5.},
journal = {Eye (London, England)},
volume = {38},
number = {14},
pages = {2737-2743},
pmid = {38710939},
issn = {1476-5454},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Intravitreal Injections ; *Visual Acuity/physiology ; Male ; Female ; *Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Treatment Outcome ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {OBJECTIVE: To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD).<br><br>METHODS: Patients with nAMD initiated on the loading phase of three intravitreal doses of 2&#x2009;mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated.<br><br>RESULTS: A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by &#x2265;5 letters and a&#x2009;>&#x2009;25&#x2009;&#x3bc;m increase in central sub-field thickness (CST)&#xa0;are considered, 90% will be eligible for interval extension.<br><br>CONCLUSION: Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown.},
}
@article {pmid38710714,
year = {2024},
author = {Luo, S and Jiang, H and Li, Q and Qin, Y and Yang, S and Li, J and Xu, L and Gou, Y and Zhang, Y and Liu, F and Ke, X and Zheng, Q and Sun, X},
title = {An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {3780},
pmid = {38710714},
issn = {2041-1723},
mesh = {Animals ; *Dependovirus/genetics ; *Genetic Vectors/genetics/administration &amp; dosage ; *Genetic Therapy/methods ; Mice ; *Retinal Pigment Epithelium/metabolism/virology ; *Choroidal Neovascularization/therapy/genetics ; Rabbits ; Humans ; Gene Transfer Techniques ; Macular Degeneration/therapy/genetics/pathology ; Disease Models, Animal ; Capsid Proteins/genetics/metabolism ; Transduction, Genetic ; Vascular Endothelial Growth Factor A/genetics/metabolism ; Mice, Inbred C57BL ; Retina/metabolism/virology ; Male ; HEK293 Cells ; },
abstract = {Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.},
}
@article {pmid38710357,
year = {2024},
author = {Tahmasebi Sarvestani, M and Chidlow, G and Wood, JP and Casson, RJ},
title = {Effects of slit lamp-delivered retinal laser photobiomodulation in a rat model of choroidal neovascularization.},
journal = {Experimental eye research},
volume = {244},
number = {},
pages = {109909},
doi = {10.1016/j.exer.2024.109909},
pmid = {38710357},
issn = {1096-0007},
mesh = {Animals ; Rats ; *Disease Models, Animal ; *Rats, Inbred BN ; *Choroidal Neovascularization/metabolism/pathology/etiology ; *Fluorescein Angiography ; *Tomography, Optical Coherence ; *Laser Coagulation/methods ; *Low-Level Light Therapy/methods ; *Vascular Endothelial Growth Factor A/metabolism ; Enzyme-Linked Immunosorbent Assay ; Male ; Slit Lamp Microscopy ; Immunohistochemistry ; },
abstract = {Neovascular age-related macular degeneration, also known as exudative or wet age-related macular degeneration, is the leading cause of blindness in the developed world. Photobiomodulation has the potential to target the up-stream hypoxic and pro-inflammatory drivers of choroidal neovascularization. This study investigated whether photobiomodulation attenuates characteristic pathological features of choroidal neovascularization in a rodent model. Experimental choroidal neovascularization was induced in Brown Norway rats with laser photocoagulation. A custom-designed, slit-lamp-mounted, 670 nm laser was used to administer retinal photobiomodulation every 3 days, beginning 6 days prior to choroidal neovascularization induction and continuing until the animals were killed 14 days later. The effect of photobiomodulation on the size of choroidal neovascular membranes was determined using isolectin-B4 immunohistochemistry and spectral domain-optical coherence tomography. Vascular leakage was determined with fluorescein angiography. The effect of treatment on levels of vascular endothelial growth factor expression was quantified with enzyme-linked immunosorbent assay. Treatment with photobiomodulation was associated with choroidal neovascular membranes that were smaller, had less fluorescein leakage, and a diminished presence of inflammatory cells as compared to sham eyes. These effects were not associated with a statistically significant difference in the level of vascular endothelial growth factor when compared to sham eyes. The data shown herein indicate that photobiomodulation attenuates pathological features of choroidal neovascularization in a rodent model by mechanisms that may be independent of vascular endothelial growth factor.},
}
@article {pmid38709525,
year = {2024},
author = {Cicinelli, MV and Barlocci, E and Giuffrè, C and Rissotto, F and Introini, U and Bandello, F},
title = {Integrating Machine Learning and Traditional Survival Analysis to Identify Key Predictors of Foveal Involvement in Geographic Atrophy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {5},
pages = {10},
pmid = {38709525},
issn = {1552-5783},
mesh = {Humans ; *Fovea Centralis/pathology/diagnostic imaging ; Male ; Female ; *Geographic Atrophy/diagnosis ; Aged ; Retrospective Studies ; *Machine Learning ; *Tomography, Optical Coherence/methods ; Risk Factors ; Aged, 80 and over ; Visual Acuity/physiology ; Follow-Up Studies ; Fluorescein Angiography/methods ; Incidence ; Middle Aged ; Survival Analysis ; },
abstract = {PURPOSE: The purpose of this study was to investigate the incidence of foveal involvement in geographic atrophy (GA) secondary to age-related macular degeneration (AMD), using machine learning to assess the importance of risk factors.<br><br>METHODS: Retrospective, longitudinal cohort study. Patients diagnosed with foveal-sparing GA, having GA size &#x2265; 0.049&#xa0;mm&#xb2; and follow-up &#x2265; 6&#xa0;months, were included. Baseline GA area, distance from the fovea, and perilesional patterns were measured using fundus autofluorescence. Optical coherence tomography assessed foveal involvement, structural biomarkers, and outer retinal layers thickness. Onset of foveal involvement was recorded. Foveal survival rates were estimated using Kaplan-Meier curves. Hazard ratios (HRs) were assessed with mixed model Cox regression. Variable Importance (VIMP) was ranked with Random Survival Forests (RSF), with higher scores indicating greater predictive significance.<br><br>RESULTS: One hundred sixty-seven eyes (115 patients, average age = 75.8 &#xb1; 9.47&#xa0;years) with mean follow-up of 50 &#xb1; 29&#xa0;months, were included in this study. Median foveal survival time was 45&#xa0;months (95% confidence interval [CI] = 38-55). Incidences of foveal involvement were 26% at 24&#xa0;months and 67% at 60&#xa0;months. Risk factors were GA proximity to the fovea (HR = 0.97 per 10-&#xb5;m increase, 95% CI = 0.96-0.98), worse baseline visual acuity (HR = 1.37 per 0.1 LogMAR increase, 95% CI = 1.21-1.53), and thinner outer nuclear layer (HR = 0.59 per 10-&#xb5;m increase, 95% CI = 0.46-0.74). RSF analysis confirmed these as main predictors (VIMP = 16.7, P = 0.002; VIMP = 6.2, P = 0.003; and VIMP = 3.4, P = 0.01). Lesser baseline GA area (HR = 1.09 per 1-mm2 increase, 95% CI = 1.01-1.16) and presence of a double layer sign (HR = 0.42, 95% CI = 0.20-0.88) were protective but less influential.<br><br>CONCLUSIONS: This study identifies anatomic and functional factors impacting the risk of foveal involvement in GA. These findings may help identify at-risk patients, enabling tailored preventive strategies.},
}
@article {pmid38708561,
year = {2024},
author = {Novack, GD and Robin, AL},
title = {Ocular Pharmacology.},
journal = {Journal of clinical pharmacology},
volume = {64},
number = {9},
pages = {1068-1082},
doi = {10.1002/jcph.2451},
pmid = {38708561},
issn = {1552-4604},
mesh = {Humans ; *Eye Diseases/drug therapy ; *Ophthalmic Solutions/pharmacokinetics/administration &amp; dosage ; Eye/metabolism/drug effects ; Administration, Ophthalmic ; Pharmaceutical Preparations/administration &amp; dosage/metabolism ; Animals ; },
abstract = {Treatment of ocular diseases presents unique challenges and opportunities for the clinician and for the clinical pharmacologist. Ophthalmic pharmaceuticals, typically given as liquids, require consideration of solubility, physiological pH, and osmolarity, as well as sterility and stability, which in turn requires optimal pharmaceutics. Ocular tissue levels are challenging to obtain in humans, and the clinical pharmacokinetics is typically blood levels, which are primarily related to safety, rather than efficacy. The eye is a closed compartment with multiple physiological barriers with esterases and transporters, but relatively little cytochrome oxidases. Delivery routes include topical, intravitreal, and systemic. Patient dosing involves not only adherence issues common to all chronic diseases, but also performance requirements on eye drop instillation. Therapeutically, ocular diseases and their pharmacological treatments include both those analogous to systemic diseases (e.g., inflammation, infection, and neuronal degeneration) and those unique to the eye (e.g., cataract and myopia).},
}
@article {pmid38706458,
year = {2024},
author = {Yoon, B and Sa, HS and Kim, HJ},
title = {Incidence and risk factors of age-related macular degeneration in patients with Parkinson's disease: a population-based study.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1331786},
pmid = {38706458},
issn = {1663-4365},
abstract = {BACKGROUND AND OBJECTIVE: The association between age-related macular degeneration (AMD) and Parkinson' disease (PD) remains unclear. The aim of the present study was to assess the incidence of AMD in patients with PD, elucidate differences by age and sex, and investigate potential risk factors for AMD.<br><br>METHODS: Data were extracted from the Korean National Health Insurance System database, which covers 97% of the Korean population (2002 through 2019). We calculated the incidence of newly diagnosed AMD in patients with PD and used Cox proportional-hazards models to estimate risk factors for AMD, presenting adjusted hazard ratios (aHR) with 95% confidence intervals (CI).<br><br>RESULTS: Of 172,726 patients with PD, 15,800 were newly diagnosed with AMD during the follow-up, including 5,624 men and 10,176 women. The overall incidence of AMD in patients with PD was 13.59 per 1,000 person-years. Stratified by age group and sex, the incidence was higher in women aged 40-69, and conversely higher in men aged 70-89. Risk of AMD was high in older age groups (aHR = 4.36, 95% CI: 3.74-5.09 in the 70 s), female sex (aHR = 1.07, 95% CI: 1.04-1.11), patients with diabetes mellitus (DM) (aHR = 1.14, 95% CI: 1.10-1.18), and patients with hyperlipidemia (aHR = 1.17, 95% CI: 1.13-1.21).<br><br>CONCLUSION: Our findings suggest that the AMD incidence is higher in patients with PD than in the general population, with varying patterns of sex differences across age groups. Particularly, old age, female sex, presence of DM, and hyperlipidemia are potential risk factors. Therefore, clinicians should pay greater attention to AMD in patients with PD.},
}
@article {pmid38706195,
year = {2024},
author = {Kim, DJ and Kim, DG and Kwak, HD and Jang, JY and Ji, YS and Lee, SH and Lee, EK and Park, KH and Kim, JH and Lee, JS and Song, Y and Kim, ST and Shin, MH and Kim, M and Park, SJ and Joo, K and Sagong, M and Lee, CS and Woo, SJ},
title = {Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.},
journal = {Acta ophthalmologica},
volume = {102},
number = {7},
pages = {e1018-e1028},
doi = {10.1111/aos.16699},
pmid = {38706195},
issn = {1755-3768},
support = {RS-2023-00248480//Ministry of Science and ICT, South Korea/ ; },
mesh = {Humans ; Retrospective Studies ; Male ; *Intravitreal Injections ; Female ; Aged ; *Tomography, Optical Coherence/methods ; *Visual Acuity ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Fluorescein Angiography/methods ; Treatment Outcome ; *Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use/administration &amp; dosage ; Time Factors ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; },
abstract = {PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of &#x2265;12&#x2009;months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups.<br><br>RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1&#x2009;&#xb1;&#x2009;8.6&#x2009;years). 29 eyes (7.2%) were treatment na&#xef;ve. The mean follow-up period was 15.3&#x2009;&#xb1;&#x2009;2.8&#x2009;months; the mean number of BRZ injections within 1&#x2009;year was 4.5&#x2009;&#xb1;&#x2009;1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12&#x2009;months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1&#x2009;month and 42.9% at 12&#x2009;months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes)&#xa0;and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5&#x2009;&#xb1;&#x2009;1.4&#x2009;days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution.<br><br>CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1&#x2009;year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.},
}
@article {pmid38705908,
year = {2024},
author = {Kivrak, U and Arsan, AK and Akçay, G and Bulut, MN and Kanar, HS and Hacısalihoğlu, AO and Şimşek, &#x15e;},
title = {Clinical features, management, and outcomes of patients with sterile endophthalmitis associated with intravitreal bevacizumab injection: retrospective case series.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {216},
pmid = {38705908},
issn = {1573-2630},
mesh = {Humans ; *Bevacizumab/administration &amp; dosage/adverse effects ; *Intravitreal Injections ; *Endophthalmitis/diagnosis/etiology ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; Aged ; Middle Aged ; *Visual Acuity ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Macular Edema/drug therapy/diagnosis/etiology ; Retinal Vein Occlusion/diagnosis/drug therapy/complications ; Follow-Up Studies ; Diabetic Retinopathy/diagnosis/drug therapy ; },
abstract = {PURPOSE: To evaluate clinical features, treatment protocol, outcomes, and complications that developed in this case series of 24 patients who had consecutive sterile endophthalmitis after intravitreal bevacizumab (IVB) injection.<br><br>METHODS: In this retrospective case series, IVB was repackaged in individual aliquots from the three batches that were used on the same day. IVB was injected into 26 eyes of 26 patients due to diabetic macular edema, age-related macular degeneration, and branch retinal vein occlusion. All patients had intraocular inflammation. Patients were divided into two groups severe and moderate inflammation according to the intraocular inflammation. The medical records of all patients were reviewed. At each follow-up visit, the complete ophthalmologic examination was performed, including best corrected visual acuity (BCVA), intraocular pressure, biomicroscopy, and posterior fundus examination.<br><br>RESULTS: Twenty-four of 26 patients were included in the study. Two patients were excluded from this study since they didn't come to follow-up visits. The mean BCVA was 1.00 &#xb1; 0.52 Log MAR units before IVB. At the final visit, the BCVA was 1.04 &#xb1; 0.47 Log MAR units. These differences were not significant (p = 0.58). Of the 24 eyes, 16 eyes had severe, and 8 eyes had moderate intraocular inflammation. Eleven eyes in the severe inflammation group underwent pars plana vitrectomy due to intense vitreous opacity. Smear, culture results, and polymerase chain reaction results were negative.<br><br>CONCLUSION: Sterile endophthalmitis may occur after IVB injection. Differential diagnosis of sterile endophthalmitis from infective endophthalmitis is crucial to adjust the appropriate treatment and prevent long-term complications due to unnecessary treatment.},
}
@article {pmid38705321,
year = {2024},
author = {Yu, C and Xu, J and Heidari, G and Jiang, H and Shi, Y and Wu, A and Makvandi, P and Neisiany, RE and Zare, EN and Shao, M and Hu, L},
title = {Injectable hydrogels based on biopolymers for the treatment of ocular diseases.},
journal = {International journal of biological macromolecules},
volume = {269},
number = {Pt 1},
pages = {132086},
doi = {10.1016/j.ijbiomac.2024.132086},
pmid = {38705321},
issn = {1879-0003},
mesh = {*Hydrogels/chemistry ; Humans ; Biopolymers/chemistry ; *Eye Diseases/drug therapy ; Animals ; Drug Delivery Systems ; Injections ; Biocompatible Materials/chemistry ; },
abstract = {Injectable hydrogels based on biopolymers, fabricated utilizing diverse chemical and physical methodologies, exhibit exceptional physical, chemical, and biological properties. They have multifaceted applications encompassing wound healing, tissue regeneration, and across diverse scientific realms. This review critically evaluates their largely uncharted potential in ophthalmology, elucidating their diverse applications across an array of ocular diseases. These conditions include glaucoma, cataracts, corneal disorders (spanning from age-related degeneration to trauma, infections, and underlying chronic illnesses), retina-associated ailments (such as diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration (AMD)), eyelid abnormalities, and uveal melanoma (UM). This study provides a thorough analysis of applications of injectable hydrogels based on biopolymers across these ocular disorders. Injectable hydrogels based on biopolymers can be customized to have specific physical, chemical, and biological properties that make them suitable as drug delivery vehicles, tissue scaffolds, and sealants in the eye. For example, they can be engineered to have optimum viscosity to be injected intravitreally and sustain drug release to treat retinal diseases. Their porous structure and biocompatibility promote cellular infiltration to regenerate diseased corneal tissue. By accentuating their indispensable role in ocular disease treatment, this review strives to present innovative and targeted approaches in this domain, thereby advancing ocular therapeutics.},
}
@article {pmid38704812,
year = {2024},
author = {Willis, ET and Kim, JE and Schneider, EW},
title = {Home Optical Coherence Tomography Monitoring for Neovascular Age-Related Macular Degeneration: Transformative Technology or Cool Toy?.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {6},
pages = {1407-1416},
pmid = {38704812},
issn = {2193-8245},
abstract = {The pending introduction of home-based optical coherence tomography (OCT) in managing neovascular age-related macular degeneration (nAMD) has sparked interesting debates. Advocates assert that home-based OCT will revolutionize care of patients with nAMD, while skeptics question its real-world viability and point out its potential drawbacks. This article delves into the dichotomy, presenting the "pro" argument highlighting the transformative potential of home OCT and the "con" perspective, which scrutinizes the limitations and challenges to adapting the technology to the real-world setting. By exploring both sides of the discourse, we aim to address the promises and complexities surrounding the role of home OCT in the management of nAMD.},
}
@article {pmid38702879,
year = {2024},
author = {Lüdtke, L and Ittermann, T and Großjohann, R and Jürgens, C and Völzke, H and Tost, F and Stahl, A},
title = {Risk Factors of Age-Related Macular Degeneration in a Population-Based Study: Results from SHIP-TREND-1 (Study of Health in Pomerania-TREND-1).},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {30},
number = {},
pages = {e943140},
pmid = {38702879},
issn = {1643-3750},
mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; Aged ; Risk Factors ; Female ; Germany/epidemiology ; Middle Aged ; Aged, 80 and over ; Adult ; Cohort Studies ; },
abstract = {BACKGROUND Age-related macular degeneration (AMD) is the most common cause of visual impairment in the elderly population in industrialized countries. The Study of Health in Pomerania (SHIP) with its cohort SHIP-TREND was designed to investigate risk factors and clinical disorders in the general population of northeast Germany. This work focused on the first follow-up of SHIP-TREND and determined associated modifiable risk factors of AMD. Modifying risk factors is important to slow the progression of early AMD as there is currently no treatment for the late stage of geographic atrophy. Understanding AMD-associated risk factors also plays an important role in the development of therapeutic concepts. MATERIAL AND METHODS Between 2016 and 2019, data were collected from a total of 2507 initially randomly selected subjects from the general population aged 28 to 89 years. Non-mydriatic fundus photography of the right eye was performed in 2489 subjects. Grading of AMD was performed using the Rotterdam classification system. RESULTS We included 1418 gradable fundus photographs in the analysis. The risk of AMD changes increased with age and was positively correlated with HDL cholesterol, fT3, and low educational level. In men, BMI and cigarette smoking were also positively associated with AMD changes. CONCLUSIONS This study emphasizes the consideration of various metabolic pathways for the development of therapeutic concepts.},
}
@article {pmid38698112,
year = {2024},
author = {Kajita, K and Nishida, M and Kurimoto, Y and Yokota, S and Sugita, S and Semba, T and Shirae, S and Hayashi, N and Ozaki, A and Miura, Y and Maeda, A and Mitamura, Y and Takahashi, M and Mandai, M},
title = {Graft cell expansion from hiPSC-RPE strip after transplantation in primate eyes with or without RPE damage.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {10044},
pmid = {38698112},
issn = {2045-2322},
support = {Grant number JP21bm0204002//Japan Agency for Medical Research and Development/ ; },
mesh = {Animals ; *Retinal Pigment Epithelium/transplantation/cytology ; *Macaca fascicularis ; Humans ; *Induced Pluripotent Stem Cells/cytology ; Macular Degeneration/pathology ; },
abstract = {Clinical studies using suspensions or sheets of human pluripotent cell-derived retinal pigment epithelial cells (hiPSC-RPE) have been conducted globally for diseases such as age-related macular degeneration. Despite being minimally invasive, cell suspension transplantation faces challenges in targeted cell delivery and frequent cell leakage. Conversely, although the RPE sheet ensures targeted delivery with correct cell polarity, it requires invasive surgery, and graft preparation is time-consuming. We previously reported hiPSC-RPE strips as a form of quick cell aggregate that allows for reliable cell delivery to the target area with minimal invasiveness. In this study, we used a microsecond pulse laser to create a local RPE ablation model in cynomolgus monkey eyes. The hiPSC-RPE strips were transplanted into the RPE-ablated and intact sites. The hiPSC-RPE strip stably survived in all transplanted monkey eyes. The expansion area of the RPE from the engrafted strip was larger at the RPE injury site than at the intact site with no tumorigenic growth. Histological observation showed a monolayer expansion of the transplanted RPE cells with the expression of MERTK apically and collagen type 4 basally. The hiPSC-RPE strip is considered a beneficial transplantation option for RPE cell therapy.},
}
@article {pmid38696843,
year = {2024},
author = {Li, Y and Guo, S and Wu, X and Wan, J and Guan, Y and Luo, C and Chen, Q and Jiang, H and Lin, H and Qian, H and Shi, W and Fan, W},
title = {Novel CCR3-targeted cyclic peptides as potential therapeutic agents for age-related macular degeneration via inhibiting angiogenesis and reducing retinal photoreceptor damage.},
journal = {Bioorganic chemistry},
volume = {147},
number = {},
pages = {107405},
doi = {10.1016/j.bioorg.2024.107405},
pmid = {38696843},
issn = {1090-2120},
mesh = {Animals ; *Peptides, Cyclic/chemistry/pharmacology/chemical synthesis ; *Macular Degeneration/drug therapy/pathology ; Mice ; *Receptors, CCR3/antagonists &amp; inhibitors/metabolism ; Humans ; Angiogenesis Inhibitors/pharmacology/chemical synthesis/chemistry ; Molecular Structure ; Structure-Activity Relationship ; Mice, Inbred C57BL ; Dose-Response Relationship, Drug ; Apoptosis/drug effects ; Choroidal Neovascularization/drug therapy/pathology/metabolism ; Photoreceptor Cells, Vertebrate/drug effects/pathology ; Angiogenesis ; },
abstract = {The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting CC motif chemokine receptor 3 (CCR3). Based on the binding mode of the N-terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development.},
}
@article {pmid38696228,
year = {2024},
author = {Kim, JH},
title = {Intraocular inflammation as a major adverse event of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration: from clinical trials to real-world practice.},
journal = {Expert opinion on drug safety},
volume = {23},
number = {6},
pages = {659-661},
doi = {10.1080/14740338.2024.2351468},
pmid = {38696228},
issn = {1744-764X},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Clinical Trials as Topic ; Inflammation/drug therapy ; Uveitis/drug therapy ; },
}
@article {pmid38696177,
year = {2024},
author = {Antaki, F and Chopra, R and Keane, PA},
title = {Vision-Language Models for Feature Detection of Macular Diseases on Optical Coherence Tomography.},
journal = {JAMA ophthalmology},
volume = {142},
number = {6},
pages = {573-576},
pmid = {38696177},
issn = {2168-6173},
support = {MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {*Tomography, Optical Coherence/methods ; Humans ; Cross-Sectional Studies ; Artificial Intelligence ; Macular Edema/diagnosis/diagnostic imaging ; Macula Lutea/diagnostic imaging/pathology ; Female ; Reproducibility of Results ; Male ; Diabetic Retinopathy/diagnosis ; Retinal Diseases/diagnosis ; Central Serous Chorioretinopathy/diagnosis ; Macular Degeneration/diagnosis ; Retinal Perforations/diagnosis/diagnostic imaging ; },
abstract = {IMPORTANCE: Vision-language models (VLMs) are a novel artificial intelligence technology capable of processing image and text inputs. While demonstrating strong generalist capabilities, their performance in ophthalmology has not been extensively studied.<br><br>OBJECTIVE: To assess the performance of the Gemini Pro VLM in expert-level tasks for macular diseases from optical coherence tomography (OCT) scans.<br><br>This was a cross-sectional diagnostic accuracy study evaluating a generalist VLM on ophthalmology-specific tasks using the open-source Optical Coherence Tomography Image Database. The dataset included OCT B-scans from 50 unique patients: healthy individuals and those with macular hole, diabetic macular edema, central serous chorioretinopathy, and age-related macular degeneration. Each OCT scan was labeled for 10 key pathological features, referral recommendations, and treatments. The images were captured using a Cirrus high definition OCT machine (Carl Zeiss Meditec) at Sankara Nethralaya Eye Hospital, Chennai, India, and the dataset was published in December 2018. Image acquisition dates were not specified.<br><br>EXPOSURES: Gemini Pro, using a standard prompt to extract structured responses on December 15, 2023.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was model responses compared against expert labels, calculating F1 scores for each pathological feature. Secondary outcomes included accuracy in diagnosis, referral urgency, and treatment recommendation. The model's internal concordance was evaluated by measuring the alignment between referral and treatment recommendations, independent of diagnostic accuracy.<br><br>RESULTS: The mean F1 score was 10.7% (95% CI, 2.4-19.2). Measurable F1 scores were obtained for macular hole (36.4%; 95% CI, 0-71.4), pigment epithelial detachment (26.1%; 95% CI, 0-46.2), subretinal hyperreflective material (24.0%; 95% CI, 0-45.2), and subretinal fluid (20.0%; 95% CI, 0-45.5). A correct diagnosis was achieved in 17 of 50 cases (34%; 95% CI, 22-48). Referral recommendations varied: 28 of 50 were correct (56%; 95% CI, 42-70), 10 of 50 were overcautious (20%; 95% CI, 10-32), and 12 of 50 were undercautious (24%; 95% CI, 12-36). Referral and treatment concordance were very high, with 48 of 50 (96%; 95 % CI, 90-100) and 48 of 49 (98%; 95% CI, 94-100) correct answers, respectively.<br><br>CONCLUSIONS AND RELEVANCE: In this study, a generalist VLM demonstrated limited vision capabilities for feature detection and management of macular disease. However, it showed low self-contradiction, suggesting strong language capabilities. As VLMs continue to improve, validating their performance on large benchmarking datasets will help ascertain their potential in ophthalmology.},
}
@article {pmid38694444,
year = {2024},
author = {Zhou, W and Chai, Y and Lu, S and Yang, Q and Tang, L and Zhou, D},
title = {Advances in the study of tissue-engineered retinal pigment epithelial cell sheets.},
journal = {Regenerative therapy},
volume = {27},
number = {},
pages = {419-433},
pmid = {38694444},
issn = {2352-3204},
abstract = {Regarded as the most promising treatment modality for retinal degenerative diseases, retinal pigment epithelium cell replacement therapy holds significant potential. Common retinal degenerative diseases, including Age-related Macular Degeneration, are frequently characterized by damage to the unit comprising photoreceptors, retinal pigment epithelium, and Bruch's membrane. The selection of appropriate tissue engineering materials, in conjunction with retinal pigment epithelial cells, for graft preparation, can offer an effective treatment for retinal degenerative diseases. This article presents an overview of the research conducted on retinal pigment epithelial cell tissue engineering, outlining the challenges and future prospects.},
}
@article {pmid38694318,
year = {2024},
author = {Shakeel, L and Khan, A and Akilimali, A},
title = {"Izervay (avacincaptad pegol): paving the way for vision preservation in geographic atrophy".},
journal = {Annals of medicine and surgery (2012)},
volume = {86},
number = {5},
pages = {2413-2416},
pmid = {38694318},
issn = {2049-0801},
abstract = {Age-related macular degeneration (AMD) is a progressive retinal disease that primarily affects the macula, leading to central vision loss and impaired color vision. Among its most severe forms is geographic atrophy (GA), which results in irreversible central blindness. While numerous risk factors, including age, smoking, and genetics, contribute to the development of AMD, effective treatment options for GA have been limited. This article centers on Izervay [avacincaptad pegol (ACP)], an FDA-approved drug designed to address the unmet medical needs of patients with GA secondary to AMD. The pathophysiology of GA involves oxidative damage, chronic inflammation, and cell death, primarily due to complement system dysregulation. Previous treatments for GA have shown limited efficacy, leaving patients searching for more effective solutions. Izervay, with its unique mechanism of action, inhibits complement protein C5, disrupting the formation of the membrane attack complex and slowing retinal cell degeneration. Clinical trials have demonstrated Izervay's ability to significantly reduce the growth of GA lesions, offering hope for improved outcomes. Additionally, the drug has exhibited a tolerable safety profile, with common side effects including conjunctival hemorrhage and increased intraocular pressure. Izervay represents a breakthrough in AMD treatment, offering the potential to preserve vision in those at risk of irreversible vision loss due to GA. While further research is necessary to evaluate long-term efficacy and accessibility, its approval opens new possibilities in AMD management, transforming the lives of individuals affected by this condition.},
}
@article {pmid38692502,
year = {2024},
author = {Achiron, A and Trivizki, O and Knyazer, B and Elbaz, U and Hecht, I and Jeon, S and Kanclerz, P and Tuuminen, R},
title = {The Effect of Blue-light Filtering Intraocular Lenses on the Development and Progression of Macular Atrophy in Eyes With Neovascular Age-related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {266},
number = {},
pages = {135-143},
doi = {10.1016/j.ajo.2024.04.018},
pmid = {38692502},
issn = {1879-1891},
mesh = {Humans ; Female ; Male ; Aged ; Retrospective Studies ; *Disease Progression ; *Tomography, Optical Coherence ; *Lenses, Intraocular ; *Visual Acuity/physiology ; *Wet Macular Degeneration/physiopathology/diagnosis/drug therapy ; Aged, 80 and over ; Follow-Up Studies ; Lens Implantation, Intraocular ; Phacoemulsification ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; Light ; },
abstract = {PURPOSE: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the development and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, clinical cohort study.<br><br>METHODS: The study included patients with nAMD with anti-vascular endothelial growth factor (VEGF) injections who underwent uneventful cataract surgery between 2007 and 2018 with follow-up until June 2023. Subsequent MA rates were compared between subjects who received a BLF IOL or a non-BLF IOL. All optical coherence tomography scans were manually reviewed in a masked manner regarding patient baseline variables and IOL status by an experienced research technician. By using Heidelberg software, the area of MA was manually evaluated and calculated (mm[2]) by the program. The overall risk of developing new-onset MA and the effect of IOL type on disease progression were assessed. Death was included as a censoring event.<br><br>RESULTS: Included were 373 eyes of 373 patients (mean age, 78.6 &#xb1; 6.7 years at surgery; 67.4% were female). BLF IOLs were implanted in 206 eyes, and non-BLF IOLs were implanted in 167 eyes with comparable follow-up times (3164 &#xb1; 1420 days vs 3180 &#xb1; 1403 days, respectively, P = .908) and other baseline parameters (age, gender, corrected distance visual acuity, macular thickness, cumulative number of anti-VEGF injections). Nine preexisting and 77 new-onset MA cases were detected, with similar distribution between BLF and non-BLF eyes (P = .598 and P = .399, respectively). Both univariate Kaplan-Meier (P = .366) and multivariate Cox regression analyses adjusted for age and gender showed that BLF-IOLs were comparable to non-BLF IOLs regarding hazard for new-onset MA (hazard ratio [HR], 1.236; 95% CI, 0.784-1.949; P = .363). Final MA area at the last visit was 5.14 &#xb1; 4.71 mm[2] for BLF IOLs and 8.56 &#xb1; 9.17 mm[2] for non-BLF IOLs (P = .028), with the mean annual MA area increase of 0.78 &#xb1; 0.84 mm[2] and 1.26 &#xb1; 1.32 mm[2], respectively (P = .042).<br><br>CONCLUSIONS: BLF IOLs did not show added benefit over non-BLF IOLs in terms of MA-free survival but were associated with less progression over time in a cohort of patients with nAMD.},
}
@article {pmid38691156,
year = {2024},
author = {Schmidt-Erfurth, U and Riedl, S},
title = {[Complement inhibition treatment for geographic atrophy (GA): functional and morphological efficacy and relevant biomarkers in clinical practice].},
journal = {Die Ophthalmologie},
volume = {121},
number = {6},
pages = {476-481},
pmid = {38691156},
issn = {2731-7218},
mesh = {Humans ; *Geographic Atrophy/drug therapy/metabolism ; *Tomography, Optical Coherence ; *Biomarkers ; *Complement Inactivating Agents/therapeutic use/pharmacology ; Treatment Outcome ; Retinal Pigment Epithelium/pathology/diagnostic imaging/metabolism ; },
abstract = {The approval of complement inhibitory therapeutic agents for the treatment of geographic atrophy (GA) has highlighted the need for reliable and reproducible measurement of disease progression and therapeutic efficacy. Due to its availability and imaging characteristics optical coherence tomography (OCT) is the method of choice. Using OCT analysis based on artificial intelligence (AI), the therapeutic efficacy of pegcetacoplan was demonstrated at the levels of both the retinal pigment epithelium (RPE) and photoreceptors (PR). Cloud-based solutions that enable monitoring of GA are already available.},
}
@article {pmid38691000,
year = {2024},
author = {Ashimori, A and Higashijima, F and Ogata, T and Sakuma, A and Hamada, W and Sunada, J and Aoki, R and Mikuni, M and Hayashi, K and Wakuta, M and Yoshimoto, T and Minamoto, A and Ko, JA and Kimura, K},
title = {HIF-1α-dependent upregulation of angiogenic factors by mechanical stimulation in retinal pigment epithelial cells.},
journal = {Disease models &amp; mechanisms},
volume = {17},
number = {4},
pages = {},
pmid = {38691000},
issn = {1754-8411},
support = {JP22K16972//Japan Society for the Promotion of Science/ ; //Yamaguchi University/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Animals ; *Up-Regulation ; *p38 Mitogen-Activated Protein Kinases/metabolism ; *Mice, Inbred C57BL ; *src-Family Kinases/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Stress, Mechanical ; Signal Transduction ; Mice ; Cell Line ; Angiogenesis Inducing Agents/metabolism ; Epithelial Cells/metabolism ; Humans ; },
abstract = {Mechanical stimulation as a mimic of drusen formation in the eye increases the expression of angiogenic factors in retinal pigment epithelial (RPE) cells, but the underlying molecular mechanisms remain unclear. We investigated and characterized the effects of mechanical stimulation on the expression of angiogenic factors in RPE cells both in vitro and in a mouse model. Mechanical stimulation increased the expression of vascular endothelial growth factor (VEGF, encoded by VEGFA) and other angiogenesis-related genes in cultured RPE1 cells. The presence of hypoxia-inducible factor 1α (HIF-1α, encoded by HIF1A) was also increased, and both knockdown of HIF-1α and treatment with the HIF-1α inhibitor CAY10585 attenuated the effect of mechanical stimulation on angiogenesis factor gene expression. Signaling by the tyrosine kinase SRC and p38 mitogen-activated protein kinase was involved in HIF-1α activation and consequent angiogenesis-related gene expression induced by mechanical stimulation. Our results suggest that SRC-p38 and HIF-1α signaling are involved in the upregulation of angiogenic factors in RPE cells by mechanical stimulation. Such in vivo suppression of upregulated expression of angiogenesis-related genes by pharmacological inhibitors of HIF-1α suggests a new potential approach to the treatment of age-related macular degeneration.},
}
@article {pmid38690727,
year = {2024},
author = {Wilke, GA and Apte, RS},
title = {Complement regulation in the eye: implications for age-related macular degeneration.},
journal = {The Journal of clinical investigation},
volume = {134},
number = {9},
pages = {},
pmid = {38690727},
issn = {1558-8238},
mesh = {Humans ; *Macular Degeneration/immunology/pathology ; *Complement System Proteins/immunology/metabolism ; *Complement Activation/immunology ; Animals ; Eye/immunology/pathology ; },
abstract = {Careful regulation of the complement system is critical for enabling complement proteins to titrate immune defense while also preventing collateral tissue damage from poorly controlled inflammation. In the eye, this balance between complement activity and inhibition is crucial, as a low level of basal complement activity is necessary to support ocular immune privilege, a prerequisite for maintaining vision. Dysregulated complement activation contributes to parainflammation, a low level of inflammation triggered by cellular damage that functions to reestablish homeostasis, or outright inflammation that disrupts the visual axis. Complement dysregulation has been implicated in many ocular diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). In the last two decades, complement activity has been the focus of intense investigation in AMD pathogenesis, leading to the development of novel therapeutics for the treatment of atrophic AMD. This Review outlines recent advances and challenges, highlighting therapeutic approaches that have advanced to clinical trials, as well as providing a general overview of the complement system in the posterior segment of the eye and selected ocular diseases.},
}
@article {pmid38689123,
year = {2024},
author = {Vallino, V and Berni, A and Coletto, A and Serafino, S and Bandello, F and Reibaldi, M and Borrelli, E},
title = {Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {11},
pages = {3421-3436},
pmid = {38689123},
issn = {1435-702X},
mesh = {Humans ; *Biomarkers/metabolism ; Disease Progression ; Fluorescein Angiography/methods ; Fundus Oculi ; *Geographic Atrophy/diagnosis ; *Macular Degeneration/diagnosis ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; },
abstract = {BACKGROUND: Geographic atrophy (GA) is an advanced, irreversible, and progressive form of age-related macular degeneration (AMD). Structural optical coherence tomography (OCT) and OCT angiography (OCTA) have been largely used to characterize this stage of AMD and, more importantly, to define biomarkers associated with the development and progression of GA in AMD.<br><br>METHODS: Articles pertaining to OCT and OCTA biomarkers related to the development and progression of GA with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility.<br><br>RESULTS: Previous reports have highlighted various OCT and OCTA biomarkers linked to the onset and advancement of GA. These biomarkers encompass characteristics such as the size, volume, and subtype of drusen, the presence of hyperreflective foci, basal laminar deposits, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), persistent choroidal hypertransmission defects, and the existence of subretinal drusenoid deposits (also referred to as reticular pseudodrusen). Moreover, biomarkers associated with the progression of GA include thinning of the outer retina, photoreceptor degradation, the distance between retinal pigment epithelium and Bruch's membrane, and choriocapillaris loss.<br><br>CONCLUSION: The advent of novel treatment strategies for GA underscores the heightened need for prompt diagnosis and precise monitoring of individuals with this condition. The utilization of structural OCT and OCTA becomes essential for identifying distinct biomarkers associated with the initiation and progression of GA.},
}
@article {pmid38687492,
year = {2024},
author = {Saßmannshausen, M and Döngelci, S and Vaisband, M and von der Emde, L and Sloan, KR and Hasenauer, J and Holz, FG and Schmitz-Valckenberg, S and Ach, T},
title = {Spatially Resolved Association of Structural Biomarkers on Retinal Function in Non-Exudative Age-Related Macular Degeneration Over 4 Years.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {4},
pages = {45},
pmid = {38687492},
issn = {1552-5783},
support = {R01 EY027948/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Aged ; Male ; Middle Aged ; *Tomography, Optical Coherence/methods ; *Visual Field Tests ; *Disease Progression ; *Visual Acuity/physiology ; *Visual Fields/physiology ; Macular Degeneration/physiopathology/diagnosis ; Retinal Drusen/physiopathology/diagnosis ; Biomarkers ; Follow-Up Studies ; Retinal Pigment Epithelium/pathology/physiopathology ; Night Vision/physiology ; Retina/physiopathology/diagnostic imaging/pathology ; Aged, 80 and over ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To longitudinally assess the impact of high-risk structural biomarkers for natural disease progression in non-exudative age-related macular degeneration (AMD) on spatially resolved mesopic and scotopic fundus-controlled perimetry testing.<br><br>METHODS: Multimodal retinal imaging data and fundus-controlled perimetry stimuli points were semiautomatically registered according to landmark correspondences at each annual visit over a period of up to 4 years. The presence of sub-RPE drusen, subretinal drusenoid deposits, pigment epithelium detachments (PEDs), hyper-reflective foci (HRF), vitelliform lesions, refractile deposits, and incomplete RPE and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) were graded at each stimulus position and visit. Localized retinal layer thicknesses were extracted. Mixed-effect models were used for structure-function correlation.<br><br>RESULTS: Fifty-four eyes of 49 patients with non-exudative AMD (mean age, 70.7 &#xb1; 9.1&#xa0;years) and 27 eyes of 27 healthy controls (mean age, 63.4 &#xb1; 8.9&#xa0;years) were included. During study course, presence of PED had the highest functional impact with a mean estimated loss of -1.30 dB (P < 0.001) for mesopic and -1.23 dB (P < 0.001) for scotopic testing, followed by HRF with -0.89 dB (mesopic, P = 0.001) and -0.87 dB (scotopic, P = 0.005). Subretinal drusenoid deposits were associated with a stronger visual impairment (mesopic, -0.38 dB; P = 0.128; scotopic, -0.37 dB; P = 0.172) compared with sub-RPE drusen (-0.22 dB, P = 0.0004; -0.18 dB, P = 0.006). With development of c-RORA, scotopic retinal sensitivity further significantly decreased (-2.15 dB; P = 0.02). Thickening of the RPE-drusen-complex and thinning of the outer nuclear layer negatively impacted spatially resolved retinal sensitivity.<br><br>CONCLUSIONS: The presence of PED and HRF had the greatest prognostic impact on progressive point-wise sensitivity losses. Higher predominant rod than cone-mediated localized retinal sensitivity losses with early signs of retinal atrophy development indicate photoreceptor preservation as a potential therapeutic target for future interventional AMD trials.},
}
@article {pmid38684968,
year = {2024},
author = {Wu, J and Zhang, Y and Xu, X},
title = {Association between ambient air pollution and age-related macular degeneration: a meta-analysis.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {202},
pmid = {38684968},
issn = {1471-2415},
mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; *Air Pollution/adverse effects ; Particulate Matter/adverse effects ; Risk Factors ; Air Pollutants/adverse effects ; Odds Ratio ; Ozone/adverse effects ; Nitrogen Dioxide/adverse effects/analysis ; Environmental Exposure/adverse effects ; },
abstract = {BACKGROUND: Several epidemiological studies have investigated the association between ambient air pollution and age-related macular degeneration (AMD). However, a consensus has not yet been reached. Our meta-analysis aimed to clarify this association.<br><br>METHODS: Databases, including PubMed, EMBASE, and Web of Science, were searched for relevant studies from 01 January 2000 to 30 January 2024. English-language, peer-reviewed studies using cross-sectional, prospective, or retrospective cohorts and case-control studies exploring this relationship were included. Two authors independently extracted data and assessed study quality. A random-effects model was used to calculate pooled covariate-adjusted odds ratios. Heterogeneity across studies was also tested.<br><br>RESULTS: We identified 358 relevant studies, of which eight were included in the meta-analysis. Four studies evaluated the association between particulate matter less than 2.5&#xa0;&#x3bc;m in diameter (PM2.5) and AMD, and three studies explored the relationship between nitrogen dioxide (NO2) or ozone (O3) and AMD. The pooled odds ratios were 1.16 (95% confidence interval [CI]: 1.11-1.21), 1.17 (95% CI: 1.09-1.25), and 1.06 (95% CI: 1.05-1.07), respectively.<br><br>CONCLUSION: Current evidence suggests a concomitant positive but not causal relationship between PM2.5, NO2, or O3 and AMD risk.},
}
@article {pmid38683564,
year = {2024},
author = {Lim, RR and Shirali, S and Rowlan, J and Engel, AL and Nazario, M and Gonzalez, K and Tong, A and Neitz, J and Neitz, M and Chao, JR},
title = {CFH Haploinsufficiency and Complement Alterations in Early-Onset Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {4},
pages = {43},
pmid = {38683564},
issn = {1552-5783},
support = {P30 EY001730/EY/NEI NIH HHS/United States ; R01 EY034364/EY/NEI NIH HHS/United States ; U01 EY034591/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Complement Factor H/genetics/metabolism ; *Haploinsufficiency ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/genetics/metabolism ; Male ; Female ; Induced Pluripotent Stem Cells/metabolism ; Complement C3b Inactivator Proteins/genetics/metabolism ; Complement Activation/genetics ; Pedigree ; Blotting, Western ; Complement System Proteins/metabolism/genetics ; Retinal Drusen/genetics/metabolism ; Middle Aged ; *Muscle Proteins ; *Intracellular Signaling Peptides and Proteins ; *LIM Domain Proteins ; },
abstract = {PURPOSE: Complement dysregulation is a key component in the pathogenesis of age-related macular degeneration (AMD) and related diseases such as early-onset macular drusen (EOMD). Although genetic variants of complement factor H (CFH) are associated with AMD risk, the impact of CFH and factor H-like protein 1 (FHL-1) expression on local complement activity in human retinal pigment epithelium (RPE) remains unclear.<br><br>METHODS: We identified a novel CFH variant in a family with EOMD and generated patient induced pluripotent stem cell (iPSC)-derived RPE cells. We assessed CFH and FHL-1 co-factor activity through C3b breakdown assays and measured complement activation by immunostaining for membrane attack complex (MAC) formation. Expression of CFH, FHL-1, local alternative pathway (AP) components, and regulators of complement activation (RCA) in EOMD RPE cells was determined by quantitative PCR, western blot, and immunostaining. Isogenic EOMD (cEOMD) RPE was generated using CRISPR/Cas9 gene editing.<br><br>RESULTS: The CFH variant (c.351-2A>G) resulted in loss of CFH and FHL-1 expression and significantly reduced CFH and FHL-1 protein expression (&#x223c;50%) in EOMD iPSC RPE cells. These cells exhibited increased MAC deposition upon exposure to normal human serum. Under inflammatory or oxidative stress conditions, CFH and FHL-1 expression in EOMD RPE cells paralleled that of controls, whereas RCA expression, including MAC formation inhibitors, was elevated. CRISPR/Cas9 correction restored CFH/FHL-1 expression and mitigated alternative pathway complement activity in cEOMD RPE cells.<br><br>CONCLUSIONS: Identification of a novel CFH variant in patients with EOMD resulting in reduced CFH and FHL-1 and increased local complement activity in EOMD iPSC RPE supports the involvement of CFH haploinsufficiency in EOMD pathogenesis.},
}
@article {pmid38682722,
year = {2024},
author = {Mi, Y and Zhu, Q and Zheng, X and Wan, M},
title = {The protective role of water intake in age-related eye diseases: insights from a Mendelian randomization study.},
journal = {Food &amp; function},
volume = {15},
number = {9},
pages = {5147-5157},
doi = {10.1039/d4fo01559b},
pmid = {38682722},
issn = {2042-650X},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Drinking ; *Macular Degeneration/genetics/epidemiology ; *Genome-Wide Association Study ; Male ; Female ; Aged ; Eye Diseases/genetics/epidemiology ; Cataract/genetics/prevention &amp; control/epidemiology ; Glaucoma/genetics/epidemiology ; Middle Aged ; Diabetic Retinopathy/genetics/epidemiology/prevention &amp; control ; Polymorphism, Single Nucleotide ; },
abstract = {Age-related eye diseases (AREDs), including age-related cataracts (ARCs), age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, are a leading cause of visual loss globally. This study aimed to explore the effects of dietary water intake on AREDs using Mendelian randomization. In the European population, genome-wide association study (GWAS) summary statistics of water intake and AREDs were obtained from the UK Biobank database and the FinnGen Consortium, respectively. The causal associations between water intake and ARED risks were explored by univariable and multivariable MR analyses, followed by sensitivity analyses to test the robustness of the results and detect potential pleiotropy bias. Water intake was associated with reduced risks of ARCs (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.46-0.83; P = 1.44 × 10[-3]) and DR (OR: 0.52; 95% CI: 0.36-0.76; P = 5.47 × 10[-4]), and a suggestive reduced risk of AMD (OR: 0.42; 95% CI: 0.20-0.88; P = 2.18 × 10[-2]). Water intake had no effect on glaucoma (OR: 1.16; 95% CI: 0.72-1.88; P = 0.549). After adjusting confounders, the causal effects of water intake on ARCs and DR persisted. Our study provides evidence of the preventive role of water intake in ARCs and DR from a genetic perspective.},
}
@article {pmid38680694,
year = {2024},
author = {Ye, ST and Shang, XW and Huang, Y and Zhu, S and Zhu, ZT and Zhang, XL and Wang, W and Tang, SL and Ge, ZY and Yang, XH and He, MG},
title = {Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity.},
journal = {World journal of diabetes},
volume = {15},
number = {4},
pages = {697-711},
pmid = {38680694},
issn = {1948-9358},
abstract = {BACKGROUND: The importance of age on the development of ocular conditions has been reported by numerous studies. Diabetes may have different associations with different stages of ocular conditions, and the duration of diabetes may affect the development of diabetic eye disease. While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality, whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored. It is unclear which types of diabetes are more predictive of ocular conditions.<br><br>AIM: To examine associations between the age of diabetes diagnosis and the incidence of cataract, glaucoma, age-related macular degeneration (AMD), and vision acuity.<br><br>METHODS: Our analysis was using the UK Biobank. The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis, and 6689 diabetic participants and 13378 controls for vision analysis. Ocular diseases were identified using inpatient records until January 2021. Vision acuity was assessed using a chart.<br><br>RESULTS: During a median follow-up of 11.0 years, 3874, 665, and 616 new cases of cataract, glaucoma, and AMD, respectively, were identified. A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age. Individuals with type 2 diabetes (T2D) diagnosed at < 45 years [HR (95%CI): 2.71 (1.49-4.93)], 45-49 years [2.57 (1.17-5.65)], 50-54 years [1.85 (1.13-3.04)], or 50-59 years of age [1.53 (1.00-2.34)] had a higher risk of AMD independent of glycated haemoglobin. T2D diagnosed < 45 years [HR (95%CI): 2.18 (1.71-2.79)], 45-49 years [1.54 (1.19-2.01)], 50-54 years [1.60 (1.31-1.96)], or 55-59 years of age [1.21 (1.02-1.43)] was associated with an increased cataract risk. T2D diagnosed < 45 years of age only was associated with an increased risk of glaucoma [HR (95%CI): 1.76 (1.00-3.12)]. HRs (95%CIs) for AMD, cataract, and glaucoma associated with type 1 diabetes (T1D) were 4.12 (1.99-8.53), 2.95 (2.17-4.02), and 2.40 (1.09-5.31), respectively. In multivariable-adjusted analysis, individuals with T2D diagnosed < 45 years of age [&#x3b2; 95%CI: 0.025 (0.009,0.040)] had a larger increase in LogMAR. The &#x3b2; (95%CI) for LogMAR associated with T1D was 0.044 (0.014, 0.073).<br><br>CONCLUSION: The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.},
}
@article {pmid38679743,
year = {2024},
author = {Hong, SH and Kim, HD},
title = {Central retinal artery occlusion after intravitreal brolucizumab injection for treatment-naïve neovascular age-related macular degeneration; a case report.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {200},
pmid = {38679743},
issn = {1471-2415},
support = {N/A//Soonchunhyang University Research Fund/ ; },
mesh = {Humans ; Male ; Aged ; *Intravitreal Injections ; *Retinal Artery Occlusion/chemically induced/diagnosis ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; *Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use/administration &amp; dosage ; *Tomography, Optical Coherence ; Fluorescein Angiography ; Wet Macular Degeneration/drug therapy/diagnosis ; Visual Acuity ; },
abstract = {BACKGROUND: To report a case of central retinal artery occlusion (CRAO) after intravitreal injection of brolucizumab for a treatment-naïve neovascular age-related macular degeneration (nAMD) patient without comorbid cardiovascular disease history.<br><br>CASE PRESENTATION: A 79-year-old Asian male without a cardiovascular disease history such as diabetes or hypertension underwent three times of monthly consecutive intravitreal brolucizumab injections for treatment of progressed nAMD in his left eye. Two days after the third injection, the patient presented with acute painless visual loss. Typical retinal whitening with a cherry red spot was observed on the fundus photograph, and retinal swelling with hyper-reflectivity was also identified on the optical coherence tomography (OCT) scan. On the fundus fluorescein angiography, arm-to-retina time and arteriovenous transit time were remarkedly delayed, but clinical findings suggesting an intraocular inflammation (IOI) were not observed. Therefore, CRAO was diagnosed, and anterior chamber paracentesis was administrated immediately. However, there had been no improvement in visual acuity during the follow-up period of three months, despite prolonged oral steroid and anti-platelet agent medication.<br><br>CONCLUSIONS: In rare cases, patients without cardiovascular comorbidities can develop CRAO after intravitreal brolucizumab injection without gross evidence of IOI. Therefore, CRAO should always be in consideration and careful observation is required after intravitreal brolucizumab injection for nAMD patients with old age, even if the patient does not have any other cardiovascular disease history.},
}
@article {pmid38679293,
year = {2024},
author = {Faria, MJ and González-Méijome, JM and Real Oliveira, MECD and Carracedo, G and Lúcio, M},
title = {Recent advances and strategies for nanocarrier-mediated topical therapy and theranostic for posterior eye disease.},
journal = {Advanced drug delivery reviews},
volume = {210},
number = {},
pages = {115321},
doi = {10.1016/j.addr.2024.115321},
pmid = {38679293},
issn = {1872-8294},
mesh = {Humans ; *Drug Carriers/chemistry ; *Theranostic Nanomedicine/methods ; Nanoparticles ; Animals ; Drug Delivery Systems ; Eye Diseases/drug therapy ; Administration, Ophthalmic ; Administration, Topical ; },
abstract = {Posterior eye disorders, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, have a significant impact on human quality of life and are the primary cause of age-related retinal diseases among adults. There is a pressing need for innovative topical approaches to treat posterior eye disorders, as current methods often rely on invasive procedures with inherent risks. Limited success was attained in the realm of topical ophthalmic delivery through non-invasive means. Additionally, there exists a dearth of literature that delves into the potential of this approach for drug delivery and theranostic purposes, or that offers comprehensive design strategies for nanocarrier developers to surmount the significant physiological ocular barriers. This review offers a thorough and up-to-date state-of-the-art overview of 40 studies on therapeutic loaded nanocarriers and theranostic devices that, to the best of our knowledge, represent all successful works that reached posterior eye segments through a topical non-invasive administration. Most importantly, based on the successful literature studies, this review provides a comprehensive summary of the potential design strategies that can be implemented during nanocarrier development to overcome each ocular barrier.},
}
@article {pmid38679018,
year = {2024},
author = {Holekamp, N and Gentile, B and Giocanti-Aurégan, A and García-Layana, A and Peto, T and Viola, F and Kertes, PJ and Mirt, M and Kotecha, A and Lambert, J and Lewis, HB and Chi, GC},
title = {Patient Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {311-321},
doi = {10.1159/000538975},
pmid = {38679018},
issn = {1423-0259},
mesh = {Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Female ; *Macular Edema/drug therapy ; Cross-Sectional Studies ; Aged ; *Diabetic Retinopathy/drug therapy ; *Visual Acuity ; *Intravitreal Injections ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy/physiopathology ; *Patient Satisfaction ; Surveys and Questionnaires ; Ranibizumab/administration &amp; dosage ; Middle Aged ; Aged, 80 and over ; Tomography, Optical Coherence ; Bevacizumab/administration &amp; dosage/therapeutic use ; Treatment Outcome ; },
abstract = {INTRODUCTION: Understanding patient perspectives of treatment may improve adherence and outcomes. This study explored real-world patient experiences with anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This multinational, non-interventional, quantitative, cross-sectional, observational survey assessed treatment barriers/burden, patient-reported visual functioning, and treatment satisfaction in DME and nAMD patients in the USA, the UK, Canada, France, Italy, and Spain. Treatment patterns and visual outcomes were extracted from medical charts. Regression models evaluated relationships between adherence, total missed visits, number of anti-VEGF injections, and clinical and patient-reported outcomes for visual functioning. Association between treatment satisfaction and aspects of burden were assessed.<br><br>RESULTS: The survey was completed by 183 DME and 391 nAMD patients. Patients had moderately high vision-related functioning (25-item National Eye Institute Visual Functioning Questionnaire score: mean = 74.8) and were satisfied with their current treatment (mean total score: Macular Disease Treatment Satisfaction Questionnaire = 59.2; Retinopathy Treatment Satisfaction Questionnaire = 61.3). Treatment satisfaction scores were worse with higher time-related impacts of treatment (nAMD/DME), higher impacts on finances and daily life (nAMD), negative impacts on employment and lower expectations for treatment effectiveness (DME). Most patients reported &#x2265;1 barrier (66.1% DME, 49.2% nAMD patients) related to treatment (35.0%), clinic (32.6%), and COVID-19 (21.1%). Moreover, 44.9% of patients reported some impairment in activities of daily living. Work absenteeism was observed among >60% of working patients. Nearly one-quarter (24.2%) of patients needed &#x2265;1 day to recover from intravitreal injections; most reported &#x2265;30 min of travel time (73.7%) and clinic wait time (54.2%). In unadjusted univariable analyses, treatment adherence (vs. nonadherence) was related to higher most recent visual acuity (&#x3b2; = 8.98 letters; CI, 1.34-16.62) and lower odds of visual acuity below driving vision (&#x2264;69 letters) (OR = 0.50; CI, 0.25-1.00).<br><br>CONCLUSION: More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes.},
}
@article {pmid38678728,
year = {2024},
author = {Tyagi, S and Katara, P},
title = {A metagenome-wide association study of gut microbiome in patients with AMD, ASD, RA, T2D &amp; VKH diseases.},
journal = {Computational biology and chemistry},
volume = {110},
number = {},
pages = {108076},
doi = {10.1016/j.compbiolchem.2024.108076},
pmid = {38678728},
issn = {1476-928X},
mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Arthritis, Rheumatoid/microbiology ; *Autism Spectrum Disorder/microbiology ; *Diabetes Mellitus, Type 2/microbiology ; *Macular Degeneration/microbiology/genetics ; Metagenome ; Metagenomics ; },
abstract = {Clinical studies have already illustrated the associations between gut microbes and diseases, yet fundamental questions remain unclear that how we can universalize this knowledge. Considering the important role of human gut microbial composition in maintaining overall health, it is important to understand the microbial diversity and altered disease conditions of the human gut. Metagenomics provides a way to analyze and understand the microbes and their role in a community manner. It provides qualitative as well as quantitative measurements, in terms of relative abundance. Various studies are already going on to find out the association between microbes and diseases; still, the mined knowledge is limited. Considering the current scenario, using the targeted metagenomics approach, we analyzed the gut microbiome of 99 samples from healthy and diseased individuals. Our metagenomic analysis mainly targeted five diseased microbiomes (i.e., Age-related macular degeneration, Autism spectrum disorder, Rheumatoid arthritis, Type 2 diabetes and Vogt-Koyanagi harada), with compare to healthy microbiome, and reported disease-associated microbiome shift in different conditions.},
}
@article {pmid38678148,
year = {2024},
author = {Nakamura, S and Yamamoto, R and Matsuda, T and Yasuda, H and Nishinaka, A and Takahashi, K and Inoue, Y and Kuromitsu, S and Shimazawa, M and Goto, M and Narumiya, S and Hara, H},
title = {Sphingosine-1-phosphate receptor 1/5 selective agonist alleviates ocular vascular pathologies.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {9700},
pmid = {38678148},
issn = {2045-2322},
mesh = {Animals ; Humans ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Mice ; *Disease Models, Animal ; Sphingosine-1-Phosphate Receptors/metabolism/agonists ; Endothelial Cells/drug effects/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Cell Proliferation/drug effects ; Mice, Inbred C57BL ; Receptors, Lysosphingolipid/agonists/metabolism ; Male ; },
abstract = {Ocular abnormal angiogenesis and edema are featured in several ocular diseases. S1P signaling via S1P1 likely is part of the negative feedback mechanism necessary to maintain vascular health. In this study, we conducted pharmacological experiments to determine whether ASP4058, a sphingosine 1-phosphate receptor 1/5 (S1P1/5) agonist, is useful in abnormal vascular pathology in the eye. First, human retinal microvascular endothelial cells (HRMECs) were examined using vascular endothelial growth factor (VEGF)-induced cell proliferation and hyperpermeability. ASP4058 showed high affinity and inhibited VEGF-induced proliferation and hyperpermeability of HRMECs. Furthermore, S1P1 expression and localization changes were examined in the murine laser-induced choroidal neovascularization (CNV) model, a mouse model of exudative age-related macular degeneration, and the efficacy of ASP4058 was verified. In the CNV model mice, S1P1 tended to decrease in expression immediately after laser irradiation and colocalized with endothelial cells and Müller glial cells. Oral administration of ASP4058 also suppressed vascular hyperpermeability and CNV, and the effect was comparable to that of the intravitreal administration of aflibercept, an anti-VEGF drug. Next, efficacy was also examined in a retinal vein occlusion (RVO) model in which retinal vascular permeability was increased. ASP4058 dose-dependently suppressed the intraretinal edema. In addition, it suppressed the expansion of the perfusion area observed in the RVO model. ASP4058 also suppressed the production of VEGF in the eye. Collectively, ASP4058 can be a potential therapeutic agent that normalizes abnormal vascular pathology, such as age-related macular degeneration and RVO, through its direct action on endothelial cells.},
}
@article {pmid38678114,
year = {2024},
author = {Russell, MW and Kumar, M and Li, A and Singh, RP and Talcott, KE},
title = {Incidence of ocular pathology following bariatric surgery for with morbid obesity across a large United States National Database.},
journal = {Eye (London, England)},
volume = {38},
number = {13},
pages = {2603-2609},
pmid = {38678114},
issn = {1476-5454},
mesh = {Humans ; *Obesity, Morbid/surgery/epidemiology/complications ; Male ; Retrospective Studies ; Female ; United States/epidemiology ; *Bariatric Surgery/adverse effects ; Incidence ; Middle Aged ; Adult ; *Databases, Factual ; *Eye Diseases/epidemiology/etiology ; Aged ; Postoperative Complications/epidemiology ; Diabetic Retinopathy/epidemiology ; Glaucoma/epidemiology ; Macular Degeneration/epidemiology/etiology ; Blindness/epidemiology/etiology ; },
abstract = {BACKGROUND/OBJECTIVES: Bariatric surgery, as indicated for treatment of morbid obesity, has been studied in association with short term effects on ocular pathology. However, effects of surgery on postoperative disease incidence is largely unknown.<br><br>SUBJECTS/METHODS: In this retrospective cohort study, the TriNetX United States Collaborative Network national database, was queried for patients with an ICD-10 code for morbid obesity and a procedural code for bariatric surgery. Patients were propensity score matched across baseline demographics at the time of surgery and compared to those presenting with an ICD10 code for morbid obesity with no records of a procedural code for bariatric surgery, identifying 42,408 patients per cohort. New diagnoses or procedural codes found after the surgical index date for diabetic retinopathy, age-related macular degeneration, glaucoma, low vision, and blindness along with pertinent treatment metrics were monitored.<br><br>RESULTS: Bariatric surgery was found to be associated with reduced future risk of diabetic retinopathy (RR: 0.283; 95% CI: 0.252-0.319), macular edema (RR: 0.224; 95% CI: 0.170-0.297), vitreous hemorrhage (RR: 0.459; 95% CI: 0.323-0.653), ocular hypertension (RR: 0.387; 95% CI: 0.387-0.487), glaucoma (RR: 0.360; 95% CI: 0.326-0.399), use of ocular pressure lowering medications (RR: 0.565; 95% CI: 0.496-0.644), age-related macular degeneration (RR: 0.628; 95% CI: 0.447-0.882), cataract surgery (RR: 0.524; 95% CI: 0.448-0.612), and low vision and blindness (RR: 0.328; 95% CI: 0.294-0.365) compared to patients not surgically managed.<br><br>CONCLUSIONS: The present analysis comprising a large US cohort of patients suggests that bariatric surgery is associated with a decreased risk of future ocular morbidity and mortality.},
}
@article {pmid38677638,
year = {2024},
author = {Velaga, SB and Alagorie, AR and Emamverdi, M and Ashrafkhorasani, M and Habibi, A and Nittala, MG and Sing, G and Haines, J and Pericak-Vance, MA and Stambolian, D and Sadda, SR},
title = {Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: An Amish Eye Study Analysis.},
journal = {American journal of ophthalmology},
volume = {265},
number = {},
pages = {80-87},
doi = {10.1016/j.ajo.2024.04.024},
pmid = {38677638},
issn = {1879-1891},
support = {R01 EY030614/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Ganglion Cells/pathology ; Cross-Sectional Studies ; Prospective Studies ; Female ; Male ; Aged ; *Nerve Fibers/pathology ; *Tomography, Optical Coherence/methods ; Middle Aged ; Macular Degeneration/diagnosis/physiopathology ; Aged, 80 and over ; Visual Acuity/physiology ; },
abstract = {PURPOSE: To compare the ganglion cell complex (GCC) thickness in eyes with age-related macular degeneration (AMD) vs healthy controls in an elderly Amish population.<br><br>DESIGN: Prospective cross-sectional study.<br><br>METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects underwent imaging with the Cirrus HD-OCT (Carl Zeiss Meditec Inc) using a macular cube protocol of 512 &#xd7; 128 scans (128 horizontal B-scans, each comprising 512 A-scans) over a 6 mm &#xd7; 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the ganglion cell layer (GCL) and the IPL. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of 6 sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system.<br><br>RESULTS: Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of 1294 subjects had all required imaging studies of sufficient quality and were included in the final analysis. Of these, 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (P < .001) thinner in AMD subjects (73.71 &#xb1; SD; 13.77 &#xb5;m) compared to normals (77.97 &#xb1; 10.42 &#xb5;m). An independent t test showed that the early AMD (75.03 &#xb1; 12.45 &#xb5;m) and late AMD (61.64 &#xb1; 21.18 &#xb5;m) groups (among which eyes with geographic atrophy [GA] had the lowest thickness, of 58.10 &#xb1; 20.27 &#xb5;m) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant differences in average GCC thickness between early AMD and intermediate AMD (76.36 &#xb1; 9.25 &#xb5;m) eyes.<br><br>CONCLUSIONS: The GCC thickness in AMD eyes is reduced compared to normal eyes; however, the relationship is complex, with the greatest reduction in late AMD eyes (particularly eyes with GA) but no difference between early and intermediate AMD eyes.},
}
@article {pmid38676042,
year = {2024},
author = {Niu, Z and Deng, Z and Gao, W and Bai, S and Gong, Z and Chen, C and Rong, F and Li, F and Ma, L},
title = {FNeXter: A Multi-Scale Feature Fusion Network Based on ConvNeXt and Transformer for Retinal OCT Fluid Segmentation.},
journal = {Sensors (Basel, Switzerland)},
volume = {24},
number = {8},
pages = {},
pmid = {38676042},
issn = {1424-8220},
support = {KCXFZ20211020163813019//Shenzhen Sustainable Development Project/ ; JCYJ20230807094803007//Shenzhen Basic Research Project (Natural Science Fund)/ ; },
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Retina/diagnostic imaging ; Algorithms ; Neural Networks, Computer ; Image Processing, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging/pathology ; },
abstract = {The accurate segmentation and quantification of retinal fluid in Optical Coherence Tomography (OCT) images are crucial for the diagnosis and treatment of ophthalmic diseases such as age-related macular degeneration. However, the accurate segmentation of retinal fluid is challenging due to significant variations in the size, position, and shape of fluid, as well as their complex, curved boundaries. To address these challenges, we propose a novel multi-scale feature fusion attention network (FNeXter), based on ConvNeXt and Transformer, for OCT fluid segmentation. In FNeXter, we introduce a novel global multi-scale hybrid encoder module that integrates ConvNeXt, Transformer, and region-aware spatial attention. This module can capture long-range dependencies and non-local similarities while also focusing on local features. Moreover, this module possesses the spatial region-aware capabilities, enabling it to adaptively focus on the lesions regions. Additionally, we propose a novel self-adaptive multi-scale feature fusion attention module to enhance the skip connections between the encoder and the decoder. The inclusion of this module elevates the model's capacity to learn global features and multi-scale contextual information effectively. Finally, we conduct comprehensive experiments to evaluate the performance of the proposed FNeXter. Experimental results demonstrate that our proposed approach outperforms other state-of-the-art methods in the task of fluid segmentation.},
}
@article {pmid38675608,
year = {2024},
author = {Yang, C and Ge, L and Yu, X and Lazarovici, P and Zheng, W},
title = {Artemisinin Confers Cytoprotection toward Hydrogen Peroxide-Induced Cell Apoptosis in Retinal Pigment Epithelial Cells in Correlation with the Increased Acetylation of Histone H4 at Lysine 8.},
journal = {Molecules (Basel, Switzerland)},
volume = {29},
number = {8},
pages = {},
pmid = {38675608},
issn = {1420-3049},
support = {31771128 and 31371088//National Natural Science Foundation of China/ ; 0127/2019/A3, 0113/2018/A3, 0038/2020/AMJ, and 0104/2022/A2//Science and Technology Development Fund/ ; 2022-Natural Science Foundation//Guangdong Provincial Funding Committee for Basic and Applied Fundamental Research/ ; MYRG2018-00134-FHS and MYRG2020-00158-FHS//University of Macau/ ; },
mesh = {Humans ; *Histones/metabolism ; *Apoptosis/drug effects ; Acetylation/drug effects ; *Hydrogen Peroxide/pharmacology ; *Artemisinins/pharmacology ; *Retinal Pigment Epithelium/drug effects/metabolism/cytology ; *Lysine/metabolism ; *Cell Survival/drug effects ; *Oxidative Stress/drug effects ; Cell Line ; Cytoprotection/drug effects ; Epithelial Cells/drug effects/metabolism ; },
abstract = {Increased oxidative stress is one of the critical pathologies inducing age-related macular degeneration (AMD), characterized by retinal pigment epithelial (RPE) cell damage and death. The unbalanced acetylation and deacetylation of histones have been implicated in AMD pathogenesis or hydrogen peroxide (H2O2)-induced cell damage. Therefore, strategies aimed at controlling the balance between acetylation and deacetylation may effectively protect RPE cells from oxidative damage. Artemisinin is an antimalarial lactone drug derived from Artemisia annua, with antioxidant activity known to modulate histone acetylation in the brain, but its effect on the retina is unknown. In this study, we aimed to investigate whether Artemisinin exerts a cytoprotective effect on oxidative stress-induced apoptosis in RPE cells by regulating histone acetylation. We hypothesized that Artemisinin confers cytoprotection toward H2O2-induced apoptosis in RPE cells through this mechanism. In the present study, we found that Artemisinin at a sub-clinic dosage of 20 μM inhibited the H2O2-induced cell viability decrease and B-cell lymphoma 2 (Bcl-2) protein level decrease and attenuated the H2O2-induced decrease in the histone H4 lysine (Lys) 8 acetylation [Acetyl-H4 (Lys 8)] level in the retinal RPE cell line D407. As expected, histone deacetylase inhibitor Trichostatin A at the concentration of 250 nM increased the Acetyl-H4 (Lys 8) level in D407 cells and attenuated the H2O2-induced cell viability decrease and apoptosis. Similar findings were obtained using adult RPE (ARPE)19 cells, another human RPE cell line, and primary human RPE cell cultures. In conclusion, these results confirmed our hypothesis and indicated that Artemisinin attenuated H2O2-induced apoptosis in apparent correlation with the increase in the Acetyl-H4 (Lys 8) level, which is associated with gene transcription and cell survival. By modulating histone acetylation, Artemisinin may restore the balance between acetylation and deacetylation and enhance the resistance and survival of RPE cells under oxidative stress. Our study provides novel mechanistic insights into the effect of Artemisinin on histone acetylation and apoptosis in RPE cells and supports the potential application of Artemisinin in the prevention and/or treatment of AMD.},
}
@article {pmid38675477,
year = {2024},
author = {Peterson, SL and Krishnan, A and Patel, D and Khanehzar, A and Lad, A and Shaughnessy, J and Ram, S and Callanan, D and Kunimoto, D and Genead, MA and Tolentino, MJ},
title = {PolySialic Acid Nanoparticles Actuate Complement-Factor-H-Mediated Inhibition of the Alternative Complement Pathway: A Safer Potential Therapy for Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {4},
pages = {},
pmid = {38675477},
issn = {1424-8247},
abstract = {The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization.},
}
@article {pmid38675441,
year = {2024},
author = {Krishnan, A and Callanan, DG and Sendra, VG and Lad, A and Christian, S and Earla, R and Khanehzar, A and Tolentino, AJ and Vailoces, VAS and Greene, MK and Scott, CJ and Kunimoto, DY and Hassan, TS and Genead, MA and Tolentino, MJ},
title = {Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {4},
pages = {},
pmid = {38675441},
issn = {1424-8247},
support = {Unrestricted grant from Aviceda Therapeutics//Aviceda Therapeutics/ ; },
abstract = {An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation.},
}
@article {pmid38675402,
year = {2024},
author = {Rusciano, D and Russo, C},
title = {The Therapeutic Trip of Melatonin Eye Drops: From the Ocular Surface to the Retina.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {4},
pages = {},
pmid = {38675402},
issn = {1424-8247},
abstract = {Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous topical administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts. Moreover, it provides data suggesting that the topical administration of melatonin as eye drops is a real possibility, utilizing nanotechnological formulations that could improve its solubility and permeation through the eye. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.},
}
@article {pmid38675131,
year = {2024},
author = {Aljundi, W and Daas, L and Suffo, S and Seitz, B and Abdin, AD},
title = {First-Year Real-Life Experience with Intravitreal Faricimab for Refractory Neovascular Age-Related Macular Degeneration.},
journal = {Pharmaceutics},
volume = {16},
number = {4},
pages = {},
pmid = {38675131},
issn = {1999-4923},
abstract = {Background: To evaluate the outcomes of intravitreal faricimab (IVF) for refractory neovascular age-related macular degeneration (nAMD) and investigate the impact of baseline optical coherence tomography, biomarkers for total IVF injections are needed. Methods: A retrospective analysis of 33 eyes of patients who completed one year (52 W) of treatment with IVF. The eyes received four IVF injections (6 mg/0.05 mL) as the upload phase. Thereafter, the treatment interval was extended to 8 or 12 weeks if disease activity was not recorded. The outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal fluid distribution. Results: A total of 33 eyes were included. CMT decreased significantly at 52 W (p < 0.01). BCVA and SFCT did not change significantly at 52 W (p > 0.05). The number of eyes with subretinal fluid decreased significantly at 52 W (p < 0.01). Complete fluid resolution was achieved in 20 eyes (60%). The total number of injections was significantly negatively correlated with the presence of hyperreflective dots at baseline (HRDs, p < 0.01) and SFCT at baseline (p < 0.01). Conclusions: IVF led to a significant reduction in CMT with stabilization of BCVA. The total number of injections was lower in eyes with HRDs and increased SFCT at baseline. This might provide clues regarding response to IVF for future studies.},
}
@article {pmid38674349,
year = {2024},
author = {Seo, JH and Lee, Y},
title = {Causal Associations of Glaucoma and Age-Related Macular Degeneration with Cataract: A Bidirectional Two-Sample Mendelian Randomisation Study.},
journal = {Genes},
volume = {15},
number = {4},
pages = {},
pmid = {38674349},
issn = {2073-4425},
support = {No. 2022R1C1C1002929//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Macular Degeneration/genetics/epidemiology ; *Mendelian Randomization Analysis ; *Cataract/genetics ; *Polymorphism, Single Nucleotide ; *Genome-Wide Association Study ; *Glaucoma/genetics ; Glaucoma, Open-Angle/genetics/epidemiology ; Genetic Predisposition to Disease ; Japan/epidemiology ; },
abstract = {Common age-related eye disorders include glaucoma, cataract, and age-related macular degeneration (AMD); however, little is known about their relationship with age. This study investigated the potential causal relationship between glaucoma and AMD with cataract using genetic data from multi-ethnic populations. Single-nucleotide polymorphisms (SNPs) associated with exposure to cataract were selected as instrumental variables (IVs) from genome-wide association studies using meta-analysis data from BioBank Japan and UK Biobank. A bidirectional two-sample Mendelian randomisation (MR) study was conducted to assess the causal estimates using inverse variance weighted, MR-Egger, and MR pleiotropy residual sum and outlier tests. SNPs with (p < 5.0 × 10[-8]) were selected as IVs for cataract, primary open-angle glaucoma, and AMD. We found no causal effects of cataract on glaucoma or AMD (all p > 0.05). Furthermore, there were no causal effects of AMD on cataract (odds ratio [OR] = 1.02, p = 0.400). However, glaucoma had a substantial causal effect on cataract (OR = 1.14, p = 0.020). Our study found no evidence for a causal relationship of cataract on glaucoma or AMD and a casual effect of AMD on cataract. Nonetheless, glaucoma demonstrates a causal link with cataract formation, indicating the need for future investigations of age-related eye diseases.},
}
@article {pmid38674173,
year = {2024},
author = {Parmar, UPS and Surico, PL and Singh, RB and Romano, F and Salati, C and Spadea, L and Musa, M and Gagliano, C and Mori, T and Zeppieri, M},
title = {Artificial Intelligence (AI) for Early Diagnosis of Retinal Diseases.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {4},
pages = {},
pmid = {38674173},
issn = {1648-9144},
mesh = {Humans ; *Artificial Intelligence ; *Early Diagnosis ; *Retinal Diseases/diagnosis ; Diabetic Retinopathy/diagnosis ; Machine Learning ; Deep Learning ; Macular Degeneration/diagnosis ; },
abstract = {Artificial intelligence (AI) has emerged as a transformative tool in the field of ophthalmology, revolutionizing disease diagnosis and management. This paper provides a comprehensive overview of AI applications in various retinal diseases, highlighting its potential to enhance screening efficiency, facilitate early diagnosis, and improve patient outcomes. Herein, we elucidate the fundamental concepts of AI, including machine learning (ML) and deep learning (DL), and their application in ophthalmology, underscoring the significance of AI-driven solutions in addressing the complexity and variability of retinal diseases. Furthermore, we delve into the specific applications of AI in retinal diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), Macular Neovascularization, retinopathy of prematurity (ROP), retinal vein occlusion (RVO), hypertensive retinopathy (HR), Retinitis Pigmentosa, Stargardt disease, best vitelliform macular dystrophy, and sickle cell retinopathy. We focus on the current landscape of AI technologies, including various AI models, their performance metrics, and clinical implications. Furthermore, we aim to address challenges and pitfalls associated with the integration of AI in clinical practice, including the "black box phenomenon", biases in data representation, and limitations in comprehensive patient assessment. In conclusion, this review emphasizes the collaborative role of AI alongside healthcare professionals, advocating for a synergistic approach to healthcare delivery. It highlights the importance of leveraging AI to augment, rather than replace, human expertise, thereby maximizing its potential to revolutionize healthcare delivery, mitigate healthcare disparities, and improve patient outcomes in the evolving landscape of medicine.},
}
@article {pmid38674018,
year = {2024},
author = {Fragiotta, S and Bassis, L and Abdolrahimzadeh, B and Marino, A and Sepe, M and Abdolrahimzadeh, S},
title = {Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents.},
journal = {International journal of molecular sciences},
volume = {25},
number = {8},
pages = {},
pmid = {38674018},
issn = {1422-0067},
mesh = {Humans ; *Macular Degeneration/drug therapy/metabolism ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Molecular Targeted Therapy/methods ; Vascular Endothelial Growth Factor A/metabolism/antagonists &amp; inhibitors ; Animals ; Neovascularization, Pathologic/drug therapy/metabolism ; },
abstract = {Long-lasting anti-vascular endothelial growth factor (anti-VEGF) agents have become an option to reduce treatment frequency, with ongoing research exploring optimal responses and safety profiles. This review delves into molecular targets, pharmacological aspects, and strategies for achieving effective and enduring disease control in neovascular age-related macular degeneration (AMD). The molecular pathways involved in macular neovascularization, including angiogenesis and arteriogenesis, are explored. VEGF, PlGF, Ang-1, and Ang-2 play crucial roles in regulating angiogenesis, influencing vessel growth, maturation, and stability. The complex interplay of these factors, along with growth factors like TGFβ and bFGF, contributes to the pathogenesis of neovascular membranes. Current anti-VEGF therapies, including bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab, are discussed with a focus on their pharmacokinetics and clinical applications. Strategies to achieve sustained disease control in AMD involve smaller molecules, increased drug dosages, and novel formulations. This narrative review provides a comprehensive overview of the molecular targets and pharmacological aspects of neovascular AMD treatment.},
}
@article {pmid38673745,
year = {2024},
author = {Brodzka, S and Baszyński, J and Rektor, K and Hołderna-Bona, K and Stanek, E and Kurhaluk, N and Tkaczenko, H and Malukiewicz, G and Woźniak, A and Kamiński, P},
title = {The Role of Glutathione in Age-Related Macular Degeneration (AMD).},
journal = {International journal of molecular sciences},
volume = {25},
number = {8},
pages = {},
pmid = {38673745},
issn = {1422-0067},
mesh = {Animals ; Humans ; *Glutathione/metabolism ; Glutathione Transferase/metabolism/genetics ; *Macular Degeneration/metabolism/genetics/pathology ; Oxidative Stress ; },
abstract = {Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet-progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase mu-1 (GSTM1) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye.},
}
@article {pmid38673690,
year = {2024},
author = {Ando, M and Kato, A and Kimura, M and Ogura, S and Kuwayama, S and Kominami, A and Kuwayama, S and Obayashi, T and Ando, R and Monoe, T and Morita, H and Yasukawa, T},
title = {Effects of Combination Therapy with Intravitreal Ranibizumab and Tissue Plasminogen Activator for Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {8},
pages = {},
pmid = {38673690},
issn = {2077-0383},
abstract = {Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm[3] to 9.6 mm[3], from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.},
}
@article {pmid38672747,
year = {2024},
author = {Machida, A and Oishi, A and Ikeda, J and Kurihara, J and Yoneda, A and Tsuiki, E and Hirata, Y and Murakami, R and Kitaoka, T},
title = {Factors Associated with Success of Switching to Faricimab for Neovascular Age-Related Macular Degeneration Refractory to Intravitreal Aflibercept.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {38672747},
issn = {2075-1729},
support = {22K09793//Japan Society for the Promotion of Science/ ; },
abstract = {We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals.},
}
@article {pmid38672162,
year = {2024},
author = {Yoon, BW and Lee, Y and Seo, JH},
title = {Potential Causal Association between C-Reactive Protein Levels in Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.},
journal = {Biomedicines},
volume = {12},
number = {4},
pages = {},
pmid = {38672162},
issn = {2227-9059},
support = {2022R1C1C1002929//National Research Foundation of Korea/ ; 2022//Chung-Ang University Research Grant/ ; },
abstract = {Researchers have proposed a possible correlation between age-related macular degeneration (AMD) and inflammation or C-reactive protein (CRP) levels. We investigated the potential causal relationship between CRP levels and AMD. Single-nucleotide polymorphisms (SNPs) associated with CRP exposure were selected as the instrumental variables (IVs) with significance (p < 5 × 10[-8]) from the genome-wide association study (GWAS) meta-analysis data of Biobank Japan and the UK Biobank. GWAS data for AMD were obtained from 11 International AMD Genomics Consortium studies. An evaluation of causal estimates, utilizing the inverse-variance-weighted (IVW), weighted-median, MR-Egger, MR-Pleiotropy-Residual-Sum, and Outlier tests, was conducted in a two-sample Mendelian randomization (MR) study. We observed significant causal associations between CRP levels and AMD (odds ratio [OR] = 1.13, 95% CI = [1.02-1.24], and p = 0.014 in IVW; OR = 1.18, 95% CI = [1.00-1.38], and p = 0.044 in weight median; OR = 1.31, 95% CI = [1.13-1.52], and p < 0.001 in MR-Egger). The causal relationship between CRP and AMD warrants further research to address the significance of inflammation as a risk factor for AMD.},
}
@article {pmid38672083,
year = {2024},
author = {Lin, HT and Zheng, CM and Tsai, CH and Chen, CL and Chou, YC and Zheng, JQ and Lin, YF and Lin, CW and Chen, YC and Sun, CA and Chen, JT},
title = {The Association between Diabetic Retinopathy and Macular Degeneration: A Nationwide Population-Based Study.},
journal = {Biomedicines},
volume = {12},
number = {4},
pages = {},
pmid = {38672083},
issn = {2227-9059},
abstract = {OBJECTIVE: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan.<br><br>METHODS: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000-2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan-Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions.<br><br>RESULTS: Kaplan-Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10-3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04-3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08-4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51-6.14).<br><br>CONCLUSION: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.},
}
@article {pmid38671722,
year = {2024},
author = {Alenezi, A and Alhamad, H and Brindhaban, A and Amizadeh, Y and Jodeiri, A and Danishvar, S},
title = {Enhancing Readability and Detection of Age-Related Macular Degeneration Using Optical Coherence Tomography Imaging: An AI Approach.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {4},
pages = {},
pmid = {38671722},
issn = {2306-5354},
abstract = {Artificial intelligence has been used effectively in medical diagnosis. The objective of this project is to examine the application of a collective AI model using weighted fusion of predicted probabilities from different AI architectures to diagnose various retinal conditions based on optical coherence tomography (OCT). A publicly available Noor dataset, comprising 16,822, images from 554 retinal OCT scans of 441 patients, was used to predict a diverse spectrum of age-related macular degeneration (AMD) stages: normal, drusen, or choroidal neovascularization. These predictions were compared with predictions from ResNet, EfficientNet, and Attention models, respectively, using precision, recall, F1 score, and confusion matric and receiver operating characteristics curves. Our collective model demonstrated superior accuracy in classifying AMD compared to individual ResNet, EfficientNet, and Attention models, showcasing the effectiveness of using trainable weights in the ensemble fusion process, where these weights dynamically adapt during training rather than being fixed values. Specifically, our ensemble model achieved an accuracy of 91.88%, precision of 92.54%, recall of 92.01%, and F1 score of 92.03%, outperforming individual models. Our model also highlights the refinement process undertaken through a thorough examination of initially misclassified cases, leading to significant improvements in the model's accuracy rate to 97%. This study also underscores the potential of AI as a valuable tool in ophthalmology. The proposed ensemble model, combining different mechanisms highlights the benefits of model fusion for complex medical image analysis.},
}
@article {pmid38671486,
year = {2024},
author = {Touma, S and Hammou, BA and Antaki, F and Boucher, MC and Duval, R},
title = {Comparing code-free deep learning models to expert-designed models for detecting retinal diseases from optical coherence tomography.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {37},
pmid = {38671486},
issn = {2056-9920},
support = {Fonds de recherche en ophtalmologie de l'Universit&#xe9; de Montr&#xe9;al//Fonds de recherche en ophtalmologie de l'Universit&#xe9; de Montr&#xe9;al/ ; },
abstract = {BACKGROUND: Code-free deep learning (CFDL) is a novel tool in artificial intelligence (AI). This study directly compared the discriminative performance of CFDL models designed by ophthalmologists without coding experience against bespoke models designed by AI experts in detecting retinal pathologies from optical coherence tomography (OCT) videos and fovea-centered images.<br><br>METHODS: Using the same internal dataset of 1,173 OCT macular videos and fovea-centered images, model development was performed simultaneously but independently by an ophthalmology resident (CFDL models) and a postdoctoral researcher with expertise in AI (bespoke models). We designed a multi-class model to categorize video and fovea-centered images into five labels: normal retina, macular hole, epiretinal membrane, wet age-related macular degeneration and diabetic macular edema. We qualitatively compared point estimates of the performance metrics of the CFDL and bespoke models.<br><br>RESULTS: For videos, the CFDL model demonstrated excellent discriminative performance, even outperforming the bespoke models for some metrics: area under the precision-recall curve was 0.984 (vs. 0.901), precision and sensitivity were both 94.1% (vs. 94.2%) and accuracy was 94.1% (vs. 96.7%). The fovea-centered CFDL model overall performed better than video-based model and was as accurate as the best bespoke model.<br><br>CONCLUSION: This comparative study demonstrated that code-free models created by clinicians without coding expertise perform as accurately as expert-designed bespoke models at classifying various retinal pathologies from OCT videos and images. CFDL represents a step forward towards the democratization of AI in medicine, although its numerous limitations must be carefully addressed to ensure its effective application in healthcare.},
}
@article {pmid38671028,
year = {2024},
author = {Eckardt, F and Lorger, A and Hafner, M and Klaas, JE and Schworm, B and Kreutzer, TC and Priglinger, SG and Siedlecki, J},
title = {Retinal and choroidal efficacy of switching treatment to faricimab in recalcitrant neovascular age related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {9600},
pmid = {38671028},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; Aged ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Choroid/drug effects/diagnostic imaging/pathology ; Aged, 80 and over ; Treatment Outcome ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; Retina/pathology/drug effects/diagnostic imaging ; Intravitreal Injections ; Macular Degeneration/drug therapy/pathology ; Tomography, Optical Coherence ; Visual Acuity/drug effects ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Drug Substitution ; },
abstract = {Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.},
}
@article {pmid38670262,
year = {2024},
author = {Abbasgholizadeh, R and Habibi, A and Emamverdi, M and Ashrafkhorasani, M and London, N and Sinai, MJ and Sinai, EC and Sadda, SR},
title = {Comparison of Blue-Light Autofluorescence and Ultrawidefield Green-Light Autofluorescence for Assessing Geographic Atrophy.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {10},
pages = {987-993},
doi = {10.1016/j.oret.2024.04.017},
pmid = {38670262},
issn = {2468-6530},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; Prospective Studies ; Female ; Male ; *Fluorescein Angiography/methods ; Aged ; *Fundus Oculi ; *Tomography, Optical Coherence/methods ; Aged, 80 and over ; Reproducibility of Results ; Middle Aged ; Visual Acuity ; Retinal Pigment Epithelium/pathology ; },
abstract = {PURPOSE: The goal of this study was to evaluate and compare the intermodality and interreader agreement of manual and semiautomated geographic atrophy (GA) area measurements in eyes with GA due to age-related macular degeneration (AMD) using conventional blue-light fundus autofluorescence (FAF) and ultrawidefield (UWF) green-light FAF systems.<br><br>DESIGN: Prospective Cohort Study.<br><br>SUBJECTS: Seventy-two eyes of 50 patients with a diagnosis of advanced nonneovascular AMD with GA.<br><br>METHODS: Fundus autofluorescence images of eyes with GA were obtained during a single visit using both the Spectralis HRA&#xa0;+ OCT2 device and the Optos California device. The area of the GA lesion(s) was segmented and quantified (mm[2]) with a fully manual approach where the lesions were outlined using Optos Advance and Heidelberg Eye Explorer (HEYEX) software. In addition, for the Heidelberg blue FAF images, GA lesions were also measured using the instrument's semiautomated software (Region Finder 2.6.4). For comparison between modalities/grading method, the mean values of the 2 graders were used. Intraclass correlation coefficients were computed to judge the agreement between graders.<br><br>RESULTS: Seventy-two eyes of 50 patients were included in this study. There was nearly perfect agreement between graders for the measurement of GA area for all 3 modalities (intraclass correlation coefficient: 0.996 for manual Optos Advance, 0.996 for manual Heidelberg HEYEX, and 0.995 for Heidelberg Region Finder). The measurement of GA area was strongly correlated between modalities, with Spearman correlation coefficients of 0.985 (P < 0.001) between manual Heidelberg and manual Optos, 0.991 (P < 0.001) for Region Finder versus manual Heidelberg, and 0.985 (P < 0.001) for Region Finder versus manual Optos. The absolute mean area differences between the Heidelberg manual versus Region Finder, manual Optos versus Region Finder, and manual Optos versus manual Heidelberg were 1.61 mm[2] (P < 0.001), 0.90 mm[2] (P < 0.006), and 0.71 mm[2] (P&#xa0;<&#xa0;0.001), respectively.<br><br>CONCLUSIONS: We observed excellent interreader agreement for measurement of GA using either 30-degree blue-light FAF or UWF green-light FAF, establishing the reliability of UWF imaging for macular GA assessment. Although the absolute measurements between devices were strongly correlated, they differed significantly, highlighting the importance of using the same device for a given patient for the duration of a study.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38669379,
year = {2024},
author = {Qi, Y and Li, C and Ye, S and Zhang, Z and Li, S and Zhang, L},
title = {Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs.},
journal = {Medicine},
volume = {103},
number = {17},
pages = {e37937},
pmid = {38669379},
issn = {1536-5964},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Cornea/pathology/drug effects ; Endothelium, Corneal/drug effects/pathology ; *Intravitreal Injections ; Macular Degeneration/drug therapy ; *Macular Edema/drug therapy ; Prospective Studies ; *Ranibizumab/administration &amp; dosage ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Retinal Vein Occlusion/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P < .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P < .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.},
}
@article {pmid38667772,
year = {2024},
author = {Lixi, F and Vitiello, L and Giannaccare, G},
title = {Marine Natural Products Rescuing the Eye: A Narrative Review.},
journal = {Marine drugs},
volume = {22},
number = {4},
pages = {},
pmid = {38667772},
issn = {1660-3397},
mesh = {Humans ; *Biological Products/pharmacology/therapeutic use ; *Aquatic Organisms ; Animals ; *Eye Diseases/drug therapy ; Antioxidants/pharmacology/therapeutic use ; },
abstract = {Different degrees of visual impairment lead to a decrease in patient wellbeing, which has an adverse effect on many facets of social and professional life. Eye disorders can affect several parts of the eye, most notably the retina and the cornea, and the impacted areas might share a common form of cellular damage or dysfunction (such as inflammation, oxidative stress and neuronal degeneration). Considering that marine organisms inhabit a broad variety of marine habitats, they display a great degree of chemical diversity. As a result, molecules with a marine origin are receiving more and more attention in the hopes of developing novel therapeutic approaches. For instance, fucoxanthin has been demonstrated to be effective in protecting the retina against photo-induced damage, while largazole, astaxanthin and spirulina have all shown antioxidant, anti-inflammatory and antiapoptotic activities that can be useful for the management of several ocular diseases, such as age-related macular degeneration and ocular surface disorders. The aim of this review is to analyze the scientific literature relating to the therapeutic effects on the eye of the main natural marine products, focusing on their mechanism of action and potential clinical uses for the management of ocular diseases.},
}
@article {pmid38665911,
year = {2024},
author = {Khan, AM and Steffensen, MA and Paskeviciute, E and Abduljabar, AB and Sørensen, TL and Vorum, H and Nissen, MH and Honoré, B},
title = {Neuroretinal degeneration in a mouse model of systemic chronic immune activation observed by proteomics.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1374617},
pmid = {38665911},
issn = {1664-3224},
mesh = {Animals ; Mice ; *Proteomics/methods ; *Disease Models, Animal ; *Retinal Degeneration/immunology/metabolism/pathology ; *Lymphocytic choriomeningitis virus/immunology ; Mice, Inbred C57BL ; Lymphocytic Choriomeningitis/immunology/virology ; Tandem Mass Spectrometry ; Proteome ; Retina/immunology/metabolism/pathology ; Chromatography, Liquid ; Choroid/immunology/pathology/metabolism ; },
abstract = {Blindness or vision loss due to neuroretinal and photoreceptor degeneration affects millions of individuals worldwide. In numerous neurodegenerative diseases, including age-related macular degeneration, dysregulated immune response-mediated retinal degeneration has been found to play a critical role in the disease pathogenesis. To better understand the pathogenic mechanisms underlying the retinal degeneration, we used a mouse model of systemic immune activation where we infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13. Here, we evaluated the effects of LCMV infection and present a comprehensive discovery-based proteomic investigation using tandem mass tag (TMT) labeling and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Changes in protein regulation in the posterior part of the eye, neuroretina, and RPE/choroid were compared to those in the spleen as a secondary lymphoid organ and to the kidney as a non-lymphoid but encapsulated organ at 1, 8, and 28 weeks of infection. Using bioinformatic tools, we found several proteins responsible for maintaining normal tissue homeostasis to be differentially regulated in the neuroretina and the RPE/choroid during the degenerative process. Additionally, in the organs we observed, several important protein pathways contributing to cellular homeostasis and tissue development were perturbed and associated with LCMV-mediated inflammation, promoting disease progression. Our findings suggest that the response to a systemic chronic infection differs between the neuroretina and the RPE/choroid, and the processes induced by chronic systemic infection in the RPE/choroid are not unlike those induced in non-immune-privileged organs such as the kidney and spleen. Overall, our data provide detailed insight into several molecular mechanisms of neuroretinal degeneration and highlight various novel protein pathways that further suggest that the posterior part of the eye is not an isolated immunological entity despite the existence of neuroretinal immune privilege.},
}
@article {pmid38664229,
year = {2024},
author = {Zhang, X and Fu, Q and Cai, Y and Li, X and Chen, L and Jiang, Y and Chen, Y},
title = {Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study.},
journal = {Human molecular genetics},
volume = {33},
number = {14},
pages = {1241-1249},
doi = {10.1093/hmg/ddae041},
pmid = {38664229},
issn = {1460-2083},
support = {82271050//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Cytokines/blood/genetics ; *Cataract/blood/genetics ; *Macular Degeneration/genetics/blood ; *Glaucoma/genetics/blood ; *Genetic Predisposition to Disease ; Risk Factors ; Polymorphism, Single Nucleotide ; Male ; Female ; Eye Diseases/genetics/blood ; },
abstract = {PURPOSE: Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases.<br><br>PATIENTS AND METHODS: Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran's Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis.<br><br>RESULTS: Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-&#x3b2;, 1.099 [95%CI, 1.037-1.166], P&#x2009;=&#x2009;0.002; SCF, 1.155 [95%CI, 1.015-1.315], P&#x2009;=&#x2009;0.029; MCP-1, 1.103 [95%CI, 1.012-1.202], P&#x2009;=&#x2009;0.026; IL-10, 1.102 [95%CI, 1.012-1.200], P&#x2009;=&#x2009;0.025; eotaxin, 1.086 [95%CI, 1.002-1.176], P&#x2009;=&#x2009;0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894-0.999], P&#x2009;=&#x2009;0.047; IL1ra, 0.886 [95%CI, 0.809-0.969], P&#x2009;=&#x2009;0.008; IL-1&#x3b2;, 0.866 [95%CI, 0.762-0.983], P&#x2009;=&#x2009;0.027; IL-9, 0.908 [95%CI, 0.841-0.980], P&#x2009;=&#x2009;0.014; IL2ra, 1.065 [95%CI, 1.004-1.130], P&#x2009;=&#x2009;0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009-1.077], P&#x2009;=&#x2009;0.011; IL-16, 1.032 [95%CI, 1.001-1.064], P&#x2009;=&#x2009;0.046; IL1ra, 0.942 [95%CI, 0.887-0.999], P&#x2009;=&#x2009;0.047; FGF-basic, 1.144 [95%CI, 1.052-1.244], P&#x2009;=&#x2009;0.002). Furthermore, sensitivity analysis results supported the above associations.<br><br>CONCLUSION: This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.},
}
@article {pmid38664003,
year = {2024},
author = {Chen, J and Zhu, Y and Li, Z and Zhuo, X and Zhang, S and Zhuo, Y},
title = {Age-period-cohort analysis of the global burden of visual impairment according to major causes: an analysis of the Global Burden of Disease Study 2019.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {11},
pages = {1605-1612},
doi = {10.1136/bjo-2023-324086},
pmid = {38664003},
issn = {1468-2079},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Cataract/epidemiology/complications ; Prevalence ; *Glaucoma/epidemiology/physiopathology/complications ; Aged, 80 and over ; *Global Burden of Disease ; Adult ; Macular Degeneration/epidemiology/complications ; Persons with Visual Disabilities/statistics &amp; numerical data ; Age Distribution ; Visual Acuity/physiology ; Global Health ; Vision Disorders/epidemiology/physiopathology ; Cohort Studies ; Vision, Low/epidemiology ; Young Adult ; Adolescent ; },
abstract = {BACKGROUND: Cataract, glaucoma and age-related macular degeneration (AMD) are major causes of visual impairment. As these are age-related conditions, the prevalence of associated visual impairment is anticipated to increase as the population ages. However, age-period-cohort effects on the disease burden have not been investigated.<br><br>METHODS: This was a population-based study using aggregated data from the Global Burden of Disease Study 2019. Age-period-cohort analysis was conducted using age-standardised prevalence rates (ASPRs) of visual impairment caused by cataract, glaucoma and AMD as disease burden indicator.<br><br>RESULTS: In 2019, the estimated global ASPRs of visual impairment due to cataract, glaucoma and AMD were 1207.9, 94.7 and 96.8 per 100&#x2009;000 people, respectively. Between 1990 and 2019, the global visual impairment ASPRs for glaucoma and AMD declined by 15.4% and 2.0%, respectively, whereas that for cataract increased by 5.0%. Wide heterogeneity was observed in age-period-cohort effects on ASPRs across different Sociodemographic Index (SDI) regions. Low-middle SDI regions had the largest ASPR reductions for all three eye diseases and showed improvement in both period and cohort effects. In contrast, in high-middle SDI regions, visual impairment ASPRs significantly increased during the study period with unfavourable patterns.<br><br>CONCLUSIONS: The wide heterogeneity in age-period-cohort effects reflects different stages of societal transition and vision health. The unfavourable trends in age-period-cohort effects on disease prevalence identified in specific groups provide key information that may be used to identify priority groups in need of treatment and prevention.},
}
@article {pmid38663763,
year = {2024},
author = {Aschner, M and Skalny, AV and Paoliello, MMB and Tinkova, MN and Martins, AC and Santamaria, A and Lee, E and Rocha, JBT and Farsky, SHP and Tinkov, AA},
title = {Retinal toxicity of heavy metals and its involvement in retinal pathology.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {188},
number = {},
pages = {114685},
pmid = {38663763},
issn = {1873-6351},
support = {R01 ES010563/ES/NIEHS NIH HHS/United States ; R01 ES031282/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Retina/drug effects/pathology/metabolism ; *Metals, Heavy/toxicity ; Animals ; Oxidative Stress/drug effects ; Macular Degeneration/chemically induced ; },
abstract = {The objective of the present review is to discuss epidemiological evidence demonstrating the association between toxic metal (Cd, Pb, Hg, As, Sn, Ti, Tl) exposure and retinal pathology, along with the potential underlying molecular mechanisms. Epidemiological studies demonstrate that Cd, and to a lesser extent Pb exposure, are associated with age-related macular degeneration (AMD), while the existing evidence on the levels of these metals in patients with diabetic retinopathy is scarce. Epidemiological data on the association between other toxic metals and metalloids including mercury (Hg) and arsenic (As), are limited. Clinical reports and laboratory in vivo studies have shown structural alterations in different layers of retina following metal exposure. Examination of retina samples demonstrate that toxic metals can accumulate in the retina, and the rate of accumulation appears to increase with age. Experimental studies in vivo and in vitro studies in APRE-19 and D407 cells demonstrate that toxic metal exposure may cause retinal damage through oxidative stress, apoptosis, DNA damage, mitochondrial dysfunction, endoplasmic reticulum stress, impaired retinogenesis, and retinal inflammation. However, further epidemiological as well as laboratory studies are required for understanding the underlying molecular mechanisms and identifying of the potential therapeutic targets and estimation of the dose-response effects.},
}
@article {pmid38662523,
year = {2024},
author = {Swain, TA and McGwin, G and Girkin, CA and Owsley, C},
title = {Telemedicine Screening for Eye Disorders in Federally Qualified Health Centers: Relationship to Vision-Targeted Health-Related Quality of Life.},
journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association},
volume = {30},
number = {7},
pages = {e2080-e2086},
pmid = {38662523},
issn = {1556-3669},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Male ; *Quality of Life ; Female ; *Telemedicine ; Middle Aged ; Alabama ; Aged ; Eye Diseases/diagnosis ; Safety-net Providers ; Visual Acuity ; Vision Screening/methods ; Diabetic Retinopathy/diagnosis ; Socioeconomic Factors ; Glaucoma/diagnosis ; Sociodemographic Factors ; Vision Disorders/diagnosis/epidemiology ; Adult ; Surveys and Questionnaires ; },
abstract = {Introduction: Federally Qualified Health Centers (FQHCs) play a crucial role as safety-net primary health care clinics in the United States, serving medically underserved areas and populations. However, eye services are rarely offered at FQHCs. We examined how telemedicine-generated ocular diagnoses impacted vision-targeted health-related quality of life at FQHCs in rural Alabama. Methods: We focused on patients who are at risk for glaucoma. Both visual function and retinal imaging were assessed. The telemedicine vision screening protocol performed by a remote ophthalmologist evaluated eyes for glaucoma, diabetic retinopathy, cataract, age-related macular degeneration, and a measurement of habitual visual acuity. The National Eye Institute Visual Function Questionnaire-9 (VFQ-9) was administered. Results: Using stepwise regression, the best-fitting model for predicting VFQ-9 scores incorporated visual acuity 20/40 or worse, a diabetic retinopathy diagnosis, and sociodemographic variables (gender, transportation, insurance type/status, and employment status). Conclusion: Vision-targeted, health-related quality of life in our FQHC settings was related to the visual acuity impairment and the diagnosis of diabetic retinopathy but was also influenced by a variety of sociodemographic factors.},
}
@article {pmid38662399,
year = {2024},
author = {Hogg, RE and Sivaprasad, S and Wickens, R and O'Connor, S and Gidman, E and Ward, E and Treanor, C and Peto, T and Burton, BJL and Knox, P and Lotery, AJ and Donnelly, M and Rogers, CA and Reeves, BC},
title = {Home-Monitoring Vision Tests to Detect Active Neovascular Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {142},
number = {6},
pages = {512-520},
pmid = {38662399},
issn = {2168-6173},
mesh = {Humans ; Male ; Female ; Aged ; *Visual Acuity/physiology ; *Vision Tests/instrumentation ; *Wet Macular Degeneration/diagnosis/drug therapy/physiopathology ; Aged, 80 and over ; ROC Curve ; Reproducibility of Results ; Mobile Applications ; Follow-Up Studies ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Tomography, Optical Coherence ; },
abstract = {IMPORTANCE: Most neovascular age-related macular degeneration (nAMD) treatments involve long-term follow-up of disease activity. Home-monitoring would reduce the burden on patients and their caregivers and release clinic capacity.<br><br>OBJECTIVE: To evaluate 3 vision home-monitoring tests for patients to use to detect active nAMD compared with diagnosing active nAMD at hospital follow-up during the after-treatment monitoring phase.<br><br>This was a diagnostic test accuracy study wherein the reference standard was detection of active nAMD by an ophthalmologist at hospital follow-up. The 3 home-monitoring tests evaluated included the following: (1) the KeepSight Journal (KSJ [International Macular and Retinal Foundation]), which contains paper-based near-vision tests presented as word puzzles, (2) the MyVisionTrack (mVT [Genentech]) vision-monitoring mobile app, viewed on an Apple mobile operating system-based device, and (3) the MultiBit (MBT [Visumetrics]) app, viewed on an Apple mobile operating system-based device. Participants were asked to test weekly; mVT and MBT scores were transmitted automatically, and KSJ scores were returned to the research office every 6 months. Raw scores between hospital follow-ups were summarized as averages. Patients were recruited from 6 UK hospital eye clinics and were 50 years and older with at least 1 eye first treated for active nAMD for at least 6 months or longer to a maximum of 42 months before approach. Participants were stratified by time since starting treatment. Study data were analyzed from May to September 2021.<br><br>EXPOSURES: The KSJ, mVT, and MBT were compared with the reference standard (in-hospital ophthalmologist examination).<br><br>MAIN OUTCOMES AND MEASURES: Estimated area under receiver operating characteristic curve (AUROC). The study had 90% power to detect a difference of 0.06, or 80% power to detect a difference of 0.05, if the AUROC for 2 tests was 0.75.<br><br>RESULTS: A total of 297 patients (mean [SD] age, 74.9 [6.6] years; 174 female [58.6%]) were included in the study. At least 1 hospital follow-up was available for 312 study eyes in 259 participants (1549 complete visits). Median (IQR) home-monitoring testing frequency was 3 (1-4) times per month. Estimated AUROC was less than 0.6 for all home-monitoring tests, and only the KSJ summary score was associated with lesion activity (odds ratio,&#x2009;3.48; 95% CI, 1.09-11.13; P&#x2009;=&#x2009;.04).<br><br>CONCLUSIONS AND RELEVANCE: Results suggest that no home-monitoring vision test evaluated provided satisfactory diagnostic accuracy to identify active nAMD diagnosed in hospital eye service follow-up clinics. Implementing any of these evaluated tests, with ophthalmologists only reviewing test positives, would mean most active lesions were missed, risking unnecessary sight loss.},
}
@article {pmid38662397,
year = {2024},
author = {Blinder, KJ},
title = {More Homework for Patients With Macular Degeneration?.},
journal = {JAMA ophthalmology},
volume = {142},
number = {6},
pages = {520-521},
doi = {10.1001/jamaophthalmol.2024.1050},
pmid = {38662397},
issn = {2168-6173},
mesh = {Humans ; *Macular Degeneration/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Visual Acuity/physiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
}
@article {pmid38660183,
year = {2024},
author = {Jacaruso, L},
title = {Insights into the nutritional prevention of macular degeneration based on a comparative topic modeling approach.},
journal = {PeerJ. Computer science},
volume = {10},
number = {},
pages = {e1940},
pmid = {38660183},
issn = {2376-5992},
abstract = {Topic modeling and text mining are subsets of natural language processing (NLP) with relevance for conducting meta-analysis (MA) and systematic review (SR). For evidence synthesis, the above NLP methods are conventionally used for topic-specific literature searches or extracting values from reports to automate essential phases of SR and MA. Instead, this work proposes a comparative topic modeling approach to analyze reports of contradictory results on the same general research question. Specifically, the objective is to identify topics exhibiting distinct associations with significant results for an outcome of interest by ranking them according to their proportional occurrence in (and consistency of distribution across) reports of significant effects. Macular degeneration (MD) is a disease that affects millions of people annually, causing vision loss. Augmenting evidence synthesis to provide insight into MD prevention is therefore of central interest in this article. The proposed method was tested on broad-scope studies addressing whether supplemental nutritional compounds significantly benefit macular degeneration. Six compounds were identified as having a particular association with reports of significant results for benefiting MD. Four of these were further supported in terms of effectiveness upon conducting a follow-up literature search for validation (omega-3 fatty acids, copper, zeaxanthin, and nitrates). The two not supported by the follow-up literature search (niacin and molybdenum) also had scores in the lowest range under the proposed scoring system. Results therefore suggest that the proposed method's score for a given topic may be a viable proxy for its degree of association with the outcome of interest, and can be helpful in the systematic search for potentially causal relationships. Further, the compounds identified by the proposed method were not simultaneously captured as salient topics by state-of-the-art topic models that leverage document and word embeddings (Top2Vec) and transformer models (BERTopic). These results underpin the proposed method's potential to add specificity in understanding effects from broad-scope reports, elucidate topics of interest for future research, and guide evidence synthesis in a scalable way. All of this is accomplished while yielding valuable and actionable insights into the prevention of MD.},
}
@article {pmid38659843,
year = {2024},
author = {Bhuckory, MB and Monkongpitukkul, N and Shin, A and Goldstein, AK and Jensen, N and Shah, SV and Pham-Howard, D and Butt, E and Dalal, R and Galambos, L and Mathieson, K and Kamins, T and Palanker, D},
title = {Enhancing Prosthetic Vision by Upgrade of a Subretinal Photovoltaic Implant in situ.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38659843},
issn = {2692-8205},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; R01 EY035227/EY/NEI NIH HHS/United States ; },
abstract = {In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100μm pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22μm pixels increased the grating acuity from the 100μm capability of PRIMA implants to 28μm, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.},
}
@article {pmid38657840,
year = {2024},
author = {Agrón, E and Domalpally, A and Chen, Q and Lu, Z and Chew, EY and Keenan, TDL and , },
title = {An Updated Simplified Severity Scale for Age-Related Macular Degeneration Incorporating Reticular Pseudodrusen: Age-Related Eye Disease Study Report Number 42.},
journal = {Ophthalmology},
volume = {131},
number = {10},
pages = {1164-1174},
pmid = {38657840},
issn = {1549-4713},
support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; ZIA EY000546/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Retinal Drusen/diagnosis ; Female ; Male ; *Disease Progression ; Aged ; *Severity of Illness Index ; *Geographic Atrophy/diagnosis ; Aged, 80 and over ; Wet Macular Degeneration/diagnosis ; Middle Aged ; Follow-Up Studies ; Macular Degeneration/diagnosis ; Visual Acuity/physiology ; },
abstract = {PURPOSE: To update the Age-Related Eye Disease Study (AREDS) simplified severity scale for risk of late age-related macular degeneration (AMD), including incorporation of reticular pseudodrusen (RPD), and to perform external validation on the Age-Related Eye Disease Study 2 (AREDS2).<br><br>DESIGN: Post hoc analysis of 2 clinical trial cohorts: AREDS and AREDS2.<br><br>PARTICIPANTS: Participants with no late AMD in either eye at baseline in AREDS (n&#xa0;= 2719) and AREDS2 (n&#xa0;= 1472).<br><br>METHODS: Five-year rates of progression to late AMD were calculated according to levels 0 to 4 on the simplified severity scale after 2 updates: (1) noncentral geographic atrophy (GA) considered part of the outcome, rather than a risk feature, and (2) scale separation according to RPD status (determined by validated deep learning grading of color fundus photographs).<br><br>MAIN OUTCOME MEASURES: Five-year rate of progression to late AMD (defined as neovascular AMD or any GA).<br><br>RESULTS: In the AREDS, after the first scale update, the 5-year rates of progression to late AMD for levels 0 to 4 were 0.3%, 4.5%, 12.9%, 32.2%, and 55.6%, respectively. As the final simplified severity scale, the 5-year progression rates for levels 0 to 4 were 0.3%, 4.3%, 11.6%, 26.7%, and 50.0%, respectively, for participants without RPD at baseline and 2.8%, 8.0%, 29.0%, 58.7%, and 72.2%, respectively, for participants with RPD at baseline. In external validation on the AREDS2, for levels 2 to 4, the progression rates were similar: 15.0%, 27.7%, and 45.7% (RPD absent) and 26.2%, 46.0%, and 73.0% (RPD present), respectively.<br><br>CONCLUSIONS: The AREDS AMD simplified severity scale has been modernized with 2 important updates. The new scale for individuals without RPD has 5-year progression rates of approximately 0.5%, 4%, 12%, 25%, and 50%, such that the rates on the original scale remain accurate. The new scale for individuals with RPD has 5-year progression rates of approximately 3%, 8%, 30%, 60%, and 70%, that is, approximately double for most levels. This scale fits updated definitions of late AMD, has increased prognostic accuracy, seems generalizable to similar populations, but remains simple for broad risk categorization.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38657834,
year = {2024},
author = {Sun, Y and Li, F and Liu, Y and Qiao, D and Yao, X and Liu, GS and Li, D and Xiao, C and Wang, T and Chi, W},
title = {Targeting inflammasomes and pyroptosis in retinal diseases-molecular mechanisms and future perspectives.},
journal = {Progress in retinal and eye research},
volume = {101},
number = {},
pages = {101263},
doi = {10.1016/j.preteyeres.2024.101263},
pmid = {38657834},
issn = {1873-1635},
mesh = {Humans ; *Pyroptosis/physiology ; *Inflammasomes/physiology/metabolism ; *Retinal Diseases/metabolism/drug therapy ; Animals ; *Immunity, Innate/physiology ; },
abstract = {Retinal diseases encompass various conditions associated with sight-threatening immune responses and are leading causes of blindness worldwide. These diseases include age-related macular degeneration, diabetic retinopathy, glaucoma and uveitis. Emerging evidence underscores the vital role of the innate immune response in retinal diseases, beyond the previously emphasized T-cell-driven processes of the adaptive immune system. In particular, pyroptosis, a newly discovered programmed cell death process involving inflammasome formation, has been implicated in the loss of membrane integrity and the release of inflammatory cytokines. Several disease-relevant animal models have provided evidence that the formation of inflammasomes and the induction of pyroptosis in innate immune cells contribute to inflammation in various retinal diseases. In this review article, we summarize current knowledge about the innate immune system and pyroptosis in retinal diseases. We also provide insights into translational targeting approaches, including novel drugs countering pyroptosis, to improve the diagnosis and treatment of retinal diseases.},
}
@article {pmid38657717,
year = {2024},
author = {Zhong, C and Shi, Z and Binzel, DW and Jin, K and Li, X and Guo, P and Li, SK},
title = {Posterior eye delivery of angiogenesis-inhibiting RNA nanoparticles via subconjunctival injection.},
journal = {International journal of pharmaceutics},
volume = {657},
number = {},
pages = {124151},
pmid = {38657717},
issn = {1873-3476},
support = {P30 CA016058/CA/NCI NIH HHS/United States ; R01 EY031452/EY/NEI NIH HHS/United States ; UL1 TR001425/TR/NCATS NIH HHS/United States ; },
mesh = {Animals ; *Nanoparticles/chemistry ; *Angiogenesis Inhibitors/administration &amp; dosage/pharmacology/chemistry ; *Vascular Endothelial Growth Factor A ; *RNA/administration &amp; dosage ; Aptamers, Nucleotide/administration &amp; dosage/chemistry ; Humans ; Angiopoietin-2 ; Male ; Mice ; Conjunctiva/metabolism ; Injections, Intraocular ; Cell Proliferation/drug effects ; Neovascularization, Pathologic/drug therapy ; Human Umbilical Vein Endothelial Cells/drug effects ; Retina/metabolism/drug effects ; Drug Delivery Systems/methods ; Mice, Inbred C57BL ; Angiogenesis ; },
abstract = {Neovascularization contributes to various posterior eye segment diseases such as age-related macular degeneration and diabetic retinopathy. RNA nanoparticles were demonstrated previously to enter the corneal and retinal cells after subconjunctival injection for ocular delivery. In the present study, antiangiogenic aptamers (anti-vascular endothelial growth factor (VEGF) and anti-angiopoietin-2 (Ang2) aptamers) were conjugated to RNA nanoparticles. The objectives were to investigate the clearance and distribution of these angiogenesis-inhibiting RNA nanoparticles after subconjunctival injection in vivo and their antiangiogenic effects for inhibiting ocular neovascularization in vitro. The results in the whole-body fluorescence imaging study showed that the clearance of RNA nanoparticles was size-dependent with no significant differences between RNA nanoparticles with and without the aptamers except for pRNA-3WJ. The distribution study of RNA nanoparticles by confocal microscopy of the dissected eye tissues in vivo indicated cell internalization of the larger RNA nanoparticles in the retina and retinal pigment epithelium after subconjunctival injection, and the larger nanoparticles with aptamers showed higher levels of cell internalization than those without. In the cell proliferation assay in vitro, RNA nanoparticles with multiple aptamers had higher antiangiogenic effects. With both longer retention time and high antiangiogenic effect, SQR-VEGF-Ang2 could be a promising RNA nanoparticle for posterior eye delivery.},
}
@article {pmid38656867,
year = {2024},
author = {Emre, T and Chakravarty, A and Rivail, A and Lachinov, D and Leingang, O and Riedl, S and Mai, J and Scholl, HPN and Sivaprasad, S and Rueckert, D and Lotery, A and Schmidt-Erfurth, U and Bogunovic, H},
title = {3DTINC: Time-Equivariant Non-Contrastive Learning for Predicting Disease Progression From Longitudinal OCTs.},
journal = {IEEE transactions on medical imaging},
volume = {43},
number = {9},
pages = {3200-3210},
doi = {10.1109/TMI.2024.3391215},
pmid = {38656867},
issn = {1558-254X},
support = {210572/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Disease Progression ; *Imaging, Three-Dimensional/methods ; Deep Learning ; Algorithms ; Macular Degeneration/diagnostic imaging ; Image Interpretation, Computer-Assisted/methods ; Supervised Machine Learning ; Retina/diagnostic imaging ; },
abstract = {Self-supervised learning (SSL) has emerged as a powerful technique for improving the efficiency and effectiveness of deep learning models. Contrastive methods are a prominent family of SSL that extract similar representations of two augmented views of an image while pushing away others in the representation space as negatives. However, the state-of-the-art contrastive methods require large batch sizes and augmentations designed for natural images that are impractical for 3D medical images. To address these limitations, we propose a new longitudinal SSL method, 3DTINC, based on non-contrastive learning. It is designed to learn perturbation-invariant features for 3D optical coherence tomography (OCT) volumes, using augmentations specifically designed for OCT. We introduce a new non-contrastive similarity loss term that learns temporal information implicitly from intra-patient scans acquired at different times. Our experiments show that this temporal information is crucial for predicting progression of retinal diseases, such as age-related macular degeneration (AMD). After pretraining with 3DTINC, we evaluated the learned representations and the prognostic models on two large-scale longitudinal datasets of retinal OCTs where we predict the conversion to wet-AMD within a six-month interval. Our results demonstrate that each component of our contributions is crucial for learning meaningful representations useful in predicting disease progression from longitudinal volumetric scans.},
}
@article {pmid38654807,
year = {2024},
author = {Parrey, MUR and Abdul-Latif, MM and Alruwaili, SMM and Alshammari, KHS and Alsayer, RIA and Alanazi, NKJ and Abd El Mawgod, MM},
title = {Public Awareness of Common Age-Related Eye Diseases in Northern Saudi Arabia.},
journal = {Cureus},
volume = {16},
number = {3},
pages = {e56841},
pmid = {38654807},
issn = {2168-8184},
abstract = {UNLABELLED: Background: Visual impairment and blindness pose substantial public health challenges in Saudi Arabia, especially among the elderly susceptible to blinding eye diseases. Assessing awareness of age-related eye diseases (AREDs) is vital for addressing vision loss in this demographic. However, there is a lack of research on ARED awareness in Northern Saudi Arabia, underscoring the need for evidence-based data from adult populations to craft effective health promotion strategies.<br><br>METHODS: This population-based descriptive survey was conducted on 411 Saudi adults aged 18-70 residing in Arar City,&#xa0;Saudi Arabia, over six months from September 2023. Random sampling was employed, and awareness levels were assessed using a pre-designed questionnaire. Data analysis was performed using Statistical Product and Service Solutions (SPSS, version 20.0; IBM SPSS Statistics for Windows, Armonk, NY).<br><br>RESULTS: &#xa0;Among the 411 participants, 225 (54.7%) were aged 18-29 years, 312 (76%) were females, and 299 (72.6%) held a bachelor's degree or diploma. Regarding awareness, 71.3% knew about cataracts, but nearly half erroneously believed it could be treated solely medically. For diabetic retinopathy (DR), 366 (89%) recognized lifestyle modifications, and 378 (92%) understood screening as preventive measures. Most participants understood prevention methods for all four diseases, but misconceptions about treatment options were observed. Awareness of glaucoma and age-related macular degeneration (ARMD) was lower. No significant age-related differences were found in awareness, except for cataracts (P = 0.001). Education significantly influenced awareness of cataracts, DR, and glaucoma (P = 0.001, 0.013, and 0.008, respectively), but not ARMD (P = 0.606). The study found that the internet is the primary source of information on AREDs for most participants, except for cataracts, where friends and relatives are prominent.<br><br>CONCLUSION: The study reveals varying awareness levels of AREDs among Saudi adults. Although most participants understood preventive measures, misconceptions about treatment underscore the need for accurate education channels. Healthcare professionals must ensure information reliability to effectively combat misinformation and enhance awareness of AREDs.},
}
@article {pmid38654344,
year = {2024},
author = {Driban, M and Yan, A and Selvam, A and Ong, J and Vupparaboina, KK and Chhablani, J},
title = {Artificial intelligence in chorioretinal pathology through fundoscopy: a comprehensive review.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {36},
pmid = {38654344},
issn = {2056-9920},
abstract = {BACKGROUND: Applications for artificial intelligence (AI) in ophthalmology are continually evolving. Fundoscopy is one of the oldest ocular imaging techniques but remains a mainstay in posterior segment imaging due to its prevalence, ease of use, and ongoing technological advancement. AI has been leveraged for fundoscopy to accomplish core tasks including segmentation, classification, and prediction.<br><br>MAIN BODY: In this article we provide a review of AI in fundoscopy applied to representative chorioretinal pathologies, including diabetic retinopathy and age-related macular degeneration, among others. We conclude with a discussion of future directions and current limitations.<br><br>SHORT CONCLUSION: As AI evolves, it will become increasingly essential for the modern ophthalmologist to understand its applications and limitations to improve patient outcomes and continue to innovate.},
}
@article {pmid38654214,
year = {2024},
author = {Boltz, A and Spöttl, T and Huf, W and Weingessel, B and Vécsei-Marlovits, VP},
title = {Effect of intravitreal injections due to neovascular age-related macular degeneration on retinal nerve fiber layer thickness and minimum rim width: a cross sectional study.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {185},
pmid = {38654214},
issn = {1471-2415},
mesh = {Humans ; *Intravitreal Injections ; Cross-Sectional Studies ; Male ; Female ; Aged ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Nerve Fibers/pathology ; *Retinal Ganglion Cells/pathology ; Aged, 80 and over ; Optic Disk/pathology ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Wet Macular Degeneration/drug therapy/diagnosis ; Visual Acuity ; Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; },
abstract = {PURPOSE: The present study tested the hypothesis that repeated anti-VEGF injections are associated with reduced retinal nerve fiber layer (RNFL) and minimum rim width (MRW) of the optic nerve head.<br><br>PATIENTS AND METHODS: Sixty-six patients with a history of intravitreal injections due to neovascular age-related macular degeneration were included. RNFL and MRW were measured using optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany).<br><br>RESULTS: Mean global RNFL was 90.62&#xa0;&#x3bc;m and both RNFL as well as MRW significantly decreased with advanced age (p&#x2009;=&#x2009;0.005 and p&#x2009;=&#x2009;0.019, respectively). Correlating for the number of injections, no significant impact on RNFL was found globally (p&#x2009;=&#x2009;0.642) or in any of the sectors. In contrast, however, global MRW was significantly reduced with increasing numbers of intravitreal injections (p&#x2009;=&#x2009;0.012). The same holds true when adjusted for the confounding factor age (RNFL p&#x2009;=&#x2009;0.566 and MRW p&#x2009;=&#x2009;0.023).<br><br>CONCLUSION: Our study shows that repeated intravitreal injections due to choroidal neovascularization seem to have a deleterious effect on MRW but not on RNFL. This suggests that MRW is a more sensitive marker than RNFL for evaluating the effect of frequent intravitreal injections on the optic nerve head since it seems to be the first structure affected.},
}
@article {pmid38653842,
year = {2024},
author = {Gueddena, Y and Aboudi, N and Zgolli, H and Mabrouk, S and Sidibe, D and Tabia, H and Khlifa, N},
title = {A new intelligent system based deep learning to detect DME and AMD in OCT images.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {191},
pmid = {38653842},
issn = {1573-2630},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Deep Learning ; *Macular Degeneration/diagnosis ; *Macular Edema/diagnosis/diagnostic imaging/etiology ; Diabetic Retinopathy/diagnosis/diagnostic imaging ; Neural Networks, Computer ; Retina/diagnostic imaging/pathology ; Diagnosis, Computer-Assisted/methods ; Aged ; Female ; Male ; },
abstract = {Optical Coherence Tomography (OCT) is widely recognized as the leading modality for assessing ocular retinal diseases, playing a crucial role in diagnosing retinopathy while maintaining a non-invasive modality. The increasing volume of OCT images underscores the growing importance of automating image analysis. Age-related diabetic Macular Degeneration (AMD) and Diabetic Macular Edema (DME) are the most common cause of visual impairment. Early detection and timely intervention for diabetes-related conditions are essential for preventing optical complications and reducing the risk of blindness. This study introduces a novel Computer-Aided Diagnosis (CAD) system based on a Convolutional Neural Network (CNN) model, aiming to identify and classify OCT retinal images into AMD, DME, and Normal classes. Leveraging CNN efficiency, including feature learning and classification, various CNN, including pre-trained VGG16, VGG19, Inception_V3, a custom from scratch model, BCNN (VGG16) 2 , BCNN (VGG19) 2 , and BCNN (Inception_V3) 2 , are developed for the classification of AMD, DME, and Normal OCT images. The proposed approach has been evaluated on two datasets, including a DUKE public dataset and a Tunisian private dataset. The combination of the Inception_V3 model and the extracted feature from the proposed custom CNN achieved the highest accuracy value of 99.53% in the DUKE dataset. The obtained results on DUKE public and Tunisian datasets demonstrate the proposed approach as a significant tool for efficient and automatic retinal OCT image classification.},
}
@article {pmid38653751,
year = {2024},
author = {Montesel, A and Pakeer Muhammed, R and Chandak, S and Kazantzis, D and Thottarath, S and Chandra, S and Chong, V and Burton, BJL and Menon, G and Pearce, I and McKibbin, M and Kotagiri, A and Talks, J and Grabowska, A and Ghanchi, F and Gale, R and Giani, A and Yamaguchi, TCN and Sivaprasad, S},
title = {Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4.},
journal = {Eye (London, England)},
volume = {38},
number = {13},
pages = {2596-2602},
pmid = {38653751},
issn = {1476-5454},
mesh = {Humans ; *Recombinant Fusion Proteins/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Tomography, Optical Coherence/methods ; Male ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Intravitreal Injections ; Aged ; *Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; *Visual Acuity/physiology ; *Subretinal Fluid ; Retrospective Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retinal Pigment Epithelium/pathology ; Fluorescein Angiography/methods ; Retina/pathology/diagnostic imaging ; },
abstract = {PURPOSE: To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept.<br><br>METHODS: Optical coherence tomography (OCT) scans of treatment-na&#xef;ve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness. Response was defined as absence of IRF and SRF. Factors associated with completely resolved STHR versus persistent STHR post-loading phase were compared.<br><br>RESULTS: 2039 eyes of 1901 patients were analysed. STHR was observed in 79 eyes of 78 patients, with an estimated prevalence of 3.87% (95% CI 3.08-4.81%). STHR were seen in 44 type 1 MNV (56%), 27 with type 2 (34%), and 8 with type 3 (10%). At baseline, a total of 303 STHR were present, ranging between 1-22 per eye. The total number of STHR reduced significantly after the loading phase to 173 (p&#x2009;=&#x2009;0.002). Complete disappearance of STHR was seen in 44 eyes (56%) and persistent STHR in the rest (44%).<br><br>CONCLUSIONS: STHR may represent a marker of low-grade exudation in nAMD eyes with good response to a loading phase of aflibercept. However, its potential role as an independent nAMD activity biomarker is limited as most resolve after the loading phase.},
}
@article {pmid38653276,
year = {2024},
author = {Billia, F and Hatz-Wurziger, K},
title = {Persistent and Poor-Responsive Cystoid Macular Edema after Stereotactic Radiotherapy in Neovascular Age-Related Macular Degeneration: A Case Report of Three Patients.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {241},
number = {4},
pages = {459-462},
pmid = {38653276},
issn = {1439-3999},
mesh = {Humans ; *Macular Edema/etiology/therapy ; *Radiosurgery/adverse effects ; Male ; Female ; Aged ; Treatment Outcome ; Aged, 80 and over ; Radiation Injuries/etiology ; Macular Degeneration ; },
}
@article {pmid38650587,
year = {2024},
author = {Song, S and Li, X and Xue, X and Dong, W and Li, C},
title = {Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.},
journal = {International journal of general medicine},
volume = {17},
number = {},
pages = {1479-1491},
pmid = {38650587},
issn = {1178-7074},
abstract = {High temperature requirement A1 (HTRA1) is a member of the serine protease family, comprising four structural domains: IGFBP domain, Kazal domain, protease domain and PDZ domain. HTRA1 encodes a serine protease, a secreted protein that is widely expressed in the vasculature. HTRA1 regulates a wide range of physiological processes through its proteolytic activity, and is also involved in a variety of vascular abnormalities-related diseases. This article reviews the role of HTRA1 in the development of vascular abnormalities-related hereditary cerebral small vessel disease (CSVD), age-related macular degeneration (AMD), tumors and other diseases. Through relevant research advances to understand the role of HTRA1 in regulating signaling pathways or refolding, translocation, degradation of extracellular matrix (ECM) proteins, thus directly or indirectly regulating angiogenesis, vascular remodeling, and playing an important role in vascular homeostasis, further understanding the mechanism of HTRA1's role in vascular abnormality-related diseases is important for HTRA1 to be used as a therapeutic target in related diseases.},
}
@article {pmid38648437,
year = {2024},
author = {Singh, M and Chaurasiya, SK and Radhika, },
title = {Comment on "Efficacy of low-vision devices in the elderly population with age-related macular degeneration".},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {5},
pages = {753},
pmid = {38648437},
issn = {1998-3689},
mesh = {Humans ; *Macular Degeneration/diagnosis ; *Vision, Low/epidemiology ; Aged ; Visual Acuity/physiology ; },
}
@article {pmid38648289,
year = {2024},
author = {Le, NQ and He, W and MacGregor, S},
title = {Polygenic Risk Scores and Genetically Complex Eye Disease.},
journal = {Annual review of vision science},
volume = {10},
number = {1},
pages = {403-423},
doi = {10.1146/annurev-vision-102122-103958},
pmid = {38648289},
issn = {2374-4650},
mesh = {Humans ; *Multifactorial Inheritance/genetics ; Genome-Wide Association Study ; *Genetic Predisposition to Disease ; *Eye Diseases/genetics ; Risk Assessment ; Risk Factors ; Genetic Risk Score ; },
abstract = {The success of genome-wide association studies (GWASs) in uncovering genetic variants associated with complex eye diseases has paved the way for the development of risk prediction approaches based on disease genetics. Derived from GWAS data, polygenic risk scores (PRSs) have been emerging as a promising indicator of an individual's genetic liability to disease. In this review, we recap the current progress of PRS development and utility across a range of common eye diseases. While illustrating the prediction accuracy of PRSs and their valuable role in risk stratification for certain eye diseases, we also address PRSs' uncertain implementation in clinical settings at this stage, particularly in circumstances where limited treatment options are available. Finally, we discuss obstacles in translating PRSs into practice, including barriers to clinical impact, issues when working with different ancestry groups, and communicating risk scores, as well as projections for future improvements.},
}
@article {pmid38648051,
year = {2024},
author = {Zhang, R and Dong, L and Fu, X and Hua, L and Zhou, W and Li, H and Wu, H and Yu, C and Li, Y and Shi, X and Ou, Y and Zhang, B and Wang, B and Ma, Z and Luo, Y and Yang, M and Chang, X and Wang, Z and Wei, W},
title = {Trends in the Prevalence of Common Retinal and Optic Nerve Diseases in China: An Artificial Intelligence Based National Screening.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {4},
pages = {28},
pmid = {38648051},
issn = {2164-2591},
mesh = {Humans ; China/epidemiology ; Prevalence ; Male ; Female ; Middle Aged ; *Artificial Intelligence ; Adult ; Aged ; *Retinal Diseases/epidemiology/diagnosis ; *Optic Nerve Diseases/epidemiology/diagnosis ; Young Adult ; Adolescent ; Mass Screening/methods ; Aged, 80 and over ; },
abstract = {PURPOSE: Retinal and optic nerve diseases have become the primary cause of irreversible vision loss and blindness. However, there is still a lack of thorough evaluation regarding their prevalence in China.<br><br>METHODS: This artificial intelligence-based national screening study applied a previously developed deep learning algorithm, named the Retinal Artificial Intelligence Diagnosis System (RAIDS). De-identified personal medical records from January 2019 to December 2021 were extracted from 65 examination centers in 19 provinces of China. Crude prevalence and age-sex-adjusted prevalence were calculated by mapping to the standard population in the seventh national census.<br><br>RESULTS: In 2021, adjusted referral possible glaucoma (63.29, 95% confidence interval [CI] = 57.12-68.90 cases per 1000), epiretinal macular membrane (21.84, 95% CI = 15.64-29.22), age-related macular degeneration (13.93, 95% CI = 11.09-17.17), and diabetic retinopathy (11.33, 95% CI = 8.89-13.77) ranked the highest among 10 diseases. Female participants had significantly higher adjusted prevalence of pathologic myopia, yet a lower adjusted prevalence of diabetic retinopathy, referral possible glaucoma, and hypertensive retinopathy than male participants. From 2019 to 2021, the adjusted prevalence of retinal vein occlusion (0.99, 95% CI = 0.73-1.26 to 1.88, 95% CI = 1.42-2.44), macular hole (0.59, 95% CI = 0.41-0.82 to 1.12, 95% CI = 0.76-1.51), and hypertensive retinopathy (0.53, 95% CI = 0.40-0.67 to 0.77, 95% CI = 0.60-0.95) significantly increased. The prevalence of diabetic retinopathy in participants under 50 years old significant increased.<br><br>CONCLUSIONS: Retinal and optic nerve diseases are an important public health concern in China. Further well-conceived epidemiological studies are required to validate the observed increased prevalence of diabetic retinopathy, hypertensive retinopathy, retinal vein occlusion, and macular hole nationwide.<br><br>TRANSLATIONAL RELEVANCE: This artificial intelligence system can be a potential tool to monitor the prevalence of major retinal and optic nerve diseases over a wide geographic area.},
}
@article {pmid38648039,
year = {2024},
author = {Williams, BL and Zouache, MA and Seager, NA and Pappas, CM and Liu, J and Anstadt, RA and Hubbard, WC and Thomas, J and Hageman, JL and Mohler, J and Richards, BT and Hageman, GS},
title = {Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {4},
pages = {34},
pmid = {38648039},
issn = {1552-5783},
support = {R24 EY017404/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Female ; Humans ; Male ; Chromosomes, Human, Pair 10/genetics ; Enzyme-Linked Immunosorbent Assay/methods ; Genetic Predisposition to Disease ; *High-Temperature Requirement A Serine Peptidase 1/blood/genetics/metabolism ; *Macular Degeneration/genetics/metabolism/diagnosis ; Risk Factors ; Sensitivity and Specificity ; *Serine Endopeptidases/genetics/metabolism ; *Vitreous Body/metabolism ; },
abstract = {PURPOSE: The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration (AMD) at the 10q26 locus, age, sex, AMD status, and/or AMD disease severity, and, therefore, to determine the contribution of systemic and ocular HtrA1 to the AMD disease process.<br><br>METHODS: A custom-made sandwich ELISA assay (SCTM ELISA) for detection of the HtrA1 protein was designed and compared with three commercial assays (R&amp;D Systems, MyBiosource 1 and MyBiosource 2) using 65 serum samples. Concentrations of HtrA1 were thereafter determined in serum and vitreous samples collected from 248 individuals and 145 human donor eyes, respectively.<br><br>RESULTS: The SCTM ELISA demonstrated high specificity, good recovery, and parallelism within its linear detection range and performed comparably to the R&amp;D Systems assay. In contrast, we were unable to demonstrate the specificity of the two assays from MyBioSource using either recombinant or native HtrA1. Analyses of concentrations obtained using the validated SCTM assay revealed that genetic risk at the 10q26 locus, age, sex, or AMD status are not significantly associated with altered levels of the HtrA1 protein in serum or in vitreous humor (P > 0.05).<br><br>CONCLUSIONS: HtrA1 levels in serum and vitreous do not reflect the risk for AMD associated with the 10q26 locus or disease status. Localized alteration in HTRA1 expression in the retinal pigment epithelium, rather than systemic changes in HtrA1, is the most likely driver of elevated risk for developing AMD among individuals with risk variants at the 10q26 locus.},
}
@article {pmid38646507,
year = {2024},
author = {Zhang, X and Zhu, Z and Huang, Y and Shang, X and O'Brien, TJ and Kwan, P and Ha, J and Wang, W and Liu, S and Zhang, X and Kiburg, K and Bao, Y and Wang, J and Yu, H and He, M and Zhang, L},
title = {Shared genetic aetiology of Alzheimer's disease and age-related macular degeneration by APOC1 and APOE genes.},
journal = {BMJ neurology open},
volume = {6},
number = {1},
pages = {e000570},
pmid = {38646507},
issn = {2632-6140},
abstract = {BACKGROUND: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share similar pathological features, suggesting common genetic aetiologies between the two. Investigating gene associations between AD and AMD may provide useful insights into the underlying pathogenesis and inform integrated prevention and treatment for both diseases.<br><br>METHODS: A stratified quantile-quantile (QQ) plot was constructed to detect the pleiotropy among AD and AMD based on genome-wide association studies data from 17&#x2009;008 patients with AD and 30&#x2009;178 patients with AMD. A Bayesian conditional false discovery rate-based (cFDR) method was used to identify pleiotropic genes. UK Biobank was used to verify the pleiotropy analysis. Biological network and enrichment analysis were conducted to explain the biological reason for pleiotropy phenomena. A diagnostic test based on gene expression data was used to predict biomarkers for AD and AMD based on pleiotropic genes and their regulators.<br><br>RESULTS: Significant pleiotropy was found between AD and AMD (significant leftward shift on QQ plots). APOC1 and APOE were identified as pleiotropic genes for AD-AMD (cFDR <0.01). Network analysis revealed that APOC1 and APOE occupied borderline positions on the gene co-expression networks. Both APOC1 and APOE genes were enriched on the herpes simplex virus 1 infection pathway. Further, machine learning-based diagnostic tests identified that APOC1, APOE (areas under the curve (AUCs) >0.65) and their upstream regulators, especially ZNF131, ADNP2 and HINFP, could be potential biomarkers for both AD and AMD (AUCs >0.8).<br><br>CONCLUSION: In this study, we confirmed the genetic pleiotropy between AD and AMD and identified APOC1 and APOE as pleiotropic genes. Further, the integration of multiomics data identified ZNF131, ADNP2 and HINFP as novel diagnostic biomarkers for AD and AMD.},
}
@article {pmid38645781,
year = {2024},
author = {Angelia, M and Amelia, YS and Pratama, KG},
title = {Mediterranean diet as a modifiable risk factor for age-related macular degeneration: A systematic review and meta-analysis.},
journal = {Tzu chi medical journal},
volume = {36},
number = {2},
pages = {223-230},
pmid = {38645781},
issn = {2223-8956},
abstract = {OBJECTIVES: Age-related macular degeneration (AMD) is a chronic and degenerative disease of the retina that leads to irreversible blindness. There is no proven effective treatment for early AMD and advanced AMD. Mediterranean diet (MD) has been linked to reducing the risk or delaying the progression of AMD. Therefore, in this study, we aim to investigate the potential of MD as a modifiable risk factor for AMD.<br><br>MATERIALS AND METHODS: A systematic search was performed in three databases: PubMed, EBSCO host, and Proquest. We search for studies that determine the association of MD in AMD. Then, we pooled the data for meta-analysis.<br><br>RESULTS: Eight studies were included in our systematic review. Seven studies were included for meta-analysis. Subjects with medium-high (hazard ratio [HR] 0.82; 95% confidence interval [CI]: 0.75-0.90) adherence to the MD showed a reduced risk of developing AMD. Moreover, medium adherence AMD shows a significant and inverse relationship with the progression to advanced AMD (HR: 0.87; 95% CI: 0.81-0.93). Although it is still inconsistent, the reduction appears stronger for geographic atrophy than for neovascular AMD.<br><br>CONCLUSION: Adhering to the MD, particularly at a medium to high level, appears to confer a protective effect against AMD. The sub-analysis demonstrates even that there is a protective effect associated with moderate adherence against advanced AMD. The presence of considerable heterogeneity within the results warrants cautious interpretation. Further research is needed to enhance our understanding.},
}
@article {pmid38643252,
year = {2024},
author = {Takahashi, H and Inoda, S and Takahashi, H and Takahashi, R and Hashimoto, Y and Yoshida, H and Kawashima, H and Yanagi, Y},
title = {One-year visual and anatomical outcomes of intravitreal faricimab injection for neovascular age-related macular degeneration after prior brolucizumab treatment.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {9087},
pmid = {38643252},
issn = {2045-2322},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Choroid ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors ; *Wet Macular Degeneration ; *Antibodies, Bispecific ; *Antibodies, Monoclonal, Humanized ; },
abstract = {This single-center retrospective cohort study analyzed the 1-year real-world treatment outcomes of 63 consecutive eyes (of 60 patients) with neovascular age-related macular degeneration (nAMD) that were switched from intravitreal brolucizumab (IVBr) to intravitreal faricimab (IVF) and managed on a treat-and-extend regimen with discontinuation criteria. After the switch, patients opted to continue IVF, to switch back to IVBr, or receive photodynamic therapy (PDT). Thirty-eight patients continued IVF, 16 patients were switched back to IVBr, 2 patients received PDT, and 4 patients paused treatment. Best-corrected visual acuity (BCVA), central subfield thickness (CST), subfoveal choroidal thickness (sf-CT), and injection intervals were compared immediately before and 1 year after the initial IVF. Whereas there was no change in BCVA and CST; 0 [- 0.0969 to 0.125, P = 0.58], - 1.5 [- 27.8 to 13.5, P = 0.11] µm, respectively, sf-CT decreased significantly; - 19.5 [- 45.5 to 7.75, P = 0.015] µm. The patients switched back showed no significant change in sf-CT. The injection interval extended significantly in the IVF continuation and the switch-back group (2.0 and 3.0 weeks, respectively; [P = 0.0007 and 0.0078]) in eyes with a pre-switching interval of less than 12 weeks. Faricimab shows promise as a safe and effective alternative to brolucizumab for treating nAMD.},
}
@article {pmid38643063,
year = {2024},
author = {Wu, PC and Chiang, WY and Lo, J and Lee, JJ and Chen, YJ and Kuo, HK and Chiau, JS and Hsu, SH and Chen, YH},
title = {Using a Smartphone-Based Chatbot for Postoperative Care After Intravitreal Injection During the COVID-19 Pandemic: Retrospective Cohort Study.},
journal = {JMIR formative research},
volume = {8},
number = {},
pages = {e43022},
pmid = {38643063},
issn = {2561-326X},
abstract = {BACKGROUND: During the COVID-19 pandemic period, it was difficult to carry out regular and scheduled follow-up of patients in the outpatient department, especially during lockdown periods. However, early detection of initial infection or other serious conditions is vital for patients after ocular surgery, such as intravitreal injection (IVI) for age-related macular degeneration (AMD).<br><br>OBJECTIVE: We evaluated the use of a smartphone-based postoperative care chatbot system (PCCS) with an instant bidirectional feedback system for patients to self-report postoperative symptoms and signs.<br><br>METHODS: During the COVID-19 level 3 epidemic alert in July 2021 in Taiwan, the PCCS alerted the patients to report and grade 6 ocular symptoms and signs associated with ocular inflammation or retinal detachment. Patients used the PCCS for 7 days post surgery to assess their symptoms and signs each day after receiving an alert. Data were automatically collected using a cloud computer system, including symptom grades and messages sent to medical staff for further medical assistance. A user satisfaction questionnaire was administered to the patients on the seventh day post surgery.<br><br>RESULTS: In total, 185 patients participated in this study. There were 26 (3.03%) reports of symptom grade deterioration (including increased blurred vision, eye swelling, nausea, and floaters or flashes) from 12 (6.5%) patients. We found no difference in the gender of patients who received an early medical consultation. One case of endophthalmitis was reported, wherein an improvement was observed after prompt administration of IVI antibiotics twice. Overall, 87% (n=185) of patients were satisfied or very satisfied with communicating their symptoms instantly through the app; they were willing to use it again and believed that it could improve the quality of care. Seven of the 185 (3.8%) patients had an earlier medical consultation and 1 (0.5%) had endophthalmitis.<br><br>CONCLUSIONS: The chatbot system, designed for self-reporting postoperative symptoms and providing instant bidirectional feedback on smartphones, could be beneficial for enhancing the quality of care in early medical consultations without gender differences among patients with AMD receiving IVI, and achieved satisfactory responses from patients.},
}
@article {pmid38641181,
year = {2024},
author = {Salehi, MA and Frounchi, N and Zakavi, SS and Mohammadi, S and Harandi, H and Shojaei, S and Gouravani, M and Fernando Arevalo, J},
title = {Retinal and choroidal changes after anti-VEGF therapy in neovascular-AMD patients: A systematic review and meta-analysis of SD-OCT studies.},
journal = {Survey of ophthalmology},
volume = {69},
number = {4},
pages = {547-557},
doi = {10.1016/j.survophthal.2024.04.001},
pmid = {38641181},
issn = {1879-3304},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/therapeutic use ; *Choroid/pathology/diagnostic imaging ; *Intravitreal Injections ; Ranibizumab/therapeutic use/administration &amp; dosage ; Retina/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; },
abstract = {BACKGROUND: In recent years, the progress made in the field of optical coherence tomography has helped to understand the changes in eye layers in patients with exudative age-related macular degeneration (nAMD). Early diagnosis of nAMD, a leading cause of irreversible vision impairment, is helpful. Therefore, we performed a meta-analysis on OCT measurement alterations before and after anti-VEGF therapy in patients with nAMD and controls.<br><br>METHOD: We systematically searched Scopus, PubMed, Cochrane, and Web of Science to find articles that measured choroidal and retinal layer changes after anti-VEGF therapy in nAMD Patients. We chose either a fixed-effects or random-effects model based on the assessed heterogeneity level to perform a meta-analysis. In addition, we conducted meta-regression, subgroup analyses, publication bias, and quality assessment for included studies.<br><br>RESULTS: Thirteen studies were included in the meta-analysis, with 733 total participants. Foveal thickness and subfoveal choroidal thickness (CT) decreased significantly in the first 3 years after injections, except for subfoveal CT in the third year after injection. It also showed that CT at 1500&#xa0;&#xb5;m temporal and nasal to the fovea did not significantly change.<br><br>CONCLUSION: Our results showed anti-VEGF treatment for nAMD patients was associated with a significant reduction in foveal thickness and subfoveal CT in the first 2 years after treatment. Our analysis did not reveal any correlation between changes in foveal thickness and subfoveal CT with best-corrected visual acuity or other factors.},
}
@article {pmid38641006,
year = {2024},
author = {Rosenfeld, PJ and Shen, M and Trivizki, O and Liu, J and Herrera, G and Hiya, FE and Li, J and Berni, A and Wang, L and El-Mulki, OS and Cheng, Y and Lu, J and Zhang, Q and O'Brien, RC and Gregori, G and Wang, RK},
title = {Rediscovering Age-Related Macular Degeneration with Swept-Source OCT Imaging: The 2022 Charles L. Schepens, MD, Lecture.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {9},
pages = {839-853},
doi = {10.1016/j.oret.2024.04.012},
pmid = {38641006},
issn = {2468-6530},
mesh = {Humans ; *Fluorescein Angiography/methods ; *Fundus Oculi ; Macula Lutea/pathology/diagnostic imaging ; Macular Degeneration/diagnosis ; Ophthalmology ; *Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: Swept-source OCT angiography (SS-OCTA) scans of eyes with age-related macular degeneration (AMD) were used to replace color, autofluorescence, infrared reflectance, and dye-based fundus angiographic imaging for the diagnosis and staging of AMD. Through the use of different algorithms with the SS-OCTA scans, both structural and angiographic information can be viewed and assessed using both cross sectional and en face imaging strategies.<br><br>DESIGN: Presented at the 2022 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on September 30,&#xa0;2022.<br><br>PARTICIPANTS: Patients with AMD.<br><br>METHODS: Review of published literature and ongoing clinical research using SS-OCTA imaging in AMD.<br><br>MAIN OUTCOME MEASURES: Swept-source OCT angiography imaging of AMD at different stages of disease progression.<br><br>RESULTS: Volumetric SS-OCTA dense raster scans were used to diagnose and stage both exudative and nonexudative AMD. In eyes with nonexudative AMD, a single SS-OCTA scan was used to detect and measure structural features in the macula such as the area and volume of both typical soft drusen and calcified drusen, the presence and location of hyperreflective foci, the presence of reticular pseudodrusen, also known as subretinal drusenoid deposits, the thickness of the outer retinal layer, the presence and thickness of basal laminar deposits, the presence and area of persistent choroidal hypertransmission defects, and the presence of treatment-na&#xef;ve nonexudative macular neovascularization. In eyes with exudative AMD, the same SS-OCTA scan pattern was used to detect and measure the presence of macular fluid, the presence and type of macular neovascularization, and the response of exudation to treatment with vascular endothelial growth factor inhibitors. In addition, the same scan pattern was used to quantitate choriocapillaris (CC) perfusion, CC thickness, choroidal thickness, and the vascularity of the choroid.<br><br>CONCLUSIONS: Compared with using several different instruments to perform multimodal imaging, a single SS-OCTA scan provides a convenient, comfortable, and comprehensive approach for obtaining qualitative and quantitative anatomic and angiographic information to monitor the onset, progression, and response to therapies in both nonexudative and exudative AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38640269,
year = {2024},
author = {Feng, C and Chu, W and Lin, P and Xu, H and Chen, X},
title = {Switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration: 1-year outcomes.},
journal = {Medicine},
volume = {103},
number = {16},
pages = {e37839},
pmid = {38640269},
issn = {1536-5964},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Endothelial Growth Factors/therapeutic use ; Intravitreal Injections ; Prospective Studies ; Ranibizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Retina ; Tomography, Optical Coherence ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy ; },
abstract = {This study aimed to elucidate 1-year outcomes following switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration (wAMD). In this prospective, open-label, non-controlled clinical trial, 18 patients with wAMD who had multiple recurrences or persistent exudation despite intravitreal injections of anti-vascular endothelial growth factor agents (except aflibercept) received a 3-mg intravitreal aflibercept injection every 4 weeks. Each patient received 3 to 8 injections. The central retinal thickness and fibrovascular pigment epithelial detachment height decreased significantly at 1 month after initiation of the aflibercept injection, and the values were 146 and 163.2 μm, respectively, at the final visit. The morphological improvement was sustained. The intraretinal and subretinal fluid was completely absorbed at the end of the follow-up. The logMAR vision increased from baseline 0.68 to 0.59 (P < .05). No ocular or systemic adverse events occurred. The intravitreal injection of 3-mg aflibercept seems to be feasible in the treatment of wAMD unresponsive to other anti-vascular endothelial growth factor agents.},
}
@article {pmid38639042,
year = {2024},
author = {Verma, A and Nittala, MG and Corradetti, G and Nassisi, M and Velaga, SB and He, Y and Haines, JL and Pericak-Vance, MA and Stambolian, D and Sadda, SR},
title = {Longitudinal Evaluation of the Distribution of Intraretinal Hyper-Reflective Foci in Eyes with Intermediate Age-Related Macular Degeneration.},
journal = {Current eye research},
volume = {49},
number = {12},
pages = {1278-1284},
doi = {10.1080/02713683.2024.2343334},
pmid = {38639042},
issn = {1460-2202},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Disease Progression ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; Follow-Up Studies ; *Visual Acuity/physiology ; Aged, 80 and over ; Middle Aged ; Fluorescein Angiography/methods ; Retrospective Studies ; Macular Degeneration/diagnosis/metabolism ; },
abstract = {PURPOSE: Intraretinal hyper-reflective foci (IHRF) are optical coherence tomography (OCT) risk factors for progression of age-related macular degeneration (AMD). In this study we assess the change in the number and distribution of IHRF over two years.<br><br>METHODS: The axial distribution of IHRF were quantified in eyes with intermediate AMD (iAMD) at baseline and 24&#x2009;months, using a series of 5 sequential equidistant en face OCT retinal slabs generated between the outer border of the internal limiting membrane (ILM) and the inner border of the retinal pigment epithelium (RPE). Following thresholding and binarization, IHRF were quantified in each retinal slab using ImageJ. The change in IHRF number in each slab between baseline and month 24 was calculated.<br><br>RESULTS: Fifty-two eyes showed evidence of IHRF at baseline, and all continued to show evidence of IHRF at 24&#x2009;months (M24). The total average IHRF count/eye increased significantly from 4.67&#x2009;&#xb1;&#x2009;0.63 at baseline to 11.62&#x2009;&#xb1;&#x2009;13.86 at M24 (p&#x2009;<&#x2009;0.001) with a mean increase of 6.94&#x2009;&#xb1;&#x2009;11.12 (range: - 9 to + 60). Overall, at M24, 76.9% eyes showed an increase in IHRF whereas 15.4% of eyes showed a decrease (3 eyes [5.7%] showed no change). There was a greater number of IHRF and a greater increase in IHRF over M24 in the outer slabs.<br><br>CONCLUSIONS: IHRF are most common in the outer retinal layers and tend to increase in number over time. The impact of the distribution and frequency of these IHRF on the overall progression of AMD requires further study.},
}
@article {pmid38636661,
year = {2024},
author = {Lewandowski, D and Gao, F and Imanishi, S and Tworak, A and Bassetto, M and Dong, Z and Pinto, AFM and Tabaka, M and Kiser, PD and Imanishi, Y and Skowronska-Krawczyk, D and Palczewski, K},
title = {Restoring retinal polyunsaturated fatty acid balance and retina function by targeting ceramide in AdipoR1-deficient mice.},
journal = {The Journal of biological chemistry},
volume = {300},
number = {5},
pages = {107291},
pmid = {38636661},
issn = {1083-351X},
support = {I01 BX004939/BX/BLRD VA/United States ; R01 EY028884/EY/NEI NIH HHS/United States ; R01 EY029680/EY/NEI NIH HHS/United States ; R01 EY034501/EY/NEI NIH HHS/United States ; S10 OD021815/OD/NIH HHS/United States ; R01 EY030873/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Receptors, Adiponectin/metabolism/genetics ; Mice ; *Ceramides/metabolism ; *Retina/metabolism/pathology ; Mice, Knockout ; Fatty Acids, Unsaturated/metabolism ; Retinal Pigment Epithelium/metabolism ; Macular Degeneration/metabolism/pathology/genetics ; },
abstract = {Mutations in the adiponectin receptor 1 gene (AdipoR1) lead to retinitis pigmentosa and are associated with age-related macular degeneration. This study explores the effects of AdipoR1 gene deficiency in mice, revealing a striking decline in ω3 polyunsaturated fatty acids (PUFA), an increase in ω6 fatty acids, and elevated ceramides in the retina. The AdipoR1 deficiency impairs peroxisome proliferator-activated receptor α signaling, which is crucial for FA metabolism, particularly affecting proteins associated with FA transport and oxidation in the retina and retinal pigmented epithelium. Our lipidomic and proteomic analyses indicate changes that could affect membrane composition and viscosity through altered ω3 PUFA transport and synthesis, suggesting a potential influence of AdipoR1 on these properties. Furthermore, we noted a reduction in the Bardet-Biedl syndrome proteins, which are crucial for forming and maintaining photoreceptor outer segments that are PUFA-enriched ciliary structures. Diminution in Bardet-Biedl syndrome-proteins content combined with our electron microscopic observations raises the possibility that AdipoR1 deficiency might impair ciliary function. Treatment with inhibitors of ceramide synthesis led to substantial elevation of ω3 LC-PUFAs, alleviating photoreceptor degeneration and improving retinal function. These results serve as the proof of concept for a ceramide-targeted strategy to treat retinopathies linked to PUFA deficiency, including age-related macular degeneration.},
}
@article {pmid38636554,
year = {2024},
author = {Nanji, K and Fung, M and Qian, J and Khan, M and Barbosa, J and Chaudhary, V},
title = {Comparing an electronic clinical information transfer system to traditional fax referrals for patients with suspected neovascular age-related macular degeneration or diabetic macular edema.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {59},
number = {5},
pages = {e614-e615},
doi = {10.1016/j.jcjo.2024.03.020},
pmid = {38636554},
issn = {1715-3360},
mesh = {Humans ; *Diabetic Retinopathy/diagnosis/therapy ; *Macular Edema/diagnosis ; *Referral and Consultation ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Fluorescein Angiography/methods ; Female ; Male ; Electronic Health Records ; Aged ; Retrospective Studies ; },
}
@article {pmid38636518,
year = {2024},
author = {Terao, R and Lee, TJ and Colasanti, J and Pfeifer, CW and Lin, JB and Santeford, A and Hase, K and Yamaguchi, S and Du, D and Sohn, BS and Sasaki, Y and Yoshida, M and Apte, RS},
title = {LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD[+] depletion.},
journal = {Cell reports},
volume = {43},
number = {5},
pages = {114102},
pmid = {38636518},
issn = {2211-1247},
support = {P30 EY002687/EY/NEI NIH HHS/United States ; T32 EY013360/EY/NEI NIH HHS/United States ; R01 EY019287/EY/NEI NIH HHS/United States ; RF1 AG013730/AG/NIA NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; F30 DK130282/DK/NIDDK NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; },
mesh = {*NAD/metabolism ; Animals ; *Liver X Receptors/metabolism ; *Macrophages/metabolism ; *Cellular Senescence/drug effects ; *Cholesterol/metabolism ; *ADP-ribosyl Cyclase 1/metabolism/genetics ; Mice ; *Mice, Inbred C57BL ; Humans ; Macular Degeneration/metabolism/pathology ; Lysosomes/metabolism ; Membrane Glycoproteins/metabolism/genetics ; Male ; },
abstract = {Although dysregulated cholesterol metabolism predisposes aging tissues to inflammation and a plethora of diseases, the underlying molecular mechanism remains poorly defined. Here, we show that metabolic and genotoxic stresses, convergently acting through liver X nuclear receptor, upregulate CD38 to promote lysosomal cholesterol efflux, leading to nicotinamide adenine dinucleotide (NAD[+]) depletion in macrophages. Cholesterol-mediated NAD[+] depletion induces macrophage senescence, promoting key features of age-related macular degeneration (AMD), including subretinal lipid deposition and neurodegeneration. NAD[+] augmentation reverses cellular senescence and macrophage dysfunction, preventing the development of AMD phenotype. Genetic and pharmacological senolysis protect against the development of AMD and neurodegeneration. Subretinal administration of healthy macrophages promotes the clearance of senescent macrophages, reversing the AMD disease burden. Thus, NAD[+] deficit induced by excess intracellular cholesterol is the converging mechanism of macrophage senescence and a causal process underlying age-related neurodegeneration.},
}
@article {pmid38635732,
year = {2024},
author = {Hirono, K and Maruyama-Inoue, M and Yanagi, Y and Kadonosono, K},
title = {Visual outcomes of intraocular inflammation after brolucizumab injection in Japanese patients with neovascular age-related macular degeneration.},
journal = {PloS one},
volume = {19},
number = {4},
pages = {e0302295},
pmid = {38635732},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; Angiogenesis Inhibitors/adverse effects ; Japan ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; *Uveitis ; Inflammation/drug therapy ; Intravitreal Injections ; Steroids ; Receptors, Vascular Endothelial Growth Factor ; *Antibodies, Monoclonal, Humanized ; },
abstract = {PURPOSE: This study investigates the visual outcomes of neovascular age-related macular degeneration (nAMD) patients who developed intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr).<br><br>METHODS: We studied 285 eyes of 279 cases diagnosed with nAMD and focused on 18 eyes (6.3%) of 17 cases which developed IOI after IVBr. IVBr was performed either on the initial treatment or for switching of other anti-vascular endothelial growth factor agents during January 2020 to December 2021. We evaluated clinical features and the course of treatment of a 6-month follow-up after IOI occurred.<br><br>RESULTS: Of 17 cases, 9 cases were male, 8 cases were female. Baseline logarithm of the minimum angle of resolution(logMAR) best-corrected visual acuity (BCVA) was 0.36, BCVA before IOI occurred was 0.30, and BCVA when IOI occurred was 0.43. 16 eyes (88.9%) had symptoms such as visual loss or floaters when IOI occurred. On the other hand, the remaining 2 eyes (11.1%) had no symptoms. 11 eyes (61.1%) had only IOI, while the remaining 7 eyes (38.9%) had IOI and perivascular sheathing. Steroid sub-tenon injection was performed on 1 eye (5.6%), steroid eye drops were used in 11 eyes (61.1%), and 6 eyes (33.3%) were followed-up without treatment. Neovascular AMD recurred in 16 eyes (88.9%) after IOI occurred and were treated with aflibercept. VA at 3 and 6 months after IOI occurred were significantly improved to 0.34 and 0.30, respectively (P = 0.09 at 3 months and P = 0.02 at 6 months). The symptoms of patients were improved in all cases. We were able to stop steroid treatment in all cases.<br><br>CONCLUSIONS: IOI occurred in 6.3% of nAMD patients after IVBr treatment. All of which showed significant improvement from logMAR of 0.43 to 0.30 with steroid treatment or without any treatment. We should consider the possibility of IOI after IVBr as a complication, however, they have a relatively good prognosis if treated at an early stage.},
}
@article {pmid38635505,
year = {2024},
author = {Schustak, J and Han, H and Bond, K and Huang, Q and Saint-Geniez, M and Bao, Y},
title = {Phenotypic high-throughput screening identifies aryl hydrocarbon receptor agonism as common inhibitor of toxin-induced retinal pigment epithelium cell death.},
journal = {PloS one},
volume = {19},
number = {4},
pages = {e0301239},
pmid = {38635505},
issn = {1932-6203},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; *High-Throughput Screening Assays ; Receptors, Aryl Hydrocarbon/metabolism ; Apoptosis ; Cell Death ; Oxidative Stress ; },
abstract = {The retinal pigment epithelium (RPE) is essential to maintain retinal function, and RPE cell death represents a key pathogenic stage in the progression of several blinding ocular diseases, including age-related macular degeneration (AMD). To identify pathways and compounds able to prevent RPE cell death, we developed a phenotypic screening pipeline utilizing a compound library and high-throughput screening compatible assays on the human RPE cell line, ARPE-19, in response to different disease relevant cytotoxic stimuli. We show that the metabolic by-product of the visual cycle all-trans-retinal (atRAL) induces RPE apoptosis, while the lipid peroxidation by-product 4-hydroxynonenal (4-HNE) promotes necrotic cell death. Using these distinct stimuli for screening, we identified agonists of the aryl hydrocarbon receptor (AhR) as a consensus target able to prevent both atRAL mediated apoptosis and 4-HNE-induced necrotic cell death. This works serves as a framework for future studies dedicated to screening for inhibitors of cell death, as well as support for the discussion of AhR agonism in RPE pathology.},
}
@article {pmid38635383,
year = {2024},
author = {Chakravarty, A and Emre, T and Leingang, O and Riedl, S and Mai, J and Scholl, HPN and Sivaprasad, S and Rueckert, D and Lotery, A and Schmidt-Erfurth, U and Bogunovic, H},
title = {Morph-SSL: Self-Supervision With Longitudinal Morphing for Forecasting AMD Progression From OCT Volumes.},
journal = {IEEE transactions on medical imaging},
volume = {43},
number = {9},
pages = {3224-3239},
pmid = {38635383},
issn = {1558-254X},
support = {/WT_/Wellcome Trust/United Kingdom ; FG 903/FWF_/Austrian Science Fund FWF/Austria ; 210572/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Macular Degeneration/diagnostic imaging ; *Disease Progression ; *Tomography, Optical Coherence/methods ; Image Interpretation, Computer-Assisted/methods ; Deep Learning ; Aged ; Algorithms ; Supervised Machine Learning ; },
abstract = {The lack of reliable biomarkers makes predicting the conversion from intermediate to neovascular age-related macular degeneration (iAMD, nAMD) a challenging task. We develop a Deep Learning (DL) model to predict the future risk of conversion of an eye from iAMD to nAMD from its current OCT scan. Although eye clinics generate vast amounts of longitudinal OCT scans to monitor AMD progression, only a small subset can be manually labeled for supervised DL. To address this issue, we propose Morph-SSL, a novel Self-supervised Learning (SSL) method for longitudinal data. It uses pairs of unlabelled OCT scans from different visits and involves morphing the scan from the previous visit to the next. The Decoder predicts the transformation for morphing and ensures a smooth feature manifold that can generate intermediate scans between visits through linear interpolation. Next, the Morph-SSL trained features are input to a Classifier which is trained in a supervised manner to model the cumulative probability distribution of the time to conversion with a sigmoidal function. Morph-SSL was trained on unlabelled scans of 399 eyes (3570 visits). The Classifier was evaluated with a five-fold cross-validation on 2418 scans from 343 eyes with clinical labels of the conversion date. The Morph-SSL features achieved an AUC of 0.779 in predicting the conversion to nAMD within the next 6 months, outperforming the same network when trained end-to-end from scratch or pre-trained with popular SSL methods. Automated prediction of the future risk of nAMD onset can enable timely treatment and individualized AMD management.},
}
@article {pmid38634408,
year = {2024},
author = {Akkewar, AS and Mishra, KA and Kamble, MG and Kumar, S and Dey, J and Sethi, KK},
title = {A mechanistic review on growing multiple therapeutic applications of lutein and its global market research.},
journal = {Phytotherapy research : PTR},
volume = {38},
number = {6},
pages = {3190-3217},
doi = {10.1002/ptr.8197},
pmid = {38634408},
issn = {1099-1573},
mesh = {Humans ; *Lutein/therapeutic use/pharmacology ; Macular Degeneration/drug therapy ; Antioxidants/pharmacology/therapeutic use ; Diabetic Retinopathy/drug therapy ; Animals ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; },
abstract = {Lutein is a naturally occurring carotenoid synthesized by plants and algae that has a beneficial effect on several biological processes and associated ailments. Its immediate application is in ophthalmology, where it significantly lowers the incidences of age-related macular degeneration (AMD). It also has anti-inflammatory action, treatment of diabetic retinopathy, and cataracts, and enhancement of visual contrast. To critically assess lutein biosynthesis, therapeutic applicability, and market research literature. We have discussed its theoretical frameworks, experimental evidence, limitations, as well as clinical trial results, and future research prospects. The literature for this review article was mined and compiled by collecting and analyzing articles from several databases, including ScienceDirect, Google Scholar, PubMed, Wiley Online Library, Patentscope, and ClinicalTrials.gov published until March 30, 2022. Patent publications were identified using the search terms like IC:(C07C67/56) AND EN_AB:(lutein) OR EN_TI:(lutein) OR EN_AB:(extraction) OR EN_TI:(process). According to the literature, lutein is an essential nutrient given that it cannot be synthesized in the human body and acts as an antioxidant, affecting AMD, diabetic retinopathy, Rheumatic diseases, inflammation, and cancer. Due to inadequate production and laborious extraction, lutein is expensive despite its high demand and applicability. Market research predicts a 6.3% compound annual growth rate for lutein by 2032. Optimizing lutein extraction for high yield and purity is necessary. Lutein has proven applicability in various ailments as well as cosmetics that can be developed as a candidate drug for various diseases discussed in the review.},
}
@article {pmid38633983,
year = {2024},
author = {Rinaldi, M and Pezone, A and Quadrini, GI and Abbadessa, G and Laezza, MP and Passaro, ML and Porcellini, A and Costagliola, C},
title = {Targeting shared pathways in tauopathies and age-related macular degeneration: implications for novel therapies.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1371745},
pmid = {38633983},
issn = {1663-4365},
abstract = {The intricate parallels in structure and function between the human retina and the central nervous system designate the retina as a prospective avenue for understanding brain-related processes. This review extensively explores the shared physiopathological mechanisms connecting age-related macular degeneration (AMD) and proteinopathies, with a specific focus on tauopathies. The pivotal involvement of oxidative stress and cellular senescence emerges as key drivers of pathogenesis in both conditions. Uncovering these shared elements not only has the potential to enhance our understanding of intricate neurodegenerative diseases but also sets the stage for pioneering therapeutic approaches in AMD.},
}
@article {pmid38633250,
year = {2024},
author = {Giralt, L and Figueras-Roca, M and Eguileor, BL and Romero, B and Zarranz-Ventura, J and Alforja, S and Santiago, F and Bolaños, J and Lozano, F and Dotti-Boada, M and Sala-Puigdollers, A and Dura, P and Izquierdo-Serra, J and Valero, O and Adan, A and Fonollosa, A and Molins, B},
title = {C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1330913},
pmid = {38633250},
issn = {1664-3224},
mesh = {Female ; Humans ; Male ; Biomarkers ; *C-Reactive Protein/analysis/metabolism ; *Complement Factor H/analysis/metabolism ; Cross-Sectional Studies ; *Macular Degeneration/diagnosis/metabolism ; },
abstract = {PURPOSE: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters.<br><br>METHODS: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters.<br><br>RESULTS: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) &#xb5;g/mL vs 415.2 (106.1-1962.2) &#xb5;g/mL; p=0.039] and FH levels <200 &#xb5;g/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023).<br><br>CONCLUSION: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.},
}
@article {pmid38633073,
year = {2024},
author = {Arias, A and Montagud-Martinez, D and Artal, P},
title = {Effects of intraocular scatter on near peripheral vision.},
journal = {Biomedical optics express},
volume = {15},
number = {4},
pages = {2517-2523},
pmid = {38633073},
issn = {2156-7085},
abstract = {Both cataracts and age-related macular degeneration (AMD) may occur with aging and are often developed simultaneously. We performed a study to better characterize the impact of induced scatter on the quality of vision in the near periphery, a region where individuals with AMD typically maintain their functional vision. We used an optical instrument as a cataract simulator based on projecting at the eye's pupil plane phase masks with controlled spatial properties generated with a spatial light modulator. The phase wavefronts were designed to accurately replicate the angular distribution of light intensity in the retina found in cataractous eyes with different severities. The induced amount of scatter ranged from values of straylight (S) from 10 to 85 degree[2]/sr, which corresponds from normal aging eye to advanced cataract stages. Mesopic visual acuity (VA) and contrast sensitivity (CS) at 3 cycles per degree were measured at the fovea and two retinal eccentricities (5 and 10 degrees in nasal visual field). We observed a consistent linear decline in VA (expressed in LogMAR) as the amount of induced scatter (quantified by the straylight parameter S) increased, both at the fovea and in the periphery. The effect of induced scattering on mesopic VA and CS at the fovea and the near periphery was evaluated. We found a relatively lower impact of scatter in the near periphery. This may explain the modest improvement in vision often found after cataract surgery in patients with AMD.},
}
@article {pmid38632537,
year = {2024},
author = {Dou, R and Chu, Y and Han, Q and Zhang, W and Bi, X},
title = {Giant retinal pigment epithelium tears with membranous nephropathy: a case report and literature review.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {177},
pmid = {38632537},
issn = {1471-2415},
support = {ZC20166//Tianjin Health Research Project/ ; TJWJ2022MS040//Tianjin Health Research Project/ ; NKYKK202206//Nankai University Eye Institute/ ; NKYKK202203//Nankai University Eye Institute/ ; YKYB1902//Tianjin Eye Hospital Research Project/ ; TJYXZDXK-016A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; 82360208//National Natural Science Foundation of China/ ; },
mesh = {Male ; Humans ; Aged ; Retinal Pigment Epithelium/pathology ; *Glomerulonephritis, Membranous/complications/pathology ; *Macular Degeneration/pathology ; Fluorescein Angiography/methods ; *Retinal Perforations/etiology ; *Retinal Detachment/etiology ; Tomography, Optical Coherence/methods ; Epithelium ; Immunoglobulin G ; },
abstract = {BACKGROUND: Kidney and eye diseases may be closely linked. Tears of the retinal pigment epithelium (RPE) have been reported to be related to kidney diseases, such as IgA nephropathy and light-chain deposition disease. However, pigment epithelium tears associated with membranous nephropathy have not been reported or systematically analysed.<br><br>CASE PRESENTATION: A 68-year-old man presented with decreased right eye visual acuity. Optical coherence tomography (OCT) revealed cystic macular edema, localized serous detachment of the retina and loss of the outer retinal structure in the right eye and retinal pigment epithelium detachment (PED) combined with serous detachment of the retina in the left eye. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) revealed giant RPE tears in the right eye and exudative age-related macular degeneration in the left eye. The patient also suffered from severe membranous nephropathy-autoimmune glomerulonephritis. Renal biopsy immunofluorescence revealed a roughly granular pattern, with immunoglobulin G (IgA), immunoglobulin G (IgG), IgM, complement C3(Components 3), &#x3bb; light chain and &#x3ba; light chain subepithelial staining.<br><br>CONCLUSIONS: It is hypothesized that severe membranous nephropathy caused immune complex deposition on the surface of Bruch membrane, resulting in weakened adhesion between the RPE and Bruch membrane and impaired RPE pump function, combined with age-related macular degeneration, leading to giant RPE tears in the right eye. Close attention should be given to the ocular condition of patients with membranous nephropathy to facilitate timely treatment and avoid serious consequences.},
}
@article {pmid38631656,
year = {2024},
author = {Lindenberg, S and Mahmoudi, A and Oncel, D and Corradetti, G and Oncel, D and Emamverdi, M and Almidani, L and Farahani, A and Wakatsuki, Y and He, Y and Saju M, S and Lee, WK and Wykoff, CC and Sarraf, D and Freund, KB and Sadda, SR},
title = {Acquired Vitelliform Lesions in Intermediate Age-Related Macular Degeneration: A Cross Sectional Study.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {9},
pages = {854-862},
doi = {10.1016/j.oret.2024.04.009},
pmid = {38631656},
issn = {2468-6530},
mesh = {Humans ; Cross-Sectional Studies ; Retrospective Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; Aged ; *Fluorescein Angiography/methods ; *Visual Acuity ; *Fundus Oculi ; *Vitelliform Macular Dystrophy/diagnosis ; Choroid/pathology/diagnostic imaging ; Retinal Drusen/diagnosis ; Aged, 80 and over ; Middle Aged ; Follow-Up Studies ; Macular Degeneration/diagnosis ; },
abstract = {PURPOSE: This study aims to define the characteristics of acquired vitelliform lesions (AVLs) in patients with intermediate age-related macular degeneration (iAMD).<br><br>DESIGN: Retrospective, observational, cross sectional study.<br><br>SUBJECTS: This study included 217 eyes with AVLs associated with iAMD, and an equivalent number of control patients.<br><br>METHODS: OCT scans were evaluated for qualitative and quantitative parameters at both the eye and lesion level. Eye-level parameters included the presence of: hyporeflective core drusen, intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits, macular pachyvessels, central retinal thickness, and central choroidal thickness. Lesion-level qualitative parameters included the presence of ellipsoid zone (EZ) and external limiting membrane disruption overlying the AVL, IHRF overlying the AVL, AVL overlying drusen, pachyvessels under the AVL, a solid core within AVL, and AVL location. Lesion-level quantitative characteristics included AVL height and width, AVL distance from the fovea, and sub-AVL choroidal thickness.<br><br>MAIN OUTCOME MEASURES: The primary outcomes assessed included the frequency of IHRF, the presence of macular pachyvessels, central choroidal thickness, and the dimensions (both height and width) of AVLs.<br><br>RESULTS: Comparing the AVL and control groups, the frequency of IHRF (AVL: 49.3% vs. control: 26.3%) and macular pachyvessels (37.3% vs. 6.9%) was significantly higher in the AVL case group, and the central choroidal thickness (256.8 &#xb1; 88 &#x3bc;m vs. 207.1&#xb1; 45 &#x3bc;m) was thicker in the AVL group. Acquired vitelliform lesions located over drusen, with overlying IHRF, or situated subfoveally, and AVL lesions with EZ disruption were found to have a greater lesion height and width compared with AVL lesions lacking these characteristics (P value < 0.001 for all). Additionally, a significant negative correlation was observed between the distance from the fovea and AVL height (Spearman rho:&#xa0;-0.19, P&#xa0;= 0.002) and width (Spearman rho:&#xa0;-0.30, P&#xa0;= 0.001).<br><br>CONCLUSIONS: This study represents the largest reported cohort of AVL lesions associated with iAMD. Novel findings include the higher frequency of pachyvessels in addition to the presence of a thicker choroid in these eyes, as well as the greater height and width of AVL closer to the foveal center. These findings may offer insights into pathophysiologic mechanisms underlying the development of AVL.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38630675,
year = {2024},
author = {Bowles Johnson, KE and Tang, JAH and Kunala, K and Huynh, KT and Parkins, K and Yang, Q and Hunter, JJ},
title = {Fluorescence Lifetime Imaging of Human Retinal Pigment Epithelium in Pentosan Polysulfate Toxicity Using Adaptive Optics Scanning Light Ophthalmoscopy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {4},
pages = {27},
pmid = {38630675},
issn = {1552-5783},
support = {P30 EY001319/EY/NEI NIH HHS/United States ; R01 EY012951/EY/NEI NIH HHS/United States ; R01 EY032116/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Middle Aged ; Aged ; *Retinal Pigment Epithelium ; Pentosan Sulfuric Polyester ; Retina ; Ophthalmoscopy/methods ; *Retinal Degeneration ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive optics (AO) ophthalmoscopy provides the confocality to measure fluorescence lifetime (FL) primarily from the retinal pigment epithelium (RPE) whereas clinical FLIO has greater influence from fluorophores in the inner retina and lens. Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) measures of FL in vivo could provide insight into RPE health at different stages of disease. In this study, we assess changes in pentosan polysulfate sodium (PPS) toxicity, a recently described toxicity that has clinical findings similar to advanced age-related macular degeneration.<br><br>METHODS: AOFLIO was performed on three subjects with PPS toxicity (57-67&#xa0;years old) and six age-matched controls (50-64&#xa0;years old). FL was analyzed with a double exponential decay curve fit and with phasor analysis. Regions of interest (ROIs) were subcategorized based on retinal features on optical coherence tomography (OCT) and compared to age-matched controls.<br><br>RESULTS: Twelve ROIs from PPS toxicity subjects met the threshold for analysis by curve fitting and 15 ROIs met the threshold for phasor analysis. Subjects with PPS toxicity had prolonged FL compared to age-matched controls. ROIs of RPE degeneration had the longest FLs, with individual pixels extending longer than 900 ps.<br><br>CONCLUSIONS: Our study shows evidence that AOFLIO can provide meaningful information in outer retinal disease beyond what is obtainable from fluorescence intensity alone. More studies are needed to determine the prognostic value of AOFLIO.},
}
@article {pmid38630375,
year = {2024},
author = {Sato, T and Kuniyoshi, K and Hayashi, T and Nishiwaki, H and Mizobuchi, K and Kusaka, S},
title = {Clinical course of two siblings with potassium voltage-gated channel modifier subfamily V member 2 (KCNV2)-associated retinopathy.},
journal = {Documenta ophthalmologica. Advances in ophthalmology},
volume = {148},
number = {3},
pages = {173-182},
pmid = {38630375},
issn = {1573-2622},
support = {22K09825//Japan Society for the Promotion of Science/ ; 21K09756//Japan Society for the Promotion of Science/ ; },
mesh = {Child, Preschool ; Female ; Humans ; Male ; *Cone Dystrophy/genetics ; DNA/genetics ; DNA Mutational Analysis ; Electroretinography ; Mutation, Missense ; Pedigree ; Phenotype ; *Potassium Channels, Voltage-Gated/genetics ; Retina/physiopathology ; Siblings ; Tomography, Optical Coherence ; *Visual Acuity/physiology ; *Eye Diseases, Hereditary/genetics ; },
abstract = {BACKGROUND: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR.<br><br>CASE REPORTS: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27&#xa0;years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T&#x2009;>&#x2009;C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3&#xa0;years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24&#xa0;years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene.<br><br>CONCLUSIONS: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR.},
}
@article {pmid38627341,
year = {2024},
author = {Herardot, E and Liboz, M and Lamour, G and Malo, M and Plancheron, A and Habeler, W and Geiger, C and Frank, E and Campillo, C and Monville, C and Ben M'Barek, K},
title = {Biomechanical Characterization of Retinal Pigment Epitheliums Derived from hPSCs Using Atomic Force Microscopy.},
journal = {Stem cell reviews and reports},
volume = {20},
number = {5},
pages = {1340-1352},
pmid = {38627341},
issn = {2629-3277},
support = {ANR-19-CE18-0004//Agence Nationale de la Recherche/ ; PME201906008797//FRM/ ; },
mesh = {*Microscopy, Atomic Force ; *Retinal Pigment Epithelium/metabolism/ultrastructure/cytology ; Humans ; Pluripotent Stem Cells/cytology/metabolism ; Cell Differentiation ; Biomechanical Phenomena ; Cell Line ; },
abstract = {The retinal pigment epithelium (RPE), a multifunctional cell monolayer located at the back of the eye, plays a crucial role in the survival and homeostasis of photoreceptors. Dysfunction or death of RPE cells leads to retinal degeneration and subsequent vision loss, such as in Age-related macular degeneration and some forms of Retinitis Pigmentosa. Therefore, regenerative medicine that aims to replace RPE cells by new cells obtained from the differentiation of human pluripotent stem cells, is the focus of intensive research. However, despite their critical interest in therapy, there is a lack of biomechanical RPE surface description. Such biomechanical properties are tightly related to their functions. Herein, we used atomic force microscopy (AFM) to analyze both the structural and mechanical properties of RPEs obtained from four cell lines and at different stages of epithelial formation. To characterize epitheliums, we used apical markers in immunofluorescence and showed the increase of transepithelial resistance, as well as the ability to secrete cytokines with an apico-basal polarity. Then, we used AFM to scan the apical surface of living or fixed RPE cells. We show that RPE monolayers underwent softening of apical cell center as well as stiffening of cell borders over epithelial formation. We also observed apical protrusions that depend on actin network, suggesting the formation of microvilli at the surface of RPE epitheliums. These RPE cell characteristics are essential for their functions into the retina and AFM studies may improve the characterization of the RPE epithelium suitable for cell therapy.},
}
@article {pmid38625618,
year = {2024},
author = {Takizawa, H and Yasuda, M and Hoshi, K and Okabe, T and Kunikata, H and Nakazawa, T},
title = {Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {181},
pmid = {38625618},
issn = {1573-2630},
mesh = {Humans ; Female ; Male ; Middle Aged ; Aged ; Aged, 80 and over ; Ranibizumab ; *Biosimilar Pharmaceuticals ; Intravitreal Injections ; Longitudinal Studies ; Retrospective Studies ; *Optic Disk ; *Macular Degeneration/diagnosis/drug therapy ; *Antibodies, Monoclonal, Humanized ; },
abstract = {PURPOSE: To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr).<br><br>METHODS: This retrospective longitudinal study included 43 eyes of 43 patients (74.5&#x2009;&#xb1;&#x2009;9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures.<br><br>RESULTS: In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p&#x2009;<&#x2009;0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p&#x2009;=&#x2009;0.56, p&#x2009;=&#x2009;1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p&#x2009;=&#x2009;0.04; Ch: p&#x2009;=&#x2009;0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.},
}
@article {pmid38625500,
year = {2024},
author = {Roubelat, FP and Barioulet, L and Varenne, F and Escudier, C and Meyer, P and Gomane, C and Butterworth, J and Pagot-Mathis, V and Fournié, P and Gualino, V and Soler, V},
title = {The Reinforced Treat-and-Extend Protocol for Exudative Age-Related Macular Degeneration: Retrospective Assessment of 24-Month Real-World Outcomes in France.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {6},
pages = {1647-1667},
pmid = {38625500},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies).<br><br>METHODS: This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24&#xa0;months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups).<br><br>RESULTS: Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2&#x2009;&#xb1;&#x2009;7.8&#xa0;years). After 24&#xa0;months, mean BCVA significantly improved (65.22&#x2009;&#xb1;&#x2009;14 vs. 71.96&#x2009;&#xb1;&#x2009;13 Early Treatment Diabetic Retinopathy Study letters; p&#x2009;<&#x2009;0.001) and CRT significantly decreased (388.6&#x2009;&#xb1;&#x2009;104 vs. 278.8&#x2009;&#xb1;&#x2009;51&#xa0;&#x3bc;M; p&#x2009;<&#x2009;0.001) with 21% of eyes showing signs of exudation. Over the 24&#xa0;months, a mean total of 14.9&#x2009;&#xb1;&#x2009;4.0 injections and 8.6&#x2009;&#xb1;&#x2009;1.4 consultations were performed. Mean 24-month injection interval was 7.9&#x2009;&#xb1;&#x2009;2.3&#xa0;weeks. Initial and 24-month ophthalmic outcomes for eyes in the strict (47%) versus modified (53%) groups were not significantly different, but mean time interval to first recurrence of disease activity was significantly shorter for the modified group (7.3&#x2009;&#xb1;&#x2009;2.4 vs. 9.9&#x2009;&#xb1;&#x2009;2.5&#xa0;weeks; p&#x2009;<&#x2009;0.001). Patients in the strict RTE group received significantly less injections (13.9&#x2009;&#xb1;&#x2009;3.6 vs. 16.5&#x2009;&#xb1;&#x2009;3.9; p&#x2009;=&#x2009;0.006) and mean 24-month injection interval was significantly longer (9.5&#x2009;&#xb1;&#x2009;2.7 vs. 6.5&#x2009;&#xb1;&#x2009;2.1&#xa0;weeks; p&#x2009;<&#x2009;0.001). Consultation number was similar (8.5&#x2009;&#xb1;&#x2009;1.9 vs. 8.8&#x2009;&#xb1;&#x2009;1.6; p&#x2009;=&#x2009;0.93). Treatment with aflibercept versus ranibizumab did not influence ophthalmic or management outcomes.<br><br>CONCLUSIONS: The RTE protocol, even when modified, reduced consultations but improved ophthalmic outcomes. The RTE protocol could reduce hospital visits and overall burden while also encouraging better patient compliance. Video Abstract available for this article.<br><br>VIDEO ABSTRACT: Vincent Soler and Fran&#xe7;ois-Philippe Roubelat summarize the Reinforced Treat-and-Extend Protocol and main results (MP4 225022 KB).},
}
@article {pmid38625447,
year = {2024},
author = {Hosokawa, MM and Ouchi, C and Shiode, Y and Kimura, S and Matoba, R and Morita, T and Morizane, Y},
title = {Influence of submacular hemorrhage at baseline on the long-term outcomes of aflibercept treatment for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {10},
pages = {3099-3107},
pmid = {38625447},
issn = {1435-702X},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage ; Retrospective Studies ; Male ; Female ; *Intravitreal Injections ; *Visual Acuity ; Aged ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Follow-Up Studies ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Polyps/diagnosis/drug therapy/physiopathology ; *Fundus Oculi ; Treatment Outcome ; Time Factors ; Retinal Hemorrhage/diagnosis/etiology/physiopathology/drug therapy ; Choroid/blood supply ; Choroidal Neovascularization/drug therapy/diagnosis/physiopathology/etiology ; Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Macula Lutea/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Middle Aged ; Polypoidal Choroidal Vasculopathy ; },
abstract = {PURPOSE: To investigate the influence of submacular hemorrhage (SMH) at baseline on long-term visual outcomes of patients with typical age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept (IVA).<br><br>METHODS: In this retrospective study, eyes of treatment-na&#xef;ve patients with tAMD and PCV who initiated IVA under a treat-and-extend regimen and were followed up for&#x2009;&#x2265;&#x2009;5&#xa0;years were classified into the tAMD-SMH (&#x2009;+), tAMD-SMH (-), PCV-SMH (&#x2009;+), and PCV-SMH (-) groups based on the presence of SMH at baseline. Best-corrected visual acuity (BCVA) changes and macular fibrosis and atrophy incidences were assessed.<br><br>RESULTS: This study included 127 eyes (127 patients), including 51 with tAMD and 76 with PCV; 18 eyes had SMH at baseline. In the tAMD-SMH (&#x2009;+) group (n&#x2009;=&#x2009;6), the mean logMAR BCVA significantly deteriorated&#xa0;from 0.59&#x2009;&#xb1;&#x2009;0.45 at baseline to 0.88&#x2009;&#xb1;&#x2009;0.47 at the final visit (P&#x2009;=&#x2009;0.024). No significant BCVA changes were observed in the tAMD-SMH (-) (n&#x2009;=&#x2009;45), PCV-SMH (&#x2009;+) (n&#x2009;=&#x2009;12), or PCV-SMH (-) (n&#x2009;=&#x2009;64) groups (all P&#x2009;>&#x2009;0.05). The tAMD-SMH (&#x2009;+) group showed a significantly higher incidence of macular fibrosis at the final visit than did the tAMD-SMH (-) group (P&#x2009;=&#x2009;0.042). There was no influence of baseline SMH on the macular fibrosis incidence in eyes with PCV and the macular atrophy incidence in eyes with tAMD and PCV.<br><br>CONCLUSION: The presence of SMH at baseline resulted in poorer long-term visual acuity in eyes with tAMD, even with aflibercept treatment. However, no such influence was observed in eyes with PCV.},
}
@article {pmid38622330,
year = {2024},
author = {Sepah, YJ and Do, DV and Mesquida, M and Day, BM and Blotner, S and Afridi, R and Halim, MS and Hong, K and Wakshull, E and Fauser, S and Stoilov, I and Dong Nguyen, Q and , and , },
title = {Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy.},
journal = {Eye (London, England)},
volume = {38},
number = {9},
pages = {1755-1761},
pmid = {38622330},
issn = {1476-5454},
support = {NA//Genentech (Genentech, Inc.)/ ; },
mesh = {Humans ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Interleukin-6/metabolism ; *Visual Acuity/physiology ; *Aqueous Humor/metabolism ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Male ; Female ; *Intravitreal Injections ; Double-Blind Method ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/metabolism ; *Macular Edema/drug therapy/metabolism ; *Diabetic Retinopathy/drug therapy/metabolism/physiopathology ; Middle Aged ; Wet Macular Degeneration/drug therapy/metabolism/physiopathology ; Aged, 80 and over ; },
abstract = {BACKGROUND: This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy.<br><br>METHODS: Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-na&#xef;ve nAMD patients. READ-3 enrolled treatment-na&#xef;ve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0&#x2009;mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0&#x2009;mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12.<br><br>MAIN OUTCOME MEASURE: association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA).<br><br>RESULTS: In both trials (HARBOR, N&#x2009;=&#x2009;36; READ-3, N&#x2009;=&#x2009;137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters.<br><br>CONCLUSIONS: Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO.},
}
@article {pmid38622152,
year = {2024},
author = {Tan, TF and Yap, CL and Peterson, CL and Wong, D and Wong, TY and Cheung, CMG and Schmetterer, L and Tan, ACS},
title = {Defining the structure-function relationship of specific lesions in early and advanced age-related macular degeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {8724},
pmid = {38622152},
issn = {2045-2322},
mesh = {Humans ; Cross-Sectional Studies ; Prospective Studies ; *Macular Degeneration/diagnostic imaging ; Tomography, Optical Coherence ; Fluorescein Angiography ; Structure-Activity Relationship ; },
abstract = {The objective of this study is to define structure-function relationships of pathological lesions related to age-related macular degeneration (AMD) using microperimetry and multimodal retinal imaging. We conducted a cross-sectional study of 87 patients with AMD (30 eyes with early and intermediate AMD and 110 eyes with advanced AMD), compared to 33 normal controls (66 eyes) recruited from a single tertiary center. All participants had enface and cross-sectional optical coherence tomography (Heidelberg HRA-2), OCT angiography, color and infra-red (IR) fundus and microperimetry (MP) (Nidek MP-3) performed. Multimodal images were graded for specific AMD pathological lesions. A custom marking tool was used to demarcate lesion boundaries on corresponding enface IR images, and subsequently superimposed onto MP color fundus photographs with retinal sensitivity points (RSP). The resulting overlay was used to correlate pathological structural changes to zonal functional changes. Mean age of patients with early/intermediate AMD, advanced AMD and controls were 73(SD = 8.2), 70.8(SD = 8), and 65.4(SD = 7.7) years respectively. Mean retinal sensitivity (MRS) of both early/intermediate (23.1 dB; SD = 5.5) and advanced AMD (18.1 dB; SD = 7.8) eyes were significantly worse than controls (27.8 dB, SD = 4.3) (p < 0.01). Advanced AMD eyes had significantly more unstable fixation (70%; SD = 63.6), larger mean fixation area (3.9 mm[2]; SD = 3.0), and focal fixation point further away from the fovea (0.7 mm; SD = 0.8), than controls (29%; SD = 43.9; 2.6 mm[2]; SD = 1.9; 0.4 mm; SD = 0.3) (p ≤ 0.01). Notably, 22 fellow eyes of AMD eyes (25.7 dB; SD = 3.0), with no AMD lesions, still had lower MRS than controls (p = 0.04). For specific AMD-related lesions, end-stage changes such as fibrosis (5.5 dB, SD = 5.4 dB) and atrophy (6.2 dB, SD = 7.0 dB) had the lowest MRS; while drusen and pigment epithelial detachment (17.7 dB, SD = 8.0 dB) had the highest MRS. Peri-lesional areas (20.2 dB, SD = 7.6 dB) and surrounding structurally normal areas (22.2 dB, SD = 6.9 dB) of the retina with no AMD lesions still had lower MRS compared to controls (27.8 dB, SD = 4.3 dB) (p < 0.01). Our detailed topographic structure-function correlation identified specific AMD pathological changes associated with a poorer visual function. This can provide an added value to the assessment of visual function to optimize treatment outcomes to existing and potentially future novel therapies.},
}
@article {pmid38622090,
year = {2024},
author = {Muraleva, NA and Zhdankina, AA and Fursova, AZ and Kolosova, NG},
title = {Retinoprotective Effect of SkQ1, Visomitin Eye Drops, Is Associated with Suppression of P38 MAPK and ERK1/2 Signaling Pathways Activity.},
journal = {Biochemistry. Biokhimiia},
volume = {89},
number = {2},
pages = {201-211},
doi = {10.1134/S0006297924020020},
pmid = {38622090},
issn = {1608-3040},
mesh = {Humans ; Rats ; Animals ; Infant ; Rats, Wistar ; *MAP Kinase Signaling System ; Ophthalmic Solutions/pharmacology ; p38 Mitogen-Activated Protein Kinases/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Aging/metabolism ; Signal Transduction ; *Benzalkonium Compounds ; Drug Combinations ; *Methylcellulose ; *Plastoquinone ; },
abstract = {Visomitin eye drops are the first and, so far, the only drug based on SkQ1 - the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl) decyltriphenylphosphonium, developed in the laboratories of Moscow State University under the leadership of Academician V. P. Skulachev. SkQ1 is considered as a potential tool to combat the aging program. We have previously shown that it is able to prevent and/or suppress development of all manifestations of accelerated senescence in OXYS rats, including retinopathy, similar to the age-related macular degeneration (AMD). Here, we assessed the effect of Visomitin instillations on progression of the AMD-like pathology and p38 MAPK and ERK1/2 activity in the OXYS rat retina (from the age of 9 to 12 months). Wistar and OXYS rats treated with placebo (composition identical to Visomitin with the exception of SkQ1) were used as controls. Ophthalmological examination showed that in the OXYS rats receiving placebo, retinopathy progressed and severity of clinical manifestations did not differ from the intact OXYS rats. Visomitin suppressed progression of the AMD-like pathology in the OXYS rats and significantly improved structural and functional parameters of the retinal pigment epithelium cells and state of microcirculation in the choroid, which, presumably, contributed to preservation of photoreceptors, associative and ganglion neurons. It was found that the activity of p38 MAPK and ERK1/2 in the retina of 12-month-old OXYS rats is higher than that of the Wistar rats of the same age, as indicated by the increased content of phosphorylated forms of p38 MAPK and ERK1/2 and their target protein tau (at position T181 and S396). Visomitin decreased phosphorylation of p38 MAPK, ERK1/2, and tau indicating suppression of activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress progression of the AMD-like pathology in the OXYS rats and their effect is associated with the decrease in activity of the MAPK signaling cascades.},
}
@article {pmid38621369,
year = {2024},
author = {Toto, L and Viggiano, P and Quarta, A and Grassi, M and De Nicola, C and Aloia, R and D'Aloisio, R and Boscia, G and Boscia, F and Porreca, A and Di Nicola, M and Savastano, MC and Mastropasqua, R},
title = {Effect of Pro Re Nata Regimen with Anti-VEGF on Type 3 Macular Neovascularization: Long-Term Outcomes.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {282-291},
doi = {10.1159/000538441},
pmid = {38621369},
issn = {1423-0259},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Intravitreal Injections ; *Visual Acuity ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Tomography, Optical Coherence/methods ; Follow-Up Studies ; Aged, 80 and over ; *Ranibizumab/administration &amp; dosage ; *Fluorescein Angiography/methods ; Macula Lutea/pathology ; Bevacizumab/administration &amp; dosage ; Treatment Outcome ; Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Fundus Oculi ; Time Factors ; Middle Aged ; },
abstract = {INTRODUCTION: The purpose of this study was to investigate long-term outcomes of intravitreal injections (IVI) of antivascular endothelial growth factor (VEGF) in neovascular age-related macular degeneration (nAMD) with type 3 macular neovascularization (MNV).<br><br>METHODS: This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and a PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT), and macular atrophy (MA) were assessed at baseline (T0) and during follow-up (T1, post-loading phase; T2, 1 year; T3, 2 years; T4 >2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analyzed. MA differences at T4 were assessed for pseudodrusen presence.<br><br>RESULTS: BCVA improved significantly during follow-up (p = 0.013) particularly increasing from baseline to post-loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward an increase in the post-loading phase that was not statistically significant (p = 0.082) and CT decreased significantly during follow-up (p < 0.001). MA changed significantly during follow-up (p < 0.001) with a significant increase from T0 to T3 and from T0 to T4 (p < 0.010). A Cochran-Armitage test for trend showed a significant reduction (p = 0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p = 0.040) and CT (p = 0.020). Indeed, the number of injections did not influence the change over time of MA (p = 0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p = 0.497).<br><br>CONCLUSIONS: Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.},
}
@article {pmid38619788,
year = {2024},
author = {Grassi, MO and Viggiano, P and Borrelli, E and Boscia, G and Molfetta, T and Malerba, MG and D'Addario, M and Giancipoli, E and Alessio, G and Boscia, F},
title = {Comparative Study on Anti-VEGF in Wet Age-Related Macular Degeneration in the Setting Based on Lean Methodology from the Bari Intravitreal Injection Registry (BIVIR).},
journal = {Ophthalmology and therapy},
volume = {13},
number = {6},
pages = {1619-1634},
pmid = {38619788},
issn = {2193-8245},
abstract = {INTRODUCTION: Optimizing treatment protocols for wet age-related macular degeneration (wAMD) is an ongoing challenge, as it involves a delicate balance between achieving therapeutic efficacy and minimizing invasive procedures' frequency. This study aimed to apply the Lean methodology and evaluate the effectiveness of this new setting on intravitreal therapy for wAMD, employing different anti-vascular endothelial growth factors (VEGF) drugs (bevacizumab, brolucizumab, aflibercept, ranibizumab), drawing data from the Bari Intravitreal Injections Registry (BIVIR).<br><br>METHODS: This was a retrospective, monocentric, nonrandomized, comparative study. Lean methodology was employed to design the new setting and the BIVIR collected information from electronic medical records. Clinical data of four groups, stratified based on the first-line anti-VEGF agents used, were compared. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes were compared between the four groups at 3 and 12 months.<br><br>RESULTS: Out of 4990 eyes and 41,323 intravitreal injections (IVs) recorded in BIVIR, 1421 eyes of 1182 patients were included. The mean number of IVs in first year was 6.1&#x2009;&#xb1;&#x2009;2.5, with no significant differences among the four subgroups. The mean change in BCVA was&#x2009;+&#x2009;6.2 letters [95% confidence interval (CI) 5.6-6.8] after two IVs, and&#x2009;+&#x2009;5.9 (95% CI 5.1-6.8) letters after three IVs; at three months, brolucizumab was associated with a greater mean increase in BCVA than bevacizumab (p&#x2009;=&#x2009;0.050); aflibercept (p&#x2009;=&#x2009;0.044) and ranibizumab p&#x2009;=&#x2009;0.047). At the 1-year follow-up, the mean change was&#x2009;+&#x2009;6.3 letters (95% CI 5.4-7.2), brolucizumab and ranibizumab were associated with a superior improvement in BCVA compared to aflibercept (p&#x2009;=&#x2009;0.033). Regarding the CRT, a significant reduction was observed in the subgroup treated with brolucizumab at the 3-month follow-up, compared to bevacizumab (p&#x2009;=&#x2009;0.003), aflibercept (p&#x2009;=&#x2009;0.015), and ranibizumab (p&#x2009;<&#x2009;0.001); Aflibercept exhibited a superior effect than ranibizumab (p&#x2009;=&#x2009;0.001). At 1-year follow-up, aflibercept resulted in a more significant reduction of macular thickness compared to ranibizumab (p&#x2009;=&#x2009;0.016) while no significant differences were observed among the other drugs.<br><br>CONCLUSIONS: Our practical experience showed the effectiveness of the new setting in the treatment of wAMD. This comparative study at 1&#xa0;year suggested a predominant brolucizumab efficacy on functional outcomes. In addition, brolucizumab and aflibercept appeared to have similar efficacy in fluid control.},
}
@article {pmid38617725,
year = {2024},
author = {Singh, P and Krishnaprasad, R and Ayachit, G and Joshi, S},
title = {Evaluation of clinical outcomes of raised intraocular pressure following intravitreal triamcinolone acetonide injection.},
journal = {Romanian journal of ophthalmology},
volume = {68},
number = {1},
pages = {37-44},
pmid = {38617725},
issn = {2501-2533},
mesh = {Humans ; Antiglaucoma Agents ; *Diabetic Retinopathy ; *Glaucoma ; *Glaucoma, Open-Angle ; Intraocular Pressure ; *Macular Degeneration ; *Macular Edema/diagnosis/drug therapy ; *Myopia ; Prospective Studies ; *Retinal Vein Occlusion ; Triamcinolone Acetonide ; Middle Aged ; Aged ; },
abstract = {Aim: To assess the incidence, risk factors, and treatment outcomes in intravitreal triamcinolone acetonide injection (IVTA) induced intraocular pressure rise and to compare IOP rise in 1-mg and 2-mg IVTA. Materials and methods: Prospective observational study conducted in all eyes receiving IVTA. Any pre-existing glaucoma and patients who received IVTA or dexamethasone implant in the last 6 months were excluded. Results: 9 between 61-70 years of age developed an IOP spike. The mean and standard deviation of age in years was 61.95 ± 8.70. Maximum eyes had ME due to Diabetic Retinopathy (53.3%). All cases of uveitic ME were reported to have an IOP spike. 2 out of 3 high myopic eyes and 1 eye with thyroid abnormality had an IOP spike. High IOP was found in 13 eyes, with more than 25 mm Hg rise in 4 eyes and more than 5 mm Hg rise from baseline IOP in 9 eyes. The mean and standard deviation of time taken for IOP raise (in days) was 46.39 ± 37.68. A total of 38 eyes received 1 mg of IVTA and the rest 22 received 2 mg of IVTA. 23.7% of 1 mg eyes experienced an IOP rise while it was 18.2% in eyes with 2 mg IVTA. The injection was repeated in 12 eyes and 41.7% developed an IOP spike among them. The independent "t" test results showed that there was a significant difference in the mean of IOP (Pre-injection) concerning the IOP rise (P=0.007*). 1 eye had IVTA crystals in the anterior chamber with raised IOP of 30 mm Hg. 1 out of 13 eyes with raised IOP needed 2 AGMs, the other 12 eyes responded well to 1 AGM. Discussion: IVTA is widely used in refractory cases of ME and steroid-induced glaucoma is the most common side effect of IVTA. To the best of our knowledge, there is a lack of literature on prospective studies on IVTA-associated risk factors, patterns of IOP elevation, and treatment outcomes. The pre-injection mean ± SD baseline IOP for uneventful eyes was 12.87±2.65 and the pre-injection mean IOP for eyes with IOP event was 15.23±2.89 (P=0.007*). Conclusion: We proposed that TA is an independent risk factor for post-intravitreal injection IOP spike. IVTA causes a maximum IOP spike at 1 to 2 months and has a protracted course that responds to anti-glaucoma medications. High baseline IOP, a repeated dose of IVTA, the presence of TA crystals in the anterior chamber, and high myopia were associated with significant IOP elevation. Abbreviations: ACD = Anterior chamber depth, AS = Anterior segment, AGM = Anti-glaucoma medications, ARMD = Age-related macular degeneration, BCVA = Best-corrected visual acuity, BRVO = Branch retinal vein occlusion, CCT = Central corneal thickness, CRVO = Central retinal vein occlusion, CME = Cystoid macular edema, CNVM = Choroidal neovascularization membrane, CSME = Clinically significant macular edema, DR = Diabetic retinopathy, ERM = Epiretinal membrane, IOP = Intraocular pressure, IGS = Irvine-Grass syndrome, GAGs = Glycosaminoglycans, IVTA = Intravitreal triamcinolone acetonide injection, ME = Macular edema, NVG = Neovascular glaucoma, OHT = Ocular hypertension, PDS = Pigment dispersion syndrome, PACG = Primary closed angle glaucoma, POAG = Primary open-angle glaucoma, PXF = Pseudoexfoliation, VA = Visual acuity, VEGF = Vascular endothelial growth factors, VH = Vonherick's grading, SD = Standard deviation, TA = Triamcinolone acetonide, TIGR = Trabecular meshwork inducible glucocorticoid response.},
}
@article {pmid38617724,
year = {2024},
author = {Hristova, R and Cholakova, D and Oscar, A and Wowra, B and Dzhelebov, D and Zdravkov, Y},
title = {Retropupillary Iris-fixated versus Sutured Scleral-fixated Intraocular Lenses.},
journal = {Romanian journal of ophthalmology},
volume = {68},
number = {1},
pages = {13-18},
pmid = {38617724},
issn = {2501-2533},
mesh = {Humans ; Prospective Studies ; *Lenses, Intraocular ; Iris/surgery ; Sclera/surgery ; *Aphakia ; },
abstract = {Aim: To compare the anatomical and functional results and patient satisfaction following retropupillary implantation of Artisan Aphakia iris-fixated intraocular lens (rAAIF) and sutured scleral fixated intraocular lens (SFIOL). Subjects and methods: We presented a prospective double-arm non-blinded study. Forty-one eyes with acquired aphakia, no age-related macular degeneration, no previous keratoplasty, no combined procedures, no AC reaction (cells, fibrin), normal intraocular pressure, no history of endothelial corneal dystrophy in relatives or fellow eye were included. Indications, complications, corrected distance visual acuity (CDVA), endothelial cell density (ECD), and patient satisfaction score were assessed. Results: Retropupillary AAIF was implanted in 21 (51.22%) eyes and SFIOL in 20 (48.78%) eyes. The most common indication was complicated cataract surgery in 18 cases (43.90%), followed by trauma in 16 (39.02%), and spontaneous dislocation in 7 (17.07%). No difference between rAAIF and SFIOL in terms of sex, laterality (χ=0.13, p=0.72), indications (χ=0.78, p=0.68), previous ocular history, and comorbidities was observed. The complications and the visual outcomes at 6 months postoperatively were similar between the two groups (p=0.95 and p=0.321, respectively). The ECD loss in the two groups was also similar (p=0.89). The patient satisfaction score was 58.67±8.80 in the rAAIF and 56.69±11.50 in the SFIOL group, which was statistically similar (p=0.764). Conclusion: Retropupillary AAIF and SFIOL showed similar results concerning visual acuity, endothelial cell loss, and patient satisfaction. Careful preoperative individual assessment is required to have optimal results with either technique. Abbreviations: AAIF = Artisan Aphakia iris-fixated intraocular lens, rAAIF = retropupillary Artisan Aphakia iris-fixated intraocular lens, CDVA = corrected distance visual acuity, ECD = endothelial cell density, IOL = intraocular lens, SD = standard deviation, SFIOL = scleral fixated intraocular lens.},
}
@article {pmid38615894,
year = {2024},
author = {Wei, D and Qu, C and Zhao, N and Li, S and Pu, N and Song, Z and Tao, Y},
title = {The significance of precisely regulating heme oxygenase-1 expression: Another avenue for treating age-related ocular disease?.},
journal = {Ageing research reviews},
volume = {97},
number = {},
pages = {102308},
doi = {10.1016/j.arr.2024.102308},
pmid = {38615894},
issn = {1872-9649},
mesh = {Humans ; *Heme Oxygenase-1/metabolism/genetics ; *Aging/metabolism/genetics ; *Eye Diseases/metabolism ; Animals ; Oxidative Stress/physiology ; },
abstract = {Aging entails the deterioration of the body's organs, including overall damages at both the genetic and cellular levels. The prevalence of age-related ocular disease such as macular degeneration, dry eye diseases, glaucoma and cataracts is increasing as the world's population ages, imposing a considerable economic burden on individuals and society. The development of age-related ocular disease is predominantly triggered by oxidative stress and chronic inflammatory reaction. Heme oxygenase-1 (HO-1) is a crucial antioxidant that mediates the degradative process of endogenous iron protoporphyrin heme. It catalyzes the rate-limiting step of the heme degradation reaction, and releases the metabolites such as carbon monoxide (CO), ferrous, and biliverdin (BV). The potent scavenging activity of these metabolites can help to defend against peroxides, peroxynitrite, hydroxyl, and superoxide radicals. Other than directly decomposing endogenous oxidizing substances (hemoglobin), HO-1 is also a critical regulator of inflammatory cells and tissue damage, exerting its anti-inflammation activity through regulating complex inflammatory networks. Therefore, promoting HO-1 expression may act as a promising therapeutic strategy for the age-related ocular disease. However, emerging evidences suggest that the overexpression of HO-1 significantly contributes to ferroptosis due to its dual nature. Surplus HO-1 leads to excessive Fe[2+] and reactive oxygen species, thereby causing lipid peroxidation and ferroptosis. In this review, we elucidate the role of HO-1 in countering age-related disease, and summarize recent pharmacological trials that targeting HO-1 for disease management. Further refinements of the knowledge would position HO-1 as a novel therapeutic target for age-related ocular disease.},
}
@article {pmid38615832,
year = {2024},
author = {Cakir Ince, BA and Kucukevcilioglu, M and Yucel, C and Durukan, AH},
title = {Examining the correlation of lymphangiogenesis biomarkers with clinical condition in Age-Related Macular Degeneration (AMD).},
journal = {Experimental eye research},
volume = {243},
number = {},
pages = {109891},
doi = {10.1016/j.exer.2024.109891},
pmid = {38615832},
issn = {1096-0007},
mesh = {Humans ; *Lymphangiogenesis ; Male ; Female ; *Biomarkers/metabolism/blood ; Prospective Studies ; Aged ; *Vascular Endothelial Growth Factor Receptor-3/metabolism ; *Vascular Endothelial Growth Factor C/metabolism/blood ; *Aqueous Humor/metabolism ; *Enzyme-Linked Immunosorbent Assay ; *Vitreous Body/metabolism/pathology ; *Membrane Glycoproteins/metabolism ; *Vesicular Transport Proteins/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Middle Aged ; Aged, 80 and over ; Macular Degeneration/metabolism/diagnosis ; Wet Macular Degeneration/metabolism/diagnosis ; },
abstract = {The aim of this study is to investigate the relationship between age-related macular degeneration (AMD) and lymphangiogenesis biomarkers, namely LYVE-1, Podoplanin, VEGF-C, VEGFR-2 and VEGFR-3. This prospective and interventional study includes 30 patients with AMD which may be dry or wet type and 30 controls for whom vitrectomy and phacoemulsification was indicated due to additional pathologies (epiretinal membrane, macular hole, retinal detachment, and cataract). 0.1-0,2 ml of aqueous humor and 0.5-1 ml of vitreous sample was taken during the operations. Before the operations 1 tube serum was also taken. All the lymphangiogenesis biomarkers in the study are examined by ELISA method. LYVE-1 (p = 0.001) and Podoplanin (p = 0.004) levels in the vitreous for the patient group are found to be significantly lower than the control group. Serum (p = 0.019), vitreous (p = 0.001), aqueous (p < 0.001) levels of VEGF-C for the patient group are significantly higher than the control group. VEGF-C/VEGFR-2 (p < 0.001), VEGF-C/VEGFR-3 (p < 0.001) ratios in the vitreous for the patient group are found to be significantly higher than the control group. Especially in wet AMD patients, LYVE-1 level is significantly lower in the vitreous (p = 0.002) and aqueous (p = 0.002) than the control group. In addition, Podoplanin level is observed as significantly lower in the vitreous (p = 0.014) and serum (p = 0.002) in comparison to control group. In the wet AMD group, VEGF-C level in the vitreous (p < 0.001), aqueous (p < 0.001) and serum (p = 0.001) is higher than the control group. The result of this study indicates a valid relationship between the weakening of lymphangiogenesis and the pathophysiology of AMD, especially for the wet type. It is observed that the levels of receptors that bind VEGF-C (VEGFR-2 and VEGFR-3) do not increase at the same rate as VEGF-C to compensate for the increase in VEGF-C. The absence of an increase in VEGFR-3, which is especially necessary for lymphangiogenesis, also suggests that lymphangiogenesis is weakened or decreased in AMD. In the future interventional studies with larger series, examination of lymphangiogenic biomarkers in inflammatory retinal diseases and glaucoma may reveal unexplored details.},
}
@article {pmid38612907,
year = {2024},
author = {Brito, M and Sorbier, C and Mignet, N and Boudy, V and Borchard, G and Vacher, G},
title = {Understanding the Impact of Polyunsaturated Fatty Acids on Age-Related Macular Degeneration: A Review.},
journal = {International journal of molecular sciences},
volume = {25},
number = {7},
pages = {},
pmid = {38612907},
issn = {1422-0067},
mesh = {Humans ; Fatty Acids, Unsaturated/therapeutic use ; *Wet Macular Degeneration ; Fatty Acids ; *Fatty Acids, Omega-3/therapeutic use ; *Geographic Atrophy ; },
abstract = {Age-related Macular Degeneration (AMD) is a multifactorial ocular pathology that destroys the photoreceptors of the macula. Two forms are distinguished, dry and wet AMD, with different pathophysiological mechanisms. Although treatments were shown to be effective in wet AMD, they remain a heavy burden for patients and caregivers, resulting in a lack of patient compliance. For dry AMD, no real effective treatment is available in Europe. It is, therefore, essential to look for new approaches. Recently, the use of long-chain and very long-chain polyunsaturated fatty acids was identified as an interesting new therapeutic alternative. Indeed, the levels of these fatty acids, core components of photoreceptors, are significantly decreased in AMD patients. To better understand this pathology and to evaluate the efficacy of various molecules, in vitro and in vivo models reproducing the mechanisms of both types of AMD were developed. This article reviews the anatomy and the physiological aging of the retina and summarizes the clinical aspects, pathophysiological mechanisms of AMD and potential treatment strategies. In vitro and in vivo models of AMD are also presented. Finally, this manuscript focuses on the application of omega-3 fatty acids for the prevention and treatment of both types of AMD.},
}
@article {pmid38612812,
year = {2024},
author = {Romeo, A and Kazsoki, A and Musumeci, T and Zelkó, R},
title = {A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders-A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {25},
number = {7},
pages = {},
pmid = {38612812},
issn = {1422-0067},
mesh = {*Melatonin/therapeutic use/pharmacology ; Humans ; *Eye Diseases/drug therapy ; Animals ; Antioxidants/therapeutic use/pharmacology/chemistry ; Drug Compounding ; },
abstract = {Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.},
}
@article {pmid38612560,
year = {2024},
author = {Ahluwalia, K and Du, Z and Martinez-Camarillo, JC and Naik, A and Thomas, BB and Pollalis, D and Lee, SY and Dave, P and Zhou, E and Li, Z and Chester, C and Humayun, MS and Louie, SG},
title = {Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights.},
journal = {International journal of molecular sciences},
volume = {25},
number = {7},
pages = {},
pmid = {38612560},
issn = {1422-0067},
support = {P30 EY029220/EY/NEI NIH HHS/United States ; P30EY029220/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Adult ; Animals ; Rats ; *Retinal Degeneration ; *Macular Degeneration ; *Retinitis Pigmentosa ; *Surgeons ; Retina ; },
abstract = {Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development.},
}
@article {pmid38611684,
year = {2024},
author = {Sendecki, A and Ledwoń, D and Tuszy, A and Nycz, J and Wąsowska, A and Boguszewska-Chachulska, A and Wylęgała, A and Mitas, AW and Wylęgała, E and Teper, S},
title = {Association of Genetic Risk for Age-Related Macular Degeneration with Morphological Features of the Retinal Microvascular Network.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {7},
pages = {},
pmid = {38611684},
issn = {2075-4418},
support = {STRATEGMED1/234261/2/NCBR/2014//National Centre for Research and Development/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial disease encompassing a complex interaction between aging, environmental risk factors, and genetic susceptibility. The study aimed to determine whether there is a relationship between the polygenic risk score (PRS) in patients with AMD and the characteristics of the retinal vascular network visualized by optical coherence tomography angiography (OCTA).<br><br>METHODS: 235 patients with AMD and 97 healthy controls were included. We used data from a previous AMD PRS study with the same group. The vascular features from different retina layers were compared between the control group and the patients with AMD. The association between features and PRS was then analyzed using univariate and multivariate approaches.<br><br>RESULTS: Significant differences between the control group and AMD patients were found in the vessel diameter distribution (variance: p = 0.0193, skewness: p = 0.0457) and fractal dimension distribution (mean: p = 0.0024, variance: p = 0.0123). Both univariate and multivariate analyses showed no direct and significant association between the characteristics of the vascular network and AMD PRS.<br><br>CONCLUSIONS: The vascular features of the retina do not constitute a biomarker of the risk of AMD. We have not identified a genotype-phenotype relationship, and the expression of AMD-related genes is perhaps not associated with the characteristics of the retinal vascular network.},
}
@article {pmid38611681,
year = {2024},
author = {Gofas-Salas, E and Lee, DMW and Rondeau, C and Grieve, K and Rossi, EA and Paques, M and Gocho, K},
title = {Comparison between Two Adaptive Optics Methods for Imaging of Individual Retinal Pigmented Epithelial Cells.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {7},
pages = {},
pmid = {38611681},
issn = {2075-4418},
support = {R01 EY030517/EY/NEI NIH HHS/United States ; R01030517/EY/NEI NIH HHS/United States ; },
abstract = {The Retinal Pigment Epithelium (RPE) plays a prominent role in diseases such as age-related macular degeneration, but imaging individual RPE cells is challenging due to their high absorption and low autofluorescence emission. The RPE lies beneath the highly reflective photoreceptor layer (PR) and contains absorptive pigments, preventing direct backscattered light detection when the PR layer is intact. Here, we used near-infrared autofluorescence adaptive optics scanning laser ophthalmoscopy (NIRAF AOSLO) and transscleral flood imaging (TFI) in the same healthy eyes to cross-validate these approaches. Both methods revealed a consistent RPE mosaic pattern and appeared to reflect a distribution of fluorophores consistent with findings from histological studies. Interestingly, even in apparently healthy RPE, we observed dynamic changes over months, suggesting ongoing cellular activity or alterations in fluorophore distribution. These findings emphasize the value of NIRAF AOSLO and TFI in understanding RPE morphology and dynamics.},
}
@article {pmid38611677,
year = {2024},
author = {Iliescu, DA and Ghita, AC and Ilie, LA and Voiculescu, SE and Geamanu, A and Ghita, AM},
title = {Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {7},
pages = {},
pmid = {38611677},
issn = {2075-4418},
abstract = {The imagistic evaluation of non-neovascular age-related macular degeneration (AMD) is crucial for diagnosis, monitoring progression, and guiding management of the disease. Dry AMD, characterized primarily by the presence of drusen and retinal pigment epithelium atrophy, requires detailed visualization of the retinal structure to assess its severity and progression. Several imaging modalities are pivotal in the evaluation of non-neovascular AMD, including optical coherence tomography, fundus autofluorescence, or color fundus photography. In the context of emerging therapies for geographic atrophy, like pegcetacoplan, it is critical to establish the baseline status of the disease, monitor the development and expansion of geographic atrophy, and to evaluate the retina's response to potential treatments in clinical trials. The present review, while initially providing a comprehensive description of the pathophysiology involved in AMD, aims to offer an overview of the imaging modalities employed in the evaluation of non-neovascular AMD. Special emphasis is placed on the assessment of progression biomarkers as discerned through optical coherence tomography. As the landscape of AMD treatment continues to evolve, advanced imaging techniques will remain at the forefront, enabling clinicians to offer the most effective and tailored treatments to their patients.},
}
@article {pmid38611667,
year = {2024},
author = {Ra, H and Jung, Y and Lee, SH and Park, SW and Chhablani, J and Baek, J},
title = {Quantification of Choroidal Vascular Hyperpermeability on Ultra-Widefield Indocyanine Green Angiography in Macular Neovascularization.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {7},
pages = {},
pmid = {38611667},
issn = {2075-4418},
support = {NRF001663041G0003101//Korean government (MSIT)/ ; },
abstract = {To obtain a quantitative parameter for the measurement of choroidal vascular hyperpermeability (CVH) on ultra-widefield indocyanine green angiography (UWICGA) using an objective analysis method in macular choroidal neovascularization (CNV). A total of 113 UWICGA images from 113 subjects were obtained, including with 25 neovascular age-related macular degeneration (nAMD), 37 with polypoidal choroidal vasculopathy (PCV) (19 with thin-choroid and 18 with thick-choroid), 33 with pachychoroid neovasculopathy (PNV), and 18 age-matched controls. CVH was quantified on a gray image by the subtraction of 2 synchronized UWICGA images of early and late phases. The measured CVH parameter was compared with human graders and among CNV subtypes and correlated with choroidal vascular density (CVD) and subfoveal choroidal thickness (SFCT). The mean CVH values were 28.58 ± 4.97, 33.36 ± 8.40, 33.61 ± 11.50, 42.19 ± 13.25, and 43.59 ± 7.86 in controls and patients with nAMD, thin-choroid PCV, thick-choroid PCV, and PNV, respectively (p < 0.001). CVH was higher in thick-choroid PCV and PNV compared to the other groups (all p ≤ 0.006). The measured CVH value positively correlated with those reported by human graders (p < 0.001), CVD, and SFCT (p = 0.001 and p < 0.001, respectively). CVH can be measured objectively using quantitative UWICGA analysis. The CVH parameter differs among macular CNV subtypes and correlates with CVD and SFCT.},
}
@article {pmid38608232,
year = {2024},
author = {Husain, S and Obert, E and Singh, S and Schnabolk, G},
title = {Inhibition of HDAC1 and 3 in the Presence of Systemic Inflammation Reduces Retinal Degeneration in a Model of Dry Age-Related Macular Degeneration.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {40},
number = {6},
pages = {397-406},
pmid = {38608232},
issn = {1557-7732},
support = {R01 EY034514/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Mice, Inbred C57BL ; Mice ; *Histone Deacetylase Inhibitors/pharmacology/administration &amp; dosage/therapeutic use ; *Disease Models, Animal ; *Inflammation/drug therapy ; *Iodates/administration &amp; dosage/toxicity ; *Pyridines/pharmacology/administration &amp; dosage/therapeutic use ; *Histone Deacetylase 1/antagonists &amp; inhibitors/metabolism ; *Tomography, Optical Coherence ; Benzamides/pharmacology/administration &amp; dosage/therapeutic use ; Histone Deacetylases/metabolism ; Retinal Degeneration/drug therapy/pathology ; Macular Degeneration/drug therapy/pathology ; Male ; Electroretinography ; Pyridinium Compounds/pharmacology/administration &amp; dosage ; Geographic Atrophy/drug therapy ; },
abstract = {Purpose: Previously, we identified increased retinal degeneration and cytokine response in a mouse model of dry age-related macular degeneration (AMD) in the presence of systemic inflammation from rheumatoid arthritis (RA). Histone deacetylases (HDACs) regulate cytokine production by reducing acetylation and are found to be dysregulated in inflammatory diseases, including RA and AMD. Therefore, this current study investigates the effect of HDAC inhibition on AMD progression in the presence of systemic inflammation. Methods: Collagen induced arthritis (CIA) was induced in C57BL6J mice, followed by sodium iodate (NaIO3)-induced retinal degeneration. Mice were treated with a selective HDAC class I inhibitor, MS-275, and retinal structure [optical coherence tomography (OCT)], function (electroretinography), and molecular changes quantitative real-time polymerase chain reaction (RT-qPCR, Western Blot) were assessed. Results: NaIO3 retinal damage was diminished in CIA mice treated with MS-275 (P ≤ 0.05). While no significant difference was observed in retinal pigment epithelium (RPE) function, a trend in increased c-wave amplitude was detected in CIA + NaIO3 mice treated with MS-275. Finally, we identified decreased Hdac1, Hdac3, and Cxcl9 expression in CIA + NaIO3 mouse RPE/choroid when treated with MS-275 (P ≤ 0.05). Conclusions: Our data demonstrate that HDAC inhibition can reduce the additive effect of NaIO3-induced retinal degeneration in the presence of systemic inflammation by CIA as measured by OCT analysis. In addition, HDAC inhibition in CIA + NaIO3 treated mice resulted in reduced cytokine production. These findings are highly innovative and provide additional support to the therapeutic potential of HDAC inhibitors for dry AMD treatment.},
}
@article {pmid38608102,
year = {2024},
author = {Zhang, M and Duan, L and Feng, Y},
title = {Causal association between rheumatoid arthritis and an increased risk of age-related macular degeneration: A Mendelian randomization study.},
journal = {Medicine},
volume = {103},
number = {15},
pages = {e37753},
pmid = {38608102},
issn = {1536-5964},
mesh = {Humans ; Mendelian Randomization Analysis ; *Arthritis, Rheumatoid/complications/genetics ; Causality ; Databases, Factual ; *Macular Degeneration/epidemiology/genetics ; },
abstract = {This study's goal is to evaluate if there is a causal connection between rheumatoid arthritis (RA) and age-related macular degeneration (AMD), despite past epidemiological studies suggesting an association between the 2 disorders. The impact of RA on AMD is still unknown. Mendelian randomization (MR) was utilized in this study to assess the two-sample causal relationship between RA and AMD. Summary data from GWAS for RA and AMD in individuals with all European ancestries were gathered using the IEU GWAS database. The GWAS summary statistics of RA (14,361 RA patients and 43,923 healthy controls) and AMD (14,034 AMD patients and 91,214 controls participated) were obtained from the IEU GWAS database. After identifying suitable instrumental variables in line with the 3 MR assumptions, we conducted MR using the Mendelian randomization-Egger (MR-Egger), weighted median, and inverse variance weighting techniques. The MR-Egger intercept and MR-Polyvalent Residuals and Outliers methods were used to investigate the effects of horizontal pleiotropy. The leave-one-out strategy was used to prevent bias caused by certain single nucleotide polymorphisms. Sensitivity analysis was used to detect the heterogeneity. Using 50 single nucleotide polymorphisms as instrumental variables, this study examined the relationship between RA and AMD and discovered that RA increased the risk of AMD (inverse variance weighting odds ratio [OR] = 1.056, 95% confidence interval [CI] = 1.02-1.09, P = 5.44E-04; weighted median OR = 1.085, 95% CI = 1.04-1.14, P = 4.05E-04; MR-Egger OR = 1.074, 95% CI = 1.01-1.14, P = 2.18E-2). The current investigation demonstrated a causal link between AMD and RA. RA increased the risk of AMD. It is advised that future research concentrate on the processes underlying the relationship between RA and AMD.},
}
@article {pmid38607409,
year = {2024},
author = {Aljundi, W and Munteanu, C and Seitz, B and Abdin, AD},
title = {Short-term outcomes of intravitreal faricimab for refractory neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {9},
pages = {2867-2874},
pmid = {38607409},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Intravitreal Injections ; *Visual Acuity ; Aged ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; *Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; *Fluorescein Angiography ; Time Factors ; Macula Lutea/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fundus Oculi ; Aged, 80 and over ; },
abstract = {PURPOSE: To assess the short-term outcomes of intravitreal faricimab (IVF) for previously treated refractory neovascular age-related macular degeneration (nAMD) in a real-world setting.<br><br>METHODS: A retrospective monocentric study including 44 eyes treated with an upload of 4&#x2009;&#xd7;&#x2009;monthly intravitreal injections (IVI) of faricimab 6 mg/0.05 mL and followed for 4 weeks after last IVI (16 W). Patients were switched to IVF after treatment with at least three other anti-vascular endothelial growth factors (anti-VEGF). Main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and retinal fluid distribution.<br><br>RESULTS: 44 eyes of 44 patients with previously treated refractory nAMD (63% males) were included. Mean age was 79&#x2009;&#xb1;&#x2009;7 years. The total number of previous anti-VEGF before switching to IVF was 32&#x2009;&#xb1;&#x2009;15 IVIs/eye. BCVA (logMAR) improved significantly from 0.65&#x2009;&#xb1;&#x2009;0.26 to 0.50&#x2009;&#xb1;&#x2009;0.23 at 16 W (p&#x2009;< 0.01). CMT (&#xb5;m) decreased significantly from 422&#x2009;&#xb1;&#x2009;68 to 362&#x2009;&#xb1;&#x2009;47 at 16 W (p&#x2009;<&#x2009;0.01). SFCT did not change significantly at 16 W (p&#x2009;=&#x2009;0.06). The number of eyes with subretinal fluid (SRF) decreased significantly from 29 (65%) to 13 (29%) at 16 W (p&#x2009;=&#x2009;0.001). There were no significant changes regarding the distribution of intraretinal fluid or pigment epithelial detachment (p&#x2009;>&#x2009;0.05). A complete fluid resolution was achieved in 8 eyes (18%). No adverse events were noticed.<br><br>CONCLUSION: In the short term, IVF led to a significant decrease in CMT as well as a significant improvement of BCVA and thus appears to be an effective treatment option for previously treated refractory nAMD without relevant adverse effects.},
}
@article {pmid38607040,
year = {2024},
author = {Suárez-Herrera, N and Li, CHZ and Leijsten, N and Karjosukarso, DW and Corradi, Z and Bukkems, F and Duijkers, L and Cremers, FPM and Hoyng, CB and Garanto, A and Collin, RWJ},
title = {Preclinical Development of Antisense Oligonucleotides to Rescue Aberrant Splicing Caused by an Ultrarare ABCA4 Variant in a Child with Early-Onset Stargardt Disease.},
journal = {Cells},
volume = {13},
number = {7},
pages = {},
pmid = {38607040},
issn = {2073-4409},
support = {PPA-0517-0717-RAD/FFB/Foundation Fighting Blindness/United States ; TA-GT-0521-0799-RAD-TRAP/FFB/Foundation Fighting Blindness/United States ; },
mesh = {Humans ; Female ; Child ; Stargardt Disease/genetics ; *Oligonucleotides, Antisense/pharmacology/therapeutic use ; HEK293 Cells ; Introns ; *ATP-Binding Cassette Transporters/genetics ; },
abstract = {Precision medicine is rapidly gaining recognition in the field of (ultra)rare conditions, where only a few individuals in the world are affected. Clinical trial design for a small number of patients is extremely challenging, and for this reason, the development of N-of-1 strategies is explored to accelerate customized therapy design for rare cases. A strong candidate for this approach is Stargardt disease (STGD1), an autosomal recessive macular degeneration characterized by high genetic and phenotypic heterogeneity. STGD1 is caused by pathogenic variants in ABCA4, and amongst them, several deep-intronic variants alter the pre-mRNA splicing process, generally resulting in the insertion of pseudoexons (PEs) into the final transcript. In this study, we describe a 10-year-old girl harboring the unique deep-intronic ABCA4 variant c.6817-713A>G. Clinically, she presents with typical early-onset STGD1 with a high disease symmetry between her two eyes. Molecularly, we designed antisense oligonucleotides (AONs) to block the produced PE insertion. Splicing rescue was assessed in three different in vitro models: HEK293T cells, fibroblasts, and photoreceptor precursor cells, the last two being derived from the patient. Overall, our research is intended to serve as the basis for a personalized N-of-1 AON-based treatment to stop early vision loss in this patient.},
}
@article {pmid38606038,
year = {2024},
author = {Gomi, F and Kawasaki, R and Ogura, Y and Iwasaki, K and Takeshima, T and Yamabe, M and Imai, K},
title = {Patterns of anti-vascular endothelial growth factor treatment for chorioretinal vascular diseases: Analysis of a nationwide claims database in Japan.},
journal = {Annals of clinical epidemiology},
volume = {6},
number = {2},
pages = {42-50},
pmid = {38606038},
issn = {2434-4338},
abstract = {BACKGROUND: Although intravitreal anti-vascular endothelial growth factor therapy is currently considered the first-line treatment for chorioretinal vascular diseases in Japan, information regarding its treatment pattern is scarce. This study investigated the patterns of anti-vascular endothelial growth factor treatment for chorioretinal vascular diseases.<br><br>METHODS: A health insurance claims database from acute care hospitals was used to estimate treatment intervals and continuation and drop-out rates regarding the anti-vascular endothelial growth factor. Patients aged &#x2265;50 years diagnosed with neovascular age-related macular degeneration or aged &#x2265;18 years diagnosed with diabetic macular edema or retinal vein occlusion were analyzed.<br><br>RESULTS: Data were included for 76,535, 49,704, and 37,681 patients with neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively; exactly 8,111, 2,283, and 6,896 received the treatment, respectively. The mean and median interval ranges during the maintenance phase by treatment initiation year were 94-100 and 73-80, 111-120 and 98-102, and 97-103 and 87-93 days for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively, without any trend over time. A tendency to increase the treatment continuation rate was indicated in later years by Kaplan-Meier curves. The drop-out rate in the treatment initiation year (2016) was 32% from 63% (2009), 53% from 69% (2014), and 36% from 47% (2013) for neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion, respectively.<br><br>CONCLUSIONS: For all these diseases, the treatment intervals did not change remarkably, and a tendency toward improved treatment continuation was suggested.},
}
@article {pmid38605811,
year = {2024},
author = {Haldrup, SH and Fabian-Jessing, BK and Jakobsen, TS and Lindholm, AB and Adsersen, RL and Aagaard, L and Bek, T and Askou, AL and Corydon, TJ},
title = {Subretinal AAV delivery of RNAi-therapeutics targeting VEGFA reduces choroidal neovascularization in a large animal model.},
journal = {Molecular therapy. Methods &amp; clinical development},
volume = {32},
number = {2},
pages = {101242},
pmid = {38605811},
issn = {2329-0501},
abstract = {Neovascular age-related macular degeneration (nAMD) is a frequent cause of vision loss among the elderly in the Western world. Current disease management with repeated injections of anti-VEGF agents accumulates the risk for adverse events and constitutes a burden for society and the individual patient. Sustained suppression of VEGF using gene therapy is an attractive alternative, which we explored using adeno-associated virus (AAV)-based delivery of novel RNA interference (RNAi) effectors in a porcine model of choroidal neovascularization (CNV). The potency of VEGFA-targeting, Ago2-dependent short hairpin RNAs placed in pri-microRNA scaffolds (miR-agshRNA) was established in vitro and in vivo in mice. Subsequently, AAV serotype 8 (AAV2.8) vectors encoding VEGFA-targeting or irrelevant miR-agshRNAs under the control of a tissue-specific promotor were delivered to the porcine retina via subretinal injection before CNV induction by laser. Notably, VEGFA-targeting miR-agshRNAs resulted in a significant and sizable reduction of CNV compared with the non-targeting control. We also demonstrated that single-stranded and self-complementary AAV2.8 vectors efficiently transduce porcine retinal pigment epithelium cells but differ in their transduction characteristics and retinal safety. Collectively, our data demonstrated a robust anti-angiogenic effect of VEGFA-targeting miR-aghsRNAs in a large translational animal model, thereby suggesting AAV-based delivery of anti-VEGFA RNAi therapeutics as a valuable tool for the management of nAMD.},
}
@article {pmid38605245,
year = {2024},
author = {Kruper, J and Richie-Halford, A and Benson, NC and Caffarra, S and Owen, J and Wu, Y and Egan, C and Lee, AY and Lee, CS and Yeatman, JD and Rokem, A and , },
title = {Convolutional neural network-based classification of glaucoma using optic radiation tissue properties.},
journal = {Communications medicine},
volume = {4},
number = {1},
pages = {72},
pmid = {38605245},
issn = {2730-664X},
support = {RF1 MH121868/MH/NIMH NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; K23 EY029246/EY/NEI NIH HHS/United States ; R01 EY033628/EY/NEI NIH HHS/United States ; U19 AG066567/AG/NIA NIH HHS/United States ; R01 EB027585/EB/NIBIB NIH HHS/United States ; R01 HD095861/HD/NICHD NIH HHS/United States ; },
abstract = {BACKGROUND: Sensory changes due to aging or disease can impact brain tissue. This study aims to investigate the link between glaucoma, a leading cause of blindness, and alterations in brain connections.<br><br>METHODS: We analyzed diffusion MRI measurements of white matter tissue in a large group, consisting of 905 glaucoma patients (aged 49-80) and 5292 healthy individuals (aged 45-80) from the UK Biobank. Confounds due to group differences were mitigated by matching a sub-sample of controls to glaucoma subjects. We compared classification of glaucoma using convolutional neural networks (CNNs) focusing on the optic radiations, which are the primary visual connection to the cortex, against those analyzing non-visual brain connections. As a control, we evaluated the performance of regularized linear regression models.<br><br>RESULTS: We showed that CNNs using information from the optic radiations exhibited higher accuracy in classifying subjects with glaucoma when contrasted with CNNs relying on information from non-visual brain connections. Regularized linear regression models were also tested, and showed significantly weaker classification performance. Additionally, the CNN was unable to generalize to the classification of age-group or of age-related macular degeneration.<br><br>CONCLUSIONS: Our findings indicate a distinct and potentially non-linear signature of glaucoma in the tissue properties of optic radiations. This study enhances our understanding of how glaucoma affects brain tissue and opens avenues for further research into how diseases that affect sensory input may also affect brain aging.},
}
@article {pmid38605088,
year = {2024},
author = {Kulyabin, M and Zhdanov, A and Nikiforova, A and Stepichev, A and Kuznetsova, A and Ronkin, M and Borisov, V and Bogachev, A and Korotkich, S and Constable, PA and Maier, A},
title = {OCTDL: Optical Coherence Tomography Dataset for Image-Based Deep Learning Methods.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {365},
pmid = {38605088},
issn = {2052-4463},
mesh = {Humans ; *Deep Learning ; Diabetic Retinopathy/diagnostic imaging ; Macular Edema/diagnostic imaging ; *Retina/diagnostic imaging ; *Tomography, Optical Coherence ; *Retinal Diseases/diagnostic imaging ; },
abstract = {Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 2000 OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.},
}
@article {pmid38605074,
year = {2024},
author = {Ebrahimi, M and Sivaprasad, S},
title = {The potential effects of newer groups of glucose lowering drugs on age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {13},
pages = {2649-2650},
pmid = {38605074},
issn = {1476-5454},
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Hypoglycemic Agents/therapeutic use/adverse effects ; },
}
@article {pmid38603895,
year = {2024},
author = {Niegowski, LJ and Cohen, SY and Crincoli, E and Mehanna, CJ and Souied, EH},
title = {Cognitive bias evaluation on the choice of treatment in common retinal disorders among retina specialists in 2023.},
journal = {Journal francais d'ophtalmologie},
volume = {47},
number = {6},
pages = {104177},
doi = {10.1016/j.jfo.2024.104177},
pmid = {38603895},
issn = {1773-0597},
mesh = {Humans ; Male ; *Ophthalmologists/statistics &amp; numerical data ; *Retinal Diseases/drug therapy/epidemiology/therapy ; Female ; *Practice Patterns, Physicians'/statistics &amp; numerical data/standards ; France/epidemiology ; Middle Aged ; Surveys and Questionnaires ; Angiogenesis Inhibitors/administration &amp; dosage ; Adult ; Ophthalmology/statistics &amp; numerical data/standards ; Retinal Vein Occlusion/drug therapy/complications/epidemiology ; },
abstract = {PURPOSE: The study aimed to discern the intent to treat with the therapeutic agents prescribed first or second line in the following eye conditions: neovascular age-related macular Degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic maculopathy with choroidal neovascularization (MMNV). The study also aimed to distinguish the ophthalmologists' intended treatment for their patients from those that they would prescribe for themselves if they were affected by the above macular conditions.<br><br>METHODS: The study utilized an online survey of 243 French ophthalmologists practicing medical retina, with males accounting for 54.3% of the participants. Data was obtained using a questionnaire that focused on the ophthalmologists' experience with various agents as well as their first and second line choices for nAMD, DME, RVO, and MMNV.<br><br>RESULTS: The vast majority of French ophthalmologists (99%) had experience with the most widely used anti-vascular endothelial growth factors (anti-VEGFs); ranibizumab, bevacizumab, and aflibercept. Fewer than 8% reported experience with anti-VEGF drug reservoirs, biosimilars, or faricimab. The study findings also showed ranibizumab and aflibercept as the commonly prescribed first line choices for the above-mentioned ocular conditions. For the second line choice, the study showed that aflibercept and dexamethasone intravitreal implants were the most common across the four retinal conditions studied. The only difference in intent to treat for "patients" versus "yourself" was for biosimilars (0% to 0.8%, P=0.001).<br><br>CONCLUSION: The findings regarding the first and second line choices for the mentioned ocular disorders were found to agree with the findings of published literature currently used in practice, with a tendency to prefer ranibizumab as first line therapy for neovascular disorders and aflibercept as first line therapy for macular edema. In addition, there were no differences between choices for first and second line therapy for patients vs. ophthalmologists.},
}
@article {pmid38601051,
year = {2023},
author = {Vukojevic, A and Vukojevic, M and Jukic, T and Petricek, I and Mandic, K and Vukojevic, N},
title = {Pseudovitelliform maculopathy associated with hereditary hemochromatosis.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {12},
number = {4},
pages = {203-212},
pmid = {38601051},
issn = {2322-3219},
abstract = {BACKGROUND: Hereditary hemochromatosis (HH) is an inherited autosomal recessive iron metabolism disorder resulting from a C282Y mutation in the HFE gene. Mutations in the HFE gene may result in iron accumulation and oxidative stress in the retina, resulting in macular degeneration. This article describes two patients with HH who were treated with erythrocytapheresis or phlebotomy, with no exposure to deferoxamine or any other chelation therapy, and who developed visual symptoms.<br><br>CASE PRESENTATION: Both patients had known diagnoses of HH. Because of visual symptoms, they were referred to the ophthalmology clinic and underwent a retinal exam, multimodal imaging, and electrodiagnostic studies, which revealed structural and functional degeneration of the central macula. Fundus photography, fluorescein angiography, and fundus autofluorescence revealed changes at the level of the retinal pigment epithelium (RPE) in the central macula. In addition, optical coherence tomography revealed subfoveal accumulation of hyperreflective material at and below the RPE. Multifocal electroretinography confirmed a decreased cone response, whereas the full-field electroretinogram was unremarkable. Genetic testing ruled out Best's vitelliform macular dystrophy and the other known hereditary macular dystrophies. The patients had known diagnoses of HH, homozygous C282Y mutations in the HFE gene, and no comorbidities; thus, we presumed that HH led to the observed morphological and functional disorders of the RPE, which in turn caused structural macular changes in both patients.<br><br>CONCLUSIONS: Considering the macular findings and the nature of the patients' primary illness, we believe that the accumulation of iron and photoreceptor metabolic products caused dysfunction in the RPE, which led to morphological and functional changes in the macula. Because the patients were not treated using chelating agents, we attribute the macular changes solely to iron accumulation and oxidative stress caused by the pathophysiological processes of HH. Further studies are needed to identify the plausible molecular or cellular insults underlying pseudovitelliform macular degeneration in patients with HH.},
}
@article {pmid38601018,
year = {2024},
author = {Betts, JHJ and Troeberg, L},
title = {Review: Mechanisms of TIMP-3 accumulation and pathogenesis in Sorsby fundus dystrophy.},
journal = {Molecular vision},
volume = {30},
number = {},
pages = {74-91},
pmid = {38601018},
issn = {1090-0535},
mesh = {Humans ; *Macular Degeneration/metabolism/pathology ; Mutation/genetics ; Retina/metabolism ; *Tissue Inhibitor of Metalloproteinase-3/genetics/metabolism ; },
abstract = {Sorsby fundus dystrophy (SFD) is a rare, inherited form of macular degeneration caused by mutations in the gene encoding tissue inhibitor of metalloproteinases 3 (TIMP-3). There are 21 mutations currently associated with SFD, with some variants (e.g., Ser179Cys, Tyr191Cys, and Ser204Cys) having been studied much more than others. We review what is currently known about the identified SFD variants in terms of their dimerization, metalloproteinase inhibition, and impact on angiogenesis, with a focus on disparities between reports and areas requiring further study. We also explore the potential molecular mechanisms leading to the accumulation of extracellular TIMP-3 in SFD and consider how accumulated TIMP-3 causes macular damage. Recent reports have identified extraocular pathologies in a small number of SFD patients. We discuss these intriguing findings and consider the apparent discrepancy between the widespread expression of TIMP-3 and the primarily retinal manifestations of SFD. The potential benefits of novel experimental approaches (e.g., metabolomics and stem cell models) in terms of investigating SFD pathology are presented. The review thus highlights gaps in our current molecular understanding of SFD and suggests ways to support the development of novel therapies.},
}
@article {pmid38599379,
year = {2024},
author = {Mahmoudi, A and Lindenberg, S and Corradetti, G and Emamverdi, M and Oncel, D and Oncel, D and Baek, J and Farahani, A and Almidani, L and He, Y and Abbasgholizadeh, R and Saju, SM and Lee, WK and Wykoff, CC and Sarraf, D and Freund, KB and Sadda, SR},
title = {Predictive Factors Influencing the Evolution of Acquired Vitelliform Lesions in Intermediate Age-Related Macular Degeneration Eyes.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {9},
pages = {863-871},
doi = {10.1016/j.oret.2024.04.003},
pmid = {38599379},
issn = {2468-6530},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; *Disease Progression ; Follow-Up Studies ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; *Visual Acuity ; Risk Factors ; *Fundus Oculi ; Vitelliform Macular Dystrophy/diagnosis ; Aged, 80 and over ; Middle Aged ; Prognosis ; },
abstract = {PURPOSE: In this study, we identify risk factors that predict the progression of acquired vitelliform lesions (AVLs) over time.<br><br>DESIGN: Retrospective cohort study.<br><br>SUBJECTS: One hundred sixty-three eyes of 132 patients with a diagnosis of intermediate age-related macular degeneration (iAMD) with AVL.<br><br>METHODS: This retrospective study evaluated consecutive eyes with AMD from a retina clinic population and included 1181 patients and 2362 eyes. After excluding cases with associated geographic atrophy, macular neovascularization (MNV), vitreomacular traction, and those with <2 years of follow-up data, the final analysis cohort consisted of 163 eyes (132 patients) with &#x2265;1 AVL. The first available visit in which an AVL was evident was considered the baseline visit, and follow-up data were collected from a visit 2 years (&#xb1; 3 months) later. Progression outcomes at the follow-up visit were classified into 6 categories: resorbed, collapsed, MNV, stable, increasing, and decreasing. Subsequently, we analyzed the baseline characteristics for each category and calculated odds ratios (ORs) to predict these various outcomes.<br><br>MAIN OUTCOME MEASURES: The study focused on identifying predictive factors influencing the evolution of AVL in iAMD eyes.<br><br>RESULTS: In total, 163 eyes with AVL had follow-up data at 2 years. The collapsed group demonstrated a significantly greater baseline AVL height and width compared with other groups (P < 0.001). With regard to qualitative parameters, subretinal drusenoid deposits (SDDs) and intraretinal hyperreflective foci (IHRF) at the eye level, AVL located over drusen, and IHRF and external limiting membrane disruption over AVL were significantly more prevalent in the collapsed group compared with other groups (P < 0.05 for all comparisons). Odds ratios for progressing to atrophy after 2 years of follow-up, compared with the resorbed group, were significant for SDD (OR, 2.82; P&#xa0;= 0.048) and AVL height (OR, 1.016; P&#xa0;= 0.006).<br><br>CONCLUSIONS: The presence of SDDs and greater AVL height significantly increases the risk of developing atrophy at the location of AVL after 2 years of follow-up. These findings may be of value in risk prognostication and defining patient populations for inclusion in future early intervention trials aimed at preventing progression to atrophy.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38599207,
year = {2024},
author = {Berlin, A and Fischer, NA and Clark, ME and Kar, D and Swain, TA and Martindale, RM and McGwin, G and Crosson, JN and Sloan, KR and Owsley, C and Curcio, CA},
title = {Quantitative Autofluorescence at AMD's Beginnings Highlights Retinal Topography and Grading System Differences: ALSTAR2 Baseline.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1-13},
pmid = {38599207},
issn = {1423-0267},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY006109/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
abstract = {INTRODUCTION: The aims of the study were to describe baseline quantitative (short-wavelength) autofluorescence (qAF) findings in a large pseudophakic cohort at age-related macular degeneration (AMD)'s beginnings and to assess qAF8 as an outcome measure and evaluate Age-Related Eye Disease Study (AREDS) and Beckman grading systems.<br><br>METHODS: In the ALSTAR2 baseline cohort (NCT04112667), 346 pseudophakic eyes of 188 persons (74.0 &#xb1; 5.5 years) were classified as normal (N = 160 by AREDS, 158 by Beckman), early AMD (eAMD) (N = 104, 66), and intermediate AMD (iAMD) (N = 82, 122). Groups were compared via mean qAF intensities in a 6&#xb0;-8&#xb0; annulus (qAF8) and maps of differences between observations and the overall mean, divided by standard deviation (Z-score).<br><br>RESULTS: qAF8 did not differ significantly among diagnostic groups by either stratification (p = 0.0869 AREDS; p = 0.0569 by Beckman). Notably, 45 eyes considered eAMD by AREDS became iAMD by Beckman. For AREDS-stratified eyes, Z-score maps showed higher centrally located qAF for normal, near the mean in eAMD, and lower values for iAMD. Maps deviated from this pattern for Beckman-stratified eyes.<br><br>CONCLUSIONS: In a large sample of pseudophakic eyes, qAF8 does not differ overall from normal aging to iAMD but also does not capture the earliest AMD activity in the macula lutea. AREDS classification gives results more consistent with a slow decline in histologic autofluorescence than Beckman classification.},
}
@article {pmid38598664,
year = {2024},
author = {Heloterä, H and Siintamo, L and Kivinen, N and Abrahamsson, N and Aaltonen, V and Kaarniranta, K},
title = {Analysis of prognostic and predictive factors in neovascular age-related macular degeneration Kuopio cohort.},
journal = {Acta ophthalmologica},
volume = {102},
number = {6},
pages = {703-713},
doi = {10.1111/aos.16681},
pmid = {38598664},
issn = {1755-3768},
support = {//Sigrid Juselius Foundation/ ; //Finnish Eye Foundation and the Finnish Cultural Foundation/ ; 5503770//Kuopion Yliopistollinen Sairaala/ ; 296840//Academy of Finland/ ; 333302//Academy of Finland/ ; 722717//P&#xe4;ivikki ja Sakari Sohlbergin S&#xe4;&#xe4;ti&#xf6;/ ; //It&#xe4;-Suomen Yliopisto/ ; },
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Aged ; *Intravitreal Injections ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Prognosis ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Tomography, Optical Coherence/methods ; Follow-Up Studies ; Aged, 80 and over ; Fluorescein Angiography/methods ; Finland/epidemiology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Disease Progression ; Fundus Oculi ; Middle Aged ; },
abstract = {PURPOSE: The aim of the study was to explore factors affecting the progression of neovascular age-related macular degeneration (nAMD) and identify predictive factors that can estimate the duration of intravitreal treatments.<br><br>METHODS: This retrospective real-world study included 421 nAMD patients treated at the Kuopio University Hospital during years 2007-2021. The collected data included background demographics, treatment history, visual acuity and retinal biomarker analysis. Impact of baseline factors on age at diagnosis, treatment duration, received treatment intensity and visual acuity gains were analysed.<br><br>RESULTS: Heavy smoking and high body mass index (BMI) were associated with an earlier onset, while the use of anticoagulation and anti-aggregation medication were associated with a later onset of nAMD. A low number of injections during the first year of treatment and the presence of intraretinal fluid (IRF) at baseline were associated with shorter treatment duration. Interestingly, when IRF only patients were compared to subretinal fluid (SRF) only patients, IRF patients showed higher occurrences of subretinal drusenoid deposits (43.5% vs. 15%, p&#x2009;=&#x2009;0.04). In addition, when all patients with IRF were compared to SRF only patients, more hyperreflective foci (HRF) and complete RPE and outer retinal atrophy (cRORA; 20.7% vs. 5%, p&#x2009;=&#x2009;0.02) were observed in patients with IRF.<br><br>CONCLUSIONS: Our results reveal that heavy smoking and high BMI are accelerating factors for earlier emergence of nAMD, while the presence of IRF results in a fast-progressing disease. More intriguingly, the link between IRF and appearance of subretinal drusenoid deposits, HRF, and increased retinal atrophy was observed.},
}
@article {pmid38595281,
year = {2024},
author = {Molins, B and Rodríguez, A and Llorenç, V and Adán, A},
title = {Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration.},
journal = {Neural regeneration research},
volume = {19},
number = {12},
pages = {2626-2636},
pmid = {38595281},
issn = {1673-5374},
abstract = {Age-related macular degeneration, a multifactorial inflammatory degenerative retinal disease, ranks as the leading cause of blindness in the elderly. Strikingly, there is a scarcity of curative therapies, especially for the atrophic advanced form of age-related macular degeneration, likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier, the prime target tissue of age-related macular degeneration. Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier, integrated by the dynamic interaction of the retinal pigment epithelium, the Bruch's membrane, and the underlying choriocapillaris. The Bruch's membrane provides structural and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier, and therefore adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrier. In the last years, advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials. This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healthy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems. Then, we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling, discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.},
}
@article {pmid38595182,
year = {2024},
author = {Majumdar, D and Webb, D and Parsons, S and Selwan-Lewis, EM and Rettig, T and Chastain, E and Obanor, W and Birnberg, R and Kuang, A},
title = {Understanding preferences for receiving health communications and information about clinical trials: a cross-sectional study among US adults.},
journal = {Current medical research and opinion},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/03007995.2024.2340720},
pmid = {38595182},
issn = {1473-4877},
abstract = {OBJECTIVE: Effective health communication is critical for understanding and acting on health information. This cross-sectional study explored participants' understanding of their health condition, their preferences for receiving health communications, and their interest in receiving clinical trial results across several therapeutic areas.<br><br>METHODS: The study recruited participants via social media, email newsletters, and advocacy organizations. An online screener captured demographic information (health conditions, age, race/ethnicity, gender, and education). Eligible participants were emailed an online survey assessing preferred sources and formats for receiving health information, interest in learning about topics related to the results of clinical trials, and health literacy levels.<br><br>RESULTS: In total, 449 participants (median age, 35&#x2009;years [range, 18-76]; White, 53%; higher education, 65%; mean (range) health literacy score, 1.9 [0.4-3.0]) from 45&#x2009;US states completed the survey representing 12 disease indications (bipolar, blood and solid tumor cancers, irritable bowel syndrome, inflammatory bowel disease, major depressive disorder, migraine, Parkinson's, psoriasis/atopic dermatitis, retinal vein occlusion/macular degeneration, rheumatoid arthritis, and spasticity). Healthcare providers were the preferred source of health information (59%), followed by Internet searches (11%). Least preferred sources were social media (5%), friends/family (3%), and email newsletters (2%). Participants preferred multiple formats and ranked reading materials online as most preferred (33%), along with videos (28%) and infographics (27%). Printed materials (14%) and audio podcasts (9%) were the least preferred formats. A majority of the participants reported that the health information they found was hard to understand (57%) and confusing (62%). Most participants (85%) were somewhat/very interested in learning about clinical trial results, with the highest interest in short summaries of safety (78%) and efficacy (74%) results.<br><br>CONCLUSION: Effective health communication may be achieved via multiple formats shared directly by healthcare providers.},
}
@article {pmid38594962,
year = {2024},
author = {Wu, Q and Zhu, J and Zhang, X and Xu, X and Luo, D and Lin, Y and Yan, M and Song, Y},
title = {The antioxidant effect of tetrahedral framework nucleic acid-based delivery of small activating RNA targeting DJ-1 on retinal oxidative stress injury.},
journal = {Cell proliferation},
volume = {57},
number = {8},
pages = {e13635},
pmid = {38594962},
issn = {1365-2184},
support = {2202YFC2502800//National Key Research and Development Program of China/ ; 2022020801020520//Intellectual Innovation Project of Wuhan/ ; 20210517KY04//Postdoctoral Foundation of General Hospital of Central Theater Command/ ; 20211227KY21//Postdoctoral Foundation of General Hospital of Central Theater Command/ ; },
mesh = {Humans ; *Oxidative Stress/drug effects ; *Protein Deglycase DJ-1/metabolism/genetics ; *Antioxidants/pharmacology/chemistry ; *Human Umbilical Vein Endothelial Cells ; Retinal Pigment Epithelium/metabolism/drug effects ; Apoptosis/drug effects ; Reactive Oxygen Species/metabolism ; NF-E2-Related Factor 2/metabolism ; Cell Survival/drug effects ; Retina/metabolism/drug effects ; Nucleic Acids/pharmacology/metabolism ; Cell Line ; },
abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the world's leading causes of blindness. The retinal pigment epithelium (RPE) and vascular endothelial cell exposed to oxidative stress is the major cause of AMD and DR. DJ-1, an important endogenous antioxidant, its overexpression is considered as a promising antioxidant treatment for AMD and DR. Here, we modified the tetrahedral frame nucleic acids (tFNAs) with DJ-1 saRNAs as a delivery system, and synthesized a novel nanocomplex (tFNAs-DJ-1 saRNAs). In vitro studies show that tFNAs-DJ-1 saRNAs can efficiently transfer DJ-1 saRNAs to human umbilical vein endothelial cells (HUVECs) and ARPE-19s, and significantly increased their cellular DJ-1 level. Reactive oxygen species expression in H2O2-treated HUVECs and ARPE-19s were decreased, cell viability was enhanced and cell apoptosis were inhibited when tFNAs-DJ-1 saRNAs were delivered. Moreover, tFNAs-DJ-1 saRNAs preserved mitochondrial structure and function under oxidative stress conditions. In the aspect of molecular mechanism, tFNAs-DJ-1 saRNAs activated Erk and Nrf2 pathway, which might contribute to its protective effects against oxidative stress damage. To conclude, this study shows the successfully establishment of a simple but effective delivery system of DJ-1 saRNAs associated with antioxidant effects in AMD and DR, which may be a promising agent for future treatment in oxidative stress-related retinal disorders.},
}
@article {pmid38593971,
year = {2024},
author = {Zhang, Z and Liang, F and Chang, J and Shan, X and Yin, Z and Wang, L and Li, S},
title = {Autophagy in dry AMD: A promising therapeutic strategy for retinal pigment epithelial cell damage.},
journal = {Experimental eye research},
volume = {242},
number = {},
pages = {109889},
doi = {10.1016/j.exer.2024.109889},
pmid = {38593971},
issn = {1096-0007},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Autophagy/physiology ; *Oxidative Stress/physiology ; Inflammasomes/metabolism ; Lipofuscin/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Geographic Atrophy/metabolism/pathology ; },
abstract = {Dry age-related macular degeneration (AMD) is a prevalent clinical condition that leads to permanent damage to central vision and poses a significant threat to patients' visual health. Although the pathogenesis of dry AMD remains unclear, there is consensus on the role of retinal pigment epithelium (RPE) damage. Oxidative stress and chronic inflammation are major contributors to RPE cell damage, and the NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) inflammasome mediates the inflammatory response leading to apoptosis in RPE cells. Furthermore, lipofuscin accumulation results in oxidative stress, NLRP3 activation, and the development of vitelliform lesions, a hallmark of dry AMD, all of which may contribute to RPE dysfunction. The process of autophagy, involving the encapsulation, recognition, and transport of accumulated proteins and dead cells to the lysosome for degradation, is recognized as a significant pathway for cellular self-protection and homeostasis maintenance. Recently, RPE cell autophagy has been discovered to be closely linked to the development of macular degeneration, positioning autophagy as a cutting-edge research area in the realm of dry AMD. In this review, we present an overview of how lipofuscin, oxidative stress, and the NLRP3 inflammasome damage the RPE through their respective causal mechanisms. We summarized the connection between autophagy, oxidative stress, and NLRP3 inflammatory cytokines. Our findings suggest that targeting autophagy improves RPE function and sustains visual health, offering new perspectives for understanding the pathogenesis and clinical management of dry AMD.},
}
@article {pmid38593635,
year = {2024},
author = {Zhang, Z and Gu, Q and Chen, L and Yuan, D and Gu, X and Qian, H and Xie, P and Liu, Q and Hu, Z},
title = {Selective microRNA expression of exosomes from retinal pigment epithelial cells by oxidative stress.},
journal = {Vision research},
volume = {220},
number = {},
pages = {108388},
doi = {10.1016/j.visres.2024.108388},
pmid = {38593635},
issn = {1878-5646},
mesh = {*Exosomes/metabolism ; *MicroRNAs/metabolism ; *Retinal Pigment Epithelium/metabolism ; *Oxidative Stress/physiology ; Animals ; Mice ; Mice, Inbred C57BL ; Apoptosis ; Gene Expression Regulation/physiology ; Humans ; Reactive Oxygen Species/metabolism ; },
abstract = {The function of exosomal miRNAs (miRs) in retinal degeneration is largely unclear. We were aimed to investigate the functions of exosomes as well as their miRs derived from retinal pigment epithelial (RPE) cells following exposure to oxidative stress (OS). After the OS by lipopolysaccharide and rotenone on RPE cells, interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) were upregulated, along with the decreased mitochondrial membrane potential and upregulated oxidative damage marker 8-OH-dG in RPE cells. RPE-derived exosomes were then isolated, identified, injected into the subretinal space in mice. After subretinal injection, RPE-exosomes after OS not only induced higher ROS level and apoptotic retinal cells, but also elevated IL-1β, IL-6 alongside TNF-α expressions among retina/RPE/choroidal complex. Next, miRs inside the exosomes were sequenced by the next generation sequencing (NGS) technology. NGS revealed that certain miRs were abundant in exosomes, while others were selectively kept by RPE cells. Further, downregulated miRs, like miR-125b-5p, miR-125a-5p, alongside miR-128-3p, and upregulated miR, such as miR-7-5p were validated byRT-qPCR. Finally, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to find the possible target genes of those selective exosomal miRs. Our results proved that the RPE-derived exosomes after OS selectively express certain miRs, providing novel insights into the pathogenesis of age-related macular degeneration (AMD) in future.},
}
@article {pmid38592228,
year = {2024},
author = {Hirai, H and Yamashita, M and Ijuin, N and Jimura, H and Nishi, T and Ogata, N and Ueda, T},
title = {Evaluation of Choroidal Structure in Type 1 Macular Neovascularization Using Different Optical Coherence Tomography Analyses: Scale Bar and Binarization.},
journal = {Journal of clinical medicine},
volume = {13},
number = {5},
pages = {},
pmid = {38592228},
issn = {2077-0383},
abstract = {BACKGROUND: Macular neovascularization (MNV) has been evaluated by optical coherence tomography (OCT) imaging using various approaches. However, few studies have examined their differences. This study analyzed type 1 MNV with a combination of two approaches: scale bar and binarization.<br><br>METHODS: We enrolled 84 patients with untreated type 1 MNV. We measured choroidal parameters using a scale bar and defined the ratios of superficial choroidal thickness to choroidal vessel diameter (SV ratios). We also used binarization and calculated the ratios of the luminal to the choroidal area (LC ratios) in two directions (horizontal and vertical).<br><br>RESULTS: Fifty-one patients (61%) were classified as having polyps. SV ratios in the group with polyps were significantly lower than in the group without (p < 0.001). The receiver operating characteristic (ROC) curve showed that the SV ratio was predictive of polyps (AUC 0.733, 95% CI: 0.621-0.844). In patients without polyps, horizontal LC ratios were significantly higher in a subgroup with subretinal fluid than in those without (p = 0.047). The ROC curve showed that the LC ratio was predictive of subretinal fluid (AUC 0.722, 95% CI: 0.517-0.926).<br><br>CONCLUSION: The SV ratio reflects the MNV disease type, whereas the LC ratio reflects MNV disease activity. Establishing cut-off values for each ratio may be useful for MNV diagnosis.},
}
@article {pmid38591046,
year = {2024},
author = {Mai, J and Lachinov, D and Reiter, GS and Riedl, S and Grechenig, C and Bogunovic, H and Schmidt-Erfurth, U},
title = {Deep Learning-Based Prediction of Individual Geographic Atrophy Progression from a Single Baseline OCT.},
journal = {Ophthalmology science},
volume = {4},
number = {4},
pages = {100466},
pmid = {38591046},
issn = {2666-9145},
abstract = {OBJECTIVE: To identify the individual progression of geographic atrophy (GA) lesions from baseline OCT images of patients in routine clinical care.<br><br>DESIGN: Clinical evaluation of a deep learning-based algorithm.<br><br>SUBJECTS: One hundred eighty-four eyes of 100 consecutively enrolled patients.<br><br>METHODS: OCT and fundus autofluorescence (FAF) images (both Spectralis, Heidelberg Engineering) of patients with GA secondary to age-related macular degeneration in routine clinical care were used for model validation. Fundus autofluorescence images were annotated manually by delineating the GA area by certified readers of the Vienna Reading Center. The annotated FAF images were anatomically registered in an automated manner to the corresponding OCT scans, resulting in 2-dimensional en face OCT annotations, which were taken as a reference for the model performance. A deep learning-based method for modeling the GA lesion growth over time from a single baseline OCT was evaluated. In addition, the ability of the algorithm to identify fast progressors for the top 10%, 15%, and 20% of GA growth rates was analyzed.<br><br>MAIN OUTCOME MEASURES: Dice similarity coefficient (DSC) and mean absolute error (MAE) between manual and predicted GA growth.<br><br>RESULTS: The deep learning-based tool was able to reliably identify disease activity in GA using a standard OCT image taken at a single baseline time point. The mean DSC for the total GA region increased for the first 2 years of prediction (0.80-0.82). With increasing time intervals beyond 3 years, the DSC decreased slightly to a mean of 0.70. The MAE was low over the first year and with advancing time slowly increased, with mean values ranging from 0.25 mm to 0.69 mm for the total GA region prediction. The model achieved an area under the curve of 0.81, 0.79, and 0.77 for the identification of the top 10%, 15%, and 20% growth rates, respectively.<br><br>CONCLUSIONS: The proposed algorithm is capable of fully automated GA lesion growth prediction from a single baseline OCT in a time-continuous fashion in the form of en face maps. The results are a promising step toward clinical decision support tools for therapeutic dosing and guidance of patient management because the first treatment for GA has recently become available.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38590577,
year = {2024},
author = {Li, J and Yang, Z and Li, X and Li, D and Yang, J and Dang, M},
title = {Comparative quantitative analysis of optical coherence tomography angiography in varied morphologies of macular neovascularization following intravitreal conbercept and ranibizumab treatments for neovascular age‑related macular degeneration.},
journal = {Experimental and therapeutic medicine},
volume = {27},
number = {5},
pages = {214},
pmid = {38590577},
issn = {1792-1015},
abstract = {The present study aimed to examine the optical coherence tomography angiography (OCTA) parameters associated with macular neovascularization (MNV) in patients diagnosed with neovascular age-related macular degeneration (nAMD) and treated with either intravitreal conbercept (IVC) or ranibizumab (IVR). It enrolled 39 nAMD patients presenting with MNV, including 23 in the IVC group and 16 in the IVR group. All participants were treatment-naïve with intravitreal therapy and they underwent treatment following a '3+PRN' regimen. The MNV patterns identified through OCTA were categorized as Medusa, tangled, seafan and other variations. Key outcome measures encompassed best-corrected visual acuity (BCVA), MNV vascular area (MNV-VA), MNV vascular density (MNV-VD) ratio and central macular thickness (CMT). In the present study, 44 eyes were included, with 28 eyes undergoing treatment with IVC and 18 eyes with IVR. On day 90, there was a statistically significant improvement in mean BCVA from baseline among all patients treated with IVC (P=0.002). Notably, improved outcomes were observed in those with the 'tangled' pattern compared with the other three patterns (P=0.007). CMT exhibited a significant decrease from baseline (P=0.007), with consistent improvement observed across all four patterns (P=0.052) on day 90. The mean MNV-VA decreased in all patients, reaching statistical significance for the Medusa pattern (P=0.008), although the improvement in visual acuity was deemed unsatisfactory. Patients with the seafan pattern treated with IVR improved significantly in BCVA (P=0.042). The mean CMT significantly improved from baseline (P=0.001), consistent across the four patterns (P=0.114). Significant improvements were noted in the mean MNV-VA for the seafan pattern and in the mean MNV-VD ratio for the other patterns. The two regimens had no significant differences regarding BCVA, CMT, and MNV parameters. Conbercept emerged as a viable treatment option for patients presenting with tangled MNV patterns. On the other hand, ranibizumab might be considered an effective intervention for individuals with seafan MNV patterns. Notably, the Medusa MNV pattern was associated with a morphologic configuration indicative of a poor prognosis.},
}
@article {pmid38589964,
year = {2024},
author = {Funatsu, R and Terasaki, H and Mihara, N and Sonoda, S and Shiihara, H and Sakamoto, T},
title = {Evaluating photodynamic therapy versus brolucizumab as a second-line treatment for polypoidal choroidal vasculopathy.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {32},
pmid = {38589964},
issn = {2056-9920},
support = {21H03095//Japan Society for the Promotion of Science London/ ; },
abstract = {BACKGROUND: To compare the one-year outcomes between intravitreal brolucizumab (IVBr) monotherapy and photodynamic therapy (PDT) as a second-line treatment in patients with polypoidal choroidal vasculopathy (PCV) who did not respond to first-line therapy.<br><br>METHODS: This case-control study included eyes with PCV that do not respond to aflibercept or ranibizumab. The patients were retrospectively registered. We compared outcomes, including best-corrected visual acuity (BCVA), anatomical results, and the need for additional treatments, between IVBr and a combination therapy using PDT as second-line treatments for refractory PCV, after adjusting for potential confounders. We analyzed E-values to evaluate the robustness of the results against unmeasured confounders.<br><br>RESULTS: Twenty-two eyes received IVBr, and twenty-four underwent PDT. No apparent differences were observed in BCVA and central macular thickness (CMT) changes from baseline between the groups (IVBr vs. PDT: BCVA, 0.01&#x2009;&#xb1;&#x2009;0.47 logMAR vs. 0.04&#x2009;&#xb1;&#x2009;0.18 logMAR, P-value&#x2009;=&#x2009;0.756; CMT: -&#xa0;36.3&#x2009;&#xb1;&#x2009;99.4&#xa0;&#x3bc;m vs. -&#xa0;114.7&#x2009;&#xb1;&#x2009;181.4&#xa0;&#x3bc;m, P-value&#x2009;=&#x2009;0.146). Only in the PDT group, five eyes (20.8%) did not require additional treatment after the second-line treatment, the adjusted odds ratio indicating no further treatment needed was 11.98 (95% confidence interval: 1.42-2070.07, P-value&#x2009;=&#x2009;0.019). The E-value for the adjusted odds ratio was 23.44.<br><br>CONCLUSIONS: Both second-line treatments for PCV exhibited similar visual and anatomical outcomes. Only in the PDT-treated eyes were there some patients who did not require further treatment after second-line therapy.},
}
@article {pmid38589936,
year = {2024},
author = {Mares, V and Nehemy, MB and Bogunovic, H and Frank, S and Reiter, GS and Schmidt-Erfurth, U},
title = {AI-based support for optical coherence tomography in age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {31},
pmid = {38589936},
issn = {2056-9920},
abstract = {Artificial intelligence (AI) has emerged as a transformative technology across various fields, and its applications in the medical domain, particularly in ophthalmology, has gained significant attention. The vast amount of high-resolution image data, such as optical coherence tomography (OCT) images, has been a driving force behind AI growth in this field. Age-related macular degeneration (AMD) is one of the leading causes for blindness in the world, affecting approximately 196 million people worldwide in 2020. Multimodal imaging has been for a long time the gold standard for diagnosing patients with AMD, however, currently treatment and follow-up in routine disease management are mainly driven by OCT imaging. AI-based algorithms have by their precision, reproducibility and speed, the potential to reliably quantify biomarkers, predict disease progression and assist treatment decisions in clinical routine as well as academic studies. This review paper aims to provide a summary of the current state of AI in AMD, focusing on its applications, challenges, and prospects.},
}
@article {pmid38589459,
year = {2024},
author = {Niño-Joya, AF and Martínez-Blanco, AM and Salamanca, O and Bonilla-Escobar, FJ},
title = {Comment on: "Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen".},
journal = {Eye (London, England)},
volume = {38},
number = {13},
pages = {2661},
pmid = {38589459},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; *Disease Progression ; Ranibizumab/therapeutic use/administration &amp; dosage ; Wet Macular Degeneration/drug therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; Intravitreal Injections ; Choroidal Neovascularization/drug therapy ; },
}
@article {pmid38586868,
year = {2024},
author = {Niu, Y and Ji, J and Yao, K and Fu, Q},
title = {Regenerative treatment of ophthalmic diseases with stem cells: Principles, progress, and challenges.},
journal = {Advances in ophthalmology practice and research},
volume = {4},
number = {2},
pages = {52-64},
pmid = {38586868},
issn = {2667-3762},
abstract = {BACKGROUND: Degenerate eye disorders, such as glaucoma, cataracts and age-related macular degeneration (AMD), are prevalent causes of blindness and visual impairment worldwide. Other eye disorders, including limbal stem cell deficiency (LSCD), dry eye diseases (DED), and retinitis pigmentosa (RP), result in symptoms such as ocular discomfort and impaired visual function, significantly impacting quality of life. Traditional therapies are limited, primarily focus on delaying disease progression, while emerging stem cell therapy directly targets ocular tissues, aiming to restore ocular function by reconstructing ocular tissue.<br><br>MAIN TEXT: The utilization of stem cells for the treatment of diverse degenerative ocular diseases is becoming increasingly significant, owing to the regenerative and malleable properties of stem cells and their functional cells. Currently, stem cell therapy for ophthalmopathy involves various cell types, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells (RPCs). In the current article, we will review the current progress regarding the utilization of stem cells for the regeneration of ocular tissue covering key eye tissues from the cornea to the retina. These therapies aim to address the loss of functional cells, restore damaged ocular tissue and or in a paracrine-mediated manner. We also provide an overview of the ocular disorders that stem cell therapy is targeting, as well as the difficulties and opportunities in this field.<br><br>CONCLUSIONS: Stem cells can not only promote tissue regeneration but also release exosomes to mitigate inflammation and provide neuroprotection, making stem cell therapy emerge as a promising approach for treating a wide range of eye disorders through multiple mechanisms.},
}
@article {pmid38585147,
year = {2024},
author = {Zhang, Q and Jiang, Y and Deng, C and Wang, J},
title = {Effects and potential mechanisms of exercise and physical activity on eye health and ocular diseases.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1353624},
pmid = {38585147},
issn = {2296-858X},
abstract = {In the field of eye health, the profound impact of exercise and physical activity on various ocular diseases has become a focal point of attention. This review summarizes and elucidates the positive effects of exercise and physical activities on common ocular diseases, including dry eye disease (DED), cataracts, myopia, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD). It also catalogues and offers exercise recommendations based on the varying impacts that different types and intensities of physical activities may have on specific eye conditions. Beyond correlations, this review also compiles potential mechanisms through which exercise and physical activity beneficially affect eye health. From mitigating ocular oxidative stress and inflammatory responses, reducing intraocular pressure, enhancing mitochondrial function, to promoting ocular blood circulation and the release of protective factors, the complex biological effects triggered by exercise and physical activities reveal their substantial potential in preventing and even assisting in the treatment of ocular diseases. This review aims not only to foster awareness and appreciation for how exercise and physical activity can improve eye health but also to serve as a catalyst for further exploration into the specific mechanisms and key targets through which exercise impacts ocular health. Such inquiries are crucial for advancing innovative strategies for the treatment of eye diseases, thereby holding significant implications for the development of new therapeutic approaches.},
}
@article {pmid38584442,
year = {2024},
author = {Lee, Y and Kim, JS},
title = {Visual Outcome of Nontraumatic Dense Vitreous Hemorrhage in Patients without Diabetes: A Single-Center Case Series.},
journal = {Korean journal of ophthalmology : KJO},
volume = {38},
number = {3},
pages = {179-184},
pmid = {38584442},
issn = {2092-9382},
mesh = {Humans ; *Vitreous Hemorrhage/diagnosis/etiology/physiopathology/surgery ; Retrospective Studies ; Male ; *Visual Acuity/physiology ; Female ; Middle Aged ; Aged ; *Vitrectomy/methods ; Adult ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: Dense vitreous hemorrhage is a vision-threatening disease with varied clinical manifestations. Herein, we aimed to evaluate its causes and outcomes in patients without diabetes.<br><br>METHODS: A retrospective cohort including 60 eyes from 60 patients with an initial diagnosis of nontraumatic fundus-obscuring dense vitreous hemorrhages and without diabetes was recruited. The relevant medical records from January 2013 to December 2019 were reviewed and analyzed. We classified patients into the following four groups, depending on the underlying cause of dense vitreous hemorrhage: eight cases in the age-related macular degeneration group, four cases in the posterior vitreous detachment group, 20 cases in the tear group, and 28 cases in the vascular group.<br><br>RESULTS: The most common cause of dense vitreous hemorrhage was retinal vascular obstructive disease (46.7%); the age-related macular degeneration group showed the worst prognosis. The extent of best-corrected visual acuity change was significantly better in patients who underwent vitrectomy compared to those receiving conservative treatment; best-corrected visual acuity change (logarithm of the minimum angle of resolution) was 1.62 &#xb1; 0.57 in the surgical group and 1.06 &#xb1; 0.88 in the nonsurgical group (Student t-test, p = 0.007).<br><br>CONCLUSIONS: Retinal vascular disease is the most common cause of vitreous hemorrhages, and surgical treatments have a better visual outcome than nonsurgical treatments.},
}
@article {pmid38582458,
year = {2024},
author = {Cen, H and Sun, M and Zheng, B and Peng, W and Wen, Q and Lin, Z and Zhang, X and Zhou, N and Zhu, G and Yu, X and Zhang, L and Liang, L},
title = {Hyaluronic acid modified nanocarriers for aerosolized delivery of verteporfin in the treatment of acute lung injury.},
journal = {International journal of biological macromolecules},
volume = {267},
number = {Pt 1},
pages = {131386},
doi = {10.1016/j.ijbiomac.2024.131386},
pmid = {38582458},
issn = {1879-0003},
mesh = {*Acute Lung Injury/drug therapy ; *Hyaluronic Acid/chemistry ; Animals ; Mice ; *Verteporfin/administration &amp; dosage/pharmacology/therapeutic use ; *Nanoparticles/chemistry ; *Drug Carriers/chemistry ; RAW 264.7 Cells ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; Aerosols ; Male ; Drug Delivery Systems ; Administration, Inhalation ; },
abstract = {Verteporfin (VER), a photosensitizer used in macular degeneration therapy, has shown promise in controlling macrophage polarization and alleviating inflammation in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). However, its hydrophobicity, limited bioavailability, and side effects hinder its therapeutic potential. In this study, we aimed to enhance the therapeutic potential of VER through pulmonary nebulized drug delivery for ALI/ARDS treatment. We combined hydrophilic hyaluronic acid (HA) with an oil-in-water system containing a poly(lactic acid-co-glycolic acid) (PLGA) copolymer of VER to synthesize HA@PLGA-VER (PHV) nanoparticles with favorable surface characteristics to improve the bioavailability and targeting ability of VER. PHV possesses suitable electrical properties, a narrow size distribution (approximately 200 nm), and favorable stability. In vitro and in vivo studies demonstrated the excellent biocompatibility, safety, and anti-inflammatory responses of the PHV by suppressing M1 macrophage polarization while inducing M2 polarization. The in vivo experiments indicated that the treatment with aerosolized nano-VER (PHV) allowed more drugs to accumulate and penetrate into the lungs, improved the pulmonary function and attenuated lung injury, and mortality of ALI mice, achieving improved therapeutic outcomes. These findings highlight the potential of PHV as a promising delivery system via nebulization for enhancing the therapeutic effects of VER in ALI/ARDS.},
}
@article {pmid38582267,
year = {2024},
author = {Kumar, A and Nagasaka, Y and Jayananthan, V and Zidan, A and Heisler-Taylor, T and Ambati, J and Tamiya, S and Kerur, N},
title = {Therapeutic targeting of telomerase ameliorates experimental choroidal neovascularization.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1870},
number = {5},
pages = {167156},
pmid = {38582267},
issn = {1879-260X},
support = {P30 EY032857/EY/NEI NIH HHS/United States ; R01 AI148740/AI/NIAID NIH HHS/United States ; R01 EY028027/EY/NEI NIH HHS/United States ; R01 AI148741/AI/NIAID NIH HHS/United States ; R21 EY030651/EY/NEI NIH HHS/United States ; R01 EY029799/EY/NEI NIH HHS/United States ; R01 EY031039/EY/NEI NIH HHS/United States ; R01 EY030060/EY/NEI NIH HHS/United States ; R01 EY024068/EY/NEI NIH HHS/United States ; },
mesh = {*Telomerase/antagonists &amp; inhibitors/genetics/metabolism ; Animals ; *Choroidal Neovascularization/pathology/metabolism/drug therapy ; Mice ; *Disease Models, Animal ; Vascular Endothelial Growth Factor A/metabolism/genetics ; Mice, Inbred C57BL ; Aminobenzoates/pharmacology ; RNA/genetics/metabolism ; Oligonucleotides, Antisense/pharmacology ; Naphthalenes ; },
abstract = {Choroidal neovascularization (CNV) is the principal driver of blindness in neovascular age-related macular degeneration (nvAMD). Increased activity of telomerase, has been associated with endothelial cell proliferation, survival, migration, and invasion in the context of tumor angiogenesis. Expanding on this knowledge, we investigated the role of telomerase in the development of CNV in mouse model. We observed increased gene expression and activity of telomerase in mouse CNV. Genetic deficiency of the telomerase components, telomerase reverse transcriptase (Tert) and telomerase RNA component (Terc) suppressed laser-induced CNV in mice. Similarly, a small molecule inhibitor of TERT (BIBR 1532), and antisense oligonucleotides (ASOs) targeting Tert and Terc reduced CNV growth. Bone marrow chimera studies suggested that telomerase activity in non-bone marrow-derived cells is crucial for the development of CNV. Comparison of BIBR 1532 with VEGF neutralizing therapeutic strategy in mouse revealed a comparable level of angiosuppressive activity. However, when BIBR and anti-VEGF antibodies were administered as a combination at sub-therapeutic doses, a statistically significant suppression of CNV was observed. These findings underscore the potential benefits of combining sub-therapeutic doses of BIBR and anti-VEGF antibodies for developing newer therapeutic strategies for NV-AMD. Telomerase inhibition with BIBR 1532 suppressed induction of multiple cytokines and growth factors critical for neovascularization. In conclusion, our study identifies telomerase as a promising therapeutic target for treating neovascular disease of the eye and thus provides a proof of principle for further exploration of telomerase inhibition as a novel treatment strategy for nvAMD.},
}
@article {pmid38582179,
year = {2024},
author = {Sarmento, C and Duarte, ARC and Rita Jesus, A},
title = {Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?.},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V},
volume = {198},
number = {},
pages = {114276},
doi = {10.1016/j.ejpb.2024.114276},
pmid = {38582179},
issn = {1873-3441},
mesh = {Humans ; Eye/metabolism ; *Eye Diseases/drug therapy ; Drug Delivery Systems ; Pharmaceutical Preparations ; *Macular Degeneration/drug therapy ; },
abstract = {The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.},
}
@article {pmid38581435,
year = {2024},
author = {Yen, CY and Chiu, CM and Fang, IM},
title = {MicroRNA expression profiling in tears and blood as predictive biomarkers for anti-VEGF treatment response in wet age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {9},
pages = {2875-2884},
pmid = {38581435},
issn = {1435-702X},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy/diagnosis/genetics/metabolism ; *MicroRNAs/genetics ; Prospective Studies ; Female ; Male ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors/genetics/metabolism ; Aged ; *Biomarkers/metabolism/blood ; *Angiogenesis Inhibitors/therapeutic use ; *Aqueous Humor/metabolism ; *Tears/metabolism ; *Gene Expression Profiling/methods ; *Intravitreal Injections ; Ranibizumab/administration &amp; dosage/therapeutic use ; Visual Acuity ; Tomography, Optical Coherence/methods ; Gene Expression Regulation ; Follow-Up Studies ; Treatment Outcome ; Aged, 80 and over ; },
abstract = {PURPOSE: This study aimed to investigate the potential of microRNAs (miRNAs) in tears, blood, and aqueous humor as biomarkers for predicting treatment response in wet age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy.<br><br>METHODS: In a single-center prospective cohort study, treatment-na&#xef;ve wet AMD patients and age-matched controls were enrolled. Clinical data and miRNA levels (miR-199a-3p, miR-365-3p, miR-200b-3p, miR-195-5p, miR-335-5p, and miR-185-5p) in tears, blood, and aqueous humor were collected. Treatment response was categorized into responders and non-responders based on visual acuity and central subfield thickness. MiRNA levels were quantified using reverse-transcription PCR. Statistical analyses were performed, including ROC analysis, to evaluate predictive accuracy.<br><br>RESULTS: Dysregulated miRNA profiles were observed in wet AMD tears and blood compared to controls. Specifically, miR-199a-3p, miR-195-5p, and miR-185-5p were upregulated, while miR-200b-3p was downregulated in tears. All six miRNAs were elevated in wet AMD blood samples. Notably, responders showed higher tear expression of miR-195-5p and miR-185-5p. Combining these miRNAs yielded the highest predictive power (AUC&#x2009;=&#x2009;0.878, p&#x2009;=&#x2009;0.006) for anti-VEGF responders.<br><br>CONCLUSIONS: Dysregulated miRNA profiles in tears and blood suggest their potential as biomarkers for wet AMD. MiR-195-5p and miR-185-5p in tears demonstrate predictive value for anti-VEGF treatment responders. This study underscores the non-invasive prediction potential of miRNA tear analysis in wet AMD treatment responses.},
}
@article {pmid38581209,
year = {2024},
author = {Ahn, J and Choi, M},
title = {Advancements and turning point of artificial intelligence in ophthalmology: A comprehensive analysis of research trends and collaborative networks.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {44},
number = {5},
pages = {1031-1040},
doi = {10.1111/opo.13315},
pmid = {38581209},
issn = {1475-1313},
support = {2022-0659//Seoul National University of Science and Technology/ ; },
mesh = {*Artificial Intelligence/trends ; Humans ; *Ophthalmology ; Biomedical Research/trends ; Eye Diseases/diagnosis/therapy ; },
abstract = {Artificial intelligence (AI) has emerged as a transformative force with great potential in various fields, including healthcare. In recent years, AI has garnered significant attention due to its potential to revolutionise ophthalmology, leading to advancements in patient care such as disease detection, diagnosis, treatment and monitoring of disease progression. This study presents a comprehensive analysis of the research trends and collaborative networks at the intersection of AI and ophthalmology. In this study, we conducted an extensive search of the Web of Science Core Collection to identify articles related to 'artificial intelligence' in ophthalmology published from 1968 to 2023. We performed co-occurrence keywords and co-authorship network analyses using VOSviewer software to explore the relationships between keywords and country collaboration. We found a remarkable surge in articles applying AI in ophthalmology after 2017, marking a turning point in the integration of AI within the medical field. The primary application of AI shifted towards the diagnosis of ocular disease, which was particularly evident through keywords such as glaucoma, diabetic retinopathy and age-related macular degeneration. Analysis of the collaboration networks of countries revealed a global expansion of ophthalmology-related AI research. This study provides valuable insights into the evolving landscape of AI integration in ophthalmology, indicating its growing potential for enhancing disease detection, diagnosis, treatment planning and monitoring of disease progression. In order to translate AI technologies into clinical practice effectively, it is imperative to comprehend the evolving research trends and advancements at the intersection of AI and ophthalmology.},
}
@article {pmid38581053,
year = {2024},
author = {Llorián-Salvador, M and de la Fuente, AG and McMurran, CE and Dashwood, A and Dooley, J and Liston, A and Penalva, R and Dombrowski, Y and Stitt, AW and Fitzgerald, DC},
title = {Regulatory T cells limit age-associated retinal inflammation and neurodegeneration.},
journal = {Molecular neurodegeneration},
volume = {19},
number = {1},
pages = {32},
pmid = {38581053},
issn = {1750-1326},
support = {/WT_/Wellcome Trust/United Kingdom ; Wellcome ISSF Postdoctoral Fellowship/WT_/Wellcome Trust/United Kingdom ; 110138/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Mice ; Animals ; *T-Lymphocytes, Regulatory ; Gliosis ; Retina ; *Macular Degeneration ; Inflammation ; },
abstract = {BACKGROUND: Ageing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown.<br><br>METHODS: Regulatory T cells were selectively depleted in both young (2-4 months) and aged (18-23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni's post hoc test.<br><br>RESULTS: Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes.<br><br>CONCLUSION: Our findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.},
}
@article {pmid38579938,
year = {2024},
author = {Dieguez, HH and Romeo, HE and Alaimo, A and Bernal Aguirre, NA and Calanni, JS and Adán Aréan, JS and Alvarez, S and Sciurano, R and Rosenstein, RE and Dorfman, D},
title = {Mitochondrial quality control in non-exudative age-related macular degeneration: From molecular mechanisms to structural and functional recovery.},
journal = {Free radical biology &amp; medicine},
volume = {219},
number = {},
pages = {17-30},
doi = {10.1016/j.freeradbiomed.2024.03.024},
pmid = {38579938},
issn = {1873-4596},
mesh = {Animals ; *Mitochondria/metabolism/pathology ; Mice ; *Macular Degeneration/pathology/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *AMP-Activated Protein Kinases/metabolism ; *Mitochondrial Dynamics ; Humans ; *Mice, Inbred C57BL ; *Disease Models, Animal ; Metformin/pharmacology ; },
abstract = {Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynamics (biogenesis, fusion, fission, and mitophagy), which is under the central control of AMP-activated kinase (AMPK), in turn, determines mitochondrial quality. We have developed a NE-AMD model in C57BL/6J mice induced by unilateral superior cervical ganglionectomy (SCGx), which progressively reproduces the disease hallmarks circumscribed to the temporal region of the RPE/outer retina that exhibits several characteristics of the human macula. In this work we have studied RPE mitochondrial structure, dynamics, function, and AMPK role on these parameters' regulation at the nasal and temporal RPE from control eyes and at an early stage of experimental NE-AMD (i.e., 4 weeks post-SCGx). Although RPE mitochondrial mass was preserved, their function, which was higher at the temporal than at the nasal RPE in control eyes, was significantly decreased at 4 weeks post-SCGx at the same region. Mitochondria were bigger, more elongated, and with denser cristae at the temporal RPE from control eyes. Exclusively at the temporal RPE, SCGx severely affected mitochondrial morphology and dynamics, together with the levels of phosphorylated AMPK (p-AMPK). AMPK activation with metformin restored RPE p-AMPK levels, and mitochondrial dynamics, structure, and function at 4 weeks post-SCGx, as well as visual function and RPE/outer retina structure at 10 weeks post-SCGx. These results demonstrate a key role of the temporal RPE mitochondrial homeostasis as an early target for NE-AMD-induced damage, and that pharmacological AMPK activation could preserve mitochondrial morphology, dynamics, and function, and, consequently, avoid the functional and structural damage induced by NE-AMD.},
}
@article {pmid38578329,
year = {2024},
author = {Soomro, T and Georgiadis, O and Coffey, PJ and da Cruz, L},
title = {Safety, structure and function five years after hESC-RPE patch transplantation in acute neovascular AMD with submacular haemorrhage.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {9},
pages = {3057-3060},
pmid = {38578329},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence ; *Wet Macular Degeneration/diagnosis ; *Visual Acuity ; *Retinal Hemorrhage/diagnosis/etiology/surgery ; Acute Disease ; *Retinal Pigment Epithelium/transplantation/pathology ; Male ; Follow-Up Studies ; Female ; Fluorescein Angiography/methods ; Aged ; Human Embryonic Stem Cells/transplantation ; Time Factors ; Patient Acuity ; Stem Cell Transplantation/methods ; },
}
@article {pmid38577865,
year = {2024},
author = {Biswas, A and Kumar, S and Choudhury, AD and Bisen, AC and Sanap, SN and Agrawal, S and Mishra, A and Verma, SK and Kumar, M and Bhatta, RS},
title = {Polymers and their engineered analogues for ocular drug delivery: Enhancing therapeutic precision.},
journal = {Biopolymers},
volume = {115},
number = {4},
pages = {e23578},
doi = {10.1002/bip.23578},
pmid = {38577865},
issn = {1097-0282},
support = {3/1/3(2)/OPH/2020-NCD-II//Indian Council of Medical Research/ ; },
mesh = {Humans ; *Drug Delivery Systems/methods ; *Eye Diseases/drug therapy ; *Polymers/chemistry ; Hyaluronic Acid/chemistry ; Animals ; Administration, Ophthalmic ; Eye/metabolism/drug effects ; Drug Carriers/chemistry ; },
abstract = {Ocular drug delivery is constrained by anatomical and physiological barriers, necessitating innovative solutions for effective therapy. Natural polymers like hyaluronic acid, chitosan, and gelatin, alongside synthetic counterparts such as PLGA and PEG, have gained prominence for their biocompatibility and controlled release profiles. Recent strides in polymer conjugation strategies have enabled targeted delivery through ligand integration, facilitating tissue specificity and cellular uptake. This versatility accommodates combined drug delivery, addressing diverse anterior (e.g., glaucoma, dry eye) and posterior segment (e.g., macular degeneration, diabetic retinopathy) afflictions. The review encompasses an in-depth exploration of each natural and synthetic polymer, detailing their individual advantages and disadvantages for ocular drug delivery. By transcending ocular barriers and refining therapeutic precision, these innovations promise to reshape the management of anterior and posterior segment eye diseases.},
}
@article {pmid38577852,
year = {2024},
author = {Chaurasiya, SK and Singh, M and Chander, A and Pushkar, R},
title = {Comment: Low Vision Referral Patterns in Intermediate Age-Related Macular Degeneration.},
journal = {Current eye research},
volume = {49},
number = {7},
pages = {782-783},
doi = {10.1080/02713683.2024.2337297},
pmid = {38577852},
issn = {1460-2202},
mesh = {Humans ; *Referral and Consultation ; *Macular Degeneration/diagnosis/physiopathology ; *Vision, Low/physiopathology/diagnosis/etiology ; Visual Acuity/physiology ; },
}
@article {pmid38576880,
year = {2024},
author = {Thippayajan, S and Oupathumpanont, O and Parnsakhorn, S},
title = {Improving the Nutritional Value of Natural Cheese Analog Products Using Nam Dok Mai Mango.},
journal = {Preventive nutrition and food science},
volume = {29},
number = {1},
pages = {63-69},
pmid = {38576880},
issn = {2287-1098},
abstract = {This research aimed to (1) discover the appropriate formula for the production of Nam Dok Mai mango cheese analog products and (2) study the physical, nutritional, microbial, and sensory properties of the produced Nam Dok Mai mango cheese analogs. To investigate the appropriate formula, the factors studied included the pH value of Nam Dok Mai mango juice (2.50 or 3.00) and the proportion of salted butter (18.0% or 19.5%) and carrageenan (0.8% or 0.9%). The study was conducted by using the factorials in a completely randomized design experiment. It was found that the optimal formula for the Nam Dok Mai mango cheese analog consisted of 33.0% casein protein, 46.0% Nam Dok Mai mango juice (pH 3), 19.5% salted butter, 0.5% sodium citrate, 0.9% carrageenan, and 0.1% xanthan gum. Regarding the nutritional value, it was found that the Nam Dok Mai cheese analog (100 g) contained 129.00 μg of β-carotene, 148.41 mg of calcium, 1.15 g of dietary fiber, and 21.50 μg of vitamin A. Sixty-eight percent of consumers scored it as "moderate" for overall acceptability. However, when the consumers received the nutritional information of the Nam Dok Mai mango cheese analog, many (76%) said they would buy the product because it contains vitamin A that important for vision and eye health. Consuming enough vitamin A helps protect against certain eye diseases, such as age-related macular degeneration. This is consistent with the lifestyles of people today who use their eyes too hard, such as staring at a computer screen and cell phones all day.},
}
@article {pmid38576540,
year = {2024},
author = {Landowski, M and Gogoi, P and Ikeda, S and Ikeda, A},
title = {Roles of transmembrane protein 135 in mitochondrial and peroxisomal functions - implications for age-related retinal disease.},
journal = {Frontiers in ophthalmology},
volume = {4},
number = {},
pages = {},
pmid = {38576540},
issn = {2674-0826},
support = {P30 EY016665/EY/NEI NIH HHS/United States ; S10 OD023526/OD/NIH HHS/United States ; T32 EY027721/EY/NEI NIH HHS/United States ; F32 EY032766/EY/NEI NIH HHS/United States ; R01 EY022086/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; },
abstract = {Aging is the most significant risk factor for age-related diseases in general, which is true for age-related diseases in the eye including age-related macular degeneration (AMD). Therefore, in order to identify potential therapeutic targets for these diseases, it is crucial to understand the normal aging process and how its mis-regulation could cause age-related diseases at the molecular level. Recently, abnormal lipid metabolism has emerged as one major aspect of age-related symptoms in the retina. Animal models provide excellent means to identify and study factors that regulate lipid metabolism in relation to age-related symptoms. Central to this review is the role of transmembrane protein 135 (TMEM135) in the retina. TMEM135 was identified through the characterization of a mutant mouse strain exhibiting accelerated retinal aging and positional cloning of the responsible mutation within the gene, indicating the crucial role of TMEM135 in regulating the normal aging process in the retina. Over the past decade, the molecular functions of TMEM135 have been explored in various models and tissues, providing insights into the regulation of metabolism, particularly lipid metabolism, through its action in multiple organelles. Studies indicated that TMEM135 is a significant regulator of peroxisomes, mitochondria, and their interaction. Here, we provide an overview of the molecular functions of TMEM135 which is crucial for regulating mitochondria, peroxisomes, and lipids. The review also discusses the age-dependent phenotypes in mice with TMEM135 perturbations, emphasizing the importance of a balanced TMEM135 function for the health of the retina and other tissues including the heart, liver, and adipose tissue. Finally, we explore the potential roles of TMEM135 in human age-related retinal diseases, connecting its functions to the pathobiology of AMD.},
}
@article {pmid38573348,
year = {2024},
author = {Madheswaran, G and Shenoy, S and Ganeshrao, SB and SVe, R},
title = {Mesopic and scotopic perimetry correlation in age-related macular degeneration using open perimetric interface and standard automated perimetry.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {9},
pages = {3053-3056},
pmid = {38573348},
issn = {1435-702X},
mesh = {Humans ; *Visual Field Tests/methods ; *Visual Fields/physiology ; *Macular Degeneration/diagnosis/physiopathology/complications ; Mesopic Vision/physiology ; Aged ; Night Vision/physiology ; Female ; Male ; Visual Acuity/physiology ; },
}
@article {pmid38572848,
year = {2024},
author = {Felder-Schmittbuhl, MP and Hicks, D and Ribelayga, CP and Tosini, G},
title = {Melatonin in the mammalian retina: Synthesis, mechanisms of action and neuroprotection.},
journal = {Journal of pineal research},
volume = {76},
number = {3},
pages = {e12951},
doi = {10.1111/jpi.12951},
pmid = {38572848},
issn = {1600-079X},
support = {/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Melatonin/metabolism ; Neuroprotection ; Retina/metabolism ; Receptors, Melatonin/metabolism ; Retinal Cone Photoreceptor Cells/metabolism ; Receptor, Melatonin, MT1/metabolism ; Receptor, Melatonin, MT2/metabolism ; Mammals/metabolism ; },
abstract = {Melatonin is an important player in the regulation of many physiological functions within the body and in the retina. Melatonin synthesis in the retina primarily occurs during the night and its levels are low during the day. Retinal melatonin is primarily synthesized by the photoreceptors, but whether the synthesis occurs in the rods and/or cones is still unclear. Melatonin exerts its influence by binding to G protein-coupled receptors named melatonin receptor type 1 (MT1) and type 2 (MT2). MT1 and MT2 receptors activate a wide variety of signaling pathways and both receptors are present in the vertebrate photoreceptors where they may form MT1/MT2 heteromers (MT1/2h). Studies in rodents have shown that melatonin signaling plays an important role in the regulation of retinal dopamine levels, rod/cone coupling as well as the photopic and scotopic electroretinogram. In addition, melatonin may play an important role in protecting photoreceptors from oxidative stress and can protect photoreceptors from apoptosis. Critically, melatonin signaling is involved in the modulation of photoreceptor viability during aging and other studies have implicated melatonin in the pathogenesis of age-related macular degeneration. Hence melatonin may represent a useful tool in the fight to protect photoreceptors-and other retinal cells-against degeneration due to aging or diseases.},
}
@article {pmid38571282,
year = {2024},
author = {Gurubaran, IS and Watala, C and Kostanek, J and Szczepanska, J and Pawlowska, E and Kaarniranta, K and Blasiak, J},
title = {PGC-1α regulates the interplay between oxidative stress, senescence and autophagy in the ageing retina important in age-related macular degeneration.},
journal = {Journal of cellular and molecular medicine},
volume = {28},
number = {8},
pages = {e18051},
pmid = {38571282},
issn = {1582-4934},
support = {296840//Academy of Finland Grants/ ; 333302//Academy of Finland Grants/ ; 2017/27/B/NZ3/00872//National Science Center Poland/ ; //Sigrig Juselius Foundation/ ; },
mesh = {Mice ; Animals ; *Antioxidants/metabolism ; Mitochondria/metabolism ; Oxidative Stress ; Aging ; *Macular Degeneration/metabolism ; Autophagy/genetics ; Retinal Pigment Epithelium/metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism ; },
abstract = {We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1α protein, and nuclear factor erythroid 2 like 2 (NFE2L2) gene, exhibited some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1α in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defence, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defence also contributed to that discrimination. A bioinformatic analysis showed that PGC-1α might coordinate the interplay between genes encoding proteins involved in antioxidant defence, senescence and autophagy in the ageing retina. These data support importance of PGC-1α in AMD pathogenesis and confirm the utility of mice with PGC-1α knockout as an animal model to study AMD pathogenesis.},
}
@article {pmid38571248,
year = {2024},
author = {Hormel, TT and Liang, GB and Wei, X and Guo, Y and Gao, M and Wang, J and Huang, D and Bailey, ST and Hwang, TS and Jia, Y},
title = {Visualizing features with wide-field volumetric OCT angiography.},
journal = {Optics express},
volume = {32},
number = {6},
pages = {10329-10347},
pmid = {38571248},
issn = {1094-4087},
support = {R01 EY023285/EY/NEI NIH HHS/United States ; P30 EY010572/EY/NEI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; R01 EY024544/EY/NEI NIH HHS/United States ; R01 EY031394/EY/NEI NIH HHS/United States ; R01 EY035410/EY/NEI NIH HHS/United States ; R01 EY027833/EY/NEI NIH HHS/United States ; T32 EY023211/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Vessels/pathology ; Fluorescein Angiography ; Tomography, Optical Coherence/methods ; Retina ; *Diabetic Retinopathy ; },
abstract = {Optical coherence tomography (OCT) and its extension OCT angiography (OCTA) have become essential clinical imaging modalities due to their ability to provide depth-resolved angiographic and tissue structural information non-invasively and at high resolution. Within a field of view, the anatomic detail available is sufficient to identify several structural and vascular pathologies that are clinically relevant for multiple prevalent blinding diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and vein occlusions. The main limitation in contemporary OCT devices is that this field of view is limited due to a fundamental trade-off between system resolution/sensitivity, sampling density, and imaging window dimensions. Here, we describe a swept-source OCT device that can capture up to a 12 × 23-mm field of view in a single shot and show that it can identify conventional pathologic features such as non-perfusion areas outside of conventional fields of view. We also show that our approach maintains sensitivity sufficient to visualize novel features, including choriocapillaris morphology beneath the macula and macrophage-like cells at the inner limiting membrane, both of which may have implications for disease.},
}
@article {pmid38568620,
year = {2024},
author = {Iezzi, R and Scruggs, BA and Gandhi, J and Zenti, FN and Shafi, N and Berger, A and Marmorstein, AD},
title = {Early Choriocapillaris Loss in a Porcine Model of RPE Cell Debridement Precedes Pathology That Simulates Advanced Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {4},
pages = {8},
pmid = {38568620},
issn = {1552-5783},
mesh = {Female ; Swine ; Animals ; Debridement ; *Macular Degeneration/diagnosis/surgery ; *Geographic Atrophy/diagnosis ; Sus scrofa ; Retina ; Choroid ; *Choroidal Neovascularization/diagnosis/surgery ; },
abstract = {PURPOSE: No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling.<br><br>METHODS: Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1&#xa0;month, 2&#xa0;months, 3&#xa0;months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2&#xa0;months (n = 3), 3&#xa0;months (n = 2), or 6&#xa0;months (n = 2) after surgery.<br><br>RESULTS: RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point.<br><br>CONCLUSIONS: Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.},
}
@article {pmid38568619,
year = {2024},
author = {Ruffini, A and Casalucci, A and Cara, C and Ethier, CR and Repetto, R},
title = {Drug Distribution After Intravitreal Injection: A Mathematical Model.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {4},
pages = {9},
pmid = {38568619},
issn = {1552-5783},
support = {R01 EY033361/EY/NEI NIH HHS/United States ; },
mesh = {Intravitreal Injections ; *Anterior Eye Segment ; Biological Transport ; *Intraocular Pressure ; Models, Theoretical ; },
abstract = {PURPOSE: Intravitreal injection of drugs is commonly used for treatment of chorioretinal ocular pathologies, such as age-related macular degeneration. Injection causes a transient increase in the intraocular volume and, consequently, of the intraocular pressure (IOP). The aim of this work is to investigate how intravitreal flow patterns generated during the post-injection eye deflation influence the transport and distribution of the injected drug.<br><br>METHODS: We present mathematical and computational models of fluid motion and mass transport in the vitreous chamber during the transient phase after injection, including the previously unexplored effects of globe deflation as ocular volume decreases.<br><br>RESULTS: During eye globe deflation, significant fluid velocities are generated within the vitreous chamber, which can possibly contribute to drug transport. Pressure variations within the eye globe are small compared to IOP.<br><br>CONCLUSIONS: Even if significant fluid velocities are generated in the vitreous chamber after drug injection, these are found to have negligible overall effect on drug distribution.},
}
@article {pmid38567515,
year = {2024},
author = {Hansman, DS and Ma, Y and Thomas, D and Smith, JR and Casson, RJ and Peet, DJ},
title = {Metabolic reprogramming of the retinal pigment epithelium by cytokines associated with age-related macular degeneration.},
journal = {Bioscience reports},
volume = {44},
number = {4},
pages = {},
pmid = {38567515},
issn = {1573-4935},
support = {//University of Adelaide Biochemistry trust Fund/ ; 1099932//National Health and Medical Research Council (NHMRC)/ ; },
mesh = {Humans ; Rats ; Animals ; *Retinal Pigment Epithelium/metabolism ; Metabolic Reprogramming ; Cytokines/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; *Macular Degeneration/genetics/metabolism ; Lactates/metabolism ; },
abstract = {The complex metabolic relationship between the retinal pigment epithelium (RPE) and photoreceptors is essential for maintaining retinal health. Recent evidence indicates the RPE acts as an adjacent lactate sink, suppressing glycolysis in the epithelium in order to maximize glycolysis in the photoreceptors. Dysregulated metabolism within the RPE has been implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss. In the present study, we investigate the effects of four cytokines associated with AMD, TNFα, TGF-β2, IL-6, and IL-1β, as well as a cocktail containing all four cytokines, on RPE metabolism using ARPE-19 cells, primary human RPE cells, and ex vivo rat eyecups. Strikingly, we found cytokine-specific changes in numerous metabolic markers including lactate production, glucose consumption, extracellular acidification rate, and oxygen consumption rate accompanied by increases in total mitochondrial volume and ATP production. Together, all four cytokines could potently override the constitutive suppression of glycolysis in the RPE, through a mechanism independent of PI3K/AKT, MEK/ERK, or NF-κB. Finally, we observed changes in glycolytic gene expression with cytokine treatment, including in lactate dehydrogenase subunit and glucose transporter expression. Our findings provide new insights into the metabolic changes in the RPE under inflammatory conditions and highlight potential therapeutic targets for AMD.},
}
@article {pmid38564612,
year = {2024},
author = {Weng, CC and Chi, SC and Lin, TC and Huang, YM and Chou, YB and Hwang, DK and Chen, SJ},
title = {Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.},
journal = {PloS one},
volume = {19},
number = {4},
pages = {e0301096},
pmid = {38564612},
issn = {1932-6203},
mesh = {Humans ; Aged ; Aged, 80 and over ; Treatment Outcome ; Follow-Up Studies ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Tomography, Optical Coherence ; Visual Acuity ; Intravitreal Injections ; *Retinal Detachment/etiology ; Vision Disorders/complications ; *Macular Degeneration/drug therapy/epidemiology/complications ; China ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy/complications ; *Antibodies, Monoclonal, Humanized ; },
abstract = {This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.},
}
@article {pmid38563162,
year = {2024},
author = {Pastora, LE and Namburu, NS and Arora, K and Christov, PP and Wilson, JT},
title = {STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.},
journal = {ACS applied bio materials},
volume = {7},
number = {8},
pages = {4867-4878},
pmid = {38563162},
issn = {2576-6422},
support = {T32 DK101003/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; },
mesh = {*Membrane Proteins/metabolism/antagonists &amp; inhibitors ; *Nanoparticles/chemistry ; Animals ; Mice ; Inflammation/drug therapy ; Humans ; Biocompatible Materials/chemistry/pharmacology ; Particle Size ; Materials Testing ; Nucleotidyltransferases/antagonists &amp; inhibitors/metabolism ; Signal Transduction/drug effects ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; },
abstract = {Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.},
}
@article {pmid38560652,
year = {2024},
author = {Garmo, V and Zhao, X and Ng, CD and Near, A and Banerji, T and Wada, K and Oderda, G and Brixner, D and Biskupiak, J and Ali, FS and Khanani, AM and Menezes, A and Abbass, IM},
title = {The Association of Retinal Disease with Vision Impairment and Functional Status in Medicare Patients.},
journal = {Journal of health economics and outcomes research},
volume = {11},
number = {1},
pages = {94-102},
pmid = {38560652},
issn = {2327-2236},
abstract = {Background: The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. Objectives: This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. Methods: Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported "a little trouble seeing" (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported "a lot of trouble seeing/blindness" (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio [OR], 5.39; 95% confidence interval, 4.06-7.16; P < .001) and difficulties with iADLs (odds ratio, 1.41; 95% confidence interval, 1.11-1.80; P = .005); no differences were observed for DME or RVO vs control. After adjusting for age, sex, race/ethnicity, poverty status, comorbidities, and other relevant covariates, nAMD, DME, and RVO were not significantly associated with anxiety/depression, falls, or fractures. Discussion: Patients with nAMD or DME were more likely to report severe visual impairment than those without VTRDs, although only those with nAMD were more likely to be diagnosed with vision loss. Conclusions: Patients with nAMD continue to experience more vision impairment and worse functional status compared with a similar population of Medicare beneficiaries despite availability of therapies like antivascular endothelial growth factor to treat retinal disease.},
}
@article {pmid38560277,
year = {2024},
author = {Wagner, SK and Patel, PJ and Huemer, J and Khalid, H and Stuart, KV and Chu, CJ and Williamson, DJ and Struyven, RR and Romero-Bascones, D and Foster, PJ and Khawaja, AP and Petzold, A and Balaskas, K and Cortina-Borja, M and Chapple, I and Dietrich, T and Rahi, JS and Denniston, AK and Keane, PA and , },
title = {Periodontitis and Outer Retinal Thickness: a Cross-Sectional Analysis of the United Kingdom Biobank Cohort.},
journal = {Ophthalmology science},
volume = {4},
number = {4},
pages = {100472},
pmid = {38560277},
issn = {2666-9145},
support = {MR/T000953/1/MRC_/Medical Research Council/United Kingdom ; MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; MR/T033371/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {PURPOSE: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease.<br><br>DESIGN: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank.<br><br>PARTICIPANTS: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging.<br><br>METHODS: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery.<br><br>MAIN OUTCOME MEASURES: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses.<br><br>RESULTS: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P < 0.001). On average, those with very severe periodontitis were hyperopic (0.05 &#xb1; 2.27 diopters) while those unaffected were myopic (-0.29 &#xb1; 2.40 diopters, P < 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 &#x3bc;m, 95% confidence interval [CI],&#xa0;-0.97 to&#xa0;-0.12; P&#xa0;= 0.022) but there was no difference in RPE-BM thickness (0.00 &#x3bc;m, 95% CI,&#xa0;-0.12 to 0.13; P&#xa0;= 0.97). The association between PRL thickness and very severe periodontitis was modified by age (P < 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 &#x3bc;m, 95% CI,&#xa0;-1.85 to&#xa0;-0.53; P < 0.001) but not among those aged < 60 years.<br><br>CONCLUSIONS: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38559826,
year = {2023},
author = {Palfi Salavat, MC and Șeclăman, EP and Mușat, AA and Borugă, M and Patoni, C and Popescu, MN and Teodorescu, OE and Mușat, O and Popescu Patoni, SI},
title = {Aflibercept Versus Bevacizumab as First-Line Therapy in Age-Related Macular Degeneration.},
journal = {Current health sciences journal},
volume = {49},
number = {4},
pages = {503-509},
pmid = {38559826},
issn = {2067-0656},
abstract = {AMD (age-related macular degeneration) is the main cause of central vision loss in the population over 60 years old. AMD does not affect peripheral vision and complete blindness does not occur, instead, central vision is affected both for distance and for near. The purpose of this study is to evaluate the neovascular form of AMD treatment and compare ocular and systemic effects after intravitreal injection of aflibercept, respectively after bevacizumab when administered in comparable dosages and regimens. We conducted a retrospective, single-center study from June 2021 to December 2022 and enrolled 20 patients with neovascular AMD who had not received any prior treatment for this condition. We randomly assigned them to two groups of 10: group one received aflibercept and group two received bevacizumab as intravitreal injections under aseptic conditions. We excluded 2 patients who did not meet the criteria and ended up with two groups of 9 patients who received monocular treatment. We gave the patients 3 monthly injections of anti-VEGF agent and followed them up at 1 month, 3 months, and 9 months after the treatment. We assessed their visual acuity, intraocular pressure and OCT appearance at each follow-up visit. The primary outcome was visual acuity. All 18 patients included in the study reported an improvement in visual acuity after the intervention. When comparing the two anti-VEGF agents, data revealed the effect of aflibercept was prompter and more long-lasting. Areas of retinal ischemia appeared in both cases. However, they were observed faster in the case of patients treated with aflibercept. Thus, neovascular AMD is a disease that occurs with age, it can be early detected by OCT and slowed the progression to central blindness with intravitreal treatment.},
}
@article {pmid38559365,
year = {2024},
author = {Chandrasekaran, PR and Chan, HH and Tan, TE and Ibrahim, FNI and Zhao, J and Teo, KYC},
title = {A case of secondary multiple evanescent white dot syndrome in a patient with preexisting wet age-related macular degeneration.},
journal = {American journal of ophthalmology case reports},
volume = {34},
number = {},
pages = {102016},
pmid = {38559365},
issn = {2451-9936},
abstract = {PURPOSE: To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration.<br><br>OBSERVATION: A 75-year-old male on treat and extend regimen for wet age-related macular degeneration (AMD) presented with a sudden loss of vision and saw central dark shadow in the right eye (RE) for a duration of 1 week. There was no significant history preceding the visual loss. Examination showed a visual acuity (VA) of counting fingers at 1&#xa0;meter in the right eye and 20/25 in the left eye. Anterior segment examination was unremarkable with dilated fundus examination showing a clear vitreous, tortuous blood vessel, a hyperemic disc and fibrosis at the macula. The left eye (LE) examination was unremarkable. Optical Coherence Tomography (OCT) showed fibrosis due to the previous wet AMD and hyperreflective excrescences projecting from the retinal pigment epithelium (RPE) outside of the old area of wet AMD. Fundus Fluorescein Angiogram (FFA) showed hyperfluorescent spots in a wreath-like pattern increasing in intensity in the early phase and showing late staining towards the late phase while Indocyanine green angiography (ICGA) did not clearly delineate the lesions. Fundus autofluorescence (FAF) revealed hyper Autofluorescence (AF) at the posterior pole. Optical Coherence Tomography Angiography (OCTA) revealed a flow reduction in the choriocapillaris of the affected area. Basic blood investigations with Venereal Disease Research Laboratory (VDRL), syphilitic IgM and IgG antibodies, Quantiferon TB gold test, complete renal function tests and liver function tests were performed. All the blood investigations were within normal limits and the workup for syphilis and tuberculosis was negative. The patient was started on 1mg/kg body weight of oral prednisolone (after the non-response to low dose of oral steroids) with the diagnosis of secondary multiple evanescent white dot syndrome (MEWDS) secondary to wet AMD. The patient was followed up every weekly and the last visit showed improvement in visual acuity to 20/50 with resolution of lesions on FAF and OCT macula.<br><br>CONCLUSION AND IMPORTANCE: Secondary MEWDS is extremely rare and unique in terms of its presentation and its association with preexisting chorioretinal disease where there is damage to the choriocapillaris- Bruch's membrane-RPE complex. This case report highlights one such rare case scenario and how multimodal imaging helps in the diagnosis, management and follow-up of patients with secondary MEWDS.},
}
@article {pmid38559206,
year = {2024},
author = {Bergmans, S and Noel, NCL and Masin, L and Harding, EG and Krzywańska, AM and De Schutter, JD and Ayana, R and Hu, CK and Arckens, L and Ruzycki, PA and MacDonald, RB and Clark, BS and Moons, L},
title = {Age-related dysregulation of the retinal transcriptome in African turquoise killifish.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38559206},
issn = {2692-8205},
support = {DP2 AG077431/AG/NIA NIH HHS/United States ; P30 EY002687/EY/NEI NIH HHS/United States ; },
abstract = {Age-related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short-lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single-cell RNA-sequencing (scRNA-seq) of three age groups (6-, 12-, and 18-week-old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age-related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterised, confirming the presence of all typical vertebrate retinal cell types. Data integration from age-matched samples between the bulk and scRNA-seq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasises the value of the fast-ageing killifish in elucidating molecular signatures in age-associated retinal disease and vision decline. This study contributes to the understanding of how age-related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age-related pathologies.},
}
@article {pmid38558979,
year = {2024},
author = {Motipally, SI and Kolson, DR and Guan, T and Kolandaivelu, S},
title = {Aberrant lipid accumulation and retinal pigmental epithelium dysfunction in PRCD-deficient mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.03.08.584131},
pmid = {38558979},
issn = {2692-8205},
support = {R01 EY028959/EY/NEI NIH HHS/United States ; },
abstract = {Progressive Rod-Cone Degeneration (PRCD) is an integral membrane protein found in photoreceptor outer segment (OS) disc membranes and its function remains unknown. Mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans and multiple dog breeds. PRCD-deficient models exhibit decreased levels of cholesterol in the plasma. However, potential changes in the retinal cholesterol remain unexplored. In addition, impaired phagocytosis observed in these animal models points to potential deficits in the retinal pigment epithelium (RPE). Here, using a Prcd [-/-] murine model we investigated the alterations in the retinal cholesterol levels and impairments in the structural and functional integrity of the RPE. Lipidomic and immunohistochemical analyses show a 5-fold increase in the levels of cholesteryl esters (C.Es) and accumulation of neutral lipids in the PRCD-deficient retina, respectively, indicating alterations in total retinal cholesterol. Longitudinal fundus and spectral domain optical coherence tomography (SD-OCT) examinations showed focal lesions and RPE hyperreflectivity. Strikingly, the RPE of Prcd [-/-] mice exhibited age-related pathological features such as neutral lipid deposits, lipofuscin accumulation, Bruch's membrane (BrM) thickening and drusenoid focal deposits, mirroring an Age-related Macular Degeneration (AMD)-like phenotype. We propose that the extensive lipofuscin accumulation likely impairs lysosomal function, leading to the defective phagocytosis observed in Prcd [-/-] mice. Our findings support the dysregulation of retinal cholesterol homeostasis in the absence of PRCD. Further, we demonstrate that progressive photoreceptor degeneration in Prcd [-/-] mice is accompanied by progressive structural and functional deficits in the RPE, which likely exacerbates vision loss over time.},
}
@article {pmid38558091,
year = {2024},
author = {Künzel, SE and Pompös, IM and Flesch, LTM and Frentzel, DP and Knecht, VA and Winkler, S and Skosyrski, S and Rübsam, A and Dreher, F and Kociok, N and Schütte, M and Dubrac, A and Lange, B and Yaspo, ML and Lehrach, H and Strauß, O and Joussen, AM and Zeitz, O},
title = {Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {4},
pages = {5},
pmid = {38558091},
issn = {1552-5783},
mesh = {Humans ; Mice ; Animals ; Vascular Endothelial Growth Factor Receptor-1 ; Saccharin/therapeutic use ; Vascular Endothelial Growth Factor A/genetics/metabolism ; Sweetening Agents ; Cross-Sectional Studies ; Chromatography, Liquid ; Tandem Mass Spectrometry ; *Choroidal Neovascularization/metabolism ; *Macular Degeneration/metabolism ; RNA, Messenger/genetics ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {PURPOSE: We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment.<br><br>METHODS: In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line.<br><br>RESULTS: Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression.<br><br>CONCLUSIONS: Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.},
}
@article {pmid38558077,
year = {2024},
author = {Tokunaga, T and Takegawa, R and Ueta, Y and Manabe, Y and Fushiki, H},
title = {Assessing fall risk and equilibrium function in patients with age-related macular degeneration and glaucoma: An observational study.},
journal = {PloS one},
volume = {19},
number = {4},
pages = {e0301377},
pmid = {38558077},
issn = {1932-6203},
mesh = {Humans ; Aged ; Middle Aged ; Dizziness/complications ; Visual Acuity ; Visual Fields ; *Glaucoma/complications ; Scotoma ; *Macular Degeneration/pathology ; },
abstract = {BACKGROUND: Falls in older adults are a significant public health concern, and age-related macular degeneration (AMD) and glaucoma have been identified as potential visual risk factors. This study was designed to assess equilibrium function, fall risk, and fall-related self-efficacy (an individual's belief in their capacity to act in ways necessary to reach specific goals) in patients with AMD and glaucoma.<br><br>METHODS: This observational study was performed at the Otorhinolaryngology Department of Shinseikai Toyama Hospital. The cohort comprised 60 participants (AMD; n = 30; median age, 76.0 years; and glaucoma; n = 30; median age, 64.5 years). Visual acuity and visual fields were assessed using the decimal best-corrected visual acuity and Humphrey visual field tests, respectively. The evaluation metrics included pathological eye movement analysis, bedside head impulse test, single-leg upright test, eye-tracking test, optokinetic nystagmus, and posturography. Furthermore, we administered questionnaires for fall risk determinants including the Dizziness Handicap Inventory, Activities-Specific Balance Confidence Scale, Falls Efficacy Scale-International, and Hospital Anxiety and Depression Scale. The collected data were analyzed using descriptive statistics, and Spearman's correlation analysis was employed to examine the interrelations among the equilibrium function, fall risk, and other pertinent variables.<br><br>RESULTS: Most participants exhibited standard outcomes in equilibrium function evaluations. Visual acuity and field deficits had a minimal impact on subjective dizziness manifestations, degree of disability, and fall-related self-efficacy. Both groups predominantly showed high self-efficacy. No significant correlation was observed between visual acuity or field deficits and body equilibrium function or fall risk. However, greater peripheral visual field impairment was associated with a tendency for sensory reweighting from visual to somatosensory.<br><br>CONCLUSION: Self-efficacy was higher and fall risk was relatively lower among patients with mild-to-moderate visual impairment, with a tendency for sensory reweighting from visual to somatosensory in those with greater peripheral visual field impairment. Further studies are required to validate these findings.},
}
@article {pmid38556186,
year = {2024},
author = {Cennamo, G and Rinaldi, M and Malvone, E and Costagliola, C},
title = {Choroidal Thickness and brolucizumab intravitreal injection: Cause or effect of intraocular inflammation?.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {47},
number = {},
pages = {104072},
doi = {10.1016/j.pdpdt.2024.104072},
pmid = {38556186},
issn = {1873-1597},
mesh = {Humans ; *Intravitreal Injections ; Male ; Female ; *Choroid/pathology/drug effects/diagnostic imaging ; *Tomography, Optical Coherence/methods ; *Antibodies, Monoclonal, Humanized/adverse effects/administration &amp; dosage/therapeutic use ; Aged ; Wet Macular Degeneration/drug therapy ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Middle Aged ; },
abstract = {PURPOSE: to analyze the structural changes of choroidal thickness in patients with brolucizumab-related exudative vitritis after intravitreal injection, using EDI-OCT.<br><br>METHODS: One hundred eyes of one hundred patients, affected by exudative age related-macular degeneration treated with brolucizumab intravitreal injection between January 2022 and august 2023 at Eye clinic of University of Federico II Naples, were enrolled. All eyes underwent macular examination using Enhanced Deep Imaging-OCT (Spectralis, Heidelberg Engineering inc.) preoperatively and at each postoperative check (1, 3, 6, 12 months). Anterior segment evaluation at slit lamp before and after injection was performed.<br><br>RESULTS: Of the 100 treated eyes, 4 showed inflammatory signs related to exudative vitreitis, with inflammation signs at slit lamp examination and confirmed by OCT and B scan ecography. EDI-OCT revealed, in all of these 4 patients, a significant increase of choroidal thickness compared to baseline.<br><br>CONCLUSION: choroidal thickness could be correlated in the inflammatory response generated in patients undergoing treatment with brolucizumab.},
}
@article {pmid38555699,
year = {2024},
author = {Xu, H and Yi, C and Chen, M},
title = {The complement pathway as a therapeutic target for neovascular age-related macular degeneration-mediated subretinal fibrosis.},
journal = {Current opinion in pharmacology},
volume = {76},
number = {},
pages = {102448},
doi = {10.1016/j.coph.2024.102448},
pmid = {38555699},
issn = {1471-4973},
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Fibrosis ; Animals ; *Complement System Proteins/metabolism ; Complement Activation/drug effects ; Retina/pathology/metabolism/drug effects ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the elderly in developed countries. Intravitreal injection of VEGF inhibitors is the mainstream therapy for nAMD, although nearly 50% of the patients do not respond or respond poorly to the therapy. One of the main reasons for the poor outcome of the therapy is the development of subretinal macular fibrosis, a process of excessive deposition of extracellular matrix proteins around the diseased blood vessels. Currently, there is no medication to prevent or treat the condition. Here, we discussed recent advances in the pathogenesis of nAMD-mediated macular fibrosis, with a focus on the role of the complement system. We further proposed approaches to target the complement system for the management of macular fibrosis and highlighted the area of further research for future clinical applications of complement-based therapy.},
}
@article {pmid38555635,
year = {2024},
author = {Veritti, D and Sarao, V and Martinuzzi, D and Menzio, S and Lanzetta, P},
title = {Submacular hemorrhage during neovascular age-related macular degeneration: a meta-analysis and meta-regression on the use of tPA and anti-VEGFs.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {3},
pages = {191-202},
pmid = {38555635},
issn = {1423-0267},
abstract = {BACKGROUND: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) precipitates rapid visual decline and impacts quality of life. Treatments vary, but combined recombinant tissue plasminogen activator (tPA) and anti-vascular endothelial growth factor (anti-VEGF) therapy has gained prominence as a viable treatment option.<br><br>OBJECTIVES: This study aims to evaluate the efficacy of the combination of tPA and anti-VEGF.<br><br>METHODS: We conducted a systematic review meta-analysis following PRISMA guidelines, focusing on studies examining tPA and anti-VEGF therapy in SMH secondary to nAMD. Outcomes measured were change in best-corrected visual acuity (BCVA) and success rate of SMH displacement. Meta-regression assessed the relative efficacy of intravitreal and subretinal delivery.<br><br>RESULTS: Out of 257 initial reports, 22 studies involving 29 patient populations met inclusion criteria. Our analysis showed significant improvement in BCVA and a high rate of successful SMH displacement with combined tPA and anti-VEGF therapy. No significant differences were found between subretinal and intravitreal tPA administration. Furthermore, when evaluating the effects of subretinal versus intravitreal anti-VEGF administration in patients treated with subretinal tPA, the results indicated similar efficacy.<br><br>CONCLUSIONS: Combined tPA and anti-VEGF therapy is effective in managing SMH in nAMD patients, significantly improving visual acuity and SMH displacement. The location of tPA and anti-VEGF delivery did not significantly impact outcomes.},
}
@article {pmid38554726,
year = {2024},
author = {Campochiaro, PA and Avery, R and Brown, DM and Heier, JS and Ho, AC and Huddleston, SM and Jaffe, GJ and Khanani, AM and Pakola, S and Pieramici, DJ and Wykoff, CC and Van Everen, S},
title = {Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study.},
journal = {Lancet (London, England)},
volume = {403},
number = {10436},
pages = {1563-1573},
doi = {10.1016/S0140-6736(24)00310-6},
pmid = {38554726},
issn = {1474-547X},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Genetic Therapy/methods ; Ranibizumab ; Treatment Outcome ; *Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection. We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD.<br><br>METHODS: For this open-label, multiple-cohort, multicentre, phase 1/2a, dose-escalation study conducted at eight sites in the USA, we enrolled participants with nAMD aged 50-89 years who had previously been treated with anti-VEGF injections into five cohorts (with five different doses of RGX-314). To be eligible, participants had to have macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the centre subfield, be pseudophakic (after cataract removal), and have a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 for the first participant in each cohort and between 20/40 and 20/400 for others. Subretinal injection of RGX-314 was done without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Cohort 1 received 3&#x2009;&#xd7;&#x2009;10[9] genome copies per eye, cohort 2 received 1&#x2009;&#xd7;&#x2009;10[10], and cohort 3 received 6&#x2009;&#xd7;&#x2009;10[10]. Two additional dose cohorts (cohort 4: 1&#xb7;6&#x2009;&#xd7;&#x2009;10[11]; cohort 5: 2&#xb7;5&#x2009;&#xd7;&#x2009;10[11]) were added. Participants were seen 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The primary outcome was safety of RGX-314 delivered by subretinal injection up to week 26. This analysis includes all 42 patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT03066258.<br><br>FINDINGS: Between May 12, 2017, and May 21, 2019, we screened 110 patients for eligibility and enrolled 68. 42 participants demonstrated the required anatomic response to intravitreal ranibizumab and then received a single RGX-314 injection (dose range 3&#x2009;&#xd7;&#x2009;10[9] to 2&#xb7;5&#x2009;&#xd7;&#x2009;10[11] genome copies per eye) and were followed up for 2 years. There were 20 serious adverse events in 13 participants, of which one was possibly related to RGX-314: pigmentary changes in the macula with severe vision reduction 12 months after injection of RGX-314 at a dose of 2&#xb7;5&#x2009;&#xd7;&#x2009;10[11] genome copies per eye. Asymptomatic pigmentary changes were seen in the inferior retinal periphery several months after subretinal injection of RGX-314 most commonly at doses of 6&#x2009;&#xd7;&#x2009;10[10] genome copies per eye or higher. There were no clinically determined immune responses or inflammation beyond that expected following routine vitrectomy. Doses of 6&#x2009;&#xd7;&#x2009;10[10] genome copies or higher resulted in sustained concentrations of RGX-314 protein in aqueous humour and stable or improved BCVA and central retinal thickness with few or no supplemental anti-VEGF-A injections in most participants.<br><br>INTERPRETATION: Subretinal delivery of RGX-314 was generally well tolerated with no clinically recognised immune responses. RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, and reduce treatment burden after a single administration. Results from this study informed the pivotal programme to evaluate RGX-314 in patients with nAMD.<br><br>FUNDING: RegenxBio.},
}
@article {pmid38554724,
year = {2024},
author = {Rakoczy, EP},
title = {The promise of long-term treatment for neovascular age-related macular degeneration.},
journal = {Lancet (London, England)},
volume = {403},
number = {10436},
pages = {1517-1519},
doi = {10.1016/S0140-6736(24)00428-8},
pmid = {38554724},
issn = {1474-547X},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/drug therapy ; Tomography, Optical Coherence ; Retrospective Studies ; },
}
@article {pmid38553490,
year = {2024},
author = {Wolfram, L and Gimpel, C and Schwämmle, M and Clark, SJ and Böhringer, D and Schlunck, G},
title = {The impact of substrate stiffness on morphological, transcriptional and functional aspects in RPE.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {7488},
pmid = {38553490},
issn = {2045-2322},
mesh = {Humans ; Bruch Membrane ; Extracellular Matrix/genetics ; Cell Culture Techniques ; *Macular Degeneration ; RNA, Messenger/genetics ; *MicroRNAs/genetics ; Retinal Pigment Epithelium ; },
abstract = {Alterations in the structure and composition of Bruch's membrane (BrM) and loss of retinal pigment epithelial (RPE) cells are associated with various ocular diseases, notably age-related macular degeneration (AMD) as well as several inherited retinal diseases (IRDs). We explored the influence of stiffness as a major BrM characteristic on the RPE transcriptome and morphology. ARPE-19 cells were plated on soft (E = 30 kPa) or stiff (E = 80 kPa) polyacrylamide gels (PA gels) or standard tissue culture plastic (TCP). Next-generation sequencing (NGS) data on differentially expressed small RNAs (sRNAs) and messenger RNAs (mRNAs) were validated by qPCR, immunofluorescence or western blotting. The microRNA (miRNA) fraction of sRNAs grew with substrate stiffness and distinct miRNAs such as miR-204 or miR-222 were differentially expressed. mRNA targets of differentially expressed miRNAs were stably expressed, suggesting a homeostatic effect of miRNAs. mRNA transcription patterns were substrate stiffness-dependent, including components of Wnt/beta-catenin signaling, Microphthalmia-Associated Transcription Factor (MITF) and Dicer. These findings highlight the relevance of mechanical properties of the extracellular matrix (ECM) in cell culture experiments, especially those focusing on ECM-related diseases, such as AMD.},
}
@article {pmid38552931,
year = {2024},
author = {de Carlo Forest, TE and Gill, Z and Lisker-Cervantes, A and Gnanaraj, R and Grove, N and Patnaik, JL and Lynch, AM and Palestine, AG and Mathias, M and Manoharan, N and Mandava, N},
title = {Association Between Quantitative and Qualitative Imaging Biomarkers and Geographic Atrophy Growth Rate.},
journal = {American journal of ophthalmology},
volume = {264},
number = {},
pages = {168-177},
pmid = {38552931},
issn = {1879-1891},
support = {UL1 TR002535/TR/NCATS NIH HHS/United States ; UM1 TR004399/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy/diagnosis ; Female ; Male ; Prospective Studies ; *Tomography, Optical Coherence/methods ; Aged ; *Fluorescein Angiography/methods ; *Biomarkers ; *Multimodal Imaging ; Aged, 80 and over ; Visual Acuity/physiology ; Follow-Up Studies ; Disease Progression ; Middle Aged ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Fundus Oculi ; Registries ; },
abstract = {PURPOSE: Investigate associations between geographic atrophy (GA) growth rate and multimodal imaging biomarkers and patient demographics in patients with advanced non-neovascular age-related macular degeneration (nnAMD).<br><br>DESIGN: Prospective cohort study.<br><br>METHODS: One hundred twenty-one eyes of 66 patients with advanced nnAMD with GA enrolled in the University of Colorado AMD Registry from August 2014 to June 2021, with follow-up through June 2023. Multimodal images were reviewed by two graders for imaging biomarkers at enrollment. GA growth rate and square-root transformed (SQRT) GA growth rate were measured between enrollment and final visit. Associations between the outcome SQRT GA growth rate and imaging biomarkers, baseline GA lesions characteristics, and patient demographics were evaluated.<br><br>RESULTS: Average GA growth rate was 1.430 mm[2]/year and SQRT GA growth rate was 0.268 mm/year over a mean of 3.7 years. SQRT GA growth rate was positively associated with patient age (P = .010) and female sex (0.035), and negatively associated with body mass index (0.041). After adjustment for these demographic factors, SQRT GA growth rate was positively associated with presence of non-exudative subretinal fluid (P < .001), non-exudative subretinal hyperreflective material (P = .037), and incomplete retinal pigment epithelium and outer retina atrophy (P = .022), and negatively associated with subfoveal choroidal thickness (P = .031) and presence of retinal pseudocysts (P = .030). Larger baseline GA size at enrollment was associated with faster GA growth rate (P = .002) but not SQRT GA growth rate.<br><br>CONCLUSIONS: Select patient demographic factors and basic clinically-relevant imaging biomarkers were associated with GA growth rate. These biomarkers may guide patient selection when considering treating GA patients with novel therapeutics.},
}
@article {pmid38552713,
year = {2024},
author = {Zhao, X and Hu, L and Liu, G and Yin, X and Gong, Q and Li, Y and Li, Q and Zhou, Y and Sun, Y and Guo, C and Du, Z},
title = {Fibronectin binds integrin α5β1 to regulate macular neovascularization through the Wnt/β-catenin signaling pathway.},
journal = {Experimental eye research},
volume = {242},
number = {},
pages = {109880},
doi = {10.1016/j.exer.2024.109880},
pmid = {38552713},
issn = {1096-0007},
mesh = {Animals ; *Fibronectins/metabolism ; *Integrin alpha5beta1/metabolism/genetics ; Mice ; *Wnt Signaling Pathway/physiology ; *Disease Models, Animal ; *Mice, Inbred C57BL ; Cell Movement/physiology ; Blotting, Western ; Macaca mulatta ; Retinal Neovascularization/metabolism/pathology ; beta Catenin/metabolism ; Immunohistochemistry ; Real-Time Polymerase Chain Reaction ; Male ; Cells, Cultured ; },
abstract = {Age-related macular degeneration (AMD) is a progressive, degenerative disease of the macula. The formation of macular neovascularization (MNV) and subretinal fibrosis of AMD is the most classic cause of the loss of vision in older adults worldwide. While the underlying causes of MNV and subretinal fibrosis remain elusive, the common feature of many common retinal diseases is changes the proportions of protein deposition in extracellular matrix (ECM) when compared to normal tissue. In ECM, fibronectin (FN) is a crucial component and plays a pivotal part not only in fibrotic diseases but also in the process of angiogenesis. The study aims to understand the role of ligand FN and its common integrin receptor α5β1 on MNV, and to understand the molecular mechanism involved. To study this, the laser-induced MNV mouse model and the rhesus macaque choroid-retinal endothelial cell line (RF/6A) chemical hypoxia mode were established, and the FN-α5β1 expression levels were detected by immunohistochemistry (IHC) and quantitative real-time PCR analysis (qRT-PCR). Fibronectin expression was silenced using small interfering RNA (siRNA) targeting FN. The tube formation and vitro scratch assays were used to assess the ability to form blood vessels and cell migration. To measure the formation of MNV, immunofluorescence, and Western blot assays were used. These results revealed that the expressions of FN and integrin α5β1 were distinctly increased in the laser-induced MNV mouse model and in the RF/6A cytochemically induced hypoxia model, and the expression tendency was identical. After the use of FN siRNA, the tube formation and migration abilities of the RF/6A cells were lower, the ability of endothelial cells to proliferate was confined and the scope of damage caused by the laser in animal models was significantly cut down. In addition, FN gene knockdown dramatically inhibited the expression of Wnt/β-catenin signal. The interaction of FN with the integrin receptor α5β1 in the constructed model, which may act through the Wnt/β-catenin signaling pathway, was confirmed in this study. In conclusion, FN may be a potential new molecular target for the prevention and treatment of subretinal fibrosis and MNV.},
}
@article {pmid38551696,
year = {2024},
author = {Üney, G and Hazırolan, D and Ünlü, N and Candan, &#xd6;},
title = {Pro re nata anti-VEGF treatment in pachychoroid neovasculopathy compared with age-related macular degeneration based on optical coherence tomography.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {164},
pmid = {38551696},
issn = {1573-2630},
mesh = {Humans ; *Ranibizumab ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Intravitreal Injections ; *Macular Degeneration/diagnosis/drug therapy ; Retrospective Studies ; },
abstract = {PURPOSE: To compare anti-vascular endothelial growth factor (anti-VEGF) treatment in pachychoroid neovasculopathy (PNV) and age related macular degeneration (AMD).<br><br>METHODS: Cases having pro re nata (PRN) anti-VEGF treatment for choroidal neovascularization were reviewed and grouped as PNV and AMD. Groups were compared according to central foveal thickness (CFT), best corrected visual acuity (BCVA), and total injection over 12&#xa0;months. The correlation of beginning choroidal thickness, CFT, and BCVA with final BCVA was analyzed.<br><br>RESULTS: Forty-seven PNV and 65 AMD cases were reviewed. Both the PNV group (p&#x2009;=&#x2009;0.0001) and the AMD group (p&#x2009;=&#x2009;0.003) had a significant improvement in BCVA and a significant decrease in CFT (p&#x2009;=&#x2009;0.0001). However, BCVA was better at the 3-, 6-, and 12-month follow-up in PNV (p&#x2009;=&#x2009;0.003, 0.002, 0.02). No significant CFT difference was observed between groups. The total number of injections was 5.7&#x2009;&#xb1;&#x2009;1.7 for PNV and 5.2&#x2009;&#xb1;&#x2009;1.5 for AMD (p&#x2009;=&#x2009;0.09). Beginning BCVA was positively correlated with final BCVA in both groups.<br><br>CONCLUSION: The PRN treatment regimen was effective for PNV and AMD in terms of visual and anatomical outcomes. Visual response was better in PNV with PRN treatment with the same number of injections.},
}
@article {pmid38551188,
year = {2024},
author = {Sharma, A and Kumar, N and Parachuri, N and Loewenstein, A and Bandello, F and Kuppermann, BD},
title = {Global experience of faricimab in clinical settings - a review.},
journal = {Expert opinion on biological therapy},
volume = {24},
number = {4},
pages = {263-268},
doi = {10.1080/14712598.2024.2336087},
pmid = {38551188},
issn = {1744-7682},
mesh = {Humans ; *Antibodies, Bispecific/therapeutic use/adverse effects ; Angiogenesis Inhibitors/adverse effects/therapeutic use ; Macular Degeneration/drug therapy ; Treatment Outcome ; },
abstract = {INTRODUCTION: Faricimab is a bispecific antibody that acts to reduce neoangiogenesis in exudative retinal vascular disorders. It is approved for use in neovascular age-related macular degeneration and diabetic macular edema. We review the published efficacy and safety of faricimab in clinical settings.<br><br>AREAS COVERED: A comprehensive literature review was conducted. Based on the 14 published real-world studies, 1127 patients (1204 eyes) were treated with faricimab. The majority of studies (14) included pre-treated patients. Most studies (13) showed central macular thickness improvement. However visual acuity improved in only half of the studies analyzed. Four studies demonstrated an extension of the treatment. Only 4 eyes (0.33%) reported intraocular inflammation and 3 eyes (0.24%) reported retinal pigment epithelial tear.<br><br>EXPERT OPINION: The clinical experience with faricimab to date has the potential to provide a stable visual outcome with reduced treatment burden in cases that are resistant to other approved anti-VEGF agents. There are no major safety concerns based on this data analysis.},
}
@article {pmid38546400,
year = {2025},
author = {Savastano, A and Sammarco, LA and Francione, G and Sasso, P and Rizzo, S},
title = {SCLERAL FIXATION OF THE SMALLER-INCISION NEW-GENERATION IMPLANTABLE MINIATURE TELESCOPE USING GORE-TEX SUTURE.},
journal = {Retinal cases &amp; brief reports},
volume = {19},
number = {3},
pages = {410-412},
doi = {10.1097/ICB.0000000000001572},
pmid = {38546400},
issn = {1937-1578},
mesh = {Humans ; *Lens Implantation, Intraocular/methods ; *Lenses, Intraocular ; *Polytetrafluoroethylene ; *Sclera/surgery ; *Suture Techniques/instrumentation ; *Sutures ; *Telescopes ; Vitrectomy/methods ; },
abstract = {PURPOSE: In this case report, the authors describe a surgical technique for scleral fixation of the smaller-incision new-generation implantable miniature telescope (SING-IMT). Using this surgical technique, the patient's eye that undergoes surgery for the SING-IMT could still have a safe SING IMT implant despite the anatomical conditions of the capsular bag or in cases of intraoperative complications.<br><br>METHODS: The surgery was performed at Policlinico A. Gemelli, Rome, Italy. The patient's eye underwent a first surgery for an artificial intraocular lens explant and SING-IMT implant at the same time. The authors observed SING IMT dislocation into the vitreous chamber 90 days after surgery. Therefore, they carried out a 23-gauge vitrectomy, and after SING IMT recovery from the vitreous chamber, they fixed one of its haptic to the sclera using an 8.0 Gore-Tex suture.<br><br>CONCLUSION: Scleral fixation of SING-IMT haptics might be useful in eyes with dislocated or not stable SING IMT. The authors believe that reporting our experience can help surgeons fix SING IMT in complicated cases where a capsular bag rupture or disinsertion (like our case) can cause SING IMT decentration or worse its drop into the vitreous chamber. They speculate that the Gore-Tex suture could assure firm fixation of the SING IMT and could reduce the risk of recurrent dislocations.},
}
@article {pmid38545630,
year = {2024},
author = {Fei, Y and Jo, JJ and Chen, S and Ledesma-Gil, G and Otero-Marquez, O and Mordechaev, E and Le, B and Tong, Y and Tai, K and Lema, G and Rosen, RB and Agarwal, VV and Smith, RT},
title = {Quantifying cardiac dysfunction and valvular heart disease associated with subretinal drusenoid deposits in age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {34},
number = {6},
pages = {2038-2044},
doi = {10.1177/11206721241244413},
pmid = {38545630},
issn = {1724-6016},
mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; *Retinal Drusen/diagnosis ; Aged ; *Heart Valve Diseases/complications/diagnosis/physiopathology ; Aged, 80 and over ; *Echocardiography ; *Macular Degeneration/diagnosis/complications/physiopathology ; Tomography, Optical Coherence/methods ; Multimodal Imaging ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND/AIMS: Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent valvular heart disease (VHD) and reduced systemic perfusion via cardiac index (CI).<br><br>METHODS: Post-hoc analysis of cross-sectional study. 200 intermediate AMD (iAMD) subjects were assigned by masked readers to two groups: SDD (with or without drusen) and drusen (only) based on multimodal ophthalmic imaging. 65 transthoracic echocardiograms (TTEs) reports were available for cardiologist evaluation of VHD severity of the four cardiac valves and the presences of precursor lesions of aortic sclerosis (ASc) and mitral annular calcification (MAC). Necessary parameters to calculate CI were also obtained. Univariate testing was performed using Fisher's Exact test and t-test.<br><br>RESULTS: 82.6% (19/23) of the iAMD subjects with at least one moderate/severe VHD had concurrent SDDs (p&#x2009;=&#x2009;0.0040). All cases of aortic regurgitation (6/6, p&#x2009;=&#x2009;0.0370) and mitral regurgitation (13/13, p&#x2009;=&#x2009;0.0004) were found with coexisting SDDs. Stenotic VHD was not significantly associated with SDDs, however 70.7% of subjects with ASc (29/41, p&#x2009;=&#x2009;0.0108) and 76.0% of subjects with MAC (19/25, 0.0377) had coexisting SDDs. CI was available in 48 subjects and was significantly below normal levels in the SDD cohort (mean CI SDD 1.95&#x2009;&#xb1;&#x2009;0.60&#x2005;L/min/m[2], non-SDD 2.71&#x2009;&#xb1;&#x2009;0.73&#x2005;L/min/m[2], p&#x2009;=&#x2009;0.0004).<br><br>CONCLUSIONS: Several specific VHDs have been found associated with the SDD form of AMD. Decreased systemic perfusion as measured by CI was also associated with SDDs, which supports a perfusion hypothesis of SDD pathogenesis. Further research is warranted to understand the relationship between cardiovascular disease and SDDs.},
}
@article {pmid38543208,
year = {2024},
author = {Carlà, MM and Savastano, MC and Boselli, F and Giannuzzi, F and Rizzo, S},
title = {Ranibizumab Port Delivery System in Neovascular Age-Related Macular Degeneration: Where Do We Stand? Overview of Pharmacokinetics, Clinical Results, and Future Directions.},
journal = {Pharmaceutics},
volume = {16},
number = {3},
pages = {},
pmid = {38543208},
issn = {1999-4923},
abstract = {The ranibizumab (RBZ) port delivery system (PDS) is a device designed to continuously deliver RBZ in the vitreous chamber for the treatment of neovascular age-related macular degeneration (nAMD). It is implanted during a surgical procedure and can provide sustained release of the medication for several months. This review, updated to January 2024, focuses on past clinical studies as well as current and forthcoming trials looking into a PDS with RBZ. In the phase 2 LADDER trial, the mean time to first refill of a PDS with RBZ 100 mg/mL was 15.8 months, with the pharmacokinetic (PK) profile showing a sustained concentration of RBZ in the blood and aqueous humor. More recently, a PDS with RBZ (100 mg/mL) refilled every 24 weeks was shown to be non-inferior to a monthly intravitreal injection (IVI) with RBZ (0.5 mg) over 40 and 92 weeks in the phase 3 ARCHWAY trial. The refill every 24 weeks allowed for a RBZ vitreous exposure within the concentration range of monthly intravitreal injections (IVIs), and the expected half-life (106 days) was comparable with the in vitro results. Nonetheless, vitreous hemorrhage and endophthalmitis were more common side effects in PDS patients. In conclusion, a PDS continuously delivering RBZ has a clinical effectiveness level comparable with IVI treatment. However, a greater frequency of unfavorable occurrences highlights the need for procedure optimization for a wider adoption. Ongoing trials and possible future approaches need to be addressed.},
}
@article {pmid38542204,
year = {2024},
author = {Huang, YC and Liao, WL and Lin, HJ and Huang, YT and Chang, YW and Liu, TY and Chen, YC and Weng, AL and Tsai, FJ},
title = {Identification of Genetic Variants for Risk Prediction and Early Diagnosis of Age-Related Macular Degeneration in the Taiwanese Population.},
journal = {International journal of molecular sciences},
volume = {25},
number = {6},
pages = {},
pmid = {38542204},
issn = {1422-0067},
mesh = {Aged ; Humans ; *Proteins/genetics ; Genome-Wide Association Study ; *Macular Degeneration/diagnosis/epidemiology/genetics ; High-Temperature Requirement A Serine Peptidase 1/genetics ; Polymorphism, Single Nucleotide ; Early Diagnosis ; Genetic Predisposition to Disease ; Risk Factors ; Genotype ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. The prevalence and phenotypes of AMD differ among populations, including between people in Taiwan and other regions. We performed a genome-wide association study to identify genetic variants and to develop genetic models to predict the risk of AMD development and progression in the Taiwanese population. In total, 4039 patients with AMD and 16,488 non-AMD controls (aged ≥ 65 years) were included. We identified 31 AMD-associated variants (p < 5 × 10[-8]) on chromosome 10q26, surrounding PLEKHA1-ARMS2-HTRA1. Two genetic models were constructed using the clump and threshold method. Model 1 included the single nucleotide polymorphism rs11200630 and showed a 1.31-fold increase in the risk of AMD per risk allele (95% confidence interval (CI) = 1.20-1.43, p < 0.001). In model 2, 1412 single-nucleotide polymorphisms were selected to construct a polygenic risk score (PRS). Individuals with the top 5% PRS had a 1.40-fold higher AMD risk compared with that of individuals with a PRS in the bottom quartile (95% CI = 1.04-1.89, p = 0.025). Moreover, the PRS in the upper quartile was related to a decreased age at AMD diagnosis by 0.62 years (95% CI = -1.15, -0.09, p = 0.023). Both genetic models provide useful predictive power for populations at high risk of AMD, affording a basis for identifying patients requiring close follow-up and early intervention.},
}
@article {pmid38541834,
year = {2024},
author = {Fukuda, Y and Notomi, S and Shiose, S and Maehara, Y and Kiyohara, K and Hashimoto, S and Kano, K and Ishikawa, K and Hisatomi, T and Sonoda, KH},
title = {Wide-Field Choroidal Thickness Analysis after Half-Fluence Photodynamic Therapy Combined with Intravitreal Aflibercept Injection in Pachychoroid Neovasculopathy.},
journal = {Journal of clinical medicine},
volume = {13},
number = {6},
pages = {},
pmid = {38541834},
issn = {2077-0383},
support = {JP21K09702//Japan Society for the Promotion of Science/ ; },
abstract = {Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Methods: Seventeen eyes with PNV that underwent half-fluence PDT with an adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9-18 mm from the fovea. The <9 and 9-18 mm subfields were divided into four quadrants. Results: Choroidal thickness in each subfield decreased significantly after half-fluence PDT (p < 0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9 mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. Conclusions: Half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.},
}
@article {pmid38541191,
year = {2024},
author = {Karska-Basta, I and Pociej-Marciak, W and Żuber-Łaskawiec, K and Markiewicz, A and Chrząszcz, M and Romanowska-Dixon, B and Kubicka-Trząska, A},
title = {Diagnostic Challenges in Inflammatory Choroidal Neovascularization.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {3},
pages = {},
pmid = {38541191},
issn = {1648-9144},
mesh = {Humans ; Vascular Endothelial Growth Factor A ; *Choroiditis/complications/diagnosis ; *Choroidal Neovascularization/diagnosis/complications ; Inflammation/complications ; Tomography, Optical Coherence/methods ; Hypoxia ; },
abstract = {Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.},
}
@article {pmid38540785,
year = {2024},
author = {Hitti-Malin, RJ and Panneman, DM and Corradi, Z and Boonen, EGM and Astuti, G and Dhaenens, CM and Stöhr, H and Weber, BHF and Sharon, D and Banin, E and Karali, M and Banfi, S and Ben-Yosef, T and Glavač, D and Farrar, GJ and Ayuso, C and Liskova, P and Dudakova, L and Vajter, M and Ołdak, M and Szaflik, JP and Matynia, A and Gorin, MB and Kämpjärvi, K and Bauwens, M and De Baere, E and Hoyng, CB and Li, CHZ and Klaver, CCW and Inglehearn, CF and Fujinami, K and Rivolta, C and Allikmets, R and Zernant, J and Lee, W and Podhajcer, OL and Fakin, A and Sajovic, J and AlTalbishi, A and Valeina, S and Taurina, G and Vincent, AL and Roberts, L and Ramesar, R and Sartor, G and Luppi, E and Downes, SM and van den Born, LI and McLaren, TL and De Roach, JN and Lamey, TM and Thompson, JA and Chen, FK and Tracewska, AM and Kamakari, S and Sallum, JMF and Bolz, HJ and Kayserili, H and Roosing, S and Cremers, FPM},
title = {Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.},
journal = {Biomolecules},
volume = {14},
number = {3},
pages = {},
pmid = {38540785},
issn = {2218-273X},
support = {P30 EY000331/EY/NEI NIH HHS/United States ; R01 EY028954/EY/NEI NIH HHS/United States ; R01 EY028203/EY/NEI NIH HHS/United States ; R01 EY029315/EY/NEI NIH HHS/United States ; P30 EY019007/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Mutation ; Penetrance ; Pedigree ; *Macular Degeneration/genetics ; Retina ; Phenotype ; ATP-Binding Cassette Transporters/genetics ; Eye Proteins ; Cadherin Related Proteins ; Nerve Tissue Proteins/genetics ; },
abstract = {Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.},
}
@article {pmid38540673,
year = {2024},
author = {Fu, Y and Zhang, Z and Webster, KA and Paulus, YM},
title = {Treatment Strategies for Anti-VEGF Resistance in Neovascular Age-Related Macular Degeneration by Targeting Arteriolar Choroidal Neovascularization.},
journal = {Biomolecules},
volume = {14},
number = {3},
pages = {},
pmid = {38540673},
issn = {2218-273X},
support = {R01 EY034325/EY/NEI NIH HHS/United States ; R01 EY033000/EY/NEI NIH HHS/United States ; P30 EY002520/EY/NEI NIH HHS/United States ; 1R01EY033805 1R01EY034325 1R01EY033000 2P30EY002520 P30 EY007003/NH/NIH HHS/United States ; R01 EY033805/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; Vascular Endothelial Growth Factor A ; *Macular Degeneration/drug therapy/metabolism ; *Choroidal Neovascularization/drug therapy ; Vascular Endothelial Growth Factors ; Cholesterol ; },
abstract = {Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declining responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.},
}
@article {pmid38538983,
year = {2024},
author = {Dabbur, O and Koestel, E and El Habhab, A and Ahmad, T and Abry, F and Sauer, A and Bourcier, T},
title = {Visual outcomes after cataract surgery in monocular compared to binocular patients: a case-control study.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {162},
pmid = {38538983},
issn = {1573-2630},
mesh = {Humans ; Case-Control Studies ; *Cataract/complications ; *Glaucoma, Open-Angle/complications ; Treatment Outcome ; *Cataract Extraction ; *Phacoemulsification ; Blindness ; Vision, Binocular ; },
abstract = {PURPOSE: We aimed to identify ocular comorbidities and reasons of blindness in monocular patients and to compare visual outcomes of cataract surgery between monocular and binocular patients.<br><br>METHODS: A single-center case-control study was conducted between November 2011 and May 2019 to compare consecutive series of patients needing cataract surgery in Strasbourg University Hospitals, France. Cases were patients with permanent monocular vision loss. Controls were binocularly sighted patients. All patients underwent cataract surgery using phacoemulsification technique. Chart analysis included demographic data, medical history, and surgical determinants data. Student's t tests and Fisher's exact tests were the main methods used for statistical analysis.<br><br>RESULTS: Each group included 80 patients. The mean age at the time of surgery was significantly higher in monocular than binocular patients (77 vs. 71&#xa0;years, p&#x2009;<&#x2009;0.001). Thirty-two monocular patients (40%) had ocular comorbidities, compared to only 19 (23%) in the control group (p&#x2009;<&#x2009;0.05). The leading cause of monocular status was amblyopia caused by strabismus (22 patients, 27.5%). Age-related macular degeneration, open-angle glaucoma, and diabetic retinopathy were the three main ocular comorbidities that were observed in the monocular group. Monocular patients had significantly lower visual acuity than the control group (p&#x2009;<&#x2009;0.01) before and after cataract surgery. Conversely, improvement in visual acuity after surgery was not statistically different between groups (p&#x2009;=&#x2009;0.054). There was no statistically significant difference in the rate of surgical complications between groups (p&#x2009;=&#x2009;0.622).<br><br>CONCLUSIONS: This study illustrates that cataract surgery in monocular patients is not more complicated than in binocular patients, but that it is significantly delayed.},
}
@article {pmid38538345,
year = {2024},
author = {Nguyen, J and Brantley, MA and Schwartz, SG},
title = {Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians.},
journal = {Frontiers in bioscience (Scholar edition)},
volume = {16},
number = {1},
pages = {3},
doi = {10.31083/j.fbs1601003},
pmid = {38538345},
issn = {1945-0524},
support = {P30EY014801//NIH Core Center/ ; GR004596-1//Research to Prevent Blindness-Unrestricted/ ; },
mesh = {Humans ; *Proteins ; *Macular Degeneration/drug therapy/genetics ; Dietary Supplements ; High-Temperature Requirement A Serine Peptidase 1/genetics ; Vascular Endothelial Growth Factors/genetics/therapeutic use ; Polymorphism, Single Nucleotide ; Risk Factors ; },
abstract = {Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 (ARMS2/HTRA1). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.},
}
@article {pmid38537669,
year = {2024},
author = {Tong, M and Bai, Y and Han, X and Kong, L and Ren, L and Zhang, L and Li, X and Yao, J and Yan, B},
title = {Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in choroidal neovascularization model.},
journal = {Experimental eye research},
volume = {242},
number = {},
pages = {109877},
doi = {10.1016/j.exer.2024.109877},
pmid = {38537669},
issn = {1096-0007},
mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/metabolism/pathology ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Disease Models, Animal ; *Choroid/pathology/metabolism ; *Single-Cell Analysis ; *Macrophages/metabolism/pathology ; Transcriptome ; Mice, Inbred C57BL ; Fibroblasts/metabolism/pathology ; Endothelial Cells/metabolism/pathology ; Cell Communication/physiology ; Wet Macular Degeneration/genetics/metabolism ; Gene Expression Profiling ; },
abstract = {Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD) and a major contributor to vision loss in nAMD cases. However, the identification of specific cell types associated with nAMD remains challenging. Herein, we performed single-cell sequencing to comprehensively explore the cellular diversity and understand the foundational components of the retinal pigment epithelium (RPE)/choroid complex. We unveiled 10 distinct cell types within the RPE/choroid complex. Notably, we observed significant heterogeneity within endothelial cells (ECs), fibroblasts, and macrophages, underscoring the intricate nature of the cellular composition in the RPE/choroid complex. Within the EC category, four distinct clusters were identified and EC cluster 0 was tightly associated with choroidal neovascularization. We identified five clusters of fibroblasts actively involved in the pathogenesis of nAMD, influencing fibrotic responses, angiogenic effects, and photoreceptor function. Additionally, three clusters of macrophages were identified, suggesting their potential roles in regulating the progression of nAMD through immunomodulation and inflammation regulation. Through CellChat analysis, we constructed a complex cell-cell communication network, revealing the role of EC clusters in interacting with fibroblasts and macrophages in the context of nAMD. These interactions were found to govern angiogenic effects, fibrotic responses, and inflammatory processes. In summary, this study reveals noteworthy cellular heterogeneity in the RPE/choroid complex and provides valuable insights into the pathogenesis of CNV. These findings will open up potential avenues for deep understanding and targeted therapeutic interventions in nAMD.},
}
@article {pmid38536685,
year = {2025},
author = {Yang, XH and Liao, HJ and Sun, PY and Ma, J and Wang, B and He, Y and Xue, LG and Su, LM and Wang, BJ},
title = {MCD-LightGBM System for Intelligent Analyzing Heterogeneous Clinical Drug Therapeutic Effects.},
journal = {IEEE journal of biomedical and health informatics},
volume = {29},
number = {6},
pages = {3894-3905},
doi = {10.1109/JBHI.2024.3379432},
pmid = {38536685},
issn = {2168-2208},
mesh = {Humans ; Algorithms ; *Boosting Machine Learning Algorithms ; Machine Learning ; *Drug Therapy ; },
abstract = {Causal effect estimation of individual heterogeneity is a core issue in the field of causal inference, and its application in medicine poses an active and challenging problem. In high-risk decision-making domain such as healthcare, inappropriate treatments can have serious negative impacts on patients. Recently, machine learning-based methods have been proposed to improve the accuracy of causal effect estimation results. However, many of these methods concentrate on estimating causal effects of continuous outcome variables under binary intervention conditions, and give less consideration to multivariate intervention conditions or discrete outcome variables, thus limiting their scope of application. To tackle this issue, we combine the double machine learning framework with Light Gradient Boosting Machine (LightGBM) and propose a double LightGBM model. This model can estimate binary causal effects more accurately and in less time. Two cyclic structures were added to the model. Data correction method was introduced and improved to transform discrete outcome variables into continuous outcome variables. Multivariate Cyclic Double LightGBM model (MCD-LightGBM) was proposed to intelligently estimate multivariate treatment effects. A visual human-computer interaction system for heterogeneous causal effect estimation was designed, which can be applied to different types of data. This paper reports that the system improved the Logarithm of the Minimum Angle of Resolution (LogMAR) of visual acuity change after Vascular Endothelial Growth Factor (anti-VEGF) treatment in patients with diabetic macular degeneration. The improvement was observed in two clinical problems, from 0.05 to 0.33, and the readmission rate of diabetic patients after cure was reduced from 48.4% to 10.5%. The results above demonstrate the potential of the proposed system in predicting heterogeneous clinical drug treatment effects.},
}
@article {pmid38536516,
year = {2024},
author = {Zhang, M and Zhang, R and Zhao, X and Ma, Z and Xin, J and Xu, S and Guo, D},
title = {The role of oxidative stress in the pathogenesis of ocular diseases: an overview.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {454},
pmid = {38536516},
issn = {1573-4978},
mesh = {Humans ; Reactive Oxygen Species/metabolism ; *Antioxidants/metabolism ; Eye/metabolism ; Oxidative Stress ; *Glaucoma/drug therapy ; },
abstract = {Dysregulation of oxidative stress serves as a pivotal predisposing or exacerbating factor in the intricate development of numerous pathological processes and diseases. In recent years, substantial evidence has illuminated the crucial role of reactive oxygen species (ROS) in many fundamental cellular functions, including proliferation, inflammation, apoptosis, and gene expression. Notably, producing free radicals within ROS profoundly impacts a wide range of biomolecules, such as proteins and DNA, instigating cellular damage and impairing vital cellular functions. Consequently, oxidative stress emerges as a closely intertwined factor across diverse disease spectra. Remarkably, the pathogenesis of several eye diseases, including age-related macular degeneration, glaucoma, and diabetic retinopathy, manifests an intrinsic association with oxidative stress. In this comprehensive review, we briefly summarize the recent progress in elucidating the intricate role of oxidative stress in the development of ophthalmic diseases, shedding light on potential therapeutic avenues and future research directions.},
}
@article {pmid38535942,
year = {2024},
author = {Han, Z and Zhao, C and Li, Y and Xiao, M and Yang, Y and Zhao, Y and Liu, C and Liu, J and Li, P},
title = {Ambient Air Pollution and Vision Disorder: A Systematic Review and Meta-Analysis.},
journal = {Toxics},
volume = {12},
number = {3},
pages = {},
pmid = {38535942},
issn = {2305-6304},
support = {2020M670667//China Postdoctoral Science Foundation/ ; 22ZYCGCG00920, 21YFSNSN00030//Tianjin Research Program/ ; },
abstract = {The effects of air pollution on physical health are well recognized, with many studies revealing air pollution's effects on vision disorder, yet no relationship has been established. Therefore, a meta-analysis was carried out in this study to investigate the connection between vision disorder and ambient particles (diameter ≤ 2.5 µm (PM2.5), diameter ≤ 10 µm (PM10)) and gaseous pollutants (nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), Ozone (O3)). Twelve relevant studies published by 26 February 2024 were identified in three databases. A pooled odds ratios (ORs) of 95% confidence intervals (CIs) were obtained using random-effects meta-analysis models. Meta-analysis results revealed that for every 10 µg/m[3] increase in PM2.5 and NO2 exposure, a substantially higher incidence of vision disorder was observed (OR = 1.10; 95% CI: 1.01, 1.19; OR = 1.08, 95% CI: 1.00, 1.16). No significant correlation existed between exposure to PM10, SO2 and CO and vision disorder. However, O3 exposure was negatively associated with vision disorder. In addition, subgroup analyses revealed that PM2.5 exposure was significantly correlated with the risk of glaucoma and age-related macular degeneration and that children and adolescents were more susceptible to NO2 and PM2.5 than adults. Overall, exposure to air pollutants, especially PM2.5 and NO2, may increase the incidence of vision disorder.},
}
@article {pmid38534576,
year = {2024},
author = {Zhang, C and Wang, J and Wu, H and Fan, W and Li, S and Wei, D and Song, Z and Tao, Y},
title = {Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives.},
journal = {Gels (Basel, Switzerland)},
volume = {10},
number = {3},
pages = {},
pmid = {38534576},
issn = {2310-2861},
support = {No. 82101162//National Natural Science Foundation of China/ ; No. 21JCQN002 and 21JCZD002//Basic Research Project of Henan Eye Institute/ ; No. YXKC2021027//Health science and Technology Innovation Outstanding Young talents training program of Henan Province/ ; },
abstract = {Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.},
}
@article {pmid38534392,
year = {2024},
author = {Yi, Y and Pyun, SH and Kim, CY and Yun, G and Kang, E and Heo, S and Ullah, I and Lee, SK},
title = {Eye Drop with Fas-Blocking Peptide Attenuates Age-Related Macular Degeneration.},
journal = {Cells},
volume = {13},
number = {6},
pages = {},
pmid = {38534392},
issn = {2073-4409},
support = {2022R1A2C1011348//Korea Research Foundation/ ; },
mesh = {Humans ; Mice ; Animals ; Rabbits ; *Retinal Degeneration ; Ophthalmic Solutions/therapeutic use ; *Macular Degeneration/metabolism ; Peptides/therapeutic use ; Inflammation ; },
abstract = {Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.},
}
@article {pmid38532410,
year = {2024},
author = {Liu, D and Du, J and Xie, H and Tian, H and Lu, L and Zhang, C and Xu, GT and Zhang, J},
title = {Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration.},
journal = {Journal of neuroinflammation},
volume = {21},
number = {1},
pages = {75},
pmid = {38532410},
issn = {1742-2094},
support = {23YF1434200//Shanghai Sailing Program/ ; 82301222//National Natural Science Foundation of China/ ; 82171062//National Natural Science Foundation of China/ ; 2023YFC2506100//National Key Research and Development Program of China/ ; U2267220//Joint Funds of the National Natural Science Foundation of China/ ; },
mesh = {Humans ; Male ; Animals ; Mice ; *beta Catenin/metabolism ; Wnt-5a Protein ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/metabolism ; Epithelial-Mesenchymal Transition ; *Macular Degeneration/metabolism ; Fibrosis ; RNA, Small Interfering/metabolism ; *Sulfonamides ; },
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation of fibrotic scar in the macular region. The pathogenesis of subretinal fibrosis in nAMD involves the process of epithelial-mesenchymal transition (EMT) occurring in retinal pigment epithelium (RPE). Here, we aim to investigate the underlying mechanisms involved in the Wnt signaling during the EMT of RPE cells and in the pathological process of subretinal fibrosis secondary to nAMD.<br><br>METHODS: In vivo, the induction of subretinal fibrosis was performed in male C57BL/6J mice through laser photocoagulation. Either FH535 (a &#x3b2;-catenin inhibitor) or Box5 (a Wnt5a inhibitor) was intravitreally administered on the same day or 14&#xa0;days following laser induction. The RPE-Bruch's membrane-choriocapillaris complex (RBCC) tissues were collected and subjected to Western blot analysis and immunofluorescence to examine fibrovascular and Wnt-related markers. In vitro, transforming growth factor beta 1 (TGF&#x3b2;1)-treated ARPE-19 cells were co-incubated with or without FH535, Foxy-5 (a Wnt5a-mimicking peptide), Box5, or Wnt5a shRNA, respectively. The changes in EMT- and Wnt-related signaling molecules, as well as cell functions were assessed using qRT-PCR, nuclear-cytoplasmic fractionation assay, Western blot, immunofluorescence, scratch assay or transwell migration assay. The cell viability of ARPE-19 cells was determined using Cell Counting Kit (CCK)-8.<br><br>RESULTS: The in vivo analysis demonstrated Wnt5a/ROR1, but not Wnt3a, was upregulated in the RBCCs of the laser-induced CNV mice compared to the normal control group. Intravitreal injection of FH535 effectively reduced Wnt5a protein expression. Both FH535 and Box5 effectively attenuated subretinal fibrosis and EMT, as well as the activation of &#x3b2;-catenin in laser-induced CNV mice, as evidenced by the significant reduction in areas positive for fibronectin, alpha-smooth muscle actin (&#x3b1;-SMA), collagen I, and active &#x3b2;-catenin labeling. In vitro, Wnt5a/ROR1, active &#x3b2;-catenin, and some other Wnt signaling molecules were upregulated in the TGF&#x3b2;1-induced EMT cell model using ARPE-19 cells. Co-treatment with FH535, Box5, or Wnt5a shRNA markedly suppressed the activation of Wnt5a, nuclear translocation of active &#x3b2;-catenin, as well as the EMT in TGF&#x3b2;1-treated ARPE-19 cells. Conversely, treatment with Foxy-5 independently resulted in the activation of abovementioned molecules and subsequent induction of EMT in ARPE-19 cells.<br><br>CONCLUSIONS: Our study reveals a reciprocal activation between Wnt5a and &#x3b2;-catenin to mediate EMT as a pivotal driver of subretinal fibrosis in nAMD. This positive feedback loop provides valuable insights into potential therapeutic strategies to treat subretinal fibrosis in nAMD patients.},
}
@article {pmid38530568,
year = {2024},
author = {Ghosh, AK and Nikumbh, US and Shukla, CK and Laul, RS and Dixit, A and Mahapatra, SK and Nayak, S and Shah, UM and Parwal, S and Venkatapathy, N and Radhakrishnan, N and Kelgaonkar, A and Saxena, S and Mishra, D and Dave, VP and Khan, P and Saswade, MR and Shantilal, MS and Ramasamy, K and Sreekanta, S and Rajurkar, M and Doshi, M and Behera, S and Patel, P and Dhawan, S and Lakhwani, L},
title = {Efficacy, Safety and Immunogenicity of Sun's Ranibizumab Biosimilar in Neovascular Age-Related Macular Degeneration: A Phase 3, Double-Blind Comparative Study.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {5},
pages = {1369-1382},
pmid = {38530568},
issn = {2193-8245},
abstract = {INTRODUCTION: The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun's ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD&#x2009;&#x2265;&#x2009;50&#xa0;years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5&#xa0;mg (0.05&#xa0;mL) intravitreal injection of either Sun's ranibizumab or reference ranibizumab in the study eye every 4&#xa0;weeks until week 16 (total of four doses).<br><br>RESULTS: Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week&#xa0;16 (99% of patients in Sun's ranibizumab and 100% in reference ranibizumab; p&#x2009;>&#x2009;0.9999), with the proportional difference (90% confidence interval) at -1% (-2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun's ranibizumab group and 37% of the reference ranibizumab group (p&#x2009;=&#x2009;0.4267). The mean increase in BCVA was 15.7 letters in Sun's ranibizumab group and 14.6 letters in the reference ranibizumab group (p&#x2009;<&#x2009;0.001 within both groups and p&#x2009;=&#x2009;0.5275 between groups). The mean change in central macular thickness was comparable between groups (p&#x2009;=&#x2009;0.7946). Anti-ranibizumab antibodies were found in one patient of the reference ranibizumab group, while neutralising antibodies were not found in any patients. Both products were well tolerated.<br><br>CONCLUSION: Sun's ranibizumab biosimilar is found to be therapeutically equivalent to reference ranibizumab in patients with nAMD. There were no additional safety or immunogenicity concerns.<br><br>TRIAL REGISTRATION: CTRI/2020/09/027629, registered on 07 September 2020.},
}
@article {pmid38528623,
year = {2024},
author = {Kananen, F and Kaprio, J and Immonen, I},
title = {Age-related macular degeneration discordance in monozygotic twin pairs.},
journal = {Acta ophthalmologica},
volume = {102},
number = {6},
pages = {714-719},
doi = {10.1111/aos.16671},
pmid = {38528623},
issn = {1755-3768},
support = {#352792//Academy of Finland Centre of Excellence in Complex Disease Genetics/ ; //Silm&#xe4;s&#xe4;&#xe4;ti&#xf6;/ ; },
mesh = {Humans ; *Twins, Monozygotic/genetics ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Bruch Membrane/pathology ; *Macular Degeneration/diagnosis/genetics ; *Diseases in Twins/diagnosis/genetics ; Aged, 80 and over ; Finland/epidemiology ; Middle Aged ; },
abstract = {PURPOSE: To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs.<br><br>METHODS: In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35-degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age-Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE-BrM complex volume was calculated with the Orion&#x2122; software. The worse eye according to AREDS classification was used for the analysis.<br><br>RESULTS: Twenty-nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2-4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3-4) versus the other being unaffected (AREDS 1). The within-pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418-0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE-BrM complex volume. RPE-BrM complex volume showed a within twin pair correlation, r&#x2009;=&#x2009;0.430 (95% confidence interval 0.172-0.688, p&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: A substantial proportion of monozygotic twin pairs are discordant with regard to age-related macular degeneration phenotype. RPE-BrM complex volume associated with age and intermediate and late AMD.},
}
@article {pmid38528525,
year = {2024},
author = {Abcouwer, SF and Miglioranza Scavuzzi, B and Kish, PE and Kong, D and Shanmugam, S and Le, XA and Yao, J and Hager, H and Zacks, DN},
title = {The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment.},
journal = {Journal of neuroinflammation},
volume = {21},
number = {1},
pages = {74},
pmid = {38528525},
issn = {1742-2094},
support = {T32 AR007080/AR/NIAMS NIH HHS/United States ; T32AR07080/AR/NIAMS NIH HHS/United States ; P30EY007003/EY/NEI NIH HHS/United States ; S10 OD028612/OD/NIH HHS/United States ; R01 EY020823/EY/NEI NIH HHS/United States ; P30 EY007003/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; Humans ; Retinal Pigment Epithelium/metabolism ; *Retinal Detachment/metabolism ; Retina/metabolism ; *Macular Degeneration/metabolism ; Phagocytosis/genetics ; Bone Morphogenetic Protein Receptors/metabolism ; },
abstract = {The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional and metabolic relationships between these layers. Although the retinal response to RD is highly studied, little is known about how the RPE responds to loss of this interaction. RNA sequencing (RNA-Seq) was used to compare normal and detached RPE in the C57BL6/J mouse. The naïve mouse RPE transcriptome was compared to previously published RPE signature gene lists and from the union of these 14 genes (Bmp4, Crim1, Degs1, Gja1, Itgav, Mfap3l, Pdpn, Ptgds, Rbp1, Rnf13, Rpe65, Slc4a2, Sulf1 and Ttr) representing a core signature gene set applicable across rodent and human RPE was derived. Gene ontology enrichment analysis (GOEA) of the mouse RPE transcriptome identified expected RPE features and functions, such as pigmentation, phagocytosis, lysosomal and proteasomal degradation of proteins, and barrier function. Differentially expressed genes (DEG) at 1 and 7 days post retinal detachment (dprd) were defined as mRNA with a significant (padj≤0.05) fold change (FC) of 0.67 ≥ FC ≥ 1.5 in detached versus naïve RPE. The RPE transcriptome exhibited dramatic changes at 1 dprd, with 2297 DEG identified. The KEGG pathways and biological process GO groups related to innate immune responses were significantly enriched. Lipocalin 2 (Lcn2) and several chemokines were upregulated, while numerous genes related to RPE functions, such as pigment synthesis, visual cycle, phagocytosis, and tight junctions were downregulated at 1 dprd. The response was largely transient, with only 18 significant DEG identified at 7 dprd, including upregulation of complement gene C4b. Validation studies confirmed RNA-Seq results. Thus, the RPE quickly downregulates cell-specific functions and mounts an innate immune defense response following RD. Our data demonstrate that the RPE contributes to the inflammatory response to RD and may play a role in attraction of immune cells to the subretinal space.},
}
@article {pmid38526161,
year = {2024},
author = {Sezgin, E and Schneider, MF and Hunt, PW and Beck-Engeser, G and Ambayac, GC and Jabs, DA},
title = {Genetic factors associated with age-related macular degeneration modulating plasma inflammatory biomarker levels in patients with AIDS.},
journal = {Ophthalmic genetics},
volume = {45},
number = {4},
pages = {337-342},
pmid = {38526161},
issn = {1744-5094},
support = {R01 EY025093/EY/NEI NIH HHS/United States ; },
mesh = {Female ; Humans ; Male ; Middle Aged ; *Acquired Immunodeficiency Syndrome/blood/genetics ; *Biomarkers/blood ; C-Reactive Protein/metabolism/analysis/genetics ; *Chemokine CX3CL1/blood/genetics ; Complement Factor H/genetics ; CX3C Chemokine Receptor 1/genetics ; Genotype ; Interleukin-18/blood/genetics ; Lipopolysaccharide Receptors/blood/genetics ; *Macular Degeneration/blood/genetics ; Polymorphism, Single Nucleotide ; Receptors, Tumor Necrosis Factor, Type II/blood/genetics ; Risk Factors ; Black or African American/genetics ; White/genetics ; },
abstract = {INTRODUCTION: Patients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS.<br><br>MATERIALS AND METHODS: Cryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C&#x2009;&#xd7;&#x2009;3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C&#x2009;&#xd7;&#x2009;3motif chemokine receptor 1 (CX3CR1).<br><br>RESULTS: In Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels.<br><br>CONCLUSIONS: Genetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.},
}
@article {pmid38524531,
year = {2024},
author = {Tu, Y and Guo, Y and Sun, H and Zhang, Y and Wang, Q and Xu, Y and Xie, L and Zhu, M},
title = {Tocilizumab attenuates choroidal neovascularization by regulating macrophage polarization through the IL-6R/STAT3/VEGF pathway.},
journal = {Heliyon},
volume = {10},
number = {6},
pages = {e27893},
pmid = {38524531},
issn = {2405-8440},
abstract = {Globally, age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment. Up to 80% of severe vision loss is caused by AMD, which is characterized by the development of choroidal neovascularization (CNV). Uncertainty exists regarding the precise pathophysiological mechanisms of CNV. It has been suggested that the interleukin (IL) IL-6/IL-6R signaling pathway is crucial in the progression of CNV. Tocilizumab (TCZ), a monoclonal antibody, binds to soluble and membrane-bound IL-6R and competitively inhibits IL-6 downstream signaling. Previous research has demonstrated that TCZ promotes several roles related to inflammation and neovascularization. However, the effects of TCZ on CNV and the underlying mechanism are still unknown. This study found that TCZ administration decreased the area and leakage of CNV lesions in the mice model of laser-induced CNV. Additionally, results demonstrated that TCZ promotes the expression of iNOS, CCL-3, CCL-5, TNF-α and inhibits the expression of Arg-1, IL-10, YM-1 and CD206. Furthermore, TCZ treatment inhibited the signal transducer and activator of transcription (STAT) STAT3/vascular endothelial growth factor (VEGF) pathway, which was activated after CNV formation. Colivelin, a STAT3 agonist, reversed the inhibitory effects of TCZ on CNV formation and macrophage polarization. In a mouse model of laser-induced CNV, our findings demonstrated that TCZ attenuated CNV formation and inhibited the leakage of CNV lesions by regulating macrophage polarization via inhibiting the STAT3/VEGF axis. TCZ is the potential therapeutic strategy for CNV.},
}
@article {pmid38524380,
year = {2024},
author = {Lin, JB and Santeford, A and Usmani, D and Shah, AV and Ruzycki, PA and Apte, RS},
title = {Cell-specific Systemic Immune Signatures Associated with Treatment Burden in Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {2},
pages = {100410},
pmid = {38524380},
issn = {2666-9145},
abstract = {PURPOSE: Choroidal neovascularization (CNV) accounts for the majority of severe vision loss in neovascular age-related macular degeneration (AMD). Despite therapies that target VEGF, patients are often under-responsive, require frequent eye injections to control disease, and eventually lose some vision despite chronic therapy implicating a multifactorial etiology in treatment response. Genetic studies implicate systemic immunity in AMD and systemic immune cells accumulate within CNV lesions, yet a role for these cells in anti-VEGF response remains undetermined. The purpose of this study was to identify transcriptional signatures of circulating immune cells that are associated with high anti-VEGF treatment burden.<br><br>DESIGN: Experimental pilot study.<br><br>PARTICIPANTS: Patients with neovascular AMD seen at Washington University School of Medicine in St. Louis and BJC Health System.<br><br>METHODS: We profiled by single cell RNA sequencing the peripheral blood mononuclear cells of 27 treatment-experienced patients with wet AMD. We stratified this cohort into 2 groups with low and high treatment burden (&#x2264;&#xa0;5 or &#x2265; 6 injections in the past 12 months, respectively).<br><br>MAIN OUTCOME MEASURES: Identification of immune cells associated with high treatment burden.<br><br>RESULTS: Gene expression signature of CD16+ monocytes may be associated with high treatment burden.<br><br>CONCLUSIONS: These studies delineate potential signatures of circulating immune cells that may be associated with high treatment burden in neovascular AMD, potentially informing the development of diagnostic predictors of anti-VEGF response and new precision medicine-based approaches to complement anti-VEGF therapies.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38522916,
year = {2024},
author = {Ferrara, N},
title = {Molecular Basis of Angiogenesis and its Application.},
journal = {The Keio journal of medicine},
volume = {73},
number = {1},
pages = {12},
doi = {10.2302/kjm.ABSTRACT_73_1-1},
pmid = {38522916},
issn = {1880-1293},
mesh = {Animals ; Mice ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; Vascular Endothelial Growth Factor A/genetics ; Antibodies, Monoclonal, Humanized/therapeutic use ; Angiogenesis ; *Wet Macular Degeneration/drug therapy ; Visual Acuity ; Neovascularization, Pathologic/drug therapy/genetics/metabolism ; *Neoplasms ; },
abstract = {Angiogenesis, the development of new blood vessels, is a fundamental physiological process. In addition, angiogenesis plays a key role in the pathogenesis of several disorders, including cancer and eye disorders such as diabetic retinopathy and age-related macular degeneration (AMD). However, identifying the regulators of angiogenesis proved challenging. Numerous factors that stimulated angiogenesis in various bioassays were identified, but their pathophysiological role remained unclear. In 1989, we reported the isolation and cloning of vascular endothelial growth factor (VEGF, VEGF-A) as an endothelial cell-specific mitogen and angiogenic factor. The tyrosine kinases Flt-1 (VEGFR-1) and KDR (VEGFR-2) were subsequently identified as VEGF receptors. Loss of a single vegfa allele results in defective vascularization and embryonic lethality in mice, emphasizing the essential role of VEGF in the development of blood vessels. Subsequently, we reported that anti-VEGF monoclonal antibodies block growth and neovascularization in tumor models. These findings paved the way for the clinical development of a humanized anti-VEGF antibody and other VEGF inhibitors for cancer therapy. To date, several VEGF inhibitors represent standard of care for colorectal cancer and other difficult to treat malignancies. VEGF is also implicated in intraocular neovascularization associated with retinal disorders as well as neovascular AMD. Our group developed a humanized anti-VEGF-A antibody fragment (ranibizumab) for the treatment of wet AMD. Ranibizumab not only maintained but also improved visual acuity and has been approved worldwide for the treatment of wet AMD and other neovascular disorders. Other VEGF inhibitors, including bevacizumab and aflibercept, have also resulted in significant clinical benefits. Today anti-VEGF drugs represent the most effective therapy for intraocular neovascularization. Current research addresses the need to reduce the frequency of intravitreal injections as well the identification of additional pro-angiogenic pathways that could result in improving therapeutic outcomes.},
}
@article {pmid38522635,
year = {2024},
author = {Qarawani, A and Naaman, E and Ben-Zvi Elimelech, R and Harel, M and Itzkovich, C and Safuri, S and Dahan, N and Henkin, J and Zayit-Soudry, S},
title = {PEDF-derived peptide protects against Amyloid-β toxicity in vitro and prevents retinal dysfunction in rats.},
journal = {Experimental eye research},
volume = {242},
number = {},
pages = {109861},
doi = {10.1016/j.exer.2024.109861},
pmid = {38522635},
issn = {1096-0007},
mesh = {Animals ; *Serpins/metabolism ; *Eye Proteins/metabolism ; *Nerve Growth Factors/metabolism ; Rats ; *Amyloid beta-Peptides/toxicity/metabolism ; *Electroretinography ; Retinal Pigment Epithelium/drug effects/metabolism ; Peptide Fragments/toxicity ; Disease Models, Animal ; Receptors, Laminin/metabolism ; Male ; Retina/drug effects/metabolism ; Humans ; Intravitreal Injections ; Blotting, Western ; Retinal Diseases/prevention &amp; control/metabolism/chemically induced ; Cells, Cultured ; },
abstract = {Amyloid-beta (Aβ), a family of aggregation-prone and neurotoxic peptides, has been implicated in the pathophysiology of age-related macular degeneration (AMD). We have previously shown that oligomeric and fibrillar species of Aβ42 exerted retinal toxicity in rats, but while the consequences of exposure to amyloid were related to intracellular effects, the mechanism of Aβ42 internalization in the retina is not well characterized. In the brain, the 67 kDa laminin receptor (67LR) participates in Aβ-related neuronal cell death. A short peptide derived from pigment epithelium-derived factor (PEDF), formerly designated PEDF-335, was found to mitigate experimental models of ischemic retinopathy via targeting of 67LR. In the present study, we hypothesized that 67LR mediates the uptake of pathogenic Aβ42 assemblies in the retina, and that targeting of this receptor by PEDF-335 may limit the internalization of Aβ, thereby ameliorating its retinotoxicity. To test this assumption ARPE-19 cells in culture were incubated with PEDF-335 before treatment with fibrillar or oligomeric structures of Aβ42. Immunostaining confirmed that PEDF-335 treatment substantially prevented amyloid internalization into ARPE-19 cells and maintained their viability in the presence of toxic oligomeric and fibrillar Aβ42 entities in vitro. FRET competition assay was performed and confirmed the binding of PEDF-335 to 67LR in RPE-like cells. Wild-type rats were treated with intravitreal PEDF-335 in the experimental eye 2 days prior to administration of retinotoxic Aβ42 oligomers or fibrils to both eyes. Retinal function was assessed by electroretinography through 6 weeks post injection. The ERG responses in rats treated with oligomeric or fibrillar Aβ42 assemblies were near-normal in eyes previously treated with intravitreal PEDF-335, whereas those measured in the control eyes treated with injection of the Aβ42 assemblies alone showed pathologic attenuation of the retinal function through 6 weeks. The retinal presence of 67LR was determined ex vivo by immunostaining and western blotting. Retinal staining demonstrated the constitutional expression of 67LR mainly in the retinal nuclear layers. In the presence of Aβ42, the levels of 67LR were increased, although its retinal distribution remained largely unaltered. In contrast, no apparent differences in the retinal expression level of 67LR were noted following exposure to PEDF-335 alone, and its pattern of localization in the retina remained similarly concentrated primarily in the inner and outer nuclear layers. In summary, we found that PEDF-335 confers protection against Aβ42-mediated retinal toxicity, with significant effects noted in cells as well as in vivo in rats. The effects of PEDF-335 in the retina are potentially mediated via binding to 67LR and by at least partial inhibition of Aβ42 internalization. These results suggest that PEDF-335 may merit further consideration in the development of targeted inhibition of amyloid-related toxicity in the retina. More broadly, our observations provide evidence on the importance of extracellular versus intracellular Aβ42 in the retina and suggest concepts on the molecular mechanism of Aβ retinal pathogenicity.},
}
@article {pmid38521951,
year = {2024},
author = {Gandhi, P and Wang, Y and Li, G and Wang, S},
title = {The role of long noncoding RNAs in ocular angiogenesis and vascular oculopathy.},
journal = {Cell &amp; bioscience},
volume = {14},
number = {1},
pages = {39},
pmid = {38521951},
issn = {2045-3701},
support = {R01 EY035805/EY/NEI NIH HHS/United States ; R01 EY034571/EY/NEI NIH HHS/United States ; EY026069/EY/NEI NIH HHS/United States ; EY021862/EY/NEI NIH HHS/United States ; EY034571/EY/NEI NIH HHS/United States ; },
abstract = {Long noncoding RNAs (lncRNAs) are RNA transcripts over 200 nucleotides in length that do not code for proteins. Initially considered a genomic mystery, an increasing number of lncRNAs have been shown to have vital roles in physiological and pathological conditions by regulating gene expression through diverse mechanisms depending on their subcellular localization. Dysregulated angiogenesis is responsible for various vascular oculopathies, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and corneal neovascularization. While anti-VEGF treatment is available, it is not curative, and long-term outcomes are suboptimal, and some patients are unresponsive. To better understand these diseases, researchers have investigated the role of lncRNAs in regulating angiogenesis and models of vascular oculopathies. This review summarizes recent research on lncRNAs in ocular angiogenesis, including the pro-angiogenic lncRNAs ANRIL, HOTAIR, HOTTIP, H19, IPW, MALAT1, MIAT, NEAT1, and TUG1, the anti-angiogenic lncRNAs MEG3 and PKNY, and the human/primate specific lncRNAs lncEGFL7OS, discussing their functions and mechanisms of action in vascular oculopathies.},
}
@article {pmid38521423,
year = {2024},
author = {Bressler, NM and Kaiser, PK and Do, DV and Nguyen, QD and Park, KH and Woo, SJ and Sagong, M and Bradvica, M and Kim, MY and Kim, S and Sadda, SR},
title = {Biosimilars of anti-vascular endothelial growth factor for ophthalmic diseases: A review.},
journal = {Survey of ophthalmology},
volume = {69},
number = {4},
pages = {521-538},
doi = {10.1016/j.survophthal.2024.03.009},
pmid = {38521423},
issn = {1879-3304},
mesh = {Humans ; *Biosimilar Pharmaceuticals/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; Eye Diseases/drug therapy ; Retinal Diseases/drug therapy ; },
abstract = {The development of intravitreally injected biologic medicines (biologics) acting against vascular endothelial growth factor (VEGF) substantially improved the clinical outcomes of patients with common VEGF-driven retinal diseases. The relatively high cost of branded agents, however, represents a financial burden for most healthcare systems and patients, likely resulting in impaired access to treatment and poorer clinical outcomes for some patients. Biosimilar medicines (biosimilars) are clinically equivalent, potentially economic alternatives to reference products. Biosimilars approved by leading health authorities have been demonstrated to be similar to the reference product in a comprehensive comparability exercise, generating the totality of evidence necessary to support analytical, pre-clinical, and clinical biosimilarity. Anti-VEGF biosimilars have been entering the field of ophthalmology in the US since 2022. We review regulatory and scientific concepts of biosimilars, the biosimilar development landscape in ophthalmology, with a specific focus on anti-VEGF biosimilars, and discuss opportunities and challenges facing the uptake of biosimilars.},
}
@article {pmid38521386,
year = {2024},
author = {Bejarano, E and Domenech-Bendaña, A and Avila-Portillo, N and Rowan, S and Edirisinghe, S and Taylor, A},
title = {Glycative stress as a cause of macular degeneration.},
journal = {Progress in retinal and eye research},
volume = {101},
number = {},
pages = {101260},
pmid = {38521386},
issn = {1873-1635},
support = {R01 EY021212/EY/NEI NIH HHS/United States ; R01 EY026979/EY/NEI NIH HHS/United States ; R01 EY028559/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/etiology ; Animals ; *Glycation End Products, Advanced/metabolism ; Glycemic Index/physiology ; Blood Glucose/metabolism ; Dietary Carbohydrates/adverse effects ; },
abstract = {People are living longer and rates of age-related diseases such as age-related macular degeneration (AMD) are accelerating, placing enormous burdens on patients and health care systems. The quality of carbohydrate foods consumed by an individual impacts health. The glycemic index (GI) is a kinetic measure of the rate at which glucose arrives in the blood stream after consuming various carbohydrates. Consuming diets that favor slowly digested carbohydrates releases sugar into the bloodstream gradually after consuming a meal (low glycemic index). This is associated with reduced risk for major age-related diseases including AMD, cardiovascular disease, and diabetes. In comparison, consuming the same amounts of different carbohydrates in higher GI diets, releases glucose into the blood rapidly, causing glycative stress as well as accumulation of advanced glycation end products (AGEs). Such AGEs are cytotoxic by virtue of their forming abnormal proteins and protein aggregates, as well as inhibiting proteolytic and other protective pathways that might otherwise selectively recognize and remove toxic species. Using in vitro and animal models of glycative stress, we observed that consuming higher GI diets perturbs metabolism and the microbiome, resulting in a shift to more lipid-rich metabolomic profiles. Interactions between aging, diet, eye phenotypes and physiology were observed. A large body of laboratory animal and human clinical epidemiologic data indicates that consuming lower GI diets, or lower glycemia diets, is protective against features of early AMD (AMDf) in mice and AMD prevalence or AMD progression in humans. Drugs may be optimized to diminish the ravages of higher glycemic diets. Human trials are indicated to determine if AMD progression can be retarded using lower GI diets. Here we summarized the current knowledge regarding the pathological role of glycative stress in retinal dysfunction and how dietary strategies might diminish retinal disease.},
}
@article {pmid38520643,
year = {2024},
author = {Zarbin, MA and MacCumber, MW and Karcher, H and Adiguzel, E and Mayhook, A and LaPrise, A and Bilano, VL and Igwe, F and Ip, MS and Wykoff, CC},
title = {Real-World Safety Outcomes with Brolucizumab in Neovascular Age-Related Macular Degeneration: Findings from the IRIS® Registry.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {5},
pages = {1357-1368},
pmid = {38520643},
issn = {2193-8245},
abstract = {INTRODUCTION: To assess real-world safety outcomes for adults with neovascular age-related macular degeneration (nAMD) treated with brolucizumab from the US-based IRIS® (Intelligent Research in Sight) Registry.<br><br>METHODS: In this retrospective study, 18,312 eyes (15,998 patients) treated with&#x2009;&#x2265;&#x2009;1 intravitreal brolucizumab injections between 8 October 2019 (US launch date for brolucizumab) and 7 October 2021 were followed up for&#x2009;&#x2264;&#x2009;2&#xa0;years after first injection (index date). The study assessed the predefined incident ocular adverse events of intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RO).<br><br>RESULTS: Overall, 614/18,312 eyes (3.4%) experienced any IOI, RV, and/or RO event. Median (interquartile range [IQR]) time to an event was 84 (42-167) days; 77.4% of events (475/614) occurred within 6&#xa0;months after index date. Median (IQR) number of brolucizumab injections before an event was 2 (1-4). For eyes with an adverse event and visual acuity (VA) data (n&#x2009;=&#x2009;406), median (IQR) change in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from pre-event VA was 0 (-&#x2009;7 to&#x2009;+ 5) at the 6-month follow-up; 50 eyes (12.3%) had a VA loss of&#x2009;10 or more ETDRS letters. Risk of an event (hazard ratio [95% confidence interval]) was decreased in eyes from male patients (0.61 [0.53-0.71]), from older patients (0.83 [0.76-0.90]), from treatment-naive patients (0.51 [0.38-0.69]), and from patients who started brolucizumab in the second year after launch (0.68 [0.53-0.86] vs. first year).<br><br>CONCLUSION: In this large real-world brolucizumab safety study, 3.4% of eyes experienced an IOI, RV, and/or RO event. Among eyes that experienced an adverse event for which VA data were available, median ETDRS vision change was 0 letters (IQR -&#x2009;7 to&#x2009;+&#xa0;5).},
}
@article {pmid38519026,
year = {2024},
author = {Cai, CX and Nishimura, A and Bowring, MG and Westlund, E and Tran, D and Ng, JH and Nagy, P and Cook, M and McLeggon, JA and DuVall, SL and Matheny, ME and Golozar, A and Ostropolets, A and Minty, E and Desai, P and Bu, F and Toy, B and Hribar, M and Falconer, T and Zhang, L and Lawrence-Archer, L and Boland, MV and Goetz, K and Hall, N and Shoaibi, A and Reps, J and Sena, AG and Blacketer, C and Swerdel, J and Jhaveri, KD and Lee, E and Gilbert, Z and Zeger, SL and Crews, DC and Suchard, MA and Hripcsak, G and Ryan, PB},
title = {Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {8},
pages = {733-743},
pmid = {38519026},
issn = {2468-6530},
support = {U24 HD113136/HD/NICHD NIH HHS/United States ; R01 LM006910/LM/NLM NIH HHS/United States ; F30 HL168842/HL/NHLBI NIH HHS/United States ; K23 EY032985/EY/NEI NIH HHS/United States ; R01 LM013426/LM/NLM NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; K23 DK132459/DK/NIDDK NIH HHS/United States ; K23 EY033440/EY/NEI NIH HHS/United States ; R01 AG068002/AG/NIA NIH HHS/United States ; K24 HL148181/HL/NHLBI NIH HHS/United States ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Bevacizumab/administration &amp; dosage/adverse effects ; Blindness/epidemiology/chemically induced/prevention &amp; control/diagnosis/etiology ; Diabetic Retinopathy/drug therapy/epidemiology/diagnosis/complications ; Follow-Up Studies ; Incidence ; Intravitreal Injections ; Macular Edema/drug therapy/epidemiology/diagnosis ; *Ranibizumab/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; *Renal Insufficiency/epidemiology/complications/chemically induced ; Retinal Vein Occlusion/drug therapy/diagnosis/complications/epidemiology ; Retrospective Studies ; Risk Factors ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {PURPOSE: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab.<br><br>DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network.<br><br>SUBJECTS: Subjects aged &#x2265; 18 years with &#x2265; 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion).<br><br>METHODS: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate.<br><br>MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure.<br><br>RESULTS: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P&#xa0;= 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P&#xa0;= 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P&#xa0;= 0.60).<br><br>CONCLUSIONS: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38517913,
year = {2024},
author = {Yang, J and Wang, G and Xiao, X and Bao, M and Tian, G},
title = {Explainable ensemble learning method for OCT detection with transfer learning.},
journal = {PloS one},
volume = {19},
number = {3},
pages = {e0296175},
pmid = {38517913},
issn = {1932-6203},
mesh = {Humans ; *Macular Edema/diagnostic imaging ; *Diabetic Retinopathy/diagnostic imaging ; Tomography, Optical Coherence/methods ; Artificial Intelligence ; *Deep Learning ; },
abstract = {The accuracy and interpretability of artificial intelligence (AI) are crucial for the advancement of optical coherence tomography (OCT) image detection, as it can greatly reduce the manual labor required by clinicians. By prioritizing these aspects during development and application, we can make significant progress towards streamlining the clinical workflow. In this paper, we propose an explainable ensemble approach that utilizes transfer learning to detect fundus lesion diseases through OCT imaging. Our study utilized a publicly available OCT dataset consisting of normal subjects, patients with dry age-related macular degeneration (AMD), and patients with diabetic macular edema (DME), each with 15 samples. The impact of pre-trained weights on the performance of individual networks was first compared, and then these networks were ensemble using majority soft polling. Finally, the features learned by the networks were visualized using Grad-CAM and CAM. The use of pre-trained ImageNet weights improved the performance from 68.17% to 92.89%. The ensemble model consisting of the three CNN models with pre-trained parameters loaded performed best, correctly distinguishing between AMD patients, DME patients and normal subjects 100% of the time. Visualization results showed that Grad-CAM could display the lesion area more accurately. It is demonstrated that the proposed approach could have good performance of both accuracy and interpretability in retinal OCT image detection.},
}
@article {pmid38517446,
year = {2024},
author = {Sangani, P and Temple, S and Bhandary, S and Narayanan, R and Johnson, E and Das, AV and Ali, MH and Takkar, B},
title = {Macular Pigment Assessment in Indian Population Using Degree of Polarization Threshold: Impact of Diet on Macular Pigment Density.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {3},
pages = {20},
pmid = {38517446},
issn = {2164-2591},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; *Macular Pigment ; Retinal Pigments ; *Macula Lutea ; Diet ; *Hypertension ; },
abstract = {PURPOSE: To determine macular pigment (MP) density scores in healthy Indians and examine correlations with demographic and lifestyle variables.<br><br>METHODS: We observed 484 Indians without an ocular pathology. Body mass index (BMI) and self-reported lifestyle factors (sunglasses usage, physical activity, and smoking) were noted. MP density was assessed as the threshold of perception of the shadow of their macular pigments on their retina using a new MP assessment tool (MP-eye). Lutein and zeaxanthin intake was assessed using a prevalidated questionnaire regionally designed for the Indian diet. Clusters of participants were created for statistical analysis based on MP-eye scores secondarily to detect any relevant effects in very low, low, medium, and high ranges of MPs.<br><br>RESULTS: Data analyzed included 235 males and 249 females with mean age of 36.1 &#xb1; 12.9 years (range, 14-72). The median MP-eye score was 6 (range, 0-10, with 10 being high). Most were non-smokers (413, 85.3%) and did not use sunglasses (438, 90.5%), and 314 (64.9%) had low physical activity. Diabetes was present in 62 participants (12.8%) and hypertension in 53 (10.9%). Advancing age (r = -0.209; P < 0.000) and BMI (r = -0.094; P = 0.038) had weak negative correlation with MP-eye scores. Hypertension was less prevalent (7/88) in the cluster with the highest median MP-eye score (P = 0.033). Dietary intake of MPs and other lifestyle factors did not correlate significantly with MP-eye score overall or when analyzed in clusters.<br><br>CONCLUSIONS: MP-eye scores of an Indian population were normally distributed. Higher age, high BMI, and presence of hypertension were weakly associated with lower MP-eye scores. The impact of diet on MPs requires further evaluation.<br><br>TRANSLATIONAL RELEVANCE: This normative regional database enables risk stratification of macular degeneration.},
}
@article {pmid38516283,
year = {2024},
author = {Sutter, D and Anderson, A and Wheatley, S and Sheth, V},
title = {Quantifying Fluid and Function in Suboptimal Responders Switched From an Anti-vascular Endothelial Growth Factor (VEGF) to Faricimab.},
journal = {Cureus},
volume = {16},
number = {3},
pages = {e56652},
pmid = {38516283},
issn = {2168-8184},
abstract = {Background Anti-vascular endothelial growth factor (VEGF) injections have been successful in reducing vision loss from neovascular age-related macular degeneration, a leading cause of blindness. Due to the high treatment burden and suboptimal responses, switching to bi-specific faricimab treatment may lead to improved outcomes. Methods This retrospective chart review evaluated if suboptimal responders to anti-VEGF injections had better outcomes when switched to faricimab. Suboptimal responders were defined as patients with a history of >3 months of injections and the presence of fluid after ≥3 injections. The primary endpoints were best-corrected visual acuity, treatment interval, and fluid levels. Visual acuity measurements and optical coherence tomography were performed before each injection. The total fluid area (TFA) was measured using MATLAB 2023a (MathWorks, Natick, MA, USA). Results Nineteen eyes were included in the analysis. After three faricimab injections, average letters increased from 54.5 to 59.0 (SD: 15.3; p<0.05), and the injection interval was extended from 7.6 to 9.3 weeks (SD: 3.9; p<0.01) after four injections. Patients also experienced anatomical retinal changes, with a reduction in the TFA to 47.3% (p<0.005) after the second injection and a reduction in pigment epithelial detachment height to 82.3% (p<0.005) after one injection. The central subfield thickness was significantly reduced after the second injection (90.6% (SD: 17.6%) p<0.05). Conclusion Switching to faricimab after a suboptimal anti-VEGF response results in improvements in visual acuity, reduced treatment burden, and reduced fluid levels.},
}
@article {pmid38512243,
year = {2024},
author = {Bikbov, MM and Gilmanshin, TR and Kazakbaeva, GM and Panda-Jonas, S and Jonas, JB},
title = {Prevalence of Myopic Maculopathy Among the Very Old: The Ural Very Old Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {3},
pages = {29},
pmid = {38512243},
issn = {1552-5783},
mesh = {Humans ; Aged, 80 and over ; Prevalence ; *Macular Degeneration/diagnosis/epidemiology ; *Retinal Diseases ; *Myopia, Degenerative/epidemiology ; Fundus Oculi ; },
abstract = {PURPOSE: To assess the prevalence of myopic macular degeneration (MMD) in very old individuals.<br><br>METHODS: The population-based Ural Very Old Study (UVOS) included 1526 (81.1%) of 1882 eligible inhabitants aged &#x2265;85 years. Assessable fundus images were available for 930 (60.9%) individuals (mean age, 88.6 &#xb1; 2.7&#xa0;years). MMD was defined by macular patchy atrophies (i.e., MMD stage 3 and 4 as defined by the Pathologic Myopia Study Group).<br><br>RESULTS: MMD prevalence was 21 of 930 (2.3%; 95% CI, 1.3-3.3), with 10 individuals (1.1%; 95% CI, 0.4-1.7) having MMD stage 3 and 11 participants (1.2%; 95% CI, 0.5-1.9) MMD stage 4 disease. Within MMD stage 3 and 4, prevalence of binocular moderate to severe vision impairment was 4 of 10 (40%; 95% CI, 31-77) and 7 of 11 (64%; 95% CI, 30-98), respectively, and the prevalence of binocular blindness was 2 of 10 (20%; 95% CI, 0-50) and 3 of 11 (27%; 95% CI, 0-59), respectively. In minor myopia (axial length, 24.0 to <24.5 mm), moderate myopia (axial length, 24.5 to <26.5 mm), and high myopia (axial length, &#x2265;26.5 mm), MMD prevalence in the right eyes was 0 of 46 eyes (0%), 3 of 40 eyes (8%; 95% CI, 0-16), and 7 of 9 (78%; 95% CI, 44-100), respectively; MMD prevalence in the left eyes was 1 in 48 eyes (2%; 95% CI, 0-6), 4 of 36 eyes (11%; 95% CI, 0-22), and 3 of 4 eyes (75%; 95% CI, 0-100), respectively. In multivariable analysis, a higher MMD prevalence (odds ratio, 8.89; 95% CI, 3.43-23.0; P < 0.001) and higher MMD stage (beta, 0.45; B, 19; 95% CI, 0.16-0.22; P < 0.001) were correlated with longer axial length but not with any other ocular or systemic parameter.<br><br>CONCLUSIONS: MMD prevalence (stages 3 and 4) in very old individuals increased 8.89-fold for each mm axial length increase, with a prevalence of &#x2265;75% in highly myopic eyes. In old age, highly myopic individuals have a high risk of eventually developing MMD with marked vision impairment.},
}
@article {pmid38510130,
year = {2024},
author = {Varner, LR and Chaya, T and Maeda, Y and Tsutsumi, R and Zhou, S and Tsujii, T and Okuzaki, D and Furukawa, T},
title = {The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases.},
journal = {iScience},
volume = {27},
number = {4},
pages = {109380},
pmid = {38510130},
issn = {2589-0042},
abstract = {Primary and secondary cone photoreceptor death in retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), leads to severe visual impairment and blindness. Although the cone photoreceptor protection in retinal degenerative diseases is crucial for maintaining vision, the underlying molecular mechanisms are unclear. Here, we found that the deubiquitinase Otud7b/Cezanne is predominantly expressed in photoreceptor cells in the retina. We analyzed Otud7b[-/-] mice, which were subjected to light-induced damage, a dry AMD model, or were mated with an RP mouse model, and observed increased cone photoreceptor degeneration. Using RNA-sequencing and bioinformatics analysis followed by a luciferase reporter assay, we found that Otud7b downregulates NF-κB activity. Furthermore, inhibition of NF-κB attenuated cone photoreceptor degeneration in the light-exposed Otud7b[-/-] retina and stress-induced neuronal cell death resulting from Otud7b deficiency. Together, our findings suggest that Otud7b protects cone photoreceptors in retinal degenerative diseases by modulating NF-κB activity.},
}
@article {pmid38508744,
year = {2024},
author = {Tomomatsu, M and Imamura, N and Izumi, H and Watanabe, M and Ikeda, M and Ide, T and Uchinomiya, S and Ojida, A and Jutanom, M and Morimoto, K and Yamada, KI},
title = {Oxidized-LDL Induces Metabolic Dysfunction in Retinal Pigment Epithelial Cells.},
journal = {Biological &amp; pharmaceutical bulletin},
volume = {47},
number = {3},
pages = {641-651},
doi = {10.1248/bpb.b23-00849},
pmid = {38508744},
issn = {1347-5215},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; *Macular Degeneration ; Lipoproteins, LDL/metabolism ; Oxidative Stress ; Epithelial Cells ; Retinal Pigments/metabolism/pharmacology ; },
abstract = {Recently, mitochondrial dysfunction has gained attention as a causative factor in the pathogenesis and progression of age-related macular degeneration (AMD). Mitochondrial damage plays a key role in metabolism and disrupts the balance of intracellular metabolic pathways, such as oxidative phosphorylation (OXPHOS) and glycolysis. In this study, we focused on oxidized low-density lipoprotein (ox-LDL), a major constituent of drusen that accumulates in the retina of patients with AMD, and investigated whether it could be a causative factor for metabolic alterations in retinal pigment epithelial (RPE) cells. We found that prolonged exposure to ox-LDL induced changes in fatty acid β-oxidation (FAO), OXPHOS, and glycolytic activity and increased the mitochondrial reactive oxygen species production in RPE cells. Notably, the effects on metabolic alterations varied with the concentration and duration of ox-LDL treatment. In addition, we addressed the limitations of using ARPE-19 cells for retinal disease research by highlighting their lower barrier function and FAO activity compared to those of induced pluripotent stem cell-derived RPE cells. Our findings can aid in the elucidation of mechanisms underlying the metabolic alterations in AMD.},
}
@article {pmid38508428,
year = {2024},
author = {Jansook, P and Loftsson, T and Stefánsson, E},
title = {Drug-like properties of tyrosine kinase inhibitors in ophthalmology: Formulation and topical availability.},
journal = {International journal of pharmaceutics},
volume = {655},
number = {},
pages = {124018},
doi = {10.1016/j.ijpharm.2024.124018},
pmid = {38508428},
issn = {1873-3476},
mesh = {Pharmaceutical Preparations ; *Tyrosine Kinase Inhibitors ; *Ophthalmology ; Vascular Endothelial Growth Factor A ; Administration, Topical ; Protein Kinase Inhibitors ; },
abstract = {Tyrosine kinase inhibitors (TKIs) can inhibit edema and neovascularization, such as in age-related macular degeneration and diabetic retinopathy. However, their topical administration in ophthalmology is limited by their toxicity and poor aqueous solubility. There are multiple types of TKIs, and each TKI has an affinity to more than one type of receptor. Studies have shown that ocular toxicity can be addressed by selecting TKIs that have a high affinity for specific vascular endothelial growth factor receptors (VEGFRs) but a low affinity for epidermal growth factor receptors (EGFRs). Drugs permeate from the aqueous tear fluid into the eye via passive diffusion. Thus, a sustained high concentration of the dissolved drug in the aqueous tear fluid is essential for a successful delivery to posterior tissues such as the retina. Unfortunately, the aqueous solubility of the TKIs that have the most favorable VEGFR/EGFR affinity ratio, that is, axitinib and cabozantinib, is well below 1 µg/mL, making their topical delivery very challenging. This is a review of the drug-like properties of TKIs that are currently being evaluated or have been evaluated as ophthalmic drugs. These properties include their solubilization, cyclodextrin complexation, and ability to permeate from the aqueous tear fluid to the posterior eye segment.},
}
@article {pmid38507599,
year = {2025},
author = {Song, MY and Kim, Y and Han, K and Kim, JH},
title = {Prevalence and Risk Factors of Age-Related Macular Degeneration in South Korea: Korea National Health and Nutrition Examination Survey.},
journal = {Ophthalmic epidemiology},
volume = {32},
number = {1},
pages = {34-43},
doi = {10.1080/09286586.2024.2321892},
pmid = {38507599},
issn = {1744-5086},
mesh = {Humans ; Republic of Korea/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Prevalence ; Risk Factors ; Aged ; Middle Aged ; *Nutrition Surveys ; Aged, 80 and over ; *Macular Degeneration/epidemiology ; Adult ; Age Distribution ; *Wet Macular Degeneration/epidemiology ; Sex Distribution ; },
abstract = {PURPOSE: To evaluate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population.<br><br>METHODS: In this cross-sectional study based on the Korea National Health and Nutrition Examination Survey (2017-2020) data 13,737 participants aged&#x2009;&#x2265;&#x2009;40&#x2009;years with assessable fundus images were included. The prevalence and risk factors of AMD were evaluated. The prevalence of early AMD, geographic atrophy (GA), and neovascular AMD were also assessed. Logistic regression analyses were used to identify risk factors.<br><br>RESULTS: The prevalence (95% confidence interval [CI]) of AMD was 13.94% (13.15-14.72). The prevalence (95% CI) of early AMD, GA, and neovascular AMD was 13.07% (12.29-13.85), 0.26% (0.17-0.35), and 0.61% (0.47-0.75), respectively. The prevalence increased with age; it was 3.61%, 11.33%, 20.31%, 31.37%, and 33.98% in participants in their 40s, 50s, 60s, 70s, and&#x2009;&#x2265;&#x2009;80&#x2009;years, respectively. In multivariate analysis, AMD was positively associated with older age (p&#x2009;<&#x2009;0.001; odds ratio [OR], 1.08; 95% CI, 1.07-1.09), male sex (p&#x2009;=&#x2009;0.014; OR, 1.27; 95% CI, 1.05-1.53), and lower degree of education (p&#x2009;<&#x2009;0.001; OR, 1.36 (for junior high school graduates); 95% CI, 1.12-1.65).<br><br>CONCLUSIONS: AMD was detected in approximately one-third of individuals aged&#x2009;&#x2265;&#x2009;70&#x2009;years, thus indicating that AMD is a common disease among older Koreans. Regular fundus examinations in populations with risk factors for AMD as well as education on methods to prevent or delay AMD progression, such as the Mediterranean diet, are necessary.},
}
@article {pmid38507191,
year = {2024},
author = {Boon, J and Rojas-Carabali, W and Asad, Y and Lim, JTY and Rajagopalan, R and Agrawal, R},
title = {Evaluation of a Digital Amsler Grid (PocDoc) for Macular Disease Screening: A Comparative Analysis with the Conventional Method.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {5},
pages = {1289-1301},
pmid = {38507191},
issn = {2193-8245},
support = {DEC2019_I_C1_C_02//NTF_DEC2019_I_C1_C_02/ ; },
abstract = {INTRODUCTION: Macular diseases are major contributors to visual impairment and blindness worldwide. This study introduces PocDoc, a digital version of the conventional Amsler grid, aimed at enhancing the screening and monitoring of macular diseases. We conducted a comprehensive evaluation to compare the effectiveness of PocDoc against the conventional method.<br><br>METHODS: Our comparative analysis involved two distinct phases. Initially, we assessed the capability of both PocDoc and the conventional method in detecting central visual field abnormalities. This phase included a cohort of 72 healthy and 155 eyes affected by various conditions such as age-related macular degeneration (AMD), uveitis, polypoidal choroidal vasculopathy (PCV), and macular telangiectasia. We primarily focused on the area of compromise and observed the correlation between the results obtained from both methods, measuring their concordance using a correlation coefficient. In the second phase, we evaluated the accuracy of both methods in diagnosing AMD. This involved a group of 127 eyes, including 70 healthy and 57 AMD-affected eyes. We determined the sensitivity, specificity, and overall accuracy of each method in diagnosing AMD.<br><br>RESULTS: In the initial phase, both PocDoc and the conventional Amsler grid demonstrated a high correlation in detecting central visual field defects across various macular diseases (correlation coefficient&#x2009;>&#x2009;0.9). In the second phase, focused on AMD diagnosis, PocDoc showed a sensitivity of 50%, specificity of 100%, and an overall accuracy of 78%. Comparatively, the conventional method exhibited a sensitivity of 49%, specificity of 100%, and accuracy of 77%.<br><br>CONCLUSION: PocDoc's digital Amsler grid exhibits comparable effectiveness to the conventional method in both detecting visual field abnormalities across a range of macular diseases and specifically in the diagnosis of AMD. The high correlation in results, combined with the digital advantages of PocDoc, such as ease of use and potential for telemedicine applications, suggests its viability as a valuable tool in the screening and monitoring of macular diseases.},
}
@article {pmid38507046,
year = {2024},
author = {Honda, S and Misawa, N and Sato, Y and Oikawa, D and Tokunaga, F},
title = {The hypothetical molecular mechanism of the ethnic variations in the manifestation of age-related macular degeneration; focuses on the functions of the most significant susceptibility genes.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {9},
pages = {2799-2811},
pmid = {38507046},
issn = {1435-702X},
support = {22K09773//Ministry of Education, Culture, Sports, Science and Technology/ ; },
mesh = {Humans ; Asian People/genetics ; Complement Factor H/genetics ; Ethnicity/genetics ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; High-Temperature Requirement A Serine Peptidase 1/genetics ; *Macular Degeneration/genetics/ethnology/diagnosis ; Phenotype ; Polymorphism, Single Nucleotide ; Proteins/genetics ; White People/genetics ; },
abstract = {Age-related macular degeneration (AMD) is the leading sight-threatening disease in developed countries. On the other hand, recent studies indicated an ethnic variation in the phenotype of AMD. For example, several reports demonstrated that the incidence of drusen in AMD patients is less in Asians compared to Caucasians though the reason has not been clarified yet. In the last decades, several genome association studies have disclosed many susceptible genes of AMD and revealed that the association strength of some genes was different among races and AMD phenotypes. In this review article, the essential findings of the clinical studies and genome association studies for the most significant genes CFH and ARMS2/HTRA1 in AMD of different races are summarized, and theoretical hypotheses about the molecular mechanisms underlying the ethnic variation in the AMD manifestation mainly focused on those genes between Caucasians and Asians are discussed.},
}
@article {pmid38504520,
year = {2024},
author = {Yusuf, IH and Burgoyne, T and Salman, A and McClements, ME and MacLaren, RE and Charbel Issa, P},
title = {Rescue of cone and rod photoreceptor function in a CDHR1-model of age-related retinal degeneration.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {32},
number = {5},
pages = {1445-1460},
pmid = {38504520},
issn = {1525-0024},
support = {MR/R000735/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Animals ; Mice ; *Disease Models, Animal ; *Retinal Rod Photoreceptor Cells/metabolism/pathology ; *Cadherin Related Proteins ; *Retinal Cone Photoreceptor Cells/metabolism/pathology ; *Cadherins/genetics/metabolism ; *Retinal Degeneration/genetics/therapy/etiology ; Humans ; *Genetic Therapy/methods ; Macular Degeneration/therapy/genetics/pathology/etiology/metabolism ; *Nerve Tissue Proteins ; },
abstract = {Age-related macular degeneration (AMD) is the most common cause of untreatable blindness in the developed world. Recently, CDHR1 has been identified as the cause of a subset of AMD that has the appearance of the "dry" form, or geographic atrophy. Biallelic variants in CDHR1-a specialized protocadherin highly expressed in cone and rod photoreceptors-result in blindness from shortened photoreceptor outer segments and progressive photoreceptor cell death. Here we demonstrate long-term morphological, ultrastructural, functional, and behavioral rescue following CDHR1 gene therapy in a relevant murine model, sustained to 23-months after injection. This represents the first demonstration of rescue of a monogenic cadherinopathy in vivo. Moreover, the durability of CDHR1 gene therapy seems to be near complete-with morphological findings of the rescued retina not obviously different from wildtype throughout the lifespan of the mouse model. A follow-on clinical trial in patients with CDHR1-associated retinal degeneration is warranted. Hypomorphic CDHR1 variants may mimic advanced dry AMD. Accurate clinical classification is now critical, as their pathogenesis and treatment are distinct.},
}
@article {pmid38499857,
year = {2024},
author = {Trinh, M and Kalloniatis, M and Khuu, SK and Nivison-Smith, L},
title = {Retinal sensitivity changes in early/intermediate AMD: a systematic review and meta-analysis of visual field testing under mesopic and scotopic lighting.},
journal = {Eye (London, England)},
volume = {38},
number = {10},
pages = {1827-1835},
pmid = {38499857},
issn = {1476-5454},
support = {1186915//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1174385//Department of Health | National Health and Medical Research Council (NHMRC)/ ; },
mesh = {Humans ; Dark Adaptation/physiology ; Lighting ; *Macular Degeneration/physiopathology/diagnosis ; *Mesopic Vision/physiology ; *Night Vision/physiology ; Retina/physiopathology ; *Visual Field Tests ; Visual Fields/physiology ; },
abstract = {Visual fields under mesopic and scotopic lighting are increasingly being used for macular functional assessment. This review evaluates its statistical significance and clinical relevance, and the optimal testing protocol for early/intermediate age-related macular degeneration (AMD). PubMed and Embase were searched from inception to 14/05/2022. All quality assessments were performed according to GRADE guidelines. The primary outcome was global mean sensitivity (MS), further meta-analysed by: AMD classification scheme, device, test pattern, mesopic/scotopic lighting, stimuli size/chromaticity, pupil dilation, testing radius (area), background luminance, adaptation time, AMD severity, reticular pseudodrusen presence, and follow-up visit. From 1489 studies screened, 42 observational study results contributed to the primary meta-analysis. Supported by moderate GRADE certainty of the evidence, global MS was significantly reduced across all devices under mesopic and scotopic lighting with large effect size (-0.9 [-1.04, -0.75] Hedge's g, P < 0.0001). The device (P < 0.01) and lighting (P < 0.05) used were the only modifiable factors affecting global MS, whereby the mesopic MP-1 and MAIA produced the largest effect sizes and exceeded test-retest variabilities. Global MS was significantly affected by AMD severity (intermediate versus early AMD; -0.58 [-0.88, -0.29] Hedge's g or -2.55 [3.62, -1.47] MAIA-dB) and at follow-up visit (versus baseline; -0.62 [-0.84, -0.41] Hedge's g or -1.61[-2.69, -0.54] MAIA-dB). Magnitudes of retinal sensitivity changes in early/intermediate AMD are clinically relevant for the MP-1 and MAIA devices under mesopic lighting within the central 10° radius. Other factors including pupil dilation and dark adaptation did not significantly affect global MS in early/intermediate AMD.},
}
@article {pmid38499856,
year = {2024},
author = {Haj Najeeb, B and Schmidt-Erfurth, U},
title = {The potential key role of choroidal non-perfusion and rod degeneration in the pathogenesis of macular neovascularization type 3.},
journal = {Eye (London, England)},
volume = {38},
number = {10},
pages = {1836-1839},
pmid = {38499856},
issn = {1476-5454},
mesh = {Humans ; *Choroid/blood supply/pathology ; Retinal Neovascularization/physiopathology/etiology ; Macular Degeneration/physiopathology ; Retinal Rod Photoreceptor Cells/physiology/pathology ; Choroidal Neovascularization/physiopathology ; },
abstract = {Macular neovascularization type 3 (MNV3) is a multifactorial disease with distinct epidemiological, clinical, pathomorphological and topographical characteristics. This review of the literature discusses the latest experimental and clinical outcomes that could explain the pathogenesis of retinal neovascularization. Although patients with MNV3 are usually older than those with MNV1 or 2, their lesions do not coexist with, precede, or follow other types in the same eye. The regional distribution of MNV3 lesions is characterized as confined to the parafoveal macula without any involvement of the rod-free foveal area. Focal outer retinal atrophy and choroidal non-perfusion are the main structural features that occur prior to the development of retinal neovascularization. Also, histological and experimental studies of MNV3 and other non-neovascular age-related macular degeneration diseases complicated with MNV3-like lesions strongly suggest rod degeneration contributes to the pathogenesis. Therefore, the retinal neovascularization in MNV3 has a different pathogenesis from the choroidal neovascularization in MNV1 and 2 and emerging evidence indicates that choroidal non-prefusion and rod degeneration play a key role in the pathogenesis of MNV3. Accordingly, we suggest a sequence of pathological events that start with choroidal non-perfusion due to advanced age followed by hypoxia of the outer retina at the parafoveal area. This induces a remarkable degeneration of rods that triggers the growth of retinal neovascularization due to the imbalance of the angiogenic factors in the outer retina.},
}
@article {pmid38499047,
year = {2024},
author = {Scheffer, M and Menting, J and Boeije, H and van Nispen, R and van Dulmen, S},
title = {Understanding healthcare communication in age-related macular degeneration care: A mixed-methods review of patients' perspectives.},
journal = {Survey of ophthalmology},
volume = {69},
number = {4},
pages = {646-660},
doi = {10.1016/j.survophthal.2024.03.002},
pmid = {38499047},
issn = {1879-3304},
mesh = {Humans ; *Macular Degeneration/therapy/psychology ; Physician-Patient Relations ; Communication ; },
abstract = {Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people aged 50 years and older. Earlier research has indicated that the communication process between patients and healthcare professionals (HCPs) leaves considerable room for improvement in AMD care. Effective communication is essential to enhance trust in the professional and understanding of the diagnosis and treatment, and decrease anxiety and stress related to illness. We review patients' experiences, needs and preferences regarding information provision, communication style of the HCP and shared decision-making. We conducted a systematic search in PubMed, Embase, PsycINFO, CINAHL and Web of Science. Study quality was assessed using standard checklists of quality measures. Our search returned 31 eligible articles. Findings indicated current deficits in information provision for people with AMD. Patients were often ill-informed regarding the chronic character of the condition, treatment duration, nutrition, and visual aids and low vision rehabilitation. Many patients were not actively involved during the decision-making process. Altogether, patients with AMD are faced with challenges in terms of patient-HCP communication. Methods of providing information and discussing possible options for care need to be further investigated and improved for this patient group.},
}
@article {pmid38498275,
year = {2024},
author = {Rangaswamy, D and Nagaraju, SP and Bhojaraja, MV and Swaminathan, SM and Prabhu, RA and Rao, IR and Shenoy, SV},
title = {Ocular and systemic vascular endothelial growth factor ligand inhibitor use and nephrotoxicity: an update.},
journal = {International urology and nephrology},
volume = {56},
number = {8},
pages = {2635-2644},
pmid = {38498275},
issn = {1573-2584},
mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors ; Kidney Diseases/chemically induced ; Bevacizumab/adverse effects/therapeutic use ; Ranibizumab/adverse effects ; Antibodies, Monoclonal, Humanized/adverse effects ; Eye Diseases/chemically induced ; Sunitinib/adverse effects ; Aptamers, Nucleotide/adverse effects ; Intravitreal Injections ; Neoplasms/drug therapy ; Signal Transduction/drug effects ; Indazoles ; Pyrimidines ; Recombinant Fusion Proteins ; Sulfonamides ; },
abstract = {Tumor growth is intricately linked to the process of angiogenesis, with a key role played by vascular endothelial growth factor (VEGF) and its associated signaling pathways. Notably, these pathways also play a pivotal "housekeeping" role in renal physiology. Over the past decade, the utilization of VEGF signaling inhibitors has seen a substantial rise in the treatment of diverse solid organ tumors, diabetic retinopathy, age-related macular degeneration, and various ocular diseases. However, this increased use of such agents has led to a higher frequency of encountering renal adverse effects in clinical practice. This review comprehensively addresses the incidence, pathophysiological mechanisms, and current evidence concerning renal adverse events associated with systemic and intravitreal antiangiogenic therapies targeting VEGF-A and its receptors (VEGFR) and their associated signaling pathways. Additionally, we briefly explore strategies for mitigating potential risks linked to the use of these agents and effectively managing various renal adverse events, including but not limited to hypertension, proteinuria, renal dysfunction, and electrolyte imbalances.},
}
@article {pmid38498232,
year = {2024},
author = {Obasanmi, G and Uppal, M and Cui, JZ and Xi, J and Ju, MJ and Song, J and To, E and Li, S and Khan, W and Cheng, D and Zhu, J and Irani, L and Samad, I and Zhu, J and Yoo, HS and Aubert, A and Stoddard, J and Neuringer, M and Granville, DJ and Matsubara, JA},
title = {Granzyme B degrades extracellular matrix and promotes inflammation and choroidal neovascularization.},
journal = {Angiogenesis},
volume = {27},
number = {3},
pages = {351-373},
pmid = {38498232},
issn = {1573-7209},
support = {P51 OD011092/OD/NIH HHS/United States ; S10 RR024585/RR/NCRR NIH HHS/United States ; S10RR024585/NH/NIH HHS/United States ; },
mesh = {*Granzymes/metabolism ; *Choroidal Neovascularization/metabolism/pathology ; Animals ; *Extracellular Matrix/metabolism/pathology ; Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; *Inflammation/pathology/metabolism ; Mice ; *Mast Cells/metabolism/pathology/enzymology ; Thrombospondin 1/metabolism/genetics ; Mice, Inbred C57BL ; Choroid/pathology/metabolism/blood supply ; Macular Degeneration/pathology/metabolism ; Mice, Knockout ; },
abstract = {Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients. Here we investigate a novel target for AMD. Granzyme B (GzmB) is a serine protease that promotes aging, chronic inflammation and vascular permeability through the degradation of the extracellular matrix (ECM) and tight junctions. Extracellular GzmB is increased in retina pigment epithelium (RPE) and mast cells in the choroid of the healthy aging outer retina. It is further increased in donor eyes exhibiting features of nAMD and CNV. Here, we show in RPE-choroidal explant cultures that exogenous GzmB degrades the RPE-choroid ECM, promotes retinal/choroidal inflammation and angiogenesis while diminishing anti-angiogenic factor, thrombospondin-1 (TSP-1). The pharmacological inhibition of either GzmB or mast-cell degranulation significantly reduces choroidal angiogenesis. In line with our in vitro data, GzmB-deficiency reduces the extent of laser-induced CNV lesions and the age-related deterioration of electroretinogram (ERG) responses in mice. These findings suggest that targeting GzmB, a serine protease with no known endogenous inhibitors, may be a potential novel therapeutic approach to suppress CNV in nAMD.},
}
@article {pmid38497512,
year = {2024},
author = {Moir, J and Hyman, MJ and Gonnah, R and Flores, A and Hariprasad, SM and Skondra, D},
title = {The Association Between Metformin Use and New-Onset ICD Coding of Geographic Atrophy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {3},
pages = {23},
pmid = {38497512},
issn = {1552-5783},
mesh = {Aged ; Humans ; Case-Control Studies ; *Diabetes Mellitus ; *Geographic Atrophy/diagnosis ; International Classification of Diseases ; *Macular Degeneration/prevention &amp; control ; Medicare ; *Metformin/therapeutic use ; United States/epidemiology ; Middle Aged ; },
abstract = {PURPOSE: Metformin has been suggested to protect against the development of age-related macular degeneration (AMD) in multiple observational studies. However, the association between metformin and geographic atrophy (GA), a debilitating subtype of AMD, has not been analyzed.<br><br>METHODS: We conducted a case-control study of patients ages 60&#xa0;years and older with new-onset International Classification of Diseases (ICD) coding of GA in the Merative MarketScan Commercial and Medicare Databases between 2017 and 2021. Cases were matched with propensity scores estimated by age, region, hypertension, and Charlson Comorbidity Index to a control without GA of the same year. Exposure to metformin was assessed for cases and controls in the year prior to their index visit. Conditional multivariable logistic regression, adjusting for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals (CIs). This study design and analysis were repeated in a sample of patients without diabetes.<br><br>RESULTS: In the full sample, we identified 10,505 cases with GA and 10,502 matched controls without GA. In total, 1149 (10.9%) cases and 1277 (12.2%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 12% (95% CI, 0.79-0.99). In the sample of patients without diabetes, we identified 7611 cases with GA and 7608 matched controls without GA. Twenty-nine (0.4%) cases and 63 (0.8%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 47% (95% CI, 0.33-0.83).<br><br>CONCLUSIONS: Metformin may hold promise as a noninvasive, alternative agent to prevent the development of GA. This finding is notable due to shortcomings in recently approved therapeutics for GA and metformin's overall ease of use and few adverse effects. Additional studies are required to explore our findings further and motivate a clinical trial.},
}
@article {pmid38496475,
year = {2024},
author = {Calanni, JS and Aranda, ML and Dieguez, HH and Dorfman, D and Schmidt, TM and Rosenstein, RE},
title = {An ethologically relevant paradigm to assess visual contrast sensitivity in rodents.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.03.05.583559},
pmid = {38496475},
issn = {2692-8205},
abstract = {In the animal kingdom, threat information is perceived mainly through vision. The subcortical visual pathway plays a critical role in the rapid processing of visual information-induced fear, and triggers a response. Looming-evoked behavior in rodents, mimicking response to aerial predators, allowed identify the neural circuitry underlying instinctive defensive behaviors; however, the influence of disk/background contrast on the looming-induced behavioral response has not been examined, either in rats or mice. We studied the influence of the dark disk/gray background contrast in the type of rat and mouse defensive behavior in the looming arena, and we showed that rat and mouse response as a function of disk/background contrast adjusted to a sigmoid-like relationship. Both sex and age biased the contrast-dependent response, which was dampened in rats submitted to retinal unilateral or bilateral ischemia. Moreover, using genetically manipulated mice, we showed that the three type of photoresponsive retinal cells (i.e., cones, rods, and intrinsically photoresponsive retinal ganglion cells (ipRGCs)), participate in the contrast-dependent response, following this hierarchy: cones ˃> rods ˃>>ipRGCs. The cone and rod involvement was confirmed using a mouse model of unilateral non-exudative age-related macular degeneration, which only damages canonical photoreceptors and significantly decreased the contrast sensitivity in the looming arena.},
}
@article {pmid38494487,
year = {2024},
author = {Tomás, RO and Campos, A and Oliveira, N and Soares, P and Sousa, JP},
title = {Preserving visual acuity: a compelling 12-year case study of controlling neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {123},
pmid = {38494487},
issn = {1471-2415},
mesh = {Humans ; Female ; Aged ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; *Macular Edema/drug therapy ; *Choroidal Neovascularization/diagnosis/drug therapy ; Visual Acuity ; },
abstract = {INTRODUCTION: In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies.<br><br>OBJECTIVE: To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining.<br><br>CASE DESCRIPTION: A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE.<br><br>RESULTS: The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE's BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16&#xa0;&#x3bc;m (276&#xa0;&#x3bc;m to 292&#xa0;&#x3bc;m) while LE's BCVA increased by 28L (35L to 63L) and CRT decreased by 369&#xa0;&#x3bc;m (680&#xa0;&#x3bc;m to 311&#xa0;&#x3bc;m), at the twelfth year.<br><br>CONCLUSIONS: Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12&#xa0;years of treatment.},
}
@article {pmid38492584,
year = {2024},
author = {Wu, H and Jin, K and Yip, CC and Koh, V and Ye, J},
title = {A systematic review of economic evaluation of artificial intelligence-based screening for eye diseases: From possibility to reality.},
journal = {Survey of ophthalmology},
volume = {69},
number = {4},
pages = {499-507},
doi = {10.1016/j.survophthal.2024.03.008},
pmid = {38492584},
issn = {1879-3304},
mesh = {Humans ; *Artificial Intelligence/economics ; *Eye Diseases/diagnosis/economics ; Ophthalmology/economics ; Cost-Benefit Analysis ; Health Care Costs ; Mass Screening/economics/methods ; },
abstract = {Artificial Intelligence (AI) has become a focus of research in the rapidly evolving field of ophthalmology. Nevertheless, there is a lack of systematic studies on the health economics of AI in this field. We examine studies from the PubMed, Google Scholar, and Web of Science databases that employed quantitative analysis, retrieved up to July 2023. Most of the studies indicate that AI leads to cost savings and improved efficiency in ophthalmology. On the other hand, some studies suggest that using AI in healthcare may raise costs for patients, especially when taking into account factors such as labor costs, infrastructure, and patient adherence. Future research should cover a wider range of ophthalmic diseases beyond common eye conditions. Moreover, conducting extensive health economic research, designed to collect data relevant to its own context, is imperative.},
}
@article {pmid38491380,
year = {2024},
author = {Crincoli, E and Sacconi, R and Querques, L and Querques, G},
title = {Artificial intelligence in age-related macular degeneration: state of the art and recent updates.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {121},
pmid = {38491380},
issn = {1471-2415},
mesh = {Humans ; *Artificial Intelligence ; *Macular Degeneration/diagnosis ; Machine Learning ; Tomography, Optical Coherence ; },
abstract = {Age related macular degeneration (AMD) represents a leading cause of vision loss and it is expected to affect 288 million people by 2040. During the last decade, machine learning technologies have shown great potential to revolutionize clinical management of AMD and support research for a better understanding of the disease. The aim of this review is to provide a panoramic description of all the applications of AI to AMD management and screening that have been analyzed in recent past literature. Deep learning (DL) can be effectively used to diagnose AMD, to predict short term risk of exudation and need for injections within the next 2 years. Moreover, DL technology has the potential to customize anti-VEGF treatment choice with a higher accuracy than expert human experts. In addition, accurate prediction of VA response to treatment can be provided to the patients with the use of ML models, which could considerably increase patients' compliance to treatment in favorable cases. Lastly, AI, especially in the form of DL, can effectively predict conversion to GA in 12 months and also suggest new biomarkers of conversion with an innovative reverse engineering approach.},
}
@article {pmid38490689,
year = {2024},
author = {Han, JED and Subramanian, A and Lee, WH and Coker, J and Denniston, AK and Nirantharakumar, K and Adderley, NJ},
title = {Association of sildenafil use with age-related macular degeneration: a retrospective cohort study.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {38490689},
issn = {2397-3269},
mesh = {Male ; Humans ; Sildenafil Citrate/adverse effects ; *Erectile Dysfunction/chemically induced ; Retrospective Studies ; *Diabetes Mellitus, Type 2/drug therapy ; Phosphodiesterase 5 Inhibitors/adverse effects ; *Macular Degeneration/chemically induced ; },
abstract = {OBJECTIVE: Despite significant advances in clinical care and understanding of the underlying pathophysiology, age-related macular degeneration (AMD)-a major cause of global blindness-lacks effective treatment to prevent the irreversible degeneration of photoreceptors leading to central vision loss. Limited studies suggest phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, may prevent AMD by increasing retinal blood flow. This study explores the potential association between sildenafil use and AMD risk in men with erectile dysfunction using UK data.<br><br>METHODS AND ANALYSIS: Using the UK's IQVIA Medical Research Data, the study analysed 31 575 men prescribed sildenafil for erectile dysfunction and no AMD history from 2007 to 2015, matched with a comparator group of 62 155 non-sildenafil users in a 1:2 ratio, over a median follow-up of approximately three years.<br><br>RESULTS: The primary outcome was the incidence of AMD in the two groups. The study found no significant difference in AMD incidence between the sildenafil users and the non-users, with an adjusted hazard ratio (HR) of 0.99 (95% CI 0.84 to 1.16), after accounting for confounders such as age, ethnicity, Townsend deprivation quintile, body mass index category, and diagnosis of hypertension and type 2 diabetes.<br><br>CONCLUSION: The study results indicated no significant association between sildenafil use and AMD prevention in UK men with erectile dysfunction, suggesting sildenafil's protective effect on AMD is likely insignificant.},
}
@article {pmid38490478,
year = {2024},
author = {Malmin, A and Thomseth, VM and Førland, PT and Aass, HCD and Reppe, S and Olsen, MVT and Lindtjørn, B and Chen, X and Haugen, IBK and Utheim, TP and Forsaa, VA},
title = {Tear cytokine levels are reduced in patients treated with intravitreal injections.},
journal = {The ocular surface},
volume = {32},
number = {},
pages = {222-226},
doi = {10.1016/j.jtos.2024.03.004},
pmid = {38490478},
issn = {1937-5913},
mesh = {Humans ; *Tears/metabolism ; *Intravitreal Injections ; Aged ; *Cytokines/metabolism ; Male ; Female ; Middle Aged ; Aged, 80 and over ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; Ranibizumab/administration &amp; dosage/therapeutic use ; Wet Macular Degeneration/drug therapy/metabolism ; Prospective Studies ; },
abstract = {PURPOSE: To investigate cytokine levels in the tear fluid of patients receiving serial intravitreal injections (IVI) with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Concentrations of six cytokines (IFN-&#x3b3;, IL-1&#x3b2;, IL-6, IL-8, TNF and VEGF) in tears of patients receiving anti-VEGF in one eye were assayed using multiplex cytometric bead array. The fellow untreated eye served as control. Tear sampling was performed on a single occasion at a minimum of four weeks after IVI. Patients underwent a pre-IVI antisepsis protocol with povidone-iodine.<br><br>RESULTS: Tear fluid from thirty patients with a mean age of 78.8 years (range 58-90) was assayed. Subjects received a median of 43.5 (range 22-106) IVI in one eye. The median level of IFN-&#x3b3; was 0.33 (interquartile range (IQR) 0.22-0.52) pg/mg of total protein in injected eyes versus 0.41 (IQR 0.21-1.05) pg/mg in fellow eyes (p&#xa0;=&#xa0;0.017). For TNF, a median level of 0.12 (IQR 0.08-0.18) pg/mg of total protein was found in injected eyes versus 0.14 (IQR 0.07-0.33) pg/mg of total protein in fellow eyes (p&#xa0;=&#xa0;0.019). There were no differences between injected and fellow eyes regarding the levels of IL-1&#x3b2;, IL-6, IL-8 and VEGF.<br><br>CONCLUSION: Tear fluid in eyes receiving serial IVI with anti-VEGF and preoperative povidone-iodine antisepsis constitutes lower levels of the pro-inflammatory cytokines IFN-&#x3b3; and TNF compared to fellow eyes. This provides biochemical support of previous findings of reduced signs of inflammation and healthier tear film parameters in patients treated with serial IVI.},
}
@article {pmid38490392,
year = {2024},
author = {Dąbkowska, M and Stukan, I and Kosiorowska, A and Szatanik, A and Łuczkowska, K and Machalińska, A and Machaliński, B},
title = {In vitro and in vivo characterization of human serum albumin-based PEGylated nanoparticles for BDNF and NT3 codelivery.},
journal = {International journal of biological macromolecules},
volume = {265},
number = {Pt 2},
pages = {130726},
doi = {10.1016/j.ijbiomac.2024.130726},
pmid = {38490392},
issn = {1879-0003},
mesh = {Mice ; Humans ; Animals ; *Brain-Derived Neurotrophic Factor ; Tissue Distribution ; Membrane Potentials ; *Polyethylene Glycols ; },
abstract = {The utilization of neurotrophins in medicine shows significant potential for addressing neurodegenerative conditions, such as age-related macular degeneration (AMD). However, the therapeutic use of neurotrophins has been restricted due to their short half-life. Here, we aimed to synthesize PEGylated nanoparticles based on electrostatic-driven interactions between human serum albumin (HSA), a carrier for adsorption; neurotrophin-3 (NT3); and brain-derived neurotrophic factor (BDNF). Electrophoretic (ELS) and multi-angle dynamic light scattering (MADLS) revealed that the PEGylated HSA-NT3-BDNF nanoparticles ranged from 10 to 430 nm in diameter and exhibited a low polydispersity index (<0.4) and a zeta potential of -8 mV. Based on microscale thermophoresis (MST), the estimated dissociation constant (Kd) from the HSA molecule of BDNF was 1.6 μM, and the Kd of NT3 was 732 μM. The nanoparticles were nontoxic toward ARPE-19 and L-929 cells in vitro and efficiently delivered BDNF and NT3. Based on the biodistribution of neurotrophins after intravitreal injection into BALB/c mice, both nanoparticles were gradually released in the mouse vitreous body within 28 days. PEGylated HSA-NT3-BDNF nanoparticles stabilize neurotrophins and maintain this characteristic in vivo. Thus, given the simplicity of the system, the nanoparticles may enhance the treatment of a variety of neurological disorders in the future.},
}
@article {pmid38490292,
year = {2024},
author = {Gu, S and Wu, S and Lin, Z and Han, Z and Mo, K and Huang, H and Li, M and Li, G and Ouyang, H and Wang, L},
title = {Screening and evaluation of antioxidants for retinal pigment epithelial cell protection: L-ergothioneine as a novel therapeutic candidate through NRF2 activation.},
journal = {Experimental eye research},
volume = {242},
number = {},
pages = {109862},
doi = {10.1016/j.exer.2024.109862},
pmid = {38490292},
issn = {1096-0007},
mesh = {*Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *NF-E2-Related Factor 2/metabolism/genetics ; Animals ; *Ergothioneine/pharmacology ; *Antioxidants/pharmacology ; *Oxidative Stress/drug effects ; Mice ; Mice, Inbred C57BL ; Macular Degeneration/drug therapy/metabolism/pathology ; Cells, Cultured ; Humans ; Blotting, Western ; Disease Models, Animal ; Gene Expression Regulation/drug effects ; Reactive Oxygen Species/metabolism ; },
abstract = {The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation. The inhibition of NRF2 abolished EGT's protective effects, suggesting that NRF2 activation contributes to its mechanism of action. In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.},
}
@article {pmid38489843,
year = {2024},
author = {Liu, S and Yan, Z and Huang, Z and Yang, H and Li, J},
title = {Smart Nanocarriers for the Treatment of Retinal Diseases.},
journal = {ACS applied bio materials},
volume = {7},
number = {4},
pages = {2070-2085},
doi = {10.1021/acsabm.3c01289},
pmid = {38489843},
issn = {2576-6422},
mesh = {Humans ; *Retinal Diseases/drug therapy ; Drug Delivery Systems ; Pharmaceutical Preparations ; },
abstract = {Retinal diseases, such as age-related macular degeneration, diabetic retinopathy, and retinoblastoma, stand as the leading causes of irreversible vision impairment and blindness worldwide. Effectively administering drugs for retinal diseases poses a formidable challenge due to the presence of complex ocular barriers and elimination mechanisms. Over time, various approaches have been developed to fabricate drug delivery systems for improving retinal therapy including virus vectors, lipid nanoparticles, and polymers. However, conventional nanocarriers encounter issues related to the controllability, efficiency, and safety in the retina. Therefore, the development of smart nanocarriers for effective or more invasive long-term treatment remains a desirable goal. Recently, approaches have surfaced for the intelligent design of nanocarriers, leveraging specific responses to external or internal triggers and enabling multiple functions for retinal therapy such as topical administration, prolonged drug release, and site-specific drug delivery. This Review provides an overview of prevalent retinal pathologies and related pharmacotherapies to enhance the understanding of retinal diseases. It also surveys recent developments and strategies employed in the intelligent design of nanocarriers for retinal disease. Finally, the challenges of smart nanocarriers in potential clinical retinal therapeutic applications are discussed to inspire the next generation of smart nanocarriers.},
}
@article {pmid38489765,
year = {2024},
author = {Crincoli, E and Catania, F and Sacconi, R and Ribarich, N and Ferrara, S and Parravano, M and Costanzo, E and Querques, G},
title = {DEEP LEARNING FOR AUTOMATIC PREDICTION OF EARLY ACTIVATION OF TREATMENT-NAIVE NONEXUDATIVE MACULAR NEOVASCULARIZATIONS IN AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {8},
pages = {1360-1370},
doi = {10.1097/IAE.0000000000004106},
pmid = {38489765},
issn = {1539-2864},
mesh = {Humans ; *Deep Learning ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; *Fluorescein Angiography/methods ; Aged ; Follow-Up Studies ; Aged, 80 and over ; Wet Macular Degeneration/diagnosis/drug therapy ; Fundus Oculi ; Visual Acuity ; Macula Lutea/diagnostic imaging/pathology ; Retinal Neovascularization/diagnosis/etiology ; },
abstract = {BACKGROUND: Around 30% of nonexudative macular neovascularizations exudate within 2 years from diagnosis in patients with age-related macular degeneration. The aim of this study is to develop a deep learning classifier based on optical coherence tomography (OCT) and OCT angiography (OCTA) to identify nonexudative macular neovascularizations at risk of exudation.<br><br>METHODS: Patients with age-related macular degeneration showing OCTA and fluorescein angiography-documented nonexudative macular neovascularization with a 2-year minimum imaging follow-up were retrospectively selected. Patients showing OCT B-scan-documented macular neovascularization exudation within the first 2 years formed the EX GROUP while the others formed the QU GROUP. ResNet-101, Inception-ResNet-v2, and DenseNet-201 were independently trained on OCTA and OCT B-scan images. Combinations of the six models were evaluated with major and soft voting techniques.<br><br>RESULTS: Eighty-nine eyes of 89 patients with a follow-up of 5.7 &#xb1; 1.5 years were recruited (35 EX GROUP and 54 QU GROUP). Inception-ResNet-v2 was the best performing among the three single convolutional neural networks. The major voting model resulting from the association of the three different convolutional neural networks resulted in an improvement of performance both for OCTA and OCT B-scan (both significantly higher than human graders' performance). The soft voting model resulting from the combination of OCTA and OCT B-scan-based major voting models showed a testing accuracy of 94.4%. Peripheral arcades and large vessels on OCTA en face imaging were more prevalent in the QU GROUP.<br><br>CONCLUSION: Artificial intelligence shows high performances in identifications of nonexudative macular neovascularizations at risk for exudation within the first 2 years of follow-up, allowing better customization of follow-up timing and avoiding treatment delay. Better results are obtained with the combination of OCTA and OCT B-scan image analysis.},
}
@article {pmid38489060,
year = {2024},
author = {Lee, JH and Kim, JH},
title = {Impact of Prolonged Persisting Subretinal Fluid on the Outcome of Aflibercept Treatment in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {40},
number = {2},
pages = {136-143},
doi = {10.1089/jop.2023.0124},
pmid = {38489060},
issn = {1557-7732},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Subretinal Fluid ; Retrospective Studies ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Intravitreal Injections ; *Recombinant Fusion Proteins ; },
abstract = {Purpose: To evaluate the effect of prolonged residual subretinal fluid (SRF) on the outcomes of aflibercept treatment in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Methods: This retrospective study included patients diagnosed with neovascular AMD or PCV who presented with fovea-involving residual SRF that persisted for a minimum of 6 months while undergoing aflibercept treatment. Changes in best-corrected visual acuity (BCVA) during persistent SRF were evaluated. The factors associated with the risk of visual deterioration during this period were also investigated. Results: In total, 135 patients were included in this study. During this period, the duration of the presence of residual SRF was 17.1 ± 10.3 months and mean injection interval was 2.6 ± 0.7 months. The mean BCVA was changed from 0.30 ± 0.23(Snellen equivalents, 20/39) to 0.36 ± 0.28 (20/45). In 18 (13.3%) patients, ≥2 lines of visual deterioration was noted. The duration of persisting SRF (P = 0.008) and mean height of SRF (P = 0.005) were significantly associated with a high risk of visual deterioration. Among the 80 patients with mean SRF height <100 μm, ≥2 lines of visual deterioration were noted in 4 (5.0%) patients. Among 41 patients with the mean SRF height ≥100 μm and <200 μm and 14 patients with the mean SRF height ≥200 μm, the visual deterioration was noted in 8 (19.5%) and 6 (42.9%) patients, respectively. Conclusions: In cases of neovascular AMD or PCV in which SRF persists without complete resolution during treatment, minimizing the duration of persistent SRF and mean height of SRF is recommended to mitigate the risk of visual deterioration. ClinicalTrials.gov Identifiers: NCT05662943 (https://clinicaltrials.gov/study/NCT05662943?cond=type%201%20macular%20neovascularization&amp;rank=2).},
}
@article {pmid38489005,
year = {2025},
author = {Ye, SS and Wang, JN and Zhao, YF and Dai, LS and Zhang, JZ and Zuo, YQ and Song, JT},
title = {Purinergic P2X7 receptor involves in anti-retinal photodamage effects of berberine.},
journal = {Purinergic signalling},
volume = {21},
number = {4},
pages = {675-685},
pmid = {38489005},
issn = {1573-9546},
support = {202001//Eye Hospital of China Academy of Chinese Medical Sciences Scientific Research fund/ ; CI2021A02608//China Academy of Chinese Medical Sciences Innovation Fund/ ; },
mesh = {Animals ; *Receptors, Purinergic P2X7/metabolism/drug effects ; *Berberine/pharmacology/therapeutic use ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Retinal Degeneration/metabolism/drug therapy/pathology ; *Retina/drug effects/metabolism/radiation effects ; Male ; Light/adverse effects ; },
abstract = {Berberine (BBR) is a Chinese herb with antioxidant and anti-inflammatory properties. In a previous study, we found that BBR had a protective effect against light-induced retinal degeneration in BALB/c mice. The purinergic P2X7 receptor (P2X7R) plays a key role in retinal degeneration via inducing oxidative stress, inflammatory changes, and cell death. The aim of this study was to investigate whether BBR can induce protective effects in light damage experiments and whether P2X7R can get involved in these effects. C57BL/6 J mice and P2X7 knockout (KO) mice on the C57BL/6 J background were used. We found that BBR preserved the outer nuclear layer (ONL) thickness and retinal ganglion cells following light stimulation. Furthermore, BBR significantly suppressed photoreceptor apoptosis, pro-apoptotic c-fos expression, pro-inflammatory responses of Mϋller cells, and inflammatory factors (TNF-α, IL-1β). In addition, protein levels of P2X7R were downregulated in BBR-treated mice. Double immunofluorescence showed that BBR reduced overexpression of P2X7R in retinal ganglion cells and Mϋller cells. Furthermore, BBR combined with the P2X7R agonist BzATP blocked the effects of BBR on retinal morphology and photoreceptor apoptosis. However, in P2X7 KO mice, BBR had an additive effect resulting in thicker ONL and more photoreceptors. The data suggest that the P2X7 receptor is involved in retinal light damage, and BBR inhibits this process by reducing histological impairment, cell death, and inflammatory responses.},
}
@article {pmid38487969,
year = {2024},
author = {Iyer, S and Bhat, I and Bangera Sheshappa, M},
title = {Lutein and the Underlying Neuroprotective Promise against Neurodegenerative Diseases.},
journal = {Molecular nutrition &amp; food research},
volume = {68},
number = {13},
pages = {e2300409},
doi = {10.1002/mnfr.202300409},
pmid = {38487969},
issn = {1613-4133},
mesh = {*Lutein/pharmacology ; Humans ; *Neuroprotective Agents/pharmacology ; Animals ; *Alzheimer Disease/prevention &amp; control/drug therapy ; *Parkinson Disease/prevention &amp; control/drug therapy ; *Antioxidants/pharmacology ; *Neurodegenerative Diseases/prevention &amp; control/drug therapy ; Oxidative Stress/drug effects ; Brain/drug effects/metabolism ; },
abstract = {Alzheimer's disease (AD) and Parkinson's diseases (PD) are the two most common progressive neurodegenerative diseases with limited knowledge on their cause and, presently, have no cure. There is an existence of multiple treatment methods that target only the symptoms temporarily and do not stop the progression or prevent the onset of disease. Neurodegeneration is primarily attributed to the natural process of aging and the deleterious effects of heightened oxidative stress within the brain, whether via direct or indirect mechanisms. Emerging evidence suggests that certain nutritional aspects play a crucial role in the prevention and management of neurodegenerative diseases. Lutein, a dietary carotenoid, has been studied for its antioxidant properties for more than a decade with several applications against age-related macular degeneration. It is high antioxidant potential and selective accumulation in the brain makes it a versatile compound for combatting various neurodegenerative diseases. In this review, the studies exhibiting neuroprotective properties of lutein against neurodegenerative conditions, more specifically AD and PD in various model systems as well as clinical observations have been reviewed. Accordingly, the concerns associated with lutein absorption and potential strategies to improve its bioavailability have been discussed.},
}
@article {pmid38486642,
year = {2024},
author = {Okonkwo, ON and Hassan, AO and Bogunjoko, T and Akinye, A and Akanbi, T and Agweye, C},
title = {Impact of Coronavirus Disease 2019 on Intravitreal Antivascular Endothelial Growth Factor Injection Rates in Nigerians.},
journal = {Journal of the West African College of Surgeons},
volume = {14},
number = {1},
pages = {48-53},
pmid = {38486642},
issn = {2992-5827},
abstract = {AIM: To quantify the impact of coronavirus disease 2019 (COVID-19) on the rate of intravitreal antivascular endothelial growth factor (VEGF) injections (IVI) in eye hospitals in Nigeria.<br><br>MATERIALS AND METHODS: A retrospective, observational, comparative study. The IVIs given 12 months before (pre-COVID) and 12 months after the first announcement of the COVID-19 lockdown (COVID) in Nigeria in four hospitals were used as the sample for this study. All eyes were treatment na&#xef;ve. We determined the total number of all anti-VEGF injections, the number given for each indication, and the number of each type of the three anti-VEGFs given. A comparison of the presenting vision in IVI eyes between the two eras and the visual outcome of the IVI treatment was made. Data were analyzed using the SPSS version 22 to determine statistical significance.<br><br>RESULTS: Male/female ratio, pre-COVID 63.4%/36.6% and COVID 58.6%/41.4% (P = 0.123). Age, pre-COVID 61.3 (SD 12.9) 9-95 years and COVID 57.5 (SD 16.4) 0.15-95 years. There was a 15.3% (81 eyes) reduction in the number of eyes between pre-COVID and COVID eras (528 and 447 eyes, respectively). Likewise, the number of IVIs reduced by 26% (221 IVIs) from 850 pre-COVID to 629 COVID, P = 0.005. A comparison of the proportion of eyes in the four clinic locations between the two eras was not statistically significant (P = 0.148). The commonest indication was proliferative diabetic retinopathy in both eras, 208 versus 178 eyes (323 versus 226 IVIs). Bevacizumab, Ranibizumab, and Aflibercept were given in the following proportions 60.2%, 22.3%, and 17.4% (pre-COVID) versus 60.2%, 31.5%, and 8.3% (COVID), P = 0.000. Presenting visual acuity was >6/60 in 67.4% of eyes (pre-COVID) versus 59.4% of eyes (COVID), P = 0.039. Vision improved in 51.3% of eyes (pre-COVID) versus 47.7% (COVID); there was no significant difference in visual outcome comparing both eras, P = 0.972.<br><br>CONCLUSION: COVID-19 significantly reduced the number of eyes and IVIs. Eyes had worse presenting visual acuity during the COVID era; however, treatment outcome was comparable between COVID and pre-COVID eras.},
}
@article {pmid38485865,
year = {2024},
author = {Bhatt, P and Narvekar, P and Lalani, R and Chougule, MB and Pathak, Y and Sutariya, V},
title = {Correction to: An in vitro Assessment of Thermo-Reversible Gel Formulation Containing Sunitinib Nanoparticles for Neovascular Age-Related Macular Degeneration.},
journal = {AAPS PharmSciTech},
volume = {25},
number = {3},
pages = {62},
doi = {10.1208/s12249-024-02782-1},
pmid = {38485865},
issn = {1530-9932},
}
@article {pmid38485215,
year = {2024},
author = {Tabuchi, H and Engelmann, J and Maeda, F and Nishikawa, R and Nagasawa, T and Yamauchi, T and Tanabe, M and Akada, M and Kihara, K and Nakae, Y and Kiuchi, Y and Bernabeu, MO},
title = {Using artificial intelligence to improve human performance: efficient retinal disease detection training with synthetic images.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {10},
pages = {1430-1435},
pmid = {38485215},
issn = {1468-2079},
mesh = {Humans ; *Artificial Intelligence ; *Retinal Diseases/diagnosis ; *Ophthalmology/education ; Clinical Competence ; Diagnostic Techniques, Ophthalmological ; },
abstract = {BACKGROUND: Artificial intelligence (AI) in medical imaging diagnostics has huge potential, but human judgement is still indispensable. We propose an AI-aided teaching method that leverages generative AI to train students on many images while preserving patient privacy.<br><br>METHODS: A web-based course was designed using 600 synthetic ultra-widefield (UWF) retinal images to teach students to detect disease in these images. The images were generated by stable diffusion, a large generative foundation model, which we fine-tuned with 6285 real UWF images from six categories: five retinal diseases (age-related macular degeneration, glaucoma, diabetic retinopathy, retinal detachment and retinal vein occlusion) and normal. 161 trainee orthoptists took the course. They were evaluated with two tests: one consisting of UWF images and another of standard field (SF) images, which the students had not encountered in the course. Both tests contained 120 real patient images, 20 per category. The students took both tests once before and after training, with a cool-off period in between.<br><br>RESULTS: On average, students completed the course in 53&#x2009;min, significantly improving their diagnostic accuracy. For UWF images, student accuracy increased from 43.6% to 74.1% (p<0.0001 by paired t-test), nearly matching the previously published state-of-the-art AI model's accuracy of 73.3%. For SF images, student accuracy rose from 42.7% to 68.7% (p<0.0001), surpassing the state-of-the-art AI model's 40%.<br><br>CONCLUSION: Synthetic images can be used effectively in medical education. We also found that humans are more robust to novel situations than AI models, thus showcasing human judgement's essential role in medical diagnosis.},
}
@article {pmid38485214,
year = {2024},
author = {Ricardi, F and Oakley, J and Russakoff, D and Boscia, G and Caselgrandi, P and Gelormini, F and Ghilardi, A and Pintore, G and Tibaldi, T and Marolo, P and Bandello, F and Reibaldi, M and Borrelli, E},
title = {Validation of a deep learning model for automatic detection and quantification of five OCT critical retinal features associated with neovascular age-related macular degeneration.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {10},
pages = {1436-1442},
doi = {10.1136/bjo-2023-324647},
pmid = {38485214},
issn = {1468-2079},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Deep Learning ; *Wet Macular Degeneration/diagnosis ; Male ; Female ; Aged ; *ROC Curve ; Aged, 80 and over ; Subretinal Fluid/diagnostic imaging ; Retinal Drusen/diagnosis ; Retina/diagnostic imaging/pathology ; Area Under Curve ; },
abstract = {PURPOSE: To develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: 300 optical coherence tomography volumes from subject eyes with nAMD were collected. Images were manually segmented for the presence of five crucial nAMD features: intraretinal fluid, subretinal fluid, subretinal hyperreflective material, drusen/drusenoid pigment epithelium detachment (PED) and neovascular PED. A deep learning architecture based on a U-Net was trained to perform automatic segmentation of these retinal biomarkers and evaluated on the sequestered data. The main outcome measures were receiver operating characteristic curves for detection, summarised using the area under the curves (AUCs) both on a per slice and per volume basis, correlation score, enface topography overlap (reported as two-dimensional (2D) correlation score) and Dice coefficients.<br><br>RESULTS: The model obtained a mean (&#xb1;SD) AUC of 0.93 (&#xb1;0.04) per slice and 0.88 (&#xb1;0.07) per volume for fluid detection. The correlation score (R[2]) between automatic and manual segmentation obtained by the model resulted in a mean (&#xb1;SD) of 0.89 (&#xb1;0.05). The mean (&#xb1;SD) 2D correlation score was 0.69 (&#xb1;0.04). The mean (&#xb1;SD) Dice score resulted in 0.61 (&#xb1;0.10).<br><br>CONCLUSIONS: We present a fully automated segmentation model for five features related to nAMD that performs at the level of experienced graders. The application of this model will open opportunities for the study of morphological changes and treatment efficacy in real-world settings. Furthermore, it can facilitate structured reporting in the clinic and reduce subjectivity in clinicians' assessments.},
}
@article {pmid38485112,
year = {2024},
author = {Broadhead, GK and Grigg, J and McCluskey, PJ and Hong, T and Schlub, TE and Chu, E and Chang, AA},
title = {Saffron therapy for the ongoing treatment of age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {38485112},
issn = {2397-3269},
mesh = {Humans ; Antioxidants ; *Crocus ; Dietary Supplements ; *Macular Degeneration/drug therapy ; Visual Acuity ; },
abstract = {OBJECTIVE: To assess the long-term efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD).<br><br>METHODS AND ANALYSIS: Open-label, extension trial of 93 adults (>50 years) with mild/moderate AMD and vision >20/70 Snellen equivalent in at least 1 eye. Exclusion criteria included confounding visual lesions or significant gastrointestinal disease impairing absorption.Participants were given oral saffron supplementation (20&#x2009;mg/day) for 12 months. Those already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these.Primary outcomes included changes in multifocal electroretinogram (mfERG) response density and latency, and changes in best-corrected visual acuity (BCVA). Secondary outcomes included safety outcomes, changes in mfERG and BCVA among participants on AREDS supplements and changes in microperimetry.<br><br>RESULTS: At 12 months, mean mfERG response density was significantly higher in rings 1, 2 and overall (p<0.001 for all) but not in rings 3-6, and there was no difference in response between those taking AREDS supplements and those not (p>0.05). Mean mfERG latency was not significantly different in any of rings 1-6 or overall (p>0.05 for all), again with no difference between those taking AREDS supplements or not (p>0.05). Mean BCVA was 1.6 letters worse (p<0.05) with no difference between those on AREDS supplements or not, and this may have been related to cataract progression. No saffron-related serious adverse events were detected.<br><br>CONCLUSION: Saffron supplementation modestly improved mfERG responses in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.},
}
@article {pmid38484787,
year = {2024},
author = {Skalicky, N and Hatz-Wurziger, K},
title = {Long-term Follow-Up and Regeneration of Retinal Pigment Epithelium (RPE) after Tears of the Epithelium in Exudative Age-Related Macular Degeneration (AMD).},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {241},
number = {4},
pages = {453-458},
pmid = {38484787},
issn = {1439-3999},
mesh = {Humans ; Female ; Male ; *Retinal Pigment Epithelium/pathology/physiopathology/diagnostic imaging ; Follow-Up Studies ; Aged, 80 and over ; Retrospective Studies ; Aged ; *Retinal Perforations/physiopathology ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Visual Acuity/physiology ; Tomography, Optical Coherence ; Regeneration/physiology ; Longitudinal Studies ; Treatment Outcome ; Vision Disorders/etiology/physiopathology ; Angiogenesis Inhibitors ; },
abstract = {BACKGROUND: The goals of this study are to evaluate potential long-term visual deterioration associated with retinal pigment epithelial (RPE) tears in patients with neovascular age-related macular degeneration (nAMD) and to find treatment-related and morphological factors that might influence the outcomes.<br><br>PATIENTS AND METHODS: This retrospective study enrolled 21 eyes of 21 patients from the database of Vista Eye Clinic Binningen, Switzerland, diagnosed with RPE tears, as confirmed by spectral domain optical coherence tomography (SD-OCT), with a minimum follow-up period of 12 months. Treatment history before and after RPE rupture with anti-VEGF therapy, visual acuity, and imaging (SD-OCT) were analyzed and statistically evaluated for possible correlations.<br><br>RESULTS: Mean patient age was 80.5&#x2009;&#xb1;&#x2009;6.2 years. The mean length of total follow-up was 39.7&#x2009;&#xb1;&#x2009;13.9 months. The mean pigment epithelial detachment (PED) height increased by 363.8&#x2009;&#xb1;&#x2009;355.5&#x2009;&#xb5;m from the first consultation to 562.8&#x2009;&#xb1;&#x2009;251.5&#x2009;&#xb5;m at the last consultation prior to rupture. Therefore, a higher risk of RPE rupture is implied as a result of an increase in PED height (p&#x2009;=&#x2009;0.004, n&#x2009;=&#x2009;14). The mean visual acuity before rupture was 66.2&#x2009;&#xb1;&#x2009;16.0 letters. Mean visual acuity deteriorated to 60.8&#x2009;&#xb1;&#x2009;18.6 letters at the first consultation after rupture (p&#x2009;=&#x2009;0.052, n&#x2009;=&#x2009;21). A statistically nonsignificant decrease in vision was noted in the follow-up period. After 2 years, the mean BCVA decreased by 10.5&#x2009;&#xb1;&#x2009;23.7 ETDRS letters (p&#x2009;=&#x2009;0.23, n&#x2009;=&#x2009;19). PED characteristics before rupture and amount of anti-VEGF injections after rupture did not affect the visual outcome. None of the 21 patients included in our study showed a visual improvement in the long-term follow-up. RPE atrophy increased significantly from 3.35&#x2009;&#xb1;&#x2009;2.94&#x2009;mm[2] (baseline) to 6.81&#x2009;&#xb1;&#x2009;6.25&#x2009;mm[2] over the course of 2 years (p&#x2009;=&#x2009;0.000&#x200a;013, n&#x2009;=&#x2009;20).<br><br>CONCLUSIONS: The overall mean vision decrease after rupture was without statistical significance. There was no significant change in BCVA at the 2-year follow-up, independent of the amount of anti-VEGF injections provided. In this study, there was a significant increase in RPE defect over a follow-up of 2 years, implying progression of contraction of RPE and/or macular atrophy.},
}
@article {pmid38484366,
year = {2024},
author = {Ji, Y and Zuo, C and Liao, N and Yao, L and Yang, R and Chen, H and Wen, F},
title = {Identification of key lncRNAs in age-related macular degeneration through integrated bioinformatics and experimental validation.},
journal = {Aging},
volume = {16},
number = {6},
pages = {5435-5451},
pmid = {38484366},
issn = {1945-4589},
mesh = {Humans ; *RNA, Long Noncoding/genetics ; *MicroRNAs/genetics ; *Macular Degeneration/genetics/pathology ; Computational Biology ; RNA, Messenger/genetics ; Gene Regulatory Networks ; },
abstract = {This study aimed to identify key long noncoding RNAs (lncRNAs) in age-related macular degeneration (AMD) patients and to identify relevant pathological mechanisms of AMD development. We identified 407 differentially expressed mRNAs and 429 differentially expressed lncRNAs in retinal pigment epithelium (RPE) and retina in the macular region of AMD patients versus controls (P < 0.05 and |log2FC| > 0.585) from GSE135092. A total of 14 key differentially expressed mRNAs were obtained through external data validation from GSE115828. A miRNA-mRNA and miRNA-lncRNA network containing 52 lncRNA nodes, 49 miRNA nodes, 14 mRNA nodes and 351 edges was constructed via integrated analysis of these components. Finally, the LINC00276-miR-619-5p-IFIT3 axis was identified via protein-protein network analysis. In the t-BH-induced ARPE-19 senescent cell model, LINC00276 and IFIT3 were downregulated. Overexpression of LINC00276 could accelerate cell migration in combination with IFIT3 upregulation. This compelling finding suggests that LINC00276 plays an influential role in the progression of AMD, potentially through modulating senescence processes, thereby setting a foundation for future investigative efforts to verify this relationship.},
}
@article {pmid38483712,
year = {2024},
author = {Wang, X and Wang, T and Kaneko, S and Kriukov, E and Lam, E and Szczepan, M and Chen, J and Gregg, A and Wang, X and Fernandez-Gonzalez, A and Mitsialis, SA and Kourembanas, S and Baranov, P and Sun, Y},
title = {Photoreceptors inhibit pathological retinal angiogenesis through transcriptional regulation of Adam17 via c-Fos.},
journal = {Angiogenesis},
volume = {27},
number = {3},
pages = {379-395},
pmid = {38483712},
issn = {1573-7209},
support = {R01HL146128/GF/NIH HHS/United States ; R01 EY029238/EY/NEI NIH HHS/United States ; P50 HD105351/HD/NICHD NIH HHS/United States ; R01EY030140, R01EY029238//NIH/NEI/ ; R01 EY030140/EY/NEI NIH HHS/United States ; R01 HL146128/HL/NHLBI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; U24 EY029893/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Retinal Neovascularization/metabolism/pathology/genetics ; *ADAM17 Protein/metabolism/genetics ; *Proto-Oncogene Proteins c-fos/metabolism/genetics ; Mice ; Humans ; Retinopathy of Prematurity/metabolism/pathology/genetics ; Mice, Inbred C57BL ; Transcription, Genetic ; Gene Expression Regulation ; Retinal Vessels/metabolism/pathology ; Retinal Rod Photoreceptor Cells/metabolism/pathology ; Disease Models, Animal ; Angiogenesis ; },
abstract = {Pathological retinal angiogenesis profoundly impacts visual function in vascular eye diseases, such as retinopathy of prematurity (ROP) in preterm infants and age-related macular degeneration in the elderly. While the involvement of photoreceptors in these diseases is recognized, the underlying mechanisms remain unclear. This study delved into the pivotal role of photoreceptors in regulating abnormal retinal blood vessel growth using an oxygen-induced retinopathy (OIR) mouse model through the c-Fos/A disintegrin and metalloprotease 17 (Adam17) axis. Our findings revealed a significant induction of c-Fos expression in rod photoreceptors, and c-Fos depletion in these cells inhibited pathological neovascularization and reduced blood vessel leakage in the OIR mouse model. Mechanistically, c-Fos directly regulated the transcription of Adam17 a shedding protease responsible for the production of bioactive molecules involved in inflammation, angiogenesis, and cell adhesion and migration. Furthermore, we demonstrated the therapeutic potential by using an adeno-associated virus carrying a rod photoreceptor-specific short hairpin RNA against c-fos which effectively mitigated abnormal retinal blood vessel overgrowth, restored retinal thickness, and improved electroretinographic (ERG) responses. In conclusion, this study highlights the significance of photoreceptor c-Fos in ROP pathology, offering a novel perspective for the treatment of this disease.},
}
@article {pmid38483688,
year = {2024},
author = {Özen, O and Koçak Altıntaş, AG},
title = {Can objective parameters in optical coherence tomography be useful markers in the treatment and follow-up of type 1 and type 2 macular neovascularizations related to neovascular age-related macular degeneration?.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {134},
pmid = {38483688},
issn = {1573-2630},
mesh = {Humans ; Angiogenesis Inhibitors ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Retrospective Studies ; Fluorescein Angiography/methods ; *Retinal Neovascularization/drug therapy ; Intravitreal Injections ; *Macular Degeneration/complications ; *Cytomegalovirus Infections/complications ; },
abstract = {PURPOSE: The aim of this study was to compare the responses of type 1 and type 2 macular neovascularizations (MNV) caused by neovascular type age-related macular degeneration (n-AMD) to intravitreal anti-vascular endothelial growth factor (VEGF) treatments using quantitative parameters determined by optical coherence tomography (OCT). Additionally, it was also intended to assess the connections between these quantitative parameters and changes in best-corrected visual acuity (BCVA) and the number of intravitreal anti-VEGF injections required within a year.<br><br>MATERIALS AND METHODS: In our retrospective and observational study, the data of 90 eyes of 90 patients diagnosed with n-AMD and treated with intravitreal anti-VEGF with the "Pro re nata" method were evaluated. Subtypes of existing MNVs were distinguished with previously taken optical coherence tomography angiography (OCTA) images. In spectral domain OCT examinations, central macular thickness (CMT) and central macular volume (CMV) values were recorded at baseline and 12th month. The number of intravitreal anti-VEGF injections during the 12&#xa0;month follow-up period was also recorded for each patient. Obtained data were compared between MNV types.<br><br>RESULTS: Of the n-AMD cases examined in the study, 56.66% had type 1 MNV and 43.34% had type 2 MNV. The mean baseline BCVA logMAR values in eyes with type 2 MNV (1.15&#x2009;&#xb1;&#x2009;0.43) were higher than those observed in eyes with type 1 MNV (0.76&#x2009;&#xb1;&#x2009;0.42) (p&#x2009;=&#x2009;0.001). Similarly, mean baseline CMT and CMV values in eyes with type 2 MNV were higher than those observed in eyes with type 1 MNV (respectively 424.89&#x2009;&#xb1;&#x2009;49.46&#xa0;&#x3bc;m vs. 341.39&#x2009;&#xb1;&#x2009;37.06&#xa0;&#x3bc;m; 9.17&#x2009;&#xb1;&#x2009;0.89 &#x3bc;m[3] vs. 8.49&#x2009;&#xb1;&#x2009;0.53 &#x3bc;m[3]; p&#x2009;<&#x2009;0.05). After 12&#xa0;months of treatment, logMAR values of BCVA (0.86&#x2009;&#xb1;&#x2009;0.42) in subjects with type 2 MNV were higher than those in subjects with type 1 MNV (0.57&#x2009;&#xb1;&#x2009;0.37) (p&#x2009;=&#x2009;0.001). Mean CMT and CMV values at 12th month in subjects with type 2 MNV (379.11&#x2009;&#xb1;&#x2009;46.36&#xa0;&#x3bc;m and 8.66&#x2009;&#xb1;&#x2009;0.79 &#x3bc;m[3], respectively) were observed to be higher than those with type 1 MNV (296.95&#x2009;&#xb1;&#x2009;33.96&#xa0;&#x3bc;m and 8.01&#x2009;&#xb1;&#x2009;0.52 mm[3], respectively) (p&#x2009;<&#x2009;0.05). In type 2 MNVs, positive correlations were observed between both baseline and 12th month BCVA logMAR values and baseline CMV (p&#x2009;<&#x2009;0.05). Similarly, in type 2 MNVs, a positive correlation was observed between 12th month BCVA logMAR values and 12th month CMV (p&#x2009;<&#x2009;0.05). The total number of intravitreal anti-VEGF injections at 12&#xa0;months was similar in both groups (p&#x2009;=&#x2009;0.851).<br><br>CONCLUSION: In this study, in which we performed a subtype analysis of MNV cases, we observed that the visual function was worse at the beginning and the end of the 12th month, and the CMT and CMV values were higher in the type 2 MNV group compared to the type 1 MNV cases. In addition, we found significant correlations between BCVA logMAR values and CMV values in type 2 MNV cases. In the follow-up of these cases, CMT, which is a more widely used quantitative method, and CMV, which is a newer OCT measurement parameter, may be more useful in patient follow-up and evaluation of treatment efficacy, especially for type 2 MNV cases.},
}
@article {pmid38483611,
year = {2024},
author = {Koizumi, H and Gomi, F and Tsujikawa, A and Honda, S and Mori, R and Ochi, H and Iwasaki, K and Okada, AA and , },
title = {Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 2-year results from the Japan subgroup of the phase III TENAYA trial.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {8},
pages = {2439-2448},
pmid = {38483611},
issn = {1435-702X},
mesh = {Humans ; *Intravitreal Injections ; *Visual Acuity ; Male ; Double-Blind Method ; Female ; Japan/epidemiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Middle Aged ; Aged ; Follow-Up Studies ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Tomography, Optical Coherence ; Recombinant Fusion Proteins/administration &amp; dosage ; Time Factors ; Dose-Response Relationship, Drug ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Drug Administration Schedule ; Fluorescein Angiography ; },
abstract = {PURPOSE: To evaluate 2-year efficacy, durability, and safety of faricimab in the TENAYA Japan subgroup and pooled global TENAYA/LUCERNE cohort of patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Subgroup analysis of TENAYA/LUCERNE (NCT03823287/NCT03823300): phase III, multicentre, randomised, active comparator-controlled, double-masked, non-inferiority trials. Treatment-na&#xef;ve patients aged&#x2009;&#x2265;&#x2009;50&#xa0;years with nAMD were randomised (1:1) to intravitreal faricimab (6.0&#xa0;mg up to every 16&#xa0;weeks [Q16W] after 4 initial Q4W doses) or aflibercept (2.0&#xa0;mg Q8W after 3 initial Q4W doses). Outcomes were assessed through year 2 for the TENAYA Japan subgroup (N&#x2009;=&#x2009;133) and global pooled TENAYA/LUCERNE cohort (N&#x2009;=&#x2009;1329).<br><br>RESULTS: Vision and anatomic improvements achieved with faricimab at year 1 were maintained over 2&#xa0;years and were generally comparable between the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Adjusted mean best-corrected visual acuity (BCVA) change from baseline at year 2 for the TENAYA Japan subgroup and global pooled TENAYA/LUCERNE cohort was +7.1 (3.7-10.5) and +4.4 (3.2-5.5) letters in the faricimab arm, respectively, and +5.2 (1.9-8.6) and +4.3 (3.1-5.4) letters in the aflibercept arm, respectively. At week 112, the proportion of faricimab-treated patients on Q16W dosing was 61.0% and 63.1% in the TENAYA Japan subgroup and pooled TENAYA/LUCERNE cohort. Faricimab was well tolerated through year 2.<br><br>CONCLUSION: Year 2 TENAYA Japan subgroup findings for faricimab were generally consistent with the pooled global TENAYA/LUCERNE results in patients with nAMD. Vision and anatomical benefits with faricimab were similar to those with aflibercept but with fewer injections.},
}
@article {pmid38483610,
year = {2024},
author = {Rai, BB and Sabeti, F and van Kleef, JP and Carle, CF and Rohan, EMF and Essex, RW and Barry, RC and Maddess, T},
title = {Comparing 2-dimensional macular pigment optical density with objective and subjective perimetry and visual acuity in age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {8},
pages = {2449-2459},
pmid = {38483610},
issn = {1435-702X},
support = {PG2018040//Rebecca L. Cooper Medical Research Foundation/ ; BTBR100196//MRFF Biotechnology Bridge grant/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; *Visual Acuity/physiology ; *Visual Field Tests/methods ; Male ; Aged ; *Macular Pigment/metabolism ; *Visual Fields/physiology ; *Macula Lutea/diagnostic imaging ; Macular Degeneration/diagnosis/physiopathology/metabolism ; ROC Curve ; Follow-Up Studies ; },
abstract = {PURPOSE: To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA).<br><br>METHODS: The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99&#x2009;&#xb1;&#x2009;0.16&#xa0;years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC).<br><br>RESULTS: In 58 eyes of 29 subjects (71.6&#x2009;&#xb1;&#x2009;6.3&#xa0;years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland-Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0&#x2009;&#xb1;&#x2009;6.3%, outperforming OFA, Matrix perimetry, and BCVA.<br><br>CONCLUSIONS: MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.},
}
@article {pmid38483382,
year = {2024},
author = {Keenan, TDL and Bailey, C and Abraham, M and Orndahl, C and Menezes, S and Bellur, S and Arunachalam, T and Kangale-Whitney, C and Srinivas, S and Karamat, A and Nittala, M and Cunningham, D and Jeffrey, BG and Wiley, HE and Thavikulwat, AT and Sadda, S and Cukras, CA and Chew, EY and Wong, WT},
title = {Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration: A Nonrandomized Controlled Trial.},
journal = {JAMA ophthalmology},
volume = {142},
number = {4},
pages = {345-355},
pmid = {38483382},
issn = {2168-6173},
mesh = {Humans ; Female ; Aged ; *Geographic Atrophy/drug therapy ; Minocycline/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Prospective Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Fluorescein Angiography ; },
abstract = {IMPORTANCE: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable.<br><br>OBJECTIVE: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD.<br><br>This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023.<br><br>INTERVENTION: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase.<br><br>RESULTS: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P&#x2009;=&#x2009;.39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P&#x2009;=&#x2009;.44) for visual acuity and 0.7 &#x3bc;m per month (-0.4 to 1.8; P&#x2009;=&#x2009;.20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants).<br><br>CONCLUSIONS AND RELEVANCE: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.},
}
@article {pmid38483361,
year = {2024},
author = {Liu, W and Zhang, C and Jiang, F and Tan, Y and Qin, B},
title = {From theory to therapy: a bibliometric and visual study of stem cell advancements in age-related macular degeneration.},
journal = {Cytotherapy},
volume = {26},
number = {6},
pages = {616-631},
doi = {10.1016/j.jcyt.2024.02.022},
pmid = {38483361},
issn = {1477-2566},
mesh = {Humans ; *Bibliometrics ; Embryonic Stem Cells/cytology/transplantation ; Induced Pluripotent Stem Cells/cytology ; *Macular Degeneration/therapy ; *Stem Cell Transplantation/methods ; },
abstract = {BACKGROUND AIMS: Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and emerging areas in stem cell and AMD research through bibliometric analysis.<br><br>METHODS: This study analyzed articles and reviews on stem cells and AMD from 2000 to 2022, sourced from the Web of Science Core Collection. We used VOSviewer and CiteSpace for analysis and visualization of data pertaining to countries, institutions, authors, journals, references and key words. Statistical analyses were conducted using R language and Microsoft Excel 365.<br><br>RESULTS: In total, 539 publications were included, indicating an increase in global literature on stem cells and AMD from 2000 to 2022. The USA was the leading contributor, with 239 papers and the highest H-index, also the USA had the highest average citation rate per article (59.82). Notably, 50% of the top 10 institutions were from the USA, with the University of California system being the most productive. Key authors included Masayo Takahashi, Michiko Mandai, Dennis Clegg, Pete J. Coffey, Boris Stanzel, and Budd A. Tucker. Investigative Ophthalmology &amp; Visual Science published the majority of relevant papers (n = 27). Key words like "clinical trial," "stem cell therapy," "retinal organoid," and "retinal progenitor cells" were predominant.<br><br>CONCLUSIONS: Research on stem cells and AMD has grown significantly, highlighting the need for increased global cooperation. Current research prioritizes the relationship between "ipsc," "induced pluripotent stem cell," "cell culture," and "human embryonic stem cell." As stem cell culture and safety have advanced, focus has shifted to prognosis and complications post-transplantation, signifying the movement of stem cell research from labs to clinical settings.},
}
@article {pmid38480762,
year = {2024},
author = {Nam, SW and Noh, H and Yoon, JM and Ham, DI},
title = {Advanced age-related macular degeneration and risk factors in eyes with pachydrusen.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {6132},
pmid = {38480762},
issn = {2045-2322},
mesh = {Humans ; *Retinal Drusen/epidemiology/etiology ; Angiogenesis Inhibitors ; Retrospective Studies ; Longitudinal Studies ; Fluorescein Angiography ; Tomography, Optical Coherence/adverse effects ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/complications ; Risk Factors ; },
abstract = {The risk of progression to advanced age-related macular degeneration (AMD) varies depending on the type of drusen. This retrospective longitudinal study included 248 eyes of 156 patients with pachydrusen without advanced AMD at baseline. Macular neovascularization (MNV) and geographic atrophy (GA) were evaluated. Risk factors for progression to advanced AMD were determined using multivariate Cox regression analysis. The mean age at baseline was 65.4 ± 9.1 years, and the mean follow-up duration was 6.40 ± 3.58 years. The mean total number of pachydrusen and macular pachydrusen were 4.10 ± 2.85 and 2.27 ± 1.81 per eye, respectively. Pachydrusen was accompanied by other types of drusen in 4.8% (12 eyes) of eyes at baseline. During follow-up, MNVs occurred in 2.8% (seven eyes), including polypoidal choroidal vasculopathy (PCV six eyes); however, no GA occurred. Regarding risk factors for progression to neovascular AMD, age (p = 0.023) and macular pigmentary changes (p = 0.014) were significantly associated with MNV development. The cumulative incidence of MNV was significantly higher in the group with macular pigmentary changes (17.39% vs. 0.57% at 10 years; p = 0.0005). The number of macular pachydrusen and the presence of MNV in the fellow eye did not show a statistically significant relationship with MNV development. Age and macular pigmentary changes are risk factors for MNV development in the eyes with pachydrusen. Eyes with pachydrusen appear to have a risk profile for advanced AMD that is different from that of AMD eyes with drusen or drusenoid deposits other than pachydrusen.},
}
@article {pmid38476863,
year = {2024},
author = {Kim, JS},
title = {Capsular Block Syndrome after an Intravitreal Injection of Ranibizumab: A Case Report.},
journal = {Case reports in ophthalmology},
volume = {15},
number = {1},
pages = {196-201},
pmid = {38476863},
issn = {1663-2699},
abstract = {INTRODUCTION: We present a case of capsular block syndrome that occurred after intravitreal injection of ranibizumab in a patient with age-related macular degeneration, which has not been reported in the literature.<br><br>CASE PRESENTATION: A 78-year-old male presented with decreased visual acuity in the right eye. Slit-lamp examination findings were unremarkable; however, AMD was diagnosed based on fundus examination, fluorescein angiography, and optical coherence tomography (OCT). Subsequently, the patient was administered an intravitreal injection of ranibizumab. A slit-lamp examination revealed residual cortical material, numerous inflammatory cells, and posterior capsular distension 1 week after the injection. OCT showed an adhesion of the intraocular lens to the continuous curvilinear capsulorhexis site. The patient's vision improved following Nd:YAG laser posterior capsulotomy.<br><br>CONCLUSION: Meticulous cortical removal is crucial during phacoemulsification to prevent capsular block syndrome. In patients with a history of cataract surgery, verifying the absence of residual cortical material before administering an intravitreal injection of ranibizumab is important.},
}
@article {pmid38475838,
year = {2024},
author = {Saeedi-Maleki, Z and Javadzadeh, A and Brumandpur, F and Ghorbanihaghjo, A and Khanzadeh, S and Mousavi, F},
title = {Serum adropin level in wet-type age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {27},
pmid = {38475838},
issn = {2056-9920},
support = {Tabriz University of Medical Sciences//Tabriz University of Medical Sciences/ ; },
abstract = {PURPOSE: Our objective was to compare the serum Adropin levels between patients with wet-type Age-Related Macular Degeneration (AMD) and otherwise healthy individuals.<br><br>METHOD: The study included 45 patients with wet-type AMD and 45 individuals without age-related macular degeneration. Patients with co-morbidities such as diabetes, hypertension, autoimmune diseases, and a previous history of visual impairment; were excluded. FBS, Hemoglobin A1C (HbA1C), lipid profile, and serum Adropin level were checked.<br><br>RESULTS: The mean serum Adropin level of patients with wet-type AMD was significantly lower than the control group (P-value&#x2009;<&#x2009;0.001). Also, the mean High-sensitivity C-reactive protein (hsCRP) level and High Density Lipoprotein (HDL) were significantly higher in wet-type AMD patients (P-value&#x2009;=&#x2009;0.031 and <&#x2009;0.001 respectively).<br><br>CONCLUSIONS: In our study, wet-type AMD was associated with a lower level of serum Adropin. Because of Adropin involvement in glucose metabolism and age-related changes, it may have a role in the pathogenesis of AMD, but it requires more investigations at the molecular level to elucidate its function.},
}
@article {pmid38474284,
year = {2024},
author = {Fontaine, V and Boumedine, T and Monteiro, E and Fournié, M and Gersende, G and Sahel, JA and Picaud, S and Veillet, S and Lafont, R and Latil, M and Dilda, PJ and Camelo, S},
title = {RAR Inhibitors Display Photo-Protective and Anti-Inflammatory Effects in A2E Stimulated RPE Cells In Vitro through Non-Specific Modulation of PPAR or RXR Transactivation.},
journal = {International journal of molecular sciences},
volume = {25},
number = {5},
pages = {},
pmid = {38474284},
issn = {1422-0067},
support = {none : private funding and ANR-18-IAHU-01//Biophytis and Programme Investissements d'Avenir IHU FOReSIGHT./ ; },
mesh = {Anti-Inflammatory Agents ; *Carotenoids ; Drug Inverse Agonism ; Inflammation ; *Macular Degeneration/metabolism ; *para-Aminobenzoates ; *Peroxisome Proliferator-Activated Receptors/metabolism ; *Quinolines ; Retinoic Acid Receptor alpha/metabolism ; Retinoid X Receptors/metabolism ; Retinoids/metabolism ; Transcriptional Activation ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {N-retinylidene-N-retinylethanolamine (A2E) has been associated with age-related macular degeneration (AMD) physiopathology by inducing cell death, angiogenesis and inflammation in retinal pigmented epithelial (RPE) cells. It was previously thought that the A2E effects were solely mediated via the retinoic acid receptor (RAR)-α activation. However, this conclusion was based on experiments using the RAR "specific" antagonist RO-41-5253, which was found to also be a ligand and partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ. Moreover, we previously reported that inhibiting PPAR and retinoid X receptor (RXR) transactivation with norbixin also modulated inflammation and angiogenesis in RPE cells challenged in the presence of A2E. Here, using several RAR inhibitors, we deciphered the respective roles of RAR, PPAR and RXR transactivations in an in vitro model of AMD. We showed that BMS 195614 (a selective RAR-α antagonist) displayed photoprotective properties against toxic blue light exposure in the presence of A2E. BMS 195614 also significantly reduced the AP-1 transactivation and mRNA expression of the inflammatory interleukin (IL)-6 and vascular endothelial growth factor (VEGF) induced by A2E in RPE cells in vitro, suggesting a major role of RAR in these processes. Surprisingly, however, we showed that (1) Norbixin increased the RAR transactivation and (2) AGN 193109 (a high affinity pan-RAR antagonist) and BMS 493 (a pan-RAR inverse agonist), which are photoprotective against toxic blue light exposure in the presence of A2E, also inhibited PPARs transactivation and RXR transactivation, respectively. Therefore, in our in vitro model of AMD, several commercialized RAR inhibitors appear to be non-specific, and we propose that the phototoxicity and expression of IL-6 and VEGF induced by A2E in RPE cells operates through the activation of PPAR or RXR rather than by RAR transactivation.},
}
@article {pmid38474086,
year = {2024},
author = {Rajanala, K and Upadhyay, A},
title = {Epigenetic Switches in Retinal Homeostasis and Target for Drug Development.},
journal = {International journal of molecular sciences},
volume = {25},
number = {5},
pages = {},
pmid = {38474086},
issn = {1422-0067},
mesh = {*Epigenesis, Genetic ; *Retina/metabolism ; DNA Methylation ; Homeostasis ; Drug Development ; },
abstract = {Retinal homeostasis, a tightly regulated process maintaining the functional integrity of the retina, is vital for visual function. Emerging research has unveiled the critical role of epigenetic regulation in controlling gene expression patterns during retinal development, maintenance, and response to mutational loads and injuries. Epigenetic switches, including DNA methylation, histone modifications, and non-coding RNAs, play pivotal roles in orchestrating retinal gene expression and cellular responses through various intracellular, extracellular, and environmental modulators. This review compiles the current knowledge on epigenetic switches in retinal homeostasis, providing a deeper understanding of their impact on retinal structural integrity and function and using them as potential targets for therapeutic interventions.},
}
@article {pmid38472988,
year = {2024},
author = {Burchard, CV and Roider, J and Kepp, T},
title = {Analysis of OCT Scanning Parameters in AMD and RVO.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
pmid = {38472988},
issn = {2075-4418},
abstract = {Optical coherence tomography (OCT) is an extensively used imaging tool for disease monitoring in both age-related macular degeneration (AMD) and retinal vein occlusion (RVO). However, there is limited literature on minimum requirements of OCT settings for reliable biomarker detection. This study systematically investigates both the influence of scan size and interscan distance (ISD) on disease activity detection. We analyzed 80 OCT volumes of AMD patients and 12 OCT volumes of RVO patients for the presence of subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelium detachment (PED). All volume scans had a scan size of 6 × 6 mm and an ISD of 125 µm. We analyzed both general fluid distribution and how biomarker detection sensitivity decreases when reducing scan size or density. We found that in AMD patients, all fluids were nearly normally distributed, with most occurrences in the foveal center and concentric decrease towards the periphery. When reducing the scan size to 3 × 3 and 2 × 2 mm, disease activity detection was still high (0.98 and 0.96). Increasing ISD only slightly can already compromise biomarker detection sensitivity (0.9 for 250 µm ISD against 125 µm ISD).},
}
@article {pmid38472430,
year = {2024},
author = {Jonas, JB and Panda-Jonas, S and Jonas, RA},
title = {Drusen in the macula and parapapillary region.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {8},
pages = {2503-2513},
pmid = {38472430},
issn = {1435-702X},
mesh = {Humans ; Middle Aged ; Female ; Male ; *Retinal Pigment Epithelium/pathology ; *Macula Lutea/pathology ; *Retinal Drusen/diagnosis/etiology ; Bruch Membrane/pathology ; Aged ; Tomography, Optical Coherence/methods ; Uveal Neoplasms/pathology/diagnosis/complications ; Melanoma/diagnosis/pathology ; Optic Disk/pathology ; Eye Enucleation ; Adult ; Retrospective Studies ; Fluorescein Angiography/methods ; Glaucoma, Angle-Closure/diagnosis/surgery ; Optic Disk Drusen/diagnosis ; Aged, 80 and over ; Fundus Oculi ; Uveal Melanoma ; },
abstract = {PURPOSE: To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in the parapapillary region.<br><br>METHODS: We histomorphometrically examined human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma.<br><br>RESULTS: The study included 106 eyes (age, 62.6&#x2009;&#xb1;&#x2009;15.2&#xa0;years) with macular drusen (n&#x2009;=&#x2009;7 globes) or parapapillary drusen (n&#x2009;=&#x2009;29 eyes) and 70 eyes without drusen. In all drusen, periodic-acid-Schiff-positive material was located between the RPE basal membrane and the inner collagenous layer of Bruch's membrane (BM). Macular drusen as compared with parapapillary drusen had lower height (15.2&#x2009;&#xb1;&#x2009;10.1&#xa0;&#xb5;m versus 34.3&#x2009;&#xb1;&#x2009;19.8&#xa0;&#xb5;m; P&#x2009;=&#x2009;0.003), while both groups did not differ significantly in basal drusen width (74.0&#x2009;&#xb1;&#x2009;36.3&#xa0;&#xb5;m versus 108.7&#x2009;&#xb1;&#x2009;101.0&#xa0;&#xb5;m; P&#x2009;=&#x2009;0.95). Eyes with macular drusen and eyes without drusen did not differ significantly in BM thickness (2.74&#x2009;&#xb1;&#x2009;0.44&#xa0;&#xb5;m versus 2.55&#x2009;&#xb1;&#x2009;0.88&#xa0;&#xb5;m; P&#x2009;=&#x2009;0.57) or in RPE cell density (35.4&#x2009;&#xb1;&#x2009;10.4 cells/480&#xa0;&#xb5;m versus 32.8&#x2009;&#xb1;&#x2009;7.5 cells/480&#xa0;&#xb5;m; P&#x2009;=&#x2009;0.53), neither in the drusen region nor in the drusen vicinity, while BM thickness (4.60&#x2009;&#xb1;&#x2009;1.490&#xa0;&#xb5;m; P&#x2009;<&#x2009;0.001) and RPE cell density (56.9&#x2009;&#xb1;&#x2009;26.8 cells/480&#xa0;&#xb5;m; P&#x2009;=&#x2009;0.005) were higher at the parapapillary drusen. Eyes with macular drusen, eyes with parapapillary drusen, and eyes without drusen did not differ significantly in choriocapillaris density (all P&#x2009;>&#x2009;0.10) and thickness (all P&#x2009;>&#x2009;0.35). Limitations of the study, among others, were a small number and size of drusen examined, diseases leading to enucleation, lack of serial sections, limited resolution of light microscopy, and enucleation-related and histological preparation-associated artefacts.<br><br>CONCLUSIONS: The findings of this study, also taking into account its methodological limitations, suggest that macular drusen and parapapillary drusen shared the morphological feature of periodic-acid-Schiff-positive material between the RPE basal membrane and BM and that they did not vary significantly in choriocapillaris thickness and density. RPE cell density and BM thickness were higher in parapapillary drusen than in macular drusen.},
}
@article {pmid38472377,
year = {2024},
author = {Yanık, &#xd6; and Demirel, S and Özcan, G and Batıoğlu, F and Özmert, E},
title = {Qualitative and quantitative comparisons of type 1 macular neovascularizations between pachychoroid neovasculopathy and neovascular age-related macular degeneration using optical coherence tomography angiography.},
journal = {Eye (London, England)},
volume = {38},
number = {9},
pages = {1714-1721},
pmid = {38472377},
issn = {1476-5454},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Middle Aged ; *Fluorescein Angiography/methods ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Choroidal Neovascularization/diagnostic imaging/diagnosis ; Visual Acuity/physiology ; Retinal Vessels/diagnostic imaging/pathology ; Retrospective Studies ; Choroid/blood supply/diagnostic imaging ; Aged, 80 and over ; },
abstract = {OBJECTIVES: To compare qualitative and quantitative features of type 1 macular neovascularizations (MNV) in pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Forty-three treatment-naive eyes of 41 PNV patients and 40 treatment-naive eyes of 38 patients with nAMD were included. The patients were classified as PNV or nAMD according to the presence of pachychoroid features and soft/reticular drusen. Presence of central trunk and maturity of the MNV were evaluated on optical coherence tomography angiography (OCTA) images. MNV area, vessel density (VD), total vessel length (VL), number of intersection points (IPs), fractal dimension (FD), and lacunarity (LAC) were calculated using ImageJ software and FracLac plugin.<br><br>RESULTS: The mean age was 56.8&#x2009;&#xb1;&#x2009;8.7 years in PNV and 70.4&#x2009;&#xb1;&#x2009;8.8 years in neovascular AMD groups (p&#x2009;<&#x2009;0.001). Compared to nAMD, the presence of central trunk was less frequent in PNV (48.8% vs 77.5%, p&#x2009;=&#x2009;0.007). Immature MNV pattern was observed more frequently in PNV eyes than nAMD (41.9% vs 20.0%, p&#x2009;=&#x2009;0.009). PNV cases had significantly lower median MNV area [0.913(1.115) vs 2.542(3.273) mm&#xb2;], total VL [14.84 (20.46) vs 36.34 (44.68) mm], number of IPs [104(140) vs 335(417.3)], and FD [1.56(0.10) vs 1.59(0.11)] comparing to nAMD cases (p&#x2009;<&#x2009;0.001, p&#x2009;=&#x2009;0.001, p&#x2009;<&#x2009;0.001, p&#x2009;=&#x2009;0.043 respectively). However, the mean VD (42.4&#x2009;&#xb1;&#x2009;6.8 vs 42.9&#x2009;&#xb1;&#x2009;9.0%) and the median LAC values [0.42 (0.09) vs 0.42 (0.09)] did not differ significantly between groups (p&#x2009;=&#x2009;0.776, p&#x2009;=&#x2009;0.526, respectively).<br><br>CONCLUSION: Morphological and quantitative differences exist in type 1 neovascular lesions. Type 1 MNVs in the PNV group are characterized by a smaller and less complex structure.},
}
@article {pmid38471273,
year = {2024},
author = {Wang, Y and Liu, X and Wang, B and Sun, H and Ren, Y and Zhang, H},
title = {Compounding engineered mesenchymal stem cell-derived exosomes: A potential rescue strategy for retinal degeneration.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {173},
number = {},
pages = {116424},
doi = {10.1016/j.biopha.2024.116424},
pmid = {38471273},
issn = {1950-6007},
mesh = {Humans ; Aged ; *Exosomes/metabolism ; *Retinal Degeneration/therapy/metabolism ; *MicroRNAs/genetics/metabolism ; Cytokines/metabolism ; *Mesenchymal Stem Cells/metabolism ; },
abstract = {The prevalence of retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, has been increasing globally and is linked to the aging population and improved life expectancy. These diseases are characterized by chronic, progressive neuronal damage or depletion of the photoreceptor cells in the retina, and limited effective treatment options are currently available. Mesenchymal stem cell-derived exosomes (MSC-EXOs) containing cytokines, growth factors, lipids, mRNA, and miRNA, which act as mediators of intercellular communication transferring bioactive molecules to recipient cells, offer an appealing, non-cellular nanotherapeutic approach for retinal degenerative diseases. However, treatment specificity is compromised due to their high heterogeneity in size, content, functional effects, and parental cellular source. To improve this, engineered MSC-EXOs with increased drug-loading capacity, targeting ability, and resistance to bodily degradation and elimination have been developed. This review summarizes the recent advances in miRNAs of MSC-EXOs as a treatment for retinal degeneration, discussing the strategies and methods for engineering therapeutic MSC-EXOs. Notably, to address the single functional role of engineered MSC-EXOs, we propose a novel concept called "Compound Engineered MSC-EXOs (Co-E-MSC-EXOs)" along with its derived potential therapeutic approaches. The advantages and challenges of employing Co-E-MSC-EXOs for retinal degeneration in clinical applications, as well as the strategies and issues related to them, are also highlighted.},
}
@article {pmid38471039,
year = {2024},
author = {Fragiotta, S and Dysli, C and Parravano, M and Sacconi, R and Fantaguzzi, F and Servillo, A and Severo, AA and Tombolini, B and Costanzo, E and De Geronimo, D and Capuano, V and Souied, E and Bandello, F and Querques, G},
title = {PHENOTYPIC CHARACTERIZATION OF PREDICTORS FOR DEVELOPMENT AND PROGRESSION OF GEOGRAPHIC ATROPHY USING OPTICAL COHERENCE TOMOGRAPHY.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {7},
pages = {1232-1241},
doi = {10.1097/IAE.0000000000004090},
pmid = {38471039},
issn = {1539-2864},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/diagnosis ; Retrospective Studies ; Male ; Female ; *Disease Progression ; Aged ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Phenotype ; *Fluorescein Angiography/methods ; Aged, 80 and over ; Follow-Up Studies ; Visual Acuity ; Fundus Oculi ; Middle Aged ; Bruch Membrane/pathology/diagnostic imaging ; },
abstract = {PURPOSE: To evaluate the impact of optical coherence tomography phenotypes preceding atrophy related to age-related macular degeneration on the progression of atrophic lesions.<br><br>METHODS: In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate age-related macular degeneration with a minimum follow-up of 24 months were included. The atrophy was quantified using fundus autofluorescence, also considering the directionality of atrophy as centrifugal and centripetal progression rates. The main outcome measures were geographic atrophy (GA) progression rate (mm 2 /year) and square root transformation of GA (mm 2 /year).<br><br>RESULTS: The best-fit model for GA (odds ratio: 1.81, P < 0.001) and square root transformation of GA (odds ratio: 1.36, P < 0.001) areas revealed that the main baseline predictor was the presence of a retinal pigment epithelium-basal lamina-Bruch membrane splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (odds ratio: 0.52, P < 0.001) when considered with other confounders.<br><br>CONCLUSION: A thin retinal pigment epithelium-basal lamina-Bruch membrane splitting without evidence of neovascularization on optical coherence tomography angiography likely represents an optical coherence tomography signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.},
}
@article {pmid38470327,
year = {2024},
author = {Borrelli, E and Barresi, C and Ricardi, F and Berni, A and Grosso, D and Viggiano, P and Marolo, P and Introini, U and Reibaldi, M and Bandello, F},
title = {Distinct Pathways of Macular Atrophy in Type 3 Macular Neovascularization Associated With AMD.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {3},
pages = {18},
pmid = {38470327},
issn = {1552-5783},
mesh = {Humans ; *Macular Degeneration/complications/diagnosis ; Eye ; Neovascularization, Pathologic ; *Retinal Detachment ; Atrophy ; },
abstract = {PURPOSE: To explore the occurrence of macular atrophy (MA) in eyes with age-related macular degeneration (AMD)-associated Type 3 macular neovascularization (MNV) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Importantly, we aimed at describing the existence of separate pathways leading to MA.<br><br>METHODS: We analyzed 41 participants (41 eyes) with treatment-na&#xef;ve Type 3 MNV who were followed up for a duration of 12&#xa0;months after beginning the anti-VEGF therapy. At the one-year follow-up visit, optical coherence tomography (OCT) scans were reviewed for the presence of MA. MA regions of interest (ROIs) were selected and traced back to their original dominant baseline lesion (i.e., precursor) through previous serially captured OCT scans. Baseline lesions included precursors associated with the development and exudation of MNV and causes external to the neovascularization itself.<br><br>RESULTS: At the one-year follow-up visit, MA was graded to be present in 38 (92.7%) out of 41 eyes. These 78 MA ROIs were divided into two subgroups according to the precursor lesion, yielding a group of 53 MA lesions with precursors associated with the development and exudation of MNV (i.e., MA caused by physical harm from Type 3 neovessels, collapse of a serous pigment epithelium detachment, and fibrosis) and 25 MA regions with precursors external to the neovascularization itself (i.e., MA caused by drusen or subretinal drusenoid deposits).<br><br>CONCLUSIONS: Eyes with Type 3 MNV are commonly complicated by MA and precursors of MA include causes associated with the development and exudation of MNV, as well as lesions unrelated to the neovascularization process itself.},
}
@article {pmid38469204,
year = {2024},
author = {Au Eong, JTW and Tsai, JHJ and Au Eong, KG},
title = {Severe astigmatism secondary to large intraocular lens pantoscopic tilt because of a malpositioned haptic following cataract surgery.},
journal = {Journal of surgical case reports},
volume = {2024},
number = {3},
pages = {rjae134},
pmid = {38469204},
issn = {2042-8812},
abstract = {An 80-year-old woman presented with painless blurring of vision and monocular diplopia in her left eye following routine phacoemulsification and monofocal intraocular lens (IOL) implantation 5 weeks earlier. Her uncorrected visual acuity (VA) was 6/60 correctable with pinhole to 6/21. Her best-corrected VA was 6/15 with a subjective refraction of -0.50DS/-5.25DCx37. Her corneal astigmatism was -1.25DCx74. Ophthalmic examination disclosed a severely tilted single-piece posterior chamber IOL in the capsular bag. The inferior portion of the optic was tilted posteriorly because of a twisted and malpositioned haptic. The patient underwent remedial surgery to untwist and reposition the IOL haptic which led to immediate improvement of the IOL position. Her uncorrected VA improved to 6/12[-2] correctable with pinhole to 12[+1] with an autorefraction of +0.25DS/-2.00DCx74 on the first postoperative day. One month postoperatively, her best-corrected VA was 6/12 with a refraction of +0.50DS/-2.50DCx82. Her final vision was limited by myopic macular degeneration.},
}
@article {pmid38467968,
year = {2024},
author = {Gurubaran, IS},
title = {Mitochondrial damage and clearance in retinal pigment epithelial cells.},
journal = {Acta ophthalmologica},
volume = {102 Suppl 282},
number = {},
pages = {3-53},
doi = {10.1111/aos.16661},
pmid = {38467968},
issn = {1755-3768},
mesh = {Humans ; Animals ; Mice ; Infant ; Inflammasomes/metabolism ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; Retinal Pigment Epithelium ; Thrombin ; Proteasome Endopeptidase Complex/metabolism/pharmacology ; Quality of Life ; *Macular Degeneration/genetics/metabolism ; Oxidative Stress ; *Geographic Atrophy ; Biomarkers/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism/pharmacology ; },
abstract = {Age-related macular degeneration (AMD) is a devastating eye disease that causes permanent vision loss in the central part of the retina, known as the macula. Patients with such severe visual loss face a reduced quality of life and are at a 1.5 times greater risk of death compared to the general population. Currently, there is no cure for or effective treatment for dry AMD. There are several mechanisms thought to underlie the disease, for example, ageing-associated chronic oxidative stress, mitochondrial damage, harmful protein aggregation and inflammation. As a way of gaining a better understanding of the molecular mechanisms behind AMD and thus developing new therapies, we have created a peroxisome proliferator-activated receptor gamma coactivator 1-alpha and nuclear factor erythroid 2-related factor 2 (PGC1α/NFE2L2) double-knockout (dKO) mouse model that mimics many of the clinical features of dry AMD, including elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in retinal pigment epithelial cells (RPE). In addition, a human RPE cell-based model was established to examine the impact of non-functional intracellular clearance systems on inflammasome activation. In this study, we found that there was a disturbance in the autolysosomal machinery responsible for clearing mitochondria in the RPE cells of one-year-old PGC1α/NFE2L2-deficient mice. The confocal immunohistochemical analysis revealed an increase in autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as multiple mitophagy markers such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN), along with signs of damaged mitochondria. However, no increase in autolysosome formation was detected, nor was there a colocalization of the lysosomal marker LAMP2 or the mitochondrial marker, ATP synthase β. There was an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells, together with autofluorescent aggregates. Additionally, we observed an increase in the numbers of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in PGC1α/NFE2L2 dKO retinal specimens compared to wild-type animals. There was a trend towards increased complement component C5a and increased involvement of the serine protease enzyme, thrombin, in enhancing the terminal pathway producing C5a, independent of C3. The levels of primary acute phase C-reactive protein and receptor for advanced glycation end products were also increased in the PGC1α/NFE2L2 dKO retina. Furthermore, selective proteasome inhibition with epoxomicin promoted both nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondrial-mediated oxidative stress, leading to the release of mitochondrial DNA to the cytosol, resulting in potassium efflux-dependent activation of the absent in melanoma 2 (AIM2) inflammasome and the subsequent secretion of interleukin-1β in ARPE-19 cells. In conclusion, the data suggest that there is at least a relative decrease in mitophagy, increases in the amounts of C5 and thrombin and decreased C3 levels in this dry AMD-like model. Moreover, selective proteasome inhibition evoked mitochondrial damage and AIM2 inflammasome activation in ARPE-19 cells.},
}
@article {pmid38466965,
year = {2024},
author = {Singh, RP and Avery, RL and Barakat, MR and Kim, JE and Kiss, S},
title = {Evidence-Based Use of Bevacizumab in the Management of Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {3},
pages = {156-162},
doi = {10.3928/23258160-20240108-01},
pmid = {38466965},
issn = {2325-8179},
mesh = {Humans ; Bevacizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use/pharmacology ; Injections ; *Macular Degeneration/drug therapy ; *Retinal Diseases/drug therapy ; Intravitreal Injections ; },
abstract = {Indicated for colorectal cancer for decades, bevacizumab has been widely used off label to treat retinal diseases, and the benefits of its use, specifically in neovascular age-related macular degeneration, have been demonstrated in multiple clinical trials. The intravitreal delivery of bevacizumab requires it to be aseptically repackaged into individual syringes by compounding pharmacies for use in the eye. Although the repackaging process is permitted by the US Food and Drug Administration, the resultant product does not meet the specific standards of products approved for use as ophthalmic injectables nor is the parenteral innovator solution compliant with ophthalmic standards. Studies have also demonstrated variability in the quality and quantity of repackaged bevacizumab. This narrative review summarizes the evidence and discusses the role of off-label bevacizumab in the treatment and management of retinal diseases, its mechanism of action, current challenges and provides a critical appraisal of current evidence, clinical implications, and future directions. [Ophthalmic Surg Lasers Imaging Retina 2024;55:155-162.].},
}
@article {pmid38466525,
year = {2024},
author = {Voichanski, S and Weinshtein, N and Hanhart, J},
title = {Relative yield of retinal imaging versus clinical exam in following neovascular exudative age related macular degeneration.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {126},
pmid = {38466525},
issn = {1573-2630},
mesh = {Male ; Humans ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Tomography, Optical Coherence/methods ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To compare therapeutic decisions between 3 diagnostic protocols and to assess the need for in-person physical doctor-patient encounter in follow up and treatment of neovascular exudative age-related macular degeneration (AMD).<br><br>METHODS: Analysis of 88 eyes of 88 unique patients with neovascular AMD who were routinely followed at our medical retina clinic. A retinal specialist reviewed all images in advance and wrote his decisions. He later attended an in-person encounters with all patients and documented his decisions. Masking was done by not exposing any identifying information to the specialist and by randomizing patient's images order before the in-person encounter. Therapeutic decisions regarding intravitreal injections intervals and agent selection were made based on three protocols: (1) optic coherence tomography (OCT); (2) OCT/Ultra-widefield (UWF) color image; (3) OCT/UWF/full clinical exam. Visual acuity (VA) was incorporated into all protocols.<br><br>RESULTS: We found an agreement of 93% between those protocols regarding the intervals of injections, and of 100% regarding injection agent selection. When comparing OCT, OCT/UWF and OCT/UWF/clinical exam guided decision making, there were no discrepancies between OCT and OCT/UWF. There were 6 out of 88 discrepancies (7%) between OCT/UWF and OCT/UWF/clinical exam. Of those 6 discrepancies, all were regarding intervals (Bland-Altman bias&#x2009;=&#x2009;-&#x2009;0.2386). All discrepancies between OCT/UWF and OCT/UWF/Clinical exam were due to patients' preferences, socioeconomic issues and fellow eye considerations, addressed during the face-to-face encounter with patients. Physical examination itself did not affect decision making.<br><br>CONCLUSIONS: Neovascular exudative AMD follow up and treatment decisions can be guided by VA and OCT, with UWF adding important information regarding macula and peripheral retina, but rarely affecting decision making. However, decision making may also be driven by patients' preferences and other considerations that are being made only during the face-to-face visit and discussion. Thus, every approach supporting imaging only decision making, must take these factors into account.},
}
@article {pmid38466281,
year = {2024},
author = {Curcio, CA and Kar, D and Owsley, C and Sloan, KR and Ach, T},
title = {Age-Related Macular Degeneration, a Mathematically Tractable Disease.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {3},
pages = {4},
pmid = {38466281},
issn = {1552-5783},
mesh = {Humans ; Adult ; Aged ; *Macular Degeneration ; Retina ; *Macula Lutea ; *Geographic Atrophy ; Retinal Cone Photoreceptor Cells ; },
abstract = {A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.},
}
@article {pmid38462944,
year = {2024},
author = {Furino, C and Albano, V and D'Addario, M and Reibaldi, M and Boscia, F and Alessio, G},
title = {Brolucizumab effectiveness in pigment epithelium detachment due to exudative AMD in naïve treatment or non-responder patients.},
journal = {European journal of ophthalmology},
volume = {34},
number = {6},
pages = {2025-2031},
doi = {10.1177/11206721241238391},
pmid = {38462944},
issn = {1724-6016},
mesh = {Humans ; Retrospective Studies ; *Intravitreal Injections ; Male ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Visual Acuity/physiology ; *Retinal Detachment/drug therapy/physiopathology/diagnosis ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged ; *Tomography, Optical Coherence ; *Retinal Pigment Epithelium/pathology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Fluorescein Angiography ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Treatment Outcome ; Aged, 80 and over ; Follow-Up Studies ; },
abstract = {PURPOSE: To investigate outcomes after Brolucizumab injection in naïve treatment or non-responder patients with exudative age-related macular degeneration (AMD).<br><br>METHODS: It is a retrospective, comparative, cohort study conducted at the tertiary referral center of the University Hospital Polyclinic of Bari, for 5 years, from November 2017 until May 2022. 41 eyes with wet-AMD (w-AMD) were included, undergoing anti-vascular endothelial growth factor (VEGF) intravitreal injections. The sample was divided into two groups, the Bro-Switch group, and the Bro-Na&#xef;ve group. The Bro-Switch group previously received a slot of other anti-VEGF intravitreal drugs. The Bro-Na&#xef;ve group received Brolucizumab (Bro) as the first treatment. The pigment epithelium detachment (PED) and the best-corrected visual acuity (BCVA) outcomes before and after Bro-injection were evaluated.<br><br>RESULTS: A significant reduction in PED measurement was registered in all eyes treated with Bro-injection (p&#x2009;=&#x2009;0.35). The Bro-Na&#xef;ve group improved better in PED measurement (mean difference: 297.92&#x2009;&#xb1;&#x2009;72,32) as compared to the Bro-Switch group (mean difference: 185.06&#x2009;&#xb1;&#x2009;11.07). On the contrary, no significant reduction in BCVA in the two groups was recorded (p&#x2009;=&#x2009;0.66).<br><br>CONCLUSION: We suggest Bro-injection for w-AMD as effective anatomical outcomes in PED flattening, but not similar in visual results. Although this study evaluated short-term outcomes, the hopeful results can lead to interesting medium-long time effects.},
}
@article {pmid38462646,
year = {2024},
author = {Jung, J and Han, J and Han, JM and Ko, J and Yoon, J and Hwang, JS and Park, JI and Hwang, G and Jung, JH and Hwang, DD},
title = {Prediction of neovascular age-related macular degeneration recurrence using optical coherence tomography images with a deep neural network.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {5854},
pmid = {38462646},
issn = {2045-2322},
support = {2023R1A2C2007625//National Research Foundation of Korea/ ; 2022R1F1A1074063//National Research Foundation of Korea/ ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; Artificial Intelligence ; Retrospective Studies ; Neural Networks, Computer ; *Macular Degeneration/diagnostic imaging ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/diagnostic imaging/drug therapy ; Ranibizumab ; },
abstract = {Neovascular age-related macular degeneration (nAMD) can result in blindness if left untreated, and patients often require repeated anti-vascular endothelial growth factor injections. Although, the treat-and-extend method is becoming popular to reduce vision loss attributed to recurrence, it may pose a risk of overtreatment. This study aimed to develop a deep learning model based on DenseNet201 to predict nAMD recurrence within 3 months after confirming dry-up 1 month following three loading injections in treatment-naïve patients. A dataset of 1076 spectral domain optical coherence tomography (OCT) images from 269 patients diagnosed with nAMD was used. The performance of the model was compared with that of 6 ophthalmologists, using 100 randomly selected samples. The DenseNet201-based model achieved 53.0% accuracy in predicting nAMD recurrence using a single pre-injection image and 60.2% accuracy after viewing all the images immediately after the 1st, 2nd, and 3rd injections. The model outperformed experienced ophthalmologists, with an average accuracy of 52.17% using a single pre-injection image and 53.3% after examining four images before and after three loading injections. In conclusion, the artificial intelligence model demonstrated a promising ability to predict nAMD recurrence using OCT images and outperformed experienced ophthalmologists. These findings suggest that deep learning models can assist in nAMD recurrence prediction, thus improving patient outcomes and optimizing treatment strategies.},
}
@article {pmid38462368,
year = {2024},
author = {Dai, H and Lu, YY and Zhao, J},
title = {[Challenges and strategies in the treatment of neovascular age-related macular degeneration].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {60},
number = {3},
pages = {215-219},
doi = {10.3760/cma.j.cn112142-20230807-00026},
pmid = {38462368},
issn = {0412-4081},
support = {CFH 2020-2-4051//Capital's Funds for Health Improvement and Research/ ; },
mesh = {Humans ; Aged ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; *Macular Degeneration/therapy ; Visual Acuity ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Treatment Outcome ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in the elderly, and anti-vascular endothelial growth factor (VEGF) therapy is currently the primary treatment approach. However, the real-world effectiveness of nAMD treatment is not always satisfactory and faces various challenges. Frequent administration and follow-up burdens can lead to decreased patient compliance during long-term treatment, resulting in suboptimal outcomes. Some lesions exhibit poor or no response to anti-VEGF treatment, leading to difficulties in maintaining or even declining visual acuity. Factors such as lesion fibrosis and tissue atrophy can contribute to visual deterioration. Therefore, standardizing and individualizing treatment plans, along with enhancing comprehensive monitoring and management throughout the disease course, are crucial improvement measures. The evidence-based guidelines for diagnosis and treatment of age-related macular degeneration in China, released in 2023, provide guidance for standardized clinical diagnosis and treatment. Meanwhile, research and development of new drugs and administration methods are anticipated for the future.},
}
@article {pmid38461947,
year = {2024},
author = {Baek, J and Ashrafkhorasani, M and Mahmoudi, A and Nittala, MG and Corradetti, G and Sadda, SR},
title = {En Face and Volumetric Comparison of Hypertransmission Defects Evaluated by Cirrus and Spectralis Optical Coherence Tomography.},
journal = {American journal of ophthalmology},
volume = {264},
number = {},
pages = {135-144},
doi = {10.1016/j.ajo.2024.03.003},
pmid = {38461947},
issn = {1879-1891},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Imaging, Three-Dimensional ; Female ; Male ; Aged ; Geographic Atrophy/diagnosis ; Aged, 80 and over ; Visual Acuity/physiology ; Middle Aged ; },
abstract = {PURPOSE: To evaluate and compare en face and 3-dimensional (3-D) properties of hypertransmission defects (HTDs) between different optical coherence tomography (OCT) devices using OCT volumes and reconstructed en face images.<br><br>SETTINGS: Comparative diagnostic evaluation study.<br><br>METHODS: Thirty eyes with dry age-related macular degeneration (AMD) that underwent dense OCT macular volume scans with both the Spectralis (97 B-scans/volume; 2910 B-scans in total) and Cirrus OCT (128 B-scans/volume; 3840 B-scans in total) from the Amish Eye Study cohort were included in this analysis. HTD regions were labeled on each B-scan and reconstructed into en face and 3-D volume images. Properties of HTD volume were compared between the 2 devices.<br><br>RESULTS: The qualitative score of en face images for HTD was higher for the Cirrus compared to the Spectralis (P < .01). The quality of Spectralis en face images improved after preprocessing and reconstruction. The 2-D HTD area on en face obtained from 2-D projections of 3-D volume did not differ between devices (P = .478, ICC = 0.998; Jaccard index 0.721 &#xb1; 0.086). There was no difference in the number, volume, PALs, and surface areas of HTDs between devices in the volumetric analysis (all P &#x2265; .090). The signal intensity of HTD normalized by the mean choroidal signal intensity did not differ between devices (P = .861).<br><br>CONCLUSIONS: The visualization of HTD on en face images from Spectralis OCT could be enhanced through image processing. The equivalence in 3-D HTD parameters between the 2 devices suggests interchangeability for assessing these lesions in AMD.},
}
@article {pmid38461944,
year = {2024},
author = {Lee, AY and Kovacs, K and Orlin, A and Kiss, S and D'Amico, DJ and Segal, KL and Lelli, GJ and Godfrey, KJ},
title = {Incidence of Blepharoptosis Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.},
journal = {American journal of ophthalmology},
volume = {265},
number = {},
pages = {236-240},
pmid = {38461944},
issn = {1879-1891},
support = {UL1 TR002384/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Blepharoptosis/chemically induced/epidemiology ; *Intravitreal Injections/adverse effects ; Incidence ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Male ; Female ; Aged ; *Ranibizumab/adverse effects/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/epidemiology ; Aged, 80 and over ; Bevacizumab/adverse effects/administration &amp; dosage ; Middle Aged ; Antibodies, Monoclonal, Humanized/adverse effects/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; },
abstract = {PURPOSE: To determine the incidence of blepharoptosis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum.<br><br>DESIGN: Retrospective cohort study.<br><br>METHODS: International Classification of Diseases, Tenth Revision (ICD-10), codes were used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis after intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as controls. The outcomes were the incidence of ptosis in the injection group compared to the noninjection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without a speculum.<br><br>RESULTS: We recruited 1100 exudative AMD patients who received at least 1 intravitreal anti-VEGF injection and 2258 nonexudative AMD patients who had not received an injection. In the injection group, 18 of 1100 patients (1.6%) developed ptosis, compared with 52 of 2258 patients (2.3%) in the noninjection group (P = .25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months after the initial injection, and after more than a 1-year injection-free period. Eleven of 537 patients (2.0%) injected without a speculum developed ptosis, compared with 8 of 444 patients (1.8%) injected with a speculum (P = .82).<br><br>CONCLUSIONS: No statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis.},
}
@article {pmid38461841,
year = {2024},
author = {Lanzetta, P and Korobelnik, JF and Heier, JS and Leal, S and Holz, FG and Clark, WL and Eichenbaum, D and Iida, T and Xiaodong, S and Berliner, AJ and Schulze, A and Schmelter, T and Schmidt-Ott, U and Zhang, X and Vitti, R and Chu, KW and Reed, K and Rao, R and Bhore, R and Cheng, Y and Sun, W and Hirshberg, B and Yancopoulos, GD and Wong, TY and , },
title = {Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.},
journal = {Lancet (London, England)},
volume = {403},
number = {10432},
pages = {1141-1152},
doi = {10.1016/S0140-6736(24)00063-1},
pmid = {38461841},
issn = {1474-547X},
mesh = {Adult ; Humans ; *Angiogenesis Inhibitors/adverse effects ; DEAE-Dextran ; *Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/adverse effects ; Treatment Outcome ; },
abstract = {BACKGROUND: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg.<br><br>METHODS: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing.<br><br>FINDINGS: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6&#xb7;7 [SD 12&#xb7;6] and +6&#xb7;2 [11&#xb7;7] vs +7&#xb7;6 [12&#xb7;2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0&#xb7;97 (95% CI -2&#xb7;87 to 0&#xb7;92) and -1&#xb7;14 (-2&#xb7;97 to 0&#xb7;69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%]).<br><br>INTERPRETATION: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD.<br><br>FUNDING: Bayer AG and Regeneron Pharmaceuticals.},
}
@article {pmid38461839,
year = {2024},
author = {Chew, EY},
title = {Increasing concentrations of intravitreal therapies for neovascular age-related macular degeneration.},
journal = {Lancet (London, England)},
volume = {403},
number = {10432},
pages = {1110-1111},
doi = {10.1016/S0140-6736(24)00229-0},
pmid = {38461839},
issn = {1474-547X},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/drug therapy ; Tomography, Optical Coherence ; Retrospective Studies ; },
}
@article {pmid38460964,
year = {2024},
author = {Bellis, RM and Fei, Y and Le, B and Ledesma-Gil, G and Otero-Marquez, O and Tong, Y and Tai, K and Rosen, RB and Lema, GMC and Smith, RT},
title = {Correlation between ellipsoid zone thickness and the presence of subretinal drusenoid deposits in age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {38460964},
issn = {2397-3269},
mesh = {Humans ; Female ; Male ; *Retinal Drusen/diagnostic imaging ; Cross-Sectional Studies ; *Macular Degeneration/diagnostic imaging ; Retina ; Tomography, Optical Coherence/methods ; Dapsone/*analogs &amp; derivatives ; },
abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage.<br><br>METHODS: Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51-100; 61%&#x2009;women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000&#x2009;&#xb5;m nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction.<br><br>RESULTS: The mean EZ thickness differences between the SDD+D&#x2009;and drusen-only groups were (in &#x3bc;m) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p&#x2264;0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p&#x2264;0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age.<br><br>CONCLUSION: Subjects with SDDs (&#xb1;drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.},
}
@article {pmid38456089,
year = {2024},
author = {Hussain, SM and Robb, C and Tonkin, AM and Lacaze, P and Chong, TT and Beilin, LJ and Yu, C and Watts, GF and Ryan, J and Ernst, ME and Zhou, Z and Neumann, JT and McNeil, JJ},
title = {Association of plasma high-density lipoprotein cholesterol level with risk of incident dementia: a cohort study of healthy older adults.},
journal = {The Lancet regional health. Western Pacific},
volume = {43},
number = {},
pages = {100963},
pmid = {38456089},
issn = {2666-6065},
support = {P30 AG024824/AG/NIA NIH HHS/United States ; U01 AG029824/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: Recent studies have reported associations between high plasma high-density lipoprotein cholesterol (HDL-C) levels and risk of all-cause mortality, age-related macular degeneration, sepsis and fractures, but associations with dementia risk remain unclear. To determine whether high plasma HDL-C levels are associated with increased incident dementia risk in initially-healthy older people.<br><br>METHODS: We conducted a post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial; a double-blind, randomized, placebo-controlled trial of daily low-dose aspirin in healthy older people. ASPREE recruited 16,703 participants aged &#x2265;70 years (from Australia) and 2411 participants aged &#x2265;65 years (from the US) between 2010 and 2014. Participants had no diagnosed cardiovascular disease, dementia, physical disability, or life-threatening illness at enrolment and were cognitively healthy (3MS score &#x2265;78). All-cause dementia was a primary trial endpoint, and determined by DSM-IV criteria. Cox regression was used to examine hazard ratios between HDL-C categories <40&#xa0;mg/dL, 40-60&#xa0;mg/dL (reference category), 60-80&#xa0;mg/dL, and >80&#xa0;mg/dL and dementia. Restricted cubic spline curves were used to determine nonlinear associations. Data analysis was performed from October 2022 to January 2023.<br><br>FINDINGS: Of the 18,668 participants, 850 (4.6%) cases of incident dementia were recorded over 6.3 (SD 1.8) years. Participants with high HDL-C (>80&#xa0;mg/dL) had a 27% higher risk of dementia (HR 1.27, 95% CI 1.03, 1.58). Age stratified analyses demonstrated that the risk of incident dementia was higher in participants &#x2265;75 years compared to participants <75 years (HR 1.42, 95% CI 1.10, 1.83 vs HR 1.02, 95% CI 0.68, 1.51). Associations remained significant after adjusting for covariates including age, sex, country of enrolment, daily exercise, education, alcohol consumption, weight change over time, non-HDL-C, HDL-C-PRS, and APOE genotype.<br><br>INTERPRETATION: In a population of initially-healthy older adults aged &#x2265;75 years, high HDL-C levels were associated with increased risk of all-cause dementia.<br><br>FUNDING: National Institutes of Health, USA; National Health and Medical Research Council Australia; Monash University (Melbourne, VIC, Australia); and the Victorian Cancer Agency (Australia).},
}
@article {pmid38454852,
year = {2024},
author = {Zhao, C and Ding, Q and Yang, Z},
title = {Burdens and trends of blindness and vision loss among those aged 55 years and older: A systematic analysis for the Global Burden of Disease Study 2019.},
journal = {European journal of ophthalmology},
volume = {34},
number = {6},
pages = {1852-1864},
doi = {10.1177/11206721241238878},
pmid = {38454852},
issn = {1724-6016},
mesh = {Humans ; *Blindness/epidemiology ; Female ; Aged ; Male ; Middle Aged ; Prevalence ; *Global Burden of Disease/trends ; *Quality-Adjusted Life Years ; Aged, 80 and over ; Age Distribution ; Global Health ; Disability-Adjusted Life Years/trends ; Sex Distribution ; Vision, Low/epidemiology ; Cost of Illness ; Persons with Visual Disabilities/statistics &amp; numerical data ; },
abstract = {PURPOSE: To systematically analysis the burden and trends of blindness and vision loss for those aged ≥55 years from 1990 to 2019 and to predict trends over the next few years.<br><br>METHODS: The data were extracted from the Global Burden of Disease Study (GBD) 2019. Trends from 1990 to 2019 were calculated using average annual percentage change (AAPC) by joinpoint regression analysis. Bayesian age-period-cohort (BAPC) models were used to predict future trends.<br><br>RESULTS: In 2019, the global prevalence of blindness and vision loss was 471.1 million with 15.9 million disability-adjusted life-years (DALYs) for those aged &#x2265;55 years. These numbers will reach 640.3 million cases and 18.9 million DALYs in 2030. The prevalence rate (per 100,000 population) increased from 32,137.8 (95% uncertainty interval [UI], 26,307.9-39,246.3) in 1990 to 33,509 (95% UI, 27,435.5-40,996.2) in 2019, with an AAPC of 0.143 (95% confidence interval [CI], 0.125-0.161; P&#x2009;<&#x2009;0.001). The DALY rate (per 100,000 population) decreased from 632.9 (95% UI, 447.7-870.9) in 1990 to 579.3 (95% UI, 405.2-803.4) in 2019, with an AAPC of -0.293 (95% CI, -0.323-[-]0.263). Although the prevalence rates of cataracts, age-related macular degeneration, glaucoma, and near vision loss showed increasing trends from 1990 to 2019, the DALY rates indicated a downward trend for all blindness-causing diseases. The burden is heavier for women and in low Socio-demographic Index (SDI) regions.<br><br>CONCLUSIONS: Despite a decline from 2001 to 2019, the burden of blindness and vision loss, measured by prevalence and DALYs, continues to rise after adjusting for population growth and aging. Blindness and vision loss are significant public health burdens, especially for women and in low-SDI regions.},
}
@article {pmid38454846,
year = {2024},
author = {Neelamegam, V and Surya, RJ and Venkatakrishnan, P and Sharma, T and Raman, R},
title = {Association of eGFR with stages of diabetic retinopathy and age-related macular degeneration in Indian population.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {7},
pages = {968-975},
pmid = {38454846},
issn = {1998-3689},
mesh = {Humans ; Male ; Female ; India/epidemiology ; Cross-Sectional Studies ; *Glomerular Filtration Rate ; *Diabetic Retinopathy/epidemiology/diagnosis/physiopathology ; Middle Aged ; Aged ; *Macular Degeneration/epidemiology/diagnosis/physiopathology ; Risk Factors ; Rural Population/statistics &amp; numerical data ; Incidence ; Urban Population ; Prevalence ; Population Surveillance/methods ; Retrospective Studies ; Adult ; Disease Progression ; },
abstract = {PURPOSE: To investigate the influence of glomerular filtration rate in renal disease decline and its association with diabetic retinopathy (DR) and age-related macular degeneration (ARMD) in patients in South India.<br><br>METHODS: A population-based cross-sectional study was conducted including participants with DR and ARMD recruited from urban and rural populations. The data collection included medical history, anthropometric measurements, and ophthalmic work-up. The estimated glomerular filtration rate (eGFR) was calculated using the equation of chronic kidney disease-epidemiology collaboration (CKD-EPI). The grading of AMD was done by a single experienced (more than 5 years) vitreoretinal surgeon as per the International ARM Epidemiological Study Group and it was staged based on grading in the worsened eye.<br><br>RESULTS: A decline in eGFR was observed as the severity of DR increased (P < 0.001). Baseline characteristics such as age (P < 0.001), duration of diabetes (P < 0.001), gender (P < 0.001), creatinine (P < 0.001), albumin to creatinine ratio (ACR; P < 0.001), albuminuria (P = 0.023), blood urea (P < 0.001), and high-density lipoprotein (HDL; P = 0.003) were found to be statistically significant. The risk for developing DR with CKD was found to be 5 times higher in male patients compared to female patients. Age and high blood urea level, diastolic blood pressure, mild and moderate DR were the risk factors associated with CKD. A decline in eGFR was observed as the severity of ARMD increased (P < 0.001). The risk factors associated with CKD were age, gender, smoking, alcohol consumed, presence of hypertension, duration of diabetes, systolic and diastolic blood pressure, history of diabetes, body mass index (BMI), serum triglycerides, and serum HDL cholesterol.<br><br>CONCLUSION: Reduced eGFR values were associated with an increase in the severity of DR and ARMD.},
}
@article {pmid38453199,
year = {2024},
author = {Reeves, BC and Wickens, R and O'Connor, SR and Gidman, EA and Ward, E and Treanor, C and Peto, T and Burton, BJL and Knox, PC and Lotery, A and Sivaprasad, S and Donnelly, M and Rogers, CA and Hogg, RE},
title = {Descriptive study of the challenges when implementing an app for patients with neovascular age-related macular degeneration to monitor their vision at home.},
journal = {BMJ open},
volume = {14},
number = {3},
pages = {e077196},
pmid = {38453199},
issn = {2044-6055},
mesh = {Humans ; *Mobile Applications ; Smartphone ; *Telemedicine ; *Macular Degeneration/therapy ; },
abstract = {OBJECTIVES: Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack).<br><br>DESIGN: Diagnostic Test Accuracy study.<br><br>SETTING: Six UK hospitals.<br><br>METHODS: The study provides an example of the real-world implementation of such apps across health sectors in an older population. Challenges described include the following: (1) frequency and reason for incoming calls made to a helpline and outgoing calls made to participants; (2) frequency and duration of events responsible for the tests being unavailable; and (3) other technical and logistical challenges.<br><br>RESULTS: Patients (n=297) in the study were familiar with technology; 252/296 (85%) had internet at home and 197/296 (67%) had used a smartphone. Nevertheless, 141 (46%) called the study helpline, more often than anticipated. Of 435 reasons for calling, all but 42 (10%) related to testing with the apps or hardware, which contributed to reduced adherence. The team made at least one call to 133 patients (44%) to investigate why data had not been transmitted. Multibit and MyVisionTrack apps were unavailable for 15 and 30 of 1318 testing days for reasons which were the responsibility of the app providers. Researchers also experienced technical challenges with a multiple device management system. Logistical challenges included regulations for transporting lithium-ion batteries and malfunctioning chargers.<br><br>CONCLUSIONS: Implementation of similar technologies should incorporate a well-resourced helpline and build in additional training time for participants and troubleshooting time for staff. There should also be robust evidence that chosen technologies are fit for the intended purpose.<br><br>TRIAL REGISTRATION NUMBER: ISRCTN79058224.},
}
@article {pmid38452795,
year = {2024},
author = {Kalloniatis, M and Wang, H and Phu, J and Tong, J and Armitage, J},
title = {Optical coherence tomography angiography in the diagnosis of ocular disease.},
journal = {Clinical &amp; experimental optometry},
volume = {107},
number = {5},
pages = {482-498},
doi = {10.1080/08164622.2024.2323603},
pmid = {38452795},
issn = {1444-0938},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Eye Diseases/diagnostic imaging/diagnosis ; Retinal Vessels/diagnostic imaging ; Fundus Oculi ; },
abstract = {Clinical imaging provided by optical coherence tomography (OCT) and its variant, OCT-angiography (OCT-A), has revolutionised eyecare practice. The imaging techniques allow for the identification and quantification of ocular structures, supporting the diagnosis and prognosis of eye disease. In this review, an overview of the usefulness of OCT-A imaging in the diagnosis and management of a range of ocular conditions is provided when used in isolation or in combination with other imaging modalities and measures of visual function (visual field results). OCT-A imaging has the capacity to identify and quantify ocular vasculature non-invasively, thereby assisting the clinician in the diagnosis or to determine the efficacy of intervention in ocular conditions impacting retinal vasculature. Thus, additional clinically useful information can be obtained in eye diseases involving conditions such as those impacting retinal vessel occlusion, in diabetic retinopathy, inherited retinal dystrophy, age-related macular degeneration, choroidal neovascularisation and optic nerve disorders. Through a clinical case series, various ocular conditions are reviewed, and the impact of OCT-A imaging is discussed. Although OCT-A imaging has great promise and is already used in clinical management, there is a lack of set standards to characterise altered vascular features in disease and consequently for prognostication, primarily due to a lack of large-scale clinical trials and variability in OCT-A algorithms when generating quantitative parameters.},
}
@article {pmid38452352,
year = {2024},
author = {Wu, Z and Hodgson, LAB and Goh, KL and Guymer, RH},
title = {COMPLETE RETINAL PIGMENT EPITHELIAL AND OUTER RETINAL ATROPHY IN AGE-RELATED MACULAR DEGENERATION: A Longitudinal Evaluation.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {7},
pages = {1224-1231},
doi = {10.1097/IAE.0000000000004080},
pmid = {38452352},
issn = {1539-2864},
support = {APP1027624//National Health and Medical Research Council/ ; GNT1194667//National Health and Medical Research Council/ ; #2008382//National Health and Medical Research Council/ ; N/A//Macular Disease Foundation Australia/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; *Geographic Atrophy/diagnosis ; *Disease Progression ; *Macular Degeneration/diagnosis ; Follow-Up Studies ; Aged, 80 and over ; Visual Acuity ; Fluorescein Angiography/methods ; Middle Aged ; Prospective Studies ; Atrophy ; Retinal Drusen/diagnosis ; },
abstract = {PURPOSE: There is a need for robust earlier biomarkers of atrophic age-related macular degeneration that could act as surrogate endpoints for geographic atrophy (GA) in early interventional trials. This study sought to examine the risk of progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) to the traditional atrophic endpoint of GA on color fundus photography. This study also compared the risk of progression for cRORA to that associated with the specific optical coherence tomography features that define nascent GA (nGA), a strong predictor of GA development.<br><br>METHODS: One hundred forty participants with bilateral large drusen at baseline underwent optical coherence tomography imaging and color fundus photography at 6-month intervals for up to 36 months. Optical coherence tomography volume scans were graded for the presence of cRORA and nGA, and color fundus photographs were graded for the presence of GA. The association and rate of progression to GA for cRORA and nGA were examined.<br><br>RESULTS: Both cRORA and nGA were significantly associated with GA development (adjusted hazard ratio, 65.7 and 76.8 respectively; both P < 0.001). The probability of progression of cRORA to GA over 24 months (26%) was significantly lower than the probability of progression of nGA (38%; P = 0.039).<br><br>CONCLUSION: This study confirmed that cRORA was a significant risk factor for developing GA, although its rate of progression was slightly lower compared with nGA. While requiring replication in future studies, these findings suggest that the specific features of photoreceptor degeneration used to define nGA appear important when assessing the risk of progression.},
}
@article {pmid38451532,
year = {2024},
author = {Colucciello, M},
title = {Letter to the Editor: Steroid/AntiVascular Endothelial Growth Factor Combination Therapy for Neovascular Age-Related Macular Degeneration.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {40},
number = {3},
pages = {197-198},
doi = {10.1089/jop.2024.0013},
pmid = {38451532},
issn = {1557-7732},
mesh = {Humans ; Endothelial Growth Factors/therapeutic use ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; *Macular Degeneration/drug therapy ; Steroids/therapeutic use ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Retrospective Studies ; },
}
@article {pmid38451452,
year = {2024},
author = {Sacconi, R and Servillo, A and Rissotto, F and Bottazzi, L and Costanzo, E and Polito, MS and Tombolini, B and Parravano, M and Bandello, F and Querques, G},
title = {Macular Neovascularization Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Treatment Response to Anti-VEGF at 2-Year Follow-up.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {5},
pages = {1211-1222},
pmid = {38451452},
issn = {2193-8245},
abstract = {INTRODUCTION: To characterize the response to antivascular endothelial growth factor (VEGF) treatment of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) with subclinical angioid streaks (AS) during a 2-year follow-up.<br><br>METHODS: Retrospective, longitudinal, case-control, and multicentric study. Among a cohort of neovascular AMD population, we selected patients with subclinical AS and treatment-na&#xef;ve MNV treated with anti-VEGF for a 2-year follow-up. An age- and sex-matched control group with treatment-na&#xef;ve MNV secondary to AMD without subclinical AS was selected. Demographics and differences in treatment response (i.e., number of injections needed, anatomical and functional outcomes) between the two groups were analyzed.<br><br>RESULTS: Among 102 eyes of 102 patients with neovascular AMD, 34 eyes of 34 patients (82&#x2009;&#xb1;&#x2009;6&#xa0;years old) were included in the subclinical AS group, whereas 68 eyes of 68 patients (81&#x2009;&#xb1;&#x2009;6&#xa0;years old, p&#x2009;=&#x2009;0.342) in the control group. All eyes with subclinical AS presented RPD compared to 56% of eyes without subclinical AS (p&#x2009;<&#x2009;0.001). During the 2-year follow-up, eyes with subclinical AS needed more injections (10.6&#x2009;&#xb1;&#x2009;3.2 vs 8.3&#x2009;&#xb1;&#x2009;3.1 injections for eyes with and without subclinical AS, respectively, p&#x2009;<&#x2009;0.001). Visual acuity (VA) decreased during the treatment (from 0.53&#x2009;&#xb1;&#x2009;0.37 at the baseline to 0.69&#x2009;&#xb1;&#x2009;0.45 LogMAR at 2-year follow-up, p&#x2009;=&#x2009;0.044) in eyes with subclinical AS; no VA changes were observed in the control group (p&#x2009;=&#x2009;0.798). RPE atrophy at the end of the 2-year follow-up affected 74% of cases with subclinical AS and 29% of cases of the control group (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: MNVs secondary to AMD with subclinical AS are characterized by worse functional and anatomical outcomes after 2-year anti-VEGF treatment compared to MNV secondary to AMD without subclinical AS, supporting the different pathophysiological mechanisms involved in this recently described AMD phenotype.},
}
@article {pmid38450715,
year = {2025},
author = {Alsini, R and Almuhaimeed, A and Ali, F and Khalid, M and Farrash, M and Masmoudi, A},
title = {Deep-VEGF: deep stacked ensemble model for prediction of vascular endothelial growth factor by concatenating gated recurrent unit with two-dimensional convolutional neural network.},
journal = {Journal of biomolecular structure &amp; dynamics},
volume = {43},
number = {16},
pages = {8893-8903},
doi = {10.1080/07391102.2024.2323144},
pmid = {38450715},
issn = {1538-0254},
mesh = {*Vascular Endothelial Growth Factor A/chemistry/genetics ; *Neural Networks, Computer ; *Deep Learning ; Humans ; *Computational Biology/methods ; Algorithms ; Convolutional Neural Networks ; },
abstract = {Vascular endothelial growth factor (VEGF) is involved in the development and progression of various diseases, including cancer, diabetic retinopathy, macular degeneration and arthritis. Understanding the role of VEGF in various disorders has led to the development of effective treatments, including anti-VEGF drugs, which have significantly improved therapeutic methods. Accurate VEGF identification is critical, yet experimental identification is expensive and time-consuming. This study presents Deep-VEGF, a novel computational model for VEGF prediction based on deep-stacked ensemble learning. We formulated two datasets using primary sequences. A novel feature descriptor named K-Space Tri Slicing-Bigram position-specific scoring metrix (KSTS-BPSSM) is constructed to extract numerical features from primary sequences. The model training is performed by deep learning techniques, including gated recurrent unit (GRU), generative adversarial network (GAN) and convolutional neural network (CNN). The GRU and CNN are ensembled using stacking learning approach. KSTS-BPSSM-based ensemble model secured the most accurate predictive outcomes, surpassing other competitive predictors across both training and testing datasets. This demonstrates the potential of leveraging deep learning for accurate VEGF prediction as a powerful tool to accelerate research, streamline drug discovery and uncover novel therapeutic targets. This insightful approach holds promise for expanding our knowledge of VEGF's role in health and disease.},
}
@article {pmid38450631,
year = {2024},
author = {Nam, KT and Yun, C and Lee, YJ and Choi, M and Kang, D and Oh, J},
title = {Visual Outcome and Fluid Changes Between Eyes With Polypoidal Choroidal Vasculopathy Receiving Biosimilar CKD-701 or Reference Ranibizumab Therapy: A Post Hoc Analysis of a Phase 3 Randomized Clinical Trial.},
journal = {Current eye research},
volume = {49},
number = {6},
pages = {663-670},
doi = {10.1080/02713683.2024.2323506},
pmid = {38450631},
issn = {1460-2202},
mesh = {Humans ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Visual Acuity/physiology ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Intravitreal Injections ; *Tomography, Optical Coherence ; Aged ; *Fluorescein Angiography ; *Biosimilar Pharmaceuticals/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Polyps/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Choroid/blood supply/pathology ; Middle Aged ; Subretinal Fluid ; Follow-Up Studies ; Fundus Oculi ; Double-Blind Method ; Polypoidal Choroidal Vasculopathy ; },
abstract = {PURPOSE: To compare the visual outcome and fluid features of a proposed biosimilar, CKD-701, versus the reference ranibizumab in eyes with polypoidal choroidal vasculopathy (PCV).<br><br>METHODS: This was a post hoc analysis of a phase 3 randomized clinical trial assessing the efficacy and safety of CKD-701 and ranibizumab. A total of 73 PCV eyes were assigned randomly to either CKD-701 (36 eyes) or ranibizumab (37 eyes). The mean changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) volume, and fluid features were compared.<br><br>RESULTS: After three loading injections, the mean change in BCVA (letters) was +7.50 in the CKD-701 group and +6.32 in the ranibizumab group (p&#x2009;=&#x2009;.447). The changes in CRT and PED volume of the CKD-701 group (-107.25&#x2009;&#xb1;&#x2009;102.66&#x2009;&#x3bc;m and -0.22&#x2009;&#xb1;&#x2009;0.46&#x2009;mm[3]) were similar to those of the ranibizumab group (-96.78&#x2009;&#xb1;&#x2009;105.00&#x2009;&#x3bc;m and -0.23&#x2009;&#xb1;&#x2009;0.54&#x2009;mm[3]) (p&#x2009;=&#x2009;.668 and p&#x2009;=&#x2009;.943, respectively). Proportions of eyes with subretinal, intraretinal and sub-retinal pigment epithelium (RPE) fluids after three loading injections were not different between CKD-701 group (33.3%, 13.9% and 42.9%) and ranibizumab group (51.4%, 16.2% and 40.0%) (p&#x2009;=&#x2009;.071, p&#x2009;=&#x2009;1.000 and p&#x2009;=&#x2009;.808). The visual and anatomical changes were similar between two groups at month 6 and 12 (all, p&#x2009;>&#x2009;.05).<br><br>CONCLUSION: Biosimilar CKD-701 monotherapy resulted in comparable visual and anatomical changes to those achieved with reference ranibizumab in PCV eyes.},
}
@article {pmid38450381,
year = {2024},
author = {Contemori, G and Maniglia, M and Guénot, J and Soler, V and Cherubini, M and Cottereau, BR and Trotter, Y},
title = {tRNS boosts visual perceptual learning in participants with bilateral macular degeneration.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1326435},
pmid = {38450381},
issn = {1663-4365},
abstract = {Perceptual learning (PL) has shown promise in enhancing residual visual functions in patients with age-related macular degeneration (MD), however it requires prolonged training and evidence of generalization to untrained visual functions is limited. Recent studies suggest that combining transcranial random noise stimulation (tRNS) with perceptual learning produces faster and larger visual improvements in participants with normal vision. Thus, this approach might hold the key to improve PL effects in MD. To test this, we trained two groups of MD participants on a contrast detection task with (n = 5) or without (n = 7) concomitant occipital tRNS. The training consisted of a lateral masking paradigm in which the participant had to detect a central low contrast Gabor target. Transfer tasks, including contrast sensitivity, near and far visual acuity, and visual crowding, were measured at pre-, mid and post-tests. Combining tRNS and perceptual learning led to greater improvements in the trained task, evidenced by a larger increment in contrast sensitivity and reduced inhibition at the shortest target to flankers' distance. The overall amount of transfer was similar between the two groups. These results suggest that coupling tRNS and perceptual learning has promising potential applications as a clinical rehabilitation strategy to improve vision in MD patients.},
}
@article {pmid38450199,
year = {2024},
author = {Esteve-Garcia, A and Cobos, E and Sau, C and Padró-Miquel, A and Català-Mora, J and Barberán-Martínez, P and Millán, JM and García-García, G and Aguilera, C},
title = {Deciphering complexity: TULP1 variants linked to an atypical retinal dystrophy phenotype.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1352063},
pmid = {38450199},
issn = {1664-8021},
abstract = {Introduction: TULP1 exemplifies the remarkable clinical and genetic heterogeneity observed in inherited retinal dystrophies. Our research describes the clinical and molecular characteristics of a patient manifesting an atypical retinal dystrophy pattern, marked by the identification of both a previously unreported and a rarely encountered TULP1 variant. Methods: Whole-exome sequencing was performed to identify potential causative variants. The pathogenicity of the identified TULP1 variants was evaluated through in silico predictors and a minigene splice assay, specifically designed to assess the effect of the unreported TULP1 variant. Results: We identified two TULP1 gene variants in a patient exhibiting unusual and symmetrical alterations in both retinas, characterized by an increase in autofluorescence along the distribution of retinal vessels. These variants included a known rare missense variant, c.1376T>C, and a novel splice site variant, c.822G>T. For the latter variant (c.822G>T), we conducted a minigene splice assay that demonstrated the incorporation of a premature stop codon. This finding suggests a likely activation of the nonsense-mediated mRNA decay mechanism, ultimately resulting in the absence of protein production from this allele. Segregation analysis confirmed that these variants were in trans. Discussion: Our data support that individuals with biallelic TULP1 variants may present with a unique pattern of macular degeneration and periarteriolar vascular pigmentation. This study highlights the importance of further clinical and molecular characterization of TULP1 variants to elucidate genotype-phenotype correlations in the context of inherited retinal dystrophies.},
}
@article {pmid38449553,
year = {2023},
author = {Adenuga, OO and Udoh, ME and Okonkwo, ON and Ovienria, W and Nkanga, DG and Oyekunle, I and Ibanga, AA and Akanbi, T and Agweye, CT and , },
title = {Exudative Retinal Detachment in Nigerians: Demographics and Causes.},
journal = {Journal of the West African College of Surgeons},
volume = {13},
number = {4},
pages = {63-66},
pmid = {38449553},
issn = {2992-5827},
abstract = {BACKGROUND: Exudative retinal detachment (ERD) is a rare type of retinal detachment (RD), and information on its causes and presentation in Nigerians and Black Africans is scarce.<br><br>AIM: To report the prevalence, vision at presentation, and causes of ERD in a cohort of RD patients.<br><br>MATERIALS AND METHODS: A prospective, multicentre, hospital-based study. We examined consecutive eyes diagnosed with ERD in ophthalmic patients seen within 1 year in four ophthalmic hospitals in Nigeria. The patients had a complete eye examination, including visual acuity, intraocular pressure measurement, slit lamp examination of the anterior segment, dilated fundus examination, and other ancillary investigations. Statistical analysis was done using SPSS version 22.0.<br><br>RESULTS: Nine out of 237 patients were diagnosed with ERD, giving a hospital-based prevalence of 3.8% of RDs. The mean age of patients was 45.8&#x2009;&#xb1;&#x2009;21.6 years (6 months-80 years), male:female = 2:1. ERD was bilateral in one patient and unilateral in eight patients. There was no gender association (P = 0.84), but systemic disease was associated with a risk of ERD (P = 0.001). Five out of 9 (55.6%) patients had an associated systemic disease. The systemic diseases include two patients (40%) who had chronic renal failure, two patients (40%) who had systemic hypertension, and one patient (10%) who had lung cancer. Other ocular causes of ERD include post endophthalmitis, coats disease, and age-related macular degeneration in one eye each. 80 % of eyes were blind at presentation.<br><br>CONCLUSION: ERD is a rare form of RD in Nigerians and is associated with systemic diseases. There are inflammatory, neoplastic, vascular, and degenerative causes of ERD. At presentation, most eyes are blind. Early presentation will be beneficial in salvaging vision. Also, awareness of the occurrence and causes of ERD should be created amongst eye care practitioners.},
}
@article {pmid38449080,
year = {2024},
author = {Chadoulos, N and Dastiridou, A and Mitsios, A and Tsinopoulos, I and Kalogeropoulos, C and Androudi, S},
title = {Laser flare photometry in eyes receiving brolucizumab intravitreal injections for age related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {34},
number = {6},
pages = {2007-2013},
doi = {10.1177/11206721241236917},
pmid = {38449080},
issn = {1724-6016},
mesh = {Humans ; *Intravitreal Injections ; Aged ; Prospective Studies ; Male ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Photometry ; *Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; *Aqueous Humor/metabolism ; Aged, 80 and over ; *Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography ; Lasers ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To measure aqueous flare levels in treatment naïve eyes suffering from wet age- related macular degeneration (wAMD) treated with intravitreal brolucizumab.<br><br>METHODS: Patients with treatment na&#xef;ve wAMD in one eye were prospectively enrolled. Flare levels were measured with laser flare photometry at baseline, 1 day and 1 month after each of the 3 monthly injections during the loading phase.<br><br>RESULTS: Twenty-two eyes from 22 patients aged 76.7&#x2009;&#xb1;&#x2009;6.0 years were enrolled. Flare values were 10.6&#x2009;&#xb1;&#x2009;3.7 photons/msec at baseline and 12.6&#x2009;&#xb1;&#x2009;5.8 photons/msec at the last follow up visit, 1 month after the third injection (p&#x2009;=&#x2009;0.289, repeated measures ANOVA). The mean change in flare after the first injection was 4.2&#x2009;&#xb1;&#x2009;3.6. photons/msec, 6.6&#x2009;&#xb1;&#x2009;8.9 photons/msec after the 2nd and 8.6&#x2009;&#xb1;&#x2009;20.8 photons/msec after the 3rd injection (p&#x2009;=&#x2009;0.640, repeated measures ANOVA). No patient had clinical signs of intraocular inflammation.<br><br>CONCLUSIONS: Eyes receiving brolucizumab injections for wAMD showed similar flare at baseline, during and 1 month after completion of three-monthly intravitreal injections. There was no evidence of subclinical inflammation during the loading phase of brolucizumab based on laser flare photometry measurements.},
}
@article {pmid38448961,
year = {2024},
author = {Tey, KY and Cheong, EZK and Ang, M},
title = {Potential applications of artificial intelligence in image analysis in cornea diseases: a review.},
journal = {Eye and vision (London, England)},
volume = {11},
number = {1},
pages = {10},
pmid = {38448961},
issn = {2326-0254},
abstract = {Artificial intelligence (AI) is an emerging field which could make an intelligent healthcare model a reality and has been garnering traction in the field of medicine, with promising results. There have been recent developments in machine learning and/or deep learning algorithms for applications in ophthalmology-primarily for diabetic retinopathy, and age-related macular degeneration. However, AI research in the field of cornea diseases is relatively new. Algorithms have been described to assist clinicians in diagnosis or detection of cornea conditions such as keratoconus, infectious keratitis and dry eye disease. AI may also be used for segmentation and analysis of cornea imaging or tomography as an adjunctive tool. Despite the potential advantages that these new technologies offer, there are challenges that need to be addressed before they can be integrated into clinical practice. In this review, we aim to summarize current literature and provide an update regarding recent advances in AI technologies pertaining to corneal diseases, and its potential future application, in particular pertaining to image analysis.},
}
@article {pmid38448469,
year = {2024},
author = {Schlosser, T and Beuth, F and Meyer, T and Kumar, AS and Stolze, G and Furashova, O and Engelmann, K and Kowerko, D},
title = {Visual acuity prediction on real-life patient data using a machine learning based multistage system.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {5532},
pmid = {38448469},
issn = {2045-2322},
support = {01ZZ2101E//Federal Ministry of Education and Research/ ; 01ZZ2101C//Federal Ministry of Education and Research/ ; },
mesh = {Humans ; Female ; Male ; *Diabetic Retinopathy/diagnostic imaging ; *Macular Edema/diagnosis/drug therapy ; Visual Acuity ; Documentation ; Machine Learning ; *Macular Degeneration/diagnosis ; },
abstract = {In ophthalmology, intravitreal operative medication therapy (IVOM) is a widespread treatment for diseases related to the age-related macular degeneration (AMD), the diabetic macular edema, as well as the retinal vein occlusion. However, in real-world settings, patients often suffer from loss of vision on time scales of years despite therapy, whereas the prediction of the visual acuity (VA) and the earliest possible detection of deterioration under real-life conditions is challenging due to heterogeneous and incomplete data. In this contribution, we present a workflow for the development of a research-compatible data corpus fusing different IT systems of the department of ophthalmology of a German maximum care hospital. The extensive data corpus allows predictive statements of the expected progression of a patient and his or her VA in each of the three diseases. For the disease AMD, we found out a significant deterioration of the visual acuity over time. Within our proposed multistage system, we subsequently classify the VA progression into the three groups of therapy "winners", "stabilizers", and "losers" (WSL classification scheme). Our OCT biomarker classification using an ensemble of deep neural networks results in a classification accuracy (F1-score) of over 98%, enabling us to complete incomplete OCT documentations while allowing us to exploit them for a more precise VA modelling process. Our VA prediction requires at least four VA examinations and optionally OCT biomarkers from the same time period to predict the VA progression within a forecasted time frame, whereas our prediction is currently restricted to IVOM/no therapy. We achieve a final prediction accuracy of 69% in macro average F1-score, while being in the same range as the ophthalmologists with 57.8 and 50 ± 10.7 % F1-score.},
}
@article {pmid38447458,
year = {2024},
author = {Somers, FM and Malek, G},
title = {Estrogen related receptor alpha: Potential modulator of age-related macular degeneration.},
journal = {Current opinion in pharmacology},
volume = {75},
number = {},
pages = {102439},
pmid = {38447458},
issn = {1471-4973},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY032751/EY/NEI NIH HHS/United States ; R01 EY035126/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *ERRalpha Estrogen-Related Receptor ; *Macular Degeneration/drug therapy/metabolism/pathology ; Aging/physiology ; Receptors, Cytoplasmic and Nuclear ; Eye/metabolism ; },
abstract = {To develop effective therapies for complex blinding diseases such as age-related macular degeneration (AMD), identification of mechanisms involved in its initiation and progression is needed. The estrogen-related receptor alpha (ESRRA) is an orphan nuclear receptor that regulates several AMD-associated pathogenic pathways. However, it has not been investigated in detail in the ocular posterior pole during aging or in AMD. This review delves into the literature highlighting the significance of ESRRA as a molecular target that may be important in the pathobiology of AMD, and discusses data available supporting the targeting of this receptor signaling pathway as a therapeutic option for AMD.},
}
@article {pmid38446902,
year = {2024},
author = {Yang, Q and Cai, Y and Ma, Q and Xiong, A and Xu, P and Zhang, Z and Xu, J and Zhou, Y and Liu, Z and Zhao, D and Asara, J and Li, W and Shi, H and Caldwell, RB and Sodhi, A and Huo, Y},
title = {Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice.},
journal = {Science translational medicine},
volume = {16},
number = {737},
pages = {eadk3868},
pmid = {38446902},
issn = {1946-6242},
support = {R01 EY030500/EY/NEI NIH HHS/United States ; R01 EY033369/EY/NEI NIH HHS/United States ; R01 EY033737/EY/NEI NIH HHS/United States ; K99 EY034577/EY/NEI NIH HHS/United States ; P30 EY031631/EY/NEI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Animals ; Mice ; Aged ; Endothelial Cells ; *Cardiovascular Diseases ; *Choroidal Neovascularization/drug therapy ; Disease Models, Animal ; Endothelial-Mesenchymal Transition ; },
abstract = {Anti-vascular endothelial growth factor therapy has had a substantial impact on the treatment of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults. Despite treatment, many patients with nAMD still develop severe and irreversible visual impairment because of the development of subretinal fibrosis. We recently reported the anti-inflammatory and antiangiogenic effects of inhibiting the gene encoding adenosine receptor 2A (Adora2a), which has been implicated in cardiovascular disease. Here, using two mouse models of subretinal fibrosis (mice with laser injury-induced CNV or mice with a deficiency in the very low-density lipoprotein receptor), we found that deletion of Adora2a either globally or specifically in endothelial cells reduced subretinal fibrosis independently of angiogenesis. We showed that Adora2a-dependent endothelial-to-mesenchymal transition contributed to the development of subretinal fibrosis in mice with laser injury-induced CNV. Deficiency of Adora2a in cultured mouse and human choroidal endothelial cells suppressed induction of the endothelial-to-mesenchymal transition. A metabolomics analysis of cultured human choroidal endothelial cells showed that ADORA2A knockdown with an siRNA reversed the increase in succinate because of decreased succinate dehydrogenase B expression under fibrotic conditions. Pharmacological inhibition of ADORA2A with a small-molecule KW6002 in both mouse models recapitulated the reduction in subretinal fibrosis observed in mice with genetic deletion of Adora2a. ADORA2A inhibition may be a therapeutic approach to treat subretinal fibrosis associated with nAMD.},
}
@article {pmid38446282,
year = {2024},
author = {Arrigo, A and Saladino, A and Aragona, E and Barresi, C and Mularoni, C and Bandello, F and Battaglia Parodi, M},
title = {Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {5},
pages = {1185-1196},
pmid = {38446282},
issn = {2193-8245},
abstract = {INTRODUCTION: Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting.<br><br>METHODS: This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24&#xa0;months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points.<br><br>RESULTS: We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79&#x2009;&#xb1;&#x2009;8&#xa0;years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p&#x2009;>&#x2009;0.05).<br><br>CONCLUSIONS: We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.},
}
@article {pmid38446199,
year = {2024},
author = {Creer, R and Boonarpha, N and Gould, G and Rajai, A and Chhabra, R},
title = {Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {8},
pages = {2411-2419},
pmid = {38446199},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Visual Acuity ; *Intravitreal Injections ; *Radiosurgery/methods ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged ; *Tomography, Optical Coherence ; Follow-Up Studies ; *Wet Macular Degeneration/diagnosis/drug therapy/therapy ; Treatment Outcome ; *Ranibizumab/administration &amp; dosage ; Middle Aged ; Fluorescein Angiography ; Combined Modality Therapy ; Bevacizumab/administration &amp; dosage ; Aged, 80 and over ; Fundus Oculi ; Macula Lutea/pathology ; },
abstract = {INTRODUCTION: Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time.<br><br>OBJECTIVE: To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI).<br><br>METHOD: A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36&#xa0;months after patients received SRT and compared to the same time interval prior to SRT.<br><br>RESULTS: Follow-up data at 12, 24, and 36&#xa0;months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p&#x2009;<&#x2009;0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p&#x2009;<&#x2009;0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36&#xa0;months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.},
}
@article {pmid38444247,
year = {2024},
author = {Franceschelli, S and D'Andrea, P and Farina, M and Gallenga, CE and Grilli, A and Pesce, M and Di Donato, A and Lucchetta, D and Ambrosini, G and Benedetti, S and Benedetti, M and Lobefalo, L},
title = {Short term effects of extremely low irradiance photobiomodulation on retinal function, in age related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {34},
number = {6},
pages = {2014-2019},
doi = {10.1177/11206721241236919},
pmid = {38444247},
issn = {1724-6016},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; *Tomography, Optical Coherence ; Prospective Studies ; Aged ; *Retina/physiopathology/radiation effects ; Low-Level Light Therapy/methods ; Macular Degeneration/physiopathology/radiotherapy ; Aged, 80 and over ; Visual Field Tests ; Visual Fields/physiology ; Treatment Outcome ; },
abstract = {BACKGROUND: recently much studies evidenced the potential role of photo-biomodulation (PBM) in patients affected by Age-related Macular Degeneration (AMD). We designed a new wearable device for self-medication that employs the same broadband red light described in literature, but with extremely low irradiance.<br><br>AIM: to demonstrate the safety and effectiveness of low-fluence light stimulations emitted by a LED source with appropriate wavelengths through our new device in improving short-term visual function in patients affected by severe non neovascular AMD.<br><br>MATERIALS AND METHODS: we prospectively enrolled patients affected by severe non-neovascular AMD with a relative sparing of the foveal region. All the patients were randomly assigned in placebo or in treatment group. The treatment consisted of 10 sessions of 10-min each, using the new device comprised of micro-LEDs that emitted light onto an amorphous support assembled within Metallic eyeglasses. The placebo group blindly underwent the same number of PBM sessions with the micro-LED turned off. Before and after each placebo/treatment sessions all the patients received: optical coherence tomography (OCT), Best-Corrected Visual Acuity (BCVA) and Microperimetry (MP).<br><br>RESULTS: no significant differences in the anatomical parameters were observed in the two groups. The MP mean sensitivity and the central visual function both far and near significantly improved in the treated group (respectively p&#x2009;<&#x2009;0.001, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: our pivotal demonstrated that the LED PBM delivered through our new device is a safe and effective tool for improving short-term visual function in patients affected by severe non-neovascular AMD.},
}
@article {pmid38443987,
year = {2024},
author = {Brandli, A and Vessey, KA and Fletcher, EL},
title = {The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome.},
journal = {Journal of neuroinflammation},
volume = {21},
number = {1},
pages = {64},
pmid = {38443987},
issn = {1742-2094},
mesh = {Animals ; *Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Toll-Like Receptors ; Inflammation ; *Macular Degeneration ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, characterised by the dysfunction and death of the photoreceptors and retinal pigment epithelium (RPE). Innate immune cell activation and accompanying para-inflammation have been suggested to contribute to the pathogenesis of AMD, although the exact mechanism(s) and signalling pathways remain elusive. Pattern recognition receptors (PRRs) are essential activators of the innate immune system and drivers of para-inflammation. Of these PRRs, the two most prominent are (1) Toll-like receptors (TLR) and (2) NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3)-inflammasome have been found to modulate the progression of AMD. Mutations in TLR2 have been found to be associated with an increased risk of developing AMD. In animal models of AMD, inhibition of TLR and NLRP3 has been shown to reduce RPE cell death, inflammation and angiogenesis signalling, offering potential novel treatments for advanced AMD. Here, we examine the evidence for PRRs, TLRs2/3/4, and NLRP3-inflammasome pathways in macular degeneration pathogenesis.},
}
@article {pmid38443542,
year = {2024},
author = {Ling, JYM and Mansournia, MA and Etminan, M},
title = {Disease latency bias and the protective effect of metformin against age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {9},
pages = {1616-1617},
pmid = {38443542},
issn = {1476-5454},
mesh = {Humans ; *Metformin/therapeutic use ; *Macular Degeneration/prevention &amp; control/drug therapy ; Hypoglycemic Agents/therapeutic use ; },
}
@article {pmid38442827,
year = {2024},
author = {Thomsen, AK and Gøttsche, LF and Hinnerskov, JMV and Falk, MK and Sørensen, TL},
title = {Microperimetry and Structural Risk Factors on OCT in Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {8},
pages = {786-793},
doi = {10.1016/j.oret.2024.02.016},
pmid = {38442827},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Disease Progression ; Fluorescein Angiography/methods ; Follow-Up Studies ; Macula Lutea/pathology/diagnostic imaging ; *Macular Degeneration/physiopathology/diagnosis/complications ; Prospective Studies ; Retina/physiopathology/diagnostic imaging ; Retinal Drusen/diagnosis/physiopathology/etiology ; Risk Factors ; Tomography, Optical Coherence/methods ; Visual Acuity ; Visual Field Tests/methods ; *Visual Fields/physiology ; },
abstract = {PURPOSE: To determine the relationship between structural biomarkers on OCT that increase the risk of disease progression and microperimetric retinal sensitivity in patients with intermediate age-related macular degeneration (iAMD).<br><br>DESIGN: Prospective cross-sectional, observational study.<br><br>PARTICIPANTS: Forty-five eyes of 23 patients with iAMD.<br><br>METHODS: Patients underwent OCT and microperimetry. OCT scans were evaluated for the risk factors intraretinal hyperreflective foci (HRF), hyporeflectivity within drusenoid lesions (HRDL), subretinal drusenoid deposits, double-layer sign (DLS), and drusen volume. Microperimetric retinal sensitivity was analyzed with a 33-point grid covering the macula. With a novel method of determining what part of the retina corresponded to each microperimetry point, a Voronoi diagram was constructed, dividing the macula in cells consisting of the region nearer to each point than any other. The Voronoi diagram was superimposed on the OCT, making it possible to determine the point-to-point location of the OCT risk factors. Univariable and multivariable linear mixed-effect models were used for analysis.<br><br>MAIN OUTCOME MEASURES: Association between microperimetric retinal sensitivity and OCT risk factors at individual measuring points.<br><br>RESULTS: One thousand four hundred seventy-nine points of retinal sensitivity and corresponding structural area on OCT were included in this study. Retinal sensitivity was significantly decreased with presence of the OCT risk factors HRF, HRDL, DLS, and drusen volume (all P < 0.001) when analyzed with the univariable linear mixed-effect model. The multivariable model showed a significant decrease of retinal sensitivity with presence of HRF (P < 0.001), DLS (P&#xa0;= 0.025), and greater drusen volume (P < 0.001).<br><br>CONCLUSIONS: Presence of HRF, DLS, and greater drusen volume, all of which increase the risk of disease progression, is significantly and independently associated with decreased microperimetric retinal sensitivity in patients with iAMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38441066,
year = {2024},
author = {Berkowitz, ST and Finn, AP},
title = {Gene therapy for age-related macular degeneration: potential, feasibility, and pitfalls.},
journal = {Current opinion in ophthalmology},
volume = {35},
number = {3},
pages = {170-177},
pmid = {38441066},
issn = {1531-7021},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; *Biosimilar Pharmaceuticals ; Feasibility Studies ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Genetic Therapy ; },
abstract = {PURPOSE OF REVIEW: The landscape for age-related macular degeneration (AMD) is rapidly changing with addition of biosimilars and now United States Food and Drug Administration (FDA) approved nonneovascular AMD (nnAMD) treatment options. These developments have inspired a burgeoning pipeline of gene therapy approaches focused on similar antivascular endothelial growth factors (VEGF) and complement related pathways. Historic and more recent setbacks in the gene therapy pipeline, including intraocular inflammatory reactions, have raised important concerns for adverse events related to AMD therapeutics both for gene and nongene approaches. The specific clinical profile of these therapeutics approaching later stage clinical trials are complex and under active investigation; however, these options hold promise to disrupt the current landscape and change management paradigms for one of the leading causes of vision loss worldwide.<br><br>RECENT FINDINGS: This review covers current gene therapy approaches for neovascular AMD (nAMD) and nnAMD. Intravitreal, suprachoroidal, and subretinal delivery routes are discussed with attention to technical procedure, capabilities for transgene delivery to target tissue, immunogenicity, and collateral effects. Suprachoroidal delivery is an emerging approach which may bridge some of the practical drawbacks for intravitreal and subretinal methods, though with less elaborated immunologic profile. In parallel to delivery modification, viral vectors have been cultivated to target specific cells, with promising enhancements in adeno-associated viral (AAV) vectors and persistent interest in alternate viral and nonviral delivery vectors. Ongoing questions such as steroid or immunosuppressive regimen and economic considerations from a payer and societal perspective are discussed.<br><br>SUMMARY: The present review discusses emerging gene therapy options which could foster new, more durable nAMD and nnAMD therapeutics. These options will need refinement with regards to route, vector, and dosage, and specialists must decipher the specific clinical risk benefit profile for individual patients. Ongoing concerns for immunogenicity or dosage related adverse events could stifle progress, while further vector development and refined delivery techniques have the potential to change the safety and efficacy of currently options in the pipeline.},
}
@article {pmid38440034,
year = {2024},
author = {Lath, YV and Thool, AR and Jadhav, I},
title = {Regeneration of the Retina Using Pluripotent Stem Cells: A Comprehensive Review.},
journal = {Cureus},
volume = {16},
number = {2},
pages = {e53479},
pmid = {38440034},
issn = {2168-8184},
abstract = {Retinitis pigmentosa and age-related macular degeneration are the most frequent causes of irreversible visual impairment in the world. Existing therapeutic methods could be more effective, underscoring the necessity of new treatments. Reconstructing the retinal photoreceptors through the transplantation of human pluripotent stem cells, representing an attractive approach for restoring vision, has gained momentum. This paper gives an exhaustive account of what has been known in this field, the discoveries made, and the recent progress. This review paper outlines the retina's organisation, cell types, the pathophysiology of retinal injury/degeneration, and the reasoning behind using pluripotent stem cells in retinal regeneration. This article investigates differentiation strategies, molecular components that dictate cell type specification, and the recreation of retinal development in vitro, genetically engineering and manipulating epigenetic marks using various techniques for driving specific cell fates and improving therapy efficacy. Subretinal injection methods, cell encapsulation techniques, scaffold-based approaches, cell sheet transplantation, and their impact on integrating implanted cells into a functional retina are thoroughly reviewed. Using bioengineering approaches, biomaterials and growth factors form a favourable micro-ambience for grafted cells. Issues around safety and efficacy (tumorigenicity, immunological rejection, and long-term integration/functionality) are explored. Moreover, the paper emphasises the significance of rigorous characterisation, immunomodulatory strategies, and clinical and pre-clinical studies to ensure the safety and effectiveness of retinal regeneration therapy. Future perspectives and challenges are presented, looking at fine-tuning differentiation strategies, improving functional integration and regulatory aspects, and using co-therapy and supportive treatments.},
}
@article {pmid38439539,
year = {2024},
author = {Owsley, C and Swain, TA and McGwin, G and Bernard, MM and Clark, ME and Curcio, CA},
title = {Repeatability of Rod-Mediated Dark Adaptation Testing in Normal Aging and Early and Intermediate Age-Related Macular Degeneration.},
journal = {Current eye research},
volume = {49},
number = {7},
pages = {725-730},
pmid = {38439539},
issn = {1460-2202},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Dark Adaptation/physiology ; Aged ; *Retinal Rod Photoreceptor Cells/physiology ; Male ; Female ; Reproducibility of Results ; *Aging/physiology ; *Visual Acuity/physiology ; *Macular Degeneration/physiopathology/diagnosis ; Aged, 80 and over ; Middle Aged ; Vision Tests ; },
abstract = {PURPOSE: The vulnerability of rod photoreceptors in aging and early and intermediate age-related macular degeneration (AMD) has been well documented. Rod-mediated dark adaptation (RMDA) is a measure of the recovery of light sensitivity in rod photoreceptors following a bright light. Delays in RMDA during early and intermediate AMD have been widely reported. For RMDA's promise as an outcome for trials targeted at early and intermediate AMD to be realized, excellent test-retest reliability, its repeatability, must be established.<br><br>METHODS: Test-retest performance in a commonly used RMDA test based on the rod intercept time metric (RIT) was evaluated in participants with early and intermediate AMD and with normal retinal aging with testing approximately 2&#x2009;weeks apart. The test target was placed at 5&#xb0; eccentricity superior to the foveal center, an area with maximal rod loss in aging and AMD. Disease severity was identified by a trained and masked grader of fundus photographs using both the AREDS 9-step and Beckman classification systems. Bland-Altman plots and intra-class correlation coefficients (ICC) evaluated repeatability.<br><br>RESULTS: The analysis sample consisted of 37 older adults (mean age 76&#x2009;years, standard deviation 5), with approximately one-third of the sample in each of three groups - normal aging, early AMD, and intermediate AMD. For the total sample, the ICC was 0.98. For individual AMD groups for both AREDS 9-step and Beckman classifications, the ICCs were also very high ranging from 0.82 to 0.99.<br><br>CONCLUSION: We demonstrated that RMDA testing using the RIT metric has excellent repeatability when target location is at 5&#xb0; in studying older adults from normal aging to intermediate AMD, suggesting the reliable use of this functional measure in trials.},
}
@article {pmid38438351,
year = {2024},
author = {Advani, J and Mehta, PA and Hamel, AR and Mehrotra, S and Kiel, C and Strunz, T and Corso-Díaz, X and Kwicklis, M and van Asten, F and Ratnapriya, R and Chew, EY and Hernandez, DG and Montezuma, SR and Ferrington, DA and Weber, BHF and Segrè, AV and Swaroop, A},
title = {QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {1972},
pmid = {38438351},
issn = {2041-1723},
support = {ZIA EY000450/ImNIH/Intramural NIH HHS/United States ; ZIA EY000546/ImNIH/Intramural NIH HHS/United States ; R01 EY031424/EY/NEI NIH HHS/United States ; P30 EY014104/EY/NEI NIH HHS/United States ; R01 EY028554/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *DNA Methylation/genetics ; Epigenesis, Genetic ; Epigenome ; *Macular Degeneration/genetics ; Retina ; },
abstract = {DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.},
}
@article {pmid38438003,
year = {2024},
author = {Baybora, H},
title = {Perifoveal retinal thickness changes after intravitreal aflibercept injection for choroidal neovascularization in age-related macular degeneration.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {46},
number = {},
pages = {104028},
doi = {10.1016/j.pdpdt.2024.104028},
pmid = {38438003},
issn = {1873-1597},
mesh = {*Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Retrospective Studies ; *Choroidal Neovascularization/drug therapy ; Intravitreal Injections ; *Fovea Centralis/drug effects ; Humans ; Male ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; *Macular Degeneration/drug therapy ; Tomography, Optical Coherence ; Retina/drug effects ; Angiogenesis Inhibitors/administration &amp; dosage ; Visual Acuity/drug effects ; Treatment Outcome ; },
abstract = {OBJECTIVE: There has been some concern that anti-vascular growth factor treatment accelerates the development of macular atrophy in eyes with neovascular age-related macular degeneration. During the treatment with aflibercept, the thickness of choroid may decrease. This may lead to photoreceptor death. The rod cells are more susceptible to atrophic changes than cones during the disease. We aimed to find any thickness changes in the perifoveal outer nuclear layer, where the highest density of rods is found, during the aflibercept intravitreal injection therapy.<br><br>MATERIALS AND METHODS: Retrospectively, forty-two patients who were treated for age-related macular degeneration with choroidal neovascularization were included in the study. After the first three loading doses, intravitreal injections were repeated every two months. Outer nuclear layer thicknesses were measured 2000 &#xb5;m away from the center of the fovea with OCT, at a total of 20 points, located at 180 and 90&#xb0;. The mean of these measurements was obtained before the treatment and 1 year after the therapy. Results were compared by using the Wilcoxon Rank Test.<br><br>RESULTS: The mean visual acuity was 1,11&#xb1;0,287 logMAR at the beginning and increased to 0,53&#xb1;0,32 LogMAR after. Perifoveal thickness was significantly reduced when compared with the thickness before the treatment (p = 0.039, p < 0.05). This result was also significantly lower than the control group thicknesses (p = 0.035, p < 0.05).<br><br>CONCLUSION: Anti-VEGFs can cause loss of phagocytic functions of RPE. The mechanism of the observed thinning of the ONL may be described as follows: VEGF emitted by the RPE normally helps to maintain the choriocapillaris. Thus, injecting an anti-VEGF intravitreally causes RPE atrophy, which leads to a decrease in the choroidal vascular index. This in turn causes first the rods, and later the cones, that are part of the outer nuclear layer, to start to die and disappear, hence the thinning of this layer. As aflibercept consists of parts of the extracellular domain of both the VEGFR1 and VEGFR2 receptors, that are held together by a human IgG1 backbone, this makes the binding of aflibercept to VEGF-A and VEGF-B stronger as compared to the binding of the previously used ranibizumab or bevacizumab (by nearly a factor 100 in the case of the most abundant isoform VEGF-A 165). Besides, aflibercept also binds very well to placental growth factor (PIGF), which is also associated with several ocular diseases.},
}
@article {pmid38435828,
year = {2024},
author = {Huang, C and Wang, Y and Huang, J and Liu, H and Chen, Z and Jiang, Y and Chen, Y and Qian, F},
title = {A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration.},
journal = {Bioengineering &amp; translational medicine},
volume = {9},
number = {2},
pages = {e10632},
pmid = {38435828},
issn = {2380-6761},
abstract = {Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy. However, the intrinsic protein structure can limit the maximum concentration due to stability and solution viscosity. To overcome this challenge, we developed a novel anti-VEGF protein called nanoFc by fusing anti-VEGF nanobodies with a crystallizable fragment (Fc). NanoFc has demonstrated high binding affinity to VEGF165 through multivalency and potent bioactivity in various bioassays. Furthermore, nanoFc maintains satisfactory chemical and physical stability at 4°C over 1 month and is easily injectable at concentrations up to 200 mg/mL due to its unique architecture that yields a smaller shape factor. The design of nanoFc offers a bioengineering strategy to ensure both strong anti-VEGF binding affinity and high protein concentration, with the goal of reducing the frequency of IV injections.},
}
@article {pmid38432561,
year = {2024},
author = {Sesso, HD and Rautiainen, S and Park, SJ and Kim, E and Lee, IM and Glynn, RJ and Buring, JE and Christen, WG},
title = {Intake of Blueberries, Anthocyanins, and Risk of Eye Disease in Women.},
journal = {The Journal of nutrition},
volume = {154},
number = {4},
pages = {1404-1413},
pmid = {38432561},
issn = {1541-6100},
support = {R01 CA047988/CA/NCI NIH HHS/United States ; U01 CA182913/CA/NCI NIH HHS/United States ; UM1 CA182913/CA/NCI NIH HHS/United States ; R01 EY018820/EY/NEI NIH HHS/United States ; R01 HL043851/HL/NHLBI NIH HHS/United States ; R01 HL080467/HL/NHLBI NIH HHS/United States ; RC1 HL099355/HL/NHLBI NIH HHS/United States ; },
mesh = {Middle Aged ; Humans ; Female ; Aged ; Anthocyanins ; *Blueberry Plants ; Follow-Up Studies ; Risk Factors ; *Cataract/epidemiology/prevention &amp; control ; },
abstract = {BACKGROUND: Blueberries and anthocyanins, their key bioactive component, may improve eye health. However, few long-term studies have examined blueberries and anthocyanins with cataract and age-related macular degeneration (AMD).<br><br>OBJECTIVES: To investigate the prospective association between blueberry and anthocyanin intake with incident cataract, total AMD, and visually significant AMD among middle-aged and older women.<br><br>METHODS: A total of 36,653 and 35,402 women initially free of AMD and cataract, respectively, aged &#x2265;45 y from the Women's Health Study provided semiquantitative food frequency questionnaire data on blueberry intake categorized as none, 1-3 servings/mo, 1 serving/wk, or &#x2265;2 servings/wk, plus a combined category of &#x2265;1 serving/wk. Total anthocyanin intake and major subclasses were energy-adjusted and categorized into quintiles. Self-reported risk factors of eye disease were adjusted in multivariable hazard ratios (HRs) (95% confidence intervals [CIs]) of confirmed cataract, AMD, and visually significant AMD with mean follow-up of 11 y.<br><br>RESULTS: Among the participants, 10.5% consumed &#x2265;1 serving/wk of blueberries, with mean total anthocyanin intake of 11.2 mg/d. Compared to no blueberry intake, women consuming 1-3 servings/mo, 1 serving/wk, and &#x2265;2 servings/wk had corresponding multivariable HRs of total AMD of 0.90 (95% CI: 0.73, 1.11), 0.71 (95% CI: 0.50, 1.00), and 0.36 (95% CI: 0.14, 0.93) (Ptrend = 0.011); those consuming &#x2265;1 servings/wk had an HR of 0.68 (95% CI: 0.47, 0.98). A similar magnitude of HRs were found for visually significant AMD (Ptrend = 0.012) but not for cataract. There were no significant associations between increasing total anthocyanin quintiles and total and visually significant AMD, but there was a modest inverse association with cataract (Ptrend = 0.022), driven by a 10% reduction in cataract in the upper 2 quintiles.<br><br>CONCLUSIONS: Greater blueberry intake significantly reduced total AMD, but not visually significant AMD or cataract. However, the magnitude of effect for visually significant AMD was similar to total AMD. There was a modest but significant inverse association between dietary anthocyanin intake with cataract but not AMD.},
}
@article {pmid38431596,
year = {2024},
author = {Khaboushan, AS and Ebadpour, N and Moghadam, MMJ and Rezaee, Z and Kajbafzadeh, AM and Zolbin, MM},
title = {Cell therapy for retinal degenerative disorders: a systematic review and three-level meta-analysis.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {227},
pmid = {38431596},
issn = {1479-5876},
mesh = {Humans ; *Retina ; *Macular Degeneration/therapy ; Visual Acuity ; Cell- and Tissue-Based Therapy ; },
abstract = {BACKGROUND: Retinal degenerative disorders (RDDs) cause vision loss by damaging retinal neurons and photoreceptors, affecting individuals of all ages. Cell-based therapy has emerged as an effective approach for the treatment of RDDs with promising results. This meta-analysis aims to comprehensively evaluate the efficacy of cell therapy in treating age-related macular degeneration (AMD), retinitis pigmentosa (RP), and Stargardt macular degeneration (SMD) as the most prevalent RDDs.<br><br>METHODS: PubMed, Scopus, Web of Science, and Embase were searched using keywords related to various retinal diseases and cell therapy treatments until November 25th, 2023. The studies' quality was evaluated using the Joanna Briggs Institute's (JBI) checklist for quasi-experimental studies. Visual acuity measured as LogMAR score was used as our main outcome. A three-level random-effect meta-analysis was used to explore the visual acuity in patients who received cell-based therapy. Heterogeneity among the included studies was evaluated using subgroup and sensitivity analyses. Moreover, meta-regression for the type of cells, year of publication, and mean age of participants were performed.<br><br>RESULTS: Overall, 8345 studies were retrieved by the search, and 39 met the eligibility criteria, out of which 18 studies with a total of 224 eyes were included in the meta-analysis. There were 12 studies conducted on AMD, 7 on SMD, and 2 on RP. Cell therapy for AMD showed significant improvement in LogMAR (p&#x2009;<&#x2009;0.05). Also, cell therapy decreased the LogMAR score in SMD and RP (p&#x2009;<&#x2009;0.01 and p&#x2009;<&#x2009;0.0001, respectively). Across all conditions, no substantial publication bias was detected (p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: The findings of the study highlight that the application of cell therapy can enhance the visual acuity in AMD, SMD, and RP.},
}
@article {pmid38431298,
year = {2024},
author = {Li, Q and Tan, J and Xie, H and Zhang, X and Dai, Q and Li, Z and Yan, LL and Chen, W},
title = {Evaluating the accuracy of the Ophthalmologist Robot for multiple blindness-causing eye diseases: a multicentre, prospective study protocol.},
journal = {BMJ open},
volume = {14},
number = {3},
pages = {e077859},
pmid = {38431298},
issn = {2044-6055},
mesh = {Humans ; *Ophthalmologists ; Prospective Studies ; Artificial Intelligence ; *Robotics ; Blindness/diagnosis/etiology ; *Keratitis ; *Corneal Injuries ; *Diabetic Retinopathy/diagnosis ; Multicenter Studies as Topic ; },
abstract = {INTRODUCTION: Early eye screening and treatment can reduce the incidence of blindness by detecting and addressing eye diseases at an early stage. The Ophthalmologist Robot is an automated device that can simultaneously capture ocular surface and fundus images without the need for ophthalmologists, making it highly suitable for primary application. However, the accuracy of the device's screening capabilities requires further validation. This study aims to evaluate and compare the screening accuracies of ophthalmologists and deep learning models using images captured by the Ophthalmologist Robot, in order to identify a screening method that is both highly accurate and cost-effective. Our findings may provide valuable insights into the potential applications of remote eye screening.<br><br>METHODS AND ANALYSIS: This is a multicentre, prospective study that will recruit approximately 1578 participants from 3 hospitals. All participants will undergo ocular surface and fundus images taken by the Ophthalmologist Robot. Additionally, 695 participants will have their ocular surface imaged with a slit lamp. Relevant information from outpatient medical records will be collected. The primary objective is to evaluate the accuracy of ophthalmologists' screening for multiple blindness-causing eye diseases using device images through receiver operating characteristic curve analysis. The targeted diseases include keratitis, corneal scar, cataract, diabetic retinopathy, age-related macular degeneration, glaucomatous optic neuropathy and pathological myopia. The secondary objective is to assess the accuracy of deep learning models in disease screening. Furthermore, the study aims to compare the consistency between the Ophthalmologist Robot and the slit lamp in screening for keratitis and corneal scar using the Kappa test. Additionally, the cost-effectiveness of three eye screening methods, based on non-telemedicine screening, ophthalmologist-telemedicine screening and artificial intelligence-telemedicine screening, will be assessed by constructing Markov models.<br><br>ETHICS AND DISSEMINATION: The study has obtained approval from the ethics committee of the Ophthalmology and Optometry Hospital of Wenzhou Medical University (reference: 2023-026&#x2009;K-21-01). This work will be disseminated by peer-review publications, abstract presentations at national and international conferences and data sharing with other researchers.<br><br>TRIAL REGISTRATION NUMBER: ChiCTR2300070082.},
}
@article {pmid38428785,
year = {2024},
author = {Shen, X and Zhou, T and Sun, Z and Zheng, Y and Lin, B and Huang, Y},
title = {Trends in application of fundus fluorescein angiography in fundus diseases during a recent ten-year period.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {46},
number = {},
pages = {104029},
doi = {10.1016/j.pdpdt.2024.104029},
pmid = {38428785},
issn = {1873-1597},
mesh = {Humans ; *Fluorescein Angiography/methods ; Retrospective Studies ; Female ; Male ; Retinal Diseases/diagnostic imaging ; Middle Aged ; Fundus Oculi ; Adult ; Aged ; China/epidemiology ; },
abstract = {PURPOSE: To analyze the trends in the application of fundus fluorescein angiography (FFA) in fundus diseases over ten years.<br><br>METHOD: It was a retrospective study. Patients who underwent FFA examinations between Jan 2012 and Dec 2021 in Eye Hospital of Wenzhou Medical University were included, excluding infants. Data included the fundus disease and examination time of FFA.<br><br>RESULTS: A total of 37,038 cases underwent FFA examinations in our hospital in the past decade, and the number of each year was 3,628, 2,232, 2,230, 2,351, 3,546, 3,924, 5,325, 4,202, 4,432 and 5,168 from 2012 to 2021, respectively. The top three diseases were central serous chorioretinopathy (CSC), diabetic retinopathy (DR) and retinal vein occlusion (RVO) over the years from 2012 to 2021. The fourth to eighth ranked diseases were uveitis, age-related macular degeneration (AMD), choroidal neovascularization (CNV), optic neuropathy (ON) and polypoid choroidal vasculopathy (PCV) 9 years from 2012 to 2020; while retinal artery occlusion (RAO) ranked eighth and PCV fell out of the first eight in 2021. Tumor, Eale's disease, macular hemorrhage (MH), epiretinal retinal membrane (ERM) and Coat's disease had consistent proportions over the years. There was a significant statistical difference in the proportion of disease components over the years from 2012 to 2021(p = 0.000).<br><br>CONCLUSION: Despite changes in annual distribution, CSC, DR, and RVO consistently ranked as the top three diseases requiring FFA examination. Changes might be related to the development of non-invasive fundus examination instruments and technologies. Indicated that FFA still hold its irreplaceable nature in diagnosing and understanding fundus diseases.},
}
@article {pmid38428557,
year = {2024},
author = {Haj Najeeb, B and Gerendas, BS and Deak, GG and Leingang, O and Bogunovic, H and Schmidt-Erfurth, U},
title = {An Automated Comparative Analysis of the Exudative Biomarkers in Neovascular Age-Related Macular Degeneration, The RAP Study: Report 6.},
journal = {American journal of ophthalmology},
volume = {264},
number = {},
pages = {53-65},
doi = {10.1016/j.ajo.2024.02.018},
pmid = {38428557},
issn = {1879-1891},
mesh = {Humans ; Cross-Sectional Studies ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/metabolism ; Female ; Male ; *Biomarkers/metabolism ; *Subretinal Fluid/metabolism ; Aged ; Aged, 80 and over ; Fluorescein Angiography/methods ; Artificial Intelligence ; Visual Acuity/physiology ; },
abstract = {PURPOSE: To investigate differences in volume and distribution of the main exudative biomarkers across all types and subtypes of macular neovascularization (MNV) using artificial intelligence (AI).<br><br>DESIGN: Cross-sectional study.<br><br>METHODS: An AI-based analysis was conducted on 34,528 OCT B-scans consisting of 281 (250 unifocal, 31 multifocal) MNV3, 55 MNV2, and 121 (30 polypoidal, 91 non-polypoidal) MNV1 treatment-naive eyes. Means (SDs), medians and heat maps of cystic intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED), and hyperreflective foci (HRF) volumes, as well as retinal thickness (RT) were compared among MNV types and subtypes.<br><br>RESULTS: MNV3 had the highest mean IRF with 291 (290) nL, RT with 357 (49) &#xb5;m, and HRF with 80 (70) nL, P &#x2264; .05. MNV1 showed the greatest mean SRF with 492 (586) nL, whereas MNV3 exhibited the lowest with 218 (382) nL, P &#x2264; .05. Heat maps showed IRF confined to the center, whereas SRF was scattered in all types. SRF, HRF, and PED were more distributed in the temporal macular half in MNV3. Means of IRF, HRF, and PED were higher in the multifocal than in the unifocal MNV3 with 416 (309) nL,114 (95) nL, and 810 (850) nL, P &#x2264; .05. Compared to the non-polypoidal subtype, the polypoidal subtype had greater means of SRF with 695 (718) nL, HRF 69 (63) nL, RT 357 (45) &#xb5;m, and PED 1115 (1170) nL, P &#x2264; .05.<br><br>CONCLUSIONS: This novel quantitative AI analysis shows that SRF is a biomarker of choroidal origin in MNV1, whereas IRF, HRF, and RT are retinal biomarkers in MNV3. Polypoidal MNV1 and multifocal MNV3 present with higher exudation compared to other subtypes.},
}
@article {pmid38428459,
year = {2024},
author = {Karkhaneh, R and Faghihi, H and Riazi-Esfahani, H and Abrishami, M and Bazvand, F and Ebrahimiadib, N and Johari, M and Akhlaghi, M and Shoeibi, N and Nowroozzadeh, MH and Ansari Astaneh, MR and Khojasteh, H and Imani Fooladi, M and Khodabande, A and Ghassemi, F and Khalili Pour, E and Zarei, M and Mirshahi, A and Fazel, F and Ashraf, H and Hosseini, SM and Dourandeesh, M and Feghhi, M and Alizadeh, Y and Behboudi, H and Azadi, P and Sabzvari, A and Kafi, H and Ghasemi Falavarjani, K},
title = {Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {8},
pages = {744-753},
doi = {10.1016/j.oret.2024.02.012},
pmid = {38428459},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Biosimilar Pharmaceuticals/administration &amp; dosage/adverse effects/therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Fluorescein Angiography/methods ; Follow-Up Studies ; Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {OBJECTIVE: To assess the noninferiority of biosimilar aflibercept (P041, CinnaGen) to the originator aflibercept (AFL, Regeneron) in terms of efficacy, safety, and immunogenicity.<br><br>DESIGN: This was a phase &#x428;, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio.<br><br>SUBJECTS: Patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the 2 groups of P041 and AFL.<br><br>METHODS: Patients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week&#xa0;48.<br><br>MAIN OUTCOME MEASURES: The primary outcome was the noninferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity during the study.<br><br>RESULTS: In total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in the P041 group compared with 94.52% in the AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference,&#xa0;-0.0008; 95% CI,&#xa0;-0.074 to 0.074; P&#xa0;= 0.98). Secondary outcomes indicated similar results in both arms (all P > 0.05). Safety measured outcomes and immunogenicity were similar between the 2 study groups.<br><br>CONCLUSIONS: Biosimilar aflibercept was noninferior to AFL in eyes with neovascular age-related macular degeneration. Other efficacy and safety findings also indicated the similarity of 2 products.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38427348,
year = {2024},
author = {Hogg, RE and Wickens, R and O'Connor, S and Gidman, E and Ward, E and Peto, T and Burton, BJL and Knox, P and Lotery, AJ and Sivaprasad, S and Donnelly, M and Rogers, CA and Reeves, BC},
title = {Inequalities in Uptake and Use of Digital Applications for Home-Monitoring of Neovascular Age-Related Macular Degeneration in an Elderly Visually Impaired Population: The MONARCH Study.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {3},
pages = {2},
pmid = {38427348},
issn = {2164-2591},
mesh = {Humans ; Aged ; *Choroidal Neovascularization ; Visual Acuity ; *Telemedicine ; *Macular Degeneration/diagnosis/epidemiology ; },
abstract = {PURPOSE: To describe inequalities in the Monitoring for Neovascular Age-related Macular Degeneration Reactivation at Home (MONARCH) diagnostic test accuracy study for: recruitment; participants' ability to self-test; and adherence to testing using digital applications during follow-up.<br><br>METHODS: Home-monitoring vision tests included two tests implemented as software applications (apps: MyVisionTrack and MultiBit) on an iPod Touch device. Patients were provided with all hardware required to participate (iPod and MIFI device) and trained to use the apps. Regression models estimated associations of age, sex, Index of Multiple Deprivation, strata of time since first diagnosis, and baseline visual acuity at study entry on outcomes of willingness to participate, ability to perform tests, and adherence to weekly testing.<br><br>RESULTS: A minority of patients who were approached were willing-in-principle to participate. Increasing age was associated with being unwilling-in-principle to participate. Patients from the most deprived areas had a 47% decrease in odds of being willing compared to those from the middle quintile deprived areas (odds ratio, 0.53; 95% confidence interval = 0.32, 0.88). Increasing age and worse deprivation were not consistently associated either with ability to self-monitor with the index tests, or adherence to weekly testing.<br><br>CONCLUSIONS: Associations of increasing age and worse deprivation index were associated with unwillingness-in-principle to participate despite the provision of hardware' highlighting the potential for inequality with interventions of the kind evaluated.<br><br>TRANSLATIONAL RELEVANCE: The clear evidence of inequalities in participation should prompt future research on ways to encourage adoption of mobile health technologies by underserved populations.},
}
@article {pmid38427135,
year = {2024},
author = {Pereira, PN and Simão, J and Silva, CS and Farinha, C and Murta, J and Silva, R},
title = {Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {122},
pmid = {38427135},
issn = {1573-2630},
mesh = {Aged ; Aged, 80 and over ; Humans ; Middle Aged ; Atrophy/complications/pathology ; Choroid/pathology ; *Choroidal Neovascularization/diagnosis/pathology ; Coloring Agents ; Fluorescein Angiography/methods ; Indocyanine Green ; *Polypoidal Choroidal Vasculopathy/diagnostic imaging ; Retrospective Studies ; Tomography, Optical Coherence/methods ; },
abstract = {INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV.<br><br>METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants.<br><br>RESULTS: Fifty-five patients (median age, 74&#x2009;&#xb1;&#x2009;15&#xa0;years) were included. After 15.5&#x2009;&#xb1;&#x2009;6.4&#xa0;months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases.<br><br>CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.},
}
@article {pmid38425149,
year = {2024},
author = {Munzar, R and Roh, S and Ramsey, DJ},
title = {Factors associated with loss to follow-up in patients with advanced age-related macular degeneration: A telehealth recall initiative.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {44},
number = {3},
pages = {626-633},
doi = {10.1111/opo.13298},
pmid = {38425149},
issn = {1475-1313},
support = {//Association for Research in Vision and Ophthalmology/ ; //Beth Israel Lahey Health/ ; },
mesh = {Humans ; *Macular Degeneration/therapy/complications ; Visual Acuity ; Follow-Up Studies ; *Geographic Atrophy/complications ; *Telemedicine ; },
abstract = {INTRODUCTION: Patients with advanced age-related macular degeneration (AMD) frequently experience loss to follow-up (LTFU), heightening the risk of vision loss from treatment delays. This study aimed to identify factors contributing to LTFU in patients with advanced AMD and assess the effectiveness of telephone-based outreach in reconnecting them with eye care.<br><br>METHODS: A custom reporting tool identified patients with advanced AMD who had not returned for eye care between 31 October 2021 and 1 November 2022. Potentially LTFU patients were enrolled in a telephone outreach programme conducted by a telehealth extender to encourage their return for care. Linear regression analysis identified factors associated with being LTFU and likelihood of accepting care post-outreach.<br><br>RESULTS: Out of 1269 patients with advanced AMD, 105 (8.3%) did not return for recommended eye care. Patients LTFU were generally older (89.2&#x2009;&#xb1;&#x2009;8.9&#x2009;years vs. 87.2&#x2009;&#xb1;&#x2009;8.5&#x2009;years, p&#x2009;=&#x2009;0.02) and lived farther from the clinic (25&#x2009;&#xb1;&#x2009;43&#x2009;miles vs. 17&#x2009;&#xb1;&#x2009;30&#x2009;miles, p&#x2009;=&#x2009;0.009). They also had a higher rate of advanced dry AMD (26.7% vs. 18.5%, p&#x2009;=&#x2009;0.04) and experienced worse vision in both their better-seeing (0.683 logMAR vs. 0.566 logMAR, p&#x2009;=&#x2009;0.03) and worse-seeing (1.388 logMAR vs. 1.235 logMAR, p&#x2009;=&#x2009;0.04) eyes. Outreach by a telehealth extender reached 62 patients (59%), 43 through family members or healthcare proxies. Half of the cases where a proxy was contacted revealed that the patient in question had died. Among those contacted directly, one third expressed willingness to resume eye care (20 patients), with 11 scheduling appointments (55%). Despite only two patients returning for in-person eye care through the intervention, the LTFU rate halved to 4.4% by accounting for those patients who no longer needed eye care at the practice.<br><br>CONCLUSIONS: There is a substantial risk that older patients with advanced AMD will become LTFU. Targeted telephone outreach can provide a pathway for vulnerable patients to return to care.},
}
@article {pmid38423204,
year = {2024},
author = {Wang, L and Wei, W and Zhao, Y and Chen, S and Wu, D and Tu, M},
title = {Causal associations of refractive error and early age-related macular degeneration: A Mendelian randomization study.},
journal = {Experimental eye research},
volume = {241},
number = {},
pages = {109850},
doi = {10.1016/j.exer.2024.109850},
pmid = {38423204},
issn = {1096-0007},
mesh = {Humans ; Genome-Wide Association Study ; *Hyperopia ; *Macular Degeneration/genetics ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; *Refractive Errors/genetics ; Meta-Analysis as Topic ; },
abstract = {This study aims to determine the risk associated with early age-related macular degeneration (AMD) due to refractive errors (RE) using an analysis of genome-wide association study (GWAS) data through the two-sample Mendelian randomization approach. Single-nucleotide polymorphisms (SNPs) linked to refractive errors (RE) were obtained from numerous GWAS studies involving individuals of European descent. The data for early AMD was obtained from a diverse, multiethnic GWAS meta-analysis that included 105,248 participants (14,034 cases and 91,214 controls). The primary outcome measure focused on the rise in early AMD risk corresponding to a 1-diopter alteration in spherical power and cylindrical power. In the main Mendelian randomization analysis, inverse-variance weighting (IVW) methods were applied for the evaluation. Mendelian Randomization (MR) study revealed a substantial impact of refractive error (RE) on early AMD risk, with a 1-diopter increase in hypermetropia being related to a 1.16 odds ratio (OR) for a greater risk of early AMD (95% CI, 1.10-1.23; P < 0.01). This conclusion was further supported by four supplementary approaches, namely, Weighted mode, Weighted-median, Simple mode, and MR-Egger. The results suggest a heightened risk of early AMD correlated with hyperopia, necessitating further research to thoroughly elucidate this potential causal relationship.},
}
@article {pmid38421937,
year = {2024},
author = {Vakharia, P and Eichenbaum, D},
title = {Geographic atrophy: current and future therapeutic agents and practical considerations for retinal specialists.},
journal = {Current opinion in ophthalmology},
volume = {35},
number = {3},
pages = {165-169},
doi = {10.1097/ICU.0000000000001046},
pmid = {38421937},
issn = {1531-7021},
mesh = {Humans ; *Geographic Atrophy/drug therapy ; Retina ; *Macular Degeneration/drug therapy ; Vision Disorders ; Inflammation/drug therapy ; Intravitreal Injections ; },
abstract = {PURPOSE OF REVIEW: Geographic atrophy (GA) from age-related macular degeneration (AMD) remains a leading cause of vision loss. The purpose of this review is to summarize currently available intravitreal therapeutics, and discuss pipeline therapeutics that are currently in clinical trials.<br><br>RECENT FINDINGS: The FDA approval of pegcetacoplan and avacincaptad pegol, both approved in 2023, represent the first therapeutics to treat GA. These are delivered via intravitreal injections, and have been shown to slow progression of GA. Both drugs have a risk of new onset neovascular age-related macular degeneration (nAMD). Initial indications seem to be that pegcetacoplan therapy has higher risks of inflammation, vasculitis, and nonarteritic ischemic optic neuropathy (NAION) as compared to avacincaptad pegol, but more real-world data will help to clarify this further. Pipeline therapeutics that we discuss include intravitreal gene therapy, oral anticomplement therapy, and intravitreal injections of a novel glycoprotein.<br><br>SUMMARY: Both pegcetacoplan and avacincaptad pegol are FDA approved to treat GA. The decision to treat patients is still complex and nuanced, but the approval of two treatments for GA is a tremendous advance in our field. Future therapeutics may further refine our ability to treat patients more effectively and safely.},
}
@article {pmid38421861,
year = {2024},
author = {Thangamathesvaran, L and Kong, J and Bressler, SB and Singh, M and Wenick, AS and Scott, AW and Arévalo, JF and Bressler, NM},
title = {Severe Intraocular Inflammation Following Intravitreal Faricimab.},
journal = {JAMA ophthalmology},
volume = {142},
number = {4},
pages = {365-370},
pmid = {38421861},
issn = {2168-6173},
mesh = {Humans ; Bevacizumab/therapeutic use ; *Uveitis/drug therapy ; Inflammation/drug therapy ; Intravitreal Injections ; *Uveal Diseases/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; *Antibodies, Bispecific ; },
abstract = {IMPORTANCE: Monitoring for and reporting potential cases of intraocular inflammation (IOI) in clinical practice despite limited occurrences in clinical trials, including experiences with relatively new intravitreal agents, such as brolucizumab, pegcetacoplan, or faricimab, helps balance potential benefits and risks of these agents.<br><br>OBJECTIVE: To provide descriptions of 3 initially culture-negative cases of acute, severe, posterior-segment IOI events occurring within the same month following intravitreal faricimab injections at a single institution.<br><br>In this case series, 3 patients manifesting acute, severe IOI following intravitreal injection of faricimab were identified between September 20, 2023, and October 20, 2023.<br><br>EXPOSURE: Faricimab, 6 mg (0.05 mL of 120 mg/mL solution), for neovascular age-related macular degeneration among patients previously treated with aflibercept; 1 patient also had prior exposure to bevacizumab.<br><br>MAIN OUTCOMES AND MEASURES: Visual acuity, vitreous taps for bacterial or fungal cultures, and retinal imaging.<br><br>RESULTS: All 3 patients received intravitreal faricimab injections between September 20 and October 20, 2023, from 2 different lot numbers (expiration dates, July 2025) at 3 locations of 1 institution among 3 of 19 retina physicians. Visual acuities with correction were 20/63 OS for patient 1, 20/40 OD for patient 2, and 20/20 OS for patient 3 prior to injection. All 3 patients developed acute, severe inflammation involving the anterior and posterior segment within 3 to 4 days after injection, with visual acuities of hand motion OS, counting fingers OD, and hand motion OS, respectively. Two patients were continuing faricimab treatment while 1 patient was initiating faricimab treatment. All received intravitreal ceftazidime, 2.2 mg/0.1 mL, and vancomycin, 1 mg/0.1 mL, immediately following vitreous taps. All vitreous tap culture results were negative. One patient underwent vitrectomy 1 day following presentation. Intraoperative vitreous culture grew 1 colony of Staphylococcus epidermidis, judged a likely contaminant by infectious disease specialists. All symptoms resolved within 1 month; visual acuities with correction were 20/100 OS for patient 1, 20/50 OD for patient 2, and 20/30 OS for patient 3.<br><br>CONCLUSIONS AND RELEVANCE: In this case series, 3 patients with acute, severe IOI within 1 month at 3 different locations among 3 ophthalmologists of 1 institution following intravitreal faricimab could represent some unknown storage or handling problem. However, this cluster suggests such inflammatory events may be more common than anticipated from faricimab trial reports, emphasizing the continued need for vigilance to detect and report such cases following regulatory approval.},
}
@article {pmid38421833,
year = {2024},
author = {Warner, EF and Vaux, L and Boyd, K and Widdowson, PS and Binley, KM and Osborne, A},
title = {Ocular delivery of Pigment Epithelium-Derived Factor (PEDF) as a neuroprotectant for Geographic Atrophy.},
journal = {Aging and disease},
volume = {15},
number = {5},
pages = {2003-2007},
pmid = {38421833},
issn = {2152-5250},
mesh = {Animals ; Humans ; *Eye Proteins/metabolism/therapeutic use/administration &amp; dosage/genetics/pharmacology ; Genetic Therapy/methods ; Genetic Vectors/administration &amp; dosage ; *Geographic Atrophy/drug therapy/metabolism ; *Nerve Growth Factors/administration &amp; dosage/therapeutic use ; Neuroprotective Agents/therapeutic use/administration &amp; dosage/pharmacology ; *Serpins/administration &amp; dosage/therapeutic use/genetics/metabolism/pharmacology ; },
abstract = {Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD), that starts with atrophic lesions in the outer retina that expand to cover the macula and fovea, leading to severe vision loss over time. Pigment Epithelium-Derived Factor (PEDF) has a diverse-range of properties, including its ability to promote cell survival, reduce inflammation, inhibit angiogenesis, combat oxidative stress, regulate autophagy, and stimulate anti-apoptotic pathways, making it a promising therapeutic candidate for GA. However, the relatively short half-life of PEDF protein has precluded its potential as a clinical therapy for GA since it would require frequent injections. Therefore, we describe administration of a PEDF gene, comparing and contrasting delivery routes, viral and non-viral vectors, and consider the critical challenges for PEDF as a neuroprotectant for GA.},
}
@article {pmid38421830,
year = {2024},
author = {Buonfiglio, F and Korb, CA and Stoffelns, B and Pfeiffer, N and Gericke, A},
title = {Recent Advances in Our Understanding of Age-Related Macular Degeneration: Mitochondrial Dysfunction, Redox Signaling, and the Complement System.},
journal = {Aging and disease},
volume = {16},
number = {3},
pages = {1535-1575},
pmid = {38421830},
issn = {2152-5250},
mesh = {Humans ; *Macular Degeneration/metabolism/pathology ; *Mitochondria/metabolism/pathology ; Oxidative Stress ; Oxidation-Reduction ; Signal Transduction ; *Complement System Proteins/metabolism ; Aging ; Animals ; Complement Activation ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent degenerative disorder of the central retina, which holds global significance as the fourth leading cause of blindness. The condition is characterized by a multifaceted pathophysiology that involves aging, oxidative stress, inflammation, vascular dysfunction, and complement activation. The complex interplay of these factors contributes to the initiation and progression of AMD. Current treatments primarily address choroidal neovascularization (CNV) in neovascular AMD. However, the approval of novel drug therapies for the atrophic and more gradual variant, known as geographic atrophy (GA), has recently occurred. In light of the substantial impact of AMD on affected individuals' quality of life and the strain it places on healthcare systems, there is a pressing need for innovative medications. This paper aims to provide an updated and comprehensive overview of advancements in our understanding of the etiopathogenesis of AMD. Special attention will be given to the influence of aging and altered redox status on mitochondrial dynamics, cell death pathways, and the intricate interplay between oxidative stress and the complement system, specifically in the context of GA. Additionally, this review will shed light on newly approved therapies and explore emerging alternative treatment strategies in the field. The objective is to contribute to the ongoing dialogue surrounding AMD, offering insights into the latest developments that may pave the way for more effective management and intervention approaches.},
}
@article {pmid38421486,
year = {2025},
author = {Tang, H and Wei, W and Luo, Y and Lu, X and Chen, J and Yang, S and Wu, F and Zhou, H and Ma, W and Yang, X},
title = {P2X7 receptors: a bibliometric review from 2002 to 2023.},
journal = {Purinergic signalling},
volume = {21},
number = {4},
pages = {959-977},
pmid = {38421486},
issn = {1573-9546},
mesh = {*Receptors, Purinergic P2X7/metabolism ; Humans ; *Bibliometrics ; Animals ; },
abstract = {For many years, there has been ongoing research on the P2X7 receptor (P2X7R). A comprehensive, systematic, and objective evaluation of the scientific output and status of P2X7R will be instrumental in guiding future research directions. This study aims to present the status and trends of P2X7R research from 2002 to 2023. Publications related to P2X7R were retrieved from the Web of Science Core Collection database. Quantitative analysis and visualization tools were Microsoft Excel, VOSviewer, and CiteSpace software. The analysis content included publication trends, literature co-citation, and keywords. 3282 records were included in total, with the majority of papers published within the last 10 years. Based on literature co-citation and keyword analysis, neuroinflammation, neuropathic pain, gastrointestinal diseases, tumor microenvironment, rheumatoid arthritis, age-related macular degeneration, and P2X7R antagonists were considered to be the hotspots and frontiers of P2X7R research. Researchers will get a more intuitive understanding of the status and trends of P2X7R research from this study.},
}
@article {pmid38418207,
year = {2024},
author = {Park, J and Jung, W and Han, K and Kim, B and Lee, SY and Yoon, JM and Lim, DH and Shin, DW},
title = {Association between age-related macular degeneration and risk of incident cancer.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {9},
pages = {1249-1256},
doi = {10.1136/bjo-2023-323874},
pmid = {38418207},
issn = {1468-2079},
mesh = {Humans ; Female ; Male ; Incidence ; *Macular Degeneration/epidemiology ; Risk Factors ; Republic of Korea/epidemiology ; Aged ; Middle Aged ; *Neoplasms/epidemiology ; Follow-Up Studies ; Retrospective Studies ; Risk Assessment/methods ; Databases, Factual ; Visual Acuity/physiology ; },
abstract = {BACKGROUND/AIMS: Age-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD with visual disability (VD) status.<br><br>METHODS: This was a population-based cohort study using data from the Korean National Health Insurance Service database (2009-2019) including patients who participated in a national health screening programme in 2009. The subjects were categorised based on the presence of AMD and VD. The occurrence of cancer was identified using principal diagnosis according to the International Classification of Disease, 10th revision codes in claims data. The Cox regression hazard model was used to compare HRs of site-specific cancer.<br><br>RESULTS: Among 4 088 814 participants, 51 596 had AMD of which 3683 subjects had VD. The mean follow-up period was 9.6 years. The overall cancer risk was generally null, but the risk of hypervascular cancer such as thyroid cancer (adjusted HR (aHR) 1.10, 95% CI 1.00 to 1.20) and renal cancer (aHR 1.16, 95% CI 1.00 to 1.33) was higher and the risk of stomach cancer (aHR 0.89, 95% CI 0.84 to 0.94) was lower in the AMD group than in the non-AMD group.<br><br>CONCLUSION: This study demonstrated a possible association between AMD and several cancers. Increased renal and thyroid cancer risk among patients with AMD could indicate that AMD is associated with hypervascular cancer. Further studies in which additional databases are used and the underlying detailed mechanisms evaluated are needed to validate our results.},
}
@article {pmid38417110,
year = {2024},
author = {Klymenko, V and González Martínez, OG and Zarbin, MA},
title = {Recent Progress in Photoreceptor Cell-Based Therapy for Degenerative Retinal Disease.},
journal = {Stem cells translational medicine},
volume = {13},
number = {4},
pages = {332-345},
pmid = {38417110},
issn = {2157-6580},
mesh = {Humans ; *Retinal Degeneration/therapy ; Retina ; *Macular Degeneration/therapy ; Photoreceptor Cells ; Cell- and Tissue-Based Therapy ; Stem Cell Transplantation/methods ; },
abstract = {Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving transplantation of photoreceptors as treatment for these conditions are underway. In this review, we summarize recent progress in the field of photoreceptor transplantation, including some pertinent results regarding photoreceptor manufacture, photoreceptor transplantation, mechanisms of donor-host cell integration such as material transfer and photoreceptor transplant immunology. We conclude by proposing several approaches that may provide a rational basis for selecting a vision restoration strategy (eg, donor-host synapse formation vs donor-host nanotube formation) and improved transplant efficiency.},
}
@article {pmid38416457,
year = {2024},
author = {Navneet, S and Wilson, K and Rohrer, B},
title = {Müller Glial Cells in the Macula: Their Activation and Cell-Cell Interactions in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {2},
pages = {42},
pmid = {38416457},
issn = {1552-5783},
support = {I01 BX003050/BX/BLRD VA/United States ; I01 RX000444/RX/RRD VA/United States ; IK6 BX004858/BX/BLRD VA/United States ; R01 EY030072/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Ependymoglial Cells ; *Macula Lutea ; Retina ; Cell Communication ; *Wet Macular Degeneration ; *Geographic Atrophy ; },
abstract = {Müller glia, the main glial cell of the retina, are critical for neuronal and vascular homeostasis in the retina. During age-related macular degeneration (AMD) pathogenesis, Müller glial activation, remodeling, and migrations are reported in the areas of retinal pigment epithelial (RPE) degeneration, photoreceptor loss, and choroidal neovascularization (CNV) lesions. Despite this evidence indicating glial activation localized to the regions of AMD pathogenesis, it is unclear whether these glial responses contribute to AMD pathology or occur merely as a bystander effect. In this review, we summarize how Müller glia are affected in AMD retinas and share a prospect on how Müller glial stress might directly contribute to the pathogenesis of AMD. The goal of this review is to highlight the need for future studies investigating the Müller cell's role in AMD. This may lead to a better understanding of AMD pathology, including the conversion from dry to wet AMD, which has no effective therapy currently and may shed light on drug intolerance and resistance to current treatments.},
}
@article {pmid38416238,
year = {2024},
author = {Cnaany, Y and Lender, R and Chowers, I and Tiosano, L and Shwartz, Y and Levy, J},
title = {An automated process for bulk downloading optical coherence tomography scans.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {7},
pages = {2145-2151},
pmid = {38416238},
issn = {1435-702X},
support = {#3485/19//Ministry of Science and Technology, Israel/ ; },
mesh = {*Tomography, Optical Coherence/methods ; Humans ; Retina/diagnostic imaging ; Macular Degeneration/diagnosis ; Retrospective Studies ; Male ; },
abstract = {OBJECTIVE: To develop an automated method for efficiently downloading a large number of optical coherence tomography (OCT) scans obtained using the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) platform.<br><br>METHODS: The electronic medical records and OCT scans were extracted for all patients with age-related macular degeneration treated at the Hadassah University Hospital Retina Clinic between 2010 and 2021. A macro was created using Visual Basic for Applications (VBA) and Microsoft Excel to automate the export process and anonymize the OCT scans in accordance with hospital policy. OCT scans were extracted as proprietary Heidelberg E2E files.<br><br>RESULTS: The VBA macro was used to export a total of 94,789 E2E files from 2807 patient records, with an average processing time of 4.32 min per volume scan (SD: 3.57 min). The entire export process took a total of approximately 202 h to complete over a period of 24 days. In a smaller sample, using the macro to download the scans was significantly faster than manually downloading the scans, averaging 3.88 vs. 11.08 min/file, respectively (t&#x2009;=&#x2009;8.59, p&#x2009;<&#x2009;0.001). Finally, we found that exporting the files during both off-clinic and working hours resulted in significantly faster processing times compared to exporting the files solely during working hours (t&#x2009;=&#x2009;5.77, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: This study demonstrates the feasibility of using VBA and Excel to automate the process for bulk downloading data from a specific medical imaging platform. The specific steps and techniques will likely vary depending on the software used and hospital constraints and should be determined for each application.},
}
@article {pmid38416237,
year = {2024},
author = {Schneider, M and Bjerager, J and Hodzic-Hadzibegovic, D and Klefter, ON and Subhi, Y and Hajari, J},
title = {Short-term outcomes of treatment switch to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {7},
pages = {2153-2162},
pmid = {38416237},
issn = {1435-702X},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Drug Resistance ; *Drug Substitution ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; *Intravitreal Injections ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors ; Recombinant Fusion Proteins/administration &amp; dosage ; Retrospective Studies ; Time Factors ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Antibodies, Bispecific/administration &amp; dosage ; },
abstract = {PURPOSE: To report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD).<br><br>METHODS: Single-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023.<br><br>RESULTS: A total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference:&#x2009;-&#x2009;31&#xa0;&#x3bc;m, IQR: 55, p&#x2009;<&#x2009;0.0001 and median difference:&#x2009;-&#x2009;21&#xa0;&#x3bc;m, IQR: 36, p&#x2009;<&#x2009;0.0001, respectively) and a statistically significant increase in CRT (median difference:&#x2009;+&#x2009;19&#xa0;&#x3bc;m, IQR: 20, p&#x2009;=&#x2009;0.0143) and no change in PED height (median difference:&#x2009;+&#x2009;22&#xa0;&#x3bc;m, IQR: 64, p&#x2009;=&#x2009;0.1508) in those that did not. Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed.<br><br>CONCLUSIONS: Our findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation.<br><br>STUDY REGISTRATION: ClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.},
}
@article {pmid38415914,
year = {2024},
author = {Sridevi Gurubaran, I},
title = {Mitochondrial damage and clearance in retinal pigment epithelial cells.},
journal = {Acta ophthalmologica},
volume = {102},
number = {3},
pages = {374},
doi = {10.1111/aos.16664},
pmid = {38415914},
issn = {1755-3768},
mesh = {Humans ; *Oxidative Stress ; *Macular Degeneration ; Epithelial Cells ; Retinal Pigments ; Retinal Pigment Epithelium ; },
}
@article {pmid38414529,
year = {2024},
author = {Sun, C and Zhang, S and Xu, N and Liu, K and Wei, F and Zhang, X and Zhang, J and Gao, S and Yu, Y and Ding, X},
title = {Topical Ophthalmic Liposomes Dual-Modified with Penetratin and Hyaluronic Acid for the Noninvasive Treatment of Neovascular Age-Related Macular Degeneration.},
journal = {International journal of nanomedicine},
volume = {19},
number = {},
pages = {1887-1908},
pmid = {38414529},
issn = {1178-2013},
mesh = {Mice ; Animals ; Humans ; Liposomes/therapeutic use ; Angiogenesis Inhibitors/pharmacology ; Hyaluronic Acid ; Vascular Endothelial Growth Factor A ; *Choroidal Neovascularization/drug therapy/metabolism ; *Macular Degeneration/drug therapy ; Ophthalmic Solutions/therapeutic use ; Intravitreal Injections ; *Cell-Penetrating Peptides ; },
abstract = {INTRODUCTION: Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance.<br><br>METHODS: Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue.<br><br>RESULTS: PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 &#xb1; 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection.<br><br>CONCLUSION: PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.},
}
@article {pmid38412525,
year = {2025},
author = {Nivison-Smith, L and Faiza, A and Roy, T and Trinh, M},
title = {Retinal vessel diameters in intermediate age-related macular degeneration using en face optical coherence tomography.},
journal = {Clinical &amp; experimental optometry},
volume = {108},
number = {1},
pages = {27-32},
doi = {10.1080/08164622.2024.2311703},
pmid = {38412525},
issn = {1444-0938},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; Middle Aged ; *Macular Degeneration/diagnosis ; *Retinal Vessels/pathology/diagnostic imaging ; Arterioles/pathology ; Aged, 80 and over ; Venules/pathology ; Reproducibility of Results ; },
abstract = {CLINICAL RELEVANCE: Clinical assessment of age-related macular degeneration (AMD) relies on biomarkers that do not necessarily reflect the contributions of vascular dysfunction. Validation of clinically accessible methods of measuring retinal vascular integrity could provide a more holistic understanding of AMD-related changes to facilitate appropriate care.<br><br>BACKGROUND: There is conflicting evidence if retinal vessel calibre is significantly altered in the early stages of AMD. This study examined the outer and inner diameters of first order retinal vessels in intermediate AMD eyes using en face optical coherence tomography (OCT).<br><br>METHODS: Retinal en face (6&#x2009;&#xd7;&#x2009;6&#x2009;mm) OCT images were examined in a single eye of participants with intermediate AMD (n&#x2009;=&#x2009;46) versus normal macula (n&#x2009;=&#x2009;43) for arterioles (all identifiable) and venules (40/46 and 39/43 identifiable). All participants were aged&#x2009;&#x2265;50&#x2009;years without diabetes mellitus, hypertension, or other systemic vascular disease.<br><br>RESULTS: Intra- and inter-grader agreement was good-to-excellent for all en face OCT measurements of arteriole and venule diameters (intraclass correlation coefficient&#x2009;=&#x2009;0.87 to 0.99). Arteriolar outer diameters (82.3&#x2009;&#xb1;&#x2009;19.8&#x2009;&#xb5;m vs 73.8&#x2009;&#xb1;&#x2009;16.1&#x2009;&#xb5;m; p&#x2009;<&#x2009;0.05) and inner diameters (35.1&#x2009;&#xb1;&#x2009;8.4&#x2009;&#xb5;m vs 31.5&#x2009;&#xb1;&#x2009;8.1&#x2009;&#xb5;m; p&#x2009;<&#x2009;0.05) were significantly greater in AMD eyes compared to normal eyes. Venular inner diameter was significantly greater (43.1&#x2009;&#xb1;&#x2009;9.5&#x2009;&#xb5;m vs 39.2&#x2009;&#xb1;&#x2009;10.1&#x2009;&#xb5;m; p&#x2009;<&#x2009;0.05), but outer diameter remained unchanged (p&#x2009;=&#x2009;0.17) in AMD eyes compared to normal eyes.<br><br>CONCLUSION: Arteriolar dilation and altered venular inner diameter were observed in intermediate AMD eyes. These results support further investigation of vascular contributions to AMD in the early stages of disease, possibly using the en face OCT imaging modality.},
}
@article {pmid38411775,
year = {2024},
author = {Zou, Y and Jiang, J and Li, Y and Ding, X and Fang, F and Chen, L},
title = {Quercetin Regulates Microglia M1/M2 Polarization and Alleviates Retinal Inflammation via ERK/STAT3 Pathway.},
journal = {Inflammation},
volume = {47},
number = {5},
pages = {1616-1633},
pmid = {38411775},
issn = {1573-2576},
support = {81371042//National Natural Science Foundation of China/ ; 22Y11910500//Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission/ ; 202301AY070001-086//Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; 2023J0039//Yunnan Provincial Education Department's Scientific Research Foundation/ ; 202305AC160073//Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; },
mesh = {Animals ; *Microglia/drug effects/metabolism ; *STAT3 Transcription Factor/metabolism ; *Quercetin/pharmacology/therapeutic use ; Mice ; Male ; *Mice, Inbred C57BL ; MAP Kinase Signaling System/drug effects ; Retinitis/drug therapy/metabolism ; Lipopolysaccharides/toxicity ; Retina/drug effects/metabolism/pathology ; Blood-Retinal Barrier/drug effects/metabolism ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; Inflammation/drug therapy/metabolism ; },
abstract = {Retinal inflammation is a pivotal characteristic observed in various retinal degenerative disorders, notably age-related macular degeneration (AMD), primarily orchestrated by the activation of microglia. Targeting the inhibition of microglial activation has emerged as a therapeutic focal point. Quercetin (Qu), ubiquitously present in dietary sources and tea, has garnered attention for its anti-neuroinflammatory properties. However, the impact of Qu on retinal inflammation and the associated mechanistic pathways remains incompletely elucidated. In this study, retinal inflammation was induced in adult male C57BL/6 J mice through intraperitoneal administration of LPS. The results revealed that Qu pre-treatment induces a phenotypic shift in microglia from M1 phenotype to M2 phenotype. Furthermore, Qu attenuated retinal inflammation and stabilized the integrity of the blood-retina barrier (BRB). In vitro experiments revealed that Qu impedes microglial activation, proliferation, and migration, primarily via modulation the ERK/STAT3 signaling pathway. Notably, these actions of Qu significantly contributed to the preservation of photoreceptors. Consequently, Qu pre-treatment holds promise as an effective strategy for controlling retinal inflammation and preserving visual function.},
}
@article {pmid38410512,
year = {2024},
author = {Sándor, N and Schneider, AE and Matola, AT and Barbai, VH and Bencze, D and Hammad, HH and Papp, A and Kövesdi, D and Uzonyi, B and Józsi, M},
title = {The human factor H protein family - an update.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1135490},
pmid = {38410512},
issn = {1664-3224},
mesh = {Humans ; *Complement Factor H/metabolism ; *Complement System Proteins ; Complement Activation ; },
abstract = {Complement is an ancient and complex network of the immune system and, as such, it plays vital physiological roles, but it is also involved in numerous pathological processes. The proper regulation of the complement system is important to allow its sufficient and targeted activity without deleterious side-effects. Factor H is a major complement regulator, and together with its splice variant factor H-like protein 1 and the five human factor H-related (FHR) proteins, they have been linked to various diseases. The role of factor H in inhibiting complement activation is well studied, but the function of the FHRs is less characterized. Current evidence supports the main role of the FHRs as enhancers of complement activation and opsonization, i.e., counter-balancing the inhibitory effect of factor H. FHRs emerge as soluble pattern recognition molecules and positive regulators of the complement system. In addition, factor H and some of the FHR proteins were shown to modulate the activity of immune cells, a non-canonical function outside the complement cascade. Recent efforts have intensified to study factor H and the FHRs and develop new tools for the distinction, quantification and functional characterization of members of this protein family. Here, we provide an update and overview on the versatile roles of factor H family proteins, what we know about their biological functions in healthy conditions and in diseases.},
}
@article {pmid38409807,
year = {2024},
author = {Romano, MR and Sorrentino, T and Allegrini, D and Tripepi, D and Stradiotto, E and Raimondi, R},
title = {Small-Incision new generation implantable miniature telescope surgical technique and patient outcomes.},
journal = {European journal of ophthalmology},
volume = {34},
number = {3},
pages = {888-892},
doi = {10.1177/11206721241236515},
pmid = {38409807},
issn = {1724-6016},
mesh = {Humans ; *Visual Acuity/physiology ; *Telescopes ; Macular Degeneration/surgery ; Aged ; Miniaturization ; },
abstract = {BACKGROUND: Various ocular implants were suggested as a means of enhancing vision in patients with advanced age related macular degeneration. Recently, a new generation of implantable telescopes has been released. The purpose of this study is to report the surgical technique of implantation along with patient outcomes.<br><br>METHODS: This work focuses on the surgical technique. Crucial surgical steps are carefully reported along with discussion on main drawbacks and limitations.<br><br>RESULTS: This approach uses a preloaded delivery system with improved features and requires a smaller incision. First patient outcomes are also reported.<br><br>CONCLUSIONS: Surgical steps to implant this preloaded intraocular telescope are easier than previous versions, however this remains a complex procedure. Initial patient functional outcomes look promising.},
}
@article {pmid38408445,
year = {2024},
author = {Szeto, SKH and Tsang, CW and Mohamed, S and Lee, GKY and Lok, JKH and Hui, VWK and Tsang, KK and Chen, LJ and Brelen, M and Lai, TYY},
title = {Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {2},
pages = {118-132},
pmid = {38408445},
issn = {1423-0267},
mesh = {Humans ; Retrospective Studies ; *Retinal Hemorrhage/diagnosis/therapy/etiology ; Male ; Female ; *Vitrectomy/methods ; *Visual Acuity ; Aged ; *Endotamponade/methods ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Intravitreal Injections ; Angiogenesis Inhibitors/administration &amp; dosage ; Follow-Up Studies ; Treatment Outcome ; Wet Macular Degeneration/diagnosis/therapy/complications ; Fundus Oculi ; Fibrinolytic Agents/administration &amp; dosage ; Fluorocarbons/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; Middle Aged ; Sulfur Hexafluoride/administration &amp; dosage ; },
abstract = {INTRODUCTION: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery.<br><br>METHODS: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation.<br><br>RESULTS: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 &#x3bc;m vs. 780.2 &#x3bc;m, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p < 0.001). The mean postoperative VA at 6 months was 0.67 and 0.91 (p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 &#x3bc;m vs. 326.5 &#x3bc;m, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p < 0.001, odds ratio [OR] = 11.1) and displacement to arcade or beyond (52.5% vs. 17.5%, p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation.<br><br>CONCLUSION: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.},
}
@article {pmid38408187,
year = {2024},
author = {Liu, K and Zhang, X and Liu, R and Su, W and Song, Y and Tan, M},
title = {Preparation of Lutein Nanoparticles by Glycosylation of Saccharides and Casein for Protecting Retinal Pigment Epithelial Cells.},
journal = {Journal of agricultural and food chemistry},
volume = {72},
number = {12},
pages = {6347-6359},
doi = {10.1021/acs.jafc.3c09054},
pmid = {38408187},
issn = {1520-5118},
mesh = {Humans ; Aged ; Lutein ; Antioxidants/pharmacology ; Caseins ; Glycosylation ; Retinal Pigment Epithelium ; *Macular Degeneration/pathology ; Epithelial Cells ; *Nanoparticles ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of visual impairment in the aging population, lacks effective treatment options due to a limited understanding of its pathogenesis. Lutein, with its strong antioxidant properties and ability to mitigate AMD by absorbing ultraviolet (UV) rays, faces challenges related to its stability and bioavailability in functional foods. In this study, we aimed to develop delivery systems using protein-saccharide conjugates to enhance lutein delivery and protect adult retinal pigment epithelial (ARPE-19) cells against sodium iodate (NaIO3)-induced damage. Various saccharides, including mannose, galactose, lactose, maltose, dextran, and maltodextrin, were conjugated to casein via the Maillard reaction for lutein delivery. The resulting lutein-loaded nanoparticles exhibited small size and spherical characteristics and demonstrated improved thermal stability and antioxidant capacity compared to free lutein. Notably, these nanoparticles were found to be nontoxic, as evidenced by reduced levels of cellular reactive oxygen species production (167.50 ± 3.81, 119.57 ± 3.45, 195.15 ± 1.41, 183.96 ± 3.11, 254.21 ± 3.97, 283.56 ± 7.27%) and inhibition of the mitochondrial membrane potential decrease (58.60 ± 0.29, 65.05 ± 2.91, 38.88 ± 1.81, 42.95 ± 1.39, 23.52 ± 1.04, 25.24 ± 0.08%) caused by NaIO3, providing protection against cellular damage and death. Collectively, our findings suggest that lutein-loaded nanoparticles synthesized via the Maillard reaction hold promise for enhanced solubility, oral bioavailability, and biological efficacy in the treatment of AMD.},
}
@article {pmid38408093,
year = {2024},
author = {Sorenson, CM and Gurel, Z and Song, YS and Peterson, KD and Blodi, BA and Sheibani, N},
title = {Thrombospondin-1, BIM and CFH polymorphisms and response to anti-VEGF treatment in neovascular age- related macular degeneration patients.},
journal = {PloS one},
volume = {19},
number = {2},
pages = {e0297135},
pmid = {38408093},
issn = {1932-6203},
support = {P30 CA014520/CA/NCI NIH HHS/United States ; P30 EY016665/EY/NEI NIH HHS/United States ; R01 EY030076/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Angiogenesis Inhibitors ; Complement Factor H/genetics ; Vascular Endothelial Growth Factor A/genetics ; Visual Acuity ; *Wet Macular Degeneration ; Polymorphism, Single Nucleotide ; Thrombospondins/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a vision threatening disease in older adults. Anti-VEGF treatment is effective for the majority of neovascular AMD (nAMD) patients, although approximately 30% of nAMD patients have an incomplete response for unknown reasons. Here we assessed the contribution of single nucleotide polymorphisms (SNPs) in key angioinflammatory regulatory genes in nAMD patients with an incomplete response compared to those responsive to anti-VEGF treatment. A total of 25 responsive and 30 nAMD patients with an incomplete response to anti-vascular endothelial growth factor (anti-VEGF) treatment were examined for known SNPs that impact the structure and function of thromobospondin-1 (TSP1), Bcl-2-interacting mediator of cell death (BIM) and complement factor H (CFH). Plasma levels of C-C motif chemokine ligand 2 (CCL2/MCP1), TSP1 and VEGF were assessed by ELISA. Patients responsive to anti-VEGF treatment showed a significant increase in the TSP1 rs2228262 AA allele and a trend for the BIM (rs724710) CT allele. Consistent with previous reports, 42% of the patients responsive to anti-VEGF expressed the CC allele for CFH rs1061170. Although the CFH TT allele had similarly low prevalence in both groups, the TC allele tended to be more prevalent in patients with an incomplete response. Patients with an incomplete response also had increased plasma CCL2/MCP1 levels, consistent with the role increased inflammation has in the pathogenesis of nAMD. Our studies point to new tools to assess the potential responsiveness of nAMD patients to anti-VEGF treatment and suggest the potential use of anti-CCL2 for treatment of nAMD patients with an incomplete response to anti-VEGF.},
}
@article {pmid38407857,
year = {2024},
author = {Mordechaev, E and Jo, JJ and Mordechaev, S and Govindaiah, A and Fei, Y and Tai, K and Tong, Y and Bhuiyan, A and Weinberger, J and Deobhakta, A and Dhamoon, M and Rosen, RB and Lema, GMC and Smith, RT},
title = {Internal Carotid Artery Stenosis and Ipsilateral Subretinal Drusenoid Deposits.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {2},
pages = {37},
pmid = {38407857},
issn = {1552-5783},
mesh = {Male ; Humans ; Female ; *Carotid Stenosis/diagnosis/diagnostic imaging ; Constriction, Pathologic ; Cross-Sectional Studies ; Choroid ; *Ischemic Stroke ; Dapsone/*analogs &amp; derivatives ; },
abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are strongly associated with vasculopathies such as myocardial infarction and ischemic stroke. This study evaluates ischemic stroke subjects for SDDs to determine whether ocular hypoperfusion from internal carotid artery (ICA) stenosis is associated with ipsilateral SDDs.<br><br>METHODS: A cross-sectional study at Mount Sinai Hospital recruited 39 subjects with ischemic stroke (aged 52-90; 18 women, 21 men); 28 completed all study procedures. Computed tomography (CT) of the head and neck evaluated 54/56 ICAs for stenosis criteria: none (n = 33), mild (n = 12), moderate (n = 3), severe (n = 3), and complete (n = 3). Spectral-domain optical coherence tomography (SD-OCT) scans were read to consensus by two masked graders for soft drusen, SDDs and choroidal thickness (CTh; choroidal thinning = CTh < 250&#xa0;&#xb5;m). Univariate testing was done with Fisher's exact test. Multivariate logistic regression models tested age, gender, and ICA stenosis as covariates.<br><br>RESULTS: Moderate or more ICA stenosis (&#x2265;50%-69%) was significantly associated with ipsilateral choroidal thinning (P = 0.021) and ipsilateral SDDs (P = 0.005); the latter were present distal to six of nine stenosed ICAs versus five of 33 normal ICAs. Mild ICA stenosis (&#x2265;1%-49%) was not significantly associated with ipsilateral SDDs. Multivariate regression found that older age (P = 0.015) and moderate or more ICA stenosis (P = 0.011) remained significant independent risks for ipsilateral SDDs.<br><br>CONCLUSIONS: At least moderate ICA stenosis (&#x2265;50%-69%) is strongly associated with ipsilateral SDDs and choroidal thinning, supporting downstream ophthalmic artery and choroidal hypoperfusion from ICA stenosis as the mechanism for SDD formation. SDDs may thus serve as sensitive biomarkers for ischemic stroke and other vascular diseases.},
}
@article {pmid38406826,
year = {2024},
author = {Huang, H and Zeng, J and Yu, X and Du, H and Wen, C and Mao, Y and Tang, H and Kuang, X and Liu, W and Yu, H and Liu, H and Li, B and Long, C and Yan, J and Shen, H},
title = {Establishing chronic models of age-related macular degeneration via long-term iron ion overload.},
journal = {American journal of physiology. Cell physiology},
volume = {326},
number = {5},
pages = {C1367-C1383},
doi = {10.1152/ajpcell.00532.2023},
pmid = {38406826},
issn = {1522-1563},
support = {81670874//MOST | National Natural Science Foundation of China (NSFC)/ ; 81670885//MOST | National Natural Science Foundation of China (NSFC)/ ; 2020A1515010144//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; 2021A1515010513//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; 2022A1515012442//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; N/A//Fundamental Research Funds of the State Key Laboratory of Ophthalmology/ ; N/A//Open Research Funds of the State Key Laboratory of Ophthalmology/ ; },
mesh = {Animals ; Humans ; *Macular Degeneration/metabolism/pathology/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Disease Models, Animal ; Mice ; *Iron/metabolism ; Mice, Inbred C57BL ; Apoptosis ; Oxidative Stress ; Cell Line ; Cellular Senescence ; Iron Overload/metabolism/pathology ; Cell Proliferation ; Retina/metabolism/pathology ; Mitochondria/metabolism/pathology ; },
abstract = {Age-related macular degeneration (AMD) is characterized by the degenerative senescence in the retinal pigment epithelium (RPE) and photoreceptors, which is accompanied by the accumulation of iron ions in the aging retina. However, current models of acute oxidative stress are still insufficient to simulate the gradual progression of AMD. To address this, we established chronic injury models by exposing the aRPE-19 cells, 661W cells, and mouse retina to iron ion overload over time. Investigations at the levels of cell biology and molecular biology were performed. It was demonstrated that long-term treatment of excessive iron ions induced senescence-like morphological changes, decreased cell proliferation, and impaired mitochondrial function, contributing to apoptosis. Activation of the mitogen-activated protein kinase (MAPK) pathway and the downstream molecules were confirmed both in the aRPE-19 and 661W cells. Furthermore, iron ion overload resulted in dry AMD-like lesions and decreased visual function in the mouse retina. These findings suggest that chronic exposure to overloading iron ions plays a significant role in the pathogenesis of retinopathy and provide a potential model for future studies on AMD.NEW &amp; NOTEWORTHY To explore the possibility of constructing reliable research carriers on age-related macular degeneration (AMD), iron ion overload was applied to establish models in vitro and in vivo. Subsequent investigations into cellular physiology and molecular biology confirmed the presence of senescence in these models. Through this study, we hope to provide a better option of feasible methods for future researches into AMD.},
}
@article {pmid38406066,
year = {2024},
author = {Correia Barbosa, R and Teixeira, C},
title = {Spontaneous Massive Retinal Pigment Epithelium Tear: A Case Report of a Dramatic Complication of Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {16},
number = {1},
pages = {e52980},
pmid = {38406066},
issn = {2168-8184},
abstract = {Retinal pigment epithelium (RPE) tears occur when the RPE acutely breaks and retracts, leaving the underlying Bruch's membrane and choroid exposed. They usually happen in areas of previous pigment epithelial detachments and are generally associated with age-related macular degeneration (AMD). The purpose of this report is to describe a case of a spontaneous massive central RPE tear in a patient with untreated AMD. A 67-year-old female patient presented with complaints of sudden decreased vision in her right eye. Her best-corrected visual acuity was 2/20, and fundoscopy revealed a massive central retinal hemorrhage with intraretinal, subretinal, and sub-RPE blood. The patient started anti-vascular endothelial growth factor (VEGF) treatment, and after the blood was reabsorbed, a very large central tear of the RPE involving the central macula was evident, with a layer of detached retina folded on itself. She received continuous anti-VEGF therapy, and the final measurement of her visual acuity was 2/200, despite the complete reabsorption of the hemorrhage. RPE tears may occur spontaneously as part of the natural history of AMD or be triggered by the initiation of anti-VEGF treatment in the presence of large pigment epithelium detachments. There are currently no strategies to prevent their spontaneous development, and they constitute a dramatic complication of AMD. The prognosis is dependent on the size and location of the lesion, and the visual loss is irreversible.},
}
@article {pmid38405807,
year = {2024},
author = {Mishra, Z and Wang, Z and Xu, E and Xu, S and Majid, I and Sadda, SR and Hu, ZJ},
title = {Recurrent and Concurrent Prediction of Longitudinal Progression of Stargardt Atrophy and Geographic Atrophy.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {38405807},
support = {R21 EY029839/EY/NEI NIH HHS/United States ; },
abstract = {Stargardt disease and age-related macular degeneration are the leading causes of blindness in the juvenile and geriatric populations, respectively. The formation of atrophic regions of the macula is a hallmark of the end-stages of both diseases. The progression of these diseases is tracked using various imaging modalities, two of the most common being fundus autofluorescence (FAF) imaging and spectral-domain optical coherence tomography (SD-OCT). This study seeks to investigate the use of longitudinal FAF and SD-OCT imaging (month 0, month 6, month 12, and month 18) data for the predictive modelling of future atrophy in Stargardt and geographic atrophy. To achieve such an objective, we develop a set of novel deep convolutional neural networks enhanced with recurrent network units for longitudinal prediction and concurrent learning of ensemble network units (termed ReConNet) which take advantage of improved retinal layer features beyond the mean intensity features. Using FAF images, the neural network presented in this paper achieved mean (± standard deviation, SD) and median Dice coefficients of 0.895 (± 0.086) and 0.922 for Stargardt atrophy, and 0.864 (± 0.113) and 0.893 for geographic atrophy. Using SD-OCT images for Stargardt atrophy, the neural network achieved mean and median Dice coefficients of 0.882 (± 0.101) and 0.906, respectively. When predicting only the interval growth of the atrophic lesions with FAF images, mean (± SD) and median Dice coefficients of 0.557 (± 0.094) and 0.559 were achieved for Stargardt atrophy, and 0.612 (± 0.089) and 0.601 for geographic atrophy. The prediction performance in OCT images is comparably good to that using FAF which opens a new, more efficient, and practical door in the assessment of atrophy progression for clinical trials and retina clinics, beyond widely used FAF. These results are highly encouraging for a high-performance interval growth prediction when more frequent or longer-term longitudinal data are available in our clinics. This is a pressing task for our next step in ongoing research.},
}
@article {pmid38405106,
year = {2024},
author = {Thomsen, AK and Krogh Nielsen, M and Liisborg, C and Sørensen, TL},
title = {Interleukin-8 Promoter Polymorphism -251 A/T and Treatment Response in Neovascular Age-related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {537-543},
pmid = {38405106},
issn = {1177-5467},
abstract = {PURPOSE: Interleukin-8 (IL-8) is a potent pro-angiogenic and pro-inflammatory chemokine, suggested to hold a role in neovascular age-related macular degeneration (nAMD). Our aim is to study the association of the single-nucleotide polymorphism -251 A/T (rs4073) in the IL-8 promoter region with the treatment response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in nAMD.<br><br>PATIENTS AND METHODS: This is a prospective study of treatment-na&#xef;ve patients with nAMD. Treatment response after a loading dose of three intravitreal anti-VEGF injections was defined as functional response based on change in visual acuity, and morphological response based on change in central retinal thickness (CRT) and intraretinal fluid on optical coherence tomography. Morphological response was categorized in good, partial, and poor responders. Blood DNA was analyzed for -251 A/T genotype.<br><br>RESULTS: The IL-8 promoter polymorphism -251 A/T was not significantly associated to functional treatment response (P=0.09). No significant association was found between genotype and morphological treatment response (P=0.799). Older age was significantly associated to good morphological responders compared to partial and poor responders (P=0.014).<br><br>CONCLUSION: The IL-8 polymorphism -251 A/T is not associated to morphological nor functional treatment response to intravitreal anti-VEGF injections in patients with nAMD.},
}
@article {pmid38405104,
year = {2024},
author = {Tanaka, A and Hata, M and Tsuchikawa, M and Ueda-Arakawa, NU and Tamura, H and Miyata, M and Takahashi, A and Kido, A and Muraoka, Y and Miyake, M and Ooto, S and Tsujikawa, A},
title = {Short-Term Outcomes of 3 Monthly intravitreal Faricimab On Different Subtypes of Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {507-516},
pmid = {38405104},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the efficacy and safety of faricimab injections for treatment-naïve neovascular age-related macular degeneration (nvAMD) patients, including subtypes and pachychoroid phenotypes, and identify predictive factors for visual outcomes.<br><br>METHODS: nvAMD patients were prospectively recruited, receiving three monthly faricimab (6 mg) injections. Best-corrected visual acuity (BCVA) two months after the last injection (month 4) was compared between subtypes, and between pachychoroid neovasculopathy (PNV) and non-PNV eyes. Regression analysis determined factors influencing month 4 BCVA.<br><br>RESULTS: The study involved 23 patients (12 typical AMD [tAMD], 10 polypoidal choroidal vasculopathy [PCV], 1 retinal angiomatous proliferation [RAP]). Eleven exhibited PNV phenotype. Significant BCVA (P = 4.9 &#xd7; 10[-4]) and central retinal thickness (CRT) (P = 1.3 &#xd7; 10[-5]) improvements were observed post-faricimab treatment. The therapy demonstrated favourable results for both tAMD and PCV eyes, and non-PNV and PNV eyes. Faricimab achieved dry macula in 77.3% of eyes, with subretinal fluid resolution in most cases, although intraretinal fluid (IRF) often persisted. Multivariable analysis identified external limiting membrane (ELM) presence and IRF as BCVA contributors at month 4.<br><br>CONCLUSION: Faricimab demonstrated significant effectiveness and safety in treatment-na&#xef;ve nvAMD patients, particularly for PCV and PNV eyes. ELM presence and IRF is predictive of visual outcomes.},
}
@article {pmid38404341,
year = {2024},
author = {Liu, R and Wang, X and Hoshi, S and Zhang, Y},
title = {Substrip-based registration and automatic montaging of adaptive optics retinal images.},
journal = {Biomedical optics express},
volume = {15},
number = {2},
pages = {1311-1330},
pmid = {38404341},
issn = {2156-7085},
support = {R01 EY024378/EY/NEI NIH HHS/United States ; R01 EY034218/EY/NEI NIH HHS/United States ; },
abstract = {Precise registration and montage are critical for high-resolution adaptive optics retinal image analysis but are challenged by rapid eye movement. We present a substrip-based method to improve image registration and facilitate the automatic montaging of adaptive optics scanning laser ophthalmoscopy (AOSLO). The program first batches the consecutive images into groups based on a translation threshold and selects an image with minimal distortion within each group as the reference. Within each group, the software divides each image into multiple strips and calculates the Normalized Cross-Correlation with the reference frame using two substrips at both ends of the whole strip to estimate the strip translation, producing a registered image. Then, the software aligns the registered images of all groups also using a substrip based registration, thereby generating a montage with cell-for-cell precision in the overlapping areas of adjacent frames. The algorithm was evaluated with AOSLO images acquired in human subjects with normal macular health and patients with age-related macular degeneration (AMD). Images with a motion amplitude of up to 448 pixels in the fast scanner direction over a frame of 512 × 512 pixels can be precisely registered. Automatic montage spanning up to 22.6 degrees on the retina was achieved on a cell-to-cell precision with a low misplacement rate of 0.07% (11/16,501 frames) in normal eyes and 0.51% (149/29,051 frames) in eyes with AMD. Substrip based registration significantly improved AOSLO registration accuracy.},
}
@article {pmid38404340,
year = {2024},
author = {Li, M and Shen, Y and Wu, R and Huang, S and Zheng, F and Chen, S and Wang, R and Dong, W and Zhong, J and Ni, G and Liu, Y},
title = {High-accuracy 3D segmentation of wet age-related macular degeneration via multi-scale and cross-channel feature extraction and channel attention.},
journal = {Biomedical optics express},
volume = {15},
number = {2},
pages = {1115-1131},
pmid = {38404340},
issn = {2156-7085},
abstract = {Wet age-related macular degeneration (AMD) is the leading cause of visual impairment and vision loss in the elderly, and optical coherence tomography (OCT) enables revolving biotissue three-dimensional micro-structure widely used to diagnose and monitor wet AMD lesions. Many wet AMD segmentation methods based on deep learning have achieved good results, but these segmentation results are two-dimensional, and cannot take full advantage of OCT's three-dimensional (3D) imaging characteristics. Here we propose a novel deep-learning network characterizing multi-scale and cross-channel feature extraction and channel attention to obtain high-accuracy 3D segmentation results of wet AMD lesions and show the 3D specific morphology, a task unattainable with traditional two-dimensional segmentation. This probably helps to understand the ophthalmologic disease and provides great convenience for the clinical diagnosis and treatment of wet AMD.},
}
@article {pmid38404299,
year = {2024},
author = {Kapahi, C and Silva, AE and Cory, DG and Kulmaganbetov, M and Mungalsingh, MA and Pushin, DA and Singh, T and Thompson, B and Sarenac, D},
title = {Measuring the visual angle of polarization-related entoptic phenomena using structured light.},
journal = {Biomedical optics express},
volume = {15},
number = {2},
pages = {1278-1287},
pmid = {38404299},
issn = {2156-7085},
abstract = {The ability to perceive polarization-related entoptic phenomena arises from the dichroism of macular pigments held in Henle's fiber layer of the retina and can be inhibited by retinal diseases, such as age-related macular degeneration, which alters the structure of the macula. Structured light tools enable the direct probing of macular pigment density and retinal structure through the perception of polarization-dependent entoptic patterns. Here, we directly measure the visual angle of an entoptic pattern created through the illumination of the retina with a structured state of light and a perception task that is insensitive to corneal birefringence. The central region of the structured light stimuli was obstructed, with the size of the obstruction varying according to a psychophysical staircase. Two stimuli, one producing 11 azimuthal fringes and the other three azimuthal fringes, were presented to 24 healthy participants. The pattern with 11 azimuthal fringes produced an average visual angle threshold of 10° ± 1° and a 95% confidence interval (C.I.) of [6°, 14°]. For the pattern with three azimuthal fringes, a threshold extent of 3.6° ± 0.3° C.I. = [1.3°, 5.8°] was measured, a value similar to the published extent of Haidinger's brush (4°). The increase in apparent size and clarity of entoptic phenomena produced by the presented structured light stimuli offers the potential to detect the early signs of macular disease over perception tasks using uniform polarization stimuli.},
}
@article {pmid38403816,
year = {2024},
author = {Zech, TJ and Wolf, A and Hector, M and Bischoff-Kont, I and Krishnathas, GM and Kuntschar, S and Schmid, T and Bracher, F and Langmann, T and Fürst, R},
title = {2-Desaza-annomontine (C81) impedes angiogenesis through reduced VEGFR2 expression derived from inhibition of CDC2-like kinases.},
journal = {Angiogenesis},
volume = {27},
number = {2},
pages = {245-272},
pmid = {38403816},
issn = {1573-7209},
support = {321115009//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Animals ; Humans ; Mice ; Angiogenesis ; Angiogenesis Inhibitors/pharmacology ; *beta Catenin/metabolism ; *Carbolines ; Endothelial Cells/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Inflammation ; Neovascularization, Pathologic/drug therapy ; *Pyrimidines ; *Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Wnt Signaling Pathway ; },
abstract = {Angiogenesis is a crucial process in the progression of various pathologies, like solid tumors, wet age-related macular degeneration, and chronic inflammation. Current anti-angiogenic treatments still have major drawbacks like limited efficacy in diseases that also rely on inflammation. Therefore, new anti-angiogenic approaches are sorely needed, and simultaneous inhibition of angiogenesis and inflammation is desirable. Here, we show that 2-desaza-annomontine (C81), a derivative of the plant alkaloid annomontine previously shown to inhibit endothelial inflammation, impedes angiogenesis by inhibiting CDC2-like kinases (CLKs) and WNT/β-catenin signaling. C81 reduced choroidal neovascularization in a laser-induced murine in vivo model, inhibited sprouting from vascular endothelial growth factor A (VEGF-A)-activated murine aortic rings ex vivo, and reduced angiogenesis-related activities of endothelial cells in multiple functional assays. This was largely phenocopied by CLK inhibitors and knockdowns, but not by inhibitors of the other known targets of C81. Mechanistically, CLK inhibition reduced VEGF receptor 2 (VEGFR2) mRNA and protein expression as well as downstream signaling. This was partly caused by a reduction of WNT/β-catenin pathway activity, as activating the pathway induced, while β-catenin knockdown impeded VEGFR2 expression. Surprisingly, alternative splicing of VEGFR2 was not detected. In summary, C81 and other CLK inhibitors could be promising compounds in the treatment of diseases that depend on angiogenesis and inflammation due to their impairment of both processes.},
}
@article {pmid38403242,
year = {2024},
author = {Ehlers, JP and Lunasco, LM and Yordi, S and Cetin, H and Le, TK and Sarici, K and Kaiser, PK and Khanani, AM and Talcott, KE and Hu, J and Meng, X and Srivastava, SK},
title = {Compartmental Exudative Dynamics in Neovascular Age-Related Macular Degeneration: Volumetric Outcomes and Impact of Volatility in a Phase III Clinical Trial.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {8},
pages = {765-777},
doi = {10.1016/j.oret.2024.02.010},
pmid = {38403242},
issn = {2468-6530},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Antibodies, Monoclonal, Humanized/administration &amp; dosage/therapeutic use ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors/therapeutic use ; Recombinant Fusion Proteins/administration &amp; dosage ; Retinal Pigment Epithelium/pathology ; Subretinal Fluid ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; },
abstract = {PURPOSE: To examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy and the relationship of these features with visual acuity.<br><br>DESIGN: Post hoc analysis of the phase III, randomized, HAWK nAMD clinical trial.<br><br>PARTICIPANTS: Participants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial.<br><br>METHODS: Spectral-domain OCT scans collected at 4-week intervals were analyzed using an automated machine learning-enhanced segmentation and feature-extraction platform with manual verification. Quantitative volumetric measures of retinal and exudative features were exported at multiple timepoints over 48 weeks. Volatility of exudative features was calculated as the standard deviation of each feature value during the maintenance phase (week 12-48) of treatment. These features were examined for their associations with anatomic and functional outcomes.<br><br>MAIN OUTCOME MEASURES: Longitudinal intraretinal fluid (IRF) and subretinal fluid (SRF) volume, subretinal hyperreflective material (SHRM) volume, ellipsoid zone (EZ) integrity (EZ-retinal pigment epithelium [RPE] volume/thickness), and correlation with best-corrected visual acuity (BCVA).<br><br>RESULTS: Intraretinal fluid, SRF, and SHRM demonstrated significant volumetric reduction from baseline with anti-VEGF therapy (P < 0.001 at each timepoint). Ellipsoid zone integrity measures demonstrated significant improvement from baseline (P < 0.001 at each timepoint). Both EZ integrity and SHRM measures correlated significantly with BCVA at all timepoints (EZ-RPE volume: 0.38 &#x2264; r &#x2264; 0.47; EZ-RPE central subfield thickness: 0.22 &#x2264; r &#x2264; 0.41; SHRM volume:&#xa0;-0.33 &#x2264; r &#x2264;&#xa0;-0.44). After treatment initiation, correlations of IRF and SRF volume with BCVA were weak or nonsignificant. Eyes with lower volatility of IRF, SRF, and SHRM volumes during the maintenance phase showed greater improvements in EZ integrity (all P < 0.01) and greater gains in BCVA (all P < 0.01) at week 48 compared with eyes with higher volatility in those exudative parameters.<br><br>CONCLUSIONS: Quantitative measures of SHRM volume and EZ integrity correlated more strongly with BCVA than retinal fluid volumes during treatment. High volatility of exudative parameters, including SRF, during the maintenance phase of treatment was associated with loss of EZ integrity and BCVA.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38399372,
year = {2024},
author = {Almuiña-Varela, P and García-Quintanilla, L and Rodríguez-Cid, MJ and Gil-Martínez, M and Abraldes, MJ and Gómez-Ulla, F and Estany-Gestal, A and Alcántara-Espinosa, JM and Fernández-Rodríguez, M and Fernández-Ferreiro, A},
title = {Relationships between Patient-Reported Outcome Measures and Clinical Measures in Naïve Neovascular Age-Related Macular Degeneration Patients Treated with Intravitreal Ranibizumab.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {2},
pages = {},
pmid = {38399372},
issn = {1424-8247},
support = {PI17/00940//Instituto de Salud Carlos III/ ; IN607D 2021/001//Xunta de Galicia/ ; },
abstract = {Our objective was to evaluate changes in patient-reported outcome measures using the NEI-VFQ 25 questionnaire during a treat and extend regimen in naive neovascular Age-Related Macular Degeneration patients, and its correlation with anatomical and functional data. We conducted a prospective observational study. Patients underwent a treat and extend regimen with intravitreal ranibizumab for neovascular Age-Related Macular Degeneration. Initial response was evaluated at 4th month, and subsequently in every follow-up visit. If a clinical response was achieved, the injection interval was extended in two-week increments, up to a maximum of 12 weeks. Quality of life was assessed using the NEI-VFQ 25 questionnaire at baseline, 4th months, and 12th months. Patients were categorized as good or poor responders based on Best corrected visual acuity, central foveal thickness, intraretinal fluid, or subretinal fluid. Treatment with ranibizumab led to a significant improvement in quality of life, with a mean increase in NEI-VFQ 25 score of 4.27 points in the 12th month. No significant differences in improvement were observed between good and poor responders. Quality of life scores in neovascular Age-Related Macular Degeneration patients improved with intravitreal treatment regardless of the clinical response. The early response following the loading phase could indicate better quality of life after one year of treatment, with Best corrected visual acuity being the clinical parameter with the greatest influence on quality of life.},
}
@article {pmid38398702,
year = {2024},
author = {Ng, B and Kolli, H and Ajith Kumar, N and Azzopardi, M and Logeswaran, A and Buensalido, J and Mushtaq, B and Chavan, R and Chong, YJ},
title = {Real-World Data on Faricimab Switching in Treatment-Refractory Neovascular Age-Related Macular Degeneration.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
pmid = {38398702},
issn = {2075-1729},
abstract = {Faricimab is a newly approved bispecific antibody for neovascular age-related macular degeneration (nAMD). Our study aims to evaluate clinical outcomes of faricimab switching in patients with treatment-refractory nAMD; determine parameters that predict these outcomes; and obtain patient subjective experience on this new injection. This is a retrospective case review with clinical and imaging data from a tertiary referral unit (Birmingham and Midland Eye Centre, UK), involving patients who were switched to faricimab between 1 January and 1 December 2023. In all, 63 eyes (54 patients) with a mean age of 79.2 ± 7.8 and mean of 41.5 ± 22.4 previous anti-VEGF injections were analysed. With a mean of 4.81 ± 1.16 faricimab injections over 6.98 ± 1.75 months, post-treatment visual acuity was logMAR 0.49 ± 0.36 and central macular thickness (CMT) was 320.3 ± 97.9 µm. After first dose, 39.1% achieved complete dryness and 89.1% had anatomical improvement. Presence of subretinal fluid was a predictor of better functional outcomes (p = 0.001, β = -0.182), while initial CMT predicted better anatomical outcomes (p = 0.001, β = 0.688). Compared to their experiences of previous anti-VEGF injections, 89% of patients reported no more discomfort and 87.0% experienced no more floaters, photopsia, or bubbles post-injection. Faricimab switching has anatomical efficacy but limited functional improvement in treatment-refractory AMD. Patient experiences of faricimab compared to previous injections were overall positive.},
}
@article {pmid38398387,
year = {2024},
author = {Schranz, M and Sacu, S and Reiter, GS and Baratsits, M and Desissaire, S and Pircher, M and Mylonas, G and Hitzenberger, C and Schmidt-Erfurth, U and Roberts, PK},
title = {Structure-Function Correlation of Retinal Fibrosis in Eyes with Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {4},
pages = {},
pmid = {38398387},
issn = {2077-0383},
support = {KLI 749/FWF_/Austrian Science Fund FWF/Austria ; KLI 749-B//FWF Austrian Science Fund/ ; },
abstract = {Purpose: To assess retinal function in areas of presumed fibrosis due to neovascular age-related macular degeneration (nAMD), using multimodal imaging and structure-function correlation. Design: Cross-sectional observational study. Methods: 30 eyes of 30 consecutive patients with nAMD with a minimum history of one year of anti-vascular endothelial growth factor therapy were included. Each patient underwent microperimetry (MP), color fundus photography (CFP), standard spectral-domain-based OCT (SD-OCT), and polarization sensitive-OCT (PS-OCT) imaging. PS-OCT technology can depict retinal fibrosis based on its birefringence. CFP, SD-OCT, and PS-OCT were evaluated independently for the presence of fibrosis at the corresponding MP stimuli locations. MP results and morphologic findings in CFP, SD-OCT, and PS-OCT were co-registered and analyzed using mixed linear models. Results: In total, 1350 MP locations were evaluated to assess the functional impact of fibrosis according to a standardized protocol. The estimated means of retinal areas with signs of fibrosis were 12.60 db (95% confidence interval: 10.44-14.76) in CFP, 11.60 db (95% COI: 8.84-14.36) in OCT, and 11.02 db (95% COI 8.10-13.94) in PS-OCT. Areas evaluated as subretinal fibrosis in three (7.2 db) or two (10.1 db) modalities were significantly correlated with a lower retinal sensitivity than a subretinal fibrosis observed in only one (15.3 db) or none (23.3 db) modality (p < 0.001). Conclusions: CFP, SD-OCT and PS-OCT are all suited to detect areas of reduced retinal sensitivity related to fibrosis, however, a multimodal imaging approach provides higher accuracy in the identification of areas with low sensitivity in MP (i.e., impaired retinal function), and thereby improves the detection rate of subretinal fibrosis in nAMD.},
}
@article {pmid38397993,
year = {2024},
author = {Kozhevnikova, O},
title = {Advanced Research in Age-Related Macular Degeneration: Special Issue.},
journal = {Biomedicines},
volume = {12},
number = {2},
pages = {},
pmid = {38397993},
issn = {2227-9059},
support = {FWNR-2022-0016//the State Budget Project/ ; },
abstract = {Age-related macular degeneration (AMD) is an eye disease that is the leading cause of irreversible vision loss in people over 55 years of age [...].},
}
@article {pmid38397064,
year = {2024},
author = {Blasiak, J and Pawlowska, E and Ciupińska, J and Derwich, M and Szczepanska, J and Kaarniranta, K},
title = {A New Generation of Gene Therapies as the Future of Wet AMD Treatment.},
journal = {International journal of molecular sciences},
volume = {25},
number = {4},
pages = {},
pmid = {38397064},
issn = {1422-0067},
mesh = {Humans ; *Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/therapy/drug therapy ; Genetic Therapy ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms, dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the concept of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the progress to the clinic of "one and done" therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.},
}
@article {pmid38396439,
year = {2024},
author = {Kusenda, P and Caprnda, M and Gabrielova, Z and Kukova, N and Pavlovic, S and Stefanickova, J},
title = {Understanding Loss to Follow-Up in AMD Patients Receiving VEGF Inhibitor Therapy: Associated Factors and Underlying Reasons.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {38396439},
issn = {2075-4418},
abstract = {BACKGROUND: In patients with wet age-related macular degeneration (AMD), loss to follow-up (LTFU) leads to unplanned interruptions in therapy and the risk of visual loss.<br><br>METHODS: This retrospective and prospective case-control cohort study compared AMD patients with (LTFU YES) and without (LTFU NO) LTFU during anti-VEGF treatment over 12 years. LTFU was defined as missing any treatment or monitoring visits, or not scheduling follow-ups for six months.<br><br>RESULTS: Significant differences between LTFU NO (n = 298) and LTFU YES (n = 174) groups were age, treatment phase, baseline and final best-corrected visual acuity (BCVA), type of anti-VEGF drug, treatment switch, commuting distance, and escort during commuting. A multivariate logistic regression analysis identified the need for an escort during the commuting and treatment phase as the only significant difference. The four most common reasons for LTFU were general health worsening (21.8%), patient-missed appointments (16.7%), COVID-19-related issues (14.9%), and treatment dissatisfaction (8.6%).<br><br>CONCLUSIONS: The factors associated with increased LTFU rates were older age, inactive treatment phase, lower baseline and final BCVA, bevacizumab treatment, monotherapy, longer travelling distance, and commuting with an escort. According to the multivariate logistic regression analysis, only the escort during the commuting and treatment phases was significant. These findings could direct research to explore social support in treatment adherence and highlight the importance of treatment phases in practice.},
}
@article {pmid38396072,
year = {2024},
author = {Andrews, PW},
title = {The origins of human pluripotent stem cells: the road from a cancer to regenerative medicine.},
journal = {In vitro cellular &amp; developmental biology. Animal},
volume = {60},
number = {5},
pages = {514-520},
pmid = {38396072},
issn = {1543-706X},
support = {MR/V002163/1/MRC_/Medical Research Council/United Kingdom ; MR/L012537/1/MRC_/Medical Research Council/United Kingdom ; H2020-FETPROACT-2018-01//H2020 European Institute of Innovation and Technology/ ; },
mesh = {Humans ; *Regenerative Medicine ; *Pluripotent Stem Cells/cytology ; Animals ; Neoplasms/pathology/therapy ; Mice ; },
abstract = {The notion of using pluripotent stem cells (PSCs) as a source of differentiated cell types for replacement of disease or damaged tissues in regenerative medicine is now an active area of research, with approaches to treating eye diseases such as age-related macular degeneration or Parkinson's disease now on the horizon. But the foundations for this research lie in a quite different area of science, namely the role of genetics of cancer. In this review, we trace the evolution of ideas starting with the discovery that strain 129 mice are particularly subject to develop germ cell tumors, through the identification of embryonal carcinoma (EC) cells as the stem cells of the teratocarcinoma manifestation of these tumors, to the recognition of their relationship to pluripotent cells of the early embryo, and eventually their role in the derivation of embryonic stem cells, first from mouse embryos and then from primates including humans. This is a story that illustrates how science commonly develops through the interests and insights of individual investigators, often with unexpected and unintended outcomes.},
}
@article {pmid38394676,
year = {2024},
author = {Shen, E and Wang, Z and Lin, T and Meng, Q and Zhu, W and Shi, F and Chen, X and Chen, H and Xiang, D},
title = {DRFNet: a deep radiomic fusion network for nAMD/PCV differentiation in OCT images.},
journal = {Physics in medicine and biology},
volume = {69},
number = {7},
pages = {},
doi = {10.1088/1361-6560/ad2ca0},
pmid = {38394676},
issn = {1361-6560},
mesh = {Humans ; *Polypoidal Choroidal Vasculopathy ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Radiomics ; Fluorescein Angiography/methods ; Retrospective Studies ; },
abstract = {Objective.Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) present many similar clinical features. However, there are significant differences in the progression of nAMD and PCV. and it is crucial to make accurate diagnosis for treatment. In this paper, we propose a structure-radiomic fusion network (DRFNet) to differentiate PCV and nAMD in optical coherence tomography (OCT) images.Approach.The subnetwork (RIMNet) is designed to automatically segment the lesion of nAMD and PCV. Another subnetwork (StrEncoder) is designed to extract deep structural features of the segmented lesion. The subnetwork (RadEncoder) is designed to extract radiomic features from the segmented lesions based on radiomics. 305 eyes (155 with nAMD and 150 with PCV) are included and manually annotated CNV region in this study. The proposed method was trained and evaluated by 4-fold cross validation using the collected data and was compared with the advanced differentiation methods.Main results.The proposed method achieved high classification performace of nAMD/PCV differentiation in OCT images, which was an improvement of 4.68 compared with other best method.Significance. The presented structure-radiomic fusion network (DRFNet) has great performance of diagnosing nAMD and PCV and high clinical value by using OCT instead of indocyanine green angiography.},
}
@article {pmid38394392,
year = {2024},
author = {Klymenko, V and González Martínez, OG and Zarbin, M},
title = {Recent Progress in Retinal Pigment Epithelium Cell-Based Therapy for Retinal Disease.},
journal = {Stem cells translational medicine},
volume = {13},
number = {4},
pages = {317-331},
pmid = {38394392},
issn = {2157-6580},
mesh = {Humans ; Retinal Pigment Epithelium ; Stem Cell Transplantation/methods ; *Retinal Diseases/therapy ; Retina ; *Macular Degeneration/therapy ; },
abstract = {Age-related macular degeneration and retinitis pigmentosa are degenerative retinal diseases that cause severe vision loss. Early clinical trials involving transplantation of retinal pigment epithelial cells and/or photoreceptors as a treatment for these conditions are underway. In this review, we summarize recent progress in the field of retinal pigment epithelium transplantation, including some pertinent clinical trial results as well as preclinical studies that address issues of transplant immunology, cell delivery, and cell manufacturing.},
}
@article {pmid38393691,
year = {2024},
author = {Pan, F and Shu, Q and Xie, H and Zhao, L and Wu, P and Du, Y and Lu, J and He, Y and Wang, X and Peng, H},
title = {Protective effects of triptolide against oxidative stress in retinal pigment epithelium cells via the PI3K/AKT/Nrf2 pathway: a network pharmacological method and experimental validation.},
journal = {Aging},
volume = {16},
number = {4},
pages = {3955-3972},
pmid = {38393691},
issn = {1945-4589},
mesh = {Humans ; Reactive Oxygen Species/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; NF-E2-Related Factor 2/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Antioxidants/pharmacology/metabolism ; Retinal Pigment Epithelium ; Molecular Docking Simulation ; Network Pharmacology ; Oxidative Stress ; *Macular Degeneration/drug therapy/metabolism ; Apoptosis ; *Diterpenes ; Epoxy Compounds ; *Phenanthrenes ; },
abstract = {PURPOSE: Among aging adults, age-related macular degeneration (AMD), is a prevalent cause of blindness. Nevertheless, its progression may be halted by antioxidation in retinal pigment epithelium (RPE). The primary effective constituent of Tripterygium wilfordii Hook. F., triptolide (TP), has demonstrated anti-inflammatory, antiproliferative, and antioxidant properties. The mechanics of the protective effect of triptolide against the oxidative damage in retinal pigment epithelial (RPE) were assessed in this study.<br><br>METHODS: ARPE-19 cells were pretreated with TP, and then exposed to sodium iodate (SI). First, cell viability was assessed using CCK-8. Subsequently, we measured indicators for cell oxidation including reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Then, we used network pharmacological analysis and molecular docking to explore the signaling pathway of TP. Last, we used western blot, ELISA, and immunofluorescence assays to clarify the potential mechanistic pathways.<br><br>RESULTS: The network pharmacology data suggested that TP may inhibit AMD by regulating the PI3K/Akt signaling pathway. Experimental results showed that the potential mechanism is that it regulates the PI3K/Akt pathway and promotes Nrf2 phosphorylation and activation, thereby raising the level of antioxidant factors (HO-1, NQO1) and reducing the generation of ROS, which inhibit oxidative damage.<br><br>CONCLUSION: Our findings suggested that the effect of TP on SI-exposed RPE cells principally relies on the regulation of oxidative stress through the PI3K/Akt/Nrf2 signaling pathway.},
}
@article {pmid38393419,
year = {2024},
author = {Chen, J and Zhao, L and Zhang, L and Luo, Y and Jiang, Y and H, P},
title = {The identification of signature genes and their relationship with immune cell infiltration in age-related macular degeneration.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {339},
pmid = {38393419},
issn = {1573-4978},
support = {81670881//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Aged ; Animals ; Mice ; *Transforming Growth Factor beta2/genetics ; *Macular Degeneration/genetics ; Retina ; Blotting, Western ; RNA, Messenger ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made with anti-VEGF therapy, clinical outcomes have proven to be unsatisfactory.<br><br>METHOD: We obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from the GEO database. GO and KEGG analyses were used to enrich the DEGs. Weighted gene coexpression network analysis (WGCNA) was used to identify modules related to AMD. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were employed to screen hub genes. Gene set enrichment analysis (GSEA) was used to explore the pathways in which these hub genes were enriched. CIBERSORT was utilized to analyze the relationship between the hub genes and immune cell infiltration. Finally, Western blotting and RT&#x2012;PCR were used to explore the expression of hub genes in AMD mice.<br><br>RESULTS: We screened 1084 DEGs in GSE29801, of which 496 genes were upregulated. These 1084 DEGs were introduced into the WGCNA, and 94 genes related to AMD were obtained. Seventy-nine overlapping genes were obtained by the Venn plot. These 79 genes were introduced into three machine-learning methods to screen the hub genes, and the genes identified by the three methods were TNC, FAP, SREBF1, and TGF-&#x3b2;2. We verified their diagnostic function in the GSE29801 and GSE103060 datasets. Then, the hub gene co-enrichment pathways were obtained by GO and KEGG analyses. CIBERSORT analysis showed that these hub genes were associated with immune cell infiltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-&#x3b2;2 mRNA and protein in the retinas of AMD mice.<br><br>CONCLUSION: We found that four hub genes, namely, FAP, TGF-&#x3b2;2, SREBF1, and TNC, have diagnostic significance in patients with AMD and are related to immune cell infiltration. Finally, we determined that the mRNA and protein expression of these hub genes was upregulated in the retinas of AMD mice.},
}
@article {pmid38393321,
year = {2024},
author = {Kumar, P and Banik, SP and Ohia, SE and Moriyama, H and Chakraborty, S and Wang, CK and Song, YS and Goel, A and Bagchi, M and Bagchi, D},
title = {Current Insights on the Photoprotective Mechanism of the Macular Carotenoids, Lutein and Zeaxanthin: Safety, Efficacy and Bio-Delivery.},
journal = {Journal of the American Nutrition Association},
volume = {43},
number = {6},
pages = {505-518},
doi = {10.1080/27697061.2024.2319090},
pmid = {38393321},
issn = {2769-707X},
mesh = {Humans ; *Zeaxanthins/metabolism ; *Lutein/pharmacology/metabolism ; COVID-19/prevention &amp; control ; Antioxidants/pharmacology ; Macular Degeneration/metabolism/prevention &amp; control ; Macular Pigment/metabolism ; },
abstract = {Ocular health has emerged as one of the major issues of global health concern with a decline in quality of life in an aging population, in particular and rise in the number of associated morbidities and mortalities. One of the chief reasons for vision impairment is oxidative damage inflicted to photoreceptors in rods and cone cells by blue light as well as UV radiation. The scenario has been aggravated by unprecedented rise in screen-time during the COVID and post-COVID era. Lutein and Zeaxanthin are oxygenated carotenoids with proven roles in augmentation of ocular health largely by virtue of their antioxidant properties and protective effects against photobleaching of retinal pigments, age-linked macular degeneration, cataract, and retinitis pigmentosa. These molecules are characterized by their characteristic yellow-orange colored pigmentation and are found in significant amounts in vegetables such as corn, spinach, broccoli, carrots as well as fish and eggs. Unique structural signatures including tetraterpenoid skeleton with extensive conjugation and the presence of hydroxyl groups at the end rings have made these molecules evolutionarily adapted to localize in the membrane of the photoreceptor cells and prevent their free radical induced peroxidation. Apart from the benefits imparted to ocular health, lutein and zeaxanthin are also known to improve cognitive function, cardiovascular physiology, and arrest the development of malignancy. Although abundant in many natural sources, bioavailability of these compounds is low owing to their long aliphatic backbones. Under the circumstances, there has been a concerted effort to develop vegetable oil-based carriers such as lipid nano-emulsions for therapeutic administration of carotenoids. This review presents a comprehensive update of the therapeutic potential of the carotenoids along with the challenges in achieving an optimized delivery tool for maximizing their effectiveness inside the body.},
}
@article {pmid38389841,
year = {2024},
author = {Liang, Y and Kong, L and Zhang, Y and Zhang, Y and Shi, M and Huang, J and Kong, H and Qi, S and Yang, Y and Hong, J and Zhu, M and Zhu, X and Sun, X and Zhang, S and Wu, L and Zhao, C},
title = {Transfer RNA derived fragment, tRF-Glu-CTC, aggravates the development of neovascular age-related macular degeneration.},
journal = {Theranostics},
volume = {14},
number = {4},
pages = {1500-1516},
pmid = {38389841},
issn = {1838-7640},
mesh = {Humans ; Aged ; Angiogenesis Inhibitors/pharmacology ; Endothelial Cells/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/genetics ; *Choroidal Neovascularization/drug therapy ; Hypoxia/metabolism ; Cell Cycle Proteins/metabolism ; },
abstract = {Rationale: Angiogenesis expedites tissue impairment in many diseases, including age-related macular degeneration (AMD), a leading cause of irreversible blindness in elderly. A substantial proportion of neovascular AMD patients, characterized by aberrant choroidal neovascularization (CNV), exhibit poor responses or adverse reactions to anti-VEGF therapy. Herein, we aimed to unveil the function of newly identified transfer RNA-derived small RNA, tRF-Glu-CTC, in the pathology of CNV and determine its potential in inhibiting angiogenesis. Methods: Small non-coding RNA sequencing and quantitative polymerase chain reaction were conducted to detect expression pattern of tRF-Glu-CTC in CNV development. Immunofluorescence staining, fundus fluorescein angiography and ex vivo choroidal sprouting assays were employed for the evaluation of tRF-Glu-CTC's function in CNV development. The role of tRF-Glu-CTC in endothelial cells were determined by in vitro endothelial cell proliferation, migration and tube formation assays. Transcriptome sequencing, dual-luciferase reporter assay and in vitro experiments were conducted to investigate downstream mechanism of tRF-Glu-CTC mediated pathology. Results: tRF-Glu-CTC exhibited substantial up-regulation in AMD patients, laser-induced CNV model, and endothelial cells under hypoxia condition, which is a hallmark of CNV. Inhibiting tRF-Glu-CTC reduced angiogenesis and hypoxia stress in the neovascular region without neuroretina toxicity in laser-induced CNV model, showing an anti-angiogenic effect comparable to bevacizumab, while overexpression of tRF-Glu-CTC significantly augmented CNV. Mechanically, under hypoxia condition, angiogenin was involved in the production of tRF-Glu-CTC, which in turn triggered endothelial cell tubulogenesis, migration and promoted the secretion of inflammatory factors via the suppression of vasohibin 1 (VASH1). When downregulating VASH1 expression, the inhibition of tRF-Glu-CTC showed minimal suppression on angiogenesis. Conclusions: This study demonstrated the important role of tRF-Glu-CTC in the progression of angiogenesis. Targeting of tRF-Glu-CTC may be an alternative to current anti-VEGF therapy for CNV in AMD and other conditions with angiogenesis.},
}
@article {pmid38389327,
year = {2024},
author = {Carlo, C and Poddi, M and Mocini, S and Boni, N and Damiani, F and Battini, MA and Mirabella, G and Tataranno, M},
title = {Clinical evaluation of tear substitute utility after anti-VEGF intravitreal injection.},
journal = {European journal of ophthalmology},
volume = {34},
number = {6},
pages = {1847-1851},
doi = {10.1177/11206721241234427},
pmid = {38389327},
issn = {1724-6016},
mesh = {Humans ; *Intravitreal Injections ; Female ; Male ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Dry Eye Syndromes/drug therapy/diagnosis/physiopathology ; Surveys and Questionnaires ; Middle Aged ; Tears/chemistry ; Wet Macular Degeneration/drug therapy/diagnosis ; Hyaluronic Acid/administration &amp; dosage/adverse effects ; Lubricant Eye Drops/administration &amp; dosage ; Aged, 80 and over ; Ophthalmic Solutions ; Polyethylene Glycols/administration &amp; dosage ; },
abstract = {PURPOSE: The purpose of this study is to evaluate the role of a polyethylene glycol 400 - propylene glycol - hydroxypropyl guar - hyaluronic acid eye drops in relieving the symptoms of dry eye syndrome after anti-VEGF intravitreal injection.<br><br>METHODS: In this randomized, parallel-group study, patients were randomized to receive standard therapy alone or study eye drops plus standard therapy. Patients enrolled were older than 50 with exudative age-related macular degeneration, who have never had intravitreal injections, and without severe dry eye condition or severe ocular or systemic conditions. Patients had baseline preoperative evaluation (V0), and successively after 15 (V1) and 30 (V2) days. At VO and V1 T-BUT, Schirmer's test, fluorescein staining, DEQ5 and OSDI questionnaires were performed and at V2 (30) the OSDI questionnaire was administered.<br><br>RESULTS: 80 patients were included in the study, of them 40 received standard therapy plus study eye drops. DEQ5 questionnaire showed an increase in the control group between the values at V0 and V1, while in the study group a decrease was observed. No changes in T-BUT, Schirmer, and fluorescein staining values between V0 and V1 were observed in both groups. OSDI data in the control group showed no statistically significant differences, while in the study group they showed a statistically significant difference.<br><br>CONCLUSIONS: In our study patients undergoing for the first time intravitreal treatment presented dry eye symptoms in the postoperative period: in this group of patients the use of a tears substitute reduces postoperative ocular discomfort.},
}
@article {pmid38387875,
year = {2024},
author = {Diprose, WK and Wang, MTM and Reidy, J and Ma, A and Brodie, J and Steinfort, B},
title = {Ophthalmic artery stenosis on three-dimensional rotational angiography: Interrater agreement, prevalence, and risk factors.},
journal = {Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences},
volume = {},
number = {},
pages = {15910199241233020},
pmid = {38387875},
issn = {2385-2011},
abstract = {BACKGROUND: There is emerging interest in ophthalmic artery (OA) stenosis angioplasty for the treatment of age-related macular degeneration. Three-dimensional rotational angiography (3DRA) could be used during conventional angiography to determine the presence and severity of OA stenosis. In patients who had undergone 3DRA of the internal carotid artery, we aimed to assess the interrater agreement, prevalence, and risk factors for OA stenosis.<br><br>METHODS: Consecutive patients from two centers who had undergone conventional angiography with 3DRA of the internal carotid arteries were enrolled in this study. 3DRAs were independently double read for the presence of OA stenosis, as defined as narrowing of the proximal OA of at least 50% when compared to the more distal "normal" OA. Interrater agreement for the evaluation of OA stenosis was assessed with the Cohen's kappa coefficient. Univariate and multivariable logistic regression were used to identify potential predictors of OA stenosis.<br><br>RESULTS: Three hundred and two patients (97 men; mean&#x2009;&#xb1;&#x2009;SD 57.6&#x2009;&#xb1;&#x2009;13.4 years) were included in the analysis. Cohen's kappa coefficient (95% CI) was 0.877 (0.798-0.956). OA stenosis was present in 45 patients (14.9%). Multiple logistic regression demonstrated that female sex (odds ratio [OR]&#x2009;=&#x2009;2.70, 95% confidence interval [CI] 1.18-6.09, p&#x2009;=&#x2009;0.02) and smoking (OR&#x2009;=&#x2009;2.11, 95% CI 1.10-4.06, p&#x2009;=&#x2009;0.03) were significant risk factors for OA stenosis. Age, hypertension, diabetes, coronary artery disease, and subarachnoid hemorrhage were not associated with OA stenosis.<br><br>CONCLUSION: The evaluation of OA stenosis on 3DRA had excellent interrater agreement. OA stenosis was common and was associated with smoking and female sex.},
}
@article {pmid38387859,
year = {2024},
author = {Roca-Cabau, MA and Kumaran, N and Asencio-Durán, M and Pita-Ortiz, I and Dabad Moreno, JV},
title = {Pseudomelanoma diagnosis in a tertiary ophthalmologic centre in Spain.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {59},
number = {6},
pages = {e763-e767},
doi = {10.1016/j.jcjo.2024.01.017},
pmid = {38387859},
issn = {1715-3360},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; *Tomography, Optical Coherence/methods ; Spain/epidemiology ; Aged ; *Melanoma/diagnosis ; Adult ; Diagnosis, Differential ; *Uveal Neoplasms/diagnosis ; Tertiary Care Centers ; Aged, 80 and over ; Young Adult ; Diagnostic Errors ; Adolescent ; Choroid Neoplasms/diagnosis ; Fluorescein Angiography/methods ; Child ; Uveal Melanoma ; },
abstract = {OBJECTIVE: To determine the types and frequency of lesions that can be misdiagnosed as choroidal or ciliary body melanomas (posterior uveal tract melanoma [PUM]).<br><br>METHODS: This is a retrospective, descriptive study examining data from patients referred to Hospital La Paz in Madrid with the diagnosis of possible PUM between January 2005 and March 2020. All patients referred for PUM were studied. In collaboration with an oncology-specialized ophthalmologic centre, each patient underwent a full ophthalmic examination, ultrasonography, and optical coherence tomography, with agreed clinical criteria used to differentiate melanomas from pseudomelanomas.<br><br>RESULTS: In our cohort of 715 patients, 48.9% had pseudomelanomas. Thirty-five different conditions were misdiagnosed as melanomas. The 5 most common conditions were choroidal nevus (40.5%), peripheral exudative hemorrhagic chorioretinopathy (12%), choroidal hemangioma (10.5%), choroidal metastasis (8%), and age-related macular degeneration (4%).<br><br>CONCLUSIONS: Altering the diagnosis and changing the treatment and prognosis for patients can be difficult for a referral centre. Herein we present the largest European cohort investigated and highlight the importance of identifying the correct diagnosis to prevent mistreatment and possible overtreatment. These misdiagnoses can have an emotional effect on patients and their families, which could be avoided with a correct diagnosis. We analyze the most common pseudomelanoma diagnoses to help physicians better diagnose patients in their care.},
}
@article {pmid38386849,
year = {2024},
author = {Liu, C and Su, W and Jiang, X and Lv, Y and Kong, F and Chen, Q and Zhang, Q and Zhang, H and Liu, Y and Li, X and Xu, X and Chen, Y and Qu, D},
title = {A Sustainable Retinal Drug Co-Delivery for Boosting Therapeutic Efficacy in wAMD: Unveiling Multifaceted Evidence and Synergistic Mechanisms.},
journal = {Advanced healthcare materials},
volume = {13},
number = {14},
pages = {e2303659},
doi = {10.1002/adhm.202303659},
pmid = {38386849},
issn = {2192-2659},
support = {82173980//National Natural Science Foundation of China/ ; 81873017//National Natural Science Foundation of China/ ; BE2023788//Jiangsu Province Key Research and Development Program for Social Development Project/ ; BK20211389//Natural Science Foundation of Jiangsu Province of China/ ; ZD202322//Key Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; M2021010//General Project of Jiangsu Provincial Health Commission/ ; 2020YLXK015//Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine/ ; //333 project/ ; //Project 333 of Jiangsu Province/ ; YY-028-2019//Six Talent Peaks Project in Jiangsu Province/ ; },
mesh = {Animals ; *Pyrazines/chemistry/administration &amp; dosage/pharmacology/pharmacokinetics ; Retina/drug effects/metabolism ; Macular Degeneration/drug therapy ; Drug Delivery Systems/methods ; Humans ; Choroidal Neovascularization/drug therapy/metabolism/pathology ; Mice ; Hydrogels/chemistry/pharmacology ; Oxidative Stress/drug effects ; Camphanes/chemistry/pharmacology ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism ; },
abstract = {Sustainable retinal codelivery poses significant challenges technically, although it is imperative for synergistic treatment of wet age-related macular degeneration (wAMD). Here, a microemulsion-doped hydrogel (Bor/PT-M@TRG) is engineered as an intravitreal depot composing of temperature-responsive hydrogel (TRG) and borneol-decorated paeoniflorin (PF) &amp; tetramethylpyrazine (TMP)-coloaded microemulsions (Bor/PT-M). Bor/PT-M@TRG, functioning as the "ammunition depot", resides in the vitreous and continuously releases Bor/PT-M as the therapeutic "bullet", enabling deep penetration into the retina for 21 days. A single intravitreal injection of Bor/PT-M@TRG yields substantial reductions in choroidal neovascularization (CNV, a hallmark feature of wAMD) progression and mitigates oxidative stress-induced damage in vivo. Combinational PF&amp;TMP regulates the "reactive oxygen species/nuclear factor erythroid-2-related factor 2/heme oxygenase-1" pathway and blocks the "hypoxia inducible factor-1α/vascular endothelial growth factor" signaling in retina, synergistically cutting off the loop of CNV formation. Utilizing fluorescence resonance energy transfer and liquid chromatography-mass spectrometry techniques, they present compelling multifaceted evidence of sustainable retinal codelivery spanning formulations, ARPE-19 cells, in vivo eye balls, and ex vivo section/retina-choroid complex cell levels. Such codelivery approach is elucidated as the key driving force behind the exceptional therapeutic outcomes of Bor/PT-M@TRG. These findings highlight the significance of sustainable retinal drug codelivery and rational combination for effective treatment of wAMD.},
}
@article {pmid38386332,
year = {2024},
author = {Nam, J and Nivison-Smith, L and Trinh, M},
title = {Spatial Analysis Reveals Vascular Changes in Retinal and Choroidal Vessel Perfusion in Intermediate AMD With Reticular Pseudodrusen.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {2},
pages = {33},
pmid = {38386332},
issn = {1552-5783},
mesh = {Humans ; Cross-Sectional Studies ; Retrospective Studies ; Perfusion ; Retina ; *Retinal Drusen ; *Macular Degeneration ; *Diabetic Retinopathy ; *Cardiovascular Diseases ; },
abstract = {PURPOSE: To examine the effect of reticular pseudodrusen (RPD) on retinal and choroidal vessel perfusion (VP) topography in intermediate age-related macular degeneration (iAMD) using refined spatial analyses.<br><br>METHODS: This was a retrospective cross-sectional study of 120 individuals with 30 iAMDRPD, 60 iAMDno_RPD, and 30 normal eyes, propensity-score matched by age, sex, and presence of cardiovascular-related disease. VP of the superficial and deep retinal and choriocapillaris vascular slabs was assessed from 6 &#xd7; 6-mm optical coherence tomography angiography (OCTA) scans divided into 126 &#xd7; 126 grids, with adjustment for various person- and eye-level factors. Grid-wise VP differences (%) among the groups were spatially assessed according to analyses based on the Early Treatment for Diabetic Retinopathy Study (ETDRS), eccentricity (&#xb5;m), and degree (&#xb0;).<br><br>RESULTS: VP was significantly decreased between iAMDRPD and iAMDno_RPD, across all vascular slabs in various ETDRS sectors (up to -2.16%; 95% confidence interval, -2.99 to -1.34; P < 0.05). Eccentricity analyses revealed more complex patterns: a bisegmented relationship where VP in iAMDRPD eyes decreased linearly toward 1000&#xa0;&#xb5;m then returned toward similar values as iAMDno_RPD, plateauing around 2000 &#xb5;m in the superficial and 3000 &#xb5;m in the deep retina (R2 = 0.57-0.9; P < 0.001). Degree-based analysis further showed that the greatest VP differences in iAMDRPD eyes were commonly located superiorly and nasally across all vascular slabs (P < 0.05).<br><br>CONCLUSIONS: RPD appears to compound the vascular impact of iAMD, displaying complex spatial patterns beyond the ETDRS sectors. This highlights the importance of considering spatial delineations for future work regarding the role of RPD and vascular dysfunction.},
}
@article {pmid38386186,
year = {2024},
author = {Schuster, AK and Leisle, L and Picker, N and Bubendorfer-Vorwerk, H and Lewis, P and Hahn, P and Wasem, J and Finger, RP},
title = {Epidemiology of Diagnosed Age-related Macular Degeneration in Germany: An Evaluation of the Prevalence Using AOK PLUS Claims Data.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {4},
pages = {1025-1039},
pmid = {38386186},
issn = {2193-8245},
abstract = {INTRODUCTION: Epidemiologic data on age-related macular degeneration (AMD) are mainly based on cohort studies, including both diagnosed and undiagnosed cases. Using health claims data allows estimating epidemiological data of diagnosed subjects with AMD within the health care system using diagnosis codes from a regional claims database (AOK PLUS) to estimate the prevalence and incidence of non-exudative and exudative AMD in Germany.<br><br>METHODS: Patients with AMD were identified among AOK PLUS insured patients based on at least two outpatient, ophthalmologic or one inpatient H35.3 diagnoses for the years 2012 to 2021. Patients without continuous observation in a calendar year were excluded. Prevalence was assessed, and 1-year cumulative incidence was determined by the number of newly diagnosed patients divided by the number of individuals at risk. For 2020 and 2021, the AMD stage was assessed by diagnostic subcodes for non-exudative and exudative AMD, respectively. For 2012 to 2019, patient numbers were estimated based on the average proportions of non-exudative AMD and exudative AMD, respectively, in 2020 and 2021. Incidence and prevalence numbers were then extrapolated to Germany.<br><br>RESULTS: Between 2012 to 2021, the prevalence of diagnosed AMD cases remained relatively stable among approximately 3.27 million AOK PLUS insured persons, ranging from 0.96% (minimum in 2021) to 1.31% (maximum in 2014) for non-exudative AMD, about twice as high as for exudative AMD (min-max: 0.53-0.72%). The age- and sex-adjusted projections amounted to 644,153 diagnosed non-exudative and 367,086 diagnosed German patients with exudative AMDs in 2021. The 1-year cumulative incidence for non-exudative and exudative AMD, respectively, ranged from 122,427-142,932 to 46,092-86,785 newly diagnosed cases.<br><br>CONCLUSION: The number of diagnosed cases with AMD in Germany has increased slightly over the past decade. For the first time, patient counts with non-exudative and exudative AMD were approximated for Germany based on a representative, large-scale database study.},
}
@article {pmid38385315,
year = {2024},
author = {Kuzucu Üşümüş, SA and Koçak Altıntaş, AG and Özdemir, A and Aypak, C},
title = {Using the Amsler Grid Test for Age-Related Macular Degeneration Screening.},
journal = {Turkish journal of ophthalmology},
volume = {54},
number = {1},
pages = {11-16},
pmid = {38385315},
issn = {2149-8709},
mesh = {Humans ; Middle Aged ; Aged ; Visual Acuity ; *Visual Field Tests/methods ; *Macular Degeneration/diagnosis ; Sensitivity and Specificity ; Tomography, Optical Coherence ; },
abstract = {OBJECTIVES: To evaluate the use of the Amsler grid test (AGT) in screening for age-related macular degeneration (AMD), one of the most common causes of blindness, in primary healthcare settings.<br><br>MATERIALS AND METHODS: The AGT was applied to 700 eyes of 355 people aged 50 and over who applied to a family health center in Ankara and had no eye complaints. The test was considered positive if the lines on the AGT card were seen as broken or curved, there was a difference in shape or size between the squares, or a color change or blurring was described in any area. An ophthalmologist was consulted if the AGT was positive in one or both eyes. Patients considered suitable by ophthalmologists were evaluated with optical coherence tomography. AGT results were compared with ophthalmologist examination and tomography findings in terms of AMD detection.<br><br>RESULTS: The AGT was positive in 97 (13.9%) and negative in 603 (86.1%) out of 700 eyes included in the study. A total of 184 eyes, 79 with a positive AGT and 105 eyes with a negative test, were evaluated by an ophthalmologist. As a result of examinations and tests performed by ophthalmologists, AMD was detected in a total of 67 eyes: 42 of 79 eyes with positive AGT and 25 of 105 eyes with negative AGT but referred to an ophthalmologist for different reasons. In our study, the AGT had 62.7% sensitivity and 68.4% specificity.<br><br>CONCLUSION: The AGT is an inexpensive and easily applicable test. Although moderate sensitivity and specificity were found in our study; further studies are needed to evaluate the suitability of its use for AMD screening in primary care with limited facilities.},
}
@article {pmid38384637,
year = {2024},
author = {Dalai, R and Bedant, SS and Rout, R and Panda, BB},
title = {A Prospective Observational Study on Clinical Profile and Visual Outcomes in Neovascular Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {16},
number = {1},
pages = {e52731},
pmid = {38384637},
issn = {2168-8184},
abstract = {Background and objectives Over the years, several treatment options have been developed for neovascular age-related macular degeneration (AMD), the most notable being intravitreal injections of anti-vascular endothelial growth factor drugs. The rationale for treating neovascular AMD is to preserve and improve central vision, enhance the quality of life for affected individuals, stabilize or improve vision, and prevent further structural damage to the macula. The objective of the present study was to evaluate the clinical course of different disease types of neovascular age-related macular degeneration and their treatment response to anti-vascular endothelial growth factor (anti-VEGF) injections. Methods This prospective observational study was conducted at a tertiary care referral hospital in Eastern India during October 2019 and September 2021. Patients diagnosed with neovascular AMD attending our Outpatient department and retina clinic were recruited for the study. An experienced ophthalmologist examined all patients, meeting the inclusion criteria. The clinical profile, including initial best corrected visual acuity (BCVA), ophthalmoscopic, fluorescein angiographic, and optical coherence tomography (OCT) findings of different patterns of neovascular AMD, were collected and analyzed. Patients were subjected to intravitreal Ranibizumab every month for three months and then on a when-required basis. Visual outcomes were recorded at each follow-up, and a comparison was done between initial and final visual acuity. Descriptive statistics were used for analysis, with p< 0.05 taken as statistically significant. Results A total of 72 patients were included in the study. Fundus fluorescein angiography revealed that 52.78% were classic, 15.28% were minimally classic, and 31.94% were of occult variety. 41.66% of lesions were subfoveal in location, 47.22% were juxtafoveal, and 11.11% lesions were extrafoveal in location. The mean BCVA was Log MAR (Logarithm of the Minimum Angle of Resolution) 1.061±0.25. The average number of intravitreal Ranibizumab injections given to each eye was five. BCVA of patients after the third injection was log MAR 0.818±0.296. There was a significant improvement in mean BCVA from baseline 1.061±0.254 to 0.787±0.317 after the study (p-valve: p<0.05). After the first injection, 49 patients (68.05%) experienced an initial improvement of at least one line, 20 patients (27.77%) did not exhibit any improvement, and 3 patients (4.16%) had a decline of one line in Snellen's visual acuity chart. Over the follow-up period,10 showed improvement in 1 line in the Snellen chart after subsequent injection. At the end of the study, six patients showed no change, and four patients showed deterioration after the completion of injections. No adverse events were noted during the study period. Conclusions Intravitreal Ranibizumab is effective in improving visual outcomes in treatment-naïve individuals with neovascular age-related macular degeneration. The decision for repeat intravitreal anti-VEGF injection should be based on OCT findings of subretinal fluid, pigment epithelial detachment, and cystoid macular edema as an indicator of disease activity. This can also lessen the number of intravitreal injections and morbidity in these patients.},
}
@article {pmid38383835,
year = {2024},
author = {Wang, L and Wang, C and Li, L and Zhou, X and Hua, X and Yuan, X},
title = {Analysis of the Molecular Mechanism of Xueshuantong in the Treatment of Wet Age-Related Macular Degeneration (AMD) Using GEO Datasets, Network Pharmacology, and Molecular Docking.},
journal = {Biochemical genetics},
volume = {62},
number = {6},
pages = {5004-5021},
pmid = {38383835},
issn = {1573-4927},
support = {No. 81670817//National Natural Science Foundation of China/ ; 81870638//National Natural Science Foundation of China/ ; },
mesh = {*Molecular Docking Simulation ; Humans ; *Network Pharmacology ; *Drugs, Chinese Herbal/therapeutic use/chemistry/pharmacology ; *Wet Macular Degeneration/drug therapy/genetics ; Protein Interaction Maps ; Vascular Endothelial Growth Factor A/genetics/metabolism/antagonists &amp; inhibitors ; },
abstract = {At present, the main treatment method for wet AMD is single anti-VEGF therapy, which can require multiple injections, is costly and may have poor efficacy. Studies and clinical experiments have shown that the oral Chinese medicine Xueshuantong combined with anti-VEGF therapy is more effective, and this study aims to explore the molecular mechanism. The TCMSP database was used to identify the main Xueshuantong components. The PubChem database and SWISS Target Prediction data were used to find the SMILES molecular formulas of compounds and corresponding target genes and disease-related genes were searched using the GEO, DisGeNET, and GeneCards databases. Venny was used to identify the intersecting wet AMD-related genes and Xueshuantong targets and Cytoscape software was used to construct direct links between the drug components and disease targets. Then, PPI networks were constructed using the STRING website. R software was used for GO and KEGG enrichment analyses. Cytoscape software was used for topological analyses, and AutoDock Vina v.1.1.2 software was used for molecular docking. 64 compounds corresponding to four drugs were found by the TCMSP database, 1001 total drug targets were found by the PubChem database, 607 wet AMD target genes were found by the GEO, DisGeNET, and GeneCards databases, and 87 Xueshuantong target genes for wet AMD were obtained. Then, by constructing the drug component and disease target network and PPI network, we found that the components closely interacted with VEGF, TNF, caspase 3, CXCL8, and AKT1, which suggested that the therapeutic effects might be related to the inhibition of neovascularization, inflammation, and AKT pathway. Then, GO enrichment analysis showed that the biological processes response to hypoxia, positive regulation of angiogenesis, and inflammatory response were enriched. KEGG enrichment results showed that the HIF-1 and pi3k-akt pathways may mediate the inhibition of wet AMD by Xueshuantong. Topological analysis results identified 10 key proteins, including VEGF, TNF, AKT1, and TLR4. The results of molecular docking also confirmed their strong binding to their respective compounds. In this study, it was confirmed that Xueshuantong could inhibit wet AMD by targeting VEGF, TNF, TLR4, and AKT1, multichannel HIF-1, and the PI3K-AKT pathway, which further proved the therapeutic effects of Xueshuantong combined with single anti-VEGF therapy on wet AMD and provided new insights into the study of novel molecular drug targets for the treatment of wet AMD.},
}
@article {pmid38383077,
year = {2024},
author = {Chen, ZJ and Ng, DS and Ho, M and Lu, SY and Tam, POS and Young, AL and Brelen, ME and Yam, JC and Tham, CC and Pang, CP and Chen, LJ},
title = {Genetic associations of central serous chorioretinopathy subtypes, neovascular age-related macular degeneration, and polypoidal choroidal vasculopathy.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {1},
pages = {100003},
doi = {10.1016/j.apjo.2023.100003},
pmid = {38383077},
issn = {2162-0989},
mesh = {Humans ; Genotype ; *Central Serous Chorioretinopathy/genetics ; Polypoidal Choroidal Vasculopathy ; Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics ; *Choroidal Neovascularization/genetics ; Fluorescein Angiography ; },
abstract = {PURPOSE: To evaluate the genetic associations of different subtypes of central serous chorioretinopathy (CSCR), neovascular age-related macular degeneration (nAMD), and polypoidal choroidal vasculopathy (PCV).<br><br>DESIGN: A case-control genetic association study.<br><br>METHODS: This study enrolled 217 CSCR, 341 nAMD, 288 PCV patients, and 1380 controls. The CSCR patients were classified into those with focal or diffuse leakage, with or without pigment epithelial detachment (PED), and with or without macular neovascularization (MNV). Associations between 11 variants from 8 genes, ADAMTS9, ANGPT2, ARMS2, CFH, NR3C2, PGF, TNFRSF10A and VIPR2, and diseases/subtypes were analyzed by logistic regression analysis adjusted for age and sex, and inter-phenotype comparison by heterogeneity test.<br><br>RESULTS: The CFH rs800292-A conferred a protective effect for CSCR with MNV (OR=0.44, P&#xa0;=&#xa0;0.002) and a risk effect for CSCR without MNV (OR=1.31, P&#xa0;=&#xa0;0.023). CSCR patients carrying rs800292-G had a 3.23-fold of increased risk towards developing secondary MNV (P&#xa0;=&#xa0;1.45&#xa0;&#xd7;10[-4]). CFH rs3753394, rs800292 and rs1329428 showed similar effects among CSCR with MNV, nAMD and PCV, but opposite effects on CSCR without MNV. TNFRSF10A rs13278062-T was associated with overall CSCR but not with CSCR subtypes, nAMD or PCV. Moreover, CFH and ARMS2 SNPs showed heterogeneous effects in CSCR without MNV against CSCR with MNV, nAMD and PCV.<br><br>CONCLUSIONS: Genetic associations of CSCR with MNV resembled nAMD and PCV compared to CSCR without MNV, indicating differential genetic effects on neovascularization and choroidopathy. Further investigation of the functional roles of CFH, ARMS2, and TNFRSF10A in CSCR, nAMD and PCV should help elucidate the mechanisms of these maculopathies.},
}
@article {pmid38383074,
year = {2024},
author = {Chen, J and Zhang, S and Yang, F and Jiang, Y and Lu, Y and Tang, Y},
title = {Prevalence and causes of vision impairment in elderly Chinese people living in suburban Shanghai.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {1},
pages = {100002},
doi = {10.1016/j.apjo.2023.100002},
pmid = {38383074},
issn = {2162-0989},
mesh = {Aged ; Humans ; *Blindness/epidemiology/etiology ; *Cataract/complications/epidemiology ; China/epidemiology ; Cross-Sectional Studies ; *East Asian People ; *Macular Degeneration/complications/epidemiology ; Prevalence ; *Vision Disorders/epidemiology/etiology ; *Vision, Low/epidemiology/etiology ; },
abstract = {PURPOSE: To investigate the current prevalence and causes of moderate and severe visual impairment (MSVI) and blindness in elderly people in suburban Shanghai, China.<br><br>METHODS: A cross-sectional study based on the population was conducted, which involved 5846 individuals (11,692 eyes) aged 65 years or older. Thorough eye examinations were performed to assess the prevalence and leading factors of MSVI (BCVA <20/63 to &#x2265;20/400) and blindness (BCVA <20/400).<br><br>RESULTS: The standardized prevalence of bilateral MSVI and blindness was 3.3% and 0.6%, correspondingly. The standardized prevalence of monocular MSVI and blindness was 7.4% and 2.0%, correspondingly. Cataract (47.9% and 20.7%, correspondingly) and myopic macular degeneration (MMD, 25.7% and 31.1%, correspondingly) were the principal causes of bilateral MSVI and blindness. As for monocular MSVI, the primary causes were cataract (39.4%), age-related macular degeneration (AMD, 16.6%), and MMD (16.6%). The primary causes of monocular blindness were other posterior segment eye diseases (30.1%) and MMD (14.2%). In adults aged 65-74 years, MMD was the foremost factor causing bilateral vision impairment. Conversely, cataract was identified as the primary cause of bilateral and monocular vision impairment among adults aged &#x2265;&#xa0;75 years. AMD accounts for a significant proportion of individuals across all age groups.<br><br>CONCLUSIONS: The significant prevalence of MSVI and blindness among Chinese adults represents a critical public health issue. In addition to cataract, the vision impairment caused by MMD and AMD become an important issue in the elderly Chinese people.},
}
@article {pmid38382813,
year = {2024},
author = {Khanani, AM and Kotecha, A and Chang, A and Chen, SJ and Chen, Y and Guymer, R and Heier, JS and Holz, FG and Iida, T and Ives, JA and Lim, JI and Lin, H and Michels, S and Quezada Ruiz, C and Schmidt-Erfurth, U and Silverman, D and Singh, R and Swaminathan, B and Willis, JR and Tadayoni, R and , },
title = {TENAYA and LUCERNE: Two-Year Results from the Phase 3 Neovascular Age-Related Macular Degeneration Trials of Faricimab with Treat-and-Extend Dosing in Year 2.},
journal = {Ophthalmology},
volume = {131},
number = {8},
pages = {914-926},
doi = {10.1016/j.ophtha.2024.02.014},
pmid = {38382813},
issn = {1549-4713},
mesh = {Humans ; Male ; Female ; *Visual Acuity/physiology ; *Intravitreal Injections ; Double-Blind Method ; *Antibodies, Bispecific/administration &amp; dosage/adverse effects/therapeutic use ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Middle Aged ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use/adverse effects ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Angiopoietin-2/antagonists &amp; inhibitors ; Treatment Outcome ; Tomography, Optical Coherence ; Follow-Up Studies ; Aged, 80 and over ; Fluorescein Angiography ; Dose-Response Relationship, Drug ; },
abstract = {PURPOSE: To evaluate 2-year efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A.<br><br>DESIGN: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials.<br><br>PARTICIPANTS: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older.<br><br>METHODS: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen.<br><br>MAIN OUTCOME MEASURES: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112.<br><br>RESULTS: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n&#xa0;= 555 faricimab; n&#xa0;= 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change,&#xa0;+3.7 letters [95% confidence interval (CI),&#xa0;+2.1 to&#xa0;+5.4] and&#xa0;+3.3 letters [95% CI,&#xa0;+1.7 to&#xa0;+4.9], respectively; mean difference, +0.4 letters [95% CI,&#xa0;-1.9 to&#xa0;+2.8]) and LUCERNE (adjusted mean change,&#xa0;+5.0 letters [95% CI,&#xa0;+3.4 to&#xa0;+6.6] and&#xa0;+5.2 letters [95% CI,&#xa0;+3.6 to&#xa0;+6.8], respectively; mean difference,&#xa0;-0.2 letters [95% CI,&#xa0;-2.4 to&#xa0;+2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week&#xa0;112.<br><br>CONCLUSIONS: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38380547,
year = {2024},
author = {Shang, X and Liu, J and Zhu, Z and Zhang, X and Huang, Y and Liu, S and Wang, W and Zhang, X and Ma, S and Tang, S and Hu, Y and Ge, Z and Yu, H and He, M},
title = {Metabolomic age and risk of 50 chronic diseases in community-dwelling adults: A prospective cohort study.},
journal = {Aging cell},
volume = {23},
number = {5},
pages = {e14125},
pmid = {38380547},
issn = {1474-9726},
support = {KJ012019530//High level Talent Flexible Introduction Fund of Guangdong Provincial Peoples Hospital/ ; },
mesh = {Humans ; Middle Aged ; Chronic Disease ; Prospective Studies ; Aged ; Male ; Female ; Adult ; *Independent Living ; Risk Factors ; Metabolomics ; },
abstract = {It is unclear how metabolomic age is associated with the risk of a wide range of chronic diseases. Our analysis included 110,692 participants (training: n = 27,673; testing: n = 27,673; validating: n = 55,346) aged 39-71 years at baseline (2006-2010) from the UK Biobank. Incident chronic diseases were identified using inpatient records, or death registers until January 2021. Predicted metabolomic age was trained and tested based on 168 metabolomics. Metabolomic age was linked to the risk of 50 diseases in the validation dataset. The median follow-up duration for individual diseases ranged from 11.2 years to 11.9 years. After controlling for false discovery rate, chronological age-adjusted age gap (CAAG) was significantly associated with the incidence of 25 out of 50 chronic diseases. After adjustment for full covariates, associations with 15 chronic diseases remained significant. Greater CAAG was associated with increased risk of eight cardiometabolic disorders (including cardiovascular diseases and diabetes), some cancers, alcohol use disorder, chronic obstructive pulmonary disease, chronic kidney disease, chronic liver disease and age-related macular degeneration. The association between CAAG and risk of peripheral vascular disease, other cardiac diseases, fracture, cataract and thyroid disorder was stronger among individuals with unhealthy diet than in those with healthy diet. The association between CAAG and risk of some conditions was stronger in younger individuals, those with metabolic disorders or low education. Metabolomic age plays an important role in the development of multiple chronic diseases. Healthy diet and high education may mitigate the risk for some chronic diseases due to metabolomic age acceleration.},
}
@article {pmid38376852,
year = {2024},
author = {Kikushima, W and Sakurada, Y and Fukuda, Y and Matsubara, M and Yoneyama, S and Shijo, T and Sugiyama, A and Kotoda, Y and Kashiwagi, K},
title = {INCIDENCE AND CHARACTERISTICS OF NEOVASCULAR AGE-RELATED MACULAR WITH OVER A 12-MONTH REMISSION AFTER THREE MONTHLY AFLIBERCEPT ADMINISTRATION: 60 Months Results of a Pro Re Nata Regimen.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {3},
pages = {498-505},
doi = {10.1097/IAE.0000000000003994},
pmid = {38376852},
issn = {1539-2864},
mesh = {Humans ; Infant ; Incidence ; Clinical Protocols ; *Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins ; },
abstract = {PURPOSE: To investigate the characteristics of patients with over a 12-month remission after 3 monthly intravitreal aflibercept injections followed by a pro re nata regimen for exudative age-related macular degeneration (AMD).<br><br>METHODS: One hundred forty-four eyes with exudative AMD were included. All patients received 3 monthly intravitreal aflibercept injections as a loading dose, followed by an as-needed regimen for 60 months. Patients were classified into the remission and recurrence groups depending on the presence or absence of a 12-month remission. ARMS2 A69S and CFH I62V were genotyped in all cases.<br><br>RESULTS: During the study, 82 eyes (56.9%) showed 12 months or more remission at least once. The cumulative incidence rate of a 12-month remission showed a plateau pattern and converged to 60% (y = -166.26x-2.172 + 0.6, R2 = 0.8168). Patients in the remission group were younger than those in the recurrence group (P < 0.001) and had less risk allele frequency of the ARMS2 gene than the recurrence group (P < 0.001). The longer the remission interval was prolonged, the better visual acuity was achieved at the 60-month visit (P < 0.001).<br><br>CONCLUSION: Fifty-seven percent of patients showed a 12-month remission or more at least once during a 60-month follow-up, suggesting that patients with no reactivation can prolong the treatment interval.},
}
@article {pmid38375484,
year = {2024},
author = {Qiu, X and Huang, MN and Ping, S},
title = {Genetic susceptibility and causal pathway analysis of eye disorders coexisting in multiple sclerosis.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1337528},
pmid = {38375484},
issn = {1664-3224},
mesh = {Humans ; *Cataract ; Genetic Predisposition to Disease ; *Macular Degeneration ; *Multiple Sclerosis/epidemiology/genetics/complications ; *Optic Neuritis/epidemiology/genetics ; Mendelian Randomization Analysis ; },
abstract = {INTRODUCTION: The comorbidity of optic neuritis with multiple sclerosis has been well recognized. However, the causal association between multiple sclerosis and optic neuritis, as well as other eye disorders, remains incompletely understood. To address these gaps, we investigated the genetically relationship between multiple sclerosis and eye disorders, and explored potential drugs.<br><br>METHODS: In order to elucidate the genetic susceptibility and causal links between multiple sclerosis and eye disorders, we performed two-sample Mendelian randomization analyses to examine the causality between multiple sclerosis and eye disorders. Additionally, causal single-nucleotide polymorphisms were annotated and searched for expression quantitative trait loci data. Pathway enrichment analysis was performed to identify the possible mechanisms responsible for the eye disorders coexisting with multiple sclerosis. Potential therapeutic chemicals were also explored using the Cytoscape.<br><br>RESULTS: Mendelian randomization analysis revealed that multiple sclerosis increased the incidence of optic neuritis while reducing the likelihood of concurrent of cataract and macular degeneration. Gene Ontology enrichment analysis implicated that lymphocyte proliferation, activation and antigen processing as potential contributors to the pathogenesis of eye disorders coexisting with multiple sclerosis. Furthermore, pharmaceutical agents traditionally employed for allograft rejection exhibited promising therapeutic potential for the eye disorders coexisting with multiple sclerosis.<br><br>DISCUSSION: Multiple sclerosis genetically contributes to the development of optic neuritis while mitigating the concurrent occurrence of cataract and macular degeneration. Further research is needed to validate these findings and explore additional mechanisms underlying the comorbidity of multiple sclerosis and eye disorders.},
}
@article {pmid38374754,
year = {2024},
author = {Zheng, C and Zeng, R and Wu, G and Hu, Y and Yu, H},
title = {Beyond Vision: A View from Eye to Alzheimer's Disease and Dementia.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {11},
number = {2},
pages = {469-483},
doi = {10.14283/jpad.2023.118},
pmid = {38374754},
issn = {2426-0266},
mesh = {Humans ; *Alzheimer Disease/diagnosis/epidemiology/complications ; Brain/pathology ; Aging ; *Eye Diseases/diagnosis/epidemiology/complications ; },
abstract = {With the aging of the global population, the health care burden of Alzheimer's disease (AD) and dementia is considered to increase dramatically in the coming decades. Given the insufficiency of effective interventions for AD and dementia, clinical research on identifying potentially modifiable risk factors and early diagnostic biomarkers becomes a public health priority. Currently, extracerebral manifestations with a large proportion of ocular involvement are usually recognized to precede the symptoms of AD and dementia. Growing epidemiologic evidence also suggests that eye disorders, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy, and so on, are closely associated with and even have a higher incidence of AD and dementia. The eye, as an extension of the central nervous system, therefore has the potential to provide a feasible approach to detecting structural and functional abnormalities of the brain. Numerous new imaging modalities are developed and give novel insights into the detection of several neurodegenerative, vascular, neuropathological, and other ocular abnormalities of AD and dementia in scientific research and clinical application. This review provides an overview of the epidemiologic associations between eye disorders and AD or dementia and summarizes the recent advances in ocular examinations and techniques employed for the detection of AD and dementia. With more brain-and-eye interconnections being identified, the eye is becoming a noninvasive and easily accessible window for the early diagnosis and prevention of AD and dementia.},
}
@article {pmid38374365,
year = {2024},
author = {Van Vu, K and Mitchell, P and Detaram, HD and Burlutsky, G and Liew, G and Gopinath, B},
title = {Prevalence and risk factors for impaired activities of daily living in patients with neo-vascular age-related macular degeneration who present for anti-VEGF treatment.},
journal = {Eye (London, England)},
volume = {38},
number = {9},
pages = {1647-1653},
pmid = {38374365},
issn = {1476-5454},
support = {n/a//Macular Disease Foundation Australia (MDFA)/ ; },
mesh = {Humans ; *Activities of Daily Living ; Male ; Female ; Aged ; Prevalence ; *Angiogenesis Inhibitors/therapeutic use ; Risk Factors ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; *Visual Acuity/physiology ; Wet Macular Degeneration/drug therapy/epidemiology/physiopathology ; Quality of Life ; Ranibizumab/administration &amp; dosage/therapeutic use ; Intravitreal Injections ; Middle Aged ; Cross-Sectional Studies ; },
abstract = {BACKGROUND/OBJECTIVES: To assess the prevalence and correlates of impaired activities of daily living (ADLs) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (VEGF) therapy.<br><br>METHODS: In a clinic-based cohort of 437 patients with nAMD who presented for anti-VEGF therapy, the Older American Resources and Services Scale (OARS) was administered to assess for impairments in basic, instrumental and total ADL. Logistic regression analyses were conducted to determine odds ratios (OR) and 95% confidence intervals (CI) for factors associated with ADL impairment.<br><br>RESULTS: The prevalence of impaired basic, instrumental and total ADL was 37.76%, 67.82% and 39.59%, respectively. In multivariate-adjusted models, moderate visual impairment [OR 5.65, 95% CI (2.31-13.83) and blindness [OR 5.43, 95% CI (2.09-14.12)] were associated with greater odds of impaired total ADL. Depressive symptoms [OR 2.08, 95% CI (1.08-4.00)], the presence of any disability [OR 3.16, 95% CI (1.64-0.07)] and never driving [OR 4.00, 95% CI (1.60-10.00)] were also positively associated with total ADL impairment. Better vision-related quality of life (QoL) was inversely associated with impaired instrumental ADL whilst higher health-related QoL scores were associated with decreased odds of total ADL impairment.<br><br>CONCLUSIONS: There is a high prevalence rate of ADL impairment among nAMD patients presenting for therapy. Visual impairment, never driving, poor physical and mental health increased the odds of experiencing ADL impairment whilst better VRQoL and HRQoL reduced the odds of impairment.},
}
@article {pmid38371465,
year = {2024},
author = {Thananjeyan, AL and Siu, A and Jennings, A and Bala, C},
title = {Extended Depth-of-Focus Intraocular Lens Implantation in Patients with Age-Related Macular Degeneration: A Pilot Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {451-458},
pmid = {38371465},
issn = {1177-5467},
abstract = {PURPOSE: To assess visual outcomes of the implantation of a non-diffractive extended depth of focus (EDOF) intraocular lens (IOL) in patients with age-related macular degeneration (AMD).<br><br>SETTING: Ophthalmology practice, Sydney, Australia.<br><br>DESIGN: Retrospective chart review.<br><br>METHODS: Patients with AMD undergoing cataract surgery and receiving non-diffractive EDOF AcrySof IQ Vivity IOL implantation over a 2-year period were identified. Corrected distance visual acuity (CDVA), distance-corrected near visual acuity (DCNVA; 50 cm), contrast sensitivity, central foveal thickness, VF-14 questionnaire results, and quality of life where available were analyzed.<br><br>RESULTS: A total of 28 sequential patients (51 eyes) were included in this pilot study (46% male, mean age 77.4 years). Of 27 eyes that had late AMD, 17 (63%) had wet AMD. Mean patient preoperative CDVA was logMAR 0.32&#xb1;0.29. Postoperative monocular CDVA and DCNVA were logMAR 0.20&#xb1;0.25 and N9&#xb1;5 (range N5-N36), respectively. Eyes achieving postoperative CDVA of Snellen 6/5-6/12 (n=42, 82%), 6/15-6/24 (n=7, 14%), and greater than 6/24 (n=2, 4%) achieved a mean DCNVA of N8 (range N5-N10), N13 (range N10-N18), and N27 (range N18-N36), respectively. Eyes achieving CDVA of Snellen 6/5-6/12 showed contrast sensitivity within the normal range. On postoperative VF-14 questionnaire, patients with CDVA of Snellen 6/5-6/12 reported minimal visual impairment, while patients with CDVA greater than 6/15 reported mild impairment. A majority of patients (96%, n=27) were satisfied with the improvement in quality of life postoperatively. No intraoperative complications were reported.<br><br>CONCLUSION: The EDOF AcrySof IQ Vivity IOL provides improved near vision proportional to distance vision in patients with early AMD.},
}
@article {pmid38371267,
year = {2024},
author = {Liu, R and Xuan, M and Wang, DC and Xiao, O and Guo, XX and Zhang, J and Wang, W and Jong, M and Sankaridurg, P and Ohno-Matsui, K and Yin, QX and He, MG and Li, ZX},
title = {Using choroidal thickness to detect myopic macular degeneration.},
journal = {International journal of ophthalmology},
volume = {17},
number = {2},
pages = {317-323},
pmid = {38371267},
issn = {2222-3959},
abstract = {AIM: To explore the usage of choroidal thickness measured by swept-source optical coherence tomography (SS-OCT) to detect myopic macular degeneration (MMD) in high myopic participants.<br><br>METHODS: Participants with bilateral high myopia (&#x2264;-6 diopters) were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study. SS-OCT was performed to determine the choroidal thickness, and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia (META-PM) Classi&#xfb01;cation. Presence of MMD was defined as META-PM category 2 or above.<br><br>RESULTS: A total of 568 right eyes were included for analysis. Eyes with MMD (n=106, 18.7%) were found to have older age, longer axial lengths (AL), higher myopic spherical equivalents (SE), and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study (ETDRS) grid sector (P<0.001). The area under the receiver operating characteristic (ROC) curves (AUC) for subfoveal choroidal thickness (0.907) was greater than that of the model, including age, AL, and SE at 0.6249, 0.8208, and 0.8205, respectively. The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD (AUC of 0.928 and 0.923, respectively). An outer nasal sector choroidal thickness of less than 74 &#xb5;m demonstrated the highest odds of predicting MMD (OR=33.8).<br><br>CONCLUSION: Choroidal thickness detects the presence of MMD with high agreement, particularly of the inner and outer nasal sectors of the posterior pole, which appears to be a biometric parameter more precise than age, AL, or SE.},
}
@article {pmid38370915,
year = {2024},
author = {Owsley, C and Swain, TA and Kar, D and Curcio, CA},
title = {Rod mediated dark adaptation, a functional test for early and intermediate AMD outcomes.},
journal = {Expert review of ophthalmology},
volume = {19},
number = {1},
pages = {1-5},
pmid = {38370915},
issn = {1746-9899},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY006109/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
}
@article {pmid38369283,
year = {2024},
author = {Rowen, D and Carlton, J and Terheyden, JH and Finger, RP and Wickramasekera, N and Brazier, J and , },
title = {Development and Valuation of a Preference-Weighted Measure in Age-Related Macular Degeneration From the Vision Impairment in Low Luminance Questionnaire: A MACUSTAR Report.},
journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research},
volume = {27},
number = {5},
pages = {642-654},
doi = {10.1016/j.jval.2024.02.001},
pmid = {38369283},
issn = {1524-4733},
mesh = {Humans ; *Macular Degeneration/psychology/physiopathology ; Female ; Male ; Aged ; Surveys and Questionnaires ; *Psychometrics ; *Patient Preference ; Germany ; United Kingdom ; Middle Aged ; Aged, 80 and over ; Quality of Life ; },
abstract = {OBJECTIVES: This study generates VILL-UI (Vision Impairment in Low Luminance - Utility Index), a preference-weighted measure (PWM) derived from the VILL-33 measure for use in patients with age-related macular degeneration (AMD) and valued to generate United Kingdom and German preference weights.<br><br>METHODS: A PWM consists of a classification system to describe health and utility values for every state described by the classification. The classification was derived using existing data collected as part of the MACUSTAR study, a low-interventional study on AMD, conducted at 20 clinical sites across Europe. Items were selected using psychometric and Rasch analyses, published criteria around PWM suitability, alongside instrument developer views and concept elicitation work that informed VILL-33 development. An online discrete choice experiment (DCE) with duration of the health state was conducted with the United Kingdom and German public. Responses were modeled to generate utility values for all possible health states.<br><br>RESULTS: The classification system has 5 items across the 3 domains of VILL-33: reading and accessing information, mobility and safety, and emotional well-being. The DCE samples (United Kingdom: n&#xa0;= 1004, Germany: n&#xa0;= 1008) are broadly representative and demonstrate good understanding of the tasks. The final DCE analyses produce logically consistent and significant coefficients.<br><br>CONCLUSIONS: This study enables responses to VILL-33 to be directly used to inform economic evaluation in AMD. The elicitation of preferences from both United Kingdom and Germany enables greater application of VILL-UI for economic evaluation throughout Europe. VILL-UI fills a gap in AMD in which generic preference-weighted measures typically lack sensitivity.},
}
@article {pmid38369214,
year = {2024},
author = {Hung, JH and Tsai, PH and Aala, WJF and Chen, CC and Chiou, SH and Wong, TW and Tsai, KJ and Hsu, SM and Wu, LW},
title = {TIMP3/Wnt axis regulates gliosis of Müller glia.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1870},
number = {4},
pages = {167087},
doi = {10.1016/j.bbadis.2024.167087},
pmid = {38369214},
issn = {1879-260X},
mesh = {Animals ; Humans ; Mice ; beta Catenin/genetics/metabolism ; *Diabetic Retinopathy/metabolism ; Gliosis/metabolism ; Mice, Inbred C57BL ; Neuroglia/metabolism ; Retina/metabolism ; *Retinal Diseases/metabolism ; Tissue Inhibitor of Metalloproteinase-3/genetics/metabolism ; },
abstract = {BACKGROUND: Previous studies have confirmed the expression of tissue inhibitor of metalloproteinase-3 (TIMP3) in Müller glia (MG). However, the role of TIMP3 in MG remains unknown.<br><br>METHODS: A mouse model of laser-induced retinal damage and gliosis was generated using wild-type C57BL/6 mice. TIMP3 and associated proteins were detected using Western blotting and immunofluorescence microscopy. RNA sequencing (GSE132140) of mouse laser-induced gliosis was utilized for pathway analysis. TIMP3 overexpression was induced in human MG. Human vitreous samples were obtained from patients with proliferative diabetic retinopathy (PDR) and healthy controls for protein analysis.<br><br>RESULTS: TIMP3 levels increased in mouse eyes after laser damage. Morphology and spatial location of TIMP3 indicated its presence in MG. TIMP3-overexpressing MG showed increased cellular proliferation, migration, and cell nuclei size, suggesting TIMP3-induced gliosis for retinal repair. Glial fibrillary acidic protein (GFAP) and vimentin levels were elevated in TIMP3-overexpressing MG and laser-damaged mouse retinas. RNA sequencing and Western blotting suggested a role for &#x3b2;-catenin in mediating TIMP3 effects on the retina. Human vitreous samples from patients with PDR showed a positive correlation between TIMP3 and GFAP levels, both of which were elevated in patients with PDR.<br><br>CONCLUSIONS: TIMP3 is associated with MG gliosis to enhance the repair ability of damaged retinas and is mediated by the canonical Wnt/&#x3b2;-catenin. Changes in TIMP3 could potentially be used to control gliosis in a range of retinal diseases However, given the multifaceted nature of TIMP3, care must be taken when developing treatments that aim solely to boost the function of TIMP3.<br><br>FUNDING: National Cheng Kung University Hospital, Taiwan (NCKUH-10604009 and NCKUH-11202007); the Ministry of Science and Technology (MOST 110-2314-B-006-086-MY3).},
}
@article {pmid38369100,
year = {2024},
author = {Liu, D and Liu, Z and Liao, H and Chen, ZS and Qin, B},
title = {Ferroptosis as a potential therapeutic target for age-related macular degeneration.},
journal = {Drug discovery today},
volume = {29},
number = {4},
pages = {103920},
doi = {10.1016/j.drudis.2024.103920},
pmid = {38369100},
issn = {1878-5832},
mesh = {Humans ; *Ferroptosis ; *Macular Degeneration/drug therapy ; Cell Death ; Lipid Peroxides ; Neurons ; },
abstract = {Cell death plays a crucial part in the process of age-related macular degeneration (AMD), but its mechanisms remain elusive. Accumulating evidence suggests that ferroptosis, a novel form of regulatory cell death characterized by iron-dependent accumulation of lipid hydroperoxides, has a crucial role in the pathogenesis of AMD. Numerous studies have suggested that ferroptosis participates in the degradation of retinal cells and accelerates the progression of AMD. Furthermore, inhibitors of ferroptosis exhibit notable protective effects in AMD, underscoring the significance of ferroptosis as a pivotal mechanism in the death of retinal cells during the process of AMD. This review aims to summarize the molecular mechanisms of ferroptosis in AMD, enumerate potential inhibitors and discuss the challenges and future opportunities associated with targeting ferroptosis as a therapeutic strategy, providing important information references and insights for the prevention and treatment of AMD.},
}
@article {pmid38368762,
year = {2024},
author = {Uzzan, J and Haddad, M and Salamé, N},
title = {[Quality of life survey of 3,738 patients treated with intravitreal injections for age-related macular degeneration].},
journal = {Journal francais d'ophtalmologie},
volume = {47},
number = {3},
pages = {104075},
doi = {10.1016/j.jfo.2024.104075},
pmid = {38368762},
issn = {1773-0597},
mesh = {Humans ; Female ; Male ; Intravitreal Injections ; *Quality of Life ; Cross-Sectional Studies ; Povidone-Iodine/adverse effects ; *Macular Degeneration/drug therapy/epidemiology ; },
abstract = {PURPOSE: To evaluate the peri- and post-intravitreal injection (IVI) symptoms reported by patients who have been repeatedly injected for age-related macular degeneration (AMD) and to analyze these according to the protocols of the injector.<br><br>MATERIALS AND METHODS: Multi-center, cross-sectional, consecutive, analytical survey.<br><br>RESULTS: The IVI protocols of 106 injectors differed in terms of the number of instillations of povidone-iodine, its contact time, and rinsing of the ocular surface post-injection. In total, 3,738 patients responded to the survey, 60.1% of whom were women; 36.4% had received more than 20 IVIs; 50.7% of patients reported irritation upon application of povidone-iodine. Post-IVI, depending on the symptom in question, between 44.8% and 57.4% of patients reported symptoms of ocular surface change. The number of instillations of povidone-iodine, its contact time with the ocular surface, and abundant rinsing post-IVI increased the immediate symptoms. Patients who received more IVIs were more prone to experiencing gritty eyes, and the incidence of acute pain increased in patients who had previously received over 20 IVIs. Women and patients previously treated for dry eye or glaucoma were at greater risk of worse symptoms.<br><br>CONCLUSION: Comparing injecting centers' practices with patients' self-assessments showed an aggravation of symptoms of ocular surface changes related to povidone-iodine. This survey contributes to providing data for the implementation of a protocol to improve the quality of life of patients injected repeatedly for AMD.},
}
@article {pmid38365648,
year = {2024},
author = {Vofo, BN and Saada, M and Rivera, A and Cohen, S and Jaouni, T and Khateb, S},
title = {Disease quiescence in endophthalmitis patients treated with anti-VEGF injections for retinal pathologies.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {73},
pmid = {38365648},
issn = {1471-2415},
mesh = {Female ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors ; Bevacizumab/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; *Retinal Vein Occlusion/drug therapy ; *Choroidal Neovascularization/drug therapy ; Intravitreal Injections ; *Endophthalmitis/etiology/complications ; },
abstract = {BACKGROUND: The most feared complication of intravitreal injections is the development of endophthalmitis, which could lead to irreversible visual loss. The aim of this study was to characterize the clinical profiles, causative pathogens, and clinical outcome of patients post-endophthalmitis.<br><br>METHODS: Retrospective, single center case series study. Clinical records, causative pathogens and management of all cases of endophthalmitis post intravitreal anti-vascular endothelial growth factor (VEGF) injections recorded between January 1st, 2006 and May 30th, 2022; were retrieved. The visual and anatomic changes prior to the episode of endophthalmitis and up to 2 years post-treatment were compared.<br><br>RESULTS: Eleven post-injection endophthalmitis eyes of 10 patients (n&#x2009;=&#x2009;3 females; 30%) were recruited at mean age of 64.5&#x2009;&#xb1;&#x2009;20.4 years. The median last recorded BCVA, up to 3 months prior to the episode of endophthalmitis was 60 (Interquartile range (IQR) 55-75) ETDRS letters. Then, it dropped to 30 (IQR 0-57.5), 35 (IQR 0-52.5) and 35 (IQR 0-57.5) ETDRS letters at presentation, 6- and 12-months follow-up; respectively (p&#x2009;=&#x2009;0.027, p&#x2009;=&#x2009;0.017 and p&#x2009;=&#x2009;0.012). However, at 24 months, the median BCVA returned to similar baseline values prior to the episode of endophthalmitis; BCVA 50 (IQR 0-60) ETDRS letters, p&#x2009;=&#x2009;0.062. Interestingly, two eyes with neovascular age-related macular degeneration (NVAMD), 1 with myopic choroidal neovascularization (CNV) and 1 with retinal vein occlusion (RVO), experienced disease quiescence and did not require additional anti-VEGF injections up to 2 years of follow-up.<br><br>CONCLUSION: This study demonstrates long-term recovery of vision loss due to endophthalmitis post anti-VEGF injections, regained up to 2 years later. It also indicates that disease quiescence post endophthalmitis may not only occur in eyes treated for NVAMD, but also with myopic CNV and RVO.},
}
@article {pmid38365085,
year = {2024},
author = {Becker, S and L'Ecuyer, Z and Jones, BW and Zouache, MA and McDonnell, FS and Vinberg, F},
title = {Modeling complex age-related eye disease.},
journal = {Progress in retinal and eye research},
volume = {100},
number = {},
pages = {101247},
pmid = {38365085},
issn = {1873-1635},
support = {R00 EY031737/EY/NEI NIH HHS/United States ; R01 EY015128/EY/NEI NIH HHS/United States ; R01 EY028927/EY/NEI NIH HHS/United States ; R01 EY031706/EY/NEI NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY034986/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Aging/physiology ; *Disease Models, Animal ; Disease Progression ; *Glaucoma/physiopathology/genetics ; *Macular Degeneration/genetics/physiopathology ; Humans ; },
abstract = {Modeling complex eye diseases like age-related macular degeneration (AMD) and glaucoma poses significant challenges, since these conditions depend highly on age-related changes that occur over several decades, with many contributing factors remaining unknown. Although both diseases exhibit a relatively high heritability of >50%, a large proportion of individuals carrying AMD- or glaucoma-associated genetic risk variants will never develop these diseases. Furthermore, several environmental and lifestyle factors contribute to and modulate the pathogenesis and progression of AMD and glaucoma. Several strategies replicate the impact of genetic risk variants, pathobiological pathways and environmental and lifestyle factors in AMD and glaucoma in mice and other species. In this review we will primarily discuss the most commonly available mouse models, which have and will likely continue to improve our understanding of the pathobiology of age-related eye diseases. Uncertainties persist whether small animal models can truly recapitulate disease progression and vision loss in patients, raising doubts regarding their usefulness when testing novel gene or drug therapies. We will elaborate on concerns that relate to shorter lifespan, body size and allometries, lack of macula and a true lamina cribrosa, as well as absence and sequence disparities of certain genes and differences in their chromosomal location in mice. Since biological, rather than chronological, age likely predisposes an organism for both glaucoma and AMD, more rapidly aging organisms like small rodents may open up possibilities that will make research of these diseases more timely and financially feasible. On the other hand, due to the above-mentioned anatomical and physiological features, as well as pharmacokinetic and -dynamic differences small animal models are not ideal to study the natural progression of vision loss or the efficacy and safety of novel therapies. In this context, we will also discuss the advantages and pitfalls of alternative models that include larger species, such as non-human primates and rabbits, patient-derived retinal organoids, and human organ donor eyes.},
}
@article {pmid38361503,
year = {2024},
author = {Lei, S and Hu, M and Wei, Z},
title = {Identification of systemic biomarkers and potential drug targets for age-related macular degeneration.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1322519},
pmid = {38361503},
issn = {1663-4365},
abstract = {PURPOSE: Since age-related macular degeneration (AMD) is tightly associated with aging and cellular senescence, objective of this study was to investigate the association between plasma levels of senescence-related proteins (SRPs) and risk of AMD.<br><br>DESIGN: The whole study was based on two-sample Mendelian randomization (MR) analysis.<br><br>METHODS: For MR analysis, the primary approach for MR analysis was the inverse-variance weighted (IVW) method and the heterogeneity and pleiotropy of results were tested. The instrumental single-nucleotide polymorphisms (SNPs) associated with 110 SRPs were filtered and selected from a large genome-wide association study (GWAS) for plasma proteome involving 35,559 participants. The GWAS data of AMD was obtained from FinnGen consortium (6,157 AMD cases and 288,237 controls) and further validated by using data from UK Biobank consortium (3,553 AMD cases and 147,089 controls).<br><br>RESULTS: The MR results at both discovery and validation stages supported the causality (IVW-P < 0.00045) between plasma levels of 4 SRPs (C3b, CTNNB1, CCL1, and CCL3L1) and the risk of AMD and supported potential causality (IVW-P < 0.05) between other 10 SRPs and risk of AMD. No heterogeneity or pleiotropy in these results was detected.<br><br>CONCLUSION: Our findings supported that high plasma levels of C3b, CTNNB1, CCL1, and CCL3L1 were associated with increased risk of AMD, thereby highlighting the role of systemic inflammation in AMD pathogenesis and providing the rationale for developing new preventative and therapeutic strategies.},
}
@article {pmid38361015,
year = {2024},
author = {Weber, C and Tedt, J and Husser, O and Holz, FG and Liegl, R},
title = {[Survey on blood thinning therapy in patients with age-related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {121},
number = {3},
pages = {216-222},
pmid = {38361015},
issn = {2731-7218},
mesh = {Humans ; Aged, 80 and over ; *Anticoagulants/adverse effects ; Platelet Aggregation Inhibitors/adverse effects ; Retinal Hemorrhage/chemically induced ; Surveys and Questionnaires ; *Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: Patients with age-related macular degeneration (AMD) often receive concomitant systemic blood thinning medications. These are known to increase the risk of severe hemorrhage also in connection with AMD, which can lead to extensive subretinal hemorrhaging.<br><br>OBJECTIVE: The purpose of this study was to investigate the proportion of patients with AMD and concomitant blood thinning treatment, including the type and reason for blood thinning treatment.<br><br>METHODS: This survey was prospectively conducted at the University Eye Hospital, Bonn, Germany. Volunteers were recruited during retinal consultations and the consultations for intravitreal injections (IVOM).<br><br>RESULTS: The questionnaire was completed by 178 patients. The mean age was 81.7 years (58-100) and 101 patients (57.7%) were undergoing blood thinning treatment. The majority of patients were taking antiplatelet agents (n&#x202f;=&#x2009;59; 58.4%), especially ASA (n&#x202f;=&#x2009;55; 54.5%). Direct oral anticoagulants (DOAC) were taken by 33&#xa0;patients (32.7%), including most frequently apixaban (17.8%). Vitamin&#xa0;K antagonists (VKA) was taken by 4&#xa0;patients (4%). The most common reason for blood thinning treatment was atrial fibrillation (n&#x202f;=&#x2009;32, 31.7%), followed by stent implantation (n&#x202f;=&#x2009;20, 19.8%) and stroke (n&#x202f;=&#x2009;12, 11.9%) but 13 patients (12.9%) did not know why they were undergoing blood thinning treatment. No clear indications for the use of blood thinners were found in 31&#xa0;patients (30.7%).<br><br>CONCLUSION: A&#xa0;large proportion of patients with AMD undergo blood thinning treatment; however, not every patient has a&#xa0;clear indication. Due to the increased risk of bleeding, the use of blood thinners should be critically evaluated in close cooperation with primary care physicians and cardiologists.},
}
@article {pmid38360819,
year = {2024},
author = {Shah, SV and Singh, SR and Selvam, A and Harihar, S and Parmar, Y and Mangla, R and Arora, S and Vupparaboina, KK and Venkatesh, R and Chhablani, J},
title = {Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {18},
pmid = {38360819},
issn = {2056-9920},
abstract = {PURPOSE: To compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months.<br><br>METHODS: This was a retrospective chart review of treatment-na&#xef;ve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F).<br><br>RESULTS: A total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p&#x2009;>&#x2009;0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p&#x2009;<&#x2009;0.001 and PCV, r&#x2009;=&#x2009;-&#x2009;0.06; p&#x2009;=&#x2009;0.74) and the need for fewer anti-VEGF injections (n-AMD, r&#x2009;=&#x2009;-&#x2009;0.53; p&#x2009;<&#x2009;0.001 and PCV, r&#x2009;=&#x2009;-&#x2009;0.09; p&#x2009;=&#x2009;0.58).<br><br>CONCLUSION: PEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.},
}
@article {pmid38360182,
year = {2024},
author = {Yordi, S and Cakir, Y and Cetin, H and Talcott, KE and Srivastava, SK and Hu, J and Ehlers, JP},
title = {Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration from a Phase III Clinical Trial.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {8},
pages = {754-764},
doi = {10.1016/j.oret.2024.02.007},
pmid = {38360182},
issn = {2468-6530},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Dose-Response Relationship, Drug ; Double-Blind Method ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; Intravitreal Injections ; Prospective Studies ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors/administration &amp; dosage ; Recombinant Fusion Proteins/administration &amp; dosage ; *Retinal Detachment/diagnosis/drug therapy/etiology ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis/complications ; },
abstract = {OBJECTIVE: To evaluate the incidence of bacillary layer detachment in patients with neovascular age-related macular degeneration (nAMD) and their response to anti-VEGF therapy.<br><br>DESIGN: Post hoc analysis of the brolucizumab 6-mg and aflibercept 2-mg arms from the HAWK clinical trial, a 48-week, prospective, double-masked, phase III trial.<br><br>PARTICIPANTS: Participants (n&#xa0;= 652 and 652 eyes) randomized to brolucizumab 6-mg and aflibercept 2-mg arms from HAWK (NCT02307682).<br><br>METHODS: Spectral-domain OCT scans were obtained at 4-week intervals throughout the HAWK trial and segmented automatically using a proprietary, machine learning-enabled, higher-order feature extraction platform.<br><br>MAIN OUTCOME MEASURES: The incidence of bacillary layer detachment and effect of anti-VEGF therapy in these eyes on best-corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid volumes, subretinal hyper-reflective material (SHRM) volume, and ellipsoid zone (EZ) integrity from baseline to week&#xa0;48.<br><br>RESULTS: Classic bacillary layer detachment was identified in 7.2% (47/652) of eyes, demonstrating worse BCVA and higher CST, EZ total attenuation, subretinal fluid (SRF), and SHRM volume at baseline than eyes without bacillary layer detachment. Anti-VEGF treatment resulted in resolution of bacillary layer detachment in 97.9% of eyes by week 48. In eyes with bacillary layer detachment, anti-VEGF treatment improved BCVA and decreased SRF and SHRM volume; however, eyes with bacillary layer detachment never reached the level of BCVA improvement as eyes without bacillary layer detachment. A greater proportion of eyes with bacillary layer detachment had high-exudative volatility (increased mean standard deviation after loading dose) of CST, SRF, and total fluid than eyes without bacillary layer detachment (P < 0.05 for each comparison).<br><br>CONCLUSIONS: Bacillary layer detachment, an OCT signature representing photoreceptor schisis, is identifiable in a notable proportion of eyes with nAMD. Anti-VEGF therapy resulted in a very high proportion of bacillary layer detachment resolution with significantly decreased SRF and SHRM volumes. The majority of eyes with bacillary layer detachment have high-exudative volatility, which may be associated with lower BCVA outcomes. The presence of bacillary layer detachment may provide an important imaging biomarker to be considered for clinical trial inclusion/exclusion based on trial design and therapeutic goals because of its unique behavior.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38358437,
year = {2024},
author = {El Ghazi, D and Miere, A and Crincoli, E and Le, HM and Souied, EH},
title = {In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.},
journal = {International ophthalmology},
volume = {44},
number = {1},
pages = {82},
pmid = {38358437},
issn = {1573-2630},
mesh = {Female ; Male ; Humans ; Aged ; *Retinal Cone Photoreceptor Cells ; *Retina ; Tomography, Optical Coherence ; Ophthalmoscopy ; Health Status ; },
abstract = {PURPOSE: To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging.<br><br>METHODS: Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30&#xb0; retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD.<br><br>RESULTS: Mean age was 75.17&#x2009;&#xb1;&#x2009;2.51&#xa0;years in the SDD group (3 males, 3 females) versus 73.17&#x2009;&#xb1;&#x2009;3.15&#xa0;years in the healthy control group (p&#x2009;=&#x2009;0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean&#x2009;&#xb1;&#x2009;standard deviation foci detected (i.e., cone photoreceptors) was 7123.75&#x2009;&#xb1;&#x2009;3683.32&#xa0;foci/mm[2] in the SDD group versus 13,253&#x2009;&#xb1;&#x2009;3331.00&#xa0;foci/mm[2] in the healthy control group (p&#x2009;=&#x2009;0.0003). The number of SDD was associated with a reduction in foci density, p&#x2009;=&#x2009;0.0055, r&#x2009;=&#x2009;-&#x2009;0.7622.<br><br>CONCLUSION: The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.},
}
@article {pmid38356865,
year = {2024},
author = {Heo, JI and Ryu, J},
title = {Exosomal noncoding RNA: A potential therapy for retinal vascular diseases.},
journal = {Molecular therapy. Nucleic acids},
volume = {35},
number = {1},
pages = {102128},
pmid = {38356865},
issn = {2162-2531},
abstract = {Exosomes are extracellular vesicles that can contain DNA, RNA, proteins, and metabolites. They are secreted by cells and play a regulatory role in various biological responses by mediating cell-to-cell communication. Moreover, exosomes are of interest in developing therapies for retinal vascular disorders because they can deliver various substances to cellular targets. According to recent research, exosomes can be used as a strategy for managing retinal vascular diseases, and they are being investigated for therapeutic purposes in eye conditions, including glaucoma, dry eye syndrome, retinal ischemia, diabetic retinopathy, and age-related macular degeneration. However, the role of exosomal noncoding RNA in retinal vascular diseases is not fully understood. Here, we reviewed the latest research on the biological role of exosomal noncoding RNA in treating retinal vascular diseases. Research has shown that noncoding RNAs, including microRNAs, circular RNAs, and long noncoding RNAs play a significant role in the regulation of retinal vascular diseases. Furthermore, through exosome engineering, the expression of relevant noncoding RNAs in exosomes can be controlled to regulate retinal vascular diseases. Therefore, this review suggests that exosomal noncoding RNA could be considered as a biomarker for diagnosis and as a therapeutic target for treating retinal vascular disease.},
}
@article {pmid38352084,
year = {2024},
author = {Durmaz Engin, C and Karti, O and Kandemir, K},
title = {Subretinal Drusenoid Deposits in a Patient With HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet) Syndrome.},
journal = {Cureus},
volume = {16},
number = {1},
pages = {e52239},
pmid = {38352084},
issn = {2168-8184},
abstract = {Subretinal drusenoid deposits (SDD) are findings that can be observed in age-related macular degeneration as well as in ischemic ocular diseases. These deposits are believed to be of prognostic importance, as they have been shown to be associated with choroidal neovascularization. HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome is a condition linked with severe preeclampsia, and it presents ocular findings such as hypertensive retinopathy, serous retinal detachment, and cortical visual impairment. This case report discusses the presence and course of SDD in a female patient who presented with hypertensive retinochoroidopathy secondary to HELLP syndrome.},
}
@article {pmid38351484,
year = {2024},
author = {Lee, KH and Lee, SC and Lee, MW},
title = {Vitreous Opacity Following Intravitreal Brolucizumab Injection: A Case Series Review.},
journal = {Korean journal of ophthalmology : KJO},
volume = {38},
number = {2},
pages = {113-121},
pmid = {38351484},
issn = {2092-9382},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; *Vision Disorders ; *Orbital Diseases ; Pain ; Angiogenesis Inhibitors ; *Antibodies, Monoclonal, Humanized ; },
abstract = {PURPOSE: To investigate cases of vitreous opacity (VO) similar to asteroid hyalosis (AH) after intravitreal brolucizumab injection.<br><br>METHODS: A retrospective chart review was conducted to identify cases showing VO similar to AH among patients who received intravitreal brolucizumab injections at our retinal clinic from January 2022 to January 2023.<br><br>RESULTS: A total of 220 brolucizumab injections were administered at our hospital. VO, showing yellow-white brilliant reflective particles, was found in six patients (2.7%). When VO occurred, all patients complained of floaters, although none of them complained of other symptoms including decreased visual acuity, pain, or conjunctival redness. The mean number of brolucizumab injections was 2.57 &#xb1; 2.38. No significant visual impairment was observed while VO was present. VO improved in all cases, and four cases improved without any treatment. The mean interval from onset to disappearance of VO was 8.0 &#xb1; 3.1 weeks.<br><br>CONCLUSIONS: VO, similar to AH, can occur with a relatively high probability after intravitreal brolucizumab injections. Patients complained of severe floaters, but VO was not accompanied by other symptoms including vision impairment, injection, and pain. The VO disappeared after approximately 4 to 14 weeks. In case that other inflammatory findings are not severe, close follow-up without treatment may be sufficient. If a patient complains of floaters after an intravitreal brolucizumab injection, close fundus observation is necessary to evaluate the VO.},
}
@article {pmid38349778,
year = {2024},
author = {Naik, P and Grebe, R and Bhutto, IA and McLeod, DS and Edwards, MM},
title = {Histologic and Immunohistochemical Characterization of GA-Like Pathology in the Rat Subretinal Sodium Iodate Model.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {2},
pages = {10},
pmid = {38349778},
issn = {2164-2591},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY031044/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Rats ; Animals ; *Geographic Atrophy ; Retina ; Retinal Pigment Epithelium/pathology ; Iodates ; *Retinal Degeneration/chemically induced/pathology ; },
abstract = {PURPOSE: Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration with multifactorial etiology and no well-established treatment. A model recapitulating the hallmarks would serve as a key to understanding the underlying pathologic mechanisms better. In this report, we further characterized our previously reported subretinal sodium iodate model of GA.<br><br>METHODS: Retinal degeneration was induced in rats (6-8&#xa0;weeks old) by subretinal injections of NaIO3 as described previously. Animals were sacrificed at 3, 8 and 12&#xa0;weeks after injection and eyes were fixed or cryopreserved. Some choroids were processed as flatmounts while other eyes were cryopreserved, sectioned, and immunolabeled with a panel of antibodies. Finally, some eyes were prepared for transmission electron microscopic (TEM) analysis.<br><br>RESULTS: NaIO3 subretinal injection resulted in a well-defined focal area of retinal pigment epithelium (RPE) degeneration surrounded by viable RPE. These atrophic lesions expanded over time. RPE morphologic changes at the border consisted of hypertrophy, multilayering, and the possible development of a migrating phenotype. Immunostaining of retinal sections demonstrated external limiting membrane descent, outer retinal tubulation (ORT), and extension of M&#xfc;ller cells toward RPE forming a glial membrane in the subretinal space of the atrophic area. TEM findings demonstrated RPE autophagy, cellular constituents of ORT, glial membranes, basal laminar deposits, and defects in Bruch's membrane.<br><br>CONCLUSIONS: In this study, we showed pathologic features of a rodent model resembling human GA in a temporal order through histology, immunofluorescence, and TEM analysis and gained insights into the cellular and subcellular levels of the GA-like phenotypes.<br><br>TRANSLATIONAL RELEVANCE: Despite its acute nature, the expansion of atrophy and the GA-like border in this rat model makes it ideal for studying disease progression and provides a treatment window to test potential therapeutics for GA.},
}
@article {pmid38349420,
year = {2024},
author = {Cho, HJ and Kim, M and Kim, J and Yoon, I and Park, S and Kim, CG},
title = {Factors associated with the development of exudation in treatment-naive eyes with nonexudative macular neovascularization.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {7},
pages = {2073-2082},
pmid = {38349420},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; Aged ; *Visual Acuity ; Follow-Up Studies ; *Fundus Oculi ; Risk Factors ; Retinal Neovascularization/diagnosis/etiology ; Exudates and Transudates ; Macula Lutea/pathology ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Wet Macular Degeneration/diagnosis/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Intravitreal Injections ; Time Factors ; Subretinal Fluid ; },
abstract = {PURPOSE: To identify the predictive factors for development of exudation in patients with treatment-naïve nonexudative macular neovascularization (MNV).<br><br>METHODS: We retrospectively analyzed 61 treatment-na&#xef;ve patients with nonexudative MNV who had not received treatment for nonexudative MNV before the exudation developed. Baseline characteristics and changes in MNV were evaluated using multivariate modeling to determine the potential risk factors for exudative conversion.<br><br>RESULTS: Exudation development was identified in 31.1% (19/61 eyes) of the study eyes during the 46.2&#x2009;&#xb1;&#x2009;8.2-month mean follow-up period. The mean period of development of exudation from the baseline was 21.5&#x2009;&#xb1;&#x2009;6.7&#xa0;months. Multivariate Cox regression analysis identified that older age (hazard ratio [HR] of 1.380, 95% confidence interval [CI] 1.129-1.688, P&#x2009;=&#x2009;0.008), larger MNV area at baseline (HR of 1.715, CI 1.288-2.308; P&#x2009;=&#x2009;0.006), increase of MNV area by doubling (HR of 4.992, CI 1.932-9.246; P&#x2009;=&#x2009;0.002), and retinal pigment epithelium (RPE) elevation more than 100&#xa0;&#x3bc;m (HR of 1.017, CI 1.006-1.233; P&#x2009;=&#x2009;0.015) were associated with increased risk of the development of exudation.<br><br>CONCLUSION: Older age, larger MNV area, increasing MNV area, and higher RPE elevation were associated with an increased risk of exudative conversion in patients with treatment-na&#xef;ve nonexudative MNV. Identifying these risk factors may be helpful in establishing treatment strategies and monitoring patients.},
}
@article {pmid38349309,
year = {2024},
author = {Baqué-Vidal, L and Main, H and Petrus-Reurer, S and Lederer, AR and Beri, NE and Bär, F and Metzger, H and Zhao, C and Efstathopoulos, P and Saietz, S and Wrona, A and Jaberi, E and Willenbrock, H and Reilly, H and Hedenskog, M and Moussaud-Lamodière, E and Kvanta, A and Villaescusa, JC and La Manno, G and Lanner, F},
title = {Clinically compliant cryopreservation of differentiated retinal pigment epithelial cells.},
journal = {Cytotherapy},
volume = {26},
number = {4},
pages = {340-350},
doi = {10.1016/j.jcyt.2024.01.014},
pmid = {38349309},
issn = {1477-2566},
mesh = {Humans ; Aged ; Cell Differentiation ; *Pluripotent Stem Cells ; *Macular Degeneration/therapy ; Cryopreservation ; Epithelial Cells ; Retinal Pigments ; },
abstract = {BACKGROUND AIMS: Age-related macular degeneration (AMD) is the most common cause of blindness in elderly patients within developed countries, affecting more than 190 million worldwide. In AMD, the retinal pigment epithelial (RPE) cell layer progressively degenerates, resulting in subsequent loss of photoreceptors and ultimately vision. There is currently no cure for AMD, but therapeutic strategies targeting the complement system are being developed to slow the progression of the disease.<br><br>METHODS: Replacement therapy with pluripotent stem cell-derived (hPSC) RPEs is an alternative treatment strategy. A cell therapy product must be produced in accordance with Good Manufacturing Practices at a sufficient scale to facilitate extensive pre-clinical and clinical testing. Cryopreservation of the final cell product is therefore highly beneficial, as the manufacturing, pre-clinical and clinical testing can be separated in time and location.<br><br>RESULTS: We found that mature hPSC-RPE cells do not survive conventional cryopreservation techniques. However, replating the cells 2-5 days before cryopreservation facilitates freezing. The replated and cryopreserved hPSC-RPE cells maintained their identity, purity and functionality as characteristic RPEs, shown by cobblestone morphology, pigmentation, transcriptional profile, RPE markers, transepithelial resistance and pigment epithelium-derived factor secretion. Finally, we showed that the optimal replating time window can be tracked noninvasively by following the change in cobblestone morphology.<br><br>CONCLUSIONS: The possibility of cryopreserving the hPSC-RPE product has been instrumental in our efforts in manufacturing and performing pre-clinical testing with the aim for clinical translation.},
}
@article {pmid38348408,
year = {2023},
author = {Seddon, JM and De, D and Casazza, W and Cheng, SY and Punzo, C and Daly, M and Zhou, D and Coss, SL and Atkinson, JP and Yu, CY},
title = {Risk and protection of different rare protein-coding variants of complement component C4A in age-related macular degeneration.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1274743},
pmid = {38348408},
issn = {1664-8021},
support = {R01 AR073311/AR/NIAMS NIH HHS/United States ; R01 EY011309/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; },
abstract = {Introduction: Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly. One-third of the genetic contribution to this disease remains unexplained. Methods: We analyzed targeted sequencing data from two independent cohorts (4,245 cases, 1,668 controls) which included genomic regions of known AMD loci in 49 genes. Results: At a false discovery rate of <0.01, we identified 11 low-frequency AMD variants (minor allele frequency <0.05). Two of those variants were present in the complement C4A gene, including the replacement of the residues that contribute to the Rodgers-1/Chido-1 blood group antigens: [VDLL1207-1210ADLR (V1207A)] with discovery odds ratio (OR) = 1.7 (p = 3.2 × 10[-5]) which was replicated in the UK Biobank dataset (3,294 cases, 200,086 controls, OR = 1.52, p = 0.037). A novel variant associated with reduced risk for AMD in our discovery cohort was P1120T, one of the four C4A-isotypic residues. Gene-based tests yielded aggregate effects of nonsynonymous variants in 10 genes including C4A, which were associated with increased risk of AMD. In human eye tissues, immunostaining demonstrated C4A protein accumulation in and around endothelial cells of retinal and choroidal vasculature, and total C4 in soft drusen. Conclusion: Our results indicate that C4A protein in the complement activation pathways may play a role in the pathogenesis of AMD.},
}
@article {pmid38347957,
year = {2024},
author = {Chatzimichail, E and Pfau, K and Gatzioufas, Z and Panos, GD},
title = {Ranibizumab Biosimilars in Treating Retinal Disorders: A Cost-Effective Revolution?.},
journal = {Drug design, development and therapy},
volume = {18},
number = {},
pages = {365-374},
pmid = {38347957},
issn = {1177-8881},
mesh = {Infant, Newborn ; Humans ; Ranibizumab/therapeutic use ; *Biosimilar Pharmaceuticals/adverse effects ; Vascular Endothelial Growth Factor A ; Angiogenesis Inhibitors/therapeutic use ; *Diabetic Retinopathy/drug therapy ; Cost-Benefit Analysis ; *Macular Edema/drug therapy ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Antibodies, Monoclonal, Humanized/therapeutic use ; Intravitreal Injections ; Randomized Controlled Trials as Topic ; },
abstract = {Ranibizumab, is a humanized, monoclonal antibody fragment that binds and inactivates vascular endothelial growth factor-A (VEGF-A) and VEGF-B. One of the main indications for an intravitreal treatment with ranibizumab is age-related macular degeneration (AMD), which is a retinal disease with a high worldwide socioeconomic impact. Biosimilars constitute biological products that demonstrate similar pharmacodynamic and pharmacokinetic characteristics with a reference product, as well as comparable clinical efficacy, safety and immunogenicity. Since the approval of the first biosimilar Razumab, there has been a variety of new biosimilars available on the market. They offer the advantage of the same good clinical and safety results at a better price. All Ranibizumab biosimilars that have gained approval were tested in double masked Phase 3 clinical studies. The use of Ranibizumab biosimilars in neovascular AMD is well reported in the bibliography. Nevertheless, over the last few years, there is a tendency of using biosimilars in other retinal diseases like retinopathy of prematurity (ROP), diabetic macular edema (DME) or polypoidal choroidal vasculopathy (PCV). In conclusion, ranibizumab biosimilars offer a promising avenue for the management of retinal diseases, especially in countries with lower socioeconomic status, where there is lack of availability of innovator ranibizumab. However, further research is required to fully explore their efficacy, safety, and long-term outcomes in a plethora of retinal diseases.},
}
@article {pmid38347098,
year = {2024},
author = {Chen, R and Zhang, W and Song, F and Yu, H and Cao, D and Zheng, Y and He, M and Shi, D},
title = {Translating color fundus photography to indocyanine green angiography using deep-learning for age-related macular degeneration screening.},
journal = {NPJ digital medicine},
volume = {7},
number = {1},
pages = {34},
pmid = {38347098},
issn = {2398-6352},
abstract = {Age-related macular degeneration (AMD) is the leading cause of central vision impairment among the elderly. Effective and accurate AMD screening tools are urgently needed. Indocyanine green angiography (ICGA) is a well-established technique for detecting chorioretinal diseases, but its invasive nature and potential risks impede its routine clinical application. Here, we innovatively developed a deep-learning model capable of generating realistic ICGA images from color fundus photography (CF) using generative adversarial networks (GANs) and evaluated its performance in AMD classification. The model was developed with 99,002 CF-ICGA pairs from a tertiary center. The quality of the generated ICGA images underwent objective evaluation using mean absolute error (MAE), peak signal-to-noise ratio (PSNR), structural similarity measures (SSIM), etc., and subjective evaluation by two experienced ophthalmologists. The model generated realistic early, mid and late-phase ICGA images, with SSIM spanned from 0.57 to 0.65. The subjective quality scores ranged from 1.46 to 2.74 on the five-point scale (1 refers to the real ICGA image quality, Kappa 0.79-0.84). Moreover, we assessed the application of translated ICGA images in AMD screening on an external dataset (n = 13887) by calculating area under the ROC curve (AUC) in classifying AMD. Combining generated ICGA with real CF images improved the accuracy of AMD classification with AUC increased from 0.93 to 0.97 (P < 0.001). These results suggested that CF-to-ICGA translation can serve as a cross-modal data augmentation method to address the data hunger often encountered in deep-learning research, and as a promising add-on for population-based AMD screening. Real-world validation is warranted before clinical usage.},
}
@article {pmid38345159,
year = {2024},
author = {Mathieu, A and Ajana, S and Korobelnik, JF and Le Goff, M and Gontier, B and Rougier, MB and Delcourt, C and Delyfer, MN},
title = {DeepAlienorNet: A deep learning model to extract clinical features from colour fundus photography in age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {5},
pages = {e823-e830},
doi = {10.1111/aos.16660},
pmid = {38345159},
issn = {1755-3768},
support = {PHRC 2012//Minist&#xe8;re de la Sant&#xe9;/ ; PHRC12_157 ECLAIR//Minist&#xe8;re de la Sant&#xe9;/ ; ANR 2010-PRSP-011 VISA//Agence Nationale de la Recherche/ ; //CFSR Recherche (Club Francophone des Sp&#xe9;cialistes de la R&#xe9;tine)/ ; //University of Bordeaux/ ; //Fondation Voir et Entendre/ ; //Th&#xe9;a Pharma/ ; //CNSA (Caisse Nationale pour la Solidarit&#xe9; et l'Autonomie)/ ; },
mesh = {Humans ; *Deep Learning ; Aged ; Male ; Female ; *Photography/methods ; *Fundus Oculi ; Macular Degeneration/diagnosis ; Retinal Drusen/diagnosis ; Aged, 80 and over ; ROC Curve ; },
abstract = {OBJECTIVE: This study aimed to develop a deep learning (DL) model, named 'DeepAlienorNet', to automatically extract clinical signs of age-related macular degeneration (AMD) from colour fundus photography (CFP).<br><br>METHODS AND ANALYSIS: The ALIENOR Study is a cohort of French individuals 77&#x2009;years of age or older. A multi-label DL model was developed to grade the presence of 7 clinical signs: large soft drusen (>125&#x2009;&#x3bc;m), intermediate soft (63-125&#x2009;&#x3bc;m), large area of soft drusen (total area >500&#x2009;&#x3bc;m), presence of central soft drusen (large or intermediate), hyperpigmentation, hypopigmentation, and advanced AMD (defined as neovascular or atrophic AMD). Prediction performances were evaluated using cross-validation and the expert human interpretation of the clinical signs as the ground truth.<br><br>RESULTS: A total of 1178 images were included in the study. Averaging the 7 clinical signs' detection performances, DeepAlienorNet achieved an overall sensitivity, specificity, and AUROC of 0.77, 0.83, and 0.87, respectively. The model demonstrated particularly strong performance in predicting advanced AMD and large areas of soft drusen. It can also generate heatmaps, highlighting the relevant image areas for interpretation.<br><br>CONCLUSION: DeepAlienorNet demonstrates promising performance in automatically identifying clinical signs of AMD from CFP, offering several notable advantages. Its high interpretability reduces the black box effect, addressing ethical concerns. Additionally, the model can be easily integrated to automate well-established and validated AMD progression scores, and the user-friendly interface further enhances its usability. The main value of DeepAlienorNet lies in its ability to assist in precise severity scoring for further adapted AMD management, all while preserving interpretability.},
}
@article {pmid38344832,
year = {2024},
author = {Shen, J and Chen, L and Lv, X and Liu, N and Miao, Y and Zhang, Q and Xiao, Z and Li, M and Yang, Y and Liu, Z and Chen, Q},
title = {Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {36},
number = {23},
pages = {e2314095},
doi = {10.1002/adma.202314095},
pmid = {38344832},
issn = {1521-4095},
support = {2020YFA0211100//National Research Programs of China/ ; 2022YFA1206500//National Research Programs of China/ ; 52250002//National Natural Science Foundation of China/ ; 52325106//National Natural Science Foundation of China/ ; 52271248//National Natural Science Foundation of China/ ; //Collaborative Innovation Center of Suzhou Nano Science and Technology/ ; //Suzhou Key Laboratory of Nanotechnology and Biomedicine/ ; //111 Program from the Ministry of Education of China/ ; },
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; *Nanoparticles/chemistry ; Rabbits ; *Delayed-Action Preparations/chemistry ; Mice ; *Indoles/chemistry/therapeutic use ; Angiogenesis Inhibitors/chemistry/pharmacology/therapeutic use ; Drug Liberation ; Humans ; Drug Carriers/chemistry ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis reduce inflammation and counteract oxidative stress and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.},
}
@article {pmid38295996,
year = {2024},
author = {Appell, MB and Pejavar, J and Pasupathy, A and Rompicharla, SVK and Abbasi, S and Malmberg, K and Kolodziejski, P and Ensign, LM},
title = {Next generation therapeutics for retinal neurodegenerative diseases.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {367},
number = {},
pages = {708-736},
pmid = {38295996},
issn = {1873-4995},
support = {R01 EY031041/EY/NEI NIH HHS/United States ; R01 EY033386/EY/NEI NIH HHS/United States ; T32 EY007143/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Drug Delivery Systems ; *Neurodegenerative Diseases/drug therapy ; *Macular Degeneration/drug therapy ; Pharmaceutical Preparations ; Administration, Topical ; },
abstract = {Neurodegenerative diseases affecting the visual system encompass glaucoma, macular degeneration, retinopathies, and inherited genetic disorders such as retinitis pigmentosa. These ocular pathologies pose a serious burden of visual impairment and blindness worldwide. Current treatment modalities include small molecule drugs, biologics, or gene therapies, most of which are administered topically as eye drops or as injectables. However, the topical route of administration faces challenges in effectively reaching the posterior segment and achieving desired concentrations at the target site, while injections and implants risk severe complications, such as retinal detachment and endophthalmitis. This necessitates the development of innovative therapeutic strategies that can prolong drug release, deliver effective concentrations to the back of the eye with minimal systemic exposure, and improve patient compliance and safety. In this review, we introduce retinal degenerative diseases, followed by a discussion of the existing clinical standard of care. We then delve into detail about drug and gene delivery systems currently in preclinical and clinical development, including formulation and delivery advantages/drawbacks, with a special emphasis on potential for clinical translation.},
}
@article {pmid38341583,
year = {2024},
author = {Liu, P and Sun, D and Zhang, S and Chen, S and Wang, X and Li, H and Wei, F},
title = {PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies.},
journal = {Cell &amp; bioscience},
volume = {14},
number = {1},
pages = {21},
pmid = {38341583},
issn = {2045-3701},
support = {Grant No.81970812//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis.<br><br>MAIN BODY: In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease.<br><br>CONCLUSION: Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.},
}
@article {pmid38341189,
year = {2024},
author = {Dervenis, N and Dervenis, P and Agorogiannis, E},
title = {Neovascular age-related macular degeneration: disease pathogenesis and current state of molecular biomarkers predicting treatment response-a scoping review.},
journal = {BMJ open ophthalmology},
volume = {9},
number = {1},
pages = {},
pmid = {38341189},
issn = {2397-3269},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factors/therapeutic use ; Neovascularization, Pathologic/drug therapy ; *Macular Degeneration/diagnosis ; },
abstract = {Age-related macular degeneration is a major cause of blindness, and the development of anti-vascular endothelial growth factor (VEGF) intravitreal treatments has revolutionised the management of the disease. At the same time, new challenges and unmet needs arose due to the limitations of the current therapeutic options. Neovascularisation development during the course of the disease has a complex pathogenetic mechanism, and several biomarkers and their association with treatment outcomes have been investigated. We reviewed the relevant literature about neovascularisation development and biomarkers related to response to treatment. Improving our knowledge on the field can improve patient outcomes and offer personalised care.},
}
@article {pmid38338978,
year = {2024},
author = {Salman, A and McClements, ME and MacLaren, RE},
title = {CRISPR Manipulation of Age-Related Macular Degeneration Haplotypes in the Complement System: Potential Future Therapeutic Applications/Avenues.},
journal = {International journal of molecular sciences},
volume = {25},
number = {3},
pages = {},
pmid = {38338978},
issn = {1422-0067},
mesh = {Humans ; Aged ; Haplotypes ; *Complement Factor B ; *Macular Degeneration/genetics/therapy/pathology ; Complement Activation/genetics ; Risk Factors ; Polymorphism, Single Nucleotide ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different complement genes representing an increased risk factor. With several complement inhibitors explored in clinical trials showing limited success, patients with AMD are still without a reliable treatment option. This indicates that there is still a gap of knowledge in the functional implications and manipulation of the complement system in AMD, hindering the progress towards translational treatments. Since the discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool, the field of molecular biology has been revolutionised. Genetic variants in the complement system have long been associated with an increased risk of AMD, and a variety of haplotypes have been identified to be predisposing/protective, with variation in complement genes believed to be the trigger for dysregulation of the cascade leading to inflammation. AMD-haplotypes (SNPs) alter specific aspects of the activation and regulation of the complement cascade, providing valuable insights into the pathogenic mechanisms of AMD with important diagnostic and therapeutic implications. The effect of targeting these AMD-related SNPs on the regulation of the complement cascade has been poorly explored, and the CRISPR/Cas system provides an ideal tool with which to explore this avenue. Current research concentrates on the association events of specific AMD-related SNPs in complement genes without looking into the effect of targeting these SNPs and therefore influencing the complement system in AMD pathogenesis. This review will explore the current understanding of manipulating the complement system in AMD pathogenesis utilising the genomic manipulation powers of the CRISPR/Cas systems. A number of AMD-related SNPs in different complement factor genes will be explored, with a particular emphasis on factor H (CFH), factor B (CFB), and complement C3 (C3).},
}
@article {pmid38338904,
year = {2024},
author = {Qu, S and Lin, H and Pfeiffer, N and Grus, FH},
title = {Age-Related Macular Degeneration and Mitochondria-Associated Autoantibodies: A Review of the Specific Pathogenesis and Therapeutic Strategies.},
journal = {International journal of molecular sciences},
volume = {25},
number = {3},
pages = {},
pmid = {38338904},
issn = {1422-0067},
support = {202108080132//China Scholarship Council/ ; },
mesh = {Humans ; Aged ; *Macular Degeneration/therapy/genetics ; Mitochondria/pathology ; Retina/pathology ; *Retinal Diseases/metabolism ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a severe retinal disease that causes irreversible visual loss and blindness in elderly populations worldwide. The pathological mechanism of AMD is complex, involving the interactions of multiple environmental and genetic factors. A poor understanding of the disease leads to limited treatment options and few effective prevention methods. The discovery of autoantibodies in AMD patients provides an opportunity to explore the pathogenesis and treatment direction of the disease. This review focuses on the mitochondria-associated autoantibodies and summarizes the functional roles of mitochondria under physiological conditions and their alterations during the pathological states. Additionally, it discusses the crosstalk between mitochondria and other organelles, as well as the mitochondria-related therapeutic strategies in AMD.},
}
@article {pmid38338894,
year = {2024},
author = {Romero, FJ and Diaz-Llopis, M and Romero-Gomez, MI and Miranda, M and Romero-Wenz, R and Sancho-Pelluz, J and Romero, B and Muriach, M and Barcia, JM},
title = {Small Extracellular Vesicles and Oxidative Pathophysiological Mechanisms in Retinal Degenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {25},
number = {3},
pages = {},
pmid = {38338894},
issn = {1422-0067},
support = {PID2020-117875GB-I00/AEI/ 10.13039/501100011033//Agencia Estatal de Investigaci&#xf3;n/ ; PI21/00083//Instituto de Salud Carlos III/ ; 'Proyectos Puente y en Consolidaci&#xf3;n'&#xa0;CEU FUSP 2022-2023//Fundacion San Pablo CEU/ ; },
mesh = {Humans ; Retina/metabolism ; *Retinal Degeneration/metabolism ; *Extracellular Vesicles/metabolism ; *MicroRNAs/genetics/metabolism ; Oxidative Stress ; },
abstract = {This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles' cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.},
}
@article {pmid38337561,
year = {2024},
author = {Kim, JG and Kim, YC and Kang, KT},
title = {Two-Year Follow-Up Study of Patients with Neovascular Age-Related Macular Degeneration Undergoing Anti-VEGF Treatment during the COVID-19 Pandemic.},
journal = {Journal of clinical medicine},
volume = {13},
number = {3},
pages = {},
pmid = {38337561},
issn = {2077-0383},
support = {BISA Research Grant of Keimyung University in 2022//BISA Research Grant of Keimyung University in 2022/ ; },
abstract = {BACKGROUND: regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate disease progression.<br><br>METHODS: we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic.<br><br>RESULTS: The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 &#xb1; 1.51 months (p = 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (p < 0.001). The delayed group showed greater mean BCVA deterioration (p = 0.027) and central subfield thickness (p = 0.037) at 6 months and worse maximum subretinal fluid height (p = 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year.<br><br>CONCLUSION: the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals.},
}
@article {pmid38335626,
year = {2024},
author = {Françon, A and Behar-Cohen, F and Torriglia, A},
title = {The blue light hazard and its use on the evaluation of photochemical risk for domestic lighting. An in vivo study.},
journal = {Environment international},
volume = {184},
number = {},
pages = {108471},
doi = {10.1016/j.envint.2024.108471},
pmid = {38335626},
issn = {1873-6750},
mesh = {Animals ; Rats ; *Blue Light/adverse effects ; *Lighting/adverse effects ; Retina ; },
abstract = {BACKGROUND: Nowadays artificial light highly increases human exposure to light leading to circadian rhythm and sleep perturbations. Moreover, excessive exposure of ocular structures to photons can induce irreversible retinal damage. Meta-analyses showed that sunlight exposure influences the age of onset and the progression of Age-related macular degeneration (AMD), the leading cause of blindness in people over fifty-year old. Currently, the blue-light hazard (BLH) curve is used in the evaluation of the phototoxicity of a light source for domestic lighting regulations.<br><br>OBJECTIVES: Here, we analyze the phototoxicity threshold in rats and investigate the role played by the light spectrum, assessing the relevance of the use of the BLH-weighting to define phototoxicity.<br><br>METHODS: We exposed albino rats to increasing doses of blue and white light, or to lights of different colors to evaluate the impact of each component of the white light spectrum on phototoxicity. Cellular mechanisms of cell death and cellular stress induced by light were analyzed.<br><br>RESULTS: Our results show that the phototoxicity threshold currently accepted for rats is overestimated by a factor of 50 when considering blue light and by a factor of 550 concerning white light. This is the result of the toxicity induced by green light that increases white light toxicity by promoting an inflammatory response. The content of green in white light induces 8 fold more invasion of macrophages in the retina than the content of blue light. Moreover, the use of BLH-weighting does not evaluate the amount of red radiations contained in white light that mitigates damage by inhibiting the nuclear translocation of L-DNase II and reducing by 33% the number of TUNEL-positive cells.<br><br>DISCUSSION: These findings question the current methods to determine the phototoxicity of a light source and show the necessity to take into account the entire emission spectrum. As current human phototoxicity thresholds were estimated with the same methods used for rats, our results suggest that they might need to be reconsidered.},
}
@article {pmid38335542,
year = {2024},
author = {Prabha, AJ and Venkatesan, C and Fathimal, MS and Nithiyanantham, KK and Kirubha, SPA},
title = {RD-OCT net: hybrid learning system for automated diagnosis of macular diseases from OCT retinal images.},
journal = {Biomedical physics &amp; engineering express},
volume = {10},
number = {2},
pages = {},
doi = {10.1088/2057-1976/ad27ea},
pmid = {38335542},
issn = {2057-1976},
mesh = {Humans ; *Macular Edema/diagnostic imaging/complications ; *Diabetic Retinopathy/diagnostic imaging/complications ; Artificial Intelligence ; Tomography, Optical Coherence/adverse effects/methods ; *Retinal Diseases/diagnostic imaging/complications ; },
abstract = {Macular Edema is a leading cause of visual impairment and blindness in patients with ocular fundus diseases. Due to its non-invasive and high-resolution characteristics, optical coherence tomography (OCT) has been extensively utilized for the diagnosis of macular diseases. The manual detection of retinal diseases by clinicians is a laborious process, further complicated by the challenging identification of macular diseases. This difficulty arises from the significant pathological alterations occurring within the retinal layers, as well as the accumulation of fluid in the retina. Deep Learning neural networks are utilized for automatic detection of retinal diseases. This paper aims to propose a lightweight hybrid learning Retinal Disease OCT Net with a reduced number of trainable parameters and enable automatic classification of retinal diseases. A Hybrid Learning Retinal Disease OCT Net (RD-OCT) is utilized for the multiclass classification of major retinal diseases, namely neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and normal retinal conditions. The diagnosis of retinal diseases is facilitated by the use of hybrid learning models and pre-trained deep learning models in the field of artificial intelligence. The Hybrid Learning RD-OCT Net provides better accuracy of 97.6% for nAMD, 98.08% for DME, 98% for RVO, and 97% for the Normal group. The respective area under the curve values were 0.99, 0.97, 1.0, and 0.99. The utilization of the RD-OCT model will be useful for ophthalmologists in the diagnosis of prevalent retinal diseases, due to the simplicity of the system and reduced number of trainable parameters.},
}
@article {pmid38334879,
year = {2024},
author = {Zaher, S and Rodriguez-Villalobos, H},
title = {Triple Gram-negative bacterial endophthalmitis following intravitreal injection.},
journal = {Journal of ophthalmic inflammation and infection},
volume = {14},
number = {1},
pages = {9},
pmid = {38334879},
issn = {1869-5760},
abstract = {PURPOSE: To describe a puzzling case of endophthalmitis caused by three unusual bacteria after intravitreal injection, its outcome, and underlying questions.<br><br>FINDINGS: A 70-year-old female patient was diagnosed with acute endophthalmitis following intravitreal aflibercept injection for age-related macular degeneration. A standard tap and inject procedure was performed. Microbiological analyses on the anterior chamber and vitreous samples yielded the presence of three non-fermenting Gram-negative rods: Pseudomonas stutzeri, Stenotrophomonas maltophilia, and Ochrobactrum anthropi. The outcome was favorable after intravitreal injections of vancomycin and ceftazidime, with an almost complete recovery of the visual acuity to its baseline level. No potential source of infection was identified.<br><br>CONCLUSION: Endophthalmitis following intravitreal injection can be caused by a wide variety of bacteria, including some rare Gram-negative species. They can sometimes co-exist in a single patient, but their virulence may vary greatly. Due to the variable antibiotic susceptibility and frequent multiresistance associated with non-fermenting Gram-negative rods, a prompt microbiological approach is required. Favorable outcome can be achieved with standard management.},
}
@article {pmid38334303,
year = {2024},
author = {Restrepo, D and Quion, JM and Do Carmo Novaes, F and Azevedo Costa, ID and Vasquez, C and Bautista, AN and Quiminiano, E and Lim, PA and Mwavu, R and Celi, LA and Nakayama, LF},
title = {Ophthalmology Optical Coherence Tomography Databases for Artificial Intelligence Algorithm: A Review.},
journal = {Seminars in ophthalmology},
volume = {39},
number = {3},
pages = {193-200},
doi = {10.1080/08820538.2024.2308248},
pmid = {38334303},
issn = {1744-5205},
mesh = {Humans ; *Artificial Intelligence ; *Ophthalmology/methods ; Tomography, Optical Coherence/methods ; Algorithms ; Retina/pathology ; },
abstract = {BACKGROUND: Imaging plays a pivotal role in eye assessment. With the introduction of advanced machine learning and artificial intelligence (AI), the focus has shifted to imaging datasets in ophthalmology. While disparities and health inequalities hidden within data are well-documented, the ophthalmology field faces specific challenges to the creation and maintenance of datasets. Optical Coherence Tomography (OCT) is useful for the diagnosis and monitoring of retinal pathologies, making it valuable for AI applications. This review aims to identify and compare the landscape of publicly available optical coherence tomography databases for AI applications.<br><br>METHODS: We conducted a literature review on OCT and AI articles with publicly accessible datasets, using PubMed, Scopus, and Web of Science databases. The review retrieved 183 articles, and after full-text analysis, 50 articles were included. From the included articles were identified 8 publicly available OCT datasets, focusing on patient demographics and clinical details for thorough assessment and comparison.<br><br>RESULTS: The resulting datasets encompass 154,313 images collected from Spectralis, Cirrus HD, Topcon 3D, and Bioptigen devices. These datasets included normal exams, age-related macular degeneration, and diabetic maculopathy, among others. Comprehensive demographic information is available in one dataset and the USA is the most represented population.<br><br>DISCUSSION: Current publicly available OCT databases for AI applications exhibit limitations, stemming from their non-representative nature and the lack of comprehensive demographic information. Limited datasets hamper research and equitable AI development. To promote equitable AI algorithmic development in ophthalmology, there is a need for the creation and dissemination of more representative datasets.},
}
@article {pmid38333749,
year = {2024},
author = {Mousavi, M and Mousavi, A and Jamei, B and Sameni, H and Zarbakhsh, S and Aboutaleb Kadkhodaeian, H},
title = {Classification, location, and intensity of granules in retinal pigment epithelium following sodium iodate injection in rat animal model.},
journal = {Iranian journal of basic medical sciences},
volume = {27},
number = {3},
pages = {286-296},
pmid = {38333749},
issn = {2008-3866},
abstract = {OBJECTIVES: Age-related macular degeneration (AMD) is one of the eye diseases that can affect a person's central vision. Retinal pigment epithelium (RPE) cells are damaged in this medical condition and some pigments are presented in these cells. Here, we aimed to investigate melanin and lipofuscin granules of RPE cells as a precursor of AMD.<br><br>MATERIALS AND METHODS: Hooded rats (n=18) were divided into two groups and received 100 &#x3bc;l of sodium iodate (SI) into the retro-orbital sinus of their eyes at 40 and 60 mg/kg doses. The total number of melanin and lipofuscin granules, different types of granules, cytoplasmic dispersion of granules as well as morphological changes in the shape and number of nuclei of RPE cells were evaluated over the course of 1-30 days.<br><br>RESULTS: The total number of melanin pigments increases over time at a dose of 40 mg/kg and decreases at a dose of 60 mg/kg. Also, the total number of lipofuscin granules in 40 mg/kg increases over time and decreases in 60 mg/kg. Autofluorescent intensity (AF) is also increased at 40 mg/kg, but at 60 mg/kg, the highest intensity is on day 7. Also, the highest number of multinucleated giant cells was on day 7 at 60 mg/kg and the most changes in cell appearance due to sodium iodate injection were seen on the first day after injection.<br><br>CONCLUSION: We demonstrated that granules and autofluorescent intensity appear to decrease at high doses of sodium iodate, which is similar to the advanced stage of the AMD disease, where the number of granules and AF intensity increase in the middle and even early stages of the disease.},
}
@article {pmid38333436,
year = {2024},
author = {Sannan, NS and Elsayid, M and Alsharif, G and Ramadan, M and Alhalwani, AY and Qahwaji, RM and Arbaeen, A and Aalam, WA and Alqahtani, AS and Talat, K},
title = {Correlation Between C-Reactive Protein and Lipid Analytes in Dry Age-Related Macular Degeneration: A Retrospective Study.},
journal = {Cureus},
volume = {16},
number = {1},
pages = {e51935},
pmid = {38333436},
issn = {2168-8184},
abstract = {INTRODUCTION: To date few studies have investigated the correlation between inflammatory markers and lipoproteins in the serum of age-related macular degeneration (AMD) patients, often reporting conflicting findings. This study aimed to investigate the correlation between lipid analytes and C-reactive protein (CRP) levels in individuals diagnosed with dry AMD.<br><br>METHODS: A standard clinical lipid panel (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoproteins) and CRP laboratory results were retrospectively collected from the medical records of patients with dry AMD and age- and sex-matched controls.<br><br>RESULTS: The study included 90 patients with dry AMD and 270 patients without AMD. In univariate analysis, CRP showed a higher mean value in cases than in controls. After adjusting for age and sex, CRP and triglyceride levels showed significant differences between cases and controls. Pearson's correlation analysis revealed a significant negative correlation between CRP and HDL levels in the dry AMD group (n=90). Other lipid analytes showed no significant correlations with CRP.<br><br>CONCLUSION: Our findings add to the growing body of evidence linking inflammation to AMD. Although it is unclear whether changes in serum CRP and triglyceride levels are the causes or effects, monitoring both analytes may be beneficial as an early disease predictor, especially in individuals with a family history of AMD. The negative correlation between CRP and HDL (i.e., inflammation and good cholesterol) may be targeted for future therapies.},
}
@article {pmid38333302,
year = {2024},
author = {Almaliotis, D and Almpanidou, S and Chatzimbalis, T and Nikolaidou, A and Talimtzi, P and Karampatakis, V},
title = {Correlation between color vision, visual acuity, contrast sensitivity and photostress recovery in the visually impaired: a cross-sectional study.},
journal = {Annals of medicine and surgery (2012)},
volume = {86},
number = {2},
pages = {742-747},
pmid = {38333302},
issn = {2049-0801},
abstract = {BACKGROUND: To investigate the correlation of colour vision, visual acuity, contrast sensitivity, and photostress recovery time test scores in visually impaired patients.<br><br>MATERIALS AND METHODS: A total of 133 subjects were enroled and 133 eyes were examined. The pathological group consisted of 76 (57.1%) males with an average age of 68.0 (SD=13.2) and 57 (42.9%) females, with an average age of 68.1 (SD=15.2), Mann-Whitney U test was used to evaluate the differences in K-colour tests, HRR, visual acuity, Contrast Sensitivity test and photostress recovery time test between two different groups of severity.<br><br>RESULTS: Correlations were found among colour vision tests, visual acuity, contrast sensitivity, and photostress recovery time scores in eyes with age-related macular degeneration, with diabetic retinopathy, with optic nerve diseases, and various other retinal diseases (P<0.05). In patients with moderate-visual impairments.<br><br>CONCLUSIONS: The colour vision test scores correlate with the scores of visual acuity, contrast sensitivity, and photostess recovery time test. It may be a useful clinical surrogate for functional vision.},
}
@article {pmid38333011,
year = {2024},
author = {Yu, Y and Liu, Y and Meng, Z},
title = {Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota's influence.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1356324},
pmid = {38333011},
issn = {1663-9812},
abstract = {The pathogenesis of age-related macular degeneration (AMD), a degenerative retinopathy, remains unclear. Administration of anti-vascular endothelial growth factor agents, antioxidants, fundus lasers, photodynamic therapy, and transpupillary warming has proven effective in alleviating symptoms; however, these interventions cannot prevent or reverse AMD. Increasing evidence suggests that AMD risk is linked to changes in the composition, abundance, and diversity of the gut microbiota (GM). Activation of multiple signaling pathways by GM metabolites, including lipopolysaccharides, oxysterols, short-chain fatty acids (SCFAs), and bile acids (BAs), influences retinal physiology. Traditional Chinese medicine (TCM), known for its multi-component and multi-target advantages, can help treat AMD by altering GM composition and regulating the levels of certain substances, such as lipopolysaccharides, reducing oxysterols, and increasing SCFA and BA contents. This review explores the correlation between GM and AMD and interventions for the two to provide new perspectives on treating AMD with TCM.},
}
@article {pmid38332904,
year = {2024},
author = {Regillo, CD and Nijm, LM and Shechtman, DL and Kaiser, PK and Karpecki, PM and Ryan, EH and Ip, MS and Yeu, E and Kim, T and Rafieetary, MR and Donnenfeld, ED},
title = {Considerations for the Identification and Management of Geographic Atrophy: Recommendations from an Expert Panel.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {325-335},
pmid = {38332904},
issn = {1177-5467},
abstract = {Newly approved treatments for patients with geographic atrophy are changing the treatment paradigm, highlighting the need for eye care providers (ECPs) to have a set of recommendations on how to best manage GA patients. Here, we outline how to identify various stages of age-related macular degeneration including geographic atrophy (GA) by examining optimal management scenarios implicating various ECPs and reviewing treatment considerations for patients with GA. Early identification of GA will lead to optimal patient outcomes, while a standardized management scenario will reduce clinical burden among ECPs treating patients with GA.},
}
@article {pmid38331775,
year = {2024},
author = {Terheyden, JH and Fink, DJ and Mercieca, K and Wintergerst, MWM and Holz, FG and Finger, RP},
title = {Knowledge about age-related eye diseases in the general population in Germany.},
journal = {BMC public health},
volume = {24},
number = {1},
pages = {409},
pmid = {38331775},
issn = {1471-2458},
mesh = {Adult ; Humans ; *Cataract/epidemiology ; Cross-Sectional Studies ; *Diabetes Mellitus ; *Eye Diseases/epidemiology ; *Glaucoma/epidemiology/complications ; *Macular Degeneration/epidemiology ; Surveys and Questionnaires ; Male ; Female ; },
abstract = {BACKGROUND: With a rising prevalence of age-related eye diseases, prevention and early diagnosis of these conditions are key goals of public eye health. Disease-related knowledge in the general public supports these goals but there is little data available. Thus, we have assessed knowledge of cataract, glaucoma, age-related macular degeneration (AMD) and diabetic eye disease in the German adult general population in a cross-sectional study and identified target groups for health education interventions.<br><br>METHODS: Knowledge assessment content was identified based on a literature review, expert input, and a list of items was generated after a qualitative selection process. The resulting 16-item instrument (4 items per condition) was administered to 1,008 participants from a survey panel, demographically representative of the adult German population. Test properties were evaluated based on a Rasch model and multiple correspondence analysis (MCA). Binary-logistic regression analysis was performed to investigate associations with age, sex, education level, employment status, marital status, income, reported health status, visual difficulties, and recent general practitioner (GP) and ophthalmologist consultations.<br><br>RESULTS: Replies were correct for a median of 9 out of 16 (range 2 - 16) items, which differed between conditions (p&#x2009;<&#x2009;0.0001). Most responses were correct for cataract items (median: 3 / 4) and least were correct for AMD items (median: 2 / 4). 27%, 9%, 1% and 19% of respondents replied correctly to all cataract, glaucoma, AMD and diabetic eye disease-related items, respectively. Rasch analysis suggested an adequate targeting of items and in MCA, no evidence of multidimensionality was present. Older age, being retired, decreased general health and recent GP or ophthalmology consultations were significantly associated with more knowledge about common eye conditions (p&#x2009;&#x2264;&#x2009;0.005). GP or ophthalmology consultations remained significant in a multivariable model (p&#x2009;&#x2264;&#x2009;0.011).<br><br>CONCLUSIONS: Knowledge gaps regarding eye health are considerable in the German general population and should therefore be addressed in educational interventions targeting the public. Special attention when designing such campaigns needs to be paid to infrequent users of the healthcare system. Knowledge of AMD seems to be poorer compared to other eye conditions.},
}
@article {pmid38331017,
year = {2024},
author = {Hui, Q and Yang, N and Xiong, C and Zhou, S and Zhou, X and Jin, Q and Xu, X},
title = {Isorhamnetin suppresses the epithelial-mesenchymal transition of the retinal pigment epithelium both in vivo and in vitro through Nrf2-dependent AKT/GSK-3β pathway.},
journal = {Experimental eye research},
volume = {240},
number = {},
pages = {109823},
doi = {10.1016/j.exer.2024.109823},
pmid = {38331017},
issn = {1096-0007},
mesh = {Humans ; Mice ; Animals ; Aged ; *Proto-Oncogene Proteins c-akt/metabolism ; *Signal Transduction ; Glycogen Synthase Kinase 3 beta/metabolism ; NF-E2-Related Factor 2/metabolism ; Retinal Pigment Epithelium/metabolism ; Mice, Inbred C57BL ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Quercetin/*analogs &amp; derivatives ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of blindness in the elderly worldwide. Multiple studies have shown that epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of AMD. Isorhamnetin (Isor) is a flavonoid compound that inhibits EMT in tumor cells. However, whether it can also attenuate EMT in the retinal pigment epithelium (RPE) is unknown. Therefore, our study was designed to probe the possible impact of Isor on EMT process in both mouse retina and ARPE-19 cells. C57BL/6 mice were utilized to establish a dry AMD model. Isor and LCZ (a mixture of luteine/β-carotene/zinc gluconate) were administered orally for 3 months. The effects of Isor on the retina were evaluated using fundus autofluorescence, optical coherence tomography, and transmission electron microscopy. Transwell and wound healing assay were employed to assess ARPE-19 cell migration. Western blotting and immunofluorescence were used to measure the protein expressions associated with EMT, Nrf2 and AKT/GSK-3β pathway. The findings indicated that Isor alleviated dry AMD-like pathological changes in vehicle mice retina, inhibited the migration of Ox-LDL-treated ARPE-19 cells, and repressed the EMT processes in vivo and in vitro. Furthermore, Isor activated Nrf2 pathway and deactivated AKT/GSK-3β pathway in both vehicle mice and ARPE-19 cells. Interestingly, when Nrf2 siRNA was transfected into ARPE-19 cells, the inhibitory effect of Isor on EMT and AKT/GSK-3β pathway was attenuated. These results suggested that Isor inhibited EMT processes via Nrf2-dependent AKT/GSK-3β pathway and is a promising candidate for dry AMD treatment.},
}
@article {pmid38330506,
year = {2024},
author = {Papaioannou, C},
title = {Advancements in the treatment of age-related macular degeneration: a comprehensive review.},
journal = {Postgraduate medical journal},
volume = {100},
number = {1185},
pages = {445-450},
doi = {10.1093/postmj/qgae016},
pmid = {38330506},
issn = {1469-0756},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/therapy/diagnosis/drug therapy ; Genetic Therapy/methods ; Ranibizumab/therapeutic use ; Risk Factors ; Wet Macular Degeneration/therapy/diagnosis/drug therapy ; Artificial Intelligence ; },
abstract = {Age-related macular degeneration (AMD) stands as a leading cause of irreversible blindness, particularly affecting central vision and impeding daily tasks. This paper provides a thorough exploration of AMD, distinguishing between its two main subtypes-Wet and Dry AMD-while shedding light on the prevalence and risk factors, including age, genetics, and smoking. The focus shifts to the current and future treatment landscape, examining both Dry and Wet AMD. Regarding Dry AMD, interventions such as antioxidant supplementation and ongoing clinical trials offer hope. Notable among these is Pegcetacoplan which is the only Food and Drug Administration (FDA)-approved medication, displaying promising results in reducing geographic atrophy lesions. For Wet AMD, anti-Vascular Endothelial Growth Factor therapies like Ranibizumab (Lucentis®) have been instrumental, and newer drugs like Faricimab and OPT-302 show comparable efficacy with extended dosing intervals. Additionally, gene therapies such as RGX-314 present a potential paradigm shift, reducing or eliminating the need for frequent injections. Biosimilars offer cost-effective alternatives. The paper also delves into the integration of technology and artificial intelligence in AMD management, highlighting the role of smartphone apps for patient monitoring and artificial intelligence algorithms for diagnosis and surveillance. Furthermore, patient perspectives on artificial intelligence demonstrate a positive correlation between understanding and trust. The narrative concludes with a glimpse into ground-breaking technologies, including retinal implants and bionic chips, offering hope for vision restoration. Overall, this paper underscores the multifaceted approach in addressing AMD, combining traditional and innovative strategies, paving the way for a more promising future in AMD treatment.},
}
@article {pmid38329693,
year = {2025},
author = {Cho, WKT and Hwang, DG},
title = {Sociodemographic Disparities in Preoperative Visual Acuity and Cataract Surgery Utilization in the San Francisco Bay Area.},
journal = {Journal of racial and ethnic health disparities},
volume = {12},
number = {2},
pages = {740-753},
pmid = {38329693},
issn = {2196-8837},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Cataract Extraction/statistics &amp; numerical data ; Cross-Sectional Studies ; Ethnicity/statistics &amp; numerical data ; *Healthcare Disparities/ethnology/statistics &amp; numerical data ; Retrospective Studies ; San Francisco/epidemiology ; Sociodemographic Factors ; *Visual Acuity ; Racial Groups ; },
abstract = {OBJECTIVE: We examined whether cataract surgery utilization and preoperative visual acuity were associated with patient-specific factors, including ocular findings and comorbidities, general biomedical factors, and/or sociodemographic factors.<br><br>DESIGN: Retrospective, cross-sectional study.<br><br>We reviewed the electronic health records of patients from 2012 to 2022 who were examined and followed for at least 2&#xa0;years by an eye care provider at University of California San Francisco Health (UCSF Health)&#xa0;and who had cataract in at least one eye associated with best-corrected visual acuity of 20/25 or worse. Data include ocular factors (e.g., best-corrected visual acuity, lens opacity grade, diagnoses of glaucoma, and/or age-related macular degeneration), biomedical comorbidities, and sociodemographic factors including race/ethnicity, health insurance coverage, primary language spoken, and social vulnerability index.<br><br>METHODS: Logistic and multivariate regression analyses.<br><br>MAIN OUTCOME MEASURES: We examined cataract surgery utilization and preoperative best-corrected visual acuity.<br><br>RESULTS: Compared to White and Asian patients, Black patients had the lowest rates of cataract surgery utilization and the poorest mean preoperative visual acuities, with Hispanic patients following in second place in both categories. However, when the analysis controlled for sociodemographic and biomedical factors, Medicaid insurance and speaking Chinese as a primary language emerged as significant associations. In addition, higher cataract surgery utilization rates were associated with worse preoperative best-corrected visual acuity, a concurrent diagnosis of glaucoma, and a concurrent diagnosis of macular degeneration. Worse preoperative visual acuity was associated with Spanish or Chinese language preference, Medicaid status, and glaucoma diagnosis; poorer preoperative visual acuity was only weakly correlated with&#xa0;increased social vulnerability.<br><br>CONCLUSIONS: After adjusting for other biomedical&#xa0;and&#xa0;sociodemographic variables, having&#xa0;Medicaid insurance and being a non-English speaker were the factors&#xa0;most notably associated with reduced cataract surgery utilization and poorer preoperative visual acuity. Health insurance and language barriers, as well as other biomedical and sociodemographic factors, may explain a large proportion of the racial disparities in&#xa0;both cataract surgery utilization and preoperative visual acuity observed among Black and Hispanic patients. Chinese-speaking patients with limited English proficiency are a vulnerable subgroup that exhibits lower rates of cataract surgery utilization and higher degrees of visual loss prior to undergoing&#xa0;cataract surgery compared to other Asian patients.},
}
@article {pmid38327497,
year = {2024},
author = {Teng, M and Wang, J and Su, X and Tian, Y and Ye, X and Zhang, Y},
title = {Causal associations between circulating inflammatory cytokines and blinding eye diseases: a bidirectional Mendelian randomization analysis.},
journal = {Frontiers in aging neuroscience},
volume = {16},
number = {},
pages = {1324651},
pmid = {38327497},
issn = {1663-4365},
abstract = {BACKGROUND: Previous studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract and macular degeneration. However, the causality of these associations remains controversial. This study employs a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between 41 circulating inflammatory cytokines and these blinding eye diseases.<br><br>METHODS: Summary data for glaucoma, cataract, macular degeneration and 41 circulating inflammatory cytokines were publicly available. The inverse variance weighted (IVW) method was employed as the main analysis method. Additionally, various sensitivity tests, including MR-Egger regression, weighted median, weight mode, Cochran's Q test, MR pleiotropy Residual Sum and Outlier test, and leave-one-out test, were conducted to evaluate sensitivity and stability of results.<br><br>RESULTS: The IVW analysis identified six circulating inflammatory cytokines causally associated with the risk of blinding eye diseases: Monokine induced by interferon-gamma (MIG) for glaucoma, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, and platelet derived growth factor BB (PDGFbb) for cataract, and MIG and hepatocyte growth factor (HGF) for macular degeneration. However, it is noteworthy that none of these associations remained significant after Bonferroni correction (p <&#x2009;0.0004). Reverse MR analyses indicated that cataract may lead to a decrease in vascular endothelial growth factor (VEGF) levels (OR: 3.326&#x2009;&#xd7;&#x2009;10[-04], 95% CI: 5.198&#x2009;&#xd7;&#x2009;10[-07] -&#x2009;2.129&#x2009;&#xd7;&#x2009;10[-01], p =&#x2009;0.0151).<br><br>CONCLUSION: This study highlights the potential roles of specific inflammatory cytokines in the development of glaucoma, cataract and macular degeneration. Moreover, it suggests that VEGF is likely to be involved in cataract development downstream. These findings offer insights for early prevention and novel therapeutic strategies for these blinding eye diseases.},
}
@article {pmid38326787,
year = {2024},
author = {Park, SW and Kim, KH and Kwon, HJ and Byon, IS and Khan, YH and Nguyen, QD},
title = {Ocular syphilis masquerading as refractory retinal diseases.},
journal = {BMC infectious diseases},
volume = {24},
number = {1},
pages = {165},
pmid = {38326787},
issn = {1471-2334},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Diabetic Retinopathy/drug therapy ; *Macular Edema ; Vascular Endothelial Growth Factor A ; *Syphilis/diagnosis/drug therapy ; *Choroidal Neovascularization/diagnosis/drug therapy ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; *Endophthalmitis/drug therapy ; Intravitreal Injections ; },
abstract = {PURPOSE: To report two cases of syphilis masquerading as chronic refractory macular diseases.<br><br>CASE DESCRIPTIONS: Two patients had been diagnosed with neovascular age-related macular degeneration (neovascular AMD) and diabetic macular edema (DME), respectively. The disease worsened despite repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) and also surgical treatment (in suspected case of DME). Systemic evaluations were positive for syphilis. Intravenous penicillin was started, and the macular diseases improved. The lesions were well controlled afterward.<br><br>CONCLUSIONS: The current two cases demonstrated that ocular syphilis can masquerade as refractory chronic retinal diseases such as DME and neovascular AMD. Laboratory evaluations for syphilis may be needed, not only for uveitis but also for refractory retinal diseases. Indocyanine green angiography may be helpful to reveal occult syphilis.},
}
@article {pmid38326629,
year = {2024},
author = {Borrelli, E and Barresi, C and Berni, A and Viggiano, P and Reibaldi, M and Introini, U and Bandello, F},
title = {OCT risk factors for 2-year foveal involvement in non-treated eyes with extrafoveal geographic atrophy and AMD.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {7},
pages = {2101-2109},
pmid = {38326629},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fovea Centralis/pathology ; Female ; *Geographic Atrophy/diagnosis/etiology ; Male ; Retrospective Studies ; Risk Factors ; Aged ; Follow-Up Studies ; *Visual Acuity ; *Retinal Pigment Epithelium/pathology ; *Fluorescein Angiography/methods ; *Disease Progression ; Fundus Oculi ; Aged, 80 and over ; Time Factors ; Macular Degeneration/diagnosis ; Middle Aged ; },
abstract = {PURPOSE: To assess the relationship of optical coherence tomography (OCT) findings and progression to foveal atrophy in a cohort of eyes with extrafoveal geographic atrophy (GA) and age-related macular degeneration (AMD) at inclusion.<br><br>METHODS: We retrospectively analyzed 45 participants (45 eyes) with extrafoveal GA at baseline and with 2&#xa0;years of regular follow-ups. Several OCT qualitative features (i.e., presence of foveal flat pigment epithelium detachment with a thin double layer sign [DLS] and reticular pseudodrusen, GA focality) and quantitative measurements (outer retinal layer thickness, retinal pigment epithelium [RPE] to Bruch's membrane [BM] volume, minimum distance from the central foveal circle, and untransformed GA lesion size area) were assessed at baseline. Logistic regression analyses were carried out to identify independent significant predictors and compute odds ratios (ORs) for the risk of the development of atrophy.<br><br>RESULTS: At month 24, 26 eyes (57.8%) developed atrophy in the foveal central circle, while 11 eyes (24.4%) developed atrophy in the foveal central point. Significant independent predictive features for the development of atrophy in the foveal central circle included foveal outer retinal thickness (OR, 0.867; p&#x2009;=&#x2009;0.015), minimum distance from the foveal central circle (OR, 0.992; p&#x2009;=&#x2009;0.022), and foveal thin DLS (OR, 0.044; p&#x2009;=&#x2009;0.036). The only independent predictive feature for the development of atrophy in the foveal central point was the presence of foveal thin DLS (OR, 0.138; p&#x2009;=&#x2009;0.017).<br><br>CONCLUSIONS: We identified OCT risk factors for 2-year foveal atrophy in eyes with untreated extrafoveal GA at baseline.},
}
@article {pmid38325906,
year = {2024},
author = {Mahmoudi, A and Manafi, N and Corradetti, G and Gupta Nittala, M and Emamverdi, M and Trejo Corona, S and Wykoff, CC and Sarraf, D and Sadda, SR},
title = {Risk factors for development of hyper-reflective foci overlying drusen in eyes with intermediate age-related macular degeneration.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {9},
pages = {1234-1239},
doi = {10.1136/bjo-2023-324098},
pmid = {38325906},
issn = {1468-2079},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis ; Retrospective Studies ; Female ; Male ; Risk Factors ; Aged ; Case-Control Studies ; Aged, 80 and over ; Macular Degeneration/complications/diagnosis ; Visual Acuity/physiology ; Fluorescein Angiography/methods ; Middle Aged ; Follow-Up Studies ; },
abstract = {AIMS: The aim of this study is to assess baseline characteristics of drusen preceding the development of intraretinal hyper-reflective foci (IHRF) in eyes with intermediate age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective case-control study, longitudinal optical coherence tomography (OCT) volume data from eyes with intermediate AMD in a retina clinic population were screened. All drusen that developed overlying IHRF were marked. A random number generator was used to select for further grading three drusen that did not develop IHRF.<br><br>RESULTS: Ninety eyes (from 72 patients), including 140 drusen with overlying IHRF and 270 IHRF- drusen, were analysed. Greater drusen height, basal drusen width and overlying ellipsoid zone (EZ) and external limiting membrane disruption were associated with a significantly greater risk for IHRF development (p&#x2264;0.001). Regression analysis revealed EZ disruption increased these odds by 4.1 (p&#x2264;0.001). Each 10-&#xb5;m increase in drusen height and width increased the odds by 34% (p&#x2264;0.001) and 3% (p: 0.005), respectively. Each 100-&#xb5;m increase in distance from the fovea decreased the odds by 10% (p: 0.013).<br><br>CONCLUSIONS: The presence of overlying EZ disruption and a greater drusen height substantially increased the risk for IHRF development, whereas drusen further from the fovea indicated reduced risk. Given the importance of IHRF as a biomarker for AMD progression, these findings may be of value in defining patient populations for future early intervention trials.},
}
@article {pmid38324770,
year = {2024},
author = {Naaman, E and Qarawani, A and Ben-Zvi Elimelech, R and Harel, M and Sigal-Dror, S and Safuri, S and Smirnovas, V and Baronaite, I and Romanova, NV and Morozova-Roche, LA and Zayit-Soudry, S},
title = {The Surprising Nonlinear Effects of S100A9 Proteins in the Retina.},
journal = {ACS chemical neuroscience},
volume = {15},
number = {4},
pages = {735-744},
doi = {10.1021/acschemneuro.3c00650},
pmid = {38324770},
issn = {1948-7193},
mesh = {Rats ; Animals ; *Calgranulin B/metabolism ; Retina/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Electroretinography ; Inflammation/metabolism ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a complex disease in which inflammation is implicated as a key factor but the precise molecular mechanisms are poorly understood. AMD lesions contain an excess of the pro-inflammatory S100A9 protein, but its retinal significance was yet unexplored. S100A9 was shown to be intrinsically amyloidogenic in vitro and in vivo. Here, we hypothesized that the retinal effects of S100A9 are related to its supramolecular conformation. ARPE-19 cultures were treated with native dimeric and fibrillar S100A9 preparations, and cell viability was determined. Wild-type rats were treated intravitreally with the S100A9 solutions in the right eye and with the vehicle in the left. Retinal function was assessed longitudinally by electroretinography (ERG), comparing the amplitudes and configurations for each intervention. Native S100A9 had no impact on cellular viability in vitro or on the retinal function in vivo. Despite dispersed intracellular uptake, fibrillar S100A9 did not decrease ARPE-19 cell viability. In contrast, S100A9 fibrils impaired retinal function in vivo following intravitreal injection in rats. Intriguingly, low-dose fibrillar S100A9 induced contrasting in vivo effects, significantly increasing the ERG responses, particularly over 14 days postinjection. The retinal effects of S100A9 were further characterized by glial and microglial cell activation. We provide the first indication for the retinal effects of S100A9, showing that its fibrils inflicted retinal dysfunction and glial activation in vivo, while low dose of the same assemblies resulted in an unpredicted enhancement of the ERG amplitudes. These nonlinear responses highlight the consequences of self-assembly of S100A9 and provide insight into its pathophysiological and possibly physiological roles in the retina.},
}
@article {pmid38324301,
year = {2024},
author = {Kontoh-Twumasi, R and Budkin, S and Edupuganti, N and Vashishtha, A and Sharma, S},
title = {Role of Serine Protease Inhibitors A1 and A3 in Ocular Pathologies.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {2},
pages = {16},
pmid = {38324301},
issn = {1552-5783},
support = {P30 EY031631/EY/NEI NIH HHS/United States ; R01 EY026936/EY/NEI NIH HHS/United States ; },
mesh = {Antioxidants ; Apoptosis ; Eye ; Liver ; Humans ; *Eye Diseases/genetics ; *Serpins/genetics ; },
abstract = {Serine protease inhibitors A1 (SerpinA1) and A3 (SerpinA3) are important members of the serpin family, playing crucial roles in the regulation of serine proteases and influencing various physiological processes. SerpinA1, also known as α-1-antitrypsin, is a versatile glycoprotein predominantly synthesized in the liver, with additional production in inflammatory and epithelial cell types. It exhibits multifaceted functions, including immune modulation, complement activation regulation, and inhibition of endothelial cell apoptosis. SerpinA3, also known as α-1-antichymotrypsin, is expressed both extracellularly and intracellularly in various tissues, particularly in the retina, kidney, liver, and pancreas. It exerts anti-inflammatory, anti-angiogenic, antioxidant, and antifibrotic activities. Both SerpinA1 and SerpinA3 have been implicated in conditions such as keratitis, diabetic retinopathy, age-related macular degeneration, glaucoma, cataracts, dry eye disease, keratoconus, uveitis, and pterygium. Their role in influencing metalloproteinases and cytokines, as well as endothelial permeability, and their protective effects on Müller cells against oxidative stress further highlight their diverse and critical roles in ocular pathologies. This review provides a comprehensive overview of the etiology and functions of SerpinA1 and SerpinA3 in ocular diseases, emphasizing their multifaceted roles and the complexity of their interactions within the ocular microenvironment.},
}
@article {pmid38322501,
year = {2024},
author = {Kamao, H and Mitsui, E and Date, Y and Goto, K and Mizukawa, K and Miki, A},
title = {The Effect of a Loading Dose Regimen in the Switch to Brolucizumab for Patients with Aflibercept-Resistant nAMD.},
journal = {Journal of ophthalmology},
volume = {2024},
number = {},
pages = {3673930},
pmid = {38322501},
issn = {2090-004X},
abstract = {PURPOSE: To evaluate the one-year outcomes of switching to brolucizumab with and without a loading dose regimen (three monthly injections) in eyes with aflibercept-resistant neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We retrospectively studied nAMD patients who had retinal exudate under bimonthly injections of aflibercept and were switched to brolucizumab from aflibercept. Patients were grouped into intravitreal brolucizumab injection (IVBr) with a loading dose regimen (loading group) and without a loading dose regimen (nonloading group). We assessed the best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SFCT), IVBr status (number of injections and last injection interval), and retinal exudate status on optical coherence tomography.<br><br>RESULTS: Overall, 52 eyes received &#x2265;1 IVBr; 26 eyes received &#x2265;3 IVBr with&#x2009;12-month follow-up. A total of 13 eyes in the loading group and 13 eyes in the nonloading group were reviewed. One year after switching, BCVA changed from 0.28&#x2009;&#xb1;&#x2009;0.25 to 0.19&#x2009;&#xb1;&#x2009;0.28 in the loading group (P=0.28) and from 0.25&#x2009;&#xb1;&#x2009;0.20 to 0.23&#x2009;&#xb1;&#x2009;0.25 in the nonloading group (P=0.92). The mean CRT decreased from 263.6&#x2009;&#xb1;&#x2009;40.7&#x2009;&#xb5;m to 221.7&#x2009;&#xb1;&#x2009;54.6&#x2009;&#xb5;m in the loading group (P=0.03), while it only changed from 244.9&#x2009;&#xb1;&#x2009;77.2&#x2009;&#xb5;m to 221.0&#x2009;&#xb1;&#x2009;78.7&#x2009;&#xb5;m in the nonloading group (P=0.26). Both the loading and nonloading groups achieved 69% dry macula. The number of injections received was significantly higher in the loading group (7.6&#x2009;&#xb1;&#x2009;0.6 vs. 6.8&#x2009;&#xb1;&#x2009;0.4, P&#x2009; < &#x2009;0.001). Two patients (4.2%) developed intraocular inflammation.<br><br>CONCLUSION: Switching to brolucizumab from aflibercept for eyes with nAMD with resistance to bimonthly injections of aflibercept is a valuable treatment option with and without the loading regimen. This trial is registered with UMIN000023676.},
}
@article {pmid38321224,
year = {2024},
author = {Zegeye, Y and Aredo, B and Yuksel, S and Kirman, DC and Kumar, A and Chen, B and Turpin, E and Shresta, S and He, YG and Gautron, L and Tang, M and Li, X and DiCesare, SM and Hulleman, JD and Xing, C and Ludwig, S and Moresco, EMY and Beutler, BA and Ufret-Vincenty, RL},
title = {E3 ubiquitin ligase Herc3 deficiency leads to accumulation of subretinal microglia and retinal neurodegeneration.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {3010},
pmid = {38321224},
issn = {2045-2322},
support = {R01 EY033181/EY/NEI NIH HHS/United States ; P30 EY030413/EY/NEI NIH HHS/United States ; P30 EY020799/EY/NEI NIH HHS/United States ; AI125581/NH/NIH HHS/United States ; R01 AI125581/AI/NIAID NIH HHS/United States ; EY030413/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; *Microglia/metabolism ; Retina/pathology ; *Retinal Degeneration/pathology ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitins/metabolism ; },
abstract = {Activated microglia have been implicated in the pathogenesis of age-related macular degeneration (AMD), diabetic retinopathy, and other neurodegenerative and neuroinflammatory disorders, but our understanding of the mechanisms behind their activation is in infant stages. With the goal of identifying novel genes associated with microglial activation in the retina, we applied a semiquantitative fundus spot scoring scale to an unbiased, state-of-the-science mouse forward genetics pipeline. A mutation in the gene encoding the E3 ubiquitin ligase Herc3 led to prominent accumulation of fundus spots. CRISPR mutagenesis was used to generate Herc3[-/-] mice, which developed prominent accumulation of fundus spots and corresponding activated Iba1 + /CD16 + subretinal microglia, retinal thinning on OCT and histology, and functional deficits by Optomotory and electrophysiology. Bulk RNA sequencing identified activation of inflammatory pathways and differentially expressed genes involved in the modulation of microglial activation. Thus, despite the known expression of multiple E3 ubiquitin ligases in the retina, we identified a non-redundant role for Herc3 in retinal homeostasis. Our findings are significant given that a dysregulated ubiquitin-proteasome system (UPS) is important in prevalent retinal diseases, in which activated microglia appear to play a role. This association between Herc3 deficiency, retinal microglial activation and retinal degeneration merits further study.},
}
@article {pmid38320691,
year = {2024},
author = {Shukla, P and Russell, MW and Muste, JC and Shaia, JK and Kumar, M and Nowacki, AS and Hajj-Ali, RA and Singh, RP and Talcott, KE},
title = {Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {8},
pages = {778-785},
doi = {10.1016/j.oret.2024.01.026},
pmid = {38320691},
issn = {2468-6530},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cross-Sectional Studies ; Incidence ; *Inflammation/complications ; *Macular Degeneration/complications/diagnosis/epidemiology ; *Propensity Score ; Retrospective Studies ; Risk Assessment/methods ; Risk Factors ; United States/epidemiology ; },
abstract = {PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD.<br><br>DESIGN: Cross-sectional study and cohort study.<br><br>SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts.<br><br>METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design.<br><br>MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID.<br><br>RESULTS: After propensity score matching, AMD and control cohorts (n&#xa0;= 217 197 each) had a mean &#xb1; standard deviation age of 74.7 &#xb1; 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls.<br><br>CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38319554,
year = {2024},
author = {Grisanti, S and Bartz-Schmidt, KU and Heimann, H and Lommatzsch, A and Walter, P and Ach, T},
title = {Letter to the Editor Regarding "LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration".},
journal = {Ophthalmology and therapy},
volume = {13},
number = {4},
pages = {1051-1053},
pmid = {38319554},
issn = {2193-8245},
}
@article {pmid38319553,
year = {2024},
author = {Burton, B and Munk, MR and Tedford, SE and Croissant, CL and Rückert, R and Tedford, CE},
title = {A Response to: Letter to the Editor Regarding "LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration".},
journal = {Ophthalmology and therapy},
volume = {13},
number = {4},
pages = {1055-1060},
pmid = {38319553},
issn = {2193-8245},
}
@article {pmid38319061,
year = {2024},
author = {Gong, D and Ross, C and Hall, N and Ivanov, A and Elze, T and Sobrin, L and Miller, JW and Lorch, A and Miller, JB and , },
title = {Fellow Eyes Conversion Rates in Patients With Unilateral Exudative Age-Related Macular Degeneration: An Academy IRIS[®] Registry Analysis.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {4},
pages = {220-226},
doi = {10.3928/23258160-20240125-01},
pmid = {38319061},
issn = {2325-8179},
mesh = {Humans ; Female ; Male ; Retrospective Studies ; *Wet Macular Degeneration/diagnosis ; *Registries ; Aged ; Disease Progression ; Aged, 80 and over ; Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Choroidal Neovascularization/diagnosis ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND AND OBJECTIVE: This study aimed to examine conversion rates from non-exudative to exudative age-related macular degeneration (AMD) in the fellow eye of patients with unilateral exudative AMD using the Academy IRIS[®] Registry.<br><br>PATIENTS AND METHODS: This study was a retrospective, cohort analysis from 2016 to 2019. Patient and disease characteristics including initial AMD stage were collected. Cox proportional-hazard (PH) and logistic regression modeling were performed.<br><br>RESULTS: The risk of conversion was lower for men relative to women and for Asians and Blacks relative to Whites. Compared to never-smokers, active smokers were at increased risk of conversion, and compared to initially early non-exudative AMD eyes, intermediate and advanced non-exudative AMD eyes had higher rates of conversion. Compared to active choroidal neovascularization eyes, eyes with inactive choroidal neovascularization and inactive scars had lower rates of fellow eye conversion.<br><br>CONCLUSIONS: In this cohort analysis of unilateral exudative AMD patients, women, Whites, and active smokers had higher rates of non-exudative to exudative AMD conversion in the fellow eye. [Ophthalmic Surg Lasers Imaging Retina 2024;55:220-226.].},
}
@article {pmid38319060,
year = {2024},
author = {de Asís Bartol-Puyal, F and Monroy, JS and Bayod, MP and Moreno, &#xd3;R and Calvo, P and Pablo, L},
title = {Assistance Burden Comparison Between Age-Related Macular Degeneration and Retinal Angiomatous Proliferation Over a Three-Year Follow-up.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {4},
pages = {197-203},
doi = {10.3928/23258160-20240118-01},
pmid = {38319060},
issn = {2325-8179},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Follow-Up Studies ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Intravitreal Injections ; Aged, 80 and over ; *Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; Retinal Neovascularization/diagnosis/drug therapy ; Ranibizumab/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography/methods ; Time Factors ; },
abstract = {BACKGROUND AND OBJECTIVE: We compared assistance burden between neovascular age-related macular degeneration (nAMD) and retinal angiomatous proliferation (RAP) under intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment on a treat-and-extend (T&amp;E) regimen in a third-level hospital in a developed country.<br><br>PATIENTS AND METHODS: This retrospective study using data from the Fight Retinal Blindness! Registry included patients treated between January 2016 and December 2020. Final event was established as best corrected visual acuity (BCVA) lower than 20 Early Treatment Diabetic Retinopathy Study letters. According to choroidal neovascularization (CNV), three different study groups were established: type 1, 2, and 3.<br><br>RESULTS: A total of 285 eyes of 227 patients were included. Mean age was 80.1 &#xb1; 6.5, 79.1 &#xb1; 7.9, and 81.2 &#xb1; 7.2 years, for the three study groups, respectively. Mean injections were 16.0 &#xb1; 4.8, 16.5 &#xb1; 4.1, and 14.1 &#xb1; 5.7, respectively; and mean number of visits were 17.9 &#xb1; 4.3, 18.2 &#xb1; 3.1, and 16.8 &#xb1; 5.3, respectively. No differences were found (P > 0.05). Survival curves and log-rank analysis also showed no differences (P = 0.344). Cox proportional hazard models showed that a lower baseline BCVA, subfoveal geographic atrophy (GA), and subfoveal fibrosis (SF) were associated with a higher risk of reaching &#x2264; 20 letters.<br><br>CONCLUSIONS: nAMD and RAP under a T&amp;E regimen indicate a high assistance burden during the first three years. The presence of subfoveal GA or SF are associated with a BCVA lower than 20 letters. [Ophthalmic Surg Lasers Imaging Retina 2024;55:197-203.].},
}
@article {pmid38319056,
year = {2024},
author = {Gupta, U and Maatouk, CM and Markle, JC and Talcott, KE and Singh, RP and Rachitskaya, AV},
title = {Characterizing the Journey of Geographic Atrophy Patients in Routine Ophthalmic Practice.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {4},
pages = {204-210},
doi = {10.3928/23258160-20240123-02},
pmid = {38319056},
issn = {2325-8179},
mesh = {Humans ; *Geographic Atrophy/diagnosis/physiopathology ; Retrospective Studies ; Female ; Male ; *Visual Acuity ; Aged ; Aged, 80 and over ; Ophthalmology ; Disease Progression ; Middle Aged ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND AND OBJECTIVE: Geographic atrophy (GA) is a form of late-stage age-related macular degeneration (AMD). This study aims to characterize the journey of patients with GA in real-world ophthalmology practice.<br><br>PATIENTS AND METHODS: This is a retrospective cohort study of 100 patients with GA and 100 with intermediate AMD (iAMD).<br><br>RESULTS: Approximately one-third of GA patients' eyes had GA at the time of their initial AMD diagnosis, and nearly half of the iAMD patients' eyes had iAMD at that time. When holding confounders constant, GA patients experienced significantly worse visual acuity outcomes, and a significantly higher proportion required referrals for low vision evaluation, needed assistance for activities of daily living, failed to meet driving standards, and met criteria for legal blindness when compared to iAMD controls.<br><br>CONCLUSIONS: Many patients have already progressed to GA by the time they receive an AMD diagnosis, emphasizing the importance of providing early detection and intervention, especially considering novel treatment options. [Ophthalmic Surg Lasers Imaging Retina 2024;55:204-210.].},
}
@article {pmid38318988,
year = {2024},
author = {Yetisgin, AA and Durak, S and Kutlu, O and Cetinel, S},
title = {Hyaluronan-Sphingosine Polymersomes for Treatment of Ocular Neovascularization: Synthesis and Evaluation.},
journal = {Macromolecular bioscience},
volume = {24},
number = {6},
pages = {e2300531},
doi = {10.1002/mabi.202300531},
pmid = {38318988},
issn = {1616-5195},
support = {118C146//Scientific and Technological Research Council of T&#xfc;rkiye/ ; },
mesh = {*Hyaluronic Acid/chemistry/pharmacology ; Humans ; Animals ; *Human Umbilical Vein Endothelial Cells ; Swine ; *Sphingosine/analogs &amp; derivatives/pharmacology/chemistry ; Cell Proliferation/drug effects ; Retinal Pigment Epithelium/drug effects/metabolism ; Retinal Neovascularization/drug therapy/pathology ; },
abstract = {Ocular neovascularization is a hallmark of several sight-threatening diseases, including diabetic retinopathy and age-related macular degeneration. Currently, available treatments are limited and often associated with side effects. Therefore, a novel approach to ocular neovascularization treatment through utilization of polymersomes from self-assembled sphingosine-grafted hyaluronic acid (HA-Sph) amphiphilic polymers is presented. The polymersomes are generated in spherical morphologies and sizes between 97.95 - 161.9 nm with homogenous size distributions. Experiments reveal that HA-Sph polymersomes, with concentrations ≥150 µg mL[-1], significantly inhibit the proliferation of human umbilical vein endothelial cells (HUVECs), while concurrently promoting the proliferation of retinal pigment epithelial cells. The polymersomes demonstrate gradual disintegration in vitro, leading to sustained release of sphingosine, which prolongs the inhibition of HUVEC proliferation (from 87.5% at 24 h to 35.2% viability at 96 h). The efficacy of polymersomes in inhibiting angiogenesis is confirmed through tube formation assay, revealing a substantial reduction in tube length compared to the control group. The findings also validate the ocular penetration capability of polymersomes through ex vivo whole porcine eye ocular penetration study, indicating their suitability for topical administration. Potentially, HA-Sph polymersomes can be harnessed to develop intricate drug delivery systems that protect the retina and effectively treat ocular diseases.},
}
@article {pmid38317867,
year = {2024},
author = {Kostolna, K and Reiter, GS and Frank, S and Coulibaly, LM and Fuchs, P and Röggla, V and Gumpinger, M and Leitner Barrios, GP and Mares, V and Bogunovic, H and Schmidt-Erfurth, U},
title = {A Systematic Prospective Comparison of Fluid Volume Evaluation across OCT Devices Used in Clinical Practice.},
journal = {Ophthalmology science},
volume = {4},
number = {3},
pages = {100456},
pmid = {38317867},
issn = {2666-9145},
abstract = {OBJECTIVE: Treatment decisions in neovascular age-related macular degeneration (nAMD) are mainly based on subjective evaluation of OCT. The purpose of this cross-sectional study was to provide a comparison of qualitative and quantitative differences between OCT devices in a systematic manner.<br><br>DESIGN: Prospective, cross-sectional study.<br><br>SUBJECTS: One hundred sixty OCT volumes, 40 eyes of 40 patients with nAMD.<br><br>METHODS: Patients from clinical practice were imaged with 4 different OCT devices during one visit: (1) Spectralis Heidelberg; (2) Cirrus; (3) Topcon Maestro2; and (4) Topcon Triton. Intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were manually annotated in all cubes by trained human experts to establish fluid measurements based on expert-reader annotations. Intraretinal fluid, SRF, and PED volume were quantified in nanoliters (nL). Bland-Altman plots were created to analyze the agreement of measurements in the central 1 and 6 mm. The Friedman test was performed to test for significant differences in the central 1, 3, and 6&#xa0;mm.<br><br>MAIN OUTCOME MEASURES: Intraretinal fluid, SRF, and PED volume.<br><br>RESULTS: In the central 6 mm, there was a trend toward higher IRF and PED volumes in Spectralis images compared with the other devices and no differences in SRF volume. In the central 1 mm, the standard deviation of the differences ranged from &#xb1;&#x2009;3 nL to &#xb1;&#x2009;6 nL for IRF, from &#xb1;&#x2009;3 nL to &#xb1;&#x2009;4 nL for SRF, and from &#xb1;&#x2009;7 nL to &#xb1;&#x2009;10 nL for PED in all pairwise comparisons. Manually annotated IRF and SRF volumes showed no significant differences in the central 1 mm.<br><br>CONCLUSIONS: Fluid volume quantification achieved excellent reliability in all 3 retinal compartments on images obtained from 4 OCT devices, particularly for clinically relevant IRF and SRF values. Although fluid volume quantification is reliable in all 4 OCT devices, switching OCT devices might lead to deviating fluid volume measurements with higher agreement in the central 1 mm compared with the central 6 mm, with highest agreement for SRF volume in the central 1 mm. Understanding device-dependent differences is essential for expanding the interpretation and implementation of pixel-wise fluid volume measurements in clinical practice and in clinical trials.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38316703,
year = {2024},
author = {Honjo, J and Mukai, R and Itagaki, K and Tanaka, K and Norikawa, K and Kato, Y and Kasai, A and Sugano, Y and Sekiryu, T},
title = {Intraocular pressure changes during intravitreal aflibercept injection based on treat-and-extend regimen in Japanese patients with neovascular age-related macular degeneration and glaucoma.},
journal = {Japanese journal of ophthalmology},
volume = {68},
number = {2},
pages = {91-95},
pmid = {38316703},
issn = {1613-2246},
mesh = {Humans ; Angiogenesis Inhibitors ; *Glaucoma/drug therapy ; Intraocular Pressure ; Intravitreal Injections ; Japan/epidemiology ; *Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins/therapeutic use ; Retrospective Studies ; },
abstract = {PURPOSE: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2&#xa0;mg/0.05&#xa0;ml of aflibercept and followed for 52&#xa0;weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52&#xa0;weeks were recorded.<br><br>RESULTS: The mean of aflibercept injections was 8.3 &#xb1; 1.9. The mean IOP at baseline was 14.0 &#xb1; 3.1&#xa0;mmHg, and the mean IOP after aflibercept therapy was 13.0 &#xb1; 2.4&#xa0;mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery.<br><br>CONCLUSION: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma.},
}
@article {pmid38315351,
year = {2024},
author = {Sasso, P and Savastano, A and Vidal-Aroca, F and Minnella, AM and Francione, G and Sammarco, L and Cima, V and Ghiraldelli, R and Mattei, R and Rizzo, S},
title = {Correction: Enhancing the Functional Performance of Patients with Late-Stage Age-Related Macular Degeneration Implanted with a Miniature Telescope using Rehabilitation Training.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {3},
pages = {709},
doi = {10.1007/s40123-024-00890-6},
pmid = {38315351},
issn = {2193-8245},
}
@article {pmid38315350,
year = {2024},
author = {Sha, F and Li, H and Zhang, L and Liang, F},
title = {Evidence for Genetic Causal Relationships Between Multiple Immune-Mediated Inflammatory Diseases and Age-Related Macular Degeneration: A Univariable and Multivariable Mendelian Randomization Study.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {4},
pages = {955-967},
pmid = {38315350},
issn = {2193-8245},
support = {82205197//National Natural Science Foundation of China/ ; 82174442//National Natural Science Foundation of China/ ; },
abstract = {INTRODUCTION: With the global aging population on the rise, age-related macular degeneration (AMD) poses a growing healthcare burden. Prior research hints at immune-mediated inflammatory diseases (IMIDs) potentially elevating AMD risk via diverse mechanisms. However, causality remains disputed as a result of confounding factors. Hence, our Mendelian randomization (MR) study aims to untangle this link, mitigating confounding effects to explore the IMID-AMD causal relationship. This study aims to investigate the causal relationship between IMIDs and AMD, providing new strategies for the prevention and treatment of AMD in clinical practice.<br><br>METHODS: This study was registered with PROSPERO, CRD42023469815. We obtained data on IMIDs and AMD from Genome-Wide Association Studies (GWAS) summary statistics and the FinnGen consortium. Rigorous selection steps were applied to screen for eligible instrumental single nucleotide polymorphisms (SNPs). We conducted univariate Mendelian randomization, inverse variance-weighted (IVW), weighted median, Mendelian randomization-Egger (MR-Egger), and multivariate Mendelian randomization (MVMR) analyses. Various sensitivity analysis methods were employed to assess pleiotropy and heterogeneity. The aim was to explore the causal relationships between IMIDs and AMD.<br><br>RESULTS: The MR analysis revealed that Crohn's disease (CD) (IVW: odd ratios (OR) 1.05, 95%&#xa0;CI (confidence interval) 1.01-1.10, p&#x2009;=&#x2009;0.007), rheumatoid arthritis (RA) (IVW: OR 1.09, 95%&#xa0;CI 1.04-1.15, p&#x2009;=&#x2009;0.0001), and type&#xa0;1 diabetes (T1D) (IVW: OR 1.05, 95%&#xa0;CI 1.02-1.09, p&#x2009;=&#x2009;0.001) were correlated with an elevated risk of AMD, while multiple sclerosis (MS) (IVW: OR 2.78E-18, 95%&#xa0;CI 2.23E-31 to 3.48E-05, p&#x2009;=&#x2009;0.008) appeared to be protective against AMD. These findings were supported by an array of MR analysis methodologies and the MVMR approach.<br><br>CONCLUSION: Our study results, based on MR, provide genetic evidence indicating a causal relationship between specific IMIDs and AMD. CD, RA, and T1D are factors increasing the risk of AMD, while MS may have a protective effect.},
}
@article {pmid38313400,
year = {2024},
author = {Thinggaard, BS and Frederiksen, K and Subhi, Y and Möller, S and Sørensen, TL and Kawasaki, R and Grauslund, J and Stokholm, L},
title = {VEGF Inhibition Associates With Decreased Risk of Mortality in Patients With Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {3},
pages = {100446},
pmid = {38313400},
issn = {2666-9145},
abstract = {PURPOSE: Controversy exists regarding the systemic safety of intravitreal VEGF inhibitors in the treatment of neovascular age-related macular degeneration (nAMD). We aimed to investigate the potential impact of VEGF inhibitor treatment on the risk of all-cause mortality and cardiovascular disease (CVD) among patients with nAMD.<br><br>DESIGN: A nationwide register-based cohort study with 16 years follow-up.<br><br>PARTICIPANTS: Patients with nAMD exposed with VEGF inhibitors (n&#xa0;=&#xa0;37&#x2009;733) and unexposed individuals without nAMD (n&#xa0;=&#xa0;1&#x2009;897&#x2009;073) aged &#x2265; 65 years residing in Denmark between January 1, 2007, and December 31,&#xa0;2022.<br><br>METHODS: Cox proportional hazards analysis was conducted to assess the effect of intravitreal VEGF inhibitor treatment on all-cause mortality and incident CVD.<br><br>MAIN OUTCOME MEASURES: In a predefined analysis plan we defined primary outcomes as hazard ratios (HRs) of all-cause mortality and a composite CVD endpoint in patients with nAMD treated with VEGF inhibitors compared with individuals without nAMD. The secondary outcomes encompassed analyses that explored the impact of the number of doses and the association between exposure and outcome over a specific time period.<br><br>RESULTS: Overall, 63.7% of patients with nAMD were women with an average age of 69.9 years (interquartile range 65.0-76.0 years). Patients exposed to VEGF inhibitors demonstrated a reduced risk of all-cause mortality compared with individuals without nAMD (HR, 0.79; 95% confidence interval [CI], 0.78-0.81), and an increased risk of composite CVD (HR, 1.04; 95% CI, 1.01-1.07). The decreased risk of all-cause mortality persisted, but there was no significant association between VEGF inhibitor treatment and CVD when patients with nAMD were grouped by the number of doses or considered exposed within 60 days postinjection.<br><br>CONCLUSIONS: Our study revealed a decreased risk of all-cause mortality and a 4% increased risk of CVD among patients with nAMD exposed with VEGF inhibitors. The decreased risk of mortality is unlikely to be directly pathophysiologically related to VEGF inhibitor treatment. Instead, we speculate that patients undergoing VEGF inhibitor treatment are, on average, individuals in good health with adequate personal resources. Therefore, they also have a higher likelihood of overall survival. These findings strongly support the safety of VEGF inhibitor treatment in terms of all-cause mortality and CVD among patients with nAMD.<br><br>FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid38311207,
year = {2024},
author = {Künzel, SH and Broadbent, E and Möller, PT and Lindner, M and Goerdt, L and Czauderna, J and Schmitz-Valckenberg, S and Holz, FG and Pfau, M and Fleckenstein, M},
title = {Association of Lesion Location and Functional Parameters with Vision-Related Quality of Life in Geographic Atrophy Secondary to Age-related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {8},
pages = {794-803},
doi = {10.1016/j.oret.2024.01.025},
pmid = {38311207},
issn = {2468-6530},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY033365/EY/NEI NIH HHS/United States ; R01 EY034965/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Quality of Life ; *Geographic Atrophy/diagnosis/etiology/physiopathology ; Prospective Studies ; *Visual Acuity ; Male ; Female ; Aged ; *Macular Degeneration/complications/diagnosis/physiopathology ; Surveys and Questionnaires ; *Tomography, Optical Coherence/methods ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; Fluorescein Angiography/methods ; Fundus Oculi ; },
abstract = {OBJECTIVE: The primary goal of this study was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients suffering from geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>DESIGN: This study was designed as a prospective, noninterventional, natural-history study (Directional Spread in Geographic-Atrophy study, NCT02051998).<br><br>SUBJECTS: The research involved 82 patients with bilateral GA.<br><br>METHODS: The study examined parameters including GA location as assessed by the ETDRS grid, best-corrected visual acuity, low-luminance visual acuity (LLVA), reading acuity, and speed. These parameters were then correlated with VRQoL, which was gauged using the National Eye Institute Visual Function Questionnaire 25. The analysis method employed was the least absolute shrinkage and selection operator with linear mixed-effects models.<br><br>MAIN OUTCOME MEASURES: The central parameters measured in this study encompassed GA area, VRQoL scores associated with different GA subfields, and the significance of LLVA for foveal-sparing patients.<br><br>RESULTS: On average, patients showed a total GA area of 2.9 &#xb1; 1.2 mm[2] in the better eye (BE) and 3.1 &#xb1; 1.3 mm[2] in the worse eye. The most significant associations with VRQoL scores for distance and near activities were observed in the inner lower and inner left subfields of the BE, respectively. For patients with foveal-sparing GA, the LLVA of the BE stood out as the most influential variable across all VRQoL scales.<br><br>CONCLUSIONS: The study's findings point toward the pivotal role of GA location, especially the inner lower and inner left subfields of the BE, in relation to VRQoL in GA patients. The LLVA's importance becomes even more pronounced for foveal-sparing patients. These observations highlight the need for health care professionals to better understand the association between lesion location and patient-reported outcomes. This is critical for informing treatment decisions and refining the planning of interventional trials.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38309537,
year = {2024},
author = {Liu, Z and Huang, J and Li, D and Zhang, C and Wan, H and Zeng, B and Tan, Y and Zhong, F and Liao, H and Liu, M and Chen, ZS and Zou, C and Liu, D and Qin, B},
title = {Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.},
journal = {Free radical biology &amp; medicine},
volume = {214},
number = {},
pages = {42-53},
doi = {10.1016/j.freeradbiomed.2024.01.053},
pmid = {38309537},
issn = {1873-4596},
mesh = {Animals ; Humans ; Mice ; Disease Models, Animal ; *Ferroptosis/genetics ; *Macular Degeneration/genetics ; Retina ; *Retinal Degeneration/chemically induced/genetics/prevention &amp; control ; Retinal Pigments ; },
abstract = {The degeneration of retinal pigment epithelium (RPE) plays an important role in the development of age-related macular degeneration (AMD). However, the underlying mechanism remains elusive. In this study, we identified that ZIP8, a metal-ion transporter, plays a crucial role in the degeneration of RPE cells mediated by ferroptosis. ZIP8 was found to be upregulated in patients with AMD through transcriptome analysis. Upregulated ZIP8 was also observed in both oxidative-stressed RPE cells and AMD mouse model. Importantly, knockdown of ZIP8 significantly inhibited ferroptosis in RPE cells induced by sodium iodate-induced oxidative stress. Blocking ZIP8 with specific antibodies reversed RPE degeneration and restored retinal function, improving visual loss in a mouse model of NaIO3-induced. Interestingly, the modification of the N-glycosylation sites N40, N72 and N88, but not N273, was essential for the intracellular iron accumulation mediated by ZIP8, which further led to increased lipid peroxidation and RPE death. These findings highlight the critical role of ZIP8 in RPE ferroptosis and provide a potential target for the treatment of diseases associated with retinal degeneration, including AMD.},
}
@article {pmid38308362,
year = {2024},
author = {Kanadani, T and Rabelo, N and Takahashi, D and Magalhães, L and Farah, M},
title = {Comparison of antiangiogenic agents (ranibizumab, aflibercept, bevacizumab and ziv-aflibercept) in the therapeutic response to the exudative form of age-related macular degeneration according to the treat-and-extend protocol- true head-to-head study.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {13},
pmid = {38308362},
issn = {2056-9920},
abstract = {PURPOSE: To evaluate the structural and functional changes in eyes with neovascular age related macular degeneration (nAMD) in a real-world setting, using Treat and Extend protocol (T&amp;E), comparing four antiangiogenic agents.<br><br>METHODS: Prospective, observational, case series study performed in 131 patients with the exudative form of nAMD. Patients were randomly assigned into four groups according to the antiangiogenic agent. During the first year, all eyes received at least 3 monthly intravitreal injections of antiangiogenic agents, and afterwards, were submitted to the T&amp;E.<br><br>RESULTS: There was statistically significant difference (p&#x2009;<&#x2009;0.05) between pre- and post-treatment in the best corrected visual acuity measurements by drug used. Patients who used aflibercept had significantly fewer injections than patients using the other drugs (mean&#x2009;=&#x2009;9.03). No significant difference was observed between the drugs bevacizumab, ranibizumab and ziv-aflibercept. With regard to biomarkers, patients who used aflibercept and had lower baseline central retinal thickness, absence of hyperreflective foci and no subretinal hyperreflective material had the lowest number of injections.<br><br>CONCLUSION: Results indicate that over 2&#xa0;years, Intravitreal aflibercept on T&amp;E provided better visual and anatomical improvements when compared to other drugs used in this study with significantly fewer injections.},
}
@article {pmid38307466,
year = {2024},
author = {Yu, C and Robman, L and He, W and Woods, RL and Phuong Thao, LT and Wolfe, R and Phung, J and Makeyeva, GA and Hodgson, LAB and McNeil, JJ and Guymer, RH and MacGregor, S and Lacaze, P},
title = {Predictive Performance of an Updated Polygenic Risk Score for Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {131},
number = {8},
pages = {880-891},
doi = {10.1016/j.ophtha.2024.01.033},
pmid = {38307466},
issn = {1549-4713},
mesh = {Humans ; Male ; Female ; Aged ; Cross-Sectional Studies ; Risk Factors ; *Macular Degeneration/genetics/diagnosis ; *Genome-Wide Association Study ; Aged, 80 and over ; *ROC Curve ; Polymorphism, Single Nucleotide ; Area Under Curve ; Risk Assessment/methods ; Genetic Predisposition to Disease ; Multifactorial Inheritance ; Predictive Value of Tests ; Genotype ; Genetic Risk Score ; },
abstract = {PURPOSE: A recent genome-wide association study of age-related macular degeneration (AMD) identified new AMD-associated risk variants. These variants now can be incorporated into an updated polygenic risk score (PRS). This study aimed to assess the performance of an updated PRS, PRS2023, in an independent cohort of older individuals with retinal imaging data and to compare performance with an older PRS, PRS2016.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: A total of 4175 participants of European ancestry, 70 years of age or older, with genotype and retinal imaging data.<br><br>METHODS: We used logistic regression models and area under the receiver operating characteristic curve (AUC) to assess the performance of PRS2023 compared with PRS2016. AMD status and severity were graded using color fundus photography.<br><br>MAIN OUTCOME MEASURES: Association of PRS2023 and PRS2016 with AMD risk at baseline.<br><br>RESULTS: At enrollment among 4175 participants, 2605 participants (62.4%) had no AMD and 853 participants (20.4%), 671 participants (16.1%), and 46 participants (1.1%) had early, intermediate, and late-stage AMD, respectively. More than 27% of the participants with a high PRS2023 (top quartile) had intermediate or late-stage AMD, compared with < 15% for those in the middle 2 quartiles and less than 13% for those in the lowest quartile. Both PRS2023 and PRS2016 were associated significantly with AMD after adjustment for age, sex, smoking status, and lipid levels, with increasing odds ratios (ORs) for worsening AMD grades. PRS2023 outperformed PRS2016 (P&#xa0;= 0.03 for all AMD and P&#xa0;= 0.03 for late AMD, DeLong test comparing AUC). PRS2023 was associated with late-stage AMD with an adjusted OR of 5.05 (95% confidence interval [CI], 3.41-7.47) per standard deviation. The AUC of a model containing conventional or nongenetic risk factors and PRS2023 was 91% (95% CI, 87%-95%) for predicting late-stage AMD, which improved 12% over the model without the PRS (AUC, 79%; P < 0.001 for difference).<br><br>CONCLUSIONS: A new PRS, PRS2023, for AMD outperforms a previous PRS and predicts increasing risk for late-stage AMD (with stronger association for more severe imaging-confirmed AMD grades). Our findings have clinical implications for the improved prediction and risk stratification of AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38304945,
year = {2024},
author = {Browning, AC and Grinton, ME and Quinn, S and Jain, T and Manikavasagar, V and Aftab, AM},
title = {Long term follow up of patients with MNV3 treated with intra-vitreal Aflibercept.},
journal = {European journal of ophthalmology},
volume = {34},
number = {5},
pages = {1562-1568},
doi = {10.1177/11206721241229912},
pmid = {38304945},
issn = {1724-6016},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage ; *Intravitreal Injections ; *Visual Acuity/physiology ; *Tomography, Optical Coherence ; Prospective Studies ; Male ; Female ; Aged ; Follow-Up Studies ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Fluorescein Angiography ; Angiogenesis Inhibitors/administration &amp; dosage ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Time Factors ; Fundus Oculi ; },
abstract = {PURPOSE: MNV3 or Retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (nAMD). We present the 5 year long term visual and anatomical outcomes of patients with MNV3 lesions treated with intravitreal Aflibercept.<br><br>METHODS: This is a prospective study of treatment na&#xef;ve patients with reading centre graded MNV3 lesions. After the loading phase, the patients received intravitreal Aflibercept as per the View study up to year 3, thereafter it was given on a prn basis. At each visit, best corrected visual acuity (BCVA) and optical coherence tomography (OCT) central macular thickness (CMT) was measured.<br><br>RESULTS: Thirty one patients reached study completion. Mean BCVA of treated eyes had decreased by 0.6 ETDRS letters at the end of year 5 compared with baseline. At study completion, 81% of eyes had stable vision while 19% of eyes had gained 15 letters or more. At study end, 26% of eyes had BCVA of 6/12 or better, while 19% had lost 15 letters or more (all had central foveal photoreceptor loss). There was a maximal mean reduction in CMT of 164 microns (p&#x2009;=&#x2009;<0.0001) while 68% of maculae were fluid free at study completion. Eighty seven percent of treated eyes developed nascent GA, of which in 74% of eyes was involving the fovea.<br><br>DISCUSSION: Despite initial improvement in mean BCVA, the improvement in BCVA was not maintained despite good overall control of the MNV3 lesions. The loss of BCVA was most likely due to the majority of eyes developing centre involving macular atrophy.},
}
@article {pmid38304609,
year = {2024},
author = {Guymer, R and Bailey, C and Chaikitmongkol, V and Chakravarthy, U and Chaudhary, V and Finger, RP and Gallego-Pinazo, R and Chuan, AKH and Ishida, S and Lövestam-Adrian, M and Parravano, M and Luna Pinto, JD and Schmitz-Valckenberg, S and Sheth, V and Souied, EH and Chi, GC and Gilberg, F and Glittenberg, C and Scheidl, S and Bengus, M},
title = {Rationale and Design of VOYAGER: Long-term Outcomes of Faricimab and Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Clinical Practice.},
journal = {Ophthalmology science},
volume = {4},
number = {3},
pages = {100442},
pmid = {38304609},
issn = {2666-9145},
abstract = {PURPOSE: To describe the rationale and design of the VOYAGER (NCT05476926) study, which aims to investigate the safety and effectiveness of faricimab and the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in clinical practice. VOYAGER also aims to understand drivers of clinical practice treatment outcomes by gaining novel insight into the intersection of treatment regimens, decisions, anatomic outcomes, and vision.<br><br>DESIGN: Primary data collection, noninterventional, prospective, multinational, multicenter clinical practice study.<br><br>PARTICIPANTS: At least 5000 patients initiating/continuing faricimab or PDS for nAMD/DME (500 sites, 31 countries).<br><br>METHODS: Management will be per usual care, with no mandated scheduled visits/imaging protocol requirements. Using robust methodologies, relevant clinical and ophthalmic data, including visual acuity (VA), and data on treatment clinical setting/regimens/philosophies, presence of anatomic features, and safety events will be collected. Routinely collected fundus images will be uploaded to the proprietary Imaging Platform for analysis. An innovative investigator interface will graphically display the patient treatment journey with the aim of optimizing treatment decisions.<br><br>MAIN OUTCOME MEASURES: Primary end point: VA change from baseline at 12 months per study cohort (faricimab in nAMD and in DME, PDS in nAMD). Secondary end points: VA change over time and per treatment regimens (fixed, treat-and-extend, pro re nata, and other) and number. Exploratory end points: VA change in relation to presence/location of anatomic features that impact vision (fluid, central subfield thickness, fibrosis, atrophy, subretinal hyperreflective material, diabetic retinopathy severity, and disorganization of retinal inner layers) and per treatment regimen/philosophies. The impact of regional and practice differences on outcomes will be assessed as will safety.<br><br>RESULTS: Recruitment commenced in November 2022 and will continue until late 2027, allowing for up to 5 years follow-up. Exploratory interim analyses are planned annually.<br><br>CONCLUSIONS: VOYAGER is an innovative study of retinal diseases that will assess the effectiveness and safety of faricimab and PDS in nAMD and DME and identify clinician- and disease-related factors driving treatment outcomes in clinical practices globally to help optimize vision outcomes.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38304607,
year = {2024},
author = {Jabs, DA and Schneider, MF and Pak, JW and Beck-Engeser, G and Chan, F and Ambayec, GC and Hunt, PW},
title = {Association of Intermediate-Stage Age-Related Macular Degeneration with Plasma Inflammatory Biomarkers in Persons with AIDS.},
journal = {Ophthalmology science},
volume = {4},
number = {3},
pages = {100437},
pmid = {38304607},
issn = {2666-9145},
support = {R01 EY025093/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To evaluate associations of plasma levels of inflammatory biomarkers with age-related macular degeneration (AMD) and cataract in persons with AIDS.<br><br>DESIGN: Nested case-control study (analysis 1) and nested cohort study (analysis 2).<br><br>PARTICIPANTS: Analysis 1: persons with AIDS and incident intermediate-stage AMD (n&#xa0;= 26) and controls without AMD matched for age, race/ethnicity, and gender (n&#xa0;= 49) from The Longitudinal Study of Ocular Complications of AIDS. Analysis 2: 475 persons from LSOCA with baseline plasma biomarker levels followed prospectively for cataract.<br><br>METHODS: In both analyses, cryopreserved plasma specimens obtained at baseline were assayed for monocyte chemoattractant protein (MCP)-1 (CC motif chemokine ligand [CCL] 2), macrophage inflammatory protein (MIP)-1&#x3b2; (CCL4), soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, and fractalkine (CX3 motif chemokine ligand 1 [CX3CL1]).<br><br>MAIN OUTCOME MEASURES: Analysis 1: mean difference (cases&#xa0;- controls) in plasma biomarker levels. Analysis 2: incident cataract.<br><br>RESULTS: After adjusting for plasma human immunodeficiency virus RNA level, CD4+ T-cell count, and smoking, elevated baseline plasma levels of sTNFR2 and IL-18 (mean differences [cases&#xa0;- controls] 0.11 log10[pg/mL]; 95% confidence interval [CI], 0.01-0.20; P&#xa0;= 0.024 and 0.13 log10[pg/mL]; 95% CI, 0.01-0.24; P&#xa0;= 0.037, respectively) each were associated with incident AMD. In a competing risk (with mortality) analysis, elevated baseline standardized log10 plasma levels of MCP-1, sTNFR2, IL-18, and fractalkine each were associated with a decreased cataract risk.<br><br>CONCLUSIONS: When combined with previous data suggesting that AMD is associated with elevated plasma levels of C-reactive protein, soluble CD14, and possibly IL-6, the association of elevated plasma levels of sTNFR2 and IL-18 with incident AMD, but not with incident cataract, suggests that innate immune system activation, and possibly NLRP3 inflammasome activation, may play a role in the pathogenesis of AMD in this population.<br><br>FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid38302908,
year = {2024},
author = {Skevas, C and de Olaguer, NP and Lleó, A and Thiwa, D and Schroeter, U and Lopes, IV and Mautone, L and Linke, SJ and Spitzer, MS and Yap, D and Xiao, D},
title = {Implementing and evaluating a fully functional AI-enabled model for chronic eye disease screening in a real clinical environment.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {51},
pmid = {38302908},
issn = {1471-2415},
mesh = {Humans ; Artificial Intelligence ; *Diabetic Retinopathy/diagnosis ; Mass Screening/methods ; Software ; *Macular Degeneration/diagnosis ; *Glaucoma/diagnosis ; },
abstract = {BACKGROUND: Artificial intelligence (AI) has the potential to increase the affordability and accessibility of eye disease screening, especially with the recent approval of AI-based diabetic retinopathy (DR) screening programs in several countries.<br><br>METHODS: This study investigated the performance, feasibility, and user experience of a seamless hardware and software solution for screening chronic eye diseases in a real-world clinical environment in Germany. The solution integrated AI grading for DR, age-related macular degeneration (AMD), and glaucoma, along with specialist auditing and patient referral decision. The study comprised several components: (1) evaluating the entire system solution from recruitment to eye image capture and AI grading for DR, AMD, and glaucoma; (2) comparing specialist's grading results with AI grading results; (3) gathering user feedback on the solution.<br><br>RESULTS: A total of 231 patients were recruited, and their consent forms were obtained. The sensitivity, specificity, and area under the curve for DR grading were 100.00%, 80.10%, and 90.00%, respectively. For AMD grading, the values were 90.91%, 78.79%, and 85.00%, and for glaucoma grading, the values were 93.26%, 76.76%, and 85.00%. The analysis of all false positive cases across the three diseases and their comparison with the final referral decisions revealed that only 17 patients were falsely referred among the 231 patients. The efficacy analysis of the system demonstrated the effectiveness of the AI grading process in the study's testing environment. Clinical staff involved in using the system provided positive feedback on the disease screening process, particularly praising the seamless workflow from patient registration to image transmission and obtaining the final result. Results from a questionnaire completed by 12 participants indicated that most found the system easy, quick, and highly satisfactory. The study also revealed room for improvement in the AMD model, suggesting the need to enhance its training data. Furthermore, the performance of the glaucoma model grading could be improved by incorporating additional measures such as intraocular pressure.<br><br>CONCLUSIONS: The implementation of the AI-based approach for screening three chronic eye diseases proved effective in real-world settings, earning positive feedback on the usability of the integrated platform from both the screening staff and auditors. The auditing function has proven valuable for obtaining efficient second opinions from experts, pointing to its potential for enhancing remote screening capabilities.<br><br>TRIAL REGISTRATION: Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der &#xc4;rztekammer Hamburg): 2021-10574-BO-ff.},
}
@article {pmid38300646,
year = {2024},
author = {Rajala, RVS and Rajala, A},
title = {From Insight to Eyesight: Unveiling the Secrets of the Insulin-Like Growth Factor Axis in Retinal Health.},
journal = {Aging and disease},
volume = {15},
number = {5},
pages = {1994-2002},
pmid = {38300646},
issn = {2152-5250},
support = {P30 EY021725/EY/NEI NIH HHS/United States ; R01 EY000871/EY/NEI NIH HHS/United States ; R01 EY030024/EY/NEI NIH HHS/United States ; R01 EY035282/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Insulin-Like Growth Factor I/metabolism ; *Receptor, IGF Type 1/metabolism ; *Signal Transduction ; Animals ; Retina/metabolism ; Retinal Pigment Epithelium/metabolism ; Macular Degeneration/metabolism/pathology ; Retinal Diseases/metabolism ; Insulin-Like Peptides ; },
abstract = {Insulin-like growth factor-1 (IGF-1) plays a diverse role in the retina, exerting its effects in both normal and diseased conditions. Deficiency of IGF-1 in humans leads to issues such as microcephaly, mental retardation, deafness, and postnatal growth failure. IGF-1 is produced in the retinal pigment epithelium (RPE) and activates the IGF-1 receptor (IGF-1R) in photoreceptor cells. When IGF-1R is absent in rod cells, it results in the degeneration of photoreceptors, emphasizing the neuroprotective function of IGF signaling in these cells. Contrastingly, in neovascular age-related macular degeneration (AMD), there is an overexpression of both IGF-1 and IGF-1R in RPE. The mechanisms behind this altered regulation of IGF-1 in diseased states are currently unknown. This comprehensive review provides recent insights into the role of IGF-1 in the health and disease of the retina, raising several unanswered questions that still need further investigation.},
}
@article {pmid38300559,
year = {2024},
author = {Fasih-Ahmad, S and Wang, Z and Mishra, Z and Vatanatham, C and Clark, ME and Swain, TA and Curcio, CA and Owsley, C and Sadda, SR and Hu, ZJ},
title = {Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {2},
pages = {1},
pmid = {38300559},
issn = {1552-5783},
support = {R01 EY029595/EY/NEI NIH HHS/United States ; R21 EY030619/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/diagnosis ; Retina ; *Macula Lutea ; Fovea Centralis ; Biomarkers ; Nonoxynol ; },
abstract = {PURPOSE: Lack of valid end points impedes developing therapeutic strategies for early age-related macular degeneration (AMD). Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The relationship between RMDA and the status of outer retinal bands on optical coherence tomography (OCT) have not been well defined. This study aims to characterize these relationships in early and intermediate AMD.<br><br>METHODS: Baseline data from 476 participants was assessed including eyes with early AMD (n&#xa0;=&#xa0;138), intermediate AMD (n&#xa0;=&#xa0;101), and normal aging (n&#xa0;=&#xa0;237). Participants underwent volume OCT imaging of the macula and rod intercept time (RIT) was measured. The ellipsoid zone (EZ) and interdigitation zone (IZ) on all OCT B-scans of the volumes were segmented. The area of detectable EZ and IZ, and mean thickness of IZ within the Early Treatment Diabetic Retinopathy Study (ETDRS) grid were computed and associations with RIT were assessed by Spearman's correlation coefficient and age adjusted.<br><br>RESULTS: Delayed RMDA (longer RIT) was most strongly associated with less preserved IZ area (r&#xa0;=&#xa0;-0.591; P&#xa0;<&#xa0;0.001), followed by decreased IZ thickness (r&#xa0;=&#xa0;-0.434; P&#xa0;<&#xa0;0.001), and EZ area (r&#xa0;=&#xa0;-0.334; P&#xa0;<&#xa0;0.001). This correlation between RIT and IZ integrity was not apparent when considering normal eyes alone within 1.5 mm of the fovea.<br><br>CONCLUSIONS: RMDA is correlated with the status of outer retinal bands in early and intermediate AMD eyes, particularly, the status of the IZ. This correlation is consistent with a previous analysis of only foveal B-scans and is biologically plausible given that retinoid availability, involving transfer at the interface attributed to the IZ, is rate-limiting for RMDA.},
}
@article {pmid38300334,
year = {2024},
author = {Manafi, N and Mahmoudi, A and Emamverdi, M and Corradetti, G and Corona, ST and Wykoff, CC and Sadda, SR},
title = {Topographic analysis of local OCT biomarkers which predict progression to atrophy in age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {7},
pages = {2083-2091},
pmid = {38300334},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Disease Progression ; Male ; Female ; *Retinal Pigment Epithelium/pathology ; Aged ; *Geographic Atrophy/diagnosis ; *Fluorescein Angiography/methods ; Case-Control Studies ; Follow-Up Studies ; Fundus Oculi ; Visual Acuity ; Biomarkers/metabolism ; Aged, 80 and over ; Atrophy ; Retinal Drusen/diagnosis/metabolism/etiology ; },
abstract = {PURPOSE: To define optical coherence tomography (OCT) biomarkers that precede the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) at that location in eyes with age-related macular degeneration (AMD).<br><br>METHODS: In this retrospective case-control study, patients with dry AMD who had evidence of cRORA and OCT data available for 4&#xa0;years (48&#x2009;&#xb1;&#x2009;4&#xa0;months) prior to the first visit with evidence of cRORA were included. The visit 4&#xa0;years prior to the development of cRORA was defined as the baseline visit, and the region on the OCT B-scans of future cRORA development was termed the case region. A region in the same eye at the same distance from the foveal center as the case region that did not progress to cRORA was selected as the control region. OCT B-scans at the baseline visit through both the case and control regions were evaluated for the presence of soft and cuticular drusen, drusen with hyporeflective cores (hcD), drusenoid pigment epithelial detachments (PED), subretinal drusenoid deposits (SDD), thick and thin double-layer signs (DLS), intraretinal hyperreflective foci (IHRF), and acquired vitelliform lesions (AVL).<br><br>RESULTS: A total of 57 eyes of 41 patients with dry AMD and evidence of cRORA were included. Mean time from the baseline visit to the first visit with cRORA was 44.7 &#xb1; 6.5&#xa0;months. The presence of soft drusen, drusenoid PED, AVL, thin DLS, and IHRF at the baseline visit was all associated with a significantly increased risk of cRORA at that location. Multivariable logistic regression revealed that IHRF (OR, 8.559; p&#x2009;<&#x2009;0.001), drusenoid PED (OR, 7.148; p&#x2009;=&#x2009;0.001), and a thin DLS (OR, 3.483; p&#x2009;=&#x2009;0.021) were independent predictors of development of cRORA at that location.<br><br>CONCLUSIONS: IHRF, drusenoid PED, and thin DLS are all local risk factors for the development of cRORA at that same location. These findings would support the inclusion of these features within a more granular staging system defining specific steps in the progression from early AMD to atrophy.},
}
@article {pmid38299764,
year = {2024},
author = {Bisen, AC and Agrawal, S and Rayiti, R and Sanap, SN and Biswas, A and Mishra, A and Gupta, NM and Bhatta, RS},
title = {Pirfenidone: A Promising Drug in Ocular Therapeutics.},
journal = {Chemistry &amp; biodiversity},
volume = {21},
number = {3},
pages = {e202301389},
doi = {10.1002/cbdv.202301389},
pmid = {38299764},
issn = {1612-1880},
support = {//Indian Council of Medical Research, New Delhi, India/ ; },
mesh = {*Wound Healing ; *Pyridones/pharmacology/therapeutic use ; },
abstract = {Pirfenidone, initially indicated for lung fibrosis, has gone beyond its original purpose, and shown promise in eye care. This detailed review tracks its evolution from lung treatment to aiding eye healing as evidenced by published literature. Pirfenidone's multifaceted attributes extend to mitigating corneal fibrosis, inflammation, and trauma. Through rigorous investigations, its efficacy emerges in diabetic retinopathy, macular degeneration, and postoperative glaucoma interventions. As an unheralded protagonist, pirfenidone reshapes ocular care paradigms, inviting renewed research opportunities.},
}
@article {pmid38299009,
year = {2024},
author = {Wang, X and Fang, J and Yang, L},
title = {Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons.},
journal = {Open life sciences},
volume = {19},
number = {1},
pages = {20220773},
pmid = {38299009},
issn = {2391-5412},
abstract = {The purpose of this study was to explore the related research progress of ocular complications (OCs) caused by type 2 diabetes mellitus (T2DM), tear and tarsal function, and the application of deep learning (DL) in the diagnosis of diabetes and OCs caused by it, to provide reference for the prevention and control of OCs in T2DM patients. This study reviewed the pathogenesis and treatment of diabetes retinopathy, keratopathy, dry eye disease, glaucoma, and cataract, analyzed the relationship between OCs and tear function and tarsal function, and discussed the application value of DL in the diagnosis of diabetes and OCs. Diabetes retinopathy is related to hyperglycemia, angiogenic factors, oxidative stress, hypertension, hyperlipidemia, and other factors. The increase in water content in the corneal stroma leads to corneal relaxation, loss of transparency, and elasticity, and can lead to the occurrence of corneal lesions. Dry eye syndrome is related to abnormal stability of the tear film and imbalance in neural and immune regulation. Elevated intraocular pressure, inflammatory reactions, atrophy of the optic nerve head, and damage to optic nerve fibers are the causes of glaucoma. Cataract is a common eye disease in the elderly, which is a visual disorder caused by lens opacity. Oxidative stress is an important factor in the occurrence of cataracts. In clinical practice, blood sugar control, laser therapy, and drug therapy are used to control the above eye complications. The function of tear and tarsal plate will be affected by eye diseases. Retinopathy and dry eye disease caused by diabetes will cause dysfunction of tear and tarsal plate, which will affect the eye function of patients. Furthermore, DL can automatically diagnose and classify eye diseases, automatically analyze fundus images, and accurately diagnose diabetes retinopathy, macular degeneration, and other diseases by analyzing and processing eye images and data. The treatment of T2DM is difficult and prone to OCs, which seriously threatens the normal life of patients. The occurrence of OCs is closely related to abnormal tear and tarsal function. Based on DL, clinical diagnosis and treatment of diabetes and its OCs can be carried out, which has positive application value.},
}
@article {pmid38297419,
year = {2024},
author = {Erdinest, N and Ben Ephraim Noyman, D and Lavy, I and Berkow, D and Pincovich, S and London, N and Shmueli, O and Levinger, N and Morad, Y and Landau, D and Levi Vineberg, T},
title = {[ARTIFICIAL INTELLIGENCE IN OPHTHALMOLOGY].},
journal = {Harefuah},
volume = {163},
number = {1},
pages = {37-42},
pmid = {38297419},
issn = {0017-7768},
mesh = {Infant, Newborn ; Humans ; Artificial Intelligence ; *Ophthalmology ; Algorithms ; Machine Learning ; *Glaucoma ; },
abstract = {Artificial intelligence (AI) was first introduced in 1956, and effectively represents the fourth industrial revolution in human history. Over time, this medium has evolved to be the preferred method of medical imagery interpretation. Today, the implementation of AI in the medical field as a whole, and the ophthalmological field in particular, is diverse and includes diagnose, follow-up and monitoring of the progression of ocular diseases. For example, AI algorithms can identify ectasia, and pre-clinical signs of keratoconus, using images and information computed from various corneal maps. Machine learning (ML) is a specific technique for implementing AI. It is defined as a series of automated methods that identify patterns and templates in data and leverage these to perform predictions on new data. This technology was first applied in the 1980s. Deep learning is an advanced form of ML inspired by and designed to imitate the human brain process, constructed of layers, each responsible for identifying patterns, thereby successfully modeling complex scenarios. The significant advantage of ML in medicine is in its' ability to monitor and follow patients with efficiency at a low cost. Deep learning is utilized to monitor ocular diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, cataract, and retinopathy of prematurity. These conditions, as well as others, require frequent follow-up in order to track changes over time. Though computer technology is important for identifying and grading various ocular diseases, it still necessitates additional clinical validation and does not entirely replace human diagnostic skill.},
}
@article {pmid38297400,
year = {2024},
author = {Song, YY and Seong, HJ and Kim, JT and Lee, SC and Lee, MW},
title = {Features of optical coherence tomography angiography in age-related macular degeneration with residual fluid after three loading doses of aflibercept.},
journal = {Eye and vision (London, England)},
volume = {11},
number = {1},
pages = {4},
pmid = {38297400},
issn = {2326-0254},
abstract = {BACKGROUND: To identify the macular neovascularization (MNV) features in exudative age-related macular degeneration (AMD) patients who exhibited residual fluid after receiving three loading doses of aflibercept.<br><br>METHODS: Patients were classified into two groups: Group 1, which did not exhibit intraretinal fluid (IRF) and subretinal fluid (SRF), and Group 2, which did exhibit IRF and/or SRF. Optical coherence tomography angiography (OCTA) features were assessed and compared between the groups.<br><br>RESULTS: A total of 101 eyes were enrolled; 65 for Group 1 and 36 for Group 2. No significant differences were found in baseline MNV size (2.94&#x2009;&#xb1;&#x2009;2.51&#xa0;&#xb5;m[2] vs. 2.22&#x2009;&#xb1;&#x2009;2.26 &#xb5;m[2], P&#x2009;=&#x2009;0.178) or vessel density (47.1&#x2009;&#xb1;&#x2009;15.4&#xa0;% vs. 41.3&#x2009;&#xb1;&#x2009;10.5%, P&#x2009;=&#x2009;0.052) between Groups 1 and 2. There were significant differences in the presence of loops (52.3% vs. 75%, P&#x2009;=&#x2009;0.026) and peripheral arcades (29.2% vs. 55.6%, P&#x2009;<&#x2009;0.001) at baseline between the two groups. In Group 1, there was a significant reduction in the presence of branching (P&#x2009;<&#x2009;0.001) and loops (P&#x2009;=&#x2009;0.016) after treatment. In Group 2, only the presence of branching decreased significantly (P&#x2009;<&#x2009;0.001) after treatment. Multivariable analysis revealed that the presence of a peripheral arcade (B&#x2009;=&#x2009;4.77, P&#x2009;=&#x2009;0.001) was significantly associated with residual fluid.<br><br>CONCLUSIONS: Although responding to treatment, the presence of loops and peripheral arcades in exudative AMD patients may contribute to residual fluid following the three loading doses of aflibercept. The peripheral arcade, in particular, may play a more significant role in the presence of residual fluid.},
}
@article {pmid38295331,
year = {2024},
author = {Kráľová, J&#x160; and Kolář, P and Kapounová, Z and Veselý, P and Brázdová, ZD},
title = {Lifestyle factors associated with age-related macular degeneration: Case-control study.},
journal = {European journal of ophthalmology},
volume = {34},
number = {5},
pages = {1548-1554},
doi = {10.1177/11206721241229310},
pmid = {38295331},
issn = {1724-6016},
mesh = {Humans ; Male ; Female ; Aged ; Case-Control Studies ; Risk Factors ; Cross-Sectional Studies ; *Life Style ; *Macular Degeneration/epidemiology/etiology ; *Tomography, Optical Coherence ; Surveys and Questionnaires ; Aged, 80 and over ; Czech Republic/epidemiology ; Middle Aged ; Tobacco Smoke Pollution/adverse effects ; Smoking/adverse effects/epidemiology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss in individuals aged ≥ 65 years in developed countries. This study aimed to determine the associations between modifiable risk factors and AMD. This is the first study describing the relationship between lifestyle factors and AMD in the Czech Republic.<br><br>METHODS: In this cross-sectional case-control study, 93 AMD cases and 58 controls without AMD and cataract were included. All participants were examined by Optical coherence tomography at the Clinic of Eye Treatment at the University Hospital Brno. Data were collected using a pre-tested self-report questionnaire in a face-to-face interview.<br><br>RESULTS: We found significant associations between those who were living in the city (OR 95% CI: 2.19 (1.0-4.6); p&#x2009;=&#x2009;0,039), with a positive family history of AMD (OR 95% CI: 12.75 (1.6-98.6); p&#x2009;=&#x2009;0,015), exposure to cigarette smoke (OR 95% CI: 2.72 (1.4-5.4); p&#x2009;=&#x2009;0,004), and daily exposure to passive smoking (OR 95% CI: 2.29 (1.0-5.1); p&#x2009;=&#x2009;0,045) and AMD. In men, we found significant associations between daily sunlight exposure (OR 95% CI: 2.98 (1.0-8.5); p&#x2009;=&#x2009;0,041), short or long sleep duration (OR 95% CI: 3.98 (1.2-13.2); p&#x2009;=&#x2009;0,024) and AMD. Men daily exposed to sunlight were at a 2.98 times higher risk of AMD than men with less than daily sunlight exposure. Men with short or long sleep duration (< 6 and&#x2009;>&#x2009;8&#x2005;h) were at a 3.98 times higher risk of AMD than men with recommended sleep duration of 6-8&#x2005;h.<br><br>CONCLUSIONS: An increased risk of AMD was observed for living in the city, family history of AMD, exposure to cigarette smoke, and daily exposure to passive smoking. Increased risk of AMD was observed for daily sunlight exposure and short or long sleep duration; however, only in men.},
}
@article {pmid38293586,
year = {2024},
author = {Kitahata, S and Mandai, M and Ichikawa, H and Tanaka, Y and Senba, T and Kajita, K and Sugita, S and Kadonosono, K and Takahashi, M},
title = {Investigation of the effectiveness of gelatin hydrolysate in human iPS-RPE cell suspension transplantation.},
journal = {Regenerative therapy},
volume = {25},
number = {},
pages = {238-249},
pmid = {38293586},
issn = {2352-3204},
abstract = {INTRODUCTION: The retinal pigment epithelium (RPE) plays essential roles in maintaining retinal functions as well as choroidal capillaries and can lead to visual disorders if dysfunctional. Transplantation of human-induced pluripotent stem cell-derived RPE (hiPSC-RPE) is a promising therapy for such RPE impaired conditions including age-related macular degeneration. The challenge with cell suspension transplantation is targeted delivery of graft cells and undesired cell reflux. Gelatin hydrolysate, a soluble variant with specific molecular weight distribution, is examined in this study for its potential use in hiPSC-RPE suspension transplantation, particularly in reducing cell reflux and enhancing RPE engraftment.<br><br>METHODS: A retinal bleb model was created using polydimethylsiloxane (PDMS) soft lithography to quantify cellular reflux. We examined the effects of gelatin hydrolysate on the hiPSC-RPE of various aspects of cell behavior and performance such as cell viability, hypoxia reaction, morphology, induction of inflammation and immune responses.<br><br>RESULTS: Gelatin hydrolysate at 5&#xa0;% concentration effectively mitigated cell reflux in&#xa0;vitro mimic, improved cell viability, reduced cell aggregation, and had an inhibitory effect on hypoxic reactions due to cell deposition with hiPSC-RPE. Additionally, gelatin hydrolysate did not affect cell adhesion and morphology, and decreased the expression of major histocompatibility complex class II molecules, which suggests reduced immunogenicity of hiPSC-RPE.<br><br>CONCLUSION: Gelatin hydrolysate is considered a valuable and useful candidate for future regenerative therapies in hiPSC-RPE suspension transplantation.},
}
@article {pmid38291368,
year = {2024},
author = {Wickman, I and Lövestam-Adrian, M and Granstam, E and Kjellström, U and Schroeder, M},
title = {The impact of COVID-19 on aflibercept treatment of neovascular AMD in Sweden - data from the Swedish Macula Register.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {49},
pmid = {38291368},
issn = {1471-2415},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab ; Sweden/epidemiology ; Pandemics ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; Visual Acuity ; *COVID-19/epidemiology ; *Wet Macular Degeneration/drug therapy/epidemiology ; Retrospective Studies ; Treatment Outcome ; *Recombinant Fusion Proteins ; *Receptors, Vascular Endothelial Growth Factor ; },
abstract = {BACKGROUND: The purpose of the study was to compare the real-world aflibercept treatment and visual outcomes, and to examine the adherence to pandemic guidelines in two groups of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) before and during the first year of the COVID-19 pandemic in Sweden up to the 1-year follow-up.<br><br>METHODS: This is a retrospective observational study including 2915 treatment na&#xef;ve eyes with nAMD. Using data from the Swedish Macula Register (SMR), 1597 eyes initiating treatment between 1 July 2018 and 31 January 2019 (pre-pandemic group) were compared with 1318 eyes starting treatment between 1 February and 31 August 2020 (pandemic group). The eyes were then followed for 1 year&#x2009;&#xb1;&#x2009;2 months, hence the first group was unaffected by the pandemic while the second group was affected. The focus was on baseline characteristics, visual acuity (VA) change from baseline, number of injections, treatment regimen, number of appointments and the frequency and length of appointment delays. The Wilcoxon Signed-Rank Test was used to compare baseline VA to follow-up VA within the respective groups. The Mann-Whitney U-test and Fisher's exact test were used to compare outcomes between the groups.<br><br>RESULTS: Baseline characteristics were similar between the two groups. The percentage of eyes with an available follow-up VA after 1 year was 58% in the pre-pandemic group vs. 44% in the pandemic group. VA in the pre-pandemic group had increased significantly after 1 year, from 62.2&#x2009;&#xb1;&#x2009;14.1 letters to 64.8&#x2009;&#xb1;&#x2009;16.1 letters (n&#x2009;=&#x2009;921); p&#x2009;<&#x2009;0.0001. In the pandemic group, VA increased from 61.1&#x2009;&#xb1;&#x2009;15.8 to 64.9&#x2009;&#xb1;&#x2009;16.9 (n&#x2009;=&#x2009;575); p&#x2009;<&#x2009;0.0001. There was no significant difference in mean VA change between the groups; p&#x2009;=&#x2009;0.1734. The pre-pandemic group had significantly more delays than the pandemic group, 45% vs. 36%; p&#x2009;<&#x2009;0.0001.<br><br>CONCLUSIONS: The pre-pandemic and pandemic groups had similar VA gains at 1-year follow-up, but with a reduced number of available VA in the pandemic group. Clinics were able to implement and prioritize injection visits excluding VA measurements, helping to reduce delays and maintain VA gains during the COVID-19 pandemic.},
}
@article {pmid38291120,
year = {2024},
author = {Inoda, S and Takahashi, H and Takahashi, R and Hashimoto, Y and Yoshida, H and Tsukii, R and Takahashi, H and Kawashima, H and Yanagi, Y},
title = {One-year outcome of brolucizumab for neovascular age-related macular degeneration in Japanese patients.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {2451},
pmid = {38291120},
issn = {2045-2322},
mesh = {Humans ; Japan/epidemiology ; Retrospective Studies ; Inflammation ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor ; *Antibodies, Monoclonal, Humanized ; },
abstract = {A new anti-vascular endothelial growth factor agent, brolucizumab, was approved by the United States Food and Drug Administration in 2019. We evaluated whether brolucizumab reduces the treatment burden of neovascular age-related macular degeneration (nAMD) after switching by examining 1-year treatment outcomes in a real-world setting. This retrospective single-institution study included 107 consecutive eyes with nAMD treated with brolucizumab. Among these eyes, 30 with treatment-naïve nAMD and 77 treated with other anti-VEGF agents for more than a year were included. All eyes were managed using a treat and extend (TAE) or modified TAE regimen. The last injection intervals at 52 weeks were 12.9 and 12.1 weeks in the treatment-naïve and switch therapy groups, respectively. Among switch therapy group patients whose pre-switch injection intervals were shorter than 120 days (n = 62 eyes), the injection interval was significantly longer after the switch than before, with a mean difference of 2.7 weeks (P < 0.0001). Intraocular inflammation events occurred in 2 and 7 treatment-naïve and switch therapy patients, respectively. In conclusion, brolucizumab might reduce the treatment burden in patients who required the injection of other anti-VEGF agents with a 120-day interval or shorter, despite a relatively high discontinuation rate due to intraocular inflammation.},
}
@article {pmid38291069,
year = {2024},
author = {Yen, WT and Wu, CS and Yang, CH and Chen, YH and Lee, CH and Hsu, CR},
title = {Efficacy and safety of intravitreal faricimab for neovascular age-related macular degeneration: a systematic review and meta-analysis.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {2485},
pmid = {38291069},
issn = {2045-2322},
mesh = {Humans ; Angiogenesis Inhibitors/adverse effects ; *Antibodies, Bispecific/adverse effects ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; },
abstract = {We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).},
}
@article {pmid38290804,
year = {2024},
author = {Vujosevic, S and Loewenstein, A and O'Toole, L and Schmidt-Erfurth, UM and Zur, D and Chakravarthy, U},
title = {Imaging geographic atrophy: integrating structure and function to better understand the effects of new treatments.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {6},
pages = {773-778},
doi = {10.1136/bjo-2023-324246},
pmid = {38290804},
issn = {1468-2079},
mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/diagnostic imaging ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Retinal Pigment Epithelium/pathology/diagnostic imaging/physiopathology ; Fluorescein Angiography/methods ; Visual Field Tests ; },
abstract = {Geographic atrophy (GA) is an advanced and irreversible form of age-related macular degeneration (AMD). Chronic low grade inflammation is thought to act as an initiator of this degenerative process, resulting in loss of photoreceptors (PRs), retinal pigment epithelium (RPE) and the underlying choriocapillaris. This review examined the challenges of clinical trials to date which have sought to treat GA, with particular reference to the successful outcome of C3 complement inhibition. Currently, optical coherence tomography (OCT) seems to be the most suitable method to detect GA and monitor the effect of treatment. In addition, the merits of using novel anatomical endpoints in detecting GA expansion are discussed. Although best-corrected visual acuity is commonly used to monitor disease in GA, other tests to determine visual function are explored. Although not widely available, microperimetry enables quantification of retinal sensitivity (RS) and macular fixation behaviour related to fundus characteristics. There is a spatial correlation between OCT/fundus autofluorescence evaluation of PR damage outside the area of RPE loss and RS on microperimetry, showing important associations with visual function. Standardisation of testing by microperimetry is necessary to enable this modality to detect AMD progression. Artificial intelligence (AI) analysis has shown PR layers integrity precedes and exceeds GA loss. Loss of the ellipsoid zone has been recognised as a primary outcome parameter in therapeutic trials for GA. The integrity of the PR layers imaged by OCT at baseline has been shown to be an important prognostic indicator. AI has the potential to be invaluable in personalising care and justifying treatment intervention.},
}
@article {pmid38289615,
year = {2024},
author = {Ricardi, F and Borrelli, E and Boscia, G and Gelormini, F and Marica, V and Conte, F and Viggiano, P and Marolo, P and Bandello, F and Reibaldi, M},
title = {Relationship of Topographic Distribution of Macular Atrophy Secondary to Neovascular AMD and Reading Performance.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {1},
pages = {44},
pmid = {38289615},
issn = {1552-5783},
mesh = {Humans ; Angiogenesis Inhibitors ; Reading ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/complications/diagnosis ; *Diabetic Retinopathy ; Fovea Centralis ; Atrophy ; },
abstract = {PURPOSE: The purpose of this study was to provide a topographical assessment of macular atrophy in successfully treated neovascular age-related macular degeneration (AMD) eyes to investigate determinants of monocular reading performance.<br><br>METHODS: A total of 60 participants (60 eyes) with previously treated neovascular AMD and absence of optical coherence tomography (OCT) signs of exudation were enrolled. Reading performance was assessed monocularly using Radner charts. The following variables were obtained: (i) the reading acuity was defined as the logarithm of the reading acuity determination (LogRAD), at the smallest sentence, a patient is able to read in less than 30 seconds; (ii) the maximum reading speed was defined as the fastest time achieved and is calculated in words per minute (wpm). OCT images were reviewed for the presence of macular atrophy within the central, 4 inner and 4 outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid subfields. Contributory factors affecting reading performance were examined using univariable and multivariable linear mixed model considering reading acuity and reading speed as dependent variables.<br><br>RESULTS: Median (interquartile range [IQR]) values were 0.53 (IQR = 0.17) LogRAD for reading acuity, and 144 (60) wpm for maximum reading speed. Thirty-five out of 60 (58.3%) eyes were characterized by the presence of macular atrophy. In multiple regression analysis, reading acuity was significantly associated with presence of macular atrophy in the foveal central circle (P = 0.024). Conversely, the maximum reading speed was associated with presence of macular atrophy in the inner-right ETDRS subfield (P = 0.005).<br><br>CONCLUSIONS: We showed a significant relationship between presence and location of macular atrophy and reading performance in neovascular AMD.},
}
@article {pmid38289610,
year = {2024},
author = {Sil Kar, S and Cetin, H and Srivastava, SK and Madabhushi, A and Ehlers, JP},
title = {Texture-Based Radiomic SD-OCT Features Associated With Response to Anti-VEGF Therapy in a Phase III Neovascular AMD Clinical Trial.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {1},
pages = {29},
pmid = {38289610},
issn = {2164-2591},
support = {R01 CA216579/CA/NCI NIH HHS/United States ; C06 RR012463/RR/NCRR NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; U01 CA239055/CA/NCI NIH HHS/United States ; R01 CA268287/CA/NCI NIH HHS/United States ; R01 CA249992/CA/NCI NIH HHS/United States ; R01 CA202752/CA/NCI NIH HHS/United States ; R01 CA208236/CA/NCI NIH HHS/United States ; U01 CA248226/CA/NCI NIH HHS/United States ; I01 BX004121/BX/BLRD VA/United States ; R43 EB028736/EB/NIBIB NIH HHS/United States ; U01 CA269181/CA/NCI NIH HHS/United States ; R01 CA257612/CA/NCI NIH HHS/United States ; U54 CA254566/CA/NCI NIH HHS/United States ; R01 CA220581/CA/NCI NIH HHS/United States ; K23 EY022947/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Radiomics ; Retinal Pigment Epithelium ; *Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; *Wet Macular Degeneration/diagnostic imaging/drug therapy ; },
abstract = {PURPOSE: The goal of this study was to evaluate the role of texture-based baseline radiomic features (Fr) and dynamic radiomics alterations (delta, FΔr) within multiple targeted compartments on optical coherence tomography (OCT) scans to predict response to anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: HAWK is a phase 3 clinical trial data set of active nAMD patients (N = 1082) comparing brolucizumab and aflibercept. This analysis included patients receiving 6&#xa0;mg brolucizumab or 2&#xa0;mg aflibercept and categorized as complete responders (n = 280) and incomplete responders (n = 239) based on whether or not the eyes achieved/maintained fluid resolution on OCT. A total of 481 Fr were extracted from each of the fluid, subretinal hyperreflective material (SHRM), retinal tissue, and sub-retinal pigment epithelium (RPE) compartments. Most discriminating eight baseline features, selected by the minimum redundancy, maximum relevance feature selection, were evaluated using a quadratic discriminant analysis (QDA) classifier on the training set (Str, n = 363) to differentiate between the two patient groups. Classifier performance was subsequently validated on independent test set (St, n = 156).<br><br>RESULTS: In total, 519 participants were included in this analysis from the HAWK phase 3 study. There were 280 complete responders and 219 incomplete responders. Compartmental analysis of radiomics featured identified the sub-RPE and SHRM compartments as the most distinguishing between the two response groups. The QDA classifier yielded areas under the curve of 0.78, 0.79, and 0.84, respectively, using Fr, F&#x394;r, and combined Fr, F&#x394;r, and Fc on St.<br><br>CONCLUSIONS: Utilizing compartmental static and dynamic radiomics features, unique differences were identified between eyes that respond differently to anti-VEGF therapy in a large phase 3 trial that may provide important predictive value.<br><br>TRANSLATIONAL RELEVANCE: Imaging biomarkers, such as radiomics features identified in this analysis, for predicting treatment response are needed to enhanced precision medicine in the management of nAMD.},
}
@article {pmid38289348,
year = {2024},
author = {Yu, C and Lad, EM and Mathew, R and Shiraki, N and Littleton, S and Chen, Y and Hou, J and Schlepckow, K and Degan, S and Chew, L and Amason, J and Kalnitsky, J and Bowes Rickman, C and Proia, AD and Colonna, M and Haass, C and Saban, DR},
title = {Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and Trem2.},
journal = {The Journal of experimental medicine},
volume = {221},
number = {3},
pages = {},
pmid = {38289348},
issn = {1540-9538},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01EY030906/NH/NIH HHS/United States ; K23 EY026988/EY/NEI NIH HHS/United States ; R01 EY030906/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; R01 EY021798/EY/NEI NIH HHS/United States ; T32 GM007171/GM/NIGMS NIH HHS/United States ; },
mesh = {Aged ; Animals ; Humans ; Mice ; Atrophy ; *Galectin 3/genetics ; Macrophages ; *Membrane Glycoproteins/genetics ; Microglia ; *Receptors, Immunologic/genetics ; *Retinal Degeneration ; },
abstract = {Outer retinal degenerations, including age-related macular degeneration (AMD), are characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. In these blinding diseases, macrophages accumulate at atrophic sites, but their ontogeny and niche specialization remain poorly understood, especially in humans. We uncovered a unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and human AMD. In disease models, conditional deletion of galectin-3 in microglia led to phagocytosis defects and consequent augmented photoreceptor death, RPE damage, and vision loss, indicating protective roles. Mechanistically, Trem2 signaling orchestrated microglial migration to atrophic sites and induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection but in a galectin-3-dependent manner. In elderly human subjects, we identified this highly conserved microglial population that expressed galectin-3 and Trem2. This population was significantly enriched in the macular RPE-choroid of AMD subjects. Collectively, our findings reveal a neuroprotective population of microglia and a potential therapeutic target for mitigating retinal degeneration.},
}
@article {pmid38288111,
year = {2023},
author = {Laudenberg, N and Kinuthia, UM and Langmann, T},
title = {Microglia depletion/repopulation does not affect light-induced retinal degeneration in mice.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1345382},
pmid = {38288111},
issn = {1664-3224},
mesh = {Mice ; Animals ; *Retinal Degeneration/metabolism ; Microglia/metabolism ; Retina/pathology ; *Macular Degeneration/metabolism ; Inflammation/metabolism ; },
abstract = {Reactive microglia are a hallmark of age-related retinal degenerative diseases including age-related macular degeneration (AMD). These cells are capable of secreting neurotoxic substances that may aggravate inflammation that leads to loss of photoreceptors and impaired vision. Despite their role in driving detrimental inflammation, microglia also play supporting roles in the retina as they are a crucial cellular component of the regulatory innate immune system. In this study, we used the colony stimulating factor 1 receptor (CSF1R)-antagonist PLX3397 to investigate the effects of microglia depletion and repopulation in a mouse model of acute retinal degeneration that mimics some aspects of dry AMD. Our main goal was to investigate whether microglia depletion and repopulation affects the outcome of light-induced retinal degeneration. We found that microglia depletion effectively decreased the expression of several key pro-inflammatory factors but was unable to influence the extent of retinal degeneration as determined by optical coherence tomography (OCT) and histology. Interestingly, we found prominent cell debris accumulation in the outer retina under conditions of microglia depletion, presumably due to the lack of efficient phagocytosis that could not be compensated by the retinal pigment epithelium. Moreover, our in vivo experiments showed that renewal of retinal microglia by repopulation did also not prevent rapid microglia activation or preserve photoreceptor death under conditions of light damage. We conclude that microglia ablation strongly reduces the expression of pro-inflammatory factors but cannot prevent photoreceptor loss in the light-damage paradigm of retinal degeneration.},
}
@article {pmid38287062,
year = {2024},
author = {Abd El-Khalek, AA and Balaha, HM and Alghamdi, NS and Ghazal, M and Khalil, AT and Abo-Elsoud, MEA and El-Baz, A},
title = {A concentrated machine learning-based classification system for age-related macular degeneration (AMD) diagnosis using fundus images.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {2434},
pmid = {38287062},
issn = {2045-2322},
mesh = {Humans ; Aged ; Fundus Oculi ; Retina ; *Wet Macular Degeneration/diagnosis ; *Geographic Atrophy/diagnostic imaging ; Machine Learning ; },
abstract = {The increase in eye disorders among older individuals has raised concerns, necessitating early detection through regular eye examinations. Age-related macular degeneration (AMD), a prevalent condition in individuals over 45, is a leading cause of vision impairment in the elderly. This paper presents a comprehensive computer-aided diagnosis (CAD) framework to categorize fundus images into geographic atrophy (GA), intermediate AMD, normal, and wet AMD categories. This is crucial for early detection and precise diagnosis of age-related macular degeneration (AMD), enabling timely intervention and personalized treatment strategies. We have developed a novel system that extracts both local and global appearance markers from fundus images. These markers are obtained from the entire retina and iso-regions aligned with the optical disc. Applying weighted majority voting on the best classifiers improves performance, resulting in an accuracy of 96.85%, sensitivity of 93.72%, specificity of 97.89%, precision of 93.86%, F1 of 93.72%, ROC of 95.85%, balanced accuracy of 95.81%, and weighted sum of 95.38%. This system not only achieves high accuracy but also provides a detailed assessment of the severity of each retinal region. This approach ensures that the final diagnosis aligns with the physician's understanding of AMD, aiding them in ongoing treatment and follow-up for AMD patients.},
}
@article {pmid38286571,
year = {2024},
author = {Wu, Z and Terheyden, JH and Hodgson, LAB and Guymer, RH},
title = {Choroidal signal hypertransmission on optical coherence tomography imaging: Association with development of geographic atrophy in age-related macular degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {4},
pages = {431-439},
doi = {10.1111/ceo.14356},
pmid = {38286571},
issn = {1442-9071},
support = {#2008382//National Health and Medical Research Council/ ; APP1027624//National Health and Medical Research Council/ ; GNT1194667//National Health and Medical Research Council/ ; BM-AXIS program//Bundesministerium f&#xfc;r Bildung und Forschung/ ; //Macular Disease Foundation Australia/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Geographic Atrophy/diagnosis/etiology ; Female ; Male ; Aged ; *Choroid/diagnostic imaging/pathology ; Disease Progression ; Aged, 80 and over ; Macular Degeneration/diagnosis ; Fluorescein Angiography/methods ; Visual Acuity/physiology ; Retinal Drusen/diagnosis ; Follow-Up Studies ; Middle Aged ; Risk Factors ; Prospective Studies ; Incidence ; },
abstract = {BACKGROUND: To examine the association between large choroidal signal hypertransmission ≥250 μm (LHyperT) on optical coherence tomography (OCT) with the risk of developing geographic atrophy (GA) and compare this risk with those associated with nascent geographic atrophy (nGA).<br><br>METHODS: Two hundred and eighty eyes from 140 participants with bilateral large drusen and without late age-related macular degeneration (AMD) or nGA at baseline underwent OCT imaging and colour fundus photography (CFP) at 6-monthly intervals up to 5&#x2009;years. OCT scans were graded for the presence of LHyperT and nGA, and CFPs were graded for the presence of GA.<br><br>RESULTS: The five-year incidence of LHyperT and nGA were 37% and 27% respectively (p&#x2009;=&#x2009;0.003), and the two-year probability of their progression to GA were 17% and 40%, respectively (p&#x2009;=&#x2009;0.002). LHyperT and nGA explained 81% and 91% of the variance in the time to develop GA, respectively (p&#x2009;=&#x2009;0.032), and they were both associated with a significantly higher rate of GA development compared to eyes without these lesions (adjusted hazard ratio&#x2009;=&#x2009;110.8 and 183.2, respectively; p&#x2009;<&#x2009;0.001 for both).<br><br>CONCLUSIONS: LHyperT and nGA were both high-risk features for GA development, but the latter showed a higher rate of GA progression and explained a significantly greater proportion of the variance in the time to develop GA. As such, nGA may be a more robust surrogate endpoint than LHyperT for the conventional clinical endpoint of CFP-defined GA for intervention trials in the early stages of AMD.},
}
@article {pmid38285461,
year = {2024},
author = {Sonntag, SR and Klein, B and Brinkmann, R and Grisanti, S and Miura, Y},
title = {Fluorescence Lifetime Imaging Ophthalmoscopy of Mouse Models of Age-related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {13},
number = {1},
pages = {24},
pmid = {38285461},
issn = {2164-2591},
mesh = {Mice ; Animals ; *Antioxidants ; NF-E2-Related Factor 2 ; Mice, Knockout, ApoE ; Ophthalmoscopy ; *Macular Degeneration/genetics ; Disease Models, Animal ; Fundus Oculi ; Apolipoproteins E ; *Azo Compounds ; },
abstract = {PURPOSE: To investigate fluorescence lifetime of mouse models of age-related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).<br><br>METHODS: Two AMD mouse models, apolipoprotein E knockout (ApoE-/-) mice and NF-E2-related factor-2 knockout (Nrf2-/-) mice, and their wild-type mice underwent monthly ophthalmic examinations including FLIO from 3&#xa0;months of age. After euthanasia at the age of 6 or 11&#xa0;months, blood plasma was collected to determine total antioxidant capacity and eyes were enucleated for Oil red O (ORO) lipid staining of chorioretinal tissue.<br><br>RESULTS: In FLIO, the mean fluorescence lifetime (&#x3c4;m) of wild type shortened with age in both spectral channels. In short spectral channel, &#x3c4;m shortening was observed in both AMD models as well, but its rate was more pronounced in ApoE-/- mice and significantly different from the other strains as months of age progressed. In contrast, in long spectral channel, both model strains showed completely opposite trends, with &#x3c4;m becoming shorter in ApoE-/- and longer in Nrf2-/- mice than the others. Oil red O staining at Bruch's membrane was significantly stronger in ApoE-/- mice at 11&#xa0;months than the other strains. Plasma total antioxidant capacity was highest in ApoE-/- mice at both 6 and 11&#xa0;months.<br><br>CONCLUSIONS: The two AMD mouse models exhibited largely different fundus fluorescence lifetime, which might be related to the different systemic metabolic state. FLIO might be able to indicate different metabolic states of eyes at risk for AMD.<br><br>TRANSLATIONAL RELEVANCE: This animal study may provide new insights into the relationship between early AMD-associated metabolic changes and FLIO findings.},
}
@article {pmid38284102,
year = {2024},
author = {Hiya, FE and Liu, JY and Shen, M and Herrera, G and Li, J and Zhang, Q and de Sisternes, L and O'Brien, RC and Rosenfeld, PJ and Gregori, G},
title = {Spectral-Domain and Swept-Source OCT Angiographic Scans Yield Similar Drusen Measurements When Processed with the Same Algorithm.},
journal = {Ophthalmology science},
volume = {4},
number = {3},
pages = {100424},
pmid = {38284102},
issn = {2666-9145},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans.<br><br>DESIGN: Retrospective study.<br><br>PARTICIPANTS: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen.<br><br>METHODS: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm&#xa0;&#xd7;&#xa0;6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson's correlation tests.<br><br>MAIN OUTCOME MEASURES: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles.<br><br>RESULTS: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P&#xa0;<&#xa0;0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all P&#xa0;<&#xa0;0.001).<br><br>CONCLUSIONS: An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38284101,
year = {2024},
author = {Yao, H and Wu, Z and Gao, SS and Guymer, RH and Steffen, V and Chen, H and Hejrati, M and Zhang, M},
title = {Deep Learning Approaches for Detecting of Nascent Geographic Atrophy in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {3},
pages = {100428},
pmid = {38284101},
issn = {2666-9145},
abstract = {PURPOSE: Nascent geographic atrophy (nGA) refers to specific features seen on OCT B-scans, which are strongly associated with the future development of geographic atrophy (GA). This study sought to develop a deep learning model to screen OCT B-scans for nGA that warrant further manual review (an artificial intelligence [AI]-assisted approach), and to determine the extent of reduction in OCT B-scan load requiring manual review while maintaining near-perfect nGA detection performance.<br><br>DESIGN: Development and evaluation of a deep learning model.<br><br>PARTICIPANTS: One thousand eight hundred and eighty four OCT volume scans (49 B-scans per volume) without neovascular age-related macular degeneration from 280 eyes of 140 participants with bilateral large drusen at baseline, seen at 6-monthly intervals up to a 36-month period (from which 40 eyes developed nGA).<br><br>METHODS: OCT volume and B-scans were labeled for the presence of nGA. Their presence at the volume scan level provided the ground truth for training a deep learning model to identify OCT B-scans that potentially showed nGA requiring manual review. Using a threshold that provided a sensitivity of 0.99, the B-scans identified were assigned the ground truth label with the AI-assisted approach. The performance of this approach for detecting nGA across all visits, or at the visit of nGA onset, was evaluated using fivefold cross-validation.<br><br>MAIN OUTCOME MEASURES: Sensitivity for detecting nGA, and proportion of OCT B-scans requiring manual review.<br><br>RESULTS: The AI-assisted approach (utilizing outputs from the deep learning model to guide manual review) had a sensitivity of 0.97 (95% confidence interval [CI]&#xa0;=&#xa0;0.93-1.00) and 0.95 (95% CI&#xa0;=&#xa0;0.87-1.00) for detecting nGA across all visits and at the visit of nGA onset, respectively, when requiring manual review of only 2.7% and 1.9% of selected OCT B-scans, respectively.<br><br>CONCLUSIONS: A deep learning model could be used to enable near-perfect detection of nGA onset while reducing the number of OCT B-scans requiring manual review by over 50-fold. This AI-assisted approach shows promise for substantially reducing the current burden of manual review of OCT B-scans to detect this crucial feature that portends future development of GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38284098,
year = {2024},
author = {Shen, LL and Keenan, JD and Chahal, N and Taha, AT and Saroya, J and Ma, CJ and Sun, M and Yang, D and Psaras, C and Callander, J and Flaxel, C and Fawzi, AA and Schlesinger, TK and Wong, RW and Bryan Leung, LS and Eaton, AM and Steinle, NC and Telander, DG and Afshar, AR and Neuwelt, MD and Lim, JI and Yiu, G and Stewart, JM},
title = {METformin for the MINimization of Geographic Atrophy Progression (METforMIN): A Randomized Trial.},
journal = {Ophthalmology science},
volume = {4},
number = {3},
pages = {100440},
pmid = {38284098},
issn = {2666-9145},
support = {P30 EY001792/EY/NEI NIH HHS/United States ; P30 EY002162/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Metformin use has been associated with a decreased risk of age-related macular degeneration (AMD) progression in observational studies. We aimed to evaluate the efficacy of oral metformin for slowing geographic atrophy (GA) progression.<br><br>DESIGN: Parallel-group, multicenter, randomized phase II clinical trial.<br><br>PARTICIPANTS: Participants aged &#x2265; 55 years without diabetes who had GA from atrophic AMD in &#x2265; 1 eye.<br><br>METHODS: We enrolled participants across 12 clinical centers and randomized participants in a 1:1 ratio to receive oral metformin (2000 mg daily) or observation for 18 months. Fundus autofluorescence imaging was obtained at baseline and every 6 months.<br><br>MAIN OUTCOME MEASURES: The primary efficacy endpoint was the annualized enlargement rate of the square root-transformed GA area. Secondary endpoints included best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) at each visit.<br><br>RESULTS: Of 66 enrolled participants, 34 (57 eyes) were randomized to the observation group and 32 (53 eyes) were randomized to the treatment group. The median follow-up duration was 13.9 and 12.6 months in the observation and metformin groups, respectively. The mean &#xb1; standard error annualized enlargement rate of square root transformed GA area was 0.35 &#xb1; 0.04 mm/year in the observation group and 0.42 &#xb1; 0.04 mm/year in the treatment group (risk difference = 0.07 mm/year, 95% confidence interval = -0.05 to 0.18 mm/year; P = 0.26). The mean &#xb1; standard error decline in BCVA was 4.8 &#xb1; 1.7 letters/year in the observation group and 3.4 &#xb1; 1.1 letters/year in the treatment group (P = 0.56). The mean &#xb1; standard error decline in LLVA was 7.3 &#xb1; 2.5 letters/year in the observation group and 0.8 &#xb1; 2.2 letters/year in the treatment group (P = 0.06). Fourteen participants in the metformin group experienced nonserious adverse events related to metformin, with gastrointestinal side effects as the most common. No serious adverse events were attributed to metformin.<br><br>CONCLUSIONS: The results of this trial as conducted do not support oral metformin having effects on reducing the progression of GA. Additional placebo-controlled trials are needed to explore the role of metformin for AMD, especially for earlier stages of the disease.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38283180,
year = {2024},
author = {Siqueira, RC},
title = {Photobiomodulation Using Light-Emitting Diode (LED) for Treatment of Retinal Diseases.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {18},
number = {},
pages = {215-225},
pmid = {38283180},
issn = {1177-5467},
abstract = {Photobiomodulation (PBM) is a type of phototherapy that employs light-emitting diodes (LEDs) or low-power lasers to selectively administer specific wavelengths of visible light, ranging from 500 to 1000 nm, including near-infrared (NIR) wavelengths. LEDs are advantageous compared to lasers due to their ability to treat large areas at a lower cost, lack of tissue damage potential in humans, and reduced risk of eye-related accidents. The ophthalmology community has recently taken interest in PBM as a promising novel approach for managing various retinal conditions such as age-related macular degeneration, retinopathy of prematurity, retinitis pigmentosa, diabetic retinopathy, Leber's hereditary optic neuropathy, amblyopia, methanol-induced retinal damage, and potentially others. This review critically assesses the existing body of research on PBM applications in the retina, focusing on elucidating the underlying mechanisms of action and evaluating the clinical outcomes associated with this therapeutic modality.},
}
@article {pmid38283058,
year = {2023},
author = {Gómez Sánchez, A and Colucci, P and Moran, A and Moya López, A and Colligris, B and Álvarez, Y and Kennedy, BN},
title = {Systemic treatment with cigarette smoke extract affects zebrafish visual behaviour, intraocular vasculature morphology and outer segment phagocytosis.},
journal = {Open research Europe},
volume = {3},
number = {},
pages = {48},
pmid = {38283058},
issn = {2732-5121},
abstract = {INTRODUCTION: Cigarette smoking adversely affects multiple aspects of human health including eye disorders such as age-related macular degeneration, cataracts and dry eye disease. However, there remains a knowledge gap in how constituents of cigarette smoke affect vision and retinal biology. We used zebrafish to assess effects of short-term acute exposure to cigarette smoke extract (CSE) on visual behaviour and retinal biology.<br><br>METHODS: Zebrafish larvae with a developed visual system at three days post-fertilization (dpf) were exposed to CSE for 4, 24 or 48 hours. Visual behaviour, hyaloid vasculature morphology, retinal histology, oxidative stress gene expression and outer segment phagocytosis were investigated using visual behavioural optokinetic and visual motor response assays (OKR and VMR), microscopy (light, fluorescence and transmission electron microscopy), and real-time PCR.<br><br>RESULTS: In zebrafish larvae, 48 hours of CSE treatment resulted in significantly reduced visual behaviour. Larvae treated with 10, 15 or 20 &#x3bc;g/mL CSE showed an average of 13.7, 10.7 or 9.4 saccades per minute, respectively, significantly lower compared with 0.05% DMSO controls (p=0.0093, p=0.0004 and p<0.0001, respectively) that exhibited 19.7 saccades per minute. The diameter of intraocular vessels increased from 4.833 &#x3bc;m in 0.05% DMSO controls to 5.885 &#x3bc;m in the 20 &#x3bc;g/mL CSE-treated larvae (p=0.0333). Biometry analysis highlighted a significant axial length elongation in 20 &#x3bc;g/mL CSE-treated larvae (216.9 &#x3bc;m, p<0.0001) compared to 0.05% dimethyl sulfoxide (DMSO) controls (205.1 &#x3bc;m). Larvae exposed to 20 &#x3bc;g/mL CSE had significantly (p=0.0002) higher numbers of RPE phagosomes compared to vehicle controls (0.1425 and 0.093 phagosomes/&#x3bc;m RPE, respectively).<br><br>CONCLUSIONS: Zebrafish larvae with a developed visual system display apparent defects in visual behaviour and retinal biology after acute exposure to CSE, establishing a valuable in vivo model to investigate ocular disorders related to cigarette smoke.},
}
@article {pmid38280029,
year = {2024},
author = {Grzybowski, A and Sulaviková, Z and Gawęcki, M and Kozak, I},
title = {Subthreshold laser treatment in retinal diseases: a mini review.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {7},
pages = {2337-2344},
pmid = {38280029},
issn = {1435-702X},
mesh = {Humans ; *Retinal Diseases/surgery ; *Laser Coagulation/methods ; Tomography, Optical Coherence/methods ; Visual Acuity ; Retinal Pigment Epithelium/pathology ; },
abstract = {PURPOSE: To summarize the mechanism and the clinical applications of subthreshold laser (STL) in retinal practice. Subthreshold or "non-destructive" laser includes all types of laser treatments that produce minimal or no damage to the tissues and no visible signs after application.<br><br>METHODS: A descriptive review of articles from literature databases (PubMed, Medline, Embase, Cochrane, Web of Science) published before August 2023, which discuss current STL treatments of retinal diseases.<br><br>RESULTS: This review provides evidence for STL as a treatment option for central serous chorioretinopathy, diabetic retinopathy, age-related macular degeneration, macular edema due to retinal vein occlusion, and other maculopathies. In most published reports, STL has shown a therapeutic effect without damage to the underlying tissue.<br><br>CONCLUSION: Subthreshold laser treatment has shown safety and efficacy in the management of some retinal and macular diseases. Stimulation of the retinal pigment epithelium without destroying adjacent neuroretina has been shown to be sufficient in inducing retinal repair in many clinical cases. Recent research and clinical studies continue to explore the mechanisms and improving therapeutic benefits of this technology as well as extend the range of retinal disorders treatable by this modality.},
}
@article {pmid38279349,
year = {2024},
author = {Chao, WW and Chao, HW and Lee, HF and Chao, HM},
title = {The Effect of S-Allyl L-Cysteine on Retinal Ischemia: The Contributions of MCP-1 and PKM2 in the Underlying Medicinal Properties.},
journal = {International journal of molecular sciences},
volume = {25},
number = {2},
pages = {},
pmid = {38279349},
issn = {1422-0067},
mesh = {Rats ; Animals ; Rats, Wistar ; Cysteine/pharmacology/therapeutic use ; Hydrogen Peroxide/therapeutic use ; *Reperfusion Injury/drug therapy ; *Retinal Diseases/drug therapy ; Ischemia/drug therapy ; *Neuroprotective Agents/pharmacology/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; *Glaucoma/drug therapy ; },
abstract = {Retinal ischemia plays a vital role in vision-threatening retinal ischemic disorders, such as diabetic retinopathy, age-related macular degeneration, glaucoma, etc. The aim of this study was to investigate the effects of S-allyl L-cysteine (SAC) and its associated therapeutic mechanism. Oxidative stress was induced by administration of 500 μM H2O2 for 24 h; SAC demonstrated a dose-dependent neuroprotective effect with significant cell viability effects at 100 μM, and it concurrently downregulated angiogenesis factor PKM2 and inflammatory biomarker MCP-1. In a Wistar rat model of high intraocular pressure (HIOP)-induced retinal ischemia and reperfusion (I/R), post-administration of 100 μM SAC counteracted the ischemic-associated reduction of ERG b-wave amplitude and fluorogold-labeled RGC reduction. This study supports that SAC could protect against retinal ischemia through its anti-oxidative, anti-angiogenic, anti-inflammatory, and neuroprotective properties.},
}
@article {pmid38279294,
year = {2024},
author = {Kocherlakota, S and Baes, M},
title = {Benefits and Caveats in the Use of Retinal Pigment Epithelium-Specific Cre Mice.},
journal = {International journal of molecular sciences},
volume = {25},
number = {2},
pages = {},
pmid = {38279294},
issn = {1422-0067},
support = {C14/18/088//KU Leuven/ ; FWO G0A8619N//Research Foundation - Flanders/ ; },
mesh = {Mice ; Animals ; *Retinal Pigment Epithelium/metabolism ; Retina ; Photoreceptor Cells ; *Macular Degeneration/genetics/metabolism ; Proteins/metabolism ; Mice, Knockout ; },
abstract = {The retinal pigment epithelium (RPE) is an important monolayer of cells present in the outer retina, forming a major part of the blood-retina barrier (BRB). It performs many tasks essential for the maintenance of retinal integrity and function. With increasing knowledge of the retina, it is becoming clear that both common retinal disorders, like age-related macular degeneration, and rare genetic disorders originate in the RPE. This calls for a better understanding of the functions of various proteins within the RPE. In this regard, mice enabling an RPE-specific gene deletion are a powerful tool to study the role of a particular protein within the RPE cells in their native environment, simultaneously negating any potential influences of systemic changes. Moreover, since RPE cells interact closely with adjacent photoreceptors, these mice also provide an excellent avenue to study the importance of a particular gene function within the RPE to the retina as a whole. In this review, we outline and compare the features of various Cre mice created for this purpose, which allow for inducible or non-inducible RPE-specific knockout of a gene of interest. We summarize the various benefits and caveats involved in the use of such mouse lines, allowing researchers to make a well-informed decision on the choice of Cre mouse to use in relation to their research needs.},
}
@article {pmid38279157,
year = {2024},
author = {Zhou, W and Huang, Z and Xu, K and Li, Y and Li, X and Li, J and Jin, Y and Snellingen, T and Liang, L},
title = {Transpalpebral electrical stimulation for the treatment of retinitis pigmentosa: study protocol for a series of N-of-1 single-blind, randomized controlled trial.},
journal = {Trials},
volume = {25},
number = {1},
pages = {89},
pmid = {38279157},
issn = {1745-6215},
support = {82274589//National Natural Science Foundation of China/ ; 81973912//National Natural Science Foundation of China/ ; CI2021A02602//Science and Technology Innovation Project in China Academy of Chinese Medical Sciences/ ; 2020YJSZX-2//China Center for Evidence-based Medicine of Traditional Chinese Medicine Special Project for Director of Business Research Office/ ; },
mesh = {Humans ; Prospective Studies ; Single-Blind Method ; Visual Acuity ; *Retinitis Pigmentosa/diagnosis/therapy ; Blindness ; Electric Stimulation/methods ; Randomized Controlled Trials as Topic ; },
abstract = {BACKGROUND: Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive loss of rod photoreceptors of the eye, leading to irreversible blindness. To date, to our knowledge, no clinical prospective studies have been undertaken that could document the effect of interventions that could reverse or reduce the progression of this disease. The application of microcurrent stimulation (ES) of the eye in the treatment of chronic eye diseases such as glaucoma and age-related macular degeneration has been used over several decades and has been reported to have beneficial effects to reduce the progression of these blinding diseases and has been supported by animal studies and smaller clinical studies, but to date, no large randomized clinical trials on the use of microcurrent therapy have been published. More recent clinical reports have also shown beneficial effects of ES on slowing the progression of RP but also lacks data from robust prospective clinical outcome studies. To our knowledge, this is the first prospective randomized study to evaluate the safety and clinical effectiveness of transpalpebral electrical stimulation (TpES) on the progression of RP.<br><br>METHODS: Randomized prospective study using N-of-1 trial 3 single-blind, crossover comparisons. The intervention period of each comparison is divided into treatment period and control period which are randomized arranged. Twelve participants will be strictly recruited in N-of-1 trial by the researcher in accordance with the inclusion and exclusion criteria. The main outcome of interest examined after each cycle of the 8-week intervention period is the assessment of the visual field (VF). Other variables of interest are best corrected visual acuity (BCVA), retinal function using electroretinogram (ERG), and visual function using NEI VFQ-25 questionnaire. Objective assessments of retinal changes will be undertaken using optical coherence tomography (OCT) and fundus autofluorescence (FAF).<br><br>DISCUSSION: The trial will evaluate the efficacy and safety of microcurrent stimulation on RP and provide high-quality evidence for clinical application through N-of-1 trial.<br><br>TRIAL REGISTRATION: Chinese Clinical Trial Registry; ChiCTR2300067357; https://www.chictr.org.cn/showproj.html?proj=174635 .&#xa0;Registered on&#xa0;5 January 2023.},
}
@article {pmid38279038,
year = {2024},
author = {Gigon, A and Iskandar, A and Kasser, S and Naso, S and Zola, M and Mantel, I},
title = {Short-term response to anti-VEGF as indicator of visual prognosis in refractory age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {7},
pages = {1342-1348},
pmid = {38279038},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Male ; Retrospective Studies ; Female ; *Intravitreal Injections ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Prognosis ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Aged, 80 and over ; *Ranibizumab/therapeutic use/administration &amp; dosage ; *Subretinal Fluid ; Bevacizumab/therapeutic use ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; },
abstract = {BACKGROUND: Some patients with neovascular age-related macular degeneration (nAMD) respond insufficiently to anti-VEGF treatment despite maximal monthly intravitreal injections. Their short-term response between injections was investigated for extent and visual prognosis.<br><br>SUBJECTS/METHODS: Monocentric retrospective observational study. 45 eyes from 41 patients with refractory nAMD (who previously received at least 12 months of anti-VEGF treatment), evaluated by optical coherence tomography (OCT) in between monthly anti-VEGF injections. The fluid profile on OCT was evaluated before, 1 week after, and 1 month after an intravitreal injection, using central retinal thickness (CRT), manual measurements, and fluid specific volumetric measurements performed by an automated algorithm based on artificial intelligence.<br><br>RESULTS: A significant improvement was found at week 1 in terms of CRT (p&#x2009;<&#x2009;0.0001), intraretinal (IRF) (p&#x2009;=&#x2009;0.007), subretinal fluid (SRF) (p&#x2009;<&#x2009;0.0001), and pigment epithelium detachment (PED) volume (p&#x2009;<&#x2009;0.0001). Volumetric fluid measures revealed a&#x2009;>50% reduction at week 1 for both IRF and SRF for approximately two-thirds of eyes. Poorer short-term response was associated with larger exudative fluid amounts (IRF&#x2009;+&#x2009;SRF) (p&#x2009;=&#x2009;0.003), larger PED (p&#x2009;=&#x2009;0.007), lower visual acuity (p&#x2009;=&#x2009;0.004) and less anatomic changes at treatment initiation (p&#x2009;<&#x2009;0.0001). Univariate and multivariate analysis revealed that visual outcomes 4 and 5 years later was significantly worse with weaker short-term responsiveness (p&#x2009;=&#x2009;0.005), with the presence of atrophy (p&#x2009;=&#x2009;0.01) and larger PED volumes (p&#x2009;=&#x2009;0.002).<br><br>CONCLUSIONS: Incomplete responders to anti-VEGF showed a significant short-term response, identifiable at 1 week after injection, with rapid recurrence at 1 month. Weaker short-term responsiveness at 1 week was associated with poorer long term visual prognosis. These patients may need adjuvant treatment to improve their prognosis.},
}
@article {pmid38278777,
year = {2024},
author = {Sénéclauze, A and Le Goff, M and Cougnard-Grégoire, A and Korobelnik, JF and Rougier, MB and Delyfer, MN and Delcourt, C and Gattoussi, S},
title = {Associations of drusen location with risk factors and incidence of late age-related macular degeneration in the Alienor study.},
journal = {Acta ophthalmologica},
volume = {102},
number = {5},
pages = {e813-e822},
doi = {10.1111/aos.16645},
pmid = {38278777},
issn = {1755-3768},
support = {//Caisse nationale de solidarit&#xe9; pour l'autonomie/ ; //Agence Nationale de la Recherche/ ; //Universit&#xe9; de Bordeaux/ ; //Laboratoires Th&#xe9;a/ ; //Fondation Voir et&#xa0;Entendre/ ; },
mesh = {Humans ; *Retinal Drusen/diagnosis/epidemiology ; Female ; Male ; Incidence ; Risk Factors ; Prospective Studies ; Aged ; France/epidemiology ; Follow-Up Studies ; Middle Aged ; Macular Degeneration/epidemiology/diagnosis/etiology ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; },
abstract = {PURPOSE: To test the hypothesis that central drusen location is strongly linked with known Age-related Macular Degeneration (AMD) risk factors and risk of incident late AMD.<br><br>METHODS: The Alienor study is a prospective population-based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63&#x2009;&#x3bc;m) within 500&#x2009;&#x3bc;m from fovea and pericentral drusen as at least one drusen 500-3000&#x2009;&#x3bc;m from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS).<br><br>RESULTS: In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack-years, p&#x2009;=&#x2009;0.02), HDL-cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p&#x2009;=&#x2009;0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p&#x2009;=&#x2009;0.04), Age-Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11-1.83) and complement GRS (OR, 1.55; 95% CI, 1.15-2.10). In Cox modelling, the central location of drusen (at baseline or during the follow-up) was associated with a 4.41-fold increased risk (95% CI,1.98-9.81) for an incident late AMD.<br><br>CONCLUSION: Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression.},
}
@article {pmid38278174,
year = {2024},
author = {Duic, C and Mukherjee, S and Pfau, K and Thavikulwat, A and Domalpally, A and Keenan, TDL and Chew, E and Cukras, C},
title = {Local and Global Associations of Reticular Pseudodrusen in Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {7},
pages = {646-656},
doi = {10.1016/j.oret.2024.01.016},
pmid = {38278174},
issn = {2468-6530},
mesh = {Humans ; *Retinal Drusen/diagnosis/etiology ; Female ; *Tomography, Optical Coherence/methods ; Male ; Aged ; Follow-Up Studies ; *Fluorescein Angiography/methods ; *Fundus Oculi ; Aged, 80 and over ; Visual Acuity ; Macular Degeneration/diagnosis ; Multimodal Imaging ; Retina/pathology/diagnostic imaging ; Middle Aged ; Dark Adaptation/physiology ; Disease Progression ; },
abstract = {PURPOSE: To investigate the spatial distribution of reticular pseudodrusen (RPD) in eyes with age-related macular degeneration (AMD) and their correlation with functional measures, retinal thickness, and changes over time.<br><br>DESIGN: Longitudinal, cohort study.<br><br>PARTICIPANTS: Thirty-five participants with RPD and spectrum of AMD severity (including no AMD).<br><br>METHODS: Multimodal imaging was graded by a reading center, including evaluation of color fundus imaging to assess AMD severity scores. Reticular pseudodrusen presence on OCT volumes was confirmed on en face imaging and the RPD extent was contoured on infrared images. One study eye per participant underwent rod-mediated dark adaptation, measuring rod intercept time (RIT) at 5&#xb0; and, if needed, 12&#xb0; superior to the fovea.<br><br>MAIN OUTCOME MEASURES: The primary outcome was RIT and OCT thickness measures which were correlated with RPD area.<br><br>RESULTS: A total of 51 eyes had &#x2265; 1 visit with RPD detected (mean follow-up, 2.19 &#xb1; 2.04 years; range, 0-5 years), totaling 169 eye-based visits with RPD. Of the 51 eyes with RPD, 5 (9.8%) developed geographic atrophy and 17 (33.3%) progressed to neovascular AMD. Larger RPD areas were detected more frequently in AMD severity scores 6-7. Reticular pseudodrusen area within an eye generally increased over time. The lesion distribution showed a predilection for the superior retina, especially the outer superior subfield of the ETDRS grid, with the central subfield having least involvement. Reticular pseudodrusen area was inversely correlated with central subfield thickness and positively correlated with RIT at 5&#xb0; (P&#xa0;= 0.001; r[2]&#xa0;= 0.01) and 12&#xb0; (P&#xa0;= 0.004; r[2]&#xa0;=&#xa0;0.01). Rod-mediated dark adaptation at 5&#xb0; reached the test ceiling in > 85% of visits, irrespective of RPD lesion presence/absence at the test location. Retinal thickness decreased monotonically, with the central subfield demonstrating the greatest percentage change over 5 years (&#x394;&#xa0;=&#xa0;-5.47%).<br><br>CONCLUSIONS: In AMD, RPD involve predominantly the superior retina but can involve all ETDRS subfields and evolve over time. Eyes with RPD exhibit structural and functional impairments that can be measured beyond the boundaries of the RPD lesions, suggesting changes associated with RPD are associated with both local changes and a more widespread process.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38276971,
year = {2024},
author = {Yalla, GR and Kuriyan, AE},
title = {Cell therapy for retinal disease.},
journal = {Current opinion in ophthalmology},
volume = {35},
number = {3},
pages = {178-184},
doi = {10.1097/ICU.0000000000001034},
pmid = {38276971},
issn = {1531-7021},
mesh = {Humans ; *Retinal Diseases/therapy ; *Macular Degeneration/therapy ; *Retinitis Pigmentosa ; Stem Cell Transplantation ; Cell- and Tissue-Based Therapy ; },
abstract = {PURPOSE OF REVIEW: This review presents an update on completed stem cell therapy trials aimed at retinal diseases.<br><br>RECENT FINDINGS: In recent years, several clinical trials have been conducted examining the safety and role of cell therapy in diseases, including age-related macular degeneration, Stargardt's macular dystrophy, and retinitis pigmentosa. Studies have utilized a variety of cell lines, modes of delivery, and immunosuppressive regimens. The prevalence of fraudulent cell therapy clinics poses threats to patients.<br><br>SUMMARY: Clinical trials have begun to characterize the safety of cell therapy in retinal disease. While studies have described the potential benefits of cell therapy, larger studies powered to evaluate this efficacy are required to continue progressing toward preventing retinal disease. Nonapproved cell therapy clinics require regulation and patient education to avoid patient complications.},
}
@article {pmid38276142,
year = {2024},
author = {Žugelj, N and Peterlin, L and Muznik, U and Klobučar, P and Jaki Mekjavić, P and Vidović Valentinčić, N and Fakin, A},
title = {Face Recognition Characteristics in Patients with Age-Related Macular Degeneration Determined Using a Virtual Reality Headset with Eye Tracking.},
journal = {Journal of clinical medicine},
volume = {13},
number = {2},
pages = {},
pmid = {38276142},
issn = {2077-0383},
support = {J3-1750//Slovenian Research Agency/ ; 20220038//University Medical Centre Ljubljana, Slovenia/ ; },
abstract = {BACKGROUND AND OBJECTIVES: Face recognition is one of the most serious disabilities of patients with age-related macular degeneration (AMD). Our purpose was to study face recognition using a novel method incorporating virtual reality (VR) and eye tracking.<br><br>MATERIALS AND METHODS: Eighteen patients with AMD (seven male; median age 83 years; 89% with bilateral advanced AMD) and nineteen healthy controls (five male; median age 68 years) underwent the face recognition test IC FACES (Synthesius, Ljubljna, Slovenia) on a VR headset with built-in eye tracking sensors. Analysis included recognition accuracy, recognition time and fixation patterns. Additionally, a screening test for dementia and imaging with fundus autofluorescence and optical coherence tomography was performed.<br><br>RESULTS: AMD patients had significantly lower face recognition accuracy (42% vs. 92%; p < 0.001) and longer recognition time (median 4.0 vs. 2.0 s; p < 0.001) in comparison to controls. Both parameters were significantly worse in patients with lower visual acuity. In both groups, eye-tracking data revealed the two classical characteristics of the face recognition process, i.e., fixations clustering mainly in the nose-eyes-mouth triangle and starting observation in the nasal area.<br><br>CONCLUSIONS: The study demonstrates usability of a VR headset with eye tracking for studying visual perception in real-world situations which could be applicable in the design of clinical studies.},
}
@article {pmid38275412,
year = {2024},
author = {Jo, G and Chae, JB and Jung, SA and Lyu, J and Chung, H and Lee, JH},
title = {Sulfated CXCR3 Peptide Trap Use as a Promising Therapeutic Approach for Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {12},
number = {1},
pages = {},
pmid = {38275412},
issn = {2227-9059},
support = {2022R1F1A1060081//Ministry of Education/ ; 2019M3A9H1030948//Ministry of Science and ICT/ ; },
abstract = {BACKGROUND AND OBJECTIVES: Chemokines have various biological functions and potential roles in the development or progression of neuroinflammatory diseases. However, the specific pathogenic roles of chemokines in the major cause for vision loss among the elderly, the leading cause of blindness in older individuals, remain elusive. Chemokines interact with their receptors expressed in the endothelium and on leukocytes. The sulfation of tyrosine residues in chemokine receptors increases the strength of ligand-receptor interaction and modulates signaling. Therefore, in the present study, we aimed to construct a human recombinant sulfated CXCR3 peptide trap (hCXCR3-S2) and mouse recombinant sulfated CXCR3 peptide trap (mCXCR3-S2) to demonstrate in vivo effects in preventing choroidal neovascularization (CNV) and chemotaxis.<br><br>MATERIALS AND METHODS: We generated expression vectors for mCXCR3-S2 and hCXCR3-S2 with GST domains and their respective cDNA sequences. Following overexpression in E. coli BL21 (DE3), we purified the fusion proteins from cell lysates using affinity chromatography. First, the impact of hCXCR3-S2 was validated in vitro. Subsequently, the in vivo efficacy of mCXCR3-S2 was investigated using a laser-induced CNV mouse model, a mouse model of neovascular age-related macular degeneration (AMD).<br><br>RESULTS: hCXCR3-S2 inhibited the migration and invasion of two human cancer cell lines. Intravitreal injection of mCXCR3-S2 attenuated CNV and macrophage recruitment in neovascular lesions of mouse models. These in vitro and in vivo effects were significantly stronger with CXCR3-S2 than with wild-type CXCR3 peptides.<br><br>CONCLUSION: These findings demonstrate that the sulfated form of the CXCR3 peptide trap is a valuable tool that could be supplemented with antivascular endothelial growth factors in AMD treatment.},
}
@article {pmid38275379,
year = {2023},
author = {Blekeris, T and Gedvilaite, G and Kaikaryte, K and Kriauciuniene, L and Zaliuniene, D and Liutkevciene, R},
title = {Association of STAT4 Gene Polymorphisms (rs10181656, rs7574865, rs7601754, rs10168266) and Serum STAT4 Levels in Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {12},
number = {1},
pages = {},
pmid = {38275379},
issn = {2227-9059},
abstract = {UNLABELLED: Age-related macular degeneration (AMD) is a progressive degenerative disease that affects the central part of the retina: the macula. AMD is the most common cause of central vision loss in industrialized countries. Increasing attention is being paid to the study of genetic factors that may influence the manifestation of AMD. STAT4 protein is involved in the pathogenesis of numerous inflammatory processes, so we decided to investigate the association between STAT4 gene polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) and age-related macular degeneration.<br><br>PURPOSE: To investigate the association between STAT4 (rs10181656, rs7574865, rs7601754, and rs10168266) gene polymorphisms and STAT4 serum levels in patients with age-related macular degeneration.<br><br>METHODS AND PARTICIPANTS: The study included 150 individuals with early AMD, 150 individuals with exudative AMD, and 200 healthy subjects. DNA was extracted from peripheral blood leukocytes using the DNA salting-out method, and the genotyping was performed using a real-time polymerase chain reaction (RT-PCR) method. STAT4 serum levels were evaluated using the ELISA method. Statistical analysis was performed using "IBM SPSS "Statistics 29.0" software".<br><br>RESULTS: The study revealed no statistically significant differences in the distribution of genotypes and alleles for the STAT4 polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) between patients with AMD and the control group. Similarly, a gender-based analysis did not yield any significant differences in the genotype or allele frequencies. Age group comparisons also showed no statistically significant variations in the presence of these STAT4 polymorphisms between AMD patients and the control group. However, notably, individuals with exudative AMD displayed lower levels of serum STAT4 in comparison to the control group (median (IQR): 0.118 (0.042) vs. 0.262 (0.385), p = 0.005).<br><br>CONCLUSION: Investigating STAT4 gene polymorphisms (rs10181656, rs7574865, rs7601754, and rs10168266) did not reveal a significant association with AMD. However, further analysis demonstrated intriguing findings regarding serum STAT4 levels. Exudative AMD patients with at least one G allele of the STAT4 rs10181656 exhibited significantly lower serum STAT4 levels than the control group subjects (p = 0.011). Similarly, those with at least one T allele of STAT4 rs10168266 had lower serum STAT4 levels compared to the control group subjects (p = 0.039). These results suggest a potential link between specific STAT4 genotypes and serum STAT4 levels in exudative AMD patients, shedding light on a novel aspect of the disease.},
}
@article {pmid38273689,
year = {2024},
author = {Dabir, S and Mohankumar, A and Rao, VP and Rajan, M},
title = {Retinal pigment epithelium rip with posterior uveitis after intravitreal brolucizumab in neovascular age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {2},
pages = {292-294},
pmid = {38273689},
issn = {1998-3689},
mesh = {Humans ; Retinal Pigment Epithelium ; Antibodies, Monoclonal, Humanized/adverse effects ; *Uveitis, Posterior/diagnosis/drug therapy ; *Macular Degeneration ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
}
@article {pmid38273100,
year = {2024},
author = {Clinton, S and Hoad, G and Bloomfield, P and Malcolm, E and Searle, K and Jarman, S and Barber, R and Tucker, S},
title = {Comparing views of patients and eye care professionals on the information provided on age-related macular degeneration and diabetic macular oedema.},
journal = {Eye (London, England)},
volume = {38},
number = {8},
pages = {1591-1593},
pmid = {38273100},
issn = {1476-5454},
mesh = {Humans ; *Macular Edema ; *Diabetic Retinopathy ; *Macular Degeneration ; Male ; Female ; Patient Education as Topic ; Aged ; Middle Aged ; Surveys and Questionnaires ; },
}
@article {pmid38271674,
year = {2024},
author = {Maywood, MJ and Parikh, R and Deobhakta, A and Begaj, T},
title = {PERFORMANCE ASSESSMENT OF AN ARTIFICIAL INTELLIGENCE CHATBOT IN CLINICAL VITREORETINAL SCENARIOS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {6},
pages = {954-964},
doi = {10.1097/IAE.0000000000004053},
pmid = {38271674},
issn = {1539-2864},
mesh = {Humans ; Cross-Sectional Studies ; Retrospective Studies ; *Artificial Intelligence ; *Retinal Diseases/surgery ; *Vitreoretinal Surgery ; },
abstract = {PURPOSE: To determine how often ChatGPT is able to provide accurate and comprehensive information regarding clinical vitreoretinal scenarios. To assess the types of sources ChatGPT primarily uses and to determine whether they are hallucinated.<br><br>METHODS: This was a retrospective cross-sectional study. The authors designed 40 open-ended clinical scenarios across four main topics in vitreoretinal disease. Responses were graded on correctness and comprehensiveness by three blinded retina specialists. The primary outcome was the number of clinical scenarios that ChatGPT answered correctly and comprehensively. Secondary outcomes included theoretical harm to patients, the distribution of the type of references used by the chatbot, and the frequency of hallucinated references.<br><br>RESULTS: In June 2023, ChatGPT answered 83% of clinical scenarios (33/40) correctly but provided a comprehensive answer in only 52.5% of cases (21/40). Subgroup analysis demonstrated an average correct score of 86.7% in neovascular age-related macular degeneration, 100% in diabetic retinopathy, 76.7% in retinal vascular disease, and 70% in the surgical domain. There were six incorrect responses with one case (16.7%) of no harm, three cases (50%) of possible harm, and two cases (33.3%) of definitive harm.<br><br>CONCLUSION: ChatGPT correctly answered more than 80% of complex open-ended vitreoretinal clinical scenarios, with a reduced capability to provide a comprehensive response.},
}
@article {pmid38271426,
year = {2024},
author = {Dogan, L and Tanriverdi, D and Gungor, K},
title = {Assessment of vision-related quality of life and depression in patients with age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 2},
pages = {S293-S297},
pmid = {38271426},
issn = {1998-3689},
mesh = {Male ; Humans ; Female ; Aged ; *Quality of Life ; Cross-Sectional Studies ; Depression/diagnosis/epidemiology/etiology ; *Macular Degeneration/complications/diagnosis/epidemiology ; Visual Acuity ; Surveys and Questionnaires ; },
abstract = {PURPOSE: To evaluate the effect of age-related macular degeneration (AMD) on vision-related quality of life (VRQOL) and depression levels.<br><br>METHODS: This cross-sectional study included 143 patients who are being followed up with a diagnosis of AMD. The Turkish versions of the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and Geriatric Depression Scale-15 (GDS-15) were directed to the patients. The questionnaire results were analyzed based on the severity, treatment procedures for AMD, and sociodemographic characteristics of patients.<br><br>RESULTS: The subscale scores obtained from the NEI VFQ-25 ranged from 47.54 for "near activities" to 84.02 for "color vision." Of the patients, 59.4% (85/143) were compatible with depression according to the GDS-15 questionnaire. There was no significant difference in the NEI VFQ-25 subscale scores between the gender groups (P > 0.05), whereas females were statistically significantly more depressive than males (P < 0.05). There were no significant differences between the injection (anti-vascular endothelial growth factors [anti-VEGF]) group and the non-injection group in terms of subscales of the NEI VFQ-25 questionnaire (P > 0.05). The depression ratio in the non-injected group was statistically significantly higher (P < 0.05).<br><br>CONCLUSION: According to the present study, the association between depression and AMD is a fact that should be highlighted. Patients with depression had lower scores on the quality of life (QOL) test. Previous intravitreal injection did not affect NEI VFQ-25 scores. Female patients with AMD had higher rates of depression and lower visual acuity levels.},
}
@article {pmid38271421,
year = {2024},
author = {Hostovsky, A and Moroz, I and Katz, G},
title = {Aflibercept monotherapy or bevacizumab first for diabetic macular edema.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 2},
pages = {S260-S264},
pmid = {38271421},
issn = {1998-3689},
mesh = {Humans ; Bevacizumab ; *Macular Edema/diagnosis/drug therapy/etiology ; *Diabetic Retinopathy/complications/diagnosis/drug therapy ; Angiogenesis Inhibitors ; Receptors, Vascular Endothelial Growth Factor ; Ranibizumab ; Recombinant Fusion Proteins/therapeutic use ; Intravitreal Injections ; Retrospective Studies ; *Diabetes Mellitus ; },
abstract = {PURPOSE: Clinical outcome and switch patterns with bevacizumab first treatment strategy for patients with newly diagnosed neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Retrospective observational study of the number of intravitreal injections of bevacizumab and treatment switch in patients who started intravitreal bevacizumab injections between January 1, 2016 and December 30, 2018.<br><br>RESULTS: From January 1 2016 to December 31 2018, 608 eyes of 565 patients started intravitreal injections of bevacizumab for a new diagnosis of nAMD. Average visual acuity (VA) at presentation was 0.60 logarithm of the minimum angle of resolution (logMAR), which improved to 0.47 after six injections (P < 0.001) and decreased to 0.63 at the last follow-up (P = 0.543). Switch of treatment was recommended for 190 eyes (31.3%), and of them, 91 patients (15%) were switched during the first 6 months and defined as primary failure of bevacizumab. The switch of treatment resulted in a statistically significant improvement in VA in the first 6 months after the switch. The gain in VA was not sustainable over time.<br><br>CONCLUSION: Bevacizumab first treatment strategy produced results that were comparable to previous real-world outcomes publications of ranibizumab and aflibercept treatment with low rates of failure of bevacizumab treatment. Treatment switch to second-line treatment yielded a significant VA improvement, mainly in patients with primary bevacizumab failure.},
}
@article {pmid38270081,
year = {2024},
author = {Jaffe, GJ and Khanani, AM},
title = {Two studies to learn if avacincaptad pegol works and is safe in people with geographic atrophy: a plain language summary of the GATHER1 and GATHER 2 studies.},
journal = {Immunotherapy},
volume = {16},
number = {4},
pages = {205-221},
doi = {10.2217/imt-2023-0274},
pmid = {38270081},
issn = {1750-7448},
mesh = {Humans ; *Geographic Atrophy/drug therapy ; *Macular Degeneration/drug therapy ; },
abstract = {WHAT IS THIS SUMMARY ABOUT?: This is a summary of two publications. One publication is about the GATHER1 study, which was published in the journal Ophthalmology in 2021. The other publication is about the GATHER2 study, which was published in the journal The Lancet in 2023. Both studies included adult participants with geographic atrophy (GA). GA is an advanced form of dry age-related macular degeneration (dry AMD). The participants in both studies each received treatment in one of their eyes. In both studies, the researchers wanted to learn if avacincaptad pegol (ACP) could help to slow the worsening of the participants' GA over time.<br><br>WHAT WERE THE RESULTS?: In these studies, the researchers found that ACP helped to slow the growth of the GA area in the participants' eyes compared with a sham injection. Participants who received ACP had a similar ability to read differently sized letters on a chart 1&#xa0;year after treatment compared with participants who received no ACP through a sham injection. In the GATHER1 study, none of the participants had serious medical problems in the eye that received the injection. In the GATHER2 study, 2 out of 225 participants (less than 1%) who received ACP had serious medical problems in the eye that received the injection. In the group who received the sham injection, 2 out of the 222 participants (less than 1%) had serious medical problems in the eye that received the sham injection.<br><br>WHAT DO THE RESULTS MEAN?: ACP could be a treatment option for people with GA. The results from several studies are needed to decide which treatments work best and are safest. Other studies may provide new information or different results. Always talk to a doctor before making any treatment changes.},
}
@article {pmid38266962,
year = {2024},
author = {Rothman, AL and Beca, FA and Tijerina, JD and Schuman, DM and Parrish, RK and Vanner, EA and Liu, KC},
title = {Glaucoma Tube Outcomes with and without Anti-VEGF in Patients with Age-related Macular Degeneration.},
journal = {Ophthalmology. Glaucoma},
volume = {7},
number = {3},
pages = {260-270},
doi = {10.1016/j.ogla.2024.01.002},
pmid = {38266962},
issn = {2589-4196},
mesh = {Humans ; Retrospective Studies ; *Intraocular Pressure/physiology ; Female ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Glaucoma Drainage Implants ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Follow-Up Studies ; Visual Acuity ; Aged, 80 and over ; Treatment Outcome ; Bevacizumab/administration &amp; dosage/therapeutic use ; Ranibizumab/administration &amp; dosage ; },
abstract = {PURPOSE: To compare glaucoma tube outcomes of wet age-related macular degeneration (AMD) eyes receiving anti-VEGF injections versus dry AMD eyes and no anti-VEGF.<br><br>DESIGN: Retrospective clinical cohort study.<br><br>PARTICIPANTS: Patients with wet AMD and a history of anti-VEGF within a year prior or after stand-alone glaucoma tube surgery and eyes with dry AMD and no history of anti-VEGF with at least 6 months of follow-up. Eyes with neovascular glaucoma or anti-VEGF for reason other than wet AMD were excluded.<br><br>METHODS: A Kaplan-Meier analysis compared survival for wet versus dry AMD eyes. Failure was defined as intraocular pressure (IOP) > 21 mmHg or < 20% IOP reduction from baseline or IOP &#x2264; 5 mmHg for 2 consecutive postoperative visits starting at month 3, additional glaucoma surgery, or no light perception. Complete success was defined as no failure or medications at final follow-up. Hypertensive phase was defined for valved tubes as IOP > 21 mmHg within 3 months of surgery after a reduction to < 22 mmHg during the first postoperative week. Intraocular pressure, percent reduction in IOP, number of glaucoma medications, and early (< 1 year) and late (>&#xa0;1 year) complications were compared through 5 years.<br><br>MAIN OUTCOME MEASURES: Survival analysis, IOP, number of medications.<br><br>RESULTS: Baseline IOP, number of medications, or tube type were not significantly different between wet (n&#xa0;= 24) and dry AMD eyes (n&#xa0;= 54). No wet AMD eyes failed versus 10 (18%) dry AMD eyes (P&#xa0;= 0.03). Five-year survival was estimated as 100% for wet AMD and 72% for dry AMD (P&#xa0;= 0.04). Wet AMD eyes had lower IOP (10.6 vs. 12.7 mmHg, P&#xa0;= 0.05), greater IOP reduction (60% vs. 49%, P&#xa0;= 0.04), fewer medications (1.2 vs. 2.1, P&#xa0;= 0.02), and more complete success (50% vs. 15%, P&#xa0;= 0.001) at final follow-up (32 vs. 36 months, P&#xa0;= 0.42). Fewer wet than dry AMD eyes experienced hypertensive phase (0/10 [0%] vs. 4/10 [40%], P&#xa0;= 0.04). There were no significant differences in early or late complications.<br><br>CONCLUSIONS: Exposure to anti-VEGF may influence postoperative wound healing and capsule formation which may improve glaucoma tube surgical outcomes. Prospective data is needed to consider perioperative administration of anti-VEGF for glaucoma tube surgery.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38266500,
year = {2024},
author = {Clemens, CR and Eter, N and Alten, F},
title = {Current Perspectives on Type 3 Macular Neovascularization due to Age-Related Macular Degeneration.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {2},
pages = {73-84},
pmid = {38266500},
issn = {1423-0267},
mesh = {Humans ; *Fluorescein Angiography/methods ; Fundus Oculi ; Macula Lutea/pathology ; *Macular Degeneration/diagnosis/complications/etiology ; Retinal Pigment Epithelium/pathology ; *Tomography, Optical Coherence/methods ; Wet Macular Degeneration/diagnosis ; },
abstract = {BACKGROUND: The aim of this review was to systematically summarize the current knowledge on type 3 macular neovascularization (MNV3) in age-related macular degeneration (AMD).<br><br>SUMMARY: Recent histopathologic and multimodal imaging findings led to the consensus definition of the new term "type 3 macular neovascularization" in AMD. MNV3 originates in the deep vascular plexus as a neovascular process without connection with the retinal pigment epithelium in the initial stages. This type has numerous clinical and pathomorphologic features that separate it from the other two types of MNV in AMD. Besides, its frequency appears to be higher than previously thought. In optical coherence tomography (OCT), MNV3 can be classified into stages 1-3. Hyperreflective foci in the outer retina possibly represent a precursor lesion. In addition, MNV3 is characterized by a strong association with reticular pseudodrusen, a high rate of bilaterality, close associations with advanced age and arterial hypertension, decreased choroidal thickness, and decreased choriocapillaris flow signals. Data from latest anti-vascular endothelial growth factor studies in MNV3 suggest that the OCT biomarkers in intraretinal and subretinal fluids should be interpreted differently than in the other types. Additionally, data from MNV3 eyes should be analyzed separately, allowing optimal type-specific treatment strategies in the future.<br><br>KEY MESSAGES: This review highlights the need for accurate characterization of neovascular AMD lesions and an MNV type-specific approach, particularly for MNV3.},
}
@article {pmid38266105,
year = {2024},
author = {Zekavat, SM and Jorshery, SD and Rauscher, FG and Horn, K and Sekimitsu, S and Koyama, S and Nguyen, TT and Costanzo, MC and Jang, D and Burtt, NP and Kühnapfel, A and Shweikh, Y and Ye, Y and Raghu, V and Zhao, H and Ghassemi, M and Elze, T and Segrè, AV and Wiggs, JL and Del Priore, L and Scholz, M and Wang, JC and Natarajan, P and Zebardast, N},
title = {Phenome- and genome-wide analyses of retinal optical coherence tomography images identify links between ocular and systemic health.},
journal = {Science translational medicine},
volume = {16},
number = {731},
pages = {eadg4517},
doi = {10.1126/scitranslmed.adg4517},
pmid = {38266105},
issn = {1946-6242},
support = {K23 EY032634/EY/NEI NIH HHS/United States ; R01 EY020928/EY/NEI NIH HHS/United States ; R01 EY022305/EY/NEI NIH HHS/United States ; R01 EY031820/EY/NEI NIH HHS/United States ; R01 EY032559/EY/NEI NIH HHS/United States ; P30 EY014104/EY/NEI NIH HHS/United States ; R01 EY031424/EY/NEI NIH HHS/United States ; R01 HL001427/HL/NHLBI NIH HHS/United States ; R01 HL148565/HL/NHLBI NIH HHS/United States ; R01 HL148050/HL/NHLBI NIH HHS/United States ; F30 HL149180/HL/NHLBI NIH HHS/United States ; R21 EY030631/EY/NEI NIH HHS/United States ; R01 EY030575/EY/NEI NIH HHS/United States ; P30 EY003790/EY/NEI NIH HHS/United States ; },
mesh = {Adult ; Humans ; *Genome-Wide Association Study ; Tomography, Optical Coherence ; Face ; Retina/diagnostic imaging ; *Cardiovascular Diseases ; },
abstract = {The human retina is a multilayered tissue that offers a unique window into systemic health. Optical coherence tomography (OCT) is widely used in eye care and allows the noninvasive, rapid capture of retinal anatomy in exquisite detail. We conducted genotypic and phenotypic analyses of retinal layer thicknesses using macular OCT images from 44,823 UK Biobank participants. We performed OCT layer cross-phenotype association analyses (OCT-XWAS), associating retinal thicknesses with 1866 incident conditions (median 10-year follow-up) and 88 quantitative traits and blood biomarkers. We performed genome-wide association studies (GWASs), identifying inherited genetic markers that influence retinal layer thicknesses and replicated our associations among the LIFE-Adult Study (N = 6313). Last, we performed a comparative analysis of phenome- and genome-wide associations to identify putative causal links between retinal layer thicknesses and both ocular and systemic conditions. Independent associations with incident mortality were detected for thinner photoreceptor segments (PSs) and, separately, ganglion cell complex layers. Phenotypic associations were detected between thinner retinal layers and ocular, neuropsychiatric, cardiometabolic, and pulmonary conditions. A GWAS of retinal layer thicknesses yielded 259 unique loci. Consistency between epidemiologic and genetic associations suggested links between a thinner retinal nerve fiber layer with glaucoma, thinner PS with age-related macular degeneration, and poor cardiometabolic and pulmonary function with a thinner PS. In conclusion, we identified multiple inherited genetic loci and acquired systemic cardio-metabolic-pulmonary conditions associated with thinner retinal layers and identify retinal layers wherein thinning is predictive of future ocular and systemic conditions.},
}
@article {pmid38265052,
year = {2024},
author = {Kim, Y and Song, MY and Han, K and Kim, JH},
title = {Bilateral Involvement of Age-Related Macular Degeneration in South Korea: Findings from the Korea National Health and Nutrition Examination Survey 2017-2020.},
journal = {Ophthalmic epidemiology},
volume = {31},
number = {5},
pages = {460-467},
doi = {10.1080/09286586.2023.2301583},
pmid = {38265052},
issn = {1744-5086},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Age Factors ; Age of Onset ; Cross-Sectional Studies ; *Eye/pathology ; *Functional Laterality ; Incidence ; *Macular Degeneration/epidemiology/pathology ; Nutrition Surveys ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Visual Acuity ; },
abstract = {PURPOSE: To evaluate the bilateral involvement of age-related macular degeneration (AMD) in South Koreans.<br><br>METHODS: This was a cross-sectional study of the Korean National Health and Nutrition Examination Survey (2017-2020). This study included 13,737 participants aged 40&#x2009;years or older. Participants were evaluated to determine the prevalence of bilateral early and late AMD. In cases in which exudative AMD or geographic atrophy (GA) was diagnosed in a single eye, the fellow eye was evaluated to determine the presence and type of late AMD.<br><br>RESULTS: The overall prevalence of bilateral AMD was 6.12% (95% confidence interval [CI], 5.63-6.61). The prevalence of bilateral early AMD was 5.71% (95% CI, 5.24-6.18), while that of late AMD was 0.14% (95% CI, 0.08-0.20). The prevalence of the bilateral involvement of late AMD increased with age. A 0.02% prevalence (95% CI, 0.00-0.06) of late AMD was observed in participants aged 50-59. The prevalence increased to 0.08% (95% CI, 0.00-0.18) in participants aged 60-69, while the prevalence in participants aged 70-79 and over 80 was 0.45% (95% CI, 0.12-0.78) and 1.97% (95% CI, 0.75-3.19), respectively. The prevalence of early AMD in one eye and late AMD in the fellow eye was 0.26% (95% CI, 0.16-0.36).<br><br>CONCLUSIONS: An assessment of the incidence of AMD revealed that a significant number of persons had bilateral involvement. The treatment burden may significantly increase for participants with bilateral late AMD compared to those with unilateral involvement. Therefore, the study may be helpful with the establishment of private and national insurance policies.},
}
@article {pmid38264613,
year = {2023},
author = {Ahmed, CM and Patel, AP and Johnson, HM and Ildefonso, CJ and Lewin, AS},
title = {Suppressor of cytokine signaling 3-derived peptide as a therapeutic for inflammatory and oxidative stress-induced damage to the retina.},
journal = {Molecular vision},
volume = {29},
number = {},
pages = {338-356},
pmid = {38264613},
issn = {1090-0535},
support = {S10 OD028476/OD/NIH HHS/United States ; },
mesh = {Humans ; Animals ; Mice ; Lipopolysaccharides ; Paraquat ; Retina ; Oxidative Stress ; *Retinal Diseases ; *Macular Degeneration ; Peptides ; Inflammation ; Tight Junction Proteins ; Cytokines ; *Iodates ; },
abstract = {PURPOSE: Inflammation and oxidative stress contribute to age-related macular degeneration (AMD) and other retinal diseases. We tested a cell-penetrating peptide from the kinase inhibitory region of an intracellular checkpoint inhibitor suppressor of cytokine signaling 3 (R9-SOCS3-KIR) peptide for its ability to blunt the inflammatory or oxidative pathways leading to AMD.<br><br>METHODS: We used anaphylatoxin C5a to mimic the effect of activated complement, lipopolysaccharide (LPS), and tumor necrosis factor alpha (TNF&#x3b1;) to stimulate inflammation and paraquat to induce mitochondrial oxidative stress. We used a human retinal pigment epithelium (RPE) cell line (ARPE-19) as proliferating cells and a mouse macrophage cell line (J774A.1) to follow cell propagation using microscopy or cell titer assays. We evaluated inflammatory pathways by monitoring the nuclear translocation of NF-&#x3ba;B p65 and mitogen-activated protein kinase p38. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to evaluate the induction of inflammatory markers. In differentiated ARPE-19 monolayers, we evaluated the integrity of tight junction proteins through microscopy and the measurement of transepithelial electrical resistance (TEER). We used intraperitoneal injection of sodium iodate in mice to test the ability of R9-SOC3-KIR to prevent RPE and retinal injury, as assessed by fundoscopy, optical coherence tomography, and histology.<br><br>RESULTS: R9-SOCS3-KIR treatment suppressed C5a-induced nuclear translocation of the NF-kB activation domain p65 in undifferentiated ARPE-19 cells. TNF-mediated damage to tight junction proteins in RPE, and the loss of TEER was prevented in the presence of R9-SOCS3-KIR. Treatment with the R9-SOCS3-KIR peptide blocked the C5a-induced expression of inflammatory genes. The R9-SOCS3-KIR treatment also blocked the LPS-induced expression of interleukin-6, MCP1, cyclooxygenase 2, and interleukin-1 beta. R9-SOCS3-KIR prevented paraquat-mediated cell death and enhanced the levels of antioxidant effectors. Daily eye drop treatment with R9-SOCS3-KIR protected against retinal injury caused by i.p. administration of sodium iodate.<br><br>CONCLUSIONS: R9-SOCS3-KIR blocks the induction of inflammatory signaling in cell culture and reduces retinal damage in a widely used RPE/retinal oxidative injury model. As this peptide can be administered through corneal instillation, this treatment may offer a convenient way to slow down the progression of ocular diseases arising from inflammation and chronic oxidative stress.},
}
@article {pmid38261803,
year = {2024},
author = {Servillo, A and Kesim, C and Sacconi, R and Battista, M and Capuano, V and Fragiotta, S and Querques, L and Parravano, M and Souied, EH and Bandello, F and Querques, G},
title = {NONEXUDATIVE INTRARETINAL FLUID IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {6},
pages = {997-1005},
doi = {10.1097/IAE.0000000000004054},
pmid = {38261803},
issn = {1539-2864},
mesh = {Humans ; Aged ; Female ; Male ; Aged, 80 and over ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Subretinal Fluid ; *Visual Acuity/physiology ; *Multimodal Imaging ; Macular Degeneration/diagnosis/physiopathology ; Indocyanine Green/administration &amp; dosage ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: To describe the occurrence of nonexudative intraretinal fluid (IRF) in intermediate age-related macular degeneration.<br><br>METHODS: A retrospective study was designed to include consecutive cases with intermediate age-related macular degeneration associated with IRF. A multimodal imaging approach was used to confirm diagnosis of IRF in intermediate age-related macular degeneration. Multimodal imaging included color fundus photograph, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography.<br><br>RESULTS: Ten eyes of 10 patients (2 male and 8 female patients, ages 68-80 years) showing IRF in intermediate age-related macular degeneration were included in the study. The mean best-corrected visual acuity was 20/40 Snellen equivalent. Multimodal imaging including fluorescein angiography/indocyanine green angiography and optical coherence tomography demonstrated the absence of macular neovascularization in all cases; optical coherence tomography-angiography did not detect any abnormal flow signal associated with IRF. Seven of 10 patients developed IRF in correspondence of pigment epithelium detachment. Three of 10 patients presented IRF in correspondence of an area of nascent geographic atrophy.<br><br>CONCLUSION: Nonexudative intraretinal fluid in intermediate age-related macular degeneration is a novel, distinctive feature that is characterized by the presence of IRF with no evidence of macular neovascular lesions. The authors described different phenotypes of IRF in intermediate age-related macular degeneration. The definite diagnosis of this condition requires further studies with thorough application of multimodal imaging.},
}
@article {pmid38260506,
year = {2024},
author = {Strobl, EV and Gamazon, ER},
title = {Discovering Root Causal Genes with High Throughput Perturbations.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38260506},
issn = {2692-8205},
support = {R01 HG011138/HG/NHGRI NIH HHS/United States ; R35 HG010718/HG/NHGRI NIH HHS/United States ; },
abstract = {Root causal gene expression levels - or root causal genes for short - correspond to the initial changes to gene expression that generate patient symptoms as a downstream effect. Identifying root causal genes is critical towards developing treatments that modify disease near its onset, but no existing algorithms attempt to identify root causal genes from data. RNA-sequencing (RNA-seq) data introduces challenges such as measurement error, high dimensionality and non-linearity that compromise accurate estimation of root causal effects even with state-of-the-art approaches. We therefore instead leverage Perturb-seq, or high throughput perturbations with single cell RNA-seq readout, to learn the causal order between the genes. We then transfer the causal order to bulk RNA-seq and identify root causal genes specific to a given patient for the first time using a novel statistic. Experiments demonstrate large improvements in performance. Applications to macular degeneration and multiple sclerosis also reveal root causal genes that lie on known pathogenic pathways, delineate patient subgroups and implicate a newly defined omnigenic root causal model.},
}
@article {pmid38260144,
year = {2023},
author = {Choi, KE and Joung, C and Pahk, KJ and Kim, H and Pahk, K},
title = {Metabolic activity of visceral adipose tissue is associated with age-related macular degeneration: a pilot [18]F-FDG PET/CT study.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1322326},
pmid = {38260144},
issn = {1664-2392},
mesh = {Aged ; Humans ; *Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Angiogenesis Inhibitors ; Intra-Abdominal Fat/diagnostic imaging ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Inflammation ; Obesity/complications/diagnostic imaging ; Biomarkers ; },
abstract = {BACKGROUND: Obesity is known to increase the risk and severity of age-related macular degeneration (AMD). Increased inflamed metabolic activity of visceral adipose tissue (VAT) is considered as a crucial underlying mechanism for the harmful effects of obesity. In this study, we aimed to investigate the inflamed metabolic activity of VAT with [18]F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and their association with AMD.<br><br>MATERIALS AND METHODS: A total of 57 elderly participants (aged &#x2265; 50 years) who underwent [18]F-FDG PET/CT for health screening and subsequent fundoscopic exam for complaint of recently impaired vision were enrolled. The metabolic activity of VAT was measured from the maximum standardized uptake value (SUVmax) of VAT. The early AMD participant was defined as the participant with either eye satisfying AMD and without any sign of advanced AMD (neovascular AMD or geographic atrophy). The late AMD participant was defined as the participant with either eye satisfying advanced AMD.<br><br>RESULTS: VAT SUVmax was highest in participants with late AMD, intermediate in early AMD, and lowest in non-AMD participants. The levels of systemic inflammation surrogate markers were also highest in late AMD group. Furthermore, VAT SUVmax was positively correlated with systemic inflammation surrogate markers and independently associated with the late AMD.<br><br>CONCLUSIONS: The metabolic activity of VAT evaluated by [18]F-FDG PET/CT was associated with the severity of AMD and synchronized with the level of systemic inflammation. Thus, VAT SUVmax could be potentially employed as a surrogate marker of obesity-driven VAT inflammation associated with AMD.},
}
@article {pmid38259505,
year = {2023},
author = {Lei, S and Hu, M and Wei, Z},
title = {Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration.},
journal = {Frontiers in cellular neuroscience},
volume = {17},
number = {},
pages = {1322451},
pmid = {38259505},
issn = {1662-5102},
abstract = {PURPOSE: To investigate the role of senescence-related cytokines (SRCs) in the pathophysiology of age-related macular degeneration (AMD).<br><br>DESIGN: The whole study is based on single-cell and bulk tissue transcriptomic analysis of the human neuroretinas with or without AMD. The transcriptomic data of human neuroretinas was obtained from Gene-Expression Omnibus (GEO) database.<br><br>METHODS: For single-cell transcriptomic analysis, the gene expression matrix goes through quality control (QC) filtering, being normalized, scaled and integrated for downstream analysis. The further analyses were performed using Seurat R package and CellChat R package. After cell type annotation, the expression of phenotype and functional markers of microglia was investigated and cell-cell communication analysis was performed. For bulk tissue transcriptomic analysis, GSE29801 dataset contains the transcriptomic data of human macular neuroretina (n = 118) from control group and AMD patients. The expression of SPP1 in control and AMD subtypes were compared by Student's t-test. In addition, the AMD macular neuroretina were classified into SPP1-low and SPP1-high groups according to the expression level of SPP1. The differentially expressed genes between these two groups were subsequently identified and the pathway enrichment analysis for these genes was further conducted.<br><br>RESULTS: Secreted phosphoprotein 1, as an SRC, was revealed to be highly expressed in microglia of AMD neuroretina and the SPP1-receptor signaling was highly activated in AMD neuroretina. In addition, SPP1 signaling was associated with the pro-inflammatory phenotype and phagocytic state of microglia. SPP1 expression was elevated in macular neuroretina with late dry and wet AMD and the inflammatory pathways were found to be activated in SPP1-high AMD macular neuroretina.<br><br>CONCLUSION: Our findings indicated that SPP1 and microglial activation might play an important role in the pathophysiology of AMD. Therefore, SPP1 might serve as a potential therapeutic target for AMD. More in vitro and in vivo studies are required to confirm the results and the therapeutic effect of SPP1-targeting strategy.},
}
@article {pmid38259182,
year = {2024},
author = {Khanna, S and Shaw, L and Hyman, MJ and Zhang, J and Hariprasad, S and Soo, J and Flores, A and Skondra, D},
title = {ASSOCIATION OF METFORMIN USE WITH RISK OF NEWLY ONSET NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEVELOPMENT.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {2},
pages = {205-213},
doi = {10.1097/IAE.0000000000003968},
pmid = {38259182},
issn = {1539-2864},
support = {//Bucksbaum Institute for Clinical Excellence/ ; },
mesh = {Humans ; *Diabetic Retinopathy/epidemiology ; Angiogenesis Inhibitors ; Case-Control Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; *Metformin/therapeutic use ; Methyldopa ; },
abstract = {PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD).<br><br>METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed.<br><br>RESULTS: Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g.<br><br>CONCLUSION: Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.},
}
@article {pmid38259133,
year = {2024},
author = {Siddiqui, MZ and Elhusseiny, AM and Soliman, MK and Chauhan, MZ and Neuhouser, AJ and Yang, YC and Sallam, AB},
title = {Intraoperative complications and visual outcomes of cataract surgery in neovascular age-related macular degeneration.},
journal = {Journal of cataract and refractive surgery},
volume = {50},
number = {2},
pages = {140-145},
doi = {10.1097/j.jcrs.0000000000001325},
pmid = {38259133},
issn = {1873-4502},
mesh = {Humans ; *Cataract ; Intraoperative Complications ; *Lens, Crystalline ; *Macular Degeneration ; Retrospective Studies ; },
abstract = {PURPOSE: To compare the rate of intraoperative complications and visual outcomes in patients with neovascular age-related macular degeneration (NvAMD) and control eyes without NvAMD undergoing phacoemulsification.<br><br>SETTING: Multicenter study.<br><br>DESIGN: Retrospective, nonrandomized comparative study.<br><br>METHODS: Eyes were classified based on the presence or absence of an NvAMD diagnosis. The main outcomes were (1) the rate of intraoperative complications, (2) the logMAR visual acuity (VA) at 4 to 12 weeks postoperatively in both groups, and (3) the reinjection rate of intravitreal antivascular endothelial growth factor after phacoemulsification.<br><br>RESULTS: Preoperative VA was worse in the NvAMD group (0.9 &#xb1; 0.5) compared with the reference group (0.6 &#xb1; 0.5). We observed no difference in the rate of posterior capsule rupture (PCR) (2.90% vs 2.77%; P = .889), dropped lens fragments (0.46% vs 0.29%; P = .618), or zonular dialysis (0.46% vs 0.58%, P = .749) between the 2 groups. Receiving &#x2265;10 intravitreal injections before cataract surgery predicted the likelihood of PCR with an odds ratio of 2.86 (P = .027). Proportions of eyes achieving a visual gain of &#x2265;0.3 logMAR (&#x223c;3 Snellen lines equivalent) was lower in NvAMD eyes (39.2% vs 63.7%; P < .0001). We observed 203 eyes (73%) in the active treatment group and 139 eyes (36%) in the inactive treatment group received >1 intravitreal injection after phacoemulsification (P < .0001).<br><br>CONCLUSIONS: The risk for PCR was higher for eyes receiving &#x2265;10 intravitreal injections before phacoemulsification. Only 39% of eyes with NvAMD had visual improvement by &#x2265;3 Snellen lines.},
}
@article {pmid38258115,
year = {2024},
author = {García-Quintanilla, L and Almuiña-Varela, P and Rodríguez-Cid, MJ and Gil-Martínez, M and Abraldes, MJ and Gómez-Ulla, F and González-Barcia, M and Mondelo-García, C and Estany-Gestal, A and Otero-Espinar, FJ and Fernández-Rodríguez, M and Fernández-Ferreiro, A},
title = {The Effect of Systemic Parameters and Baseline Characteristics in Short-Term Response Analysis with Intravitreal Ranibizumab in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Pharmaceutics},
volume = {16},
number = {1},
pages = {},
pmid = {38258115},
issn = {1999-4923},
support = {PI17/00940//Instituto de Salud Carlos III/ ; IN607D 2021/001//Xunta de Galicia/ ; },
abstract = {Anti-vascular endothelial growth factor drugs keep being the main therapy for neovascular age-related macular degeneration (AMD). Possible predictive parameters (demographic, biochemical and/or inflammatory) could anticipate short-term treatment response with ranibizumab. 46 treatment-naive patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD and the clinical examination was made at baseline and one month after the third injection. Demographic characteristics, co-morbidities and concomitant treatments were recorded at the baseline visit. Biochemical parameters, complete blood count and inflammation biomarkers were also measured at these times. Uric Acid was found to be statistically significant with a one-point difference between good and poor responders in both basal and treated patients, but only in basal parameters was statistical significance reached (p = 0.007 vs. p = 0.071 in treated patients). Cholesterol and inflammatory parameters such as white blood cell count and neutrophils were significantly reduced over time when treated with intravitreal ranibizumab. On the other hand, women seemed to have a worse prognosis for short-term response to intravitreal ranibizumab treatment. Uric acid may help identify possible non-responders before initial treatment with ranibizumab, and cholesterol and white blood cells could be good candidates to monitor short-term response to ranibizumab treatment.},
}
@article {pmid38256517,
year = {2024},
author = {Hara, C and Suzue, M and Fujimoto, S and Fukushima, Y and Sayanagi, K and Nishida, K and Maruyama, K and Sato, S and Nishida, K},
title = {Comparison of Loading Dose between Aflibercept and Faricimab for Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {2},
pages = {},
pmid = {38256517},
issn = {2077-0383},
abstract = {BACKGROUND: Recently, faricimab was approved as the new drug for neovascular age-related macular degeneration (nAMD). We lack the knowledge to choose between the existing drug and this new drug to use for treatment-naïve nAMD cases. In this study, we compared the functional and morphologic effects in loading dose between patients with treatment-naïve nAMD treated with either intravitreal aflibercept (IVA) or intravitreal faricimab (IVF) injection in a clinical setting.<br><br>METHOD: This retrospective study included 30 eyes of 28 patients who started treatment with IVA between June and September 2022 and 30 eyes of 29 patients who were administered IVF between October 2022 and March 2023. All patients received three monthly IVA or IVF. The best corrected visual acuity (BCVA), central retinal thickness (CRT), and the proportion of eyes with residual exudative change at baseline and 1,2, and 3 months after initial treatment were compared between the groups.<br><br>RESULTS: The mean BCVA significantly improved from pre-treatment after the loading dose in the IVA group (0.46 &#xb1; 0.46-0.36 &#xb1; 0.37, p = 0.0047) but not in the IVF group (0.46 &#xb1; 0.41-0.44 &#xb1; 0.45, p = 0.60). The mean CRT significantly improved in both groups. The proportion of eyes with residual exudative change was greater in the IVF group than in the IVA group 2 months after the first treatment (p = 0.026). The analysis of cases that achieved complete resolution of exudative changes after the loading dose showed that the IVA group had a significant improvement in the BCVA, whereas the IVF group did not (p = 0.0047 and 0.20, respectively).<br><br>CONCLUSIONS: Although both IVA and IVF significantly improved CRT, the BCVA improved significantly in the IVA group but not in the IVF group.},
}
@article {pmid38256501,
year = {2024},
author = {Confalonieri, F and Ferraro, V and Barone, G and Di Maria, A and Petrovski, B&#xc9; and Vallejo Garcia, JL and Randazzo, A and Vinciguerra, P and Lumi, X and Petrovski, G},
title = {Outcomes in the Treatment of Subretinal Macular Hemorrhage Secondary to Age-Related Macular Degeneration: A Systematic Review.},
journal = {Journal of clinical medicine},
volume = {13},
number = {2},
pages = {},
pmid = {38256501},
issn = {2077-0383},
abstract = {Background: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood collection between the neurosensory retina and the retinal pigment epithelium (RPE). Without prompt treatment, visual prognosis is poor. A plethora of treatment approaches have been tried over the past years ranging from intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy to direct subretinal surgery, with no conclusive superiority of one over the other. Materials and Methods: We conducted a systematic review of the outcomes and treatment modalities of SRMH from inception to 14 June 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence was assessed for all included articles according to the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A total of 2745 articles were initially extracted, out of which 1654 articles were obtained after duplicates were removed and their abstracts screened. A total of 155 articles were included for full-text review. Finally, 81 articles remained that fulfilled the inclusion criteria. Conclusions: Even though there are solid results supporting a variety of treatments for SRMH, the best treatment modality has still not been conclusively demonstrated and further research is needed.},
}
@article {pmid38256192,
year = {2024},
author = {Tempone, MH and Borges-Martins, VP and César, F and Alexandrino-Mattos, DP and de Figueiredo, CS and Raony, &#xcd; and Dos Santos, AA and Duarte-Silva, AT and Dias, MS and Freitas, HR and de Araújo, EG and Ribeiro-Resende, VT and Cossenza, M and P Silva, H and P de Carvalho, R and Ventura, ALM and Calaza, KC and Silveira, MS and Kubrusly, RCC and de Melo Reis, RA},
title = {The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.},
journal = {International journal of molecular sciences},
volume = {25},
number = {2},
pages = {},
pmid = {38256192},
issn = {1422-0067},
support = {E-26/202.668/2018//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; 312157/2016-9//National Council for Scientific and Technological Development/ ; E-26/010.002215/2019//Funda&#xe7;&#xe3;o Carlos Chagas Filho de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; },
mesh = {Animals ; Humans ; Blindness ; Health Status ; Neuroglia ; Neurons ; Retina ; *Retinal Diseases ; },
abstract = {The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.},
}
@article {pmid38255252,
year = {2024},
author = {Stout, JA and Mahzarnia, A and Dai, R and Anderson, RJ and Cousins, S and Zhuang, J and Lad, EM and Whitaker, DB and Madden, DJ and Potter, GG and Whitson, HE and Badea, A},
title = {Accelerated Brain Atrophy, Microstructural Decline and Connectopathy in Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {12},
number = {1},
pages = {},
pmid = {38255252},
issn = {2227-9059},
support = {RF1 AG057895/AG/NIA NIH HHS/United States ; R01 AG043438/AG/NIA NIH HHS/United States ; R01 AG043438/NH/NIH HHS/United States ; RF1 AG070149/AG/NIA NIH HHS/United States ; P30 AG028716/NH/NIH HHS/United States ; RF1 AG070149/NH/NIH HHS/United States ; RF1 AG057895/NH/NIH HHS/United States ; P30 AG072978/NH/NIH HHS/United States ; R01 AG066184/AG/NIA NIH HHS/United States ; R01 AG039684/AG/NIA NIH HHS/United States ; R01 AG039684/NH/NIH HHS/United States ; P30 AG072958/AG/NIA NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; R01 AG066184/NH/NIH HHS/United States ; P30 AG072958/NH/NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) has recently been linked to cognitive impairment. We hypothesized that AMD modifies the brain aging trajectory, and we conducted a longitudinal diffusion MRI study on 40 participants (20 with AMD and 20 controls) to reveal the location, extent, and dynamics of AMD-related brain changes. Voxel-based analyses at the first visit identified reduced volume in AMD participants in the cuneate gyrus, associated with vision, and the temporal and bilateral cingulate gyrus, linked to higher cognition and memory. The second visit occurred 2 years after the first and revealed that AMD participants had reduced cingulate and superior frontal gyrus volumes, as well as lower fractional anisotropy (FA) for the bilateral occipital lobe, including the visual and the superior frontal cortex. We detected faster rates of volume and FA reduction in AMD participants in the left temporal cortex. We identified inter-lingual and lingual-cerebellar connections as important differentiators in AMD participants. Bundle analyses revealed that the lingual gyrus had a lower streamline length in the AMD participants at the first visit, indicating a connection between retinal and brain health. FA differences in select inter-lingual and lingual cerebellar bundles at the second visit showed downstream effects of vision loss. Our analyses revealed widespread changes in AMD participants, beyond brain networks directly involved in vision processing.},
}
@article {pmid38254230,
year = {2024},
author = {Lima, LH and Braga, JPR and Melo, GB and Cella, WP and Brandão, ASL and Meirelles, RL and Zett, C and Cyrino, FVR and Jorge, R},
title = {Serous maculopathy with absence of retinal pigment epithelium (SMARPE) associated with large drusen.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {8},
pmid = {38254230},
issn = {2056-9920},
abstract = {PURPOSE: To describe the association of serous maculopathy with absence of retinal pigment epithelium (SMARPE) and large drusen in patients with non-neovascular age-related macular degeneration (AMD).<br><br>METHODS: A retrospective study of ophthalmic examination and multimodal imaging data of individuals with SMARPE and large drusen observed over a period of 12-month was accomplished. SMARPE was defined as subretinal accumulation of fluid within the macular area due to retinal pigment epithelium (RPE) aperture. Large drusen were identified by the presence of sub-RPE deposits using multimodal imaging analysis (color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography).<br><br>RESULTS: Twelve eyes of 7 white patients with a mean age of 77 years were observed to have SMARPE associated with large drusen. The median visual acuity was 20/100. Bilateral SMARPE lesions were observed in 71% of study patients. All SMARPE lesions were hypoautofluorescent, located in the subretinal space between the RPE and the ellipsoid zone, and presented as complete or incomplete RPE apertures associated with subretinal fluid. The SMARPE in this study had coincident multimodal imaging features as the SMARPE described in other reports in the literature.<br><br>CONCLUSIONS: Bilateral SMARPE can occur in association with typical AMD large drusen. Anomalisms resulting in drusen biogenesis or mechanisms that act alongside to these may be related to SMARPE development.},
}
@article {pmid38254006,
year = {2024},
author = {Källstrand, J and Lindgren, EC and Carlsson, IM},
title = {Perpetuating ability to live life as usual: a grounded theory study of persons living with age-related macular degeneration.},
journal = {BMC geriatrics},
volume = {24},
number = {1},
pages = {82},
pmid = {38254006},
issn = {1471-2318},
support = {NYPS - 20293225//Interreg &#xd6;resund- Kattegat-Skagerrak European Regional Development Fund/ ; NYPS - 20293225//Interreg &#xd6;resund- Kattegat-Skagerrak European Regional Development Fund/ ; NYPS - 20293225//Interreg &#xd6;resund- Kattegat-Skagerrak European Regional Development Fund/ ; F 2020/111//School of Health and Welfare, Halmstad University/ ; F 2020/111//School of Health and Welfare, Halmstad University/ ; F 2020/111//School of Health and Welfare, Halmstad University/ ; },
mesh = {Humans ; Aged ; Grounded Theory ; *Macular Degeneration/diagnosis/epidemiology ; Eye ; Aging ; Emotions ; },
abstract = {BACKGROUND: Age-Related Macular Degeneration (AMD) is an eye disease associated with age that causes progressive and irreversible loss of central vision, while the peripheral visual ability remains. The occurrence of and especially late AMD is estimated to increase extensively to 2040 among persons aged ≥ 65 in Scandinavia, due to an increasing aging population.<br><br>OBJECTIVES: The present study explored what it means to live with AMD through the eyes of those living with the condition.<br><br>METHODS: This is an explorative interview study. People who were&#x2009;&#x2265;&#x2009;65&#xa0;years old, living in their own homes, and diagnosed with advanced dry AMD in one or both eyes, causing a visual acuity of no more than 0.3 or worse in the best eye, were invited to participate in the study. The method chosen was the constructivist grounded theory, where reality is seen as fundamentally social and processual and a way of accessing the participants' experiences, thoughts, and feelings.<br><br>RESULTS: In total, 12 interviews were conducted. Living with dry AMD confronted different problems and challenges. The substantive theory, Perpetuating ability to live life as usual, is characterised by a desire to continue life as usual, which requires an acceptance of the disease's progress, self-acceptance of the new me, and an acceptance that the new life needs to be lived a little more carefully. Moreover, the participants used three strategies to resolve their main concern by maintaining an everyday life 1) Navigating the new normal, 2) Trusting own ability, and 3) Interdepending.<br><br>CONCLUSION: Maintaining an everyday life is the primary concern among people with AMD. In supporting self-care, gaining information about the subjective experience to support their everyday living is of the utmost importance. This grounded theory captures valuable knowledge of how the older adults resolved their main concern "you got to keep on" despite their affected vision by "facing the fact" live life as usual since since life goes on. Our study also gives rise both to implications for research and practice in order to strengthen older people with AMD facing their future challenges.<br><br>TRIAL REGISTRATION: The Swedish Ethical Review Authority (EPN 2021/02877).},
}
@article {pmid38253888,
year = {2024},
author = {El-Darzi, N and Mast, N and Li, Y and Pikuleva, IA},
title = {APOB100 transgenic mice exemplify how the systemic circulation content may affect the retina without altering retinal cholesterol input.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {81},
number = {1},
pages = {52},
pmid = {38253888},
issn = {1420-9071},
support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 EY018383/EY/NEI NIH HHS/United States ; EY011373/EY/NEI NIH HHS/United States ; EY018383/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Mice ; Animals ; Mice, Transgenic ; *Retina ; Retinal Pigment Epithelium ; Cholesterol ; *Macular Degeneration/genetics ; },
abstract = {Apolipoprotein B (APOB) is a constituent of unique lipoprotein particles (LPPs) produced in the retinal pigment epithelium (RPE), which separates the neural retina from Bruch's membrane (BrM) and choroidal circulation. These LPPs accumulate with age in BrM and contribute to the development of age-related macular degeneration, a major blinding disease. The APOB100 transgenic expression in mice, which unlike humans lack the full-length APOB100, leads to lipid deposits in BrM. Herein, we further characterized APOB100 transgenic mice. We imaged mouse retina in vivo and assessed chorioretinal lipid distribution, retinal sterol levels, retinal cholesterol input, and serum content as well as tracked indocyanine green-bound LPPs in mouse plasma and retina after an intraperitoneal injection. Retinal function and differentially expressed proteins were also investigated. APOB100 transgenic mice had increased serum LDL content and an additional higher density HDL subpopulation; their retinal cholesterol levels (initially decreased) became normal with age. The LPP cycling between the RPE and choroidal circulation was increased. Yet, LPP trafficking from the RPE to the neural retina was limited, and total retinal cholesterol input did not change. There were lipid deposits in the RPE and BrM, and retinal function was impaired. Retinal proteomics provided mechanistic insights. Collectively, our data suggested that the serum LDL/HDL ratio may not affect retinal pathways of cholesterol input as serum LPP load is mainly handled by the RPE, which offloads LPP excess to the choroidal circulation rather than neural retina. Different HDL subpopulations should be considered in studies linking serum LPPs and age-related macular degeneration.},
}
@article {pmid38252904,
year = {2024},
author = {Wang, M and Li, H and Wu, Y and Wang, B and Xi, Y and Hu, K},
title = {Bioinformatics and Network Pharmacology Explore the Role of Immune Cells in the Occurrence of Anti-Vascular Endothelial Growth Factor (VEGF) Resistance in Patients with Neovascular Age-Related Macular Degeneration(nAMD) and the Application of Complementary Medicine Treatment.},
journal = {Ocular immunology and inflammation},
volume = {32},
number = {9},
pages = {1945-1960},
doi = {10.1080/09273948.2024.2306129},
pmid = {38252904},
issn = {1744-5078},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/genetics/metabolism ; *Computational Biology ; *Wet Macular Degeneration/drug therapy/genetics/metabolism ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Superoxide Dismutase-1/genetics/metabolism ; *Drugs, Chinese Herbal/therapeutic use ; *Aqueous Humor/metabolism ; *Network Pharmacology ; Drug Resistance ; Complementary Therapies/methods ; Proteomics ; Male ; Real-Time Polymerase Chain Reaction ; Female ; Retinal Pigment Epithelium/metabolism/drug effects ; Aged ; Medicine, Chinese Traditional/methods ; },
abstract = {PURPOSE: This study explores the immune cells' role in anti-VEGF resistance in nAMD patients, and the potential of Zi-Yin-Jiang-Huo-Tang (ZYJHT), a Traditional Chinese Medicine formula, as complementary therapy.<br><br>METHODS: Aqueous humor proteomics data from 10 nAMD patients with anti-VEGF resistance and 10 nAMD patients without anti-VEGF resistance were analyzed, investigating immune cells's role in anti-VEGF resistance and its underlying mechanism. Network pharmacology methods are employed to analyze the active ingredients in ZYJHT that contribute to therapeutic effects and their mechanisms. Real-time PCR (polymerase chain reaction) was used to detect changes in the expression of SOD1 (superoxide dismutase 1) after treatment with compounds targeting SOD1 in ARPE-19 cells.<br><br>RESULTS: nAMD patients with anti-VEGF resistance showed enhancement of biological processes linked to the positive regulation of immune function, along with decreased cellular resistance to oxidative stress. Infiltration of B cells memory, plasma cells, CD8[+]and &#x3b3;&#x3b4;-T cells were higher in nAMD patients with anti-VEGF resistance. SOD1 was identified as a hub gene in the occurrence of anti-VEGF resistance and a core therapeutic target of ZYJHT, negatively correlated with B and T cell infiltration. Compounds diosgenin, naringenin, and liquiritin in ZYJHT can bind to SOD1 and upregulating SOD1 expression in ARPE-19 cells.},
}
@article {pmid38251411,
year = {2024},
author = {Huang, Y and Zhou, X and Zhang, Y and Xie, M and Wang, F and Qin, J and Ye, H and Zhang, H and Zhang, C and Hong, J},
title = {A Nucleic Acid-Based LYTAC Plus Platform to Simultaneously Mediate Disease-Driven Protein Downregulation.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {11},
number = {13},
pages = {e2306248},
pmid = {38251411},
issn = {2198-3844},
support = {2018YFA0902601//National Key Research and Development Program of China/ ; 2023YFA0915000//National Key Research and Development Program of China/ ; 51973112//National Natural Science Foundation of China/ ; 52225302//National Natural Science Foundation of China/ ; 82171102//National Natural Science Foundation of China/ ; 82271044//National Natural Science Foundation of China/ ; 22Y21900900//Shanghai Medical Innovation Research Program/ ; SHDC2020CR3052B//Shanghai Key Clinical Research Program/ ; 21TQ1400219//Basic Research-Shanghai Jiao Tong University/ ; ZR2022LSW017//Natural Science Foundation of Shandong Province/ ; 23HC1400800//Shanghai Science and Technology Innovation Program/ ; },
mesh = {Mice ; Animals ; *Vascular Endothelial Growth Factor A/genetics ; Down-Regulation ; *Nucleic Acids ; RNA, Small Interfering/genetics ; Hydrogels ; },
abstract = {Protein degradation techniques, such as proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), have emerged as promising therapeutic strategies for the treatment of diseases. However, the efficacy of current protein degradation methods still needs to be improved to address the complex mechanisms underlying diseases. Herein, a LYTAC Plus hydrogel engineered is proposed by nucleic acid self-assembly, which integrates a gene silencing motif into a LYTAC construct to enhance its therapeutic potential. As a proof-of-concept study, vascular endothelial growth factor receptor (VEGFR)-binding peptides and mannose-6 phosphate (M6P) moieties into a self-assembled nucleic acid hydrogel are introduced, enabling its LYTAC capability. Small interference RNAs (siRNAs) is then employed that target the angiopoietin-2 (ANG-2) gene as cross-linkers for hydrogel formation, giving the final LYTAC Plus hydrogel gene silencing ability. With dual functionalities, the LYTAC Plus hydrogel demonstrated effectiveness in simultaneously reducing the levels of VEGFR-2 and ANG-2 both in vitro and in vivo, as well as in improving therapeutic outcomes in treating neovascular age-related macular degeneration in a mouse model. As a general material platform, the LYTAC Plus hydrogel may possess great potential for the treatment of various diseases and warrant further investigation.},
}
@article {pmid38249251,
year = {2023},
author = {Taketani, M and Arakawa, H and Maruko, I and Hasegawa, T and Iida, T},
title = {Characteristics of Eyes With Neovascular Age-Related Macular Degeneration Requiring Frequent Anti-vascular Endothelial Growth Factor Injections.},
journal = {Cureus},
volume = {15},
number = {12},
pages = {e50817},
pmid = {38249251},
issn = {2168-8184},
abstract = {Objective In this study, we aimed to determine the characteristics of neovascular age-related macular degeneration (AMD) patients requiring frequent anti-vascular endothelial growth factor (VEGF) therapy. Methods This was a retrospective observational study involving the review of 32 eyes of 31 patients (25 men and six women, mean age: 74.3 years) treated with anti-VEGF injections for less than eight weeks and at least one year of follow-up. The subtype of macular neovascularization (MNV), follow-up duration, number of injections, visual acuity, and exudative changes during the study period were evaluated. Results Twenty-nine eyes (90.6%) had MNV under the retinal pigment epithelium (RPE), including 11 eyes with type 1 MNV and 18 eyes with polypoidal choroidal vasculopathy (PCV). Only three eyes had type 2 MNV (9.4%) above the RPE. The mean follow-up period was 28.7 ± 16.5 months, and the mean number of injections was 21.5 ± 11.8. The mean visual acuity [logarithm of the minimum angle of resolution (logMAR) units] was 0.19 ± 0.23 at the initial visit to our hospital, which decreased non-significantly to 0.24 ± 0.4 at the final visit (p=0.63). The exudation in four eyes (two with type 1 MNV and two with PCV) never resolved. The exudation remained in 27 eyes (84%) even after every four weeks of treatment, and it was present in five eyes (16%) in the treatment interval of eight weeks. Conclusions In the eyes receiving frequent anti-VEGF injections, the sub-RPE MNV might have affected the response to the treatment. Although patients requiring frequent anti-VEGF therapy did not have a significant decrease in their visual acuity, 84% of the eyes had exudations even with monthly injections.},
}
@article {pmid38247998,
year = {2024},
author = {Li, W and Bian, L and Ma, B and Sun, T and Liu, Y and Sun, Z and Zhao, L and Feng, K and Yang, F and Wang, X and Chan, S and Dou, H and Qi, H},
title = {Interpretable Detection of Diabetic Retinopathy, Retinal Vein Occlusion, Age-Related Macular Degeneration, and Other Fundus Conditions.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
pmid = {38247998},
issn = {2075-4418},
support = {82171022, 81974128,82371026, 82301177//National Natural Science Foundation of China/ ; 2023M730122//China Postdoctoral Science Foundation/ ; BMU2023YFJHPY016//Peking University Medicine Sailing Program for Young Scholars' Scientific &amp; Technological Innovation/ ; },
abstract = {Diabetic retinopathy (DR), retinal vein occlusion (RVO), and age-related macular degeneration (AMD) pose significant global health challenges, often resulting in vision impairment and blindness. Automatic detection of these conditions is crucial, particularly in underserved rural areas with limited access to ophthalmic services. Despite remarkable advancements in artificial intelligence, especially convolutional neural networks (CNNs), their complexity can make interpretation difficult. In this study, we curated a dataset consisting of 15,089 color fundus photographs (CFPs) obtained from 8110 patients who underwent fundus fluorescein angiography (FFA) examination. The primary objective was to construct integrated models that merge CNNs with an attention mechanism. These models were designed for a hierarchical multilabel classification task, focusing on the detection of DR, RVO, AMD, and other fundus conditions. Furthermore, our approach extended to the detailed classification of DR, RVO, and AMD according to their respective subclasses. We employed a methodology that entails the translation of diagnostic information obtained from FFA results into CFPs. Our investigation focused on evaluating the models' ability to achieve precise diagnoses solely based on CFPs. Remarkably, our models showcased improvements across diverse fundus conditions, with the ConvNeXt-base + attention model standing out for its exceptional performance. The ConvNeXt-base + attention model achieved remarkable metrics, including an area under the receiver operating characteristic curve (AUC) of 0.943, a referable F1 score of 0.870, and a Cohen's kappa of 0.778 for DR detection. For RVO, it attained an AUC of 0.960, a referable F1 score of 0.854, and a Cohen's kappa of 0.819. Furthermore, in AMD detection, the model achieved an AUC of 0.959, an F1 score of 0.727, and a Cohen's kappa of 0.686. Impressively, the model demonstrated proficiency in subclassifying RVO and AMD, showcasing commendable sensitivity and specificity. Moreover, our models enhanced interpretability by visualizing attention weights on fundus images, aiding in the identification of disease findings. These outcomes underscore the substantial impact of our models in advancing the detection of DR, RVO, and AMD, offering the potential for improved patient outcomes and positively influencing the healthcare landscape.},
}
@article {pmid38247870,
year = {2024},
author = {Santa Cruz-Pavlovich, FJ and Bolaños-Chang, AJ and Del Rio-Murillo, XI and Aranda-Preciado, GA and Razura-Ruiz, EM and Santos, A and Navarro-Partida, J},
title = {Beyond Vision: An Overview of Regenerative Medicine and Its Current Applications in Ophthalmological Care.},
journal = {Cells},
volume = {13},
number = {2},
pages = {},
pmid = {38247870},
issn = {2073-4409},
mesh = {Humans ; *Ophthalmology ; Regenerative Medicine ; Quality of Life ; Eye ; Cell- and Tissue-Based Therapy ; },
abstract = {Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body's innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology. A search conducted on clinicaltrials.gov unveiled a total of at least 209 interventional trials related to RM within the ophthalmological field. Among these trials, there were numerous early-phase studies, including phase I, I/II, II, II/III, and III trials. Many of these studies demonstrate potential in addressing previously challenging and degenerative eye conditions, spanning from posterior segment pathologies like Age-related Macular Degeneration and Retinitis Pigmentosa to anterior structure diseases such as Dry Eye Disease and Limbal Stem Cell Deficiency. Notably, these therapeutic approaches offer tailored solutions specific to the underlying causes of each pathology, thus allowing for the hopeful possibility of bringing forth a treatment for ocular diseases that previously seemed incurable and significantly enhancing patients' quality of life. As advancements in research and technology continue to unfold, future objectives should focus on ensuring the safety and prolonged viability of transplanted cells, devising efficient delivery techniques, etc.},
}
@article {pmid38244930,
year = {2024},
author = {Smith, RT and Olsen, TW and Chong, V and Kim, J and Hammer, M and Lema, G and Deobhakta, A and Tan, A and Tong, Y and Tai, K and Fei, Y and Mordechaev, E and Ledesma-Gil, G and Otero-Marquez, O and Rosen, RB and Bhuiyan, A and Sivaprasad, S and Rosenfeld, PJ},
title = {Subretinal drusenoid deposits, age-related macular degeneration, and cardiovascular disease.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {1},
pages = {100036},
doi = {10.1016/j.apjo.2024.100036},
pmid = {38244930},
issn = {2162-0989},
mesh = {Humans ; *Retinal Drusen/diagnosis/complications ; *Cardiovascular Diseases/complications/diagnosis ; Tomography, Optical Coherence/methods ; *Macular Degeneration/complications/diagnosis ; *Vascular Diseases/complications ; Fluorescein Angiography ; },
abstract = {Decades of studies on age-related macular degeneration (AMD), cardiovascular disease and stroke have not found consistent associations between AMD and systemic vascular disease. This study suggests that there is in fact no general relationship, but instead a strong, specific association between only the subretinal drusenoid deposit (SDD) phenotype of AMD on retinal imaging and certain co-existent vascular diseases that are high risk for compromised cardiac output or internal carotid artery stenosis. Future screening initiatives for these high -risk vascular diseases (HRVDs) with fast, inexpensive retinal imaging could make a significant contribution to public health and save lives. Likewise, screening patients with known HRVDs for unrecognized AMD of the SDD form could enable needed treatment and save vision.},
}
@article {pmid38244172,
year = {2024},
author = {Matsumoto, H and Hoshino, J and Nakamura, K and Akiyama, H},
title = {One-year results of treat-and-extend regimen with intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {68},
number = {2},
pages = {83-90},
pmid = {38244172},
issn = {1613-2246},
mesh = {Humans ; Treatment Outcome ; Retrospective Studies ; Follow-Up Studies ; Receptors, Vascular Endothelial Growth Factor ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors ; *Wet Macular Degeneration/diagnosis/drug therapy ; Recombinant Fusion Proteins/therapeutic use ; *Antibodies, Bispecific ; },
abstract = {PURPOSE: To evaluate 1-year outcomes of loading phase treatment followed by maintenance therapy using a treat-and-extend (TAE) regimen with intravitreal faricimab for neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective, interventional case series.<br><br>METHODS: We retrospectively studied 40 eyes of 38 consecutive patients with treatment-na&#xef;ve nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), total number of injections over 1 year, and intended injection interval at the last visit.<br><br>RESULTS: Thirty eyes (75.0%) had completed the 1-year intravitreal faricimab treatment. Their BCVA showed significant improvement, with significant reductions in foveal thickness and CCT. The total number of injections during the 1-year treatment period was 6.6&#x2009;&#xb1;&#x2009;0.7. The intended injection interval at the last visit was 12.7&#x2009;&#xb1;&#x2009;3.3 weeks. Of the 10 eyes (25.0%) failing to complete the 1-year faricimab treatment, 1 eye developed intraocular inflammation after the loading phase treatment but showed no recurrence of exudative changes, and no further treatment was required. Moreover, 5 eyes switched to intravitreal brolucizumab injection due to persistent exudative changes with an 8-week interval of faricimab injections. The remaining 4 eyes either dropped out or the patient died.<br><br>CONCLUSIONS: A loading phase treatment followed by a TAE regimen with intravitreal faricimab appears to be generally safe and effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, there might be cases in which exudative changes cannot be adequately controlled with injections of faricimab every 8 weeks in the maintenance phase.},
}
@article {pmid38242423,
year = {2024},
author = {Pollalis, D and Calle, AG and Martinez-Camarillo, JC and Ahluwalia, K and Hinman, C and Mitra, D and Lebkowski, J and Lee, SY and Thomas, BB and Ahmed, F and Chan, V and Junge, JA and Fraser, S and Louie, S and Humayun, M},
title = {Scaling up polarized RPE cell supernatant production on parylene membrane.},
journal = {Experimental eye research},
volume = {240},
number = {},
pages = {109789},
doi = {10.1016/j.exer.2024.109789},
pmid = {38242423},
issn = {1096-0007},
mesh = {Humans ; Animals ; Rats ; *Retinal Pigment Epithelium/metabolism ; Insulin-Like Growth Factor Binding Protein 3/metabolism ; Insulin-Like Growth Factor Binding Protein 4 ; *Retinal Degeneration/metabolism ; *Polymers ; *Xylenes ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss, primarily arises from the degeneration of retinal pigment epithelium (RPE) and photoreceptors. Current therapeutic options for dry AMD are limited. Encouragingly, cultured RPE cells on parylene-based biomimetic Bruch's membrane demonstrate characteristics akin to the native RPE layer. In this study, we cultivated human embryonic stem cell-derived polarized RPE (hESC-PRPE) cells on parylene membranes at both small- and large-scale settings, collecting conditioned supernatant, denoted as PRPE-SF. We conducted a comprehensive analysis of the morphology of the cultured hESC-RPE cells and the secreted growth factors in PRPE-SF. To evaluate the in vivo efficacy of these products, the product was administered via intravitreal injections of PRPE-SF in immunodeficient Royal College of Surgeons (iRCS) rats, a model for retinal degeneration. Our study not only demonstrated the scalability of PRPE-SF production while maintaining RPE cell phenotype but also showed consistent protein concentrations between small- and large-scale batches. We consistently identified 10 key factors in PRPE-SF, including BMP-7, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6, MANF, PEDF, PDGF-AA, TGFβ1, and VEGF. Following intravitreal administration of PRPE-SF, we observed a significant increase in the thickness of the outer nuclear layer (ONL) and photoreceptor preservation in iRCS rats. Furthermore, correlation analysis revealed that IGFBP-3, IGFBP-4, MANF, PEDF, and TGFβ1 displayed positive associations with in vivo bioactivity, while GDF-15 exhibited a negative correlation. Overall, this study highlights the feasibility of scaling up PRPE-SF production on parylene membranes without compromising its essential constituents. The outcomes of PRPE-SF administration in an animal model of retinal degeneration present substantial potential for photoreceptor preservation. Moreover, the identification of candidate surrogate potency markers, showing strong positive associations with in vivo bioactivity, lays a solid foundation for the development of a promising therapeutic intervention for retinal degenerative diseases.},
}
@article {pmid38241770,
year = {2024},
author = {Desmettre, T and Baillif, S and Mathis, T and Gatinel, D and Mainster, M},
title = {[Blue light and intraocular lenses (IOLs): Beliefs and realities].},
journal = {Journal francais d'ophtalmologie},
volume = {47},
number = {2},
pages = {104043},
doi = {10.1016/j.jfo.2023.104043},
pmid = {38241770},
issn = {1773-0597},
mesh = {Humans ; Aged ; Ultraviolet Rays/adverse effects ; Blue Light ; *Lenses, Intraocular/adverse effects ; Light ; *Macular Degeneration/epidemiology/etiology/prevention &amp; control ; Vision Disorders ; *Cataract ; },
abstract = {The first intraocular lenses (IOLs) used for cataract surgery transmitted both ultraviolet (UV) radiation and visible light to the retina. Colorless UV-blocking IOLs were introduced and rapidly adopted in the 1980s. Yellow-tinted blue-blocking (also known as blue-filtering) IOLs were marketed in the early 1990s. Blue-blocking IOLs were intended to simulate age-related crystalline lens yellowing to reduce the cyanopsia that some patients experienced after cataract surgery. When blue-filtering IOLs were introduced in North America, however, blue-blocking chromophores were advocated as a way to protect patients from age-related macular degeneration (AMD) despite the lack of evidence that normal environmental light exposure causes AMD. The "blue light hazard" is a term that describes the experimental finding that acute, abnormally intense light exposures are potentially more phototoxic to the retina when short rather than long wavelengths are used. Thus, in brief exposures to intense light sources such as welding arcs, ultraviolet radiation is more hazardous than blue light, which is more hazardous than longer wavelength green or red light. International commissions have cautioned that the blue light hazard does not apply to normal indoor or outdoor light exposures. Nonetheless, the hazard is used for commercial purposes to suggest misleadingly that ambient environmental light can cause acute retinal phototoxicity and increase the risk of AMD. Very large epidemiological studies show that blue-blocking IOLs do not reduce the risk or progression of AMD. Additionally, blue-filtering IOLs or spectacles cannot decrease glare disability, because they decrease image and glare illuminance in the same proportion. Blue light is essential for older adults' scotopic photoreception needed to reduce the risk of nighttime falling and related injuries. It is also critical for circadian photoreception that is essential for good health, sleep and cognitive performance. Unfortunately, age-related pupillary miosis, retinal rod and ganglion cell photoreceptor degeneration and decreased outdoor activity all reduce the amount of healthful blue light available to older adults. Blue-restricting IOLs further reduce the available blue light at a time when older adults need it most. Patients and ophthalmologists are exposed to hypothesis-based advertisements for blue-filtering optical devices that suppress short wavelength light critical for vision in dim lighting and for good physical and mental health. Spectacle and intraocular lens selections should be based on scientific fact, not conjecture. Ideal IOLs should improve photoreception rather than limit it permanently. Practice efficiency, surgical convenience and physician-manufacturer relationships may eliminate a patient's opportunity to choose between colorless blue-transmitting IOLs and yellow-tinted, blue-restricting IOLs. Cataract surgeons ultimately determine whether their patients have the opportunity to make an informed choice about their future photoreception.},
}
@article {pmid38241545,
year = {2024},
author = {Lin, HY and Chou, W and Chien, TW and Yeh, YT and Kuo, SC and Hsu, SY},
title = {Analyzing shifts in age-related macular degeneration research trends since 2014: A bibliometric study with triple-map Sankey diagrams (TMSD).},
journal = {Medicine},
volume = {103},
number = {3},
pages = {e36547},
pmid = {38241545},
issn = {1536-5964},
mesh = {Humans ; Aged ; *Macular Degeneration ; Retina ; Academies and Institutes ; Algorithms ; Bibliometrics ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the primary cause of vision impairment in older adults, especially in developed countries. While many articles on AMD exist in the literature, none specifically delve into the trends based on document categories. While bibliometric studies typically use dual-map overlays to highlight new trends, these can become congested and unclear with standard formats (e.g., in CiteSpace software). In this study, we introduce a unique triple-map Sankey diagram (TMSD) to assess the evolution of AMD research. Our objective is to understand the nuances of AMD articles and show the effectiveness of TMSD in determining whether AMD research trends have shifted over the past decade.<br><br>METHODS: We collected 7465 articles and review pieces related to AMD written by ophthalmologists from the Web of Science core collection, accumulating article metadata from 2014 onward. To delve into the characteristics of these AMD articles, we employed various visualization methods, with a special focus on TMSD to track research evolution. We adopted the descriptive, diagnostic, predictive, and prescriptive analytics (DDPP) model, complemented by the follower-leading clustering algorithm (FLCA) for clustering analysis. This synergistic approach proved efficient in identifying and showcasing research focal points and budding trends using network charts within the DDPP framework.<br><br>RESULTS: Our findings indicate that: in countries, institutes, years, authors, and journals, the dominant entities were the United States, the University of Bonn in Germany, the year 2021, Dr Jae Hui Kim from South Korea, and the journal "Retina"; in accordance with the TMSD, AMD research trends have not changed significantly since 2014, as the top 4 categories for 3 citing, active, and cited articles have not changed, in sequence (Ophthalmology, Science &amp; Technology - Other Topics, General &amp; Internal Medicine, Pharmacology &amp; Pharmacy).<br><br>CONCLUSION: The introduced TMSD, which incorporates the FLCA algorithm and features in 3 columns-cited, active, and citing research categories-offers readers clearer insights into research developments compared to the traditional dual-map overlays from CiteSpace software. Such tools are especially valuable for streamlining the visualization of the intricate data often seen in bibliometric studies.},
}
@article {pmid38239942,
year = {2024},
author = {Dastaviz, F and Vahidi, A and Khosravi, T and Khosravi, A and Sheikh Arabi, M and Bagheri, A and Rashidi, M and Oladnabi, M},
title = {Impact of umbelliprenin-containing niosome nanoparticles on VEGF-A and CTGF genes expression in retinal pigment epithelium cells.},
journal = {International journal of ophthalmology},
volume = {17},
number = {1},
pages = {7-15},
pmid = {38239942},
issn = {2222-3959},
abstract = {AIM: To investigate the impact of niosome nanoparticles carrying umbelliprenin (UMB), an anti-angiogenic and anti-inflammatory plant compound, on the expression of vascular endothelial growth factor (VEGF-A) and connective tissue growth factor (CTGF) genes in a human retinal pigment epithelium (RPE)-like retina-derived cell line.<br><br>METHODS: UMB-containing niosomes were created, optimized, and characterized. RPE-like cells were treated with free UMB and UMB-containing niosomes. The IC50 values of the treatments were determined using an MTT assay. Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis. Niosomes' characteristics, including drug entrapment efficiency, size, dispersion index, and zeta potential were assessed. Free UMB had an IC50 of 96.2 &#xb5;g/mL, while UMB-containing niosomes had an IC50 of 25 &#xb5;g/mL.<br><br>RESULTS: Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells (P=0.001). Additionally, UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells (P=0.05). However, there was no significant reduction in the expression of both genes in cells treated with free UMB.<br><br>CONCLUSION: Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression. However, the latter demonstrates significantly greater efficacy, potentially due to the lower UMB dosage and gradual delivery. These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.},
}
@article {pmid38239939,
year = {2024},
author = {Tang, QQ and Yang, XG and Wang, HQ and Wu, DW and Zhang, MX},
title = {Applications of deep learning for detecting ophthalmic diseases with ultrawide-field fundus images.},
journal = {International journal of ophthalmology},
volume = {17},
number = {1},
pages = {188-200},
pmid = {38239939},
issn = {2222-3959},
abstract = {AIM: To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages, limitations, and possible solutions common to all tasks.<br><br>METHODS: We searched three academic databases, including PubMed, Web of Science, and Ovid, with the date of August 2022. We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords, of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images.<br><br>RESULTS: Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance, including diabetic retinopathy, glaucoma, age-related macular degeneration, retinal vein occlusions, retinal detachment, and other peripheral retinal diseases. Compared to fundus images, the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200&#xb0; in a single exposure, which can observe more areas of the retina.<br><br>CONCLUSION: The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future.},
}
@article {pmid38239611,
year = {2023},
author = {Gao, Y and Zhang, S and Zhao, Y and Yang, T and Moreira, P and Sun, G},
title = {Reduction of retinal vessel density in non-exudative macular neovascularization: a retrospective study.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1219423},
pmid = {38239611},
issn = {2296-858X},
abstract = {PURPOSE: The purpose of this study is to identify predictive activation biomarkers in retinal microvascular characteristics of non-exudative macular neovascularization (MNV) and avoid delayed treatment or overtreatment of subclinical MNV. The main objective is to contribute to the international debate on a new understanding of the role of retinal vessel features in the pathogenesis and progression of non-exudative MNV and age-related macular degeneration (AMD). A discussion on revising-related clinical protocols is presented.<br><br>METHODS: In this retrospective study, the authors included eyes with non-exudative MNV, eyes with exudative AMD, and normal eyes of age-matched healthy subjects. The parameters were obtained by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA).<br><br>RESULTS: In total, 21 eyes with exudative AMD, 21 eyes with non-exudative MNV, and 20 eyes of 20 age-matched healthy subjects without retinal pathology were included. Vessel density (VD) of the deep vascular complex (DVC) in eyes with non-exudative MNV was significantly greater than that in eyes with exudative AMD (p&#x2009;=&#x2009;0.002), while for superficial vascular plexus (SVP) metrics, no VD differences among sectors were observed between eyes with non-exudative MNV and eyes with exudative AMD.<br><br>CONCLUSION: The reduction in retinal vessel density, especially in the DVC, seems to be involved in or be accompanied by non-exudative MNV activation and should be closely monitored during follow-up visits in order to ensure prompt anti-angiogenic therapy. A discussion on applicable clinical protocols is presented aiming to contribute to new insights into ophthalmology service development which is directed to this specific type of patient and diagnosis.},
}
@article {pmid38239418,
year = {2023},
author = {Ahmed, HS and Thrishulamurthy, CJ},
title = {Advancing Diabetic Retinopathy Diagnosis: Leveraging Optical Coherence Tomography Imaging with Convolutional Neural Networks.},
journal = {Romanian journal of ophthalmology},
volume = {67},
number = {4},
pages = {398-402},
pmid = {38239418},
issn = {2501-2533},
mesh = {Humans ; *Diabetic Retinopathy/diagnosis/complications ; Tomography, Optical Coherence/methods ; *Macular Edema/etiology ; Vascular Endothelial Growth Factor A ; Artificial Intelligence ; Neural Networks, Computer ; *Macular Degeneration ; *Diabetes Mellitus ; },
abstract = {Diabetic retinopathy (DR) is a vision-threatening complication of diabetes, necessitating early and accurate diagnosis. The combination of optical coherence tomography (OCT) imaging with convolutional neural networks (CNNs) has emerged as a promising approach for enhancing DR diagnosis. OCT provides detailed retinal morphology information, while CNNs analyze OCT images for automated detection and classification of DR. This paper reviews the current research on OCT imaging and CNNs for DR diagnosis, discussing their technical aspects and suitability. It explores CNN applications in detecting lesions, segmenting microaneurysms, and assessing disease severity, showing high sensitivity and accuracy. CNN models outperform traditional methods and rival expert ophthalmologists' results. However, challenges such as dataset availability and model interpretability remain. Future directions include multimodal imaging integration and real-time, point-of-care CNN systems for DR screening. The integration of OCT imaging with CNNs has transformative potential in DR diagnosis, facilitating early intervention, personalized treatments, and improved patient outcomes. Abbreviations: DR = Diabetic Retinopathy, OCT = Optical Coherence Tomography, CNN = Convolutional Neural Network, CMV = Cytomegalovirus, PDR = Proliferative Diabetic Retinopathy, AMD = Age-Related Macular Degeneration, VEGF = vascular endothelial growth factor, RAP = Retinal Angiomatous Proliferation, OCTA = OCT Angiography, AI = Artificial Intelligence.},
}
@article {pmid38238339,
year = {2024},
author = {Lapaquette, P and Terrat, S and Proukhnitzky, L and Martine, L and Grégoire, S and Buteau, B and Cabaret, S and Rieu, A and Bermúdez-Humarán, LG and Gabrielle, PH and Creuzot-Garcher, C and Berdeaux, O and Acar, N and Bringer, MA},
title = {Long-term intake of Lactobacillus helveticus enhances bioavailability of omega-3 fatty acids in the mouse retina.},
journal = {NPJ biofilms and microbiomes},
volume = {10},
number = {1},
pages = {4},
pmid = {38238339},
issn = {2055-5008},
support = {ANR-11-LABX-0021-01//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-15-IDEX-0003//Agence Nationale de la Recherche (French National Research Agency)/ ; },
mesh = {Animals ; Mice ; *Fatty Acids, Omega-3/analysis/metabolism ; *Lactobacillus helveticus/metabolism ; Biological Availability ; Diet ; Retina/chemistry/metabolism ; },
abstract = {Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several observational studies indicate that consumption of a diet with relatively high levels of n-3 PUFAs, such as those provided by fish oils, has a protective effect against the development of age-related macular degeneration. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lactobacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.},
}
@article {pmid38238063,
year = {2024},
author = {Dinah, C and Enoch, J and Ghulakhszian, A and Sekhon, M and Crabb, DP and Taylor, DJ},
title = {Patient acceptability of intravitreal complement inhibitors in geographic atrophy (GA): protocol for a UK-based cross-sectional study.},
journal = {BMJ open},
volume = {14},
number = {1},
pages = {e075713},
pmid = {38238063},
issn = {2044-6055},
mesh = {Humans ; *Geographic Atrophy/drug therapy ; Cross-Sectional Studies ; Complement Inactivating Agents/therapeutic use ; State Medicine ; *Macular Degeneration/drug therapy ; United Kingdom ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy ; },
abstract = {INTRODUCTION: Geographic atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD). Previously untreatable, complement inhibitors delivered by regular intravitreal injections have recently been demonstrated to slow down the progression of GA lesions in phase 3 trials. One such treatment, Syfovre (pegcetacoplan), was approved by the US Food and Drug Administration in February 2023. These therapies slow down, but do not stop or reverse, the progression of GA; they may also increase the risk of developing the neovascular ('wet') type of AMD. In light of these developments, this study aims to quantify the acceptability of these new intravitreal injection treatments to patients with GA in the UK and explore factors that may influence the acceptability of these treatments.<br><br>METHODS AND ANALYSIS: In this cross-sectional, non-interventional study, the primary objective is to determine the proportion of patients with GA that find regular intravitreal therapy acceptable for slowing the progression of GA. We will use a validated acceptability questionnaire in order to quantify the acceptability of new treatments among patients with GA. The correlation between acceptability and functional and structural biomarkers of GA will be established. We will also explore demographic, general health and ocular factors that may influence acceptability. 180 individuals with a diagnosis of GA will be recruited from 7 to 8 participating National Health Service trusts across the UK. Multiple regression analysis will be conducted to determine the simultaneous effects of multiple factors on patient acceptability.<br><br>ETHICS AND DISSEMINATION: The study received ethical approval from the Health Research Authority on 14 March 2023 (IRAS Project ID: 324854). Findings will be disseminated through peer-reviewed publications and conference presentations to the medical retina community, as well as through dialogue with patients and macular disease charities.},
}
@article {pmid38236924,
year = {2024},
author = {Kyei, S and Kwasi Gyaami, R and Abowine, JB and Zaabaar, E and Asiedu, K and Boadi-Kusi, SB and Mesuh, JM and Assiamah, F and Armah, A and Ayerakwah, PA},
title = {Risk of major myopia-associated non-communicable ocular health disorders in Ghana.},
journal = {PloS one},
volume = {19},
number = {1},
pages = {e0297052},
pmid = {38236924},
issn = {1932-6203},
mesh = {Adult ; Retrospective Studies ; *Macular Degeneration ; *Glaucoma, Open-Angle ; Child ; Conjunctiva/abnormalities ; Child, Preschool ; Ghana/epidemiology ; Female ; *Cataract/epidemiology ; Humans ; *Pterygium ; Refraction, Ocular ; Middle Aged ; Male ; Young Adult ; Aged, 80 and over ; Adolescent ; *Myopia/epidemiology/diagnosis ; Aged ; },
abstract = {OBJECTIVE: To assess the differential association of myopia with major non-communicable ocular diseases in an African clinical cohort.<br><br>METHODS: A five-year hospital-based retrospective study of myopia cases. Patients' folders, Optical Coherence Tomography scans, and fundus photographs were reviewed for the abstraction of relevant data. Only records that employed recognized standards and classification systems for diagnosing and staging the various ocular conditions were included. Demographic characteristics, non-cycloplegic objective refractive findings, and non-communicable eye diseases were retrieved from the records. Myopia-associated risk factors were then determined using logistic regression and correlation.<br><br>RESULTS: Some 16018 patients (32027 eyes) met the inclusion criteria for at least one eye comprising 50.8% males (n = 8137) and 49.2% females (n = 7881). The mean age of the patients was 43.14 &#xb1; 17.88 years (range: 2-98 years). The mean spherical equivalent&#xb1; Standard deviation for myopia was -2.30&#xb1;3.23 DS (range: -0.50 to -25DS). Binary logistic regression analysis showed that myopic eyes had a higher odd of AC (OR, 0.53; 95% CI, 0.50-0.57), POAG (OR, 6.0; 95% CI, 5.26-6.82), DR (OR, 10.70; 95% CI, 3.91-29.27) and cataracts (OR, 20; 95% CI, 15.32-26.20) but not dry eye (OR, 0.74, 95% CI, 0.68-0.81), macular degeneration and pterygium (OR, 0.36; 95% CI, 0.32-0.40).<br><br>CONCLUSION: Africans with myopia are more at risk of developing allergic conjunctivitis, cataracts, POAG, and DR but not for dry eye, macular degeneration, and pterygium.},
}
@article {pmid38236187,
year = {2024},
author = {Greig, EC and Moult, EM and Despotovic, IN and Hodgson, LAB and Pramil, V and Fujimoto, JG and Waheed, NK and Guymer, RH and Wu, Z},
title = {Assessment of Choriocapillaris Flow Prior to Nascent Geographic Atrophy Development Using Optical Coherence Tomography Angiography.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {1},
pages = {33},
pmid = {38236187},
issn = {1552-5783},
support = {R01 EY011289/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Tomography, Optical Coherence ; *Geographic Atrophy/diagnosis ; Prospective Studies ; Choroid ; *Macular Degeneration/diagnosis ; Angiography ; },
abstract = {PURPOSE: To assess the relationship between choriocapillaris (CC) loss and the development of nascent geographic atrophy (nGA) using optical coherence tomography angiography (OCTA) imaging.<br><br>METHODS: In total, 105 from 62 participants with bilateral large drusen, without late age-related macular degeneration (AMD) or nGA at baseline, were included in this prospective, longitudinal, observational study. Participants underwent swept-source OCTA imaging at 6-month intervals. CC flow deficit percentage (FD%) and drusen volume measurements were determined for the visit prior to nGA development or the second-to-last visit if nGA did not develop. Global and local analyses, the latter based on analyses within superpixels (120 &#xd7; 120-&#xb5;m regions), were performed to examine the association between CC FD% and future nGA development.<br><br>RESULTS: A total of 15 (14%) eyes from 12 (19%) participants developed nGA. There was no significant difference in global CC FD% at the visit prior to nGA development between eyes that developed nGA and those that did not (P&#xa0;=&#xa0;0.399). In contrast, CC FD% was significantly higher in superpixels that subsequently developed nGA compared to those that did not (P&#xa0;<&#xa0;0.001), and a model utilizing CC FD% was significantly better at predicting foci of future nGA development at the superpixel level than a model using drusen volume alone (P&#xa0;&#x2264;&#xa0;0.040).<br><br>CONCLUSIONS: This study showed that significant impairments in CC blood flow could be detected locally prior to the development of nGA. These findings add to our understanding of the pathophysiologic changes that occur with atrophy development in AMD.},
}
@article {pmid38235630,
year = {2023},
author = {Fursova, AZ and Nikulich, IF and Dmitrieva, EI and Gusarevich, OG and Derbeneva, AS and Vasilyeva, MA and Kozhevnikova, OS and Kolosova, NG and Rabota, FK},
title = {[Prognosis criteria of optical coherence tomography angiography for the long-term efficacy of anti-VEGF therapy of neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {6},
pages = {50-58},
doi = {10.17116/oftalma202313906150},
pmid = {38235630},
issn = {0042-465X},
mesh = {Humans ; Aged ; Aged, 80 and over ; Ranibizumab/therapeutic use ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/therapeutic use ; Prognosis ; Neovascularization, Pathologic/drug therapy ; Retina ; Intravitreal Injections ; *Macular Degeneration/diagnostic imaging/drug therapy ; Angiography ; Fluorescein Angiography ; *Wet Macular Degeneration/complications/drug therapy ; Retrospective Studies ; },
abstract = {PURPOSE: The study aimed to determine the most significant optical coherence tomography angiography (OCTA) parameters in terms of predicting anti-VEGF therapy effectiveness during long-term (3-year) follow-up of patients with neovascular age-related macular degeneration (nAMD).<br><br>MATERIAL AND METHODS: The study included 122 patients (122 eyes) with mean age of 73.4&#xb1;6.6 years who were diagnosed with nAMD. Subgroup analysis included 50 patients (50 eyes) with detailed OCT angiography examination of macular neovascularization (MNV) characteristics and their changes in the course of the follow-up, which lasted 144 weeks. All patients were treated by angiogenesis inhibitor (aflibercept 2 mg), most of them - according to Treat-and-Extend protocol.<br><br>RESULTS: Treatment response (either 'good' or 'partial') was achieved in all patients, and the proportion of the response types was similar in both types 1 and 2 MNV. Key OCTA parameters associated with the number of injections, as well as morphological and functional response (best-corrected visual acuity, retinal neuroepithelium and pigment epithelium detachment), were vascular network area and MNV area assessed at baseline and three months after treatment initiation. Both of these parameters were closely related in both MNV types during the follow-up. Key parameter with maximum number of clinically significant correlations ('very high' strength, p<0.05) in eyes with 'good' response was MNV area, in eyes with 'partial' response - vascular density and greatest vascular caliber.<br><br>CONCLUSIONS: Vascular network area and MNV area assessed at baseline and after three loading doses were determined as the most significant OCTA characteristics for predicting the number of injections and treatment response based on functional and morphological parameters. MNV area was found to be the most clinically significant marker in 'good' response, vascular density and greatest vascular caliber - in 'partial' response.},
}
@article {pmid38235629,
year = {2023},
author = {Gar'kavenko, VV and Salmin, VV and Balashova, PM and Gaydelis, VS and Kokozova, DS},
title = {[Spectrofluorimetric changes in the lens after intravitreal injections of brolucizumab].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {6},
pages = {41-49},
doi = {10.17116/oftalma202313906141},
pmid = {38235629},
issn = {0042-465X},
mesh = {Humans ; Adult ; Intravitreal Injections ; Angiogenesis Inhibitors/adverse effects ; Vascular Endothelial Growth Factor A ; Prospective Studies ; Spectrometry, Fluorescence ; *Cataract/chemically induced/diagnosis ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy ; Retrospective Studies ; *Antibodies, Monoclonal, Humanized ; },
abstract = {UNLABELLED: Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are actively used in the treatment of various ophthalmic pathologies. In addition to the pronounced therapeutic effect of anti-VEGF drugs described in the literature, a number of data on adverse effects associated with the use of IVI, including from the lens, have now been accumulated. Prevention of possible side effects of this type of treatment requires further investigation.<br><br>PURPOSE: The study evaluates the changes in spectrofluorometric parameters of the lens after intravitreal injections of brolucizumab in eyes with native lens.<br><br>MATERIAL AND METHODS: The study included 13 people with neovascular age-related macular degeneration (AMD) who received IVI of brolucizumab. All patients were over 40 years old; changes in central retinal thickness in the macular area exceeded 300 &#x3bc;m according to optical coherence tomography. Spectrofluorimetric indicators of the lens were studied before and after injections of the drug in both eyes. The spectra were analyzed in the wavelength range 412-698 nm to record the changes in the content of non-tryptophan fluorophore molecules in the lens.<br><br>RESULTS: Spectrofluorimetry revealed metabolic changes in the native lens after intravitreal injections of the drug brolucizumab. No such changes were observed in the lens of the eyes not injected with the drug (the &#xab;Control&#xbb; group). The proposed investigation technique involves prospective assessment of the safety of various molecules injected intravitreally in terms of cataract development at various times after the injection.<br><br>CONCLUSION: Spectrofluorimetry can be used for identifying initial metabolic changes in the lens. It is a promising method for assessing the molecules used in intravitreal injections in terms of their safety for the native lens, as well as for development of detailed instructions for clinically substantiated use of drugs with adverse effects in the form of cataract induction. According to spectrofluorimetry, IVI of the drug brolucizumab affects metabolic changes in the lens.},
}
@article {pmid38235627,
year = {2023},
author = {Neroev, VV and Chesnokova, NB and Neroeva, NV and Beznos, OV and Pavlenko, TA and Okhotsimskaya, TD and Utkina, OA},
title = {[Pathogenetic role of multifunctional protein alpha-2-macroglobulin and its activity in tears and serum in age-related macular degeneration and proliferative diabetic retinopathy].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {6},
pages = {26-32},
doi = {10.17116/oftalma202313906126},
pmid = {38235627},
issn = {0042-465X},
mesh = {Humans ; *Diabetes Mellitus ; *Diabetic Retinopathy/diagnosis/etiology/metabolism ; Inflammation ; Macroglobulins ; *Macular Degeneration/diagnosis/etiology ; Retina ; Serum/metabolism ; },
abstract = {UNLABELLED: Alpha-2-macroglobulin (α2-MG) is a multifunctional protein involved in neurodegeneration, inflammation and neovascularization, which are key processes in the pathogenesis of age-related macular degeneration (AMD) and proliferative diabetic retinopathy (PDR). AMD and PDR are two of the main causes of vision loss and blindness, are difficult to treat, and are generally diagnosed at the stage of irreversible changes.<br><br>PURPOSE: This study estimates the activity of &#x3b1;2-MG in the blood serum and tears of patients with AMD and PDR in order to reveal the relation of its levels with the intensity of the pathological process in the retina.<br><br>MATERIAL AND METHODS: The study included 17 patients (34 eyes) with AMD, 15 patients (30 eyes) with PDR, and 15 healthy adults (30 eyes) of the similar age. The activity of &#x3b1;2-MG in serum and tears was measured enzymatically using the specific substrate N-benzoyl-DL-arginine-p-nitroanilide (BAPNA).<br><br>RESULTS: The activity of &#x3b1;2-MG in tears of patients with AMD was on the average 3.5 times higher than in healthy controls, and in patients with PDR - 1.5 times higher. Patients with AMD at the submacular fibrosis stage showed decreased &#x3b1;2-MG activity in tears. The activity of &#x3b1;2-MG in serum of patients with AMD and PDR was on the average 25% higher than in healthy persons. No correlation was revealed between serum and tear levels of &#x3b1;2-MG activity.<br><br>CONCLUSION: This study revealed for the first time that in AMD and PDR the activity of &#x3b1;2-MG in tears is increased, and that in AMD the increase is higher than in PDR. An increase of &#x3b1;2-MG activity in serum confirms the presence of systemic inflammation. Absence of correlation between the serum and tear activity of &#x3b1;2-MG confirms its local origin. The high level of &#x3b1;2-MG activity in tears reflects the presence of an active destructive process in the retina, justifying its further investigation as a predictor of AMD and PDR course, as well as an indicator of therapy effectiveness.},
}
@article {pmid38234525,
year = {2024},
author = {Longevity, OMAC},
title = {Retracted: Sirtuin 1 Induces Choroidal Neovascularization and Triggers Age-Related Macular Degeneration by Promoting LCN2 through SOX9 Deacetylation.},
journal = {Oxidative medicine and cellular longevity},
volume = {2024},
number = {},
pages = {9842919},
pmid = {38234525},
issn = {1942-0994},
abstract = {[This retracts the article DOI: 10.1155/2022/1671438.].},
}
@article {pmid38233896,
year = {2024},
author = {Penha, FM and Masud, M and Khanani, ZA and Thomas, M and Fong, RD and Smith, K and Chand, A and Khan, M and Gahn, G and Melo, GB and Khanani, AM},
title = {Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME.},
journal = {International journal of retina and vitreous},
volume = {10},
number = {1},
pages = {5},
pmid = {38233896},
issn = {2056-9920},
support = {F. Hoffmann-La Roche//F. Hoffmann-La Roche/ ; },
abstract = {Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.},
}
@article {pmid38233865,
year = {2024},
author = {Roubeix, C and Nous, C and Augustin, S and Ronning, KE and Mathis, T and Blond, F and Lagouge-Roussey, P and Crespo-Garcia, S and Sullivan, PM and Gautier, EL and Reichhart, N and Sahel, JA and Burns, ME and Paques, M and Sørensen, TL and Strauss, O and Guillonneau, X and Delarasse, C and Sennlaub, F},
title = {Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration.},
journal = {Journal of neuroinflammation},
volume = {21},
number = {1},
pages = {22},
pmid = {38233865},
issn = {1742-2094},
support = {ANR-15-CE14-0015-01//Agence Nationale de la Recherche/ ; ANR-10-LABX-65//Agence Nationale de la Recherche/ ; ANR-10-LABX-65//Agence Nationale de la Recherche/ ; ANR-18-IAHU-0001//Agence Nationale de la Recherche/ ; ANR-15-CE14-0015-01//Agence Nationale de la Recherche/ ; },
mesh = {Humans ; Mice ; Animals ; Aged ; Monocytes/pathology ; Angiotensin II ; *Macular Degeneration/genetics ; Inflammation/genetics ; *Choroidal Neovascularization ; },
abstract = {Age-related macular degeneration (AMD) is invariably associated with the chronic accumulation of activated mononuclear phagocytes in the subretinal space. The mononuclear phagocytes are composed of microglial cells but also of monocyte-derived cells, which promote photoreceptor degeneration and choroidal neovascularization. Infiltrating blood monocytes can originate directly from bone marrow, but also from a splenic reservoir, where bone marrow monocytes develop into angiotensin II receptor (ATR1)[+] splenic monocytes. The involvement of splenic monocytes in neurodegenerative diseases such as AMD is not well understood. Using acute inflammatory and well-phenotyped AMD models, we demonstrate that angiotensin II mobilizes ATR1[+] splenic monocytes, which we show are defined by a transcriptional signature using single-cell RNA sequencing and differ functionally from bone marrow monocytes. Splenic monocytes participate in the chorio-retinal infiltration and their inhibition by ATR1 antagonist and splenectomy reduces the subretinal mononuclear phagocyte accumulation and pathological choroidal neovascularization formation. In aged AMD-risk ApoE2-expressing mice, a chronic AMD model, ATR1 antagonist and splenectomy also inhibit the chronic retinal inflammation and associated cone degeneration that characterizes these mice. Our observation of elevated levels of plasma angiotensin II in AMD patients, suggests that similar events take place in clinical disease and argue for the therapeutic potential of ATR1 antagonists to inhibit splenic monocytes for the treatment of blinding AMD.},
}
@article {pmid38232696,
year = {2024},
author = {Lin, JB and Santeford, A and Colasanti, JJ and Lee, Y and Shah, AV and Wang, TJ and Ruzycki, PA and Apte, RS},
title = {Targeting cell-type-specific, choroid-peripheral immune signaling to treat age-related macular degeneration.},
journal = {Cell reports. Medicine},
volume = {5},
number = {1},
pages = {101353},
pmid = {38232696},
issn = {2666-3791},
support = {P30 EY002687/EY/NEI NIH HHS/United States ; R01 EY019287/EY/NEI NIH HHS/United States ; F30 DK130282/DK/NIDDK NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Mice ; Animals ; *Choroidal Neovascularization/genetics/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism ; Leukocytes, Mononuclear/metabolism ; Endothelial Cells/metabolism ; *Macular Degeneration/genetics/complications/metabolism ; Choroid/metabolism/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness featuring pathogenic neovascularization of the choroidal vasculature (CNV). Although systemic immunity plays a role in AMD, the ocular signals that recruit and activate immune cells remain poorly defined. Using single-cell RNA sequencing, we prospectively profile peripheral blood mononuclear cells from 65 individuals including AMD and controls, which we integrate with existing choroid data. We generate a network of choroid-peripheral immune interactions dysregulated in AMD, including known AMD-relevant gene vascular endothelial growth factor (VEGF) receptor 2. Additionally, we find CYR61 is upregulated in choroidal veins and may signal to circulating monocytes. In mice, we validate that CYR61 is abundant in endothelial cells within CNV lesions neighboring monocyte-derived macrophages. Mechanistically, CYR61 activates macrophage anti-angiogenic gene expression, and ocular Cyr61 knockdown increases murine CNV size, indicating CYR61 inhibits CNV. This study highlights the potential of multi-tissue human datasets to identify disease-relevant and potentially therapeutically modifiable targets.},
}
@article {pmid38231804,
year = {2024},
author = {Elsharkawy, M and Sharafeldeen, A and Khalifa, F and Soliman, A and Elnakib, A and Ghazal, M and Sewelam, A and Thanos, A and Sandhu, HS and El-Baz, A},
title = {A Clinically Explainable AI-Based Grading System for Age-Related Macular Degeneration Using Optical Coherence Tomography.},
journal = {IEEE journal of biomedical and health informatics},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/JBHI.2024.3355329},
pmid = {38231804},
issn = {2168-2208},
abstract = {We propose an automated, explainable artificial intelligence (xAI) system for age-related macular degeneration (AMD) diagnosis. Mimicking the physician's perceptions, the proposed xAI system is capable of deriving clinically meaningful features from optical coherence tomography (OCT) B-scan images to differentiate between a normal retina, different grades of AMD (early, intermediate, geographic atrophy (GA), inactive wet or active neovascular disease [exudative or wet AMD]), and non-AMD diseases. Particularly, we extract retinal OCT-based clinical imaging markers that are correlated with the progression of AMD, which include: (i) subretinal tissue, sub-retinal pigment epithelial tissue, intraretinal fluid, subretinal fluid, and choroidal hypertransmission detection using a DeepLabV3+ network; (ii) detection of merged retina layers using a novel convolutional neural network model; (iii) drusen detection based on 2D curvature analysis; (iv) estimation of retinal layers' thickness, and first-order and higher-order reflectivity features. Those clinical features are used to grade a retinal OCT in a hierarchical decision tree process. The first step looks for severe disruption of retinal layers' indicative of advanced AMD. These cases are analyzed further to diagnose GA, inactive wet AMD, active wet AMD, and non-AMD diseases. Less severe cases are analyzed using a different pipeline to identify OCT with AMD-specific pathology, which is graded as intermediate-stage or early-stage AMD. The remainder is classified as either being a normal retina or having other non-AMD pathology. The proposed system in the multi-way classification task, evaluated on 1285 OCT images, achieved 90.82% accuracy. These promising results demonstrated the capability to automatically distinguish between normal eyes and all AMD grades in addition to non-AMD diseases.},
}
@article {pmid38228633,
year = {2024},
author = {Pastore, MR and Milan, S and Cirigliano, G and Tognetto, D},
title = {Functional and anatomical outcomes of brolucizumab for nAMD in a real-life setting.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {1441},
pmid = {38228633},
issn = {2045-2322},
mesh = {Humans ; Angiogenesis Inhibitors ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Visual Acuity ; Intravitreal Injections ; *Retinal Detachment/drug therapy ; *Wet Macular Degeneration/drug therapy ; *Antibodies, Monoclonal, Humanized ; },
abstract = {To report long-term outcomes of brolucizumab in neovascular age-related macular degeneration (nAMD) treatment. Records from 74 patients were retrospectively reviewed. Both naïve eyes and those previously treated with other antiVEGF agents were included. Primary outcomes included variation in best corrected visual acuity (BCVA), central subfield thickness (CST), intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) dimensions. Outcomes were reviewed after the loading phase, at week 24, and at last follow-up. IOI occurrence represented the secondary outcome. BCVA improved significantly in both groups. In switched eyes, IRF and SRF were significantly reduced at every timepoint, with CST reduction from week 24 (p = 0.005). In naïve group, CST decreased from the loading phase (p = 0.006) and all patients showed dry macula from week 24. A significant reduction in PED maximum high was demonstrated in both groups. In seven naïve eyes, PED completely reabsorbed; a slight increase in PED horizontal maximal diameter was also observed from week 24. IOI occurred in 5.4% of cases. In conclusion, brolucizumab showed a strong drying effect, permitting functional improvement together with fluid reabsorption and an encouraging modification of PED dimension, especially on naïve patients. These results together with the extension of treatment intervals make brolucizumab an efficient therapeutic strategy for nAMD.},
}
@article {pmid38227312,
year = {2024},
author = {Kim, SH and Kim, YK and Shin, YI and Kang, G and Kim, SP and Lee, H and Hong, IH and Chang, IB and Hong, SB and Yoon, HJ and Ha, A},
title = {Nighttime Outdoor Artificial Light and Risk of Age-Related Macular Degeneration.},
journal = {JAMA network open},
volume = {7},
number = {1},
pages = {e2351650},
pmid = {38227312},
issn = {2574-3805},
mesh = {Aged ; Humans ; Male ; Case-Control Studies ; Databases, Factual ; *Macular Degeneration/epidemiology/etiology ; Republic of Korea ; *Lighting/adverse effects ; },
abstract = {IMPORTANCE: Light pollution's impact on human health is increasingly recognized, but its link to exudative age-related macular degeneration (EAMD) remains unclear.<br><br>OBJECTIVE: To investigate the association between exposure to outdoor artificial light at night (OALAN) and the risk of incident EAMD.<br><br>In this nationwide population-based case-control study, all individuals 50 years or older with newly diagnosed EAMD between January 1, 2010, and December 31, 2011, were identified with reference to the Korean National Health Insurance Service registration program database for rare and intractable diseases. Birth year- and sex-matched controls (with no EAMD diagnosis until 2020) were selected at a 1:30 ratio. Data were acquired from May 1 to December 31, 2021, and analyzed from June 1 to November 30, 2022.<br><br>EXPOSURES: Mean levels of OALAN at participants' residential addresses during 2008 and 2009 were estimated using time-varying satellite data for a composite view of persistent nighttime illumination at&#x2009;an approximate scale of&#x2009;1 km2.<br><br>MAIN OUTCOMES AND MEASURES: The hazard ratios (HRs) and 95% CIs of the association between residential OALAN and risk of incident EAMD were determined based on maximum likelihood estimation after adjusting for sociodemographic characteristics, comorbidities, and area-level risk factors (ie, nighttime traffic noise and particulate matter of aerodynamic diameter &#x2264;10 &#x3bc;m in each participant's administrative district of residence).<br><br>RESULTS: A total of 126 418 participants were included in the analysis (mean [SD] age, 66.0 [7.9] years; 78 244 men [61.9%]). Of these, 4078 were patients with newly diagnosed EAMD and 122&#x202f;340 were EAMD-free matched controls. In fully adjusted models, an IQR (55.8 nW/cm2/sr) increase in OALAN level was associated with an HR of 1.67 (95% CI, 1.56-1.78) for incident EAMD. The exposure-response curve demonstrated a nonlinear, concave upward slope becoming more pronounced at higher levels of light exposure (ie, at&#x2009;approximately&#x2009;110 nW/cm2/sr). In a subgroup analysis, an IQR increase in OALAN was associated with increased risk of incident EAMD in urban areas (HR, 1.46 [95% CI, 1.33-1.61]) but not in rural areas (HR, 1.01 [95% CI, 0.84-1.22]).<br><br>CONCLUSIONS AND RELEVANCE: In this nationwide population-based case-control study, higher levels of residential OALAN were associated with an increased risk of incident EAMD. Future studies with more detailed information on exposure, individual adaptive behaviors, and potential mediators are warranted.},
}
@article {pmid38225654,
year = {2024},
author = {Fitzpatrick, NK and Chachay, V and Capra, S and Briskey, D and Jackman, S and Shore, A and Bowtell, J},
title = {Assessing electronic device use behaviours in healthy adults: development and evaluation of a novel tool.},
journal = {BMC public health},
volume = {24},
number = {1},
pages = {186},
pmid = {38225654},
issn = {1471-2458},
mesh = {Adult ; Humans ; Australia ; Surveys and Questionnaires ; *Mental Recall ; *Television ; United Kingdom ; Reproducibility of Results ; },
abstract = {BACKGROUND: Chronic exposure of the macula to blue light from electronic devices has been identified as a potential macular health concern. The impacts remain poorly investigated as no validated methods to capture usual device use behaviours exist.<br><br>PURPOSE: The aim of this study was to develop and validate the Electronic Device Use Questionnaire (EDUQ) against multiple 24-h electronic&#xa0;device use diaries in healthy Australian and United Kingdom adults.<br><br>METHODS: The EDUQ and diaries were developed to capture device use across categories (television, computer and handheld devices). Over eight weeks 56 Australian and 24 United Kingdom participants completed three questionnaires and eight diaries via online platforms. Tool validity was determined through Bland-Altman plot analysis of mean daily hours of device use between the tools.<br><br>RESULTS: The EDUQ demonstrated poor validity in both cohorts with poor agreement when compared with the diaries. When the device categories were combined, a mean difference between the tools of 1.54&#xa0;h/day, and 95% limits of agreement between -2.72&#xa0;h/day and 5.80&#xa0;h/day was observed in the Australian cohort. Across both cohorts and all device categories the mean differences indicated individuals were more likely to report higher device use through the questionnaire rather than diaries.<br><br>CONCLUSIONS: The EDUQ is a novel tool and demonstrated the difficulty for participants of accurately recalling usual behaviour of device use. Poor agreement in reported device use occurred across all device categories. The poor agreement may be related to factors such as memory recall bias, and the number of diaries captured not being reflective of usual use. Future studies should look to address these factors to improve validity of device use capture.},
}
@article {pmid38224636,
year = {2024},
author = {Xiu, X and Li, M and Hu, D and Jia, H and Wang, H and Liu, Y and Zhao, X and Li, Z and Liu, Y and Yang, H and Cheng, M},
title = {Potential oral VEGFR2 inhibitors: Treatment of wet age-related macular degeneration.},
journal = {Bioorganic chemistry},
volume = {144},
number = {},
pages = {107110},
doi = {10.1016/j.bioorg.2024.107110},
pmid = {38224636},
issn = {1090-2120},
mesh = {Mice ; Animals ; Humans ; Mice, Inbred ICR ; Human Umbilical Vein Endothelial Cells ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/pharmacology ; Vascular Endothelial Growth Factor Receptor-2 ; },
abstract = {Wet age-related macular degeneration (w-AMD) is one of the leading causes of vision loss in industrialized countries. A large body of evidence suggests that inhibitors targeting VEGFR2 may be effective in the treatment of w-AMD. The identification of an oral VEGFR2 inhibitor for the treatment of w-AMD provides an opportunity for a route of administration other than intravitreal injection. While screening potent VEGFR2 inhibitors at the enzyme and cellular levels, ensuring the safety of the compounds was our primary strategy for screening optimal compounds. Finally, compound 16 was identified, exhibiting enhanced inhibition of VEGFR2 enzyme and proliferation of BaF3-TEL-VEGFR2 cells compared to Vorolanib. Compound 16 had a weak inhibitory effect on human Ether-a-go-go-related gene (hERG) channel currents, showing a cardiac safety profile similar to Vorolanib. Compound 16 showed no significant toxicity to human liver cell LX-2, indicating a liver safety profile similar to Vorolanib. The water solubility of compound 16 was found to be higher than that of Vorolanib when tested at pH = 7.4. In addition, compound 16 was found to inhibit VEGFR2 phosphorylation in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner by WB assay. Furthermore, the in vitro preliminary evaluation of the drug-like properties of compound 16 showed remarkable plasma stability and moderate liver microsomal stability. Based on in vivo pharmacokinetic studies in ICR mice, compound 16 exhibited acceptable oral bioavailability (F = 20.2 %). Overall, these findings provide evidence that compound 16 is a leading potential oral drug candidate for w-AMD.},
}
@article {pmid38223782,
year = {2024},
author = {Witkin, AJ and Jaffe, GJ and Srivastava, SK and Davis, JL and Kim, JE},
title = {Retinal Vasculitis After Intravitreal Pegcetacoplan: Report From the ASRS Research and Safety in Therapeutics (ReST) Committee.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {1},
pages = {9-20},
pmid = {38223782},
issn = {2474-1272},
abstract = {Purpose: To analyze post-marketing cases of retinal vasculitis after intravitreal pegcetacoplan. Methods: The American Society of Retina Specialists (ASRS) Research and Safety in Therapeutics (ReST) Committee as well as an expert panel performed a retrospective review of cases of retinal vasculitis reported to the ASRS. Clinical and imaging characteristics were reviewed for evidence of retinal vasculitis and analyzed. Results: Fourteen eyes of 13 patients were confirmed to have retinal vasculitis by review of imaging studies. All cases occurred after the first pegcetacoplan injection. Occlusive retinal vasculopathy was confirmed in 11 eyes (79%). Patients presented a median of 10.5 days (range, 8-23 days) after pegcetacoplan injection. All eyes had anterior chamber inflammation, and 12 eyes (86%) had vitritis. Vasculopathy involved retinal veins (100%) more than arteries (73%), and 12 eyes (86%) had retinal hemorrhages. The median visual acuity (VA) was 20/60 (range, 20/30-5/200) at baseline, 20/300 (range, 20/100-no light perception [NLP]) at vasculitis presentation, and 20/200 (range 20/70-NLP) at the last follow-up. Eight eyes (57%) had more than a 3-line decrease in VA, and 6 eyes (43%) had more than a 6-line decrease in VA from baseline to the final follow-up, including 2 eyes that were enucleated. Six eyes (43%) developed signs of anterior segment neovascularization. Conclusions: There is currently no known etiology for vasculitis in this series. Optimum treatment strategies remain unknown. Infectious etiologies should be considered, and corticosteroid treatments may hasten resolution of inflammatory findings. Continued treatment of affected patients with pegcetacoplan should be avoided.},
}
@article {pmid38223780,
year = {2024},
author = {Gupta, M and Lean, J},
title = {Full-Thickness Macular Hole Caused by Acute Subretinal Hemorrhage From Wet Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {1},
pages = {82-85},
pmid = {38223780},
issn = {2474-1272},
abstract = {Purpose: To present a case of full-thickness macular hole (MH) that developed in association with acute subretinal hemorrhage from wet age-related macular degeneration (AMD). Methods: A retrospective observational review of a single case was performed. Results: An 84-year-old man with wet AMD presented with central vision loss and floaters and was noted to have a subretinal hemorrhage and an associated MH, which subsequently progressed to MH-associated macular detachment. The patient had a pars plana vitrectomy with internal limiting membrane peeling, gas tamponade, and prone positioning, resulting in closure of the MH and improvement in visual acuity. Conclusions: A full-thickness MH developed as a result of foveal dehiscence from an acute hemorrhage caused by choroidal neovascularization in wet AMD.},
}
@article {pmid38223766,
year = {2024},
author = {Cheng, BT and Kim, AB and Lyon, AT and Mirza, RG},
title = {Disease Awareness Among Patients With Age-Related Macular Degeneration: Patterns and Predictors.},
journal = {Journal of vitreoretinal diseases},
volume = {8},
number = {1},
pages = {58-66},
pmid = {38223766},
issn = {2474-1272},
abstract = {Purpose: To examine the prevalence and predictors of patient awareness of their disease in adults with age-related macular degeneration (AMD). Methods: This study analyzed 5553 adults 40 years or older in the 2005-2008 National Health and Nutrition Examination Survey who underwent retinal imaging. AMD was determined based on retinal images. Patient awareness of their AMD was assessed by a self-reported AMD diagnosis. Multivariable logistic regression models were constructed to examine the association of patient awareness of their AMD with sociodemographic characteristics and specific AMD lesion types on retinal imaging. Results: AMD was identified in 425 of the adults surveyed (6.5%) (95% confidence interval [CI], 5.5%-7.5%), including 87.7% (95% CI, 82.9%-92.5%) with early AMD and 12.3% (95% CI, 7.5%-17.1%) with late AMD. Among adults with either type of AMD on retinal imaging, 17.5% (95% CI, 13.1%-22.0%) were aware of their disease, which included 11.6% (95% CI, 8.4%-14.9%) with early AMD and 59.2% (95% CI, 43.1%-75.3%) with late AMD (P < .0001). In the same group, those aged 60 years or older (odds ratio [OR], 33.46; 95% CI, 7.67-146.03) and with a best-corrected visual acuity of 20/40 or worse (OR, 4.63; 95% CI, 2.95-7.26) had higher awareness of their AMD diagnosis, whereas Hispanic (OR, 0.28; 95% CI, 0.09-0.88) vs White adults and those who did not speak English at home (OR, 0.05; 95% CI, 0.01-0.41) had lower awareness of their diagnosis. Conclusions: Fewer than 1 in 5 adults with AMD were aware of their personal diagnosis, including fewer than 3 in 5 adults with late AMD. Older adults and those with worse vision were more likely to know they have AMD, whereas Hispanic adults and those who did not speak English at home were less likely. Efforts to increase patients' awareness of their AMD may improve rates of follow-up and prevent vision loss.},
}
@article {pmid38223170,
year = {2024},
author = {Lu, J and Cheng, Y and Hiya, FE and Shen, M and Herrera, G and Zhang, Q and Gregori, G and Rosenfeld, PJ and Wang, RK},
title = {Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.},
journal = {Biomedical optics express},
volume = {15},
number = {1},
pages = {413-427},
pmid = {38223170},
issn = {2156-7085},
support = {R01 EY028753/EY/NEI NIH HHS/United States ; },
abstract = {Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.},
}
@article {pmid38222454,
year = {2023},
author = {Liu, W and Zhu, X and Ge, X and Chen, Y and Li, DW and Gong, L},
title = {Light damage induces inflammatory factors in mouse retina and vitreous humor.},
journal = {Molecular vision},
volume = {29},
number = {},
pages = {180-187},
pmid = {38222454},
issn = {1090-0535},
mesh = {Mice ; Humans ; Animals ; *Retinal Degeneration/genetics ; Vitreous Body/metabolism ; Retina/metabolism ; *Retinitis Pigmentosa/genetics/pathology ; Inflammation/pathology ; Disease Models, Animal ; Inflammation Mediators ; },
abstract = {PURPOSE: Increased inflammatory factor levels have been reported in the vitreous humor (VH) of diabetic retinopathy and neovascular age-related macular degeneration, ocular diseases generally associated with the formation of new retinal blood vessels and leakage. However, the levels of inflammatory mediators are less known in retinal degeneration without neovascularization. Human retinitis pigmentosa (RP) and animal models of light-induced retinal degeneration (LIRD) share several features, such as photoreceptor death and retinal inflammation. Here, we aimed to determine the levels of inflammatory factors in the VH of the LIRD mouse model.<br><br>METHODS: LIRD was induced by exposing BALB/c mice to white light (15,000&#xa0;lx, 2 h), and the mice were recovered for 2 days before analysis (n = 50 mice). We assessed retinal morphology using optical coherence tomography and hematoxylin and eosin staining; retinal cell viability was determined using terminal deoxynucleotidyl transferase dUTP nick-end labeling, and retinal responses were measured based on electroretinogram signals. Total retinal RNAs were extracted and subjected to RNA sequencing analysis. VH samples from control (n = 4) and LIRD mice (n = 9) were assayed in triplicate for a panel of four inflammatory mediators using the Simple Plex Cartridge on an Ella System.<br><br>RESULTS: Retinal degeneration, photoreceptor death, infiltration of microglia/macrophages into the photoreceptor layer, and loss of a- and b-waves were obviously detected after LIRD. RNA sequencing revealed that light damage (LD) led to the significant upregulation of inflammatory factors in mouse retinas. In the VH, LD increased the total protein concentration. Dramatic induction of CCL2 (~3000 fold) and IL6 (~10 fold) was detected in VH in response to LD. Increased but not significant levels of TNF&#x3b1; and IL1&#x3b2; were also detected in light-exposed VH.<br><br>CONCLUSIONS: Given that the LIRD model mimics RP pathogenesis in some aspects, these results suggest a causative link between retinal degeneration and VH inflammation in RP progression, and the increased CCL2 level in VH may reflect similar elevated CCL2 expression in the degenerative retina.},
}
@article {pmid38221852,
year = {2025},
author = {Koçyiğit, E and Gövez, NE and Arslan, S and Ağagündüz, D},
title = {A narrative review on dietary components and patterns and age-related macular degeneration.},
journal = {Nutrition research reviews},
volume = {38},
number = {1},
pages = {143-170},
doi = {10.1017/S0954422424000015},
pmid = {38221852},
issn = {1475-2700},
mesh = {Humans ; *Macular Degeneration/prevention &amp; control/etiology/epidemiology ; *Diet ; Diet, Mediterranean ; Gastrointestinal Microbiome ; Oxidative Stress ; Fruit ; Vegetables ; Seafood ; },
abstract = {Age-related macular degeneration (AMD) is one of the most prevalent eye diseases among the ageing population worldwide. It is a leading cause of blindness in individuals over 55, particularly in industrialised Western countries. The prevalence of AMD increases with age, and genetic factors and environmental influences are believed to contribute to its development. Among the environmental factors, diet plays a significant role in AMD. This review explores the association between dietary components, dietary patterns and AMD. Various nutrients, non-nutrient substances and dietary models that have the potential to counteract oxidative stress and inflammation, which are underlying mechanisms of AMD, are discussed. Consuming fruits, vegetables, fish and seafood, whole grains, olive oil, nuts and low-glycaemic-index foods has been highlighted as beneficial for reducing the risk of AMD. Adhering to the Mediterranean diet, which encompasses these elements, can be recommended as a dietary pattern for AMD. Furthermore, the modulation of the gut microbiota through dietary interventions and probiotics has shown promise in managing AMD.},
}
@article {pmid38219789,
year = {2024},
author = {Hollaus, M and Iby, J and Brugger, J and Leingang, O and Reiter, GS and Schmidt-Erfurth, U and Sacu, S},
title = {Influence of drusenoid pigment epithelial detachments on the progression of age-related macular degeneration and visual acuity.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {59},
number = {6},
pages = {417-423},
doi = {10.1016/j.jcjo.2023.12.007},
pmid = {38219789},
issn = {1715-3360},
mesh = {Humans ; *Visual Acuity/physiology ; Prospective Studies ; Female ; *Tomography, Optical Coherence/methods ; Male ; Aged ; *Fluorescein Angiography/methods ; *Disease Progression ; *Retinal Drusen/diagnosis/physiopathology ; *Retinal Detachment/diagnosis/physiopathology/etiology ; *Retinal Pigment Epithelium/pathology ; Fundus Oculi ; Aged, 80 and over ; Follow-Up Studies ; Middle Aged ; Macular Degeneration/diagnosis/complications/physiopathology ; },
abstract = {OBJECTIVE: To analyze the presence and morphologic characteristics of drusenoid pigment epithelial detachments (DPEDs) in spectral-domain optical coherence tomography (SD-OCT) in Caucasian patients with early and intermediate age-related macular degeneration (AMD) as well as the influence of these characteristics on best-corrected visual acuity (BCVA) and disease progression.<br><br>DESIGN: Prospective observational cohort study.<br><br>PARTICIPANTS: 89 eyes of 56 patients with early and intermediate AMD.<br><br>METHODS: Examinations consisted of BCVA, SD-OCT, and indocyanine green angiography. Evaluated parameters included drusen type, mean drusen height and -volume, the presence of DPED, DPED maximum height, -maximum diameter, -volume, topographic location, the rate of DPED collapse, and the development of macular neovascularization (MNV) or geographic atrophy (GA).<br><br>RESULTS: DPED maximum height (162.34 &#xb5;m &#xb1; 75.70 &#x3bc;m, p&#x202f;=&#x202f;0.019) was significantly associated with the development of GA and MNV. For each additional 100 &#x3bc;m in maximum height, the odds of developing any late AMD (GA or MNV) increased by 2.23 (95% CI&#x202f;=&#x202f;1.14-4.35). The presence of DPED (44 eyes, p&#x202f;=&#x202f;0.01), its volume (0.20 mm &#xb1; 0.20 mm, p&#x202f;=&#x202f;0.01), maximum diameter (1860.87 &#x3bc;m &#xb1; 880.74 &#x3bc;m, p&#x202f;=&#x202f;0.03), maximum height (p < 0.001) and topographical location in the central millimetre (p&#x202f;=&#x202f;0.004) of the Early Treatment Diabetic Retinopathy Study (ETDRS)-Grid were significantly correlated with BCVA at the last follow-up (0.15logMAR &#xb1; 0.20logMAR; Snellen equivalent approximately 20/28). DPEDs occurred significantly less in the outer quadrants than in the central millimetre and inner quadrants of ETDRS-Grid (all p values < 0.001).<br><br>CONCLUSIONS: The height of drusen and DPEDs is a biomarker that is significantly associated with the development of late AMD and visual loss. DPEDs affect predominantly the center and inner quadrants of the ETDRS-Grid.},
}
@article {pmid38218678,
year = {2024},
author = {Fliesler, SJ},
title = {The subretinal drusenoid deposit (SDD) of age-related macular degeneration (AMD) may have a specific and strong association with high-risk vascular diseases (HRVDs).},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {13},
number = {1},
pages = {100035},
doi = {10.1016/j.apjo.2024.100035},
pmid = {38218678},
issn = {2162-0989},
mesh = {Humans ; *Macular Degeneration ; Fluorescein Angiography ; *Vascular Diseases/complications ; Tomography, Optical Coherence ; },
}
@article {pmid38216049,
year = {2024},
author = {Enríquez-Fuentes, JE and Oribio-Quinto, C and Pascual-Santiago, MA and Alarcón-García, AD and Fernández-Vigo, JI},
title = {Long-term results of treatment of neovascular age-related macular degeneration using antiangiogenic drugs: A review of the literature.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {99},
number = {5},
pages = {195-204},
doi = {10.1016/j.oftale.2024.01.005},
pmid = {38216049},
issn = {2173-5794},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Visual Acuity ; Treatment Outcome ; Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Wet Macular Degeneration/drug therapy ; Time Factors ; Aged ; Follow-Up Studies ; },
abstract = {Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA > 70 letters. The 67.9% of patients remained stable at the end of follow-up (< 15 letter loss), with a severe loss (≥ 15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.},
}
@article {pmid38214731,
year = {2024},
author = {Märker, DA and Radeck, V and Lehmann, F and Barth, T and Helbig, H and Eter, N and Alten, F and Clemens, CR},
title = {[Iatrogenic retinal defects after intravitreal operative drug injections].},
journal = {Die Ophthalmologie},
volume = {121},
number = {2},
pages = {129-134},
pmid = {38214731},
issn = {2731-7218},
mesh = {Humans ; Aged ; Intravitreal Injections ; *Retinal Diseases/drug therapy ; *Eye Diseases/drug therapy ; *Retinal Detachment/surgery ; Iatrogenic Disease ; },
abstract = {BACKGROUND: Intravitreal operative drug injections represent one of the most frequently performed medical interventions. The risk profile is low. In addition to intraocular pressure elevation, the most frequent complications include exogenous endophthalmitis, vitreous hemorrhage and rhegmatogenous retinal detachment. Furthermore, isolated cases of lens injuries, macular holes associated with vitreoretinal traction and peripheral retinal defects have been described. In the present case series sharp iatrogenic macular and retinal defects are described.<br><br>METHODS: Retrospective multicenter case collection of patients with iatrogenic retinal defects after intravitreal injections from 2016 to 2023.<br><br>RESULTS: Iatrogenic retinal trauma after intravitreal injections for treatment of neovascular age-related macular degeneration was identified in 9 cases (72&#xa0;years&#x202f;&#xb1;&#x2009;8.1, 3&#xa0;eyes pseudophakic). While sharp injuries within the macula occurred in six cases, extramacular lesions were detected in the other cases.<br><br>CONCLUSION: Iatrogenic retinal and macular injuries are rare complications of intravitreal injections and when correctly carried out are preventable, especially with respect to use of cannulas and the choice of the distance from the limbus.},
}
@article {pmid38214056,
year = {2024},
author = {Vidal-Oliver, L and Montolío-Marzo, E and Gallego-Pinazo, R and Dolz-Marco, R},
title = {Optical coherence tomography biomarkers in early and intermediate age-related macular degeneration: A clinical guide.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {2},
pages = {207-219},
doi = {10.1111/ceo.14337},
pmid = {38214056},
issn = {1442-9071},
mesh = {Humans ; Aged ; *Retinal Drusen/diagnosis ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnosis ; *Geographic Atrophy/diagnosis ; Biomarkers ; },
abstract = {Advanced forms of age-related macular degeneration (AMD), characterised by atrophic and neovascular changes, are a leading cause of vision loss in the elderly population worldwide. Prior to the development of advanced AMD, a myriad of risk factors from the early and intermediate stages of AMD have been published in the scientific literature over the last years. The ability to precisely recognise structural and anatomical changes in the ageing macula, altogether with the understanding of the individual risk implications of each one of them is key for an accurate and personalised diagnostic assessment. The present review aims to summarise updated evidence of the relative risk conferred by diverse macular signs, commonly seen on optical coherence tomography, in terms of progression to geographic atrophy or macular neovascularization. This information may also serve as a basis for tailored follow-up monitoring visits.},
}
@article {pmid38212259,
year = {2024},
author = {},
title = {Avacincaptad pegol (Izervay) for geographic atrophy in age-related macular degeneration.},
journal = {The Medical letter on drugs and therapeutics},
volume = {66},
number = {1694},
pages = {15-16},
doi = {10.58347/tml.2024.1694d},
pmid = {38212259},
issn = {1523-2859},
mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy ; *Macular Degeneration/diagnosis/drug therapy ; },
}
@article {pmid38206782,
year = {2024},
author = {Morano, J and Aresta, G and Grechenig, C and Schmidt-Erfurth, U and Bogunovic, H},
title = {Deep Multimodal Fusion of Data With Heterogeneous Dimensionality via Projective Networks.},
journal = {IEEE journal of biomedical and health informatics},
volume = {28},
number = {4},
pages = {2235-2246},
doi = {10.1109/JBHI.2024.3352970},
pmid = {38206782},
issn = {2168-2208},
mesh = {Humans ; *Retina ; *Tomography, X-Ray Computed/methods ; Image Processing, Computer-Assisted/methods ; },
abstract = {The use of multimodal imaging has led to significant improvements in the diagnosis and treatment of many diseases. Similar to clinical practice, some works have demonstrated the benefits of multimodal fusion for automatic segmentation and classification using deep learning-based methods. However, current segmentation methods are limited to fusion of modalities with the same dimensionality (e.g., 3D + 3D, 2D + 2D), which is not always possible, and the fusion strategies implemented by classification methods are incompatible with localization tasks. In this work, we propose a novel deep learning-based framework for the fusion of multimodal data with heterogeneous dimensionality (e.g., 3D + 2D) that is compatible with localization tasks. The proposed framework extracts the features of the different modalities and projects them into the common feature subspace. The projected features are then fused and further processed to obtain the final prediction. The framework was validated on the following tasks: segmentation of geographic atrophy (GA), a late-stage manifestation of age-related macular degeneration, and segmentation of retinal blood vessels (RBV) in multimodal retinal imaging. Our results show that the proposed method outperforms the state-of-the-art monomodal methods on GA and RBV segmentation by up to 3.10% and 4.64% Dice, respectively.},
}
@article {pmid38205491,
year = {2023},
author = {Murkey, SP and Agarwal, A and Pandit, P and Kumar, S and Jaiswal, A},
title = {Unveiling the Spectrum of Ophthalmic Manifestations in Nutritional Deficiencies: A Comprehensive Review.},
journal = {Cureus},
volume = {15},
number = {12},
pages = {e50311},
pmid = {38205491},
issn = {2168-8184},
abstract = {This comprehensive review explores the intricate relationship between nutrition and ocular health, focusing on the crucial roles of essential nutrients like Vitamin A, Vitamin B1 (thiamine), Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Zinc, and Folate (Vitamin B9) in maintaining eye well-being. Nutrient deficiencies have significant consequences, leading to various eye-related issues, from night blindness to age-related conditions such as cataracts and macular degeneration. It is imperative to address these deficiencies, emphasizing the importance of a well-rounded diet with the necessary nutrients. When necessary, supplementation and regular eye examinations are vital components for effectively monitoring ocular health. Public health campaigns and educational initiatives also play a key role in raising awareness about the profound impact of nutrition on eye health. Future research should explore personalized nutrition plans, nutrigenomics, longitudinal studies, and targeted nutritional interventions. Such investigations will not only enhance our understanding of this crucial connection but also have the potential to reduce the global burden of eye diseases.},
}
@article {pmid38205100,
year = {2024},
author = {Chu, L and Bi, C and Wang, C and Zhou, H},
title = {The Relationship between Complements and Age-Related Macular Degeneration and Its Pathogenesis.},
journal = {Journal of ophthalmology},
volume = {2024},
number = {},
pages = {6416773},
pmid = {38205100},
issn = {2090-004X},
abstract = {Age-related macular degeneration is a retinal disease that causes permanent loss of central vision in people over the age of 65. Its pathogenesis may be related to mitochondrial dysfunction, inflammation, apoptosis, autophagy, complement, intestinal flora, and lipid disorders. In addition, the patient's genes, age, gender, cardiovascular disease, unhealthy diet, and living habits may also be risk factors for this disease. Complement proteins are widely distributed in serum and tissue fluid. In the early 21st century, a connection was found between the complement cascade and age-related macular degeneration. However, little is known about the effect of complement factors on the pathogenesis of age-related macular degeneration. This article reviews the factors associated with age-related macular degeneration, the relationship between each factor and complement, the related functions, and variants and provides new ideas for the treatment of this disease.},
}
@article {pmid38203675,
year = {2023},
author = {Rozanowska, M and Edge, R and Land, EJ and Navaratnam, S and Sarna, T and Truscott, TG},
title = {Scavenging of Cation Radicals of the Visual Cycle Retinoids by Lutein, Zeaxanthin, Taurine, and Melanin.},
journal = {International journal of molecular sciences},
volume = {25},
number = {1},
pages = {},
pmid = {38203675},
issn = {1422-0067},
support = {/WT_/Wellcome Trust/United Kingdom ; Travelling Wellcome Fellowship To M. Rozanowska/WT_/Wellcome Trust/United Kingdom ; },
mesh = {*Retinoids ; *Vitamin A ; Melanins ; Retinaldehyde ; Lutein ; Zeaxanthins ; Taurine ; Cations ; },
abstract = {In the retina, retinoids involved in vision are under constant threat of oxidation, and their oxidation products exhibit deleterious properties. Using pulse radiolysis, this study determined that the bimolecular rate constants of scavenging cation radicals of retinoids by taurine are smaller than 2 × 10[7] M[-1]s[-1] whereas lutein scavenges cation radicals of all three retinoids with the bimolecular rate constants approach the diffusion-controlled limits, while zeaxanthin is only 1.4-1.6-fold less effective. Despite that lutein exhibits greater scavenging rate constants of retinoid cation radicals than other antioxidants, the greater concentrations of ascorbate in the retina suggest that ascorbate may be the main protectant of all visual cycle retinoids from oxidative degradation, while α-tocopherol may play a substantial role in the protection of retinaldehyde but is relatively inefficient in the protection of retinol or retinyl palmitate. While the protection of retinoids by lutein and zeaxanthin appears inefficient in the retinal periphery, it can be quite substantial in the macula. Although the determined rate constants of scavenging the cation radicals of retinol and retinaldehyde by dopa-melanin are relatively small, the high concentration of melanin in the RPE melanosomes suggests they can be scavenged if they are in proximity to melanin-containing pigment granules.},
}
@article {pmid38202302,
year = {2024},
author = {Strzalka-Mrozik, B and Paprzycka, O and Gruszka, O and Madej, M and Kruszniewska-Rajs, C and Gola, JM and Turek, A},
title = {Ranibizumab Modifies the Expression of Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Mononuclear Cells in Patients with Exudative Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {1},
pages = {},
pmid = {38202302},
issn = {2077-0383},
support = {PCN-1-049/N/2/F//Medical University of Silesia/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in people over 60 years of age. Despite research, the causes of AMD remain unclear. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are known to be involved in AMD development, and anti-vascular endothelial growth factor therapy has revolutionized its treatment. This study aims to analyze the changes in gene expression in MMPs and TIMPS in patients with neovascular AMD before and after three doses of ranibizumab.<br><br>METHODS: The study involved 29 patients with neovascular AMD treated with ranibizumab. Peripheral blood mononuclear cells were collected before treatment and 24 h after the third dose of ranibizumab. We assessed MMP and TIMP gene expression profiles through oligonucleotide microarrays and validated selected differential genes using RT-qPCR.<br><br>RESULTS: A statistically significant change in the expression of six MMP- and TIMP-related genes was observed using oligonucleotide microarray. The mRNA levels of the two genes with the most significant fold changes, MMP15 and TIMP2, were then quantified using RT-qPCR. The results confirmed a statistically significant increase in MMP15 expression and a decrease in TIMP2 levels, although this change was not statistically significant in the group before and after the third dose of ranibizumab.<br><br>CONCLUSION: Ranibizumab affects the systemic expression of MMP and TIMP-related genes in patients with neovascular AMD. Results from our exploratory study suggest that MMP15, in particular, may play a role in the treatment response, but further research is necessary.},
}
@article {pmid38202151,
year = {2023},
author = {Wong, DHT and Li, KKW},
title = {Fixed Quarterly Dosing of Aflibercept after Loading Doses in Neovascular Age-Related Macular Degeneration in Chinese Eyes.},
journal = {Journal of clinical medicine},
volume = {13},
number = {1},
pages = {},
pmid = {38202151},
issn = {2077-0383},
abstract = {We aimed to investigate the success rate of planned fixed quarterly aflibercept injections after three loading doses (QDA3L) to achieve stability without recurrence in neovascular age-related macular degeneration (nAMD) at a tertiary eye centre. A retrospective study was conducted over five years (2017-2021) by including all consecutive cases of nAMD treated with three initial aflibercept injections four weeks apart, followed by planned injection appointments every 12 to 16 weeks starting from week 20. The primary endpoint was to determine the proportion of patients who maintained disease inactivity at week 52 and week 104. A total of 40 eyes of 40 patients were included. The overall mean age was 80.8, with a male preponderance. The overall success rate in our study population was 52.9% and 53.6% at week 52 and week 104, respectively. The fovea remained dry at 85.3% at week 52 and 82.1% at week 104, and 85.3% and 85.7% of subjects lost fewer than 15 ETDRS letters at week 52 and week 104, respectively. While this study does not suggest the superiority of this regimen, the success and failure rates obtained in our study can be used in the counselling process for this particular fixed treatment regimen for nAMD.},
}
@article {pmid38202118,
year = {2023},
author = {Gershoni, A and Barayev, E and Daood, RH and Yogev, M and Gal-Or, O and Reitblat, O and Tsessler, M and Schaap Fogler, M and Tuuminen, R and Ehrlich, R},
title = {Anatomical and Functional Outcomes with Prompt versus Delayed Initiation of Anti-VEGF in Exudative Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {13},
number = {1},
pages = {},
pmid = {38202118},
issn = {2077-0383},
abstract = {PURPOSE: To investigate the correlation between time from diagnosis of treatment-naïve exudative age-related macular degeneration (AMD) to the introduction of anti-VEGF treatment and anatomical and functional outcomes.<br><br>DESIGN: Retrospective cohort study.<br><br>METHODS: Included were treatment-na&#xef;ve exudative AMD patients who presented to a single tertiary medical center between 2012 and 2018. All patients were treated within the first 30 days of their diagnosis with three monthly intravitreal injections of bevacizumab. Patients were divided into three groups: group 1 (prompt anti-VEGF) were injected with bevacizumab within ten days, group 2 (intermediate anti-VEGF) within 11-20 days, and group 3 (delayed anti-VEGF) within 21-30 days from diagnosis. Baseline characteristics and clinical outcomes were compared up to two years from treatment.<br><br>RESULTS: 146 eyes of 146 patients were included. Sixty-eight patients were in the prompt anti-VEGF group, 31 in the intermediate anti-VEGF group, and 47 in the delayed anti-VEGF group. Following the induction phase of three intravitreal bevacizumab injections, the mean central subfield macular thickness (328.0 &#xb1; 115.4 &#xb5;m vs. 364.6 &#xb1; 127.2 &#xb5;m vs. 337.7 &#xb1; 150.1 &#xb5;m, p = 0.432) and the best-corrected visual acuity (0.47 &#xb1; 0.38 vs. 0.59 &#xb1; 0.48 vs. 0.47 &#xb1; 0.44 logMAR units, p = 0.458) were comparable between the prompt, intermediate and delayed anti-VEGF groups. Anatomical and functional outcomes, treatment burden, number of relapses and eyes with second-line anti-VEGF therapy were comparable between the groups at both 1-year and 2-year timepoints.<br><br>CONCLUSIONS: Our real-world evidence data emphasize that even if anti-VEGF induction cannot be initiated promptly within ten days from diagnosis of na&#xef;ve exudative AMD, the visual and anatomical prognosis of the patients may not worsen if the treatment is started within one month of diagnosis.},
}
@article {pmid38202083,
year = {2023},
author = {Mastropasqua, R and Gironi, M and D'Aloisio, R and Pastore, V and Boscia, G and Vecchiarino, L and Perna, F and Clemente, K and Palladinetti, I and Calandra, M and Piepoli, M and Porreca, A and Di Nicola, M and Boscia, F},
title = {Intraoperative Iridectomy in Femto-Laser Assisted Smaller-Incision New Generation Implantable Miniature Telescope.},
journal = {Journal of clinical medicine},
volume = {13},
number = {1},
pages = {},
pmid = {38202083},
issn = {2077-0383},
abstract = {BACKGROUND: In this study, we aimed to report the short-term (6 months) effects on visual functionality and safety of femto-laser assisted smaller-incision new-generation implantable miniature telescope (SING-IMT™) implanting, particularly related to postsurgical intraocular pressure increase, in patients suffering from end-stage age-related macular degeneration (AMD) and cataract. This device, designed for monocular use, aims to minimise the impact of the central scotoma by projecting the images onto a larger area of the photoreceptors surrounding the macula.<br><br>METHODS: In this prospective multicentric observational case series study, 6 eyes of 6 patients who underwent SING-IMT&#x2122; implantations were enrolled. At baseline and 6 months follow-up, best corrected distance visual acuity (BCDV) and best corrected near visual acuity (BCNVA), intraocular pressure (IOP), anterior chamber depth, endothelial cells count were assessed. In addition, IOP was also measured at 7, 15, 30, 45 days, and at 3 months follow-up. Finally, the incidence of complications was evaluated.<br><br>RESULTS: At final follow-up, in the study eyes, mean BCDVA improved by +10.0 letters (6.25; 13.8) letters and mean BCNVA improved by -0.30 logMAR (-0.55; -0.20). At postoperative month 6, we reported a mean IOP decrease of 4.50 mmHg (-5.75; -0.25). Interestingly, 83.3% of patients had an increased IOP value in at least one of the first two postoperative follow-ups (7 days and 15 days). In patients in whom intraoperative mechanical iridotomy was not performed, it was necessary to perform a postoperative YAG laser iridotomy to improve IOP management. Compared to the baseline, ECD loss at 6 months follow-up was 12.6%.<br><br>CONCLUSIONS: The SING IMT&#x2122; device was found to be effective in the distance and near vision improvement, without serious postoperative complications. We recommend intraoperative mechanical iridectomy in order to easily manage post-operative IOP and to avoid sudden IOP rise with its possible consequences. These good results can be a hope to partially improve the quality of life of patients suffering from severe end stage macular atrophy.},
}
@article {pmid38201254,
year = {2023},
author = {Malih, S and Song, YS and Sorenson, CM and Sheibani, N},
title = {Choroidal Mast Cells and Pathophysiology of Age-Related Macular Degeneration.},
journal = {Cells},
volume = {13},
number = {1},
pages = {},
pmid = {38201254},
issn = {2073-4409},
support = {P30 EY016665/EY/NEI NIH HHS/United States ; R01 EY030076/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Humans ; Mast Cells ; *Macular Degeneration ; Choroid ; Retina ; *Retinal Degeneration ; },
abstract = {Age-related macular degeneration (AMD) remains a leading cause of vision loss in elderly patients. Its etiology and progression are, however, deeply intertwined with various cellular and molecular interactions within the retina and choroid. Among the key cellular players least studied are choroidal mast cells, with important roles in immune and allergic responses. Here, we will review what is known regarding the pathophysiology of AMD and expand on the recently proposed intricate roles of choroidal mast cells and their activation in outer retinal degeneration and AMD pathogenesis. We will focus on choroidal mast cell activation, the release of their bioactive mediators, and potential impact on ocular oxidative stress, inflammation, and overall retinal and choroidal health. We propose an important role for thrombospondin-1 (TSP1), a major ocular angioinflammatory factor, in regulation of choroidal mast cell homeostasis and activation in AMD pathogenesis. Drawing from limited studies, this review underscores the need for further comprehensive studies aimed at understanding the precise roles changes in TSP1 levels and choroidal mast cell activity play in pathophysiology of AMD. We will also propose potential therapeutic strategies targeting these regulatory pathways, and highlighting the promise they hold for curbing AMD progression through modulation of mast cell activity. In conclusion, the evolving understanding of the role of choroidal mast cells in AMD pathogenesis will not only offer deeper insights into the underlying mechanisms but will also offer opportunities for development of novel preventive strategies.},
}
@article {pmid38200010,
year = {2024},
author = {Zouache, MA and Richards, BT and Pappas, CM and Anstadt, RA and Liu, J and Corsetti, T and Matthews, S and Seager, NA and Schmitz-Valckenberg, S and Fleckenstein, M and Hubbard, WC and Thomas, J and Hageman, JL and Williams, BL and Hageman, GS},
title = {Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {443},
pmid = {38200010},
issn = {2041-1723},
support = {R24 EY017404/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Bruch Membrane ; Choroid ; Cognition ; *Complement Factor H/genetics ; *Macular Degeneration/genetics ; },
abstract = {Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch's membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD.},
}
@article {pmid38198613,
year = {2024},
author = {Fernández-Vigo, JI and López-Guajardo, L and Dolz-Marco, R and Donate-López, J},
title = {Multilayered Exudative Bacillary Layer Detachment in Active Choroidal Neovascularization: A New Optical Coherence Tomography Sign.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {55},
number = {2},
pages = {92-94},
doi = {10.3928/23258160-20231207-01},
pmid = {38198613},
issn = {2325-8179},
mesh = {Humans ; Aged ; Tomography, Optical Coherence/methods ; *Bacillus ; *Choroidal Neovascularization/diagnosis ; Retina ; Fluorescein Angiography/methods ; Retrospective Studies ; },
abstract = {In this article, we present three cases diagnosed with active choroidal neovascularization (CNV): two cases diagnosed with neovascular age-related macular degeneration (nAMD), and one case with myopic CNV in an elderly eye that presented a characteristic and unique optical coherence tomography (OCT) sign consisting of well-defined, circular-shaped multiple concentric layers of alternating iso-hyperreflective material located between the external limiting membrane and outer photoreceptor layers, which seems to be a multilayered bacillary layer detachment (BALAD). Multilayered exudative BALAD in active CNV may be a new and characteristic OCT sign. [Ophthalmic Surg Lasers Imaging Retina 2024;55:92-94.].},
}
@article {pmid38198053,
year = {2024},
author = {Korobelnik, JF and Chaudhary, V and Mitchell, P and Kang, SW and Tadayoni, R and Allmeier, H and Lee, J and Zhang, X and Machewitz, T and Bailey, C},
title = {XTEND: Two-Year Results from a Global Observational Study Investigating Proactive Dosing of Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {3},
pages = {725-738},
pmid = {38198053},
issn = {2193-8245},
abstract = {INTRODUCTION: XTEND (NCT03939767) is a multicenter, observational, prospective study of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in routine clinical practice. The study aims to examine treatment outcomes of proactive intravitreal aflibercept (IVT-AFL) treatment regimens (fixed dosing or treat-and-extend) according to local marketing labels.<br><br>METHODS: Study eyes received IVT-AFL injections as per the local label. The mean changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to month (M) 12 and M24 were measured and stratified by baseline factors. Treatment exposure and safety data were evaluated. Statistical analysis was descriptive.<br><br>RESULTS: Overall, 1466 patients from 17 countries were treated. For the overall population, the mean&#x2009;&#xb1;&#x2009;standard deviation (SD) age was 78.7&#x2009;&#xb1;&#x2009;8.5 (range 50-100)&#xa0;years, and 891 patients (60.8%) were female. The mean&#x2009;&#xb1;&#x2009;SD baseline BCVA was 54.3&#x2009;&#xb1;&#x2009;20.3 letters and CST was 374&#x2009;&#xb1;&#x2009;126&#xa0;&#xb5;m. At M12 and M24, mean (95% confidence interval [CI]) BCVA change was&#x2009;+ 4.3 (3.4, 5.3) and&#x2009;+&#x2009;2.3 (1.3, 3.3) letters, respectively. Mean (95% CI) CST was&#x2009;-&#x2009;106 (-&#x2009;114,&#x2009;-&#x2009;99) &#x3bc;m and&#x2009;-&#x2009;109 (-&#x2009;117,&#x2009;-&#x2009;102) &#x3bc;m at M12 and M24, respectively. At M24, 41.5% of patients had a BCVA&#x2009;&#x2265;&#x2009;70 letters. Patients received a mean&#x2009;&#xb1;&#x2009;SD of 7.7&#x2009;&#xb1;&#x2009;2.7 injections by M12 and 10.8&#x2009;&#xb1;&#x2009;5.0 injections by M24 (3.1 injections between M12 and M24). Adverse events were consistent with the known safety profile of IVT-AFL.<br><br>CONCLUSION: The 24-month results indicate that, in routine clinical practice, a proactive IVT-AFL regimen achieves functional improvements in patients with treatment-na&#xef;ve nAMD. The proportion of patients achieving&#x2009;&#x2265;&#x2009;70 letters at M24 increased, and patients with baseline BCVA&#x2009;&#x2265;&#x2009;70 letters maintained vision regardless of the followed IVT-AFL label.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03939767. A video abstract is available for this article. Supplementary file2 (MP4 364624 KB).},
}
@article {pmid38195611,
year = {2024},
author = {Kwon, C and Cho, W and Choi, SW and Oh, H and Abd El-Aty, AM and Gecili, I and Jeong, JH and Jung, TW},
title = {DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {38},
pmid = {38195611},
issn = {1479-5876},
support = {2022R1A2B5B01001453//National Research Foundation (KR)/ ; },
mesh = {Humans ; *AMP-Activated Protein Kinases ; Caspase 3 ; Tunicamycin/pharmacology ; Vascular Endothelial Growth Factor A ; *Macular Degeneration/therapy ; Myokines ; Epithelial Cells ; Retinal Pigments ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells.<br><br>METHODS: We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining.<br><br>RESULTS: Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor.<br><br>CONCLUSIONS: Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.},
}
@article {pmid38193957,
year = {2024},
author = {Fleckenstein, M and Schmitz-Valckenberg, S and Chakravarthy, U},
title = {Age-Related Macular Degeneration: A Review.},
journal = {JAMA},
volume = {331},
number = {2},
pages = {147-157},
doi = {10.1001/jama.2023.26074},
pmid = {38193957},
issn = {1538-3598},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY033365/EY/NEI NIH HHS/United States ; R01 EY034965/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Humans ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage/pharmacology/therapeutic use ; Intravitreal Injections ; *Macular Degeneration/diagnosis/drug therapy/epidemiology/etiology ; Prospective Studies ; Retina/drug effects/pathology ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; },
abstract = {IMPORTANCE: Age-related macular degeneration (AMD) affects approximately 20 million people in the US and 196 million people worldwide. AMD is a leading cause of severe vision impairment in older people and is expected to affect approximately 288 million people worldwide by 2040.<br><br>OBSERVATIONS: Older age, genetic factors, and environmental factors, such as cigarette smoking, are associated with development of AMD. AMD occurs when extracellular deposits accumulate in the outer retina, ultimately leading to photoreceptor degeneration and loss of central vision. The late stages of AMD are characterized by outer retinal atrophy, termed geographic atrophy, or neovascularization associated with subretinal and/or intraretinal exudation, termed exudative neovascular AMD. The annual incidence of AMD ranges from 0.3 per 1000 in people who are aged 55 to 59 years to 36.7 per 1000 in people aged 90 years or older. The estimated heritability of late-stage AMD is approximately 71% (95% CI, 18%-88%). Long-term prospective cohort studies show a significantly higher AMD incidence in people who smoke more than 20 cigarettes per day compared with people who never smoked. AMD is diagnosed primarily with clinical examination that includes a special lens that focuses light of the slit lamp through the pupil. Exudative neovascular AMD is best identified using angiography and by optical coherence tomography. Individuals with AMD who take nutritional supplements consisting of high-dose vitamin C, vitamin E, carotenoids, and zinc have a 20% probability to progress to late-stage AMD at 5 years vs a 28% probability for those taking a placebo. In exudative neovascular AMD, 94.6% of patients receiving monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections experience less than a 15-letter visual acuity loss after 12 months compared with 62.2% receiving sham treatment.<br><br>CONCLUSIONS AND RELEVANCE: The prevalence of AMD is anticipated to increase worldwide to 288 million individuals by 2040. Intravitreally administered anti-VEGF treatment is first-line therapy for exudative neovascular AMD.},
}
@article {pmid38192819,
year = {2024},
author = {Li, B and Wang, Z and Zhou, H and Zou, J and Yoshida, S and Zhou, Y},
title = {N6-methyladenosine methylation in ophthalmic diseases: From mechanisms to potential applications.},
journal = {Heliyon},
volume = {10},
number = {1},
pages = {e23668},
pmid = {38192819},
issn = {2405-8440},
abstract = {N6-methyladenosine (m[6]A) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in m[6]A modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that m[6]A modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding m[6]A modification in ophthalmic diseases, changes in m[6]A modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for m[6]A modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.},
}
@article {pmid38192684,
year = {2024},
author = {Wu, Z and Glover, EK and Gee, EE and Hodgson, LAB and Guymer, RH},
title = {Functional Evaluation of Retinal Pigment Epithelium and Outer Retinal Atrophy by High-Density Targeted Microperimetry Testing.},
journal = {Ophthalmology science},
volume = {4},
number = {2},
pages = {100425},
pmid = {38192684},
issn = {2666-9145},
abstract = {PURPOSE: Complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on OCT imaging has recently been proposed to describe end-stage atrophy in age-related macular degeneration (AMD) by international consensus and expected to be associated with a dense scotoma, but such functional evidence is lacking. This study sought to examine the visual sensitivity defects associated with cRORA and to determine OCT features associated with deep defects.<br><br>DESIGN: Observational study.<br><br>PARTICIPANTS: Sixty eyes from 53 participants, including 342 microperimetry tests over 171 study visits.<br><br>METHODS: Participants underwent targeted high-density threshold-based microperimetry testing of atrophic lesions (with at least incomplete RPE and outer retinal atrophy [iRORA]) with a 3.5&#xb0; diameter grid. The maximum extent of signs of atrophy for all lesions was graded on OCT imaging.<br><br>MAIN OUTCOME MEASURES: Number of deep visual sensitivity defects (threshold &#x2264; 10&#xa0;decibels [dB]).<br><br>RESULTS: Presence of choroidal signal hypertransmission &#x2265; 500 &#x3bc;m, complete RPE loss &#x2265;250 &#x3bc;m, and inner nuclear layer and outer plexiform layer subsidence, and hyporeflective wedge-shaped band (defined as nascent geographic atrophy [nGA]) &#x2265; 500 &#x3bc;m (P &#x2264; 0.020), but not RPE attenuation or disruption (P &#x2265; 0.192), were all independently associated with a significant increase in the number of deep visual sensitivity defects &#x2264; 10 dB. Only cRORA lesions with hypertransmission &#x2265; 500 &#x3bc;m or complete RPE loss &#x2265; 250 &#x3bc;m, or with both of these features (P < 0.001), but not lesions with only hypertransmission 250-499 &#x3bc;m (P = 0.303), had significantly more deep visual sensitivity defects &#x2264; 10 dB compared with iRORA lesions. Lesions with nGA &#x2265; 500 &#x3bc;m, irrespective of the presence of hypertransmission &#x2265; 500 &#x3bc;m and/or complete RPE loss &#x2265; 250 &#x3bc;m, also showed a higher number of deep visual sensitivity defects &#x2264; 10 dB compared with lesions without nGA &#x2265; 500 &#x3bc;m (P&#xa0;&#x2264;&#xa0;0.011).<br><br>CONCLUSIONS: Not all cRORA lesions show a difference in the number of deep visual sensitivity defects compared with iRORA. Instead, hypertransmission &#x2265; 500 &#x3bc;m, complete RPE loss &#x2265; 250 &#x3bc;m, and nGA &#x2265; 500 &#x3bc;m are all OCT features independently associated with deep visual sensitivity detects that could help inform the definition of end-stage atrophy on OCT imaging.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38191981,
year = {2024},
author = {Poddar, R and Shukla, V and Alam, Z and Mohan, M},
title = {Automatic segmentation of layers in chorio-retinal complex using Graph-based method for ultra-speed 1.7 MHz wide field swept source FDML optical coherence tomography.},
journal = {Medical &amp; biological engineering &amp; computing},
volume = {62},
number = {5},
pages = {1375-1393},
pmid = {38191981},
issn = {1741-0444},
support = {ICMR-EMR 5/3/8/30/2020-ITR//Indian Council of Medical Research/ ; CRG/2022/001404//Department of Biotechnology, Ministry of Science and Technology, India/ ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retina/diagnostic imaging ; Choroid/diagnostic imaging ; Angiography ; Probability ; },
abstract = {The posterior segment of the human eye complex contains two discrete microstructure and vasculature network systems, namely, the retina and choroid. We present a single segmentation framework technique for segmenting the entire layers present in the chorio-retinal complex of the human eye using optical coherence tomography (OCT) images. This automatic program is based on the graph theory method. This single program is capable of segmenting seven layers of the retina and choroid scleral interface. The graph theory was utilized to find the probability matrix and subsequent boundaries of different layers. The program was also implemented to segment angiographic maps of different chorio-retinal layers using "segmentation matrices." The method was tested and successfully validated on OCT images from six normal human eyes as well as eyes with non-exudative age-related macular degeneration (AMD). The thickness of microstructure and microvasculature for different layers located in the chorio-retinal segment of the eye was also generated and compared. A decent efficiency in terms of processing time, sensitivity, and accuracy was observed compared to the manual segmentation and other existing methods. The proposed method automatically segments whole OCT images of chorio-retinal complex with augmented probability maps generation in OCT volume dataset. We have also evaluated the segmentation results using quantitative metrics such as Dice coefficient and Hausdorff distance This method realizes a mean descent Dice similarity coefficient (DSC) value of 0.82 (range, 0.816-0.864) for RPE and CSI layer.},
}
@article {pmid38190877,
year = {2024},
author = {Mitroo, D and Das, DN and Hamilton, PD and Kumfer, BM and Ravi, N},
title = {Combustion conditions influence toxicity of flame-generated soot to ocular (ARPE-19) cells.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {344},
number = {},
pages = {123307},
doi = {10.1016/j.envpol.2024.123307},
pmid = {38190877},
issn = {1873-6424},
mesh = {*Soot/analysis ; *Oxygen/analysis ; Temperature ; },
abstract = {Soot is a prevalent aerosol found both indoors and outdoors that has several sources, such as natural (e.g., wildfires), civilian (e.g., cooking), or military (e.g., burn pit operation). Additionally, within the sources, factors that influence the physicochemical properties of the soot include combustion temperature, oxygen availability, and fuel type. Being able to reproduce soot in the laboratory and systematically assess its toxicity is important in the pursuit of elucidating pathologies associated with its exposure. Of the organs of interest, we targeted the eye given the scant attention received. Yet, air pollution constituents such as soot have been linked to diseases such as age-related macular degeneration and proliferative vitreoretinopathy. We developed a bench-scale system to synthesize different types of soot, that is, soot with a systematically varied physical attributes or chemical composition. We used common analytical techniques to probe such properties, and used statistical analyses to correlate them with toxicity in vitro using ARPE-19 cells. Within the range of flame conditions studied, we find that soot toxicity increases with increasing oxygen concentration in fuel-rich premixed flames, and weakly increases with decreasing flame temperature. Additionally, soot particles produced in premixed flames are generally smaller in size, exhibit a lesser fractal structure, and are considerably more toxic to ARPE-19 cells than soot particles produced in non-premixed flames.},
}
@article {pmid38189160,
year = {2024},
author = {Tang, Y and Fang, C and Shi, J and Chen, H and Chen, X and Yao, X},
title = {Antioxidant potential of chlorogenic acid in Age-Related eye diseases.},
journal = {Pharmacology research &amp; perspectives},
volume = {12},
number = {1},
pages = {e1162},
pmid = {38189160},
issn = {2052-1707},
support = {2021023//Key Program of Administration of Chinese Medicine of Hunan Province of China/ ; 20A370//Key Project of Educational Commission of Hunan Province of China/ ; 82174443//National Natural Science Foundation of China/ ; 2021JJ30527//Natural Science Foundation of Hunan Province of China/ ; },
mesh = {Humans ; Antioxidants/pharmacology/therapeutic use ; Chlorogenic Acid/pharmacology/therapeutic use ; *Eye Diseases/drug therapy ; Oxidative Stress ; *Diabetic Retinopathy/drug therapy ; },
abstract = {Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue-light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti-inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age-related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research.},
}
@article {pmid38188933,
year = {2023},
author = {Moy, AB and Kamath, A and Ternes, S and Kamath, J},
title = {The Challenges to Advancing Induced Pluripotent Stem Cell-Dependent Cell Replacement Therapy.},
journal = {Medical research archives},
volume = {11},
number = {11},
pages = {},
pmid = {38188933},
issn = {2375-1916},
support = {R44 GM139403/GM/NIGMS NIH HHS/United States ; },
abstract = {Induced pluripotent stem cells (iPSC) represent a potentially exciting regenerative-medicine cell therapy for several chronic conditions such as macular degeneration, soft tissue and orthopedic conditions, cardiopulmonary disease, cancer, neurodegenerative disorders and metabolic disorders. The field of iPSC therapeutics currently exists at an early stage of development. There are several important stakeholders that include academia, industry, regulatory agencies, financial institutions and patients who are committed to advance the field. Yet, unlike more established therapeutic modalities like small and large molecules, iPSC therapies pose significant unique challenges with respect to safety, potency, genetic stability, immunogenicity, tumorgenicity, cell reproducibility, scalability and engraftment. The aim of this review article is to highlight the unique technical challenges that need to be addressed before iPSC technology can be fully realized as a cell replacement therapy. Additionally, this manuscript offers some potential solutions and identifies areas of focus that should be considered in order for the iPSC field to achieve its promise. The scope of this article covers the following areas: (1) the impact of different iPSC reprogramming methods on immunogenicity and tumorigenicity; (2) the effect of genetic instability on cell reproducibility and differentiation; (3) the role of growth factors and post-translational modification on differentiation and cell scalability; (4) the potential use of gene editing in improving iPSC differentiation; (5) the advantages and disadvantages between autologous and allogeneic cell therapy; (6) the regulatory considerations in developing a viable and reproducible cell product; and (7) the impact of local tissue inflammation on cell engraftment and cell viability.},
}
@article {pmid38188607,
year = {2024},
author = {Kuraishi, T and Kawamura, H and Saito, I and Sakurai, T},
title = {Transscleral drainage to treat peripheral exudative hemorrhagic chorioretinopathy caused by retinal pigment epithelial hemorrhage.},
journal = {American journal of ophthalmology case reports},
volume = {33},
number = {},
pages = {101977},
pmid = {38188607},
issn = {2451-9936},
abstract = {PURPOSE: To report a case of peripheral exudative hemorrhagic chorioretinopathy with hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage treated with transscleral subretinal fluid drainage.<br><br>OBSERVATIONS: The patient was a 70-year-old man with a 15-year history of diabetic retinopathy and age-related macular degeneration. During follow-up, he developed a sudden decrease in visual acuity in the left eye. Corrected visual acuity was 20/32 in the right eye and 20/800 in the left eye, and hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage were observed in the left eye. Pars plana vitrectomy and transscleral drainage of the subretinal hemorrhage and subretinal pigment epithelial hemorrhage were performed. We initially attempted to displace the subretinal pigment epithelial hemorrhage, but the subretinal hemorrhage was also displaced via a retinal pigment epithelial tear located in the temporal macula. The retina was completely reattached, although visual acuity in the left eye remained at 20/400.<br><br>CONCLUSIONS AND IMPORTANCE: This report describes a surgical technique for hemorrhagic retinal detachment and subretinal pigment epithelial hemorrhage due to peripheral exudative hemorrhagic chorioretinopathy. We believe that transscleral subretinal fluid drainage without intentional retinal tear is a useful and safe method for patients with extensive hemorrhagic retinal detachment.},
}
@article {pmid38187905,
year = {2024},
author = {Hu, W and Cai, W and Wu, Y and Ren, C and Yu, D and Li, T and Shen, T and Xu, D and Yu, J},
title = {Topical Application of Cell-Penetrating Peptide Modified Anti-VEGF Drug Alleviated Choroidal Neovascularization in Mice.},
journal = {International journal of nanomedicine},
volume = {19},
number = {},
pages = {35-51},
pmid = {38187905},
issn = {1178-2013},
mesh = {Humans ; Animals ; Mice ; *Cell-Penetrating Peptides ; Fluorescein-5-isothiocyanate ; Ranibizumab ; Vascular Endothelial Growth Factor A ; *Choroidal Neovascularization/drug therapy ; Human Umbilical Vein Endothelial Cells ; *Macular Degeneration ; Ophthalmic Solutions ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy.<br><br>METHODS: Two complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments.<br><br>RESULTS: Both 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts.<br><br>CONCLUSION: In this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD.},
}
@article {pmid38187496,
year = {2023},
author = {Nakai, A and Lee, D and Shoda, C and Negishi, K and Nakashizuka, H and Yamagami, S and Kurihara, T},
title = {Modulation of Hypoxia-Inducible Factors and Vascular Endothelial Growth Factor Expressions by Superfood Camu-Camu (Myrciaria dubia) Treatment in ARPE-19 and Fetal Human RPE Cells.},
journal = {Journal of ophthalmology},
volume = {2023},
number = {},
pages = {6617981},
pmid = {38187496},
issn = {2090-004X},
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy via intravitreal injection is an effective treatment for patients with abnormal ocular neovascularization, such as age-related macular degeneration (AMD) and diabetic macular edema (DME). However, prolonged and frequent anti-VEGF treatment is associated with a risk of local and systemic adverse events, including geographic atrophy, cerebrovascular disease, and death. Furthermore, some patients do not adequately respond to anti-VEGF therapy. Hypoxia-inducible factor (HIF) is a transcription factor that controls the expression of hypoxia-responsive genes involved in angiogenesis, inflammation, and metabolism. The HIF/VEGF pathway plays an important role in neovascularization, and the inhibition of HIF activation could be an effective biomolecular target for neovascular diseases. The demand for disease prevention or treatment using functional foods such as superfoods has increased in recent years. Few reports to date have focused on the antineovascular effects of superfoods in the retinal pigment epithelium (RPE). In light of the growing demand for functional foods, we aimed to find novel HIF inhibitors from superfoods worked in RPE cells, which could be an adjuvant for anti-VEGF therapy.<br><br>METHODS: Seven superfoods were examined to identify novel HIF inhibitor candidates using luciferase assay screening. We used the human RPE cell line ARPE-19 and fetal human RPE (fhRPE) to investigate the biomolecular actions of novel HIF inhibitors using quantitative PCR and western blotting.<br><br>RESULTS: Under CoCl2-induced pseudohypoxic condition and 1% oxygen hypoxic incubation, camu-camu (Myrciaria dubia) showed HIF inhibitory effects determined by luciferase assays. Camu-camu downregulated HIF-1&#x3b1; and VEGFA mRNA expressions in a concentration-dependent manner. Camu-camu also inhibited HIF-1&#x3b1; protein expressions, and its inhibitory effect was greater than that of vitamin C, which is present at high levels in camu-camu.<br><br>CONCLUSION: The camu-camu extract suppressed the activation of HIF and VEGF in RPE cells. This could assist anti-VEGF therapy in patients with abnormal ocular neovascularization.},
}
@article {pmid38187126,
year = {2024},
author = {Wykoff, CC and Garmo, V and Tabano, D and Menezes, A and Kim, E and Fevrier, HB and LaPrise, A and Leng, T},
title = {Impact of Anti-VEGF Treatment and Patient Characteristics on Vision Outcomes in Neovascular Age-related Macular Degeneration: Up to 6-Year Analysis of the AAO IRIS® Registry.},
journal = {Ophthalmology science},
volume = {4},
number = {2},
pages = {100421},
pmid = {38187126},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate anti-VEGF treatment patterns and the influence of patient demographic and clinical characteristics on up to 6-year vision outcomes in neovascular age-related macular degeneration.<br><br>DESIGN: Retrospective, multicenter, noninterventional registry study with up to 6 years of follow-up.<br><br>PARTICIPANTS: A cohort of 254 655 eyes (226 767 patients) with first anti-VEGF injection and at least 2 years of follow-up; 160 423 eyes had visual acuity (VA) data.<br><br>METHODS: Anonymized patient data were collected in the United States through the IRIS&#xae; Registry (Intelligent Research in Sight).<br><br>MAIN OUTCOME MEASURES: Changes in VA from baseline; frequency of and gaps between intravitreal anti-VEGF injections; treatment discontinuations; switching anti-VEGF agents; and influence of baseline clinical and demographic characteristics on VA.<br><br>RESULTS: After a mean VA increase of 3.0 ETDRS letters at year 1, annual decreases led to a net loss from baseline of 4.6 letters after 6 years. Patients with longer follow-ups had better baseline and follow-up VA. From a mean of 7.2 in year 1 and 5.6 in year 2, mean injections plateaued between 4.2 to 4.6 in years 3 through 6. Treatment was discontinued in 38.8% of eyes and switched in 32.3%. When adjusting for differences at baseline, every additional injection resulted in a 0.68 letter improvement from baseline to year 1; thus, multiple injections in a year have the potential to be clinically meaningful. Older age, male gender, Medicaid insurance, and not being treated by a retina specialist were associated with a higher likelihood of vision loss at year 1. Of the patients, 58.5% lost &#x2265; 10 letters VA at least once during follow-up, with 14.5% of patients experiencing sustained poor vision after a median of 3.4 years.<br><br>CONCLUSIONS: After modest mean VA improvement with intravitreal anti-VEGF injections at year 1, patients netted a loss of VA by year 6. Injection frequency decreased over time, and this was paired with a relatively high rate of discontinuation. Modeling suggested that more frequent injections were associated with better VA. Difficulty with continuous adherence to frequent intravitreal injections may have contributed to undertreatment resulting in less-than-optimal vision outcomes.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38186747,
year = {2023},
author = {Anderson, DMG and Kotnala, A and Migas, LG and Patterson, NH and Tideman, L and Cao, D and Adhikari, B and Messinger, JD and Ach, T and Tortorella, S and Van de Plas, R and Curcio, CA and Schey, KL},
title = {Lysolipids are prominent in subretinal drusenoid deposits, a high-risk phenotype in age-related macular degeneration.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {},
pmid = {38186747},
issn = {2674-0826},
support = {P30 DK020593/DK/NIDDK NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; U54 DK134302/DK/NIDDK NIH HHS/United States ; U54 EY032442/EY/NEI NIH HHS/United States ; },
abstract = {INTRODUCTION: Age related macular degeneration (AMD) causes legal blindness worldwide, with few therapeutic targets in early disease and no treatments for 80% of cases. Extracellular deposits, including drusen and subretinal drusenoid deposits (SDD; also called reticular pseudodrusen), disrupt cone and rod photoreceptor functions and strongly confer risk for advanced disease. Due to the differential cholesterol composition of drusen and SDD, lipid transfer and cycling between photoreceptors and support cells are candidate dysregulated pathways leading to deposit formation. The current study explores this hypothesis through a comprehensive lipid compositional analysis of SDD.<br><br>METHODS: Histology and transmission electron microscopy were used to characterize the morphology of SDD. Highly sensitive tools of imaging mass spectrometry (IMS) and nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) in positive and negative ion modes were used to spatially map and identify SDD lipids, respectively. An interpretable supervised machine learning approach was utilized to compare the lipid composition of SDD to regions of uninvolved retina across 1873 IMS features and to automatically discern candidate markers for SDD. Immunohistochemistry (IHC) was used to localize secretory phospholipase A2 group 5 (PLA2G5).<br><br>RESULTS: Among the 1873 detected features in IMS data, three lipid classes, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lysophosphatidic acid (LysoPA) were observed nearly exclusively in SDD while presumed precursors, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidic acid (PA) lipids were detected in SDD and adjacent photoreceptor outer segments. Molecular signals specific to SDD were found in central retina and elsewhere. IHC results indicated abundant PLA2G5 in photoreceptors and retinal pigment epithelium (RPE).<br><br>DISCUSSION: The abundance of lysolipids in SDD implicates lipid remodeling or degradation in deposit formation, consistent with ultrastructural evidence of electron dense lipid-containing structures distinct from photoreceptor outer segment disks and immunolocalization of secretory PLA2G5 in photoreceptors and RPE. Further studies are required to understand the role of lipid signals observed in and around SDD.},
}
@article {pmid38185453,
year = {2024},
author = {Boudousq, C and Nguyen, V and Hunt, A and Gillies, M and Zarranz-Ventura, J and O'Toole, L and Mangelschots, E and Kusenda, P and Schmidt-Erfurdt, U and Pollreisz, A and Kheir, WJ and Arruabarrena, C and Vujosevic, S and Barthelmes, D and Creuzot-Garcher, C and Gabrielle, PH},
title = {European Unmet Needs in the Management of Neovascular Age-Related Macular Degeneration in Daily Practice: Data from the Fight Retinal Blindness! Registry.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {6},
pages = {527-536},
doi = {10.1016/j.oret.2024.01.004},
pmid = {38185453},
issn = {2468-6530},
mesh = {Humans ; Male ; Female ; *Registries ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Intravitreal Injections ; Retrospective Studies ; Aged ; *Visual Acuity ; *Tomography, Optical Coherence/methods ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Europe/epidemiology ; *Wet Macular Degeneration/drug therapy/diagnosis ; Follow-Up Studies ; Ranibizumab/administration &amp; dosage ; Aged, 80 and over ; Bevacizumab/administration &amp; dosage ; Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors/administration &amp; dosage ; Blindness/etiology/prevention &amp; control/epidemiology ; Treatment Outcome ; },
abstract = {PURPOSE: To evaluate the proportion, predictors, and outcomes of patients with neovascular age-related macular degeneration (nAMD) treated with a high burden of VEGF inhibitor intravitreal (IVT) injections after 2 years in routine clinical practice.<br><br>DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project, of patients treated in European centers.<br><br>PARTICIPANTS: Treatment-na&#xef;ve eyes (1 eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed the following 3 treatment-burden groups defined by the mean interval of the 3 closest injections to the 24-month visit: (1) those with a high-treatment burden had injection intervals &#x2264; 42 days, (2) those with a low-treatment burden had injection intervals between 43 and 83 days; and (3)&#xa0;those with tolerable treatment burden had injection intervals between 84 and 365 days.<br><br>METHODS: Multinomial regression was used to evaluate baseline risk predictors of patients requiring a high-treatment burden.<br><br>MAIN OUTCOME MEASURES: The proportion of patients that experienced a high-treatment burden at 2 years and its predictors.<br><br>RESULTS: We identified 2038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (quartile 1, quartile 3) of 13 (10, 17) injections. The proportion of patients with a high-treatment burden was 25% (516 patients) at 2 years. Younger patients (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96-0.99; P < 0.01) were more likely to have high-treatment burden, whereas eyes with type 3 choroidal neovascular lesions at baseline were significantly less likely (OR, 0.26; 95% CI, 0.13-0.52; P < 0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95% CI, 1.34-11.01; P&#xa0;= 0.01) and persistent active intraretinal (OR, 1.56; 95% CI, 1.18-2.06; P < 0.01) or subretinal fluid only (OR, 2.21; 95% CI, 1.52-3.21; P < 0.01) after the loading phase had a higher risk of high treatment burden at 2 years.<br><br>CONCLUSIONS: High treatment burden is a common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40% discontinuing treatment within 2 years.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38185342,
year = {2024},
author = {Gopinath, T and Shin, K and Tian, Y and Im, W and Struppe, J and Perrone, B and Hassan, A and Marassi, FM},
title = {Solid-state NMR MAS CryoProbe enables structural studies of human blood protein vitronectin bound to hydroxyapatite.},
journal = {Journal of structural biology},
volume = {216},
number = {1},
pages = {108061},
pmid = {38185342},
issn = {1095-8657},
support = {P01 AG081167/AG/NIA NIH HHS/United States ; R35 GM118186/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Vitronectin ; *Durapatite ; Magnetic Resonance Spectroscopy/methods ; Magnetic Resonance Imaging ; Nuclear Magnetic Resonance, Biomolecular/methods ; },
abstract = {The low sensitivity of nuclear magnetic resonance (NMR) is a major bottleneck for studying biomolecular structures of complex biomolecular assemblies. Cryogenically cooled probe technology overcomes the sensitivity limitations enabling NMR applications to challenging biomolecular systems. Here we describe solid-state NMR studies of the human blood protein vitronectin (Vn) bound to hydroxyapatite (HAP), the mineralized form of calcium phosphate, using a CryoProbe designed for magic angle spinning (MAS) experiments. Vn is a major blood protein that regulates many different physiological and pathological processes. The high sensitivity of the CryoProbe enabled us to acquire three-dimensional solid-state NMR spectra for sequential assignment and characterization of site-specific water-protein interactions that provide initial insights into the organization of the Vn-HAP complex. Vn associates with HAP in various pathological settings, including macular degeneration eyes and Alzheimer's disease brains. The ability to probe these assemblies at atomic detail paves the way for understanding their formation.},
}
@article {pmid38184882,
year = {2024},
author = {Mahmoud, SS and Morsy, SA and Ahmed, RT and Aly, EM},
title = {The impact of photoreceptor layer loss on different ocular tissues: Insights from FTIR spectroscopy.},
journal = {Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy},
volume = {309},
number = {},
pages = {123827},
doi = {10.1016/j.saa.2023.123827},
pmid = {38184882},
issn = {1873-3557},
mesh = {Spectroscopy, Fourier Transform Infrared/methods ; *Proteins ; *Lens, Crystalline ; },
abstract = {Photoreceptor loss has significant consequences for visual function, and its management is a critical component for treating not only retinal diseases such as age-related macular degeneration and retinitis pigmentosa but also its ocular consequences. On the other hand, Fourier transform infrared spectroscopy is an excellent tool to investigate molecular structure and dynamics of biological samples, and as a non-destructive and label free measurement, it does not perturb the samples. In this study, detailed analyses of the recorded FTIR spectra from cornea, lens and sclera were performed to monitor the distribution of ocular abnormalities due to photoreceptor layer loss after 1, 3 and 6 days. FTIR data were statistically evaluated by multivariate analysis and Bonferroni means comparison. The obtained results revealed that ocular abnormalities associated with photoreceptor layer loss are varied among the investigated tissues, and comprise changes in both hydrogen bond network around proteins and lipid disorder. Structural modifications of protein secondary structure were reported in all investigated tissues. Clinically, the concluded information from FTIR data and its statistical evaluation can contribute to the development of therapeutic strategies for these heterogeneous changes.},
}
@article {pmid38183849,
year = {2024},
author = {Lazzara, F and Conti, F and Giuffrida, E and Eandi, CM and Drago, F and Platania, CBM and Bucolo, C},
title = {Integrating network pharmacology: The next-generation approach in ocular drug discovery.},
journal = {Current opinion in pharmacology},
volume = {74},
number = {},
pages = {102425},
doi = {10.1016/j.coph.2023.102425},
pmid = {38183849},
issn = {1471-4973},
mesh = {Humans ; Network Pharmacology ; Eye ; *Diabetic Retinopathy/drug therapy ; *Retinal Diseases ; Drug Discovery ; },
abstract = {With the spread of the "omics" sciences, the approaches of systems biology can be considered as new paradigms of pharmacological research for discovery of novel targets and/or treatments for complex multifactorial diseases. Data from omics sciences can be used for the design of biologic networks, that in turn can be quantitatively analyzed to identify new pharmacological targets. In this review, we will introduce the concept of network pharmacology, particularly the application of this innovative approach in the field of ocular pharmacology, with a focus on retinal diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma.},
}
@article {pmid38183525,
year = {2024},
author = {Kodjikian, L and Arias Barquet, L and Papp, A and Kertes, PJ and Midena, E and Ernest, J and Silva, R and Schmelter, T and Niesen, T and Leal, S},
title = {Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.},
journal = {Advances in therapy},
volume = {41},
number = {3},
pages = {1010-1024},
pmid = {38183525},
issn = {1865-8652},
mesh = {Humans ; Middle Aged ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use ; Treatment Outcome ; Visual Acuity ; Aged ; },
abstract = {INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&amp;E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year.<br><br>METHODS: Patients were aged&#x2009;&#x2265;&#x2009;51&#xa0;years and had completed&#x2009;&#x2265;&#x2009;1&#xa0;year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [-&#x2009;1 or +&#x2009;2&#xa0;weeks] for 3&#xa0;months followed by IVT-AFL every 2&#xa0;months [6-12&#xa0;weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2&#xa0;mg in either a T&amp;E (minimum treatment interval of 8&#xa0;weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n&#x2009;=&#x2009;168), or a fixed dosing regimen (treatment every 8&#xa0;weeks [&#xb1;&#x2009;3&#xa0;days]; n&#x2009;=&#x2009;168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (<&#x2009;15-letter loss) at W52.<br><br>RESULTS: The full analysis set comprised 332 patients (T&amp;E: n&#x2009;=&#x2009;165; fixed dosing: n&#x2009;=&#x2009;167). Mean BCVA change (baseline to W52) was&#x2009;-&#x2009;0.3&#x2009;&#xb1;&#x2009;7.5 vs. -&#x2009;0.5&#x2009;&#xb1;&#x2009;8.4 letters (T&amp;E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [-&#x2009;1.51 to 1.96] letters; P&#x2009;<&#x2009;0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&amp;E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was&#x2009;-&#x2009;24&#x2009;&#xb1;&#x2009;55 (T&amp;E) and&#x2009;-&#x2009;33&#x2009;&#xb1;&#x2009;47 (fixed dosing) &#xb5;m. Last treatment interval to W76 was&#x2009;&#x2265;&#x2009;12&#xa0;weeks for 37.0% of T&amp;E patients. No new safety signals were identified.<br><br>CONCLUSION: IVT-AFL T&amp;E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52&#xa0;weeks in patients with nAMD who have completed&#x2009;&#x2265;&#x2009;1&#xa0;year of treatment, while reducing treatment burden.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.},
}
@article {pmid38181813,
year = {2024},
author = {Gunnemann, ML and Ziegler, M and Book, M and Gunnemann, F and Rothaus, K and Spital, G and Gutfleisch, M and Lange, C and Lommatzsch, AP and Pauleikhoff, D},
title = {Is Exudative Neovascular AMD a Chronic Disease? Analysis of Long-term Progression under Anti-VEGF Therapy.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {241},
number = {12},
pages = {1335-1340},
doi = {10.1055/a-2239-6394},
pmid = {38181813},
issn = {1439-3999},
mesh = {Humans ; Female ; Male ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage ; Chronic Disease ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Disease Progression ; Aged, 80 and over ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor ; Bevacizumab/therapeutic use ; Wet Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; Visual Acuity/drug effects ; Follow-Up Studies ; Treatment Outcome ; Choroidal Neovascularization/drug therapy ; },
abstract = {BACKGROUND: Anti-VEGF therapy is the standard treatment for exudative neovascular age-related macular degeneration (nAMD) caused by the development of macular neovascularisation (MNV) with associated fluid exudation. The therapeutic strategies (T&amp;E or PRN) assumed a scarring transformation of the MNV and exit strategies and were formulated accordingly. The present study investigates this hypothesis as a real-life long-term analysis.<br><br>PATIENTS: 150 eyes of 97 patients were continuously followed up over a mean period of 5.1 years (1&#x200a;-&#x200a;14 years) after initiation of anti-VEGF therapy between 2009&#x200a;-&#x200a;2017 until 2022. Treatment was based on the PRN regimen analogous to the IVAN study with ranibizumab, aflibercept or bevacizumab. The length and intensity of therapy were evaluated.<br><br>RESULTS: Of these 150 eyes, 119 (79.3%) required ongoing anti-VEGF therapy, while in 18 eyes (12.0%) therapy could be discontinued due to stabilisation of the situation. In 13 eyes (8.7%), therapy was discontinued due to deterioration in visual acuity to <&#x2009;0.05. With ongoing therapy, therapy was often protracted, with an indication for therapy at the last documented doctor's visit, while stabilisation was often achieved within the first 2 years of treatment. The treatment intensity increased to 7.7&#x200a;-&#x200a;8.0 injections/year, especially after 2013, with the introduction of OCT-based treatment criteria. Most eyes (74.8%) with ongoing therapy required 6&#x200a;-&#x200a;9 injections/year even in the last three years of treatment.<br><br>CONCLUSION: The fact that in the present study there is a long-term and intensive need for therapy in the majority of patients (approx. 80%) with exudative nAMD, supports the assessment that nAMD should be regarded as a chronic disease. Therefore, a proactive treatment strategy with consistent therapy at any sign of lesion activity might be recommended. Particularly in view of the risk of irreversible loss of vision, long term adherence of patients is also crucial for the best possible long term therapeutic outcome.},
}
@article {pmid38180789,
year = {2024},
author = {Adelman, M and Weber, I},
title = {Reflecting on Decades of Data: The Global Burden of Disease-Cochrane Project.},
journal = {JMIR dermatology},
volume = {7},
number = {},
pages = {e41323},
pmid = {38180789},
issn = {2562-0959},
}
@article {pmid38180772,
year = {2024},
author = {Wu, K and Wu, J and Yao, J and Song, R and Jing, R and Li, W and Wang, X and Wang, N and Zheng, Y and Yao, L},
title = {Age-Related Macular Degeneration Choroidal Vascular Distribution Characteristics Based on Indocyanine Green Angiography.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {1},
pages = {16},
pmid = {38180772},
issn = {1552-5783},
mesh = {Humans ; *Indocyanine Green ; Retrospective Studies ; Angiography ; *Macular Degeneration/diagnosis ; Choroid ; },
abstract = {PURPOSE: The purpose of this study was to present our findings of the distribution pattern of choroidal arteries and large veins in patients with age-related macular degeneration (AMD) using indocyanine green angiography (ICGA).<br><br>METHODS: A retrospective analysis was conducted on 980 patients who underwent ICGA at The Second Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2023, including 240 patients with AMD. Secondary image processing was applied to the angiographic videos to obtain posterior distribution maps of choroidal arteries and large veins. Differences between different distribution patterns regarding age, gender, eye laterality, and circulation time were compared. We also conducted a comparison of choroidal vascular distribution characteristics between patients with AMD and patients with diabetic retinopathy (DR) and provided a summary of choroidal vascular distribution patterns in AMD.<br><br>RESULTS: The filling patterns of choroidal arteries can be classified into the invisible trunk arteries type, the partially masked trunk arteries type, and the exposed trunk arteries type. The vascular topography of the large choroidal vein can be classified into the watershed type, the non-watershed type, and the unknown type, further divided into six subtypes. The distribution patterns of choroidal arteries and veins were significantly correlated with age (P < 0.001). Left eye, older age, and the exposed trunk arteries type were independent risk factors for non-watershed large choroidal vein (P < 0.05). The non-watershed type was the main characteristic of the venous phase in AMD.<br><br>CONCLUSIONS: The distribution characteristics of the arterial and venous patterns in AMD suggest atrophy of the small blood vessels in the choroid and insufficient perfusion pressure of the blood flow.},
}
@article {pmid38180632,
year = {2024},
author = {Tombolini, B and Crincoli, E and Sacconi, R and Battista, M and Fantaguzzi, F and Servillo, A and Bandello, F and Querques, G},
title = {Optical Coherence Tomography Angiography: A 2023 Focused Update on Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {2},
pages = {449-467},
pmid = {38180632},
issn = {2193-8245},
abstract = {Optical coherence tomography angiography (OCTA) has extensively enhanced our comprehension of eye microcirculation and of its associated diseases. In this narrative review, we explored the key concepts behind OCTA, as well as the most recent evidence in the pathophysiology of age-related macular degeneration (AMD) made possible by OCTA. These recommendations were updated since the publication in 2020, and are targeted for 2023. Importantly, as a future perspective in OCTA technology, we will discuss how artificial intelligence has been applied to OCTA, with a particular emphasis on its application to AMD study.},
}
@article {pmid38176443,
year = {2024},
author = {Wang, J and Wang, Z and Liu, J and Zhou, M and Wang, H and Zhu, H and Jiang, M and Bo, Q and Sun, X},
title = {Chrysin alleviates DNA damage to improve disturbed immune homeostasis and pro-angiogenic environment in laser-induced choroidal neovascularization.},
journal = {Biochimica et biophysica acta. Molecular cell research},
volume = {1871},
number = {3},
pages = {119657},
doi = {10.1016/j.bbamcr.2023.119657},
pmid = {38176443},
issn = {1879-2596},
mesh = {Humans ; *Retinal Pigment Epithelium ; Vascular Endothelial Growth Factor A/genetics ; *Choroidal Neovascularization/etiology/genetics ; DNA Damage ; Lasers ; *Flavonoids ; },
abstract = {Choroidal neovascularization (CNV) is a devastating pathology of numerous ocular diseases, such as wet age-related macular degeneration (wAMD), which causes irreversible vision loss. Although anti-vascular endothelial growth factor (VEGF) therapy has been widely used, poor response or no response still exists in some cases, suggesting that there are other components involved in the angiogenic process. Therefore, the underlying mechanism needs to be clarified and new target of anti-angiogenic therapy is urgently needed. It has been demonstrated that damaged retinal pigment epithelium (RPE) cells can activate inflammasome, driving a degenerative tissue environment and an enhanced pro-angiogenic response, which implies that RPE dysfunction may be a hallmark of the pathogenesis. Previously, we have shown that DNA damage can induce RPE dysfunction, triggering senescence-associated secretory phenotype (SASP) and local inflammation. In this study, we identify that chrysin can reduce DNA damage, especially telomere erosion in vitro, thus compromise the dysfunction of RPE and the decreased expression of SASP factor. Importantly, we find that DNA damage of RPE cells is remarkable in laser-induced CNV lesion, resulting in inflammatory response, which can be ameliorated by chrysin, mainly through IL-17 signaling pathway and its downstream signal transducer and activator of transcription 3 (STAT3) activities. In summary, our results indicate the interplay between DNA damage, perturbed RPE homeostasis, inflammatory response and angiogenesis in laser-induced CNV, and more importantly, chrysin may be an effective therapeutic supplement for CNV.},
}
@article {pmid38175639,
year = {2024},
author = {Liu, YS and Pan, JQ and Pan, XB and Kong, FS and Zhang, JQ and Wei, ZY and Xu, ZH and Rao, JH and Wang, JH and Chen, JH},
title = {Comparative Analysis of Molecular Landscape in Mouse Models and Patients Reveals Conserved Inflammation Pathways in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {1},
pages = {13},
pmid = {38175639},
issn = {1552-5783},
mesh = {Humans ; Animals ; Mice ; Proteomics ; *Macular Degeneration/genetics ; Retina ; Inflammation ; *Retinal Degeneration ; *Choroidal Neovascularization/genetics ; Disease Models, Animal ; },
abstract = {PURPOSE: The purpose of this study was to identify key genes and their regulatory networks that are conserved in mouse models of age-related macular degeneration (AMD) and human AMD.<br><br>METHODS: Retinal RNA-Seq was performed in laser-induced choroidal neovascularization (CNV) mice at day 3 and day 7 after photocoagulation. Mass spectrometry-based proteomic analysis was performed with retinas collected at day 3. Retinal RNA-Seq data was further compared among mouse models of laser-induced CNV and NaIO3-induced retinal degeneration (RD) and a large AMD cohort.<br><br>RESULTS: Retinal RNA-Seq revealed upregulated genes and pathways related to innate immunity and inflammation in mice with CNV, with more profound changes at the early stage (day 3). Proteomic analysis further validated these differentially expressed genes and their networks in retinal inflammation during CNV. Notably, the most evident overlap in the retina of mice with laser-induced CNV and NaIO3-induced RD was the upregulation of inflammation-related genes, pointing to a common vital role of retinal inflammation in the early stage for both mouse AMD models. Further comparative transcriptomic analysis of the mouse AMD models and human AMD identified 48 conserved genes mainly involved in inflammation response. Among them, B2M, C3, and SERPING1 were upregulated in all stages of human AMD and the mouse AMD models compared to controls.<br><br>CONCLUSIONS: Our study demonstrates conserved molecular changes related to retinal inflammation in mouse AMD models and human AMD and provides new insight into the translational application of these mouse models in studying AMD mechanisms and treatments.},
}
@article {pmid38175625,
year = {2024},
author = {Sutton, SS and Magagnoli, J and Cummings, TH and Hardin, JW and Ambati, J},
title = {Alzheimer Disease Treatment With Acetylcholinesterase Inhibitors and Incident Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {142},
number = {2},
pages = {108-114},
pmid = {38175625},
issn = {2168-6173},
mesh = {Humans ; Male ; Female ; Aged ; *Alzheimer Disease/diagnosis/drug therapy/epidemiology ; Cholinesterase Inhibitors/therapeutic use ; Acetylcholinesterase/therapeutic use ; Retrospective Studies ; *Macular Degeneration/diagnosis/drug therapy/epidemiology ; },
abstract = {IMPORTANCE: Age-related macular degeneration (AMD) is a serious and common ophthalmologic disorder that is hypothesized to result, in part, from inflammatory reactions in the macula. Alzheimer disease (AD) treatment, acetylcholinesterase inhibitors (AChEIs), have anti-inflammatory effects and it remains unclear if they modify the risk of AMD.<br><br>OBJECTIVE: To investigate the association between AChEI medications and the incidence of AMD.<br><br>This propensity score-matched retrospective cohort study took place at health care facilities within the US Department of Veterans Affairs (VA) health care system from January 2000 through September 2023. Participants included patients diagnosed with AD between ages 55 and 80 years with no preexisting diagnosis of AMD in the VA database.<br><br>EXPOSURE: AChEIs prescription dispensed as pharmacologic treatments for AD.<br><br>MAIN OUTCOMES AND MEASURE: The first diagnosis of AMD.<br><br>RESULTS: A total of 21&#x202f;823 veterans with AD (mean [SD] age, 72.3 [6.1] years; 21&#x202f;313 male participants [97.7%] and 510 female participants [2.3%]) were included. Propensity score-matched Cox model reveals each additional year of AChEI treatment was associated with a 6% lower hazard of AMD (hazard ratio, 0.94; 95% CI, (0.89-0.99).<br><br>CONCLUSIONS AND RELEVANCE: This observational study reports a small reduction in the risk of AMD among veterans with AD receiving AChEIs. Randomized clinical trials would be needed to determine if there is a cause-and-effect relationship and further research is required to validate these findings across diverse populations.},
}
@article {pmid38172608,
year = {2024},
author = {Stang, A and Schmidt, B and Schramm, S and Kowall, B and Jöckel, KH and Erbel, R and Kuss, O and Geerling, G},
title = {Synergism between coexisting eye diseases and sex in increasing the prevalence of the dry eye syndrome.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {314},
pmid = {38172608},
issn = {2045-2322},
mesh = {Male ; Humans ; Female ; Prevalence ; *Dry Eye Syndromes/epidemiology/diagnosis ; *Glaucoma ; *Cataract ; Surveys and Questionnaires ; *Macular Degeneration/epidemiology ; },
abstract = {The aim was to investigate prevalence of dry eye syndrome (DES) in a population-based sample in Germany. The association between coexisting eye diseases and DES was also of interest. We recontacted participants of the Heinz Nixdorf Recall study between 2018 and 2021 by postal questionnaire that included the Women's Health Study questionnaire on DES. We estimated prevalence of DES and examined DES-associated factors among 2095 participants aged 62-91 years. We performed interaction analyses between sex and coexisting eye diseases in relation to the DES prevalence and performed bias analyses to examine the robustness of the results. The DES prevalence was 31.5% (34-36% after correction for potential non-response bias, 24.1% after correction for outcome misclassification) and it was almost 2.1-times higher in women than in men (women 42.3%, men 20.4%). Among DES subjects, 70.3% had received treatment in the previous 12 months. There was synergism between female sex and coexisting eye diseases (cataract, glaucoma, macular degeneration) in terms of DES prevalence. The extrapolated numbers of patients aged 62-91 years with DES in Germany are 1.1-1.3 million men and 6.1-6.8 million women. The observed synergism may be explained by differences in ocular physiology, subjective perception and response behavior. Women with eye diseases (cataract, glaucoma, macula degeneration) appear to have a markedly higher susceptibility to suffer from DES than men, so that a diagnostic workup of DES symptoms is particularly justified in women with these eye diseases.},
}
@article {pmid38171416,
year = {2024},
author = {Gale, RP and Airody, A and Sivaprasad, S and Hanson, RLW and Allgar, V and McKibbin, M and Morland, AB and Peto, T and Porteous, M and Chakravarthy, U and , },
title = {Improved Structure and Function in Early-Detected Second-Eye Neovascular Age-Related Macular Degeneration: FASBAT/Early Detection of Neovascular Age-Related Macular Degeneration Report 1.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {6},
pages = {545-552},
doi = {10.1016/j.oret.2023.12.012},
pmid = {38171416},
issn = {2468-6530},
mesh = {Humans ; Prospective Studies ; Male ; Female ; *Visual Acuity ; Aged ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/drug therapy/physiopathology ; *Early Diagnosis ; *Fluorescein Angiography/methods ; Follow-Up Studies ; *Quality of Life ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage ; Fundus Oculi ; Intravitreal Injections ; Macula Lutea/pathology/diagnostic imaging ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Aged, 80 and over ; },
abstract = {PURPOSE: Visual acuity (VA) and structural biomarker assessment before and 24-months after early detection and routine treatment of second-eye involvement with neovascular age-related macular degeneration (nAMD) and additional comparison with the first eye affected.<br><br>DESIGN: Prospective, 22-center observational study of participants with unilateral nAMD in the Early Detection of Neovascular AMD (EDNA) study, coenrolled into the Observing Fibrosis, Macular Atrophy and Subretinal Highly Reflective Material, Before and After Intervention with anti-VEGF Treatment (FASBAT) study for an additional 2-year follow-up.<br><br>PARTICIPANTS: Older adults (> 50 years) with new onset nAMD in the first eye.<br><br>METHODS: Assessment of both eyes with OCT, color fundus photography (CFP), clinic-measured VA, and quality of life (QoL).<br><br>MAIN OUTCOME MEASURES: Prevalence of atrophy, subretinal hyperreflective material (SHRM), intraretinal fluid (IRF), subretinal fluid (SRF), and changes in VA over the study duration in both the first and second eyes affected with nAMD. Composite QoL scores over time.<br><br>RESULTS: Of 431 participants recruited to the FASBAT study, the second eye converted to nAMD in 100 participants at a mean of 18.9 months. Visual acuity was 18 letters better at the time of early diagnosis in the second eye compared with conventional diagnosis in the first eye (72.9 vs. 55.6 letters). Visual acuity remained better in the second eye 24.9 months postconversion, at 69.5 letters compared with 59.7 letters at a similar matched time point in the first eye (18.9 months). A greater proportion of participants had vision > 70 letters in the second eye versus the first eye, 24.9 months postconversion (61 vs. 35). Prevalence of SHRM and IRF was lower in the second eye compared with the first eye 24.9 months postconversion. However, SRF prevalence was greater in the second eye 24.9 months postconversion. The development and progression of total area of atrophy appears similar in both eyes. Mean composite QoL scores increased over time, with a significant correlation between VA for the second eye only 24.9 months postconversion.<br><br>CONCLUSION: This study has shown that early detection of exudative AMD in the second eye is associated with reduced prevalence of SHRM and IRF and greater VA, which is significantly correlated with maintained QoL.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38170540,
year = {2024},
author = {Bourauel, L and Vaisband, M and von der Emde, L and Bermond, K and Tarau, IS and Heintzmann, R and Holz, FG and Curcio, CA and Hasenauer, J and Ach, T},
title = {Spectral Analysis of Human Retinal Pigment Epithelium Cells in Healthy and AMD Eyes.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {1},
pages = {10},
pmid = {38170540},
issn = {1552-5783},
support = {R01 EY027948/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/diagnosis/metabolism ; Bruch Membrane/metabolism ; *Geographic Atrophy/metabolism ; *Macula Lutea/metabolism ; },
abstract = {PURPOSE: Retinal pigment epithelium (RPE) cells show strong autofluorescence (AF). Here, we characterize the AF spectra of individual RPE cells in healthy eyes and those affected by age-related macular degeneration (AMD) and investigate associations between AF spectral response and the number of intracellular AF granules per cell.<br><br>METHODS: RPE-Bruch's membrane flatmounts of 22 human donor eyes, including seven AMD-affected eyes (early AMD, three; geographic atrophy, one; neovascular, three) and 15 unaffected macula (<51&#xa0;years, eight; >80&#xa0;years, seven), were imaged at the fovea, perifovea, and near-periphery using confocal AF microscopy (excitation 488&#xa0;nm), and emission spectra were recorded (500-710&#xa0;nm). RPE cells were manually segmented with computer assistance and stratified by disease status, and emission spectra were analyzed using cubic spline transforms. Intracellular granules were manually counted and classified. Linear mixed models were used to investigate associations between spectra and the number of intracellular granules.<br><br>RESULTS: Spectra of 5549 RPE cells were recorded. The spectra of RPE cells in healthy eyes showed similar emission curves that peaked at 580&#xa0;nm for fovea and perifovea and at 575 and 580&#xa0;nm for near-periphery. RPE spectral curves in AMD eyes differed significantly, being blue shifted by 10&#xa0;nm toward shorter wavelengths. No significant association coefficients were found between wavelengths and granule counts.<br><br>CONCLUSIONS: This large series of RPE cell emission spectra at precisely predefined retinal locations showed a hypsochromic spectral shift in AMD. Combining different microscopy techniques, our work has identified cellular RPE spectral AF and subcellular granule properties that will inform future in vivo investigations using single-cell imaging.},
}
@article {pmid38170536,
year = {2024},
author = {Hashimoto, Y and Inoda, S and Takahashi, H and Takahashi, R and Yoshida, H and Fujino, Y and Sakamoto, S and Kawashima, H and Yanagi, Y},
title = {Factors Associated With Intraocular Inflammation in Neovascular Age-Related Macular Degeneration Patients Treated With Brolucizumab.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {1},
pages = {8},
pmid = {38170536},
issn = {1552-5783},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Cytokines ; Inflammation/drug therapy ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Matrix Metalloproteinase 9 ; *Uveitis/drug therapy ; *Wet Macular Degeneration/drug therapy ; Prospective Studies ; },
abstract = {PURPOSE: To identify factors associated with intraocular inflammation (IOI) in patients with neovascular age-related macular degeneration (nAMD) treated with brolucizumab.<br><br>METHODS: In this prospective observational study, we collected aqueous humor samples from 96 eyes of 96 patients receiving treatment with brolucizumab; IOI subsequently developed in 19 eyes of 19 patients. To identify cytokines upregulated in eyes with subsequent development of IOI, we compared the aqueous humor cytokine levels between the IOI and non-IOI groups. We also collected plasma from 20 patients who developed IOI and 20 age- and sex-matched controls to identify differences in plasma biomarkers and the subfraction of CD4+ cells. Using stepwise variable selection and multivariate binary regression analysis, we developed an algorithm that accurately assessed the likelihood of IOI occurrence.<br><br>RESULTS: The IOI group showed elevated aqueous humor levels of P-selectin (584 vs. 324 pg/mL, P = 0.013), TNF-&#x3b1; (0.89 vs. 0.60 pg/mL, P = 0.018), and IL-1&#x3b1; (2.0 vs. 1.4 pg/mL, P = 0.035) compared with the non-IOI group. Serum MMP-9 concentrations were higher in the IOI group than the non-IOI group (18,310 vs. 13,450 pg/mL, P = 0.029). Furthermore, the percentage of Th2 cells was significantly decreased in the IOI compared with the non-IOI group (3.1% vs. 4.2%, P = 0.013). The receiver operating characteristic curves for the optimal models showed an area under the curve ranging from 0.71 to 0.89, indicating good performance.<br><br>CONCLUSIONS: The combination of elevated concentrations of multiple aqueous humor cytokines and of serum MMP-9 and a lower number of plasma Th2 cells is associated with brolucizumab-related IOI in patients with nAMD.},
}
@article {pmid38170082,
year = {2024},
author = {Wu, Z and Hodgson, LAB and Guymer, RH},
title = {Targeted High-Density Microperimetry Testing of Nascent Geographic Atrophy in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {2},
pages = {100419},
pmid = {38170082},
issn = {2666-9145},
abstract = {PURPOSE: To examine the effectiveness of a targeted high-density microperimetry testing strategy for detecting visual sensitivity abnormalities in eyes with nascent geographic atrophy (nGA) when compared with standard central microperimetry testing.<br><br>DESIGN: Observational study.<br><br>PARTICIPANTS: Three-hundred and twenty-one eyes from 176 individuals with nonneovascular age-related macular degeneration (AMD).<br><br>METHODS: Thirty-five eyes from 33 participants underwent targeted high-density microperimetry testing of atrophic lesions (either nGA or geographic atrophy [GA]) within a 1.75&#xb0; radius (or approximately 1000 &#x3bc;m diameter) region. Another cohort of 286 eyes from 143 participants with bilateral large drusen at baseline underwent standard microperimetry testing of the central 6&#xb0; radius region at 6-monthly intervals for up to 36 months and thus included eyes that developed nGA and GA over the follow-up. All eyes underwent 2 tests at each visit to evaluate intrasession measurement repeatability.<br><br>MAIN OUTCOME MEASURES: Magnitude of visual sensitivity abnormalities based on mean sensitivity (MS), pointwise sensitivity standard deviation (PSD), and the number of test locations with a threshold of &#x2264; 10 decibels (dB; or deep defects) in eyes with nGA, compared between eyes that underwent targeted high-density microperimetry testing and standard central microperimetry testing.<br><br>RESULTS: The magnitude of visual sensitivity abnormalities based on MS, PSD and the number of deep defects were all significantly greater in eyes with nGA using targeted, high-density microperimetry testing compared with eyes with nGA using standard central microperimetry testing (all P < 0.001) and were all significantly less than eyes with GA using targeted, high-density microperimetry testing (all P &#x2264; 0.004). The intrasession coefficient of repeatability, where 95% of the test-retest differences are expected to occur, for MS in eyes with atrophic changes was 0.9 dB with the targeted, high-density microperimetry testing, and 1.8 dB with standard central microperimetry testing.<br><br>CONCLUSIONS: Targeted, high-density microperimetry testing enabled the detection of a significantly greater magnitude of visual sensitivity abnormalities in eyes with nGA than standard microperimetry testing.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38168310,
year = {2023},
author = {DiCesare, SM and Ortega, AJ and Collier, GE and Daniel, S and Thompson, KN and McCoy, MK and Posner, BA and Hulleman, JD},
title = {GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38168310},
issn = {2692-8205},
support = {P30 EY030413/EY/NEI NIH HHS/United States ; R01 EY027785/EY/NEI NIH HHS/United States ; },
abstract = {Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy (ML/DHRD) is an age-related macular degeneration (AMD)-like retinal dystrophy caused by an autosomal dominant R345W mutation in the secreted glycoprotein, fibulin-3 (F3). To identify new small molecules that reduce F3 production from retinal pigmented epithelium (RPE) cells, we knocked-in a luminescent peptide tag (HiBiT) into the endogenous F3 locus which enabled simple, sensitive, and high throughput detection of the protein. The GSK3 inhibitor, CHIR99021 (CHIR), significantly reduced F3 burden (expression, secretion, and intracellular levels) in immortalized RPE and non-RPE cells. Low-level, long-term CHIR treatment promoted remodeling of the RPE extracellular matrix (ECM), reducing sub-RPE deposit-associated proteins (e.g., amelotin, complement component 3, collagen IV, and fibronectin), while increasing RPE differentiation factors (e.g., tyrosinase, and pigment epithelium derived factor). In vivo, treatment of 8 mo R345W[+/+] knockin mice with CHIR (25 mg/kg i.p., 1 mo) was well tolerated and significantly reduced R345W F3-associated AMD-like basal laminar deposit number and size, thereby preventing the main pathological feature in these mice. This is the first demonstration of small molecule-based prevention of AMD-like pathology in ML/DHRD mice and may herald a rejuvenation of interest in GSK3 inhibition for the treatment of neurodegenerative diseases, including, potentially AMD itself.},
}
@article {pmid38165703,
year = {2024},
author = {Martinez Villarruel Hinnerskov, J and Krogh Nielsen, M and Kai Thomsen, A and Steffensen, MA and Honoré, B and Vorum, H and Nissen, MH and Sørensen, TL},
title = {Chemokine Receptor Profile of T Cells and Progression Rate of Geographic Atrophy Secondary to Age-related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {65},
number = {1},
pages = {5},
pmid = {38165703},
issn = {1552-5783},
mesh = {Humans ; *Geographic Atrophy/etiology/genetics ; *Macular Degeneration/pathology ; Fundus Oculi ; Genotype ; Polymorphism, Single Nucleotide ; Disease Progression ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: Geographic atrophy (GA) secondary to age-related macular degeneration is a progressive retinal degenerative disease. Systemic chemokine receptors and known risk-associated single-nucleotide polymorphisms have been associated with GA pathogenesis. Because halting progression is pivotal for patients, we investigated the association of candidate chemokine receptors and progression rate (PR) of atrophic lesions in patients with GA.<br><br>METHODS: This prospective observational study conducted at a single center included 85 patients with GA and 45 healthy controls. Patients were followed up after 13 months on average. Serial fundus autofluorescence images were used to determine the PR of atrophic lesions. The proportion of chemokine receptors on peripheral lymphocytes were determined by flow cytometric analysis.<br><br>RESULTS: Patients with GA had a lower proportion of CCR6 on CD8+T cells compared to healthy controls. Importantly, the proportion of CCR6 on CD4+T cells was lower in patients with fast GA progression compared to patients with slow progression of disease, suggesting that dysregulation of CCR6 could be involved in progression of GA. We also found that GA patients had a markedly higher percentage of CCR5 on CD4+ and CD8+T cells compared to healthy controls. After stratification according to ARMS2 polymorphism, we found a significantly lower level of CCR5 on CD8+T cells among patients with high-risk genotypes compared with patients with the low-risk genotype.<br><br>CONCLUSIONS: Our study finds that chemokine receptors are dysregulated in patients with GA and that CCR6 might be involved in GA progression, making it a potential target for intervention.},
}
@article {pmid38165600,
year = {2024},
author = {Sasso, P and Savastano, A and Vidal-Aroca, F and Minnella, AM and Francione, G and Sammarco, L and Cima, V and Ghiraldelli, R and Mattei, R and Rizzo, S},
title = {Enhancing the Functional Performance of Patients with Late-Stage Age-Related Macular Degeneration Implanted with a Miniature Telescope using Rehabilitation Training.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {3},
pages = {697-707},
pmid = {38165600},
issn = {2193-8245},
abstract = {INTRODUCTION: In this work, our aim is to report the functional outcomes of cataract surgery with smaller-incision new-generation miniature telescope (SING IMT) implantation followed by rehabilitation training in patients with central visual loss due to late-stage age-related macular degeneration (AMD).<br><br>METHODS: This retrospective study included patients who were monocularly implanted with SING IMT and then followed a rehabilitation program based on 6 biweekly sessions focused on visual abilities, reading, writing, visual motor integration and mobility. A total of 11 participants were included in this study. Reading acuity (RA), reading speed (RS), and fixation stability (FS) were assessed biweekly at 6-, 8-, 10-, 12-, 14-, and 16-week follow-up visits after SING IMT implantation and at a final assessment at 24&#xa0;weeks. Best-corrected distance visual acuity (BCDVA) was also measured at baseline and at the same postoperative timepoints.<br><br>RESULTS: Mean baseline BCDVA was 12.5&#x2009;&#xb1;&#x2009;8.6 letter score. Both RA and RS were found to be significantly improved from the first rehabilitation session (6&#xa0;weeks after surgery) to the last session (24&#xa0;weeks after surgery). At the end of the rehabilitation program, mean RA was 0.45&#x2009;&#xb1;&#x2009;0.19 LogMAR and mean RS was 30.9&#x2009;&#xb1;&#x2009;17.6 words per minute. Moreover, all patients achieved a FS of 15&#xa0;s or more after the last rehabilitation session. Most patients (55%) achieved an improvement of 15 letters in BCDVA at the end of the study.<br><br>CONCLUSIONS: This study suggests that rehabilitation training can improve visual functions of patients with late-stage AMD implanted with SING IMT in real-world tasks such as reading skills.},
}
@article {pmid38165050,
year = {2024},
author = {Yang, WQ and Ge, JY and Zhang, X and Zhu, WY and Lin, L and Shi, Y and Xu, B and Liu, RJ},
title = {THUMPD2 catalyzes the N2-methylation of U6 snRNA of the spliceosome catalytic center and regulates pre-mRNA splicing and retinal degeneration.},
journal = {Nucleic acids research},
volume = {52},
number = {6},
pages = {3291-3309},
pmid = {38165050},
issn = {1362-4962},
support = {2020YFA0803400//National Key Research and Development Program of China/ ; 31971230//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Humans ; Methylation ; Nucleic Acid Conformation ; *Retinal Degeneration/metabolism ; *RNA Precursors/genetics/metabolism ; *RNA Splicing/genetics ; RNA, Small Nuclear/metabolism ; *RNA-Binding Proteins ; Saccharomyces cerevisiae/genetics ; Spliceosomes/genetics/metabolism ; },
abstract = {The mechanisms by which the relatively conserved spliceosome manages the enormously large number of splicing events that occur in humans (∼200 000 versus ∼300 in yeast) are poorly understood. Here, we show deposition of one RNA modification-N2-methylguanosine (m2G) on the G72 of U6 snRNA (the catalytic center of the spliceosome) promotes efficient pre-mRNA splicing activity in human cells. This modification was identified to be conserved among vertebrates. Further, THUMPD2 was demonstrated as the methyltransferase responsible for U6 m2G72 by explicitly recognizing the U6-specific sequences and structural elements. The knock-out of THUMPD2 eliminated U6 m2G72 and impaired the pre-mRNA splicing activity, resulting in thousands of changed alternative splicing events of endogenous pre-mRNAs in human cells. Notably, the aberrantly spliced pre-mRNA population elicited the nonsense-mediated mRNA decay pathway. We further show that THUMPD2 was associated with age-related macular degeneration and retinal function. Our study thus demonstrates how an RNA epigenetic modification of the major spliceosome regulates global pre-mRNA splicing and impacts physiology and disease.},
}
@article {pmid38164223,
year = {2023},
author = {Hou, H and Durbin, MK and El-Nimri, N and Fischer, JL and Sadda, SR},
title = {Agreement, repeatability, and reproducibility of quantitative retinal layer assessment using swept-source and spectral-domain optical coherence tomography in eyes with retinal diseases.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1281751},
pmid = {38164223},
issn = {2296-858X},
abstract = {PURPOSE: To evaluate the agreement and precision of retinal thickness measurements obtained using swept-source optical coherence tomography (SS-OCT) and spectral-domain OCT (SD-OCT) in healthy eyes and eyes with retinopathy.<br><br>METHODS: This cross-sectional prospective study involved three DRI-OCT Triton (SS-OCT) and three 3D-OCT-1 Maestro (SD-OCT) devices. One of each device (Maestro and Triton) was paired with a single operator. Healthy subjects and patients with retinal diseases were recruited, with study eye and testing order randomized. At least 3 scans per eye were captured for wide scan (12&#x2009;mm&#x2009;&#xd7;&#x2009;9&#x2009;mm-Triton and Maestro) and macular cube scan (7&#x2009;mm&#x2009;&#xd7;&#x2009;7&#x2009;mm-Triton, 6&#x2009;mm&#x2009;&#xd7;&#x2009;6&#x2009;mm-Maestro). Thickness of the full retina, ganglion cell layer + inner plexiform layer (GCL+), and ganglion cell complex (GCL++) were obtained from wide scan and cube scans. Agreement of the measurements between the Triton and Maestro was evaluated by Bland-Altman analysis and Deming regression for each group. Repeatability and reproducibility were assessed using a two-way random effect analysis of variance (ANOVA) model for each parameter by group.<br><br>RESULTS: Twenty-five healthy subjects (25 eyes) and 26 patients with retinal diseases (26 eyes), including, but not limited to, age-related macular degeneration, macular hole, and diabetic retinopathy were recruited. Overall, the measurement differences between Triton and Maestro were <6&#x2009;&#x3bc;m (mean differences of full retina, GCL++, and GCL+ thickness were &#x2264;5.5&#x2009;&#x3bc;m, 1.3&#x2009;&#x3bc;m, and 2.8&#x2009;&#x3bc;m, respectively) and not statistically significant across the parameters. The repeatability and reproducibility estimates indicate high precision in both devices and groups. Across all the parameters, the repeatability limit was &#x2264;7.6&#x2009;&#x3bc;m for Triton and &#x2264;12.7&#x2009;&#x3bc;m for Maestro; reproducibility limit was &#x2264;9.2&#x2009;&#x3bc;m for Triton and &#x2264;14.4&#x2009;&#x3bc;m for Maestro. In eyes with retinal pathology, the repeatability coefficient of variation (CV)% was &#x2264;2.6% for Triton and &#x2264;3.4% for Maestro; reproducibility CV% was &#x2264;3.3% for Triton and &#x2264;3.5% for Maestro.<br><br>CONCLUSION: Both Triton SS-OCT and Maestro SD-OCT provide reliable measurements of retinal thickness in healthy eyes and eyes with retinal diseases. Excellent agreement between the two devices indicates interoperability when testing healthy eyes or eyes with retinal pathology. These findings support the use of thickness measurements from Triton SS-OCT and Maestro SD-OCT in clinical practice.},
}
@article {pmid38160882,
year = {2024},
author = {Humayun, MS and Clegg, DO and Dayan, MS and Kashani, AH and Rahhal, FM and Avery, RL and Salehi-Had, H and Chen, S and Chan, C and Palejwala, N and Ingram, A and Mitra, D and Pennington, BO and Hinman, C and Faynus, MA and Bailey, JK and Johnson, LV and Lebkowski, JS},
title = {Long-term Follow-up of a Phase 1/2a Clinical Trial of a Stem Cell-Derived Bioengineered Retinal Pigment Epithelium Implant for Geographic Atrophy.},
journal = {Ophthalmology},
volume = {131},
number = {6},
pages = {682-691},
doi = {10.1016/j.ophtha.2023.12.028},
pmid = {38160882},
issn = {1549-4713},
mesh = {Humans ; *Geographic Atrophy/surgery/physiopathology ; *Retinal Pigment Epithelium/transplantation/pathology ; Aged ; *Visual Acuity/physiology ; Female ; Aged, 80 and over ; Male ; Follow-Up Studies ; Tomography, Optical Coherence ; Human Embryonic Stem Cells/transplantation/cytology ; Stem Cell Transplantation ; Treatment Outcome ; },
abstract = {PURPOSE: To report long-term results from a phase 1/2a clinical trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA).<br><br>DESIGN: A single-arm, open-label phase 1/2a clinical trial approved by the United States Food and Drug Administration.<br><br>PARTICIPANTS: Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], &#x2264; 20/200) as a result of GA involving the fovea.<br><br>METHODS: The clinical trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly.<br><br>MAIN OUTCOME MEASURES: Safety was the primary endpoint of the study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells.<br><br>RESULTS: At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes.<br><br>CONCLUSIONS: This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38160880,
year = {2024},
author = {Xue, CC and Sim, R and Chee, ML and Yu, M and Wang, YX and Rim, TH and Hyung, PK and Woong, KS and Song, SJ and Nangia, V and Panda-Jonas, S and Wang, NL and Hao, J and Zhang, Q and Cao, K and Sasaki, M and Harada, S and Toru, T and Ryo, K and Raman, R and Surya, J and Khan, R and Bikbov, M and Wong, IY and Cheung, CMG and Jonas, JB and Cheng, CY and Tham, YC},
title = {Is Kidney Function Associated with Age-Related Macular Degeneration?: Findings from the Asian Eye Epidemiology Consortium.},
journal = {Ophthalmology},
volume = {131},
number = {6},
pages = {692-699},
doi = {10.1016/j.ophtha.2023.12.030},
pmid = {38160880},
issn = {1549-4713},
mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; *Glomerular Filtration Rate ; Middle Aged ; *Renal Insufficiency, Chronic/epidemiology/physiopathology ; Aged ; *Macular Degeneration/physiopathology/epidemiology ; Risk Factors ; Asian People/ethnology ; Adult ; Odds Ratio ; Prevalence ; Aged, 80 and over ; },
abstract = {PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium.<br><br>DESIGN: Cross-sectional study.<br><br>PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies.<br><br>METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m[2]. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups.<br><br>MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD.<br><br>RESULTS: Among 51 253 participants (mean age, 54.1 &#xb1; 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P&#xa0;= 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P&#xa0;= 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P &#x2265; 0.149).<br><br>CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38160808,
year = {2024},
author = {Kal, S and Mahata, S and Jati, S and Mahata, SK},
title = {Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.},
journal = {Peptides},
volume = {172},
number = {},
pages = {171147},
pmid = {38160808},
issn = {1873-5169},
support = {I21 RX004398/RX/RRD VA/United States ; R21 AG078635/AG/NIA NIH HHS/United States ; R21 AG080246/AG/NIA NIH HHS/United States ; },
mesh = {Male ; Female ; Pregnancy ; Humans ; Hypoglycemic Agents ; *Diabetes Mellitus, Type 1 ; *Diabetes Mellitus, Type 2 ; *Diabetes, Gestational ; Thymine ; Peptides/metabolism ; DNA, Mitochondrial/genetics ; RNA, Ribosomal/genetics ; Guanine ; },
abstract = {Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins encoded by short open-reading frames (sORF) in mitochondrial DNA (mtDNA). Currently, three types of MDPs have been identified: Humanin (HN), MOTS-c (Mitochondrial ORF within Twelve S rRNA type-c), and SHLP1-6 (small Humanin-like peptide, 1 to 6). The 12 S ribosomal RNA (MT-RNR1) gene harbors the sequence for MOTS-c, whereas HN and SHLP1-6 are encoded by the 16 S ribosomal RNA (MT-RNR2) gene. Special genetic codes are used in mtDNA as compared to nuclear DNA: (i) ATA and ATT are used as start codons in addition to the standard start codon ATG; (ii) AGA and AGG are used as stop codons instead of coding for arginine; (iii) the standard stop codon UGA is used to code for tryptophan. While HN, SHLP6, and MOTS-c are encoded by the H (heavy owing to high guanine + thymine base composition)-strand of the mtDNA, SHLP1-5 are encoded by the L (light owing to less guanine + thymine base composition)-strand. MDPs attenuate disease pathology including Type 1 diabetes (T1D), Type 2 diabetes (T2D), gestational diabetes, Alzheimer's disease (AD), cardiovascular diseases, prostate cancer, and macular degeneration. The current review will focus on the MDP regulation of T2D, T1D, and gestational diabetes along with an emphasis on the evolutionary pressures for conservation of the amino acid sequences of MDPs.},
}
@article {pmid38160737,
year = {2024},
author = {Feo, A and Stradiotto, E and Sacconi, R and Menean, M and Querques, G and Romano, MR},
title = {Subretinal hyperreflective material in retinal and chorioretinal disorders: A comprehensive review.},
journal = {Survey of ophthalmology},
volume = {69},
number = {3},
pages = {362-377},
doi = {10.1016/j.survophthal.2023.10.013},
pmid = {38160737},
issn = {1879-3304},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnosis ; *Choroid Diseases/diagnosis ; *Fluorescein Angiography/methods ; Multimodal Imaging/methods ; Retina/pathology/diagnostic imaging ; },
abstract = {Subretinal hyperreflective material (SHRM) is a common and remarkable optical coherence tomography (OCT) biomarker whose importance is emerging in several retinal and chorioretinal diseases, including age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, pathologic myopia, posterior uveitis, vitelliform lesions and macular dystrophies, and rarer disorders. Multimodal imaging, also thanks to the introduction of OCT angiography, allowed a deeper characterisation of SHRM components and its morphological changes after treatment, suggesting its usefulness in clinical practice. We discuss and summarize the nature, multimodal imaging characteristics, and prognostic and predictive significance of SHRM in the different retinal and choroidal disorders in which it has been described.},
}
@article {pmid38158173,
year = {2024},
author = {Anderson, BD and Lee, TT and Bell, BA and Wang, T and Dunaief, JL},
title = {Optimizing the sodium iodate model: Effects of dose, gender, and age.},
journal = {Experimental eye research},
volume = {239},
number = {},
pages = {109772},
pmid = {38158173},
issn = {1096-0007},
support = {S10 OD026860/OD/NIH HHS/United States ; T32 GM008076/GM/NIGMS NIH HHS/United States ; T32 EY007035/EY/NEI NIH HHS/United States ; R01 EY028916/EY/NEI NIH HHS/United States ; R01 EY015240/EY/NEI NIH HHS/United States ; T32 EY007132/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; },
mesh = {Female ; Male ; Mice ; Animals ; Retina/pathology ; *Retinal Degeneration/chemically induced/pathology ; *Macular Degeneration/drug therapy/pathology ; Iodates/toxicity ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/pathology ; Disease Models, Animal ; },
abstract = {Sodium iodate (NaIO3) is a commonly used model for age-related macular degeneration (AMD), but its rapid and severe induction of retinal pigment epithelial (RPE) and photoreceptor degeneration can lead to the premature dismissal of potentially effective therapeutics. Additionally, little is known about how sex and age affect the retinal response to NaIO3. This study aims to establish a less severe yet reproducible regimen by testing low doses of NaIO3 while considering age- and sex-related effects, enabling a broader range of therapeutic evaluations. In this study, young (3-5 months) and old (18-24 months) male and female C57Bl/6J mice were given an intraperitoneal (IP) injection of 15, 20, or 25 mg/kg NaIO3. Damage assessment one week post-injection included in vivo imaging, histological examination, and qRT-PCR analysis. The results revealed that young mice showed no damage at 15 mg/kg IP NaIO3, with varying degrees of damage observed at 20 mg/kg. At 25 mg/kg, most young mice displayed widespread retinal damage, with females exhibiting less retinal thinning than males. In contrast, older mice at 20 and 25 mg/kg displayed a more patchy degeneration pattern, outer retinal undulations, and greater variability in degeneration than the young mice. The most effective model for minimizing damage while maintaining consistency utilizes young female mice injected with 25 mg/kg NaIO3. The observed sex- and age-related differences underscore the importance of considering these variables in research, aligning with the National Institutes of Health's guidance. While the model does not fully replicate the complexity of AMD, these findings enhance its utility as a valuable tool for testing RPE/photoreceptor protective or replacement therapies.},
}
@article {pmid38155139,
year = {2023},
author = {Fedirko, P and Babenko, T and Kuts, K and Pilmane, M and Yunga, A and Garkava, N},
title = {BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT. PART V - ORGANIC AND FUNCTIONAL CHANGES CORRELATION ON THE EXAMPLE OF CERTAIN DISEASES.},
journal = {Problemy radiatsiinoi medytsyny ta radiobiolohii},
volume = {28},
number = {},
pages = {431-443},
doi = {10.33145/2304-8336-2023-28-431-443},
pmid = {38155139},
issn = {2313-4607},
mesh = {Humans ; *Chernobyl Nuclear Accident ; *Radiation Injuries/epidemiology/etiology/pathology ; *Radiation Exposure/adverse effects ; Radiation, Ionizing ; *Macular Degeneration ; Radiation Dosage ; },
abstract = {The question about correlation between organic and functional changes in persons, exposed to radiation is still insufficiently studied. Dynamics of morbidity for different forms and classes of non-tumour diseases periodisation, proposed by epidemiologists, suggests the identification of three main periods: «early» (the first 6 post-Chornobyl accident years); «distant» (12-21 years) and «late» (22-30 years). However, the correspondence this periodisation to the results of epidemiological data, without taking into account the clinical features of the diseases, may contribute to the impression, that in the first period after a radiation disaster functional disorders (or autonomic regulation disorders, etc.) prevail in all cases. Meanwhile, the data from ophthalmological and neurological studies, which we aim to demonstrate in this paper, rather indicate the presence of a significant morphological basis for the development of functional disorders in early period after a radiation disaster. The objective of this work is analyse modern experimental, epidemiological and clinical data on the correlation between organic and functional changes, characteristic of radiation cerebro-ophthalmological effects - radiation cataracts, age-related macular degeneration, cerebral small vessel disease, and neurocognitive deficits. Materials and methods. The criteria for inclusion in the analytical review were peer-reviewed publications in PubMed/MEDLINE, Scopus, Web of Science, and manually selected papers; the results of our own research were also used. An additional analysis of the results of examinations conducted in 1991-2004 was performed, which included a total of 11 123 persons irradiated as the result of catastrophy at the Chornobyl NPP. Results. In the first period of radiation cataract development, which is a specific consequence of radiation exposure, morphological changes (lens opacities) are observed, which lead to a decrease in visual function only later. Analysing the correlation between organic and functional changes in the development of diseases, for which ionising radiation exposure is a significant risk factor, we observe a similar picture. For example, CSVD associated with arterial hypertension may be a manifestation of accelerated aging associated with exposure to ionising radiation.Similarly, the initial signs of age-related macular degeneration in radiation-exposed individuals are usually manifested by changes in the morphology of the retina, choroid, and pigment epithelium in the macular area, while functional disorders in the form of decreased central vision and metamorphopsia, etc., occur later.},
}
@article {pmid38155129,
year = {2023},
author = {Yefimova, Y and Fedirko, P and Babenko, T and Dorichevska, R},
title = {PREVALENCE OF AGE-MACULAR DEGENERATION IN PERSONS OF WORKING AGE WHO APPLIED TO PARTICIPATE IN WORK IN ACTION CONDITIONS IONIZING RADIATION: PRELIMINARY RESULTS.},
journal = {Problemy radiatsiinoi medytsyny ta radiobiolohii},
volume = {28},
number = {},
pages = {277-285},
doi = {10.33145/2304-8336-2023-28-277-285},
pmid = {38155129},
issn = {2313-4607},
mesh = {Humans ; Middle Aged ; Aged ; Retrospective Studies ; Prevalence ; *Macular Degeneration/epidemiology/etiology ; Radiation, Ionizing ; World Health Organization ; },
abstract = {UNLABELLED: In recent decades, several large-scale epidemiological surveys of the eyes have been conducted to determine the global prevalence of retinal degenerative diseases (for example, the Blue Mountains Eye Study). The results of such studies were evaluated several decades, and the studies themselves required significant material resources. Such large-scale projects have not been carried out in Ukraine.Objective of the work is to study the prevalence of age-related macular degeneration in a pilot group of non-irradiated persons of working age to determine the suitability of using the results for further epidemiological studies in Ukraine.<br><br>MATERIALS AND METHODS: A retrospective-prospective analysis of the prevalence of degenerative diseases of the retina in a pilot group of persons who underwent an in-depth examination, as they claimed to participate in works in harmful conditions (with ionizing radiation) was carried out. The results of primary ophthalmological examinations of 1,064 people, conducted between January 18, 2007 and October 29, 2009, were randomly selected. The age of the examinees at the time of examination ranged from 18.94 to 67.49 years, the number of persons aged 18 to 30, 30 to 40, and 40 to 50 years was approximately the same. The results of a standardized ophthalmological examination were used.<br><br>RESULTS: In the pilot group of people in working age, the prevalence of age-related macular degeneration was 196.4 per 1,000 people. Hazard analysis showed that the relative risk of age-related macular degeneration increased with age and was 1.14 (95% CI 1.07-1.21) for individuals aged 30-39 years; in comparison with persons under the age of 30; 1.3 (95% CI 1.21-1.41) - for persons aged 40-49; 1.3 (95% CI 1.18-1.52) - for persons aged 50-59; 1.86 (95% CI 1.0-3.47) - for persons over 60 years of age. The odds ratio (OR) of having age-related macular degeneration for those aged 30-39 years compared with those younger than 30 years was 3.04 (95% CI 1.79-5.15); for persons aged 40-49 years - 5.49 (95% CI 3.31-9.09); for persons aged 50-59 years - 6.04 (95% CI 3.36-10.88); for persons aged 50-59 years - 6.04 (95% CI 3.36-10.88) and for persons older than 60 years - 13.71 (95% CI 3.68-51.15), p in all cases < 0.0001.<br><br>CONCLUSIONS: It was established that the prevalence of age-related macular degeneration in non-irradiated individuals determined in the pilot group was high and statistically significantly increased with age. It is shown that the results of primary ophthalmological examinations of a pilot group of persons who applied for participation in works in harmful conditions (with ionizing radiation) are suitable for epidemiological studies of the frequency and course of degenerative retinal diseases in persons of working age in Ukraine. The obtained results are important for practical medicine, as they will allow us to assess the prospects needs for medical care in the secondary and tertiary care.},
}
@article {pmid38154619,
year = {2024},
author = {Trinh, M and Cheung, R and Duong, A and Nivison-Smith, L and Ly, A},
title = {OCT Prognostic Biomarkers for Progression to Late Age-related Macular Degeneration: A Systematic Review and Meta-analysis.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {6},
pages = {553-565},
doi = {10.1016/j.oret.2023.12.006},
pmid = {38154619},
issn = {2468-6530},
mesh = {Humans ; *Disease Progression ; Prognosis ; *Tomography, Optical Coherence/methods ; Biomarkers/metabolism ; Macular Degeneration/diagnosis/metabolism ; },
abstract = {TOPIC: To evaluate which OCT prognostic biomarkers best predict the risk of progression from early/intermediate to late age-related macular degeneration (AMD).<br><br>CLINICAL RELEVANCE: Among > 100 OCT prognostic biomarkers for AMD, it is unclear which are the most relevant for clinicians and researchers to focus on. This review evaluated which OCT biomarkers confer the greatest magnitude of prediction for progression to late AMD.<br><br>METHODS: Study protocol was registered on PROSPERO (CRD42023400166). PubMed and Embase were searched from inception to March 2, 2023, and eligible studies assessed following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was any quantified risk of progression from treatment-naive early/intermediate AMD to late AMD, including hazard ratios (HRs), odds ratios (ORs), and standardized mean differences (at baseline, between eyes with versus without progression), subgrouped by each OCT biomarker. Further meta-analyses were subgrouped by progression to geographic atrophy or neovascularization.<br><br>RESULTS: A total of 114 quantified OCT prognostic biomarkers were identified. With high GRADE certainty of evidence, the greatest magnitudes of prediction to late AMD belonged to: external limiting membrane abnormality (OR, 15.42 [7.63, 31.17]), ellipsoid zone abnormality (OR, 10.8 [4.58, 25.46]), interdigitation zone abnormality (OR, 7.68 [2.57, 23]), concurrent large drusen and reticular pseudodrusen (HR, 6.73 [1.35, 33.65], hyporeflective drusen cores (HR, 2.48 [1.8, 3.4]; OR 1.85 [1.29, 2.66]), intraretinal hyperreflective foci (IHRF; HR, 2.16 [0.92, 5.07]; OR 5.08 [3.26, 7.92]), and large drusen (HR, 2.01 [1.35, 2.99]); OR, 1.98 [1.27, 3.08]). There was greater risk of geographic atrophy for IHRF and hyporeflective drusen cores (P < 0.05), and neovascularization for ellipsoid zone abnormality (P < 0.05). Other OCT biomarkers such as drusenoid pigment epithelium detachment, shallow irregular retinal pigment epithelium elevations, and nascent geographic atrophy exhibited large magnitudes of risk but required further studies for validation.<br><br>CONCLUSION: This review synthesizes the 6 most relevant OCT prognostic biomarkers for AMD with greater predictive ability than large drusen alone, for clinicians and researchers to focus on. Further study is required to validate other biomarkers with less than high certainty of evidence, and assess how the copresence of biomarkers may affect risks.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid38153807,
year = {2024},
author = {Carozza, G and Zerti, D and Tisi, A and Ciancaglini, M and Maccarrone, M and Maccarone, R},
title = {An overview of retinal light damage models for preclinical studies on age-related macular degeneration: identifying molecular hallmarks and therapeutic targets.},
journal = {Reviews in the neurosciences},
volume = {35},
number = {3},
pages = {303-330},
pmid = {38153807},
issn = {2191-0200},
mesh = {Animals ; Humans ; *Macular Degeneration/drug therapy/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been fully elucidated yet. Due to the complexity and to the multiple features of the disease, many efforts have been made to develop animal models which faithfully reproduce the overall AMD hallmarks or that are able to mimic the different AMD stages. In this context, light damage (LD) rodent models of AMD represent a suitable and reliable approach to mimic the different AMD forms (dry, wet and geographic atrophy) while maintaining the time-dependent progression of the disease. In this review, we comprehensively reported how the LD paradigms reproduce the main features of human AMD. We discuss the capability of these models to broaden the knowledge in AMD research, with a focus on the mechanisms and the molecular hallmarks underlying the pathogenesis of the disease. We also critically revise the remaining challenges and future directions for the use of LD models.},
}
@article {pmid38153747,
year = {2023},
author = {Moir, J and Hyman, MJ and Wang, J and Shah, A and Maatouk, C and Flores, A and Skondra, D},
title = {Associations Between Autoimmune Disease and the Development of Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {15},
pages = {45},
pmid = {38153747},
issn = {1552-5783},
mesh = {United States/epidemiology ; Humans ; Aged ; *Crohn Disease ; Medicare ; *Autoimmune Diseases/complications/epidemiology ; *Lupus Erythematosus, Systemic/complications/epidemiology ; *Macular Degeneration/diagnosis/epidemiology/etiology ; },
abstract = {PURPOSE: The pathogenesis of age-related macular degeneration (AMD) likely implicates the dysregulation of immune response pathways. Several studies demonstrate that the pathogenic elements of AMD resemble those of autoimmune diseases, yet the association between AMD development and most autoimmune diseases remain unexplored.<br><br>METHODS: We conducted a case-control analysis of patients ages 55 and older with new-onset International Classification of Diseases (ICD) coding of dry, wet, or unspecified AMD between 2005 and 2019 in the Merative MarketScan Commercial and Medicare Databases. The diagnosis of an autoimmune disease was defined by an outpatient or inpatient claim with a relevant ICD code in the 12&#xa0;months before the index visit. Conditional multivariable logistic regression, adjusted for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals.<br><br>RESULTS: We identified 415,027 cases with new-onset ICD coding for AMD matched with propensity scores to 414,853 controls. In total, 16.1% of cases and 15.9% of controls were diagnosed with any autoimmune disease. The diagnosis of any autoimmune disease did not affect the odds of new-onset ICD coding for AMD in multivariable regression (OR = 1.01; 95% CI, 0.999-1.02). Discoid lupus erythematosus (OR = 1.29; 95% CI, 1.12-1.48), systemic lupus erythematosus (SLE) (OR = 1.21; 95% CI, 1.15-1.27), giant cell arteritis (OR = 1.19; 95% CI, 1.09-1.30), Sjogren's syndrome (OR = 1.17; 95% CI, 1.09-1.26), and Crohn's disease (OR = 1.13; 95% CI, 1.06-1.22) increased the odds of a new-onset ICD coding for AMD.<br><br>CONCLUSIONS: Most autoimmune diseases do not affect the odds of developing AMD but several common autoimmune disorders such as SLE and Crohn's disease were associated with modestly increased odds of AMD. Further studies are needed to validate and investigate the underlying mechanisms of these associations.},
}
@article {pmid38153745,
year = {2024},
author = {Zhang, S and Chen, Y and Li, Z and Wang, W and Xuan, M and Zhang, J and Hu, Y and Chen, Y and Xiao, O and Yin, Q and Zheng, Y and He, M and Han, X},
title = {Axial Elongation Trajectories in Chinese Children and Adults With High Myopia.},
journal = {JAMA ophthalmology},
volume = {142},
number = {2},
pages = {87-94},
pmid = {38153745},
issn = {2168-6173},
mesh = {Child ; Female ; Adolescent ; Young Adult ; Humans ; Aged ; Adult ; Cohort Studies ; Follow-Up Studies ; Visual Acuity ; *Myopia, Degenerative/diagnosis/complications ; *Macular Degeneration/complications ; China/epidemiology ; Atrophy/complications ; },
abstract = {IMPORTANCE: Understanding the long-term axial elongation trajectory in high myopia is important to prevent blindness.<br><br>OBJECTIVE: To evaluate axial elongation trajectories and related visual outcomes in children and adults with high myopia.<br><br>In this cohort study, participants in the Zhongshan Ophthalmic Centre-Brien Holden Vision Institute high myopia cohort were followed up every other year for 8 years. Participants with axial length measurements at baseline (2011 or 2012) and at least 1 follow-up visit were included. Participants were grouped according to baseline age as children and adolescents (7 to <18 years), young adults (18 to <40 years), and older adults (&#x2265;40 to 70 years). Data were analyzed from November 1, 2022, to June 1, 2023.<br><br>EXPOSURE: High myopia (spherical power &#x2264;-6.00 diopters).<br><br>MAIN OUTCOMES AND MEASURES: Longitudinal axial elongation trajectories were identified by cluster analysis. Axial elongation rates were calculated by linear mixed-effects models. A 2-sided P&#x2009;<&#x2009;.05 was defined as statistically significant.<br><br>RESULTS: A total of 793 participants (median [range] age, 17.8 [6.8-69.7] years; 418 females [52.7%]) and 1586 eyes were included in the analyses. Mean axial elongation rates were 0.46 mm/y (95% CI, 0.44-0.48 mm/y) for children and adolescents, 0.07 mm/y (95% CI, 0.06-0.09 mm/y) for young adults, and 0.13 mm/y (95% CI, 0.07-0.19 mm/y) for older adults. Cluster analysis identified 3 axial elongation trajectories, with the stable, moderate, and rapid progression trajectories having mean axial elongation rates of 0.02 mm/y (95% CI, 0.01-0.02 mm/y), 0.12 mm/y (95% CI, 0.11-0.13 mm/y), and 0.38 mm/y (95% CI, 0.35-0.42 mm/y), respectively. At 8 years of follow-up, compared with the stable progression trajectory, the rapid progression trajectory was associated with a 6.92 times higher risk of developing pathological myopic macular degeneration (defined as diffuse or patchy chorioretinal atrophy or macular atrophy; odds ratio, 6.92 [95% CI, 1.07-44.60]; P&#x2009;=&#x2009;.04), and it was associated with a 0.032 logMAR decrease in best-corrected visual acuity (&#x3b2;&#x2009;=&#x2009;0.032 [95% CI, 0.001-0.063]; P&#x2009;=&#x2009;.04).<br><br>CONCLUSIONS AND RELEVANCE: The findings of this 8-year follow-up study suggest that axial length in high myopia continues to increase from childhood to late adulthood following 3 distinct trajectories. At 8 years of follow-up, the rapid progression trajectory was associated with a higher risk of developing pathological myopic macular degeneration and poorer best-corrected visual acuity compared with the stable progression trajectory. These distinct axial elongation trajectories could prove valuable for early identification and intervention for high-risk individuals.},
}
@article {pmid38153708,
year = {2024},
author = {Tsang, JY and Wright, A and Carr, MJ and Dickinson, C and Harper, RA and Kontopantelis, E and Van Staa, T and Munford, L and Blakeman, T and Ashcroft, DM},
title = {Risk of Falls and Fractures in Individuals With Cataract, Age-Related Macular Degeneration, or Glaucoma.},
journal = {JAMA ophthalmology},
volume = {142},
number = {2},
pages = {96-106},
pmid = {38153708},
issn = {2168-6173},
mesh = {Humans ; Aged ; Cohort Studies ; *Cataract/epidemiology/complications ; *Glaucoma/epidemiology/complications ; *Macular Degeneration/diagnosis/epidemiology/complications ; },
abstract = {IMPORTANCE: Three leading disease causes of age-related visual loss are cataract, age-related macular degeneration (AMD), and glaucoma. Although all 3 eye diseases have been implicated with falls and fracture risk, evidence is mixed, with the contribution of different eye diseases being uncertain.<br><br>OBJECTIVE: To examine whether people with cataract, AMD, or glaucoma have higher risks of falls or fractures than those without.<br><br>This cohort study was a population-based study in England using routinely collected electronic health records from the Clinical Practice Research Datalink (CPRD) GOLD and Aurum primary care databases with linked hospitalization and mortality records from 2007 to 2020. Participants were people with cataract, AMD, or glaucoma matched to comparators (1:5) by age, sex, and general practice. Data were analyzed from May 2021 to June 2023.<br><br>EXPOSURES: For each eye disease, we estimated the risk of falls or fractures using separate multivariable Cox proportional hazards regression models.<br><br>MAIN OUTCOMES: Two primary outcomes were incident falls and incident fractures derived from general practice, hospital, and mortality records. Secondary outcomes were incident fractures of specific body sites.<br><br>RESULTS: A total of 410&#x202f;476 people with cataract, 75&#x202f;622 with AMD, and 90&#x202f;177 with glaucoma were matched (1:5) to 2&#x202f;034&#x202f;194 (no cataract), 375&#x202f;548 (no AMD), and 448&#x202f;179 (no glaucoma) comparators. The mean (SD) age was 73.8 (11.0) years, 79.4 (9.4) years, and 69.8 (13.1) years for participants with cataract, AMD, or glaucoma, respectively. Compared with comparators, there was an increased risk of falls in those with cataract (adjusted hazard ratio [HR], 1.36; 95% CI, 1.35-1.38), AMD (HR, 1.25; 95% CI, 1.23-1.27), and glaucoma (HR, 1.38; 95% CI, 1.35-1.41). Likewise for fractures, there were increased risks in all eye diseases, with an HR of 1.28 (95% CI, 1.27-1.30) in the cataract cohort, an HR of 1.18 (95% CI, 1.15-1.21) for AMD, and an HR of 1.31 (95% CI, 1.27-1.35) for glaucoma. Site-specific fracture analyses revealed increases in almost all body sites (including hip, spine, forearm, skull or facial bones, pelvis, ribs or sternum, and lower leg fractures) compared with matched comparators.<br><br>CONCLUSIONS AND RELEVANCE: The results of this study support recognition that people with 1 or more of these eye diseases are at increased risk of both falls and fractures. They may benefit from improved advice, access, and referrals to falls prevention services.},
}
@article {pmid38153666,
year = {2024},
author = {Xiang, W and Li, L and Zhao, Q and Zeng, Y and Shi, J and Chen, Z and Gao, G and Lai, K},
title = {PEDF protects retinal pigment epithelium from ferroptosis and ameliorates dry AMD-like pathology in a murine model.},
journal = {GeroScience},
volume = {46},
number = {2},
pages = {2697-2714},
pmid = {38153666},
issn = {2509-2723},
support = {82171066//National Natural Science Foundation of China/ ; 202102010333//Guangzhou Science and Technology Plan Project/ ; SL2024A03J00359//Guangzhou Science and Technology Plan Project/ ; 2021A1515010895//Guangdong Basic and Applied Basic Research Fund Project/ ; SL2023A04J00138//Guangdong Basic and Applied Basic Research Fund Project/ ; },
mesh = {Humans ; Mice ; Animals ; Aged ; *Retinal Pigment Epithelium/metabolism/pathology ; *Ferroptosis ; Disease Models, Animal ; Mice, Knockout ; *Eye Proteins ; *Nerve Growth Factors ; *Serpins ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision damage among elderly individuals. There is still no efficient treatment for dry AMD. Retinal pigment epithelial (RPE) degeneration has been confirmed to play an important role in dry AMD. Recent studies have reported that ferroptosis caused by iron overload and lipid peroxidation may be the primary causes of RPE degeneration. However, the upstream regulatory molecules of RPE ferroptosis remain largely unknown. Pigment epithelium-derived factor (PEDF) is an important endogenic protective factor for the RPE. Our results showed that in the murine dry AMD model induced by sodium iodate (SI), PEDF expression was downregulated. Moreover, dry AMD-like pathology was observed in PEDF-knockout mice. Therefore, the aim of this study was to reveal the effects and mechanism of PEDF on RPE ferroptosis and investigate potential therapeutic targets for dry AMD. The results of lipid peroxidation and transmission electron microscope showed that retinal ferroptosis was significantly activated in SI-treated mice and PEDF-knockout mice. Restoration of PEDF expression ameliorated SI-induced retinal dysfunction in mice, as assessed by electroretinography and optical coherence tomography. Mechanistically, western blotting and immunofluorescence analysis demonstrated that the overexpression of PEDF could upregulate the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain-1 (FTH1), which proved to inhibit lipid peroxidation and RPE ferroptosis induced by SI. This study revealed the novel role of PEDF in ferroptosis inhibition and indicated that PEDF might be a potential therapeutic target for dry AMD.},
}
@article {pmid38153512,
year = {2024},
author = {Chen, CH and Lim, PS and Wu, TK and Chuang, WL and Yu, TS and Tsai, FJ and Chen, CM and Chang, KH},
title = {Intravitreal ranibizumab injection is associated with an increased risk of chronic kidney disease: a population-based study in Taiwan.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {397},
number = {7},
pages = {4799-4808},
pmid = {38153512},
issn = {1432-1912},
support = {TTMHH-R1130010//Tungs' Taichung Metro Harbor hospital/ ; MOST 111-2321-B-039-005//Ministry of Science and Technology/ ; DMR-111-105//China Medical University Hospital/ ; },
mesh = {Humans ; Male ; Female ; Taiwan/epidemiology ; Middle Aged ; *Ranibizumab/administration &amp; dosage/adverse effects ; *Renal Insufficiency, Chronic/epidemiology ; Aged ; *Intravitreal Injections ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Adult ; Risk Factors ; Databases, Factual ; Cohort Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Retrospective Studies ; },
abstract = {Systemic vascular endothelial growth factor (VEGF) blockade has been the top adjunctive chemotherapy since 1990. Anti-VEGF therapy has also been associated with worsened renal function in some patients. However, the association between patient outcomes and use of intravitreal VEGF inhibitors remains controversial. Thus, it is necessary to determine the action mechanism and long-term renal effects of ranibizumab. The National Health Insurance Research Database (NHIRD) is one of the largest global databases that are extensively used for epidemiological research. NHIRD contains the medical information of all insureds, such as inpatient, outpatient, emergency, and traditional Chinese medicine records. We selected subjects aged ≥ 20 years who recently administered ranibizumab for the ranibizumab cohort. Non-ranibizumab cohort consisted of subjects who did not receive ranibizumab, and the index date was a random date between 2008 and 2018. We excluded subjects with missing sex and age records and those in which the date of primary outcome was before the index date. The two cohorts were matched via 1:1 propensity score matching based on sex, age, index year, hypertension, diabetes mellitus, hyperlipidemia, stroke, coronary artery disease, alcoholism, chronic obstructive pulmonary disease, and age-related macular degeneration, retinal vein occlusion, and diabetic macular edema. Medical confounders were angiotensin I-converting enzyme inhibitors, statins, corticosteroids, VEGF inhibitors including bevacizumab and aflibercept, lithium, amphotericin B, adefovir, NSAIDS, cisplatin, and calcineurin inhibitors. Among 48,248 participants aged ≥ 20 years, 24,136 (50%) received ranibizumab (13,565 male [56.20%] and 10,571 female [43.80%]). Moreover, 24,136 participants who did not receive ranibizumab were matched by age, sex, comorbidities, and medications. Subjects who received ranibizumab exhibited a significantly higher risk of CKD than those who did not receive ranibizumab (adjusted hazard ratio = 1.88, 95% CI = 1.79-1.96). Our findings revealed that exposure to intravitreal ranibizumab is an independent risk factor for CKD. Therefore, physicians and ophthalmologists should make the patients aware of such a correlation to increase patient safety and decrease the CKD burden.},
}
@article {pmid38152412,
year = {2024},
author = {Khanani, AM and Boyer, DS and Wykoff, CC and Regillo, CD and Busbee, BG and Pieramici, D and Danzig, CJ and Joondeph, BC and Major, JC and Turpcu, A and Kiss, S},
title = {Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective, two-year, multicentre phase 1 study.},
journal = {EClinicalMedicine},
volume = {67},
number = {},
pages = {102394},
pmid = {38152412},
issn = {2589-5370},
abstract = {BACKGROUND: Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD.<br><br>METHODS: In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to anti-VEGF were assigned to four cohorts differing by ixo-vec dose (2&#xa0;&#xd7;&#xa0;10[11] vs 6&#xa0;&#xd7;&#xa0;10[11] vector genomes (vg/eye)) and prophylactic steroids (oral prednisone vs topical difluprednate). The primary outcome was the type, severity, and incidence of ocular and systemic adverse events (AEs); secondary endpoints included vision, central subfield thickness (CST), and the number of supplemental injections. This study was registered with ClinicalTrials.gov, NCT03748784.<br><br>FINDINGS: Thirty patients with nAMD were enrolled between November 14, 2018 and June 30, 2020&#xa0;at nine study sites in the United States. No systemic ixo-vec related AEs were noted. Across both dose groups the most common adverse event was anterior chamber cell, which was reported in 11 participants in the 6&#xa0;&#xd7;&#xa0;10[11] dose group and in 7 participants in the 2&#xa0;&#xd7;&#xa0;10[11] dose group; intraocular inflammation was responsive to topical corticosteroids, with no anterior chamber cells or vitreous cells observed in 2&#xa0;&#xd7;&#xa0;10[11] vg/eye patients at the end of the study. Vision and CST remained stable throughout two years with annualised anti-VEGF injections reduced by 80% (10.0 mean annualised anti-VEGF injections to 1.9) in 2&#xa0;&#xd7;&#xa0;10[11] vg/eye and 98% (9.8 mean annualised anti-VEGF injections to 0.2) in 6&#xa0;&#xd7;&#xa0;10[11] vg/eye cohorts.<br><br>INTERPRETATION: Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections. A single administration of an in-office gene therapy, with vectorised protein with an already established clinical benefit, has the potential to revolutionise the management of common ocular disorders requiring ongoing, frequent therapeutic interventions.<br><br>FUNDING: Adverum Biotechnologies.},
}
@article {pmid38151648,
year = {2024},
author = {Jun, JH and Kim, JS and Palomera, LF and Jo, DG},
title = {Dysregulation of histone deacetylases in ocular diseases.},
journal = {Archives of pharmacal research},
volume = {47},
number = {1},
pages = {20-39},
pmid = {38151648},
issn = {1976-3786},
support = {NRF-2019R1A2C3011422//National Research Foundation of Korea/ ; NRF-2019R1A5A2027340//National Research Foundation of Korea/ ; 20210633//Ministry of Oceans and Fisheries' R&amp;D project, Korea/ ; },
mesh = {Infant, Newborn ; Humans ; *Diabetic Retinopathy/drug therapy ; Histone Deacetylases/metabolism ; Quality of Life ; *Macular Degeneration ; *Glaucoma/drug therapy ; Histone Deacetylase Inhibitors/pharmacology/therapeutic use/chemistry ; },
abstract = {Ocular diseases are a growing global concern and have a significant impact on the quality of life. Cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy are the most prevalent ocular diseases. Their prevalence and the global market size are also increasing. However, the available pharmacotherapy is currently limited. These diseases share common pathophysiological features, including neovascularization, inflammation, and/or neurodegeneration. Histone deacetylases (HDACs) are a class of enzymes that catalyze the removal of acetyl groups from lysine residues of histone and nonhistone proteins. HDACs are crucial for regulating various cellular processes, such as gene expression, protein stability, localization, and function. They have also been studied in various research fields, including cancer, inflammatory diseases, neurological disorders, and vascular diseases. Our study aimed to investigate the relationship between HDACs and ocular diseases, to identify a new strategy for pharmacotherapy. This review article explores the role of HDACs in ocular diseases, specifically focusing on diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity, as well as optic nerve disorders, such as glaucoma and optic neuropathy. Additionally, we explore the interplay between HDACs and key regulators of fibrosis and angiogenesis, such as TGF-β and VEGF, highlighting the potential of targeting HDAC as novel therapeutic strategies for ocular diseases.},
}
@article {pmid38151242,
year = {2023},
author = {Ye, J and Wu, Y and Pan, J and Cai, S and Cheng, Y and Chu, C and Su, M},
title = {ICG-based laser treatments for ophthalmic diseases: Toward their safe and rapid strategy.},
journal = {Luminescence : the journal of biological and chemical luminescence},
volume = {},
number = {},
pages = {},
doi = {10.1002/bio.4658},
pmid = {38151242},
issn = {1522-7243},
support = {3502Z202371026//Natural Science Foundation of Xiamen Municipality/ ; 32271447//National Natural Science Foundation of China (NSFC)/ ; 81925019//National Natural Science Foundation of China (NSFC)/ ; 81801817//National Natural Science Foundation of China (NSFC)/ ; U1705281//National Natural Science Foundation of China (NSFC)/ ; 2021A1515012541//Guangdong Basic and Applied Basic Research Foundation/ ; JCYJ20210324121801004//Shenzhen Science and Technology Program/ ; 202012631001//National College Student Innovation and Entrepreneurship Training Program/ ; },
abstract = {The eye is a very important organ, and keratitis, corneal neovascularization, floaters, age-related macular degeneration, and other vision problems have seriously affected people's quality of life. Among the ophthalmic treatments, laser photocoagulations have been proposed and have shown therapeutic effects in clinical settings. However, corneal thinning and bleeding lesions induced by laser damage have led to limit its applications. To treat the issues of traditional hyperthermia treatments, photosensitizers [e.g., indocyanine green (ICG)] have been investigated to increase the therapeutic effects of corneal neovascularization and choroidal neovascularization. In the recent study, with the help of ICG, laser-induced nanobubble was proposed to treat vitreous opacities. The developed strategies could enlarge the effect of laser irradiation and reduce the side effects, so as to expand the scope of laser treatments in clinical ophthalmic diseases.},
}
@article {pmid38150770,
year = {2024},
author = {Jiang, Y and Fu, X and Shao, M and Chang, W and Zhang, H and Liu, Z},
title = {Eyedrop delivery of therapeutic proteins with zwitterionic polymers to treat dry age-related macular degeneration.},
journal = {Biomaterials},
volume = {305},
number = {},
pages = {122429},
doi = {10.1016/j.biomaterials.2023.122429},
pmid = {38150770},
issn = {1878-5905},
mesh = {Animals ; Mice ; Humans ; Ophthalmic Solutions/therapeutic use ; Polymers ; *Eye Diseases ; Eye ; *Macular Degeneration/drug therapy ; Drug Delivery Systems ; },
abstract = {In clinics, therapeutic proteins are commonly used to treat retinal diseases through intraocular injection, the treatment which suffers from rather low patient compliance. Topical administration (e.g. eye-drops) of large molecule drugs remains a major challenge due to the presence of various barriers in the eye. In this study, zwitterion-grafted chitosan (CS-ZW) was developed and then self-assembled with protein therapeutics including adalimumab (ADA) or catalase (CAT) for the treatment of dry age-related macular degeneration (dAMD) via topical eyedrops. Since CS-ZW can cross the mucus layer and open the tight junctions between epithelial cells, their delivered therapeutic proteins can be shuttled across the ocular barriers to reach the diseased site in the fundus. CS-ZW/ADA eyedrops delivering ADA to bind TNF-α in the fundus achieved a similar therapeutic effect to intravitreal ADA injection in a mouse dAMD model. In addition, the therapeutic effect was further improved by combining eyedrop formulations of CS-ZW/ADA and CS-ZW/CAT, the latter of which can clear reactive oxygen species (ROS) in the lesion to further assist dAMD treatment. Our work provides a simple and effective delivery vehicle that can non-invasively treat fundus diseases such as dAMD, showing potential advantages in reducing side effects associated with intraocular injection and improving patient compliance.},
}
@article {pmid38146880,
year = {2024},
author = {Samanta, A and Alsoudi, AF and Rahimy, E and Chhablani, J and Weng, CY},
title = {Imaging Modalities for Dry Macular Degeneration.},
journal = {International ophthalmology clinics},
volume = {64},
number = {1},
pages = {35-55},
pmid = {38146880},
issn = {1536-9617},
mesh = {Humans ; *Geographic Atrophy ; *Macular Degeneration/diagnostic imaging ; Tomography, Optical Coherence ; },
}
@article {pmid38146879,
year = {2024},
author = {Giacalone, JC and Parkinson, DH and Balikov, DA and Rao, RC},
title = {AMD and Stem Cell-Based Therapies.},
journal = {International ophthalmology clinics},
volume = {64},
number = {1},
pages = {21-33},
pmid = {38146879},
issn = {1536-9617},
support = {P30 CA046592/CA/NCI NIH HHS/United States ; P30 EY007003/EY/NEI NIH HHS/United States ; R01 EY030989/EY/NEI NIH HHS/United States ; T32 GM007863/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Stem Cell Transplantation ; *Retinal Pigment Epithelium ; },
abstract = {Age-related macular degeneration (AMD) is a prevalent and complex disease leading to severe vision loss. Stem cells offer promising prospects for AMD treatment as they can be differentiated into critical retinal cell types that could replace lost host retinal cells or provide trophic support to promote host retinal cell survival. However, challenges such as immune rejection, concerns regarding tumorigenicity, and genomic integrity must be addressed. Clinical trials with stem cell-derived retinal pigment epithelial cells have shown preliminary safety in treating dry AMD, but improvements in manufacturing and surgical techniques cell delivery are needed. Late-stage AMD poses additional hurdles, possibly requiring multi-layered grafts. Advancements in automation technologies and gene correction strategies show potential to enhance iPSC-based therapies. Stem cell-based treatments offer hope for AMD management, but further research and optimization are essential for successful clinical implementation.},
}
@article {pmid38145794,
year = {2024},
author = {Zhao, Q and Lai, K},
title = {Role of immune inflammation regulated by macrophage in the pathogenesis of age-related macular degeneration.},
journal = {Experimental eye research},
volume = {239},
number = {},
pages = {109770},
doi = {10.1016/j.exer.2023.109770},
pmid = {38145794},
issn = {1096-0007},
mesh = {Humans ; *Macular Degeneration/pathology ; Macrophages/pathology ; Inflammation/pathology ; Microglia/pathology ; },
abstract = {Age-related macular degeneration (AMD) can lead to irreversible impairment of visual function, and the number of patients with AMD has been increasing globally. The immunoinflammatory theory is an important pathogenic mechanism of AMD, with macrophages serving as the primary inflammatory infiltrating cells in AMD lesions. Its powerful immunoinflammatory regulatory function has attracted considerable attention. Herein, we provide an overview of the involvement of macrophage-regulated immunoinflammation in different stages of AMD. Additionally, we summarize novel therapeutic approaches for AMD, focusing on targeting macrophages, such as macrophage/microglia modulators, reduction of macrophage aggregation in the subretinal space, modulation of macrophage effector function, macrophage phenotypic alterations, and novel biomimetic nanocomposites development based on macrophage-associated functional properties. We aimed to provide a basis and reference for the further exploration of AMD pathogenesis, developmental influences, and new therapeutic approaches.},
}
@article {pmid38145781,
year = {2024},
author = {Vincent, M and Lehoux, J and Desmarty, C and Moine, E and Legrand, P and Dorandeu, C and Simon, L and Durand, T and Brabet, P and Crauste, C and Begu, S},
title = {A novel lipophenol quercetin derivative to prevent macular degeneration: Intravenous and oral formulations for preclinical pharmacological evaluation.},
journal = {International journal of pharmaceutics},
volume = {651},
number = {},
pages = {123740},
doi = {10.1016/j.ijpharm.2023.123740},
pmid = {38145781},
issn = {1873-3476},
mesh = {Mice ; Rats ; Animals ; Quercetin/pharmacology/therapeutic use ; Micelles ; *Macular Degeneration/drug therapy/prevention &amp; control ; Oxidation-Reduction ; *Nanocapsules/chemistry ; Retinal Pigment Epithelium ; Oxidative Stress ; },
abstract = {Drugs with properties against oxidative and carbonyl stresses are potential candidates to prevent dry age-related macular degeneration (Dry-AMD) and inherited Stargardt disease (STGD1). Previous studies have demonstrated the capacity of a new lipophenol drug: 3-O-DHA-7-O-isopropyl-quercetin (Q-IP-DHA) to protect ARPE19 and primary rat RPE cells respectively from A2E toxicity and under oxidative and carbonyl stress conditions. In this study, first, a new methodology has been developed to access gram scale of Q-IP-DHA. After classification of the lipophenol as BCS Class IV according to physico-chemical and biopharmaceutical properties, an intravenous formulation with micelles (M) and an oral formulation using lipid nanocapsules (LNC) were developed. M were formed with Kolliphor® HS 15 and saline solution 0.9 % (mean size of 16 nm, drug loading of 95 %). The oral formulation was optimized and successfully allowed the formation of LNC (25 nm, 96 %). The evaluation of the therapeutic potency of Q-IP-DHA was performed after IV administration of micelles loaded with Q-IP-DHA (M-Q-IP-DHA) at 30 mg/kg and after oral administration of LNC loaded with Q-IP-DHA (LNC-Q-IP-DHA) at 100 mg/kg in mice. Results demonstrated photoreceptor protection after induction of retinal degeneration by acute light stress making Q-IP-DHA a promising preventive candidate against dry-AMD and STGD1.},
}
@article {pmid38141059,
year = {2024},
author = {Selvam, A and Shah, S and Singh, SR and Sant, V and Harihar, S and Arora, S and Patel, M and Ong, J and Yadav, S and Ibrahim, MN and Sahel, JA and Vupparaboina, KK and Chhablani, J},
title = {Longitudinal changes in pigment epithelial detachment composition indices (PEDCI): new biomarkers in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {5},
pages = {1489-1498},
pmid = {38141059},
issn = {1435-702X},
support = {P30 EY08098//Eye and Ear Foundation of Pittsburgh/ ; },
mesh = {Humans ; Child, Preschool ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Retrospective Studies ; *Retinal Detachment/diagnosis/drug therapy ; Tomography, Optical Coherence ; *Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To evaluate novel, automated biomarkers, pigment epithelial detachment composition indices (PEDCI) in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy through 24 months.<br><br>METHODS: Retrospective analysis of 37 eyes (34 patients) with PED associated with nAMD receiving as-needed anti-VEGF treatment was performed. Best-corrected visual acuity (BCVA) and optical coherence tomography images were acquired at a treatment-na&#xef;ve baseline and 3-, 6-, 12-, 18-, and 24-month visits. Previously validated automated imaging biomarkers, PEDCI-S (serous), PEDCI-N (neovascular), and PEDCI-F (fibrous) within PEDs were measured. ANOVA analysis and Spearman correlation were performed.<br><br>RESULTS: Mean BCVA (in logMAR) was 0.60&#x2009;&#xb1;&#x2009;0.47, 0.45&#x2009;&#xb1;&#x2009;0.41, 0.49&#x2009;&#xb1;&#x2009;0.49, 0.61&#x2009;&#xb1;&#x2009;0.54, 0.59&#x2009;&#xb1;&#x2009;0.56, and 0.67&#x2009;&#xb1;&#x2009;0.57 at baseline, 3, 6, 12, 18, and 24&#xa0;months respectively. Overall, BCVA showed minimal worsening of 0.07&#x2009;&#xb1;&#x2009;0.54 logMAR (p&#x2009;=&#x2009;0.07). 13.38&#x2009;&#xb1;&#x2009;3.77 anti-VEGF injections were given through 24&#xa0;months. PEDCI-F showed an increase of 0.116, 0.122, 0.036, and 0.006 at months 3, 6, 12, and 18 respectively and a decrease of 0.004 at month 24 (p&#x2009;=&#x2009;0.03); PEDCI-S showed a decrease of 0.064, 0.130, 0.091, 0.092, and 0.095 at months 3, 6, 12, 18, and 24 respectively (p&#x2009;=&#x2009;0.16); PEDCI-N showed a decrease of 0.052 at month 3 and an increase of 0.008, 0.055, 0.086, and 0.099 at months 6, 12, 18, and 24 respectively (p&#x2009;=&#x2009;0.06). BCVA was negatively correlated with PEDCI-F (r&#x2009;=&#x2009;-0.28, p&#x2009;<&#x2009;0.01), and positively correlated with PEDCI-N (r&#x2009;=&#x2009;0.28, p&#x2009;<&#x2009;0.01) and PEDCI-S (r&#x2009;=&#x2009;0.15, p&#x2009;=&#x2009;0.03).<br><br>CONCLUSION: Longitudinal analysis of PEDCI supports their utility as biomarkers that characterize treatment related effects by quantifying the relative composition of PEDs.},
}
@article {pmid38140030,
year = {2023},
author = {Jansook, P and Soe, HMSH and Asasutjarit, R and Tun, T and Hnin, HM and Maw, PD and Watchararot, T and Loftsson, T},
title = {Celecoxib/Cyclodextrin Eye Drop Microsuspensions: Evaluation of In Vitro Cytotoxicity and Anti-VEGF Efficacy for Retinal Diseases.},
journal = {Pharmaceutics},
volume = {15},
number = {12},
pages = {},
pmid = {38140030},
issn = {1999-4923},
support = {HEA663300003//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; RES_67_000_3300_000//The Asahi Glass Foundation/ ; //The Second Century Fund (C2F) of the Chulalongkorn University/ ; //The Office of Academic Affairs, Chulalongkorn University./ ; },
abstract = {Celecoxib (CCB), a cyclooxygenase-2 inhibitor, is capable of reducing oxidative stress and vascular endothelial growth factor (VEGF) expression in retinal cells and has been shown to be effective in the treatment of diabetic retinopathy and age-related macular degeneration. However, the ocular bioavailability of CCB is hampered due to its very low aqueous solubility. In a previous study, we developed 0.5% (w/v) aqueous CCB eye drop microsuspensions (MS) containing randomly methylated β-cyclodextrin (RMβCD) or γ-cyclodextrin (γCD) and hyaluronic acid (HA) as ternary CCB/CD/HA nanoaggregates. Both formulations exhibited good physicochemical properties. Therefore, we further investigated their cytotoxicity and efficacy in a human retina cell line in this study. At a CCB concentration of 1000 μg/mL, both CCB/RMβCD and CCB/γCD eye drop MS showed low hemolysis activity (11.1 ± 0.3% or 4.9 ± 0.2%, respectively). They revealed no signs of causing irritation and were nontoxic to retinal pigment epithelial cells. Moreover, the CCB eye drop MS exhibited significant anti-VEGF activity by reducing VEGF mRNA and protein levels compared to CCB suspended in phosphate buffer saline. The ex vivo transscleral diffusion demonstrated that a high quantity of CCB (112.47 ± 37.27 μg/mL) from CCB/γCD eye drop MS was deposited in the porcine sclera. Our new findings suggest that CCB/CD eye drop MS could be safely delivered to the ocular tissues and demonstrate promising eye drop formulations for retinal disease treatment.},
}
@article {pmid38139861,
year = {2023},
author = {Tolentino, MJ and Tolentino, AJ and Tolentino, EM and Krishnan, A and Genead, MA},
title = {Sialic Acid Mimetic Microglial Sialic Acid-Binding Immunoglobulin-like Lectin Agonism: Potential to Restore Retinal Homeostasis and Regain Visual Function in Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {12},
pages = {},
pmid = {38139861},
issn = {1424-8247},
support = {No grant number//University of Central Florida/ ; No grant number//Tolentino Eye Research Foundation/ ; No grant number//Aviceda Therapeutics/ ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of visual loss and dysfunction worldwide, is a disease initiated by genetic polymorphisms that impair the negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of Siglec-mediated glyco-immune checkpoint parainflammatory and inflammatory homeostasis as the main determinant for the vision impairing complications of macular degeneration. The effect of altered glycosylation on microglial maintained retinal para-inflammatory homeostasis and eventual recruitment and polarization of peripheral blood monocyte-derived macrophages (PBMDMs) into the retina can explain the phenotypic variability seen in this clinically heterogenous disease. Restoring glyco-immune checkpoint control with a sialic acid mimetic agonist targeting microglial/macrophage Siglecs to regain retinal para-inflammatory and inflammatory homeostasis is a promising therapeutic that could halt the progression of and improve visual function in all stages of macular degeneration.},
}
@article {pmid38139223,
year = {2023},
author = {Goo, H and Lee, MY and Lee, YJ and Lee, S and Ahn, JC and Hong, N},
title = {Multi-Wavelength Photobiomodulation Ameliorates Sodium Iodate-Induced Age-Related Macular Degeneration in Rats.},
journal = {International journal of molecular sciences},
volume = {24},
number = {24},
pages = {},
pmid = {38139223},
issn = {1422-0067},
support = {S3321436//Ministry of SMEs and Startups(MSS, Korea)/ ; NRF-2020R1A6A1A03043283//Ministry of Education/ ; NRF-2023K1A4A3A02057280//Ministry of Science and ICT/ ; RS-2023-00220408//Ministry of Science and ICT/ ; RS-2023-00248384//Ministry of Education/ ; },
mesh = {Animals ; Rats ; *Low-Level Light Therapy ; *Wet Macular Degeneration ; Iodates/toxicity ; Retina ; },
abstract = {Age-related macular degeneration (AMD) is a global health challenge. AMD causes visual impairment and blindness, particularly in older individuals. This multifaceted disease progresses through various stages, from asymptomatic dry to advanced wet AMD, driven by various factors including inflammation and oxidative stress. Current treatments are effective mainly for wet AMD; the therapeutic options for dry AMD are limited. Photobiomodulation (PBM) using low-energy light in the red-to-near-infrared range is a promising treatment for retinal diseases. This study investigated the effects of multi-wavelength PBM (680, 780, and 830 nm) on sodium iodate-induced oxidatively damaged retinal tissue. In an in vivo rat model of AMD induced by sodium iodate, multi-wavelength PBM effectively protected the retinal layers, reduced retinal apoptosis, and prevented rod bipolar cell depletion. Furthermore, PBM inhibited photoreceptor degeneration and reduced retinal pigment epithelium toxicity. These results suggest that multi-wavelength PBM may be a useful therapeutic strategy for AMD, mitigating oxidative stress, preserving retinal integrity, and preventing apoptosis.},
}
@article {pmid38139215,
year = {2023},
author = {Zinflou, C and Rochette, PJ},
title = {Indenopyrene and Blue-Light Co-Exposure Impairs the Tightly Controlled Activation of Xenobiotic Metabolism in Retinal Pigment Epithelial Cells: A Mechanism for Synergistic Toxicity.},
journal = {International journal of molecular sciences},
volume = {24},
number = {24},
pages = {},
pmid = {38139215},
issn = {1422-0067},
support = {MOP-133719/CAPMC/CIHR/Canada ; },
mesh = {Humans ; *Xenobiotics/toxicity/metabolism ; *Retinal Pigment Epithelium/metabolism ; Retina/metabolism ; Reactive Oxygen Species/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; Oxidative Stress ; },
abstract = {High energy visible (HEV) blue light is an increasing source of concern for visual health. Polycyclic aromatic hydrocarbons (PAH), a group of compounds found in high concentrations in smokers and polluted environments, accumulate in the retinal pigment epithelium (RPE). HEV absorption by indeno [1,2,3-cd]pyrene (IcdP), a common PAH, synergizes their toxicities and promotes degenerative changes in RPE cells comparable to the ones observed in age-related macular degeneration. In this study, we decipher the processes underlying IcdP and HEV synergic toxicity in human RPE cells. We found that IcdP-HEV toxicity is caused by the loss of the tight coupling between the two metabolic phases ensuring IcdP efficient detoxification. Indeed, IcdP/HEV co-exposure induces an overactivation of key actors in phase I metabolism. IcdP/HEV interaction is also associated with a downregulation of proteins involved in phase II. Our data thus indicate that phase II is hindered in response to co-exposure and that it is insufficient to sustain the enhanced phase I induction. This is reflected by an accelerated production of endogenous reactive oxygen species (ROS) and an increased accumulation of IcdP-related bulky DNA damage. Our work raises the prospect that lifestyle and environmental pollution may be significant modulators of HEV toxicity in the retina.},
}
@article {pmid38137963,
year = {2023},
author = {Onwuka, O and Saddemi, JL and Akkan Aydoğmuş, FS and Lasalle, CC and Ramsey, DJ},
title = {Correction: Onwuka et al. Consequences of Real-World Surveillance of Fellow Eyes in Neovascular Age-Related Macular Degeneration. Life 2023, 13, 385.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
pmid = {38137963},
issn = {2075-1729},
abstract = {Text Correction [...].},
}
@article {pmid38137838,
year = {2023},
author = {Manikandan, SK and Logan, A and Cerrada-Gimenez, M and Fitzhenry, L and Coffey, L and Kaja, S and Rani, S},
title = {Immune System, Inflammation and Autoantigens in Wet Age-Related Macular Degeneration: Pathological Significance and Therapeutic Importance.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
pmid = {38137838},
issn = {2075-1729},
support = {EPSPG/2021/147//Irish Research Council/ ; },
abstract = {Wet age-related macular degeneration (wAMD) is a chronic inflammation-associated neurodegenerative disease affecting the posterior part of the eye in the aging population. Aging results in the reduced functionality of cells and tissues, including the cells of the retina. Initiators of a chronic inflammatory and pathologic state in wAMD may be a result of the accumulation of inevitable metabolic injuries associated with the maintenance of tissue homeostasis from a young age to over 50. Apart from this, risk factors like smoking, genetic predisposition, and failure to repair the injuries that occur, alongside attempts to rescue the hypoxic outer retina may also contribute to the pathogenesis. Aging of the immune system (immunosenescence) and a compromised outer blood retinal barrier (BRB) result in the exposure of the privileged milieu of the retina to the systemic immune system, further increasing the severity of the disease. When immune-privileged sites like the retina are under pathological stress, certain age- and disease-related conditions may necessitate assistance from cells distant from the resident ones to help restore the functionality of the tissue. As a necessary part of tissue repair, inflammation is a major response to disease and recruits immune cells to the site of damage. We suspect that the specific reparative inflammatory responses are controlled by an autoantigen-T cell-mediated mechanism, a process that may be hindered in wAMD.},
}
@article {pmid38137797,
year = {2023},
author = {Krytkowska, E and Olejnik-Wojciechowska, J and Grabowicz, A and Safranow, K and Machalińska, A},
title = {Association between Subretinal Drusenoid Deposits and Age-Related Macular Degeneration in Multimodal Retinal Imaging.},
journal = {Journal of clinical medicine},
volume = {12},
number = {24},
pages = {},
pmid = {38137797},
issn = {2077-0383},
abstract = {Multimodal retinal imaging enables the detection of subretinal drusenoid deposits (SDD) with significantly greater accuracy compared to fundus photography. The study aimed to analyze a relationship between the presence of SDD, the clinical picture of AMD, and disease progression in a 3 year follow-up. A total of 602 eyes of 339 patients with a diagnosis of AMD, of which 121 (55%) had SDD confirmed in multimodal retinal imaging, were enrolled in the study. SDD was related to a more advanced stage of AMD (p = 0.008), especially with the presence of geographic atrophy (OR = 4.11, 95% CI 2.02-8.38, p < 0.001). Eyes with SDD presented significantly lower choroidal and retinal thickness (ATC: 210.5 μm, CRT: 277 μm, respectively) and volume (AVC: 0.17 mm[3], CRV: 8.29 mm[3], p < 0.001, respectively) compared to SDD-negative eyes (ATC: 203 μm, CRT: 277 μm; AVC: 7.08 mm[3], 8.54 mm[3], p < 0.001). Accordingly, the prevalence of pachychoroids and pachyvessels was significantly lower in the SDD present group than in eyes without SDD (p = 0.004; p = 0.04, respectively). Neither demographic factors, lipid profile, genetic predisposition, systemic vascular disease comorbidities, nor parameters of retinal vessels were affected by the presence of SDD. We found no effect of SDD presence on AMD progression (p = 0.12). The presence of SDD appeared to be related to local rather than systemic factors.},
}
@article {pmid38137479,
year = {2023},
author = {Donato, L and Mordà, D and Scimone, C and Alibrandi, S and D'Angelo, R and Sidoti, A},
title = {Bridging Retinal and Cerebral Neurodegeneration: A Focus on Crosslinks between Alzheimer-Perusini's Disease and Retinal Dystrophies.},
journal = {Biomedicines},
volume = {11},
number = {12},
pages = {},
pmid = {38137479},
issn = {2227-9059},
abstract = {In the early stages of Alzheimer-Perusini's disease (AD), individuals often experience vision-related issues such as color vision impairment, reduced contrast sensitivity, and visual acuity problems. As the disease progresses, there is a connection with glaucoma and age-related macular degeneration (AMD) leading to retinal cell death. The retina's involvement suggests a link with the hippocampus, where most AD forms start. A thinning of the retinal nerve fiber layer (RNFL) due to the loss of retinal ganglion cells (RGCs) is seen as a potential AD diagnostic marker using electroretinography (ERG) and optical coherence tomography (OCT). Amyloid beta fragments (Aβ), found in the eye's vitreous and aqueous humor, are also present in the cerebrospinal fluid (CSF) and accumulate in the retina. Aβ is known to cause tau hyperphosphorylation, leading to its buildup in various retinal layers. However, diseases like AD are now seen as mixed proteinopathies, with deposits of the prion protein (PrP) and α-synuclein found in affected brains and retinas. Glial cells, especially microglial cells, play a crucial role in these diseases, maintaining immunoproteostasis. Studies have shown similarities between retinal and brain microglia in terms of transcription factor expression and morphotypes. All these findings constitute a good start to achieving better comprehension of neurodegeneration in both the eye and the brain. New insights will be able to bring the scientific community closer to specific disease-modifying therapies.},
}
@article {pmid38137442,
year = {2023},
author = {Finocchio, L and Zeppieri, M and Gabai, A and Toneatto, G and Spadea, L and Salati, C},
title = {Recent Developments in Gene Therapy for Neovascular Age-Related Macular Degeneration: A Review.},
journal = {Biomedicines},
volume = {11},
number = {12},
pages = {},
pmid = {38137442},
issn = {2227-9059},
abstract = {Age-related macular degeneration (AMD) is a complex and multifactorial disease and a leading cause of irreversible blindness in the elderly population. The anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management and prognosis of neovascular AMD (nAMD) and is currently the standard of care for this disease. However, patients are required to receive repeated injections, imposing substantial social and economic burdens. The implementation of gene therapy methods to achieve sustained delivery of various therapeutic proteins holds the promise of a single treatment that could ameliorate the treatment challenges associated with chronic intravitreal therapy, and potentially improve visual outcomes. Several early-phase trials are currently underway, evaluating the safety and efficacy of gene therapy for nAMD; however, areas of controversy persist, including the therapeutic target, route of administration, and potential safety issues. In this review, we assess the evolution of gene therapy for nAMD and summarize several preclinical and early-stage clinical trials, exploring challenges and future directions.},
}
@article {pmid38137345,
year = {2023},
author = {Ameri, H and Kesavamoorthy, N and Bruce, DN},
title = {Frequency and Pattern of Worldwide Ocular Gene Therapy Clinical Trials up to 2022.},
journal = {Biomedicines},
volume = {11},
number = {12},
pages = {},
pmid = {38137345},
issn = {2227-9059},
support = {Unrestricted Grant to the Department of Ophthalmology//Research to Prevent Blindness/ ; },
abstract = {The purpose of this study is to describe worldwide gene therapy clinical trials aimed at treating ophthalmic disorders. Information regarding all worldwide clinical trials was collected through 15 different sources, including ClinicalTrials.gov. There were 159 gene therapy clinical trials on ophthalmic diseases up until 2022. Phase 1/2 trials had the highest frequency (50-32%), followed by phase 2 (33-21%); 107 trials (67%) were conducted in a single country, and 50 trials (31%) were multinational. Overall, the USA was the site of 113 (71%) single or multinational trials. Of the trials, 153 (96%) targeted retina and optic nerve disorders, 3 (2%) glaucoma, 2 (1%) uveitis, and 1 (1%) cornea; 104 trials (65%) employed gene augmentation using viral vectors, and the remaining employed other methods such as inhibitory RNA (18-11%) and cell-based gene therapy using encapsulated cell technology (18-11%). For gene augmentation trials, adeno-associated virus was used for transgene delivery in 87% of cases. The most common conditions targeted by gene augmentation included inherited retinal (74%) and age-related macular degeneration (wet, 14%; dry, 7%). Overall, a large number of gene therapy clinical trials have been conducted in the eye, and so far, one has led to regulatory approval.},
}
@article {pmid38136248,
year = {2023},
author = {Biswal, MR and Paulson, RJ and Vichare, R and Lewin, AS},
title = {Buspirone Enhances Cell Survival and Preserves Structural Integrity during Oxidative Injury to the Retinal Pigment Epithelium.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {12},
pages = {},
pmid = {38136248},
issn = {2076-3921},
support = {R00 EY027013/EY/NEI NIH HHS/United States ; R01 EY033415/EY/NEI NIH HHS/United States ; R41 EY034735/EY/NEI NIH HHS/United States ; R00EY027013, R01EY033415/NH/NIH HHS/United States ; },
abstract = {Chronic oxidative stress impairs the normal functioning of the retinal pigment epithelium (RPE), leading to atrophy of this cell layer in cases of advance age-related macular degeneration (AMD). The purpose of our study was to determine if buspirone, a partial serotonin 1A (5-HT1A) receptor agonist, protected against oxidative stress-induced changes in the RPE. We exposed differentiated human ARPE-19 cells to paraquat to induce oxidative damage in culture, and utilized a mouse model with sodium iodate (NaIO3)-induced oxidative injury to evaluate the effect of buspirone. To investigate buspirone's effect on protective gene expression, we performed RT-PCR. Cellular toxicities and junctional abnormalities due to paraquat induction in ARPE-19 cells and buspirone's impact were assessed via WST-1 assays and ZO-1 immunostaining. We used spectral-domain optical coherence tomography (SD-OCT) and ZO-1 immunostaining of RPE/choroid for structural analysis. WST-1 assays showed dose-dependent protection of viability in buspirone-treated ARPE-19 cells in culture and preservation of RPE junctional integrity under oxidative stress conditions. In the NaIO3 model, daily intraperitoneal injection (i.p.) of buspirone (30 mg/kg) for 12 days improved the survival of photoreceptors compared to those of vehicle-treated eyes. ZO-1-stained RPE flat-mounts revealed the structural preservation of RPE from oxidative damage in buspirone-treated mice, as well as in buspirone-induced Nqo1, Cat, Sqstm1, Gstm1, and Sod2 genes in the RPE/choroid compared to untreated eyes. Since oxidative stress is implicated in the pathogenesis AMD, repurposing buspirone, which is currently approved for the treatment of anxiety, might be useful in treating or preventing dry AMD.},
}
@article {pmid38136230,
year = {2023},
author = {Różanowska, MB},
title = {Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {12},
pages = {},
pmid = {38136230},
issn = {2076-3921},
abstract = {Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage, which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested to be more sensitive and specific for imaging spectral characteristics of lipofuscin fluorescence.},
}
@article {pmid38136192,
year = {2023},
author = {Fietz, A and Corsi, F and Hurst, J and Schnichels, S},
title = {Blue Light Damage and p53: Unravelling the Role of p53 in Oxidative-Stress-Induced Retinal Apoptosis.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {12},
pages = {},
pmid = {38136192},
issn = {2076-3921},
abstract = {In the digital age, the widespread presence of electronic devices has exposed humans to an exceptional amount of blue light (BL) emitted from screens, LEDs, and other sources. Studies have shown that prolonged exposure to BL could have harmful effects on the visual system and circadian rhythm regulation. BL is known to induce oxidative stress, leading to DNA damage. Emerging research indicates that BL may also induce cell death pathways that involve the tumor-suppressor protein p53. Activated p53 acts as a transcription factor to regulate the expression of genes involved in cell cycle arrest, DNA repair, and apoptosis. This study aimed to explore the implication of p53 in BL-caused retinal damage, shedding light on the potential mechanisms of oxidative-stress-induced retinal diseases. BL-exposed porcine retinal cultures demonstrated increased p53- and caspase-mediated apoptosis, depending on exposure duration. Direct inhibition of p53 via pifithrin α resulted in the prevention of retinal cell death. These findings raise concerns about the long-term consequences of the current daily BL exposure and its potential involvement in various pathological conditions, including oxidative-stress-based retinal diseases like age-related macular degeneration. In addition, this study paves the way for the development of novel therapeutic approaches for oxidative-stress-based retinal diseases.},
}
@article {pmid38136017,
year = {2023},
author = {Tabuchi, H and Yamauchi, T and Nagasawa, T and Deguchi, H and Tanabe, M and Tanaka, H and Yasukawa, T},
title = {Revolutionizing Patient Monitoring in Age-Related Macular Degeneration: A Comparative Study on the Necessity and Efficiency of the AMD VIEWER.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {10},
number = {12},
pages = {},
pmid = {38136017},
issn = {2306-5354},
abstract = {(1) Background: Age-related Macular Degeneration (AMD) is a critical condition leading to blindness, necessitating lifelong clinic visits for management, albeit with existing challenges in monitoring its long-term progression. This study introduced and assessed an innovative tool, the AMD long-term Information Viewer (AMD VIEWER), designed to offer a comprehensive display of crucial medical data-including visual acuity, central retinal thickness, macular volume, vitreous injection treatment history, and Optical Coherent Tomography (OCT) images-across an individual eye's entire treatment course. (2) Methods: By analyzing visit frequencies of patients with a history of invasive AMD treatment, a comparative examination between a Dropout group and an Active group underscored the clinical importance of regular visits, particularly highlighting better treatment outcomes and maintained visual acuity in the Active group. (3) Results: The efficiency of AMD VIEWER was proven by comparing it to manual data input by optometrists, showing significantly faster data display with no errors, unlike the time-consuming and error-prone manual entries. Furthermore, an elicited Net Promoter Score (NPS) of 70 from 10 ophthalmologists strongly endorsed AMD VIEWER's practical utility. (4) Conclusions: This study underscores the importance of regular clinic visits for AMD patients. It suggests the AMD VIEWER as an effective tool for improving treatment data management and display.},
}
@article {pmid38135238,
year = {2024},
author = {Teo, KYC and Zhao, J and Ibrahim, FI and Fenner, B and Chakravarthy, U and Cheung, CMG},
title = {Features Associated With Vision in Eyes With Subfoveal Fibrosis From Neovascular Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {261},
number = {},
pages = {121-131},
doi = {10.1016/j.ajo.2023.12.011},
pmid = {38135238},
issn = {1879-1891},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Case-Control Studies ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Fibrosis ; Tomography, Optical Coherence/methods ; *Macular Degeneration ; Fluorescein Angiography ; *Wet Macular Degeneration/complications/diagnosis ; },
abstract = {PURPOSE: To report the characteristics and correlation of visual acuity in eyes treated for neovascular age-related macular degeneration (nAMD) and developed fibrosis.<br><br>DESIGN: Case-control study.<br><br>METHODS: Three hundred fifty-six treatment-naive nAMD eyes that were treated for 12 months were included. Fibrosis was defined as present if well-defined hyperreflective material (HRM) were present between the neurosensory retina and the Bruch membrane on optical coherence tomography (OCT) that correlated with well-defined regions of yellowish pallor on fundus photography and/or staining on fluorescence angiography. OCT features of subfoveal fibrosis and the overlying retina were correlated with visual acuity at month 12.<br><br>RESULTS: Sixty-three eyes (20.3%) developed incident fibrosis at month 12. Compared with eyes that did not develop fibrosis, these eyes had lower baseline vision (49 vs 54 letters, P = .02) and more of them had type 2 macular neovascularization (15.0 vs 8.8%, P = .03), larger lesion area (29.6 vs 15.1 mm[2], P = .02), and subretinal hemorrhage &#x2265;4 disc diameters (44.4% vs 19.8%, P < .01). Visual acuity was worse in the incident fibrosis compared with the group that never developed fibrosis by month 12. (-1.4&#xb1;17.1 versus +6.0&#xb1;17.4 letters, P < .01). In 83 eyes that had subfoveal fibrosis, better vision was associated with intact ellipsoid zone-external limiting membrane complex (&#x3b2; coefficient 29.4, 95% CI 14.2-44.6, P < .01), whereas worse vision was associated with retinal pigment epithelium (RPE)-involving HRM, HRM above the RPE, and width of HRM (&#x3b2; coefficients -25.4 [95% CI -36.3 to -14.6], P < .01; -23.5 [95% CI -39.0 to -7.9], P < .01; and -3.8 [95% CI -7.2 to -0.4], P = .03, respectively).<br><br>CONCLUSION: Although fibrosis is associated with poorer visual outcome, preservation of external limiting membrane and level of fibrosis relative to the RPE are associated with visual outcomes.},
}
@article {pmid38134207,
year = {2023},
author = {Pauleikhoff, D and Gunnemann, ML and Ziegler, M and Heimes-Bussmann, B and Bormann, E and Bachmeier, I and Yu, S and Garcia Armendariz, B and Pauleikhoff, L},
title = {Morphological changes of macular neovascularization during long-term anti-VEGF-therapy in neovascular age-related macular degeneration.},
journal = {PloS one},
volume = {18},
number = {12},
pages = {e0288861},
pmid = {38134207},
issn = {1932-6203},
mesh = {Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Retrospective Studies ; Fluorescein Angiography ; *Choroidal Neovascularization/diagnostic imaging/drug therapy ; Intravitreal Injections ; *Macular Degeneration/diagnostic imaging/drug therapy ; Tomography, Optical Coherence ; *Wet Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: To analyze the morphological changes of macular neovascularization (MNV) in exudative neovascular age-related macular degeneration under long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy in a retrospective cohort study.<br><br>METHODS AND PATIENTS: We evaluated 143 nAMD eyes of 94 patients (31 male, 63 female; initial age 55-97 y, mean age 75.9 &#xb1; 7.5 y), who started anti-VEGF therapy (IVAN pro re nata (PRN) protocol) between 2009-2018 and received ongoing therapy until the last recorded visit (mean follow-up 5.3 &#xb1; 2.9 y, range 1-14 y). The mean total number of injections was 33.3 &#xb1; 19.8 with 7.0 &#xb1; 2.3 injections/year. MNV size and, if present, associated complete retinal pigment epithelium (RPE) and outer retina atrophy (cRORA) size were measured on optical coherence tomography (OCT) volume scans at the initial visit and for each year of follow-up. MNV and cRORA were identified on B-scans and their respective borders were manually transposed onto the en-face near infrared image and measured in mm2.<br><br>RESULTS: MNV enlarged through follow-up, with a mean growth rate of 1.24 mm2 / year. The mean growth in MNV size was independent of initial MNV size, age, gender, MNV subtypes or number of injections per year. Nevertheless, a great interindividual variation in size and growth was observed. cRORA developed in association with increasing MNV size and its incidence increased linearly over follow-up. cRORA lesions also showed continuous growth by a rate of 1.22 mm2 / year.<br><br>CONCLUSIONS: Despite frequent long-term anti-VEGF therapy, we observed ongoing MNV growth. This is consistent with the concept that the development of MNV may be a physiological biological repair mechanism to preserve RPE and photoreceptor function, provided hyperpermeability and fluid exudation are controlled. Whether recurring low VEGF levels or other factors are responsible for MNV growth remains controversial.},
}
@article {pmid38133943,
year = {2024},
author = {Palmieri, F and Younis, S and Bedan Hamoud, A and Fabozzi, L},
title = {Uveitis Following Intravitreal Injections of Faricimab: A Case Report.},
journal = {Ocular immunology and inflammation},
volume = {32},
number = {8},
pages = {1873-1877},
doi = {10.1080/09273948.2023.2293925},
pmid = {38133943},
issn = {1744-5078},
mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects/administration &amp; dosage ; Angiopoietin-2 ; Fluorescein Angiography ; Intraocular Pressure/drug effects ; *Intravitreal Injections ; Retrospective Studies ; Tomography, Optical Coherence ; *Uveitis/chemically induced/diagnosis/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; },
abstract = {PURPOSE: Faricimab, a novel pharmaceutical agent targeting both angiopoietin-2 and vascular endothelial growth factor-A pathways, has gained approval for treating neovascular age-related macular degeneration and diabetic macular oedema. While clinical trials have demonstrated its favorable safety profile, this research presents two cases of hypertensive uveitis following intravitreal Faricimab injections.<br><br>METHODS: Medical history, clinical findings and multimodal images were retrospectively collected.<br><br>RESULTS: The patients experienced elevated intraocular pressure, mutton-fat keratic precipitates, anterior and posterior segment inflammation shortly after faricimab administration.<br><br>CONCLUSIONS: These cases prompt further investigation into the potential risk of uveitis associated with faricimab and underscore the importance of continued monitoring and research to elucidate its real-world safety profile.},
}
@article {pmid38132360,
year = {2023},
author = {Karachaliou, CE and Livaniou, E},
title = {Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives.},
journal = {Biology},
volume = {12},
number = {12},
pages = {},
pmid = {38132360},
issn = {2079-7737},
abstract = {Humanin is a 24-mer peptide first reported in the early 2000s as a new neuroprotective/cytoprotective factor rescuing neuronal cells from death induced by various Alzheimer's disease-associated insults. Nowadays it is known that humanin belongs to the novel class of the so-called mitochondrial-derived peptides (which are encoded by mitochondrial DNA) and has been shown to exert beneficial cytoprotective effects in a series of in vitro and/or in vivo experimental models of human diseases, including not only neurodegenerative disorders but other human diseases as well (e.g., age-related macular degeneration, cardiovascular diseases, or diabetes mellitus). This review article is focused on the presentation of recent in vitro and in vivo research results associated with the neuroprotective action of humanin as well as of various, mainly synthetic, analogues of the peptide; moreover, the main mode(s)/mechanism(s) through which humanin and humanin analogues may exert in vitro and in vivo regarding neuroprotection have been reported. The prospects of humanin and humanin analogues to be further investigated in the frame of future research endeavors against neurodegenerative/neural diseases have also been briefly discussed.},
}
@article {pmid38132220,
year = {2023},
author = {Cheng, AMS and Chalam, KV and Brar, VS and Yang, DTY and Bhatt, J and Banoub, RG and Gupta, SK},
title = {Recent Advances in Imaging Macular Atrophy for Late-Stage Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {24},
pages = {},
pmid = {38132220},
issn = {2075-4418},
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD eventually results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicts advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus photography; dye-based angiography; fundus autofluorescence (FAF); near-infrared reflectance (NIR); optical coherence tomography (OCT); and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. These evolving diverse imaging modalities optimize detection of pathologic anatomy and measurement of visual function; they may also contribute to the understanding of underlying mechanistic pathways, particularly the underlying MA changes in late AMD.},
}
@article {pmid38131550,
year = {2024},
author = {Archambault, SD and Nichols, MM and McCullum, JC and Zhang, Y and Steinberger, EE and Ramsey, DJ},
title = {Patient adherence to therapy after switch to aflibercept from bevacizumab or ranibizumab for treatment-refractory neovascular age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 1},
pages = {S101-S105},
pmid = {38131550},
issn = {1998-3689},
mesh = {Humans ; *Ranibizumab ; Bevacizumab ; Angiogenesis Inhibitors ; Retrospective Studies ; Cross-Sectional Studies ; Treatment Outcome ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins/therapeutic use ; Intravitreal Injections ; *Macular Degeneration ; Patient Compliance ; },
abstract = {PURPOSE: Clinical trials have demonstrated that switching patients from intravitreal bevacizumab (IVB) or ranibizumab (IVR) to aflibercept (IVA) for treatment-refractory neovascular age-related macular degeneration (nAMD) can decrease the injection frequency. This study evaluated whether there was a difference in the rate of injections or nonadherent events after switching therapies.<br><br>METHODS: The study comprised a retrospective, cross-sectional analysis of patients treated for nAMD from 2010 to 2018 who received &#x2265;3 intravitreal injections of IVB/IVR prior to switching to IVA because of treatment-refractory nAMD. The treatment index, outcomes, and adherence to treatment were compared between both treatment regimens.<br><br>RESULTS: Sixty-two patients (67 eyes) met inclusion criteria. There was no change in the treatment index (0.65 versus 0.66, P = 0.650) or the number of nonadherent events (33 versus 36, P = 0.760) after the switch from IVB/IVR to IVA. Central macular thickness (CMT) increased 7.7%&#xb1;13.8% in eyes that had a nonadherent event (283&#xb1;69 &#xb5;m to 304&#xb1;75 &#xb5;m after resuming care, P = 0.039). There was no short-term impact on visual acuity (VA) for this subset of eyes (0.387&#xb1;0.202 LogMAR versus 0.365&#xb1;0.156 LogMAR, P = 0.636). Patients who had nonadherent events ended the study with similar VA compared with patients who had no treatment lapses (0.370&#xb1;0.616 LogMAR versus 0.337&#xb1;0.638 LogMAR, P = 0.843).<br><br>CONCLUSION: Switching from IVB/ IVR to IVA for treatment-refractory nAMD in a real-world setting does not reduce the treatment index or increase adherence to treatment. Although there were short-term anatomical effects resulting from missed treatments, VA remained stable.},
}
@article {pmid38131539,
year = {2024},
author = {Dabir, S and Mohankumar, A and Khatri, MG and Rajan, M},
title = {Brolucizumab in age-related macular neovascularization (BRAIN study): Efficacy, optical coherence tomography biomarkers, and safety profile.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 1},
pages = {S33-S36},
pmid = {38131539},
issn = {1998-3689},
mesh = {Humans ; Angiogenesis Inhibitors ; Tomography, Optical Coherence/methods ; Retrospective Studies ; *Choroidal Neovascularization/diagnosis/drug therapy ; Intravitreal Injections ; Biomarkers ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {BACKGROUND: Brolucizumab is a new anti-vascular endothelial growth factor (anti-VEGF) in the treatment of neovascular age-related macular degeneration (nAMD) and idiopathic polypoidal choroidal vasculopathy (IPCV).<br><br>MATERIALS AND METHODS: A retrospective, consecutive, interventional study was conducted from a tertiary eye hospital, in which treatment-na&#xef;ve and treatment-switch patients were included. They underwent an intravitreal injection of brolucizumab. The decision to reinject was made based on the presence of fluid on spectral domain optical coherence tomography (SD-OCT) or worsening of vision at follow-up. Outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), fluid (subretinal/intraretinal/sub-retinal pigment epithelium fluid) levels, and OCT biomarkers and safety analysis.<br><br>RESULTS: A total of 59 eyes of 50 patients with a total of 132 intravitreal injections were included. There was a statistically significant improvement (P < 0.05) in BCVA from baseline in logMAR treatment-na&#xef;ve patients (mean BCVA at baseline 0.6 &#xb1; 0.41 and 0.37 &#xb1; 0.56). The mean baseline CST of all patients significantly reduced from 582.92 &#xb1; 233.11 &#xb5;m at baseline to 474.06 &#xb1; 252.89 &#xb5;m at the final treatment visit. Thirty-eight percent of patients showed complete resolution of SHRM after a single injection. The interval between each subsequent injection increased from a mean of 67 to 96 days in treatment-switch patients and from 47 to 151 days in treatment-na&#xef;ve patients.<br><br>CONCLUSION: Brolucizumab promises reduced number of injections with longer treatment intervals.},
}
@article {pmid38131538,
year = {2024},
author = {Narnaware, SH and Bansal, A and Bawankule, PK and Raje, D},
title = {Real-world experience of brolucizumab in nAMD.},
journal = {Indian journal of ophthalmology},
volume = {72},
number = {Suppl 1},
pages = {S27-S32},
pmid = {38131538},
issn = {1998-3689},
mesh = {Humans ; Infant ; Angiogenesis Inhibitors ; *Choroidal Neovascularization/diagnosis/drug therapy ; Intravitreal Injections ; Prospective Studies ; *Retinal Detachment/drug therapy ; Retinal Pigment Epithelium ; Tomography, Optical Coherence/methods ; Visual Acuity ; },
abstract = {PURPOSE: To evaluate real-world outcomes with neovascular age-related macular degeneration (nAMD) in relation to anatomical success, visual outcomes, and safety of intravitreal brolucizumab (IVBr) injection at 1.5 years.<br><br>METHODS: Prospective, randomized, single-center study between December 2020 and December 2022 that included 71 eyes of 62 patients with nAMD, who received IVBr. Patients were divided into three groups, i.e., na&#xef;ve choroidal neovascular membrane (CNVM), switched therapy (st) CNVM, and st polypoidal choroidal vasculopathy (stPCV). They were subdivided into dry, minimal fluid (fluid <50 microns)/pigment epithelial detachment (PED) and persistent fluid (fluid >100 microns)/PED subgroups depending upon the fluid level at the end of 1.5 years. Best-corrected visual acuity (BCVA), central macular thickness (CMT), status of fluid, and number of injections at 1.5 years were evaluated. From the beginning, patients were treated on pro re nata (PRN) basis.<br><br>RESULTS: Of the 71 eyes, 27 eyes (38%) were na&#xef;ve CNVM, 35 eyes (49.3%) were stCNVM, and 9 (12.7%) were stPCV cases. Significant vision improvement after 1.5 years was seen in the stCNVM category (P = 0.001), while CMT reduction was significant in all three groups (P < 0.05). The mean number of injections required in na&#xef;ve CNVM and stCNVM groups was significantly less as compared to the stPCV group (P = 0.017). Further, vision improvement was significant in the "Minimal fluid" subgroup (P = 0.002), while the CMT improvement was significant in the "Minimal fluid" and "Dry" subgroups each with P < 0.0001. No ocular/systemic adverse events including intraocular inflammation (IOI) were noted.<br><br>CONCLUSION: In a real-world scenario, with 203 procedures and 1.5-year follow-up, brolucizumab is found to be efficacious and safe with the need for a lesser number of injections and more interval-free period in the management of na&#xef;ve CNVM, stCNVM, and stPCV patients.},
}
@article {pmid38131161,
year = {2024},
author = {de la Fuente, J and Llorente-González, S and Fernandez-Robredo, P and Hernandez, M and García-Layana, A and Ochoa, I and Recalde, S and , },
title = {Suitability of machine learning for atrophy and fibrosis development in neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {5},
pages = {e831-e841},
doi = {10.1111/aos.16616},
pmid = {38131161},
issn = {1755-3768},
support = {//ISCIII Thematic Network of Cooperative Health Research General Subdirection/ ; //Multiopticas Foundation/ ; PID2021-126718OA-I00//Spanish Ministry of Science and Innovation/ ; //Fulbright Association/ ; //Ramon y Cajal Grant from Spain/ ; RD16/0008/0021//Thematic Network of Cooperative Health Research in Eye Diseases/ ; PI15/01374//FIS Project European Program FEDER/ ; //Gipuzkoa Fellows grant from the Basque Government/ ; },
mesh = {Humans ; *Machine Learning ; *Angiogenesis Inhibitors/therapeutic use ; Male ; *Wet Macular Degeneration/diagnosis/drug therapy ; Female ; *Fibrosis ; *Visual Acuity ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Intravitreal Injections ; Tomography, Optical Coherence/methods ; Atrophy ; Follow-Up Studies ; Aged, 80 and over ; Retrospective Studies ; Ranibizumab/administration &amp; dosage/therapeutic use ; Fluorescein Angiography/methods ; Fundus Oculi ; },
abstract = {PURPOSE: To assess the suitability of machine learning (ML) techniques in predicting the development of fibrosis and atrophy in patients with neovascular age-related macular degeneration (nAMD), receiving anti-VEGF treatment over a 36-month period.<br><br>METHODS: An extensive analysis was conducted on the use of ML to predict fibrosis and atrophy development on nAMD patients at 36&#x2009;months from start of anti-VEGF treatment, using only data from the first 12&#x2009;months. We use data collected according to real-world practice, which includes clinical and genetic factors.<br><br>RESULTS: The ML analysis consistently identified ETDRS as a relevant factor for predicting the development of atrophy and fibrosis, confirming previous statistical analyses. Also, it was shown that genetic variables did not demonstrate statistical relevance in the prediction. Despite the complexity of predicting macular degeneration, our model was able to obtain a balance accuracy of 63% and an AUC of 0.72 when predicting the development of atrophy or fibrosis at 36&#x2009;months.<br><br>CONCLUSION: This study demonstrates the potential of ML techniques in predicting the development of fibrosis and atrophy in nAMD patients receiving long-term anti-VEGF treatment. The findings highlight the importance of clinical factors, particularly ETDRS (early treatment diabetic retinopathy study) visual acuity test, in predicting these outcomes. The lessons learned from this research can guide future ML-based prediction tasks in the field of ophthalmology and contribute to the design of data collection processes.},
}
@article {pmid38129891,
year = {2023},
author = {Shen, T and Lin, R and Hu, C and Yu, D and Ren, C and Li, T and Zhu, M and Wan, Z and Su, T and Wu, Y and Cai, W and Yu, J},
title = {Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
pages = {308},
pmid = {38129891},
issn = {1742-2094},
support = {82000903//Youth Program of National Natural Science Foundation of China/ ; 82101130//Youth Program of National Natural Science Foundation of China/ ; 2022YFC2407005//National Key Research and Development Program of China/ ; YNCR2B003//Clinical Research Project of Shanghai Tenth People's Hospital/ ; },
mesh = {Infant, Newborn ; Humans ; Animals ; Succinic Acid/metabolism ; Eye/metabolism ; *Choroidal Neovascularization/metabolism ; *Retinopathy of Prematurity/metabolism ; Macrophages/metabolism ; Disease Models, Animal ; Retinol-Binding Proteins, Plasma/metabolism ; },
abstract = {Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization.},
}
@article {pmid38126346,
year = {2024},
author = {Feng, J and Xie, F and Wu, Z and Wu, Y},
title = {Age-related macular degeneration and cardiovascular disease in US population: an observational study.},
journal = {Acta cardiologica},
volume = {79},
number = {6},
pages = {665-671},
doi = {10.1080/00015385.2023.2295103},
pmid = {38126346},
issn = {1784-973X},
mesh = {Humans ; Male ; Female ; *Macular Degeneration/epidemiology/diagnosis ; United States/epidemiology ; *Cardiovascular Diseases/epidemiology ; *Nutrition Surveys ; Aged ; Middle Aged ; Incidence ; Risk Factors ; Retrospective Studies ; Risk Assessment/methods ; },
abstract = {BACKGROUND: As far as we know, age-related macular degeneration (AMD) has become one of the predominant causes of visual impairments. Previous studies have revealed that AMD and many cardiovascular diseases (CVDs) share the same pathologic and genotypic factors, making the connection between AMD and CVD a hot topic. However, the conclusions of the available studies on the relationship between them are somewhat divergent.<br><br>METHODS: We screened 5523 eligible participants from the National Health and Nutrition Examination Survey (NHANES) database from 2005 through 2008 for an observational clinical study design. Binary logistic regression modelling was used to estimate the relations between AMD and various CVDs with and without adjustment for demographics, health status, and behaviours related to health.<br><br>RESULTS: Binary logistic regression analyses showed that AMD was able to increase the risk of CVDs in patients both unadjusted and after adjusting for confounding variables.<br><br>CONCLUSIONS: Within this study, preventing the development of AMD might cut down the incidence of several CVDs, in particular, significantly lowering the stroke risk. These findings indicate that interventions to prevent AMD may also help to prevent CVDs. In general, late AMD has a more severe impact on the risk of CVDs compared with early AMD. These results could help clinical ophthalmology and cardiovascular medicine in their clinical education and interventions.},
}
@article {pmid38123670,
year = {2024},
author = {Wijesingha, N and Sivaprasad, S},
title = {Infographic: Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE).},
journal = {Eye (London, England)},
volume = {38},
number = {Suppl 2},
pages = {53-54},
pmid = {38123670},
issn = {1476-5454},
mesh = {Humans ; *Intravitreal Injections ; *Angiogenesis Inhibitors/administration &amp; dosage/adverse effects/therapeutic use ; Macular Degeneration/drug therapy ; Wet Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity ; Treatment Outcome ; Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects/administration &amp; dosage ; },
}
@article {pmid38123443,
year = {2024},
author = {Pot, E and Guenezan, L and Pelen, F and Facon, G},
title = {[Evaluation of an experiment in ophthalmology telemedicine].},
journal = {Journal francais d'ophtalmologie},
volume = {47},
number = {3},
pages = {103986},
doi = {10.1016/j.jfo.2023.05.030},
pmid = {38123443},
issn = {1773-0597},
mesh = {Humans ; *Ophthalmology ; *Cataract ; *Diabetic Retinopathy/diagnosis/epidemiology/therapy ; Emergency Service, Hospital ; *Telemedicine ; },
abstract = {PURPOSE: To meet the need for access to eye care in an area with a lack of physicians, a telemedicine workstation in ophthalmology was created. The main objective was to measure the improved access to eye care via telemedicine consultation.<br><br>METHODS: No criteria of age, sex or geographical location were defined. Depending on the cause for the consultation and the results of the examinations conducted by an ophthalmic technician physically present in the center, the patient might be given a telemedicine consultation with an ophthalmologist. Eleven indicators were defined to achieve the study objectives. Data were compared with a reference eye care center.<br><br>RESULTS: The quality, safety of care, and medical benefits of telemedicine consultation were not inferior to those of the reference center. The consultations screened 25 cases of age-related macular degeneration, 240 glaucoma, 229 cataracts and 27 diabetic retinopathy. 88.5% of patients were included in a cooperative ophthalmologist/technician protocol, compared with 27.3% in the reference center (P<0.0001).<br><br>DISCUSSION: The telemedicine workstation must be linked to a main center located at most a one-hour drive away. The equipment must be adapted to the use of telemedicine and to allow the technician to perform the necessary assessments and examinations. The number of emergency department visits after telemedicine consultation at the telemedicine workstation was higher than the reference center, which may lead to a subsequent study.<br><br>CONCLUSION: Telemedicine consultation improves access to eye care in a medically under-served area.},
}
@article {pmid38117666,
year = {2024},
author = {Pietzuch, M and Mantel, I and Ambresin, A and Tappeiner, C and Nagyova, D and Donati, G and Pfister, IB and Schild, C and Garweg, JG},
title = {Intravitreal Dexamethasone as a Rescue for Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration with Persistent Disease Activity and High Treatment Demand.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {40},
number = {6},
pages = {361-369},
doi = {10.1089/jop.2023.0105},
pmid = {38117666},
issn = {1557-7732},
mesh = {Humans ; *Dexamethasone/administration &amp; dosage/therapeutic use ; Retrospective Studies ; Male ; *Intravitreal Injections ; Female ; Aged, 80 and over ; Aged ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Visual Acuity/drug effects ; Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Drug Implants ; Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Glucocorticoids/administration &amp; dosage/therapeutic use ; Wet Macular Degeneration/drug therapy ; Longitudinal Studies ; },
abstract = {Purpose: To assess the impact of switching to, or adding, an intravitreal dexamethasone implant (Dex; Ozurdex[®]) in anti-vascular endothelial growth factor (VEGF) therapy on disease stability and treatment intervals in eyes with neovascular age-related macular degeneration (nAMD) and persistent disease activity and high treatment demand. Methods: This retrospective noncomparative multicenter longitudinal case series included pseudophakic eyes with nAMD and persistent retinal fluid despite regular anti-VEGF therapy (ranibizumab or aflibercept) that received at least 1 intravitreal Dex implant. Visual acuity, central retinal thickness (CRT), and intraocular pressure were recorded before, and after, the addition of Dex to anti-VEGF therapy. Results: Sixteen eyes of 16 patients met the inclusion criteria of persistent fluid despite anti-VEGF therapy, under treatment intervals of ≤7 weeks in 14 instances. Patients were 80.9 ± 7.4 years old and had received 25.5 ± 17.4 anti-VEGF injections before Dex over a period of 36.4 ± 21.9 months before switching. The treatment interval increased from 5.5 ± 3.2 weeks between the last anti-VEGF and first Dex injection to 11.7 ± 7.3 weeks thereafter (P = 0.022). CRT remained stable (385.3 ± 152.1, 383.9 ± 129.7, and 458.3 ± 155.2 μm before switching as well as 12 and 24 months after switching; P = 0.78 and P = 0.36, respectively). An insignificant mean short-term early increase in visual acuity was not sustained over time. Conclusions: The addition of Dex resulted in a relevant and sustained increase in treatment intervals, whereas CRT and visual acuity remained stable in these difficult-to-treat eyes. It may be discussed whether inflammation or other steroid-responsive factors play a significant role in cases of nAMD with nonsatisfactory responses to anti-VEGF.},
}
@article {pmid38117599,
year = {2023},
author = {Bikbov, MM and Kazakbaeva, GM and Gilmanshin, TR and Iakupova, EM and Fakhretdinova, AA and Tuliakova, AM and Panda-Jonas, S and Rusakova, IA and Gilemzianova, LI and Khakimov, DA and Miniazeva, LA and Usubov, EL and Jonas, JB},
title = {Prevalence and Associations of Keratoconus Among Children, Adults, and Elderly in the Population-Based Ural Eye Studies.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {6},
pages = {591-603},
doi = {10.1097/APO.0000000000000639},
pmid = {38117599},
issn = {2162-0989},
mesh = {Adult ; Humans ; Child ; Aged ; Adolescent ; Prevalence ; *Keratoconus/diagnosis/epidemiology ; Hand Strength ; Eye ; *Macular Degeneration/epidemiology ; },
abstract = {PURPOSE: To estimate prevalence and associations of keratoconus in populations in Russia with an age from childhood to seniority.<br><br>METHODS: The study population consisted of the cohorts of 3 population-based studies performed in urban and rural areas within the same geographical region in Bashkortostan/Russia: the Ural Children Eye Study (UCES; age = 6-18 y; n = 4890), the Ural Eye and Medical Study (UEMS; age = >40 y; n = 5314), and the Ural Very Old Study (UVOS; age = >85 y; n = 651). Based on Scheimflug imaging, keratoconus was defined by a keratometric reading of &#x2265;48 diopters (D) in any eye.<br><br>RESULTS: The mean maximal and minimal corneal refractive power increased from the UCES (43.58 &#xb1; 1.50&#x2002;D and 42.70 &#xb1; 1.42&#x2002;D, respectively) to the UEMS (44.26 &#xb1; 1.70&#x2002;D and 43.61 &#xb1; 1.76&#x2002;D, respectively) and to the UVOS (45.1 &#xb1; 1.72&#x2002;D and 43.98 &#xb1; 1.68&#x2002;D, respectively). Correspondingly, keratoconus prevalence increased from the UCES (42/4890; 0.086%; 95% CI = 0.060, 0.112) to the UEMS (112/5314; 2.11%; 95% CI = 1.72, 2.49) and to the UVOS (42/651; 6.45%; 95% CI = 4.56, 8.34). In the UCES, higher keratoconus prevalence was associated (multivariable analysis) with higher birth order [odds ratio (OR) = 2.34; 95% CI = 1.32, 4.15; P = 0.004], lower birth weight (OR = 0.99; 95% CI = 0.99, 0.99; P < 0.001), and shorter axial length (OR = 0.15; 95% CI = 0.08, 0.30; P < 0.001). In the UEMS, keratoconus prevalence correlated with shorter axial length (OR = 0.15; 95% CI = 0.10, 0.23; P < 0.001), larger corneal volume (OR = 1.17; 95% CI = 1.09, 1.25; P = 0.001), thicker lens (OR = 2.27; 95% CI = 1.06, 5.28; P = 0.04), cortical cataract degree (OR = 1.02; 95% CI = 1.01, 1.04; P = 0.01), and higher stage of age-related macular degeneration (OR = 1.65; 95% CI = 1.09, 2.51; P = 0.02). In the UVOS, keratoconus prevalence correlated with lower educational level (OR = 0.84; 95% CI = 0.71, 0.99; P = 0.04) and lower dynamometric handgrip force (OR = 0.92; 95% CI = 0.88, 0.97; P = 0.003).<br><br>CONCLUSIONS: In this study on multiethnic groups from Russia, keratoconus prevalence increased from the pediatric group (0.09%) to the adult group (2.11%) and seniority group (6.45%), correlated mostly with biometric ocular parameters and was in all age groups statistically independent of most systemic parameters.},
}
@article {pmid38117581,
year = {2024},
author = {Amari, B and Merle, BMJ and Korobelnik, JF and Delyfer, MN and Boniol, M and Dore, JF and Helmer, C and Delcourt, C and Cougnard-Gregoire, A},
title = {LIFETIME AMBIENT ULTRAVIOLET RADIATION EXPOSURE AND INCIDENCE OF AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {1},
pages = {28-36},
doi = {10.1097/IAE.0000000000003917},
pmid = {38117581},
issn = {1539-2864},
support = {001/WHO_/World Health Organization/International ; },
mesh = {Humans ; Child, Preschool ; Incidence ; *Ultraviolet Rays/adverse effects ; Prospective Studies ; Risk Factors ; *Macular Degeneration/diagnosis/epidemiology/etiology ; },
abstract = {PURPOSE: To investigate the link between lifelong exposure to ultraviolet radiation (UVR) and the development of age-related macular degeneration (AMD).<br><br>METHODS: The Alienor study is a prospective population-based cohort involving 963 residents of Bordeaux, France, older than 73 years. A subset of 614 participants for advanced AMD and 422 participants for early AMD were included in the analysis. The participants' residential history combined with UVR estimates from the EuroSun satellite were used to estimate the amount of ambient UVR they have been exposed to over their lifetime. Age-related macular degeneration was classified from retinal fundus photographs and spectral domain optical coherence tomography at 2 to 3 years intervals over the 2006 to 2017 period. Associations between cumulative exposure to ultraviolet A, ultraviolet B, and total (total UV) and the incidence of early and advanced AMD were estimated using multivariate Cox models.<br><br>RESULTS: Intermediate quartiles of total UV, ultraviolet A, and ultraviolet B exposures were associated with a higher risk for incident early AMD (Hazard Ratio [HR] =2.01 [95% confidence interval [CI] = 1.27-3.13], HR = 2.20 [95% CI = 1.38-3.50], HR = 1.79 [95% CI = 1.13-2.80], respectively) as compared with the lower quartile. However, this risk did not further increase in the highest quartiles of exposure. None of the three types of UVR exposure was significantly associated with incident advanced AMD.<br><br>CONCLUSION: Despite an increased risk with intermediate compared with low UVR exposure, our study cannot confirm a dose-response relationship of UVR exposure with early AMD onset.},
}
@article {pmid38983062,
year = {2023},
author = {Edwards, G and Grillo, SL},
title = {Editorial: Women in retina: 2022.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1169163},
doi = {10.3389/fopht.2023.1169163},
pmid = {38983062},
issn = {2674-0826},
}
@article {pmid38983569,
year = {2022},
author = {Higashijima, F and Hasegawa, M and Yoshimoto, T and Kobayashi, Y and Wakuta, M and Kimura, K},
title = {Molecular mechanisms of TGFβ-mediated EMT of retinal pigment epithelium in subretinal fibrosis of age-related macular degeneration.},
journal = {Frontiers in ophthalmology},
volume = {2},
number = {},
pages = {1060087},
pmid = {38983569},
issn = {2674-0826},
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly, affecting the macula of the retina and resulting in vision loss. There are two types of AMD, wet and dry, both of which cause visual impairment. Wet AMD is called neovascular AMD (nAMD) and is characterized by the formation of choroidal neovascular vessels (CNVs) in the macula. nAMD can be treated with intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors, which help improve vision. However, approximately half the patients do not achieve satisfactory results. Subretinal fibrosis often develops late in nAMD, leading to irreversible photoreceptor degeneration and contributing to visual loss. Currently, no treatment exists for subretinal fibrosis, and the molecular mechanisms of fibrous tissue formation following neovascular lesions remain unclear. In this review, we describe the clinical features and molecular mechanisms of macular fibrosis secondary to nAMD. Myofibroblasts play an essential role in the development of fibrosis. This review summarizes the latest findings on the clinical features and cellular and molecular mechanisms of the pathogenesis of subretinal fibrosis in nAMD and discusses the potential therapeutic strategies to control subretinal fibrosis in the future.},
}
@article {pmid38983095,
year = {2023},
author = {Ahsanuddin, S and Rios, HA and Otero-Marquez, O and Macanian, J and Zhou, D and Rich, C and Rosen, RB},
title = {Flavoprotein fluorescence elevation is a marker of mitochondrial oxidative stress in patients with retinal disease.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1110501},
pmid = {38983095},
issn = {2674-0826},
abstract = {PURPOSE: Recent studies of glaucoma, age-related macular degeneration, and diabetic retinopathy have demonstrated that flavoprotein fluorescence (FPF) can be utilized non-invasively as an indicator of mitochondrial oxidative stress in the retina. However, a comprehensive assessment of the validity and reliability of FPF in differentiating between healthy and diseased eyes across multiple disease states is lacking. Here, we evaluate the sensitivity and specificity of FPF in discriminating between healthy and diseased eyes in four leading causes of visual impairment worldwide, one of which has not been previously evaluated using FPF. We also evaluate the association between FPF and visual acuity.<br><br>METHODS: A total of 88 eyes [21 eyes of 21 unaffected controls, 20 eyes from 20 retinal vein occlusion (RVO) patients, 20 eyes from 20 diabetic retinopathy (DR) patients, 17 eyes from 17 chronic exudative age-related macular degeneration (exudative AMD) patients, and 10 eyes from 10 central serous retinopathy (CSR) patients] were included in the present cross-sectional observational study. Eyes were imaged non-invasively using a specially configured fundus camera OcuMet Beacon[&#xae;] (OcuSciences, Ann Arbor, MI). The macula was illuminated using a narrow bandwidth blue light (455 - 470 nm) and fluorescence was recorded using a narrow notch filter to match the peak emission of flavoproteins from 520 to 540 nm. AUROC analysis was used to determine the sensitivity of FPF in discriminating between diseased eyes and healthy eyes. Nonparametric Kruskal-Wallis Tests with post-hoc Mann Whitney U tests with the Holm-Bonferroni correction were performed to assess differences in FPF intensity, FPF heterogeneity, and best corrected visual acuity (BCVA) between the five groups. Spearman rank correlation coefficients were calculated to assess the relationship between FPF and BCVA.<br><br>RESULTS: AUROC analysis indicated that FPF intensity is highly sensitive for detecting disease, particularly for exudative AMD subjects (0.989; 95% CI = 0.963 - 1.000, p=3.0 x 10[7]). A significant difference was detected between the FPF intensity, FPF heterogeneity, and BCVA in all four disease states compared to unaffected controls (Kruskal-Wallis Tests, p = 1.06 x 10[-8], p = 0.002, p = 5.54 x 10[-8], respectively). Compared to healthy controls, FPF intensity values were significantly higher in RVO, DR, exudative AMD, and CSR (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). Spearman rank correlation coefficient between FPF intensity and BCVA was &#x3c1; = 0.595 (p = 9.62 x 10[-10]).<br><br>CONCLUSIONS: Despite variations in structural retinal findings, FPF was found to be highly sensitive for detecting retinal disease. Significant FPF elevation were seen in all four disease states, with the exudative AMD patients exhibiting the highest FPF values compared to DR, CSR, and RVO subjects. This is consistent with the hypothesis that there is elevated oxidative stress in all of these conditions as previously demonstrated by blood studies. FPF intensity is moderately correlated with the late-in disease-marker BCVA, which suggests that the degree of FPF elevation can be used as a metabolic indicator of disease severity.},
}
@article {pmid38983087,
year = {2023},
author = {Cruz-Aguilar, M and Groman-Lupa, S and Jiménez-Martínez, MC},
title = {MicroRNAs as potential biomarkers and therapeutic targets in age-related macular degeneration.},
journal = {Frontiers in ophthalmology},
volume = {3},
number = {},
pages = {1023782},
pmid = {38983087},
issn = {2674-0826},
abstract = {Age-related macular degeneration (AMD) involves degenerative and neovascular alteration in the macular region of the retina resulting in central vision loss. AMD can be classified into dry (dAMD) and wet AMD (wAMD). There is no established treatment for dAMD, and therapies available for wAMD have limited success. Diagnosis in early AMD stages is difficult due to the absence of clinical symptoms. Currently, imaging tests are used in the diagnosis of AMD, but cannot predict the clinical course. The clinical limitations to establishing a diagnosis of AMD have led to exploration for innovative and more sensitive tests to support the diagnosis and prognosis of the disease. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that negatively regulate genes by post-transcriptional gene silencing. Because these molecules are dysregulated in various processes implicated in the pathogenesis of AMD, they could contribute to the early detection of the disease and monitoring of its progression. Studies of miRNA profiling have indicated several miRNAs as potential diagnostic biomarkers of AMD, but no approved biomarker is available at present for early AMD detection. Thus, understanding the function of miRNAs in AMD and their use as potential biomarkers may lead to future advances in diagnosis and treatment. Here we present a brief review of some of the miRNAs involved in regulating pathological processes associated with AMD and discuss several candidate miRNAs proposed as biomarkers or therapeutic targets for AMD.},
}
@article {pmid38299085,
year = {2023},
author = {Mehmedovic, A and Sofic-Drino, V and Biscevic, A and Ahmedbegovic-Pjano, M},
title = {Intravitreal Sustained-release Dexamethasone Implant in Treatment for Chronic Macular Edema in Syphilis Infection: a Case Report.},
journal = {Medical archives (Sarajevo, Bosnia and Herzegovina)},
volume = {77},
number = {5},
pages = {405-408},
pmid = {38299085},
issn = {1986-5961},
mesh = {Male ; Humans ; Adult ; *Macular Edema/drug therapy/etiology/diagnosis ; Glucocorticoids/therapeutic use ; Dexamethasone/therapeutic use ; Delayed-Action Preparations/therapeutic use ; *Syphilis/complications/drug therapy ; Endothelial Cells ; Drug Implants/therapeutic use ; Edema/complications ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: Macular edema results from many conditions, such as diabetic retinopathy, macular degeneration, inflammatory diseases, cataract operation, trauma, and tumors. Specifically, the capillary filtration rate should equal the speed of fluid removal from extracellular retinal tissue, such as the glial and retinal pigment epithelium cells layer (RPE). Once these forces are imbalanced, fluid accumulates in cystoid spaces within the inner layers of the retina.<br><br>OBJECTIVE: The main purpose of this case report is to show that macular edema caused by any inflammation, either bacteria, virus, or autoimmune origin, can be treated successfully, even if it is chronic.<br><br>CASE REPORT: A 31-year-old man has been reported to our clinic with symptoms of blurry vision in the left eye, which occurred during the last year. Essential examinations included CDVA, IOP measurement, slit-lamp examination, indirect ophthalmoscopy, and OCT scan that showed significant macular edema (central foveal thickness of 353 microns). We initiated laboratory searches, such as blood, serology, and immunology testing for the next three months after his first visit, together with prescribed topical and periocular corticosteroid therapy. The test to VDRL (venereal disease research laboratory) for Syphilis and Toxocariasis came positive. We took the best decision and recommended further treatment with the intravitreal application of Dexamethasone Implant 0.7mg. One week after the intravitreal application of corticosteroids on the control exam, there were normal findings on the posterior segment with no macular edema (central foveal thickness of 269 microns).<br><br>CONCLUSION: It is unexclusive that infection by Treponema pallidum (TP) causes isolated macular edema without any other symptoms on the anterior segment of the eye. It has indirect action on the macula, not just causing papilledema, retinal vasculitis, retinochoroiditis, and inflammatory disc edema, as expected. TP or the bacteria transmembrane protein (treponemal ligands) directly acting on vascular endothelial cells of the RPE cells, will be the key to the most certain mechanism of this condition. It is related to the possibility of the secretion of cytokines and the interactions between immune cells indirectly.},
}
@article {pmid38455287,
year = {2022},
author = {Veldhuis, N and Nuijts, MA and Isphording, L and Lee-Kong, FVYL and Imhof, SM and Stegeman, I},
title = {Linguistic spin in randomized controlled trials about age-related macular degeneration.},
journal = {Frontiers in epidemiology},
volume = {2},
number = {},
pages = {961996},
pmid = {38455287},
issn = {2674-1199},
abstract = {OBJECTIVE: To evaluate the prevalence, type and extent of linguistic spin in randomized controlled trials (RCTs) exploring interventions in patients with age-related macular degeneration (AMD), as well as to investigate whether study variables were correlated with linguistic spin.<br><br>STUDY DESIGN AND SETTING: PubMed was searched from 2011 to 2020 to identify RCTs including patients with AMD. Two authors independently assessed a total of 96 RCTs. Linear regression analyses were performed to investigate whether linguistic spin was correlated with predefined study variables.<br><br>RESULTS: Linguistic spin was found in 61 of 96 abstracts (63.5%) and in 90 of 96 main texts (93.8%). Use of words pointing out the beneficial effect of a treatment and the use of '(statistically) significant/significance' without reporting a P-value or a 95% confidence interval (CI) were the most frequently identified categories of linguistic spin. Sample size was significantly correlated with the total linguistic spin score (95% CI 0.38-5.23, P = 0.02).<br><br>CONCLUSION: A high prevalence and extent of linguistic spin in RCTs about AMD was found. We highlighted the importance of objective reporting and awareness of linguistic spin among ophthalmologists and other readers.},
}
@article {pmid38983525,
year = {2022},
author = {Savastano, MC and Fossataro, C and Carlà, MM and Fantozzi, C and Falsini, B and Savastano, A and Rizzo, C and Kilian, R and Rizzo, S},
title = {OCT angiography analysis of choriocapillaris vascular density in different stages of age-related macular degeneration.},
journal = {Frontiers in ophthalmology},
volume = {2},
number = {},
pages = {985262},
pmid = {38983525},
issn = {2674-0826},
abstract = {OBJECTIVES: To analyze the choriocapillaris vessel density (CVD) of eyes at different stages of Age-related Macular Degeneration (AMD) with Optical Coherence Tomography Angiography (OCTA).<br><br>METHODS: This is a prospective observational cross-sectional study on 21 age-matched healthy eyes and 84 eyes with AMD (i.e., early AMD, late AMD, Geographic Atrophy [GA], and disciform scar AMD). OCTA was used to automatically measure the CVD (%), on both the whole macula and the foveal area, in a layer going from 9 &#xb5;m above to 30 &#xb5;m below the Bruch's membrane. Furthermore, in the GA subgroup, the extension of the Ellipsoid Zone (EZ) interruption and the area of macular chorio-retinal atrophy was analyzed.<br><br>RESULTS: Macular CVD was significantly lower in the GA, late AMD and disciform scar AMD-subgroups compared to controls (respectively, p=0.0052; p<0.0001; p=0.0003), whereas it did not significantly vary in the early AMD group (p=0.86). A significant difference between the early AMD and both the late AMD and the disciform scar AMD subgroups was also found (p=0.0009 and 0.0095, respectively). When comparing the foveal CVD of healthy and AMD eyes, a significant difference was found with every AMD subgroup (early AMD, p=0.011; GA, p<0.0001; late AMD, p<0.0001; disciform scar AMD, p<0.0001). Furthermore, in the GA subgroup, the CVD had an inverse correlation with both the extension of the EZ-interruption (p=0.012) and with the calculated chorio-retinal atrophic area (p=0.009).<br><br>CONCLUSIONS: OCTA could play a crucial role in the categorization of AMD, allowing for the evaluation of gradual flow impairment at different stages of the disease. Moreover, the detection of a decreased macular and foveal CVD may shed light on the pathogenesis of AMD.},
}
@article {pmid38390616,
year = {2022},
author = {Soliño, M and Larrayoz, IM and López, EM and Rey-Funes, M and Bareiro, M and Loidl, CF and Girardi, E and Caltana, L and Brusco, A and Martínez, A and López-Costa, JJ},
title = {CB1 Cannabinoid Receptor is a Target for Neuroprotection in Light Induced Retinal Degeneration.},
journal = {Advances in drug and alcohol research},
volume = {2},
number = {},
pages = {10734},
pmid = {38390616},
issn = {2674-0001},
abstract = {In the last few years, an increasing interest in the neuroprotective effect of cannabinoids has taken place. The aim of the present work was to study the effects of modulating cannabinoid receptor 1 (CB1) in the context of light induced retinal degeneration (LIRD), using an animal model that resembles many characteristics of human age-related macular degeneration (AMD) and other degenerative diseases of the outer retina. Sprague Dawley rats (n = 28) were intravitreally injected in the right eye with either a CB1 agonist (ACEA), or an antagonist (AM251). Contralateral eyes were injected with respective vehicles as controls. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h. Retinas from 28 animals were processed by GFAP-immunohistochemistry (IHC), TUNEL technique, Western blotting (WB), or qRT-PCR. ACEA-treated retinas showed a significantly lower number of apoptotic nuclei in the outer nuclear layer (ONL), lower levels of activated Caspase-3 by WB, and lower levels of glial reactivity by both GFAP-IHC and WB. qRT-PCR revealed that ACEA significantly decreased the expression of Bcl-2 and CYP1A1. Conversely, AM251-treated retinas showed a higher number of apoptotic nuclei in the ONL, higher levels of activated Caspase-3 by WB, and higher levels of glial reactivity as determined by GFAP-IHC and WB. AM251 increased the expression of Bcl-2, Bad, Bax, Aryl hydrocarbon Receptor (AhR), GFAP, and TNFα. In summary, the stimulation of the CB1 receptor, previous to the start of the pathogenic process, improved the survival of photoreceptors exposed to LIRD. The modulation of CB1 activity may be used as a neuroprotective strategy in retinal degeneration and deserves further studies.},
}
@article {pmid38983510,
year = {2022},
author = {Chantarasorn, Y and Smitthimathin, W and Vorasayan, P},
title = {The role of dual antiplatelets in geographic atrophy secondary to non-neovascular aged-related macular degeneration.},
journal = {Frontiers in ophthalmology},
volume = {2},
number = {},
pages = {984903},
pmid = {38983510},
issn = {2674-0826},
abstract = {BACKGROUND: To evaluate the effects of dual antiplatelets on progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and to determine additional factors predicting rapid GA growth.<br><br>MATERIAL AND METHODS: In this retrospective cohort study, patients with unifocal GA were consecutively enrolled (one eye per patient) from 2018 to 2021. The patients were categorized as 1. those receiving dual antiplatelet therapy containing a daily dose of 75 mg clopidogrel plus 81 mg aspirin (DAPT group), and 2. those not receiving DAPT (control group). Areas of GA, based on red-filtered fundus autofluorescence, were measured at baseline, and at 3, 6, and 12 months. The primary outcome was absolute 12-month changes in the square root (SQRT) area.<br><br>RESULTS: One eye in each group developed neovascular AMD and was excluded from the analysis. The DAPT (24 eyes) and control (22 eyes) groups had comparable age and baseline SQRT area (1.2 &#xb1; 0.27 and 1.8 &#xb1; 0.41&#xa0;mm, respectively; p adjusted for age = 0.23). At 12 months, after controlling for age and the presence of soft drusen or reticular pseudodrusen, patients receiving DAPT had fewer changes in the SQRT area than that of the control group (0.097 vs. 0.17&#xa0;mm; p = 0.02). The presence of drusen significantly predicted increased GA growth and choroidal thickness reduction.<br><br>CONCLUSIONS: Routine uses of dual antiplatelets were associated with decelerating GA growth. Drusen-associated GA may represent a generalized form of choroidal vascular alterations.},
}
@article {pmid38983565,
year = {2022},
author = {Titi-Lartey, O and Mohammed, I and Amoaku, WM},
title = {Toll-Like Receptor Signalling Pathways and the Pathogenesis of Retinal Diseases.},
journal = {Frontiers in ophthalmology},
volume = {2},
number = {},
pages = {850394},
pmid = {38983565},
issn = {2674-0826},
abstract = {There is growing evidence that the pathogenesis of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) have a significant chronic inflammatory component. A vital part of the inflammatory cascade is through the activation of pattern recognition receptors (PRR) such as toll-like receptors (TLR). Here, we reviewed the past and current literature to ascertain the cumulative knowledge regarding the effect of TLRs on the development and progression of retinal diseases. There is burgeoning research demonstrating the relationship between TLRs and risk of developing retinal diseases, utilising a range of relevant disease models and a few large clinical investigations. The literature confirms that TLRs are involved in the development and progression of retinal diseases such as DR, AMD, and ischaemic retinopathy. Genetic polymorphisms in TLRs appear to contribute to the risk of developing AMD and DR. However, there are some inconsistencies in the published reports which require further elucidation. The evidence regarding TLR associations in retinal dystrophies including retinitis pigmentosa is limited. Based on the current evidence relating to the role of TLRs, combining anti-VEGF therapies with TLR inhibition may provide a longer-lasting treatment in some retinal vascular diseases.},
}
@article {pmid38506178,
year = {2023},
author = {Mba Aki, T and Mouinga Abayi, AD and Manomba Boulingui, C and Assoumou, PA and Anyunzoghe, E and Vouma, M and Mistoul, I and Mve, M},
title = {[Causes of visual impairment among people living with HIV at the University Hospital of Libreville].},
journal = {Le Mali medical},
volume = {38},
number = {2},
pages = {17-22},
pmid = {38506178},
issn = {1993-0836},
abstract = {INTRODUCTION: Few data exist on the issue of visual impairment (VI) in people living with HIV (PLHIV).<br><br>OBJECTIVE: To identify the causes of visual impairment among people living with HIV (PLHIV) at the University Hospital of Libreville.<br><br>POPULATION AND METHODS: This was an observational study of 737 people living with HIV (PLHIV). The parameters studied were age (year), gender, CD4 count, age of infection, use of antiretroviral therapy as well as visual acuity from far and near (CMI-11) and cause of VI.<br><br>RESULTS: Out of a population of 737 PLHIV, 75 (101 eyes) had VI, representing a hospital prevalence of 10.2% (n = 75/737). VI was bilateral for 34.7% (n = 26/75) of them. The main aetiology were refractive disorders (47.5%). Uveitis affected 16.8% of the number of eyes, of which 12.9% were of toxoplasmic origin. Other causes were cataracts (11.9%) and cytomegalovirus retinitis (10.9%). Two patients experienced early macular degeneration and two others with macular ischemia. Bilateral macular hemorrhage and occlusion of the central artery of the retina were also observed.<br><br>CONCLUSION: One in 10 PLHIV is visually impaired. In half of the cases, the pathologies that provide this handicap, are opportunistic disease with ocular toxoplasmosis in the foreground. Routine screening may improve visual prognosis.},
}
@article {pmid38835692,
year = {2021},
author = {Plössl, K and Milenkovic, A and Weber, BHF},
title = {Challenges and opportunities for modeling monogenic and complex disorders of the human retina via induced pluripotent stem cell technology.},
journal = {Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V},
volume = {33},
number = {3},
pages = {221-227},
pmid = {38835692},
issn = {1863-5490},
abstract = {The human retina is a highly structured and complex neurosensory tissue central to perceiving and processing visual signals. In a healthy individual, the close interplay between the neuronal retina, the adjacent retinal pigment epithelium and the underlying blood supply, the choriocapillaris, is critical for maintaining eyesight over a lifetime. An impairment of this delicate and metabolically highly active system, caused by genetic alteration, environmental impact or both, results in a multitude of pathological phenotypes of the retina. Understanding and treating these disease processes are motivated by a marked medical need in young as well as in older patients. While naturally occurring or gene-manipulated animal models have been used successfully in ophthalmological research for many years, recent advances in induced pluripotent stem cell technology have opened up new avenues to generate patient-derived retinal model systems. Here, we explore to what extent these cellular models can be useful to mirror human pathologies in vitro ultimately allowing to analyze disease mechanisms and testing treatment options in the cell type of interest on an individual patient-specific genetic background.},
}
@article {pmid38755790,
year = {2020},
author = {Liew, G and Tse, B and Ho, IV and Joachim, N and White, A and Pickford, R and Maltby, D and Gopinath, B and Mitchell, P and Crossett, B},
title = {Acylcarnitine Abnormalities Implicate Mitochondrial Dysfunction in Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {61},
number = {8},
pages = {32},
pmid = {38755790},
issn = {1552-5783},
abstract = {PURPOSE: Abnormalities in lipid metabolism are implicated in age-related macular degeneration (AMD), but the pathways involved remain unclear. We assessed whether acylcarnitine concentrations, a marker of lipid and mitochondrial metabolism, differed between patients with AMD and controls.<br><br>METHODS: In this cross-sectional case-control study, cases (n = 81) had neovascular AMD and controls (n = 79) had cataract with no other ocular pathology. Participants were recruited from eye clinics in Western Sydney, Australia, between 2016 and 2018. Plasma blood samples were collected and liquid chromatography mass spectrometry analyses performed to identify acylcarnitine concentrations. Acylcarnitine levels were adjusted for age, gender and smoking in multivariable models. Confirmation of key acylcarnitine identities was conducted using high mass accuracy liquid chromatography-tandem mass spectrometry.<br><br>RESULTS: After multivariable adjustment, C2-carnitine (acetylcarnitine) levels were significantly lower in patients with neovascular AMD compared to controls (0.810 &#xb1; 0.053 (standard error) compared to 1.060 &#xb1; 0.053), p = 0.002). C18:2-DC carnitine (a dicarboxylic acylcarnitine with a 18 carbon side chain and 2 double bonds), levels were significantly higher in patients with neovascular AMD compared to controls (1.244 &#xb1; 0.046 compared to 1.013 &#xb1; 0.046), p = 0.001). Other acylcarnitines examined were not significantly different between cases and controls.<br><br>CONCLUSIONS: Reduced plasma levels of C2-carnitine (acetylcarnitine) and increased plasma levels of C18:2-DC carnitine were observed in patients with neovascular AMD compared to controls. These findings suggest mitochondrial dysfunction could be involved in the pathogenesis of neovascular AMD.},
}
@article {pmid38755787,
year = {2020},
author = {Xiong, YZ and Kwon, M and Bittner, AK and Virgili, G and Giacomelli, G and Legge, GE},
title = {Relationship Between Acuity and Contrast Sensitivity: Differences Due to Eye Disease.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {61},
number = {6},
pages = {40},
pmid = {38755787},
issn = {1552-5783},
support = {R01 EY027857/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Visual acuity (VA) and contrast sensitivity (CS) characterize different aspects of visual function. Whereas VA is a standard test in routine eye exams and clinical trials, CS is often not included. We investigated the pathology-specific dissociation between VA and CS by quantifying and comparing the relationship between these two measures in common ocular pathologies.<br><br>METHODS: VA and CS data were assembled from 1113 subjects, including groups with cataract (n = 450), age-related macular degeneration (AMD; n = 232), glaucoma (n = 100), retinitis pigmentosa (RP; n = 87), and normal ocular health (n = 244). VA and CS were measured by the Early Treatment Diabetic Retinopathy Study chart and Pelli-Robson chart, respectively.<br><br>RESULTS: Even when VA was relatively normal (<0.3 logMAR), the four ocular pathology groups showed quantitatively different mean CS deficits relative to normal controls, ranging from -0.01 log units for cataract to 0.23 log units for RP. When the entire range of VA was considered, the corresponding deficits in CS were noticeably different across these four groups, being least for cataract and progressively more severe for glaucoma, AMD, and RP. For every 1.0 logMAR loss of VA, the corresponding deficit in CS ranged from 0.22 logCS for cataract to 0.97 logCS for RP.<br><br>CONCLUSIONS: The quantitative relationship between VA and CS depends on the ocular pathology. CS appears to provide valuable complementary information to VA in the early detection of eye disease and when evaluating visual impairment.},
}
@article {pmid38115754,
year = {2024},
author = {Li, M and Wang, P and Huo, ST and Qiu, H and Li, C and Lin, S and Guo, L and Ji, Y and Zhu, Y and Liu, J and Guo, J and Na, J and Hu, Y},
title = {Human Pluripotent Stem Cells Derived Endothelial Cells Repair Choroidal Ischemia.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {11},
number = {9},
pages = {e2302940},
pmid = {38115754},
issn = {2198-3844},
support = {2022YFA1103103//National Key Research and Development Program of China/ ; 2022YFA0913300//National Key Research and Development Program of China/ ; 2019YFA0110001//National Key Research and Development Program of China/ ; 81970818//National Natural Science Foundation of China/ ; 31970819//National Natural Science Foundation of China/ ; 32270784//National Natural Science Foundation of China/ ; 82371075//National Natural Science Foundation of China/ ; 2021Z99CFY033//Tsinghua University Spring Breeze Fund/ ; 10001020106//Tsinghua University Initiative Scientific Research Program of Precision Medicine/ ; },
mesh = {Humans ; Animals ; Rats ; Endothelial Cells/physiology ; *Myopia, Degenerative ; *Pluripotent Stem Cells ; Ischemia/therapy ; Atrophy ; },
abstract = {Choroidal atrophy is a common fundus pathological change closely related to the development of age-related macular degeneration (AMD), retinitis pigmentosa, and pathological myopia. Studies suggest that choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first cells lost in choroidal atrophy. It is found that endothelial cells derived from human pluripotent stem cells (hPSC-ECs) through the MESP1+ mesodermal progenitor stage express CECs-specific markers and can integrate into choriocapillaris. Single-cell RNA-seq (scRNA-seq) studies show that hPSC-ECs upregulate angiogenesis and immune-modulatory and neural protective genes after interacting with ex vivo ischemic choroid. In a rat model of choroidal ischemia (CI), transplantation of hPSC-ECs into the suprachoroidal space increases choroid thickness and vasculature density. Close-up examination shows that engrafted hPSC-ECs integrate with all layers of rat choroidal vessels and last 90 days. Remarkably, EC transplantation improves the visual function of CI rats. The work demonstrates that hPSC-ECs can be used to repair choroidal ischemia in the animal model, which may lead to a new therapy to alleviate choroidal atrophy implicated in dry AMD, pathological myopia, and other ocular diseases.},
}
@article {pmid38115358,
year = {2023},
author = {Li, G and Zhu, N and Ji, A},
title = {Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials.},
journal = {Medicine},
volume = {102},
number = {50},
pages = {e36370},
pmid = {38115358},
issn = {1536-5964},
mesh = {*Antibodies, Bispecific/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/therapy ; Humans ; Randomized Controlled Trials as Topic ; *Macular Edema/etiology/therapy ; *Diabetes Complications/therapy ; Treatment Outcome ; },
abstract = {INTRODUCTION: A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME).<br><br>MATERIALS AND METHODS: A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies.<br><br>RESULTS: A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD&#x2005;=&#x2005;-2.42, 95% CI [-3.93 to -0.90], P&#x2005;=&#x2005;.002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD&#x2005;=&#x2005;-22.41, 95% CI [-29.95 to -14.86], P&#x2005;<&#x2005;.00001) and the number of injections(MD&#x2005;=&#x2005;-0.93, 95% CI [-1.33 to -0.54], P&#x2005;<&#x2005;.00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events.<br><br>CONCLUSIONS: Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.},
}
@article {pmid38114564,
year = {2023},
author = {An, S and Yu, H and Islam, MDM and Zhang, X and Zhan, Y and Olivieri, JJ and Ambati, J and Yao, J and Gelfand, BD},
title = {Effects of donor-specific microvascular anatomy on hemodynamic perfusion in human choriocapillaris.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {22666},
pmid = {38114564},
issn = {2045-2322},
support = {R01 EY032512/EY/NEI NIH HHS/United States ; R01 AG078892/AG/NIA NIH HHS/United States ; R01EY031039/NH/NIH HHS/United States ; R01 EY028027/EY/NEI NIH HHS/United States ; R01 AG082748/AG/NIA NIH HHS/United States ; R01 HL164592/HL/NHLBI NIH HHS/United States ; R01 EY029799/EY/NEI NIH HHS/United States ; R01 EY031039/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid/blood supply ; *Macular Degeneration/pathology ; Hemodynamics ; Perfusion ; },
abstract = {Evidence from histopathology and clinical imaging suggest that choroidal anatomy and hemodynamic perfusion are among the earliest changes in retinal diseases such as age-related macular degeneration (AMD). However, how inner choroidal anatomy affects hemodynamic perfusion is not well understood. Therefore, we sought to understand the influences of choroidal microvascular architecture on the spatial distribution of hemodynamic parameters in choriocapillaris from human donor eyes using image-based computational hemodynamic (ICH) simulations. We subjected image-based inner choroid reconstructions from eight human donor eyes to ICH simulation using a kinetic-based volumetric lattice Boltzmann method to compute hemodynamic distributions of velocity, pressure, and endothelial shear stress. Here, we demonstrate that anatomic parameters, including arteriolar and venular arrangements and intercapillary pillar density and distribution exert profound influences on inner choroidal hemodynamic characteristics. Reductions in capillary, arteriolar, and venular density not only reduce the overall blood velocity within choriocapillaris, but also substantially increase its spatial heterogeneity. These first-ever findings improve understanding of how choroidal anatomy affects hemodynamics and may contribute to pathogenesis of retinal diseases such as AMD.},
}
@article {pmid38114333,
year = {2023},
author = {Sadda, SR and Bradvica, M and Vajas, A and Sagong, M and Ernest, J and Studnička, J and Veith, M and Wylegala, E and Patel, S and Yun, C and Orski, M and Astakhov, S and Tóth-Molnár, E and Csutak, A and Enyedi, L and Choi, W and Oh, I and Jang, H and Woo, SJ},
title = {Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial.},
journal = {BMJ open ophthalmology},
volume = {8},
number = {1},
pages = {},
pmid = {38114333},
issn = {2397-3269},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Biosimilar Pharmaceuticals/therapeutic use ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Prospective Studies ; Visual Acuity ; },
abstract = {BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Prospective, double-masked, randomised, phase 3 trial.<br><br>METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity.<br><br>RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 &#xb5;m and -132.4 &#xb5;m for SB15/SB15 and -126.6 &#xb5;m and -136.3 &#xb5;m for AFL/AFL, respectively (CST: difference (95% CI)=7.4 &#xb5;m (-6.11 to 20.96); TRT: difference (95% CI)=3.9 &#xb5;m (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups.<br><br>CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.},
}
@article {pmid38113868,
year = {2024},
author = {Nawrocka, ZA and Nawrocki, J},
title = {Fundus Autofluorescence Patterns in Subretinal Hemorrhages Associated with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {1},
pages = {58-64},
doi = {10.1159/000535865},
pmid = {38113868},
issn = {1423-0267},
mesh = {Humans ; *Tissue Plasminogen Activator ; Fibrinolytic Agents ; Retina ; Retinal Hemorrhage/diagnosis/etiology ; *Macular Degeneration/diagnosis ; Retrospective Studies ; Intravitreal Injections ; Fluorescein Angiography ; Tomography, Optical Coherence ; },
abstract = {INTRODUCTION: Submacular hemorrhage (SMH) is a vision-threatening complication of neovascular age-related macular degeneration (AMD). The exact treatment scheme is not established yet. The aim of the current study was to describe surgical results and fundus autofluorescence (FAF) patterns after pars plana vitrectomy (ppV) + subretinal tissue plasminogen activator (tPA) + anti-vascular endothelial growth factor (VEGF) and intravitreal tPA + anti-VEGF + sulfur hexafluoride (SF6) tamponade and to compare them to intravitreal tPA + anti-VEGF + SF6 in the treatment of SMH in the course of AMD.<br><br>MATERIALS AND METHODS: We performed FAF imaging in patients with a previous SMH in the course of AMD with a duration of <60 days treated with vitrectomy with subretinal anti-VEGF and tPA and intravitreal anti-VEGF, tPA, and SF6 administration (group 1) or intravitreal tPA + anti-VEGF + SF6 (group 2). In all eyes, a throughout ophthalmic examination, fluorescein angiography, and spectral domain optical coherence tomography (SD-OCT) were done for diagnosis. SD-OCT was performed monthly during treatment.<br><br>RESULTS: Three FAF patterns were observed in both groups. Pattern one (normal autofluorescence) was observed in 5/18 in group one and 5/21 group two. Pattern two was observed in 6/18 in group one and 7/21 in group two. Pattern three was noted in 7/18 in group one and 5/21 in group two. Improvement in visual acuity was statistically significant for both groups: 0.01 Snellen (2.0 logMAR) to 0.11 Snellen (0.96 logMAR) in group one (p = 0.019) and 0.11 Snellen (0.96 logMAR) to 0.33 Snellen (0.48 logMAR) in group two (p = 0.0007). Central retinal thickness also decreased with statistical significance for both groups (p < 0.05).<br><br>CONCLUSION: FAF patterns did not depend on the treatment used, but solely on the duration of SMH before treatment. SMH if not treated prompt enough might cause long-standing photoreceptor and retinal pigment epithelium defect, which is represented by hypo- and hyperautofluorescence. Performing a subretinal injection of tPA and anti-VEGF does not cause any defects associated with the injection site. That might be associated with previous local internal limiting membrane peeling, which reduces the injection pressure. Not only prompt treatment of SMH but also further continuation of anti-VEGF treatment is mandatory to maintain vision.},
}
@article {pmid38113800,
year = {2024},
author = {Ebrahimi, M and Ebrahimi, M and Vergroesen, JE and Aschner, M and Sillanpää, M},
title = {Environmental exposures to cadmium and lead as potential causes of eye diseases.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {82},
number = {},
pages = {127358},
doi = {10.1016/j.jtemb.2023.127358},
pmid = {38113800},
issn = {1878-3252},
mesh = {Humans ; Cadmium/toxicity/analysis ; Lead/toxicity ; Environmental Exposure/adverse effects ; *Metals, Heavy ; *Eye Diseases/chemically induced ; },
abstract = {Humans are exposed to cadmium and lead in various regions of the world daily due to industrial development and climate change. Increasing numbers of preclinical and clinical studies indicate that heavy metals, such as cadmium and lead, play a role in the pathogenesis of eye diseases. Excessive exposure to heavy metals such as cadmium and lead can increase the risk of impaired vision. Therefore, it is essential to better characterize the role of these non-essential metals in disease etiology and progression. This article discusses the potential role of cadmium and lead in the development of age-related eye diseases, including age-related macular degeneration, cataracts, and glaucoma. Furthermore, we discuss how cadmium and lead affect ocular cells and provide an overview of putative pathological mechanisms associated with their propensity to damage the eye.},
}
@article {pmid38113366,
year = {2023},
author = {},
title = {Erratum for "Functional Imaging of Mitochondria in Age-Related Macular Degeneration Using Flavoprotein Fluorescence".},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {12},
pages = {732},
doi = {10.3928/23258160-20231106-01},
pmid = {38113366},
issn = {2325-8179},
}
@article {pmid38113024,
year = {2024},
author = {Kim, YH and Yun, C and Oh, J},
title = {Integrity of the Hyperreflective Layer in the Inner Choroid in Eyes with Drusen.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {2},
pages = {529-540},
pmid = {38113024},
issn = {2193-8245},
support = {KMDF_PR_20200901_0026//Korea Medical Device Development Fund/ ; RS-2020-KD000026//Korea Medical Device Development Fund/ ; },
abstract = {INTRODUCTION: This study aimed to compare the integrity of the hyperreflective layer of the inner choroid in eyes with and without drusen.<br><br>METHODS: Swept-source optical coherence tomography images of patients with drusen and normal controls were reviewed. Using a line plot of ImageJ, choroidal reflectivity was measured at the subfovea, and the integrity of the hyperreflective layer of the inner choroid was determined.<br><br>RESULTS: In total, 63 eyes with drusen and 30 control eyes without drusen were included. The integrity of the hyperreflective layer of the inner choroid was preserved in 81.0% of eyes with drusen and 93.3% of normal controls. The proportion of eyes with the hyperreflective layer did not differ between eyes with and without drusen. Of the 63 subjects with drusen, this hyperreflective layer was observed in all 28 eyes (100%) with pachydrusen but only in 68.6% of the 35 eyes with soft drusen, and its prevalence was significantly different (P&#x2009;=&#x2009;0.001).<br><br>CONCLUSION: The prevalence of the hyperreflective layer between the choriocapillaris and medium or large choroidal vessels in eyes with soft drusen differed from that in eyes with pachydrusen. These findings support the suggestion that changes within the choroidal stroma may be involved in the pathogenesis of age-related macular degeneration.},
}
@article {pmid38111476,
year = {2023},
author = {Lapointe, N and Akitegetse, C and Poirier, J and Picard, M and Sauvageau, P and Sauvageau, D},
title = {Targeted spectroscopy in the eye fundus.},
journal = {Journal of biomedical optics},
volume = {28},
number = {12},
pages = {126004},
pmid = {38111476},
issn = {1560-2281},
mesh = {Humans ; Fundus Oculi ; *Retina ; *Optic Disk ; Oximetry/methods ; Spectrometry, Fluorescence ; },
abstract = {SIGNIFICANCE: The assessment of biomarkers in the eye is rapidly gaining traction for the screening, diagnosis, and monitoring of ocular and neurological diseases. Targeted ocular spectroscopy is a technology that enables concurrent imaging of the eye fundus and analysis of high-quality spectra from a targeted region within the imaged area. This provides structural, compositional, and functional information of specific regions of the eye fundus from a non-invasive approach to ocular biomarker detection.<br><br>AIM: The aim of our study was to demonstrate the multimodal functionality and validation of targeted ocular spectroscopy. This was done in vitro, using a reference target and a model eye, and in vivo.<br><br>APPROACH: Images and spectra from different regions of a reference target and a model eye were acquired and analyzed to validate the system. Targeted ocular fluorescence spectroscopy was also demonstrated with the same model. Subsequently, in vivo imaging and diffuse reflectance spectra were acquired to assess blood oxygen saturation in the optic nerve head and the parafovea of healthy subjects.<br><br>RESULTS: Tests conducted with the reference target showed accurate spectral analysis within specific areas of the imaging space. In the model eye, distinct spectral signatures were observed for the optic disc, blood vessels, the retina, and the macula, consistent with the variations in tissue composition and functions between these regions. An ocular oximetry algorithm was applied to in vivo spectra from the optic nerve head and parafovea of healthy patients, showing significant differences in blood oxygen saturation. Finally, targeted fluorescence spectral analysis was performed in vitro.<br><br>CONCLUSIONS: Diffuse reflectance and fluorescence spectroscopy in specific regions of the eye fundus open the door to a whole new range of monitoring and diagnostic capabilities, from assessment of oxygenation in glaucoma and diabetic retinopathy to photo-oxidation and photodegradation in age-related macular degeneration.},
}
@article {pmid38111140,
year = {2024},
author = {Inokaityte, I and Gedvilaite, G and Liutkeviciene, R},
title = {Association of TAS2R16 gene (rs860170, rs978739, rs1357949) polymorphisms and TAS2R16 serum levels in patients with age-related macular degeneration.},
journal = {Ophthalmic genetics},
volume = {45},
number = {1},
pages = {28-37},
doi = {10.1080/13816810.2023.2291681},
pmid = {38111140},
issn = {1744-5094},
mesh = {Female ; Humans ; Male ; Case-Control Studies ; Genotype ; Haplotypes ; *Macular Degeneration/diagnosis/genetics ; *Polymorphism, Single Nucleotide ; Taste Receptors, Type 2 ; },
abstract = {BACKGROUND: The aim of this study is to determine the association of TAS2R16 (rs860170, rs978739, rs1357949) gene polymorphisms and TAS2R16 serum levels in patients with the occurrence of age-related macular degeneration (AMD).<br><br>METHODS: Subjects with early AMD, subjects with exudative AMD, and healthy controls participated in the study. DNA was isolated by salting out leukocytes from peripheral venous blood. Single nucleotide polymorphisms (SNPs) were analysed by RT-PCR. TAS2R16 levels were determined by enzyme-linked immunosorbent assay (ELISA) using the Abbexa Human Taste Receptor Type 2 Member 16 (TAS2R16) ELISA kit. Statistical data analysis was performed using "IBM SPSS Statistics 27.0" and SNPstats statistical data analysis programmes.<br><br>RESULTS: The TAS2R16 rs860170 TT genotype is statistically significantly less frequent in the exudative AMD group than in the control group, whereas the TAS2R16 rs860170 C allele gene is statistically significantly more frequent in the exudative AMD group. Each C allele of TAS2R16 rs860170 is associated with a 2.8-fold increased probability of occurrence of exudative AMD. The C allele of TAS2R16 rs860170 is statistically significantly more frequent in men and women with exudative AMD than in the control group. The C allele of TAS2R16 rs860170 is associated with a 2.8-fold increased odds of occurrence of exudative AMD in women and a 2.9-fold increased odds of occurrence of exudative AMD in men. In TAS2R16 (rs860170, rs978739, and rs1357949), the T-T-A haplotype is associated with a 2.6-fold decreased likelihood of developing early AMD and the T-T-A haplotype is associated with a 3.2-fold decreased likelihood of developing early AMD in women. For TAS2R16 (rs860170, rs978739, and rs1357949), carriers of the T-T-G and T-T-A haplotypes are associated with a 2.2- and 3.2-fold decreased probability of exudative AMD, respectively. Individuals with the C-C-A haplotype are 9.2-fold more likely to develop exudative AMD. Specifically, the C-C-A haplotype is associated with a 9.3-fold increased likelihood of exudative AMD in men. In contrast, women with the T-T-A haplotype are 5.6-fold less likely to develop exudative AMD.<br><br>CONCLUSION: TAS2R16 plays an important role in the development of AMD.},
}
@article {pmid38110941,
year = {2023},
author = {Gu, Y and Sheng, F and Gao, M and Zhang, L and Hao, S and Chen, S and Chen, R and Xu, Y and Wu, D and Han, Y and Chen, L and Liu, Y and Lu, B and Zhao, W and Lou, X and Chen, Z and Li, P and Wang, X and Yao, K and Fu, Q},
title = {Acute and continuous exposure of airborne fine particulate matter (PM2.5): diverse outer blood-retinal barrier damages and disease susceptibilities.},
journal = {Particle and fibre toxicology},
volume = {20},
number = {1},
pages = {50},
pmid = {38110941},
issn = {1743-8977},
support = {82271063, 81670833, 81870641, 8207939, 81300641//National Natural Science Foundation of China/ ; 82271063, 81670833, 81870641, 8207939, 81300641//National Natural Science Foundation of China/ ; 2019C03091, 2020C03035//Key Research and Development Program of Zhejiang Province/ ; 2019C03091, 2020C03035//Key Research and Development Program of Zhejiang Province/ ; 2019QNA7026//Fundamental Research Funds for the Central Universities/ ; },
mesh = {Animals ; Mice ; Fluorescein Angiography/methods ; *Blood-Retinal Barrier ; Disease Susceptibility/pathology ; *Endothelial Cells ; Retinal Pigment Epithelium/pathology ; },
abstract = {BACKGROUND: The association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood-retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases.<br><br>OBJECTIVES: To describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities.<br><br>METHODS: A PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage.<br><br>RESULTS: Acute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation.<br><br>CONCLUSION: This study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation.},
}
@article {pmid38110385,
year = {2023},
author = {Armbrust, KR and Westanmo, A and Gravely, A and Chew, EY and van Kuijk, FJ},
title = {Adverse COVID-19 outcomes in American Veterans with age-related macular degeneration: a case-control study.},
journal = {BMJ open},
volume = {13},
number = {12},
pages = {e071921},
pmid = {38110385},
issn = {2044-6055},
mesh = {Humans ; United States/epidemiology ; Case-Control Studies ; *COVID-19/epidemiology/complications ; COVID-19 Testing ; *Veterans ; *Macular Degeneration/epidemiology/complications ; },
abstract = {OBJECTIVES: Prior studies suggest that patients with age-related macular degeneration (AMD) have poorer COVID-19 outcomes. This study aims to evaluate whether AMD is associated with adverse COVID-19 outcomes in a large clinical database.<br><br>DESIGN: Case-control study.<br><br>SETTING: We obtained demographic and clinical data from a national US Veterans Affairs (VA) database for all Veterans aged 50 years or older with positive COVID-19 testing prior to 2 May 2021.<br><br>The primary outcome measure was hospitalisation. Secondary outcome measures were intensive care unit admission, mechanical ventilation and death. Potential associations between AMD and outcome measures occurring within 60 days of COVID-19 diagnosis were evaluated using multiple logistic regression analyses.<br><br>RESULTS: Of the 171&#x2009;325 patients in the study cohort, 7913 (5%) had AMD and 2152 (1%) had severe AMD, defined as advanced atrophic or exudative AMD disease coding. Multiple logistic regression adjusting for age, Charlson Comorbidity Index, sex, race, ethnicity and COVID-19 timing showed that an AMD diagnosis did not significantly increase the odds of hospitalisation (p=0.11). Using a Bonferroni-adjusted significance level of 0.006, AMD and severe AMD also were not significant predictors for the secondary outcomes, except for AMD being modestly protective for death (p=0.002).<br><br>CONCLUSIONS: After adjusting for other variables, neither AMD nor severe AMD was a risk factor for adverse COVID-19 outcomes in the VA healthcare system. These findings indicate that an AMD diagnosis alone should not alter recommended ophthalmic management based on COVID-19 adverse outcome risk.},
}
@article {pmid38109866,
year = {2024},
author = {Landau Prat, D and Kapelushnik, N and Arazi, M and Zloto, O and Leshno, A and Klang, E and Sina, S and Segev, S and Soudry, S and Ben Simon, GJ},
title = {Glaucoma Prediction Models Based on Ocular and Systemic Findings.},
journal = {Ophthalmic research},
volume = {67},
number = {1},
pages = {29-38},
doi = {10.1159/000535879},
pmid = {38109866},
issn = {1423-0259},
mesh = {Male ; Humans ; Adult ; Middle Aged ; Aged ; *Glaucoma/diagnosis ; Eye ; Intraocular Pressure ; Tonometry, Ocular ; *Cataract/complications ; },
abstract = {INTRODUCTION: Our aim was to explore the impact of various systemic and ocular findings on predicting the development of glaucoma.<br><br>METHODS: Medical records of 37,692 consecutive patients examined at a single medical center between 2001 and 2020 were analyzed using machine learning algorithms. Systemic and ocular features were included. Univariate and multivariate analyses followed by CatBoost and Light gradient-boosting machine prediction models were performed. Main outcome measures were systemic and ocular features associated with progression to glaucoma.<br><br>RESULTS: A total of 7,880 patients (mean age 54.7 &#xb1; 12.6 years, 5,520 males [70.1%]) were included in a 3-year prediction model, and 314 patients (3.98%) had a final diagnosis of glaucoma. The combined model included 185 systemic and 42 ocular findings, and reached an ROC AUC of 0.84. The associated features were intraocular pressure (48.6%), cup-to-disk ratio (22.7%), age (8.6%), mean corpuscular volume (MCV) of red blood cell trend (5.2%), urinary system disease (3.3%), MCV (2.6%), creatinine level trend (2.1%), monocyte count trend (1.7%), ergometry metabolic equivalent task score (1.7%), dyslipidemia duration (1.6%), prostate-specific antigen level (1.2%), and musculoskeletal disease duration (0.5%). The ocular prediction model reached an ROC AUC of 0.86. Additional features included were age-related macular degeneration (10.0%), anterior capsular cataract (3.3%), visual acuity (2.0%), and peripapillary atrophy (1.3%).<br><br>CONCLUSIONS: Ocular and combined systemic-ocular models can strongly predict the development of glaucoma in the forthcoming 3 years. Novel progression indicators may include anterior subcapsular cataracts, urinary disorders, and complete blood test results (mainly increased MCV and monocyte count).},
}
@article {pmid38109663,
year = {2024},
author = {Ramtohul, P and Au, A and Kunkler, AL and Bacci, T and Dolz-Marco, R and Gallego-Pinazo, R and Yannuzzi, N and Sarraf, D and Freund, KB},
title = {CENTRAL BOUQUET HEMORRHAGE: Clinical and Multimodal Imaging Features.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {4},
pages = {551-557},
pmid = {38109663},
issn = {1539-2864},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Angiogenesis Inhibitors ; Cross-Sectional Studies ; Fluorescein Angiography/methods ; *Hemorrhage/diagnostic imaging/drug therapy ; Intravitreal Injections ; Multimodal Imaging ; Retrospective Studies ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage."<br><br>METHODS: Retrospective, observational, multicenter case series of eyes with central bouquet hemorrhage. Multimodal imaging features were reviewed and analyzed.<br><br>RESULTS: Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6 &#xb1; 21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia Type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with central bouquet hemorrhage displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer. Cross-sectional optical coherence tomography showed a well-delineated round hyperreflective lesion involving the central foveal Henle fiber layer/outer nuclear layer in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented Henle fiber layer were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36).<br><br>CONCLUSION: "Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with Henle fiber layer hemorrhage and encountered in a spectrum of macular disease.},
}
@article {pmid38108727,
year = {2023},
author = {Pierre, M and Lamaa, D and Fabre, M and Ronco, C and Benhida, R and Demange, L and Charrueau, C},
title = {[Topical treatment for age-related macular degeneration: Where are we now?].},
journal = {Medecine sciences : M/S},
volume = {39},
number = {12},
pages = {958-966},
doi = {10.1051/medsci/2023177},
pmid = {38108727},
issn = {1958-5381},
mesh = {Humans ; *Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Administration, Topical ; },
abstract = {The therapeutic management of age-related macular degeneration (AMD) is a major public health issue. One of its two late forms, neovascular AMD, is currently treated by intravitreal injections of pharmaceutical active ingredients. Although it is very effective in treating pathologies of the posterior segment of the eye, the intravitreal route is not an ideal option for the long-term management of a chronic disease such as AMD. Indeed, in the literature, some authors even call it a "burden" for the practitioners, the patients and the healthcare system. Thus, consideration should be given to less invasive routes. Among the possible administration routes to reach the posterior segment of the eye, the most suitable for the patient with the least risk of systemic adverse effects is the topical route. Several research teams have attempted to formulate molecules for topical administration in the treatment of atrophic or neovascular AMD. In this review, we emphasize the importance of the pharmaceutical formulation to meet the challenge of targeting the posterior segment of the eye by a topical route.},
}
@article {pmid38108689,
year = {2023},
author = {Zhang, JY and Xiao, J and Xie, B and Barba, H and Boachie-Mensah, M and Shah, RN and Nadeem, U and Spedale, M and Dylla, N and Lin, H and Sidebottom, AM and D'Souza, M and Theriault, B and Sulakhe, D and Chang, EB and Skondra, D},
title = {Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {15},
pages = {21},
pmid = {38108689},
issn = {1552-5783},
support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; },
mesh = {Male ; Female ; Animals ; Mice ; Angiogenesis Inhibitors ; RNA, Ribosomal, 16S ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Retina ; *Choroidal Neovascularization/prevention &amp; control ; },
abstract = {PURPOSE: Emerging data indicate that metformin may prevent the development of age-related macular degeneration (AMD). Whereas the underlying mechanisms of metformin's anti-aging properties remain undetermined, one proposed avenue is the gut microbiome. Using the laser-induced choroidal neovascularization (CNV) model, we investigate the effects of oral metformin on CNV, retinal pigment epithelium (RPE)/choroid transcriptome, and gut microbiota.<br><br>METHODS: Specific pathogen free (SPF) male mice were treated via daily oral gavage of metformin 300&#xa0;mg/kg or vehicle. Male mice were selected to minimize sex-specific differences to laser induction and response to metformin. Laser-induced CNV size and macrophage/microglial infiltration were assessed by isolectin and Iba1 immunostaining. High-throughput RNA-seq of the RPE/choroid was performed using Illumina. Fecal pellets were analyzed for gut microbiota composition/pathways with 16S rRNA sequencing/shotgun metagenomics, as well as microbial-derived metabolites, including small-chain fatty acids and bile acids. Investigation was repeated in metformin-treated germ-free (GF) mice and antibiotic-treated/GF mice receiving fecal microbiota transplantation (FMT) from metformin-treated SPF mice.<br><br>RESULTS: Metformin treatment reduced CNV size (P < 0.01) and decreased Iba1+ macrophage/microglial infiltration (P < 0.005). One hundred forty-five differentially expressed genes were identified in the metformin-treated group (P < 0.05) with a downregulation in pro-angiogenic genes Tie1, Pgf, and Gata2. Furthermore, metformin altered the gut microbiome in favor of Bifidobacterium and Akkermansia, with a significant increase in fecal levels of butyrate, succinate, and cholic acid. Metformin did not suppress CNV in GF mice but colonization of microbiome-depleted mice with metformin-derived FMT suppressed CNV.<br><br>CONCLUSIONS: These data suggest that oral metformin suppresses CNV, the hallmark lesion of advanced neovascular AMD, via gut microbiome modulation.},
}
@article {pmid38108061,
year = {2023},
author = {Hernandez, BJ and Skiba, NP and Plössl, K and Strain, M and Liu, Y and Grigsby, D and Kelly, U and Cady, MA and Manocha, V and Maminishkis, A and Watkins, T and Miller, SS and Ashley-Koch, A and Stamer, WD and Weber, BHF and Bowes Rickman, C and Klingeborn, M},
title = {Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.},
journal = {Journal of extracellular biology},
volume = {2},
number = {10},
pages = {},
pmid = {38108061},
issn = {2768-2811},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY028608/EY/NEI NIH HHS/United States ; R01 EY022359/EY/NEI NIH HHS/United States ; R21 EY033057/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; R01 EY032960/EY/NEI NIH HHS/United States ; F31 EY033170/EY/NEI NIH HHS/United States ; P30 EY031631/EY/NEI NIH HHS/United States ; },
abstract = {The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD).},
}
@article {pmid38106142,
year = {2023},
author = {Zhang, L and Cavallini, M and Wang, J and Xin, R and Zhang, Q and Feng, G and Sanes, JR and Peng, YR},
title = {Evolutionary and Developmental Specialization of Foveal Cell Types in the Marmoset.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.12.10.570996},
pmid = {38106142},
issn = {2692-8205},
abstract = {UNLABELLED: In primates, high-acuity vision is mediated by the fovea, a small specialized central region of the retina. The fovea, unique to the anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, the extent of cellular similarity across anthropoid foveas and the molecular underpinnings of foveal maturation remain unclear. Here, we used high throughput single cell RNA sequencing to profile retinal cells of the common marmoset (Callithrix jacchus), an early divergent in anthropoid evolution from humans, apes, and macaques. We generated atlases of the marmoset fovea and peripheral retina for both neonates and adults. Our comparative analysis revealed that marmosets share almost all its foveal types with both humans and macaques, highlighting a conserved cellular structure among primate foveas. Furthermore, by tracing the developmental trajectory of cell types in the foveal and peripheral retina, we found distinct maturation paths for each. In-depth analysis of gene expression differences demonstrated that cone photoreceptors and Müller glia, among others, show the greatest molecular divergence between these two regions. Utilizing single-cell ATAC-seq and gene-regulatory network inference, we uncovered distinct transcriptional regulations differentiating foveal cones from their peripheral counterparts. Further analysis of predicted ligand-receptor interactions suggested a potential role for Müller glia in supporting the maturation of foveal cones. Together, these results provide valuable insights into foveal development, structure, and evolution.<br><br>SIGNIFICANCE STATEMENT: The sharpness of our eyesight hinges on a tiny retinal region known as the fovea. The fovea is pivotal for primate vision and is susceptible to diseases like age-related macular degeneration. We studied the fovea in the marmoset-a primate with ancient evolutionary ties. Our data illustrated the cellular and molecular composition of its fovea across different developmental ages. Our findings highlighted a profound cellular consistency among marmosets, humans, and macaques, emphasizing the value of marmosets in visual research and the study of visual diseases.},
}
@article {pmid38105914,
year = {2023},
author = {Sayah, DN and Garg, I and Katz, R and Zhu, Y and Cui, Y and Zeng, R and Tandias, R and Moon, JY and Vingopoulos, F and Wescott, HE and Baldwin, G and Wang, K and Elze, T and Ludwig, CA and Vavvas, DG and Miller, JW and Husain, D and Kim, LA and Patel, NA and Miller, JB},
title = {Characterizing Macular Neovascularization in Myopic Macular Degeneration and Age-Related Macular Degeneration Using Swept Source OCTA.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {3855-3866},
pmid = {38105914},
issn = {1177-5467},
support = {P30 EY003790/EY/NEI NIH HHS/United States ; R01 EY030088/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Visual prognosis and treatment burden for macular neovascularization (MNV) can differ between myopic macular degeneration (MMD) and age-related macular degeneration (AMD). We describe and compare MNV associated with MMD and AMD using swept-source (SS)-OCTA.<br><br>PATIENTS AND METHODS: Adult patients with documented MNV associated with MMD or AMD were consecutively recruited. Qualitative and quantitative features were assessed from 6x6mm angiograms, including the MNV area and vessel density (VD). Descriptive statistics and linear regression analyses were carried out.<br><br>RESULTS: Out of 75 enrolled eyes with diagnosed MNV (30 MMD-MNV and 45 AMD-MNV; mean age 55&#xb1;19 and 75&#xb1;8 years, respectively), 44 eyes had discernible MNV (11 MMD-MNV and 33 AMD-MNV) on SS-OCTA at the time of the study and were included in the analysis. The MMD-MNV group exhibited a three-fold smaller sized MNV (p=0.001), lower greatest linear dimension (p=0.009) and greatest vascular caliber (p<0.001) compared to AMD-MNVs, and had a higher prevalence of tree-in-bud pattern. Eyes with AMD showed a higher prevalence of type 1 MNVs with medusa pattern. There was no difference in the location of the MNV, shape's regularity, margins, presence of core vessel, capillary fringe, peripheral loops, or perilesional dark halo (p>0.05) between both conditions. After adjustment, decreased MNV area and increased VD were associated with the tree-in-bud pattern, whereas the diagnosis did not significantly influence those parameters.<br><br>CONCLUSION: While larger studies are warranted, this study is the first to describe and compare MMD-MNV and AMD-MNV using SS-OCTA, providing relevant clinical insight on MNV secondary to MMD and AMD. These findings also further validate OCTA as a powerful tool to detect and characterize MNV non-invasively.},
}
@article {pmid38105897,
year = {2023},
author = {Xia, X and Guo, X},
title = {Adeno-associated virus vectors for retinal gene therapy in basic research and clinical studies.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1310050},
pmid = {38105897},
issn = {2296-858X},
abstract = {Retinal degenerative diseases, including glaucoma, age-related macular degeneration, diabetic retinopathy, and a broad range of inherited retinal diseases, are leading causes of irreversible vision loss and blindness. Gene therapy is a promising and fast-growing strategy to treat both monogenic and multifactorial retinal disorders. Vectors for gene delivery are crucial for efficient and specific transfer of therapeutic gene(s) into target cells. AAV vectors are ideal for retinal gene therapy due to their inherent advantages in safety, gene expression stability, and amenability for directional engineering. The eye is a highly compartmentalized organ composed of multiple disease-related cell types. To determine a suitable AAV vector for a specific cell type, the route of administration and choice of AAV variant must be considered together. Here, we provide a brief overview of AAV vectors for gene transfer into important ocular cell types, including retinal pigment epithelium cells, photoreceptors, retinal ganglion cells, Müller glial cells, ciliary epithelial cells, trabecular meshwork cells, vascular endothelial cells, and pericytes, via distinct injection methods. By listing suitable AAV vectors in basic research and (pre)clinical studies, we aim to highlight the progress and unmet needs of AAV vectors in retinal gene therapy.},
}
@article {pmid38104944,
year = {2024},
author = {Nguyen, C and Saint-Pol, J and Dib, S and Pot, C and Gosselet, F},
title = {25-Hydroxycholesterol in health and diseases.},
journal = {Journal of lipid research},
volume = {65},
number = {1},
pages = {100486},
pmid = {38104944},
issn = {1539-7262},
mesh = {Animals ; *Hydroxycholesterols/metabolism ; Cholesterol/metabolism ; *Oxysterols ; Biological Transport ; Lipoproteins/metabolism ; Mammals/metabolism ; },
abstract = {Cholesterol is an essential structural component of all membranes of mammalian cells where it plays a fundamental role not only in cellular architecture, but also, for example, in signaling pathway transduction, endocytosis process, receptor functioning and recycling, or cytoskeleton remodeling. Consequently, intracellular cholesterol concentrations are tightly regulated by complex processes, including cholesterol synthesis, uptake from circulating lipoproteins, lipid transfer to these lipoproteins, esterification, and metabolization into oxysterols that are intermediates for bile acids. Oxysterols have been considered for long time as sterol waste products, but a large body of evidence has clearly demonstrated that they play key roles in central nervous system functioning, immune cell response, cell death, or migration and are involved in age-related diseases, cancers, autoimmunity, or neurological disorders. Among all the existing oxysterols, this review summarizes basic as well as recent knowledge on 25-hydroxycholesterol which is mainly produced during inflammatory or infectious situations and that in turn contributes to immune response, central nervous system disorders, atherosclerosis, macular degeneration, or cancer development. Effects of its metabolite 7α,25-dihydroxycholesterol are also presented and discussed.},
}
@article {pmid38104545,
year = {2024},
author = {Leroux, P and Agard, E and Billant, J and Levron, A and Bouvarel, H and Badri, Y and Douma, I and Pradat, P and Dot, C},
title = {Long Intervals between Intravitreal Injections Using a Treat-and-Extend Protocol in a Real-Life Context in AMD: The LIRE Study.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {247},
number = {1},
pages = {44-57},
pmid = {38104545},
issn = {1423-0267},
mesh = {Humans ; *Ranibizumab ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Treatment Outcome ; },
abstract = {INTRODUCTION: The aim of the study was to assess the outcome of long treat-and-extend (TE) anti-VEGF intravitreal injection (IVI) intervals (≥every 12 weeks [Q12W]) in neovascular age-related macular degeneration (nAMD). The aims of this retrospective study were to determine the proportion of nAMD eyes treated ≥ Q12W, to analyze their longitudinal, functional, and anatomical outcomes, and to compare functional and anatomical outcomes between eyes that rapidly versus slowly reached a Q12W regimen and between eyes directly treated with versus initiating lately the TE regimen.<br><br>METHODS: All patients receiving IVIs for nAMD were screened. The longitudinal, functional, and anatomical characteristics of Q12W-treated eyes were reported at different timepoints.<br><br>RESULTS: Ninety-one eyes were included (38% of our total nAMD cohort). The mean TE regimen time to reach a Q12W interval was 20.1 &#xb1; 16.2 months. During this time, a mean number of 12.1 &#xb1; 9.3 IVIs were needed. The mean best-corrected visual acuity was 68 letters at the time of diagnosis and was maintained (p > 0.05). Eyes that rapidly reached a Q12W interval had a shorter follow-up before TE regimen initiation (p = 0.04) and received fewer IVIs (p = 0.02) than eyes that slowly reached a Q12W interval. Eyes directly treated with the TE regimen reached a Q12W interval more rapidly than eyes with late TE initiation. The neovascularization subtype was not a predictor of outcome in TE-treated eyes.<br><br>CONCLUSION: &#x2265;Q12W eyes represent an important part of the nAMD population in our real-life study. No baseline anatomical characteristics were associated with the outcome under a TE regimen, although early TE regimen initiation allowed extending more rapidly the IVI interval.},
}
@article {pmid38104330,
year = {2023},
author = {Proctor, JG},
title = {Pentosan polysulfate and a pigmentary maculopathy: causation versus correlation?.},
journal = {The Canadian journal of urology},
volume = {30},
number = {6},
pages = {11732-11739},
pmid = {38104330},
issn = {1488-5581},
mesh = {Humans ; Pentosan Sulfuric Polyester/adverse effects ; *Macular Degeneration/chemically induced/complications ; *Cystitis, Interstitial/chemically induced/complications ; Pain ; Inflammation ; },
abstract = {INTRODUCTION: Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S. Food and Drug Administration approved oral medication for the treatment of IC pain and symptoms. Recently, articles described a pigmentary maculopathy in IC patients on long term PPS therapy. Currently, there is no definitive study directly linking PPS as the cause of the pigmentary maculopathy. The aim of this review is to evaluate if PPS is the causative factor of the pigmentary maculopathy or if PPS use is only associated with the pigmentary maculopathy.<br><br>MATERIALS AND METHODS: A comprehensive review of peer reviewed journals using the search terms IC, maculopathy, mast cells, immune inflammatory components, Tamm-Horsfall protein, cations and tight junctions was performed to examine the pathophysiology and role of chronic inflammation in IC and known retinal maculopathies.<br><br>RESULTS: Chronic inflammatory cells have been reported in age-related macular degeneration choroid blood vessels and in bladder submucosal and detrusor layers in IC patients. Studies in IC and maculopathies demonstrate a significant milieu of activated chronic inflammatory and immunologic responses that cause a more "leaky" epithelium and a subsequent cascade of inflammatory events that results in the pathological changes seen in these two conditions.<br><br>CONCLUSIONS: After an analysis of the literature describing a pigmentary maculopathy in IC patients on long term PPS, a causal relationship does not appear to be present. An alternate model is proposed postulating that the causative factor for the pigmentary maculopathy is the underlying inflammatory state associated with IC and not PPS use.},
}
@article {pmid38102473,
year = {2024},
author = {Chandra, S and Gurudas, S and Pearce, I and Mckibbin, M and Kotagiri, A and Menon, G and Burton, BJL and Talks, J and Grabowska, A and Ghanchi, F and Gale, R and Giani, A and Chong, V and Chen, CNT and Nicholson, L and Thottarath, S and Chandak, S and Sivaprasad, S},
title = {Baseline characteristics of eyes with early residual fluid post loading phase of aflibercept therapy in neovascular AMD: PRECISE study report 3.},
journal = {Eye (London, England)},
volume = {38},
number = {7},
pages = {1301-1307},
pmid = {38102473},
issn = {1476-5454},
support = {SIVS 1045//Boehringer Ingelheim/ ; SIVS1045//Boehringer Ingelheim/ ; },
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Male ; Female ; *Intravitreal Injections ; Aged ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Tomography, Optical Coherence ; *Subretinal Fluid ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; *Visual Acuity/physiology ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; ROC Curve ; Middle Aged ; },
abstract = {PURPOSE: To compare the baseline characteristics in patients with and without early residual fluid (ERF) after aflibercept loading phase (LP) in patients with treatment naïve neovascular age related macular degeneration (nAMD).<br><br>METHODS: Patients with nAMD initiated on LP of three intravitreal aflibercept doses were recruited from December 2019 to August 2021. Baseline demographic and OCT features associated with any ERF were analysed using Generalised Estimating Equations to account for inter-eye correlation. Receiver operating characteristic (ROC) curve was performed for selection of CST threshold.<br><br>RESULTS: Of 2128 patients enrolled, 1999 eyes of 1862 patients with complete data were included. After LP, ERF was present in 1000 (50.0%), eSRF in 746(37.3%) and eIRF in 428 (21.4%) eyes. In multivariable analysis of baseline features, eyes with increased central subfield thickness (CST) (OR 1.31 per 100 microns increase [95% CI 1.22 to 1.41]; P&#x2009;<&#x2009;0.001), eyes with IRF and SRF at baseline (1.62 [95% CI 1.17 to 2.22]; P&#x2009;=&#x2009;0.003), and those with SRF only (OR 2.26 [95% CI 1.59 to 3.20]; P&#x2009;<&#x2009;0.001) relative to IRF only were determinants of ERF. CST&#x2009;&#x2265;&#x2009;418 microns had 57% sensitivity and 58% specificity to distinguish ERF from no ERF at visit 4.<br><br>CONCLUSION: On average, 50% of eyes have ERF after aflibercept LP. Clinically relevant baseline determinants of ERF include CST&#x2009;&#x2265;&#x2009;418&#x2009;&#xb5; and presence of only SRF. These eyes may require further monthly treatment before extending treatment intervals.},
}
@article {pmid38101587,
year = {2024},
author = {Noh, SE and Lee, SJ and Cho, CS and Jo, DH and Park, KS and Kim, JH},
title = {Mitochondrial transplantation attenuates oligomeric amyloid-beta-induced mitochondrial dysfunction and tight junction protein destruction in retinal pigment epithelium.},
journal = {Free radical biology &amp; medicine},
volume = {212},
number = {},
pages = {10-21},
doi = {10.1016/j.freeradbiomed.2023.12.012},
pmid = {38101587},
issn = {1873-4596},
mesh = {Mice ; Animals ; *Retinal Pigment Epithelium/metabolism ; Tight Junction Proteins/metabolism ; Amyloid beta-Peptides/genetics/metabolism ; Mitochondria/metabolism ; *Mitochondrial Diseases/metabolism ; },
abstract = {Transplantation of mitochondria derived from mesenchymal stem cells (MSCs) has emerged as a new treatment method to improve mitochondrial dysfunction and alleviate cell impairment. Interest in using extrinsic mitochondrial transplantation as a therapeutic approach has been increasing because it has been confirmed to be effective in treating various diseases related to mitochondrial dysfunction, including ischemia, cardiovascular disease, and toxic damage. To support this application, we conducted an experiment to deliver external mitochondria to retinal pigment epithelial cells treated with oligomeric amyloid-beta (oAβ). Externally delivered amyloid-beta internalizes into cells and interacts with mitochondria, resulting in mitochondrial dysfunction and intracellular damage, including increased reactive oxygen species and destruction of tight junction proteins. Externally delivered mitochondria were confirmed to alleviate mitochondrial dysfunction and tight junction protein disruption as well as improve internalized oAβ clearance. These results were also confirmed in a mouse model in vivo. Overall, these findings indicate that the transfer of external mitochondria isolated from MSCs has potential as a new treatment method for age-related macular degeneration, which involves oAβ-induced changes to the retinal pigment epithelium.},
}
@article {pmid38098608,
year = {2023},
author = {Nadeem, A and Malik, IA and Shariq, F and Afridi, EK and Taha, M and Raufi, N and Naveed, AK and Iqbal, J and Habte, A},
title = {Advancements in the treatment of geographic atrophy: focus on pegcetacoplan in age-related macular degeneration.},
journal = {Annals of medicine and surgery (2012)},
volume = {85},
number = {12},
pages = {6067-6077},
pmid = {38098608},
issn = {2049-0801},
abstract = {Geographic atrophy (GA) is a progressive form of age-related macular degeneration characterized by the degeneration of retinal pigment epithelial cells and photoreceptor death. The dysregulation of the complement cascade has been implicated in GA progression. This review provides a comprehensive overview of the pathophysiology of age-related macular degeneration and GA, discusses current therapeutic options, and focuses on the recent breakthrough drug, pegcetacoplan (SYFOVRE). Pegcetacoplan is a complement inhibitor that selectively targets the C3 complement protein, effectively modulating complement activation. Clinical trials, including the OAKS and DERBY studies, have demonstrated the efficacy of SYFOVRE in reducing the growth of GA lesions compared to placebo. The FDA approval of SYFOVRE as the first and only definitive therapy for GA marks a significant milestone in the management of this debilitating condition. The review also explores potential future treatment strategies, including immune-modulating agents and ocular gene therapy. While SYFOVRE offers new hope for GA patients, further research is needed to evaluate its long-term benefits, safety profile, and optimal treatment regimens.},
}
@article {pmid38097811,
year = {2023},
author = {Li, C and Lum, F and Chen, EM and Collender, PA and Head, JR and Khurana, RN and Cunningham, ET and Moorthy, RS and Parke, DW and McLeod, SD},
title = {Shifts in ophthalmic care utilization during the COVID-19 pandemic in the US.},
journal = {Communications medicine},
volume = {3},
number = {1},
pages = {181},
pmid = {38097811},
issn = {2730-664X},
abstract = {BACKGROUND: Healthcare restrictions during the COVID-19 pandemic, particularly in ophthalmology, led to a differential underutilization of care. An analytic approach is needed to characterize pandemic health services usage across many conditions.<br><br>METHODS: A common analytical framework identified pandemic care utilization patterns across 261 ophthalmic diagnoses. Using a United States eye care registry, predictions of utilization expected without the pandemic were established for each diagnosis via models trained on pre-pandemic data. Pandemic effects on utilization were estimated by calculating deviations between observed and expected patient volumes from January 2020 to December 2021, with two sub-periods of focus: the hiatus (March-May 2020) and post-hiatus (June 2020-December 2021). Deviation patterns were analyzed using cluster analyses, data visualizations, and hypothesis testing.<br><br>RESULTS: Records from 44.62 million patients and 2455 practices show lasting reductions in ophthalmic care utilization, including visits for leading causes of visual impairment (age-related macular degeneration, diabetic retinopathy, cataract, glaucoma). Mean deviations among all diagnoses are 67% below expectation during the hiatus peak, and 13% post-hiatus. Less severe conditions experience greater utilization reductions, with heterogeneities across diagnosis categories and pandemic phases. Intense post-hiatus reductions occur among non-vision-threatening conditions or asymptomatic precursors of vision-threatening diseases. Many conditions with above-average post-hiatus utilization pose a risk for irreversible morbidity, such as emergent pediatric, retinal, or uveitic diseases.<br><br>CONCLUSIONS: We derive high-resolution insights on pandemic care utilization in the US from high-dimensional data using an analytical framework that can be applied to study healthcare disruptions in other settings and inform efforts to pinpoint unmet clinical needs.},
}
@article {pmid38097101,
year = {2024},
author = {Wang, C and Li, X and Su, J and Duan, J and Yao, Y and Shang, Q},
title = {Crocetin inhibits choroidal neovascularization in both in vitro and in vivo models.},
journal = {Experimental eye research},
volume = {238},
number = {},
pages = {109751},
doi = {10.1016/j.exer.2023.109751},
pmid = {38097101},
issn = {1096-0007},
mesh = {Mice ; Animals ; Humans ; *Endothelial Cells/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Sincalide/metabolism ; *Choroidal Neovascularization/drug therapy/prevention &amp; control/metabolism ; Hypoxia/metabolism ; Disease Models, Animal ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1β, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.},
}
@article {pmid38095690,
year = {2024},
author = {Sotani, R and Matsumiya, W and Kim, KW and Miki, A and Yasuda, E and Maeda, Y and Hara, R and Kusuhara, S and Nakamura, M},
title = {Correction: Clinical features and associated factors of intraocular inflammation following intravitreal brolucizumab as switching therapy for neovascular age‑related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {2},
pages = {671},
doi = {10.1007/s00417-023-06339-z},
pmid = {38095690},
issn = {1435-702X},
}
@article {pmid38095375,
year = {2023},
author = {Kırıkkaya, E and Kaynak, S},
title = {Role of OCTA in the prognosis of dry-type AMD.},
journal = {European review for medical and pharmacological sciences},
volume = {27},
number = {23},
pages = {11264-11274},
doi = {10.26355/eurrev_202312_34565},
pmid = {38095375},
issn = {2284-0729},
mesh = {Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Fluorescein Angiography/methods ; *Retinal Vessels ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Visual Acuity ; Prognosis ; },
abstract = {OBJECTIVE: This study aimed to determine the prognostic value of Optical Coherence Tomography Angiography (OCTA) in dry-type age-related macular degeneration (AMD).<br><br>PATIENTS AND METHODS: Thirty-five eyes of 25 patients with dry-type AMD were included in the study. All patients underwent a complete ophthalmological examination. First and last foveal avascular zone (FAZ), foveal density (FD), FAZ perimeter, non-flow area (NFA), foveal (F)-parafoveal-perifoveal superficial and deep capillary plexus (SCP-DCP) vessel density (VD) OCTA measurements were recorded. Foveal thickness (FT), macular volume (MV), and choroidal thickness (CT) measurements with enhanced depth imaging (EDI) mode were made with Optical Coherence Tomography (OCT). The relationship of all parameters with the best corrected visual acuity (BCVA-logmar) was evaluated. A p-value <0.05 was considered statistically significant.<br><br>RESULTS: The mean age of the patients was 73.3&#xb1;11.8 (45-91) years. There was a statistically significant difference between the first and last BCVA, FT, and FD. While FD and BCVA increased, FT was found to decrease statistically significant (p=0.002, p=0.001, p=0.045, respectively). The correlation of BCVA with other variables at the first and last visit was examined. There was a statistically positive correlation between BCVA and FAZ, FAZ perimeter, and NFA in the first and last measurements. In the second measurement, a statistically negative correlation was found between BCVA and MV, FT, superficial FVD, superficial FT, deep FT, superficial parafoveal VD, superficial parafoveal FT, deep parafoveal FT, deep parafoveal VD, and FD variables.<br><br>CONCLUSIONS: There are positive and negative correlations between OCTA parameters and BCVA in the SCP-DCP in dry-type AMD. OCTA has prognostic significance in dry AMD.},
}
@article {pmid38094254,
year = {2023},
author = {Brown, KC and Light, RS and Modi, KJ and Conely, KB and Sugrue, AM and Cox, AJ and Miles, SL and Valentovic, MA and Dasgupta, P},
title = {An Improved Protocol for the Matrigel Duplex Assay: A Method to Measure Retinal Angiogenesis.},
journal = {Bio-protocol},
volume = {13},
number = {23},
pages = {e4899},
pmid = {38094254},
issn = {2331-8325},
support = {P20 GM103434/GM/NIGMS NIH HHS/United States ; R15 CA161491/CA/NCI NIH HHS/United States ; R15 HL145573/HL/NHLBI NIH HHS/United States ; },
abstract = {Neovascular diseases of the retina, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), are proliferative retinopathies involving the growth of new blood vessels on the retina, which in turn causes impairment and potential loss of vision. A drawback of conventional angiogenesis assays is that they are not representative of the angiogenic processes in the retina. In the retina, the new blood vessels grow (from pre-existing blood vessels) and migrate into a non-perfused region of the eye including the inner limiting membrane of the retina and the vitreous, both of which contribute to vision loss. The Matrigel Duplex Assay (MDA) measures the migration of angiogenic capillaries from a primary Matrigel layer to a secondary Matrigel layer, which resembles the pathological angiogenesis in AMD and DR. The methodology of MDA is comprised of two steps. In the first step, the human retinal microvascular endothelial cells (HRMECs) are mixed with phenol red-containing Matrigel (in a 1:1 ratio) and seeded in the center of an 8-well chamber slide. After 24 h, a second layer of phenol red-free Matrigel is overlaid over the first layer. Over the course of the next 24 h, the HRMECs invade from the primary Matrigel layer to the secondary layer. Subsequently, the angiogenic sprouts are visualized by brightfield phase contrast microscopy and quantified by ImageJ software. The present manuscript measures the angiogenesis-inhibitory activity of the Src kinase inhibitor PP2 in primary HRMECs using the MDA. The MDA may be used for multiple applications like screening anti-angiogenic drugs, measuring the pro-angiogenic activity of growth factors, and elucidating signaling pathways underlying retinal angiogenesis in normal and disease states.},
}
@article {pmid38093557,
year = {2024},
author = {Lee, K and Park, YM and Choi, JK and Lee, J},
title = {Impact of COVID-19 on ophthalmic medical access during successive waves: Demographics, disease factors, and wave locations.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {4},
pages = {387-401},
doi = {10.1111/ceo.14340},
pmid = {38093557},
issn = {1442-9071},
support = {NHIMC-2021-PR-029//National Health Insurance Service Ilsan Hospital/ ; },
mesh = {Humans ; *COVID-19/epidemiology ; Female ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Aged ; *SARS-CoV-2 ; *Eye Diseases/epidemiology ; Adult ; Health Services Accessibility/statistics &amp; numerical data ; Ophthalmology/statistics &amp; numerical data ; Pandemics ; Aged, 80 and over ; Young Adult ; Adolescent ; Retrospective Studies ; Incidence ; },
abstract = {BACKGROUND: The coronavirus disease (COVID-19) pandemic significantly impacted medical care, including ophthalmology. This study aimed to identify factors associated with reduced ophthalmic medical access during the pandemic.<br><br>METHODS: This nationwide population-based cohort study analysed South Korean health insurance claims data from January 2019 to November 2021. Outpatient visits and surgeries for age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and retinal detachment during the two pandemic waves were compared with those in the non-pandemic period. Poisson regression was used to estimate incidence rate ratios and changes in outpatient visits and surgeries between waves concerning patient age, sex, residential location, and health insurance type.<br><br>RESULTS: Outpatient visits for five eye diseases decreased in the first wave (0.733-0.985, P&#x2009;<&#x2009;0.001). In the second wave, only outpatient visits for age-related macular degeneration, cataract, and glaucoma decreased (0.754, 0.878, and 0.874, respectively, all P&#x2009;<&#x2009;0.001). Age-related macular degeneration, cataract, and glaucoma surgeries were significantly reduced in the first wave (0.829, P&#x2009;<&#x2009;0.001; 0.836, P&#x2009;<&#x2009;0.001; 0.904, P&#x2009;=&#x2009;0.030, respectively). Age-related macular degeneration (0.852) and cataract (0.716) surgeries dropped in the second wave. Women and elderly (>65&#x2009;years) patients curtailed outpatient visits and surgeries more throughout the pandemic and were less resilient during the second wave. Wave location was also related to outpatient visits and surgeries.<br><br>CONCLUSIONS: The COVID-19 pandemic decreased outpatient visits and surgeries for eye diseases, with more significant impact on women, older patients, and those residing near wave locations. These findings can inform healthcare policies to minimise future pandemic impacts on healthcare delivery.},
}
@article {pmid38092820,
year = {2023},
author = {Pundlik, S and Shivshanker, P and Nigalye, A and Luo, G and Husain, D},
title = {Evaluation of a mobile app for dark adaptation measurement in individuals with age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {22191},
pmid = {38092820},
issn = {2045-2322},
support = {R01 EY030088/EY/NEI NIH HHS/United States ; R21 EY029847/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Aged ; Middle Aged ; Dark Adaptation ; *Mobile Applications ; Visual Acuity ; Cross-Sectional Studies ; *Macular Degeneration ; },
abstract = {We present clinical evaluation of a mobile app for dark adaptation (DA) measurement in age-related macular degeneration (AMD) patients and in older adults (age > 50 years) without AMD or other retinal disorders (NV). The outcome measures were the area under dark adaptation curve (AUDAC) and the time for visual sensitivity to recover by 3 log units (TR). Larger AUDAC and TR values indicated worse DA response. The association of AUDAC with AMD was analyzed using linear regression, while time-to-event analysis was used for TR. 32 AMD patients (mean ± SD; age:72 ± 6.3 years, VA:0.09 ± 0.08 logMAR) and 25 NV subjects (mean ± sd; age:65 ± 8.7 years, VA:0.049 ± 0.07 logMAR) were measured with the app. Controlling for age, VA, and cataract severity, the AMD presence was significantly associated with higher AUDAC (β = 0.41, 95% CI 0.18-0.64, p = 0.001) and with slower sensitivity recovery (β = 0.32, 95% CI 0.15-0.69, p = 0.004). DA measurements with the app were highly correlated with those obtained with AdaptDx-an established clinical device (n = 18, ρ = 0.87, p < 0.001). AMD classification accuracy using the app was 72%, which was comparable to the 71% accuracy of AdaptDx. Our findings indicate that the mobile app provided reliable and clinically meaningful DA measurements that were strongly correlated with the current standard of care in AMD.},
}
@article {pmid38092262,
year = {2024},
author = {Zhang, SX and Wang, JJ and Starr, CR and Lee, EJ and Park, KS and Zhylkibayev, A and Medina, A and Lin, JH and Gorbatyuk, M},
title = {The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.},
journal = {Progress in retinal and eye research},
volume = {98},
number = {},
pages = {101231},
pmid = {38092262},
issn = {1873-1635},
support = {R01 EY034110/EY/NEI NIH HHS/United States ; R01 EY027763/EY/NEI NIH HHS/United States ; R01 EY019949/EY/NEI NIH HHS/United States ; I01 RX002340/RX/RRD VA/United States ; R01 EY030970/EY/NEI NIH HHS/United States ; I01 BX002284/BX/BLRD VA/United States ; R21 EY025061/EY/NEI NIH HHS/United States ; R01 NS088485/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Retinal Degeneration/metabolism ; *Diabetic Retinopathy/metabolism ; Unfolded Protein Response ; Endoplasmic Reticulum Stress/physiology ; Retina ; Endoplasmic Reticulum/metabolism ; Homeostasis/physiology ; },
abstract = {The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding, and trafficking, lipid and sterol biosynthesis, carbohydrate metabolism, and calcium storage and gated release. In addition, the ER makes close contact with multiple intracellular organelles such as mitochondria and the plasma membrane to actively regulate the biogenesis, remodeling, and function of these organelles. Therefore, maintaining a homeostatic and functional ER is critical for the survival and function of cells. This vital process is implemented through well-orchestrated signaling pathways of the unfolded protein response (UPR). The UPR is activated when misfolded or unfolded proteins accumulate in the ER, a condition known as ER stress, and functions to restore ER homeostasis thus promoting cell survival. However, prolonged activation or dysregulation of the UPR can lead to cell death and other detrimental events such as inflammation and oxidative stress; these processes are implicated in the pathogenesis of many human diseases including retinal disorders. In this review manuscript, we discuss the unique features of the ER and ER stress signaling in the retina and retinal neurons and describe recent advances in the research to uncover the role of ER stress signaling in neurodegenerative retinal diseases including age-related macular degeneration, inherited retinal degeneration, achromatopsia and cone diseases, and diabetic retinopathy. In some chapters, we highlight the complex interactions between the ER and other intracellular organelles focusing on mitochondria and illustrate how ER stress signaling regulates common cellular stress pathways such as autophagy. We also touch upon the integrated stress response in retinal degeneration and diabetic retinopathy. Finally, we provide an update on the current development of pharmacological agents targeting the UPR response and discuss some unresolved questions and knowledge gaps to be addressed by future research.},
}
@article {pmid38091605,
year = {2025},
author = {Battaglia Parodi, M and Antropoli, A and Arrigo, A and Cicinelli, MV and Bianco, L and Saladino, A and Moretti, E and Bandello, F and Mansour, A},
title = {ACUTE ATROPHIC EVOLUTION OF DRUSENOID PIGMENT EPITHELIUM DETACHMENT AFTER PHOTOBIOMODULATION.},
journal = {Retinal cases &amp; brief reports},
volume = {19},
number = {2},
pages = {225-227},
doi = {10.1097/ICB.0000000000001529},
pmid = {38091605},
issn = {1937-1578},
mesh = {Humans ; Acute Disease ; Atrophy/etiology ; Fluorescein Angiography ; *Low-Level Light Therapy/adverse effects ; *Macular Degeneration/radiotherapy ; *Retinal Detachment/etiology/diagnosis ; *Retinal Drusen/etiology/diagnosis ; *Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence ; Visual Acuity ; },
abstract = {PURPOSE: The aim of this study was to report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration.<br><br>METHODS: Optical coherence tomography was performed in the study eye before and after PBM.<br><br>RESULTS: A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM, the D-PED collapsed, resulting in complete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening.<br><br>CONCLUSION: Thinning of the outer retinal layers over a D-PED and posterior hypertransmission may represent bad prognostic factors for PBM, accelerating the lesion's natural history toward atrophic evolution.},
}
@article {pmid38089520,
year = {2023},
author = {Ou, YC and Cheng, CK and Yang, CS},
title = {Retinal pigment epithelium tear in an idiopathic acute onset bullous central serous chorioretinopathy.},
journal = {Taiwan journal of ophthalmology},
volume = {13},
number = {3},
pages = {389-392},
pmid = {38089520},
issn = {2211-5072},
abstract = {Although retinal pigment epithelium (RPE) tears are common in patients with chronic conditions such as exudative age-related macular degeneration or may occur in response to anti-vascular endothelial growth factor or laser treatment, a spontaneous RPE tear can occur in patients with acute and new-onset bullous central serous chorioretinopathy (CSCR). We present a rare case of a healthy young Asian man with unilateral massive subretinal fluid (SRF). An idiopathic acute-onset bullous CSCR with an RPE tear was diagnosed through ancillary examinations. This patient exhibited good visual recovery as indicated by foveal sparing, spontaneous resolution of SRF, and the lack of a need for unnecessary surgery.},
}
@article {pmid38088362,
year = {2024},
author = {Heger, KA and Waldstein, SM},
title = {Artificial intelligence in retinal imaging: current status and future prospects.},
journal = {Expert review of medical devices},
volume = {21},
number = {1-2},
pages = {73-89},
doi = {10.1080/17434440.2023.2294364},
pmid = {38088362},
issn = {1745-2422},
mesh = {Humans ; *Artificial Intelligence ; Retina/diagnostic imaging ; *Diabetic Retinopathy ; Tomography, Optical Coherence/methods ; Aging ; },
abstract = {INTRODUCTION: The steadily growing and aging world population, in conjunction with continuously increasing prevalences of vision-threatening retinal diseases, is placing an increasing burden on the global healthcare system. The main challenges within retinology involve identifying the comparatively few patients requiring therapy within the large mass, the assurance of comprehensive screening for retinal disease and individualized therapy planning. In order to sustain high-quality ophthalmic care in the future, the incorporation of artificial intelligence (AI) technologies into our clinical practice represents a potential solution.<br><br>AREAS COVERED: This review sheds light onto already realized and promising future applications of AI techniques in retinal imaging. The main attention is directed at the application in diabetic retinopathy and age-related macular degeneration. The principles of use in disease screening, grading, therapeutic planning and prediction of future developments are explained based on the currently available literature.<br><br>EXPERT OPINION: The recent accomplishments of AI in retinal imaging indicate that its implementation into our daily practice is likely to fundamentally change the ophthalmic healthcare system and bring us one step closer to the goal of individualized treatment. However, it must be emphasized that the aim is to optimally support clinicians by gradually incorporating AI approaches, rather than replacing ophthalmologists.},
}
@article {pmid38087257,
year = {2023},
author = {Guo, H and Li, J and Lu, P},
title = {Systematic review and meta-analysis of mass spectrometry proteomics applied to ocular fluids to assess potential biomarkers of age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {507},
pmid = {38087257},
issn = {1471-2415},
support = {CXTDA2017039//Jiangsu Provincial Medical Innovation Team/ ; 81671641, 82271113//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Proteomics ; *Macular Degeneration/genetics ; Biomarkers/metabolism ; Proteins ; Mass Spectrometry ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a significant cause of severe vision loss. The main purpose of this study was to identify mass spectrometry proteomics-based potential biomarkers of AMD that contribute to understanding the mechanisms of disease and aiding in early diagnosis.<br><br>METHODS: This study retrieved studies that aim to detect differences relate to proteomics in AMD patients and healthy control groups by mass spectrometry (MS) proteomics approaches. The search process was accord with PRISMA guidelines (PROSPERO database: CRD42023388093). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes Pathway Analysis (KEGG) were performed on differentially expressed proteins (DEPs) in the included articles using the DAVID database. DEPs were included in a meta-analysis when their effect size could be computed in at least two research studies. The effect size of measured proteins was transformed to the log2-fold change. Protein&#x2012;protein interaction (PPI) analysis was conducted on proteins that were statistically significant in the meta-analysis using the String online database.<br><br>RESULTS: Eleven studies fulfilled the inclusion criteria, and 161 DEPs were identified. The GO analysis showed that AMD is significantly related to proteolysis, extracellular exosome and protein binding. In KEGG, the most significant pathway was the complement and coagulation cascades. Meta-analysis results suggested that eight proteins were statistically significant, and according to PPI results, the most significant four proteins were serotransferrin (TF), apolipoprotein A1 (APOA1), complement C3 (C3) and lipocalin-1 (LCN1).<br><br>CONCLUSIONS: Four possible biomarkers, TF, APOA1, C3 and LCN1, were found to be significant in the pathogenesis of AMD and need to be further validated. Further studies should be performed to evaluate diagnostic and therapeutic value of these proteins.},
}
@article {pmid38087197,
year = {2023},
author = {Ryou, IS and Lee, SW and Mun, H and Lee, JK and Chun, S and Cho, K},
title = {Trend of incidence rate of age-related diseases: results from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database in Korea: a cross- sectional study.},
journal = {BMC geriatrics},
volume = {23},
number = {1},
pages = {840},
pmid = {38087197},
issn = {1471-2318},
support = {2021-20-014//National Health Insurance Service Ilsan Hospital Fund/ ; },
mesh = {Male ; Humans ; Aged ; Incidence ; *Pulmonary Disease, Chronic Obstructive ; *Hypertension ; *Heart Failure ; Aging ; *Cerebrovascular Disorders/diagnosis/epidemiology ; National Health Programs ; *Hearing Loss ; *Myocardial Ischemia ; Republic of Korea/epidemiology ; *Respiratory Distress Syndrome ; },
abstract = {BACKGROUND: This study aimed to identify and select age-related diseases (ARDs) in Korea, which is about to have a super-aged society, and to elucidate patterns in their incidence rates.<br><br>METHODS: The National Health Insurance Service-National Sample Cohort, comprising 1 million health insurance and medical benefit beneficiaries in Korea from 2002 to 2019, was utilized. We selected 14 diseases with high disease burden and prevalence among Koreans from the 92 diseases defined in the Global Burden of Diseases, Injuries, and Risk Factors Study as ARDs. The annual incidence rate represented the number of patients newly diagnosed with an ARD each year from 2006 to 2019, excluding those with a history of ARD diagnosis from 2002 to 2005. The incidence rate by age was categorized into 10-year units based on age as of 2019. The number of patients with ARDs in each age group was used as the numerator, and the incidence rate for each age group was calculated with the age group as the denominator.<br><br>RESULTS: Regarding the annual incidence rates of ARDs from 2006 to 2019, chronic obstructive pulmonary disease, congestive heart failure, and ischemic heart disease decreased annually, whereas dyslipidemia, chronic kidney disease, cataracts, hearing loss, and Parkinson's disease showed a significant increase. Hypertension, diabetes, cerebrovascular disease, osteoporosis, osteoarthritis, and age-related macular degeneration initially displayed a gradual decrease in incidence but exhibited a tendency to increase after 2015. Concerning age-specific incidence rates of ARDs, two types of curves emerged. The first type, characterized by an exponential increase with age, was exemplified by congestive heart failure. The second type, marked by an exponential increase peaking between ages 60 and 80, followed by stability or decrease, was observed in 13 ARDs, excluding congestive heart failure. However, hypertension, ischemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and hearing loss in men belonged to the first type.<br><br>CONCLUSIONS: From an epidemiological perspective, there are similar characteristics in age-specific ARDs that increase with age, reaching a peak followed by a plateau or decrease in Koreans.},
}
@article {pmid38085785,
year = {2023},
author = {Chen, Y and Bounds, SE and Ma, X and Karmoker, JR and Liu, Y and Ma, JX and Cai, J},
title = {Interleukin-17-mediated protective cytokine signaling against degeneration of the retinal pigment epithelium.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {51},
pages = {e2311647120},
pmid = {38085785},
issn = {1091-6490},
support = {R01 EY028773/EY/NEI NIH HHS/United States ; R01 EY034510/EY/NEI NIH HHS/United States ; R01 EY034742/EY/NEI NIH HHS/United States ; R01 EY028949/EY/NEI NIH HHS/United States ; P30 EY021725/EY/NEI NIH HHS/United States ; R01 EY026999/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Cytokines/metabolism ; Interleukin-17/genetics/metabolism ; *Macular Degeneration/pathology ; Retina/metabolism ; *Retinal Degeneration/metabolism ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury. In the current study, we employed single-cell RNA sequencing approach to characterize the profiles of immune cells in mouse choroid. We found that γδ T cells were the primary producer of interleukin-17 (IL-17) in the choroid. IL-17 signaled through its receptor on the RPE, subsequently triggering the production of interleukin-6. This cascade of cytokines initiated a metabolic reprogramming of subretinal microglia, enhancing their capacity for lipid metabolism. RPE-specific knockout of IL-17 receptor A led to the dysfunction of subretinal microglia and RPE pathology. Collectively, our findings suggest that responding to RPE injury, the choroidal γδ T cells can initiate a protective signaling cascade that ensures the proper functioning of subretinal microglia.},
}
@article {pmid38083157,
year = {2023},
author = {Ye, Z and Hang Chan, LL},
title = {Effect of the Aperiodic Electrical Stimulation on the Visual Cortical Neuronal Response.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2023},
number = {},
pages = {1-4},
doi = {10.1109/EMBC40787.2023.10341193},
pmid = {38083157},
issn = {2694-0604},
mesh = {Humans ; Rats ; Animals ; Rats, Sprague-Dawley ; *Retina/physiology ; Retinal Ganglion Cells/physiology ; *Visual Cortex/physiology ; Electric Stimulation ; },
abstract = {In patients with retinal degenerative illnesses such as retinitis pigmentosa and age-related macular degeneration, retinal prosthesis shows the potential to restore partial vision. The natural stimuli are the aperiodic events distributed across a short time span. However, most studies commonly used periodic stimulation. Even though some in vitro studies explored the effect of aperiodic retinal stimulation on the retina ganglion cells' membrane potential, it still needs to understand how the aperiodic electrical stimulation on the retina affects the response in visual cortex. This study investigated how aperiodic retinal stimulation affects the electrically evoked cortical response compared with periodic stimulation in Sprague Dawley (SD) rats. We found that the aperiodic retinal stimulation evoked a significantly higher spike rate than the periodic pattern, especially at high frequencies (10 and 20 Hz). The spike rates showed a more significant difference between the periodic and 10% noise stimulation (P = 0.0013 at 20 Hz, two-tailed paired t-test) at 20 Hz stimulation. Regarding the temporal precision of responses, the responses to aperiodic stimulation showed higher temporal precision compared to periodic stimulation. The response to some stimulation pulse numbers under 10 and 20 Hz 50% noise and Poisson pattern stimulation was higher than the response to the first pulse. However, at the same frequency, the response to some stimulation pulse numbers under periodic stimulation was lower than the response to the first pulse. These findings raised a possible way to increase the response level and the temporal precision of the electrically evoked response.Clinical Relevance- This suggests that using aperiodic stimulation in retinal prostheses can increase electrically evoked response levels and temporal precision.},
}
@article {pmid38074151,
year = {2023},
author = {Huang, KH and Chang, YL and Lee, CB and Gau, SY and Tsai, TH and Chung, NJ and Lee, CY},
title = {Dose-response association of metformin use and risk of age-related macular degeneration among patients with type 2 diabetes mellitus: a population-based study.},
journal = {Frontiers in pharmacology},
volume = {14},
number = {},
pages = {1275095},
pmid = {38074151},
issn = {1663-9812},
abstract = {Background: Recent studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) who receive metformin have a decreased risk of developing age-related macular degeneration (AMD). However, other studies have also suggested that metformin may increase the risk of AMD development. Therefore, this study investigated the association between treatment with metformin and the risk of AMD in patients with T2DM by using Taiwan' National Health Insurance Research Database. Methods: Patients who received a diagnosis of new-onset T2DM between 2002 and 2013 were enrolled in this study. The patients were divided into patients treated and not treated with metformin to evaluate the risk of AMD after 5 years of follow-up. The logistic regression was used to estimate the risk of AMD associated with the intensity of treatment with metformin. Result: A total of 7 517 patients (103.16 patients per 10,000 people) developed AMD in 5 years after DM diagnosis. After adjusting for the relevant variables, patients with T2DM treated with <5 defined daily dose (DDD)/month of metformin had a lower risk of AMD (odds ratios [OR]: 0.93; 95% confidence interval [CI]: 0.88 0.99). Patients treated with >25 DDD/month of metformin had a higher risk of AMD (OR: 1.39; 95% CI: 1.08-1.78). Conclusion: Metformin use may be associated with a risk of AMD among patients with T2DM in a dose-dependent association manner, with the greater benefit at lower DDD/month. However, higher DDD/month exhibited an increased risk of AMD.},
}
@article {pmid38072353,
year = {2024},
author = {Lin, L and Zheng, Y and Li, Q and Sun, Y and Huang, Y and Liang, L and Xu, L and Zhao, YE},
title = {Verteporfin regulates corneal neovascularization through inhibition of YAP protein activation.},
journal = {Experimental eye research},
volume = {238},
number = {},
pages = {109747},
doi = {10.1016/j.exer.2023.109747},
pmid = {38072353},
issn = {1096-0007},
mesh = {Animals ; Rats ; *Choroidal Neovascularization/drug therapy/metabolism ; *Corneal Neovascularization/drug therapy ; Endothelial Cells/metabolism ; Photosensitizing Agents/pharmacology/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; *Verteporfin/pharmacology/therapeutic use ; },
abstract = {Corneal neovascularization (CNV) is a vision-threatening disease that is becoming a growing public health concern. While Yes-associated protein (YAP) plays a critical role in neovascular disease and allow for the sprouting angiogenesis. Verteporfin (VP) is a classical inhibitor of the YAP-TEAD complex, which is used for clinical treatment of neovascular macular degeneration through photodynamic therapy. The purpose of this study is to explore the effect of verteporfin (VP) on the inhibition of CNV and its potential mechanism. Rat CNV model were established by suturing in the central cornea and randomly divided into three groups (control, CNV and VP group). Neovascularization was observed by slit lamp to extend along the corneal limbus to the suture line. RNA-sequencing was used to reveal the related pathways on the CNV and the results revealed the vasculature development process and genes related with angiogenesis in CNV. In CNV group, we detected the nuclear translocation of YAP and the expression of CD31 in corneal neovascular endothelial cells through immunofluorescence. After the application of VP, the proliferation, migration and the tube formation of HUVECs were significantly inhibited. Furthermore, VP showed the CNV inhibition by tail vein injection without photoactivation. Then we found that the expression of phosphorylated YAP significantly decreased, and its downstream target protein connective tissue growth factor (CTGF) increased in the CNV group, while the expression was just opposite in other groups. Besides, both the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and cofilin significantly increased in CNV group, and decreased after VP treatment. Therefore, we conclude that Verteporfin could significantly inhibited the CNV without photoactivation by regulating the activation of YAP.},
}
@article {pmid38071435,
year = {2024},
author = {Husum, YS and Bråten, RH and Sæther, EM and Moe, MC and Kristiansen, IS and Jørstad, &#xd8;K},
title = {Intravitreal anti-vascular endothelial growth factor therapy for retinal diseases in Norway from 2011 to 2021: A combined registry and survey study.},
journal = {Acta ophthalmologica},
volume = {102},
number = {5},
pages = {544-554},
doi = {10.1111/aos.16598},
pmid = {38071435},
issn = {1755-3768},
mesh = {Humans ; *Intravitreal Injections ; Norway/epidemiology ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Registries ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; Aged ; Female ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; Middle Aged ; Surveys and Questionnaires ; Retinal Diseases/drug therapy/epidemiology ; Retrospective Studies ; Ranibizumab/administration &amp; dosage ; Bevacizumab/administration &amp; dosage/therapeutic use ; Visual Acuity ; },
abstract = {PURPOSE: To investigate the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in Norway from 2011 to 2021 and explore how the eye departments organized their injection services.<br><br>METHODS: We combined data from the Norwegian Patient Registry (NPR) with survey responses from Norway's 22 eye departments. The NPR data encompassed all registered intravitreal injection episodes from 2011 to 2021. The survey contained questions about local treatment practices and emphasized neovascular age-related macular degeneration (nAMD), retinal vein occlusion and diabetic macular edema.<br><br>RESULTS: A total of 47247 unique patients received 841&#x2009;646 intravitreal injections in the study period. The number of patients per year increased from 6522 in 2011 to 20&#x2009;635 in 2021. The number of injections per year increased from 30&#x2009;926 in 2011 to 125&#x2009;258 in 2021. The most frequent diagnosis was nAMD. In 2021, the age-adjusted treatment activity in Norway's 11 counties ranged from 47.8 to 75.5 injections per 1000 inhabitants aged &#x2265;50&#x2009;years. The use of aflibercept gradually exceeded bevacizumab, but the aflibercept proportion per county ranged from 38 to 82% in 2021. The survey revealed varying treatment practices, local guidelines were often absent, and only half of the departments defined a lower visual limit for initiating or maintaining treatment.<br><br>CONCLUSION: The use of intravitreal anti-VEGF therapy increased considerably from 2011 to 2021, but there was considerable regional variation in treatment activity, drug utilization and organization of injection services. These findings emphasize the need for strengthened governance and national guidelines to ensure equal treatment nationally.},
}
@article {pmid38069616,
year = {2024},
author = {Kenworthy, MK and Alexis, JA and Ramakrishnan, P and Chen, FK},
title = {Retreatment interval lengthening achieved in two thirds of eyes with prolonged intensive anti-VEGF therapy for neovascular age-related macular degeneration after switching to faricimab.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {52},
number = {5},
pages = {589-591},
doi = {10.1111/ceo.14335},
pmid = {38069616},
issn = {1442-9071},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Visual Acuity/physiology ; *Retreatment ; *Ranibizumab/administration &amp; dosage/therapeutic use ; *Bevacizumab/administration &amp; dosage/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use/administration &amp; dosage ; Tomography, Optical Coherence ; Male ; Female ; Aged ; Retrospective Studies ; Drug Substitution ; Aged, 80 and over ; Fluorescein Angiography ; },
}
@article {pmid38069124,
year = {2023},
author = {Nishiyama, T and Tsujinaka, H and Ueda, T and Ogata, N},
title = {Alteration in Melanin Content in Retinal Pigment Epithelial Cells upon Hydroquinone Exposure.},
journal = {International journal of molecular sciences},
volume = {24},
number = {23},
pages = {},
pmid = {38069124},
issn = {1422-0067},
support = {20K18389//JSPS KAKENHI/ ; },
mesh = {*Melanins/metabolism ; *Hydroquinones/pharmacology ; Vascular Endothelial Growth Factor A/metabolism ; Retinal Pigment Epithelium/metabolism ; Epithelial Cells/metabolism ; },
abstract = {Abnormal pigmentation or depigmentation of the retinal pigment epithelium (RPE) is a precursor to neovascular age-related macular degeneration (nAMD). In this study, we evaluated the effects of hydroquinone (HQ), the most potent reductant in cigarette smoke, on the melanin production in RPE cells. Induced pluripotent stem cell (iPS)-derived RPE and adult retinal pigment epithelial (ARPE-19) cells were cultured with HQ. Real-time reverse transcription polymerase chain reaction revealed that the expression of melanin-related genes decreased due to the addition of HQ for 1 day. Enzyme-linked immunosorbent immunoassay showed that the concentration of melanin significantly decreased due to the addition of HQ for 24 h. A suspension of RPE cells with HQ for 24 h was prepared, and the absorbance was measured. The absorbance decreased particularly under blue light, suggesting that blue light may reach the choroid and cause choroidal inflammation. Additionally, melanin levels significantly decreased due to the addition of HQ for 1 week. After blue light irradiation on the RPE with HQ for 1 week, the vascular endothelial growth factor in the medium was significantly higher in the HQ group than in the control group. HQ-induced changes in melanin production may be responsible for the uneven pigmentation of the RPE, and these changes may cause nAMD.},
}
@article {pmid38068487,
year = {2023},
author = {Wolfram, C and Pfeiffer, N and Hudde, T and Klatt, A and Schnegelsberg, B and Ross, M and Ziemssen, F and Schuster, AK},
title = {The Psychological, Social and Behavioral Impact of Intravitreal Anti-VEGF Therapy: An Analysis from the ALBATROS Data.},
journal = {Journal of clinical medicine},
volume = {12},
number = {23},
pages = {},
pmid = {38068487},
issn = {2077-0383},
support = {0000 not able to provide a grant number at the moment//Novartis Pharma, Nuremberg, Germany/ ; },
abstract = {BACKGROUND: Retinal diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or branch/central retinal vein occlusion (B/CRVO) have significant implications for patients' social and psychological well-being. The ALBATROS study aimed to assess the care situation of patients who received anti-VEGF (vascular endothelial growth factor) treatment. To gain a comprehensive understanding of patients' backgrounds and attitudes, we developed an exploratory, structured questionnaire, the Basic Care and Patient Satisfaction Questionnaire (BPZ-9).<br><br>METHODS: The data collection took place at the beginning and after twelve months of anti-VEGF therapy. The BPZ-9 questionnaire comprises nine questions to evaluate patients' psychological and social situation and satisfaction with treatment.<br><br>RESULTS: Data were collected from 1478 nAMD (mean 78 years), 445 DME (67 years), 233 BRVO (70 years), and 144 CRVO (71 years) patients at 102 study centers throughout Germany. One in four patients had difficulties walking, and one in five needed an accompanying person for treatment. Anxiety about losing vision was present in three out of four patients at the beginning, and it slightly decreased to two out of three patients over the 12-month treatment period. The distress of having a retinal disease was generally higher than the distress related to the treatment. Most patients reported high treatment satisfaction (73%) and felt well-informed (81%).<br><br>CONCLUSIONS: There is a relevant social and psychological impact related to anti-VEGF treatment. The patients' perception, attitudes, and commitment need further investigation.},
}
@article {pmid38068454,
year = {2023},
author = {Matsubara, H and Nagashima, R and Chujo, S and Matsui, Y and Kato, K and Kuze, M and Kondo, M},
title = {Subclinical Ocular Changes after Intravitreal Injections of Different Anti-VEGF Agents for Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {23},
pages = {},
pmid = {38068454},
issn = {2077-0383},
abstract = {Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) after the initial intravitreal injection of aflibercept (IVA), brolucizumab (IVBr), or faricimab (IVF) for neovascular age-related macular degeneration (nAMD). The AFV and flicker ERGs were determined before, 2 weeks after, and 4 weeks after the injections in 14 eyes of 14 patients for each drug. After the injections, none of the patients had an IOI, but the AFV increased significantly in the IVA and IVF groups. The increase in the IVF group was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The implicit time was significantly prolonged in the IVBr group but unchanged in the IVA and IVF groups. These results suggest that brolucizumab, administered at high molar doses, may cause transient retinal disturbances that are not detectable by general ophthalmologic examinations but affect the implicit ERG times.},
}
@article {pmid38067097,
year = {2023},
author = {Shwani, T and Zhang, C and Owen, LA and Shakoor, A and Vitale, AT and Lillvis, JH and Barr, JL and Cromwell, P and Finley, R and Husami, N and Au, E and Zavala, RA and Graves, EC and Zhang, SX and Farkas, MH and Ammar, DA and Allison, KM and Tawfik, A and Sherva, RM and Li, M and Stambolian, D and Kim, IK and Farrer, LA and DeAngelis, MM},
title = {Patterns of Gene Expression, Splicing, and Allele-Specific Expression Vary among Macular Tissues and Clinical Stages of Age-Related Macular Degeneration.},
journal = {Cells},
volume = {12},
number = {23},
pages = {},
pmid = {38067097},
issn = {2073-4409},
support = {UL1TR0012-05/TR/NCATS NIH HHS/United States ; K08 EY031800/EY/NEI NIH HHS/United States ; 1K08EY031800-01/EY/NEI NIH HHS/United States ; R01 EY029751/EY/NEI NIH HHS/United States ; R01 EY031209/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Alleles ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Gene Expression ; Cytoskeletal Proteins ; Phosphate-Binding Proteins ; Carrier Proteins ; Nerve Tissue Proteins ; GTP-Binding Proteins ; *Serine-Type D-Ala-D-Ala Carboxypeptidase ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness, and elucidating its underlying disease mechanisms is vital to the development of appropriate therapeutics. We identified differentially expressed genes (DEGs) and differentially spliced genes (DSGs) across the clinical stages of AMD in disease-affected tissue, the macular retina pigment epithelium (RPE)/choroid and the macular neural retina within the same eye. We utilized 27 deeply phenotyped donor eyes (recovered within a 6 h postmortem interval time) from Caucasian donors (60-94 years) using a standardized published protocol. Significant findings were then validated in an independent set of well-characterized donor eyes (n = 85). There was limited overlap between DEGs and DSGs, suggesting distinct mechanisms at play in AMD pathophysiology. A greater number of previously reported AMD loci overlapped with DSGs compared to DEGs between disease states, and no DEG overlap with previously reported loci was found in the macular retina between disease states. Additionally, we explored allele-specific expression (ASE) in coding regions of previously reported AMD risk loci, uncovering a significant imbalance in C3 rs2230199 and CFH rs1061170 in the macular RPE/choroid for normal eyes and intermediate AMD (iAMD), and for CFH rs1061147 in the macular RPE/choroid for normal eyes and iAMD, and separately neovascular AMD (NEO). Only significant DEGs/DSGs from the macular RPE/choroid were found to overlap between disease states. STAT1, validated between the iAMD vs. normal comparison, and AGTPBP1, BBS5, CERKL, FGFBP2, KIFC3, RORα, and ZNF292, validated between the NEO vs. normal comparison, revealed an intricate regulatory network with transcription factors and miRNAs identifying potential upstream and downstream regulators. Findings regarding the complement genes C3 and CFH suggest that coding variants at these loci may influence AMD development via an imbalance of gene expression in a tissue-specific manner. Our study provides crucial insights into the multifaceted genomic underpinnings of AMD (i.e., tissue-specific gene expression changes, potential splice variation, and allelic imbalance), which may open new avenues for AMD diagnostics and therapies specific to iAMD and NEO.},
}
@article {pmid38066771,
year = {2023},
author = {Tan, TE and Tang, RWC and Chan, CM and Mathur, RS and Fenner, BJ},
title = {Diagnostic Challenges in ABCA4-Associated Retinal Degeneration: One Gene, Many Phenotypes.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {23},
pages = {},
pmid = {38066771},
issn = {2075-4418},
support = {SHF-SNEC 0920-4//The SingHealth Foundation/ ; },
abstract = {(1) Purpose: ABCA4-associated retinal degeneration (ABCA4-RD) is a phenotypically diverse disease that often evades diagnosis, even by experienced retinal specialists. This may lead to inappropriate management, delayed genetic testing, or inaccurate interpretation of genetic testing results. Here, we illustrate the phenotypic diversity of ABCA4-RD using a series of representative cases and compare these to other conditions that closely mimic ABCA4-RD. (2) Methods: Genetically confirmed ABCA4-RD cases with representative phenotypes were selected from an inherited retinal disease cohort in Singapore and compared to phenocopies involving other retinal diseases. (3) Results: ABCA4-RD phenotypes in this series included typical adolescent-onset Stargardt disease with flecks, bull's eye maculopathy without flecks, fundus flavimaculatus, late-onset Stargardt disease, and severe early-onset Stargardt disease. Phenocopies of ABCA4-RD in this series included macular dystrophy, pattern dystrophy, cone dystrophy, advanced retinitis pigmentosa, Leber congenital amaurosis, drug toxicity, and age-related macular degeneration. Key distinguishing features that often suggested a diagnosis of ABCA4-RD were the presence of peripapillary sparing, macular involvement and centrifugal distribution, and a recessive pedigree. (4) Conclusions: ABCA4-RD demonstrates a remarkable phenotypic spectrum that makes diagnosis challenging. Awareness of the clinical spectrum of disease can facilitate prompt recognition and accurate diagnostic testing.},
}
@article {pmid38066755,
year = {2023},
author = {Böhm, EW and Grauhan, NF and Pfeiffer, N and Gericke, A},
title = {Measurement of Retrobulbar Blood Flow and Vascular Reactivity-Relevance for Ocular and Cardiovascular Diseases.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {23},
pages = {},
pmid = {38066755},
issn = {2075-4418},
abstract = {Abnormal retrobulbar hemodynamics have been linked to the development of various ocular diseases, including glaucoma, age-related macular degeneration, and diabetic retinopathy. Additionally, altered retrobulbar blood flow has been observed in patients with severe cardiovascular diseases, including carotid artery occlusion, stroke, heart failure, and acute coronary syndrome. Due to the complex and intricate anatomy of retrobulbar blood vessels and their location behind the eyeball, measurement of retrobulbar blood flow and vascular reactivity, as well as the interpretation of the findings, are challenging. Various methods, such as color Doppler imaging, computed tomography angiography or magnetic resonance imaging, have been employed to assess retrobulbar blood flow velocities in vivo. Color Doppler imaging represents a fast and non-invasive method to measure retrobulbar blood flow velocities in vivo. While no information about vessel diameter can be gained performing this method, computed tomography angiography and magnetic resonance imaging provide information about vessel diameter and detailed information on the anatomical course. Additionally, ex vivo studies, such as myography, utilizing genetically modified animal models may provide high optical resolution for functional vascular investigations in these small vessels. To our best knowledge, this is the first review, presenting a detailed overview of methods aiming to evaluate retrobulbar blood flow and vascular reactivity in both humans and laboratory animals. Furthermore, we will summarize the disturbances observed in retrobulbar blood flow in retinal, optic nerve, and cardiovascular diseases.},
}
@article {pmid38064659,
year = {2024},
author = {Boscia, G and Ricardi, F and Gelormini, F and Marica, V and Conte, F and Ghilardi, A and Viggiano, P and Marolo, P and Bandello, F and Borrelli, E and Reibaldi, M},
title = {INTERSESSION REPEATABILITY OF READING PERFORMANCE MEASURES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {4},
pages = {707-713},
pmid = {38064659},
issn = {1539-2864},
mesh = {Humans ; *Vision Tests ; Reading ; Reproducibility of Results ; Visual Acuity ; *Macular Degeneration ; },
abstract = {PURPOSE: To assess the intersession repeatability of reading performance measures in patients with previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen).<br><br>METHODS: Ninety-one patients (91 eyes) with a diagnosis of previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (&#x2265;20/40 Snellen) were prospectively enrolled. Reading performance metrics were assessed using Radner charts, and these measurements were repeated after 7 days to obtain the intersession repeatability. To test repeatability, we calculated the intraclass correlation coefficient, the 95% coefficient of repeatability, and the coefficient of variation for each reading parameter: 1) reading acuity (RA-LogRAD); 2) maximal reading speed-words per minute; 3) RA score (RA score-LogRAD); and 4) critical print size-LogRAD.<br><br>RESULTS: Mean &#xb1; standard deviation best-corrected visual acuity was 0.13 &#xb1; 0.01 logMAR [range: 0.00-0.30 logMAR]. The intraclass correlation coefficient values indicated a good reliability for all the analyzed metrics (0.901 for RA; 0.859 for max reading speed; 0.906 for RA score; and 0.868 for critical print size). The coefficient of repeatability was 0.2 LogRAD for RA, 63.2 words per minute for max reading speed, 0.2 LogRAD for RA score, and 0.2 LogRAD for critical print size. Coefficient of variation was 5.5% for RA, 8.9% for max reading speed, 5.8% for RA score, and 6.9% for critical print size.<br><br>CONCLUSION: Reading performance metrics are characterized by good values of intersession repeatability in patients with neovascular age-related macular degeneration with good best-corrected visual acuity. Our findings may grant the employment of such measures in trials assessing the visual outcome in these patients.},
}
@article {pmid38064251,
year = {2023},
author = {Choi, K and Park, SJ and Han, S and Mun, Y and Lee, DY and Chang, DJ and Kim, S and Yoo, S and Woo, SJ and Park, KH and Suh, HS},
title = {Patient-Centered Economic Burden of Exudative Age-Related Macular Degeneration: Retrospective Cohort Study.},
journal = {JMIR public health and surveillance},
volume = {9},
number = {},
pages = {e49852},
pmid = {38064251},
issn = {2369-2960},
mesh = {Humans ; *Financial Stress ; *Macular Degeneration/epidemiology/diagnosis ; Patient-Centered Care ; Retrospective Studies ; Verteporfin ; Middle Aged ; },
abstract = {BACKGROUND: Exudative age-related macular degeneration (AMD), one of the leading causes of blindness, requires expensive drugs such as anti-vascular endothelial growth factor (VEGF) agents. The long-term regular use of effective but expensive drugs causes an economic burden for patients with exudative AMD. However, there are no studies on the long-term patient-centered economic burden of exudative AMD after reimbursement of anti-VEGFs.<br><br>OBJECTIVE: This study aimed to evaluate the patient-centered economic burden of exudative AMD for 2 years, including nonreimbursement and out-of-pocket costs, compared with nonexudative AMD using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM).<br><br>METHODS: This retrospective cohort study was conducted using the OMOP CDM, which included 2,006,478 patients who visited Seoul National University Bundang Hospital from June 2003 to July 2019. We defined the exudative AMD group as patients aged >50 years with a diagnosis of exudative AMD and a prescription for anti-VEGFs or verteporfin. The control group was defined as patients aged >50 years without a diagnosis of exudative AMD or a prescription for anti-VEGFs or verteporfin. To adjust for selection bias, controls were matched by propensity scores using regularized logistic regression with a Laplace prior. We measured any medical cost occurring in the hospital as the economic burden of exudative AMD during a 2-year follow-up period using 4 categories: total medical cost, reimbursement cost, nonreimbursement cost, and out-of-pocket cost. To estimate the average cost by adjusting the confounding variable and overcoming the positive skewness of costs, we used an exponential conditional model with a generalized linear model.<br><br>RESULTS: We identified 931 patients with exudative AMD and matched 783 (84.1%) with 2918 patients with nonexudative AMD. In the exponential conditional model, the total medical, reimbursement, nonreimbursement, and out-of-pocket incremental costs were estimated at US $3426, US $3130, US $366, and US $561, respectively, in the first year and US $1829, US $1461, US $373, and US $507, respectively, in the second year. All incremental costs in the exudative AMD group were 1.89 to 4.25 and 3.50 to 5.09 times higher in the first and second year, respectively, than those in the control group (P<.001 in all cases).<br><br>CONCLUSIONS: Exudative AMD had a significantly greater economic impact (P<.001) for 2 years on reimbursement, nonreimbursement, and out-of-pocket costs than nonexudative AMD after adjusting for baseline demographic and clinical characteristics using the OMOP CDM. Although economic policies could relieve the economic burden of patients with exudative AMD over time, the out-of-pocket cost of exudative AMD was still higher than that of nonexudative AMD for 2 years. Our findings support the need for expanding reimbursement strategies for patients with exudative AMD given the significant economic burden faced by patients with incurable and fatal diseases both in South Korea and worldwide.},
}
@article {pmid38063874,
year = {2024},
author = {Bilgic, A and Kodjikian, L and de Ribot, FM and Spitzer, MS and Vasavada, V and Gonzalez-Cortes, JH and Sudhalkar, A and Chakraborty, S and Mathis, T},
title = {Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {4},
pages = {1161-1167},
pmid = {38063874},
issn = {1435-702X},
mesh = {Humans ; Angiogenesis Inhibitors ; Antibodies, Monoclonal, Humanized/therapeutic use ; Intravitreal Injections ; *Macular Degeneration ; Receptors, Vascular Endothelial Growth Factor ; Retina ; Retrospective Studies ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {BACKGROUND: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting.<br><br>METHODS: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24&#xa0;months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24&#xa0;months of follow-up. Both treatment-na&#xef;ve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications.<br><br>RESULTS: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-na&#xef;ve group and switch therapy group, respectively. BCVA gain was&#x2009;+&#x2009;9.2 (3.7) letters (p&#x2009;=&#x2009;0.01) and&#x2009;+&#x2009;7.7 (3.4) letters (p&#x2009;=&#x2009;0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-na&#xef;ve group (from 432.5 (68.4) to 283.0 (51.3) &#xb5;m; p&#x2009;=&#x2009;0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) &#xb5;m; p&#x2009;=&#x2009;0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24.<br><br>CONCLUSION: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.},
}
@article {pmid38062839,
year = {2023},
author = {Zhang, R and Ji, Z and Quan, Z and Lu, Y and Ren, Y and He, Y},
title = {PEDF Prevents Mitochondrial Function Decay and ER Stress Induced by Rotenone in Aging RPE Cells.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {28},
number = {11},
pages = {319},
doi = {10.31083/j.fbl2811319},
pmid = {38062839},
issn = {2768-6698},
support = {82070964//National Natural Science Foundation of China/ ; 22KY0114//The fourth batch of school-level key disciplines of the Xi'an Medical University and Youth Project of the Second Affiliated Hospital of Xi 'an Medical University/ ; },
mesh = {Humans ; Aged ; Reactive Oxygen Species/metabolism ; *Rotenone/toxicity/metabolism ; *Calcium/metabolism ; Cells, Cultured ; Mitochondria/metabolism ; Adenosine Triphosphate/metabolism ; Oxidative Stress ; },
abstract = {BACKGROUND: Neurodegenerative diseases, including age-related macular degeneration (AMD), may be linked to mitochondrial dysfunction and endoplasmic reticulum (ER) stress. We examined whether Pigment epithelium-derived factor (PEDF) could prevent changes in the structure and function of these organelles by accelerating by rotenone (ROT), a mitochondrial inhibitor, in human retinal pigment epithelium (RPE) cells of chronological age.<br><br>METHODS: RPE cells from 9-20, 50-55, 60-70, and >70-year-old donors were isolated, grown as primary cultures, harvested, and treated with ROT and PEDF for electron microscope (EM), western blot analysis, and polymerase chain reaction (PCR). Reactive oxygen species (ROS) and cytoplasmic calcium [Ca2+]c and mitochondrial calcium [Ca2+]m levels were measured by flow cytometry using 2',7'-dichlorodihydrofluorescin diacetate (H2-DCF-DA), fluo-3/AM, and Rhod-2/AM, and ATP levels were measured using a luciferin/luciferase-based assay. Mitochondrial membrane potential (&#x394;&#x3a8;m) was detected using 5,5',6,6'-tetrachloro1,1',3,3'-tetraethylbenzimid azolocarbocyanine iodide (JC-1), and susceptibility of the cells to ROT toxicity and PEDF-protective effect was determined by propidium iodide (PI) staining and lactate dehydrogenase (LDH) assay. The expression of ER stress-related genes was detected using real-time (RT)-PCR.<br><br>RESULTS: We observed decay in the mitochondria of aged RPE cells, including matrix abnormalities, elongation, loss of cristae, and disruption of membrane integrity after ROT treatment. We also observed lower [Ca2+]c, higher ROS and [Ca2+]m levels, decreased &#x394;&#x3a8;m after ROT treatment, and greater susceptibility to ROT toxicity in aged RPE cells. PEDF can protect the cristae and integrity of the mitochondrial membrane, increase ATP levels and &#x394;&#x3a8;m, and lower ROS, [Ca2+]c, and [Ca2+]m in aged RPE cells induced by ROT. In addition, there was an increase in RDH expression in RPE cells with increasing age after PEDF treatment. Similarly, PEDF decreased the expression of ROT-induced ER stress-related genes.<br><br>CONCLUSIONS: Our study provides evidence that PEDF can reduce bioenergetic deficiencies, mitochondrial decay, and ER stress in aging RPE, a condition that may trigger the onset of retinal diseases such as AMD.},
}
@article {pmid38062823,
year = {2023},
author = {Liu, M and Wu, S and Wu, Y and Zhang, J and Chen, J and Peng, X and Yang, Q and Tan, Z and Zeng, Z},
title = {Rubus suavissimus S. Lee Extract Alleviates Oxidative Stress and Inflammation in H2O2-Treated Retinal Pigment Epithelial Cells and in High-Fat Diet-Fed Mouse Retinas.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {28},
number = {11},
pages = {279},
doi = {10.31083/j.fbl2811279},
pmid = {38062823},
issn = {2768-6698},
support = {KQ2203002//Changsha platform and talent plan/ ; KQ2202400//Changsha Natural Science Foundation/ ; 2021JJ30761//Natural Science Foundation of Hunan Province/ ; 2023JJ30090//Natural Science Foundation of Hunan Province/ ; 2022WK2008//Key R&amp;D Program of Hunan Province/ ; 2023SKX-KJ-08//International and Regional Science and Technology Exchange Project of Hunan Association for Science and Technology/ ; 22A0596//Scientific Research Fund of Hunan Provincial Education Department/ ; 22B0820//Scientific Research Fund of Hunan Provincial Education Department/ ; },
mesh = {Humans ; Mice ; Animals ; Aged ; Hydrogen Peroxide/metabolism ; *Rubus/metabolism ; Antioxidants/pharmacology/metabolism ; Diet, High-Fat/adverse effects ; Oxidative Stress ; Retina/pathology ; *Macular Degeneration/etiology/genetics ; Inflammation/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of visual disorders in the aged population and is characterized by the formation of retinal pigment epithelium (RPE) deposits and dysfunction/death of the RPE and photoreceptors. It is supposed that both oxidative stress and inflammation play a critical role in the pathogenesis of AMD. The development of therapeutic strategies against oxidative stress and inflammation in AMD is urgently needed. Rubus suavissimus S. Lee (RS), a medicinal plant growing in the southwest region of China, has been used as an herbal tea and medicine for various diseases.<br><br>METHODS: In this project, we evaluate the therapeutic potential of RS extract for AMD. We prepared RS extracts from dried leaves, which contained the main functional compounds.<br><br>RESULTS: RS extract significantly increased cell viability, upregulated the expression of antioxidant genes, lowered the generation of malondialdehyde and reactive oxygen species, and suppressed inflammation in H2O2-treated human RPE cells. In the in vivo study, treatment with RS extract attenuated body weight gain, lowered cholesterol and triglyceride levels in the liver and serum, increased antioxidant capacity, and alleviated inflammation in the retina and RPE/choroid of mice fed a high-fat diet.<br><br>CONCLUSIONS: Our findings suggest that RS extract offers therapeutic potential for treating AMD patients.},
}
@article {pmid38062449,
year = {2023},
author = {Jang, B and Lee, SY and Kim, C and Park, UC and Kim, YG and Lee, EK},
title = {Preliminary analysis of predicting the first recurrence in patients with neovascular age-related macular degeneration using deep learning.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {499},
pmid = {38062449},
issn = {1471-2415},
support = {23ZR1100//Electronics and Telecommunications Research Institute (ETRI) grant funded by the Korean government/ ; NRF-2021R1F1A1045417//National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (Information and Communication Technology)/ ; 0320222220//Seoul National University Hospital Research Fund/ ; },
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; *Deep Learning ; Retina/pathology ; Subretinal Fluid ; Tomography, Optical Coherence ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; Ranibizumab/therapeutic use ; },
abstract = {BACKGROUND: To predict, using deep learning, the first recurrence in patients with neovascular age-related macular degeneration (nAMD) after three monthly loading injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF).<br><br>METHODS: Optical coherence tomography (OCT) images were obtained at baseline and after the loading phase. The first recurrence was defined as the initial appearance of a new retinal hemorrhage or intra/subretinal fluid accumulation after the initial resolution of exudative changes after three loading injections. Standard U-Net architecture was used to identify the three retinal fluid compartments, which include pigment epithelial detachment, subretinal fluid, and intraretinal fluid. To predict the first recurrence of nAMD, classification learning was conducted to determine whether the first recurrence occurred within three months after the loading phase. The recurrence classification architecture was built using ResNet50. The model with retinal regions of interest of the entire region and fluid region on OCT at baseline and after the loading phase is presented.<br><br>RESULTS: A total of 1,444 eyes of 1,302 patients were included. The mean duration until the first recurrence after the loading phase was 8.20&#x2009;&#xb1;&#x2009;15.56 months. The recurrence classification system revealed that the model with the fluid region of OCT after the loading phase provided the highest classification performance, with an area under the receiver operating characteristic curve (AUC) of 0.725&#x2009;&#xb1;&#x2009;0.012. Heatmap analysis revealed that three pathological fluids, subsided choroidal neovascularization lesions, and hyperreflective foci were important areas for the first recurrence.<br><br>CONCLUSIONS: The deep learning algorithm allowed for the prediction of the first recurrence for three months after the loading phase with adequate feasibility. An automated prediction system may assist in establishing patient-specific treatment plans and the provision of individualized medical care for patients with nAMD.},
}
@article {pmid38061653,
year = {2024},
author = {Jia, H and Guo, Y and Luo, H and Meng, X and Zhang, L and Yu, K and Zheng, X and Sun, Y and Hu, W and Wu, Z and Chen, R and Sun, X},
title = {Association of long-term ozone air pollution and age-related macular degeneration in older Chinese population.},
journal = {The Science of the total environment},
volume = {912},
number = {},
pages = {169145},
doi = {10.1016/j.scitotenv.2023.169145},
pmid = {38061653},
issn = {1879-1026},
mesh = {Middle Aged ; Humans ; Aged ; *Ozone/analysis ; *Air Pollutants/analysis ; Cross-Sectional Studies ; Particulate Matter/analysis ; Environmental Exposure/analysis ; *Air Pollution ; China/epidemiology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of legal blindness. It remains unclear whether and to what extent the ambient ozone pollution could increase the risk of AMD.<br><br>METHODS: A nationwide cross-sectional survey was conducted in 129 major cities in 27 of 31 provincial regions across China from 2018 to 2021. Data in relation to demographics, residential address, and medical histories were collected. The exposure-response relationship between ozone exposure and AMD was explored using the restricted cubic splines. A piecewise logistic regression model was used to examine the magnitudes of the association, after adjusting demographic, social-economic and co-pollutants. Residential ozone exposures were estimated using a satellite-based model.<br><br>RESULTS: A total of 624,167 middle-aged and older participants were included in the final analyses, the overall prevalence of AMD was 16.76&#xa0;%. The risk of AMD was consistently increasing with higher warm-season ozone concentration, and the risk became much larger after the cut-off of 110&#xa0;&#x3bc;g/m[3] (approximately 50&#xa0;ppb). Every 10&#xa0;&#x3bc;g/m[3] increment in warm-season ozone concentration, the adjusted odds ratio (OR) for AMD were 1.15 (1.13, 1.16) and 1.66 (1.63, 1.69) when the warm-season ozone concentration was below or above 110&#xa0;&#x3bc;g/m[3], respectively.<br><br>CONCLUSION: This large-scale nationwide study provides the first epidemiological evidence demonstrating significant associations between long-term residential ozone exposure and AMD prevalence. Based on our findings, in conjunction with WHO global air quality guidelines, we suggest that a warm-season ozone of 110&#xa0;&#x3bc;g/m[3] should be adopted for middle-aged and older populations to reduce the risk of AMD. Ongoing efforts to reduce ozone exposure in communities through improved air quality regulations and public education are essential for the improvement of public health.},
}
@article {pmid38060000,
year = {2024},
author = {Feo, A and De Simone, L and Cimino, L and Angi, M and Romano, MR},
title = {Differential diagnosis of myopic choroidal neovascularization (mCNV): insights from multimodal imaging and treatment implications.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {7},
pages = {2005-2026},
pmid = {38060000},
issn = {1435-702X},
mesh = {Humans ; *Multimodal Imaging ; *Choroidal Neovascularization/diagnosis/drug therapy ; Diagnosis, Differential ; *Tomography, Optical Coherence/methods ; *Myopia, Degenerative/diagnosis/complications ; *Fluorescein Angiography/methods ; *Choroid/blood supply ; *Fundus Oculi ; },
abstract = {PURPOSE: The aim of this article is to conduct a comprehensive systematic review about the current understandings and differential diagnosis of myopic choroidal neovascularization (mCNV) and other several similar diseases, describing their multimodal imaging analysis, prognostic implications, and current types of management.<br><br>METHODS: This systematic review was performed based on a search on the PubMed database of relevant papers regarding mCNV and other entities discussed in the paper, according to our current knowledge.<br><br>RESULTS: Through the integration of a multimodal imaging approach, especially optical coherence tomography (OCT), along with accurate demographic and clinical assessment, it becomes possible to effectively differentiate mCNV from similar yet heterogeneous entities. These conditions include macular hemorrhage due to new lacquer crack (LC) formation, inflammatory diseases such as punctate inner choroidopathy (PIC)/multifocal choroidits (MFC) and epiphenomenon multiple evanescent white dot syndrome (Epi-MEWDS), neovascular age-related macular degeneration (nAMD), idiopathic CNV (ICNV), dome-shaped macula (DSM) with subretinal fluid, retinal pigment epithelium (RPE) humps, angioid streaks (AS), choroidal rupture (CR), and choroidal osteoma (CO). Each one of these entities will be described and discussed in this article.<br><br>CONCLUSION: Myopic choroidal neovascularization is a common retinal condition, especially among young individuals. Accurate diagnosis and differentiation from similar conditions are crucial for effective treatment. Multimodal imaging, particularly OCT, plays a crucial role in precise assessment. Future research should focus on defining biomarkers and distinguishing features to facilitate prompt treatment.},
}
@article {pmid38059999,
year = {2024},
author = {Feng, Q and Ruan, X and Lu, M and Bu, S and Zhang, Y},
title = {Metformin protects retinal pigment epithelium cells against H2O2-induced oxidative stress and inflammation via the Nrf2 signaling cascade.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {5},
pages = {1519-1530},
pmid = {38059999},
issn = {1435-702X},
support = {82171209//National Natural Science Foundation of China/ ; 202102010019//Guangzhou Science, Technology and Innovation Commission/ ; },
mesh = {Humans ; Reactive Oxygen Species/metabolism ; *Hydrogen Peroxide/toxicity/metabolism ; *NF-E2-Related Factor 2/genetics/metabolism ; Retinal Pigment Epithelium/metabolism ; Oxidative Stress ; Inflammation/drug therapy/prevention &amp; control/metabolism ; Cytokines/metabolism ; DNA ; Apoptosis ; },
abstract = {PURPOSE: Dysfunctions of retinal pigment epithelium (RPE) attributed to oxidative stress and inflammation are implicated with age-related macular degeneration (AMD). A debate on the curative role of metformin in AMD has been raised, though several recent clinical studies support the lower odds by using metformin. This study aimed to determine whether metformin could exert cytoprotection against RPE oxidative damages and the potential mechanisms.<br><br>METHODS: A cellular AMD model was established by treating ARPE-19 cells with hydrogen peroxide (H2O2) for 24&#xa0;h. The reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and levels of pro-inflammatory cytokines were monitored under administrations with H2O2 with/without metformin. The expression and DNA-binding activity of transcription factor erythroid-related factor 2 (Nrf2) were determined by western blot, immunofluorescence, and electrophoretic mobility shift assay. Knockout of Nrf2 was conducted by CRISPR/Cas9 gene deletion system.<br><br>RESULTS: Metformin pretreatment significantly improved the H2O2-induced low viability of ARPE-19 cells, reduced ROS production, and increased contents of antioxidative molecules. Concurrently, metformin also suppressed levels of pro-inflammatory cytokines caused by H2O2. The metformin-augmented nuclear translocation and DNA-binding activity of Nrf2 were further verified by the increased expression of its downstream targets. Genetic deletion of Nrf2 blocked the cytoprotective role of metformin.<br><br>CONCLUSION: Metformin possesses antioxidative and anti-inflammatory properties in ARPE-19 cells by activating the Nrf2 signaling. It supports the potential use for the control and prevention of AMD.},
}
@article {pmid38059165,
year = {2023},
author = {Song, F and Zhang, W and Zheng, Y and Shi, D and He, M},
title = {A deep learning model for generating fundus autofluorescence images from color fundus photography.},
journal = {Advances in ophthalmology practice and research},
volume = {3},
number = {4},
pages = {192-198},
pmid = {38059165},
issn = {2667-3762},
abstract = {BACKGROUND: Fundus Autofluorescence (FAF) is a valuable imaging technique used to assess metabolic alterations in the retinal pigment epithelium (RPE) associated with various age-related and disease-related changes. The practical uses of FAF are ever-growing. This study aimed to evaluate the effectiveness of a generative deep learning (DL) model in translating color fundus (CF) images into synthetic FAF images and explore its potential for enhancing screening of age-related macular degeneration (AMD).<br><br>METHODS: A generative adversarial network (GAN) model was trained on pairs of CF and FAF images to generate synthetic FAF images. The quality of synthesized FAF images was assessed objectively by common generation metrics. Additionally, the clinical effectiveness of the generated FAF images in AMD classification was evaluated by measuring the area under the curve (AUC), using the LabelMe dataset.<br><br>RESULTS: A total of 8410 FAF images from 2586 patients were analyzed. The synthesized FAF images exhibited an impressive objectively assessed quality, achieving a multi-scale structural similarity index (MS-SSIM) of 0.67. When evaluated on the LabelMe dataset, the combination of generated FAF images and CF images resulted in a noteworthy improvement in AMD classification accuracy, with the AUC increasing from 0.931 to 0.968.<br><br>CONCLUSIONS: This study presents the first attempt to use a generative deep learning model to create authentic and high-quality FAF images from CF images. The incorporation of the translated FAF images on top of CF images improved the accuracy of AMD classification. Overall, this study presents a promising approach to enhance large-scale AMD screening.},
}
@article {pmid38056552,
year = {2024},
author = {Bhutto, IA and McLeod, DS and Thomson, BR and Lutty, GA and Edwards, MM},
title = {Visualization of choroidal vasculature in pigmented mouse eyes from experimental models of AMD.},
journal = {Experimental eye research},
volume = {238},
number = {},
pages = {109741},
pmid = {38056552},
issn = {1096-0007},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY016151/EY/NEI NIH HHS/United States ; },
mesh = {Adult ; Humans ; Animals ; Mice ; *Hydrogen Peroxide ; Melanins ; Mice, Inbred C57BL ; Choroid/blood supply ; Retina/pathology ; *Choroidal Neovascularization/pathology ; },
abstract = {A variety of techniques exist to investigate retinal and choroidal vascular changes in experimental mouse models of human ocular diseases. While all have specific advantages, a method for evaluating the choroidal vasculature in pigmented mouse eyes has been more challenging especially for whole mount visualization and morphometric analysis. Here we report a simple, reliable technique involving bleaching pigment prior to immunostaining the vasculature in whole mounts of pigmented mouse choroids. Eyes from healthy adult pigmented C57BL/6J mice were used to establish the methodology. The retina and anterior segment were separated from the choroid. The choroid with retinal pigment epithelial cells (RPE) and sclera was soaked in 1% ethylenediaminetetraacetic acid (EDTA) to remove the RPE. Tissues were fixed in 2% paraformaldehyde (PFA) in phosphate-buffered saline (PBS). Choroids were subjected to melanin bleaching with 10% hydrogen peroxide (H2O2) at 55 °C for 90 min, washed in PBS and then immunostained with anti-podocalyxin antibody to label vascular endothelium followed by Cy3-AffiniPure donkey anti-goat IgG at 4 °C overnight. Images of immunostained bleached choroids were captured using a Zeiss 710 confocal microscope. In addition to control eyes, this method was used to analyze the choroids from subretinal sodium iodate (NaIO3) RPE atrophy and laser-induced choroidal neovascularization (CNV) mouse models. The H2O2 pretreatment effectively bleached the melanin, resulting in a transparent choroid. Immunolabeling with podocalyxin antibody following bleaching provided excellent visualization of choroidal vasculature in the flat perspective. In control choroids, the choriocapillaris (CC) displayed different anatomical patterns in peripapillary (PP), mid peripheral (MP) and far peripheral (FP) choroid. Morphometric analysis of the vascular area (VA) revealed that the CC was most dense in the PP region (87.4 ± 4.3% VA) and least dense in FP (79.9 ± 6.7% VA). CC diameters also varied depending on location from 11.4 ± 1.97 mm in PP to 15.1 ± 3.15 mm in FP. In the NaIO3-injected eyes, CC density was significantly reduced in the RPE atrophic regions (50.7 ± 5.8% VA in PP and 45.8 ± 6.17% VA in MP) compared to the far peripheral non-atrophic regions (82.8 ± 3.8% VA). CC diameters were significantly reduced in atrophic regions (6.35 ± 1.02 mm in PP and 6.5 ± 1.2 mm in MP) compared to non-atrophic regions (14.16 ± 2.12 mm). In the laser-induced CNV model, CNV area was 0.26 ± 0.09 mm[2] and luminal diameters of CNV vessels were 4.7 ± 0.9 mm. Immunostaining on bleached choroids with anti-podocalyxin antibody provides a simple and reliable tool for visualizing normal and pathologic choroidal vasculature in pigmented mouse eyes for quantitative morphometric analysis. This method will be beneficial for examining and evaluating the effects of various treatment modalities on the choroidal vasculature in mouse models of ocular diseases such as age-related macular degeneration, and degenerative genetic diseases.},
}
@article {pmid38055741,
year = {2023},
author = {Babapoor-Farrokhran, S and Qin, Y and Flores-Bellver, M and Niu, Y and Bhutto, IA and Aparicio-Domingo, S and Guo, C and Rodrigues, M and Domashevich, T and Deshpande, M and Megarity, H and Chopde, R and Eberhart, CG and Canto-Soler, V and Montaner, S and Sodhi, A},
title = {Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {50},
pages = {e2302845120},
pmid = {38055741},
issn = {1091-6490},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY025705/EY/NEI NIH HHS/United States ; R01 EY029750/EY/NEI NIH HHS/United States ; R01 EY035889/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; Humans ; Aged ; Retinal Pigment Epithelium/metabolism ; *Geographic Atrophy ; Hypoxia-Inducible Factor 1/metabolism ; Angiogenesis Inhibitors ; *Wet Macular Degeneration/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Visual Acuity ; *Choroidal Neovascularization/genetics/prevention &amp; control/metabolism ; Oxidants/metabolism ; Hypoxia/metabolism ; },
abstract = {It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.},
}
@article {pmid38055121,
year = {2024},
author = {Lowater, SJ and Grauslund, J and Subhi, Y and Vergmann, AS},
title = {Clinical Trials and Future Outlooks of the Port Delivery System with Ranibizumab: A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {1},
pages = {51-69},
pmid = {38055121},
issn = {2193-8245},
abstract = {The port delivery system (PDS) of anti-VEGF therapy provides continuous delivery of ranibizumab (RBZ). In October of 2021, the American Food and Drug Administration (FDA) approved the PDS with RBZ as a treatment option for neovascular age-related macular degeneration (nAMD). As the field of PDS with RBZ is progressing rapidly, this narrative review provides a much-needed overview of existing clinical trials as well as ongoing and upcoming trials investigating PDS with RBZ. The phase 2 LADDER trial reported that the mean time to first refill with RBZ PDS 100 mg/ml was 15.8 months (80% CI 12.1-20.6), and pharmacokinetic profiling revealed a sustained concentration of RBZ in serum and aqueous humor. Later, the phase 3 ARCHWAY trial reported that PDS with RBZ (100 mg/ml) refilled every 24 weeks was non-inferior to monthly intravitreal injection (IVI) with RBZ (0.5 mg) in patients with nAMD over 9 months and 2 years. However, patients with PDS had a higher rate of adverse events including vitreous hemorrhage and endophthalmitis. Patients indicate high treatment satisfaction with both PDS and IVI, but the lower number of treatments with PDS was reported as a preferred choice. Several ongoing and future clinical trials, of which details are discussed in this paper, are further exploring the potentials of PDS with RBZ. We conclude that the PDS provides continuous deliverance of RBZ and that clinical efficacy levels are non-inferior to IVI therapy for nAMD. Yet, a higher rate of adverse events remains a concerning detail for widespread implementation. Future studies are warranted to better understand which patients may benefit best from this treatment approach, if long-term efficacy can be sustained, and if safety of PDS can be further improved.},
}
@article {pmid38054895,
year = {2024},
author = {Rasmussen, KL and Frikke-Schmidt, R},
title = {The current state of apolipoprotein E in dyslipidemia.},
journal = {Current opinion in lipidology},
volume = {35},
number = {2},
pages = {78-84},
doi = {10.1097/MOL.0000000000000915},
pmid = {38054895},
issn = {1473-6535},
mesh = {Humans ; *Alzheimer Disease/genetics/epidemiology ; Genotype ; Apolipoproteins E/genetics ; Alleles ; *Vascular Diseases/genetics ; *Macular Degeneration/genetics ; *Dyslipidemias/genetics ; },
abstract = {PURPOSE OF REVIEW: Apolipoprotein E (apoE) plays a pivotal role in lipid metabolism in the peripheral circulation and in the brain. This has been recognized for decades; however, the importance of the full spectrum of variation in the APOE gene has been less investigated. This review focusses on current progresses in this field with main focus on apoE in dyslipidemia and vascular disease.<br><br>RECENT FINDINGS: Whereas &#x3b5;4 is the risk increasing allele for Alzheimer disease, &#x3b5;2 is associated with increased risk for age-related macular degeneration. Rare functional &#x3b5;2-like variants in APOE have previously been reported to have protective associations for Alzheimer disease but recent findings suggest a simultaneous high risk of age-related macular degeneration, in line with observations for the &#x3b5;2 allele.<br><br>SUMMARY: ApoE plays an important and well established role in dyslipidemia, vascular disease, and dementia. Recent evidence from large general population studies now also suggests that apoE is involved in age-related macular degeneration. ApoE-targeted therapeutics are being developed for multiple purposes; this heralds a promising change in the approach to disease processes involving apoE. The different risk profile for dementia and age-related macular degeneration should, however, be kept in mind when developing drugs targeting mechanisms resembling these variants.},
}
@article {pmid38052063,
year = {2024},
author = {Mehta, NJ and Mehta, SN},
title = {Nanotechnology in Retinal Disease: Current Concepts and Future Directions.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {40},
number = {1},
pages = {3-12},
pmid = {38052063},
issn = {1557-7732},
mesh = {Humans ; *Nanotechnology/methods ; *Retinal Diseases/diagnosis/drug therapy ; Drug Delivery Systems ; Liposomes/therapeutic use ; Blindness ; },
abstract = {The retina is one of the most complex and extraordinary human organs affected by genetic, metabolic, and degenerative diseases, resulting in blindness for ∼1.3 million people in the United States and over 40 million people worldwide. This translates into a huge loss of productivity, especially among younger patients with inherited retinal diseases (IRDs) and diabetic retinopathy. Age-related macular degeneration accounts for 90% of all blindness cases worldwide. The prevalence of this condition is projected to reach over 5 million individuals over the next 3 decades. There are also >20 IRD phenotypes, affecting >2 million people worldwide. Nanobiotechnology uses nanotechnology for biological applications, making use of biological materials either conceptually or directly in the fabrication of new materials. Bionanotechnology, on the other hand, uses molecular biology for the purpose of creating nanostructures (ie, structures with at least 1 dimension <100 nm). Retinal applications of these technologies are developing at a rapid pace. This review includes the most current nanotechnological applications in retinal diagnostics, theranostics, drug delivery, and targeting, including the potential for nonviral vehicles such as liposomes, micelles, and dendrimers, which pose advantages over viral vectors in retinal drug delivery. Furthermore, we discuss current and future applications as surgical adjuncts and in regenerative medicine as they pertain to retinal disease. Structure and function of nanoparticles such as carbon nanotubules, quantum dots, and magnetic nanoparticles, as well as diagnostic technologies such as next-generation DNA sequencing and single-molecule bionanosensing, will also be discussed.},
}
@article {pmid38047930,
year = {2024},
author = {Grimaldi, G and Cancian, G and Rizzato, A and Casanova, A and Perruchoud-Ader, K and Clerici, M and Consigli, A and Menghini, M},
title = {Intravitreal faricimab for neovascular age-related macular degeneration previously treated with traditional anti-VEGF compounds: a real-world prospective study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {4},
pages = {1151-1159},
pmid = {38047930},
issn = {1435-702X},
support = {50000 CHF//Bayer Switzerland AG/ ; },
mesh = {Humans ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors ; Prospective Studies ; Intravitreal Injections ; Visual Acuity ; Ranibizumab ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factors ; *Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/therapeutic use ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Antibodies, Bispecific ; },
abstract = {BACKGROUND/AIMS: To evaluate the efficacy, safety and durability of intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) with unsatisfactory response to traditional anti-vascular endothelial growth factor (anti-VEGF) agents.<br><br>METHODS: Single-centre, prospective cohort study of all consecutive patients with nAMD who were switched to intravitreal faricimab from intravitreal ranibizumab or aflibercept, due to unsatisfactory treatment response (maximal fluid-free interval&#x2009;&#x2264;&#x2009;8&#xa0;weeks). Intravitreal faricimab was administered with a loading dose of four 4-weekly injections, followed by an 8-week extension. A treat and extend (T&amp;E) regime was adopted thereafter. Primary outcome was the difference between the maximal fluid-free interval achieved with faricimab, and the one achieved before the switch. Morpho-functional outcomes were also assessed. Secondary outcome was accordance with clinical management when applying faricimab pivotal trial criteria versus our real-world T&amp;E protocol, measured as a proportion.<br><br>RESULTS: Twenty-six eyes of 26 patients with a median age of 82&#xa0;years (range 77-85) were included. Patients were followed for 30.2&#xa0;weeks (range 26.3-33.1). Maximal fluid-free interval after switch to faricimab (Mdn&#x2009;=&#x2009;6.0&#xa0;weeks; IQR&#x2009;=&#x2009;4-8) was longer than the maximum interval before the switch (Mdn&#x2009;=&#x2009;4.0&#xa0;weeks; IQR&#x2009;=&#x2009;4-4), p&#x2009;<&#x2009;0.001. Comparing real-world T&amp;E protocol with pivotal trial criteria, 8 (30.8%) eyes received the same clinical management while 18 (69.2%) eyes were kept at a shorter interval when following our T&amp;E protocol. No serious adverse events were recorded.<br><br>CONCLUSIONS: Faricimab appears to increase the fluid-free interval and allow extension of dosing interval in patients with nAMD poorly responsive to traditional anti-VEGF drugs.},
}
@article {pmid38046618,
year = {2023},
author = {Saidi, L and Jomaa, H and Zainab, H and Zgolli, H and Mabrouk, S and Sidibé, D and Tabia, H and Khlifa, N},
title = {Automatic Detection of AMD and DME Retinal Pathologies Using Deep Learning.},
journal = {International journal of biomedical imaging},
volume = {2023},
number = {},
pages = {9966107},
pmid = {38046618},
issn = {1687-4188},
abstract = {Diabetic macular edema (DME) and age-related macular degeneration (AMD) are two common eye diseases. They are often undiagnosed or diagnosed late. This can result in permanent and irreversible vision loss. Therefore, early detection and treatment of these diseases can prevent vision loss, save money, and provide a better quality of life for individuals. Optical coherence tomography (OCT) imaging is widely applied to identify eye diseases, including DME and AMD. In this work, we developed automatic deep learning-based methods to detect these pathologies using SD-OCT scans. The convolutional neural network (CNN) from scratch we developed gave the best classification score with an accuracy higher than 99% on Duke dataset of OCT images.},
}
@article {pmid38045700,
year = {2023},
author = {Krishnan, A and Sendra, VG and Patel, D and Lad, A and Greene, MK and Smyth, P and Gallaher, SA and Herron, &#xda;M and Scott, CJ and Genead, M and Tolentino, M},
title = {PolySialic acid-nanoparticles inhibit macrophage mediated inflammation through Siglec agonism: a potential treatment for age related macular degeneration.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1237016},
pmid = {38045700},
issn = {1664-3224},
mesh = {Mice ; Humans ; Animals ; Sialic Acid Binding Immunoglobulin-like Lectins ; *Macular Degeneration/drug therapy ; Macrophages ; *Retinal Degeneration ; Inflammation/drug therapy ; *Nanoparticles ; },
abstract = {Age-related macular degeneration (AMD) is a chronic, progressive retinal disease characterized by an inflammatory response mediated by activated macrophages and microglia infiltrating the inner layer of the retina. In this study, we demonstrate that inhibition of macrophages through Siglec binding in the AMD eye can generate therapeutically useful effects. We show that Siglecs-7, -9 and -11 are upregulated in AMD associated M0 and M1 macrophages, and that these can be selectively targeted using polysialic acid (PolySia)-nanoparticles (NPs) to control dampen AMD-associated inflammation. In vitro studies showed that PolySia-NPs bind to macrophages through human Siglecs-7, -9, -11 as well as murine ortholog Siglec-E. Following treatment with PolySia-NPs, we observed that the PolySia-NPs bound and agonized the macrophage Siglecs resulting in a significant decrease in the secretion of IL-6, IL-1β, TNF-α and VEGF, and an increased secretion of IL-10. In vivo intravitreal (IVT) injection of PolySia-NPs was found to be well-tolerated and safe making it effective in preventing thinning of the retinal outer nuclear layer (ONL), inhibiting macrophage infiltration, and restoring electrophysiological retinal function in a model of bright light-induced retinal degeneration. In a clinically validated, laser-induced choroidal neovascularization (CNV) model of exudative AMD, PolySia-NPs reduced the size of neovascular lesions with associated reduction in macrophages. The PolySia-NPs described herein are therefore a promising therapeutic strategy for repolarizing pro-inflammatory macrophages to a more anti-inflammatory, non-angiogenic phenotype, which play a key role in the pathophysiology of non-exudative AMD.},
}
@article {pmid38044597,
year = {2023},
author = {Szewczuk, A and Zaleska-Żmijewska, A and Dziedziak, J and Szaflik, JP},
title = {Clinical Application of Adaptive Optics Imaging in Diagnosis, Management, and Monitoring of Ophthalmological Diseases: A Narrative Review.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {29},
number = {},
pages = {e941926},
pmid = {38044597},
issn = {1643-3750},
mesh = {Humans ; Retina/diagnostic imaging/pathology ; Ophthalmoscopy/methods ; Tomography, Optical Coherence/methods ; *Diabetic Retinopathy/pathology ; *Central Serous Chorioretinopathy ; },
abstract = {Visualization of the retinal structure is crucial for understanding the pathophysiology of ophthalmic diseases, as well as for monitoring their course and treatment effects. Until recently, evaluation of the retina at the cellular level was only possible using histological methods, because the available retinal imaging technology had insufficient resolution due to aberrations caused by the optics of the eye. Adaptive optics (AO) technology improved the resolution of optical systems to 2 µm by correcting optical wave-front aberrations, thereby revolutionizing methods for studying eye structures in vivo. Within 25 years of its first application in ophthalmology, AO has been integrated into almost all existing retinal imaging devices, such as the fundus camera (FC), scanning laser ophthalmoscopy (SLO), and optical coherence tomography (OCT). Numerous studies have evaluated individual retinal structures, such as photoreceptors, blood vessels, nerve fibers, ganglion cells, lamina cribrosa, and trabeculum. AO technology has been applied in imaging structures in healthy eyes and in various ocular diseases. This article aims to review the roles of AO imaging in the diagnosis, management, and monitoring of age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, hypertensive retinopathy (HR), central serous chorioretinopathy (CSCR), and inherited retinal diseases (IRDs).},
}
@article {pmid38044420,
year = {2023},
author = {Hoshi, K and Kunikata, H and Aizawa, N and Yasuda, M and Okabe, T and Takizawa, H and Abe, T and Nakazawa, T},
title = {Baseline characteristics associated with the incidence of intraocular inflammation after the intravitreous injection of brolucizumab.},
journal = {International ophthalmology},
volume = {43},
number = {12},
pages = {4701-4709},
pmid = {38044420},
issn = {1573-2630},
support = {Scientific Research (C) (H.K. 17K11445)//JST grants from JSPS KAKENHI Grants-in-Aid/ ; COI-NEXT (JPMJPF2201).//JST grants/ ; },
mesh = {Humans ; Incidence ; Retrospective Studies ; *Uveitis ; Inflammation ; Intravitreal Injections ; *Macula Lutea ; Angiogenesis Inhibitors/adverse effects ; *Wet Macular Degeneration ; },
abstract = {PURPOSE: To investigate baseline characteristics associated with the incidence of intraocular inflammation (IOI) after the intravitreal injection of brolucizumab (IVBr) for the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective study included 66 eyes of 62 consecutive patients with nAMD who received IVBr (18 eyes were treatment na&#xef;ve and 48 eyes had switched from other anti-vascular endothelial growth factor [VEGF] therapy). Baseline clinical characteristics were compared in non-IOI and IOI groups.<br><br>RESULTS: Although a dry macula was achieved at a high rate even 6 months after IVBr, IOI occurred in 8 of 66 eyes (12.1%; all had switched therapy) during the study period. Baseline characteristics including age, sex, nAMD type, lens status, visual acuity, central macular thickness, and a history of diabetes did not differ between the groups. The number of previous anti-VEGF injections before IVBr was greater in the IOI group (P&#x2009;=&#x2009;0.004), and the ratio of patients with a laser flare-cell photometry (LFCP) value over 15 photon count per millisecond (pc/ms) was higher in the IOI group (P&#x2009;=&#x2009;0.017). Multivariate logistic regression analysis showed that a greater number of previous anti-VEGF injections (odds ratio [OR]: 1.12,&#xa0;P&#x2009;=&#x2009;0.006; area under the curve: 0.82, cut-off score: 14.0) and an LFCP value over 15 pc/ms (OR: 81.6,&#xa0;P&#x2009;=&#x2009;0.031) were significantly associated with the incidence of IOI after IVBr.<br><br>CONCLUSION: A number of previous anti-VEGF injections greater than 14 and an LFCP value more than 15 pc/ms might be useful predictors of the incidence of IOI after IVBr in eyes with nAMD.},
}
@article {pmid38041224,
year = {2023},
author = {Gettman, L},
title = {New Drugs: Faricimab-svoa (Vabysmo[™]) for Macular Degeneration and Diabetic Macular Edema and Omidenepag Isopropyl (Omlonti[™]) for Glaucoma and Ocular Hypertension.},
journal = {The Senior care pharmacist},
volume = {38},
number = {12},
pages = {497-500},
doi = {10.4140/TCP.n.2023.497},
pmid = {38041224},
issn = {2639-9636},
mesh = {Humans ; *Macular Edema/drug therapy ; *Diabetic Retinopathy/drug therapy ; *Glaucoma/drug therapy ; *Ocular Hypertension/drug therapy ; *Macular Degeneration ; *Diabetes Mellitus ; },
abstract = {Two drugs are covered in this quarterly column. Faricimab-svoa (Vabysmo[™]) for Macular Degeneration and Diabetic Macular Edema and Omidenepag Isopropyl (Omlonti[™]) for Glaucoma and Ocular Hypertension.},
}
@article {pmid38040965,
year = {2024},
author = {Pereira, DS and Akita, K and Bhisitkul, RB and Nishihata, T and Ali, Y and Nakamura, E and Nakamura, Y},
title = {Safety and tolerability of intravitreal umedaptanib pegol (anti-FGF2) for neovascular age-related macular degeneration (nAMD): a phase 1, open-label study.},
journal = {Eye (London, England)},
volume = {38},
number = {6},
pages = {1149-1154},
pmid = {38040965},
issn = {1476-5454},
mesh = {Humans ; Angiogenesis Inhibitors/adverse effects ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Retina/drug effects/pathology ; Treatment Outcome ; Wet Macular Degeneration/drug therapy ; },
abstract = {OBJECTIVE: To evaluate the efficacy and safety of a single-dose intravitreal umedaptanib pegol (anti-FGF2, investigational new drug) for the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Nine participants who had a diagnosis of refractory nAMD were enrolled and received a single intravitreal injection of umedaptanib pegol at increasing doses of 0.2, 1.0 or 2.0&#x2009;mg in the study eye.<br><br>RESULTS: All three doses of umedaptanib pegol evaluated in the study were safe and well tolerated. No severe adverse event (AE) was observed in the study. There was an improvement in retinal fluid measured by central subfield thickness (CST) in most subjects. Remarkably, all three subjects who received 2.0&#x2009;mg/eye showed improvement of more than 150&#x2009;&#x3bc;m.<br><br>CONCLUSIONS: Intravitreal umedaptanib pegol was safe, well tolerated, and demonstrated an indication of bioactivity in participants that have persistent subretinal fluid refractory to the treatment with anti-VEGFs.},
}
@article {pmid38040962,
year = {2024},
author = {Choi, M and Han, S and Kim, SW and Yun, C and Oh, J},
title = {Volume-rendering three-dimensional image analysis of macular neovascularization in age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {6},
pages = {1125-1132},
pmid = {38040962},
issn = {1476-5454},
support = {NRF- 2020R1A2C1005729//Ministry of Science, ICT and Future Planning (MSIP)/ ; },
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Imaging, Three-Dimensional ; Retrospective Studies ; *Macular Degeneration/drug therapy ; *Choroidal Neovascularization/diagnostic imaging/drug therapy ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; Fluorescein Angiography ; },
abstract = {BACKGROUND: To visualize and investigate the three-dimensional (3D) images of macular neovascularization (MNV) in eyes with neovascular age-related macular degeneration using optical coherence tomography angiography (OCTA) according to the treatment response to intravitreal aflibercept injection (IVI).<br><br>METHODS: OCTA images at baseline and 12 weeks (after three loading IVIs) were retrospectively reconstructed as 3D images for patients with type 1 and 2 MNV treated with the "pro-re-nata" regimen. The fluid-free and persistent fluid groups were divided according to the presence of subretinal and intraretinal fluid at 12 weeks after treatment. Using reconstructed 3D images of MNV, the volume, average volume per slice, and z-axis of the volumetric structure were evaluated.<br><br>RESULTS: Twenty-three and nine were classified into the fluid-free and persistent fluid groups, respectively. The MNV volume decreased significantly from baseline to 12 weeks in the fluid-free group (p&#x2009;=&#x2009;0.005), not in the persistent fluid group (p&#x2009;=&#x2009;0.250). The average volume of MNV per slice at 12 weeks correlated with the persistent fluid group in both the univariate and multivariate analyses (p&#x2009;=&#x2009;0.034, p&#x2009;=&#x2009;0.039, Exp [B] = 14.005).<br><br>CONCLUSIONS: This study may provide a perspective on vascular volumetric changes of MNV according to treatment response.},
}
@article {pmid38040055,
year = {2024},
author = {Raimondi, R and Felfel, T and Bogdanova-Bennet, A and Varma, D and Habib, M and Kotagiri, A and Steel, DH and Grinton, M},
title = {Outcomes of Treatment-Resistant Neovascular Age-Related Macular Degeneration Switched from Aflibercept to Faricimab.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {6},
pages = {537-544},
doi = {10.1016/j.oret.2023.11.015},
pmid = {38040055},
issn = {2468-6530},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/antagonists &amp; inhibitors ; *Recombinant Fusion Proteins/administration &amp; dosage ; Retrospective Studies ; Male ; Female ; *Intravitreal Injections ; *Visual Acuity ; *Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Drug Substitution/methods ; Treatment Outcome ; Follow-Up Studies ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Fluorescein Angiography/methods ; Fundus Oculi ; Macula Lutea/pathology/diagnostic imaging ; },
abstract = {PURPOSE: Although previous studies have demonstrated the efficacy of faricimab in treatment-naive patients with neovascular age-related macular degeneration (nAMD), its outcomes in patients switched from aflibercept are less understood. This study aimed to assess clinical anatomical and functional outcomes of switching to faricimab in patients undergoing aflibercept intravitreal injections (IVIs) for nAMD with suboptimal response.<br><br>DESIGN: Retrospective case series.<br><br>SUBJECTS: Patients with nAMD at a single tertiary care center who were switched from aflibercept to faricimab due to persistent suboptimal response.<br><br>METHODS: Patients had received a minimum of 6 consecutive IVIs of aflibercept and showed persistent presence of intraretinal (IRF) or subretinal fluid (SRF) on OCT despite receiving aflibercept at 4 or 6-weekly intervals at the time of the switch. Patients receiving 4-weekly aflibercept were switched with either 2 or 3 loading doses of 4-weekly faricimab injections. Regression models were used to identify predictors of clinical outcomes.<br><br>MAIN OUTCOME MEASURES: Visual acuity, central macular thickness (CMT), and OCT parameters were assessed preswitch and postswitch.<br><br>RESULTS: Eighty-one eyes of 68 patients were included. The mean age was 79.1 years (standard deviation: 8.9), and females constituted 53% of cases. A statistically significant reduction in CMT was observed postswitch (P < 0.0001). The proportion of cases with IRF (P&#xa0;= 0.0219) and SRF (P < 0.000) decreased significantly. Overall clinical improvement on OCT was noted in 80% of patients. No significant improvement in ETDRS vision was observed. There was no evidence that switching regimen (2 vs. 3 loading doses) had an independent effect on clinical outcomes.<br><br>CONCLUSION: Among patients with treatment-resistant nAMD, switching from aflibercept to faricimab may serve as a safe and effective option. Significant anatomical improvements were observed, with a trend toward visual stability. The loading regimen with 2 faricimab injections appeared to be sufficient for nonnaive patients. However, a longer follow-up and larger studies are warranted to confirm these findings.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38036892,
year = {2024},
author = {Ghzaiel, I and Maaloul, S and Ksila, M and Namsi, A and Yammine, A and Debbabi, M and Badreddine, A and Meddeb, W and Pires, V and Nury, T and Ménétrier, F and Avoscan, L and Zarrouk, A and Baarine, M and Masmoudi-Kouki, O and Ghrairi, T and Abdellaoui, R and Nasser, B and Hammami, S and Hammami, M and Samadi, M and Vejux, A and Lizard, G},
title = {In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy.},
journal = {Advances in experimental medicine and biology},
volume = {1440},
number = {},
pages = {437-452},
pmid = {38036892},
issn = {0065-2598},
mesh = {Humans ; Animals ; Mice ; *Apoptosis ; *Mitochondria/metabolism ; Ketocholesterols/metabolism ; },
abstract = {7-Ketocholesterol and 7β-hydroxycholesterol are most often derived from the autoxidation of cholesterol. Their quantities are often increased in the body fluids and/or diseased organs of patients with age-related diseases such as cardiovascular diseases, Alzheimer's disease, age-related macular degeneration, and sarcopenia which are frequently associated with a rupture of RedOx homeostasis leading to a high oxidative stress contributing to cell and tissue damages. On murine cells from the central nervous system (158N oligodendrocytes, microglial BV-2 cells, and neuronal N2a cells) as well as on C2C12 murine myoblasts, these two oxysterols can induce a mode of cell death which is associated with qualitative, quantitative, and functional modifications of the peroxisome. These changes can be revealed by fluorescence microscopy (apotome, confocal microscopy), transmission electron microscopy, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and gas chromatography-coupled with mass spectrometry (GC-MS). Noteworthy, several natural molecules, including ω3 fatty acids, polyphenols, and α-tocopherol, as well as several Mediterranean oils [argan and olive oils, Milk-thistle (Sylibum marianum) and Pistacia lenticus seed oils], have cytoprotective properties and attenuate 7-ketocholesterol- and 7β-hydroxycholesterol-induced peroxisomal modifications. These observations led to the concept of pexotherapy.},
}
@article {pmid38036885,
year = {2024},
author = {Olivier, E and Rat, P},
title = {Role of Oxysterols in Ocular Degeneration Mechanisms and Involvement of P2X7 Receptor.},
journal = {Advances in experimental medicine and biology},
volume = {1440},
number = {},
pages = {277-292},
pmid = {38036885},
issn = {0065-2598},
mesh = {Humans ; Receptors, Purinergic P2X7 ; *Oxysterols ; Quality of Life ; Eye/pathology ; *Macular Degeneration/metabolism ; *Diabetic Retinopathy/complications ; },
abstract = {Ocular degeneration, including cataracts, glaucoma, macular degeneration, and diabetic retinopathy, is a major public health challenge, as it affects the quality of life of millions of people worldwide and, in its advanced stages, leads to blindness. Ocular degeneration, although it can affect different parts of the eye, shares common characteristics such as oxysterols and the P2X7 receptor. Indeed, oxysterols, which are cholesterol derivatives, are associated with ocular degeneration pathogenesis and trigger inflammation and cell death pathways. Activation of the P2X7 receptor is also linked to ocular degeneration and triggers the same pathways. In age-related macular degeneration, these two key players have been associated, but further studies are needed to extrapolate this interrelationship to other ocular degenerations.},
}
@article {pmid38036880,
year = {2024},
author = {Ghosh, S and Ghzaiel, I and Vejux, A and Meaney, S and Nag, S and Lizard, G and Tripathi, G and Naez, F and Paul, S},
title = {Impact of Oxysterols in Age-Related Disorders and Strategies to Alleviate Adverse Effects.},
journal = {Advances in experimental medicine and biology},
volume = {1440},
number = {},
pages = {163-191},
pmid = {38036880},
issn = {0065-2598},
mesh = {Animals ; Cholesterol ; *Drug-Related Side Effects and Adverse Reactions ; *Neurodegenerative Diseases ; Oxidation-Reduction ; *Oxysterols ; Sterols ; },
abstract = {Oxysterols or cholesterol oxidation products are a class of molecules with the sterol moiety, derived from oxidative reaction of cholesterol through enzymatic and non-enzymatic processes. They are widely reported in animal-origin foods and prove significant involvement in the regulation of cholesterol homeostasis, lipid transport, cellular signaling, and other physiological processes. Reports of oxysterol-mediated cytotoxicity are in abundance and thus consequently implicated in several age-related and lifestyle disorders such as cardiovascular diseases, bone disorders, pancreatic disorders, age-related macular degeneration, cataract, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, and some types of cancers. In this chapter, we attempt to review a selection of physiologically relevant oxysterols, with a focus on their formation, properties, and roles in health and disease, while also delving into the potential of natural and synthetic molecules along with bacterial enzymes for mitigating oxysterol-mediated cell damage.},
}
@article {pmid38036627,
year = {2023},
author = {Tamiya, R and Hata, M and Tanaka, A and Tsuchikawa, M and Ueda-Arakawa, N and Tamura, H and Miyata, M and Takahashi, A and Kido, A and Muraoka, Y and Miyake, M and Ooto, S and Tsujikawa, A},
title = {Therapeutic effects of faricimab on aflibercept-refractory age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {21128},
pmid = {38036627},
issn = {2045-2322},
support = {21H03092//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Ranibizumab ; Vascular Endothelial Growth Factor A ; Treatment Outcome ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy ; },
abstract = {Though vascular endothelial growth factors (VEGF) and other proangiogenic factors, such as angiopoietins (Ang), may be involved in the development of neovascular age-related macular degeneration (nvAMD), only drugs that inhibit the VEGF family are available for the treatment. The newly approved anti-VEGF drug faricimab, which also inhibits Ang-2, is expected to be effective in patients with AMD refractory to conventional anti-VEGF drugs. Therefore, we prospectively investigated the efficacy of faricimab in the treatment of aflibercept-refractory nvAMD. Patients with nvAMD who had been treated with aflibercept in the last year and required bimonthly injections were recruited. 25 eyes showed persistent exudative changes immediately before the faricimab injection (baseline). In these 25 eyes, switching to faricimab did not change visual acuity or central retinal thickness 2 months after the injection; however, 56% of eyes showed reduction or complete absorption of fluid. Notably, 25% of the eyes that showed dry macula at month 2 had no fluid recurrence for up to 4 months. These results indicate that faricimab could benefit some patients with aflibercept-refractory nvAMD.},
}
@article {pmid38036609,
year = {2024},
author = {Pereira, DS and Maturi, RK and Akita, K and Mahesh, V and Bhisitkul, RB and Nishihata, T and Sakota, E and Ali, Y and Nakamura, E and Bezwada, P and Nakamura, Y},
title = {Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients.},
journal = {Eye (London, England)},
volume = {38},
number = {6},
pages = {1140-1148},
pmid = {38036609},
issn = {1476-5454},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Disease Progression ; *Fibroblast Growth Factor 2/antagonists &amp; inhibitors ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Ranibizumab/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factor A/therapeutic use ; },
abstract = {BACKGROUND/OBJECTIVE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative age-related macular degeneration (nAMD). Due to the limitations of these standard therapies, targeting alternative mechanisms of action may be helpful for treatment of this very common disease. Here, we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, umedaptanib pegol, a next generation therapeutic for the treatment of nAMD.<br><br>METHODS: Three phase 2 studies were designed. First, a multicentre, randomized, double-masked TOFU study assessed the efficacy of intravitreal injections of umedaptanib pegol monotherapy or in combination with aflibercept, compared to aflibercept monotherapy in 86 subjects with anti-VEGF pretreated nAMD. Second, 22 subjects who had exited the TOFU study received 4 monthly intravitreal injections of umedaptanib pegol (extension, RAMEN study). Third, as an investigator-sponsored trial (TEMPURA study), a single-center, open-label, 4-month study was designed to evaluate the safety and treatment efficacy of umedaptanib pegol in five na&#xef;ve nAMD patients who had not received any prior anti-VEGF treatment.<br><br>RESULTS: The TOFU study demonstrated that umedaptanib pegol alone or in combination with aflibercept did not improve best-corrected visual acuity (BCVA) and central subfield thickness (CST) over aflibercept alone. However, the change in BCVA and CST at primary endpoint was marginal in all the three treatment groups, suggesting that umedaptanib pegol is effective to prevent the disease progression. The RAMEN study confirmed the cessation of disease progression. In the TEMPURA study, na&#xef;ve nAMD patients showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients.<br><br>CONCLUSIONS: These results demonstrate, for the first time, clinical proof of concept for aptamer based anti-FGF2 therapy of nAMD.},
}
@article {pmid38036571,
year = {2023},
author = {Neiteler, A and Palakkan, AA and Gallagher, KM and Ross, JA},
title = {Oxidative stress and docosahexaenoic acid injury lead to increased necroptosis and ferroptosis in retinal pigment epithelium.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {21143},
pmid = {38036571},
issn = {2045-2322},
support = {MR/N002210/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Retinal Pigment Epithelium/metabolism ; Docosahexaenoic Acids/pharmacology/metabolism ; *Ferroptosis ; Hydrogen Peroxide/metabolism ; Necroptosis ; Oxidative Stress ; *Macular Degeneration/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a complex disease caused by different genetic and environmental risk factors leading to loss of cells in the central part of the retina. Oxidative stress appears to be an important environmental risk factor that contributes to both the initiation and progression of AMD. Retinal pigment epithelium (RPE) plays an important role in regulating oxidative stress in the retina and is one of the main retinal cell types affected in AMD. A main function of RPE is to phagocytose photoreceptor outer segments (POS) which are rich in the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA), making this cell type potentially more susceptible to oxidative stress-induced lipid peroxidation which can lead to cell death. RPE is known to undergo necrotic cell death in response to oxidative stress. The aim of this study was to determine if DHA in POS can increase oxidative damage to RPE. It was found that RPE undergo increased lipid peroxidation and decreased cell viability when stressed with hydrogen peroxide in combination with DHA or POS. H2O2-induced oxidative stress was found to cause both ferroptosis and necroptosis. However, the ferroptosis regulator acyl-CoA synthetase long-chain family member 4 (ACSL4) was found to be downregulated in RPE exposed to H2O2 and this effect was exacerbated when the RPE cells were simultaneously treated with DHA. Together, these results show a response of RPE when stressed which will likely be overwhelmed under disease conditions such as AMD resulting in cell death.},
}
@article {pmid38032336,
year = {2023},
author = {Larsen, PP and Féart, C and Pais de Barros, JP and Merle, BMJ and Gayraud, L and Delyfer, MN and Korobelnik, JF and Delcourt, C},
title = {Association of Age-Related Macular Degeneration with a Blood Biomarker of Lipopolysaccharide, a Gut Bacterial Proinflammatory Toxin.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {14},
pages = {47},
pmid = {38032336},
issn = {1552-5783},
mesh = {Humans ; Lipopolysaccharides ; *Gastrointestinal Microbiome ; Prospective Studies ; *Macular Degeneration/diagnosis ; *Bacterial Toxins ; Biomarkers ; },
abstract = {PURPOSE: Chronic inflammation, immune dysregulation, and oxidative stress are major drivers of age-related macular degeneration (AMD) pathogenesis. Lipopolysaccharide (LPS) is a potent proinflammatory toxin originating from gut bacteria. We assessed the association of a blood biomarker of LPS exposure with incident AMD.<br><br>METHODS: The Alienor Study is a prospective population-based study, including 963 residents of Bordeaux (France), aged 73&#xa0;years or more at baseline. Esterified 3-hydroxy fatty acids (3-OH FAs) were measured from blood samples as a proxy of LPS burden. AMD was graded from color retinal photographs and spectral domain optical coherence tomography, performed every two years from 2006 to 2017. Cox proportional hazards models were used to estimate associations of between esterified 3-OH FAs, using 722 eyes at risk for incident early AMD and 981 eyes at risk for incident advanced AMD.<br><br>RESULTS: Higher esterified 3-OH FAs were associated with incident early AMD after adjusting for age and gender (hazard ratio [HR] = 1.21 for 1 standard deviation [SD] increase; 95% confidence interval [CI], 1.01-1.45; P = 0.04) but not with incident advanced AMD (HR = 1.03 for 1 SD increase; 95% CI, 0.73-1.45; P = 0.86). These associations remained stable after multivariate adjustment and imputation for missing covariates (early AMD HR = 1.22 for 1 SD increase; 95% CI, 1.01-1.46; P = 0.04; advanced AMD HR = 0.98 for 1 SD increase; 95% CI, 0.69-1.38; P = 0.91).<br><br>CONCLUSIONS: This study evidenced an association between higher esterified 3-OH FAs and incident early AMD, suggesting that exposure to LPS may be involved in the early pathophysiological processes of AMD.},
}
@article {pmid38029849,
year = {2024},
author = {Nashine, S and Kenney, MC},
title = {Effects of Humanin G (HNG) on angiogenesis and neurodegeneration markers in Age-related Macular Degeneration (AMD).},
journal = {Mitochondrion},
volume = {74},
number = {},
pages = {101818},
doi = {10.1016/j.mito.2023.11.001},
pmid = {38029849},
issn = {1872-8278},
support = {R01 EY027363/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Angiogenesis ; Cell Line ; Intracellular Signaling Peptides and Proteins ; DNA, Mitochondrial/genetics ; *Macular Degeneration/genetics/metabolism/pathology ; },
abstract = {Advanced stages of Age-related Macular Degeneration (AMD) are characterized by retinal neurodegeneration and aberrant angiogenesis, and mitochondrial dysfunction contributes to the pathogenesis of AMD. In this study, we tested the hypothesis that Humanin G (HNG), a cytoprotective mitochondrial-derived peptide, positively regulates cell proliferation, cell death, and the protein levels of angiogenesis and neurodegeneration markers, in normal (control) and AMD RPE transmitochondrial cybrid cell lines. These normal and AMD RPE transmitochondrial cybrid cell lines had identical nuclei derived from mitochondria-deficient ARPE-19 cell line, but differed in mitochondrial DNA (mtDNA) content that was derived from clinically characterized AMD patients and normal (control) subjects. Cell lysates were extracted from untreated and HNG-treated AMD and normal (control) cybrid cell lines, and the Luminex XMAP multiplex assay was used to examine the protein levels of angiogenesis and neurodegeneration markers. Humanin G reduced Caspase-3/7-mediated apoptosis, improved cell proliferation, and normalized the protein levels of angiogenesis and neurodegeneration markers in AMD RPE cybrid cell lines, thereby suggesting Humanin G's positive regulatory role in AMD.},
}
@article {pmid38028508,
year = {2023},
author = {Kananen, F and Immonen, I},
title = {Retinal pigment epithelium-Bruch's membrane volume in grading of age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {16},
number = {11},
pages = {1827-1831},
pmid = {38028508},
issn = {2222-3959},
abstract = {AIM: To assess the agreement of optical coherence tomography (OCT) algorithm-based retinal pigment epithelium -Bruch's membrane complex volume (RBV) with fundus photograph-based age-related macular degeneration (AMD) grading.<br><br>METHODS: Digital color fundus photographs (CFPs) and spectral domain OCT images were acquired from 96 elderly subjects. CFPs were graded according to Age-Related Eye Disease Study (AREDS) classification. OCT image segmentation and RBV data calculation were done with Orion&#x2122; software. Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.<br><br>RESULTS: RBV correlated with AMD grading (rs=0.338, P=0.001), the correlation was slightly stronger in early AMD (n=52; rs=0.432, P=0.001). RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs (1.05&#xb1;0.20 vs 0.96&#xb1;0.13 mm[3], P=0.023). In multivariate analysis higher RBVs were associated significantly with higher total drusen (&#x3b2;=0.388, P=0.027) and pigmentation areas (&#x3b2;=0.319, P=0.020) in fundus photographs, whereas depigmentation area (&#x3b2;=-0.295, P=0.015) associated with lower RBV.<br><br>CONCLUSION: RBV correlate with AMD grading status, with a stronger association in patients with moderate, non-late AMD grades. This effect is driven mostly by lesions with drusen or pigmentation. Lesions with depigmentation tend to have lower values. RBV is more comprehensive measurement of the key area of AMD pathogenesis, compared to sole drusen volume analysis. RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting, but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.},
}
@article {pmid38027818,
year = {2023},
author = {Zhang, R and Wang, L and Li, Y and Gui, C and Pei, Y and Zhou, G},
title = {Roles and mechanisms of long non-coding RNAs in age-related macular degeneration.},
journal = {Heliyon},
volume = {9},
number = {11},
pages = {e22307},
pmid = {38027818},
issn = {2405-8440},
abstract = {Worldwide, age-related macular degeneration (AMD) is a multifactorial progressive fundus disorder that can cause vision impairment and severe central blindness in older adults. Currently, there are no approved prevention or treatment strategies for non-exudative AMD. While targeting VEGF is the main therapeutic approach to delay the degeneration process in exudative AMD, a significant number of patients show insensitivity or ineffectiveness to anti-VEGF therapy. Despite years of research, the exact mechanism underlying drusen formation and macular atrophy in AMD remains unknown. In the pathogenesis of AMD, lncRNAs play crucial roles, as discussed in this paper. This review focuses on the function of dysregulated lncRNAs and the mechanisms by which specific molecules target these lncRNAs in AMD. The analysis reveals that lncRNAs primarily regulate the progression of AMD by mediating apoptosis, epithelial-mesenchymal transition (EMT), dedifferentiation, and oxidative stress in choroidal vascular endothelial cells, retinal pigment epithelium (RPE) cells, and photoreceptors. Consequently, the regulation of apoptosis, dedifferentiation, EMT, and other processes by lncRNAs has emerged as a crucial focus in AMD research.These findings contribute to our understanding of the role of lncRNAs in AMD and their potential as valuable biomarkers. Furthermore, they highlight the need for further basic and clinical studies to explore the value of lncRNAs as biomarkers and potential therapeutic targets for AMD.},
}
@article {pmid38026609,
year = {2023},
author = {Agarwal, S and Thornell, E},
title = {YAG Capsulotomy Rates in Patients Following Cataract Surgery and Implantation of New Hydrophobic Preloaded Intraocular Lens in an Australian Cohort: 3-Year Results.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {3637-3643},
pmid = {38026609},
issn = {1177-5467},
abstract = {PURPOSE: To assess the risk of posterior capsular opacification (PCO) following implantation of the Clareon lens.<br><br>MATERIALS AND METHODS: Retrospective analysis was performed for 484 consecutive eyes that had undergone phacoemulsification and implantation of a monofocal lens (CNA0T) between April 2018 and February 2020. Eyes with other ocular pathology that may affect outcomes, previous refractive surgery or eyes corrected for a near target were excluded. Incidence of PCO and YAG capsulotomy was recorded and regression analysis was performed to determine risk factors associated with PCO formation.<br><br>RESULTS: Overall incidence of PCO following implantation of the CNA0T monofocal lens was 3.7% (18 eyes) at 1 year with 1.9% (9 eyes) undergoing YAG capsulotomy. At 3 years, 8.7% (42 eyes) had developed PCO and 4.1% (20 eyes) had undergone YAG capsulotomy cumulatively. Primary open angle glaucoma (POAG; OR = 6.53; 95% CI = 18.68, 2.28; P = 0.0005), age-related macular degeneration (AMD; OR = 2.35; 95% CI = 5.21, 1.06; P = 0.036), vitreomacular traction (VMT; OR = 7.32; 95% CI = 45.08, 1.19; P = 0.032), retinal vein occlusion (RVO; OR = 8.42; 95% CI = 38.99, 1.82; P = 0.006) and history of anti-VEGF therapy (OR = 3.22; 95% CI = 10.26, 1.01; P = 0.048) were positively associated with an increased risk of PCO.<br><br>CONCLUSIONS: Incidence of PCO requiring YAG capsulotomy was relatively low. However, certain co-morbidities were found to increase the risk of PCO development, most significantly POAG and RVO.},
}
@article {pmid38026599,
year = {2023},
author = {Coney, JM and McCoy, JE and Buxy Sinha, S and Sonbolian, N and Zhou, L and Hull, TP and Lewis, SA and Miller, DG and Novak, MA and Pendergast, SD and Pham, H and Platt, SM and Rao, LJ and Schartman, JP and Singerman, LJ and Donkor, R and Fink, M and Zubricky, R and Karcher, H},
title = {One-Year and 18-Month Outcomes in nAMD Patient Eyes Switched to Brolucizumab Alone versus to Brolucizumab Alternating with Other Anti-VEGF Agents.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {3601-3611},
pmid = {38026599},
issn = {1177-5467},
abstract = {OBJECTIVE: Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF.<br><br>METHODS: The overall study population comprised eyes that were given &#x2265;1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with &#x2265;3 brolucizumab injections over &#x2265;12 or &#x2265;18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with &#x2265;2 brolucizumab injections and &#x2265;1 other anti-VEGF over &#x2265;12 or &#x2265;18 months.<br><br>RESULTS: A total of 482 eyes received &#x2265;1 brolucizumab injection during the study period. Mean VA changes from baseline were -1.1&#xb1;15.1 letters (BRO cohort; n = 174) and 1.3&#xb1;13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0&#xb1;13.5 letters (BRO cohort; n = 95) and -7.3&#xb1;17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9&#xb1;48.1 days (BRO cohort) and +11.1&#xb1;17.3 days (ALT cohort) at Month 12 and +36.3&#xb1;52.3 days (BRO cohort) and +14.0&#xb1;19.9 days (ALT cohort) at Month 18. Mean changes in CMT were -35.2&#xb1;108.1 &#x3bc;m (BRO cohort) and -31.5&#xb1;91.2 &#x3bc;m (ALT cohort) at Month 12 and -38.9&#xb1;75.0 &#x3bc;m (BRO cohort) and -9.0&#xb1;59.9 &#x3bc;m (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes.<br><br>CONCLUSION: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD.},
}
@article {pmid38025159,
year = {2023},
author = {Cheong, KX and Li, H and Tham, YC and Teo, KYC and Tan, ACS and Schmetterer, L and Wong, TY and Cheung, CMG and Cheng, CY and Fan, Q},
title = {Relationship Between Retinal Layer Thickness and Genetic Susceptibility to Age-Related Macular Degeneration in Asian Populations.},
journal = {Ophthalmology science},
volume = {3},
number = {4},
pages = {100396},
pmid = {38025159},
issn = {2666-9145},
abstract = {PURPOSE: For OCT retinal thickness measurements to be used as a prodromal age-related macular degeneration (AMD) risk marker, the 3-dimensional (3D) topographic variation of the relationship between genetic susceptibility to AMD and retinal thickness needs to be assessed. We aimed to evaluate individual retinal layer thickness changes and topography at the macula that are associated with AMD genetic susceptibility.<br><br>DESIGN: Genetic association study.<br><br>PARTICIPANTS: A total of 1579 healthy participants (782 Chinese, 353 Malays, and 444 Indians) from the multiethnic Singapore Epidemiology of Eye Diseases study were included.<br><br>METHODS: Spectral-domain OCT and automatic segmentation of individual retinal layers were performed to produce 10 retinal layer thickness measurements at each ETDRS subfield, producing 3D topographic information. Age-related macular degeneration genetic susceptibility was represented via single nucleotide polymorphisms (SNPs) and aggregated via whole genome (overall) and pathway-specific age-related macular degeneration polygenic risk score (PRSAMD).<br><br>MAIN OUTCOME MEASURES: Associations of individual SNPs, overall PRSAMD, and pathway-specific PRSAMD with retinal thickness were analyzed by individual retinal layer and ETDRS subfield.<br><br>RESULTS: CFH rs10922109, ARMS2-HTRA1 rs3750846, and LIPC rs2043085 were the top AMD susceptibility SNPs associated with retinal thickness of individual layers (P&#xa0;<&#xa0;1.67&#xa0;&#xd7;&#xa0;10[-3]), all at the central subfield. The overall PRSAMD was most associated with thinner L9 (outer segment photoreceptor/retinal pigment epithelium complex) thickness at the central subfield (&#x3b2;&#xa0;=&#xa0;-0.63 &#x3bc;m; P&#xa0;=&#xa0;5.45&#xa0;&#xd7;&#xa0;10[-9]). Pathway-specific PRSAMD for the complement cascade (&#x3b2;&#xa0;=&#xa0;-0.53 &#x3bc;m; P&#xa0;=&#xa0;9.42&#xa0;&#xd7;&#xa0;10[-7]) and lipoprotein metabolism (&#x3b2;&#xa0;=&#xa0;-0.05 &#x3bc;m; P&#xa0;=&#xa0;0.0061) were associated with thinner photoreceptor layers (L9 and L7 [photoreceptor inner/outer segments], respectively) at the central subfield. The mean PRSAMD score was larger among Indians compared with that of the Chinese and had the thinnest thickness at the L9 central subfield (&#x3b2;&#xa0;=&#xa0;-1.00 &#x3bc;m; P&#xa0;=&#xa0;2.91&#xa0;&#xd7;&#xa0;10[-7]; R[2]&#xa0;=&#xa0;5.5%). Associations at other retinal layers and ETDRS regions were more heterogeneous.<br><br>CONCLUSIONS: Overall genetic susceptibility to AMD and the aggregate effects of the complement cascade and lipoprotein metabolism pathway are associated most significantly with L7 and L9 photoreceptor thinning at the central macula in healthy individuals. Photoreceptor thinning has potential to be a prodromal AMD risk marker, and topographic variation should be considered.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid38024137,
year = {2023},
author = {Al-Hinnawi, AR and Al-Latayfeh, M and Tavakoli, M},
title = {Innovative Macula Capillaries Plexuses Visualization with OCTA B-Scan Graph Representation: Transforming OCTA B-Scan into OCTA Graph Representation.},
journal = {Journal of multidisciplinary healthcare},
volume = {16},
number = {},
pages = {3477-3491},
pmid = {38024137},
issn = {1178-2390},
abstract = {PURPOSE: The aim of this study is to transform optical coherence tomography angiography (OCTA) scans into innovative OCTA graphs, serving as novel biomarkers representing the macular vasculature.<br><br>PATIENTS AND METHODS: The study included 90 healthy subjects and 39 subjects with various abnormalities (29 with diabetic retinopathy, 5 with age-related macular degeneration, and 5 with choroid neovascularization). OCTA 5&#xb5;m macular coronal views (MCVs) were generated for each subject, followed by blood vessel segmentation and skeleton processing. Subsequently, the blood vessel density index, blood vessel skeleton index, and blood vessel tortuosity index were computed. The graphs of each metric were plotted against the axial axes of the OCTA B-scan, representing the integrity of vasculature at successive 5&#xb5;m macular depths.<br><br>RESULTS: The results revealed two significant findings. First, the B-scans from OCTA can be transformed into OCTA graphs, yielding three specific OCTA graphs in this study. These graphs provide new biomarkers for assessing the integrity of deep vascular complex (DVC) and superficial vascular complex (SVC) within the macula. Second, a statistically significant difference was observed between normal (n=90) and abnormal (n=39) subjects, with a t-test p-value significantly lower than 0.001. The Mann-Whitney u-test also yielded significant difference but only between the 90 normal and 29 DR subjects.<br><br>CONCLUSION: The novel OCTA graphs offer a unique representation of the macula's SVC and DVC, suggesting their potential in aiding physicians in the diagnosis of eye health within OCTA clinics. Further research is warranted to finalize the shape of these newly derived OCTA graphs and establish their clinical relevance and utility.},
}
@article {pmid38023710,
year = {2023},
author = {Zhu, S and Fan, S and Tang, T and Huang, J and Zhou, H and Huang, C and Chen, Y and Qian, F},
title = {Polymorphic nanobody crystals as long-acting intravitreal therapy for wet age-related macular degeneration.},
journal = {Bioengineering &amp; translational medicine},
volume = {8},
number = {6},
pages = {e10523},
pmid = {38023710},
issn = {2380-6761},
abstract = {Wet age-related macular degeneration (wet AMD) is the most common cause of blindness, and chronic intravitreal injection of anti-vascular endothelial growth factor (VEGF) proteins has been the dominant therapeutic approach. Less intravitreal injection and a prolonged inter-injection interval are the main drivers behind new wet AMD drug innovations. By rationally engineering the surface residues of a model anti-VEGF nanobody, we obtained a series of anti-VEGF nanobodies with identical protein structures and VEGF binding affinities, while drastically different crystallization propensities and crystal lattice structures. Among these nanobody crystals, the P212121 lattice appeared to be denser and released protein slower than the P1 lattice, while nanobody crystals embedding zinc coordination further slowed the protein release rate. The polymorphic protein crystals could be a potentially breakthrough strategy for chronic intravitreal administration of anti-VEGF proteins.},
}
@article {pmid38023610,
year = {2023},
author = {Ueta, Y and Kamada, R and Watanabe, Y and Tanaka, N},
title = {Marked Choroidal Thinning Observed after Intravitreal Brolucizumab Injection.},
journal = {Case reports in ophthalmology},
volume = {14},
number = {1},
pages = {620-625},
pmid = {38023610},
issn = {1663-2699},
abstract = {INTRODUCTION: Here, we report a case of severe intraocular inflammation (IOI) and prominent choroidal thinning following the initial intravitreal brolucizumab injection (IVBr).<br><br>CASE PRESENTATION: The patient was a 75-year-old Japanese man with type 2 age-related macular degeneration of both eyes. Until 2015, he had undergone two intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and two photodynamic therapies in his right eye. His decimal best-corrected visual acuity (BCVA) was 0.1 in the right eye and 0.1 in the left eye. Central choroidal thickness (CCT) measured 240 &#x3bc;m in his right eye. IVBr was administered to the right eye. The patient reported pain in the right eye 23 days after the injection. On day 26, panuveitis and retinal vasculitis were observed in the right eye. CCT measured 436 &#x3bc;m. On the same day, a sub-tenon triamcinolone injection was administered. On day 42, retinal inflammation remained at a similar level. The CCT decreased to 164 &#x3bc;m. On day 68, the intraocular pressure (IOP) in the right eye increased to 39 mm Hg, and IOI persisted. On day 89, the patient's eye pain disappeared, and the IOP decreased to 13 mm Hg. On day 225, the IOI and symptoms were completely resolved. The decimal BCVA was 0.04 in the right eye, and CCT measured 84 &#x3bc;m.<br><br>CONCLUSION: Brolucizumab is a highly effective anti-VEGF drug; however, it has the potential to induce inflammation in tissues adjacent to the retina and may occasionally cause irreversible sequelae.},
}
@article {pmid38022794,
year = {2023},
author = {Binczyk, NM and Plemel, DJA and Seamone, M and Rudnisky, CJ and Tennant, MTS},
title = {Decrease in Anti-VEGF Injections After Post-injection Endophthalmitis in Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {6},
pages = {528-532},
pmid = {38022794},
issn = {2474-1272},
abstract = {Introduction: To evaluate the effect of antivascular endothelial growth factor (anti-VEGF)-related endophthalmitis on intravitreal injection (IVI) frequency in patients with neovascular age-related macular degeneration (nAMD). Methods: A retrospective chart review was performed of all cases of post IVI endophthalmitis that occurred in Edmonton, Alberta, Canada, between 2012 and 2019. Contralateral eyes affected by nAMD but without endophthalmitis served as a control group. The main outcome measures were the frequency of anti-VEGF injections, visual acuity, and activity of choroidal neovascularization before and after endophthalmitis. Results: Seventeen eyes met the inclusion criteria, 2 (12%) of which never resumed IVI after endophthalmitis because of the quiescence of disease. Post-endophthalmitis eyes received IVI less frequently in the 1 year after endophthalmitis (mean 0.52 ± 0.42 IVI/month) than those that received IVI 1 year before endophthalmitis (1.09 ± 0.36 IVI/month) (P = .001). The 17 contralateral eyes also received anti-VEGF injections less frequently after endophthalmitis than before (P = .001). There was no significant change in optical coherence tomography markers of disease activity in cases or controls. Conclusions: In patients with nAMD, endophthalmitis resolution is associated with a decrease in anti-VEGF injection frequency. The same decrease in anti-VEGF injection frequency is also seen in contralateral eyes unaffected by endophthalmitis. Markers of disease activity remain unchanged in both eyes, suggesting disease quiescence despite reduced IVI frequency.},
}
@article {pmid38021969,
year = {2023},
author = {Kulkarni, A and Banait, S},
title = {Through the Smoke: An In-Depth Review on Cigarette Smoking and Its Impact on Ocular Health.},
journal = {Cureus},
volume = {15},
number = {10},
pages = {e47779},
pmid = {38021969},
issn = {2168-8184},
abstract = {Smoking is a widespread and pervasive habit, impacting health across various care settings, including acute care, subacute care, home-based care, and long-term care. Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. Cigarette smoke contains a complex mixture of harmful constituents, including nicotine and toxic chemicals, which permeate the bloodstream, affecting ocular tissues. The oxidative stress and inflammation induced by smoking are central to its detrimental effects on ocular health. Age-related macular degeneration (AMD), a leading cause of vision loss, exhibits a strong association with smoking. Research consistently demonstrates that smokers face a heightened risk of both early and advanced AMD. Cataracts, another prevalent ocular condition, develop earlier and progress more rapidly in smokers. The oxidative stress on the lens and reduced antioxidants among smokers contribute to the increased severity of cataracts. Moreover, the health of the eyes may be compromised by smoking-related chemicals that reduce blood flow and/or hasten thrombus formation in ocular capillaries thus increasing the chance of acquiring glaucoma, cataracts, AMD, and Graves' eye disease. Beyond individual health concerns, the societal implications of smoking on ocular health are substantial, including increased healthcare costs and diminished quality of life for affected individuals. Understanding the underlying mechanisms can provide insights into potential therapeutic interventions for preventing and managing smoking-related ocular damage. Given the global prevalence of smoking, raising awareness about the ocular risks associated with smoking is crucial for promoting eye health. The review underscores the urgent need for comprehensive anti-smoking initiatives and smoking cessation programs to alleviate the burden of ocular diseases associated with smoking.},
}
@article {pmid38019527,
year = {2024},
author = {Aggarwal, S and Moir, J and Hyman, MJ and Kaufmann, GT and Flores, A and Hariprasad, SM and Skondra, D},
title = {Metformin Use and Age-Related Macular Degeneration in Patients Without Diabetes.},
journal = {JAMA ophthalmology},
volume = {142},
number = {1},
pages = {53-57},
pmid = {38019527},
issn = {2168-6173},
mesh = {Aged ; Female ; Humans ; Case-Control Studies ; *Diabetes Mellitus/drug therapy ; *Geographic Atrophy/drug therapy ; Hypoglycemic Agents/therapeutic use ; *Macular Degeneration/diagnosis/epidemiology/drug therapy ; Medicare ; *Metformin/therapeutic use ; Prospective Studies ; Risk Factors ; United States/epidemiology ; Male ; Aged, 80 and over ; Middle Aged ; },
abstract = {IMPORTANCE: Metformin use may protect against the development of age-related macular degeneration (AMD) based on results from observational studies. However, its potential effectiveness among patients without diabetes remains unclear.<br><br>OBJECTIVE: To assess the association between metformin use and the development of AMD in patients without diabetes.<br><br>This case-control study used data from 2006 to 2017 in the Merative MarketScan Research Database, a nationwide insurance claims database that includes between 27 and 57 million patients in the US with primary or Medicare supplemental health insurance. Cases with AMD and controls without AMD aged 55 years or older were matched 1:1 by year, age, anemia, hypertension, region, and Charlson Comorbidity Index score. Then, cases and matched controls without a diagnosis of diabetes were selected. In subgroup analyses, cases with dry AMD and their matched controls were identified to explore the association between metformin use and AMD staging in patients without diabetes. Data were analyzed between March and September 2023.<br><br>EXPOSURES: Exposure to metformin in the 2 years prior to the index date (ie, date of AMD diagnosis in cases and date of a randomly selected eye examination for controls) was assessed from the claims database and categorized into quartiles based on cumulative dose (1-270, 271-600, 601-1080, and >1080 g/2 y). Exposure to other antidiabetic medications was also noted.<br><br>MAIN OUTCOMES AND MEASURES: Odds of new-onset AMD development as assessed by multivariable conditional logistic regression after adjusting for known risk factors for AMD, including female sex, hyperlipidemia, smoking, and exposures to other antidiabetic medications. Asymptotic Cochran-Armitage tests for trend were also performed.<br><br>RESULTS: We identified 231&#x202f;142 patients with any AMD (mean [SD] age, 75.1 [10.4] years; 140 172 females [60.6%]) and 232 879 matched controls without AMD (mean [SD] age, 74.9 [10.5] years; 133 670 females [57.4%]), none of whom had a diagnosis of diabetes. The sample included 144 147 cases with dry AMD that were matched to 144 530 controls. In all, 2268 (1.0%) cases and 3087 controls (1.3%) were exposed to metformin in the 2 years before their index visit. After data adjustment, exposure to any metformin was associated with reduced odds of any AMD development (adjusted odds ratio [AOR], 0.83; 95% CI, 0.74-0.87), specifically in the dosing quartiles of 1 to 270, 271 to 600, and 601 to 1080 g/2 y. Any metformin use was also associated with a reduced odds of developing dry AMD (AOR, 0.85; 95% CI, 0.79-0.92), specifically in the dosing quartiles of 1 to 270 and 271 to 600 g/2 y. Adjusted odds ratios for any AMD and dry AMD development did not differ across the dosing quartiles. Asymptotic Cochran-Armitage tests for trend revealed 2-sided P&#x2009;=&#x2009;.51 and P&#x2009;=&#x2009;.66 for the any and dry AMD samples, respectively.<br><br>CONCLUSIONS AND RELEVANCE: In this case-control study of a population without a diagnosis of diabetes, metformin use was associated with reduced odds of developing AMD. This association does not appear to be dose dependent. These findings provide further impetus to study metformin's usefulness in protecting against AMD in prospective clinical trials.},
}
@article {pmid38019503,
year = {2024},
author = {Li, Y and Yip, M and Ning, Y and Chung, J and Toh, A and Leow, C and Liu, N and Ting, D and Schmetterer, L and Saw, SM and Jonas, JB and Chia, A and Ang, M},
title = {Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study.},
journal = {JAMA ophthalmology},
volume = {142},
number = {1},
pages = {15-23},
pmid = {38019503},
issn = {2168-6173},
support = {/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Female ; Infant ; Male ; Atropine/administration &amp; dosage ; Prospective Studies ; Ophthalmic Solutions/administration &amp; dosage ; Administration, Topical ; Refraction, Ocular ; *Myopia, Degenerative/drug therapy ; *Cataract ; *Myopia ; *Genetic Diseases, X-Linked ; },
abstract = {IMPORTANCE: Clinical trial results of topical atropine eye drops for childhood myopia control have shown inconsistent outcomes across short-term studies, with little long-term safety or other outcomes reported.<br><br>OBJECTIVE: To report the long-term safety and outcomes of topical atropine for childhood myopia control.<br><br>This prospective, double-masked observational study of the Atropine for the Treatment of Myopia (ATOM) 1 and ATOM2 randomized clinical trials took place at 2 single centers and included adults reviewed in 2021 through 2022 from the ATOM1 study (atropine 1% vs placebo; 1999 through 2003) and the ATOM2 study (atropine 0.01% vs 0.1% vs 0.5%; 2006 through 2012).<br><br>MAIN OUTCOME MEASURES: Change in cycloplegic spherical equivalent (SE) with axial length (AL); incidence of ocular complications.<br><br>RESULTS: Among the original 400 participants in each original cohort, the study team evaluated 71 of 400 ATOM1 adult participants (17.8% of original cohort; study age, mean [SD] 30.5 [1.2] years; 40.6% female) and 158 of 400 ATOM2 adult participants (39.5% of original cohort; study age, mean [SD], 24.5 [1.5] years; 42.9% female) whose baseline characteristics (SE and AL) were representative of the original cohort. In this study, evaluating ATOM1 participants, the mean (SD) SE and AL were -5.20 (2.46) diopters (D), 25.87 (1.23) mm and -6.00 (1.63) D, 25.90 (1.21) mm in the 1% atropine-treated and placebo groups, respectively (difference of SE, 0.80 D; 95% CI, -0.25 to 1.85 D; P&#x2009;=&#x2009;.13; difference of AL, -0.03 mm; 95% CI, -0.65 to 0.58 mm; P&#x2009;=&#x2009;.92). In ATOM2 participants, the mean (SD) SE and AL was -6.40 (2.21) D; 26.25 (1.34) mm; -6.81 (1.92) D, 26.28 (0.99) mm; and -7.19 (2.87) D, 26.31 (1.31) mm in the 0.01%, 0.1%, and 0.5% atropine groups, respectively. There was no difference in the 20-year incidence of cataract/lens opacities, myopic macular degeneration, or parapapillary atrophy (&#x3b2;/&#x3b3; zone) comparing the 1% atropine-treated group vs the placebo group.<br><br>CONCLUSIONS AND RELEVANCE: Among approximately one-quarter of the original participants, use of short-term topical atropine eye drops ranging from 0.01% to 1.0% for a duration of 2 to 4 years during childhood was not associated with differences in final refractive errors 10 to 20 years after treatment. There was no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group vs the placebo group. These findings may affect the design of future clinical trials, as further studies are required to investigate the duration and concentration of atropine for childhood myopia control.},
}
@article {pmid38019498,
year = {2023},
author = {Hunter, AML and Anderson, RS and Redmond, T and Garway-Heath, DF and Mulholland, PJ},
title = {Investigating the Spatiotemporal Summation of Perimetric Stimuli in Dry Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {11},
pages = {37},
pmid = {38019498},
issn = {2164-2591},
mesh = {Humans ; Aged ; *Visual Field Tests ; *Geographic Atrophy/diagnosis ; },
abstract = {PURPOSE: To measure achromatic spatial, temporal, and spatiotemporal summation in dry age-related macular degeneration (AMD) compared to healthy controls under conditions of photopic gaze-contingent perimetry.<br><br>METHODS: Twenty participants with dry AMD (mean age, 74.6 years) and 20 healthy controls (mean age, 67.8 years) performed custom, gaze-contingent perimetry tests. An area-modulation test generated localized estimates of Ricco's area (RA) at 2.5&#xb0; and 5&#xb0; eccentricities along the 0&#xb0;, 90&#xb0;, 180&#xb0;, and 270&#xb0; meridians. Contrast thresholds were measured at the same test locations for stimuli of six durations (3.7-190.4 ms) with a Goldmann III stimulus (GIII, 0.43&#xb0;) and RA-scaled stimuli. The upper limit (critical duration) of complete temporal summation (using the GIII stimulus) and spatiotemporal summation (using the RA stimuli) was estimated using iterative two-phase regression analysis.<br><br>RESULTS: Median (interquartile range [IQR]) RA estimates were significantly larger in AMD participants (2.5&#xb0;: 0.21 [0.09-0.41] deg2; 5&#xb0;: 0.32 [0.15-0.65 deg2]) compared to healthy controls (2.5&#xb0;: 0.08 [0.05-0.13] deg2; 5&#xb0;: 0.15 [0.08-0.22] deg2) at all test locations (all P < 0.05). No significant difference in median critical duration was found in AMD participants with the GIII stimulus (19.6 [9.9-30.4] ms) and RA-scaled stimuli (22.9 [13.9-40.3] ms) compared to healthy controls (GIII: 17.0 [11.3-24.0] ms; RA-scaled: 22.4 [14.3-33.1] ms) at all test locations (all P > 0.05).<br><br>CONCLUSIONS: Spatial summation is altered in dry AMD, without commensurate changes in temporal summation.<br><br>TRANSLATIONAL RELEVANCE: The sensitivity of perimetry to AMD may be improved by utilizing stimuli that probe alterations in spatial summation in the disease.},
}
@article {pmid38018801,
year = {2024},
author = {Mahmoudinezhad, G and Meller, L and Moghimi, S},
title = {Impact of smoking on glaucoma.},
journal = {Current opinion in ophthalmology},
volume = {35},
number = {2},
pages = {124-130},
pmid = {38018801},
issn = {1531-7021},
support = {R01 EY029058/EY/NEI NIH HHS/United States ; R01 EY034148/EY/NEI NIH HHS/United States ; T35 EY033704/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Smoking ; *Glaucoma, Open-Angle ; Intraocular Pressure ; *Glaucoma/complications ; Risk Factors ; },
abstract = {PURPOSE OF REVIEW: Assessing whether lifestyle related factors play a role in causing primary open-angle glaucoma (POAG) is of great value to clinicians, public health experts and policy makers. Smoking is a major global public health concern and contributes to ocular diseases such as cataracts, and age-related macular degeneration through ischemic and oxidative mechanisms. Recently, smoking has been investigated as a modifiable risk factor for glaucoma. In the presence of an association with glaucoma, provision of advice and information regarding smoking to patients may help reduce the burden of disease caused by POAG. Therefore, the aim of this review is to summarize the current evidence regarding the effect of smoking in the pathogenesis of glaucoma and its incidence, progression as well as the benefits of smoking cessation.<br><br>RECENT FINDINGS: While the association between glaucoma development and smoking history is controversial, in the last decade, several recent studies have helped to identify possible effects of smoking, especially heavy smoking, in regard to glaucomatous progression. Smoking cessation may possibly be protective against glaucoma progression.<br><br>SUMMARY: Smoking may play a role in glaucoma progression and long-term smoking cessation may be associated with lower glaucoma progression. The dose-response relationship between smoking and glaucoma as well as therapeutic potential of smoking cessation needs to be further validated with both preclinical and rigorous clinical studies.},
}
@article {pmid38018728,
year = {2023},
author = {Bek, T and Sørensen, TL},
title = {[Not Available].},
journal = {Ugeskrift for laeger},
volume = {185},
number = {48},
pages = {},
pmid = {38018728},
issn = {1603-6824},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Retina ; },
abstract = {This review investigates age-related macular degeneration (AMD) which is a degenerative retinal disease. The pathogenesis of the disease is unknown, but tobacco smoking is a significant risk factor for the development of the disease. The wet form of AMD can be treated by intraocular injection of an antibody that binds vascular endothelial growth factor (VEGF) which is involved in the disease process. The introduction of anti-VEGF treatment is a major reason why blindness secondary to wet AMD is now negligible. The demographic development can be expected to increase the demand for treatment of AMD considerably in the future.},
}
@article {pmid38018727,
year = {2023},
author = {Grauslund, J and Vorum, H},
title = {[Not Available].},
journal = {Ugeskrift for laeger},
volume = {185},
number = {48},
pages = {},
pmid = {38018727},
issn = {1603-6824},
mesh = {Humans ; Artificial Intelligence ; *Diabetic Retinopathy/diagnostic imaging ; *Eye Diseases/diagnosis ; Algorithms ; *Ophthalmology/methods ; },
abstract = {As ophthalmology is an increasingly busy medical specialty relying solidly on imaging technology, this review investigates the introduction of artificial intelligence to improve diagnostic performance and reduce human resources. In diabetic retinopathy screening, algorithms are now regulatory-approved for international markets but not yet tailored for the Danish system. In age-related macular degeneration, algorithms are now able to facilitate the classification and segmentation of disease activity, and in upcoming years, these are likely to assist us to improve diagnosis and provide subsequent clinical care.},
}
@article {pmid38017101,
year = {2024},
author = {Crisostomo, KGR and Dantes, JKPC and Magpantay, DMM and Artiaga, JCM},
title = {Infographic: intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration (VIEW 1 and VIEW 2).},
journal = {Eye (London, England)},
volume = {38},
number = {Suppl 2},
pages = {49-50},
pmid = {38017101},
issn = {1476-5454},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors/therapeutic use ; *Intravitreal Injections ; *Recombinant Fusion Proteins/therapeutic use/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
}
@article {pmid38016793,
year = {2023},
author = {Thinggaard, BS and Pedersen, M and Sorensen, TL and Grauslund, J and Stokholm, L},
title = {Patient perspectives and barriers in the treatment of neovascular age-related macular degeneration in Denmark: a qualitative study.},
journal = {BMJ open},
volume = {13},
number = {11},
pages = {e077175},
pmid = {38016793},
issn = {2044-6055},
mesh = {Humans ; Aged ; *Angiogenesis Inhibitors/therapeutic use ; Quality of Life ; Patient Satisfaction ; *Macular Degeneration/drug therapy ; Denmark ; Intravitreal Injections ; Ranibizumab ; },
abstract = {OBJECTIVES: This qualitative study aims to identify patient-reported barriers to treatment for neovascular age-related macular degeneration (nAMD) and investigate their impact on quality of life.<br><br>DESIGN: Using a qualitative explorative design.<br><br>SETTING: Semi-structured individual or dyadic interviews were conducted with patients and their relatives.<br><br>PARTICIPANTS: Twenty-one patients completed the interview, with four of them having a relative present.<br><br>INTERVENTIONS: Gadamer's hermeneutics guided the epistemological approach, and maximum variation sampling was employed to capture diverse patient experiences. An advisory board consisting of patients, relatives and ophthalmologists ensured the relevance of the study. Thematic analysis was conducted using NVivo software.<br><br>To investigate patient-reported barriers to the recommended treatment for nAMD and impact on quality of life.<br><br>RESULTS: The study included 21 patients with nAMD, with a median age of 79 years. Five themes emerged: (1) good compliance with intravitreal treatment, (2) the dual role of relatives, (3) treatment commute, (4) hospital barriers, (5) preventive health literacy.<br><br>CONCLUSION: This study highlights the resilience and adherence of patients with nAMD in Denmark to their treatment despite various barriers. While the therapy may have negative effects on their well-being, patients do not opt out of treatment. These findings underscore the importance of personalised treatment plans that provide, for example, convenient access to care and clear future agreements at the hospital. By adopting more patient-centred approaches, healthcare providers can enhance patient satisfaction and improve treatment adherence, ultimately leading to better patient outcomes and quality of life.},
}
@article {pmid38016431,
year = {2023},
author = {Ansari, G and Schärer, N and Camenzind Zuche, H and Gabrani, C and Anders, P and Pfau, K and Valmaggia, P and Giani, A and Esmaeelpour, M and Chingning Yamaguchi, T and Prünte, CF and Maloca, PM and Schmetterer, L and Scholl, HPN and Pfau, M},
title = {The Optical Coherence Tomography and Microperimetry Biomarker Evaluation in Patients with Geographic Atrophy (OMEGA) Study: Design and Baseline Characteristics - OMEGA Report 1.},
journal = {Ophthalmic research},
volume = {66},
number = {1},
pages = {1392-1401},
doi = {10.1159/000535375},
pmid = {38016431},
issn = {1423-0259},
mesh = {Humans ; Fluorescein Angiography ; Follow-Up Studies ; *Geographic Atrophy/diagnosis ; Prospective Studies ; Reproducibility of Results ; Tomography, Optical Coherence/methods ; Vision Disorders ; Visual Field Tests/methods ; Visual Fields ; },
abstract = {INTRODUCTION: The aim of this study was to describe the design and the participants' baseline characteristics of a prospective natural history study of geographic atrophy (GA) secondary to age-related macular degeneration.<br><br>METHODS: The optical coherence tomography (OCT) and microperimetry biomarker evaluation in patients with GA (OMEGA) study was conducted at a tertiary referral center (ClinicalTrials.gov identifier: NCT05963646). Participants were followed for 12 months during 4 visits (baseline and follow-up exams at weeks 12, 24, and 48) with best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity, low-luminance visual acuity (LLVA), and quick contrast sensitivity function testing. Further, participants underwent spectral-domain OCT, OCT angiography, fundus autofluorescence imaging, and mesopic microperimetry testing.<br><br>RESULTS: Thirty participants (median [IQR] age of 79 [77, 84] years) and 37 study eyes were included with a (median [IQR]) GA area of 1.40 mm2 (0.49, 5.24) at baseline. Out of 37 study eyes, six developed macular neovascularizations (16%). The study-eye best-corrected visual acuity was (median [IQR]) 0.18 logarithm of the minimum angle of resolution (logMAR) (0.06, 0.26), LLVA 0.66 logMAR (0.36, 0.88), and the microperimetry mean sensitivity 18.4 dB (9.21, 20.9). The highest correlation between square root GA area and a visual function test was evident for LLVA (R2 of 0.578), followed by area under the log contrast sensitivity function curve (0.519) and microperimetral retinal sensitivity (0.487).<br><br>CONCLUSION: This report lays out the design and baseline characteristics of the OMEGA study, which aims to contribute to the understanding of the natural history of GA. The OMEGA study will provide estimates of the ability to detect change and retest reliability for a panel of structure and functional assessments.},
}
@article {pmid38016089,
year = {2024},
author = {Inoda, S and Takahashi, H and Maruyama-Inoue, M and Ikeda, S and Sekiryu, T and Itagaki, K and Matsumoto, H and Mukai, R and Nagai, Y and Ohnaka, M and Kusuhara, S and Miki, A and Okada, AA and Nakayama, M and Nishiguchi, KM and Takeuchi, J and Mori, R and Tanaka, K and Honda, S and Kohno, T and Koizumi, H and Miyara, Y and Inoue, Y and Takana, H and Iida, T and Maruko, I and Hayashi, A and Ueda-Consolvo, T and Yanagi, Y},
title = {INCIDENCE AND RISK FACTORS OF INTRAOCULAR INFLAMMATION AFTER BROLUCIZUMAB TREATMENT IN JAPAN: A Multicenter Age-Related Macular Degeneration Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {4},
pages = {714-722},
doi = {10.1097/IAE.0000000000004009},
pmid = {38016089},
issn = {1539-2864},
mesh = {Female ; Humans ; Angiogenesis Inhibitors ; *Antibodies, Monoclonal, Humanized ; Incidence ; Inflammation ; Intravitreal Injections ; Japan ; *Macular Degeneration ; Retina ; *Retinal Vasculitis ; Risk Factors ; *Uveitis ; Vision Disorders ; Male ; },
abstract = {PURPOSE: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan.<br><br>METHODS: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors.<br><br>RESULTS: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset.<br><br>CONCLUSION: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.},
}
@article {pmid38015309,
year = {2024},
author = {Joseph, A and Bullimore, M and Drawnel, F and Miranda, M and Morgan, Z and Wang, YZ},
title = {Remote Monitoring of Visual Function in Patients with Maculopathy: The Aphelion Study.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {1},
pages = {409-422},
pmid = {38015309},
issn = {2193-8245},
abstract = {INTRODUCTION: Remote monitoring of vision, using tools such as the shape discrimination hyperacuity (SDH) test, can detect disease activity in patients with maculopathy. We determined the in-clinic accuracy and repeatability of three myVisionTrack expanded version (mVTx) tests for self-testing of visual acuity (VA) and contrast sensitivity.<br><br>METHODS: Aphelion, a single-arm, prospective study conducted at two sites in the USA, included adults with any maculopathy and a baseline VA of 0.7 log of minimum angle of resolution (logMAR) (Snellen 20/100) or better. Participants completed the mVTx tests (tumbling&#xa0;E, Landolt&#xa0;C, contrast sensitivity, and SDH) and standard clinical tests (near and distance Early Treatment Diabetic Retinopathy Study [ETDRS] charts and the Pelli-Robson contrast sensitivity chart). Test-retest repeatability and agreement between the mVTx tests and the corresponding clinical test were assessed by Bland-Altman analyses. Participants also completed a usability survey.<br><br>RESULTS: The mean age of the 122 participants was 67&#xa0;years. The most common diagnosis was age-related macular degeneration (42% of patients). The tumbling&#xa0;E test had a test-retest 95% limit of agreement (LoA) of &#xb1;&#x2009;0.18&#xa0;logMAR; the Landolt&#xa0;C test, &#xb1;&#x2009;0.23&#xa0;logMAR; the SDH test, &#xb1;&#x2009;0.24&#xa0;logMAR; and the contrast sensitivity test, &#xb1;&#x2009;0.32 log contrast threshold (logCT). Compared with the distance ETDRS chart, the LoA was &#xb1;&#x2009;0.35&#xa0;logMAR for the tumbling&#xa0;E test (mean difference,&#x2009;-&#x2009;0.07&#xa0;logMAR) and&#x2009;&#xb1;&#x2009;0.39&#xa0;logMAR for the Landolt&#xa0;C test (mean difference, 0.03&#xa0;logMAR). For the contrast sensitivity test, the LoA compared with the Pelli-Robson chart was &#xb1;&#x2009;0.30 logCT (mean difference,&#x2009;-&#x2009;0.25&#xa0;logCT). Most participants (85%) reported that they learned the tests quickly. The tumbling&#xa0;E test scored the highest on ease of use.<br><br>CONCLUSION: The mVTx tests of VA are accurate and repeatable, supporting their potential use alongside the SDH test to detect disease progression remotely between clinic visits.},
}
@article {pmid38014146,
year = {2023},
author = {Muqit, M and Mer, YL and de Koo, LO and Holz, FG and Sahel, JA and Palanker, D},
title = {Prosthetic Visual Acuity with the PRIMA System in Patients with Atrophic Age-related Macular Degeneration at 4 years follow-up.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {38014146},
support = {R01 EY027786/EY/NEI NIH HHS/United States ; },
abstract = {OBJECTIVE: To assess the efficacy and safety of the PRIMA subretinal neurostimulation system 48-months post-implantation for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months post-implantation.<br><br>DESIGN: First-in-human clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.gov NCT03333954).<br><br>SUBJECTS: Five patients with GA, no foveal light perception and VA of logMAR 1.3 to 1.7 in their worse-seeing "study" eye.<br><br>METHODS: In patients implanted with a subretinal photovoltaic neurostimulation array containing 378 pixels of 100 &#x3bc;m in size, the VA was measured with and without the PRIMA system using ETDRS charts at 1 meter. The system's external components: augmented reality glasses and pocket computer, provide image processing capabilities, including zoom.<br><br>MAIN OUTCOME MEASURES: VA using ETDRS charts with and without the system. Light sensitivity in the central visual field, as measured by Octopus perimetry. Anatomical outcomes demonstrated by fundus photography and optical coherence tomography up to 48-months post-implantation.<br><br>RESULTS: All five subjects met the primary endpoint of light perception elicited by the implant in the scotoma area. In one patient the implant was incorrectly inserted into the choroid. One subject died 18-months post-implantation due to study-unrelated reason. ETDRS VA results for the remaining three subjects are reported herein. Without zoom, VA closely matched the pixel size of the implant: 1.17 &#xb1; 0.13 pixels, corresponding to mean logMAR 1.39, or Snellen 20/500, ranging from 20/438 to 20/565. Using zoom at 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (SE 5.1) 95% CI[13.4,49.9], p<0.0001. Natural peripheral visual function in the treated eye did not decline after surgery compared to the fellow eye (p=0.08) during the 48 months follow-up period.<br><br>CONCLUSIONS: Subretinal implantation of PRIMA in subjects with GA suffering from profound vision loss due to AMD is feasible and well tolerated, with no reduction of natural peripheral vision up to 48-months. Using prosthetic central vision through photovoltaic neurostimulation, patients reliably recognized letters and sequences of letters,and with zoom it provided a clinically meaningful improvement in VA of up to eight ETDRS lines.},
}
@article {pmid38013069,
year = {2024},
author = {Manai, F and Smedowski, A and Kaarniranta, K and Comincini, S and Amadio, M},
title = {Extracellular vesicles in degenerative retinal diseases: A new therapeutic paradigm.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {365},
number = {},
pages = {448-468},
doi = {10.1016/j.jconrel.2023.11.035},
pmid = {38013069},
issn = {1873-4995},
mesh = {Humans ; Quality of Life ; *Extracellular Vesicles/metabolism ; Biomarkers/metabolism ; Retina/metabolism ; *Retinal Diseases/drug therapy/metabolism ; *Eye Diseases/drug therapy/metabolism ; },
abstract = {Nanoscale extracellular vesicles (EVs), consisting of exomers, exosomes and microvesicles/ectosomes, have been extensively investigated in the last 20 years, although their biological role is still something of a mystery. EVs are involved in the transfer of lipids, nucleic acids and proteins from donor to recipient cells or distant organs as well as regulating cell-cell communication and signaling. Thus, EVs are important in intercellular communication and this is not limited to sister cells, but may also mediate the crosstalk between different cell types even over long distances. EVs play crucial functions in both cellular homeostasis and the pathogenesis of diseases, and since their contents reflect the status of the donor cell, they represent an additional valuable source of information for characterizing complex biological processes. Recent advances in isolation and analytical methods have led to substantial improvements in both characterizing and engineering EVs, leading to their use either as novel biomarkers for disease diagnosis/prognosis or even as novel therapies. Due to their capacity to carry biomolecules, various EV-based therapeutic applications have been devised for several pathological conditions, including eye diseases. In the eye, EVs have been detected in the retina, aqueous humor, vitreous body and also in tears. Experiences with other forms of intraocular drug applications have opened new ways to use EVs in the treatment of retinal diseases. We here provide a comprehensive summary of the main in vitro, in vivo, and ex vivo literature-based studies on EVs' role in ocular physiological and pathological conditions. We have focused on age-related macular degeneration, diabetic retinopathy, glaucoma, which are common eye diseases leading to permanent blindness, if not treated properly. In addition, the putative use of EVs in retinitis pigmentosa and other retinopathies is discussed. Finally, we have reviewed the potential of EVs as therapeutic tools and/or biomarkers in the above-mentioned retinal disorders. Evidence emerging from experimental disease models and human material strongly suggests future diagnostic and/or therapeutic exploitation of these biological agents in various ocular disorders with a good possibility to improve the patient's quality of life.},
}
@article {pmid38011512,
year = {2023},
author = {Deng, C and Li, M and Liu, Y and Yan, C and He, Z and Chen, ZY and Zhu, H},
title = {Cholesterol Oxidation Products: Potential Adverse Effect and Prevention of Their Production in Foods.},
journal = {Journal of agricultural and food chemistry},
volume = {71},
number = {48},
pages = {18645-18659},
doi = {10.1021/acs.jafc.3c05158},
pmid = {38011512},
issn = {1520-5118},
mesh = {Humans ; Oxidation-Reduction ; *Cholesterol/metabolism ; *Food ; Antioxidants/metabolism ; Food Handling ; Polyphenols ; },
abstract = {Cholesterol oxidation products (COPs) are a group of substances formed during food processing. COPs in diet is a health concern because they may affect human health in association with the risk of various diseases including atherosclerosis, Alzheimer's disease, age-related macular degeneration, diabetes, and chronic gastrointestinal inflammatory colitis. Production of COPs in foods can be affected by many factors such as temperature, pH, light, oxygen, water, carbohydrates, fatty acids, proteins, and metal cations. The key issue is preventing its generation in foods. Some COPs can also be produced in vivo by both nonenzymatic and enzymatic-catalyzed oxidation reactions. Currently, a number of natural antioxidants such as catechins, flavonoids, and other polyphenols have been proven to inhibit the generation of COPs. In addition, measures taken during food processing can also minimize the production of COPs, such as the Maillard reaction and marinating food with plant polyphenol-rich seasonings. In conclusion, a comprehensive approach encompassing the suppression on COPs generation and implementation of processing measures is imperative to safeguard human health against the production of COPs in the food chain.},
}
@article {pmid38009288,
year = {2023},
author = {Casanovas-Marsal, JO and Viladés Palomar, E and Bartol-Puyal, FA and Hernández Vian, R and Pablo Júlvez, LE},
title = {[Relationship between treatment and cost with visual acuity improvement in age-related macular degeneration].},
journal = {Anales del sistema sanitario de Navarra},
volume = {46},
number = {3},
pages = {},
pmid = {38009288},
issn = {2340-3527},
mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; Male ; *Ranibizumab/adverse effects ; Angiogenesis Inhibitors/therapeutic use/adverse effects ; Retrospective Studies ; *Macular Degeneration/drug therapy/chemically induced ; Visual Acuity ; Treatment Outcome ; Follow-Up Studies ; },
abstract = {BACKGROUND: We examined the relationship between visual acuity changes (VA) and the cost of care and treatment with anti-vascular endothelial growth factors (antiVEGF) in patients diagnosed with age-related exudative macular degeneration (exudative AMD).<br><br>METHODS: Observational, longitudinal, retrospective study of patients &#x2265;50 years of age diagnosed with exudative AMD, with a log-MAR VA between 0.6 and 0.06. and 0.06. Follow-up and treatment were done in our tertiary hospital between January 1, 2014 and December 31, 2018.<br><br>RESULTS: The study included 778 patients; 62.2% female and mean age 79.83&#xb1;7.94 years; 957 eyes had exudative AMD. Mean of final VA (0.65&#xb1;0.45) increasing 3.2% compared to initial values. Ranibizumab was administered to 60.3% of the eyes, aflibercept to 10.2% and ranibizumab + aflibercept (mixed group) to 29.5%. Significant increase in VA was seen in the group with the mixed treatment, with no inter-group differences. Although follow-up/treatment was longer for the mixed group, they received fewer anti-VEGF injections and optical coherence tomography (OCT). The total expenditure per year and treated eye was &#x20ac; 1,972.7&#xb1;824.5; costs were higher for visit, OCT, and treatment in the aflibercept group, and lower for fluorescein angiography, antiVEGF treatment, and total costs in the mixed group. Decimal VA gain had a cost of &#x20ac; 872&#xb1;1,077.7 with no significant inter-group differences.<br><br>CONCLUSIONS: AntiVEGF treatments (ranibizumab, aflibercept, or both) maintained VA in patients with exudative AMD. Overall, care and treatment costs were lower in the group that received both drugs.},
}
@article {pmid38008405,
year = {2024},
author = {Garg, A and Nanji, K and Tai, F and Phillips, M and Zeraatkar, D and Garg, SJ and Sadda, SR and Kaiser, PK and Guymer, RH and Sivaprasad, S and Wykoff, CC and Chaudhary, V},
title = {The effect of complement C3 or C5 inhibition on geographic atrophy secondary to age-related macular degeneration: A living systematic review and meta-analysis.},
journal = {Survey of ophthalmology},
volume = {69},
number = {3},
pages = {349-361},
doi = {10.1016/j.survophthal.2023.11.008},
pmid = {38008405},
issn = {1879-3304},
mesh = {Humans ; *Complement C3/metabolism/antagonists &amp; inhibitors ; *Complement C5/antagonists &amp; inhibitors ; *Complement Inactivating Agents/therapeutic use ; *Geographic Atrophy/drug therapy/diagnosis/etiology/physiopathology ; Macular Degeneration/drug therapy ; Visual Acuity ; },
abstract = {With the introduction of therapies to treat geographic atrophy (GA), GA management in clinical practice is now possible. A living systematic review can provide access to timely and robust evidence synthesis. This review found that complement factor 3 and 5 (C3 and C5) inhibition compared to sham likely reduces change in square root GA area at 12 months and untransformed GA area at 24 months. There is likely little to no difference in the rate of systemic treatment-emergent adverse events compared to sham. C3 and C5 inhibition, however, likely does not improve best-corrected visual acuity (BCVA) at 12 months, and the evidence is uncertain regarding change in BCVA at 24 months. Higher rates of ocular treatment emergent adverse effects with complement inhibition occur at 12 months and likely at 24 months. Complement inhibition likely results in new onset neovascular age-related macular degeneration at 12 months. This living meta-analysis will continuously incorporate new evidence.},
}
@article {pmid38008231,
year = {2024},
author = {Zhi, X and Lu, H and Ma, D and Liu, J and Luo, L and Wang, L and Qin, Y},
title = {Melatonin protects photoreceptor cells against ferroptosis in dry AMD disorder by inhibiting GSK-3B/Fyn-dependent Nrf2 nuclear translocation.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1870},
number = {2},
pages = {166969},
doi = {10.1016/j.bbadis.2023.166969},
pmid = {38008231},
issn = {1879-260X},
mesh = {Mice ; Animals ; *Melatonin/pharmacology ; NF-E2-Related Factor 2/genetics/metabolism ; Glycogen Synthase Kinase 3 beta/genetics ; *Ferroptosis ; Mice, Inbred C57BL ; Photoreceptor Cells/metabolism ; Iron/pharmacology ; },
abstract = {BACKGROUND: Ferroptosis is a type of non-apoptotic cell death that relies on iron ions and reactive oxygen species to induce lipid peroxidation. This study aimed to determine whether ferroptosis exists in the pathogenesis of dry age-related macular degeneration (AMD) and to confirm that melatonin (MLT) suppresses the photoreceptor cell ferroptosis signaling pathway.<br><br>METHODS: We exposed 661W cells to sodium iodate (NaIO3) in vitro and treated them with different concentrations of MLT. In vivo, C57BL/6 mice were given a single caudal vein injection of NaIO3, followed by an intraperitoneal injection of MLT, and eyeballs were taken for subsequent trials.<br><br>RESULTS: We found that NaIO3 could induce photoreceptor cell death and lipid peroxide accumulation, and result in changes in the expression of ferroptosis-related factors and iron maintenance proteins, which were treated by MLT. We further demonstrated that MLT can block Fyn-dependent Nrf2 nuclear translocation by suppressing the GSK-3&#x3b2; signaling pathway. In addition, the therapeutic effect of MLT was significantly inhibited when Nrf2 was silenced.<br><br>CONCLUSIONS: Our findings provide a novel insight that NaIO3 induces photoreceptor cell ferroptosis in dry AMD and suggest that MLT has therapeutic effects by suppressing GSK-3&#x3b2;/Fyn-dependent Nrf2 nuclear translocation.},
}
@article {pmid38008218,
year = {2024},
author = {Chandra, RS and Ying, GS},
title = {Predicting Visual Acuity Responses to Anti-VEGF Treatment in the Comparison of Age-related Macular Degeneration Treatments Trials Using Machine Learning.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {5},
pages = {419-430},
pmid = {38008218},
issn = {2468-6530},
support = {U10 EY017825/EY/NEI NIH HHS/United States ; U10 EY017826/EY/NEI NIH HHS/United States ; U10 EY017828/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; U10 EY017823/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Visual Acuity ; *Machine Learning ; *Angiogenesis Inhibitors/administration &amp; dosage ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Male ; *Intravitreal Injections ; Female ; *Ranibizumab/administration &amp; dosage ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; Bevacizumab/administration &amp; dosage ; Treatment Outcome ; ROC Curve ; Aged, 80 and over ; },
abstract = {PURPOSE: To evaluate multiple machine learning (ML) models for predicting 2-year visual acuity (VA) responses to anti-vascular endothelial growth factor (anti-VEGF) treatment in the Comparison of Age-related Macular Degeneration (AMD) Treatments Trials (CATT) for patients with neovascular AMD (nAMD).<br><br>DESIGN: Secondary analysis of public data from a randomized clinical trial.<br><br>PARTICIPANTS: A total of 1029 CATT participants who completed 2 years of follow-up with untreated active nAMD and baseline VA between 20/25 and 20/320 in the study eye.<br><br>METHODS: Five ML models (support vector machine, random forest, extreme gradient boosting, multilayer perceptron neural network, and lasso) were applied to clinical and image data from baseline and weeks 4, 8, and 12 for predicting 4 VA outcomes (&#x2265; 15-letter VA gain, &#x2265; 15-letter VA loss, VA change from baseline, and actual VA) at 2 years. The CATT data from 1029 participants were randomly split for training (n&#xa0;= 717), from which the models were trained using 10-fold cross-validation, and for final validation on a test data set (n&#xa0;= 312).<br><br>MAIN OUTCOME MEASURES: Performances of ML models were assessed by R[2] and mean absolute error (MAE) for predicting VA change from baseline and actual VA at 2 years, by the area under the receiver operating characteristic curve (AUC) for predicting &#x2265; 15-letter VA gain and loss from baseline.<br><br>RESULTS: Using training data up to week 12, the ML models from cross-validation achieved mean R[2] of 0.24 to 0.29 (MAE&#xa0;= 9.1-9.8 letters) for predicting VA change and 0.37 to 0.41 (MAE&#xa0;= 9.3-10.2 letters) for predicting actual VA at 2 years. The mean AUCs for predicting &#x2265; 15-letter VA gain and loss at 2 years was 0.84 to 0.85 and 0.58 to 0.73, respectively. In final validation on the test data set up to week 12, the models had an R[2] of 0.33 to 0.38 (MAE&#xa0;= 8.9-9.9 letters) for predicting VA change, an R[2] of 0.37 to 0.45 (MAE&#xa0;= 8.8-10.2 letters) for predicting actual VA at 2 years, and AUCs of 0.85 to 0.87 and 0.67 to 0.79 for predicting &#x2265; 15-letter VA gain and loss, respectively.<br><br>CONCLUSIONS: Machine learning models have the potential to predict 2-year VA response to anti-VEGF treatment using clinical and imaging features from the loading dose phase, which can aid in decision-making around treatment protocols for patients with nAMD.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid38007487,
year = {2023},
author = {Chang, YH and Hsing, CH and Chiu, CJ and Wu, YR and Hsu, SM and Hsu, YH},
title = {Protective role of IL-17-producing γδ T cells in a laser-induced choroidal neovascularization mouse model.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
pages = {279},
pmid = {38007487},
issn = {1742-2094},
support = {MOST-111-2314-B-384-010-MY2//Ministry of Science and Technology, Taiwan/ ; MOST-111-2628-B-006-018//Ministry of Science and Technology, Taiwan/ ; },
mesh = {Aged ; Animals ; Humans ; Mice ; *Choroidal Neovascularization/metabolism ; Disease Models, Animal ; Eye/metabolism ; Interleukin-17/metabolism ; Lasers ; *Macular Degeneration/etiology/metabolism ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Vision loss in patients with wet/exudative age-related macular degeneration (AMD) is associated with choroidal neovascularization (CNV), and AMD is the leading cause of irreversible vision impairment in older adults. Interleukin-17A (IL-17A) is a component of the microenvironment associated with some autoimmune diseases. Previous studies have indicated that wet AMD patients have elevated serum IL-17A levels. However, the effect of IL-17A on AMD progression needs to be better understood. We aimed to investigate the role of IL-17A in a laser-induced CNV mouse model.<br><br>METHODS: We established a laser-induced CNV mouse model in wild-type (WT) and IL-17A-deficient mice and then evaluated the disease severity of these mice by using fluorescence angiography. We performed enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS) to analyze the levels of IL-17A and to investigate the immune cell populations in the eyes of WT and IL-17A-deficient mice. We used ARPE-19 cells to clarify the effect of IL-17A under oxidative stress.<br><br>RESULTS: In the laser-induced CNV model, the CNV lesions were larger in IL-17A-deficient mice than in WT mice. The numbers of &#x3b3;&#x3b4; T cells, CD3[+]CD4[+]ROR&#x3b3;t[+] T cells, Treg cells, and neutrophils were decreased and the number of macrophages was increased in the eyes of IL-17A-deficient mice compared with WT mice. In WT mice, IL-17A-producing &#x3b3;&#x3b4; T-cell numbers increased in a time-dependent manner from day 7 to 28 after laser injury. IL-6 levels increased and IL-10, IL-24, IL-17F, and GM-CSF levels decreased in the eyes of IL-17A-deficient mice after laser injury. In vitro, IL-17A inhibited apoptosis and induced the expression of the antioxidant protein HO-1 in ARPE-19 cells under oxidative stress conditions. IL-17A facilitated the repair of oxidative stress-induced barrier dysfunction in ARPE-19 cells.<br><br>CONCLUSIONS: Our findings provide new insight into the protective effect of IL-17A in a laser-induced CNV model and reveal a novel regulatory role of IL-17A-producing &#x3b3;&#x3b4; T cells in the ocular microenvironment in wet AMD.},
}
@article {pmid38007475,
year = {2023},
author = {Roshanshad, A and Roshanshad, R and Moosavi, SA and Ardekani, A and Nabavizadeh, SS and Fereidooni, R and Ashraf, H and Vardanjani, HM},
title = {Prevalence of age-related macular degeneration in Iran and its projections through 2050: a systematic review and meta-analysis.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {484},
pmid = {38007475},
issn = {1471-2415},
mesh = {Male ; Female ; Humans ; Iran/epidemiology ; Prevalence ; Cross-Sectional Studies ; *Macular Degeneration/epidemiology ; Blindness/etiology ; },
abstract = {BACKGROUND: Age-related Macular Degeneration (AMD) is one of the most common causes of vision loss. A substantial increase in the burden of AMD is expected in the aging populations, including the Iranians. We investigated the age and gender-specific prevalence of AMD and its determinants in Iran.<br><br>METHODS: We systematically searched international (PubMed, Scopus, Embase, etc.) and local (IranDoc, Magiran, etc.) online databases. We included cross-sectional or cohort studies, either clinic- or population-based, published on the prevalence of AMD among Iranians, with no limitation on age. Joanna Briggs Institute (JBI) tools for critical appraisal were used. Prevalence estimates are pooled by applying random-effects modeling. Subgroup analysis and meta-regression were performed.<br><br>RESULTS: Seventeen studies with 16,120 participants were included. Based on studies in general population, the pooled prevalence of AMD was 10.8% (95% CI: 6.5-16.2%) in males, and 9.8% (95% CI: 4.7-16.4%) in females. 8.5% of moderate vision impaired, 13.6% of severe vision impaired, and 15.7% of blind participants were affected by AMD. The prevalence of AMD was 2% in 40-49, and 32.3% in the &#x2265;&#x2009;80 population. The prevalence of AMD was 11.9% among the visually impaired vs. 8.7% in the general population. The study's sampling method, location, and mean age were correlated with the heterogeneities of the prevalence. We observed an increasing trend in the number of AMD cases (average annual percent change&#x2009;=&#x2009;3.66%; 95% CI: 3.65-3.67%) from 1990 to 2050. The expected number of AMD cases in Iran will be near 5.5&#xa0;million by 2050.<br><br>CONCLUSION: The prevalence of AMD in Iran was somewhere between the prevalence of Asians and Europeans. Given the aging trend of the Iranian community and an average annual percent change of 3.66%, it is indispensable to adopt preventive and screening policies to diminish the burden of the disease in the future decades.},
}
@article {pmid38004855,
year = {2023},
author = {Yan, C and Liu, M and Shi, G and Fan, J and Li, Y and Wu, S and Hu, J},
title = {Design of a Subretinal Injection Robot Based on the RCM Mechanism.},
journal = {Micromachines},
volume = {14},
number = {11},
pages = {},
pmid = {38004855},
issn = {2072-666X},
support = {YSBR-067.//CAS Project for Young Scientists in Basic Research,/ ; },
abstract = {This study presents an investigation focusing on the advancement of a robot designed for subretinal injections in the context of macular degeneration treatment. The technique of subretinal injection surgery stands as the most efficacious approach for the successful transplantation of stem cells into the retinal pigment epithelium layer. This particular procedure holds immense significance in advancing research and implementing therapeutic strategies involving retinal stem cell transplantation. The execution of artificial subretinal surgery poses considerable challenges which can be effectively addressed through the utilization of subretinal injection surgery robots. The development process involved a comprehensive modeling phase, integrating computer-aided design (CAD) and finite element analysis (FEA) techniques. These simulations facilitated iterative enhancements of the mechanical aspects pertaining to the robotic arm. Furthermore, MATLAB was employed to simulate and visualize the robot's workspace, and independent verification was conducted to ascertain the range of motion for each degree of freedom.},
}
@article {pmid38004569,
year = {2023},
author = {Pariente, A and Peláez, R and Ochoa, R and Pérez-Sala, &#xc1; and Villanueva-Martínez, &#xc1; and Bobadilla, M and Larráyoz, IM},
title = {Targeting 7KCh-Induced Cell Death Response Mediated by p38, P2X7 and GSDME in Retinal Pigment Epithelium Cells with Sterculic Acid.},
journal = {Pharmaceutics},
volume = {15},
number = {11},
pages = {},
pmid = {38004569},
issn = {1999-4923},
support = {PI19/01805//Instituto de Salud Carlos III/ ; CPII20/00029//Instituto de Salud Carlos III/ ; RTC2019-007399-1//Ministerio de Ciencia e Innovaci&#xf3;n/ ; },
abstract = {Age-related macular degeneration (AMD) is the main cause of blindness in developed countries. AMD is characterized by the formation of drusen, which are lipidic deposits, between retinal pigment epithelium (RPE) and the choroid. One of the main molecules accumulated in drusen is 7-Ketocholesterol (7KCh), an oxidized-cholesterol derivative. It is known that 7KCh induces inflammatory and cytotoxic responses in different cell types and the study of its mechanism of action is interesting in order to understand the development of AMD. Sterculic acid (SA) counteracts 7KCh response in RPE cells and could represent an alternative to improve currently used AMD treatments, which are not efficient enough. In the present study, we determine that 7KCh induces a complex cell death signaling characterized by the activation of necrosis and an alternative pyroptosis mediated by P2X7, p38 and GSDME, a new mechanism not yet related to the response to 7KCh until now. On the other hand, SA treatment can successfully attenuate the activation of both necrosis and pyroptosis, highlighting its therapeutic potential for the treatment of AMD.},
}
@article {pmid38004422,
year = {2023},
author = {Latifi-Navid, H and Barzegar Behrooz, A and Jamehdor, S and Davari, M and Latifinavid, M and Zolfaghari, N and Piroozmand, S and Taghizadeh, S and Bourbour, M and Shemshaki, G and Latifi-Navid, S and Arab, SS and Soheili, ZS and Ahmadieh, H and Sheibani, N},
title = {Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {11},
pages = {},
pmid = {38004422},
issn = {1424-8247},
support = {P30 EY016665/EY/NEI NIH HHS/United States ; P30EY016665/EY/NEI NIH HHS/United States ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual impairment in the elderly. The current management of nAMD is limited and involves regular intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF). However, the effectiveness of these treatments is limited by overlapping and compensatory pathways leading to unresponsiveness to anti-VEGF treatments in a significant portion of nAMD patients. Therefore, a system view of pathways involved in pathophysiology of nAMD will have significant clinical value. The aim of this study was to identify proteins, miRNAs, long non-coding RNAs (lncRNAs), various metabolites, and single-nucleotide polymorphisms (SNPs) with a significant role in the pathogenesis of nAMD. To accomplish this goal, we conducted a multi-layer network analysis, which identified 30 key genes, six miRNAs, and four lncRNAs. We also found three key metabolites that are common with AMD, Alzheimer's disease (AD) and schizophrenia. Moreover, we identified nine key SNPs and their related genes that are common among AMD, AD, schizophrenia, multiple sclerosis (MS), and Parkinson's disease (PD). Thus, our findings suggest that there exists a connection between nAMD and the aforementioned neurodegenerative disorders. In addition, our study also demonstrates the effectiveness of using artificial intelligence, specifically the LSTM network, a fuzzy logic model, and genetic algorithms, to identify important metabolites in complex metabolic pathways to open new avenues for the design and/or repurposing of drugs for nAMD treatment.},
}
@article {pmid38003923,
year = {2023},
author = {Perrault, MA and Lauer, G and Voss, S and Seitz, B and Käsmann-Kellner, B},
title = {Visual Impairment and Low Vision Aids-A Comparison between Children and Adults.},
journal = {Journal of personalized medicine},
volume = {13},
number = {11},
pages = {},
pmid = {38003923},
issn = {2075-4426},
abstract = {(1) Background: This study aims to highlight differences in the etiology and fitting of low vision aids in visually impaired children and adolescents in comparison to adults. (2) Methods: A retrospective data collection from visually impaired patients presenting to obtain assistive devices from 1 January 2016 to 30 April 2020 was conducted. A total of 502 patients were included. Inclusion criteria were a minimum age of 4 years and the chart notation of a best-corrected distance visual acuity in the patient record prior to the fitting of magnifying visual aids. (3) Results: Of the 502 patients, 147 (29.3%) were children under the age of 18 years. The most common cause of visual impairment in children was albinism, and in adults, it was age-related macular degeneration (AMD). Children showed better distance visual acuity, with a median of 0.88 logMAR (Logarithm of the Minimum Angle of Resolution) compared to 1.0 in adults (p = 0.001). Near visual acuity was also significantly better, with a median of 0.54 logMAR in children compared to 0.9 in adults (p < 0.001). Near and distance visual acuity were significantly improved by fitting magnifying visual aids (p < 0.001). After fitting, near visual acuity averaged 0.3 logMAR, and distance visual acuity, 0.7. The most commonly prescribed aids were optical vision aids, which 68.5% of the patients received; 43.8% received electronic aids. In children, optical aids were more frequently prescribed, and in adults, electronic and acoustic aids (p < 0.001). (4) Conclusion: Visually impaired patients can regain the ability to read and improve distance vision by using individually adapted and tested magnifying vision aids, often with optical aids alone. Differences between children and adults could be discovered in the etiology and severity of visual impairment, as well as in the provision type of low vision aids.},
}
@article {pmid38003595,
year = {2023},
author = {Koller, A and Lamina, C and Brandl, C and Zimmermann, ME and Stark, KJ and Weissensteiner, H and Würzner, R and Heid, IM and Kronenberg, F},
title = {Systemic Evidence for Mitochondrial Dysfunction in Age-Related Macular Degeneration as Revealed by mtDNA Copy Number Measurements in Peripheral Blood.},
journal = {International journal of molecular sciences},
volume = {24},
number = {22},
pages = {},
pmid = {38003595},
issn = {1422-0067},
support = {W-1253 DK HOROS//FWF Austrian Science Fund/ ; BMBF 01ER1206, BMBF 01ER1507//German Federal Ministry of Education and Research/ ; HE 3690/5-1 and HE 3690/7-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; Aged ; *DNA, Mitochondrial/genetics ; DNA Copy Number Variations ; Mitochondria/genetics ; *Macular Degeneration/genetics ; Retina ; },
abstract = {Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm in the retinal tissue. However, it is unclear whether the effects are locally restricted to the high-energy-demanding retinal pigment epithelium or are also systematically present. Therefore, we measured mtDNA copy number (mtDNA-CN) in peripheral blood using a qPCR approach with plasmid normalization in elderly participants with and without AMD from the AugUR study (n = 2262). We found significantly lower mtDNA-CN in the blood of participants with early (n = 453) and late (n = 170) AMD compared to AMD-free participants (n = 1630). In regression analyses, we found lower mtDNA-CN to be associated with late AMD when compared with AMD-free participants. Each reduction of mtDNA-CN by one standard deviation increased the risk for late AMD by 24%. This association was most pronounced in geographic atrophy (OR = 1.76, 95% CI 1.19-2.60, p = 0.004), which has limited treatment options. These findings provide new insights into the relationship between mtDNA-CN in blood and AMD, suggesting that it may serve as a more accessible biomarker than mtDNA-CN in the retina.},
}
@article {pmid38002079,
year = {2023},
author = {Kozhevnikova, OS and Fursova, AZ and Derbeneva, AS and Nikulich, IF and Devyatkin, VA and Kolosova, NG},
title = {Pharmacogenetic Association between Allelic Variants of the Autophagy-Related Genes and Anti-Vascular Endothelial Growth Factor Treatment Response in Neovascular Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {11},
number = {11},
pages = {},
pmid = {38002079},
issn = {2227-9059},
support = {21-15-00047//Russian Science Foundation/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of late-onset blindness in elderly. The occurrence and development of AMD is a multifactorial complex process where autophagy plays an important role. The first-line drugs for neovascular AMD (nAMD) are inhibitors of VEGF, with up to 30% of patients having an incomplete response to treatment. Genetic factors may influence the response to anti-VEGF therapy and explain treatment outcome variability. We aimed to estimate the role of polymorphic markers of the MTOR (rs1064261, rs1057079, rs11121704, rs2295080), SQSTM1 (rs10277), ULK1 (rs11246867, rs3088051), MAP1LC3A (rs73105013) and ATG5 (rs573775) genes in the development of nAMD and the efficacy of anti-VEGF therapy response.<br><br>METHODS: Genotyping by allele-specific PCR was performed in 317 controls and 315 nAMD patients in the Russian population. Of them, 196 treatment-naive nAMD patients underwent three monthly intravitreal injections (IVIs) of aflibercept. Genotypic frequencies were compared with OCT markers of therapy effectiveness and best-corrected visual acuity (BCVA) measures. The main outcomes were the BCVA gain and decrease in central retinal thickness (CRT).<br><br>RESULTS: MTOR-rs1057079-C, MTOR-rs11121704-C and MTOR-rs2295080-G alleles were associated with an increased risk of nAMD. The BCVA was increased in 117 (59.7%) patients by 10 [5-20] letters, did not changed in 59 (30.1%), and was decreased in 20 (10.2%) patients. ULK1-rs3088051 was associated with BCVA change. Among patients with the TT and CT genotypes for ULK1-rs3088051, an improvement in visual acuity was noted in 67.6% and 53.8% of cases, while in patients with the CC genotype, an increase in BCVA was recorded in 37.5% of cases (p = 0.01). The decrease in CRT was associated with SQSTM1-rs10277 (p = 0.001): it was significantly higher in TT (93 [58-122] mkm) and CT (66 [30-105] mkm) carriers compared to the CC genotype (47 [24-68] mkm). Other SNPs did not show significant associations with the outcome of anti-VEGF treatment.<br><br>CONCLUSIONS: MTOR gene polymorphisms are moderately associated with the risk of nAMD. SQSTM1-rs10277 and ULK1-rs3088051 may influence short-term response to intravitreal anti-VEGF treatment. The results suggest that autophagy could be a target for future drugs to overcome resistance to anti-VEGF therapy.},
}
@article {pmid38002042,
year = {2023},
author = {Choubey, M and Tirumalasetty, MB and Bora, NS and Bora, PS},
title = {Linking Adiponectin and Its Receptors to Age-Related Macular Degeneration (AMD).},
journal = {Biomedicines},
volume = {11},
number = {11},
pages = {},
pmid = {38002042},
issn = {2227-9059},
abstract = {In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN's multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue's profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging.},
}
@article {pmid38001960,
year = {2023},
author = {Amankwa, CE and Kodati, B and Donkor, N and Acharya, S},
title = {Therapeutic Potential of Antioxidants and Hybrid TEMPOL Derivatives in Ocular Neurodegenerative Diseases: A Glimpse into the Future.},
journal = {Biomedicines},
volume = {11},
number = {11},
pages = {},
pmid = {38001960},
issn = {2227-9059},
support = {R01 EY029823/EY/NEI NIH HHS/United States ; R01EY029823/EY/NEI NIH HHS/United States ; },
abstract = {Reactive oxygen species play a significant role in the pathogenesis of various ocular neurodegenerative diseases especially glaucoma, age-related macular degeneration (AMD), and ocular ischemic stroke. Increased oxidative stress and the accumulation of ROS have been implicated in the progression of these diseases. As a result, there has been growing interest in exploring potential therapeutic and prophylactic strategies involving exogenous antioxidants. In recent years, there have been significant advancements in the development of synthetic therapeutic antioxidants for targeting reactive oxygen species (ROS) in neurodegenerative diseases. One area of focus has been the development of hybrid TEMPOL derivatives. In the context of ocular diseases, the application of next-generation hybrid TEMPOL antioxidants may offer new avenues for neuroprotection. By targeting ROS and reducing oxidative stress in the retina and optic nerve, these compounds have the potential to preserve retinal ganglion cells and trabecular meshwork and protect against optic nerve damage, mitigating irreversible blindness associated with these diseases. This review seeks to highlight the potential impact of hybrid TEMPOL antioxidants and their derivatives on ocular neurodegenerative disorders.},
}
@article {pmid38001832,
year = {2023},
author = {Niu, Y and Xi, Y and Jing, Y and Zhou, Z and Sun, X and Zhang, G and Yuan, T and Chang, T and Dou, G},
title = {Endothelial Notch Signaling Regulates the Function of the Retinal Pigment Epithelial Barrier via EC Angiocrine Signaling.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {11},
pages = {},
pmid = {38001832},
issn = {2076-3921},
support = {81970814, 81670863, 82000905//National Natural Science Foundation of China/ ; 2021JSTS28//clinical AFFMU foundation support/ ; },
abstract = {The outer blood-retina barrier (oBRB), comprises tightly connected retinal pigment epithelium (RPE) cells, Bruch's membrane, and choroid blood vessels, and is essential for retinal health and normal visual function. Disruption of the RPE barrier and its dysfunction can lead to retinal disorders such as age-related macular degeneration (AMD). In the present study, we investigated the essential role of choroid endothelial cells (ECs) in the RPE barrier formation process and its dysfunction. We discovered that ECs promoted RPE barrier formation through angiocrine signaling. Through blocking or activating endothelial Notch signaling and conducting experiments in vitro and in vivo, we confirmed that endothelial Notch signaling regulated the expression of heparin-binding epidermal growth factor (HBEGF) and consequently impacted the expression and activity of matrix metalloproteinases (MMP)-9 in RPE cells. This modulation influenced the RPE extracellular matrix deposition, tight junctions and RPE barrier function. In in vivo experiments, the intravitreal administration of recombinant HBEGF (r-HBEGF) alleviated the RPE barrier disruption induced by subretinal injection (SI) or laser treatment and also rescued RPE barrier disruption in endothelial Notch-deficient mice. Our results showed that the endothelial Notch signaling drove HBEGF expression through angiocrine signaling and effectively improved RPE barrier function by regulating the MMP-9 expression in RPE cells. It suggests that the modulation of Notch signaling in the choroidal endothelium may offer a novel therapeutic strategy for retinal degenerative diseases.},
}
@article {pmid38000700,
year = {2024},
author = {Jabbehdari, S and Oganov, AC and Rezagholi, F and Mohammadi, S and Harandi, H and Yazdanpanah, G and Arevalo, JF},
title = {Age-related macular degeneration and neurodegenerative disorders: Shared pathways in complex interactions.},
journal = {Survey of ophthalmology},
volume = {69},
number = {3},
pages = {303-310},
doi = {10.1016/j.survophthal.2023.11.003},
pmid = {38000700},
issn = {1879-3304},
mesh = {Humans ; *Macular Degeneration/metabolism ; *Neurodegenerative Diseases/metabolism ; *Oxidative Stress/physiology ; Autophagy/physiology ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly, and neurodegenerative disorders such as Alzheimer disease and Parkinson disease are debilitating conditions that affect millions worldwide. Despite the different clinical manifestations of these diseases, growing evidence suggests that they share common pathways in their pathogenesis including inflammation, oxidative stress, and impaired autophagy. In this review, we explore the complex interactions between AMD and neurodegenerative disorders, focusing on their shared mechanisms and potential therapeutic targets. We also discuss the current opportunities and challenges for developing effective treatments that can target these pathways to prevent or slow down disease progression in AMD. Some of the promising strategies that we explore include modulating the immune response, reducing oxidative stress, enhancing autophagy and lysosomal function, and targeting specific protein aggregates or pathways. Ultimately, a better understanding of the shared pathways between AMD and neurodegenerative disorders may pave the way for novel and more efficacious treatments.},
}
@article {pmid37998544,
year = {2023},
author = {Tun, YZ and Aimmanee, P},
title = {A Complete Review of Automatic Detection, Segmentation, and Quantification of Neovascularization in Optical Coherence Tomography Angiography Images.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {22},
pages = {},
pmid = {37998544},
issn = {2075-4418},
support = {NRCT5-RSA63010-05//National Research Council of Thailand/ ; },
abstract = {Optical coherence tomography (OCT) is revolutionizing the way we assess eye complications such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). With its ability to provide layer-by-layer information on the retina, OCT enables the early detection of abnormalities emerging underneath the retinal surface. The latest advancement in this field, OCT angiography (OCTA), takes this to the next level by providing detailed vascular information without requiring dye injections. One of the most significant indicators of DR and AMD is neovascularization, the abnormal growth of unhealthy vessels. In this work, the techniques and algorithms used for the automatic detection, classification, and segmentation of neovascularization in OCTA images are explored. From image processing to machine learning and deep learning, works related to automated image analysis of neovascularization are summarized from different points of view. The problems and future work of each method are also discussed.},
}
@article {pmid37996905,
year = {2023},
author = {Ramirez, KA and Drew-Bear, LE and Vega-Garces, M and Betancourt-Belandria, H and Arevalo, JF},
title = {An update on visual prosthesis.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {73},
pmid = {37996905},
issn = {2056-9920},
abstract = {PURPOSE: To review the available evidence on the different retinal and visual prostheses for patients with retinitis pigmentosa and new implants for other indications including dry age-related macular degeneration.<br><br>METHODS: The PubMed, GoogleScholar, ScienceDirect, and ClinicalTrials databases were the main resources used to conduct the medical literature search. An extensive search was performed to identify relevant articles concerning the worldwide advances in retinal prosthesis, clinical trials, status of devices and potential future directions up to December 2022.<br><br>RESULTS: Thirteen devices were found to be current and were ordered by stimulation location. Six have active clinical trials. Four have been discontinued, including the Alpha IMS, Alpha AMS, IRIS II, and ARGUS II which had FDA and CE mark approval. Future directions will be presented in the review.<br><br>CONCLUSION: This review provides an update of retinal prosthetic devices, both current and discontinued. While some devices have achieved visual perception in animals and/or humans, the main issues impeding the commercialization of these devices include: increased length of time to observe outcomes, difficulties in finding validated meaures for use in studies, unknown long-term effects, lack of funding, and a low amount of patients simultaneously diagnosed with RP lacking other comorbid conditions. The ARGUS II did get FDA and CE mark approval so it was deemed safe and also effective. However, the company became more focused on a visual cortical implant. Future efforts are headed towards more biocompatible, safe, and efficacious devices.},
}
@article {pmid37995057,
year = {2023},
author = {Bodaghi, B and Khanani, AM and Khoramnia, R and Pavesio, C and Nguyen, QD},
title = {Gains in the current understanding of managing neovascular AMD with brolucizumab.},
journal = {Journal of ophthalmic inflammation and infection},
volume = {13},
number = {1},
pages = {51},
pmid = {37995057},
issn = {1869-5760},
abstract = {BACKGROUND: Unresolved retinal fluid and high injection burden are major challenges for patients with neovascular age-related macular degeneration. Brolucizumab addresses these challenges by providing robust vision gains and superior fluid resolution, with the potential for longer treatment intervals. Brolucizumab has been associated with adverse events of retinal vasculitis and retinal vascular occlusion typically in the presence of intraocular inflammation (IOI). To define the incidence of the adverse events, Novartis convened an external safety review committee, which found a rate of 4.6% for definite or probable IOI, 3.3% for retinal vasculitis, and 2.1% for retinal vascular occlusion in the HAWK and HARRIER trials. Novartis also established a coalition to explore 4 areas regarding the adverse events: root cause, patient characterization, event mitigation and vigilance, and treatment protocols for the adverse events. Based on the coalition findings, a risk mitigation framework was developed. Prior to initiating treatment with brolucizumab, it is important to weigh the potential benefit against risk of adverse events and to consider patient risk factors such as prior history of IOI and/or retinal vascular occlusion. To mitigate the potential for IOI-related adverse events, it is important to conduct a thorough dilated eye examination before each injection and closely monitor patients throughout treatment. Patients should be educated on symptoms of IOI to monitor for. Brolucizumab should not be injected in the presence of active IOI. If an adverse event is identified, prompt and intensive treatment should be considered.<br><br>CONCLUSION: Progress has been made in understanding how to mitigate IOI-related adverse events following treatment&#xa0;with brolucizumab.},
}
@article {pmid37995014,
year = {2024},
author = {Huang, CH and Lai, TT and Yang, CH and Hsieh, YT},
title = {Two-Year Real-World Results for Aflibercept Using the Treat-and-Extend Regimen in Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {1},
pages = {385-396},
pmid = {37995014},
issn = {2193-8245},
abstract = {INTRODUCTION: To evaluate the real-world efficacy of aflibercept using the treat-and-extend (TnE) regimen in treating neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), and to analyze biomarkers using optical coherence tomography (OCT) to predict treatment outcomes.<br><br>METHODS: Patients diagnosed with nAMD or PCV who received an intravitreal injection of aflibercept following the TnE regimen for&#x2009;&#x2265;&#x2009;2&#xa0;years were retrospectively reviewed. Data on best-corrected visual acuity (BCVA), number of injections, treatment interval, and OCT biomarkers, including central macular thickness, presence of subretinal fluid (SRF), and serous pigmented epithelial detachment, were collected at baseline and at 3, 6, 12, 18, and 24&#xa0;months after the first injection.<br><br>RESULTS: A total of 43 patients were enrolled in this study, 24 of whom were diagnosed with nAMD and 19 with PCV. The BCVA in logMAR&#xa0;(mean&#xa0;&#xb1; standard deviation) improved from 0.75&#x2009;&#xb1;&#x2009;0.41 (baseline) to 0.60&#x2009;&#xb1;&#x2009;0.41 (P&#x2009;=&#x2009;0.002) at 3 months after treatment initiation, and further improved to 0.66&#x2009;&#xb1;&#x2009;0.46 at 24 months (P&#x2009;=&#x2009;0.137). The number of injections (mean&#xa0;&#xb1; standard deviation)&#xa0;within the 2-year treatment course was 10.95&#x2009;&#xb1;&#x2009;3.65. At month 24 of the TnE regimen, the treatment interval was extended to&#x2009;&#x2265;&#x2009;16&#xa0;weeks in 60.5% of all cases and to 78.9% of the PCV cases. After three loading injections, persistent subretinal fluid and intraretinal fluid were predictive of more frequent injections (P&#x2009;=&#x2009;0.026) and poorer visual outcomes (P&#x2009;=&#x2009;0.050), respectively.<br><br>CONCLUSION: Aflibercept combined with a TnE regimen was effective in treating nAMD and PCV in a real-world setting. The treatment interval could be extended to&#x2009;&#x2265;&#x2009;16&#xa0;weeks in 60.5% of the cases after a 2-year treatment regimen. OCT can be used to predict the treatment course and visual outcomes.},
}
@article {pmid37993580,
year = {2023},
author = {Sharma, P and Shareef, I and Kalaw, FGP and Kako, RN and Lin, A and Alex, V and Nudleman, E and Walker, EH and Borooah, S},
title = {Prevalence of peripheral retinal findings in retinal patients using ultra-widefield pseudocolor fundus imaging.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {20515},
pmid = {37993580},
issn = {2045-2322},
support = {P30 EY022589/EY/NEI NIH HHS/United States ; CD-GT-0918-0746-SE/FFB/Foundation Fighting Blindness/United States ; },
mesh = {Humans ; Cross-Sectional Studies ; Prevalence ; *Retina/diagnostic imaging ; Fundus Oculi ; *Retinal Drusen ; Fluorescein Angiography/methods ; },
abstract = {Ultra-widefield retinal imaging is increasingly used in ophthalmology and optometry practices to image patients identifying peripheral abnormalities. However, the clinical relevance of these peripheral retinal abnormalities is unclear. This cross-sectional study aims to firstly validate a new grading system, secondly, assess the prevalence of peripheral retinal abnormalities in retinal patients, and finally understand how peripheral findings may associate with retinal disease. Ultra-widefield pseudocolor fundus images were taken from the eyes of clinic patients. Demographic data and clinical diagnosis for each patient was noted. The grading system was validated using masked retinal specialists. Logistic regression identified associations between retinal disease and peripheral retinal findings. Using the grading system, inter-observer agreement was 76.1% with Cohen's Kappa coefficient 0.542 (p < 0.0001) and the test-retest agreement was 95.1% with Kappa 0.677(p < 0.0001). 971 images were included, with 625 eyes (64.4%) having peripheral abnormalities. Peripheral drusen was the most common abnormality (n = 221, 22.76%) and correlated with age-related macular degeneration (p < 0.001). Novel correlations were also identified between diabetic retinopathy and retinal pigmentation as well as pigmentary degeneration. This study provides a validated system for identifying peripheral abnormalities and adds to literature highlighting peripheral retinal associations with retinal disease which would benefit from further study.},
}
@article {pmid37992380,
year = {2023},
author = {Shams, GM and Saleh, AA and Saeed, AM and El-Damaty, SN and Abdel-Ghaffar, AO},
title = {Age-Related Macular Degeneration in Patients with Androgenetic Alopecia: Could the Monocyte/HDL Ratio Be the Link?.},
journal = {Dermatology practical &amp; conceptual},
volume = {13},
number = {4},
pages = {},
pmid = {37992380},
issn = {2160-9381},
abstract = {INTRODUCTION: Both Androgenetic alopecia (AGA) and age-related macular degeneration (AMD) shared the microinflammatory milieu and increased oxidative stress as important criteria in their pathogenesis. The monocyte/high density lipoprotein (HDL) ratio (MHR) seems to be an easy-to-calculate prognostic marker of microinflammation.<br><br>OBJECTIVES: To assess MHR in patients with AGA and its correlation to AMD in these patients, if any.<br><br>METHODS: Forty patients with AGA aged 40 years or more of both sexes and 40 control subjects participated in this case-control study. General, dermatological, and ophthalmologic examination, MHR evaluation and optical coherence tomography (OCT) were performed.<br><br>RESULTS: The mean MHR was significantly higher in AGA patients (6.98 &#xb1; 2.21) than in controls (3.82 &#xb1; 0.68) (P < 0.001). AMD was significantly higher in patients than controls (P < 0.001). Eighty percent of AGA patients were diagnosed with AMD versus 20% of control subjects. The presence of AMD in AGA was significantly related to the degree of severity of AGA in male patients (P = 0.02). The MHR was significantly higher in AGA patients found to have AMD (9.37 &#xb1; 1.1 and 7.01 &#xb1; 1.42 in the wet and dry type respectively) than those without AMD (P < 0.001).<br><br>CONCLUSIONS: AMD may develop more frequently in those with AGA. The MHR seems to be a missing link between both conditions, and could be utilized as a potential biomarker for predicting AMD in AGA patients.},
}
@article {pmid37991301,
year = {2023},
author = {Bhattacharjee, H and Das, D and Bhattacharjee, K and Buragohain, S and Javeri, H},
title = {Transmittance characteristics of transparent hydrophobic acrylic foldable intraocular lenses that were in vivo for a prolonged period of time: A UV visible spectrophotometric study.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {12},
pages = {3663-3668},
pmid = {37991301},
issn = {1998-3689},
mesh = {Humans ; Middle Aged ; *Light ; Ultraviolet Rays ; *Lenses, Intraocular ; Eye ; },
abstract = {PURPOSE: To record experimental data on the spectral transmittance characteristics of transparent hydrophobic acrylic foldable IOLs, which were in vivo for a prolonged period of time and explanted under clinical indications and also to compare the data with that of corresponding control and crystalline lens along with review of the relevant literature.<br><br>METHOD: Material and make of each of the explanted intraocular lenses (IOLs) as well as pre-explantation clinical status of the eyes were confirmed from the medical record. The transmittance of wavelength from 185 to 900 nm of each of the selected IOLs was measured using Shimadzu UV 2600 UV visible (UV-Vis) spectrophotometer in double-beam configuration and probe version 2.16 software. The data obtained were statistically analyzed.<br><br>RESULTS: The mean transmittance of 12 clinically explanted IOLs at spectral range 300-700 nm was 49.5% &#xb1; SD 6.9%. This value was 10% and 38% less than the corresponding clear (59% &#xb1; SD 0.4%) and yellow (87.5% &#xb1; SD 0.4%) control, respectively. The mean transmittance of the analytes in the UV range was 43.3 &#xb1; SD 6.9%, and it was almost similar to the control. The data showed wide variations without good correlation, and it matches with the human crystalline lens at the age range of 50-60 years. All eyes were otherwise healthy, and none had age-related macular degeneration.<br><br>CONCLUSION: In comparison with fresh IOL with a yellow filter, light transmittance at the spectral range 300-700 nm was found decreased in all the IOLs, which were in vivo for an average period of 12.25 &#xb1; 4.4 years. All IOLs transmitted variable amounts of UV radiation. More data are required for further analysis on the subject.},
}
@article {pmid37990840,
year = {2023},
author = {Chang, YY and Wang, M and Yeh, JH and Tsou, SC and Chen, TC and Hsu, MY and Lee, YJ and Wang, I and Lin, HW},
title = {The protective effects of beta-mangostin against sodium iodate-induced retinal ROS-mediated apoptosis through MEK/ERK and p53 signaling pathways.},
journal = {Food &amp; function},
volume = {14},
number = {24},
pages = {10896-10909},
doi = {10.1039/d3fo03568a},
pmid = {37990840},
issn = {2042-650X},
mesh = {Animals ; Reactive Oxygen Species/metabolism ; Caspase 3/genetics/metabolism ; *Tumor Suppressor Protein p53/genetics/metabolism ; Retinal Pigment Epithelium ; Hydrogen Peroxide/metabolism ; Apoptosis ; Oxidative Stress ; Signal Transduction ; *Mitochondrial Diseases ; Mitogen-Activated Protein Kinase Kinases/metabolism ; },
abstract = {Previous studies have indicated that NaIO3 induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces. Beta-mangostin (BM) is a xanthone-type natural compound isolated from Cratoxylum arborescens. The influence of BM on NaIO3-induced oxidative stress damage in ARPE-19 cells has not yet been elucidated. In this study, we investigated how BM protects ARPE-19 cells from NaIO3-induced ROS-mediated apoptosis. Our results revealed that BM notably improved cell viability and prevented ARPE-19 cell mitochondrial dysfunction mediated-apoptosis induced by NaIO3; it was mediated by significantly reduced NaIO3-upregulated ROS, cellular H2O2 production and improved downregulated glutathione and catalase activities. Furthermore, we found that BM could suppress the expression of Bax, cleaved PARP, and cleaved caspase-3 by decreasing phosphorylation of MEK/ERK and p53 expression in NaIO3-induced ARPE-19 cells. At the same time, we also used MEK inhibitors (PD98059) to confirm the above phenomenon. Moreover, our animal experiments revealed that BM prevented NaIO3 from causing retinal deformation; it led to thicker outer and inner nuclear layers and downregulated cleaved caspase-3 expression compared to the group receiving NaIO3 only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO3-induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways.},
}
@article {pmid37990182,
year = {2023},
author = {Sun, Z and Yang, Y and Lin, B and Huang, Y and Zhou, R and Yang, C and Li, Y and Huang, S and Liu, X},
title = {Comparative efficacy of aflibercept and ranibizumab in the treatment of age-related macular degeneration with retinal pigment epithelial detachment: a systematic review and network meta-analysis.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {473},
pmid = {37990182},
issn = {1471-2415},
support = {2020YFC2008200//National Key R&amp;D Program of China/ ; 2020YFC2008200//National Key R&amp;D Program of China/ ; },
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; *Retinal Detachment/drug therapy ; Vascular Endothelial Growth Factor A ; Retinal Pigment Epithelium ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; },
abstract = {OBJECTIVES: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) in treatment of age-related macular degeneration (AMD) with retinal pigment epithelial detachment (PED).<br><br>METHODS: Systematic review identifying studies comparing intravitreal ranibizumab (IVR), intravitreal aflibercept (IVA) and intravitreal conbercept (IVC) published before Mar 2022.<br><br>RESULTS: One randomized controlled trial and 6 observational studies were selected for meta-analysis (1,069 patients). The change of best corrected visual acuity (BCVA) in IVA 2.0&#xa0;mg group was better than IVR 0.5&#xa0;mg (average difference 0.07) and IVR 2.0&#xa0;mg (average difference 0.10), the differences were statistically significant. The change of the height of PED in IVA 2.0 group was better than IVR 0.5 group (average difference 45.30), the difference was statistically significant. The proportion of patients without PED at last visit in IVA 2.0 group were better than those in IVR 2.0 group (hazard ratio 1.91), the difference was statistically significant. There was no significant difference compared with IVR 0.5 group (hazard ratio 1.45). IVA required fewer injections than IVR, with a mean difference of -1.58.<br><br>CONCLUSIONS: IVA appears to be superior to IVR in improvement of BCVA, height decrease of PED and regression of PED with less injections in nAMD with PED.},
}
@article {pmid37990107,
year = {2023},
author = {Chouraqui, M and Crincoli, E and Miere, A and Meunier, IA and Souied, EH},
title = {Deep learning model for automatic differentiation of EMAP from AMD in macular atrophy.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {20354},
pmid = {37990107},
issn = {2045-2322},
mesh = {Humans ; Retrospective Studies ; Artificial Intelligence ; *Deep Learning ; *Geographic Atrophy/diagnosis ; Fluorescein Angiography ; *Macular Degeneration/diagnostic imaging ; Fundus Oculi ; Atrophy ; },
abstract = {To create a deep learning (DL) classifier pre-trained on fundus autofluorescence (FAF) images that can assist the clinician in distinguishing age-related geographic atrophy from extensive macular atrophy and pseudodrusen-like appearance (EMAP). Patients with complete outer retinal and retinal pigment epithelium atrophy secondary to either EMAP (EMAP Group) or to dry age related macular degeneration (AMD group) were retrospectively selected. Fovea-centered posterior pole (30° × 30°) and 55° × 55° degree-field-of-view FAF images of sufficiently high quality were collected and used to train two different deep learning (DL) classifiers based on ResNet-101 design. Testing was performed on a set of images coming from a different center. A total of 300 patients were recruited, 135 belonging to EMAP group and 165 belonging to AMD group. The 30° × 30° FAF based DL classifier showed a sensitivity of 84.6% and a specificity of 85.3% for the diagnosis of EMAP. The 55° × 55° FAF based DL classifier showed a sensitivity of 90% and a specificity of 84.6%, a performance that was significantly higher than that of the 30° × 30° classifer (p = 0.037). Artificial intelligence can accurately distinguish between atrophy caused by AMD or by EMAP on FAF images. Its performance are improved using wide field acquisitions.},
}
@article {pmid37989493,
year = {2024},
author = {Reiter, GS and Mares, V and Leingang, O and Fuchs, P and Bogunovic, H and Barthelmes, D and Schmidt-Erfurth, U},
title = {Long-term effect of fluid volumes during the maintenance phase in neovascular age-related macular degeneration: results from Fight Retinal Blindness!.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {59},
number = {5},
pages = {350-357},
doi = {10.1016/j.jcjo.2023.10.017},
pmid = {37989493},
issn = {1715-3360},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Fluorescein Angiography/methods ; Follow-Up Studies ; Fundus Oculi ; *Intravitreal Injections ; Ranibizumab/administration &amp; dosage ; Retrospective Studies ; *Subretinal Fluid ; Time Factors ; *Tomography, Optical Coherence/methods ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity/physiology ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; },
abstract = {OBJECTIVE: To investigate the effect of macular fluid volumes (subretinal fluid [SRF], intraretinal fluid [IRF], and pigment epithelium detachment [PED]) after initial treatment on functional and structural outcomes in neovascular age-related macular degeneration in a real-world cohort from Fight Retinal Blindness!<br><br>METHODS: Treatment-naive neovascular age-related macular degeneration patients from Fight Retinal Blindness! (Z&#xfc;rich, Switzerland) were included. Macular fluid on optical coherence tomography was automatically quantified using an approved artificial intelligence algorithm. Follow-up of macular fluid, number of anti-vascular endothelial growth factor treatments, effect of fluid volumes after initial treatment (high, top 25%; low, bottom 75%) on best-corrected visual acuity, and development of macular atrophy and fibrosis was investigated over 48 months.<br><br>RESULTS: A total of 209 eyes (mean age, 78.3 years) were included. Patients with high IRF volumes after initial treatment differed by -2.6 (p&#x202f;=&#x202f;0.021) and -7.4 letters (p&#x202f;=&#x202f;0.007) at months 12 and 48, respectively. Eyes with high IRF received significantly more treatments (+1.6 [p < 0.001] and +5.3 [p&#x202f;=&#x202f;0.002] at months 12 and 48, respectively). Patients with high SRF or PED had comparable best-corrected visual acuity outcomes but received significantly more treatments for SRF (+2.4 [p < 0.001] and +11.4 [p < 0.001] at months 12 and 48, respectively) and PED (+1.2 [p&#x202f;=&#x202f;0.001] and +7.8 [p < 0.001] at months 12 and 48, respectively).<br><br>DISCUSSION: Patients with high macular fluid after initial treatment are at risk of losing vision that may not be compensable with higher treatment frequency for IRF. Higher treatment frequency for SRF and PED may result in comparable treatment outcomes. Quantification of macular fluid in all compartments is essential to detect eyes at risk of aggressive disease.},
}
@article {pmid37989109,
year = {2023},
author = {Zhang, M and Wu, J and Wang, Y and Wan, X and Liu, H and Sun, X},
title = {Identification of Cuproptosis-Related circRNA-miRNA-mRNA Network in Laser-Induced Choroidal Neovascularization Models and in Peripheral Blood Mononuclear Cells of Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {66},
number = {1},
pages = {1417-1432},
doi = {10.1159/000535170},
pmid = {37989109},
issn = {1423-0259},
mesh = {Animals ; Mice ; Humans ; *MicroRNAs/genetics ; RNA, Circular/genetics ; RNA, Messenger/genetics/metabolism ; Leukocytes, Mononuclear/metabolism ; *Macular Degeneration/genetics ; },
abstract = {INTRODUCTION: The aims of this study were to investigate the molecular alterations of cuproptosis-related genes and to construct the cuproptosis-related circular RNA (circRNA)-microRNA (miRNA)-mRNA networks in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: The transcriptional profiles of laser-induced choroid neovascularization (CNV) mouse models and nAMD patient samples were obtained from sequencing and from the GEO database (GSE146887), respectively. The expression levels of ten cuproptosis-related genes (FDX1, DLAT, LIAS, DLD, PDHB, MTF1, CDKN2A, GLS, LIPT1, and PDHA1) were extracted and verified in both mouse CNV models and patient peripheral blood mononuclear cells (PBMCs) samples. The cuproptosis-related circRNA-miRNA-mRNA network was further constructed based on miRNet database, the dataset GSE131646 of small RNA expression profile, and the dataset GSE140178 of circRNA expression profile in mouse CNV models.<br><br>RESULTS: The significant upregulation of Cdkn2a and Mtf1 and the downregulation of other 5 cuproptosis-related genes were verified in the mouse CNV model, but only CDKN2A significantly upregulated in PBMCs of patients with nAMD. Four miRNAs were detected in the intersection between miRNet prediction and sequencing data: miR-129-5p, miR-129-2-3p, miR-182-5p, and miR-615-3p. There were 9 circRNAs at the intersection of hsa-miR-182-5p and hsa-miR-615-3p predictions, one circRNA predicted by hsa-miR-129-5p and GSE140178 (hsa-circASH1L), and one circRNA predicted by hsa-miR-182-5p and hsa-miR-615-3p (hsa-circNPEPPS).<br><br>CONCLUSION: This study suggested the repression of cuproptosis in nAMD pathologies and constructed a cuproptosis-related network of 8 cuproptosis-related genes, 4 miRNAs, and 11 circRNAs.},
}
@article {pmid37988105,
year = {2023},
author = {Liuska, PJ and Rämö, JT and Lemmelä, S and Kaarniranta, K and Uusitalo, H and Lahtela, E and Daly, MJ and Harju, M and Palotie, A and Turunen, JA and , },
title = {Association of APOE Haplotypes With Common Age-Related Ocular Diseases in 412,171 Individuals.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {14},
pages = {33},
pmid = {37988105},
issn = {1552-5783},
mesh = {Humans ; *Apolipoprotein E4/genetics ; Eye ; *Glaucoma/genetics ; *Glaucoma, Open-Angle/genetics ; Haplotypes ; *Macular Degeneration/genetics ; },
abstract = {PURPOSE: Apolipoprotein E4 (APOE4), a known risk factor for Alzheimer's disease, has controversially been associated with reduced risk of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). Here, we sought to systematically quantify the associations of APOE haplotypes with age-related ocular diseases and to assess their scope and age-dependency.<br><br>METHODS: We included genetic and registry data from 412,171 Finnish individuals in the FinnGen study. Disease endpoints were defined using nationwide registries. APOE genotypes were directly genotyped using Illumina and Affymetrix arrays or imputed using a custom Finnish reference panel. We evaluated the disease associations of APOE genotypes containing &#x3b5;2 (without &#x3b5;4) and &#x3b5;4 (without &#x3b5;2) compared with the &#x3b5;3&#x3b5;3 genotype using logistic regressions stratified by age.<br><br>RESULTS: APOE &#x3b5;4 enriched haplotypes were inversely associated with overall glaucoma (odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.92-0.99, P = 0.0047), and its subtypes POAG (OR = 0.95, P = 0.027), normal-tension glaucoma (OR = 0.87, P = 0.0058), and suspected glaucoma (OR = 0.95, P = 0.014). Individuals with the &#x3b5;4 allele also had lower odds for AMD (OR = 0.80, 95% CI = 0.76-0.84, P < 0.001), seen both in dry and neovascular subgroups. A slight negative association was also detected in senile cataract, but this was not reproducible in age-group analyses.<br><br>CONCLUSIONS: Our results support prior evidence of the inverse association of APOE &#x3b5;4 with glaucoma, but the association was weaker than for AMD. We could not show an association with exfoliation glaucoma, supporting the hypothesis that APOE may be involved in regulating retinal ganglion cell degeneration rather than intraocular pressure.},
}
@article {pmid37988102,
year = {2024},
author = {Heinke, A and Zhang, H and Deussen, D and Galang, CMB and Warter, A and Kalaw, FGP and Bartsch, DG and Cheng, L and An, C and Nguyen, T and Freeman, WR},
title = {ARTIFICIAL INTELLIGENCE FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-BASED DISEASE ACTIVITY PREDICTION IN AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {3},
pages = {465-474},
pmid = {37988102},
issn = {1539-2864},
support = {P30EY022589/EY/NEI NIH HHS/United States ; R01EY033847/GF/NIH HHS/United States ; P30 EY022589/EY/NEI NIH HHS/United States ; R01 EY016323/EY/NEI NIH HHS/United States ; OT2 OD032644/OD/NIH HHS/United States ; R01EY016323/GF/NIH HHS/United States ; R01 EY033847/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Artificial Intelligence ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Cross-Sectional Studies ; Fluorescein Angiography/methods ; *Choroidal Neovascularization/diagnosis/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Geographic Atrophy ; },
abstract = {PURPOSE: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans.<br><br>METHODS: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories.<br><br>RESULTS: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was 0.4286 active choroidal neovascularization, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, and 0.9762, respectively. The overall AI classification prediction was significantly better than the human (odds ratio = 1.95, P = 0.0021).<br><br>CONCLUSION: These data show that choroidal neovascularization morphology can be used to predict disease activity by AI; longitudinal studies are needed to better understand the evolution of choroidal neovascularization and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.},
}
@article {pmid37987893,
year = {2024},
author = {Li, B and Fan, K and Zhang, T and Wu, Z and Zeng, S and Zhao, M and Ren, Q and Zheng, D and Wang, L and Liu, X and Han, M and Song, Y and Ye, J and Pei, C and Yi, J and Wang, X and Peng, H and Zhang, H and Zhou, Z and Liang, X and Yu, F and Wu, M and Li, C and Lei, C and Hao, J and Tang, L and Yuan, H and Cai, S and Li, Q and Zhong, J and Li, S and Liu, L and Ke, M and Wang, J and Wang, H and Zhu, M and Wang, Z and Yan, Y and Wang, F and Chen, Y},
title = {Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.},
journal = {Ophthalmology and therapy},
volume = {13},
number = {1},
pages = {353-366},
pmid = {37987893},
issn = {2193-8245},
abstract = {INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged&#x2009;&#x2265;&#x2009;50&#xa0;years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2&#xa0;mg (0.05&#xa0;ml) in the study eye every 4&#xa0;weeks for the first 3&#xa0;months, followed by 2&#xa0;mg every 8&#xa0;weeks until week 48, stratified by baseline BCVA&#x2009;&#x2265;&#x2009;or&#x2009;<&#x2009;45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was&#x2009;&#xb1;&#x2009;5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated.<br><br>RESULTS: A total of 366 patients were enrolled (QL1207 group, n&#x2009;=&#x2009;185; aflibercept group, n&#x2009;=&#x2009;181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes&#xa0;was -&#x2009;1.1 letters&#xa0;(95% confidence interval -&#x2009;3.0 to 0.7; P&#x2009;=&#x2009;0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups.<br><br>CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).},
}
@article {pmid37986876,
year = {2023},
author = {Hass, DT and Pandey, K and Engel, A and Horton, N and Robbings, BM and Lim, R and Sadilek, M and Zhang, Q and Autterson, GA and Miller, JML and Chao, JR and Hurley, JB},
title = {Acetyl-CoA carboxylase Inhibition increases RPE cell fatty acid oxidation and limits apolipoprotein efflux.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.11.07.566117},
pmid = {37986876},
issn = {2692-8205},
support = {K08 EY033420/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: In age-related macular degeneration (AMD) and Sorsby's fundus dystrophy (SFD), lipid-rich deposits known as drusen accumulate under the retinal pigment epithelium (RPE). Drusen may contribute to photoreceptor and RPE degeneration in AMD and SFD. We hypothesize that stimulating β-oxidation in RPE will reduce drusen accumulation. Inhibitors of acetyl-CoA carboxylase (ACC) stimulate β-oxidation and diminish lipid accumulation in fatty liver disease. In this report we test the hypothesis that an ACC inhibitor, Firsocostat, limits the accumulation of lipid deposits in cultured RPE cells.<br><br>METHODS: We probed metabolism and cellular function in mouse RPE-choroid, human fetal- derived RPE cells, and induced pluripotent stem cell-derived RPE cells. We used [13] C6-glucose and [13] C16-palmitate to determine the effects of Firsocostat on glycolytic, Krebs cycle, and fatty acid metabolism. [13] C labeling of metabolites in these pathways were analyzed using gas chromatography-linked mass spectrometry. We quantified ApoE and VEGF release using enzyme-linked immunosorbent assays. Immunostaining of sectioned RPE was used to visualize ApoE deposits. RPE function was assessed by measuring the trans-epithelial electrical resistance (TEER).<br><br>RESULTS: ACC inhibition with Firsocostat increases fatty acid oxidation and remodels lipid composition, glycolytic metabolism, lipoprotein release, and enhances TEER. When human serum is used to induce sub-RPE lipoprotein accumulation, fewer lipoproteins accumulate with Firsocostat. In a culture model of Sorsby's fundus dystrophy, Firsocostat also stimulates fatty acid oxidation, improves morphology, and increases TEER.<br><br>CONCLUSIONS: Firsocostat remodels intracellular metabolism and improves RPE resilience to serum-induced lipid deposition. This effect of ACC inhibition suggests that it could be an effective strategy for diminishing drusen accumulation in the eyes of patients with AMD.},
}
@article {pmid37986170,
year = {2023},
author = {Antonio-Aguirre, B and Arevalo, JF},
title = {Treating patients with geographic atrophy: are we there yet?.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {72},
pmid = {37986170},
issn = {2056-9920},
abstract = {Geographic atrophy (GA) is a progressive degenerative disease that significantly contributes to visual impairment in individuals aged 50 years and older. The development of GA is influenced by various modifiable and non-modifiable risk factors, including age, smoking, and specific genetic variants, particularly those related to the complement system regulators. Given the multifactorial and complex nature of GA, several treatment approaches have been explored, such as complement inhibition, gene therapy, and cell therapy. The recent approval by the Food and Drug Administration of pegcetacoplan, a complement C3 inhibitor, marks a significant breakthrough as the first approved treatment for GA. Furthermore, numerous interventions are currently in phase II or III trials, alongside this groundbreaking development. In light of these advancements, this review provides a comprehensive overview of GA, encompassing risk factors, prevalence, genetic associations, and imaging characteristics. Additionally, it delves into the current landscape of GA treatment, emphasizing the latest progress and future considerations. The goal of starting this discussion is to ultimately identify the most suitable candidates for each therapy, highlight the importance of tailoring treatments to individual cases, and continue monitoring the long-term implications of these emerging interventions.},
}
@article {pmid37985993,
year = {2023},
author = {Deng, W and Yi, C and Pan, W and Liu, J and Qi, J and Chen, J and Zhou, Z and Duan, Y and Ning, X and Li, J and Ye, C and Chen, Z and Xu, H},
title = {Vascular Cell Adhesion Molecule-1 (VCAM-1) contributes to macular fibrosis in neovascular age-related macular degeneration through modulating macrophage functions.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {20},
number = {1},
pages = {65},
pmid = {37985993},
issn = {1742-4933},
support = {MR/W004682/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a major cause of blindness in the elderly. The disease is due to the growth of abnormal blood vessels into the macula, leading to the loss of central vision. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors (e.g., anti-VEGF) is the standard of care for nAMD. However, nearly 50% of patients do not respond or respond poorly to the therapy. More importantly, up to 70% of nAMD patients develop macular fibrosis after 10 years of anti-VEGF therapy. The underlying mechanism of nAMD-mediated macular fibrosis is unknown although inflammation is known to play an important role in the development of abnormal macular blood vessels and its progression to fibro-vascular membrane. In this study, we measured the intraocular levels of adhesion molecule VCAM-1, ICAM-1, CD44, CD62L, and CD62P in nAMD patients with and without macular fibrosis and investigated the link between the levels of adhesion molecule and clinical features (e.g., visual improvement, retinal thickness, etc.). We further investigated the effect of VCAM-1 in macrophage function in vitro and the development of subretinal fibrosis in vivo using a two-stage laser-induced protocol.<br><br>RESULTS: The aqueous levels of ICAM-1, VCAM-1, CD44, and CD62L were significantly higher in nAMD patients compared to cataract controls. The aqueous level of VCAM-1 (but not other adhesion molecules) was significantly higher in patients with macular fibrosis than those without and the level correlated positively with the retinal thickness. VCAM-1 was highly expressed at the lesion site in the mouse model of subretinal fibrosis. Blocking VCAM-1 or its receptor VLA-4 significantly&#xa0;prevented macrophage infiltration and reduced subretinal fibrosis in vivo. VCAM-1 induced macrophage migration and upregulated the expression of Arg-1, Mmp12 and Il6 but down-regulated the expression of iNOS and Il1b in macrophages.<br><br>CONCLUSIONS: VCAM-1 may contribute to the development of macular fibrosis in nAMD patients by modulating macrophage functions, including migration and profibrotic polarization.},
}
@article {pmid37984593,
year = {2023},
author = {Heljak, MK and Swieszkowski, W},
title = {Investigating bevacizumab and its fragments sustained release from intravitreal administrated PLGA Microspheres: A modeling approach.},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V},
volume = {193},
number = {},
pages = {285-293},
doi = {10.1016/j.ejpb.2023.11.015},
pmid = {37984593},
issn = {1873-3441},
mesh = {Bevacizumab ; Delayed-Action Preparations ; Microspheres ; Polylactic Acid-Polyglycolic Acid Copolymer ; *Retina ; Intravitreal Injections ; },
abstract = {Intravitreal administrated bevacizumab has emerged as an effective antibody for suppressing VEGF expression in age-related macular degeneration (AMD) therapy. This study discusses certain issues related to the sustained release of bevacizumab from intravitreal poly(lactic-co-glycolic acid) (PLGA) microspheres. A computational model elucidating the ocular kinetics of bevacizumab is demonstrated, wherein the release of the drug from PLGA microspheres is modeled using the Koizumi approach, complemented by an empirical model that links the kinetics of bevacizumab release to a size-dependent hydrolytic degradation of the drug-loaded polymeric microparticles. The results of the simulation were then rigorously validated against experimental data. The as-developed model proved remarkably accurate in predicting the time-concentration profiles obtained following the intravitreal injection of PLGA microspheres of significantly different sizes. Notably, the time-concentration profiles of bevacizumab in distinct ocular tissues were almost unaffected by the size of the intravitreally administered PLGA microparticles. Furthermore, the model successfully predicted the retinal concentration of bevacizumab and its fragments (e.g., ranibizumab) administrated in the form of a solution. As such, this model for drug sustained release and ocular transport holds tremendous potential for facilitating the reliable evaluation of planned anti-VEGF therapies.},
}
@article {pmid37982768,
year = {2023},
author = {Sobh, M and Lagali, PS and Ghiasi, M and Montroy, J and Dollin, M and Hurley, B and Leonard, BC and Dimopoulos, I and Lafreniere, M and Fergusson, DA and Lalu, MM and Tsilfidis, C},
title = {Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {11},
pages = {24},
pmid = {37982768},
issn = {2164-2591},
mesh = {Humans ; *Retinal Degeneration/therapy ; Dependovirus/genetics ; *Macular Degeneration/drug therapy ; *Retinitis Pigmentosa ; Genetic Therapy/adverse effects ; },
abstract = {PURPOSE: This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV).<br><br>METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1.<br><br>RESULTS: Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%).<br><br>CONCLUSIONS: AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up.<br><br>TRANSLATIONAL RELEVANCE: This systematic review will help to inform and guide future clinical trials.},
}
@article {pmid37981235,
year = {2024},
author = {Brown, GC and Brown, MM and Monigle, MC},
title = {Cost-Utility Analysis of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {5},
pages = {431-446},
doi = {10.1016/j.oret.2023.11.002},
pmid = {37981235},
issn = {2468-6530},
mesh = {Aged ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage/economics ; *Cost-Benefit Analysis ; Drug Delivery Systems/economics ; Follow-Up Studies ; *Intravitreal Injections ; Quality of Life ; Quality-Adjusted Life Years ; *Ranibizumab/administration &amp; dosage/economics ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/economics/diagnosis ; },
abstract = {PURPOSE: To quantify the cost-utility ratio of the ranibizumab Port Delivery System (PDS; SUSVIMO) versus intravitreal ranibizumab injections for treating neovascular age-related macular degeneration (nAMD) based upon Archway Phase 3 Trial data.<br><br>DESIGN: Cost-utility analysis.<br><br>SUBJECTS: Archway Phase 3 Clinical Trial nAMD participants previously responsive to anti-VEGF therapy were randomized 3:2. Two hundred forty received PDS refills q 24 weeks and 162 received ranibizumab injections.<br><br>METHODS: Ophthalmic patient, time tradeoff utilities, direct medical and societal cost perspectives, 12-year, 1-year, and 5-year timelines, United States 2022 real dollars, and a 3% annual discount rate were employed. Utilities were adjusted for nAMD conversion in fellow eyes during the 12-year, mean participant life expectancy. Premature death associated with severe vision loss was integrated as per the population-based Salisbury Eye Evaluation Study.<br><br>MAIN OUTCOME MEASURES: Quality-adjusted life-year (QALY) accruals, costs, and incremental and average cost-utility ratios in $/QALY (dollars expended per QALY gained).<br><br>RESULTS: Versus no therapy, the 1-year PDS QALY gain was 0.0156 (6.8%) versus 0.0063 (0.82%) for intravitreal injections (P < 0.001), whereas the respective 12-year QALY gains were 1.714 (28%) and 1.639 (26.8%) (P&#xa0;= 0.99). One-year direct PDS ophthalmic costs totaled $21 825 with 2 ranibizumab fills, whereas ranibizumab injection therapy totaled $18 405 with 11.8 injections. The 1-year incremental PDS $/QALY versus injections was cost effective at $75 497/QALY. Five-year PDS therapy was not incrementally cost effective at $304 108/QALY, nor was the 12-year therapy at $761 646/QALY. Average 12-year cost-utility ratios were $78&#xa0;773/QALY for the PDS and $47 917/QALY for injection therapy. Adding&#xa0;-$476 442 12-year offsetting societal costs netted $314 521 to society per PDS participant versus $370 958 per participant for injection therapy.<br><br>CONCLUSIONS: Ranibizumab PDS therapy was not incrementally cost effective versus ranibizumab injection therapy at 12 or 5 years but was at 1 year. Injection therapy had a more favorable 12-year average cost-utility ratio. Vision gain was the major determinant of participant value gain and was the same for both interventions. Both interventions were highly cost effective utilizing average cost-utility analysis with the societal cost perspective.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37981234,
year = {2024},
author = {Drakopoulos, M and Zhang, KX and Zhang, DL and Nadel, A and Bains, HK and Marchese, A and Mirza, RG},
title = {Independence of Ocular Biomarkers of Cardiac Risk in Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {3},
pages = {309-311},
doi = {10.1016/j.oret.2023.11.003},
pmid = {37981234},
issn = {2468-6530},
mesh = {Humans ; *Macular Degeneration/diagnosis ; *Retinal Drusen ; Eye ; Biomarkers ; },
}
@article {pmid37980501,
year = {2023},
author = {Ferro Desideri, L and Roth, J and Zinkernagel, M and Anguita, R},
title = {"Application and accuracy of artificial intelligence-derived large language models in patients with age related macular degeneration".},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {71},
pmid = {37980501},
issn = {2056-9920},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) affects millions of people globally, leading to a surge in online research of putative diagnoses, causing potential misinformation and anxiety in patients and their parents. This study explores the efficacy of artificial intelligence-derived large language models (LLMs) like in addressing AMD patients' questions.<br><br>METHODS: ChatGPT 3.5 (2023), Bing AI (2023), and Google Bard (2023) were adopted as LLMs. Patients' questions were subdivided in two question categories, (a) general medical advice and (b) pre- and post-intravitreal injection advice and classified as (1) accurate and sufficient (2) partially accurate but sufficient and (3) inaccurate and not sufficient. Non-parametric test has been done to compare the means between the 3 LLMs scores and also an analysis of variance and reliability tests were performed among the 3 groups.<br><br>RESULTS: In category a) of questions, the average score was 1.20 (&#xb1;&#x2009;0.41) with ChatGPT 3.5, 1.60 (&#xb1;&#x2009;0.63) with Bing AI and 1.60 (&#xb1;&#x2009;0.73) with Google Bard, showing no significant differences among the 3 groups (p&#x2009;=&#x2009;0.129). The average score in category b was 1.07 (&#xb1;&#x2009;0.27) with ChatGPT 3.5, 1.69 (&#xb1;&#x2009;0.63) with Bing AI and 1.38 (&#xb1;&#x2009;0.63) with Google Bard, showing a significant difference among the 3 groups (p&#x2009;=&#x2009;0.0042). Reliability statistics showed Chronbach's &#x3b1; of 0.237 (range 0.448, 0.096-0.544).<br><br>CONCLUSION: ChatGPT 3.5 consistently offered the most accurate and satisfactory responses, particularly with technical queries. While LLMs displayed promise in providing precise information about AMD; however, further improvements are needed especially in more technical questions.},
}
@article {pmid37980349,
year = {2023},
author = {Li, HY and Wei, TT and Zhuang, M and Tan, CY and Xie, TH and Cai, J and Yao, Y and Zhu, L},
title = {Iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway.},
journal = {Cell death discovery},
volume = {9},
number = {1},
pages = {419},
pmid = {37980349},
issn = {2058-7716},
support = {82201220//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, is prospectively associated with retinal pigment epithelial (RPE) senescence. However, the mechanism of RPE cell senescence remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells and D-galactose-treated C57 mice were used to examine the cause of elevated iron in RPE cell senescence. Ferric ammonium citrate (FAC)-treated ARPE-19 cells and C57 mice were used to elucidated the mechanism of iron overload-induced RPE cell senescence. Molecular biology techniques for the assessment of iron metabolism, cellular senescence, autophagy, and mitochondrial function in vivo and in vitro. We found that iron level was increased during the senescence process. Ferritin, a major iron storage protein, is negatively correlated with intracellular iron levels and cell senescence. NCOA4, a cargo receptor for ferritinophagy, mediates degradation of ferritin and contributes to iron accumulation. Besides, we found that iron overload leads to mitochondrial dysfunction. As a result, mitochondrial DNA (mtDNA) is released from damaged mitochondria to cytoplasm. Cytoplasm mtDNA activates the cGAS-STING pathway and promotes inflammatory senescence-associated secretory phenotype (SASP) and cell senescence. Meanwhile, iron chelator Deferoxamine (DFO) significantly rescues RPE senescence and retinopathy induced by FAC or D-gal in mice. Taken together, these findings imply that iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Inhibiting iron accumulation may represent a promising therapeutic approach for age-related diseases such as AMD.},
}
@article {pmid37975850,
year = {2023},
author = {Acar, IE and Galesloot, TE and Luhmann, UFO and Fauser, S and Gayán, J and den Hollander, AI and Nogoceke, E},
title = {Whole Genome Sequencing Identifies Novel Common and Low-Frequency Variants Associated With Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {14},
pages = {24},
pmid = {37975850},
issn = {1552-5783},
mesh = {Humans ; Genotype ; *Macular Degeneration/genetics ; Genetic Testing ; Whole Genome Sequencing ; *Asthma/genetics ; Polymorphism, Single Nucleotide ; Complement Factor H/genetics ; Genetic Predisposition to Disease ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics ; },
abstract = {PURPOSE: To identify associations of common, low-frequency, and rare variants with advanced age-related macular degeneration (AMD) using whole genome sequencing (WGS).<br><br>METHODS: WGS data were obtained for 2123 advanced AMD patients (participants of clinical trials for advanced AMD) and 2704 controls (participants of clinical trials for asthma [N = 2518] and Alzheimer's disease [N = 186]), and joint genotype calling was performed, followed by quality control of the dataset. Single variant association analyses were performed for all identified common, low-frequency, and rare variants. Gene-based tests were executed for rare and low-frequency variants using SKAT-O and three groups of variants based on putative impact information: (1) all variants, (2) modifier impact variants, and (3) high- and moderate-impact variants. To ascertain independence of the identified associations from previously reported AMD and asthma loci, conditional analyses were performed.<br><br>RESULTS: Previously identified AMD variants at the CFH, ARMS2/HTRA1, APOE, and C3 loci were associated with AMD at a genome-wide significance level. We identified new single variant associations for common variants near the PARK7 gene and in the long non-coding RNA AC103876.1, and for a rare variant near the TENM3 gene. In addition, gene-based association analyses identified a burden of modifier variants in eight intergenic and gene-spanning regions and of high- and moderate-impact variants in the C3, CFHR5, SLC16A8, and CFI genes.<br><br>CONCLUSIONS: We describe the largest WGS study in AMD to date. We confirmed previously identified associations and identified several novel associations that are worth exploring in further follow-up studies.},
}
@article {pmid37975315,
year = {2024},
author = {Karesvuo, M and Sorsa, T and Tuuminen, R},
title = {Association between Oral Active-Matrix Metalloproteinase-8 Levels and Subretinal Fibrosis among Wet Age-Related Macular Degeneration Patients.},
journal = {Current eye research},
volume = {49},
number = {3},
pages = {288-294},
doi = {10.1080/02713683.2023.2280442},
pmid = {37975315},
issn = {1460-2202},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Matrix Metalloproteinase 8/therapeutic use ; Retrospective Studies ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Fibrosis ; Tomography, Optical Coherence/methods ; Subretinal Fluid ; Ranibizumab ; },
abstract = {PURPOSE: Periodontitis causes low-grade systemic inflammation and has been associated with elevated active-matrix metalloproteinase (aMMP-8) levels, blood-ocular barrier breakdown and a risk of wet age-related macular degeneration. To assess the association between aMMP-8 levels and macular status among patients with wet age-related macular degeneration (AMD).<br><br>METHODS: Patients on anti-VEGF treatment for wet AMD were enrolled for oral aMMP-8 rinse test in Mehil&#xe4;inen Private Hospital, Helsinki, Finland. Macular status was examined from spectral-domain optical coherence tomography (SD-OCT) scans by a medical retina specialist and aMMP-8 levels were analyzed with chairside point-of-care oral rinse (PerioSafe&#xae;) test and real-time quantitated by a dentist using the ORALyzer&#xae;- reader with a 10&#x2009;ng/ml cut-off for aMMP-8 activity.<br><br>RESULTS: Elevated aMMP-8 levels were found in 10 out of 32 patients. Age, gender, anti-VEGF (bevacizumab or aflibercept) distribution, cumulative number of anti-VEGF injections and treatment interval were comparable between patients with aMMP-8 levels below and above the point-of-care level. Macular status differed in regard to aMMP-8 activity; among patients with aMMP-8 levels below the point-of-care subretinal fibrosis was found in 6 out of 22 eyes, whereas among patients with aMMP-8 levels above the point-of-care subretinal fibrosis was found in 8 out of 10 eyes (p&#x2009;=&#x2009;0.005). Respectively, the mean thickness of subretinal fibrosis at fovea was 19.5&#x2009;&#xb1;&#x2009;44.1 and 92.3&#x2009;&#xb1;&#x2009;78.3&#x2009;&#xb5;m (p&#x2009;=&#x2009;0.018). No differences were found in the presence and in the area of geographic atrophy, or fluid distribution, whereas thicknesses of serous pigment epithelial detachment (65.5&#x2009;&#xb1;&#x2009;99.5 and 12.9&#x2009;&#xb1;&#x2009;27.9&#x2009;&#xb5;m, p&#x2009;=&#x2009;0.038) and neuroretina (204.2&#x2009;&#xb1;&#x2009;57.8&#x2009;&#xb5;m and 143.0&#x2009;&#xb1;&#x2009;43.7&#x2009;&#xb5;m, p&#x2009;=&#x2009;0.006) were greater in the eyes of patients with physiological aMMP-8 levels compared to those with elevated aMMP-8 levels.<br><br>CONCLUSION: Elevated aMMP-8 levels may account for subretinal fibrosis formation in wet AMD.},
}
@article {pmid37973043,
year = {2024},
author = {Park, JY and Kim, JS and Sim, HE and Lee, SH and Na, HM and Kang, MJ and Hwang, JH},
title = {PREVALENCE AND RISK FACTORS OF AGE-RELATED MACULAR DEGENERATION FEATURES AMONG PILOTS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {3},
pages = {475-486},
doi = {10.1097/IAE.0000000000003976},
pmid = {37973043},
issn = {1539-2864},
support = {2022-1//Republic of Korea Air Force, Office of the Surgeon General/ ; },
mesh = {Humans ; Male ; Prevalence ; Cross-Sectional Studies ; Retrospective Studies ; *Macular Degeneration/diagnosis/epidemiology/etiology ; Risk Factors ; },
abstract = {PURPOSE: To investigate the prevalence and risk factors of age-related macular degeneration features among pilots of Republic of Korea Air Force.<br><br>METHODS: This retrospective, cross-sectional study was performed with a total of 2781 Republic of Korea Air Force pilots who underwent regular medical examinations between 2020 and 2021. Age-related macular degeneration features were determined and graded by fundus photographs. Risk factors were identified with logistic regression analysis in odds ratio (OR) and 95% confidence interval (CI).<br><br>RESULTS: The prevalence was 12.9% in the Republic of Korea Air Force pilots and 35.2% in those older than 50 years. Pilots with age-related macular degeneration features were positively associated with age (OR: 1.082, CI: 1.067-1.096, P < 0.001), male sex (OR: 0.229, CI: 0.056-0.939, P = 0.041), smoking (OR: 1.027, CI: 1.008-1.047, P = 0.006), flight time (OR: 1.004, CI: 1.003-1.005, P < 0.001), total cholesterol (OR: 1.004, CI: 1.000-1.007, P = 0.033), and low-density lipoprotein (OR: 1.005, CI: 1.001-1.008, P = 0.011). Aircraft type was also identified as a risk factor (OR: 0.617, CI: 0.460-0.827 for carrier, OR: 0.572, CI: 0.348-0.940 for helicopter, P = 0.002), with fighter pilots having a higher risk than carrier and helicopter pilots. The results were similar for pilots older than 50 years.<br><br>CONCLUSION: The prevalence of age-related macular degeneration features in Republic of Korea Air Force pilots was higher than in other general populations studied. Identified risk factors such as flight time and aircraft type suggest potential occupational risk of age-related macular degeneration in aviators.},
}
@article {pmid37972995,
year = {2025},
author = {Rouvas, A and Theodossiadis, P and Georgalas, I and Gouliopoulos, N},
title = {COMPLETE RESOLUTION OF SUBRETINAL FLUID OF THE FELLOW EYE AFTER AFLIBERCEPT INJECTION IN WET AGE-RELATED MACULAR DEGENERATION.},
journal = {Retinal cases &amp; brief reports},
volume = {19},
number = {1},
pages = {125-128},
doi = {10.1097/ICB.0000000000001515},
pmid = {37972995},
issn = {1937-1578},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage/therapeutic use ; *Recombinant Fusion Proteins/administration &amp; dosage/therapeutic use ; Female ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; *Intravitreal Injections ; *Subretinal Fluid ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Retrospective Studies ; *Fluorescein Angiography/methods ; Visual Acuity ; Fundus Oculi ; },
abstract = {PURPOSE: To present a case of a patient with bilateral wet age-related macular degeneration who was unilaterally treated with intravitreal aflibercept injections (IAIs) and the disease status in the fellow eye ameliorated after an IAI.<br><br>METHODS: Retrospective case report.<br><br>RESULTS: A 72-year-old woman was diagnosed with wet and dry age-related macular degeneration in her right eye and left eye, respectively. In the right eye, treatment strategy comprised three monthly IAIs, followed by reinjections according to need, whereas optical coherence tomography scans were performed before IAIs. One month after the second IAI, subretinal fluid developed in the left eye. One week later, an IAI was applied in the right eye; 2 days later, the disease status in the left eye was assessed by fluorescein angiography and optical coherence tomography. Surprisingly, in the left eye, subretinal fluid completely resolved and fluorescein angiography did not detect leakage, highlighting the absence of an active choroidal neovascularization. The short interval between IAI and the resolution of exudative phenomena in the other eye is suggestive of a beneficial effect in the contralateral eye.<br><br>CONCLUSION: In this article, we showed that an IAI had an effect to the fellow untreated eye. Our observation is consistent with active aflibercept in the systemic circulation. To the best of our knowledge, no other report in the literature has demonstrated this effect of aflibercept in wet age-related macular degeneration.},
}
@article {pmid37972955,
year = {2024},
author = {Boyer, D and Hu, A and Warrow, D and Xavier, S and Gonzalez, V and Lad, E and Rosen, RB and Do, D and Schneiderman, T and Ho, A and Munk, MR and Jaffe, G and Tedford, SE and Croissant, CL and Walker, M and Rückert, R and Tedford, CE},
title = {LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {3},
pages = {487-497},
pmid = {37972955},
issn = {1539-2864},
support = {R43 EY025508/EY/NEI NIH HHS/United States ; R43 EY025892/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Low-Level Light Therapy ; Prospective Studies ; Visual Acuity ; *Macular Degeneration/diagnosis/radiotherapy/drug therapy ; Eye ; *Geographic Atrophy/diagnosis/radiotherapy ; },
abstract = {PURPOSE: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System.<br><br>METHODS: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report.<br><br>RESULTS: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy (P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed.<br><br>CONCLUSION: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.},
}
@article {pmid37971992,
year = {2023},
author = {Gomes, DF and Curado, DDSP and Gomes, RM and Leite, BF and Ramos, MC and Silva, END},
title = {Clinical effectiveness of screening for age-related macular degeneration: A systematic review.},
journal = {PloS one},
volume = {18},
number = {11},
pages = {e0294398},
pmid = {37971992},
issn = {1932-6203},
mesh = {Humans ; Middle Aged ; *Macular Degeneration/diagnosis/prevention &amp; control ; Tomography, Optical Coherence/methods ; Treatment Outcome ; Diagnostic Techniques, Ophthalmological ; Photography ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is an eye disease that occurs in patients over 50 years old. Early diagnosis enables timely treatment to stabilize disease progression. However, the fact that the disease is asymptomatic in its early stages can delay treatment until it progresses. As such, screening in specific contexts can be an early detection tool to reduce the clinical and social impact of the disease.<br><br>OBJECTIVE: Assess the effectiveness of screening methods for early detection of AMD in adults aged 50 years or older.<br><br>METHODS: A systematic review of comparative observational studies on AMD screening methods in those aged 50 years or older, compared with no screening or any other strategy. A literature search was conducted in the MEDLINE (via PubMed), Embase, Cochrane Library and Lilacs database.<br><br>RESULTS: A total of 5,290 studies were identified, three of which met the inclusion criteria and were selected for the systematic review. A total of 8,733 individuals (16,780 eyes) were included in the analysis. The screening methods assessed were based on optical coherence tomography (OCT) compared with color fundus photography, and OCT and telemedicine testing compared to a standard eye exam.<br><br>CONCLUSION: The systematized data are limited and only suggest satisfactory performance in early screening of the population at risk of developing AMD. OCT and the telemedicine technique showed promising results in AMD screening. However, methodological problems were identified in the studies selected and the level of evidence was considered low.},
}
@article {pmid37968982,
year = {2023},
author = {Jo, DH and Lee, SH and Jeon, M and Cho, CS and Kim, DE and Kim, H and Kim, JH},
title = {Activation of Lysosomal Function Ameliorates Amyloid-β-Induced Tight Junction Disruption in the Retinal Pigment Epithelium.},
journal = {Molecules and cells},
volume = {46},
number = {11},
pages = {675-687},
pmid = {37968982},
issn = {0219-1032},
mesh = {Mice ; Animals ; *Retinal Pigment Epithelium/metabolism ; Tight Junctions/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; TOR Serine-Threonine Kinases/metabolism ; *Macular Degeneration/metabolism ; Lysosomes/metabolism ; Autophagy/physiology ; Mammals ; },
abstract = {Accumulation of pathogenic amyloid-β disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-β, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-β by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-β with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-β oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-β in vitro and in vivo. Furthermore, clearance of amyloid-β by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.},
}
@article {pmid37968771,
year = {2023},
author = {Beraldo, DP and Rezende, MP and Alexander, JG and Polido, J and Belfort, R and Cabral, T},
title = {Correlations between subfoveal choroidal thickness, macular thickness, and visual outcome in neovascular age-related macular degeneration using swept source OCT: insights from intravitreal aflibercept treatment.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {70},
pmid = {37968771},
issn = {2056-9920},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment among individuals aged 50 and above, often resulting in irreversible vision loss (1). Currently, antiangiogenic therapy is the primary treatment approach for neovascular AMD (2). The choroid has gained significant attention in recent years due to its involvement in various ocular pathologies (7). The objective of this study was to evaluate visual acuity and correlate pre-treatment variables, such as foveal thickness and choroidal thickness, with post-treatment outcomes.<br><br>MATERIALS AND METHODS: This study was designed as a prospective interventional study to investigate the changes in choroidal and macular thickness in patients with neovascular AMD who received intravitreal aflibercept injections. The study utilized medical records and employed Swept Source Optical Coherence Tomography (OCT-SS) for evaluation. The data was collected from patients treated in Presidente Prudente, Brazil, during a three-month load dose period.<br><br>RESULTS: The best-corrected mean visual acuity significantly improved from 1.0 logarithm of the minimum resolution angle (logMAR) units to 0.55 logMAR after treatment with aflibercept (p&#x2009;<&#x2009;0.001). Patients undergoing treatment exhibited a significant decrease in average macular thickness from 323&#xa0;&#x3bc;m to 232&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.001), as well as a reduction in choroidal thickness from 206&#xa0;&#x3bc;m to 172&#xa0;&#x3bc;m (p&#x2009;=&#x2009;0.031), while maintaining intraocular pressure within the normal range (p&#x2009;=&#x2009;0.719) without significant variation. Statistically significant associations were found between the difference in pre- and post-treatment choroidal thickness and the pretreatment values of macular thickness (p&#x2009;=&#x2009;0.005) and choroidal thickness (p&#x2009;=&#x2009;0.013). There was also a statistically significant correlation between the difference in pre- and post-treatment macular thickness and the pretreatment macular thickness value (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: In this study, aflibercept exhibited remarkable effectiveness in reducing macular and choroidal thickness, as evaluated using OCT-SS, and significantly improved visual acuity in patients with neovascular AMD. The assessment of both choroidal and macular changes, as well as their correlations, can provide valuable insights for clinicians, enabling them to make well-informed therapeutic decisions and effectively monitor treatment outcomes. Notably, this study contributes to the existing body of literature as the first to establish a correlation between pretreatment foveal thickness, variation in choroidal thickness, and post-treatment choroidal thickness.},
}
@article {pmid37966366,
year = {2023},
author = {Ktistakis, E and Simos, P and Tsilimbaris, MK and Plainis, S},
title = {Efficacy οf Wet Age-related Macular Degeneration Treatment οn Reading: A Pilot Study Using Eye-movement Analysis.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {100},
number = {10},
pages = {670-678},
doi = {10.1097/OPX.0000000000002064},
pmid = {37966366},
issn = {1538-9235},
mesh = {Adult ; Humans ; *Eye Movements ; Pilot Projects ; Reading ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {SIGNIFICANCE: Functional vision, as evaluated with silent passage reading speed, improves after anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with wet age-related macular antidegeneration (wAMD), reflecting primarily a concomitant reduction in the number of fixations. Implementing eye movement analysis when reading may better characterize the effectiveness of therapeutic approaches in wAMD.<br><br>PURPOSE: This study aimed to evaluate silent reading performance by means of eye fixation analysis before and after anti-VEGF treatment in wAMD patients.<br><br>METHODS: Sixteen wAMD patients who underwent anti-VEGF treatment in one eye and visual acuity (VA) better than 0.5 logMAR served as the AMD group. Twenty adults without ocular pathology served as the control group. Central retinal thickness and near VA were assessed at baseline and 3 to 4 months after their first visit. Reading performance was evaluated using short passages of 0.4-logMAR print size. Eye movements were recorded using EyeLink II video eye tracker. Data analysis included computation of reading speed, fixation duration, number of fixations, and percentage of regressions. Frequency distributions of fixation durations were analyzed with ex-Gaussian fittings.<br><br>RESULTS: In the AMD group, silent reading speed in the treated eye correlated well with central retinal thickness reduction and improved significantly by an average of 15.9 &#xb1; 28.5 words per minute (P = .04). This improvement was accompanied by an average reduction of 0.24 &#xb1; 0.38 in fixations per word (P = .03). The corresponding improvement in monocular VA was not statistically significant. Other eye fixation parameters did not change significantly after treatment. No statistically significant differences were found in the control group.<br><br>CONCLUSIONS: Visual acuity tests may underestimate the potential therapeutic effects after anti-VEGF treatment in patients with relatively good acuity who are being treated for wAMD. Evaluating silent reading performance and eye fixation parameters may better characterize the effectiveness of therapeutic approaches in wAMD patients.},
}
@article {pmid37965225,
year = {2023},
author = {Brooks, CD and Kodati, B and Stankowska, DL and Krishnamoorthy, RR},
title = {Role of mitophagy in ocular neurodegeneration.},
journal = {Frontiers in neuroscience},
volume = {17},
number = {},
pages = {1299552},
pmid = {37965225},
issn = {1662-4548},
support = {R01 EY028179/EY/NEI NIH HHS/United States ; },
abstract = {Neurons in the central nervous system are among the most metabolically active cells in the body, characterized by high oxygen consumption utilizing glucose both aerobically and anaerobically. Neurons have an abundance of mitochondria which generate adequate ATP to keep up with the high metabolic demand. One consequence of the oxidative phosphorylation mechanism of ATP synthesis, is the generation of reactive oxygen species which produces cellular injury as well as damage to mitochondria. Mitochondria respond to injury by fusion which serves to ameliorate the damage through genetic complementation. Mitochondria also undergo fission to meet an increased energy demand. Loss of mitochondria is also compensated by increased biogenesis to generate new mitochondria. Damaged mitochondria are removed by mitophagy, an autophagic process, in which damaged mitochondria are surrounded by a membrane to form an autophagosome which ultimately fuses with the lysosome resulting in degradation of faulty mitochondria. Dysregulation of mitophagy has been reported in several central nervous system disorders, including, Alzheimer's disease and Parkinson's disease. Recent studies point to aberrant mitophagy in ocular neurodegenerative disorders which could be an important contributor to the disease etiology/pathology. This review article highlights some of the recent findings that point to dysregulation of mitophagy and it's underlying mechanisms in ocular neurodegenerative diseases, including, glaucoma, age-related macular degeneration and diabetic retinopathy.},
}
@article {pmid37960299,
year = {2023},
author = {Li, C and Lu, P},
title = {Association of Gut Microbiota with Age-Related Macular Degeneration and Glaucoma: A Bidirectional Mendelian Randomization Study.},
journal = {Nutrients},
volume = {15},
number = {21},
pages = {},
pmid = {37960299},
issn = {2072-6643},
support = {No. CXTDA2017039//Jiangsu Provincial Medical Innovation Team/ ; No. 81671641//National Natural Science Foundation of China/ ; No.82271113//National Natural Science Foundation of China/ ; },
mesh = {*Glaucoma/genetics ; Eubacterium ; Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; Clostridiales ; Genome-Wide Association Study ; *Lactobacillales ; Humans ; *Macular Degeneration/genetics ; },
abstract = {The objective of this study was to examine the correlation between gut microbiota and both age-related macular degeneration (AMD) and glaucoma. Mendelian randomization studies were conducted utilizing the data sourced from the genome-wide association study (GWAS) database for the gut microbiome, AMD, and glaucoma. Single nucleotide polymorphism (SNP) estimates were summarized through five Mendelian randomization (MR) methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables (IVs). Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Inverse variance weighted (IVW) suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggest that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggest that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Likewise, reverse MR found that glaucoma led to an increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.},
}
@article {pmid37958506,
year = {2023},
author = {Lu, T and Xie, F and Huang, C and Zhou, L and Lai, K and Gong, Y and Li, Z and Li, L and Liang, J and Cong, Q and Li, W and Ju, R and Zhang, SX and Jin, C},
title = {ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization.},
journal = {International journal of molecular sciences},
volume = {24},
number = {21},
pages = {},
pmid = {37958506},
issn = {1422-0067},
support = {No. 8167086//the National Natural Science Foundation of China/ ; No.202201020624//the Science and Technology Projects of Guangzhou, China/ ; },
mesh = {Animals ; Humans ; Mice ; *Choroidal Neovascularization/genetics/metabolism ; Endoplasmic Reticulum Chaperone BiP ; Endoplasmic Reticulum Stress ; Human Umbilical Vein Endothelial Cells/pathology ; *Nicotine/pharmacology ; Retinal Pigment Epithelium/metabolism ; Heat-Shock Proteins/metabolism ; },
abstract = {Nicotine-induced endoplasmic reticulum (ER) stress in retinal pigment epithelium (RPE) cells is thought to be one pathological mechanism underlying age-related macular degeneration (AMD). ERp29 attenuates tobacco extract-induced ER stress and mitigates tight junction damage in RPE cells. Herein, we aimed to further investigate the role of ERp29 in nicotine-induced ER stress and choroidal neovascularization (CNV). We found that the expression of ERp29 and GRP78 in ARPE-19 cells was increased in response to nicotine exposure. Overexpression of ERp29 decreased the levels of GRP78 and the C/EBP homologous protein (CHOP). Knockdown of ERp29 increased the levels of GRP78 and CHOP while reducing the viability of ARPE-19 cells under nicotine exposure conditions. In the ARPE-19 cell/macrophage coculture system, overexpression of ERp29 decreased the levels of M2 markers and increased the levels of M1 markers. The viability, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were inhibited by conditioned medium from the ERp29-overexpressing group. Moreover, overexpression of ERp29 inhibits the activity and growth of CNV in mice exposed to nicotine in vivo. Taken together, our results revealed that ERp29 attenuated nicotine-induced ER stress, regulated macrophage polarization and inhibited CNV.},
}
@article {pmid37958260,
year = {2023},
author = {Alsayat, A and Elmezain, M and Alanazi, S and Alruily, M and Mostafa, AM and Said, W},
title = {Multi-Layer Preprocessing and U-Net with Residual Attention Block for Retinal Blood Vessel Segmentation.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {21},
pages = {},
pmid = {37958260},
issn = {2075-4418},
support = {223202//Al Jouf University/ ; },
abstract = {Retinal blood vessel segmentation is a valuable tool for clinicians to diagnose conditions such as atherosclerosis, glaucoma, and age-related macular degeneration. This paper presents a new framework for segmenting blood vessels in retinal images. The framework has two stages: a multi-layer preprocessing stage and a subsequent segmentation stage employing a U-Net with a multi-residual attention block. The multi-layer preprocessing stage has three steps. The first step is noise reduction, employing a U-shaped convolutional neural network with matrix factorization (CNN with MF) and detailed U-shaped U-Net (D_U-Net) to minimize image noise, culminating in the selection of the most suitable image based on the PSNR and SSIM values. The second step is dynamic data imputation, utilizing multiple models for the purpose of filling in missing data. The third step is data augmentation through the utilization of a latent diffusion model (LDM) to expand the training dataset size. The second stage of the framework is segmentation, where the U-Nets with a multi-residual attention block are used to segment the retinal images after they have been preprocessed and noise has been removed. The experiments show that the framework is effective at segmenting retinal blood vessels. It achieved Dice scores of 95.32, accuracy of 93.56, precision of 95.68, and recall of 95.45. It also achieved efficient results in removing noise using CNN with matrix factorization (MF) and D-U-NET according to values of PSNR and SSIM for (0.1, 0.25, 0.5, and 0.75) levels of noise. The LDM achieved an inception score of 13.6 and an FID of 46.2 in the augmentation step.},
}
@article {pmid37956793,
year = {2024},
author = {Teo, KYC and Zhao, JZ and Klose, G and Lee, WK and Cheung, CMG},
title = {Polypoidal Choroidal Vasculopathy: Evaluation Based on 3-Dimensional Reconstruction of OCT Angiography.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {2},
pages = {98-107},
doi = {10.1016/j.oret.2023.11.001},
pmid = {37956793},
issn = {2468-6530},
mesh = {Humans ; *Choroid/pathology ; Polypoidal Choroidal Vasculopathy ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnosis/pathology ; },
abstract = {OBJECTIVE: Three-dimensional (3D) reconstruction using swept-source OCT angiography (SS-OCTA) can provide insights into the nature and structure of polypoidal choroidal vasculopathy (PCV) and its component parts, the polypoidal lesion (PL) and the branching neovascular network (BNN). This study aims to describe novel observations of PCV using 3D reconstruction of SS-OCTA, and to compare these observations with similar images of type I macular neovascularization (MNV) typical neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Clinical case series.<br><br>SUBJECTS: Patients with PCV in either eye from clinical studies conducted in a tertiary retina center.<br><br>METHODS: Images with prespecified SS-OCTA imaging protocol were obtained and reconstructed in 3D. Forty neovascularization lesions (30 PCV and 10 typical nAMD) based on SS-OCTA were analyzed.<br><br>MAIN OUTCOME MEASURES: The following 3 specific features were evaluated: (1) the pattern of flow signal within the PLs as either homogenous or showing internal vascular architecture; (2) the configuration of the BNN as hypermature, mature, or immature; and (3) the spatial arrangement of the PLs in relation to the BNN. Comparisons were made between PCV and typical nAMD.<br><br>RESULTS: All PLs exhibited internal vascular architecture in the form of coil-like loops and none exhibited homogenous flow. Small focal nodules were present within this internal vascular architecture in 70% of PLs. Branching neovascular networks exhibited a hypermature/mature configuration (100 vs. 50%, P < 0.01) and were associated with thicker choroid compared with typical nAMD type 1 MNV (238.7 &#xb1; 104.3 vs. 155.6 &#xb1; 49.2, P&#xa0;= 0.02). The BNN and PL were located at distinct anteroposterior planes in 81% of the eyes.<br><br>CONCLUSIONS: We identified proliferating vasculature in both the PL and the BNN. Comparison of the configuration suggests that the BNN represents a more chronic and inactive lesion than the PL.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37956321,
year = {2023},
author = {Weng, CY and Singh, RP and Gillies, MC and Regillo, CD},
title = {Optimizing Visual Outcomes in Patients With Neovascular Age-Related Macular Degeneration: the Potential Value of Sustained Anti-VEGF Therapy.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {11},
pages = {654-659},
doi = {10.3928/23258160-20231016-01},
pmid = {37956321},
issn = {2325-8179},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; *Choroidal Neovascularization/drug therapy ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Ranibizumab/therapeutic use ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {Neovascular age-related macular degeneration (nAMD) leads to irreversible central vision loss if untreated. Frequent administration of anti-vascular endothelial growth factor (anti-VEGF) injections inhibits disease activity with excellent functional and morphological benefits. However, these injections pose a heavy therapeutic burden, and treatment discontinuation is common. Although current anti-VEGF treatment paradigms, such as treat-and-extend, mitigate treatment burden while still leading to acceptable vision outcomes, they fail to sustain initial vision gains for many. Novel longer-acting anti-VEGF therapies may reduce the overall burden on nAMD patients. Gene therapy might offer a paradigm shift by providing continuous expression of anti-VEGF, potentially decreasing treatment requirements and improving long-term vision outcomes. [Ophthalmic Surg Lasers Imaging Retina 2023;54:654-659.].},
}
@article {pmid37954579,
year = {2023},
author = {Gerogianni, A and Baas, LM and Sjöström, DJ and van de Kar, NCAJ and Pullen, M and van de Peppel, SJ and Nilsson, PH and van den Heuvel, LP},
title = {Functional evaluation of complement factor I variants by immunoassays and SDS-PAGE.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1279612},
pmid = {37954579},
issn = {1664-3224},
mesh = {Humans ; *Complement Factor I/genetics/metabolism ; *Complement C3b/metabolism ; Mutation ; Enzyme-Linked Immunosorbent Assay ; Electrophoresis, Polyacrylamide Gel ; },
abstract = {Factor I (FI) is an essential regulator of the complement system. Together with co-factors, FI degrades C3b, which inhibits further complement activation. Genetic mutations in FI are associated with pathological conditions like age-related macular degeneration and atypical hemolytic uremic syndome. Here, we evaluated eight recombinant FI genetic variants found in patients. We assessed FI's co-factor activity in the presence of two co-factors; Factor H and soluble CR1. Different analytical assays were employed; SDS-PAGE to evaluate the degradation of C3b, ELISA to measure the generation of fluid phase iC3b and the degradation of surface-bound C3b using a novel Luminex bead-based assay. We demonstrate that mutations in the FIMAC and SP domains of FI led to significantly reduced protease activity, whereas the two analyzed mutations in the LDLRA2 domain did not result in any profound changes in FI's function. The different assays employed displayed a strong positive correlation, but differences in the activity of the genetic variants Ile55Phe and Gly261Asp could only be observed by combining different methods and co-factors for evaluating FI activity. In conclusion, our results provide a new perspective regarding available diagnostic tools for assessing the impact of mutations in FI.},
}
@article {pmid37954554,
year = {2023},
author = {Klaas, JE and Bui, V and Maierhofer, N and Schworm, B and Maier, M and Priglinger, SG and Siedlecki, J},
title = {Risk of transient vision loss after intravitreal aflibercept using vial-prepared vs. the novel prefilled syringe formulation.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1295633},
pmid = {37954554},
issn = {2296-858X},
abstract = {PURPOSE: To compare the risk of transient vision loss (TVL) probably attributable to a severe intraocular pressure spike after intravitreal aflibercept application using the novel prefilled syringe (PFS) vs. the established vial system (VS).<br><br>METHODS: Datasets of the intravitreal injection service of the Ludwig Maximilians-University Munich and the Technical University Munich, Germany, were screened for documentation of TVL after intravitreal injection of aflibercept. The observation period included two full months prior to the introduction of the novel PFS and two months afterwards. TVL was defined as loss of perception of hand motion for a duration of >30&#x2009;s.<br><br>RESULTS: Over a period of four months, 1720 intravitreal injections of aflibercept were administered in 672 patients. There were 842 injections with the old VS, and 878 injections using the novel PFS. Using the VS, TVL was noted during two injections (0.24%) in two patients, as compared to 11 cases of TVL (1.25%) in 10 patients with the PFS (p&#x2009;=&#x2009;0.015). Using the PFS, patients had a 5.3-fold risk of TVL as compared to the VS (OR: 5.33; 95% CI: 1.2-24.1; p&#x2009;=&#x2009;0.0298).<br><br>CONCLUSION: There was a more than five-fold risk of TVL using the novel pre-filled aflibercept syringe as compared to the established vial system. During informed consent, this risk should be discussed.},
}
@article {pmid37953589,
year = {2023},
author = {Ercan, &#xc7; and Elbay, A and Aslan, ES and Akbaş, F and Ozdemir, H and Ozgentürk, NO},
title = {MicroRNA-626 inhibits mTOR pathways activity of retinal pigment epithelial cells by targeting SLC7A5 in human ARPE-19 Cells.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {69},
number = {10},
pages = {17-22},
doi = {10.14715/cmb/2023.69.10.3},
pmid = {37953589},
issn = {1165-158X},
mesh = {Humans ; Epithelial Cells/metabolism ; *Large Neutral Amino Acid-Transporter 1/metabolism ; *Macular Degeneration/metabolism ; *MicroRNAs/metabolism ; Retinal Pigment Epithelium/metabolism ; Retinal Pigments/metabolism ; RNA, Small Interfering/metabolism ; TOR Serine-Threonine Kinases/genetics/metabolism ; },
abstract = {Recent studies have shown that miRNAs are associated with the pathological process involved in age-related macular degeneration (AMD). However, the microRNA-mediated post-transcriptional regulation in human retinal pigment epithelium (RPE) cells has not been adequately investigated. We investigated how miR-626 inhibits mTOR activity pathways and pathway-related genes in retinal pigment epithelial cells by targeting the solute carrier family seven-member 5 (SLC7A5) in ARPE19 cells. We transfected mir-626 mimic, mir-626 inhibitör and siRNA in human retinal pigment epithelial cell line was examined using RT-PCR and western blot, respectively. We knocked down mir-626 levels and overexpression by mir-626-siRNA transfection of human RPE cell lines, and using an MTT assay, we assessed the role of SLC7A5 on RPE cell proliferation. We additionally measured the expression of mTOR, Akt1, caspase 3, Bax, SLC17A7, SLC17A8, Creb1, Pten, HIF1A, HIFI. The findings demonstrate that mir-626 inhibits SLC7A5 gene expression and proliferation of ARPE-19 cells. Short interfering RNA (siRNA) mediated suppression of SLC7A5, a predicted target of mir-626, has the same effect on ARPE-19 cells. We identified how miR-626 causes apoptosis and macula degeneration in RPE cells by targeting SLC7A5 through the mTOR signaling pathway. miR-626 was an essential regulator of the expression of the Slc7a5 gene. Importantly, we determined that miR-626 is essential to play a role in AMD. This research project shows that SLC7A5 is a direct target of mir-626 in ARPE-19 cells for the first time.},
}
@article {pmid37953270,
year = {2023},
author = {Zhou, D and Hu, Y and Qiu, Z and Liu, Z and Jiang, H and Kawasaki, R and Liu, J},
title = {Retinal layers changes in patients with age-related macular degeneration treated with intravitreal anti-VEGF agents.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {451},
pmid = {37953270},
issn = {1471-2415},
support = {82102189//National Natural Science Foundation of China/ ; 2021A1515012195//Guangdong Basic and Applied Basic Research Foundation/ ; 20220815111736001//Shenzhen Stable Support Plan Program/ ; 2020ZDZX3043//Guangdong Provincial Department of Education/ ; },
mesh = {Humans ; *Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retina ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Tomography, Optical Coherence ; Retrospective Studies ; },
abstract = {BACKGROUND: The purpose of this study was to investigate retinal layers changes in patients with age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and to evaluate if these changes may affect treatment response.<br><br>METHODS: This study included 496 patients with AMD or PCV who were treated with anti-VEGF agents and followed up for at least 6&#xa0;months. A comprehensive analysis of retinal layers affecting visual acuity was conducted. To eliminate the fact that the average thickness calculated may lead to differences tending to converge towards the mean, we proposed that the retinal layer was divided into different regions and the thickness of the retinal layer was analyzed at the same time. The labeled data will be publicly available for further research.<br><br>RESULTS: Compared to baseline, significant improvement in visual acuity was observed in patients at the 6-month follow-up. Statistically significant reduction in central retinal thickness and separate retinal layer thickness was also observed (p&#x2009;<&#x2009;0.05). Among all retinal layers, the thickness of the external limiting membrane to retinal pigment epithelium/Bruch's membrane (ELM to RPE/BrM) showed the greatest reduction. Furthermore, the subregional assessment revealed that the ELM to RPE/BrM decreased greater than that of other layers in each region.<br><br>CONCLUSION: Treatment with anti-VEGF agents effectively reduced retinal thickness in all separate retinal layers as well as the retina as a whole and anti-VEGF treatment may be more targeted at the edema site. These findings could have implications for the development of more precise and targeted therapies for AMD treatment.},
}
@article {pmid37952011,
year = {2023},
author = {Tejero, JG and Neila, PM and Kurmann, T and Gallardo, M and Zinkernagel, M and Wolf, S and Sznitman, R},
title = {Predicting OCT biological marker localization from weak annotations.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {19667},
pmid = {37952011},
issn = {2045-2322},
mesh = {Humans ; *Diabetic Retinopathy/diagnostic imaging ; *Macular Edema/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging ; Biomarkers ; },
abstract = {Recent developments in deep learning have shown success in accurately predicting the location of biological markers in Optical Coherence Tomography (OCT) volumes of patients with Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR). We propose a method that automatically locates biological markers to the Early Treatment Diabetic Retinopathy Study (ETDRS) rings, only requiring B-scan-level presence annotations. We trained a neural network using 22,723 OCT B-Scans of 460 eyes (433 patients) with AMD and DR, annotated with slice-level labels for Intraretinal Fluid (IRF) and Subretinal Fluid (SRF). The neural network outputs were mapped into the corresponding ETDRS rings. We incorporated the class annotations and domain knowledge into a loss function to constrain the output with biologically plausible solutions. The method was tested on a set of OCT volumes with 322 eyes (189 patients) with Diabetic Macular Edema, with slice-level SRF and IRF presence annotations for the ETDRS rings. Our method accurately predicted the presence of IRF and SRF in each ETDRS ring, outperforming previous baselines even in the most challenging scenarios. Our model was also successfully applied to en-face marker segmentation and showed consistency within C-scans, despite not incorporating volume information in the training process. We achieved a correlation coefficient of 0.946 for the prediction of the IRF area.},
}
@article {pmid37951481,
year = {2023},
author = {Gacche, RN},
title = {Changing landscape of anti-angiogenic therapy: Novel approaches and clinical perspectives.},
journal = {Biochimica et biophysica acta. Reviews on cancer},
volume = {1878},
number = {6},
pages = {189020},
doi = {10.1016/j.bbcan.2023.189020},
pmid = {37951481},
issn = {1879-2561},
mesh = {Humans ; *Angiogenesis Inhibitors/pharmacology/therapeutic use ; *Neoplasms/drug therapy/blood supply ; Immunotherapy ; Combined Modality Therapy ; Treatment Outcome ; },
abstract = {Targeting angiogenesis has remained one of the important aspects in disease biology in general and cancer in particular. Currently (June 2023), over 593 clinical trials have been registered at ClinicalTrials.gov having inference of term 'angiogenesis'. A panel of 14 anti-angiogenic drugs have been approved by FDA for the treatment of variety of cancers and other human ailments. Although the anti-angiogenic therapy (AAT) has gained significant clinical attention as a promising approach in the treatment of various diseases, particularly cancer, however, sizable literature has accumulated in the recent past describing the aggressive nature of tumours after the drug holidays, evolving drug resistance and off-target toxicities. Nevertheless, the emergence of inscrutable compensatory or alternative angiogenic mechanisms is limiting the efficacy of anti-angiogenic drugs and focussing the therapeutic regime as a puzzle of 'Lernaean hydra'. This review offers an overview of recent updates on the efficacy of antiangiogenic therapy and the current clinical performance of aaRTK inhibitors. Additionally, it also explores the changing application landscape of AAT, focusing on its role in diabetic nephropathy, age-related macular degeneration and other neovascular ocular disorders. Combination therapy with antiangiogenic drugs and immune check point inhibitors (ICIs) has emerged as a potential strategy to enhance the therapeutic index of cancer immunotherapy. While clinical studies have demonstrated the clinical efficacy of this approach, they also highlight the complex and sometimes unpredictable adverse events associated with it. Normalizing tumour vasculature has been identified as a key factor in unlocking the full potential of ICIs, thereby providing hope for improved treatment outcomes. The future prospects and challenges of AAT have been described with special reference to integration of technological advances for enhancing its efficacy and applications beyond its discovery.},
}
@article {pmid37951353,
year = {2023},
author = {Yuan, PH and Khan, HM and Sumita, FAG and Ribeiro Monteiro, ML and Preti, RC and Navajas, EV},
title = {Brolucizumab after failure of aflibercept with photodynamic therapy in polypoidal choroidal vasculopathy: A case report.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {98},
number = {12},
pages = {713-717},
doi = {10.1016/j.oftale.2023.10.009},
pmid = {37951353},
issn = {2173-5794},
mesh = {Humans ; *Choroid Diseases/drug therapy/complications ; Polypoidal Choroidal Vasculopathy ; *Photochemotherapy ; },
abstract = {We describe one case of polypoidal choroidal vasculopathy with persistent subretinal fluid despite multiple treatment with intravitreal Bevacizumab, Ranibizumab and Aflibercept, as well as Aflibercept associated with photodynamic therapy. The patient reached complete resolution after intravitreal Brolucizumab injection, but experienced recurrence of subretinal fluid 12 weeks after discontinuation. Brolucizumab might be an option in treating subretinal fluid after failure of other anti-VEGF agents associated with photodynamic therapy.},
}
@article {pmid37947908,
year = {2024},
author = {Torimura, A and Kanei, S and Shimizu, Y and Baba, T and Uotani, R and Sasaki, SI and Nagase, D and Inoue, Y and Ochiya, T and Miyazaki, D},
title = {Profiling miRNAs in tear extracellular vesicles: a pilot study with implications for diagnosis of ocular diseases.},
journal = {Japanese journal of ophthalmology},
volume = {68},
number = {1},
pages = {70-81},
pmid = {37947908},
issn = {1613-2246},
support = {23K15931//ministry of education, science, and culture/ ; },
mesh = {Humans ; *MicroRNAs/genetics/metabolism ; Pilot Projects ; *Diabetic Retinopathy/diagnosis/genetics/metabolism ; Cross-Sectional Studies ; *Macular Edema ; *Extracellular Vesicles/genetics/metabolism ; },
abstract = {PURPOSE: To estimate the roles of extracellular vesicles (EVs) in tears and to determine whether their profiles are associated with the type of ocular disease.<br><br>STUDY DESIGN: Cross-sectional study.<br><br>METHODS: Tear EVs were extracted from 14 healthy participants and from 21 patients with retinal diseases (age-related macular degeneration [AMD] or diabetic macular edema [DME]). The surface marker expression of tear EVs was examined, and microRNAs (miRNAs) were extracted and profiled by use of real-time PCR array. The stability of the expression of the miRNAs was determined, and their functions were assessed by network analyses. Classification accuracy was evaluated by use of a random forest classifier and k-fold cross-validation.<br><br>RESULTS: The miRNAs that were highly expressed in tear EVs were miR-323-3p, miR-548a-3p, and miR-516a-5p. The most stably expressed miRNAs independent of diseases were miR-520h and miR-146b-3p. The primary networks of the highly stably expressed endogenous miRNAs were annotated as regulation of organismal injury and abnormalities. The highly expressed miRNAs for severe retinal disease were miR-151-5p for AMD and miR-422a for DME, suggesting potential roles of tear EVs in liquid biopsy. Nine miRNAs (miR-25, miR-30d, miR-125b, miR-132, miR-150, miR-184, miR-342-3p, miR-378, and miR-518b) were identified as distinguishing individuals with AMD from healthy individuals with a classification accuracy of 91.9%.<br><br>CONCLUSIONS: The finding that tear EVs contain characteristic miRNA species indicates that they may help in maintaining homeostasis and serve as a potential tool for disease diagnosis.},
}
@article {pmid37947776,
year = {2023},
author = {Honzíková, T and Agbaga, MP and Anderson, RE and Brush, R and Ahmad, M and Musílková, L and Šejstalová, K and Alishevich, K and Beneš, R and Šimicová, P and Berčíková, M and Filip, V and Kyselka, J},
title = {Novel Approaches for Elongation of Fish Oils into Very-Long-Chain Polyunsaturated Fatty Acids and Their Enzymatic Interesterification into Glycerolipids.},
journal = {Journal of agricultural and food chemistry},
volume = {71},
number = {46},
pages = {17909-17923},
pmid = {37947776},
issn = {1520-5118},
mesh = {Fatty Acids, Unsaturated/chemistry ; *Membrane Proteins/genetics ; Retina ; Humans ; *Fish Oils/analysis ; Male ; Fatty Acids/analysis ; Semen ; Animals ; Macular Degeneration/congenital ; },
abstract = {Elongation of the Very-Long-Chain Fatty Acids-4 (ELOVL4) enzyme that is expressed in neuronal tissues, sperm, and testes mediates biosynthesis of very-long-chain polyunsaturated fatty acids (VLC-PUFAs) from dietary long chain PUFAs (LC-PUFAs). The VLC-PUFAs are critical for neuronal and reproductive function. Therefore, mutations in ELOVL4 that affect VLC-PUFA biosynthesis contribute to retinal degenerative diseases including Autosomal Dominant Stargardt-like Macular Dystrophy (STGD3). Recent studies have also shown not only a depletion of retinal VLC-PUFAs with normal aging but also a more significant loss of VLC-PUFAs in donor eyes of patients with age-related macular degeneration (AMD). However, currently, there are no natural sources of VLC-PUFAs to be evaluated as dietary supplements for the attenuation of retinal degeneration in animal models of STGD3. Here, we report the development of a novel chemical approach for elongation of eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids from fish oils by 6 carbon atoms to make a unique group of VLC-PUFAs, namely all-cis-hexacosa-11,14,17,20,23-pentaenoic acids (C26:5 n-3) and all-cis-octacosa-10,13,16,19,22,25-hexaenoic acids (C28:6 n-3). The three-step elongation approach that we report herein resulted in a good overall yield of up to 20.2%. This more sustainable approach also resulted in improved functional group compatibility and minimal impact on the geometrical integrity of the all-cis double bond system of the VLC-PUFAs. In addition, we also successfully used commercial deep-sea fish oil concentrate as an inexpensive material for the C6 elongation of fish oil LC-PUFAs into VLC-PUFAs, which resulted in the making of gram scales of VLC-PUFAs with an even higher isolation yield of 31.0%. The quality of fish oils and the content of oxidized lipids were key since both strongly affected the activity of the PEPPSI-IPr catalyst and ultimately the yield of coupling reactions. Downstream enzymatic interesterification was used for the first time to prepare structured glycerolipids enriched with VLC-PUFAs that could be evaluated in vivo to determine absorption and transport to target tissues relative to those of the free fatty acid forms. It turned out that in the synthesis of structured triacylglycerols and glycerophospholipids with VLC-PUFAs, the polarity of the immobilized lipase carrier and its humidity were essential.},
}
@article {pmid37945975,
year = {2023},
author = {Hikichi, T},
title = {Correction to: Investigation of satisfaction with short‑term outcomes after switching to faricimab to treat neovascular age‑related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {6},
pages = {657},
doi = {10.1007/s10384-023-01035-1},
pmid = {37945975},
issn = {1613-2246},
}
@article {pmid37945766,
year = {2023},
author = {Riazi-Esfahani, H and Asadi Khameneh, E and Ghassemi, F and Mehrabi Bahar, M and Torkashvand, A and Mahmoudi, A and Husein Ahmed, A and Faghihi, S and Rahimi, M and Akbarzadeh, A and Faghihi, H and Khalili Pour, E},
title = {Pachychoroid neovasculopathy versus macular neovascularization in age-related macular degeneration with and without shallow irregular pigment epithelial detachment.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {19513},
pmid = {37945766},
issn = {2045-2322},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/drug therapy ; *Retinal Detachment/diagnostic imaging ; Choroid/blood supply ; *Choroidal Neovascularization/diagnostic imaging/drug therapy ; Angiography ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Fluorescein Angiography/methods ; *Wet Macular Degeneration ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {To compare the choroidal neovascular features of individuals with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD) with and without shallow irregular pigment epithelial detachment (SIPED). Using optical coherence tomography angiography, the choroidal neovascular complexes of 27 patients with PNV, 34 patients with nAMD and SIPED, and 15 patients with nAMD without SIPED were analyzed with FIJI and AngioTool software. PNV compared to nAMD with SIPED had a greater vessel percentage area (P = 0.034), junction density (P = 0.045), average vessel length (P < 0.001), and fractal dimension (P < 0.001). PNV, compared to nAMD without SIPED, had a greater total vessel length (P = 0.002), total number of junctions (P < 0.001), junction density (P = 0.034), and fractal dimension (P = 0.005). nAMD with SIPED, compared to nAMD without SIPED, had greater vessel area, total number of junctions, total vessel length, and average vessel length (all P values < 0.001). Patients with nAMD plus SIPED and individuals with nAMD without SIPED have similar fractal dimension values (P = 0.703). Biomarkers of choroidal neovascular complexity, such as fractal dimension, can be used to differentiate PNV from nAMD with or without SIPED.},
}
@article {pmid37945665,
year = {2023},
author = {Leingang, O and Riedl, S and Mai, J and Reiter, GS and Faustmann, G and Fuchs, P and Scholl, HPN and Sivaprasad, S and Rueckert, D and Lotery, A and Schmidt-Erfurth, U and Bogunović, H},
title = {Automated deep learning-based AMD detection and staging in real-world OCT datasets (PINNACLE study report 5).},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {19545},
pmid = {37945665},
issn = {2045-2322},
support = {210572/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 10572/Z/18/Z./WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Deep Learning ; Tomography, Optical Coherence/methods ; Retrospective Studies ; *Macular Degeneration/diagnostic imaging ; Neural Networks, Computer ; },
abstract = {Real-world retinal optical coherence tomography (OCT) scans are available in abundance in primary and secondary eye care centres. They contain a wealth of information to be analyzed in retrospective studies. The associated electronic health records alone are often not enough to generate a high-quality dataset for clinical, statistical, and machine learning analysis. We have developed a deep learning-based age-related macular degeneration (AMD) stage classifier, to efficiently identify the first onset of early/intermediate (iAMD), atrophic (GA), and neovascular (nAMD) stage of AMD in retrospective data. We trained a two-stage convolutional neural network to classify macula-centered 3D volumes from Topcon OCT images into 4 classes: Normal, iAMD, GA and nAMD. In the first stage, a 2D ResNet50 is trained to identify the disease categories on the individual OCT B-scans while in the second stage, four smaller models (ResNets) use the concatenated B-scan-wise output from the first stage to classify the entire OCT volume. Classification uncertainty estimates are generated with Monte-Carlo dropout at inference time. The model was trained on a real-world OCT dataset, 3765 scans of 1849 eyes, and extensively evaluated, where it reached an average ROC-AUC of 0.94 in a real-world test set.},
}
@article {pmid37943552,
year = {2023},
author = {Berlin, A and Messinger, JD and Balaratnasingam, C and Mendis, R and Ferrara, D and Freund, KB and Curcio, CA},
title = {Imaging Histology Correlations of Intraretinal Fluid in Neovascular Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {11},
pages = {13},
pmid = {37943552},
issn = {2164-2591},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY006109/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Endothelial Growth Factors ; Subretinal Fluid ; Tomography, Optical Coherence ; Eye ; *Macular Degeneration/diagnosis ; },
abstract = {PURPOSE: Fluid presence and dynamism is central to the diagnosis and management of neovascular age-related macular degeneration. On optical coherence tomography (OCT), some hyporeflective spaces arise through vascular permeability (exudation) and others arise through degeneration (transudation). Herein we determined whether the histological appearance of fluid manifested this heterogeneity.<br><br>METHODS: Two eyes of a White woman in her 90s with anti-vascular endothelial growth factor treated bilateral type 3 neovascularization secondary to age-related macular degeneration were osmicated, prepared for submicrometer epoxy resin sections, and correlated to eye-tracked spectral domain OCT. Examples of intraretinal tissue fluid were sought among similarly prepared donor eyes with fibrovascular scars, in a web-based age-related macular degeneration histopathology resource. Fluid stain intensity was quantified in reference to Bruch's membrane and the empty glass slide.<br><br>RESULTS: Exudative fluid by OCT was slightly reflective and dynamically responded to anti-vascular endothelial growth factor. On histology, this fluid stained moderately, possessed a smooth and homogenous texture, and contained blood cells and fibrin. Nonexudative fluid in degenerative cysts and in outer retinal tubulation was minimally reflective on OCT and did not respond to anti-vascular endothelial growth factor. By histology, this fluid stained lightly, possessed a finely granular texture, and contained mainly tissue debris. Quantification supported the qualitative impressions of fluid stain density. Cells containing retinal pigment epithelium organelles localized to both fluid types.<br><br>CONCLUSIONS: High-resolution histology of osmicated tissue can distinguish between exudative and nonexudative fluid, some of which is transudative.<br><br>TRANSLATIONAL RELEVANCE: OCT and histological features of different fluid types can inform clinical decision-making and assist in the interpretation of newly available automated fluid detection algorithms.},
}
@article {pmid37942735,
year = {2023},
author = {Cai, YH and Huang, X},
title = {Abnormal functional connectivity strength in age-related macular degeneration patients: a fMRI study.},
journal = {Neuroreport},
volume = {34},
number = {18},
pages = {845-852},
doi = {10.1097/WNR.0000000000001962},
pmid = {37942735},
issn = {1473-558X},
mesh = {Humans ; Magnetic Resonance Imaging/methods ; Brain/diagnostic imaging ; Parietal Lobe ; *Motor Cortex ; *Macular Degeneration/diagnostic imaging ; },
abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a serious blinding eye disease. Previous neuroimaging studies reported that AMD were accompanied by abnormalities of the brain. However, whether AMD patients were associated with functional connectivity strength (FCS) or not remains unknown. In our study, the purpose of the study was to assess FCS changes in AMD patients.<br><br>METHODS: In our study, 20 AMD patients and 20 healthy controls (HCs), matched closely by sex, age, and educational level were underwent MRI scanning. FCS method and seed-based functional connectivity (FC) method were applied to investigate the functional network changes between two groups. Moreover, support vector machine (SVM) method was applied to assess the FCS maps as a feature to classification of AMD diseases.<br><br>RESULTS: Our study reported that AMD patients showed decreased FCS values in the bilateral calcarine, left supplementary motor area, left superior parietal lobule and left paracentral lobule (ParaL) relative to the HC group. Meanwhile, our study found that the AMD patients showed abnormal FC within visual network, sensorimotor network and default mode network. Moreover, the SVM method showed that FCS maps as machine learning features shows good classification efficiency (area under curve&#x2005;=&#x2005;0.82) in the study.<br><br>CONCLUSION: Our study demonstrated that AMD patients showed abnormal FCS with the visual network, sensorimotor network and default mode network, which might reflect the impaired vision, cognition and motor function in AMD patients. In addition, FCS indicator can be used as an effective biological marker to assist the clinical diagnosis of AMD.},
}
@article {pmid37942596,
year = {2023},
author = {Fursova, AZ and Nikulich, IF and Dmitrieva, EI and Gusarevich, OG and Derbeneva, AS and Vasilyeva, MA and Kozhevnikova, OS and Kolosova, NG},
title = {[Three-year follow-up study of clinical effectiveness of antiangiogenic therapy for neovascular age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {5},
pages = {45-52},
doi = {10.17116/oftalma202313905145},
pmid = {37942596},
issn = {0042-465X},
mesh = {Humans ; Follow-Up Studies ; Ranibizumab/therapeutic use ; Prospective Studies ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; Visual Acuity ; Angiogenesis Inhibitors/therapeutic use ; Treatment Outcome ; *Macular Degeneration/diagnosis/drug therapy ; Atrophy ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: The study analyzes long-term (three years) clinical effectiveness of anti-VEGF treatment of neovascular age-related macular degeneration (nAMD) and attempts to identify the most clinically significant associations between the functional and structural parameters.<br><br>MATERIAL AND METHODS: The study included 122 patients (122 eyes) diagnosed with nAMD, mean age -73.4&#xb1;6.6 years old. Prospective follow-up lasted 144 weeks. All patients were treated with angiogenesis inhibitor (aflibercept 2 mg), and most of them (72.9%) - according to the Treat-and-Extend protocol.<br><br>RESULTS: The average number of injections was 7.39&#xb1;1.28, 4.63&#xb1;0.97 and 4.06&#xb1;0.81 during the first, second and third years of the follow-up, respectively. The mean baseline best-corrected visual acuity (BCVA) was 0.24&#xb1;0.21. After three loading doses, BCVA increased to 0.33&#xb1;0.26 (+0.09; 37.5%), by the end of follow-up BCVA was 0.35&#xb1;0.27 (+0.11; 45.8%). Central retinal thickness (CRT) decreased from 314.89&#xb1;88.07 &#x3bc;m to 234.4&#xb1;42.8 &#x3bc;m (a 25.5% decrease) by the end of the follow-up. After three loading injections baseline functional and anatomical parameters had the most significant correlations (r&#x2265;0.7, p<0.05) with intraretinal fluid, ellipsoid zone integrity and the area of macular atrophy.<br><br>CONCLUSIONS: Analysis of the morphological and functional outcomes by the end of the first year demonstrates the feasibility of preserving the results while reducing the number of visits and injections according to the Treat-and-Extend protocol. Achieving maximum improvement of functional parameters most significantly correlated with changes in such biomarkers as central retinal thickness, area of macular atrophy and integrity of the ellipsoid zone.},
}
@article {pmid37940659,
year = {2023},
author = {Nielsen, MK and Subhi, Y and Falk, M and Singh, A and Sørensen, TL and Nissen, MH and Faber, C},
title = {Complement factor H Y402H polymorphism results in diminishing CD4[+] T cells and increasing C-reactive protein in plasma.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {19414},
pmid = {37940659},
issn = {2045-2322},
mesh = {Aged ; Mice ; Animals ; Humans ; *C-Reactive Protein/metabolism ; Complement Factor H/genetics/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Angiogenesis Inhibitors ; Polymorphism, Single Nucleotide ; Mice, Inbred C57BL ; Visual Acuity ; Vascular Endothelial Growth Factor A/genetics ; *Wet Macular Degeneration ; Genotype ; CD4-Positive T-Lymphocytes/metabolism ; Case-Control Studies ; },
abstract = {Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4[+] and CD8[+] T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4[+] and CD8[+] T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4[+] T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4[+] T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4[+] T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4[+] T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4[+] cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4[+] T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.},
}
@article {pmid37940612,
year = {2024},
author = {Chobisa, D and Muniyandi, A and Sishtla, K and Corson, TW and Yeo, Y},
title = {Long-Acting Microparticle Formulation of Griseofulvin for Ocular Neovascularization Therapy.},
journal = {Small (Weinheim an der Bergstrasse, Germany)},
volume = {20},
number = {10},
pages = {e2306479},
pmid = {37940612},
issn = {1613-6829},
support = {R01 EY025641/EY/NEI NIH HHS/United States ; R01 EY035159/EY/NEI NIH HHS/United States ; R01EY025641/NH/NIH HHS/United States ; R01EY035159/NH/NIH HHS/United States ; },
mesh = {Mice ; Humans ; Animals ; Aged ; Polylactic Acid-Polyglycolic Acid Copolymer ; *Griseofulvin/pharmacology/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; Endothelial Cells/metabolism ; *Choroidal Neovascularization/drug therapy/metabolism/prevention &amp; control ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults. nAMD is treated with biologics targeting vascular endothelial growth factor; however, many patients do not respond to the current therapy. Here, a small molecule drug, griseofulvin (GRF), is used due to its inhibitory effect on ferrochelatase, an enzyme important for choroidal neovascularization (CNV). For local and sustained delivery to the eyes, GRF is encapsulated in microparticles based on poly(lactide-co-glycolide) (PLGA), a biodegradable polymer with a track record in long-acting formulations. The GRF-loaded PLGA microparticles (GRF MPs) are designed for intravitreal application, considering constraints in size, drug loading content, and drug release kinetics. Magnesium hydroxide is co-encapsulated to enable sustained GRF release over >30 days in phosphate-buffered saline with Tween 80. Incubated in cell culture medium over 30 days, the GRF MPs and the released drug show antiangiogenic effects in retinal endothelial cells. A single intravitreal injection of MPs containing 0.18 µg GRF releases the drug over 6 weeks in vivo to inhibit the progression of laser-induced CNV in mice with no abnormality in the fundus and retina. Intravitreally administered GRF MPs prove effective in preventing CNV, providing proof-of-concept toward a novel, cost-effective nAMD therapy.},
}
@article {pmid37939831,
year = {2024},
author = {Fan, X and Yang, Y and Wu, G and Kong, Y and Zhang, Y and Zha, X},
title = {Circ-CARD6 inhibits oxidative stress-induced apoptosis and autophagy in ARPE-19 cells via the miR-29b-3p/PRDX6/PI3K/Akt axis.},
journal = {Experimental eye research},
volume = {238},
number = {},
pages = {109690},
doi = {10.1016/j.exer.2023.109690},
pmid = {37939831},
issn = {1096-0007},
mesh = {Humans ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Reactive Oxygen Species ; Hydrogen Peroxide ; Autophagy ; Apoptosis ; Oxidative Stress ; *Macular Degeneration/genetics ; *MicroRNAs/genetics ; Cell Proliferation ; CARD Signaling Adaptor Proteins ; Peroxiredoxin VI ; },
abstract = {BACKGROUND: Oxidative stress-induced damage and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD) and hereditary retinopathy diseases (HRDs). This study aimed to elucidate the roles and mechanisms of circ-CARD6 and miR-29b-3p in oxidative stress-induced RPE and provide new ideas for the diagnosis and treatment of retinopathy disease (RD).<br><br>METHODS: A model of oxidative stress-induced RPE (ARPE-19) was established, and the level of malondialdehyde (MDA) and concentration of reactive oxygen species (ROS) were detected by a DCFH-DA fluorescent probe and MDA kit. The cell viability was measured by a CCK-8 assay. The expression of PRDX6/PI3K/Akt axis genes and proteins related to apoptosis and autophagy were determined by RT&#x2012;qPCR and Western blot analyses. The dual-luciferase reporter system confirmed the targeting relationship between miR-29b-3p and circ-CARD6 and between miR-29b-3p and PRDX6.<br><br>RESULTS: In H2O2-treated ARPE-19&#xa0;cells, the expression of circ-CARD6 and PRDX6 was decreased, while the expression of miR-29b-3p was increased. The overexpression of circ-CARD6 inhibits oxidative stress-induced increases in ROS, apoptosis and autophagy in ARPE-19&#xa0;cells. circ-CARD6 targets miR-29b-3p, miR-29b-3p targets PRDX6, and circ-CARD6 regulates PRDX6 via miR-29b-3p. Further studies showed that circ-CARD6 acts as a competitive endogenous RNA of miR-29b-3p to affect the expression of PRDX6, thereby inhibiting autophagy and apoptosis in ARPE-19&#xa0;cells.<br><br>CONCLUSION: circ-CARD6 can inhibit oxidative stress and apoptosis by regulating the miR-29b-3p/PRDX6/PI3K/Akt axis.},
}
@article {pmid37937806,
year = {2024},
author = {Emamverdi, M and Habibi, A and Ashrafkhorasani, M and Nittala, MG and Kadomoto, S and Sadda, SR},
title = {Optical Coherence Tomography Features of Macular Hyperpigmented Lesions without Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration.},
journal = {Current eye research},
volume = {49},
number = {1},
pages = {73-79},
doi = {10.1080/02713683.2023.2267801},
pmid = {37937806},
issn = {1460-2202},
support = {R01 EY023164/EY/NEI NIH HHS/United States ; R01 EY030614/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Fluorescein Angiography/methods ; *Macular Degeneration/pathology ; Retinal Pigment Epithelium/pathology ; *Hyperpigmentation/diagnosis/pathology ; },
abstract = {PURPOSE: To evaluate the optical coherence tomography (OCT) features of hyperpigmented lesions in the absence of intraretinal hyperreflective foci (IHRF) on OCT in eyes with age-related macular degeneration (AMD).<br><br>METHODS: We retrospectively analyzed OCT images of eyes with intermediate AMD (iAMD) and macular hyperpigmentation (HP) on color fundus photograph (CFP) but without IHRF on OCT in the corresponding location. The most prominent or definite HP was selected for analysis. The infrared reflectance (IR) image registered with the CFP, and the location corresponding to the HP lesion were defined on the IR image. The location of the HP on the corresponding OCT B-scan was assessed for retinal pigment epithelium (RPE) elevation, acquired vitelliform lesion (AVL), abnormal retinal pigment epithelium&#x2009;+&#x2009;basal lamina (RPE&#x2009;+&#x2009;BL) band reflectivity, RPE&#x2009;+&#x2009;BL band thickening, as well as interdigitation zone (IZ), ellipsoid zone (EZ) and external limiting membrane (ELM) disruption.<br><br>RESULTS: 49 eyes (39 patients) were included in this study. Forty-six (94%) of the hyperpigmented lesions showed a thickened RPE&#x2009;+&#x2009;BL band. RPE&#x2009;+&#x2009;BL band reflectivity was increased in 37 (76%) of the lesions. RPE&#x2009;+&#x2009;BL band thickening, however, was not correlated with RPE&#x2009;+&#x2009;BL band reflectivity (p-value = 0.31). Either thickening or hyperreflectivity of the RPE&#x2009;+&#x2009;BL band was present in all cases. Twenty (41%) lesions had evidence of ELM disruption, 42 (86%) demonstrated EZ disruption and 48 (98%) had IZ disruption. Five (10%) HPs demonstrated AVL. Among cases with RPE elevation (15 cases, 31%), 10 were classified as drusen, 2 as drusenoid PEDs, and 3 as fibrovascular PEDs.<br><br>CONCLUSIONS: Thickening and/or hyperreflectivity of the RPE&#x2009;+&#x2009;BL band commonly correspond to regions of macular hyperpigmentation without IHRF in eyes with iAMD.},
}
@article {pmid37936001,
year = {2023},
author = {Zeng, Y and Dong, W and Zhang, W and Deng, B},
title = {Association of NLRPs with pathogenesis of dry age-related macular degeneration.},
journal = {International ophthalmology},
volume = {43},
number = {12},
pages = {4869-4878},
pmid = {37936001},
issn = {1573-2630},
support = {ZYGX2018J098//the National University Basic funding/ ; 2017QN02//the Youth Scientific Research Fund of Sichuan Provincial People's Hospital/ ; 2021kflx007//the Scientific Research Project of Sichuan Provincial People's Hospital/ ; },
mesh = {Aged ; Humans ; *Geographic Atrophy/diagnosis ; Inflammation ; Leukocytes, Mononuclear ; Mitochondrial Proteins ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; *Wet Macular Degeneration/diagnosis/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and Dry AMD is the most common clinical subtype. However, effective measures for the early diagnosis and treatment of dry AMD have not been proposed. In recent years, NOD-like receptors (NLRs) have received attention in the study of AMD as an important class of pattern recognition receptors. We attempted to elucidate the pathogenesis of NLRs in dry AMD from the perspective of chronic inflammation.<br><br>METHODS: This study involved 13 patients with dry AMD, 10 age- and sex-matched normal population without any history of disease and 8 patients with wet AMD as controls. Using RT-qPCR, the mRNA expression levels of NLRs in peripheral blood peripheral blood mononuclear cells (PBMCs) were compared to analyze the statistical differences in the expression contents among the three populations.<br><br>RESULTS: The relative RNA expression of nucleotide-binding oligomerization-like receptor protein 12 (NLRP12) with negative regulation of inflammation was significantly lower in dry AMD patients than in normal people and wet AMD patients. And NLRX1, which also has an anti-inflammatory effect, was lower in dry AMD patients than in wet AMD patients. However, NLRP3 with proinflammatory effect was significantly expressed in wet AMD.<br><br>CONCLUSION: The significant decrease in NLRP12 in dry AMD may become a breakthrough in the study of dry AMD and systemic chronic inflammatory response. However, NLRP3 may have a more important role in wet AMD.},
}
@article {pmid37935821,
year = {2023},
author = {Fietz, A and Schnichels, S and Hurst, J},
title = {Co-cultivation of primary porcine RPE cells and neuroretina induces inflammation: a potential inflammatory AMD-model.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {19345},
pmid = {37935821},
issn = {2045-2322},
mesh = {Swine ; Animals ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/pathology ; Inflammation/pathology ; Cytokines/metabolism ; *Retinal Diseases/pathology ; },
abstract = {One common aspect in the pathology of many retinal diseases like age-related macular degeneration (AMD) is the death of retinal pigment epithelium (RPE) cells. RPE cells are essential for photoreceptor survival as they recycle and remove compounds of the visual cycle and secrete protective cytokines. Studying RPE cells is crucial to improve our understanding of retinal pathologies, yet only a few retinal ex vivo models include them or do so only indirectly. Besides the positive effects in indirect co-cultivation models, also a slight inflammation was observed. In this study we developed an ex vivo model consisting of a primary porcine RPE monolayer directly co-cultured with porcine retinal organ cultures, to investigate and simulate inflammatory retinal diseases, such as (dry) AMD. The direct co-cultivation resulted in immune reactivity (enhanced expression of pro-inflammatory cytokines e.g., IL-1β, IL-6, IL-8) and cell death. These effects were evaluated for the retinal explant as well as for the RPE-monolayer to further understand the complex interactions between these two compartments. Taken together, this ex vivo model can be used to study inflammatory retinal diseases like AMD as well as the rejection observed after RPE-transplantation.},
}
@article {pmid37934784,
year = {2024},
author = {Kwong, A and Zawistowski, M and Fritsche, LG and Zhan, X and Bragg-Gresham, J and Branham, KE and Advani, J and Othman, M and Ratnapriya, R and Teslovich, TM and Stambolian, D and Chew, EY and Abecasis, GR and Swaroop, A},
title = {Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration.},
journal = {Human molecular genetics},
volume = {33},
number = {4},
pages = {374-385},
pmid = {37934784},
issn = {1460-2083},
support = {R01 EY031209/EY/NEI NIH HHS/United States ; ZIAEY000546/EY/NEI NIH HHS/United States ; ZIA EY000489/ImNIH/Intramural NIH HHS/United States ; ZIA EY000546/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Genome-Wide Association Study/methods ; *Macular Degeneration/genetics ; Genotype ; Genetic Testing ; Whole Genome Sequencing ; Polymorphism, Single Nucleotide/genetics ; Genetic Predisposition to Disease ; Complement Factor H/genetics ; },
abstract = {Genome-wide association studies have contributed extensively to the discovery of disease-associated common variants. However, the genetic contribution to complex traits is still largely difficult to interpret. We report a genome-wide association study of 2394 cases and 2393 controls for age-related macular degeneration (AMD) via whole-genome sequencing, with 46.9 million genetic variants. Our study reveals significant single-variant association signals at four loci and independent gene-based signals in CFH, C2, C3, and NRTN. Using data from the Exome Aggregation Consortium (ExAC) for a gene-based test, we demonstrate an enrichment of predicted rare loss-of-function variants in CFH, CFI, and an as-yet unreported gene in AMD, ORMDL2. Our method of using a large variant list without individual-level genotypes as an external reference provides a flexible and convenient approach to leverage the publicly available variant datasets to augment the search for rare variant associations, which can explain additional disease risk in AMD.},
}
@article {pmid37934489,
year = {2023},
author = {Cupini, S and Di Marco, S and Boselli, L and Cavalli, A and Tarricone, G and Mastronardi, V and Castagnola, V and Colombo, E and Pompa, PP and Benfenati, F},
title = {Platinum Nanozymes Counteract Photoreceptor Degeneration and Retina Inflammation in a Light-Damage Model of Age-Related Macular Degeneration.},
journal = {ACS nano},
volume = {17},
number = {22},
pages = {22800-22820},
pmid = {37934489},
issn = {1936-086X},
mesh = {Humans ; Rats ; Animals ; Aged ; Platinum/pharmacology/therapeutic use ; Antioxidants/pharmacology ; *Metal Nanoparticles/therapeutic use ; Retina/metabolism ; *Retinal Degeneration/drug therapy/etiology/metabolism ; *Macular Degeneration/drug therapy ; Inflammation/drug therapy/complications ; Rats, Sprague-Dawley ; Light ; Disease Models, Animal ; },
abstract = {Degeneration of photoreceptors in age-related macular degeneration (AMD) is associated with oxidative stress due to the intense aerobic metabolism of rods and cones that if not properly counterbalanced by endogenous antioxidant mechanisms can precipitate photoreceptor degeneration. In spite of being a priority eye disease for its high incidence in the elderly, no effective treatments for AMD exist. While systemic administration of antioxidants has been unsuccessful in slowing down degeneration, locally administered rare-earth nanoparticles were shown to be effective in preventing retinal photo-oxidative damage. However, because of inherent problems of dispersion in biological media, limited antioxidant power, and short lifetimes, these NPs are still confined to the preclinical stage. Here we propose platinum nanoparticles (PtNPs), potent antioxidant nanozymes, as a therapeutic tool for AMD. PtNPs exhibit high catalytic activity at minimal concentrations and protect primary neurons against oxidative insults and the ensuing apoptosis. We tested the efficacy of intravitreally injected PtNPs in preventing or mitigating light damage produced in dark-reared albino Sprague-Dawley rats by in vivo electroretinography (ERG) and ex vivo retina morphology and electrophysiology. We found that both preventive and postlesional treatments with PtNPs increased the amplitude of ERG responses to light stimuli. Ex vivo recordings demonstrated the selective preservation of ON retinal ganglion cell responses to light stimulation in lesioned retinas treated with PtNPs. PtNPs administered after light damage significantly preserved the number of photoreceptors and inhibited the inflammatory response to degeneration, while the preventive treatment had a milder effect. The data indicate that PtNPs can effectively break the vicious cycle linking oxidative stress, degeneration, and inflammation by exerting antioxidant and anti-inflammatory actions. The increased photoreceptor survival and visual performances in degenerated retinas, together with their high biocompatibility, make PtNPs a potential strategy to cure AMD.},
}
@article {pmid37934160,
year = {2023},
author = {Anders, P and Traber, GL and Hall, U and Garobbio, SA and Chan, EJ and Gabrani, C and Camenzind, H and Pfau, M and Herzog, M and Scholl, HPN},
title = {Evaluating Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration With the Quick Contrast Sensitivity Function.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {14},
pages = {7},
pmid = {37934160},
issn = {1552-5783},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Contrast Sensitivity ; Cross-Sectional Studies ; Prospective Studies ; *Macular Degeneration ; Eye ; },
abstract = {PURPOSE: The purpose of this study was to describe, validate, and compare the contrast sensitivity functions (CSFs) acquired with the novel quick CSF (qCSF) method from patients with early and intermediate age-related macular degeneration (eAMD and iAMD) and healthy controls.<br><br>METHODS: This is a cross-sectional analysis of contrast sensitivity (CS) and visual acuity (VA) baseline data from the prospective Multimodal Functional and Structural Visual System Characterization (MUMOVI) study. The qCSF testing was conducted with the manifold contrast vision meter (Adaptive Sensory Technology, San Diego, CA, USA). CS levels at spatial frequencies from 1 cycle per degree (CPD) to 18 CPD, the area underneath the logarithmic contrast sensitivity function (AULCSF), and contrast acuity (CA) were analyzed. The association of functional metrics with variables of interest was tested with linear models.<br><br>RESULTS: Ninety-four study eyes from 94 study patients were included in the analysis (13 patients with eAMD, 33 patients with iAMD, and 48 healthy controls). Significant differences between the eAMD and the iAMD model estimates were only found for CS at 1 CPD (t value = -2.9, P value = 0.006) and CS at 1.5 CPD (-2.7, 0.01). A specific association between smoking years and CS at 1 CPD (P = 0.02) and CS at 1.5 CPD (P = 0.03) could be described in patients with AMD.<br><br>CONCLUSIONS: The qCSF testing allows the fast measurement of the whole CSF, enabling the integration into clinical routine. We showed that novel qCSF-derived metrics detect slight functional differences between AMD stages, which testing by Pelli-Robson charts or VA testing would miss. This study, therefore, yields novel qCSF-derived candidate metrics for therapeutic trials in AMD.},
}
@article {pmid37933837,
year = {2024},
author = {Kaymak, H and Neller, K and Graff, B and Langenbucher, A and Seitz, B and Schwahn, H and Klabe, K},
title = {Contrast Adaptation in Pseudophakic Patients with Macular Disorders.},
journal = {Current eye research},
volume = {49},
number = {2},
pages = {207-213},
doi = {10.1080/02713683.2023.2273196},
pmid = {37933837},
issn = {1460-2202},
mesh = {Humans ; Visual Acuity ; *Presbyopia ; Pilot Projects ; *Retinal Diseases ; *Epiretinal Membrane ; *Macular Degeneration/diagnosis ; *Lenses, Intraocular ; },
abstract = {PURPOSE: To learn whether contrast adaptation, induced by positive spherical defocus, is compromised by macular disorders such as age-related macular degeneration (AMD) or epiretinal membranes (ERM) and to gain further insight in the functionality of the pathological macula and the level of "functional reserve" often postulated for the indication of presbyopia correcting IOLs.<br><br>METHODS: In a pilot study, patients with macular disorders, AMD and ERM, (n&#x2009;=&#x2009;10) and healthy volunteers (n&#x2009;=&#x2009;10) were tested to quantify contrast adaption after +4&#x2009;D defocus for 10&#x2009;min, by performing an interocular contrast matching task. Subjects manually adjusted the perceived contrast of the test patch as seen by the test eye to match to the contrast of a target patch with a fixed Michelson contrast of 0.2 as seen by the contralateral untreated eye.<br><br>RESULTS: Patients with macular disorders subjectively matched the 0.2 target contrast with a contrast of 0.24&#x2009;&#xb1;&#x2009;0.06 (mean&#x2009;&#xb1;&#x2009;SD) before adaptation and with a contrast of 0.19&#x2009;&#xb1;&#x2009;0.04 after adaptation (p&#x2009;<&#x2009;0.05). Accordingly, patients with macular disorders showed an induced contrast gain by adaptation of 0.05 (27%), which was not different from the control group, which showed an induced contrast gain by adaptation of 0.06 (35%).<br><br>CONCLUSION: Patients with mild and moderate macular disorders, such as AMD and ERM, show an induced contrast adaptation, i.e. a gain in contrast sensitivity, at 3.2 cpd, which is not different in level from the induced contrast adaptation in healthy subjects. Macular disorders do not prevent adaptation of the patient's visual system to low contrast or blurred retinal images. Therefore, the implantation of presbyopia correcting IOLs is not a strict exclusion criterion for these patients, but the progressive nature of the macular disorder must be taken into account.},
}
@article {pmid37933610,
year = {2023},
author = {Pfau, M and Künzel, SH and Pfau, K and Schmitz-Valckenberg, S and Fleckenstein, M and Holz, FG},
title = {Multimodal imaging and deep learning in geographic atrophy secondary to age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {101},
number = {8},
pages = {881-890},
pmid = {37933610},
issn = {1755-3768},
support = {EY014800/EY/NEI NIH HHS/United States ; R01EY034965/EY/NEI NIH HHS/United States ; R01 EY033365/EY/NEI NIH HHS/United States ; R01 EY034965/EY/NEI NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; R01EY033365/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy/diagnosis ; Artificial Intelligence ; *Deep Learning ; Fluorescein Angiography/adverse effects ; *Macular Degeneration/diagnosis ; Multimodal Imaging ; Tomography, Optical Coherence ; },
abstract = {Geographic atrophy (GA) secondary to age-related macular degeneration is among the most common causes of irreversible vision loss in industrialized countries. Recently, two therapies have been approved by the US FDA. However, given the nature of their treatment effect, which primarily involves a relative decrease in disease progression, discerning the individual treatment response at the individual level may not be readily apparent. Thus, clinical decision-making may have to rely on the quantification of the slope of GA progression before and during treatment. A panel of imaging modalities and artificial intelligence (AI)-based algorithms are available for such quantifications. This article aims to provide a comprehensive overview of the fundamentals of GA imaging, the procedures for diagnosis and classification using these images, and the cutting-edge role of AI algorithms in automatically deriving diagnostic and prognostic insights from imaging data.},
}
@article {pmid37933609,
year = {2023},
author = {Krogh Nielsen, M and Hinnerskov, JMV and Sørensen, TL},
title = {Geographic atrophy - Signs, symptoms, and quality of life.},
journal = {Acta ophthalmologica},
volume = {101},
number = {8},
pages = {896-902},
doi = {10.1111/aos.15794},
pmid = {37933609},
issn = {1755-3768},
mesh = {Humans ; Aged ; *Quality of Life/psychology ; *Geographic Atrophy ; Sickness Impact Profile ; Visual Acuity ; Vision, Ocular ; Surveys and Questionnaires ; },
abstract = {Geographic atrophy (GA) is a prevalent cause of vision loss among elderly and is associated with a significant loss of function. We reviewed the current literature to assess the effect of GA on patients' daily lives and well-being. We record and organize the signs, symptoms, and impacts that are important in life with GA. Further, we examined the impact of GA on vision-related quality of life. The main complaint among patients was difficulties regarding daily tasks, especially reading and other near activities. However, a large proportion of patients also reported fear, frustration, and anxiety as salient symptoms with large impact. Many patients do not have adequate information about their condition as well as the prognosis. The most commonly used measure of patient-reported outcome measure (PROM) is the National Eye Institute Visual Function Questionnaire (VFQ), that reflects the severity of impact on 12 subscales, from where near activities, general vision, mental health, and role difficulties had the lowest scores. Longitudinal studies of GA and the impact of low-vision rehabilitation efforts on health-related quality of life are sparse but suggest a significant improvement on several items. PROM is included in clinical trials, and so far, no drug has shown to improve the functional outcome in terms of PROM.},
}
@article {pmid37933608,
year = {2023},
author = {Vujosevic, S and Alovisi, C and Chakravarthy, U},
title = {Epidemiology of geographic atrophy and its precursor features of intermediate age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {101},
number = {8},
pages = {839-856},
doi = {10.1111/aos.15767},
pmid = {37933608},
issn = {1755-3768},
mesh = {Humans ; *Geographic Atrophy ; *Retinal Drusen/epidemiology ; Quality of Life ; *Macular Degeneration/epidemiology ; Retina ; },
abstract = {Globally age-related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers. The incidence and prevalence of GA varies across different geographic regions, with the highest rates in those of European ancestry. Although heterogeneity in definitions of GA and reporting strategy can explain some of the discrepancies, the data overall are consistent in showing a lower prevalence in other ethnicities such as those of Asian heritage. This is at present unexplained but thought to be due to the existence of protective factors such as differences in eye pigmentation, diet, environmental exposures and genetic variability. This review covers key aspects of the prevalence and incidence of the ocular precursor features of GA (large drusen, pigmentary abnormalities and reticular pseudo-drusen), the late stage of GA and factors that have been known to be associated with modifying risk including systemic, demographic, environment, genetic and ocular. Understanding the global epidemiology scenario is crucial for the prevention of and management of patients with GA.},
}
@article {pmid37933297,
year = {2023},
author = {Yu, L and Zhu, G and Zhang, Z and Xu, Z and Peng, W and Zeng, L and Yu, Y and Wang, S and Lin, Z and Zhang, X and Zhou, N and Zhang, L and Liang, L},
title = {Nano-Photosensitizer Directed Targeted Phototherapy Effective Against Oral Cancer in Animal Model.},
journal = {International journal of nanomedicine},
volume = {18},
number = {},
pages = {6185-6198},
pmid = {37933297},
issn = {1178-2013},
mesh = {Mice ; Animals ; Photosensitizing Agents/pharmacology ; Verteporfin/therapeutic use ; *Photochemotherapy ; Phototherapy ; *Mouth Neoplasms/drug therapy ; *Nanoparticles/chemistry ; Disease Models, Animal ; Cell Line, Tumor ; },
abstract = {BACKGROUND: Photodynamic therapy (PDT) has emerged as a promising strategy for oral cancer treatment. Verteporfin is a powerful photosensitizer and widely used in the treatment of macular degeneration. However, rare work has reported its potential in the treatment of oral cancer.<br><br>METHODS: In this study, we introduce an innovative approach of nano-photosensitizer based on Verteporfin, which was prepared by utilizing macrophage membrane to coat Verteporfin-loaded zeolitic imidazolate framework 8 (ZIF-8) for effective photodynamic therapy against oral cancer. Nanoparticle characteristics were assessed including size, zeta potential, and PDI. Cellular uptake studies were conducted using CAL-27 cells. Furthermore, inhibitory effects in both in vitro and in vivo settings were observed, ensuring biosafety. Assessment of anticancer efficacy involved tumor volume measurement, histological analyses, and immunohistochemical staining.<br><br>RESULTS: In vitro experiments indicated that the nano-photosensitizer showed efficient cellular uptake in the oral cancer cells. Upon the laser irradiation, the nano-photosensitizer induced the generation of reactive oxygen species (ROS), leading to cancer cell apoptosis. The in vivo experiments indicated that the coating with cell membranes enhanced the circulation time of nano-photosensitizer. Moreover, the specificity of the nano-photosensitizer to the cancer cells was also improved by the cell membrane-camouflaged structure in the tumor-bearing mouse model, which inhibited the tumor growth significantly by the photodynamic effect in the presence of laser irradiation.<br><br>CONCLUSION: Overall, our findings demonstrate the potential of macrophage membrane-coated ZIF-8-based nanoparticles loaded with Verteporfin for effective photodynamic therapy in oral cancer treatment. This nano-system holds promise for synergistic cancer therapy by combining the cytotoxic effects of PDT with the activation of the immune system, providing a novel therapeutic strategy for combating cancer.},
}
@article {pmid37933205,
year = {2024},
author = {Miller, A and Macnaughton, J and Crossland, MD and Latham, K},
title = {"I'm like something out of star wars": a qualitative investigation of the views of people with age-related macular degeneration regarding wearable electronic vision enhancement systems.},
journal = {Disability and rehabilitation},
volume = {46},
number = {19},
pages = {4476-4485},
doi = {10.1080/09638288.2023.2278179},
pmid = {37933205},
issn = {1464-5165},
mesh = {Humans ; *Macular Degeneration ; Female ; Male ; Aged ; *Wearable Electronic Devices ; *Qualitative Research ; Aged, 80 and over ; Adaptation, Psychological ; Interviews as Topic ; Middle Aged ; },
abstract = {PURPOSE: This study explores the initial views of people with age-related macular degeneration towards wearable electronic vision enhancement systems.<br><br>METHODS: Ten adults with age-related macular degeneration participated in semi-structured interviews, which were analysed using reflexive thematic analysis.<br><br>RESULTS: Four themes were identified. Firstly, participants spoke of the wide-ranging impact of sight loss and how current helpful coping strategies still had significant limitations, affecting their desire to seek new solutions. The second theme showed that "other people" offered welcomed support with existing electronic coping solutions and are needed to provide suitable advice and training. However, "other people" limited the acceptability of using new solutions in public places. The third theme captured participants' desire for a wearable aid providing image magnification and enhancement over a range of distances. The final theme covered the reality of some current wearable technology, perceived as heavy, enclosing, or strange in appearance. Appearance caused some to lose interest in use, although others reframed the devices' desired usefulness to solo and sedentary activities.<br><br>CONCLUSION: This population are interested in the potential benefits of wearable electronic vision enhancement systems. More work is needed to understand the suitability of current solutions due to participant concerns about training, appearance and performance.},
}
@article {pmid37929782,
year = {2023},
author = {Yu, C and Bakshi, A and Watts, GF and Renton, AE and Fulton-Howard, B and Goate, AM and Natarajan, P and Chasman, DI and Robman, L and Woods, RL and Guymer, R and Wolfe, R and Thao, LTP and McNeil, JJ and Tonkin, AM and Nicholls, SJ and Lacaze, P},
title = {Genome-Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene.},
journal = {Journal of the American Heart Association},
volume = {12},
number = {21},
pages = {e031459},
pmid = {37929782},
issn = {2047-9980},
support = {U19 AG062682/AG/NIA NIH HHS/United States ; U01 AG029824/AG/NIA NIH HHS/United States ; R01 HL127564/HL/NHLBI NIH HHS/United States ; R01 HL142711/HL/NHLBI NIH HHS/United States ; R01 EY026890/EY/NEI NIH HHS/United States ; U01 AG058635/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Humans ; *Cardiovascular Diseases/genetics ; Cholesterol Ester Transfer Proteins/genetics ; Cholesterol, HDL ; Cholesterol, LDL ; *Genome-Wide Association Study ; Lipoproteins, HDL/metabolism ; Quantitative Trait Loci ; Risk Factors ; },
abstract = {Background The risk of atherosclerotic cardiovascular disease (ASCVD) increases sharply with age. Some older individuals, however, remain unaffected despite high predicted risk. These individuals may carry cardioprotective genetic variants that contribute to resilience. Our aim was to assess whether asymptomatic older individuals without prevalent ASCVD carry cardioprotective genetic variants that contribute to ASCVD resilience. Methods and Results We performed a genome-wide association study using a 10-year predicted ASCVD risk score as a quantitative trait, calculated only in asymptomatic older individuals aged ≥70 years without prevalent ASCVD. Our discovery genome-wide association study of N=12 031 ASCVD event-free individuals from the ASPREE (Aspirin in Reducing Events in the Elderly) trial identified 2 independent variants, rs9939224 (P<5×10[-8]) and rs56156922 (P<10[-6]), in the CETP (cholesteryl ester transfer protein) gene. The CETP gene is a regulator of plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) levels, and it is a therapeutic drug target. The associations were replicated in the UK Biobank (subpopulation of N=13 888 individuals aged ≥69 years without prevalent ASCVD). Carriers of the identified CETP variants (versus noncarriers) had higher plasma high-density lipoprotein cholesterol levels, lower plasma low-density lipoprotein cholesterol levels, and reduced risk of incident ASCVD events during follow-up. Expression quantitative trait loci analysis predicted the identified CETP variants reduce CETP gene expression across various tissues. Previously reported associations between genetic CETP inhibition and increased risk of age-related macular degeneration were not observed among the 3917 ASPREE trial participants with retinal imaging and genetic data available. Conclusions Common genetic variants in the CETP gene region are associated with cardiovascular resilience during aging. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.},
}
@article {pmid37927331,
year = {2022},
author = {Tholen, P and Brown, CN and Keil, C and Bayir, A and Zeng, HH and Haase, H and Thompson, RB and Lengyel, I and Yücesan, G},
title = {A 2,7-dichlorofluorescein derivative to monitor microcalcifications.},
journal = {Molecular systems design &amp; engineering},
volume = {7},
number = {11},
pages = {1415-1421},
pmid = {37927331},
issn = {2058-9689},
support = {R01 EY030443/EY/NEI NIH HHS/United States ; },
abstract = {Herein, we report the crystal structure of 2,7-dichlorofluorescein methyl ester (DCF-ME) and its fluorescence response to hydroxyapatite binding. The reported fluorophore is very selective for staining the bone matrix and provides turn-on fluorescence upon hydroxyapatite binding. The reported fluorophore can readily pass the cell membrane of the C2C12 cell line, and it is non-toxic for the cell line. The reported fluorophore DCF-ME may find applications in monitoring bone remodeling and microcalcification as an early diagnosis tool for breast cancer and age-related macular degeneration.},
}
@article {pmid37927315,
year = {2023},
author = {Kesav, N and Mehra, AA and Schmaier, AH and Sobol, W},
title = {Severe Subconjunctival Hemorrhage After Intravitreal Injection in a Patient With Hemophilia A.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {4},
pages = {333-336},
pmid = {37927315},
issn = {2474-1272},
abstract = {Purpose: To report a patient with severe hemophilia A who received intravitreal antivascular endothelial growth factor (anti-VEGF) for exudative age-related macular degeneration (AMD). Methods: A case and its findings were analyzed. A systematic literature was performed. Results: A patient with severe hemophilia A received intravitreal anti-VEGF for exudative AMD, after which he developed a severe subconjunctival hemorrhage requiring hemostatic intervention. The effects of anti-VEGF in patients with preexisting blood-clotting disorders, such as classic hemophilia, have not been widely reported in the current literature. Conclusions: This case illustrates that precautions must be taken when performing ocular procedures on patients with serious hemostasis disorders.},
}
@article {pmid37926095,
year = {2023},
author = {Zheng, Q and Shen, T and Xu, M and Tan, L and Shen, Z and Hong, C},
title = {Association between Dietary Consumption of Vitamin B1 and Advanced Age-Related Macular Degeneration: A Cross-Sectional Observational Study in NHANES 2005-2008.},
journal = {Ophthalmic research},
volume = {66},
number = {1},
pages = {1353-1361},
doi = {10.1159/000534819},
pmid = {37926095},
issn = {1423-0259},
mesh = {Humans ; Adult ; Nutrition Surveys ; Cross-Sectional Studies ; *Thiamine ; *Macular Degeneration/epidemiology ; Risk Factors ; },
abstract = {INTRODUCTION: One of the most common conditions that causes permanent blindness globally is age-related macular degeneration (AMD). The purpose of the present study was to determine the association between vitamin B1 consumption and the prevalence of late AMD in a representative US sample.<br><br>METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008 were utilized for this cross-sectional analysis. The logistic regression model was used to evaluate the association between vitamin B1 consumption levels and late AMD.<br><br>RESULTS: Our study included 5,107 people aged 40 years old and above. Vitamin B1 intake levels were inversely associated with the prevalence of late AMD, with OR being 0.40 (95% CI: 0.26-0.62), 0.53 (95% CI: 0.29-0.94), 0.55 (95% CI: 0.31-0.99) for the crude model 1, adjusted model 2, and fully adjusted model 3, respectively.<br><br>CONCLUSION: Our study found that vitamin B1 intake levels were inversely associated with the prevalence of late AMD in the USA. Further randomized clinical trials among multiple centers are still warranted to investigate the longitudinal and causal relationship between vitamin B1 intake and late AMD.},
}
@article {pmid37922601,
year = {2023},
author = {Xu, K and Huang, S and Yang, Z and Zhang, Y and Fang, Y and Zheng, G and Lin, B and Zhou, M and Sun, J},
title = {Automatic detection and differential diagnosis of age-related macular degeneration from color fundus photographs using deep learning with hierarchical vision transformer.},
journal = {Computers in biology and medicine},
volume = {167},
number = {},
pages = {107616},
doi = {10.1016/j.compbiomed.2023.107616},
pmid = {37922601},
issn = {1879-0534},
mesh = {Humans ; Aged ; *Deep Learning ; Diagnosis, Differential ; *Macular Degeneration/diagnostic imaging ; Diagnostic Techniques, Ophthalmological ; Photography/methods ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, highlighting the need for early and accurate detection. In this study, we proposed DeepDrAMD, a hierarchical vision transformer-based deep learning model that integrates data augmentation techniques and SwinTransformer, to detect AMD and distinguish between different subtypes using color fundus photographs (CFPs). The DeepDrAMD was trained on the in-house WMUEH training set and achieved high performance in AMD detection with an AUC of 98.76% in the WMUEH testing set and 96.47% in the independent external Ichallenge-AMD cohort. Furthermore, the DeepDrAMD effectively classified dryAMD and wetAMD, achieving AUCs of 93.46% and 91.55%, respectively, in the WMUEH cohort and another independent external ODIR cohort. Notably, DeepDrAMD excelled at distinguishing between wetAMD subtypes, achieving an AUC of 99.36% in the WMUEH cohort. Comparative analysis revealed that the DeepDrAMD outperformed conventional deep-learning models and expert-level diagnosis. The cost-benefit analysis demonstrated that the DeepDrAMD offers substantial cost savings and efficiency improvements compared to manual reading approaches. Overall, the DeepDrAMD represents a significant advancement in AMD detection and differential diagnosis using CFPs, and has the potential to assist healthcare professionals in informed decision-making, early intervention, and treatment optimization.},
}
@article {pmid37925165,
year = {2024},
author = {Abdulaal, M and Donkor, R and Robertson, J and Lewis, S and Miller, DG and Schartman, J and Platt, S and Coney, JM},
title = {Early surgical displacement of submacular hemorrhage without tissue plasminogen activator use: one-year outcomes.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {59},
number = {5},
pages = {e582-e589},
doi = {10.1016/j.jcjo.2023.10.005},
pmid = {37925165},
issn = {1715-3360},
mesh = {Humans ; Retrospective Studies ; *Visual Acuity/physiology ; Male ; *Retinal Hemorrhage/diagnosis/physiopathology/surgery/etiology ; Female ; *Vitrectomy/methods ; Aged ; *Tissue Plasminogen Activator/administration &amp; dosage ; *Tomography, Optical Coherence/methods ; Follow-Up Studies ; *Endotamponade/methods ; Treatment Outcome ; Middle Aged ; Time Factors ; Aged, 80 and over ; Fibrinolytic Agents/therapeutic use/administration &amp; dosage ; },
abstract = {OBJECTIVE: This study evaluated changes in best-corrected visual acuity and submacular hemorrhage (SMH) resolution in eyes after a single rapid subretinal displacement surgery using subretinal balanced saline solution and sterile air without tissue plasminogen activator (tPA).<br><br>DESIGN: A retrospective comparative interventional analysis.<br><br>PARTICIPANTS: Twenty-six eyes with thick SMH who underwent pars plana vitrectomy and subretinal fluid displacement without tPA from 2015 and 2021 and at least 1-year of follow-up.<br><br>METHODS: Surgical intervention included a standard small-gauge pars plana vitrectomy with subretinal displacement using balanced saline solution with subretinal sterile air and partial gas-air fluid exchange. Main outcome measures included degree of subfoveal SMH displacement, best and final postoperative visual acuities, and adverse events. Snellen acuity was converted to logMARs for statistical analysis.<br><br>RESULTS: The most common etiology associated with thick SMH (92.3%) was neovascular age-related macular degeneration. Within 1 month postoperatively, 21 patients (80.8%) saw complete subfoveal blood displacement. Most of the SMH surgical displacements were done within 1 week of presenting symptoms. Average preoperative duration of SMH was 3.60 &#xb1; 2.78 days (range, 1-12 days). Mean logMAR best-corrected visual acuity improved from 1.63 &#xb1; 0.58 (Snellen 20/800 baseline) to 0.90 &#xb1; 0.42 letters (Snellen 20/160) at last follow-up (p&#x202f;=&#x202f;0.001). This study's visual acuity improvement is comparable with that of prior studies using tPA. Early postoperative complications included 1 retinal detachment, 1 vitreous hemorrhage, and 1 macular hole.<br><br>CONCLUSION: Rapid surgery with subretinal balanced saline solution-sterile air injection without tPA was found to be effective for displacement of thick SMH with retinal function, visual acuity, and corneal refractive therapy improvement.},
}
@article {pmid37924946,
year = {2024},
author = {Izquierdo-Serra, J and Martin-Pinardel, R and Moll-Udina, A and Bernal-Morales, C and Garay-Aramburu, G and Sanchez-Monroy, J and Arruabarrena, C and Fernandez-Hortelano, A and Figueroa, MS and Abraldes, M and Lavid de Los Mozos, FJ and Zapata, MA and Ruiz-Moreno, JM and Broc-Iturralde, L and Gonzalez-Guijarro, J and Escobar-Barranco, JJ and Gallego-Pinazo, R and Parrado-Carrillo, A and Dotti-Boada, M and Alforja, S and Figueras-Roca, M and Barthelmes, D and Gillies, MC and Casaroli-Marano, RP and Zarranz-Ventura, J and , },
title = {Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {4},
pages = {350-359},
doi = {10.1016/j.oret.2023.10.022},
pmid = {37924946},
issn = {2468-6530},
mesh = {Humans ; *Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Intravitreal Injections ; Neovascularization, Pathologic ; *Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide.<br><br>DESIGN: Multicenter national nAMD database observational study.<br><br>SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide.<br><br>METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n&#xa0;= 711), type 2 (T2, n&#xa0;= 505), type 3 (T3, n&#xa0;= 315), and aneurysmal type 1 (A-T1, n&#xa0;= 75), according to the new proposed consensus classification.<br><br>MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation.<br><br>RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (&#xb1; standard deviation) baseline VA was significantly lower for T2 (49.4 &#xb1; 23.5 letters) compared with T1 (57.8 &#xb1; 20.8) and T3 (58.2 &#xb1; 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions.<br><br>CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37923770,
year = {2023},
author = {Baharlouei, Z and Rabbani, H and Plonka, G},
title = {Wavelet scattering transform application in classification of retinal abnormalities using OCT images.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {19013},
pmid = {37923770},
issn = {2045-2322},
mesh = {Humans ; *Macular Edema/diagnostic imaging ; *Diabetic Retinopathy/diagnostic imaging ; Tomography, Optical Coherence/methods ; Retina/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; },
abstract = {To assist ophthalmologists in diagnosing retinal abnormalities, Computer Aided Diagnosis has played a significant role. In this paper, a particular Convolutional Neural Network based on Wavelet Scattering Transform (WST) is used to detect one to four retinal abnormalities from Optical Coherence Tomography (OCT) images. Predefined wavelet filters in this network decrease the computation complexity and processing time compared to deep learning methods. We use two layers of the WST network to obtain a direct and efficient model. WST generates a sparse representation of the images which is translation-invariant and stable concerning local deformations. Next, a Principal Component Analysis classifies the extracted features. We evaluate the model using four publicly available datasets to have a comprehensive comparison with the literature. The accuracies of classifying the OCT images of the OCTID dataset into two and five classes were [Formula: see text] and [Formula: see text], respectively. We achieved an accuracy of [Formula: see text] in detecting Diabetic Macular Edema from Normal ones using the TOPCON device-based dataset. Heidelberg and Duke datasets contain DME, Age-related Macular Degeneration, and Normal classes, in which we achieved accuracy of [Formula: see text] and [Formula: see text], respectively. A comparison of our results with the state-of-the-art models shows that our model outperforms these models for some assessments or achieves nearly the best results reported so far while having a much smaller computational complexity.},
}
@article {pmid37922158,
year = {2023},
author = {Hass, DT and Zhang, Q and Autterson, GA and Bryan, RA and Hurley, JB and Miller, JML},
title = {Medium Depth Influences O2 Availability and Metabolism in Human RPE Cultures.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {14},
pages = {4},
pmid = {37922158},
issn = {1552-5783},
support = {K08 EY033420/EY/NEI NIH HHS/United States ; R01 EY006641/EY/NEI NIH HHS/United States ; R01 EY017863/EY/NEI NIH HHS/United States ; S10 OD028612/OD/NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; *Retina/metabolism ; Hypoxia/metabolism ; Glucose/pharmacology ; Lipids ; Cells, Cultured ; },
abstract = {PURPOSE: Retinal pigment epithelium (RPE) oxidative metabolism is critical for normal retinal function and is often studied in cell culture systems. Here, we show that conventional culture media volumes dramatically impact O2 availability, limiting oxidative metabolism. We suggest optimal conditions to ensure cultured RPE is in a normoxic environment permissive to oxidative metabolism.<br><br>METHODS: We altered the availability of O2 to human primary and induced pluripotent stem cell-derived RPE cultures directly via a hypoxia chamber or indirectly via the amount of medium over cells. We measured oxygen consumption rates (OCRs), glucose consumption, lactate production, 13C6-glucose and 13C5-glutamine flux, hypoxia inducible factor 1&#x3b1; (HIF-1&#x3b1;) stability, intracellular lipid droplets after a lipid challenge, transepithelial electrical resistance, cell morphology, and pigmentation.<br><br>RESULTS: Medium volumes commonly employed during RPE culture limit diffusion of O2 to cells, triggering hypoxia, activating HIF-1&#x3b1;, limiting OCR, and dramatically altering cell metabolism, with only minor effects on typical markers of RPE health. Media volume effects on O2 availability decrease acetyl-CoA utilization, increase glycolysis and reductive carboxylation, and alter the size and number of intracellular lipid droplets under lipid-rich conditions.<br><br>CONCLUSIONS: Despite having little impact on visible and typical markers of RPE culture health, media volume dramatically affects RPE physiology "under the hood." As RPE-centric diseases like age-related macular degeneration involve oxidative metabolism, RPE cultures need to be optimized to study such diseases. We provide guidelines for optimal RPE culture volumes that balance ample nutrient availability from larger media volumes with adequate O2 availability seen with smaller media volumes.},
}
@article {pmid37922157,
year = {2023},
author = {Borrelli, E and Reibaldi, M and Barresi, C and Berni, A and Introini, U and Bandello, F},
title = {Choroidal Hyper-Reflective Foci in Geographic Atrophy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {14},
pages = {5},
pmid = {37922157},
issn = {1552-5783},
mesh = {Humans ; *Geographic Atrophy/diagnosis/pathology ; Retrospective Studies ; Choroid/pathology ; *Macular Degeneration/complications/diagnosis/pathology ; Bruch Membrane/pathology ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; },
abstract = {PURPOSE: The purpose of this study was to describe the presence of choroidal hyper-reflective foci (HRF) on optical coherence tomography (OCT) in patients with geographic atrophy (GA). The relationship between the presence and quantity of choroidal HRF and other clinical and imaging factors was also investigated.<br><br>METHODS: A total of 40 participants (40 eyes) with GA and age-related macular degeneration (AMD) were retrospectively analyzed. OCT images were reviewed for the presence, characteristics, and localization of choroidal HRF. The amount of choroidal HRF was quantified in different choroidal layers by two different (i.e. threshold reflectivity and manual counting) methodologies. The primary outcome was to describe and quantify choroidal HRF and correlate them with GA lesion size.<br><br>RESULTS: Structural OCT images showed that all patients had multiple hyper-reflective deposits in different layers of the choroid. These hyper-reflective deposits in the choroid were located near Bruch's membrane or the edges of the blood vessels, particularly in the Sattler's layer, and none were observed inside the vessels. Choroidal HRF exhibited variable size and shape and varying effects on the posterior signal, including shadowing or hypertransmission. Mean &#xb1; SD number of choroidal HRF per B-scan was 21.5 &#xb1; 15.4 using the threshold reflectivity methodology and 25.1 &#xb1; 16.0 using the manual counting methodology. A significant correlation between the untransformed GA size and number of HRF was found, considering both quantitative strategies.<br><br>CONCLUSIONS: Hyper-reflective dots in the choroid of subjects with GA may be readily identified with structural OCT. These HRF might represent a natural component of the choroid that becomes more visible due to the absence of the retinal pigment epithelium.},
}
@article {pmid37921948,
year = {2023},
author = {Huther, A and Roh, S and Ramsey, DJ},
title = {Telehealth improves follow-up and monitoring of age-related macular degeneration during the COVID-19 pandemic.},
journal = {International ophthalmology},
volume = {43},
number = {12},
pages = {5031-5043},
pmid = {37921948},
issn = {1573-2630},
mesh = {Humans ; Pandemics ; Follow-Up Studies ; *COVID-19/epidemiology ; *Wet Macular Degeneration/diagnosis/epidemiology ; *Telemedicine ; Disease Progression ; },
abstract = {PURPOSE: To prevent vision loss, it is important to monitor patients with age-related macular degeneration (AMD) for the development of choroidal neovascularization. The coronavirus disease 2019 (COVID-19) pandemic caused many patients to miss or delay visits. To offset those gaps in care, providers utilized telehealth (TH) to evaluate patients for symptoms of disease progression and provide health education on the importance of continuous monitoring.<br><br>METHODS: This study evaluates the impact of TH encounters on the rate of return for recommended in-person examinations for 1103 patients with non-neovascular (dry) AMD seen in an outpatient ophthalmology clinic in 2019 and due for return evaluation after the outbreak of COVID-19 in 2020. Logistic regression analysis was used to identify demographic, clinical, and sociomedical factors associated with TH utilization and in-person return.<br><br>RESULTS: 422 patients (38%) utilized TH during the study period. Patients who completed a TH encounter were more likely to return for an in-person examination as compared with those who did not receive TH (OR: 1.8, CI 95%: 1.4-2.3, P&#x2009;<&#x2009;0.001). Completing a TH visit was associated with the detection of new wet AMD (OR: 3.3, 95% CI 1.04-10.6, P&#x2009;=&#x2009;0.043), as well as with an earlier return for those patients who were found to have disease progression (62&#x2009;&#xb1;&#x2009;54&#xa0;days vs. 100&#x2009;&#xb1;&#x2009;57&#xa0;days, P&#x2009;=&#x2009;0.049).<br><br>CONCLUSION: Completing a TH visit increased the rate at which patients with dry AMD returned for recommended in-person eye examinations. In many cases, this permitted the earlier detection of wet AMD, which is linked with achieving better outcomes.},
}
@article {pmid37921677,
year = {2024},
author = {Hakim, FE and Nagra, AK and Dhaliwal, DK},
title = {Descemet Stripping Only: Long-Term Outcomes.},
journal = {Cornea},
volume = {43},
number = {8},
pages = {994-998},
pmid = {37921677},
issn = {1536-4798},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; P30-EY08098//Research to Prevent Blindness/ ; },
mesh = {Humans ; *Visual Acuity/physiology ; Retrospective Studies ; Male ; Female ; *Fuchs' Endothelial Dystrophy/surgery/physiopathology ; Aged ; *Descemet Membrane/surgery ; Middle Aged ; Follow-Up Studies ; Aged, 80 and over ; Treatment Outcome ; Descemet Stripping Endothelial Keratoplasty/methods ; Endothelium, Corneal/pathology ; },
abstract = {PURPOSE: Descemet stripping only (DSO) is a relatively novel treatment for Fuchs endothelial corneal dystrophy (FECD). In this procedure, a central area of Descemet membrane and endothelium is removed without the insertion of donor tissue. Evaluation of long-term outcomes (≥5 years) after DSO is imperative to establish the validity of this procedure and to determine its role in the management of Fuchs endothelial dystrophy. Published outcomes are limited but promising. This study evaluates the 5- and 6-year outcomes of patients who had DSO at a single institution.<br><br>METHODS: This is a retrospective chart review of patients with FECD who underwent DSO in 2016 and 2017.<br><br>RESULTS: Eleven patients and 13 eyes met the criteria. Twelve of 13 eyes achieved corneal clearance. Two eyes had corneal decompensation requiring subsequent endothelial keratoplasty (EK). Of the 10 eyes that maintained clear corneas, 9 had a best-corrected visual acuity (BCVA) of at least 20/30 (mean logarithm of the minimim angle of resolution [logMAR] visual acuity [VA] 0.18 &#xb1; 0.16) at 5 years post-operatively (POY5). At 6 years, 7 of 8 eyes had a VA better than 20/40 (mean logMAR VA 0.17 &#xb1; 0.04). One patient had decreased VA due to progression of macular degeneration. Patients who required EK achieved good vision and corneal clearance.<br><br>CONCLUSIONS: This is the largest series of patients with long-term follow-up after DSO. Ten of the 13 eyes (77%) responded and maintained clear central corneas for at least 5 years. Patients with failed DSO can achieve corneal clearance and good vision with subsequent EK. These patient outcomes support the role of DSO in the management of patients with FECD.},
}
@article {pmid37921119,
year = {2024},
author = {Ho, S and Doig, GS and Ly, A},
title = {Diagnostic accuracy of community optometrists for age-related macular degeneration using colour fundus photographs: A pilot evaluation.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {44},
number = {1},
pages = {17-22},
doi = {10.1111/opo.13242},
pmid = {37921119},
issn = {1475-1313},
support = {//Guide Dogs NSW/ACT/ ; },
mesh = {Humans ; Female ; Adult ; Male ; *Optometrists ; Pilot Projects ; *Geographic Atrophy/diagnosis ; Angiogenesis Inhibitors ; Color ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration ; },
abstract = {PURPOSE: The accurate diagnosis of age-related macular degeneration (AMD) represents an important step in delaying and preventing vision loss and achieving optimal patient care. Therefore, this pilot study aimed to estimate the diagnostic accuracy of community optometrists for identifying AMD using colour fundus photographs (CFPs) to support sample size calculations for subsequent definitive studies.<br><br>METHODS: Five practising community optometrists were invited to classify a total of 1023 CFPs for the (1) presence of AMD, and, if applicable, (2) stage of AMD (early/intermediate/late geographic atrophy/late neovascular AMD). Diagnosis by referral centre clinicians formed the reference standard. Diagnostic accuracy was assessed by the area under the receiver operating characteristic curve (aROC). Sensitivity, specificity, positive and negative predictive values were also calculated.<br><br>RESULTS: Of the 1023 CFPs included in the study, 226 images were of AMD and 797 images were of other ocular conditions or no abnormal findings. Participating community optometrists had a mean (SD) age of 30.2 (8.9) years, 60.0% (3/5) were female and the mean number of years practising in primary eye care was 5.4 (5.4) years. Community optometrists demonstrated excellent performance for diagnosing AMD, with an aROC of 0.86 (95% CI 0.83 to 0.89), sensitivity of 84.5% (95% CI 79.1 to 89.0) and specificity of 88.0% (95% CI 85.5 to 90.1). The aROC (95% CI) for diagnosing early, intermediate, late geographic atrophy and late neovascular AMD was 0.82 (0.73 to 0.91), 0.76 (0.72 to 0.81), 0.69 (0.49 to 0.90) and 0.55 (0.34 to 0.75), respectively.<br><br>CONCLUSIONS: These results justify the need for an appropriately powered definitive study to assess community clinicians' diagnostic accuracy for AMD.},
}
@article {pmid37921040,
year = {2023},
author = {Zhou, C and Li, S and Ye, L and Chen, C and Liu, S and Yang, H and Zhuang, P and Liu, Z and Jiang, H and Han, J and Jiang, Y and Zhou, L and Zhou, X and Xiao, J and Zhang, C and Wen, L and Lan, C and Wang, Y and Sun, T and Jiang, L and Xie, P and Chen, F and Liang, G and Fu, D and Zhang, T and Shi, X and Song, Z and Liu, X and Li, S and Li, P and Xu, X and Wei, Q and Wang, W and Huang, X and De, Z and Deng, A and Ding, L and Pan, X and Wen, H and Zhang, Z and Lv, H and Zhang, J and Tian, X and Deng, Z and Wang, H and Wang, F and Wang, Y and Zhao, H and Fang, Y and Wu, Y and Wu, Y and Shen, N and Li, B and Li, X and Dai, H and Zhao, N and Sun, X and Zheng, Z and Liu, K and Xu, X},
title = {Visual impairment and blindness caused by retinal diseases: A nationwide register-based study.},
journal = {Journal of global health},
volume = {13},
number = {},
pages = {04126},
pmid = {37921040},
issn = {2047-2986},
mesh = {Adult ; Humans ; Female ; Aged ; *Persons with Visual Disabilities ; Visual Acuity ; Blindness/epidemiology/etiology ; *Vision, Low/etiology/complications ; Vision Disorders/etiology/complications ; *Retinal Diseases/epidemiology/complications ; *Macular Degeneration/complications/epidemiology ; *Diabetic Retinopathy ; Prevalence ; },
abstract = {BACKGROUND: Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care planning and allocation of medical resources. The purpose of this study is to describe the proportion of visual impairment and blindness caused by major retinal diseases in China.<br><br>METHODS: A nationwide register-based study of vitreoretinal disease covering all 31 provinces (51 treating centres) of mainland China. A total of 28&#x2009;320 adults diagnosed with retinal diseases were included. Participants underwent standardised ocular examinations, which included best-corrected visual acuity (BCVA), dilated-fundus assessments, and optical coherence tomography. Visual impairment and blindness are defined using BCVA according to the World Health Organization (WHO) (visual impairment: <20/63-&#x2265;20/400; blindness: <20/400) and the United States (visual impairment: <20/40-&#x2265;20/200; blindness: <20/200) definitions. The risk factors of vision loss were explored by logistic regression analyses.<br><br>RESULTS: Based on the WHO definitions, the proportions for unilateral visual impairment and blindness were 46% and 18%, respectively, whereas those for bilateral visual impairment and blindness were 31% and 3.3%, respectively. Diabetic retinopathy (DR) accounts for the largest proportion of patients with visual impairment (unilateral visual impairment: 32%, bilateral visual impairment: 60%) and blindness (unilateral blindness: 35%; bilateral blindness: 64%). Other retinal diseases that contributed significantly to vision loss included age-related macular degeneration, myopic maculopathy, retinal vein occlusion, and rhegmatogenous retinal detachment and other macular diseases. Women (bilateral vision loss: P&#x2009;=&#x2009;0.011), aged patients (unilateral vision loss: 45-64 years: P&#x2009;<&#x2009;0.001, &#x2265;65 years: P&#x2009;<&#x2009;0.001; bilateral vision loss: 45-64 years: P&#x2009;=&#x2009;0.003, &#x2265;65 years: P&#x2009;<&#x2009;0.001 (reference: 18-44 years)) and those from Midwest China (unilateral and bilateral vision loss: both P&#x2009;<&#x2009;0.001) were more likely to suffer from vision loss.<br><br>CONCLUSIONS: Retinal disorders cause substantial visual burden among patients with retinal diseases in China. DR, the predominant retinal disease, is accountable for the most prevalent visual disabilities. Better control of diabetes and scaled-up screenings are warranted to prevent DR. Specific attention should be paid to women, aged patients, and less developed regions.},
}
@article {pmid37920982,
year = {2024},
author = {Savastano, A and Ferrara, S and Sasso, P and Savastano, MC and Crincoli, E and Caporossi, T and De Vico, U and Vidal Aroca, F and Francione, G and Sammarco, L and Gambini, G and Fedeli, C and Di Nardo, E and Rizzo, S},
title = {Smaller-Incision new-generation implantable miniature telescope: Three-months follow-up study.},
journal = {European journal of ophthalmology},
volume = {34},
number = {4},
pages = {1111-1118},
doi = {10.1177/11206721231212545},
pmid = {37920982},
issn = {1724-6016},
mesh = {Humans ; Female ; Prospective Studies ; Male ; Follow-Up Studies ; *Visual Acuity/physiology ; Aged ; *Quality of Life ; Telescopes ; Intraocular Pressure/physiology ; Aged, 80 and over ; Middle Aged ; Prostheses and Implants ; Time Factors ; },
abstract = {PURPOSE: To evaluate three months follow-up of SING IMT implant in patients affected by late-stage AMD.<br><br>DESIGN: Prospective cohort study.<br><br>SUBJECTS: In a total of 80 eyes of 40 patients who underwent the enrollment tests, 11 patients' eyes affected by late-stage AMD matched the inclusion criteria and underwent SING IMT implant from February to June 2022.<br><br>METHODS: Before surgery, each patient underwent the enrollment examination to verify inclusion and exclusion criteria.<br><br>MAIN OUTCOME MEASURES: BCVA for distance and for near, IOP, ACD and ECD were evaluated at 1 and 3 months follow up. Also quality of life in doing the activities of daily life was evaluated.<br><br>RESULTS: BCVA for distance and for near improved from baseline to 3 months follow up (23.91&#x2009;&#xb1;&#x2009;9.418 ETDRS letters and 59.09&#x2009;&#xb1;&#x2009;11.58 ETDRS letters respectively (p&#x2009;<&#x2009;0.001). An endothelial cell loss was shown (p&#x2009;<&#x2009;0.001), with a rate of cell density reduction around 8.3% (baseline vs 3 months).<br><br>CONCLUSIONS: SING IMT could be a valid surgical device to improve patients' sight and quality of life which have been deteriorated by late-stage macular degeneration. Further studies with more patients and longer follow up are needed to confirm our results.},
}
@article {pmid37920746,
year = {2023},
author = {Takemoto, M and Kitamura, Y and Kakisu, M and Shimizu, D and Baba, T},
title = {Retinal Pigment Epithelial Tears after Ex-PRESS Filtration Surgery in a Glaucoma Patient with a History of Ischemic Optic Neuropathy.},
journal = {Case reports in ophthalmological medicine},
volume = {2023},
number = {},
pages = {6645156},
pmid = {37920746},
issn = {2090-6722},
abstract = {BACKGROUND: To describe a case of retinal pigment epithelial tears (RPE tears) and serous retinal detachment (SRD) after Ex-PRESS filtration surgery for primary open-angle glaucoma (POAG) combined with ischemic optic neuropathy. Case Presentation. This case report involved a 69-year-old woman who underwent Ex-PRESS filtration surgery for right POAG. She had a history of systemic arteriosclerotic disease and subacute progressive visual field loss due to suspected ischemic optic neuropathy in her right eye. The right preoperative visual acuity was 0.7, and intraocular pressure (IOP) was 19 mmHg with maximum glaucoma eye drops. RPE detachment was not observed in the fundus. On day 9 after surgery, the IOP was 6 mmHg, and mild choroidal detachment was observed. On day 13, although IOP remained almost unchanged at 7 mmHg, bullous SRD was observed in the inferior retina, including the macula, and RPE tears were observed along the superior arcade vessel. While subretinal fluid gradually decreased with increasing IOP, tractional retinal folds persisted along the superior arcade, accompanied by macular degeneration.<br><br>CONCLUSION: We experienced a case of RPE tears after Ex-PRESS filtration surgery. In addition to choroidal detachment in the setting of hypotony, a pathologic condition causing structural fragility of the RPE layer may contribute to the development of RPE tears.},
}
@article {pmid37916108,
year = {2023},
author = {Liu, W and Hu, Q and Zhang, F and Shi, K and Wu, J},
title = {Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study.},
journal = {Heliyon},
volume = {9},
number = {10},
pages = {e21073},
pmid = {37916108},
issn = {2405-8440},
abstract = {OBJECTIVE: Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology.<br><br>METHODS: Genome-wide association studies were employed to identify single nucleotide polymorphisms (SNPs) showing significant correlations with osteocalcin. Subsequently, A two-sample Mendelian randomization analysis was conducted utilizing the inverse-variance-weighted (IVW) technique to assess the causal relationship between osteocalcin and various types of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and vascular dementia (VD). This approach aimed to minimize potential sources of confounding bias and provide more robust results. Multivariable MR (MVMR) analysis was conducted to adjust for potential genetic pleiotropy.<br><br>RESULTS: The study employed three SNPs, namely rs71631868, rs9271374, and rs116843408, as genetic tools to evaluate the causal association of osteocalcin with dementia. The IVW analysis indicated that osteocalcin may have a potential protective effect against AD with an odds ratio (OR) of 0.790 (95&#xa0;% CI: 0.688-0.906; P&#xa0;<&#xa0;0.001). However, no significant relationship was observed between osteocalcin and other types of dementia. Furthermore, the MVMR analysis indicated that the impact of osteocalcin on AD remained consistent even after adjusting for age-related macular degeneration and Type 2 diabetes with an OR of 0.856 (95&#xa0;% CI: 0.744-0.985; P&#xa0;=&#xa0;0.030).<br><br>CONCLUSIONS: Our findings provide important insights into the role of osteocalcin in the pathogenesis of AD. Future research is required to clarify the underlying mechanisms and their clinical applications.},
}
@article {pmid37913992,
year = {2024},
author = {Pandit, SA and Momenaei, B and Wakabayashi, T and Mansour, HA and Vemula, S and Durrani, AF and Pashaee, B and Kazan, AS and Ho, AC and Klufas, M and Regillo, C and Yonekawa, Y and Hsu, J and Kuriyan, A and Chiang, A},
title = {Clinical Outcomes of Faricimab in Patients with Previously Treated Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {4},
pages = {360-366},
doi = {10.1016/j.oret.2023.10.018},
pmid = {37913992},
issn = {2468-6530},
mesh = {Humans ; Aged ; Aged, 80 and over ; Ranibizumab ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Treatment Outcome ; Tomography, Optical Coherence/methods ; *Retinal Detachment/drug therapy ; *Macular Degeneration/drug therapy ; *Antibodies, Bispecific ; },
abstract = {PURPOSE: To assess the anatomic and functional outcomes in eyes with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF therapy in response to intravitreal faricimab.<br><br>DESIGN: Retrospective, interventional, consecutive case series.<br><br>SUBJECTS: Patients with previously treated nAMD who received &#x2265; 4 consecutive injections of faricimab were included. The study period was from March through November&#xa0;2022.<br><br>METHODS: Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT), maximum fibrovascular pigment epithelial detachment (fvPED) height, and Snellen visual acuity (VA) were obtained. Generalized estimating equations were used to analyze the change in CFT, maximum fvPED height, and logarithm of the minimum angle of resolution VA.<br><br>MAIN OUTCOME MEASURES: Change in CFT, maximum fvPED height, and Snellen VA before faricimab and after &#x2265; 4 faricimab intravitreal injections.<br><br>RESULTS: During the study period, 218 eyes of 191 patients met inclusion criteria. Mean age was 79.9 (range, 70.6-89.2) years. The mean number of intravitreal anti-VEGF injections received before faricimab was 34.2 (range, 6.4-62). The following results were found after &#x2265; 4 faricimab injections. Mean logarithm of the minimum angle of resolution VA before switching to faricimab was 0.58 (Snellen VA &#x223c;20/76; range, 20/22-20/264) and was 0.55 (Snellen VA &#x223c;20/71; range, 20/21-20/235; P&#xa0;= 0.20) after switching. Mean maximum fvPED height was 195.0 (range, 50.2-339.8) &#x3bc;m before switching to faricimab and improved to 165.0 (range, 33.6-296.4; P < 0.001) &#x3bc;m after switching. Mean CFT was 354.8 (range, 184.7-524.9) &#x3bc;m before switching to faricimab and improved to 306.6 (range, 144.4-468.8; P < 0.001) after switching. The proportion of eyes with intraretinal fluid was 36.7% (80/218 eyes) before switching, and decreased to 24.8% (54/218 eyes, P < 0.001) after switching. The proportion of eyes with subretinal fluid was 53.2% (116/218 eyes) before switching and decreased to 26.6% (58/218 eyes, P < 0.001) after switching.<br><br>CONCLUSIONS: Intravitreal faricimab may improve anatomic outcomes in patients with previously treated nAMD, while maintaining VA in the short-term.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37905874,
year = {2024},
author = {Abyadeh, M and Gupta, V and Paulo, JA and Mahmoudabad, AG and Shadfar, S and Mirshahvaladi, S and Gupta, V and Nguyen, CTO and Finkelstein, DI and You, Y and Haynes, PA and Salekdeh, GH and Graham, SL and Mirzaei, M},
title = {Amyloid-beta and tau protein beyond Alzheimer's disease.},
journal = {Neural regeneration research},
volume = {19},
number = {6},
pages = {1262-1276},
pmid = {37905874},
issn = {1673-5374},
support = {R01 GM132129/GM/NIGMS NIH HHS/United States ; },
abstract = {The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, post-translational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.},
}
@article {pmid37903455,
year = {2024},
author = {Pandya, BU and Grinton, M and Mandelcorn, ED and Felfeli, T},
title = {RETINAL OPTICAL COHERENCE TOMOGRAPHY IMAGING BIOMARKERS: A Review of the Literature.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {3},
pages = {369-380},
pmid = {37903455},
issn = {1539-2864},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Epiretinal Membrane ; *Uveitis ; *Retinal Drusen ; Biomarkers ; Atrophy ; Retrospective Studies ; },
abstract = {PURPOSE: The aim of this literature review was to summarize novel optical coherence tomography (OCT) imaging biomarkers that have recently been described in the literature and are frequently encountered clinically.<br><br>METHODS: The literature was reviewed to identify novel OCT biomarkers reported to date. A descriptive summary of all terms and representative illustrations were provided to highlight the most relevant features.<br><br>RESULTS: Thirty-seven OCT terminologies were identified. The vitreomacular interface disorder group included the four stages of epiretinal membrane, macular pseudohole, tractional lamellar hole (LH), degenerative LH, cotton ball sign, and foveal crack sign. The age-related macular degeneration group included outer retinal tubulation, multilayered pigment epithelial detachment, prechoroidal cleft, onion sign, double-layer sign, complete outer retinal atrophy, complete retinal pigment epithelium and outer retinal atrophy, and reticular pseudodrusen. The uveitic disorder group consisted of bacillary layer detachment, syphilis placoid, rain-cloud sign, and pitchfork sign. The disorders relating to the toxicity group included flying saucer sign and mitogen-activated protein kinase (MEK) inhibitor-associated retinopathy. The disorders associated with the systemic condition group included choroidal nodules and needle sign. The pachychoroid spectrum group included pachychoroid and brush border pattern. The vascular disorder group included pearl necklace sign, diffuse retinal thickening, disorganization of retinal inner layers, inner nuclear layer microcysts, hyperreflective retinal spots, paracentral acute middle maculopathy, and acute macular neuroretinopathy. The miscellaneous group included omega sign (&#x3c9;), macular telangiectasia (type 2), and omega sign (&#x3a9;).<br><br>CONCLUSIONS: Thirty-seven OCT terminologies were summarized, and detailed illustrations consolidating the features of each biomarker were included. A nuanced understanding of OCT biomarkers and their clinical significance is essential because of their predictive and prognostic value.},
}
@article {pmid37903288,
year = {2024},
author = {Begaj, T and Jeong, D and Park, JG and Runner, MM and Capone, A and Dass, AB and Drenser, KA and Faia, LJ and Farley, ND and Garretson, BR and Hassan, TS and Mahmoud, TH and Margherio, A and Raphaelian, PV and Randhawa, S and Ruby, AJ and Sneed, S and Rao, P and Wolfe, JD and Williams, GA},
title = {LONG-TERM USE OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {2},
pages = {222-229},
doi = {10.1097/IAE.0000000000003961},
pmid = {37903288},
issn = {1539-2864},
mesh = {Humans ; Child, Preschool ; Aged, 80 and over ; Child ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Bevacizumab/therapeutic use ; Vascular Endothelial Growth Factor A ; Endothelial Growth Factors ; Retrospective Studies ; Intravitreal Injections ; Retinal Hemorrhage/drug therapy ; *Macular Degeneration/drug therapy ; *Endophthalmitis/drug therapy/epidemiology ; *Wet Macular Degeneration/diagnosis/drug therapy ; Treatment Outcome ; },
abstract = {PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment.<br><br>METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for &#x2265;5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated.<br><br>RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline (P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage.<br><br>CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (&#x2265;20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (&#x2264;20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.},
}
@article {pmid37903056,
year = {2023},
author = {Elbaz-Hayoun, S and Rinsky, B and Hagbi-Levi, S and Grunin, M and Chowers, I},
title = {CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {37903056},
issn = {2050-084X},
mesh = {Humans ; Animals ; *Retinal Degeneration/pathology ; Ependymoglial Cells/metabolism ; Photoreceptor Cells/metabolism ; Retina/metabolism ; *Macular Degeneration/metabolism ; Cell Death ; Disease Models, Animal ; Receptors, CCR1/genetics/metabolism ; },
abstract = {Mononuclear cells are involved in the pathogenesis of retinal diseases, including age-related macular degeneration (AMD). Here, we examined the mechanisms that underlie macrophage-driven retinal cell death. Monocytes were extracted from patients with AMD and differentiated into macrophages (hMdɸs), which were characterized based on proteomics, gene expression, and ex vivo and in vivo properties. Using bioinformatics, we identified the signaling pathway involved in macrophage-driven retinal cell death, and we assessed the therapeutic potential of targeting this pathway. We found that M2a hMdɸs were associated with retinal cell death in retinal explants and following adoptive transfer in a photic injury model. Moreover, M2a hMdɸs express several CCRI (C-C chemokine receptor type 1) ligands. Importantly, CCR1 was upregulated in Müller cells in models of retinal injury and aging, and CCR1 expression was correlated with retinal damage. Lastly, inhibiting CCR1 reduced photic-induced retinal damage, photoreceptor cell apoptosis, and retinal inflammation. These data suggest that hMdɸs, CCR1, and Müller cells work together to drive retinal and macular degeneration, suggesting that CCR1 may serve as a target for treating these sight-threatening conditions.},
}
@article {pmid37902056,
year = {2023},
author = {Ferro Desideri, L and Artemiev, D and Bernardi, E and Paschon, K and Zandi, S and Zinkernagel, M and Anguita, R},
title = {Investigational drugs inhibiting complement for the treatment of geographic atrophy.},
journal = {Expert opinion on investigational drugs},
volume = {32},
number = {11},
pages = {1009-1016},
doi = {10.1080/13543784.2023.2276759},
pmid = {37902056},
issn = {1744-7658},
mesh = {Humans ; Complement Inactivating Agents/adverse effects ; Drugs, Investigational/adverse effects ; *Geographic Atrophy/drug therapy ; Immunologic Factors/adverse effects ; *Macular Degeneration/drug therapy ; },
abstract = {INTRODUCTION: Geographic atrophy (GA) is a progressive form of age-related macular degeneration (AMD) that leads to severe visual impairment and central vision loss. Traditional treatment options for GA are limited, highlighting the need for new therapeutic approaches. In recent years, targeting the complement system has emerged as a promising strategy for the treatment of GA.<br><br>AREAS COVERED: This expert opinion article reviews the investigational drugs inhibiting the complement cascade for the treatment of GA. Specifically, it focuses on the recent FDA approved pegcetacoplan, a C3 complement inhibitor, and avacincaptad pegol, a C5 complement inhibitor, highlighting their potential efficacy and safety profiles based on clinical trial data.<br><br>EXPERT OPINION: FDA approval of intravitreal pegcetacoplan and avacincaptad pegol marks significant progress in the landscape of GA treatment. However, variable results from trials underscore the complex nature of GA and the importance of patient selection. Complement inhibition holds promise, but ongoing research is vital to refine treatment strategies and offer improved outcomes for GA patients.},
}
@article {pmid37901649,
year = {2023},
author = {Forsaa, VA and Thomseth, VM},
title = {Reticular Pseudodrusen Voids after Rhegmatogenous Retinal Detachment.},
journal = {Case reports in ophthalmology},
volume = {14},
number = {1},
pages = {400-404},
pmid = {37901649},
issn = {1663-2699},
abstract = {We present a case of reticular pseudodrusen (RPD) regression on multimodal retinal imaging following a rhegmatogenous retinal detachment. Two mechanisms of action can be postulated. The subretinal deposits dissolve due to voluminous subretinal fluid during retinal separation from the retinal pigment epithelium and are in turn mechanically cleared during retinal re-attachment surgery. Alternatively, an RPD clearance is facilitated by enhanced phagocytic activity of macrophages and microglial cells as a response to acute retinal stress.},
}
@article {pmid37901412,
year = {2023},
author = {Gholami, S and Lim, JI and Leng, T and Ong, SSY and Thompson, AC and Alam, MN},
title = {Federated learning for diagnosis of age-related macular degeneration.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1259017},
pmid = {37901412},
issn = {2296-858X},
support = {R15 EY035804/EY/NEI NIH HHS/United States ; R21 EY035271/EY/NEI NIH HHS/United States ; },
abstract = {This paper presents a federated learning (FL) approach to train deep learning models for classifying age-related macular degeneration (AMD) using optical coherence tomography image data. We employ the use of residual network and vision transformer encoders for the normal vs. AMD binary classification, integrating four unique domain adaptation techniques to address domain shift issues caused by heterogeneous data distribution in different institutions. Experimental results indicate that FL strategies can achieve competitive performance similar to centralized models even though each local model has access to a portion of the training data. Notably, the Adaptive Personalization FL strategy stood out in our FL evaluations, consistently delivering high performance across all tests due to its additional local model. Furthermore, the study provides valuable insights into the efficacy of simpler architectures in image classification tasks, particularly in scenarios where data privacy and decentralization are critical using both encoders. It suggests future exploration into deeper models and other FL strategies for a more nuanced understanding of these models' performance. Data and code are available at https://github.com/QIAIUNCC/FL_UNCC_QIAI.},
}
@article {pmid37901244,
year = {2023},
author = {Cao, Y and Ibrahim, KS and Li, X and Wong, A and Wu, Y and Yu, XD and Zhou, X and Tan, Z and He, Z and Craft, JA and Shu, X},
title = {Chinese medicine, Qijudihuang pill, mediates cholesterol metabolism and regulates gut microbiota in high-fat diet-fed mice, implications for age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1274401},
pmid = {37901244},
issn = {1664-3224},
mesh = {Animals ; Mice ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Medicine, Chinese Traditional ; RNA, Ribosomal, 16S ; Inflammation ; Cholesterol ; *Macular Degeneration/drug therapy/etiology ; },
abstract = {BACKGROUND: Traditional Chinese Medicines have been used for thousands of years but without any sound empirical basis. One such preparation is the Qijudihuang pill (QP), a mixture of eight herbs, that has been used in China for the treatment of various conditions including age-related macular degeneration (AMD), the most common cause of blindness in the aged population. In order to explain the mechanism behind the effect of QP, we used an AMD model of high-fat diet (HFD) fed mice to investigate cholesterol homeostasis, oxidative stress, inflammation and gut microbiota.<br><br>METHODS: Mice were randomly divided into three groups, one group was fed with control diet (CD), the other two groups were fed with high-fat-diet (HFD). One HFD group was treated with QP, both CD and the other HFD groups were treated with vehicles. Tissue samples were collected after the treatment. Cholesterol levels in retina, retinal pigment epithelium (RPE), liver and serum were determined using a commercial kit. The expression of enzymes involved in cholesterol metabolism, inflammation and oxidative stress was measured with qRT-PCR. Gut microbiota was analyzed using 16S rRNA sequencing.<br><br>RESULTS: In the majority of the lipid determinations, analytes were elevated by HFD but this was reversed by QP. Cholesterol metabolism including the enzymes of bile acid (BA) formation was suppressed by HFD but again this was reversed by QP. BAs play a major role in signaling between host and microbiome and this is disrupted by HFD resulting in major changes in the composition of colonic bacterial communities. Associated with these changes are predictions of the metabolic pathway complexity and abundance of individual pathways. These concerned substrate breakdowns, energy production and the biosynthesis of pro-inflammatory factors but were changed back to control characteristics by QP.<br><br>CONCLUSION: We propose that the ability of QP to reverse these HFD-induced effects is related to mechanisms acting to lower cholesterol level, oxidative stress and inflammation, and to modulate gut microbiota.},
}
@article {pmid37900796,
year = {2023},
author = {Thomas, M and Benfield, J and Morales, J},
title = {Case Report of Seronegative Cancer-Associated Retinopathy in a Patient with Small Cell Lung Carcinoma.},
journal = {Case reports in oncology},
volume = {16},
number = {1},
pages = {791-796},
pmid = {37900796},
issn = {1662-6575},
abstract = {Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome characterized by autoimmune destruction of photoreceptor cells. It is associated with several tumor types, including small cell lung carcinoma (SCLC). Corticosteroids have been the mainstay treatment for CAR, although no therapeutic standard has truly been established. A 66-year-old female with significant smoking history and age-related macular degeneration (ARMD) presented with rapidly declining bilateral visual acuity. Ophthalmologic examination findings appeared consistent with the known diagnosis of ARMD but did not otherwise present a clear alternative etiology. Imaging with a computed tomography (CT) scan revealed a right hilar mass which was confirmed to be limited stage SCLC based on a subsequent biopsy and further imaging with a positron emission tomography/computed tomography (PET/CT) scan. Antibody testing was negative for anti-recoverin antibodies. The patient experienced a complete response to chemoradiation with cisplatin and etoposide; however, her ocular symptoms did not respond to a combined treatment approach with corticosteroids, plasmapheresis, and intravenous immunoglobulin (IVIG). While CAR represents a rare condition in SCLC, cases that are seronegative for anti-recoverin are even less common. Further, the diagnosis of CAR by ophthalmologic examination may be more challenging in patients with pre-existing ocular diseases, such as macular degeneration. Clinicians should have suspicion for paraneoplastic blindness in patients with known risk factors for malignancy, whose ocular symptoms are inconsistent with exam findings.},
}
@article {pmid37899750,
year = {2023},
author = {Lewallen, CF and Chien, A and Maminishkis, A and Hirday, R and Reichert, D and Sharma, R and Wan, Q and Bharti, K and Forest, CR},
title = {A biologically validated mathematical model for decoding epithelial apical, basolateral, and paracellular electrical properties.},
journal = {American journal of physiology. Cell physiology},
volume = {325},
number = {6},
pages = {C1470-C1484},
pmid = {37899750},
issn = {1522-1563},
support = {R01 NS102727/NS/NINDS NIH HHS/United States ; U01 MH106027/MH/NIMH NIH HHS/United States ; RF1 AG079269/AG/NIA NIH HHS/United States ; R01 DA029639/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; Epithelium/metabolism ; *Epithelial Cells ; *Retinal Pigment Epithelium/physiology ; Cell Membrane/metabolism ; Models, Theoretical ; },
abstract = {Epithelial tissues form selective barriers to ions, nutrients, waste products, and infectious agents throughout the body. Damage to these barriers is associated with conditions such as celiac disease, cystic fibrosis, diabetes, and age-related macular degeneration. Conventional electrophysiology measurements like transepithelial resistance can quantify epithelial tissue maturity and barrier integrity but are limited in differentiating between apical, basolateral, and paracellular transport pathways. To overcome this limitation, a combination of mathematical modeling, stem cell biology, and cell physiology led to the development of 3 P-EIS, a novel mathematical model and measurement technique. 3 P-EIS employs an intracellular pipette and extracellular electrochemical impedance spectroscopy to accurately measure membrane-specific properties of epithelia, without the constraints of prior models. 3 P-EIS was validated using electronic circuit models of epithelia with known resistances and capacitances, confirming a median error of 19% (interquartile range: 14%-26%) for paracellular and transcellular resistances and capacitances (n = 5). Patient stem cell-derived retinal pigment epithelium tissues were measured using 3 P-EIS, successfully isolating the cellular responses to adenosine triphosphate. 3 P-EIS enhances quality control in epithelial cell therapies and has extensive applicability in drug testing and disease modeling, marking a significant advance in epithelial physiology.NEW &amp; NOTEWORTHY This interdisciplinary paper integrates mathematics, biology, and physiology to measure epithelial tissue's apical, basolateral, and paracellular transport pathways. A key advancement is the inclusion of intracellular voltage recordings using a sharp pipette, enabling precise quantification of relative impedance changes between apical and basolateral membranes. This enhanced electrochemical impedance spectroscopy technique offers insights into epithelial transport dynamics, advancing disease understanding, drug interactions, and cell therapies. Its broad applicability contributes significantly to epithelial physiology research.},
}
@article {pmid37899575,
year = {2024},
author = {Viggiano, P and Buonamassa, R and Grassi, MO and Boscia, G and Borrelli, E and Landini, L and Evangelista, F and Malerba, MG and Alessio, G and Boscia, F},
title = {Immediate effect of anti-VEGF injections on optic nerve head: Correlation between intraocular pressure and anatomical peripapillary changes.},
journal = {European journal of ophthalmology},
volume = {34},
number = {4},
pages = {1174-1182},
doi = {10.1177/11206721231210749},
pmid = {37899575},
issn = {1724-6016},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Angiogenesis Inhibitors/administration &amp; dosage ; Fluorescein Angiography ; Follow-Up Studies ; *Intraocular Pressure/physiology/drug effects ; Intravitreal Injections ; *Nerve Fibers/pathology ; *Optic Disk/blood supply ; *Receptors, Vascular Endothelial Growth Factor/administration &amp; dosage ; Recombinant Fusion Proteins/administration &amp; dosage ; Retinal Ganglion Cells/pathology/drug effects ; Tomography, Optical Coherence ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Visual Acuity/physiology ; Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; },
abstract = {PURPOSE: This study was designed to investigate retinal nerve fiber layer (RNFL) and radial peripapillary capillaries (RPC) changes on optical coherence tomography (OCT) angiography and OCT thickness alterations associated with acutely increased intraocular pressure after intravitreal injections.<br><br>METHODS: This observational clinical study was conducted on 35 eyes (35 patients) with treatment-na&#xef;ve age-related macular degeneration (AMD) and type 1 or type 2 MNV were enrolled. All patients underwent anti-vascular endothelial grow factor (VEGF) intravitreal injections with 0.05-mL aflibercept (2 mg) between January 2022 and October 2022. Peripapillary OCT angiography perfusion density, retinal nerve fiber layer thickness, and intraocular pressure (IOP) were measured before and immediately after intravitreal injections. In particular, the analysis was performed at the following visits: (T0) 5 to 15&#x2005;min before the injection of aflibercept; (T1) 2 to 5&#x2005;min after the injection of aflibercept. Paired t-test was used to compare pre-injection and post-injection values.<br><br>RESULTS: The mean baseline IOP (T0) value was 17.26&#x2009;&#xb1;&#x2009;2.4&#x2005;mmHg and the immediate post-injection IOP (T1) mean value was 34.7&#x2009;&#xb1;&#x2009;11.50&#x2005;mmHg (P&#x2009;<&#x2009;0.01). The mean global RNFL thickness before and immediately after the injection was 100.9&#x2009;&#xb1;&#x2009;18.8&#x2005;m and 98.6&#x2009;&#xb1;&#x2009;17.4&#x2005;m (P&#x2009;=&#x2009;0.001). Furthermore, the topographical RNFL analysis showed significant thickness reduction of the nasal and inferior sectors after the procedure when compared to T0 (P&#x2009;=&#x2009;0.046 and P&#x2009;=&#x2009;0.001). On the contrary, the mean RCP density changes at T1 did not reach statistically significant (P&#x2009;=&#x2009;0.636). Furthermore, we found a significant negative correlation between the retinal nerve fiber layer global thickness and the IOP changes (Pearson's correlation&#x2009;=&#x2009;-0.126; P&#x2009;=&#x2009;0.031). In particular, the nasal RNFL region showed a significant negative correlations with IOP values (Pearson's correlation&#x2009;=&#x2009;-0.198, P&#x2009;=&#x2009;0,046).<br><br>CONCLUSIONS: We reported acute IOP changes that are associated with reduced RNFL thickness in a group of patients undergoing intravitreal injections of anti-VEGF drugs for neovascular age-related macular degeneration. Moreover, topographical sub-analysis revealed that the nasal RNFL region is most prone to IOP fluctuations. This finding may explain the sudden visual acuity change in patients immediately after injection and may sustain injuries to optic nerve head structures producing glaucomatous damage.},
}
@article {pmid37899281,
year = {2023},
author = {Park, S and Lee, J and Park, JB and Kim, ES and Yu, SY and Kang, MS and Kim, K},
title = {Diagnosing Polypoidal Choroidal Vasculopathy Using Color Fundus Photography, Optical Coherence Tomography, and Optical Coherence Tomography Angiography.},
journal = {Korean journal of ophthalmology : KJO},
volume = {37},
number = {6},
pages = {468-476},
pmid = {37899281},
issn = {2092-9382},
mesh = {Humans ; Male ; Middle Aged ; Aged ; Aged, 80 and over ; Female ; Tomography, Optical Coherence/methods ; Choroid/pathology ; Polypoidal Choroidal Vasculopathy ; Fluorescein Angiography/methods ; Cross-Sectional Studies ; Photography ; *Choroidal Neovascularization/diagnosis ; *Polyps/diagnosis ; Retrospective Studies ; Indocyanine Green ; Fundus Oculi ; },
abstract = {PURPOSE: To compare the diagnostic accuracy of differentiating polypoidal choroidal vasculopathy (PCV) from exudative age-related macular degeneration (AMD), using color fundus photography (CFP), optical coherence tomography (OCT), and swept-source OCT angiography (SS-OCTA) without using indocyanine green angiography (ICGA).<br><br>METHODS: Treatment-naive eyes with exudative AMD that underwent CFP, OCT, SS-OCTA, and ICGA imaging before treatment were identified. Images of each patient were categorized into two sets (set A, CFP + OCT; set B, CFP + SS-OCTA). In set B, both the en face and cross-sectional B scans were analyzed. Each set was reviewed by two graders, and it was determined whether the presumed diagnosis was PCV. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for the diagnosis of PCV were assessed for each set by comparing diagnoses that included ICGA. The number of polypoidal lesions in each set was calculated and compared to ICGA.<br><br>RESULTS: A total of 94 eyes from 94 patients with AMD were included in the study, of which 66.0% were male, and the mean age was 71.8 &#xb1; 9.0 years. The PCV diagnosis rate using ICGA was 45.7%. The sensitivity was 0.88 for set A and 0.93 for set B, while the specificity was 0.94 for set A and 0.96 for set B. The AUC was 0.90 (95% confidence interval [CI], 0.83-0.97) for set A and 0.96 (95% CI, 0.90-1.00) for set B. Set A detected 1.28 &#xb1; 0.91 polypoidal lesions, while set B detected 1.47 &#xb1; 1.01; ICGA showed 1.51 &#xb1; 0.86.<br><br>CONCLUSIONS: This study highlights that, without using ICGA, both CFP combined with OCT and CFP combined with SS-OCTA demonstrate high sensitivity, specificity, and AUC in diagnosing PCV. It is evident that SS-OCTA contributes to enhancing sensitivity, specificity, and AUC for PCV diagnosis.},
}
@article {pmid37898443,
year = {2023},
author = {Mehta, N and Dangas, K and Ditmarsch, M and Rensen, PCN and Dicklin, MR and Kastelein, JJP},
title = {The evolving role of cholesteryl ester transfer protein inhibition beyond cardiovascular disease.},
journal = {Pharmacological research},
volume = {197},
number = {},
pages = {106972},
doi = {10.1016/j.phrs.2023.106972},
pmid = {37898443},
issn = {1096-1186},
mesh = {Humans ; *Cardiovascular Diseases/drug therapy/etiology ; Cholesterol, HDL ; Cholesterol Ester Transfer Proteins ; *Diabetes Mellitus, Type 2/drug therapy/complications ; *Alzheimer Disease/complications ; Cholesterol/metabolism ; Apolipoproteins/metabolism ; *Sepsis/complications ; },
abstract = {The main role of cholesteryl ester transfer protein (CETP) is the transfer of cholesteryl esters and triglycerides between high-density lipoprotein (HDL) particles and triglyceride-rich lipoprotein and low-density lipoprotein (LDL) particles. There is a long history of investigations regarding the inhibition of CETP as a target for reducing major adverse cardiovascular events. Initially, the potential effect on cardiovascular events of CETP inhibitors was hypothesized to be mediated by their ability to increase HDL cholesterol, but, based on evidence from anacetrapib and the newest CETP inhibitor, obicetrapib, it is now understood to be primarily due to reducing LDL cholesterol and apolipoprotein B. Nevertheless, evidence is also mounting that other roles of HDL, including its promotion of cholesterol efflux, as well as its apolipoprotein composition and anti-inflammatory, anti-oxidative, and anti-diabetic properties, may play important roles in several diseases beyond cardiovascular disease, including, but not limited to, Alzheimer's disease, diabetes, and sepsis. Furthermore, although Mendelian randomization analyses suggested that higher HDL cholesterol is associated with increased risk of age-related macular degeneration (AMD), excess risk of AMD was absent in all CETP inhibitor randomized controlled trial data comprising over 70,000 patients. In fact, certain HDL subclasses may, in contrast, be beneficial for treating the retinal cholesterol accumulation that occurs with AMD. This review describes the latest biological evidence regarding the relationship between HDL and CETP inhibition for Alzheimer's disease, type 2 diabetes mellitus, sepsis, and AMD.},
}
@article {pmid37898281,
year = {2024},
author = {Tseng, VL and Kitayama, K and Yu, F and Coleman, AL},
title = {Prevalence and Severity of Glaucoma in the California Medicare Population.},
journal = {American journal of ophthalmology},
volume = {259},
number = {},
pages = {25-34},
doi = {10.1016/j.ajo.2023.10.018},
pmid = {37898281},
issn = {1879-1891},
mesh = {Humans ; Male ; Female ; Aged ; United States/epidemiology ; Aged, 80 and over ; Medicare ; *Glaucoma, Open-Angle/diagnosis/epidemiology ; Retrospective Studies ; Prevalence ; Cross-Sectional Studies ; *Glaucoma/diagnosis/epidemiology ; *Glaucoma, Angle-Closure/epidemiology ; California/epidemiology ; },
abstract = {PURPOSE: To examine the prevalence of glaucoma by type and severity in the 2019 California (CA) Medicare population, and to identify associated demographic and systemic factors.<br><br>DESIGN: Retrospective cross-sectional design.<br><br>METHODS: The study population included all 2019 CA Medicare beneficiaries &#x2265;65 years of age with Part A and Part B coverage. Outcomes included prevalence of any glaucoma, primary open angle glaucoma (POAG), secondary open angle glaucoma (SOAG), and angle closure glaucoma (ACG). Covariates included age, sex, race and ethnicity, Charlson Comorbidity Index (CCI) score, pseudophakia, and age-related macular degeneration. Logistic regression modeling was used to examine multivariable predictors of each type of glaucoma.<br><br>RESULTS: Of 5,856,491 beneficiaries in the 2019 California Medicare population, there were 220,662 (3.8%) with any glaucoma, 171,988 (2.9%) with POAG, 8,827 (0.2%) with SOAG, and 12,978 (0.2%) with ACG. The largest proportion of beneficiaries had moderate to severe glaucoma (68,553 of 220,662 [31.0%] for any glaucoma moderate stage, 3,168 of 12,978 [24.4%] for ACG severe stage). Multivariable predictors of any glaucoma included age &#x2265;85 years vs 65 to 69 years (adjusted odds ratio [aOR] = 2.03, 95% CI = 2.00, 2.06), female vs male sex (aOR = 1.03, 95% CI = 1.02, 1.04), Black vs non-Hispanic White race and ethnicity (aOR = 1.70, 95% CI = 1.67, 1.73), and CCI &#x2265;5 vs 0 (aOR = 5.59, 95% = 5.51, 5.67).<br><br>CONCLUSIONS: In the 2019 CA Medicare population, multiple demographic and systemic factors were associated with increased likelihood of glaucoma, and beneficiaries with glaucoma had a high prevalence of moderate to severe disease. Strategies are needed to improve early screening and diagnosis for elderly individuals at risk for glaucoma in California.},
}
@article {pmid37897411,
year = {2023},
author = {Kitao, M and Yamaguchi, A and Tomioka, T and Kai, K and Kamei, Y and Sugimoto, K and Akagawa, M},
title = {Astaxanthin protects human ARPE-19 retinal pigment epithelium cells from blue light-induced phototoxicity by scavenging singlet oxygen.},
journal = {Free radical research},
volume = {57},
number = {6-12},
pages = {430-443},
doi = {10.1080/10715762.2023.2277144},
pmid = {37897411},
issn = {1029-2470},
mesh = {Humans ; Aged ; *Singlet Oxygen/metabolism/pharmacology ; Reactive Oxygen Species/metabolism ; Blue Light ; Retinal Pigment Epithelium/metabolism ; Oxidative Stress ; Apoptosis ; Xanthophylls/pharmacology ; *Macular Degeneration/drug therapy/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is one of an increasing number of diseases that causes irreversible impairment and loss of vision in the elderly. AMD occurs by oxidative stress-mediated apoptosis of retinal pigment epithelium cells. The onset of AMD may be positively correlated with the exposure to blue light. We screened food-derived carotenoids for cytoprotective action against blue light irradiation using human ARPE-19 retinal pigment epithelium cells. This study revealed that blue light irradiation triggered apoptosis and oxidative stress in all-trans-retinal (atRAL)-exposed ARPE-19 cells by generating singlet oxygen ([1]O2), leading to significant cell death. We found that astaxanthin, a potent anti-oxidative xanthophyll abundant in several marine organisms including microalgae, salmon, and shrimp, significantly suppresses blue light-induced apoptotic cell death of atRAL-exposed ARPE-19 cells by scavenging [1]O2. Mechanistic studies using the blue-light irradiated cells also demonstrated that the cytoprotective effects of astaxanthin can be attributed to scavenging of [1]O2 directly. Our results suggest the potential value of astaxanthin as a dietary strategy to prevent blue light-induced retinal degeneration including AMD.},
}
@article {pmid37897394,
year = {2023},
author = {Taha, AA and Lazar, D and Julin, C and Sørensen, TL},
title = {Use of optical coherence tomography angiography for the diagnosis of age-related macular degeneration.},
journal = {Danish medical journal},
volume = {70},
number = {10},
pages = {},
pmid = {37897394},
issn = {2245-1919},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Prospective Studies ; Angiogenesis Inhibitors ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration ; Angiography ; Fluorescein Angiography/methods ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) causes approximately 9% of all blindness worldwide. The introduction of optical coherence tomography angiography (OCT-A) has revealed a potential for non-invasive diagnosis of neovascular AMD (nAMD), but has yet to be proven an accurate method for nAMD diagnosis. The purpose of this study was to map the clinical use of OCT-A in nAMD diagnosis and to investigate the agreement between two consultants in diagnosing nAMD.<br><br>METHODS: A survey was administered to assess Danish ophthalmologists in nAMD diagnostic modalities. Furthermore, a prospective observational cohort study was conducted in which two consultants graded Triton and Heidelberg OCT-A in patients with suspected nAMD.<br><br>RESULTS: A total of 21 ophthalmologists completed the survey. OCT-A combined with structural OCT was the first choice for the majority (81%), whereas dye-based ophthalmic angiography was used when in doubt of the diagnosis. OCT-A was used to guide treatment decisions in 64% of patients. Some ophthalmologists (48%) had no formal OCT-A training. In the second part of the study, an agreement was recorded between the two consultants in 86% of the cases with Triton OCT-A and 66% with Heidelberg OCT-A.<br><br>CONCLUSIONS: OCT-A with structural OCT has become a primary diagnostic method of nAMD, but national guidelines are lacking. Future implementation of new diagnostic technology of nAMD should include trial-based guidelines and physician training.<br><br>FUNDING: None.<br><br>TRIAL REGISTRATION: Not relevant.},
}
@article {pmid37896188,
year = {2023},
author = {Wu, T and Liu, C and Kannan, RM},
title = {Systemic Dendrimer-Peptide Therapies for Wet Age-Related Macular Degeneration.},
journal = {Pharmaceutics},
volume = {15},
number = {10},
pages = {},
pmid = {37896188},
issn = {1999-4923},
support = {EY001865//Wilmer Core Grant/ ; Arnall Patz Distinguished Professorship//Johns Hopkins Endowed Professorships/ ; },
abstract = {Wet age-related macular degeneration (AMD) is an end-stage event in a complex pathogenesis of macular degeneration, involving the abnormal growth of blood vessels at the retinal pigment epithelium driven by vascular endothelial growth factor (VEGF). Current therapies seek to interrupt VEGF signaling to halt the progress of neovascularization, but a significant patient population is not responsive. New treatment modalities such as integrin-binding peptides (risuteganib/Luminate/ALG-1001) are being explored to address this clinical need but these treatments necessitate the use of intravitreal injections (IVT), which carries risks of complications and restricts its availability in less-developed countries. Successful systemic delivery of peptide-based therapeutics must overcome obstacles such as degradation by proteinases in circulation and off-target binding. In this work, we present a novel dendrimer-integrin-binding peptide (D-ALG) synthesized with a noncleavable, "clickable" linker. In vitro, D-ALG protected the peptide payload from enzymatic degradation for up to 1.5 h (~90% of the compound remained intact) in a high concentration of proteinase (2 mg/mL) whereas ~90% of free ALG-1001 was degraded in the same period. Further, dendrimer conjugation preserved the antiangiogenic activity of ALG-1001 in vitro with significant reductions in endothelial vessel network formation compared to untreated controls. In vivo, direct intravitreal injections of ALG-1001 and D-ALG produced reductions in the CNV lesion area but in systemically dosed animals, only D-ALG produced significant reductions of CNV lesion area at 14 days. Imaging data suggested that the difference in efficacy may be due to more D-ALG remaining in the target area than ALG-1001 after administration. The results presented here offer a clinically relevant route for peptide therapeutics by addressing the major obstacles that these therapies face in delivery.},
}
@article {pmid37893574,
year = {2023},
author = {Ueji, N and Mase, Y and Kubo, A and Matsubara, H and Chujo, S and Matsui, Y and Kondo, M},
title = {Intraocular Inflammation Secondary to Intravitreal Brolucizumab Injection for Neovascular Age-Related Macular Degeneration in a Patient with Cognitive Impairment.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {10},
pages = {},
pmid = {37893574},
issn = {1648-9144},
mesh = {Male ; Humans ; Aged ; Angiogenesis Inhibitors/adverse effects ; *Vision, Low ; Inflammation ; *Retinal Detachment/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; *Macular Degeneration/complications/drug therapy ; },
abstract = {Background and Objectives: Brolucizumab (IVBr) is a recently introduced anti-vascular endothelial growth factor (anti-VEGF) which has been found to be very effective in treating neovascular age-related macular degeneration (nAMD). We reported our findings in a case of nAMD that developed intraocular inflammation (IOI) after IVBr injections. Materials and Methods: A 79-year-old man was referred to our hospital complaining of reduced vision in both eyes of one-month's duration. His decimal best-corrected visual acuity (BCVA) was 0.9 in the right eye and 1.0 in the left eye. He was diagnosed with nAMD in the left eye and was treated with intravitreal aflibercept (IVA). Despite the three-monthly IVA injections, the serous retinal pigment epithelial detachment (PED) and subretinal fluid (SRF) remained, and the VA gradually decreased to 0.1. Because of the patient being refractory to aflibercept treatment, we switched to 3-monthly IVBr injections. The BCVA gradually improved to 0.3 and optical coherence tomography (OCT) showed an absence of the serous PED and SRF. Three weeks after his third IVBr, he returned to our hospital with a complaint of reduced vision in his left eye that he first noted two weeks earlier. Our examination of the left eye showed signs of IOI mainly in the anterior chamber. The inflammation improved with topical steroids but the treatment of the IOI was delayed for two weeks. The patient was instructed that it was important to begin the treatment as soon as the symptoms of IOI developed. We then performed the Mini-Mental State Examination (MMSE), and his score indicated that he had cognitive impairment. Conclusions: We concluded that before beginning IVBr treatment in nAMD patients, a careful assessment must be made of the cognitive status of the patient.},
}
@article {pmid37893547,
year = {2023},
author = {Ristic, D and Resan, M and Pancevski, I and Ristic, P and Vukosavljevic, M and Cvetkovic, M and Pajic, B},
title = {Correlation of the OCT Double-Layer Sign with Type 1 Non-Exudative Neovascularization on OCT-A in Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {10},
pages = {},
pmid = {37893547},
issn = {1648-9144},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Prospective Studies ; *Macular Degeneration/diagnostic imaging ; Neovascularization, Pathologic ; Biomarkers ; Retrospective Studies ; },
abstract = {Background and Objectives: Early diagnosis of the exudative form of age-related macular degeneration (AMD) is very important for a timely first treatment, which is directly related to the preservation of functional visual acuity over a long period. The goal of this paper was to examine the correlation between the double-layer sign (DLS) and the presence of non-exudative macular neovascularization (MNV). Materials and Methods: Our research included 60 patients with AMD, exudative in one eye and non-exudative in the other eye. We analyzed only the non-exudative form using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). The patients were classified into three groups, depending on the duration of the disease (<2 years, 2 to 5 years, >5 years). The onset of the disease was deemed the moment of establishing a diagnosis of exudative AMD in one eye. We defined the presence or absence of a DLS using OCT and the presence of non-exudative MNV using OCT-A, both on 3 × 3 mm and 6 × 6 mm sections. DLS was used as a projection biomarker for non-exudative MNV, with the aim of establishing a rapid diagnosis and achieving early treatment of the disease. Results: We found that there was a statistically significant correlation between the DLS diagnosed using OCT and non-exudative MNV diagnosed by OCT-A for both 3 × 3 mm (p < 0.001) and 6 × 6 mm (p < 0.001) imaging. There was a statistically significant difference between the frequencies of both DLS and MNV in Groups I and III on both 3 × 3 and 6 × 6 mm imaging. A statistically significant difference was also noted in the frequencies of DLS and MNV on 6 × 6 mm imaging, but not on 3 × 3 mm imaging, between Groups I and II. No differences were found between the frequencies of DLS and MNV between Groups II and III. Conclusions: The DLS on OCT can be used as a projection biomarker to assess the presence of a non-exudative MNV.},
}
@article {pmid37891392,
year = {2023},
author = {Biswas, A and Choudhury, AD and Bisen, AC and Agrawal, S and Sanap, SN and Verma, SK and Mishra, A and Kumar, S and Bhatta, RS},
title = {Trends in Formulation Approaches for Sustained Drug Delivery to the Posterior Segment of the Eye.},
journal = {AAPS PharmSciTech},
volume = {24},
number = {8},
pages = {217},
pmid = {37891392},
issn = {1530-9932},
mesh = {Humans ; Delayed-Action Preparations/therapeutic use ; Eye ; Drug Delivery Systems ; Liposomes/therapeutic use ; *Macular Degeneration/drug therapy ; *Eye Diseases/drug therapy ; },
abstract = {The eye, an intricate organ comprising physical and physiological barriers, poses a significant challenge for ophthalmic physicians seeking to treat serious ocular diseases affecting the posterior segment, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Despite extensive efforts, the delivery of therapeutic drugs to the rear part of the eye remains an unresolved issue. This comprehensive review delves into conventional and innovative formulation strategies for drug delivery to the posterior segment of the eye. By utilizing alternative nanoformulation approaches such as liposomes, nanoparticles, and microneedle patches, researchers and clinicians can overcome the limitations of conventional eye drops and achieve more effective drug delivery to the posterior segment of the eye. These innovative strategies offer improved drug penetration, prolonged residence time, and controlled release, enhancing therapeutic outcomes for ocular diseases. Moreover, this article explores recently approved delivery systems that leverage diverse polymer technologies, such as chitosan and hyaluronic acid, to regulate drug-controlled release over an extended period. By offering a comprehensive understanding of the available formulation strategies, this review aims to empower researchers and clinicians in their pursuit of developing highly effective treatments for posterior-segment ocular diseases.},
}
@article {pmid37890814,
year = {2024},
author = {Zhuang, X and Su, Y and Li, M and Zhang, L and Mi, L and Ji, Y and Deng, F and Xiao, O and Zhang, X and Zhou, L and Cao, D and He, G and Zeng, Y and Pu, J and Hao, X and Chen, X and Gan, Y and Zhang, Y and Wen, F},
title = {A prospective observation of influence of anti-VEGF on optic disc vasculature in nAMD patients.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {45},
number = {},
pages = {103863},
doi = {10.1016/j.pdpdt.2023.103863},
pmid = {37890814},
issn = {1873-1597},
mesh = {Humans ; Infant ; *Optic Disk/blood supply ; Prospective Studies ; *Photochemotherapy/methods ; Photosensitizing Agents ; Retinal Vessels ; Vascular Endothelial Growth Factors ; },
abstract = {BACKGROUND: This study aims to investigate the short-term changes in relatively normal retinal vessels following anti-vascular endothelial growth factor (anti-VEGF) therapy in nAMD patients, an area that currently represents a research gap.<br><br>METHODS: In this prospective study, we enrolled patients newly diagnosed with neovascular age-related macular degeneration (nAMD) and received standardized monthly anti-VEGF therapy for three months. Follow-ups were conducted at baseline and 1-week, 1-month, 2-months and 3-months post first injection. Assessment indicators included radial peripapillary capillary vascular density (RPC-VD) and retinal nerve fiber layer (RNFL) thickness in different optic disk regions using optical coherence tomography angiography, as well as intraocular pressure (IOP).<br><br>RESULTS: 68 nAMD patients (68 eyes) were included in this study. Significant reductions of RPC-VD and increases of RNFL thickness primarily in the nasal regions were observed 1-week post anti-VEGF (adjusted P < 0.05). Significant negative correlations were found between 1-week changes in RPC-VD and RNFL thickness in the nasal sectors (P < 0.05). From 1 to 3 months post-injection, RPC-VD and RNFL thickness essentially returned to baseline levels. Throughout the follow-up periods, IOP remained stable (P > 0.05).<br><br>CONCLUSION: Anti-VEGF treatments transiently influence the relatively normal retinal vessels, which might lead to nerve fiber edema, predominantly on the nasal side of the optic disk.},
}
@article {pmid37890690,
year = {2024},
author = {Wang, YX and Wang, Q and Jonas, RA and Jonas, JB},
title = {Prevalence and Associations of Peripheral Arterial Disease in China: The Beijing Eye Study.},
journal = {American journal of ophthalmology},
volume = {258},
number = {},
pages = {76-86},
doi = {10.1016/j.ajo.2023.10.016},
pmid = {37890690},
issn = {1879-1891},
mesh = {Humans ; Beijing/epidemiology ; Prevalence ; Cross-Sectional Studies ; *Retinal Vein Occlusion ; *Glaucoma, Open-Angle ; Quality of Life ; China/epidemiology ; *Cataract ; *Peripheral Arterial Disease/diagnosis/epidemiology ; Glucose ; Risk Factors ; },
abstract = {PURPOSE: To explore the prevalence and associations of peripheral arterial disease (PAD) in China.<br><br>DESIGN: Population-based incidence estimate and cross-sectional study.<br><br>METHODS: The participants (n=3468) of the Beijing Eye Study underwent a detailed ophthalmologic and systemic examination including assessment of the ankle-brachial index (ABI). PAD was defined by an ABI of less than 0.9.<br><br>RESULTS: Blood pressure measurements of both arms and ankles were available for 1078 (31.1%) individuals. An ABI (mean: 1.09&#xb1;0.11; median: 1.10; range: 0.25, 1.36) of <0.9 and <0.95 was found in 32 of 1078 participants (3.0%, 95% CI 2.0, 4.0) and 70 of 1078 individuals (6.5%, 95% CI 5.0, 8.0), respectively. Higher PAD prevalence (multivariable analysis) was associated with older age (odds ratio [OR] 1.08, 95% CI 1.02, 1.15; P&#xa0;=&#xa0;.009), lower level of education (OR 0.62, 95% CI 0.43, 0.90; P&#xa0;=&#xa0;.01), lower quality of life (OR 0.67, 95% CI 1.11, 2.32), higher glucose serum concentration (OR 1.36, 95% CI 1.09, 1.58; P&#xa0;=&#xa0;.006), lower estimated glomerular filtration rate (OR 0.98, 95% CI 0.96, 0.99; P&#xa0;=&#xa0;.04), and higher prevalence of retinal vein occlusions (OR 7.30, 95% CI 1.63, 32.6; P&#xa0;=&#xa0;.009). PAD prevalence was not associated with the prevalence of glaucoma (P&#xa0;=&#xa0;.53) (open-angle glaucoma: P&#xa0;=&#xa0;.42; angle-closure glaucoma: P&#xa0;=&#xa0;.57) and age-related macular degeneration (any AMD: P&#xa0;=&#xa0;.39; early AMD: P&#xa0;=&#xa0;.31; intermediate AMD: P&#xa0;=&#xa0;.92; late AMD: P&#xa0;=&#xa0;.99), prevalence (P&#xa0;=&#xa0;.26) and stage (P&#xa0;=&#xa0;.07) of diabetic retinopathy, prevalence (P&#xa0;=&#xa0;.38) and degree (P&#xa0;=&#xa0;.68) of nuclear cataract, prevalence (P&#xa0;=&#xa0;.39) and degree (P&#xa0;=&#xa0;.72) of cortical cataract, prevalence of subcapsular cataract (P&#xa0;=&#xa0;.86), prevalence of pseudoexfoliation (P&#xa0;=&#xa0;.65), intraocular pressure (P&#xa0;=&#xa0;.50), axial length (P&#xa0;=&#xa0;.56), and peripapillary retinal nerve fiber layer thickness (P&#xa0;=&#xa0;.68).<br><br>CONCLUSIONS: The PAD prevalence (3.0%, 95% CI 2.0%, 4.0%) was relatively low in this cohort from rural and urban Beijing, with older age, lower educational level, lower quality of life, higher glucose serum concentration, lower estimated glomerular filtration rate, and higher prevalence of retinal vein occlusions as main associated factors.},
}
@article {pmid37890677,
year = {2024},
author = {Hagag, AM and Kaye, R and Hoang, V and Riedl, S and Anders, P and Stuart, B and Traber, G and Appenzeller-Herzog, C and Schmidt-Erfurth, U and Bogunovic, H and Scholl, HP and Prevost, T and Fritsche, L and Rueckert, D and Sivaprasad, S and Lotery, AJ},
title = {Systematic review of prognostic factors associated with progression to late age-related macular degeneration: Pinnacle study report 2.},
journal = {Survey of ophthalmology},
volume = {69},
number = {2},
pages = {165-172},
doi = {10.1016/j.survophthal.2023.10.010},
pmid = {37890677},
issn = {1879-3304},
mesh = {Humans ; *Disease Progression ; *Macular Degeneration/diagnosis ; Prognosis ; Risk Factors ; },
abstract = {There is a need to identify accurately prognostic factors that determine the progression of intermediate to late-stage age-related macular degeneration (AMD). Currently, clinicians cannot provide individualised prognoses of disease progression. Moreover, enriching clinical trials with rapid progressors may facilitate delivery of shorter intervention trials aimed at delaying or preventing progression to late AMD. Thus, we performed a systematic review to outline and assess the accuracy of reporting prognostic factors for the progression of intermediate to late AMD. A meta-analysis was originally planned. Synonyms of AMD and disease progression were used to search Medline and EMBASE for articles investigating AMD progression published between 1991 and 2021. Initial search results included 3229 articles. Predetermined eligibility criteria were employed to systematically screen papers by two reviewers working independently and in duplicate. Quality appraisal and data extraction were performed by a team of reviewers. Only 6 studies met the eligibility criteria. Based on these articles, exploratory prognostic factors for progression of intermediate to late AMD included phenotypic features (e.g. location and size of drusen), age, smoking status, ocular and systemic co-morbidities, race, and genotype. Overall, study heterogeneity precluded reporting by forest plots and meta-analysis. The most commonly reported prognostic factors were baseline drusen volume/size, which was associated with progression to neovascular AMD, and outer retinal thinning linked to progression to geographic atrophy. In conclusion, poor methodological quality of included studies warrants cautious interpretation of our findings. Rigorous studies are warranted to provide robust evidence in the future.},
}
@article {pmid37887425,
year = {2023},
author = {Greiner, JV and Glonek, T},
title = {Adenosine Triphosphate (ATP) and Protein Aggregation in Age-Related Vision-Threatening Ocular Diseases.},
journal = {Metabolites},
volume = {13},
number = {10},
pages = {},
pmid = {37887425},
issn = {2218-1989},
support = {EY-03988/EY/NEI NIH HHS/United States ; },
abstract = {Protein aggregation is the etiopathogenesis of the three most profound vision-threatening eye diseases: age-related cataract, presbyopia, and age-related macular degeneration. This perspective organizes known information on ATP and protein aggregation with a fundamental unrecognized function of ATP. With recognition that maintenance of protein solubility is related to the high intracellular concentration of ATP in cells, tissues, and organs, we hypothesize that (1) ATP serves a critical molecular function for organismal homeostasis of proteins and (2) the hydrotropic feature of ATP prevents pathological protein aggregation while assisting in the maintenance of protein solubility and cellular, tissue, and organismal function. As such, the metabolite ATP plays an extraordinarily important role in the prevention of protein aggregation in the leading causes of vision loss or blindness worldwide.},
}
@article {pmid37884703,
year = {2024},
author = {Corradetti, G and Rakocz, N and Chiang, JN and Avram, O and Alagorie, AR and Nittala, MG and Karamat, A and Boyer, DS and Sarraf, D and Halperin, E and Sadda, S},
title = {Prediction of activity in eyes with macular neovascularization due to age-related macular degeneration using deep learning.},
journal = {Eye (London, England)},
volume = {38},
number = {5},
pages = {819-821},
pmid = {37884703},
issn = {1476-5454},
mesh = {Humans ; *Deep Learning ; *Macular Degeneration ; Neovascularization, Pathologic ; Eye ; *Choroidal Neovascularization ; Fluorescein Angiography ; Tomography, Optical Coherence ; Retrospective Studies ; },
}
@article {pmid37883094,
year = {2023},
author = {Ren, C and Cui, H and Bao, X and Huang, L and He, S and Fong, HKW and Zhao, M},
title = {Proteopathy Linked to Exon-Skipping Isoform of RGR-Opsin Contributes to the Pathogenesis of Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {13},
pages = {41},
pmid = {37883094},
issn = {1552-5783},
mesh = {Animals ; Humans ; Mice ; Exons ; *Macular Degeneration/genetics ; Opsins ; Protein Isoforms ; Retina ; *Receptors, G-Protein-Coupled/genetics ; *Eye Proteins/genetics ; },
abstract = {PURPOSE: Proteopathy is believed to contribute to age-related macular degeneration (AMD). Much research indicates that AMD begins in the retinal pigment epithelium (RPE), which is associated with formation of extracellular drusen, a clinical hallmark of AMD. Human RPE produces a drusen-associated abnormal protein, the exon Ⅵ-skipping splice isoform of retinal G protein-coupled receptor (RGR-d). In this study, we investigate the detrimental effects of RGR-d on cultured cells and mouse retina.<br><br>METHODS: ARPE-19 cells were stably infected by lentivirus overexpressing RGR or RGR-d and were treated with MG132, sometimes combined with or without endoplasmic reticulum (ER) stress inducer, tunicamycin. RGR and RGR-d protein expression, degeneration pathway, and potential cytotoxicity were explored. Homozygous RGR-d mice aged 8 or 14&#xa0;months were fed with a high-fat diet for 3&#xa0;months and then subjected to ocular examination and histopathology experiments.<br><br>RESULTS: We confirm that RGR-d is proteotoxic under various conditions. In ARPE-19 cells, RGR-d is misfolded and almost completely degraded via the ubiquitin-proteasome system. Unlike normal RGR, RGR-d increases ER stress, triggers the unfolded protein response, and exerts potent cytotoxicity. Aged RGR-d mice manifest disrupted RPE cell integrity, apoptotic photoreceptors, choroidal deposition of complement C3, and CD86+CD32+ proinflammatory cell infiltration into retina and RPE-choroid. Furthermore, the AMD-like phenotype of RGR-d mice can be aggravated by a high-fat diet.<br><br>CONCLUSIONS: Our study confirmed the pathogenicity of the RGR splice isoform and corroborated a significant role of proteopathy in AMD. These findings may contribute to greater comprehension of the multifactorial causes of AMD.},
}
@article {pmid37881631,
year = {2023},
author = {Yang, H and Li, Z and Jin, W and Yang, A},
title = {Application progress of human amniotic membrane in vitreoretinopathy: a literature review.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1206577},
pmid = {37881631},
issn = {2296-858X},
abstract = {Recently, the application of the amniotic membrane (AM) in ophthalmology is gradually expanding from the anterior to the posterior segment of the eye. Its characteristics of anti-inflammation, anti-bacterial, anti-vascularization, immune regulation, anti-fibrosis, pro-epithelialization, and so forth have made it a hot topic in ophthalmic research. AM has been confirmed to repair photoreceptors, restore normal retinal structures, and close the abnormal structures in the optic disc. Currently, the application areas mainly include retinal hole, retinal detachment, optic disc pit, retinal degenerative diseases, and choroidal hole. This article reviews the current literature applying AM transplantation in the treatment of various posterior segment diseases while comparing the clinical outcomes with other techniques.},
}
@article {pmid37880219,
year = {2023},
author = {Henning, Y and Willbrand, K and Larafa, S and Weißenberg, G and Matschke, V and Theiss, C and Görtz, GE and Matschke, J},
title = {Cigarette smoke causes a bioenergetic crisis in RPE cells involving the downregulation of HIF-1α under normoxia.},
journal = {Cell death discovery},
volume = {9},
number = {1},
pages = {398},
pmid = {37880219},
issn = {2058-7716},
support = {860245//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Sk&#x142;odowska-Curie Actions (H2020 Excellent Science - Marie Sk&#x142;odowska-Curie Actions)/ ; 02NUK061B//Bundesministerium f&#xfc;r Bildung und Forschung (Federal Ministry of Education and Research)/ ; },
abstract = {Age-related macular degeneration (AMD) is the most common blinding disease in the elderly population. However, there are still many uncertainties regarding the pathophysiology at the molecular level. Currently, impaired energy metabolism in retinal pigment epithelium (RPE) cells is discussed as one major hallmark of early AMD pathophysiology. Hypoxia-inducible factors (HIFs) are important modulators of mitochondrial function. Moreover, smoking is the most important modifiable risk factor for AMD and is known to impair mitochondrial integrity. Therefore, our aim was to establish a cell-based assay that enables us to investigate how smoking affects mitochondrial function in conjunction with HIF signaling in RPE cells. For this purpose, we treated a human RPE cell line with cigarette smoke extract (CSE) under normoxia (21% O2), hypoxia (1% O2), or by co-treatment with Roxadustat, a clinically approved HIF stabilizer. CSE treatment impaired mitochondrial integrity, involving increased mitochondrial reactive oxygen species, disruption of mitochondrial membrane potential, and altered mitochondrial morphology. Treatment effects on cell metabolism were analyzed using a Seahorse Bioanalyzer. Mitochondrial respiration and ATP production were impaired in CSE-treated cells under normoxia. Surprisingly, CSE-treated RPE cells also exhibited decreased glycolytic rate under normoxia, causing a bioenergetic crisis, because two major metabolic pathways that provide ATP were impaired by CSE. Downregulation of glycolytic rate was HIF-dependent because HIF-1α, the α-subunit of HIF-1, was downregulated by CSE on the protein level, especially under normoxia. Moreover, hypoxia incubation and treatment with Roxadustat restored glycolytic flux. Taken together, our in vitro model provides interesting insights into HIF-dependent regulation of glycolysis under normoxic conditions, which will enable us to investigate signaling pathways involved in RPE metabolism in health and disease.},
}
@article {pmid37879537,
year = {2024},
author = {Blinder, KJ and Calhoun, C and Maguire, MG and Glassman, AR and Mein, CE and Baskin, DE and Vieyra, G and Jampol, LM and Chica, MA and Sun, JK and Martin, DF and , },
title = {Home OCT Imaging for Newly Diagnosed Neovascular Age-Related Macular Degeneration: A Feasibility Study.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {4},
pages = {376-387},
pmid = {37879537},
issn = {2468-6530},
support = {U10 EY014231/EY/NEI NIH HHS/United States ; UG1 EY014231/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Feasibility Studies ; Retina ; Visual Acuity ; *Macular Degeneration/diagnosis ; },
abstract = {OBJECTIVE: To assess the feasibility of daily Home OCT imaging among patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Prospective observational study.<br><br>PARTICIPANTS: Participants with &#x2265; 1 eye with previously untreated nAMD and visual acuity 20/20 to 20/320.<br><br>METHODS: Participants meeting the ocular eligibility criteria were considered for enrollment; those who provided consent received a Notal Vision Home OCT device. Participants were instructed to scan both eyes daily. Retina specialists managed treatment according to their standard practice, without access to the Home OCT data. The presence of fluid detected by a reading center (RC) from in-office OCT scans was compared with fluid volumes measured by the Notal OCT Analyzer (NOA) on Home OCT images.<br><br>MAIN OUTCOME MEASURES: Proportion of participants meeting ocular eligibility criteria who participated in daily scanning, frequency and duration of scanning, proportion of scans eligible for fluid quantification, participant experience with the device, agreement between the RC and NOA fluid determinations, and characteristics of fluid dynamics.<br><br>RESULTS: Among 40 participants meeting ocular eligibility criteria, 14 (35%) initiated self-scanning. Planned travel (n&#xa0;= 7, 17.5%) and patient-reported inadequate cell reception for the upload of images (n&#xa0;= 5, 12.5%) were the most frequent reasons for not participating. Considering scans of the study eye only, the mean (standard deviation) was 6.3 (0.6) for weekly scanning frequency and 47 (17) seconds for scan duration per eye. Among 2304 scans, 86.5% were eligible for fluid quantification. All participants agreed that scanning became easier over time, and only 1 did not want to continue daily scanning. For 35 scan pairs judged as having fluid by in-office OCT, the NOA detected fluid on 31 scans (89%). For 14 scan pairs judged as having no fluid on in-office OCT, the NOA did not detect fluid on 10 scans (71%). Daily fluid patterns after treatment initiation varied considerably between patients.<br><br>CONCLUSIONS: For patients with nAMD who initiated home scanning, frequency and quality of scanning and accuracy of fluid detection were sufficient to assess the monitoring of fluid at home. Accommodations for travel and Wi-Fi connectivity could improve uptake of the Home OCT device.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37878301,
year = {2023},
author = {Voigt, AP and Mullin, NK and Navratil, EM and Flamme-Wiese, MJ and Lin, LC and Scheetz, TE and Han, IC and Stone, EM and Tucker, BA and Mullins, RF},
title = {Gene Expression Within a Human Choroidal Neovascular Membrane Using Spatial Transcriptomics.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {13},
pages = {40},
pmid = {37878301},
issn = {1552-5783},
support = {F30 EY034009/EY/NEI NIH HHS/United States ; T32 GM145441/GM/NIGMS NIH HHS/United States ; T32 GM139776/GM/NIGMS NIH HHS/United States ; P30 EY025580/EY/NEI NIH HHS/United States ; F30 EY031923/EY/NEI NIH HHS/United States ; R01 EY033331/EY/NEI NIH HHS/United States ; R01 EY033308/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Animals ; Mice ; Transcriptome ; Endothelial Cells ; *Choroidal Neovascularization/genetics ; Retina ; *Macular Degeneration/genetics ; },
abstract = {PURPOSE: Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process.<br><br>METHODS: To study how gene expression is altered in focal areas of pathology, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We performed differential expression to identify genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes.<br><br>RESULTS: Within the area of neovascularization, endothelial cells demonstrated increased expression of genes related to Rho family GTPase signaling and integrin signaling. Likewise, VEGF and TGFB1 were identified as potential upstream regulators that could drive the observed gene expression changes produced by endothelial and retinal pigment epithelium cells in the macular neovascularization donor. These spatial gene expression profiles were compared to previous single-cell gene expression experiments in human age-related macular degeneration as well as a model of laser-induced neovascularization in mice. As a secondary aim, we investigated regional gene expression patterns within the macular neural retina and between the macular and peripheral choroid.<br><br>CONCLUSIONS: Overall, this study spatially analyzes gene expression across the retina, retinal pigment epithelium, and choroid in health and describes a set of candidate molecules that become dysregulated in macular neovascularization.},
}
@article {pmid37878215,
year = {2024},
author = {Castro, BFM and Steel, JC and Layton, CJ},
title = {AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.},
journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy},
volume = {38},
number = {1},
pages = {73-93},
pmid = {37878215},
issn = {1179-190X},
mesh = {Humans ; *Diabetic Retinopathy/therapy/drug therapy ; Dependovirus/genetics ; *Choroidal Neovascularization/drug therapy/genetics ; *Macular Degeneration/therapy/drug therapy ; Gene Transfer Techniques ; *Diabetes Mellitus ; },
abstract = {Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vascular diseases with high prevalence, ranking among the leading causes of blindness and vision loss worldwide. Despite being effective, current treatments for AMD and DR are burdensome for patients and clinicians, resulting in suboptimal compliance and real risk of vision loss. Thus, there is an unmet need for long-lasting alternatives with improved safety and efficacy. Adeno-associated virus (AAV) is the leading vector for ocular gene delivery, given its ability to enable long-term expression while eliciting relatively mild immune responses. Progress has been made in AAV-based gene therapies for not only inherited retinal diseases but also acquired conditions with preclinical and clinical studies of AMD and DR showing promising results. These studies have explored several pathways involved in the disease pathogenesis, as well as different strategies to optimise gene delivery. These include engineered capsids with enhanced tropism to particular cell types, and expression cassettes incorporating elements for a targeted and controlled expression. Multiple-acting constructs have also been investigated, in addition to gene silencing and editing. Here, we provide an overview of strategies employing AAV-mediated gene delivery to treat AMD and DR. We discuss preclinical efficacy studies and present the latest data from clinical trials for both diseases.},
}
@article {pmid37876508,
year = {2023},
author = {Prahs, P and Brandl, C and Helbig, H and Volz, C},
title = {Baseline characteristics and progression of neovascular age-related macular degeneration in patients receiving over 60 intravitreal injections of anti-vascular endothelial growth factor.},
journal = {Romanian journal of ophthalmology},
volume = {67},
number = {3},
pages = {260-266},
pmid = {37876508},
issn = {2501-2533},
mesh = {Humans ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Intravitreal Injections ; Ranibizumab ; *Macular Degeneration/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {Objective: Age-related macular degeneration (AMD) is the leading cause of vision loss in older populations of industrialized countries. Antibody-based therapy inhibiting the vascular endothelial growth factor (VEGF) has been very successful in the treatment of the neovascular form of AMD. This retrospective clinical study investigates the baseline characteristics and progression of neovascular age-related macular degeneration (nAMD) in patients who received over 60 anti-VEGF intravitreal injections. Methods: Retrospective analysis of 6812 eyes of 5678 patients undergoing anti-VEGF treatment at our clinic between November 2006 and December 2017 yielded 12 eyes of 12 patients who had received more than 60 intravitreal injections into one eye. We re-evaluated the baseline characteristics of visual acuity, intraocular pressure, optical coherence tomography, fluorescein angiography, as well as autofluorescence and analyzed the documented disease progress as monitored in our daily clinical practice. Data on the fellow eye were also analyzed. Results: Each of our 12 patients had the injected anti-VEGF agent (bevacizumab, ranibizumab, or aflibercept) changed at least once during treatment. After initial improvement, visual acuity decreased in most patients over time. The 2 patients with the best visual acuity at the beginning also showed the best visual acuity at the end of the study. No significant change was observed in the intraocular pressure. Conclusions: After the initial improvement, visual acuity decreased over time. Good visual acuity at the beginning of the study increased the chances of maintaining the same level throughout the treatment. Intravitreal treatment did not affect intraocular pressure. Abbreviations: AMD = age-related macular degeneration, nAMD = neovascular age-related macular degeneration, VEGF = vascular endothelial growth factor, OCT = optical coherence tomography, VA = visual acuity, PDT = photodynamic therapy.},
}
@article {pmid37876505,
year = {2023},
author = {Popescu Patoni, SI and Muşat, AAM and Patoni, C and Popescu, MN and Munteanu, M and Costache, IB and Pîrvulescu, RA and Mușat, O},
title = {Artificial intelligence in ophthalmology.},
journal = {Romanian journal of ophthalmology},
volume = {67},
number = {3},
pages = {207-213},
pmid = {37876505},
issn = {2501-2533},
mesh = {Infant, Newborn ; Humans ; Artificial Intelligence ; *Ophthalmology ; *Diabetic Retinopathy/diagnosis ; Vascular Endothelial Growth Factor A ; *Retinal Perforations ; *Glaucoma/diagnosis ; *Macular Degeneration ; },
abstract = {One of the fields of medicine in which artificial intelligence techniques have made progress is ophthalmology. Artificial intelligence (A.I.) applications for preventing vision loss in eye illnesses have developed quickly. Artificial intelligence uses computer programs to execute various activities while mimicking human thought. Machine learning techniques are frequently utilized in the field of ophthalmology. Ophthalmology holds great promise for advancing artificial intelligence, thanks to various digital methods like optical coherence tomography (OCT) and visual field testing. Artificial intelligence has been used in ophthalmology to treat eye conditions impairing vision, including macular holes (M.H.), age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts. The more common occurrence of these diseases has led to artificial intelligence development. It is important to get annual screenings to detect eye diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration. These conditions can cause decreased visual acuity, and it is necessary to identify any changes or progression in the disease to receive appropriate treatment. Numerous studies have been conducted based on artificial intelligence using different algorithms to improve and simplify current medical practice and for early detection of eye diseases to prevent vision loss. Abbreviations: AI = artificial intelligence, AMD = age-related macular degeneration, ANN = artificial neural networks, AAO = American Academy of Ophthalmology, CNN = convolutional neural network, DL = deep learning, DVP = deep vascular plexus, FDA = Food and Drug Administration, GCL = ganglion cell layer, IDP = Iowa Detection Program, ML = Machine learning techniques, MH = macular holes, MTANN = massive training of the artificial neural network, NLP = natural language processing methods, OCT = optical coherence tomography, RBS = Radial Basis Function, RNFL = nerve fiber layer, ROP = Retinopathy of Prematurity, SAP = standard automated perimetry, SVP = Superficial vascular plexus, U.S. = United States, VEGF = vascular endothelial growth factor.},
}
@article {pmid37875865,
year = {2023},
author = {Hollitt, GL and Qassim, A and Thomson, D and Schmidt, JM and Nguyen, TT and Landers, J and MacGregor, S and Siggs, OM and Souzeau, E and Craig, JE},
title = {Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {431},
pmid = {37875865},
issn = {1471-2415},
mesh = {Humans ; Middle Aged ; Prospective Studies ; Multifactorial Inheritance ; Australia ; *Glaucoma/diagnosis/genetics/epidemiology ; Risk Factors ; Risk Assessment ; *Macular Degeneration/diagnosis/genetics/epidemiology ; },
abstract = {BACKGROUND: Glaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic risk scores (PRS) allow for cost-effective broad population risk stratification for these conditions. The predictive potential of PRS could facilitate earlier diagnosis and treatment, and prevent unnecessary vision loss.<br><br>METHODS: The Genetic Risk Assessment of Degenerative Eye disease (GRADE) study is a prospective study designed to generate high-quality evidence about the feasibility of PRS to stratify individuals from the general population, enabling identification of those at highest risk of developing glaucoma or AMD. The targeted recruitment is 1000 individuals aged over 50 years, from which blood or saliva samples will be used for genotyping and an individual PRS for glaucoma and AMD will be derived. Individuals with PRS values in the bottom decile (n&#x2009;=&#x2009;100), top decile (n&#x2009;=&#x2009;100) and middle 80% (n&#x2009;=&#x2009;100) for both glaucoma and AMD will undergo a detailed eye examination for glaucoma and/or AMD.<br><br>DISCUSSION: The primary objective will be to compare the prevalence of glaucoma and AMD cases between low, intermediate, and high PRS risk groups. We expect to find a higher prevalence of both diseases in the high PRS risk group, as compared to the middle and low risk groups. This prospective study will assess the clinical validity of a PRS for glaucoma and AMD in the general Australian population. Positive findings will support the implementation of PRS into clinical practice.},
}
@article {pmid37873318,
year = {2023},
author = {Guo, S and Liu, X and Cheng, X and Jiang, Y and Ji, S and Liang, Q and Koval, A and Li, Y and Owen, LA and Kim, IK and Aparicio, A and Shen, JP and Kopetz, S and Weinstein, JN and DeAngelis, MM and Chen, R and Wang, W},
title = {DeMixSC: a deconvolution framework that uses single-cell sequencing plus a small benchmark dataset for improved analysis of cell-type ratios in complex tissue samples.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37873318},
issn = {2692-8205},
support = {S10 OD018033/OD/NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA268380/CA/NCI NIH HHS/United States ; S10 OD023469/OD/NIH HHS/United States ; P30 EY002520/EY/NEI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; S10 OD025240/OD/NIH HHS/United States ; R01 CA239342/CA/NCI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; R01 EY022356/EY/NEI NIH HHS/United States ; K22 CA234406/CA/NCI NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 EY018571/EY/NEI NIH HHS/United States ; },
abstract = {Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we introduce an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using the better-matched, i.e., benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using a benchmark dataset of healthy retinas suggest much-improved deconvolution accuracy. Further analysis of a cohort of 453 patients with age-related macular degeneration supports the broad applicability of DeMixSC. Our findings reveal the impact of technological discrepancy on deconvolution performance and underscore the importance of a well-matched dataset to resolve this challenge. The developed DeMixSC framework is generally applicable for deconvolving large cohorts of disease tissues, and potentially cancer.},
}
@article {pmid37873056,
year = {2023},
author = {Vishwakarma, S and Borkar, DS and LaPrise, A and Mbagwu, M and Leng, T},
title = {Vitreoretinal Specialist Use of Ancillary Testing: An IRIS[®] Registry Analysis.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {3077-3085},
pmid = {37873056},
issn = {1177-5467},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To investigate patterns of ancillary imaging testing among vitreoretinal specialists for patients with vitreoretinal disease in the United States (US).<br><br>METHODS: Optical coherence tomography (OCT), color fundus photography (CFP), and fluorescein angiography (FA), ordered by vitreoretinal specialists and documented within the American Academy of Ophthalmology IRIS[&#xae;] Registry (Intelligent Research in Sight) between 01 January 2018 and 31 December 2020, were retrospectively assessed. Trends in imaging modality choice were analyzed by payer type, geographic region, and practice type. Sub-analyses were conducted according to categorization of vitreoretinal specialists into those treating a high versus low volume of patients with neovascular age-related macular degeneration (nAMD).<br><br>RESULTS: OCT was the most common imaging modality used, followed by CFP and FA. Following normalization, the highest volume of OCT procedures performed were identified among Medicare Advantage and Medicare Fee-for-Service beneficiaries, within the South of the US, and at medium and large practices. Minimal differences were observed for CFP and FA volume across payer types and regions. Across practice types, the largest volume of CFP and FA procedures were identified in small and private equity owned practices, respectively. Vitreoretinal specialists with a high nAMD volume more frequently performed OCT than those with a low nAMD volume.<br><br>CONCLUSION: Vitreoretinal specialists demonstrated a strong preference for OCT, with real-world associations according to payer type, geographic location, and practice type. Volume of nAMD patients seen impacted the likelihood of specialists ordering OCTs.},
}
@article {pmid37871984,
year = {2023},
author = {Airaldi, M and Invernizzi, A and Nguyen, V and Vujosevic, S and Ricci, F and Monaco, P and Nassisi, M and Barthelmes, D and Gillies, M and Viola, F},
title = {Twenty-four-month real-life treatment outcomes of polypoidal choroidal vasculopathy versus type 1 macular neovascularization in Caucasians.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {51},
number = {8},
pages = {799-807},
doi = {10.1111/ceo.14305},
pmid = {37871984},
issn = {1442-9071},
support = {634/2019//Novartis/ ; },
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Polypoidal Choroidal Vasculopathy ; Retrospective Studies ; *Choroidal Neovascularization/diagnosis/drug therapy ; Fluorescein Angiography ; Treatment Outcome ; Intravitreal Injections ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: To compare 24-month real-world outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population.<br><br>METHODS: Retrospective analysis from a prospectively designed observational database. Data from Italian centres participating in the Fight Retinal Blindness! (FRB!) project were collected. Treatment-na&#xef;ve PCV or type 1 MNV commencing treatment after January 2009 were included. The primary outcome was 24-month visual acuity (VA) change; other outcomes included baseline characteristics, number of anti-VEGF injections, time to lesion inactivation and proportion of active visits.<br><br>RESULTS: A total of 322 eyes (114 PCVs) from 291 patients were included. Median [Q1, Q3] VA at baseline was comparable (70 [55, 75.8] vs. 70 [58.8, 75] letters, p&#x2009;=&#x2009;0.95). Adjusted VA change at 2&#x2009;years was higher in PCV (mean [95% CI], +1.2 [-1.6, 4.1] vs. -3.6 [-6, -1.2] letters, p&#x2009;=&#x2009;0.005). PCV received fewer anti-VEGF injections over the first 24&#x2009;months of treatment than type 1 MNV (median [Q1, Q3], 8 [5, 10] vs. 9 [7, 12.2] injections, p&#x2009;=&#x2009;0.001), inactivated earlier (median [Q1, Q3], 235 [184, 308] vs. 252 [169, 343]&#x2009;days, p&#x2009;=&#x2009;0.04) and was less frequently graded 'active' (62% vs. 68% of visits, p&#x2009;=&#x2009;0.001).<br><br>CONCLUSIONS: PCV had slightly better VA outcomes over 24&#x2009;months of treatment than type 1 MNV after receiving less anti-VEGF injections. These results suggest a possible overlap of the two clinical entities with similar visual prognosis in Caucasians.},
}
@article {pmid37871680,
year = {2024},
author = {Mahmoudi, A and Corradetti, G and Emamverdi, M and Lindenberg, S and He, Y and Oncel, D and Santina, A and Baek, J and Kadomoto, S and Nittala, MG and Sadda, SR},
title = {Atrophic Lesions Associated with Age-Related Macular Degeneration: High-Resolution versus Standard OCT.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {4},
pages = {367-375},
doi = {10.1016/j.oret.2023.10.011},
pmid = {37871680},
issn = {2468-6530},
mesh = {Humans ; Tomography, Optical Coherence/methods ; Prospective Studies ; Cross-Sectional Studies ; Reproducibility of Results ; *Macular Degeneration/complications ; Atrophy ; *Connective Tissue Diseases ; },
abstract = {OBJECTIVE: The objective of this study was to determine whether high-resolution OCT (HR-OCT) could enhance the identification and classification of atrophic features in age-related macular degeneration (AMD) compared with standard resolution OCT.<br><br>DESIGN: Prospective, observational, cross-sectional study.<br><br>SUBJECTS: The study included 60 eyes from 60 patients > 60 years of age with a diagnosis of AMD.<br><br>METHODS: The participants underwent volume OCT scanning using HR-OCT and standard resolution OCT devices. Trained graders reviewed and graded the scans, identifying specific regions of interest for subsequent analysis.<br><br>MAIN OUTCOME MEASURES: The study focused on identifying and classifying complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA), incomplete RORA (iRORA), and other nonatrophic AMD features. Additionally, qualitative and quantitative features associated with atrophy were assessed.<br><br>RESULTS: The agreement among readers for classifying atrophic lesions was substantial to perfect for both HR-OCT (0.88) and standard resolution OCT(0.82). However, HR-OCT showed a higher accuracy in identifying iRORA lesions compared with standard OCT. Qualitative assessment of features demonstrated higher agreement for HR-OCT, particularly in identifying external limiting membrane (ELM) (0.95) and ellipsoid zone (EZ) disruption (0.94). Quantitative measurements of features such as hypertransmission defects, RPE attenuation/disruption, EZ disruption width, and ELM disruption width showed excellent interreader agreement with HR-OCT (> 0.90 for all features) but only moderate agreement with standard OCT (0.51-0.60).<br><br>CONCLUSIONS: The study results suggest that HR-OCT improves the accuracy and reliability of classifying and quantifying atrophic lesions associated with AMD compared with standard resolution OCT. The quantitative findings in particular may have implications for future research and clinical practice, especially with the availability of therapeutic agents for treating geographic atrophy and the development of commercially available HR-OCT devices.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37871271,
year = {2023},
author = {Berlin, A and Messinger, JD and Ramtohul, P and Balaratnasingam, C and Mendis, R and Ferrara, D and Freund, KB and Curcio, CA},
title = {INFLAMMATORY CELL ACTIVITY IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Histologic Case Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {11},
pages = {1904-1913},
pmid = {37871271},
issn = {1539-2864},
support = {R01 EY006109/EY/NEI NIH HHS/United States ; },
mesh = {Female ; Humans ; *Choroidal Neovascularization/diagnosis/drug therapy/complications ; Fluorescein Angiography ; *Geographic Atrophy/diagnosis/drug therapy/complications ; *Macular Degeneration/complications ; *Retinal Drusen/etiology ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence/methods ; Aged, 80 and over ; },
abstract = {BACKGROUND: Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration.<br><br>METHODS: Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes.<br><br>RESULTS: Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells.<br><br>CONCLUSION: Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.},
}
@article {pmid37871227,
year = {2023},
author = {Wang, K and Lyu, Y and Tschulakow, AV and Brash, DE and Schraermeyer, U},
title = {Reply to Pfeffer: Macular degeneration clues from comparative anatomy.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {44},
pages = {e2315582120},
pmid = {37871227},
issn = {1091-6490},
support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Anatomy, Comparative ; *Macular Degeneration ; },
}
@article {pmid37870012,
year = {2023},
author = {Gorhe, S and Chugh, MK and Goel, N and D'Souza, Z and Saurabh, K and Roy, R},
title = {Clinical feature of cystoid macular degeneration in central serous chorioretinopathy.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {11},
pages = {3489-3493},
pmid = {37870012},
issn = {1998-3689},
mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; *Central Serous Chorioretinopathy/complications/diagnosis ; Retrospective Studies ; *Macular Degeneration/complications ; Choroid ; Tomography, Optical Coherence/methods ; *Retinal Neovascularization/complications ; },
abstract = {PURPOSE: Cystoid macular degeneration (CMD) is a feature of chronic central serous chorioretinopathy (CSCR). Present study intended to analyze the clinical presentation, risk factors, choroidal features, and outcome of CMD in CSCR.<br><br>METHODS: This was a retrospective, record-based descriptive study, which included chronic CSCR eyes with CMD. Demographic profile and clinical history were obtained from medical records. Spectralis spectral domain optical coherence tomography (SDOCT; Heidelberg Engineering,Germany) was used for acquiring SDOCT images and for performing fluorescein angiography , indocyanine green angiography , and optical coherence tomography (OCT) angiography.<br><br>RESULTS: The study included 101 eyes of 69 consecutive patients of CSCR having CMD. The mean age of patients was 56 &#xb1; 9.4 years (range 40-79 years), and majority (63, 91.3%) of the patients were male. Prior history of corticosteroid use was present in seven (10.1%) patients. Mean time interval between the first diagnosis of CSCR and appearance of CMD was 55.3 &#xb1; 33.9 months. CMD was located away from the fovea in majority of eyes (68, 67.3%). Mean subfoveal choroidal thickness was 396.71 &#xb1; 90.5 &#x3bc;m. Subretinal pigment epithelium choroidal neovascularization was noted in four (3.96%) eyes.<br><br>CONCLUSION: CMD appears as a late complication of CSCR and is usually present away from the fovea. Such eyes had thickened choroid and fewer cases had associated choroidal neovascularization. Further comparative studies would be needed to validate these findings.},
}
@article {pmid37869030,
year = {2024},
author = {Chang, DS and Callaway, NF and Steffen, V and Csaky, K and Guymer, RH and Birch, DG and Patel, PJ and Ip, M and Gao, SS and Briggs, J and Honigberg, L and Lai, P and Ferrara, D and Sepah, YJ},
title = {Macular Sensitivity Endpoints in Geographic Atrophy: Exploratory Analysis of Chroma and Spectri Clinical Trials.},
journal = {Ophthalmology science},
volume = {4},
number = {1},
pages = {100351},
pmid = {37869030},
issn = {2666-9145},
abstract = {PURPOSE: To assess different microperimetry (MP) macular sensitivity outcome measures capturing functional deterioration in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>DESIGN: Patients were included from 2 identically designed, phase III, double-masked, randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531).<br><br>PARTICIPANTS: Patients enrolled were aged &#x2265; 50 years with bilateral GA and no evidence of previous or active neovascular AMD.<br><br>METHODS: Patients were randomized 2:1:2:1 to receive through 96 weeks intravitreal lampalizumab 10 mg every 4 weeks (LQ4W), every 6 weeks (LQ6W), or corresponding sham procedures. For this study, mesopic macular sensitivity of the central 20&#xb0; was assessed using MP-1 microperimeter at selected sites.<br><br>MAIN OUTCOME MEASURES: Two exploratory endpoints were developed, namely perilesional sensitivity (average of points adjacent to absolute scotomatous points) and responding sensitivity (average of all nonscotomatous points; > 0 dB at baseline) by using customized masks for each patient. These were compared with conventional MP endpoints (mean macular sensitivity and number of absolute scotomatous points).<br><br>RESULTS: Of 1881 Chroma and Spectri participants, 277 agreed to participate in the present study. Of these, 197 (LQ4W, n&#xa0;=&#xa0;63; LQ6W, n&#xa0;=&#xa0;68; pooled sham, n&#xa0;=&#xa0;66) had reliable MP results. Enlargement of GA lesion area by approximately 2 mm[2]/year across treatment groups was accompanied by deterioration in all MP parameters. There was no difference in worsening of macular sensitivity or absolute scotomatous points among treatment groups. Perilesional and responding sensitivities showed greater decline over time than mean macular sensitivity. Change in GA lesion area at week 48 showed better correlation with perilesional sensitivity (r&#xa0;=&#xa0;-0.17) and responding sensitivity (r&#xa0;=&#xa0;-0.20) than mean macular sensitivity (r&#xa0;=&#xa0;-0.03), while the correlation was highest with the number of absolute scotomatous points (r&#xa0;=&#xa0;0.37).<br><br>CONCLUSIONS: Perilesional or responding macular sensitivity measured by MP should be considered more sensitive endpoints than mean macular sensitivity for monitoring functional decline over time in GA. Although perilesional, responding, and mean macular sensitivity had weak correlation with GA lesion area, the number of absolute scotomatous points may provide additional information on the anatomic/functional correlation.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37869027,
year = {2024},
author = {Li, B and Goss, D and Miller, JW and Lin, JB and Vavvas, DG},
title = {Systemic Dyslipidemia in Age-related Macular Degeneration: An Updated Systematic Review and Meta-analysis.},
journal = {Ophthalmology science},
volume = {4},
number = {1},
pages = {100341},
pmid = {37869027},
issn = {2666-9145},
abstract = {TOPIC: Though lipid and cholesterol dyshomeostasis is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), there is no consensus regarding which elements of systemic lipid homeostasis are perturbed in AMD. In this systematic review and meta-analysis, an update to that performed by Wang et al in 2016, we characterized serum lipoprotein profiles in patients with AMD and its various stages.<br><br>CLINICAL RELEVANCE: These findings may identify novel therapeutic approaches for AMD, a leading cause of blindness among older adults in the industrialized world.<br><br>METHODS: We used MEDLINE, Embase, and Web of Science to identify articles from database inception to May 2022 that reported blood/serum levels of lipid subspecies (triglycerides [TGs], total cholesterol [TC], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) in patients with AMD compared with controls. We meta-analyzed the data by generating multilevel random-effects models using restricted maximum likelihood estimation.<br><br>RESULTS: Our updated meta-analysis included 56 studies, almost 3 times as many studies as the 2016 meta-analysis with a total of 308&#x2009;188 participants. There were no significant differences in serum TG, TC, LDL, or HDL between patients with AMD and non-AMD controls. Given significant heterogeneity, we performed subanalyses specifically in patients with early to intermediate nonexudative AMD, advanced nonexudative AMD, and advanced exudative AMD. Compared with non-AMD controls, patients with early to intermediate nonexudative AMD had significantly lower serum TG (standardized mean difference [SMD]:&#xa0;-0.03; 95% confidence interval [95% CI]:&#xa0;-0.06 to&#xa0;-0.01) and higher serum HDL (SMD: 0.07; 95% CI: 0.04-0.11). Patients with advanced exudative AMD had significantly higher serum LDL (SMD: 0.33; 95% CI: 0.04-0.62) compared with non-AMD controls. There were no other significant differences identified.<br><br>CONCLUSION: We found that there is significant heterogeneity in systemic lipoproteins in patients with AMD compared with non-AMD controls. The specific pattern of lipid dyshomeostasis appeared to be distinct based on AMD stage. These findings highlight both the underlying heterogeneity of AMD as well as the presence of distinct pathophysiological mechanisms involved at different stages or subtypes of AMD and may inform the development of novel therapeutic approaches.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37869026,
year = {2024},
author = {Lains, I and Han, X and Gil, J and Providencia, J and Nigalye, A and Alvarez, R and Douglas, VP and Mendez, K and Katz, R and Tsougranis, G and Li, J and Kelly, RS and Kim, IK and Lasky-Su, J and Silva, R and Miller, JW and Liang, L and Vavvas, D and Miller, JB and Husain, D},
title = {Plasma Metabolites Associated with OCT Features of Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {1},
pages = {100357},
pmid = {37869026},
issn = {2666-9145},
support = {K01 HL146980/HL/NHLBI NIH HHS/United States ; R01 EY030088/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD.<br><br>DESIGN: Prospectively designed, cross-sectional study.<br><br>PARTICIPANTS: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal.<br><br>METHODS: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons.<br><br>MAIN OUTCOME MEASURES: Plasma metabolite levels associated with OCT features.<br><br>RESULTS: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed.<br><br>CONCLUSIONS: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37869023,
year = {2024},
author = {Grewal, DS and Wykoff, CC and D'Souza, D and Jehl, V and Alecu, I and Jaffe, GJ},
title = {Imaging Features of Retinal Vasculitis and/or Retinal Vascular Occlusion after Brolucizumab Treatment in the Postmarketing Setting.},
journal = {Ophthalmology science},
volume = {4},
number = {1},
pages = {100361},
pmid = {37869023},
issn = {2666-9145},
abstract = {PURPOSE: The aim of this analysis was to characterize the spectrum of inflammatory changes arising from brolucizumab use in routine clinical practice.<br><br>DESIGN: Retrospective analysis of fluorescein angiography (FA), fundus photography (FP) and OCT images taken at the time of adverse event.<br><br>SUBJECTS: Brolucizumab-treated patients with neovascular age-related macular degeneration with retinal vasculitis (RV) and/or retinal vascular occlusion (RO) reported to Novartis Patient Safety between February 2020 and January&#xa0;2021.<br><br>METHODS: Ocular images were reviewed by an external reading center using predefined grading lists for FA, FP, and OCT.<br><br>MAIN OUTCOME MEASURES: Classification of images, the most common imaging features of RV and/or RO by each imaging modality, and the anatomical location of the adverse event in relation to the macula.<br><br>RESULTS: Gradable images (N&#xa0;= 475; 222 eyes; 198 patients) were classified as RV only (n&#xa0;= 72); RO only (n&#xa0;=&#xa0;9), RV&#xa0;+ RO (n&#xa0;= 63); posterior segment intraocular inflammation (n&#xa0;= 31); or none by imaging (n&#xa0;= 47). Of the 144 eyes with RV and/or RO, the most common imaging features were vascular leakage on FA, perivascular sheathing on FP, and hyperreflective dots in the vitreous humor on OCT. Retinal vascular occlusion was mainly branched and arterial, affecting multiple vessels.<br><br>CONCLUSIONS: Although no distinct inflammatory phenotype pathognomonic to brolucizumab-related inflammation was identified, this study increases our understanding of the spectrum of posterior segment inflammatory changes that may occur in brolucizumab-treated neovascular age-related macular degeneration patients, highlighting the potential value of widefield retinal imaging and angiography to detect these inflammatory adverse events.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37869021,
year = {2024},
author = {Ahmed, Y and Reddy, M and Mederos, J and McDermott, KC and Varma, DK and Ludwig, CA and Ahmed, IK and Khaderi, KR},
title = {Democratizing Health Care in the Metaverse: How Video Games can Monitor Eye Conditions Using the Vision Performance Index: A Pilot Study.},
journal = {Ophthalmology science},
volume = {4},
number = {1},
pages = {100349},
pmid = {37869021},
issn = {2666-9145},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; },
abstract = {OBJECTIVE: In a world where digital media is deeply engrained into our everyday lives, there lies an opportunity to leverage interactions with technology for health and wellness. The Vision Performance Index (VPI) leverages natural human-technology interaction to evaluate visual function using visual, cognitive, and motor psychometric data over 5 domains: field of view, accuracy, multitracking, endurance, and detection. The purpose of this study was to describe a novel method of evaluating holistic visual function through video game-derived VPI score data in patients with specific ocular pathology.<br><br>DESIGN: Prospective comparative analysis.<br><br>PARTICIPANTS: Patients with dry eye, glaucoma, cataract, diabetic retinopathy (DR), age-related macular degeneration, and healthy individuals.<br><br>METHODS: The Vizzario Inc software development kit was integrated into 2 video game applications, Balloon Pop and Picture Perfect, which allowed for generation of VPI scores. Study participants were instructed to play rounds of each video game, from which a VPI score was compiled.<br><br>MAIN OUTCOME MEASURES: The primary outcome was VPI overall score in each comparison group. Vision Performance Index component, subcomponent scores, and psychophysical inputs were also compared.<br><br>RESULTS: Vision Performance Index scores were generated from 93 patients with macular degeneration (n&#xa0;= 10), cataract (n&#xa0;= 10), DR (n&#xa0;= 15), dry eye (n&#xa0;= 15), glaucoma (n&#xa0;= 16), and no ocular disease (n&#xa0;= 27). The VPI overall score was not significantly different across comparison groups. The VPI subcomponent "reaction accuracy" score was significantly greater in DR patients (106 &#xb1; 13.2) versus controls (96.9 &#xb1; 11.5), P&#xa0;= 0.0220. The VPI subcomponent "color detection" score was significantly lower in patients with DR (96.8 &#xb1; 2.5; p=0.0217) and glaucoma (98.5 &#xb1; 6.3; P&#xa0;= 0.0093) compared with controls (101 &#xb1; 11). Psychophysical measures were statistically significantly different from controls: proportion correct (lower in DR, age-related macular degeneration), contrast errors (higher in cataract, DR), and saturation errors (higher in dry eye).<br><br>CONCLUSIONS: Vision Performance Index scores can be generated from interactions of an ocular disease population with video games. The VPI may offer utility in monitoring select ocular diseases through evaluation of subcomponent and psychophysical input scores; however, future larger-scale studies must evaluate the validity of this tool.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37868796,
year = {2024},
author = {Kikuchi, Y and Kawczynski, MG and Anegondi, N and Neubert, A and Dai, J and Ferrara, D and Quezada-Ruiz, C},
title = {Machine Learning to Predict Faricimab Treatment Outcome in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {4},
number = {2},
pages = {100385},
pmid = {37868796},
issn = {2666-9145},
abstract = {PURPOSE: To develop machine learning (ML) models to predict, at baseline, treatment outcomes at month 9 in patients with neovascular age-related macular degeneration (nAMD) receiving faricimab.<br><br>DESIGN: Retrospective proof of concept study.<br><br>PARTICIPANTS: Patients enrolled in the phase II AVENUE trial (NCT02484690) of faricimab in nAMD.<br><br>METHODS: Baseline characteristics and spectral domain-OCT (SD-OCT) image data from 185 faricimab-treated eyes were split into 80% training and 20% test sets at the patient level. Input variables were baseline age, sex, best-corrected visual acuity (BCVA), central subfield thickness (CST), low luminance deficit, treatment arm, and SD-OCT images. A regression problem (BCVA) and a binary classification problem (reduction of CST by 35%) were considered. Overall, 10 models were developed and tested for each problem. Benchmark classical ML models (linear, random forest, extreme gradient boosting) were trained on baseline characteristics; benchmark deep neural networks (DNNs) were trained on baseline SD-OCT B-scans. Baseline characteristics and SD-OCT data were merged using 2 approaches: model stacking (using DNN prediction as an input feature for classical ML models) and model averaging (which averaged predictions from the DNN using SD-OCT volume and from classical ML models using baseline characteristics).<br><br>MAIN OUTCOME MEASURES: Treatment outcomes were defined by 2 target variables: functional (BCVA letter score) and anatomical (percent decrease in CST from baseline) outcomes at month&#xa0;9.<br><br>RESULTS: The best-performing BCVA regression model with respect to the test coefficient of determination (R[2]) was the linear model in the model-stacking approach with R[2] of 0.31. The best-performing CST classification model with respect to test area under receiver operating characteristics (AUROC) was the benchmark linear model with AUROC of 0.87. A post hoc analysis showed the baseline BCVA and the baseline CST had the most effect in the all-model prediction for BCVA regression and CST classification, respectively.<br><br>CONCLUSIONS: Promising signals for predicting treatment outcomes from baseline characteristics were detected; however, the predictive benefit of baseline images was unclear in this proof-of-concept study. Further testing and validation with larger, independent datasets is required to fully explore the predictive capacity of ML models using baseline imaging data.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37868586,
year = {2023},
author = {Kırık, F and Demirkıran, B and Ekinci Aslanoğlu, C and Koytak, A and Özdemir, H},
title = {Detection and Classification of Diabetic Macular Edema with a Desktop-Based Code-Free Machine Learning Tool.},
journal = {Turkish journal of ophthalmology},
volume = {53},
number = {5},
pages = {301-306},
pmid = {37868586},
issn = {2149-8709},
mesh = {Humans ; *Macular Edema/diagnosis ; *Diabetic Retinopathy/diagnosis ; Cross-Sectional Studies ; *Macular Degeneration ; Machine Learning ; *Diabetes Mellitus ; },
abstract = {OBJECTIVES: To evaluate the effectiveness of the Lobe application, a machine learning (ML) tool that can be used on a personal computer without requiring coding expertise, in the recognition and classification of diabetic macular edema (DME) in spectral-domain optical coherence tomography (SD-OCT) scans.<br><br>MATERIALS AND METHODS: A total of 695 cross-sectional SD-OCT images from 336 patients with DME and 200 OCT images of 200 healthy controls were included. Images with DME were classified into three main types: diffuse retinal edema (DRE), cystoid macular edema (CME), and cystoid macular degeneration (CMD). To develop the ML model, we used the desktop-based code-free Lobe application, which includes a pre-trained ResNet-50 V2 convolutional neural network and is available free of charge. The performance of the trained model in recognizing and classifying DME was evaluated with 41 DRE, 28 CMD, 70 CME, and 40 normal SD-OCT images that were not used in the training.<br><br>RESULTS: The developed model showed 99.28% sensitivity and 100% specificity for class-independent detection of DME. Sensitivity and specificity by labels were 87.80% and 98.57% for DRE, 96.43% and 99.29% for CME, and 95.71% and 95.41% for CMD, respectively.<br><br>CONCLUSION: To our knowledge, this is the first evaluation of the effectiveness of Lobe with ophthalmological images, and the results indicate that it can be used with high efficiency in the recognition and classification of DME from SD-OCT images by ophthalmologists without coding expertise.},
}
@article {pmid37867466,
year = {2023},
author = {Çeper, SB and Afrashi, F and Değirmenci, C and Menteş, J and Nalçacı, S and Akkın, C},
title = {Multimodal Imaging of Reticular Pseudodrusen in Turkish Patients.},
journal = {Turkish journal of ophthalmology},
volume = {53},
number = {5},
pages = {275-280},
pmid = {37867466},
issn = {2149-8709},
mesh = {Humans ; Ophthalmoscopy ; *Retinal Drusen/diagnosis/epidemiology ; *Macular Degeneration/diagnosis ; Fluorescein Angiography/methods ; Multimodal Imaging ; },
abstract = {OBJECTIVES: To investigate the presence and prevalence of reticular pseudodrusen (RPD) in patients with age-related macular degeneration using multiple imaging modalities and to compare the sensitivity and specificity of these modalities in the detection of RPD.<br><br>MATERIALS AND METHODS: Images from a total of 198 consecutive patients were analyzed prospectively. Color fundus photography, red-free imaging, spectral domain optical coherence tomography (SD-OCT), infrared and blue reflectance (BR) imaging, fundus autofluorescence (FAF), enhanced-depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA) and indocyanine green angiography were performed. RPD was diagnosed in the presence of relevant findings in at least two of the imaging methods used.<br><br>RESULTS: RPD were detected in 149 eyes (37.6%). In the detection of RPD, color fundus photography, red-free photography, SD-OCT, infrared, FAF, BR, and FFA imaging had sensitivity values of 50%, 57.7%, 91.6%, 95%, 74.6%, 65.7%, and 28.2% and specificity values of 99.6%, 100%, 98.4%, 94.6%, 100%, 99.6%, and 69.8%, respectively.<br><br>CONCLUSION: Infrared imaging had the highest sensitivity. SD-OCT combined with infrared imaging was the most sensitive imaging technique for detecting RPD. The high specificity of FAF, red-free, and BR imaging may be useful to confirm a diagnosis of RPD.},
}
@article {pmid37867447,
year = {2023},
author = {Coart, E and Bamps, P and Quinaux, E and Sturbois, G and Saad, ED and Burzykowski, T and Buyse, M},
title = {Minimization in randomized clinical trials.},
journal = {Statistics in medicine},
volume = {42},
number = {28},
pages = {5285-5311},
doi = {10.1002/sim.9916},
pmid = {37867447},
issn = {1097-0258},
mesh = {Humans ; Bias ; Randomized Controlled Trials as Topic ; *Research Design ; Sample Size ; },
abstract = {In randomized trials, comparability of the treatment groups is ensured through allocation of treatments using a mechanism that involves some random element, thus controlling for confounding of the treatment effect. Completely random allocation ensures comparability between the treatment groups for all known and unknown prognostic factors. For a specific trial, however, imbalances in prognostic factors among the treatment groups may occur. Although accidental bias can be avoided in the presence of such imbalances by stratifying the analysis, most trialists, regulatory agencies, and other stakeholders prefer a balanced distribution of prognostic factors across the treatment groups. Some procedures attempt to achieve balance in baseline covariates, by stratifying the allocation for these covariates, or by dynamically adapting the allocation using covariate information during the trial (covariate-adaptive procedures). In this Tutorial, the performance of minimization, a popular covariate-adaptive procedure, is compared with two other commonly used procedures, completely random allocation and stratified blocked designs. Using individual patient data of 2 clinical trials (in advanced ovarian cancer and age-related macular degeneration), the procedures are compared in terms of operating characteristics (using asymptotic and randomization tests), predictability of treatment allocation, and achieved balance. Fifty actual trials of various sizes that applied minimization for treatment allocation are used to investigate the achieved balance. Implementation issues of minimization are described. Minimization procedures are useful in all trials but especially when (1) many major prognostic factors are known, (2) many centers of different sizes accrue patients, or (3) the trial sample size is moderate.},
}
@article {pmid37867279,
year = {2024},
author = {Senrung, A and Tripathi, T and Aggarwal, N and Janjua, D and Yadav, J and Chaudhary, A and Chhokar, A and Joshi, U and Bharti, AC},
title = {Phytochemicals Showing Antiangiogenic Effect in Pre-clinical Models and their Potential as an Alternative to Existing Therapeutics.},
journal = {Current topics in medicinal chemistry},
volume = {24},
number = {4},
pages = {259-300},
pmid = {37867279},
issn = {1873-4294},
support = {5/13/4/ACB/ICRC/2020/NCD-III//Indian Council of Medical Research (ICMR-ICRC)/ ; IoE/2021/12/FRP//Institution of Eminence, University of Delhi/ ; 17-51/2016-17/CCRH/Tech/Coll./DU-Cervical Cancer.4850//CCRH/ ; 764/(CSIR-UGC NET JUNE 2019, 573(CSIR-UGC NET JUNE 2017)//University Grants Commission (UGC)/ ; 09/045(1622)/2018-EMR-I, 09/045(1629)/2019-EMR-I, 09/0045/(11635)/2021-EMR-1, 09/0045(12901)/2022-EMR-1//Council of Scientific and Industrial Research (CSIR)/ ; },
mesh = {*Angiogenesis Inhibitors/pharmacology/chemistry/chemical synthesis ; Animals ; Humans ; *Phytochemicals/pharmacology/chemistry ; Neovascularization, Pathologic/drug therapy/pathology ; },
abstract = {Angiogenesis, the formation of new blood vessels from a pre-existing vascular network, is an important hallmark of several pathological conditions, such as tumor growth and metastasis, proliferative retinopathies, including proliferative diabetic retinopathy and retinopathy of prematurity, age-related macular degeneration, rheumatoid arthritis, psoriasis, and endometriosis. Putting a halt to pathology-driven angiogenesis is considered an important therapeutic strategy to slow down or reduce the severity of pathological disorders. Considering the attrition rate of synthetic antiangiogenic compounds from the lab to reaching the market due to severe side effects, several compounds of natural origin are being explored for their antiangiogenic properties. Employing pre-clinical models for the evaluation of novel antiangiogenic compounds is a promising strategy for rapid screening of antiangiogenic compounds. These studies use a spectrum of angiogenic model systems that include HUVEC two-dimensional culture, nude mice, chick chorioallantoic membrane, transgenic zebrafish, and dorsal aorta from rats and chicks, depending upon available resources. The present article emphasizes the antiangiogenic activity of the phytochemicals shown to exhibit antiangiogenic behavior in these well-defined existing angiogenic models and highlights key molecular targets. Different models help to get a quick understanding of the efficacy and therapeutics mechanism of emerging lead molecules. The inherent variability in assays and corresponding different phytochemicals tested in each study prevent their immediate utilization in clinical studies. This review will discuss phytochemicals discovered using suitable preclinical antiangiogenic models, along with a special mention of leads that have entered clinical evaluation.},
}
@article {pmid37866681,
year = {2024},
author = {Emami-Naeini, P and Garmo, V and Boucher, N and Fernando, R and Menezes, A},
title = {Maintenance of Vision Needed to Drive after Intravitreal Anti-VEGF Therapy in Patients with Neovascular Age-related Macular Degeneration and Diabetic Macular Edema.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {4},
pages = {388-398},
doi = {10.1016/j.oret.2023.10.010},
pmid = {37866681},
issn = {2468-6530},
mesh = {Humans ; Cohort Studies ; Diabetes Mellitus ; *Diabetic Retinopathy/complications/diagnosis/drug therapy ; Intravitreal Injections ; *Macular Edema/diagnosis/drug therapy/etiology ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; },
abstract = {OBJECTIVE: To evaluate the association between intravitreal anti-VEGF therapy and visual acuity (VA)/driving vision maintenance over 4 years in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).<br><br>DESIGN: Retrospective, observational, clinical practice cohort study using data from the Vestrum Health database.<br><br>PARTICIPANTS: Initial diagnosis (January 1, 2014 to June 30, 2019) of nAMD or DME and &#x2265; 1 year of treatment/follow-up history. The VA analysis required 4 years of treatment/follow-up history. For the driving vision maintenance analysis, patients required Snellen VA of 20/40 or better at baseline and for &#x2265; 6 months during year 1 after index intravitreal anti-VEGF treatment in the better-seeing eye.<br><br>METHODS: A loss-of-driving event was the first clinic visit with VA worse than 20/40 sustained for &#x2265; 6 consecutive months. Kaplan-Meier analyses estimated the probability of maintaining driving vision over 4 years stratified by year-1 injection number. Cox proportional hazard models examined associations between baseline clinical characteristics and year-1 injection frequency and the risk of losing driving vision.<br><br>MAIN OUTCOME MEASURES: Mean change in VA over time and by baseline VA, driving vision maintenance probability over time and stratified by anti-VEGF injection frequency, and baseline factors predictive of driving vision maintenance.<br><br>RESULTS: In year 1, the nAMD and DME cohorts gained 8.5 and 9.5 ETDRS letters, respectively. Between years 1 and 4, patients with nAMD and DME lost 6.6 and 2.7 ETDRS letters, respectively. The probability of maintaining driving vision over 4 years was 56% (nAMD) and 72% (DME); among patients who received 1 to 5, 6 to 7, and &#x2265; 8 anti-VEGF injections in year 1, corresponding probabilities were 50%, 56%, and 65% (nAMD; P < 0.001) and 63%, 72%, and 77% (DME; P < 0.001). Baseline factors associated with driving vision loss included older age, worse index VA, geographic atrophy (nAMD), and worsening baseline diabetic retinopathy (DME).<br><br>CONCLUSIONS: Older age and worse index VA were risk factors for driving vision loss, whereas a greater year-1 injection number was associated with driving vision maintenance through year 4, supporting early initiation and frequent anti-VEGF injections for maintaining driving vision in nAMD or DME.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37865470,
year = {2023},
author = {Heier, JS and Lad, EM and Holz, FG and Rosenfeld, PJ and Guymer, RH and Boyer, D and Grossi, F and Baumal, CR and Korobelnik, JF and Slakter, JS and Waheed, NK and Metlapally, R and Pearce, I and Steinle, N and Francone, AA and Hu, A and Lally, DR and Deschatelets, P and Francois, C and Bliss, C and Staurenghi, G and Monés, J and Singh, RP and Ribeiro, R and Wykoff, CC and , },
title = {Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials.},
journal = {Lancet (London, England)},
volume = {402},
number = {10411},
pages = {1434-1448},
doi = {10.1016/S0140-6736(23)01520-9},
pmid = {37865470},
issn = {1474-547X},
mesh = {Humans ; Middle Aged ; Aged ; *Geographic Atrophy/drug therapy/etiology/diagnosis ; *Macular Degeneration/complications/drug therapy ; *Choroidal Neovascularization ; Double-Blind Method ; },
abstract = {BACKGROUND: Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy.<br><br>METHODS: OAKS and DERBY were two 24-month, multicentre, randomised, double-masked, sham-controlled, phase 3 studies, in which patients aged 60 years and older with geographic atrophy secondary to age-related macular degeneration were enrolled at 110 clinical sites and 122 clinical sites worldwide, respectively. Patients were randomly assigned (2:2:1:1) by central web-based randomisation system to intravitreal 15 mg per 0&#xb7;1 mL pegcetacoplan monthly or every other month, or sham monthly or every other month using stratified permuted block randomisation (stratified by geographic atrophy lesion area at screening, history or presence of active choroidal neovascularisation in the eye not under assessment, and block size of six). Study site staff, patients, reading centre personnel, evaluating physicians, and the funder were masked to group assignment. Sham groups were pooled for the analyses. The primary endpoint was the change from baseline to month 12 in the total area of geographic atrophy lesions in the study eye based on fundus autofluorescence imaging, in the modified intention-to-treat population (ie, all patients who received one or more injections of pegcetacoplan or sham and had a baseline and at least one post-baseline value of lesion area). Key secondary endpoints (measured at 24 months) were change in monocular maximum reading speed of the study eye, change from baseline in mean functional reading independence index score, change from baseline in normal luminance best-corrected visual acuity score, and change from baseline in the mean threshold sensitivity of all points in the study eye by mesopic microperimetry (OAKS only). Safety analyses included patients who were randomly assigned and received at least one injection of pegcetacoplan or sham. The now completed studies are registered with ClinicalTrials.gov, NCT03525613 (OAKS) and NCT03525600 (DERBY).<br><br>FINDINGS: Between Aug 30, 2018, and July 3, 2020, 1258 patients were enrolled in OAKS and DERBY. The modified intention-to-treat populations comprised 614 (96%) of 637 patients in OAKS (202 receiving pegcetacoplan monthly, 205 pegcetacoplan every other month, and 207 sham) and 597 (96%) of 621 patients in DERBY (201 receiving pegcetacoplan monthly, 201 pegcetacoplan every other month, and 195 sham). In OAKS, pegcetacoplan monthly and pegcetacoplan every other month significantly slowed geographic atrophy lesion growth by 21% (absolute difference in least-squares mean -0&#xb7;41 mm[2], 95% CI -0&#xb7;64 to -0&#xb7;18; p=0&#xb7;0004) and 16% (-0&#xb7;32 mm[2], -0&#xb7;54 to -0&#xb7;09; p=0&#xb7;0055), respectively, compared with sham at 12 months. In DERBY, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth, although it did not reach significance, by 12% (-0&#xb7;23 mm[2], -0&#xb7;47 to 0&#xb7;01; p=0&#xb7;062) and 11% (-0&#xb7;21 mm[2], -0&#xb7;44 to 0&#xb7;03; p=0&#xb7;085), respectively, compared with sham at 12 months. At 24 months, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth by 22% (-0&#xb7;90 mm[2], -1&#xb7;30 to -0&#xb7;50; p<0&#xb7;0001) and 18% (-0&#xb7;74 mm[2], -1&#xb7;13 to -0&#xb7;36; p=0&#xb7;0002) in OAKS, and by 19% (-0&#xb7;75 mm[2], -1&#xb7;15 to -0&#xb7;34; p=0&#xb7;0004) and 16% (-0&#xb7;63 mm[2], -1&#xb7;05 to -0&#xb7;22; p=0&#xb7;0030) in DERBY, respectively, compared with sham. There were no differences in key secondary visual function endpoints at 24 months. Serious ocular treatment-emergent adverse events were reported in five (2%) of 213, four (2%) of 212, and one (<1%) of 211 patients in OAKS, and in four (2%) of 206, two (1%) of 208, and two (1%) of 206 patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. New-onset exudative age-related macular degeneration was reported in 24 (11%), 16 (8%), and four (2%) patients in OAKS, and in 27 (13%), 12 (6%), and nine (4%) patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months.<br><br>INTERPRETATION: Pegcetacoplan, the first treatment approved by the US Food and Drug Administration for geographic atrophy, slowed geographic atrophy lesion growth with an acceptable safety profile.<br><br>FUNDING: Apellis Pharmaceuticals.},
}
@article {pmid37865012,
year = {2023},
author = {Vergroesen, JE and Thee, EF and de Crom, TOE and Kiefte-de Jong, JC and Meester-Smoor, MA and Voortman, T and Klaver, CCW and Ramdas, WD},
title = {The inflammatory potential of diet is associated with the risk of age-related eye diseases.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {42},
number = {12},
pages = {2404-2413},
doi = {10.1016/j.clnu.2023.10.008},
pmid = {37865012},
issn = {1532-1983},
mesh = {Humans ; Prospective Studies ; *Glaucoma, Open-Angle ; Diet/adverse effects ; *Cataract/epidemiology ; Inflammation/epidemiology ; *Macular Degeneration/epidemiology ; Biomarkers ; Risk Factors ; Incidence ; },
abstract = {BACKGROUND &amp; AIMS: Inflammation is involved in the pathogenesis of cataract, age-related macular degeneration (AMD), and possibly open-angle glaucoma (OAG). We assessed whether the inflammatory potential of diet (quantified using the dietary inflammatory index; DII) affects the incidence of these common blinding age-related eye diseases. Serum inflammation markers were investigated as possible mediators.<br><br>METHODS: Participants aged >45 years were selected from the prospective, population-based Rotterdam Study. From 1991 onwards, every 4-5 years, participants underwent extensive eye examinations. At baseline, blood samples and dietary data (using food frequency questionnaires) were collected. The DII was adapted based on the data available. Of the 7436 participants free of eye diseases at baseline, 4036 developed incident eye diseases during follow-up (cataract&#xa0;=&#xa0;2895, early-intermediate AMD&#xa0;=&#xa0;891, late AMD&#xa0;=&#xa0;81, OAG&#xa0;=&#xa0;169).<br><br>RESULTS: The adapted DII (aDII) ranged from&#xa0;-4.26 (i.e., anti-inflammatory) to 4.53 (i.e., pro-inflammatory). A higher aDII was significantly associated with increased inflammation. A higher neutrophil-lymphocyte ratio (NLR) was associated with an increased risk of cataract and AMD. Additionally, complement component 3c (C3c) and systemic immune-inflammation index (SII) were associated with increased risks of cataract and late AMD, respectively. Every point increase in the aDII was associated with a 9% increased risk of cataract (Odds ratio [95% confidence interval]: 1.09 [1.04-1.14]). The NLR and C3c partly mediated this association. We also identified associations of the aDII with risk of AMD (early-intermediate AMD, OR [95% CI]: 1.11 [1.03-1.19]; late AMD, OR [95% CI]: 1.24 [1.02-1.53]). The NLR partly mediated these associations. The aDII was not associated with OAG.<br><br>CONCLUSIONS: A pro-inflammatory diet was associated with increased risks of cataract and AMD. Particularly the NLR, a marker of subclinical inflammation, appears to be implicated. These findings are relevant for patients with AMD and substantiate the current recommendations to strive for a healthy lifestyle to prevent blindness.},
}
@article {pmid37864635,
year = {2024},
author = {Abdin, AD and Hanifa, O and Aljundi, W and Munteanu, C and Seitz, B and Suffo, S},
title = {Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up).},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {2},
pages = {457-468},
pmid = {37864635},
issn = {1435-702X},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; *Geographic Atrophy ; Retrospective Studies ; *Choroidal Neovascularization/diagnosis/drug therapy ; Intravitreal Injections ; Vascular Endothelial Growth Factors ; Choroid ; Tomography, Optical Coherence ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To evaluate the long-term choroidal thickness changes in combination with other morphological and functional outcomes during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD) based on the subtype of macular neovascularization (MNV): MNV-1 (within the subretinal pigment epithelium space) and MNV-2 (within the subretinal space).<br><br>METHODS: This retrospective study included 58 eyes from 53 patients with na&#xef;ve nAMD who received anti-VEGF therapy over a 60-month period. All eyes were treated initially with intravitreal bevacizumab following Pro re nata regimen. Main outcome measures included the following: subfoveal choroidal thickness (SFCT), best corrected visual acuity (BCVA), central macular thickness (CMT), development of subfoveal geographic atrophy (GA), and the number of injections.<br><br>RESULTS: Thirty-four eyes had MNV-1 (group 1) and 24 eyes had MNV-2 (group 2). SFCT in group 1 vs group 2 was (210&#x2009;&#xb1;&#x2009;45&#xa0;&#xb5;m vs 191&#x2009;&#xb1;&#x2009;52&#xa0;&#xb5;m, p&#x2009;=&#x2009;0.01) before treatment and (170&#x2009;&#xb1;&#x2009;47&#xa0;&#xb5;m vs 179&#x2009;&#xb1;&#x2009;48&#xa0;&#xb5;m, p&#x2009;=&#x2009;0.24) after 60&#xa0;months. BCVA (log MAR) in group 1 vs group 2 was (0.57&#x2009;&#xb1;&#x2009;0.18 vs 0.53&#x2009;&#xb1;&#x2009;0.22, p&#x2009;=&#x2009;0.47) before treatment and (0.59&#x2009;&#xb1;&#x2009;0.23 vs 0.69&#x2009;&#xb1;&#x2009;0.16, p&#x2009;=&#x2009;0.04) after 60&#xa0;months. CMT in group 1 vs group 2 was (398&#x2009;&#xb1;&#x2009;154&#xa0;&#xb5;m vs 382&#x2009;&#xb1;&#x2009;103&#xa0;&#xb5;m, p&#x2009;=&#x2009;0.86) before treatment and (297&#x2009;&#xb1;&#x2009;68&#xa0;&#xb5;m vs 283&#x2009;&#xb1;&#x2009;67&#xa0;&#xb5;m, p&#x2009;=&#x2009;0.14) after 60&#xa0;months. The number of injections per eye over a period of 60&#xa0;months was significantly higher in group 1 (34.9&#x2009;&#xb1;&#x2009;11 vs 29.0&#x2009;&#xb1;&#x2009;14, p&#x2009;=&#x2009;0.04). The proportion of eyes with subfoveal GA after 60&#xa0;months was significantly higher in group 2 (13 eyes, 54%) than in group 1 (9 eyes, 25%) (p&#x2009;=&#x2009;0.03).<br><br>CONCLUSION: Over the full 60&#xa0;months of anti-VEGF treatment, eyes with MNV-1 showed a greater reduction in choroidal thickness, better visual acuity, and less development of subfoveal geographic atrophy compared with eyes with MNV-2. The significantly thicker choroid in eyes with MNV type 1 at baseline seems to have a positive impact on long-term outcomes.},
}
@article {pmid37864169,
year = {2023},
author = {Sekar, R and Wooff, Y and Cioanca, AV and Kurera, M and Ngo, C and Man, SM and Natoli, R},
title = {Impairing Gasdermin D-mediated pyroptosis is protective against retinal degeneration.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
pages = {239},
pmid = {37864169},
issn = {1742-2094},
mesh = {Animals ; Mice ; Cytokines/metabolism ; Gasdermins ; Inflammasomes/metabolism ; Inflammation ; Interleukin-1beta/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; *Pyroptosis/physiology ; *Retinal Degeneration ; },
abstract = {BACKGROUND: Inflammasome activation and the subsequent release of pro-inflammatory cytokines including Interleukin 1β (IL-1β) have been widely reported to contribute to the progression of retinal degenerations, including age-related macular degeneration (AMD), the leading cause of blindness in the Western World. The role of Gasdermin D (GSDMD), a key executioner of pyroptosis following inflammasome activation, however, is less well-established. In this study we aimed to characterise the role of GSDMD in the healthy and degenerating retina, and uncover its role as a conduit for IL-1β release, including via extracellular vesicle (EV)-mediated release.<br><br>METHODS: GSDMD mutant and knockout mice, in vitro models of inflammation and a well-established in vivo model of retinal degeneration (photo-oxidative damage; PD) were utilised to explore the role and pathological contribution of GSDMD in regulating IL-1&#x3b2; release and propagating retinal inflammation. RNA sequencing of whole retinas was used to investigate GSDMD-mediated inflammation during degeneration. The role of EVs in GSDMD-mediated IL-1&#x3b2; release was investigated using nanoparticle tracking analysis, ELISA and EV inhibition paradigms. Finally, the therapeutic efficacy of targeting GSDMD was examined using GSDMD-specific siRNA.<br><br>RESULTS: We identified in this work that mice deficient in GSDMD had better-preserved retinal function, increased photoreceptor survivability and reduced inflammation. RNA-Seq analysis revealed that GSDMD may propagate inflammation in the retina via NF-&#x3ba;B signalling cascades and release of pro-inflammatory cytokines. We also showed that IL-1&#x3b2; was packaged and released via EV in a GSDMD-dependent manner. Finally, we demonstrated that impairing GSDMD function using RNAi or blocking EV release was able to reduce IL-1&#x3b2; content in cell-free supernatant and EV.<br><br>CONCLUSIONS: Taken together, these results suggest that pyroptotic pore-forming protein GSDMD plays a key role in the propagation of retinal inflammation, in particular via the release of EV-encapsulated IL-1&#x3b2;. Targeting GSDMD using genetic or pharmacological inhibitors may pose a therapeutic opportunity to dampen inflammatory cascades and delay the progression of retinal degeneration.},
}
@article {pmid37863867,
year = {2023},
author = {Ma, H and Wei, H and Zou, C and Zhu, G and Gao, Q and Zhang, N and Wang, B},
title = {Anti-VEGF Drugs in Age-Related Macular Degeneration: A Focus on Dosing Regimen-Related Safety and Efficacy.},
journal = {Drugs &amp; aging},
volume = {40},
number = {11},
pages = {991-1007},
pmid = {37863867},
issn = {1179-1969},
mesh = {Humans ; Angiogenesis Inhibitors/adverse effects ; Vascular Endothelial Growth Factor A/therapeutic use ; Pharmaceutical Preparations ; *Choroidal Neovascularization/drug therapy ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Intravitreal Injections ; Ranibizumab/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is one of the main causes of visual impairment and severe visual loss, and can progress to two advanced forms-neovascularization and atrophic. The field of anti-AMD drugs has undergone huge developments in recent years, from single-target intravitreal administration to current clinical studies with multi-target and non-invasive agents, offering interesting new pharmacological opportunities for the treatment of this disease. Hence, we summarize some of the approved anti-vascular endothelial growth factor (VEGF) drugs for neovascular AMD, especially their structural characteristics, clinical manifestations, dosing regimens, and safety issues of the anti-VEGF drugs highlighted. In addition, advances in atrophic AMD drug research are also briefly described.},
}
@article {pmid37862026,
year = {2023},
author = {García-Quintanilla, L and Almuiña-Varela, P and Maroñas, O and Gil-Rodriguez, A and Rodríguez-Cid, MJ and Gil-Martinez, M and Abraldes, MJ and Gómez-Ulla de Irazazabal, F and González-Barcia, M and Mondelo-Garcia, C and Cruz, R and Estany-Gestal, A and Fernández-Rodríguez, M and Fernández-Ferreiro, A},
title = {Influence of Genetic Polymorphisms on the Short-Term Response to Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {13},
pages = {34},
pmid = {37862026},
issn = {1552-5783},
mesh = {Humans ; *Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Cytochrome P-450 CYP2J2 ; Vascular Endothelial Growth Factor A/genetics ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy/genetics ; Polymorphism, Single Nucleotide ; Apolipoproteins E ; Intravitreal Injections ; Tomography, Optical Coherence ; Treatment Outcome ; },
abstract = {PURPOSE: To determine whether genetic risk single nucleotide polymorphisms (SNPs) for age-related macular degeneration (AMD) influence short-term response to intravitreal ranibizumab treatment.<br><br>METHODS: Forty-four treatment-naive AMD patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD. After an initial clinical examination (baseline measurement), a follow-up visit was performed to determine treatment response one month after the third injection (treatment evaluation). Patients were evaluated based on ophthalmoscopy, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Peripheral venous blood was collected for DNA analysis at baseline visit. Patients were genotyped for single-nucleotide polymorphisms within AMD-relevant genes and classified on good or poor responders based on visual acuity, central retinal thickness, intraretinal fluid, and subretinal fluid.<br><br>RESULTS: One hundred ten AMD-associated SNPs have been analyzed. Six were found to be relevant when associated to ranibizumab treatment response. The genetic variants rs890293 (CYP2J2), rs11200638 (HTRA1), rs405509 (APOE), rs9513070 (FLT1), and rs8135665 (SLC16A8) predisposed patients to a good response, whereas rs3093077 (CRP) was associated with a poor response. FTL1, SLC16A8, and APOE were the SNPs that showed significance (P < 0.05) but did not pass Bonferroni correction.<br><br>CONCLUSIONS: This is the first study that links novel polymorphisms in genes such as CRP, SCL16A8, or CYP2J2 to treatment response to ranibizumab therapy. On the other hand, HTRA1, FLT1, and APOE are linked to a good ranibizumab response. These SNPs may be good candidates for short-term treatment response biomarkers in AMD patients. However, further studies will be necessary to confirm our findings.},
}
@article {pmid37861941,
year = {2023},
author = {Hikichi, T},
title = {Investigation of satisfaction with short-term outcomes after switching to faricimab to treat neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {6},
pages = {652-656},
pmid = {37861941},
issn = {1613-2246},
mesh = {Humans ; Ranibizumab ; Angiogenesis Inhibitors ; Treatment Outcome ; Follow-Up Studies ; Receptors, Vascular Endothelial Growth Factor ; Tomography, Optical Coherence ; Intravitreal Injections ; *Retinal Diseases/drug therapy ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To investigate the outcomes and patient satisfaction at 6-months' follow-up after switching to faricimab to treat neovascular age-related macular degeneration (nAMD) with a treat-and-extend (TAE) regimen.<br><br>STUDY DESIGN: Retrospective observational study.<br><br>METHODS: Forty-eight consecutive eyes (48 patients) were switched to faricimab to treat nAMD and followed for 6 months on a TAE regimen. The Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) was administered to patients 6 months after the switch.<br><br>RESULTS: Best-corrected visual acuity (BCVA) was maintained 6 months after the switch, while the mean (&#xb1; standard error) central foveal thickness 6 months after the switch (272 &#xb1; 14 &#x3bc;m) decreased significantly compared to the time of the switch (372 &#xb1; 20 &#x3bc;m) (p < 0.001). The interval between injections 6 months after the switch was 10.45 &#xb1; 0.44 weeks, a significant extension from 6.72 &#xb1; 0.34 weeks at the switch (p = 0.002). The MacTSQ total score (58.8 &#xb1; 1.7) in eyes with a BCVA of 20/40 and better 6 months after the switch was significantly higher compared to that in eyes with a BCVA worse than 20/40 (48.2 &#xb1; 1.5) (p < 0.001). The MacTSQ total score (56.8 &#xb1; 1.8) in eyes in which a 4&#xa0;weeks extension of the injection interval was achieved was significantly higher than (49.5 &#xb1; 1.9) in eyes without (p < 0.001).<br><br>CONCLUSION: Switching to faricimab with a TAE regimen seems to maintain the BCVA and extend the injection interval in patients with nAMD, resulting in enhanced satisfaction.},
}
@article {pmid37859808,
year = {2023},
author = {Paterson, C and Cannon, J and Vargis, E},
title = {The impact of early RPE cell junction loss on VEGF, Ang-2, and TIMP secretion in vitro.},
journal = {Molecular vision},
volume = {29},
number = {},
pages = {87-101},
pmid = {37859808},
issn = {1090-0535},
support = {R15 EY028732/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Swine ; *Vascular Endothelial Growth Factor A/metabolism ; Tissue Inhibitor of Metalloproteinase-2/metabolism ; Tissue Inhibitor of Metalloproteinase-1/metabolism ; Angiopoietin-2/metabolism ; Angiogenesis Inducing Agents/metabolism ; *Macular Degeneration/pathology ; Tight Junctions/metabolism ; Retinal Pigment Epithelium/metabolism ; },
abstract = {PURPOSE: The retinal pigment epithelium (RPE) is an important tissue for maintaining a healthy retina. Retinal pigment epithelial cells help regulate nutrient transport to photoreceptors and are heavily pigmented to prevent light scattering. These cells also have junction proteins to form monolayers. Monolayers are key players in pathologies such as age-related macular degeneration (AMD), a leading cause of vision loss in older adults. During AMD, RPE cell detachment can occur, resulting in a loss of junctions. Losing junctions can increase the expression of pro-angiogenic vascular endothelial growth factor (VEGF). This overexpression can cause abnormal blood vessel growth or angiogenesis in the retina. Age-related macular degeneration treatments target VEGF to slow angiogenesis progression. However, other proteins, such as angiopoietin-2 (Ang-2) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), may also play important roles, making them potential targets for treatment. Controlling RPE junction formation will help elucidate the relationship between RPE cell detachment and additional angiogenic factor secretion, lead to more therapeutics, and increase the efficacy of current treatments.<br><br>METHODS: Micropatterning was used to control the spatial arrangement of primary porcine RPE cells using polydimethylsiloxane (PDMS) stencils. Patterns were formed into PDMS stencils to mimic 10%, 25%, and 50% overall detachment of the RPE monolayer. Zonula-occludens-1 (ZO-1), Ang-2, and VEGF were visualized using immunocytochemical (ICC) staining. An enzyme-linked immunosorbent assay (ELISA) was used to quantify extracellular Ang-2, VEGF, TIMP-1, and TIMP-2 levels. A rod outer segment (OS) phagocytosis assay was performed to determine how RPE junction loss directly affects photoreceptor support.<br><br>RESULTS: The growth of primary porcine RPE cells was successfully controlled using stencils. Morphological changes and a decrease in pigmentation were observed, showing a decline in barrier and light absorption functions as degeneration increased. One day after stencil removal, junction proteins were delocalized, and angiogenic factor secretions were correlated with increased levels of detachment. Secretion levels of Ang-2 and TIMP-1 were significantly increased, whereas VEGF and TIMP-2 concentrations were not as affected by varying levels of detachment. OS phagocytosis appeared lower in RPE cells when ZO-1 was affected.<br><br>CONCLUSIONS: These results suggest a correlation between loss of junctions, abnormal angiogenic protein secretion, and reduced OS phagocytosis. Furthermore, Ang-2 and TIMP-1 proteins might be beneficial targets for AMD treatments, and their roles in retinal diseases deserve further investigation.},
}
@article {pmid37859807,
year = {2023},
author = {Chen, Y and Zhou, Y and Zhu, X and Yan, G and Pan, D and Wang, L and Yang, M and Wang, K},
title = {PET imaging of retinal inflammation in mice exposed to blue light using [[18]F]-DPA-714.},
journal = {Molecular vision},
volume = {29},
number = {},
pages = {117-124},
pmid = {37859807},
issn = {1090-0535},
mesh = {Mice ; Animals ; Tissue Distribution ; *Fluorine Radioisotopes ; Mice, Inbred C57BL ; *Inflammation/diagnostic imaging ; Positron-Emission Tomography/methods ; Retina/diagnostic imaging ; Carrier Proteins ; },
abstract = {PURPOSE: Positron emission tomography (PET) is widely used in high-precision imaging, which may provide a simple and noninvasive method for the detection of pathology and therapeutic effects. [[18]F]-DPA-714 is a second-generation translocator protein (TSPO) positron emission tomography radiotracer that shows great promise in a model of neuroinflammation. In this study, [[18]F]-DPA-714 micro-PET imaging was used to evaluate retinal inflammation in mice exposed to blue light, a well-established model of age-related macular degeneration (AMD) for molecular mechanism research and drug screening.<br><br>METHODS: C57BL/6J melanized mice were subjected to 10,000, 15,000, and 20,000&#xa0;lux blue light for 5 days (8 h/day) to develop the retinal injury model, and the structure and function of the retina were assessed using hematoxylin-eosin (HE) staining, electroretinography (ERG), and terminal-deoxynucleotidyl transferase (TdT)-mediated nick-end labeling (TUNEL) immunostaining. Then, [[18]F]-DPA-714 was injected approximately 100 &#x3bc;Ci through each tail vein, and static imaging was performed 1 h after injection. Finally, the mice eyeballs were collected for biodistribution and immune analysis.<br><br>RESULTS: The blue light exposure significantly destroyed the structure and function of the retina, and the uptake of [[18]F]-DPA-714 in the retinas of the mice exposed to blue light were the most significantly upregulated, which was consistent with the biodistribution data. In addition, the immunohistochemical, western blot, and immunofluorescence data showed an increase in microglial TSPO expression.<br><br>CONCLUSIONS: [[18]F]-DPA-714 micro-PET imaging might be a good method for evaluating early inflammatory status during retinal pathology.},
}
@article {pmid37858911,
year = {2023},
author = {Hurley, DJ and Gallagher, D and Petronzi, V and O'Rourke, M and Kinsella, F and Townley, D},
title = {Examining the efficacy of verteporfin photo-dynamic therapy (PDT) at different dose &amp; fluence levels.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {44},
number = {},
pages = {103848},
doi = {10.1016/j.pdpdt.2023.103848},
pmid = {37858911},
issn = {1873-1597},
mesh = {Humans ; Verteporfin/therapeutic use ; Photosensitizing Agents ; *Photochemotherapy/methods ; Retrospective Studies ; *Porphyrins ; Treatment Outcome ; *Macular Degeneration/drug therapy ; *Central Serous Chorioretinopathy/drug therapy ; *Hemangioma/drug therapy ; *Telangiectasis/chemically induced/complications/drug therapy ; Tomography, Optical Coherence ; },
abstract = {OBJECTIVES: Photodynamic therapy (PDT) is a vaso-occlusive treatment for a number of chorioretinal vascular pathologies. We aimed to retrospectively analyse efficiency and safety of PDT for different conditions (central serous retinopathy (CSR), age-related macular degeneration (AMD), macular telangiectasia type 2 and choroidal hemangioma) and with different verteporfin parameters.<br><br>METHODS: Clinical parameters were ascertained from the medical records of patients undergoing PDT over a 6-year period. This included indications for PDT, dosing regimens of verteporfin PDT (which includes treatment dose of verteporfin and fluence). Response to treatment was measured by best corrected visual acuity (BCVA) and central foveal thickness (CFT) on ocular coherence tomography. Complications and side effects were recorded.<br><br>RESULTS: 67.4&#xa0;% (31/46) of PDT treatments performed over the last six years were for CSR. In the CSR cohort, there were significant improvements in BCVA (0.47&#xa0;&#xb1;&#xa0;0.24 to 0.29&#xa0;&#xb1;&#xa0;0.27, p&#xa0;<&#xa0;0.05) and CFT (350.2&#x3bc;m&#xa0;&#xb1;&#xa0;66.9&#xa0;&#x3bc;m to 286.1&#x3bc;m&#xa0;&#xb1;&#xa0;60.6&#xa0;&#x3bc;m. In the AMD cohort, there was no change in BCVA (1.08&#xa0;&#xb1;&#xa0;0.52 to 1.07&#xa0;&#xb1;&#xa0;0.53, p&#xa0;=&#xa0;0.96) but significant improvement in CFT (488.2&#x3bc;m&#xa0;&#xb1;&#xa0;164.6&#xa0;&#x3bc;m to 348.7&#x3bc;m&#xa0;&#xb1;&#xa0;65.7&#xa0;&#x3bc;m, p&#xa0;<&#xa0;0.05). There was no significant difference in BCVA or CFT for macular telangiectasia type 2 and choroidal hemangioma.<br><br>CONCLUSIONS: PDT continues to have a role in the management of medical retina conditions. Our results show PDT is most effective in improving and stabilizing visual acuity in CSR, with earlier intervention resulting in better outcomes.},
}
@article {pmid37858375,
year = {2024},
author = {Yang, TM and Huang, WL and Yang, CH and Yang, CM and Ho, TC and Chen, TC and Lai, TT and Hsieh, YT},
title = {Association between non-steroidal anti-inflammatory drug use and development of age-related macular degeneration-A 10-year retrospective cohort study.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {123},
number = {4},
pages = {467-477},
doi = {10.1016/j.jfma.2023.09.014},
pmid = {37858375},
issn = {0929-6646},
mesh = {Humans ; Retrospective Studies ; Angiogenesis Inhibitors ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/chemically induced/drug therapy ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Aspirin/therapeutic use ; *Cardiovascular Diseases ; *Arthritis/chemically induced/drug therapy ; Risk Factors ; },
abstract = {PURPOSE: To analyze the associations between development of age-related macular degeneration (AMD) and regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs).<br><br>METHODS: We retrospectively recruited individuals who received &#x2265;28-day prescriptions of aspirin or NA-NSAIDs exclusively between 2008 and 2017 in one tertiary center as regular users. Non-regular users were free from regular use of any anti-inflammatory drugs and were matched to regular users in terms of age, sex, and visit date at a ratio of 1-4:1. The aspirin cohort included 36,771 regular users and 110,808 matched non-regular users, while the NA-NSAID cohort included 59,569 regular users and 179,732 matched non-regular users. Stratified multivariate Cox regression analyses with adjustment for systemic confounding factors were performed for the development of AMD and neovascular AMD.<br><br>RESULTS: In the aspirin cohort, the adjusted hazard ratios of aspirin use for AMD in the whole cohort, individuals without cardiovascular diseases (CVDs), and those with CVDs were 0.664, 0.618, and 0.702, respectively (P&#xa0;<&#xa0;0.0001 for all), while those of aspirin use for neovascular AMD were 0.486, 0.313, and 0.584 (P&#xa0;<&#xa0;0.05 for all), respectively. In the NA-NSAID cohort, regular use of NA-NSAIDs was associated with a decreased risk of AMD (hazard ratio&#xa0;=&#xa0;0.823, P&#xa0;<&#xa0;0.0001) and neovascular AMD (hazard ratio&#xa0;=&#xa0;0.720, P&#xa0;=&#xa0;0.040) only in people without arthritis.<br><br>CONCLUSIONS: Regular use of aspirin or NA-NSAIDs had protective effects on AMD and neovascular AMD. The effect of aspirin was observed in all patients, while the effect of NA-NSAIDs was observed only in people without arthritis.},
}
@article {pmid37858232,
year = {2023},
author = {Droho, S and Voigt, AP and Sterling, JK and Rajesh, A and Chan, KS and Cuda, CM and Perlman, H and Lavine, JA},
title = {NR4A1 deletion promotes pro-angiogenic polarization of macrophages derived from classical monocytes in a mouse model of neovascular age-related macular degeneration.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
pages = {238},
pmid = {37858232},
issn = {1742-2094},
support = {R01 EY034486/EY/NEI NIH HHS/United States ; P01 AG049665/AG/NIA NIH HHS/United States ; R01 AI170938/AI/NIAID NIH HHS/United States ; AG049665/AG/NIA NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; K08 EY030923/EY/NEI NIH HHS/United States ; EY030923/EY/NEI NIH HHS/United States ; CA060553/CA/NCI NIH HHS/United States ; AR075423/AR/NIAMS NIH HHS/United States ; R01 AR075423/AR/NIAMS NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Choroidal Neovascularization/genetics ; Disease Models, Animal ; Macrophages/physiology ; *Macular Degeneration/genetics ; Mice, Inbred C57BL ; Microglia ; Monocytes ; },
abstract = {BACKGROUND: Neovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1[-/-] mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. NR4A1 is a transcription factor that is necessary for maturation of non-classical monocytes from classical monocytes. While Nr4a1[-/-] mice are deficient in non-classical monocytes, results are confounded by macrophage hyper-activation. Nr4a1[se2/se2] mice lack a transcriptional activator, resulting in non-classical monocyte loss without macrophage hyper-activation.<br><br>MAIN BODY: We subjected Nr4a1[-/-] and Nr4a1[se2/se2] mice to the laser-induced CNV model and performed multi-parameter flow cytometry. We found that both models lack non-classical monocytes, but only Nr4a1[-/-] mice displayed increased CNV area. Additionally, CD11c[+] macrophages were increased in Nr4a1[-/-] mice. Single-cell transcriptomic analysis uncovered that CD11c[+] macrophages were enriched from Nr4a1[-/-] mice and expressed a pro-angiogenic transcriptomic profile that was disparate from prior reports of macrophage hyper-activation.<br><br>CONCLUSIONS: These results suggest that non-classical monocytes are dispensable during CNV, and NR4A1 deficiency results in increased recruitment of pro-angiogenic macrophages.},
}
@article {pmid37857454,
year = {2024},
author = {Vingopoulos, F and Bannerman, A and Zhou, P and Koch, T and Wescott, HE and Kim, L and Vavvas, D and Miller, JW and Miller, JB},
title = {Towards the validation of quantitative contrast sensitivity as a clinical endpoint: correlations with vision-related quality of life in bilateral AMD.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {6},
pages = {846-851},
doi = {10.1136/bjo-2023-323507},
pmid = {37857454},
issn = {1468-2079},
mesh = {Humans ; *Quality of Life ; Prospective Studies ; *Contrast Sensitivity/physiology ; Female ; Cross-Sectional Studies ; Male ; *Visual Acuity/physiology ; Aged ; Surveys and Questionnaires ; Aged, 80 and over ; Sickness Impact Profile ; Macular Degeneration/physiopathology/psychology ; Middle Aged ; },
abstract = {AIM: To investigate if active learning of contrast sensitivity (CS) in bilateral age-related macular degeneration (AMD) correlates better than visual acuity (VA) with vision-related quality of life (VRQoL) using factor analysis-calibrated National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25).<br><br>METHODS: Prospective cross-sectional observational study in 93 patients (186 eyes) with bilateral AMD. CS was measured in one eye at a time with the quantitative CS function (qCSF) method (Adaptive Sensory Technology). Same-day VRQoL was assessed with factor analysis-calibrated NEI VFQ-25 visual function and socioemotional scales. Mixed-effects multiple linear regression analyses evaluated the associations of the qCSF outcomes and VA with the NEI VFQ-25 scales. A subgroup analysis on patients with AMD with VA more than 20/25 in both eyes was performed.<br><br>RESULTS: Compared with VA, CS outcomes were associated with larger effect on both visual function scale (standardised beta coefficients (&#x3b2;*) for area under the logarithm of CSF (AULCSF) curve and CS thresholds at 1.5, 3 and 6 cycles per degree (cpd): &#x3b2;*=0.50, 0.48, 0.52, 0.46, all p<0.001, respectively, vs &#x3b2;*=-0.45 for VA, all p<0.001) and socioemotional scale (&#x3b2;* for AULCSF and CS threshold at 6 cpd: &#x3b2;*=0.44, 0.44 vs &#x3b2;*=-0.42 for VA, all p<0.001). In patients with AMD with VA more than 20/25 in both eyes (N=20), both VFQ-25 scales and all CS outcomes were significantly reduced.<br><br>CONCLUSIONS: qCSF-measured CS strongly correlates with patient-reported VRQoL in bilateral AMD, even stronger than VA does. This study further validates qCSF-measured CS as a promising functional endpoint for future clinical trials in AMD.},
}
@article {pmid37856460,
year = {2023},
author = {Budnik, A and Palewski, M and Michnowska-Kobylińska, M and Lisowski, &#x141; and Łapińska, M and Stachurska, Z and Szpakowicz, A and Konstantynowicz, J and Kamiński, K and Konopińska, J},
title = {The prevalence of age-related macular degeneration and osteoporosis in the older Polish population: Is there a link?.},
journal = {PloS one},
volume = {18},
number = {10},
pages = {e0293143},
pmid = {37856460},
issn = {1932-6203},
mesh = {Female ; Humans ; Male ; Bone Density ; *Macular Degeneration/epidemiology ; *Osteoporosis/epidemiology ; Poland/epidemiology ; Prevalence ; Quality of Life ; Middle Aged ; Aged ; Aged, 80 and over ; },
abstract = {BACKGROUND: Age-related macular degeneration is the primary cause of irreversible blindness in developed countries, whereas the global prevalence of osteoporosis-a major public health problem-is 19.7%. Both diseases may coincide in populations aged >50 years, leading to serious health deterioration and decreased quality of life.<br><br>OBJECTIVES: This study aimed to analyze the relationship between age-related macular degeneration and osteopenia, defined as decreased bone mineral density, in the Polish population.<br><br>METHODS: Participants were derived from the population-based Bialystok PLUS Study. Randomized individuals were stratified into two groups, those with age-related macular degeneration (AMD-1 group) or without age-related macular degeneration (AMD-0 group). Using a cutoff value of -1.0 to identify low bone mass, participants with femoral bone mineral density T-scores above -1.0 were assigned to the normal reference, and those with T-scores below -1.0 were assigned to the osteopenia category. Among 436 Caucasian participants aged 50-80 years (252 women, 184 men), the prevalence of age-related macular degeneration was 9.9% in women and 12.0% in men. Decreased bone mineral density based on T-scores was observed in 36.9% of women and in 18.9% of men. Significant differences in femoral bone mineral density between the AMD-0 and AMD-1 groups were detected only in men (mean difference [95% confidence interval] = 0.11 (0.02; 0.13); p = 0.012 for femoral bone mineral density, and 0.73 [0.015; 0.94]; p = 0.011 for the femoral T-score). No associations were observed between bone mineral density and age-related macular degeneration in women.<br><br>CONCLUSION: Decreased femoral bone mineral density may be associated with a higher risk of age-related macular degeneration in men, but a causal link remains unclear.},
}
@article {pmid37856139,
year = {2023},
author = {Dow, ER and Jeong, HK and Katz, EA and Toth, CA and Wang, D and Lee, T and Kuo, D and Allingham, MJ and Hadziahmetovic, M and Mettu, PS and Schuman, S and Carin, L and Keane, PA and Henao, R and Lad, EM},
title = {A Deep-Learning Algorithm to Predict Short-Term Progression to Geographic Atrophy on Spectral-Domain Optical Coherence Tomography.},
journal = {JAMA ophthalmology},
volume = {141},
number = {11},
pages = {1052-1061},
pmid = {37856139},
issn = {2168-6173},
support = {MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; K23 EY026988/EY/NEI NIH HHS/United States ; R01 EY023039/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Algorithms ; *Deep Learning ; Disease Progression ; *Geographic Atrophy/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Clinical Trials as Topic ; },
abstract = {IMPORTANCE: The identification of patients at risk of progressing from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) is essential for clinical trials aimed at preventing disease progression. DeepGAze is a fully automated and accurate convolutional neural network-based deep learning algorithm for predicting progression from iAMD to GA within 1 year from spectral-domain optical coherence tomography (SD-OCT) scans.<br><br>OBJECTIVE: To develop a deep-learning algorithm based on volumetric SD-OCT scans to predict the progression from iAMD to GA during the year following the scan.<br><br>This retrospective cohort study included participants with iAMD at baseline and who either progressed or did not progress to GA within the subsequent 13 months. Participants were included from centers in 4 US states. Data set 1 included patients from the Age-Related Eye Disease Study 2 AREDS2 (Ancillary Spectral-Domain Optical Coherence Tomography) A2A study (July 2008 to August 2015). Data sets 2 and 3 included patients with imaging taken in routine clinical care at a tertiary referral center and associated satellites between January 2013 and January 2023. The stored imaging data were retrieved for the purpose of this study from July 1, 2022, to February 1, 2023. Data were analyzed from May 2021 to July 2023.<br><br>EXPOSURE: A position-aware convolutional neural network with proactive pseudointervention was trained and cross-validated on Bioptigen SD-OCT volumes (data set 1) and validated on 2 external data sets comprising Heidelberg Spectralis SD-OCT scans (data sets 2 and 3).<br><br>MAIN OUTCOMES AND MEASURES: Prediction of progression to GA within 13 months was evaluated with area under the receiver-operator characteristic curves (AUROC) as well as area under the precision-recall curve (AUPRC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.<br><br>RESULTS: The study included a total of 417 patients: 316 in data set 1 (mean [SD] age, 74 [8]; 185 [59%] female), 53 in data set 2, (mean [SD] age, 83 [8]; 32 [60%] female), and 48 in data set 3 (mean [SD] age, 81 [8]; 32 [67%] female). The AUROC for prediction of progression from iAMD to GA within 1 year was 0.94 (95% CI, 0.92-0.95; AUPRC, 0.90 [95% CI, 0.85-0.95]; sensitivity, 0.88 [95% CI, 0.84-0.92]; specificity, 0.90 [95% CI, 0.87-0.92]) for data set 1. The addition of expert-annotated SD-OCT features to the model resulted in no improvement compared to the fully autonomous model (AUROC, 0.95; 95% CI, 0.92-0.95; P&#x2009;=&#x2009;.19). On an independent validation data set (data set 2), the model predicted progression to GA with an AUROC of 0.94 (95% CI, 0.91-0.96; AUPRC, 0.92 [0.89-0.94]; sensitivity, 0.91 [95% CI, 0.74-0.98]; specificity, 0.80 [95% CI, 0.63-0.91]). At a high-specificity operating point, simulated clinical trial recruitment was enriched for patients progressing to GA within 1 year by 8.3- to 20.7-fold (data sets 2 and 3).<br><br>CONCLUSIONS AND RELEVANCE: The fully automated, position-aware deep-learning algorithm assessed in this study successfully predicted progression from iAMD to GA over a clinically meaningful time frame. The ability to predict imminent GA progression could facilitate clinical trials aimed at preventing the condition and could guide clinical decision-making regarding screening frequency or treatment initiation.},
}
@article {pmid37855978,
year = {2023},
author = {Haritoglou, C},
title = {[Vitrectomy/vitreous body and age related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {120},
number = {10},
pages = {990-991},
pmid = {37855978},
issn = {2731-7218},
mesh = {Humans ; *Vitreous Body ; Vitrectomy/adverse effects ; *Macular Degeneration/surgery ; Vitreous Hemorrhage/surgery ; },
}
@article {pmid37854772,
year = {2023},
author = {Tao, Q and Zhang, C and Mercier, G and Lunetta, K and Ang, TFA and Akhter-Khan, S and Zhang, Z and Taylor, A and Killiany, RJ and Alosco, M and Mez, J and Au, R and Zhang, X and Farrer, LA and Qiu, WWQ and , },
title = {Identification of an APOE ε4-specific blood-based molecular pathway for Alzheimer's disease risk.},
journal = {Alzheimer's &amp; dementia (Amsterdam, Netherlands)},
volume = {15},
number = {4},
pages = {e12490},
pmid = {37854772},
issn = {2352-8729},
support = {R01 AG046171/AG/NIA NIH HHS/United States ; U01 AG024904/AG/NIA NIH HHS/United States ; R01 EY025961/EY/NEI NIH HHS/United States ; K24 AG050842/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; U19 AG068753/AG/NIA NIH HHS/United States ; },
abstract = {INTRODUCTION: The precise apolipoprotein E (APOE) ε4-specific molecular pathway(s) for Alzheimer's disease (AD) risk are unclear.<br><br>METHODS: Plasma protein modules/cascades were analyzed using weighted gene co-expression network analysis (WGCNA) in the Alzheimer's Disease Neuroimaging Initiative study. Multivariable regression analyses were used to examine the associations among protein modules, AD diagnoses, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), and brain glucose metabolism, stratified by APOE genotype.<br><br>RESULTS: The Green Module was associated with AD diagnosis in APOE &#x3b5;4 homozygotes. Three proteins from this module, C-reactive protein (CRP), complement C3, and complement factor H (CFH), had dose-dependent associations with CSF p-tau and cognitive impairment only in APOE &#x3b5;4 homozygotes. The link among these three proteins and glucose hypometabolism was observed in brain regions of the default mode network (DMN) in APOE &#x3b5;4 homozygotes. A Framingham Heart Study validation study supported the findings for AD.<br><br>DISCUSSION: The study identifies the APOE &#x3b5;4-specific CRP-C3-CFH inflammation pathway for AD, suggesting potential drug targets for the disease.Highlights: Identification of an APOE &#x3b5;4 specific molecular pathway involving blood CRP, C3, and CFH for the risk of AD.CRP, C3, and CFH had dose-dependent associations with CSF p-Tau and brain glucose hypometabolism as well as with cognitive impairment only in APOE &#x3b5;4 homozygotes.Targeting CRP, C3, and CFH may be protective and therapeutic for AD onset in APOE &#x3b5;4 carriers.},
}
@article {pmid37854550,
year = {2023},
author = {Wei, F and Hagan, K and Viehland, C and Tao, YK and Kuo, AN and Izatt, JA and Dhalla, AH},
title = {Hybrid spiral scanning in a double-clad fiber-based handheld confocal scanning light ophthalmoscope.},
journal = {Biomedical optics express},
volume = {14},
number = {10},
pages = {5162-5181},
pmid = {37854550},
issn = {2156-7085},
support = {R21 EY033515/EY/NEI NIH HHS/United States ; R01 EY030490/EY/NEI NIH HHS/United States ; R01 EY031769/EY/NEI NIH HHS/United States ; R21 EY030270/EY/NEI NIH HHS/United States ; R01 EY033969/EY/NEI NIH HHS/United States ; },
abstract = {High-speed, accessible, and robust in vivo imaging of the human retina is critical for screening of retinal pathologies, such as diabetic retinopathy, age-related macular degeneration, and others. Scanning light ophthalmoscopy (SLO) is a retinal imaging modality that produces digital, en face images of the human retina with superior image gradability rates when compared to the current standard of care in screening for these diseases, namely the flood-illumination handheld fundus camera (HFC). However, current-generation commercial SLO systems are mostly tabletop devices, limiting their accessibility and utility in screening applications. Moreover, most existing SLO systems use raster scan patterns, which are both inefficient and lead to undesired subject gaze drift when used with visible or pseudo-visible illumination. Non-raster scan patterns, especially spiral scanning as described herein, promise advantages in both scan efficiency and reduced subject eye motion. In this work, we introduce a novel "hybrid spiral" scan pattern and the associated hardware design and real-time image reconstruction techniques necessary for its implementation in an SLO system. Building upon this core hybrid spiral scanning SLO (HSS-SLO) technology, we go on to present a complete handheld HSS-SLO system, featuring a fiber-coupled portable patient interface which leverages a dual-clad fiber (DCF) to form a single-path optical topology, thus ensuring mechanically robust co-alignment of illumination and collection apertures, a necessity for a handheld system. The feasibility of HSS-SLO for handheld, in vivo imaging is demonstrated by imaging eight human volunteers.},
}
@article {pmid37854491,
year = {2023},
author = {Bahavarnia, F and Baghban, HN and Eskandani, M and Hasanzadeh, M},
title = {Microfluidic paper-based colorimetric quantification of malondialdehyde using silver nanoprism toward on-site biomedical analysis: a new platform for the chemical sensing and biosensing of oxidative stress.},
journal = {RSC advances},
volume = {13},
number = {43},
pages = {30499-30510},
pmid = {37854491},
issn = {2046-2069},
abstract = {Malondialdehyde (MDA) is a critical product of polyunsaturated adipose acid peroxidation and represents a common biomarker of oxidative stress. The effect of different MDA concentrations on human biofluids reflects pathological changes, which has been seen in diverse types of sickness, such as leukemia, diabetes, cancer, cardiovascular disease, and age-related macular degeneration and liver disease. In this study, different types of silver nanoparticles, including silver nanoprism (AgNPrs), silver nanowires (AgNWs), and silver nanospheres (AgNSs), were synthesized and used for the chemosensing of MDA by colorimetric and spectrophotometric methods. Colorimetric tests were performed to identify malondialdehyde in the solution as well as the one-droplet-based microfluidic paper substrate as a miniaturization device for the monitoring of analytes in human real samples. The analytical quantification of the MDA was done using the UV-Vis method. Also, the utilization of the designed chemosensor for the analysis of MDA in real sample was evaluated in human urine samples. Using the spectrophotometric method, MDA was deformed in the linear range of 0.01192 to 1.192 mM with a low limit of quantification of 0.12 μM. Essential significant features of this study include the first application of AgNPrs with high stability and great optical properties without any reagent as an optical sensing probe of MDA and optimized OD-μPCD toward on-site and on-demand MDA screening in real samples diagnosis and the innovative time/color semi-analytical recognition strategy. Moreover, the prepared OD-μPCD decorated by AgNPrs could be a prized candidate for commercialization due to the benefits of the low-cost materials used, like paper and paraffin, and portability. This innovative process led to uniform hydrophilic micro-channels on the surface of cellulose, without the use of a UV lamp, clean room, and organic solvents. This report could be a pioneering work, inspiring simple and effective on-site semi-analytical recognition devices for harmful substances or illegal drugs, which simply consist of a piece of lightweight paper and one drop of the required reagent.},
}
@article {pmid37853106,
year = {2024},
author = {Chandra, S and Gurudas, S and Burton, BJL and Menon, G and Pearce, I and Mckibbin, M and Kotagiri, A and Talks, J and Grabowska, A and Ghanchi, F and Gale, R and Giani, A and Chong, V and Yamaguchi, TCN and Pal, B and Thottarath, S and Pakeer, RM and Chandak, S and Montesel, A and Sivaprasad, S},
title = {Associations of presenting visual acuity with morphological changes on OCT in neovascular age-related macular degeneration: PRECISE Study Report 2.},
journal = {Eye (London, England)},
volume = {38},
number = {4},
pages = {757-765},
pmid = {37853106},
issn = {1476-5454},
mesh = {Humans ; Male ; Female ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Tomography, Optical Coherence ; Fluorescein Angiography ; Fibrosis ; *Macular Degeneration/drug therapy ; Visual Acuity ; Atrophy ; Ranibizumab ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To study associations of optical coherence tomography (OCT) features with presenting visual acuity (VA) in treatment naive neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA&#x2009;&#x2265;&#x2009;68 ETDRS letters, Snellen &#x2265; 6/12) and poor VA (VA&#x2009;<&#x2009;54 letters, Snellen&#x2009;<&#x2009;6/18) were analysed using Generalised Estimating Equations to account for inter-eye correlation.<br><br>RESULTS: Of 2274 eyes of 2128 patients enrolled, 2039 eyes of 1901 patients with complete data were analysed. Mean age was 79.4 (SD 7.8) years, female:male 3:2 and mean VA 58.0 (SD 14.5) letters. On multivariable analysis VA&#x2009;<&#x2009;54 letters was associated with increased central subfield thickness (CST) (OR 1.40 per 100&#x2009;&#xb5;m; P&#x2009;<&#x2009;0.001), foveal intraretinal fluid (OR 2.14; P&#x2009;<&#x2009;0.001), polypoidal vasculopathy (PCV) relative to Type 1 macular neovascularisation (MNV) (OR 1.66; P&#x2009;=&#x2009;0.049), presence of foveal subretinal hyperreflective material (SHRM) (OR 1.73; P&#x2009;=&#x2009;0.002), foveal fibrosis (OR 3.85; P&#x2009;<&#x2009;0.001), foveal atrophy (OR 5.54; P&#x2009;<&#x2009;0.001), loss of integrity of the foveal ellipsoid zone (EZ) or external limiting membrane (ELM) relative to their preservation (OR 3.83; P&#x2009;<&#x2009;0.001) and absence of subretinal drusenoid deposits (SDD) (presence vs absence; OR 0.75; P&#x2009;=&#x2009;0.04). These features were associated with reduced odds of VA&#x2009;&#x2265;&#x2009;68 letters except MNV subtypes and SDD.<br><br>CONCLUSION: Presence of baseline fovea-involving atrophy, fibrosis, intraretinal fluid, SHRM, PCV EZ/ELM loss and increased CST determine poor presenting VA. This highlights the need for early detection and treatment prior to structural changes that worsen baseline VA.},
}
@article {pmid37851142,
year = {2023},
author = {Gonzalez-Lopez, JJ and Arruza Santos, ME and Leon Garcia, J},
title = {Pars plana vitrectomy in patients aged 85 years and older: a single-centre, retrospective cohort study.},
journal = {International ophthalmology},
volume = {43},
number = {12},
pages = {4887-4896},
pmid = {37851142},
issn = {1573-2630},
support = {MWG#76035373//Alcon/ ; },
mesh = {Male ; Humans ; Aged, 80 and over ; Vitrectomy/methods ; Retrospective Studies ; *Retinal Detachment/surgery/etiology ; *Eye Diseases/etiology ; *Eye Injuries/etiology ; *Renal Insufficiency, Chronic/etiology/surgery ; },
abstract = {PURPOSE: To describe the epidemiology, indications and surgical results of pars plana vitrectomy (PPV) in patients over 85 years of age.<br><br>METHODS: A retrospective cohort study was performed including all consecutive patients aged 85&#xa0;years or older who underwent PPV between September 2018 and March 2022 in a single hospital in Madrid, Spain. Data on diagnosis, comorbidities, surgical indication, surgical details, surgical complications and surgical outcomes were collected from medical records.<br><br>RESULTS: A total of 124 eyes of 119 patients (56 males, 47.1%) underwent PPV. Median age was 87&#xa0;years (range 85-96). The most common surgical indications were complications of cataract surgery in 34 patients (28.6%), macular epiretinal membrane in 32 (26.9%), and rhegmatogenous retinal detachment (RRD) in 12 (10.1%). Mean preoperative best corrected visual acuity (BCVA) was 13.33&#x2009;&#xb1;&#x2009;42.34 ETDRS letters and improved to 40.05&#x2009;&#xb1;&#x2009;41.04 letters at 3&#xa0;months (p&#x2009;<&#x2009;0.001). BCVA had improved in 68.82% of patients at 3&#xa0;months. Patients with chronic kidney disease (CKD; p&#x2009;<&#x2009;0.001), RRD (p&#x2009;=&#x2009;0.003), ocular trauma (p&#x2009;=&#x2009;0.001) and age-related macular degeneration (AMD; p&#x2009;=&#x2009;0.002) showed worse BCVA at 3&#xa0;months from surgery. Patients with better preoperative BCVA (p&#x2009;<&#x2009;0.001), and those who underwent 25G PPV (p&#x2009;=&#x2009;0.041) showed better visual outcomes.<br><br>CONCLUSIONS: PPV is an effective technique for improving visual acuity in patients aged 85 years and older with vitreoretinal diseases. Visual outcomes were better when patients had a better preoperative visual acuity and underwent 25G PPV. Patients with a previous diagnosis of AMD or CKD, and those undergoing surgery for ocular trauma or RRD had worse visual outcomes.},
}
@article {pmid37850566,
year = {2024},
author = {Teng, L and Sun, Y and Teng, S and Hui, P},
title = {Applications of nanomaterials in anti-VEGF treatment for ophthalmic diseases.},
journal = {Journal of biomedical materials research. Part A},
volume = {112},
number = {2},
pages = {296-306},
doi = {10.1002/jbm.a.37626},
pmid = {37850566},
issn = {1552-4965},
support = {20200201424JC//Natural Science Foundation of Jilin Province/ ; },
mesh = {Humans ; Infant, Newborn ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; *Choroidal Neovascularization/drug therapy ; *Diabetic Retinopathy/chemically induced/drug therapy ; Injections ; *Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {Angiogenesis has been determined to be essential in the occurrence and metastasis of diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), choroidal neovascularization (CNV), retinopathy of prematurity (ROP), tumor, etc. However, the clinical use of anti-vascular endothelial growth factors (VEGF) drugs is currently limited due to its high cost, potential side effects, and need for repeated injections. In recent years, nanotechnology has shown promising results in inhibiting neovascularization and reducing reactive oxygen species (ROS) or inflammatory factors. Some nanomaterials can also act as vehicles for drug delivery, such as lipid nanoparticles and PLGA. The process of angiogenesis and its molecular mechanism are discussed in this article. At the same time, this study aims to systematically review the research progress of nanotechnology and offer more treatment options for neovascularization-related diseases in clinical ophthalmology.},
}
@article {pmid37848361,
year = {2023},
author = {Boya, P and Kaarniranta, K and Handa, JT and Sinha, D},
title = {Lysosomes in retinal health and disease.},
journal = {Trends in neurosciences},
volume = {46},
number = {12},
pages = {1067-1082},
pmid = {37848361},
issn = {1878-108X},
support = {R01 EY031594/EY/NEI NIH HHS/United States ; R01 EY032516/EY/NEI NIH HHS/United States ; R01 EY033103/EY/NEI NIH HHS/United States ; R01 EY033765/EY/NEI NIH HHS/United States ; P30 EY008098/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retina ; *Lysosomes/metabolism ; Autophagy/physiology ; Mitochondria/metabolism ; Endocytosis ; },
abstract = {Lysosomes play crucial roles in various cellular processes - including endocytosis, phagocytosis, and autophagy - which are vital for maintaining retinal health. Moreover, these organelles serve as environmental sensors and act as central hubs for multiple signaling pathways. Through communication with other cellular components, such as mitochondria, lysosomes orchestrate the cytoprotective response essential for preserving cellular homeostasis. This coordination is particularly critical in the retina, given its high metabolic rate and susceptibility to photo-oxidative stress. Consequently, impaired lysosomal function and dysregulated communication between lysosomes and other organelles contribute significantly to the pathobiology of major retinal degenerative diseases. This review explores the pivotal role of lysosomes in retinal cells and their involvement in retinal degenerative diseases.},
}
@article {pmid37847167,
year = {2023},
author = {Singh, RP and Amoaku, W and Bandello, F and Chen, FK and Holz, FG and Kodjikian, L and Ruiz-Moreno, JM and Joshi, P and Wykoff, CC},
title = {Diagnosis and Management of Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Delphi Consensus Exercise.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {10},
pages = {589-598},
doi = {10.3928/23258160-20230824-01},
pmid = {37847167},
issn = {2325-8179},
mesh = {Humans ; *Geographic Atrophy/diagnosis/etiology/therapy ; Consensus ; Delphi Technique ; Fluorescein Angiography/methods ; *Macular Degeneration/complications/diagnosis/therapy ; Tomography, Optical Coherence/methods ; Atrophy/complications ; },
abstract = {Geographic atrophy (GA) is a progressive and irreversible retinal disease with no comprehensive recommendations for diagnosis or monitoring. We used a Delphi approach to determine consensus in key areas around diagnosis and management of GA. A steering committee of eight retina specialists developed two sequential online surveys administered to eye care professionals (ECPs). Consensus was defined as agreement by ≥ 75% of respondents. Up to 177 ECPs from eight countries completed one or both surveys. Consensus was achieved in several topics related to diagnostic imaging, including the use of optical coherence tomography, and the urgent need for treatments and beneficial interventions to reduce the associated burden. Currently, low-vision aids and smoking cessation are considered the most beneficial interventions. We demonstrate consensus for diagnosis and management of patients with GA including best practices in patient identification and monitoring, and unmet needs. [Ophthalmic Surg Lasers Imaging Retina 2023;54:589-598.].},
}
@article {pmid37847166,
year = {2023},
author = {Yousuf, SJ and Ma, J and Nelson, L and Chen, M and Weldeslase, TA and Akinyemi, OA},
title = {Neovascular Age-Related Macular Degeneration in a Predominantly Black Population.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {10},
pages = {580-584},
doi = {10.3928/23258160-20230927-01},
pmid = {37847166},
issn = {2325-8179},
mesh = {Humans ; Retina/pathology ; Retrospective Studies ; Cicatrix ; Visual Acuity ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; Ranibizumab ; },
abstract = {BACKGROUND AND OBJECTIVE: We intend to study the characteristics and outcomes of an understudied patient population with neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This retrospective study evaluated presenting features and outcomes in a predominantly Black patient population with nAMD. A multivariate regression explored baseline characteristics predictive of 1-year vision.<br><br>RESULTS: Sixty-three eyes were included. The median (interquartile range) baseline vision was 20/300 (20/80 to counting fingers). Patients' baseline optical coherence tomography findings showed a mean central subfield thickness of 336 &#xb5;m; 80% (n = 35) and 41% (n = 18) had fluid and central scarring, respectively. The primary predictor for vision at year-one was baseline vision (P = 0.03, 95% CI: 0.04 to 0.91). All of those who gained &#x2265; 3 lines of vision lacked central scarring at baseline.<br><br>CONCLUSION: Further studies are needed to investigate how to improve earlier detection and treatment of nAMD in this patient population. [Ophthalmic Surg Lasers Imaging Retina 2023;54:580-584.].},
}
@article {pmid37846994,
year = {2023},
author = {Siag, N and Moshkovsky, R and Golan, N and Nussbaum, L and Bar, A and Malik Gadot, E and Maharshak, I},
title = {AREDS2 Supplementation in Patients with Wet Age-Related Macular Degeneration.},
journal = {The Israel Medical Association journal : IMAJ},
volume = {25},
number = {10},
pages = {669-672},
pmid = {37846994},
issn = {1565-1088},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A/therapeutic use ; Retrospective Studies ; Endothelial Growth Factors/therapeutic use ; Dietary Supplements ; Intravitreal Injections ; Treatment Outcome ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision.<br><br>OBJECTIVES: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD.<br><br>METHODS: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity.<br><br>RESULTS: The average number of injections per patient after 3 years was 21.89 &#xb1; 7.85 in the study group and 26.00 &#xb1; 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 &#xb1; 0.45 and 0.8 &#xb1; 0.73 (P = 0.09), and final central macular thicknesses were 288.26 &#xb1; 55.38 and 313.12 &#xb1; 107.36 (P = 0.38) in the study and control groups, respectively.<br><br>CONCLUSIONS: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.},
}
@article {pmid37846377,
year = {2023},
author = {Li, C and Xiao, C and Tao, H and Tang, X},
title = {Research progress of iron metabolism in retinal diseases.},
journal = {Advances in ophthalmology practice and research},
volume = {3},
number = {2},
pages = {93-100},
pmid = {37846377},
issn = {2667-3762},
abstract = {BACKGROUND: Retinal diseases can lead to severe visual impairment and even blindness, but current treatments are limited. For precise targeted therapy, the pathophysiological mechanisms of the diseases still need to be further explored. Iron serves an essential role in many biological activities and helps maintain the function and morphology of the retina. The vision problems caused by retinal diseases are affecting more and more people, the study of iron metabolism in retinal diseases possesses great potential for clinical application.<br><br>MAIN TEXT: Iron maintains a dynamic balance in the retina but in excess is toxic to the retina. Iron overload can lead to various pathological changes in the retina through oxidative stress, inflammation, cell death, angiogenesis and other pathways. It is therefore involved in the progression of retinal diseases such as age-related macular degeneration, glaucoma, diabetic retinopathy, retinitis pigmentosa, and hereditary iron overload. In recent years, iron chelators have been shown to be effective in the treatment of retinal diseases, but the exact mechanism is not yet fully understood. This question prompted further investigation into the specific mechanisms by which iron metabolism is involved in retinal disease.<br><br>CONCLUSIONS: This review summarizes iron metabolism processes in the retina and mechanistic studies of iron metabolism in the progression of retinal disease. It also highlights the therapeutic potential of iron chelators in retinal diseases.},
}
@article {pmid37846358,
year = {2023},
author = {Liu, H and Cheng, J and Zhuang, X and Qi, B and Li, F and Zhang, B},
title = {Genomic instability and eye diseases.},
journal = {Advances in ophthalmology practice and research},
volume = {3},
number = {3},
pages = {103-111},
pmid = {37846358},
issn = {2667-3762},
abstract = {BACKGROUND: Genetic information is stored in the bases of double-stranded DNA. However, the integrity of DNA molecules is constantly threatened by various mutagenic agents, including pollutants, ultraviolet light (UV), and medications. To counteract these environmental damages, cells have established multiple mechanisms, such as producing molecules to identify and eliminate damaged DNA, as well as reconstruct the original DNA structures. Failure or insufficiency of these mechanisms can cause genetic instability. However, the role of genome stability in eye diseases is still under-researched, despite extensive study in cancer biology.<br><br>MAIN TEXT: As the eye is directly exposed to the external environment, the genetic materials of ocular cells are constantly under threat. Some of the proteins essential for DNA damage repair, such as pRb, p53, and RAD21, are also key during the ocular disease development. In this review, we discuss five ocular diseases that are associated with genomic instability. Retinoblastoma and pterygium are linked to abnormal cell cycles. Fuchs' corneal endothelial dystrophy and age-related macular degeneration are related to the accumulation of DNA damage caused by oxidative damage and UV. The mutation of the subunit of the cohesin complex during eye development is linked to sclerocornea.<br><br>CONCLUSIONS: Failure of DNA damage detection or repair leads to increased genomic instability. Deciphering the role of genomic instability in ocular diseases can lead to the development of new treatments and strategies, such as protecting vulnerable cells from risk factors or intensifying damage to unwanted cells.},
}
@article {pmid37846318,
year = {2023},
author = {Wang, H and Ye, Q and Xu, W and Wang, J and Liu, J and Xu, X and Zhang, W},
title = {Research trends of worldwide ophthalmologic randomized controlled trials in the 21st century: A bibliometric study.},
journal = {Advances in ophthalmology practice and research},
volume = {3},
number = {4},
pages = {159-170},
pmid = {37846318},
issn = {2667-3762},
abstract = {BACKGROUND: Randomized controlled trials (RCTs) are often considered the gold standard and the cornerstone for clinical practice. However, bibliometric studies on worldwide RCTs of ophthalmology published in the 21st century have not been reported in detail yet. This study aims to perform a bibliometric study and visualization analysis of worldwide ophthalmologic RCTs in the 21st century.<br><br>METHODS: Global ophthalmologic RCTs from 2000 to 2022 were searched in the Web of Science Core Collection. The number of publications, country/region, institution, author, journal, and research hotspots of RCTs were analyzed using HistCite, VOSviewer, CiteSpace, and Excel software.<br><br>RESULTS: 2366 institutions and 90 journals from 83 countries/regions participated in the publication of 1769 global ophthalmologic RCTs, with the United States leading in the number of volumes and research field, and the Moorfields Eye Hospital contributing to the most publications. Ophthalmology received the greatest number of publications and co-citations. Jeffrey S. Heier owned the most publications and Jost B. Jonas owned the most co-citations. The knowledge foundations of global ophthalmologic RCTs were mainly retinopathy, glaucoma, dry eye disease (DED), and cataracts, and anti-vascular endothelial growth factor (VEGF) therapy (ranibizumab), topical ocular hypotensive medication, laser trabeculoplasty. Anti-VEGF therapy for age-related macular degeneration (AMD), DME (diabetic macular edema), and DED, the use of new diagnostic tools, and myopia were the hottest research highlights. Anti-VEGF therapy, prompt laser, triamcinolone, and verteporfin photodynamic therapy for AMD, DME, and CNV (choroidal neovascularization), DED, myopia, and open-angle glaucoma were the research hotspots with the longest duration. The future research hotspots might be DED and the prevention and control of myopia.<br><br>CONCLUSIONS: Overall, the number of global ophthalmologic RCTs in the 21st century was keeping growing, there was an imbalance between the regions and institutions, and more efforts are required to raise the quantity, quality, and global impact of high-quality clinical evidence in developing countries/regions.},
}
@article {pmid37844999,
year = {2024},
author = {Finn, M and Baldwin, G and Garg, I and Wescott, HE and Koch, T and Vingopoulos, F and Zeng, R and Choi, H and Sayah, D and Husain, D and Patel, NA and Kim, LA and Miller, JW and Wu, DM and Vavvas, DG and Miller, JB},
title = {Comparative study of widefield swept-source optical coherence tomography angiography in eyes with concomitant age-related macular degeneration and diabetic retinopathy.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {7},
pages = {963-970},
doi = {10.1136/bjo-2023-323792},
pmid = {37844999},
issn = {1468-2079},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Cross-Sectional Studies ; *Diabetic Retinopathy/diagnosis/diagnostic imaging ; *Fluorescein Angiography/methods ; Aged ; Middle Aged ; *Retinal Vessels/diagnostic imaging/pathology ; Macular Degeneration/complications ; Visual Acuity/physiology ; Fundus Oculi ; Aged, 80 and over ; Retrospective Studies ; },
abstract = {BACKGROUND/AIMS: We sought to evaluate widefield swept-source optical coherence tomography angiography (WF SS-OCTA) among eyes with concomitant age-related macular degeneration (AMD) and diabetes mellitus or diabetic retinopathy (DM/DR).<br><br>METHODS: This cross-sectional, comparative study consisted of three study groups: eyes with (1) AMD and DM/DR, (2) AMD alone and (3) DM/DR alone. WF SS-OCTA (3&#xd7;3, 6&#xd7;6 and 12&#xd7;12&#x2009;mm) images were captured. Vascular metrics included foveal avascular zone (FAZ), vessel density (VD) and vessel skeletonised density (VSD). Mixed-effects multivariable regression models adjusted for age were performed by cohort and subgroup based on AMD and DR stages.<br><br>RESULTS: Our cohort included 287 eyes from 186 patients with an average age of 64&#xb1;14.0 years old. Results revealed significantly reduced vascular metrics in concomitant AMD and DM/DR eyes (N=68) compared with AMD-only eyes (N=71) on all angiograms but not compared with DM/DR-only eyes (N=148). For example, when compared with AMD-only eyes, AMD and DM/DR eyes had significantly reduced VD (&#x3b2;=-0.03, p=0.016) and VSD (&#x3b2;=-1.09, p=0.022) on 12&#xd7;12&#x2009;mm angiograms, increased FAZ perimeter (&#x3b2;=0.51, p=0.025) and FAZ area (&#x3b2;=0.11, p=0.015) on 6&#xd7;6&#x2009;mm angiogram, and reductions in all VD and VSD metrics on 3&#xd7;3&#x2009;and 6&#xd7;6&#x2009;mm angiograms. However, only 3&#xd7;3&#x2009;mm angiogram FAZ metrics were significantly different when comparing DM/DR eyes with concomitant AMD and DM/DR eyes.<br><br>CONCLUSION: WF SS-OCTA revealed significant reductions in retinal microvasculature metrics in AMD and DM/DR eyes compared with AMD-only eyes but not compared with DM/DR-only eyes.},
}
@article {pmid37843230,
year = {2024},
author = {Li, X and Li, C and Huang, H and Bai, D and Wang, J and Chen, A and Gong, Y and Leng, Y},
title = {Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial.},
journal = {Neural regeneration research},
volume = {19},
number = {4},
pages = {923-928},
pmid = {37843230},
issn = {1673-5374},
abstract = {The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells, affecting vision. The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation. However, although the macular thickness can be normalized with each of these two therapies used alone, the vision does not improve in many patients. This might result from the incomplete recovery of retinal ganglion cell injury. Therefore, a prospective, non-randomized, controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery. In this trial, 150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods, followed by treatment with anti-vascular endothelial growth factor drugs, laser photocoagulation therapy, and their combination. All patients will be followed up for 12 months. The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment. The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1, 3, 6, and 9 months after treatment, retinal nerve fiber layer thickness, best-corrected visual acuity, macular area thickness, and choroidal thickness before and 1, 3, 6, 9, and 12 months after treatment. Safety measure is the incidence of adverse events at 1, 3, 6, 9, and 12 months after treatment. The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period. The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity. The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No. (2023)(26) on April 25, 2023, and was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2300072478, June 14, 2023, protocol version: 2.0).},
}
@article {pmid37840684,
year = {2023},
author = {Amini, MA and Karbasi, A and Vahabirad, M and Khanaghaei, M and Alizamir, A},
title = {Mechanistic Insight into Age-Related Macular Degeneration (AMD): Anatomy, Epidemiology, Genetics, Pathogenesis, Prevention, Implications, and Treatment Strategies to Pace AMD Management.},
journal = {Chonnam medical journal},
volume = {59},
number = {3},
pages = {143-159},
pmid = {37840684},
issn = {2233-7385},
abstract = {One of the most complicated eye disorders is age-related macular degeneration (AMD) which is the leading cause of irremediable blindness all over the world in the elderly. AMD is classified as early stage to late stage (advanced AMD), in which this stage is divided into the exudative or neovascular form (wet AMD) and the nonexudative or atrophic form (dry AMD). Clinically, AMD primarily influences the central area of retina known as the macula. Importantly, the wet form is generally associated with more severe vision loss. AMD has a systemic component, where many factors, like aging, genetic, environment, autoimmune and non-autoimmune disorders are associated with this disease. Additionally, healthy lifestyles, regular exercise, maintaining a normal lipid profile and weight are crucial to decreasing the risk of AMD. Furthermore, therapeutic strategies for limiting AMD should encompass a variety of factors to avoid and improve drug interventions, and also need to take into account personalized genetic information. In conclusion, with the development of technology and research progress, visual impairment and legal blindness from AMD have been substantially reduced in incidence. This review article is focused on identifying and developing the knowledge about the association between genetics, and etiology with AMD. We hope that this review will encourage researchers and lecturers, open new discussions, and contribute to a better understanding of AMD that improves patients' visual acuity, and upgrades the quality of life of AMD patients.},
}
@article {pmid37840667,
year = {2023},
author = {Sasseville, S and Karami, S and Tchatchouang, A and Charpentier, P and Anney, P and Gobert, D and Proulx, S},
title = {Biomaterials used for tissue engineering of barrier-forming cell monolayers in the eye.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {11},
number = {},
pages = {1269385},
pmid = {37840667},
issn = {2296-4185},
abstract = {Cell monolayers that form a barrier between two structures play an important role for the maintenance of tissue functionality. In the anterior portion of the eye, the corneal endothelium forms a barrier that controls fluid exchange between the aqueous humor of the anterior chamber and the corneal stroma. This monolayer is central in the pathogenesis of Fuchs endothelial corneal dystrophy (FECD). FECD is a common corneal disease, in which corneal endothelial cells deposit extracellular matrix that increases the thickness of its basal membrane (Descemet's membrane), and forms excrescences (guttae). With time, there is a decrease in endothelial cell density that generates vision loss. Transplantation of a monolayer of healthy corneal endothelial cells on a Descemet membrane substitute could become an interesting alternative for the treatment of this pathology. In the back of the eye, the retinal pigment epithelium (RPE) forms the blood-retinal barrier, controlling fluid exchange between the choriocapillaris and the photoreceptors of the outer retina. In the retinal disease dry age-related macular degeneration (dry AMD), deposits (drusen) form between the RPE and its basal membrane (Bruch's membrane). These deposits hinder fluid exchange, resulting in progressive RPE cell death, which in turn generates photoreceptor cell death, and vision loss. Transplantation of a RPE monolayer on a Bruch's membrane/choroidal stromal substitute to replace the RPE before photoreceptor cell death could become a treatment alternative for this eye disease. This review will present the different biomaterials that are proposed for the engineering of a monolayer of corneal endothelium for the treatment of FECD, and a RPE monolayer for the treatment of dry AMD.},
}
@article {pmid37840275,
year = {2024},
author = {Kha, R and Wen, Q and Bender, N and Jones, C and Gopinath, B and Macniven, R and Tang, D},
title = {Understanding barriers and enablers to participation in a proposed online lifestyle intervention for older adults with age-related macular degeneration to guide programme implementation.},
journal = {Journal of health psychology},
volume = {29},
number = {4},
pages = {317-331},
pmid = {37840275},
issn = {1461-7277},
mesh = {Humans ; Aged ; *Life Style ; Qualitative Research ; Healthy Lifestyle ; Health Services Accessibility ; *Macular Degeneration/prevention &amp; control ; },
abstract = {Age-related macular degeneration (AMD) is a blinding condition associated with depression, loneliness and unhealthy lifestyle behaviours which drives AMD progression. We have proposed the first online lifestyle intervention for AMD, called Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) to promote positive lifestyle changes and reduce loneliness. This qualitative grounded-theory study explored enablers and barriers to future participation in MINGLE for older adults with AMD. Thirty-one participants were interviewed and thematic analysis revealed nine themes. Enablers to participation were: socialising and learning about AMD, motivation to improve health, programme accessibility and structure. Barriers were: lack of time, technology, limited knowledge regarding holistic interventions, vision-related issues, mobility and negative perception of group interactions. These factors must be considered when developing lifestyle interventions for AMD patients to maximise participation. Supporting technology use and raising awareness about benefits of healthy lifestyle behaviours for AMD may help overcome these barriers.},
}
@article {pmid37839548,
year = {2024},
author = {Csincsik, L and Muldrew, KA and Bettiol, A and Wright, DM and Rosenfeld, PJ and Waheed, NK and Empeslidis, T and De Cock, E and Yamaguchi, TCN and Hogg, RE and Peto, T and Chakravarthy, U},
title = {The Double Layer Sign Is Highly Predictive of Progression to Exudation in Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {3},
pages = {234-245},
doi = {10.1016/j.oret.2023.10.006},
pmid = {37839548},
issn = {2468-6530},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnosis ; *Choroidal Neovascularization/drug therapy ; },
abstract = {PURPOSE: The presences of a double layer sign (DLS) and a shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) were investigated using spectral domain-OCT (SD-OCT) imaging to determine their ability to predict progression to exudative macular neovascularization (eMNV) in the unaffected fellow eyes (study eye) of participants with age-related macular degeneration (AMD) with newly diagnosed unilateral eMNV.<br><br>DESIGN: Retrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU).<br><br>PARTICIPANTS: The EDNA study repository of SD-OCT scans was assessed for inclusion. Cases with incomplete data sets, low quality scans, or exhibiting other pathology were excluded, which resulted in 459 eligible cases.<br><br>METHODS: Spectral domain-OCT volume scans of study eyes were graded for irregular elevation of the RPE (IE), with length, and height measurements made on the most affected B-scan. Eyes with heterogeneous reflectivity within the IE were classified as exhibiting the DLS. Eyes with DLS where the length of separation between RPE and Bruch's membrane was &#x2265; 1000 &#x3bc;m in length and < 100 &#x3bc;m in height were subclassified as SIRE.<br><br>MAIN OUTCOME MEASURES: Hazard of progression to eMNV for DLS and SIRE.<br><br>RESULTS: Of the 459 eyes, 268 had IE, of which 101 were DLS-like and 51 also fulfilled criteria for SIRE. Over the 3 years FU period, 104 (23%) eyes progressed to eMNV. After an FU of 18 months, a significantly higher proportion of study eyes (P < 0.001) with IE, DLS, and SIRE developed eMNV compared with those without these features (IE: 17% vs. no IE 6.3%; DLS: 23% vs. no DLS 9.9%; SIRE: 22% vs. no SIRE 11%). In the adjusted Cox regression models, a significantly greater hazard of progression (P < 0.001) was associated with the presence of IE (adjusted hazard ratio [HR], 3.01; 95% confidence interval [CI], 1.88-4.82), DLS (adjusted HR, 3.41; 95% CI, 2.26-5.14), or SIRE (adjusted HR, 2.83; 95% CI, 1.68-4.75).<br><br>CONCLUSION: The DLS is a highly sensitive predictor of progression to eMNV, and the use of SIRE does not improve predictability.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37838654,
year = {2023},
author = {Karg, MM and Moorefield, M and Hoffmann, E and Philipose, H and Krasniqi, D and Hoppe, C and Shu, DY and Shirahama, S and Ksander, BR and Saint-Geniez, M},
title = {Microglia preserve visual function loss in the aging retina by supporting retinal pigment epithelial health.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {20},
number = {1},
pages = {53},
pmid = {37838654},
issn = {1742-4933},
support = {P30 EY003790/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND: Increased age is a risk factor for the development and progression of retinal diseases including age-related macular degeneration (AMD). Understanding the changes that occur in the eye due to aging is important in enhancing our understanding of AMD pathogenesis and the development of novel AMD therapies. Microglia, the resident brain and retinal immune cells are associated with both maintaining homeostasis and protection of neurons and loss of microglia homeostasis could be a significant player in age related neurodegeneration. One important characteristic of retinal aging is the migration of microglia from the inner to outer retina where they reside in the subretinal space (SRS) in contact with the retinal pigment epithelial (RPE) cells. The role of aged subretinal microglia is unknown. Here, we depleted microglia in aged C57/BL6 mice fed for 6 weeks with a chow containing PLX5622, a small molecule inhibitor of colony-stimulating factor-1 receptor (Csf1r) required for microglial survival.<br><br>RESULTS: The subretinal P2RY12&#x2009;+&#x2009;microglia in aged mice displayed a highly amoeboid and activated morphology and were filled with autofluorescence droplets reminiscent of lipofuscin. TEM indicates that subretinal microglia actively phagocytize shed photoreceptor outer segments, one of the main functions of retinal pigmented epithelial cells. PLX5622 treatment depleted up to 90% of the retinal microglia and was associated with significant loss in visual function. Mice on the microglia depletion diet showed reduced contrast sensitivity and significantly lower electroretinogram for the c-wave, a measurement of RPE functionality, compared to age-matched controls. The loss of c-wave coincided with a loss of RPE cells and increased RPE swelling in the absence of microglia.<br><br>CONCLUSIONS: We conclude that microglia preserve visual function in aged mice and support RPE cell function, by phagocytosing shed photoreceptor outer segments and lipids, therefore compensating for the known age-related decline of RPE phagocytosis.},
}
@article {pmid37838498,
year = {2024},
author = {Caspers, S and Abramowicz, S and Pasteels, B and Postelmans, L},
title = {Smoking and short-term response to intravitreal anti-Vascular Endothelial Growth Factor injections in neovascular age-related macular degeneration.},
journal = {Journal francais d'ophtalmologie},
volume = {47},
number = {1},
pages = {103955},
doi = {10.1016/j.jfo.2023.04.010},
pmid = {37838498},
issn = {1773-0597},
mesh = {Humans ; Male ; Female ; Aged ; Aged, 80 and over ; *Angiogenesis Inhibitors/adverse effects ; Ranibizumab/adverse effects ; Endothelial Growth Factors ; Retrospective Studies ; Case-Control Studies ; Smoking/adverse effects/epidemiology ; Vascular Endothelial Growth Factor A ; Treatment Outcome ; Receptors, Vascular Endothelial Growth Factor ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; },
abstract = {PURPOSE: To evaluate the role of smoking status on the response to three monthly intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) injections in treatment-naive neovascular AMD (nAMD) patients.<br><br>METHODS: We conducted a single-center, retrospective, case-control cohort study in Belgium.<br><br>RESULTS: Intravitreal treatment (IVT) was performed in 147 eyes of 131 patients, including 92 females (70%). Mean age at the time of the first IVT was 79&#xb1;9 years. Seventeen patients (13%) were actively smoking at the time of the anti-VEGF IVT. On average, active smokers were 11 years younger than non-smokers when starting IVT treatment. They also showed more frequent subretinal fluid than non-smokers (94% vs. 65%). Mann-Whitney analyses comparing change in central macular thickness and change in logarithm of the minimum angle of resolution visual acuity between active smokers and non-smokers showed no significant difference in treatment response between both groups. Likewise, no significant difference was found when comparing treatment response between patients with less than 10 pack-years (PY) (including never-smokers) and patients with over 10 PY. In a binary logistic regression model, male patients responded worse to anti-VEGF IVT than their female counterparts, with an odds ratio (OR) of 0.27 for good response. This was the only statistically significant predictor of treatment response.<br><br>CONCLUSION: Our study failed to demonstrate an effect of smoking on the short-term treatment response to anti-VEGF in nAMD.},
}
@article {pmid37834872,
year = {2023},
author = {Wang, L and Shah, SM and Mangwani-Mordani, S and Gregori, NZ},
title = {Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease.},
journal = {Journal of clinical medicine},
volume = {12},
number = {19},
pages = {},
pmid = {37834872},
issn = {2077-0383},
abstract = {Autosomal recessive Stargardt disease (STGD1) is an inherited retinal degenerative disease associated with a mutated ATP-binding cassette, subfamily A, member 4 (ABCA4) gene. STGD1 is the most common form of juvenile macular degeneration with onset in late childhood to early or middle adulthood and causes progressive, irreversible visual impairment and blindness. No effective treatment is currently available. In the present article, we review the most recent updates in clinical trials targeting the management of STGD1, including gene therapy, small molecule therapy, and stem cell therapy. In gene therapy, dual adeno-associated virus and non-viral vectors have been successful in delivering the human ABCA4 gene in preclinical studies. For pharmaceutical therapies ALK-001, deuterated vitamin A shows promise with preliminary data for phase 2 trial, demonstrating a decreased atrophy growth rate after two years. Stem cell therapy using human pluripotent stem cell-derived retinal pigment epithelium cells demonstrated long-term safety three years after implantation and visual acuity improvements in the first two years after initiation of therapy. Many other treatment options have ongoing investigations and clinical trials. While multiple potential interventions have shown promise in attenuating disease progression, further exploration is necessary to demonstrate treatment safety and efficacy.},
}
@article {pmid37834856,
year = {2023},
author = {Bhat, M and Shirzad, S and Fofana, AK and Gobeil, F and Couture, R and Vaucher, E},
title = {Prevention of Inflammation, Neovascularization, and Retinal Dysfunction by Kinin B1 Receptor Antagonism in a Mouse Model of Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {19},
pages = {},
pmid = {37834856},
issn = {2077-0383},
support = {PJT-175061/CAPMC/CIHR/Canada ; },
abstract = {The kallikrein-kinin system (KKS) contributes to vascular inflammation and neovascularization in age-related macular degeneration (AMD), particularly via the kinin B1 receptor (B1R). The aim of the present study was to determine the protective effects of the topical administration of the B1R antagonist (R-954) on inflammation, neovascularization, and retinal dysfunction in a murine model of neovascular AMD. Choroidal neovascularization (CNV) was induced in C57BL6 mice using an argon laser. A treatment with ocular drops of R-954 (100 μg/15 μL, twice daily in both eyes), or vehicle, was started immediately on day 0, for 7, 14, or 21 days. CNV, invasive microglia, and B1R immunoreactive glial cells, as well as electroretinography alterations, were observed within the retina and choroid of the CNV group but not in the control group. The staining of B1R was abolished by R-954 treatment as well as the proliferation of microglia. R-954 treatment prevented the CNV development (volume: 20 ± 2 vs. 152 ± 5 × 10[4] µm[3] in R-954 vs. saline treatment). R-954 also significantly decreased photoreceptor and bipolar cell dysfunction (a-wave amplitude: -47 ± 20 vs. -34 ± 14 µV and b-wave amplitude: 101 ± 27 vs. 64 ± 17 µV in R-954 vs. saline treatment, day 7) as well as angiogenesis tufts in the retina. These results suggest that self-administration of R-954 by eye-drop treatment could be a promising therapy in AMD to preserve retinal health and vision.},
}
@article {pmid37833663,
year = {2023},
author = {Gu, J and Lei, C and Zhang, M},
title = {Folate and retinal vascular diseases.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {413},
pmid = {37833663},
issn = {1471-2415},
support = {ZYJC21025//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; ZYJC21025//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; ZYJC21025//1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University/ ; },
mesh = {Humans ; Folic Acid/therapeutic use ; *Hyperhomocysteinemia/complications ; Endothelial Cells/metabolism ; Methionine ; *Diabetic Retinopathy ; Glucose ; Homocysteine ; },
abstract = {Folate, a pteroylglutamic acid derivative, participates in fundamental cellular metabolism. Homocysteine, an amino acid, serves as an intermediate of the methionine cycle and can be converted back to methionine. Hyperhomocysteinemia is a recognized risk factor for atherosclerotic and cardiovascular diseases. In recent decades, elevated plasma homocysteine levels and low folate status have been observed in many patients with retinal vascular diseases, such as retinal vascular occlusions, diabetic retinopathy, and age-related degeneration. Homocysteine-induced toxicity toward vascular endothelial cells might participate in the formation of retinal vascular diseases. Folate is an important dietary determinant of homocysteine. Folate deficiency is the most common cause of hyperhomocysteinemia. Folate supplementation can eliminate excess homocysteine in plasma. In in vitro experiments, folic acid had a protective effect on vascular endothelial cells against high glucose. Many studies have explored the relationship between folate and various retinal vascular diseases. This review summarizes the most important findings that lead to the conclusion that folic acid supplementation might be a protective treatment in patients with retinal vascular diseases with high homocysteine or glucose status. More research is still needed to validate the effect of folate and its supplementation in retinal vascular diseases.},
}
@article {pmid37833348,
year = {2023},
author = {von der Emde, L and Mallwitz, M and Vaisband, M and Hasenauer, J and Saßmannshausen, M and Terheyden, JH and , and Sloan, KR and Schmitz-Valckenberg, S and Finger, RP and Holz, FG and Ach, T},
title = {Retest variability and patient reliability indices of quantitative fundus autofluorescence in age-related macular degeneration: a MACUSTAR study report.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {17417},
pmid = {37833348},
issn = {2045-2322},
support = {R01 EY027948/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Reproducibility of Results ; *Retinal Pigment Epithelium ; Fluorescein Angiography/methods ; Fundus Oculi ; *Macular Degeneration/diagnostic imaging ; },
abstract = {This study aimed to determine the retest variability of quantitative fundus autofluorescence (QAF) in patients with and without age-related macular degeneration (AMD) and evaluate the predictive value of patient reliability indices on retest reliability. A total of 132 eyes from 68 patients were examined, including healthy individuals and those with various stages of AMD. Duplicate QAF imaging was conducted at baseline and 2 weeks later across six study sites. Intraclass correlation (ICC) analysis was used to evaluate the consistency of imaging, and mean opinion scores (MOS) of image quality were generated by two researchers. The contribution of MOS and other factors to retest variation was assessed using mixed-effect linear models. Additionally, a Random Forest Regressor was trained to evaluate the extent to which manual image grading of image quality could be replaced by automated assessment (inferred MOS). The results showed that ICC values were high for all QAF images, with slightly lower values in AMD-affected eyes. The average inter-day ICC was found to be 0.77 for QAF segments within the QAF8 ring and 0.74 for peripheral segments. Image quality was predicted with a mean absolute error of 0.27 on a 5-point scale, and of all evaluated reliability indices, MOS/inferred MOS proved most important. The findings suggest that QAF allows for reliable testing of autofluorescence levels at the posterior pole in patients with AMD in a multicenter, multioperator setting. Patient reliability indices could serve as eligibility criteria for clinical trials, helping identify patients with adequate retest reliability.},
}
@article {pmid37831941,
year = {2024},
author = {Goh, KL and Wintergerst, MWM and Abbott, CJ and Hadoux, X and Jannaud, M and Kumar, H and Hodgson, LAB and Guzman, G and Janzen, S and van Wijngaarden, P and Finger, RP and Guymer, RH and Wu, Z},
title = {HYPERREFLECTIVE FOCI NOT SEEN AS HYPERPIGMENTARY ABNORMALITIES ON COLOR FUNDUS PHOTOGRAPHS IN AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {2},
pages = {214-221},
doi = {10.1097/IAE.0000000000003958},
pmid = {37831941},
issn = {1539-2864},
support = {APP1027624//National Health and Medical Research Council/ ; GNT1194667//National Health and Medical Research Council/ ; #2008382//National Health and Medical Research Council/ ; M2019073//BrightFocus Foundation/ ; 3/22//Ernst und Berta Grimmke Stiftung/ ; },
mesh = {Humans ; *Macular Degeneration/diagnosis ; Retina ; Fundus Oculi ; Diagnostic Techniques, Ophthalmological ; Prognosis ; Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis ; },
abstract = {PURPOSE: To investigate the prognostic value of quantifying optical coherence tomography (OCT)-defined hyperreflective foci (HRF) that do not correspond to hyperpigmentary abnormalities (HPAs) on color fundus photographs (CFPs)-HRF (OCT+/CFP-) -when considered in addition to HPA extent, for predicting late age-related macular degeneration development. This study sought to understand the impact of HRF (OCT+/CFP-) extent on visual sensitivity.<br><br>METHODS: Two hundred eighty eyes from 140 participants with bilateral large drusen underwent imaging and microperimetry at baseline, and then 6-monthly for 3-years. The extent of HPAs on CFPs and HRF (OCT+/CFP-) on OCT was quantified at baseline. Predictive models for progression to late age-related macular degeneration, accounting for drusen volume and age, were developed using HPA extent, with and without HRF (OCT+/CFP-) extent. The association between HPA and HRF (OCT+/CFP-) extent with sector-based visual sensitivity was also evaluated.<br><br>RESULTS: Incorporating HRF (OCT+/CFP-) extent did not improve the predictive performance for late age-related macular degeneration development (P &#x2265; 0.32). Increasing HPA and HRF (OCT+/CFP-) extent in each sector were independently and significantly associated with reduced sector-based visual sensitivity (P &#x2264; 0.004).<br><br>CONCLUSION: The addition of HRF (OCT+/CFP-) extent to HPA extent did not improve the prediction of late age-related macular degeneration development. HRF (OCT+/CFP-) extent was also independently associated with local reductions in visual sensitivity, after accounting for HPAs.},
}
@article {pmid37831763,
year = {2023},
author = {Choi, W and Nensel, AK and Droho, S and Fattah, MA and Mokashi-Punekar, S and Swygart, DI and Burton, ST and Schwartz, GW and Lavine, JA and Gianneschi, NC},
title = {Thrombospondin-1 proteomimetic polymers exhibit anti-angiogenic activity in a neovascular age-related macular degeneration mouse model.},
journal = {Science advances},
volume = {9},
number = {41},
pages = {eadi8534},
pmid = {37831763},
issn = {2375-2548},
support = {R01 EY034486/EY/NEI NIH HHS/United States ; R01 EY031029/EY/NEI NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; K08 EY030923/EY/NEI NIH HHS/United States ; R01 EY031329/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Humans ; *Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; Thrombospondin 1/therapeutic use ; *Macular Degeneration/drug therapy ; Peptides ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the developed world. Current therapy includes monthly intraocular injections of anti-VEGF antibodies, which are ineffective in up to one third of patients. Thrombospondin-1 (TSP1) inhibits angiogenesis via CD36 binding, and its down-regulated expression is negatively associated with the onset of nAMD. Here, we describe TSP1 mimetic protein-like polymers (TSP1 PLPs). TSP1 PLPs bind CD36 with high affinity, resist degradation, show prolonged intraocular half-lives (13.1 hours), have no toxicity at relevant concentrations in vivo (40 μM), and are more efficacious in ex vivo choroidal sprouting assays compared to the peptide sequence and Eylea (aflibercept), the current standard of care anti-VEGF treatment. Furthermore, PLPs exhibit superior in vivo efficacy in a mouse model for nAMD compared to control PLPs consisting of scrambled peptide sequences, using fluorescein angiography and immunofluorescence. Since TSP-1 inhibits angiogenesis by VEGF-dependent and independent mechanisms, TSP1 PLPs are a potential therapeutic for patients with anti-VEGF treatment-resistant nAMD.},
}
@article {pmid37831740,
year = {2023},
author = {Bhuckory, MB and Wang, BY and Chen, ZC and Shin, A and Huang, T and Galambos, L and Vounotrypidis, E and Mathieson, K and Kamins, T and Palanker, D},
title = {Cellular migration into a subretinal honeycomb-shaped prosthesis for high-resolution prosthetic vision.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {42},
pages = {e2307380120},
pmid = {37831740},
issn = {1091-6490},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; R01 EY027786/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Rats ; Animals ; *Visual Prosthesis ; Prosthesis Implantation ; Retina/physiology ; Vision, Ocular ; *Porifera ; *Retinal Neurons ; Electric Stimulation ; },
abstract = {In patients blinded by geographic atrophy, a subretinal photovoltaic implant with 100 µm pixels provided visual acuity closely matching the pixel pitch. However, such flat bipolar pixels cannot be scaled below 75 µm, limiting the attainable visual acuity. This limitation can be overcome by shaping the electric field with 3-dimensional (3-D) electrodes. In particular, elevating the return electrode on top of the honeycomb-shaped vertical walls surrounding each pixel extends the electric field vertically and decouples its penetration into tissue from the pixel width. This approach relies on migration of the retinal cells into the honeycomb wells. Here, we demonstrate that majority of the inner retinal neurons migrate into the 25 µm deep wells, leaving the third-order neurons, such as amacrine and ganglion cells, outside. This enables selective stimulation of the second-order neurons inside the wells, thus preserving the intraretinal signal processing in prosthetic vision. Comparable glial response to that with flat implants suggests that migration and separation of the retinal cells by the walls does not cause additional stress. Furthermore, retinal migration into the honeycombs does not negatively affect its electrical excitability, while grating acuity matches the pixel pitch down to 40 μm and reaches the 27 μm limit of natural resolution in rats with 20 μm pixels. These findings pave the way for 3-D subretinal prostheses with pixel sizes of cellular dimensions.},
}
@article {pmid37824807,
year = {2024},
author = {Sarraf, D and Khanani, AM and Sadda, SR and Chang, A and Wong, DT and Kempf, AS and Saffar, I and Tang, S and Tadayoni, R},
title = {PIGMENT EPITHELIAL DETACHMENT THICKNESS AND VARIABILITY AFFECTS VISUAL OUTCOMES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {1},
pages = {10-19},
doi = {10.1097/IAE.0000000000003935},
pmid = {37824807},
issn = {1539-2864},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Retinal Pigment Epithelium ; Visual Acuity ; Intravitreal Injections ; *Retinal Detachment/diagnosis/drug therapy/etiology ; Tomography, Optical Coherence/methods ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/therapeutic use ; *Wet Macular Degeneration/complications/diagnosis/drug therapy ; },
abstract = {PURPOSE: To evaluate the impact of pigment epithelial detachment (PED) thickness (i.e., height) and thickness variability on best-corrected visual acuity outcomes in patients with neovascular age-related macular degeneration in the Phase 3 HAWK and HARRIER trials.<br><br>METHODS: Optical coherence tomography images from the pooled brolucizumab 6 mg and aflibercept 2 mg arms were analyzed for the maximum PED thickness across the macula at baseline through to week 96. Best-corrected visual acuity outcomes were compared in patients with different PED thickness and variability cut-off thresholds.<br><br>RESULTS: Greater PED thickness at baseline or at week 12 was associated with lower mean best-corrected visual acuity gain from baseline to week 96 (baseline PED &#x2265;200 &#xb5; m: +4.6 letters; <200 &#xb5; m: +7.0 letters; week 12 PED &#x2265;100 &#xb5; m: +5.6 letters; <100 &#xb5; m: +6.6 letters). Eyes with the largest PED thickness variability from week 12 through week 96 gained fewer letters from baseline at week 96 (&#x2265;33 &#xb5; m: +3.3 letters; <9 &#xb5; m: +6.2 letters). Furthermore, increased PED thickness at week 48 was associated with higher prevalence of intraretinal and subretinal fluid.<br><br>CONCLUSION: In this treatment-agnostic analysis, greater PED thickness and PED thickness variability were associated with poorer visual outcomes in patients with neovascular age-related macular degeneration and greater neovascular activity.},
}
@article {pmid37822089,
year = {2024},
author = {Reddington, AR and Weir, SO},
title = {Incorporating special needs simulations into allied dental education curriculum to encourage inclusion, understanding, and empathy: A mixed method study.},
journal = {Journal of dental education},
volume = {88},
number = {1},
pages = {16-22},
doi = {10.1002/jdd.13386},
pmid = {37822089},
issn = {1930-7837},
mesh = {Humans ; *Empathy ; *Dentists ; Professional Role ; Curriculum ; Education, Dental ; Dental Hygienists/education ; },
abstract = {OBJECTIVES: Allied dental practitioners increasingly encounter demands specific to treating patients with special needs and disabilities. New standards by the Commission on Dental Accreditation require dental and allied dental graduates to have didactic and skill-based competencies to ensure awareness of and effective treatment and recommendations for these patients. This study sought to determine if adding a special needs simulation activity into allied dental students' curriculum would increase the student's awareness of and comfort level when treating patients with special needs.<br><br>METHODS: This mixed-methods study measures student perceptions specific to the efficacy of adding special needs simulations into the allied dental program curriculum. Graduating dental assistants and dental hygienists (n&#xa0;=&#xa0;65) participated and were paired within their cohort. Didactic instruction specific to the diagnoses of cerebrovascular accident (CVA), macular degeneration, rheumatoid arthritis, schizophrenia, and hearing impairment was provided. Following formal classroom instruction, pairs of students participated in simulation stations, one for each of the listed diagnoses. A pre-/postsurvey was given to evaluate any changes in student perceptions of patients with special needs, and a Student Evaluation of Educational Quality (SEEQ) postsurvey provided to evaluate their perception of the educational activity.<br><br>RESULTS: All 65 participants completed the pre- and postsurveys for a 100% response rate, and 61 (93.8%) completed the SEEQ. SPSS software was utilized to run a Wilcoxen Signed Ranks Test to determine significance for each pre-/postsurvey question to determine any statistically significant (p&#xa0;<&#xa0;.05) differences. Means and standard deviations were calculated for each survey item including SEEQ. There were significant differences for each question, and, overall, in participant's perceptions from the presurvey to the postsurvey. Most notable were the positive changes related to the participants' ability to relate to persons with special needs, their awareness of various special needs, and their increased knowledge of available adaptive oral health equipment.<br><br>CONCLUSION: In conclusion, students feel better prepared to treat clients with special needs after guided instruction within their respected dental hygiene and/or dental assisting programs. The incorporation of lecture and lab content through simulated activities enhances their perceptions, confidence, and preparedness to effectively treat, accommodate, and educate special needs patient's.},
}
@article {pmid37819682,
year = {2023},
author = {Liang, J and Yao, F and Fang, D and Chen, L and Zou, Z and Feng, L and Zhuang, Y and Xie, T and Wei, P and Li, P and Zhang, S},
title = {Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {37},
number = {11},
pages = {e23250},
doi = {10.1096/fj.202301273RR},
pmid = {37819682},
issn = {1530-6860},
mesh = {Animals ; *AMP-Activated Protein Kinases/metabolism ; Apoptosis ; Cellular Senescence ; Disease Models, Animal ; Methylnitrosourea/toxicity ; Photoreceptor Cells, Vertebrate/metabolism ; Retina/metabolism ; *Retinal Degeneration/chemically induced/drug therapy/prevention &amp; control ; },
abstract = {Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated β-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.},
}
@article {pmid37819604,
year = {2023},
author = {Schultheiss, M and Haritoglou, C and Boneva, S and Binder, S and Sebag, J},
title = {[Vitreous body in the treatment of exudative age-related macular degeneration : The medium is the message].},
journal = {Die Ophthalmologie},
volume = {120},
number = {10},
pages = {999-1003},
pmid = {37819604},
issn = {2731-7218},
mesh = {Humans ; Vitreous Body ; *Vitreous Detachment ; *Retinal Diseases ; Vascular Endothelial Growth Factor A/therapeutic use ; *Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: Intravitreal anti-vascular endothelial growth factor (VEGF) is the standard treatment for exudative age-related macular degeneration (AMD). The constitution of the vitreomacular interface varies greatly in cases of attached (with or without traction) or detached vitreous body, which can impact the effectiveness of the anti-VEGF treatment.<br><br>OBJECTIVE: Based on the current literature this article displays the current state of the science on whether the constitution of the vitreous body has an effect on the anti-VEGF treatment.<br><br>MATERIAL AND METHODS: The published data extracted from current trials and post hoc analyses concerning this topic are presented and put into the clinical context.<br><br>RESULTS: The presence of a vitreomacular adhesion reduces the efficacy of anti-VEGF treatment of exudative AMD. Posterior vitreous body detachment represents a&#xa0;positive prognostic factor concerning the efficacy of anti-VEGF treatment but not necessarily the prognosis for visual acuity.<br><br>CONCLUSION: Patients with attached vitreous body need a more intensive treatment monitoring compared to patients with detached vitreous body. Therefore, in eyes with initial posterior vitreous body detachment receiving a&#xa0;treat and extend regimen, the interval between anti-VEGF injections can be extended to 4&#xa0;instead of 2&#xa0;weeks without endangering the success of treatment.},
}
@article {pmid37815317,
year = {2024},
author = {Patel, SB and Heier, JS and Chaudhary, V and Wykoff, CC},
title = {Treatment of geographic atrophy: an update on data related to pegcetacoplan.},
journal = {Current opinion in ophthalmology},
volume = {35},
number = {1},
pages = {64-72},
doi = {10.1097/ICU.0000000000000845},
pmid = {37815317},
issn = {1531-7021},
mesh = {Humans ; *Geographic Atrophy/drug therapy/etiology ; *Macular Degeneration/drug therapy ; *Peptides, Cyclic ; Quality of Life ; Clinical Trials as Topic ; },
abstract = {PURPOSE OF REVIEW: Geographic atrophy is an advanced and currently untreatable form of age-related macular degeneration (AMD), which leads to significant compromise of visual function and quality of life. Dysregulation of the complement cascade has been directly implicated in AMD pathogenesis. Pegcetacoplan is a pegylated highly selective bicyclic peptide that inhibits the cleavage of complement component 3 (C3), which represents a key step in propagation of the complement cascade. The phase 2 FILLY trial as well as the phase 3 OAKS and DERBY trials have evaluated the safety and efficacy of pegcetacoplan for the treatment of GA.<br><br>RECENT FINDINGS: The FILLY, OAKS and DERBY trials have demonstrated that local inhibition of C3 cleavage with pegcetacoplan can reduce geographic atrophy lesion growth compared with sham with an effect size of approximately 11-35% depending on the specific trial and specific geographic atrophy phenotype considered. Overall pegcetacoplan has appeared to be well tolerated with the notable side effect of a dose-dependent increase in the rate of exudative AMD development in treated eyes.<br><br>SUMMARY: The FILLY, OAKS and DERBY trials have demonstrated that pegcetacoplan is a potentially viable treatment for geographic atrophy. Additional data from the 2-year outcomes of DERBY and OAKS as well as data from the ongoing 3-year GALE extension study will provide additional insights into the potential therapeutic benefit of pegcetacoplan. Future studies assessing complement inhibition at earlier stages of AMD, with the goal of preventing geographic atrophy formation, are warranted.},
}
@article {pmid37814173,
year = {2023},
author = {Kang, C},
title = {Avacincaptad Pegol: First Approval.},
journal = {Drugs},
volume = {83},
number = {15},
pages = {1447-1453},
pmid = {37814173},
issn = {1179-1950},
mesh = {Humans ; *Geographic Atrophy ; *Macular Degeneration/drug therapy ; Complement Inactivating Agents ; Complement C5 ; },
abstract = {Avacincaptad pegol (IZERVAY™; formerly Zimura[®]) is a complement C5 inhibitor that is being developed by IVERIC Bio, an Astellas company, for the treatment of geographic atrophy secondary to age-related macular degeneration. Avacincaptad pegol recently received approval for the treatment of adults with geographic atrophy secondary to age-related macular degeneration. This article summarizes the milestones in the development of avacincaptad pegol leading to this first approval for geographic atrophy secondary to age-related macular degeneration.},
}
@article {pmid37812861,
year = {2023},
author = {Peng, X and Zhang, T and Wu, Y and Wang, X and Liu, R and Jin, X},
title = {mPEG-CS-modified flexible liposomes-reinforced thermosensitive sol-gel reversible hydrogels for ocular delivery of multiple drugs with enhanced synergism.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {231},
number = {},
pages = {113560},
doi = {10.1016/j.colsurfb.2023.113560},
pmid = {37812861},
issn = {1873-4367},
mesh = {Humans ; *Liposomes ; Hydrogels/chemistry ; Polyethylene Glycols/chemistry ; Drug Delivery Systems ; *Chitosan/chemistry ; },
abstract = {Non-invasive drug delivery offers a safe treatment while improving patient compliance. However, due to the particular physiological structure of the ocular, long-term retention and sustained drug release of the drug delivery system is crucial. Herein, this study aimed to design mPEG-CS-modified flexible liposomes-reinforced thermosensitive sol-gel reversible hydrogels (mPEG-CS-FL-TSG) for the delivery of astragaloside IV (AS-IV) and tetramethylpyrazine (TMP) to treat age-related macular degeneration. In vitro biological properties of mPEG-CS-FL and mPEG-CS-FL-TSG showed that they could be successfully taken up by ARPE-19 cells, and the uptake rate of mPEG-CS-FL-TSG was higher. Not only that, the release rate of mPEG-CS-FL-TSG was slower. More significantly, the results showed that the cytotoxicity of mPEG-CS-FL-TSG was lower than that of mPEG-CS-FL. In vivo result revealed that the drug delivery system could prominently enhance the ocular bioavailability of AS-IV and TMP, which is the enhanced synergism of well-permeable liposome and slow-releasing hydrogel. In summary, the mPEG-CS-FL-TSG can compensate for the short retention time and sudden release of liposome, as well as the low drug penetration of hydrogel, in order to show great promise in the non-invasive delivery of multiple drugs for the treatment of posterior ocular diseases.},
}
@article {pmid37810589,
year = {2023},
author = {Hattenbach, LO and Abreu, F and Arrisi, P and Basu, K and Danzig, CJ and Guymer, R and Haskova, Z and Heier, JS and Kotecha, A and Liu, Y and Loewenstein, A and Seres, A and Willis, JR and Wykoff, CC and Paris, LP},
title = {BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion: Study Design and Rationale.},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100302},
pmid = {37810589},
issn = {2666-9145},
abstract = {PURPOSE: Dual inhibition of angiopoietin-2 and VEGF-A with faricimab (Vabysmo) offers excellent visual acuity gains with strong durability in patients with diabetic macular edema (ME) and neovascular age-related macular degeneration. The phase III BALATON/COMINO (NCT04740905/NCT04740931) trials will investigate the efficacy, safety, and durability of faricimab in patients with ME due to retinal vein occlusion (RVO).<br><br>DESIGN: Two identically designed global, randomized, double-masked, active comparator-controlled studies.<br><br>PARTICIPANTS: Anti-VEGF treatment-naive patients with branch, central, or hemiretinal RVO.<br><br>METHODS: Patients were randomized to 6 monthly injections of faricimab 6.0 mg or aflibercept 2.0 mg. From weeks 24 to 72, all patients received faricimab 6.0 mg administered in up to 16-week intervals using an automated treatment algorithm to generate a treat-and-extend-based personalized treatment interval dosing regimen. Personalized treatment interval adjustments were based on changes in central subfield thickness (CST) and best-corrected visual acuity (BCVA).<br><br>MAIN OUTCOME MEASURES: Primary end point was noninferiority of faricimab versus aflibercept in mean change from baseline in BCVA (week 24; noninferiority margin: 4 letters). Secondary end points (weeks 0-24) were mean change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire 25 composite score; proportion of patients gaining or avoiding loss of &#x2265; 15/&#x2265; 10/&#x2265; 5/> 0 letters. Secondary end points (weeks 24-72) were treatment durability (week 68); continuation of weeks 0 to 24 end points. Ocular/nonocular adverse events will be assessed.<br><br>RESULTS: In total, 1282 patients across 22 countries were enrolled (BALATON, 553 patients, 149 centers; COMINO, 729 patients, 193 centers).<br><br>CONCLUSIONS: Using a novel automated interval algorithm, BALATON/COMINO will evaluate the efficacy and safety of faricimab for ME secondary to RVO and provide key insights into how to personalize treatment.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37810255,
year = {2023},
author = {Wei-Zhang, S and Cui, B and Xing, M and Liu, J and Guo, Y and He, K and Bai, T and Dong, X and Lei, Y and Zhou, W and Zhou, H and Liu, S and Wang, X and Zhou, D and Yan, H},
title = {Chimpanzee adenovirus-mediated multiple gene therapy for age-related macular degeneration.},
journal = {iScience},
volume = {26},
number = {10},
pages = {107939},
pmid = {37810255},
issn = {2589-0042},
abstract = {Neovascular age-related macular degeneration AMD (nAMD) is characterized by choroidal neovascularization (CNV) and could lead to irreversible blindness. However, anti-vascular endothelial growth factor (VEGF) therapy has limited efficacy. Therefore, we generated a chimpanzee adenoviral vector (AdC68-PFC) containing three genes, pigment endothelial-derived factor (PEDF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble forms of CD59 (sCD59), to treat nAMD. The results showed that AdC68-PFC mediated a strong onset of PEDF, sFlt-1, and sCD59 expression both in vivo and in vitro. AdC68-PFC showed preventive and therapeutic effects following intravitreal (IVT) injection in the laser-induced CNV model and very low-density lipoprotein receptor-deficient (Vldlr[-/-]) mouse model. In vitro assessment indicated that AdC68-PFC had a strong inhibitory effect on endothelial cells. Importantly, the safety test showed no evidence of in vivo toxicity of adenovirus in murine eyes. Our findings suggest that AdC68-PFC may be a long-acting and safe gene therapy vector for future nAMD treatments.},
}
@article {pmid37810031,
year = {2023},
author = {Zhang, X and Du, S and Yang, D and Jin, X and Zhang, Y and Wang, D and Wang, H and Zhang, Y and Zhu, M},
title = {LncRNA MALAT1 knockdown inhibits the development of choroidal neovascularization.},
journal = {Heliyon},
volume = {9},
number = {9},
pages = {e19503},
pmid = {37810031},
issn = {2405-8440},
abstract = {In the pathogenesis of age-related macular degeneration, long non-coding RNAs have become important regulators. This study aimed to investigate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the progression of choroidal neovascularization (CNV) and the underlying mechanisms. The in vivo and in vitro model of CNV was established using laser-induced mouse CNV model and human choroidal vascular endothelial cells (HCVECs) exposed to hypoxia respectively. We explore the role of MALAT1 in the pathogenesis of CNV by using the small interference RNA both in vivo and in vitro. MALAT1 expression was found to be upregulated in the retinal pigment epithelial-choroidal complexes. MALAT1 knockdown inhibited CNV development and leakage in vivo and decreased HCVECs proliferation, migration, and tube formation in vitro. MALAT1 performed the task as a miR-17-5p sponge to regulate the expression of vascular endothelial growth factor A (VEGFA) and E26 transformation specific-1 (ETS1). This study provides a new perspective on the pathogenesis of CNV and suggests that the axis MALAT/miR-17-5p/VEGFA or ETS1 may be an effective therapeutic target for CNV.},
}
@article {pmid37809015,
year = {2023},
author = {Darooei, R and Nazari, M and Kafieh, R and Rabbani, H},
title = {Loss-Modified Transformer-Based U-Net for Accurate Segmentation of Fluids in Optical Coherence Tomography Images of Retinal Diseases.},
journal = {Journal of medical signals and sensors},
volume = {13},
number = {4},
pages = {253-260},
pmid = {37809015},
issn = {2228-7477},
abstract = {BACKGROUND: Optical coherence tomography (OCT) imaging significantly contributes to ophthalmology in the diagnosis of retinal disorders such as age-related macular degeneration and diabetic macular edema. Both diseases involve the abnormal accumulation of fluids, location, and volume, which is vitally informative in detecting the severity of the diseases. Automated and accurate fluid segmentation in OCT images could potentially improve the current clinical diagnosis. This becomes more important by considering the limitations of manual fluid segmentation as a time-consuming and subjective to error method.<br><br>METHODS: Deep learning techniques have been applied to various image processing tasks, and their performance has already been explored in the segmentation of fluids in OCTs. This article suggests a novel automated deep learning method utilizing the U-Net structure as the basis. The modifications consist of the application of transformers in the encoder path of the U-Net with the purpose of more concentrated feature extraction. Furthermore, a custom loss function is empirically tailored to efficiently incorporate proper loss functions to deal with the imbalance and noisy images. A weighted combination of Dice loss, focal Tversky loss, and weighted binary cross-entropy is employed.<br><br>RESULTS: Different metrics are calculated. The results show high accuracy (Dice coefficient of 95.52) and robustness of the proposed method in comparison to different methods after adding extra noise to the images (Dice coefficient of 92.79).<br><br>CONCLUSIONS: The segmentation of fluid regions in retinal OCT images is critical because it assists clinicians in diagnosing macular edema and executing therapeutic operations more quickly. This study suggests a deep learning framework and novel loss function for automated fluid segmentation of retinal OCT images with excellent accuracy and rapid convergence result.},
}
@article {pmid37808640,
year = {2023},
author = {Liu, J and Copland, DA and Clare, AJ and Gorski, M and Richards, BT and Scott, L and Theodoropoulou, S and Greferath, U and Cox, K and Bell, OH and Ou, K and Powell, JLB and Wu, J and Robles, LM and Li, Y and Nicholson, LB and Coffey, PJ and Fletcher, EL and Guymer, R and Radeke, MJ and Heid, IM and Hageman, GS and Chan, YK and Dick, AD},
title = {Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37808640},
issn = {2692-8205},
support = {R01 EY022310/EY/NEI NIH HHS/United States ; },
abstract = {Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD. IRAK-M expression in RPE declined with age or oxidative stress and was further reduced in AMD. IRAK-M-deficient mice exhibited increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M disrupted RPE cell homeostasis, including compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of AAV-expressing IRAK-M rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in IRAK-M-deficient mice. Our data support that replenishment of IRAK-M expression may redress dysregulated pro-inflammatory processes in AMD, thereby treating degeneration.},
}
@article {pmid37808513,
year = {2023},
author = {Takahashi, VKL and Balbino, M and Ruppert, ADP and de Carvalho, LS and Seixas, RCS},
title = {Lost to follow-up of patients who received intravitreal anti-vascular endothelial growth factor therapy to treat four different retina disorders in an individual center in Brazil.},
journal = {SAGE open medicine},
volume = {11},
number = {},
pages = {20503121231199655},
pmid = {37808513},
issn = {2050-3121},
abstract = {OBJECTIVES: To identify risk factors for loss to follow-up in periodic intravitreal anti-vascular endothelial growth factor injections for the treatment patients with diabetic macular edema, subretinal neovascularization, age-related macular degeneration, and retinal vein occlusion in a single eye center in São Paulo, Brazil.<br><br>METHODS: This was a retrospective longitudinal study that gathered information from 992 patients who required intravitreal anti-vascular endothelial growth factor drugs over 6&#x2009;months. The authors included age, eye disease, laterality, monthly income, distance, and payment mode as risk factors.<br><br>RESULTS: Two hundred and seventy patients (29.93%) were lost to follow-up. Multivariate analysis showed age, monthly income, eye involvement, and type of medical assistance independently associated with loss to follow-up. The odds of loss to follow-up were greater among older patients than those less than 50&#x2009;years (reference), p&#x2009;<&#x2009;0.001. The odds of loss to follow-up were greater among patients who received unilateral treatment than those who received bilateral injections (p&#x2009;=&#x2009;0.013). Concerning gross monthly income, there were no differences in the odds of the four salary strata; the data also indicate an absence of difference in the three strata of patients' distance to the clinic. Considering the diagnosis, only age-related macular degeneration showed greater odds of loss to follow-up (p&#x2009;=&#x2009;0.016). Finally, the data suggest greater odds of loss to follow-up in private patients than in those on a health care plan (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Loss to follow-up is paramount because many patients may remain unassisted concerning their eye diseases. Identifying the risk factors is crucial to enforcing measures to increase adherence and the long-term success of the treatment.},
}
@article {pmid37806362,
year = {2023},
author = {Kadri, MS and Singhania, RR and Anisha, GS and Gohil, N and Singh, V and Patel, AK and Patel, AK},
title = {Microalgal lutein: Advancements in production, extraction, market potential, and applications.},
journal = {Bioresource technology},
volume = {389},
number = {},
pages = {129808},
doi = {10.1016/j.biortech.2023.129808},
pmid = {37806362},
issn = {1873-2976},
mesh = {*Lutein ; *Microalgae/metabolism ; Biomass ; Dietary Supplements ; Phosphates/metabolism ; },
abstract = {Lutein, a bioactive xanthophyll, has recently attracted significant attention for numerous health benefits, e.g., protection of eye health, macular degeneration, and acute and chronic syndromes etc. Microalgae have emerged as the best platform for high-value lutein production with high productivity, lutein content, and scale-up potential. Algal lutein possesses numerous bioactivities, hence widely used in pharmaceuticals, nutraceuticals, aquaculture, cosmetics, etc. This review highlights advances in upstream lutein production enhancement and feasible downstream extraction and cell disruption techniques for a large-scale lutein biorefinery. Besides bioprocess-related advances, possible solutions for existing production challenges in microalgae-based lutein biorefinery, market potential, and emerging commercial scopes of lutein and its potential health applications are also discussed. The key enzymes involved in the lutein biosynthesizing Methyl-Erythritol-phosphate (MEP) pathway have been briefly described. This review provides a comprehensive updates on lutein research advancements covering scalable upstream and downstream production strategies and potential applications for researchers and industrialists.},
}
@article {pmid37806303,
year = {2023},
author = {Oncel, D and Oncel, D and Mishra, K and Oncel, M and Arevalo, JF},
title = {Current Management of Subretinal Hemorrhage in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {5-6},
pages = {295-305},
doi = {10.1159/000534440},
pmid = {37806303},
issn = {1423-0267},
mesh = {Humans ; *Tissue Plasminogen Activator/therapeutic use ; Retinal Hemorrhage/diagnosis/etiology/therapy ; Retina ; *Macular Degeneration/complications/diagnosis/therapy ; Vitrectomy/methods ; Intravitreal Injections ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Fibrinolytic Agents/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among individuals aged 65 years and older in the USA. For individuals diagnosed with AMD, approximately 12% experience varying levels of subretinal hemorrhage (SRH), which can be further classified by size into small, medium, and massive measured in disc diameters. SRH is an acute and rare sight-threatening complication characterized by an accumulation of blood under the retina arising from the choroidal or retinal circulation. Released iron toxins, reduced nutrient supply, fibrin meshwork contraction, and outer retinal shear forces created by SRH contribute to visual loss, macular scarring, and photoreceptor damage. SRH treatment strategies aim to displace hemorrhage from the foveal region and prevent further bleeding. Although there are no standardized treatment protocols for SRH, several surgical and nonsurgical therapeutical approaches may be employed. The most common surgical approaches that have been utilized are pars plana vitrectomy (PPV) combined with multiple maneuvers such as the removal of choroidal neovascularization lesions, macular translocation, retinal pigment epithelium patch repair, SRH drainage, intravitreal injection of recombinant-tissue plasminogen activator (tPA), expansile gas and air displacement, and anti-vascular endothelial growth factor (anti-VEGF) injections. Nonsurgical therapeutical approaches include intravitreal anti-VEGF monotherapy, intravitreal tPA administration without PPV, and photodynamic therapy. This review article aims to explore the current treatment strategies and supporting literature regarding both surgical and nonsurgical, of SRH in patients with AMD. Moreover, this article also aims to highlight the distinct treatment modalities corresponding to different sizes of SRH.},
}
@article {pmid37803306,
year = {2023},
author = {Xu, N and Sun, T and Wang, Y and Tong, X and Lu, S and Yang, F and Wang, J and Bo, Q and Sun, J and Sun, X},
title = {Dynamic changes in macrophage morphology during the progression of choroidal neovascularization in a laser-induced choroidal neovascularization mouse model.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {401},
pmid = {37803306},
issn = {1471-2415},
support = {2021JC003//Shanghai eye hospital in-hospital foundation/ ; SHDC2020CR2040B, SHDC2020CR5014, SHDC12020111//Shanghai Hospital Development Center/ ; SHDC2020CR2040B, SHDC2020CR5014, SHDC12020111//Shanghai Hospital Development Center/ ; ZY(2021-2023)-0207-01//A three-year action plan for TCM inheritance, innovation and development/ ; 82171076//National Natural Science Foundation of China/ ; TM202115PT//Shanghai Collaborative Innovation Center for Translational Medicine/ ; },
mesh = {Humans ; Mice ; Animals ; *Choroidal Neovascularization/etiology/metabolism ; Macrophages/metabolism/pathology ; Choroid/pathology ; Lasers ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {BACKGROUND: Neovascular age-related macular degeneration (AMD) is responsible for the majority of severe vision loss cases and is mainly caused by choroidal neovascularization (CNV). This condition persists or recurs in a subset of patients and regresses after 5 or more years of anti-vascular endothelial growth factor (VEGF) treatment. The precise mechanisms of CNV continue to be elucidated. According to our previous studies, macrophages play a critical role in CNV. Herein, we aimed to determine the morphological changes in macrophages in CNV to help us understand the dynamic changes.<br><br>METHODS: Mice were subjected to laser injury to induce CNV, and lesion expansion and macrophage transformation were examined by immunofluorescence and confocal analysis. Several strategies were used to verify the dynamic changes in macrophages. Immunofluorescence and confocal assays were performed on choroidal flat mounts to evaluate the morphology and phenotype of macrophages in different CNV phases, and the results were further verified by western blotting and RT-PCR.<br><br>RESULTS: The location of infiltrated macrophages changed after laser injury in the CNV mouse model, and macrophage morphology also dynamically changed. Branching macrophages gradually shifted to become round with the progression of CNV, which was certified to be an M2 phenotypic shift.<br><br>CONCLUSIONS: Dynamic changes in macrophage morphology were observed during CNV formation, and the round-shaped M2 phenotype could promote neovascularization. In general, the changes in morphology we observed in this study can help us to understand the critical role of macrophages in CNV progression and exploit a potential treatment option for CNV indicated by a shift in macrophage polarity.},
}
@article {pmid37803144,
year = {2024},
author = {Cheung, CMG},
title = {Macular neovascularization and polypoidal choroidal vasculopathy: phenotypic variations, pathogenic mechanisms and implications in management.},
journal = {Eye (London, England)},
volume = {38},
number = {4},
pages = {659-667},
pmid = {37803144},
issn = {1476-5454},
support = {NMRC/LCG/004/2018//MOH | National Medical Research Council (NMRC)/ ; },
mesh = {Humans ; *Choroidal Neovascularization/diagnosis/drug therapy/etiology ; Polypoidal Choroidal Vasculopathy ; Angiogenesis Inhibitors/therapeutic use ; Fluorescein Angiography/methods ; Vascular Endothelial Growth Factor A/therapeutic use ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Choroid/pathology ; Biological Variation, Population ; Tomography, Optical Coherence/methods ; *Polyps/diagnosis/drug therapy/complications ; Retrospective Studies ; Indocyanine Green ; },
abstract = {Advances in imaging have led to improved ability to characterize variations in clinical sub-phenotypes of macular neovascularization (MNV) in Age-related macular degeneration (AMD). Polypoidal choroidal vasculopathy (PCV) was initially described based on characteristic features observed in indocyanine green angiography (ICGA) and was thought to be a distinct entity from AMD. However, subsequent careful observations based on confocal scanning laser ophthalmoscopy-based ICGA, optical coherence tomography (OCT) and OCT angiography have led researchers to appreciate similarities between PCV lesion and type 1 MNV in typical neovascular AMD. Concurrently, clinical trials have shown that anti-VEGF monotherapy can achieve favourable visual outcome in the majority of eyes with PCV. These learnings have led to a shift in the way PCV is managed over the past decade. Recent studies have supported the use of non-ICGA based imaging modality to screen for PCV and the adoption of anti-VEGF monotherapy as initial therapy for PCV. A focus of recent research has been in the understanding of the role of choroidal alterations in the pathogenesis of PCV. The concept of pachychoroid in leading to outer retinal ischemia has garnered increasing support. Future research in this area should evaluate the potential of choroidal morphology in guiding personalized therapy in PCV.},
}
@article {pmid37801159,
year = {2023},
author = {Boneva, S and Haritoglou, C and Schultheiss, M and Binder, S and Sebag, J},
title = {[Role of vitreous in the pathogenesis of neovascular age-related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {120},
number = {10},
pages = {992-998},
pmid = {37801159},
issn = {2731-7218},
mesh = {Humans ; Vitreous Body/surgery ; Vascular Endothelial Growth Factor A ; *Vitreous Detachment/complications ; *Macular Degeneration/complications ; *Retinal Diseases/complications ; },
abstract = {Age-related changes in vitreous molecular and anatomic morphology begin early in life and involve two major processes: vitreous liquefaction and weakening of vitreo-retinal adhesion. An imbalance in these two processes results in anomalous posterior vitreous detachment (PVD), which comprises, among other conditions, vitreo-macular adhesion (VMA) and traction (VMT). VMA is more common in patients with neovascular age-related macular degeneration (nAMD) than age-matched control patients, with the site of posterior vitreous adherence to the inner retina correlating with location of neovascular complexes. The pernicious effects of an attached posterior vitreous on age-related macular degeneration (AMD) progression involve mechanical forces, enhanced fluid influx and inflammation in and between the retinal layers, hypoxia leading to an accumulation of vascular endothelial growth factor (VEGF) and other stimulatory cytokines, and probably an infiltration of hyalocytes. It has been shown that vitrectomy not only mitigates progression to end-stage AMD, but existing choroidal neovascularization regresses after surgery. Thus, surgical PVD induction during vitrectomy or by pharmacologic vitreolysis may be considered in non-responders to anti-VEGF treatment with concomitant VMA.},
}
@article {pmid37800778,
year = {2023},
author = {Jirarattanasopa, P and Khongsakdinasarn, N and Ratanasukon, M and Bhurayanontachai, P and Dangboon Tsutsumi, W},
title = {Visual outcomes of early and late vitrectomy for breakthrough vitreous hemorrhage associated with exudative age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {Medicine},
volume = {102},
number = {40},
pages = {e35364},
pmid = {37800778},
issn = {1536-5964},
mesh = {Humans ; *Vitreous Hemorrhage/surgery/complications ; Polypoidal Choroidal Vasculopathy ; Vitrectomy ; Retrospective Studies ; *Macular Degeneration/complications/surgery/drug therapy ; Fluorescein Angiography ; Tomography, Optical Coherence ; Intravitreal Injections ; },
abstract = {To compare the visual outcomes of early and late vitrectomy for breakthrough vitreous hemorrhage (VH) associated with exudative age-related macular degeneration (exudative AMD) and polypoidal choroidal vasculopathy (PCV). A retrospective chart review was performed with data of all patients diagnosed with exudative AMD and PCV-related breakthrough VH who underwent early or late vitrectomy (within or after 3 months, respectively). Demographic data and best-corrected visual acuity (BCVA) at baseline, and 1, 3, 6, and 12 months postoperatively were recorded and analyzed. Overall, 105 eyes with breakthrough VH were examined and categorized in either the early or late vitrectomy group. In the early and late vitrectomy group, LogMAR BCVA improved from 2.15 ± 0.08 and 2.07 ± 0.14 at baseline to 1.26 ± 0.09 and 1.27 ± 0.14 at 12 months, respectively (P < .001). Between early and late vitrectomy, the PCV subgroup demonstrated improved LogMAR BCVA at 1 year, but there was no statistically significant (P = .754). Conversely, the LogMAR BCVA improvement at 1 year in the early vitrectomy group demonstrated statistically significant differences from the late vitrectomy group (P = .025) in the exudative AMD subgroup. Both, early and late vitrectomy can improve visual acuity in patients with breakthrough VH secondary to exudative AMD and PCV. However, early vitrectomy is more beneficial for breakthrough VH-associated exudative AMD.},
}
@article {pmid37800611,
year = {2024},
author = {Vinge, E and Bro, T},
title = {Treatment burden on patients receiving intravitreal anti-VEGF for wet age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {4},
pages = {478-482},
doi = {10.1111/aos.15783},
pmid = {37800611},
issn = {1755-3768},
support = {2021-00024//Edwin Jordans Stiftelse f&#xf6;r Oftalmologisk Forskning/ ; //Futurum - Akademin f&#xf6;r H&#xe4;lsa och V&#xe5;rd, Region J&#xf6;nk&#xf6;pings l&#xe4;ns/ ; },
mesh = {Aged ; Female ; Humans ; Male ; *Angiogenesis Inhibitors/administration &amp; dosage ; Bevacizumab/administration &amp; dosage ; Caregivers ; Cost of Illness ; Follow-Up Studies ; *Intravitreal Injections ; Ranibizumab/administration &amp; dosage ; Surveys and Questionnaires ; Sweden/epidemiology ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; *Wet Macular Degeneration/drug therapy/diagnosis ; },
abstract = {PURPOSE: The aim of this study was to map the treatment burden for patients with wet age-related macular degeneration (wAMD).<br><br>METHOD: Patients with ongoing treatment with anti-VEGF for wAMD at a Swedish eye unit underwent a survey about the time spent receiving treatment, caregiver assistance, way of transportation, self-rated vision and negative experiences associated with the treatment such as discomfort, anxiety or transportation problems. Information about current visual acuity, number of treatments and current treatment intervals were obtained from medical records.<br><br>RESULTS: The study included 93 patients with an average age of 79.9&#x2009;years, 68% were women. The average interval between treatments was 7.3&#x2009;weeks, and 26% had active treatment in both eyes. On average, patients had to spend 2.7&#x2009;h (2.4-2.9: 95% CI) per treatment and a caregiver assisted the patient in 58% of cases. Caregivers spent on average 2.6&#x2009;h (2.5-2.8: 95% CI) per visit, and 19% needed to take time off work. The majority (91%) of patients did not experience any transportation problems associated with treatment. A multivariate logistic regression analysis showed a significantly lower odds ratio for discomfort with higher self-rated vision and a significantly higher odds ratio for discomfort with longer treatment intervals.<br><br>DISCUSSION: Anti-VEGF treatment is an effective treatment for wAMD. However, the relatively short treatment intervals place a considerable burden on patients and their relatives regarding time. Although the patients in this study had to spend a lot of time to receive treatment, the majority did not experience any problems associated with treatment.},
}
@article {pmid37797661,
year = {2023},
author = {Zhang, W and He, Y and Zhang, Y},
title = {CircRNA in ocular neovascular diseases: Fundamental mechanism and clinical potential.},
journal = {Pharmacological research},
volume = {197},
number = {},
pages = {106946},
doi = {10.1016/j.phrs.2023.106946},
pmid = {37797661},
issn = {1096-1186},
mesh = {Humans ; Infant, Newborn ; RNA, Circular/genetics ; Eye ; *Retinal Diseases ; *Macular Degeneration ; *Diabetic Retinopathy/genetics ; },
abstract = {Ocular neovascular disease (OND), characterized by the aberrant formation of immature blood vessels, is the leading cause of vision impairment and blindness. It is important to find effective ways to diagnose and treat these diseases. Circular RNA (circRNA) is a group of endogenous non-coding RNA that play a crucial role in regulating different biological processes. Due to their close association with ocular disease and angiogenesis, circRNAs have become a hotspot in OND research. In this review, we intensively investigate the possibility of using circRNAs in the management of ONDs. In general, angiogenesis is divided into five phases. On the basis of these five steps, we describe the potential of using circRNAs by introducing how they regulate angiogenesis. Subsequently, the interactions between circRNAs and ONDs, including pterygium, corneal neovascularization, age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, are analyzed in detail. We also introduce the potential use of circRNAs as OND diagnostic biomarkers. Finally, we summarize the prospects of using circRNAs as a potential strategy in OND management. The gaps in recent research are also pointed out with the purpose of promoting the introduction of circRNAs into clinical applications.},
}
@article {pmid37797226,
year = {2023},
author = {Hirani, K and Bansinath, M and Mittal, R and Lemos, JRN and Adis, E and Poojari, P and Igoe, JM and Soares, MR and Bhattacharya, S and Weiss, RE},
title = {Eyes on the Prize: Decoding the Ophthalmic Product Regulations and Intricacies of the U.S. Food and Drug Administration Approval.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {39},
number = {8},
pages = {572-582},
doi = {10.1089/jop.2023.0071},
pmid = {37797226},
issn = {1557-7732},
mesh = {United States ; Humans ; United States Food and Drug Administration ; Drug Approval ; Pharmaceutical Preparations ; *Biological Products ; *Awards and Prizes ; },
abstract = {The dynamic and continuously evolving field of ophthalmology necessitates rigorous regulatory oversight in the United States. This review outlines the multifaceted Food and Drug Administration's (FDA) approval process for ophthalmic products, detailing the classifications, pathways, and regulatory compliance for devices, drugs, biologics, and combination products. Particular emphasis is placed on distinct frameworks for Class I, II, and III devices, as well as regulations for drugs, biologics, and combination products. The organizational structure of the FDA is detailed, with highlights on specific Ophthalmology oversight divisions, historical regulatory evolution, and initiatives such as Patient-Focused Drug Development. An in-depth examination of the regulatory journey, ranging from initial research to post-marketing surveillance, includes practical guidance through stages such as Pre-Investigational New Drug/Pre-Submission consultations, clinical trials, new drug application/biologics license application/premarket approval submissions, and FDA advisory committee interactions. The article underscores the importance of early interactions with the health authorities, interdisciplinary team collaboration, adherence to current standards, and the anticipation of policy changes to ensure patient safety. It concludes with an analysis of 4 key FDA-approved ophthalmic products, including Eylea[®], Luxturna[®], Alphagan P[®], and the Raindrop[®] Near Vision Inlay, detailing their contributions to ophthalmic care and offering valuable insights into their respective clinical trials, regulatory pathways, and potential implications. These case studies are included to illustrate both successful and failed ophthalmic product launches, thereby highlighting the importance of alignment with regulatory compliance.},
}
@article {pmid37796711,
year = {2023},
author = {Wichrowska, M and Goździewska, E and Kocięcki, J},
title = {The Safety of Anti-VEGF Treatment, in the Context of the Retinal Nerve Fibre Layer, in Patients with Wet Age-Related Macular Degeneration: A Review.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {28},
number = {9},
pages = {222},
doi = {10.31083/j.fbl2809222},
pmid = {37796711},
issn = {2768-6698},
mesh = {Humans ; Angiogenesis Inhibitors/adverse effects ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy ; Nerve Fibers ; Ranibizumab/pharmacology/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/pharmacology/therapeutic use ; Retrospective Studies ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Wet Macular Degeneration/drug therapy ; },
abstract = {Anti-vascular endothelial growth factor (VEGF) drugs are widely used in modern ophthalmology, especially in treating macular disorders like age-related macular degeneration or diabetic macular edema. Protocols for such treatments include repeated administration of intravitreal injections, with the volume of drug injected into the vitreous chamber seemingly high enough to cause an increase in intraocular pressure. Hence, questions might arise if such therapeutic approaches are safe for ocular tissue. Moreover, anti-VEGF compounds may theoretically harm the retinal nerve fibers due to the inhibition of VEGF and its neuroprotective effects. Thus, this manuscript aims to review the literature regarding studies evaluating the retinal nerve fiber layer (RNFL) in eyes receiving anti-VEGF treatment due to age-related macular degeneration. The RNFL was chosen as a subject of this review, as it is the innermost retinal layer exposed to the direct action of intravitreally administered drugs. The results of the available studies remain inconclusive. Most researchers seem to confirm the safety of the anti-VEGF treatment in wet age-related macular degeneration, at least regarding the retinal nerve fiber layer. However, some authors noticed that the influence of anti-VEGFs on RNFL could become apparent after more than thirty injections. Nonetheless, the authors of all studies agree that further, long-term observations are needed to help clinicians understand the effect of anti-VEGF treatment on the dynamics of changes in the thickness of retinal nerve fibers in patients with the wet form of age-related macular degeneration.},
}
@article {pmid37796497,
year = {2023},
author = {Dessouki, A and He, L and Park, K and Chen, H and Chow, CC},
title = {Presumed Silicone Oil Droplets After Intravitreal Pegcetacoplan Injections.},
journal = {JAMA ophthalmology},
volume = {141},
number = {11},
pages = {1062-1065},
pmid = {37796497},
issn = {2168-6173},
mesh = {*Eye Diseases/chemically induced ; *Geographic Atrophy/chemically induced ; Retrospective Studies ; Intravitreal Injections ; Vision Disorders ; Aged, 80 and over ; Retina ; Silicone Oils/adverse effects ; Female ; Humans ; Silicones ; },
abstract = {IMPORTANCE: Recently, intravitreal pegcetacoplan became the first drug to gain US Food and Drug Administration approval for the treatment of geographic atrophy associated with nonexudative age-related macular degeneration, but the administration of this medication may be associated with unanticipated posttreatment complications.<br><br>OBJECTIVE: To assess the prevalence of presumed silicone oil droplets in the vitreous cavity after intravitreal injection of pegcetacoplan.<br><br>This case series study involved a retrospective record review of all 55 patients treated with intravitreal pegcetacoplan, 0.1 mL in 150-mg/mL solution, between March 24 and June 5, 2023, at a single specialty retina practice. All injections were done using needles from the kit supplied by Apellis Pharmaceuticals on a 1-mL McKesson Luer lock syringe.<br><br>MAIN OUTCOMES AND MEASURES: The presence or absence of presumed silicone bubbles detected during dilated biomicroscopic fundus examination and/or on color fundus photographs, the presence or absence of symptoms, change in visual acuity, and/or increase in intraocular pressure.<br><br>RESULTS: A total of 62 intravitreal pegcetacoplan injections were given to 55 patients (mean [SD] age, 83.8 [7.8] years; 33 women [60%]) from March 24 to June 5, 2023. Of the 55 patients, 16 (29%; mean [SD] age, 83.8 [7.4] years; 9 women [56%]) had presumed intravitreal silicone droplets discovered 2 to 4 weeks after treatment, 3 of which were documented on color fundus photographs. Of the 16 patients, 14 (88%) were symptomatic for new floaters that they described as persistent, while 2 (13%) were asymptomatic. There were no signs of inflammation or infection, no increases in intraocular pressure, and no changes in visual acuity for all 16 patients.<br><br>CONCLUSIONS AND RELEVANCE: A substantial percentage of patients had symptomatic floaters from presumed intravitreal silicone oil droplets after injections of pegcetacoplan using a McKesson 1-mL Luer lock syringe. These findings support consideration of informing patients of this potential adverse effect, avoiding use of the McKesson syringe, and considering use of silicone-free syringes for pegcetacoplan injections.},
}
@article {pmid37796039,
year = {2023},
author = {Das, N and Chaurasia, S and Singh, RP},
title = {A review of emerging tyrosine kinase inhibitors as durable treatment of neovascular age-related macular degeneration.},
journal = {Expert opinion on emerging drugs},
volume = {28},
number = {3},
pages = {203-211},
doi = {10.1080/14728214.2023.2259790},
pmid = {37796039},
issn = {1744-7623},
mesh = {Humans ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Tyrosine Kinase Inhibitors/therapeutic use ; },
abstract = {INTRODUCTION: Current treatment for age-related macular degeneration poses a large burden on patients and the inability of patients to adhere to this immense burden can lead to worse visual outcomes. Novel treatments have been proposed to extend treatment intervals and reduce visit burden.<br><br>AREAS COVERED: This review article summarizes phase I and phase II clinical trials of tyrosine kinase inhibitors as durable treatment options for patient with neovascular age-related macular degeneration.<br><br>EXPERT OPINION: Tyrosine kinase inhibitors have shown substantial promise in reducing treatment burden while maintaining visual acuity and anatomic outcomes with favorable safety profiles. Several platforms have shown positive outcomes in initial trials and are currently moving toward phase III clinical trials.},
}
@article {pmid37795187,
year = {2023},
author = {Verghese, P},
title = {The utility of peripheral stereopsis.},
journal = {Frontiers in neuroscience},
volume = {17},
number = {},
pages = {1217993},
pmid = {37795187},
issn = {1662-4548},
support = {R01 EY027390/EY/NEI NIH HHS/United States ; R01 EY034370/EY/NEI NIH HHS/United States ; },
abstract = {This perspective article makes the case for evaluating and training peripheral stereopsis, particularly when the central visual field is compromised in one or both eyes. Examples of clinical conditions that preferentially affect the central visual field include macular degeneration, which affects the central macular region in one or both eyes, and amblyopia where the central field is often affected in one eye, but the peripheral field is largely intact. While binocular acuity may be preserved when the monocular central field of one eye is affected, fine stereopsis is compromised because it requires intact vision in corresponding locations in the two eyes. Even in these clinical conditions, recent studies that map stereoacuity at locations across the visual field demonstrate that the periphery supports coarse stereopsis, and that training efforts to use residual stereopsis may have greater benefit if they take this finding into account.},
}
@article {pmid37794584,
year = {2023},
author = {Lee, Q and Chan, WC and Qu, X and Sun, Y and Abdelkarim, H and Le, J and Saqib, U and Sun, MY and Kruse, K and Banerjee, A and Hitchinson, B and Geyer, M and Huang, F and Guaiquil, V and Mutso, AA and Sanders, M and Rosenblatt, MI and Maienschein-Cline, M and Lawrence, MS and Gaponenko, V and Malik, AB and Komarova, YA},
title = {End binding-3 inhibitor activates regenerative program in age-related macular degeneration.},
journal = {Cell reports. Medicine},
volume = {4},
number = {10},
pages = {101223},
pmid = {37794584},
issn = {2666-3791},
support = {R01 HL103922/HL/NHLBI NIH HHS/United States ; HHSN268201700007C/HL/NHLBI NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; R01 HL045638/HL/NHLBI NIH HHS/United States ; },
mesh = {Mice ; Animals ; Endothelial Cells/metabolism ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; *Wet Macular Degeneration/drug therapy/metabolism ; },
abstract = {Wet age-related macular degeneration (AMD), characterized by leaky neovessels emanating from the choroid, is a main cause of blindness. As current treatments for wet AMD require regular intravitreal injections of anti-vascular endothelial growth factor (VEGF) biologics, there is a need for the development of less invasive treatments. Here, we designed an allosteric inhibitor of end binding-3 (EB3) protein, termed EBIN, which reduces the effects of environmental stresses on endothelial cells by limiting pathological calcium signaling. Delivery of EBIN via eye drops in mouse and non-human primate (NHP) models of wet AMD prevents both neovascular leakage and choroidal neovascularization. EBIN reverses the epigenetic changes induced by environmental stresses, allowing an activation of a regenerative program within metabolic-active endothelial cells comprising choroidal neovascularization (CNV) lesions. These results suggest the therapeutic potential of EBIN in preventing the degenerative processes underlying wet AMD.},
}
@article {pmid37794027,
year = {2023},
author = {Luttrull, JK and Gray, G and Bhavan, SV},
title = {Vision protection therapy for prevention of neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {16710},
pmid = {37794027},
issn = {2045-2322},
mesh = {Humans ; *Wet Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Visual Acuity ; Retina ; *Geographic Atrophy/drug therapy ; },
abstract = {To access the effect of vision protection therapy on neovascular conversion in age-related macular degeneration (AMD). Patient unidentified data aggregated by Vestrum Health, LLC (VH) from over 320 US retina specialists was analyzed to compare the conversion rate from dry to neovascular (wet) AMD in a practice employing VPT (VPT group) compared to those employing standard care alone (SCA group) between January 2017 through July 2023. 500,00 eyes were filtered then matched for neovascular conversion risk factors by propensity scoring and compared in a 10/1 ratio of 7370 SCA and 737 VPT treated eyes. SCA eyes had significantly fewer clinical encounters and shorter follow up than the VPT group. Despite this, the risk of neovascular conversion by PS was significantly lower in the VPT group compared to SCA (HR 5.73, p < 0.0001). Analysis matching the encounter frequency of both groups as a post-randomization variable produced a similar HR (HR 5.98, p < 0.0001). Because 9% of eyes in the VPT group were not treated with VPT due to bilateral early (low-risk) AMD, analysis comparing the SCA group to VPT-treated eyes was done that also showed significantly lower conversion rates in the VPT-treated eyes, with or without encounter frequency matching (HR 5.84, 5.65, p < 0.0001). Visual acuity was consistently better in VPT eyes compared to SCA eyes throughout the study time window. The advantage of VPT over SCA increased with increased SCA encounter frequency and higher conversion risk factors, including age and ICD10 coded dry AMD severity. Neovascular (wet) AMD is the main cause of irreversible visual loss worldwide. Consistent with two prior studies, the current study finds Vision Protection Therapy markedly more effective at both recognizing and preventing neovascular AMD than the current standard of care, benefiting the highest risk dry AMD eyes the most.},
}
@article {pmid37793105,
year = {2023},
author = {Stanford, P},
title = {Age-related macular degeneration: care of the patient in the community setting.},
journal = {British journal of community nursing},
volume = {28},
number = {10},
pages = {498-502},
doi = {10.12968/bjcn.2023.28.10.498},
pmid = {37793105},
issn = {1462-4753},
mesh = {Humans ; *Macular Degeneration/therapy/diagnosis ; },
abstract = {The aim of this article is to explain age-related macular degeneration (AMD) and how it impacts on the wellbeing of patients in the community setting. It explores the anatomy and physiology associated with AMD, its symptoms and treatment, and goes on to discuss related nursing care.},
}
@article {pmid37792693,
year = {2023},
author = {Williamson, RC and Selvam, A and Sant, V and Patel, M and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Chhablani, J},
title = {Radiomics-Based Prediction of Anti-VEGF Treatment Response in Neovascular Age-Related Macular Degeneration With Pigment Epithelial Detachment.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {10},
pages = {3},
pmid = {37792693},
issn = {2164-2591},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Pilot Projects ; Retrospective Studies ; *Retinal Detachment/diagnostic imaging/drug therapy/complications ; *Macular Degeneration/diagnostic imaging/drug therapy ; },
abstract = {PURPOSE: Machine learning models based on radiomic feature extraction from clinical imaging data provide effective and interpretable means for clinical decision making. This pilot study evaluated whether radiomics features in baseline optical coherence tomography (OCT) images of eyes with pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (nAMD) can predict treatment response to as-needed anti-vascular endothelial growth factor (VEGF) therapy.<br><br>METHODS: Thirty-nine eyes of patients with PED undergoing anti-VEGF therapy were included. All eyes underwent a loading dose followed by as-needed therapy. OCT images at baseline, month 3, and month 6 were analyzed. Images were manually separated into non-responding, recurring, and responding eyes based on the presence or absence of subretinal fluid at month 6. PED radiomics features were then extracted from each image and images were classified as responding or recurring using a machine learning classifier applied to the radiomics features.<br><br>RESULTS: Linear discriminant analysis classification of baseline features as responsive versus recurring resulted in classification performance of 64.0% (95% confidence interval [CI] = 0.63-0.65), area under the curve (AUC = 0.78, 95% CI = 0.72-0.82), sensitivity 0.79 (95% CI = 0.63-0.87), and specificity 0.58 (95% CI = 0.50-0.67). Further analysis of features in recurring eyes identified a significant shift toward non-responding mean feature values over 6 months.<br><br>CONCLUSIONS: Our results demonstrate the use of radiomics features as predictors for treatment response to as-needed anti-VEGF therapy. Our study demonstrates the potential for radiomics feature in clinical decision support for personalizing anti-VEGF therapy.<br><br>TRANSLATIONAL RELEVANCE: The ability to use PED texture features to predict treatment response facilitates personalized clinical decision making.},
}
@article {pmid37791838,
year = {2024},
author = {Akbulut, E and Kirik, F and Ekinci Aslanoglu, C and Hekimoglu, ER and Haciosmanoglu Aldogan, E and Ozdemir, MH},
title = {The Inflammatory and Cytological Effect of Repeated Povidone-Iodine Application in Patients Receiving Intravitreal Injections.},
journal = {Eye &amp; contact lens},
volume = {50},
number = {2},
pages = {73-78},
doi = {10.1097/ICL.0000000000001044},
pmid = {37791838},
issn = {1542-233X},
support = {20210217//Bezmialem Vak&#xc4;&#xb1;f &#xc3;&#x153;niversitesi/ ; },
mesh = {Humans ; *Povidone-Iodine ; Intravitreal Injections ; Prospective Studies ; *Interleukin-6/metabolism ; Conjunctiva/pathology ; Tears/metabolism ; },
abstract = {OBJECTIVE: To investigate the effect of repeated povidone-iodine (PVI) application on the ocular surface parameters of patients who received intravitreal injections.<br><br>MATERIALS AND METHODS: In this prospective study, 52 eyes of 52 patients with age-related macular degeneration who underwent unilateral intravitreal injection at least three times in the last 1 year (intravitreal injection [IVI] group), 52 fellow eyes with no previous intravitreal injection (NIVI group), and 51 eyes of 51 healthy subjects (control) were included. Tear break-up time (TBUT), the Schirmer test, the Oxford staining score, the Ocular Surface Disease Index questionnaire, conjunctival impression cytology, and tear inflammatory cytokine levels (interleukin [IL]-1&#x3b2; and IL-6) were analyzed in all participants.<br><br>RESULTS: The IVI group had lower TBUT and higher Oxford staining score than the NIVI and control groups (P <0.05). No significant difference was found between the groups in the Schirmer test (P =0.161). Conjunctival impression cytology analysis revealed that the IVI group had a significantly lower goblet cell count and significantly higher Nelson staging result than the NIVI and control groups (P <0.05). As a result of tear cytokine analysis, although IVI and NIVI groups had higher IL-1&#x3b2; and IL-6 levels than the control group (P <0.05), there was no difference between NIVI and IVI groups (P &#x2265;0.05).<br><br>CONCLUSIONS: Repeated PVI application caused cytotoxic injury to the ocular surface, resulting in goblet cell loss and squamous metaplasia of epithelial cells. As a result, the stability of the tear film layer was found to be impaired and ocular surface-related symptoms developed in patients.},
}
@article {pmid37791280,
year = {2023},
author = {Rosenfeld, PJ and Cheng, Y and Shen, M and Gregori, G and Wang, RK},
title = {Unleashing the power of optical attenuation coefficients to facilitate segmentation strategies in OCT imaging of age-related macular degeneration: perspective.},
journal = {Biomedical optics express},
volume = {14},
number = {9},
pages = {4947-4963},
pmid = {37791280},
issn = {2156-7085},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; },
abstract = {The use of optical attenuation coefficients (OAC) in optical coherence tomography (OCT) imaging of the retina has improved the segmentation of anatomic layers compared with traditional intensity-based algorithms. Optical attenuation correction has improved our ability to measure the choroidal thickness and choroidal vascularity index using dense volume scans. Algorithms that combine conventional intensity-based segmentation with depth-resolved OAC OCT imaging have been used to detect elevations of the retinal pigment epithelium (RPE) due to drusen and basal laminar deposits, the location of hyperpigmentation within the retina and along the RPE, the identification of macular atrophy, the thickness of the outer retinal (photoreceptor) layer, and the presence of calcified drusen. OAC OCT algorithms can identify the risk-factors that predict disease progression in age-related macular degeneration.},
}
@article {pmid37790350,
year = {2023},
author = {Künzel, SH and Broadbent, E and Möller, PT and Lindner, M and Goerdt, L and Czauderna, J and Schmitz-Valckenberg, S and Holz, FG and Pfau, M and Fleckenstein, M},
title = {Impact of lesion location and functional parameters on vision-related quality of life in geographic atrophy secondary to AMD.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {37790350},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY033365/EY/NEI NIH HHS/United States ; R01 EY034965/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND/AIMS: The primary objective was to determine how structural and functional parameters influence the vision-related quality of life (VRQoL) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>METHODS: This prospective, non-interventional, natural-history 'Directional Spread in Geographic-Atrophy' study was conducted at the University Eye Hospital in Bonn, enrolling 82 patients with bilateral GA. Parameters such as GA location (assessed by the Early Treatment Diabetic Retinopathy Study grid), best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), reading acuity, and speed were examined. The association between these parameters and VRQoL, as gauged using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25), was analyzed through least absolute shrinkage and selection operator with linear mixed-effects models.<br><br>RESULTS: The average total GA area observed was 2.9 &#xb1; 1.2 mm[2] (better eye) and 3.1 &#xb1; 1.3 mm[2] (worse eye). The VRQoL scores for distance and near activities were most associated with the inner lower and inner left subfields of the better eye. For foveal-sparing patients, the LLVA of the better eye was the predominant determinate impacting all VRQoL scales.<br><br>CONCLUSION: GA location, specifically the inner lower and inner left subfields of the better eye, has a notable effect on VRQoL in GA patients. LLVA stands out as especially vital in foveal-sparing patients, underscoring the importance for clinicians to incorporate considerations of GA location and functional parameters into their risk-benefit assessments for emerging treatments.},
}
@article {pmid37790320,
year = {2023},
author = {Sadda, S and Verma, A and Corradetti, G and Nittala, M and He, Y and Nassisi, M and Velaga, SB and Haines, J and Pericak-Vance, M and Stambolian, D},
title = {Longitudinal evaluation of the distribution of intraretinal hyper-reflective foci in eyes with intermediate age-related macular degeneration.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {37790320},
issn = {2693-5015},
support = {R01 EY023164/EY/NEI NIH HHS/United States ; R01 EY030614/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Intraretinal hyper-reflective foci (IHRF) are optical coherence tomography (OCT) risk factors for progression of age-related macular degeneration (AMD). In this study we assess the change in the number and distribution of IHRF over two years.<br><br>METHODS: The axial distribution of IHRF were quantified in eyes with intermediate AMD (iAMD) at baseline and 24 months, using a series of 5 sequential equidistant en face OCT retinal slabs generated between the outer border of the internal limiting membrane (ILM) and the inner border of the retinal pigment epithelium (RPE). Following thresholding and binarization, IHRF were quantified in each retinal slab using ImageJ. The change in IHRF number in each slab between baseline and month 24 was calculated.<br><br>RESULTS: Fifty-two eyes showed evidence of IHRF at baseline, and all continued to show evidence of IHRF at 24 months (M24). The total average IHRF count/eye increased significantly from 4.67 &#xb1; 0.63 at baseline to 11.62 &#xb1; 13.86 at M24 (p<0.001) with a mean increase of 6.94 &#xb1; 11.12 (range: - 9 to + 60). Overall, at M24, 76.9% eyes showed an increase in IHRF whereas 15.4% of eyes showed a decrease (4 eyes [7.6%] showed no change). There was a greater number of IHRF and a greater increase in IHRF over M24 in the outer slabs.<br><br>CONCLUSIONS: IHRF are most common in the outer retinal layers and tend to increase in number over time. The impact of the distribution and frequency of these IHRF on the overall progression of AMD requires further study.},
}
@article {pmid37787990,
year = {2023},
author = {Chantarasorn, Y and Ruamviboonsuk, P and Thoongsuwan, S and Vongkulsiri, S and Kungwanpongpun, P and Hanutsaha, P},
title = {Clinical Correlation of Retinal Fluid Fluctuation Represented by Fluctuation Index in Wet Age-Related Macular Degeneration: TOWER Study Report 2.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {10},
pages = {2},
pmid = {37787990},
issn = {2164-2591},
mesh = {Humans ; Retina/diagnostic imaging ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Diabetic Retinopathy ; },
abstract = {PURPOSE: To explore outcomes and biomarkers associated with retinal fluid instability represented by a new parameter in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Patients with treatment-na&#xef;ve nAMD receiving anti-vascular endothelial growth factor (VEGF) injections for a duration of 1 to 3 years were consecutively reviewed. Fluctuation Index (FI) of each eye, calculated by averaging the sum of differences in 1-mm central subfield thickness between each follow-up from months 3 to 24, was arranged into ascending order from the lowest to the highest and split equally into low, moderate, and high fluctuation groups. Outcomes were analyzed at 24 months.<br><br>RESULTS: Of 558 eyes, FI values showed a negative correlation with a degree-response gradient with 24-month visual improvement. After controlling for baseline best-corrected visual acuity and potential confounders, eyes with low fluctuation gained more Early Treatment Diabetic Retinopathy Study letters than those in the moderate and high fluctuation group (&#x394;, 10.1 and 14.0 letters, respectively). Significant best-corrected visual acuity improvement from baseline to month 24 (11.8 letters) was observed exclusively in the low fluctuation group despite the indifference in the number of injections and types of anti-VEGF drug used among groups. Patients presenting with central subfield thickness of &#x2265;405 &#xb5;m or intraretinal fluid coinciding with subretinal fluid showed a significant association with foveal thickness instability during the maintenance phase.<br><br>CONCLUSIONS: Apart from the central subfield thickness values, unstable macular thickening represented by the FI was associated with some baseline features and may contribute to substandard visual outcomes.<br><br>TRANSLATIONAL RELEVANCE: FI may be a valuable tool for assessing therapeutic adequacy in the treatment of nAMD.},
}
@article {pmid37787238,
year = {2023},
author = {Joshi, S and Verma, L and Ayachit, G and Salvi, R and Asad, Y and Gupta, A and Patil, A and Ayachit, A},
title = {Efficacy of a single injection of brolucizumab in neovascular age-related macular degeneration on visual acuity and micromorphometry.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {10},
pages = {3375-3380},
pmid = {37787238},
issn = {1998-3689},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Retinal Pigment Epithelium ; *Retinal Detachment/drug therapy ; Tomography, Optical Coherence/methods ; Ranibizumab/therapeutic use ; },
abstract = {PURPOSE: To assess short-term efficacy of a single injection of brolucizumab in neovascular AMD.<br><br>METHODS: This was a multicenter, retrospective chart review of 25 eyes of 25 patients who received a single injection of brolucizumab. Visual acuity (VA) and optical coherence tomography (OCT) features such as central subfield thickness (CSFT), subretinal fluid (SRF), intraretinal fluid, and pigment epithelial detachment (PED) were recorded at baseline, first month, and third month.<br><br>RESULTS: Of the 25 eyes, 14 eyes were treatment-na&#xef;ve and 11 eyes had received previous injections. VA improved from 0.68 &#xb1; 0.59 log MAR at baseline to 0.31 &#xb1; 0.43 log MAR at the end of 3 months. SRF height in first and third month was significantly reduced from baseline (P < 0.001). Subretinal hyperreflective material height significantly reduced from baseline (P value 0.008 at first month and 0.01 at third month, respectively). CSFT was 464.16 &#xb1; 247.97 microns at baseline and showed a significant reduction in first month (P < 0.001) and third month (P < 0.001). There was a significant reduction of PED height from baseline at both follow-ups. None of the eyes showed a recurrence of fluid at the end of 3 months.<br><br>CONCLUSION: Our study demonstrated sustained improvement in VA and OCT parameters after a single injection of brolucizumab at 3 months. A longer follow-up may demonstrate even farther effects of a single injection.},
}
@article {pmid37787236,
year = {2023},
author = {Hamati, J and Prashanthi, S and Narayanan, R and Sahoo, N and Das, AV and Rani, PK and Behera, UC and Khanna, R and Murthy, GVS},
title = {Prevalence of age-related macular degeneration and associated factors in Indian cohort in a tertiary care setting.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {10},
pages = {3361-3366},
pmid = {37787236},
issn = {1998-3689},
mesh = {Humans ; Aged ; Middle Aged ; Retrospective Studies ; Prevalence ; Tertiary Healthcare ; *Macular Degeneration/epidemiology ; *Diabetic Retinopathy ; *Cataract/epidemiology ; },
abstract = {PURPOSE: To report a big data analysis of risk and protective factors in patients with AMD, as well as report on the age-adjusted prevalence in a geriatric Indian cohort in a hospital setting.<br><br>METHODS: This retrospective, observational study of all patients older than 60 years of age. Multiple logistic regression was performed for the binary outcome and the presence of AMD. Variables analyzed include age, gender, socioeconomic status, occupation, urban-rural-metropolitan distribution, self-reported history of diabetes mellitus (DM), hypertension (HTN), or coronary artery disease (CAD), ocular comorbidities, history of cataract surgery, and presenting VA. Odds ratios (OR) and 99% confidence intervals were calculated.<br><br>RESULTS: Of the 608,171 patients over the age of 60 years who attended our clinics, 1.68% of subjects had a diagnosis of AMD (N = 10,217). Less than half (4,621 of 10,217 with AMD) of them were diagnosed to have dry AMD. Cataract, glaucoma, and diabetic retinopathy were associated with lower risk of AMD. Cataract surgery was associated with the higher risk of AMD (OR = 1.20; 99% CI 1.13-1.29). Smoking was not associated with AMD.<br><br>CONCLUSION: Big data analysis from a hospital setting shows that the prevalence of AMD above the age of 60 years is low. More patients with wet AMD present for treatment compared to dry AMD. Smoking was not associated with AMD in the Indian population. Cataract surgery was associated with higher prevalence of AMD.},
}
@article {pmid37787166,
year = {2024},
author = {Samanta, A and Arora, S and Jhingan, M and Singh, S and Amarasekera, S and Tucci, D and Cagini, C and Lupidi, M and Chhablani, J},
title = {Bilateral evolution of OCT biomarkers in dry AMD: Long-term follow up study.},
journal = {European journal of ophthalmology},
volume = {34},
number = {3},
pages = {683-690},
doi = {10.1177/11206721231204383},
pmid = {37787166},
issn = {1724-6016},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Retrospective Studies ; Male ; Follow-Up Studies ; Aged ; *Retinal Drusen/diagnosis ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Geographic Atrophy/diagnosis ; Aged, 80 and over ; *Biomarkers ; Fluorescein Angiography/methods ; Visual Acuity ; Disease Progression ; Middle Aged ; Multimodal Imaging ; },
abstract = {PURPOSE: To report the emergence and progress of four late-stage characteristics: incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA), drusen ooze and drusen collapse in eyes with dry age-related macular degeneration (AMD) using Spectral Domain Optical Coherence Tomography (SD-OCT).<br><br>METHODS: This was a retrospective analysis of eyes with non-exudative AMD. Multimodal imaging was done at follow up visits&#x2009;&#x2264;&#x2009;12 months. OCT volume scan was used to assess and identify the 4 characteristics. Univariate analysis was done for the various demographic and clinical characteristics.Patients with a mean age of 76.7&#x2009;&#xb1;&#x2009;10 years were followed up for 69.9&#x2009;&#xb1;&#x2009;20.6 months. iRORA, cRORA, drusen ooze was present in 15.6%, 15.6% and 15.6% of patients at baseline, respectively, and 25.0%, 40.6% and 53.1% of patients at the final follow-up, respectively. At baseline 9.1%, 0% and 9.1% of patients had bilateral drusen ooze, iRORA and cRORA, respectively. By the final follow-up, drusen collapse occurred in 46.9% and 18.8% patients in unilateral and bilateral eyes, respectively.For bilateral cases, the mean interval of time between emergence inthe two eyes for drusen ooze, drusen collapse, iRORA, and cRORA was 5&#x2009;&#xb1;&#x2009;1.4 years, 2.2&#x2009;&#xb1;&#x2009;2.2 years, 3.5&#x2009;&#xb1;&#x2009;0.7 and 1.7&#x2009;&#xb1;&#x2009;0.6 years, respectively.<br><br>CONCLUSIONS: Late-stage OCT biomarkers are seen bilaterally at 21.9% at baseline and at 56.3% at 5.8 years follow-up. Once present in one eye, cRORA had the shortest mean interval before appearance in the other eye.},
}
@article {pmid37786347,
year = {2023},
author = {Shahin, S and Tan, P and Chetsawang, J and Lu, B and Svendsen, S and Ramirez, S and Conniff, T and Alfaro, JS and Fernandez, M and Fulton, A and Laperle, AH and Svendsen, CN and Wang, S},
title = {Human Neural Progenitors Expressing GDNF Enhance Retinal Protection in a Rodent Model of Retinal Degeneration.},
journal = {Stem cells translational medicine},
volume = {12},
number = {11},
pages = {727-744},
pmid = {37786347},
issn = {2157-6580},
support = {LSP1-08235//California Institute Regenerative Medicine/ ; //Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center/ ; },
mesh = {Animals ; Humans ; Rats ; Disease Models, Animal ; Glial Cell Line-Derived Neurotrophic Factor/metabolism ; Retina/metabolism ; *Retinal Degeneration/therapy/metabolism ; Rodentia/metabolism ; Vision, Ocular ; },
abstract = {Stem cell therapy for retinal degenerative diseases has been extensively tested in preclinical and clinical studies. However, preclinical studies performed in animal models at the early stage of disease do not optimally translate to patients that present to the clinic at a later stage of disease. As the retina degenerates, inflammation and oxidative stress increase and trophic factor support declines. Testing stem cell therapies in animal models at a clinically relevant stage is critical for translation to the clinic. Human neural progenitor cells (hNPC) and hNPC engineered to stably express GDNF (hNPCGDNF) were subretinally injected into the Royal College of Surgeon (RCS) rats, a well-established model for retinal degeneration, at early and later stages of the disease. hNPCGDNF treatment at the early stage of retinal degeneration provided enhanced visual function compared to hNPC alone. Treatment with both cell types resulted in preserved retinal morphology compared to controls. hNPCGDNF treatment led to significantly broader photoreceptor protection than hNPC treatment at both early and later times of intervention. The phagocytic role of hNPC appears to support RPE cell functions and the secreted GDNF offers neuroprotection and enables the extended survival of photoreceptor cells in transplanted animal eyes. Donor cells in the RCS rat retina survived with only limited proliferation, and hNPCGDNF produced GDNF in vivo. Cell treatment led to significant changes in various pathways related to cell survival, antioxidative stress, phagocytosis, and autophagy. A combined stem cell and trophic factor therapy holds great promise for treating retinal degenerative diseases including retinitis pigmentosa and age-related macular degeneration.},
}
@article {pmid37784169,
year = {2023},
author = {Jones, CK and Li, B and Wu, JH and Nakaguchi, T and Xuan, P and Liu, TYA},
title = {Comparative analysis of alignment algorithms for macular optical coherence tomography imaging.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {60},
pmid = {37784169},
issn = {2056-9920},
abstract = {BACKGROUND: Optical coherence tomography (OCT) is the most important and commonly utilized imaging modality in ophthalmology and is especially crucial for the diagnosis and management of macular diseases. Each OCT volume is typically only available as a series of cross-sectional images (B-scans) that are accessible through proprietary software programs which accompany the OCT machines. To maximize the potential of OCT imaging for machine learning purposes, each OCT image should be analyzed en bloc as a 3D volume, which requires aligning all the cross-sectional images within a particular volume.<br><br>METHODS: A dataset of OCT B-scans obtained from 48 age-related macular degeneration (AMD) patients and 50 normal controls was used to evaluate five registration algorithms. After alignment of B-scans from each patient, an en face surface map was created to measure the registration quality, based on an automatically generated Laplace difference of the surface map-the smoother the surface map, the smaller the average Laplace difference. To demonstrate the usefulness of B-scan alignment, we trained a 3D convolutional neural network (CNN) to detect age-related macular degeneration (AMD) on OCT images and compared the performance of the model with and without B-scan alignment.<br><br>RESULTS: The mean Laplace difference of the surface map before registration was 27&#x2009;&#xb1;&#x2009;4.2 pixels for the AMD group and 26.6&#x2009;&#xb1;&#x2009;4 pixels for the control group. After alignment, the smoothness of the surface map was improved, with a mean Laplace difference of 5.5&#x2009;&#xb1;&#x2009;2.7 pixels for Advanced Normalization Tools Symmetric image Normalization (ANTs-SyN) registration algorithm in the AMD group and a mean Laplace difference of 4.3&#x2009;&#xb1;&#x2009;1.4.2 pixels for ANTs in the control group. Our 3D CNN achieved superior performance in detecting AMD, when aligned OCT B-scans were used (AUC 0.95 aligned vs. 0.89 unaligned).<br><br>CONCLUSIONS: We introduced a novel metric to quantify OCT B-scan alignment and compared the effectiveness of five alignment algorithms. We confirmed that alignment could be improved in a statistically significant manner with readily available alignment algorithms that are available to the public, and the ANTs algorithm provided the most robust performance overall. We further demonstrated that alignment of OCT B-scans will likely be useful for training 3D CNN models.},
}
@article {pmid37783334,
year = {2023},
author = {Sheibani, N and Song, YS and Farnoodian, M and Inampudi, S and Wang, S and Darjatmoko, SR and Sorenson, CM},
title = {Artesunate mitigates choroidal neovascularization and scar formation.},
journal = {Experimental eye research},
volume = {236},
number = {},
pages = {109666},
doi = {10.1016/j.exer.2023.109666},
pmid = {37783334},
issn = {1096-0007},
mesh = {Humans ; Animals ; Mice ; *Vascular Endothelial Growth Factor A/metabolism ; Artesunate/therapeutic use ; Cicatrix/prevention &amp; control/pathology ; Endothelial Cells/metabolism ; *Choroidal Neovascularization/drug therapy/prevention &amp; control/etiology ; Vascular Endothelial Growth Factors ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {Angiogenesis, although required during eye development, has a causative effect in many ocular diseases. Aberrant neovascularization contributes to the progression of neovascular age-related macular degeneration (nAMD), a vision-threaten disease in aging Americans. Since increased amounts of vascular endothelial growth factor (VEGF) drives neovascularization during the pathogenesis of nAMD the standard of care are anti-VEGF therapies attempt to disrupt this vicious cycle. These current anti-VEGF therapies try to maintain vascular homeostasis while abating aberrant neovascularization but regrettably don't prevent fibrosis or scar formation. In addition, some patients demonstrate an incomplete response to anti-VEGF therapy as demonstrated by progressive vision loss. Here, we show choroidal endothelial cells (ChEC) incubated with artesunate demonstrated decreased migration and inflammatory and fibrotic factor expression, which corresponded with decreased sprouting in a choroid/retinal pigment epithelium (RPE) explant sprouting angiogenesis assay. To assess the efficacy of artesunate to curtail neovascularization in vivo, we utilized laser photocoagulation-induced rupture of the Bruch's membrane to induce choroidal neovascularization (CNV). Artesunate significantly inhibited CNV and the accompanying fibrotic scar, perhaps due in part to its ability to inhibit mononuclear phagocyte (MP) recruitment. Thus, artesunate shows promise in inhibiting both CNV and fibrosis.},
}
@article {pmid37782954,
year = {2024},
author = {Shaw, L and Khanna, S and Hyman, MJ and Ham, S and Blitzer, A and Parvar, SP and Soo, J and Flores, A and Hariprasad, S and Skondra, D},
title = {INTERACTIONS OF METFORMIN AND OTHER MEDICATIONS IN REDUCING THE ODDS OF AGE-RELATED MACULAR DEGENERATION IN A COHORT OF PATIENTS WITH DIABETES.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {2},
pages = {197-204},
doi = {10.1097/IAE.0000000000003949},
pmid = {37782954},
issn = {1539-2864},
support = {Core Grant//The University of Chicago Institute for Translational Medicine (ITM)/ ; Pilot Grant//The University of Chicago Institute for Translational Medicine (ITM)/ ; },
mesh = {Humans ; Aged ; United States/epidemiology ; *Metformin/therapeutic use ; Medicare ; *Diabetes Mellitus/drug therapy/epidemiology ; Sulfonylurea Compounds/therapeutic use ; Insulin/therapeutic use ; *Macular Degeneration/drug therapy/prevention &amp; control/chemically induced ; },
abstract = {PURPOSE: A previous study from our group demonstrated protective effects of the use of metformin in the odds of developing age-related macular degeneration (AMD). This is a subgroup analysis in a cohort of patients with diabetes to assess the interaction of metformin and other medications in protecting diabetic patients against developing AMD.<br><br>METHODS: This is a case-control analysis using data from the Merative MarketScan Commercial and Medicare databases. Patients were 55 years and older with newly diagnosed AMD and matched to controls. We performed multivariable conditional logistic regressions, which adjusted for known risk factors of AMD and tested multiple interaction effects between metformin and 1) insulin, 2) sulfonylureas, 3) glitazones, 4) meglitinides, and 5) statins.<br><br>RESULTS: The authors identified 81,262 diabetic cases and 79,497 diabetic controls. Metformin, insulin, and sulfonylureas demonstrated independent protective effects against AMD development. Sulfonylureas in combination with metformin demonstrated further decreased odds of AMD development compared with metformin alone. The other medication group (exenatide, sitagliptin, and pramlintide) slightly increased the odds of developing AMD when taken alone, but the combination with metformin alleviated this effect.<br><br>CONCLUSION: The authors believe that their results bring them one step closer to finding an optimal effective hypoglycemic regimen that also protects against AMD development in diabetic patients.},
}
@article {pmid37780745,
year = {2023},
author = {Zhao, T and Li, J and Wang, Y and Guo, X and Sun, Y},
title = {Integrative metabolome and lipidome analyses of plasma in neovascular macular degeneration.},
journal = {Heliyon},
volume = {9},
number = {10},
pages = {e20329},
pmid = {37780745},
issn = {2405-8440},
abstract = {Age-related macular degeneration (AMD) causes irreversible vision-loss among the elderly in industrial countries. Neovascular AMD (nAMD), which refers to late-stage AMD, is characterized by severe vision-threatening choroidal neovascularization (CNV). Herein, we constructed a global metabolic network of nAMD, based on untargeted metabolomic and lipidomic analysis of plasma samples collected from sixty subjects (30 nAMD patients and 30 age-matched controls). Among the nAMD and control groups, 62 and 44 significantly different metabolites were detected in the positive and negative ion modes, respectively. Grouping analysis further showed that lipid and lipid-like molecule-based superclasses contained the highest number of significantly different metabolites. Lipidomic analysis revealed that 53 lipids among the nAMD and control groups differed significantly; these belonged to four major lipid categories (glycerophospholipids, sphingolipids, glycerolipids, and fatty acids). A discriminative biomarker panel comprising 16 metabolites and lipids, which was constructed using multivariate statistical machine learning methods, could effectively identify nAMD cases. Among these 16 compounds, eight were lipids that belonged to three lipid categories (glycerophospholipids, sphingolipids, and prenol lipids). The top three biomarkers with the highest importance scores were all lipids (a glycerophospholipid and two sphingolipids), highlighting the crucial role played by glycerophospholipid and sphingolipid pathways in nAMD. These differences between the metabolic and lipid profiles of nAMD patients and elderly individuals without AMD provide a readout of the overall metabolic status of nAMD. Further insights into the identified discriminative biomarkers may pave the way for future diagnostic and therapeutic interventions for nAMD.},
}
@article {pmid37779414,
year = {2025},
author = {Shetty, S and Singh, K and Barve, K},
title = {Therapeutic Management and New Upcoming Approaches for Age Related Macular Degeneration.},
journal = {Current drug research reviews},
volume = {17},
number = {1},
pages = {59-75},
pmid = {37779414},
issn = {2589-9783},
mesh = {Humans ; *Macular Degeneration/therapy/etiology ; Dietary Supplements ; Antioxidants/therapeutic use ; Animals ; Risk Factors ; },
abstract = {Age-related Macular Degeneration (AMD) is a severe eye illness that is going to lead in the race for incurable blindness globally among the elderly population. AMD is the third common reason responsible for affecting the quality of life globally. The macula and the retinal layers are adversely affected during AMD and are responsible for the loss of vision eventually. Numerous genetic variables, lipid metabolism, ageing and oxidative damage are the causative factors in the genesis of AMD. Lack of antioxidants, smoking and excessive alcohol intake contribute to increasing the risk of AMD. Management of dry AMD involves the use of nutritional supplements like zinc and antioxidants, along with conventional treatment, however, the use of nutritional supplements can only give minor benefits on the progression of dry AMD. Later stages of AMD need to be managed by cell-based interventions where the damaged or lost cells are replaced with fresh donor cells. A plethora of treatment methods are used in the management of AMD, such as nutrition, antibody-based treatments, stem cell management and nanotherapeutics. The available expensive treatments come with a number of adverse effects and future developments require the involvement of risk factor modification approaches, personalized therapy, targeting the disease specific pathways, exploring better anti-vascular endothelial growth factor (VEGF) inhibitors and many other regenerative approaches, that will broaden techniques to diagnose, control and treat AMD. This review provides an overview of the progression of AMD and the causative factors, with considerable emphasises on the current and potential prospects.},
}
@article {pmid37778330,
year = {2023},
author = {Zhou, L and Ho, BM and Chan, HYE and Tong, Y and Du, L and He, JN and Ng, DS and Tham, CC and Pang, CP and Chu, WK},
title = {Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.},
journal = {Journal of innate immunity},
volume = {15},
number = {1},
pages = {739-750},
pmid = {37778330},
issn = {1662-8128},
mesh = {Humans ; DNA ; Immunity, Innate ; *Inflammation ; *Nucleotidyltransferases/metabolism ; *Signal Transduction ; *Membrane Proteins/metabolism ; },
abstract = {Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.},
}
@article {pmid37777762,
year = {2023},
author = {Enoch, J and Ghulakhszian, A and Sekhon, M and Crabb, DP and Taylor, DJ and Dinah, C},
title = {Piloting a forced-choice task to elicit treatment preferences in geographic atrophy.},
journal = {BMC research notes},
volume = {16},
number = {1},
pages = {244},
pmid = {37777762},
issn = {1756-0500},
support = {Higher Education Innovation Fund//City, University of London/ ; AMR-000001//Apellis Pharmaceuticals/ ; },
mesh = {Humans ; *Geographic Atrophy/drug therapy ; *Macular Degeneration/drug therapy ; },
abstract = {OBJECTIVE: Geographic Atrophy (GA) is the advanced form of the non-neovascular ('dry') type of age-related macular degeneration (AMD) and responsible for one-quarter of legal blindness in the UK. New therapies delivered by intravitreal injection are in late-stage development, and two such therapies (pegcetacoplan (Syfovre) and avacincaptad pegol (Izervay)) have now been approved for clinical use by the US Food and Drug Administration. These therapies slow down, but do not stop or reverse, progression of GA and they may also increase the risk of developing the neovascular ('wet') type of AMD. Within a larger study exploring the acceptability of these new treatments to people living with GA, we developed a forced-choice exercise to evaluate how participants weigh up benefits and drawbacks of different treatment regimens. This research note reports quantitative and qualitative findings from this exercise.<br><br>RESULTS: Twenty-eight participants took part in this exercise. The exercise demonstrated that participants were generally, although not unanimously, in favour of less frequent treatment for GA that was slightly less efficacious in terms of preserving visual function but presented a lower risk of developing wet AMD. Even among a small sample, the exercise demonstrated the highly personal and idiosyncratic decision-making processes influencing participants' choices of preferred hypothetical GA treatment.},
}
@article {pmid37776965,
year = {2023},
author = {Siriwardane, DA and Jiang, W and Mudalige, T},
title = {Profiling in-vitro release of verteporfin from VISUDYNE® liposomal formulation and investigating verteporfin binding to human serum albumin.},
journal = {International journal of pharmaceutics},
volume = {646},
number = {},
pages = {123449},
doi = {10.1016/j.ijpharm.2023.123449},
pmid = {37776965},
issn = {1873-3476},
abstract = {VISUDYNE® is a liposomal formulation of verteporfin, used in the photodynamic therapy of age-related macular degeneration via intravenous administration. In this study, we developed a new in vitro method to quantify verteporfin release from VISUDYNE® under conditions that replicate in vivo conditions using human serum albumin (HSA). Verteporfin release from the liposomes was quantified using capillary electrophoresis (CE) with optical detection. Verteporfin binding to HSA was quantified by measuring HSA fluorescence that is quenched by drugs binding to specific HSA binding sites. The binding constant of verteporfin to HSA was calculated using the Stern Volmer plot and found to be 1.966 × 10[7] M[-1] at 37 °C. Verteporfin binding to HSA involves one albumin binding site and the binding molar ratio between verteporfin and HSA is approximately 1:1. A rapid partitioning of verteporfin from VISUDYNE® onto HSA takes place within 10 min and involves the release of more than 90% of the verteporfin at physiological temperatures. This study verifies this approach of using CE to rapidly separate liposome and HSA-bound drug, thus minimizing drug release artifacts created with other methods.},
}
@article {pmid37776863,
year = {2023},
author = {Castiglione, GM and Chiu, YLI and Gutierrez, EA and Van Nynatten, A and Hauser, FE and Preston, M and Bhattacharyya, N and Schott, RK and Chang, BSW},
title = {Convergent evolution of dim light vision in owls and deep-diving whales.},
journal = {Current biology : CB},
volume = {33},
number = {21},
pages = {4733-4740.e4},
doi = {10.1016/j.cub.2023.09.015},
pmid = {37776863},
issn = {1879-0445},
mesh = {Animals ; *Strigiformes/metabolism ; Retinaldehyde/metabolism ; Whales ; Retinal Rod Photoreceptor Cells ; Retina/metabolism ; *Retinal Degeneration/genetics/metabolism ; Rhodopsin/metabolism ; },
abstract = {Animals with enhanced dim-light sensitivity are at higher risk of light-induced retinal degeneration when exposed to bright light conditions.[1][,][2][,][3][,][4] This trade-off is mediated by the rod photoreceptor sensory protein, rhodopsin (RHO), and its toxic vitamin A chromophore by-product, all-trans retinal.[5][,][6][,][7][,][8] Rod arrestin (Arr-1) binds to RHO and promotes sequestration of excess all-trans retinal,[9][,][10] which has recently been suggested as a protective mechanism against photoreceptor cell death.[2][,][11] We investigated Arr-1 evolution in animals at high risk of retinal damage due to periodic bright-light exposure of rod-dominated retinas. Here, we find the convergent evolution of enhanced Arr-1/RHO all-trans-retinal sequestration in owls and deep-diving whales. Statistical analyses reveal a parallel acceleration of Arr-1 evolutionary rates in these lineages, which is associated with the introduction of a rare Arr-1 mutation (Q69R) into the RHO-Arr-1 binding interface. Using in vitro assays, we find that this single mutation significantly enhances RHO-all-trans-retinal sequestration by ∼30%. This functional convergence across 300 million years of evolutionary divergence suggests that Arr-1 and RHO may play an underappreciated role in the photoprotection of the eye, with potentially vast clinical significance.},
}
@article {pmid37776460,
year = {2024},
author = {Palanisamy, K and Chidambaram, S},
title = {An In Vitro Bilayer Model of Human Primary Retinal Pigment Epithelial and Choroid Endothelial Cells for Permeability Studies.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2711},
number = {},
pages = {205-223},
pmid = {37776460},
issn = {1940-6029},
mesh = {Humans ; *Endothelial Cells ; *Choroid ; Retina ; Blood-Retinal Barrier ; Retinal Pigment Epithelium ; },
abstract = {The blood-retinal barrier (BRB) present in the posterior chamber of the eye plays a major role in maintaining the proper function and integrity of the retina. Retinal pigment epithelium and choriocapillaris form the outer blood retinal barrier (oBRB), and breakdown of this barrier leads to vision-threatening diseases like macular edema, macular degeneration, and diabetic retinopathy. A simplified cell culture model of oBRB will be of great importance in elucidating the molecular mechanism of the disease progression. This chapter describes methods for primary cell isolation from donor eyes to culture human retinal pigment epithelial cells (hRPE) and choroidal endothelial cells (hCEC) and the protocol for construction of a simplified in vitro model of oBRB on fibronectin-coated Transwell inserts. Further, we explained the permeability study using FITC-dextran conjugated tracers for validating the bilayer model. The permeability experiments ensured that the system could easily be manipulated to recapitulate the pathological condition in vitro. Thus, it would be an optimal system for studying the disease mechanisms related to retinal and choroidal pathologies, for screening small molecules, and for performing drug permeability kinetics. Moreover, fundamental understanding of paracellular and transcellular trafficking of cargo in hRPE and hCEC could also be studied using this model.},
}
@article {pmid37776074,
year = {2024},
author = {Airody, A and Baseler, HA and Seymour, J and Allgar, V and Mukherjee, R and Downey, L and Dhar-Munshi, S and Mahmood, S and Balaskas, K and Empeslidis, T and Hanson, RLW and Dorey, T and Szczerbicki, T and Sivaprasad, S and Gale, RP},
title = {Treatment of age-related macular degeneration with aflibercept using a treat, extend and fixed protocol; A 4-year study of treatment outcomes, durability, safety and quality of life (An extension to the MATE randomised controlled trial).},
journal = {Acta ophthalmologica},
volume = {102},
number = {3},
pages = {e328-e338},
doi = {10.1111/aos.15774},
pmid = {37776074},
issn = {1755-3768},
support = {Investigator-led Independent grant//Bayer PLC/ ; },
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Quality of Life ; Prospective Studies ; Visual Acuity ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Macular Degeneration/drug therapy ; Treatment Outcome ; Recombinant Fusion Proteins/therapeutic use ; Randomized Controlled Trials as Topic ; Observational Studies as Topic ; },
abstract = {PURPOSE: Data are limited pertaining to the long-term benefits of aflibercept treatment for neovascular age-related macular degeneration (nAMD). The aim of this study was to provide outcomes, safety, durability and quality-of-life data with aflibercept using a modified treat, extend and fixed regime over 4 years.<br><br>METHODS: Prospective, multicentre, single cohort observational study of treatment-na&#xef;ve nAMD participants treated with aflibercept as 2-year extension of the MATE-trial that compared early and late Treat-and-Extend for 2&#x2009;years. Refracted ETDRS best corrected visual acuity (BCVA), central retinal thickness (CRT), treatment interval and adverse events were assessed. Quality-of-life was measured using the Macular Disease Dependent Quality of Life (MacDQoL) and Macular Disease Treatment Satisfaction Questionnaires (MacTSQ).<br><br>RESULTS: Twenty-six of 40 participants completing the MATE-trial were enrolled with 20 completing the total 4-year study. Mean BCVA was 60.7 at Month 0 and 64.8 ETDRS letters at Month 48 while CRT decreased from 423.7&#x2009;&#x3bc;m to 292.2&#x2009;&#x3bc;m. Five participants discontinued treatment due to inactivity. The mean number of treatments and visits for the remaining participants was 27 and 30.0, respectively, with treatment intervals extended to 12&#x2009;weeks in four participants at Month 48. Both AMD-specific QoL and treatment satisfaction remained stable between Months 0 and 48 and mean BCVA significantly correlated with AMD-specific QoL scores at Months 12, 24 and 48.<br><br>CONCLUSIONS: Results suggest that BCVA can be maintained over 48&#x2009;months when following a treat-extend-and-fix regimen of aflibercept with intervals out to 12&#x2009;weeks, while maintaining AMD-specific QoL and treatment satisfaction.},
}
@article {pmid37775259,
year = {2024},
author = {Mares, V and Schmidt-Erfurth, UM and Leingang, O and Fuchs, P and Nehemy, MB and Bogunovic, H and Barthelmes, D and Reiter, GS},
title = {Approved AI-based fluid monitoring to identify morphological and functional treatment outcomes in neovascular age-related macular degeneration in real-world routine.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {7},
pages = {971-977},
doi = {10.1136/bjo-2022-323014},
pmid = {37775259},
issn = {1468-2079},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use ; *Visual Acuity/physiology ; Male ; Female ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; *Artificial Intelligence ; *Subretinal Fluid ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Ranibizumab/therapeutic use/administration &amp; dosage ; Follow-Up Studies ; Retrospective Studies ; },
abstract = {AIM: To predict antivascular endothelial growth factor (VEGF) treatment requirements, visual acuity and morphological outcomes in neovascular age-related macular degeneration (nAMD) using fluid quantification by artificial intelligence (AI) in a real-world cohort.<br><br>METHODS: Spectral-domain optical coherence tomography data of 158 treatment-na&#xef;ve patients with nAMD from the Fight Retinal Blindness! registry in Zurich were processed at baseline, and after initial treatment using intravitreal anti-VEGF to predict subsequent 1-year and 4-year outcomes. Intraretinal and subretinal fluid and pigment epithelial detachment volumes were segmented using a deep learning algorithm (Vienna Fluid Monitor, RetInSight, Vienna, Austria). A predictive machine learning model for future treatment requirements and morphological outcomes was built using the computed set of quantitative features.<br><br>RESULTS: Two hundred and two eyes from 158 patients were evaluated. 107 eyes had a lower median (&#x2264;7) and 95 eyes had an upper median (&#x2265;8) number of injections in the first year, with a mean accuracy of prediction of 0.77 (95% CI 0.71 to 0.83) area under the curve (AUC). Best-corrected visual acuity at baseline was the most relevant predictive factor determining final visual outcomes after 1&#x2009;year. Over 4&#x2009;years, half of the eyes had progressed to macular atrophy (MA) with the model being able to distinguish MA from non-MA eyes with a mean AUC of 0.70 (95% CI 0.61 to 0.79). Prediction for subretinal fibrosis reached an AUC of 0.74 (95% CI 0.63 to 0.81).<br><br>CONCLUSIONS: The regulatory approved AI-based fluid monitoring allows clinicians to use automated algorithms in prospectively guided patient treatment in AMD. Furthermore, retinal fluid localisation and quantification can predict long-term morphological outcomes.},
}
@article {pmid37774953,
year = {2023},
author = {Chacin Ruiz, EA and Swindle-Reilly, KE and Ford Versypt, AN},
title = {Experimental and mathematical approaches for drug delivery for the treatment of wet age-related macular degeneration.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {363},
number = {},
pages = {464-483},
pmid = {37774953},
issn = {1873-4995},
support = {R01 EB032870/EB/NIBIB NIH HHS/United States ; R35 GM133763/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Vascular Endothelial Growth Factor A ; Drug Delivery Systems/methods ; *Wet Macular Degeneration/drug therapy ; Hydrogels/therapeutic use ; Polymers/therapeutic use ; Intravitreal Injections ; },
abstract = {Several chronic eye diseases affect the posterior segment of the eye. Among them age-related macular degeneration can cause vision loss if left untreated and is one of the leading causes of visual impairment in the world. Most treatments are based on intravitreally injected therapeutics that inhibit the action of vascular endothelial growth factor. However, due to the need for monthly injections, this method is associated with poor patient compliance. To address this problem, numerous drug delivery systems (DDSs) have been developed. This review covers a selection of particulate systems, non-stimuli responsive hydrogels, implants, and composite systems that have been developed in the last few decades. Depending on the type of DDS, polymer material, and preparation method, different mechanical properties and drug release profiles can be achieved. Furthermore, DDS development can be optimized by implementing mathematical modeling of both drug release and pharmacokinetic aspects. Several existing mathematical models for diffusion-controlled, swelling-controlled, and erosion-controlled drug delivery from polymeric systems are summarized. Compartmental and physiologically based models for ocular drug transport and pharmacokinetics that have studied drug concentration profiles after intravitreal delivery or release from a DDS are also reviewed. The coupling of drug release models with ocular pharmacokinetic models can lead to obtaining much more efficient DDSs for the treatment of age-related macular degeneration and other diseases of the posterior segment of the eye.},
}
@article {pmid37773500,
year = {2023},
author = {Sazhnyev, Y and Sin, TN and Ma, A and Chang, E and Huynh, L and Roszak, K and Park, S and Choy, K and Farsiu, S and Moshiri, A and Thomasy, SM and Yiu, G},
title = {Choroidal Changes in Rhesus Macaques in Aging and Age-Related Drusen.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {12},
pages = {44},
pmid = {37773500},
issn = {1552-5783},
support = {R21 EY031108/EY/NEI NIH HHS/United States ; P51 OD011107/OD/NIH HHS/United States ; R01 EY032238/EY/NEI NIH HHS/United States ; P30 EY012576/EY/NEI NIH HHS/United States ; U24 EY029904/EY/NEI NIH HHS/United States ; R01 EY033733/EY/NEI NIH HHS/United States ; P30 EY005722/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Animals ; Macaca mulatta ; Retrospective Studies ; Retina ; Choroid/blood supply ; Aging ; *Macular Degeneration ; *Retinal Drusen ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: Choroidal vascular changes occur with normal aging and age-related macular degeneration (AMD). Here, we evaluate choroidal thickness and vascularity in aged rhesus macaques to better understand the choroid's role in this nonhuman primate model of AMD.<br><br>METHODS: We analyzed optical coherence tomography (OCT) images of 244 eyes from 122&#xa0;rhesus macaques (aged 4-32&#xa0;years) to measure choroidal thickness (CT) and choroidal vascularity index (CVI). Drusen number, size, and volume were measured by semiautomated annotation and segmentation of OCT images. We performed regression analyses to determine any association of CT or CVI with age, sex, and axial length and to determine if the presence and volume of soft drusen impacted these choroidal parameters.<br><br>RESULTS: In rhesus macaques, subfoveal CT decreased with age at 3.2 &#xb5;m/y (R2 = 0.481, P < 0.001), while CVI decreased at 0.66% per year (R2 = 0.257, P < 0.001). Eyes with soft drusen exhibited thicker choroid (179.9 &#xb1; 17.5 &#xb5;m vs. 162.0 &#xb1; 27.9 &#xb5;m, P < 0.001) and higher CVI (0.612 &#xb1; 0.051 vs. 0.577 &#xb1; 0.093, P = 0.005) than age-matched control animals. Neither CT or CVI appeared to be associated with drusen number, size, or volume in this cohort. However, some drusen in macaques were associated with underlying choroidal vessel enlargement resembling pachydrusen in human patients with AMD.<br><br>CONCLUSIONS: Changes in the choroidal vasculature in rhesus macaques resemble choroidal changes in human aging, but eyes with drusen exhibit choroidal thickening, increased vascularity, and phenotypic characteristics of pachydrusen observed in some patients with AMD.},
}
@article {pmid37773477,
year = {2023},
author = {Lad, EM and Finger, RP and Guymer, R},
title = {Biomarkers for the Progression of Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {6},
pages = {2917-2941},
pmid = {37773477},
issn = {2193-8245},
abstract = {Age-related macular degeneration (AMD) is a leading cause of severe vision loss worldwide, with a global prevalence that is predicted to substantially increase. Identifying early biomarkers indicative of progression risk will improve our ability to assess which patients are at greatest risk of progressing from intermediate AMD (iAMD) to vision-threatening late-stage AMD. This is key to ensuring individualized management and timely intervention before substantial structural damage. Some structural biomarkers suggestive of AMD progression risk are well established, such as changes seen on color fundus photography and more recently optical coherence tomography (drusen volume, pigmentary abnormalities). Emerging biomarkers identified through multimodal imaging, including reticular pseudodrusen, hyperreflective foci, and drusen sub-phenotypes, are being intensively explored as risk factors for progression towards late-stage disease. Other structural biomarkers merit further research, such as ellipsoid zone reflectivity and choriocapillaris flow features. The measures of visual function that best detect change in iAMD and correlate with risk of progression remain under intense investigation, with tests such as dark adaptometry and cone-specific contrast tests being explored. Evidence on blood and plasma markers is preliminary, but there are indications that changes in levels of C-reactive protein and high-density lipoprotein cholesterol may be used to stratify patients and predict risk. With further research, some of these biomarkers may be used to monitor progression. Emerging artificial intelligence methods may help evaluate and validate these biomarkers; however, until we have large and well-curated longitudinal data sets, using artificial intelligence effectively to inform clinical trial design and detect outcomes will remain challenging. This is an exciting area of intense research, and further work is needed to establish the most promising biomarkers for disease progression and their use in clinical care and future trials. Ultimately, a multimodal approach may yield the most accurate means of monitoring and predicting future progression towards vision-threatening, late-stage AMD.},
}
@article {pmid37773436,
year = {2024},
author = {Nam, SW and Noh, H and Yoon, JM and Kong, M and Ham, DI},
title = {Macular lesions associated with age-related macular degeneration in pachydrusen eyes.},
journal = {Eye (London, England)},
volume = {38},
number = {4},
pages = {691-697},
pmid = {37773436},
issn = {1476-5454},
mesh = {Humans ; Middle Aged ; Aged ; Retrospective Studies ; Tomography, Optical Coherence/methods ; *Macular Degeneration/complications/diagnosis/pathology ; *Retinal Drusen/diagnosis/epidemiology/pathology ; Retina/pathology ; *Geographic Atrophy/diagnosis/epidemiology ; Neovascularization, Pathologic/complications/pathology ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND: To investigate the prevalence of macular lesions associated with age-related macular degeneration (AMD) in eyes with pachydrusen.<br><br>METHODS: Clinical records and multimodal imaging data of patients over 50 years old with drusen or drusenoid deposits were retrospectively assessed, and eyes with pachydrusen were included in this study. The presence of AMD features, including drusen or drusenoid deposits, macular pigmentary abnormalities, geographic atrophy (GA), and macular neovascularization (MNV), were evaluated.<br><br>RESULTS: Out of 967 eyes of 494 patients with drusen or drusenoid deposits, 330 eyes of 183 patients had pachydrusen (34.1%). The mean age was 66.1&#x2009;&#xb1;&#x2009;9.3 years, and the subfoveal choroidal thickness (SFCT) was 292.7&#x2009;&#xb1;&#x2009;100.1&#x2009;&#x3bc;m. The mean number of pachydrusen per eye was 2.22&#x2009;&#xb1;&#x2009;1.73. The majority of eyes with pachydrusen had no other drusen or drusenoid deposits (95.2%). Only 16 eyes (4.8%) had other deposits, including soft drusen (10 eyes, 3.0%), cuticular drusen (3 eyes, 0.9%), and reticular pseudodrusen (RPD; 3 eyes, 0.9%). Macular pigmentary abnormalities accompanied pachydrusen in 68 eyes (27.4%). None of the eyes had GA, and 82 eyes (24.8%) had MNV. The majority of MNV was polypoidal choroidal vasculopathy (PCV; 65 eyes, 19.7%), followed by type 1 (10 eyes, 3.0%), type 2 (5 eyes, 1.5%), and type 3 MNV (2 eyes, 0.6%).<br><br>CONCLUSIONS: Eyes with pachydrusen in Korean population have several characteristic AMD lesions in low frequencies. These findings indicate that pachydrusen might have diagnostic and prognostic values that are different from those of other drusen or drusenoid deposits.},
}
@article {pmid37773435,
year = {2024},
author = {Amoaku, WM and Cushley, L and Silvestri, V and Akafo, S and Amissah-Arthur, KN and Lartey, S and Hageman, CN and Pappas, CM and Hubbard, WC and Bernstein, PS and Vitale, A and Roberts, M and Virgili, G and Hageman, GS and Silvestri, G and , },
title = {Vitreomacular interface abnormalities in the Ghanaian African.},
journal = {Eye (London, England)},
volume = {38},
number = {3},
pages = {578-584},
pmid = {37773435},
issn = {1476-5454},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; },
mesh = {Adult ; Humans ; Female ; Male ; Ghana/epidemiology ; Vitreous Body ; *Macula Lutea ; Prospective Studies ; Cross-Sectional Studies ; *Vitreous Detachment/epidemiology ; *Eye Diseases ; *Macular Degeneration ; Tomography, Optical Coherence/methods ; Retrospective Studies ; },
abstract = {BACKGROUND/OBJECTIVE: Describe vitreomacular interface abnormalities (VMIA) using spectral-domain optical coherence tomography (SD-OCT), and correlations with age-related macular degeneration (AMD) grade in Ghanaian Africans.<br><br>SUBJECTS/METHODS: Prospective, cross-sectional study of adults aged &#x2265;50 years recruited in Ghana AMD Study. Participant demographics, medical histories, ophthalmic examination, digital colour fundus photography (CFP) were obtained. High-resolution five-line raster OCT, Macular Cube 512&#x2009;&#xd7;&#x2009;128 scans, and additional line scans in areas of clinical abnormality, were acquired. SD-OCT VMI features classified by International Vitreomacular Traction Study Group system and relationships to AMD grade were evaluated.<br><br>OUTCOMES: VMIA prevalence, posterior vitreous detachment (PVD), vitreomacular adhesions (VMA), vitreomacular traction (VMT), epiretinal membranes (ERM), correlations with AMD grade.<br><br>RESULTS: The full Ghana AMD cohort included 718 participants; 624 participants (1248 eyes) aged &#x2265;50 years (range = 50-101, mean = 68.8), 68.9% female were included in this analysis. CFP with OCT scans were available for 776 eyes (397 participants); 707 (91.1%) had gradable CFP and OCT scans for both AMD and VMI grading forming the dataset for this report. PVD was absent in 504 (71.3%); partial and complete PVD occurred in 16.7% and 12.0% respectively. PVD did not increase with age (p&#x2009;=&#x2009;0.720). VMIA without traction and macular holes were observed in 12.2% of eyes; 87.8% had no abnormalities. VMIA was not significantly correlated with AMD grade (p&#x2009;=&#x2009;0.819).<br><br>CONCLUSIONS: This provides the first assessment of VMIA in Ghanaian Africans. VMIA are common in Africans; PVD may be less common than in Caucasians. There was no significant association of AMD grade with VMIA.},
}
@article {pmid37772657,
year = {2023},
author = {Tao, T and Xu, N and Li, J and Zhao, M and Li, X and Huang, L},
title = {Conditional loss of Ube3d in the retinal pigment epithelium accelerates age-associated alterations in the retina of mice.},
journal = {The Journal of pathology},
volume = {261},
number = {4},
pages = {442-454},
doi = {10.1002/path.6201},
pmid = {37772657},
issn = {1096-9896},
support = {81670870//National Natural Science Foundation of China/ ; 82171060//National Natural Science Foundation of China/ ; 2019-RC-HL-019//Science and Technology Innovation Project of Chinese Academy of Medical Sciences/ ; },
mesh = {Mice ; Humans ; Animals ; *Retinal Pigment Epithelium/metabolism ; Retina/metabolism ; *Macular Degeneration/genetics/pathology ; Phagocytosis ; Mice, Knockout ; Proteasome Endopeptidase Complex/metabolism ; },
abstract = {Several studies have suggested a correlation between the ubiquitin-proteasome system (UPS) and age-related macular degeneration (AMD), with its phenotypic severity ranging from mild visual impairment to blindness, but the mechanism for UPS dysfunction contributing to disease progression is unclear. In this study, we investigated the role of ubiquitin protein ligase E3D (UBE3D) in aging and degeneration in mouse retina. Conditional knockout of Ube3d in the retinal pigment epithelium (RPE) of mice led to progressive and irregular fundus lesions, attenuation of the retinal vascular system, and age-associated deterioration of rod and cone responses. Simultaneously, RPE-specific Ube3d knockout mice also presented morphological changes similar to the histopathological characteristics of human AMD, in which a defective UPS led to RPE abnormalities such as phagocytosis or degradation of metabolites, the interaction with photoreceptor outer segment, and the transport of nutrients or waste products with choroidal capillaries via Bruch's membrane. Moreover, conditional loss of Ube3d resulted in aberrant molecular characterizations associated with the autophagy-lysosomal pathway, oxidative stress damage, and cell-cycle regulation, which are implicated in AMD pathology. Thus, our findings strengthen and expand the impact of UPS dysfunction on retinal pathophysiology during aging, indicating that genetic Ube3d deficiency in the RPE could lead to the abnormal formation of pigment deposits and secondary fundus alterations. © 2023 The Authors. The Journal of Pathology published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.},
}
@article {pmid37768678,
year = {2023},
author = {Davuluri, S and Vempuluru, VS and Shields, CL},
title = {Amelanotic Fundus Lesion in an Older White Woman.},
journal = {JAMA ophthalmology},
volume = {141},
number = {11},
pages = {1081-1082},
doi = {10.1001/jamaophthalmol.2023.4325},
pmid = {37768678},
issn = {2168-6173},
mesh = {Female ; Humans ; *Fundus Oculi ; *Eye Diseases/diagnosis ; },
}
@article {pmid37768527,
year = {2023},
author = {Fantaguzzi, F and Tombolini, B and Servillo, A and Zucchiatti, I and Sacconi, R and Bandello, F and Querques, G},
title = {Shedding Light on Photobiomodulation Therapy for Age-Related Macular Degeneration: A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {6},
pages = {2903-2915},
pmid = {37768527},
issn = {2193-8245},
abstract = {BACKGROUND: Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD.<br><br>METHODS: A comprehensive search was conducted using the PubMed database, employing the keywords "photobiomodulation" and "age-related macular degeneration." All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review.<br><br>RESULTS: The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients&#xa0;with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials.<br><br>CONCLUSIONS: Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain.},
}
@article {pmid37768273,
year = {2023},
author = {Kar, D and Corradetti, G and Swain, TA and Clark, ME and McGwin, G and Owsley, C and Sadda, SR and Curcio, CA},
title = {Choriocapillaris Impairment Is Associated With Delayed Rod-Mediated Dark Adaptation in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {12},
pages = {41},
pmid = {37768273},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Dark Adaptation ; *Macular Degeneration ; Retina ; *Retinal Drusen ; Tomography, Optical Coherence/methods ; Choroid ; },
abstract = {PURPOSE: Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD.<br><br>METHODS: One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied. AMD presence and severity was determined using the Age-Related Eye Disease Study (AREDS) grading system. FD% was quantified using macular spectral domain optical coherence tomography angiography (OCTA) scans. Vision tests included rod-mediated dark adaptation (RMDA), best-corrected visual acuity, and contrast sensitivity (photopic and mesopic), and microperimetric light sensitivity (scotopic, mesopic, and photopic). Presence of subretinal drusenoid deposits (SDD) was determined using multimodal imaging.<br><br>RESULTS: In 410 study eyes of 410 participants (mean [SD] age = 71.7 years [5.9]), FD% was higher in early AMD (mean [SD] = 54.0% [5.5], N = 122) and intermediate AMD (59.8% [7.4], N = 92), compared to normal (52.1% [5.3], N = 196) eyes. Among visual functions evaluated, RMDA showed the strongest association with FD% (r = 0.35, P < 0.0001), followed by contrast sensitivity (r = -0.22, P < 0.0001). Eyes with SDD had worse FD% (58.3% [7.4], N = 87), compared to eyes without SDD (53.4% [6.0], N = 323, P = < 0.0001).<br><br>CONCLUSIONS: Choriocapillaris FD% were associated with AMD severity and with impaired vision, especially RMDA. Reduced metabolic transport and exchange across the choriocapillaris-Bruch's membrane retinal pigment epithelium (RPE) complex, a causal factor for high-risk soft drusen formation, also may impair photoreceptor sustenance from the circulation. This includes retinoid resupply, essential to dynamic rod function.},
}
@article {pmid37766772,
year = {2023},
author = {Limon, U and Gezginaslan, TA and Saygin, IO and Bozkurt, E and Kardes, E and Akcay, BIS},
title = {Efficacy of Simultaneous Application of Subretinal Tissue Plasminogen Activator and Bevacizumab for Submacular Hemorrhages.},
journal = {Beyoglu eye journal},
volume = {8},
number = {3},
pages = {198-207},
pmid = {37766772},
issn = {2587-0394},
abstract = {OBJECTIVES: The aim of the study was to evaluate the patients who received simultaneous subretinal tissue plasminogen activator (tPA) and bevacizumab for submacular hemorrhages secondary to neovascular age-related macular degeneration.<br><br>METHODS: This retrospective study included patients who underwent pars plana vitrectomy (PPV) with simultaneous subretinal tPA and subretinal bevacizumab with 18% SF6 tamponade. Anatomical and functional results of the patients before surgery and at the 1[st], 6[th], and 12[th] months after surgery, additional treatments, and complications after PPV were evaluated.<br><br>RESULTS: Eight eyes of eight patients were included in the study. The mean age of the patients was 72.38&#xb1;92.3. The mean time from the onset of symptoms to treatment was 5.13&#xb1;1.88 days. The patients' mean best-corrected visual acuity (BCVA) was 2.23&#xb1;0.14 logMAR at baseline. Mean BCVA increased significantly at 1[st], 6[th], and 12[th] months to 1.68&#xb1;0.47 logMAR, 1.58&#xb1;0.49 logMAR, and 1.51&#xb1;0.58 logMAR, respectively (p=0.001 at all). The mean central foveal thickness (CFT) in measurable patients was 836.8&#xb1;627.02 &#x3bc;m at baseline. Mean CFT decreased significantly to 370.13&#xb1;66.13 &#x3bc;m in the 1[st] month, 373.38&#xb1;78.33 &#x3bc;m in the 6th month, and 367.75&#xb1;116.43 &#x3bc;m in the 12[th] month (p<0.05). The maximum measurable subretinal hemorrhage height at baseline was 814.2&#xb1;556.45 &#x3bc;m. The mean number of anti-VEGFs performed for 12 months after surgery was 4.13&#xb1;2.1. At month 12, the ellipsoid zone could not be detected in 6 (75%) patients.<br><br>CONCLUSION: Administration of subretinal bevacizumab and subretinal tPA effectively removes subretinal hemorrhage under the fovea. Intravitreal anti-VEGF treatment must be continued, as choroidal neovascular membrane activity continues after surgery.},
}
@article {pmid37761846,
year = {2023},
author = {Wąsowska, A and Sendecki, A and Boguszewska-Chachulska, A and Teper, S},
title = {Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration.},
journal = {Genes},
volume = {14},
number = {9},
pages = {},
pmid = {37761846},
issn = {2073-4425},
mesh = {Humans ; Retinal Pigment Epithelium ; *Macular Degeneration/genetics ; *Retinal Detachment/genetics ; Risk Factors ; Bestrophins ; },
abstract = {A subset of ophthalmic imaging examination results from 334 patients were subjected to reanalysis to identify a specific group of patients with pigment epithelial detachment (PED) in at least one eye. Overall, we found a subgroup of 47 patients manifesting PED and studied their genotypes in comparison to those of patients with age-related macular degeneration without PED and healthy controls. We established a polygenic risk score that allowed the explanation of 16.3% of the variation within the disease. The highest predictive value was achieved for a model consisting of six non-coding variants: rs760306 (BEST1), rs148662546 (BEST1), rs11569560 (C3), rs74600252 (GUCA1B), rs2240688 (PROM1), and rs185507582 (TCF4). The risk of PED occurrence was found to be the highest in the first tercile, showing a 7.89-fold higher risk compared to the third tercile for AMD without PED (95% CI: 2.87; 21.71, p < 0.001) and a 7.22-fold higher risk compared to the healthy controls (95% CI: 2.60; 20.06, p < 0.001). In addition, we focused on rare variants in targeted genes. The rare variants' burden was compared among the groups, but no statistical significance was observed in the number of rare variants, predicted functional effects, or pathogenicity classification.},
}
@article {pmid37761333,
year = {2023},
author = {Interlenghi, M and Sborgia, G and Venturi, A and Sardone, R and Pastore, V and Boscia, G and Landini, L and Scotti, G and Niro, A and Moscara, F and Bandi, L and Salvatore, C and Castiglioni, I},
title = {A Radiomic-Based Machine Learning System to Diagnose Age-Related Macular Degeneration from Ultra-Widefield Fundus Retinography.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {18},
pages = {},
pmid = {37761333},
issn = {2075-4418},
abstract = {The present study was conducted to investigate the potential of radiomics to develop an explainable AI-based system to be applied to ultra-widefield fundus retinographies (UWF-FRTs) with the objective of predicting the presence of the early signs of Age-related Macular Degeneration (AMD) and stratifying subjects with low- versus high-risk of AMD. The ultimate aim was to provide clinicians with an automatic classifier and a signature of objective quantitative image biomarkers of AMD. The use of Machine Learning (ML) and radiomics was based on intensity and texture analysis in the macular region, detected by a Deep Learning (DL)-based macular detector. Two-hundred and twenty six UWF-FRTs were retrospectively collected from two centres and manually annotated to train and test the algorithms. Notably, the combination of the ML-based radiomics model and the DL-based macular detector reported 93% sensitivity and 74% specificity when applied to the data of the centre used for external testing, capturing explainable features associated with drusen or pigmentary abnormalities. In comparison to the human operator's annotations, the system yielded a 0.79 Cohen κ, demonstrating substantial concordance. To our knowledge, these results are the first provided by a radiomic approach for AMD supporting the suitability of an explainable feature extraction method combined with ML for UWF-FRT.},
}
@article {pmid37760886,
year = {2023},
author = {Salas, A and Badia, A and Fontrodona, L and Zapata, M and García-Arumí, J and Duarri, A},
title = {Neovascular Progression and Retinal Dysfunction in the Laser-Induced Choroidal Neovascularization Mouse Model.},
journal = {Biomedicines},
volume = {11},
number = {9},
pages = {},
pmid = {37760886},
issn = {2227-9059},
support = {PI13/0096//Instituto de Salud Carlos III/ ; PI18/00219//Instituto de Salud Carlos III/ ; PhD fellowship//Fundaci&#xf3; Josep Palau Franc&#xe0;s/ ; },
abstract = {The mouse model of laser-induced choroidal neovascularization (LI-CNV) has been widely used to study neovascular age-related macular degeneration; however, it still lacks a comprehensive characterization. Here, CNV was induced in the eyes of 12-week-old C57BL/6J male mice by argon laser irradiation. We studied the CNV lesion progression of an LI-CNV mouse cohort by using multimodal imaging (color fundus, optical coherence tomography (OCT), and fluorescence angiography, focal electroretinography features for 14 days, and related cytokines, angiogenic factors, and reactive gliosis for 5 days. CNV lesions involving the rupture of the Bruch's membrane were confirmed using funduscopy and OCT after laser photocoagulation. During the initial stage, from the CNV induction until day 7, CNV lesions presented leakage observed by using fluorescence angiography and a typical hyperreflective area with cell infiltration, subretinal leakage, and degeneration of photoreceptors observed through OCT. This correlated with decreased retinal responses to light. Moreover, inflammatory and angiogenic markers were reduced to basal levels in the first 5 days of CNV progression. In contrast, reactive gliosis and the VEGF expression in retinal sections were sustained, with infiltration of endothelial cells in the subretinal space. In the second stage, between days 7 and 14 post-induction, we observed stabilization of the CNV lesions, a hyperfluorescent area corresponding to the formation of fibrosis, and a partial rescue of retinal function. These findings suggest that the LI-CNV lesion development goes through an acute phase during the first seven days following induction, and then the CNV lesion stabilizes. According to these results, this model is suitable for screening anti-inflammatory and anti-angiogenic drugs in the early stages of LI-CNV. At the same time, it is more convenient for screening anti-fibrotic compounds in the later stages.},
}
@article {pmid37758754,
year = {2023},
author = {Araújo, T and Aresta, G and Schmidt-Erfurth, U and Bogunović, H},
title = {Few-shot out-of-distribution detection for automated screening in retinal OCT images using deep learning.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {16231},
pmid = {37758754},
issn = {2045-2322},
mesh = {Humans ; Tomography, Optical Coherence ; *Deep Learning ; Reproducibility of Results ; Area Under Curve ; Behavior Therapy ; *Macular Degeneration/diagnostic imaging ; },
abstract = {Deep neural networks have been increasingly proposed for automated screening and diagnosis of retinal diseases from optical coherence tomography (OCT), but often provide high-confidence predictions on out-of-distribution (OOD) cases, compromising their clinical usage. With this in mind, we performed an in-depth comparative analysis of the state-of-the-art uncertainty estimation methods for OOD detection in retinal OCT imaging. The analysis was performed within the use-case of automated screening and staging of age-related macular degeneration (AMD), one of the leading causes of blindness worldwide, where we achieved a macro-average area under the curve (AUC) of 0.981 for AMD classification. We focus on a few-shot Outlier Exposure (OE) method and the detection of near-OOD cases that share pathomorphological characteristics with the inlier AMD classes. Scoring the OOD case based on the Cosine distance in the feature space from the penultimate network layer proved to be a robust approach for OOD detection, especially in combination with the OE. Using Cosine distance and only 8 outliers exposed per class, we were able to improve the near-OOD detection performance of the OE with Reject Bucket method by [Formula: see text] 10% compared to without OE, reaching an AUC of 0.937. The Cosine distance served as a robust metric for OOD detection of both known and unknown classes and should thus be considered as an alternative to the reject bucket class probability in OE approaches, especially in the few-shot scenario. The inclusion of these methodologies did not come at the expense of classification performance, and can substantially improve the reliability and trustworthiness of the resulting deep learning-based diagnostic systems in the context of retinal OCT.},
}
@article {pmid37758543,
year = {2023},
author = {Merle, B},
title = {[Nutrition and age-related macular degeneration].},
journal = {Journal francais d'ophtalmologie},
volume = {46},
number = {8},
pages = {949-955},
doi = {10.1016/j.jfo.2023.09.002},
pmid = {37758543},
issn = {1773-0597},
mesh = {Humans ; Aged, 80 and over ; *Dietary Supplements ; Vitamins ; *Macular Degeneration/epidemiology/etiology/prevention &amp; control ; Antioxidants/therapeutic use ; Micronutrients ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in France and in other industrialized countries. AMD affects around 20 % of the population over the age of 80 years. This complex and multifactorial disease involves both genetic susceptibility and environmental factors. Smoking and nutrition are well-known modifiable risk factors for AMD. Numerous studies provide convincing arguments in favor of micronutrients to encourage dietary advice and the prescription of nutritional supplements containing antioxidant vitamins, lutein and omega-3 fatty acids. Attention to modifiable risk factors is of utmost importance to reduce progression to advanced AMD and associated medical and societal burdens.},
}
@article {pmid37757996,
year = {2024},
author = {Greferath, U and Fletcher, E and Savige, J and Mack, HG},
title = {Drusen and Other Retinal Findings in People With IgA Glomerulonephritis.},
journal = {American journal of ophthalmology},
volume = {257},
number = {},
pages = {247-253},
doi = {10.1016/j.ajo.2023.09.019},
pmid = {37757996},
issn = {1879-1891},
mesh = {Humans ; Male ; Female ; *Retinal Drusen/diagnosis/pathology ; *Glomerulonephritis, IGA/complications/diagnosis ; Vitronectin ; *Macular Degeneration/pathology ; *Renal Insufficiency ; Immunoglobulin A ; },
abstract = {PURPOSE: Retinal drusen have been described in people with IgA nephropathy. We examined the frequency of drusen in IgA nephropathy and compared their location and composition with those for drusen in age-related macular degeneration.<br><br>DESIGN: Immunohistological case series of eyes of patients with IgA nephropathy, and a comparison eye with age-related macular degeneration.<br><br>METHODS: Donor eyes from 4 individuals (3 male, 1 female, aged 40-80 years) with biopsy-proven IgA nephropathy and kidney failure were examined for the presence of drusen, and location and composition using antibodies for vitronectin, IgA, IgM, IgG, C3, and C1q. Results were compared with those for drusen in macular degeneration without IgA nephropathy.<br><br>RESULTS: All 4 donors had sparse, subretinal pigment epithelium drusen of 55-65 mm diameter that stained for vitronectin but not for IgA or complement. All donors had retinal capillaries and choriocapillaris staining for IgA. The youngest donor (female, 40) had rare deposits in the outer nuclear layer that stained for IgA, but not for vitronectin. The oldest donor (male, 82) had large cystlike spaces in the inner nuclear and plexiform layers, and smaller cysts in the outer nuclear layer, with no staining for IgA or complement.<br><br>CONCLUSIONS: Retinal drusen are uncommon in IgA nephropathy, even with kidney failure. Drusen in IgA nephropathy resemble drusen found in age-related macular degeneration. IgA-staining deposits in the outer nuclear layer were likely due to systemic deposition of IgA and complement activation. The nature of cystic spaces is unknown. Further analysis of the retinas of people with glomerulonephritis is recommended.},
}
@article {pmid37756667,
year = {2024},
author = {Meer, EA and Targ, S and Zhang, N and Hoggatt, KJ and Mehta, KM and Brodie, F},
title = {AGE-RELATED MACULAR DEGENERATION INJECTION FREQUENCY: Effects of Distance Traveled and Travel Support.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {2},
pages = {230-236},
pmid = {37756667},
issn = {1539-2864},
mesh = {Humans ; *Angiogenesis Inhibitors ; Endothelial Growth Factors ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Travel ; Retrospective Studies ; },
abstract = {PURPOSE: Although efficacious, intravitreal anti-vascular endothelial growth factor therapy regimens for neovascular age-related macular degeneration can prove difficult for patients to adhere to because of high cost and burden of transportation.<br><br>METHODS: Analysis of electronic health record data from the San Francisco Veterans Administration Medical Center eye clinic (January 1, 2010 to December 31, 2019) was performed, extracting demographic data, anti-vascular endothelial growth factor injection history, and enrollment in the SFVA travel benefit program. Two-tailed P -values were calculated for Poisson regression examining average number of injections per year as the outcome and distance traveled as the primary predictor. Travel benefit was evaluated as a modifying effect on the distance-injection relationship.<br><br>RESULTS: Three hundred and eighteen patients who received intravitreal injection for treatment of neovascular age-related macular degeneration were included in the analysis. Median (interquartile range) distance to clinic was 31.5 miles (7.4-69.4 miles). Driving distance in miles was inversely associated with average number of injections per year. Among all 318 patients, for every additional 100 miles a patient lived from our clinic, the patient received on average 2.5 fewer injections per year (distance = -0.0025, P < 0.001), but this was not the case for patients with travel benefits (distance = -0.0011, P = 0.362).<br><br>CONCLUSION: The greater the distance from a patient's eye clinic, the lower the average number of injections per year. However, travel benefits mitigated this relationship, highlighting opportunities for improving patient's adherence through assistance programs.},
}
@article {pmid37756354,
year = {2023},
author = {Thompson, AC and Johnson, E and Miller, ME and Williamson, JD and Newman, AB and Cummings, S and Cawthon, P and Kritchevsky, SB},
title = {The relationship between visual function and physical performance in the Study of Muscle, Mobility and Aging (SOMMA).},
journal = {PloS one},
volume = {18},
number = {9},
pages = {e0292079},
pmid = {37756354},
issn = {1932-6203},
support = {R01 AG059416/AG/NIA NIH HHS/United States ; P30 AG024827/AG/NIA NIH HHS/United States ; K23 EY030897/EY/NEI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; P30 AG021332/AG/NIA NIH HHS/United States ; },
mesh = {Female ; Humans ; Aged ; Aged, 80 and over ; Male ; Cross-Sectional Studies ; *Muscles ; Visual Acuity ; Aging ; *Macular Degeneration ; },
abstract = {PURPOSE: The relationship of types of visual function to different aspects of physical function, especially strength and coordination, has been understudied, but delineation of these relationships could suggest potentially modifiable targets prior to the onset of disability.<br><br>METHODS: Cross-sectional analysis of visual function (self-reported eyesight and eye disease, visual acuity, contrast sensitivity) and physical function tests in 877 older adults (mean age 76.36&#xb1;5.01 years, 59.2% women, and 13.3% Black race). Separate linear regression models were constructed for short physical performance battery (SPPB), expanded SPPB (eSPPB), their components (gait speed, chair stand, balance, narrow walk), stair climb, four-square step, leg extension peak power and strength, and grip strength.<br><br>RESULTS: In adjusted models, worse acuity, worse contrast sensitivity, and self-reported poor vision were significantly associated with worse performance on the eSPPB and four-square step test. Worse contrast sensitivity, but not acuity, was significantly associated with shorter balance times, slower chair stand pace, longer stair climb time, and worse SPPB score. Associations of worse acuity and contrast sensitivity with weaker leg extension power, leg strength, and grip strength were attenuated by covariate adjustment. Self-reported macular degeneration, but not cataract or glaucoma, was associated with worse performance on SPPB, eSPPB, balance, stair climb, and four-square step tests in adjusted models. Worse contrast sensitivity and macular degeneration remained associated with worse SPPB and balance after controlling for visual acuity and self-reported eyesight.<br><br>CONCLUSIONS: Poor contrast sensitivity was more strongly associated with worse physical performance than acuity, especially for complex tasks that dynamically challenge coordination and balance. Future studies should examine if older adults with contrast sensitivity impairment would benefit from targeted intervention to decrease their risk of disability.},
}
@article {pmid37755161,
year = {2023},
author = {Sluijter, ME and Teixeira, A and Vissers, K and Brasil, LJ and van Duijn, B},
title = {The Anti-Inflammatory Action of Pulsed Radiofrequency-A Hypothesis and Potential Applications.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {11},
number = {3},
pages = {},
pmid = {37755161},
issn = {2076-3271},
mesh = {Humans ; Animals ; Rats ; *Chronic Pain/therapy ; *Pulsed Radiofrequency Treatment ; Anti-Inflammatory Agents ; Inflammation/therapy ; *Medicine ; },
abstract = {In 2013, it was reported that pulsed radiofrequency (PRF) could be applied to obtain a systemic anti-inflammatory effect. Patients with chronic pain and patients with an inflammatory condition from other disciplines could potentially profit from this finding. At that time, intravenous application was used, but since then, it became clear that it could be applied transcutaneously as well. This procedure was named RedoxPRF. This can be used both for regional and for systemic application. Recently, the basic element of the mode of action has been clarified from the analysis of the effects of PRF on a standard model of muscle injury in rats. The objective of this paper is to present a hypothesis on the mode of action of RedoxPRF now that the basic mechanism has become known. Cell stress causes an increased production of free radicals, disturbing the redox equilibrium, causing oxidative stress (OS) either directly or secondarily by other types of stress. Eventually, OS causes inflammation and an increased sympathetic (nervous) system activity. In the acute form, this leads to immune paralysis; in the chronic form, to immune tolerance and chronic inflammation. It is hypothesized that RedoxPRF causes a reduction of free radicals by a recombination of radical pairs. For systemic application, the target cells are the intravascular immune cells that pass through an activated area as on an assembly line. Hypothesis conclusions: 1. RedoxPRF treatment works selectively on OS. It has the unique position of having a point of engagement at the most upstream level of the train of events. 2. RedoxPRF has the potential of being a useful tool in the treatment of inflammatory diseases and possibly of stage 4 cancer. 3. In the treatment of chronic pain, RedoxPRF is an entirely new method because it is different from ablation as well as from stimulation. We propose the term "functional restoration". 4. Controlled studies must be conducted to develop this promising new field in medicine further.},
}
@article {pmid37753246,
year = {2023},
author = {Saba, NJ and Walter, SD},
title = {Efficacy, Safety, and Durability of Brolucizumab: An 8-Month Post-Marketing Surveillance Analysis.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {2791-2802},
pmid = {37753246},
issn = {1177-5467},
abstract = {IMPORTANCE: Brolucizumab (Beovu[®]) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns.<br><br>OBJECTIVE: We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world.<br><br>This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020.<br><br>MAIN OUTCOMES AND MEASURES: Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events.<br><br>RESULTS: The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-na&#xef;ve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001).<br><br>CONCLUSIONS AND RELEVANCE: Brolucizumab treatment was associated with VA improvement in na&#xef;ve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee's analysis of HAWK and HARRIER.},
}
@article {pmid37752703,
year = {2023},
author = {Ke, X and Jiang, H and Li, Q and Luo, S and Qin, Y and Li, J and Xie, Q and Zheng, Q},
title = {Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {31},
number = {11},
pages = {3308-3321},
pmid = {37752703},
issn = {1525-0024},
mesh = {Animals ; Humans ; Vascular Endothelial Growth Factor A/metabolism ; Retina/metabolism ; *Choroidal Neovascularization/genetics/therapy ; Primates/genetics/metabolism ; Intravitreal Injections ; RNA ; *Macular Degeneration/pathology ; Genetic Therapy/methods ; Angiogenesis Inhibitors/pharmacology ; Recombinant Fusion Proteins ; },
abstract = {The upregulation of vascular endothelial growth factor (VEGF) is strongly associated with the development of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD). Currently, the standard treatment for nAMD involves frequent intravitreal injections of anti-VEGF agents, which inhibit the growth of new blood vessels and prevent leakage. However, this treatment regimen places a significant burden on patients, their families, and healthcare providers due to the need for repeated visits to the clinic for injections. Gene therapy, which enables the sustained expression of anti-VEGF proteins after a single injection, can dramatically reduce the treatment burden. KH631 is a recombinant adeno-associated virus 8 vector that encodes a human VEGF receptor fusion protein, and it is being developed as a long-term treatment for nAMD. In preclinical studies using non-human primates, subretinal administration of KH631 at a low dose of 3 × 10[8] vg/eye resulted in remarkable retention of the transgene product in the retina and prevented the formation and progression of grade IV CNV lesions. Furthermore, sustained transgene expression was observed for more than 96 weeks. These findings suggest that a single subretinal injection of KH631 has the potential to offer a one-time, low-dose treatment for nAMD patients.},
}
@article {pmid37750953,
year = {2024},
author = {Maruyama-Inoue, M and Yanagi, Y and Inoue, T and Kadonosono, K},
title = {Comparison of functional and morphologic changes between brolucizumab and faricimab in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {2},
pages = {589-599},
pmid = {37750953},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence ; *Retinal Perforations ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/diagnosis/drug therapy ; Receptors, Vascular Endothelial Growth Factor ; *Antibodies, Bispecific ; *Antibodies, Monoclonal, Humanized ; },
abstract = {PURPOSE: This study aimed to compare functional and morphologic changes in the loading phase between patients with treatment-naïve macular neovascularization (MNV) due to neovascular age-related macular degeneration (nAMD) treated with either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting.<br><br>METHODS: We retrospectively studied 92 consecutive eyes of 90 patients with neovascular nAMD who were scheduled to receive IVBr (42 eyes of 41 patients) or IVF (50 eyes of 49 patients) injections between October 2021 and December 2022. All patients received three consecutive monthly injections of 6.0 mg/0.05 mL brolucizumab or 6.0 mg/0.05 mL faricimab. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and central choroidal thickness (CCT) at baseline and 1, 2, and 4 months after the initial treatment were measured and compared between the groups.<br><br>RESULTS: Thirty-seven eyes in IVBr group and forty-seven eyes in IVF group who finished treatments in the loading phase were assessed at the follow-up examination. The BCVA, CFT, and CCT changed significantly after loading phase in both groups (P < 0.05 for both comparisons). The IVBr group had more rapid improvement of the BCVA (P = 0.037) at 1 month than the IVF group, but there was no difference at 4 months (P = 0.367). The CFT and CCT decreases tended to be greater in the IVBr group than in the IVF group throughout the follow-up period. Of the five eyes excluded from the IVBr group, one eye (2.4%) each had intraocular inflammation (IOI) and was a non-responder, and two eyes (4.8%) had retinal pigment epithelial tears after treatment. Of the three eyes excluded from the IVF group, two eyes (4.0%) did not respond to the treatment.<br><br>CONCLUSIONS: Both IVBr and IVF injections were well-tolerated and improved the VA in treatment-na&#xef;ve patients with MNV due to nAMD after a loading phase, although IVBr caused a trend toward&#xa0;faster visual improvements in the BCVA. The IVBr group also had greater reductions of the CFT and CCT than the IVF group. However, the potential for adverse events and no response to treatment with each drug are considerations.},
}
@article {pmid37749706,
year = {2023},
author = {Fortes, BH and Fairbanks, AM and Nirmalan, AA and Hodge, DO and Ferenchak, K and Barkmeier, AJ},
title = {Diurnal variation of optical coherence tomography-based macular fluid in exudative age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {57},
pmid = {37749706},
issn = {2056-9920},
support = {vitreoretinal surgery foundation//vitreoretinal surgery foundation/ ; },
abstract = {BACKGROUND: Significant diurnal fluctuation of optical coherence tomography (OCT)-based macular fluid occurs in patients with several macular conditions including diabetic macular edema (DME) and cystoid macular edema due to retinal venous occlusion (RVO). OCT imaging and analysis of macular fluid status plays a central role in clinical management of exudative age-related macular degeneration (eAMD), however diurnal variation of eAMD OCT findings has not yet been formally studied. Herein, we investigate whether clinically meaningful fluctuation of OCT-based macular fluid occurs in patients with eAMD.<br><br>METHODS: Prospective observational study. Patients with eAMD and intra- and/or sub-retinal fluid on early AM OCT were enrolled to receive two consecutive OCT scans at least four hours later. Retinal layers were manually segmented on all OCT rasters and AM-to-PM and PM-to-PM image pairs were analyzed for total retinal and neurosensory retinal volume changes within the central 1 and 3&#xa0;mm ETDRS subfields. Finally, two masked retinal specialists analyzed all OCT image pairs for qualitative differences that may impact clinical management.<br><br>RESULTS: 21 patients with eAMD and fluid on OCT were recruited between January 2020 and November 2021. There was no mean difference between AM and PM central 3&#xa0;mm total retinal volume (p&#x2009;=&#x2009;0.56), central 3&#xa0;mm neurosensory retinal volume (p&#x2009;=&#x2009;0.25), central 1&#xa0;mm total retinal mean thickness (p&#x2009;=&#x2009;0.96), or central 1&#xa0;mm neurosensory retinal mean thickness (p&#x2009;=&#x2009;0.63), nor were any differences identified in PM-to-PM control comparisons. Qualitative analysis by two masked experts identified no clinically significant differences between any AM-to-PM OCT image pairs.<br><br>CONCLUSIONS: No significant diurnal variation in OCT-based macular fluid or thickness was identified in patients with eAMD, either quantitatively or qualitatively.},
}
@article {pmid37748684,
year = {2023},
author = {Fernández-Vigo, JI and Blanco-Darriba, D and Etxabe-Avila, H and Montolío-Marzo, E and Robles-Amor, P and Escobar-Moreno, MJ and Burgos-Blasco, B},
title = {Comparative analysis of the quality of life among different retinal diseases.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {98},
number = {11},
pages = {633-639},
doi = {10.1016/j.oftale.2023.07.007},
pmid = {37748684},
issn = {2173-5794},
mesh = {Humans ; *Macular Edema/etiology ; *Diabetic Retinopathy ; Quality of Life ; *Macular Degeneration/psychology ; Cross-Sectional Studies ; *Retinal Diseases ; *Retinal Vein Occlusion ; Vision Disorders ; },
abstract = {PURPOSE: To assess the impact on the quality of life (QoL) among different retinal diseases such as diabetic macular edema (DME), retinal vein occlusion (RVO), pathologic myopia (PM), neovascular age-related macular degeneration (nAMD) and central serous chorioretinopathy (CSC).<br><br>METHODS: A cross-sectional study was carried out in 241 patients, affected by DME (n=44), RVO (n=41), PM (n=34) and nAMD (n=85) receiving intravitreal injections due to the presence of macular edema or choroidal neovascularization. The CSC patients included (n=37) were candidates for laser treatment. The patients included completed the National Eye Visual Functioning Questioning-25 (NEI VFQ-25). Best eye visual acuity (BEVA) was recorded using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale.<br><br>RESULTS: There were significant differences between subgroups for all the domains, except for the general vision in which all scores among diseases ranged from 40.7 to 45.2 out of 100 (P=.436), despite the difference in BEVA (CSC: 86.3&#xb1;11.9; RVO: 78.5&#xb1;15.5, DME: 73.3&#xb1;15.2, nAMD: 72.9&#xb1;12.6 and PM: 68.5&#xb1;18.1 letters respectively; P<.001). The lowest VFQ-25 total score was observed in the PM patients (52.1&#xb1;20.9), followed by nAMD (55.3&#xb1;20.8), RVO (65.0&#xb1;22.3), DME (68.6&#xb1;21.0) and CSC (70.9&#xb1;16.2). The DME group reported the worst score for general health (38.9&#xb1;21.4). Mental health and role difficulties were lowest for PM (48.2&#xb1;28.8 and 48.2&#xb1;31.9, P<.007).<br><br>CONCLUSIONS: This study reveals the differences in the QoL among DME, RVO, nAMD, PM and CSC, describing the different repercussions that they can suffer, observing a higher impact in PM and nAMD.},
}
@article {pmid37747440,
year = {2024},
author = {Zhang, X and Zhuang, X and Dong, J and Fu, B and Zhang, G and Xu, L},
title = {Clinical efficacy of conbercept injection on neovascular age-related macular degeneration under different levels of inflammation.},
journal = {Advances in clinical and experimental medicine : official organ Wroclaw Medical University},
volume = {33},
number = {4},
pages = {335-342},
doi = {10.17219/acem/168808},
pmid = {37747440},
issn = {1899-5276},
mesh = {Humans ; Male ; *Recombinant Fusion Proteins/administration &amp; dosage/adverse effects ; Female ; Aged ; *Intravitreal Injections ; *Inflammation/drug therapy ; *Macular Degeneration/drug therapy ; Treatment Outcome ; Aged, 80 and over ; Visual Acuity/drug effects ; Choroidal Neovascularization/drug therapy ; C-Reactive Protein/analysis/metabolism ; Middle Aged ; Angiogenesis Inhibitors/administration &amp; dosage/adverse effects ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is considered one of the most common causes of irreversible blindness among elderly patients. Neovascular AMD, which accounts for 10% of all AMD cases, can cause devastating vision loss due to choroidal neovascularization (CNV). The clinical effects and safety of intravitreal injection of conbercept in patients suffering from neovascular AMD have not been fully evaluated.<br><br>OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of intravitreal injection of conbercept in patients with neovascular AMD with different levels of inflammation.<br><br>MATERIAL AND METHODS: A total of 120 consecutive patients with neovascular AMD who underwent intravitreal injection of conbercept (3 injections per month + pro re nata (3 + PRN)) were included and stratified based on the intraocular level of high-sensitivity C-reactive protein (hs-CRP). The level of inflammation was defined as low, medium or high, based on the concentration of hs-CRP prior to injection. Before and after conbercept injections, best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared, respectively. Moreover, cytokine markers as well as the frequency of injections and adverse events (AEs) were measured.<br><br>RESULTS: There were significant differences in BCVA and CRT between low, medium and high tertiles. Compared to the baseline, improved BCVA was observed, and CRT declined significantly after operation. Adverse events were most observed in high tertiles. A significant decrease in vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8 was observed after 1 year.<br><br>CONCLUSIONS: The effectiveness of conbercept on neovascular AMD varies depending on the level of inflammation, which could be achieved by administering different injection frequencies at different levels of inflammation. Furthermore, conbercept is associated with the reduction of inflammatory factor (IL-6 and IL-8) levels after intravitreal injection, which suggests that suppressing inflammatory response might contribute to the clinical efficacy of anti-VEGF treatment. Our results provide a novel mechanism for conbercept in patients with neovascular AMD.},
}
@article {pmid37746139,
year = {2023},
author = {Wu, W and Li, Y and Hu, T and Tao, W and Wen, D and Lei, H},
title = {Editorial: Ocular neurodegenerative diseases: novel mechanisms, diagnosis, and therapeutic strategies.},
journal = {Frontiers in neuroscience},
volume = {17},
number = {},
pages = {1274778},
doi = {10.3389/fnins.2023.1274778},
pmid = {37746139},
issn = {1662-4548},
}
@article {pmid37746113,
year = {2023},
author = {Panos, GD and Lakshmanan, A and Dadoukis, P and Ripa, M and Motta, L and Amoaku, WM},
title = {Faricimab: Transforming the Future of Macular Diseases Treatment - A Comprehensive Review of Clinical Studies.},
journal = {Drug design, development and therapy},
volume = {17},
number = {},
pages = {2861-2873},
pmid = {37746113},
issn = {1177-8881},
mesh = {Humans ; Vascular Endothelial Growth Factor A ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; *Macular Edema/drug therapy ; *Diabetic Retinopathy/drug therapy ; Intravitreal Injections ; },
abstract = {Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab's application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases.},
}
@article {pmid37745353,
year = {2023},
author = {Fasih-Ahmad, S and Wang, Z and Mishra, Z and Vatanatham, C and Clark, ME and Swain, TA and Curcio, CA and Owsley, C and Sadda, SR and Hu, ZJ},
title = {Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.09.10.23295309},
pmid = {37745353},
abstract = {PURPOSE: While intermediate and late age-Related Macular Degeneration (AMD) have been widely investigated, rare studies were focused on the pathophysiologic mechanism of early AMD. Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The status of outer retinal bands on optical coherence tomography (OCT) may be potential imaging biomarkers and the purpose is to investigate the hypothesis that the integrity of interdigitation zone (IZ) may provide insight into the health of photoreceptors and retinal pigment epithelium (RPE) in early AMD.<br><br>METHODS: We establish the structure-function relationship between ellipsoid zone (EZ) integrity and RMDA, and IZ integrity and RMDA in a large-scale OCT dataset from eyes with normal aging (n=237), early AMD (n=138), and intermediate AMD (n=101) by utilizing a novel deep-learning-derived algorithm with manual correction when needed to segment the EZ and IZ on OCT B-scans (57,596 B-scans), and utilizing the AdaptDx device to measure RMDA.<br><br>RESULTS: Our data demonstrates that slower RMDA is associated with less preserved EZ (r = -0.334; p<0.001) and IZ area (r = -0.591; p<0.001), and decreased IZ thickness (r = -0.434; p<0.001). These associations are not apparent when considering normal eyes alone.<br><br>CONCLUSIONS: The association with IZ area and RMDA in large-scale data is biologically plausible because retinoid availability and transfer at the interface attributed to IZ is rate-limiting for RMDA. This study supports the hypothesis that the IZ integrity provides insight into the health of photoreceptors and RPE in early AMD and is a potential new imaging biomarker.},
}
@article {pmid37745288,
year = {2023},
author = {Sammons, E and Bowman, L and Stevens, W and Buck, G and Wallendszus, K and Hammami, I and Parish, S and Armitage, J and , },
title = {ASCEND-Eye: Rationale, design and baseline characteristics for a sub-study of the ASCEND randomised trial, exploring the effects of aspirin and omega-3 fatty acids on diabetic retinopathy and age-related macular degeneration.},
journal = {Contemporary clinical trials communications},
volume = {35},
number = {},
pages = {101184},
pmid = {37745288},
issn = {2451-8654},
support = {CH/1996001/9454/BHF_/British Heart Foundation/United Kingdom ; MC_UU_00017/5/MRC_/Medical Research Council/United Kingdom ; SP/08/010/25939/BHF_/British Heart Foundation/United Kingdom ; MC_UU_12026/5/MRC_/Medical Research Council/United Kingdom ; SP/14/3/31114/BHF_/British Heart Foundation/United Kingdom ; MC_UU_00017/3/MRC_/Medical Research Council/United Kingdom ; },
abstract = {BACKGROUND: Aspirin and omega-3 fatty acids (FAs) have potential disease-modifying roles in diabetic retinopathy (DR) and age-related macular degeneration (AMD), but randomized evidence of these effects is limited. We present the rationale and baseline characteristics of ASCEND-Eye, a sub-study of the double-blind, 2x2 factorial design, randomized placebo-controlled ASCEND (A Study of Cardiovascular Events iN Diabetes) trial of 100 mg aspirin daily and, separately, 1g omega-3 FAs daily for the primary prevention of serious cardiovascular events, in 15,480 British adults, aged 40 years or older with diabetes.<br><br>METHODS: Eye events will be derived from three sources: 1) participant follow-up questionnaires from ASCEND, 2) electronic NHS Diabetic Eye Screening Programme (DESP) data and 3) responses to the National Eye Institute's Visual Function Questionnaire-25 (NEI-VFQ-25) sent to a subset of participants after the main trial ended. Analytic cohorts and outcomes relevant to these data sources are described. The primary outcome is referable diabetic eye disease, a secondary outcome is incident AMD events.<br><br>RESULTS: Participant-reported events were ascertained for the full cohort of randomized individuals who were followed up over 7.4 years in ASCEND (n&#xa0;=&#xa0;15,480). Linked DESP data were available for 48% of those (n&#xa0;=&#xa0;7360), and 57% completed the NEI-VFQ-25 (n&#xa0;=&#xa0;8839). The baseline characteristics of these three cohorts are presented.<br><br>DISCUSSION: Establishing the risks and benefits of drugs commonly taken by people with diabetes, the elderly, or both, and finding new treatments for DR and AMD is important. ASCEND-Eye provides the opportunity to evaluate the effect of aspirin and, separately, omega-3 FAs for both conditions.<br><br>STUDY REGISTRATION: Eudract No. 2004-000991-15; Multicentre Research Ethics Committee Ref No. 03/8/087; ClinicalTrials.gov No. NCT00135226; ISRCTN No. ISRCTN60635500.},
}
@article {pmid37741821,
year = {2023},
author = {Gonzalez Calle, A and Paknahad, J and Pollalis, D and Kosta, P and Thomas, B and Tew, BY and Salhia, B and Louie, S and Lazzi, G and Humayun, M},
title = {An extraocular electrical stimulation approach to slow down the progression of retinal degeneration in an animal model.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {15924},
pmid = {37741821},
issn = {2045-2322},
mesh = {Humans ; Animals ; *Retinal Degeneration/therapy ; Retina ; *Macular Degeneration ; Models, Animal ; Electric Stimulation ; },
abstract = {Retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are characterized by unrelenting neuronal death. However, electrical stimulation has been shown to induce neuroprotective changes in the retina capable of slowing down the progression of retinal blindness. In this work, a multi-scale computational model and modeling platform were used to design electrical stimulation strategies to better target the bipolar cells (BCs), that along with photoreceptors are affected at the early stage of retinal degenerative diseases. Our computational findings revealed that biphasic stimulus pulses of long pulse duration could decrease the activation threshold of BCs, and the differential stimulus threshold between ganglion cells (RGCs) and BCs, offering the potential of targeting the BCs during the early phase of degeneration. In vivo experiments were performed to evaluate the electrode placement and parameters found to target bipolar cells and evaluate the safety and efficacy of the treatment. Results indicate that the proposed transcorneal Electrical Stimulation (TES) strategy can attenuate retinal degeneration in a Royal College of Surgeon (RCS) rodent model, offering the potential to translate this work to clinical practice.},
}
@article {pmid37741457,
year = {2023},
author = {Zhu, S and Xu, R and Engel, AL and Wang, Y and McNeel, R and Hurley, JB and Chao, JR and Du, J},
title = {Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina.},
journal = {The Journal of biological chemistry},
volume = {299},
number = {11},
pages = {105275},
pmid = {37741457},
issn = {1083-351X},
support = {R01 EY034364/EY/NEI NIH HHS/United States ; P20 GM144230/GM/NIGMS NIH HHS/United States ; R01 EY032462/EY/NEI NIH HHS/United States ; P20 GM103434/GM/NIGMS NIH HHS/United States ; R24 HD000836/HD/NICHD NIH HHS/United States ; R01 EY031324/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; *Amino Acids/metabolism ; Aspartic Acid/metabolism ; Glutamates/metabolism ; Glutamine/metabolism ; Nitrogen/metabolism ; Proline/metabolism ; Proline Oxidase/metabolism ; Retina/metabolism ; *Retinal Pigment Epithelium/metabolism ; },
abstract = {It is known that metabolic defects in the retinal pigment epithelium (RPE) can cause degeneration of its neighboring photoreceptors in the retina, leading to retinal degenerative diseases such as age-related macular degeneration. However, how RPE metabolism supports the health of the neural retina remains unclear. The retina requires exogenous nitrogen sources for protein synthesis, neurotransmission, and energy metabolism. Using [15]N tracing coupled with mass spectrometry, we found human RPE can utilize the nitrogen in proline to produce and export 13 amino acids, including glutamate, aspartate, glutamine, alanine, and serine. Similarly, we found this proline nitrogen utilization in the mouse RPE/choroid but not in the neural retina of explant cultures. Coculture of human RPE with the retina showed that the retina can take up the amino acids, especially glutamate, aspartate, and glutamine, generated from proline nitrogen in the RPE. Intravenous delivery of [15]N proline in vivo demonstrated [15]N-derived amino acids appear earlier in the RPE before the retina. We also found proline dehydrogenase, the key enzyme in proline catabolism is highly enriched in the RPE but not the retina. The deletion of proline dehydrogenase blocks proline nitrogen utilization in RPE and the import of proline nitrogen-derived amino acids in the retina. Our findings highlight the importance of RPE metabolism in supporting nitrogen sources for the retina, providing insight into understanding the mechanisms of the retinal metabolic ecosystem and RPE-initiated retinal degenerative diseases.},
}
@article {pmid37739248,
year = {2023},
author = {Lee, S and Hong, HK and Song, JS and Jeong, SI and Chung, JY and Woo, SJ and Park, KD},
title = {Intravitreal injectable hydrogel rods with long-acting bevacizumab delivery to the retina.},
journal = {Acta biomaterialia},
volume = {171},
number = {},
pages = {273-288},
doi = {10.1016/j.actbio.2023.09.025},
pmid = {37739248},
issn = {1878-7568},
mesh = {Animals ; Humans ; Bevacizumab/pharmacology ; *Hydrogels/pharmacology ; Angiogenesis Inhibitors/pharmacology ; Retina ; Intravitreal Injections ; Drug Carriers/pharmacology ; *Vascular Diseases ; },
abstract = {Retinal vascular diseases such as neovascular age-related macular degeneration (nAMD) are the leading cause of blindness worldwide. They can be treated with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents by inhibiting VEGF which is a major agent of abnormal blood vessel growth. However, because of drug's short half-life, clinical treatment often requires monthly repeated intravitreal injections, causing treatment burden and undertreatment. Among various kinds of drug carriers, in situ forming hydrogels have been studied as potential intravitreal drug carriers for the high drug loading, easy injection, controlled drug release, and protection of encapsulated drugs from the environment. However, gelation time, crosslinking degree, and drug release patterns following injection of a liquid that will be subsequently gelled in situ are susceptible to be hindered by dilution of the hydrogel precursor solution with body fluids (e.g., blood or vitreous). Here, we report an injectable pre-crosslinked hydrogel rod to overcome the limitations of in situ forming hydrogels and to extend intravitreal half-life of anti-VEGF for reducing intraocular injection frequency. Hydrogel rods can be simply prepared using in situ forming hydrogels, and injectable using a designed rod injector. The adjustable crosslinking degree of hydrogel rods easily controlled bevacizumab release profiles in a sustained manner. Compared with in situ forming hydrogels, hydrogel rods effectively reduced initial burst release, and showed sustained release with long-term drug efficacy in vitro. From the 4-month in vivo pharmacokinetic analysis, following the intravitreal injection of hydrogel rods, the half-life of bevacizumab in the vitreous and retina was significantly extended, and drug elimination to aqueous humor was effectively reduced. Finally, intraocular stability, degradation, and inflammatory response of hydrogel rods were evaluated. We expect that the hydrogel rod can be a potential drug delivery system for the treatment of nAMD and other conditions that need long-term and local sustained drug administration. STATEMENT OF SIGNIFICANCE: Herein, we report an injectable pre-crosslinked hydrogel rod based on an in situ forming hydrogel to achieve intravitreal long-acting anti-VEGF delivery to reduce injection frequency and improve the long-term visual outcomes of patients with retinal vascular diseases. Hydrogel rods were readily prepared using removable molds and injected using customized injectors. Compared to the in situ forming hydrogel, hydrogel rods showed significantly reduced initial burst release, controllable release profiles for several months, physical stability, and a long-acting anti-angiogenic effect. Animal studies demonstrated that the hydrogel rods dramatically prolonged the intraocular drug half-life while significantly reducing drug elimination for up to four months. Moreover, the biodegradability and safety of the hydrogel rods suggest their suitability as an advanced intravitreal DDS for treating retinal vascular diseases.},
}
@article {pmid37737509,
year = {2023},
author = {Girgis, S and Lee, LR},
title = {Treatment of dry age-related macular degeneration: A review.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {51},
number = {8},
pages = {835-852},
doi = {10.1111/ceo.14294},
pmid = {37737509},
issn = {1442-9071},
mesh = {Humans ; *Geographic Atrophy/therapy ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; },
abstract = {Age-related macular degeneration is a global disease with a significant societal impact. The advent of anti-vascular endothelial growth factor therapy (anti-VEGF) has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). Dry age-related macular degeneration (dAMD) is being investigated for possible therapeutic options. The therapeutic categories undergoing clinical trials include complement pathway inhibitors, visual cycle modulators, reduction of toxic byproducts, antioxidative therapy, neuroprotective agents, laser therapy, surgical options, gene therapy, stem cell therapy, and miscellaneous treatments. Two intravitreal anti-complement factors (pegcetacoplan and avacincaptad pegol) have recently shown phase 3 clinical trial evidence of a reduction in the growth of geographic atrophy. In this review, we provide an update on treatment options currently undergoing clinical research trials for the management of dAMD and preventing the progression of Geographic Atrophy (GA).},
}
@article {pmid37733048,
year = {2023},
author = {Schönbach, EM and Freeman, WR},
title = {Choroidal Detachment After Intravitreal Injection of Faricimab.},
journal = {JAMA ophthalmology},
volume = {141},
number = {9},
pages = {e231067},
doi = {10.1001/jamaophthalmol.2023.1067},
pmid = {37733048},
issn = {2168-6173},
mesh = {Humans ; Intravitreal Injections ; *Choroidal Effusions ; },
}
@article {pmid37732190,
year = {2023},
author = {Grunin, M and Triffon, D and Beykin, G and Rahmani, E and Schweiger, R and Tiosano, L and Khateb, S and Hagbi-Levi, S and Rinsky, B and Munitz, R and Winkler, TW and Heid, IM and Halperin, E and Carmi, S and Chowers, I},
title = {Genome-wide association study and genomic risk prediction of age-related macular degeneration in Israel.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.09.06.23295126},
pmid = {37732190},
abstract = {PURPOSE: The risk of developing age-related macular degeneration(AMD) is influenced by genetic background. In 2016, International AMD Genomics Consortium(IAMDGC) identified 52 risk variants in 34 loci, and a polygenic risk score(PRS) based on these variants was associated with AMD. The Israeli population has a unique genetic composition: Ashkenazi Jewish(AJ), Jewish non-Ashkenazi, and Arab sub-populations. We aimed to perform a genome-wide association study(GWAS) for AMD in Israel, and to evaluate PRSs for AMD.<br><br>METHODS: For our discovery set, we recruited 403 AMD patients and 256 controls at Hadassah Medical Center. We genotyped all individuals via custom exome chip. We imputed non-typed variants using cosmopolitan and AJ reference panels. We recruited additional 155 cases and 69 controls for validation. To evaluate predictive power of PRSs for AMD, we used IAMDGC summary statistics excluding our study and developed PRSs via either clumping/thresholding or LDpred2.<br><br>RESULTS: In our discovery set, 31/34 loci previously reported by the IAMDGC were AMD associated with P<0.05. Of those, all effects were directionally consistent with the IAMDGC and 11 loci had a p-value under Bonferroni-corrected threshold(0.05/34=0.0015). At a threshold of 5x10 [-5] , we discovered four suggestive associations in FAM189A1 , IGDCC4 , C7orf50 , and CNTNAP4 . However, only the FAM189A1 variant was AMD associated in the replication cohort after Bonferroni-correction. A prediction model including LDpred2-based PRS and other covariates had an AUC of 0.82(95%CI:0.79-0.85) and performed better than a covariates-only model(P=5.1x10 [-9]).<br><br>CONCLUSIONS: Previously reported AMD-associated loci were nominally associated with AMD in Israel. A PRS developed based on a large international study is predictive in Israeli populations.},
}
@article {pmid37731202,
year = {2023},
author = {Sun, TB and Huang, KF and Niu, KC and Lin, CH and Liu, WP and Yeh, CH and Kuo, SC and Chang, CP},
title = {Hyperbaric oxygen therapy suppresses hypoxia and reoxygenation injury to retinal pigment epithelial cells through activating peroxisome proliferator activator receptor-alpha signalling.},
journal = {Journal of cellular and molecular medicine},
volume = {27},
number = {20},
pages = {3189-3201},
pmid = {37731202},
issn = {1582-4934},
support = {CMNDMC11101//Chi Mei Medical Center/ ; CMFHR11021//Chi Mei Medical Center/ ; CMFHR11101//Chi Mei Medical Center/ ; CMFHT11103//Chi Mei Medical Center/ ; },
abstract = {Retinal ischemia followed by reperfusion (IR) is a common cause of many ocular disorders, such as age-related macular degeneration (AMD), which leads to blindness in the elderly population, and proper therapies remain unavailable. Retinal pigment epithelial (RPE) cell death is a hallmark of AMD. Hyperbaric oxygen (HBO) therapy can improve IR tissue survival by inducing ischemic preconditioning responses. We conducted an in vitro study to examine the effects of HBO preconditioning on oxygen-glucose deprivation (OGD)-induced IR-injured RPE cells. RPE cells were treated with HBO (100% O2 at 3 atmospheres absolute for 90 min) once a day for three consecutive days before retinal IR onset. Compared with normal cells, the IR-injured RPE cells had lower cell viability, lower peroxisome proliferator activator receptor-alpha (PPAR-α) expression, more severe oxidation status, higher blood-retinal barrier disruption and more elevated apoptosis and autophagy rates. HBO preconditioning increased PPAR-α expression, improved cell viability, decreased oxidative stress, blood-retinal barrier disruption and cellular apoptosis and autophagy. A specific PPAR-α antagonist, GW6471, antagonized all the protective effects of HBO preconditioning in IR-injured RPE cells. Combining these observations, HBO therapy can reverse OGD-induced RPE cell injury by activating PPAR-α signalling.},
}
@article {pmid37731049,
year = {2024},
author = {McGuinness, MB and Robman, L and Hodgson, LAB and Tran, C and Woods, RL and Owen, AJ and McNeil, JJ and Makeyeva, G and Abhayaratna, WP and Guymer, RH},
title = {Diagnostic accuracy of self-reported age-related macular degeneration in the ASPREE Longitudinal Study of Older Persons.},
journal = {Eye (London, England)},
volume = {38},
number = {4},
pages = {698-706},
pmid = {37731049},
issn = {1476-5454},
support = {R01 EY026890/EY/NEI NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; *Australasian People ; Australia/epidemiology ; Longitudinal Studies ; *Macular Degeneration/diagnosis/epidemiology ; Self Report ; },
abstract = {BACKGROUND: The validity of findings from epidemiological studies using self-report of ophthalmic conditions depends on several factors. We assessed the diagnostic accuracy of self-reported age-related macular degeneration (AMD) among older Australians enroled in a primary prevention clinical trial and compared diagnostic accuracy between demographic subgroups.<br><br>METHODS: At baseline (2010-2015), Australian sub-study participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, underwent bilateral two-field, 45&#xb0; non-mydriatic colour retinal photography. Beckman classification of any-stage AMD was used as the reference standard diagnosis. Participants were asked whether a doctor had ever diagnosed them with "macular degeneration" (the index test) via a paper-based questionnaire as part of the ASPREE Longitudinal Study of Older Persons (ALSOP) within the first year of enrolment.<br><br>RESULTS: In total, 4193 participants were included (aged 70-92 years, 50.8% female). Of those, 262 (6.3%) reported having AMD and 92 (2.2%) were unsure. Retinal grading detected 2592 (61.8%) with no AMD, 867 (20.7%) with early, 686 (16.4%) with intermediate and 48 (1.1%) with late AMD (n&#x2009;=&#x2009;1601 with any-stage AMD, 38.2%). Self-reported AMD had 11.4% sensitivity (95% CI 9.9-13.1) and 96.9% specificity (95% CI 96.2-97.6) for any-stage AMD, with 69.8% and 63.9% positive and negative predictive values. Sensitivity was higher among participants with late-stage AMD (87.5%), older participants (26.8%), and those with poorer vision (41.0%).<br><br>CONCLUSIONS: Although most participants with late-stage AMD were aware of having AMD, the majority with early and intermediate AMD were not. Therefore, findings from studies that rely on disease self-report should be interpreted with caution.},
}
@article {pmid37728619,
year = {2023},
author = {Haritoglou, C and Boneva, S and Schultheiss, M and Sebag, J and Binder, S},
title = {[Vitreoretinal surgery in age-related macular degeneration].},
journal = {Die Ophthalmologie},
volume = {120},
number = {10},
pages = {1004-1013},
pmid = {37728619},
issn = {2731-7218},
abstract = {The structure of the vitreous body, its interaction with the retinal surface and tractive alterations of the vitreoretinal interface may play a role in the pathogenesis and the development of age-related macular degeneration (AMD). From clinical trials it can be concluded that posterior vitreous detachment (PVD) or vitreous removal may protect against the development of neovascular AMD. Vitreomacular adhesions may promote neovascular AMD and may have an impact on the efficacy and frequency of intravitreal vascular endothelial growth factor (VEGF) inhibition. Therefore, vitreomacular surgery may be considered as a treatment option in selected cases. Peeling of epimacular membranes and the internal limiting membrane (ILM) may contribute to stabilizing visual acuity and reducing the treatment burden of current intravitreal pharmacotherapy. At present, surgical interventions in AMD are mainly performed in cases of submacular hemorrhage involving the fovea. The treatment is not standardized and consists of liquefaction of the blood using recombinant tissue plasminogen activator (rTPA) and its pneumatic displacement, potentially combined with VEGF inhibition. Other submacular surgical strategies, such as choroidal neovascularization (CNV) extraction, macular translocation or transplantation of retinal pigment epithelium (RPE) are currently limited to selected cases as a salvage treatment; however, the development of these submacular surgical interventions has formed the basis for new approaches in the treatment of dry and neovascular AMD including submacular or intravitreal gene and stem cell therapy.},
}
@article {pmid37728589,
year = {2024},
author = {Zhao, N and Hao, XN and Huang, JM and Song, ZM and Tao, Y},
title = {Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation.},
journal = {Aging and disease},
volume = {15},
number = {3},
pages = {1132-1154},
pmid = {37728589},
issn = {2152-5250},
mesh = {Humans ; *Macular Degeneration/pathology/therapy/immunology ; *Ependymoglial Cells/pathology ; *Microglia/pathology/immunology ; Neuroinflammatory Diseases/pathology/immunology ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is a progressive neurodegeneration disease that causes photoreceptor demise and vision impairments. In AMD pathogenesis, the primary death of retinal neurons always leads to the activation of resident microglia. The migration of activated microglia to the ongoing retinal lesion and their morphological transformation from branching to ameboid-like are recognized as hallmarks of AMD pathogenesis. Activated microglia send signals to Müller cells and promote them to react correspondingly to damaging stimulus. Müller cells are a type of neuroglia cells that maintain the normal function of retinal neurons, modulating innate inflammatory responses, and stabilize retinal structure. Activated Müller cells can accelerate the progression of AMD by damaging neurons and blood vessels. Therefore, the crosstalk between microglia and Müller cells plays a homeostatic role in maintaining the retinal environment, and this interaction is complicatedly modulated. In particular, the mechanism of mutual regulation between the two glia populations is complex under pathological conditions. This paper reviews recent findings on the crosstalk between microglia and Müller glia during AMD pathology process, with special emphasis on its therapeutic potentials.},
}
@article {pmid37728563,
year = {2023},
author = {Farjood, F and Manos, JD and Wang, Y and Williams, AL and Zhao, C and Borden, S and Alam, N and Prusky, G and Temple, S and Stern, JH and Boles, NC},
title = {Identifying biomarkers of heterogeneity and transplantation efficacy in retinal pigment epithelial cells.},
journal = {The Journal of experimental medicine},
volume = {220},
number = {12},
pages = {},
pmid = {37728563},
issn = {1540-9538},
support = {R01 EY032138/EY/NEI NIH HHS/United States ; U01 EY030581/EY/NEI NIH HHS/United States ; R01 EY022079/EY/NEI NIH HHS/United States ; R01EY032138/NH/NIH HHS/United States ; R01 EY029281/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Rats ; Biomarkers ; *Gene Expression Profiling ; *Neurons ; Epithelial Cells ; Retinal Pigments ; },
abstract = {Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats. scRNA-seq revealed several distinct subpopulations in the RPESC-RPE product, some with progenitor markers. We identified RPE clusters expressing genes associated with in vivo efficacy and increased cell integration capability. Gene expression analysis revealed lncRNA (TREX) as a predictive marker of in vivo efficacy. TREX knockdown decreased cell integration while overexpression increased integration in vitro and improved vision rescue in the RCS rats.},
}
@article {pmid37727019,
year = {2024},
author = {Lin, W and Li, D and Wen, L and Wang, Y and Lin, Z and Wang, F and Liang, Y},
title = {Prevalence and Risk Factors of Fundus Pathology in Patients with Type 2 Diabetes in a Northeastern Chinese Cohort.},
journal = {Ophthalmic epidemiology},
volume = {31},
number = {4},
pages = {356-363},
doi = {10.1080/09286586.2023.2260855},
pmid = {37727019},
issn = {1744-5086},
mesh = {Humans ; *Diabetes Mellitus, Type 2/epidemiology/complications ; Male ; Female ; Middle Aged ; Prevalence ; Risk Factors ; China/epidemiology ; Aged ; *Diabetic Retinopathy/epidemiology/diagnosis ; Fundus Oculi ; Adult ; Macular Degeneration/epidemiology/diagnosis ; Cohort Studies ; East Asian People ; },
abstract = {PURPOSE: To assess the prevalence of and risk factors for fundus pathology in patients with type 2 diabetes mellitus (T2DM) in a cohort from northeastern China.<br><br>METHODS: Patients were included from the Fushun Diabetic Retinopathy Cohort Study. Patients aged&#x2009;&#x2265;&#x2009;30&#x2009;years with T2DM were recruited between July 2012 and May 2013. Fundus pathology included retinal vascular occlusion (RVO), age-related macular degeneration (AMD), macular pathology, pathologic myopia (PM) and glaucomatous optic atrophy (GOA).<br><br>RESULTS: A Total of 1998 patients with gradable fundus photographs were included in this study, of whom 388 (19.42%) had fundus pathology regardless of whether they had diabetic retinopathy (DR). There were 187 (9.36%) patients with AMD, 97 (4.85%) with GOA, 67 (3.35%) with macular pathology, 35 (1.75%) with PM and 23 (1.15%) with RVO. Advanced age was significantly associated with AMD (odds ratio (OR), 95% confidence interval (CI): 1.03, 1.01-1.05), macular pathology (OR, 95% CI: 1.06, 1.03-1.09) and GOA (OR, 95% CI: 1.06, 1.04-1.09). A wider central retinal arteriolar equivalent was protective against PM (OR, 95% CI: 0.78, 0.66-0.92). Wider central retinal venular equivalent was a protective factor for PM (OR, 95% CI: 0.75, 0.68-0.82) and GOA (OR, 95% CI: 0.93, 0.87-0.99).<br><br>CONCLUSIONS: One-fifth of these patients in northeast China with T2DM had fundus pathology regardless of whether they had DR, indicating the importance of early screening and long-term follow-up.},
}
@article {pmid37726145,
year = {2024},
author = {Matchinski, TL and Crumbliss, KE and Corgiat, E and Pang, Y},
title = {Near prescribing trends in two low vision rehabilitation clinics over a ten-year period.},
journal = {Clinical &amp; experimental optometry},
volume = {107},
number = {5},
pages = {563-570},
doi = {10.1080/08164622.2023.2246490},
pmid = {37726145},
issn = {1444-0938},
mesh = {Humans ; Retrospective Studies ; *Vision, Low/rehabilitation ; Female ; Male ; Middle Aged ; Adult ; *Prescriptions/statistics &amp; numerical data ; Aged ; Adolescent ; *Visual Acuity ; Young Adult ; Child ; Child, Preschool ; Eyeglasses ; Infant ; Aged, 80 and over ; Practice Patterns, Physicians'/statistics &amp; numerical data/trends ; Infant, Newborn ; },
abstract = {CLINICAL RELEVANCE: Optical magnification (OM), electronic magnification (EM), and assistive technology (AT) can be prescribed in low vision rehabilitation (LVR) clinics for near vision goals of patients. This study shows the prescription of OM has not decreased with increased availability of EM and AT.<br><br>BACKGROUND: Near visual goals are a primary concern for patients with visual impairment. LVR providers can prescribe OM, EM and/or AT to help. With the rapid evolution and availability of EM and AT, we aim to evaluate if there have been changes in the prescription patterns of clinicians with respect to OM over time. We hypothesise that the increased availability of technology may result in declining prescriptions of OM and increasing prescription of EM and AT over time.<br><br>METHODS: This retrospective study investigated near prescribing between 2008-2017 for 530 new patients to the LVR clinics. Examinations were performed by optometrists specialising in low vision. Near devices prescribed included OM and EM and AT.<br><br>RESULTS: Most patients attending the LVR clinics were female, over 60&#x2009;years old and had age related macular degeneration. Near visual goals were a primary concern of 97.2% of the patients. OM was most prescribed in the 0-19 and&#x2009;>60-year-old age groups. Within the 20-39-year-old age group there was the greatest number of both EM and AT prescriptions. OM was most prescribed in patients with visual acuity better than 6/60. EM and AT showed a trend of increasing prescription as visual acuity decreased. EM prescription peaked in&#x2009;<6/60 to 6/240 category while AT trended upwards from&#x2009;<6/21 to no light perception and peaked in patients with no light perception. Referral rates for additional rehabilitation services were 75.7%.<br><br>CONCLUSIONS: This study shows that the prescription of OM is not declining even as the prescription and the breadth of electronic magnification and assistive technology available is expanding. OM continues to be a viable option for patients, especially in the youngest and oldest cohorts.},
}
@article {pmid37725382,
year = {2023},
author = {Mao, D and Tao, B and Sheng, S and Jin, H and Chen, W and Gao, H and Deng, J and Li, Z and Chen, F and Chan, S and Qian, L},
title = {Causal Effects of Gut Microbiota on Age-Related Macular Degeneration: A Mendelian Randomization Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {12},
pages = {32},
pmid = {37725382},
issn = {1552-5783},
mesh = {Eubacterium ; Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; Clostridiales ; Genome-Wide Association Study ; Humans ; *Macular Degeneration/genetics ; },
abstract = {PURPOSE: Recently, the association between gut microbiota and age-related macular degeneration (AMD) through the gut-retina axis has attracted great interest. However, the causal relationship between them has not been elucidated. Using publicly available genome-wide association study summary statistics, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiota and the occurrence of AMD.<br><br>METHODS: The study used a variety of quality control techniques to select instrumental single nucleotide polymorphisms (SNPs) with strong exposure associations. We used a set of SNPs as instrumental variable that were below the genome-wide statistical significance threshold (5 &#xd7; 10-8). Additionally, a separate group of SNPs below the locus-wide significance level (1 &#xd7; 10-5) were selected as instrumental variables to ensure a comprehensive conclusion. Inverse variance-weighted (IVW) analysis was the primary technique we used to examine causality in order to confirm the validity of our findings. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate the horizontal pleiotropy, heterogeneities, and stability of the genetic variants.<br><br>RESULTS: IVW results showed that genus Anaerotruncus (P&#xa0;=&#xa0;5.00 &#xd7; 10-3), genus Candidatus Soleaferrea (P&#xa0;=&#xa0;1.83 &#xd7; 10-2), and genus unknown id.2071 (P&#xa0;=&#xa0;3.12 &#xd7; 10-2) were protective factors for AMD. The Eubacterium oxidoreducens group (P&#xa0;=&#xa0;3.17 &#xd7; 10-2), genus Faecalibacterium (P&#xa0;=&#xa0;2.67 &#xd7; 10-2), and genus Ruminococcaceae UCG-011 (P&#xa0;=&#xa0;4.04 &#xd7; 10-2) were risk factors of AMD. No gut microbiota (GM) taxa were found to be causally related to AMD at the phylum, class, order, and family levels (P&#xa0;>&#xa0;0.05). The robustness of MR results were confirmed by heterogeneity and pleiotropy analysis. (P&#xa0;>&#xa0;0.05). We also performed a bidirectional analysis, which showed that genus Anaerotruncus, genus Candidatus Soleaferrea, genus unknown id.2071 and the Eubacterium oxidoreducens group had an interaction with AMD, whereas genus Faecalibacterium showed only a unilateral unfavorable effect on AMD.<br><br>CONCLUSIONS: We confirmed a causal relationship between AMD and GM taxa, including the Eubacterium oxidoreducens group, Faecalibacterium, Ruminococcaceae UCG-011, Anaerotruncus, and Candidatus Soleaferrea. These strains have the potential to serve as new biomarkers, offering valuable insights into the treatment and prevention of AMD.},
}
@article {pmid37724918,
year = {2024},
author = {Bagi Nordsten, C and Rasmussen, BK and Li, X and Thomsen, AK and Sørensen, TL},
title = {Impact of COVID-19 restrictions on the treatment of neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {3},
pages = {e404-e405},
doi = {10.1111/aos.15766},
pmid = {37724918},
issn = {1755-3768},
mesh = {Humans ; *COVID-19 ; Ranibizumab ; Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; Tomography, Optical Coherence ; },
}
@article {pmid37724273,
year = {2023},
author = {Datseris, I and Bouratzis, N and Kotronis, C and Datseris, I and Tzanidaki, ME and Rouvas, A and Gouliopoulos, N},
title = {One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {16},
number = {9},
pages = {1496-1502},
pmid = {37724273},
issn = {2222-3959},
abstract = {AIM: To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration (AMD).<br><br>METHODS: Fifty na&#xef;ve and previously untreated patients suffering from wet AMD, were randomly assigned in two subgroups of 25 patients each. All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept (IAIs) followed by injections "according to need", while in one group the patients also received daily two tablets of resveratrol oral supplement. Prior to treatment initiation, a complete ophthalmological examination, including best corrected visual acuity (BCVA) and contrast sensitivity evaluation, optical coherence tomography (OCT) scans, fundus autofluorescence (FAF), fluorescein angiography, indocyanine green angiography, and OCT angiography (OCTA), was performed to every participant, while all of them completed the Hospital Anxiety and Depression Scale (HADS) questionnaire, in order to assess their quality of life (QoL) status. The patients were assessed monthly for 1y with FAF, and OCT or OCTA; the main endpoints were the number IAIs, the changes in BCVA, in contrast sensitivity, and in patients' QoL status.<br><br>RESULTS: No significant differences were present between the groups regarding the baseline demographic and clinical data. Over the 12-month period, a similar number of IAIs was applied in both groups (4.52&#xb1;1.00 vs 4.28&#xb1;0.90, P=0.38), while the rest of the clinical data also did not differ significantly after the completion of the study period. However, for HADS Depression (11.88&#xb1;2.51 vs 8.28&#xb1;1.54, P<0.001) and HADS Anxiety (11.92&#xb1;2.52 vs 7.76&#xb1;1.51, P<0.001) questionnaires values, the score was significantly better in patients who received resveratrol supplements. Moreover, a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity (0.17&#xb1;0.19 vs 0.35&#xb1;0.24, P=0.005), HADS Depression (0.08&#xb1;1.38 vs -3.88&#xb1;1.48, P<0.001), and HADS Anxiety (0.36&#xb1;1.98 vs -5.12&#xb1;2.70, P<0.001) scores, in favour of the patients treated with resveratrol supplements.<br><br>CONCLUSION: The resveratrol oral supplement is a complementary treatment in cases of wet AMD, highlighting its effectiveness in improving patients' QoL status.},
}
@article {pmid37724264,
year = {2023},
author = {Chen, XD and Li, C and Ding, GL and Suo, Y and Zhu, YS and Lu, HQ},
title = {Clinical efficacy and changes of serum VEGF-A, VEGF-B, and PLGF after conbercept treating neovascular age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {16},
number = {9},
pages = {1489-1495},
pmid = {37724264},
issn = {2222-3959},
abstract = {AIM: To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PLGF) levels after intravitreal injections for the neovascular age-related macular degeneration (AMD).<br><br>METHODS: Thirty-five patients (35 eyes) with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were detected before the intravitreal injection and at 1, 3, and 12mo after conbercept treatment. The levels of serum VEGF-A, VEGF-B, and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments.<br><br>RESULTS: At baseline, the mean BCVA score was 39.89&#xb1;14.64 letters. The mean BCVA scores were 51.03&#xb1;15.78, 56.71&#xb1;14.38, and 52.49&#xb1;10.16 letters at 1, 3, and 12mo after conbercept treatment, and the BCVA improvements were all significant, respectively (P<0.05). At baseline, the mean CRT was 436.7&#xb1;141.9 &#xb5;m. At 1, 3, and 12mo after conbercept treatment, the mean CRT values were 335.1&#xb1;147.8, 301.1&#xb1;116.5, and 312.2&#xb1;98.22 &#xb5;m, and the CRT improvements were all significant, respectively (P<0.05). At baseline, 1 and 12mo after conbercept treatment, the mean levels of serum VEGF-A were 1013.8&#xb1;454.3, 953.1&#xb1;426.4, and 981.5&#xb1;471.7 pg/mL, the mean levels of serum VEGF-B were 46.93&#xb1;24.76, 42.99&#xb1;19.16, and 45.32&#xb1;18.76 pg/mL, the mean levels of serum PLGF at these points were 251.7&#xb1;154.9, 241.3&#xb1;166.7, and 245.6&#xb1;147.2 pg/mL, respectively. Compared with the baseline, the levels of serum VEGF-A, VEGF-B, and PLGF did not significantly change at 1 and 12mo after conbercept treatment, respectively (P>0.05).<br><br>CONCLUSION: Conbercept intravitreal injection leads to BCVA and CRT improvement, however, it does not significantly affect systemic serum VEGF-A, VEGF-B, and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.},
}
@article {pmid37722240,
year = {2023},
author = {Bigini, F and Lee, SH and Sun, YJ and Sun, Y and Mahajan, VB},
title = {Unleashing the potential of CRISPR multiplexing: Harnessing Cas12 and Cas13 for precise gene modulation in eye diseases.},
journal = {Vision research},
volume = {213},
number = {},
pages = {108317},
pmid = {37722240},
issn = {1878-5646},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; R01 EY031952/EY/NEI NIH HHS/United States ; R01 EY025295/EY/NEI NIH HHS/United States ; I01 CX001481/CX/CSRD VA/United States ; K08 EY022058/EY/NEI NIH HHS/United States ; R01 EY030151/EY/NEI NIH HHS/United States ; R01 EY031360/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *CRISPR-Cas Systems/genetics ; Gene Editing ; RNA, Messenger ; Eye ; *Eye Diseases/genetics/therapy ; },
abstract = {Gene therapy is a flourishing field with the potential to revolutionize the treatment of genetic diseases. The emergence of CRISPR-Cas9 has significantly advanced targeted and efficient genome editing. Although CRISPR-Cas9 has demonstrated promising potential applications in various genetic disorders, it faces limitations in simultaneously targeting multiple genes. Novel CRISPR systems, such as Cas12 and Cas13, have been developed to overcome these challenges, enabling multiplexing and providing unique advantages. Cas13, in particular, targets mRNA instead of genomic DNA, permitting precise gene expression control and mitigating off-target effects. This review investigates the potential of Cas12 and Cas13 in ocular gene therapy applications, such as suppression of inflammation and cell death. In addition, the capabilities of Cas12 and Cas13 are explored in addressing potential targets related with disease mechanisms such as aberrant isoforms, mitochondrial genes, cis-regulatory sequences, modifier genes, and long non-coding RNAs. Anatomical accessibility and relative immune privilege of the eye provide an ideal organ system for evaluating these novel techniques' efficacy and safety. By targeting multiple genes concurrently, CRISPR-Cas12 and Cas13 systems hold promise for treating a range of ocular disorders, including glaucoma, retinal dystrophies, and age-related macular degeneration. Nonetheless, additional refinement is required to ascertain the safety and efficacy of these approaches in ocular disease treatments. Thus, the development of Cas12 and Cas13 systems marks a significant advancement in gene therapy, offering the potential to devise effective treatments for ocular disorders.},
}
@article {pmid37721739,
year = {2023},
author = {Herold, JM and Zimmermann, ME and Gorski, M and Günther, F and Weber, BHF and Helbig, H and Stark, KJ and Heid, IM and Brandl, C},
title = {Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {12},
pages = {31},
pmid = {37721739},
issn = {1552-5783},
mesh = {Humans ; Cross-Sectional Studies ; *Macular Degeneration/diagnosis/genetics ; Area Under Curve ; Fundus Oculi ; Risk Factors ; },
abstract = {PURPOSE: The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD.<br><br>METHODS: In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universit&#xe4;t Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage.<br><br>RESULTS: We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC "age-related changes" and CC "early AMD" distinguished individuals with 3CACSS "no AMD"; 3CACSS "mild/moderate/severe early AMD" stages, and distinguished CC "intermediate AMD". This suggested a 7-step scale combining the 2 systems: (i) "no AMD", (ii) "age-related changes", (iii) "very early AMD", (i.e. CC "early"), (iv) "mild early AMD", (v) "moderate early AMD", (vi) "severe early AMD", and (vii) "late AMD". GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC "no AMD without age-related changes": AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI&#xa0;=&#xa0;59.1, 65.6, AUC = 63.8%, 95% CI&#xa0;=&#xa0;59.3, 68.3, AUC&#xa0;=&#xa0;78.1%, 95% CI&#xa0;=&#xa0;73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area.<br><br>CONCLUSIONS: The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group.},
}
@article {pmid37721532,
year = {2023},
author = {Dähmcke, M and Busch, M and Pfeil, JM and Brauckmann, T and Schulz, D and Omran, W and Morawiec-Kisiel, E and Wähler, F and Paul, S and Tayar, A and Bründer, MC and Grundel, B and Stahl, A},
title = {Circulating MicroRNAs as Biomarker for Vessel-Associated Retinal Diseases.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {3-4},
pages = {227-237},
doi = {10.1159/000533481},
pmid = {37721532},
issn = {1423-0267},
mesh = {Humans ; *Circulating MicroRNA/genetics ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; *MicroRNAs/genetics ; *Diabetic Retinopathy ; Biomarkers ; },
abstract = {INTRODUCTION: Vessel-associated retinal diseases are a major cause of blindness and severe visual impairment. The identification of appropriate biomarkers is of great importance to better anticipate disease progression and establish more targeted treatment options. MicroRNAs (miRNAs) are short, single-stranded, noncoding ribonucleic acids that are involved in the posttranscriptional regulation of gene expression through hybridization with messenger RNA. The expression of certain miRNAs can be different in patients with pathological processes and can be used for the detection and differentiation of various diseases. In this study, we investigate to what extent previously in vitro identified miRNAs are present as cell-free circulating miRNAs in the serum and vitreous of human patients with and without vessel-associated retinal diseases.<br><br>METHODS: Relative quantification by quantitative real-time polymerase chain reaction was used to analyze miRNA expression in patients with vessel-associated retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion compared with control patients.<br><br>RESULTS: In serum samples, miR-29a-3p and miR-192-5p showed increased expression in patients with neovascular AMD relative to control patients. Similarly, miR-335-5p, miR-192-5p, and miR-194-5p showed increased expression in serum from patients with proliferative DR. In vitreous samples, miR-100-5p was decreased in patients with proliferative DR. Differentially expressed miRNAs showed good diagnostic accuracy in receiver operating characteristic (ROC) and area under the ROC curve analysis.<br><br>CONCLUSION: The miRNAs investigated in this study may have the potential to serve as biomarkers for vessel-associated retinal diseases. Combining multiple miRNAs may enhance the predictive power of the analysis.},
}
@article {pmid37720026,
year = {2023},
author = {Dieckmann, BW and Paguaga, ME and McCollum, GW and Penn, JS and Uddin, I},
title = {Role of NLRP3 inflammasomes in monocyte and microglial recruitments in choroidal neovascularization.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {37720026},
issn = {2693-5015},
support = {P30 EY008126/EY/NEI NIH HHS/United States ; R01 EY023397/EY/NEI NIH HHS/United States ; R01 EY029693/EY/NEI NIH HHS/United States ; },
abstract = {Though the pathogenesis of choroidal neovascularization (CNV) is largely unknown in age-related macular degeneration (AMD), inflammasomes may contribute to CNV development and progression. To understand the role NLRP3 inflammasomes in CNV, we used Ccr2[RFP]Cx3cr1[GFP] dual-reporter mice to characterize migration of Ccr2[RFP] positive monocytes and Cx3cr1[GFP] positive microglial cells into CNV lesions after laser-induced rupture of Bruch's membrane. MCC950 was used as NLRP3 inhibitor. Immunostaining was used to confirm localization of NLRP3 inflammasomes in the LCNV lesions. Confocal microscopy was used to image and quantify LCNV volumes. ELISA and qRT-PCR were used to confirm the activation of NLRP3 by monitoring the expression of IL-1β protein and mRNA in choroidal tissues from LCNV mice. In addition, NLRP3 (-/-) LCNV mice were used to investigate whether NLRP3 inflammasomes contribute to the development of LCNV lesions. We observed that RFP positive monocyte-derived macrophages and GFP positive microglia-derived macrophages, in addition to other cell types, were localized in LCNV lesions at day 7 post-laser injury. In addition, NLRP3 inflammasomes are associated with LCNV lesions. Inhibition of NLRP3 inflammasomes, using MCC950, caused an increased Ccr2[RFP] positive macrophages, Cx3cr1[GFP] positive microglia, and other cells resulting in an increase in total lesion size. NLRP3 (-/-) LCNV mice, showed significantly increased lesion size compared to age-matched controls. Inhibition of NLRP3, resulted in decreased IL-1β mRNA and protein expression in the choroidal tissues, suggesting that increased lesion size may not be directly related to IL-1β.},
}
@article {pmid37717737,
year = {2024},
author = {Agrón, E and Domalpally, A and Cukras, CA and Chew, EY and Keenan, TDL and , },
title = {Critical Dependence on Area in Relationship between ARMS2/HTRA1 Genotype and Faster Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report Number 33.},
journal = {Ophthalmology},
volume = {131},
number = {2},
pages = {208-218},
pmid = {37717737},
issn = {1549-4713},
support = {Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Alleles ; Atrophy ; Disease Progression ; Eye ; Genotype ; *Geographic Atrophy/diagnosis/genetics ; *Macular Degeneration/genetics ; Proteins/genetics ; },
abstract = {PURPOSE: To analyze ARMS2/HTRA1 as a risk factor for faster geographic atrophy (GA) enlargement according to (1) GA area and (2) contiguous enlargement versus progression to multifocality.<br><br>DESIGN: Age-Related Eye Disease Study 2 (AREDS2) cohort analysis.<br><br>PARTICIPANTS: Eyes with GA: 546 eyes of 406 participants.<br><br>METHODS: Geographic atrophy area was measured from color fundus photographs at annual visits. Mixed-model regression of square root of GA area and proportional hazards regression of progression to multifocality were analyzed by ARMS2 genotype.<br><br>MAIN OUTCOME MEASURES: Change in square root GA area and progression to multifocality.<br><br>RESULTS: Geographic atrophy enlargement was significantly faster with ARMS2 risk alleles (P < 0.0001) at 0.224 mm/year (95% CI, 0.195-0.252 mm/year), 0.298 mm/year (95% CI, 0.271-0.324 mm/year), and 0.317 mm/year (95% CI, 0.279-0.355 mm/year), for 0 to 2 risk alleles, respectively. However, a significant interaction (P&#xa0;= 0.011) was observed between genotype and baseline area. In eyes with very small area (< 1.9 mm[2]), enlargement was significantly faster with ARMS2 risk alleles (P < 0.0001) at 0.193 mm/year (95% CI, 0.162-0.225 mm/year) versus 0.304 mm/year (95% CI, 0.280-0.329 mm/year) for 0 versus 1 to 2 risk alleles, respectively. With moderately small (1.9-3.8 mm[2]) or medium to large (&#x2265; 3.8 mm[2]) area, enlargement was not significantly faster with ARMS2 risk alleles (P&#xa0;= 0.66 and P&#xa0;= 0.70, respectively). In nonmultifocal GA, enlargement was significantly faster with ARMS2 risk alleles (P&#xa0;= 0.001) at 0.175 mm/year (95% CI, 0.142-0.209 mm/year), 0.226 mm/year (95% CI, 0.193-0.259 mm/year), and 0.287 mm/year (95% CI, 0.237-0.337 mm/year) with 0 to 2 risk alleles, respectively. ARMS2 genotype was not associated significantly with progression to multifocal GA.<br><br>CONCLUSIONS: The relationship between ARMS2/HTRA1 genotype and faster GA enlargement depends critically on GA area: risk alleles represent a strong risk factor for faster enlargement only in eyes with very small area. They increase the growth rate more through contiguous enlargement than progression to multifocality. ARMS2/HTRA1 genotype is more important in increasing risk of progression to GA and initial GA enlargement (contiguously) than in subsequent enlargement or progression to multifocality. These findings may explain some discrepancies between previous studies and have implications for both research and clinical practice.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37716480,
year = {2024},
author = {Choi, A and Nawash, BS and Du, K and Ong, J and Chhablani, J},
title = {Barriers to care in neovascular age-related macular degeneration: Current understanding, developments, and future directions.},
journal = {Survey of ophthalmology},
volume = {69},
number = {1},
pages = {160-164},
doi = {10.1016/j.survophthal.2023.09.001},
pmid = {37716480},
issn = {1879-3304},
mesh = {Humans ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Health Services Accessibility ; *Wet Macular Degeneration/drug therapy ; Ranibizumab/therapeutic use ; Treatment Outcome ; },
abstract = {Neovascular age-related macular degeneration is the advanced and irreversible stage of age-related macular degeneration, the leading cause of severe vision loss in older adults. While anti-vascular endothelial growth factor injections have been shown to preserve or improve vision quality in eyes with neovascular age-related macular degeneration, the treatment regimen can be demanding of patients and caregivers, leading to lower rates of adherence. Therefore, it is crucial that disparities and obstacles in neovascular age-related macular degeneration care are identified to improve access to treatment. Review of the current literature revealed 7 major categories of barriers: travel burden, psychological barriers, financial burden and socioeconomic status, treatment regimen, other comorbidities, provider-level barriers, and system-level barriers. We provide an overview of the major barriers to neovascular age-related macular degeneration care that have been reported, as well as gaps in research that need to be investigated further.},
}
@article {pmid37715632,
year = {2024},
author = {Barayev, E and Tiosano, A and Zlatkin, R and Elul, R and Dotan, A and Hadayer, A and Gal-Or, O and Ehrlich, R},
title = {Prognostic factors for visual acuity improvement after treatment of submacular hemorrhage secondary to exudative age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {34},
number = {3},
pages = {825-833},
doi = {10.1177/11206721231202048},
pmid = {37715632},
issn = {1724-6016},
mesh = {Humans ; *Visual Acuity/physiology ; Retrospective Studies ; Male ; Female ; *Tomography, Optical Coherence ; *Retinal Hemorrhage/etiology/diagnosis/therapy/physiopathology ; Aged, 80 and over ; *Wet Macular Degeneration/diagnosis/complications/physiopathology/drug therapy ; *Vitrectomy ; *Tissue Plasminogen Activator/administration &amp; dosage/therapeutic use ; Prognosis ; *Intravitreal Injections ; Fibrinolytic Agents/therapeutic use/administration &amp; dosage ; Fluorescein Angiography ; Aged ; Endotamponade ; Follow-Up Studies ; },
abstract = {PURPOSE: To recognize prognostic factors for better final visual acuity (VA) in patients presenting with submacular hemorrhage (SMH) secondary to exudative age-related macular degeneration.<br><br>METHODS: This retrospective study included patients who presented to a tertiary ophthalmology department between 2012 and 2019 with SMH and were treated by pars plana vitrectomy (PPV) or injection of tissue plasminogen activator (tPA) with pneumatic displacement. Baseline characteristics included demographic data, VA and optical coherence tomography (OCT) characteristics of the SMH. Patients were divided into groups by improvement of at least 2 lines in BCVA (best corrected visual acuity), and by having a final BCVA better than 20/200.<br><br>RESULTS: Forty-three eyes of 43 patients were included. Mean age was 86.72&#x2009;&#xb1;&#x2009;7.18. Prognostic factors for final VA better than 20/200 included better VA at presentation (1.25 vs 1.90 logMAR, p&#x2009;<&#x2009;0.001), smaller area of SMH in the infra-red image (19.47 mm[2] vs 38.45 mm[2], p&#x2009;=&#x2009;0.024), and lower height of SMH as measured by OCT (713.5&#x2005;&#xb5;m vs 962.5&#x2005;&#xb5;m, p&#x2009;=&#x2009;0.03). Third of the patients improved in &#x2265;2 lines from presentation, all in the group of the pneumatic and TPA displacement.<br><br>CONCLUSION: Smaller SMHs with good VA at presentation have a better chance for improvement and result in a better final VA. These patients may benefit the most from pneumatic displacement of the SMH with intravitreal tPA and gas.},
}
@article {pmid37713276,
year = {2023},
author = {Kramer, RH},
title = {Suppressing Retinal Remodeling to Mitigate Vision Loss in Photoreceptor Degenerative Disorders.},
journal = {Annual review of vision science},
volume = {9},
number = {},
pages = {131-153},
doi = {10.1146/annurev-vision-112122-020957},
pmid = {37713276},
issn = {2374-4650},
mesh = {Humans ; *Vision Disorders ; Retina ; Retinal Cone Photoreceptor Cells ; *Retinal Neurons ; Tretinoin ; },
abstract = {Rod and cone photoreceptors degenerate in retinitis pigmentosa and age-related macular degeneration, robbing the visual system of light-triggered signals necessary for sight. However, changes in the retina do not stop with the photoreceptors. A stereotypical set of morphological and physiological changes, known as remodeling, occur in downstream retinal neurons. Some aspects of remodeling are homeostatic, with structural or functional changes compensating for partial loss of visual inputs. However, other aspects are nonhomeostatic, corrupting retinal information processing to obscure vision mediated naturally by surviving photoreceptors or artificially by vision-restoration technologies. In this review, I consider the mechanism of remodeling and its consequences for residual and restored visual function; discuss the role of retinoic acid, a critical molecular trigger of detrimental remodeling; and discuss strategies for suppressing retinoic acid biosynthesis or signaling as therapeutic possibilities for mitigating vision loss.},
}
@article {pmid37713257,
year = {2023},
author = {Plau, J and Morgan, CE and Fedorov, Y and Banerjee, S and Adams, DJ and Blaner, WS and Yu, EW and Golczak, M},
title = {Discovery of Nonretinoid Inhibitors of CRBP1: Structural and Dynamic Insights for Ligand-Binding Mechanisms.},
journal = {ACS chemical biology},
volume = {18},
number = {10},
pages = {2309-2323},
pmid = {37713257},
issn = {1554-8937},
support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 AI145069/AI/NIAID NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; S10 OD021527/OD/NIH HHS/United States ; R01 EY023948/EY/NEI NIH HHS/United States ; R01 DK122071/DK/NIDDK NIH HHS/United States ; P30 GM124165/GM/NIGMS NIH HHS/United States ; R01 DK068437/DK/NIDDK NIH HHS/United States ; },
mesh = {Animals ; Mice ; Retinol-Binding Proteins, Cellular/metabolism ; Ligands ; *Vitamin A/metabolism ; *Eye ; Carrier Proteins ; },
abstract = {The dysregulation of retinoid metabolism has been linked to prevalent ocular diseases including age-related macular degeneration and Stargardt disease. Modulating retinoid metabolism through pharmacological approaches holds promise for the treatment of these eye diseases. Cellular retinol-binding protein 1 (CRBP1) is the primary transporter of all-trans-retinol (atROL) in the eye, and its inhibition has recently been shown to protect mouse retinas from light-induced retinal damage. In this report, we employed high-throughput screening to identify new chemical scaffolds for competitive, nonretinoid inhibitors of CRBP1. To understand the mechanisms of interaction between CRBP1 and these inhibitors, we solved high-resolution X-ray crystal structures of the protein in complex with six selected compounds. By combining protein crystallography with hydrogen/deuterium exchange mass spectrometry, we quantified the conformational changes in CRBP1 caused by different inhibitors and correlated their magnitude with apparent binding affinities. Furthermore, using molecular dynamic simulations, we provided evidence for the functional significance of the "closed" conformation of CRBP1 in retaining ligands within the binding pocket. Collectively, our study outlines the molecular foundations for understanding the mechanism of high-affinity interactions between small molecules and CRBPs, offering a framework for the rational design of improved inhibitors for this class of lipid-binding proteins.},
}
@article {pmid37709925,
year = {2024},
author = {Bullimore, MA and Brennan, NA},
title = {Juvenile-onset myopia-who to treat and how to evaluate success.},
journal = {Eye (London, England)},
volume = {38},
number = {3},
pages = {450-454},
pmid = {37709925},
issn = {1476-5454},
mesh = {Child ; Humans ; Refraction, Ocular ; Mydriatics/therapeutic use ; Treatment Outcome ; *Myopia, Degenerative ; *Macular Degeneration ; Disease Progression ; },
abstract = {The risk of eye diseases such as myopic macular degeneration increases with the level of myopia, but there is no safe level of myopia and the burden of lower degrees of myopia remains considerable. Effective treatments are available that slow progression and thus limit the final degree of myopia. In this review, the rationale for slowing progression is summarized, and a case made for treating all myopic children. Measurement of refractive error and axial length is reviewed, stressing the precision of optical biometry, but also the need for cycloplegic autorefraction. The factors influencing progression are considered and the available tools for interpretation of progression rate are discussed. Finally, the need to set attainable treatment goals is emphasized.},
}
@article {pmid37709773,
year = {2023},
author = {Chen, X and Shi, C and He, M and Xiong, S and Xia, X},
title = {Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.},
journal = {Signal transduction and targeted therapy},
volume = {8},
number = {1},
pages = {352},
pmid = {37709773},
issn = {2059-3635},
mesh = {Humans ; *Endoplasmic Reticulum Stress/genetics ; Unfolded Protein Response/genetics ; *Color Vision Defects ; Autophagy/genetics ; Epigenomics ; },
abstract = {The endoplasmic reticulum (ER) functions as a quality-control organelle for protein homeostasis, or "proteostasis". The protein quality control systems involve ER-associated degradation, protein chaperons, and autophagy. ER stress is activated when proteostasis is broken with an accumulation of misfolded and unfolded proteins in the ER. ER stress activates an adaptive unfolded protein response to restore proteostasis by initiating protein kinase R-like ER kinase, activating transcription factor 6, and inositol requiring enzyme 1. ER stress is multifaceted, and acts on aspects at the epigenetic level, including transcription and protein processing. Accumulated data indicates its key role in protein homeostasis and other diverse functions involved in various ocular diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, achromatopsia, cataracts, ocular tumors, ocular surface diseases, and myopia. This review summarizes the molecular mechanisms underlying the aforementioned ocular diseases from an ER stress perspective. Drugs (chemicals, neurotrophic factors, and nanoparticles), gene therapy, and stem cell therapy are used to treat ocular diseases by alleviating ER stress. We delineate the advancement of therapy targeting ER stress to provide new treatment strategies for ocular diseases.},
}
@article {pmid37709171,
year = {2024},
author = {Johnson-Griggs, MA and Hicks, PM and Lu, MC and Sherman, E and Niziol, LM and Elam, AR and Woodward, MA and Bicket, AK and Killeen, OJ and Wood, S and John, D and Johnson, L and Kershaw, M and Musch, DC and Newman-Casey, PA},
title = {Relationship between Unstable Housing, Food Insecurity, and Vision Status in the MI-SIGHT Community Eye Disease Screening Program.},
journal = {Ophthalmology},
volume = {131},
number = {2},
pages = {140-149},
pmid = {37709171},
issn = {1549-4713},
support = {K12 GM111725/GM/NIGMS NIH HHS/United States ; K23 MD016430/MD/NIMHD NIH HHS/United States ; U01 DP006442/DP/NCCDPHP CDC HHS/United States ; },
mesh = {Adult ; Humans ; Male ; Middle Aged ; Female ; Quality of Life ; Cross-Sectional Studies ; Housing ; *Refractive Errors ; *Vision, Low/complications ; Food Insecurity ; Prevalence ; Vision Disorders ; },
abstract = {PURPOSE: Housing and food insecurity are social risk factors that can impact eye health outcomes. This study investigated the association of these social risk factors with vision and ophthalmic pathologic characteristics.<br><br>DESIGN: Cross-sectional study from July 28, 2020, through July 27, 2021, for the free clinic and January 27, 2021, through January 26, 2022, for the Federally Qualified Health Center.<br><br>PARTICIPANTS: Michigan Screening and Intervention for Glaucoma and Eye Health through Telemedicine program first-year participants.<br><br>METHODS: Data collected included sociodemographic features, housing and food insecurity status, and results from a comprehensive telemedicine assessment. Individual-level and neighborhood-level characteristics were summarized with descriptive statistics. Differences in participant characteristics between housing and food security status were tested by 2-sample t tests for continuous measures and chi-square or Fisher exact tests for categorical measures. Logistic regression was used to test the independent associations between housing and food insecurity and ophthalmic disease, adjusted for age. The Holm&#x2019;s procedure was performed to adjust for multiple comparisons.<br><br>MAIN OUTCOME MEASURES: Visual impairment (VI; presenting visual acuity [VA], < 20/40), uncorrected or undercorrected refractive error (PVA, < 20/40; and best-corrected VA, &#x2265; 20/40), glaucoma, diabetic retinopathy, cataract, and macular degeneration.<br><br>RESULTS: Participants (n = 1165) were mean &#xb1; standard deviation [SD] of 55 &#xb1; 14.5 years of age, 62% identified as female, 54% identified as Black or African American, 10% identified as Hispanic or Latino, 49.7% had annual household income of less than $20 000, and 20% reported no medical insurance. Presenting VA was mean &#xb1; SD of 0.12 &#xb1; 0.19 logarithm of the minimum angle of resolution units (Snellen equivalent, 20/26 &#xb1; 1.9 lines). Visual impairment and uncorrected or undercorrected refractive error were identified in 10.3% and 8.3% of participants, respectively. Participants reported housing insecurity (3.4%) and food insecurity (28.9%), and 2.2% reported both. Among participants with unstable housing, 26.3% showed VI and 23.7% showed uncorrected or undercorrected refractive error. Unstable housing was associated with higher odds of VI (odds ratio, 3.53; P = 0.006) and uncorrected or undercorrected refractive error (odds ratio, 3.74; P = 0.006). No associations were observed between unstable housing and other ocular pathologic features or food insecurity and any ocular pathologic features.<br><br>CONCLUSIONS: Because unstable housing is associated with VI and uncorrected refractive error, future initiatives could focus on interventions to address both unstable housing and the increased need for eye care among those with unstable housing.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37708070,
year = {2023},
author = {Perron, A and Mandal, S and Chuba, TN and Mao, D and Singh, VP and Noda, N and Tan, R and Vu, HT and Abo, M and Uesugi, M},
title = {Small-Molecule Drug Repurposing for Counteracting Phototoxic A2E Aggregation.},
journal = {ACS chemical biology},
volume = {18},
number = {10},
pages = {2170-2175},
doi = {10.1021/acschembio.3c00339},
pmid = {37708070},
issn = {1554-8937},
mesh = {Humans ; *Retinal Pigment Epithelium/chemistry/metabolism/pathology ; Drug Repositioning ; Retinoids/metabolism ; *Macular Degeneration/etiology/metabolism/pathology ; },
abstract = {Despite the well-established role of oxidative stress in the pathogenesis of age-related macular degeneration (AMD), the mechanism underlying phototoxicity remains unclear. Herein, we used a drug repurposing approach to isolate an FDA-approved drug that blocks the aggregation of the photoinducible major fluorophore of lipofuscin, the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). Our fluorescence-based screening combined with dynamic light scattering (DLS) analysis led to the identification of entacapone as a potent inhibitor of A2E fluorescence and aggregation. The entacapone-mediated inhibition of A2E aggregation blocks its photodegradation and offers photoprotection in A2E-loaded retinal pigment epithelial (RPE) cells exposed to blue light. In-depth mechanistic analysis suggests that entacapone prevents the conversion of toxic aggregates by redirecting A2E into off-pathway oligomers. These findings provide evidence that aggregation contributes to the phototoxicity of A2E.},
}
@article {pmid37707890,
year = {2023},
author = {Gupta, AK and Meng, R and Modi, YS and Srinivasan, VJ},
title = {Imaging human macular pigments with visible light optical coherence tomography and superluminescent diodes.},
journal = {Optics letters},
volume = {48},
number = {18},
pages = {4737-4740},
pmid = {37707890},
issn = {1539-4794},
support = {R01 EB029747/EB/NIBIB NIH HHS/United States ; R01 EY031469/EY/NEI NIH HHS/United States ; R01 NS094681/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence ; *Macular Pigment ; Light ; Retina/diagnostic imaging ; },
abstract = {We demonstrate superluminescent diodes (SLDs) for visible light optical coherence tomography (OCT) of the human retina. SLDs are less costly than supercontinuum sources and have lower intrinsic excess noise, enabling imaging closer to the shot noise limit. While single SLDs are not broadband, they provide power concentrated at specific wavelengths relevant to retinal function. As a new, to the best of our knowledge, application, we image human macular pigments (MPs), which are thought to both aid vision and protect against advanced age-related macular degeneration. Using the unique depth-resolved capabilities of OCT, we localize MPs in depth to Henle's fibers beneath the foveal pit in the living human retina. Our approach reduces the cost of visible light OCT to nearly that of near-infrared (NIR) OCT while also providing information about clinically relevant MPs which cannot be measured in the NIR.},
}
@article {pmid37706090,
year = {2023},
author = {Ebert, JJ and Shildkrot, YE and Menezes, A and Miller, DM},
title = {Modified Split-Thickness Corneal Patch Graft for Conjunctival Erosions in Patients With the Port Delivery System Implant: Surgical Technique and Long-Term Outcomes.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {5},
pages = {420-423},
pmid = {37706090},
issn = {2474-1272},
abstract = {Purpose: To describe the surgical technique and long-term outcomes of a modified split-thickness corneal patch grafting for conjunctival erosions that can be seen in patients with the Port Delivery System (PDS) implant. Methods: By way of retrospective review of medical records, this interventional case series identified 2 cases in which modified split-thickness corneal patch grafting was used to repair conjunctival erosion in patients with the PDS implant. Results: The surgical approach involved creating a small opening in the corneal graft over the center of the PDS implant to improve visibility and allow for easier access during subsequent refill-exchange procedures. At the last follow-up of 6.9 years and 5.6 years, there was no recurrence of conjunctival erosions in either patient. The PDS implants remained well covered with the split-thickness corneal graft and had undergone multiple implant refills without complication or difficulty. Conclusions: Modified split-thickness corneal patch grafting with central graft aperture offers another option for long-term successful management of conjunctival erosions in patients with a PDS, especially those who have failed prior repair, by allowing sufficient visibility and access for subsequent refill-exchange procedures.},
}
@article {pmid37705880,
year = {2023},
author = {Alrobaian, M},
title = {Pegylated nanoceria: A versatile nanomaterial for noninvasive treatment of retinal diseases.},
journal = {Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society},
volume = {31},
number = {10},
pages = {101761},
pmid = {37705880},
issn = {1319-0164},
abstract = {Oxidative stress induced reactive oxygen species has been implicated as the primary molecular mechanism in the pathogenesis of debilitating retinal diseases such as diabetic retinopathy, neovascularization and age-related macular degeneration. Nanoceria (cerium oxide nanoparticles) has recently received much attention, because of its superior and regenerative radical scavenging properties. This review focuses on retinal applications of nanoceria and functionalized nanoceria. Studies in animal models showed that nanoceria possess antioxidant, anti-inflammatory, anti-angiogenic, anti-apoptotic properties and preserves retinal morphology and prevents loss of retinal functions. Nanoceria have been tested in animal models of age-related macular degeneration and neovascularization and their efficacy have been shown to persist for a long time, without any collateral effects. To date, several pharmaceutical formulations of nanoceria have been developed for their prospective clinical ophthalmic applications such as chitosan coated nanoceria, nanoceria loaded into hydrogels, nanoceria embedded in wafers and contact lens and organosilane or polyethylene glycol functionalized nanoceria. Based on their nano size range, ocular permeation could be achieved to allow topical administration of nanoceria. PEGylation of nanoceria represents the key strategy to support eye drop formulation with enhanced corneal permeation, without altering chemical physical properties. Based on their excellent antioxidant properties, nano-size, safety and tolerability, PEGylated nanoceria represent a new potential therapeutic for the treatment.},
}
@article {pmid37705491,
year = {2023},
author = {Xu, S and Cui, K and Long, K and Li, J and Fan, N and Lam, WC and Liang, X and Wang, W},
title = {Red Light-Triggered Anti-Angiogenic and Photodynamic Combination Therapy of Age-Related Macular Degeneration.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {10},
number = {31},
pages = {e2301985},
pmid = {37705491},
issn = {2198-3844},
support = {82&#xa0;222&#xa0;903//National Natural Science Foundation of China/ ; 82&#xa0;271&#xa0;099//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Reactive Oxygen Species/therapeutic use ; *Porphyrins ; *Photochemotherapy ; Verteporfin/therapeutic use ; *Macular Degeneration/drug therapy/pathology ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; },
abstract = {Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti-angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less-invasive approach is reported to achieve anti-angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem is self-assembled by reactive oxygen species (ROS)-sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red-light irradiation to the diseased eyes, intraocular release of anti-angiogenic DAS is observed, together with selective neo-vessels occlusion by VER-generated ROS. Notably, Di-DAS-VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem.},
}
@article {pmid37704835,
year = {2023},
author = {Ajgaonkar, BS and Kumaran, A and Kumar, S and Jain, RD and Dandekar, PP},
title = {Cell-based Therapies for Corneal and Retinal Disorders.},
journal = {Stem cell reviews and reports},
volume = {19},
number = {8},
pages = {2650-2682},
pmid = {37704835},
issn = {2629-3277},
support = {IF200203//Department of Science and Technology, Government of Rajasthan/ ; },
mesh = {Humans ; Cornea ; Cell- and Tissue-Based Therapy ; *Retinal Degeneration ; Retina ; *Corneal Diseases/therapy ; },
abstract = {Maintenance of the visual function is the desired outcome of ophthalmologic therapies. The shortcomings of the current treatment options, like partial recovery, post-operation failure, rigorous post-operative care, complications, etc., which are usually encountered with the conventional treatment options has warranted newer treatment options that may eliminate the root cause of diseases and minimize the side effects. Cell therapies, a class of regenerative medicines, have emerged as cutting-edge treatment option. The corneal and retinal dystrophies during the ocular disorders are the major cause of blindness, worldwide. Corneal disorders are mainly categorized mainly into corneal epithelial, stromal, and endothelial disorders. On the other hand, glaucoma, retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, Stargardt Disease, choroideremia, Leber congenital amaurosis are then major retinal degenerative disorders. In this manuscript, we have presented a detailed overview of the development of cell-based therapies, using embryonic stem cells, bone marrow stem cells, mesenchymal stem cells, dental pulp stem cells, induced pluripotent stem cells, limbal stem cells, corneal epithelial, stromal and endothelial, embryonic stem cell-derived differentiated cells (like retinal pigment epithelium or RPE), neural progenitor cells, photoreceptor precursors, and bone marrow-derived hematopoietic stem/progenitor cells etc. The manuscript highlights their efficiency, drawbacks and the strategies that have been explored to regain visual function in the preclinical and clinical state associated with them which can be considered for their potential application in the development of treatment.},
}
@article {pmid37704045,
year = {2023},
author = {Guo, D and Qi, J and Du, Y and Zhao, C and Liu, S and Lu, Y and Zhu, X},
title = {Tear inflammatory cytokines as potential biomarkers for myopic macular degeneration.},
journal = {Experimental eye research},
volume = {235},
number = {},
pages = {109648},
doi = {10.1016/j.exer.2023.109648},
pmid = {37704045},
issn = {1096-0007},
mesh = {Humans ; Cytokines ; Interleukin-6 ; Case-Control Studies ; *Myopia, Degenerative/diagnosis ; *Macular Degeneration/diagnosis ; Biomarkers ; Fundus Oculi ; },
abstract = {Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there has been currently no study revealing the levels of inflammatory cytokines in tear. Therefore, this study aimed to determine tear cytokine levels of highly myopic eyes, and their relationships with myopic macular degeneration (MMD). This case-control study screened inflammatory cytokines of tear samples from 132 highly myopic and 105 emmetropic eyes using a multiplex cytokine antibody array, and cytokines showing significant intergroup differences were further validated using ProQuantum immunoassays in tear samples from another 60 highly myopic and 60 emmetropic eyes. Ultra-widefield fundus photographs of eyes were classified according to the meta-analyses of the Pathologic Myopia Classification. Associations between tear cytokine levels and MMD category were investigated. As a result, tear levels of interleukin (IL)-6, IL-13 and monocyte chemoattractant protein (MCP)-1 were screened significantly higher in highly myopic eyes than in emmetropic controls (IL-6: 11.70 ± 16.81 versus 8.22 ± 10.76 pg/mL; MCP-1: 63.60 ± 54.40 versus 33.87 ± 43.82 pg/mL; both P < 0.05). Validation assays further demonstrated the elevated concentrations of IL-6 and MCP-1 (IL-6: 13.97 ± 8.41 versus 8.06 ± 7.94 pg/mL, P < 0.001; MCP-1: 32.69 ± 8.41 versus 18.07 ± 8.41 pg/mL, P = 0.003). Tear levels of IL-6 and MCP-1 differed significantly among MMD categories (both P < 0.05). The area under receiver operating characteristic curve were 0.783 and 0.682 respectively (both P < 0.05), when using tear IL-6 and MCP-1 levels to predict the presence of MMD (category ≥2). The ordered logistic regression model also indicated that longer axial length, and higher IL-6 and MCP-1 tear levels were independent predictors of higher MMD category. In our study, highly myopic eyes presented significantly higher levels of tear IL-6 and MCP-1, which may also serve as potential biomarkers for MMD.},
}
@article {pmid37703839,
year = {2023},
author = {Borrelli, E and Berni, A and Mastropasqua, L and Querques, G and Sadda, SR and Sarraf, D and Bandello, F},
title = {Pushing Retinal Imaging Forward: Innovations and Their Clinical Meaning - The 2022 Ophthalmologica Lecture.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {5-6},
pages = {278-294},
doi = {10.1159/000533910},
pmid = {37703839},
issn = {1423-0267},
mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; Cross-Sectional Studies ; *Macular Edema/pathology ; Retina/pathology ; *Central Serous Chorioretinopathy ; *Macular Degeneration/pathology ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; },
abstract = {Retinal imaging has greatly expanded our understanding of various pathological conditions. This article presents a summary of the key points covered during the 2022 Ophthalmologica Lecture held at the Euretina Congress in Hamburg. The first part of the article focuses on the use of optical coherence tomography angiography to examine and comprehend the choroid in age-related macular degeneration (AMD). Subsequently, we delve into the discussion of the "postreceptor neuronal loss" theory in AMD, which was studied using en face structural optical coherence tomography (OCT). Following that, we explore pertinent findings obtained through cross-sectional OCT in retinal and optic nerve diseases, such as AMD, diabetic macular edema, pathologic myopia, central serous chorioretinopathy, and Leber's hereditary optic neuropathy.},
}
@article {pmid37702300,
year = {2023},
author = {Evans, JR and Lawrenson, JG},
title = {Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration.},
journal = {The Cochrane database of systematic reviews},
volume = {9},
number = {9},
pages = {CD000254},
pmid = {37702300},
issn = {1469-493X},
mesh = {Male ; Female ; Humans ; Antioxidants/therapeutic use ; Vitamins/therapeutic use ; *Geographic Atrophy/prevention &amp; control ; beta Carotene ; Lutein/therapeutic use ; Zeaxanthins/therapeutic use ; Minerals ; Dietary Supplements ; *Macular Degeneration/epidemiology/prevention &amp; control ; Vitamin A ; Vitamin K ; Zinc ; *Malnutrition ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a degenerative condition of the back of the eye that occurs in people over the age of 50 years. Antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of AMD. This is the third update of the review.<br><br>OBJECTIVES: To assess the effects of antioxidant vitamin and mineral supplements on the progression of AMD in people with AMD.<br><br>SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and three trials registers, most recently on 29 November 2022.<br><br>SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation to placebo or no intervention, in people with AMD.<br><br>DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane.<br><br>MAIN RESULTS: We included 26 studies conducted in the USA, Europe, China, and Australia. These studies enroled 11,952 people aged 65 to 75 years and included slightly more women (on average 56% women). We judged the studies that contributed data to the review to be at low or unclear risk of bias. Thirteen studies compared multivitamins with control in people with early and intermediate AMD. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 3 studies, 2445 participants; moderate-certainty evidence). In people with early AMD, who are at low risk of progression, this means there would be approximately four fewer cases of progression to late AMD for every 1000 people taking vitamins (one fewer to six fewer cases). In people with intermediate AMD at higher risk of progression, this corresponds to approximately 78 fewer cases of progression for every 1000 people taking vitamins (26 fewer to 126 fewer). AREDS also provided evidence of a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence), and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (measured with the Visual Function Questionnaire) in treated compared with non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). In exploratory subgroup analyses in the follow-on study to AREDS (AREDS2), replacing beta-carotene with lutein/zeaxanthin gave hazard ratios (HR) of 0.82 (95% CI 0.69 to 0.96), 0.78 (95% CI 0.64 to 0.94), 0.94 (95% CI 0.70 to 1.26), and 0.88 (95% CI 0.75 to 1.03) for progression to late AMD, neovascular AMD, geographic atrophy, and vision loss, respectively. Six studies compared lutein (with or without zeaxanthin) with placebo and one study compared a multivitamin including lutein/zeaxanthin with multivitamin alone. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA; almost all participants in AREDS2 also took the original AREDS supplementation formula. People taking lutein/zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05) compared with control (1 study, 4176 participants, 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein/zeaxanthin and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (Visual Function Questionnaire) was similar between groups (MD 1.21, 95% CI -2.59 to 5.01; 2 studies, 308 participants; moderate-certainty evidence). One study in Australia randomised 1204 people to vitamin E or placebo with four years of follow-up; 19% of participants had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05; very low-certainty evidence). There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47; low-certainty evidence). There were no data on neovascular AMD, geographic atrophy, or quality of life. Five studies compared zinc with placebo. Evidence largely drawn from the largest study (AREDS) found a lower progression to late AMD over six years (OR 0.83, 95% CI 0.70 to 0.98; 3 studies, 3790 participants; moderate-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 2 studies, 3791 participants; moderate-certainty evidence). There were no data on quality of life. Gastrointestinal symptoms were the main reported adverse effect. In AREDS, zinc was associated with a higher risk of genitourinary problems in men, but no difference was seen between high- and low-dose zinc groups in AREDS2. Most studies were too small to detect rare adverse effects. Data from larger studies (AREDS/AREDS2) suggested there may be little or no effect on mortality with multivitamin (HR 0.87, 95% CI 0.60 to 1.25; low-certainty evidence) or lutein/zeaxanthin supplementation (HR 1.06, 95% CI 0.87 to 1.31; very low-certainty evidence), but confirmed the increased risk of lung cancer with beta-carotene, mostly in former smokers.<br><br>AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that antioxidant vitamin and mineral supplementation (AREDS: vitamin C, E, beta-carotene, and zinc) probably slows down progression to late AMD. People with intermediate AMD have a higher chance of benefiting from antioxidant supplements because their risk of progression is higher than people with early AMD. Although low-certainty evidence suggested little effect with lutein/zeaxanthin alone compared with placebo, exploratory subgroup analyses from one large American study support the view that lutein/zeaxanthin may be a suitable replacement for the beta-carotene used in the original AREDS formula.},
}
@article {pmid37701269,
year = {2023},
author = {Nguyen, AH and Davoudi, S and Dong, K and Bains, A and Ness, S and Subramanian, ML and Siegel, NH and Chen, X},
title = {Socioeconomic Disparities in Patients Receiving Intravitreal Injections for Age-Related Macular Degeneration Amid the COVID-19 Pandemic.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {5},
pages = {376-381},
pmid = {37701269},
issn = {2474-1272},
abstract = {Purpose: To determine the effects of socioeconomic factors on visit adherence and the resultant visual outcomes for patients receiving intravitreal injections for neovascular age-related macular degeneration during the COVID-19 pandemic. Methods: In this retrospective case-control study, medical records were reviewed to collect appointment attendance, age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, and Area Deprivation Index (ADI), a measure of socioeconomic disadvantage. Multivariate regression models were created to determine differences in socioeconomic factors between individuals who attended (show group) and those who did not attend (no-show group) appointments. Results: The study enrolled 126 patients in the show group and 115 in the no-show group. On univariate analysis, nonadherence was significantly higher in non-White patients than in White patients (P = .04), urban sites than in suburban sites (P = 1.7 × 10[-4]), and non-English-speaking patients than in English-speaking patients (P = 4.0 × 10[-3]). The associations remained significant in multivariate analysis for non-English-speaking patients (P = .03) and urban-site patients (P = .01) after adjusting for age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, site of visit, and ADI. At 6 months and 1 year, a 1-, 2-, and 3-line vision loss was significantly higher in the no-show group than in the show group on univariate and multivariate analysis after adjusting for age, sex, race, lens status, and presence of glaucoma and diabetic retinopathy. Conclusions: Non-English-speaking patients and urban-based patients were less likely to present for intravitreal injection appointments during the initial peak of the COVID-19 pandemic. This disparity translated to worse vision outcomes at 6 months and 1 year.},
}
@article {pmid37698269,
year = {2024},
author = {Barequet, D and Shor, R and Segal, O and Greenbaum, E and Trivizki, O and Loewenstein, A and Rabina, G},
title = {Treatment patterns and visual acuity change of AMD patients, before, during and after the COVID-19 pandemic lockdowns: A large cohort.},
journal = {Acta ophthalmologica},
volume = {102},
number = {3},
pages = {e322-e327},
doi = {10.1111/aos.15756},
pmid = {37698269},
issn = {1755-3768},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Pandemics ; *COVID-19/epidemiology ; Communicable Disease Control ; Intravitreal Injections ; Visual Acuity ; Ranibizumab ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To evaluate the impact of the changes in treatment patterns before, during and after the COVID-19 pandemic on best-corrected visual acuity (BCVA) in previously treated neovascular age-related macular degeneration (nAMD) patients.<br><br>METHODS: A multi-centre, retrospective, observational study of consecutive nAMD patients during 2019-2021. Data collected included demographics, BCVA, dates of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and clinic visits.<br><br>RESULTS: A total of 1652 eyes of 1652 nAMD patients were included, out of which 850 eyes were assessed in 2019 (pre-COVID-19), 630 eyes were assessed in 2020 (COVID-19) and 974 eyes were assessed in 2021 (post-COVID-19). During the COVID-19 period, the mean number of anti-VEGF injections was significantly lower than the corresponding pre-COVID-19 and post-COVID-19 periods (5.55 compared to 6.13 and 6.60, respectively p&#x2009;<&#x2009;0.01). A constant lower ratio of injections per patient/month was observed during COVID-19 compared to previous and following years, with a notable decline during March-April, reaching a ratio of 0.4 in 2020 versus 0.65 in 2019 and 0.62 in 2021 (p&#x2009;<&#x2009;0.01). Baseline BCVA (0.825, p&#x2009;<&#x2009;0.001), number of injections (-0.007, p&#x2009;<&#x2009;0.001), gender (-0.027, p&#x2009;=&#x2009;0.037) and age (0.004, p&#x2009;<&#x2009;0.001) were shown to be significant predictors of final BCVA.<br><br>CONCLUSION: During the COVID-19 period, patients were treated with significantly less intravitreal anti-VEGF injection compared to the previous year with compensation in the following year. These changes in treatment patterns did not have a significant impact on BCVA outcomes. Age, gender, baseline BCVA and number of injections are predictors of final visual outcomes.},
}
@article {pmid37696869,
year = {2023},
author = {Fan, Q and Li, H and Wang, X and Tham, YC and Teo, KYC and Yasuda, M and Lim, WK and Kwan, YP and Teo, JX and Chen, CJ and Chen, LJ and Ahn, J and Davila, S and Miyake, M and Tan, P and Park, KH and Pang, CP and Khor, CC and Wong, TY and Yanagi, Y and Cheung, CMG and Cheng, CY},
title = {Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {5574},
pmid = {37696869},
issn = {2041-1723},
mesh = {Aged ; Animals ; Humans ; Mice ; Asian ; East Asian People ; Extracellular Matrix/genetics ; Genome-Wide Association Study ; *Macular Degeneration/genetics ; *Polypoidal Choroidal Vasculopathy/genetics ; Disease Models, Animal ; },
abstract = {Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ([Formula: see text]). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; [Formula: see text]) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.},
}
@article {pmid37696275,
year = {2023},
author = {Khanani, AM and Patel, SS and Staurenghi, G and Tadayoni, R and Danzig, CJ and Eichenbaum, DA and Hsu, J and Wykoff, CC and Heier, JS and Lally, DR and Monés, J and Nielsen, JS and Sheth, VS and Kaiser, PK and Clark, J and Zhu, L and Patel, H and Tang, J and Desai, D and Jaffe, GJ and , },
title = {Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial.},
journal = {Lancet (London, England)},
volume = {402},
number = {10411},
pages = {1449-1458},
doi = {10.1016/S0140-6736(23)01583-0},
pmid = {37696275},
issn = {1474-547X},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Complement Inactivating Agents/therapeutic use ; Double-Blind Method ; *Geographic Atrophy/drug therapy ; *Intravitreal Injections ; Treatment Outcome ; *Visual Acuity/drug effects ; *Aptamers, Nucleotide/therapeutic use ; *Polyethylene Glycols/therapeutic use ; Organic Chemicals ; },
abstract = {BACKGROUND: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth.<br><br>METHODS: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 &#x3bc;L intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366.<br><br>FINDINGS: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0&#xb7;336 mm/year (SE 0&#xb7;032) with avacincaptad pegol 2 mg and 0&#xb7;392 mm/year (0&#xb7;033) with sham, a difference in growth of 0&#xb7;056 mm/year (95% CI 0&#xb7;016-0&#xb7;096; p=0&#xb7;0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group.<br><br>INTERPRETATION: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy.<br><br>FUNDING: Iveric Bio, An Astellas Company.},
}
@article {pmid37693625,
year = {2023},
author = {Grunin, M and Igo, RP and Song, YE and Blanton, SH and Pericak-Vance, MA and Haines, JL and , },
title = {Identifying X-Chromosome Variants Associated with Age-Related Macular Degeneration.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.08.28.23294688},
pmid = {37693625},
abstract = {PURPOSE: In genome-wide association studies (GWAS), X chromosome (ChrX) variants are often not investigated. Sex-specific effects and ChrX-specific quality control (QC) are needed to examine these effects. Previous analyses identified 52 autosomal variants associated with age-related macular degeneration (AMD) via the International AMD Genomics Consortium (IAMDGC), but did not analyze ChrX. Therefore, our goal was to investigate ChrX variants for association with AMD.<br><br>METHODS: We genotyped 29,629 non-Hispanic White (NHW) individuals (M/F:10,404/18,865; AMD12,087/14723) via a custom chip and imputed after ChrX-specific QC (XWAS 3.0) using the Michigan Imputation Server. Imputation generated 1,221,623 variants on ChrX. Age, informative PCs, and subphenotyeps were covariates for logistic association analyses with Fishers correction. Gene/pathway analyses were performed with VEGAS, GSEASNP, ICSNPathway, DAVID, and mirPath.<br><br>RESULTS: Logistic association on NHW individuals with sex correction, identified variants in/near the genes SLITRK4, ARHGAP6, FGF13 and DMD associated with AMD (P<1x10 [-6] ,Fishers combined-corrected). Via association testing of subphenotypes of choroidal neovascularization and geographic atrophy (GA), variants in DMD associated with GA (P<1x10 [-6] , Fishers combined-corrected). Via gene-based analysis with VEGAS, several genes were associated with AMD (P<0.05, both truncated tail strength/truncated product P) including SLITRK4 and BHLHB9 . Pathway analysis using GSEASNP and DAVID showed genes associated with nervous system development (FDR: P:0.02), and blood coagulation (FDR: P:0.03). Variants in the region of a microRNA (miR) were associated with AMD (P<0.05, truncated tail strength/truncated product P). Via DIANA mirPath analysis, downstream targets of miRs show association with brain disorders and fatty acid elongation (P<0.05). A long-non coding RNA on ChrX near the DMD locus was also associated with AMD (P=4x10 [-7]). Epistatic analysis (t-statistic) for a quantitative trait of AMD vs control including covariates found a suggestive association in the XG gene (P=2x10^-5).<br><br>CONCLUSIONS: Analysis of ChrX variants demonstrates association with AMD and these variants may be linked to novel pathways. Further analysis is needed to confirm results and to understand their biological significance and relationship with AMD development in worldwide populations.},
}
@article {pmid37693462,
year = {2023},
author = {Grunin, M and de Jong, S and Palmer, EL and Jin, B and Rinker, D and Moth, C and Capra, A and Haines, JL and Bush, WS and den Hollander, AI and , },
title = {Spatial Distribution of Missense Variants within Complement Proteins Associates with Age Related Macular Degeneration.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.08.28.23294686},
pmid = {37693462},
abstract = {PURPOSE: Genetic variants in complement genes are associated with age-related macular degeneration (AMD). However, many rare variants have been identified in these genes, but have an unknown significance, and their impact on protein function and structure is still unknown. We set out to address this issue by evaluating the spatial placement and impact on protein structureof these variants by developing an analytical pipeline and applying it to the International AMD Genomics Consortium (IAMDGC) dataset (16,144 AMD cases, 17,832 controls).<br><br>METHODS: The IAMDGC dataset was imputed using the Haplotype Reference Consortium (HRC), leading to an improvement of over 30% more imputed variants, over the original 1000 Genomes imputation. Variants were extracted for the CFH , CFI , CFB , C9 , and C3 genes, and filtered for missense variants in solved protein structures. We evaluated these variants as to their placement in the three-dimensional structure of the protein (i.e. spatial proximity in the protein), as well as AMD association. We applied several pipelines to a) calculate spatial proximity to known AMD variants versus gnomAD variants, b) assess a variant's likelihood of causing protein destabilization via calculation of predicted free energy change (ddG) using Rosetta, and c) whole gene-based testing to test for statistical associations. Gene-based testing using seqMeta was performed using a) all variants b) variants near known AMD variants or c) with a ddG >|2|. Further, we applied a structural kernel adaptation of SKAT testing (POKEMON) to confirm the association of spatial distributions of missense variants to AMD. Finally, we used logistic regression on known AMD variants in CFI to identify variants leading to >50% reduction in protein expression from known AMD patient carriers of CFI variants compared to wild type (as determined by in vitro experiments) to determine the pipeline's robustness in identifying AMD-relevant variants. These results were compared to functional impact scores, ie CADD values > 10, which indicate if a variant may have a large functional impact genomewide, to determine if our metrics have better discriminative power than existing variant assessment methods. Once our pipeline had been validated, we then performed a priori selection of variants using this pipeline methodology, and tested AMD patient cell lines that carried those selected variants from the EUGENDA cohort (n=34). We investigated complement pathway protein expression in vitro , looking at multiple components of the complement factor pathway in patient carriers of bioinformatically identified variants.<br><br>RESULTS: Multiple variants were found with a ddG>|2| in each complement gene investigated. Gene-based tests using known and novel missense variants identified significant associations of the C3 , C9 , CFB , and CFH genes with AMD risk after controlling for age and sex (P=3.22&#xd7;10 [-5] ;7.58&#xd7;10 [-6] ;2.1&#xd7;10 [-3] ;1.2&#xd7;10 [-31]). ddG filtering and SKAT-O tests indicate that missense variants that are predicted to destabilize the protein, in both CFI and CFH, are associated with AMD (P=CFH:0.05, CFI:0.01, threshold of 0.05 significance). Our structural kernel approach identified spatial associations for AMD risk within the protein structures for C3, C9, CFB, CFH, and CFI at a nominal p-value of 0.05. Both ddG and CADD scores were predictive of reduced CFI protein expression, with ROC curve analyses indicating ddG is a better predictor (AUCs of 0.76 and 0.69, respectively). A priori in vitro analysis of variants in all complement factor genes indicated that several variants identified via bioinformatics programs PathProx/POKEMON in our pipeline via in vitro experiments caused significant change in complement protein expression (P=0.04) in actual patient carriers of those variants, via ELISA testing of proteins in the complement factor pathway, and were previously unknown to contribute to AMD pathogenesis.<br><br>CONCLUSION: We demonstrate for the first time that missense variants in complement genes cluster together spatially and are associated with AMD case/control status. Using this method, we can identify CFI and CFH variants of previously unknown significance that are predicted to destabilize the proteins. These variants, both in and outside spatial clusters, can predict in-vitro tested CFI protein expression changes, and we hypothesize the same is true for CFH . A priori identification of variants that impact gene expression allow for classification for previously classified as VUS. Further investigation is needed to validate the models for additional variants and to be applied to all AMD-associated genes.},
}
@article {pmid37693313,
year = {2023},
author = {Zhang, Q and Bhatia, M and Park, T and Ott, J},
title = {A multi-threaded approach to genotype pattern mining for detecting digenic disease genes.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1222517},
pmid = {37693313},
issn = {1664-8021},
abstract = {To locate disease-causing DNA variants on the human gene map, the customary approach has been to carry out a genome-wide association study for one variant after another by testing for genotype frequency differences between individuals affected and unaffected with disease. So-called digenic traits are due to the combined effects of two variants, often on different chromosomes, while individual variants may have little or no effect on disease. Machine learning approaches have been developed to find variant pairs underlying digenic traits. However, many of these methods have large memory requirements so that only small datasets can be analyzed. The increasing availability of desktop computers with large numbers of processors and suitable programming to distribute the workload evenly over all processors in a machine make a new and relatively straightforward approach possible, that is, to evaluate all existing variant and genotype pairs for disease association. We present a prototype of such a method with two components, Vpairs and Gpairs, and demonstrate its advantages over existing implementations of such well-known algorithms as Apriori and FP-growth. We apply these methods to published case-control datasets on age-related macular degeneration and Parkinson disease and construct an ROC curve for a large set of genotype patterns.},
}
@article {pmid37692378,
year = {2023},
author = {Swain, TA and McGwin, G and Owsley, C},
title = {Re: Higgins et al.: Assessment of the classification of age-related macular degeneration severity from the Northern Ireland Sensory Ageing Study using a measure of dark adaptation (Ophthalmol Sci. 2023;3(2):100204).},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100376},
pmid = {37692378},
issn = {2666-9145},
}
@article {pmid37691820,
year = {2023},
author = {Jones, MK and Orozco, LD and Qin, H and Truong, T and Caplazi, P and Elstrott, J and Modrusan, Z and Chaney, SY and Jeanne, M},
title = {Integration of human stem cell-derived in vitro systems and mouse preclinical models identifies complex pathophysiologic mechanisms in retinal dystrophy.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1252547},
pmid = {37691820},
issn = {2296-634X},
abstract = {Rare DRAM2 coding variants cause retinal dystrophy with early macular involvement via unknown mechanisms. We found that DRAM2 is ubiquitously expressed in the human eye and expression changes were observed in eyes with more common maculopathy such as Age-related Macular Degeneration (AMD). To gain insights into pathogenicity of DRAM2-related retinopathy, we used a combination of in vitro and in vivo models. We found that DRAM2 loss in human pluripotent stem cell (hPSC)-derived retinal organoids caused the presence of additional mesenchymal cells. Interestingly, Dram2 loss in mice also caused increased proliferation of cells from the choroid in vitro and exacerbated choroidal neovascular lesions in vivo. Furthermore, we observed that DRAM2 loss in human retinal pigment epithelial (RPE) cells resulted in increased susceptibility to stress-induced cell death in vitro and that Dram2 loss in mice caused age-related photoreceptor degeneration. This highlights the complexity of DRAM2 function, as its loss in choroidal cells provided a proliferative advantage, whereas its loss in post-mitotic cells, such as photoreceptor and RPE cells, increased degeneration susceptibility. Different models such as human pluripotent stem cell-derived systems and mice can be leveraged to study and model human retinal dystrophies; however, cell type and species-specific expression must be taken into account when selecting relevant systems.},
}
@article {pmid37691588,
year = {2023},
author = {Shughoury, A and Sevgi, DD and Ciulla, TA},
title = {The complement system: a novel therapeutic target for age-related macular degeneration.},
journal = {Expert opinion on pharmacotherapy},
volume = {24},
number = {17},
pages = {1887-1899},
doi = {10.1080/14656566.2023.2257604},
pmid = {37691588},
issn = {1744-7666},
mesh = {Humans ; *Macular Degeneration/drug therapy/metabolism ; *Geographic Atrophy/drug therapy/etiology/metabolism ; Immunologic Factors/therapeutic use ; Therapies, Investigational ; Pharmaceutical Preparations ; },
abstract = {INTRODUCTION: With the recent FDA approvals of pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals) and avacincaptad pegol (IZERVAY, Astellas Pharmaceuticals), modulation of the complement system has emerged as a promising therapeutic approach for slowing progression of geographic atrophy (GA) in AMD.<br><br>AREAS COVERED: This article reviews the current understanding of the complement system, its role in AMD, and the various complement-targeting therapies in development for the treatment of GA, including monoclonal antibodies, aptamers, protein analogs, and gene therapies. Approved and investigational agents have largely focused on interfering with the activity of complement components 3 and 5, owing to their central roles in the classical, lectin, and alternative complement pathways. Other investigational therapies have targeted formation of membrane attack complex (a terminal step in the complement cascade which leads to cell lysis), complement factors H and I (which serve regulatory functions in the alternative pathway), complement factors B and D (within the alternative pathway), and complement component 1 (within the classical pathway). Clinical trials investigating these agents are summarized, and the potential benefits and limitations of these therapies are discussed.<br><br>EXPERT OPINION: Targeting the complement system is a promising therapeutic approach for slowing the progression of GA in AMD, potentially improving visual outcomes. However, increased risk of exudative conversion must be considered, and further research is required to identify clinical criteria and best practices for initiating complement inhibitor therapy for GA.},
}
@article {pmid37689221,
year = {2023},
author = {Chen, X and Chen, L and Lin, Y and Li, G},
title = {Causality of Diabetic Nephropathy and Age-Related Macular Degeneration: A Mendelian Randomization Study.},
journal = {Gene},
volume = {889},
number = {},
pages = {147787},
doi = {10.1016/j.gene.2023.147787},
pmid = {37689221},
issn = {1879-0038},
mesh = {Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Diabetic Nephropathies/genetics/complications ; Cholesterol, HDL ; Risk Factors ; Triglycerides ; *Macular Degeneration/genetics ; Polymorphism, Single Nucleotide ; *Diabetes Mellitus ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) currently stands as the leading cause of irreversible vision loss in the present era. The primary objective of this study was to investigate the causal relationships between diabetic nephropathy (DN), its associated risk factors, and AMD among participants of European descent.<br><br>METHODS: Genetic variants associated with DN and its risk factors, encompassing glycemic traits, lipidemic traits, systolic/diastolic blood pressure, obesity, and urate, were obtained from previously published genome-wide association studies. Summary-level statistics for AMD were acquired from the FinnGen database. Univariable and multivariable Mendelian randomization (MR) were employed to conduct this investigation.<br><br>RESULTS: Our MR analyses indicated that per 1-standard deviation (SD) increase of DN heightened the risk of overall AMD (p&#xa0;=&#xa0;1.03&#xa0;&#xd7;&#xa0;10[-8], OR&#xa0;=&#xa0;1.24). And these findings remained consistent when examining both dry AMD (p&#xa0;=&#xa0;2.27&#xa0;&#xd7;&#xa0;10[-4], OR&#xa0;=&#xa0;1.17) and wet AMD (p&#xa0;=&#xa0;5.15&#xa0;&#xd7;&#xa0;10[-6], OR&#xa0;=&#xa0;1.33). Additionally, there was a causal association between high-density lipoprotein-cholesterol (HDL-C) levels and an increased risk of AMD (p&#xa0;=&#xa0;2.69&#xa0;&#xd7;&#xa0;10[-3], OR&#xa0;=&#xa0;1.23), while triglycerides were found to mitigate the risk (p&#xa0;=&#xa0;0.02, OR&#xa0;=&#xa0;0.83). Notably, no significant associations were observed between other risk factors of DN and AMD.<br><br>CONCLUSIONS: These findings suggest that the impact of DN on the development of AMD may be more substantial than previously believed. Furthermore, elevated HDL-C levels appear to heighten the risk of AMD, whereas triglycerides may provide a protective effect.},
}
@article {pmid37687770,
year = {2023},
author = {Yu, YW and Lin, CH and Lu, CK and Wang, JK and Huang, TL},
title = {Automated Age-Related Macular Degeneration Detector on Optical Coherence Tomography Images Using Slice-Sum Local Binary Patterns and Support Vector Machine.},
journal = {Sensors (Basel, Switzerland)},
volume = {23},
number = {17},
pages = {},
pmid = {37687770},
issn = {1424-8220},
support = {MOST 110-2221-E-155-013//Ministry of Science and Technology, Taiwan/ ; MOST 111-2221-E-155-046-MY2//Ministry of Science and Technology, Taiwan/ ; },
mesh = {Humans ; *Artificial Intelligence ; Support Vector Machine ; Tomography, Optical Coherence ; Algorithms ; *Macular Degeneration/diagnostic imaging ; },
abstract = {Artificial intelligence has revolutionised smart medicine, resulting in enhanced medical care. This study presents an automated detector chip for age-related macular degeneration (AMD) using a support vector machine (SVM) and three-dimensional (3D) optical coherence tomography (OCT) volume. The aim is to assist ophthalmologists by reducing the time-consuming AMD medical examination. Using the property of 3D OCT volume, a modified feature vector connected method called slice-sum is proposed, reducing computational complexity while maintaining high detection accuracy. Compared to previous methods, this method significantly reduces computational complexity by at least a hundredfold. Image adjustment and noise removal steps are excluded for classification accuracy, and the feature extraction algorithm of local binary patterns is determined based on hardware consumption considerations. Through optimisation of the feature vector connection method after feature extraction, the computational complexity of SVM detection is significantly reduced, making it applicable to similar 3D datasets. Additionally, the design supports model replacement, allowing users to train and update classification models as needed. Using TSMC 40 nm CMOS technology, the proposed detector achieves a core area of 0.12 mm[2] while demonstrating a classification throughput of 8.87 decisions/s at a maximum operating frequency of 454.54 MHz. The detector achieves a final testing classification accuracy of 92.31%.},
}
@article {pmid37686457,
year = {2023},
author = {Wong, NK and Yip, SP and Huang, CL},
title = {Establishing Functional Retina in a Dish: Progress and Promises of Induced Pluripotent Stem Cell-Based Retinal Neuron Differentiation.},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
pages = {},
pmid = {37686457},
issn = {1422-0067},
support = {CEVR RP1.6//Health@InnoHK Fund, HKSAR Government/ ; },
mesh = {Animals ; Humans ; *Induced Pluripotent Stem Cells ; Retina ; *Retinal Neurons ; Cell Differentiation ; *Retinal Degeneration/therapy ; Blindness ; },
abstract = {The human eye plays a critical role in vision perception, but various retinal degenerative diseases such as retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD) can lead to vision loss or blindness. Although progress has been made in understanding retinal development and in clinical research, current treatments remain inadequate for curing or reversing these degenerative conditions. Animal models have limited relevance to humans, and obtaining human eye tissue samples is challenging due to ethical and legal considerations. Consequently, researchers have turned to stem cell-based approaches, specifically induced pluripotent stem cells (iPSCs), to generate distinct retinal cell populations and develop cell replacement therapies. iPSCs offer a novel platform for studying the key stages of human retinogenesis and disease-specific mechanisms. Stem cell technology has facilitated the production of diverse retinal cell types, including retinal ganglion cells (RGCs) and photoreceptors, and the development of retinal organoids has emerged as a valuable in vitro tool for investigating retinal neuron differentiation and modeling retinal diseases. This review focuses on the protocols, culture conditions, and techniques employed in differentiating retinal neurons from iPSCs. Furthermore, it emphasizes the significance of molecular and functional validation of the differentiated cells.},
}
@article {pmid37686143,
year = {2023},
author = {Campagnoli, LIM and Varesi, A and Barbieri, A and Marchesi, N and Pascale, A},
title = {Targeting the Gut-Eye Axis: An Emerging Strategy to Face Ocular Diseases.},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
pages = {},
pmid = {37686143},
issn = {1422-0067},
mesh = {Humans ; Eye ; Face ; *Glaucoma ; *Macular Degeneration ; *Diabetic Retinopathy ; },
abstract = {The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut-eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.},
}
@article {pmid37685987,
year = {2023},
author = {Gross, C and Guérin, LP and Socol, BG and Germain, L and Guérin, SL},
title = {The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
pages = {},
pmid = {37685987},
issn = {1422-0067},
support = {FDN-143213/CAPMC/CIHR/Canada ; },
mesh = {Animals ; Humans ; Male ; Cell Communication ; *Clusterin/genetics ; *Eye Diseases/genetics ; *Neoplasms/genetics ; Semen ; Sheep ; Wound Healing ; },
abstract = {Clusterin (CLU) is a glycoprotein originally discovered in 1983 in ram testis fluid. Rapidly observed in other tissues, it was initially given various names based on its function in different tissues. In 1992, it was finally named CLU by consensus. Nearly omnipresent in human tissues, CLU is strongly expressed at fluid-tissue interfaces, including in the eye and in particular the cornea. Recent research has identified different forms of CLU, with the most prominent being a 75-80 kDa heterodimeric protein that is secreted. Another truncated version of CLU (55 kDa) is localized to the nucleus and exerts pro-apoptotic activities. CLU has been reported to be involved in various physiological processes such as sperm maturation, lipid transportation, complement inhibition and chaperone activity. CLU was also reported to exert important functions in tissue remodeling, cell-cell adhesion, cell-substratum interaction, cytoprotection, apoptotic cell death, cell proliferation and migration. Hence, this protein is sparking interest in tissue wound healing. Moreover, CLU gene expression is finely regulated by cytokines, growth factors and stress-inducing agents, leading to abnormally elevated levels of CLU in many states of cellular disturbance, including cancer and neurodegenerative conditions. In the eye, CLU expression has been reported as being severely increased in several pathologies, such as age-related macular degeneration and Fuch's corneal dystrophy, while it is depleted in others, such as pathologic keratinization. Nevertheless, the precise role of CLU in the development of ocular pathologies has yet to be deciphered. The question of whether CLU expression is influenced by these disorders or contributes to them remains open. In this article, we review the actual knowledge about CLU at both the protein and gene expression level in wound healing, and explore the possibility that CLU is a key factor in cancer and eye diseases. Understanding the expression and regulation of CLU could lead to the development of novel therapeutics for promoting wound healing.},
}
@article {pmid37685886,
year = {2023},
author = {Rosa, JGS and Disner, GR and Pinto, FJ and Lima, C and Lopes-Ferreira, M},
title = {Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives.},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
pages = {},
pmid = {37685886},
issn = {1422-0067},
support = {2021/08891-8//S&#xe3;o Paulo Research Foundation/ ; 2013/07467-1//S&#xe3;o Paulo Research Foundation/ ; },
mesh = {Humans ; *Retinal Degeneration/therapy ; *Macular Degeneration/therapy ; *Retinitis Pigmentosa/genetics/therapy ; Biomarkers ; Blindness ; Retina ; },
abstract = {Visual impairment and blindness are a growing public health problem as they reduce the life quality of millions of people. The management and treatment of these diseases represent scientific and therapeutic challenges because different cellular and molecular actors involved in the pathophysiology are still being identified. Visual system components, particularly retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune responses activated by local insults contribute to biological events, culminating in vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and some of them, such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and diabetic retinopathy, are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cell degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiological and molecular features and biochemical hallmarks, and possible research directions for novel treatments to assist as a guide for innovative research. The knowledge expansion upon the mechanistic bases of the pathobiology of eye diseases, including information on complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors, will prompt the identification of new therapeutic strategies.},
}
@article {pmid37685562,
year = {2023},
author = {Nagata, J and Shiose, S and Ishikawa, K and Fukui, T and Kano, K and Mori, K and Nakama, T and Notomi, S and Sonoda, KH},
title = {Clinical Characteristics of Eyes with Neovascular Age-Related Macular Degeneration and Retinal Pigment Epithelium Tears.},
journal = {Journal of clinical medicine},
volume = {12},
number = {17},
pages = {},
pmid = {37685562},
issn = {2077-0383},
abstract = {BACKGROUND: Although anti-vascular endothelial growth factor (anti-VEGF) therapy is the first choice of treatment for eyes with neovascular age-related macular degeneration (AMD), it sometimes results in retinal pigment epithelium (RPE) tears. This study presents the detailed clinical characteristics of RPE tears to help predict their occurrence before anti-VEGF therapy initiation.<br><br>METHODS: This study retrospectively analyzed neovascular age-related macular degeneration (nAMD) patients who visited the Kyushu University Hospital and started anti-VEGF therapy between April 2013 and June 2020. Using medical records, we collected the clinical data of patients with RPE tears, including age, sex, best-corrected visual acuity (BCVA), number of anti-VEGF drug injections and the type and size of pigment epithelial detachment (PED).<br><br>RESULTS: RPE tears occurred in 16 (1.50%) eyes of 16 patients in all 1068 nAMD eyes of 987 patients. The mean age of these patients with RPE tear was 81.7 &#xb1; 8.7 years. Fifteen eyes had typical AMD and one eye had polypoidal choroidal vasculopathy. The mean number of anti-VEGF drug injections before RPE tears was 5.0 &#xb1; 5.1. All patients experienced PED before the RPE tear (hemorrhagic, 4 eyes; serous vascular, 2 eyes; fibrovascular, 10 eyes). The average PED height and area were 615.7 &#xb1; 175.3 &#x3bc;m and 21.0 &#xb1; 7.2 mm[2], respectively. The sub-RPE cleft was observed in 10 eyes. The logMAR BCVA immediately after the RPE tear (0.73 &#xb1; 0.40) at 6 months (0.86 &#xb1; 0.51) and 12 months (0.84 &#xb1; 0.43) after the RPE tear were significantly worse than that before the RPE tear (0.58 &#xb1; 0.31; p < 0.05). The BCVA of patients with RPE tears that spread to the fovea was poorer than that of patients without RPE tears.<br><br>CONCLUSIONS: In patients with nAMD, RPE tears tended to occur in typical AMD eyes with high or large PEDs, and sub-RPE clefts. The visual prognosis depended on whether the RPE tear included the fovea.},
}
@article {pmid37685384,
year = {2023},
author = {Wylęgała, A and Wozniak, P and Sędziak-Marcinek, B and Bolek, B and Szkodny, D and Wylęgała, E},
title = {Retro-Mode in NIDEK Mirante: A Comparative Analysis with Other Imaging Modalities for AMD and CSR.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {17},
pages = {},
pmid = {37685384},
issn = {2075-4418},
abstract = {BACKGROUND: Retro-mode is a novel technique capable of creating pseudo-3D images of the retina. However, its clinical utility remains unknown. This study aimed to evaluate the Nidek Mirante multimodal imaging platform for ocular assessment in patients with various retinal conditions.<br><br>METHODS: A total of 115 participants with central serous chorioretinopathy (CSR) and age-related macular degeneration (AMD) were included. Two experienced graders independently evaluated the images, and statistical analysis was performed to assess interclass correlation coefficients (ICC) between graders and modalities; Results: For CSR detection, retro-mode demonstrated exceptionally high ICC rates (ICC = 1; 100%), while color and autofluorescence (FAF) showed moderate coefficients (0.69 and 0.78, respectively). The detection of pigment epithelial detachment was high across all methods, with only retro-mode deviated right (DR) allowing detection in 69% of cases, while retro-mode DR and deviated left (DL) achieved 100% detection. FAF-green achieved a 95% detection rate. In detecting retinal atrophy, most modalities demonstrated high detection rates, with the lowest detection rates offered by retro-mode DL (ICC = 0.85) and DR (ICC = 0.89), while retro-mode ring aperture offered 0.97. Infra-red and fluorescein angiography imaging offered the highest detection rates among the tested modalities, with 97% and 100%, respectively.<br><br>CONCLUSION: Retro-mode showed promise for comprehensive ocular evaluation and diagnosis, with certain imaging modalities demonstrating higher accuracy in detecting specific retinal features.},
}
@article {pmid37685269,
year = {2023},
author = {Yang, Y and Sun, Z and Li, Z and Wang, Q and Yan, M and Li, W and Xu, K and Shen, T},
title = {Identification of the Immune Landscapes and Follicular Helper T Cell-Related Genes for the Diagnosis of Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {17},
pages = {},
pmid = {37685269},
issn = {2075-4418},
support = {2021-I2M-1-050//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences/ ; 81770228//National Natural Science Foundation of China/ ; 82073264//National Natural Science Foundation of China/ ; 81770858//National Natural Science Foundation of China/ ; 81600618//National Natural Science Foundation of China/ ; 82170890//National Natural Science Foundation of China/ ; 2018YFC2000100//National Key R&amp;D Program of China/ ; 21-2016004//National High Level Hospital Clinical Research Funding/ ; BJ-2021-199//National High Level Hospital Clinical Research Funding/ ; BJ-2019-159//National High Level Hospital Clinical Research Funding/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a progressive ocular ailment causing age-associated vision deterioration, characterized by dysregulated immune cell activity. Notably, follicular helper T (Tfh) cells have emerged as pivotal contributors to AMD pathogenesis. Nonetheless, investigations into Tfh-associated gene biomarkers for this disorder remain limited.<br><br>METHODS: Utilizing gene expression data pertinent to AMD procured from the Gene Expression Omnibus (GEO) repository, we employed the "DESeq2" R software package to standardize and preprocess expression levels. Concurrently, CIBERSORT analysis was utilized to compute the infiltration proportions of 22 distinct immune cell types. Subsequent to weighted gene correlation network analysis (WGCNA), coupled with differential expression scrutiny, we pinpointed genes intricately linked with Tfh cells. These potential genes underwent further screening using the MCODE function within Cytoscape software. Ultimately, a judicious selection of pivotal genes from these identified clusters was executed through the LASSO algorithm. Subsequently, a diagnostic nomogram was devised based on these selected genes.<br><br>RESULTS: Evident Tfh cell disparities between AMD and control cohorts were observed. Our amalgamated analysis, amalgamating differential expression data with co-expression patterns, unveiled six genes closely associated with Tfh cells in AMD. Subsequent employment of the LASSO algo-rithm facilitated identification of the most pertinent genes conducive to predictive modeling. From these, GABRB3, MFF, and PROX1 were elected as prospective diagnostic biomarkers for AMD.<br><br>CONCLUSIONS: This investigation discerned three novel biomarker genes, linked to inflammatory mechanisms and pivotal in diagnosing AMD. Further exploration of these genes holds potential to foster novel therapeutic modalities and augment comprehension of AMD's disease trajectory.},
}
@article {pmid37684667,
year = {2023},
author = {Fan, R and Su, L and Zhang, H and Jiang, Y and Yu, Z and Zhang, X and Li, X},
title = {Enhanced therapeutic effect of PEDF-loaded mesenchymal stem cell-derived small extracellular vesicles against oxygen-induced retinopathy through increased stability and penetrability of PEDF.},
journal = {Journal of nanobiotechnology},
volume = {21},
number = {1},
pages = {327},
pmid = {37684667},
issn = {1477-3155},
support = {2021YJSS148//Tianjin Research Innovation Project for Postgraduate Students/ ; 81800880//National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ ; 82171042//National Natural Science Foundation of China/ ; 81870675//National Natural Science Foundation of China/ ; 18ZXRHSY00210//Key Project of Internet Cross-Border Integration Innovation and Technology of Tianjin/ ; TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; },
mesh = {Animals ; Mice ; Oxygen ; *Retinal Diseases ; *Extracellular Vesicles ; Inflammation ; *Mesenchymal Stem Cells ; Neovascularization, Pathologic ; },
abstract = {BACKGROUND: Several common retinal diseases that cause blindness are characterised by pathological neovascularisation accompanied by inflammation and neurodegeneration, including retinopathy of prematurity (ROP), diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). The current treatment strategies for these diseases have limited benefits. Thus, safer and more effective alternative approaches are required. In this study, we loaded small extracellular vesicles (sEVs) derived from mesenchymal stem cell (MSC) with pigment epithelium-derived factor (PEDF), and tested the therapeutic effect of PEDF-loaded sEVs (PEDF-sEVs) using an oxygen induced retinopathy (OIR) mouse model, aiming to establish a new therapy strategy for the treatment of retinal pathological angiogenesis.<br><br>RESULTS: We formulated PEDF-loaded sEVs (PEDF-sEVs) containing high concentrations of PEDF and evaluated their effects through in vivo and in vitro experiments. In OIR mice, PEDF-sEVs showed significantly better effects on retinal avascular areas, inflammation, and neuronal degeneration compared with the anti-vascular endothelial growth factor (VEGF) drug, which may indicate a possible advantage of PEDF-sEVs over anti-VEGF drugs in the treatment of pathological neovascularisation. In vitro, PEDF-sEVs greatly inhibited endothelial cell (EC) proliferation, migration, and tube formation by suppressing the VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT (also known as Protein Kinase B). All experiments and analyses were performed in triplicate. PEDF-sEVs were more effective than PEDF or sEVs alone, both in vitro and in vivo. Furthermore, to determine the distribution of PEDF-sEVs, we used DiD-labelled sEVs and FITC-labelled PEDF to track the sEVs and PEDF, respectively. We found that PEDF-sEVs effectively reduced the degradation of PEDF.<br><br>CONCLUSIONS: Loading PEDF on sEVs effectively enhanced the anti-angiogenic, anti-inflammatory, and neuroprotective effects of PEDF by increasing the stability and penetrability. These results suggest a potential role for PEDF-sEVs in retinal pathological neovascularisation.},
}
@article {pmid37684383,
year = {2023},
author = {Janetos, TM and Zandi, R and Younessi, D and Johnson, G and Randolph, A and Gill, M},
title = {Clinical outcomes in neovascular age-related macular degeneration: a cohort study of patients with care delay due to the COVID-19 pandemic.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {14814},
pmid = {37684383},
issn = {2045-2322},
mesh = {Humans ; *COVID-19/epidemiology ; Cohort Studies ; Communicable Disease Control ; Pandemics ; *Macular Degeneration/epidemiology/therapy ; },
abstract = {The COVID-19 pandemic has led to both intentional and unintentional care delay among age-related neovascular macular degeneration (nvAMD) patients. Prior studies have demonstrated that patients who discontinue nvAMD treatment for prolonged intervals are at high risk for vision loss, but less is known regarding shorter-term delay, such as during the height of the pandemic. Previous studies have looked at COVID-19 related delay in care and have shown a loss of visual acuity (VA) among these patients, but studies are limited by short follow-up or insufficient comparisons. This was an observational cohort study of nvAMD patients from March 1, 2019, through July 1, 2021, who experienced care delay. VA was modeled using a linear longitudinal mixed-effects model comparing historic data pre-lockdown to data post-lockdown. Covariates included baseline anatomic variables, demographic variables, and time intervals (treatment interval, delay interval). Secondary anatomic and treatment outcomes were modeled using a multilevel binary logistic regression model. 163 eyes among 116 patients were included. Initial longitudinal mixed-effects models found that although overall VA decreased at a yearly rate, when comparing pre-lockdown and post-lockdown time periods, VA slopes were not statistically different. Single-covariate longitudinal models showed that age, sex, and delay interval significantly affected VA slope. The multivariate longitudinal model found that a longer delay interval significantly decreased rate of VA loss. Multilevel binary logistic regression models showed a significant increase in odds of anti-VEGF treatment, presence of subretinal fluid, and macular hemorrhages in the post-lockdown period. Overall, when compared to historic data, rate of VA loss among our cohort did not vary significantly in pre-versus post-lockdown time periods, although treatment and anatomic variables did worsen post-lockdown suggesting that patients may be appropriately delayed but this comes at the risk of increased need for treatment.},
}
@article {pmid37683842,
year = {2023},
author = {Korhonen, E and Piippo, N and Hytti, M and Kaarniranta, K and Kauppinen, A},
title = {Cis-urocanic acid improves cell viability and suppresses inflammasome activation in human retinal pigment epithelial cells.},
journal = {Biochemical pharmacology},
volume = {216},
number = {},
pages = {115790},
doi = {10.1016/j.bcp.2023.115790},
pmid = {37683842},
issn = {1873-2968},
abstract = {Age-related macular degeneration (AMD) is a common eye disease among the elderly, which can result in impaired vision and irreversible loss of vision. The majority of patients suffer from the dry (also known as the atrophic) form of the disease, which is completely lacking an effective treatment. In the present study, we evaluated the potential of cis-urocanic acid (cis-UCA) to protect human ARPE-19 cells from cell damage and inflammasome activation induced by UVB light. Urocanic acid is a molecule normally present in human epidermis. Its cis-form has recently been found to alleviate UVB-induced inflammasome activation in human corneal epithelial cells. Here, we observed that cis-UCA is well-tolerated also by human retinal pigment epithelial (RPE) cells at a concentration of 100 μg/ml. Moreover, cis-UCA was cytoprotective and efficiently diminished the levels of mature IL-1β, IL-18, and cleaved caspase-1 in UVB-irradiated ARPE-19 cells. Interestingly, cis-UCA also reduced DNA damage, whereas its effect against ROS production was negligible. Collectively, cis-UCA protected ARPE-19 cells from UVB-induced phototoxicity and inflammasome activation. This study indicates that due to its beneficial properties of preserving cell viability and preventing inflammation, cis-UCA has potential in drug development of chronic ocular diseases, such as AMD.},
}
@article {pmid37683194,
year = {2024},
author = {Nanegrungsunk, O and Corradetti, G and Phinyo, P and Choovuthayakorn, J and Sadda, SR},
title = {PREVALENCE AND PERSISTENCE OF HYPERTRANSMISSION DEFECTS OF VARIOUS SIZES IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {1},
pages = {20-27},
doi = {10.1097/IAE.0000000000003929},
pmid = {37683194},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; Prevalence ; *Macular Degeneration/diagnosis/epidemiology/pathology ; Tomography, Optical Coherence/methods ; Choroid/pathology ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To determine the prevalence and rate of persistence over 2 years of various-sized hypertransmission defects (hyperTDs) in eyes with intermediate age-related macular degeneration.<br><br>METHODS: Retrospective analysis of optical coherence tomography data from consecutive intermediate age-related macular degeneration patients. Choroidal en face optical coherence tomography images were evaluated for the presence and number of hyperTDs of three different sizes based on greatest linear dimension (small, 63-124 &#xb5; m; medium, 125-249 &#xb5; m; large, &#x2265;250 &#xb5; m) at baseline and at the 2-year follow-up. Interreader agreement was determined by Gwet's agreement coefficient. Disagreements between graders were resolved by the senior investigator to yield a single consensus for all cases.<br><br>RESULTS: From 273 intermediate age-related macular degeneration eyes (247 patients), 72 and 76 hyperTD lesions were independently identified by two graders at baseline and overall agreement coefficient was 0.89 (95% CI, 0.86-0.93). After adjudication by the senior grader, the final consensus yielded 78 hyperTD lesions from 46 eyes (16.8%) of 42 patients (17.0%) in this study cohort. Among eyes with follow-up optical coherence tomography, 32 of 45 hyperTD lesions (71.1%) persisted. The rates of persistence were 100.0%, 72.7%, and 53.3% in large, medium, and small hyperTD sizes, respectively.<br><br>CONCLUSION: HyperTDs were present in a significant proportion of intermediate age-related macular degeneration eyes. Acceptable interreader agreement was demonstrated in identifying hyperTD. Larger hyperTD lesions were more likely to persist over 2 years.},
}
@article {pmid37682568,
year = {2023},
author = {Moir, J and Hyman, M and Wang, J and Flores, A and Skondra, D},
title = {The Association of Antibiotic Use and the Odds of a New-Onset ICD Code Diagnosis of Age-Related Macular Degeneration: A Large National Case-Control Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {12},
pages = {14},
pmid = {37682568},
issn = {1552-5783},
mesh = {Humans ; *Anti-Bacterial Agents/adverse effects ; International Classification of Diseases ; Case-Control Studies ; Prospective Studies ; Aminoglycosides ; Fluoroquinolones ; *Macular Degeneration/diagnosis/epidemiology ; },
abstract = {PURPOSE: The widespread use of antibiotics has many well-documented impacts on the human microbiome, which may be associated with the development of various inflammatory diseases. Despite age-related macular degeneration (AMD) featuring an inflammatory pathogenesis, the relationship between antibiotics and AMD has remained unexplored. We conducted the first study to determine the association between antibiotic exposure and a new-onset International Classification of Diseases (ICD) diagnosis of AMD.<br><br>METHODS: We performed a case-control analysis of patients aged 55 and older with new-onset AMD between 2008 and 2017 from a nationwide commercial health insurance claims database. Exposure to antibiotics in the two years before the index date was determined for cases and controls matched one-to-one by age, year, region, anemia, hypertension, and a comorbidity index. Conditional multivariable logistic regression, adjusted for AMD risk factors, was performed to calculate odd ratios (OR) and 95% confidence intervals (CI).<br><br>RESULTS: Among the antibiotic classes, exposure to aminoglycosides (OR = 1.24; 95% CI, 1.22-1.26) and fluoroquinolones (OR = 1.13; 95% CI, 1.12-1.14) was associated with the greatest odds of a new-onset ICD code diagnosis of AMD. Broad-spectrum antibiotics were associated with nearly three times greater odds of a new-onset ICD code diagnosis of AMD (OR = 1.15; 95% CI, 1.13-1.16) compared to narrow-spectrum antibiotics (OR = 1.05; 95% CI, 1.03-1.07). We also identified a frequency- and duration-dependent association, with a greater cumulative number of antibiotic prescriptions or day supply of antibiotics conferring increased odds of a new-onset ICD code diagnosis of AMD.<br><br>CONCLUSIONS: Greater cumulative exposure to antibiotics, particularly fluoroquinolones, aminoglycosides, and those with broader-spectrum coverage, may be associated with the development of AMD, a finding that requires further investigation using prospective studies.},
}
@article {pmid37682567,
year = {2023},
author = {Shen, G and Li, Y and Zeng, Y and Hong, F and Zhang, J and Wang, Y and Zhang, C and Xiang, W and Wang, J and Fang, Z and Qi, W and Yang, X and Gao, G and Zhou, T},
title = {Kallistatin Deficiency Induces the Oxidative Stress-Related Epithelial-Mesenchymal Transition of Retinal Pigment Epithelial Cells: A Novel Protagonist in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {12},
pages = {15},
pmid = {37682567},
issn = {1552-5783},
mesh = {Animals ; Mice ; Rats ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; *Geographic Atrophy ; *Macular Degeneration/genetics ; Mice, Transgenic ; Oxidative Stress ; Reactive Oxygen Species ; Retinal Pigments ; *Serpins/genetics ; },
abstract = {PURPOSE: Retinal pigment epithelium (RPE) dysfunction induced by oxidative stress-related epithelial-mesenchymal transition (EMT) of RPE is the primary underlying mechanism of age-related macular degeneration (AMD). Kallistatin (KAL) is a secreted protein with an antioxidative stress effect. However, the relationship between KAL and EMT in RPE has not been determined. Therefore we aimed to explore the impact and mechanism of KAL in oxidative stress-induced EMT of RPE.<br><br>METHODS: Sodium iodate (SI) was injected intraperitoneally to construct the AMD rat model and investigate the changes in RPE morphology and KAL expression. KAL knockout rats and KAL transgenic mice were used to explain the effects of KAL on EMT and oxidative stress. In addition, Snail overexpressed adenovirus and si-RNA transfected ARPE19 cells to verify the involvement of Snail in mediating KAL-suppressed EMT of RPE.<br><br>RESULTS: AMD rats induced by SI expressed less KAL in the retina, and KAL knockout rats showed RPE dysfunction spontaneously where EMT and reactive oxygen species (ROS) production increased in RPE. In contrast, KAL overexpression attenuated EMT and ROS levels in RPE, even in TGF-&#x3b2; treatment. Mechanistically, Snail reversed the beneficial effect of KAL on EMT and ROS reduction. Moreover, KAL ameliorated SI-induced AMD-like pathological changes.<br><br>CONCLUSIONS: Our findings demonstrated that KAL inhibits oxidative stress-induced EMT by downregulating the transcription factor Snail. Herein, KAL knockout rats may be an appropriate animal model for observing spontaneous RPE dysfunction for AMD-like retinopathy, and KAL may represent a novel therapeutic target for treating dry AMD.},
}
@article {pmid37682553,
year = {2023},
author = {Dickson, SR and James, KE},
title = {Medicare Part B Spending on Macular Degeneration Treatments Associated With Manufacturer Payments to Ophthalmologists.},
journal = {JAMA health forum},
volume = {4},
number = {9},
pages = {e232951},
pmid = {37682553},
issn = {2689-0186},
mesh = {United States ; Male ; Humans ; Aged ; *Medicare Part B ; Bevacizumab/therapeutic use ; Cross-Sectional Studies ; *Ophthalmologists ; Retrospective Studies ; *Macular Degeneration/drug therapy ; },
abstract = {IMPORTANCE: Age-related macular degeneration (ARMD) therapies aflibercept and ranibizumab are among the highest-cost Medicare Part B drugs, even though off-label use of lower-cost bevacizumab is clinically noninferior. Payments from manufacturers of these ARMD therapies to ophthalmologists are hypothesized to be factors in ophthalmologists' therapeutic choice, controlling for ophthalmologist and patient characteristics.<br><br>OBJECTIVE: To assess the association between manufacturer payments to ophthalmologists and choice of ARMD treatment as well as to identify ophthalmologist-level characteristics associated with prescribing lower-cost ARMD therapies.<br><br>This retrospective cross-sectional study of longitudinal (2013-2019) Medicare Part B data was conducted from December 2021 to December 2022. Ophthalmologists prescribing aflibercept (manufactured by Regeneron Pharmaceuticals Inc), rabinizumab, or bevacizumab (both manufactured by Genentech Inc) for ARMD treatment of Medicare Part B beneficiaries were included. Data on manufacturer payments to ophthalmologists were obtained from the Open Payments database.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of bevacizumab prescribed by ophthalmologists among all ARMD therapies. Regression analysis assessed variation in bevacizumab prescribing by acceptance of manufacturer payments as well as by ophthalmologist and patient characteristics. Ophthalmologist characteristics were duration of practice and Medicare Administrative Contractor region, and patient characteristics were aggregated at the ophthalmologist level and included mean beneficiary age, percentage of dual-eligible beneficiaries, mean beneficiary risk score, and percentage of White beneficiaries. Savings were estimated by projecting the change in bevacizumab use had ophthalmologists not accepted manufacturer payments, controlling for all ophthalmologist and patient characteristics and comparing with observed use and costs.<br><br>RESULTS: A total of 21&#x202f;584 ophthalmologists (18 489 males [85.7%]) were included. Ophthalmologists who accepted manufacturer payments were significantly less likely to prescribe bevacizumab (28.0% [95% CI, 24.6%-42.5%] of patients) compared with those who did not accept manufacturer payments (45.8% [95% CI, 44.5%-47.1%]). Ophthalmologists who saw dual-eligible beneficiaries had greater bevacizumab prescribing (50.0% [95% CI, 40.6%-68.3%] in the highest quartile vs 36.1% [95% CI, 33.5%-38.8%] in the lowest quartile; &#x3b2; coefficient, 0.139; P&#x2009;<&#x2009;.001), while those who saw patients with higher mean beneficiary risk scores had lower bevacizumab use (38.0% [95% CI, 23.7%-44.1%] in the highest quartile vs 48.2% [95% CI, 45.5%-50.8%] in the lowest quartile; &#x3b2; coefficient, -0.102, P&#x2009;<&#x2009;.001). Had ophthalmologists who accepted manufacturer payments prescribed ARMD drugs as those who did not accept payments, Medicare spending on these treatments would have been $642&#x202f;779&#x202f;703.08 lower from 2013 to 2019, a 2.0% savings.<br><br>CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that drug manufacturer payments to ophthalmologists were associated with selection of higher-cost therapies for ARMD, which is a factor in increased Medicare and patient spending. Development of manufacturer payment models that encourage ophthalmologists to choose lower-cost therapies are needed.},
}
@article {pmid37680284,
year = {2023},
author = {Yilmaz, M and Citirik, M and Rahmanlar, H and Alkan, A and Gursoz, H},
title = {Off-Label Uses of Ranibizumab and Aflibercept for Age-Related Macular Degeneration in Turkey.},
journal = {Journal of current ophthalmology},
volume = {35},
number = {1},
pages = {61-65},
pmid = {37680284},
issn = {2452-2325},
abstract = {PURPOSE: To evaluate the clinical and demographic aspects of off-label drug use applications for age-related macular degeneration (AMD) in Turkey.<br><br>METHODS: Applications for off-label drug use in the treatment of AMD to the Turkish Medicines and Medical Devices Agency (TITCK) in 2018 were retrospectively analyzed. Demographic characteristics, requested drugs, previous treatment regimens, and reasons for applications were evaluated.<br><br>RESULTS: The mean age of the patients (n = 209) was 64.9 &#xb1; 15.7 years, of which 48.8% were male and 51.2% were female. Ranibizumab (n = 113) comprised 54.1% and aflibercept (n = 96) 45.9% of off-label use applications. No application was made for bevacizumab. The most frequent reasons for application were switchback (49.3%), nonreimbursement of indicated drugs in cases under 50 years of age (24.4%), and failure to complete the loading dose (14.4%).<br><br>CONCLUSIONS: Ranibizumab was the most requested off-label drug for AMD. There was no application for off-label bevacizumab since its use does not require approval from TITCK. In Turkey, new rules were established for the reimbursement of intravitreal drugs for AMD in 2019. Three doses of intravitreal bevacizumab were required initially for aflibercept and ranibizumab to be covered for reimbursement. There is not enough data in the English literature regarding the off-label use of ranibizumab and aflibercept for AMD. This study provides information about drug regulations and the off-label treatment options preferred by physicians for AMD in Turkey.},
}
@article {pmid37680141,
year = {2023},
author = {Vangsted, A and Thinggaard, BS and Nissen, AHK and Hajari, JN and Klefter, ON and Krogh Nielsen, M and Sørensen, TL and Grauslund, J and Subhi, Y},
title = {Prevalence of geographic atrophy in Nordic countries and number of patients potentially eligible for intravitreal complement inhibitor treatment: A systematic review with meta-analyses and forecasting study.},
journal = {Acta ophthalmologica},
volume = {101},
number = {8},
pages = {857-868},
doi = {10.1111/aos.15768},
pmid = {37680141},
issn = {1755-3768},
mesh = {Humans ; *Geographic Atrophy ; Prevalence ; Complement Inactivating Agents/therapeutic use ; Scandinavian and Nordic Countries ; Iceland ; },
abstract = {We systematically reviewed the literature on the prevalence of geographic atrophy (GA) in Nordic populations, conducted meta-analyses on age-stratified estimates, and calculated current and future number of patients and those potentially eligible for intravitreal complement inhibitor treatment. We followed the PRISMA guidelines, and our protocol was registered in PROSPERO. Ten databases were searched on 22 April 2023 for population-based studies of GA prevalence. Based on clinical descriptive analyses of GA and eligibility criteria of the phase III studies for intravitreal pegcetacoplan (complement C3 and C3b inhibitor), we were able to calculate the proportion of patients with GA potentially eligible for therapy. Finally, we extracted population data for Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from Eurostat, applied prevalence statistics to the extracted census and forecasting data to estimate the number of patients with GA, and then applied the proportion eligible for intravitreal pegcetacoplan therapy. We identified six studies with a total of 10 159 individuals. Prevalence of GA was estimated to 0.4% (95% confidence intervals [CI]: 0.2%-0.8%), 1.5% (95% CI: 0.7%-2.6%), and 7.6% (95% CI: 4.6%-11.3%) for individuals aged 60-69, 70-79, and 80+ years, respectively. In Nordic countries, we estimate a total of 166 307 individuals with GA in 2023, increasing to 277 893 in 2050. Of these, 90 803 individuals in 2023, increasing to 151 730 in 2050, are potentially eligible for intravitreal complement inhibitor treatment. Considering these large numbers, our study highlights the importance of this topic in the coming years and its potential to significantly impact our clinical practice, organization, and staffing.},
}
@article {pmid37679852,
year = {2023},
author = {Venkatesh, R and Handa, A and Prabhu, V and Chitturi, SP and Joshi, A and Acharya, I and Mangla, R and Yadav, NK and Chhablani, J},
title = {Central posterior hyaloid fibrosis: evolution and outcomes.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {54},
pmid = {37679852},
issn = {2056-9920},
abstract = {PURPOSE: To report contributory factors and clinical outcomes of central posterior hyaloid fibrosis (CPHF) associated with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: In this retrospective, single-center study, patients with CPHF and nAMD were included. Demographic and imaging characteristics, as well as the anatomical and functional outcomes, of these patients were analysed.<br><br>RESULTS: We identified 530 eyes in 273 patients with chronic predominantly scarred macular neovascularisation (MNV), and 32 eyes in 29 patients revealed CPHF, representing a prevalence of 6%. Patients had a mean age of 72.76 years. Before and during the development of CPHF, Type 2 MNV was observed in all eyes. At the time of MNV diagnosis, mean logMAR visual acuity was 1.308&#x2009;&#xb1;&#x2009;0.559 (20/407). The average time to develop CPHF was 27.3 months since the diagnosis of MNV. At the time of CPHF identification, the mean logMAR visual acuity was 1.498&#x2009;&#xb1;&#x2009;0.374 (20/630). RPE tear was observed in 6% (n&#x2009;=&#x2009;2) of CPHF eyes. The average number of intravitreal anti-VEGF injections administered prior to the diagnosis of CPHF was 2.4 and after the onset of CPHF was 0.9. The final visual acuity was not significantly different at the final follow-up visit [1.304&#x2009;&#xb1;&#x2009;0.42 (20/402); p&#x2009;=&#x2009;0.646].<br><br>CONCLUSION: Rarely observed in eyes with predominantly scarred subfoveal type 2 MNVs and extensive subretinal fibrosis, CPHF is associated with poor visual outcomes. Its presence could possibly suggest a profibrotic effect of MNV on the posterior hyaloid.<br><br>TRIAL REGISTRATION NUMBER: Not applicable.},
}
@article {pmid37678979,
year = {2023},
author = {Han, G and Wei, P and Han, Q},
title = {Application of IPSC and Müller glia derivatives in retinal degenerative diseases.},
journal = {Progress in molecular biology and translational science},
volume = {199},
number = {},
pages = {351-362},
doi = {10.1016/bs.pmbts.2023.03.026},
pmid = {37678979},
issn = {1878-0814},
mesh = {Humans ; *Induced Pluripotent Stem Cells ; Neuroglia ; *Retinitis Pigmentosa ; Eye ; *Optic Nerve Diseases ; },
abstract = {Retinal degenerative diseases cause blindness characterized by a progressive decline in the number and function of retinal pigment epithelium (RPE), photoreceptor cells, and ganglion cells. Such diseases include retinitis pigmentosa (RP), glaucomatous optic neuropathy, age-related macular degeneration and diabetic optic neuropathy. Recent studies have demonstrated that Müller glial cells (MGCs), an endogenous alternative source of retinal neurons, are important glial cells involved in retinal development, damage, and regeneration, making it an excellent target for retinal nerve regeneration. Although hardly differentiate into neuron cells, transplanted MGCs have been shown to induce partial recovery of visual function in experimental retinal degenerative models. This improvement is possibly attributed to the release of neuroprotective factors that derived from the MGCs. With the development of the therapeutic usage of pluripotent stem cell, application of induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) originated derivation of MGCs have been widely used in retinal degenerative disease model such as glaucoma and retinitis pigmentosa model. This chapter summarized the relevant research and mechanisms and provided a broader application and research prospects for effective treatments in retinal degenerative diseases.},
}
@article {pmid37678973,
year = {2023},
author = {Liu, Q and Liu, J and Higuchi, A},
title = {hPSC-derived RPE transplantation for the treatment of macular degeneration.},
journal = {Progress in molecular biology and translational science},
volume = {199},
number = {},
pages = {227-269},
doi = {10.1016/bs.pmbts.2023.02.010},
pmid = {37678973},
issn = {1878-0814},
mesh = {Aged ; Humans ; *Macular Degeneration/therapy ; Cell Differentiation ; *Pluripotent Stem Cells ; },
abstract = {Macular degeneration (MD) is a group of diseases characterized by irreversible and progressive vision loss. Patients with MD suffer from severely impaired central vision, especially elderly people. Currently, only one type of MD, wet age-related macular degeneration (AMD), can be treated with anti-vascular endothelium growth factor (VEGF) drugs. Other types of MD remain difficult to treat. With the advent of human pluripotent stem cells (hPSCs) and their differentiation into retinal pigmented epithelium (RPE), it is promising to treat patients with MD by transplantation of hPSC-derived RPE into the subretinal space. In this review, the current progress in hPSC-derived RPE transplantation for the treatment of patients with MD is described from bench to bedside, including hPSC differentiation into RPE and the characterization and usage of hPSC-derived RPE for transplantation into patients with MD.},
}
@article {pmid37677008,
year = {2023},
author = {Attarde, A and Riad, TS and Zhang, Z and Ahir, M and Fu, Y},
title = {Characterization of Vascular Morphology of Neovascular Age-Related Macular Degeneration by Indocyanine Green Angiography.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {198},
pages = {},
pmid = {37677008},
issn = {1940-087X},
support = {P30 EY002520/EY/NEI NIH HHS/United States ; R01 EY033805/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Indocyanine Green ; Fluorescein Angiography ; *Macular Degeneration/diagnostic imaging ; Blindness ; *Choroidal Neovascularization/diagnostic imaging ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among older individuals, and its prevalence is rapidly increasing due to the aging population. Choroidal neovascularization (CNV) or wet AMD, which accounts for 10%-20% of all AMD cases, is responsible for an alarming 80%-90% of AMD-related blindness. Current anti-VEGF therapies show suboptimal responses in approximately 50% of patients. Resistance to anti-VEGF treatment in CNV patients is often associated with arteriolar CNV, while responders tend to have capillary CNV. While fluorescein angiography (FA) is commonly used to assess leakage patterns in wet AMD patients and animal models, it does not provide information about CNV vascular morphology (arteriolar CNV vs. capillary CNV). This protocol introduces the use of indocyanine green angiography (ICGA) to characterize lesion types in laser-induced CNV mouse models. This method is crucial for investigating the mechanisms and treatment strategies for anti-VEGF resistance in wet AMD. It is recommended to incorporate ICGA alongside FA for comprehensive assessment of both leakage and vascular features of CNV in mechanistic and therapeutic studies.},
}
@article {pmid37676679,
year = {2023},
author = {Trinh, M and Kalloniatis, M and Alonso-Caneiro, D and Nivison-Smith, L},
title = {Spatial Cluster Patterns of Retinal Sensitivity Loss in Intermediate Age-Related Macular Degeneration Features.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {9},
pages = {6},
pmid = {37676679},
issn = {2164-2591},
mesh = {Humans ; Retina ; *Macular Degeneration/epidemiology ; *Retinal Drusen ; *Macula Lutea ; Transcription Factors ; },
abstract = {PURPOSE: To examine spatial patterns of retinal sensitivity loss in the three key features of intermediate age-related macular degeneration (iAMD).<br><br>METHODS: One-hundred individuals (53 iAMD, 47 normal) underwent 10-2 mesopic microperimetry testing in one eye. Pointwise sensitivities (dB) were corrected for age, sex, iAMD status, and co-presence of co-localized key iAMD features: drusen load, pigmentary abnormalities, and reticular pseudodrusen (RPD). Clusters (labeled by ranks of magnitude C-2, C-1, C0) were derived from pointwise sensitivities and then assessed by quadrants and eccentricity/rings.<br><br>RESULTS: Two clusters of decreased sensitivities were evident in iAMD versus normal: C-2, -1.67 dB (95% CI (confidence intervals), -2.36 to -0.98; P < 0.0001); C-1, -0.93 dB (95% CI, -1.5 to -0.36; P < 0.01). One cluster of decreased sensitivity was independently associated each with increased drusen load (13.57 &#xb5;m increase per -1 dB; P < 0.0001), pigmentary abnormalities (C-1: -2.23 dB; 95% CI, -3.36 to -1.1; P < 0.01), and RPD (C-1: -1.07 dB; 95% CI, -2 to -0.14; P < 0.01). Sensitivity loss in iAMD was biased toward the superior and central macula (P = 0.16 to <0.0001), aligning with structural distributions of features. However, sensitivity loss associated with drusen load also extended to the peripheral macula (P < 0.0001) with paracentral sparing, which was discordant with the central distribution of drusen.<br><br>CONCLUSIONS: Drusen load, pigmentary abnormalities, and RPD are associated with patterns of retinal sensitivity loss commonly demonstrating superior and central bias. Results highlighted that a clinical focus on these three key iAMD features using structural measures alone does not capture the complex, spatial extent of vision-related functional impairment in iAMD.<br><br>TRANSLATIONAL RELEVANCE: Defining the spatial patterns of retinal sensitivity loss in iAMD can facilitate a targeted visual field protocol for iAMD assessment.},
}
@article {pmid37676678,
year = {2023},
author = {Kwon, M and Owsley, C},
title = {Reading Vision in Adults With Early and Intermediate Age-Related Macular Degeneration Under Mesopic and Photopic Conditions.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {9},
pages = {7},
pmid = {37676678},
issn = {2164-2591},
support = {P30 AG022838/AG/NIA NIH HHS/United States ; R01 EY027857/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration ; *Reading ; Retinal Cone Photoreceptor Cells ; Adult ; },
abstract = {PURPOSE: Reading is involved in various daily activities that operate under a wide range of luminance levels. Rod- and cone-mediated mesopic visual function is known to be impaired even in early/intermediate age-related macular degeneration (AMD). It remains unclear whether and to what extent mesopic reading is impaired in early/intermediate AMD. Here, we assessed differences in reading vision between photopic and mesopic conditions in early/intermediate AMD and compared their performance to those in older adults with normal macular health.<br><br>METHODS: The study included 30 patients with early/intermediate AMD and 30 healthy controls. Reading performance was tested on the MNREAD iPad app under mesopic (2&#xa0;cd/m2 with a neural-density filter) and photopic (220 cd/m2) conditions. Four reading indices-maximum reading speed (MRS), critical print size (CPS), reading acuity (RA), and reading accessibility index (ACC)-were obtained from the MNREAD test, yielding a function representing reading speed versus print size.<br><br>RESULTS: Compared to photopic conditions, patients with AMD and healthy controls both exhibited noticeable decreases in reading vision under mesopic conditions (P < 0.001) despite normal photopic visual acuity. This decrease was more pronounced in AMD even after adjusting for age (P < 0.001): Under mesopic conditions, MRS and ACC decreased by 8 words per minute and 0.1, respectively; CPS and RA were enlarged by 0.27 and 0.24 logMAR, respectively.<br><br>CONCLUSIONS: Reading vision deteriorates under mesopic conditions compared to photopic conditions in early/intermediate AMD and is accentuated compared to this difference in healthy controls.<br><br>TRANSLATIONAL RELEVANCE: A mesopic reading test may provide a more sensitive and comprehensive assessment of a patient's reading impairment.},
}
@article {pmid37676536,
year = {2023},
author = {Tsao, YC and Chen, TY and Wang, LA and Lee, CC and Lee, WA and Hsu, SM and Lai, CC and Shao, SC and Hung, JH and Lai, EC},
title = {Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.},
journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy},
volume = {37},
number = {6},
pages = {843-854},
pmid = {37676536},
issn = {1179-190X},
support = {MOST 110-2314-B-006-086-MY3//Taiwan's Ministry of Science and Technology/ ; NCKUH-11006018//National Cheng Kung University Hospital/ ; },
mesh = {Humans ; *Acute Kidney Injury/chemically induced/complications/drug therapy ; Angiogenesis Inhibitors/adverse effects ; Bevacizumab/adverse effects ; *Diabetic Retinopathy/drug therapy/chemically induced/complications ; Endothelial Growth Factors/therapeutic use ; Intravitreal Injections ; *Macular Degeneration/chemically induced/complications/drug therapy ; *Macular Edema/drug therapy/chemically induced/complications ; Randomized Controlled Trials as Topic ; Ranibizumab/adverse effects ; Recombinant Fusion Proteins/adverse effects ; *Retinal Diseases/chemically induced/complications/drug therapy ; *Retinal Vein Occlusion/drug therapy/chemically induced/complications ; Systematic Reviews as Topic ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors/antagonists &amp; inhibitors ; },
abstract = {BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant.<br><br>OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases.<br><br>METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by&#xa0;a fixed-effects model for pooling odds ratios (ORs) using the Peto method.<br><br>RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I[2]: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I[2]: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I[2]: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I[2]: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I[2]: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I[2]: 0% for retinal vein occlusion).<br><br>CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved.<br><br>PROSPERO CRD42021267854.},
}
@article {pmid37674785,
year = {2023},
author = {Lei, S and Liu, Z and Li, H},
title = {Sleep duration and age-related macular degeneration: a cross-sectional and Mendelian randomization study.},
journal = {Frontiers in aging neuroscience},
volume = {15},
number = {},
pages = {1247413},
pmid = {37674785},
issn = {1663-4365},
abstract = {PURPOSE: To investigate the association between sleep duration and age-related macular degeneration (AMD).<br><br>DESIGN: Cross-sectional study, bidirectional two-sample Mendelian randomization (MR). For cross-sectional analysis, we used survey data of 5,481 participants aged &#x2265;40 years from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES). For MR analysis, we used sleep- and AMD-associated genome-wide association studies (GWAS) data involving large populations.<br><br>METHODS: The association between sleep duration and AMD was assessed using logistic regression models. For MR analysis, the primary approach for MR analysis was the inverse-variance weighted (IVW) method.<br><br>RESULTS: In cross-sectional analysis, after adjusting for multiple covariates, short sleep duration (SSD) was found to be associated with increased risk of early AMD [odds ratio (OR) = 1.364, P = 0.036). MR analysis supported the results of cross-sectional analysis: SSD increases the risk of early AMD (&#x3b2; = 0.102, IVW-P = 0.003).<br><br>CONCLUSION: Our findings provide the evidence supporting the association between sleep deficiency and higher risk of AMD. Further studies are required to confirm our findings and elucidate the mechanisms underlying this association.},
}
@article {pmid37673970,
year = {2024},
author = {Taylor, TRP and Menten, MJ and Rueckert, D and Sivaprasad, S and Lotery, AJ},
title = {The role of the retinal vasculature in age-related macular degeneration: a spotlight on OCTA.},
journal = {Eye (London, England)},
volume = {38},
number = {3},
pages = {442-449},
pmid = {37673970},
issn = {1476-5454},
mesh = {Humans ; Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Retinal Vessels/diagnostic imaging ; *Macular Degeneration ; Retina ; Choroid/blood supply ; },
abstract = {Age-related macular degeneration (AMD) remains a disease with high morbidity and an incompletely understood pathophysiological mechanism. The ocular blood supply has been implicated in the development of the disease process, of which most research has focused on the role of the choroid and choriocapillaris. Recently, interest has developed into the role of the retinal vasculature in AMD, particularly with the advent of optical coherence tomography angiography (OCTA), which enables non-invasive imaging of the eye's blood vessels. This review summarises the up-to-date body of work in this field including the proposed links between observed changes in the retinal vessels and the development of AMD and potential future directions for research in this area. The review highlights that the strongest evidence supports the observation that patients with early to intermediate AMD have reduced vessel density in the superficial vascular complex of the retina, but also emphasises the need for caution when interpreting such studies due to their variable methodologies and nomenclature.},
}
@article {pmid37673396,
year = {2024},
author = {Szigiato, A and Mohan, N and Talcott, KE and Mammo, DA and Babiuch, AS and Kaiser, PK and Ehlers, JP and Rachitskaya, A and Yuan, A and Srivastava, SK and Sharma, S},
title = {Short-Term Outcomes of Faricimab in Patients with Neovascular Age-Related Macular Degeneration on Prior Anti-VEGF Therapy.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {1},
pages = {10-17},
doi = {10.1016/j.oret.2023.08.018},
pmid = {37673396},
issn = {2468-6530},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Angiogenesis Inhibitors ; Cohort Studies ; Retrospective Studies ; Treatment Outcome ; *Retinal Detachment/drug therapy ; *Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: A subset of patients with neovascular age-related macular degeneration (nAMD) experience treatment burden and suboptimal response with anti-VEGF therapy. The aim of this study was to investigate the effect of switching to a novel, bispecific agent, faricimab, in patients with nAMD currently treated with anti-VEGF.<br><br>DESIGN: Retrospective, noncomparative cohort study.<br><br>SUBJECTS: Patients with nAMD previously treated with anti-VEGF and switched to intravitreal faricimab injection (IFI) at the Cleveland Clinic's Cole Eye Institute.<br><br>METHODS: Switching and administration schedule of IFI was at the discretion of the clinician. Visual acuity (VA) and macular OCT parameters, including central subfield thickness (CST), maximum pigment epithelial detachment (PED) height, and presence of subretinal (SRF) or intraretinal fluid (IRF), were assessed at baseline (day of first IFI) and after each IFI.<br><br>MAIN OUTCOME MEASURES: Central subfield thickness and presence of IRF or SRF after &#x2265; 3 IFIs.<br><br>RESULTS: One hundred twenty-six eyes of 106 patients were included in the analysis with a mean follow-up time of 24.3 &#xb1; 5.2 weeks. Before switching to IFI, patients received a mean of either aflibercept (20.0 &#xb1; 8.4, mean &#xb1; standard deviation), bevacizumab (7 &#xb1; 8.9), ranibizumab (1.9 &#xb1; 8.5), or brolucizumab (0.3 &#xb1; 1.6) injections. The most common agent used before switching to IFI was aflibercept (n&#xa0;= 110, 87%), and the mean treatment interval with any anti-VEGF was 5.6 &#xb1; 1.6 weeks before switching. Central subfield thickness was reduced from baseline after the first IFI (266.8 &#xb1; 64.7 vs. 249.8 &#xb1; 58.6 &#x3bc;m, P&#xa0;= 0.02) and persisted over the 3 IFIs (P&#xa0;= 0.01). Pigment epithelial detachment height was reduced after the third IFI (249.6 &#xb1; 179.0 vs. 206.9 &#xb1; 130.0 &#x3bc;m, P&#xa0;= 0.01). The mean VA (62.9 vs. 62.7 approximate ETDRS letters, P&#xa0;=&#xa0;0.42) and interval between injections (6.3 vs. 5.7 weeks, P&#xa0;= 0.16) was similar after the third IFI compared with&#xa0;baseline. Eleven (8.7%) eyes were switched back to their previous anti-VEGF, including 2 (1.6%) eyes from&#xa0;1&#xa0;patient with intraocular inflammation requiring cessation of IFI. There were no other adverse events&#xa0;from&#xa0;switching.<br><br>CONCLUSIONS: Switching to faricimab resulted in a reduction in mean CST (-11.6 &#x3bc;m, P&#xa0;= 0.01) and PED height (-44.2 &#x3bc;m, P&#xa0;= 0.01) after 3 injections, with stable VA and at a similar treatment interval to prior anti-VEGF therapy.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37673374,
year = {2024},
author = {Jonas, JB and Jonas, RA and Xu, J and Wang, YX},
title = {Prevalence and Cause of Loss of Visual Acuity and Visual Field in Highly Myopic Eyes: The Beijing Eye Study.},
journal = {Ophthalmology},
volume = {131},
number = {1},
pages = {58-65},
doi = {10.1016/j.ophtha.2023.08.026},
pmid = {37673374},
issn = {1549-4713},
mesh = {Humans ; Middle Aged ; Aged ; Beijing ; Prevalence ; Visual Fields ; Risk Factors ; Visual Acuity ; *Myopia, Degenerative/complications ; *Optic Nerve Diseases/etiology ; Blindness/etiology ; Vision Disorders/etiology/complications ; *Macular Degeneration/epidemiology ; *Optic Atrophy ; },
abstract = {PURPOSE: To explore the prevalence and causes of loss of visual acuity and visual field in highly myopic eyes.<br><br>DESIGN: Population-based study.<br><br>PARTICIPANTS: 4439 subjects of the Beijing Eye Study underwent ophthalmological and systemic examinations including frequency doubling technology perimetry.<br><br>METHODS: High myopia was defined by a refractive error of &#x2264;-6 diopters (D) or axial length >26.0 mm.<br><br>MAIN OUTCOME MEASURES: Prevalence of vision impairment causes.<br><br>RESULTS: 212 highly myopic eyes from 154 participants were included with a mean age of 56.2 &#xb1; 9.6 years, a mean refractive error of -9.87 &#xb1; 3.70 D and a mean axial length of 27.2 &#xb1; 1.3 mm. We observed moderate/severe vision impairment (MSVI) in 40 eyes (18.9%; 95% confidence interval [CI], 13.6-24.2) and blindness in 10 eyes (4.7%; 95% CI, 1.8-7.6). Primary causes for MSVI and blindness were myopic macular degeneration (MMD) (29/50; 58%), age-related macular degeneration (1/50; 2%), and branch macular retinal vein occlusion (1/50; 2%). Secondary causes were MMD (4/50; 8%) and optic nerve atrophy (14/50, 28%), further differentiated into non-glaucomatous optic atrophy (NGOA) (9/50; 18%) and glaucomatous optic atrophy (GOA) (5/50; 10%). Prevalence of MMD as vision impairment cause increased significantly from 1/61 (1.6%) in the refractive error group of -6.00 to &#x2265;-7.00 D, to 16/25 (64%) in the group of <-15.0 D. Higher MMD prevalence correlated with higher myopic refractive error (P < 0.001) and increased likelihood of concomitant optic neuropathy (P < 0.001). Similarly, prevalence of optic neuropathy as vision impairment cause increased from 0/61 (0%) in the refractive error group of -6.00 D to &#x2265;-7.00 D, to 9/25 (36%) in the group of <-15.0 D. Higher optic neuropathy prevalence correlated with more myopic refraction (P < 0.001) and older age (P&#xa0;= 0.02).<br><br>CONCLUSIONS: In this population-based recruited cohort of highly myopic patients, optic neuropathy accounted for vision impairment in 9.0% eyes, which was lower than the prevalence of MMD as vision impairment cause (18.9%). Notably, optic neuropathy became a significant contributor to vision impairment in more advanced high myopia, reaching 36% in the group with refractive error of <-15.0 D.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37673087,
year = {2024},
author = {Abdin, AD and Eppinger, A and Aljundi, W and Abu-Dail, Y and Munteanu, C and Weinstein, I and Seitz, B},
title = {Vision-Related Quality of Life among Patients with Different Types of Age-Related Macular Degeneration.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {241},
number = {3},
pages = {283-291},
doi = {10.1055/a-2134-7622},
pmid = {37673087},
issn = {1439-3999},
mesh = {Humans ; Male ; Aged ; Aged, 80 and over ; Female ; Quality of Life/psychology ; Sickness Impact Profile ; Prospective Studies ; Visual Acuity ; Surveys and Questionnaires ; *Macular Degeneration/diagnosis/complications ; *Retinal Diseases ; },
abstract = {BACKGROUND: This study aimed to assess the vision-related quality of life (VRQol) of patients with age-related macular degeneration (AMD) and to evaluate VRQol according to different types of AMD.<br><br>METHODS: In this small-scale, single-center, prospective investigation, patients with AMD and subjects without any signs of macular disease were asked to complete the NEI-VFQ-39. A total of 159 subjects were included and grouped according to the type of AMD as follows: 40 patients with dry AMD in both eyes (DD), 40 patients with exudative AMD in one eye (DE), 41 patients with exudative AMD in both eyes (EE), and 38 subjects without any signs of macular disease, as a control group (CG).<br><br>RESULTS: The average age of the participants was 76&#x2009;&#xb1;&#x2009;7 years, and 44% were male. Most participants were retired (22.4%), and 75% of patients were initially diagnosed by their ophthalmologist. All the AMD groups had significantly worse overall VRQol than the CG. For general vision, near vision, mental health, and role difficulties, all the AMD groups had significantly lower scores than the CG. For distance vision, color vision, peripheral vision, driving difficulties, dependency, and social functioning, only patients in the EE and DE groups had significantly worse scores than the CG. The type of retinal fluid in patients with exudative AMD had no effect on overall VRQol; however, we found that the presence of pigment epithelial detachment could be associated with more role difficulties, such as completing work or working long hours.<br><br>CONCLUSION: All types of AMD had a negative effect on vision-related quality of life. This effect was significantly more pronounced in patients with exudative AMD in at least one eye. However, the type of retinal fluid in patients with exudative AMD had no influence on their overall vision-related quality of life.},
}
@article {pmid37672102,
year = {2024},
author = {Mauschitz, MM and Hochbein, BJ and Klinkhammer, H and Saßmannshausen, M and Terheyden, JH and Krawitz, P and Finger, RP},
title = {Prevalence and determinants of subretinal drusenoid deposits in patients' first-degree relatives.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {1},
pages = {53-60},
pmid = {37672102},
issn = {1435-702X},
mesh = {Humans ; Aged ; Aged, 80 and over ; Adult ; Middle Aged ; *Retinal Drusen/diagnosis/epidemiology/genetics ; Prevalence ; Retinal Pigment Epithelium ; Genetic Risk Score ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; },
abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) are distinct extracellular alteration anterior to the retinal pigment epithelium (RPE). Given their commonly uniform phenotype, a hereditary predisposition seems likely. Hence, we aim to investigate prevalence and determinants in patients' first-degree relatives.<br><br>METHODS: We recruited SDD outpatients at their visits to our clinic and invited their relatives. We performed a full ophthalmic examination including spectral domain-optical coherence tomography (SD-OCT) and graded presence, disease stage of SDD as well as percentage of infrared (IR) en face area affected by SDD. Moreover, we performed genetic sequencing and calculated a polygenic risk score (PRS) for AMD. We conducted multivariable regression models to assess potential determinants of SDD and associations of SDD with PRS.<br><br>RESULTS: We included 195 participants, 123 patients (mean age 81.4 &#xb1; 7.2 years) and 72 relatives (mean age 52.2 &#xb1; 14.2 years), of which 7 presented SDD, resulting in a prevalence of 9.7%. We found older age to be associated with SDD presence and area in the total cohort and a borderline association of higher body mass index (BMI) with SDD presence in the relatives. Individuals with SDD tended to have a higher PRS, which, however, was not statistically significant in the multivariable regression.<br><br>CONCLUSION: Our study indicates a potential hereditary aspect of SDD and confirms the strong association with age. Based on our results, relatives of SDD patients ought to be closely monitored for retinal alterations, particularly at an older age. Further longitudinal studies with larger sample size and older relatives are needed to confirm or refute our findings.},
}
@article {pmid37671441,
year = {2024},
author = {Azoad Ahnaf, SM and Saha, S and Frost, S and Atiqur Rahaman, GM},
title = {Understanding and interpreting CNN's decision in optical coherence tomography-based AMD detection.},
journal = {European journal of ophthalmology},
volume = {34},
number = {3},
pages = {803-815},
doi = {10.1177/11206721231199126},
pmid = {37671441},
issn = {1724-6016},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Neural Networks, Computer ; Macular Degeneration/diagnosis/diagnostic imaging ; Aged ; Algorithms ; Wet Macular Degeneration/diagnosis ; },
abstract = {INTRODUCTION: Automated assessment of age-related macular degeneration (AMD) using optical coherence tomography (OCT) has gained significant research attention in recent years. Though a list of convolutional neural network (CNN)-based methods has been proposed recently, methods that uncover the decision-making process of CNNs or critically interpret CNNs' decisions in the context are scant. This study aims to bridge this research gap.<br><br>METHODS: We independently trained several state-of-the-art CNN models, namely, VGG16, VGG19, Xception, ResNet50, InceptionResNetV2 for AMD detection and applied CNN visualization techniques, namely, Grad-CAM, Grad-CAM++, Score CAM, Faster Score CAM to highlight the regions of interest utilized by the CNNs in the context. Retinal layer segmentation methods were also developed to explore how the CNN regions of interest related to the layers of the retinal structure. Extensive experiments involving 2130 SD-OCT scans collected from Duke University were performed.<br><br>RESULTS: Experimental analysis shows that Outer Nuclear Layer to Inner Segment Myeloid (ONL-ISM) influences the AMD detection decision heavily as evident from the normalized intersection (NI) scores. For AMD cases the obtained average NI scores were respectively 13.13%, 17.2%, 9.7%, 10.95%, and 11.31% for VGG16, VGG19, ResNet50, Xception, and Inception ResNet V2, whereas, for normal cases, these values were respectively 21.7%, 21.3%, 16.85%, 10.175% and 16%.<br><br>CONCLUSION: Critical analysis reveals that the ONL-ISM is the most contributing layer in determining AMD, followed by Nerve Fiber Layer to Inner Plexiform Layer (NFL-IPL).},
}
@article {pmid37671424,
year = {2024},
author = {Cunha de Souza, E and Tombolini, B and Sacconi, R and Bandello, F and Querques, G},
title = {A Brazilian case of exudative perifoveal vascular anomalous complex responsive to aflibercept intravitreal injections.},
journal = {European journal of ophthalmology},
volume = {34},
number = {2},
pages = {NP68-NP72},
doi = {10.1177/11206721231200116},
pmid = {37671424},
issn = {1724-6016},
mesh = {Male ; Humans ; Female ; Adult ; Intravitreal Injections ; Brazil ; Placenta Growth Factor/therapeutic use ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Fluorescein Angiography/methods ; *Vascular Malformations/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {PURPOSE: To report a case of exudative perifoveal exudative vascular anomalous complex (ePVAC) in a Brazilian healthy patient that underwent a complete resolution after aflibercept intravitreal injections.<br><br>CASE DESCRIPTION: A 41-year-old healthy Brazilian man complained of acute central vision loss in his right eye (RE). Fundus examination showed a perifoveal hemorrhagic aneurysmal lesion, accompanied by several hard exudates in RE. On fluorescein angiography, these abnormalities showed a progressive hyperfluorescence with surrounding leakage. Optical coherence tomography (OCT) revealed a deep, perifoveal hyporeflective cystic space with a hyperreflective wall and hyperreflective material inside of fibrin-like aspect. Around this aneurism, intraretinal hyporeflective spaces suggestive of exudation were detected. Nor pathological flow signal, or telangiectatic dilations were evidenced on OCT-angiography. Therefore, a diagnosis of exudative ePVAC in RE was hypothesized. After an initial observation, the patient underwent three monthly aflibercept intravitreal injections (0.05&#x2005;ml/2&#x2005;mg), with a significative anatomical and functional improvement after two weeks from first dose. On last follow-up at five months from baseline, patient experienced no evidence of new exudation and a stable visual acuity.<br><br>DISCUSSION: Placental growth factor (PlGF) may impact on pericytes' dropout, and thus on ePVAC development. In contrast to the other anti-VEGF drugs, aflibercept is the only molecule contrasting PlGF. Therefore, aflibercept would act on ePVAC not as an anti-VEGF drug, but rather as an anti-PlGF one.<br><br>CONCLUSION: This report encouraged the use of aflibercept as a therapeutic option for ePVAC. Further studies are required to confirm our result and the impact of PlGF on ePVAC pathogenesis.},
}
@article {pmid37671084,
year = {2023},
author = {Zhu, RC and Li, FF and Wu, YQ and Yi, QY and Huang, XF},
title = {Minimal effect of sleep on the risk of age-related macular degeneration: a Mendelian randomization study.},
journal = {Frontiers in aging neuroscience},
volume = {15},
number = {},
pages = {1159711},
pmid = {37671084},
issn = {1663-4365},
abstract = {AIMS: Observational studies have shown that sleep pattern is associated with age-related macular degeneration (AMD), but whether sleep pattern is a causal factor for AMD remains unclear. This study aims to use Mendelian randomization (MR) analysis to investigate the potential causal relationship between sleep traits and AMD.<br><br>METHODS: This is a two-sample MR study. The single-nucleotide polymorphisms associated with AMD and early AMD were selected as the outcome from two different genome-wide association studies (GWAS): the early AMD GWAS with 14,034 cases and 91,214 controls, and AMD GWAS with 3,553 cases and 147,089 controls. The datasets of sleep duration, daytime dozing, and sleeplessness were used as exposure, which comprised nearly 0.46 million participants. Inverse-variance weighted method was used as the main result, and comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the impact of potential horizontal pleiotropy.<br><br>RESULTS: Through MR analysis, we found that sleep duration was significantly associated with AMD (OR = 0.983, 95% CI = 0.970-0.996, P-value = 0.01). We also found suggestive evidence for the association of genetically predicted sleep duration with early AMD, which showed a consistent direction of effect with a marginal significance (OR = 0.724, 95% CI = 0.503-1.041, P-value = 0.08). Sensitivity analyses further supported the robustness of the causal relationship between sleep duration and AMD. However, we were unable to determine the relationship between daytime dozing or sleeplessness and AMD (including early AMD) (P-value > 0.05).<br><br>CONCLUSION: Sleep duration affects the causal risk for AMD; that is, longer sleep duration reduces the risk of AMD, while shorter sleep duration increases the risk of AMD. Although the influence is minimal, keeping adequate sleep duration is recommended, especially for patients with intermediate or advanced AMD.},
}
@article {pmid37670143,
year = {2024},
author = {Borrelli, E and Oakley, JD and Iaccarino, G and Russakoff, DB and Battista, M and Grosso, D and Borghesan, F and Barresi, C and Sacconi, R and Bandello, F and Querques, G},
title = {Deep-learning based automated quantification of critical optical coherence tomography features in neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {38},
number = {3},
pages = {537-544},
pmid = {37670143},
issn = {1476-5454},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Deep Learning ; Retrospective Studies ; Subretinal Fluid ; *Retinal Detachment ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnostic imaging/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Intravitreal Injections ; },
abstract = {PURPOSE: To validate a deep learning algorithm for automated intraretinal fluid (IRF), subretinal fluid (SRF) and neovascular pigment epithelium detachment (nPED) segmentations in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: In this IRB-approved study, optical coherence tomography (OCT) data from 50 patients (50 eyes) with exudative nAMD were retrospectively analysed. Two models, A1 and A2, were created based on gradings from two masked readers, R1 and R2. Area under the curve (AUC) values gauged detection performance, and quantification between readers and models was evaluated using Dice and correlation (R[2]) coefficients.<br><br>RESULTS: The deep learning-based algorithms had high accuracies for all fluid types between all models and readers: per B-scan IRF AUCs were 0.953, 0.932, 0.990, 0.942 for comparisons A1-R1, A1-R2, A2-R1 and A2-R2, respectively; SRF AUCs were 0.984, 0.974, 0.987, 0.979; and nPED AUCs were 0.963, 0.969, 0.961 and 0.966. Similarly, the R[2] coefficients for IRF were 0.973, 0.974, 0.889 and 0.973; SRF were 0.928, 0.964, 0.965 and 0.998; and nPED were 0.908, 0.952, 0.839 and 0.905. The Dice coefficients for IRF averaged 0.702, 0.667, 0.649 and 0.631; for SRF were 0.699, 0.651, 0.692 and 0.701; and for nPED were 0.636, 0.703, 0.719 and 0.775. In an inter-observer comparison between manual readers R1 and R2, the R[2] coefficient was 0.968 for IRF, 0.960 for SRF, and 0.906 for nPED, with Dice coefficients of 0.692, 0.660 and 0.784 for the same features.<br><br>CONCLUSIONS: Our deep learning-based method applied on nAMD can segment critical OCT features with performance akin to manual grading.},
}
@article {pmid37669850,
year = {2024},
author = {Sadda, S and Sarraf, D and Khanani, AM and Tadayoni, R and Chang, AA and Saffar, I and Gedif, K and Wong, DT},
title = {Comparative assessment of subretinal hyper-reflective material in patients treated with brolucizumab versus aflibercept in HAWK and HARRIER.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {6},
pages = {852-858},
pmid = {37669850},
issn = {1468-2079},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration &amp; dosage ; *Recombinant Fusion Proteins/therapeutic use ; *Tomography, Optical Coherence/methods ; *Visual Acuity/physiology ; *Angiogenesis Inhibitors/therapeutic use ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Male ; Female ; Antibodies, Monoclonal, Humanized/therapeutic use ; Aged ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Double-Blind Method ; Retina/pathology/diagnostic imaging ; Treatment Outcome ; },
abstract = {PURPOSE: Post hoc analysis of the phase III HAWK and HARRIER studies to compare the reductions in subretinal hyper-reflective material (SHRM) thickness following brolucizumab 6 mg or aflibercept 2 mg treatment and to assess SHRM thickness and thickness variability as a potential biomarker of visual outcomes in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Optical coherence tomography images from the brolucizumab (n=700) and aflibercept (n=696) arms were analysed for the maximum SHRM thickness across the macula over 96 weeks. In a pooled treatment-agnostic analysis, the effect of week 12 SHRM thickness and SHRM thickness variability on best-corrected visual acuity (BCVA) through week 96 were also assessed.<br><br>RESULTS: Brolucizumab was associated with numerically higher percentage reductions from baseline in SHRM thickness versus aflibercept in all patients (week 96: 54.4% vs 47.6%, respectively) and also in the matched subgroups with disease activity at week 16 (week 96: 51.6% vs 33.8%, respectively). In eyes with lower SHRM measurements at week 12, mean BCVA gains from baseline were higher at week 96 (<200&#x2009;&#xb5;m, +6.47 Early Treatment Diabetic Retinopathy Study letters; &#x2265;200&#x2009;&#xb5;m, +3.10 letters). Eyes with the lowest SHRM thickness variability from week 12 to week 96 showed the greatest mean BCVA gains from baseline (week 96: <12&#x2009;&#xb5;m, +7.42 letters; >71&#x2009;&#xb5;m, -2.95 letters).<br><br>CONCLUSIONS: In HAWK and HARRIER, greater reductions in maximum SHRM thickness from baseline were observed with brolucizumab compared with aflibercept. Furthermore, the data suggest that SHRM thickness postloading and SHRM thickness variability over time are biomarkers for visual outcomes in patients with nAMD.},
}
@article {pmid37668741,
year = {2024},
author = {Kataoka, K and Itagaki, K and Hashiya, N and Wakugawa, S and Tanaka, K and Nakayama, M and Yamamoto, A and Mukai, R and Honjyo, J and Maruko, I and Kawai, M and Miyara, Y and Terao, N and Wakatsuki, Y and Onoe, H and Mori, R and Koizumi, H and Sekiryu, T and Iida, T and Okada, AA and , },
title = {Six-month outcomes of switching from aflibercept to faricimab in refractory cases of neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {1},
pages = {43-51},
pmid = {37668741},
issn = {1435-702X},
mesh = {Humans ; Treatment Outcome ; Follow-Up Studies ; Retrospective Studies ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; *Retinal Detachment/drug therapy ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnosis/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Antibodies, Bispecific ; },
abstract = {PURPOSE: To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections.<br><br>METHODS: This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography.<br><br>RESULTS: The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month (P = 0.013 and 0.008), although statistical significance was lost at 6 months (P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 &#xb1; 0.5 weeks at baseline to 8.7 &#xb1; 1.7 weeks at 6 months (P < 0.001) in Group 1. No clear predictors of response were identified.<br><br>CONCLUSION: Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.},
}
@article {pmid37666251,
year = {2023},
author = {Brandl, C and Finger, RP and Heid, IM and Mauschitz, MM},
title = {Age-Related Macular Degeneration in an Ageing Society - Current Epidemiological Research.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {240},
number = {9},
pages = {1052-1059},
doi = {10.1055/a-2105-1064},
pmid = {37666251},
issn = {1439-3999},
mesh = {Humans ; Cross-Sectional Studies ; Longitudinal Studies ; Europe/epidemiology ; *Macular Degeneration/diagnosis/epidemiology ; Aging ; },
abstract = {Epidemiological studies on age-related macular degeneration (AMD) provide crucial data on the frequency of early and late forms as well as associated risk factors. The increasing number of population-based cross-sectional and longitudinal cohort studies in Germany and Europe with published data is making prevalence and incidence estimators for AMD more robust, although they show mostly method-related fluctuations. This review article brings together the latest published epidemiological measures for AMD from Germany and Central as well as Western Europe. Based on this data and population figures for Germany and Europe, prevalence is projected, and future trends are forecasted. The epidemiological evidence for AMD-associated risk factors is also improving, especially through meta-analyses within large consortia with correspondingly high case numbers. This review article summarizes the latest findings and resulting recommendations for prevention approaches. Additionally, it discusses treatment options and future challenges.},
}
@article {pmid37664981,
year = {2023},
author = {Kim, S and Chae, JB and Kim, D and Park, CW and Sim, Y and Lee, H and Park, G and Lee, J and Hong, S and Jana, B and Kim, C and Chung, H and Ryu, JH},
title = {Supramolecular Senolytics via Intracellular Oligomerization of Peptides in Response to Elevated Reactive Oxygen Species Levels in Aging Cells.},
journal = {Journal of the American Chemical Society},
volume = {145},
number = {40},
pages = {21991-22008},
doi = {10.1021/jacs.3c06898},
pmid = {37664981},
issn = {1520-5126},
mesh = {Mice ; Animals ; Reactive Oxygen Species ; *Senotherapeutics ; *Cellular Senescence ; Peptides/pharmacology ; Integrins ; },
abstract = {Senolytics, which eliminate senescent cells from tissues, represent an emerging therapeutic strategy for various age-related diseases. Most senolytics target antiapoptotic proteins, which are overexpressed in senescent cells, limiting specificity and inducing severe side effects. To overcome these limitations, we constructed self-assembling senolytics targeting senescent cells with an intracellular oligomerization system. Intracellular aryl-dithiol-containing peptide oligomerization occurred only inside the mitochondria of senescent cells due to selective localization of the peptides by RGD-mediated cellular uptake into integrin αvβ3-overexpressed senescent cells and elevated levels of reactive oxygen species, which can be used as a chemical fuel for disulfide formation. This oligomerization results in an artificial protein-like nanoassembly with a stable α-helix secondary structure, which can disrupt the mitochondrial membrane via multivalent interactions because the mitochondrial membrane of senescent cells has weaker integrity than that of normal cells. These three specificities (integrin αvβ3, high ROS, and weak mitochondrial membrane integrity) of senescent cells work in combination; therefore, this intramitochondrial oligomerization system can selectively induce apoptosis of senescent cells without side effects on normal cells. Significant reductions in key senescence markers and amelioration of retinal degeneration were observed after elimination of the senescent retinal pigment epithelium by this peptide senolytic in an age-related macular degeneration mouse model and in aged mice, and this effect was accompanied by improved visual function. This system provides a strategy for the treatment of age-related diseases using supramolecular senolytics.},
}
@article {pmid37663754,
year = {2023},
author = {Liu, Q and Sun, S and Yang, Z and Shao, Y and Li, X},
title = {Serum Amyloid A 4 as a Common Marker of Persistent Inflammation in Patients with Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.},
journal = {Journal of inflammation research},
volume = {16},
number = {},
pages = {3783-3797},
pmid = {37663754},
issn = {1178-7031},
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) and its subtype, polypoidal choroidal vasculopathy (PCV), are common choroidal vasculopathies. Although they share many common clinical manifestations and treatment strategies, a lack of comprehensive analysis of these conditions means that it is difficult for researchers to further explore the common pathomechanisms of nAMD and PCV. The aim of this study was to characterize aqueous humor (AH) proteome alterations and identify a novel biomarker related to both nAMD and PCV.<br><br>METHODS: Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) was adopted to analyze the AH proteomes of nAMD, PCV and controls. The target protein was validated using the enzyme-linked immunosorbent assay (ELISA) and subjected to receiver operating characteristic (ROC) curve analysis.<br><br>RESULTS: A total of 737 different proteins were identified in all the groups, of which 544 were quantifiable. The bioinformatics analysis suggested that immune response activation is the essential event in both nAMD and PCV. Serum amyloid A (SAA) 4 is closely associated with a number of chronic inflammatory diseases, and it was enriched as the hub protein. ROC analysis showed that SAA4 could distinguish both nAMD and PCV from the controls.<br><br>CONCLUSION: This comprehensive study provides insights into, and furthers our understanding of, the pathological mechanism of nAMD and PCV. Additionally, the SAA4 level alteration may serve as a common biomarker of nAMD and PCV.},
}
@article {pmid37660150,
year = {2023},
author = {Twarog, M and Schustak, J and Xu, Y and Coble, M and Dolan, K and Esterberg, R and Huang, Q and Saint-Geniez, M and Bao, Y},
title = {TNFα induced by DNA-sensing in macrophage compromises retinal pigment epithelial (RPE) barrier function.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {14451},
pmid = {37660150},
issn = {2045-2322},
mesh = {Humans ; Tumor Necrosis Factor-alpha ; DNA ; *Nucleic Acids ; Cytokines ; *Interferon Type I ; Macrophages ; *Macular Degeneration ; },
abstract = {Increasing evidence suggests that chronic inflammation plays an important role in the pathogenesis of age-related macular degeneration (AMD); however, the precise pathogenic stressors and sensors, and their impact on disease progression remain unclear. Several studies have demonstrated that type I interferon (IFN) response is activated in the retinal pigment epithelium (RPE) of AMD patients. Previously, we demonstrated that human RPE cells can initiate RNA-mediated type I IFN responses through RIG-I, yet are unable to directly sense and respond to DNA. In this study, we utilized a co-culture system combining primary human macrophage and iPS-derived RPE to study how each cell type responds to nucleic acids challenges and their effect on RPE barrier function in a homotypic and heterotypic manner. We find that DNA-induced macrophage activation induces an IFN response in the RPE, and compromises RPE barrier function via tight-junction remodeling. Investigation of the secreted cytokines responsible for RPE dysfunction following DNA-induced macrophages activation indicates that neutralization of macrophage-secreted TNFα, but not IFNβ, is sufficient to rescue RPE morphology and barrier function. Our data reveals a novel mechanism of intercellular communication by which DNA induces RPE dysfunction via macrophage-secreted TNFa, highlighting the complexity and potential pathological relevance of RPE and macrophage interactions.},
}
@article {pmid37659709,
year = {2023},
author = {Gordon, WC and Kautzmann, MI and Jun, B and Cothern, ML and Fang, Z and Bazan, NG},
title = {Rod-specific downregulation of omega-3 very-long-chain polyunsaturated fatty acid pathway in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {235},
number = {},
pages = {109639},
pmid = {37659709},
issn = {1096-0007},
support = {R01 EY005121/EY/NEI NIH HHS/United States ; },
mesh = {Female ; Male ; Humans ; Down-Regulation ; Chromatography, Liquid ; Tandem Mass Spectrometry ; *Fatty Acids, Omega-3 ; *Macular Degeneration ; },
abstract = {Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, we compared omega-3 (n-3) fatty acid with DHA (22:6) and omega-6 (n-6) fatty acid with arachidonic acid (AA; 20:4) pathways. n-3 PC(22:6/22:6, 44:12) and n-6 PC(20:4/20:4, 40:8) showed differences among male/female, macula/periphery, and normal/AMD retinas. Periphery of AMD retina males increased 44:12 abundance, while normal females increased 40:8 (all macula had an upward 40:8 tendency). We also showed that female AMD switched from n-3 to n-6 fatty acids; most changes in AMD occurred in the periphery of female AMD retinas. DHA and VLC-PUFA release from PCs leads to conversion in pro-survival NPD1 and ELVs. The loss of the neuroprotective precursors of ELVs in the retina periphery from AMD facilitates uncompensated stress and cell loss. In AMD, the female retina loses peripheral rods VLC-PUFAs to about 33% less than in males limiting ELV formation and its protective bioactivity.},
}
@article {pmid37659600,
year = {2024},
author = {Nissen, AHK and Kiilgaard, HC and van Dijk, EHC and Hajari, JN and Huemer, J and Iovino, C and Schneider, M and Sørensen, TL and Grauslund, J and Subhi, Y},
title = {Exudative Progression of Treatment-Naïve Nonexudative Macular Neovascularization in Age-Related Macular Degeneration: A Systematic Review With Meta-Analyses.},
journal = {American journal of ophthalmology},
volume = {257},
number = {},
pages = {46-56},
doi = {10.1016/j.ajo.2023.08.020},
pmid = {37659600},
issn = {1879-1891},
mesh = {Humans ; Fluorescein Angiography/methods ; *Macular Degeneration/complications/diagnosis ; *Choroidal Neovascularization/diagnosis ; Risk Factors ; Eye ; Tomography, Optical Coherence/methods ; Retrospective Studies ; },
abstract = {PURPOSE: To systematically review and report the rate of exudative progression over time in patients with nonexudative macular neovascularization (MNV) in age-related macular degeneration (AMD).<br><br>DESIGN: Systematic review with prevalence meta-analyses and individual participant meta-analysis.<br><br>METHODS: We searched 10 literature databases on March 26, 2023, for studies of consecutive patients with treatment-na&#xef;ve nonexudative MNV in AMD. The primary outcome of interest was time from diagnosis to exudative progression. We conducted meta-analyses on the prevalence of exudative progression at 1 and 2 years. Where possible, we extracted individual participant data from studies and conducted an individual participant meta-analysis and explored the exudative progression using a time-to-event curve.<br><br>RESULTS: We identified 16 eligible studies with a total of 384 eyes with nonexudative MNV. Exudative progression had occurred in 20.9% (95% CI 13.1%-29.8%) of eyes at 1 year and in 30.7% (95% CI 21.8%-40.4%) at 2 years. Similar results were observed in the individual participant meta-analysis, showing exudative progression in 18.9% (95% CI 13.5%-26.3%) of eyes at 1 year and 31.3% (95% CI 24.2%-40.0%) at 2 years. Risk factors for a fast exudative progression were the presence of subretinal lipid globules, large MNV areas, rapid MNV growth, growth in pigment epithelium detachment height and width, appearance of a branching pattern, and development of a hyporeflective halo around the MNV.<br><br>CONCLUSIONS: Nonexudative MNVs in AMD are at high risk of exudative progression. Recognition of these lesions may allow for better individualized follow-up regimens in which closer monitoring may facilitate earlier diagnosis of exudative progression.},
}
@article {pmid37658033,
year = {2023},
author = {Garay-Aramburu, G and Rodriguez-Feijoo, D and Aldazabal-Echeveste, M and Del Barrio, Z and Eiras-Fernández, A and Piñero, DP and Larrauri-Arana, A},
title = {Predictors of stoppage and recurrence of choroidal neovascularization with a Treat- Extend-Stop protocol: 4-year follow-up.},
journal = {Journal francais d'ophtalmologie},
volume = {46},
number = {10},
pages = {1204-1211},
doi = {10.1016/j.jfo.2023.02.021},
pmid = {37658033},
issn = {1773-0597},
mesh = {Humans ; Angiogenesis Inhibitors ; Follow-Up Studies ; Treatment Outcome ; Retrospective Studies ; *Choroidal Neovascularization/diagnosis/drug therapy ; *Macular Degeneration/diagnosis ; Intravitreal Injections ; Fundus Oculi ; Tomography, Optical Coherence ; },
abstract = {OBJECTIVE: To analyze the long-term results of treatment of active age-related macular degeneration (AMD) with anti-vascular endothelial growth factor (VEGF) agents using the treat-extend-stop (TES) approach, defining predictive factors for stoppage of the treatment and recurrences in a real-world setting.<br><br>METHODS: Data from 191 eyes treated with intravitreal injections for choroidal neovascularization due to AMD were retrospectively reviewed. Changes in best-corrected visual acuity (BCVA) and membrane activity (optical coherence tomography) were recorded and evaluated over a 48-month follow-up. Logistic regression analysis was used to determine predictors of treatment stoppage and recurrences after stoppage.<br><br>RESULTS: BCVA improvement was found in 70.5% of eyes at 48 months, and remaining signs of activity in 27.9%. Disease inactivity was achieved in 69 eyes (31.9%), with a relapse of the membrane in 29 of these eyes (42.0%). Significant independent predictors of treatment stoppage were found: no foveal membrane, inactive membrane at 12, 24, 36 and 48 months, extension interval>8 weeks at 12 and 24 months,>15 injections at 24 months, and baseline BCVA>61 letters. Concerning recurrent membranes, only the presence of membrane activity at 36 months and baseline BCVA>61 letters were independent predictors.<br><br>CONCLUSIONS: Anti-VEGF treatment of AMD using the TES protocol allows for successful visual restoration in most patients, with more likely disease inactivity in those eyes with better baseline BCVA, maintaining signs of membrane inactivity during the first two years of follow-up and requiring fewer injections.},
}
@article {pmid37657753,
year = {2023},
author = {Rathi, S and Hasan, R and Ueffing, M and Clark, SJ},
title = {Therapeutic targeting of the complement system in ocular disease.},
journal = {Drug discovery today},
volume = {28},
number = {11},
pages = {103757},
doi = {10.1016/j.drudis.2023.103757},
pmid = {37657753},
issn = {1878-5832},
mesh = {Humans ; *Macular Degeneration/drug therapy ; Eye ; *Geographic Atrophy/drug therapy/etiology/pathology ; },
abstract = {The complement system is involved in the pathogenesis of several ocular diseases, providing a rationale for the investigation of complement-targeting therapeutics for these conditions. Dry age-related macular degeneration, as characterised by geographic atrophy (GA), is currently the most active area of research for complement-targeting therapeutics, with a complement C3 inhibitor approved in the United States earlier this year marking the first approved therapy for GA. This review discusses the role of complement in ocular disease, provides an overview of the complement-targeting agents currently under development for ocular conditions, and reflects on the lessons that can be learned from the preclinical investigations and clinical trials conducted in this field to date.},
}
@article {pmid37657710,
year = {2024},
author = {Hall, J and Daniszewski, M and Cheung, S and Shobhana, K and Kumar, H and Liang, HH and Beetham, H and Cho, E and Abbott, C and Hewitt, AW and Simpson, KJ and Guymer, RH and Paull, D and Pébay, A and Lidgerwood, GE},
title = {A semi-automated pipeline for quantifying drusen-like deposits in human induced pluripotent stem cell-derived retinal pigment epithelium cells.},
journal = {SLAS technology},
volume = {29},
number = {3},
pages = {100106},
doi = {10.1016/j.slast.2023.08.006},
pmid = {37657710},
issn = {2472-6311},
mesh = {Humans ; *Induced Pluripotent Stem Cells/cytology ; *Retinal Pigment Epithelium/pathology ; *Retinal Drusen/pathology ; Macular Degeneration/pathology/diagnosis ; Image Processing, Computer-Assisted/methods ; Microscopy, Confocal/methods ; },
abstract = {Age-Related Macular Degeneration (AMD) is a highly prevalent form of retinal disease amongst Western communities over 50 years of age. A hallmark of AMD pathogenesis is the accumulation of drusen underneath the retinal pigment epithelium (RPE), a biological process also observable in vitro. The accumulation of drusen has been shown to predict the progression to advanced AMD, making accurate characterisation of drusen in vitro models valuable in disease modelling and drug development. More recently, deposits above the RPE in the subretinal space, called reticular pseudodrusen (RPD) have been recognized as a sub-phenotype of AMD. While in vitro imaging techniques allow for the immunostaining of drusen-like deposits, quantification of these deposits often requires slow, low throughput manual counting of images. This further lends itself to issues including sampling biases, while ignoring critical data parameters including volume and precise localization. To overcome these issues, we developed a semi-automated pipeline for quantifying the presence of drusen-like deposits in vitro, using RPE cultures derived from patient-specific induced pluripotent stem cells (iPSCs). Using high-throughput confocal microscopy, together with three-dimensional reconstruction, we developed an imaging and analysis pipeline that quantifies the number of drusen-like deposits, and accurately and reproducibly provides the location and composition of these deposits. Extending its utility, this pipeline can determine whether the drusen-like deposits locate to the apical or basal surface of RPE cells. Here, we validate the utility of this pipeline in the quantification of drusen-like deposits in six iPSCs lines derived from patients with AMD, following their differentiation into RPE cells. This pipeline provides a valuable tool for the in vitro modelling of AMD and other retinal disease, and is amenable to mid and high throughput screenings.},
}
@article {pmid37656449,
year = {2023},
author = {Chan, CK and Beaulieu, WT and Lujan, BJ and Lalezary, M and Lent-Schochet, D and Lo, T and Yiu, G},
title = {Impact of Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration on Eyes With Intermediate Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {9},
pages = {1},
pmid = {37656449},
issn = {2164-2591},
support = {R01 EY032238/EY/NEI NIH HHS/United States ; R21 EY031108/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Child, Preschool ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Prospective Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Retina/diagnostic imaging ; *Geographic Atrophy ; },
abstract = {PURPOSE: The purpose of this study was to determine the impact of prophylactic ranibizumab (PR) injections given every 3 months in eyes with intermediate nonexudative age-related macular degeneration (AMD) on drusen volume, macular layer thicknesses, and progression of geographic atrophy (GA) area over 24 months in the PREVENT trial.<br><br>METHODS: This post hoc analysis of the prospective PREVENT trial compared eyes with intermediate AMD randomized to PR versus sham injections to determine rates of conversion to neovascular AMD over 24&#xa0;months. Drusen area and volume, macular thickness and volume, and retinal layer thicknesses were measured on spectral-domain optical coherence tomography images and analyzed. Masked grading of GA area and subretinal drusenoid deposits (SDDs) using fundus autofluorescence images was performed.<br><br>RESULTS: There were no statistical differences in drusen area and volumes between groups, and similar reductions in central subfield thickness, mean cube thickness, cube volume, and retinal sublayer thickness from baseline to 24&#xa0;months (P = 0.018 to < 0.001), with no statistical differences between groups in any of these anatomic parameters. These findings were not impacted by the presence or absence of SDD. Among the 9&#xa0;eyes with GA in this study, mean GA growth rate from baseline to 24&#xa0;months was 1.34 +/- 0.79&#xa0;mm2/year after PR and 1.95 +/- 1.73&#xa0;mm2/year in sham-treated eyes (P = 0.49), and similarly showed no statistical difference with square root transformation (P = 0.61).<br><br>CONCLUSIONS: Prophylactic ranibizumab given every 3&#xa0;months did not appear to affect drusen volume, macular thinning, or GA progression in eyes with intermediate AMD.<br><br>TRANSLATIONAL RELEVANCE: This work investigates the impact of PR on progressive retinal degeneration in a clinical trial.},
}
@article {pmid37653781,
year = {2023},
author = {Lu, Q and Sun, M and Cao, J and Wang, W and Wang, H and Gao, Y and Wang, Y and Guo, X and Yang, W and Wang, H},
title = {Acupuncture is an effective therapy for macular damage: A case report.},
journal = {Medicine},
volume = {102},
number = {34},
pages = {e34735},
pmid = {37653781},
issn = {1536-5964},
mesh = {Humans ; Female ; Child ; *Acupuncture Therapy ; Eye ; *Macular Degeneration ; *Medicine ; *Drug-Related Side Effects and Adverse Reactions ; },
abstract = {RATIONALE: Many factors can contribute to the development of macular injury, which results in vision loss as a result of a disease. Heredity, age, underlying eye illness, internal eye surgery, or eye trauma can all cause it. A safer alternative to current therapies for macular degeneration is urgently needed since they all induce ocular irritation and postoperative recurrence as well as a host of other adverse effects.<br><br>PATIENT CONCERNS: A 12-year-old girl was the patient. A laser pen burnt her right eye. There was a spot and a shadow in the middle of her right eye's visual field.<br><br>DIAGNOSES: Macular degeneration.<br><br>INTERVENTIONS: Given the patient's age, we opted out of medicine and instead used acupuncture as a symptomatic treatment.<br><br>OUTCOMES: Two months after therapy concluded, optical coherence tomography result report indicate that the macula region of the right eye is better than it was previously. The corrected visual acuity of the right eye recovered from 0.25 to 1.0, and the clinical accompanying symptoms of the right eye disappeared.<br><br>LESSONS: No additional medication or surgical procedure was employed in this instance. We treated the macular damage with acupuncture, which relieved the patient's clinical symptoms and had no adverse effects. This demonstrates that acupuncture may be beneficial in treating ophthalmopathy in this direction.},
}
@article {pmid37653561,
year = {2023},
author = {Zhang, S and Ghalandari, B and Wang, A and Li, S and Chen, Y and Wang, Q and Jiang, L and Ding, X},
title = {Superparamagnetic Composite Nanobeads Anchored with Molecular Glues for Ultrasensitive Label-free Proteomics.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {62},
number = {45},
pages = {e202309806},
doi = {10.1002/anie.202309806},
pmid = {37653561},
issn = {1521-3773},
mesh = {Humans ; *Proteomics/methods ; *Proteins ; Peptides ; Mass Spectrometry/methods ; Magnetic Iron Oxide Nanoparticles ; Proteome/analysis ; },
abstract = {Mass spectrometry has emerged as a mainstream technique for label-free proteomics. However, proteomic coverage for trace samples is constrained by adsorption loss during repeated elution at sample pretreatment. Here, we demonstrated superparamagnetic composite nanoparticles functionalized with molecular glues (MGs) to enrich proteins in trace human biofluid. We showed high protein binding (>95 %) and recovery (≈90 %) rates by anchor-nanoparticles. We further proposed a Streamlined Workflow based on Anchor-nanoparticles for Proteomics (SWAP) method that enabled unbiased protein capture, protein digestion and pure peptides elution in one single tube. We demonstrated SWAP to quantify over 2500 protein groups with 100 HEK 293T cells. We adopted SWAP to profile proteomics with trace aqueous humor samples from cataract (n=15) and wet age-related macular degeneration (n=8) patients, and quantified ≈1400 proteins from 5 μL aqueous humor. SWAP simplifies sample preparation steps, minimizes adsorption loss and improves protein coverage for label-free proteomics with previous trace samples.},
}
@article {pmid37652091,
year = {2023},
author = {Marquina, S and Ozgul, M and Robertson-Brown, K and Kenney, MC},
title = {A review on PLGA particles as a sustained drug-delivery system and its effect on the retina.},
journal = {Experimental eye research},
volume = {235},
number = {},
pages = {109626},
doi = {10.1016/j.exer.2023.109626},
pmid = {37652091},
issn = {1096-0007},
support = {R01 EY027363/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Retina ; Drug Delivery Systems ; Drug Carriers ; *Wet Macular Degeneration/drug therapy ; RNA ; },
abstract = {In this review, the designs and recent developments of polymer-based drug delivery of Poly(lactic-co-glycolic acid) (PLGA) will be discussed for the possible treatment of age-related macular degeneration (AMD). PLGA is a versatile co-polymer that consists of synthetic lactic acid and glycolic acid monomers that are constructed to produce nanoparticles, microparticles, and scaffolds for the intraocular delivery of various drugs. As an FDA-approved polymer, PLGA has historically been well-suited for systemic slow-sustained release therapies due to its performance in biodegradability and biocompatibility. This review will examine recent in vitro and in vivo studies that provide evidence for PLGA-based particles as a therapeutic drug carrier for the treatment of AMD. Anti-angiogenic and antiproliferative effects of small peptides, small molecules, RNA molecules, and proteins within PLGA particles are briefly discussed. AMD is a leading cause of central vision loss in people over 55 years and the number of those afflicted will rise as the aging population increases. AMD has two forms that are often sequential. Dry AMD and wet AMD account for 85-90% and 10-15% of cases, respectively. The distinct categories of PLGA-based drug delivery vehicles are important for dispensing novel small molecules, RNA molecules, peptides, and proteins as a long-term effective treatment of AMD.},
}
@article {pmid37648551,
year = {2024},
author = {Queguiner, F and Bezirganyan, K and Courjaret, JC and Curel, L and Penaranda, G and Bonomini, J and Righini Chossegros, M},
title = {Reliability of self-measurement of visual acuity in AMD patients with two electronic devices based on the ETDRS chart: A randomized study.},
journal = {Journal francais d'ophtalmologie},
volume = {47},
number = {1},
pages = {103911},
doi = {10.1016/j.jfo.2023.04.006},
pmid = {37648551},
issn = {1773-0597},
mesh = {Male ; Humans ; Female ; Aged ; Aged, 80 and over ; Prospective Studies ; Reproducibility of Results ; Visual Acuity ; *Macular Degeneration/diagnosis ; Vision Tests/methods ; Tablets ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) requires continuous visual acuity (VA) monitoring, increasing the burden on the health care system. Self-measurement VA tests are available on various devices. However, none of them have been based on an internationally validated benchmark chart, such as that of the Early Treatment Diabetic Retinopathy Study (ETDRS). The goal of this study was to assess the reliability of two digitized ETDRS charts adapted to two electronic devices for self-measurement of VA.<br><br>MATERIAL AND METHODS: A prospective, single-center, 1:1 randomized, two-arm, parallel group trial was conducted. The main objective was to compare VA variation as conventionally measured on a 4-m ETDRS chart versus self-measured with digitized ETDRS charts in patients treated for AMD. At each visit, conventional measurement and patient self-measurement, either on a computer at 80-cm (arm 1) or on a tablet at 40-cm (arm 2), were performed.<br><br>RESULTS: Eighty patients were included (25 men, 55 women, mean age 81.3&#xb1;7.4 years). No significant differences were observed between VA variation, conventionally measured and self-measured on a computer (arm 1; P=0.914) or tablet (arm 2; P=0.913).<br><br>CONCLUSION: These results confirm the reliability of these two methods for self-measurement of VA, and will lead to the development of a wider "telemedicine" project extended to self-measurement of VA in various pathologies.},
}
@article {pmid37648064,
year = {2024},
author = {Peterson, CL and Yap, CL and Tan, TF and Tan, LLY and Sim, KT and Ong, L and Tan, ZK and Tan, YW and Man, R and Fenwick, E and Cheung, G and Lamoureux, E and Tan, ACS},
title = {Monocular and Binocular Visual Function Assessments and Activities of Daily Living Performance in Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {1},
pages = {32-41},
doi = {10.1016/j.oret.2023.08.013},
pmid = {37648064},
issn = {2468-6530},
mesh = {Humans ; *Activities of Daily Living ; Visual Acuity ; Case-Control Studies ; Vision, Binocular ; *Macular Degeneration/diagnosis ; },
abstract = {PURPOSE: To evaluate the relationship between specific monocular and binocular visual function (VF) assessments with binocularly performed activities of daily living task tests (ADLTTs) in patients with age-related macular degeneration (AMD) and healthy controls.<br><br>DESIGN: Prospective case-control cohort study.<br><br>SUBJECTS: Thirty-six AMD patients and 36 controls.<br><br>METHOD: Visual field assessments included monocular and binocular best-corrected visual acuity (BCVA), contrast sensitivity (CS), and monocular microperimetry testing for mean macula sensitivity, mean retina sensitivity (MRS), fixation area, and fixation distance from fovea (FDF). Age-related macular degeneration lesion area and sensitivity were measured on OCT and microperimetry, respectively. Participants performed 4 validated ADLTTs with binocular BCVA: (1) reading; (2) item-search; (3) money-counting; and (4) multi-step drink-making tasks.<br><br>MAIN OUTCOME MEASURES: Spearman correlations and multivariate regression analysis, adjusted for age, sex, and potential correlation between the 2 eyes, were used to assess the relationship between monocular and binocular VF assessments, and ADLTT performance in both groups.<br><br>RESULTS: Age-related macular degeneration patients had poorer VF (BCVA, CS, mean macula sensitivity, and MRS) compared with healthy controls. Monocular BCVA in both better- and worse-vision eyes was moderately correlated with the binocular reading speed and money-counting tasks in participants with AMD. In AMD, monocular worse eye CS, MRS, AMD lesion area on OCT, and lesion sensitivity on microperimetry showed moderate correlations to various ADLTTs, such as reading, money-counting, and drink-making. Similar findings were found in our AMD cohort on multivariate regression analysis. Fewer significant correlations were observed for the better-vision eye, whereas no correlations were observed for healthy controls between VF parameters and ADLTTs. In contrast, significant associations were observed between binocular BCVA and CS with binocular ADLTTs (reading and item-search tasks) but not in AMD patients.<br><br>CONCLUSION: Although monocular BCVA remains the most common measure of VF, CS and microperimetry testing also show significant correlations with ADLTTs performance in AMD patients, and should be considered as complimentary VF-outcome measures in both clinical and research settings. Unlike healthy subjects, AMD patients do not rely on binocular VF for ADLTT function, with the worse-vision eye impacting binocular ADLTT function more than the better-vision eye. Therefore, the worse-vision eye should not be neglected during the management of AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37643039,
year = {2023},
author = {Uemura, A and Hamada, T and Mihara, N and Yamakiri, K},
title = {DEVELOPMENT OF FOCAL CHOROIDAL EXCAVATION AFTER ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.},
journal = {Retinal cases &amp; brief reports},
volume = {17},
number = {5},
pages = {538-541},
doi = {10.1097/ICB.0000000000001240},
pmid = {37643039},
issn = {1937-1578},
mesh = {Male ; Humans ; Middle Aged ; *Endothelial Growth Factors ; Polypoidal Choroidal Vasculopathy ; *Retinal Detachment ; Angiography ; Choroid ; },
abstract = {PURPOSE: The purpose of this study was to describe a case of polypoidal choroidal vasculopathy, showing a newly developed focal choroidal excavation during a 4-year follow-up period with multiple intravitreal antivascular endothelial growth factor injections.<br><br>METHODS: This study was a case report.<br><br>RESULTS: A 64-year-old man was referred for treatment of age-related macular degeneration in his left eye. His corrected visual acuity at initial presentation was 20/20 in both the right and left eye. Optical coherence tomography of the left eye revealed a steep retinal pigment epithelial detachment and subretinal fluid, and indocyanine green angiography confirmed a polypoidal lesion, leading to the diagnosis of polypoidal choroidal vasculopathy with pachychoroid features. Thereafter, antivascular endothelial growth factor intravitreal injections were continued on a pro re nata basis. Two years after the initial presentation, the sharp pigment epithelial detachment began to shrink, and a novel focal choroidal excavation gradually emerged surrounding the pigment epithelial detachment with an inner choroidal layer attenuation.<br><br>CONCLUSION: Multiple antivascular endothelial growth factor injections for polypoidal choroidal vasculopathy resulted in atrophy of the polypoidal lesion and a decrease in the blood flow in the adjacent inner choroidal vasculature, leading to the formation of a novel focal choroidal excavation.},
}
@article {pmid37641789,
year = {2022},
author = {Sigalingging, T and Perdamaian, ABI and Romdhoniyyah, DF and Prayogo, ME and Wardhana, FS and Widayanti, TW and Sasongko, MB and Agni, AN and Oka, C and Supanji, S},
title = {rs10737680 polymorphism in complement factor H and neovascular age-related macular degeneration in Yogyakarta, Indonesia.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {11},
number = {2},
pages = {71-76},
pmid = {37641789},
issn = {2322-3219},
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is one of the main causes of blindness in developed countries. Complement factor H (CFH) is one of the genes involved in the pathogenesis of nAMD. This study investigated the rs10737680 polymorphism in CFH and its conferred susceptibility to nAMD in Yogyakarta, Indonesia.<br><br>METHODS: This case-control hospital-based study recruited participants consisting of 96 patients with nAMD and 101 controls without nAMD from the Eye Polyclinic of Sardjito Hospital, YAP Eye Hospital, and Hardjolukito Hospital Yogyakarta. nAMD was diagnosed when fundus examination, fundus photographs, and optical coherence tomography revealed hard or soft drusen in the macular area measuring > 63 &#xb5;m that appeared below the retinal pigment epithelium, with or without macular hypo- or hyperpigmentation, and was accompanied by choroidal neovascularization. Genomic DNA was extracted using a commercial DNA isolation kit. The restriction fragment length polymorphism technique was used to identify the rs10737680 polymorphism in CFH.<br><br>RESULTS: The mean (standard deviation [SD]) age of the nAMD group was not homogeneous with that of the control group (P < 0.05); 65.41 (9.74) years versus 68.24 (7.82) years. The number of patients with hypertension in the nAMD group was significantly higher than in the control group (P < 0.05). In the nAMD group, the genotype distribution indicated homozygous risk allele in 34.38%, heterozygous risk allele in 57.29%, and homozygous non-risk allele in 8.33%. In the control group, the genotype distribution indicated homozygous risk allele in 21.78%, heterozygous risk allele in 36.63%, and homozygous non-risk allele in 41.58%. Statistical analysis between the two study groups according to homozygous risk allele genotype (odds ratio [OR], 7.87; 95% confidence interval [CI], 2.88-22.79) and heterozygous genotype (OR, 7.80; 95% CI, 3.11-21.19) showed a significant difference (both P < 0.01).<br><br>CONCLUSIONS: Homozygous risk allele was less frequent than heterogeneous risk allele in patients with nAMD; however, both increased the risk for nAMD. Although the homozygous or heterozygous risk-alleles were detected in most patients, yet other important genetic or environmental factors could be involved in the pathogenesis of nAMD. Overall, we found a significant association between rs10737680 polymorphism in CFH and the susceptibility to nAMD in Yogyakarta, Indonesia; however, future studies are needed to fully delineate the mechanism.},
}
@article {pmid37641639,
year = {2022},
author = {Mansour, AM and Tripathy, K and Parodi, MB},
title = {A hypothetical therapeutic effect of light peripheral panretinal photocoagulation in neovascular age-related macular degeneration.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {11},
number = {3},
pages = {137-143},
pmid = {37641639},
issn = {2322-3219},
abstract = {BACKGROUND: Vascular endothelial growth factor (VEGF) is a significant modulator of ocular angiogenesis, including that of neovascular age-related macular degeneration (nAMD). Intravitreal injection of anti-VEGF is the benchmark treatment for most retinal vascular diseases, including nAMD, diabetic maculopathy, and macular edema secondary to retinal venous occlusion. Anti-VEGF treatment is a high-frequency, time-consuming, non-cost-effective therapy, especially in countries and regions with limited resources. This treatment is easily restricted, and in practice, maintaining long-term periodic care is challenging for patients.<br><br>HYPOTHESIS: Light peripheral panretinal photocoagulation (PPRP) is applied in a mild form (barely visible mild light gray mark) anterior to the equator so as not to jeopardize the visual field. PPRP lessens the ischemia that causes neovascularization and decreases the metabolic demand in the peripheral retina. PPRP reduces serum angiopoietin-2 and VEGF levels in patients with type 2 diabetes mellitus with proliferative diabetic retinopathy. We propose using light PPRP to suppress VEGF secretion, aiming to attenuate the VEGF drive and halt choroidal neovascular growth in eyes with nAMD. Our regimen is based on two concepts: first, nAMD is a diffuse or generalized disease that affects the posterior segment; and second, PPRP is very effective in regressing diabetic retinopathy. PPRP has reportedly been successful in cases of macular edema (diabetic or following venous occlusion) resistant to VEGF antagonists. Light PPRP may be used as prophylaxis, adjunctive treatment, or monotherapy in nAMD when intravitreal injections of VEGF antagonists are not feasible.<br><br>CONCLUSIONS: The established light PPRP therapy could be promising as a one-time, cost-effective therapy or prophylaxis in patients with nAMD or at high risk. This proposed modality could be suitable for patients who have injection phobia or prefer a one-time affordable therapy to the long-term monthly visits to retinologists. Future trials are necessary to verify the safety and efficacy of this proposed treatment modality in selected patients with nAMD.},
}
@article {pmid37638581,
year = {2023},
author = {Yusef, YN and Budzinskaya, MV and Plyukhova, AA},
title = {[Faricimab: from research to clinical practice].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {4},
pages = {115-120},
doi = {10.17116/oftalma2023139041115},
pmid = {37638581},
issn = {0042-465X},
mesh = {Humans ; Ranibizumab ; *Diabetic Retinopathy/diagnosis/drug therapy ; *Macular Edema/diagnosis/drug therapy/etiology ; Vascular Endothelial Growth Factor A ; Immunoglobulin G ; },
abstract = {Development of new molecules for anti-angiogenic therapy pursues the following objectives: to increase the interval between injections, which can reduce the treatment burden; to improve the effectiveness of treatment by affecting various links of pathogenesis; to ensure a good safety profile. Faricimab is a humanized immunoglobulin G antibody that targets two key angiogenesis sites: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2). In the STAIRWAY clinical trial, faricimab was shown to produce similar results to monthly ranibizumab at longer intervals and fewer intravitreal injections in patients with neovascular age-related macular degeneration, specifically in terms of visual preservation and reduction in central retinal thickness (CRT). In the BOULEVARD trial, which lasted 36 weeks, the severity of diabetic retinopathy according to DRSS improved in previously untreated patients with diabetic macular edema by two stages and more in 12.2% of the 0.3 mg ranibizumab group, in 27.7% of patients in the 1.5 mg faricimab group, and in 38.6% of patients in the group treated with 6.0 mg faricimab. In the TENAYA, as well as LUCERNE, YOSEMITE and RHINE trials, the increase in best-corrected visual acuity (BCVA) from baseline in the faricimab group was comparable to that in the aflibercept group. Real clinical practice showed an increase in BCVA from 59.5 to 60.6 letters (p=0.035) due to a decrease in CRT from 334.3 to 303.3 µm (p=0.001). The first published studies are now appearing, and their results correspond to the clinical trials, which indicates a stable effect of the drug and the prospects for use in a large cohort of patients.},
}
@article {pmid37637949,
year = {2023},
author = {Jurja, S and Negreanu-Pirjol, T and Vasile, M and Hincu, MM and Coviltir, V and Negreanu-Pirjol, BS},
title = {Xanthophyll pigments dietary supplements administration and retinal health in the context of increasing life expectancy trend.},
journal = {Frontiers in nutrition},
volume = {10},
number = {},
pages = {1226686},
pmid = {37637949},
issn = {2296-861X},
abstract = {INTRODUCTION: Medicine faces nowadays the trend of increasing life expectancy of human population, with the resulting increase of degenerative age related diseases prevalence, combined with the risks of less tempered sun radiations environment exposure. Under these circumstances, our work pointed out on evaluating the effect of some xanthophyll pigments dietary supplements, actually widely recommended, for prevention of retinal degenerative damages and for slowing down the progression of such age related changes if they have already occurred. These dietary supplements are already well known for their total antioxidant activity, proven by photochemiluminescence method using Total Antioxidant Capacity in Lipid soluble-substances procedure.<br><br>MATERIALS AND METHODS: The study recruited a number of 120 subjects equally divided on genders. The lot included a first group of 60 patients with comparable ages (all of them over 50 years and divided in 2 segments of age: 50-60 and over 60) and suffering from comparable retinal age-related degenerative abnormalities (mild/medium severity age-related macular degeneration according to Wisconsin Age-Related Maculopathy Grading System), and a second group, considered control, including a similar number of healthy, normal retina subjects belonging to same age and gender categories. There were evaluated at baseline the eye medical status and the retinal risk by specific methods: complete eye check-up, Amsler grid, specific standardized questionnaires focused on visual function and its impact on the quality of current life. Both groups, patients and control, received similar dosages of xanthophyll pigments dietary supplements including lutein and zeaxanthin during 18 months after baseline; at the end of this supplementation period a new evaluation was conducted. In the second part of the research all subjects involved received a new dietary supplement in which the same xanthophylls were enriched with C and E vitamins and oligo-elements Zinc and Copper. At the end of three years duration supplementation, the subjects were reevaluated and the paper presents the conclusions on the matter, pointing on the impact of xanthophyll supplements on visual health.<br><br>RESULTS: Correlation tests were applied to the complete set of data. Correlation tests have values between -1 and +1. The value -1 represents the negative correlation (reverse proportionality) meanwhile the value +1 represents the positive correlation (direct proportionality). The charts show the curves that are fitting experimental data. The dependence is linear in nature, and the value R2, as it approaches more the value 1, represents a better match with the experimental data (the data are in a percentage of approximately 99% on these straight lines of type y = ax + b). In the charts, there were noted the average values of the scores for healthy control patients with "Control", and the average values of the scores for the patients with existing age related degenerative retinal pathology at baseline with "Patients".<br><br>DISCUSSION: The retinal function and the impact of visual condition on health were both evaluated at baseline, 18 months and 36 months after baseline, by visual acuity, ophthalmoscopy fundus examination, Amsler test and by asking the subjects to answer the visual function questionnaires: EQ-5D, NEI-VFQ-25, as measures of health status quality and of the influence on welfare. The study revealed that under supplementation both control healthy subjects and patients with known degenerative retinal pathology included in the 50-60 years of age group evolved almost the same way, leading to the conclusion that administered xanthophyll pigments-based supplements, simple or enriched, managed to slow down the progression of abnormal degenerative vision loss to a rate comparable to physiological aging-related vision loss. It was also observed that intake of xanthophyll pigments dietary supplements preserved the general health condition and maintained relatively constant vision on the entire 36th months follow-up research duration in patients presented with existing age related degenerative retinal pathology at baseline. For healthy subjects, evaluation showed an improvement in results after dietary supplementation, with maintenance of constant vision and a significantly increase of general condition, in a positive sense. For subjects over the age of 60 dietary supplements intake was even more effective compared to younger group in providing better control of degenerative processes.},
}
@article {pmid37637380,
year = {2023},
author = {Iqball, S and Beck, DK and Devarajan, G and Khoo, CP and O'Connor, DM and Ellis, S and Guzman, E and Mitrophanous, KA and Lad, Y},
title = {Lentiviral delivered aflibercept OXB-203 for treatment of neovascular AMD.},
journal = {Molecular therapy. Methods &amp; clinical development},
volume = {30},
number = {},
pages = {350-366},
pmid = {37637380},
issn = {2329-0501},
abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in the aging population, with vascular endothelial growth factor (VEGF) playing a key role. Treatment with recombinant anti-VEGFs is the current standard of care; however, it is only effective for 1-2 months at a time and requires re-administration. Gene therapy could pave the way for stable, long-term expression of therapeutic anti-VEGF with a single dose, reducing the frequency of treatment and potentially improving clinical outcomes. As such, we have developed OXB-203, a lentiviral-based gene therapy encoding the anti-VEGF protein aflibercept. Aflibercept derived from OXB-203 exhibited comparable in vitro binding characteristics to VEGF as recombinant aflibercept. Furthermore, its biological potency was demonstrated by the equivalent inhibition of VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and tubule formation as recombinant aflibercept. In a rat choroidal neovascularization (CNV) model of nAMD, a single subretinal administration of OXB-203 reduced laser-induced CNV lesion areas analogous to an intravitreal bolus of recombinant aflibercept. Finally, in a head-to-head comparative study, aflibercept derived from OXB-203 was shown to be expressed at significantly higher levels in ocular tissues than from an AAV8-aflibercept vector following a single subretinal delivery to rats. These findings support the therapeutic potential of OXB-203 for the management of nAMD.},
}
@article {pmid37634759,
year = {2024},
author = {He, W and Han, X and Ong, JS and Wu, Y and Hewitt, AW and Mackey, DA and Gharahkhani, P and MacGregor, S},
title = {Genome-Wide Meta-analysis Identifies Risk Loci and Improves Disease Prediction of Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {131},
number = {1},
pages = {16-29},
doi = {10.1016/j.ophtha.2023.08.023},
pmid = {37634759},
issn = {1549-4713},
mesh = {Humans ; *Genome-Wide Association Study ; Proteins/genetics ; Longitudinal Studies ; Risk Factors ; Canada/epidemiology ; *Macular Degeneration/diagnosis/genetics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; },
abstract = {PURPOSE: To identify age-related macular degeneration (AMD) risk loci and to establish a polygenic prediction model.<br><br>DESIGN: Genome-wide association study (GWAS) and polygenic risk score (PRS) construction.<br><br>PARTICIPANTS: We included 64 885 European patients with AMD and 568 740 control participants (with overlapped samples) in the UK Biobank, Genetic Epidemiology Research on Aging (GERA), International AMD Consortium, FinnGen, and published early AMD GWASs in meta-analyses, as well as 733 European patients with AMD and 20 487 control participants from the Canadian Longitudinal Study on Aging (CLSA) and non-Europeans from the UK Biobank and GERA for polygenic risk score validation.<br><br>METHODS: A multitrait meta-analysis of GWASs comprised 64 885 patients with AMD and 568 740 control participants; the multitrait approach accounted for sample overlap. We constructed a PRS for AMD based on both previously reported as well as unreported AMD loci. We applied the PRS to nonoverlapping data from the CLSA.<br><br>MAIN OUTCOME MEASURES: We identified several single nucleotide polymorphisms associated with AMD and established a PRS for AMD risk prediction.<br><br>RESULTS: We identified 63 AMD risk loci alongside the well-established AMD loci CFH and ARMS2, including 9 loci that were not reported in previous GWASs, some of which previously were linked to other eye diseases such as glaucoma (e.g., HIC1). We applied our PRS to nonoverlapping data from the CLSA. A new PRS was constructed using the PRS method, PRS-CS, and significantly improved the prediction accuracy of AMD risk compared with PRSs from previously published datasets. We further showed that even people who carry all the well-known AMD risk alleles at CFH and ARMS2 vary considerably in their AMD risk (ranging from close to 0 in individuals with low PRS to > 50% in individuals with high PRS). Although our PRS was derived in individuals of European ancestry, the PRS shows potential for predicting risk in people of East Asian, South Asian, and Latino ancestry.<br><br>CONCLUSIONS: Our findings improve the knowledge of the genetic architecture of AMD and help achieve better accuracy in AMD prediction.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37634060,
year = {2023},
author = {Britten-Jones, AC and Markakis, D and Guymer, RH and Lin, ML and Skalicky, S and Ayton, LN and Mack, HG},
title = {Characterising the diagnosis of genetic maculopathies in a real-world private tertiary retinal practice in Australia: protocol for a retrospective clinical audit.},
journal = {Annals of medicine},
volume = {55},
number = {2},
pages = {2250538},
pmid = {37634060},
issn = {1365-2060},
mesh = {Humans ; Retrospective Studies ; *Macular Degeneration/diagnosis/genetics ; Australia ; Clinical Audit ; Atrophy ; },
abstract = {PURPOSE: Accurate diagnosis of macular atrophy is paramount to enable appropriate treatment when novel treatments for geographic atrophy and macular dystrophies become available. Genetic testing is useful in distinguishing between the two conditions but is not feasible for the majority of patients in real-world clinical practice. Therefore, we aimed to investigate the potential misdiagnosis of inherited macular dystrophy as age-related macular degeneration (AMD) in real-world ophthalmic practice to assist in the development of guidelines to improve diagnostic accuracy while minimizing genetic testing for targeted patients.<br><br>METHODS: Retrospective review of the medical records of patients diagnosed with AMD, which included imaging, between 1995 and 2023 from a large multidisciplinary private ophthalmic practice in Australia. We will use a stepwise method to screen for probable cases of macular dystrophy, followed by a consensus review by an expert panel. The outcomes are (1) to determine the potential misdiagnosis rate of macular dystrophy as atrophic AMD by retinal specialists and general ophthalmologists; (2) to identify clinical imaging modalities that are most useful for differentiating macular dystrophy from atrophic AMD; and (3) to establish preliminary guidance for clinicians to improve the diagnosis of macular atrophy from AMD in practice, and thereby target cost-efficient genetic testing.<br><br>DISCUSSION: Improving the diagnostic accuracy of both AMD and macular dystrophy, while ensuring cost-efficient genetic testing, will improve the targeted treatment of macular diseases when emerging treatments become available.},
}
@article {pmid37633363,
year = {2023},
author = {Bendicho-Lavilla, C and Seoane-Viaño, I and Santos-Rosales, V and Díaz-Tomé, V and Carracedo-Pérez, M and Luzardo-Álvarez, AM and García-González, CA and Otero-Espinar, FJ},
title = {Intravitreal implants manufactured by supercritical foaming for treating retinal diseases.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {362},
number = {},
pages = {342-355},
doi = {10.1016/j.jconrel.2023.08.047},
pmid = {37633363},
issn = {1873-4995},
abstract = {Chronic retinal diseases, such as age-related macular degeneration (AMD), are a major cause of global visual impairment. However, current treatment methods involving repetitive intravitreal injections pose financial and health burdens for patients. The development of controlled drug release systems, particularly for biological drugs, is still an unmet need in prolonging drug release within the vitreous chamber. To address this, green supercritical carbon dioxide (scCO2) foaming technology was employed to manufacture porous poly(lactic-co-glycolic acid) (PLGA)-based intravitreal implants loaded with dexamethasone. The desired implant dimensions were achieved through 3D printing of customised moulds. By varying the depressurisation rates during the foaming process, implants with different porosities and dexamethasone release rates were successfully obtained. These implants demonstrated controlled drug release for up to four months, surpassing the performance of previously developed implants. In view of the positive results obtained, a pilot study was conducted using the monoclonal antibody bevacizumab to explore the feasibility of this technology for preparing intraocular implants loaded with biologic drug molecules. Overall, this study presents a greener and more sustainable alternative to conventional implant manufacturing techniques, particularly suited for drugs that are susceptible to degradation under harsh conditions.},
}
@article {pmid37631061,
year = {2023},
author = {Honisch, C and Rodella, U and Gatto, C and Ruzza, P and Tóthová, JD},
title = {Oxidative Stress and Antioxidant-Based Interventional Medicine in Ophthalmology.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {8},
pages = {},
pmid = {37631061},
issn = {1424-8247},
abstract = {The different anatomical compartments of the eye are highly subjected to reactive oxygen species (ROS) generation due to internal factors, such as metabolic high oxygen consumption, as well as environmental factors, including UV light. An antioxidant defense system is endowed in the eye tissues to regulate ROS quantity and activity. When this homeostatic system is overwhelmed, oxidative stress occurs, causing cellular damage, chronic inflammation, and tissue degeneration. It also plays a significant role in the development and progression of various ocular diseases. Understanding the mechanisms underlying oxidative stress in ocular conditions is thus crucial for the development of effective prevention and treatment strategies. To track marketed products based on antioxidant substances as active ingredients, the databases of the European Medicines Agency and the U.S. Food and Drug Administration were consulted. Only a limited number of items were identified, which were either used as therapeutic treatment or during ocular surgery, including antioxidants, synthetical derivatives, or pro-drugs designed to enhance tissue permeation and activity. This review aims to provide an overview of the primary ocular pathologies associated with oxidative stress and of the available pharmacological interventions centered around antioxidant molecules. Such insights are essential for advancing the development of effective prevention and novel treatment approaches.},
}
@article {pmid37631054,
year = {2023},
author = {Hang, A and Feldman, S and Amin, AP and Ochoa, JAR and Park, SS},
title = {Intravitreal Anti-Vascular Endothelial Growth Factor Therapies for Retinal Disorders.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {8},
pages = {},
pmid = {37631054},
issn = {1424-8247},
support = {n/a//Barbara A. &amp; Alan M. Roth, MD Endowed Chair for Discovery, Education and Patient Care in Vision Science from University of California Davis/ ; },
abstract = {Vascular endothelial growth factors (VEGFs) are key mediator of retinal and choroidal neovascularization as well as retinal vascular leakage leading to macular edema. As such, VEGF plays an important role in mediating visually significant complications associated with common retinal disorders such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Various drugs that inhibit vascular endothelial growth factors (anti-VEGF therapies) have been developed to minimize vision loss associated with these disorders. These drugs are injected into the vitreous cavity in a clinic setting at regular intervals. This article provides an overview of the various anti-VEGF drugs used in ophthalmology and the common retinal conditions that benefit from this therapy.},
}
@article {pmid37629406,
year = {2023},
author = {Fukuda, Y and Notomi, S and Shiose, S and Kano, K and Hashimoto, S and Fujiwara, K and Akiyama, M and Ishikawa, K and Hisatomi, T and Sonoda, KH},
title = {Differences in Central and Peripheral Choroidal Thickness among the Subtypes of Age-Related Macular Degeneration in an Asian Population.},
journal = {Journal of clinical medicine},
volume = {12},
number = {16},
pages = {},
pmid = {37629406},
issn = {2077-0383},
support = {JP21K09702//Japan Society for the Promotion of Science/ ; },
abstract = {Age-related macular degeneration (AMD) causes visual impairment in individuals who are >50 years of age. However, no study has investigated AMD when using ultra-wide-field swept-source optical coherence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thicknesses using UWF SS-OCT, and to compare these across the AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare choroidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9-18 mm from the fovea. PNV patients were significantly younger than those with tAMD (p = 0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (p < 0.01), and choroidal thickness significantly correlated with age and axial length in all subfields (p < 0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.05). In addition, the ratio of the posterior <9 mm to a peripheral 9-18 mm choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.},
}
@article {pmid37629352,
year = {2023},
author = {Tsujinaka, H and Saeki, K and Obayashi, K and Nishi, T and Ueda, T and Ogata, N},
title = {Positive Association between Macular Pigment Optical Density and Glomerular Filtration Rate: A Cross-Sectional Study.},
journal = {Journal of clinical medicine},
volume = {12},
number = {16},
pages = {},
pmid = {37629352},
issn = {2077-0383},
abstract = {Although decreased macular pigment density is associated with the development of age-related macular degeneration (AMD), exactly how this decrease may contribute to the development of AMD is still not fully understood. In this study, we investigated the relationship between macular pigment optical density (MPOD) and estimated glomerular filtration rate (eGFR). MPOD was measured using MPS II (Electron Technology, Cambridge, UK) in 137 participants who showed no clinical signs of AMD at 3 months after cataract surgery, and simple and multiple linear regression analyses were performed to determine the associations with age, sex, abdominal circumference, diabetes, hypertension, smoking, intraocular lens color, visual acuity before and after surgery, and eGFR. The participants were divided into two groups based on the median MPOD (0.58): the high-pigment and low-pigment groups. The mean value of eGFR in the high-pigment group was significantly higher than that in the low-pigment group (64.2 vs. 58.1, p = 0.02). The simple linear regression analysis revealed a significant positive association between MPOD and eGFR (β = 0.0034, 95% confidence interval [CI]: 0.0011-0.0056, p = 0.0038), and this association was independent of age, sex, abdominal circumference, diabetes, smoking, hypertension, best-corrected visual acuity (BCVA) before surgery, BCVA after surgery, and intraocular lens color (β = 0.0033, 95% CI: 0.00090-0.0058, p = 0.0076). These results show a strong association of renal dysfunction with the decrease in MPOD.},
}
@article {pmid37629185,
year = {2023},
author = {Moon, BH and Kim, Y and Kim, SY},
title = {Twenty Years of Anti-Vascular Endothelial Growth Factor Therapeutics in Neovascular Age-Related Macular Degeneration Treatment.},
journal = {International journal of molecular sciences},
volume = {24},
number = {16},
pages = {},
pmid = {37629185},
issn = {1422-0067},
mesh = {Humans ; Aged ; Vascular Endothelial Growth Factors ; Bevacizumab ; *Blindness ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; *Macular Degeneration/drug therapy ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is the primary disastrous retinal disease that leads to blindness in the elderly population. In the early 2000s, nAMD resulted in irreversible vision loss and blindness with no available treatment options. However, there have been breakthrough advances in the drug development of anti-angiogenic biological agents over the last two decades. The primary target molecule for treating nAMD is the vascular endothelial growth factor (VEGF), and there are currently several anti-VEGF drugs such as bevacizumab, ranibizumab, and aflibercept, which have made nAMD more manageable than before, thus preventing vision loss. Nevertheless, it should be noted that these anti-VEGF drugs for nAMD treatment are not effective in more than half of the patients, and even those who initially gain visual improvements lose their vision over time, along with potential deterioration in the geography of atrophy. As a result, there have been continuous endeavors to improve anti-VEGF agents through better efficacy, fewer doses, expanded intervals, and additional targets. This review describes past and current anti-VEGF therapeutics used to treat nAMD and outlines future directions to improve the effectiveness and safety of anti-VEGF agents.},
}
@article {pmid37629157,
year = {2023},
author = {Tsung, TH and Tsai, YC and Lee, HP and Chen, YH and Lu, DW},
title = {Biodegradable Polymer-Based Drug-Delivery Systems for Ocular Diseases.},
journal = {International journal of molecular sciences},
volume = {24},
number = {16},
pages = {},
pmid = {37629157},
issn = {1422-0067},
support = {TSGH-E-112243//Tri-Service General Hospital/ ; MND-MAB-112-153//National Defense Medical Center/ ; },
mesh = {Humans ; *Eye ; Face ; Drug Delivery Systems ; *Glaucoma ; Polymers ; },
abstract = {Ocular drug delivery is a challenging field due to the unique anatomical and physiological barriers of the eye. Biodegradable polymers have emerged as promising tools for efficient and controlled drug delivery in ocular diseases. This review provides an overview of biodegradable polymer-based drug-delivery systems for ocular diseases with emphasis on the potential for biodegradable polymers to overcome the limitations of conventional methods, allowing for sustained drug release, improved bioavailability, and targeted therapy. Natural and synthetic polymers are both discussed, highlighting their biodegradability and biocompatibility. Various formulation strategies, such as nanoparticles, hydrogels, and microemulsions, among others, are investigated, detailing preparation methods, drug encapsulation, and clinical applications. The focus is on anterior and posterior segment drug delivery, covering glaucoma, corneal disorders, ocular inflammation, retinal diseases, age-related macular degeneration, and diabetic retinopathy. Safety considerations, such as biocompatibility evaluations, in vivo toxicity studies, and clinical safety, are addressed. Future perspectives encompass advancements, regulatory considerations, and clinical translation challenges. In conclusion, biodegradable polymers offer potential for efficient and targeted ocular drug delivery, improving therapeutic outcomes while reducing side effects. Further research is needed to optimize formulation strategies and address regulatory requirements for successful clinical implementation.},
}
@article {pmid37629070,
year = {2023},
author = {Liang, H and Wu, Q and Guo, XV and Chan, L and Mao, T and Stella, C and Guilbaud, A and Camperi, J},
title = {Comprehensive Analysis of Photoreceptor Outer Segments: Flow Cytometry Characterization and Stress-Driven Impact on Retinal Pigment Epithelium Phagocytosis.},
journal = {International journal of molecular sciences},
volume = {24},
number = {16},
pages = {},
pmid = {37629070},
issn = {1422-0067},
mesh = {Animals ; Cattle ; *Retinal Pigment Epithelium ; Flow Cytometry ; Neurites ; Neurons ; Phagocytosis ; *Macular Degeneration ; },
abstract = {Phagocytosis is one of the key functions of retinal pigment epithelium (RPE) cells, which maintain photoreceptor health by removing photoreceptor outer segments (POSs) that are regularly shed. A deficiency in RPE function to phagocytose POSs may lead to vision loss in inherited retinal diseases and eventually to age-related macular degeneration (AMD) with geographic atrophy. Significant progress has been made in the field of cell replacement therapy for AMD using stem-cell-derived RPE. To test their function, RPE cells are incubated with purified bovine POSs for the demonstration of efficient binding, internalization, and digestion of POSs. Here, we present an image-based method to measure phagocytosis activity by using POSs labeled with a pH-sensitive fluorescent dye, which has low fluorescence at neutral pH outside of the cell and high fluorescence at low pH inside the phagosome. Further, we introduce a unique flow-cytometry-based method for the characterization of POSs by measuring specific markers for POSs such as rhodopsin and opsin. Using this method, we demonstrated a comparable quality of several bovine POS isolation batches and a reliable assessment of POS quality on RPE phagocytosis assay performance when subjected to different stress conditions. This work provides new tools to characterize POSs and insight into RPE phagocytosis assay development for the functional evaluation of RPE cells in the field of cell replacement therapy.},
}
@article {pmid37627535,
year = {2023},
author = {Velazquez-Soto, H and Groman-Lupa, S and Cruz-Aguilar, M and Salazar, AL and Zenteno, JC and Jimenez-Martinez, MC},
title = {Exogenous CFH Modulates Levels of Pro-Inflammatory Mediators to Prevent Oxidative Damage of Retinal Pigment Epithelial Cells with the At-Risk CFH Y402H Variant.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {8},
pages = {},
pmid = {37627535},
issn = {2076-3921},
support = {NA//Fundaci&#xf3;n Conde de Valenciana/ ; NA//Departamento de Bioqu&#xed;mica, UNAM/ ; },
abstract = {Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and oxidative stress have been implicated in AMD pathogenesis. Oxidative stress causes RPE injury, resulting in a chronic inflammatory response and cell death. The Y402H polymorphism in the complement factor H (CFH) protein is an important risk factor for AMD. However, the functional significance of CFH Y402H polymorphism remains unclear. In the present study, we investigated the role of CFH in the pro-inflammatory response using an in vitro model of oxidative stress in the RPE with the at-risk CFH Y402H variant. ARPE-19 cells with the at-risk CFH Y402H variant were highly susceptible to damage caused by oxidative stress, with increased levels of inflammatory mediators and pro-apoptotic factors that lead to cell death. Pretreatment of the ARPE-19 cell cultures with exogenous CFH prior to the induction of oxidative stress prevented damage and cell death. This protective effect may be related to the negative regulation of pro-inflammatory cytokines. CFH contributes to cell homeostasis and is required to modulate the pro-inflammatory cytokine response under oxidative stress in the ARPE-19 cells with the at-risk CFH Y402H variant.},
}
@article {pmid37626902,
year = {2023},
author = {Borchert, GA and Shamsnajafabadi, H and Hu, ML and De Silva, SR and Downes, SM and MacLaren, RE and Xue, K and Cehajic-Kapetanovic, J},
title = {The Role of Inflammation in Age-Related Macular Degeneration-Therapeutic Landscapes in Geographic Atrophy.},
journal = {Cells},
volume = {12},
number = {16},
pages = {},
pmid = {37626902},
issn = {2073-4409},
support = {/WT_/Wellcome Trust/United Kingdom ; MR/V029762/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; },
mesh = {Humans ; Middle Aged ; *Geographic Atrophy/therapy ; Angiogenesis Inhibitors ; *Wet Macular Degeneration ; Vascular Endothelial Growth Factor A ; Visual Acuity ; Inflammation ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss and visual impairment in people over 50 years of age. In the current therapeutic landscape, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have been central to the management of neovascular AMD (also known as wet AMD), whereas treatments for geographic atrophy have lagged behind. Several therapeutic approaches are being developed for geographic atrophy with the goal of either slowing down disease progression or reversing sight loss. Such strategies target the inflammatory pathways, complement cascade, visual cycle or neuroprotective mechanisms to slow down the degeneration. In addition, retinal implants have been tried for vision restoration and stem cell therapies for potentially a dual purpose of slowing down the degeneration and restoring visual function. In particular, therapies focusing on the complement pathway have shown promising results with the FDA approved pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol, a complement C5 inhibitor. In this review, we discuss the mechanisms of inflammation in AMD and outline the therapeutic landscapes of atrophy AMD. Improved understanding of the various pathway components and their interplay in this complex neuroinflammatory degeneration will guide the development of current and future therapeutic options, such as optogenetic therapy.},
}
@article {pmid37624605,
year = {2023},
author = {Anders, P and Traber, GL and Pfau, M and Riedl, S and Hagag, AM and Camenzind, H and Mai, J and Kaye, R and Bogunovic, H and Fritsche, LG and Rueckert, D and Schmidt-Erfurth, U and Sivaprasad, S and Lotery, AJ and Scholl, HPN},
title = {Comparison of Novel Volumetric Microperimetry Metrics in Intermediate Age-Related Macular Degeneration: PINNACLE Study Report 3.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {8},
pages = {21},
pmid = {37624605},
issn = {2164-2591},
support = {210572/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; *Benchmarking ; Cross-Sectional Studies ; Prospective Studies ; Visual Field Tests ; *Macular Degeneration/diagnosis ; Retina/diagnostic imaging ; },
abstract = {PURPOSE: To investigate and compare novel volumetric microperimetry (MP)-derived metrics in intermediate age-related macular degeneration (iAMD), as current MP metrics show high variability and low sensitivity.<br><br>METHODS: This is a cross-sectional analysis of microperimetry baseline data from the multicenter, prospective PINNACLE study (ClinicalTrials.gov NCT04269304). The Visual Field Modeling and Analysis (VFMA) software and an open-source implementation (OSI) were applied to calculate MP-derived hill-of-vison (HOV) surface plots and the total volume (VTOT) beneath the plots. Bland-Altman plots were used for methodologic comparison, and the association of retinal sensitivity metrics with explanatory variables was tested with mixed-effects models.<br><br>RESULTS: In total, 247 eyes of 189 participants (75 &#xb1; 7.3 years) were included in the analysis. The VTOT output of VFMA and OSI exhibited a significant difference (P < 0.0001). VFMA yielded slightly higher coefficients of determination than OSI and mean sensitivity (MS) in univariable and multivariable modeling, for example, in association with low-luminance visual acuity (LLVA) (marginal R2/conditional R2: VFMA 0.171/0.771, OSI 0.162/0.765, MS 0.133/0.755). In the multivariable analysis, LLVA was the only demonstrable predictor of VFMA VTOT (t-value, P-value: -7.5, <0.001) and MS (-6.5, <0.001).<br><br>CONCLUSIONS: The HOV-derived metric of VTOT exhibits favorable characteristics compared to MS in evaluating retinal sensitivity. The output of VFMA and OSI is not exactly interchangeable in this cross-sectional analysis. Longitudinal analysis is necessary to assess their performance in ability-to-detect change.<br><br>TRANSLATIONAL RELEVANCE: This study explores new volumetric MP endpoints for future application in therapeutic trials in iAMD and reports specific characteristics of the available HOV software applications.},
}
@article {pmid37624109,
year = {2023},
author = {Di Pippo, M and Santia, C and Rullo, D and Ciancimino, C and Grassi, F and Abdolrahimzadeh, S},
title = {The Choroidal Vascularity Index Versus Optical Coherence Tomography Angiography in the Evaluation of the Choroid with a Focus on Age-Related Macular Degeneration.},
journal = {Tomography (Ann Arbor, Mich.)},
volume = {9},
number = {4},
pages = {1456-1470},
pmid = {37624109},
issn = {2379-139X},
mesh = {Humans ; *Tomography, Optical Coherence ; *Macular Degeneration/diagnostic imaging ; Choroid/diagnostic imaging ; Angiography ; Neovascularization, Pathologic ; },
abstract = {The choroid is the most vascularized structure of the eye and it is fundamental for the trophism of the outer retina. Its proper functioning and homeostasis represent key points in maintaining normal retinal physiology. Choroidal alterations may be implicated in the development and progression of numerous pathologies; therefore, in-depth studies using imaging techniques can be of crucial relevance to understanding the pathophysiology of retinal-choroidal diseases. The advent of spectral-domain optical coherence tomography (SDOCT) has enabled the non-invasive study of the choroid in vivo and the most recent development, optical coherence tomography angiography (OCTA), allows for the high-resolution visualization of the choriocapillaris and the choroid in regard to vascularization. The choroidal vascularity index (CVI) is a new parameter calculated on SDOCT scans and is defined as the ratio of the luminal area to the total choroidal area. In this review, a study of the choroid using OCTA and CVI will be evaluated in depth and the pros and cons of these two methods will be analyzed, with a particular focus on age-related macular degeneration.},
}
@article {pmid37622058,
year = {2023},
author = {Popescu, SI and Munteanu, M and Patoni, C and Musat, AMA and Dragoescu, V and Cernat, CC and Popescu, MN and Musat, O},
title = {Role of the Vitreous in Retinal Pathology: A Narrative Review.},
journal = {Cureus},
volume = {15},
number = {8},
pages = {e43990},
pmid = {37622058},
issn = {2168-8184},
abstract = {The vitreous body is an anatomically and biochemically complex structure. Because of its proximity and firm adherence to the retina, researchers have examined the link between these two structures and how their individual pathologies might be connected. Several experimental and clinical studies have already demonstrated the important role of vitreous in the pathogenesis of retinal disorders. This narrative review highlights the role of the vitreous in retinal diseases and the improvements that have been made since the introduction of optical coherence tomography. This leads to a better understanding of vitreoretinal diseases and demonstrates its determinant role in other retinal pathologies, such as diabetic retinopathy or age-related macular degeneration. As we deepen our knowledge of the vitreous's structure, function, and abnormal conditions, we can better link the changes in diseases and identify effective treatments.},
}
@article {pmid37621873,
year = {2023},
author = {Fu, X and Tan, H and Huang, L and Chen, W and Ren, X and Chen, D},
title = {Gut microbiota and eye diseases: a bibliometric study and visualization analysis.},
journal = {Frontiers in cellular and infection microbiology},
volume = {13},
number = {},
pages = {1225859},
pmid = {37621873},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Graves Ophthalmopathy ; *Diabetic Retinopathy ; Dysbiosis ; Inflammation ; Bibliometrics ; *Macular Degeneration ; },
abstract = {INTRODUCTION: Recently the role of gut microbial dysbiosis in many ocular disorders, including but not limited to uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), dry eye, keratitis and orbitopathy is a hot research topic in the field. Targeting gut microbiota to treat these diseases has become an unstoppable trend. Bibliometric study and visualization analysis have become essential methods for literature analysis in the medical research field. We aim to depict this area's research hotspots and future directions by bibliometric software and methods.<br><br>METHODS: We search all the related publications from the Web of Science Core Collection. Then, CiteSpace was applied to analyze and visualize the country distributions, dual-map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to identify authors, co-cited authors, journals and co-cited journals and display the keyword co-occurrence networks.<br><br>RESULTS: A total of 284 relevant publications were identified from 2009 to 2023. The number of studies has been small in the first five years and has grown steadily since 2016. These studies were completed by 1,376 authors from 41 countries worldwide, with the United States in the lead. Lin P has published the most papers while Horai R is the most co-cited author. The top journal and co-cited journal are both Investigative Ophthalmology &amp; Visual Science. In the keyword co-occurrence network, except gut microbiota, inflammation becomes the keyword with the highest frequency. Co-citation analyses reveal that gut dysbiosis is involved in common immune- and inflammation-mediated eye diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, dry eye, and Graves' orbitopathy, and the study of microbiomes is no longer limited to the bacterial populations. Therapeutic strategies that target the gut microbiota, such as probiotics, healthy diet patterns, and fecal microbial transplantation, are effective and critical to future research.<br><br>CONCLUSIONS: In conclusion, the bibliometric analysis displays the research hotspots and developmental directions of the involvement of gut microbiota in the pathogenesis and treatment of some ocular diseases. It provides an overview of this field's dynamic evolution and structural relationships.},
}
@article {pmid37621118,
year = {2024},
author = {Garza-Garza, LA and Villarreal-Martinez, P and Villafuerte-de la Cruz, R and Garza-Leon, M},
title = {Multimodal and longitudinal evaluation of novel phenotype-genotype correlation of CLN3 isolated retinal degeneration in an hispanic female with heterozygous mutations c.944dup and c.1305C&gt;G.},
journal = {Ophthalmic genetics},
volume = {45},
number = {2},
pages = {180-185},
doi = {10.1080/13816810.2023.2245460},
pmid = {37621118},
issn = {1744-5094},
mesh = {Female ; Humans ; Electroretinography ; Fluorescein Angiography ; Heterozygote ; Hispanic or Latino/genetics ; Membrane Glycoproteins/genetics ; Molecular Chaperones/genetics ; Mutation ; Phenotype ; Prospective Studies ; *Retinal Degeneration/diagnosis/genetics ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: Inherited retinal disorders (IRDs) are a complex group of heritable diseases which are characterized by rod, cone, retinal pigment epithelium, or optic nerve dysfunction. Recently, mutations in CLN3 have also been associated with isolated IRDs. Herein, a case with heterozygous CLN3 variations that had not been previously linked to a CLN3-isolated retinal degeneration (CLN3IRD) phenotype in a Hispanic female and its multimodal imaging findings across a 10-year follow-up are presented.<br><br>MATERIAL AND METHODS: An observational, prospective, case report on a hispanic female with CLN3IRD is presented. Patients underwent genetic testing and color fundus photography (CFC) and autofluorescence (FAF), fluorescein angiography (FA), Spectral domain optical coherence tomography (OCT) of the macular area, electroretinogram (ERG) and 30-2 visual field examination through automated perimetry.<br><br>RESULTS: A female, aged 24, affected by CLN3IRD phenotype from c.944dup and c.1305C>G compound heterozygous variants, presented with bilateral hypopigmentary changes in the macular area of OU with that corresponded to hyporautofluorescent deposits in the macular area on FAF. An atrophic maculopathy was evident on structural OCT, and FA disclosed a symmetrical macular hyperflourescence with staining in the early and late stages in OU. Humphrey visual field testing showed a marked reduction of the central visual field in OU. Electrophysiological testing revealed an ERG with markedly decreased a and b waves in OU. In ten years follow up developed of bone spiculae in the midperipheral retina.<br><br>CONCLUSIONS: We reported a patient with a novel CLN3IRD severe phenotype associated with the variants c.944dup and c.1305C>G, which had previously only been associated with JCNL.},
}
@article {pmid37611749,
year = {2024},
author = {Pradhan, S and Sah, RK and Bhandari, G and Bhandari, S and Byanju, R and Kandel, RP and Thompson, IJB and Stevens, VM and Aromin, KM and Oatts, JT and Ou, Y and Lietman, TM and O'Brien, KS and Keenan, JD},
title = {Anterior Segment OCT for Detection of Narrow Angles: A Community-Based Diagnostic Accuracy Study.},
journal = {Ophthalmology. Glaucoma},
volume = {7},
number = {2},
pages = {148-156},
pmid = {37611749},
issn = {2589-4196},
support = {UG1 EY028097/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; *Glaucoma, Angle-Closure/diagnosis ; Trabecular Meshwork ; Sensitivity and Specificity ; *Glaucoma/diagnosis ; },
abstract = {PURPOSE: To assess the diagnostic accuracy of anterior segment OCT (AS-OCT) screening for detecting gonioscopically narrow angles.<br><br>DESIGN: Population-based cross-sectional study.<br><br>PARTICIPANTS: A stratified random sample of individuals aged &#x2265; 60 years, selected from a door-to-door census performed in low-lying Nepal.<br><br>TESTING: Participants underwent AS-OCT, posterior segment OCT, and intraocular pressure (IOP) testing in the community. Those meeting referral criteria in either eye were invited to have a comprehensive eye examination&#xa0;including gonioscopy. Referral criteria included (i) the lowest 2.5% of AS-OCT measurements, (ii) retinal OCT results suggestive of glaucomatous optic neuropathy, diabetic retinopathy, or age-related macular degeneration, and (iii) elevated IOP.<br><br>MAIN OUTCOME MEASURES: Sensitivity and specificity of 5 semiautomated AS-OCT parameters relative to gonioscopically narrow angles, defined as the absence of visible trabecular meshwork for &#x2265; 180&#xb0; on nonindentation&#xa0;gonioscopy.<br><br>RESULTS: Of 17 656 people aged &#x2265; 60 years enumerated from 102 communities, 12 633 (71.6%) presented for AS-OCT testing. Referral was recommended for 697 participants based on AS-OCT criteria and 2419 participants&#xa0;based on other criteria, of which 858 had gonioscopy performed by a glaucoma specialist. Each of the 5 AS-OCT parameters offered good diagnostic information for predicting eyes with gonioscopically narrow angles, with areas under the receiver operating characteristic curve ranging from 0.85 to 0.89. The angle opening distance at 750 &#x3bc;m from the scleral spur (AOD750) provided the most diagnostic information, providing an optimal sensitivity of 87% (95% confidence interval [CI], 75%-96%) and specificity of 77% (71%-83%) at a cutpoint of 367 &#x3bc;m, and a sensitivity of 65% (95% CI, 54%-74%) when specificity was constrained to 90% (cutpoint,&#xa0;283&#xa0;&#x3bc;m).<br><br>CONCLUSIONS: On AS-OCT, the AOD750 parameter detected approximately two-thirds of cases of gonioscopically narrow angles when test specificity was set to 90%. Although such a sensitivity may not be sufficient when screening solely for narrow angles, AS-OCT requires little additional effort if posterior segment OCT is already being performed and thus could provide incremental benefit when performing OCT-based screening.<br><br>FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid37610047,
year = {2023},
author = {Bhattacharya, S and Yin, J and Huo, W and Chaum, E},
title = {Loss of Prom1 impairs autophagy and promotes epithelial-mesenchymal transition in mouse retinal pigment epithelial cells.},
journal = {Journal of cellular physiology},
volume = {238},
number = {10},
pages = {2373-2389},
doi = {10.1002/jcp.31094},
pmid = {37610047},
issn = {1097-4652},
support = {//Research to Prevent Blindness/ ; //NEI core grant P30-EY008126/ ; //Potocsnak family/ ; //Shulsky Foundation/ ; //International Retinal Research Foundation/ ; //Margy Ann and J Donald M Gass Chair endowment/ ; },
abstract = {Mutations in the Prominin-1 (Prom1) gene disrupt photoreceptor disk morphogenesis, leading to macular dystrophies. We have shown that human retinal pigment epithelial (RPE) homeostasis is under the control of Prom1-dependent autophagy, demonstrating that Prom1 plays different roles in the photoreceptors and RPE. It is unclear if retinal and macular degeneration caused by the loss of Prom1 function is a cell-autonomous feature of the RPE or a generalized disease of photoreceptor degeneration. In this study, we investigated whether Prom1 is required for mouse RPE (mRPE) autophagy and phagocytosis, which are cellular processes essential for photoreceptor survival. We found that Prom1-KO decreases autophagy flux, activates mTORC1, and concomitantly decreases transcription factor EB (TFEB) and Cathepsin-D activities in mRPE cells. In addition, Prom1-KO reduces the clearance of bovine photoreceptor outer segments in mRPE cells due to increased mTORC1 and reduced TFEB activities. Dysfunction of Prom1-dependent autophagy correlates with both a decrease in ZO-1 and E-cadherin and a concomitant increase in Vimentin, SNAI1, and ZEB1 levels, consistent with induction of epithelial-mesenchymal transition (EMT) in Prom1-KO mRPE cells. Our results demonstrate that Prom1-mTORC1-TFEB signaling is a central driver of cell-autonomous mRPE homeostasis. We show that Prom1-KO in mRPE leads to RPE defects similar to that seen in atrophic age-related macular degeneration and opens new avenues of investigation targeting Prom1 in retinal degenerative diseases.},
}
@article {pmid37609254,
year = {2023},
author = {Ghosh, S and Sharma, R and Bammidi, S and Koontz, V and Nemani, M and Yazdankhah, M and Kedziora, KM and Wallace, CT and Yu-Wei, C and Franks, J and Bose, D and Rajasundaram, D and Hose, S and Sahel, JA and Puertollano, R and Finkel, T and Zigler, JS and Sergeev, Y and Watkins, SC and Goetzman, ES and Flores-Bellver, M and Kaarniranta, K and Sodhi, A and Bharti, K and Handa, JT and Sinha, D},
title = {The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in atrophic AMD.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.08.08.552343},
pmid = {37609254},
issn = {2692-8205},
support = {R01 DK090242/DK/NIDDK NIH HHS/United States ; R01 EY031594/EY/NEI NIH HHS/United States ; R01 HD103602/HD/NICHD NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of geriatric blindness, is a multi-factorial disease with retinal-pigmented epithelial (RPE) cell dysfunction as a central pathogenic driver. With RPE degeneration, lysosomal function is a core process that is disrupted. Transcription factors EB/E3 (TFEB/E3) tightly control lysosomal function; their disruption can cause aging disorders, such as AMD. Here, we show that induced pluripotent stem cells (iPSC)-derived RPE cells with the complement factor H variant [ CFH (Y402H)] have increased AKT2, which impairs TFEB/TFE3 nuclear translocation and lysosomal function. Increased AKT2 can inhibit PGC1α, which downregulates SIRT5, an AKT2 binding partner. SIRT5 and AKT2 co-regulate each other, thereby modulating TFEB-dependent lysosomal function in the RPE. Failure of the AKT2/SIRT5/TFEB pathway in the RPE induced abnormalities in the autophagy-lysosome cellular axis by upregulating secretory autophagy, thereby releasing a plethora of factors that likely contribute to drusen formation, a hallmark of AMD. Finally, overexpressing AKT2 in RPE cells in mice led to an AMD-like phenotype. Thus, targeting the AKT2/SIRT5/TFEB pathway could be a potential therapy for atrophic AMD.},
}
@article {pmid37606820,
year = {2023},
author = {Gomez-Lumbreras, A and Ghule, P and Panchal, R and Giannouchos, T and Lockhart, CM and Brixner, D},
title = {Real-world evidence in the use of Bevacizumab in age-related macular degeneration (ArMD): a scoping review.},
journal = {International ophthalmology},
volume = {43},
number = {12},
pages = {4527-4539},
pmid = {37606820},
issn = {1573-2630},
mesh = {Adult ; Humans ; Adolescent ; Bevacizumab/therapeutic use ; *Biosimilar Pharmaceuticals/therapeutic use ; Angiogenesis Inhibitors ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Antibodies, Monoclonal, Humanized ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Treatment Outcome ; },
abstract = {PURPOSE: Pharmacological treatments for age-related macular degeneration (ArMD) include anti-vascular endothelial growth factor therapies. Bevacizumab is used off-label, as it has no indication for ArMD. This study aims to identify and describe literature on real-world evidence of bevacizumab (originator or biosimilars) use in ArMD.<br><br>METHODS: A scoping review was conducted in Medline, CINAHL and Embase databases. Studies published in English after September 2017, conducted in USA, including adults (&#x2265;&#x2009;18&#xa0;years old) with ArMD who received treatment with bevacizumab for ArMD were included. The review was further limited to peer-reviewed observational studies that quantitatively analyze either clinical or patient-reported outcomes among patients treated with bevacizumab for ArMD.<br><br>RESULTS: The search strategy retrieved 543 studies. After title and abstract screening, a total of 142 studies were selected for full-text review leading to a total of 12 studies qualifying for data charting. All were retrospective studies. Five (41.6%) of the studies had less than 500 eyes included in the analysis, and the rest had over a thousand eyes. All except one study reported clinical outcomes (visual acuity was the main outcome in 8 (66.6%) studies). There were 3 (25%) studies reporting adverse events of bevacizumab intravitreal injections. None of the studies specified using biosimilars for bevacizumab and none mentioned patient-reported outcomes.<br><br>CONCLUSION: The lack of studies aiming to study the patient-reported outcomes as well as the use of&#xa0;biosimilars of bevacizumab in ArMD makes this field a potential for future research. The different exposures and times to follow-up make it difficult to compare results among the selected studies.},
}
@article {pmid37604141,
year = {2023},
author = {Wu, J and Jiang, Y and Sun, J and Sun, X},
title = {Identification and Validation of an Aging-Associated circRNA-miRNA-mRNA Network in Neovascular Age-Related Macular Degeneration.},
journal = {Gerontology},
volume = {69},
number = {10},
pages = {1218-1231},
pmid = {37604141},
issn = {1423-0003},
mesh = {Humans ; Aged ; *MicroRNAs/genetics ; RNA, Circular/genetics ; RNA, Messenger/genetics/metabolism ; Gene Regulatory Networks ; Gene Expression Profiling ; },
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (NVAMD) is a leading cause of severe vision impairment in the elderly. Aging is one of the most pivotal underlying molecular mechanisms of NVAMD.<br><br>METHODS: In this study, we identified the potential aging-related genes involved in NVAMD. Considering that noncoding RNAs are vital regulators of NVAMD progression, we further explored and constructed an aging-originated circRNA-miRNA-mRNA network of NVAMD. Differential expression of 23 aging-associated genes was identified based on sequencing data and the Human Aging Genomic Resources tool at a threshold of p < 0.05, and log2|fold change| > 1.<br><br>RESULTS: We screened 12 microRNAs (miRNAs) using public datasets and miRNet database. A total of 13 circRNAs were subsequently mined using the starBase tool. Merging these 13 circRNAs, 12 miRNAs, and 15 genes together, we obtained 281 pairs of circRNA-miRNA and 30 pairs of miRNA-mRNA.<br><br>CONCLUSION: We created an aging-related circRNA-miRNA-mRNA network, which could be a promising target for future AMD treatments.},
}
@article {pmid37604084,
year = {2023},
author = {Scalais, E and Geron, C and Pierron, C and Cardillo, S and Schlesser, V and Mataigne, F and Borde, P and Regal, L},
title = {Would, early, versus late hydroxocobalamin dose intensification treatment, prevent cognitive decline, macular degeneration and ocular disease, in 5 patients with early-onset cblC deficiency?.},
journal = {Molecular genetics and metabolism},
volume = {140},
number = {3},
pages = {107681},
doi = {10.1016/j.ymgme.2023.107681},
pmid = {37604084},
issn = {1096-7206},
mesh = {Child, Preschool ; Humans ; Infant ; Male ; *Cognitive Dysfunction/drug therapy ; *Homocystinuria/drug therapy/genetics ; Hydroxocobalamin/therapeutic use ; *Macular Degeneration/drug therapy ; Mammals ; Oxidoreductases ; Vitamin B 12/metabolism ; *Vitamin B 12 Deficiency/drug therapy ; },
abstract = {In early-onset (EO) cblC deficiency (MMACHC), hydroxocobalamin dose-intensification (OHCBL-DI) improved biochemical and clinical outcome. In mammals, Cobalamin is reduced, in a reaction mediated by MMACHC. Pathogenic variants in MMACHC disrupt the synthesis pathway of methyl-cobalamin (MetCbl) and 5'-deoxy-adenosyl-cobalamin (AdoCbl), cofactors for both methionine synthase (MS) and methyl-malonyl-CoA mutase (MCM) enzymes. In 5 patients (pts.), with EO cblC deficiency, biochemical and clinical responses were studied following OHCbl-DI (mean ± SD 6,5 ± 3,3 mg/kg/day), given early, before age 5 months (pts. 1, 2, 3 and 4) or lately, at age 5 years (pt. 5). In all pts., total homocysteine (tHcy), methyl-malonic acid (MMA) and Cob(III)alamin levels were measured. Follow-up was performed during 7[4/12] years (pts. 1, 2, 3), 3[3/12] years (pt. 4) and 3[4/12] years (pt. 5). OHCbl was delivered intravenously or subcutaneously. Mean ± SD serum Cob(III)alamin levels were 42,2 × 10[6] ± 28, 0 × 10[6] pg/ml (normal: 200-900 pg/ml). In all pts., biomarkers were well controlled. All pts., except pt. 5, who had poor vision, had central vision, mild to moderate nystagmus, and with peri-foveolar irregularity in pts. 1, 2 and 4, yet none had the classic bulls' eye maculopathy and retinal degeneration characteristic of pts. with EO cblC deficiency. Only pt. 5, had severe cognitive deficiency. Both visual and cognitive functions were better preserved with early than with late OHCBL-DI. OHCBL-DI is suggested to bypass MMACHC, subsequently to be rescued by methionine synthase reductase (MSR) and adenosyl-transferase (ATR) to obtain Cob(I)alamin resulting in improved cognitive and retinal function in pts. with EO cblC deficiency.},
}
@article {pmid37603784,
year = {2023},
author = {Chiang, T and Kurup, SK and Hariprasad, SM},
title = {Immunological and Inflammatory Side Effects of Treatments for Age-Related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {8},
pages = {440-445},
doi = {10.3928/23258160-20230724-01},
pmid = {37603784},
issn = {2325-8179},
mesh = {Humans ; *Iatrogenic Disease ; *Macular Degeneration ; },
}
@article {pmid37603087,
year = {2024},
author = {Hussain, ZS and Wu, G and Loya, A and Ding, K and Sambhav, K and Riaz, KM and Shah, VA},
title = {DIAGNOSTIC PATTERNS OF AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {44},
number = {1},
pages = {37-46},
doi = {10.1097/IAE.0000000000003912},
pmid = {37603087},
issn = {1539-2864},
mesh = {Aged ; Humans ; Male ; Female ; United States/epidemiology ; Medicare ; Retrospective Studies ; Comorbidity ; *Hypertension ; *Macular Degeneration/epidemiology ; },
abstract = {PURPOSE: To characterize prevalence estimates by race, age, sex, and comorbidity (diabetes and hypertension) within the Medicare beneficiary demographic.<br><br>METHODS: In this US population-based retrospective cohort analysis, the Vision and Eye Health Surveillance System was analyzed for a 100% sample of Medicare Fee-For-Service beneficiary populations of Asians and non-Hispanic Whites between 2014 and 2018. Exclusionary criteria included beneficiaries younger than 40 years. Prevalence rate ratios, defined as prevalence rate for Asians divided by prevalence rate for non-Hispanic Whites, were calculated using multivariate negative binomial regression or Pearson-scaled Poisson regression, stratified by age, sex, and comorbidity.<br><br>RESULTS: A total of 21,892,200 Medicare beneficiaries fulfilled the inclusionary criteria in 2018. Of the entire cohort, 3.2% of the beneficiaries (N = 714,500) were Asian. For beneficiaries aged 40 to 64 years, Asian male (prevalence rate ratios 1.73, 95% confidence interval 1.64-1.83, P < 0.0001) and female (prevalence rate ratios 1.34, 95% confidence interval 1.28-1.41, P < 0.0001) beneficiaries had an increased prevalence rate of all age-related macular degeneration relative to non-Hispanic Whites. Significant time-wise increases in prevalence rate ratios were observed within several age groups, sexes, and comorbidities (race-time interaction coefficients P < 0.05).<br><br>CONCLUSION: This analysis highlights increased age-related macular degeneration prevalence estimates within the Asian American demographic relative to non-Hispanic Whites. Furthermore, specific Asian subpopulations are experiencing accelerated prevalence rates over time.},
}
@article {pmid37602336,
year = {2023},
author = {Wei, YZ and Huang, H and Zhang, X and Yu, HH and Liu, BY and Diao, YY and Cheng, L and Cheng, H},
title = {Identification of retinal thickness and blood flow in age-related macular degeneration with reticular pseudodrusen.},
journal = {International journal of ophthalmology},
volume = {16},
number = {8},
pages = {1268-1273},
pmid = {37602336},
issn = {2222-3959},
abstract = {AIM: To investigate thickness characteristics and vascular plexuses in retinas with reticular pseudodrusen (RPD) as an early detection strategy for age-related macular degeneration (AMD).<br><br>METHODS: This retrospective study included 24 subjects (33 eyes) with RPD and 25 heathy control subjects (34 eyes). The superficial capillary plexus (SCP) and the deep capillary plexus (DCP) of the retinal posterior poles were investigated with optical coherence tomography angiography (OCTA). Retinal thicknesses and vessel densities were analyzed statistically.<br><br>RESULTS: The general retinal thicknesses of RPD eyes were significantly decreased (95%CI -14.080, -0.655; P=0.032). The vessel densities of DCP in RPD eyes were significantly increased in the global (95%CI 1.067, 7.312; P=0.027), parafoveal (95%CI 0.417, 5.241; P=0.022), and perifoveal (95%CI 0.181, 6.842; P=0.039) quadrants. However, the vessel densities of the SCP were rarely increased in the eyes with RPD.<br><br>CONCLUSION: The thinning of retinas in the RPD group suggests a reduction in the number of cells. Additionally, the increased vessel density of the DCP in retinas with RPD indicates a greater demand for blood supply, possibly due to the hypoxia induced RPD compensation caused by RPD in the outer retina. This study highlights the pathological risks associated with RPD and emphasizes the importance of early intervention to retard the progression of AMD.},
}
@article {pmid37602186,
year = {2023},
author = {Chandran, K and Desai, S and Giridhar, A},
title = {Type-3 macular neovascularization in a case of long-standing macular telangiectasia type-2.},
journal = {Oman journal of ophthalmology},
volume = {16},
number = {2},
pages = {377-381},
pmid = {37602186},
issn = {0974-620X},
abstract = {We report a rare case of type-3 macular neovascularization (MNV) in an established case of macular telangiectasia type-2 (MacTel). A 49-year-old healthy Indian woman was diagnosed with MacTel (Gass and Blodi stage 3 in the right eye [OD] and stage 2 in the left eye [OS]) in our retina clinic in January 2004. She was subsequently seen 10 years later with MacTel progression in OD (stage 4) and drusenoid changes in both eyes. She recently complained of sudden onset diminution of vision in OS of 1 week duration. The best-corrected visual acuity, when she attended this day, was 20/500 (OD) and 20/60 (OS). Fundus revealed pigment deposition in the macula in OD and a large pigment epithelial detachment (PED) in OS with drusen in both eyes, suggesting coexisting age macular degeneration (AMD) and MacTel (stage 4 OD; stage 2 OS) bilaterally. Multimodal imaging with spectral-domain optical coherence tomography showed drusen, a large trapezoid PED with central apical disruption, outer retinal hyperreflective material, intraretinal fluid, and inner retinal cavitation. Indocyanine green angiography revealed "hotspot" at center of the PED with hairpin-loop vessels. Optical coherence tomography angiography demonstrated network at apex of the PED. These features confirmed a diagnosis of type-3 MNV (classical retinal angiomatous proliferation [RAP] lesion) in OS along with features of AMD and MacTel. There was resolution of intraretinal fluid and reduction in height of PED following three loading doses of intravitreal ranibizumab in OS. Although type-3 neovascularization has been described in MacTel, to the best of our knowledge, this is the first documentation of classical RAP features of MNV with all described multimodal imaging features. The type-3 neovascularization typically described in association with MacTel is retinal-retinal, retinal-subretinal, and retinochoroidal anastomosis (RCA). Although RAP is also associated with RCA, the features seen in our case, i.e., triad of erosion at the roof of PED, inverted flap in the PED, and hotspot in the center of PED, have not been documented in association with MacTel.},
}
@article {pmid37600916,
year = {2023},
author = {Moghadam Fard, A and Mirshahi, R and Naseripour, M and Ghasemi Falavarjani, K},
title = {Stem Cell Therapy in Stargardt Disease: A Systematic Review.},
journal = {Journal of ophthalmic &amp; vision research},
volume = {18},
number = {3},
pages = {318-327},
pmid = {37600916},
issn = {2008-2010},
abstract = {This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.},
}
@article {pmid37599800,
year = {2023},
author = {Alsaqr, A and Alharbi, M and Aldossary, N and Alruwished, A and Alharbi, M and Alghaib, K and Alabdulkarim, A and Alhamdan, S and Almutleb, E and Abusharha, A},
title = {Assessment of macular pigment optical density in Arab population and its relationship to people's anthropometric data: a cross-sectional study.},
journal = {Therapeutic advances in ophthalmology},
volume = {15},
number = {},
pages = {25158414231189099},
pmid = {37599800},
issn = {2515-8414},
abstract = {BACKGROUND: Anthropometry facilitates the evaluation of risks associated with reduced macular pigment optical density (MPOD).<br><br>OBJECTIVES: To investigate the predictors and anthropometric indices associated with MPOD in healthy adult in Arab population.<br><br>DESIGN: This is a cross-sectional study.<br><br>METHODS: The MPOD was measured at 0.5&#xb0; from fovea using a heterochromatic flicker photometer. Healthy participants aged between 20 and 40&#x2009;years were recruited. The study evaluated the following data of the participants: height, weight, body mass index, body fat percentage, basal metabolic rate, visceral fat level, muscle mass, bone mineral content, and percentage of protein and body water. The correlation between MPOD with anthropometrics and demographic data was evaluated using Spearman's correlation test. The differences among genders were investigated using the Mann-Whitney U test. The smoking effect on MPOD was analyzed using the Friedman test.<br><br>RESULTS: In all, 143 participants were recruited. The median&#x2009;&#xb1;&#x2009;interquartile range was calculated for age (23&#x2009;&#xb1;&#x2009;4&#x2009;years), visual acuity (0.00&#x2009;&#xb1;&#x2009;0.00&#x2009;logMAR), and MPOD (0.41&#x2009;&#xb1;&#x2009;0.18). The average MPOD was higher in males than in females but it was not statistically significant (p&#x2009;>&#x2009;0.05); on the other hand, they were statistically significantly different in most of the anthropometric data. A significant relationship was found between MPOD and percentage of body fat, protein, and body water (r&#x2009;=&#x2009;0.30, p&#x2009;<&#x2009;0.05). The observed median MPOD value was higher in this study than that found in previous studies in white populations, but lower than that found in studies investigating Asian populations.<br><br>CONCLUSION: One of the most important risk factors of age-related macular degeneration is associated with a relative absence of macular pigment. This study brought into focus percentage of protein and body water for further studies as well as the well-established links with body fat and obesity. Unknown predictors of MPOD remain uncovered. The study also provided first report on normative values of MPOD for Arab population and confirmed the differences from other ethnicities.},
}
@article {pmid37598860,
year = {2024},
author = {Li, CHZ and Pas, JAAH and Corradi, Z and Hitti-Malin, RJ and Hoogstede, A and Runhart, EH and Dhooge, PPA and Collin, RWJ and Cremers, FPM and Hoyng, CB},
title = {Study of Late-Onset Stargardt Type 1 Disease: Characteristics, Genetics, and Progression.},
journal = {Ophthalmology},
volume = {131},
number = {1},
pages = {87-97},
doi = {10.1016/j.ophtha.2023.08.011},
pmid = {37598860},
issn = {1549-4713},
mesh = {Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Stargardt Disease ; Retrospective Studies ; *ATP-Binding Cassette Transporters/genetics ; Electroretinography ; *Retinal Degeneration ; Tomography, Optical Coherence ; Atrophy ; Disease Progression ; Fluorescein Angiography ; },
abstract = {PURPOSE: Late-onset Stargardt disease is a subtype of Stargardt disease type 1 (STGD1), defined by an age of onset of 45 years or older. We describe the disease characteristics, underlying genetics, and disease progression of late-onset STGD1 and highlight the differences from geographic atrophy.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Seventy-one patients with late-onset STGD1.<br><br>METHODS: Medical files were reviewed for clinical data including age at onset, initial symptoms, and best-corrected visual acuity. A quantitative and qualitative assessment of retinal pigment epithelium (RPE) atrophy was performed on fundus autofluorescence images and OCT scans.<br><br>MAIN OUTCOME MEASURES: Age at onset, genotype, visual acuity, atrophy growth rates, and loss of external limiting membrane, ellipsoid zone, and RPE.<br><br>RESULTS: Median age at onset was 55.0 years (range, 45-82 years). A combination of a mild and severe variant in ATP-binding cassette subfamily A member 4 (ABCA4) was the most common genotype (n&#xa0;= 49 [69.0%]). The most frequent allele, c.5603A&#x2192;T (p.Asn1868Ile), was present in 43 of 71 patients (60.6%). No combination of 2 severe variants was found. At first presentation, all patients have flecks. Foveal-sparing atrophy was present in 33.3% of eyes, whereas 21.1% had atrophy with foveal involvement. Extrafoveal atrophy was present in 38.9% of eyes, and no atrophy was evident in 6.7% of eyes. Time-to-event curves showed a median duration of 15.4 years (95% confidence interval, 11.1-19.6 years) from onset to foveal involvement. The median visual acuity decline was -0.03 Snellen decimal per year (interquartile range [IQR], -0.07 to 0.00 Snellen decimal; 0.03 logarithm of the minimum angle of resolution). Median atrophy growth was 0.590 mm[2]/year (IQR, 0.046-1.641 mm[2]/year) for definitely decreased autofluorescence and 0.650 mm[2]/year (IQR, 0.299-1.729 mm[2]/year) for total decreased autofluorescence.<br><br>CONCLUSIONS: Late-onset STGD1 is a subtype of STGD1 with most commonly 1 severe and 1 mild ABCA4 variant. The general patient presents with typical fundus flecks and retinal atrophy in a foveal-sparing pattern with preserved central vision. Misdiagnosis as age-related macular degeneration should be avoided to prevent futile invasive treatments with potential complications. In addition, correct diagnosis lends patients with late-onset STGD1 the opportunity to participate in potentially beneficial therapeutic trials for STGD1.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid37598400,
year = {2023},
author = {Hu, S and Chen, Y and Xie, D and Xu, K and Fu, Y and Chi, W and Liu, H and Huang, J},
title = {Nme2 Cas9-mediated therapeutic editing in inhibiting angiogenesis after wet age-related macular degeneration onset.},
journal = {Clinical and translational medicine},
volume = {13},
number = {8},
pages = {e1383},
pmid = {37598400},
issn = {2001-1326},
mesh = {Aged ; Humans ; *Vascular Endothelial Growth Factor A/genetics ; CRISPR-Cas Systems/genetics ; *Macular Degeneration/genetics/therapy ; Immunotherapy ; Gene Editing ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD), particularly wet AMD characterised by choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. The hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway contributes to CNV pathogenesis. Previous gene editing research indicated that disrupting these genes in retinal pigment epithelial cells could have a preventive effect on CNV progression. However, no studies have yet been conducted using gene editing to disrupt VEGF signalling after CNV induction for therapeutic validation, which is critical to the clinical application of wet AMD gene editing therapies.<br><br>METHOD: Here, we employed the single-adeno-associated virus-mediated Nme2 Cas9 to disrupt key molecules in VEGF signalling, Hif1&#x3b1;, Vegfa and Vegfr2 after inducing CNV and estimated their therapeutic effects.<br><br>RESULTS: We found that Nme2 Cas9 made efficient editing in target genes up to 71.8% post 11 days in vivo. And only Nme2 Cas9-Vegfa treatment during the early stage of CNV development reduced the CNV lesion area by 49.5%, compared to the negative control, while Nme2 Cas9-Hif1&#x3b1; or Nme2 Cas9-Vegfr2 treatment did not show therapeutic effect. Besides, no off-target effects were observed in Nme2 Cas9-mediated gene editing in vivo.<br><br>CONCLUSIONS: This study provides proof-of-concept possibility of employing Nme2 Cas9 for potential anti-angiogenesis therapy in wet AMD.},
}
@article {pmid37598260,
year = {2024},
author = {Yoon, JM and Lim, DH and Lee, YB and Han, K and Kim, BS and Koo, HY and Jung, SY and Shin, DW and Ham, DI},
title = {The risk of fracture in age-related macular degeneration according to the presence of visual disability: a nationwide cohort study.},
journal = {Eye (London, England)},
volume = {38},
number = {2},
pages = {364-371},
pmid = {37598260},
issn = {1476-5454},
support = {2021R1C1C1007795//National Research Foundation of Korea (NRF)/ ; HI20C1073//Korea Health Industry Development Institute (KHIDI)/ ; },
mesh = {Humans ; Cohort Studies ; Risk Factors ; *Macular Degeneration/complications/epidemiology/diagnosis ; Republic of Korea/epidemiology ; Proportional Hazards Models ; },
abstract = {PURPOSE: To evaluate the association between age-related macular degeneration (AMD) with or without visual disability (VD) and the risk of fracture using the National Health Insurance data in South Korea.<br><br>METHODS: In total, 3,894,702 individuals who had taken part in health-screening programs between January 1, 2009, and December 31, 2009, were included in the cohort and followed until December 31, 2019. The participants with VD, which could be related to the severity of AMD, were defined as those with a loss of vision or visual field defect as certified by the Korean government's Ministry of Health and Welfare. The hazard ratio was calculated for groups (control and AMD with/without VD) using the multivariable-adjusted cox regression analysis.<br><br>RESULTS: In total, 466,890 participants (11.99%) were diagnosed with fractures during the study period. An increased risk of fracture was observed in individuals with AMD compared with the control (adjusted hazard ratio (aHR), 1.09, 95% confidence interval (CI), 1.06-1.11). Furthermore, among the AMD individuals, an increased risk of fracture was prominent in individuals with VD (aHR 1.17, 95% CI 1.08-1.27) than those without VD (aHR 1.08, 95% CI 1.06-1.11) compared with the reference group (control).<br><br>CONCLUSIONS: AMD was associated with an increased risk of fracture even without VD. Prevention for fracture should be considered in AMD patients, especially when accompanied by VD.},
}
@article {pmid37598106,
year = {2023},
author = {Benlaribi, M},
title = {[Prechoroidal clefting in age-related macular degeneration with type I choroidal neovascularization].},
journal = {Journal francais d'ophtalmologie},
volume = {46},
number = {8},
pages = {980-982},
doi = {10.1016/j.jfo.2023.06.003},
pmid = {37598106},
issn = {1773-0597},
mesh = {Humans ; *Choroidal Neovascularization/complications/diagnosis ; *Macular Degeneration/complications/diagnosis ; Fluorescein Angiography ; Retrospective Studies ; },
}
@article {pmid37598105,
year = {2023},
author = {Sayin, N and Kocak, I and Pehlivanoğlu, S and Pekel, G and Er, A and Bayramoğlu, SE and Aydin, A},
title = {A quantitative sonoelastography evaluation of ocular and periocular elasticity after intravitreal ranibizumab injection.},
journal = {Journal francais d'ophtalmologie},
volume = {46},
number = {9},
pages = {1030-1038},
doi = {10.1016/j.jfo.2023.03.016},
pmid = {37598105},
issn = {1773-0597},
mesh = {Humans ; *Ranibizumab/administration &amp; dosage ; *Elasticity Imaging Techniques/methods ; Male ; Female ; *Intravitreal Injections ; Aged ; Middle Aged ; *Elasticity/drug effects/physiology ; Aged, 80 and over ; Angiogenesis Inhibitors/administration &amp; dosage ; Eye/drug effects/diagnostic imaging ; },
abstract = {PURPOSE: We evaluated changes in ocular and periocular elasticity by ultrasound (US) elastography in intravitreal ranibizumab-treated eyes and the healthy fellow eyes of patients with neovascular AMD.<br><br>METHODS: The study was performed on 52 eyes of 26 volunteers who ranged in age from 59 to 89 (mean 72&#xb1;7.78) years old. The study group consisted of the patients with neovascular AMD treated with intravitreal ranibizumab. The fellow eyes (without choroidal neovascularization) of the study group were selected as the control group. All patients were examined with sonoelastography before intravitreal injection and at 1day, 1week, and 1month after intravitreal injection. All images were acquired with a Toshiba Aplio 500 ultrasound system (Tokyo, Japan) including software with a combined autocorrelation method and a multifrequency linear probe. The elastography values of the anterior vitreous (AV), posterior vitreous (PV), retina-choroid-sclera complex (RCS), retrobulbar fat tissue (RF), optic nerve head (ONH) and retrobulbar optic nerve (RON) were measured in each eye.<br><br>RESULTS: There were 13 male (50%) and 13 female (50%) participants in our study. Anterior vitreous, posterior vitreous, RCS, retrobulbar fat tissue, ONH, and RON US elastography values were similar in both groups (P&#x2c3;0.05 for all). On the other hand, there was a positive correlation between the difference between baseline and 1-month PV sonoelastography values and age (r=0.47, P=0.035).<br><br>CONCLUSION: A single dose intravitreal Ranibizumab (Lucentis&#xae;, Genentech, USA) injection does not alter the elasticity of ocular and periocular structures.},
}
@article {pmid37595568,
year = {2024},
author = {Lavoie, J and Besrour, M and Lemaire, W and Rouat, J and Fontaine, R and Plourde, E},
title = {Learning to see via epiretinal implant stimulationin silicowith model-based deep reinforcement learning.},
journal = {Biomedical physics &amp; engineering express},
volume = {10},
number = {2},
pages = {},
doi = {10.1088/2057-1976/acf1a5},
pmid = {37595568},
issn = {2057-1976},
mesh = {Humans ; *Prostheses and Implants ; Retina/diagnostic imaging ; Retinal Ganglion Cells/physiology ; *Retinitis Pigmentosa ; Microelectrodes ; },
abstract = {OBJECTIVE: Diseases such as age-related macular degeneration and retinitis pigmentosa cause the degradation of the photoreceptor layer. One approach to restore vision is to electrically stimulate the surviving retinal ganglion cells with a microelectrode array such as epiretinal implants. Epiretinal implants are known to generate visible anisotropic shapes elongated along the axon fascicles of neighboring retinal ganglion cells. Recent work has demonstrated that to obtain isotropic pixel-like shapes, it is possible to map axon fascicles and avoid stimulating them by inactivating electrodes or lowering stimulation current levels. Avoiding axon fascicule stimulation aims to remove brushstroke-like shapes in favor of a more reduced set of pixel-like shapes.<br><br>APPROACH: In this study, we propose the use of isotropic and anisotropic shapes to render intelligible images on the retina of a virtual patient in a reinforcement learning environment named rlretina. The environment formalizes the task as using brushstrokes in a stroke-based rendering task.<br><br>MAIN RESULTS: We train a deep reinforcement learning agent that learns to assemble isotropic and anisotropic shapes to form an image. We investigate which error-based or perception-based metrics are adequate to reward the agent. The agent is trained in a model-based data generation fashion using the psychophysically validated axon map model to render images as perceived by different virtual patients. We show that the agent can generate more intelligible images compared to the naive method in different virtual patients.<br><br>SIGNIFICANCE: This work shares a new way to address epiretinal stimulation that constitutes a first step towards improving visual acuity in artificially-restored vision using anisotropic phosphenes.},
}
@article {pmid37589984,
year = {2023},
author = {Kaufmann, GT and Hyman, MJ and Gonnah, R and Hariprasad, S and Skondra, D},
title = {Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {11},
pages = {22},
pmid = {37589984},
issn = {1552-5783},
mesh = {Humans ; *Diabetic Retinopathy ; Case-Control Studies ; *Geographic Atrophy ; *Macular Degeneration/drug therapy/epidemiology/prevention &amp; control ; *Metformin/therapeutic use ; *Diabetes Mellitus/drug therapy/epidemiology ; },
abstract = {PURPOSE: To investigate if metformin use is associated with decreased odds of developing new non-neovascular ("dry") age-related macular degeneration (AMD).<br><br>METHODS: Case-control study examining 194,135 cases with diagnoses of new-onset AMD between 2008 and 2017 and 193,990 matched controls in the Merative MarketScan Research Databases. The diabetic subgroup included 49,988 cases and 49,460 controls. Multivariable conditional logistic regressions identified the risks of exposures on the development of dry AMD. Main outcome measures were odds ratios (ORs) of developing dry AMD with metformin use.<br><br>RESULTS: In multivariable conditional logistic regression, any metformin use was associated with decreased odds of developing dry AMD (OR = 0.97; 95% confidence interval [CI], 0.95-0.99). This protective effect was noted for cumulative 2-year doses of metformin of 1 to 270 g (OR = 0.93; 95% CI, 0.90-0.97) and 271 to 600 g (OR = 0.92; 95% CI, 0.89-0.96). In a diabetic subgroup, metformin use below 601 g per 2 years decreased the odds of developing dry AMD (1-270 g: OR = 0.95; 95% CI, 0.91-0.99; 271-600 g: OR = 0.92; 95% CI, 0.89-0.96). Unlike in diabetic patients with diabetic retinopathy, diabetic patients without diabetic retinopathy had decreased odds of developing dry AMD with any metformin use (OR = 0.97; 95% CI, 0.94-0.998) and cumulative two-year doses of 1 to 270 g (OR 0.96; 95% CI, 0.91-0.998) and 271 to 600 g (OR = 0.92; 95% CI, 0.88-0.96).<br><br>CONCLUSIONS: Metformin use was associated with decreased odds of developing dry AMD. The protective effect was observed for cumulative 2-year doses below 601 g. In diabetics, this association persisted, specifically in those without diabetic retinopathy. Therefore, metformin may be a strategy to prevent development of dry AMD.},
}
@article {pmid37586867,
year = {2023},
author = {Yiallouridou, C and Acton, JH and Banerjee, S and Waterman, H and Wood, A},
title = {Pain related to intravitreal injections for age-related macular degeneration: a qualitative study of the perspectives of patients and practitioners.},
journal = {BMJ open},
volume = {13},
number = {8},
pages = {e069625},
pmid = {37586867},
issn = {2044-6055},
mesh = {Humans ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Pain/drug therapy/etiology ; Anxiety/etiology ; Emotions ; },
abstract = {OBJECTIVES: Ocular pain is a commonly reported finding in the intravitreal injection procedure, but post-injection experiences and patient adherence to treatment remain underexplored. We therefore aimed to identify key variations in the intravitreal injection procedure that may influence pain, and to gain insights into the post-injection experience and treatment adherence from the perspective of patients and practitioners.<br><br>DESIGN: Qualitative semistructured interview study using reflexive thematic analysis of transcripts.<br><br>SETTING: Hospital Eye Clinic in Wales, UK. Interviews were conducted between May and September 2019.<br><br>PARTICIPANTS: Purposive sample of patients aged &#x2265;50 years with neovascular age-related macular degeneration and no other retinal pathology who had received at least six intravitreal injections, and practitioners including ophthalmologists, registered nurses and optometrists who performed intravitreal injections at the research site.<br><br>RESULTS: Data saturation was reached with 21 interviews: 14 patients and 7 practitioners. Three main themes were identified from the analysis: fear of losing eyesight and treatment anxiety influence patient adherence to treatment, variability in pain experience during treatment, and post-injection experience and impact on patient recovery. To reassure patients feeling apprehensive about the injections, practitioners promoted safety and trust, and used techniques to manage anxiety. Key variations that may influence pain identified were application of antiseptic or anaesthetic, injecting methods and communication. During injection, patients reported a dull-aching and sharp pain, contrary to practitioners' perspective of feeling a 'pressure'. Patients described prolonged soreness and irritation of up to 36 hours post-injection affecting their sleep and recovery.<br><br>CONCLUSION: Establishing rapport supported patients to recognise the necessity of ongoing treatment to prevent sight loss; however, inadequate pain management led to undesirable outcomes. Practitioners should use pain assessment tools during and immediately after injection and provide ongoing consistent information to help patients manage pain at home.},
}
@article {pmid37586826,
year = {2023},
author = {Hujanen, P and Ruha, H and Lehtonen, E and Pirinen, I and Huhtala, H and Vaajanen, A and Syvänen, U and Tuulonen, A and Uusitalo-Järvinen, H},
title = {Ten-year real-world outcomes of antivascular endothelial growth factor therapy in neovascular age-related macular degeneration using pro re nata regimen.},
journal = {BMJ open ophthalmology},
volume = {8},
number = {1},
pages = {},
pmid = {37586826},
issn = {2397-3269},
mesh = {Humans ; Endothelial Growth Factors ; Clinical Protocols ; Bevacizumab/therapeutic use ; *Diabetic Retinopathy ; *Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND/AIMS: To analyse long-term outcomes of antivascular endothelial growth factor (anti-VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD) using pro re nata (PRN) regimen in a single-centre clinical practice.<br><br>METHODS: All patients receiving intravitreal injection (IVI) for nAMD between 1 January 2008 and 31 December 2020 were searched from electronic medical records. All 3844 treatment-na&#xef;ve eyes of 3008 patients were included with a total of 50 146 IVIs (87% bevacizumab) administered. Main outcome measures were mean change in visual acuity (VA) from baseline, proportion of eyes within 15 letters of baseline, proportion of eyes with VA &#x2265;20/40 Snellen and &#x2264;20/200 Snellen, number of annual visits and number of annual IVIs.<br><br>RESULTS: The mean baseline VA was 55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the mean change in VA from baseline was +2, +2, &#xb1;0, -2, -2 and -4 ETDRS letters at year 1, 2, 3, 5, 7 and 10, respectively. Proportions of eyes within 15 letters of baseline were 88%, 87%, 82%, 80%, 76% and 72% at the end of years 1, 2, 3, 5, 7 and 10, respectively. The median number of annual IVI was 6 at years 1-7 and 5 at year 10. The median number of annual total visits was 10 at year 1, 9 at years 2-7 and 8 at year 10, respectively.<br><br>CONCLUSIONS: VA was maintained short-term and long-term with anti-VEGF therapy using PRN treatment regimen.},
}
@article {pmid37586372,
year = {2023},
author = {Tan, LX and Germer, CJ and Thamban, T and La Cunza, N and Lakkaraju, A},
title = {Optineurin tunes outside-in signaling to regulate lysosome biogenesis and phagocytic clearance in the retina.},
journal = {Current biology : CB},
volume = {33},
number = {18},
pages = {3805-3820.e7},
pmid = {37586372},
issn = {1879-0445},
support = {P30 EY002162/EY/NEI NIH HHS/United States ; P30 EY016665/EY/NEI NIH HHS/United States ; R01 EY023299/EY/NEI NIH HHS/United States ; R01 EY030668/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; *Lysosomes/metabolism ; Phagocytosis ; Retinal Pigment Epithelium/metabolism ; TOR Serine-Threonine Kinases/metabolism ; *Macular Degeneration/metabolism ; },
abstract = {Balancing the competing demands of phagolysosomal degradation and autophagy is a significant challenge for phagocytic tissues. Yet how this plasticity is accomplished in health and disease is poorly understood. In the retina, circadian phagocytosis and degradation of photoreceptor outer segments by the postmitotic retinal pigment epithelium (RPE) are essential for healthy vision. Disrupted autophagy due to mechanistic target of rapamycin (mTOR) overactivation in the RPE is associated with blinding macular degenerations; however, outer segment degradation is unaffected in these diseases, indicating that distinct mechanisms regulate these clearance mechanisms. Here, using advanced imaging and mouse models, we identify optineurin as a key regulator that tunes phagocytosis and lysosomal capacity to meet circadian demands and helps prioritize outer segment clearance by the RPE in macular degenerations. High-resolution live-cell imaging implicates optineurin in scissioning outer segment tips prior to engulfment, analogous to microglial trogocytosis of neuronal processes. Optineurin is essential for recruiting light chain 3 (LC3), which anchors outer segment phagosomes to microtubules and facilitates phagosome maturation and fusion with lysosomes. This dynamically activates transcription factor EB (TFEB) to induce lysosome biogenesis in an mTOR-independent, transient receptor potential-mucolipin 1 (TRPML1)-dependent manner. RNA-seq analyses show that expression of TFEB target genes temporally tracks with optineurin recruitment and that lysosomal and autophagy genes are controlled by distinct transcriptional programs in the RPE. The unconventional plasma membrane-to-nucleus signaling mediated by optineurin ensures outer segment degradation under conditions of impaired autophagy in macular degeneration models. Independent regulation of these critical clearance mechanisms would help safeguard the metabolic fitness of the RPE throughout the organismal lifespan.},
}
@article {pmid37585566,
year = {2024},
author = {Vilela, MAP and Arrigo, A and Parodi, MB and da Silva Mengue, C},
title = {Smartphone Eye Examination: Artificial Intelligence and Telemedicine.},
journal = {Telemedicine journal and e-health : the official journal of the American Telemedicine Association},
volume = {30},
number = {2},
pages = {341-353},
doi = {10.1089/tmj.2023.0041},
pmid = {37585566},
issn = {1556-3669},
mesh = {Humans ; *Smartphone ; *Artificial Intelligence ; *Telemedicine ; *Eye Diseases/diagnosis/diagnostic imaging ; Ophthalmoscopy/methods ; },
abstract = {Background: The current medical scenario is closely linked to recent progress in telecommunications, photodocumentation, and artificial intelligence (AI). Smartphone eye examination may represent a promising tool in the technological spectrum, with special interest for primary health care services. Obtaining fundus imaging with this technique has improved and democratized the teaching of fundoscopy, but in particular, it contributes greatly to screening diseases with high rates of blindness. Eye examination using smartphones essentially represents a cheap and safe method, thus contributing to public policies on population screening. This review aims to provide an update on the use of this resource and its future prospects, especially as a screening and ophthalmic diagnostic tool. Methods: In this review, we surveyed major published advances in retinal and anterior segment analysis using AI. We performed an electronic search on the Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, and Cochrane Library for published literature without a deadline. We included studies that compared the diagnostic accuracy of smartphone ophthalmoscopy for detecting prevalent diseases with an accurate or commonly employed reference standard. Results: There are few databases with complete metadata, providing demographic data, and few databases with sufficient images involving current or new therapies. It should be taken into consideration that these are databases containing images captured using different systems and formats, with information often being excluded without essential detailing of the reasons for exclusion, which further distances them from real-life conditions. The safety, portability, low cost, and reproducibility of smartphone eye images are discussed in several studies, with encouraging results. Conclusions: The high level of agreement between conventional and a smartphone method shows a powerful arsenal for screening and early diagnosis of the main causes of blindness, such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration. In addition to streamlining the medical workflow and bringing benefits for public health policies, smartphone eye examination can make safe and quality assessment available to the population.},
}
@article {pmid37585239,
year = {2022},
author = {Vofo, BN and Cnaany, Y and Chowers, I},
title = {Clinical outcome using a modified treat-and-extend protocol for neovascular age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {7},
number = {1},
pages = {},
pmid = {37585239},
issn = {2397-3269},
mesh = {Humans ; *Ranibizumab ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Treatment Outcome ; Intravitreal Injections ; *Macular Degeneration/diagnostic imaging ; },
abstract = {AIM: To compare outcome between patients treated using a modified treat-and-extend (mT&amp;E) protocol and patients treated using a conventional T&amp;E protocol.<br><br>METHODS: A retrospective cohort study of two groups of treatment-na&#xef;ve neovascular age-related macular degeneration patients within a single centre were evaluated. One group treated using the conventional T&amp;E protocol, with visual acuity, dilated fundus examination (DFE) and optical coherence tomography (OCT) performed at each visit. The second group treated using the mT&amp;E protocol in which visual acuity and DFE were performed only every three visits. The main outcome measures were time spent per clinical visit, visual and anatomical outcomes measured for 36 months.<br><br>RESULTS: The T&amp;E and mT&amp;E groups included 135 eyes in 116 patients and 119 eyes in 94 patients, respectively, with similar baseline characteristics. At 36 months, the number of injections administered (7.9&#xb1;2.9 vs 8.1&#xb1;2.3 injections, respectively; p=0.55), the percentage of eyes that gained &#x2265;15 Early Treatment for Diabetic Retinopathy Study (ETDRS) letters (23% vs 25.2%, respectively; p=0.39) and the percentage of eyes that lost &#x2265;15 ETDRS letters (21.5% vs 17.7%; p=0.43, respectively) were similar between the T&amp;E and mT&amp;E groups. However, waiting and contact time were reduced during the OCT-only visits compared with the full visits, with an average of 41 min saved per patient encounter.<br><br>CONCLUSIONS: Both protocols yielded similar visual and anatomical outcomes. However, the mT&amp;E protocol reduced the number of full visits, with considerably less time spent at the clinic.},
}
@article {pmid37583576,
year = {2023},
author = {Chakraborty, D and Thakkar, M and Venkatesh, R and Roy, S and Bhavsar, M and Karcher, H},
title = {Short-Term Treatment Outcomes of Brolucizumab in Patients with Neovascular Age-Related Macular Degeneration: A Multicentre Indian Real-World Evidence Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {2295-2307},
pmid = {37583576},
issn = {1177-5467},
abstract = {OBJECTIVE: To evaluate the short-term effectiveness and safety outcomes following brolucizumab treatment in patients with neovascular age-related macular degeneration (nAMD) as a part of real-world clinical practice in India.<br><br>METHODS: This was a retrospective, observational, multicentre study including patients (&#x2265;50 years old) diagnosed with nAMD. Anonymized data of the patients receiving the first dose of brolucizumab intravitreal injection (IVI) who were either treatment-na&#xef;ve or previously treated with a single or a combination of other anti-VEGF IVIs were included. The present study reported the change in retinal fluid levels from baseline to month 3, best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of injections received. The adverse events in the three months after brolucizumab treatment initiation were also monitored.<br><br>RESULTS: The study included 63 patients (65 eyes) from four study centres across India (mean age: 69.1 &#xb1; 9.7 years). A total of 82 brolucizumab injections were administered during the 3 months of study duration, with 52/65 (80.0%) eyes receiving only 1 injection. Resolution of IRF, SRF, and PED was observed in 76.9%, 64.6%, and 67.7% of eyes, respectively. Further, a significant reduction in CRT was observed (baseline: 403.5 &#xb1; 118.7 &#x3bc;m; month 3: 308.3 &#xb1; 73.8 &#x3bc;m; p < 0.001), and BCVA also improved notably from 0.7 &#xb1; 0.5 logMAR at baseline to 0.5 &#xb1; 0.4 logMAR at month 3 (p < 0.001). Adverse events (AEs) were reported in 3 eyes from 3 patients; retinal pigment epithelial rip (1) and subretinal hemorrhage (2) after the first injection of brolucizumab, however, none discontinued the treatment.<br><br>CONCLUSION: The study reports on the short-term effectiveness and tolerability of brolucizumab therapy in the management of nAMD in both treatment-na&#xef;ve and switch eyes. Brolucizumab was observed to have a favourable benefit-risk profile, and study results were within the known safety profile, with no instances of intraocular inflammation.},
}
@article {pmid37580905,
year = {2023},
author = {Matsevich, C and Gopalakrishnan, P and Chang, N and Obolensky, A and Beryozkin, A and Salameh, M and Kostic, C and Sharon, D and Arsenijevic, Y and Banin, E},
title = {Gene augmentation therapy attenuates retinal degeneration in a knockout mouse model of Fam161a retinitis pigmentosa.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {31},
number = {10},
pages = {2948-2961},
pmid = {37580905},
issn = {1525-0024},
mesh = {Mice ; Animals ; Humans ; *Retinal Degeneration/genetics/therapy/pathology ; Mice, Knockout ; Eye Proteins/genetics/metabolism ; *Retinitis Pigmentosa/genetics/therapy/metabolism ; Retina/metabolism ; Electroretinography ; },
abstract = {Photoreceptor cell degeneration and death is the major hallmark of a wide group of human blinding diseases including age-related macular degeneration and inherited retinal diseases such as retinitis pigmentosa. In recent years, inherited retinal diseases have become the "testing ground" for novel therapeutic modalities, including gene and cell-based therapies. Currently there is no available treatment for retinitis pigmentosa caused by FAM161A biallelic pathogenic variants. In this study, we injected an adeno-associated virus encoding for the longer transcript of mFam161a into the subretinal space of P24-P29 Fam161a knockout mice to characterize the safety and efficacy of gene augmentation therapy. Serial in vivo assessment of retinal function and structure at 3, 6, and 8 months of age using the optomotor response test, full-field electroretinography, fundus autofluorescence, and optical coherence tomography imaging as well as ex vivo quantitative histology and immunohistochemical studies revealed a significant structural and functional rescue effect in treated eyes accompanied by expression of the FAM161A protein in photoreceptors. The results of this study may serve as an important step toward future application of gene augmentation therapy in FAM161A-deficient patients by identifying a promising isoform to rescue photoreceptors and their function.},
}
@article {pmid37580831,
year = {2023},
author = {Barreto, P and Farinha, C and Coimbra, R and Cachulo, ML and Melo, JB and Lechanteur, Y and Hoyng, CB and Cunha-Vaz, J and Silva, R},
title = {Interaction between genetics and the adherence to the Mediterranean diet: the risk for age-related macular degeneration. Coimbra Eye Study Report 8.},
journal = {Eye and vision (London, England)},
volume = {10},
number = {1},
pages = {38},
pmid = {37580831},
issn = {2326-0254},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the macula. Different factors, environmental, genetic and lifestyle, contribute to its onset and progression. However, how they interconnect to promote the disease, or its progression, is still unclear. With this work, we aim to assess the interaction of the genetic risk for AMD and the adherence to the Mediterranean diet in the Coimbra Eye Study.<br><br>METHODS: Enrolled subjects (n&#x2009;=&#x2009;612) underwent ophthalmological exams and answered a food questionnaire. Adherence to the Mediterranean diet was assessed with mediSCORE. An overall value was calculated for each participant, ranging from 0 to 9, using the sum of 9 food groups, and a cut off value of &#x2265;&#x2009;6 was considered high adherence. Rotterdam Classification was used for grading. Participants' genotyping was performed in collaboration with The European Eye Epidemiology Consortium. The genetic risk score (GRS) was calculated for each participant considering the number of alleles at each variant and their effect size. Interaction was assessed with additive and multiplicative models, adjusted for age, sex, physical exercise, and smoking.<br><br>RESULTS: The AMD risk was reduced by 60% in subjects with high adherence to the Mediterranean diet compared to subjects with low adherence to the Mediterranean diet. Combined effects of having low adherence to the Mediterranean diet and high GRS led to almost a 5-fold increase in the risk for AMD, compared to low GRS and high adherence to the Mediterranean diet. The multiplicative scale suggested a multiplicative interaction, although not statistically significant [odds ratio (OR)&#x2009;=&#x2009;1.111, 95% CI 0.346-3.569, P&#x2009;=&#x2009;0.859]. The additive model showed a causal positive effect of the interaction of GRS and adherence to the Mediterranean diet: relative excess risk due to interaction (RERI)&#x2009;=&#x2009;150.9%, (95% CI: -&#x2009;0.414 to 3.432, P&#x2009;=&#x2009;0.062), attributable proportion due to interaction (AP)&#x2009;=&#x2009;0.326 (95% CI: -&#x2009;0.074 to 0.726, P&#x2009;=&#x2009;0.055) and synergy index (SI)&#x2009;=&#x2009;1.713 (95% CI: 0.098-3.329, P&#x2009;=&#x2009;0.019). High GRS people benefited from adhering to the Mediterranean diet with a 60%&#xa0;risk reduction. For low-GRS subjects, a risk reduction was also seen, but not significantly.<br><br>CONCLUSIONS: Genetics and Mediterranean diet interact to protect against AMD, proving there is an interplay between genetics and environmental factors.<br><br>TRIAL REGISTRATION: The AMD Incidence (NCT02748824) and Lifestyle and Food Habits Questionnaire in the Portuguese Population Aged 55 or More (NCT01715870) studies are registered at www.<br><br>CLINICALTRIALS: gov .&#xa0;Five-year Incidence of Age-related Macular Degeneration in the Central Region of Portugal (AMD IncidencePT); NCT02748824: date of registration: 22/04/16.&#xa0;Lifestyle and Food Habits Questionnaire in the Portuguese Population Aged 55 or More; NCT01715870: date of registration: 29/10/12.},
}
@article {pmid37579530,
year = {2023},
author = {Esteves, F and Brito, D and Rajado, AT and Silva, N and Apolónio, J and Roberto, VP and Araújo, I and Nóbrega, C and Castelo-Branco, P and Bragança, J and , },
title = {Reprogramming iPSCs to study age-related diseases: Models, therapeutics, and clinical trials.},
journal = {Mechanisms of ageing and development},
volume = {214},
number = {},
pages = {111854},
doi = {10.1016/j.mad.2023.111854},
pmid = {37579530},
issn = {1872-6216},
mesh = {Humans ; *Induced Pluripotent Stem Cells ; *Pluripotent Stem Cells ; Cell Differentiation ; *Adult Stem Cells ; Aging ; },
abstract = {The unprecedented rise in life expectancy observed in the last decades is leading to a global increase in the ageing population, and age-associated diseases became an increasing societal, economic, and medical burden. This has boosted major efforts in the scientific and medical research communities to develop and improve therapies to delay ageing and age-associated functional decline and diseases, and to expand health span. The establishment of induced pluripotent stem cells (iPSCs) by reprogramming human somatic cells has revolutionised the modelling and understanding of human diseases. iPSCs have a major advantage relative to other human pluripotent stem cells as their obtention does not require the destruction of embryos like embryonic stem cells do, and do not have a limited proliferation or differentiation potential as adult stem cells. Besides, iPSCs can be generated from somatic cells from healthy individuals or patients, which makes iPSC technology a promising approach to model and decipher the mechanisms underlying the ageing process and age-associated diseases, study drug effects, and develop new therapeutic approaches. This review discusses the advances made in the last decade using iPSC technology to study the most common age-associated diseases, including age-related macular degeneration (AMD), neurodegenerative and cardiovascular diseases, brain stroke, cancer, diabetes, and osteoarthritis.},
}
@article {pmid37578220,
year = {2023},
author = {Esh, Z and Suresh, S and Ortolan, D and Farnoodian, M and Bose, D and Ryu, J and Volkov, A and Bharti, K and Sharma, R},
title = {LipidUNet-Machine Learning-Based Method of Characterization and Quantification of Lipid Deposits Using iPSC-Derived Retinal Pigment Epithelium.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {197},
pages = {},
pmid = {37578220},
issn = {1940-087X},
support = {ZIA EY000532/ImNIH/Intramural NIH HHS/United States ; ZIA EY000533/ImNIH/Intramural NIH HHS/United States ; ZIA EY000559/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Retinal Pigment Epithelium ; *Induced Pluripotent Stem Cells ; Retina ; *Retinal Degeneration/pathology ; Lipids ; },
abstract = {The retinal pigment epithelium (RPE) is a monolayer of hexagonal cells located at the back of the eye. It provides nourishment and support to photoreceptors and choroidal capillaries, performs phagocytosis of photoreceptor outer segments (POS), and secretes cytokines in a polarized manner for maintaining the homeostasis of the outer retina. Dysfunctional RPE, caused by mutations, aging, and environmental factors, results in the degeneration of other retinal layers and causes vision loss. A hallmark phenotypic feature of degenerating RPE is intra and sub-cellular lipid-rich deposits. These deposits are a common phenotype across different retinal degenerative diseases. To reproduce the lipid deposit phenotype of monogenic retinal degenerations in vitro, induced pluripotent stem cell-derived RPE (iRPE) was generated from patients' fibroblasts. Cell lines generated from patients with Stargardt and Late-onset retinal degeneration (L-ORD) disease were fed with POS for 7 days to replicate RPE physiological function, which caused POS phagocytosis-induced pathology in these diseases. To generate a model for age-related macular degeneration (AMD), a polygenic disease associated with alternate complement activation, iRPE was challenged with alternate complement anaphylatoxins. The intra and sub-cellular lipid deposits were characterized using Nile Red, boron-dipyrromethene (BODIPY), and apolipoprotein E (APOE). To quantify the density of lipid deposits, a machine learning-based software, LipidUNet, was developed. The software was trained on maximum-intensity projection images of iRPE on culture surfaces. In the future, it will be trained to analyze three-dimensional (3D) images and quantify the volume of lipid droplets. The LipidUNet software will be a valuable resource for discovering drugs that decrease lipid accumulation in disease models.},
}
@article {pmid37577931,
year = {2023},
author = {Fiedorowicz, J and Dobrzynska, MM},
title = {Lutein and zeaxanthin - radio- and chemoprotective properties. Mechanism and possible use.},
journal = {Roczniki Panstwowego Zakladu Higieny},
volume = {74},
number = {3},
pages = {257-264},
doi = {10.32394/rpzh.2023.0266},
pmid = {37577931},
issn = {0035-7715},
mesh = {Humans ; Animals ; Mice ; Lutein/pharmacology/metabolism ; Zeaxanthins/pharmacology/therapeutic use ; Xanthophylls/metabolism/therapeutic use ; *Macular Degeneration/prevention &amp; control/drug therapy/metabolism ; Diet ; *Neoplasms ; },
abstract = {Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum light absorbance, including UV. This property, and fact, that these xanthophylls are accumulated by human eye's macula, leads to eye's protective functions of them including protection from age-related macular degeneration (AMD). Also, antioxidative features of lutein and zeaxanthin are boosting overall health of human body. Numerous studies proves anti-inflammatory and protective attributes of these compounds, based on many, different mechanisms. One of them is regulating redox potential in cells, and impact on expression of linked genes. In preventing of eye diseases, an important gene that is regulated by lutein and zeaxanthin is the Nrf2 gene, whose increased activity leads to optimizing the cellular response to reactive oxygen species (ROS) and preventing related diseases. Other research confirms antiproliferative properties of mentioned compounds in case of certain human cancer cell lines. There are e.g.: HepG2 (hepatitis cancer), MCF-7 (breast cancer), which treated in vitro with lutein solution showed reduction of cell growth. Lutein alone, during in vivo studies conducted on mice, exhibited also radioprotective properties, positively affecting the vitality of animals. Lutein provides also increasing of tolerance to UV radiation, reducing inflammatory processes in the skin and preventing oncogenesis. Low intake of lutein and zeaxanthin, associated with "western diet", rich in simple carbohydrates and processed food, common in developed countries, including Poland, is linked with diabetes and obesity incidence. Assuming, lutein and zeaxanthin significantly affect the well-being of the human body, and their appropriate amount in diet can help reduce risk of many diseases. For supplementation, the optimized dosage of these xanthophylls includes doses of 10 mg for lutein and 2 mg for zeaxanthin, and it is recommended to consume along with fats or meals rich in fats.},
}
@article {pmid37577701,
year = {2023},
author = {Wada, I and Mori, K and Sreekumar, PG and Ji, R and Spee, C and Hong, E and Ishikawa, K and Sonoda, KH and Kannan, R},
title = {Characterization and contribution of RPE senescence to Age-related macular degeneration in Tnfrsf10 knock out mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.08.04.552052},
pmid = {37577701},
issn = {2692-8205},
support = {R01 EY030141/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND: Retinal pigment epithelial cells (RPE) play vital role in the pathogenesis of age-related macular degeneration (AMD). Our laboratory has shown that RPE cellular senescence contributed to the pathophysiology of experimental AMD, and SASP members are involved in this process. Recently, we presented confirmatory evidence to earlier GWAS studies that dysregulation of tumor necrosis factor receptor superfamily 10A (TNFRSF10A) dysregulation leads to AMD development and is linked to RPE dysfunction. This study aims to investigate the contribution of RPE senescence to AMD pathophysiology using TNFRSF10A silenced human RPE (hRPE) cells and Tnfrsf10 KO mice.<br><br>METHODS: Sub-confluent primary hRPE cells and TNFRSF10A silenced hRPE were exposed to stress-induced premature senescence with H2O2 (500 &#x3bc;M, 48h), and senescence-associated markers (&#x3b2;gal, p16, and p21) were analyzed by RT-PCR and WB analysis. The effect of H2O2-induced senescence in non-silenced and silenced hRPE on OXPHOS and glycolysis was determined using Seahorse XF96 analyzer. Male C57BL/6J Tnfrsf10 KO (Tnfrsf10 [-/-]) mice were used to study the regulation of senescence by TNFRSF10A in vivo . Expression of p16 and p21 in control and KO mice of varying ages were determined by RT-PCR, WB, and immunostaining analysis.<br><br>RESULTS: The senescence-associated p16 and p21 showed a significant (p < 0.01) upregulation with H2O2 induction at the gene (1.8- and 3-fold) and protein (3.2- and 4-fold) levels in hRPE cells. The protein expression of p16 and p21 was further significantly increased by co-treatment with siRNA (p < 0.05 vs. H2O2). Mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) (pmol/min/total DNA) increased with senescence induction by H2O2 for 48h in control RPE, and knockdown of TNFRSF10A caused a further increase in OCR and ECAR. In addition, co-treatment with PKC activator significantly improved all parameters. Similarly, in vivo studies showed upregulation of p16 and p21 by RT-PCR, WB, and immunostaining analysis in RPE/choroid of Tnfrsf10 KO mice. When subjected to examination across distinct age groups, namely young (1-3 months), middle (6-9 months), and old (12-15 months) mice, a discernible age-related elevation in the expression of p16 and p21 was observed.<br><br>CONCLUSIONS: Our findings suggest that TNRSF10A is a regulator of regulates in RPE senescence. Further work on elucidating pathways of senescence will facilitate the development of new therapeutic targets for AMD.},
}
@article {pmid37575875,
year = {2023},
author = {Lee, IK and Xie, R and Luz-Madrigal, A and Min, S and Zhu, J and Jin, J and Edwards, KL and Phillips, MJ and Ludwig, AL and Gamm, DM and Gong, S and Ma, Z},
title = {Micromolded honeycomb scaffold design to support the generation of a bilayered RPE and photoreceptor cell construct.},
journal = {Bioactive materials},
volume = {30},
number = {},
pages = {142-153},
pmid = {37575875},
issn = {2452-199X},
abstract = {Age-related macular degeneration (AMD) causes blindness due to loss of retinal pigment epithelium (RPE) and photoreceptors (PRs), which comprise the two outermost layers of the retina. Given the small size of the macula and the importance of direct contact between RPE and PRs, the use of scaffolds for targeted reconstruction of the outer retina in later stage AMD and other macular dystrophies is particularly attractive. We developed microfabricated, honeycomb-patterned, biodegradable poly(glycerol sebacate) (PGS) scaffolds to deliver organized, adjacent layers of RPE and PRs to the subretinal space. Furthermore, an optimized process was developed to photocure PGS, shortening scaffold production time from days to minutes. The resulting scaffolds robustly supported the seeding of human pluripotent stem cell-derived RPE and PRs, either separately or as a dual cell-layered construct. These advanced, economical, and versatile scaffolds can accelerate retinal cell transplantation efforts and benefit patients with AMD and other retinal degenerative diseases.},
}
@article {pmid37572871,
year = {2024},
author = {Patel, NA and Al-Khersan, H and Yannuzzi, NA and Lin, J and Smiddy, WE},
title = {A Cost-Effectiveness Analysis of Pegcetacoplan for the Treatment of Geographic Atrophy.},
journal = {Ophthalmology. Retina},
volume = {8},
number = {1},
pages = {25-31},
doi = {10.1016/j.oret.2023.08.003},
pmid = {37572871},
issn = {2468-6530},
mesh = {Aged ; Humans ; United States ; *Geographic Atrophy/diagnosis/therapy ; Cost-Effectiveness Analysis ; Medicare ; Atrophy ; },
abstract = {PURPOSE: To evaluate the cost-effectiveness of the treatment of geography atrophy (GA) with intravitreal pegcetacoplan and to identify utility-measurement surrogates.<br><br>DESIGN: Cost analysis based on data from a published study.<br><br>SUBJECTS: None; based on data from published sham control compared with 2 treatment groups in the index study.<br><br>METHODS: Costs were based on 2022 Medicare reimbursement data. Specific outcomes were extrapolated from the DERBY and OAKS trials. Assumptions were made for the lifetime analysis based on a theoretical logistic growth model of the atrophy.<br><br>OUTCOME MEASURES: Cost, cost utility, cost per quality-adjusted life-year, and cost per area of GA (in US$).<br><br>RESULTS: The costs to treat GA in every month (EM) and every-other-month (EOM) treatment groups over the 2 years as reported were $70 000 and $34 600, respectively. The costs per area of delaying GA for 2 years in all patients were $87 300/mm[2] (EM) and $49 200/mm[2] (EOM), and in initially extrafoveal patients, $53 900/mm[2] (EM) and $32 100/mm[2] (EOM). The costs per day of delaying GA for 2 years were $295 (EM) and $170 (EOM); the marginal cost (EM vs. EOM) per retinal pigment epithelium cell saved was $30. The modeled lifetime costs were $350 000 (EM) and $172 000 (EOM), or $309 000/mm[2] (EM) and $180 000 (EOM) /mm[2]. The modeled time to 95% atrophy at 13 years was delayed by 2.5 years (EM) and 2.1 years (EOM). The costs/quality-adjusted life-year gained based on modeled visual loss with 95% atrophy were $706 000 (EM) and $397 000 (EOM).<br><br>CONCLUSION: Treatment of GA with intravitreal pegcetacoplan EOM was more cost effective than EM. Treatment of extrafoveal lesions yielded greater utility than the treatment of the entire group. As atrophy progression approaches an upper limit, the marginal cost/benefit ratios increase.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37571490,
year = {2023},
author = {Khan, A and Pin, K and Aziz, A and Han, JW and Nam, Y},
title = {Optical Coherence Tomography Image Classification Using Hybrid Deep Learning and Ant Colony Optimization.},
journal = {Sensors (Basel, Switzerland)},
volume = {23},
number = {15},
pages = {},
pmid = {37571490},
issn = {1424-8220},
support = {NRF-2021R1A2C1010362//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Macular Edema ; *Diabetic Retinopathy/diagnostic imaging ; *Deep Learning ; Tomography, Optical Coherence/methods ; *Retinal Diseases ; Algorithms ; },
abstract = {Optical coherence tomography (OCT) is widely used to detect and classify retinal diseases. However, OCT-image-based manual detection by ophthalmologists is prone to errors and subjectivity. Thus, various automation methods have been proposed; however, improvements in detection accuracy are required. Particularly, automated techniques using deep learning on OCT images are being developed to detect various retinal disorders at an early stage. Here, we propose a deep learning-based automatic method for detecting and classifying retinal diseases using OCT images. The diseases include age-related macular degeneration, branch retinal vein occlusion, central retinal vein occlusion, central serous chorioretinopathy, and diabetic macular edema. The proposed method comprises four main steps: three pretrained models, DenseNet-201, InceptionV3, and ResNet-50, are first modified according to the nature of the dataset, after which the features are extracted via transfer learning. The extracted features are improved, and the best features are selected using ant colony optimization. Finally, the best features are passed to the k-nearest neighbors and support vector machine algorithms for final classification. The proposed method, evaluated using OCT retinal images collected from Soonchunhyang University Bucheon Hospital, demonstrates an accuracy of 99.1% with the incorporation of ACO. Without ACO, the accuracy achieved is 97.4%. Furthermore, the proposed method exhibits state-of-the-art performance and outperforms existing techniques in terms of accuracy.},
}
@article {pmid37571296,
year = {2023},
author = {Blasiak, J and Chojnacki, J and Szczepanska, J and Fila, M and Chojnacki, C and Kaarniranta, K and Pawlowska, E},
title = {Epigallocatechin-3-Gallate, an Active Green Tea Component to Support Anti-VEGFA Therapy in Wet Age-Related Macular Degeneration.},
journal = {Nutrients},
volume = {15},
number = {15},
pages = {},
pmid = {37571296},
issn = {2072-6643},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/metabolism ; Tea ; Retina/metabolism ; *Macular Degeneration/drug therapy ; },
abstract = {Age-related macular degeneration (AMD) is a largely incurable disease and an emerging problem in aging societies. It occurs in two forms, dry and wet (exudative, neovascular), which may cause legal blindness and sight loss. Currently, there is not any effective treatment for dry AMD. Meanwhile, repeated intravitreal injections with antibodies effective against vascular endothelial growth factor A (VEGFA) slow down wet AMD progression but are not free from complications. (-)-Epigallocatechin-3-gallate (EGCG) is an active compound of green tea, which exerts many beneficial effects in the retinal pigment epithelium and the neural retina. It has been reported to downregulate the VEGFA gene by suppressing its activators. The inhibition of mitogen-activated protein kinases 1 and 3 (MAPK1 and MAPK3) may lie behind the antiangiogenic action of EGCG mediated by VEGFA. EGCG exerts protective effects against UV-induced damage to retinal cells and improves dysfunctional autophagy. EGCG may also interact with the mechanistic target rapamycin (MTOR) and unc-51-like autophagy activating kinase (ULK1) to modulate the interplay between autophagy and apoptosis. Several other studies report beneficial effects of EGCG on the retina that may be related to wet AMD. Therefore, controlled clinical trials are needed to verify whether diet supplementation with EGCG or green tea consumption may improve the results of anti-VEGFA therapy in wet AMD.},
}
@article {pmid37569464,
year = {2023},
author = {Wang, X and Wang, T and Lam, E and Alvarez, D and Sun, Y},
title = {Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation.},
journal = {International journal of molecular sciences},
volume = {24},
number = {15},
pages = {},
pmid = {37569464},
issn = {1422-0067},
support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01 EY030140/EY/NEI NIH HHS/United States ; R01EY030140, R01EY029238/NH/NIH HHS/United States ; },
mesh = {Infant, Newborn ; Humans ; Immune Privilege ; Retina/physiology ; *Eye Diseases ; Inflammation ; *Retinal Diseases ; *Diabetic Retinopathy ; },
abstract = {The eye is an immune privileged tissue that insulates the visual system from local and systemic immune provocation to preserve homeostatic functions of highly specialized retinal neural cells. If immune privilege is breached, immune stimuli will invade the eye and subsequently trigger acute inflammatory responses. Local resident microglia become active and release numerous immunological factors to protect the integrity of retinal neural cells. Although acute inflammatory responses are necessary to control and eradicate insults to the eye, chronic inflammation can cause retinal tissue damage and cell dysfunction, leading to ocular disease and vision loss. In this review, we summarized features of immune privilege in the retina and the key inflammatory responses, factors, and intracellular pathways activated when retinal immune privilege fails, as well as a highlight of the recent clinical and research advances in ocular immunity and ocular vascular diseases including retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy.},
}
@article {pmid37568546,
year = {2023},
author = {Kishi, M and Miki, A and Kamimura, A and Okuda, M and Matsumiya, W and Imai, H and Kusuhara, S and Nakamura, M},
title = {Short-Term Outcomes of Faricimab Treatment in Aflibercept-Refractory Eyes with Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {15},
pages = {},
pmid = {37568546},
issn = {2077-0383},
abstract = {To evaluate the functional and anatomical effects of switching to faricimab for patients with neovascular age-related macular degeneration (nAMD) refractory to intravitreal aflibercept, this retrospective study evaluated patients with nAMD who received intravitreal injections of aflibercept (IVA) every <8 weeks and were switched to faricimab. After switching, the patients were treated with a treatment and extended regimen that started with the interval just before switching and received at least three injections. We evaluated changes in the best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), treatment interval, and presence of retinal fluid. Overall, 55 eyes from 55 patients were examined. After three injections of faricimab, the BCVA and CCT did not change significantly. However, the CRT decreased significantly (p < 0.05), the injection interval was significantly extended (7.5 ± 2.3 vs. 5.9 ± 1.5 weeks, p < 0.01), and the rates of the presence of intraretinal fluid and subretinal fluid decreased significantly to 16.4% and 40% of eyes, respectively (both p < 0.01). An ocular adverse event (retinal pigment epithelium tear) developed in one eye. Switching to faricimab was effective for anatomic changes. It may be an additional treatment option for some eyes refractory to IVA.},
}
@article {pmid37568533,
year = {2023},
author = {Cruz-Pimentel, M and Wu, L},
title = {Complement Inhibitors for Advanced Dry Age-Related Macular Degeneration (Geographic Atrophy): Some Light at the End of the Tunnel?.},
journal = {Journal of clinical medicine},
volume = {12},
number = {15},
pages = {},
pmid = {37568533},
issn = {2077-0383},
abstract = {Geographic atrophy (GA) affects around 5 million individuals worldwide. Genome-wide, histopathologic, in vitro and animal studies have implicated the activation of the complement system and chronic local inflammation in the pathogenesis of GA. Recently, clinical trials have demonstrated that an intravitreal injection of pegcetacoplan, a C3 inhibitor, and avacincaptad pegol, a C5 inhibitor, both statistically significantly reduce the growth of GA up to 20% in a dose-dependent fashion. Furthermore, the protective effect of both pegcetacoplan and avacincaptad appear to increase with time. However, despite these anatomic outcomes, visual function has not improved as these drugs appear to only slow down the degenerative process. Unexpected adverse events included conversion to exudative NV-AMD with both drugs. Occlusive retinal vasculitis and anterior ischemic optic neuropathy have been reported in pegcetacoplan-treated eyes.},
}
@article {pmid37567751,
year = {2023},
author = {Nguyen, H and Di Tanna, GL and Coxon, K and Brown, J and Ren, K and Ramke, J and Burton, MJ and Gordon, I and Zhang, JH and Furtado, J and Mdala, S and Kitema, GF and Keay, L},
title = {Associations between vision impairment and vision-related interventions on crash risk and driving cessation: systematic review and meta-analysis.},
journal = {BMJ open},
volume = {13},
number = {8},
pages = {e065210},
pmid = {37567751},
issn = {2044-6055},
support = {/WT_/Wellcome Trust/United Kingdom ; 207472/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; 20190426_PH2/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Visual Acuity ; Ranibizumab ; Accidents, Traffic/prevention &amp; control ; *Macular Degeneration/epidemiology ; Vision Disorders/epidemiology ; *Cataract/complications ; },
abstract = {OBJECTIVES: To systematically investigate the associations between vision impairment and risk of motor vehicle crash (MVC) involvement, and evaluate vision-related interventions to reduce MVCs.<br><br>DESIGN: Medline (Ovid), EMBASE and Global Health electronic databases were systematically searched from inception to March 2022 for observational and interventional English-language studies. Screening, data extraction and appraisals using the Joanna Briggs Institute appraisal tools were completed by two reviewers independently. Where appropriate, measures of association were converted into risk ratios (RRs) or ORs for meta-analysis.<br><br>PARTICIPANTS: Drivers of four-wheeled vehicles of all ages with no cognitive declines.<br><br>MVC involvement (primary) and driving cessation (secondary).<br><br>RESULTS: 101 studies (n=778&#x2009;052) were included after full-text review. 57 studies only involved older drivers (&#x2265;65 years) and 85 were in high-income settings. Heterogeneity in the data meant that most meta-analyses were underpowered as only 25 studies, further split into different groups of eye diseases and measures of vision, could be meta-analysed. The limited evidence from the meta-analyses suggests that visual field defects (four studies; RR 1.51 (95% CI 1.23, 1.85); p<0.001; I[2]=46.79%), and contrast sensitivity (two studies; RR 1.40 (95% CI 1.08, 1.80); p=0.01, I[2]=0.11%) and visual acuity loss (five studies; RR 1.21 (95% CI 1.02, 1.43); p=0.03, I[2]=28.49%) may increase crash risk. The results are more inconclusive for available evidence for associations of glaucoma (five studies, RR 1.27 (95% CI 0.67, 2.42); p=0.47; I[2]=93.48%) and cataract (two studies RR 1.15 (95% CI 0.97, 1.36); p=0.11; I[2]=3.96%) with crashes. Driving cessation may also be linked with glaucoma (two studies; RR 1.62 (95% CI 1.20, 2.19); p<0.001, I[2]=22.45%), age-related macular degeneration (AMD) (three studies; RR 2.21 (95% CI 1.47, 3.31); p<0.001, I[2]=75.11%) and reduced contrast sensitivity (three studies; RR 1.30 (95% CI 1.05, 1.61); p=0.02; I[2]=63.19%). Cataract surgery halved MVC risk (three studies; RR 0.55 (95% CI 0.34, 0.92); p=0.02; I[2]=97.10). Ranibizumab injections (four randomised controlled trials) prolonged driving in persons with AMD.<br><br>CONCLUSION: Impaired vision identified through a variety of measures is associated with both increased MVC involvement and cessation. Cataract surgery can reduce MVC risk. Despite literature being highly heterogeneous, this review shows that detection of vision problems and appropriate treatment are critical to road safety.<br><br>PROSPERO REGISTRATION NUMBER: CRD42020172153.},
}
@article {pmid37566944,
year = {2023},
author = {Tong, Y and Wu, Y and Ma, J and Ikeda, M and Ide, T and Griffin, CT and Ding, XQ and Wang, S},
title = {Comparative mechanistic study of RPE cell death induced by different oxidative stresses.},
journal = {Redox biology},
volume = {65},
number = {},
pages = {102840},
pmid = {37566944},
issn = {2213-2317},
support = {P30 EY001583/EY/NEI NIH HHS/United States ; R01 EY033841/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Cell Death ; *Ferroptosis ; Lipids ; *Macular Degeneration/genetics/metabolism ; Oxidative Stress/physiology ; Reactive Oxygen Species/metabolism ; },
abstract = {Oxidative stress is hypothesized to drive the progression of age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cell layer is important for supporting the function of retina and is particularly susceptible to oxidative stress-induced cell death. How RPE cells die in AMD, especially in geographic atrophy (GA), a late stage of dry AMD, is still controversial. The goal of this study is to compare the features and mechanisms of RPE cell death induced by different oxidative stresses, to identify potential universal therapeutic targets for GA. RPE cell death was induced both in vitro and ex vivo by 4-Hydroxynonenal (4-HNE), a major product of lipid peroxidation, sodium iodate (NaIO3) that has been widely used to model RPE cell death in dry AMD, a ferroptosis inducer RAS-selective lethal 3 (RSL3) or a necroptosis inducer shikonin. We found that RPE necroptosis and ferroptosis show common and distinct features. Common features include receptor-interacting protein kinase (RIPK)1/RIPK3 activation and lipid reactive oxygen species (ROS) accumulation, although lipid ROS accumulation is much milder during necroptosis. This supports cross talk between RPE ferroptosis and necroptosis pathways and is consistent with the rescue of RPE necroptosis and ferroptosis by RIPK1 inhibitor Necrostatin-1 (Nec-1) or in Ripk3[-/-] RPE explants. Distinct feature includes activated mixed lineage kinase domain like pseudokinase (MLKL) that is translocated to the cell membrane during necroptosis, which is not happening in ferroptosis. This is consistent with the failure to rescue RPE ferroptosis by MLKL inhibitor necrosulfonamide (NSA) or in Mlkl[-/-] RPE explants. Using this framework, we found that 4-HNE and NaIO3 induced RPE cell death likely through necroptosis based on the molecular features and the rescuing effect by multiple inhibitors. Our studies suggest that multiple markers and inhibitors are required to distinguish RPE necroptosis and ferroptosis, and that necroptosis inhibitor Nec-1 could be a potential therapeutic compound for GA since it inhibits RIPK1/RIPK3 activation and lipid ROS accumulation occurred in both necroptosis and ferroptosis pathways.},
}
@article {pmid37566633,
year = {2023},
author = {Monavarfeshani, A and Yan, W and Pappas, C and Odenigbo, KA and He, Z and Segrè, AV and van Zyl, T and Hageman, GS and Sanes, JR},
title = {Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {34},
pages = {e2306153120},
pmid = {37566633},
issn = {1091-6490},
support = {K99 EY033457/EY/NEI NIH HHS/United States ; P50 HD105351/HD/NICHD NIH HHS/United States ; K12 EY016335/EY/NEI NIH HHS/United States ; F32 EY031930/EY/NEI NIH HHS/United States ; U01 MH105960/MH/NIMH NIH HHS/United States ; R21 EY028633/EY/NEI NIH HHS/United States ; T32 NS007473/NS/NINDS NIH HHS/United States ; R01 EY031424/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Transcriptome ; Endothelial Cells ; *Optic Disk ; *Glaucoma/genetics ; Optic Nerve ; Sclera ; },
abstract = {Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here, we used high-throughput single-nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in six extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases-for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ~151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the data presented here complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as the neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.},
}
@article {pmid37566304,
year = {2023},
author = {Yanagi, Y and Takahashi, K and Iida, T and Gomi, F and Morii, J and Kunikane, E and Sakamoto, T},
title = {Correction: Cost-Effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration in Japan.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2821-2822},
doi = {10.1007/s40123-023-00788-9},
pmid = {37566304},
issn = {2193-8245},
}
@article {pmid37566303,
year = {2023},
author = {Verma, A and Corradetti, G and He, Y and Nittala, MG and Nassisi, M and Velaga, SB and Haines, JL and Pericak-Vance, MA and Stambolian, D and Sadda, SR},
title = {Relationship between the distribution of intra-retinal hyper-reflective foci and the progression of intermediate age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {12},
pages = {3437-3447},
pmid = {37566303},
issn = {1435-702X},
mesh = {Humans ; Child, Preschool ; Disease Progression ; Retina ; *Macular Degeneration/complications ; *Macula Lutea ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; },
abstract = {PURPOSE: To assess the relationship between the distribution of intra-retinal hyper-reflective foci (IHRF) on optical coherence tomography (OCT) and progression of intermediate age-related macular degeneration (iAMD) over 2 years.<br><br>METHODS: Cirrus OCT volumes of the macula of subjects enrolled in the Amish Eye Study with 2 years of follow-up were evaluated for the presence of iAMD and IHRF at baseline. The IHRF were counted in a series of 5 sequential en face slabs from outer to inner retina. The number of IHRF in each slab at baseline and the change in IHRF from baseline to year 2 were correlated with progression to late AMD at 2 years.<br><br>RESULTS: Among 120 eyes from 71 patients with iAMD, 52 eyes (43.3%) of 42 patients had evidence of both iAMD and IHRF at baseline. Twenty-three eyes (19.0%) showed progression to late AMD after 2 years. The total IHRF count increased from 243 at baseline to 604 at 2 years, with a significant increase in the IHRF number in each slab, except for the innermost slab 5 which had no IHRF at baseline or follow-up. The IHRF count increased from 121 to 340 in eyes that showed progression to late AMD. The presence of IHRF in the outermost retinal slabs 1 and 2 was independently associated with a significant risk of progression to late AMD. A greater increase in IHRF count over 2 years in these same slabs 1 and 2 was also associated with a higher risk of conversion to late AMD.<br><br>CONCLUSIONS: The risk of progression to late AMD appears to be significantly associated with the distribution and extent of IHRF in the outermost retinal layers. This observation may point to significant pathophysiologic differences of IHRF in inner versus outer layers of the retina.},
}
@article {pmid37566302,
year = {2023},
author = {Blazaki, S and Blavakis, E and Chlouverakis, G and Bontzos, G and Chatziralli, I and Smoustopoulos, G and Dimitriou, E and Stavrakakis, A and Kabanarou, S and Xirou, T and Vavvas, DG and Tsilimbaris, MK},
title = {Evolution of macular atrophy in eyes with neovascular age-related macular degeneration compared to fellow non-neovascular eyes.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {12},
pages = {3425-3436},
pmid = {37566302},
issn = {1435-702X},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; Atrophy/drug therapy ; Ranibizumab ; Intravitreal Injections ; },
abstract = {PURPOSE: Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD).<br><br>METHODS: This retrospective study included 124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA.<br><br>RESULTS: MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study's follow-up, 45.1% of nAMD-E developed MA, compared to 16.5% of fellow eyes (p&#x2009;<&#x2009;0.001). When MA in the two eyes was compared in a synchronous paired manner over 4&#xa0;years, nAMD eyes had an average MA progression rate of 0.275&#xa0;mm/year versus 0.110&#xa0;mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (p&#x2009;<&#x2009;0.001), eye (p&#x2009;=&#x2009;0.003), and time-eye interaction (p&#x2009;<&#x2009;0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295&#xa0;mm/year vs. nAMD: 0.176&#xa0;mm/year) with a significant time-eye interaction (p&#x2009;=&#x2009;0.015).<br><br>CONCLUSIONS: In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.},
}
@article {pmid37565126,
year = {2023},
author = {Riazi Esfahani, P and Reddy, AJ and Nawathey, N and Ghauri, MS and Min, M and Wagh, H and Tak, N and Patel, R},
title = {Deep Learning Classification of Drusen, Choroidal Neovascularization, and Diabetic Macular Edema in Optical Coherence Tomography (OCT) Images.},
journal = {Cureus},
volume = {15},
number = {7},
pages = {e41615},
pmid = {37565126},
issn = {2168-8184},
abstract = {Background Age-related macular degeneration (AMD), diabetic retinopathy (DR), drusen, choroidal neovascularization (CNV), and diabetic macular edema (DME) are significant causes of visual impairment globally. Optical coherence tomography (OCT) imaging has emerged as a valuable diagnostic tool for these ocular conditions. However, subjective interpretation and inter-observer variability highlight the need for standardized diagnostic approaches. Methods This study aimed to develop a robust deep learning model using artificial intelligence (AI) techniques for the automated detection of drusen, CNV, and DME in OCT images. A diverse dataset of 1,528 OCT images from Kaggle.com was used for model training. The performance metrics, including precision, recall, sensitivity, specificity, F1 score, and overall accuracy, were assessed to evaluate the model's effectiveness. Results The developed model achieved high precision (0.99), recall (0.962), sensitivity (0.985), specificity (0.987), F1 score (0.971), and overall accuracy (0.987) in classifying diseased and healthy OCT images. These results demonstrate the efficacy and efficiency of the model in distinguishing between retinal pathologies. Conclusion The study concludes that the developed deep learning model using AI techniques is highly effective in the automated detection of drusen, CNV, and DME in OCT images. Further validation studies and research efforts are necessary to evaluate the generalizability and integration of the model into clinical practice. Collaboration between clinicians, policymakers, and researchers is essential for advancing diagnostic tools and management strategies for AMD and DR. Integrating this technology into clinical workflows can positively impact patient care, particularly in settings with limited access to ophthalmologists. Future research should focus on collecting independent datasets, addressing potential biases, and assessing real-world effectiveness. Overall, the use of machine learning algorithms in conjunction with OCT imaging holds great potential for improving the detection and management of drusen, CNV, and DME, leading to enhanced patient outcomes and vision preservation.},
}
@article {pmid37562440,
year = {2023},
author = {Kim, J and Lee, SJ and Park, TK and Sun, HJ and Kim, HD and Cho, IH and Han, JW and Choi, KS},
title = {Short-term Efficacy and Safety of Intravitreal Brolucizumab Injection for Treatment-Naive Exudate Age-related Macular Degeneration: A Multicenter Study.},
journal = {Korean journal of ophthalmology : KJO},
volume = {37},
number = {5},
pages = {365-372},
pmid = {37562440},
issn = {2092-9382},
support = {//Soonchunhyang University/ ; },
abstract = {PURPOSE: To compare short-term efficacy and safety of intravitreal brolucizumab injection with aflibercept in treatment-naive neovascular age-related macular degeneration (nAMD) patients.<br><br>METHODS: A total of 59 eyes from 59 treatment-naive nAMD patients in three hospitals were retrospectively reviewed. Of which, 27 patients underwent intravitreal brolucizumab injections and 32 received aflibercept. After monthly consecutive three injections, best-corrected visual acuity (BCVA; in logarithm of minimal angle of resolution [logMAR]), central macular thickness (CMT), dry macula achievement rate, and intraocular inflammation (IOI) incidence were compared.<br><br>RESULTS: After loading-phase treatment, BCVA was significantly increased from 0.48 &#xb1; 0.30 logMAR at baseline to 0.33 &#xb1; 0.21 logMAR at 3 months in the brolucizumab group (p = 0.002) and 0.40 &#xb1; 0.39 logMAR at baseline to 0.33 &#xb1; 0.36 logMAR at 3 months in the aflibercept group (p = 0.007). But there was no significant difference in BCVA improvement at 3 months between the two groups. CMT significantly decreased from 429.67 &#xb1; 250.59 &#x3bc;m at baseline to 210.67 &#xb1; 93.53 &#x3bc;m at 3 months in the brolucizumab group and from 346.69 &#xb1; 159.09 &#x3bc;m to 234.52 &#xb1; 83.42 &#x3bc;m in the aflibercept group (both p < 0.001). The amount of CMT reduction was significantly greater in the brolucizumab group after 3 months (p = 0.036). In typical AMD eyes, brolucizumab showed similar BCVA improvement but better CMT reduction at 3 months (p = 0.018). Dry macula achievement rate was not significantly different between the two groups. One IOI was observed in the brolucizumab group.<br><br>CONCLUSIONS: Intravitreal injections of brolucizumab and aflibercept showed similar anatomical and functional outcomes. But CMT reduction was greater in the brolucizumab group. One IOI was identified, which was tolerable for topical agents. These results suggest that brolucizumab could be a novel first line treatment option for treating naive nAMD patients.},
}
@article {pmid37561146,
year = {2023},
author = {Joo, CW and Choi, HG and Kim, KL and Park, SP and Kim, YK},
title = {Factors affecting optical coherence tomography angiography signal strength index in patients receiving intravitreal injection treatment.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {12},
pages = {3403-3413},
pmid = {37561146},
issn = {1435-702X},
support = {2021R1F1A1057121//Ministry of Science and ICT, South Korea/ ; KARD-2016001//Korean Association of Retinal Degeneration/ ; },
mesh = {Humans ; Intravitreal Injections ; *Macular Edema/diagnosis/drug therapy/etiology ; *Diabetic Retinopathy/drug therapy ; Tomography, Optical Coherence ; Angiography ; Treatment Outcome ; Angiogenesis Inhibitors ; },
abstract = {PURPOSE: To investigate the clinical factors affecting optical coherence tomography angiography (OCTA) signal strength index (SSI) and its change after intravitreal injection treatment in patients with retinal disorders.<br><br>METHODS: OCTA data from 186 eyes of 166 patients with various retinal disorders including age-related macular degeneration, diabetic macular edema (DME), and retinal vein occlusions who received intravitreal injections were analyzed. The associations between SSI and clinical factors, including age, best-corrected visual acuity (BCVA), media opacity severity, and central macular thickness (CMT), were evaluated both before and after injection.<br><br>RESULTS: After injection, BCVA improved and CMT decreased significantly, and SSI increased significantly (p&#x2009;=&#x2009;0.030). BCVA showed a significant positive correlation with media opacity severity before and after injection and with CMT only before injection. In the multivariate analysis, age, presence of DME, BCVA, and media opacity severity were negatively associated with SSI both before and after injection, while CMT was negatively associated with SSI only before injection. After injection, a negative correlation was found between SSI change and both BCVA and CMT change.<br><br>CONCLUSION: Our findings suggest that OCTA SSI is influenced by various clinical factors, including age, visual acuity, media opacity severity, and macular thickening, especially in cases of DME. The results also indicate that SSI may decrease in patients with macular disorders due to the presence of macular edema and the associated decrease in visual acuity. Therefore, it is crucial to consider these factors when interpreting OCTA data and ensure an adequate level of SSI.},
}
@article {pmid37560825,
year = {2023},
author = {Rapata, M and Cunningham, W and Harwood, M and Niederer, R},
title = {Te hauora karu o te iwi Māori: A comprehensive review of Māori eye health in Aotearoa/New Zealand.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {51},
number = {7},
pages = {714-727},
doi = {10.1111/ceo.14279},
pmid = {37560825},
issn = {1442-9071},
mesh = {Humans ; *Maori People ; New Zealand/epidemiology ; *Eye ; *Health Status ; },
abstract = {This article provides a summary of available data on Māori ocular health, highlighting significant disparities between Māori and non-Māori populations. Māori are more likely to develop diabetes, sight-threatening retinopathy and keratoconus, and present for cataract surgery earlier with more advanced disease. Limited data exists for macular degeneration and glaucoma, but there is some suggestion that Māori may have lower prevalence rates. The article emphasises the urgent need for robust national data on Māori ocular health to enable targeted interventions and funding allocation. Achieving equity for Māori in all aspects of health, including ocular health, requires concerted efforts from all stakeholders.},
}
@article {pmid37560455,
year = {2023},
author = {Brown, LN and Barth, JL and Jafri, S and Rumschlag, JA and Jenkins, TR and Atkinson, C and Lang, H},
title = {Complement factor B is essential for the proper function of the peripheral auditory system.},
journal = {Frontiers in neurology},
volume = {14},
number = {},
pages = {1214408},
pmid = {37560455},
issn = {1664-2295},
support = {S10 OD018113/OD/NIH HHS/United States ; P20 GM103499/GM/NIGMS NIH HHS/United States ; P30 GM103342/GM/NIGMS NIH HHS/United States ; R01 DC012058/DC/NIDCD NIH HHS/United States ; T32 DC014435/DC/NIDCD NIH HHS/United States ; R56 DC012058/DC/NIDCD NIH HHS/United States ; TL1 TR000145/TR/NCATS NIH HHS/United States ; C06 RR014516/RR/NCRR NIH HHS/United States ; P50 DC000422/DC/NIDCD NIH HHS/United States ; K18 DC018517/DC/NIDCD NIH HHS/United States ; P30 CA138313/CA/NCI NIH HHS/United States ; },
abstract = {Sensorineural hearing loss is associated with dysfunction of cochlear cells. Although immune cells play a critical role in maintaining the inner ear microenvironment, the precise immune-related molecular mechanisms underlying the pathophysiology of hearing loss remain unclear. The complement cascade contributes to the regulation of immune cell activity. Additionally, activation of the complement cascade can lead to the cellular opsonization of cells and pathogens, resulting in their engulfment and elimination by phagocytes. Complement factor B (fB) is an essential activator protein in the alternative complement pathway, and variations in the fB gene are associated with age-related macular degeneration. Here we show that mice of both sexes deficient in fB functional alleles (fB[-/-]) demonstrate progressive hearing impairment. Transcriptomic analysis of auditory nerves from adult mice detected 706 genes that were significantly differentially expressed between fB[-/-] and wild-type control animals, including genes related to the extracellular matrix and neural development processes. Additionally, a subset of differentially expressed genes was related to myelin function and neural crest development. Histological and immunohistochemical investigations revealed pathological alterations in auditory nerve myelin sheathes of fB[-/-] mice. Pathological alterations were also seen in the stria vascularis of the cochlear lateral wall in these mice. Our results implicate fB as an integral regulator of myelin maintenance and stria vascularis integrity, underscoring the importance of understanding the involvement of immune signaling pathways in sensorineural hearing loss.},
}
@article {pmid37559704,
year = {2023},
author = {Pushin, DA and Cory, DG and Kapahi, C and Kulmaganbetov, M and Mungalsingh, M and Silva, AE and Singh, T and Thompson, B and Sarenac, D},
title = {Structured light enhanced entoptic stimuli for vision science applications.},
journal = {Frontiers in neuroscience},
volume = {17},
number = {},
pages = {1232532},
pmid = {37559704},
issn = {1662-4548},
abstract = {The dichroic macular pigment in the Henle fiber layer in the fovea enables humans to perceive entoptic phenomena when viewing polarized blue light. In the standard case of linearly polarized stimuli, a faint bowtie-like pattern known as the Haidinger's brush appears in the central point of fixation. As the shape and clarity of the perceived signal is directly related to the health of the macula, Haidinger's brush has been used as a diagnostic marker in studies of early stage macular degeneration and central field visual dysfunction. However, due to the weak nature of the perceived signal the perception of the Haidinger's brush has not been integrated with modern clinical methods. Recent attempts have been made to increase the strength of the perceived signal by employing structured light with spatially varying polarization profiles. Here we review the advancements with the structured light stimuli and describe the current challenges and future prospects.},
}
@article {pmid37555645,
year = {2023},
author = {Li, Z and Duan, Y and Yan, S and Zhang, Y and Wu, Y},
title = {The miR-302/367 cluster: Aging, inflammation, and cancer.},
journal = {Cell biochemistry and function},
volume = {41},
number = {7},
pages = {752-766},
doi = {10.1002/cbf.3836},
pmid = {37555645},
issn = {1099-0844},
support = {20210302123419//ShanXi Science and Technology Department/ ; },
abstract = {MicroRNAs (miRNAs) are a class of noncoding RNAs that occupy a significant role in biological processes as important regulators of intracellular homeostasis. First, we will discuss the biological genesis and functions of the miR-302/367 cluster, including miR-302a, miR-302b, miR-302c, miR-302d, and miR-367, as well as their roles in physiologically healthy tissues. The second section of this study reviews the progress of the miR-302/367 cluster in the treatment of cancer, inflammation, and diseases associated with aging. This cluster's aberrant expression in cells and/or tissues exhibits similar or different effects in various diseases through molecular mechanisms such as proliferation, apoptosis, cycling, drug resistance, and invasion. This article also discusses the upstream and downstream regulatory networks of miR-302/367 clusters and their related mechanisms. Particularly because studies on the upstream regulatory molecules of miR-302/367 clusters, which include age-related macular degeneration, myocardial infarction, and cancer, have become more prevalent in recent years. MiR-302/367 cluster can be an important therapeutic target and the use of miRNAs in combination with other molecular markers may improve diagnostic or therapeutic capabilities, providing unique insights and a more dynamic view of various diseases. It is noted that miRNAs can be an important bio-diagnostic target and offer a promising method for illness diagnosis, prevention, and treatment.},
}
@article {pmid37553959,
year = {2023},
author = {Holzhauer, B and Adewuyi, ET},
title = {"Super-covariates": Using predicted control group outcome as a covariate in randomized clinical trials.},
journal = {Pharmaceutical statistics},
volume = {22},
number = {6},
pages = {1062-1075},
doi = {10.1002/pst.2329},
pmid = {37553959},
issn = {1539-1612},
mesh = {Humans ; Control Groups ; Bayes Theorem ; Randomized Controlled Trials as Topic ; *Research Design ; Sample Size ; Computer Simulation ; },
abstract = {The power of randomized controlled clinical trials to demonstrate the efficacy of a drug compared with a control group depends not just on how efficacious the drug is, but also on the variation in patients' outcomes. Adjusting for prognostic covariates during trial analysis can reduce this variation. For this reason, the primary statistical analysis of a clinical trial is often based on regression models that besides terms for treatment and some further terms (e.g., stratification factors used in the randomization scheme of the trial) also includes a baseline (pre-treatment) assessment of the primary outcome. We suggest to include a "super-covariate"-that is, a patient-specific prediction of the control group outcome-as a further covariate (but not as an offset). We train a prognostic model or ensembles of such models on the individual patient (or aggregate) data of other studies in similar patients, but not the new trial under analysis. This has the potential to use historical data to increase the power of clinical trials and avoids the concern of type I error inflation with Bayesian approaches, but in contrast to them has a greater benefit for larger sample sizes. It is important for prognostic models behind "super-covariates" to generalize well across different patient populations in order to similarly reduce unexplained variability whether the trial(s) to develop the model are identical to the new trial or not. In an example in neovascular age-related macular degeneration we saw efficiency gains from the use of a "super-covariate".},
}
@article {pmid37553298,
year = {2024},
author = {Britten-Jones, AC and Mack, HG and Vincent, AL and Hill, LJ and Edwards, TL and Ayton, LN},
title = {Genetic testing and gene therapy in retinal diseases: Knowledge and perceptions of optometrists in Australia and New Zealand.},
journal = {Clinical genetics},
volume = {105},
number = {1},
pages = {34-43},
pmid = {37553298},
issn = {1399-0004},
support = {//Universitas 21 Health Sciences Group International Projects Fund/ ; //University of Melbourne Early Career Researcher Grant/ ; GNT#1195713//National Health and Medical Research Council Investigator Grant/ ; //University of Melbourne Driving Research Momentum Fellowship/ ; },
mesh = {Humans ; *Optometrists ; *Optometry ; Cross-Sectional Studies ; New Zealand ; *Macular Degeneration ; Australia ; Genetic Testing ; Genetic Therapy ; },
abstract = {With advances in gene-based therapies for heritable retinal diseases, primary eye care clinicians should be informed on ocular genetics topics. This cross-sectional survey evaluated knowledge, attitudes, and concerns regarding genetic testing and gene therapy for retinal diseases among optometrists in Australia and New Zealand. Survey data included practitioner background, attitudes and practices towards genetic testing for monogenic inherited retinal disease (IRDs) and age-related macular degeneration, and knowledge of ocular genetics and gene therapy. Responses were received from 516 optometrists between 1 April and 31 December 2022. Key perceived barriers to accessing genetic testing were lack of clarity on referral pathways (81%), cost (65%), and lack of treatment options if a genetic cause is identified (50%). Almost all respondents (98%) believed that ophthalmologists should initiate genetic testing for IRDs and fewer understood the role of genetic counsellors and clinical geneticists. This study found that optometrists in Australia and New Zealand have a high level of interest in ocular genetics topics. However, knowledge gaps include referral pathways and awareness of genetic testing and gene therapy outcomes. Addressing perceived barriers to access and promoting sharing of knowledge between interdisciplinary networks can set the foundation for genetic education agendas in primary eye care.},
}
@article {pmid37552467,
year = {2023},
author = {Bansal, A and Narnaware, SH and Bawankule, PK and Gupta, R and Nagdeve, R},
title = {Retro-mode: a newer insight into dry age-related macular degeneration (AMD).},
journal = {Lasers in medical science},
volume = {38},
number = {1},
pages = {178},
pmid = {37552467},
issn = {1435-604X},
mesh = {Humans ; *Retinal Drusen/diagnostic imaging ; Cross-Sectional Studies ; Fluorescein Angiography ; Retina ; *Wet Macular Degeneration/diagnosis ; Tomography, Optical Coherence/methods ; },
abstract = {The purpose of this study is to study the role of retro-mode (RM) in early detection and to compare it with other preexisting available modalities on multimodal imaging system in dry AMD. A prospective observational cross-sectional study was done between November 2020 and October 2021 which included 409 eyes of 207 patients. For study purpose, eyes were divided into 3 groups according to the size and number of the drusen, viz, group 1: No AMD, group 2: early AMD and group 3: intermediate AMD which was further divided into 2 subgroups, viz, subgroup A: eyes with drusen size 63-125 μm and subgroup B: eyes with drusen size 125-250 μm. Patients with active or treated wet AMD, scarred choroidal neovascular membrane (CNVM), other maculopathies, other retinopathies, high myopia, trauma and glaucoma were excluded from the study. In cases of No AMD and early AMD, a number of drusens detected on RM were statistically not significant compared to fundus autofluorescence (FAF) and color photo (CF), but in intermediate AMD cases, it was statistically significant. While the area involved by drusens calculated by RM was statistically significant compared to both other modalities. When all modalities were compared with enhanced depth imaging-optical coherence tomography (EDI-OCT) at the choroid and chorio-capillary (CC) level and vessel density (VD) on optical coherence tomography angiography (OCTA) at the choroid, capillaries, deep retinal and superficial retinal plexus level; it was only RM which was found to be in sync with these proven modalities in terms of pattern and trend. In the present scenario, RM is found to be a better diagnostic modality in detecting early and a greater number of drusens with area of involvement than other existing modalities. Though superior, as found in this study, this mode cannot replace other modalities at present but only acts as a complementary investigation in early detection of this disease.},
}
@article {pmid37552202,
year = {2023},
author = {Inam, O and Kaplan, HJ and Tezel, TH},
title = {Retinal Hydration Assessment With Optical Coherence Tomography: Unraveling Its Significance in Retinal Fluid Dynamics, Macular Edema and Cell Viability.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {8},
pages = {4},
pmid = {37552202},
issn = {2164-2591},
mesh = {Humans ; *Macular Edema/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Diabetic Retinopathy/diagnostic imaging ; Cell Survival ; Hydrodynamics ; Retina/diagnostic imaging ; },
abstract = {PURPOSE: The purpose of this study was to quantify retinal hydration (RH) levels with optical coherence tomography (OCT) and determine the extent of cellular damage resulting from intraretinal fluid alterations.<br><br>METHODS: We took 6.0 mm sections of the human sensory retina that were excised from 18 fresh (<24 hours) donor eyes. They were either exposed to various osmotic stresses between 90 and 305 mOsm or dehydrated under a laminar flow hood. Change in tissue weight was used to calculate the retinal water content (RWC). Image analyses were conducted on OCT between 0 and 180 minutes to assess retinal thickness (RT) and "optically empty areas" (OEAs) representing intraretinal fluid. Correlations were sought among RWC, OEA, RWC, and RT. The effect of RH on retinal cell viability (RCV) was assessed with the Live-Dead Assay.<br><br>RESULTS: RH demonstrated a stronger correlation with the OEA than plain RT measurements (r = 0.99, P < 0.001). RH-RCV interaction fits well to a bell-shaped curve. A significant proportion of retinal cells (>80%) remained viable despite the change in RH ranging between 0.87 and 1.42 times. This "safe zone" was found to be associated with a 22% increase in OEA (r = 0.99, P < 0.01).<br><br>CONCLUSIONS: OCT has been demonstrated as a valuable tool for assessing RH and can be used for intraretinal fluid content analysis. RH is a better indicator of RCV compared with RT. Computing RH may improve the determination of functional outcome of intravitreal pharmacotherapeutics used for diabetic macular edema and exudative age-related macular degeneration.<br><br>TRANSLATIONAL RELEVANCE: We link basic research and clinical care by assessing retinal hydration's impact on retinal fluid dynamics, macular edema, and cell viability.},
}
@article {pmid37551274,
year = {2023},
author = {Cao, J and Zhang, F and Xiong, W},
title = {Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology.},
journal = {International journal of nanomedicine},
volume = {18},
number = {},
pages = {4421-4430},
pmid = {37551274},
issn = {1178-2013},
mesh = {Humans ; Vascular Endothelial Growth Factor A ; *Ophthalmology ; *Macular Degeneration ; *Aptamers, Nucleotide/therapeutic use/pharmacology ; *Diabetic Retinopathy/drug therapy ; *Glaucoma/drug therapy ; Acceleration ; },
abstract = {Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-β receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.},
}
@article {pmid37550000,
year = {2023},
author = {Wang, Y and Liu, Y and Wang, Y and Wu, Y and Chen, Z and Wang, F and Wan, X and Wang, F and Sun, X},
title = {Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degeneration.},
journal = {Life science alliance},
volume = {6},
number = {11},
pages = {},
pmid = {37550000},
issn = {2575-1077},
mesh = {Humans ; Angiogenesis Inhibitors/metabolism/therapeutic use ; Cholesterol/metabolism ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Macrophages/metabolism ; Sterols/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Visual Acuity ; *Wet Macular Degeneration/metabolism ; *Sulfotransferases/metabolism ; },
abstract = {Disordered immune responses and cholesterol metabolism have been implicated in age-related macular degeneration (AMD), the leading cause of blindness in elderly individuals. SULT2B1, the key enzyme of sterol sulfonation, plays important roles in inflammation and cholesterol metabolism. However, the role and underlying mechanism of SULT2B1 in AMD have not been investigated thus far. Here, we report that SULT2B1 is specifically expressed in macrophages in choroidal neovascularization lesions. Sutl2b1 deficiency significantly reduced leakage areas and inhibited pathological angiogenesis by inhibiting M2 macrophage activation in vivo and in vitro. Mechanistically, loss of Sult2b1 activated LXRs and subsequently increased ABCA1 and ABCG1 (ABCA1/G1)-mediated cholesterol efflux from M2 macrophages. LXR inhibition (GSK2033 treatment) in Sult2b1 [-/-] macrophages reversed M2 polarization and decreased intracellular cholesterol capacity to promote pathological angiogenesis. In contrast to SULT2B1, STS, an enzyme of sterol desulfonation, protected against choroidal neovascularization development by activating LXR-ABCA1/G1 signalling to block M2 polarization. Collectively, these data reveal a cholesterol metabolism axis related to macrophage polarization in neovascular AMD.},
}
@article {pmid37549871,
year = {2023},
author = {Tan, Y and Huang, J and Li, D and Zou, C and Liu, D and Qin, B},
title = {Single-cell RNA sequencing in dissecting microenvironment of age-related macular degeneration: Challenges and perspectives.},
journal = {Ageing research reviews},
volume = {90},
number = {},
pages = {102030},
doi = {10.1016/j.arr.2023.102030},
pmid = {37549871},
issn = {1872-9649},
mesh = {Humans ; *Macular Degeneration/metabolism ; Sequence Analysis, RNA ; Biomarkers ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 years, yet its etiology and pathogenesis largely remain uncovered. Single-cell RNA sequencing (scRNA-seq) technologies are recently developed and have a number of advantages over conventional bulk RNA sequencing techniques in uncovering the heterogeneity of complex microenvironments containing numerous cell types and cell communications during various biological processes. In this review, we summarize the latest discovered cellular components and regulatory mechanisms during AMD development revealed by scRNA-seq. In addition, we discuss the main challenges and future directions in exploring the pathophysiology of AMD equipped with single-cell technologies. Our review underscores the importance of multimodal single-cell platforms (such as single-cell spatiotemporal multi-omics and single-cell exosome omics) as new approaches for basic and clinical AMD research in identifying biomarker, characterizing cellular responses to drug treatment and environmental stimulation.},
}
@article {pmid37549082,
year = {2024},
author = {Zhao, P and Song, X and Xi, X and Nie, X and Meng, X and Qu, Y and Yin, Y},
title = {Biomarkers-Aware Asymmetric Bibranch GAN With Adaptive Memory Batch Normalization for Prediction of Anti-VEGF Treatment Response in Neovascular Age-Related Macular Degeneration.},
journal = {IEEE journal of biomedical and health informatics},
volume = {28},
number = {1},
pages = {557-568},
doi = {10.1109/JBHI.2023.3302989},
pmid = {37549082},
issn = {2168-2208},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/diagnostic imaging/drug therapy ; Biomarkers/analysis ; *Angiogenesis Inhibitors/therapeutic use ; *Image Interpretation, Computer-Assisted/methods ; Neural Networks, Computer ; },
abstract = {The emergence of anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized neovascular age-related macular degeneration (nAMD). Post-therapeutic optical coherence tomography (OCT) imaging facilitates the prediction of therapeutic response to anti-VEGF therapy for nAMD. Although the generative adversarial network (GAN) is a popular generative model for post-therapeutic OCT image generation, it is realistically challenging to gather sufficient pre- and post-therapeutic OCT image pairs, resulting in overfitting. Moreover, the available GAN-based methods ignore local details, such as the biomarkers that are essential for nAMD treatment. To address these issues, a Biomarkers-aware Asymmetric Bibranch GAN (BAABGAN) is proposed to efficiently generate post-therapeutic OCT images. Specifically, one branch is developed to learn prior knowledge with a high degree of transferability from large-scale data, termed the source branch. Then, the source branch transfer knowledge to another branch, which is trained on small-scale paired data, termed the target branch. To boost the transferability, a novel Adaptive Memory Batch Normalization (AMBN) is introduced in the source branch, which learns more effective global knowledge that is impervious to noise via memory mechanism. Also, a novel Adaptive Biomarkers-aware Attention (ABA) module is proposed to encode biomarkers information into latent features of target branches to learn finer local details of biomarkers. The proposed method outperforms traditional GAN models and can produce high-quality post-treatment OCT pictures with limited data sets, as shown by the results of experiments.},
}
@article {pmid37547613,
year = {2023},
author = {Hu, M and Wu, B and Lu, D and Xie, J and Chen, Y and Yang, Z and Dai, W},
title = {Two-step hierarchical neural network for classification of dry age-related macular degeneration using optical coherence tomography images.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1221453},
pmid = {37547613},
issn = {2296-858X},
abstract = {PURPOSE: The aim of this study is to apply deep learning techniques for the development and validation of a system that categorizes various phases of dry age-related macular degeneration (AMD), including nascent geographic atrophy (nGA), through the analysis of optical coherence tomography (OCT) images.<br><br>METHODS: A total of 3,401 OCT macular images obtained from 338 patients admitted to Shenyang Aier Eye Hospital in 2019-2021 were collected for the development of the classification model. We adopted a convolutional neural network (CNN) model and introduced hierarchical structure along with image enhancement techniques to train a two-step CNN model to detect and classify normal and three phases of dry AMD: atrophy-associated drusen regression, nGA, and geographic atrophy (GA). Five-fold cross-validation was used to evaluate the performance of the multi-label classification model.<br><br>RESULTS: Experimental results obtained from five-fold cross-validation with different dry AMD classification models show that the proposed two-step hierarchical model with image enhancement achieves the best classification performance, with a f1-score of 91.32% and a kappa coefficients of 96.09% compared to the state-of-the-art models. The results obtained from the ablation study demonstrate that the proposed method not only improves accuracy across all categories in comparison to a traditional flat CNN model, but also substantially enhances the classification performance of nGA, with an improvement from 66.79 to 81.65%.<br><br>CONCLUSION: This study introduces a novel two-step hierarchical deep learning approach in categorizing dry AMD progression phases, and demonstrates its efficacy. The high classification performance suggests its potential for guiding individualized treatment plans for patients with macular degeneration.},
}
@article {pmid37547172,
year = {2023},
author = {Rush, RB},
title = {One-Year Outcomes of Faricimab Treatment for Aflibercept-Resistant Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {2201-2208},
pmid = {37547172},
issn = {1177-5467},
abstract = {PURPOSE: To assess the 12-month outcomes of intravitreal faricimab (IVF) in treatment-resistant neovascular age-related macular degeneration (nAMD) subjects recalcitrant to intravitreal aflibercept (IVA).<br><br>METHODS: This study was conducted as a retrospective interventional case series of nAMD patients receiving treatment at a single private practice institution. All included patients at baseline had undergone six or more IVA injections over the previous 12 months, four or more IVA injections over the previous 6 months, had a central macular thickness (CMT) &#x2265;320 &#xb5;m on optical coherence tomography (OCT), and were observed to have intraretinal and/or subretinal fluid on OCT assessment. The baseline exam for the purpose of this study was considered the visit in which the patient was switched from IVA to IVF. Patients were managed with a real-world treat-and-extend protocol and followed over a 12-month study period.<br><br>RESULTS: A total of 54 eyes of 54 subjects were analyzed. Overall, 31.5% (17/54) of subjects attained a treatment interval &#x2265;8 weeks and had a fluid-free macula on OCT at 12 months. The CMT on OCT decreased from 395.4 (383.5-407.3) &#xb5;m at baseline to 350.0 (335.1-364.8) &#xb5;m at the end of the 12-month study interval (p<0.01). There were 16.7% (9/54) of subjects who gained three or more lines of Snellen visual acuity at the end of the study. Visual acuity improved from 0.72 (0.67-0.77) logMAR (Snellen 20/105) at baseline to 0.59 (0.55-0.64) logMAR (Snellen 20/78) at the end of the study (p<0.01).<br><br>CONCLUSION: A clinically significant minority of aflibercept-resistant nAMD subjects may attain longer treatment intervals and improved outcomes at 12 months after switching to IVF when a treat-and-extend treatment protocol is utilized. IVF use may be considered whenever resistance to IVA is encountered in this patient population.},
}
@article {pmid37544613,
year = {2024},
author = {Heath Jeffery, RC and Chen, FK},
title = {Macular neovascularization in inherited retinal diseases: A review.},
journal = {Survey of ophthalmology},
volume = {69},
number = {1},
pages = {1-23},
doi = {10.1016/j.survophthal.2023.07.007},
pmid = {37544613},
issn = {1879-3304},
support = {NT1116360 (FKC), GNT1188694 (FKC), GNT1054712 (FKC), AND MRF1142962//Medical Research Council of Australia/ ; MRF1142962//McCusker Foundation/ ; },
mesh = {Adult ; Humans ; Endothelial Growth Factors ; Retina ; *Macular Degeneration/complications/diagnosis ; *Retinal Degeneration/complications ; Neovascularization, Pathologic ; Fluorescein Angiography ; Tomography, Optical Coherence ; *Choroidal Neovascularization ; Retrospective Studies ; *Retinal Neovascularization/complications ; },
abstract = {Inherited retinal diseases (IRDs) are the most common cause of blindness in working-age adults. Macular neovascularization (MNV) may be a presenting feature or occurs as a late-stage complication in several IRDs. We performed an extensive literature review on MNV associated with IRDs. MNV is a well-known complication of Sorsby fundus dystrophy and pseudoxanthoma elasticum. Those with late-onset Stargardt disease may masquerade as exudative age-related macular degeneration (AMD) when MNV is the presenting feature. Peripherinopathies may develop MNV that responds well to a short course of anti-vascular endothelial growth factor (anti-VEGF) therapy, while bestrophinopathies tend to develop MNV in the early stages of the disease without vision loss. Enhanced S-cone syndrome manifests type 3 MNV that typically regresses into a subfoveal fibrotic nodule. MNV is only a rare complication in choroideraemia and rod-cone dystrophies. Most IRD-related MNVs exhibit a favorable visual prognosis requiring less intensive regimens of anti-vascular endothelial growth factor therapy compared to age-related macular degeneration. We discuss the role of key imaging modalities in the diagnosis of MNV across a wide spectrum of IRDs and highlight the gaps in our knowledge with respect to the natural history and prognosis to pave the way for future directions of research.},
}
@article {pmid37542615,
year = {2023},
author = {Sacconi, R and Tombolini, B and Zucchiatti, I and Servillo, A and Menean, M and Alessandrini, GF and Querques, L and Prascina, F and Charbel Issa, P and Bandello, F and Querques, G},
title = {Subclinical Angioid Streaks with Pseudodrusen: A New Phenotype of Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2729-2743},
pmid = {37542615},
issn = {2193-8245},
abstract = {INTRODUCTION: To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS.<br><br>METHODS: This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch's membrane (BM) breaks and large BM dehiscences.<br><br>RESULTS: Among 543 eyes of 274 patients with AMD (mean &#xb1; standard deviation: 82&#x2009;&#xb1;&#x2009;7&#xa0;years), 73 eyes of 46 patients (81&#x2009;&#xb1;&#x2009;7&#xa0;years; p&#x2009;=&#x2009;0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3-16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a "petaloid-like" pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P&#x2009;<&#x2009;0.001). Among the 73 subclinical AS cases, 71 were affected by late AMD (57 with macular neovascularization, 14 with geographic atrophy), showing a more advanced AMD stage in comparison with AMD eyes without subclinical AS (P&#x2009;<&#x2009;0.001). The following OCT features were disclosed: BM breaks in 100% of cases and BM dehiscences in 37%.<br><br>CONCLUSIONS: Subclinical AS in eyes with AMD is a peculiar phenotype of the disease, with features suggesting a primary involvement of Bruch's membrane and clinical similarities with mild, late-onset pseudoxanthoma elasticum.},
}
@article {pmid37540459,
year = {2023},
author = {Liu, S and Zhang, W},
title = {NAD[+] metabolism and eye diseases: current status and future directions.},
journal = {Molecular biology reports},
volume = {50},
number = {10},
pages = {8653-8663},
pmid = {37540459},
issn = {1573-4978},
support = {82060180//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *NAD/metabolism ; Quality of Life ; Eye/metabolism ; *Macular Degeneration/metabolism ; Aging/metabolism ; },
abstract = {Currently, there are no truly effective treatments for a variety of eye diseases, such as glaucoma, age-related macular degeneration (AMD), and inherited retinal degenerations (IRDs). These conditions have a significant impact on patients' quality of life and can be a burden on society. However, these diseases share a common pathological process of NAD[+] metabolism disorders. They are either associated with genetically induced primary NAD[+] synthase deficiency, decreased NAD[+] levels due to aging, or enhanced NAD[+] consuming enzyme activity during disease pathology. In this discussion, we explore the role of NAD[+] metabolic disorders in the development of associated ocular diseases and the potential advantages and disadvantages of various methods to increase NAD[+] levels. It is essential to carefully evaluate the possible adverse effects of these methods and conduct a more comprehensive and objective assessment of their function before considering their use.},
}
@article {pmid37540261,
year = {2024},
author = {Wang, JD and Liu, MR and Liu, ML and Zhang, R and Chen, CX and Cao, K},
title = {An auxiliary diagnostic tool for common fundus diseases based on fundus color photography and light-weight classification models.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {1},
pages = {223-229},
pmid = {37540261},
issn = {1435-702X},
mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; Diagnostic Techniques, Ophthalmological ; Fundus Oculi ; *Glaucoma/diagnosis ; *Macular Degeneration/diagnosis ; Photography ; *Myopia ; },
abstract = {OBJECTIVE: To evaluate the performance of two lightweight neural network models in the diagnosis of common fundus diseases and make comparison to another two classical models.<br><br>METHODS: A total of 16,000 color fundus photography were collected, including 2000 each of glaucoma, diabetic retinopathy (DR), high myopia, central retinal vein occlusion (CRVO), age-related macular degeneration (AMD), optic neuropathy, and central serous chorioretinopathy (CSC), in addition to 2000 normal fundus. Fundus photography was obtained from patients or physical examiners who visited the Ophthalmology Department of Beijing Tongren Hospital, Capital Medical University. Each fundus photography has been diagnosed and labeled by two professional ophthalmologists. Two classical classification models (ResNet152 and DenseNet121), and two lightweight classification models (MobileNetV3 and ShufflenetV2), were trained. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate the performance of the four models.<br><br>RESULTS: Compared with the classical classification model, the total size and number of parameters of the two lightweight classification models were significantly reduced, and the classification speed was sharply improved. Compared with the DenseNet121 model, the ShufflenetV2 model took 50.7% less time to make a diagnosis on a fundus photography. The classical models performed better than lightweight classification models, and Densenet121 showed highest AUC in five out of the seven common fundus diseases. However, the performance of lightweight classification models is satisfying. The AUCs using MobileNetV3 model to diagnose AMD, diabetic retinopathy, glaucoma, CRVO, high myopia, optic atrophy, and CSC were 0.805, 0.892, 0.866, 0.812, 0.887, 0.868, and 0.803, respectively. For ShufflenetV2model, the AUCs for the above seven diseases were 0.856, 0.893, 0.855, 0.884, 0.891, 0.867, and 0.844, respectively.<br><br>CONCLUSION: The training of light-weight neural network models based on color fundus photography for the diagnosis of common fundus diseases is not only fast but also has a significant reduction in storage size and parameter number compared with the classical classification model, and can achieve satisfactory accuracy.},
}
@article {pmid37539829,
year = {2023},
author = {Berlin, A and Matney, E and Jones, SG and Clark, ME and Swain, TA and McGwin, G and Martindale, RM and Sloan, KR and Owsley, C and Curcio, CA},
title = {Discernibility of the Interdigitation Zone (IZ), a Potential Optical Coherence Tomography (OCT) Biomarker for Visual Dysfunction in Aging.},
journal = {Current eye research},
volume = {48},
number = {11},
pages = {1050-1056},
pmid = {37539829},
issn = {1460-2202},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; *Aging/physiology ; Male ; Female ; Adult ; Middle Aged ; Young Adult ; Aged ; *Dark Adaptation/physiology ; *Visual Acuity/physiology ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; Vision Disorders/physiopathology/diagnosis ; Biomarkers ; },
abstract = {PURPOSE: Photoreceptor (PR) outer segments, retinal pigment epithelium apical processes, and inter-PR matrix contribute to the interdigitation zone (IZ) of optical coherence tomography (OCT). We hypothesize that this interface degrades over adulthood, in concert with a delay of rod mediated dark adaptation (RMDA). To explore this idea, we determined IZ discernibility and RMDA in younger and older adults.<br><br>METHODS: For this cross-sectional study, eyes of 20 young (20-30&#x2009;years) and 40 older (&#x2265;60&#x2009;years) participants with normal maculas according to the AREDS 9-step grading system underwent OCT imaging and RMDA testing at 5&#xb0; superior to the fovea. Custom FIJI plugins enabled analysis for IZ discernibility at 9 eccentricities in 0.5&#x2009;mm steps on one single horizontal B-scan through the fovea. Locations with discernible IZ met two criteria: visibility on B-scans and a distinct peak on a longitudinal reflectivity profile. The frequency of sites meeting both criteria was compared between both age groups and correlated with rod intercept time (RIT).<br><br>RESULTS: The median number of locations with discernible IZ was significantly higher (foveal, 4 vs. 0, p&#x2009;=&#x2009;0.0099; extra-foveal 6 vs. 0, p&#x2009;<&#x2009;0.001) in eyes of young (26&#x2009;&#xb1;&#x2009;3&#x2009;years) compared to older (73&#x2009;&#xb1;&#x2009;5&#x2009;years) participants. For the combined young and older sample, the higher frequency of discernible IZ was correlated with shorter RIT (faster dark adaptation) (rs&#xa0;=&#xa0;-0.56, p&#x2009;<&#x2009;0.0001). This association was significant within young eyes (rs&#xa0;=&#xa0;-0.54; p&#xa0;=&#xa0;0.0134) and not within older eyes (rs&#xa0;=&#xa0;-0.29, p&#x2009;=&#x2009;0.706).<br><br>CONCLUSIONS: Results suggest that the interface between outer segments and apical processes degrades in normal aging, potentially contributing to delayed rod-mediated dark adaptation. More research is needed to verify an age-related association between IZ discernibility and rod-mediated dark adaptation. If confirmed in a large sample, IZ discernibility might prove to be a valuable biomarker and predictor for visual function in aging.},
}
@article {pmid37537388,
year = {2024},
author = {Iglicki, M and Khoury, M and Donato, L and Quispe, DJ and Negri, HP and Melamud, JI},
title = {Comparison of subretinal aflibercept vs ranibizumab vs bevacizumab in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA in naïve submacular haemorrhage secondary to nAMD. "The Submarine Study".},
journal = {Eye (London, England)},
volume = {38},
number = {2},
pages = {292-296},
pmid = {37537388},
issn = {1476-5454},
mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; Male ; *Ranibizumab/therapeutic use ; Bevacizumab/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Cohort Studies ; Treatment Outcome ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Retinal Hemorrhage/drug therapy/etiology ; Intravitreal Injections ; },
abstract = {OBJECTIVE: To compare efficacy and safety profile of subretinal aflibercept, ranibizumab, and bevacizumab in the context of pars plana vitrectomy, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage (SMH) due to naïve neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective interventional cohort study.<br><br>PARTICIPANTS: 123 eyes of 123 patients treated with subretinal aflibercept (n&#x2009;=&#x2009;41, 33%), ranibizumab (n&#x2009;=&#x2009;41,33%), and bevacizumab (n&#x2009;=&#x2009;41, 33%).<br><br>METHODS: Review of electronic medical records for best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) at baseline and 24 months after treatment.<br><br>MAIN OUTCOME MEASURES: BCVA, CST, and number of intravitreal anti VEGF over 24 months.<br><br>RESULTS: Mean age of patients was 80.5&#x2009;&#xb1;&#x2009;5.5 years, 43.9% were female. Mean time from symptom onset until surgery was 1.1 days (range 0-3 days). In all cases, the SMH did not reach the arcades. CST at baseline was 627&#x2009;&#xb1;&#x2009;140&#x2009;&#xb5;, 739&#x2009;&#xb1;&#x2009;54&#x2009;&#xb5;, and 793&#x2009;&#xb1;&#x2009;93&#x2009;&#xb5; (p&#x2009;=&#x2009;0.0001) for aflibercept, ranibizumab, or bevacizumab, respectively. Baseline BCVA (logMAR) was 0.65&#x2009;&#xb1;&#x2009;0.13, 0.69&#x2009;&#xb1;&#x2009;0.96, and 0.74&#x2009;&#xb1;&#x2009;0.81 (p&#x2009;=&#x2009;0.0041) for aflibercept, ranibizumab, and bevacizumab, respectively. All three groups showed statistically significant improvement in BCVA and CST (for all groups: p&#x2009;<&#x2009;0.001). There was no statistically significant difference at the final BCVA (p&#x2009;=&#x2009;0.789). The mean number of anti VEGF given during follow-up period was 5.2&#x2009;&#xb1;&#x2009;0.81, 4.4&#x2009;&#xb1;&#x2009;0.63, and 5.5&#x2009;&#xb1;&#x2009;0.95 (p&#x2009;=&#x2009;0.0001) for aflibercept, ranibizumab, and bevacizumab, respectively.<br><br>CONCLUSION: This study shows that aflibercept, ranibizumab, and bevacizumab in a subretinal manner in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage secondary to na&#xef;ve nAMD work with the same efficacy and safety profile.},
}
@article {pmid37536385,
year = {2023},
author = {Liu, D and Zhang, C and Zhang, J and Xu, GT and Zhang, J},
title = {Molecular pathogenesis of subretinal fibrosis in neovascular AMD focusing on epithelial-mesenchymal transformation of retinal pigment epithelium.},
journal = {Neurobiology of disease},
volume = {185},
number = {},
pages = {106250},
doi = {10.1016/j.nbd.2023.106250},
pmid = {37536385},
issn = {1095-953X},
mesh = {Humans ; Aged ; *Retinal Pigment Epithelium/metabolism/pathology ; Angiogenesis Inhibitors/metabolism/therapeutic use ; Epithelial-Mesenchymal Transition ; Vascular Endothelial Growth Factor A/metabolism ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/metabolism/pathology ; Fibrosis ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss among elderly people in developed countries. Neovascular AMD (nAMD) accounts for more than 90% of AMD-related vision loss. At present, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is widely used as the first-line therapy to decrease the choroidal and retinal neovascularizations, and thus to improve or maintain the visual acuity of the patients with nAMD. However, about 1/3 patients still progress to irreversible visual impairment due to subretinal fibrosis even with adequate anti-VEGF treatment. Extensive literatures support the critical role of epithelial-mesenchymal transformation (EMT) of retinal pigment epithelium (RPE) in the pathogenesis of subretinal fibrosis in nAMD, but the underlying mechanisms still remain largely unknown. This review summarized the molecular pathogenesis of subretinal fibrosis in nAMD, especially focusing on the transforming growth factor-β (TGF-β)-induced EMT pathways. It was also discussed how these pathways crosstalk and respond to signals from the microenvironment to mediate EMT and contribute to the progression of nAMD-related subretinal fibrosis. Targeting EMT signaling pathways might provide a promising and effective therapeutic strategy to treat subretinal fibrosis secondary to nAMD.},
}
@article {pmid37535382,
year = {2023},
author = {Wykoff, CC and Brown, DM and Reed, K and Berliner, AJ and Gerstenblith, AT and Breazna, A and Abraham, P and Fein, JG and Chu, KW and Clark, WL and Leal, S and Schmelter, T and Hirshberg, B and Yancopoulos, GD and Vitti, R and , },
title = {Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration: The Phase 2 CANDELA Randomized Clinical Trial.},
journal = {JAMA ophthalmology},
volume = {141},
number = {9},
pages = {834-842},
pmid = {37535382},
issn = {2168-6173},
mesh = {Humans ; Female ; Male ; Angiogenesis Inhibitors/therapeutic use ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/adverse effects ; },
abstract = {IMPORTANCE: Aflibercept, 8 mg, may have greater therapeutic benefits compared with aflibercept, 2 mg, in patients with neovascular age-related macular degeneration (nAMD), including potentially improved outcomes and decreased treatment burden.<br><br>OBJECTIVE: To assess safety and efficacy of aflibercept, 8 mg, in patients with nAMD.<br><br>The CANDELA trial was a phase 2, randomized, single-masked, open-label, 44-week clinical trial conducted in the US. Treatment-naive patients with active subfoveal choroidal neovascularization secondary to nAMD and a best-corrected visual acuity score of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled between November 2019 and November 2021.<br><br>INTERVENTIONS: Eligible participants were randomized 1:1 to receive 3 monthly doses of 8 mg (70 &#x3bc;L) or 2 mg (50 &#x3bc;L) of aflibercept followed by doses at weeks 20 and 32.<br><br>MAIN OUTCOMES AND MEASURES: Coprimary end points were the proportion of eyes without fluid (absence of intraretinal and subretinal fluid) in the central subfield at week 16 and safety.<br><br>RESULTS: All 106 eligible eyes were randomized to receive aflibercept, 8 mg (n&#x2009;=&#x2009;53), or aflibercept, 2 mg (n&#x2009;=&#x2009;53). Overall, 66 participants (62.3%) were female. The proportion of eyes without fluid in the central subfield with 8-mg vs 2-mg aflibercept was 50.9% (n&#x2009;=&#x2009;27) vs 34.0% (n&#x2009;=&#x2009;18) (difference, 17.0 [95% CI, -1.6 to 35.5] percentage points; P&#x2009;=&#x2009;.08) at week 16 and 39.6% (n&#x2009;=&#x2009;21) vs 28.3% (n&#x2009;=&#x2009;15) (difference, 11.3 [95% CI, -6.6 to 29.2] percentage points; nominal P&#x2009;=&#x2009;.22) at week 44. At week 44, mean (SE) change in central retinal thickness was -159.4 (16.4) vs -137.2 (22.8) &#x3bc;m with 8 mg vs 2 mg of aflibercept, respectively (least squares mean difference, -9.5 [95% CI, -51.4 to 32.4]; nominal P&#x2009;=&#x2009;.65) and mean (SE) change in best-corrected visual acuity score was +7.9 (1.5) vs +5.1 (1.5) letters (least squares mean difference, +2.8 [95% CI, -1.4 to +7.0]; nominal P&#x2009;=&#x2009;.20). No differences in safety profiles between the groups were observed.<br><br>CONCLUSIONS AND RELEVANCE: Although aflibercept, 8 mg, did not achieve the primary efficacy end point at week 16 at the 2-sided significance level of 5%, the observed trends in anatomic and visual improvements over 44 weeks with aflibercept, 8 mg, indicate potential additional therapeutic benefit over aflibercept, 2 mg. No new safety signals were observed over 44 weeks. These findings support further evaluation of aflibercept, 8 mg, in pivotal trials of exudative retinal diseases including nAMD and diabetic macular edema.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04126317.},
}
@article {pmid37532290,
year = {2024},
author = {Lam, S and Lindsey, J and Carranza Leon, BG and Takkouche, S},
title = {Shedding light on eye disease in obesity: A review.},
journal = {Clinical obesity},
volume = {14},
number = {1},
pages = {e12616},
doi = {10.1111/cob.12616},
pmid = {37532290},
issn = {1758-8111},
mesh = {Humans ; *Cataract/complications ; *Glaucoma/complications ; *Diabetic Retinopathy/complications ; *Macular Degeneration/complications ; Obesity/complications ; },
abstract = {Obesity is known to be associated with numerous ocular manifestations, including but not limited to, diabetic retinopathy (DR), age-related macular degeneration (AMD), cataracts, glaucoma, and dry eye disease. This review aims to provide an overview of the ophthalmological findings in obesity. A literature search was conducted using PubMed and Cochrane databases for studies describing randomized clinical trials, meta-analyses, systematic reviews, and observational studies published from 1 January 2017 to 1 April 2023. The search terms used included relevant keywords such as 'obesity', 'body mass index', 'waist-to-hip ratio', 'bariatric', 'ophthalmology', 'eye disease', 'myopia', 'retinopathy', 'glaucoma', and 'cataract'. This literature search was performed on 1 April 2023. Obesity is associated with increased risk of developing DR, a sight-threatening complication of diabetes mellitus. Similarly, obesity has been shown to increase risk of AMD, cataracts, glaucoma, and ocular surface disease. Multiple mechanisms linking obesity to ophthalmic disease have been proposed. Adipose tissue produces various inflammatory cytokines that can affect ocular tissues, leading to disease progression. Additionally, obesity is associated with systemic metabolic changes that can influence ocular health. Bariatric surgery has been shown to be protective against development of ophthalmic disease. Obesity is a significant risk factor for several ophthalmological diseases. Healthcare providers should encourage weight loss in patients with overweight or obesity to prevent or delay the onset of ocular complications. Further research is needed to better understand the underlying mechanisms of this association, and to identify effective strategies for preventing or managing ophthalmic disease in patients with obesity.},
}
@article {pmid37532148,
year = {2023},
author = {Qi, Q and Wei, Y and Zhang, X and Guan, J and Mao, S},
title = {Challenges and strategies for ocular posterior diseases therapy via non-invasive advanced drug delivery.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {361},
number = {},
pages = {191-211},
doi = {10.1016/j.jconrel.2023.07.055},
pmid = {37532148},
issn = {1873-4995},
mesh = {Humans ; Quality of Life ; Drug Delivery Systems ; Eye ; *Eye Diseases/drug therapy ; *Diabetic Retinopathy/drug therapy ; },
abstract = {Posterior segment diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vital factor that seriously threatens human vision health and quality of life, the treatment of which poses a great challenge to ophthalmologists and ophthalmic scientists. In particular, ocular posterior drug delivery in a non-invasive manner is highly desired but still faces many difficulties such as rapid drug clearance, limited permeability and low drug accumulation at the target site. At present, many novel non-invasive topical ocular drug delivery systems are under development aiming to improve drug delivery efficiency and biocompatibility for better therapy of posterior segment oculopathy. The purpose of this review is to present the challenges in the noninvasive treatment of posterior segment diseases, and to propose strategies to tackle these bottlenecks. First of all, barriers to ocular administration were introduced based on ocular physiological structure and behavior, including analysis and discussion on the influence of ocular structures on noninvasive posterior segment delivery. Thereafter, various routes of posterior drug delivery, both invasive and noninvasive, were illustrated, along with the respective anatomical obstacles that need to be overcome. The widespread and risky application of invasive drug delivery, and the need to develop non-invasive local drug delivery with alternative to injectable therapy were described. Absorption routes through topical administration and strategies to enhance ocular posterior drug delivery were then discussed. As a follow-up, an up-to-date research advances in non-invasive delivery systems for the therapy of ocular fundus lesions were presented, including different nanocarriers, contact lenses, and several other carriers. In conclusion, it seems feasible and promising to treat posterior oculopathy via non-invasive local preparations or in combination with appropriate devices.},
}
@article {pmid37531162,
year = {2023},
author = {Xu, ZH and Zhang, H and Zhang, CJ and Yu, SJ and Yuan, J and Jin, K and Jin, ZB},
title = {REG1A protects retinal photoreceptors from blue light damage.},
journal = {Annals of the New York Academy of Sciences},
volume = {1527},
number = {1},
pages = {60-74},
doi = {10.1111/nyas.15045},
pmid = {37531162},
issn = {1749-6632},
mesh = {Humans ; *Retina/metabolism ; *Retinal Degeneration/prevention &amp; control/metabolism ; Photoreceptor Cells, Vertebrate/metabolism ; Apoptosis ; Light ; Lithostathine ; },
abstract = {With the increased use of artificial light and the prolonged use of optoelectronic products, light damage (LD) to the human retina has been identified as a global vision-threatening problem. While there is evidence of a significant correlation between light-induced retinal damage and age-related vision impairment in age-related macular degeneration, it is unclear how light-induced retinal degeneration manifests itself and whether there are agents capable of preventing the development of LD in the retina. This study investigated a mechanism by which blue light leads to photoreceptor death. By observing blue light exposure in retinal organoids and photoreceptor cells, we concluded that there could be significant apoptosis of the photoreceptors. We demonstrate that regenerating islet-derived 1 alpha (REG1A) prevents photoreceptors from undergoing this LD-induced apoptosis by increasing expression of the anti-apoptotic gene Bcl2 and downregulating expression of the pro-apoptotic gene Bax, resulting in reduced mitochondrial damage and improved aerobic capacity in photoreceptor cells. For the first time, REG1A has been shown to restore mitochondrial function and cell apoptosis after LD-induced damage, suggesting its potential application in the prevention and treatment of retinal vision loss.},
}
@article {pmid37531133,
year = {2023},
author = {Özer Özcan, Z and Gürbostan Soysal, G and Tıskaoğlu, NS and Berhuni, M},
title = {The effect of baseline intraocular pressure and anterior segment parameters on intraocular pressure after intravitreal bevacizumab injection.},
journal = {Cutaneous and ocular toxicology},
volume = {42},
number = {4},
pages = {248-252},
doi = {10.1080/15569527.2023.2243505},
pmid = {37531133},
issn = {1556-9535},
mesh = {Humans ; Bevacizumab/adverse effects ; *Intraocular Pressure ; Angiogenesis Inhibitors/adverse effects ; Retrospective Studies ; Cross-Sectional Studies ; Intravitreal Injections ; *Eye Diseases/chemically induced ; },
abstract = {PURPOSE: We aimed to compare the predictive effect of pre-injection intraocular pressure (IOP) and anterior segment parameters on post-injection IOP values after intravitreal bevacizumab injection for neovascular age-related macular degeneration (NVAMD) in phakic and pseudophakic patient groups.<br><br>MATERIAL AND METHODS: This retrospective cross-sectional study included 65 eyes of 65 treatment-naive NVAMD patients. Patients were divided into two groups according to their lens status (35 phakic and 30 pseudophakic patients). Pre-injection IOP, anterior segment parameters measured with PENTACAM, and post-injection IOP values measured at the 5th minute were recorded. Univariate and multivariate regression analyses were used to recognise the predictive effect of pre-injection IOP and anterior segment parameters on post-injection IOP for each group.<br><br>RESULTS: Multivariate regression analyses showed that the decrease in anterior chamber depth (ACD), and the increase in pre-injection IOP were significantly correlated with higher post-injection IOP in the phakic patient group (p&#x2009;=&#x2009;0.019 and 0.031; respectively). No correlation was found in the pseudophakic patient group.<br><br>CONCLUSION: Pre-injection ACD and IOP values may be predictive of higher post-injection IOP in phakic patients. Preoperative assessment of these parameters could be beneficial in patients at risk of glaucoma.},
}
@article {pmid37531030,
year = {2023},
author = {Inoda, S and Takahashi, H and Takahashi, R and Hashimoto, Y and Yoshida, H and Takahashi, H and Takayama, T and Kawashima, H and Yanagi, Y},
title = {Visual and Anatomical Outcomes After Initial Intravitreal Faricimab Injection for Neovascular Age-Related Macular Degeneration in Patients with Prior Treatment History.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2703-2712},
pmid = {37531030},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this study was to investigate the safety and efficacy of a single injection of intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) who had a prior treatment history.<br><br>METHODS: A retrospective analysis was conducted on a consecutive cohort of 80 eyes of 75 patients with nAMD who had a prior history of treatment with an injection of anti-vascular endothelial growth factor. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and central choroidal thickness (CCT) were compared before the initial IVF injection and after a treatment interval matching the previous duration.<br><br>RESULTS: Central choroidal thickness decreased significantly following the IVF injection, but there was no significant change in BCVA or CST. Mean (&#xb1; standard deviation) BCVA changed from 0.34&#x2009;&#xb1;&#x2009;0.37 to 0.36&#x2009;&#xb1;&#x2009;0.40 (P&#x2009;=&#x2009;0.29), CST changed from 242&#x2009;&#xb1;&#x2009;72 to 242&#x2009;&#xb1;&#x2009;82&#xa0;&#xb5;m (P&#x2009;=&#x2009;0.99), and CCT changed from 189&#x2009;&#xb1;&#x2009;98 to 179&#x2009;&#xb1;&#x2009;97&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.0001). When the changes were evaluated according to the previous anti-VEGF agent administered, CCT was found to be significantly decreased by 8.7&#x2009;&#xb1;&#x2009;2.5&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.0001) in eyes previously treated with brolucizumab and by 13.1&#x2009;&#xb1;&#x2009;3.6&#xa0;&#xb5;m (P&#x2009;<&#x2009;0.0001) in eyes previously treated with aflibercept. No adverse events were observed during the study period.<br><br>CONCLUSION: Intravitreal faricimab injection is a safe and effective treatment for nAMD in terms of short-term outcomes. Further long-term study is necessary.},
}
@article {pmid37531029,
year = {2023},
author = {Creuzot Garcher, CP and Srour, M and Baudin, F and Dot, C and Nghiem-Buffet, S and Girmens, JF and Collin, C and Ponthieux, A and Delcourt, C},
title = {Management of Neovascular Age-Related Macular Degeneration Treatment in France from 2008-2018: The Nationwide LANDSCAPE Study.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2687-2701},
pmid = {37531029},
issn = {2193-8245},
abstract = {INTRODUCTION: The aim of this study was to describe the management of neovascular age-related macular degeneration (nAMD) in French patients between 2008 and 2018.<br><br>METHODS: This was a retrospective longitudinal cohort study using exhaustive nationwide health records from the French National Health Information database. Enrollment criteria were adults aged &#x2265; 50 years, nAMD diagnosis, or reimbursement for nAMD treatments (anti-vascular epithelial growth factor [VEGF] injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and treatments for other macular diseases (dexamethasone implant, laser). Main outcome measures were consumption of medical care and nAMD treatments per calendar year and number of years of follow-up.<br><br>RESULTS: Between 2008 and 2018, we identified 342,961 patients who have been treated for nAMD. Median duration of ophthalmological follow-up exceeded 7&#xa0;years (90&#xa0;months). The median annual number of ophthalmology consultations decreased from nine visits in year 1 after treatment initiation to four visits from year 7 onwards. The median duration of nAMD treatment was 10.1&#xa0;months for all patients, with 48.5% of patients undergoing treatment for < 1&#xa0;year. Only 24.4% of patients had maintained treatment at year 11. Patients remaining under treatment had a median of four anti-VEGF treatments per year throughout the 10-year study period. Ranibizumab was the more common first-line treatment (67.5% of patients) compared to aflibercept (32.4%). About 20% of patients who initiated treatment switched treatment at least once.<br><br>CONCLUSIONS: LANDSCAPE provides exhaustive nationwide data on the real-world management of nAMD in France over a 10-year period. Further investigation into short treatment duration is required, especially in terms of understanding its relation to visual outcomes.},
}
@article {pmid37529808,
year = {2023},
author = {Oikonomidis, K and Almpanidou, S and Talimtzi, P and Kakavouti-Doudou, A and Metaxas, SM and Karampatakis, V},
title = {Compliance With the Use of Low-Vision Aids in a Greek Population: An Explorative Study.},
journal = {Cureus},
volume = {15},
number = {7},
pages = {e42730},
pmid = {37529808},
issn = {2168-8184},
abstract = {The aim of this study is to investigate the compliance with low-vision aids (LVAs) among patients with low vision (LV) in a Greek population. An explorative study was conducted in a sample of patients with LV attending our outpatient unit at the School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. Patients' demographics and daily visual demands were recorded, and they were administered with the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) at baseline. Participants were trained in the use of a wide range of LVAs before their prescription. Evaluation of the use of the LVAs was conducted at one year after the baseline using a structured phone survey. A total of 100 LV patients were included, with 68% of them being older than 65 years and 50 being males. The main cause of LV (57.0%) was age-related macular degeneration, and the mean VFQ-25 score at baseline was 49.2 (SD= 17.8). Overall, 75 patients had been prescribed LVAs, with 76.0% of these patients preferring an optical aid. The vast majority (98.7%) of these patients stated using the LVA one year after the baseline, and 62.1% of them reported using the aid often to very often. Significantly, 76% of these patients reported that their quality of life was positively affected by the use of the aid, and 97.3% would recommend the use of LVA to another individual with the same problem. Providing appropriate training before the prescription is of high significance to improve the rate of compliance with the use of LVAs. These results can be used to develop appropriate strategies in this field.},
}
@article {pmid37529008,
year = {2023},
author = {Chen, X and Tzekov, R and Su, M and Zhu, Y and Han, A and Li, W},
title = {Hydrogen peroxide-induced oxidative damage and protective role of peroxiredoxin 6 protein via EGFR/ERK signaling pathway in RPE cells.},
journal = {Frontiers in aging neuroscience},
volume = {15},
number = {},
pages = {1169211},
pmid = {37529008},
issn = {1663-4365},
abstract = {INTRODUCTION: Damage to retinal pigment epithelium (RPE) cells caused by oxidative stress is closely related to the pathogenesis of several blinding retinal diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, and other inherited retinal degenerative conditions. However, the mechanisms of this process are poorly understood. Hence, the goal of this study was to investigate hydrogen peroxide (H2O2)-induced oxidative damage and protective role of peroxiredoxin 6 (PRDX6) protein via EGFR/ERK signaling pathway in RPE cells.<br><br>METHODS: Cells from a human RPE cell line (ARPE-19 cells) were treated with H2O2, and then cell viability was assessed using the methyl thiazolyl tetrazolium assay. Cell death and reactive oxygen species (ROS) were detected by flow cytometry. The levels of PRDX6, epidermal growth factor receptor (EGFR), P38 mitogen-activated protein kinase (P38MAPK), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) were detected by Western blot assay. PRDX6 and EGFR were also detected via immunofluorescence staining.<br><br>RESULTS: Our results show that H2O2 inhibited cell viability, induced cell death, and increased ROS levels in ARPE-19 cells. It was also found that H2O2 decreased the levels of PRDX6, EGFR, and phosphorylated ERK but increased the levels of phosphorylated P38MAPK and JNK. PRDX6 overexpression was found to attenuate H2O2-induced inhibition of cell viability and increased cell death and ROS production in ARPE-19 cells. PRDX6 overexpression also increased the expression of EGFR and alleviated the H2O2-induced decrease in EGFR and phosphorylated ERK. Moreover, inhibition of epidermal growth factor-induced EGFR and ERK signaling in oxidative stress was partially blocked by PRDX6 overexpression.<br><br>DISCUSSION: Our findings indicate that PRDX6 overexpression protects RPE cells from oxidative stress damage caused by decreasing ROS production and partially blocking the inhibition of the EGFR/ERK signaling pathway induced by oxidative stress. Therefore, PRDX6 shows promise as a therapeutic target for the prevention of RPE cell damage caused by oxidative stress associated with retinal diseases.},
}
@article {pmid37527793,
year = {2023},
author = {Feng, J and Huang, C and Liang, L and Li, C and Wang, X and Ma, J and Guan, X and Jiang, B and Huang, S and Qin, P},
title = {The Association Between Eye Disease and Incidence of Dementia: Systematic Review and Meta-Analysis.},
journal = {Journal of the American Medical Directors Association},
volume = {24},
number = {9},
pages = {1363-1373.e6},
doi = {10.1016/j.jamda.2023.06.025},
pmid = {37527793},
issn = {1538-9375},
mesh = {Humans ; *Eye Diseases/epidemiology ; Incidence ; *Dementia, Vascular/epidemiology ; *Alzheimer Disease/epidemiology ; },
abstract = {OBJECTIVES: To better demonstrate the relationship between common eye diseases and the risk of dementia, we conducted a systematic review and meta-analysis of cohort studies to investigate the relationship between common eye diseases and dementia.<br><br>DESIGN: Systematic review and meta-analysis.<br><br>SETTING AND PARTICIPANTS: Patients with common eye diseases.<br><br>METHODS: We conducted a systematic search of articles published up to August 25, 2022, of online databases including PubMed, EMBASE, and Web of Science. We included cohort studies that evaluated the association of glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and cataracts with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Relative risks (RRs) and 95% CIs were pooled using random effects model, and heterogeneity was assessed by the I[2] statistic. Subgroup analysis and sensitivity analysis were also performed.<br><br>RESULTS: In total, 25 studies were included in the meta-analysis, with a total of 11,410,709 participants. Pooled estimates suggested an increased risk of all-cause dementia associated with AMD (RR, 1.29; 95% CI, 1.13-1.48), glaucoma (RR, 1.16; 95% CI, 1.03-1.32), DR (RR, 1.40; 95% CI, 1.21-1.63), and cataract (RR,1.23; 95% CI, 1.09-1.40); an increased risk of AD associated with AMD (RR, 1.27; 95% CI, 1.06-1.52), glaucoma (RR, 1.18; 95% CI, 1.02-1.38), DR (RR, 1.21; 95% CI, 1.04-1.41), and cataracts (RR,1.22; 95% CI, 1.07-1.38). No association was observed between incident VaD and any eye diseases. The results of subgroup analyses were consistent with those in meta-analysis of DR and risk of all-cause dementia. Meta-regressions suggested geographic regions as potential sources of heterogeneity for the association between AMD and all-cause dementia, AMD and AD, glaucoma and dementia, glaucoma, and AD, respectively.<br><br>CONCLUSIONS AND IMPLICATIONS: AMD, glaucoma, DR, and cataract may be associated with an increased risk of all-cause dementia and AD, but not VaD. However, the results should be interpreted cautiously because of the high heterogeneity and unstable findings in some subgroup analyses.},
}
@article {pmid37527760,
year = {2023},
author = {Arrigo, A and Aragona, E and Bianco, L and Antropoli, A and Berni, A and Saladino, A and Cosi, V and Bandello, F and Battaglia Parodi, M},
title = {The Localization of Intraretinal Cysts Has a Clinical Role on the 2-Year Outcome of Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {12},
pages = {1069-1079},
doi = {10.1016/j.oret.2023.07.025},
pmid = {37527760},
issn = {2468-6530},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Visual Acuity ; *Wet Macular Degeneration/diagnosis ; Retina ; *Cysts/diagnosis ; Atrophy ; },
abstract = {OBJECTIVE: To assess the relationship between ≥ 1 localizations of intraretinal fluid (IRF) within retinal layers and the 2-year outcome in a cohort of neovascular age-related macular degeneration (AMD) eyes.<br><br>DESIGN: Retrospective case series.<br><br>PARTICIPANTS: Two hundred forty-three eyes of 243 AMD patients affected by type 1 and type 2 macular neovascularization (MNV).<br><br>METHODS: We analyzed data considering MNV onset, 1-year, and 2-year timepoints. Optical coherence tomography images were used to classify MNV types, distinguish different types of fluids and assess IRF localization within retinal layers. A subcohort of eyes were also analyzed by OCT angiography.<br><br>MAIN OUTCOME MEASURES: The association between IRF cyst localization and both visual outcome and onset of outer retinal atrophy at 2-year follow-up.<br><br>RESULTS: Macular neovascularizations were distributed as type 1 (69%) and type 2 (31%). The mean number of intravitreal injections was 7 &#xb1; 2 at 1-year follow-up and 5 &#xb1; 2 at 2-year follow-up. Baseline best-corrected visual acuity was 0.4 &#xb1; 0.3 logarithm of the minimum angle of resolution, improving to 0.3 &#xb1; 0.4 at 2-year follow-up (P < 0.01). Outer retinal atrophy occurred in 24% of cases at 1 year and 39% of cases at 2-year follow-up. Intraretinal fluid localizations at the level of IPL-INL and OPL-ONL at baseline were associated with the worst functional and anatomical outcome. Moreover, the presence of IRF at baseline was associated with greater impairment of the intraretinal vascular network.<br><br>CONCLUSIONS: The localization of IRF at the level of IPL-INL and OPL-ONL retinal layers represents a negative prognostic biomarker for the morphologic and functional outcomes of neovascular AMD.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37527696,
year = {2023},
author = {Degirmenci, C and Afrashi, F and Yarimada, S and Ceper, SB and Nalcaci, S and Akkin, C and Mentes, J},
title = {Investigation of the choroidal structure in non-neovascular age-related macular degeneration patients with reticular pseudodrusen.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {43},
number = {},
pages = {103726},
doi = {10.1016/j.pdpdt.2023.103726},
pmid = {37527696},
issn = {1873-1597},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; Tomography, Optical Coherence/methods ; *Photochemotherapy/methods ; Photosensitizing Agents ; *Retinal Drusen/diagnosis ; Choroid/diagnostic imaging/blood supply ; *Macular Degeneration ; Retrospective Studies ; Fluorescein Angiography/methods ; },
abstract = {BACKGROUND: This study aimed to compare choroidal thickness, total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI) in patients with reticular pseudodrusen (RPD) and drusen.<br><br>METHODS: A total of 100 eyes of 100 patients with non-neovascular age related macular degeneration (AMD) with five or more medium drusen (63-125&#xa0;&#xb5;m) and RPD in two or more quadrants were recruited to the study. 48 eyes of 48 patients with RPD were assigned as Group 1 and 52 eyes of 52 patients with drusen were assigned as Group 2. 40 right eyes of 40 healthy subjects were included as controls. Patients with neovascular AMD or advanced non-neovascular AMD were excluded from the study. After a detailed ophthalmic examination, infrared reflectance images and OCT with enhanced depth imaging mode was obtained from all patients. TCA, SA, LA and CVI were calculated using the Image J program. The data were analyzed for statistics using SPSS software.<br><br>RESULTS: The female/male ratio was 56/44 in the patient groups and 20/20 in the control group. The mean age was 73.63&#xb1;6.14 (61-91) years for Group 1 and 69.43&#xb1; 6.97 (59-87) years for Group 2 (p=0.005). The mean age of Group 3 patients was 71.14&#xb1;8.17 (60-79) years and was statistically similar to Groups 1 and 2 (p=0.09 and p=0.12, respectively). Choroidal thickness, TCA, SA and LA were significantly lower in Group 1 (p<0.001). CVI and foveal thicknesses were not significantly different between Group 1 and 2 (p=0.214 and p=0.384 respectively). CVI was significantly lower in Group 3 (p<0.01). RPD was most commonly seen in the superior quadrant followed by temporal, nasal, and inferior quadrants.<br><br>CONCLUSIONS: TCA, SA and LA, which reflect choroidal vasculature, were decreased in patients with RPD. These parameters can help evaluate the pathophysiology of the disease.},
}
@article {pmid37527207,
year = {2023},
author = {Keenan, TDL and Loewenstein, A},
title = {Artificial intelligence for home monitoring devices.},
journal = {Current opinion in ophthalmology},
volume = {34},
number = {5},
pages = {441-448},
doi = {10.1097/ICU.0000000000000981},
pmid = {37527207},
issn = {1531-7021},
abstract = {PURPOSE OF REVIEW: Home monitoring in ophthalmology is appropriate for disease stages requiring frequent monitoring or rapid intervention, for example, neovascular age-related macular degeneration (AMD) and glaucoma, where the balance between frequent hospital attendance versus risk of late detection is a constant challenge. Artificial intelligence approaches are well suited to address some challenges of home monitoring.<br><br>RECENT FINDINGS: Ophthalmic data collected at home have included functional (e.g. perimetry), biometric (e.g. intraocular pressure), and imaging [e.g. optical coherence tomography (OCT)] data. Potential advantages include early detection/intervention, convenience, cost, and visual outcomes. Artificial intelligence can assist with home monitoring workflows by handling large data volumes from frequent testing, compensating for test quality, and extracting useful metrics from complex data. Important use cases include machine learning applied to hyperacuity self-testing for detecting neovascular AMD and deep learning applied to OCT data for quantifying retinal fluid.<br><br>SUMMARY: Home monitoring of health conditions is useful for chronic diseases requiring rapid intervention or frequent data sampling to decrease risk of irreversible vision loss. Artificial intelligence may facilitate accurate, frequent, large-scale home monitoring, if algorithms are integrated safely into workflows. Clinical trials and economic evaluations are important to demonstrate the value of artificial intelligence-based home monitoring, towards improved visual outcomes.},
}
@article {pmid37526620,
year = {2023},
author = {Rajeswaren, V and Wagner, BD and Patnaik, JL and Mandava, N and Mathias, MT and Manoharan, N and De Carlo Forest, TE and Gnanaraj, R and Lynch, AM and Palestine, AG and , },
title = {Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {8},
pages = {1},
pmid = {37526620},
issn = {2164-2591},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; *Geographic Atrophy ; Interleukin-4 ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis ; Biomarkers ; Inflammation ; },
abstract = {PURPOSE: Chronic local inflammation underlies the pathogenesis of age-related macular degeneration (AMD) causing damage to the neurosensory retina. However, there is minimal research on systemic cell-mediated inflammation in AMD. Interleukin-4 (IL-4) is an immunoregulatory cytokine with an important role in modulating inflammation in chronic immune mediated disease. The purpose of this study was to: (1) investigate the role of systemic IL-4 in patients with intermediate AMD (iAMD) and in geographic atrophy (GA), an advanced form of AMD, compared to controls without AMD, and (2) determine if IL-4 levels are moderated by sex.<br><br>METHODS: We examined plasma levels of IL-4 in patients with iAMD, GA, and controls without AMD included in the University of Colorado AMD registry (August 2014 to June 2021). Cases and controls were defined by multimodal imaging. IL-4 was measured by multiplex immunoassay. Data were analyzed using a nonparametric rank based linear regression model fit to IL-4.<br><br>RESULTS: There were 199 patients with iAMD, 97 patients with GA, and 139 controls, with a percentage of female patients 61%, 55%, and 66%, respectively. We demonstrated significantly higher median IL-4 levels in GA (35.3; interquartile range [IQR] = 22.8-50.5) compared to iAMD (6.1; IQR = 2.2-11.3, P < 0.01) and controls (10.7; IQR = 5.0-16.8, P < 0.01). There were no significant differences in levels of IL-4 for cases and controls when stratified by sex.<br><br>CONCLUSIONS: These findings demonstrate a systemic immunological difference between iAMD and GA, indicating IL-4 may be a systemic biomarker for GA development.<br><br>TRANSLATIONAL RELEVANCE: The plasma biomarker IL-4 is significantly elevated in patients with GA.},
}
@article {pmid37525815,
year = {2023},
author = {Seluarize, G and Khairudin, MN and Ismail, F},
title = {Early Detection and Prevention of Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {15},
number = {6},
pages = {e41169},
pmid = {37525815},
issn = {2168-8184},
abstract = {Age-related macular degeneration (ARMD) is a group of age-related changes in the macula that can be potentially vision-threatening. In the current era, there are options for treatment modalities that aim to preserve a patient's vision. Poor vision not only serves as a significant factor in halting the elderly population from their daily activities, but it may also result in frequent falls, depression, and impairment of the ability to carry out activities of daily living. We would like to highlight in this clinical presentation simple tools for assessing the severity of disease and the importance of early detection of these patients.},
}
@article {pmid37523440,
year = {2023},
author = {},
title = {Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration Erratum Major Studies and Real-World Data: Errata.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {4},
pages = {422},
doi = {10.1097/APO.0000000000000629},
pmid = {37523440},
issn = {2162-0989},
}
@article {pmid37522020,
year = {2023},
author = {Alacamli, G and Kaderli, ST and Edebali, S and Alacamli, OG and Sul, S and Canbek, TD and Karalezli, A},
title = {Microvascular changes in obese adults detected by Optical Coherence Tomography Angiography.},
journal = {Romanian journal of ophthalmology},
volume = {67},
number = {2},
pages = {140-145},
pmid = {37522020},
issn = {2501-2533},
mesh = {Humans ; Adult ; Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; *Retinal Vessels/diagnostic imaging ; Prospective Studies ; Overweight/complications ; Obesity/complications ; },
abstract = {Aim: The aim of this prospective, controlled, non-randomized study was the comparison of the retinal microvascular parameters of obese and nonobese adults. Methods: 184 eyes of 92 subjects were separated to 3 groups. 68 eyes were in the normal weight group, with a body mass index between 18.5 and 24.5 kg/ m2, 60 eyes were in the overweight group, with a body mass index between 25-29.9 kg/ m2, and 56 eyes were in the obese group, with a body mass index ≥ 30 kg/ m2. All the volunteers were applied visual acuity, ocular motility testing, and slit lamp and mydriatic fundus examination. Optical Coherence Tomography Angiography (OCT-A) scanning was practiced with Optovue (Optovue, Inc; Fremont, CA) on a 6.00 x 6.00 mm macular region, in the central fovea. Results: 184 eyes of ninety-two patients were involved in this prospective study. The vessels' density (VD) in the optic nerve head (ONH) were significantly lower in the overweight and obese adult volunteers compared to the normal weight control group. However, other OCTA parameters (including macular VDs, Foveal avascular zone (FAZ), choriocapillaris plexus (CCP) area) did not demonstrate any significant difference between groups. Subfoveal choroidal thickness (SCT) was higher in the overweight and obese patients when compared to the normal weight control group. Central macular thickness (CMT) did not reveal any significant difference between groups. Conclusion: Even though clinicians are limited in pointing out any differential findings in obese patients only by fundus examination, OCT-A provides a predictable view of the microvascular changes in the retina and choroid in obese patients. Abbreviations: BMI = Body mass index, WHO = World Health Organization, AMD = Age-related macular degeneration, CT = Choroidal thickness, OCTA = Optical Coherence Tomography Angiography, (W/H) ratio = Waist-hip ratio, ETDRS = Early Treatment Diabetic Retinopathy Study, VD = Vessel density, SCP = Superficial capillary plexus, DCP = Deep capillary plexus, CCP = Flow area of the choriocapillaris, FAZ = Avascular zone, CMT = Central macular thickness, ONH = Optic nerve head.},
}
@article {pmid37522013,
year = {2023},
author = {Świerczyńska, M and Danikiewicz-Zagała, M and Sedlak, L and Nowak-Wąs, M and Wyględowska-Promieńska, D},
title = {Choroidal neovascularization associated with butterfly-shaped pattern dystrophy - a case report.},
journal = {Romanian journal of ophthalmology},
volume = {67},
number = {2},
pages = {185-190},
pmid = {37522013},
issn = {2501-2533},
mesh = {Mitochondrial Diseases ; Ranibizumab ; Tomography, Optical Coherence ; Diabetes Mellitus, Type 2 ; Fluorescein Angiography ; *Geographic Atrophy ; Aged ; Adult ; *Eye Abnormalities/complications ; Intravitreal Injections ; *Vitelliform Macular Dystrophy/complications/diagnosis/drug therapy ; Humans ; Intercellular Signaling Peptides and Proteins/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Deafness ; *Choroidal Neovascularization/diagnosis/drug therapy/etiology ; },
abstract = {The pattern dystrophies (PDs) are a group of primarily autosomal dominant inherited macular diseases that cause the deposition of lipofuscin in retinal pigment epithelium (RPE) and may lead to significant vision loss in later life. Patients can develop choroidal neovascularization (CNV) and/ or geographic atrophy (GA) and for this reason they are often misdiagnosed as age-related macular degeneration (AMD). We presented a case of a 66-year-old patient complaining of vision loss in the right eye (RE) for 8 months. At the initial examination, his best corrected visual acuity (BCVA) was 0.6 in the RE. Optical coherence tomography angiography (OCTA), fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA) allowed to diagnose butterfly-shaped PD in both eyes with choroidal neovascularization (CNV) in the RE. The patient was treated with three intravitreal anti-vascular epithelial growth factor (anti-VEGF, ranibizumab) injections during six weeks intervals, which improved and stabilized the BCVA of the RE to 0.7 during the over two-year observation period. Our report contributes to the still limited data regarding CNV associated with butterfly-shaped PDs and the results of treatment with ranibizumab. Abbreviations: AMD = age-related macular degeneration, anti-VEGF = anti-vascular epithelial growth factor, AOFVD = adult-onset foveomacular vitelliform dystrophy, BCVA = best corrected visual acuity, CNV = choroidal neovascularization, FAF = fundus autofluorescence, FFA = fundus fluorescein angiography, GA = geographic atrophy, LE = left eye, MIDD = maternally inherited diabetes and deafness, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, OU = oculus uterque, both eyes, PD = pattern dystrophy, PDSFF = pattern dystrophy simulating fundus flavimaculatus, PDT = photodynamic therapy, PRPH2 = peripherine-2, RE = right eye, RPE = retinal pigment epithelium, VA = visual acuity.},
}
@article {pmid37521880,
year = {2023},
author = {Kaldirim, HE and Ozkaya, A and Karabas, L and Alagoz, C and Alkin, Z and Altunay, O and Bayramoglu, SE and Bolukbasi, S and Demir, G and Demir, M and Demircan, A and Erden, B and Erdogan, G and Erdogan, M and Eris, E and Onur, IU and Osmanbasoglu, OA and Erkul, SO and Ozturk, M and Savur, F and Perente, I and Sarici, K and Sayin, N and Yasa, D and Yilmaz, I and Abdurrahmanoglu, ZY},
title = {Based on the Real-Life Data of Türkiye; Comparison of Anatomical and Functional Outcomes of Phakic and Pseudophakic Patients in Wet Type Age-Related Macular Degeneration.},
journal = {Beyoglu eye journal},
volume = {8},
number = {2},
pages = {73-80},
pmid = {37521880},
issn = {2587-0394},
abstract = {OBJECTIVES: The aim of the study was comparison of wet-type age-related macular degeneration in phakic and pseudophakic patients in terms of anatomical and functional success based on the real-life data of Türkiye.<br><br>METHODS: The multicenter retrospective real-life study data of the. retinal study group were used in this study. Among 867 eyes of 867 patients were included in the study. Patients were divided into two groups according to the status of the lens; phakic group and pseudophakic group. The follow-up period of the two groups, the number of injections at the 1[st], 2[nd], and 3[rd] years, and changes in the central macular thickness (CMT, &#x3bc;) and visual acuity (VA, logMAR) of the patients at the beginning, 6[th], 12[th], 24[th], and 36[th] months were examined.<br><br>RESULTS: In our study, the number of injections in the 1[st], 2[nd], and 3[rd] years, respectively, was 4.2&#xb1;2.0, 1.8&#xb1;1.9, and 1.0&#xb1;1.7 in the phakic group, and 3.9&#xb1;2.0, 1.7&#xb1;1.9, and 0.8&#xb1;1.4 in the pseudophakic group. When the two groups were compared in terms of the number of injections, there was a statistically significant difference in the 1st year, but there was no significant difference in the 2[nd] and 3[rd] years (p=0.001, p=0.350, and p=0.288, respectively). There was no statistically significant difference between the groups in terms of CMT in the baseline, 6[th], 12[th], 24[th], and 36[th] months (p=0.991, p=0.327, p=0.652, p=0.599, and p=0.873, respectively). Although there was no difference in VA between groups at the beginning (p=0.052), the phakic group showed statistically better VA in controls at 3[rd], 6[th], 12[th], 24[th], and 36[th] months (p=0.001, p=0.001, p=0.000, p=0.000, and p=0.003, respectively).<br><br>CONCLUSION: Differences in the number of injections and visual results between phakic and pseudophakic patients in wet type AMD may necessitate the creation of different treatment and follow-up protocols.},
}
@article {pmid37520467,
year = {2023},
author = {Messal, A and Abid, G and Abdi, M and Idder, A and Meroufel, N and Zemani-Fodil, F and Fodil, M},
title = {Association between CX3CR1 rs3732378 polymorphism and neovascular age-related macular degeneration in a sample of Algerian population.},
journal = {Molecular biology research communications},
volume = {12},
number = {2},
pages = {57-62},
pmid = {37520467},
issn = {2345-2005},
abstract = {Neovascular age-related macular degeneration (nAMD) is a progressive ocular disease, responsible for central visual loss and blindness in elderly population. Increase data demonstrate that genetic factors play an important role in pathogenesis process of this disease. The aim of this study is to investigate the association between rs3732378 polymorphism in CX3CR1 gene and nAMD in a sample of Algerian patients. This case-control study consisted of 72 patients with nAMD and 124 control subjects. DNA of participants was extracted using salting out method. Genotyping was carried out using the TaqMan real-time polymerase chain reaction method. Statistical analysis was performed by SPSS.21.0. The prevalence of the risk genotype AA was higher in the nAMD group than in control group (OR=5.02, 95% CI=1.44-17.4, P=0.011). In our sample of Algerian patients, the rs3732378 polymorphism is associated with nAMD. This result may support the role of CX3CR1 gene in the pathogenesis of nAMD.},
}
@article {pmid37517799,
year = {2023},
author = {Schmitz-Valckenberg, S and Saßmannshausen, M and Braun, M and Steffen, V and Gao, SS and Honigberg, L and Ferrara, D and Pfau, M and Holz, FG},
title = {Interreader Agreement and Longitudinal Progression of Incomplete/Complete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {12},
pages = {1059-1068},
doi = {10.1016/j.oret.2023.07.021},
pmid = {37517799},
issn = {2468-6530},
mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; Fluorescein Angiography ; *Macular Degeneration/pathology ; Retina/pathology ; Tomography, Optical Coherence/methods ; Atrophy ; },
abstract = {OBJECTIVE: To analyze the ability to evaluate changes over time of individual lesions of incomplete or complete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA and cRORA, respectively) in patients with intermediate age-related macular degeneration (iAMD).<br><br>DESIGN: OCT images from patients enrolled in Proxima B clinical trial (NCT02399072) were utilized.<br><br>PARTICIPANTS: Patients enrolled in the Proxima B clinical trial, from the cohort with geographic atrophy (GA) in 1 eye and iAMD in the other eye at baseline, were included.<br><br>METHODS: Junior and senior readers analyzed OCT images for the qualitative presence of 9 distinct early atrophic features (presence of zone of choroidal hypertransmission, attenuation and/or disruption of RPE, disruption of ellipsoid zone [EZ] and external limiting membrane [ELM], outer nuclear layer [ONL] thinning, outer plexiform layer [OPL]/inner nuclear layer [INL] subsidence, and hyporeflective wedge-shaped band). If deemed "present," 7 features were quantified with a predefined tolerance level of 50 &#x3bc;m (diameter for the zone of choroidal hypertransmission, zone of attenuation and/or disruption of the RPE, outer retinal thickness left/right vertical diameter, outer retinal thickness thinnest vertical diameter, annotation of EZ, and ELM disruption).<br><br>MAIN OUTCOME MEASURES: Interreader agreements for qualitative assessments (&#x3ba;-type statistics) and quantitative measurements (Bland-Altman statistics) were assessed. Progression of the lesion features over time was described.<br><br>RESULTS: Moderate agreement was found for presence of choroidal hypertransmission (&#x3ba;&#xa0;= 0.54), followed by ELM disruption (&#x3ba;&#xa0;= 0.58), OPL/INL subsidence (&#x3ba;&#xa0;= 0.46), and a hyporeflective wedge-shaped band (&#x3ba;&#xa0;= 0.47). Quantification measurements showed that choroidal hypertransmission had the highest agreement, whereas RPE attenuation/disruption had the lowest agreement. Longitudinal adjudicated changes for quantitative measurements of lesion progression showed that choroidal hypertransmission and ELM disruption showed significant progression, whereas EZ disruption and RPE attenuation/disruption did not.<br><br>CONCLUSIONS: The ability to evaluate changes over time for specific features of iRORA and cRORA was explored. The most robust biomarker was found to be choroidal hypertransmission, followed by ELM disruption and the qualitative markers of OPL/INL subsidence, as well as a wedge-shaped band. Disease progression over time could be assessed by some, but not all, spectral-domain OCT features that were explored.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37517527,
year = {2023},
author = {Awh, KC and Mahmoudzadeh, R and Salabati, M and Mansour, HA and Bechay, J and Magagna, J and Regillo, CD and Ho, AC and Garg, SJ and Hsu, J},
title = {Outcomes of Intentionally Suspending Treatment in Eyes With Advanced Neovascular Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {256},
number = {},
pages = {20-26},
doi = {10.1016/j.ajo.2023.07.022},
pmid = {37517527},
issn = {1879-1891},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Treatment Outcome ; Tomography, Optical Coherence ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To determine the outcomes of intentionally suspending anti-vascular endothelial growth factor (anti-VEGF) injections in eyes with advanced neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective cohort study.<br><br>METHODS: The study sample comprised 93 patients with nAMD and best available Snellen visual acuity (VA) &#x2264;20/400 in which anti-VEGF treatment was suspended by the treating physician. VA and optical coherence tomography (OCT) characteristics were evaluated to determine visual and anatomical outcomes up to 24 months after treatment suspension.<br><br>RESULTS: A total of 93 eyes from 93 patients who had received a mean of 16 anti-VEGF injections over a mean of 962 (SD 562) days were included. Comparing the treatment suspension visit to 24 months later, no significant change in mean central foveal thickness (163 [SD 118, range 19-704] &#x3bc;m vs 164 [SD 217, range 19-1468], P&#xa0;=&#xa0;.97), greatest lesion diameter (2547 [SD 1294, range 134-5707] &#x3bc;m vs 2442 [SD 1158, range 421-5305] &#x3bc;m, P&#xa0;=&#xa0;.43), greatest lesion thickness (194 [SD 136, range 0-618] &#x3bc;m vs 205 [SD 131, range 0-573] &#x3bc;m, P&#xa0;=&#xa0;.40), or VA (1.87 [SD 0.37], 20/1482, vs 1.94 [SD 0.28], 20/1741, P&#xa0;=&#xa0;.16) was found. In total, 7 eyes (7.5%) restarted treatment following a mean of 977 (SD 450) days after treatment suspension.<br><br>CONCLUSIONS: Suspension of anti-VEGF injections in eyes with advanced nAMD and VA &#x2264;20/400 may be reasonable in cases where the treating physician deems additional treatment is unlikely to provide benefit. Although the visual and anatomical findings remained stable after treatment suspension in most, a small number restarted anti-VEGF therapy, suggesting that eyes should still be monitored for disease progression.},
}
@article {pmid37517088,
year = {2023},
author = {Zhang, J and Jiang, J and Zhou, H and Li, S and Bian, W and Hu, L and Zhang, D and Xu, C and Sun, Y},
title = {LncRNA NORAD defects deteriorate the formation of age-related macular degeneration.},
journal = {Aging},
volume = {15},
number = {15},
pages = {7513-7532},
pmid = {37517088},
issn = {1945-4589},
mesh = {Mice ; Animals ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; *RNA, Long Noncoding/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; Sirtuin 1/genetics/metabolism ; *Macular Degeneration/genetics/metabolism ; Retinal Pigments/metabolism/pharmacology ; Retinal Pigment Epithelium ; },
abstract = {Long noncoding RNAs (lncRNAs) play important roles in the development of age-related macular degeneration (AMD). However, the effect of long non-coding RNA activated by DNA damage (NORAD) on AMD remains unknown. This study aimed to investigate the effect of NORAD on RPE cell senescence and degeneration. Irradiated adult retinal pigment epithelial cell line-19 (ARPE-19) and sodium iodate-treated mice were used as in vitro and in vivo AMD models. Results showed that irradiation-induced AMD characteristics of ARPE-19 and NORAD-knockdown aggravated cell cycle arrest in the G2/M phase, cell apoptosis and cell senescence along with the increased expression of phosphorylated P53 (p-P53) and P21. AMD factors C3, ICAM-1, APP, APOE, and VEGF-A were also increased by NORAD-knockdown. Moreover, NORAD-knockdown increased irradiation-induced reduction of mitochondrial homeostasis factors, (i.e., TFAM and POLG) and mitochondrial respiratory chain complex genes (i.e., ND1 and ND5) along with mitochondrial reactive oxygen species (ROS). We also identified a strong interaction of NORAD and PGC-1α and sirtuin 1 (SIRT1) in ARPE-19; that is, NORAD knockdown increases the acetylation of PGC-1α. In NORAD knockout mice, NORAD-knockout accelerated the sodium iodate-reduced retinal thickness reduction, function impairment and loss of retinal pigment in the fundus. Therefore, NORAD-knockdown accelerates retinal cell senescence, apoptosis, and AMD markers via PGC-1α acetylation, mitochondrial ROS, and the p-P53-P21signaling pathway, in which NORAD-mediated effect on PGC-1α acetylation might occur through the direct interaction with PGC-1α and SIRT1.},
}
@article {pmid37514920,
year = {2023},
author = {Hegde, KR and Ray, K and Szmacinski, H and Sorto, S and Puche, AC and Lengyel, I and Thompson, RB},
title = {Two-Photon Excited Fluorescence Lifetime Imaging of Tetracycline-Labeled Retinal Calcification.},
journal = {Sensors (Basel, Switzerland)},
volume = {23},
number = {14},
pages = {},
pmid = {37514920},
issn = {1424-8220},
support = {P01 AG081167/AG/NIA NIH HHS/United States ; R01 EY 030443/EY/NEI NIH HHS/United States ; R01 EY030443/EY/NEI NIH HHS/United States ; R01 AI172487/AI/NIAID NIH HHS/United States ; NIA 030443-03S1/AG/NIA NIH HHS/United States ; },
mesh = {Male ; Humans ; Female ; Aged ; Aged, 80 and over ; *Tetracycline/metabolism ; Pilot Projects ; Retina ; *Macular Degeneration/diagnostic imaging/metabolism ; Anti-Bacterial Agents/metabolism ; },
abstract = {Deposition of calcium-containing minerals such as hydroxyapatite and whitlockite in the subretinal pigment epithelial (sub-RPE) space of the retina is linked to the development of and progression to the end-stage of age-related macular degeneration (AMD). AMD is the most common eye disease causing blindness amongst the elderly in developed countries; early diagnosis is desirable, particularly to begin treatment where available. Calcification in the sub-RPE space is also directly linked to other diseases such as Pseudoxanthoma elasticum (PXE). We found that these mineral deposits could be imaged by fluorescence using tetracycline antibiotics as specific stains. Binding of tetracyclines to the minerals was accompanied by increases in fluorescence intensity and fluorescence lifetime. The lifetimes for tetracyclines differed substantially from the known background lifetime of the existing natural retinal fluorophores, suggesting that calcification could be visualized by lifetime imaging. However, the excitation wavelengths used to excite these lifetime changes were generally shorter than those approved for retinal imaging. Here, we show that tetracycline-stained drusen in post mortem human retinas may be imaged by fluorescence lifetime contrast using multiphoton (infrared) excitation. For this pilot study, ten eyes from six anonymous deceased donors (3 female, 3 male, mean age 83.7 years, range 79-97 years) were obtained with informed consent from the Maryland State Anatomy Board with ethical oversight and approval by the Institutional Review Board.},
}
@article {pmid37514145,
year = {2023},
author = {Sapowadia, A and Ghanbariamin, D and Zhou, L and Zhou, Q and Schmidt, T and Tamayol, A and Chen, Y},
title = {Biomaterial Drug Delivery Systems for Prominent Ocular Diseases.},
journal = {Pharmaceutics},
volume = {15},
number = {7},
pages = {},
pmid = {37514145},
issn = {1999-4923},
abstract = {Ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, have had a profound impact on millions of patients. In the past couple of decades, these diseases have been treated using conventional techniques but have also presented certain challenges and limitations that affect patient experience and outcomes. To address this, biomaterials have been used for ocular drug delivery, and a wide range of systems have been developed. This review will discuss some of the major classes and examples of biomaterials used for the treatment of prominent ocular diseases, including ocular implants (biodegradable and non-biodegradable), nanocarriers (hydrogels, liposomes, nanomicelles, DNA-inspired nanoparticles, and dendrimers), microneedles, and drug-loaded contact lenses. We will also discuss the advantages of these biomaterials over conventional approaches with support from the results of clinical trials that demonstrate their efficacy.},
}
@article {pmid37513839,
year = {2023},
author = {Korva-Gurung, I and Kubin, AM and Ohtonen, P and Hautala, N},
title = {Visual Outcomes of Anti-VEGF Treatment on Neovascular Age-Related Macular Degeneration: A Real-World Population-Based Cohort Study.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {7},
pages = {},
pmid = {37513839},
issn = {1424-8247},
support = {K71769//Oulu University Hospital/ ; 20220008//Finnish Eye Foundation/ ; },
abstract = {Neovascular age-related macular degeneration (nAMD) leads to visual impairment if not treated promptly. Intravitreal anti-VEGF drugs have revolutionized nAMD treatment in the past two decades. We evaluated the visual outcomes of anti-VEGF treatment in nAMD. A real-life population-based cohort study. The data included parameters for age, sex, age at diagnosis, laterality, chronicity, symptoms, visual outcomes, lens status, and history of intravitreal injections. A total of 1088 eyes (827 patients) with nAMD were included. Visual acuity was stable or improved in 984 eyes (90%) after an average of 36 ± 25 months of follow-up. Bevacizumab was the first-line drug in 1083 (99.5%) eyes. Vision improved ≥15 ETDRS letters in 377 (35%), >5 ETDRS letters in 309 (28%), and was stable (±5 ETDRS letters) in 298 (27%) eyes after anti-VEGF treatment. The loss of 5 ≤ 15 ETDRS letters in 44 (4%) eyes and ≥15 ETDRS letters in 60 (6%) eyes was noted. At the diagnosis of nAMD, 110 out of 827 patients (13%) fulfilled the criteria for visual impairment, whereas 179 patients (22%) were visually impaired after the follow-up. Improvement or stabilization in vision was noted in 90% of the anti-VEGF-treated eyes with nAMD. In addition, anti-VEGF agents are crucial in diminishing nAMD-related visual impairment.},
}
@article {pmid37513655,
year = {2023},
author = {Lendzioszek, M and Mrugacz, M and Bryl, A and Poppe, E and Zorena, K},
title = {Prevention and Treatment of Retinal Vein Occlusion: The Role of Diet-A Review.},
journal = {Nutrients},
volume = {15},
number = {14},
pages = {},
pmid = {37513655},
issn = {2072-6643},
mesh = {Humans ; *Retinal Vein Occlusion/prevention &amp; control ; *Macular Edema/etiology ; *Retinal Diseases ; *Macular Degeneration ; Diet ; },
abstract = {Retinal vein occlusion (RVO) is the second most common retinal disorder. In comparison to diabetic retinopathy or age-related macular degeneration, RVO is usually an unexpected event that carries a greater psychological impact. There is strong evidence to suggest that cardiovascular diseases are the most common risk factors in this pathology and it has long been known that a higher consumption of fish, nuts, fruits, and vegetables has a protective effect against these types of conditions. In the last several years, interest in plant-based diets has grown in both the general population and in the scientific community, to the point to which it has become one of the main dietary patterns adopted in Western countries. The aim of this review is to investigate the potential impact of macro- and micronutrients on retinal vein occlusion.},
}
@article {pmid37513514,
year = {2023},
author = {Nwagbo, U and Bernstein, PS},
title = {Understanding the Roles of Very-Long-Chain Polyunsaturated Fatty Acids (VLC-PUFAs) in Eye Health.},
journal = {Nutrients},
volume = {15},
number = {14},
pages = {},
pmid = {37513514},
issn = {2072-6643},
support = {P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY034497/EY/NEI NIH HHS/United States ; EY14800 and EY34497/EY/NEI NIH HHS/United States ; TA-NMT-0618-0736-UUT/FFB/Foundation Fighting Blindness/United States ; },
mesh = {Animals ; Humans ; *Diabetic Retinopathy ; Fatty Acids, Unsaturated/analysis ; Retina ; *Macular Degeneration/genetics ; Fatty Acids/analysis ; Mammals ; },
abstract = {Lipids serve many roles in the neural system, from synaptic stabilization and signaling to DNA regulation and neuroprotection. They also regulate inflammatory responses, maintain cellular membrane structure, and regulate the homeostatic balance of ions and signaling molecules. An imbalance of lipid subgroups is implicated in the progression of many retinal diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, and diet can play a key role in influencing these diseases' onset, progression, and severity. A special class of lipids termed very-long-chain polyunsaturated fatty acids (VLC-PUFAs) is found exclusively in mammalian vertebrate retinas and a few other tissues. They comprise <2% of fatty acids in the retina and are depleted in the retinas of patients with diseases like diabetic retinopathy and AMD. However, the implications of the reduction in VLC-PUFA levels are poorly understood. Dietary supplementation studies and ELOVL4 transgene studies have had positive outcomes. However, much remains to be understood about their role in retinal health and the potential for targeted therapies against retinal disease.},
}
@article {pmid37513223,
year = {2023},
author = {Sudhakaran, G and Chandran, A and Sreekutty, AR and Madesh, S and Pachaiappan, R and Almutairi, BO and Arokiyaraj, S and Kari, ZA and Tellez-Isaias, G and Guru, A and Arockiaraj, J},
title = {Ophthalmic Intervention of Naringenin Decreases Vascular Endothelial Growth Factor by Counteracting Oxidative Stress and Cellular Damage in In Vivo Zebrafish.},
journal = {Molecules (Basel, Switzerland)},
volume = {28},
number = {14},
pages = {},
pmid = {37513223},
issn = {1420-3049},
support = {RSP2023R414//King Saud University/ ; 2019-69012-29905//USDA-NIFA Sustainable Agriculture Systems/ ; },
mesh = {Animals ; *Zebrafish/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factors/metabolism ; *Diabetic Retinopathy/metabolism ; Oxidative Stress ; Glucose/pharmacology ; },
abstract = {Diabetes Mellitus is a metabolic disease that leads to microvascular complications like Diabetic retinopathy (DR), a major cause of blindness worldwide. Current medications for DR are expensive and report multiple side effects; therefore, an alternative medication that alleviates the disease condition is required. An interventional approach targeting the vascular endothelial growth factor (VEGF) remains a treatment strategy for DR. Anti-VEGF medicines are being investigated as the main therapy for managing vision-threatening complications of DR, such as diabetic macular oedema. Therefore, this study investigated the effect of flavonoid naringenin (NG) from citrus fruits on inhibiting early DR in zebrafish. When exposed to 130 mM glucose, the zebrafish larvae developed a hyperglycaemic condition accompanied by oxidative stress, cellular damage, and lipid peroxidation. Similarly, when adult zebrafish were exposed to 4% Glucose, high glucose levels were observed in the ocular region and massive destruction in the retinal membrane. High glucose upregulated the expression of VEGF. In comparison, the co-exposure to NG inhibited oxidative stress and cellular damage and restored the glutathione levels in the ocular region of the zebrafish larvae. NG regressed the glucose levels and cellular damage along with an inhibition of macular degeneration in the retina of adult zebrafish and normalized the overexpression of VEGF as a promising strategy for treating DR. Therefore, intervention of NG could alleviate the domestication of alternative medicine in ophthalmic research.},
}
@article {pmid37511686,
year = {2023},
author = {Wąż, P and Zorena, K and Murawska, A and Bielińska-Wąż, D},
title = {Classification Maps: A New Mathematical Tool Supporting the Diagnosis of Age-Related Macular Degeneration.},
journal = {Journal of personalized medicine},
volume = {13},
number = {7},
pages = {},
pmid = {37511686},
issn = {2075-4426},
abstract = {OBJECTIVE: A new diagnostic graphical tool-classification maps-supporting the detection of Age-Related Macular Degeneration (AMD) has been constructed.<br><br>METHODS: The classification maps are constructed using the ordinal regression model. In the ordinal regression model, the ordinal variable (the dependent variable) is the degree of the advancement of AMD. The other variables, such as CRT (Central Retinal Thickness), GCC (Ganglion Cell Complex), MPOD (Macular Pigment Optical Density), ETDRS (Early Treatment Diabetic Retinopathy Study), Snellen and Age have also been used in the analysis and are represented on the axes of the maps.<br><br>RESULTS: Here, 132 eyes were examined and classified to the AMD advancement level according to the four-point Age-Related Eye Disease Scale (AREDS): AREDS 1, AREDS 2, AREDS 3 and AREDS 4. These data were used for the creation of two-dimensional classification maps for each of the four stages of AMD.<br><br>CONCLUSIONS: The maps allow us to perform the classification of the patient's eyes to particular stages of AMD. The pairs of the variables represented on the axes of the maps can be treated as diagnostic identifiers necessary for the classification to particular stages of AMD.},
}
@article {pmid37511345,
year = {2023},
author = {Muraleva, NA and Kolosova, NG},
title = {P38 MAPK Signaling in the Retina: Effects of Aging and Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {24},
number = {14},
pages = {},
pmid = {37511345},
issn = {1422-0067},
support = {22-25-00224//Russian Foundation for Basic Research/ ; },
mesh = {Rats ; Animals ; Rats, Wistar ; Retina/metabolism ; *Macular Degeneration/metabolism ; *Retinal Diseases/metabolism ; Aging/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. Age is the greatest risk factor for AMD but the underlying mechanism remains unascertained, resulting in a lack of effective therapies. Growing evidence shows that dysregulation of the p38 MAPK signaling pathway (SP) contributes to aging and neurodegenerative diseases; however, information about its alteration in the retina with age and during AMD development is limited. To assess the contribution of alterations in p38 MAPK signaling to AMD, we compared age-associated changes in p38 MAPK SP activity in the retina between Wistar rats (control) and OXYS rats, which develop AMD-like retinopathy spontaneously. We analyzed changes in the mRNA levels of genes of this SP in the retina (data of RNA-seq) and evaluated the phosphorylation/activation of key kinases using Western blotting at different stages of AMD-like pathology including the preclinical stage. p38 MAPK SP activity increased in the retinas of healthy Wistar rats with age. The manifestation and dramatic progression of AMD-like pathology in OXYS rats was accompanied by hyperphosphorylation of p38 MAPK and MK2 as key p38 MAPK SP kinases. Retinopathy progression co-occurred with the enhancement of p38 MAPK-dependent phosphorylation of CryaB at Ser59 in the retina.},
}
@article {pmid37511119,
year = {2023},
author = {Dmitrenko, OP and Abramova, OI and Karpova, NS and Nurbekov, MK and Arshinova, ES},
title = {Relative Telomere Length Is Associated with the Risk of Development and Severity of the Course of Age-Related Macular Degeneration in the Russian Population.},
journal = {International journal of molecular sciences},
volume = {24},
number = {14},
pages = {},
pmid = {37511119},
issn = {1422-0067},
support = {&#x2116; FGFU-2022-0011: &#xab;Identification of significant bioindicators of various disorders of body functions&#xbb;.//The work was carried out within the framework of the state task of the Federal State Budgetary Institution "Research Institute of Pathology and Pathophysiology" &#x2116; FGFU-2022-0011: &#xab;Identification of significant bioindicators of various disorders of body fu/ ; },
mesh = {Male ; Humans ; Female ; *Telomere/genetics ; Aging/pathology ; Risk Factors ; *Macular Degeneration/genetics ; Biomarkers ; Disease Progression ; },
abstract = {One of the most significant factors for age-related macular degeneration (AMD) development is considered to be aging, the processes of which are closely associated with telomere shortening. The different forms, indicators of aggressiveness, and intensities of AMD can be observed in the same age group, confirming the need to find a biomarker for early diagnosis and be capable of monitoring the progression of the pathological process. Therefore, we investigated whether the relative telomere length (RTL) has any connection with the risk of development of disease and its progression. RTL was measured using RT-PCR in 166 people, including 96 patients with AMD. RTL was significantly lower in patients with AMD. Women were more likely to develop AMD than men (odds ratio (OR) = 9.53 × 10[6] vs. OR = 1.04 × 10[8], respectively). The decrease in RTL in patients reliably correlated with the progression of AMD, and the smallest RTL was observed in late-stage patients. RTL < 0.8 is a significant risk factor for disease progression. The results of our research showed that RTL may be considered as a potential biomarker and a promising predictor of disease progression in patients with early AMD.},
}
@article {pmid37510977,
year = {2023},
author = {Abdin, AD and Devenijn, M and Fulga, R and Langenbucher, A and Seitz, B and Kaymak, H},
title = {Prevalence of Geographic Atrophy in Advanced Age-Related Macular Degeneration (AMD) in Daily Practice.},
journal = {Journal of clinical medicine},
volume = {12},
number = {14},
pages = {},
pmid = {37510977},
issn = {2077-0383},
abstract = {PURPOSE: To investigate the prevalence of geographic atrophy (GA) in advanced age-related macular degeneration (AMD) and the proportion of eyes that would meet the indication criteria for treatment with the first intravitreal anti-C3 agent (pegcetacoplan).<br><br>METHODS: This retrospective cross-sectional study included all AMD patients who visited the Macular-Retina-Centre Oberkassel in 2021. Eyes were classified according to AMD stages. Eyes with GA were divided into two groups regarding foveal involvement. Baseline factors were compared between eyes with foveal GA (FGA) and eyes with non-foveal GA (NFGA) to identify predictive factors for foveal involvement.<br><br>RESULTS: A total of 2033 eyes from 1027 patients were included. AMD stage was early in 296 (14.5%) cases, intermediate in 368 (18.1%) cases, and advanced in 1249 (61.4%) cases. A total of 1204 (60%) eyes had GA [932 (77%) FGA and 272 (23%) NFGA], while 125 eyes (27.4% from eyes with advanced dry AMD) met the indication criteria for treatment with intravitreal pegcetacoplan. The proportion of eyes with neovascular AMD was significantly higher in the FGA group compared to the NFGA group [598 (64.2%) vs. 152 (55.8%), p = 0.01].<br><br>CONCLUSIONS: At least a quarter of eyes with advanced AMD would be suitable for the upcoming intravitreal pegcetacoplan therapy. Foveal involvement of GA in advanced AMD seems to be more likely in neovascular AMD than in dry AMD.},
}
@article {pmid37510825,
year = {2023},
author = {Sakaeda, Y and Kato, A and Kuwayama, S and Hirahara, S and Suzuki, N and Ogura, Y and Nakazawa, Y and Yasukawa, T},
title = {Long-Term Prognosis of Patients with Polypoidal Choroidal Vasculopathy Treated with Photodynamic Therapy.},
journal = {Journal of clinical medicine},
volume = {12},
number = {14},
pages = {},
pmid = {37510825},
issn = {2077-0383},
abstract = {We evaluated the long-term prognosis of the eyes of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). In total, 60 eyes of 57 patients diagnosed with PCV and treated with PDT were reviewed retrospectively in real-world settings. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), anatomical findings (vision-threatening findings), and treatment history were assessed. In total, 38 eyes underwent PDT as the initial treatment (initial PDT group) and 22 eyes underwent PDT as a rescue treatment (rescue PDT group). In the initial PDT group, 11 eyes (29%) did not require additional therapy throughout the observation period and maintained good BCVA. A total of 27 eyes (71%) underwent additional treatments and the mean BCVA was only stabilized for 2 years; thereafter, decreased vision occurred even with additional treatments. In the rescue PDT group, 22 eyes (95%) required additional treatment. Hard exudate, serous pigment epithelial detachment, and the total vision-threatening score were related to worse BCVA. Initial PDT may be effective in about 30% of cases with preservation of good vision and no need for additional treatment. However, patients with received rescue PDT needed additional treatment in most cases and the vision decreased in many cases.},
}
@article {pmid37510788,
year = {2023},
author = {Garweg, JG and Keiper, J and Pfister, IB and Schild, C},
title = {Functional Outcomes of Brolucizumab-Induced Intraocular Inflammation Involving the Posterior Segment-A Meta-Analysis and Systematic Review.},
journal = {Journal of clinical medicine},
volume = {12},
number = {14},
pages = {},
pmid = {37510788},
issn = {2077-0383},
abstract = {Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms: <Brolucizumab> AND <AMD> AND <intraocular inflammation>. The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1-6) IVB injections. A mean change in visual acuity of -14.6 ± 21.0 (median -6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of -25.3 ± 27.1 and -2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; p = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI.},
}
@article {pmid37510668,
year = {2023},
author = {Ekemiri, KK and Botchway, EN and Ezinne, NE and Sirju, N and Persad, T and Masemola, HC and Chidarikire, S and Ekemiri, CC and Osuagwu, UL},
title = {Comparative Analysis of Health- and Vision-Related Quality of Life Measures among Trinidadians with Low Vision and Normal Vision-A Cross-Sectional Matched Sample Study.},
journal = {International journal of environmental research and public health},
volume = {20},
number = {14},
pages = {},
pmid = {37510668},
issn = {1660-4601},
mesh = {Adult ; Quality of Life ; *Vision, Low ; Cross-Sectional Studies ; Surveys and Questionnaires ; Caribbean People ; Humans ; Visual Acuity ; *Diabetic Retinopathy ; },
abstract = {This cross-sectional study investigated the health-related and vision-related quality of life measures of adults with low vision compared to healthy individuals in Trinidad and Tobago. The health-related quality of life (HRQOL-14) and the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) were administered to 20 participants with low vision caused by diabetic retinopathy, retinitis pigmentosa, glaucoma, and macular degeneration, as well as 20 participants with no visual problems (control). Participants were recruited from the University Eye Clinic in Trinidad and Tobago. Compared to the controls, more participants in the low-vision group had lower age-adjusted NEI-VFQ-25 scores (48.3% vs. 95.1%; p < 0.001), had poor general (47.5% vs. 10%, p = 0.004) and mental (100% vs. 10%, p < 0.042) health, experienced greater activity limitation due to impairment or health problems (85% vs. 20%, p < 0.001), needed help with personal care (27.5% vs. 0%, p < 0.009) and daily routine (67.5% vs. 0%, p < 0.001), and experienced sleep problems (97.5% vs. 65%, p < 0.001) and symptoms of anxiety (100% vs. 90%, p = 0.042). All the diabetic retinopathy participants (100%, p = 0.028) had two or more impairments or vision problems compared to none in the other low-vision participants. In summary, the HRQOL-14 and NEI-VFQ-25 scores were significantly reduced in low-vision participants, who also demonstrated a greater vulnerability to poor quality of life in the presence of diabetes retinopathy. These findings have important clinical implications regarding offering appropriate support and interventions to improve quality of life outcomes in individuals with low vision.},
}
@article {pmid37510207,
year = {2023},
author = {Muntean, GA and Marginean, A and Groza, A and Damian, I and Roman, SA and Hapca, MC and Muntean, MV and Nicoară, SD},
title = {The Predictive Capabilities of Artificial Intelligence-Based OCT Analysis for Age-Related Macular Degeneration Progression-A Systematic Review.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {14},
pages = {},
pmid = {37510207},
issn = {2075-4418},
support = {PN-III-P2-2.1-PED-2021-2709//Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii/ ; },
abstract = {The era of artificial intelligence (AI) has revolutionized our daily lives and AI has become a powerful force that is gradually transforming the field of medicine. Ophthalmology sits at the forefront of this transformation thanks to the effortless acquisition of an abundance of imaging modalities. There has been tremendous work in the field of AI for retinal diseases, with age-related macular degeneration being at the top of the most studied conditions. The purpose of the current systematic review was to identify and evaluate, in terms of strengths and limitations, the articles that apply AI to optical coherence tomography (OCT) images in order to predict the future evolution of age-related macular degeneration (AMD) during its natural history and after treatment in terms of OCT morphological structure and visual function. After a thorough search through seven databases up to 1 January 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 1800 records were identified. After screening, 48 articles were selected for full-text retrieval and 19 articles were finally included. From these 19 articles, 4 articles concentrated on predicting the anti-VEGF requirement in neovascular AMD (nAMD), 4 articles focused on predicting anti-VEGF efficacy in nAMD patients, 3 articles predicted the conversion from early or intermediate AMD (iAMD) to nAMD, 1 article predicted the conversion from iAMD to geographic atrophy (GA), 1 article predicted the conversion from iAMD to both nAMD and GA, 3 articles predicted the future growth of GA and 3 articles predicted the future outcome for visual acuity (VA) after anti-VEGF treatment in nAMD patients. Since using AI methods to predict future changes in AMD is only in its initial phase, a systematic review provides the opportunity of setting the context of previous work in this area and can present a starting point for future research.},
}
@article {pmid37510188,
year = {2023},
author = {Goździewska, E and Wichrowska, M and Kocięcki, J},
title = {Early Optical Coherence Tomography Biomarkers for Selected Retinal Diseases-A Review.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {14},
pages = {},
pmid = {37510188},
issn = {2075-4418},
abstract = {Optical coherence tomography (OCT) is a non-invasive, easily accessible imaging technique that enables diagnosing several retinal diseases at various stages of development. This review discusses early OCT findings as non-invasive imaging biomarkers for predicting the future development of selected retinal diseases, with emphasis on age-related macular degeneration, macular telangiectasia, and drug-induced maculopathies. Practitioners, by being able to predict the development of many conditions and start treatment at the earliest stage, may thus achieve better treatment outcomes.},
}
@article {pmid37510153,
year = {2023},
author = {Chou, HD and Hwang, YS and Chen, KJ and Wu, WC and Liu, L and Ou, ST and Liao, W and Wang, CC and Lin, T and Lai, CC},
title = {Analysis of Retinol Binding Protein 4 and ABCA4 Gene Variation in Non-Neovascular Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {14},
pages = {},
pmid = {37510153},
issn = {2075-4418},
support = {CMRPG3J1881//Chang Gung Memorial Hospital/ ; LBS-008-NC01//Lin BioScience, Inc./ ; },
abstract = {Age-related macular degeneration (AMD) may be associated with ABCA4 variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the ABCA4 variation, and AMD severity. Sixty-seven participants were grouped into healthy/mild AMD (n = 32) and severe AMD (n = 35) groups. The latter group was older than the former group and had higher levels of RBP4 (36.8 ± 8.3 vs. 30.4 ± 7.0 μg/mL, p = 0.0012). The ten participants with six ABCA4 linked-variants had higher RBP4 than those without (37.8 ± 7.7 vs. 32.4 ± 7.9 μg/mL; p = 0.026), and eight of them had severe AMD. Univariate analyses showed that severe AMD was related to older age (OR, 1.26; 95% CI, 1.13-1.40; p < 0.0001) and to higher RBP4 levels (OR, 1.12; 95% CI, 1.04-1.20; p = 0.003), whereas the linked ABCA4 variants had no associations. After adjustment, however, only age remained significantly associated with severe AMD. This pilot study shows a trend of higher plasma RBP4 levels in severe AMD or the ABCA4-linked variants, and further age-matched studies are warranted.},
}
@article {pmid37509549,
year = {2023},
author = {Huang, C and Ji, L and Kaur, A and Tian, H and Waduge, P and Webster, KA and Li, W},
title = {Anti-Scg3 Gene Therapy to Treat Choroidal Neovascularization in Mice.},
journal = {Biomedicines},
volume = {11},
number = {7},
pages = {},
pmid = {37509549},
issn = {2227-9059},
support = {R01 EY027749/EY/NEI NIH HHS/United States ; R43EY032827/EY/NEI NIH HHS/United States ; R43EY031238/EY/NEI NIH HHS/United States ; R43 EY031238/EY/NEI NIH HHS/United States ; R43 EY032827/EY/NEI NIH HHS/United States ; R24 EY028764/EY/NEI NIH HHS/United States ; R41EY027665/EY/NEI NIH HHS/United States ; R01EY027749/EY/NEI NIH HHS/United States ; R24EY028764/EY/NEI NIH HHS/United States ; P30 EY002520/EY/NEI NIH HHS/United States ; R41 EY027665/EY/NEI NIH HHS/United States ; },
abstract = {Neovascular age-related macular degeneration (nAMD) with choroidal neovascularization (CNV) is a leading cause of blindness in the elderly in developed countries. The disease is currently treated with anti-angiogenic biologics, including aflibercept, against vascular endothelial growth factor (VEGF) but with limited efficacy, treatment resistance and requirement for frequent intravitreal injections. Although anti-VEGF gene therapy may provide sustained therapy that obviates multiple injections, the efficacy and side effects related to VEGF pathway targeting remain, and alternative strategies to block angiogenesis independently of VEGF are needed. We recently reported that secretogranin III (Scg3) induces only pathological angiogenesis through VEGF-independent pathways, and Scg3-neutralizing antibodies selectively inhibit pathological but not physiological angiogenesis in mouse proliferative retinopathy models. Anti-Scg3 antibodies synergize dose-dependently with VEGF inhibitors in a CNV model. Here, we report that an adeno-associated virus-8 (AAV8) vector expressing anti-Scg3 Fab ameliorated CNV with an efficacy similar to that of AAV-aflibercept in a mouse model. This study is the first to test an anti-angiogenic gene therapy protocol that selectively targets pathological angiogenesis via a VEGF-independent mechanism. The findings support further safety/efficacy studies of anti-Scg3 gene therapy as monotherapy or combined with anti-VEGF to treat nAMD.},
}
@article {pmid37509540,
year = {2023},
author = {Aceves-Franco, LA and Sanchez-Aguilar, OE and Barragan-Arias, AR and Ponce-Gallegos, MA and Navarro-Partida, J and Santos, A},
title = {The Evolution of Triamcinolone Acetonide Therapeutic Use in Retinal Diseases: From Off-Label Intravitreal Injection to Advanced Nano-Drug Delivery Systems.},
journal = {Biomedicines},
volume = {11},
number = {7},
pages = {},
pmid = {37509540},
issn = {2227-9059},
abstract = {Ophthalmic drug delivery to the posterior segment of the eye has been challenging due to the complex ocular anatomy. Intravitreal injection of drugs was introduced to deliver therapeutic doses in the posterior segment. Different posterior segment diseases including age-related macular degeneration, diabetic macular edema, retinal vein occlusions, uveitis, and cystoid macular edema, among others, have been historically treated with intravitreal corticosteroids injections, and more recently with intravitreal corticosteroids drug implants. Triamcinolone acetonide (TA) is the most frequently used intraocular synthetic corticosteroid. Using nanoparticle-based TA delivery systems has been proposed as an alternative to intravitreal injections in the treatment of posterior segment diseases. From these novel delivery systems, topical liposomes have been the most promising strategy. This review is oriented to exhibit triamcinolone acetonide drug evolution and its results in treating posterior segment diseases using diverse delivery platforms.},
}
@article {pmid37509157,
year = {2023},
author = {Bora, PS},
title = {New Discoveries in Retinal Cell Degeneration and Retinal Diseases.},
journal = {Biomolecules},
volume = {13},
number = {7},
pages = {},
pmid = {37509157},
issn = {2218-273X},
mesh = {Humans ; Retina ; *Wet Macular Degeneration ; *Geographic Atrophy ; },
abstract = {Age-related macular degeneration (AMD) has two phenotypes: dry AMD and wet AMD [...].},
}
@article {pmid37508850,
year = {2023},
author = {Akinniyi, O and Rahman, MM and Sandhu, HS and El-Baz, A and Khalifa, F},
title = {Multi-Stage Classification of Retinal OCT Using Multi-Scale Ensemble Deep Architecture.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {10},
number = {7},
pages = {},
pmid = {37508850},
issn = {2306-5354},
abstract = {Accurate noninvasive diagnosis of retinal disorders is required for appropriate treatment or precision medicine. This work proposes a multi-stage classification network built on a multi-scale (pyramidal) feature ensemble architecture for retinal image classification using optical coherence tomography (OCT) images. First, a scale-adaptive neural network is developed to produce multi-scale inputs for feature extraction and ensemble learning. The larger input sizes yield more global information, while the smaller input sizes focus on local details. Then, a feature-rich pyramidal architecture is designed to extract multi-scale features as inputs using DenseNet as the backbone. The advantage of the hierarchical structure is that it allows the system to extract multi-scale, information-rich features for the accurate classification of retinal disorders. Evaluation on two public OCT datasets containing normal and abnormal retinas (e.g., diabetic macular edema (DME), choroidal neovascularization (CNV), age-related macular degeneration (AMD), and Drusen) and comparison against recent networks demonstrates the advantages of the proposed architecture's ability to produce feature-rich classification with average accuracy of 97.78%, 96.83%, and 94.26% for the first (binary) stage, second (three-class) stage, and all-at-once (four-class) classification, respectively, using cross-validation experiments using the first dataset. In the second dataset, our system showed an overall accuracy, sensitivity, and specificity of 99.69%, 99.71%, and 99.87%, respectively. Overall, the tangible advantages of the proposed network for enhanced feature learning might be used in various medical image classification tasks where scale-invariant features are crucial for precise diagnosis.},
}
@article {pmid37508566,
year = {2023},
author = {Choi, SW and Hong, HK and Jeon, J and Choi, JY and Kim, M and Kim, P and Lee, BC and Woo, SJ},
title = {FITC-Labeled RGD Peptides as Novel Contrast Agents for Functional Fluorescent Angiographic Detection of Retinal and Choroidal Neovascularization.},
journal = {Cells},
volume = {12},
number = {14},
pages = {},
pmid = {37508566},
issn = {2073-4409},
mesh = {Humans ; *Contrast Media ; Fluorescein-5-isothiocyanate ; Fluorescein/therapeutic use ; Endothelial Cells ; *Choroidal Neovascularization/diagnostic imaging/drug therapy ; Oligopeptides ; Coloring Agents ; },
abstract = {The development of choroidal neovascularization (CNV) is a crucial factor in the pathophysiology and prognosis of exudative age-related macular degeneration (AMD). Therefore, the detection of CNV is essential for establishing an appropriate diagnosis and treatment plan. Current ophthalmic imaging techniques, such as fundus fluorescent angiography and optical coherence tomography, have limitations in accurately visualizing CNV lesions and expressing CNV activity, owing to issues such as excessive dye leakage with pooling and the inability to provide functional information. Here, using the arginine-glycine-aspartic acid (RGD) peptide's affinity for integrin αvβ3, which is expressed in the neovascular endothelial cells in ocular tissues, we propose the use of fluorescein isothiocyanate (FITC)-labeled RGD peptide as a novel dye for effective molecular imaging of CNV. FITC-labeled RGD peptides (FITC-RGD2), prepared by bioconjugation of one FITC molecule with two RGD peptides, demonstrated better visualization and precise localization of CNV lesions than conventional fluorescein dyes in laser-induced CNV rodent models, as assessed using various imaging techniques, including a commercially available clinical fundus camera (Optos). These results suggest that FITC-RGD2 can serve as an effective novel dye for the diagnosis of neovascular retinal diseases, including AMD, by enabling early detection and treatment of disease occurrence and recurrence after treatment.},
}
@article {pmid37507918,
year = {2023},
author = {Kushwah, N and Bora, K and Maurya, M and Pavlovich, MC and Chen, J},
title = {Oxidative Stress and Antioxidants in Age-Related Macular Degeneration.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {7},
pages = {},
pmid = {37507918},
issn = {2076-3921},
support = {R01 EY024963/EY/NEI NIH HHS/United States ; R01 EY028100/EY/NEI NIH HHS/United States ; R01 EY031765/EY/NEI NIH HHS/United States ; EY031765, EY028100, and EY024963/EY/NEI NIH HHS/United States ; },
abstract = {Oxidative stress plays a crucial role in aging-related eye diseases, including age-related macular degeneration (AMD), cataracts, and glaucoma. With age, antioxidant reparative capacity decreases, and excess levels of reactive oxygen species produce oxidative damage in many ocular cell types underling age-related pathologies. In AMD, loss of central vision in the elderly is caused primarily by retinal pigment epithelium (RPE) dysfunction and degeneration and/or choroidal neovascularization that trigger malfunction and loss of photo-sensing photoreceptor cells. Along with various genetic and environmental factors that contribute to AMD, aging and age-related oxidative damage have critical involvement in AMD pathogenesis. To this end, dietary intake of antioxidants is a proven way to scavenge free radicals and to prevent or slow AMD progression. This review focuses on AMD and highlights the pathogenic role of oxidative stress in AMD from both clinical and experimental studies. The beneficial roles of antioxidants and dietary micronutrients in AMD are also summarized.},
}
@article {pmid37507908,
year = {2023},
author = {Nita, M and Grzybowski, A},
title = {Antioxidative Role of Heterophagy, Autophagy, and Mitophagy in the Retina and Their Association with the Age-Related Macular Degeneration (AMD) Etiopathogenesis.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {7},
pages = {},
pmid = {37507908},
issn = {2076-3921},
abstract = {Age-related macular degeneration (AMD), an oxidative stress-linked neurodegenerative disease, leads to irreversible damage of the central retina and severe visual impairment. Advanced age and the long-standing influence of oxidative stress and oxidative cellular damage play crucial roles in AMD etiopathogenesis. Many authors emphasize the role of heterophagy, autophagy, and mitophagy in maintaining homeostasis in the retina. Relevantly modifying the activity of both macroautophagy and mitophagy pathways represents one of the new therapeutic strategies in AMD. Our review provides an overview of the antioxidative roles of heterophagy, autophagy, and mitophagy and presents associations between dysregulations of these molecular mechanisms and AMD etiopathogenesis. The authors performed an extensive analysis of the literature, employing PubMed and Google Scholar, complying with the 2013-2023 period, and using the following keywords: age-related macular degeneration, RPE cells, reactive oxygen species, oxidative stress, heterophagy, autophagy, and mitophagy. Heterophagy, autophagy, and mitophagy play antioxidative roles in the retina; however, they become sluggish and dysregulated with age and contribute to AMD development and progression. In the retina, antioxidative roles also play in RPE cells, NFE2L2 and PGC-1α proteins, NFE2L2/PGC-1α/ARE signaling cascade, Nrf2 factor, p62/SQSTM1/Keap1-Nrf2/ARE pathway, circulating miRNAs, and Yttrium oxide nanoparticles performed experimentally in animal studies.},
}
@article {pmid37507866,
year = {2023},
author = {Salimiaghdam, N and Singh, L and Singh, MK and Chwa, M and Atilano, S and Mohtashami, Z and Nesburn, A and Kuppermann, BD and Kenney, MC},
title = {Potential Therapeutic Functions of PU-91 and Quercetin in Personalized Cybrids Derived from Patients with Age-Related Macular Degeneration, Keratoconus, and Glaucoma.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {7},
pages = {},
pmid = {37507866},
issn = {2076-3921},
support = {R01 EY027363/EY/NEI NIH HHS/United States ; R37 AG006168/AG/NIA NIH HHS/United States ; AG006168/AG/NIA NIH HHS/United States ; },
abstract = {The aim of this study is to investigate the therapeutic potential of higher doses of PU-91, quercetin, or in combination on transmitochondrial cybrid cell lines with various mtDNA haplogroups derived from patients with age-related macular degeneration (AMD), glaucoma (Glc), keratoconus (KC), and normal (NL) individuals. Cybrids were treated with PU-91 (P) (200 µM) alone, quercetin (Q) (20 µM) alone, or a combination of PU-91 and quercetin (P+Q) for 48 h. Cellular metabolism and the intracellular levels of reactive oxygen species (ROS) were measured by MTT and H2DCFDA assays, respectively. Quantitative real-time PCR was performed to measure the expression levels of genes associated with mitochondrial biogenesis, antioxidant enzymes, inflammation, apoptosis, and senescence pathways. PU-91(P) (i) improves cellular metabolism in AMD cybrids, (ii) decreases ROS production in AMD cybrids, and (iii) downregulates the expression of LMNB1 in AMD cybrids. Combination treatment of PU-91 plus quercetin (P+Q) (i) improves cellular metabolism in AMD, (ii) induces higher expression levels of TFAM, SOD2, IL6, and BAX in AMD cybrids, and (iii) upregulates CDKN1A genes expression in all disease cybrids. Our study demonstrated that the P+Q combination improves cellular metabolism and mitochondrial biogenesis in AMD cybrids, but senescence is greatly exacerbated in all cybrids regardless of disease type by the P+Q combined treatment.},
}
@article {pmid37507708,
year = {2023},
author = {Yang, JM and Kim, SJ and Park, S and Son, W and Kim, A and Lee, J},
title = {Exosomal miR-184 in the aqueous humor of patients with central serous chorioretinopathy: a potential diagnostic and prognostic biomarker.},
journal = {Journal of nanobiotechnology},
volume = {21},
number = {1},
pages = {242},
pmid = {37507708},
issn = {1477-3155},
support = {2018R1A5A1025511//National Research Foundation of Korea/ ; 2023IP0079-1//Asan Institute for Life Sciences, Asan Medical Center/ ; },
mesh = {Humans ; Aqueous Humor ; Biomarkers ; *Central Serous Chorioretinopathy/diagnosis/genetics/drug therapy ; Endothelial Cells ; Fluorescein Angiography/methods ; *MicroRNAs/genetics/therapeutic use ; Prognosis ; },
abstract = {BACKGROUND: Central serous chorioretinopathy (CSC) is the fourth most prevalent retinal disease leading to age-related macular degeneration (AMD) and retinal atrophy. However, CSC's pathogenesis and therapeutic target need to be better understood.<br><br>RESULTS: We investigated exosomal microRNA in the aqueous humor of CSC patients using next-generation sequencing (NGS) to identify potential biomarkers associated with CSC pathogenesis. Bioinformatic evaluations and NGS were performed on exosomal miRNAs obtained from AH samples of 62 eyes (42 CSC and 20 controls). For subgroup analysis, patients were divided into treatment responders (CSC-R, 17 eyes) and non-responders (CSC-NR, 25 eyes). To validate the functions of miRNA in CECs, primary cultured-human choroidal endothelial cells (hCEC) of the donor eyes were utilized for in vitro assays. NGS detected 376 miRNAs. Our results showed that patients with CSC had 12 significantly upregulated and 17 downregulated miRNAs compared to controls. miR-184 was significantly upregulated in CSC-R and CSC-NR patients compared to controls and higher in CSC-NR than CSC-R. In vitro assays using primary cultured-human choroidal endothelial cells (hCEC) demonstrated that miR-184 suppressed the proliferation and migration of hCECs. STC2 was identified as a strong candidate for the posttranscriptional down-regulated target gene of miR-184.<br><br>CONCLUSION: Our findings suggest that exosomal miR-184 may serve as a biomarker reflecting the angiostatic capacity of CEC in patients with CSC.},
}
@article {pmid37506496,
year = {2023},
author = {Verghese, P and Nyström, M and Foulsham, T and McGraw, PV},
title = {Eye movements in visual impairment.},
journal = {Vision research},
volume = {211},
number = {},
pages = {108296},
pmid = {37506496},
issn = {1878-5646},
support = {R01 EY027390/EY/NEI NIH HHS/United States ; R01 EY034370/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Eye Movements ; Saccades ; Vision, Ocular ; Pursuit, Smooth ; *Amblyopia ; *Vision, Low ; },
abstract = {This Special Issue describes the impact of visual impairment on visuomotor function. It includes contributions that examine gaze control in conditions associated with abnormal visual development such as amblyopia, dyslexia and neurofibromatosis as well as disorders associated with field loss later in life, such as macular degeneration and stroke. Specifically, the papers address both gaze holding (fixation), and gaze-following behavior (single saccades, sequences of saccades and smooth-pursuit) that characterize active vision in daily life and evaluate the influence of both pathological and simulated field loss. Several papers address the challenges to reading and visual search; describing how the patterns of eye movements in these real-world tasks adapt to visual impairment and highlighting how they could serve as diagnostic markers of visuomotor function.},
}
@article {pmid37504966,
year = {2023},
author = {Cho, HJ and Kang, KH and Yoon, W and Lee, J and Kim, CG and Kim, JW},
title = {Intravitreal Brolucizumab and Aflibercept for Polypoidal Choroidal Vasculopathy.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {39},
number = {9},
pages = {653-660},
doi = {10.1089/jop.2023.0030},
pmid = {37504966},
issn = {1557-7732},
mesh = {Humans ; *Angiogenesis Inhibitors/pharmacology/therapeutic use ; Polypoidal Choroidal Vasculopathy ; *Choroidal Neovascularization/diagnosis/drug therapy ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Tomography, Optical Coherence ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/pharmacology/therapeutic use ; Intravitreal Injections ; Treatment Outcome ; Fluorescein Angiography ; },
abstract = {Purpose: To compare the effectiveness of intravitreal injections of brolucizumab and aflibercept in patients with polypoidal choroidal vasculopathy (PCV). Methods: In total, 62 treatment-naive PCV eyes (62 patients) treated with intravitreal brolucizumab or aflibercept were analyzed retrospectively. All patients received a monthly loading injection of antivascular endothelial growth factor for 3 months, followed by further injections as required. Visual and anatomical outcomes were compared between drugs after 12 months of treatment. Results: The improvement in best-corrected visual acuity after 12 months of treatment was not significantly different between the brolucizumab-treated (22 eyes) and aflibercept-treated groups (40 eyes). However, in the brolucizumab-treated group, there was a significantly greater decrease in central retinal thickness (172 vs. 147 μm; P = 0.031) and subfoveal choroidal thickness after treatment (51 vs. 29 μm; P = 0.025). In addition, the regression rate of polypoidal lesions was significantly higher in the brolucizumab-treated group (77.3%, 17/22 eyes) than that in the aflibercept-treated group (45.0%, 18/40 eyes; P = 0.014). Sterile intraocular inflammation showing mild vitritis was observed in 1 of the 22 eyes (4.5%) of brolucizumab-treated patients. Conclusion: Intravitreal brolucizumab injections for PCV showed visual improvement comparable to that of aflibercept during the 12-month treatment period. However, brolucizumab was more effective than aflibercept for the regression of polypoidal lesions and caused a greater decrease in central retinal thickness and subfoveal choroidal thickness.},
}
@article {pmid37502831,
year = {2023},
author = {Yu, C and Lad, EM and Mathew, R and Littleton, S and Chen, Y and Schlepckow, K and Degan, S and Chew, L and Amason, J and Kalnitsky, J and Rickman, CB and Proia, AD and Colonna, M and Haass, C and Saban, DR},
title = {Microglia at Sites of Atrophy Restrict the Progression of Retinal Degeneration via Galectin-3 and Trem2 Interactions.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37502831},
issn = {2692-8205},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY021798/EY/NEI NIH HHS/United States ; R01 EY030906/EY/NEI NIH HHS/United States ; },
abstract = {Degenerative diseases of the outer retina, including age-related macular degeneration (AMD), are characterized by atrophy of photoreceptors and retinal pigment epithelium (RPE). In these blinding diseases, macrophages are known to accumulate ectopically at sites of atrophy, but their ontogeny and functional specialization within this atrophic niche remain poorly understood, especially in the human context. Here, we uncovered a transcriptionally unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and in human AMD. Using disease models, we found that conditional deletion of galectin-3 in microglia led to defects in phagocytosis and consequent augmented photoreceptor death, RPE damage and vision loss, suggestive of a protective role. Mechanistically, Trem2 signaling orchestrated the migration of microglial cells to sites of atrophy, and there, induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection, but only in a galectin-3-dependent manner, further signifying the functional interdependence of these two molecules. Likewise in elderly human subjects, we identified a highly conserved population of microglia at the transcriptomic, protein and spatial levels, and this population was enriched in the macular region of postmortem AMD subjects. Collectively, our findings reveal an atrophy-associated specialization of microglia that restricts the progression of retinal degeneration in mice and further suggest that these protective microglia are conserved in AMD.},
}
@article {pmid37499893,
year = {2023},
author = {Trivizki, O and Varcheie, M and Bello, S and Raden, I and Iyer, P and Marquez, M and Chaudhry, A and Al-Dabbagh, A and Gregori, G and Rosenfeld, PJ},
title = {Assessing Change in Exudative Age-Related Macular Degeneration With Macular Thickness Maps as a Surrogate Strategy for Remote Patient Monitoring.},
journal = {American journal of ophthalmology},
volume = {256},
number = {},
pages = {1-8},
pmid = {37499893},
issn = {1879-1891},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/diagnosis ; Retrospective Studies ; *Macula Lutea ; Tomography, Optical Coherence/methods ; Fovea Centralis ; },
abstract = {PURPOSE: To determine if macular thickness maps (MTMs) are sufficient to guide management of eyes with exudative age-related macular degeneration (eAMD), we compared the ability to detect change using MTMs with the ability to detect change using the entire optical coherence tomography (OCT) scan in patients undergoing therapy.<br><br>DESIGN: Retrospective, comparative diagnostic analysis.<br><br>METHODS: Patients with eAMD were imaged using macula-centered 6&#xa0;&#xd7;&#xa0;6-mm OCT scans (CIRRUS HD-OCT 5000; Zeiss). In each case, graders were asked to determine if there were changes that warranted a full clinical assessment after viewing 2 consecutive scans using one of 3 different imaging strategies: MTMs alone, individual foveal-centered B scans alone, or 5 macular B scans including the foveal-centered B scan. Graders were told the 2 scans were taken 2 weeks apart. The consensus ground truth was reached by the graders using a CIRRUS review station to evaluate all the information contained within the OCT scans.<br><br>RESULTS: A total of 53 eyes were included in this study with 1385 imaging sessions. The Fleiss kappa was highest when graders were given MTMs alone compared with the ground truth. When the averages of all 5 graders were compared with the ground truth, the MTMs alone showed the highest level of agreement (90.05%, SD 0.78%) followed by the central B scans (87.87%, SD 1.59%) and the 5-B scan method (86.512%, SD 0.64%).<br><br>CONCLUSION: MTMs alone provide sufficient information to easily identify recurrent exudation in patients with eAMD, and these maps may be all that is needed for remote monitoring.},
}
@article {pmid37498178,
year = {2023},
author = {Javed, A and Khanna, A and Palmer, E and Wilde, C and Zaman, A and Orr, G and Kumudhan, D and Lakshmanan, A and Panos, GD},
title = {Optical coherence tomography angiography: a review of the current literature.},
journal = {The Journal of international medical research},
volume = {51},
number = {7},
pages = {3000605231187933},
pmid = {37498178},
issn = {1473-2300},
mesh = {Humans ; Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; *Retina ; Retinal Vessels ; },
abstract = {This narrative review presents a comprehensive examination of optical coherence tomography angiography (OCTA), a non-invasive retinal vascular imaging technology, as reported in the existing literature. Building on the coherence tomography principles of standard OCT, OCTA further delineates the retinal vascular system, thus offering an advanced alternative to conventional dye-based imaging. OCTA provides high-resolution visualisation of both the superficial and deep capillary networks, an achievement previously unattainable. However, image quality may be compromised by factors such as motion artefacts or media opacities, potentially limiting the utility of OCTA in certain patient cohorts. Despite these limitations, OCTA has various potential clinical applications in managing retinal and choroidal vascular diseases. Still, given its considerable cost implications relative to current modalities, further research is warranted to justify its broader application in clinical practice.},
}
@article {pmid37497505,
year = {2023},
author = {Xie, H and Xu, W and Wang, YX and Wu, X},
title = {Deep learning network with differentiable dynamic programming for retina OCT surface segmentation.},
journal = {Biomedical optics express},
volume = {14},
number = {7},
pages = {3190-3202},
pmid = {37497505},
issn = {2156-7085},
abstract = {Multiple-surface segmentation in optical coherence tomography (OCT) images is a challenging problem, further complicated by the frequent presence of weak image boundaries. Recently, many deep learning-based methods have been developed for this task and yield remarkable performance. Unfortunately, due to the scarcity of training data in medical imaging, it is challenging for deep learning networks to learn the global structure of the target surfaces, including surface smoothness. To bridge this gap, this study proposes to seamlessly unify a U-Net for feature learning with a constrained differentiable dynamic programming module to achieve end-to-end learning for retina OCT surface segmentation to explicitly enforce surface smoothness. It effectively utilizes the feedback from the downstream model optimization module to guide feature learning, yielding better enforcement of global structures of the target surfaces. Experiments on Duke AMD (age-related macular degeneration) and JHU MS (multiple sclerosis) OCT data sets for retinal layer segmentation demonstrated that the proposed method was able to achieve subvoxel accuracy on both datasets, with the mean absolute surface distance (MASD) errors of 1.88 ± 1.96μm and 2.75 ± 0.94μm, respectively, over all the segmented surfaces.},
}
@article {pmid37496736,
year = {2023},
author = {Molcak, H and Jiang, K and Campbell, CJ and Matsubara, JA},
title = {Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration.},
journal = {Frontiers in neuroscience},
volume = {17},
number = {},
pages = {1216489},
pmid = {37496736},
issn = {1662-4548},
abstract = {Age-related macular degeneration (AMD) is a chronic and progressive inflammatory disease of the retina characterized by photoceptor loss and significant central visual impairment due to either choroidal neovascularization or geographic atrophy. The pathophysiology of AMD is complex and multifactorial, driven by a combination of modifiable and non-modifiable risk factors, molecular mechanisms, and cellular processes that contribute to overall disease onset, severity, and progression. Unfortunately, due to the structural, cellular, and pathophysiologic complexity, therapeutic discovery is challenging. While purinergic signaling has been investigated for its role in the development and treatment of ocular pathologies including AMD, the potential crosstalk between known contributors to AMD, such as the complement cascade and inflammasome activation, and other biological systems, such as purinergic signaling, have not been fully characterized. In this review, we explore the interactions between purinergic signaling, ATP release, and known contributors to AMD pathogenesis including complement dysregulation and inflammasome activation. We begin by identifying what is known about purinergic receptors in cell populations of the outer retina and potential sources of extracellular ATP required to trigger purinergic receptor activation. Next, we examine evidence in the literature that the purinergic system accelerates AMD pathogenesis leading to apoptotic and pyroptotic cell death in retinal cells. To fully understand the potential role that purinergic signaling plays in AMD, more research is needed surrounding the expression, distribution, functions, and interactions of purinergic receptors within cells of the outer retina as well as potential crosstalk with other systems. By determining how these processes are affected in the context of purinergic signaling, it will improve our understanding of the mechanisms that drive AMD pathogenesis which is critical in developing treatment strategies that prevent or slow progression of the disease.},
}
@article {pmid37495083,
year = {2023},
author = {Ehrlich, JR and Andes, LJ and Eisenberg, A and Saaddine, J and Lundeen, EA},
title = {Trends in the Diagnosed Prevalence and Incidence of Major Eye Diseases in Medicare Part B Fee-for-Service Beneficiaries 68 Years of Age or Older.},
journal = {Ophthalmology},
volume = {130},
number = {12},
pages = {1240-1247},
doi = {10.1016/j.ophtha.2023.07.020},
pmid = {37495083},
issn = {1549-4713},
mesh = {Humans ; Aged ; Female ; United States/epidemiology ; Male ; *Medicare Part B ; Incidence ; Cross-Sectional Studies ; Prevalence ; *Diabetic Retinopathy ; *Glaucoma/diagnosis/epidemiology ; *Macular Degeneration/diagnosis/epidemiology ; },
abstract = {PURPOSE: To study contemporary trends in the diagnosed prevalence and incidence of age-related eye diseases among Medicare Fee-for-Service (FFS) beneficiaries.<br><br>DESIGN: Analysis of Medicare administrative claims data.<br><br>PARTICIPANTS: Medicare FFS beneficiaries 68 years of age and older from 2005 through 2020 who were enrolled continuously in both Part A and Part B for 3 years, including the index year and a 2-year lookback period.<br><br>METHODS: Annual cross-sectional diagnosed prevalence and incidence rates were calculated. Age standardization was performed using the direct standardization method to account for changes in the age structure of the study population. Rates stratified by demographics (age, sex, race, and ethnicity) also were calculated.<br><br>MAIN OUTCOME MEASURES: Annual prevalence and incidence of diagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR) (among those with diabetes), and glaucoma.<br><br>RESULTS: At baseline, in 2005, 60% of included beneficiaries were female, 20% were 85 years of age or older, 86% were non-Hispanic White, and one-quarter had a diagnosis of diabetes. From 2005 through 2019, the&#xa0;prevalence of a diagnosis of any of the conditions studied increased from 16.4% (n = 3 628 996) to 17.9% (n&#xa0;= 3 731 281). Diagnosed incidence decreased over this period from 4.9% (n = 954 878) in 2005 to 4.2% in 2019 (n&#xa0;=&#xa0;757 696). The diagnosed prevalence of AMD increased from 6.8% (n&#xa0;= 1 504 770) to 9.4% (n&#xa0;= 1 965 176); the diagnosed prevalence of any DR among those with diabetes decreased from 9.3% (n&#xa0;= 504 135) to 9.0% (n&#xa0;=&#xa0;532 859), although the diagnosed prevalence of vision-threatening DR increased from 2.0% to 3.4%; and the diagnosed prevalence of any diagnosed glaucoma decreased from 8.8% (n&#xa0;= 1 951 141) to 8.1% (n&#xa0;= 1 692 837). In 2020, the diagnosed prevalence and incidence of all diagnoses decreased. During the study period, we detected demographic differences in the prevalence and incidence of diagnosis of each condition.<br><br>CONCLUSIONS: This study presents updated data on the prevalence and incidence of diagnosed major chronic, age-related eye diseases among Medicare FFS beneficiaries. Compared with older epidemiologic estimates, we found that the diagnosed prevalence of each condition studied was higher in more recent years. These findings may inform public health and policy planning and resource allocation to address the eye health of an increasingly older United States population.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid37494149,
year = {2023},
author = {Sayin, O and Altinkaynak, H},
title = {Macular Pigment Optical Density in First Degree Relatives of Age-Related Macular Degeneration Patients.},
journal = {Current eye research},
volume = {48},
number = {11},
pages = {1057-1062},
doi = {10.1080/02713683.2023.2242012},
pmid = {37494149},
issn = {1460-2202},
abstract = {PURPOSE: To measure the macular pigment optical density in first-degree relatives of patients with age-related macular degeneration and compare it with a healthy control group.<br><br>METHODS: One hundred and twenty-eight healthy subjects who were first-degree relatives of age-related macular degeneration patients were included in the study (Group 1). As the control group, 74 healthy subjects were included in the study (Group 2). The right eyes of all cases were included in the study. Macular pigment optical density was measured with a commercially available device (MPSII[&#xae;], Elektron Technology, Switzerland) using technology based on heterochromatic flicker photometry. Central foveal thickness and subfoveal choroidal thickness were measured with spectral-domain optical coherence tomography. Values were compared between the two groups.<br><br>RESULTS: There were 54 males and 74 females in Group 1 and 32 males and 42 females in Group 2. The mean&#x2009;&#xb1;&#x2009;SD ages of Group 1 and Group 2 were 49.0&#x2009;&#xb1;&#x2009;7.6 and 41.8&#x2009;&#xb1;&#x2009;8.6, respectively. Mean&#x2009;&#xb1;&#x2009;SD macular pigment optical density values of Group 1 and Group 2 were 0.43&#x2009;&#xb1;&#x2009;0.09 and 0.47&#x2009;&#xb1;&#x2009;0.12 (p&#x2009;=&#x2009;0.048), mean&#x2009;&#xb1;&#x2009;SD central foveal thickness were 208&#x2009;&#xb1;&#x2009;19 and 216&#x2009;&#xb1;&#x2009;8&#x2009;&#xb5;m (p&#x2009;=&#x2009;0.014), and mean&#x2009;&#xb1;&#x2009;SD subfoveal choroidal thickness were 232&#x2009;&#xb1;&#x2009;29 and 250&#x2009;&#xb1;&#x2009;21&#x2009;&#xb5;m (p&#x2009;=&#x2009;0.002), respectively.<br><br>CONCLUSION: The macular pigment optical density values were significantly lower in the first-degree relatives of patients with age-related macular degeneration than in the control group. Macular pigment optical density may be a marker for the development of age-related macular degeneration in the future in the first-degree relatives of age-related macular degeneration patients. Further prospective studies with a larger number of participants will be needed to confirm our results moreover, to clarify its benefit as an early diagnostic biomarker.},
}
@article {pmid37493854,
year = {2023},
author = {Koseoglu, ND and Grzybowski, A and Liu, TYA},
title = {Deep Learning Applications to Classification and Detection of Age-Related Macular Degeneration on Optical Coherence Tomography Imaging: A Review.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2347-2359},
pmid = {37493854},
issn = {2193-8245},
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly, more commonly in developed countries. Optical coherence tomography (OCT) is a non-invasive imaging device widely used for the diagnosis and management of AMD. Deep learning (DL) uses multilayered artificial neural networks (NN) for feature extraction, and is the cutting-edge technique for medical image analysis for diagnostic and prognostication purposes. Application of DL models to OCT image analysis has garnered significant interest in recent years. In this review, we aimed to summarize studies focusing on DL models used in classification and detection of AMD. Additionally, we provide a brief introduction to other DL applications in AMD, such as segmentation, prediction/prognostication, and models trained on multimodal imaging.},
}
@article {pmid37493655,
year = {2023},
author = {Hatamnejad, A and Dadak, R and Orr, S and Wykoff, C and Choudhry, N},
title = {Systematic review of efficacy and meta-analysis of safety of ranibizumab biosimilars relative to reference ranibizumab anti-VEGF therapy for nAMD treatment.},
journal = {BMJ open ophthalmology},
volume = {8},
number = {1},
pages = {},
pmid = {37493655},
issn = {2397-3269},
mesh = {Humans ; *Ranibizumab/adverse effects ; *Biosimilar Pharmaceuticals/adverse effects ; Angiogenesis Inhibitors/adverse effects ; Bevacizumab/adverse effects ; Vascular Endothelial Growth Factor A ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Vascular Endothelial Growth Factors ; Observational Studies as Topic ; },
abstract = {TOPIC: This systematic review and meta-analysis provides a summary of the efficacy and safety of ranibizumab biosimilars relative to reference ranibizumab anti-vascular endothelial growth factor (VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We conducted systematic searches from January 2003 to August 2022 on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials. We included studies reporting changes in early treatment diabetic retinopathy study-measured best-corrected visual acuity (BCVA), number of patients who lost or gained more than 15 letters in BCVA from baseline, changes in retinal thickness and adverse events between treatment arms. The following studies were excluded: studies that did not report visual outcomes following biosimilar and reference ranibizumab intravitreal injections, study arms combining anti-VEGF agents with laser or steroid injections, sham injections as a control comparator, studies without English full texts and non-comparative, observational study design.<br><br>RESULTS: Five studies reported on four randomised controlled trials (RCTs) and 1544 eyes at baseline were included in this systematic review and meta-analysis. The studies in our systematic review found no significant differences between reference ranibizumab and ranibizumab biosimilar medications (FYB201, SB11, RanizuRel and Lupin's ranibizumab) for visual and anatomical outcomes. No significant differences were detected between biosimilar and reference ranibizumab for treatment emergent adverse events (risk ratio, RR 1.06, 95% CI (0.91 to 1.23), p=0.45, I[2]=52%) or IOP-related adverse events with significant heterogeneity (RR 2.59, 95% CI (0.11 to 62.25), p=0.56, I[2]=76%).<br><br>CONCLUSION: This systematic review of four RCTs demonstrated no significant difference in visual outcomes, retinal thickness outcomes, as well as meta-analysis of adverse events between biosimilar and reference ranibizumab therapies for nAMD treatment.},
}
@article {pmid37492247,
year = {2023},
author = {Cho, SC and Park, KH and Park, SJ and Joo, K and Woo, SJ},
title = {Discontinuation of treatment and retreatment of neovascular age-related macular degeneration in the real-world: Bundang AMD cohort study report 5.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1204026},
pmid = {37492247},
issn = {2296-858X},
abstract = {INTRODUCTION: This single-center retrospective cohort study investigated the incidence rate and risk factors for the discontinuation of anti-vascular endothelial growth factor (VEGF) injections and retreatment in typical neovascular age-related macular degeneration (tnAMD) and polypoidal choroidal vasculopathy (PCV) in the real-world setting.<br><br>METHODS: A total of 488 eyes with either tnAMD (n = 334) or PCV (n = 154) followed up for &#x2265;3 years were analyzed. The discontinuation of treatment was defined as the cessation of anti-VEGF injections for 1 year or longer. Eyes with discontinuing treatment were subdivided into group A: eyes with stable responses (complete or incomplete resolution) and group B: those with no expectation of visual gain or poor response. The proportion and median time of discontinuation of treatment or retreatment were analyzed. The visual prognosis and the associated risk factors for the discontinuation of treatment or retreatment were also investigated.<br><br>RESULTS: The mean follow-up period was 8.1 &#xb1; 3.4 years. Of 488 eyes, discontinuation of the treatment occurred in 322 eyes (66.0%), and the median time to discontinuation was 1.5 years after the initial injection. Of 297 eyes with discontinuation of treatment excluding 25 eyes with vitrectomy or photodynamic therapy after the discontinuation of the injection, 277 eyes belonged to group A and the remaining 20 eyes belonged to group B. Of the 277 eyes discontinuing treatment with a stable response, 185 eyes (66.8%) were given retreatment. The median time to retreatment was 3.3 years after the discontinuation of the injections. PCV and the lower annual number of injections were the significant factors associated with discontinuation. Younger age, male gender, and PCV were the significant factors for the retreatment.<br><br>CONCLUSION: Our long-term real-world study showed that two-thirds of eyes with neovascular age-related macular degeneration (nAMD) had the discontinuation of the anti-VEGF injections and two-thirds of eyes discontinuing treatment with stable responses experienced retreatment. Long-term follow-up and regular monitoring are needed to detect the recurrence.},
}
@article {pmid37491579,
year = {2023},
author = {Pérez-Gutiérrez, L and Ferrara, N},
title = {Biology and therapeutic targeting of vascular endothelial growth factor A.},
journal = {Nature reviews. Molecular cell biology},
volume = {24},
number = {11},
pages = {816-834},
pmid = {37491579},
issn = {1471-0080},
mesh = {Female ; Humans ; *Vascular Endothelial Growth Factor A/genetics/metabolism ; Placenta Growth Factor ; Angiogenesis Inhibitors/therapeutic use ; *Neoplasms/drug therapy/genetics ; Biology ; },
abstract = {The formation of new blood vessels, called angiogenesis, is an essential pathophysiological process in which several families of regulators have been implicated. Among these, vascular endothelial growth factor A (VEGFA; also known as VEGF) and its two tyrosine kinase receptors, VEGFR1 and VEGFR2, represent a key signalling pathway mediating physiological angiogenesis and are also major therapeutic targets. VEGFA is a member of the gene family that includes VEGFB, VEGFC, VEGFD and placental growth factor (PLGF). Three decades after its initial isolation and cloning, VEGFA is arguably the most extensively investigated signalling system in angiogenesis. Although many mediators of angiogenesis have been identified, including members of the FGF family, angiopoietins, TGFβ and sphingosine 1-phosphate, all current FDA-approved anti-angiogenic drugs target the VEGF pathway. Anti-VEGF agents are widely used in oncology and, in combination with chemotherapy or immunotherapy, are now the standard of care in multiple malignancies. Anti-VEGF drugs have also revolutionized the treatment of neovascular eye disorders such as age-related macular degeneration and ischaemic retinal disorders. In this Review, we emphasize the molecular, structural and cellular basis of VEGFA action as well as recent findings illustrating unexpected interactions with other pathways and provocative reports on the role of VEGFA in regenerative medicine. We also discuss clinical and translational aspects of VEGFA. Given the crucial role that VEGFA plays in regulating angiogenesis in health and disease, this molecule is largely the focus of this Review.},
}
@article {pmid37491441,
year = {2024},
author = {Veeramani, P and Pilar Martin-Gutierrez, M and Agorogiannis, E and Hamilton, R and Griggs, T and Nicholson, L and Heng, LZ},
title = {Efficacy and Safety outcomes of a novel model to assess new medical retina referrals in a high-volume medical retina virtual clinic.},
journal = {Eye (London, England)},
volume = {38},
number = {1},
pages = {168-172},
pmid = {37491441},
issn = {1476-5454},
mesh = {Humans ; *Retina/diagnostic imaging ; Referral and Consultation ; *Diabetic Retinopathy/diagnosis ; Ambulatory Care Facilities ; Tomography, Optical Coherence/methods ; },
abstract = {BACKGROUND: Ophthalmology outpatient attendances have significantly increased recently with rising pressure from backlogs arising from the pandemic. Medical retina digital surveillance clinics for stable follow-up appointments are well established. We present a model for assessing new referrals and evaluating clinical outcomes and long-term sustainability in a complex high-volume medical retina service.<br><br>METHODS: Suitable routine new patient referrals were identified from electronic referrals and referred to this new pathway. Structured history, visual acuities, and intraocular pressures were recorded, and widefield colour fundus and optical coherence tomography imaging were performed at a imaging hub for asynchronous consultant-led review.<br><br>RESULTS: 1458 patients were invited to attend over four months, with a 13.2% did-not-attend (DNA) rate. Common diagnoses included stable diabetic retinopathy (19.9%), early age-related macular degeneration (6.7%), central serous retinopathy (8.8%), and retinal vein occlusion (6.3%). 7 patients (0.05%) required urgent same-day review. 61 (5.0%) required urgent face-to-face (F2F) assessment within two weeks. A total of 727 (59.0%) were either discharged or remained in the virtual pathway following their first visit.<br><br>CONCLUSION: This study encourages the use of a digital model that efficiently assesses suitable newly referred medical retina patients in both complex and local eye unit settings. This decreased the need for F2F clinics and resources. Further patient satisfaction surveys for digital services are currently being evaluated to guide long-term sustainability of this model.},
}
@article {pmid37491310,
year = {2023},
author = {Costa, RD and Thomaz Neto, FJ and Moustafa, MT and Atilano, SR and Chwa, M and Cáceres-Del-Carpi, J and Mohamed, MH and Kenney, MC and Kuppermann, BD},
title = {The role of mitochondrial genes on nuclear gene expression in neovascular age related macular degeneration: analysis of nuclear VEGF gene expression after ranibizumab treatment in cytoplasmic hybrid retinal pigment epithelial cell lines correlated with clinical evolution.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {44},
pmid = {37491310},
issn = {2056-9920},
support = {P30 EY034070/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: The present study tests the hypothesis that mitochondrial genes have retrograde signaling capacity that influences the expression of nuclear genes related to angiogenesis pathways. Cytoplasmic hybrid (cybrid) in vitro cell lines with patient specific mitochondria inserted into an immortalized retinal pigment epithelial cell line (ARPE-19) were used to test this hypothesis. This type of analysis can provide important information to identify the optimal regimen of anti-VEGF treatment, personalizing age-related macular degeneration (AMD) therapies.<br><br>METHODS: Mitochondria deficient ARPE-19 cells (Rho0) were fused with AMD donor's platelets to create individual cybrid cell lines containing mitochondria from patients with phenotypic AMD disease and nuclear DNA from the immortalized RPE cell line. The cybrids were treated with Ranibizumab (Lucentis, Genentech, San Francisco, CA), at 4 different concentrations for 24&#xa0;h, and subsequently the levels of reactive oxygen species (ROS), gene expression for VEGF-A, hypoxia-inducible factor 1-alpha (HIF1-a) and manganese superoxide dismutase (SOD2) were measured. The clinical evolution of the two AMD-donors were correlated with the molecular findings found in their 'personalized' cybrids.<br><br>RESULTS: Cybrids from Patient-01 showed down-regulation of gene expression of VEGF-A and HIF-1a at both 1X and 4X Ranibizumab concentrations. Patient-01 AMD cybrid cultures had an increase in the ROS levels at 1X (P&#x2009;=&#x2009;0.0317), no changes at 2X (P&#x2009;=&#x2009;0.8350) and a decrease at 4X (P&#x2009;=&#x2009;0.0015) and 10X (P&#x2009;=&#x2009;0.0011) of Ranibizumab. Clinically, Patient-01 responded to anti-VEGF therapy but eventually developed geographic atrophy. Patient-02 cybrids demonstrated up-regulation of gene expression of VEGF-A and HIF-1a at Ranibizumab 1X and 4X concentrations. There was decreased ROS levels with Ranibizumab 1X (P&#x2009;=&#x2009;0.1606), 2X (P&#x2009;=&#x2009;0.0388), 4X (P&#x2009;=&#x2009;0.0010) and 10X (P&#x2009;=&#x2009;&#x2009;<&#x2009;0.0001). Clinically, Patient-02 presented with a neovascular lesion associated with a prominent production of intraretinal fluid in clinical follow-up requiring regular and repeated intravitreal injections of Ranibizumab with recurrent subretinal fluid.<br><br>CONCLUSIONS: Our cybrid model has the potential to help personalize the treatment regimen with anti-VEGF drugs in patients with neovascular AMD. Further investigation is needed to better understand the role that the mitochondria play in the cellular response to anti-VEGF drugs. Future studies that focus on this model have the potential to help personalize anti-VEGF treatment.},
}
@article {pmid37490994,
year = {2023},
author = {Wang, H and Wang, C and Yao, Y and Duan, J and Liang, Y and Shang, Q},
title = {Analysis of long noncoding RNAs in the aqueous humor of wet age-related macular degeneration.},
journal = {Experimental eye research},
volume = {234},
number = {},
pages = {109576},
doi = {10.1016/j.exer.2023.109576},
pmid = {37490994},
issn = {1096-0007},
mesh = {Humans ; Aged ; Gene Expression Profiling ; *RNA, Long Noncoding/genetics ; Aqueous Humor/metabolism ; Signal Transduction ; RNA, Messenger/genetics/metabolism ; *Macular Degeneration ; Gene Regulatory Networks ; },
abstract = {Wet age-related macular degeneration (wAMD) is the main cause of irreversible blindness in the elderly, and its pathogenesis is still not fully understood. Long non-coding RNAs (lncRNAs) participated in the pathogenesis of a number of neovascular diseases, but their role in wAMD is less known. In order to reveal the potential role of lncRNAs in wAMD, we used high-throughput sequencing to assess lncRNAs and mRNAs expression profile in the aqueous humor of patients with wAMD and of patients with age-related cataract as control. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to identify the potential biological functions and signaling pathways of RNA. A coding-non-coding gene co-expression (CNC) network was constructed to identify the interaction of lncRNAs and mRNAs. Quantitative PCR was used to validate the expression of selected lncRNAs. We identified 1071 differentially expressed lncRNAs and 3658 differentially expressed mRNAs in patients with wAMD compared to controls. GO and KEGG analyses suggested that differentially expressed lncRNAs-coexpressed mRNAs were mainly enriched in Rab GTPase binding, GTPase activation, RAS signaling pathway and autophagy. The top 100 differentially expressed genes were selected to build the CNC network, which could be connected by 416 edges. LncRNAs are differentially expressed in the aqueous humor of patients with wAMD and they are involved in several pathogenetic pathways. These dysregulated lncRNAs and their target genes could represent promising therapeutic targets in wAMD.},
}
@article {pmid37490778,
year = {2023},
author = {Miki, M and Miyata, M and Ooto, S and Tamura, H and Ueda-Arakawa, N and Muraoka, Y and Miyake, M and Hata, M and Takahashi, A and Kido, A and Kogo, T and Uji, A and Tsujikawa, A},
title = {PREDICTORS OF 3-MONTH AND 1-YEAR VISUAL OUTCOMES AFTER VITRECTOMY WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR INJECTION FOR SUBMACULAR HEMORRHAGE.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {11},
pages = {1971-1979},
doi = {10.1097/IAE.0000000000003885},
pmid = {37490778},
issn = {1539-2864},
support = {21K09716//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Infant ; *Tissue Plasminogen Activator ; Fibrinolytic Agents/therapeutic use ; Vitrectomy/methods ; Prospective Studies ; Treatment Outcome ; Follow-Up Studies ; Retinal Hemorrhage/diagnosis/surgery/complications ; *Macular Degeneration/complications ; Retrospective Studies ; },
abstract = {PURPOSE: To investigate factors associated with 3-month or 1-year best-corrected visual acuity (BCVA) after vitrectomy with subretinal tissue plasminogen activator injection for submacular hemorrhage (SMH) and to identify the predictors of early displacement.<br><br>METHODS: This prospective cohort study included consecutive eyes with SMH complicating neovascular age-related macular degeneration or retinal macroaneurysm that underwent vitrectomy with subretinal tissue plasminogen activator injection and were followed up for at least 3 months. Parameters that correlated with 3-month BCVA, 1-year BCVA, and 2-week displacement grade (0-3) were identified.<br><br>RESULTS: Twenty-nine eyes of 29 patients (73.1 &#xb1; 8.4 years; neovascular age-related macular degeneration, 25 eyes) were included. Logarithm of the minimum angle of resolution BCVA improved 3 months after the surgery (baseline, 0.76 [20/115] &#xb1; 0.35; 3-month, 0.51 [20/65] &#xb1; 0.32; P = 0.006). In multivariable analyses, 1-year logarithm of the minimum angle of resolution BCVA correlated with age (P = 0.007, &#x3b2; = 0.39) and SMH recurrence within 1 year after surgery (P < 0.001, &#x3b2; = 0.65). Two-week displacement grade correlated with the contrast-to-noise ratio of SMH (P = 0.001, &#x3b2; = -0.54). Macular hole occurred in three eyes (10%) with small SMH size and was closed in all eyes via additional vitrectomy with an inverted internal limiting membrane flap technique.<br><br>CONCLUSION: The recurrence of SMH negatively affected the 1-year visual outcome after vitrectomy with subretinal tissue plasminogen activator injection for SMH. The contrast-to-noise ratio was a useful predictor of early SMH displacement, but not of 1-year BCVA. Further research is necessary to determine the optimal treatment to prevent SMH recurrence.},
}
@article {pmid37490756,
year = {2024},
author = {Alderman, DRB and Bracha, P},
title = {PNEUMATIC DISPLACEMENT OF HEMORRHAGIC BACILLARY LAYER DETACHMENT.},
journal = {Retinal cases &amp; brief reports},
volume = {18},
number = {5},
pages = {625-627},
doi = {10.1097/ICB.0000000000001463},
pmid = {37490756},
issn = {1937-1578},
mesh = {Humans ; Female ; Aged ; *Retinal Hemorrhage/diagnosis/etiology ; Retinal Detachment/diagnosis ; Receptors, Vascular Endothelial Growth Factor/antagonists &amp; inhibitors ; Wet Macular Degeneration/diagnosis/drug therapy ; Sulfur Hexafluoride/administration &amp; dosage ; Intravitreal Injections ; Endotamponade/adverse effects ; Recombinant Fusion Proteins/therapeutic use ; Visual Acuity ; Tomography, Optical Coherence ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {PURPOSE: The purpose of this study was to describe the management of a hemorrhagic bacillary layer detachment (BALAD) in a patient with neovascular age-related macular degeneration.<br><br>METHODS: The clinical records and imaging were reviewed.<br><br>RESULTS: A 74-year-old woman presented with acute-onset hemorrhagic neovascular age-related macular degeneration with a large hemorrhagic BALAD. The intra-BALAD hemorrhage was amenable to displacement with SF 6 pneumatic displacement with subsequent VA recovery.<br><br>CONCLUSION: Sulfur hexafluoride (SF 6) pneumatic displacement in combination with aflibercept injection is a viable means by which to manage a hemorrhagic BALAD in the context of neovascular age-related macular degeneration. Displacement of large intra-BALAD hemorrhages can result in good visual recovery.},
}
@article {pmid37490551,
year = {2023},
author = {Wei, P and He, M and Wang, Y and Han, G},
title = {High-Fat Diet Alters Acylcarnitine Metabolism of the Retina and Retinal Pigment Epithelium/Choroidal Tissues in Laser-Induced Choroidal Neovascularization Rat Models.},
journal = {Molecular nutrition &amp; food research},
volume = {67},
number = {19},
pages = {e2300080},
doi = {10.1002/mnfr.202300080},
pmid = {37490551},
issn = {1613-4133},
support = {21JCQNJC01800//Natural Science Foundation of Tianjin City/ ; 20JCQNJC01860//Natural Science Foundation of Tianjin City/ ; 22JCZDJC00280//Natural Science Foundation of Tianjin City/ ; TJWJ2022QN079//Tianjin Health Research Project/ ; TJWJ2022ZD009//Tianjin Health Research Project/ ; TJWJ2023MS0036//Tianjin Health Research Project/ ; YKQN2009//Science and Technology Foundation of Tianjin Eye Hospital/ ; TJYXZDXK-016A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; },
abstract = {SCOPE: Choroidal neovascularization (CNV) is age-related macular degeneration's (AMD) main pathological change. High-fat diet (HFD) is associated with a form of CNV; however, the specific mechanism is unclear. Mitochondrial dysfunction, characterized by abnormal acylcarnitine, occurs during metabolic screening of serum or other body tissues in AMD. This study investigates HFD's role in retinal and retinal pigment epithelium (RPE)/choroidal acylcarnitine metabolism in CNV formation.<br><br>METHODS AND RESULTS: Chow diet and HFD-BN rats are laser-treated to induce CNV. Acylcarnitine species are quantitatively characterized by ultrahigh-performance liquid chromatography-tandem mass spectrometry. Optical coherence tomography and fundus fluorescein angiography evaluate CNV severity. HFD promotes weight gain, dyslipidemia, and CNV formation. In CNV rats, few medium-chain fatty acids (MCFAs) acylcarnitine in the RPE/choroid are initially affected. When an HFD is administered to these, even MCFA acylcarnitine in the RPE/choroid is found to decline. However, in the retina, odd acylcarnitines are increased, revealing "an opposite" change within the RPE/choroid, accompanied by influencing glycolytic key enzymes. The HFD+CNV group incorporated fewer long-chain acylcarnitines, like C18:2, into the retina than controls.<br><br>CONCLUSIONS: HFD hastens choroidal neovascularization. The study comprehensively documented acylcarnitine profiles in a CNV rat model. Acylcarnitine's odd-even and carbon-chain length properties may guide&#xa0;future therapeutics.},
}
@article {pmid37490304,
year = {2023},
author = {Flores, R and Fradinho, AC and Pereira, RS and Mendes, JM and Seabra, MC and Tenreiro, S and Carneiro, &#xc2;},
title = {Identifying Imaging Predictors of Intermediate Age-Related Macular Degeneration Progression.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {7},
pages = {22},
pmid = {37490304},
issn = {2164-2591},
mesh = {Humans ; Prospective Studies ; *Macular Degeneration ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: Intermediate age-related macular degeneration (iAMD) is a risk factor for progression to advanced stages, but rates of progression vary between individuals. Predicting individual risk is advantageous for programing timely and effective treatment and for patient stratification into future clinical trials.<br><br>METHODS: We conducted a prospective and noninterventional study following patients with iAMD for 24 months. Optical coherence tomography parameters related with drusen, hyper-reflective foci (HRF), presence of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and ellipsoid zone (EZ) status were explored at the baseline. Patients were reclassified at the end of the follow-up period and divided according to their progression. A risk prediction model for progression to late AMD was developed.<br><br>RESULTS: A total of 135 patients were enrolled in the study and 30.4% developed late disease. A multivariate logistic regression model was created using those optical coherence tomography parameters, further optimized by backward feature elimination. Parameters offering the best fit in prediction progression were presence of iRORA, EZ status, drusen area and presence of HRF. iRORA is the feature that provides a higher probability of developing late AMD (odds ratio, 12.91; P = 0.000), followed by EZ disruption status (odds ratio, 3.54; P = 0.0018). The area under the receiver operating characteristic curve calculated for the testing set was 0.77 (95% confidence interval, 0.56-0.98).<br><br>CONCLUSIONS: The combination of iRORA and EZ disruption constitute a high risk of progression to complete RORA within 2 years.<br><br>TRANSLATIONAL RELEVANCE: We propose a practical and useful model to help clinicians in their daily practice in predicting individual progression to advanced AMD.},
}
@article {pmid37490230,
year = {2023},
author = {Rotake, DR and Ghosh, TN and Singh, SG},
title = {Electrochemical nano-biosensor based on electrospun indium zinc oxide nanofibers for the determination of complement component 3 protein.},
journal = {Mikrochimica acta},
volume = {190},
number = {8},
pages = {320},
pmid = {37490230},
issn = {1436-5073},
mesh = {Humans ; Aged ; *Zinc Oxide ; Zinc ; Complement C3 ; Indium ; *Nanofibers ; },
abstract = {Age-related macular degeneration (AMD) is a progressive chronic neurodegenerative retinal disease leading to vision loss, irreversible blindness, and visual impairment in older adults worldwide. Complement component 3 (C3) protein has been identified as the most predominant biomarker towards early diagnosis of AMD; therefore, there is an utmost requirement for non-invasive detection of C3 protein in the tear fluids of AMD patients. Considering this, we report an insightful electrochemical sensor capable of detecting clinically relevant concentrations ranging from 10 fg/mL to 1 μg/mL using electrospun indium-doped zinc oxide (InZnO) nanofibers as the transducing layer. The InZnO nanofibers have facilitated high anti-C3 antibody loading of 3.42 × 10[-9] mol/cm[2] and enhanced the overall charge transport mechanism at the sensor interface. The biofunctionalization process of the biosensor was investigated thoroughly using X-ray photoelectron spectroscopy (XPS) as well as different electrochemical techniques. The target C3 proteins were captured on the fabricated biosensor surface and determined through changes in charge transfer resistance (RCT) while executing electrochemical impedance spectroscopy (EIS) and peak current (Ip) in the case of cyclic voltammetry (CV) and differential pulse voltammetry (DPV), respectively. The InZnO nanofiber-based nano-biosensor demonstrated a very low limit of detections (LODs) of 5.214 fg/mL and 0.241 fg/mL with an excellent sensitivity of 4.6709 (ΔR/R) (g/mL)[-1] cm[-2] and 54.4939 (ΔIp/Ip)% (g/mL)[-1] cm[-2] for EIS and DPV techniques, respectively. By virtue of high antibody loading, ultrasensitive and ultra-selective capability, the indium-doped ZnO nanofibers show huge potential to be used as a high-performance diagnostic platform for AMD diagnosis.},
}
@article {pmid37489328,
year = {2023},
author = {Bouhout, S and Hébert, M and Jakubowska, W and Jaworski, L and Freeman, EE and Aubin, MJ},
title = {Impact of the COVID-19 Pandemic on Mental Health among Patients with Chronic Ocular Conditions.},
journal = {Vision (Basel, Switzerland)},
volume = {7},
number = {3},
pages = {},
pmid = {37489328},
issn = {2411-5150},
support = {0002//Philanthropic funds of the Vice-Dean of Research and Development of the Universit&#xe9; de Montr&#xe9;al./ ; 0001//National and International Networking Program of the Vision Health Research Network/ ; },
abstract = {The COVID-19 pandemic had significant impacts on the mental and visual health of patients. This cross-sectional, survey-based, multicentric study evaluates the state of mental and visual health among patients with chronic ocular diseases such as glaucoma, neovascular age-related macular degeneration, diabetic retinopathy, or chronic uveitis during the lockdown period of the COVID-19 pandemic. Mental health was assessed using three questionnaires: the Patient Health Questionnaire-9 (PHQ-9), the Impact of Event Scale-Revised (IES-R), and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25). A total of 145 patients completed the questionnaires. The PHQ-9 showed that most respondents (n = 89, 61%) had none or minimal depressive symptoms, while 31 (21%) had mild depressive symptoms, 19 (13%) had moderate depressive symptoms, 5 (3%) had moderately severe depressive symptoms, and 1 (1%) had severe depressive symptoms. Regarding stress surrounding the pandemic, the median IES-R showed mild distress in 16 (11%), moderate distress in 7 (5%), and severe distress in 4 (3%). The COVID-19 pandemic lockdowns had a negative impact on patients' mental health with close to 20% of the patients reporting at least moderately depressive symptoms and 19% reporting at least mildly distressful symptoms.},
}
@article {pmid37488646,
year = {2023},
author = {Xu, X and Zhou, R and Duan, Q and Miao, Y and Zhang, T and Wang, M and Jones, OD and Xu, M},
title = {Circulating macrophages as the mechanistic link between mosaic loss of Y-chromosome and cardiac disease.},
journal = {Cell &amp; bioscience},
volume = {13},
number = {1},
pages = {135},
pmid = {37488646},
issn = {2045-3701},
support = {#31771377/31571273/31371256//National Natural Science Foundation of China/ ; #MS2014SXSF038//Foreign Distinguished Scientist Program/ ; #GK201301001/201701005/GERP-17-45//National Department of Education Central Universities Research Fund/ ; 2009MSCRFE008300//US Maryland Stem Cell Research Fund/ ; 2019TS079/2019TS082//Outstanding Doctoral Thesis Fund/ ; },
abstract = {BACKGROUND: Genetics evidences have long linked mosaic loss of Y-chromosome (mLOY) in peripheral leukocytes with a wide range of male age-associated diseases. However, a lack of cellular and molecular mechanistic explanations for this link has limited further investigation into the relationship between mLOY and male age-related disease. Excitingly, Sano et al. have provided the first piece of evidence directly linking mLOY to cardiac fibrosis through mLOY enriched profibrotic transforming growth factor β1 (TGF-β1) regulons in hematopoietic macrophages along with suppressed interleukin-1β (IL-1β) proinflammatory regulons. The results of this novel finding can be extrapolated to other disease related to mLOY, such as cancer, cardiac disease, and age-related macular degeneration.<br><br>RESULTS: Sano et al. used a CRISPR-Cas9 gRNAs gene editing induced Y-chromosome ablation mouse model to assess results of a UK biobank prospective analysis implicating the Y-chromosome in male age-related disease. Using this in vivo model, Sano et al. showed that hematopoietic mLOY accelerated cardiac fibrosis and heart failure in male mice through profibrotic pathways. This process was linked to monocyte-macrophage differentiation during hematopoietic development. Mice confirmed to have mLOY in leukocytes, by loss of Y-chromosome genes Kdm5d, Uty, Eif2s3y, and Ddx3y, at similar percentages to the human population were shown to have accelerated rates of interstitial and perivascular fibrosis and abnormal echocardiograms. These mice also recovered poorly from the transverse aortic constriction (TAC) model of heart failure and developed left ventricular dysfunction at higher rates. This was attributed to aberrant proliferation of cardiac MEF-SK4&#x2009;+&#x2009;fibroblasts promoted by mLOY macrophages enriched in profibrotic regulons and lacking in proinflammatory regulons. These pro-fibrotic macrophages localized to heart and eventually resulted in cardiac fibrosis via enhanced TGF-&#x3b2;1 and suppressed IL-1&#x3b2; signaling. Furthermore, treatment of mLOY mice with TGF&#x3b2;1 neutralizing antibody was able to improve their cardiac function. This study by Sano et al. was able to provide a causative link between the known association between mLOY and male cardiac disease morbidity and mortality for the first time, and thereby provide a new target for improving human health.<br><br>CONCLUSIONS: Using a CRISPR-Cas9 induced Y-chromosome ablation mouse model, Sano et al. has proven mosaic loss of Y-chromosome in peripheral myeloid cells to have a causative effect on male mobility and mortality due to male age-related cardiac disease. They traced the mechanism of this effect to hyper-expression of the profibrotic TGF-&#x3b2;1 and reduced pro-inflammatory IL-1&#x3b2; signaling, attenuation of which could provide another potential strategy in improving outcomes against age-related diseases in men.},
}
@article {pmid37487362,
year = {2023},
author = {Nawaz, M and Uvaliyev, A and Bibi, K and Wei, H and Abaxi, SMD and Masood, A and Shi, P and Ho, HP and Yuan, W},
title = {Unraveling the complexity of Optical Coherence Tomography image segmentation using machine and deep learning techniques: A review.},
journal = {Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society},
volume = {108},
number = {},
pages = {102269},
doi = {10.1016/j.compmedimag.2023.102269},
pmid = {37487362},
issn = {1879-0771},
mesh = {Humans ; *Deep Learning ; Tomography, Optical Coherence/methods ; *Macular Degeneration ; Machine Learning ; *Glaucoma/diagnostic imaging ; },
abstract = {Optical Coherence Tomography (OCT) is an emerging technology that provides three-dimensional images of the microanatomy of biological tissue in-vivo and at micrometer-scale resolution. OCT imaging has been widely used to diagnose and manage various medical diseases, such as macular degeneration, glaucoma, and coronary artery disease. Despite its wide range of applications, the segmentation of OCT images remains difficult due to the complexity of tissue structures and the presence of artifacts. In recent years, different approaches have been used for OCT image segmentation, such as intensity-based, region-based, and deep learning-based methods. This paper reviews the major advances in state-of-the-art OCT image segmentation techniques. It provides an overview of the advantages and limitations of each method and presents the most relevant research works related to OCT image segmentation. It also provides an overview of existing datasets and discusses potential clinical applications. Additionally, this review gives an in-depth analysis of machine learning and deep learning approaches for OCT image segmentation. It outlines challenges and opportunities for further research in this field.},
}
@article {pmid37487237,
year = {2023},
author = {Maltsev, DS and Kulikov, AN and Perminova, SM and Burnasheva, MA and Vasiliev, AS},
title = {MULTIMODAL IMAGING IN NONEXUDATIVE CHOROIDAL NEOVASCULARIZATION: A Pilot Study of Status of Retinal Pigment Epithelium.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {11},
pages = {2019-2026},
doi = {10.1097/IAE.0000000000003896},
pmid = {37487237},
issn = {1539-2864},
mesh = {Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retinal Pigment Epithelium ; Pilot Projects ; Case-Control Studies ; Fluorescein Angiography ; *Choroidal Neovascularization/diagnosis ; Tomography, Optical Coherence ; *Macular Degeneration/diagnosis ; Multimodal Imaging ; },
abstract = {PURPOSE: To study the status of retinal pigment epithelium in nonexudative and active choroidal neovascularization (CNV) in neovascular age-related macular degeneration.<br><br>METHODS: Only treatment-na&#xef;ve neovascular age-related macular degeneration patients were enrolled in this prospective case-control study, including 17 eyes with nonexudative CNV (6 males and 11 females, 74.9 &#xb1; 10.0 years) and 28 eyes with active CNV (8 males and 20 females, 69.3 &#xb1; 6.8 years). All patients received a comprehensive ophthalmic examination, optical coherence tomography, dark-field scanning laser ophthalmoscopy, and fundus autofluorescence. The status of the retinal pigment epithelium was assessed with ImageJ software as the brightness of the CNV region on transillumination optical coherence tomography, dark-field scanning laser ophthalmoscopy, and fundus autofluorescence images. Choroidal neovascularization vessel density was measured based on optical coherence tomography angiography.<br><br>RESULTS: The brightness of CNV region in nonexudative CNV was statistically significantly lower than in active CNV with both optical coherence tomography transillumination (P = 0.004) and dark-field scanning laser ophthalmoscopy (P = 0.0015). No difference in brightness of the CNV region between nonexudative and active CNV was found based on fundus autofluorescence (P = 0.44). The vessel density of nonexudative CNV was statistically significantly higher than that of active CNV with a median value of 64.5% (95% confidential interval [CI] 53.4-79.0%) and 55.3% (95% CI 52.2-60.0%), respectively (P = 0.05).<br><br>CONCLUSION: Multimodal imaging revealed substantial alteration of the retinal pigment epithelium in active CNV but not in nonexudative CNV which correlates with the higher vessel density of nonexudative CNV.},
}
@article {pmid37484624,
year = {2023},
author = {Wu, CT and Lin, TY and Lin, CJ and Hwang, DK},
title = {The future application of artificial intelligence and telemedicine in the retina: A perspective.},
journal = {Taiwan journal of ophthalmology},
volume = {13},
number = {2},
pages = {133-141},
pmid = {37484624},
issn = {2211-5072},
abstract = {The development of artificial intelligence (AI) and deep learning provided precise image recognition and classification in the medical field. Ophthalmology is an exceptional department to translate AI applications since noninvasive imaging is routinely used for the diagnosis and monitoring. In recent years, AI-based image interpretation of optical coherence tomography and fundus photograph in retinal diseases has been extended to diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. The rapid development of portable ocular monitoring devices coupled with AI-informed interpretations allows possible home monitoring or remote monitoring of retinal diseases and patients to gain autonomy and responsibility for their conditions. This review discusses the current research and application of AI, telemedicine, and home monitoring devices on retinal disease. Furthermore, we propose a future model of how AI and digital technology could be implemented in retinal diseases.},
}
@article {pmid37484613,
year = {2023},
author = {Charles, J and Chau, TTH},
title = {Five-year outcome of aflibercept intravitreal injection in naïve patients with neovascular age-related macular degeneration using a modified treat-and-extend regimen: Results from a prospective observational study.},
journal = {Taiwan journal of ophthalmology},
volume = {13},
number = {2},
pages = {219-224},
pmid = {37484613},
issn = {2211-5072},
abstract = {PURPOSE: The purpose is to study the 5-year results of aflibercept monotherapy using an individualized regimen in naïve patients with neovascular AMD (nAMD).<br><br>MATERIALS AND METHODS: This is a prospective observational study including na&#xef;ve nAMD patients who underwent aflibercept injections with at least 5 years of follow-up. All of them received 3 monthly injections at the loading phase, followed by an observation period, then treated with an individualized treat-and-extend regimen. Visual acuity (VA) measurement and optical coherence tomography were performed at each visit.<br><br>RESULTS: Forty-eight eyes were included. Of these, 30 were followed up for 5 years. The mean follow-up was 61.7 &#xb1; 2.3 months. The mean age was 81 &#xb1; 8 years. The visual gain was 7.3 &#xb1; 12.7 letters at 1 year, 6.5 &#xb1; 12.5 letters at 2 years, 5.2 &#xb1; 17 letters at 3 years, 6.2 &#xb1; 18.6 letters at 4 years, and 5.6 &#xb1; 20 letters at 5 years. At the last observation, 53% of eyes had VA > 70 letters. A complete fluid resolution was obtained in 53% of the eyes. At the 5-year endpoint, the total number of injections was 21.6 &#xb1; 13.4. Macular atrophy was observed in 18 eyes (60%) and subretinal fibrosis in 14 eyes (46%).<br><br>CONCLUSION: Patients with exudative AMD can maintain their visual function at 5 years with aflibercept using an individualized treatment. The loss of visual gain beyond 2 years could be related to the natural progression of the disease than the direct effect of anti-vascular endothelial growth injections.},
}
@article {pmid37479984,
year = {2023},
author = {Li, FF and Wang, Y and Chen, L and Chen, C and Chen, Q and Xiang, L and Rao, FQ and Shen, LJ and Zheng, QX and Yi, Q and Huang, XF},
title = {Causal effects of serum lipid biomarkers on early age-related macular degeneration using Mendelian randomization.},
journal = {Genes &amp; nutrition},
volume = {18},
number = {1},
pages = {11},
pmid = {37479984},
issn = {1555-8932},
support = {82201229//National Natural Science Foundation of China/ ; LY21H180004//Zhejiang Province Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear.<br><br>METHODS: In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs&#x2009;=&#x2009;11,304,110).<br><br>RESULTS: MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR&#x2009;=&#x2009;1.25, 95% CI: 1.15-1.35, P&#x2009;=&#x2009;2.61&#x2009;&#xd7;&#x2009;10[-8]). In addition, level of ApoA is also positively associated with risk of early AMD (OR&#x2009;=&#x2009;2.04, 95% CI: 1.50-2.77, P&#x2009;=&#x2009;6.27&#x2009;&#xd7;&#x2009;10[-6]). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR&#x2009;=&#x2009;0.77, 95% CI: 0.71-0.84, P&#x2009;=&#x2009;5.02&#x2009;&#xd7;&#x2009;10[-10]). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results.<br><br>CONCLUSION: This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.},
}
@article {pmid37479063,
year = {2023},
author = {Zhang, Y and Zhang, XJ and Yuan, N and Wang, YM and Ip, P and Chen, LJ and Tham, CC and Pang, CP and Yam, JC},
title = {Secondhand smoke exposure and ocular health: A systematic review.},
journal = {Survey of ophthalmology},
volume = {68},
number = {6},
pages = {1166-1207},
doi = {10.1016/j.survophthal.2023.07.001},
pmid = {37479063},
issn = {1879-3304},
mesh = {Humans ; *Tobacco Smoke Pollution/adverse effects ; Eye ; *Macular Degeneration ; *Conjunctivitis ; },
abstract = {The toxicology of secondhand smoke (SHS), along with the harm of its exposure to human health, has been generally acknowledged; however, specific evidence is lacking on the association between SHS exposure and ocular health. In this systematic review (PROSPERO registration number: CRD42022247992), we included 55 original articles published by 12 May 2023, which dealt with SHS exposure and ocular disorders, such as eye irritation, conjunctivitis, dry eye diseases, uveitis, myopia, astigmatism, contact lens discomfort, age-related macular degeneration, glaucoma, and thyroid eye disease that addressed the ocular neurovascular structures of the macular, retinal nerve fiber layer, choroid, and corneal biomechanical parameters. We found compelling correlational evidence for eye irritation, conjunctivitis, and dry eye symptoms-supporting that SHS exposure was positively associated with inflammatory and allergic changes in the eyes. Yet, evidence about the associations between SHS exposure and other ocular disorders, structures, and parameters is still limited or controversial. Given the limitations of existing literature, more investigations with high quality and rigorous design are warranted to elucidate the potentially harmful effects of SHS exposure on ocular health.},
}
@article {pmid37478687,
year = {2023},
author = {Hallam, TM and Sharp, SJ and Andreadi, A and Kavanagh, D},
title = {Complement factor I: Regulatory nexus, driver of immunopathology, and therapeutic.},
journal = {Immunobiology},
volume = {228},
number = {5},
pages = {152410},
doi = {10.1016/j.imbio.2023.152410},
pmid = {37478687},
issn = {1878-3279},
support = {/WT_/Wellcome Trust/United Kingdom ; /MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Complement Factor I/chemistry ; Complement C3/genetics ; *Atypical Hemolytic Uremic Syndrome ; Mutation ; Inflammation ; Complement C3b ; },
abstract = {Complement factor I (FI) is the nexus for classical, lectin and alternative pathway complement regulation. FI is an 88 kDa plasma protein that circulates in an inactive configuration until it forms a trimolecular complex with its cofactor and substrate whereupon a structural reorganization allows the catalytic triad to cleave its substrates, C3b and C4b. In keeping with its role as the master complement regulatory enzyme, deficiency has been linked to immunopathology. In the setting of complete FI deficiency, a consumptive C3 deficiency results in recurrent infections with encapsulated microorganisms. Aseptic cerebral inflammation and vasculitic presentations are also less commonly observed. Heterozygous mutations in the factor I gene (CFI) have been demonstrated to be enriched in atypical haemolytic uraemic syndrome, albeit with a very low penetrance. Haploinsufficiency of CFI has also been associated with decreased retinal thickness and is a strong risk factor for the development of age-related macular degeneration. Supplementation of FI using plasma purified or recombinant protein has long been postulated, however, technical difficulties prevented progression into clinical trials. It is only using gene therapy that CFI supplementation has reached the clinic with GT005 in phase I/II clinical trials for geographic atrophy.},
}
@article {pmid37478270,
year = {2023},
author = {Qi, Y and Cui, L and Zhang, L and Yan, C and Jiang, Y and Ye, S and Ji, L and Qiu, Y and Zhang, L},
title = {Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves.},
journal = {Medicine},
volume = {102},
number = {29},
pages = {e34210},
pmid = {37478270},
issn = {1536-5964},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy ; Vascular Endothelial Growth Factor A/therapeutic use ; *Retinal Vein Occlusion/drug therapy/chemically induced ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Vascular Endothelial Growth Factors/therapeutic use ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P < .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.},
}
@article {pmid37477986,
year = {2024},
author = {Vosoughi, AR and Donaldson, L and Micieli, JA and Margolin, EA},
title = {Maculopathies Referred to Neuro-Ophthalmology Clinic as Optic Neuropathies: A Case Series.},
journal = {Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society},
volume = {44},
number = {3},
pages = {355-359},
doi = {10.1097/WNO.0000000000001950},
pmid = {37477986},
issn = {1536-5166},
mesh = {Humans ; Female ; Male ; Middle Aged ; Adult ; Aged ; Adolescent ; Retrospective Studies ; *Optic Nerve Diseases/diagnosis ; Aged, 80 and over ; Young Adult ; Tomography, Optical Coherence/methods ; Diagnosis, Differential ; Referral and Consultation ; Visual Acuity/physiology ; Ophthalmology ; Neurology ; },
abstract = {BACKGROUND: The clinical features of maculopathies and optic neuropathies often overlap: Both present with decreased visual acuity and variable loss of color vision; thus, maculopathy can be misdiagnosed as optic neuropathy, leading to patient harm. We aimed to determine what findings and/or tests were most helpful in differentiating between optic neuropathy and maculopathy.<br><br>METHODS: A retrospective chart review of consecutive patients over 4.5 years who were referred to neuro-ophthalmology clinics with the diagnosis of optic neuropathy but whose final diagnosis was maculopathy. Patient demographics, mode of presentation, clinical profile, complete ophthalmological examination, results of all ancillary testing, and final diagnosis were recorded.<br><br>RESULTS: A total of 47 patients (27 women) were included. The median age was 55 years (range, 18-85). Most referrals were by ophthalmologists (72.3%) and optometrists (12.8%). The diagnosis of maculopathy was made in 51.1% of patients at the time of first neuro-ophthalmic consultation. Only 6.4% patients (3) had relative afferent pupillary defect. Benign disc anomalies (tilted, myopic, small, or anomalous discs) were present in 34.0%, and 21.3% had pathologic disc changes unrelated or secondary to maculopathy. Macular ocular coherence tomography (OCT) was abnormal in 84.4% (with outer retinal pathology in 42.2% and inner retina pathology in 17.8%). Retinal nerve fiber layer (RNFL) thickness was normal in 82.6% of patients.<br><br>CONCLUSIONS: Macular OCT is a high-yield test in differentiating between optic neuropathy and maculopathy and should be obtained in patients with suspected optic neuropathies who have normal RNFL thickness. Macular dystrophies, particularly cone dystrophies, unspecified retinal disorders, and macular degeneration were the most common mimics of optic neuropathy. The diagnosis was often present on OCT of the macula. The presence of coexistent benign and pathological disc anomalies may lead to maculopathy being misdiagnosed as optic neuropathy.},
}
@article {pmid37477933,
year = {2023},
author = {Higgins, BE and Montesano, G and Dunbar, HMP and Binns, AM and Taylor, DJ and Behning, C and Abdirahman, A and Schmid, MC and Terheyden, JH and Zakaria, N and Poor, S and Finger, RP and Leal, S and Holz, FG and Rubin, GS and Luhmann, UFO and Crabb, DP and , },
title = {Test-Retest Variability and Discriminatory Power of Measurements From Microperimetry and Dark Adaptation Assessment in People With Intermediate Age-Related Macular Degeneration - A MACUSTAR Study Report.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {7},
pages = {19},
pmid = {37477933},
issn = {2164-2591},
mesh = {Humans ; Dark Adaptation ; *Visual Field Tests ; Cross-Sectional Studies ; *Macular Degeneration ; },
abstract = {PURPOSE: The purpose of this study was to assess test-retest variability and discriminatory power of measures from macular integrity assessment (S-MAIA) and AdaptDx.<br><br>METHODS: This is a cross-sectional study of 167 people with intermediate age-related macular degeneration (iAMD), no AMD (controls; n = 54), early AMD (n = 28), and late AMD (n = 41), recruited across 18 European ophthalmology centers. Repeat measures of mesopic and scotopic S-MAIA average (mean) threshold (MMAT decibels [dB] and SMAT [dB]) and rod intercept time (RIT [mins]) at 2 visits 14 (&#xb1;7) days apart were recorded. Repeat measures were assessed by Bland-Altman analysis, intra-class correlation coefficients (ICCs) and variability ratios. Secondary analysis assessed the area under the receiver operating characteristic curves (AUC) to determine the ability to distinguish people as having no AMD, early AMD, or iAMD.<br><br>RESULTS: Data were available for 128, 131, and 103 iAMD participants for the mesopic and scotopic S-MAIA and AdaptDx, respectively. MMAT and SMAT demonstrate similar test-retest variability in iAMD (95% confidence interval [CI] ICC of 0.79-0.89 and 0.78-0.89, respectively). ICCs were worse in RIT (95% CI ICC = 0.55-0.77). All tests had equivalent AUCs (approximately 70%) distinguishing between subjects with iAMD and controls, whereas early AMD was indistinguishable from iAMD on all measures (AUC = <55%). A learning effect was not seen in these assessments under the operating procedures used.<br><br>CONCLUSIONS: MMAT, SMAT, and RIT have adequate test-retest variability and are all moderately good at separating people with iAMD from controls.<br><br>TRANSLATIONAL RELEVANCE: Expected levels of test-retest variability and discriminatory power of the AdaptDx and MAIA devices in a clinical study setting must be considered when designing future trials for people with AMD.},
}
@article {pmid37477856,
year = {2023},
author = {Patel, PJ and Villavicencio, P and Hanumunthadu, D},
title = {Systematic Review of Neovascular Age-Related Macular Degeneration Disease Activity Criteria Use to Shorten, Maintain or Extend Treatment Intervals with Anti-VEGF in Clinical Trials: Implications for Clinical Practice.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2323-2346},
pmid = {37477856},
issn = {2193-8245},
abstract = {INTRODUCTION: Clinical trials in neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor (ant-VEGF) injections use disease activity (DA) criteria to shorten, maintain or increase the interval between injections. Differences in these DA criteria may contribute to differences in the proportions of patients with macular fluid at key time points or achieving extended dosing intervals in these trials. We identified, collated and evaluated DA criteria from pivotal anti-VEGF nAMD trials to understand how differences impact on these studies and real-world visual acuity and extending dosing outcomes.<br><br>METHODS: This was a systematic review of literature on Pubmed for randomised clinical trials in nAMD using a proactive treatment regimen. We excluded case reports, review articles and studies on fewer than 50 participants.<br><br>RESULTS: Twelve clinical trials (LUCAS, VIEW, TREX-AMD, FLUID, TREND, RIVAL, ALTAIR, CANTREAT, ARIES, TREX-Conbercept, HAWK &amp; HARRIER, TENAYA &amp; LUCERNE) investigating anti-VEGF treatment of nAMD were identified according to our search strategy. Different studies utilised a different combination of DA criteria. Specifically, six trials included visual acuity change; four included macular thickness change; one included visual acuity change if associated with macular thickness change; one with qualitative optical coherence tomography (OCT) features; four with qualitative OCT features if also associated with visual acuity change; 10 with macular haemorrhage and five with other fluorescein angiographic features.<br><br>CONCLUSION: Different clinical trials use different DA criteria when altering the interval between anti-VEGF injections. This makes it difficult to draw meaningful conclusions about secondary outcomes such as proportion of patients treated at extended dosing intervals or proportions of eyes with persistent subretinal or intraretinal fluid. Standardising DA criteria in clinical trials and preferentially using those easily applied in a real-world setting would lead to results more achievable in real-world settings and for a meaningful comparison of treatment durability.},
}
@article {pmid37474015,
year = {2023},
author = {Jakobsen, TS and Fabian-Jessing, BK and Hansen, S and Bek, T and Askou, AL and Corydon, TJ},
title = {Porcine models of choroidal neovascularization: A systematic review.},
journal = {Experimental eye research},
volume = {234},
number = {},
pages = {109590},
doi = {10.1016/j.exer.2023.109590},
pmid = {37474015},
issn = {1096-0007},
mesh = {Female ; Humans ; Swine ; Animals ; Disease Models, Animal ; *Choroidal Neovascularization/drug therapy ; Retina/pathology ; Bruch Membrane/pathology ; Fluorescein Angiography ; },
abstract = {Animal models of choroidal neovascularization (CNV) are extensively used in translational studies of CNV formation and to evaluate angiostatic treatment strategies. However, the current paucity of large animal models compared with rodent models constitutes a knowledge gap regarding the clinical translation of findings. Ocular anatomical and physiological similarities to humans suggest the pig as a relevant model animal. Thus, a systematic survey of porcine CNV models was performed to identify pertinent model parameters and suggest avenues for model standardization and optimization. A systematic search was performed in PubMed and EMBASE on November 28, 2022 for porcine models of CNV. Following inclusion by two investigators, data from the articles were extracted according to a predefined protocol. A total of 14 articles, representing 19 independent porcine CNV models were included. The included models were almost equally divided between laser-induced (53%) and surgically-induced (47%) models. Different specified breeds of domestic pigs (71%) were most commonly used in the studies. All studies used normal animals. Female pigs were reported used in 43% of the studies, while 43% did not report on sex of the animals. Younger pigs were typically used. The surgical models reported consistent CNV induction following mechanical Bruch's membrane rupture. The laser models used variants of the infrared diode laser (40%) or the frequency-doubled Nd:YAG laser (50%). Both lasers enabled successful CNV induction with reported induction rates ranging from 60 to 100%. Collateral damage to the neuroretina was reported for the infrared diode laser. CNV evaluation varied across studies with fluorescein angiography (50%) as the most used in vivo method and retinal sections (71%) as the most used ex vivo method. In interventional studies, quantification of lesions was in general performed between 7 and 14 days. The field of porcine CNV models is relatively small and heterogeneous and almost equally divided between surgically-induced and laser-induced models. Both methods have allowed successful modeling of CNV formation with induction rates comparable to those of non-human primates. However, the field would benefit from standardization of model parameters and reporting. This includes laser parameters and validation of CNV formation as well as methods of CNV evaluation and statistical analysis.},
}
@article {pmid37471073,
year = {2023},
author = {Grigsby, D and Klingeborn, M and Kelly, U and Chew, LA and Asokan, A and Devlin, G and Smith, S and Keyes, L and Timmers, A and Scaria, A and Bowes Rickman, C},
title = {AAV Gene Augmentation of Truncated Complement Factor H Differentially Rescues Ocular Complement Dysregulation in a Mouse Model.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {10},
pages = {25},
pmid = {37471073},
issn = {1552-5783},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; T32 GM007171/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; *Complement Factor H/genetics/metabolism ; Liver/metabolism ; *Macular Degeneration/genetics ; Polymorphism, Single Nucleotide ; Retina/metabolism ; Mice, Knockout ; },
abstract = {PURPOSE: Complement dysregulation in the eye has been implicated in the pathogenesis of age-related macular degeneration (AMD), and genetic variants of complement factor H (CFH) are strongly associated with AMD risk. We therefore aimed to untangle the role of CFH and its splice variant, factor H-like 1 (FHL-1), in ocular complement regulation derived from local versus circulating sources. We assessed the therapeutic efficacy of adeno-associated viruses (AAVs) expressing human FHL-1 and a truncated version of CFH (tCFH), which retains the functional N- and C-terminal ends of the CFH protein, in restoring the alternative complement pathway in Cfh-/- mouse eyes and plasma.<br><br>METHODS: Using Cfh-/- mice as a model of complement dysregulation, AAV vectors expressing tCFH or FHL-1 were injected subretinally or via tail vein, and the efficacy of the constructs was evaluated.<br><br>RESULTS: Following subretinal injections, tCFH expression rescued factor B (FB) retention in the eye, but FHL-1 expression did not. By contrast, both constructs restored FB detection in plasma following tail vein injections. Both tCFH and FHL-1 proteins accumulated in the posterior eyecup from the circulation following liver transduction; however, neither was able to significantly regulate local ocular complement.<br><br>CONCLUSIONS: Our findings demonstrate that the C-terminus of human CFH is necessary for complement regulation in the murine eye. Furthermore, exogenous CFH must be synthesized locally to maximize complement regulation in the retina. These findings establish a critical foundation for development of CFH augmentation-based gene therapies for the eye.},
}
@article {pmid37469309,
year = {2023},
author = {Wang, H},
title = {microRNA pathological mechanisms between Parkinson's disease, Alzheimer's disease, glaucoma and macular degeneration.},
journal = {Expert reviews in molecular medicine},
volume = {25},
number = {},
pages = {e24},
doi = {10.1017/erm.2023.19},
pmid = {37469309},
issn = {1462-3994},
abstract = {Reactive oxygen species (ROS) play an essential role in regulating various functions of organisms such as gene transcription, signalling transduction and immune response. However, overproduction of ROS can lead to oxidative stress, which is related to various ageing diseases including eye and brain degenerative diseases. Ocular measurements have recently been suggested as potential sources of biomarkers for the early detection of brain neurodegenerative diseases. MicroRNAs (miRNAs) are useful biomarkers for various diseases including degenerative diseases. miRNAs play an important role in the oxidative stress mechanisms of ageing diseases. In this paper, the role of miRNAs related to oxidative stress mechanisms in four ageing diseases, Parkinson's disease (PD), Alzheimer's disease (AD), glaucoma and age-related macular degeneration was reviewed. The common miRNA biomarkers related to the four diseases were also discussed. The results show that these eye and brain ageing diseases share many common miRNA biomarkers. It indicates that the ocular condition may be a prognostic biomarker for PD or AD patients. When a patient's eye condition changes, this can be a warning of a change in PD or AD status.},
}
@article {pmid37467881,
year = {2023},
author = {Kwa, FAA and Bui, BV and Thompson, BR and Ayton, LN},
title = {Preclinical investigations on broccoli-derived sulforaphane for the treatment of ophthalmic disease.},
journal = {Drug discovery today},
volume = {28},
number = {9},
pages = {103718},
doi = {10.1016/j.drudis.2023.103718},
pmid = {37467881},
issn = {1878-5832},
mesh = {Humans ; *Brassica ; *Retinitis Pigmentosa/therapy ; *Macular Degeneration/drug therapy ; Isothiocyanates/therapeutic use ; Vision Disorders ; },
abstract = {Vision loss causes a significant burden on individuals and communities on a financial, emotional and social level. Common causes include age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and retinitis pigmentosa (RP; also known as 'rod-cone dystrophy'). As the population continues to grow and age globally, an increasing number of people will experience vision loss. Hence, there is an urgent need to develop therapies that can curb early pathological events. The broccoli-derived compound, sulforaphane (SFN), is reported to have multiple health benefits and modes of action. In this review, we outline the preclinical findings on SFN in ocular diseases and discuss the future clinical testing of this compound.},
}
@article {pmid37467724,
year = {2023},
author = {Lo Faro, V},
title = {Answer to the Hamlet-like dilemma of lipid metabolites causing senile macular degeneration.},
journal = {Cell reports. Medicine},
volume = {4},
number = {7},
pages = {101077},
pmid = {37467724},
issn = {2666-3791},
mesh = {Humans ; *Macular Degeneration/genetics/metabolism ; Metabolomics ; Lipids ; },
abstract = {In this issue of Cell Reports Medicine, Han et al.[1] conducted a multi-ancestry genetic and metabolomic analysis to investigate the causal relationships between age-related macular degeneration and plasma and urine metabolites.},
}
@article {pmid37462980,
year = {2023},
author = {Parsons, NB and Annamalai, B and Rohrer, B},
title = {Regulatable Complement Inhibition of the Alternative Pathway Mitigates Wet Age-Related Macular Degeneration Pathology in a Mouse Model.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {7},
pages = {17},
pmid = {37462980},
issn = {2164-2591},
support = {R01 EY019320/EY/NEI NIH HHS/United States ; I01 BX003050/BX/BLRD VA/United States ; I01 RX000444/RX/RRD VA/United States ; T32 DC014435/DC/NIDCD NIH HHS/United States ; F99 NS124188/NS/NINDS NIH HHS/United States ; IK6 BX004858/BX/BLRD VA/United States ; },
mesh = {Mice ; Animals ; Humans ; Complement Pathway, Alternative/genetics ; Hydrogen Peroxide/pharmacology ; Mice, Inbred C57BL ; Disease Models, Animal ; *Choroidal Neovascularization/genetics/therapy ; *Wet Macular Degeneration/genetics/therapy ; },
abstract = {PURPOSE: Risk for developing age-related macular degeneration (AMD) is linked to an overactive complement system. In the mouse model of laser-induced choroidal neovascularization (CNV), elevated levels of complement effector molecules, including complement C3, have been identified, and the alternative pathway (AP) is required for pathology. The main soluble AP regular is complement factor H (fH). We have previously shown that AP inhibition via subretinal AAV-mediated delivery of CR2-fH using a constitutive promoter is efficacious in reducing CNV. Here we ask whether the C3 promoter (pC3) effectively drives CR2-fH bioavailability for gene therapy.<br><br>METHODS: Truncated pC3 was used to generate plasmids pC3-mCherry/CR2-fH followed by production of corresponding AAV5 vectors. pC3 activation was determined in transiently transfected ARPE-19 cells stimulated with H2O2 or normal human serum (+/- antioxidant or humanized CR2-fH, respectively). CNV was analyzed in C57BL/6J mice treated subretinally with AAV5-pC3-mCherry/CR2-fH using imaging (optical coherence tomography [OCT] and fundus imaging), functional (electroretinography [ERG]), and molecular (protein expression) readouts.<br><br>RESULTS: Modulation of pC3 in vitro is complement and oxidative stress dependent, as shown by mCherry fluorescence. AAV5-pC3-CR2-fH were identified as safe and effective using OCT and ERG. CR2-fH expression significantly reduced CNV compared to mCherry and was correlated with reduced levels of C3dg/C3d in the retinal pigment epithelium/choroid fraction.<br><br>CONCLUSIONS: We conclude that complement-dependent regulation of AP inhibition ameliorates AMD pathology as effectively as using a constitutive promoter.<br><br>TRANSLATIONAL RELEVANCE: The goal of anticomplement therapy is to restore homeostatic levels of complement activation, which might be more easily achievable using a self-regulating system.},
}
@article {pmid37461836,
year = {2024},
author = {Chronopoulos, A and Huynh, E and Ashurov, A and Schutz, JS and Jonas, JB and Hattenbach, LO},
title = {Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.},
journal = {European journal of ophthalmology},
volume = {34},
number = {2},
pages = {487-496},
doi = {10.1177/11206721231187663},
pmid = {37461836},
issn = {1724-6016},
mesh = {Humans ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Ranibizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Macular Degeneration/complications/diagnosis/drug therapy ; *Retinal Detachment/diagnosis/drug therapy/etiology ; Intravitreal Injections ; *Wet Macular Degeneration/complications/diagnosis/drug therapy ; Recombinant Fusion Proteins/therapeutic use ; *Antibodies, Monoclonal, Humanized ; },
abstract = {PURPOSE: To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies.<br><br>METHODS: In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase.<br><br>RESULTS: The study included 20 eyes of 18 consecutively treated patients (age: 77&#x2009;&#xb1;&#x2009;6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5&#x2009;&#xb1;&#x2009;0.5 logMAR vs 0.5&#x2009;&#xb1;&#x2009;0.6 logMAR) or mean CRT (320&#x2009;&#xb1;&#x2009;60 &#xb5;m vs 313&#x2009;&#xb1;&#x2009;83 &#xb5;m) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3&#x2009;&#xb1;&#x2009;0.2 logMAR, P&#x2009;<&#x2009;0.05) and CRT (264&#x2009;&#xb1;&#x2009;55 &#xb5;m, P&#x2009;<&#x2009;0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm[2] to 5.18 mm[2], P&#x2009;<&#x2009;0.05) and PED volume (0.39 mm[3] to 1.07 mm[3], P&#x2009;<&#x2009;0.05); however, both parameters improved after switching to brolucizumab (3.81 mm[2] and 0.37 mm[3], P&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.},
}
@article {pmid37461783,
year = {2023},
author = {Riazi Esfahani, P and Reddy, AJ and Thomas, J and Sommer, DA and Nguyen, A and Farasat, V and Nawathey, N and Bachir, A and Brahmbhatt, T and Patel, R},
title = {An Analysis of the Usage of Retinal Imaging Technology in the Detection of Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {15},
number = {6},
pages = {e40527},
pmid = {37461783},
issn = {2168-8184},
abstract = {Age-related macular degeneration (AMD) is a disease that worsens the central vision of numerous individuals across the globe. Ensuring that patients are diagnosed accurately and that their symptoms are carefully monitored is essential to ensure that adequate care is delivered. To accomplish this objective, retinal imaging technology is necessary to assess the pathophysiology that is required to give an accurate diagnosis of AMD. The purpose of this review is to assess the ability of various retinal imaging technologies such as optical coherence tomography (OCT), color fundus retinal photography, fluorescein angiography, and fundus photography. The statistical methods that were conducted yielded results that suggested that using OCT in conjunction with other imaging technologies results in a higher detection of symptoms among patients that have AMD. Further investigation should be conducted to ascertain the validity of the conclusions that were stated within the review.},
}
@article {pmid37459289,
year = {2023},
author = {Ruamviboonsuk, P and Ruamviboonsuk, V and Tiwari, R},
title = {Recent evidence of economic evaluation of artificial intelligence in ophthalmology.},
journal = {Current opinion in ophthalmology},
volume = {34},
number = {5},
pages = {449-458},
doi = {10.1097/ICU.0000000000000987},
pmid = {37459289},
issn = {1531-7021},
mesh = {Infant, Newborn ; Humans ; *Ophthalmology ; Artificial Intelligence ; *Diabetic Retinopathy/diagnosis ; Cost-Benefit Analysis ; Delivery of Health Care ; },
abstract = {PURPOSE OF REVIEW: Health economic evaluation (HEE) is essential for assessing value of health interventions, including artificial intelligence. Recent approaches, current challenges, and future directions of HEE of artificial intelligence in ophthalmology are reviewed.<br><br>RECENT FINDINGS: Majority of recent HEEs of artificial intelligence in ophthalmology were for diabetic retinopathy screening. Two models, one conducted in the rural USA (5-year period) and another in China (35-year period), found artificial intelligence to be more cost-effective than without screening for diabetic retinopathy. Two additional models, which compared artificial intelligence with human screeners in Brazil and Thailand for the lifetime of patients, found artificial intelligence to be more expensive from a healthcare system perspective. In the Thailand analysis, however, artificial intelligence was less expensive when opportunity loss from blindness was included. An artificial intelligence model for screening retinopathy of prematurity was cost-effective in the USA. A model for screening age-related macular degeneration in Japan and another for primary angle close in China did not find artificial intelligence to be cost-effective, compared with no screening. The costs of artificial intelligence varied widely in these models.<br><br>SUMMARY: Like other medical fields, there is limited evidence in assessing the value of artificial intelligence in ophthalmology and more appropriate HEE models are needed.},
}
@article {pmid37459045,
year = {2023},
author = {Gupta, S and Lytvynchuk, L and Ardan, T and Studenovska, H and Sharma, R and Faura, G and Eide, L and Shanker Verma, R and Znaor, L and Erceg, S and Stieger, K and Motlik, J and Petrovski, G and Bharti, K},
title = {Progress in Stem Cells-Based Replacement Therapy for Retinal Pigment Epithelium: In Vitro Differentiation to In Vivo Delivery.},
journal = {Stem cells translational medicine},
volume = {12},
number = {8},
pages = {536-552},
pmid = {37459045},
issn = {2157-6580},
support = {18-04393S/MCCC_/Marie Curie/United Kingdom ; },
mesh = {Humans ; Retinal Pigment Epithelium/metabolism ; Retina ; *Macular Degeneration/therapy/metabolism ; Cell Differentiation ; *Pluripotent Stem Cells ; },
abstract = {Retinal pigment epithelium (RPE) is a critical cell monolayer forming the blood-retina-barrier (BRB) and a permeable bridge between the choriocapillaris and the retina. RPE is also crucial in maintaining photoreceptor function and for completing the visual cycle. Loss of the RPE is associated with the development of degenerative diseases like age-related macular degeneration (AMD). To treat diseases like AMD, pluripotent stem cell-derived RPE (pRPE) has been recently explored extensively as a regenerative module. pRPE like other ectodermal tissues requires specific lineage differentiation and long-term in vitro culturing for maturation. Therefore, understanding the differentiation process of RPE could be useful for stem cell-based RPE derivation. Developing pRPE-based transplants and delivering them into the subretinal space is another aspect that has garnered interest in the last decade. In this review, we discuss the basic strategies currently employed for stem cell-based RPE derivation, their delivery, and recent clinical studies related to pRPE transplantation in patients. We have also discussed a few limitations with in vitro RPE culture and potential solutions to overcome such problems which can be helpful in developing functional RPE tissue.},
}
@article {pmid37458700,
year = {2023},
author = {Bessler, S and Soltwisch, J and Dreisewerd, K},
title = {Visualization of Differential Cardiolipin Profiles in Murine Retinal Cell Layers by High-Resolution MALDI Mass Spectrometry Imaging.},
journal = {Analytical chemistry},
volume = {95},
number = {30},
pages = {11352-11358},
doi = {10.1021/acs.analchem.3c01465},
pmid = {37458700},
issn = {1520-6882},
mesh = {Animals ; Mice ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; *Cardiolipins/analysis ; *Retina/chemistry ; Diagnostic Imaging ; Specimen Handling ; },
abstract = {The precise fatty acyl chain configuration of cardiolipin (CL), a tetrameric mitochondrial-specific membrane lipid, exhibits dependence on cell and tissue types. A powerful method to map CL profiles in tissue sections in a spatially resolved manner is matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). To build on and explore this potential, we employed a quadrupole time-of-flight mass spectrometer along with optimized sample preparation protocols. We imaged the CL profiles of individual murine retinal cell layers at a pixel size of 10 μm. In combination with tandem MS, we obtained detailed insights into the CL composition of individual retinal cell layers. In particular, we found differential expression of the polyunsaturated fatty acids (PUFA) linoleic, arachidonic, and docosahexaenoic acids. PUFAs are prone to peroxidation and hence regarded as critical factors in development and progression of retinal pathologies, such as age-related macular degeneration (AMD). The ability of MALDI-MSI to provide cues on the CL composition in neuronal tissue with close to single-cell resolution can provide important insights into retinal physiology in health and disease.},
}
@article {pmid37458693,
year = {2023},
author = {Rickabaugh, E and Weatherston, D and Harris, TI and Jones, JA and Vargis, E},
title = {Engineering a Biomimetic In Vitro Model of Bruch's Membrane Using Hagfish Slime Intermediate Filament Proteins.},
journal = {ACS biomaterials science &amp; engineering},
volume = {9},
number = {8},
pages = {5051-5061},
doi = {10.1021/acsbiomaterials.3c00411},
pmid = {37458693},
issn = {2373-9878},
support = {R15 EY028732/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Bruch Membrane/metabolism/pathology ; *Hagfishes ; Intermediate Filament Proteins/metabolism ; Biomimetics ; Pigment Epithelium of Eye/metabolism/pathology ; Biocompatible Materials ; },
abstract = {Bruch's membrane resides in the subretinal tissue and regulates the flow of nutrients and waste between the retinal pigment epithelial (RPE) and vascular layers of the eye. With age, Bruch's membrane becomes thicker, stiffer, and less permeable, which impedes its function as a boundary layer in the subretina. These changes contribute to pathologies such as age-related macular degeneration (AMD). To better understand how aging in Bruch's membrane affects surrounding tissues and to determine the relationship between aging and disease, an in vitro model of Bruch's membrane is needed. An accurate model of Bruch's membrane must be a proteinaceous, semipermeable, and nonporous biomaterial with similar mechanical properties to in vivo conditions. Additionally, this model must support RPE cell growth. While models of subretinal tissue exist, they typically differ from in vivo Bruch's membrane in one or more of these properties. This study evaluates the capability of membranes created from recombinant hagfish intermediate filament (rHIF) proteins to accurately replicate Bruch's membrane in an in vitro model of the subretinal tissue. The physical characteristics of these rHIF membranes were evaluated using mechanical testing, permeability assays, brightfield microscopy, and scanning electron microscopy. The capacity of the membranes to support RPE cell culture was determined using brightfield and fluorescent microscopy, as well as immunocytochemical staining. This study demonstrates that rHIF protein membranes are an appropriate biomaterial to accurately mimic both healthy and aged Bruch's membrane for in vitro modeling of the subretinal tissue.},
}
@article {pmid37457139,
year = {2023},
author = {Madueña-Angulo, SE and Beltran-Ontiveros, SA and Leal-Leon, E and Contreras-Gutierrez, JA and Lizarraga-Verdugo, E and Gutierrez-Arzapalo, PY and Lizarraga-Velarde, S and Romo-Garcia, E and Montero-Vela, J and Moreno-Ortiz, JM and Garcia-Magallanes, N and Cuen-Diaz, HM and Magaña-Gomez, J and Velazquez, DZ and Hernandez-Carreño, PE and Jimenez-Trejo, F and Reyes, M and Muñiz, FP and Diaz, D},
title = {National sex- and age-specific burden of blindness and vision impairment by cause in Mexico in 2019: a secondary analysis of the Global Burden of Disease Study 2019.},
journal = {Lancet regional health. Americas},
volume = {24},
number = {},
pages = {100552},
pmid = {37457139},
issn = {2667-193X},
abstract = {BACKGROUND: Reliable national estimations for blindness and vision impairment are fundamental to assessing their burden and developing public health policies. However, no comprehensive analysis is available for Mexico. Therefore, in this observational study we describe the national burden of blindness and vision loss by cause and severity during 2019.<br><br>METHODS: Using public data from the Global Burden of Disease (GBD) study 2019, we present national prevalence and years lived with disability (YLDs) counts and crude and age-standardized rates (per 100,000 people) of total, severity- and cause-specific blindness and vision impairment with 95% uncertainty intervals (UIs) by sex and age group.<br><br>FINDINGS: In Mexico, the burden of blindness and vision impairment was estimated at 11.01 million (95% UI, 9.25-13.11) prevalent cases and 384.96 thousand (259.57-544.24) YLDs during 2019. Uncorrected presbyopia caused the highest burden (6.06 million cases, 4.36-8.08), whereas severe vision loss and blindness affected 619.40 thousand (539.40-717.73) and 513.84 thousand (450.59-570.98) people, respectively. Near vision loss and refraction disorders caused 78.7% of the cases, whereas neonatal disorders and age-related macular degeneration were among the least frequent. Refraction disorders were the main cause of moderate and severe vision loss (61.44 and 35.43%), and cataracts were the second most frequent cause of blindness (26.73%). Females suffered an overall higher burden of blindness and vision impairment (54.99% and 52.85% of the total cases and YLDs), and people >50 years of age suffered the highest burden, with people between 70 and 74 years being the most affected.<br><br>INTERPRETATION: Vision loss represents a public health problem in Mexico, with women and older people being the most affected. Although the causes of vision loss contribute differentially to the severity of visual impairment, most of the impairment is avoidable. Consequently, a concerted effort at different levels is needed to alleviate this burden.<br><br>FUNDING: This study received no funding.},
}
@article {pmid37455795,
year = {2023},
author = {Erginturk Acar, D and Batioglu, F and Idil, A and Sahli, E and Goksuluk, D},
title = {Rehabilitation Methods for Patients with Geographic Atrophy due to Age-Related Macular Degeneration and Effects of Rehabilitation on Quality of Life.},
journal = {Journal of ophthalmology},
volume = {2023},
number = {},
pages = {3389750},
pmid = {37455795},
issn = {2090-004X},
abstract = {PURPOSE: The purpose of the study is to evaluate the low vision rehabilitation methods and to investigate the effect of visual rehabilitation on quality of life in patients with low vision due to geographic atrophy from age-related macular degeneration (ARMD).<br><br>METHODS: The better-seeing eye of 78 patients with geographic atrophy due to ARMD were included in the study. Sociodemographic characteristics, ophthalmological examination findings, and preferred low vision aids for near and distant were recorded. Fifty-seven patients who preferred to use a low vision aid device in daily life were considered as a rehabilitation group, whereas 21 patients who did not use any device were considered as a control group. The National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was applied to all patients at the initial examination and at least 6&#x2009;months after the initial examination.<br><br>RESULTS: In the rehabilitation group, statistically significant increases were found in the overall composite score, and general vision, near and distance activities, social functioning, mental health, role difficulties, and dependency subscale scores of the NEI-VFQ-25 quality of life scale after low vision rehabilitation (p=0.009 for general vision, p < 0.001; for others). In the control group, there was no statistically significant change in any of the subscale scores or the overall score of the scale (p > 0.05). All patients (n&#x2009;=&#x2009;78) were recommended to use at least one low vision aid for near vision. Hyperocular glasses were recommended for 77 patients (98.72%), magnifiers for 15 patients (19.23%), electro-optical devices for 2 patients (2.56%), and telemicroscope for one patient (1.28%). Furthermore, 17 patients (21.8%) were prescribed more than one low vision aids. However, for distance vision, only 29 patients (37.18%) received a recommendation for a low vision aid.<br><br>CONCLUSIONS: Low vision patients with ARMD-related geographic atrophy should meet with low vision aids as soon as possible and should be included in low vision rehabilitation programs.},
}
@article {pmid37454969,
year = {2023},
author = {Jiménez-Loygorri, JI and Benítez-Fernández, R and Viedma-Poyatos, &#xc1; and Zapata-Muñoz, J and Villarejo-Zori, B and Gómez-Sintes, R and Boya, P},
title = {Mitophagy in the retina: Viewing mitochondrial homeostasis through a new lens.},
journal = {Progress in retinal and eye research},
volume = {96},
number = {},
pages = {101205},
doi = {10.1016/j.preteyeres.2023.101205},
pmid = {37454969},
issn = {1873-1635},
mesh = {Mice ; Animals ; *Mitophagy/physiology ; *Retina/metabolism ; Retinal Ganglion Cells/metabolism ; Autophagy ; Mitochondria/metabolism ; Homeostasis ; },
abstract = {Mitochondrial function is key to support metabolism and homeostasis in the retina, an organ that has one of the highest metabolic rates body-wide and is constantly exposed to photooxidative damage and external stressors. Mitophagy is the selective autophagic degradation of mitochondria within lysosomes, and can be triggered by distinct stimuli such as mitochondrial damage or hypoxia. Here, we review the importance of mitophagy in retinal physiology and pathology. In the developing retina, mitophagy is essential for metabolic reprogramming and differentiation of retina ganglion cells (RGCs). In basal conditions, mitophagy acts as a quality control mechanism, maintaining a healthy mitochondrial pool to meet cellular demands. We summarize the different autophagy- and mitophagy-deficient mouse models described in the literature, and discuss the potential role of mitophagy dysregulation in retinal diseases such as glaucoma, diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration. Finally, we provide an overview of methods used to monitor mitophagy in vitro, ex vivo, and in vivo. This review highlights the important role of mitophagy in sustaining visual function, and its potential as a putative therapeutic target for retinal and other diseases.},
}
@article {pmid37454471,
year = {2023},
author = {Nguyen, H and Di Tanna, GL and Do, V and Mitchell, P and Liew, G and Keay, L},
title = {15-year incidence of driving cessation and associated risk factors: The Blue Mountains Eye Study.},
journal = {Maturitas},
volume = {177},
number = {},
pages = {107796},
doi = {10.1016/j.maturitas.2023.107796},
pmid = {37454471},
issn = {1873-4111},
mesh = {Male ; Humans ; Female ; Incidence ; Australia ; Visual Acuity ; *Cataract ; Risk Factors ; *Macular Degeneration ; },
abstract = {OBJECTIVES: To report the 15-year incidence of driving cessation and its associated vision-related risk factors in an older Australian population-based cohort.<br><br>STUDY DESIGN: 15-year data from a sample of 2379 participants who indicated that they were driving at baseline from The Blue Mountains Eye Study was analysed. Questions about driving cessation was asked at all four visits and was recorded as a binary response (Yes/No). Clinical vision examinations were performed at each visit to determine presenting and best-corrected visual acuity and any incident eye diseases (Yes/No).<br><br>MAIN OUTCOME MEASURES: The cumulative 15-year incidence of driving cessation was calculated using interval-censored data progression-free survival analyses. Age- and sex-adjusted and multivariable-adjusted interval-censored Cox proportional hazard models were used to report the hazard ratios (HRs) for associations of baseline and incident vision status with driving cessation.<br><br>RESULTS: The 15-year cumulative incidence of driving cessation amongst the 2379 participants was 20.7&#xa0;%, with women more likely to cease driving than men (p&#xa0;=&#xa0;0.0005). Cataract (HR 1.98 (95&#xa0;% confidence interval(Cl) 1.45-2.71)) and age-related macular degeneration (HR 1.85 (95%Cl 1.37-2.50)) were associated with increased risk of driving cessation whilst presenting and best-corrected visual acuity in the better eye were protective against cessation (presenting: HR 0.96 (95%Cl 0.95-0.98); best-corrected: HR 0.93 (95%Cl 0.91-0.95)) in age- and sex-adjusted models, with these factors remaining independently associated in the multivariable-adjusted models.<br><br>CONCLUSION: Cumulative incidence of driving cessation increased with older age and was higher in females. Cataract and age-related macular degeneration were independently associated with cessation, whilst better visual acuity at baseline helped prolong driving.},
}
@article {pmid37453472,
year = {2024},
author = {Akhlaq, A and Williams, D and Clark, WL and Khan, H and Khanani, AM and Walden, L and Awh, C and Graff, JT and Graff, JM and Wakabayashi, T and Regillo, C and Maass, KF and Callaway, NF and Gune, S and Campochiaro, PA},
title = {Exudation in Patients With Neovascular Age-Related Macular Degeneration Treated With the Port Delivery System or Monthly Injections.},
journal = {American journal of ophthalmology},
volume = {258},
number = {},
pages = {158-172},
doi = {10.1016/j.ajo.2023.07.003},
pmid = {37453472},
issn = {1879-1891},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Macular Degeneration/diagnosis/drug therapy ; Retrospective Studies ; Tomography, Optical Coherence ; *Wet Macular Degeneration/diagnosis/drug therapy ; Randomized Controlled Trials as Topic ; },
abstract = {PURPOSE: To evaluate for the presence, severity, and type of exudation at each study visit for a subgroup of patients with neovascular age-related macular degeneration from the Archway and Portal trials.<br><br>DESIGN: Retrospective analysis of prospectively obtained data.<br><br>METHODS: Spectral-domain optical coherence tomography scans from each study visit of 44 patients from the Port Delivery System (PDS) arm and 32 patients from the monthly injection arm of Archway were evaluated, and composites of horizontal scans through the fovea were created. Each composite was graded for the presence, type, and severity of exudation and impact on best-corrected visual acuity.<br><br>RESULTS: After PDS implantation, 20 of 44 eyes (45%) never showed any exudation in the fovea, 2 (5%) never showed exudation in the fovea but had several missed visits, whereas 15 (34%), 3 (7%), and 4 (9%) showed mild, moderate, or severe exudation at 1 or more study visits, respectively. When exudation was present, it was most commonly subretinal fluid (50%). Of 32 patients randomized to monthly injections, 15 (47%) had no exudation in the fovea during monthly injections or after PDS implantation. Fluctuation of exudation in the fovea over time was seen in some patients after PDS implantation or during monthly injections with little or no identifiable impact on best-corrected visual acuity. In the 7 eyes with moderate or severe exudation in the fovea after PDS implantation, final vision was good in 5 (20/25 in 3, 20/40 in 1, and 20/50 in 1) and 2 had reduced vision from submacular hemorrhage.<br><br>CONCLUSIONS: The PDS provides excellent control of exudation in the fovea in patients with neovascular age-related macular degeneration, and when exudation occurs, it often resolves without a negative impact on vision.},
}
@article {pmid37452726,
year = {2023},
author = {Singh, R and Yang, X},
title = {A review on photo-mediated ultrasound therapy.},
journal = {Experimental biology and medicine (Maywood, N.J.)},
volume = {248},
number = {9},
pages = {775-786},
pmid = {37452726},
issn = {1535-3699},
support = {R01 EY029489/EY/NEI NIH HHS/United States ; R41 EB030875/EB/NIBIB NIH HHS/United States ; },
mesh = {Animals ; Rabbits ; *Ultrasonic Therapy/methods ; Ultrasonography ; Microvessels ; Veins ; *Vascular Diseases ; Microbubbles ; },
abstract = {Photo-mediated ultrasound therapy (PUT) is a novel therapeutic technique based on the combination of ultrasound and laser. The underlying mechanism of PUT is the enhanced cavitation effect inside blood vessels. The enhanced cavitation activity can result in bio-effects such as reduced perfusion in microvessels. The reduced perfusion effect in microvessels in the eye has the potential to control the progression of eye diseases such as diabetic retinopathy and age-related macular degeneration. Several in vivo studies have demonstrated the feasibility of PUT in removing microvasculature in the eye using rabbit eye model and vasculature in the skin using rabbit ear model. Numerical studies using a bubble dynamics model found that cavitation is enhanced during PUT due to the dramatic increase in size of air/vapor nuclei in blood. In addition, the study conducted to model cavitation dynamics inside a blood vessel during PUT found stresses induced on the vessel wall during PUT are higher than that at normal physiological levels, which may be responsible for bio-effects. The concentration of vasodilators such as nitric oxide and prostacyclin were also found to be affected during PUT in an in vitro study, which may limit blood perfusion in vessels. The main advantage of PUT over conventional techniques is non-invasive, precise, and selective removal of microvessels with high efficiency at relatively low energy levels of ultrasound and laser, without affecting the nearby structures. However, the main limitation of vessel rupture/hemorrhage needs to be overcome through the development of real-time monitoring of treatment effects during PUT. In addition to the application in removing microvessels, PUT-based techniques were also explored in treating other diseases. Studies have found a combination of ultrasound and laser to be effective in removing blood clots inside veins, which has the potential to treat deep-vein thrombosis. The disruption of atherosclerotic plaque using combined ultrasound and laser was also tested, and the feasibility was demonstrated.},
}
@article {pmid37452694,
year = {2023},
author = {Moir, J and Aggarwal, S and Skondra, D},
title = {Repurposing medications for treatment of age-related macular degeneration: Insights from novel approaches to data mining.},
journal = {Experimental biology and medicine (Maywood, N.J.)},
volume = {248},
number = {9},
pages = {798-810},
pmid = {37452694},
issn = {1535-3699},
mesh = {Humans ; Prospective Studies ; Drug Repositioning ; *Macular Degeneration/drug therapy/prevention &amp; control ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Levodopa/therapeutic use ; Data Mining ; },
abstract = {The economic and visual burdens associated with age-related macular degeneration (AMD) are expected to significantly increase in the coming years. As of now, interventions to delay or prevent AMD are limited. Hence, there is an urgent and unmet need to expand our therapeutic tools for AMD in a manner, that is, both efficient and cost-effective. In this review, we consider the idea of drug repurposing, in which existing medications with other indications can be re-imagined for treating AMD. We detail the results of several population-level studies that have shown associations between several candidates and decreased risk of AMD development or progression. Such candidates include the more extensively studied metformin and statins, in addition to recently identified candidates fluoxetine and l-DOPA (levodopa) that show promise. We then briefly explore results from an advanced bioinformatics study, which provides further evidence that existing medications are associated with AMD risk genes. Many of these candidates warrant further study in prospective, clinical trials, where their potential causal relationships with AMD can be thoroughly assessed.},
}
@article {pmid37452068,
year = {2023},
author = {Yeom, H and Kwon, HJ and Kim, YJ and Lee, J and Yoon, YH and Lee, JY},
title = {Real-world study to evaluate the efficacy and safety of intravitreal brolucizumab for refractory neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {11400},
pmid = {37452068},
issn = {2045-2322},
mesh = {Humans ; Ranibizumab/adverse effects ; Angiogenesis Inhibitors/adverse effects ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; },
abstract = {This retrospective study evaluated the real-world safety and effectiveness of switching to intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). A total of 81 patients who received brolucizumab injections as switch therapy were followed for more than 3 months. A good response was defined as better anatomical improvement or extended injection intervals compared with previous anti-vascular endothelial growth factor (VEGF) treatment over a mean follow-up period of 41.4 weeks. Approximately 82.7% of patients showed a good response after switching. After 1 year, patients showed significant visual gains (+ 6.6 letters, p = 0.006) and central retinal thickness reductions (- 112.6 µm, p < 0.001), with 30.8% having injection intervals extended over 12 weeks. In the poor-response group, visual acuity and anatomical outcomes worsened soon after switching. More previous injections, thinner baseline central retina, and the presence of prechoroidal cleft or polypoidal lesion resulted in a better response (p < 0.05). Adverse effects occurred in eight eyes (9.9%), including one retinal vascular occlusion and seven intraocular inflammation cases, which were unrelated to the response. Most patients with nAMD refractory to anti-VEGF treatment demonstrated anatomical improvement or extended injection intervals after switching. This study shows that identified structural biomarkers may predict treatment response and select an appropriate therapeutic strategy.},
}
@article {pmid37451546,
year = {2023},
author = {Abbadessa, A and Nuñez Bernal, P and Buttitta, G and Ronca, A and D'Amora, U and Zihlmann, C and Stiefel, N and Ambrosio, L and Malda, J and Levato, R and Crecente-Campo, J and Alonso, MJ},
title = {Biofunctionalization of 3D printed collagen with bevacizumab-loaded microparticles targeting pathological angiogenesis.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {360},
number = {},
pages = {747-758},
doi = {10.1016/j.jconrel.2023.07.017},
pmid = {37451546},
issn = {1873-4995},
mesh = {Humans ; Bevacizumab ; *Vascular Endothelial Growth Factor A/metabolism ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry ; *Neovascularization, Pathologic/drug therapy ; Human Umbilical Vein Endothelial Cells ; Collagen ; Printing, Three-Dimensional ; },
abstract = {Pathological angiogenesis is a crucial attribute of several chronic diseases such as cancer, age-related macular degeneration, and osteoarthritis (OA). In the case of OA, pathological angiogenesis mediated by the vascular endothelial growth factor (VEGF), among other factors, contributes to cartilage degeneration and to implants rejection. In line with this, the use of the anti-VEGF bevacizumab (BVZ) has been shown to prevent OA progression and support cartilage regeneration. The aim of this work was to functionalize a medical grade collagen with poly (lactic-co-glycolic acid) (PLGA) microparticles containing BVZ via three-dimensional (3D) printing to target pathological angiogenesis. First, the effect of several formulation parameters on the encapsulation and release of BVZ from PLGA microparticles was studied. Then, the anti-angiogenic activity of released BVZ was tested in a 3D cell model. The 3D printability of the microparticle-loaded collagen ink was tested by evaluating the shape fidelity of 3D printed structures. Results showed that the release and the encapsulation efficiency of BVZ could be tuned as a function of several formulation parameters. In addition, the released BVZ was observed to reduce vascularization by human umbilical vein endothelial cells. Finally, the collagen ink with embedded BVZ microparticles was successfully printed, leading to shape-stable meniscus-, nose- and auricle-like structures. Taken altogether, we defined the conditions for the successful combination of BVZ-loaded microparticles with the 3D printing of a medical grade collagen to target pathological angiogenesis.},
}
@article {pmid37451248,
year = {2023},
author = {Šalková Kráľová, J and Kolář, P and Kapounová, Z and Veselý, P and Derflerová Brázdová, Z},
title = {Dietary habits and dietary nutrient intake in patients with age-related macular degeneration: A case-control study.},
journal = {Central European journal of public health},
volume = {31},
number = {2},
pages = {140-143},
pmid = {37451248},
issn = {1210-7778},
mesh = {Male ; Humans ; Female ; Aged ; *Magnesium ; Copper ; Case-Control Studies ; Pantothenic Acid ; Quality of Life ; Diet ; Eating ; Energy Intake ; Feeding Behavior ; Zinc ; Dietary Fiber ; Fatty Acids ; Niacinamide ; *Macular Degeneration/epidemiology/chemically induced ; Riboflavin ; Vitamin B 6 ; Phosphorus ; Potassium ; Dietary Fats ; },
abstract = {OBJECTIVES: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older adults in developed countries. Although many risk factors are known, the pathogenesis of AMD is still unclear. However, oxidative stress probably plays a vital role in the process of AMD. The increasing prevalence of AMD, risk of vision loss, limited treatment of dry form, expensive treatment of wet form, and decreased quality of life are factors that lead to considering modifiable risk factors of AMD, such as nutrition. This is the first study describing the relationship between dietary habits, dietary nutrient intake and AMD in the Czech Republic.<br><br>METHODS: In this research, a total of 93 cases with AMD and 58 controls without AMD and cataracts participated. All participants were ophthalmologically examined at the Clinic of Eye Treatments at the University Hospital Brno. Data were collected using a pre-tested self-report questionnaire in a face-to-face interview. Food consumption frequency was assessed by an 18-item semiquantitative food-frequency questionnaire (FFQ). Dietary nutrient intakes were calculated from a 24-hour recall.<br><br>RESULTS: Patients with AMD compared with controls had significantly higher consumption of legumes and lower consumption of meat products, salt and salty products. In men, we found statistically significant differences in alcohol consumption. The case group consumed alcoholic beverages more frequently (median: 2 times a week) than the control group (median: 1-3 times a month). No differences in alcohol consumption were found in women. In comparison to the case group, the control group had a significantly higher dietary intake of energy (5,783.8 vs. 4,849.3 kJ/day; p = 0.002), proteins (65.3 vs. 52.3 g/day; p = 0.002), fats (57.6 vs. 49.4 g/day; p = 0.046), saturated fatty acids (21.7 vs. 18.9 g/day; p = 0.026), carbohydrates (150.4 vs. 127.1 g/day; p = 0.017), dietary fibre (13.2 vs. 11.3 g/day; p = 0.044), vitamin B2 (1.0 vs. 0.9 mg/day; p = 0.029), vitamin B3 (13.9 vs. 10.0 mg/day; p = 0.011), pantothenic acid (3.5 vs. 2.8 mg/day; p = 0.001), vitamin B6 (1.3 vs. 1.0 mg/day; p = 0.001), potassium (1,656.5 vs. 1,418.0 mg/day; p = 0.022), phosphorus (845.4 vs. 718.7 mg/day; p = 0.020), magnesium (176.5 vs. 143.0 mg/day; p = 0.012), copper (1.0 vs. 0.8 mg/day; p = 0.011), and zinc (7.1 vs. 6.1 mg/day; p = 0.012) counted from a 24-hour recall.<br><br>CONCLUSIONS: According to FFQ, dietary habits in the patients with AMD and controls were similar. In men from the case group, we found statistically significant higher alcohol consumption. According to a 24-hour recall, the controls achieved recommended dietary intakes rather than cases. In comparison to the case group, the control group had a significantly higher dietary intake of energy, proteins, fats, saturated fatty acids, carbohydrates, dietary fibre, vitamin B2, vitamin B3, pantothenic acid, vitamin B6, potassium, phosphorus, magnesium, copper, and zinc.},
}
@article {pmid37450933,
year = {2024},
author = {Sun, R and Feng, J and Wang, J},
title = {Underlying Mechanisms and Treatment of Cellular Senescence-Induced Biological Barrier Interruption and Related Diseases.},
journal = {Aging and disease},
volume = {15},
number = {2},
pages = {612-639},
pmid = {37450933},
issn = {2152-5250},
mesh = {Humans ; *Cellular Senescence ; Aging ; *Alzheimer Disease ; Dasatinib/pharmacology ; Quercetin/pharmacology ; },
abstract = {Given its increasing prevalence, aging is of great concern to researchers worldwide. Cellular senescence is a physiological or pathological cellular state caused by aging and a prominent risk factor for the interruption of the integrity and functionality of human biological barriers. Health barriers play an important role in maintaining microenvironmental homeostasis within the body. The senescence of barrier cells leads to barrier dysfunction and age-related diseases. Cellular senescence has been reported to be a key target for the prevention of age-related barrier diseases, including Alzheimer's disease, Parkinson's disease, age-related macular degeneration, diabetic retinopathy, and preeclampsia. Drugs such as metformin, dasatinib, quercetin, BCL-2 inhibitors, and rapamycin have been shown to intervene in cellular senescence and age-related diseases. In this review, we conclude that cellular senescence is involved in age-related biological barrier impairment. We further outline the cellular pathways and mechanisms underlying barrier impairment caused by cellular senescence and describe age-related barrier diseases associated with senescent cells. Finally, we summarize the currently used anti-senescence pharmacological interventions and discuss their therapeutic potential for preventing age-related barrier diseases.},
}
@article {pmid37450210,
year = {2023},
author = {Rayner, CL and Bottle, SE and Martyn, AP and Barnett, NL},
title = {Preserving Retinal Structure and Function with the Novel Nitroxide Antioxidant, DCTEIO.},
journal = {Neurochemical research},
volume = {48},
number = {11},
pages = {3402-3419},
pmid = {37450210},
issn = {1573-6903},
mesh = {Animals ; *Antioxidants/pharmacology/metabolism ; *Neurodegenerative Diseases/metabolism ; Retina/metabolism ; Nitrogen Oxides/metabolism/pharmacology ; Oxidative Stress ; Disease Models, Animal ; },
abstract = {Oxidative stress is a major contributor to progressive neurodegenerative disease and may be a key target for the development of novel preventative and therapeutic strategies. Nitroxides have been successfully utilised to study changes in redox status (biological probes) and modulate radical-induced oxidative stress. This study investigates the efficacy of DCTEIO (5,6-dicarboxy-1,1,3,3-tetraethyllisoindolin-2-yloxyl), a stable, kinetically-persistent, nitroxide-based antioxidant, as a retinal neuroprotectant. The preservation of retinal function following an acute ischaemic/reperfusion (I/R) insult in the presence of DCTEIO was quantified by electroretinography (ERG). Inflammatory responses in retinal glia were analysed by GFAP and IBA-1 immunohistochemistry, and retinal integrity assessed by histology. A nitroxide probe combined with flow cytometry provided a rapid technique to assess oxidative stress and the mitigation offered by antioxidant compounds in cultured 661W photoreceptor cells. DCTEIO protected the retina from I/R-induced damage, maintaining retinal function. Histological analysis showed preservation of retinal integrity with reduced disruption and disorganisation of the inner and outer nuclear layers. I/R injury upregulated GFAP expression, indicative of retinal stress, which was significantly blunted by DCTEIO. The number of 'activated' microglia, particularly in the outer retina, in response to cellular stress was also significantly reduced by DCTEIO, potentially suggesting reduced inflammasome activation and cell death. DCTEIO mitigated oxidative stress in 661W retinal cell cultures, in a dose-dependent fashion. Together these findings demonstrate the potential of DCTEIO as a neuroprotective therapeutic for degenerative diseases of the CNS that involve an ROS-mediated component, including those of the retina e.g. age-related macular degeneration and glaucoma.},
}
@article {pmid37449629,
year = {2023},
author = {Luo, W and Skondra, D},
title = {Implication of gut microbiome in age-related macular degeneration.},
journal = {Neural regeneration research},
volume = {18},
number = {12},
pages = {2699-2700},
pmid = {37449629},
issn = {1673-5374},
support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; },
}
@article {pmid37449599,
year = {2023},
author = {Marino, R and Sappington, R and Feligioni, M},
title = {Retinoprotective compounds, current efficacy, and future prospective.},
journal = {Neural regeneration research},
volume = {18},
number = {12},
pages = {2619-2622},
pmid = {37449599},
issn = {1673-5374},
abstract = {Retinal dysfunction is the most common cause of vision loss in several retinal disorders. It has been estimated a great increase in these pathologies that are becoming more globally widespread and numerous over time, also supported by the life expectancy increment. Among different types of retinopathies, we can account some that share causes, symptoms, and treatment including diabetic retinopathy, age-related macular degeneration, glaucoma, and retinitis pigmentosa. Molecular changes, environmental factors, and genetic predisposition might be some of the main causes that drive retinal tissue to chronic inflammation and neurodegeneration in these retinopathies. The treatments available on the market contain compounds that efficiently ameliorate some of the important clinical features of these pathologies like stabilization of the intraocular pressure, reduction of eye inflammation, control of eye oxidative stress which are considered the major molecular mechanisms related to retinal dysfunction. Indeed, the most commonly used drugs are anti-inflammatories, such as corticosteroids, antioxidant, hypotonic molecules and natural neuroprotective compounds. Unfortunately, these drugs, which are fundamental to treating disease symptoms, are not capable to cure the pathologies and so they are not life-changing for patients. This review provided an overview of current treatments on the market, but more interestingly, wants to be a quick window on the new treatments that are now in clinical trials. Additionally, it has been here highlighted that the recent technical enhancement of the investigation methods to identify the various retinopathies causes might be used as a sort of "precise medicine" approach to tailor the identification of molecular pathways involved and potentially study a dedicated treatment for each patient. This approach includes the use of cutting-edge technologies like gene therapy and metabolomics.},
}
@article {pmid37448315,
year = {2024},
author = {Tran, E and Nayeni, M and Shah, N and Malvankar-Mehta, MS},
title = {The effects of age-related macular degeneration on work productivity: A meta-analysis.},
journal = {European journal of ophthalmology},
volume = {34},
number = {3},
pages = {641-648},
pmid = {37448315},
issn = {1724-6016},
mesh = {Humans ; *Macular Degeneration ; *Efficiency ; Unemployment/statistics &amp; numerical data ; Cost of Illness ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of vision loss and blindness in older adults. Given the aging population in developed countries and the increased participation of older adults in the labour market, this paper aims to understand the impact of AMD on workplace productivity. Economic studies, comparative studies, observational studies, cohort studies, case series, randomized control trials, clinical trials, multicenter studies from MEDLINE, EMBASE, and CINHAL, as well as grey literature, were systematically searched to obtain all relevant literature. Duplicate records were removed, and two independent reviewers screened records for relevance. After screening, a risk of bias assessment was carried out. Data were extracted and a meta-analysis was performed using STATA 15.0. Fixed-effect and random-effect models were computed based on heterogeneity. Seven studies consisting of 3,060,864 subjects from 5 different countries were included in this systematic review. Mean wages lost due to impaired work productivity ranged from $1,395 to $55,180. The mean unemployment rate attributed to AMD ranged from 5.50% to 77.00%. Meta-analysis results indicated a significant unemployment rate (SMD = 0.44, CI: [0.27, 0.62]). Patients with AMD experience impaired work productivity as demonstrated by the wages lost and significantly higher rates of unemployment.},
}
@article {pmid37447632,
year = {2023},
author = {Wu, KY and Mina, M and Sahyoun, JY and Kalevar, A and Tran, SD},
title = {Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.},
journal = {Sensors (Basel, Switzerland)},
volume = {23},
number = {13},
pages = {},
pmid = {37447632},
issn = {1424-8220},
mesh = {Humans ; Quality of Life ; *Retina/pathology/physiology ; *Retinal Diseases/pathology/therapy ; *Visual Prosthesis/adverse effects/standards/trends ; *Biomedical Engineering/instrumentation/trends ; Electrodes, Implanted/standards ; Patient Selection ; Treatment Outcome ; },
abstract = {A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode-retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life.},
}
@article {pmid37447314,
year = {2023},
author = {Li, Z and Li, Y and Hou, Y and Fan, Y and Jiang, H and Li, B and Zhu, H and Liu, Y and Zhang, L and Zhang, J and Wu, M and Ma, T and Zhao, T and Ma, L},
title = {Association of Plasma Vitamins and Carotenoids, DNA Methylation of LCAT, and Risk of Age-Related Macular Degeneration.},
journal = {Nutrients},
volume = {15},
number = {13},
pages = {},
pmid = {37447314},
issn = {2072-6643},
support = {NSFC-82022062; NSFC-81973025//National Natural Science Foundation of China/ ; TY0181101//Nutrition Science Research Foundation of BY-HEALTH/ ; 2015LJXX-07//New-star Plan of Science and Technology of Shaanxi Province/ ; qngz2016004; xzy032019008; xzy022021056//the Fundamental Research Funds for the Central Universities/ ; },
mesh = {Humans ; Aged ; *Vitamins ; Carotenoids ; Vitamin A ; Phosphatidylcholine-Sterol O-Acyltransferase/genetics ; DNA Methylation ; Beta-Cryptoxanthin ; *Macular Degeneration/prevention &amp; control ; Vitamin K ; },
abstract = {Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (Pnon-linearity = 0.03). Higher concentrations of plasma retinol and β-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted β coefficient being -0.05 (95% CI: -0.08, -0.01) and -0.25 (95% CI: -0.42, -0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and β-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.},
}
@article {pmid37447310,
year = {2023},
author = {Yuan, Q and Zhu, S and Yue, S and Han, Y and Peng, G and Li, L and Sheng, Y and Wang, B},
title = {Alterations in Faecal and Serum Metabolic Profiles in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Nutrients},
volume = {15},
number = {13},
pages = {},
pmid = {37447310},
issn = {2072-6643},
support = {2021YFA1301001//National Key Research and Development Program of China/ ; 82170668//National Natural Science Foundation of China/ ; GZ1546//Sino-German Center for Research Promotion/ ; },
mesh = {Humans ; Aged ; *Metabolome ; Mass Spectrometry/methods ; Metabolomics/methods ; Chromatography, Liquid ; *Macular Degeneration ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a common and multifactorial disease in the elderly that may lead to irreversible vision loss; yet the pathogenesis of AMD remains unclear. In this study, nontargeted metabolomics profiling using ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry was applied to discover the metabolic feature differences in both faeces and serum samples between Chinese nonobese subjects with and without nAMD. In faecal samples, a total of 18 metabolites were significantly altered in nAMD patients, and metabolic dysregulations were prominently involved in glycerolipid metabolism and nicotinate and nicotinamide metabolism. In serum samples, a total of 29 differential metabolites were founded, involved in caffeine metabolism, biosynthesis of unsaturated fatty acids, and purine metabolism. Two faecal metabolites (palmitoyl ethanolamide and uridine) and three serum metabolites (4-hydroxybenzoic acid, adrenic acid, and palmitic acid) were selected as potential biomarkers for nAMD. Additionally, the significant correlations among dysregulated neuroprotective, antineuroinflammatory, or fatty acid metabolites in faecal and serum and IM dysbiosis were found. This comprehensive metabolomics study of faeces and serum samples showed that alterations in IM-mediated neuroprotective metabolites may be involved in the pathophysiology of AMD, offering IM-based nutritional therapeutic targets for nAMD.},
}
@article {pmid37446374,
year = {2023},
author = {Anitua, E and Muruzabal, F and de la Fuente, M and Del Olmo-Aguado, S and Alkhraisat, MH and Merayo-Lloves, J},
title = {PRGF Membrane with Tailored Optical Properties Preserves the Cytoprotective Effect of Plasma Rich in Growth Factors: In Vitro Model of Retinal Pigment Epithelial Cells.},
journal = {International journal of molecular sciences},
volume = {24},
number = {13},
pages = {},
pmid = {37446374},
issn = {1422-0067},
support = {ZL-2021/00557//Basque Government/ ; },
mesh = {Reactive Oxygen Species/metabolism ; *Retinal Pigment Epithelium/metabolism ; *Oxidative Stress ; Intercellular Signaling Peptides and Proteins/pharmacology/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {The present study evaluates the ability of a novel plasma rich in growth factors (PRGF) membrane with improved optical properties to reduce oxidative stress in retinal pigment epithelial cells (ARPE-19 cells) exposed to blue light. PRGF was obtained from three healthy donors and divided into four main groups: (i) PRGF membrane (M-PRGF), (ii) PRGF supernatant (S-PRGF), (iii) platelet-poor plasma (PPP) membrane diluted 50% with S-PRGF (M-PPP 50%), and (iv) M-PPP 50% supernatant (S-PPP 50%). ARPE-19 cells were exposed to blue light and then incubated with the different PRGF-derived formulations or control for 24 and 48 h under blue light exposure. Mitochondrial and cell viability, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) and ZO-1 expression were evaluated. Mitochondrial viability and cell survival were significantly increased after treatment with the different PRGF-derived formulations. ROS synthesis and HO-1 expression were significantly reduced after cell treatment with any of the PRGF-derived formulations. Furthermore, the different PRGF-derived formulations significantly increased ZO-1 expression in ARPE-19 exposed to blue light. The new PRGF membrane with improved optical properties and its supernatant (M-PPP 50% and S-PPP 50%) protected and reversed blue light-induced oxidative stress in ARPE-19 cells at levels like those of a natural PRGF membrane and its supernatant.},
}
@article {pmid37446050,
year = {2023},
author = {Songca, SP},
title = {Combinations of Photodynamic Therapy with Other Minimally Invasive Therapeutic Technologies against Cancer and Microbial Infections.},
journal = {International journal of molecular sciences},
volume = {24},
number = {13},
pages = {},
pmid = {37446050},
issn = {1422-0067},
support = {SRUG220323502//National Research Foundation/ ; LRETA24//Council for Scientific and Industrial Research/ ; },
mesh = {Humans ; Photosensitizing Agents/pharmacology/therapeutic use ; *Photochemotherapy/methods ; *Neoplasms/drug therapy ; Combined Modality Therapy ; Technology ; },
abstract = {The rapid rise in research and development following the discovery of photodynamic therapy to establish novel photosensitizers and overcome the limitations of the technology soon after its clinical translation has given rise to a few significant milestones. These include several novel generations of photosensitizers, the widening of the scope of applications, leveraging of the offerings of nanotechnology for greater efficacy, selectivity for the disease over host tissue and cells, the advent of combination therapies with other similarly minimally invasive therapeutic technologies, the use of stimulus-responsive delivery and disease targeting, and greater penetration depth of the activation energy. Brought together, all these milestones have contributed to the significant enhancement of what is still arguably a novel technology. Yet the major applications of photodynamic therapy still remain firmly located in neoplasms, from where most of the new innovations appear to launch to other areas, such as microbial, fungal, viral, acne, wet age-related macular degeneration, atherosclerosis, psoriasis, environmental sanitization, pest control, and dermatology. Three main value propositions of combinations of photodynamic therapy include the synergistic and additive enhancement of efficacy, the relatively low emergence of resistance and its rapid development as a targeted and high-precision therapy. Combinations with established methods such as chemotherapy and radiotherapy and demonstrated applications in mop-up surgery promise to enhance these top three clinical tools. From published in vitro and preclinical studies, clinical trials and applications, and postclinical case studies, seven combinations with photodynamic therapy have become prominent research interests because they are potentially easily applied, showing enhanced efficacy, and are rapidly translating to the clinic. These include combinations with chemotherapy, photothermal therapy, magnetic hyperthermia, cold plasma therapy, sonodynamic therapy, immunotherapy, and radiotherapy. Photochemical internalization is a critical mechanism for some combinations.},
}
@article {pmid37445820,
year = {2023},
author = {Weinberger, Y and Budnik, I and Nisgav, Y and Palevski, D and Ben-David, G and Fernández, JA and Margalit, SN and Levy-Mendelovich, S and Kenet, G and Weinberger, D and Griffin, JH and Livnat, T},
title = {3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina.},
journal = {International journal of molecular sciences},
volume = {24},
number = {13},
pages = {},
pmid = {37445820},
issn = {1422-0067},
support = {R01 HL142975/HL/NHLBI NIH HHS/United States ; },
mesh = {Mice ; Animals ; *Protein C/pharmacology/therapeutic use ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Vascular Endothelial Growth Factor A ; Retina/metabolism ; *Choroidal Neovascularization/pathology ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.},
}
@article {pmid37443812,
year = {2023},
author = {Tossetta, G and Piani, F and Borghi, C and Marzioni, D},
title = {Role of CD93 in Health and Disease.},
journal = {Cells},
volume = {12},
number = {13},
pages = {},
pmid = {37443812},
issn = {2073-4409},
mesh = {Humans ; *Endothelial Cells ; *Inflammation ; Monocytes ; Neovascularization, Pathologic ; },
abstract = {CD93 (also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp), is a transmembrane glycoprotein encoded by a gene located on 20p11.21 and composed of 652 amino acids. CD93 can be present in two forms: soluble (sCD93) and membrane-bound (CD93). CD93 is mainly expressed on endothelial cells, where it plays a key role in promoting angiogenesis both in physiology and disease, such as age-related macular degeneration and tumor angiogenesis. In fact, CD93 is highly expressed in tumor-associated vessels and its presence correlates with a poor prognosis, poor immunotherapy response, immune cell infiltration and high tumor, node and metastasis (TNM) stage in many cancer types. CD93 is also expressed in hematopoietic stem cells, cytotrophoblast cells, platelets and many immune cells, i.e., monocytes, neutrophils, B cells and natural killer (NK) cells. Accordingly, CD93 is involved in modulating important inflammatory-associated diseases including systemic sclerosis and neuroinflammation. Finally, CD93 plays a role in cardiovascular disease development and progression. In this article, we reviewed the current literature regarding the role of CD93 in modulating angiogenesis, inflammation and tumor growth in order to understand where this glycoprotein could be a potential therapeutic target and could modify the outcome of the abovementioned pathologies.},
}
@article {pmid37443742,
year = {2023},
author = {Khan, AH and Chowers, I and Lotery, AJ},
title = {Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment.},
journal = {Cells},
volume = {12},
number = {13},
pages = {},
pmid = {37443742},
issn = {2073-4409},
mesh = {Humans ; *Immunosenescence ; Endothelial Cells/metabolism ; Retina/metabolism ; *Macular Degeneration/metabolism ; Inflammation/pathology ; },
abstract = {Landmark genetic studies have revealed the effect of complement biology and its regulation on the pathogenesis of age-related macular degeneration (AMD). Limited phase 3 clinical trial data showing a benefit of complement inhibition in AMD raises the prospect of more complex mediators at play. Substantial evidence supports the role of para-inflammation in maintaining homeostasis in the retina and choroid. With increasing age, a decline in immune system regulation, known as immunosenescence, has been shown to alter the equilibrium maintained by para-inflammation. The altered equilibrium results in chronic, sterile inflammation with aging, termed 'inflammaging', including in the retina and choroid. The chronic inflammatory state in AMD is complex, with contributions from cells of the innate and adaptive branches of the immune system, sometimes with overlapping features, and the interaction of their secretory products with retinal cells such as microglia and retinal pigment epithelium (RPE), extracellular matrix and choroidal vascular endothelial cells. In this review, the chronic inflammatory state in AMD will be explored by immune cell type, with a discussion of factors that will need to be overcome in the development of curative therapies.},
}
@article {pmid37443724,
year = {2023},
author = {Ahluwalia, K and Martinez-Camarillo, JC and Thomas, BB and Naik, A and Gonzalez-Calle, A and Pollalis, D and Lebkowski, J and Lee, SY and Mitra, D and Louie, SG and Humayun, MS},
title = {Polarized RPE Secretome Preserves Photoreceptors in Retinal Dystrophic RCS Rats.},
journal = {Cells},
volume = {12},
number = {13},
pages = {},
pmid = {37443724},
issn = {2073-4409},
support = {P30 EY029220/EY/NEI NIH HHS/United States ; P30EY029220/EY/NEI NIH HHS/United States ; },
mesh = {Rats ; Humans ; Animals ; *Retinal Pigment Epithelium/metabolism ; *Retinal Degeneration/metabolism ; Secretome ; Retina/metabolism ; Photoreceptor Cells/metabolism ; },
abstract = {Retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa, lack effective therapies. Conventional monotherapeutic approaches fail to target the multiple affected pathways in retinal degeneration. However, the retinal pigment epithelium (RPE) secretes several neurotrophic factors addressing diverse cellular pathways, potentially preserving photoreceptors. This study explored human embryonic stem cell-derived, polarized RPE soluble factors (PRPE-SF) as a combination treatment for retinal degeneration. PRPE-SF promoted retinal progenitor cell survival, reduced oxidative stress in ARPE-19 cells, and demonstrated critical antioxidant and anti-inflammatory effects for preventing retinal degeneration in the Royal College of Surgeons (RCS) rat model. Importantly, PRPE-SF treatment preserved retinal structure and scotopic b-wave amplitudes, suggesting therapeutic potential for delaying retinal degeneration. PRPE-SF is uniquely produced using biomimetic membranes for RPE polarization and maturation, promoting a protective RPE secretome phenotype. Additionally, PRPE-SF is produced without animal serum to avoid immunogenicity in future clinical development. Lastly, PRPE-SF is a combination of neurotrophic factors, potentially ameliorating multiple dysfunctions in retinal degenerations. In conclusion, PRPE-SF offers a promising therapeutic candidate for retinal degenerative diseases, advancing the development of effective therapeutic strategies for these debilitating conditions.},
}
@article {pmid37443679,
year = {2023},
author = {Mujat, M and Akula, JD and Fulton, AB and Ferguson, RD and Iftimia, N},
title = {Non-Rigid Registration for High-Resolution Retinal Imaging.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {13},
pages = {},
pmid = {37443679},
issn = {2075-4418},
support = {P50 HD105351/HD/NICHD NIH HHS/United States ; R44 EY030812/EY/NEI NIH HHS/United States ; R01 EY010597/EY/NEI NIH HHS/United States ; R44EY018509/EY/NEI NIH HHS/United States ; R44 EY018509/EY/NEI NIH HHS/United States ; R01EY010597/EY/NEI NIH HHS/United States ; },
abstract = {Adaptive optics provides improved resolution in ophthalmic imaging when retinal microstructures need to be identified, counted, and mapped. In general, multiple images are averaged to improve the signal-to-noise ratio or analyzed for temporal dynamics. Image registration by cross-correlation is straightforward for small patches; however, larger images require more sophisticated registration techniques. Strip-based registration has been used successfully for photoreceptor mosaic alignment in small patches; however, if the deformations along strips are not simple displacements, averaging can degrade the final image. We have applied a non-rigid registration technique that improves the quality of processed images for mapping cones over large image patches. In this approach, correction of local deformations compensates for local image stretching, compressing, bending, and twisting due to a number of causes. The main result of this procedure is improved definition of retinal microstructures that can be better identified and segmented. Derived metrics such as cone density, wall-to-lumen ratio, and quantification of structural modification of blood vessel walls have diagnostic value in many retinal diseases, including diabetic retinopathy and age-related macular degeneration, and their improved evaluations may facilitate early diagnostics of retinal diseases.},
}
@article {pmid37440059,
year = {2023},
author = {Hollingsworth, TJ and Wang, X and Simpson, RN and White, WA and Williams, RW and Jablonski, MM},
title = {Current Advancements in Mouse Models of Retinal Disease.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {371-376},
pmid = {37440059},
issn = {0065-2598},
mesh = {Mice ; Animals ; Humans ; *Retinal Degeneration/therapy ; *Retinitis Pigmentosa/genetics/therapy ; *Macular Degeneration/genetics/therapy ; Disease Models, Animal ; Vision, Ocular ; },
abstract = {The field of retinal degenerative (RDs) disease study has been in a state of exponential growth from discovering the underlying genetic components of such diseases as age-related macular degeneration (AMD) and retinitis pigmentosa (RP) to the first gene therapy developed and approved for human Leber congenital amaurosis. However, a source for high-fidelity animal models of these complex, multifactorial, and/or polygenic diseases is a need that has yet to be fulfilled. While models for AMD and RP do exist, they often require aging the animals for a year or more, feeding special diets, or introduction of external modulators such as exposure to cigarette smoke. Currently, work is being done to uncover high-fidelity naturally occurring models of these retinal diseases with the hope and intent of providing the vision community the tools it needs to better understand, treat, and, one day, cure the patients suffering from these devastating afflictions.},
}
@article {pmid37440057,
year = {2023},
author = {Garland, D and Harnly, J and Ayyagari, R},
title = {Mouse Choroid Proteome Revisited: Focus on Aging.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {359-363},
pmid = {37440057},
issn = {0065-2598},
mesh = {Animals ; Mice ; *Bruch Membrane/chemistry ; Proteome/analysis ; Choroid ; *Macular Degeneration/metabolism ; Aging/genetics ; },
abstract = {Age is a major risk factor for age-related macular degeneration (AMD), and age has a role in the disease phenotypes of heritable macular dystrophies. The proteomes of C57Bl6/J mouse choroids at 2 ages were analyzed to identify biochemical processes affected by aging. Proteins of interest were identified as those contributing most to the variance in principal component analysis and those showing the largest significant differences between ages. These proteins implicated altered ECM composition, immune system function, and lipid metabolism.},
}
@article {pmid37440051,
year = {2023},
author = {Pan, HY and Valapala, M},
title = {Role of TFEB in Diseases Associated with Lysosomal Dysfunction.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {319-325},
pmid = {37440051},
issn = {0065-2598},
mesh = {*Gene Expression Regulation ; *Lysosomes/metabolism ; Transcription Factors/metabolism ; Autophagy/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/metabolism/pharmacology ; },
abstract = {Transcription factor EB (TFEB) plays a very important role in the maintenance of cellular homeostasis. TFEB is a transcription factor that regulates the expression of several genes in the Coordinated Lysosomal Expression and Regulation (CLEAR) network. The CLEAR network genes are known to regulate many processes associated with the autophagy pathway and lysosome biogenesis. Lysosomes, which are degradative organelles in the cell, are associated with several cellular mechanisms, such as autophagy and phagocytosis. Recent studies have shown that TFEB dysregulation and lysosomal dysfunction are associated with several degenerative diseases. Thus, enhancing TFEB activity and accompanied induction of lysosomal function and autophagy can have tremendous therapeutic potential for the treatment of several degenerative diseases including age-related macular degeneration (AMD). In this chapter, we briefly illustrate the expression and regulation of TFEB in response to several cellular stressors and discuss the effects of TFEB overexpression to induce cellular clearance functions.},
}
@article {pmid37440043,
year = {2023},
author = {Hayes, MH and Woodard, DR and Hulleman, JD},
title = {Ocular Amyloid, Condensates, and Aggregates - Higher-Order Protein Assemblies Participate in Both Retinal Degeneration and Function.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {263-267},
pmid = {37440043},
issn = {0065-2598},
support = {P30 EY030413/EY/NEI NIH HHS/United States ; },
mesh = {*Retinal Degeneration/genetics/pathology ; Amyloidogenic Proteins ; *Macular Degeneration/genetics/pathology ; Optic Disk Drusen/congenital ; Protein Aggregates ; Humans ; Mice ; Retina/pathology ; Animals ; },
abstract = {The formation of higher-order protein assemblies (commonly called protein aggregates) has long been associated with disease states, particularly in neurodegenerative disorders. Within the eye, protein aggregation has also been implicated in various retinal degenerative diseases ranging from retinitis pigmentosa (RP) to Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy (ML/DHRD) to age-related macular degeneration (AMD). Yet, many essential cellular processes including transcription, translation, and the formation of non-membrane bound organelles require the formation of functional, non-pathologic protein aggregates to maintain cellular homeostasis. Thus, functional protein aggregates, also called condensates, likely play essential roles in maintaining normal retina function. However, currently, there is a critical gap in our knowledge: What proteins form higher-order assemblies under normal conditions within the retina and what function do these structures serve? Herein, we present data suggesting that protein aggregation is identifiable in multiple retinal layers of normal, healthy murine retina, and briefly discuss the potential contributions of aggregated proteins to normal retinal function, with a focus on the photoreceptor inner and outer segment.},
}
@article {pmid37440042,
year = {2023},
author = {Gorusupudi, A and Nwagbo, U and Bernstein, PS},
title = {Role of VLC-PUFAs in Retinal and Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {257-261},
pmid = {37440042},
issn = {0065-2598},
mesh = {Humans ; *Membrane Proteins ; Retina ; *Macular Degeneration ; Fatty Acids ; Fatty Acids, Unsaturated/chemistry ; Eye Proteins ; },
abstract = {Very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are a special class of fatty acids that are present in the retina and a few other human tissues. They cannot be synthesized de novo and are rarely present in dietary sources. Structurally, these lipids are composed of a proximal end with a typical saturated fatty acid character and a distal end more characteristic of common PUFAs. They have not been studied in detail until recently due to their low abundance in these tissues and technical difficulties in assaying these lipids by conventional chromatography. This unique class of lipids has chain lengths greater than 24 carbons, with the longest typically 38 carbons long. There is increasing interest in understanding their roles in the maintenance of retinal membrane integrity and the prevention of macular degeneration and inherited retinal diseases.},
}
@article {pmid37440035,
year = {2023},
author = {Choudhary, M and Malek, G},
title = {CD68: Potential Contributor to Inflammation and RPE Cell Dystrophy.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {207-213},
pmid = {37440035},
issn = {0065-2598},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; Humans ; Aged ; Retinal Pigment Epithelium/pathology ; Retina/pathology ; *Macular Degeneration/pathology ; *Retinal Degeneration/pathology ; Inflammation/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly in developed countries. It is a complex, multifactorial, progressive disease with diverse molecular pathways, including inflammation, regulating its pathogenesis. The myeloid marker CD68 is a protein highly expressed in circulating and tissue macrophages. Recent observations of immune markers in human AMD tissues have varied with some finding ectopic RPE cells in advanced AMD and others noting negligible numbers of CD68-positive cells. Additionally, animal models of retinal degeneration have shown upregulation of CD68, in a protective population of retinal microglia. Herein, we review the potential role of CD68 in regulating RPE health and inflammation in the sub-retinal space and discuss observations on its localization in a mouse model that presents with AMD-like features.},
}
@article {pmid37440029,
year = {2023},
author = {Grunin, M and Palmer, E and de Jong, S and Jin, B and Rinker, D and Moth, C and Capra, JA and Haines, JL and Bush, WS and den Hollander, AI},
title = {Integrating Computational Approaches to Predict the Effect of Genetic Variants on Protein Stability in Retinal Degenerative Disease.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {157-163},
pmid = {37440029},
issn = {0065-2598},
mesh = {Humans ; *Retinal Degeneration/genetics ; Retina ; *Macular Degeneration/genetics ; Mutation ; Proteins/chemistry ; Protein Stability ; },
abstract = {Protein function can be impacted by changes in protein structure stability, but determining which change has impact is complex. Stability can be affected by a large change in the tertiary (3D) structure of the protein or due to free-energy changes caused by single amino acid substitutions. Changes in the DNA sequence can have minor or major impact on protein stability, which can lead to disease. Inherited retinal degenerations are generally caused by single mutations which are mostly located in protein-coding regions, while age-related macular degeneration (AMD) is a complex disorder that can be influenced by some genetic variants impacting proteins involved in the disease, although not all AMD risk variants lead to amino acid changes. Here, we review ways that proteins may be affected, the identification and understanding of these changes, and how to identify causal changes that can be targeted to develop treatments to alleviate retinal degenerative disease.},
}
@article {pmid37440020,
year = {2023},
author = {Caruso, SM and Tsai, YT and da Costa, BL and Kolesnikova, M and Jenny, LA and Tsang, SH and Quinn, PMJ},
title = {Prime Editing Strategy to Install the PRPH2 c.828+1G&gt;A Mutation.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {97-102},
pmid = {37440020},
issn = {0065-2598},
support = {T32 EY013933/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Peripherins/genetics ; *Retinal Degeneration/genetics/therapy/pathology ; *Retinitis Pigmentosa/genetics/pathology ; *Macular Degeneration/genetics/pathology ; Mutation ; Atrophy ; },
abstract = {Mutations in peripherin 2 (PRPH2) are associated with a spectrum of inherited retinal diseases (IRDs) including retinitis pigmentosa (RP) and macular degeneration. As PRPH2 is localized to cone and rod outer segments, mutations in PRPH2 lead the disorganization or absence of photoreceptor outer segments. Here, we report on a patient with PRPH2-linked RP who exhibited widespread RPE atrophy with a central area of macular atrophy sparing the fovea. In future studies, we plan to model the pathobiology of PRPH2-based RP using induced pluripotent stem cell (iPSC)-derived retinal organoids. To effectively model rare mutations using iPSC-derived retinal organoids, we first require a strategy that can install the desired mutation in healthy wild-type iPSC, which can efficiently generate well-laminated retinal organoids. In this study, we developed an efficient prime editing strategy for the installation of the pathogenic PRPH2 c.828+1 G>A splice-site mutation underlying our patient's disease.},
}
@article {pmid37440019,
year = {2023},
author = {Cioanca, AV and Natoli, R and Wooff, Y},
title = {Proteomics of Retinal Extracellular Vesicles: A Review into an Unexplored Mechanism in Retinal Health and AMD Pathogenesis.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {87-94},
pmid = {37440019},
issn = {0065-2598},
mesh = {Humans ; Proteomics ; Retina/pathology ; *Extracellular Vesicles/metabolism ; Eye Proteins/metabolism ; *Retinal Degeneration/pathology ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Extracellular vesicles (EV) are nanosized delivery vehicles that participate in cell-to-cell communication through the selective transfer of molecular materials including RNA, DNA, lipids, and proteins. In the retina, the role of EV proteins is largely unclear, in part due to the lack of studies and the depth of proteomic analyses of EV cargo. This review summarizes the existing knowledge on retinal EV proteins and provides a comparative reanalysis of existing retinal EV proteomic datasets. Collective findings highlight that in homeostasis, the protein components of neural retinal and RPE-derived EV largely reflect the function of the host cells, while in disease RPE-EV protein composition becomes altered, favoring inflammatory modulation and potentially contributing to drusen formation. While these studies shed light on the potential roles of EV proteins in the neural retina and RPE, it is clear that comprehensive proteomic and molecular studies are required, in particular using in vivo models of retinal degenerations.},
}
@article {pmid37440017,
year = {2023},
author = {Francisco, SG and Rowan, S},
title = {Repurposing Drugs for Treatment of Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {73-77},
pmid = {37440017},
issn = {0065-2598},
mesh = {Humans ; Drug Repositioning ; *Macular Degeneration/drug therapy ; Levodopa ; *Metformin/therapeutic use ; },
abstract = {The need for new drugs to treat dry forms of age-related macular degeneration remains high. A promising approach is repurposing of FDA-approved medications to treat AMD. Databases containing medical and drug records allow for retroactive identification of drugs whose use correlates with reduced AMD diagnosis. This short review summarizes progress in several classes of drugs considered for repurposing: GPR-143 agonists (L-DOPA), anti-diabetic drugs (metformin, acarbose, empagliflozin, fenofibrate), mitochondrial activators (PU-91), and serotonin pathway drugs (fluoxetine, flibanserin, xaliproden, buspirone). The promises and caveats of repurposing are discussed herein.},
}
@article {pmid37440016,
year = {2023},
author = {Rohrer, B and Parsons, N and Annamalai, B and Nicholson, C and Obert, E and Jones, B and Dick, AD},
title = {Elastin Layer in Bruch's Membrane as a Target for Immunization or Tolerization to Modulate Pathology in the Mouse Model of Smoke-Induced Ocular Injury.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {67-71},
pmid = {37440016},
issn = {0065-2598},
mesh = {Mice ; Animals ; *Bruch Membrane/pathology ; Elastin/metabolism ; Immunization ; *Macular Degeneration/metabolism ; Immunoglobulin M ; Immunoglobulin G ; },
abstract = {Age-related macular degeneration (AMD) is associated with an overactive complement system and an increase in circulating antibodies. Our search for potential neoantigens that can trigger complement activation in disease has led us to investigate elastin. A loss of the elastin layer (EL) of Bruch's membrane (BrM) has been reported in aging and AMD together with an increase of serum elastin-derived peptides and α-elastin antibodies. In the mouse model of cigarette smoke exposure (CSE), damage in BrM, loss of the EL, and vision loss are dependent on complement activation. We have examined the hypothesis that CSE generates immunogenic elastin neoepitopes that trigger an increase in α-elastin IgG and IgM antibodies, which can then bind to the neoepitopes in the target cells or membranes, triggering complement activation. Specifically, we showed that immunization with elastin peptide oxidatively modified by cigarette smoke (ox-elastin) exacerbated ocular pathology and vision loss in CSE mice. In contrast, mice receiving peptide immunotherapy (PIT) with ox-elastin did not lose vision over the smoking period and exhibited a more preserved BrM. Immunization and PIT correlated with humoral immunity and complement activation and IgG/IgM deposition in the RPE/BrM/choroid. Finally, PIT modulated immune markers IFNγ and IL-4. The data further support the hypothesis that complement activation, triggered by immune complex formation in target tissues, plays a role in ocular damage in the CSE model. As PIT with ox-elastin peptides reduces damage, we discuss the possibility that AMD progression might be preventable.},
}
@article {pmid37440015,
year = {2023},
author = {Ratnapriya, R},
title = {The Role of Gene Expression Regulation on Genetic Risk of Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {61-66},
pmid = {37440015},
issn = {0065-2598},
mesh = {Humans ; Aged ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Gene Expression Regulation ; Quantitative Trait Loci ; *Macular Degeneration/genetics/metabolism ; Risk Factors ; Polymorphism, Single Nucleotide ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in the elderly. It is a complex multifactorial disease that is caused by the cumulative impact of genetic predisposition, environmental stress, and advanced aging. Knowledge of genetic risk factors underlying AMD susceptibility has advanced rapidly in the past decade that can be largely credited to genome-wide association studies (GWAS) and next-generation sequencing (NGS) efforts. GWAS have identified 34 genetic risk loci for AMD; the majority of which are in the noncoding genome. Several lines of evidence suggest that a complex trait-associated variant is likely to regulate the gene expression (acting as expression quantitative trait loci (eQTLs)), and there is a significant enrichment of GWAS-associated variants within eQTLs. In the last two years, eQTL studies in AMD-relevant tissues have provided functional interpretation of several AMD-GWAS loci. This review highlights the knowledge gained to date and discusses future directions to bridge the gap between genetic predisposition and biological mechanisms to reap the full benefits of GWAS findings.},
}
@article {pmid37440014,
year = {2023},
author = {Peters, F and Grimm, C},
title = {Regulation of ABCA1 by miR-33 and miR-34a in the Aging Eye.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {55-59},
pmid = {37440014},
issn = {0065-2598},
mesh = {Humans ; Cholesterol/metabolism ; Genome-Wide Association Study ; *MicroRNAs/genetics/metabolism ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/genetics/metabolism ; Aging/genetics ; ATP Binding Cassette Transporter 1/genetics/metabolism ; },
abstract = {Many age-related diseases, including age-related macular degeneration (AMD), go along with local lipid accumulation and dysregulated lipid metabolism. Several genes involved in lipid metabolism, including ATP-binding cassette transporter A1 (ABCA1), were associated with AMD through genome-wide association studies. Recent studies have shown that loss of ABCA1 in the retinal pigment epithelium (RPE) leads to lipid accumulation and RPE atrophy, a hallmark of AMD, and that antagonizing ABCA1-targeting microRNAs (miRNAs) attenuated pathological changes to the RPE or to macrophages. Here, we focus on two lipid metabolism-modulating miRNAs, miR-33 and miR-34a, which show increased expression in aging RPE cells, and on their potential to regulate ABCA1 levels, cholesterol efflux, and lipid accumulation in AMD pathogenesis.},
}
@article {pmid37440013,
year = {2023},
author = {Mowat, FM},
title = {Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1Alpha (PGC-1α): A Transcriptional Regulator at the Interface of Aging and Age-Related Macular Degeneration?.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {49-53},
pmid = {37440013},
issn = {0065-2598},
mesh = {Humans ; Mice ; Animals ; *PPAR gamma ; Mitochondria/metabolism ; Aging/genetics ; Oxidative Stress ; *Macular Degeneration/pathology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics ; },
abstract = {Human age-related macular degeneration (AMD) is a prevalent age-related disease which causes retinal dysfunction and disability. Genetic and cell culture studies from AMD patients have implicated impaired activity of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α). PGC-1α is a transcriptional co-regulator that acts to control a plethora of metabolic processes relevant to AMD pathophysiology including gluconeogenesis, oxidative phosphorylation, and response to oxidative injury. Perturbation of PGC-1α activity in mice causes AMD-like RPE and retinal pathology. There is potential for therapeutic modulation of the PGC-1α pathway in AMD treatment.},
}
@article {pmid37440012,
year = {2023},
author = {Tung, D and McKay, BS},
title = {Decoding Race and Age-Related Macular Degeneration: GPR 143 Activity Is the Key.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {43-47},
pmid = {37440012},
issn = {0065-2598},
mesh = {Humans ; *Levodopa ; *Macular Degeneration/genetics/metabolism ; Retina/metabolism ; Retinal Pigment Epithelium/metabolism ; Choroid ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the developed world. Caucasians are eightfold more likely to develop AMD than any other race, indicating a racial bias in AMD incidence which is unexplained. We hypothesize that pigmentation of the retinal pigment epithelium (RPE) and choroid protects from AMD and underlies this peculiar racial bias. We investigated GPR143, a receptor in the pigmentation pathway, which is activated by a melanin synthesis by-product, l-dopa. In this model, greater pigmentation leads to greater l-dopa production and, in turn, greater GPR143 signaling. GPR143 activity upregulates PEDF and downregulates both VEGF and exosomes; all of which reduce the angiogenic potential in the retina. Moreover, we demonstrate that GPR143 signaling enhances the digestion of shed photoreceptor outer segments. Together, our data suggests a central role for GPR143 signaling in RPE-photoreceptor interaction which is critical to healthy vision.},
}
@article {pmid37440011,
year = {2023},
author = {Kotnala, A and Anderson, DMG and Messinger, JD and Curcio, CA and Schey, KL},
title = {Untargeted Lipidomic Profiling of Aged Human Retina With and Without Age-Related Macular Degeneration (AMD).},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {37-42},
pmid = {37440011},
issn = {0065-2598},
mesh = {Humans ; Aged ; *Tandem Mass Spectrometry ; Chromatography, Liquid/methods ; Lipidomics ; Retina ; *Macular Degeneration ; Lipids/chemistry ; },
abstract = {The molecular characterization of extracellular deposits is crucial to understanding the clinical progression of AMD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis is a powerful analytical discovery tool capable of identifying lipids in an untargeted manner. NanoLC-MS/MS is an analytical tool capable of identifying lipids with high sensitivity and minimum sample usage. Hence, the purpose of this study was to compare retina lipid identification from RPE-choroid samples using high flow LC-MS/MS and nanoLC-MS/MS. Manually dissected paraformaldehyde-fixed human donor tissues sections were used for LC-MS/MS and nanoLC-MS/MS analysis. Lipids were extracted with MeOH/MTBE/CHCl3 (MMC) and were analyzed by LC-MS/MS and nanoLC-MS/MS using negative and positive ionization modes. Untargeted lipidomics using LC-MS/MS identified 215 lipids from 4 lipid classes and 15 subclasses. We observed a 78% increase in lipid identifications using nanoLC-MS/MS with lipid numbers totaling 384. The nanoLC-MS/MS method is expected to provide extensive lipid identifications from small retina samples, e.g., from drusen and drusenoid deposits in aged and AMD eyes, and could help elucidate how lipids are involved in extracellular deposit formation in AMD.},
}
@article {pmid37440010,
year = {2023},
author = {Gogna, N and Hyde, LF and Collin, GB and Stone, L and Naggert, JK and Nishina, PM},
title = {Current Views on Chr10q26 Contribution to Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {27-36},
pmid = {37440010},
issn = {0065-2598},
support = {R01 EY035397/EY/NEI NIH HHS/United States ; U54 OD020351/OD/NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Proteins/genetics ; Serine Endopeptidases/genetics ; Genome-Wide Association Study ; High-Temperature Requirement A Serine Peptidase 1/genetics ; *Macular Degeneration/genetics ; Linkage Disequilibrium ; Polymorphism, Single Nucleotide ; Complement Factor H/genetics ; Genotype ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in the global aging population. Familial aggregation and genome-wide association (GWA) studies have identified gene variants associated with AMD, implying a strong genetic contribution to AMD development. Two loci, on human Chr 1q31 and 10q26, respectively, represent the most influential of all genetic factors. While the role of CFH at Chr 1q31 is well established, uncertainty remains about the genes ARMS2 and HTRA1, at the Chr 10q26 locus. Since both genes are in strong linkage disequilibrium, assigning individual gene effects is difficult. In this chapter, we review current literature about ARMS2 and HTRA1 and their relevance to AMD risk. Future studies will be necessary to unravel the mechanisms by which they contribute to AMD.},
}
@article {pmid37440009,
year = {2023},
author = {Martins, B and Fernandes, R},
title = {Disturbed Matrix Metalloproteinases Activity in Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {21-26},
pmid = {37440009},
issn = {0065-2598},
mesh = {Humans ; *Macular Degeneration/genetics/metabolism ; Bruch Membrane/metabolism ; Choroid ; Retinal Pigment Epithelium/metabolism ; Matrix Metalloproteinases/genetics/metabolism ; },
abstract = {Matrix metalloproteinases (MMPs) are a tightly regulated family of proteolytic enzymes that break down extracellular matrix (ECM) and basement membrane components. Because it is associated with development, morphogenesis, tissue remodeling, and repair, ECM remodeling is an important mechanism. MMPs are thought to act as a double-edged sword, as they contribute to maintaining photoreceptors/retinal pigment epithelium (RPE)/Bruch's membrane (BM)/choroid complex homeostasis and also contribute to the onset and progression of age-related macular degeneration (AMD). Polymorphisms and/or altered expression in MMPs and their tissue inhibitors (TIMPs) are associated with age-related macular degeneration (AMD). Here, we review the evidence for MMPs' role in the onset and progression of AMD via addressing their regulation and TIMPs' significant regulatory functions.},
}
@article {pmid37440008,
year = {2023},
author = {Arunkumar, R and Bernstein, PS},
title = {Macular Pigment Carotenoids and Bisretinoid A2E.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {15-20},
pmid = {37440008},
issn = {0065-2598},
mesh = {Humans ; Lutein ; *Macula Lutea ; *Macular Degeneration/genetics/metabolism ; *Macular Pigment/metabolism ; Retina/metabolism ; Retinoids/pharmacology ; },
abstract = {Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) are the three macular pigments (MP) carotenoids that uniquely accumulate in the macula lutea region of the human retina. L and Z are obtained by humans through dietary intake. The third MP, MZ, is rarely present in diet, and its abundance in the human fovea is due to the metabolic conversion of dietary L by the retinal pigment epithelium's RPE65 enzyme. The major functions of MP in ocular health are to filter high-intensity, phototoxic blue light and to act as effective antioxidants for scavenging free radicals. The pyridinium bisretinoid, N-retinylidene-N-retinylethanolamine (A2E), contributes to drusen formation in dry age-related macular degeneration (AMD) and to the autofluorescent flecks in autosomal recessive Stargardt disease (STGD1). Retinal carotenoids attenuate A2E formation and can directly and indirectly alleviate A2E-mediated oxidative damage. In this chapter, we review these more recently recognized interconnections between MP carotenoids and A2E bisretinoids.},
}
@article {pmid37440007,
year = {2023},
author = {Armento, A and Merle, DA and Ueffing, M},
title = {The Noncanonical Role of Complement Factor H in Retinal Pigment Epithelium (RPE) Cells and Implications for Age-Related Macular Degeneration (AMD).},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {9-13},
pmid = {37440007},
issn = {0065-2598},
mesh = {Humans ; *Complement Factor H/genetics/metabolism ; Retinal Pigment Epithelium ; *Macular Degeneration/genetics/metabolism ; Complement Activation/genetics ; Genetic Predisposition to Disease ; },
abstract = {Age-related macular degeneration (AMD) is a complex degenerative disease of the retina. Dysfunction of the retinal pigment epithelium (RPE) occurs in early stages of AMD, and progressive RPE atrophy leads to photoreceptor death and visual impairments that ultimately manifest as geographic atrophy (GA), one of the late-stage forms of AMD. AMD is caused by a combination of risk factors including aging, lifestyle choices, and genetic predisposition. A gene variant in the complement factor H gene (CFH) that leads to the Y402H polymorphism in the factor H protein (FH) confers the second highest risk for the development and progression of AMD. FH is a major negative regulator of the alternative pathway of the complement system, and the FH Y402H variant leads to increased complement activation, which is detectable in AMD patients. For this reason, various therapeutic approaches targeting the complement system have been developed, however, so far with very limited or no efficacy. Interestingly, recent studies suggest roles for FH beyond complement regulation. Here, we will discuss the noncanonical functions of FH in RPE cells and highlight the potential implications of those functions for future therapeutic approaches.},
}
@article {pmid37440006,
year = {2023},
author = {Anderson, DMG and Kotnala, A and Messinger, JD and Patterson, NH and Spraggins, JM and Curcio, CA and Caprioli, RM and Schey, KL},
title = {High-Resolution Imaging Mass Spectrometry of Human Donor Eye: Photoreceptors Cells and Basal Laminar Deposit of Age-Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1415},
number = {},
pages = {3-7},
pmid = {37440006},
issn = {0065-2598},
mesh = {Humans ; Aged ; *Macular Degeneration/diagnostic imaging/pathology ; Retina/pathology ; Basement Membrane ; Photoreceptor Cells/pathology ; Mass Spectrometry ; },
abstract = {Pathologies of the retina are clinically visualized in vivo with OCT and ex vivo with immunohistochemistry. Although both techniques provide valuable information on prognosis and disease state, a comprehensive method for fully elucidating molecular constituents present in locations of interest is desirable. The purpose of this work was to use multimodal imaging technologies to localize the vast number of molecular species observed with matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) in aged and diseased retinal tissues. Herein, MALDI IMS was utilized to observe molecular species that reside in photoreceptor cells and also a basal laminar deposit from two human donor eyes. The molecular species observed to accumulate in these discrete regions can be further identified and studied to attempt to gain a greater understanding of biological processes occurring in debilitating eye diseases such as age-related macular degeneration (AMD).},
}
@article {pmid37439028,
year = {2024},
author = {Shi, H and Guo, N and Zhao, Z and He, X and Li, J and Duan, J},
title = {Global prevalence of myopic macular degeneration in general population and patients with high myopia: A systematic review and meta-analysis.},
journal = {European journal of ophthalmology},
volume = {34},
number = {3},
pages = {631-640},
doi = {10.1177/11206721231185816},
pmid = {37439028},
issn = {1724-6016},
mesh = {Humans ; Prevalence ; *Myopia, Degenerative/epidemiology/ethnology ; *Global Health ; *Macular Degeneration/epidemiology ; Risk Factors ; },
abstract = {The prevalence of myopic macular degeneration (MMD) in the general population and patients with high myopia worldwide has not been fully investigated. Therefore, we screened all population-based studies that reported the prevalence of MMD, and pooled prevalence of MMD using a random-effect model. Subgroup analyses were performed to explore the differences in MMD prevalence in the general population and patients with high myopia according to ethnicity, region of residence (urban/rural), and grading system. Finally, 16 studies were included in this meta-analysis. Results obtained from 2,963 patients from seven countries on four continents indicated that the pooled prevalence of MMD in patients with high myopia was 49.0% (95% CI: 31.5%-66.7%). Results obtained from 71,052 participants from 10 countries on four continents suggested that the pooled prevalence of MMD in the general population was 1.7% (95% CI: 1.1%-2.6%). In the general population, living in urban areas and East Asians were associated with a high prevalence of MMD. Among patients with high myopia, only East Asians were at a higher risk of developing MMD. In conclusion, MMD was particularly prevalent in patients with high myopia. Compared with Europeans, East Asians (Chinese and Japanese) have a higher propensity of developing MMD, both in the general population and in patients with high myopia. It remains unclear whether the higher prevalence of MMD in patients with high myopia in East Asia is caused by differences in given age or given degree of myopia.Systematic review registration number: 202270014 (INPLASY.COM).},
}
@article {pmid37438681,
year = {2023},
author = {Park, JB and Kim, K and Kang, MS and Kim, ES and Yu, SY},
title = {Optical coherence tomography angiography biomarkers in a bi-monthly maintenance dosing aflibercept in patients with neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {314},
pmid = {37438681},
issn = {1471-2415},
support = {20306//Bayer/ ; },
mesh = {Humans ; *Tomography, Optical Coherence ; Prospective Studies ; Angiography ; Biomarkers ; *Macular Degeneration ; },
abstract = {PURPOSE: To evaluate the correlations between swept-source optical coherence tomography angiography (SS-OCTA) parameters and clinical outcomes in eyes with neovascular age-related macular degeneration (nAMD) administered a bimonthly intravitreal aflibercept regimen.<br><br>METHODS: This prospective, single-arm, interventional study enrolled 33 patients with treatment-na&#xef;ve nAMD. The eyes received three monthly aflibercept injections followed by five bi-monthly regimens (total 50 weeks). The structural parameters including central subfield thickness (CST) and 5&#xa0;mm pigment epithelial detachment (PED) volume and microvascular parameters including macular neovascularization (MNV) area, vessel density (VD), and vessel length density (VLD) were recorded every before and 1 week after treatment.<br><br>RESULTS: Patients who gained&#x2009;>&#x2009;5 letters of best-corrected visual acuity (BCVA) from the baseline showed greater decreases in VD and VLD during the loading phase. Patients without recurrent or persistent fluid during the maintenance phase showed greater decreases in CST and 5&#xa0;mm PED volume after the first injection. The decrease in mean VD during the loading phase was significantly correlated with the final BCVA (r = -0.820, p&#x2009;=&#x2009;0.004). Moreover, the decrease in mean VLD during the loading phase was significantly correlated with the improvement in the final BCVA (r = -0.726, p&#x2009;=&#x2009;0.017).<br><br>CONCLUSIONS: The decrease in mean VD during the loading phase was significantly negatively correlated with the final BCVA at the last visit. The decrease in mean VLD during the loading phase, mean CST during the loading phase, and the improvement in final BCVA showed significant correlations. Therefore, early changes in OCTA microvascular and OCT structural parameters could help predict clinical outcomes in nAMD.<br><br>TRIAL REGISTRATION: The trial was registered with the Clinical Research Information Service (CRIS), which joined the WHO International Clinical Trials Registry Platform (ICTRP) (Registration number: KCT0007375, Date of first trial registration: 10/06/2022).},
}
@article {pmid37437978,
year = {2023},
author = {Dabravolski, SA},
title = {Mitochondria-derived peptides in healthy ageing and therapy of age-related diseases.},
journal = {Advances in protein chemistry and structural biology},
volume = {136},
number = {},
pages = {197-215},
doi = {10.1016/bs.apcsb.2023.02.015},
pmid = {37437978},
issn = {1876-1631},
mesh = {Humans ; *Healthy Aging ; Mitochondria/genetics ; Peptides ; *Alzheimer Disease/genetics/therapy ; },
abstract = {Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by mitochondrial DNA and involved in various stress-protecting mechanisms. To date, eight mitochondrial-derived peptides have been identified: MOTS-c sequence is hidden in the 12 S rRNA gene (MT-RNR1), and the other 7 (humanin and small humanin-like peptides 1-6) are encoded by the 16 S rRNA (MT-RNR2) gene. While the anti-apoptotic, anti-inflammatory and cardioprotective activities of MDPs are well described, recent research suggests that MDPs are sensitive metabolic sensors, closely connected with mtDNA mutation-associated diseases and age-associated metabolic disorders. In this chapter, we focus on the recent progress in understanding the metabolo-protective properties of MDPs, their role in maintenance of the cellular and mitochondrial homeostasis associated with age-related diseases: Alzheimer's disease, cognitive decline, macular degeneration and cataracts. Also, we will discuss MDPs-based and MDPs-targeted interventions to treat age-related diseases and extend a healthy lifespan.},
}
@article {pmid37437833,
year = {2024},
author = {Großpötzl, M and Kloeckl, L and Guttmann, A and Kruger, M and Gran, J and Hoeflechner, L and Brandner, M and Gaugl, H and Ivastinovic, D and Lindner, M and Riedl, R and Wedrich, A and Lindner, E},
title = {Protective Effect of Amblyopia on Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {259},
number = {},
pages = {1-6},
doi = {10.1016/j.ajo.2023.07.006},
pmid = {37437833},
issn = {1879-1891},
mesh = {Humans ; *Amblyopia/diagnosis ; Visual Acuity ; Retrospective Studies ; Cross-Sectional Studies ; *Macular Degeneration/complications/diagnosis ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: Our aim was to evaluate whether patients with age-related macular degeneration (AMD) and cooccurrent amblyopia are more likely to have diseases diagnosed on both the ipsilateral and the contralateral side in a large Austrian database.<br><br>DESIGN: Retrospective cross-sectional study.<br><br>METHODS: Setting: Institutional practice.<br><br>PATIENT POPULATION: Medical records of all patients who visited the Department of Ophthalmology of the Medical University of Graz between December 1996 and June 2021 were searched for the co-occurrence of AMD and amblyopia.<br><br>MAIN OUTCOME MEASURES: Data from patients with AMD diagnosed on 1 eye side were used for further analysis. Spectral-domain optical coherence tomography images were analyzed to confirm the lateral asymmetry of AMD.<br><br>RESULTS: A total of 327,443 patients were screened for the co-occurrence of AMD and amblyopia. Of them, 8742 patients had AMD diagnosed on 1 eye side and 5051 patients had unilateral amblyopia. In total, 163 patients were found to have AMD diagnosed on 1 side and unilateral amblyopia in combination. Of these, 126 patients had AMD and amblyopia on contralateral sides and 37 had AMD and amblyopia on the ipsilateral side (P < .001).<br><br>CONCLUSIONS: Less amblyopic patients had AMD diagnosed on the amblyopic eye compared with the nonamblyopic eye. In cases of lateral asymmetry, the nonamblyopic eye is more likely to have the more advanced form of AMD.},
}
@article {pmid37437830,
year = {2023},
author = {Seddon, JM and De, D and Rosner, B},
title = {Family History of Age-Related Macular Degeneration and Genetics Predict Progression to Advanced Age-Related Macular Degeneration Adjusting for Macular Status, Demographic, and Lifestyle Factors.},
journal = {American journal of ophthalmology},
volume = {255},
number = {},
pages = {74-86},
pmid = {37437830},
issn = {1879-1891},
support = {R01 EY011309/EY/NEI NIH HHS/United States ; R01 EY012269/EY/NEI NIH HHS/United States ; R01 EY022445/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Longitudinal Studies ; Prospective Studies ; Disease Progression ; *Macular Degeneration/diagnosis/genetics ; Risk Factors ; Life Style ; Demography ; },
abstract = {PURPOSE: To determine if a family history of age-related macular degeneration (AMD) and genetic variants identify eyes at higher risk for progression to advanced AMD (AAMD), after controlling for baseline demographics, behavioral factors, and macular status.<br><br>DESIGN: Prospective, longitudinal cohort study.<br><br>METHODS: Eyes were classified using the Age-Related Eye Disease Study severity scale. Non-genetic and genetic predictors for progression to AAMD, geographic atrophy, and neovascular disease were evaluated. Cox proportional hazards models using the eye as the unit of analysis were used to calculate hazard ratios (HRs), accounting for correlated data. Discrimination between progressing and non-progressing eyes was assessed using C-statistics and net reclassification improvement (NRI).<br><br>RESULTS: Among 4910 eyes, 863 progressed to AAMD over 12 years. Baseline AMD severity scale and status of the fellow eye were important predictors; genes provided additional discrimination. A family history of AMD also independently predicted progression after accounting for genetic and other covariates: 1 family member versus none (HR 1.21 [95% confidence interval {CI}
1.02-1.43]; P&#xa0;=&#xa0;0.03); &#x2265;2 family members versus none (HR 1.55 [95% CI 1.26-1.90]; P < 0.001). A composite risk score calculated using &#x3b2; estimates of both non-genetic and significant genetic factors predicted progression to AAMD (HR 5.57; 90[th] vs 10[th] percentile; area under the receiver operating characteristic curve [AUC] = 0.92), providing superior fit compared with other models, including one with only ocular variables (NRI&#xa0;=&#xa0;0.34; P < 0.001; AUC = 0.87, &#x394;AUC 0.05 &#xb1; 0.005; P < 0.001).<br><br>CONCLUSION: Genetic variants and family history provided additional discrimination for predicting progression to AAMD, after accounting for baseline macular status and other covariates.},
}
@article {pmid37437816,
year = {2023},
author = {Patel, AK and Vadrale, AP and Singhania, RR and Chen, CW and Chang, JS and Dong, CD},
title = {Enhanced mixotrophic production of lutein and lipid from potential microalgae isolate Chlorella sorokiniana C16.},
journal = {Bioresource technology},
volume = {386},
number = {},
pages = {129477},
doi = {10.1016/j.biortech.2023.129477},
pmid = {37437816},
issn = {1873-2976},
mesh = {*Chlorella ; Lutein ; *Microalgae ; Biomass ; Lipids ; },
abstract = {The current work aims to isolate high lutein-producing microalgae and maximize lutein production under a sustainable lutein-lipid biorefinery scheme. Lutein reduces retinitis, macular degeneration risk and improves eye health. An effective bioprocess design optimized nutrients, temperature, light, and salinity for biomass and lutein yield enhancement. 3X macro/micronutrients maximally enhanced biomass and lutein yields, 5.2 g/Land 71.13 mg/L. Temperature 32 °C exhibited maximum 17.4 mg/g lutein content and 10 k lux was most favorable for growth and lutein yield (15.47 mg/g). A 25% seawater addition led maximum of 21-27% lipid that could be used for biodiesel. Isolate was identified as Chlorella sorokiniana C16, which exhibited one of the highest lutein yields reported among recent studies, positioning it as a promising candidate for commercial lutein production. This study provides valuable insights into an effective bioprocess design and highlights the C16 strain potential as a sustainable platform for high-value lutein production under a biorefinery scheme.},
}
@article {pmid37437714,
year = {2023},
author = {Smith, SE and Lynch, AM and Auer, EA and Bol, KA and Christopher, KL and Mandava, N and Patnaik, JL},
title = {Visual Functioning and Mortality of Age-Related Macular Degeneration Patients in a Colorado Cohort.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {11},
pages = {982-989},
pmid = {37437714},
issn = {2468-6530},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; UM1 TR004399/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy ; Colorado/epidemiology ; Angiogenesis Inhibitors ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration ; },
abstract = {OBJECTIVE: To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and mortality in patients with various stages of age-related macular degeneration (AMD).<br><br>DESIGN: Observational cohort study.<br><br>PARTICIPANTS: Patients with AMD enrolled in the University of Colorado AMD Registry between July 9, 2014 and December 31, 2021 were included.<br><br>METHODS: Age-related macular degeneration cases were classified into early AMD, intermediate AMD, geographic atrophy, neovascular AMD, or both advanced types of AMD (neovasuclar and geographic atrophy both present) using multimodal imaging and the Beckman and Classification of Atrophy Meetings criteria. Visual Function Questionnaire&#xa0;-25 composite and subscale scores at the time of study enrollment were calculated. Cox proportional hazards modeling was used to assess time to event for mortality utilizing univariate and multivariable models, which adjusted for all variables significantly associated with mortality. The measures of association were hazard ratios (HRs) and 95% confidence intervals (CIs).<br><br>MAIN OUTCOME MEASURES: All-cause mortality statistics were obtained through a collaborative agreement with the Colorado Department of Public Health and Environment. Death rates through October 19, 2022 were compared by demographics and potential confounders.<br><br>RESULTS: Analysis was completed on a cohort of 876 patients, of which 180 (20.6%) died during the follow-up period. Average follow-up time for this cohort was 52.5 (standard deviation: 26.6) months. In univariate analysis, composite VFQ-25 score and all subscale scores aside from ocular pain were significantly associated with time to mortality. Additionally, age, AMD category, marital status, history of smoking, and multiple chronic comorbid conditions were significantly associated with time to mortality. In multivariable analysis, for each 10-point increase in a patient's VFQ-25 scores for general health and driving, the risk of death decreased with HR of 0.85 (95% CI: 0.80, 0.91; P < 0.0001) and 0.92 (95% CI: 0.87, 0.97; P&#xa0;= 0.005), respectively. Composite and other subscale scores were not significantly associated with mortality after adjusting for confounding variables.<br><br>CONCLUSIONS: This cohort of AMD patients had a 20% rate of death in the 52.5-month average follow-up time. Better general health and ability to drive, as measured by the VFQ-25, were each separately associated with significantly lower risk of death among individuals with AMD.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid37437713,
year = {2023},
author = {Corvi, F and Corradetti, G and Laiginhas, R and Liu, J and Gregori, G and Rosenfeld, PJ and Sadda, SR},
title = {Comparison between B-Scan and En Face Images for Incomplete and Complete Retinal Pigment Epithelium and Outer Retinal Atrophy.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {11},
pages = {999-1009},
doi = {10.1016/j.oret.2023.07.003},
pmid = {37437713},
issn = {2468-6530},
mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; Retrospective Studies ; Cross-Sectional Studies ; Fluorescein Angiography ; *Retinal Degeneration/pathology ; Atrophy ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: To evaluate and compare the detection of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA) assessed on OCT B-scans versus persistent choroidal hypertransmission defects (hyperTDs) assessed by en face choroidal OCT images.<br><br>DESIGN: Retrospective, cross-sectional study.<br><br>PARTICIPANTS: Patients with late atrophic age-related macular degeneration imaged on the same day using both Spectralis OCT and Cirrus OCT.<br><br>MAIN OUTCOME MEASURE: Agreement between the B-scan and en face OCT for the detection of hyperTDs, cRORA, and iRORA.<br><br>METHODS: Two independent graders examined en face OCT and structural OCT to determine the presence and location of hyperTDs, iRORA, and cRORA.<br><br>RESULTS: A total of 239 iRORA and cRORA lesions were detected on the B-scans, and 249 hyperTD lesions were identified on the en face OCT images. There was no significant difference (P&#xa0;= 0.88) in the number of lesions. There was no significant difference in the 134 cRORA lesions identified on B-scans and the 131 hyperTDs detected on en face OCT images (P&#xa0;= 0.13). A total of 105 iRORA lesions were identified by B-scan assessment; however, 50 of these iRORA lesions met the criteria for persistent hyperTDs on en face OCT images (P < 0.001). When considering the topographic correspondence between B-scan and en face OCT detected lesions, the mean percentage of agreement between B-scan detection of cRORA lesions with en face OCT detection was 97.6 % (P&#xa0;= 0.13).<br><br>CONCLUSIONS: We observed high overall agreement between cRORA lesions identified on B-scans and persistent hyperTDs identified on en face OCT. However, en face imaging was able to detect iRORA lesions that had a greatest linear dimension &#x2265; 250 &#x3bc;m in a nonhorizontal en face dimension.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37436898,
year = {2023},
author = {Sun, RX and Zhu, HJ and Zhang, YR and Wang, JN and Wang, Y and Cao, QC and Ji, JD and Jiang, C and Yuan, ST and Chen, X and Liu, QH},
title = {ALKBH5 causes retinal pigment epithelium anomalies and choroidal neovascularization in age-related macular degeneration via the AKT/mTOR pathway.},
journal = {Cell reports},
volume = {42},
number = {7},
pages = {112779},
doi = {10.1016/j.celrep.2023.112779},
pmid = {37436898},
issn = {2211-1247},
mesh = {Animals ; Mice ; *Choroidal Neovascularization/metabolism ; Endothelial Cells/metabolism ; *Macular Degeneration/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Retinal Pigment Epithelium/metabolism ; TOR Serine-Threonine Kinases/metabolism ; *AlkB Homolog 5, RNA Demethylase/metabolism ; },
abstract = {Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N[6]-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.},
}
@article {pmid37434849,
year = {2023},
author = {Xia, Q and Li, J and Zhang, L and Zhou, Y and Yang, Z and Xie, J},
title = {Increasing autophagy ameliorates all-trans-retinal-activated NLRP3 inflammasomes in human THP-1 macrophages.},
journal = {American journal of translational research},
volume = {15},
number = {6},
pages = {4380-4389},
pmid = {37434849},
issn = {1943-8141},
abstract = {OBJECTIVE: Severe inflammation, mediated by innate immune sensors, can be observed in the retina and is considered to play an important role in the pathogenesis of retinal degeneration caused by all-trans-retinal (atRAL). However, the underlying mechanism thereof remains elusive. This study investigated the effects of atRAL on the macrophage cell line THP-1 and determined the underlying signaling pathway through pharmacological and genetical manipulation.<br><br>METHODS: The cytotoxicity of atRAL in THP-1 macrophage cells was assessed using the cell counting kit-8 (CCK-8) assay, and mature IL-1&#x3b2; was detected by enzyme-linked immunosorbent assay (ELISA). We measured levels of NLRP3 and cleaved caspase-1 by western blotting to evaluate the activation of NLRP3 inflammasomes. Oxidative stress was validated by measuring mitochondria-associated reactive oxygen species (ROS) with MitoSOX[TM] Red staining. Autophagy was assessed with the LC3BII turnover assay and tandem mCherry-eGFP-LC3B fluorescence microscopy.<br><br>RESULTS: The maturation and release of IL-1&#x3b2; were regulated by the activation of the NLRP3 inflammasome. Mitochondria-associated ROS were involved in the regulation of NLRP3 inflammasome activation and caspase-1 cleavage. In addition, atRAL functionally activated autophagy in THP-1 cells, and atRAL-induced NLRP3 inflammasome activation was suppressed by autophagy.<br><br>CONCLUSIONS: atRAL activates both the NLRP3 inflammasome and autophagy in THP-1 cells, and the increasing level of autophagy leads to the inhibition of excessive NLRP3 inflammasome activation. These findings shed new light on the pathogenesis of age-related retinal degeneration.},
}
@article {pmid37433077,
year = {2023},
author = {Kamal, KM},
title = {The role of managed care professionals in the management of neovascular age-related macular degeneration and diabetic macular edema.},
journal = {The American journal of managed care},
volume = {29},
number = {6 Suppl},
pages = {S90-S95},
doi = {10.37765/ajmc.2023.89385},
pmid = {37433077},
issn = {1936-2692},
mesh = {Humans ; *Diabetic Retinopathy/complications/drug therapy ; *Macular Edema/drug therapy ; Drug Utilization ; Health Care Costs ; Managed Care Programs ; *Diabetes Mellitus ; },
abstract = {Managed care professionals play a significant role in the management of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) through formulary management and drug utilization strategies. These strategies are designed to improve access to affordable care and minimize medical costs to both patients and payers. Preserving vision in patients with nAMD and DME is key to improving clinical outcomes and reducing the risk of comorbid conditions, such as depression. With the approval of new intravitreal treatment options, managed care professionals must stay up to date with evidence-based guidelines as well as the addition of cost-effective treatments to drug formularies to better manage health care resources and improve patient outcomes.},
}
@article {pmid37433076,
year = {2023},
author = {Almony, A},
title = {Treatment approaches for neovascular age-related macular degeneration and diabetic macular edema.},
journal = {The American journal of managed care},
volume = {29},
number = {6 Suppl},
pages = {S81-S89},
doi = {10.37765/ajmc.2023.89386},
pmid = {37433076},
issn = {1936-2692},
mesh = {Humans ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy/etiology ; Ambulatory Care Facilities ; Cost of Illness ; Intravitreal Injections ; *Diabetes Mellitus ; },
abstract = {Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) can cause substantial disease burden for patients. Several organizations have published clinical guidelines on appropriate diagnosis and treatment recommendations to alleviate this burden. Treatment approaches include both nonpharmacologic methods and pharmacologic therapies, with anti-vascular endothelial growth factor (VEGF) therapy being the standard of care. Anti-VEGF therapy is an effective treatment option for both nAMD and DME; however, long-term patient compliance may be reduced due to the burden of costs, monthly intravitreal injections, and repeat clinic visits to assess clinical response parameters. Emerging treatments and dosing strategies aim to decrease treatment burden and increase patient safety. Retina specialists can play a key role in improving the management of both nAMD and DME by incorporating patient-specific treatment strategies tailored to improve clinical outcomes. Enhanced knowledge of retinal disease therapies will allow clinicians to optimize evidence-based treatment strategies to improve clinical outcomes for their patients.},
}
@article {pmid37433075,
year = {2023},
author = {Almony, A},
title = {Disease burden of neovascular age-related macular degeneration and diabetic macular edema.},
journal = {The American journal of managed care},
volume = {29},
number = {6 Suppl},
pages = {S75-S80},
doi = {10.37765/ajmc.2023.89387},
pmid = {37433075},
issn = {1936-2692},
mesh = {Aged ; Humans ; *Diabetic Retinopathy/complications/drug therapy ; *Macular Edema/drug therapy/etiology ; Vascular Endothelial Growth Factor A ; Cost of Illness ; Inflammation ; *Diabetes Mellitus ; },
abstract = {Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are the leading causes of vision impairment in elderly patients and people living with diabetes, respectively. Common features of nAMD and DME include increased vascular permeability, inflammation, and neovascularization. Intravitreal administration of vascular endothelial growth factor (VEGF) inhibitors has been the gold standard for treating retinal diseases, and numerous studies have demonstrated their ability to stabilize disease progression and improve visual acuity. However, many patients struggle with the burden of frequent injections, experience a suboptimal treatment response, or lose vision over time. For these reasons, the outcomes of anti-VEGF treatment are often worse in the real-world compared with clinical trials.},
}
@article {pmid37432847,
year = {2023},
author = {Hwang, S and Kang, SW and Kim, SJ and Lee, KN and Han, K and Lim, DH},
title = {Diabetes-Related Risk Factors for Exudative Age-Related Macular Degeneration: A Nationwide Cohort Study of a Diabetic Population.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {10},
pages = {10},
pmid = {37432847},
issn = {1552-5783},
mesh = {Humans ; Middle Aged ; *Diabetic Retinopathy/epidemiology/etiology ; Cohort Studies ; Risk Factors ; Insulin/therapeutic use ; *Macular Degeneration/epidemiology/etiology ; *Diabetes Mellitus/epidemiology ; },
abstract = {PURPOSE: The purpose of this study was to identify diabetes-related risk factors for exudative age-related macular degeneration (AMD).<br><br>METHODS: This was a nationwide population-based cohort study using authorized clinical data provided by the Korean National Health Insurance Service. A total of 1,768,018 participants with diabetes over 50 years of age participated in the Korean National Health Screening Program between 2009 and 2012. Data on covariates, including age, sex, income level, systemic comorbidities, behavioral factors, and diabetes-related parameters, including duration of diabetes, use of insulin for diabetes control, number of oral hypoglycemic agents used, and accompanying vision-threatening diabetic retinopathy, were collected from health screening results and claims data. Patients were followed up until December 2018. Incident cases of exudative AMD were identified using registered diagnostic codes from the claims data. The prospective association of diabetes-related parameters with incident exudative AMD was investigated using the multivariable-adjusted Cox proportional hazard model.<br><br>RESULTS: During an average follow-up period of 5.93 years, 7331 patients were newly diagnosed with exudative AMD. Compared to those who had diabetes for less than 5 years, individuals with diabetes for 5 years or more had a greater risk of future exudative AMD development, with a hazard ratio (95% confidence interval) of 1.13 (1.07-1.18) in the fully adjusted model. Use of insulin for diabetes control and the presence of vision-threatening diabetic retinopathy were also associated with an increased risk of exudative AMD with a hazard ratio (95% confidence interval) of 1.16 (1.07-1.25) and 1.40 (1.23-1.61), respectively.<br><br>CONCLUSIONS: A longer duration of diabetes, administration of insulin for diabetes control, and comorbid vision-threatening diabetic retinopathy were associated with an increased risk of developing exudative AMD.},
}
@article {pmid37432187,
year = {2023},
author = {Wu, Y and Xie, Y and Yuan, Y and Xiong, R and Hu, Y and Ning, K and Ha, J and Wang, W and Han, X and He, M},
title = {The Mediterranean Diet and Age-Related Eye Diseases: A Systematic Review.},
journal = {Nutrients},
volume = {15},
number = {9},
pages = {},
pmid = {37432187},
issn = {2072-6643},
support = {82000901, 82101171//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Angiogenesis Inhibitors ; *Diet, Mediterranean ; Prospective Studies ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; *Glaucoma/epidemiology/prevention &amp; control ; *Cataract/epidemiology/prevention &amp; control ; *Diabetic Retinopathy/epidemiology/prevention &amp; control ; },
abstract = {The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR) and dry eye syndrome (DES). In this study, we systematically reviewed studies in the literature that had reported associations between adherence to the MD and the five above-mentioned AREDs. Randomized controlled trials as well as prospective and retrospective observational studies were included; 1164 studies were identified, of which 1, 2, 9, 2 and 4 studies met our eligibility criteria for cataract, glaucoma, AMD, DR, and DES, respectively. According to these studies, higher MD adherence was associated with reduced risks of incident DR, incident AMD and progression to late AMD, but whether early and neovascular AMD could be alleviated remained to be debated. The results regarding the effects of the MD on DES were mixed, with three studies reporting an associations between MD and decreased severity or incidence of DES, whereas one study reported the opposite. No significant associations were observed between the MD and cataract or glaucoma. Generally, convincing evidence suggested a protective effect of the MD against AMD and DR. However, the evidence for cataract, glaucoma, and DES was less conclusive, and high-quality studies are needed for comprehensive evaluations of the potential benefits of MD on these eye diseases.},
}
@article {pmid37430077,
year = {2023},
author = {Brown, GC and Brown, MM and Gierhart, D and Olk, RJ},
title = {Prevention Surpasses Treatment: 5-year Follow-Up, Cost-Utility, and Cost-Benefit of Zeaxanthin Therapy for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2583-2608},
pmid = {37430077},
issn = {2193-8245},
abstract = {INTRODUCTION: Oral administration of zeaxanthin (Zx) 20 mg daily in patients with unilateral neovascular age-related macular degeneration (nAMD) treated with triple therapy (photodynamic therapy/intravitreal bevacizumab/intravitreal dexamethasone) reduced fellow-eye 2-year nAMD incidence from 23 to 6% (p = 0.02) in a prior clinical trial. We questioned the long-term benefit and thus analyzed case-control 5-year patient data of trial participants and additional participants with 5-year follow-up, also performing cost-utility and cost-benefit analyses.<br><br>METHODS: Consecutive, unilateral nAMD patient outcomes for those taking 20&#xa0;mg Zx supplementation orally for&#x2009;&#x2265;&#x2009;5&#xa0;years were compared with the Comparison of AMD Treatments Trials (CATT) 5-year historical controls for fellow-eye nAMD conversion. Eleven-year mean life expectancy, cost-utility and cost-benefit models were undertaken employing a 3% discount rate and 2020 US real dollars.<br><br>RESULTS: Among 227 consecutive patients with nAMD/Zx-supplementation, 202 (90%) had 5-year follow-up. The fellow-eye nAMD 5-year conversion incidence using a Kaplan-Meier cumulative event estimate was 22% (49/227), versus 48% (167/348) with CATT control data (p&#x2009;<&#x2009;0.0001). An 11-year cost-utility model with estimates for years 6-11 demonstrated a 0.42 (7.7%) QALY (quality-adjusted life-year) gain, including 3&#xa0;months of life saved per patient due to decreased nAMD fellow-eye conversion. This yielded a direct ophthalmic medical cost perspective, incremental cost-utility ratio (CUR) of -$576/QALY and a societal cost perspective CUR of -$125,071/QALY. Zx supplementation for all 2020 US unilateral nAMD cases would have theoretically saved society, primarily patients, $6.0 billion over 11&#xa0;years, a 1531% return on investment (ROI), or 31.3% annual ROI, on Zx costs.<br><br>CONCLUSIONS: Oral zeaxanthin supplementation for unilateral nAMD patients appears to decrease fellow-eye long-term incidence and is cost-effective and financially rewarding. It is dominant vs. no supplementation in patients presenting with unilateral nAMD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01527435.},
}
@article {pmid37429701,
year = {2024},
author = {Bikbov, MM and Kazakbaeva, GM and Holz, FG and Panda-Jonas, S and Gilemzianova, LI and Khakimov, DA and Jonas, JB},
title = {Intravitreal panitumumab and myopic macular degeneration.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {6},
pages = {859-864},
doi = {10.1136/bjo-2023-323383},
pmid = {37429701},
issn = {1468-2079},
mesh = {Humans ; *Panitumumab/administration &amp; dosage/therapeutic use ; *Intravitreal Injections ; Female ; Male ; Aged ; Middle Aged ; *Visual Acuity/physiology ; Myopia, Degenerative/drug therapy/physiopathology ; Tomography, Optical Coherence ; Treatment Outcome ; Macular Degeneration/drug therapy ; ErbB Receptors/antagonists &amp; inhibitors ; Dose-Response Relationship, Drug ; Follow-Up Studies ; },
abstract = {BACKGROUND: In experimental studies, intravitreally applied antibodies against epidermal growth factor (EGF), EGF family members (amphiregulin, neuregulin-1, betacellulin, epigen, epiregulin) and against the EGF receptor (EGFR) were associated with a reduction in lens-induced axial elongation and decrease in physiological eye elongation in guinea pigs and in non-human primates. Here, we investigated the intraocular tolerability and safety of a fully human monoclonal IgG2-antibody against EGFR, already in clinical use in oncology, as a potential future therapeutic approach for axial elongation in adult eyes with pathological myopia.<br><br>METHODS: The clinical, monocentre, open-label, multiple-dose, phase-1 study included patients with myopic macular degeneration of stage 4, who received intravitreal injections of panitumumab in various doses and in intervals ranging between 2.1 months and 6.3 months.<br><br>RESULTS: The study included 11 patients (age:66.8&#xb1;6.3 years), receiving panitumumab injections in doses of 0.6&#x2009;mg (4 eyes; 1&#xd7;1 injection, 3&#xd7;2 injections), 1.2&#x2009;mg (4 eyes; 1&#xd7;1 injection, 2&#xd7;2 injections, 1&#xd7;3 injections) and 1.8&#x2009;mg (3 eyes; 1&#xd7;1 injection, 2&#xd7;2 injections), respectively. None of the participants showed treatment-emergent systemic adverse events or intraocular inflammatory reactions. Best-corrected visual acuity (1.62&#xb1;0.47 logarithm of the minimal angle of resolution (logMAR) vs 1.28&#xb1;0.59 logMAR; p=0.08) and intraocular pressure (13.8&#xb1;2.4&#x2009;mm Hg vs 14.3&#xb1;2.6&#x2009;mm Hg; p=0.20) remained unchanged. In nine patients with a follow-up of >3 months (mean:6.7&#xb1;2.7 months), axial length did not change significantly (30.73&#xb1;1.03&#x2009;mm vs 30.77&#xb1;1.19&#x2009;mm; p=0.56).<br><br>CONCLUSIONS: In this open-labelled, phase-1 study with a mean follow-up of 6.7 months, panitumumab repeatedly administered intravitreally up to a dose of 1.8&#x2009;mg was not associated with intraocular or systemic adverse effects. During the study period, axial length remained unchanged.<br><br>TRIAL REGISTRATION NUMBER: DRKS00027302.},
}
@article {pmid37428130,
year = {2023},
author = {Wu, Z and Hadoux, X and Jannaud, M and Martin, KR and van Wijngaarden, P and Guymer, RH},
title = {Systematic Underestimation of Visual Sensitivity Loss on Microperimetry: Implications for Testing Protocols in Clinical Trials.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {7},
pages = {11},
pmid = {37428130},
issn = {2164-2591},
mesh = {Humans ; Reproducibility of Results ; Vision Disorders ; Visual Acuity ; *Visual Field Tests/methods ; *Visual Fields ; Clinical Trial Protocols as Topic ; },
abstract = {PURPOSE: To examine whether systematic changes in visual sensitivity measurements on microperimetry occur over tests within the same session and whether these changes vary according to the level of visual sensitivity loss.<br><br>METHODS: Eighty individuals with glaucoma or atrophic age-related macular degeneration underwent three microperimetry tests in one eye during one session using the 4-2 staircase strategy. Changes in mean sensitivity (MS) and pointwise sensitivity (PWS) between the first and second test pairs were examined, with PWS was examined separately based on its average value across the three tests in 6-dB bins. The coefficient of repeatability (CoR) for MS between each sequential test pair was also calculated.<br><br>RESULTS: There was a significant decline in MS from the first to second test (P = 0.001), but no significant difference in MS was seen between the second and third tests (P = 0.562). This significant decline in the first test pair was observed in locations with an average PWS of <6 dB or between 6 to 12 dB and between 12 to 18 dB (P < 0.001), but not for all other average PWS bins (P &#x2265; 0.337). The CoR of MS was significantly lower in the second compared to the first test pair (1.4 dB and 2.5 dB, respectively; P < 0.001).<br><br>CONCLUSIONS: The 4-2 staircase strategy conventionally used on microperimetry testing systematically underestimates visual sensitivity loss on the first test.<br><br>TRANSLATIONAL RELEVANCE: The consistency and accuracy of visual sensitivity measurements on microperimetry in clinical trials could be markedly improved by using estimates from an initial test to seed subsequent tests and excluding this first test from analyses.},
}
@article {pmid37427513,
year = {2023},
author = {Agarkov, NM and Gurko, TS and Lev, IV},
title = {[The social and medical aspects of falls in elderly and senile age under eyesight deficiency].},
journal = {Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsiny},
volume = {31},
number = {3},
pages = {400-404},
doi = {10.32687/0869-866X-2023-31-3-400-404},
pmid = {37427513},
issn = {0869-866X},
mesh = {Aged ; Male ; Humans ; Female ; Aged, 80 and over ; Middle Aged ; *Diabetic Retinopathy/epidemiology ; Accidental Falls ; Retrospective Studies ; Aging ; *Cataract ; *Glaucoma ; *Macular Degeneration/epidemiology/complications ; Vision Disorders/complications ; },
abstract = {The aging of population is accompanied by simultaneous increasing of rate of age-associated ophthalmic diseases resulting in vision decreasing. However, visual impairment in elderly and senile age is rarely considered in the epidemiology of falls in these groups. The purpose of the study is to investigate medical social aspects of falls in older age groups with visual impairment. The retrospective methodology was applied to study falls in 4832 elderly and senile patients with visual impairment due to cataract glaucoma, diabetic retinopathy and age-related macular degeneration. The high incidence of falls in men and women aged 80 and older, amounting to 82.6 and 125.7 cases per 1000 of population of corresponding age respectively was established. The falls in elderly patients with low vision is more often registered in case of diabetic retinopathy than of glaucoma, cataract and age-related macular degeneration without significant differences at the age 50-59 years and 60-69 years. The diabetic retinopathy is the most common cause of falls requiring hospitalization in all age groups. To In reducing prevalence of falls and resulted hospitalization, to optimize traumatological care of patients of older age groups, the priority is for early identification and treatment of people with diabetic retinopathy.},
}
@article {pmid37425528,
year = {2023},
author = {Cheng, AM and Joshi, S and Banoub, RG and Saddemi, J and Chalam, KV},
title = {Faricimab Effectively Resolves Intraretinal Fluid and Preserves Vision in Refractory, Recalcitrant, and Nonresponsive Neovascular Age-Related Macular Degeneration.},
journal = {Cureus},
volume = {15},
number = {6},
pages = {e40100},
pmid = {37425528},
issn = {2168-8184},
abstract = {PURPOSE: To evaluate the functional and anatomic outcomes of faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) who are unresponsive to other anti-vascular endothelial growth factor (VEGF) therapies.<br><br>METHODS: A retrospective interventional study was conducted on patients with refractory nAMD who were initially treated with intravitreal bevacizumab, ranibizumab, or aflibercept. These patients were switched to monthly faricimab injections. The central subfield thickness (CST), intraretinal fluid (IRF)&#xa0;or subretinal fluid (SRF) height, and visual acuities were compared before and after faricimab treatment.<br><br>RESULTS: A total of 13 eyes (eight right eyes and five left eyes) from 11 patients were followed for 10.4 &#xb1; 6.9 months after bevacizumab treatment and 40.3 &#xb1; 28.7 months after aflibercept treatment before switching to faricimab. The follow-up time for patients receiving a mean number of 3.7 &#xb1; 1.3 faricimab injections was 3.4 &#xb1; 1.2 months. The overall median CST was reduced by 18&#xb5;m (p=0.001) from 342&#xb5;m to 318&#xb5;m, along with a reduction of 89&#xb5;m (p=0.03) in IRF/SRF height from 97&#xb5;m to 40&#xb5;m. Following three consecutive injections, the CST showed a significant reduction of 21.5&#xb5;m (p=0.004) from 344&#xb5;m to 322.5&#xb5;m, and IRF/SRF height was reduced by 89&#xb5;m (p=0.03) from 104&#xb5;m to 18.5&#xb5;m. The intraretinal fluid size decreased and leakage stopped, as seen on fluorescein angiography. Visual acuity remained stable after switching to faricimab treatment (0.59 &#xb1; 0.45 logMAR vs 0.58 &#xb1; 0.45 logMAR, p=1).<br><br>CONCLUSIONS: Faricimab has proven to be an effective treatment for nAMD patients resistant to other anti-VEGF agents. It demonstrates significant anatomical improvement and vision preservation in this challenging patient population.},
}
@article {pmid37425325,
year = {2023},
author = {Wang, Z and Lim, G and Ng, WY and Tan, TE and Lim, J and Lim, SH and Foo, V and Lim, J and Sinisterra, LG and Zheng, F and Liu, N and Tan, GSW and Cheng, CY and Cheung, GCM and Wong, TY and Ting, DSW},
title = {Synthetic artificial intelligence using generative adversarial network for retinal imaging in detection of age-related macular degeneration.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1184892},
pmid = {37425325},
issn = {2296-858X},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is one of the leading causes of vision impairment globally and early detection is crucial to prevent vision loss. However, the screening of AMD is resource dependent and demands experienced healthcare providers. Recently, deep learning (DL) systems have shown the potential for effective detection of various eye diseases from retinal fundus images, but the development of such robust systems requires a large amount of datasets, which could be limited by prevalence of the disease and privacy of patient. As in the case of AMD, the advanced phenotype is often scarce for conducting DL analysis, which may be tackled via generating synthetic images using Generative Adversarial Networks (GANs). This study aims to develop GAN-synthesized fundus photos with AMD lesions, and to assess the realness of these images with an objective scale.<br><br>METHODS: To build our GAN models, a total of 125,012 fundus photos were used from a real-world non-AMD phenotypical dataset. StyleGAN2 and human-in-the-loop (HITL) method were then applied to synthesize fundus images with AMD features. To objectively assess the quality of the synthesized images, we proposed a novel realness scale based on the frequency of the broken vessels observed in the fundus photos. Four residents conducted two rounds of gradings on 300 images to distinguish real from synthetic images, based on their subjective impression and the objective scale respectively.<br><br>RESULTS AND DISCUSSION: The introduction of HITL training increased the percentage of synthetic images with AMD lesions, despite the limited number of AMD images in the initial training dataset. Qualitatively, the synthesized images have been proven to be robust in that our residents had limited ability to distinguish real from synthetic ones, as evidenced by an overall accuracy of 0.66 (95% CI: 0.61-0.66) and Cohen's kappa of 0.320. For the non-referable AMD classes (no or early AMD), the accuracy was only 0.51. With the objective scale, the overall accuracy improved to 0.72. In conclusion, GAN models built with HITL training are capable of producing realistic-looking fundus images that could fool human experts, while our objective realness scale based on broken vessels can help identifying the synthetic fundus photos.},
}
@article {pmid37424318,
year = {2024},
author = {Goudot, MM and Rothschild, PR and Bauters, G and Vagge, A and Miere, A and Souied, EH and Behar-Cohen, F and Bernabei, F},
title = {Multimodal imaging in early onset non-neovascular pigment epithelial detachments.},
journal = {European journal of ophthalmology},
volume = {34},
number = {1},
pages = {NP118-NP122},
doi = {10.1177/11206721231187667},
pmid = {37424318},
issn = {1724-6016},
mesh = {Humans ; Female ; Indocyanine Green ; Cross-Sectional Studies ; Fluorescein Angiography/methods ; *Choroidal Neovascularization/diagnosis ; Tomography, Optical Coherence/methods ; *Retinal Detachment/diagnosis/pathology ; Retinal Pigment Epithelium/pathology ; Fluorescein ; Multimodal Imaging ; Retrospective Studies ; },
abstract = {PURPOSE: To describe multimodal imaging of two cases of bilateral non-vascularized pigment epithelial detachments (PED) in young patients with a long-term follow-up.<br><br>METHODS: A complete ophthalmological examination was performed at each follow-up visit including best corrected visual acuity (BCVA), intraocular pressure, slit lamp examination, spectral domain optical coherence tomography (SD-OCT), fluorescein and indocyanine green angiography, OCT angiography.<br><br>RESULTS: Multimodal imaging of two women presenting avascular PED, aged 43 and 57, respectively, was described. In both patients, SD-OCT revealed a high central macular hyporeflective elevation corresponding with PED. Both patients showed a choroidal layer thicker than 420 &#x3bc;m. Fluorescein and indocyanine green angiography didn't show any choroidal neovascularization either at early or late frames. Cross-sectional and en face optical coherence tomography angiography (OCTA) didn't show any flow beneath the PED. During the follow up period one eye showed a retinal pigment epithelium tear and all eyes showed the presence of apical sub-retinal fluid and hyperreflective material on the top of the PED. None of the two patients showed any sign of atrophy during the follow-up period.<br><br>CONCLUSION: The peculiar characteristics of the presented cases suggest that specific pathogenetic mechanisms, not necessarily related to age related macular degeneration, may play a key role in the development of these lesions. Whether early onset of such drusenoid PED is a specific entity resulting from a genetic deficit of lipid transporters in the RPE is unknown. Further genetic and metabolic studies should be conducted.},
}
@article {pmid37424299,
year = {2024},
author = {Mora, P and Bellucci, C and Radice, LM and Manzotti, F and Gandolfi, S},
title = {Changes in the uninjected contralateral eye after intravitreal brolucizumab for exudative age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {34},
number = {1},
pages = {NP104-NP107},
doi = {10.1177/11206721231187429},
pmid = {37424299},
issn = {1724-6016},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Antibodies, Monoclonal, Humanized/adverse effects ; Receptors, Vascular Endothelial Growth Factor ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Recombinant Fusion Proteins ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: Herein we describe the change in the amount of macular oedema in one eye after contralateral intravitreal brolucizumab injections in a patient with neovascular age-related macular degeneration (nAMD).<br><br>CASE REPORT: A patient with bilateral nAMD underwent intravitreal bevacizumab injections in both eyes with little improvement in the best-corrected visual acuity (BCVA) and central macular exudation. The treatment was switched to aflibercept, but there was incomplete drying of the macula in both eyes. After uneventful cataract extraction, the central macular thickness (CMT) increased markedly in the operated left eye (LE), which was unresponsive to subtenon triamcinolone and further intravitreal aflibercept. Cataract surgery was also performed in the right eye (RE) combined with an intravitreal sustained-release dexamethasone implant. Nevertheless, the CMT increased. Intravitreal brolucizumab injections were performed in the RE with almost complete disappearance of the oedema in the treated eye. Concurrently, the contralateral uninjected eye showed a remarkable decrease in CMT. Five months after the first brolucizumab injection, the macular exudation increased again in both eyes. A second brolucizumab injection was performed in the RE only, and was followed by a prompt reduction in CMT in both the injected RE and uninjected LE.<br><br>CONCLUSIONS: Although contralateral retinal changes have been described for many other vascular endothelial growth factor inhibitors, there is little evidence for brolucizumab. We describe a repeated dose- and time-related effect on the uninjected eye in a case of nAMD.},
}
@article {pmid37422928,
year = {2023},
author = {Anisetti, B and Stewart, MW and Eggenberger, ER and Shourav, MMI and Youssef, H and Elkhair, A and Ertekin-Taner, N and Meschia, JF and Lin, MP},
title = {Age-related macular degeneration is associated with probable cerebral amyloid angiopathy: A case-control study.},
journal = {Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association},
volume = {32},
number = {8},
pages = {107244},
doi = {10.1016/j.jstrokecerebrovasdis.2023.107244},
pmid = {37422928},
issn = {1532-8511},
mesh = {Humans ; Aged ; Aged, 80 and over ; Adult ; Cerebral Hemorrhage/etiology ; Case-Control Studies ; *Siderosis ; Cross-Sectional Studies ; Plaque, Amyloid/complications ; *Cerebral Amyloid Angiopathy/complications/diagnostic imaging/epidemiology ; Magnetic Resonance Imaging/adverse effects ; *Macular Degeneration/diagnostic imaging/epidemiology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common retinal degenerative disorder among older individuals. Amyloid deposits, a hallmark of cerebral amyloid angiopathy (CAA), may be involved in the pathogenesis of AMD. Since amyloid deposits may contribute to the development of both AMD and CAA, we hypothesized that patients with AMD have a higher prevalence of CAA.<br><br>OBJECTIVE: To compare the prevalence of CAA in patients with or without AMD matched for age.<br><br>METHODS: We conducted a cross-sectional, 1:1 age-matched, case-control study of patients &#x2265;40 years of age at the Mayo Clinic who had undergone both retinal optical coherence tomography and brain MRI from 2011 to 2015. Primary dependent variables were probable CAA, superficial siderosis, and lobar and deep cerebral microbleeds (CMBs). The relationship between AMD and CAA was assessed using multivariable logistic regression and was compared across AMD severity (none vs early vs late AMD).<br><br>RESULTS: Our analysis included 256 age-matched pairs (AMD 126, no AMD 130). Of those with AMD, 79 (30.9%) had early AMD and 47 (19.4%) had late AMD. The mean age was 75&#xb1;9 years, and there was no significant difference in vascular risk factors between groups. Patients with AMD had a higher prevalence of CAA (16.7% vs 10.0%, p=0.116) and superficial siderosis (15.1% vs 6.2%, p=0.020), but not deep CMB (5.2% vs 6.2%, p=0.426), compared to those without AMD. After adjusting for covariates, having late AMD was associated with increased odds of CAA (OR 2.83, 95% CI 1.10-7.27, p=0.031) and superficial siderosis (OR 3.40, 95%CI 1.20-9.65, p=0.022), but not deep CMB (OR 0.7, 95%CI 0.14-3.51, p=0.669).<br><br>CONCLUSIONS: AMD was associated with CAA and superficial siderosis but not deep CMB, consistent with the hypothesis that amyloid deposits play a role in the development of AMD. Prospective studies are needed to determine if features of AMD may serve as biomarkers for the early diagnosis of CAA.},
}
@article {pmid37422192,
year = {2023},
author = {Yu, S and Bachmeier, I and Hernandez-Sanchez, J and Garcia Armendariz, B and Ebneter, A and Pauleikhoff, D and Chakravarthy, U and Fauser, S},
title = {Hyperreflective Material Boundary Remodeling in Neovascular Age-Related Macular Degeneration: A Post Hoc Analysis of the AVENUE Trial.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {11},
pages = {990-998},
doi = {10.1016/j.oret.2023.06.024},
pmid = {37422192},
issn = {2468-6530},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Choroidal Neovascularization/diagnosis/drug therapy ; *Macular Degeneration/diagnosis/drug therapy ; Ranibizumab/therapeutic use ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; },
abstract = {OBJECTIVE: To describe the spatial and temporal characteristics of hyperreflective material (HRM) on spectral-domain OCT (SD-OCT) in neovascular age-related macular degeneration (nAMD) during antiangiogenic treatment and explore associations with best-corrected visual acuity (BCVA) and macular atrophy (MA).<br><br>DESIGN: Retrospective regrading of SD-OCT-images from the multicenter, randomized controlled AVENUE trial (NCT02484690, conducted from August 2015 to September 2017).<br><br>PARTICIPANTS: Treatment-naive nAMD patients enrolled from 50 sites in the US.<br><br>METHODS: Retrospective regrading and secondary analysis.<br><br>MAIN OUTCOME MEASURES: Spectral-domain OCT images from 207 study eyes that fit criteria for the present analysis were graded for HRM features, its evolution, and associated hypertransmission into choroid (HTC), a proxy for MA. The appearance of a well-defined hyperreflective inner boundary that separated persistent HRM from the neurosensory retina continuous with the adjacent retinal pigment epithelium layer was defined as hyperreflective material boundary remodeling (HRM-BR). Patterns of HRM composition/evolution were defined as follows: (1) no subretinal HRM at baseline, (2) fully resolved, (3) persistent with complete HRM-BR, or (4) partial/absent HRM-BR. Associations of HRM patterns with BCVA and HTC were analyzed. Predictive factors for complete HRM-BR were explored.<br><br>RESULTS: Of 207 included eyes, subretinal HRM was present in 159 (76.8%) at baseline and persisted until month 9 in 118 (57.0%) eyes. Of these 118 eyes, 44.9% developed complete HRM-BR and had similar BCVA outcomes by month 9 compared with no/fully resolved subretinal HRM. Partial/absent HRM-BR had a strong negative association with BCVA outcome (-6.1 ETDRS letters; P&#xa0;= 0.016) and a higher frequency of intralesional HTC (69.2%) compared with eyes with complete HRM-BR (20.8%) at month 9. Older age (odds ratio [OR], 0.96; P&#xa0;= 0.054) and presence of intralesional HTC (OR, 0.06; P&#xa0;= 0.010) at baseline were associated with lower odds of complete HRM-BR at month&#xa0;9.<br><br>CONCLUSIONS: In nAMD eyes under antiangiogenic treatment, complete HRM-BR occurred frequently and was associated with better BCVA than when HRM-BR was only partial/absent.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37421481,
year = {2024},
author = {Pucchio, A and Krance, SH and Pur, DR and Bhatti, J and Bassi, A and Manichavagan, K and Brahmbhatt, S and Aggarwal, I and Singh, P and Virani, A and Stanley, M and Miranda, RN and Felfeli, T},
title = {Applications of artificial intelligence and bioinformatics methodologies in the analysis of ocular biofluid markers: a scoping review.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {4},
pages = {1041-1091},
pmid = {37421481},
issn = {1435-702X},
mesh = {Humans ; *Artificial Intelligence ; *Computational Biology/methods ; *Biomarkers/blood ; Eye Diseases/diagnosis/genetics ; },
abstract = {PURPOSE: This scoping review summarizes the applications of artificial intelligence (AI) and bioinformatics methodologies in analysis of ocular biofluid markers. The secondary objective was to explore supervised and unsupervised AI techniques and their predictive accuracies. We also evaluate the integration of bioinformatics with AI tools.<br><br>METHODS: This scoping review was conducted across five electronic databases including EMBASE, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from inception to July 14, 2021. Studies pertaining to biofluid marker analysis using AI or bioinformatics were included.<br><br>RESULTS: A total of 10,262 articles were retrieved from all databases and 177 studies met the inclusion criteria. The most commonly studied ocular diseases were diabetic eye diseases, with 50 papers (28%), while glaucoma was explored in 25 studies (14%), age-related macular degeneration in 20 (11%), dry eye disease in 10 (6%), and uveitis in 9 (5%). Supervised learning was used in 91 papers (51%), unsupervised AI in 83 (46%), and bioinformatics in 85 (48%). Ninety-eight papers (55%) used more than one class of AI (e.g. > 1 of supervised, unsupervised, bioinformatics, or statistical techniques), while 79 (45%) used only one. Supervised learning techniques were often used to predict disease status or prognosis, and demonstrated strong accuracy. Unsupervised AI algorithms were used to bolster the accuracy of other algorithms, identify molecularly distinct subgroups, or cluster cases into distinct subgroups that are useful for prediction of the disease course. Finally, bioinformatic tools were used to translate complex biomarker profiles or findings into interpretable data.<br><br>CONCLUSION: AI analysis of biofluid markers displayed diagnostic accuracy, provided insight into mechanisms of molecular etiologies, and had the ability to provide individualized targeted therapeutic treatment for patients. Given the progression of AI towards use in both research and the clinic, ophthalmologists should be broadly aware of the commonly used algorithms and their applications. Future research may be aimed at validating algorithms and integrating them in clinical practice.},
}
@article {pmid37420309,
year = {2023},
author = {Akkan Aydoğmuş, FS and Onwuka, O and Saddemi, J and Lasalle, CC and Ramsey, DJ},
title = {Second eyes to develop neovascular age-related macular degeneration have fewer symptoms and better one-year visual outcomes.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {303},
pmid = {37420309},
issn = {1471-2415},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Retinal Pigment Epithelium ; *Retinal Detachment/drug therapy ; Tomography, Optical Coherence ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Ranibizumab/therapeutic use ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {BACKGROUND: This study compares the visual and anatomical outcomes for the eyes of patients who developed sequential neovascular age-related macular degeneration (nAMD), both at the time of diagnosis and at one year after treatment.<br><br>METHODS: The study comprised a retrospective case series of 52 patients whose eyes were diagnosed sequentially with nAMD. All eyes were treated with three monthly loading doses of anti-vascular endothelial growth factor agents, followed by further intravitreal injections, as required. Baseline characteristics and outcomes at one year after diagnosis and initial treatment were compared between first and second eyes and included visual acuity (VA), central macular thickness (CMT), and pigment epithelial detachment (PED) height on optical coherence tomography (OCT) imaging.<br><br>RESULTS: VA at diagnosis was better for second eyes compared with first eyes to develop nAMD (logMAR 0.68&#x2009;&#xb1;&#x2009;0.51 versus logMAR 0.41&#x2009;&#xb1;&#x2009;0.34, P&#x2009;=&#x2009;0.002) and remained so at one year (logMAR 0.61&#x2009;&#xb1;&#x2009;0.60 versus logMAR 0.42&#x2009;&#xb1;&#x2009;0.37, P&#x2009;=&#x2009;0.041). Similarly, PED height at diagnosis was higher in first eyes (225&#x2009;&#xb1;&#x2009;176&#xa0;&#x3bc;m versus 155&#x2009;&#xb1;&#x2009;144&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.003) and also at one year (188&#x2009;&#xb1;&#x2009;137&#xa0;&#x3bc;m versus 140&#x2009;&#xb1;&#x2009;112&#xa0;&#x3bc;m, P&#x2009;=&#x2009;0.019). Whereas most patients reported symptoms at first eye diagnosis (71.2%), half as many second eyes were symptomatic (28.8%, P&#x2009;<&#x2009;0.001). Significantly more symptomatic first eyes experienced visual distortions (32.4% versus 13.3%) or scotomas (29.4% versus 6.7%), compared with a less specific visual complaint of blurry vision (38.2% versus 80.0%, P&#x2009;=&#x2009;0.006).<br><br>CONCLUSIONS: Compared with first eyes to develop nAMD, second eyes tended to have better vision, smaller PED heights, and fewer symptoms likely because monitoring permitted earlier diagnosis.},
}
@article {pmid37419959,
year = {2024},
author = {Abdolrahimzadeh, S and Zweifel, SA and Di Pippo, M and Bajka, A and Scuderi, G and Lotery, AJ},
title = {Central macular choriocapillaris impairment as a manifestation of microvascular disease in eyes with subretinal drusenoid deposits.},
journal = {Eye (London, England)},
volume = {38},
number = {1},
pages = {173-178},
pmid = {37419959},
issn = {1476-5454},
mesh = {Humans ; Choroid/pathology ; Cross-Sectional Studies ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis ; Retina ; *Retinal Drusen/diagnosis/pathology ; Retinal Vessels ; Tomography, Optical Coherence/methods ; },
abstract = {BACKGROUND/OBJECTIVES: Microvascular alterations and choroidal impairment are emerging as a pathologic pathway in age-related macular degeneration (AMD). This study aimed to evaluate the central macular choriocapillaris (CC) in eyes with subretinal drusenoid deposits (SDD) and the retinal microvasculature in patients with early AMD phenotypes.<br><br>SUBJECTS/METHODS: This was an institutional, multicentric observational cross-sectional study. Ninety-nine eyes of 99 subjects; 33 eyes with SDD only, 33 eyes with conventional drusen (CD) only, and 33 eyes of healthy age-matched subjects were included. Comprehensive ophthalmologic examination and optical coherence tomography angiography (OCTA) was performed. The central macular flow area of the CC was analysed in the SDD group and the vessel density of the retinal superficial capillary plexus (SCP) and deep capillary plexus (DCP) was analysed in the SDD and CD groups using automated OCTA output parameters.<br><br>RESULTS: The flow area of the CC in the SDD group was significantly reduced (p &#x2264; 0.001) with respect to the healthy control group. There was a trend of reduction of vessel density of the SCP and the DCP in the SDD and CD group with respect to controls, although this did not reach statistical significance.<br><br>CONCLUSIONS: OCTA data in the present report corroborate the role of vascular damage in early AMD with CC impairment in the central macular area in eyes with SDD.},
}
@article {pmid37419213,
year = {2023},
author = {Kannan, RM and Pitha, I and Parikh, KS},
title = {A new era in posterior segment ocular drug delivery: Translation of systemic, cell-targeted, dendrimer-based therapies.},
journal = {Advanced drug delivery reviews},
volume = {200},
number = {},
pages = {115005},
doi = {10.1016/j.addr.2023.115005},
pmid = {37419213},
issn = {1872-8294},
mesh = {Humans ; *Dendrimers/metabolism ; Eye/metabolism ; Drug Delivery Systems ; *Eye Diseases/metabolism ; *Macular Degeneration/drug therapy/metabolism ; },
abstract = {Vision impairment and loss due to posterior segment ocular disorders, including age-related macular degeneration and diabetic retinopathy, are a rapidly growing cause of disability globally. Current treatments consist primarily of intravitreal injections aimed at preventing disease progression and characterized by high cost and repeated clinic visits. Nanotechnology provides a promising platform for drug delivery to the eye, with potential to overcome anatomical and physiological barriers to provide safe, effective, and sustained treatment modalities. However, there are few nanomedicines approved for posterior segment disorders, and fewer that target specific cells or that are compatible with systemic administration. Targeting cell types that mediate these disorders via systemic administration may unlock transformative opportunities for nanomedicine and significantly improve patient access, acceptability, and outcomes. We highlight the development of hydroxyl polyamidoamine dendrimer-based therapeutics that demonstrate ligand-free cell targeting via systemic administration and are under clinical investigation for treatment of wet age-related macular degeneration.},
}
@article {pmid37418249,
year = {2023},
author = {Calabrèse, A and Fournet, V and Dours, S and Matonti, F and Castet, E and Kornprobst, P},
title = {A New Vessel-Based Method to Estimate Automatically the Position of the Nonfunctional Fovea on Altered Retinography From Maculopathies.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {7},
pages = {9},
pmid = {37418249},
issn = {2164-2591},
mesh = {Humans ; Fovea Centralis/diagnostic imaging ; *Optic Disk/diagnostic imaging ; Fundus Oculi ; Retinal Vessels/diagnostic imaging ; *Retinal Diseases/diagnostic imaging/pathology ; *Macular Degeneration/diagnostic imaging ; },
abstract = {PURPOSE: The purpose of this study was to validate a new automated method to locate the fovea on normal and pathological fundus images. Compared to the normative anatomic measures (NAMs), our vessel-based fovea localization (VBFL) approach relies on the retina's vessel structure to make predictions.<br><br>METHODS: The spatial relationship between the fovea location and vessel characteristics is learnt from healthy fundus images and then used to predict fovea location in new images. We evaluate the VBFL method on three categories of fundus images: healthy images acquired with different head orientations and fixation locations, healthy images with simulated macular lesions, and pathological images from age-related macular degeneration (AMD).<br><br>RESULTS: For healthy images taken with the head tilted to the side, the NAM estimation error is significantly multiplied by 4, whereas VBFL yields no significant increase, representing a 73% reduction in prediction error. With simulated lesions, VBFL performance decreases significantly as lesion size increases and remains better than NAM until lesion size reaches 200 degrees2. For pathological images, average prediction error was 2.8&#xa0;degrees, with 64% of the images yielding an error of 2.5 degrees or less. VBFL was not robust for images showing darker regions and/or incomplete representation of the optic disk.<br><br>CONCLUSIONS: The vascular structure provides enough information to precisely locate the fovea in fundus images in a way that is robust to head tilt, eccentric fixation location, missing vessels, and actual macular lesions.<br><br>TRANSLATIONAL RELEVANCE: The VBFL method should allow researchers and clinicians to assess automatically the eccentricity of a newly developed area of fixation in fundus images with macular lesions.},
}
@article {pmid37418021,
year = {2023},
author = {Priglinger, CS and Gerhardt, MJ and Rudolph, G and Priglinger, SG and Michalakis, S},
title = {[Gene therapy in ophthalmology].},
journal = {Die Ophthalmologie},
volume = {120},
number = {8},
pages = {867-882},
pmid = {37418021},
issn = {2731-7218},
mesh = {Humans ; *Ophthalmology ; Genetic Vectors/genetics ; Genetic Therapy/methods ; *Retinal Dystrophies/genetics ; Treatment Outcome ; },
abstract = {In 2017 the gene therapy medication voretigene neparvovec-rzyl was approved by the U.S. Food and Drug Administration (FDA) for retinal gene therapy of hereditary retinal dystrophies caused by mutations in the RPE65 gene. Voretigene neparvovec-rzyl is a gene augmentation therapy using an adeno-associated virus-based vector to express a healthy copy of the human RPE65 gene in the patient's retinal pigment epithelial (RPE) cells. The success of gene augmentation therapy in RPE65-linked retinal dystrophy encouraged research activities on the concept of gene supplementation to be extended to nongenetic diseases, such as age-related macular degeneration; however, it also showed that the principle of success cannot be easily extended to other retinal dystrophies. This review article presents the most commonly used principles and technologies of gene therapy and provides an overview of the current challenges and limitations. Furthermore, practice-relevant aspects of the indications and the treatment procedure are discussed. Particular attention is paid to the consideration of disease stages, especially with respect to patient's expectations and the evaluation of treatment success.},
}
@article {pmid37417125,
year = {2023},
author = {Singh, K and Singh, A and Chaudury, P and Jain, D},
title = {Efficacy of low-vision devices in elderly population with age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {7},
pages = {2808-2811},
pmid = {37417125},
issn = {1998-3689},
mesh = {Humans ; Aged ; Middle Aged ; Activities of Daily Living ; Prospective Studies ; Quality of Life ; *Sensory Aids/adverse effects ; *Vision, Low/rehabilitation ; Blindness ; Vision Disorders/complications ; *Wet Macular Degeneration/diagnosis/therapy/complications ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a common cause of blindness, residual damage to macular area in spite of treatment necessitates visual rehabilitation by means of low-vision aids (LVAs).<br><br>METHODS: Thirty patients suffering from different stages of AMD requiring LVAs were included in this prospective study. Patients with nonprogressive, adequately treated AMD were enrolled over a 12-month period, prescribed requisite LVAs and followed-up for a minimum 1-month period. Before and after provision of LVAs, near work efficiencies were evaluated by calculating reading speed as words per minute (wpm) under both photopic and mesopic light conditions, and impact of poor vision on activities of daily living (ADL) was quantified by modified standard questionnaire based on Nhung X et al. questionnaire.<br><br>RESULTS: Of the 30 patients mean studied with mean age of 68 &#xb1; 10 years, 20 patients (66.7%) had dry AMD in better eye and 10 (33.3%) had wet AMD. Post-LVA, near visual acuity improved significantly and all cases were able to read some letters on near vision chart with an average improvement of 2.4 &#xb1; 0.96 lines. The different LVAs prescribed were high plus reading spectacles (up to 10 D) in 23.3%, hand-held magnifiers in 53.3%, base in prisms in 10%, stand held magnifiers in 6.7%, and bar and dome magnifiers in 3.3%.<br><br>CONCLUSION: LVAs are effective in visual rehabilitation in patients with AMD. Self-reported reduction in visual dependency and improvement in vision-related quality of life post use of aids corroborated perceived benefit.},
}
@article {pmid37415944,
year = {2023},
author = {Han, D and He, X},
title = {Screening for biomarkers in age-related macular degeneration.},
journal = {Heliyon},
volume = {9},
number = {7},
pages = {e16981},
pmid = {37415944},
issn = {2405-8440},
abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a significant cause of blindness, initially characterized by the accumulation of sub-Retinal pigment epithelium (RPE) deposits, leading to progressive retinal degeneration and, eventually, irreversible vision loss. This study aimed to elucidate the differential expression of transcriptomic information in AMD and normal human RPE choroidal donor eyes and to investigate whether it could be used as a biomarker for AMD.<br><br>METHODS: RPE choroidal tissue samples (46 Normal samples, 38 AMD samples) were obtained from the GEO (GSE29801) database and screened for differentially expressed genes in normal and AMD patients using GEO2R and R to compare the degree of enrichment of differentially expressed genes in the GO, KEGG pathway. Firstly, we used machine learning models (LASSO, SVM algorithm) to screen disease signature genes and compare the differences between these signature genes in GSVA and immune cell infiltration. Secondly, we also performed a cluster analysis to classify AMD patients. We selected the best classification by weighted gene co-expression network analysis (WGCNA) to screen the key modules and modular genes with the strongest association with AMD. Based on the module genes, four machine models, RF, SVM, XGB, and GLM, were constructed to screen the predictive genes and further construct the AMD clinical prediction model. The accuracy of the column line graphs was evaluated using decision and calibration curves.<br><br>RESULTS: Firstly, we identified 15 disease signature genes by lasso and SVM algorithms, which were associated with abnormal glucose metabolism and immune cell infiltration. Secondly, we identified 52 modular signature genes by WGCNA analysis. We found that SVM was the optimal machine learning model for AMD and constructed a clinical prediction model for AMD consisting of 5 predictive genes.<br><br>CONCLUSION: We constructed a disease signature genome model and an AMD clinical prediction model by LASSO, WGCNA, and four machine models. The disease signature genes are of great reference significance for AMD etiology research. At the same time, the AMD clinical prediction model provides a reference for early clinical detection of AMD and even becomes a future census tool. In conclusion, our discovery of disease signature genes and AMD clinical prediction models may become promising new targets for the targeted treatment of AMD.},
}
@article {pmid37415410,
year = {2024},
author = {Forte, P and Ferro Desideri, L and Manocchio, R and Corazza, P and Traverso, CE and Nicolò, M},
title = {Prechoroidal Cleft Regression After Switch to Intravitreal Brolucizumab.},
journal = {European journal of ophthalmology},
volume = {34},
number = {1},
pages = {NP123-NP126},
doi = {10.1177/11206721231185903},
pmid = {37415410},
issn = {1724-6016},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; },
abstract = {INTRODUCTION: Prechoroidal cleft has been described as a negative prognostic biomarker in patients affected with neovascular age related macular degeneration (nAMD). This peculiar finding consists of a lenticular hyporeflective space located between an outward bowing of Bruch's membrane and the base of a fibrovascular retinal pigment epithelium detachment (PED). Previous studies have reported the partial or complete regression of prechoroidal clefts after treatment with anti-vascular endothelial growth factor (VEGF) injections.<br><br>CASE REPORT: To report a case of complete anatomical regression of an unresponsive prechoroidal cleft after switching to intravitreal Brolucizumab. The patient maintained cleft regression over time and no adverse events (i.e., RPE tears, intraocular inflammation) were observed during follow-up.<br><br>CONCLUSIONS AND IMPORTANCE: To our knowledge, this case report is the first to analyze the clinical efficacy of brolucizumab targeting prechoroidal clefts. Clinical implication and pathogenesis of prechoroidal clefts are yet to be fully elucidated.},
}
@article {pmid37410309,
year = {2023},
author = {Larsen, HO and Grauslund, J and Vergmann, AS},
title = {Efficacy, Durability and Safety of Faricimab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Oedema: Lessons Learned from Registration Trials.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2253-2264},
pmid = {37410309},
issn = {2193-8245},
abstract = {INTRODUCTION: This review aims to assess the efficacy, durability and safety of faricimab-a dual vascular endothelial growth factor and angiopoietin 2 inhibitor-in patients with neovascular age-related macular degeneration (nAMD) and diabetic macula oedema (DMO). It summarises the findings of current studies on faricimab and discusses whether this new drug may fill a gap in current treatment options.<br><br>METHODS: We performed a search of the PubMed, Cochrane, Web of Science and EMBASE databases for publications on faricimab between 29 November 2022 and 10 May 2023, and a search of ClinicalTrials.gov for the protocols on clinical trials for this review. We included clinical trials, case-control studies and observational studies.<br><br>RESULTS: In phase 3 trials of nAMD, the efficacy of faricimab was non-inferior to aflibercept (+ 5.8-6.6 vs.&#x2009;+&#x2009;5.1-6.6 Early Treatment Diabetic Retinopathy Study [ETDRS] letters). At study end, 80% of faricimab-treated patients were on&#x2009;&#x2265;&#x2009;12-week dosing intervals, and 44.9-45.7% of faricimab-treated patients were on 16-week dosing intervals. Total adverse events, as well as serious ocular adverse events, were comparable between groups. In phase 3 trials of DMO, efficacy of faricimab was non-inferior to aflibercept (+&#x2009;10.7-11.8 vs.&#x2009;+&#x2009;10.3-10.9 ETDRS letters). At study end,&#x2009;>&#x2009;70% of patients in the personalised treatment interval faricimab group were on&#x2009;&#x2265;&#x2009;12-week dosing intervals, and 51-53% were on 16-week dosing intervals. Total adverse events were comparable between groups, although the rate of serious ocular adverse events was higher in the faricimab groups than in the aflibercept groups (1.9-3.1% vs. 0.6-1.9%, respectively). In real-world studies of treatment-resistant nAMD or DMO, faricimab demonstrated superior efficacy compared to aflibercept. In a real-world study of mostly previously treated nAMD, faricimab demonstrated some efficacy.<br><br>CONCLUSION: Faricimab demonstrated non-inferior to superior efficacy, strong durability and acceptable safety in treatment-na&#xef;ve nAMD and mostly treatment-na&#xef;ve DMO, as well as superior efficacy in treatment-resistant nAMD and DMO. However, further research is needed on faricimab in real-world settings.},
}
@article {pmid37410279,
year = {2023},
author = {Millar, J and Campbell, S and Duckett, C and Doyle, S and Cole, LM},
title = {MALDI and Trace Metal Analysis in Age-Related Macular Degeneration.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2688},
number = {},
pages = {1-13},
pmid = {37410279},
issn = {1940-6029},
mesh = {Mice ; Animals ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; *Macular Degeneration/metabolism ; *Trace Elements/metabolism ; Metals ; },
abstract = {Age-related macular degeneration (AMD) remains one of the most prevalent causes of blindness throughout the world. Key to prevention of AMD is furthering the understanding of its pathology. In recent years, both the proteins within the innate immune system and essential and non-essential metals have been implicated in the pathology of AMD. Herein, a multidisciplinary and multimodal methodology has been taken to further our understanding of the role of the innate immune proteins and the essential metals within mouse ocular tissue.},
}
@article {pmid37409546,
year = {2023},
author = {Pinelli, R and Ferrucci, M and Biagioni, F and Bumah, V and Scaffidi, E and Puglisi-Allegra, S and Fornai, F},
title = {Curcumin as a Perspective Protection for Retinal Pigment Epithelium during Autophagy Inhibition in the Course of Retinal Degeneration.},
journal = {Current neuropharmacology},
volume = {21},
number = {11},
pages = {2227-2232},
pmid = {37409546},
issn = {1875-6190},
mesh = {Humans ; Retinal Pigment Epithelium/metabolism ; *Retinal Degeneration/metabolism ; *Curcumin/pharmacology/therapeutic use ; Autophagy/physiology ; *Macular Degeneration/drug therapy/metabolism ; Oxidative Stress ; },
abstract = {Defective autophagy in the retinal pigment epithelium (RPE) is involved in retinal degeneration, mostly in the course of age-related macular degeneration (AMD), which is an increasingly prevalent retinal disorder, eventually leading to blindness. However, most autophagy activators own serious adverse effects when administered systemically. Curcumin is a phytochemical, which induces autophagy with a wide dose-response curve, which brings minimal side effects. Recent studies indicating defective autophagy in AMD were analyzed. Accordingly, in this perspective, we discuss and provide some evidence about the protective effects of curcumin in preventing RPE cell damage induced by the autophagy inhibitor 3-methyladenine (3-MA). Cells from human RPE were administered the autophagy inhibitor 3-MA. The cell damage induced by 3-MA was assessed at light microscopy by hematoxylin &amp; eosin, Fluoro Jade-B, and ZO1 immunohistochemistry along with electron microscopy. The autophagy inhibitor 3-MA produces cell loss and cell degeneration of RPE cells. These effects are counteracted dose-dependently by curcumin. In line with the hypothesis that the autophagy machinery is key in sustaining the integrity of the RPE, here we provide evidence that the powerful autophagy inhibitor 3-MA produces dose-dependently cell loss and cell degeneration in cultured RPE cells, while inhibiting autophagy as shown by LC3-II/LC3-I ratio and gold-standard assessment of autophagy through LC3-positive autophagy vacuoles. These effects are prevented dose-dependently by curcumin, which activates autophagy. These data shed the perspective of validating the role of phytochemicals as safe autophagy activators to treat AMD.},
}
@article {pmid37408242,
year = {2023},
author = {Cornebise, C and Perus, M and Hermetet, F and Valls-Fonayet, J and Richard, T and Aires, V and Delmas, D},
title = {Red Wine Extract Prevents Oxidative Stress and Inflammation in ARPE-19 Retinal Cells.},
journal = {Cells},
volume = {12},
number = {10},
pages = {},
pmid = {37408242},
issn = {2073-4409},
mesh = {Humans ; *Wine ; Hydrogen Peroxide ; Oxidative Stress ; Resveratrol/pharmacology ; Inflammation/drug therapy/metabolism ; *Macular Degeneration/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is one of the most commonly occurring ocular diseases worldwide. This degenerative condition affects the retina and leads to the loss of central vision. The current treatments are focused on the late stage of the disease, but recent studies have highlighted the importance and benefits of preventive treatments and how good dietary habits can reduce the risk of progression to an advanced form of the disease. In this context, we studied whether resveratrol (RSV) or a polyphenolic cocktail, red wine extract (RWE), are able to prevent the initiating events of AMD (i.e., oxidative stress and inflammation) in human ARPE-19 retinal pigment epithelial (RPE) cells and macrophages. This study highlights that RWE and RSV can prevent hydrogen peroxide (H2O2) or 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress and can subsequently prevent DNA damage via the inhibition of the ATM (ataxia telangiectasia-mutated)/Chk2 (checkpoint kinase 2) or Chk1 signaling pathways, respectively. Moreover, ELISA assays show that RWE and RSV can prevent the secretion of proinflammatory cytokines in RPE cells and in human macrophages. Interestingly, RWE exhibits a greater protective impact compared to RSV alone, even though RSV was more concentrated when used alone than in the red wine extract. Our results suggest that RWE and RSV may have potential interest as preventive nutritional supplementations against AMD.},
}
@article {pmid37402312,
year = {2023},
author = {Estarreja, J and Mendes, P and Silva, C and Camacho, P and Mateus, V},
title = {Correction: The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis.},
journal = {JMIR research protocols},
volume = {12},
number = {},
pages = {e50411},
doi = {10.2196/50411},
pmid = {37402312},
issn = {1929-0748},
abstract = {[This corrects the article DOI: 10.2196/38658.].},
}
@article {pmid37401371,
year = {2023},
author = {Zhang, KR and Jankowski, CSR and Marshall, R and Nair, R and Más Gómez, N and Alnemri, A and Liu, Y and Erler, E and Ferrante, J and Song, Y and Bell, BA and Baumann, BH and Sterling, J and Anderson, B and Foshe, S and Roof, J and Fazelinia, H and Spruce, LA and Chuang, JZ and Sung, CH and Dhingra, A and Boesze-Battaglia, K and Chavali, VRM and Rabinowitz, JD and Mitchell, CH and Dunaief, JL},
title = {Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells.},
journal = {Disease models &amp; mechanisms},
volume = {16},
number = {7},
pages = {},
pmid = {37401371},
issn = {1754-8411},
support = {S10 OD026860/OD/NIH HHS/United States ; R01 EY029428/EY/NEI NIH HHS/United States ; T32 EY007035/EY/NEI NIH HHS/United States ; T32 GM007388/GM/NIGMS NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; R01 EY032966/EY/NEI NIH HHS/United States ; T32 AI007388/AI/NIAID NIH HHS/United States ; R01 EY026525/EY/NEI NIH HHS/United States ; R01 EY015240/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; *Proteomics ; Oxidative Stress ; Lysosomes/metabolism ; Iron/metabolism ; *Iron Overload/metabolism/pathology ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, the leading cause of blindness in older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured induced pluripotent stem cell-derived RPE cells increased lysosomal abundance, impaired proteolysis and reduced the activity of a subset of lysosomal enzymes, including lysosomal acid lipase (LIPA) and acid sphingomyelinase (SMPD1). In a liver-specific Hepc (Hamp) knockout murine model of systemic iron overload, RPE cells accumulated lipid peroxidation adducts and lysosomes, developed progressive hypertrophy and underwent cell death. Proteomic and lipidomic analyses revealed accumulation of lysosomal proteins, ceramide biosynthetic enzymes and ceramides. The proteolytic enzyme cathepsin D (CTSD) had impaired maturation. A large proportion of lysosomes were galectin-3 (Lgals3) positive, suggesting cytotoxic lysosomal membrane permeabilization. Collectively, these results demonstrate that iron overload induces lysosomal accumulation and impairs lysosomal function, likely due to iron-induced lipid peroxides that can inhibit lysosomal enzymes.},
}
@article {pmid37400599,
year = {2023},
author = {Zarranz-Ventura, J and Escobar-Barranco, JJ and Gómez-Baldó, L and Gallego-Pinazo, R and , },
title = {Reasons for Delayed Anti-VEGF Treatment During COVID-19 Lockdown and Clinical Impact in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2537-2555},
pmid = {37400599},
issn = {2193-8245},
abstract = {INTRODUCTION: Timely anti-vascular endothelial growth factor (VEGF) treatment is crucial for visual function in neovascular age-related macular degeneration (nAMD). The aim of this study was to assess the reasons for anti-VEGF treatment delay during the COVID-19 lockdown and its clinical impact in patients with nAMD.<br><br>METHODS: A retrospective, observational, multicentre study in patients with nAMD treated with anti-VEGF therapy was performed in 16 centres nationwide. Data were retrieved from the FRB Spain registry, patient medical records and administrative databases. Patients were divided into two groups based on whether they received or missed intravitreal injections during the COVID-19 lockdown.<br><br>RESULTS: A total of 302 eyes from 245 patients were included (timely treated group [TTG] 126 eyes; delayed treatment group [DTG] 176 eyes). Visual acuity (VA; ETDRS letters) decreased from baseline to post-lockdown visit in the DTG (mean [standard deviation] 59.1 (20.8) vs. 57.1 (19.7); p&#x2009;=&#x2009;0.020) and was maintained in the TTG (64.2 [16.5] vs. 63.6 [17.5]; p&#x2009;=&#x2009;0.806). VA worsened by an average of -&#xa0;2.0 letters in the DTG and by -&#xa0;0.6 in the TTG (p&#x2009;=&#x2009;0.016). A higher proportion of visits were cancelled due to hospital overload in the TTG (76.5%) than in the DTG (47%), and a higher proportion of patients missed visits in the DTG (53%) than in the TTG (23.5%, p&#x2009;=&#x2009;0.021), with fear of COVID-19 infection being the main reason for missed visits (60%/50%).<br><br>CONCLUSIONS: Treatment delays were caused by both hospital saturation and patients' decision; the latter being mainly driven by fear of COVID-19 infection. These delays had a detrimental effect on the visual outcomes in nAMD patients.},
}
@article {pmid37399252,
year = {2023},
author = {Evers, CD and Chen, L and Messinger, JD and Killingsworth, M and Freund, KB and Curcio, CA},
title = {HISTOLOGY, DIMENSIONS, AND FLUORESCEIN STAINING CHARACTERISTICS OF NODULAR AND CUTICULAR DRUSEN IN AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {10},
pages = {1708-1716},
pmid = {37399252},
issn = {1539-2864},
support = {R01 EY006109/EY/NEI NIH HHS/United States ; },
mesh = {*Macular Degeneration/diagnosis/pathology ; Staining and Labeling ; Fluoresceins ; Humans ; Bruch Membrane/pathology ; Fluorescein Angiography/methods ; Eye Diseases, Hereditary ; *Retinal Drusen/diagnosis/pathology ; },
abstract = {PURPOSE: To enable in vivo analysis of drusen composition and lifecycle, the macular nodular and cuticular drusen were assessed using histology.<br><br>METHODS: Median and interquartile range of base widths of single (nonconfluent) nodular drusen in three sources were determined histologically: 43 eyes of 43 clinically undocumented donors, in an online resource; one eye with punctate hyperfluorescence in fluorescein angiography; and two eyes of one patient with bilateral "starry sky" cuticular drusen. All tissues were processed for high-resolution epoxy-resin histology and for cuticular drusen, transmission electron microscopy.<br><br>RESULTS: All drusen localized between the retinal pigment epithelium basal lamina and inner collagenous layer of the Bruch membrane. They were solid, globular, homogeneously stained with toluidine blue, and uncovered by basal laminar deposit and basal mounds. Median base widths were 13.0 &#xb5; m (Source 1, N = 128 drusen, interquartile range 7.7, 20.0 &#xb5; m), 15.3 &#xb5; m (Source 2, N = 87, interquartile range 10.6, 20.5 &#xb5; m), and 7.3 &#xb5; m (Source 3, N = 78, interquartile range 3.9, 14.1 &#xb5; m).<br><br>CONCLUSION: In three samples, >90% of solitary nodular drusen were <30 &#xb5; m, the visibility threshold in color fundus photography; these drusen are hyperfluorescent in fluorescein angiography. Whether these progress to soft drusen, known as high-risk from epidemiology studies and hypofluorescent, may be determinable from multimodal imaging datasets that include fluorescein angiography.},
}
@article {pmid37398472,
year = {2023},
author = {Advani, J and Corso-Diaz, X and Kwicklis, M and van Asten, F and Ratnapriya, R and Mehta, P and Hamel, A and Mahrotra, S and Segrè, A and Kiel, C and Strunz, T and Weber, B and Chew, E and Hernandez, D and Montezuma, S and Ferrington, D and Swaroop, A},
title = {QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {37398472},
issn = {2693-5015},
support = {P30 EY014104/EY/NEI NIH HHS/United States ; R01 EY031424/EY/NEI NIH HHS/United States ; ZIA EY000450/ImNIH/Intramural NIH HHS/United States ; ZIA EY000546/ImNIH/Intramural NIH HHS/United States ; },
abstract = {DNA methylation (DNAm) provides a crucial epigenetic mark linking genetic variations to environmental influence. We analyzed array-based DNAm profiles of 160 human retinas with co-measured RNA-seq and > 8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 mQTLs and 12,505 eQTLs) and 13,747 eQTMs (DNAm loci affecting gene expression), with over one-third specific to the retina. mQTLs and eQTMs show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration (AMD). Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of AMD pathology by genotype-environment interaction in retina.},
}
@article {pmid37398429,
year = {2023},
author = {Voigt, AP and Mullin, NK and Navratil, EM and Flamme-Wiese, MJ and Lin, LC and Scheetz, TE and Han, IC and Stone, EM and Tucker, BA and Mullins, RF},
title = {GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37398429},
issn = {2692-8205},
support = {F30 EY034009/EY/NEI NIH HHS/United States ; T32 GM139776/GM/NIGMS NIH HHS/United States ; P30 EY025580/EY/NEI NIH HHS/United States ; F30 EY031923/EY/NEI NIH HHS/United States ; R01 EY033331/EY/NEI NIH HHS/United States ; R01 EY033308/EY/NEI NIH HHS/United States ; },
abstract = {Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process. In this study, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We identified genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes. Within the area of neovascularization, endothelial cells were predicted to increase expression of genes related to Rho family GTPase signaling and integrin signaling. Likewise, VEGF and TGFB1 were identified as potential upstream regulators that could drive the observed gene expression changes produced by endothelial and retinal pigment epithelium cells in the macular neovascularization donor. These spatial gene expression profiles were compared to previous single-cell gene expression experiments in human age-related macular degeneration as well as a model of laser-induced neovascularization in mice. As a secondary aim, we also investigated spatial gene expression patterns within the macular neural retina and between the macular and peripheral choroid. We recapitulated previously described regional-specific gene expression patterns across both tissues. Overall, this study spatially analyzes gene expression across the retina, retinal pigment epithelium, and choroid in health and describes a set of candidate molecules that become dysregulated in macular neovascularization.},
}
@article {pmid37398366,
year = {2023},
author = {Hernandez, BJ and Skiba, NP and Plößl, K and Strain, M and Grigsby, D and Kelly, U and Cady, MA and Manocha, V and Maminishkis, A and Watkins, T and Miller, SS and Ashley-Koch, A and Stamer, WD and Weber, BHF and Rickman, CB and Klingeborn, M},
title = {Polarized Desmosome and Hemidesmosome Shedding via Exosomes is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.06.12.544677},
pmid = {37398366},
issn = {2692-8205},
support = {T32 GM136627/GM/NIGMS NIH HHS/United States ; },
abstract = {The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of exosomes that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral exosomes from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of exosome release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in exosome content, including basal-side specific desmosome and hemidesmosome shedding via exosomes. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases, (e.g., AMD) and broadly from blood-CNS barriers in other neurodegenerative diseases.},
}
@article {pmid37395045,
year = {2023},
author = {Carmichael, J and Abdi, S and Balaskas, K and Costanza, E and Blandford, A},
title = {Assessment of optometrists' referral accuracy and contributing factors: A review.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {43},
number = {5},
pages = {1255-1277},
pmid = {37395045},
issn = {1475-1313},
support = {/DH_/Department of Health/United Kingdom ; },
mesh = {Male ; Humans ; Female ; Child ; *Optometrists ; *Optometry ; Retrospective Studies ; Prospective Studies ; State Medicine ; *Glaucoma/diagnosis ; Referral and Consultation ; },
abstract = {PURPOSE: In the UK, ophthalmology has the highest number of outpatient appointments within the National Health Service. False-positive referrals from primary care are one of the main factors contributing to the oversubscription of hospital eye services (HESs). We reviewed the accuracy of referrals originating from primary care optometrists and contributing factors, such as condition type and years since registration.<br><br>RECENT FINDINGS: Of the 31 studies included in the review, 22 were retrospective analyses of referrals and appointments at the HES. Eight were prospective studies, and one used online clinical vignettes. Seven assessed the accuracy of referrals for all ocular conditions. The remaining studies focused on glaucoma (n&#x2009;=&#x2009;11), cataracts (n&#x2009;=&#x2009;7), emergency conditions (n&#x2009;=&#x2009;4), neovascular age-related macular degeneration (n&#x2009;=&#x2009;1) and paediatric binocular vision (n&#x2009;=&#x2009;1). The diagnostic agreement for suspected emergency ocular conditions was the lowest, with only 21.1% of referrals considered to require urgent attention in one study. For glaucoma, the first-visit discharge rate was high (16.7%-48%). Optometrist referral accuracy was overall 18.6% higher than General Medical Practitioners'; however, the two mainly referred different ocular conditions. Female optometrists made more false-positive referrals than males (p&#x2009;=&#x2009;0.008). The proportion of false positives decreased by 6.2% per year since registration (p&#x2009;<&#x2009;0.001).<br><br>SUMMARY: There was significant variation in referral accuracy across different ocular conditions, partly due to differences when defining accurate referrals. Optometrists working in primary care are generally more limited in their resources than the HES. Thus, choosing the cautious option of referral when they are unsure could be in the patients' best interests. The possible effect of increased use of advanced imaging on referrals requires evaluation. Although interventions such as refinement schemes have been put in place, these vary across regions, and their approaches such as virtual referral triaging may reduce unnecessary HES face-to-face appointments and promote communication between primary and secondary care.},
}
@article {pmid37394731,
year = {2024},
author = {Barresi, C and Chhablani, J and Dolz-Marco, R and Gallego-Pinazo, R and Berni, A and Bandello, F and Borrelli, E},
title = {Retinal neurodegeneration in age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {34},
number = {3},
pages = {624-630},
doi = {10.1177/11206721231186166},
pmid = {37394731},
issn = {1724-6016},
mesh = {Humans ; *Macular Degeneration/diagnosis ; *Tomography, Optical Coherence/methods ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Retina/pathology/diagnostic imaging ; },
abstract = {Age-related macular degeneration (AMD) is a complex and multifactorial disease characterized by the damage of the unit comprised of the photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. Although the outer retina appears to be mainly affected in this disorder, several evidences exhibit that also the inner retina may be impaired. In this review we will provide a description of the prominent histologic and imaging findings suggesting an inner retinal loss in these eyes. In details, structural optical coherence tomography (OCT) technology proved either the inner and outer retina is impacted by AMD and that these two impairments are associated. Therefore, the purpose of this review is to provide a description of the role of neurodegeneration in AMD in order to better understand the relationship between neuronal loss and the outer retinal damage in this disease.},
}
@article {pmid37393395,
year = {2024},
author = {Cozzi, M and Monteduro, D and Esposito, RA and Spooner, KL and Fraser-Bell, S and Staurenghi, G and Romano, F and Airaldi, M and Chang, AA and Invernizzi, A},
title = {Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.},
journal = {Eye (London, England)},
volume = {38},
number = {1},
pages = {161-167},
pmid = {37393395},
issn = {1476-5454},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Visual Acuity ; Tomography, Optical Coherence ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {BACKGROUND: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice.<br><br>METHODS: This was a multicentre, retrospective comparative study. Totally, 202 treatment-na&#xef;ve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n&#x2009;=&#x2009;105) or reactive (n&#x2009;=&#x2009;97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated.<br><br>RESULTS: At baseline, the mean [SD] lesion area was 7.24 [5.6]&#x2009;mm[2] in the proactive group and 6.33 [4.8]&#x2009;mm[2] in the reactive group respectively (p&#x2009;=&#x2009;0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5]&#x2009;mm[2] showing a significant reduction compared to the baseline (p&#x2009;<&#x2009;0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0]&#x2009;mm[2] at four years (p&#x2009;<&#x2009;0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions.<br><br>CONCLUSIONS: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.},
}
@article {pmid37392108,
year = {2023},
author = {Calabria, S and Ronconi, G and Dondi, L and Piccinni, C and Pedrini, A and Dondi, L and Dell'Anno, I and Esposito, I and Addesi, A and Staurenghi, G and Bandello, F and Ricci, F and Martini, N},
title = {[The population affected by neovascular age-related macular degeneration and treated with anti-Vegf through Italian administrative healthcare data.].},
journal = {Recenti progressi in medicina},
volume = {114},
number = {7},
pages = {447-461},
doi = {10.1701/4062.40464},
pmid = {37392108},
issn = {2038-1840},
mesh = {Aged ; Aged, 80 and over ; Humans ; Health Care Costs ; Health Expenditures ; Hospitals ; *State Medicine ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Macular Degeneration/drug therapy/epidemiology ; },
abstract = {INTRODUCTION: The neo-vascular age-related macular degeneration (nAmd) is a frequent cause of vision loss, although the intravitreal (Ivt) injections of anti-Vegf (vascular endothelial growth factor) have improved functional outcomes. This study has assessed the healthcare and economic burden on the Italian national health service (Inhs) for patients with nAmd and new users of anti-Vegf.<br><br>METHODS: From the database of Fondazione Ricerca e Salute (ReS), people aged &#x2265;55 and with an in-hospital diagnosis of nAmd and/or an injection of anti-Vegf (aflibercept, ranibizumab, pegaptanib; index date) in 2018 are selected. Those with other conditions treated with anti-Vegf and with an Ivt injection before 2018 are excluded. New users of anti-Vegf are analyzed by sex, age, comorbidities, Ivt administrations, switch of anti-Vegf, local outpatient specialist services (with some focuses) and direct healthcare costs charged to the Inhs Results. In 2018, of 8125 inhabitants aged &#x2265;55 with nAmd (4.6x1000 inhab.; mean age 76&#xb1;9; F: 50%), 1513 (19%) are new users of Ivt anti-Vegf (mean age 74&#xb1;9), whose incidence (0.9x1000) increased with age until 84 years old. A proportion of 60.7% had &#x2265;2 comorbidities (mainly hypertension, dyslipidemia and diabetes). Within the 2nd follow-up year, only 598 patients are still treated (60% were lost). On average, 4.8 Ivt injections in the first and 3.1 in the second year are registered. On average, the total cost charged to the Inhs per new user of anti-Vegf was &#x20ac; 6726 (Ivt anti-Vegf accounted for the 76%) and &#x20ac; 3282 (hospitalizations for causes different from nAmd accounted for the 47%), during the first and the second year, respectively.<br><br>CONCLUSIONS: This analysis suggests that in Italy people with nAmd and new users of anti-Vegf are elderly, affected by many comorbidities, treated with Ivt anti-VEGF less than what is required and authorized to achieve a benefit, undergo very few follow-up outpatient specialist visits and tests and, within the 2nd year, their hospitalizations for causes different from nAmd mainly weighs on the total expenditure charged to the Inhs.},
}
@article {pmid37391574,
year = {2023},
author = {Zhang, SM and Fan, B and Li, YL and Zuo, ZY and Li, GY},
title = {Oxidative Stress-Involved Mitophagy of Retinal Pigment Epithelium and Retinal Degenerative Diseases.},
journal = {Cellular and molecular neurobiology},
volume = {43},
number = {7},
pages = {3265-3276},
pmid = {37391574},
issn = {1573-6830},
support = {82171053//National Natural Science Foundation of China/ ; 20200801043GH//Natural Science Foundation of Jilin Province/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; Reactive Oxygen Species/metabolism ; Mitophagy ; Oxidative Stress/physiology ; *Macular Degeneration ; },
abstract = {The retinal pigment epithelium (RPE) is a highly specialized and polarized epithelial cell layer that plays an important role in sustaining the structural and functional integrity of photoreceptors. However, the death of RPE is a common pathological feature in various retinal diseases, especially in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitophagy, as a programmed self-degradation of dysfunctional mitochondria, is crucial for maintaining cellular homeostasis and cell survival under stress. RPE contains a high density of mitochondria necessary for it to meet energy demands, so severe stimuli can cause mitochondrial dysfunction and the excess generation of intracellular reactive oxygen species (ROS), which can further trigger oxidative stress-involved mitophagy. In this review, we summarize the classical pathways of oxidative stress-involved mitophagy in RPE and investigate its role in the progression of retinal diseases, aiming to provide a new therapeutic strategy for treating retinal degenerative diseases. The role of mitophagy in AMD and DR. In AMD, excessive ROS production promotes mitophagy in the RPE by activating the Nrf2/p62 pathway, while in DR, ROS may suppress mitophagy by the FOXO3-PINK1/parkin signaling pathway or the TXNIP-mitochondria-lysosome-mediated mitophagy.},
}
@article {pmid37391547,
year = {2023},
author = {Ozawa, Y and Ohgami, K and Sasaki, K and Hirano, K and Sunaya, T},
title = {Long-term surveillance provides real-world evidences of safety and effectiveness in intravitreal aflibercept treatment for age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {10597},
pmid = {37391547},
issn = {2045-2322},
mesh = {Humans ; *Drug-Related Side Effects and Adverse Reactions ; *Macular Degeneration/drug therapy ; Prospective Studies ; Receptors, Vascular Endothelial Growth Factor ; Retina ; },
abstract = {This prospective, multicentre, postmarketing surveillance were conducted to report on the long-term safety and effectiveness of intravitreal aflibercept (IVT-AFL) treatment in clinical practice of Japanese patients with neovascular age-related macular degeneration (nAMD) who newly initiated IVT-AFL treatment. The primary outcomes were the incidence of adverse events (AEs) and of adverse drug reactions (ADRs) over 36 months. Number of injections, timing of ADR occurrence, and some effectiveness index were also summarised. A total of 3,872 patients received 7.2 ± 5.8 (mean ± standard deviation) injections, and AEs occurred in 5.73% of patients. ADRs were reported in 2.76% of patients, with ocular and nonocular ADRs in 2.07% and 0.72% of patients, respectively. Most vitreo-retinal events developed within 6 months of initial IVT-AFL treatment, and most instances of increased intraocular pressure and cerebral infarction developed after 6 months of follow-up. Mean best-corrected visual acuity and central retinal thickness were numerically better throughout the follow-up period compared with baseline. These results indicated acceptable tolerability and effectiveness of IVT-AFL treatment in patients with nAMD in clinical practice in Japan. Information regarding the risk and the timing of ADRs is valuable for safe and effective long-term treatment of patients with nAMD.Trial registration number: NCT01756248.},
}
@article {pmid37391516,
year = {2023},
author = {Jones, R and Stratton, IM and Scanlon, PH and Theodoropoulou, S},
title = {Correction to: Disengagement and loss to follow-up in intravitreal injection clinics for neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {37},
number = {15},
pages = {3297},
doi = {10.1038/s41433-023-02589-7},
pmid = {37391516},
issn = {1476-5454},
}
@article {pmid37391182,
year = {2023},
author = {Baur, ID and Labuz, G and Yildirim, TM and Auffarth, GU and Khoramnia, R},
title = {Reversible Multifocality Achieved Through Polypseudophakia.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {240},
number = {8},
pages = {981-988},
doi = {10.1055/a-2079-1692},
pmid = {37391182},
issn = {1439-3999},
mesh = {Humans ; Lens Implantation, Intraocular/methods ; Visual Acuity ; *Phacoemulsification ; *Lenses, Intraocular ; *Lens Capsule, Crystalline ; },
abstract = {Simultaneous implantation of a monofocal or monofocal toric intraocular lens (IOL) into the capsular bag and a multifocal IOL into the ciliary sulcus, referred to as duet procedure, allows us to create multifocality that is more easily reversible than the implantation of a capsular bag-fixated multifocal IOL. The optical quality and results after the duet procedure are equivalent to those of a capsular bag-fixated multifocal IOL. Patients who cannot tolerate the side effects of multifocal optics or who develop an ocular condition leading to loss of function such as age-related macular degeneration (AMD) or glaucoma in the course of their lives may benefit from the reversibility of the procedure.},
}
@article {pmid37388919,
year = {2023},
author = {Orozco, LD and Owen, LA and Hofmann, J and Stockwell, AD and Tao, J and Haller, S and Mukundan, VT and Clarke, C and Lund, J and Sridhar, A and Mayba, O and Barr, JL and Zavala, RA and Graves, EC and Zhang, C and Husami, N and Finley, R and Au, E and Lillvis, JH and Farkas, MH and Shakoor, A and Sherva, R and Kim, IK and Kaminker, JS and Townsend, MJ and Farrer, LA and Yaspan, BL and Chen, HH and DeAngelis, MM},
title = {A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration.},
journal = {Cell genomics},
volume = {3},
number = {6},
pages = {100302},
pmid = {37388919},
issn = {2666-979X},
support = {K08 EY031800/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness, affecting 200 million people worldwide. To identify genes that could be targeted for treatment, we created a molecular atlas at different stages of AMD. Our resource is comprised of RNA sequencing (RNA-seq) and DNA methylation microarrays from bulk macular retinal pigment epithelium (RPE)/choroid of clinically phenotyped normal and AMD donor eyes (n = 85), single-nucleus RNA-seq (164,399 cells), and single-nucleus assay for transposase-accessible chromatin (ATAC)-seq (125,822 cells) from the retina, RPE, and choroid of 6 AMD and 7 control donors. We identified 23 genome-wide significant loci differentially methylated in AMD, over 1,000 differentially expressed genes across different disease stages, and an AMD Müller state distinct from normal or gliosis. Chromatin accessibility peaks in genome-wide association study (GWAS) loci revealed putative causal genes for AMD, including HTRA1 and C6orf223. Our systems biology approach uncovered molecular mechanisms underlying AMD, including regulators of WNT signaling, FRZB and TLE2, as mechanistic players in disease.},
}
@article {pmid37388610,
year = {2023},
author = {Chaudhuri, M and Hassan, Y and Bakka Vemana, PPS and Bellary Pattanashetty, MS and Abdin, ZU and Siddiqui, HF},
title = {Age-Related Macular Degeneration: An Exponentially Emerging Imminent Threat of Visual Impairment and Irreversible Blindness.},
journal = {Cureus},
volume = {15},
number = {5},
pages = {e39624},
pmid = {37388610},
issn = {2168-8184},
abstract = {Age-related macular degeneration (AMD) is a significant cause of blindness globally. With the exponential rise in the aging population, AMD is the third leading cause of visual impairment worldwide. Neovascular AMD (nAMD; Wet AMD) and geographical atrophy (GA, late-stage dry AMD) are the advanced AMD accountable for substantial cases of visual deterioration among the elderly. Our review of the literature depicted that notable risk factors include cigarette smoking, nutritional elements, cardiovascular disorders, and genetic markers, including genes regulating complement, lipid, and angiogenic pathways. Some studies have suggested a relative decline in the proportion of AMD cases in the last two decades attributable to novel diagnostic and therapeutic modalities. Accurate diagnosis is the result of a combination of clinical examination and imaging techniques, including retinal photography, angiography, and optical coherence tomography. The incorporation of dietary antioxidant supplements, explicitly lutein, slows the progression of the disease in advanced stages. The induction of vascular endothelial growth factor (VEGF) inhibitors in the treatment of neovascular AMD, often combined with other modalities, has shown an immensely favorable prognosis. Research to integrate gene therapy and regenerative techniques using stem cells is underway to further mitigate AMD-associated morbidity. It is imperative to establish screening and therapeutic guidelines for AMD to curtail the future social and financial burden and improve the diminishing quality of life among the elderly.},
}
@article {pmid37387192,
year = {2023},
author = {Unterweger, H and Janko, C and Civelek, M and Cicha, I and Spielvogel, H and Tietze, R and Friedrich, B and Alexiou, C},
title = {Nanomaterial-based ophthalmic therapies.},
journal = {Nanomedicine (London, England)},
volume = {18},
number = {10},
pages = {783-788},
doi = {10.2217/nnm-2023-0109},
pmid = {37387192},
issn = {1748-6963},
}
@article {pmid37385535,
year = {2023},
author = {Xiao, R and Lei, C and Zhang, Y and Zhang, M},
title = {Interleukin-6 in retinal diseases: From pathogenesis to therapy.},
journal = {Experimental eye research},
volume = {233},
number = {},
pages = {109556},
doi = {10.1016/j.exer.2023.109556},
pmid = {37385535},
issn = {1096-0007},
mesh = {Humans ; *Diabetic Retinopathy/pathology ; Interleukin-6 ; Retina/pathology ; *Retinal Diseases/drug therapy ; *Retinal Vein Occlusion/drug therapy ; },
abstract = {Interleukin-6 (IL-6) is a pleiotropic cytokine that participates in immunomodulation, inflammation, increases vascular permeability, hematopoiesis, and stimulates cell proliferation, among other biological processes. It exerts effects primarily through the classic and trans-signaling pathways. Many studies have demonstrated that IL-6 plays a critical role in the development of retinal diseases including diabetic retinopathy, uveitis, age-related macular degeneration, glaucoma, retinal vein occlusion, central serous chorioretinopathy and proliferative vitreoretinopathy. Thus, the progressive development of drugs targeting IL-6 and IL-6 receptor may play a role in the treatment of multiple retinal diseases. In this article, we comprehensively review the IL-6's biological functions of and its mechanisms in the pathogenesis of various retinal diseases. Furthermore, we summarize the drugs targeting IL-6 and its receptor and prospect their potential application in retinal diseases, hoping to provide new ideas for the treatment of retinal diseases.},
}
@article {pmid37385300,
year = {2023},
author = {Farnoodian, M and Bose, D and Barone, F and Nelson, LM and Boyle, M and Jun, B and Do, K and Gordon, W and Guerin, MK and Perera, R and Ji, JX and Cogliati, T and Sharma, R and Brooks, BP and Bazan, NG and Bharti, K},
title = {Retina and RPE lipid profile changes linked with ABCA4 associated Stargardt's maculopathy.},
journal = {Pharmacology &amp; therapeutics},
volume = {249},
number = {},
pages = {108482},
pmid = {37385300},
issn = {1879-016X},
support = {ZIA EY000532/ImNIH/Intramural NIH HHS/United States ; R01 EY005121/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Mice ; Animals ; Retinal Pigment Epithelium/metabolism/pathology ; Retina/metabolism ; *Macular Degeneration/genetics/metabolism/pathology ; *Retinal Degeneration ; Lipofuscin/genetics/metabolism ; Atrophy/metabolism/pathology ; ATP-Binding Cassette Transporters/genetics/metabolism ; },
abstract = {Stargardt maculopathy, caused predominantly by mutations in the ABCA4 gene, is characterized by an accumulation of non-degradable visual pigment derivative, lipofuscin, in the retinal pigment epithelium (RPE) - resulting in RPE atrophy. RPE is a monolayer tissue located adjacent to retinal photoreceptors and regulates their health and functioning; RPE atrophy triggers photoreceptor cell death and vision loss in Stargardt patients. Previously, ABCA4 mutations in photoreceptors were thought to be the major contributor to lipid homeostasis defects in the eye. Recently, we demonstrated that ABCA4 loss of function in the RPE leads to cell-autonomous lipid homeostasis defects. Our work underscores that an incomplete understanding of lipid metabolism and lipid-mediated signaling in the retina and RPE are potential causes for lacking treatments for this disease. Here we report altered lipidomic in mouse and human Stargardt models. This work provides the basis for therapeutics that aim to restore lipid homeostasis in the retina and the RPE.},
}
@article {pmid37384534,
year = {2023},
author = {Kang, MJ and Roh, KH and Lee, JS and Lee, JH and Park, S and Lim, DW},
title = {Vascular Endothelial Growth Factor Receptor 1 Targeting Fusion Polypeptides with Stimuli-Responsiveness for Anti-angiogenesis.},
journal = {ACS applied materials &amp; interfaces},
volume = {15},
number = {27},
pages = {32201-32214},
doi = {10.1021/acsami.3c03989},
pmid = {37384534},
issn = {1944-8252},
mesh = {Mice ; Animals ; Humans ; *Vascular Endothelial Growth Factor Receptor-1/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Peptides/pharmacology/chemistry ; Human Umbilical Vein Endothelial Cells/metabolism ; Vascular Endothelial Growth Factors ; *Choroidal Neovascularization ; },
abstract = {Genetically engineered fusion polypeptides have been investigated to introduce unique bio-functionality and improve some therapeutic activity for anti-angiogenesis. We report herein that stimuli-responsive, vascular endothelial growth factor receptor 1 (VEGFR1) targeting fusion polypeptides composed of a VEGFR1 (fms-like tyrosine kinase-1 (Flt1)) antagonist, an anti-Flt1 peptide, and a thermally responsive elastin-based polypeptide (EBP) were rationally designed at the genetic level, biosynthesized, and purified by inverse transition cycling to develop potential anti-angiogenic fusion polypeptides to treat neovascular diseases. A series of hydrophilic EBPs with different block lengths were fused with an anti-Flt1 peptide, forming anti-Flt1-EBPs, and the effect of EBP block length on their physicochemical properties was examined. While the anti-Flt1 peptide decreased phase-transition temperatures of anti-Flt1-EBPs, compared with EBP blocks, anti-Flt1-EBPs were soluble under physiological conditions. The anti-Flt1-EBPs dose dependently inhibited the binding of VEGFR1 against vascular endothelial growth factor (VEGF) as well as tube-like network formation of human umbilical vein endothelial cells under VEGF-triggered angiogenesis in vitro because of the specific binding between anti-Flt1-EBPs and VEGFR1. Furthermore, the anti-Flt1-EBPs suppressed laser-induced choroidal neovascularization in a wet age-related macular degeneration mouse model in vivo. Our results indicate that anti-Flt1-EBPs as VEGFR1-targeting fusion polypeptides have great potential for efficacious anti-angiogenesis to treat retinal-, corneal-, and choroidal neovascularization.},
}
@article {pmid37383167,
year = {2023},
author = {Clemens, CR and Alten, F and Zimmermann, JA and Eter, N},
title = {Old Problem in a New Guise: Retinal Pigment Epithelium Tear after Intravitreal Faricimab (Vabysmo[®]) Injection.},
journal = {Case reports in ophthalmology},
volume = {14},
number = {1},
pages = {241-244},
pmid = {37383167},
issn = {1663-2699},
abstract = {This case report describes a 78-year-old patient who developed a tear of the retinal pigment epithelium (RPE) during faricimab (Vabysmo[®]) therapy. After three consecutive intravitreal aflibercept (Eylea[®]) injections with persistent disease activity, therapy was switched to faricimab. The patient experienced a tear in the RPE 4 weeks postinjection. We report the first published case of RPE tear development after intravitreal faricimab injection in neovascular age-related macular degeneration. Faricimab has a new target structure in the angiopoietin-2 receptor in addition to VEGF. Patients at risk for RPE rupture were excluded from pivotal studies. Further investigation is needed to understand the effect of faricimab not only on visual acuity and intraretinal and subretinal fluid but also on mechanical stress on the RPE monolayer.},
}
@article {pmid37380786,
year = {2024},
author = {Papadopoulos, Z},
title = {The role of the cytokine TNF-α in choroidal neovascularization: a systematic review.},
journal = {Eye (London, England)},
volume = {38},
number = {1},
pages = {25-32},
pmid = {37380786},
issn = {1476-5454},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Tumor Necrosis Factor-alpha ; Cytokines ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Visual Acuity ; *Wet Macular Degeneration/complications ; *Choroidal Neovascularization/drug therapy ; },
abstract = {TNF-α is a multifunctional cytokine produced by macrophages and T cells. This proinflammatory substance is considered to play a crucial role in the inflammatory process associated with age-related macular degeneration (AMD). The current review aimed to describe evidence for an association between TNF-α and AMD reported in various studies. The MEDLINE, Embase, PubMed and Global Health databases were systematically searched to identify studies that investigated the role of TNF-α in AMD. A total of 24 studies were deemed eligible for the review. To better understand and integrate the evidence, the studies were categorised into four major groups in relation to the role of TNF-α in AMD: (1) those examining biological signalling pathways through which TNF-α exerts its effect; (2) investigating levels of TNF-α; (3) exploring the genetics underlying the role of TNF-α; and (4) assessing anti-TNF-α agents as potential treatments for AMD. TNF-α is thought to directly contribute to choroidal neovascularization (CNV) enhancement and has been shown to exert its effect by augmenting the inflammatory response through other signalling pathways. Additionally, different genes have been found to be associated with activities linked to TNF-α in AMD. Overall, measurement of systemic and local levels of TNF-α has not yielded consistent findings, with variable conclusions for the role of anti-TNF-α agents in remission of AMD symptoms. The role of TNF-α in neovascular AMD is not clear, and not all anti-TNF-α agents are safe. The potential of this cytokine in atrophic AMD has not been examined. Future studies should address these unresolved questions.},
}
@article {pmid37377777,
year = {2023},
author = {Canonica, J and Foxton, R and Garrido, MG and Lin, CM and Uhles, S and Shanmugam, S and Antonetti, DA and Abcouwer, SF and Westenskow, PD},
title = {Delineating effects of angiopoietin-2 inhibition on vascular permeability and inflammation in models of retinal neovascularization and ischemia/reperfusion.},
journal = {Frontiers in cellular neuroscience},
volume = {17},
number = {},
pages = {1192464},
pmid = {37377777},
issn = {1662-5102},
support = {R01 EY012021/EY/NEI NIH HHS/United States ; R01 EY029349/EY/NEI NIH HHS/United States ; R01 HL055374/HL/NHLBI NIH HHS/United States ; },
abstract = {INTRODUCTION: Clinical trials demonstrated that co-targeting angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF-A) with faricimab controls anatomic outcomes and maintains vision improvements, with strong durability, through 2 years in patients with neovascular age-related macular degeneration and diabetic macular edema. The mechanism(s) underlying these findings is incompletely understood and the specific role that Ang-2 inhibition plays requires further investigation.<br><br>METHODS: We examined the effects of single and dual Ang-2/VEGF-A inhibition in diseased vasculatures of JR5558 mice with spontaneous choroidal neovascularization (CNV) and in mice with retinal ischemia/reperfusion (I/R) injuries.<br><br>RESULTS: In JR5558 mice, Ang-2, VEGF-A, and dual Ang-2/VEGF-A inhibition reduced CNV area after 1 week; only dual Ang-2/VEGF-A inhibition decreased neovascular leakage. Only Ang-2 and dual Ang-2/VEGF-A inhibition maintained reductions after 5 weeks. Dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 1 week. Both Ang-2 and dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 5 weeks. In the retinal I/R injury model, dual Ang-2/VEGF-A inhibition was statistically significantly more effective than Ang-2 or VEGF-A inhibition alone in preventing retinal vascular leakage and neurodegeneration.<br><br>DISCUSSION: These data highlight the role of Ang-2 in dual Ang-2/VEGF-A inhibition and indicate that dual inhibition has complementary anti-inflammatory and neuroprotective effects, suggesting a mechanism for the durability and efficacy of faricimab in clinical trials.},
}
@article {pmid37374314,
year = {2023},
author = {Gesualdo, C and Rossi, S and Iodice, CM and Guarino, F and Petrella, M and D'Agostino, FA and Perrotta, R and Simonelli, F},
title = {Brolucizumab Intravitreal Injections for Wet Age-Related Macular Degeneration: Real-Life Study on a Cohort of Italian Patients.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {6},
pages = {},
pmid = {37374314},
issn = {1648-9144},
support = {PRIN 2020FR7TCL_002//ITALIAN MINISTRY OF EDUCATION, UNIVERSITY AND RESEARCH/ ; },
mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; *Tomography, Optical Coherence ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; },
abstract = {Background and Objectives: To report the real-life Brolucizumab therapeutical outcomes of treatment-naïve and non-treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) and to analyze the incidence of therapy-related adverse events. Materials and Methods: A total of 56 eyes of 54 patients diagnosed with nAMD were retrospectively evaluated over a 3-month follow-up. Naïve eyes received a 3-month loading phase, whereas non-naïve eyes were treated with one intravitreal injection + ProReNata scheme. The main outcome measures were best-corrected visual acuity (BCVA) and central retinal thickness (CRT) change. In addition, patients were stratified on the basis of fluid accumulation site, whether intra-retinal (IRF), sub-retinal (SRF), or sub-retinal pigmented epithelium (SRPE), to separately assess the eventual BCVA change in each subgroup. Finally, the incidence of ocular adverse events was evaluated. Results: In naïve eyes, a significant improvement of BCVA (LogMar) was observed at all timepoints from baseline (1 month-Mean Difference (MD): -0.13; 2 months MD: -0.17; 3 months MD: -0.24). In non-naïve eyes, a significant mean change was observed at all timepoints, with the exception of 1-month follow-up (2 months MD: -0.08; 3 months MD: -0.05). CRT significantly changed in both groups at all timepoints at a similar pace within the first two months, with naïve eyes displaying a larger overall thickness decrease at the end of the follow-up (Group 1 = MD: -123.91 µm; Group 2 = MD: -110.33 µm). With respect to the location of the edema, a significant BCVA change was observed in naïve patients with fluid in all three sites at the end of the follow-up (SRPE = MD: -0.13 (p = 0.043); SR = MD: -0.15 (p = 0.019); IR = MD: -0.19 (p = 0.041). Non-naïve patients exhibited significant mean BCVA changes only with respect to SR and IR fluid presence (SRPE = MD: -0.13 (p = 0.152); SR = MD: -0.15 (p = 0.007); IR = MD: -0.06 (p = 0.011). One naïve patient experienced acute-onset anterior and intermediate uveitis which completely resolved after therapy. Conclusions: Brolucizumab was demonstrated to be a safe and efficient alternative in improving both the anatomical and functional parameters of eyes with nAMD in this small, uncontrolled, series of patients.},
}
@article {pmid37373576,
year = {2023},
author = {Schuster, AK and Wolfram, C and Hudde, T and Klatt, A and Schnegelsberg, B and Midani-Oezkan, H and Ross, M and Ziemssen, F and Pfeiffer, N},
title = {Impact of Routinely Performed Optical Coherence Tomography Examinations on Quality of Life in Patients with Retinal Diseases-Results from the ALBATROS Data Collection.},
journal = {Journal of clinical medicine},
volume = {12},
number = {12},
pages = {},
pmid = {37373576},
issn = {2077-0383},
support = {Not able to provide at the moment//Novartis (Germany)/ ; },
abstract = {UNLABELLED: The use of OCT to monitor intravitreal treatment varies in clinical practice and is not always mandatory. The ALBATROS data collection aimed to clarify the impact of routinely implemented OCT on clinical outcomes and its impact on vision-related quality of life (VRQoL).<br><br>METHODS: An observational cohort study included patients with retinal diseases starting an intravitreal anti-vascular endothelial growth factor treatment in Germany. Treatment followed clinical practice except mandatory OCT examination during the 12-month observation period. VRQoL was assessed by NEI VFQ-25 and compared with respect to OCT examinations and number of intravitreal injections in the different diseases (nAMD, DME, BRVO, CRVO).<br><br>RESULTS: 1478 patients (74.5 &#xb1; 10.9 years, 54.9% female) were included in the analysis. Patients had neovascular AMD (65.2%), DME (18.4%), BRVO (9.5%), or CRVO (6.9%). 8.8 &#xb1; 2.6 OCT examinations and 6.1 &#xb1; 3.2 intravitreal injections were performed within 12 months. VRQoL differed between indications at baseline, with substantially lower values for neovascular AMD and CRVO. After twelve months, an increase in visual acuity and visual functional scale was observed for nAMD, DME, and BRVO, while in DME only, there was an association between number of OCT examinations and VRQoL.<br><br>CONCLUSION: Intravitreal treatment was able to maintain VRQoL over twelve months in a real-world setting. Regular OCT examinations were associated with higher gain in VRQoL in DME patients after 12 months.},
}
@article {pmid37373474,
year = {2023},
author = {Künzel, SE and Flesch, LTM and Frentzel, DP and Knecht, VA and Rübsam, A and Dreher, F and Schütte, M and Dubrac, A and Lange, B and Yaspo, ML and Lehrach, H and Joussen, AM and Zeitz, O},
title = {Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {24},
number = {12},
pages = {},
pmid = {37373474},
issn = {1422-0067},
support = {N/A//Novartis (Germany)/ ; },
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; Proteome ; Prospective Studies ; Chromatography, Liquid ; Cross-Sectional Studies ; Proteomics ; Tandem Mass Spectrometry ; *Macular Degeneration/drug therapy ; Phenotype ; },
abstract = {There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient's level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD.},
}
@article {pmid37373423,
year = {2023},
author = {Wang, H and Ramshekar, A and Cung, T and Wallace-Carrete, C and Zaugg, C and Nguyen, J and Stoddard, GJ and Hartnett, ME},
title = {7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence and Fibrosis of Choroidal Neovascularization via IQGAP1 Phosphorylation-Dependent Signaling.},
journal = {International journal of molecular sciences},
volume = {24},
number = {12},
pages = {},
pmid = {37373423},
issn = {1422-0067},
support = {R01 EY015130/EY/NEI NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; R01 EY017011/EY/NEI NIH HHS/United States ; F30 EY032311/EY/NEI NIH HHS/United States ; EY015130, EY017011 and F30EY032311/NH/NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; Cellular Senescence ; *Choroidal Neovascularization/pathology ; Fibrosis ; *Macular Degeneration/metabolism ; Mammals/metabolism ; Phosphorylation ; Retinal Pigment Epithelium/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism ; ras GTPase-Activating Proteins/metabolism ; },
abstract = {Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells also developed senescence-associated secretory phenotype (SASP) determined by increased IL-1β, IL-6, and VEGF through mTOR-mediated NF-κB signaling, and reduced barrier integrity that was restored by the mTOR inhibitor, rapamycin. 7KC-induced p21, VEGF, and IL-1β were inhibited by an inhibitor of protein kinase C. The kinase regulates IQGAP1 serine phosphorylation. Furthermore, after 7KC injection and laser-induced injury, mice with an IQGAP1 serine 1441-point mutation had significantly reduced fibrosis compared to littermate control mice. Our results provide evidence that age-related accumulation of 7KC in drusen mediates senescence and SASP in RPE, and IQGAP1 serine phosphorylation is important in causing fibrosis in AMD.},
}
@article {pmid37372373,
year = {2023},
author = {Kirkby, J and Halford, S and Shanks, M and Moore, A and Gait, A and Jenkins, L and Clouston, P and Patel, CK and Downes, SM},
title = {A Carrier Female Manifesting an Unusual X-Linked Retinoschisis Phenotype Associated with the Pathogenic Variant c.266delA, p.(Tyr89LeufsTer37) in RS1, and Skewed X-Inactivation.},
journal = {Genes},
volume = {14},
number = {6},
pages = {},
pmid = {37372373},
issn = {2073-4425},
mesh = {Female ; Humans ; Eye Proteins/genetics ; Phenotype ; Retina/pathology ; *Retinoschisis/genetics/pathology ; X Chromosome Inactivation/genetics ; Child, Preschool ; },
abstract = {X-linked retinoschisis (XLRS) is the most common juvenile macular degeneration in males. Unlike most other X-linked retinal dystrophies, carrier heterozygous females are very rarely reported to show clinical features of the disease. Herein, we describe unusual retinal features in a 2-year-old female infant with family history and genetic testing consistent with XLRS.},
}
@article {pmid37372009,
year = {2023},
author = {Toppila, M and Hytti, M and Korhonen, E and Ranta-Aho, S and Harju, N and Forsberg, MM and Kaarniranta, K and Jalkanen, A and Kauppinen, A},
title = {The Prolyl Oligopeptidase Inhibitor KYP-2047 Is Cytoprotective and Anti-Inflammatory in Human Retinal Pigment Epithelial Cells with Defective Proteasomal Clearance.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {6},
pages = {},
pmid = {37372009},
issn = {2076-3921},
support = {3-years project funding//The Emil Aaltonen Foundation/ ; 297267, 307341, 328443//The Academy of Finland/ ; },
abstract = {Increased oxidative stress, dysfunctional cellular clearance, and chronic inflammation are associated with age-related macular degeneration (AMD). Prolyl oligopeptidase (PREP) is a serine protease that has numerous cellular functions, including the regulation of oxidative stress, protein aggregation, and inflammation. PREP inhibition by KYP-2047 (4-phenylbutanoyl-L-prolyl1(S)-cyanopyrrolidine) has been associated with clearance of cellular protein aggregates and reduced oxidative stress and inflammation. Here, we studied the effects of KYP-2047 on inflammation, oxidative stress, cell viability, and autophagy in human retinal pigment epithelium (RPE) cells with reduced proteasomal clearance. MG-132-mediated proteasomal inhibition in ARPE-19 cells was used to model declined proteasomal clearance in the RPEs of AMD patients. Cell viability was assessed using LDH and MTT assays. The amounts of reactive oxygen species (ROS) were measured using 2',7'-dichlorofluorescin diacetate (H2DCFDA). ELISA was used to determine the levels of cytokines and activated mitogen-activated protein kinases. The autophagy markers p62/SQSTM1 and LC3 were measured with the western blot method. MG-132 induced LDH leakage and increased ROS production in the ARPE-19 cells, and KYP-2047 reduced MG-132-induced LDH leakage. Production of the proinflammatory cytokine IL-6 was concurrently alleviated by KYP-2047 when compared with cells treated only with MG-132. KYP-2047 had no effect on autophagy in the RPE cells, but the phosphorylation levels of p38 and ERK1/2 were elevated upon KYP-2047 exposure, and the inhibition of p38 prevented the anti-inflammatory actions of KYP-2047. KYP-2047 showed cytoprotective and anti-inflammatory effects on RPE cells suffering from MG-132-induced proteasomal inhibition.},
}
@article {pmid37371981,
year = {2023},
author = {Jamrozik, D and Dutczak, R and Machowicz, J and Wojtyniak, A and Smędowski, A and Pietrucha-Dutczak, M},
title = {Metallothioneins, a Part of the Retinal Endogenous Protective System in Various Ocular Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {6},
pages = {},
pmid = {37371981},
issn = {2076-3921},
support = {PCN-1-135/N/2/O//Medical University of Silesia/ ; },
abstract = {Metallothioneins are the metal-rich proteins that play important roles in metal homeostasis and detoxification. Moreover, these proteins protect cells against oxidative stress, inhibit proapoptotic mechanisms and enhance cell differentiation and survival. Furthermore, MTs, mainly MT-1/2 and MT-3, play a vital role in protecting the neuronal retinal cells in the eye. Expression disorders of these proteins may be responsible for the development of various age-related eye diseases, including glaucoma, age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa. In this review, we focused on the literature reports suggesting that these proteins may be a key component of the endogenous protection system of the retinal neurons, and, when the expression of MTs is disrupted, this system becomes inefficient. Moreover, we described the location of different MT isoforms in ocular tissues. Then we discussed the changes in MT subtypes' expression in the context of the common eye diseases. Finally, we highlighted the possibility of the use of MTs as biomarkers for cancer diagnosis.},
}
@article {pmid37371942,
year = {2023},
author = {Kropp, M and Mohit, M and Leroy-Ciocanea, CI and Schwerm, L and Harmening, N and Bascuas, T and De Clerck, E and Kreis, AJ and Pajic, B and Johnen, S and Thumann, G},
title = {Mammalian Animal and Human Retinal Organ Culture as Pre-Clinical Model to Evaluate Oxidative Stress and Antioxidant Intraocular Therapeutics.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {6},
pages = {},
pmid = {37371942},
issn = {2076-3921},
support = {189341/SNSF_/Swiss National Science Foundation/Switzerland ; },
abstract = {Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in terms of transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed the model's quality, induced OS, and tested the efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by a high amount of glucose or hydrogen peroxide (H2O2) and treated with scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage colony-stimulating factor (GM-CSF). The tissue morphology, cell viability, inflammation, and glutathione level were determined. The retina samples showed only moderate necrosis (23.83 ± 5.05 increased to 27.00 ± 1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3 ± 59.9 vs. 435.7 ± 166.8 nM ATP in the controls) and the antioxidants reduced OS-induced apoptosis (from 124.20 ± 51.09 to 60.80 ± 319.66 cells/image after the scutellarin treatment). Enhanced mammalian animal and human retina cultures enable reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.},
}
@article {pmid37371913,
year = {2023},
author = {Pinelli, R and Ferrucci, M and Biagioni, F and Berti, C and Bumah, VV and Busceti, CL and Puglisi-Allegra, S and Lazzeri, G and Frati, A and Fornai, F},
title = {Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {6},
pages = {},
pmid = {37371913},
issn = {2076-3921},
support = {Ricerca Corrente 2023//Ministero della Salute/ ; },
abstract = {The seminal role of autophagy during age-related macular degeneration (AMD) lies in the clearance of a number of reactive oxidative species that generate dysfunctional mitochondria. In fact, reactive oxygen species (ROS) in the retina generate misfolded proteins, alter lipids and sugars composition, disrupt DNA integrity, damage cell organelles and produce retinal inclusions while causing AMD. This explains why autophagy in the retinal pigment epithelium (RPE), mostly at the macular level, is essential in AMD and even in baseline conditions to provide a powerful and fast replacement of oxidized molecules and ROS-damaged mitochondria. When autophagy is impaired within RPE, the deleterious effects of ROS, which are produced in excess also during baseline conditions, are no longer counteracted, and retinal degeneration may occur. Within RPE, autophagy can be induced by various stimuli, such as light and naturally occurring phytochemicals. Light and phytochemicals, in turn, may synergize to enhance autophagy. This may explain the beneficial effects of light pulses combined with phytochemicals both in improving retinal structure and visual acuity. The ability of light to activate some phytochemicals may further extend such a synergism during retinal degeneration. In this way, photosensitive natural compounds may produce light-dependent beneficial antioxidant effects in AMD.},
}
@article {pmid37371657,
year = {2023},
author = {Vofo, BN and Chowers, I},
title = {Suppressing Inflammation for the Treatment of Diabetic Retinopathy and Age-Related Macular Degeneration: Dazdotuftide as a Potential New Multitarget Therapeutic Candidate.},
journal = {Biomedicines},
volume = {11},
number = {6},
pages = {},
pmid = {37371657},
issn = {2227-9059},
abstract = {Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are major causes of blindness globally. The primary treatment option for DME and neovascular AMD (nAMD) is anti-vascular endothelial growth factor (VEGF) compounds, but this treatment modality often yields insufficient results, and monthly injections can place a burden on the health system and patients. Although various inflammatory pathways and mediators have been recognized as key players in the development of DR and AMD, there are limited treatment options targeting these pathways. Molecular pathways that are interlinked, or triggers of multiple inflammatory pathways, could be promising targets for drug development. This review focuses on the role of inflammation in the pathogenesis of DME and AMD and presents current anti-inflammatory compounds, as well as a potential multitarget anti-inflammatory compound (dazdotuftide) that could be a candidate treatment option for the management of DME and AMD.},
}
@article {pmid37371644,
year = {2023},
author = {Biarnés, M and Garrell-Salat, X and Gómez-Benlloch, A and Guarro, M and Londoño, G and López, E and Ruiz, S and Vázquez, M and Sararols, L},
title = {Methodological Appraisal of Phase 3 Clinical Trials in Geographic Atrophy.},
journal = {Biomedicines},
volume = {11},
number = {6},
pages = {},
pmid = {37371644},
issn = {2227-9059},
abstract = {Geographic atrophy (GA) secondary to age-related macular degeneration is a common cause of blindness worldwide. Given the recent approval of the first therapy for GA, pegcetacoplan, we critically appraise methodological aspects of the phase 3 clinical trials published so far in this disease in relation to their design, analysis and interpretation. We reviewed some of the key attributes of all phase 3 clinical trials in GA available in the main public registry of clinical trials as of 20 May 2023. The topics discussed included types of endpoints, eligibility criteria, p-value and effect size, study power and sample size, the intention to treat principle, missing data, consistency of results, efficacy-safety balance and application of results. Five phase 3 clinical trials have reported results, either partially or completely: GATHER1, DERBY/OAKS, CHROMA/SPECTRI, SEATTLE and GATE. Although there are many similarities between these trials in terms of endpoints or broad eligibility criteria, they differ in several aspects (metric of the primary endpoint, sample size, type of adverse events, etc.) that can influence the results, which are discussed. Readers should understand key methodological aspects of clinical trials to improve their interpretation. On the other hand, authors should adhere to clinical trial reporting guidelines to communicate what was done and how it was done.},
}
@article {pmid37371603,
year = {2023},
author = {Chen, CH and Lin, HC and Lin, HL and Keller, JJ and Wang, LH},
title = {Association between Antihyperlipidemic Agent Use and Age-Related Macular Degeneration in Patients with Hyperlipidemia: A Population-Based Retrospective Cohort Study.},
journal = {Biomedicines},
volume = {11},
number = {6},
pages = {},
pmid = {37371603},
issn = {2227-9059},
support = {111TMUH-MOST-07//Taipei Medical University Hospital/ ; },
abstract = {Several studies have indicated that lipoproteins might contribute to the pathogenesis of age-related macular degeneration (AMD). In this population-based retrospective cohort study, patients with hyperlipidemia were divided into two groups (study groups I and II) based on whether or not they were receiving antihyperlipidemic agents. The comparison group included patients without hyperlipidemia who were randomly selected and matched with study group II patients. A Cox proportional hazard model was used to evaluate the risk of AMD among the groups. Patients with hyperlipidemia receiving antihyperlipidemic agents (study group I, n = 15,482) had a significantly increased AMD risk (adjusted hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.04-1.45) compared to those not receiving antihyperlipidemic agents (study group II, n = 15,482). However, with an increase in cumulative exposure, a reduced risk of AMD was observed in patients using a defined daily dose of more than 721, with an adjusted HR of 0.34 (95% CI = 0.22-0.53, p < 0.001). Additionally, the adjusted HR of AMD for study group II was 1.40 (95% CI = 1.20-1.63, p < 0.001) relative to the comparison group (n = 61,928). In conclusion, the study results indicated that patients with hyperlipidemia have a higher AMD risk than patients without hyperlipidemia. Furthermore, patients with hyperlipidemia who received antihyperlipidemic agents had a significantly increased AMD risk. However, a dose-dependent reduction in the risk of AMD was observed in patients with hyperlipidemia using statins or/and fibrates.},
}
@article {pmid37371562,
year = {2023},
author = {Choubey, M and Bora, P},
title = {Emerging Role of Adiponectin/AdipoRs Signaling in Choroidal Neovascularization, Age-Related Macular Degeneration, and Diabetic Retinopathy.},
journal = {Biomolecules},
volume = {13},
number = {6},
pages = {},
pmid = {37371562},
issn = {2218-273X},
mesh = {Animals ; Humans ; Mice ; *Adiponectin/genetics/metabolism ; Angiogenesis Inhibitors/therapeutic use ; *Choroidal Neovascularization/genetics/metabolism ; Diabetes Mellitus ; *Diabetic Retinopathy/genetics/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Visual Acuity ; *Wet Macular Degeneration/genetics/metabolism ; Receptors, Adiponectin/genetics/metabolism ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of irreversible blindness in adults, may result in poor central vision, making it difficult to see, read, and drive. AMD is generally classified in either dry or wet types. Milder cases of dry AMD may progress to geographic atrophy (GA), leading to significant visual disability; wet, or neovascular AMD, which involves choroidal neovascularization (CNV), can lead to complete loss of central vision. Adiponectin (APN) discovery in the mid-1990's and, subsequently, its two cognate receptors (AdipoRs) in the early 2000s have led to a remarkable progress in better understanding metabolic disorders, as well as metabolism-associated ocular pathology. APN/AdipoRs signaling plays a central role in a variety of molecular and cellular physiological events, including glucose and lipid metabolism, whole-body energy regulation, immune and inflammation responses, insulin sensitivity and retinal cell biological functions. This review is an amalgamation of recent information related to APN/AdipoRs in the pathophysiology of retinal diseases and furthers its association with AMD and diabetic retinopathy. Additionally, we present our original research, where we designed control peptide and CNV inhibitory peptide from the globular region of APN to see the effect of these peptides on the mouse model of laser-induced CNV. The inhibitory peptide (APN1) inhibited CNV by more than 75% while the control peptide did not inhibit CNV.},
}
@article {pmid37371481,
year = {2023},
author = {Si, Z and Zheng, Y and Zhao, J},
title = {The Role of Retinal Pigment Epithelial Cells in Age-Related Macular Degeneration: Phagocytosis and Autophagy.},
journal = {Biomolecules},
volume = {13},
number = {6},
pages = {},
pmid = {37371481},
issn = {2218-273X},
mesh = {Aged ; Humans ; *Phagocytosis/physiology ; Autophagy/physiology ; *Macular Degeneration/metabolism ; Oxidative Stress ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Age-related macular degeneration (AMD) causes vision loss in the elderly population. Dry AMD leads to the formation of Drusen, while wet AMD is characterized by cell proliferation and choroidal angiogenesis. The retinal pigment epithelium (RPE) plays a key role in AMD pathogenesis. In particular, helioreceptor renewal depends on outer segment phagocytosis of RPE cells, while RPE autophagy can protect cells from oxidative stress damage. However, when the oxidative stress burden is too high and homeostasis is disturbed, the phagocytosis and autophagy functions of RPE become damaged, leading to AMD development and progression. Hence, characterizing the roles of RPE cell phagocytosis and autophagy in the pathogenesis of AMD can inform the development of potential therapeutic targets to prevent irreversible RPE and photoreceptor cell death, thus protecting against AMD.},
}
@article {pmid37371114,
year = {2023},
author = {Jang, HY and Cho, CS and Shin, YM and Kwak, J and Sung, YH and Kang, BC and Kim, JH},
title = {Isolation and Characterization of the Primary Marmoset (Callithrix jacchus) Retinal Pigment Epithelial Cells.},
journal = {Cells},
volume = {12},
number = {12},
pages = {},
pmid = {37371114},
issn = {2073-4409},
mesh = {Animals ; Humans ; *Callithrix ; Retinal Pigment Epithelium/metabolism ; Cells, Cultured ; *Macular Degeneration/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Marmosets have emerged as a valuable primate model in ophthalmic research due to their similarity to the human visual system and their potential for generating transgenic models to advance the development of therapies. In this study, we isolated and cultured primary retinal pigment epithelium (RPE) cells from marmosets to investigate the mechanisms underlying RPE dysfunction in aging and age-related macular degeneration (AMD). We confirmed that our culture conditions and materials supported the formation of RPE monolayers with functional tight junctions that closely resembled the in vivo RPE. Since serum has been shown to induce epithelial-mesenchymal transition (EMT) in RPE cells, we compared the effects of fetal bovine serum (FBS) with serum-free supplements B27 on transepithelial electrical resistance (TER), cell proliferation, and morphological characteristics. Additionally, we assessed the age-related morphological changes of in vivo and primary RPE cells. Our results indicate that primary marmoset RPE cells exhibit in vivo-like characteristics, while cells obtained from an older donor show evidence of aging, including a failure to form a polarized monolayer, low TER, and delayed cell cycle. In conclusion, our primary marmoset RPE cells provide a reliable in vitro model for developing novel therapeutics for visual-threatening disorders such as AMD, which can be used before animal experiments using marmosets.},
}
@article {pmid37370889,
year = {2023},
author = {Darooei, R and Nazari, M and Kafieh, R and Rabbani, H},
title = {Optimal Deep Learning Architecture for Automated Segmentation of Cysts in OCT Images Using X-Let Transforms.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
pmid = {37370889},
issn = {2075-4418},
abstract = {The retina is a thin, light-sensitive membrane with a multilayered structure found in the back of the eyeball. There are many types of retinal disorders. The two most prevalent retinal illnesses are Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME). Optical Coherence Tomography (OCT) is a vital retinal imaging technology. X-lets (such as curvelet, DTCWT, contourlet, etc.) have several benefits in image processing and analysis. They can capture both local and non-local features of an image simultaneously. The aim of this paper is to propose an optimal deep learning architecture based on sparse basis functions for the automated segmentation of cystic areas in OCT images. Different X-let transforms were used to produce different network inputs, including curvelet, Dual-Tree Complex Wavelet Transform (DTCWT), circlet, and contourlet. Additionally, three different combinations of these transforms are suggested to achieve more accurate segmentation results. Various metrics, including Dice coefficient, sensitivity, false positive ratio, Jaccard index, and qualitative results, were evaluated to find the optimal networks and combinations of the X-let's sub-bands. The proposed network was tested on both original and noisy datasets. The results show the following facts: (1) contourlet achieves the optimal results between different combinations; (2) the five-channel decomposition using high-pass sub-bands of contourlet transform achieves the best performance; and (3) the five-channel decomposition using high-pass sub-bands formations out-performs the state-of-the-art methods, especially in the noisy dataset. The proposed method has the potential to improve the accuracy and speed of the segmentation process in clinical settings, facilitating the diagnosis and treatment of retinal diseases.},
}
@article {pmid37369771,
year = {2023},
author = {Shen, Y and Xu, M and Ren, L and Li, X and Han, X and Cao, X and Yao, J and Yan, B},
title = {A novel retinoic acid drug, EYE-502, inhibits choroidal neovascularization by targeting endothelial cells and pericytes.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {10439},
pmid = {37369771},
issn = {2045-2322},
mesh = {Humans ; *Pericytes/metabolism ; Endothelial Cells/metabolism ; Pharmaceutical Preparations ; Tretinoin/pharmacology/therapeutic use ; Phosphatidylinositol 3-Kinases ; *Choroidal Neovascularization/drug therapy/metabolism ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; Platelet-Derived Growth Factor/pharmacology ; Intravitreal Injections ; },
abstract = {Choroidal neovascularization (CNV) occurs in neovascular age-related macular degeneration (AMD) and often leads to permanent visual impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the gold standard for the treatment of CNV. However, anti-VEGF treatment did not always cause vision improvement and sometimes had detrimental effects on normal retinal tissues. Herein, we identified a novel retinoic acid drug, EYE-502, which had great therapeutic effects on CNV. Administration of EYE-502 could inhibit VEGF-induced dysfunction of endothelial cells (ECs) and reduce platelet-derived growth factor (PDGF)-induced recruitment of pericytes to ECs in vitro. Administration of EYE-502 could reduce the area of choroidal sprouting and laser-induced CNV, exhibiting similar anti-angiogenic effects as aflibercept. Moreover, administration of EYE-502 could reduce pericyte coverage in the sprouting vessels and choroidal neovascularization. Mechanistically, EYE-502 primarily bound to retinoic acid receptors (RARs) and exerted the anti-angiogenic effects by targeting ECs and pericytes via affecting the activation of Wnt/β-catenin and PDGF/PDGFR/PI3K/Akt signaling. Taken together, this study reports a novel retinoic acid drug, EYE-502, which can exert the anti-angiogenic effects by simultaneous targeting of ECs and pericytes.},
}
@article {pmid37369498,
year = {2023},
author = {Gourgouli, DM and Gourgouli, I and Spai, S and Gourgouli, K and Tzorovili, E and Skouroliakou, M and Papakonstantinou, D and Moschos, MM},
title = {Effect of the Mediterranean Diet on Progression of Dry Form of Age-related Macular Degeneration.},
journal = {In vivo (Athens, Greece)},
volume = {37},
number = {4},
pages = {1809-1815},
pmid = {37369498},
issn = {1791-7549},
mesh = {Humans ; Male ; Female ; Aged ; Aged, 80 and over ; *Diet, Mediterranean ; *Macular Degeneration/diagnosis/diet therapy ; *Dietary Supplements ; Tomography, Optical Coherence ; Visual Acuity ; Disease Progression ; },
abstract = {BACKGROUND/AIM: The aim of this study was to investigate the possible effect of the Mediterranean diet (Med Diet) on the progression of age-related macular degeneration (AMD) in patients with early or intermediate stages of dry AMD.<br><br>PATIENTS AND METHODS: The present study included 164 patients with early or intermediate dry AMD. Data collected included demographics, anthropometric data, ophthalmic and medical history. AMD progression was evaluated using patients' optical coherence tomography (OCT) and visual acuity. Using the MedDietScore, sample's attachment to Med Diet was evaluated, and distinguished into high and low. The association of supplement intake and adherence to Med Diet with AMD progression was investigated using logistic regression.<br><br>RESULTS: Sample's mean age was 73&#xb1;7.4 years. A positive correlation was found between dietary supplementation and slowing of AMD progression, as well as between high adherence to Med Diet and slowing of AMD progression. In contrast, smokers had 51.4% higher risk of AMD progression (p=0.043). The rate of slowing AMD progression was higher in patients who followed Med Diet and received a dietary supplement, compared to patients who followed one or none of the aforementioned recommendations (p<0.001).<br><br>CONCLUSION: Adherence to the Med Diet could have a positive effect on delaying AMD progression in advanced stages, both in patients receiving or not antioxidants. Therefore, our study proposes to strengthen recommendations to AMD patients to follow a Med Diet.},
}
@article {pmid37367859,
year = {2023},
author = {Thee, EF and Acar, &#x130;E and Colijn, JM and Meester-Smoor, MA and Verzijden, T and Baart, SJ and Jarboui, MA and Fauser, S and Hoyng, CB and Ueffing, M and den Hollander, AI and Klaver, CCW and , },
title = {Systemic Metabolomics in a Framework of Genetics and Lifestyle in Age-Related Macular Degeneration.},
journal = {Metabolites},
volume = {13},
number = {6},
pages = {},
pmid = {37367859},
issn = {2218-1989},
support = {Horizon 2020 grant no.: 634479//European Union/ ; //Erasmus MC/ ; //Erasmus University Rotterdam/ ; //the Research Institute for Diseases in the Elderly/ ; //the Ministry of Health, Welfare and Sports/ ; //the Ministry of Education, Culture and Science/ ; //the European Commission/ ; //the Municipality of Rotterdam/ ; nos.: 175.010.2005.011 and 911-03-012//Netherlands Organisation of Scientific Research/ ; grant no.: 014-93-015 [RIDE2]//the Research Institute for Diseases in the Elderly/ ; grant no.: 050-060-810//the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research and Netherlands Consortium for Healthy Aging/ ; 2015-36//Uitzicht/ ; //Oogfonds/ ; //MaculaFonds/ ; //Landelijkse Stichting voor Blinden en Slechtzienden/ ; 2018-34//Uitzicht/ ; Ammodo Award to C.C.W. Klaver//Royal Dutch Academy of Sciences/ ; //Novartis Fonds/ ; //Stichting Blindenhulp/ ; //Stichting A.F. Deutman Oogheelkunde Researchfonds/ ; Vidi Innovational Research Award 016.096.309//the Netherlands Organization for Scientific Research/ ; FP/2007-2013//the European Research Council under the European Union's Seventh Framework Programme/ ; 016.Vici.170.024 to AIdH//the Dutch Organization for Scientific Research/ ; },
abstract = {Insights into the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness, point towards a complex interplay of genetic and lifestyle factors triggering various systemic pathways. This study aimed to characterize metabolomic profiles for AMD and to evaluate their position in the trias with genetics and lifestyle. This study included 5923 individuals from five European studies. Blood metabolomics were assessed using a nuclear magnetic resonance platform of 146 metabolites. Associations were studied using regression analyses. A genetic risk score (GRS) was calculated using β-values of 49 AMD variants, a lifestyle risk score (LRS) using smoking and diet data, and a metabolite risk score (MRS) using metabolite values. We identified 61 metabolites associated with early-intermediate AMD, of which 94% were lipid-related, with higher levels of HDL-subparticles and apolipoprotein-A1, and lower levels of VLDL-subparticles, triglycerides, and fatty acids (false discovery rate (FDR) p-value < 1.4 × 10[-2]). Late AMD was associated with lower levels of the amino acids histidine, leucine, valine, tyrosine, and phenylalanine, and higher levels of the ketone bodies acetoacetate and 3-hydroxybutyrate (FDR p-value < 1.5 × 10[-3]). A favorable lifestyle characterized by a healthy diet was associated with higher levels of amino acids and lower levels of ketone bodies, while an unfavorable lifestyle, including smoking, showed opposite effects (FDR p-value < 2.7 × 10[-2]). The MRS mediated 5% of the effect of the GRS and 20% of that of the LRS on late AMD. Our findings show that metabolomic profiles differ between AMD stages and show that blood metabolites mostly reflect lifestyle. The severity-specific profiles spur further interest into the systemic effects related to disease conversion.},
}
@article {pmid37366063,
year = {2023},
author = {Sun, R and Zhu, H and Wang, Y and Wang, J and Jiang, C and Cao, Q and Zhang, Y and Zhang, Y and Yuan, S and Liu, Q},
title = {Circular RNA expression and the competitive endogenous RNA network in pathological, age-related macular degeneration events: A cross-platform normalization study.},
journal = {Journal of biomedical research},
volume = {37},
number = {5},
pages = {367-381},
pmid = {37366063},
issn = {1674-8301},
abstract = {Age-related macular degeneration (AMD) causes irreversible blindness in people aged over 50 worldwide. The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD. In the current study, we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database. We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis. Peroxisome and tumor necrosis factor-α (TNF-α) signaling and nuclear factor kappa B (NF-κB) were among the top 10 pathways, and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs (circRNAs). We then constructed a competing endogenous RNA network, which is related to differentially expressed circRNAs. This network included seven circRNAs, 15 microRNAs, and 82 mRNAs. The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was a common downstream event. The results of the current study may provide insights into the pathological processes of atrophic AMD.},
}
@article {pmid37364214,
year = {2023},
author = {Siotto-Pintor, E and Tatti, F and Peiretti, E},
title = {AMNIOTIC MEMBRANE TRANSPLANT IN A PATIENT WITH RECURRENT MACULAR HOLE AND ATROPHIC AGE-RELATED MACULAR DEGENERATION.},
journal = {Retinal cases &amp; brief reports},
volume = {17},
number = {4},
pages = {482-485},
doi = {10.1097/ICB.0000000000001227},
pmid = {37364214},
issn = {1937-1578},
mesh = {Male ; Humans ; Aged ; *Retinal Perforations/diagnosis/surgery/etiology ; *Geographic Atrophy/complications ; Amnion ; Retina ; Postoperative Complications ; Vitrectomy/adverse effects ; Retrospective Studies ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To report a case of a recurrent macular hole (MH) and atrophic age-related macular degeneration in a patient, treated with human amniotic membrane transplant.<br><br>METHODS: Interventional case report.<br><br>RESULTS: A 72-year-old man was referred to our Retina Unit for a recurrent MH associated with atrophic age-related macular degeneration. The patient was already operated for a full-thickness MH without any anatomical and functional benefit. A 25-gauge vitrectomy, under local anesthesia was performed. A human amniotic membrane patch was transplanted under the retina through a 180&#xb0; retinectomy to close the MH and eventually exploit his regenerative effects on the atrophic pigment epithelium. Follow-up was taken at 1, 3, and 6 months and 1 year. No intra- or postoperative complications were recorded. At 1 month, a complete MH closure was achieved, and best-corrected visual acuity increased from 20/400 to 20/320. Unfortunately, after 1 year, the macular atrophic area increased and the best-corrected visual acuity came back to 20/400.<br><br>CONCLUSION: A human amniotic membrane was used to close a MH in a patient with atrophic age-related macular degeneration, although progression of the geographic atrophy continued after MH closure.},
}
@article {pmid37364069,
year = {2023},
author = {Komarova, TM and Vitovska, OP and Komisarenko, YI and Scholtz, SK},
title = {VITAMIN D LEVEL AND ITS LINK WITH VISUAL ACUITY AND CONTRAST SENSITIVITY IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION.},
journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)},
volume = {76},
number = {5 pt 2},
pages = {1173-1178},
doi = {10.36740/WLek202305206},
pmid = {37364069},
issn = {0043-5147},
mesh = {Humans ; Female ; Infant ; Contrast Sensitivity ; *Macular Degeneration ; Visual Acuity ; Vitamins ; Vitamin D ; *Vitamin D Deficiency ; },
abstract = {OBJECTIVE: The aim: Determination of vitamin D level and its connection with visual functions in patients with age-related macular degeneration, dry form.<br><br>PATIENTS AND METHODS: Materials and methods: We analyzed the data of studies (25(OH)D3 levels (nmol/l), LogMAR visual acuity and Logarithmic contrast sensitivity) of 2 groups of women of postmenopausal age: 1 group (58 people - 58 eyes) - patients with age-related macular degeneration (dry form) - study group; 2 group (29 people - 29 eyes) - people without ophthalmic pathology - control group.<br><br>RESULTS: Results: In the study group, 37 patients (63,8%) had vitamin D deficiency, 21 people (36,2%) had vitamin D insufficiency. In the control group, these figures were 69% and 31%, respectively. These indicators were defined as low (the normal supply of vitamin D is considered to be 100 nmol/l and more). Visual acuity due to ETDRS chart in the study group was 0,22&#xb1;0,04 (in patients with vitamin D deficiency) and 0,12&#xb1;0,03 (in patients with vitamin D insuffi&#xac;ciency), in the control group - 0,13&#xb1;0,04 and 0,05&#xb1;0,04 respectively. In the control group, the logarithmic values of contrast sensitivity (log CS) were 1,58&#xb1;0,04 log CS (in patients with vitamin D deficiency) and 1,62&#xb1;0,02 log CS (in patients with vitamin D insufficiency). For patients from the study group, these figures were reduced to 0,98&#xb1;0,1 log CS and 1,10&#xb1;0,06 log CS respectively.<br><br>CONCLUSION: Conclusions: Patients with age-related macular degeneration, dry form, have low levels of vitamin D, with a predominance of its deficiency. It has been determined that with age-related macular degeneration, functional losses are observed when perceiving objects of low contrast.},
}
@article {pmid37359546,
year = {2023},
author = {Busch, C and Rau, S and Sekulic, A and Perie, L and Huber, C and Gehrke, M and Joussen, AM and Zipfel, PF and Wildner, G and Skerka, C and Strauß, O},
title = {Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1200725},
pmid = {37359546},
issn = {1664-3224},
mesh = {Male ; Female ; Humans ; *Complement Membrane Attack Complex/genetics ; Complement Factor H/metabolism ; *Macular Degeneration/pathology ; Genotype ; Cytokines/genetics ; },
abstract = {PURPOSE: Polymorphisms in complement genes are risk-associated for age-related macular degeneration (AMD). Functional analysis revealed a common deficiency to control the alternative complement pathway by risk-associated gene polymorphisms. Thus, we investigated the levels of terminal complement complex (TCC) in the plasma of wet AMD patients with defined genotypes and the impact of the complement activation of their plasma on second-messenger signaling, gene expression, and cytokine/chemokine secretion in retinal pigment epithelium (RPE) cells.<br><br>DESIGN: Collection of plasma from patients with wet AMD (n = 87: 62% female and 38% male; median age 77 years) and controls (n = 86: 39% female and 61% male; median age 58 years), grouped for risk factor smoking and genetic risk alleles CFH 402HH and ARMS2 rs3750846, determination of TCC levels in the plasma, in vitro analysis on RPE function during exposure to patients' or control plasma as a complement source.<br><br>METHODS: Genotyping, measurement of TCC concentrations, ARPE-19 cell culture, Ca[2+] imaging, gene expression by qPCR, secretion by multiplex bead analysis of cell culture supernatants.<br><br>MAIN OUTCOME MEASURES: TCC concentration in plasma, intracellular free Ca[2+], relative mRNA levels, cytokine secretion.<br><br>RESULTS: TCC levels in the plasma of AMD patients were five times higher than in non-AMD controls but did not differ in plasma from carriers of the two risk alleles. Complement-evoked Ca[2+] elevations in RPE cells differed between patients and controls with a significant correlation between TCC levels and peak amplitudes. Comparing the Ca[2+] signals, only between the plasma of smokers and non-smokers, as well as heterozygous (CFH 402YH) and CFH 402HH patients, revealed differences in the late phase. Pre-stimulation with complement patients' plasma led to sensitization for complement reactions by RPE cells. Gene expression for surface molecules protective against TCC and pro-inflammatory cytokines increased after exposure to patients' plasma. Patients' plasma stimulated the secretion of pro-inflammatory cytokines in the RPE.<br><br>CONCLUSION: TCC levels were higher in AMD patients but did not depend on genetic risk factors. The Ca[2+] responses to patients' plasma as second-messenger represent a shift of RPE cells to a pro-inflammatory phenotype and protection against TCC. We conclude a substantial role of high TCC plasma levels in AMD pathology.},
}
@article {pmid37359372,
year = {2023},
author = {Nardone, GG and Spedicati, B and Concas, MP and Santin, A and Morgan, A and Mazzetto, L and Battaglia-Parodi, M and Girotto, G},
title = {Identifying missing pieces in color vision defects: a genome-wide association study in Silk Road populations.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1161696},
pmid = {37359372},
issn = {1664-8021},
abstract = {Introduction: Color vision defects (CVDs) are conditions characterized by the alteration of normal trichromatic vision. CVDs can arise as the result of alterations in three genes (OPN1LW, OPN1MW, OPN1SW) or as a combination of genetic predisposition and environmental factors. To date, apart from Mendelian CVDs forms, nothing is known about multifactorial CVDs forms. Materials and Methods: Five hundred and twenty individuals from Silk Road isolated communities were genotyped and phenotypically characterized for CVDs using the Farnsworth D-15 color test. The CVDs traits Deutan-Protan (DP) and Tritan (TR) were analysed. Genome Wide Association Study for both traits was performed, and results were corrected with a False Discovery Rate linkage-based approach (FDR-p). Gene expression of final candidates was investigated using a published human eye dataset, and pathway analysis was performed. Results: Concerning DP, three genes: PIWIL4 (FDR-p: 9.01*10[-9]), MBD2 (FDR-p: 4.97*10[-8]) and NTN1 (FDR-p: 4.98*10[-8]), stood out as promising candidates. PIWIL4 is involved in the preservation of Retinal Pigmented Epithelium (RPE) homeostasis while MBD2 and NTN1 are both involved in visual signal transmission. With regards to TR, four genes: VPS54 (FDR-p: 4.09*10[-9]), IQGAP (FDR-p: 6,52*10[-10]), NMB (FDR-p: 8.34*10[-11]), and MC5R (FDR-p: 2.10*10[-8]), were considered promising candidates. VPS54 is reported to be associated with Retinitis pigmentosa; IQGAP1 is reported to regulate choroidal vascularization in Age-Related Macular Degeneration; NMB is involved in RPE homeostasis regulation; MC5R is reported to regulate lacrimal gland function. Discussion: Overall, these results provide novel insights regarding a complex phenotype (i.e., CVDs) in an underrepresented population such as Silk Road isolated communities.},
}
@article {pmid37356647,
year = {2023},
author = {Sajiki, AF and Koyanagi, Y and Ushida, H and Kawano, K and Fujita, K and Okuda, D and Kawabe, M and Yamada, K and Suzumura, A and Kachi, S and Kaneko, H and Komatsu, H and Usui, Y and Goto, H and Nishiguchi, KM},
title = {Association Between Torque Teno Virus and Systemic Immunodeficiency in Patients With Uveitis With a Suspected Infectious Etiology.},
journal = {American journal of ophthalmology},
volume = {254},
number = {},
pages = {80-86},
doi = {10.1016/j.ajo.2023.06.012},
pmid = {37356647},
issn = {1879-1891},
mesh = {Humans ; Cross-Sectional Studies ; *Cytomegalovirus Retinitis ; DNA, Viral/analysis ; *Epstein-Barr Virus Infections/complications/diagnosis ; Herpesvirus 4, Human/genetics ; Retrospective Studies ; *Torque teno virus/genetics ; *Uveitis/complications/diagnosis ; Male ; Female ; },
abstract = {PURPOSE: To determine the correlation between the presence of torque teno virus (TTV) in the aqueous humor of patients with uveitis and clinical information, including immunodeficiency history.<br><br>DESIGN: Multicenter, retrospective, cross-sectional study.<br><br>METHODS: Fifty-eight patients with uveitis with a suspected infectious etiology and 24 controls with cataract or age-related macular degeneration were included. We used quantitative polymerase chain reaction to test all subjects for TTV and multiplex polymerase chain reaction to test uveitis subjects for common ocular pathogens. When possible, both serum and aqueous humor samples were tested. Ocular TTV positivity was compared with age, sex, and a history of systemic immunodeficiency with logistic analysis.<br><br>RESULTS: Ocular TTV positivity was found in 23%, 11%, and 0% of patients with herpetic uveitis, nonherpetic uveitis, and controls, respectively. Among patients with herpes infection, positivity for ocular TTV was found in 43%, 8%, 14%, and 50% of patients with cytomegalovirus retinitis, iridocyclitis, acute retinal necrosis, and Epstein-Barr virus-positive uveitis, respectively. Patients with cytomegalovirus retinitis showed a significantly higher rate of ocular TTV infection than controls (P&#xa0;=&#xa0;.008). Serum analysis revealed TTV positivity in 90% of patients with uveitis and in 100% of controls. Age- and gender-adjusted logistic analysis revealed a correlation between ocular TTV positivity and systemic immunodeficiency (P&#xa0;=&#xa0;.01), but no correlations between ocular TTV and age, gender, or viral pathogenic type.<br><br>CONCLUSIONS: These findings suggest that positivity for ocular TTV was correlated with a clinical history of systemic immunodeficiency.},
}
@article {pmid37356095,
year = {2023},
author = {Sirotko, ML and Denisenko, MB and Zolotovskaya, IA and Komarova, MV},
title = {[Frequency of selected chronic noncommunicable diseases in older patients with senile asthenia syndrome.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {36},
number = {2},
pages = {198-205},
pmid = {37356095},
issn = {1561-9125},
mesh = {Aged ; Humans ; *Frailty/diagnosis/epidemiology ; Prospective Studies ; *Noncommunicable Diseases/epidemiology ; Frail Elderly ; *Diabetes Mellitus/epidemiology ; Syndrome ; Asthenia/epidemiology ; },
abstract = {An important area of medical and social research is prospective studies of a cohort of older patients with chronic non-communicable diseases aimed at studying the level of mortality, taking into account the presence/absence of senile asthenia syndrome. A prospective clinical and epidemiological study was conducted on 1 261 people aged 80 years and older receiving medical care on an outpatient basis. Three groups of patients were formed: without senile asthenia syndrome (7,6%), in a state of pre-asthenia (23,5%), with senile asthenia (68,9%). After a calendar year, an analysis was made of the causes of death of respondents in all three groups. A high statistically significant incidence of chronic diseases in patients with senile asthenia syndrome compared with those without signs of this syndrome was noted in arterial hypertension, chronic heart failure, osteoarthritis, age-related macular degeneration, chronic kidney disease, dementia, cancer, anemia, uncomplicated diabetes mellitus. In the structure of causes of death in patients aged 80 years and older, diseases of the circulatory system, nervous system, neoplasms, liver diseases, and diabetes mellitus predominated. The odds ratio of the risk of dying within a year in patients without frailty syndrome is 0,32 (compared to patients with frailty, in which the risk is taken as 1).},
}
@article {pmid37352398,
year = {2023},
author = {O'Riordan, M and Hudson, N and O'Callaghan, J and Campbell, M and Cahill, M},
title = {Near-Complete Drusen Resolution With Brolucizumab: A Mechanism for Proinflammatory Mediated Drusen Clearance?.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {6},
pages = {371-374},
doi = {10.3928/23258160-20230524-02},
pmid = {37352398},
issn = {2325-8179},
mesh = {Female ; Humans ; Aged ; Retina ; *Retinal Drusen/diagnosis/drug therapy ; Antibodies, Monoclonal, Humanized/adverse effects ; *Retinal Detachment/diagnosis/drug therapy ; *Wet Macular Degeneration ; },
abstract = {A 68-year-old woman with macular drusen was diagnosed with neovascular age-related macular degeneration (AMD) and treated with intravitreal brolucizumab. She had a good response to treatment with reduced height of the pigment epithelial detachment, and a good visual outcome. Remarkably, she had a near-complete resolution of macular drusen, yet this was accompanied by the development of anterior uveitis. We propose a proinflammatory-based mechanism for the brolucizumab-induced drusen resorption. Identifying the biochemical pathways responsible could hold the potential to discover novel forms of therapy for the treatment of AMD. [Ophthalmic Surg Lasers Imaging Retina 2023;54:371-374.].},
}
@article {pmid37349689,
year = {2023},
author = {Singh, RP and Welch, L and Longo, NL and Frese, M},
title = {Impact of an immersive, interactive medical education initiative on guideline-based retinal disease management knowledge/competence and effectual practice change.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {285},
pmid = {37349689},
issn = {1471-2415},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; *Macular Edema/drug therapy ; *Diabetic Retinopathy/diagnosis/drug therapy ; Vascular Endothelial Growth Factor A ; Retina ; Intravitreal Injections ; Disease Management ; *Education, Medical ; },
abstract = {BACKGROUND: Retinal diseases, including wet or dry age-related macular degeneration, diabetic macular edema, and diabetic retinopathy (DR), are underdiagnosed and undertreated in the United States. Clinical trials support the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapies for several retinal conditions, but real-world data suggest underuse by clinicians, resulting in patients experiencing poorer visual outcomes over time. Continuing education (CE) has demonstrated effectiveness at changing practice behaviors, but more research is needed to understand whether CE can help address diagnostic and treatment gaps.<br><br>METHODS: This test and control matched pair analysis examined pre-/post-test knowledge of retinal diseases and guideline-based screening and intervention among 10,786 healthcare practitioners (i.e., retina specialists, ophthalmologists, optometrists, primary care providers, diabetes educators, pharmacists/managed care specialists, and other healthcare providers, such as registered nurses, nurse practitioners, and physician assistants) who participated in a modular, interactive CE initiative. An additional medical claims analysis provided data on practice change, evaluating use of VEGF-A inhibitors among retina specialist and ophthalmologist learners (n&#x2009;=&#x2009;7,827) pre-/post-education, compared to a matched control group of non-learners. Outcomes were pre-/post-test change in knowledge/competence and clinical change in application of anti-VEGF therapy, as identified by the medical claims analysis.<br><br>RESULTS: Learners significantly improved knowledge/competence scores on early identification and treatment, identifying patients who could benefit from anti-VEGF agents, using guideline-recommended care, recognizing the importance of screening and referral, and recognizing the importance of early detection and care for DR (all P-values&#x2009;=&#x2009;0.003 to 0.004). Compared with matched controls, learners' incremental total injections for anti-VEGF agents for retinal conditions increased more after the CE intervention (P&#x2009;<&#x2009;0.001); specifically, there were 18,513 more (new) anti-VEGF injections prescribed versus non-learners (P&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: This modular, interactive, immersive CE initiative resulted in significant knowledge/competence gains among retinal disease care providers and changes in practice-related treatment behaviors (i.e., appropriate consideration and greater incorporation of guideline-recommended anti-VEGF therapies) among participating ophthalmologists and retina specialists compared to matched controls. Future studies will utilize medical claims data to show longitudinal impact of this CE initiative on treatment behavior among specialists and impact on diagnosis and referral rates among optometrists and primary care providers who participate in future programming.},
}
@article {pmid37348673,
year = {2023},
author = {Li, D and Wei, TT and Cai, J and Xie, TH and Yao, Y and Zhu, L},
title = {Smurf1: A possible therapeutic target in dry age-related macular degeneration.},
journal = {Experimental eye research},
volume = {233},
number = {},
pages = {109549},
doi = {10.1016/j.exer.2023.109549},
pmid = {37348673},
issn = {1096-0007},
mesh = {Humans ; Animals ; Mice ; *NF-kappa B/metabolism ; Transforming Growth Factor beta1/metabolism ; beta-Transducin Repeat-Containing Proteins/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Mice, Inbred C57BL ; Ubiquitin-Protein Ligases/genetics ; Ubiquitination ; *Macular Degeneration ; Inflammation ; Ubiquitins/metabolism ; },
abstract = {Smad ubiquitylation regulatory factor-1 (Smurf1) is one of C2-WW-HECT domain E3 ubiquitin ligases, it can regulate BMP pathway by mediating ubiquitylation degradation of Smad1/Smad5. Many functions about Smurf1 also are still unknown, especially in retina. This research is about to explore the role of Smurf1 in retina degeneration. Tail vein injection of sodium iodate (NaIO3) in C57BL/6J mice was the animal model of retina degeneration. In NaIO3 model, Smurf1 had more expression than normal mice. Specific Smurf1 inhibitor, A01, was injected into vitreous cavity. Results showed that inhibiting Smurf1 could alleviate acute retina injury, such as keeping a better retina structure in living imaging and histologic sections, less cell death and inflammation activation. Tert-butyl hydroperoxide (TBH) was used to establish oxidative stress injury in human retinal pigments epithelial cell line (ARPE-19). Oxidative stress injury gradually caused co-upregulation of Smurf1, TGF-β1 and phosphorylated NF-κB (pNF-κB). TGF-β1 could directly induce Smurf1 expression. Inhibiting Smurf1 had an anti-epithelial mesenchymal transition (anti-EMT) function. Similarly, A01 also could inhibit the expression of pNF-κB, NLRP3 and IL-1β. At last, after searching bioinformatics database, Smurf1 had a possible interaction with beta-transducin repeat containing E3 ubiquitin protein ligase (β-TrCP), another E3 ubiquitin ligases. β-TrCP can mediate ubiquitination degradation of p-IκBα. Lentivirus-SMURF1 was used to overexpress Smurf1, and GS143 was used to inhibit β-TrCP. The results showed Smurf1 could directly induce NF-κB, pNF-κB, and NLRP3 expression, and keep a stable β-TrCP expression. However, inhibiting β-TrCP could cause more NF-κB activation and NLRP3 expression. Therefore, β-TrCP may play a negative role in NF-κB pathway activation. In summary, Smurf1 plays a role in exacerbating oxidative stress injury and inflammation in retina and may become a potential therapeutic target in ROS injury of retina.},
}
@article {pmid37348500,
year = {2023},
author = {Han, X and Lains, I and Li, J and Li, J and Chen, Y and Yu, B and Qi, Q and Boerwinkle, E and Kaplan, R and Thyagarajan, B and Daviglus, M and Joslin, CE and Cai, J and Guasch-Ferré, M and Tobias, DK and Rimm, E and Ascherio, A and Costenbader, K and Karlson, E and Mucci, L and Eliassen, AH and Zeleznik, O and Miller, J and Vavvas, DG and Kim, IK and Silva, R and Miller, J and Hu, F and Willett, W and Lasky-Su, J and Kraft, P and Richards, JB and MacGregor, S and Husain, D and Liang, L},
title = {Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.},
journal = {Cell reports. Medicine},
volume = {4},
number = {7},
pages = {101085},
pmid = {37348500},
issn = {2666-3791},
support = {R00 DK122128/DK/NIDDK NIH HHS/United States ; N01 HC065236/HL/NHLBI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; R01 EY030088/EY/NEI NIH HHS/United States ; N01 HC065234/HL/NHLBI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R01 AR049880/AR/NIAMS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; R01 CA049449/CA/NCI NIH HHS/United States ; N01 HC065237/HL/NHLBI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; N01 HC065233/HL/NHLBI NIH HHS/United States ; N01 HC065235/HL/NHLBI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Genome-Wide Association Study ; Bayes Theorem ; *Macular Degeneration/genetics/metabolism ; Metabolomics ; Metabolome/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.},
}
@article {pmid37347465,
year = {2023},
author = {Vongsachang, H and Stagner, AM and Aronow, ME and Wolkow, N},
title = {Extrascleral Extension of Uveal Melanoma Along Intravitreal Needle Tracts Associated With Periodic Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {141},
number = {8},
pages = {801-803},
doi = {10.1001/jamaophthalmol.2023.2521},
pmid = {37347465},
issn = {2168-6173},
mesh = {*Choroidal Neovascularization/drug therapy ; *Wet Macular Degeneration/drug therapy ; Uveal Neoplasms ; Humans ; Angiogenesis Inhibitors/therapeutic use ; Melanoma ; *Macular Degeneration/drug therapy ; Retrospective Studies ; Ranibizumab/therapeutic use ; Intravitreal Injections ; Endothelial Growth Factors/therapeutic use ; Uveal Melanoma ; },
}
@article {pmid37347455,
year = {2023},
author = {Shome, I and Thathapudi, NC and Aramati, BMR and Kowtharapu, BS and Jangamreddy, JR},
title = {Stages, pathogenesis, clinical management and advancements in therapies of age-related macular degeneration.},
journal = {International ophthalmology},
volume = {43},
number = {10},
pages = {3891-3909},
pmid = {37347455},
issn = {1573-2630},
mesh = {Aged ; Animals ; Humans ; *Macular Degeneration/pathology ; Retina/pathology ; Retinal Pigment Epithelium/pathology ; Neovascularization, Pathologic/pathology ; },
abstract = {Age-related macular degeneration (AMD) is a retinal degenerative disorder prevalent in the elderly population, which leads to the loss of central vision. The disease progression can be managed, if not prevented, either by blocking neovascularization ("wet" form of AMD) or by preserving retinal pigment epithelium and photoreceptor cells ("dry" form of AMD). Although current therapeutic modalities are moderately successful in delaying the progression and management of the disease, advances over the past years in regenerative medicine using iPSC, embryonic stem cells, advanced materials (including nanomaterials) and organ bio-printing show great prospects in restoring vision and efficient management of either forms of AMD. This review focuses on the molecular mechanism of the disease, model systems (both cellular and animal) used in studying AMD, the list of various regenerative therapies and the current treatments available. The article also highlights on the recent clinical trials using regenerative therapies and management of the disease.},
}
@article {pmid37344061,
year = {2023},
author = {Jaggi, D and Solberg, Y and Dysli, C and Lincke, J and Habra, O and Wyss, A and Wolf, S and Zinkernagel, M},
title = {Fluorescence lifetime imaging ophthalmoscopy and the influence of oral lutein/zeaxanthin supplementation on macular pigment (FLOS) - A pilot study.},
journal = {Clinical nutrition ESPEN},
volume = {56},
number = {},
pages = {127-134},
doi = {10.1016/j.clnesp.2023.05.009},
pmid = {37344061},
issn = {2405-4577},
mesh = {Humans ; Lutein ; *Macular Pigment/metabolism ; Zeaxanthins ; Pilot Projects ; Prospective Studies ; Cohort Studies ; *Macular Degeneration/drug therapy ; Dietary Supplements ; Ophthalmoscopy ; },
abstract = {BACKGROUND &amp; AIMS: Oral lutein (L) and zeaxanthin (Z) supplementation enhances macular pigment optical density (MPOD) and plays a protective role in the development of age-related macular degeneration (AMD). Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel in vivo retinal imaging method that has been shown to correlate to classical MPOD measurements and might contribute to a metabolic mapping of the retina in the future. Our aim was to show that oral supplementation of L and Z affects the FLIO signal in a positive way in patients with AMD.<br><br>METHODS: This was a prospective, single center, open label cohort study. Patients with early and intermediate AMD received oral L and Z supplementation during three months, and were observed for another three months after therapy termination. All visits included measurements of clinical parameters, serum L and Z concentration, MPOD measurements using heterochromatic flicker photometry, dual wavelength autofluorescence imaging, and FLIO. Correlation analysis between FLIO and MPOD were performed.<br><br>RESULTS: Twenty-one patients completed the follow up period. Serum L and Z concentrations significantly increased during supplementation (mean difference 244.8&#xa0;ng/ml; 95% CI: 81.26-419.9, and 77.1&#xa0;ng/ml; 95% CI: 5.3-52.0, respectively). Mean MPOD units significantly increased (mean difference 0.06; 95% CI: 0.02-0.09; at 0.5&#xb0;, 202; 95% CI: 58-345; at 2&#xb0;, 1033; 95% CI: 288-1668; at 9&#xb0; of eccentricity, respectively) after three months of supplementation with macular xanthophylls, which included L and Z. Median FLIO lifetimes in the foveal center significantly decreased from 277.3&#xa0;ps (interquartile range 230.2-339.1) to 261.0&#xa0;ps (interquartile range 231.4-334.4, p&#xa0;=&#xa0;0.027). All parameters returned to near-normal values after termination of the nutritional supplementation. A significant negative correlation was found between FLIO and MPOD (r[2]&#xa0;=&#xa0;0.57, p&#xa0;<&#xa0;0.0001).<br><br>CONCLUSIONS: FLIO is able to detect subtle changes in MPOD after L and Z supplementation in patients with early and intermediate AMD. Our findings confirm the previous described negative correlation between FLIO and MPOD. Macular xanthophylls seem to contribute to short foveal lifetimes. This study is registered at ClinicalTrials.gov (identifier number NCT04761341).},
}
@article {pmid37343623,
year = {2023},
author = {Bodaghi, B and Souied, EH and Tadayoni, R and Weber, M and Ponthieux, A and Kodjikian, L},
title = {Detection and Management of Intraocular Inflammation after Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {10},
pages = {879-891},
doi = {10.1016/j.oret.2023.06.009},
pmid = {37343623},
issn = {2468-6530},
mesh = {Humans ; Adrenal Cortex Hormones ; Inflammation ; *Macular Degeneration/diagnosis/drug therapy ; Prospective Studies ; Retina ; *Uveitis ; *Vasculitis ; },
abstract = {PURPOSE: To present interim descriptive insights from the OCTOPUS and SWIFT studies on incidence, clinical features, management, and outcomes of intraocular inflammation (IOI), vasculitis, and occlusive vasculitis with brolucizumab treatment (Beovu, Novartis) in patients with neovascular age-related macular degeneration (nAMD) who were anti-VEGF naive or pretreated with anti-VEGFs (ranibizumab or aflibercept).<br><br>DESIGN: OCTOPUS (NCT04239027) and SWIFT (NCT04264819) studies are prospective phase IIIb single-arm, open-label, multicenter studies assessing brolucizumab.<br><br>SUBJECTS: Anti-VEGF naive (OCTOPUS) and pretreated (SWIFT) patients with nAMD.<br><br>METHODS: Interim prespecified analysis on the efficacy end point provided an opportunity to analyze IOI-related safety. Reports of IOI-related adverse events (AEs) were reviewed, and AE images and clinical features and outcomes of each case were analyzed by a review committee.<br><br>RESULTS: Of 505 brolucizumab-treated eyes/patients with median brolucizumab treatment of 8.8 months, 53 eyes demonstrated at least 1 IOI-related AE. The incidence of overall IOI-related AEs was 10.5%; among these events, the incidence was 7.1% for IOI only without retinal involvement and 3.4% for IOI with retinal involvement (2.0% with vasculitis, 1.4% with vascular occlusion with or without vasculitis). Incidence was similar in naive and pretreated patients. Before the onset of the first IOI-related AE, eyes received a median of 2 brolucizumab injections; 81.1% of IOI-related AEs occurred during the loading phase (median, 25.0 days from the last brolucizumab injection). At AE onset, most frequently reported symptoms were floaters (52.8%) and blurred or decreased vision (37.8%). Of the 86.8% of AEs that were treated, most were treated with topical corticosteroids (75.5%), 28.3% by systemic corticosteroids, and 26.8% by intraocular corticosteroids. No severe vision loss was reported for the 7 nontreated AEs. Overall, the median best-corrected visual acuity (BCVA) change at IOI-related AEs resolution from baseline was 1 letter (range,&#xa0;-74 to&#xa0;+32 letters), and 2 patients with occlusive vasculitis had BCVA loss &#x2265; 15 letters due to IOI-related AEs. All eyes permanently discontinued brolucizumab after the first IOI-related AE.<br><br>CONCLUSIONS: This analysis highlights the need for monitoring and education of patients to report any signs of IOI-related events immediately when being treated with brolucizumab. IOI should be treated promptly and intensely with corticosteroids.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37343273,
year = {2024},
author = {Vidal, C and Robles, I and Escamilla, N and Losada, D and Serrano, C and Miranda, C and Pastor, AI and Carreño, E},
title = {Hypopyon Uveitis as a Manifestation of Primary Choroidal Lymphoma.},
journal = {Ocular immunology and inflammation},
volume = {32},
number = {7},
pages = {1462-1464},
doi = {10.1080/09273948.2023.2220786},
pmid = {37343273},
issn = {1744-5078},
mesh = {Humans ; Female ; Aged ; *Choroid Neoplasms/diagnosis/drug therapy ; *Tomography, Optical Coherence ; *Fluorescein Angiography ; Rituximab/therapeutic use ; Magnetic Resonance Imaging ; Aqueous Humor ; Visual Acuity/physiology ; Uveitis/diagnosis/drug therapy ; Intravitreal Injections ; Antineoplastic Agents, Immunological/therapeutic use ; },
abstract = {A 78-year-old female was referred to our hospital due to a decrease of visual acuity in her left eye. On examination, presence of left choroidal folds and subretinal fluid was disclosed. After being misdiagnosed as neovascular age-related macular degeneration treatment with intravitreal injections of Aflibercept was started. Despite improvement of fluid, persistence of choroidal folds encouraged a magnetic resonance imaging revealing a left retrobulbar nodular lesion. Furthermore, development of hypopyon during follow-up allowed a flow cytometry analysis of an aqueous humour sample that confirmed infiltration by a non-Hodgkin mature B-cell lymphoproliferative process. Finally, treatment with Rituximab and intravenous corticosteroids achieved complete resolution. Primary choroidal lymphoma may occur with an atypical presentation, including hypopyon uveitis. Thus, familiarity with its clinical features is fundamental for an early recognition and correct management.},
}
@article {pmid37342683,
year = {2023},
author = {Rivail, A and Vogl, WD and Riedl, S and Grechenig, C and Coulibaly, LM and Reiter, GS and Guymer, RH and Wu, Z and Schmidt-Erfurth, U and Bogunović, H},
title = {Deep survival modeling of longitudinal retinal OCT volumes for predicting the onset of atrophy in patients with intermediate AMD.},
journal = {Biomedical optics express},
volume = {14},
number = {6},
pages = {2449-2464},
pmid = {37342683},
issn = {2156-7085},
abstract = {In patients with age-related macular degeneration (AMD), the risk of progression to late stages is highly heterogeneous, and the prognostic imaging biomarkers remain unclear. We propose a deep survival model to predict the progression towards the late atrophic stage of AMD. The model combines the advantages of survival modelling, accounting for time-to-event and censoring, and the advantages of deep learning, generating prediction from raw 3D OCT scans, without the need for extracting a predefined set of quantitative biomarkers. We demonstrate, in an extensive set of evaluations, based on two large longitudinal datasets with 231 eyes from 121 patients for internal evaluation, and 280 eyes from 140 patients for the external evaluation, that this model improves the risk estimation performance over standard deep learning classification models.},
}
@article {pmid37341070,
year = {2024},
author = {Kiljunen, O and Välimäki, T and Savela, RM and Koponen, S and Nykänen, I and Suominen, AL and Schwab, U},
title = {Prevalence and risk factors of frailty among older family caregivers.},
journal = {Scandinavian journal of caring sciences},
volume = {38},
number = {1},
pages = {57-64},
doi = {10.1111/scs.13190},
pmid = {37341070},
issn = {1471-6712},
support = {//Sirkka and Jorma Turunen Foundation/ ; },
mesh = {Humans ; Aged ; *Frailty/epidemiology/complications/diagnosis ; Caregivers ; Frail Elderly/psychology ; Prevalence ; Cross-Sectional Studies ; Nutritional Status ; Nutrition Assessment ; Risk Factors ; Geriatric Assessment ; },
abstract = {AIM: The aim of this study was to investigate the prevalence of frailty and identify the demographical and clinical factors associated with frailty among older family caregivers.<br><br>METHOD: The participants of this cross-sectional study were older family caregivers (n&#x2009;=&#x2009;125) living in Eastern Finland. Data on functional and cognitive status, depressive symptoms, nutritional status, medication, chronic diseases, stroke, and oral health were obtained. The Mini Nutritional Assessment (MNA) was used to evaluate nutritional status. Frailty status was evaluated using the abbreviated comprehensive geriatric assessment (aCGA) scale.<br><br>RESULTS: Seventy-three percent of caregivers were identified as frail. According to multivariable logistic regression, cataract, glaucoma, or macular degeneration and the MNA score were predictors of frailty. After adjusting for age, gender, and number of own teeth, the MNA score remained a significant predictor of frailty (adjusted OR&#x2009;=&#x2009;1.22, 95% CI&#x2009;=&#x2009;1.06, 1.41). As the MNA scores decreased (meaning poorer nutritional status), the risk of frailty increased.<br><br>CONCLUSIONS: The present study showed that frailty is prevalent among older family caregivers. Recognising older family caregivers with frailty or at risk of frailty is vital. It is essential to acknowledge vision problems' role in frailty and to monitor and support the nutritional status of family caregivers regularly to prevent frailty development.},
}
@article {pmid37340155,
year = {2023},
author = {Narnaware, SH and Bansal, A and Bawankule, PK and Raje, D and Chakraborty, M},
title = {Vessel density changes in choroid, chorio-capillaries, deep and superficial retinal plexues on OCTA in normal ageing and various stages of age-related macular degeneration.},
journal = {International ophthalmology},
volume = {43},
number = {10},
pages = {3523-3532},
pmid = {37340155},
issn = {1573-2630},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Aging ; Capillaries ; Choroid/blood supply ; Cross-Sectional Studies ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis ; Prospective Studies ; Retina ; *Retinal Vessels ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: To study vessel density (VD) on optical coherence tomography angiography at choroid, chorio-capillaries (CC) and various retinal levels in normal population and various stages of dry AMD and how these changes progress with increase in severity of the disease.<br><br>METHODS: Prospective, observational, cross-sectional study was done on 252 eyes of 132 patients (males: 61, females: 71) presenting to tertiary-care centre in Central India between February 2021 and January 2022. For study purpose, eyes were divided into five groups according to the size and number of the drusen, viz, Group 1: No AMD (<&#x2009;50&#xa0;years), Group 2: No AMD (>&#x2009;50&#xa0;years), Group 3: Early AMD, Group 4: Intermediate AMD and Group 5: Advanced AMD. In all eyes, VD was measured at choroid, CC, deep capillary plexus (DCP) of retina and superficial capillary plexus (SCP) of retina.<br><br>RESULTS: The mean age in case cohort is 61.90&#x2009;&#xb1;&#x2009;7.97&#xa0;years. The mean vascular density differed significantly across diagnosis types in all the quadrants (p&#x2009;<&#x2009;0.05) at choroid, CC and DCP level. At SCP level, the differences were significant across the groups except at the central quadrant. Vessel density was found to be more in early AMD cohort when compared to No AMD (>&#x2009;50&#xa0;years) cohort at SCP and DCP level, while it showed continuous reduction later in intermediate and advanced AMD cohort.<br><br>CONCLUSION: With increase in the severity of disease, significant reduction in VD is also seen in retinal plexuses, along with the changes in choroid and CC. These VD maps may play a role as non-invasive biomarkers for healthy and diseased ageing.},
}
@article {pmid37339446,
year = {2023},
author = {Matsumiya, W and Karaca, I and Pham, BH and Akhavanrezayat, A and Uludag, G and Yasar, C and Ghoraba, H and Mobasserian, A and Regenold, J and Halim, MS and Sepah, YJ and Do, DV and Chong, V and Nguyen, QD},
title = {ASSOCIATION OF ORAL MONTELUKAST WITH REDUCED ODDS OF DEVELOPING EXUDATIVE AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {11},
pages = {1914-1921},
doi = {10.1097/IAE.0000000000003870},
pmid = {37339446},
issn = {1539-2864},
mesh = {Humans ; Case-Control Studies ; *Smoking ; *Macular Degeneration/diagnosis ; },
abstract = {PURPOSE: This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development.<br><br>METHODS: This case-control study was conducted using institutional cohort finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Subanalysis among 1913 exAMD and 324 nonexudative AMD was also conducted.<br><br>RESULTS: A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use before exAMD diagnosis, compared with 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted odds ratio [OR]: 0.50, 95% confidence interval: 0.31-0.80) and nonsteroidal anti-inflammatory drug usage (adjusted OR: 0.69). Caucasian race, history of smoking, and nonexudative macular degeneration in either eye were also found to have a significant relationship with increased odds of exAMD. In the subanalysis, montelukast usage showed significant association with reduced odds of developing exAMD from nonexudative AMD (adjusted OR: 0.53, 95% confidence interval: 0.29-0.97) and the presence of atopic disease (adjusted OR: 0.60).<br><br>CONCLUSION: The study results suggested that oral montelukast is linked to reduced odds of exAMD development.},
}
@article {pmid37339216,
year = {2023},
author = {Parikh, BH and Blakeley, P and Regha, K and Liu, Z and Yang, B and Bhargava, M and Wong, DSL and Tan, QSW and Wong, CSW and Wang, HF and Al-Mubaarak, A and Chou, C and Cheung, CMG and Lim, KL and Barathi, VA and Hunziker, W and Lingam, G and Hu, TX and Su, X},
title = {Single-cell transcriptomics reveals maturation of transplanted stem cell-derived retinal pigment epithelial cells toward native state.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {26},
pages = {e2214842120},
pmid = {37339216},
issn = {1091-6490},
mesh = {Adult ; Animals ; Humans ; Rabbits ; *Transcriptome ; *Macular Degeneration/genetics/therapy ; Stem Cells ; Epithelial Cells ; Retinal Pigments ; },
abstract = {Transplantation of stem cell-derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation, and fate specification of transplanted RPE cells. To address this, we transplanted stem cell-derived RPE into the subretinal space of immunocompetent rabbits for 1 mo and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory-inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation toward the native adult human RPE state in all transplanted RPE, regardless of stem cell resource. Gene regulatory network analysis suggests that tripartite transcription factors (FOS, JUND, and MAFF) may be specifically activated in posttransplanted RPE cells, to regulate canonical RPE signature gene expression crucial for supporting host photoreceptor function, and to regulate prosurvival genes required for transplanted RPE's adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.},
}
@article {pmid37339135,
year = {2023},
author = {Ricci, FS and Boldini, A and Ma, X and Beheshti, M and Geruschat, DR and Seiple, WH and Rizzo, JR and Porfiri, M},
title = {Virtual reality as a means to explore assistive technologies for the visually impaired.},
journal = {PLOS digital health},
volume = {2},
number = {6},
pages = {e0000275},
pmid = {37339135},
issn = {2767-3170},
abstract = {Visual impairment represents a significant health and economic burden affecting 596 million globally. The incidence of visual impairment is expected to double by 2050 as our population ages. Independent navigation is challenging for persons with visual impairment, as they often rely on non-visual sensory signals to find the optimal route. In this context, electronic travel aids are promising solutions that can be used for obstacle detection and/or route guidance. However, electronic travel aids have limitations such as low uptake and limited training that restrict their widespread use. Here, we present a virtual reality platform for testing, refining, and training with electronic travel aids. We demonstrate the viability on an electronic travel aid developed in-house, consist of a wearable haptic feedback device. We designed an experiment in which participants donned the electronic travel aid and performed a virtual task while experiencing a simulation of three different visual impairments: age-related macular degeneration, diabetic retinopathy, and glaucoma. Our experiments indicate that our electronic travel aid significantly improves the completion time for all the three visual impairments and reduces the number of collisions for diabetic retinopathy and glaucoma. Overall, the combination of virtual reality and electronic travel aid may have a beneficial role on mobility rehabilitation of persons with visual impairment, by allowing early-phase testing of electronic travel aid prototypes in safe, realistic, and controllable settings.},
}
@article {pmid37337222,
year = {2023},
author = {Addo, EK and Hartnett, ME and Bernstein, PS},
title = {The value of pre-symptomatic genetic risk assessment for age-related macular degeneration: the Moran AMD Genetic Testing Assessment (MAGENTA) study-a study protocol for a randomized controlled trial.},
journal = {Trials},
volume = {24},
number = {1},
pages = {414},
pmid = {37337222},
issn = {1745-6215},
support = {UM1 TR004409/TR/NCATS NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; R21 EY033579/EY/NEI NIH HHS/United States ; EY014800/EY/NEI NIH HHS/United States ; EY033579/EY/NEI NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Lutein ; Rosaniline Dyes ; Prospective Studies ; Dietary Supplements ; Zeaxanthins ; *Macular Degeneration/diagnosis/genetics ; Carotenoids ; Risk Assessment ; Genetic Testing ; Randomized Controlled Trials as Topic ; Clinical Trials, Phase II as Topic ; Multicenter Studies as Topic ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is an irreversible blinding eye condition with complex genetic and environmental etiologies. Genetic testing for AMD for previously identified multiple-risk single nucleotide polymorphisms can help determine an individual's future susceptibility. However, such testing has been discouraged until evidence shows that providing such information to symptomatic or pre-symptomatic individuals will alter their disease course. Therefore, we designed this study to investigate whether knowledge of AMD risk could stimulate the adoption of a healthier lifestyle that could lower the incidence of AMD later in life. We hypothesize that pre-symptomatic individuals informed of a high genetic risk of AMD are more likely to make quantifiable, positive lifestyle changes relative to participants informed of lower genetic risk or randomized to deferred disclosure of genetic testing results.<br><br>METHODS: The Moran AMD Genetic Testing Assessment (MAGENTA) study is a phase 2, single-center, prospective, double-masked, randomized controlled trial conducted at the John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Participants are randomized by a 3:1 allocation ratio to immediate and deferred disclosure groups and followed for 12&#xa0;months. Skin, ocular, and serum carotenoid status, as well as nutritional and social surveys, are assessed at study visits. Skin carotenoid assessment is by resonance Raman spectroscopy and reflectance spectroscopy, ocular carotenoids are measured with Heidelberg Spectralis autofluorescence imaging and fluorescence lifetime imaging ophthalmoscopy (FLIO), and serum carotenoids are quantified using high-performance liquid chromatography. The primary outcome evaluates changes in skin carotenoid status in response to genetic risk disclosure. The secondary outcomes examine changes in ocular and serum carotenoid status in response to genetic risk disclosure. Also, we will correlate AMD genetic risk with baseline ocular and systemic carotenoid status and FLIO.<br><br>DISCUSSION: MAGENTA will provide much-needed evidence on whether pre-symptomatic testing for AMD risk can lead to quantifiable long-term changes in behavior and lifestyle associated with a lower incidence of AMD later in life. Findings from the MAGENTA trial will facilitate the design of a future larger, longer-term, multicenter phase 3 trial that could feature subgroup analysis, expanded measures of lifestyle modification, and potential active nutritional interventions.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT05265624 . Registered on March 3, 2022.},
}
@article {pmid37336979,
year = {2023},
author = {Birtel, J and Bauer, T and Pauleikhoff, L and Rüber, T and Gliem, M and Charbel Issa, P},
title = {Fundus autofluorescence imaging using red excitation light.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {9916},
pmid = {37336979},
issn = {2045-2322},
support = {/DH_/Department of Health/United Kingdom ; },
mesh = {Humans ; Lipofuscin/metabolism ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/pathology ; Fundus Oculi ; *Retinal Diseases/pathology ; Optical Imaging/methods ; Fluorescein Angiography/methods ; },
abstract = {Retinal disease accounts significantly for visual impairment and blindness. An important role in the pathophysiology of retinal disease and aging is attributed to lipofuscin, a complex of fluorescent metabolites. Fundus autofluorescence (AF) imaging allows non-invasive mapping of lipofuscin and is a key technology to diagnose and monitor retinal disease. However, currently used short-wavelength (SW) excitation light has several limitations, including glare and discomfort during image acquisition, reduced image quality in case of lens opacities, limited visualization of the central retina, and potential retinal light toxicity. Here, we establish a novel imaging modality which uses red excitation light (R-AF) and overcomes these drawbacks. R-AF images are high-quality, high-contrast fundus images and image interpretation may build on clinical experience due to similar appearance of pathology as on SW-AF images. Additionally, R-AF images may uncover disease features that previously remained undetected. The R-AF signal increases with higher abundance of lipofuscin and does not depend on photopigment bleaching or on the amount of macular pigment. Improved patient comfort, limited effect of cataract on image quality, and lack of safety concerns qualify R-AF for routine clinical monitoring, e.g. for patients with age-related macular degeneration, Stargardt disease, or for quantitative analysis of AF signal intensity.},
}
@article {pmid37336384,
year = {2023},
author = {Miller, AM and Gill, MK},
title = {A Review of the Prevalence of Ophthalmologic Diseases in Native American Populations.},
journal = {American journal of ophthalmology},
volume = {254},
number = {},
pages = {54-61},
doi = {10.1016/j.ajo.2023.06.010},
pmid = {37336384},
issn = {1879-1891},
mesh = {Humans ; *American Indian or Alaska Native ; Cross-Sectional Studies ; Indians, North American ; Prevalence ; Quality of Life ; Retrospective Studies ; United States/epidemiology ; *Vision Disorders/epidemiology/ethnology/therapy ; *Health Status Disparities ; *Healthcare Disparities/ethnology ; },
abstract = {PURPOSE: Compared with the general population in North America, Native American/American Indian and Alaska Native (AI/AN) populations experience a disparate prevalence of eye diseases. Visual impairment is a barrier to communication, interferes with academic and social success, and decreases overall quality of life. The prevalence of ocular pathology could serve as an indicator of health and social disparities. Therefore, the objective of this research was to perform a thorough review comparing the prevalence of common ophthalmological pathologies between AI/AN and non-AI/AN individuals in North America.<br><br>DESIGN: Retrospective, cross-sectional study.<br><br>METHODS: A total of 57 articles were retrieved and reviewed, and 14 met the criteria outlined for inclusion. These articles were retrieved from PubMed, MEDLINE, and ISI Web of Knowledge. Only studies that were peer reviewed in the last 25 years and reported on the prevalence of eye diseases in AI/AN compared with a non-AI/AN population met criteria.<br><br>RESULTS: Rates of retinopathy, cataracts, visual impairment, and blindness were clearly higher for AI/AN compared with non-AI/AN counterparts. Although rates of macular degeneration and glaucoma were similar between AI/AN and non-AI/AN populations, the treatment rates were lower and associated with poorer outcomes in AI/AN individuals.<br><br>CONCLUSIONS: There are considerable inequities in the prevalence and treatment rates of ophthalmologic conditions in AI/AN individuals. A likely explanation is the barrier of lack of access to adequate health and eye care. Because of substantial underinsurance and geographic variability, attention needs to be brought to expanding eye care access to AI/AN communities. The results are subject to the availability of appropriate technology, health literacy, and language.},
}
@article {pmid37335386,
year = {2023},
author = {Nordestgaard, LT and Christoffersen, M and Afzal, S and Nordestgaard, BG and Tybjærg-Hansen, A and Frikke-Schmidt, R},
title = {Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration.},
journal = {European journal of epidemiology},
volume = {38},
number = {9},
pages = {985-994},
pmid = {37335386},
issn = {1573-7284},
mesh = {Female ; Humans ; Male ; Middle Aged ; Amino Acids ; *Angiogenesis Inhibitors ; Cholesterol, HDL ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; *ATP Binding Cassette Transporter 1/genetics ; },
abstract = {Genetic variants in ABCA1 are associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are observationally and genetically associated with higher risk of age-related macular degeneration (AMD). However, whether amino acid-changing genetic variants in ABCA1 associated with high HDL cholesterol concentrations confer a higher risk of AMD in the general population is currently unknown. We tested this hypothesis. The study included 80,972 individuals (1,370 AMD cases) from the Copenhagen General Population Study (CGPS) and 9,584 individuals (142 AMD cases) from the Copenhagen City Heart Study (CCHS) with 10 to 18 years of follow-up. We created an HDL cholesterol weighted allele score based on amino acid-changing ABCA1 variants with a minor allele frequency above 0.001 and divided it into tertiles. The study included 55% women. Mean age was 58 years. The ABCA1 allele score for the third versus the first tertile was associated with HRs (95% confidence intervals (CIs)) of 1.30 (1.14-1.49) for all-cause AMD, 1.26 (1.06-1.50) for nonneovascular AMD, and 1.31 (1.12-1.53) for neovascular AMD in a multivariable adjusted model. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, nonneovascular AMD, and neovascular AMD in an age- and sex adjusted model and in a multivariable adjusted model. In conclusion, amino acid-changing genetic variants in ABCA1 associated with higher HDL cholesterol concentrations were also associated with higher risk of AMD, suggesting a role for ABCA1 in AMD pathogenesis.},
}
@article {pmid37335334,
year = {2024},
author = {Lee, D and Tomita, Y and Shinojima, A and Ban, N and Yamaguchi, S and Nishioka, K and Negishi, K and Yoshino, J and Kurihara, T},
title = {Nicotinamide mononucleotide, a potential future treatment in ocular diseases.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {3},
pages = {689-700},
pmid = {37335334},
issn = {1435-702X},
support = {15&#x2009;K10881//KAKENHI/ ; 18&#x2009;K09424//KAKENHI/ ; 20K23382//KAKENHI/ ; JPMJSP2123//JST SPRING/ ; },
mesh = {Humans ; Animals ; Mice ; Nicotinamide Mononucleotide ; Eye ; *Glaucoma ; *Macular Degeneration ; Inflammation ; },
abstract = {PURPOSE: The burden of ocular diseases has been gradually increasing worldwide. Various factors are suggested for the development and progression of ocular diseases, such as ocular inflammation, oxidative stress, and complex metabolic dysregulation. Thus, managing ocular diseases requires the modulation of pathologic signaling pathways through many mechanisms. Nicotinamide mononucleotide (NMN) is a bioactive molecule naturally found in life forms. NMN is a direct precursor of the important molecule nicotinamide adenine dinucleotide (NAD[+]), an essential co-enzyme required for enormous cellular functions in most life forms. While the recent experimental evidence of NMN treatment in various metabolic diseases has been well-reviewed, NMN treatment in ocular diseases has not been comprehensively summarized yet. In this regard, we aimed to focus on the therapeutic roles of NMN treatment in various ocular diseases with recent advances.<br><br>METHODS: How we came to our current opinion with a recent summary was described based on our own recent reports as well as a search of the related literature.<br><br>RESULTS: We found that NMN treatment might be available for the prevention of and protection from various experimental ocular diseases, as NMN treatment modulated ocular inflammation, oxidative stress, and complex metabolic dysregulation in murine models for eye diseases such as ischemic retinopathy, corneal defect, glaucoma, and age-related macular degeneration.<br><br>CONCLUSION: Our current review suggests and discusses new modes of actions of NMN for the prevention of and protection from various ocular diseases and can urge future research to obtain more solid evidence on a potential future NMN treatment in ocular diseases at the preclinical stages.},
}
@article {pmid37333491,
year = {2023},
author = {LoBue, SA and Gindina, S and Saba, NJ and Chang, T and Davis, MJ and Fish, S},
title = {Clinical Features Associated with Acute Elevated Intraocular Pressure After Intravitreal Anti-VEGF Injections.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1683-1690},
pmid = {37333491},
issn = {1177-5467},
abstract = {PURPOSE: To study the effects of intravitreal injection (IVI) of anti-VEGF (vascular endothelial growth factor) agents on intraocular pressure (IOP) and find associations with acute pressure spikes.<br><br>METHODS: This was a three-month, prospective study of patients receiving outpatient IVI of anti-VEGF agents for diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) at the Acuity Eye Group Medical Centers. IOP was measured pre- and post-injection at 10-minute intervals up to 50 minutes after injection with a handheld tonometer. Patients with an IOP greater than 35 mmHg at 30 minutes received an anterior chamber paracentesis (ACP), while patients below 35 mmHg were monitored without intervention.<br><br>RESULTS: A total of 617 patients (51% female, 49% male) received IVI for DR (n = 199), AMD (n = 355), and RVO (n = 63). ACP was performed in 17 patients. Average pre-injection IOP was 16 &#xb1; 4 compared to 24 &#xb1; 7 mmHg for the non-ACP vs ACP group, respectively (mean &#xb1; standard deviation), p < 0.0001. IOP returned to baseline in 98% of patients at 50 minutes. A diagnosis of glaucoma and glaucoma suspect was more prevalent in the ACP group compared to the non-ACP group, 82.3% vs 14.2% and 17.6% vs 9.0%, respectively, p < 0.0001 and p > 0.05. Patients with a pre-injection IOP >25 mmHg and a history of glaucoma had a 58.3% rate of ACP. A 31-gauge needle had a higher mean increase in IOP from baseline compared to 30-gauge needle, p < 0.0001.<br><br>CONCLUSION: IOP spikes are most significant in the first 10 minutes after IVI but typically resolve within the first hour. However, utilizing a smaller 31-gauge IVI in patients with a glaucoma history and pre-injection IOP >25 mmHg may be associated with significant IOP spikes lasting longer than 30 minutes.},
}
@article {pmid37333471,
year = {2023},
author = {Ansari-Mohseni, N and Ghorani-Azam, A and Mohajeri, SA},
title = {Therapeutic effects of herbal medicines in different types of retinopathies: A systematic review.},
journal = {Avicenna journal of phytomedicine},
volume = {13},
number = {2},
pages = {118-142},
pmid = {37333471},
issn = {2228-7930},
abstract = {OBJECTIVE: Retinopathy is an ocular manifestation of systemic diseases such as diabetes and vascular diseases. Herbal drugs have been considered as an effective therapeutic option with minimal side effects for the treatment of retinopathy by reducing the symptoms and improving visual acuity. The purpose of this systematic review was to collect studies on the effectiveness of medicinal plants in the treatment or prevention of retinopathy.<br><br>MATERIALS AND METHODS: A systematic literature search was performed in PubMed, Scopus, Google Scholar, and other databases in April 2021 using "herbal products" and "Retinopathy" with all their equivalent and similar terms. For this purpose, human clinical trials with the English language were included and articles with subject irrelevancy were excluded from further evaluation.<br><br>RESULTS: Overall, 30 articles with 2324 patients were studied for possible effects of herbal therapy on retinopathy. From 30 included articles, different herbal products had been evaluated. Out of 30 selected articles, 11 articles were for the treatment of age-related macular degeneration (AMD), 14 articles covered patients with diabetic retinopathy, and the other five studies were for other retinal disorders. The outcomes in majority of the studies include changes in visual acuity (VA), fundus performance, best-corrected visual acuity (BCVA), central macular thickness (CMT), focal electroretinogram (fERG), supplements and adjuvant medications appeared to be more beneficial in patients with AMD and diabetic maculopathy.<br><br>CONCLUSION: Herbal therapy can be considered as a potential candidate in the adjuvant and complementary therapies of retinopathy. However, further studies are required to verify such efficiency.},
}
@article {pmid37332546,
year = {2023},
author = {Kim, BH and Chang, IB and Yu, HG and Hong, IH},
title = {Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {16},
number = {6},
pages = {909-914},
pmid = {37332546},
issn = {2222-3959},
abstract = {AIM: To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor (VEGF) injections to treat neovascular age-related macular degeneration (nAMD) with subretinal fluid (SRF) and pigment epithelial detachment (PED).<br><br>METHODS: This prospective study included eyes with nAMD previously treated with as-needed anti-VEGF injections. The patients were treated with six monthly intravitreal injections of ranibizumab. Quantitative volumetric segmentation analyses of the SRF and PED were performed. The main outcome measures included best-corrected visual acuity (BCVA), and SRF and PED volumes.<br><br>RESULTS: Twenty eyes of 20 patients were included in this study. At the 6-month follow-up, BCVA and PED volume did not change significantly (P=0.110 and 0.999, respectively) but the mean SRF volume decreased from 0.53&#xb1;0.82 mm[3] at baseline to 0.08&#xb1;0.23 mm[3] (P=0.002). The absorption rate of the SRF volume was negatively correlated with the duration of previous anti-VEGF treatment (P=0.029). Seven of the 20 eyes (35%) showed a fluid-free macula and significant improvement in BCVA (P=0.036) by month 6.<br><br>CONCLUSION: Quantifying the SRF can precisely determine the patient's responsiveness to anti-VEGF treatment of nAMD.},
}
@article {pmid37332539,
year = {2023},
author = {Widihastha, SH and Iskandar, E and Satari, K and Irfani, I and Virgana, R and Amiruddin, PO},
title = {Vision rehabilitation using microperimetric biofeedback training in age-related macular degeneration.},
journal = {International journal of ophthalmology},
volume = {16},
number = {6},
pages = {933-938},
pmid = {37332539},
issn = {2222-3959},
abstract = {AIM: To determine the impact of microperimetric biofeedback training (MBFT) on the quality of vision in patients with age-related macular degeneration (AMD).<br><br>METHODS: This study was a prospective, interventional, comparative study with subjects of patients diagnosed with AMD in the National Eye Center Cicendo Eye Hospital, Indonesia. Patients were randomly divided into two groups, intervention and non-intervention with 18 patients in each group. The intervention group would receive six MBFT training sessions of 10-minute time duration each.<br><br>RESULTS: A statistically significant improvement of best corrected visual acuity (BCVA) was found after the intervention, from 1.24&#xb1;0.416 to 0.83&#xb1;0.242 (logMAR; P<0.001). A statistically significant improvement for near vision acuity (NVA) was also observed, from 1.02&#xb1;0.307 logMAR to 0.69&#xb1;0.278 logMAR (P<0.001). In addition, reading rate increased, from 40.83&#xb1;30.411 to 65.06&#xb1;31.598 words/min (P<0.001). Similarly, a comparison of changes in BCVA, NVA, and reading rate between intervention and non-intervention groups showed a significant difference (P<0.001).<br><br>CONCLUSION: MBFT significantly and positively impacts visual acuity, NVA, and reading rate in patients with AMD.},
}
@article {pmid37332352,
year = {2023},
author = {Gu, F and Jiang, J and Sun, P},
title = {Recent advances of exosomes in age-related macular degeneration.},
journal = {Frontiers in pharmacology},
volume = {14},
number = {},
pages = {1204351},
pmid = {37332352},
issn = {1663-9812},
abstract = {Exosomes are 30-150 nm extracellular vesicles that are secreted by almost all types of cells. Exosomes contain a variety of biologically active substances, such as proteins, nucleic acids, and lipids, and are important in the intercellular communication of biological mediators involved in nerve injury and repair, vascular regeneration, immune response, fibrosis formation, and many other pathophysiological processes. Although it has been extensively studied in the field of cancer, the exploration of ocular diseases has only just begun. Here, we discuss the latest developments in exosomes for age-related macular degeneration (AMD), including the pathogenesis of exosomes in age-related macular degeneration, their potential as diagnostic markers, and therapeutic vectors of the disease. Finally, the study of exosomes in age-related macular degeneration is still relatively few, and more detailed basic research and clinical trials are needed to verify its application in treatment and diagnosis, so as to adopt more personalized diagnosis and treatment strategies to stop the progression of age-related macular degeneration.},
}
@article {pmid37331928,
year = {2023},
author = {Parkinson, KM and Sayre, EC and Tobe, SW},
title = {Evaluation of visual acuity in dry AMD patients after microcurrent electrical stimulation.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {36},
pmid = {37331928},
issn = {2056-9920},
abstract = {BACKGROUND: To assess micro current to improve vision for dry age-related macular degeneration. Dry age-related macular degeneration is a major cause of blindness, disability, and severe erosion of quality of life, throughout the world. Beyond nutritional supplementation, there is no approved therapy.<br><br>METHODS: This was a prospective randomized sham controlled clinical trial for participants with confirmed dry AMD with documented visual loss. Participants were randomized three to one, to receive transpalpebral external micro current electrical stimulation with the MacuMira device. The Treatment group received four treatments in the first two weeks, and two further treatments at weeks 14 and 26. Differences in BCVA and contrast sensitivity (CS) were estimated with mixed-effects repeated measures analysis of variance.<br><br>RESULTS: Change of visual acuity with ETDRS assessment of number of letters read (NLR) and contrast sensitivity at week 4 and 30, compared to the first visit, between 43 treatment and 19 sham control participants. The Sham Control group had NLR of 24.2 (SD 7.1) at baseline, 24.2 (SD 7.2) at 4&#xa0;weeks, and 22.1 (SD7.4) at 30&#xa0;weeks. The Treatment group had NLR of 19.6 (SD 8.9) at baseline, 27.6 (SD 9.1) at 4&#xa0;weeks, and 27.8 (SD 8.4) at 30&#xa0;weeks. The change in NLR from baseline in the Treatment compared to the Sham control group was 7.7 (95% CI 5.7, 9.7, p&#x2009;<&#x2009;0.001) at 4&#xa0;weeks and 10.4 (95% CI 7.8, 13.1, p&#x2009;<&#x2009;0.001) at 30&#xa0;weeks. There were similar benefits in CS.<br><br>CONCLUSIONS: This pilot study of transpalpebral microcurrent demonstrated improved visual measures and is very encouraging as a potential treatment for dry AMD.<br><br>TRIAL REGISTRATION: NCT02540148, ClinicalTrials.gov.},
}
@article {pmid37330004,
year = {2023},
author = {Cristante, E and Liyanage, SE and Smith, AJ and Ali, RR and Bainbridge, JWB},
title = {Role of HIF1α and HIF2α in Cre Recombinase-Induced Retinal Pigment Epithelium Pathology and Its Secondary Effect on Choroidal Neovascularization.},
journal = {The American journal of pathology},
volume = {193},
number = {11},
pages = {1694-1705},
pmid = {37330004},
issn = {1525-2191},
abstract = {Cre[Trp1] mice are widely used for conditional retinal pigment epithelium (RPE) gene function studies. Like other Cre/LoxP models, phenotypes in Cre[Trp1] mice can be affected by Cre-mediated cellular toxicity, leading to RPE dysfunction, altered morphology and atrophy, activation of innate immunity, and consequent impairment of photoreceptor function. These effects are common among the age-related alterations of RPE that feature in early/intermediate forms of age-related macular degeneration. This article characterizes Cre-mediated pathology in the Cre[Trp1] line to elucidate the impact of RPE degeneration on both developmental and pathologic choroidal neovascularization. Nonredundant roles of the two major components of the hypoxia-inducible factor (HIF) family of transcription regulators, HIF1α and HIF2α, were identified. Genetic ablation of Hif1a protected against Cre-induced degeneration of RPE and choroid, whereas ablation of Hif2a exacerbated this degeneration. Furthermore, HIF1α deficiency protected Cre[Trp1] mice against laser-induced choroidal neovascularization, whereas HIF2α deficiency exacerbated the phenotype. Cre-mediated degeneration of the RPE in Cre[Trp1] mice offers an opportunity to investigate the impact of hypoxia signaling in the context of RPE degeneration. These findings indicate that HIF1α promotes Cre recombinase-mediated RPE degeneration and laser-induced choroidal neovascularization, whereas HIF2α is protective.},
}
@article {pmid37328798,
year = {2023},
author = {Tang, HY and Rosén, M and Granstam, E},
title = {Cataract surgery in neovascular AMD: impact on visual acuity and disease activity.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {276},
pmid = {37328798},
issn = {1471-2415},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/complications/diagnosis/drug therapy ; *Cataract/complications/drug therapy ; Tomography, Optical Coherence/methods ; Intravitreal Injections ; Ranibizumab ; },
abstract = {BACKGROUND: Cataract and neovascular age-related macular degeneration (nAMD) often co-exist and both contribute to impaired vision. It has been debated whether cataract surgery can increase nAMD activity. The purpose of this retrospective study was to investigate the impact of cataract surgery on visual acuity, treatment intensity for nAMD and macular morphology in patients with on-going treatment for nAMD.<br><br>METHODS: Data was obtained from the Swedish Macular Register, the Swedish National Cataract Register, optical coherence tomography (OCT) images and patient charts. All eyes were treated at the Department of Ophthalmology at the County Hospital of V&#xe4;stmanland, V&#xe4;ster&#xe5;s, Sweden. Follow-up was 6&#xa0;months after surgery. The study was approved by the Swedish Ethical Review Authority.<br><br>RESULTS: In total, 156 patients (168 eyes) were included. The mean age at cataract surgery was 82 (standard deviation, SD 6) years. Both distance and near visual acuity improved after surgery. Distance visual acuity increased from 59 (SD 12) to 66 (SD 15) letters ETDRS (P&#x2009;<&#x2009;0.001). Proportion of eyes with normal near visual acuity increased from 12 to 41%. The anti-vascular endothelial growth factor (VEGF) treatment intensity remained unchanged: mean of 3.4 (SD 1.9) and 3.3 (SD 1.7) treatments were given 6&#xa0;months pre- and postoperatively, respectively. The prevalence of intraretinal fluid (IRF) in the macula increased from 22 to 31% postoperatively, while subretinal fluid, fluid under the pigment epithelium (sub-RPE fluid) and central retinal thickness were unaltered. In eyes with new IRF, improvement in visual acuity and number of anti-VEGF treatments were similar to eyes without new IRF.<br><br>CONCLUSION: Cataract surgery improved visual acuity in patients with on-going treatment for nAMD and did not affect anti-VEGF treatment intensity. Macular morphology remained unchanged. The slight increase in intraretinal fluid after surgery was not found to affect visual acuity or anti-VEGF treatment intensity. It is hypothesized that this might indicate that it represents degenerative intraretinal cystic fluid.},
}
@article {pmid37328058,
year = {2024},
author = {Yang, YC and Chien, Y and Yarmishyn, AA and Lim, LY and Tsai, HY and Kuo, WC and Tsai, PH and Yang, SH and Hong, SI and Chen, SJ and Hwang, DK and Yang, YP and Chiou, SH},
title = {Inhibition of oxidative stress-induced epithelial-mesenchymal transition in retinal pigment epithelial cells of age-related macular degeneration model by suppressing ERK activation.},
journal = {Journal of advanced research},
volume = {60},
number = {},
pages = {141-157},
pmid = {37328058},
issn = {2090-1224},
mesh = {*Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/metabolism/drug therapy ; *Oxidative Stress/drug effects ; *Epithelial-Mesenchymal Transition/drug effects ; Animals ; *Iodates ; Humans ; Mice ; *Reactive Oxygen Species/metabolism ; *Disease Models, Animal ; Cell Line ; Extracellular Signal-Regulated MAP Kinases/metabolism ; MAP Kinase Signaling System/drug effects ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; ErbB Receptors/metabolism ; Epithelial Cells/metabolism/drug effects ; },
abstract = {INTRODUCTION: Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is related to the pathogenesis of various retinopathies including age-related macular degeneration (AMD). Oxidative stress is the major factor that induces degeneration of RPE cells associated with the etiology of AMD.<br><br>OBJECTIVES: Sodium iodate (NaIO3) generates intracellular reactive oxygen species (ROS) and is widely used to establish a model of AMD due to the selective induction of retinal degeneration. This study was performed to clarify the effects of multiple NaIO3-stimulated signaling pathways on EMT in RPE cells.<br><br>METHODS: The EMT characteristics in NaIO3-treated human ARPE-19 cells and RPE cells of the mouse eyes were analyzed. Multiple oxidative stress-induced modulators were investigated and the effects of pre-treatment with Ca[2+] chelator, extracellular signal-related kinase (ERK) inhibitor, or epidermal growth factor receptor (EGFR) inhibitor on NaIO3-induced EMT were determined. The efficacy of post-treatment with ERK inhibitor on the regulation of NaIO3-induced signaling pathways was dissected and its role in retinal thickness and morphology was evaluated by using histological cross-sections and spectral domain optical coherence tomography.<br><br>RESULTS: We found that NaIO3 induced EMT in ARPE-19 cells and in RPE cells of the mouse eyes. The intracellular ROS, Ca[2+], endoplasmic reticulum (ER) stress marker, phospho-ERK, and phospho-EGFR were increased in NaIO3-stimulated cells. Our results showed that pre-treatment with Ca[2+] chelator, ERK inhibitor, or EGFR inhibitor decreased NaIO3-induced EMT, interestingly, the inhibition of ERK displayed the most prominent effect. Furthermore, post-treatment with FR180204, a specific ERK inhibitor, reduced intracellular ROS and Ca[2+] levels, downregulated phospho-EGFR and ER stress marker, attenuated EMT of RPE cells, and prevented structural disorder of the retina induced by NaIO3.<br><br>CONCLUSIONS: ERK is a crucial regulator of multiple NaIO3-induced signaling pathways that coordinate EMT program in RPE cells. Inhibition of ERK may be a potential therapeutic strategy for the treatment of AMD.},
}
@article {pmid37326711,
year = {2023},
author = {Weber, S and Carruthers, N and Gates, C and Zhao, Y and Sundstrom, J},
title = {Mass Spectrometry-Based Vitreous Proteomics: Validated Methods and Analysis Pipeline.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2678},
number = {},
pages = {157-167},
pmid = {37326711},
issn = {1940-6029},
mesh = {Humans ; *Proteomics/methods ; Mass Spectrometry ; Retina/metabolism ; *Diabetic Retinopathy/diagnosis/metabolism ; Vitreous Body/metabolism ; },
abstract = {Retinal diseases like diabetic retinopathy and age-related macular degeneration affect millions of individuals worldwide and often lead to vision loss. Vitreous fluid abuts the retina, is accessible for sampling, and contains many proteins related to retinal disease. Therefore, analysis of vitreous is an important tool for studying retinal disease. Because it is rich in proteins and extracellular vesicles, mass spectrometry-based proteomics is an excellent method for vitreous analysis. Here, we discuss important variables to consider when performing vitreous proteomics via mass spectrometry.},
}
@article {pmid37326230,
year = {2023},
author = {Timtim, E and Weng, CY and Finn, AP},
title = {Safety of recent ophthalmic drugs and devices for wet macular degeneration.},
journal = {Current opinion in ophthalmology},
volume = {34},
number = {5},
pages = {363-368},
doi = {10.1097/ICU.0000000000000974},
pmid = {37326230},
issn = {1531-7021},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/adverse effects ; *Wet Macular Degeneration/drug therapy ; *Biosimilar Pharmaceuticals/therapeutic use ; Endothelial Growth Factors/therapeutic use ; Intravitreal Injections ; },
abstract = {PURPOSE OF REVIEW: With frequent antivascular endothelial growth factors (VEGF) injections well established as the standard of care in neovascular age-related macular degeneration (nAMD), focus has now shifted towards decreasing treatment burden without compromising safety and efficacy. This review summarizes clinical stage and recently approved drugs and devices for nAMD, with an emphasis paid to safety concerns and their implications for product adoption.<br><br>RECENT FINDINGS: Three strategies have emerged to decrease the treatment burden associated with the current standard of care: more durable intravitreal agents, sustained-release modalities and gene therapy. The appearance of biosimilars will further impact drug availability and cost. As patterns of adverse events emerge from clinical trial or postmarketing surveillance data, manufacturers have proactively responded by appointing independent review committees or issuing voluntary recalls. However, the example of one biosimilar approved outside of the USA and European Union demonstrates how early safety concerns, even when addressed by substantive data, can generate lingering uncertainty.<br><br>SUMMARY: As the number of promising new treatments in nAMD continues to grow, so too does the amount of data that providers must sift through. The perception of safety surrounding first movers in each new therapeutic area is sure to affect adoption of that modality more broadly.},
}
@article {pmid37324128,
year = {2023},
author = {Rondanelli, M and Gasparri, C and Riva, A and Petrangolini, G and Barrile, GC and Cavioni, A and Razza, C and Tartara, A and Perna, S},
title = {Diet and ideal food pyramid to prevent or support the treatment of diabetic retinopathy, age-related macular degeneration, and cataracts.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1168560},
pmid = {37324128},
issn = {2296-858X},
abstract = {Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective of this review is to assess the most recent research on the ideal dietary approach to prevent or support the treatment of DR, AMD, and cataracts, as well as to construct a food pyramid that makes it simple for people who are at risk of developing these pathologies to decide what to eat. The food pyramid presented here proposes what should be consumed every day: 3 portions of low glycemic index (GI) grains (for fiber and zinc content), 5 portions (each portion: ≥200 g/day) of fruits and vegetables (spinach, broccoli, zucchini cooked, green leafy vegetables, orange, kiwi, grapefruit for folic acid, vitamin C, and lutein/zeaxanthin content, at least ≥42 μg/day, are to be preferred), extra virgin olive (EVO) oil (almost 20 mg/day for vitamin E and polyphenols content), nuts or oil seeds (20-30 g/day, for zinc content, at least ≥15.8 mg/day); weekly: fish (4 portions, for omega-3 content and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) 0.35-1.4 g/day), white meat (3 portions for vitamin B12 content), legumes (2 portions for vegetal proteins), eggs (2 portions for lutein/zeaxanthin content), light cheeses (2 portions for vitamin B6 content), and almost 3-4 times/week microgreen and spices (saffron and curcumin). At the top of the pyramid, there are two pennants: one green, which indicates the need for personalized supplementation (if daily requirements cannot be met through diet, omega-3, and L-methylfolate supplementation), and one red, which indicates that certain foods are prohibited (salt and sugar). Finally, 3-4 times per week, 30-40 min of aerobic and resistance exercises are required.},
}
@article {pmid37322379,
year = {2023},
author = {Qian, X and Xian, S and Yifei, S and Wei, G and Liu, H and Xiaoming, X and Chu, C and Yilong, Y and Shuang, Y and Kai, M and Mei, C and Yi, Q},
title = {External validation of a deep learning detection system for glaucomatous optic neuropathy: a real-world multicentre study.},
journal = {Eye (London, England)},
volume = {37},
number = {18},
pages = {3813-3818},
pmid = {37322379},
issn = {1476-5454},
mesh = {Humans ; *Deep Learning ; Artificial Intelligence ; ROC Curve ; *Glaucoma/diagnosis/complications ; *Optic Nerve Diseases/diagnosis/complications ; },
abstract = {OBJECTIVES: To conduct an external validation of an automated artificial intelligence (AI) diagnostic system using fundus photographs from a real-life multicentre cohort.<br><br>METHODS: We designed external validation in multiple scenarios, consisting of 3049 images from Qilu Hospital of Shandong University in China (QHSDU, validation dataset 1), 7495 images from three other hospitals in China (validation dataset 2), and 516 images from high myopia (HM) population of QHSDU (validation dataset 3). The corresponding sensitivity, specificity and accuracy of this AI diagnostic system to identify glaucomatous optic neuropathy (GON) were calculated.<br><br>RESULTS: In validation datasets 1 and 2, the algorithm yielded accuracy of 93.18% and 91.40%, area under the receiver operating curves (AUC) of 95.17% and 96.64%, and significantly higher sensitivity of 91.75% and 91.41%, respectively, compared to manual graders. On the subsets complicated with retinal comorbidities, such as diabetic retinopathy or age-related macular degeneration, in validation datasets 1 and 2, the algorithm achieved accuracy of 87.54% and 93.81%, and AUC of 97.02% and 97.46%, respectively. In validation dataset 3, the algorithm achieved comparable accuracy of 81.98% and AUC of 87.49%, with a sensitivity of 83.61% and specificity of 81.76% on GON recognition specifically in the HM population.<br><br>CONCLUSIONS: With acceptable generalization capability across varying levels of image quality, different clinical centres, or certain retinal comorbidities, such as HM, the automatic AI diagnostic system had the potential to provide expert-level glaucoma detection.},
}
@article {pmid37320859,
year = {2023},
author = {Pakravan, P and Patel, V and Lai, J and Shaheen, A and Kalahasty, K and Reyes-Capo, DP and Chau, V and Rosenfeld, PJ and Haddock, LJ and Schwartz, SG and Smiddy, WE and Kovach, JL and Sridhar, J and Flynn, HW and Albini, TA and Yannuzzi, NA},
title = {INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {10},
pages = {1717-1722},
doi = {10.1097/IAE.0000000000003862},
pmid = {37320859},
issn = {1539-2864},
support = {P30EY014801/GF/NIH HHS/United States ; },
mesh = {Humans ; Angiogenesis Inhibitors ; Retrospective Studies ; Incidence ; *Uveitis/drug therapy ; Intravitreal Injections ; Inflammation/drug therapy ; *Uveal Diseases ; *Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center.<br><br>METHODS: A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed.<br><br>RESULTS: There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination.<br><br>CONCLUSION: Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.},
}
@article {pmid37318582,
year = {2023},
author = {Lee, K and Lee, S and Jung, S and Chin, HS},
title = {Analysis of ocular fluid in patients with ranibizumab-recalcitrant neovascular age-related macular degeneration who have serum anti-ranibizumab antibodies.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {12},
pages = {3581-3587},
pmid = {37318582},
issn = {1435-702X},
mesh = {Humans ; Ranibizumab ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To evaluate whether anti-drug antibodies (ADAs) are present in the ocular fluid of patients with ranibizumab-recalcitrant neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Two serum ADA-positive ranibizumab-recalcitrant patients and two serum ADA-negative controls were recruited from patients with nAMD treated with ranibizumab monotherapy. Recalcitrance was defined as persistent fluid after &#x2265;6 monthly ranibizumab injections. Serum and aqueous humor ADAs were detected by enzyme-linked immunosorbent assay and immunoprecipitation, respectively.<br><br>RESULTS: Two of 156 ranibizumab-treated patients were ADA-positive. The patients received six and 14 ranibizumab injections, respectively, up to 4 weeks prior to blood collection. The serum ADA concentration was estimated to be approximately 50,000 ng/mL. Neutralizing ADAs were confirmed in both samples. A specific band was detected by immunoprecipitation only in ADA-positive samples, consistent with the results of enzyme-linked immunosorbent assay. Based on an assessment of the degree of sensitivity of commercially available anti-ranibizumab antibodies, it was estimated that the immunoprecipitation method could detect ADA levels >30 ng. Nevertheless, ADAs were not detected in the aqueous humor of either the experimental or control group.<br><br>CONCLUSION: In the aqueous humor, ADAs are either not present or are present at a lower concentration than that which can be detected by immunoprecipitation. This presumably reflects the fact that blood ADA is the product of systemic circulation clearance through anterior elimination of intravitreal ranibizumab. Based on our results, ADAs do not return to the eye in sufficient quantities to interfere with the action of ranibizumab in the vitreous cavity.},
}
@article {pmid37317693,
year = {2023},
author = {Ahn, HS and Lee, Y and Kim, HM and Ju, S and Lee, S and Jeong, HG and Park, SJ and Park, KH and Lee, J and Lee, JY and Woo, SJ and Lee, C},
title = {Multiplexed plasma protein classifiers for the diagnosis of age-related macular degeneration.},
journal = {Clinical and translational medicine},
volume = {13},
number = {6},
pages = {e1307},
pmid = {37317693},
issn = {2001-1326},
mesh = {Humans ; *Blood Proteins ; *Macular Degeneration/diagnosis ; },
}
@article {pmid37316948,
year = {2023},
author = {Xu, W and Liu, X and Han, W and Wu, K and Zhao, M and Mei, T and Shang, B and Wu, J and Luo, J and Lai, Y and Yang, B and Zhuo, Y and Lu, L and Liu, Y and Tian, XL and Zhao, L},
title = {Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration.},
journal = {Cell communication and signaling : CCS},
volume = {21},
number = {1},
pages = {134},
pmid = {37316948},
issn = {1478-811X},
mesh = {Aged ; Humans ; Animals ; Mice ; *Retinal Degeneration ; Retinal Pigment Epithelium ; Signal Transduction ; Mitochondria ; Cell Nucleus ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD), characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptors, is the leading cause of irreversible vision impairment among the elderly. RPE senescence is an important contributor to AMD and has become a potential target for AMD therapy. HTRA1 is one of the most significant susceptibility genes in AMD, however, the correlation between HTRA1 and RPE senescence hasn't been investigated in the pathogenesis of AMD.<br><br>METHODS: Western blotting and immunohistochemistry were used to detect HTRA1 expression in WT and transgenic mice overexpressing human HTRA1 (hHTRA1-Tg mice). RT-qPCR was used to detect the SASP in hHTRA1-Tg mice and ARPE-19 cells infected with HTRA1. TEM, SA-&#x3b2;-gal was used to detect the mitochondria and senescence in RPE. Retinal degeneration of mice was investigated by fundus photography, FFA, SD-OCT and ERG. The RNA-Seq dataset of ARPE-19 cells treated with adv-HTRA1 versus adv-NC were analyzed. Mitochondrial respiration and glycolytic capacity in ARPE-19 cells were measured using OCR and ECAR. Hypoxia of ARPE-19 cells was detected using EF5 Hypoxia Detection Kit. KC7F2 was used to reduce the HIF1&#x3b1; expression both in vitro and in vivo.<br><br>RESULTS: In our study, we found that RPE senescence was facilitated in hHTRA1-Tg mice. And hHTRA1-Tg mice became more susceptible to NaIO3 in the development of oxidative stress-induced retinal degeneration. Similarly, overexpression of HTRA1 in ARPE-19 cells accelerated cellular senescence. Our RNA-seq revealed an overlap between HTRA1-induced differentially expressed genes associated with aging and those involved in mitochondrial function and hypoxia response in ARPE-19 cells. HTRA1 overexpression in ARPE-19 cells impaired mitochondrial function and augmented glycolytic capacity. Importantly, upregulation of HTRA1 remarkably activated HIF-1 signaling, shown as promoting HIF1&#x3b1; expression which mainly located in the nucleus. HIF1&#x3b1; translation inhibitor KC7F2 significantly prevented HTRA1-induced cellular senescence in ARPE-19 cells, as well as improved the visual function in hHTRA1-Tg mice treated with NaIO3.<br><br>CONCLUSIONS: Our study showed elevated HTRA1 contributes to the pathogenesis of AMD by promoting cellular senescence in RPE through damaging mitochondrial function and activating HIF-1 signaling. It also pointed out that inhibition of HIF-1 signaling might serve as a potential therapeutic strategy for AMD. Video Abstract.},
}
@article {pmid37315571,
year = {2023},
author = {Pfau, K and Jeffrey, BG and Cukras, CA},
title = {LOW-DOSE SUPPLEMENTATION WITH RETINOL IMPROVES RETINAL FUNCTION IN EYES WITH AGE-RELATED MACULAR DEGENERATION BUT WITHOUT RETICULAR PSEUDODRUSEN.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {9},
pages = {1462-1471},
doi = {10.1097/IAE.0000000000003840},
pmid = {37315571},
issn = {1539-2864},
mesh = {Humans ; Aged ; Aged, 80 and over ; Middle Aged ; Vitamin A ; Quality of Life ; *Macular Degeneration/diagnosis/drug therapy ; *Retinal Drusen/drug therapy ; Dietary Supplements ; Vision Disorders ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: The aim of this study was to determine the functional impact of oral vitamin A supplementation in patients with intermediate age-related macular degeneration with and without reticular pseudodrusen (RPD) demonstrating dysfunction in dark adaptation.<br><br>METHODS: Five patients with intermediate age-related macular degeneration and without RPD (AMD group; mean &#xb1; SD age 78.0 &#xb1; 4.7 years) and seven with RPD (RPD group; age 74.1 &#xb1; 11.2 years) were supplemented with 16,000 IU of vitamin A palmitate for 8 weeks. Assessment at baseline, 4, 8, and 12 weeks included scotopic thresholds, dark adaptation, best-corrected and low luminance visual acuities, and the low-luminance quality of life questionnaire.<br><br>RESULTS: In the linear mixed model, rod intercept time improved significantly in the AMD group (mean [95% CI] change -1.1 minutes [-1.8; -0.5] after 4 weeks (P < 0.001) and -2.2 min [-2.9 to -1.6] after 8 weeks of vitamin A supplementation (P < 0.001). The dark adaptation cone plateau also significantly improved (i.e., more sensitive cone threshold) at 4 and 8 weeks (P = 0.026 and P = 0.001). No other parameters improved in the AMD group, and there was no significant improvement in any parameter in the RPD group despite significantly elevated serum vitamin A levels measurable in both groups after supplementation (P = 0.024 and P = 0.013).<br><br>CONCLUSION: Supplementation with 16,000 IU vitamin A, a lower dose than used in previous studies, partially overcomes the pathophysiologic functional changes in AMD eyes. The lack of improvement in the RPD group may indicate structural impediments to increasing vitamin A availability in these patients and/or may reflect the higher variability observed in the functional parameters for this group.},
}
@article {pmid37314756,
year = {2023},
author = {Liu, K and Zou, J and Yuan, R and Fan, H and Hu, H and Cheng, Y and Liu, J and Zou, H and You, Z},
title = {Exploring the Effect of the Gut Microbiome on the Risk of Age-Related Macular Degeneration From the Perspective of Causality.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {7},
pages = {22},
pmid = {37314756},
issn = {1552-5783},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Macular Degeneration/genetics ; Retina ; Causality ; *Actinobacteria ; },
abstract = {PURPOSE: To explore the mechanisms relating the gut microbiome (GM) to age-related macular degeneration (AMD), as they remain unclear. GM taxa that appear to act within the gut-retina axis may affect the risk of AMD.<br><br>METHODS: Single-nucleotide polymorphisms (SNPs) of 196 GM taxa were obtained from the MiBioGen consortium, and a Mendelian randomization (MR) study was carried out to estimate the causality between GM taxa and AMD (defined as an endpoint based on ICD-9 and ICD-10). Using the data from the FinnGen consortium (6157 patients and 288,237 controls), we explored the GM taxa for causality and verified the results at the replication stage based on the MRC-IEU consortium (3553 cases and 147,089 controls). Inverse variance weighting (IVW) was the main method used to analyze causality, and the MR results were verified using heterogeneity tests and pleiotropy tests.<br><br>RESULTS: According to the MR results, order Rhodospirillales (P = 3.38 &#xd7; 10-2), family Victivallaceae (P = 3.14 &#xd7; 10-2), family Rikenellaceae (P = 3.58 &#xd7; 10-2), genus Slackia (P = 3.15 &#xd7; 10-2), genus Faecalibacterium (P = 3.01 &#xd7; 10-2), genus Bilophila (P = 1.11 &#xd7; 10-2), and genus Candidatus Soleaferrea (P = 2.45 &#xd7; 10-2) were suggestively associated with AMD. In the replication stage, only order Rhodospirillales (P = 0.03) passed validation. The heterogeneity (P > 0.05) and pleiotropy (P > 0.05) tests in two stages confirmed the robustness of the MR results.<br><br>CONCLUSIONS: We confirmed that order Rhodospirillales influenced the risk of AMD based on the gut-retina axis, providing new impetus for the development of the GM as an intervention to prevent the occurrence and development of AMD.},
}
@article {pmid37314523,
year = {2023},
author = {Kim, JH and Kim, JW and Kim, CG},
title = {Influence of lesion location on lesion reactivation after initial treatment in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {11},
pages = {3139-3148},
pmid = {37314523},
issn = {1435-702X},
abstract = {PURPOSE: We aim to evaluate the factors associated with the incidence of lesion reactivation after initial loading injections in patients with neovascular age-related macular degeneration (AMD).<br><br>METHODS: This retrospective study included patients diagnosed with treatment-na&#xef;ve neovascular AMD who received three loading injections of either ranibizumab or aflibercept. After the initial treatment, patients were followed up every 1-2 months during the first year and the follow-up interval was extended to 4 months during the second year. Retreatment was administered on an as-needed basis. The incidence and timing of lesion reactivation at 24 months after diagnosis were identified. In addition, Cox's proportional hazard model was used to evaluate the association of baseline factors with lesion reactivation. Lesion reactivation was defined re-accumulation of subretinal fluid/intraretinal fluid or the development of subretinal/intraretinal hemorrhage.<br><br>RESULTS: A total of 284 patients (173 men and 111 women) were included in the study. The mean age of the patients was 70.5 &#xb1; 8.8 years. During the 24-month follow-up period, lesion reactivation was observed in 216 eyes (76.1%) at a mean of 8.2 &#xb1; 4.4 months after diagnosis. The incidence of lesion reactivation was 62.5% in extrafoveal macular neovascularization (MNV), 75.0% in juxtafoveal MNV, and 79.5% in subfoveal MNV. The extrafoveal MNV showed significantly lower incidence of lesion reactivation than subfoveal MNV (P = 0.041, hazard ratio = 0.64).<br><br>CONCLUSIONS: Extrafoveal MNVs showed a lower incidence of lesion reactivation after initial treatment than subfoveal MNVs. This result should be considered when interpreting the results of clinical trials with different eligibility criteria regarding lesion location.},
}
@article {pmid37314061,
year = {2023},
author = {Tzoumas, N and Riding, G and Williams, MA and Steel, DH},
title = {Complement inhibitors for age-related macular degeneration.},
journal = {The Cochrane database of systematic reviews},
volume = {6},
number = {6},
pages = {CD009300},
pmid = {37314061},
issn = {1469-493X},
mesh = {Humans ; Administration, Intravenous ; Complement Inactivating Agents/adverse effects ; *Endophthalmitis ; *Geographic Atrophy/drug therapy ; *Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common eye disease and leading cause of sight loss worldwide. Despite its high prevalence and increasing incidence as populations age, AMD remains incurable and there are no treatments for most patients. Mounting genetic and molecular evidence implicates complement system overactivity as a key driver of AMD development and progression. The last decade has seen the development of several novel therapeutics targeting complement in the eye for the treatment of AMD. This review update encompasses the results of the first randomised controlled trials in this field.<br><br>OBJECTIVES: To assess the effects and safety of complement inhibitors in the prevention or treatment of AMD.<br><br>SEARCH METHODS: We searched CENTRAL on the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, ISRCTN registry, ClinicalTrials.gov, and the WHO ICTRP to 29 June 2022 with no language restrictions. We also contacted companies running clinical trials for unpublished data.<br><br>SELECTION CRITERIA: We included randomised controlled trials (RCTs) with parallel groups and comparator arms that studied complement inhibition for advanced AMD prevention/treatment.<br><br>DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results and resolved discrepancies through discussion. Outcome measures evaluated at one year included change in best-corrected visual acuity (BCVA), untransformed and square root-transformed geographic atrophy (GA) lesion size progression, development of macular neovascularisation (MNV) or exudative AMD, development of endophthalmitis, loss of &#x2265; 15 letters of BCVA, change in low luminance visual acuity, and change in quality of life. We assessed risk of bias and evidence certainty using Cochrane risk of bias and GRADE tools.<br><br>MAIN RESULTS: Ten RCTs with 4052 participants and eyes with GA were included. Nine evaluated intravitreal (IVT) administrations against sham, and one investigated an intravenous agent against placebo. Seven studies excluded patients with prior MNV in the non-study eye, whereas the three pegcetacoplan studies did not. The risk of bias in the included studies was low overall. We also synthesised results of two intravitreal agents (lampalizumab, pegcetacoplan) at monthly and every-other-month (EOM) dosing intervals. Efficacy and safety of IVT lampalizumab versus sham for GA For 1932 participants in three studies, lampalizumab did not meaningfully change BCVA given monthly (+1.03 letters, 95% confidence interval (CI) -0.19 to 2.25) or EOM (+0.22 letters, 95% CI -1.00 to 1.44) (high-certainty evidence). For 1920 participants, lampalizumab did not meaningfully change GA lesion growth given monthly (+0.07 mm&#xb2;, 95% CI -0.09 to 0.23; moderate-certainty due to imprecision) or EOM (+0.07 mm&#xb2;, 95% CI -0.05 to 0.19; high-certainty). For 2000 participants, lampalizumab may have also increased MNV risk given monthly (RR 1.77, 95% CI 0.73 to 4.30) and EOM (RR 1.70, 95% CI 0.67 to 4.28), based on low-certainty evidence. The incidence of endophthalmitis in patients treated with monthly and EOM lampalizumab was 4 per 1000 (0 to 87) and 3 per 1000 (0 to 62), respectively, based on moderate-certainty evidence. Efficacy and safety of IVT pegcetacoplan versus sham for GA For 242 participants in one study, pegcetacoplan probably did not meaningfully change BCVA given monthly (+1.05 letters, 95% CI -2.71 to 4.81) or EOM (-1.42 letters, 95% CI -5.25 to 2.41), as supported by moderate-certainty evidence. In contrast, for 1208 participants across three studies, pegcetacoplan meaningfully reduced GA lesion growth when given monthly (-0.38 mm&#xb2;, 95% CI -0.57 to -0.19) and EOM (-0.29 mm&#xb2;, 95% CI -0.44 to -0.13), with high certainty. These reductions correspond to 19.2% and 14.8% versus sham, respectively. A post hoc analysis showed possibly greater benefits in 446 participants with extrafoveal GA given monthly (-0.67 mm&#xb2;, 95% CI -0.98 to -0.36) and EOM (-0.60 mm&#xb2;, 95% CI -0.91 to -0.30), representing 26.1% and 23.3% reductions, respectively. However, we did not have data on subfoveal GA growth to undertake a formal subgroup analysis. In 1502 participants, there is low-certainty evidence that pegcetacoplan may have increased MNV risk when given monthly (RR 4.47, 95% CI 0.41 to 48.98) or EOM (RR 2.29, 95% CI 0.46 to 11.35). The incidence of endophthalmitis in patients treated with monthly and EOM pegcetacoplan was 6 per 1000 (1 to 53) and 8 per 1000 (1 to 70) respectively, based on moderate-certainty evidence. Efficacy and safety of IVT avacincaptad pegol versus sham for GA In a study of 260 participants with extrafoveal or juxtafoveal GA, monthly avacincaptad pegol probably did not result in a clinically meaningful change in BCVA at 2 mg (+1.39 letters, 95% CI -5.89 to 8.67) or 4 mg (-0.28 letters, 95% CI -8.74 to 8.18), based on moderate-certainty evidence. Despite this, the drug was still found to have probably reduced GA lesion growth, with estimates of 30.5% reduction at 2 mg (-0.70 mm&#xb2;, 95% CI -1.99 to 0.59) and 25.6% reduction at 4 mg (-0.71 mm&#xb2;, 95% CI -1.92 to 0.51), based on moderate-certainty evidence. Avacincaptad pegol may have also increased the risk of developing MNV (RR 3.13, 95% CI 0.93 to 10.55), although this evidence is of low certainty. There were no cases of endophthalmitis reported in this study.<br><br>AUTHORS' CONCLUSIONS: Despite confirmation of the negative findings of intravitreal lampalizumab across all endpoints, local complement inhibition with intravitreal pegcetacoplan meaningfully reduces GA lesion growth relative to sham at one year. Inhibition of complement C5 with intravitreal avacincaptad pegol is also an emerging therapy with probable benefits on anatomical endpoints in the extrafoveal or juxtafoveal GA population. However, there is currently no evidence that complement inhibition with any agent improves functional endpoints in advanced AMD; further results from the phase 3 studies of pegcetacoplan and avacincaptad pegol are eagerly awaited. Progression to MNV or exudative AMD is a possible emergent adverse event of complement inhibition, requiring careful consideration should these agents be used clinically. Intravitreal administration of complement inhibitors is probably associated with a small risk of endophthalmitis, which may be higher than that of other intravitreal therapies. Further research is likely to have an important impact on our confidence in the estimates of adverse effects and may change these. The optimal dosing regimens, treatment duration, and cost-effectiveness of such therapies are yet to be established.},
}
@article {pmid37312852,
year = {2023},
author = {Lee, JJ and Hu, Z and Wang, YA and Nath, D and Liang, W and Cui, Y and Ma, JX and Duerfeldt, AS},
title = {Design, Synthesis, and Structure-Activity Relationships of Biaryl Anilines as Subtype-Selective PPAR-alpha Agonists.},
journal = {ACS medicinal chemistry letters},
volume = {14},
number = {6},
pages = {766-776},
pmid = {37312852},
issn = {1948-5875},
support = {R01 EY028949/EY/NEI NIH HHS/United States ; R01 EY030472/EY/NEI NIH HHS/United States ; R01 EY033330/EY/NEI NIH HHS/United States ; },
abstract = {The role of peroxisome proliferator-activated receptor alpha (PPARα) in retinal biology is clarifying, and evidence demonstrates that novel PPARα agonists hold promising therapeutic utility for diseases like diabetic retinopathy and age-related macular degeneration. Herein, we disclose the design and initial structure-activity relationships for a new biaryl aniline PPARα agonistic chemotype. Notably, this series exhibits subtype selectivity for PPARα over other isoforms, a phenomenon postulated to be due to the unique benzoic acid headgroup. This biphenyl aniline series is sensitive to B-ring functionalization but allows isosteric replacement, and provides an opportunity for C-ring extension. From this series, 3g, 6j, and 6d were identified as leads with <90 nM potency in a cell-based luciferase assay cell and exhibited efficacy in various disease-relevant cell contexts, thereby setting the stage for further characterization in more advanced in vitro and in vivo models.},
}
@article {pmid37312562,
year = {2024},
author = {Semenova, Y and Bjørklund, G},
title = {Antioxidants and neurodegenerative eye disease.},
journal = {Critical reviews in food science and nutrition},
volume = {64},
number = {26},
pages = {9672-9690},
doi = {10.1080/10408398.2023.2215865},
pmid = {37312562},
issn = {1549-7852},
mesh = {*Antioxidants/pharmacology ; Humans ; *Oxidative Stress/drug effects ; *Dietary Supplements ; *Macular Degeneration/prevention &amp; control ; *Neurodegenerative Diseases ; *Glaucoma ; Eye Diseases ; Reactive Oxygen Species/metabolism ; Quality of Life ; },
abstract = {Neurodegenerative ocular disorders mostly develop with aging and present great complications in the quality of life. Glaucoma and age-related macular degeneration (ARMD) rank as the third and fourth leading causes of blindness and low vision. Oxidative stress is one factor in the pathogenesis of neurodegenerative eye disease. In addition, ocular ischemia and neuroinflammation play an important role. It can be hypothesized that the influence of antioxidants through diet or oral supplementation can counteract the harmful effects of reactive oxygen species accumulated secondary to oxidative stress, ischemia, and inflammation. A range of studies has been published over the past decades focusing on the possible adjuvant effect of antioxidants in ARMD, while there were fewer reports on the potential role of antioxidants in glaucoma. Although certain reports demonstrated positive results, others were discouraging. As there is a controversy between the studies favoring and disfavoring supplementation with different types of antioxidants, it is important to revise the existing evidence on the role of antioxidants in neurodegenerative ocular disorders with a special focus on glaucoma and ARMD.},
}
@article {pmid37311835,
year = {2023},
author = {Pawloff, M and Gerendas, BS and Deak, G and Bogunovic, H and Gruber, A and Schmidt-Erfurth, U},
title = {Performance of retinal fluid monitoring in OCT imaging by automated deep learning versus human expert grading in neovascular AMD.},
journal = {Eye (London, England)},
volume = {37},
number = {18},
pages = {3793-3800},
pmid = {37311835},
issn = {1476-5454},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Tomography, Optical Coherence/methods ; *Deep Learning ; Reproducibility of Results ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; Subretinal Fluid/diagnostic imaging ; },
abstract = {PURPOSE: To evaluate the reliability of automated fluid detection in identifying retinal fluid activity in OCT scans of patients treated with anti-VEGF therapy for neovascular age-related macular degeneration by correlating human expert and automated measurements with central retinal subfield thickness (CSFT) and fluid volume values.<br><br>METHODS: We utilized an automated deep learning approach to quantify macular fluid in SD-OCT volumes (Cirrus, Spectralis, Topcon) from patients of HAWK and HARRIER Studies. Three-dimensional volumes for IRF and SRF were measured at baseline and under therapy in the central millimeter and compared to fluid gradings, CSFT and foveal centerpoint thickness (CPT) values measured by the Vienna Reading Center.<br><br>RESULTS: 41.906 SD-OCT volume scans were included into the analysis. Concordance between human expert grading and automated algorithm performance reached AUC values of 0.93/0.85 for IRF and 0.87 for SRF in HARRIER/HAWK in the central millimeter. IRF volumes showed a moderate correlation with CSFT at baseline (HAWK: r&#x2009;=&#x2009;0.54; HARRIER: r&#x2009;=&#x2009;0.62) and weaker correlation under therapy (HAWK: r&#x2009;=&#x2009;0.44; HARRIER: r&#x2009;=&#x2009;0.34). SRF and CSFT correlations were low at baseline (HAWK: r&#x2009;=&#x2009;0.29; HARRIER: r&#x2009;=&#x2009;0.22) and under therapy (HAWK: r&#x2009;=&#x2009;0.38; HARRIER: r&#x2009;=&#x2009;0.45). The residual standard error (IRF: 75.90&#x2009;&#xb5;m; SRF: 95.26&#x2009;&#xb5;m) and marginal residual standard deviations (IRF: 46.35&#x2009;&#xb5;m; SRF: 44.19&#x2009;&#xb5;m) of fluid volume were high compared to the range of CSFT values.<br><br>CONCLUSION: Deep learning-based segmentation of retinal fluid performs reliably on OCT images. CSFT values are weak indicators for fluid activity in nAMD. Automated quantification of fluid types, highlight the potential of deep learning-based approaches to objectively monitor anti-VEGF therapy.},
}
@article {pmid37311794,
year = {2023},
author = {El-Den, NN and Naglah, A and Elsharkawy, M and Ghazal, M and Alghamdi, NS and Sandhu, H and Mahdi, H and El-Baz, A},
title = {Scale-adaptive model for detection and grading of age-related macular degeneration from color retinal fundus images.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {9590},
pmid = {37311794},
issn = {2045-2322},
mesh = {Humans ; Fluorescein Angiography ; Fundus Oculi ; *Macula Lutea ; Retina/diagnostic imaging ; *Wet Macular Degeneration ; },
abstract = {Age-related Macular Degeneration (AMD), a retinal disease that affects the macula, can be caused by aging abnormalities in number of different cells and tissues in the retina, retinal pigment epithelium, and choroid, leading to vision loss. An advanced form of AMD, called exudative or wet AMD, is characterized by the ingrowth of abnormal blood vessels beneath or into the macula itself. The diagnosis is confirmed by either fundus auto-fluorescence imaging or optical coherence tomography (OCT) supplemented by fluorescein angiography or OCT angiography without dye. Fluorescein angiography, the gold standard diagnostic procedure for AMD, involves invasive injections of fluorescent dye to highlight retinal vasculature. Meanwhile, patients can be exposed to life-threatening allergic reactions and other risks. This study proposes a scale-adaptive auto-encoder-based model integrated with a deep learning model that can detect AMD early by automatically analyzing the texture patterns in color fundus imaging and correlating them to the vasculature activity in the retina. Moreover, the proposed model can automatically distinguish between AMD grades assisting in early diagnosis and thus allowing for earlier treatment of the patient's condition, slowing the disease and minimizing its severity. Our model features two main blocks, the first is an auto-encoder-based network for scale adaption, and the second is a convolutional neural network (CNN) classification network. Based on a conducted set of experiments, the proposed model achieves higher diagnostic accuracy compared to other models with accuracy, sensitivity, and specificity that reach 96.2%, 96.2%, and 99%, respectively.},
}
@article {pmid37310683,
year = {2023},
author = {Zubricky, R and McCoy, J and Donkor, R and Miller, DG and Sonbolian, N and Heaney, A and Bilano, V and Karcher, H and Coney, JM},
title = {Real-World Frequency and Management of Ocular Adverse Events in Eyes with Neovascular Age-Related Macular Degeneration Treated with Brolucizumab.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {5},
pages = {2397-2408},
pmid = {37310683},
issn = {2193-8245},
abstract = {INTRODUCTION: Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice.<br><br>METHODS: Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with&#x2009;&#x2265;&#x2009;1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics.<br><br>RESULTS: Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3&#xa0;months and 4/22 (18%) within 3-6&#xa0;months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4-34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of&#x2009;&#x2265;&#x2009;30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI&#x2009;+&#x2009;RV, 1 with IOI&#x2009;+&#x2009;RV&#x2009;+&#x2009;RO) developed moderate vision loss of&#x2009;&#x2265;&#x2009;15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was -6.8 (-19.9, -0.0) letters. Taking the best VA at either 3 or 6&#xa0;months after AE resolution (or stability for occlusive events), VA decreased by&#x2009;&#x2265;&#x2009;5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (<&#x2009;5-letter loss) in 18 (82%) eyes.<br><br>CONCLUSIONS: In this real-world study, most IOI-related AEs occurred early after brolucizumab treatment initiation. With appropriate monitoring and management of IOI-related AEs, vision loss associated with brolucizumab may be limited.},
}
@article {pmid37309709,
year = {2023},
author = {Heilenbach, N and Hu, G and Lamrani, R and Prasad, J and Ogunsola, T and Iskander, M and Elgin, CY and McGowan, R and Vieira, D and Al-Aswad, LA},
title = {Environmental influences on ophthalmic conditions: A scoping review.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {51},
number = {6},
pages = {516-545},
doi = {10.1111/ceo.14262},
pmid = {37309709},
issn = {1442-9071},
mesh = {Humans ; *Air Pollution/adverse effects/analysis ; *Air Pollutants/adverse effects/analysis ; Sulfur Dioxide/adverse effects/analysis ; *Ozone/adverse effects/analysis ; Particulate Matter/adverse effects/analysis ; Environmental Exposure/adverse effects/analysis ; },
abstract = {BACKGROUND: Environmental factors have been implicated in various eye pathologies. The purpose of this review is to synthesise the published research on environmental effects on eye disease.<br><br>METHODS: Four databases were searched for terms relating to environmental exposures and ophthalmic disease. Titles and abstracts were screened followed by full-text review. Data was extracted from 118 included studies. Quality assessment was conducted for each study.<br><br>RESULTS: Air pollutants, including nitrogen dioxide, nitrites, sulphur dioxide, particulate matter, carbon monoxide, ozone and hydrocarbons are associated with ocular conditions ranging from corneal damage to various retinopathies, including central retinal artery occlusion. Certain chemicals and metals, such as cadmium, are associated with increased risk of age-related macular degeneration. Climate factors, such as sun exposure, have been associated with the development of cataracts. Living in rural areas was associated with various age-related eye diseases whereas people living in urban settings had higher risk for dry eye disease and uveitis.<br><br>CONCLUSION: Environmental exposures in every domain are associated with various ophthalmic conditions. These findings underscore the importance of continued research on the interplay between the environment and eye health.},
}
@article {pmid37308902,
year = {2023},
author = {Zhong, P and Tan, S and Zhu, Z and Bulloch, G and Long, E and Huang, W and He, M and Wang, W},
title = {Metabolomic phenotyping of obesity for profiling cardiovascular and ocular diseases.},
journal = {Journal of translational medicine},
volume = {21},
number = {1},
pages = {384},
pmid = {37308902},
issn = {1479-5876},
mesh = {Humans ; *Cardiovascular System ; *Heart Failure ; Metabolomics ; Obesity ; *Myocardial Infarction ; },
abstract = {BACKGROUND: We aimed to evaluate the impacts of metabolomic body mass index (metBMI) phenotypes on the risks of cardiovascular and ocular diseases outcomes.<br><br>METHODS: This study included cohorts in UK and Guangzhou, China.&#xa0;By leveraging the serum metabolome and BMI data from UK Biobank, this study developed and validated a metBMI prediction model using a ridge regression model among 89,830 participants based on 249 metabolites. Five obesity phenotypes were obtained by metBMI and actual BMI (actBMI): normal weight (NW, metBMI of 18.5-24.9&#xa0;kg/m[2]), overweight (OW, metBMI of 25-29.9&#xa0;kg/m[2]), obesity (OB, metBMI&#x2009;&#x2265;&#x2009;30&#xa0;kg/m[2]), overestimated (OE, metBMI-actBMI&#x2009;>&#x2009;5&#xa0;kg/m[2]), and underestimated (UE, metBMI-actBMI&#x2009;<&#x2009;-&#x2009;5&#xa0;kg/m[2]). Additional participants from the Guangzhou Diabetes Eye Study (GDES) were included for validating the hypothesis.&#xa0;Outcomes included all-cause and cardiovascular (CVD)-cause mortality, as well as incident CVD (coronary heart disease, heart failure, myocardial infarction [MI], and stroke) and&#xa0;age-related eye diseases (age-related macular degeneration [AMD], cataracts, glaucoma, and diabetic retinopathy [DR]).<br><br>RESULTS: In the UKB, although OE group had lower actBMI than NW group, the OE group had a significantly higher risk of all-cause mortality than those in NW prediction group (HR, 1.68; 95% CI 1.16-2.43). Similarly, the OE group had a 1.7-3.6-fold higher risk than their NW counterparts for cardiovascular mortality, heart failure, myocardial infarction, and coronary heart disease (all P&#x2009;<&#x2009;0.05). In addition, risk of age-related macular denegation (HR, 1.96; 95% CI 1.02-3.77) was significantly higher in OE group. In the contrast, UE and OB groups showed similar risks of mortality and of cardiovascular and age-related eye diseases (all P&#x2009;>&#x2009;0.05), though the UE group had significantly higher actBMI than OB group. In the GDES cohort, we further confirmed the potential of metabolic BMI (metBMI) fingerprints for risk stratification of cardiovascular diseases using a different metabolomic approach.<br><br>CONCLUSIONS: Gaps of metBMI and actBMI identified novel metabolic subtypes, which exhibit distinctive cardiovascular and ocular risk profiles. The groups carrying obesity-related metabolites were at higher risk of mortality and morbidity than those with normal health metabolites. Metabolomics allowed for leveraging the future of diagnosis and management of 'healthily obese' and 'unhealthily lean' individuals.},
}
@article {pmid37306515,
year = {2023},
author = {Korva-Gurung, I and Kubin, AM and Ohtonen, P and Hautala, N},
title = {Incidence and prevalence of neovascular age-related macular degeneration: 15-year epidemiological study in a population-based cohort in Finland.},
journal = {Annals of medicine},
volume = {55},
number = {1},
pages = {2222545},
pmid = {37306515},
issn = {1365-2060},
mesh = {Humans ; Female ; Aged ; Male ; Finland ; *Angiogenesis Inhibitors ; Incidence ; Prevalence ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Epidemiologic Studies ; },
abstract = {BACKGROUND/OBJECTIVES: Neovascular age-related macular degeneration (nAMD) is a common cause for visual impairment in the ageing population. An increasing number of nAMD patients causes significant health burden, although intravitreal anti-VEGF agents have revolutionized nAMD treatment during the past 15 years. We aimed to define incidence and prevalence of nAMD in different age-categories in the anti-VEGF era and to estimate the number of the individuals over 75 years of age in 2050.<br><br>PATIENTS AND METHODS: We conducted an epidemiological study of the nAMD cohort (n&#x2009;=&#x2009;2121) in a Finnish population of 410,000 inhabitants. Demographic and clinical data were gathered from Oulu University Hospital's database during 2006-2020. The incidence and prevalence rates were calculated using population data from national registers. The three-year moving average of incidence of nAMD per 100,000 person years was estimated. Prevalence figures were calculated per 100,000 age-specific inhabitants.<br><br>RESULTS: The average age at the diagnosis of nAMD was 788 years, and 62% of the patients were women. The incidence of nAMD was 71 (95% CI 55-90) and 102 (95% CI 88-118) per 100,000 person years in 2006 and 2020, respectively. During 2006-2020, 1.2- and 2.4-fold increases in nAMD incidence were noted in 75-84 and in 85-96 age groups, respectively. In the oldest 75-84 and 85-96 age categories the nAMD prevalence was 2865/100,000 (3%, 95% CI 2665-3079) and 2620/100,000 (3%, 95% CI 2323-2956), respectively. The proportion of the inhabitants >75&#x2009;years old is estimated to increase from 10% in 2020 to 17% by 2050.<br><br>CONCLUSIONS: Our results indicate constant 1.2- and 2.4-fold increases in nAMD incidence during the past 15&#x2009;years in age groups of 75-84 and 85-96&#x2009;years, respectively, and 3% prevalence of nAMD in 2020. An almost two-fold increase in the ageing population by the year 2050 may also predict the trends in nAMD.KEY MESSAGESThe results of the current population-based study indicate 1.2- and 2.4-fold increases in the incidence of neovascular AMD (nAMD) during the last 15 years in the Finnish population aged 75-84 and 85-96 years and 3% prevalence of nAMD in 2020.An almost two-fold increase in the number of individuals over 75 years of age by the year 2050 is estimated, which may also predict the trends in nAMD.Intravitreal anti-vascular endothelial growth factor (anti-VEGF)- agents have revolutionized the treatment and prognosis of nAMD. Timely recognition and referral of nAMD patients to ophthalmologist can ensure vision-related functionality especially among the ageing population.},
}
@article {pmid37306429,
year = {2023},
author = {von der Emde, L and Mallwitz, M and Holz, FG and Sloan, KR and Ach, T},
title = {A Workflow to Quantitatively Determine Age-Related Macular Degeneration Lesion-Specific Variations in Fundus Autofluorescence.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {195},
pages = {},
doi = {10.3791/65238},
pmid = {37306429},
issn = {1940-087X},
support = {R01 EY027948/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Fundus Oculi ; Workflow ; *Macular Degeneration ; Retina ; *Optic Disk ; },
abstract = {Fundus autofluorescence (FAF) imaging allows the noninvasive mapping of intrinsic fluorophores of the ocular fundus, particularly the retinal pigment epithelium (RPE), now quantifiable with the advent of confocal scanning laser ophthalmoscopy-based quantitative autofluorescence (QAF). QAF has been shown to be generally decreased at the posterior pole in age-related macular degeneration (AMD). The relationship between QAF and various AMD lesions (drusen, subretinal drusenoid deposits) is still unclear. This paper describes a workflow to determine lesion-specific QAF in AMD. A multimodal in vivo imaging approach is used, including but not limited to spectral domain optical coherence tomography (SD-OCT) macular volume scanning and QAF. Using customized FIJI plug-ins, the corresponding QAF image is aligned with the near-infrared image from the SD-OCT scan (characteristic landmarks; i.e., vessel bifurcations). The foveola and the edge of the optic nerve head are marked in the OCT images (and transferred to the registered QAF image) for accurate positioning of the analysis grids. AMD-specific lesions can then be marked on individual OCT BScans or the QAF image itself. Normative QAF maps are created to account for the varying mean and standard deviation of QAF values throughout the fundus (QAF images from a representative AMD group were averaged to build normative standard retinal QAF AMD maps). The plug-ins record the X and Y coordinates, z-score (a numerical measurement that describes the QAF value in relation to the mean of AF maps in terms of standard deviation from the mean), mean intensity value, standard deviation, and number of pixels marked. The tools also determine z-scores from the border zone of marked lesions. This workflow and the analysis tools will improve the understanding of the pathophysiology and clinical AF image interpretation in AMD.},
}
@article {pmid37306417,
year = {2023},
author = {Messinger, JD and Brinkmann, M and Kimble, JA and Berlin, A and Freund, KB and Grossman, GH and Ach, T and Curcio, CA},
title = {Ex Vivo OCT-Based Multimodal Imaging of Human Donor Eyes for Research into Age-Related Macular Degeneration.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {195},
pages = {},
pmid = {37306417},
issn = {1940-087X},
support = {R01 EY015520/EY/NEI NIH HHS/United States ; R01 EY006109/EY/NEI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY031209/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; U54 EY032442/EY/NEI NIH HHS/United States ; R01 EY006012/EY/NEI NIH HHS/United States ; R01 EY030192/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Aged, 80 and over ; *Tomography, Optical Coherence ; *Macular Degeneration ; Retina ; Multimodal Imaging ; },
abstract = {A progression sequence for age-related macular degeneration (AMD) learned from optical coherence tomography (OCT)-based multimodal (MMI) clinical imaging could add prognostic value to laboratory findings. In this work, ex vivo OCT and MMI were applied to human donor eyes prior to retinal tissue sectioning. The eyes were recovered from non-diabetic white donors aged ≥80 years old, with a death-to-preservation time (DtoP) of ≤6 h. The globes were recovered on-site, scored with an 18 mm trephine to facilitate cornea removal, and immersed in buffered 4% paraformaldehyde. Color fundus images were acquired after anterior segment removal with a dissecting scope and an SLR camera using trans-, epi-, and flash illumination at three magnifications. The globes were placed in a buffer within a custom-designed chamber with a 60 diopter lens. They were imaged with spectral domain OCT (30° macula cube, 30 µm spacing, averaging = 25), near-infrared reflectance, 488 nm autofluorescence, and 787 nm autofluorescence. The AMD eyes showed a change in the retinal pigment epithelium (RPE), with drusen or subretinal drusenoid deposits (SDDs), with or without neovascularization, and without evidence of other causes. Between June 2016 and September 2017, 94 right eyes and 90 left eyes were recovered (DtoP: 3.9 ± 1.0 h). Of the 184 eyes, 40.2% had AMD, including early intermediate (22.8%), atrophic (7.6%), and neovascular (9.8%) AMD, and 39.7% had unremarkable maculas. Drusen, SDDs, hyper-reflective foci, atrophy, and fibrovascular scars were identified using OCT. Artifacts included tissue opacification, detachments (bacillary, retinal, RPE, choroidal), foveal cystic change, an undulating RPE, and mechanical damage. To guide the cryo-sectioning, OCT volumes were used to find the fovea and optic nerve head landmarks and specific pathologies. The ex vivo volumes were registered with the in vivo volumes by selecting the reference function for eye tracking. The ex vivo visibility of the pathology seen in vivo depends on the preservation quality. Within 16 months, 75 rapid DtoP donor eyes at all stages of AMD were recovered and staged using clinical MMI methods.},
}
@article {pmid37304044,
year = {2023},
author = {Edmonds, R and Steffen, V and Honigberg, LA and Chang, MC},
title = {The Role of the Complement Pathway in Clinical Progression of Geographic Atrophy: Analysis of the Phase III Chroma and Spectri Trials.},
journal = {Ophthalmology science},
volume = {3},
number = {4},
pages = {100301},
pmid = {37304044},
issn = {2666-9145},
abstract = {PURPOSE: To investigate the relationship between complement pathway activities and progression of geographic atrophy (GA) secondary to age-related macular degeneration in samples collected from patients enrolled in the Chroma and Spectri trials.<br><br>DESIGN: Chroma and Spectri were phase III, double-masked, and sham-controlled, 96-week trials.<br><br>PARTICIPANTS: Aqueous humor (AH) samples collected at baseline and week 24 visits from 81 patients with bilateral GA across all 3 treatment groups (intravitreal lampalizumab 10 mg every 6 weeks, every 4 weeks, or corresponding sham procedures) were tested, along with patient-matched plasma samples collected at baseline.<br><br>METHODS: Antibody capture assays using the Simoa platform were used to measure the levels of complement factor B, the Bb fragment of complement factor B, intact complement component 3 (C3), processed C3, intact complement C4, and processed C4. Complement factor D levels were measured using enzyme-linked immunosorbent assay.<br><br>MAIN OUTCOME MEASURES: Correlations of complement levels and activities (i.e., processed:intact ratio of complement component) in AH and plasma with baseline GA lesion size and growth rate.<br><br>RESULTS: In baseline AH, there were strong correlations (Spearman's rho &#x2265; 0.80) between intact complement proteins, between processed complement proteins, and between linked processed and intact complement proteins; weak correlations (rho &#x2264; 0.24) were found between complement pathway activities. There were no strong correlations between complement protein levels and activities measured in AH and plasma at baseline (rho &#x2264; 0.37). Baseline complement levels and activities in AH and plasma did not correlate with baseline GA lesion size or change from baseline in GA lesion area at week 48 (i.e., annualized growth rate). There were no strong correlations between changes in complement levels/activities in the AH from baseline to week 24 and annualized GA lesion growth rate. Genotype analysis did not reveal a meaningful correlation between complement-related, age-related macular degeneration risk single-nucleotide polymorphisms and complement levels and activities.<br><br>CONCLUSIONS: Complement levels or activities in AH and plasma did not correlate with GA lesion size or growth rate. This suggests that local complement activation as measured in AH does not appear to be related to GA lesion progression.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37304043,
year = {2023},
author = {Maunz, A and Barras, L and Kawczynski, MG and Dai, J and Lee, AY and Spaide, RF and Sahni, J and Ferrara, D},
title = {Machine Learning to Predict Response to Ranibizumab in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {3},
number = {4},
pages = {100319},
pmid = {37304043},
issn = {2666-9145},
support = {K23 EY029246/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) shows variable treatment response to intravitreal anti-VEGF. This analysis compared the potential of different artificial intelligence (AI)-based machine learning models using OCT and clinical variables to accurately predict at baseline the best-corrected visual acuity (BCVA) at 9 months in response to ranibizumab in patients with nAMD.<br><br>DESIGN: Retrospective analysis.<br><br>PARTICIPANTS: Baseline and imaging data from patients with subfoveal choroidal neovascularization secondary to age-related macular dengeration.<br><br>METHODS: Baseline data from 502 study eyes from the HARBOR (NCT00891735) prospective clinical trial (monthly ranibizumab 0.5 and 2.0 mg arms) were pooled; 432 baseline OCT volume scans were included in the analysis. Seven models, based on baseline quantitative OCT features (Least absolute shrinkage and selection operator [Lasso] OCT minimum [min], Lasso OCT 1 standard error [SE]); on quantitative OCT features and clinical variables at baseline (Lasso min, Lasso 1SE, CatBoost, RF [random forest]); or on baseline OCT images only (deep learning [DL] model), were systematically compared with a benchmark linear model of baseline age and BCVA. Quantitative OCT features were derived by a DL segmentation model on the volume images, including retinal layer volumes and thicknesses, and retinal fluid biomarkers, including statistics on fluid volume and distribution.<br><br>MAIN OUTCOME MEASURES: Prognostic ability of the models was evaluated using coefficient of determination (R[2]) and median absolute error (MAE; letters).<br><br>RESULTS: In the first cross-validation split, mean R[2] (MAE) of the Lasso min, Lasso 1SE, CatBoost, and RF models was 0.46 (7.87), 0.42 (8.43), 0.45 (7.75), and 0.43 (7.60), respectively. These models ranked higher than or similar to the benchmark model (mean R[2], 0.41; mean MAE, 8.20 letters) and better than OCT-only models (mean R[2]: Lasso OCT min, 0.20; Lasso OCT 1SE, 0.16; DL, 0.34). The Lasso min model was selected for detailed analysis; mean R[2] (MAE) of the Lasso min and benchmark models for 1000 repeated cross-validation splits were 0.46 (7.7) and 0.42 (8.0), respectively.<br><br>CONCLUSIONS: Machine learning models based on AI-segmented OCT features and clinical variables at baseline may predict future response to ranibizumab treatment in patients with nAMD. However, further developments will be needed to realize the clinical utility of such AI-based tools.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37302656,
year = {2023},
author = {Sato, Y and Ueda-Arakawa, N and Takahashi, A and Miyara, Y and Hara, C and Kitajima, Y and Maruko, R and Kawai, M and Takahashi, H and Koizumi, H and Kawasaki, R and Maruyama-Inoue, M and Yanagi, Y and Iida, T and Takahashi, K and Sakamoto, T and Tsujikawa, A},
title = {Clinical Characteristics and Progression of Geographic Atrophy in a Japanese Population.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {10},
pages = {901-909},
doi = {10.1016/j.oret.2023.06.004},
pmid = {37302656},
issn = {2468-6530},
mesh = {Humans ; Male ; Aged ; Aged, 80 and over ; Female ; *Geographic Atrophy/diagnosis/complications ; Retrospective Studies ; East Asian People ; Fluorescein Angiography ; *Macular Degeneration/complications ; *Retinal Drusen/epidemiology ; },
abstract = {PURPOSE: To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population.<br><br>DESIGN: Retrospective, multicenter, observational study.<br><br>PARTICIPANTS: A total of 173 eyes from 173 patients from 6 university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged &#x2265; 50 years and had definite GA associated with AMD in at least 1 eye.<br><br>METHODS: The GA area was measured semiautomatically using fundus autofluorescence (FAF) images. In the follow-up group followed for > 6 months with FAF images, the GA progression rate was calculated by 2 methods: mm[2] per year and mm per year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate.<br><br>MAIN OUTCOME MEASURES: Clinical characteristics of GA and the GA progression rate.<br><br>RESULTS: The mean age was 76.8 &#xb1; 8.8 years, and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 &#xb1; 4.00 mm[2] (1.44 &#xb1; 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 (42.2%) eyes, respectively. The mean subfoveal choroidal thickness was 194.7 &#xb1; 105.5 &#x3bc;m. In the follow-up group (follow-up period: 46.2 &#xb1; 28.9 months), the mean GA progression rate was 1.01 &#xb1; 1.09 mm[2] per year (0.23 &#xb1; 0.18 mm/year [SQRT]). In the multivariable analysis, the baseline GA area (SQRT; P&#xa0;= 0.002) and the presence of reticular pseudodrusen (P < 0.001) were significantly associated with a greater GA progression rate (SQRT).<br><br>CONCLUSIONS: Certain clinical characteristics of GA in Asian populations may differ from those in White populations. Asian patients with GA showed male dominance and relatively thicker choroid than White patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in White populations. Large GA and reticular pseudodrusen were associated with a greater GA progression rate.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37302490,
year = {2023},
author = {Iftikhar, M and Dun, C and Schein, OD and Lum, F and Woreta, F},
title = {Cystoid Macular Edema after Cataract Surgery in the United States: IRIS® Registry (Intelligent Research in Sight) Analysis.},
journal = {Ophthalmology},
volume = {130},
number = {10},
pages = {1005-1014},
doi = {10.1016/j.ophtha.2023.06.001},
pmid = {37302490},
issn = {1549-4713},
mesh = {Humans ; Male ; United States/epidemiology ; Female ; *Macular Edema/diagnosis/epidemiology/etiology ; Retrospective Studies ; Case-Control Studies ; Postoperative Complications/epidemiology/etiology ; *Cataract Extraction/adverse effects ; *Phacoemulsification/adverse effects ; Registries ; *Cataract/complications ; },
abstract = {PURPOSE: To determine the incidence, risk factors, and visual outcomes of cystoid macular edema (CME) after cataract surgery in the United States.<br><br>DESIGN: Retrospective, longitudinal, case-control study.<br><br>PARTICIPANTS: Patients aged &#x2265; 18 years who underwent phacoemulsification cataract surgery.<br><br>METHODS: The American Academy of Ophthalmology IRIS&#xae; Registry (Intelligent Research in Sight) was used to analyze patients who underwent cataract surgery between 2016 and 2019. Patients who received a diagnosis of CME within 90 days after cataract surgery were classified as cases, and the rest were classified as controls. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with the development of CME as well as poor visual outcome (defined as a best-recorded visual acuity worse than 20/40 Snellen equivalent at postoperative month 12).<br><br>MAIN OUTCOME MEASURES: Incidence, demographics, baseline characteristics, and visual outcomes.<br><br>RESULTS: Of 3.1 million cataract surgeries performed during the study period, CME was diagnosed in 25 595 eyes (0.8%), with an average onset of 6 weeks. Patients with CME were more likely to be male, to be aged < 65 years, to be Black, and to have preexisting diabetic retinopathy. Patients with CME were more likely to have a poor visual outcome (OR, 1.75; 95% CI, 1.66-1.84; P < 0.001), with a mean best-recorded visual acuity of 20/30 at postoperative month 12 (compared with 20/25 for those without CME; P < 0.001). Other factors associated with a poor visual outcome included smoking, Medicaid insurance, non-White race, and baseline ocular comorbidities such as macular degeneration and retinal vein occlusion.<br><br>CONCLUSIONS: Although the incidence of CME after cataract surgery is low and most eyes achieve a visual acuity of 20/40 or better, there are significant outcome disparities that warrant further exploration.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37298038,
year = {2023},
author = {Markeviciute, A and Huang-Lung, J and Zemaitiene, R and Grzybowski, A},
title = {A Review of Ambient Air Pollution as a Risk Factor for Posterior Segment Ocular Diseases.},
journal = {Journal of clinical medicine},
volume = {12},
number = {11},
pages = {},
pmid = {37298038},
issn = {2077-0383},
abstract = {PURPOSE: To review the most recent evidence on the association of ambient air pollution with posterior segment ocular diseases.<br><br>METHODS: A search of the most recently published medical literature was performed in PubMed and Google Scholar on 10 December 2022. Articles published between 2018 and December 2022 were included in this rapid review. Studies that evaluated the association between ambient air pollutants (nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), particulate matters (PMs), total hydrocarbons (THC), nonmethane hydrocarbons (NMHC), benzene), and ocular posterior segment diseases (glaucoma, age-related macular degeneration (AMD), and retinal vascular diseases) were included.<br><br>RESULTS: Nineteen research articles met the inclusion criteria. Significant associations were found between PM2.5 and glaucoma, including primary open angle, primary angle closure, and normal tension glaucoma. An increased risk of AMD was linked to increased exposure to PM2.5, NO2, and CO. Single studies suggested that increased exposure to PM2.5 and PM10 is associated with diabetic retinopathy; THC and NMHC increased the risk of retinal vein occlusion; and CO, NO2, and PM10 are linked to an increased risk of central retinal artery occlusion.<br><br>CONCLUSIONS: There is increasing evidence that toxic air pollutants have an impact on posterior segment ocular diseases, hence determining it as a potential modifiable risk factor for visual impairment.},
}
@article {pmid37297855,
year = {2023},
author = {Chujo, S and Matsubara, H and Matsui, Y and Sugimoto, M and Kondo, M},
title = {Suspension of Anti-VEGF Treatment Does Not Affect Expansion of RPE Atrophy in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {11},
pages = {},
pmid = {37297855},
issn = {2077-0383},
abstract = {PURPOSE: To determine whether atrophy of the retinal pigment epithelium (RPE) in eyes with neovascular age-related macular degeneration (nAMD), which meets the criteria for the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatment, is associated with anti-VEGF treatments.<br><br>METHODS: Twelve eyes of 12 patients with nAMD who began anti-VEGF treatment and were followed for 1 year after meeting the criteria for the suspension of anti-VEGF were studied. Six eyes of six patients were placed in the continuation group, and six eyes of six patients were placed in the suspension group. The RPE atrophic area at the time of the last anti-VEGF treatment was set as the baseline size and that at 12 months after the baseline (Month 12) was taken as the final size. A comparison of the expansion rate of RPE atrophy between the two groups was made by the square-root transformed differences.<br><br>RESULTS: The expansion rate of atrophy was 0.55 (0.43, 0.72) mm/year in the continuation group and 0.33 (0.15, 0.41) mm/year in the suspension group. This difference was not significant. (p = 0.29).<br><br>CONCLUSIONS: Suspension of anti-VEGF treatments in eyes with nAMD does not alter the expansion rate of RPE atrophy.},
}
@article {pmid37297819,
year = {2023},
author = {Storp, JJ and Diener, R and Eter, N and Bormann, E and Treder, M},
title = {Submacular Hemorrhages Show No Significant Seasonal Variations in a European Cohort.},
journal = {Journal of clinical medicine},
volume = {12},
number = {11},
pages = {},
pmid = {37297819},
issn = {2077-0383},
abstract = {The aim of the article is to investigate the seasonality of acute submacular hemorrhages (SMHs) in a European population and analyze the influence of the seasons, arterial hypertension, and intake of anticoagulatory/antiplatelet (AC/AP) medication on hemorrhage size. This retrospective, monocentric study included 164 eyes of 164 patients treated for acute SMH at the University Hospital Münster, Germany, between 1 January 2016 and 31 December 2021. Data on the day of occurrence, hemorrhage size, and general patient characteristics were recorded. "Test for cyclic trends in incidence data" and the Chi-Square Test were applied to investigate seasonal variations in SMH incidence. Fisher's exact test was used to investigate the influence of the seasons, arterial hypertension, and intake of AC/AP medication on hemorrhage size. A statistical analysis did not reveal significant seasonal variations in the occurrence of SMHs (p = 0.81). While the seasons and the presence of systemic arterial hypertension did not exert a significant influence, the intake of AC/AP medication significantly affected the size of SMH (p = 0.03). In this European cohort, no significant seasonal variations of SMHs were observed. However, in patients with risk factors, such as neovascular age-related macular degeneration (nAMD), the chance of an increase in hemorrhage size should be considered when initiating AC/AP therapy.},
}
@article {pmid37296756,
year = {2023},
author = {Chłopowiec, AR and Karanowski, K and Skrzypczak, T and Grzesiuk, M and Chłopowiec, AB and Tabakov, M},
title = {Counteracting Data Bias and Class Imbalance-Towards a Useful and Reliable Retinal Disease Recognition System.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {11},
pages = {},
pmid = {37296756},
issn = {2075-4418},
abstract = {Multiple studies presented satisfactory performances for the treatment of various ocular diseases. To date, there has been no study that describes a multiclass model, medically accurate, and trained on large diverse dataset. No study has addressed a class imbalance problem in one giant dataset originating from multiple large diverse eye fundus image collections. To ensure a real-life clinical environment and mitigate the problem of biased medical image data, 22 publicly available datasets were merged. To secure medical validity only Diabetic Retinopathy (DR), Age-Related Macular Degeneration (AMD) and Glaucoma (GL) were included. The state-of-the-art models ConvNext, RegNet and ResNet were utilized. In the resulting dataset, there were 86,415 normal, 3787 GL, 632 AMD and 34,379 DR fundus images. ConvNextTiny achieved the best results in terms of recognizing most of the examined eye diseases with the most metrics. The overall accuracy was 80.46 ± 1.48. Specific accuracy values were: 80.01 ± 1.10 for normal eye fundus, 97.20 ± 0.66 for GL, 98.14 ± 0.31 for AMD, 80.66 ± 1.27 for DR. A suitable screening model for the most prevalent retinal diseases in ageing societies was designed. The model was developed on a diverse, combined large dataset which made the obtained results less biased and more generalizable.},
}
@article {pmid37295608,
year = {2023},
author = {Yoneda, K and Takeuchi, M and Yasukawa, T and Terasaki, H and Yamamoto, Y and Jujo, T and Wakuta, M and Matsubara, H and Mitamura, Y and Kato, A and Kondo, M and Kimura, K and Takagi, H and Gomi, F and Sakamoto, T and , },
title = {Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {10},
pages = {869-878},
doi = {10.1016/j.oret.2023.06.002},
pmid = {37295608},
issn = {2468-6530},
mesh = {Female ; Humans ; Angiogenesis Inhibitors ; Cohort Studies ; Japan/epidemiology ; *Macular Degeneration/drug therapy ; *Ranibizumab ; Male ; },
abstract = {PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting.<br><br>DESIGN: Retrospective multicenter cohort study.<br><br>PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year.<br><br>METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year.<br><br>MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity.<br><br>RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 &#xb1; 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP.<br><br>CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37294608,
year = {2023},
author = {Estarreja, J and Mendes, P and Silva, C and Camacho, P and Mateus, V},
title = {The Efficacy, Safety, and Efficiency of the Off-Label Use of Bevacizumab in Patients Diagnosed With Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis.},
journal = {JMIR research protocols},
volume = {12},
number = {},
pages = {e38658},
pmid = {37294608},
issn = {1929-0748},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is recognized as the leading cause of vision loss in older people. Considering the phenomenon of aging societies worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate, and late stages, with the early and intermediate stages being mainly asymptomatic, and the late stage being classified as geographic atrophy, neovascular AMD, or both. Current pharmacological treatments for neovascular AMD include anti-vascular endothelial growth factor agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported that the off-label use of intravitreally administered bevacizumab is effective. It is also lower cost than other agents, which makes it an interesting pharmacological approach.<br><br>OBJECTIVE: This review aims to evaluate the efficacy, safety, and efficiency of bevacizumab for the treatment of neovascular AMD.<br><br>METHODS: This review will only consider randomized controlled clinical trials that compare the use of bevacizumab with another pharmacological agent or a placebo in patients aged 50 years and older who are diagnosed with vascular AMD. It will exclude studies that include participants diagnosed with polypoidal choroidal vasculopathy or retinal angiomatous proliferation. To identify and select relevant articles, we will develop a highly sensitive search strategy and apply it in MEDLINE via the PubMed platform. Upon selection of the studies and analysis of the titles, abstracts, and full texts, the results will be presented according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis and extraction of the data will be performed by 2 independent reviewers. Risk of bias will be evaluated with the Critical Appraisal Skills Programme (CASP) checklist. Finally, the same reviewers will also perform a quality assessment of the included studies with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool.<br><br>RESULTS: The search strategy, after the application of the inclusion and exclusion criteria, identified 15 randomized clinical trials, which are currently being analyzed. This project has no funding and it has been developed by a multidisciplinary research team of pharmacologists and orthoptists. The study was initiated in May 2021 and it is expected to conclude by the end of 2023.<br><br>CONCLUSIONS: This review will provide a synthesis of current information and underlying evidence about the off-label use of bevacizumab in neovascular AMD. It will provide a clearer vision of a possible new pharmacological approach, as well as the most suitable treatment designs, for the treatment of neovascular AMD.<br><br>TRIAL REGISTRATION: PROSPERO CRD42021244931; https://tinyurl.com/p6m5ycpk.<br><br>DERR1-10.2196/38658.},
}
@article {pmid37294524,
year = {2023},
author = {Tadayoni, R and Jaffe, GJ and Holz, FG and Schmidt-Erfurth, U and Takahashi, K and Cheung, CMG and Hariprasad, SM and Gedif, K and Olsen, R and Best, C and Igwe, F and Kaiser, PK},
title = {Potential for Treatment Interval Extension in Eyes with nAMD Disease Activity Post Loading Phase in HAWK and HARRIER.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {4},
pages = {2209-2216},
pmid = {37294524},
issn = {2193-8245},
abstract = {INTRODUCTION: The HAWK and HARRIER studies evaluated the efficacy and safety of brolucizumab versus aflibercept in treatment-naïve eyes with neovascular age-related macular degeneration. Based on the study design, brolucizumab-treated eyes adjusted to a q8w regimen because the presence of disease activity (DA) at the end of the matched loading phase (Week 16) could not subsequently extend to a q12w interval. The aim of this post hoc analysis was to assess subsequent DA in this subgroup to determine the potential for interval extensions during the first year of treatment.<br><br>METHODS: Pooled data from the brolucizumab 6&#xa0;mg arms and aflibercept arms of HAWK and HARRIER were included. Presence of DA was determined by the masked investigator based on their assessment of functional and anatomical parameters measured by optical coherence tomography. DA was compared at DA assessments, conducted at Weeks 16, 20, 32, and 44; fluid was also assessed at the primary analysis at Week 48.<br><br>RESULTS: Fewer brolucizumab- (22.8%) than aflibercept-treated (32.2%) eyes had DA at the first DA assessment at Week 16. In eyes with investigator-identified DA at Week 16, BCVA change from baseline to Week 96 was comparable between treatment arms. Fewer brolucizumab- than aflibercept-treated eyes had DA at each subsequent DA assessment in Year 1: 31.8% vs 39.1% (Week 20), 27.3% vs 43.5% (Week 32), and 17.3% vs 31.2% (Week 44). Fewer eyes treated with brolucizumab than aflibercept had intraretinal and/or subretinal fluid: 35.3% vs 43.5% (Week 20), 55.8% vs 69.6% (Week 32), 30.0% vs 43.1% (Week 44), and 48.6% vs 68.6% (Week 48).<br><br>CONCLUSION: These findings indicate that, in eyes that still had DA 8&#xa0;weeks after the final dose of loading phase, brolucizumab-treated eyes had improved fluid resolution and higher potential for treatment interval extension than aflibercept-treated eyes during the first year of treatment.},
}
@article {pmid37294433,
year = {2023},
author = {Takahashi, K and Cheung, CMG and Iida, T and Lai, TYY and Ohji, M and Yanagi, Y and Kawano, M and Ohsawa, S and Suzuki, T and Kotecha, A and Lin, H and Patel, V and Swaminathan, B and Lee, WK and , },
title = {Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {11},
pages = {3125-3137},
pmid = {37294433},
issn = {1435-702X},
abstract = {PURPOSE: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Treatment-na&#xef;ve patients with nAMD were randomly assigned (1:1) to faricimab 6.0&#xa0;mg up to every 16&#xa0;weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0&#xa0;mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48.<br><br>RESULTS: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n&#x2009;=&#x2009;61; aflibercept n&#x2009;=&#x2009;59) and non-Asian country (faricimab n&#x2009;=&#x2009;604; aflibercept n&#x2009;=&#x2009;605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved&#x2009;&#x2265;&#x2009;Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile.<br><br>CONCLUSION: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03823287 (TENAYA); NCT03823300 (LUCERNE). Date of registration: January 30, 2019.},
}
@article {pmid37292179,
year = {2023},
author = {Wu, Z and Schmitz-Valckenberg, S and Blodi, BA and Holz, FG and Jaffe, GJ and Liakopoulos, S and Sadda, SR and Bonse, M and Brown, T and Choong, J and Clifton, B and Corradetti, G and Corvi, F and Dieu, AC and Dooling, V and Pak, JW and Saßmannshausen, M and Skalak, C and Thiele, S and Guymer, RH},
title = {Reticular Pseudodrusen: Interreader Agreement of Evaluation on OCT Imaging in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {3},
number = {4},
pages = {100325},
pmid = {37292179},
issn = {2666-9145},
abstract = {PURPOSE: To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence.<br><br>DESIGN: Interreader agreement study.<br><br>PARTICIPANTS: Twelve readers from 6 reading centers.<br><br>METHODS: All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to &#x2265; 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image.<br><br>MAIN OUTCOME MEASURES: Interreader agreement, as assessed by Gwet's first-order agreement coefficient (AC1).<br><br>RESULTS: When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or &#x2265; 5 Stage 2 or 3 lesions, and &#x2265; 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1&#xa0;= 0.60-0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or &#x2265; 5 Stage 2 or 3 lesions (AC1&#xa0;= 0.58-0.65) and increasing levels of agreement with increasing RPD stage (AC1&#xa0;= 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1&#xa0;= 0.68), but only fair agreement for this evaluation on selected B-scans (AC1&#xa0;= 0.30).<br><br>CONCLUSIONS: There was generally substantial or near-substantial-but not near-perfect-agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37291950,
year = {2023},
author = {Kågedal, M and Alskär, O and Petersson, K and Hanze, E and Maia, M and Lu, T and Vakhavkar, S and Quartino, A and Willis, JR and Jin, JY and Maass, KF},
title = {Population Pharmacokinetics of Ranibizumab Delivered via the Port Delivery System Implanted in the Eye in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical pharmacology},
volume = {63},
number = {11},
pages = {1210-1220},
doi = {10.1002/jcph.2290},
pmid = {37291950},
issn = {1552-4604},
mesh = {Humans ; *Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/pharmacokinetics/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacokinetics ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; },
abstract = {The port delivery system with ranibizumab (PDS) is designed to continuously deliver ranibizumab to maintain therapeutic drug concentrations in the vitreous of the eye for an extended duration. The PDS has been evaluated for the treatment of neovascular age-related macular degeneration in the Ladder (PDS 10, 40, and 100 mg/mL, with refill exchanges as needed, versus monthly intravitreal ranibizumab 0.5 mg), Archway (PDS 100 mg/mL with 24-week refill exchanges, versus monthly intravitreal ranibizumab 0.5 mg), and ongoing Portal (PDS 100 mg/mL with 24-week refill exchanges) clinical trials. Data from Ladder, Archway, and Portal were used to develop a population pharmacokinetics (PK) model to estimate the ranibizumab release rate from the PDS implant, describe ranibizumab PK in serum and aqueous humor, and predict the concentration in vitreous humor. A model was developed to adequately describe the serum and aqueous humor PK data, as suggested by goodness-of-fit plots as well as visual predictive checks. In the final model, the first-order implant release rate was estimated to be 0.00654 (1/day), corresponding to a half-life of 106 days, consistent with the implant release rate determined in vitro. The model-predicted vitreous concentrations achieved with PDS 100 mg/mL given every 24 weeks were below the intravitreal peak concentration and above the intravitreal trough concentration of ranibizumab over the entire 24-week refill interval. The results demonstrate a durable release of ranibizumab from the PDS with a half-life of 106 days, providing vitreous exposure to ranibizumab for at least 24 weeks that is within the range of exposure for monthly intravitreal treatment.},
}
@article {pmid37289448,
year = {2023},
author = {Woo, SJ and Bradvica, M and Vajas, A and Sagong, M and Ernest, J and Studnicka, J and Veith, M and Wylegala, E and Patel, S and Yun, C and Orski, M and Astakhov, S and Tóth-Molnár, E and Csutak, A and Enyedi, L and Kim, T and Oh, I and Jang, H and Sadda, SR},
title = {Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial.},
journal = {JAMA ophthalmology},
volume = {141},
number = {7},
pages = {668-676},
pmid = {37289448},
issn = {2168-6173},
mesh = {Humans ; Female ; Aged ; Male ; Angiogenesis Inhibitors/adverse effects ; *Biosimilar Pharmaceuticals/adverse effects ; Treatment Outcome ; Visual Acuity ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/adverse effects ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy/chemically induced ; Ranibizumab/therapeutic use ; },
abstract = {IMPORTANCE: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy.<br><br>OBJECTIVE: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD).<br><br>This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n&#x2009;=&#x2009;224) or AFL (n&#x2009;=&#x2009;225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up.<br><br>INTERVENTION: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity.<br><br>RESULTS: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 &#x3bc;m vs AFL, -115.7 &#x3bc;m). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable.<br><br>CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04450329.},
}
@article {pmid37288665,
year = {2023},
author = {Barone, F and Amaral, J and Bunea, I and Farnoodian, M and Gupta, R and Gupta, R and Baker, D and Phillips, MJ and Blanch, RJ and Maminishkis, A and Gamm, DM and Bharti, K},
title = {A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing.},
journal = {JCI insight},
volume = {8},
number = {11},
pages = {},
pmid = {37288665},
issn = {2379-3708},
mesh = {Choroid Diseases ; Child ; *Macular Degeneration/therapy ; Humans ; Retinal Pigment Epithelium ; Animals ; Retina/diagnostic imaging ; Swine ; *Retinal Degeneration/etiology/therapy ; },
abstract = {Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may slow down vision loss in late stages of age-related macular degeneration (AMD), a polygenic disease induced by RPE atrophy. However, accelerated development of effective cell therapies is hampered by the lack of large-animal models that allow testing safety and efficacy of clinical doses covering the human macula (20 mm2). We developed a versatile pig model to mimic different types and stages of retinal degeneration. Using an adjustable power micropulse laser, we generated varying degrees of RPE, PR, and CC damage and confirmed the damage by longitudinal analysis of clinically relevant outcomes, including analyses by adaptive optics and optical coherence tomography/angiography, along with automated image analysis. By imparting a tunable yet targeted damage to the porcine CC and visual streak - with a structure similar to the human macula - this model is optimal for testing cell and gene therapies for outer retinal diseases including AMD, retinitis pigmentosa, Stargardt, and choroideremia. The amenability of this model to clinically relevant imaging outcomes will facilitate faster translation to patients.},
}
@article {pmid37288355,
year = {2023},
author = {Huang, X and Zhang, L and Fu, Y and Zhang, M and Yang, Q and Peng, J},
title = {Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {11},
number = {},
pages = {1199922},
pmid = {37288355},
issn = {2296-4185},
abstract = {Age-related macular degeneration (AMD) is the predominant threat to human vision and ultimately results in blindness. With the increase in the aging population, it has become a more crucial issue to human health. AMD is a multifactorial disease with the unique feature of uncontrollable angiogenesis during initiation and progression. Although increasing evidence indicates that AMD is largely hereditary, the predominant efficient treatment is antiangiogenesis, which mainly involves VEGF and HIF-α as therapeutic targets. The repeated administration of this treatment over the long term, generally through intravitreal injection, has called for the introduction of long-term drug delivery systems, which are expected to be achieved by biomaterials. However, the clinical results of the port delivery system indicate that the optimization of medical devices toward prolonging the activities of therapeutic biologics in AMD therapy seems more promising. These results indicate that we should rethink the possibility and potential of biomaterials as drug delivery systems in achieving long-term, sustained inhibition of angiogenesis in AMD therapy. In this review, the etiology, categorization, risk factors, pathogenesis, and current clinical treatments of AMD are briefly introduced. Next, the development status of long-term drug delivery systems is discussed, and the drawbacks and shortages of these systems are emphasized. By comprehensively considering the pathological aspect and the recent application of drug delivery systems in AMD therapy, we hope to find a better solution for the further development of long-term therapeutic strategies for AMD.},
}
@article {pmid37288001,
year = {2023},
author = {Rai, BB and Rai, D and Maddess, T},
title = {Profile of Patients Treated with Intravitreal Anti-Vascular Endothelial Growth Factor Injections in Bhutan.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1565-1573},
pmid = {37288001},
issn = {1177-5467},
abstract = {PURPOSE: Ocular vascular diseases are common causes of visual impairment and blindness, for which anti-vascular endothelial growth factor (anti-VEGF) is the first-line therapy. Current study describes the profile of patients receiving intravitreal anti-VEGF injections (IVI), and gender variation in Bhutan. The study was designed to inform national health policy.<br><br>STUDY DESIGN: Retrospective cross-sectional study.<br><br>METHODS: We reviewed the surgical registers of the vitreoretinal (VR) units across Bhutan over three years. Patient demography, clinical findings, diagnostic tests performed, and diagnoses or indications for IVI were logged. A descriptive analysis was performed.<br><br>RESULTS: Despite limited availability of anti-VEGF, a total of 381 patients received IVI in operating theatres as mandated by the national guidelines. The majority of patients were males (230, 60.4%, p = 0.004). The mean age was 65.2 &#xb1; 13.5 years (range 13 years to 90 years), and a median of 69 years. The majority of the treated eyes (117, 30.7%) had BCVA <3/60 to light perception (PL), and another 51 eyes (13.4%) had < 6/60 to 3/60. The most common indication for IVI was neovascular age-related macular degeneration (nAMD) (168 cases, 42.2%), followed by retinal vein occlusion (RVO) (132 cases, 34.6%), diabetic macular oedema (DMO) and retinopathy (DR) (50 cases, 13.1%), and myopic choroidal neovascular membrane (11 cases, 0.03%).<br><br>CONCLUSION: Limited human resources for managing VR diseases in Bhutan are compounded by economic and geographic challenges. With increasing VR diseases such as nAMD and myopia and complications of systemic diseases such as DR, DMO and RVO, there is a need to improve VR services. Currently, anti-VEGF is procured only for a pooled patients requiring IVI, and patients are lost due to longer waiting periods. Bhutan needs to assess if females are reporting less or are not receiving treatment due to cultural barriers and social stigma.},
}
@article {pmid37286867,
year = {2023},
author = {Chandra, S and Tan, EY and Empeslidis, T and Sivaprasad, S},
title = {Tyrosine Kinase Inhibitors and their role in treating neovascular age-related macular degeneration and diabetic macular oedema.},
journal = {Eye (London, England)},
volume = {37},
number = {18},
pages = {3725-3733},
pmid = {37286867},
issn = {1476-5454},
mesh = {Humans ; *Macular Edema/drug therapy ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Tyrosine Kinase Inhibitors ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/drug therapy ; *Diabetic Retinopathy/complications/drug therapy ; Intravitreal Injections ; *Diabetes Mellitus ; },
abstract = {The advent of intravitreal anti-VEGF injections has revolutionised the treatment of both neovascular age-related macular degeneration (nAMD or wet AMD) and diabetic macular oedema (DMO). Despite their efficacy, anti-VEGF injections precipitate significant treatment burden for patients, caregivers and healthcare systems due to the high frequency of injections required to sustain treatment benefit. Therefore, there remains an unmet need for lower-burden therapies. Tyrosine kinase inhibitors (TKI) are a novel class of drugs that may have considerable potential in addressing this issue. This review will summarise and discuss the results of various pilot studies and clinical trials exploring the role of TKIs in treatment of nAMD and DMO, highlighting promising candidates and possible challenges in developments.},
}
@article {pmid37286795,
year = {2023},
author = {Colé, N and Thoele, J and Ullmer, C and Foxton, RH},
title = {Real-time measurements of vascular permeability in the mouse eye using vitreous fluorophotometry.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {9226},
pmid = {37286795},
issn = {2045-2322},
mesh = {Mice ; Animals ; Fluorophotometry ; *Diabetic Retinopathy/metabolism ; Capillary Permeability ; Vascular Endothelial Growth Factor A/metabolism ; *Macular Edema ; Vascular Endothelial Growth Factors/metabolism ; *Choroidal Neovascularization/pathology ; Disease Models, Animal ; },
abstract = {Breakdown of blood-retinal barrier integrity underpins pathological changes in numerous ocular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Whilst anti-vascular endothelial growth factor (VEGF) therapies have revolutionised disease treatment, novel therapies are still required to meet patients' unmet needs. To help develop new treatments, robust methods are needed to measure changes in vascular permeability in ocular tissues in animal models. We present here a method for detecting vascular permeability using fluorophotometry, which enables real-time measurements of fluorescent dye accumulation in different compartments of the mouse eye. We applied this method in several mouse models with different increased vascular leakage, including models of uveitis, diabetic retinopathy and choroidal neovascularization (CNV). Furthermore, in the JR5558 mouse model of CNV, we observed with anti-VEGF post-treatment a longitudinal reduction in permeability, in the same animal eyes. We conclude fluorophotometry is a useful method for measuring vascular permeability in the mouse eye, and can be used over multiple time points, without the need to sacrifice the animal. This method has the potential to be used in both basic research for studying the progression and factors underlying disease, but also for drug discovery and development of novel therapeutics.},
}
@article {pmid37285959,
year = {2023},
author = {Montolío-Marzo, S and Vidal-Oliver, L and Montolío-Marzo, E and Dolz-Marco, R and Gallego-Pinazo, R},
title = {Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: sterile vs. infectious.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {98},
number = {7},
pages = {367-376},
doi = {10.1016/j.oftale.2023.04.014},
pmid = {37285959},
issn = {2173-5794},
mesh = {Humans ; Diagnosis, Differential ; Retrospective Studies ; *Endophthalmitis/diagnosis ; *Macular Degeneration/complications ; Intravitreal Injections ; Inflammation/diagnosis/drug therapy/etiology ; },
abstract = {The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. Those drugs are associated to a higher rate of inflammatory adverse events compared to classic drugs. In this context it is essential to differentiate between sterile and infectious cases for a fast and effective treatment. The clinical similarities between infectious and sterile cases, the high rate of culture negative patients and the heterogeneity in the terminology used are obstacles for a correct diagnosis and report of these complications. Sterile cases appear early after the injection, before 48 h; or 20 days after in brolucizumab-related vasculitis cases. Infectious cases show up around the third day after injection and up to a week after it. A severe visual impairment, severe pain, severe hyperemia, hypopyon and a more severe intraocular inflammatory process are signs of a likely infectious origin. If the cause of the inflammation is uncertain we must follow up the patient closely or "tap and inject" antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation.},
}
@article {pmid37285697,
year = {2023},
author = {Abramovich, O and Pizem, H and Van Eijgen, J and Oren, I and Melamed, J and Stalmans, I and Blumenthal, EZ and Behar, JA},
title = {FundusQ-Net: A regression quality assessment deep learning algorithm for fundus images quality grading.},
journal = {Computer methods and programs in biomedicine},
volume = {239},
number = {},
pages = {107522},
doi = {10.1016/j.cmpb.2023.107522},
pmid = {37285697},
issn = {1872-7565},
mesh = {Humans ; *Deep Learning ; Algorithms ; Machine Learning ; Fundus Oculi ; *Macular Degeneration/diagnostic imaging ; },
abstract = {OBJECTIVE: Ophthalmological pathologies such as glaucoma, diabetic retinopathy and age-related macular degeneration are major causes of blindness and vision impairment. There is a need for novel decision support tools that can simplify and speed up the diagnosis of these pathologies. A key step in this process is to automatically estimate the quality of the fundus images to make sure these are interpretable by a human operator or a machine learning model. We present a novel fundus image quality scale and deep learning (DL) model that can estimate fundus image quality relative to this new scale.<br><br>METHODS: A total of 1245 images were graded for quality by two ophthalmologists within the range 1-10, with a resolution of 0.5. A DL regression model was trained for fundus image quality assessment. The architecture used was Inception-V3. The model was developed using a total of 89,947 images from 6 databases, of which 1245 were labeled by the specialists and the remaining 88,702 images were used for pre-training and semi-supervised learning. The final DL model was evaluated on an internal test set (n=209) as well as an external test set (n=194).<br><br>RESULTS: The final DL model, denoted FundusQ-Net, achieved a mean absolute error of 0.61 (0.54-0.68) on the internal test set. When evaluated as a binary classification model on the public DRIMDB database as an external test set the model obtained an accuracy of 99%.<br><br>SIGNIFICANCE: the proposed algorithm provides a new robust tool for automated quality grading of fundus images.},
}
@article {pmid37285214,
year = {2023},
author = {Nguyen, VP and Qian, W and Zhe, J and Henry, J and Wang, M and Liu, B and Zhang, W and Wang, X and Paulus, YM},
title = {Renally Clearable Ultraminiature Chain-Like Gold Nanoparticle Clusters for Multimodal Molecular Imaging of Choroidal Neovascularization.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {35},
number = {31},
pages = {e2302069},
pmid = {37285214},
issn = {1521-4095},
support = {P30EY007003/EY/NEI NIH HHS/United States ; K08 EY027458/EY/NEI NIH HHS/United States ; 1R41EY031219/EY/NEI NIH HHS/United States ; R01 EY033000/EY/NEI NIH HHS/United States ; 1K08EY027458/EY/NEI NIH HHS/United States ; P30 EY007003/EY/NEI NIH HHS/United States ; 1R01EY033000/EY/NEI NIH HHS/United States ; R41 EY031219/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Rabbits ; Gold ; Longitudinal Studies ; *Metal Nanoparticles ; *Choroidal Neovascularization/diagnostic imaging ; Tomography, Optical Coherence/methods ; Molecular Imaging/methods ; },
abstract = {Currently, available gold nanoparticles (GNPs) typically accumulate in the liver and spleen, leading to concerns for their long-term biosafety. To address this long-standing problem, ultraminiature chain-like gold nanoparticle clusters (GNCs) are developed. Via self-assembly of 7-8 nm GNP monomers, GNCs provide redshifted optical absorption and scattering contrast in the near-infrared window. After disassembly, GNCs turn back to GNPs with a size smaller than the renal glomerular filtration size cutoff, allowing their excretion via urine. A one-month longitudinal study in a rabbit eye model demonstrates that GNCs facilitate multimodal molecular imaging of choroidal neovascularization (CNV) in vivo, non-invasively, with excellent sensitivity and spatial resolution. GNCs targeting αv β3 integrins enhance photoacoustic and optical coherence tomography (OCT) signals from CNV by 25.3-fold and 150%, respectively. With excellent biosafety and biocompatibility demonstrated, GNCs render a first-of-its-kind nanoplatform for biomedical imaging.},
}
@article {pmid37284058,
year = {2023},
author = {Okonkwo, ON and Agweye, CT and Akanbi, T},
title = {Neuroprotection for Nonarteritic Central Retinal Artery Occlusion: Lessons from Acute Ischemic Stroke.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1531-1543},
pmid = {37284058},
issn = {1177-5467},
abstract = {Nonarteritic central retinal artery occlusion (NA-CRAO) is a variant of acute ischemic stroke (AIS) and is a cause of sudden severe loss of vision. There are guidelines by the American Heart Association and the American Stroke Association for the care of CRAO patients. This review explores the basis of retinal neuroprotection for CRAO and its potential for improving the outcome of NA-CRAO. Recently, there have been significant advances in research into the use of neuroprotection to treat retinal diseases, including retinal detachment, age-related macular degeneration, and inherited retinal diseases. Also, neuroprotective research in AIS has been extensive, and newer drugs tested, including Uric acid, Nerinetide, and Otaplimastat, with promising results. Progress in cerebral neuroprotection after AIS offers hope for retinal neuroprotection after CRAO; and a possibility of extrapolating research findings from AIS into CRAO. Combining neuroprotection and thrombolysis can extend the therapeutic window for NA-CRAO treatment and potentially improve outcomes. Experimented neuroprotection for CRAO includes Angiopoietin (Comp Ang1), KUS 121, Gene therapy (XIAP), and hypothermia. Efforts in the field of neuroprotection for NA-CRAO should focus on better imaging to delineate the penumbra after an acute episode of NA-CRAO (using a combination of high-definition optical coherence angiography and electrophysiology). Also, research should explore details of pathophysiologic mechanisms involved in NA-CRAO, allowing for further neuroprotective intervention, and closing the gap between preclinical and clinical neuroprotection.},
}
@article {pmid37280611,
year = {2023},
author = {Maruyama-Inoue, M and Yanagi, Y and Mohamed, S and Inoue, T and Kitajima, Y and Ikeda, S and Kadonosono, K},
title = {Hyperreflective material in patients with non-neovascular pachychoroid disease.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {255},
pmid = {37280611},
issn = {1471-2415},
mesh = {Humans ; *Choroid/blood supply ; *Retinal Pigment Epithelium ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; Neovascularization, Pathologic ; Retrospective Studies ; },
abstract = {BACKGROUND: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients.<br><br>METHODS: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes.<br><br>RESULTS: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period.<br><br>CONCLUSION: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.},
}
@article {pmid37280350,
year = {2023},
author = {Loewenstein, A and Berger, A and Daly, A and Creuzot-Garcher, C and Gale, R and Ricci, F and Zarranz-Ventura, J and Guymer, R},
title = {Save our Sight (SOS): a collective call-to-action for enhanced retinal care across health systems in high income countries.},
journal = {Eye (London, England)},
volume = {37},
number = {16},
pages = {3351-3359},
pmid = {37280350},
issn = {1476-5454},
mesh = {Humans ; Aged ; Developed Countries ; *Aging ; *Retinal Diseases ; },
abstract = {With a growing aging population, the prevalence of age-related eye disease and associated eye care is expected to increase. The anticipated growth in demand, coupled with recent medical advances that have transformed eye care for people living with retinal diseases, particularly neovascular age-related macular degeneration (nAMD) and diabetic eye disease, has presented an opportunity for health systems to proactively manage the expected burden of these diseases. To do so, we must take collective action to address existing and anticipated capacity limitations by designing and implementing sustainable strategies that enable health systems to provide an optimal standard of care. Sufficient capacity will enable us to streamline and personalize the patient experience, reduce treatment burden, enable more equitable access to care and ensure optimal health outcomes. Through a multi-modal approach that gathered unbiased perspectives from clinical experts and patient advocates from eight high-income countries, substantiated perspectives with evidence from the published literature and validated findings with the broader eye care community, we have exposed capacity challenges that are motivating the community to take action and advocate for change. Herein, we propose a collective call-to-action for the future management of retinal diseases and potential strategies to achieve better health outcomes for individuals at-risk of, or living with, retinal disease.},
}
@article {pmid37280266,
year = {2023},
author = {Sugasini, D and Park, JC and McAnany, JJ and Kim, TH and Ma, G and Yao, X and Antharavally, B and Oroskar, A and Oroskar, AA and Layden, BT and Subbaiah, PV},
title = {Improvement of retinal function in Alzheimer disease-associated retinopathy by dietary lysophosphatidylcholine-EPA/DHA.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {9179},
pmid = {37280266},
issn = {2045-2322},
support = {P30 EY001792/EY/NEI NIH HHS/United States ; R01 DK104927/DK/NIDDK NIH HHS/United States ; S10 OD010660/OD/NIH HHS/United States ; I01 BX004315/BX/BLRD VA/United States ; R01 EY030101/EY/NEI NIH HHS/United States ; R01 EY030842/EY/NEI NIH HHS/United States ; I01 BX003382/BX/BLRD VA/United States ; },
mesh = {Mice ; Animals ; Docosahexaenoic Acids/pharmacology ; Eicosapentaenoic Acid/pharmacology ; Lysophosphatidylcholines ; *Alzheimer Disease ; Amyloid beta-Peptides ; Retina ; *Retinal Diseases ; Diet ; },
abstract = {Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD, abnormalities in visual functions often precede them, and are increasingly being used as diagnostic and prognostic markers for the disease. Retina contains the highest concentration of the essential fatty acid docosahexaenoic acid (DHA) in the body, and its deficiency is associated with several retinal diseases including diabetic retinopathy and age related macular degeneration. In this study, we tested the hypothesis that enriching retinal DHA through a novel dietary approach could ameliorate symptoms of retinopathy in 5XFAD mice, a widely employed model of AD. The results show that 5XFAD mice have significantly lower retinal DHA compared to their wild type littermates, and feeding the lysophosphatidylcholine (LPC) form of DHA and eicosapentaenoic acid (EPA) rapidly normalizes the DHA levels, and increases retinal EPA by several-fold. On the other hand, feeding similar amounts of DHA and EPA in the form of triacylglycerol had only modest effects on retinal DHA and EPA. Electroretinography measurements after 2 months of feeding the experimental diets showed a significant improvement in a-wave and b-wave functions by the LPC-diet, whereas the TAG-diet had only a modest benefit. Retinal amyloid β levels were decreased by about 50% by the LPC-DHA/EPA diet, and by about 17% with the TAG-DHA/EPA diet. These results show that enriching retinal DHA and EPA through dietary LPC could potentially improve visual abnormalities associated with AD.},
}
@article {pmid37278678,
year = {2023},
author = {Lad, EM and Chakravarthy, U},
title = {The Issue of End Point Discordance in Dry Age-Related Macular Degeneration: How Might Clinical Trials Demonstrate a Functional Benefit?.},
journal = {Ophthalmology},
volume = {130},
number = {9},
pages = {890-892},
doi = {10.1016/j.ophtha.2023.05.020},
pmid = {37278678},
issn = {1549-4713},
mesh = {Humans ; *Geographic Atrophy ; *Macular Degeneration/drug therapy ; *Eye Diseases ; },
}
@article {pmid37278426,
year = {2023},
author = {Nakayama, LF and Mitchell, WG and Shapiro, S and Santiago, APD and Phanphruk, W and Kalua, K and Celi, LA and Regatieri, CVS},
title = {Sociodemographic disparities in ophthalmological clinical trials.},
journal = {BMJ open ophthalmology},
volume = {8},
number = {1},
pages = {},
pmid = {37278426},
issn = {2397-3269},
mesh = {United States/epidemiology ; Humans ; *Ophthalmology ; Ethnicity ; Minority Groups ; *Cataract ; *Glaucoma/diagnosis ; },
abstract = {INTRODUCTION: In ophthalmology, clinical trials (CTs) guide the treatment of diseases such as diabetic retinopathy, myopia, age-related macular degeneration, glaucoma and keratoconus with distinct presentations, pathological characteristics and responses to treatment in minority populations.Reporting gender and race and ethnicity in healthcare studies is currently recommended by National Institutes of Health (NIH) and Food and Drug Administration (FDA) guidelines to ensure representativeness and generalisability; however, CT results that include this information have been limited in the past 30 years.The objective of this review is to analyse the sociodemographic disparities in ophthalmological phases III and IV CT based on publicly available data.<br><br>METHODS: This study included phases III and IV complete ophthalmological CT available from clinicaltrials.org, and describes the country distribution, race and ethnicity description and gender, and funding characteristics.<br><br>RESULTS: After a screening process, we included 654 CTs, with findings that corroborate the previous CT reviews' findings that most ophthalmological participants are white and from high-income countries. A description of race and ethnicity is reported in 37.1% of studies but less frequently included within the most studied ophthalmological specialty area (cornea, retina, glaucoma and cataracts). The incidence of race and ethnicity reporting has improved during the past 7&#x2009;years.<br><br>DISCUSSION: Although NIH and FDA promote guidelines to improve generalisability in healthcare studies, the inclusion of race and ethnicity in publications and diverse participants in ophthalmological CT is still limited. Actions from the research community and related stakeholders are necessary to increase representativeness and guarantee generalisability in ophthalmological research results to optimise care and reduce related healthcare disparities.},
}
@article {pmid37278418,
year = {2023},
author = {Bonnet, LA and Singh, V and Ah-Chan, J},
title = {Palmerston North Interventional Rapid Avastin Treat and Extend (PIRATE) study protocol; meeting the medical retina service needs of our ageing population.},
journal = {BMJ open ophthalmology},
volume = {8},
number = {1},
pages = {},
pmid = {37278418},
issn = {2397-3269},
mesh = {Humans ; Middle Aged ; Bevacizumab/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; Ranibizumab ; Prospective Studies ; *Macular Degeneration/drug therapy ; Treatment Outcome ; Visual Acuity ; Intravitreal Injections ; Retina ; Aging ; Randomized Controlled Trials as Topic ; },
abstract = {INTRODUCTION: As the rates of age-related macular denegation exponentially increase, new innovation is required to address the challenges faced by our ageing population. The aim of the Palmerston North Interventional Rapid Avastin Treat and Extend (PIRATE) study is to establish the safety and efficacy of rapid treatment extension of bevacizumab (Avastin) in patients with low-risk neovascular age-related macular degeneration (nAMD).<br><br>METHODS AND ANALYSIS: The PIRATE study is a monocentric, non-blinded, open-label randomised control trial. Participants over the age of 50 years with low-risk nAMD characteristics will be recruited in a prospective manner and randomised into treatment and control groups. Rapid treatment extension by 4&#x2009;weeks will be applied in the treatment group, with the standard 2-week treatment extension occurring among controls. Participants will enter the trial after initial treatment induction consisting of three bevacizumab injections, 1&#x2009;month apart. The primary outcome of best-corrected visual acuity will be assessed along with predetermined secondary outcomes at a study duration of 12 months (initial) and 24&#x2009;months (total).<br><br>TRIAL REGISTRATION NUMBER: ACTRN12622001246774p.},
}
@article {pmid37278414,
year = {2023},
author = {Fang, WY and Rama Raj, P and Wu, Z and Abbott, C and Luu, CD and Naughton, M and Guymer, RH},
title = {Role of sleep-disordered breathing in age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {8},
number = {1},
pages = {},
pmid = {37278414},
issn = {2397-3269},
mesh = {Humans ; Case-Control Studies ; *Sleep Apnea, Obstructive/complications ; *Macular Degeneration/complications ; *Retinal Drusen/complications ; Retina ; },
abstract = {AIMS: To examine the association between obstructive sleep apnoea (OSA) and age-related macular degeneration (AMD), and the subphenotype of AMD with reticular pseudodrusen (RPD).<br><br>METHODS: Case-control study with 351 participants (211 AMD and 140 controls) using the Epworth Sleepiness Scale (ESS) and the STOP-BANG Questionnaire (SBQ) validated sleep questionnaires. Participant risk of having moderate-to-severe OSA was determined using a binary risk scale based on the ESS and SBQ combined and an ordinal risk scale based on the SBQ. A prior diagnosis of OSA and whether receiving assisted breathing treatment was also ascertained. Retinal imaging allowed AMD and RPD determination.<br><br>RESULTS: Higher risk of moderate-to-severe OSA according to the binary and ordinal scales was not associated with the presence of AMD (p&#x2265;0.519) nor AMD with RPD (p&#x2265;0.551). Per point increase in ESS or SBQ questionnaire score was also not associated with AMD nor AMD with RPD (p&#x2265;0.252). However, being on assisted breathing treatment for diagnosed OSA was significantly associated with a higher likelihood of having AMD with RPD, but not all AMD, (OR 3.70; p=0.042&#x2009;and OR 2.70; p=0.149, respectively), when compared with those without diagnosed OSA on treatment.<br><br>CONCLUSIONS: Formally diagnosed OSA undergoing treatment, increased the likelihood of having AMD with RPD, but not overall AMD compared with those who were not undergoing treatment. Risk-based OSA questionnaires showed no difference in risk for all AMD or AMD with RPD. Future research, using formal sleep studies could further explore the potential role of nocturnal hypoxia in AMD.},
}
@article {pmid37274013,
year = {2023},
author = {Rahimy, E and Khan, MA and Ho, AC and Hatfield, M and Nguyen, TH and Jones, D and McKeown, A and Borkar, D and Leng, T and Ribeiro, R and Holekamp, N},
title = {Progression of Geographic Atrophy: Retrospective Analysis of Patients from the IRIS® Registry (Intelligent Research in Sight).},
journal = {Ophthalmology science},
volume = {3},
number = {4},
pages = {100318},
pmid = {37274013},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate disease progression and associated vision changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in 1 eye and GA or neovascular AMD (nAMD) in the fellow eye using a large dataset from routine clinical practice.<br><br>DESIGN: Retrospective analysis of clinical data over 24 months.<br><br>SUBJECTS: A total of 256 635 patients with GA from the American Academy of Ophthalmology (Academy) IRIS&#xae; Registry (Intelligent Research in Sight) Registry (January 2016 to December 2017).<br><br>METHODS: Patients with &#x2265; 24 months of follow-up were grouped by fellow-eye status: Cohort 1, GA:GA; Cohort 2, GA:nAMD, each with (subfoveal) and without subfoveal (nonsubfoveal) involvement. Eyes with history of retinal disease other than AMD were excluded. Sensitivity analysis included patients who were managed by retina specialists and had a record of imaging within 30 days of diagnosis.<br><br>MAIN OUTCOME MEASURES: Change in visual acuity (VA), occurrence of new-onset nAMD, and GA progression from nonsubfoveal to subfoveal.<br><br>RESULTS: In total, 69 441 patients were included: 44 120 (64%) GA:GA and 25 321 (36%) GA:nAMD. Otherwise eligible patients (57 788) were excluded due to follow-up < 24 months. In both GA:GA and GA:nAMD cohorts, nonsubfoveal study eyes had better mean (standard deviation) VA at index (67 [19.3] and 66 [20.3] letters) than subfoveal eyes (59 [23.9] and 47 [26.9] letters), and 24-month mean VA changes were similar for nonsubfoveal (-7.6 and&#xa0;-6.2) and subfoveal (-7.9 and&#xa0;-6.5) subgroups. Progression to subfoveal GA occurred in 16.7% of nonsubfoveal study eyes in the GA:GA cohort and 12.5% in the GA:nAMD cohort. More new-onset study-eye nAMD was observed in the GA:nAMD (21.6%) versus GA:GA (8.2%) cohorts. Sensitivity analysis supported the robustness of the observations in the study.<br><br>CONCLUSIONS: This retrospective analysis describes the natural progression of GA lesions and the decline in VA associated with the disease.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37273909,
year = {2023},
author = {Wang, W and Lin, P and Wang, S and Zhang, G and Chen, C and Lu, X and Zhuang, Y and Su, J and Wang, H and Xu, L},
title = {In-depth mining of single-cell transcriptome reveals the key immune-regulated loops in age-related macular degeneration.},
journal = {Frontiers in molecular neuroscience},
volume = {16},
number = {},
pages = {1173123},
pmid = {37273909},
issn = {1662-5099},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD), an ever-increasing ocular disease, has become one of the leading causes of irreversible blindness. Recent advances in single-cell genomics are improving our understanding of the molecular mechanisms of AMD. However, the pathophysiology of this multifactorial disease is complicated and still an ongoing challenge. To better understand disease pathogenesis and identify effective targets, we conducted an in-depth analysis of the single-cell transcriptome of AMD.<br><br>METHODS: The cell expression specificity of the gene (CESG) was selected as an index to identify the novel cell markers. A computational framework was designed to explore the cell-specific TF regulatory loops, containing the interaction of gene pattern signatures, transcription factors regulons, and differentially expressed genes.<br><br>RESULTS: Three potential novel cell markers were DNASE1L3 for endothelial cells, ABCB5 for melanocytes, and SLC39A12 for RPE cells detected. We observed a notable change in the cell abundance and crosstalk of fibroblasts cells, melanocytes, schwann cells, and T/NK cells between AMD and controls, representing a complex cellular ecosystem in disease status. Finally, we identified six cell type related and three disease-associated ternary loops and elaborated on the robust association between key immune-pathway and AMD.<br><br>DISCUSSION: In conclusion, this study facilitates the optimization of screening for AMD-related receptor ligand pathways and proposes to further improve the interpretability of disease associations from single-cell data. It illuminated that immune-related regulation paths could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, providing insights into AMD diagnosis and potential interventions.},
}
@article {pmid37271137,
year = {2023},
author = {Kalaw, FGP and Alex, V and Walker, E and Bartsch, DU and Freeman, WR and Borooah, S},
title = {Inner Retinal Thickness and Vasculature in Patients with Reticular Pseudodrusen.},
journal = {Ophthalmic research},
volume = {66},
number = {1},
pages = {885-891},
doi = {10.1159/000530799},
pmid = {37271137},
issn = {1423-0259},
mesh = {Humans ; Choroid ; *Retinal Drusen/diagnosis ; Retina ; *Macular Degeneration/diagnosis ; *Geographic Atrophy ; Tomography, Optical Coherence/methods ; },
abstract = {INTRODUCTION: The aim of this study was to investigate retinal layer thickness and vessel density differences between patients with reticular pseudodrusen (RPD) and intermediate dry age-related macular degeneration (iAMD).<br><br>METHODS: Participants included in the study were patients diagnosed by retinal specialists with RPD, iAMD, and both RPD and iAMD at our academic referral center, seen from May 2021 until February 2022. The central 3 mm retinal thickness was measured using spectral-domain optical coherence tomography (Heidelberg Spectralis HRA+OCT System; Heidelberg Engineering, Heidelberg, Germany). Individual retinal thickness measurements were obtained from the innermost layer (nerve fiber layer) until the outermost layer (retinal pigment epithelium [RPE]). Each thickness measurement was subdivided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. For the vessel density, OCT angiography from the Heidelberg Spectralis System was measured using proprietary third-party software (AngioTool; National Institutes of Health, National Cancer Institute, Bethesda, MD). Clinical and demographic characteristics were compared across the three groups (iAMD, RPD, iAMD and RPD) and analyzed with necessary adjustments. Linear mixed-effects models with necessary corrections were employed to compare continuous eye-level measurements between our three groups as well as in pairwise fashion using the R statistical programming software (R version 4.2.1).<br><br>RESULTS: A total of 25 eyes of 17 patients with RPD, 20 eyes of 15 patients with iAMD, and 14 eyes of 9 patients with both iAMD and RPD were analyzed. Retinal thickness analysis identified that the superior inner (p = 0.028) and superior outer (p = 0.027) maculas of eyes with both iAMD and RPD were significantly thinner than those with iAMD alone. In eyes with RPD, the superior inner and superior outer RPE (p = 0.011 and p = 0.05, respectively), outer plexiform layer (p = 0.003 and p = 0.013, respectively), and inner nuclear layer (p = 0.034 and p = 0, respectively) were noted to be thinner compared to eyes with iAMD alone. In addition, the macular deep capillary plexus vessel density was significantly reduced in eyes with RPD compared to eyes with iAMD (p = 0.017).<br><br>CONCLUSION: Patients with RPD had inner retinal structural as well as vascular changes compared to iAMD patients. Inner retinal vascular attenuation should be investigated further to see if there is a causal association with retinal thinning.},
}
@article {pmid37270615,
year = {2023},
author = {Stretton, B and Kovoor, JG and Bacchi, S and Chan, WO},
title = {A common factor? Sleep, macular degeneration and neurodegenerative disease.},
journal = {Eye (London, England)},
volume = {37},
number = {18},
pages = {3877},
pmid = {37270615},
issn = {1476-5454},
mesh = {Humans ; *Neurodegenerative Diseases ; *Macular Degeneration ; Sleep ; },
}
@article {pmid37269465,
year = {2023},
author = {Ghanbarnia, MJ and Hosseini, SR and Ghasemi, M and Roustaei, GA and Mekaniki, E and Ghadimi, R and Bijani, A and Rasoulinejad, SA},
title = {Association of age-related eye diseases with cognitive frailty in older adults: a population-based study.},
journal = {Aging clinical and experimental research},
volume = {35},
number = {8},
pages = {1731-1740},
pmid = {37269465},
issn = {1720-8319},
mesh = {Humans ; Female ; Middle Aged ; Aged ; Male ; *Frailty/epidemiology/psychology ; Cross-Sectional Studies ; Iran ; *Cataract/complications/epidemiology ; *Glaucoma ; *Cognitive Dysfunction/epidemiology ; Cognition ; Frail Elderly/psychology ; },
abstract = {BACKGROUND: Age-related eye diseases and cognitive frailty (CF) are both important predictors of adverse health outcomes in older adults, however, little is known about their association.<br><br>AIMS: To demonstrate the association between age-related eye diseases and cognitive frailty in a population of Iranian older adults.<br><br>METHODS: In this cross-sectional, population-based study, we included 1136 individuals (female n&#x2009;=&#x2009;514) aged 60&#xa0;years and older (mean 68.8&#x2009;&#xb1;&#x2009;6.7&#xa0;years) who participated in the second cycle of the Amirkola Health and Aging Project (AHAP) between 2016 and 2017. Cognitive function and frailty were evaluated based on Mini-Mental State Examination (MMSE) and the FRAIL scale respectively. Cognitive frailty was defined as coexistence of cognitive impairment (CI) and physical frailty (PF), excluding confirmed cases of dementia such as Alzheimer's disease. Cataract, diabetic retinopathy (DR), age-related macular degeneration (AMD), elevated intraocular pressure (IOP&#x2009;&#x2265;&#x2009;21&#xa0;mmHg) and glaucoma suspects (vertical cup to disc ratio (VCDR)&#x2009;&#x2265;&#x2009;0.6) were diagnosed based on standardized grading protocols. Associations between eye diseases and cognitive frailty were evaluated through binary logistic regression analysis.<br><br>RESULTS: Overall, CI, PF and CF were observed in 257 (22.6%), 319 (28.1%) and 114 (10.0%) participants respectively. After adjusting for confounders and ophthalmic conditions, individuals with cataract were more likely to have CF (OR 1.66; p-value 0.043), while DR, AMD, elevated IOP and glaucoma suspects (OR 1.32, 1.62, 1.42, 1.36, respectively) were not significantly associated with CF. Furthermore, cataract was significantly associated with CI (OR 1.50; p-value 0.022), but not with frailty (OR 1.18; p-value 0.313).<br><br>CONCLUSION: Older adults with cataract were more likely to have cognitive frailty and cognitive impairment. This association demonstrates the implications of age-related eye diseases beyond ophthalmology and substantiates the need for further research involving cognitive frailty in the context of eye diseases and visual impairment.},
}
@article {pmid37268418,
year = {2023},
author = {Madugula, SS and Vilkhu, R and Shah, NP and Grosberg, LE and Kling, A and Gogliettino, AR and Nguyen, H and Hottowy, P and Sher, A and Litke, AM and Chichilnisky, EJ},
title = {Inference of Electrical Stimulation Sensitivity from Recorded Activity of Primate Retinal Ganglion Cells.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {43},
number = {26},
pages = {4808-4820},
pmid = {37268418},
issn = {1529-2401},
support = {R01 EY021271/EY/NEI NIH HHS/United States ; T32 MH020016/MH/NIMH NIH HHS/United States ; F30 EY030776/EY/NEI NIH HHS/United States ; P30 EY019005/EY/NEI NIH HHS/United States ; R01 EY029247/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Male ; Female ; Humans ; *Retinal Ganglion Cells/physiology ; Action Potentials/physiology ; *Retina/physiology ; Primates ; Electric Stimulation/methods ; },
abstract = {High-fidelity electronic implants can in principle restore the function of neural circuits by precisely activating neurons via extracellular stimulation. However, direct characterization of the individual electrical sensitivity of a large population of target neurons, to precisely control their activity, can be difficult or impossible. A potential solution is to leverage biophysical principles to infer sensitivity to electrical stimulation from features of spontaneous electrical activity, which can be recorded relatively easily. Here, this approach is developed and its potential value for vision restoration is tested quantitatively using large-scale multielectrode stimulation and recording from retinal ganglion cells (RGCs) of male and female macaque monkeys ex vivo Electrodes recording larger spikes from a given cell exhibited lower stimulation thresholds across cell types, retinas, and eccentricities, with systematic and distinct trends for somas and axons. Thresholds for somatic stimulation increased with distance from the axon initial segment. The dependence of spike probability on injected current was inversely related to threshold, and was substantially steeper for axonal than somatic compartments, which could be identified by their recorded electrical signatures. Dendritic stimulation was largely ineffective for eliciting spikes. These trends were quantitatively reproduced with biophysical simulations. Results from human RGCs were broadly similar. The inference of stimulation sensitivity from recorded electrical features was tested in a data-driven simulation of visual reconstruction, revealing that the approach could significantly improve the function of future high-fidelity retinal implants.SIGNIFICANCE STATEMENT This study demonstrates that individual in situ primate retinal ganglion cells of different types respond to artificially generated, external electrical fields in a systematic manner, in accordance with theoretical predictions, that allows for prediction of electrical stimulus sensitivity from recorded spontaneous activity. It also provides evidence that such an approach could be immensely helpful in the calibration of clinical retinal implants.},
}
@article {pmid37266932,
year = {2023},
author = {Zhang, Y and Huang, J and Liang, Y and Huang, J and Fu, Y and Chen, N and Lu, B and Zhao, C},
title = {Clearance of lipid droplets by chimeric autophagy-tethering compound ameliorates the age-related macular degeneration phenotype in mice lacking APOE.},
journal = {Autophagy},
volume = {19},
number = {10},
pages = {2668-2681},
pmid = {37266932},
issn = {1554-8635},
mesh = {Mice ; Animals ; *Lipid Droplets/metabolism ; Autophagy ; *Macular Degeneration/drug therapy/metabolism/pathology ; Retinal Pigment Epithelium/metabolism ; Apolipoproteins E ; Phenotype ; Apolipoproteins/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, and there is currently no clinical treatment targeting the primary impairment of AMD. The earliest clinical hallmark of AMD is drusen, which are yellowish spots mainly composed of lipid droplets (LDs) accumulated under the retinal pigment epithelium (RPE). However, the potential pathogenic role of this excessive LD accumulation in AMD is yet to be determined, partially due to a lack of chemical tools to manipulate LDs specifically. Here, we employed our recently developed Lipid Droplets·AuTophagy Tethering Compounds (LD∙ATTECs) to degrade LDs and to evaluate its consequence on the AMD-like phenotypes in apoe[-/-] (apolipoprotein E; B6/JGpt-Apoe[em1Cd82]/Gpt) mouse model. apoe[-/-] mice fed with high-fat diet (apoe[-/-]-HFD) exhibited excessive LD accumulation in the retina, particularly with AMD-like phenotypes including RPE degeneration, Bruch's membrane (BrM) thickening, drusen-like deposits, and photoreceptor dysfunction. LD·ATTEC treatment significantly cleared LDs in RPE/choroidal tissues without perturbing lipid synthesis-related proteins and rescued RPE degeneration and photoreceptor dysfunction in apoe[-/-]-HFD mice. This observation implied a causal relationship between LD accumulation and AMD-relevant phenotypes. Mechanically, the apoe[-/-]-HFD mice exhibited elevated oxidative stress and inflammatory signals, both of which were mitigated by the LD·ATTEC treatment. Collectively, this study demonstrated that LD accumulation was a trigger for the process of AMD and provided entry points for the treatment of the initial insult of AMD by degrading LDs.Abbreviations: AMD: age-related macular degeneration; APOE: apolipoprotein E; ATTECs: autophagy-tethering compounds; BODIPY: boron-dipyrromethene; BrM: Bruch's membrane; ERG: electroretinogram; HFD: high-fat diet; LD·ATTECs: Lipid Droplets·AuTophagy Tethering Compounds; LDs: lipid droplets; OA: oleic acid; OPL: outer plexiform layer; ROS: reactive oxygen species; RPE: retinal pigment epithelium.},
}
@article {pmid37266673,
year = {2023},
author = {Fieß, A and Mildenberger, E and Pfeiffer, N and Schuster, AK},
title = {[Ophthalmological long-term sequelae of premature birth-Persisting into adulthood : Eye development and premature birth anamnesis].},
journal = {Die Ophthalmologie},
volume = {120},
number = {6},
pages = {597-607},
pmid = {37266673},
issn = {2731-7218},
mesh = {Infant, Newborn ; Adult ; Female ; Adolescent ; Humans ; *Premature Birth ; Quality of Life ; Tomography, Optical Coherence ; Retina ; *Retinopathy of Prematurity ; },
abstract = {BACKGROUND: Premature birth and the postnatal occurrence of retinopathy of prematurity (ROP) are the main risk factors for reduced visual acuity and blindness in childhood and adolescence accompanied by numerous morphological ocular changes.<br><br>OBJECTIVE: It can be assumed that these alterations persist throughout life and could represent a&#xa0;potential risk factor for ocular diseases, although little is known to date about the long-term effects of prematurity on ocular function and morphology in adulthood.<br><br>METHODS: The aim of the present study is to review the literature on the long-term effects of prematurity and associated factors.<br><br>RESULTS: Individuals born preterm exhibit reduced visual acuity, lower visual quality of life, and steeper corneal configuration in adulthood. Furthermore, individuals with advanced ROP and need for ROP treatment are at particularly high risk for myopic refractive error, the occurrence of strabismus, and increased lens opacities with thicker lenses. Low gestational age is associated with thinner peripapillary retinal nerve fiber layer thickness as well as thicker foveal retinal thickness and more frequent occurrence of foveal hypoplasia. In addition, data from the Gutenberg Health Study showed that low birth weight as a&#xa0;surrogate marker for prematurity and fetal growth restriction are associated with an increased prevalence of age-related macular degeneration as well as more frequently with diabetes and consequently diabetic retinopathy.<br><br>DISCUSSION: Premature birth and associated factors lead to life-long functional and morphological ocular changes. There is evidence that this can lead to retinal diseases later in life and thus, there appear to be fetal origins for adult eye disease. This may have implications for ophthalmic controls and its intervals in adulthood.},
}
@article {pmid37265519,
year = {2023},
author = {Jiang, B and Jiang, C and Li, J and Lu, P},
title = {Trends and disparities in disease burden of age-related macular degeneration from 1990 to 2019: Results from the global burden of disease study 2019.},
journal = {Frontiers in public health},
volume = {11},
number = {},
pages = {1138428},
pmid = {37265519},
issn = {2296-2565},
mesh = {Adult ; Male ; Female ; Humans ; Middle Aged ; *Global Burden of Disease ; Retrospective Studies ; Cost of Illness ; Prevalence ; *Macular Degeneration/epidemiology ; },
abstract = {OBJECTIVES: This study aims to estimate the trends and disparities in the worldwide burden for health of AMD, overall and by age, sex, socio-demographic index (SDI), region, and nation using prevalence and years lived with disability (YLDs) from Global Burden of Disease (GBD) study 2019.<br><br>METHODS: This retrospective study presents the prevalent AMD cases and YLDs from 1990-2019, as well as the age-standardized prevalence rate (ASPR) and age-standardized YLD rate (ASYR) of AMD. To measure changes over time, estimated annual percentage changes (EAPCs) of the age-standardized rates (ASRs) were analyzed globally, then studied further by sex, SDI, region, and nation. We included data from the 2019 Global Burden of Disease (GBD) database to examine AMD prevalence and YLDs from 1990-2019 in 204 countries and territories, as well as demographic information such as age, sex, SDI, region, and nation.<br><br>RESULTS: Globally, the number of prevalent AMD cases increased from 3,581,329.17 (95% uncertainty interval [UI], 3,025,619.4-4,188,835.7) in 1990 to 7,792,530 (95% UI, 6,526,081.5-9,159,394.9) in 2019, and the number of YLDs increased from 296,771.93 (95% uncertainty interval [UI], 205,462.8-418,699.82) in 1990 to 564,055.1 (95% UI, 392,930.7-789,194.64) in 2019. The ASPR of AMD had a decreased trend with an EAPC of -0.15 (95% confidence interval [CI], -0.2 to -0.11) from 1990 to 2019, and the ASYR of AMD showed a decreased trend with an EAPC of -0.71 (95% confidence interval [CI], -0.78 to -0.65) during this period. The prevalence and YLDs of AMD in adults over 50&#x2009;years of age showed a significant increase. The prevalence and YLDs of AMD were significantly higher in females than males, overall. The ASPRs and ASYRs in low SDI regions was greater than in high SDI regions from 1990 to 2019. In addition, increases in prevalence and YLDs differed by regions and nations, as well as level of socio-economic development.<br><br>CONCLUSION: The number of prevalent cases and YLDs due to AMD increased over 30 years and were directly linked to age, sex, socio-economic status, and geographic location. These findings can not only guide public health work but also provide an epidemiological basis for global strategy formulation regarding this global health challenge.},
}
@article {pmid37263796,
year = {2023},
author = {Chen, YX and Zhang, YQ and Chen, CZ and Dai, H and Li, SY and Ma, X and Sun, XD and Tang, SB and Wang, YS and Wei, WB and Wen, F and Xu, GZ and Yu, WH and Zhang, MX and Zhao, MW and Zhang, Y and Qi, F and Xu, X and Li, XX},
title = {Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).},
journal = {Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih},
volume = {38},
number = {2},
pages = {77-93},
doi = {10.24920/004213},
pmid = {37263796},
issn = {1001-9294},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Polypoidal Choroidal Vasculopathy ; Combined Modality Therapy ; Vascular Endothelial Growth Factor A ; Retinal Hemorrhage/drug therapy ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Retrospective Studies ; },
abstract = {Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&amp;E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.},
}
@article {pmid37263398,
year = {2023},
author = {Ozturk, M and Ozkaya, A and Karabas, L and Alagoz, C and Alkın, Z and Artunay, O and Bayramoglu, SE and Bolukbasi, S and Demir, G and Demir, M and Demircan, A and Erden, B and Erdogan, G and Erdogan, M and Eris, E and Kaldirim, H and Onur, &#x130;U and Osmanbasoğlu, OA and Erkul, SO and Perente, &#x130; and Sarici, K and Sayin, N and Yasa, D and Yilmaz, &#x130; and Yılmazabdurrahmanoglu, Z and , },
title = {Results of anti-VEGF treatment for neovascular AMD in eyes with different baseline visual acuity in Turkish population-based on real life data-Bosphorus retina study group.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {42},
number = {},
pages = {103640},
doi = {10.1016/j.pdpdt.2023.103640},
pmid = {37263398},
issn = {1873-1597},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab ; Vascular Endothelial Growth Factor A ; Treatment Outcome ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; *Photochemotherapy/methods ; Photosensitizing Agents/therapeutic use ; Retina ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Retrospective Studies ; },
abstract = {BACKGROUND: To investigate the anatomical and visual outcomes of the patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (anti-VEGF), according to the baseline best-corrected visual acuity (BCVA) based on the multicenter real-life data.<br><br>METHODS: Five-hundred-ninety patients who had taken the Pro Re Nata (PRN) treatment regimen with three loading doses and at least one year of follow-up were included. The patients were divided into three groups according to the baseline BCVA: Group 1 (BCVA&#xa0;&#x2265;&#xa0;1.3 Logmar), Group 2 (1.3 Logmar > BCVA&#xa0;&#x2265;&#xa0;0.3 Logmar), and Group 3 (BCVA&#xa0;&#x2264;&#xa0;0.2 Logmar). BCVA, central macular thickness (CMT), and the number of injections and visits were evaluated.<br><br>RESULTS: There were 175, 322, and 93 patients in Group 1, Group 2, and Group 3, respectively. The number of visits and injections in the 1st year was not different between the groups (p&#xa0;=&#xa0;0.58 and p&#xa0;=&#xa0;0.08) and was 7.09 and 4.41 (Group 1), 6.59 and 5.58 (Group 2), 6.77 and 4.08 (Group 3). There was a significant difference in CMT between the baseline and 12th month in Group 1 and Group 2 (p&#xa0;<&#xa0;0.001, p&#xa0;<&#xa0;0.001, respectively) but not in Group 3 (p&#xa0;=&#xa0;0.84). BCVA was significantly better in the 12th month in Group 1 (p&#xa0;<&#xa0;0.001), slightly worse in Group 2 (p&#xa0;=&#xa0;0.79), and significantly worse in Group 3 (p&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: This study provides evidence that an inadequate number of injections cannot protect vision. Moreover, it can cause vision loss, especially in the eyes with good vision.},
}
@article {pmid37259853,
year = {2023},
author = {Kumar, M and Singh, RP},
title = {WITHDRAWN: Pegcetacoplan in the treatment of geographic atrophy.},
journal = {Immunotherapy},
volume = {},
number = {},
pages = {},
doi = {10.2217/imt-2022-0263},
pmid = {37259853},
issn = {1750-7448},
abstract = {Ahead of Print article withdrawn by publisher.},
}
@article {pmid37259372,
year = {2023},
author = {Tseng, CH},
title = {The Risk of Age-Related Macular Degeneration Is Reduced in Type 2 Diabetes Patients Who Use Metformin.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {2},
pages = {},
pmid = {37259372},
issn = {1424-8247},
support = {MOST 103-2314-B-002-187-MY3//Ministry of Science and Technology/ ; },
abstract = {BACKGROUND: Whether metformin may reduce the risk of age-related macular degeneration (AMD) requires confirmation. This study compared the risk of AMD between ever users and never users of metformin matched on propensity score (PS) in Taiwanese patients with type 2 diabetes mellitus.<br><br>METHODS: We enrolled study subjects from Taiwan's National Health Insurance. A total of 423,949 patients with new onset diabetes from 1999 to 2005 were identified. After excluding ineligible patients and enrolling only patients aged between 50 and 79 years, we created 13,303 pairs of ever users and never users of metformin matched on PS. The patients were followed from 1 January 2006 to 31 December 2011. We estimated hazard ratios by Cox regression.<br><br>RESULTS: AMD was newly diagnosed in 506 ever users and 639 never users. The respective incidence rates (per 100,000 person-years) were 778.72 and 1016.62. The hazard ratio (HR) and 95% confidence interval (CI) for ever versus never users was 0.756 (0.673-0.850). While ever users were categorized by tertiles of cumulative duration (<31.8, 31.8-63.9 and >63.9 months) and cumulative dose (<947.1, 947.1-2193.5 and >2193.5 g) of metformin, a dose-response pattern was observed. For the respective tertiles of cumulative duration, the HRs (95% CIs) were 1.131 (0.961-1.330), 0.821 (0.697-0.967) and 0.464 (0.384-0.561), while compared to never users. For the respective tertiles of cumulative dose, the HRs (95% CIs) were 1.131 (0.962-1.329), 0.739 (0.624-0.876) and 0.525 (0.438-0.629). A risk reduction among ever users was observed for all tertiles of defined daily dose but was most remarkable for the third tertile with a defined daily dose of >0.64. Subgroup analyses suggested that the benefit of metformin could be similarly observed among men and women and for age subgroups of 50-64 and 65-79 years. However, patients with diabetic retinopathy would not be significantly benefited and metformin did not seem to be preventive for exudative AMD.<br><br>CONCLUSION: In general, metformin significantly reduces the risk of AMD.},
}
@article {pmid37259363,
year = {2023},
author = {Niu, Y and Zhang, G and Sun, X and He, S and Dou, G},
title = {Distinct Role of Lycium barbarum L. Polysaccharides in Oxidative Stress-Related Ocular Diseases.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {2},
pages = {},
pmid = {37259363},
issn = {1424-8247},
support = {81970814, 81670863//National Natural Science Foundation of China/ ; 2021JSTS28//clinical AFFMU foundation support/ ; },
abstract = {Oxidative stress is an imbalance between the increased production of reactive species and reduced antioxidant activity, which can cause a variety of disturbances including ocular diseases. Lycium barbarum polysaccharides (LBPs) are complex polysaccharides isolated from the fruit of L. barbarum, showing distinct roles in antioxidants. Moreover, it is relatively safe and non-toxic. In recent years, the antioxidant activities of LBPs have attracted remarkable attention. In order to illustrate its significance and underlying therapeutic value for vision, we comprehensively review the recent progress on the antioxidant mechanisms of LBP and its potential applications in ocular diseases, including diabetic retinopathy, hypertensive neuroretinopathy, age-related macular degeneration, retinitis pigmentosa, retinal ischemia/reperfusion injury, glaucoma, dry eye syndrome, and diabetic cataract.},
}
@article {pmid37259223,
year = {2023},
author = {Nouraeinejad, A},
title = {The Implication of Alu cDNA in the Pathogenesis of ARMD.},
journal = {Current aging science},
volume = {16},
number = {3},
pages = {168-169},
doi = {10.2174/1874609816666230530095410},
pmid = {37259223},
issn = {1874-6128},
mesh = {Humans ; DNA, Complementary/metabolism ; *Macular Degeneration/genetics ; Retinal Pigment Epithelium/metabolism/pathology ; },
abstract = {Age-related macular degeneration (ARMD or AMD) is a progressive, sight-threatening disease. The pathogenesis of ARMD is complex, involving many factors, such as metabolic, functional, genetic, and environmental factors. Recently, long interspersed nuclear element-1 (L1)- mediated reverse transcription (RT) of Alu RNA into cytoplasmic Alu complementary DNA (cDNA) has been associated with retinal pigment epithelium (RPE) destruction. These findings provide a strong input for a new direction in the management of ARMD, as certain human immunodeficiency virus (HIV) drugs, such as nucleoside reverse transcriptase inhibitors (NRTIs), were found to suppress inflammation and protect cells of the retina.},
}
@article {pmid37258659,
year = {2023},
author = {Montesel, A and Hagag, AM and Chandra, S and Muhammed, RP and Thottarath, S and Chandak, S and Sivaprasad, S},
title = {Quantitative response of macular neovascularisation to loading phase of aflibercept in neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {37},
number = {17},
pages = {3648-3655},
pmid = {37258659},
issn = {1476-5454},
mesh = {Humans ; Follow-Up Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Neovascularization, Pathologic/drug therapy ; Tomography, Optical Coherence/methods ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: To evaluate quantitative morphological changes in macular neovascularisation (MNV) network after aflibercept therapy in neovascular age-related macular degeneration (nAMD) patients.<br><br>METHODS: Consecutive treatment-na&#xef;ve patients with optical coherence tomography (OCT) angiography confirmed MNV due to nAMD who completed a loading phase of intravitreal aflibercept injections. A quantitative analysis of the vascular network remodelling was performed using a computational software (Angiotool).<br><br>RESULTS: A total of 53 eyes of 52 patients were included in the analysis. The total MNV area decreased significantly after three aflibercept injections (p&#x2009;=&#x2009;0.003). Total vessel area and vessel density decreased respectively of 20% and 12% at V3 (p&#x2009;<&#x2009;0.001 in both cases). Other parameters that reduced significantly were total vessel length, average vessel length and density of vascular junctions (p&#x2009;=&#x2009;0.018, p&#x2009;=&#x2009;0.002, and p&#x2009;=&#x2009;0.044, respectively). The number of vascular endpoints (p&#x2009;=&#x2009;0.001) and lacunarity (p&#x2009;=&#x2009;0.011) increased significantly, whilst the number of vascular junctions did not vary significantly (p&#x2009;=&#x2009;0.068). Changes in vascular metrics were predominantly driven by MNV type 1 and 2. No clear relationship was observed between any of the vascular metrics and the macular fluid status.<br><br>CONCLUSION: Although objective quantification of vascular parameters showed a significant remodelling of the MNV post-loading phase of aflibercept in type 1 and 2 MNV subtypes, none of the quantified vascular metrics correlated to the macular fluid response. These findings highlight a dissociation of anti-angiogenic and anti-permeability properties of aflibercept therapy during the loading phase.},
}
@article {pmid37256195,
year = {2023},
author = {Reitan, G and Kjellevold Haugen, IB and Andersen, K and Bragadottir, R and Bindesbøll, C},
title = {Through the Eyes of Patients: Understanding Treatment Burden of Intravitreal Anti-VEGF Injections for nAMD Patients in Norway.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1465-1474},
pmid = {37256195},
issn = {1177-5467},
abstract = {PURPOSE: Patients with neovascular age-related macular degeneration (nAMD) are treated with frequent intravitreal injections to maintain vision. The treatment frequency impacts the life of patients and caregivers and poses a major capacity challenge for Norwegian ophthalmic clinics. The purpose of this survey was to document patient-reported outcomes on how the disease and the treatment impact nAMD patients in Norway.<br><br>METHODS: Norwegian nAMD patients voluntarily completed the survey. The patients reported the time spent on each treatment appointment, the need for caregiver support, treatment intervals, and the emotional impact of the treatment. There was no active selection of patients to the survey. Respondents had to confirm the nAMD diagnosis prior to submitting the response. All data was included in the analysis as submitted by the respondents. This survey was market research involving anonymous patient data, and no participants were identifiable.<br><br>RESULTS: In total, 130 patients responded to the survey. The majority of patients reported to receive nine or more injections per year&#xa0;(48.8%), and many patients needed caregiver support for every treatment appointment (37.7%). Patients reported to be anxious one day (25.4%), two days (8.5%), one week (10.8%) or more than one week (3.1%) prior to treatment. The week before the treatment, 33.1% of patients reported to be stressed and 15.4% struggled to sleep. The majority of patients reported the treatment as uncomfortable (54.6%) or as somewhat painful (26.2%). The results on yearly number of injections, time used each treatment day and need for caregiver support suggested a variation between Norwegian hospital regions.<br><br>CONCLUSIONS: This survey uncovers how treatment with intravitreal injections represents a substantial burden for Norwegian patients with nAMD. Future research on how the treatment burden impacts nAMD patients may lead to more patient-centered care and help guide treatment decisions. New treatments with longer intervals between injections are likely to both reduce the treatment burden and improve capacity in ophthalmology clinics.},
}
@article {pmid37255600,
year = {2023},
author = {Feng, H and Chen, J and Zhang, Z and Lou, Y and Zhang, S and Yang, W},
title = {A bibliometric analysis of artificial intelligence applications in macular edema: exploring research hotspots and Frontiers.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1174936},
pmid = {37255600},
issn = {2296-634X},
abstract = {Background: Artificial intelligence (AI) is used in ophthalmological disease screening and diagnostics, medical image diagnostics, and predicting late-disease progression rates. We reviewed all AI publications associated with macular edema (ME) research Between 2011 and 2022 and performed modeling, quantitative, and qualitative investigations. Methods: On 1st February 2023, we screened the Web of Science Core Collection for AI applications related to ME, from which 297 studies were identified and analyzed (2011-2022). We collected information on: publications, institutions, country/region, keywords, journal name, references, and research hotspots. Literature clustering networks and Frontier knowledge bases were investigated using bibliometrix-BiblioShiny, VOSviewer, and CiteSpace bibliometric platforms. We used the R "bibliometrix" package to synopsize our observations, enumerate keywords, visualize collaboration networks between countries/regions, and generate a topic trends plot. VOSviewer was used to examine cooperation between institutions and identify citation relationships between journals. We used CiteSpace to identify clustering keywords over the timeline and identify keywords with the strongest citation bursts. Results: In total, 47 countries published AI studies related to ME; the United States had the highest H-index, thus the greatest influence. China and the United States cooperated most closely between all countries. Also, 613 institutions generated publications - the Medical University of Vienna had the highest number of studies. This publication record and H-index meant the university was the most influential in the ME field. Reference clusters were also categorized into 10 headings: retinal Optical Coherence Tomography (OCT) fluid detection, convolutional network models, deep learning (DL)-based single-shot predictions, retinal vascular disease, diabetic retinopathy (DR), convolutional neural networks (CNNs), automated macular pathology diagnosis, dry age-related macular degeneration (DARMD), class weight, and advanced DL architecture systems. Frontier keywords were represented by diabetic macular edema (DME) (2021-2022). Conclusion: Our review of the AI-related ME literature was comprehensive, systematic, and objective, and identified future trends and current hotspots. With increased DL outputs, the ME research focus has gradually shifted from manual ME examinations to automatic ME detection and associated symptoms. In this review, we present a comprehensive and dynamic overview of AI in ME and identify future research areas.},
}
@article {pmid37254103,
year = {2023},
author = {Peng, ET and Adrean, SD},
title = {Geographic Atrophy after Reabsorption of Pigment Epithelial Detachment (GARPED) study.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {242},
pmid = {37254103},
issn = {1471-2415},
mesh = {Humans ; Aged, 80 and over ; *Geographic Atrophy/diagnosis/etiology ; *Macular Degeneration/diagnosis ; Retinal Pigment Epithelium/pathology ; Follow-Up Studies ; *Retinal Detachment/diagnosis/etiology/drug therapy ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; },
abstract = {BACKGROUND: To describe the occurrence, rate of geographic atrophy (GA) expansion, and changes in visual acuity (VA) after reabsorption of subfoveal pigment epithelial detachments (PED).<br><br>METHODS: Included patients had reabsorption of a PED followed by GA. Patients underwent clinical examination with SD-OCT. Images were classified by size with grading occurring post reabsorption. VA was recorded pre-reabsorption, post-reabsorption, and over time.<br><br>RESULTS: The average age of the cohort, consisting of 22 eyes from 19 participants, was 86.9&#xa0;years at reabsorption. Prior to reabsorption, the VA was 20/80 and then declined to 20/200 (p&#x2009;=&#x2009;0.001) with an average follow-up time of 30.2&#xa0;months. There was no significant VA change after the initial loss with reabsorption. The average initial lesion size of GA was 0.987 mm[2] with an average growth rate of 0.274&#xa0;mm/year.<br><br>CONCLUSIONS: This study longitudinally examined GA growth rate in patients with reabsorbed PEDs. These patients started with a drusenoid or serous PED, had a dramatic reduction in vision and GA that occurred in place of the PED. These GA lesions have a slower growth rate and a smaller area of onset compared to rates previously reported in the literature. They do not show significant VA change after reabsorption. As we have entered the era of GA therapy, these patients may not benefit from current treatments.},
}
@article {pmid37253802,
year = {2023},
author = {Mukai, R and Kataoka, K and Tanaka, K and Miyara, Y and Maruko, I and Nakayama, M and Watanabe, Y and Yamamoto, A and Wakatsuki, Y and Onoe, H and Wakugawa, S and Terao, N and Hasegawa, T and Hashiya, N and Kawai, M and Maruko, R and Itagaki, K and Honjo, J and Okada, AA and Mori, R and Koizumi, H and Iida, T and Sekiryu, T},
title = {Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {8747},
pmid = {37253802},
issn = {2045-2322},
mesh = {Humans ; Angiogenesis Inhibitors/adverse effects ; Retrospective Studies ; Japan ; *Choroidal Neovascularization/drug therapy ; *Wet Macular Degeneration/drug therapy ; Intravitreal Injections ; Tomography, Optical Coherence ; Fluorescein Angiography ; },
abstract = {This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues.},
}
@article {pmid37253747,
year = {2023},
author = {Gjølberg, TT and Wik, JA and Johannessen, H and Krüger, S and Bassi, N and Christopoulos, PF and Bern, M and Foss, S and Petrovski, G and Moe, MC and Haraldsen, G and Fosse, JH and Skålhegg, BS and Andersen, JT and Sundlisæter, E},
title = {Antibody blockade of Jagged1 attenuates choroidal neovascularization.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {3109},
pmid = {37253747},
issn = {2041-1723},
mesh = {Humans ; Mice ; Animals ; *Vascular Endothelial Growth Factor A/metabolism ; Endothelial Cells/metabolism ; *Choroidal Neovascularization/pathology ; Antibodies, Blocking/therapeutic use ; Signal Transduction/physiology ; Disease Models, Animal ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Antibody-based blocking of vascular endothelial growth factor (VEGF) reduces choroidal neovascularization (CNV) and retinal edema, rescuing vision in patients with neovascular age-related macular degeneration (nAMD). However, poor response and resistance to anti-VEGF treatment occurs. We report that targeting the Notch ligand Jagged1 by a monoclonal antibody reduces neovascular lesion size, number of activated phagocytes and inflammatory markers and vascular leakage in an experimental CNV mouse model. Additionally, we demonstrate that Jagged1 is expressed in mouse and human eyes, and that Jagged1 expression is independent of VEGF signaling in human endothelial cells. When anti-Jagged1 was combined with anti-VEGF in mice, the decrease in lesion size exceeded that of either antibody alone. The therapeutic effect was solely dependent on blocking, as engineering antibodies to abolish effector functions did not impair the therapeutic effect. Targeting of Jagged1 alone or in combination with anti-VEGF may thus be an attractive strategy to attenuate CNV-bearing diseases.},
}
@article {pmid37252731,
year = {2023},
author = {Sharma, D and Zachary, I and Jia, H},
title = {Mechanisms of Acquired Resistance to Anti-VEGF Therapy for Neovascular Eye Diseases.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {5},
pages = {28},
pmid = {37252731},
issn = {1552-5783},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Ranibizumab/therapeutic use ; Bevacizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {PURPOSE: The purpose of this study was to evaluate clinical reports of response-loss in patients with neovascular eye diseases, such as neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME), after repeated anti-vascular endothelial growth factor (VEGF) therapy. To assess experimental evidence of associations of other angiogenic growth factors and endothelial glycolytic pathways with the diseases and to propose the underlying mechanisms.<br><br>METHODS: Review of published clinical studies and experimental investigations.<br><br>RESULTS: Intravitreal injection of anti-VEGF biologic drugs (e.g. bevacizumab, ranibizumab, and aflibercept) is the front-line treatment for neovascular AMD and DME, and acts by halting the progression of excess blood vessel growth and leakage. Despite favorable clinical results, exudation returns in a number of patients after repeated administrations over time. Patients suffering from disease recurrence may have developed an acquired resistance to anti-VEGF therapy. We have analyzed clinical and preclinical findings on changes to angiogenic signaling pathways following VEGF-targeted treatment and hypothesize that switching to alternative pathways could potentially bypass VEGF blockade, accounting for development of resistance to anti-VEGF therapy. We have also discussed potential reprogramming of ocular endothelial glycolysis in response to VEGF antagonism and proposed that metabolic adaptations could impair blood-retinal barrier function, counteracting the clinical efficacy of VEGF-targeted therapies and contributing to a decline of response to them.<br><br>CONCLUSIONS: Future studies of the mechanisms proposed in this review may shed some light on how these adaptations result in the development of acquired resistance to anti-VEGF therapy, which should help discover new therapeutic strategies for overcoming anti-VEGF resistance and improving clinical efficacy.},
}
@article {pmid37252721,
year = {2023},
author = {Wang, E and Kalloniatis, M and Ly, A},
title = {Effective health communication for age-related macular degeneration: An exploratory qualitative study.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {43},
number = {5},
pages = {1278-1293},
doi = {10.1111/opo.13168},
pmid = {37252721},
issn = {1475-1313},
mesh = {Humans ; *Health Communication ; *Macular Degeneration/diagnosis/therapy ; Qualitative Research ; Vision Disorders ; Focus Groups ; Blindness ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a major cause of vision loss globally. Patients with AMD may not always understand or retain the information about AMD communicated by their eyecare practitioner. This study aims to explore the characteristics of effective health communication for AMD, from both patients' and eyecare practitioners' perspectives. The purpose is to provide a foundation for understanding how health communication for AMD could potentially be improved in the future.<br><br>METHODS: A total of 10 focus groups involving 17 patients with AMD and 17 optometrists were conducted via web conferencing. Each session was audio-recorded, transcribed and analysed using the Grounded Theory Methodology.<br><br>RESULTS: The five themes identified are as follows: (1) materials' quality, (2) materials' relevance, (3) contextualising for the individual, (4) contextualising for the disease and (5) support network. Participants expressed concern about the unrealistic yet common depiction of vision loss in AMD as a black patch overlying common visual scenes. They also preferred education materials tailored to a specific disease stage and the regular opportunity to ask or answer questions. Longer appointment durations and peer support (from family, friends or others with AMD) were also valued.<br><br>CONCLUSION: Optometrists are encouraged to focus on three over-arching dimensions when counselling patients with AMD in routine clinical practice: (1) curating and using disease and stage-specific, impactful education materials, (2) their chairside verbal communication techniques and (3) AMD-specific opportunities for care coordination among patient family and friends, peers and other multidisciplinary members of the care support team.},
}
@article {pmid37249901,
year = {2023},
author = {Wang, Y and Liang, Y and Seth, I and Wu, G and Du, Z and Huang, Y and Shang, X and Liu, S and Hu, Y and Fang, Y and Zhu, Z and Hu, Y and Zhang, X and Yang, X and Yu, H},
title = {Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {3},
pages = {293-302},
doi = {10.1097/APO.0000000000000612},
pmid = {37249901},
issn = {2162-0989},
mesh = {Male ; Humans ; Middle Aged ; Female ; *Cardiovascular Diseases/epidemiology ; Prospective Studies ; Biological Specimen Banks ; *Atherosclerosis/complications/epidemiology ; Risk Factors ; Vitamin D ; *Macular Degeneration/epidemiology ; United Kingdom/epidemiology ; },
abstract = {PURPOSE: Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD).<br><br>METHODS: Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality.<br><br>RESULTS: We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10&#x2002;U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, Pnonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (Pnonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD.<br><br>CONCLUSIONS: Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.},
}
@article {pmid37249566,
year = {2023},
author = {Dey, S and Catchpole, T and Takacs, A and Csaky, KG},
title = {Investigating the effects of 7-ketocholesterol on retinal pigment epithelium bioenergetics.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {37},
number = {7},
pages = {e23002},
doi = {10.1096/fj.202300101R},
pmid = {37249566},
issn = {1530-6860},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; Retina/metabolism ; Energy Metabolism ; *Macular Degeneration/metabolism ; Adenosine Triphosphate/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is associated with formation of drusen, clusters of lipids, and oxidized lipid products under the retinal pigment epithelium (RPE). 7-Ketocholesterol (7KC) is a form of oxidized cholesterol present in drusen and is hypothesized to play a role in AMD pathogenesis. The association of 7KC with cellular toxicity and inflammation, key elements of AMD pathology, has been demonstrated. However, the effects of 7KC on altering RPE bioenergetics, a potentially important pathologic process in AMD, are unclear. Herein, we describe the effects of non-lethal doses of 7KC on the bioenergetics and phenotype of RPE cells in culture. Metabolic analysis demonstrated a significant dose-dependent increase in total ATP production rates that was driven primarily by an increase in glycolysis. The increase in glycolysis was accompanied by an increase in glucose uptake and increased expression of hexokinase 1. Increased levels of Translocase of Outer Mitochondrial Membrane 20 and NADH:Ubiquinone Oxidoreductase Core Subunit S1, Succinate dehydrogenase, Ubiquinol-Cytochrome C Reductase Core Protein 2, Cytochrome C Oxidase II, and ATP synthase subunit beta, proteins involved in oxidative phosphorylation (OXPHOS), were also seen. However, specific electron transport chain activity remained unchanged. 7KC-treated cells also demonstrated a change in cellular morphology with decreased expression of epithelial markers. In summary, 7KC has significant effects on the bioenergetics and morphology of RPE cells reflective of findings seen in clinical AMD.},
}
@article {pmid37248127,
year = {2023},
author = {Auger, A and Khanna, RK and Bonicel, P and Pisella, PJ and Le Lez, ML},
title = {[Impact of the French 2020 COVID-19 lockdown on the treatment and follow-up of patients with exudative age-related macular degeneration].},
journal = {Journal francais d'ophtalmologie},
volume = {46},
number = {6},
pages = {596-604},
doi = {10.1016/j.jfo.2022.11.014},
pmid = {37248127},
issn = {1773-0597},
mesh = {Humans ; Infant ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab ; Follow-Up Studies ; Retrospective Studies ; *COVID-19/epidemiology/prevention &amp; control ; Communicable Disease Control ; *Macular Degeneration/drug therapy/epidemiology ; Intravitreal Injections ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/epidemiology ; },
abstract = {PURPOSE: To assess the impact of the measures taken during the lockdown period from March 17 to May 11, 2020 on the management of patients with exudative age related macular degeneration treated by intravitreal anti-VEGF injections at the University Hospital of Tours.<br><br>METHODS: In this retrospective study, patients were included after analysis of the computerized medical records of patients with age related macular degeneration. Those who were treated for exudative age related macular degeneration who received at least 1 intravitreal injection in the 12 months prior and at least one consultation in the 6 months prior to the lockdown period, were included. The initial and final mean visual acuity were compared with a 5 letter non-inferiority margin. A subgroup analysis was performed according to outcomes. The visual acuities immediately after this period were also recorded.<br><br>RESULTS: In all, 595 eyes of 493 patients were included. The mean initial visual acuity was 59.6 letters, vs. 58.5 for the final visual acuity, i.e. a difference of -1.13 letters with a lower limit of the confidence interval of less than 5. The visual acuity on release from lockdown was comparable to the other 2 measurements. Initial visual acuity and the number of missed treatments were the main factors associated with functional loss.<br><br>CONCLUSION: Patients' visual acuity during the lockdown period was able to be maintained despite the restrictive measures and limitation of care access in France. The most common cause of substantial visual decline was missed intravitreal injections.},
}
@article {pmid37247185,
year = {2024},
author = {Gökce, SE and Çelik, A and Başkan, C},
title = {The role of blood neutrophil lymphocyte ratio in predicting the initial response to anti-VEGF treatment in neovascular AMD patients.},
journal = {Irish journal of medical science},
volume = {193},
number = {1},
pages = {517-521},
pmid = {37247185},
issn = {1863-4362},
mesh = {Humans ; Middle Aged ; Aged ; Bevacizumab ; *Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Neutrophils ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Treatment Outcome ; },
abstract = {PURPOSE: Vascular endothelial growth factor (VEGF) has a critical role in age-related macular degeneration (AMD), and intravitreal injection of anti-VEGF drugs is the mainstay of neovascular AMD treatment. Blood neutrophil-to-lymphocyte ratio (NLR) is shown to be a biomarker of inflammation in AMD. We aimed to investigate the role of NLR in predicting favorable short-term anti-VEGF treatment results in neovascular AMD patients.<br><br>METHODS: A total of 112 patients diagnosed with exudative AMD and had taken 3 monthly intravitreal bevacizumab injections were analyzed retrospectively. Medical records were reached to obtain neutrophil and lymphocyte values to calculate NLR. Best-corrected visual acuity and central macular thickness (CMT) measurements were recorded at each visit. T test or Mann-Whitney U test was used to compare continuous variables, and chi-square test was used to compare categorical variables. Receiver operating characteristics curve (ROC) analysis was performed to determine cut-off, sensitivity, and specificity values. P value of&#x2009;&#x2264;&#x2009;0.05 was considered statistically significant.<br><br>RESULTS: The mean age was 68.1&#x2009;&#xb1;&#x2009;7.2&#xa0;years, and the mean NLR was 2.11&#x2009;&#xb1;&#x2009;0.81. The ROC analysis revealed a cut off value of 2.0 for NLR to predict at least 100&#xa0;&#x3bc;m CMT change (sensitivity 87.1%; specificity 87.8%) and a cut off value of 2.4 for NLR to predict at least 0.1 logMAR visual improvement (sensitivity 77.2%; specificity 64.8%) after 3 monthly IVT bevacizumab injections.<br><br>CONCLUSION: NLR can provide additional prognostic information for the identification of patients with a good initial response to anti-VEGF therapy.},
}
@article {pmid37246918,
year = {2023},
author = {He, S and Bulloch, G and Zhang, L and Xie, Y and Wu, W and He, Y and Meng, W and Shi, D and He, M},
title = {Cross-camera Performance of Deep Learning Algorithms to Diagnose Common Ophthalmic Diseases: A Comparative Study Highlighting Feasibility to Portable Fundus Camera Use.},
journal = {Current eye research},
volume = {48},
number = {9},
pages = {857-863},
doi = {10.1080/02713683.2023.2215984},
pmid = {37246918},
issn = {1460-2202},
mesh = {Humans ; Adolescent ; Adult ; *Deep Learning ; Feasibility Studies ; *Glaucoma/diagnosis ; *Optic Nerve Diseases/diagnosis ; Algorithms ; *Diabetic Retinopathy/diagnosis ; *Macular Degeneration/diagnosis ; Photography/methods ; },
abstract = {PURPOSE: To compare the inter-camera performance and consistency of various deep learning (DL) diagnostic algorithms applied to fundus images taken from desktop Topcon and portable Optain cameras.<br><br>METHODS: Participants over 18&#x2009;years of age were enrolled between November 2021 and April 2022. Pair-wise fundus photographs from each patient were collected in a single visit; once by Topcon (used as the reference camera) and once by a portable Optain camera (the new target camera). These were analyzed by three previously validated DL models for the detection of diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucomatous optic neuropathy (GON). Ophthalmologists manually analyzed all fundus photos for the presence of DR and these were referred to as the ground truth. Sensitivity, specificity, the area under the curve (AUC) and agreement between cameras (estimated by Cohen's weighted kappa, K) were the primary outcomes of this study.<br><br>RESULTS: A total of 504 patients were recruited. After excluding 12 photographs with matching errors and 59 photographs with low quality, 906 pairs of Topcon-Optain fundus photos were available for algorithm assessment. Topcon and Optain cameras had excellent consistency (&#x39a;=0.80) when applied to the referable DR algorithm, while AMD had moderate consistency (&#x39a;=0.41) and GON had poor consistency (&#x39a;=0.32). For the DR model, Topcon and Optain achieved a sensitivity of 97.70% and 97.67% and a specificity of 97.92% and 97.93%, respectively. There was no significant difference between the two camera models (McNemar's test: x[2]=0.08, p&#x2009;=&#x2009;.78).<br><br>CONCLUSION: Topcon and Optain cameras had excellent consistency for detecting referable DR, albeit performances for detecting AMD and GON models were unsatisfactory. This study highlights the methods of using pair-wise images to evaluate DL models between reference and new fundus cameras.},
}
@article {pmid37246110,
year = {2023},
author = {Mondéjar, J and Pellico, G and Sallén, T and Núñez, P and Puigcerver, M and Pallàs, I},
title = {[Management optimization of neovascular age-related macular degeneration in Spain: Evolution towards proactive treatment models].},
journal = {Journal of healthcare quality research},
volume = {38},
number = {5},
pages = {284-293},
doi = {10.1016/j.jhqr.2023.02.007},
pmid = {37246110},
issn = {2603-6479},
mesh = {Humans ; Spain ; *Delivery of Health Care ; Hospitals ; *Macular Degeneration/therapy/diagnosis ; },
abstract = {INTRODUCTION AND OBJECTIVE: Healthcare resources optimization is crucial to assume the growing demand of neovascular age-related macular degeneration (nAMD). This work provides guidelines and support so that each hospital can lead its change management.<br><br>METHODS: The OPTIMUS project (n=10 hospitals) was based on face-to-face interviews with the key staff of the ophthalmology services, and alignment with the main responsible for each centre (nominal group) to identify potential needs for improving nAMD. The OPTIMUS nominal group was expanded to 12 centres (eVOLUTION). Through different remote work sessions, different guides and tools were defined and developed to implement proactive treatment strategies, one-step treatment administration and potential for remote visits (eConsult) in nAMD.<br><br>RESULTS: The information collected from the OPTIMUS interviews and working groups (n=10 centres) defined roadmaps to promote the development of protocols and proactive treatment strategies, including healthcare workload optimization and one-stop treatment administration in nAMD. With eVOLUTION, processes and tools were developed to promote eConsult: (i) healthcare burden calculator; (ii) definition of potential patients for telematic management; (iii) definition of nAMD management archetypes; (iv) definition of processes for implementation of eConsult by archetype; and (v) key performance indicators for changing evaluation.<br><br>CONCLUSIONS: Managing change is an internal task that requires an adequate diagnosis of processes and feasible implementation roadmaps. OPTIMUS and eVOLUTION provide the basic tools for an autonomous advance of hospitals in the optimization of AMD management, with the available resources.},
}
@article {pmid37245779,
year = {2023},
author = {Dubowsky, JG and Estevez, JJ and Craig, JE and Appukuttan, B and Carr, JM},
title = {Disease profiles in the Indigenous Australian population are suggestive of a common complement control haplotype.},
journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases},
volume = {112},
number = {},
pages = {105453},
doi = {10.1016/j.meegid.2023.105453},
pmid = {37245779},
issn = {1567-7257},
mesh = {Humans ; Haplotypes ; *Australian Aboriginal and Torres Strait Islander Peoples ; Australia/epidemiology ; Chronic Disease ; },
abstract = {Aboriginal and Torres Strait Islander People (respectfully referred to as Indigenous Australians herein) are disparately burdened by many infectious and chronic diseases relative to Australians with European genetic ancestry. Some of these diseases are described in other populations to be influenced by the inherited profile of complement genes. These include complement factor B, H, I and complement factor H-related (CFHR) genes that can contribute to a polygenic complotype. Here the focus is on the combined deletion of CFHR1 and 3 to form a common haplotype (CFHR3-1Δ). The prevalence of CFHR3-1Δ is high in people with Nigerian and African American genetic ancestry and correlates to a higher frequency and severity of systemic lupus erythematosus (SLE) but a lower prevalence of age-related macular degeneration (AMD) and IgA-nephropathy (IgAN). This pattern of disease is similarly observed among Indigenous Australian communities. Additionally, the CFHR3-1Δ complotype is also associated with increased susceptibility to infection with pathogens, such as Neisseria meningitidis and Streptococcus pyogenes, which also have high incidences in Indigenous Australian communities. The prevalence of these diseases, while likely influenced by social, political, environmental and biological factors, including variants in other components of the complement system, may also be suggestive of the CFHR3-1Δ haplotype in Indigenous Australians. These data highlight a need to define the Indigenous Australian complotypes, which may lead to the discovery of new risk factors for common diseases and progress towards precision medicines for treating complement-associated diseases in Indigenous and non-Indigenous populations. Herein, the disease profiles suggestive of a common complement CFHR3-1Δ control haplotype are examined.},
}
@article {pmid37244451,
year = {2023},
author = {Sahoo, M and Mitra, M and Pal, S},
title = {Improved detection of dry age-related macular degeneration from optical coherence tomography images using adaptive window based feature extraction and weighted ensemble based classification approach.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {42},
number = {},
pages = {103629},
doi = {10.1016/j.pdpdt.2023.103629},
pmid = {37244451},
issn = {1873-1597},
mesh = {Humans ; Aged ; *Macular Degeneration/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Photochemotherapy/methods ; Photosensitizing Agents ; Retina ; },
abstract = {BACKGROUND: Dry Age-related macular degeneration (AMD), which affects the older population, can lead to blindness when left untreated. Preventing vision loss in elderly needs early identification. Dry-AMD diagnosis is still time-consuming and very subjective, depending on the ophthalmologist. Setting up a thorough eye-screening system to find Dry-AMD is a very difficult task.<br><br>METHODOLOGY: This study aims to develop a weighted majority voting (WMV) ensemble-based prediction model to diagnose Dry-AMD. The WMV approach combines the predictions from base-classifiers and chooses the class with greatest vote based on assigned weights to each classifier. A novel feature extraction method is used along the retinal pigment epithelium (RPE) layer, with the number of windows calculated for each picture playing an important part in identifying Dry-AMD/normal images using the WMV methodology. Pre-processing using hybrid-median filter followed by scale-invariant feature transform based segmentation of RPE layer and curvature flattening of retina is employed to measure exact thickness of RPE layer.<br><br>RESULT: The proposed model is trained on 70% of the OCT image database (OCTID) and evaluated on remaining OCTID and SD-OCT Noor dataset. Model has achieved accuracy of 96.15% and 96.94%, respectively. The suggested algorithm's effectiveness in Dry-AMD identification is demonstrated by comparison with alternative approaches. Even though the suggested model is only trained on the OCTID, it has performed well when tested on additional dataset.<br><br>CONCLUSION: The suggested architecture can be used for quick eye-screening for early identification of Dry-AMD. The recommended method may be applied in real-time since it requires fewer complexity and learning-variables.},
}
@article {pmid37243434,
year = {2023},
author = {Yoon, JM and Lim, DH and Youn, J and Han, K and Kim, BS and Jung, W and Yeo, Y and Shin, DW and Ham, DI},
title = {Increased risk of Parkinson's disease amongst patients with age-related macular degeneration and visual disability: A nationwide cohort study.},
journal = {European journal of neurology},
volume = {30},
number = {9},
pages = {2641-2649},
doi = {10.1111/ene.15896},
pmid = {37243434},
issn = {1468-1331},
mesh = {Humans ; Cohort Studies ; *Disease Susceptibility ; *Macular Degeneration/epidemiology ; *Parkinson Disease/epidemiology ; Proportional Hazards Models ; Republic of Korea/epidemiology ; Risk Factors ; *Blindness/epidemiology ; National Health Programs ; Middle Aged ; Aged ; Routinely Collected Health Data ; Male ; Female ; Incidence ; Regression Analysis ; Comorbidity ; },
abstract = {BACKGROUND AND PURPOSE: The association between Parkinson's disease (PD) and age-related macular degeneration (AMD) has been shown in previous reports. However, the association between the severity of AMD and PD development is unknown. The aim was to evaluate the association of AMD with/without visual disability (VD) with the risk of PD occurrence using the National Health Insurance data in South Korea.<br><br>METHODS: A total of 4,205,520 individuals, 50&#x2009;years or older and without a previous diagnosis of PD, participated in the Korean National Health Screening Program in 2009. AMD was verified using diagnostic codes, and participants with VD were defined as those with loss of vision or visual field defect as certified by the Korean Government. The participants were followed up until 31 December 2019, and incident cases of PD were identified using registered diagnostic codes. The hazard ratio was calculated for groups (control and AMD with/without VD) using multivariable adjusted Cox regression analysis.<br><br>RESULTS: In total, 37,507 participants (0.89%) were diagnosed with PD. Amongst individuals with AMD, the risk of PD development was higher in individuals with VD (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.09-1.67) than in those without (aHR 1.22, 95% CI 1.15-1.30) compared with controls. Additionally, an increased risk of PD was observed in individuals with AMD compared with controls, regardless of the presence of VD (aHR 1.23, 95% CI 1.16-1.31).<br><br>CONCLUSIONS: Visual disability in AMD was associated with the development of PD. This suggests that neurodegeneration in PD and AMD may have common pathways.},
}
@article {pmid37242726,
year = {2023},
author = {Rafael, D and Guerrero, M and Marican, A and Arango, D and Sarmento, B and Ferrer, R and Durán-Lara, EF and Clark, SJ and Schwartz, S},
title = {Delivery Systems in Ocular Retinopathies: The Promising Future of Intravitreal Hydrogels as Sustained-Release Scaffolds.},
journal = {Pharmaceutics},
volume = {15},
number = {5},
pages = {},
pmid = {37242726},
issn = {1999-4923},
support = {project N&#xba; 1210476//ANID FONDECYT Regular (Chile)/ ; GRC - 2021 SGR 1173//Ag&#xe8;ncia de gesti&#xf3; d'ajuts universitaris i de recerca (AGAUR)- Departament recreca i universitats, Generalitat de Catalunya, Spain./ ; },
abstract = {Slow-release delivery systems are needed to ensure long-term sustained treatments for retinal diseases such as age-related macular degeneration and diabetic retinopathy, which are currently treated with anti-angiogenic agents that require frequent intraocular injections. These can cause serious co-morbidities for the patients and are far from providing the adequate drug/protein release rates and required pharmacokinetics to sustain prolonged efficacy. This review focuses on the use of hydrogels, particularly on temperature-responsive hydrogels as delivery vehicles for the intravitreal injection of retinal therapies, their advantages and disadvantages for intraocular administration, and the current advances in their use to treat retinal diseases.},
}
@article {pmid37242701,
year = {2023},
author = {Sharma, A and Singh, NK},
title = {Long Non-Coding RNAs and Proliferative Retinal Diseases.},
journal = {Pharmaceutics},
volume = {15},
number = {5},
pages = {},
pmid = {37242701},
issn = {1999-4923},
support = {EY029709/EY/NEI NIH HHS/United States ; P30EY04068/EY/NEI NIH HHS/United States ; },
abstract = {Retinopathy refers to disorders that affect the retina of the eye, which are frequently caused by damage to the retina's vascular system. This causes leakage, proliferation, or overgrowth of blood vessels through the retina, which can lead to retinal detachment or breakdown, resulting in vision loss and, in rare cases, blindness. In recent years, high-throughput sequencing has significantly hastened the discovery of new long non-coding RNAs (lncRNAs) and their biological functions. LncRNAs are rapidly becoming recognized as critical regulators of several key biological processes. Current breakthroughs in bioinformatics have resulted in the identification of several lncRNAs that may have a role in retinal disorders. Nevertheless, mechanistic investigations have yet to reveal the relevance of these lncRNAs in retinal disorders. Using lncRNA transcripts for diagnostic and/or therapeutic purposes may aid in the development of appropriate treatment regimens and long-term benefits for patients, as traditional medicines and antibody therapy only provide temporary benefits that must be repeated. In contrast, gene-based therapies can provide tailored, long-term treatment solutions. Here, we will discuss how different lncRNAs affect different retinopathies, including age-related macular degeneration (AMD), diabetic retinopathy (DR), central retinal vein occlusion (CRVO), proliferative vitreoretinopathy (PVR), and retinopathy of prematurity (ROP), which can cause visual impairment and blindness, and how these retinopathies can be identified and treated using lncRNAs.},
}
@article {pmid37242658,
year = {2023},
author = {Veritti, D and Sarao, V and Di Bin, F and Lanzetta, P},
title = {Pharmacokinetic and Pharmacodynamic Rationale for Extending VEGF Inhibition Increasing Intravitreal Aflibercept Dose.},
journal = {Pharmaceutics},
volume = {15},
number = {5},
pages = {},
pmid = {37242658},
issn = {1999-4923},
abstract = {BACKGROUND: The effects of various dosages and treatment regimens on intravitreal aflibercept concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF were evaluated using a drug and disease assessment model. The 8 mg dosage received specific attention.<br><br>METHODS: A time-dependent mathematical model was developed and implemented using Wolfram Mathematica software v12.0. This model was used to obtain drug concentrations after multiple doses of different aflibercept dosages (0.5 mg, 2 mg, and 8 mg) and to estimate the time-dependent intravitreal free VEGF percentage levels. A series of fixed treatment regimens were modeled and evaluated as potential clinical applications.<br><br>RESULTS: The simulation results indicate that 8 mg aflibercept administered at a range of treatment intervals (between 12 and 15 weeks) would allow for the proportion of free VEGF to remain below threshold levels. Our analysis indicates that these protocols maintain the ratio of free VEGF below 0.001%.<br><br>CONCLUSIONS: Fixed q12-q15 (every 12-15 weeks) 8 mg aflibercept regimens can produce adequate intravitreal VEGF inhibition.},
}
@article {pmid37242655,
year = {2023},
author = {Ferro Desideri, L and Traverso, CE and Nicolò, M and Munk, MR},
title = {Faricimab for the Treatment of Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.},
journal = {Pharmaceutics},
volume = {15},
number = {5},
pages = {},
pmid = {37242655},
issn = {1999-4923},
abstract = {Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients and long-term visual acuity decline due to complications such as macular atrophy and fibrosis. Targeting the angiopoietin/Tie (Ang/Tie) pathway beyond the VEGF pathway may be a possible therapeutic strategy; which may has the potential to solve some of the previous mentioned challenges. Faricimab is a new; bispecific antibody targeting both VEGF-A and the Ang-Tie/pathway. It was approved by FDA and; more recently; by EMA for treating w-AMD and DME. Results from phase III trials TENAYA and LUCERNE (w-AMD) and RHINE and YOSEMITE (DME) have shown the potential of faricimab to maintain clinical efficacy with more prolonged treatment regimens compared to aflibercept (12 or 16 weeks) with a a good safety profile.},
}
@article {pmid37242572,
year = {2023},
author = {Abedin Zadeh, M and Alany, RG and Satarian, L and Shavandi, A and Abdullah Almousa, M and Brocchini, S and Khoder, M},
title = {Maillard Reaction Crosslinked Alginate-Albumin Scaffolds for Enhanced Fenofibrate Delivery to the Retina: A Promising Strategy to Treat RPE-Related Dysfunction.},
journal = {Pharmaceutics},
volume = {15},
number = {5},
pages = {},
pmid = {37242572},
issn = {1999-4923},
abstract = {There are limited treatments currently available for retinal diseases such as age-related macular degeneration (AMD). Cell-based therapy holds great promise in treating these degenerative diseases. Three-dimensional (3D) polymeric scaffolds have gained attention for tissue restoration by mimicking the native extracellular matrix (ECM). The scaffolds can deliver therapeutic agents to the retina, potentially overcoming current treatment limitations and minimizing secondary complications. In the present study, 3D scaffolds made up of alginate and bovine serum albumin (BSA) containing fenofibrate (FNB) were prepared by freeze-drying technique. The incorporation of BSA enhanced the scaffold porosity due to its foamability, and the Maillard reaction increased crosslinking degree between ALG with BSA resulting in a robust scaffold with thicker pore walls with a compression modulus of 13.08 KPa suitable for retinal regeneration. Compared with ALG and ALG-BSA physical mixture scaffolds, ALG-BSA conjugated scaffolds had higher FNB loading capacity, slower release of FNB in the simulated vitreous humour and less swelling in water and buffers, and better cell viability and distribution when tested with ARPE-19 cells. These results suggest that ALG-BSA MR conjugate scaffolds may be a promising option for implantable scaffolds for drug delivery and retinal disease treatment.},
}
@article {pmid37242430,
year = {2023},
author = {Paramaswaran, Y and Subramanian, A and Paramakrishnan, N and Ramesh, M and Muthuraman, A},
title = {Therapeutic Investigation of Palm Oil Mill Effluent-Derived Beta-Carotene in Streptozotocin-Induced Diabetic Retinopathy via the Regulation of Blood-Retina Barrier Functions.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {5},
pages = {},
pmid = {37242430},
issn = {1424-8247},
support = {FRGS/1/2021/SKK0/AIMST/03/4//Malaysian Ministry of Education through Fundamental Research Grant Scheme/ ; },
abstract = {Diabetic retinopathy (DR) primarily progresses into retinal degeneration caused by microvascular dysfunction. The pathophysiology of DR progression is still uncertain. This study investigates the function of beta-carotene (PBC) originating from palm oil mill effluent in the treatment of diabetes in mice. An intraperitoneal injection of streptozotocin (35 mg/kg) was used to induce diabetes, which was then accelerated by an intravitreal (i.vit.) injection of STZ (20 µL on day 7). PBC (50 and 100 mg/kg) and dexamethasone (DEX: 10 mg/kg) were also administered orally (p.o.) for 21 days. At various time intervals, the optomotor response (OMR) and visual-cue function test (VCFT) responses were evaluated. Biomarkers, such as reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARSs), and catalase activity were determined in retinal tissue samples. DR significantly lowers the spatial frequency threshold (SFT) and time spent in the target quadrant (TSTQ), increases the reaching time in the visual-cue platform (RVCP), lowers retinal GSH and catalase activity levels, and elevates TBARS levels. The treatments of PBC and DEX also ameliorate STZ-induced DR alterations. The potential ameliorative activity of PBC in DR is attributed to its anti-diabetic, anti-oxidative, and control of blood-retinal barrier layer properties.},
}
@article {pmid37242429,
year = {2023},
author = {Lucenteforte, E and Finocchietti, M and Addis, A and Tettamanti, M and Varano, M and Parravano, M and Virgili, G},
title = {Polytherapy and Multimorbidity Pattern of Users of Anti-VEGF Drugs and Dexamethasone for the Treatment of Age-Related Macular Degeneration and other Vascular Retinopathies in Clinical Practice.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {5},
pages = {},
pmid = {37242429},
issn = {1424-8247},
abstract = {Introduction: Our aim was to describe the polytherapy and multimorbidity pattern of users of anti-VEGF and dexamethasone drugs for the treatment of these conditions, and to investigate their polytherapy and multimorbidity profiles, together with adherence and the burden of care. Methods: Descriptive, population-based, pharmacoepidemiology study on the users of anti-VEGF drugs, and secondarily intravitreal dexamethasone, for the treatment of age-related macular degeneration and other vascular retinopathies in clinical practice, using administrative databases of Lazio region, Italy. We used a cohort of 50,000 residents in Lazio in 2019 with same age as comparison. Polytherapy was assessed using databases of prescribed drugs intended for outpatient use. Multimorbidity was investigated with additional sources, such as hospital discharge records, outpatient care records, and disease-specific exemptions from co-payment. Each patient was followed for 1 to 3 years from the first intravitreal injection received. Results: 16,266 residents in Lazio who received the first IVI from 1 January 2011 to 31 December 2019, with at least 1 year of observation before index date, were included. The proportion of patients with at least one comorbidity was 54.0%. Patients used an average 8.6 (SD 5.3) concomitant drugs other than anti-VEGF used for injections. A large percentage of patients (39.0%) used 10 or more concomitant drugs, including antibacterials (62.9%), drugs for peptic ulcers (56.8%), anti-thrombotics (52.3%), NSAIDs (44.0%), and anti-dyslipidaemics (42.3%). The same proportions were found across patients of all ages, probably due to high prevalence of diabetes (34.3%), especially in younger age groups. When stratified by diabetes, a comparison of multimorbidity and polytherapy with a sample of 50,000 residents of the same age found that patients receiving IVIs used more drugs and had more comorbidities, particularly in non-diabetics. Lapses of care, whether short (absence of any type of contact for at least 60 days in the first year of follow-up and 90 in the second year) or long (90 days in the first and 180 days in the second year) were common: 66% and 51.7%, respectively. Conclusions: Patients receiving intravitreal drugs for retinal conditions have high multimorbidity and polytherapy rates. Their burden of care is aggravated by the large number of contacts with the eye care system for examinations and injections. Pursuing Minimally Disruptive Medicine to optimise patient care is a difficult goal for health systems, and more research on clinical pathways and their implementation is warranted.},
}
@article {pmid37241152,
year = {2023},
author = {Gałuszka, M and Pojda-Wilczek, D and Karska-Basta, I},
title = {Age-Related Macular or Retinal Degeneration?.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {5},
pages = {},
pmid = {37241152},
issn = {1648-9144},
mesh = {Humans ; *Retinal Degeneration ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Retina/diagnostic imaging ; },
abstract = {Age-related macular degeneration (AMD) is an eye disease that leads to progressive vision loss. Its prevalence has been increasing due to population aging. Previously, it was commonly believed that the disease affects the central retina, that is, the macula. However, recent studies have shown that it also involves the peripheral retina. Novel imaging techniques revealed various degenerative lesions that extend beyond the central macula. While their prevalence remains unknown, they seem to be more frequent in patients with late AMD. These findings suggest that the term "age-related retinal dysfunction" might be more adequate to describe some cases of AMD. They also raise the question about the role of electroretinography (ERG) as an objective measure of retinal function. The most common types of ERG tests used in AMD are multifocal (mfERG) and full-field ERG (ffERG). mfERG is more sensitive to macular changes, but the test is difficult to perform when fixation is unstable. On the other hand, ffERG reflects the function of the entire retina, not only the macular area. It helps assess the impact of peripheral retinal lesions and overall retinal function in patients with AMD. As ffERG results are normal in early-stage AMD, any abnormalities indicate that the disease is more severe and affects the entire retina. Anti-vascular endothelial growth factor injections improve retinal function in patients with neovascular AMD, as demonstrated by an increase in their ERG responses. More research is needed to assess the association between local and general retinal dysfunction. In this review, ffERG findings in patients with AMD are described and the usefulness of ffERG is discussed based on previous studies and cases from our own clinical practice.},
}
@article {pmid37240481,
year = {2023},
author = {Nepita, I and Raimondi, R and Piazza, S and Diaspro, A and Vidal-Aroca, F and Surdo, S and Romano, MR},
title = {Optical-Quality Assessment of a Miniaturized Intraocular Telescope.},
journal = {Journal of clinical medicine},
volume = {12},
number = {10},
pages = {},
pmid = {37240481},
issn = {2077-0383},
abstract = {Age-related macular degeneration (AMD) causes severe vision impairments, including blindness. An option to improve vision in AMD patients is through intraocular lenses and optics. Among others, implantable miniaturized telescopes, which direct light to healthy lateral regions of the retina, can be highly effective in improving vision in AMD patients. Yet, the quality of the restored vision might be sensitive to the optical transmission and aberrations of the telescope. To shed light on these points, we studied the in vitro optical performance of an implantable miniaturized telescope, namely, the SING IMT™ (Samsara Vision Ltd., Far Hills, NJ, USA) designed to improve vision in patients affected by late-stage AMD. Specifically, we measured the optical transmission in the spectral range 350-750 nm of the implantable telescope with a fiber-optic spectrometer. Wavefront aberrations were studied by measuring the wavefront of a laser beam after passing through the telescope and expanding the measured wavefront into a Zernike polynomial basis. Wavefront concavity indicated that the SING IMT™ behaves as a diverging lens with a focal length of -111 mm. The device exhibited even optical transmission in the whole visible spectrum and effective curvature suitable for retinal images magnification with negligible geometrical aberrations. Optical spectrometry and in vitro wavefront analysis provide evidence supporting the feasibility of miniaturized telescopes as high-quality optical elements and a favorable option for AMD visual impairment treatments.},
}
@article {pmid37240326,
year = {2023},
author = {Pinelli, R and Ferrucci, M and Berti, C and Biagioni, F and Scaffidi, E and Bumah, VV and Busceti, CL and Lenzi, P and Lazzeri, G and Fornai, F},
title = {The Essential Role of Light-Induced Autophagy in the Inner Choroid/Outer Retinal Neurovascular Unit in Baseline Conditions and Degeneration.},
journal = {International journal of molecular sciences},
volume = {24},
number = {10},
pages = {},
pmid = {37240326},
issn = {1422-0067},
support = {Ricerca Corrente 2023//Ministero della Salute/ ; },
mesh = {Humans ; *Endothelial Cells/metabolism ; Choroid/metabolism ; Retina/metabolism ; Bruch Membrane/metabolism ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/metabolism ; Autophagy ; },
abstract = {The present article discusses the role of light in altering autophagy, both within the outer retina (retinal pigment epithelium, RPE, and the outer segment of photoreceptors) and the inner choroid (Bruch's membrane, BM, endothelial cells and the pericytes of choriocapillaris, CC). Here autophagy is needed to maintain the high metabolic requirements and to provide the specific physiological activity sub-serving the process of vision. Activation or inhibition of autophagy within RPE strongly depends on light exposure and it is concomitant with activation or inhibition of the outer segment of the photoreceptors. This also recruits CC, which provides blood flow and metabolic substrates. Thus, the inner choroid and outer retina are mutually dependent and their activity is orchestrated by light exposure in order to cope with metabolic demand. This is tuned by the autophagy status, which works as a sort of pivot in the cross-talk within the inner choroid/outer retina neurovascular unit. In degenerative conditions, and mostly during age-related macular degeneration (AMD), autophagy dysfunction occurs in this area to induce cell loss and extracellular aggregates. Therefore, a detailed analysis of the autophagy status encompassing CC, RPE and interposed BM is key to understanding the fine anatomy and altered biochemistry which underlie the onset and progression of AMD.},
}
@article {pmid37240109,
year = {2023},
author = {Lenin, RR and Koh, YH and Zhang, Z and Yeo, YZ and Parikh, BH and Seah, I and Wong, W and Su, X},
title = {Dysfunctional Autophagy, Proteostasis, and Mitochondria as a Prelude to Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {24},
number = {10},
pages = {},
pmid = {37240109},
issn = {1422-0067},
support = {MOET32020-0001//Ministry of Education/ ; },
mesh = {Humans ; Aged ; *Retinal Pigment Epithelium/metabolism ; Proteostasis ; Autophagy/genetics ; Oxidative Stress/genetics ; *Macular Degeneration/pathology ; Mitochondria/metabolism ; },
abstract = {Retinal pigment epithelial (RPE) cell dysfunction is a key driving force of AMD. RPE cells form a metabolic interface between photoreceptors and choriocapillaris, performing essential functions for retinal homeostasis. Through their multiple functions, RPE cells are constantly exposed to oxidative stress, which leads to the accumulation of damaged proteins, lipids, nucleic acids, and cellular organelles, including mitochondria. As miniature chemical engines of the cell, self-replicating mitochondria are heavily implicated in the aging process through a variety of mechanisms. In the eye, mitochondrial dysfunction is strongly associated with several diseases, including age-related macular degeneration (AMD), which is a leading cause of irreversible vision loss in millions of people globally. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation, and increased numbers of mitochondrial DNA mutations. Mitochondrial bioenergetics and autophagy decline during aging because of insufficient free radical scavenger systems, the impairment of DNA repair mechanisms, and reductions in mitochondrial turnover. Recent research has uncovered a much more complex role of mitochondrial function and cytosolic protein translation and proteostasis in AMD pathogenesis. The coupling of autophagy and mitochondrial apoptosis modulates the proteostasis and aging processes. This review aims to summarise and provide a perspective on (i) the current evidence of autophagy, proteostasis, and mitochondrial dysfunction in dry AMD; (ii) current in vitro and in vivo disease models relevant to assessing mitochondrial dysfunction in AMD, and their utility in drug screening; and (iii) ongoing clinical trials targeting mitochondrial dysfunction for AMD therapeutics.},
}
@article {pmid37239053,
year = {2023},
author = {Damian, I and Muntean, GA and Galea-Holhoș, LB and Nicoară, SD},
title = {Advanced ImageJ Analysis in Degenerative Acquired Vitelliform Lesions Using Techniques Based on Optical Coherence Tomography.},
journal = {Biomedicines},
volume = {11},
number = {5},
pages = {},
pmid = {37239053},
issn = {2227-9059},
abstract = {Acquired vitelliform lesions (AVLs) are associated with a large spectrum of retinal diseases, among which is age-related macular degeneration (AMD). The purpose of this study was to characterize AVLs' evolution in AMD patients using optical coherence tomography (OCT) technology and ImageJ software. We measured AVLs' size and density and followed their impacts over surrounding retinal layers. Average retinal pigment epithelium (RPE) thickness in the central 1 mm quadrant (45.89 ± 27.84 µm vs. 15.57 ± 1.40 µm) was significantly increased, as opposed to the outer nuclear layer (ONL) thickness, which was decreased (77.94 ± 18.30 µm vs. 88.64 ± 7.65 µm) in the vitelliform group compared to the control group. We found a continuous external limiting membrane (ELM) in 55.5% of the eyes compared to a continuous ellipsoid zone (EZ) in 22.2% of the eyes in the vitelliform group. The difference between the mean AVLs' volume at baseline compared to the last visit for the nine eyes with ophthalmologic follow-up was not statistically significant (p = 0.725). The median follow-up duration was 11 months (range 5-56 months). Seven eyes (43.75%) were treated with intravitreal anti-vascular endothelium growth factor (anti-VEGF) agent injections, in which we noted a 6.43 ± 9 letter decrease in the best-corrected visual acuity (BCVA). The increased RPE thickness could suggest hyperplasia contrary to the decreased ONL, which could mirror the impact of the vitelliform lesion on photoreceptors (PR). Eyes that received anti-VEGF injections did not show signs of improvement regarding BCVA.},
}
@article {pmid37238939,
year = {2023},
author = {Begaj, T and Yuan, A and Lains, I and Li, A and Han, S and Susarla, G and Parikh, R and Sobrin, L},
title = {Presence of Choroidal Caverns in Patients with Posterior and Panuveitis.},
journal = {Biomedicines},
volume = {11},
number = {5},
pages = {},
pmid = {37238939},
issn = {2227-9059},
abstract = {Choroidal caverns (CCs) have been described in association with age-related macular degeneration and pachychoroid disease. However, it is unknown if caverns are found in patients with chronic non-infectious uveitis (NIU). Herein, we evaluated patients with NIU who had optical coherence tomography and indocyanine green angiography for CCs. Clinical and demographic characteristics were extracted from the chart review. Univariate and multivariate mixed-effects logistical models were used to assess the association between clinical and demographic factors and the presence of CCs. One hundred thirty-five patients (251 eyes) met the inclusion criteria: 1 eye had anterior uveitis, 5 had intermediate uveitis, 194 had posterior uveitis, and 51 had panuveitis. The prevalence of CCs was 10%. CCs were only observed in patients with posterior and panuveitis, with a prevalence of 10.8% and 7.8%, respectively. Multifocal choroiditis (MFC) was the type of uveitis where CCs were most frequently observed, with 40% of eyes with MFC having CCs. In addition, male sex (p = 0.024) was associated with CCs. There was no significant difference in the degree of intraocular inflammation or mean subfoveal choroidal thickness between CC+ and CC- eyes. This is the first study to describe CCs in uveitis. Overall, these findings suggest that caverns may be a sequela of structural and/or vascular perturbations in the choroid from uveitis.},
}
@article {pmid37238702,
year = {2023},
author = {Piri, N and Kaplan, HJ},
title = {Role of Complement in the Onset of Age-Related Macular Degeneration.},
journal = {Biomolecules},
volume = {13},
number = {5},
pages = {},
pmid = {37238702},
issn = {2218-273X},
mesh = {Humans ; Middle Aged ; *Quality of Life ; *Macular Degeneration/drug therapy ; Retina ; Complement System Proteins ; Risk Factors ; },
abstract = {Age-related macular degeneration (AMD) is a progressive degenerative disease of the central retina and the leading cause of severe loss of central vision in people over age 50. Patients gradually lose central visual acuity, compromising their ability to read, write, drive, and recognize faces, all of which greatly impact daily life activities. Quality of life is significantly affected in these patients, and there are worse levels of depression as a result. AMD is a complex, multifactorial disease in which age and genetics, as well as environmental factors, all play a role in its development and progression. The mechanism by which these risk factors interact and converge towards AMD are not fully understood, and therefore, drug discovery is challenging, with no successful therapeutic attempt to prevent the development of this disease. In this review, we describe the pathophysiology of AMD and review the role of complement, which is a major risk factor in the development of AMD.},
}
@article {pmid37238303,
year = {2023},
author = {Batıoğlu, F and Yanık, &#xd6; and Demirel, S and Özmert, E},
title = {Clinical Use of Optical Coherence Tomography Angiography in Retinal Diseases.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {10},
pages = {},
pmid = {37238303},
issn = {2075-4418},
abstract = {The advent of optical coherence tomography angiography (OCTA) is one of the cornerstones of fundus imaging. Essentially, its mechanism depends on the visualization of blood vessels by using the flow of erythrocytes as an intrinsic contrast agent. Although it has only recently come into clinical use, OCTA has become a non-invasive diagnostic tool for the diagnosis and follow-up of many retinal diseases, and the integration of OCTA in multimodal imaging has provided a better understanding of many retinal disorders. Here, we provide a detailed overview of the current applications of OCTA technology in the diagnosis and follow-up of various retinal disorders.},
}
@article {pmid37238165,
year = {2023},
author = {Zhao, J and Chandrasekaran, PR and Cheong, KX and Wong, M and Teo, K},
title = {New Concepts for the Diagnosis of Polypoidal Choroidal Vasculopathy.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {10},
pages = {},
pmid = {37238165},
issn = {2075-4418},
abstract = {Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (nAMD) that is characterized by a branching neovascular network and polypoidal lesions. It is important to differentiate PCV from typical nAMD as there are differences in treatment response between subtypes. Indocyanine green angiography (ICGA) is the gold standard for diagnosing PCV; however, ICGA is an invasive detection method and impractical for extensive use for regular long-term monitoring. In addition, access to ICGA may be limited in some settings. The purpose of this review is to summarize the utilization of multimodal imaging modalities (color fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and fundus autofluorescence (FAF)) in differentiating PCV from typical nAMD and predicting disease activity and prognosis. In particular, OCT shows tremendous potential in diagnosing PCV. Characteristics such as subretinal pigment epithelium (RPE) ring-like lesion, en face OCT-complex RPE elevation, and sharp-peaked pigment epithelial detachment provide high sensitivity and specificity for differentiating PCV from nAMD. With the use of more practical, non-ICGA imaging modalities, the diagnosis of PCV can be more easily made and treatment tailored as necessary for optimal outcomes.},
}
@article {pmid37237549,
year = {2023},
author = {Tomczak, W and Winkler-Lach, W and Tomczyk-Socha, M and Misiuk-Hojło, M},
title = {Advancements in Ocular Regenerative Therapies.},
journal = {Biology},
volume = {12},
number = {5},
pages = {},
pmid = {37237549},
issn = {2079-7737},
abstract = {The use of stem cells (SCs) has emerged as a promising avenue in ophthalmology, offering potential therapeutic solutions for various vision impairments and degenerative eye diseases. SCs possess the unique ability to self-renew and differentiate into specialised cell types, making them valuable tools for repairing damaged tissues and restoring visual function. Stem cell-based therapies hold significant potential for addressing conditions such as age-related macular degeneration (AMD), retinitis pigmentosa (RP), corneal disorders, and optic nerve damage. Therefore, researchers have explored different sources of stem cells, including embryonic stem cells (ESC), induced pluripotent stem cells (iPSCs), and adult stem cells, for ocular tissue regeneration. Preclinical studies and early-phase clinical trials have demonstrated promising outcomes, with some patients experiencing improved vision following stem cell-based interventions. However, several challenges remain, including optimising the differentiation protocols, ensuring transplanted cells' safety and long-term viability, and developing effective delivery methods. The field of stem cell research in ophthalmology witnesses a constant influx of new reports and discoveries. To effectively navigate these tons of information, it becomes crucial to summarise and systematise these findings periodically. In light of recent discoveries, this paper demonstrates the potential applications of stem cells in ophthalmology, focusing on their use in various eye tissues, including the cornea, retina, conjunctiva, iris, trabecular meshwork, lens, ciliary body, sclera, and orbital fat.},
}
@article {pmid37237234,
year = {2023},
author = {Patel, SS and Lally, DR and Hsu, J and Wykoff, CC and Eichenbaum, D and Heier, JS and Jaffe, GJ and Westby, K and Desai, D and Zhu, L and Khanani, AM},
title = {Correction: Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial.},
journal = {Eye (London, England)},
volume = {37},
number = {17},
pages = {3705},
doi = {10.1038/s41433-023-02548-2},
pmid = {37237234},
issn = {1476-5454},
}
@article {pmid37236984,
year = {2023},
author = {Cabral, D and Fradinho, AC and Zhang, Y and Zhou, H and Ramtohul, P and Ramakrishnan, MS and Pereira, T and Wang, RK and Freund, KB},
title = {Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {8572},
pmid = {37236984},
issn = {2045-2322},
mesh = {Humans ; Fluorescein Angiography/methods ; *Macular Degeneration/pathology ; Neovascularization, Pathologic/pathology ; *Retinal Neovascularization/pathology ; Choroid/blood supply ; Tomography, Optical Coherence/methods ; Retrospective Studies ; *Wet Macular Degeneration/pathology ; Angiogenesis Inhibitors ; },
abstract = {During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [- 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [- 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.},
}
@article {pmid37231906,
year = {2023},
author = {Cedro, L and Hoffmann, L and Hatz, K},
title = {Geographic Atrophy in AMD: Prognostic Factors Based on Long-Term Follow-Up.},
journal = {Ophthalmic research},
volume = {66},
number = {1},
pages = {791-800},
pmid = {37231906},
issn = {1423-0259},
mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Follow-Up Studies ; Prognosis ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; Atrophy/drug therapy ; Fluorescein Angiography/methods ; Disease Progression ; },
abstract = {INTRODUCTION: The aim of this large-scale long-term retrospective study was to show the enlargement rate (ER) of geographic atrophy (GA) in age-related macular degeneration (AMD), defined as complete retinal pigment epithelium and outer retinal atrophy (cRORA), to find predictors of progression in a clinical routine setting and to compare GA evaluation methods.<br><br>METHODS: All patients available in our database with follow-up of at least 24 months and cRORA in at least one eye, regardless of neovascular AMD being present, were included. SD-OCT and fundus autofluorescence (FAF) evaluations were performed according to a standardized protocol. The cRORA area ER, the cRORA square root area ER, the FAF GA area, and the condition of the outer retina (inner-/outer-segment [IS/OS] line and external limiting membrane [ELM] disruption scores) were determined.<br><br>RESULTS: 204 eyes of 129 patients were included. Mean follow-up time was 4.2 &#xb1; 2.2 (range 2-10) years. 109 of 204 (53.4%) eyes were classified as MNV-associated GA in AMD (initially or during follow-up); 95 of 204 (46.6%) eyes were classified as pure GA in AMD. The primary lesion was unifocal in 146 (72%) eyes and multifocal in 58 (28%) eyes. A strong correlation was observed between the area of cRORA (SD-OCT) and the FAF GA area (r = 0.924; p < 0.001). Mean ER was 1.44 &#xb1; 1.2 mm2/year, mean square root ER 0.29 &#xb1; 0.19 mm/year. There was no significant difference in mean ER between eyes without (pure GA) and with intravitreal anti-VEGF injections (MNV-associated GA) (0.30 &#xb1; 0.19 mm/year vs. 0.28 &#xb1; 0.20 mm/year; p = 0.466). Eyes with multifocal atrophy pattern at baseline had a significantly higher mean ER compared to eyes with unifocal pattern (0.34 &#xb1; 0.19 mm/year vs. 0.27 &#xb1; 1.19 mm/year; p = 0.008). There were moderate significant correlations between ELM and IS/OS disruption scores and visual acuity at baseline, 5 and 7 years (all r values ca. -0.5; p < 0.001). In multivariate regression analysis, a multifocal cRORA pattern at baseline (p = 0.022) and a smaller baseline lesion size (p = 0.036) were associated with a higher mean ER.<br><br>CONCLUSION: SD-OCT-evaluated cRORA area might serve as a GA parameter comparable to traditional FAF measurement in clinical routine. The dispersion pattern and baseline lesion size might be predictors of ER, whereas anti-VEGF treatment seems not to be associated with ER.},
}
@article {pmid37231616,
year = {2024},
author = {Bygglin, H and Immonen, I and Luoma, A and Hautamäki, A},
title = {Exudative age-related macular degeneration lesion components predicting microperimetric retinal sensitivity during anti-vascular endothelial growth factor treatment.},
journal = {Acta ophthalmologica},
volume = {102},
number = {1},
pages = {107-115},
doi = {10.1111/aos.15707},
pmid = {37231616},
issn = {1755-3768},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Endothelial Growth Factors ; Retinal Pigment Epithelium/pathology ; Vascular Endothelial Growth Factor A ; Atrophy ; *Cysts ; Hemorrhage/drug therapy/pathology ; *Macular Degeneration/drug therapy ; Tomography, Optical Coherence ; Fluorescein Angiography ; *Wet Macular Degeneration/diagnosis/drug therapy/pathology ; Intravitreal Injections ; },
abstract = {PURPOSE: To analyse the effect of exudative age-related macular degeneration (eAMD) lesion components on retinal sensitivity during anti-vascular endothelial growth factor treatment.<br><br>METHODS: Visual acuity, fluorescein and indocyanine green (ICG) angiographies, autofluorescence images, microperimetries and optical coherence tomographies (OCTs) of 24 eyes of 24 patients were prospectively analysed in a 2-year study of pro-re-nata bevacizumab treatment for eAMD. Microperimetries were aligned with the OCTs, angiographies and autofluorescence images. Thicknesses of the neuroretina, pigment epithelial (RPE) elevation, neuroepithelial detachment (NED), subretinal tissue (SRT) and cystic intraretinal fluid were measured under each stimulus site, and areas of type 1 and type 2 macular neovascularizations (MNVs), ICG plaque, haemorrhage and RPE atrophy were identified. The effects and predictive values of lesion components on retinal sensitivity were analysed with multivariate mixed linear models for repeated measurements.<br><br>RESULTS: The overall microperimetric retinal sensitivity increased during the first year (from 10.1&#x2009;dB at baseline to 11.9&#x2009;dB at 1&#x2009;year; p&#x2009;=&#x2009;0.021, Wilcoxon signed ranks), but remained the same during the second year (11.5&#x2009;dB, p&#x2009;=&#x2009;0.301). The baseline lesion components most strongly predicting deteriorated sensitivity at 1&#x2009;year were RPE atrophy, the area of Type 2 MNV, intraretinal cysts, haemorrhage, Type 1 MNV and retinal thickening >350&#x2009;&#x3bc;m. NED and RPE elevation had only small effects. At 2&#x2009;years, the predictive values of the baseline lesion components remained quite unchanged.<br><br>CONCLUSION: The most powerful predictors of retinal sensitivity loss during 2&#x2009;years of treatment were RPE atrophy, areas of haemorrhage, the area of MNVs, intraretinal cysts and SRT. RPE elevation and NED had lesser effects.},
}
@article {pmid37231279,
year = {2023},
author = {Kang, D and Lee, YJ and Nam, KT and Choi, M and Yun, C},
title = {Hyperreflective foci distribution in eyes with dry age-related macular degeneration with subretinal drusenoid deposits.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {10},
pages = {2821-2828},
pmid = {37231279},
issn = {1435-702X},
support = {K2212011//Korea University Ansan Hospital Grant/ ; },
mesh = {Humans ; *Retinal Drusen/diagnosis/etiology ; Retrospective Studies ; Prospective Studies ; *Geographic Atrophy ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: To investigate the distribution of hyperreflective foci (HRF) in eyes with dry age-related macular degeneration (AMD).<br><br>METHODS: We retrospectively reviewed optical coherence tomography (OCT) images of 58 dry AMD eyes presenting HRF. The distribution of HRF according to the early treatment diabetic retinopathy study area was analyzed according to the presence of subretinal drusenoid deposits (SDDs).<br><br>RESULTS: We classified 32 eyes and 26 eyes into the dry AMD with SDD group (SDD group) and dry AMD without SDD group (non-SDD group), respectively. The non-SDD group had higher prevalence and density of HRF at the fovea (65.4% and 1.71&#x2009;&#xb1;&#x2009;1.48) than the SDD group (37.5% and 0.48&#x2009;&#xb1;&#x2009;0.63, P&#x2009;=&#x2009;0.035 and P&#x2009;<&#x2009;0.001, respectively). However, the prevalence and density of HRF in the outer circle area of the SDD group (81.3% and 0.11&#x2009;&#xb1;&#x2009;0.09) were greater than those of the non-SDD group (53.8% and 0.05&#x2009;&#xb1;&#x2009;0.06, p&#x2009;=&#x2009;0.025 and p&#x2009;=&#x2009;0.004, respectively). The SDD group showed higher prevalence and mean densities of HRF in the superior and temporal area than in the non-SDD group (all, p&#x2009;<&#x2009;0.05).<br><br>CONCLUSION: HRF distributions in dry AMD varied according to the presence of SDDs. This might support that the degenerative features may be different between dry AMD eyes with and without SDDs.},
}
@article {pmid37228694,
year = {2023},
author = {Edmonds, R and Steffen, V and Honigberg, LA and Chang, MC},
title = {Alternative Complement Pathway Inhibition by Lampalizumab: Analysis of Data From Chroma and Spectri Phase III Clinical Trials.},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100286},
pmid = {37228694},
issn = {2666-9145},
abstract = {PURPOSE: Lampalizumab, an antigen-binding fragment of a humanized monoclonal antibody directed against complement factor D (CFD), is designed to treat geographic atrophy (GA) secondary to age-related macular degeneration. Given the lack of clinical efficacy observed in patients with GA in the phase III Chroma/Spectri trials, we investigated the impact of lampalizumab on the complement system in vivo. We developed 6 novel assays to measure changes in complement pathway activities in aqueous humor samples collected from patients enrolled in these trials.<br><br>DESIGN: Chroma/Spectri were double-masked, sham-controlled, 96-week trials.<br><br>PARTICIPANTS: Aqueous humor samples from 97 patients with bilateral GA across all groups (i.e., intravitreous lampalizumab 10 mg every 6 weeks, every 4 weeks, or corresponding sham procedures) were tested.<br><br>METHODS: Novel antibody capture assays were developed on the Simoa platform for complement factor B (CFB), the Bb fragment of CFB, intact complement component 3 (C3), processed C3, intact complement component 4 (C4), and processed C4.<br><br>MAIN OUTCOME MEASURES: The ratio of processed vs. intact complement factors (i.e., complement activity) in aqueous humor were assessed.<br><br>RESULTS: Patients treated with either of the lampalizumab regimens demonstrated an increase in CFD level at week 24 compared with baseline, along with a corresponding median reduction in the Bb:CFB ratio of 41% to 43%. There were no strong correlations between lampalizumab concentrations in aqueous humor and change in CFD levels or Bb:CFB ratio over time. No change in downstream C3 processing was observed with lampalizumab treatment. Additionally, there was no change in C4 processing.<br><br>CONCLUSIONS: The collection of aqueous humor samples from patients in Chroma and Spectri trials provided key insights on the effects of lampalizumab, a novel complement inhibitor, on local ocular complement activation. Lampalizumab inhibited the alternative complement pathway in the eyes of patients with GA; however, this did not translate into a measurable reduction in either classical or total complement activity, based on absence of changes in C4 and C3 processing, respectively.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37227711,
year = {2023},
author = {Domalpally, A and Pan, Q and Chew, EY},
title = {Association of Metformin With the Development of Age-related Macular Degeneration in the Diabetes Prevention Program Outcomes Study-Reply.},
journal = {JAMA ophthalmology},
volume = {141},
number = {7},
pages = {697},
pmid = {37227711},
issn = {2168-6173},
support = {Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Metformin/therapeutic use ; Hypoglycemic Agents/therapeutic use ; *Diabetes Mellitus, Type 2/complications/prevention &amp; control ; *Macular Degeneration/prevention &amp; control ; },
}
@article {pmid37227707,
year = {2023},
author = {Asensio-Sánchez, VM},
title = {Association of Metformin With the Development of Age-Related Macular Degeneration in the Diabetes Prevention Program Outcomes Study.},
journal = {JAMA ophthalmology},
volume = {141},
number = {7},
pages = {696},
doi = {10.1001/jamaophthalmol.2023.1889},
pmid = {37227707},
issn = {2168-6173},
mesh = {Humans ; *Metformin/therapeutic use ; Hypoglycemic Agents/therapeutic use ; *Diabetes Mellitus, Type 2/complications/prevention &amp; control ; *Macular Degeneration/prevention &amp; control ; },
}
@article {pmid37227479,
year = {2024},
author = {Bulloch, G and Seth, I and Zhu, Z and Sukumar, S and McNab, A},
title = {Ocular manifestations of obstructive sleep apnea: a systematic review and meta-analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {262},
number = {1},
pages = {19-32},
pmid = {37227479},
issn = {1435-702X},
mesh = {Humans ; Eyelid Diseases ; Glaucoma/etiology ; Keratoconus ; Optic Neuropathy, Ischemic/etiology ; Retinal Vein Occlusion/etiology ; *Sleep Apnea, Obstructive/complications ; },
abstract = {BACKGROUND: The association of obstructive sleep apnea (OSA) with development of eye diseases is unclear. This current systematic review and meta-analysis attempts to summarize and analyze associations between OSA and ocular disorders in the literature.<br><br>METHODS: PubMed, EMBASE, Google Scholar, Web Of Science, and Scopus databases were searched from 1901 to July 2022 in accordance with the Preferred Reporting in Systematic Review &amp; Meta-Analysis (PRISMA). Our primary outcome assessed the association between OSA and the odds of developing floppy eyelid syndrome (FES), glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), retinal vein occlusion (RVO), keratoconus (KC), idiopathic intracranial hypertension (IIH), age-related macular degeneration (AMD), and central serous chorioretinopathy (CSR) through odds ratio calculated at the 95% confidence interval.<br><br>RESULTS: Forty-nine studies were included for systematic review and meta-analysis. The pooled OR estimate was highest for NAION [3.98 (95% CI 2.38, 6.66)], followed by FES [3.68 (95% CI 2.18, 6.20)], RVO [2.71(95% CI 1.83, 4.00)], CSR [2.28 (95% CI 0.65, 7.97)], KC [1.87 (95% CI 1.16, 2.99)], glaucoma [1.49 (95% CI 1.16, 1.91)], IIH [1.29 (95% CI 0.33, 5.01)], and AMD [0.92 [95% CI 0.24, 3.58] All observed associations were significant (p&#x2009;<&#x2009;0.001) aside from IIH and AMD.<br><br>CONCLUSION: OSA is significantly associated with NAION, FES, RVO, CSR, KC, and glaucoma. Clinicians should be informed of these associations so early recognition, diagnosis, and treatment of eye disorders can be addressed in at-risk groups, and early referral to ophthalmic services is made to prevent vision disturbances. Similarly, ophthalmologists seeing patients with any of these conditions should consider screening and referring patients for assessment of possible OSA.},
}
@article {pmid37225720,
year = {2023},
author = {Xing, Y and Liang, S and Zhang, L and Ni, H and Zhang, X and Wang, J and Yang, L and Song, S and Li, HH and Jia, C and Jin, F},
title = {Combination of Lactobacillus fermentum NS9 and aronia anthocyanidin extract alleviates sodium iodate-induced retina degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {8380},
pmid = {37225720},
issn = {2045-2322},
mesh = {Animals ; Rats ; Anthocyanins/pharmacology ; *Limosilactobacillus fermentum ; *Photinia ; *Retinal Degeneration/chemically induced/drug therapy/prevention &amp; control ; Retina ; *Geographic Atrophy ; Plant Extracts/pharmacology ; },
abstract = {It is important to explore the effective approaches to prevent dry age-related macular degeneration (AMD). In this study, significantly decreased full-field electroretinograms wave amplitudes and disordered retina structures were detected in rat retinas of sodium iodate induced dry AMD model. Six a- and b-wave amplitudes and the antioxidant activities were significantly increased, and the outer nuclear layer thickness was significantly improved in the rat retinas treated with the combination of Lactobacillus fermentum NS9 (LF) and aronia anthocyanidin extract (AAE) compared with the model. The effects were much better than the treatment with AAE alone. The proteomics analysis showed the expressions of α-, β- and γ-crystallins were increased by 3-8 folds in AAE treated alone and by 6-11 folds in AAE + LF treatment compared with the model, which was further confirmed by immuno-blotting analysis. Analysis of gut microbial composition indicated that higher abundance of the genus Parasutterella and species P. excrementihominis was found in the AAE + LF treatment compared with the other groups. The results indicated that the combined treatment of AAE + LF is a potential way to prevent the retina degeneration which is significantly better than the AAE treated alone.},
}
@article {pmid37224477,
year = {2024},
author = {Ganesh, D and Corradetti, G and Sadda, SR},
title = {MACULAR NEOVASCULARIZATION IN A CASE OF LATE-ONSET RETINAL DEGENERATION TREATED WITH AFLIBERCEPT.},
journal = {Retinal cases &amp; brief reports},
volume = {18},
number = {5},
pages = {633-636},
pmid = {37224477},
issn = {1937-1578},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Female ; Aged ; *Recombinant Fusion Proteins/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; *Intravitreal Injections ; Retinal Degeneration/diagnosis/drug therapy ; Tomography, Optical Coherence ; Retinal Neovascularization/drug therapy/diagnosis/etiology ; Fluorescein Angiography ; Visual Acuity ; Fundus Oculi ; },
abstract = {PURPOSE: To describe the outcomes from treatment of macular neovascularization in an eye affected by late-onset retinal degeneration.<br><br>METHODS: A 72-year-old female patient presented with a history of decreased vision since several years. The patient was previously diagnosed with age-related macular degeneration and treated with anti-vascular endothelial growth factors.<br><br>RESULTS: Clinical examination of the retina and ultra-widefield color fundus photographs showed extensive atrophy in both eyes. The left eye showed macular neovascularization on fluorescein angiography, subretinal fluid on optical coherence tomography, and correspondent hemorrhages on the color fundus photography. Aflibercept anti-vascular endothelial factor treatment was used to treat the macular neovascularization in the left eye.<br><br>CONCLUSION: We report a case of genetically confirmed late-onset retinal degeneration (heterozygous pathogenic mutation p.Ser163Arg in one C1QTN5 allele) with advanced degeneration of the retina complicated by macular neovascularization, which responded well to treatment with a single aflibercept injection.},
}
@article {pmid37223523,
year = {2023},
author = {Li, X and Ma, B and Zhang, W and Song, Z and Zhang, X and Liao, M and Li, X and Zhao, X and Du, M and Yu, J and He, S and Yan, H},
title = {The essential role of N6-methyladenosine RNA methylation in complex eye diseases.},
journal = {Genes &amp; diseases},
volume = {10},
number = {2},
pages = {505-520},
pmid = {37223523},
issn = {2352-3042},
abstract = {There are many complex eye diseases which are the leading causes of blindness, however, the pathogenesis of the complex eye diseases is not fully understood, especially the underlying molecular mechanisms of N6-methyladenosine (m6A) RNA methylation in the eye diseases have not been extensive clarified. Our review summarizes the latest advances in the studies of m6A modification in the pathogenesis of the complex eye diseases, including cornea disease, cataract, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, Graves' disease, uveal melanoma, retinoblastoma, and traumatic optic neuropathy. We further discuss the possibility of developing m6A modification signatures as biomarkers for the diagnosis of the eye diseases, as well as potential therapeutic approaches.},
}
@article {pmid37222160,
year = {2023},
author = {Ryu, W and Park, CW and Kim, J and Lee, H and Chung, H},
title = {The Bcl-2/Bcl-xL Inhibitor ABT-263 Attenuates Retinal Degeneration by Selectively Inducing Apoptosis in Senescent Retinal Pigment Epithelial Cells.},
journal = {Molecules and cells},
volume = {46},
number = {7},
pages = {420-429},
pmid = {37222160},
issn = {0219-1032},
mesh = {Animals ; Mice ; *Retinal Degeneration ; Senotherapeutics ; *Antineoplastic Agents/pharmacology ; *Macular Degeneration/metabolism ; Apoptosis ; Epithelial Cells/metabolism ; Retinal Pigments/pharmacology ; Cellular Senescence ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.},
}
@article {pmid37219509,
year = {2023},
author = {Josan, AS and Farrance, I and Taylor, LJ and Adeyoju, D and Buckley, TMW and Jolly, JK and MacLaren, RE},
title = {Microperimetry Reliability Assessed From Fixation Performance.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {5},
pages = {21},
pmid = {37219509},
issn = {2164-2591},
support = {NIHR202821/DH_/Department of Health/United Kingdom ; },
mesh = {Humans ; *Scotoma ; Reproducibility of Results ; Visual Field Tests ; *Retinal Diseases ; Fundus Oculi ; },
abstract = {PURPOSE: Microperimetry provides an accurate assessment of central retinal sensitivity due to its fundus-tracking capability, but it has limited reliability indicators. One method currently employed, fixation loss, samples the optic nerve blind spot for positive responses; however, it is unclear if these responses arise from unintentional button presses or from tracking failure leading to stimuli misplacement. We investigated the relationship between blind spot scotoma positive responses (termed scotoma responses) and fixation.<br><br>METHODS: Part 1 of the study involved a custom grid of 181 points centered on the optic nerve that was constructed to map physiological blind spots in primary and simulated eccentric fixation positions. Scotoma responses and the 63% and 95% fixation bivariate contour ellipse areas (BCEA63 and BCEA95) were analyzed. In Part 2, fixation data from controls and patients with retinal diseases (234 eyes from 118 patients) were collected.<br><br>RESULTS: Part 1, a linear mixed model of 32 control participants, demonstrated significant (P < 0.001) correlation between scotoma responses and BCEA95. In Part 2, the upper 95% confidence intervals for BCEA95 were 3.7 deg2 for controls, 27.6 deg2 for choroideremia, 23.1 deg2 for typical rod-cone dystrophies, 21.4 deg2 for Stargardt disease, and 111.3 deg2 for age-related macular degeneration. Incorporating all pathology groups into an overall statistic resulted in an upper limit BCEA95 = 29.6 deg2.<br><br>CONCLUSIONS: Microperimetry reliability is significantly correlated to fixation performance, and BCEA95 provides a surrogate marker for test accuracy. Examinations of healthy individuals and patients with retinal disease are deemed unreliable if BCEA95 > 4 deg2 and BCEA95 > 30 deg2, respectively.<br><br>TRANSLATIONAL RELEVANCE: Microperimetry reliability should be assessed using fixation performance as summarized by BCEA95 rather than the level of fixation losses.},
}
@article {pmid37217935,
year = {2023},
author = {Zhu, X and Liu, W and Tang, X and Chen, Y and Ge, X and Ke, Q and Liang, X and Gan, Y and Zheng, Y and Zou, M and Deng, M and Liu, Y and Li, DW and Gong, L},
title = {The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
pages = {119},
pmid = {37217935},
issn = {1742-2094},
support = {81970787//National Natural Science Foundation of China/ ; 82271071//National Natural Science Foundation of China/ ; 82070969//National Natural Science Foundation of China/ ; SL2023A03J00488//Guangzhou Municipal University Joint Funding Project/ ; },
mesh = {Mice ; Animals ; *Retinal Degeneration/etiology/prevention &amp; control/metabolism ; Inflammation/metabolism ; Nucleotidyltransferases ; RNA ; },
abstract = {BACKGROUND: Chronic inflammation significantly contributes to photoreceptor death in blinding retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that act as key proinflammatory factors. We recently found the first-generation BET inhibitor JQ1 alleviated sodium iodate-induced retinal degeneration by suppressing cGAS-STING innate immunity. Here, we investigated the effects and mechanism of dBET6, a proteolysis‑targeting chimera (PROTAC) small molecule that selectively degrades BET by the ubiquitin‒proteasome system, in light-induced retinal degeneration.<br><br>METHODS: Mice were exposed to bright light to induce retinal degeneration, and the activation of cGAS-STING was determined by RNA-sequencing and molecular biology. Retinal function, morphology, photoreceptor viability and retinal inflammation were examined in the presence and absence of dBET6 treatment.<br><br>RESULTS: Intraperitoneal injection of dBET6 led to the rapid degradation of BET protein in the retina without detectable toxicity. dBET6 improved retinal responsiveness and visual acuity after light damage (LD). dBET6 also repressed LD-induced retinal macrophages/microglia activation, M&#xfc;ller cell gliosis, photoreceptor death and retinal degeneration. Analysis of single-cell RNA-sequencing results revealed cGAS-STING components were expressed in retinal microglia. LD led to dramatic activation of the cGAS-STING pathway, whereas dBET6 suppressed LD-induced STING expression in reactive macrophages/microglia and the related inflammatory response.<br><br>CONCLUSIONS: This study indicates targeted degradation of BET by dBET6 exerts neuroprotective effects by inhibiting cGAS-STING in reactive retinal macrophages/microglia, and is expected to become a new strategy for treatment of retinal degeneration.},
}
@article {pmid37217770,
year = {2023},
author = {Wei, W and Southern, J and Zhu, K and Li, Y and Cordeiro, MF and Veselkov, K},
title = {Deep learning to detect macular atrophy in wet age-related macular degeneration using optical coherence tomography.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {8296},
pmid = {37217770},
issn = {2045-2322},
mesh = {Humans ; *Deep Learning ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnostic imaging ; Neural Networks, Computer ; Atrophy ; },
abstract = {Here, we have developed a deep learning method to fully automatically detect and quantify six main clinically relevant atrophic features associated with macular atrophy (MA) using optical coherence tomography (OCT) analysis of patients with wet age-related macular degeneration (AMD). The development of MA in patients with AMD results in irreversible blindness, and there is currently no effective method of early diagnosis of this condition, despite the recent development of unique treatments. Using OCT dataset of a total of 2211 B-scans from 45 volumetric scans of 8 patients, a convolutional neural network using one-against-all strategy was trained to present all six atrophic features followed by a validation to evaluate the performance of the models. The model predictive performance has achieved a mean dice similarity coefficient score of 0.706 ± 0.039, a mean Precision score of 0.834 ± 0.048, and a mean Sensitivity score of 0.615 ± 0.051. These results show the unique potential of using artificially intelligence-aided methods for early detection and identification of the progression of MA in wet AMD, which can further support and assist clinical decisions.},
}
@article {pmid37215026,
year = {2024},
author = {Chowdhury, JM and Ruiz, EAC and Ohr, MP and Swindle-Reilly, KE and Ford Versypt, AN},
title = {Computer Modeling of Bevacizumab Drug Distribution After Intravitreal Injection in Rabbit and Human Eyes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.05.05.539491},
pmid = {37215026},
issn = {2692-8205},
support = {R01 EB032870/EB/NIBIB NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a progressive eye disease that causes loss of central vision and has no cure. Wet AMD is the late neovascular form treated with vascular endothelial growth factor (VEGF) inhibitors. VEGF is the critical driver of wet AMD. One common off-label anti-VEGF drug used in AMD treatment is bevacizumab. Experimental efforts have been made to investigate the pharmacokinetic (PK) behavior of bevacizumab in vitreous and aqueous humor. Still, the quantitative effect of elimination routes and drug concentration in the macula are not well understood. In this work, we developed two spatial models representing rabbit and human vitreous to better understand the PK behavior of bevacizumab. This study explores different cases of drug elimination and the effects of injection location on drug concentration profiles. The models are validated by comparing them with experimental data. Our results suggest that anterior elimination is dominant for bevacizumab clearance from rabbit vitreous, whereas both anterior and posterior elimination have similar importance in drug clearance from the human vitreous. Furthermore, results indicate that drug injections closer to the posterior segment of the vitreous help maintain relevant drug concentrations for longer, improving bevacizumab duration of action in the vitreous. The rabbit and human models predict bevacizumab concentration in the vitreous and fovea, enhancing knowledge and understanding of wet AMD treatment.},
}
@article {pmid37212795,
year = {2023},
author = {Elsner, AE},
title = {2022 Prentice Award Lecture: Advancing Retinal Imaging and Visual Function in Patient Management and Disease Mechanisms.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {100},
number = {6},
pages = {354-375},
pmid = {37212795},
issn = {1538-9235},
support = {UL1 RR025761/RR/NCRR NIH HHS/United States ; R01 EY004395/EY/NEI NIH HHS/United States ; R44 EY030829/EY/NEI NIH HHS/United States ; R41 EY030829/EY/NEI NIH HHS/United States ; R01 EY024315/EY/NEI NIH HHS/United States ; R44 EY018772/EY/NEI NIH HHS/United States ; R01 EY014106/EY/NEI NIH HHS/United States ; R41 EY026105/EY/NEI NIH HHS/United States ; R01 EY014375/EY/NEI NIH HHS/United States ; P30 EY003790/EY/NEI NIH HHS/United States ; R44 EY024186/EY/NEI NIH HHS/United States ; R44 EY020017/EY/NEI NIH HHS/United States ; P30 EY019008/EY/NEI NIH HHS/United States ; R01 EY007624/EY/NEI NIH HHS/United States ; R43 EY018772/EY/NEI NIH HHS/United States ; R41 EY028499/EY/NEI NIH HHS/United States ; R56 EB002346/EB/NIBIB NIH HHS/United States ; R01 EB002346/EB/NIBIB NIH HHS/United States ; },
mesh = {Animals ; Humans ; Retina ; *Macular Degeneration ; *Retinal Diseases/diagnostic imaging/pathology ; *Macular Edema/pathology ; *Awards and Prizes ; Tomography, Optical Coherence ; },
abstract = {Patient-based research plays a key role in probing basic visual mechanisms. Less-well recognized is the role of patient-based retinal imaging and visual function studies in elucidating disease mechanisms, which are accelerated by advances in imaging and function techniques and are most powerful when combined with the results from histology and animal models.A patient's visual complaints can be one key to patient management, but human data are also key to understanding disease mechanisms. Unfortunately, pathological changes can be difficult to detect. Before advanced retinal imaging, the measurement of visual function indicated the presence of pathological changes that were undetectable with existing clinical examination. Over the past few decades, advances in retinal imaging have increasingly revealed the unseen. This has led to great strides in the management of many diseases, particularly diabetic retinopathy and macular edema, and age-related macular degeneration. It is likely widely accepted that patient-based research, as in clinical trials, led to such positive outcomes. Both visual function measures and advanced retinal imaging have clearly demonstrated differences among retinal diseases. Contrary to initial thinking, sight-threatening damage in diabetes occurs to the outer retina and not only to the inner retina. This has been clearly indicated in patient results but has only gradually entered the clinical classifications and understanding of disease etiology. There is strikingly different pathophysiology for age-related macular degeneration compared with photoreceptor and retinal pigment epithelial genetic defects, yet research models and even some treatments confuse these. It is important to recognize the role that patient-based research plays in probing basic visual mechanisms and elucidating disease mechanisms, combining these findings with the concepts from histology and animal models. Thus, this article combines sample instrumentation from my laboratory and progress in the fields of retinal imaging and visual function.},
}
@article {pmid37211635,
year = {2023},
author = {Shaheen, AR and Uhr, JH and Sridhar, J and Yannuzzi, NA},
title = {Limitations of direct-to-consumer genetic testing for age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {33},
number = {6},
pages = {2059-2061},
doi = {10.1177/11206721231178054},
pmid = {37211635},
issn = {1724-6016},
abstract = {The availability of direct-to-consumer genetic testing (DTCGT) for age-related macular degeneration (AMD) provides the public with access to disease risk estimations that may be used to guide lifestyle adjustments. However, AMD development risk is more complex than can be captured by gene mutations alone. The methodologies employed by current DTCGTs to estimate AMD risk vary and are limited in several ways. Genotyping-based DTCGT is biased toward European ancestry and only considers a limited number of genes. Whole genome sequencing based DTCGTs uncovers several genetic variations with unknown relevance, making risk interpretation challenging. In this perspective, we describe the limitations of the DTCGT for AMD.},
}
@article {pmid37211091,
year = {2023},
author = {Tseng, VL and Kitayama, K and Yu, F and Pan, D and Coleman, AL},
title = {Social Vulnerability, Prevalence of Glaucoma, and Incidence of Glaucoma Surgery in the California Medicare Population.},
journal = {Ophthalmology. Glaucoma},
volume = {6},
number = {6},
pages = {616-625},
doi = {10.1016/j.ogla.2023.05.005},
pmid = {37211091},
issn = {2589-4196},
mesh = {Humans ; Aged ; United States/epidemiology ; *Glaucoma, Open-Angle/surgery ; Retrospective Studies ; Incidence ; Medicare ; Prevalence ; Cross-Sectional Studies ; Social Vulnerability ; *Glaucoma/epidemiology/surgery ; California/epidemiology ; },
abstract = {PURPOSE: To examine associations of Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index (SVI) scores with prevalence of glaucoma and incidence of glaucoma surgery in 2019 California Medicare beneficiaries.<br><br>DESIGN: Retrospective cross-sectional study.<br><br>PARTICIPANTS: 2019 California Medicare beneficiaries &#x2265; 65 years old with part A and part B coverage.<br><br>METHODS: The exposure of interest was SVI score, which was assessed overall and by themes. Outcomes included prevalence of glaucoma in the study population and incidence of glaucoma surgery in beneficiaries with glaucoma. Logistic regression modeling was performed to assess associations between quartiles of each type of SVI score, prevalence of glaucoma, and incidence of glaucoma surgery, controlling for age, sex, race/ethnicity, Charlson Comorbidity Index score, pseudophakia, and age-related macular degeneration.<br><br>MAIN OUTCOME MEASURES: Prevalence of any glaucoma, primary open angle glaucoma (POAG), secondary open angle glaucoma (SOAG), and angle closure glaucoma in all beneficiaries. Incidence of any glaucoma surgery, trabeculectomy, tube shunt, minimally invasive glaucoma surgery (MIGS), and cyclophotocoagulation (CPC) in beneficiaries with glaucoma.<br><br>RESULTS: Of 5&#x2009;725&#x2009;245 beneficiaries in the total study population, there were 215&#x2009;814 (3.8%) with any glaucoma, and of those with glaucoma, 10&#x2009;135/215&#x2009;814 (4.7%) underwent glaucoma surgery. In adjusted analyses for overall SVI score, where higher levels of SVI refer to higher levels of social vulnerability, there were decreased odds of any glaucoma (adjusted odds ratio [aOR]&#xa0;=&#xa0;0.83; 95% confidence interval [CI]&#xa0;=&#xa0;0.82, 0.84 for Q4 vs. Q1), POAG (aOR&#xa0;=&#xa0;0.85; 95% CI&#xa0;=&#xa0;0.84, 0.87 for Q4 vs. Q1), and SOAG (aOR&#xa0;=&#xa0;0.59; 95% CI&#xa0;=&#xa0;0.55, 0.63 for Q4 vs. Q1) in higher (Q4) vs. lower (Q1) SVI quartile. There were increased odds of any glaucoma surgery (aOR&#xa0;=&#xa0;1.19; 95% CI&#xa0;=&#xa0;1.12, 1.26 for Q4 vs. Q1), MIGS (aOR&#xa0;=&#xa0;1.24; 95% CI&#xa0;=&#xa0;1.15, 1.33 for Q4 vs. Q1), and CPC (aOR&#xa0;=&#xa0;1.49; 95% CI&#xa0;=&#xa0;1.29, 1.76 for Q4 vs. Q1) for higher (Q4) vs. lower (Q1) SVI quartile.<br><br>CONCLUSIONS: In the 2019 California Medicare population, there were variable associations between SVI score, prevalence of glaucoma, and incidence of glaucoma surgery. Further investigation is needed to understand the role of social, economic, and demographic factors in glaucoma care on the individual and structural levels.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37210384,
year = {2023},
author = {Jang, HY and Kim, SJ and Park, KS and Kim, JH},
title = {Klotho prevents transforming growth factor-β2-induced senescent-like morphological changes in the retinal pigment epithelium.},
journal = {Cell death &amp; disease},
volume = {14},
number = {5},
pages = {334},
pmid = {37210384},
issn = {2041-4889},
mesh = {Animals ; Mice ; Epithelial-Mesenchymal Transition ; *MicroRNAs/metabolism ; *Retinal Pigment Epithelium/metabolism ; Signal Transduction ; Transforming Growth Factor beta2/metabolism ; *Klotho Proteins/metabolism ; },
abstract = {Degenerative changes of the retinal pigment epithelium (RPE) triggered by transforming growth factor-β2 (TGF-β2) and oxidative stress play a critical role in the progression of age-related macular degeneration (AMD). The expression of α-klotho, an antiaging protein, declines with age, increasing the risk factors for age-related diseases. Here, we investigated the protective effects of soluble α-klotho on TGF-β2-induced RPE degeneration. The morphological changes induced by TGF-β2, including epithelial-mesenchymal transition (EMT), were attenuated in the mouse RPE by the intravitreal injection (IVT) of α-klotho. In ARPE19 cells, EMT and morphological alterations by TGF-β2 were attenuated by co-incubation with α-klotho. TGF-β2 decreased miR-200a accompanied by zinc finger e-box binding homeobox1 (ZEB1) upregulation and EMT, all of which were prevented by α-klotho co-treatment. Inhibitor of miR-200a mimicked TGF-β2-induced morphological changes, which were recovered by ZEP1 silencing, but not by α-klotho, implying the upstream regulation of α-klotho on miR-200a-ZEP1-EMT axis. α-Klotho inhibited receptor binding of TGF-β2, Smad2/3 phosphorylation, extracellular signal-regulated protein kinase 1/2 (ERK1/2)-a mechanistic target of rapamycin (mTOR) activation and oxidative stress via NADPH oxidase 4 (NOX4) upregulation. Furthermore, α-klotho recovered the TGF-β2-induced mitochondrial activation and superoxide generation. Interestingly, TGF-β2 upregulated α-klotho expression in the RPE cells, and genetic suppression of endogenous α-klotho aggravated TGF-β2-induced oxidative stress and EMT. Lastly, α-klotho abrogated senescence-associated signaling molecules and phenotypes induced by long-term incubation with TGF-β2. Hence, our findings indicate that the antiaging α-klotho plays a protective role against EMT and degeneration of the RPE, demonstrating the therapeutic potential for age-related retinal diseases, including the dry type of AMD.},
}
@article {pmid37210045,
year = {2023},
author = {Borodic, G},
title = {Botulinum toxin type A in multimodal management of age-related macular degeneration and related diseases.},
journal = {Toxicon : official journal of the International Society on Toxinology},
volume = {236},
number = {},
pages = {107170},
doi = {10.1016/j.toxicon.2023.107170},
pmid = {37210045},
issn = {1879-3150},
mesh = {Humans ; Aged ; Angiogenesis Inhibitors/therapeutic use/toxicity ; Antibodies, Monoclonal, Humanized/therapeutic use ; *Botulinum Toxins, Type A/therapeutic use ; *Choroidal Neovascularization/chemically induced/drug therapy ; *Wet Macular Degeneration/drug therapy/chemically induced/complications ; Edema/chemically induced ; Retrospective Studies ; Treatment Outcome ; Follow-Up Studies ; },
abstract = {Age related macular degeneration (AMD) is the major cause of visual loss in the aging population in the Western world. In past decade, intra ocular injections of anti-vascular endothelial growth factor (anti-VEGF) pharmaceuticals have revolutionized therapy for exudative (edematous-wet) AMD and become standard practice for the near term. However repeated intra-ocular injections are required for years and long terms results have been limited. The pathogenesis of this condition is multifactorial involving genetic, ischemic, inflammatory factors leading to neovascularization, edema and retinal pigment epithelial scaring resulting in photoreceptor destruction. Based on coincidental observation in reduction in AMD related macular edema on ocular coherence tomography (OCT) in a BoNT A treated patient with facial movement disease, BoNT-A at conventional doses targeting the para orbital area was added to therapeutic regiment in a small number of patients with exudative macular degeneration or related diseases. Measurements of edema and choriocapillaris using Spectral Doman (OCT) and Ocular Coherence Angiography (OCT-A) and Snellen visual acuity were made over the evaluation period. 15 eyes in 14 patients averaged 361 μm central sub foveal edema (CSFT) pre injection and average of 266 μm (CSFT) post injection over an average of 21 months and 5.7 cycles using BoNT A alone at conventional doses (n = 86 post injection measurements, paired t-test p < 0.001 two tailed). Visions at baseline in patients with 20/40 or worse averaged 20/100- pre injection improved to an average of 20/40- in the post injection period (n = 49 measurements p < 0.002 paired t-test). The previous data was added to a group of 12 more severely afflicted patients receiving anti VEGF (aflibercept or bevacizumab) (total 27 patients). With this 27-patient group, patients were followed for an average of 20 months and receiving average of 6 cycles at conventional doses. Improvement in exudative edema and vision were noted with pre injection baseline CSFT average 399.5, post injection average 267, n = 303 post measurement, independent t-test P < 0.0001.). Snellen vision 20/128 baseline average improved to average of 20/60- during post injection period (n = 157 post injection measurements, p < 0.0001 paired t-test to baseline). No substantial adverse effects were noted. Cyclic effects were noted corresponding to duration of action of BoNT-A on a number of patients. The above data is preliminary and is skewed toward early leakage for all conditions. BoNT A may have a role in the treatment of aged related macular degeneration. Controlled studies are needed with careful staging and baseline stratifications for multi-modal management paradigms. The findings are discussed relative to known botulinum toxin type A pharmacology and AMD pathogenesis.},
}
@article {pmid37208407,
year = {2023},
author = {Morelle, O and Wintergerst, MWM and Finger, RP and Schultz, T},
title = {Accurate drusen segmentation in optical coherence tomography via order-constrained regression of retinal layer heights.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {8162},
pmid = {37208407},
issn = {2045-2322},
mesh = {Humans ; *Retinal Drusen/diagnostic imaging ; Tomography, Optical Coherence/methods ; Reproducibility of Results ; Retina/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; *Calcinosis ; },
abstract = {Drusen are an important biomarker for age-related macular degeneration (AMD). Their accurate segmentation based on optical coherence tomography (OCT) is therefore relevant to the detection, staging, and treatment of disease. Since manual OCT segmentation is resource-consuming and has low reproducibility, automatic techniques are required. In this work, we introduce a novel deep learning based architecture that directly predicts the position of layers in OCT and guarantees their correct order, achieving state-of-the-art results for retinal layer segmentation. In particular, the average absolute distance between our model's prediction and the ground truth layer segmentation in an AMD dataset is 0.63, 0.85, and 0.44 pixel for Bruch's membrane (BM), retinal pigment epithelium (RPE) and ellipsoid zone (EZ), respectively. Based on layer positions, we further quantify drusen load with excellent accuracy, achieving 0.994 and 0.988 Pearson correlation between drusen volumes estimated by our method and two human readers, and increasing the Dice score to 0.71 ± 0.16 (from 0.60 ± 0.23) and 0.62 ± 0.23 (from 0.53 ± 0.25), respectively, compared to a previous state-of-the-art method. Given its reproducible, accurate, and scalable results, our method can be used for the large-scale analysis of OCT data.},
}
@article {pmid37207638,
year = {2023},
author = {Braunger, BM and Gießl, A and Schlötzer-Schrehardt, U},
title = {The Blood-ocular Barriers and their Dysfunction: Anatomy, Physiology, Pathology.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {240},
number = {5},
pages = {650-661},
doi = {10.1055/a-2063-8957},
pmid = {37207638},
issn = {1439-3999},
mesh = {Humans ; *Endothelial Cells ; Retina ; Blood-Retinal Barrier/physiology ; *Diabetic Retinopathy ; Retinal Pigment Epithelium ; },
abstract = {Complex barriers comprise the blood-aqueous (BAB) and the blood-retinal barrier (BRB), and separate anterior and posterior eye chambers, vitreous body, and sensory retina from the circulation. They prevent pathogens and toxins from entering the eye, control movement of fluid, proteins, and metabolites, and contribute to the maintenance of the ocular immune status. Morphological correlates of blood-ocular barriers are tight junctions between neighboring endothelial and epithelial cells, which function as gatekeepers of the paracellular transport of molecules, thereby limiting their uncontrolled access to ocular chambers and tissues. The BAB is composed of tight junctions between endothelial cells of the iris vasculature, endothelial cells of Schlemm's canal inner wall, and cells of the nonpigmented ciliary epithelium. The BRB consists of tight junctions between endothelial cells of the retinal vessels (inner BRB) and epithelial cells of the retinal pigment epithelium (outer BRB). These junctional complexes respond rapidly to pathophysiological changes, thus enabling vascular leakage of blood-derived molecules and inflammatory cells into ocular tissues and chambers. Blood-ocular barrier function, which can be clinically measured by laser flare photometry or fluorophotometry, is compromised in traumatic, inflammatory, or infectious processes, but also frequently contributes to the pathophysiology of chronic diseases of the anterior eye segment and the retina, as exemplified by diabetic retinopathy and age-related macular degeneration.},
}
@article {pmid37206564,
year = {2023},
author = {Zhang, C and Wang, W and Du, C and Li, H and Zhou, K and Luan, Z and Chang, Y and Liu, S and Wei, Y},
title = {Autophagy in the pharmacological activities of celastrol (Review).},
journal = {Experimental and therapeutic medicine},
volume = {25},
number = {6},
pages = {268},
pmid = {37206564},
issn = {1792-1015},
abstract = {Celastrol, a natural compound extracted from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, possesses broad-spectrum pharmacological properties. Autophagy is an evolutionarily conserved catabolic process through which cytoplasmic cargo is delivered to the lysosomes for degradation. Autophagy dysregulation contributes to multiple pathological processes. Therefore, targeting autophagic activity is a promising therapy for various diseases, as well as a drug-development strategy. According to previous studies, autophagy is specifically targeted and may be altered in response to celastrol treatment, highlighting that autophagy modulation is an important mechanism underlying the therapeutic efficacy of celastrol for the treatment of various diseases. The present study summarizes the currently available information regarding the role of autophagy in the effect of celastrol to exert anti-tumor, anti-inflammatory, immunomodulatory, neuroprotective, anti-atherosclerosis, anti-pulmonary fibrosis and anti-macular degeneration activities. The diverse signaling pathways involved are also analyzed to provide insight into the mechanisms of action of celastrol and thereby pave the way for establishing celastrol as an efficacious autophagy modulator in clinical practice.},
}
@article {pmid37206180,
year = {2023},
author = {Deng, Y and Jie, CH and Wang, JW and Li, YY and Liu, ZQ},
title = {Visual function and biofeedback training of patients with central vision loss: a review.},
journal = {International journal of ophthalmology},
volume = {16},
number = {5},
pages = {824-831},
pmid = {37206180},
issn = {2222-3959},
abstract = {Older individuals with macular diseases, such as age-related macular degeneration, experience central vision loss (CVL) due to degeneration of their photoreceptors and retinal cells. Patients with CVL may experience various vision impairments, including of visual acuity, fixation stability, contrast sensitivity, and stereoacuity. After CVL, most patients develop a preferred retinal locus outside the affected macular region, which serves as a new visual reference. In this review, we provide an overview of the visual function and impairment in individuals with CVL. In addition, the important role of biofeedback training on the visual function and activity of individuals with CVL is also reviewed. Accordingly, the location and development of the preferred retinal loci are discussed. Finally, this review discusses how to conduct biofeedback training to treat individuals with CVL.},
}
@article {pmid37203787,
year = {2023},
author = {Wang, J and Zong, Y and He, Y and Shi, G and Jiang, C},
title = {Domain Adaptation-Based Automated Detection of Retinal Diseases from Optical Coherence Tomography Images.},
journal = {Current eye research},
volume = {48},
number = {9},
pages = {836-842},
doi = {10.1080/02713683.2023.2212878},
pmid = {37203787},
issn = {1460-2202},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnosis/pathology ; Retina/diagnostic imaging/pathology ; Algorithms ; Area Under Curve ; },
abstract = {PURPOSE: To verify the effectiveness of domain adaptation in generalizing a deep learning-based anomaly detection model to unseen optical coherence tomography (OCT) images.<br><br>METHODS: Two datasets (source and target, where labelled training data was only available for the source) captured by two different OCT facilities were collected to train the model. We defined the model containing a feature extractor and a classifier as Model One and trained it with only labeled source data. The proposed domain adaptation model was defined as Model Two, which has the same feature extractor and classifier as Model One but has an additional domain critic in the training phase. We trained the Model Two with both the source and target datasets; the feature extractor was trained to extract domain-invariant features while the domain critic learned to capture the domain discrepancy. Finally, a well-trained feature extractor was used to extract domain-invariant features and a classifier was used to detect images with retinal pathologies in the two domains.<br><br>RESULTS: The target data consisted of 3,058 OCT B-scans captured from 163 participants. Model One achieved an area under the curve (AUC) of 0.912 [95% confidence interval (CI), 0.895-0.962], while Model Two achieved an overall AUC of 0.989 [95% CI, 0.982-0.993] for detecting pathological retinas from healthy samples. Moreover, Model Two achieved an average retinopathies detection accuracy of 94.52%. Heat maps showed that the algorithm focused on the area with pathological changes during processing, similar to manual grading in daily clinical work.<br><br>CONCLUSIONS: The proposed domain adaptation model showed a strong ability in reducing the domain distance between different OCT datasets.},
}
@article {pmid37203542,
year = {2023},
author = {Yildirim, K and Al-Nawaiseh, S and Ehlers, S and Schießer, L and Storck, M and Brix, T and Eter, N and Varghese, J},
title = {U-Net-Based Segmentation of Current Imaging Biomarkers in OCT-Scans of Patients with Age Related Macular Degeneration.},
journal = {Studies in health technology and informatics},
volume = {302},
number = {},
pages = {947-951},
doi = {10.3233/SHTI230315},
pmid = {37203542},
issn = {1879-8365},
mesh = {Humans ; *Algorithms ; *Macular Degeneration/diagnostic imaging ; Neural Networks, Computer ; Tomography, Optical Coherence/methods ; Biomarkers ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. In this work, the non-invasive imaging technique spectral domain optical coherence tomography (SD-OCT) is used to acquire retinal images, which are then analyzed using deep learning techniques. The authors trained a convolutional neural network (CNN) using 1300 SD-OCT scans annotated by trained experts for the presence of different biomarkers associated with AMD. The CNN was able to accurately segment these biomarkers and the performance was further enhanced through transfer learning with weights from a separate classifier, trained on a large external public OCT dataset to distinguish between different types of AMD. Our model is able to accurately detect and segment AMD biomarkers in OCT scans, which suggests that it could be useful for prioritizing patients and reducing ophthalmologists' workloads.},
}
@article {pmid37201739,
year = {2023},
author = {Swinkels, D and Baes, M},
title = {The essential role of docosahexaenoic acid and its derivatives for retinal integrity.},
journal = {Pharmacology &amp; therapeutics},
volume = {247},
number = {},
pages = {108440},
doi = {10.1016/j.pharmthera.2023.108440},
pmid = {37201739},
issn = {1879-016X},
mesh = {Mice ; Animals ; *Docosahexaenoic Acids/pharmacology/therapeutic use/analysis ; Retina/metabolism ; *Fatty Acids, Omega-3 ; Fatty Acids, Unsaturated/metabolism ; Fatty Acids/metabolism ; },
abstract = {The fatty acid composition of photoreceptor outer segment (POS) phospholipids diverges from other membranes, being highly enriched in polyunsaturated fatty acids (PUFAs). The most abundant PUFA is docosahexaenoic acid (DHA, C22:6n-3), an omega-3 PUFA that amounts to over 50% of the POS phospholipid fatty acid side chains. Interestingly, DHA is the precursor of other bioactive lipids such as elongated PUFAs and oxygenated derivatives. In this review, we present the current view on metabolism, trafficking and function of DHA and very long chain polyunsaturated fatty acids (VLC-PUFAs) in the retina. New insights on pathological features generated from PUFA deficient mouse models with enzyme or transporter defects and corresponding patients are discussed. Not only the neural retina, but also abnormalities in the retinal pigment epithelium are considered. Furthermore, the potential involvement of PUFAs in more common retinal degeneration diseases such as diabetic retinopathy, retinitis pigmentosa and age-related macular degeneration are evaluated. Supplementation treatment strategies and their outcome are summarized.},
}
@article {pmid37201365,
year = {2023},
author = {Zhang, C and Zhang, Y and Hu, X and Zhao, Z and Chen, Z and Wang, X and Zhang, Z and Jin, H and Zhang, J},
title = {Luteolin inhibits subretinal fibrosis and epithelial-mesenchymal transition in laser-induced mouse model via suppression of Smad2/3 and YAP signaling.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {116},
number = {},
pages = {154865},
doi = {10.1016/j.phymed.2023.154865},
pmid = {37201365},
issn = {1618-095X},
mesh = {Humans ; Male ; Animals ; Mice ; *Epithelial-Mesenchymal Transition ; *Retinal Pigment Epithelium/pathology ; Luteolin/pharmacology ; Mice, Inbred C57BL ; Fibrosis ; Collagen/metabolism ; Collagen Type I/metabolism ; Lasers ; },
abstract = {BACKGROUND: Subretinal fibrosis (SF) accounts for vision loss in patients with neovascular age-related macular degeneration (nAMD) even treated with adequate intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs. Currently, there is no treatment available to prevent or treat SF caused by nAMD.<br><br>PURPOSE: This study aims to investigate the potential effects of luteolin on SF and epithelial-mesenchymal transition (EMT) as well as the underlying molecular pathways both in vivo and in vitro.<br><br>METHODS: Seven-week-old male C57BL/6J mice were employed to establish laser-induced choroidal neovascularization (CNV) and SF. One day after the laser induction, luteolin was administered intravitreally. SF and CNV were assessed with the immunolabeling of collagen type I (collagen I) and isolectin B4 (IB4), respectively. RPE65 and &#x3b1;-SMA colocalization in the lesions was used to evaluate the extent of EMT in retinal pigment epithelial (RPE) cells by using immunofluorescence. In vitro, luteolin was administered to TGF&#x3b2;1-treated primary human RPE (phRPE) cells. RT-qPCR, Western blot and immunofluorescence were employed to evaluate the change of EMT-related molecules, epithelial markers, and relevant signaling pathways. The functional changes associated with EMT were investigated using the scratch assay, Transwell migration assay, and collagen gel contraction assay. CCK-8 was used to determine the cell viability of phRPE cells.<br><br>RESULTS: On day 7 and 14 after laser induction in mice, intravitreal injection of luteolin dramatically decreased the immunolabeled sizes of both collagen I and IB4, as well as the amount of colocalized double immunostaining of &#x3b1;-SMA and RPE65 in laser-induced SF lesions. In vitro, TGF&#x3b2;1-treated phRPE cells demonstrated increased cell migration and contraction capacity, accompanied with considerable overexpression of fibronectin, &#x3b1;-SMA, N-cadherin and vimentin, as well as downregulation of E-cadherin and ZO-1. The above changes were largely inhibited by luteolin co-incubation. Mechanistically, luteolin could evidently decrease the phosphorylation of Smad2/3, whereas increase the phosphorylation of YAP in TGF&#x3b2;1-treated phRPE cells.<br><br>CONCLUSION: This study demonstrates that luteolin exhibits the anti-fibrotic effect in a laser-induced mouse model by inhibiting EMT of RPE cells via deactivating Smad2/3 and YAP signaling, which provides a potential natural compound for the prevention and treatment of SF and fibrosis-related diseases.},
}
@article {pmid37199411,
year = {2023},
author = {Abyadeh, M and Gupta, V and Paulo, JA and Sheriff, S and Shadfar, S and Fitzhenry, M and Amirkhani, A and Gupta, V and Salekdeh, GH and Haynes, PA and Graham, SL and Mirzaei, M},
title = {Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases.},
journal = {Aging and disease},
volume = {14},
number = {4},
pages = {1311-1330},
pmid = {37199411},
issn = {2152-5250},
support = {R01 GM132129/GM/NIGMS NIH HHS/United States ; },
abstract = {Alzheimer's disease (AD) is the most common form of dementia that remains incurable and has become a major medical, social, and economic challenge worldwide. AD is characterized by pathological hallmarks of senile plaques (SP) and neurofibrillary tangles (NFTs) that damage the brain up to twenty years before a clinical diagnosis is made. Interestingly these pathological features have also been observed in retinal neurodegenerative diseases including age related macular degeneration (ARMD), glaucoma and diabetic retinopathy (DR). An association of AD with these diseases has been suggested in epidemiological studies and several common pathological events and risk factors have been identified between these diseases. The E4 allele of Apolipoprotein E (APOE) is a well-established genetic risk factor for late onset AD. The ApoE ε4 allele is also associated with retinal neurodegenerative diseases however in contrast to AD, it is considered protective in AMD, likewise ApoE E2 allele, which is a protective factor for AD, has been implicated as a risk factor for AMD and glaucoma. This review summarizes the evidence on the effects of ApoE in retinal neurodegenerative diseases and discusses the overlapping molecular pathways in AD. The involvement of ApoE in regulating amyloid beta (Aβ) and tau pathology, inflammation, vascular integrity, glucose metabolism and vascular endothelial growth factor (VEGF) signaling is also discussed.},
}
@article {pmid37199278,
year = {2024},
author = {Oncel, D and Corradetti, G and He, Y and Ashrafkhorasani, M and Nittala, MG and Stambolian, D and Pericak-Vance, MA and Haines, JL and Sadda, SR},
title = {Assessment of intraretinal hyperreflective foci using multimodal imaging in eyes with age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {1},
pages = {e126-e132},
pmid = {37199278},
issn = {1755-3768},
support = {R01 EY023164/EY/NEI NIH HHS/United States ; R01 EY030614/EY/NEI NIH HHS/United States ; RO1EY023164/EY/NEI NIH HHS/United States ; R01EY030614/EY/NEI NIH HHS/United States ; R01EY030614/EY/NEI NIH HHS/United States ; RO1EY023164/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/diagnosis ; Tomography, Optical Coherence/methods ; Fundus Oculi ; *Hyperpigmentation ; Multimodal Imaging ; Fluorescein Angiography ; Retrospective Studies ; },
abstract = {PURPOSE: This study aimed to investigate the correspondence between intraretinal hyperreflective foci (IHRF) identified on optical coherence tomography (OCT) B-scans with hyperpigmentation on colour fundus photography (CFP) or hyperreflectivity on infrared reflectance (IR) images in eyes with age-related macular degeneration (AMD).<br><br>METHODS: Flash CFP, IR images and OCT B-scans obtained at the same visit were evaluated. Individual IHRF identified on OCT B-scans were assessed for the qualitative presence or absence of a hypotransmission tail into the choroid. The corresponding IR image obtained at the time of OCT acquisition was analysed for the presence or absence of hyperreflectivity in this region. The IR images were manually registered to the CFP image, and CFP images were inspected for the presence or absence of hyperpigmentation at the location of IHRF.<br><br>RESULTS: From 122 eyes, a total of 494 IHRF were evaluated. For the primary analysis of qualitative presence or absence of hyperpigmentation on CFP and hyperreflectivity on IR at the locations corresponding to IHRF on OCT, 301 (61.0%) of the IHRFs demonstrated evidence of hyperpigmentation on CFP, while only 115 (23.3%) showed evidence of hyperreflectivity on IR. The qualitative determination of the presence or absence of an abnormality on CFP or IR were significantly different (p&#x2009;<&#x2009;0.0001). 327 (66.2%) of the IHRF showed hypotransmission, and 80.4% of these IHRF showed hyperpigmentation on CFP, though only 23.9% (p&#x2009;<&#x2009;0.0001) demonstrated hyperreflectivity on IR.<br><br>CONCLUSIONS: Less than two-thirds of IHRF evident on OCT manifest as hyperpigmentation on colour photos, though IHRF with posterior shadowing are more likely to be evident as pigment. IR imaging appears to be even more poorly sensitive for visualizing IHRF.},
}
@article {pmid37199035,
year = {2024},
author = {Leth-Møller Christensen, K and Kristjansen, DB and Vergmann, AS and Torp, TL and Peto, T and Grauslund, J},
title = {Retinal vascular structure independently predicts the initial treatment response in neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {102},
number = {1},
pages = {116-121},
doi = {10.1111/aos.15709},
pmid = {37199035},
issn = {1755-3768},
support = {//Velux Fonden/ ; },
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Prospective Studies ; Retina ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins/therapeutic use ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: Prediction of the early treatment response is important in neovascular age-related macular degeneration (nAMD). Hence, we aimed to test if non-invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment.<br><br>METHODS: In 58 eyes of 58 patients with treatment-na&#xef;ve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra- or subretinal fluid or macular haemorrhage.<br><br>RESULTS: Of 54 eyes attending follow-up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77&#x2009;years, p&#x2009;=&#x2009;0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24&#x2009;units, p&#x2009;=&#x2009;0.02) and venular length-diameter ratio (LDR) (7.3 vs. 15.9&#x2009;units, p&#x2009;=&#x2009;0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82-0.99, p&#x2009;=&#x2009;0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68-1.00, p&#x2009;=&#x2009;0.05, for each 0.01 unit increment).<br><br>CONCLUSION: Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long-term, prospective studies, this might help to guide treatment.},
}
@article {pmid37198519,
year = {2023},
author = {Menean, M and Sacconi, R and Vujosevic, S and Kesim, C and Quarta, A and Ribarich, N and Bottazzi, L and Hilely, A and Capuano, V and Souied, EH and Sarraf, D and Bandello, F and Querques, G},
title = {Subretinal Pseudocysts: A Comprehensive Analysis of this Novel OCT Finding.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {4},
pages = {2035-2048},
pmid = {37198519},
issn = {2193-8245},
abstract = {INTRODUCTION: In current clinical practice, several optical coherence tomography (OCT) biomarkers have been proposed for the assessment of severity and prognosis of different retinal diseases. Subretinal pseudocysts are subretinal cystoid spaces with hyperreflective borders and only a few single cases have been reported thus far. The aim of the study was to characterize and investigate this novel OCT finding, exploring its clinical outcome.<br><br>METHODS: Patients were evaluated retrospectively across different centers. The inclusion criterion was the presence of subretinal cystoid space on OCT scans, regardless of concurrent retinal diseases. Baseline examination was set as the first time the subretinal pseudocyst was identified by OCT. Medical and ophthalmological histories were collected at baseline. OCT and OCT-angiography were performed at baseline and at each follow-up examination.<br><br>RESULTS: Twenty-eight eyes were included in the study and 31 subretinal pseudocysts were characterized. Out of 28 eyes, 16 were diagnosed with neovascular age-related macular degeneration (AMD), 7 with central serous chorioretinopathy, 4 with diabetic retinopathy, and 1 with angioid streaks. Subretinal and intraretinal fluid were present in 25 and 13 eyes, respectively. Mean distance of the subretinal pseudocyst from the fovea was 686&#xa0;&#xb5;m. The diameter of the pseudocyst was positively associated with the height of the subretinal fluid (r&#x2009;=&#x2009;0.46; p&#x2009;=&#x2009;0.018) and central macular thickness (r&#x2009;=&#x2009;0.612; p&#x2009;=&#x2009;0.001). At follow-up, subretinal pseudocysts disappeared in most of the reimaged eyes (16 out of 17). Of these, two patients presented retinal atrophy at baseline examination and eight patients (47%) developed retinal atrophy at follow-up. Conversely, seven eyes (41%) did not develop retinal atrophy.<br><br>CONCLUSION: Subretinal pseudocysts are precarious OCT findings, usually disclosed in a context of subretinal fluid, and are probably transient alterations within the photoreceptor outer segments and retinal pigment epithelium (RPE) layer. Despite their nature, subretinal pseudocysts have been associated with photoreceptor loss and incomplete RPE definition.},
}
@article {pmid37197703,
year = {2023},
author = {Keenan, TDL},
title = {Geographic Atrophy in Age-Related Macular Degeneration: A Tale of Two Stages.},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100306},
pmid = {37197703},
issn = {2666-9145},
abstract = {PURPOSE: To examine disease progression in age-related macular degeneration (AMD) at 2 distinct stages, progression to geographic atrophy (GA) versus GA expansion, by comparison of the risk and protective factors at each stage.<br><br>DESIGN: Perspective.<br><br>SUBJECTS: Individuals at risk of GA or with GA.<br><br>MAIN OUTCOME MEASURES: Progression to GA and GA expansion rate.<br><br>METHODS: Critical synthesis of the literature on risk and protective factors, both environmental and genetic, for progression to GA versus GA expansion in AMD.<br><br>RESULTS: Comparison of the risk and protective factors demonstrates partially overlapping but partially distinct risk and protective factors for progression to GA versus GA expansion. Some factors are shared (i.e., operating in the same direction at both stages), others are not shared, and others seem to operate in different directions at each stage. Risk variants at ARMS2/HTRA1 increase both risk of progression to GA and GA expansion rate, presumably through the same mechanism. By contrast, risk and protective variants at CFH/CFHR alter risk of GA but not GA expansion rate. A risk variant at C3 increases risk of GA but is associated with slower GA expansion. In environmental factors, cigarette smoking is associated with increased risk of GA and faster GA expansion, whereas increased age is associated with the former but not the latter. The Mediterranean diet is associated with decreased progression at both stages, although the food components with the largest contributions seem to differ between the 2 stages. Some phenotypic features, such as reticular pseudodrusen and hyperreflective foci, are associated with increased progression at both stages.<br><br>CONCLUSIONS: Analysis of the risk and protective factors for progression to GA and GA expansion demonstrates partially overlapping but partially distinct elements at each stage: some are shared, some are relevant to 1 stage only, and some even seem active in opposite directions at each stage. Aside from ARMS2/HTRA1, the overlap between the genetic risk factors for the 2 stages is minimal. This suggests that the biologic mechanisms differ at least partially between the 2 disease stages. This has implications for therapeutic approaches and suggests that treatment aimed at the underlying disease processes may need to be tailored by stage.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37197577,
year = {2023},
author = {Callanan, D and Khurana, RN and Maturi, RK and Patel, S and Wykoff, CC and Eichenbaum, D and Khanani, AM and Hassan, T and Badger, H and Mehta, S and Le, G and Attar, M and Seal, J and Li, XY},
title = {Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration: MAPLE Study Results.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1367-1384},
pmid = {37197577},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the impact of modifying the abicipar pegol (abicipar) manufacturing process on the safety and treatment effect of abicipar in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A new process for manufacturing abicipar was developed to reduce host cell impurities. In a prospective, Phase 2, multicenter, open-label, 28-week clinical trial, patients (n=123) with active nAMD received intravitreal injections of abicipar 2 mg at baseline (day 1) and weeks 4, 8, 16, and 24. Outcome measures included proportion of patients with stable vision (<15-letter loss from baseline; primary endpoint), change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and adverse events.<br><br>RESULTS: Overall, 8.9% (11/123) of patients experienced intraocular inflammation (IOI) and discontinued treatment. IOI cases were assessed as mild (2.4% [3/123]), moderate (4.9% [6/123]), or severe (1.6% [2/123]) and resolved with steroid treatment. Visual acuity in most patients with IOI (8 of 11) recovered to baseline BCVA or better by study end. No cases of endophthalmitis or retinal vasculitis were reported. Stable vision was maintained for &#x2265;95.9% (&#x2265;118/123) of patients at all study visits. At week 28, treatment-na&#xef;ve patients showed a greater mean improvement from baseline in BCVA compared with previously treated patients (4.4 vs 1.8 letters) and a larger mean CRT reduction from baseline (98.5 vs 45.5 &#x3bc;m).<br><br>CONCLUSION: Abicipar produced using a modified manufacturing process showed a moderately lower incidence and severity of IOI compared with Phase 3 abicipar studies. Beneficial effects of treatment were demonstrated.},
}
@article {pmid37196903,
year = {2023},
author = {Yao, H and Xu, H and Wu, M and Lei, W and Li, L and Liu, D and Wang, Z and Ran, H and Ma, H and Zhou, X},
title = {Targeted long-term noninvasive treatment of choroidal neovascularization by biodegradable nanoparticles.},
journal = {Acta biomaterialia},
volume = {166},
number = {},
pages = {536-551},
doi = {10.1016/j.actbio.2023.05.021},
pmid = {37196903},
issn = {1878-7568},
mesh = {Rats ; Animals ; Endothelial Cells/metabolism ; *Choroidal Neovascularization/metabolism ; *Wet Macular Degeneration/drug therapy ; Inflammation ; *Nanoparticles/therapeutic use ; Disease Models, Animal ; },
abstract = {Choroidal neovascularization (CNV) is the main cause of vision loss in patients with wet age-related macular degeneration (AMD). Currently, treatment of these conditions requires repeated intravitreal injections, which may lead to complications such as infection and hemorrhage. So, we have developed a noninvasive method for treating CNV with nanoparticles, namely, Angiopoietin1-anti CD105-PLGA nanoparticles (AAP NPs), which targets the CNV to enhance drug accumulation at the site. These nanoparticles, with PLGA as a carrier, can slowly release encapsulated Angiopoietin 1 (Ang 1) and target the choroidal neovascularization marker CD105 to enhance drug accumulation, increases vascular endothelial cadherin (VE-cadherin) expression between vascular endothelial cells, effectively reduce neovascularization leakage and inhibit Angiopoietin 2(Ang 2) secretion by endothelial cells. In a rat model of laser-induced CNV, intravenous injection of AAP NPs exerted a good therapeutic effect in reducing CNV leakage and area. In short, these synthetic AAP NPs provide an effective alternative treatment for AMD and meet the urgent need for noninvasive treatment in neovascular ophthalmopathy. STATEMENT OF SIGNIFICANCE: This work describes the synthesis, injection-mediated delivery, in vitro and in vivo efficacy of targeted nanoparticles with encapsulated Ang1; via these nanoparticles, the drug can be targeted to choroidal neovascularization lesions for continuous treatment. The release of Ang1 can effectively reduce neovascularization leakage, maintain vascular stability, and inhibit Ang2 secretion and inflammation. This study provides a new approach for the treatment of wet age-related macular degeneration.},
}
@article {pmid37195657,
year = {2023},
author = {Xue, W and Peng, P and Wen, X and Meng, H and Qin, Y and Deng, T and Guo, S and Chen, T and Li, X and Liang, J and Zhang, F and Xie, Z and Jin, M and Liang, Q and Wei, L},
title = {Metagenomic Sequencing Analysis Identifies Cross-Cohort Gut Microbial Signatures Associated With Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {5},
pages = {11},
pmid = {37195657},
issn = {1552-5783},
mesh = {Humans ; Metagenome ; *Gastrointestinal Microbiome/genetics ; Dysbiosis/microbiology ; Bacteria/genetics/metabolism ; Bacteroidetes ; *Macular Degeneration/genetics ; },
abstract = {PURPOSE: Alterations in the gut microbiota have been associated with age-related macular degeneration (AMD). However, the dysbiosis shared by different ethnicity and geographic groups, which may associate with the disease pathogenesis, remain underexplored. Here, we characterized dysbiosis of the gut microbiota in patients with AMD from Chinese and Swiss cohorts and identified cross-cohort signatures associated with AMD.<br><br>METHODS: Shotgun metagenomic sequencing was performed on fecal samples from 30 patients with AMD and 30 healthy subjects. Published datasets with 138 samples from Swiss patients with AMD and healthy subjects were re-analyzed. Comprehensive taxonomic profiling was conducted by matching to the RefSeq genome database, metagenome-assembled genome (MAG) database, and Gut Virome Database (GVD). Functional profiling was performed by reconstruction of the MetaCyc pathways.<br><br>RESULTS: The &#x3b1;-diversity of the gut microbiota was decreased in patients with AMD according to taxonomic profiles generated using MAG but not RefSeq database as reference. The Firmicutes/Bacteroidetes ratio was also decreased in patients with AMD. Among AMD-associated bacteria shared between Chinese and Swiss cohorts, Ruminococcus callidus, Lactobacillus gasseri, and Prevotellaceae (f) uSGB 2135 were enriched in patients with AMD, whereas Bacteroidaceae (f) uSGB 1825 was depleted in patients with AMD and was negatively associated with hemorrhage size. Bacteroidaceae was one of the major hosts of phages associated with AMD. Three degradation pathways were reduced in AMD.<br><br>CONCLUSIONS: These results demonstrated that dysbiosis of the gut microbiota was associated with AMD. We identified cross-cohort gut microbial signatures involving bacteria, viruses, and metabolic pathways, which potentially serve as promising targets for the prevention or treatment of AMD.},
}
@article {pmid37195339,
year = {2023},
author = {Matsumoto, H and Hoshino, J and Nakamura, K and Nagashima, T and Akiyama, H},
title = {Short-term outcomes of intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {10},
pages = {2945-2952},
pmid = {37195339},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor ; Tomography, Optical Coherence ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors ; *Wet Macular Degeneration/diagnosis/drug therapy ; Treatment Outcome ; },
abstract = {PURPOSE: To investigate the efficacy and safety of loading phase treatment with 3 monthly intravitreal injections of faricimab for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: We retrospectively analyzed 16-week outcomes of 40 consecutive eyes of 38 patients with treatment-na&#xef;ve nAMD. Three monthly injections of faricimab were administered to all eyes as a loading phase treatment. Best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), and dry macula achievement were all assessed every 4&#xa0;weeks. Moreover, the regression of polypoidal lesions was evaluated after the loading phase.<br><br>RESULTS: BCVA was 0.33&#x2009;&#xb1;&#x2009;0.41 at baseline and showed significant improvement to 0.22&#x2009;&#xb1;&#x2009;0.36 at week 16 (P&#x2009;<&#x2009;0.01). Foveal thickness was 278&#x2009;&#xb1;&#x2009;116&#xa0;&#xb5;m at baseline, decreasing significantly to 173&#x2009;&#xb1;&#x2009;48&#xa0;&#xb5;m at week 16 (P&#x2009;<&#x2009;0.01). CCT was 214&#x2009;&#xb1;&#x2009;98&#xa0;&#xb5;m at baseline, decreasing significantly to 192&#x2009;&#xb1;&#x2009;89&#xa0;&#xb5;m at week 16 (P&#x2009;<&#x2009;0.01). Dry macula was achieved in 31 eyes (79.5%) at week 16. Indocyanine green angiography after the loading phase revealed complete regression of polypoidal lesions in 11 of 18 eyes (61.1%) with polypoidal lesions. One eye (2.5%) developed vitritis without visual loss at week 16.<br><br>CONCLUSION: Loading phase treatment with intravitreal faricimab appears to generally be safe and effective for improving visual acuity and reducing exudative changes in eyes with nAMD.},
}
@article {pmid37195035,
year = {2023},
author = {Defenderfer, MK and Demirayak, P and Fleming, LL and DeCarlo, DK and Stewart, P and Visscher, KM},
title = {Cortical plasticity in central vision loss: Cortical thickness and neurite structure.},
journal = {Human brain mapping},
volume = {44},
number = {10},
pages = {4120-4135},
pmid = {37195035},
issn = {1097-0193},
support = {UL1 TR000165/TR/NCATS NIH HHS/United States ; P30 AG022838/AG/NIA NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; U01 EY025858/EY/NEI NIH HHS/United States ; R01 EY031589/EY/NEI NIH HHS/United States ; F99 NS113424/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; Neurites/pathology ; *Visual Cortex/diagnostic imaging/pathology ; Visual Perception ; Visual Fields ; Retina/pathology ; *Macular Degeneration/pathology ; },
abstract = {Late-stage macular degeneration (MD) often causes retinal lesions depriving an individual of central vision, forcing them to learn to use peripheral vision for daily tasks. To compensate, many patients develop a preferred retinal locus (PRL), an area of peripheral vision used more often than equivalent regions of spared vision. Thus, associated portions of cortex experience increased use, while portions of cortex associated with the lesion are deprived of sensory input. Prior research has not well examined the degree to which structural plasticity depends on the amount of use across the visual field. Cortical thickness, neurite density, and orientation dispersion were measured at portions of cortex associated with the PRL, the retinal lesion, and a control region in participants with MD as well as age-matched, gender-matched, and education-matched controls. MD participants had significantly thinner cortex in both the cortical representation of the PRL (cPRL) and the control region, compared with controls, but no significant differences in thickness, neurite density, or orientation dispersion were found between the cPRL and the control region as functions of disease or onset. This decrease in thickness is driven by a subset of early-onset participants whose patterns of thickness, neurite density, and neurite orientation dispersion are distinct from matched control participants. These results suggest that people who develop MD earlier in adulthood may undergo more structural plasticity than those who develop it late in life.},
}
@article {pmid37194147,
year = {2023},
author = {Jiang, H and Xu, Z},
title = {Hyaluronic acid-based nanoparticles to deliver drugs to the ocular posterior segment.},
journal = {Drug delivery},
volume = {30},
number = {1},
pages = {2204206},
pmid = {37194147},
issn = {1521-0464},
mesh = {Humans ; *Hyaluronic Acid/chemistry ; Pharmaceutical Preparations/metabolism ; Retina/metabolism ; Drug Delivery Systems ; *Nanoparticles ; },
abstract = {Ocular posterior segment diseases such as uveitis, X-linked juvenile retinoschisis, or age-related macular degeneration usually result in progressive and irreversible vision loss. Although intravitreal injection is the main way to deliver drugs to the posterior eye, it still has shortcomings as an invasive operation. Nanocontrolled drug delivery technology is a promising option to avoid frequent injections. Due to the particularity of the human intraocular structure, drugs have unique pharmacokinetic characteristics in the eye. Various nanoparticles have been successfully investigated in experimental studies for vitreous injection, with advantages and drawbacks. Here, we introduce an ideal nanopolymer modifier to build nanodelivery systems in vitreous cavities. Hyaluronic acid (HA) is a natural polysaccharide with a broad molecular weight range, negatively charged surface, ligand-receptor binding capabilities, and hyaluronidase breakdown capability. Advances in CD44 receptor targeting for HA-based nanoparticles can improve mobility and penetration in the vitreous and retina, stabilize the nanoparticles, and regulate drug release. This review summarizes the intravitreal administration of nanoplatforms based on HA and the benefits of HA in drug delivery systems.},
}
@article {pmid37190063,
year = {2023},
author = {Sripathi, SR and Hu, MW and Turaga, RC and Mikeasky, R and Satyanarayana, G and Cheng, J and Duan, Y and Maruotti, J and Wahlin, KJ and Berlinicke, CA and Qian, J and Esumi, N and Zack, DJ},
title = {IKKβ Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium.},
journal = {Cells},
volume = {12},
number = {8},
pages = {},
pmid = {37190063},
issn = {2073-4409},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY031714/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; Epithelial-Mesenchymal Transition ; I-kappa B Kinase/metabolism ; Tumor Necrosis Factor-alpha/pharmacology/metabolism ; *Vitreoretinopathy, Proliferative/metabolism ; Transforming Growth Factor beta/pharmacology/metabolism ; Protein Serine-Threonine Kinases/metabolism ; Stem Cells/metabolism ; },
abstract = {Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF-β) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), can induce RPE-EMT; however, small molecule inhibitors of RPE-EMT have been less well studied. Here, we demonstrate that BAY651942, a small molecule inhibitor of nuclear factor kapa-B kinase subunit beta (IKKβ) that selectively targets NF-κB signaling, can modulate TGF-β/TNF-α-induced RPE-EMT. Next, we performed RNA-seq studies on BAY651942 treated hRPE monolayers to dissect altered biological pathways and signaling events. Further, we validated the effect of IKKβ inhibition on RPE-EMT-associated factors using a second IKKβ inhibitor, BMS345541, with RPE monolayers derived from an independent stem cell line. Our data highlights the fact that pharmacological inhibition of RPE-EMT restores RPE identity and may provide a promising approach for treating retinal diseases that involve RPE dedifferentiation and EMT.},
}
@article {pmid37189405,
year = {2023},
author = {Harmening, N and Johnen, S and Izsvák, Z and Ivics, Z and Kropp, M and Bascuas, T and Walter, P and Kreis, A and Pajic, B and Thumann, G},
title = {Enhanced Biosafety of the Sleeping Beauty Transposon System by Using mRNA as Source of Transposase to Efficiently and Stably Transfect Retinal Pigment Epithelial Cells.},
journal = {Biomolecules},
volume = {13},
number = {4},
pages = {},
pmid = {37189405},
issn = {2218-273X},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; *Containment of Biohazards ; Vascular Endothelial Growth Factors/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal neovascularization (CNV), which leads to retinal pigment epithelial (RPE) cell and photoreceptor degeneration and blindness if untreated. Since blood vessel growth is mediated by endothelial cell growth factors, including vascular endothelial growth factor (VEGF), treatment consists of repeated, often monthly, intravitreal injections of anti-angiogenic biopharmaceuticals. Frequent injections are costly and present logistic difficulties; therefore, our laboratories are developing a cell-based gene therapy based on autologous RPE cells transfected ex vivo with the pigment epithelium derived factor (PEDF), which is the most potent natural antagonist of VEGF. Gene delivery and long-term expression of the transgene are enabled by the use of the non-viral Sleeping Beauty (SB100X) transposon system that is introduced into the cells by electroporation. The transposase may have a cytotoxic effect and a low risk of remobilization of the transposon if supplied in the form of DNA. Here, we investigated the use of the SB100X transposase delivered as mRNA and showed that ARPE-19 cells as well as primary human RPE cells were successfully transfected with the Venus or the PEDF gene, followed by stable transgene expression. In human RPE cells, secretion of recombinant PEDF could be detected in cell culture up to one year. Non-viral ex vivo transfection using SB100X-mRNA in combination with electroporation increases the biosafety of our gene therapeutic approach to treat nvAMD while ensuring high transfection efficiency and long-term transgene expression in RPE cells.},
}
@article {pmid37187551,
year = {2023},
author = {Li, XQ and Zhu, KW and Lai, J and Wu, J and Guo, XF},
title = {Esophageal Ulcer After Intravitreal Ranibizumab Injection in a Patient With Age-Related Macular Degeneration.},
journal = {Gastroenterology research},
volume = {16},
number = {2},
pages = {118-124},
pmid = {37187551},
issn = {1918-2805},
abstract = {Ranibizumab is a monoclonal antibody fragment targeted against vascular endothelial growth factor (VEGF) A isoform (VEGF-A). This study aimed to report a case of esophageal ulcer that developed soon after intravitreal ranibizumab injection in a patient with age-related macular degeneration (AMD). A 53-year-old male patient diagnosed with AMD received ranibizumab through intravitreal injection in the left eye. Mild dysphagia occurred 3 days after receiving intravitreal ranibizumab injection for the second time. The dysphagia exacerbated remarkably and was accompanied by hemoptysis 1 day after receiving ranibizumab for the third time. Severe dysphagia accompanied by intense retrosternal pain and pant emerged after injecting ranibizumab for the fourth time. An esophageal ulcer was observed through ultrasound gastroscopy, covered with fibrinous tissue, and surrounded by flushing and congestive mucosae. The patient received proton pump inhibitor (PPI) therapy combined with traditional Chinese medicine (TCM) after discontinuation of ranibizumab. The dysphagia and retrosternal pain were gradually relieved after treatment. Afterwards, the esophageal ulcer has not relapsed since permanent discontinuation of ranibizumab. To our best knowledge, this was the first case of esophageal ulcer related to intravitreal ranibizumab injection. Our study indicated that VEGF-A played a potential role in the development of esophageal ulceration.},
}
@article {pmid37187367,
year = {2023},
author = {Maran, JJ and Adesina, MM and Green, CR and Kwakowsky, A and Mugisho, OO},
title = {The central role of the NLRP3 inflammasome pathway in the pathogenesis of age-related diseases in the eye and the brain.},
journal = {Ageing research reviews},
volume = {88},
number = {},
pages = {101954},
doi = {10.1016/j.arr.2023.101954},
pmid = {37187367},
issn = {1872-9649},
mesh = {Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Brain/metabolism ; *Parkinson Disease/metabolism ; *Alzheimer Disease/etiology/metabolism ; Inflammation/metabolism ; *Glaucoma/etiology/metabolism ; Aging ; },
abstract = {With increasing age, structural changes occur in the eye and brain. Neuronal death, inflammation, vascular disruption, and microglial activation are among many of the pathological changes that can occur during ageing. Furthermore, ageing individuals are at increased risk of developing neurodegenerative diseases in these organs, including Alzheimer's disease (AD), Parkinson's disease (PD), glaucoma and age-related macular degeneration (AMD). Although these diseases pose a significant global public health burden, current treatment options focus on slowing disease progression and symptomatic control rather than targeting underlying causes. Interestingly, recent investigations have proposed an analogous aetiology between age-related diseases in the eye and brain, where a process of chronic low-grade inflammation is implicated. Studies have suggested that patients with AD or PD are also associated with an increased risk of AMD, glaucoma, and cataracts. Moreover, pathognomonic amyloid-β and α-synuclein aggregates, which accumulate in AD and PD, respectively, can be found in ocular parenchyma. In terms of a common molecular pathway that underpins these diseases, the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome is thought to play a vital role in the manifestation of all these diseases. This review summarises the current evidence regarding cellular and molecular changes in the brain and eye with age, similarities between ocular and cerebral age-related diseases, and the role of the NLRP3 inflammasome as a critical mediator of disease propagation in the eye and the brain during ageing.},
}
@article {pmid37186528,
year = {2023},
author = {Farzad, S and Kosta, P and Iseri, E and Walston, ST and Bouteiller, JC and Pfeiffer, RL and Sigulinsky, CL and Yang, JH and Garcia, JC and Anderson, JR and Jones, BW and Lazzi, G},
title = {Impact of Retinal Degeneration on Response of ON and OFF Cone Bipolar Cells to Electrical Stimulation.},
journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society},
volume = {31},
number = {},
pages = {2424-2437},
pmid = {37186528},
issn = {1558-0210},
support = {R21 EY028744/EY/NEI NIH HHS/United States ; R01 EY015128/EY/NEI NIH HHS/United States ; R01 EY028927/EY/NEI NIH HHS/United States ; T32 EY024234/EY/NEI NIH HHS/United States ; U01 EB025830/EB/NIBIB NIH HHS/United States ; P30 EY014800/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Rabbits ; *Retinal Degeneration/therapy ; Retina/physiology ; *Retinitis Pigmentosa/therapy ; Axons/physiology ; Electric Stimulation/methods ; },
abstract = {In retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the photoreceptors become stressed and start to degenerate in the early stages of the disease. Retinal prosthetic devices have been developed to restore vision in patients by applying electrical stimulation to the surviving retinal cells. However, these devices provide limited visual perception as the therapeutic interventions are generally considered in the later stages of the disease when only inner retinal layer cells are left. A potential treatment option for retinal degenerative diseases in the early stages can be stimulating bipolar cells, which receive presynaptic signals from photoreceptors. In this work, we constructed computational models of healthy and degenerated (both ON and OFF-type) cone bipolar cells (CBCs) with realistic morphologies extracted from connectomes of the healthy and early-stage degenerated rabbit retina. We examined these cells' membrane potential and axon terminal calcium current differences when subjected to electrical stimulation. In addition, we investigated how differently healthy and degenerated cells behave with respect to various stimulation parameters, including pulse duration and cells' distance from the stimulating electrode. The results suggested that regardless of the position of the OFF CBCs in the retina model, there is not a significant difference between the membrane potential of healthy and degenerate cells when electrically stimulated. However, the healthy ON CBC axon terminal membrane potential rising time-constant is shorter (0.29 ± 0.03 ms) than the degenerated cells (0.8 ± 0.07 ms). Moreover, the ionic calcium channels at the axon terminals of the cells have a higher concentration and higher current in degenerated cells (32.24 ± 6.12 pA) than the healthy cells (13.64 ± 2.88 pA) independently of the cell's position.},
}
@article {pmid37181750,
year = {2023},
author = {Chatterjee, A and Singh, R},
title = {Extracellular vesicles: an emerging player in retinal homeostasis.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1059141},
pmid = {37181750},
issn = {2296-634X},
support = {R01 EY028167/EY/NEI NIH HHS/United States ; R01 EY030183/EY/NEI NIH HHS/United States ; R01 EY033192/EY/NEI NIH HHS/United States ; R21 EY030817/EY/NEI NIH HHS/United States ; },
abstract = {Extracellular vesicles (EVs) encompass secreted membrane vesicles of varied sizes, including exosomes (-30-200 nm) and microvesicles (MVs) that are ∼100-1,000 nm in size. EVs play an important role in autocrine, paracrine, and endocrine signaling and are implicated in myriad human disorders including prominent retinal degenerative diseases, like age related macular degeneration (AMD) and diabetic retinopathy (DR). Studies of EVs in vitro using transformed cell lines, primary cultures, and more recently, induced pluripotent stem cell derived retinal cell type(s) (e.g., retinal pigment epithelium) have provided insights into the composition and function of EVs in the retina. Furthermore, consistent with a causal role of EVs in retinal degenerative diseases, altering EV composition has promoted pro-retinopathy cellular and molecular events in both in vitro and in vivo models. In this review, we summarize the current understanding of the role of EVs in retinal (patho)physiology. Specifically, we will focus on disease-associated EV alterations in specific retinal diseases. Furthermore, we discuss the potential utility of EVs in diagnostic and therapeutic strategies for targeting retinal diseases.},
}
@article {pmid37181369,
year = {2023},
author = {Sannan, NS},
title = {Assessment of aggregate index of systemic inflammation and systemic inflammatory response index in dry age-related macular degeneration: a retrospective study.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1143045},
pmid = {37181369},
issn = {2296-858X},
abstract = {INTRODUCTION: Inflammation is known to contribute to the development of age-related macular degeneration (AMD). Several inflammatory indices derived from routine complete blood counts have been proposed as biomarkers in multiple disorders.<br><br>METHODS: In this study, clinical and laboratory data were retrospectively collected from medical records to assess the aggregate index of systemic inflammation (AISI) and the systemic inflammatory response index (SIRI) as potential biomarkers of systemic inflammation in patients with early diagnosis of dry AMD.<br><br>RESULTS: The study included 90 patients with dry AMD and 270 age/sex-matched patients with cataracts as a control group. There were no significant differences in the AISI and SIRI results between the cases and controls (p =&#x2009;0.16 and 0.19, respectively).<br><br>CONCLUSION: This suggests that AISI and SIRI may be inadequate metrics for AMD or lack sensitivity in detecting inflammatory changes. Exploring other routine blood markers may help to identify and prevent the early stages of AMD.},
}
@article {pmid37181079,
year = {2023},
author = {Leung, EH and Oh, DJ and Alderson, SE and Bracy, J and McLeod, M and Perez, LI and Bottini, A and Chin Yee, D and Mukkamala, K},
title = {Initial Real-World Experience with Faricimab in Treatment-Resistant Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1287-1293},
pmid = {37181079},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the initial efficacy and safety of intravitreal faricimab in eyes previously treated for neovascular age-related macular degeneration (nARMD).<br><br>PATIENTS AND METHODS: A retrospective review of all patients with nARMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) injections who received at least 3 intravitreal faricimab injections with at least 3 months of follow-up.<br><br>RESULTS: A total of 190 eyes were included. Patients received a mean of 34.2&#xb1;23 anti-VEGF injections over 182.41&#xb1;128 weeks prior to switching to faricimab. Patients then received a mean of 6.99&#xb1;2.3 faricimab injections with an average 34.88&#xb1;8.2 weeks of follow-up. The mean best corrected visual acuities improved from 0.33&#xb1;0.32 logMAR &#x2248;20/43 to 0.27&#xb1;0.32 logMAR &#x2248;20/37 (P=0.0022). The central subfield thickness (CST) improved from 312&#xb1;87&#x3bc;m to 287&#xb1;71&#x3bc;m (P<0.0001). At the last clinical visit, 24% had no subretinal fluid or intraretinal fluid on optical coherence tomography. The mean dosing interval between the last two consecutive faricimab injections (7.64&#xb1;6.2 weeks) was significantly longer than that for ranibizumab (5.16&#xb1;2.0 weeks, P<0.001) or aflibercept (5.57&#xb1;3.6 weeks, P<0.001). No patients developed idiopathic intraocular inflammation.<br><br>CONCLUSION: Intravitreal faricimab was associated with improved vision and CSTs, even in treatment-resistant nARMD eyes. The mean last dosing interval for faricimab was longer than for ranibizumab or aflibercept. No significant adverse events were directly attributed to faricimab during the study.},
}
@article {pmid37180540,
year = {2022},
author = {Mirghorbani, M and Riazi-Esfahani, H and Bazvand, F and Bahar, MM and Yaseri, M and Zarei, M},
title = {Impact of Coronavirus Disease 2019 Pandemic on the Epidemiology of Intravitreal Injections.},
journal = {Journal of current ophthalmology},
volume = {34},
number = {4},
pages = {442-447},
pmid = {37180540},
issn = {2452-2325},
abstract = {PURPOSE: To evaluate the epidemiologic pattern of intravitreal injections (IVIs) during Coronavirus Disease 2019 (COVID-19) pandemic.<br><br>METHODS: The records of patients receiving IVIs in two 12-month periods immediately before and after the beginning of the COVID-19 epidemic were included. Age, province of residency, indication, number of injections, and number of operating room (OR) visits were analyzed.<br><br>RESULTS: Compared to pre-COVID period, a 37.6% decrease in the number of patients receiving IVI in COVID period was seen (10518 vs. 6569). There was a parallel decrease in the number of OR visits (25590 vs. 15010: 41.4%) and injections (34508 vs. 19879: 42.4%). Regarding IVI indication, age-related macular degeneration (AMD) showed the highest decrease in IVI rate (46.3%) which was significantly higher than decrease in other indications (P < 0.001). Retinopathy of prematurity (ROP) patients showed no change after epidemic. Mean overall age in AMD group was the highest (67.7 &#xb1; 13.2 years) compared to other indication groups (excluding ROP) (P < 0.001); while the mean age of the other indications was not significantly different from each other (excluding ROP).<br><br>CONCLUSIONS: COVID pandemic decreased the number of IVIs significantly. While previous studies suggested that the AMD patients had the highest risk of visual loss due to failure to receive IVIs in a timely manner, this very same group showed the highest decrease in the IVI number after pandemic. The health systems should devise strategies to protect this most vulnerable group of patients in future similar crises.},
}
@article {pmid37180103,
year = {2023},
author = {Wooff, Y and Cioanca, AV and Wills, E and Chu-Tan, JA and Sekar, R and Natoli, R},
title = {Short exposure to photo-oxidative damage triggers molecular signals indicative of early retinal degeneration.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1088654},
pmid = {37180103},
issn = {1664-3224},
mesh = {Mice ; Animals ; *Retinal Degeneration/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; *Macular Degeneration ; *MicroRNAs/genetics/metabolism ; *Geographic Atrophy ; Oxidative Stress ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, currently affecting over 350 billion people globally. For the most prevalent late-stage form of this disease, atrophic AMD, there are no available prevention strategies or treatments, in part due to inherent difficulties in early-stage diagnosis. Photo-oxidative damage is a well-established model for studying inflammatory and cell death features that occur in late-stage atrophic AMD, however to date has not been investigated as a potential model for studying early features of disease onset. Therefore, in this study we aimed to determine if short exposure to photo-oxidative damage could be used to induce early retinal molecular changes and advance this as a potential model for studying early-stage AMD.<br><br>METHODS: C57BL/6J mice were exposed to 1, 3, 6, 12, or 24h photo-oxidative damage (PD) using 100k lux bright white light. Mice were compared to dim-reared (DR) healthy controls as well as mice which had undergone long periods of photo-oxidative damage (3d and 5d-PD) as known timepoints for inducing late-stage retinal degeneration pathologies. Cell death and retinal inflammation were measured using immunohistochemistry and qRT-PCR. To identify retinal molecular changes, retinal lysates were sent for RNA sequencing, following which bioinformatics analyses including differential expression and pathway analyses were performed. Finally, to investigate modulations in gene regulation as a consequence of degeneration, microRNA (miRNA) expression patterns were quantified using qRT-PCR and visualized using in situ hybridization.<br><br>RESULTS: Short exposure to photo-oxidative damage (1-24h-PD) induced early molecular changes in the retina, with progressive downregulation of homeostatic pathways including metabolism, transport and phototransduction observed across this time-course. Inflammatory pathway upregulation was observed from 3h-PD, preceding observable levels of microglia/macrophage activation which was noted from 6h-PD, as well as significant photoreceptor row loss from 24h-PD. Further rapid and dynamic movement of inflammatory regulator miRNA, miR-124-3p and miR-155-5p, was visualized in the retina in response to degeneration.<br><br>CONCLUSION: These results support the use of short exposure to photo-oxidative damage as a model of early AMD and suggest that early inflammatory changes in the retina may contribute to pathological features of AMD progression including immune cell activation and photoreceptor cell death. We suggest that early intervention of these inflammatory pathways by targeting miRNA such as miR-124-3p and miR-155-5p or their target genes may prevent progression into late-stage pathology.},
}
@article {pmid37179878,
year = {2023},
author = {Salzer, C and Samoila, L and Mortazavi Moshkenani, H and Samoila, O},
title = {Spiritual and religious perspectives in persons with visual impairment due to age-related macular degeneration.},
journal = {Frontiers in psychology},
volume = {14},
number = {},
pages = {1096215},
pmid = {37179878},
issn = {1664-1078},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is one of the global leading causes of severe vision loss. Patients suffering from AMD face complex spiritual and mental challenges that have an impact on the course of their disease, their quality of life, and their relationship with their surroundings.<br><br>METHODS: A survey was carried out using a 21-item questionnaire between August 2020 and June 2021 among 117 patients from different countries to investigate how spirituality, religion, and their way of practicing them affected the experiences and daily lives of patients suffering from AMD, and whether it helped them cope with the disease.<br><br>RESULTS: Our study concluded that spirituality and religion are important factors that facilitate patients' ability to cope with a progressive degenerative disease such as AMD. Patients who are religious are more at peace with having AMD. Practices that contribute to patients being at peace in accepting the disease are regular prayers or meditation. Spirituality and religion are important components that promote a healthier and happier emotional state and mental wellbeing. In particular, by believing that death is not the end, patients feel more hopeful, which helps in their adjustment to a seemingly hopeless health condition. A significant number of AMD patients desire to talk about God with the medical staff. The profile of such patients could be those believing in a higher power, praying often, participating in religious services, being worried about the loss of vision, and needing assistance in daily life.<br><br>DISCUSSION: An interdisciplinary and multidimensional team of medical health professionals including mental health workers and chaplains can be of great value in managing persons with AMD.},
}
@article {pmid37179553,
year = {2023},
author = {Wang, X and Wang, P},
title = {Spectral-domain optical coherence tomography combined with electroretinography in the assessment of conbercept for neovascular age-related macular degeneration: a preliminary study.},
journal = {Frontiers in neuroscience},
volume = {17},
number = {},
pages = {1179421},
pmid = {37179553},
issn = {1662-4548},
abstract = {OBJECTIVE: To observe the effect of three consecutive intravitreal injections of conbercept in the treatment of neovascular age-related macular degeneration (nAMD), to investigate the correlation between retinal anatomy and retinal function by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), to evaluate the short-term clinical efficacy of conbercept in the treatment of nAMD, and to explore the value of ERG as a predictor of treatment efficacy.<br><br>METHOD: A retrospective investigation was conducted on 36 patients (36 eyes) treated with intravitreal injections of conbercept at 0.5&#x2009;mg a month for three consecutive courses. Data collected included the best corrected visual acuity (BCVA), central retinal thickness (CRT), retinal pigment epithelium (RPE) elevation volume in 1&#x2009;mm-diameter (1RV), 3&#x2009;mm-diameter (3RV), and 6&#x2009;mm-diameter circles around the fovea (6RV), amplitude density and latency of the P1 wave in the multifocal electroretinography (mf-ERG) R1 ring and amplitude and latency in full-field electroretinography (ff-ERG) at baseline and monthly. The paired t test was used to compare the difference between pre- and posttreatment. Pearson correlation analysis was used to analyze the correlation between macular retinal structure and function. The difference was significant when p&#x2009;<&#x2009;0.05.<br><br>RESULTS: At 12&#x2009;weeks, the BCVA, CRT, 1RV, 3RV, 6RV, the P1 wave amplitude density of the mf-ERG R1 ring and the ff-ERG amplitude parameters were all significantly improved (p&#x2009;<&#x2009;0.001). The BCVA in logMAR was positively correlated with CRT; 1RV, 3RV, and 6RV were negatively correlated with the amplitude density and latency of the mf-ERG R1 ring P1 wave. There were no severe ocular or systemic complications during the follow-up period.<br><br>CONCLUSION: Conbercept is useful for the short-term treatment of nAMD. It can safely improve the visual acuity of affected eyes and restore the structure and function of the retina. ERG could serve as an objective indicator of function for evaluating the efficacy of and determining the need for retreatment during nAMD treatment.},
}
@article {pmid37846285,
year = {2022},
author = {Jin, K and Ye, J},
title = {Artificial intelligence and deep learning in ophthalmology: Current status and future perspectives.},
journal = {Advances in ophthalmology practice and research},
volume = {2},
number = {3},
pages = {100078},
pmid = {37846285},
issn = {2667-3762},
abstract = {BACKGROUND: The ophthalmology field was among the first to adopt artificial intelligence (AI) in medicine. The availability of digitized ocular images and substantial data have made deep learning (DL) a popular topic.<br><br>MAIN TEXT: At the moment, AI in ophthalmology is mostly used to improve disease diagnosis and assist decision-making aiming at ophthalmic diseases like diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), cataract and other anterior segment diseases. However, most of the AI systems developed to date are still in the experimental stages, with only a few having achieved clinical applications. There are a number of reasons for this phenomenon, including security, privacy, poor pervasiveness, trust and explainability concerns.<br><br>CONCLUSIONS: This review summarizes AI applications in ophthalmology, highlighting significant clinical considerations for adopting AI techniques and discussing the potential challenges and future directions.},
}
@article {pmid37641698,
year = {2022},
author = {Shahsuvaryan, ML},
title = {Carbonic anhydrase inhibitors in the management of macular edema: A review of the literature.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {11},
number = {1},
pages = {34-41},
pmid = {37641698},
issn = {2322-3219},
abstract = {BACKGROUND: Macular edema (ME) is a vision-threatening condition that commonly develops as a consequence of ocular diseases, including age-related macular degeneration, retinal vaso-occlusion of the central retinal vein and its branches, diabetic retinopathy, central serous chorioretinopathy, uveitis, retinitis pigmentosa, pseudophakia, ocular trauma, and drug toxicity. The treatment of ME remains challenging, although steroids and vascular endothelial growth factor inhibitors are available. Cost-effective therapy using a noninvasive administration route is required. This study aimed at reviewing the role of carbonic anhydrase inhibitors (CAIs) in the management of ME.<br><br>METHODS: A literature search was conducted using PubMed/MEDLINE and Google Scholar for studies from January 2000 to March 2022. The following keywords were used in various combinations: "macular edema", "carbonic anhydrase", "carbonic anhydrase inhibitors", "acetazolamide", "dorzolamide", and "brinzolamide".<br><br>RESULTS: Articles with high or medium clinical relevance were selected for this review. We found that multiple studies have demonstrated the relevance and efficacy rates of CAIs in the management of ME. Most published studies focused on acetazolamide and dorzolamide, with nearly all studies reporting therapeutic responses.<br><br>CONCLUSIONS: ME is the leading cause of vision loss and requires noninvasive and cost-effective pharmacotherapy. With progress in the understanding of ME, particularly the role of carbonic anhydrase as a key driver, CAIs are the focus of research. Further optimization of the choice of CAIs and retinal bioavailability, potentially with nanoparticle formulations, is required to enable the effective management of ME. Further research is warranted to address the therapeutic effects of CAIs in different formulations.},
}
@article {pmid37622161,
year = {2022},
author = {Kim, SY and Qian, H},
title = {Comparison between sodium iodate and lipid peroxide murine models of age-related macular degeneration for drug evaluation-a narrative review.},
journal = {Annals of eye science},
volume = {7},
number = {},
pages = {},
pmid = {37622161},
issn = {2520-4122},
support = {Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; ZIC EY000503/ImNIH/Intramural NIH HHS/United States ; },
abstract = {OBJECTIVE: In this review, non-transgenic models of age-related macular degeneration (AMD) are discussed, with focuses on murine retinal degeneration induced by sodium iodate and lipid peroxide (HpODE) as preclinical study platforms.<br><br>BACKGROUND: AMD is the most common cause of vision loss in a world with an increasingly aging population. The major phenotypes of early and intermediate AMD are increased drusen and autofluorescence, M&#xfc;ller glia activation, infiltrated subretinal microglia and inward moving retinal pigment epithelium cells. Intermediate AMD may progress to advanced AMD, characterized by geography atrophy and/or choroidal neovascularization. Various transgenic and non-transgenic animal models related to retinal degeneration have been generated to investigate AMD pathogenesis and pathobiology, and have been widely used as potential therapeutic evaluation platforms.<br><br>METHODS: Two retinal degeneration murine models induced by sodium iodate and HpODE are described. Distinct pathological features and procedures of these two models are compared. In addition, practical protocol and material preparation and assessment methods are elaborated.<br><br>CONCLUSION: Retina degeneration induced by sodium iodate and HpODE in mouse eye resembles many clinical aspects of human AMD and complimentary to the existent other animal models. However, standardization of procedure and assessment protocols is needed for preclinical studies. Further studies of HpODE on different routes, doses and species will be valuable for the future extensive use. Despite many merits of murine studies, differences between murine and human should be always considered.},
}
@article {pmid37641654,
year = {2021},
author = {Al-Namaeh, M},
title = {Common causes of visual impairment in the elderly.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {10},
number = {4},
pages = {191-200},
pmid = {37641654},
issn = {2322-3219},
abstract = {BACKGROUND: Aging is not a disease; rather, it is a process. As people age, visual impairment (VI) becomes more common. In 2010, the overall prevalence rate of vision impairment in all races was 25.66% in individuals aged ≥ 80 years, according to the estimate of the National Eye Institute at the National Institutes of Health. This review aimed to address the common causes of VI in the elderly.<br><br>METHODS: In this narrative review, an electronic search of the PubMed/MEDLINE database was conducted using "visual impairment" and "elderly" for the period between January 2010 and April 2021, to include randomized clinical trials and observational studies concerning VI in the elderly. The selected time period was chosen to provide an updated review.<br><br>RESULTS: The search yielded 2955 articles published over the period of more than 11 years. The relevant randomized clinical trials or observational studies were included and reviewed. Cataracts, refractive errors, open-angle glaucoma, age-related macular degeneration, and diabetic retinopathy were the most common age-related ocular disorders leading to VI if untreated in the elderly. The loss of visual acuity can adversely affect quality of life in the elderly. Difficulty with activities of daily living related to VI can lead to social isolation, depression, and anxiety. Loss of vision in the elderly is linked to an increased risk of falls, hip fracture, depression, and poor quality of life.<br><br>CONCLUSIONS: The most common causes of VI in the elderly are cataracts and refractive errors. VI in most ocular diseases is more prevalent in women than in men due to longer lifespan. The overall prevalence of the main causes of VI in the elderly is expected to increase; therefore, health policymakers should consider this when planning for the health-enhancement program of the population.},
}
@article {pmid37641652,
year = {2021},
author = {Venkatesh, P},
title = {Hypo-angiogenesis: a possible pathological factor in the development of dry age-related macular degeneration and a novel therapeutic target.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {10},
number = {4},
pages = {185-190},
pmid = {37641652},
issn = {2322-3219},
abstract = {BACKGROUND: Angiogenesis causes severe vision loss in patients with exudative or wet forms of age-related macular degeneration (AMD). The pathogenesis involves upregulation of several proangiogenic factors, particularly the vascular endothelial growth factor (VEGF). Contrary to the pathogenesis of exudative AMD, molecular events leading to the development of dry AMD remain unclear. Dry AMD is characterized by loss of the retinal pigment epithelium (RPE). The mechanism that triggers RPE cell loss remains unclear. Choriocapillaris development is absent in mice with RPE-specific deletion of VEGF. Moreover, in later life, background VEGF secretion promotes the survival of the RPE and maintains choriocapillaris integrity.<br><br>HYPOTHESIS: We hypothesized that reduced synthesis of VEGF (hypo-angiogenesis) or abnormalities in its receptors, VEGF receptor-1 (VEGFR1) and VEGFR2, may be involved in the pathogenesis of non-exudative AMD or dry AMD. If the concept of hypo-angiogenesis as a driver for dry AMD is proven, treatment with VEGF or induction of angiogenesis could be considered. Similar attempts at therapeutic angiogenesis have been actively investigated in cardiac and limb ischemia.<br><br>CONCLUSIONS: The reasons for a patient developing exudative AMD or dry AMD remain poorly understood. Nevertheless, targeting increased VEGF production in patients with exudative AMD using anti-VEGF drugs is highly efficacious in preserving vision. Similarly, dry AMD may be a manifestation of reduced VEGF synthesis (hypo-angiogenesis) and subsequent decreased RPE cell survival. Experimental studies exploring the possibility of reduced VEGF secretion and/or increased receptor resistance/abnormality could pave the way for clinical trials of angiogenesis to treat dry AMD.},
}
@article {pmid37383423,
year = {2022},
author = {Heravi, M and Rasoulinejad, SA},
title = {Potential of Müller Glial Cells in Regeneration of Retina; Clinical and Molecular Approach.},
journal = {International journal of organ transplantation medicine},
volume = {13},
number = {1},
pages = {50-59},
pmid = {37383423},
issn = {2008-6482},
abstract = {Retinal degenerative diseases are a group of heterogeneous eye diseases that affect a significant percentage of the world's population, i.e., age-related macular degeneration (AMD), diabetic retinopathy, retinitis pigmentosa (RP), and glaucoma. Regenerative medicines look for novel therapies for severe injuries or chronic diseases, e.g., retina degeneration. Müller glia is the only retinal glia type with a common embryonic origin, with retinal neurons derived from the neural crest. Also, the lack of neurons in the retina does not automatically regenerate. Therefore, Müller glial cells, which make up about 5% of retinal cells, are a potent source for retinal regeneration. Following the retinal damage, Müller glial cells dedifferentiate and re-enter the cell cycle, producing multipotent progenitor cells. This feature leads to applying Müller glial cells in the regeneration of the retina. This study reviews this feature's molecular and clinical approaches, focusing on the critical signaling pathways, generation and transplantation methods, and clinical and sub-clinical challenges.},
}
@article {pmid37641611,
year = {2021},
author = {Goker, YS and Demir, G},
title = {Comparison of optical coherence tomography angiography features in type 1 versus type 2 choroidal neovascular membranes secondary to age-related macular degeneration.},
journal = {Medical hypothesis, discovery &amp; innovation ophthalmology journal},
volume = {10},
number = {2},
pages = {67-73},
pmid = {37641611},
issn = {2322-3219},
abstract = {BACKGROUND: Optical coherence tomography angiography (OCTA) is an advanced imaging modality that provides high resolution images at the level of different retinal layers. This study aime to evaluate choroidal neovascular membranes (CNVMs) secondary to age-related macular degeneration (AMD) quantitatively and qualitatively, according to their classification, morphological features, and flow areas, using OCTA.<br><br>METHODS: In this descriptive, comparative, cross-sectional study, CNVMs were divided into 2 groups according to their classification as type 1 or type 2 neovascularization. Mied CNVMs were excluded from the study. The size (mm[2]) and the flow area (mm[2]) of the CNVMs were calculated via OCTA and the presence of the perivascular halo and loop anastomoses were analyzed. The morphological appearance of the CNVMs were classified as: medusa, sea-fan, lacy-wheel, glomerular, dead tree, and mature vascular networks.<br><br>RESULTS: Of the 85 eyes assessed for eligibility, 45 eyes of 34 individuals with CNVM were enrolled in this retrospective study. Twenty-eight eyes had type 1 and 17 eyes had type 2 CNVMs. The mean size and flow area were greater in type 1 than in type 2 CNVMs (mean [standard deviation], 6.69 [4.54] and 3.61 [3.56] mm[2] versus 3.04 [1.98] and 1.77 [1.62] mm[2]; P = 0.044 and 0.046, respectively). Among the 22 eyes with type 1 CNVMs and the 9 eyes with type 2 CNVMs, 31 eyes had exudative membranes. Among the eyes with exudative CNVMs, 22 eyes had a perivascular halo and 22 eyes had loop anastomoses; this was significantly more than in the non-exudative eyes (P = 0.042 and 0.041, respectively). The lacy-wheel (38.7%) and dead tree (71.4%) patterns were the most frequent morphological appearance of the CNVMs in the exudative and non-exudative membranes, respectively.<br><br>CONCLUSIONS: OCTA provides objective documantation about CNVMs. A perivascular dark halo around CNVMs could be a criterion to define exudative membranes activity.},
}
@article {pmid37672224,
year = {2021},
author = {Sohn, EH and Han, IC and Roos, BR and Faga, B and Luse, MA and Binkley, EM and Boldt, HC and Folk, JC and Russell, SR and Mullins, RF and Fingert, JH and Stone, EM and Scheetz, TE},
title = {Genetic Association between MMP9 and Choroidal Neovascularization in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {1},
number = {1},
pages = {100002},
pmid = {37672224},
issn = {2666-9145},
support = {P30 EY025580/EY/NEI NIH HHS/United States ; R01 EY026087/EY/NEI NIH HHS/United States ; R01 EY026547/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To evaluate the first association specific to exudative age-related macular degeneration (AMD) located near the matrix metalloproteinase 9 (MMP9) gene.<br><br>DESIGN: Genetic association study.<br><br>PARTICIPANTS: One thousand seven hundred twelve patients with AMD (672 nonexudative, 1040 exudative) of predominantly northern European descent seeking treatment at the University of Iowa Hospitals and Clinics.<br><br>METHODS: We reanalyzed the International AMD Genetics Consortium (IAMDGC) data to validate the association of polymorphisms near MMP9 with exudative AMD and to identify additional associated single nucleotide polymorphisms (SNPs), especially MMP9 coding sequence SNPs. We genotyped a cohort of 1712 AMD patients from Iowa with 3 SNPs identified with our analysis of the IAMDGC cohort using commercially available real-time quantitative polymerase chain reaction (PCR) assays. Firth regression was used to measure the association between MMP9 SNP genotypes and exudative AMD in our cohort of patients from Iowa. In addition, we developed a PCR-based assay to genotype the Iowa cohort at a short tandem repeat polymorphism (STRP) at the MMP9 locus.<br><br>MAIN OUTCOME MEASURES: Odds ratios and P values for exudative compared with nonexudative AMD patients in the Iowa cohort for MMP9 SNPs (rs4810482, rs17576, and rs17577) and STRP.<br><br>RESULTS: We identified 3 SNPs in the MMP9 locus (rs4810482, rs17576, and rs17577) that are highly associated with exudative AMD in patient cohorts of the IAMDGC. These MMP9 SNPs also are associated with exudative AMD in the cohort of 1712 AMD patients from Iowa (rs4810482: odds ratio [OR], 0.82; P&#xa0;= 0.010; rs17576: OR, 0.86; P&#xa0;= 0.046; and rs17577: OR, 0.80; P&#xa0;= 0.041). We also genotyped the cohort of AMD patients from Iowa at rs142450006, another MMP9 polymorphism that previously was associated with exudative AMD. We detected a 4bp STRP, (TTTC)n, at the rs142450006 locus that is highly polymorphic and associated significantly with exudative AMD (OR, 0.78; P&#xa0;= 0.016).<br><br>CONCLUSIONS: This study independently confirms and expands an association between the MMP9 locus and exudative AMD, further implicating a role for extracellular matrix abnormalities in choroidal neovascularization.},
}
@article {pmid37466960,
year = {2020},
author = {Rajagopal, AB and Slader, MJ and Osborn, MB},
title = {Build Your Own Eye: A Method for Teaching Ocular Anatomy and Pathophysiology.},
journal = {Journal of education &amp; teaching in emergency medicine},
volume = {5},
number = {3},
pages = {T42-T62},
pmid = {37466960},
issn = {2474-1949},
abstract = {AUDIENCE: Residents and medical students.<br><br>INTRODUCTION: The eye is a critical, but often neglected, part of medical learning. This team-based learning (TBL) module was developed for emergency medicine residents and medical students; however, is applicable to any learner who should know basic eye anatomy and pathology. Emergency medicine teams, primary care providers, and ophthalmologists are most likely to encounter ocular emergencies.1-3 These emergencies are uncommon but quite dire when they occur and can result in permanent disability and life-changing morbidity.2, 4 It is critical that medical practitioners who are exposed to these types of emergencies are well prepared to evaluate and treat them.To fully understand how pathology affects the eye, it is critical that learners understand the anatomy and physiology of the eye.5, 6 Many diagnoses are associated with specific parts of ocular anatomy;5, 6 therefore, teaching pathology in an anatomy-based lesson will help learners understand the physiology. This lesson teaches learners about physiology and pathology in a systemic, anatomically oriented way.<br><br>EDUCATIONAL OBJECTIVES: By the end of this session the participant will be able to:Describe basic anatomy of the eye.Build a basic model of the eye.Identify which diseases are associated with which parts of the eye.Identify the pathophysiology behind diseases of the eye.Name correct treatment for each disease.<br><br>EDUCATIONAL METHODS: The "build your own eye" lesson was taught as a classic team-based learning (cTBL) exercise. The modality of TBL with hands-on construction of an eye allow for social learning, competition and spatial learning related to anatomy. The creation of an eye allows residents to fully understand ocular anatomy which is not as evident when a two-dimensional paper image is used. Some learners need tactical stimuli for better understanding. This aspect of the exercise was focused on using alternative modalities to enhance spatial learning. These concepts are reinforced by the GRAT and IRAT portions of the exercise which tend to multiple choice learners. The fill-in the-blank aspect of the exercise requires recall and research to match the three-dimensional eye parts with pathology.<br><br>RESEARCH METHODS: Learners were given the opportunity to complete an anonymous survey. Verbal feedback was also obtained from learners during the lesson. The survey asked learners questions about the effectiveness and value of the exercise, whether the content was applicable to work in the emergency department, whether this exercise should be kept as a part of the curriculum, and whether there was any practice-changing information. Learners enjoyed the competitive aspects of the exercise and also noted that they felt much more comfortable with ocular anatomy and pathology after the lesson.<br><br>RESULTS: Learners felt that the ocular team-based learning module was effective in teaching more about the eye in an atypical way. Some learners felt that an explanation in advance of the eye building aspects of the project may have been helpful so they could have brought supplies from home. Other learners felt that they would not have brought supplies from home; thus no explanation was necessary.<br><br>DISCUSSION: Learners seemed to enjoy the experience. The competitive aspects of the TBL, where the eye models were judged for accuracy, creativity, and appearance as well as the correct answers on the worksheet, seemed to enhance learner enjoyment and engagement. Learners felt that enough time was provided for the exercise. While some learners would have preferred an explanation in advance of the project in order to bring supplies from home, others felt that this was not necessary. Educators should determine what would be preferred by their particular learning group for future implementations.<br><br>TOPICS: Eye lid, tear duct, cornea, conjunctiva, pupil, iris, lens, anterior chamber, vitreous body, posterior chamber, retina, macula, choroid, optic disc, optic nerve, retinal artery, retinal vein, blepharitis, hordeolum, chalazion, canaliculus, dacryocystitis, corneal abrasion, corneal ulcer, ultraviolet keratitis, herpes keratitis, astigmatism, bacterial conjunctivitis, viral conjunctivitis, episcleritis, globe rupture, iritis, uveitis, anterior uveitis, posterior uveitis, hypopyon, hyphema, acute angle closure glaucoma, congenital pupillary deformity, coloboma, globe rupture, nevus, essential iris atrophy, cataracts, presbyopia, myopia, hyperopia, traumatic iritis, iridocyclitis, ciliary body melanoma, vitreous degeneration, vitreous hemorrhage, endophthalmitis, macular degeneration, retinal detachment, choroid nevus, choroid detachment, papilledema, optic nerve glioma, optic nerve meningioma, anterior ischemic optic neuropathy, retinal artery occlusion, retinal vein occlusion.},
}
@article {pmid37287474,
year = {2017},
author = {Bulson, R and Faridi, A},
title = {Normotensive Glaucoma Follow-Up with Incidental Finding of Choroidal Neovascular Membrane: a Teaching Case Report.},
journal = {Optometric education},
volume = {42},
number = {17},
pages = {16-22},
pmid = {37287474},
issn = {1933-8880},
support = {P30 EY010572/EY/NEI NIH HHS/United States ; },
abstract = {Behind cataracts, glaucoma is the second leading cause of blindness worldwide. Patients with glaucoma are followed at regular intervals for testing to confirm stability of the disease; however, providers may need to divert from planned glaucoma testing when clinical findings suggest progression of comorbid ophthalmic conditions. This case report describes a patient presenting for a routine glaucoma follow-up appointment who was subsequently diagnosed with an acute choroidal neovascular membrane due to conversion from non-neovascular to neovascular age-related macular degeneration. The case highlights the management of normotensive glaucoma and both non-neovascular and neovascular macular degeneration.},
}
@article {pmid37664082,
year = {2014},
author = {Iida, T and Narimatsu, A and Adachi, K and Wang, EC},
title = {Anti-vascular Endothelial Growth Factor Outpatient Treatment Patterns in Patients with Exudative Age-related Macular Degeneration from a Japanese Hospital Claims Database.},
journal = {Journal of health economics and outcomes research},
volume = {2},
number = {1},
pages = {41-52},
doi = {10.36469/9887},
pmid = {37664082},
issn = {2327-2236},
abstract = {Purpose: To identify outpatient treatment patterns of patients with exudative age-related macular degeneration (AMD) who received approved anti-vascular endothelial growth factor (VEGF) therapy, using real-world data from hospitals in Japan. Methods: A hospital claims database was retrospectively reviewed for patients diagnosed with exudative AMD who were treated with anti-VEGF therapy in the outpatient setting between January 2010 and December 2012. Within a treatment period of at least 12 months, the frequency of anti-VEGF injections and AMD-related visits, and time intervals between AMD-related visits and anti-VEGF injections were captured for patients who had neither cataracts nor glaucoma. "Loading dose regimen" was defined as the first 2 or 3 monthly doses and "PRN maintenance regimen" (where PRN=pro re nata) was defined as the entire period of time after the loading doses had been administered. Results: Claims data were collected from a total of 219 patients from 13 of 126 hospitals: 217 treated with ranibizumab (8 received pegaptanib as well), 2 with aflibercept. Of these, 68 patients were treated for at least 12 months (all with ranibizumab PRN), and 29 had neither cataracts nor glaucoma and were included in the treatment pattern analysis. These 29 patients received a mean of 3.8 injections in the first 12 months and another 2.5 injections in the second 12 months of treatment. The average number of all outpatient visits was 16.1 in the first 12 months and 13.7 in the second 12 months, and an average of 11.6 days elapsed between injections and the previous outpatient monitoring visits using a PRN schedule. Conclusion: In a real-world setting in Japan, anti-VEGF PRN injections are administered less frequently than in clinical trials, and with time between monitoring and re-injection visits. Nonetheless, patients still visit the hospital frequently, which can significantly burden patients, caregivers, and healthcare providers.},
}
@article {pmid37179017,
year = {2023},
author = {Loewenstein, A and Czumbel, N and Ernest, J and Dusová, J and Pearlman, J and Nowosielska, A},
title = {Randomized Trial of Biosimilar XSB-001 versus Reference Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {9},
pages = {753-761},
doi = {10.1016/j.oret.2023.05.005},
pmid = {37179017},
issn = {2468-6530},
mesh = {Humans ; Female ; Aged ; Male ; Ranibizumab ; Angiogenesis Inhibitors ; *Biosimilar Pharmaceuticals/therapeutic use ; Visual Acuity ; *Macular Degeneration/diagnosis/drug therapy/chemically induced ; },
abstract = {OBJECTIVE: To evaluate the efficacy, safety, and immunogenicity of a ranibizumab biosimilar candidate (XSB-001) versus reference product (Lucentis) for neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Phase III, multicenter, randomized, double-masked, parallel-group study.<br><br>PARTICIPANTS: Patients with nAMD.<br><br>METHODS: Eligible patients were randomized (1:1) to receive intravitreal injections of XSB-001 or reference ranibizumab (0.5 mg [0.05 ml]) in the study eye once every 4 weeks for 52 weeks. Efficacy and safety assessments continued through 52 weeks of treatment.<br><br>MAIN OUTCOME MEASURES: Primary end point was change from baseline in best-corrected visual acuity (BCVA) by ETDRS letters at week 8. Biosimilarity was concluded if the 2-sided 90% confidence interval (CI) (United States) or 95% CI (rest of world) for the difference in least-squares (LS) mean change in BCVA at week 8 between treatment groups was within the predefined equivalence margin of &#xb1; 3.5 letters.<br><br>RESULTS: In total, 582 patients (n&#xa0;= 292 XSB-001, n&#xa0;= 290 reference ranibizumab) were randomized. Mean age was 74.1 years, most patients (85.2%) were White, and 55.8% were women. Mean BCVA score at baseline was 61.7 and 61.5 ETDRS letters in the XSB-001 and reference ranibizumab groups, respectively. At week 8, the LS mean (standard error [SE]) change in BCVA from baseline was 4.6 (0.5) ETDRS letters in the XSB-001 group and 6.4 (0.5) letters in the reference ranibizumab group (LS mean [SE] treatment difference:&#xa0;-1.8 [0.7] ETDRS letters; 90% CI,&#xa0;-2.9 to&#xa0;-0.7; 95% CI,&#xa0;-3.1 to&#xa0;-0.5). The 90% CI and 95% CI for LS mean difference in change from baseline were within the predefined equivalence margin. At week 52, LS mean (SE) change in BCVA was 6.4 (0.8) and 7.8 (0.8) letters, respectively (LS mean [SE] treatment difference,&#xa0;-1.5 [1.1] ETDRS letters; 90% CI,&#xa0;-3.3 to 0.4; 95% CI,&#xa0;-3.6 to 0.7). There were no clinically meaningful differences between treatments in anatomical, safety, or immunogenicity end points through week&#xa0;52.<br><br>CONCLUSIONS: XSB-001 demonstrated biosimilarity to reference ranibizumab in patients with nAMD. Treatment with XSB-001 for 52 weeks was generally safe and well tolerated, with a safety profile similar to the reference product.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37178941,
year = {2023},
author = {Del Amo, EM and Bishop, PN and Godia, P and Aarons, L},
title = {Towards a population pharmacokinetic/pharmacodynamic model of anti-VEGF therapy in patients with age-related macular degeneration.},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V},
volume = {188},
number = {},
pages = {78-88},
doi = {10.1016/j.ejpb.2023.05.007},
pmid = {37178941},
issn = {1873-3441},
mesh = {Humans ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Treatment Outcome ; Intravitreal Injections ; Bevacizumab ; *Macular Degeneration/drug therapy ; Ranibizumab ; *Wet Macular Degeneration/chemically induced/drug therapy ; },
abstract = {PURPOSE: To develop a population pharmacokinetic/pharmacodynamic model (popPKPD) of intravitreal bevacizumab treatment for neovascular age-related macular degeneration (nAMD) patients to learn about the PK/PD relationship and utilise it for dosing regimen decisions on future nAMD patients.<br><br>METHODS: The Greater Manchester Avastin for Neovascularisation (GMAN) randomised clinical trial data was retrospectively utilised, and the best-corrected visual acuity (BCVA) and central macular retinal thickness (CRT, measured by optical coherence tomography) were the PD inputs to the model. Using the nonlinear mixed-effects method, the best PKPD structural model was investigated, and the clinical significance of the two different dosing treatment regimens (as-needed versus routine) was evaluated.<br><br>RESULTS: A structural model to describe the change of BCVA from the baseline of nAMD patients was successfully obtained based on the turnover PD model concept (drug stimulates the "visual acuity response production"). The popPKPD model and simulation indicate that the routine regimen protocol improves patient visual outcome compared to the as-needed protocol. For the change in CRT, the turnover structural PKPD model was too demanding to fit to the given clinical data.<br><br>CONCLUSIONS: This is the first popPKPD attempt in nAMD treatment that shows the potential of this strategy to understand/inform the dosing regimen. Clinical trials with richer PD data will provide the means to build more robust models.},
}
@article {pmid37176706,
year = {2023},
author = {Zbrzezny, AM and Grzybowski, AE},
title = {Deceptive Tricks in Artificial Intelligence: Adversarial Attacks in Ophthalmology.},
journal = {Journal of clinical medicine},
volume = {12},
number = {9},
pages = {},
pmid = {37176706},
issn = {2077-0383},
abstract = {The artificial intelligence (AI) systems used for diagnosing ophthalmic diseases have significantly progressed in recent years. The diagnosis of difficult eye conditions, such as cataracts, diabetic retinopathy, age-related macular degeneration, glaucoma, and retinopathy of prematurity, has become significantly less complicated as a result of the development of AI algorithms, which are currently on par with ophthalmologists in terms of their level of effectiveness. However, in the context of building AI systems for medical applications such as identifying eye diseases, addressing the challenges of safety and trustworthiness is paramount, including the emerging threat of adversarial attacks. Research has increasingly focused on understanding and mitigating these attacks, with numerous articles discussing this topic in recent years. As a starting point for our discussion, we used the paper by Ma et al. "Understanding Adversarial Attacks on Deep Learning Based Medical Image Analysis Systems". A literature review was performed for this study, which included a thorough search of open-access research papers using online sources (PubMed and Google). The research provides examples of unique attack strategies for medical images. Unfortunately, unique algorithms for attacks on the various ophthalmic image types have yet to be developed. It is a task that needs to be performed. As a result, it is necessary to build algorithms that validate the computation and explain the findings of artificial intelligence models. In this article, we focus on adversarial attacks, one of the most well-known attack methods, which provide evidence (i.e., adversarial examples) of the lack of resilience of decision models that do not include provable guarantees. Adversarial attacks have the potential to provide inaccurate findings in deep learning systems and can have catastrophic effects in the healthcare industry, such as healthcare financing fraud and wrong diagnosis.},
}
@article {pmid37176602,
year = {2023},
author = {Dolar-Szczasny, J and Barańska, A and Rejdak, R},
title = {Evaluating the Efficacy of Teleophthalmology in Delivering Ophthalmic Care to Underserved Populations: A Literature Review.},
journal = {Journal of clinical medicine},
volume = {12},
number = {9},
pages = {},
pmid = {37176602},
issn = {2077-0383},
abstract = {Technological advancement has brought commendable changes in medicine, advancing diagnosis, treatment, and interventions. Telemedicine has been adopted by various subspecialties including ophthalmology. Over the years, teleophthalmology has been implemented in various countries, and continuous progress is being made in this area. In underserved populations, due to socioeconomic factors, there is little or no access to healthcare facilities, and people are at higher risk of eye diseases and vision impairment. Transportation is the major hurdle for these people in obtaining access to eye care in the main hospitals. There is a dire need for accessible eye care for such populations, and teleophthalmology is the ray of hope for providing eye care facilities to underserved people. Numerous studies have reported the advantages of teleophthalmology for rural populations such as being cost-effective, timesaving, reliable, efficient, and satisfactory for patients. Although it is being practiced in urban populations, for rural populations, its benefits amplify. However, there are certain obstacles as well, such as the cost of equipment, lack of steady electricity and internet supply in rural areas, and the attitude of people in certain regions toward acceptance of teleophthalmology. In this review, we have discussed in detail eye health in rural populations, teleophthalmology, and its effectiveness in rural populations of different countries.},
}
@article {pmid37176491,
year = {2023},
author = {Nawash, B and Ong, J and Driban, M and Hwang, J and Chen, J and Selvam, A and Mohan, S and Chhablani, J},
title = {Prognostic Optical Coherence Tomography Biomarkers in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {9},
pages = {},
pmid = {37176491},
issn = {2077-0383},
abstract = {Optical coherence tomography has revolutionized the diagnosis and management of neovascular age-related macular degeneration. OCT-derived biomarkers have the potential to further guide therapeutic advancements with anti-vascular endothelial growth factor; however, the clinical convergence between these two tools remains suboptimal. Therefore, the aim of this review of literature was to examine the current data on OCT biomarkers and their prognostic value. Thirteen biomarkers were analyzed, and retinal fluid had the strongest-reported impact on clinical outcomes, including visual acuity, clinic visits, and anti-VEGF treatment regimens. In particular, intra-retinal fluid was shown to be associated with poor visual outcomes. Consistencies in the literature with regard to these OCT prognostic biomarkers can lead to patient-specific clinical decision making, such as early-initiated treatment and proactive monitoring. An integrated analysis of all OCT components in combination with new efforts toward automated analysis with artificial intelligence has the potential to further improve the role of OCT in nAMD therapy.},
}
@article {pmid37175752,
year = {2023},
author = {Samoilă, L and Voștinaru, O and Dinte, E and Bodoki, AE and Iacob, BC and Bodoki, E and Samoilă, O},
title = {Topical Treatment for Retinal Degenerative Pathologies: A Systematic Review.},
journal = {International journal of molecular sciences},
volume = {24},
number = {9},
pages = {},
pmid = {37175752},
issn = {1422-0067},
support = {CCCDI - UEFISCDI, project number PN-III-P2-2.1-PED-2019-1387, within PNCDI III//Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii/ ; },
mesh = {Humans ; *Retinal Diseases/drug therapy ; *Macular Edema/drug therapy ; Retina ; *Diabetic Retinopathy/drug therapy ; Administration, Topical ; Pharmaceutical Preparations ; },
abstract = {The topical administration of medicines is the preferred route in ocular therapy, at least for the anterior segment of the eye. However, the eye's inherent functional and biological barriers all work against the active pharmaceutical ingredient (API) to efficiently reach the targeted retinal structures. The main objective of this article is to offer a systematic review of the scientific literature in recent years, focusing on the latest developments of topical treatment intended for retinal degenerative diseases. Database search returned 102 clinical studies, focused on topical treatment for age macular degeneration, macular edemas (in diabetic retinopathy, surgery related or in retinal dystrophies) or glaucoma. After the exclusion of low-powered studies and those combining vitreo-retinal surgery, 35 articles remained for analysis. Currently, the topical treatment of retinal degenerative diseases is limited by the difficulty to deliver effective drug concentrations to the posterior eye structures. However, in the case of drug classes like NSAIDs, the presence of certain molecular and metabolic features for specific representatives makes the topical administration currently feasible in several clinical contexts. For other drug classes, either a fine-tuning of the API's pharmacokinetic profile or the use of more advanced formulation strategies, such as rationally designed nanostructured drugs and vehicles, crystalline polymorphs or supramolecular complexes, could bring the much awaited breakthrough for a more predictable and controlled delivery towards the retinal structures and could eventually be employed in the future for the development of more effective ways of delivering drugs to the posterior eye, with the ultimate goal of improving their clinical efficacy.},
}
@article {pmid37175646,
year = {2023},
author = {Dörschmann, P and Thalenhorst, T and Seeba, C and Tischhöfer, MT and Neupane, S and Roider, J and Alban, S and Klettner, A},
title = {Comparison of Fucoidans from Saccharina latissima Regarding Age-Related Macular Degeneration Relevant Pathomechanisms in Retinal Pigment Epithelium.},
journal = {International journal of molecular sciences},
volume = {24},
number = {9},
pages = {},
pmid = {37175646},
issn = {1422-0067},
support = {01/20//Helmut-Ecker foundation/ ; },
mesh = {Interleukin-8/metabolism ; Swine ; Retinal Pigment Epithelium/metabolism ; Edible Seaweeds ; Hydrogen Peroxide/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Humans ; *Laminaria/metabolism ; Animals ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {Fucoidans from brown algae are described as anti-inflammatory, antioxidative, and antiangiogenic. We tested two Saccharina latissima fucoidans (SL-FRO and SL-NOR) regarding their potential biological effects against age-related macular degeneration (AMD). Primary porcine retinal pigment epithelium (RPE), human RPE cell line ARPE-19, and human uveal melanoma cell line OMM-1 were used. Cell survival was assessed in tetrazolium assay (MTT). Oxidative stress assays were induced with erastin or H2O2. Supernatants were harvested to assess secreted vascular endothelial growth factor A (VEGF-A) in ELISA. Barrier function was assessed by measurement of trans-epithelial electrical resistance (TEER). Protectin (CD59) and retinal pigment epithelium-specific 65 kDa protein (RPE65) were evaluated in western blot. Polymorphonuclear elastase and complement inhibition assays were performed. Phagocytosis of photoreceptor outer segments was tested in a fluorescence assay. Secretion and expression of proinflammatory cytokines were assessed with ELISA and real-time PCR. Fucoidans were chemically analyzed. Neither toxic nor antioxidative effects were detected in ARPE-19 or OMM-1. Interleukin 8 gene expression was slightly reduced by SL-NOR but induced by SL-FRO in RPE. VEGF secretion was reduced in ARPE-19 by SL-FRO and in RPE by both fucoidans. Polyinosinic:polycytidylic acid induced interleukin 6 and interleukin 8 secretion was reduced by both fucoidans in RPE. CD59 expression was positively influenced by fucoidans, and they exhibited a complement and elastase inhibitory effect in cell-free assay. RPE65 expression was reduced by SL-NOR in RPE. Barrier function of RPE was transiently reduced. Phagocytosis ability was slightly reduced by both fucoidans in primary RPE but not in ARPE-19. Fucoidans from Saccharina latissima, especially SL-FRO, are promising agents against AMD, as they reduce angiogenic cytokines and show anti-inflammatory and complement inhibiting properties; however, potential effects on gene expression and RPE functions need to be considered for further research.},
}
@article {pmid37174984,
year = {2023},
author = {Krytkowska, E and Grabowicz, A and Safranow, K and Machalińska, A},
title = {Does the Presence of the Cilioretinal Artery Affect the Incidence, Clinical Picture and Progression of Age-Related Macular Degeneration?.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {9},
pages = {},
pmid = {37174984},
issn = {2075-4418},
support = {STRATEGMED1/234261/2NCBR/2014//Polish National Centre for Research and Development/ ; },
abstract = {The aims of this study were to analyze the relationship between the presence of the cilioretinal artery (CRA) and the incidence, severity and progression of age-related macular degeneration (AMD) and to estimate the influence of the CRA on choroidal and retinal parameters. A total of 287 patients with AMD and 110 healthy controls were enrolled in the study. CRA occurrence was determined using color fundus images. AMD progression was assessed after 3 years. There was no difference in the incidence of CRA between the AMD and control groups (23.34% vs. 24.55%; p = 0.8). Lower-stage AMD was more frequently observed in eyes with the CRA than in eyes without the artery (p = 0.016). The CRA did not influence disease progression (p = 0.79). The CRA did not influence retinal and choroidal thickness and volume parameters or the retinal vessel caliber and functionality in either the AMD or control groups. There was no relationship between CRA presence and CFH Y402H and ARMS2 A69S risk variants. The results did not show a protective effect of the CRA on the incidence and progression of AMD. The CRA may affect the severity of AMD; however, the mechanism of this phenomenon is unclear.},
}
@article {pmid37174708,
year = {2023},
author = {Navneet, S and Brandon, C and Simpson, K and Rohrer, B},
title = {Exploring the Therapeutic Potential of Elastase Inhibition in Age-Related Macular Degeneration in Mouse and Human.},
journal = {Cells},
volume = {12},
number = {9},
pages = {},
pmid = {37174708},
issn = {2073-4409},
support = {I01 BX003050/BX/BLRD VA/United States ; I01 RX000444/RX/RRD VA/United States ; R01 HS028284/HS/AHRQ HHS/United States ; R01 EY030072/EY/NEI NIH HHS/United States ; IK6 BX004858/BX/BLRD VA/United States ; },
mesh = {Humans ; Mice ; Animals ; Pancreatic Elastase ; *Macular Degeneration/metabolism ; Bruch Membrane/metabolism ; Choroid/metabolism ; Retina/metabolism ; *Choroidal Neovascularization/drug therapy/metabolism ; High-Temperature Requirement A Serine Peptidase 1 ; },
abstract = {Abnormal turnover of the extracellular matrix (ECM) protein elastin has been linked to AMD pathology. Elastin is a critical component of Bruch's membrane (BrM), an ECM layer that separates the retinal pigment epithelium (RPE) from the underlying choriocapillaris. Reduced integrity of BrM's elastin layer corresponds to areas of choroidal neovascularization (CNV) in wet AMD. Serum levels of elastin-derived peptides and anti-elastin antibodies are significantly elevated in AMD patients along with the prevalence of polymorphisms of genes regulating elastin turnover. Despite these results indicating significant associations between abnormal elastin turnover and AMD, very little is known about its exact role in AMD pathogenesis. Here we report on results that suggest that elastase enzymes could play a direct role in the pathogenesis of AMD. We found significantly increased elastase activity in the retinas and RPE cells of AMD mouse models, and AMD patient-iPSC-derived RPE cells. A1AT, a protease inhibitor that inactivates elastase, reduced CNV lesion sizes in mouse models. A1AT completely inhibited elastase-induced VEGFA expression and secretion, and restored RPE monolayer integrity in ARPE-19 monolayers. A1AT also mitigated RPE thickening, an early AMD phenotype, in HTRA1 overexpressing mice, HTRA1 being a serine protease with elastase activity. Finally, in an exploratory study, examining archival records from large patient data sets, we identified an association between A1AT use, age and AMD risk. Our results suggest that repurposing A1AT may have therapeutic potential in modifying the progression to AMD.},
}
@article {pmid37173428,
year = {2023},
author = {Khanani, AM and Aziz, AA and Khan, H and Gupta, A and Mojumder, O and Saulebayeva, A and Abbey, AM and Almeida, DRP and Avery, RL and Banda, HK and Barakat, MR and Bhandari, R and Chang, EY and Haug, SJ and London, NJS and Mein, L and Sheth, VS and Wolfe, JD and Singer, MA and Danzig, CJ},
title = {The real-world efficacy and safety of faricimab in neovascular age-related macular degeneration: the TRUCKEE study - 6 month results.},
journal = {Eye (London, England)},
volume = {37},
number = {17},
pages = {3574-3581},
pmid = {37173428},
issn = {1476-5454},
mesh = {Humans ; *Angiogenesis Inhibitors/adverse effects ; Retrospective Studies ; Treatment Outcome ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Inflammation ; },
abstract = {BACKGROUND/OBJECTIVE: Investigate real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD).<br><br>SUBJECTS/METHODS: Multicenter, retrospective chart review was conducted on patients treated with faricimab for nAMD from February 2022 to September 2022. Collected data includes background demographics, treatment history, best-corrected visual acuity (BCVA), anatomic changes, and adverse events as safety markers. The main outcome measures are changes in BCVA, changes in central subfield thickness (CST) and adverse events. Secondary outcome measures included treatment intervals and presence of retinal fluid.<br><br>RESULTS: After one injection of faricimab, all eyes (n&#x2009;=&#x2009;376), previously-treated (n&#x2009;=&#x2009;337) and treatment-na&#xef;ve (n&#x2009;=&#x2009;39) eyes demonstrated a&#x2009;+&#x2009;1.1 letter (p&#x2009;=&#x2009;0.035), a&#x2009;+&#x2009;0.7 letter (p&#x2009;=&#x2009;0.196) and a&#x2009;+&#x2009;4.9 letter (p&#x2009;=&#x2009;0.076) improvement in BCVA, respectively, and a&#x2009;-&#x2009;31.3&#x2009;&#x3bc;M (p&#x2009;<&#x2009;0.001), a&#x2009;-&#x2009;25.3&#x2009;&#x3bc;M (p&#x2009;<&#x2009;0.001) and a&#x2009;-&#x2009;84.5&#x2009;&#x3bc;M (p&#x2009;<&#x2009;0.001) reduction in CST, respectively. After three injections of faricimab, all eyes (n&#x2009;=&#x2009;94), previously-treated (n&#x2009;=&#x2009;81) and treatment-na&#xef;ve (n&#x2009;=&#x2009;13) eyes demonstrated a&#x2009;+&#x2009;3.4 letter (p&#x2009;=&#x2009;0.03), a&#x2009;+&#x2009;2.7 letter (p&#x2009;=&#x2009;0.045) and a&#x2009;+&#x2009;8.1 letter (p&#x2009;=&#x2009;0.437) improvement in BCVA, and a&#x2009;-&#x2009;43.4&#x2009;&#x3bc;M (p&#x2009;<&#x2009;0.001), a&#x2009;-&#x2009;38.1&#x2009;&#x3bc;M (p&#x2009;<&#x2009;0.001) and a&#x2009;-&#x2009;80.1&#x2009;&#x3bc;M (p&#x2009;<&#x2009;0.204) reduction in CST, respectively. One case of intraocular inflammation was observed after four injections of faricimab and resolved with topical steroids. One case of infectious endophthalmitis was treated with intravitreal antibiotics and resolved.<br><br>CONCLUSIONS: Faricimab has demonstrated improvement or maintenance of visual acuity for patients with nAMD, along with rapid improvement of anatomical parameters. It has been well-tolerated with low incidence of treatable intraocular inflammation. Future data will continue to investigate faricimab for real-world patients with nAMD.},
}
@article {pmid37172783,
year = {2023},
author = {Hashida, N and Nishida, K},
title = {Recent advances and future prospects: Current status and challenges of the intraocular injection of drugs for vitreoretinal diseases.},
journal = {Advanced drug delivery reviews},
volume = {198},
number = {},
pages = {114870},
doi = {10.1016/j.addr.2023.114870},
pmid = {37172783},
issn = {1872-8294},
mesh = {Humans ; Pharmaceutical Preparations ; *Eye Diseases/drug therapy ; Drug Delivery Systems ; Eye ; Injections, Intraocular ; },
abstract = {Effective drug therapy for vitreoretinal disease is a major challenge in the field of ophthalmology; various protective systems, including anatomical and physiological barriers, complicate drug delivery to precise targets. However, as the eye is a closed cavity, it is an ideal target for local administration. Various types of drug delivery systems have been investigated that take advantage of this aspect of the eye, enhancing ocular permeability and optimizing local drug concentrations. Many drugs, mainly anti-VEGF drugs, have been evaluated in clinical trials and have provided clinical benefit to many patients. In the near future, innovative drug delivery systems will be developed to avoid frequent intravitreal administration of drugs and maintain effective drug concentrations for a long period of time. Here, we review the published literature on various drugs and administration routes and current clinical applications. Recent advances in drug delivery systems are discussed along with future prospects.},
}
@article {pmid37171557,
year = {2023},
author = {Yanagi, Y and Takahashi, K and Iida, T and Gomi, F and Morii, J and Kunikane, E and Sakamoto, T},
title = {Cost-Effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration in Japan.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {4},
pages = {2005-2021},
pmid = {37171557},
issn = {2193-8245},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is the world's leading cause of blindness in elderly people. While anti-vascular endothelial growth factor (VEGF) treatments are used as the first option for patients with nAMD, they are generally expensive and need repeated injections. This study aimed to evaluate the cost-effectiveness of anti-VEGF therapies, focusing on the newly launched ranibizumab biosimilar (RBZ BS) in patients with nAMD from a Japanese societal perspective.<br><br>METHODS: A Markov model was developed to simulate the lifetime transitions of a cohort of treatment-na&#xef;ve patients with nAMD through health states that were based on the involvement of nAMD (single eye vs. both eyes), the treatment status of the patients, and decimal best-corrected visual acuity. The model compared RBZ BS with branded RBZ, aflibercept (AFL), and AFL as loading dose switched to RBZ BS in maintenance in the treat-and-extend (TAE) regimen (RBZ TAE, AFL TAE, and AFL to RBZ BS TAE, respectively), and with branded RBZ in the pro re nata (PRN) regimen, as well as best supportive care (BSC). All processes were validated by five clinical experts.<br><br>RESULTS: When TAE regimens were compared, RBZ BS was dominant (higher quality-adjusted life-years (QALYs) and lower total cost) to AFL TAE and AFL to RBZ TAE. The result was robust regardless of whether the clinical data were taken from the direct head-to-head clinical trial or from indirect treatment comparison. RBZ BS TAE was cost-saving compared to RBZ TAE. RBZ BS TAE was estimated to be dominant to BSC owing to a lower societal cost. Like TAE regimens, RBZ BS was cost-saving compared to RBZ PRN and was dominant to BSC in PRN regimens.<br><br>CONCLUSION: This study suggests that RBZ BS is dominant to other anti-VEGF treatments in patients with nAMD in both TAE and PRN regimens and BSC from a Japanese societal perspective.},
}
@article {pmid37170250,
year = {2023},
author = {Goyal, S and Singh, K and Uppal, A and Vanita, V},
title = {A nonsense mutation in C8orf37 linked with retinitis pigmentosa, early macular degeneration, cataract, and myopia in an arRP family from North India.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {210},
pmid = {37170250},
issn = {1471-2415},
support = {BT/IN/German/13/VK/2010 IND 10/036//Department of Biotechnology, Ministry of Science and Technology, India/ ; No.3/1/2(4)/OPH/2016/NCD-II//Indian Council of Medical Research/ ; },
mesh = {Humans ; *Cataract/genetics/diagnosis ; Codon, Nonsense ; DNA Mutational Analysis ; Eye Proteins/genetics ; *Macular Degeneration ; Mutation ; *Myopia/genetics ; Pedigree ; Proteins/genetics ; *Retinitis Pigmentosa/genetics/diagnosis ; },
abstract = {OBJECTIVE: This study aimed at identifying the underlying genetic defect in a consanguineous autosomal recessive retinitis pigmentosa (arRP) (RP-1175) family having RP with early macular degeneration, cataract, and myopia.<br><br>METHODS: Whole-exome sequencing (WES) was performed on the DNA of the proband, and variants observed were validated in the rest of the affected and unaffected family members by Sanger sequencing. Different bioinformatics tools were applied to access the pathogenicity of the observed variant.<br><br>RESULTS: A nonsense mutation i.e., c.555G&#x2009;>&#x2009;A (p.Trp185Ter) in C8orf37 in homozygous form, has been identified that segregated with the disease in the affected members. c.555G&#x2009;>&#x2009;A was absent in unaffected family members and in 107 ethnically matched controls, therefore ruling out its possibility of being a polymorphism.<br><br>CONCLUSIONS: Present study identifies a nonsense mutation (c.555G&#x2009;>&#x2009;A) at codon 185 in C8orf37 linked with arRP, early macular degeneration, posterior subcapsular cataract, and myopia. The identical mutation has previously been reported in a Pakistani family with isolated RP and in a Chinese family with RP and macular degeneration. This variable expressivity of the identified mutation c.555G&#x2009;>&#x2009;A in C8orf37 in the analyzed Indian family may be attributed to the presence of the modifier alleles. Also, Trp185 might be a mutation hotspot in Asian arRP patients and in the future, p.Trp185Ter in C8orf37 may be tested during initial screening in arRP cases especially belonging to a similar population.},
}
@article {pmid37170013,
year = {2023},
author = {Enoch, J and Ghulakhszian, A and Sekhon, M and Crabb, DP and Taylor, DJ and Dinah, C},
title = {Exploring patient acceptability of emerging intravitreal therapies for geographic atrophy: A mixed-methods study.},
journal = {Eye (London, England)},
volume = {37},
number = {17},
pages = {3634-3642},
pmid = {37170013},
issn = {1476-5454},
support = {Higher Education Innovation Fund//UoL | City, University of London (City, UoL)/ ; },
mesh = {Humans ; Female ; Male ; *Geographic Atrophy/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Visual Acuity ; *Wet Macular Degeneration/drug therapy/complications ; Intravitreal Injections ; },
abstract = {BACKGROUND/OBJECTIVES: The acceptability of emerging intravitreal therapies for patients with Geographic Atrophy (GA) is currently unknown. This study therefore aimed to investigate the extent to which regular intravitreal injections may be acceptable to GA patients.<br><br>SUBJECTS/METHODS: Thirty UK-based individuals with GA secondary to age-related macular degeneration (AMD), recruited from two London-based hospitals, were interviewed in April-October 2021 regarding acceptability of new GA treatments. Participants responded to a structured questionnaire, as well as open-ended questions in a semi-structured interview.&#xa0;The Theoretical Framework of Acceptability (TFA) informed framework&#xa0;analysis of the qualitative data.<br><br>RESULTS: Twenty participants (67%) were female, and median (interquartile range (IQR)) age was 83 (78, 87) years. 37% of participants had foveal centre-involving GA, and better eye median (IQR) logMAR visual acuity was 0.30 (0.17, 0.58). Data suggested that 18 participants (60% (95% CI: 41-79%)) would accept the treatment, despite awareness of potential drawbacks. Eight participants (27% (95% CI: 10-43%) were ambivalent or undecided about treatment, and four (13%) (95% CI: 0-26%) would be unlikely to accept treatment. Reducing the frequency of injections from monthly to every other month increased the proportion of participants who considered the treatments acceptable. Conversely, factors limiting acceptability clustered around: the limited magnitude of treatment efficacy; concerns about side effects or the increased risk of neovascular AMD; and the logistical burden of regular clinic visits for intravitreal injections. Misunderstandings of potential benefits indicate the need for appropriately-designed patient education tools to support decision-making.<br><br>CONCLUSIONS: Our study suggests a majority of participants would be positive about intravitreal treatment for GA, in spite of potential burdens.},
}
@article {pmid37170011,
year = {2023},
author = {Reiter, GS and Bogunovic, H and Schlanitz, F and Vogl, WD and Seeböck, P and Ramazanova, D and Schmidt-Erfurth, U},
title = {Point-to-point associations of drusen and hyperreflective foci volumes with retinal sensitivity in non-exudative age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {37},
number = {17},
pages = {3582-3588},
pmid = {37170011},
issn = {1476-5454},
mesh = {Humans ; Aged ; Aged, 80 and over ; Retina/diagnostic imaging ; *Macular Degeneration ; Algorithms ; Tomography, Optical Coherence/methods ; Japan ; *Retinal Drusen ; },
abstract = {OBJECTIVES: To evaluate the quantitative impact of drusen and hyperreflective foci (HRF) volumes on mesopic retinal sensitivity in non-exudative age-related macular degeneration (AMD).<br><br>METHODS: In a standardized follow-up scheme of every three months, retinal sensitivity of patients with early or intermediate AMD was assessed by microperimetry using a custom pattern of 45 stimuli (Nidek MP-3, Gamagori, Japan). Eyes were consecutively scanned using Spectralis SD-OCT (20&#xb0;&#x2009;&#xd7;&#x2009;20&#xb0;, 1024&#x2009;&#xd7;&#x2009;97&#x2009;&#xd7;&#x2009;496). Fundus photographs obtained by the MP-3 allowed to map the stimuli locations onto the corresponding OCT scans. The volume and mean thickness of drusen and HRF within a circle of 240&#x2009;&#xb5;m centred at each stimulus point was determined using automated AI-based image segmentation algorithms.<br><br>RESULTS: 8055 individual stimuli from 179 visits from 51 eyes of 35 consecutive patients were matched with the respective OCT images in a point-to-point manner. The patients mean age was 76.85&#x2009;&#xb1;&#x2009;6.6 years. Mean retinal sensitivity at baseline was 25.7&#x2009;dB. 73.47% of all MP-spots covered drusen area and 2.02% of MP-spots covered HRF. A negative association between retinal sensitivity and the volume of underlying drusen (p&#x2009;<&#x2009;0.001, Estimate -0.991 db/&#xb5;m[3]) and HRF volume (p&#x2009;=&#x2009;0.002, Estimate -5.230 db/&#xb5;m[3]) was found. During observation time, no eye showed conversion to advanced AMD.<br><br>CONCLUSION: A direct correlation between drusen and lower sensitivity of the overlying photoreceptors can be observed. For HRF, a small but significant correlation was shown, which is compromised by their small size. Biomarker quantification using AI-methods allows to determine the impact of sub-clinical features in the progression of AMD.},
}
@article {pmid37169170,
year = {2023},
author = {Dikmetas, O and Gungor, G and Kapucu, Y and Kocabeyoglu, S and Kadayıfcılar, S and Eldem, B and Karahan, S and Cankaya, AB},
title = {Short-term effect of macular edema on the peripapillary retinal nerve fiber layer in patients with wet age-related macular degeneration and diabetic macular edema: A comparative study.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {42},
number = {},
pages = {103602},
doi = {10.1016/j.pdpdt.2023.103602},
pmid = {37169170},
issn = {1873-1597},
mesh = {Humans ; Aged ; *Macular Edema/drug therapy ; *Diabetic Retinopathy/complications/drug therapy ; Cross-Sectional Studies ; Retinal Ganglion Cells ; *Photochemotherapy/methods ; Photosensitizing Agents ; *Glaucoma/complications ; Tomography, Optical Coherence/methods ; Nerve Fibers ; *Diabetes Mellitus ; },
abstract = {BACKGROUND: The combined presence of glaucoma and age-related macular degeneration (ARMD), or glaucoma and diabetes mellitus (DM), occur fairly frequently, especially in elderly patients. This study was intended to compare the effect of resolving macular edema due to DM and wet ARMD on peripapillary retinal nerve fiber layer (RNFL) thickness.<br><br>METHODS: This cross-sectional study included 76 patients with macular edema secondary to DM (n&#xa0;=&#xa0;40, 52.6%) or wet ARMD (n&#xa0;=&#xa0;36, 47.4%). The control group was comprised of 34 age and sex-matched healthy subjects. All study participants underwent evaluation of central macular thickness (CMT) and the peripapillary RNFL using spectral domain-optical coherence tomography (SD-OCT). Data from eyes that received an anti-VEGF injection were obtained one month after the procedure and were compared with pre-injection data.<br><br>RESULTS: The average initial thickness of the global peripapillary RNFL was 98.9&#xa0;&#xb1;&#xa0;16.7 (61-163) &#xb5;m in the macular edema group and 92.0&#xa0;&#xb1;&#xa0;16.0 (84-115) &#xb5;m in the control group (p&#xa0;=&#xa0;0.045). The post-injection global peripapillary RNFL thickness was 97.3&#xa0;&#xb1;&#xa0;19.0 (61-163) &#xb5;m in the macular edema group and 92.2&#xa0;&#xb1;&#xa0;18.0 (81-126) &#xb5;m in the control group (p&#xa0;=&#xa0;0.187). In the DM group, the changes in global RNFL thickness, as well as central and temporal quadrant thicknesses, were found to correlate significantly with the change in CMT (r&#xa0;=&#xa0;0.356, p&#xa0;=&#xa0;0.024; r&#xa0;=&#xa0;0.545, p&#xa0;<&#xa0;0.001, respectively).<br><br>CONCLUSIONS: Macular edema in wet ARMD appeared not to affect RNFL thickness. Differences in the etiology of macular edema can have varied effects on peripapillary RNFL. It is recommended that peripapillary RNFL thickness be evaluated cautiously in DM patients receiving intravitreal anti-VEGF therapy.},
}
@article {pmid37169078,
year = {2023},
author = {Coulibaly, LM and Reiter, GS and Fuchs, P and Lachinov, D and Leingang, O and Vogl, WD and Bogunovic, H and Schmidt-Erfurth, U},
title = {Progression Dynamics of Early versus Later Stage Atrophic Lesions in Nonneovascular Age-Related Macular Degeneration Using Quantitative OCT Biomarker Segmentation.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {9},
pages = {762-770},
doi = {10.1016/j.oret.2023.05.004},
pmid = {37169078},
issn = {2468-6530},
mesh = {Humans ; *Geographic Atrophy/complications ; Retrospective Studies ; Artificial Intelligence ; Tomography, Optical Coherence/methods ; Disease Progression ; Retinal Pigment Epithelium/pathology ; *Macular Degeneration/complications ; Biomarkers ; Atrophy ; },
abstract = {PURPOSE: To investigate the progression of geographic atrophy secondary to nonneovascular age-related macular degeneration in early and later stage lesions using artificial intelligence-based precision tools.<br><br>DESIGN: Retrospective analysis of an observational cohort study.<br><br>SUBJECTS: Seventy-four eyes of 49 patients with &#x2265; 1 complete retinal pigment epithelial and outer retinal atrophy (cRORA) lesion secondary to age-related macular degeneration were included. Patients were divided between recently developed cRORA and lesions with advanced disease status.<br><br>METHODS: Patients were prospectively imaged by spectral-domain OCT volume scans. The study period encompassed 18 months with scheduled visits every 6 months. Growth rates of recent cRORA-converted lesions were compared with lesions in an advanced disease status using mixed effect models.<br><br>MAIN OUTCOME MEASURES: The progression of retinal pigment epithelial loss (RPEL) was considered the primary end point. Secondary end points consisted of external limiting membrane disruption and ellipsoid zone loss. These pathognomonic imaging biomarkers were quantified using validated deep-learning algorithms. Further, the ellipsoid zone/RPEL ratio was analyzed in both study cohorts.<br><br>RESULTS: Mean (95% confidence interval [CI]) square root progression of recently converted lesions was 79.68 (95% CI,&#xa0;-77.14 to 236.49), 68.22 (95% CI,&#xa0;-101.21 to 237.65), and 84.825 (95% CI,&#xa0;-124.82 to 294.47) mm/half year for RPEL, external limiting membrane loss, and ellipsoid zone loss respectively. Mean square root progression of advanced lesions was 131.74 (95% CI,&#xa0;-22.57 to 286.05), 129.96 (95% CI,&#xa0;-36.67 to 296.59), and 116.84 (95% CI,&#xa0;-90.56 to 324.3) mm/half year for RPEL, external limiting membrane loss, and ellipsoid zone loss, respectively. RPEL (P&#xa0;= 0.038) and external limiting membrane disruption (P&#xa0;= 0.026) progression showed significant differences between the 2 study cohorts. Further recent converters had significantly (P < 0.001) higher ellipsoid zone/RPEL ratios at all time points compared with patients in an advanced disease status (1.71 95% CI, 1.12-2.28 vs. 1.14; 95% CI, 0.56-1.71).<br><br>CONCLUSION: Early cRORA lesions have slower growth rates in comparison to atrophic lesions in advanced disease stages. Differences in growth dynamics may play a crucial role in understanding the pathophysiology of nonneovascular age-related macular degeneration and for the interpretation of clinical trials in geographic atrophy. Individual disease monitoring using artificial intelligence-based quantification paves the way toward optimized geographic atrophy management.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid37167304,
year = {2023},
author = {Periasamy, R and Patel, DD and Boye, SL and Boye, SE and Lipinski, DM},
title = {Improving retinal vascular endothelial cell tropism through rational rAAV capsid design.},
journal = {PloS one},
volume = {18},
number = {5},
pages = {e0285370},
pmid = {37167304},
issn = {1932-6203},
support = {R01 EY027767/EY/NEI NIH HHS/United States ; S10 OD030229/OD/NIH HHS/United States ; },
mesh = {Mice ; Animals ; Cattle ; Humans ; *Capsid/metabolism ; *Dependovirus/metabolism ; Endothelial Cells ; Transduction, Genetic ; Genetic Therapy ; HEK293 Cells ; Genetic Vectors/genetics ; Retina/metabolism ; Capsid Proteins/genetics/metabolism ; Tropism ; },
abstract = {Vascular endothelial cells (VEC) are essential for retinal homeostasis and their dysfunction underlies pathogenesis in diabetic retinopathy (DR) and exudative age-related macular degeneration (AMD). Studies have shown that recombinant adeno-associated virus (rAAV) vectors are effective at delivering new genetic material to neural and glial cells within the retina, but targeting VECs remains challenging. To overcome this limitation, herein we developed rAAV capsid mutant vectors with improved tropism towards retinal VEC. rAAV2/2, 2/2[QuadYF-TV], and rAAV2/9 serotype vectors (n = 9, capsid mutants per serotype) expressing GFP were generated by inserting heptameric peptides (7AA) designed to increase endothelial targeting at positions 588 (2/2 and 2/2[QuadYF-TV] or 589 (2/9) of the virus protein (VP 1-3). The packaging and transduction efficiency of the vectors were assessed in HEK293T and bovine VECs using Fluorescence microscopy and flow cytometry, leading to the identification of one mutant, termed EC5, that showed improved endothelial tropism when inserted into all three capsid serotypes. Intra-ocular and intravenous administration of EC5 mutants in C57Bl/6j mice demonstrated moderately improved transduction of the retinal vasculature, particularly surrounding the optic nerve head, and evidence of sinusoidal endothelial cell transduction in the liver. Most notably, intravenous administration of the rAAV2/2[QuadYF-TV] EC5 mutant led to a dramatic and unexpected increase in cardiac muscle transduction.},
}
@article {pmid37166519,
year = {2023},
author = {Inoda, S and Takahashi, H and Arai, Y and Tampo, H and Matsui, Y and Kawashima, H and Yanagi, Y},
title = {An AI model to estimate visual acuity based solely on cross-sectional OCT imaging of various diseases.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {10},
pages = {2775-2785},
pmid = {37166519},
issn = {1435-702X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Artificial Intelligence ; Cross-Sectional Studies ; Visual Acuity ; },
abstract = {PURPOSE: To develop an artificial intelligence (AI) model for estimating best-corrected visual acuity (BCVA) using horizontal and vertical optical coherence tomography (OCT) scans of various retinal diseases and examine factors associated with its accuracy.<br><br>METHODS: OCT images and associated BCVA measurements from 2,700 OCT images (accrued from 2004 to 2018 with an Atlantis, Triton; Topcon, Tokyo, Japan) of 756 eyes of 469 patients and their BCVA were retrospectively analysed. For each eye, one horizontal and one vertical OCT scan in cross-line mode were used. The GoogLeNet architecture was implemented. The coefficient of determination (R[2]), root mean square error (RMSE) and mean absolute error (MAE) were computed to evaluate the performance of the trained network.<br><br>RESULTS: R[2], RMSE, and MAE were 0.512, 0.350, and 0.321, respectively. R[2] was higher in phakic eyes than in pseudophakic eyes. Multivariable regression analysis showed that a higher R[2] was significantly associated with better BCVA (p&#x2009;<&#x2009;0.001) and a higher standard deviation of BCVA (p&#x2009;<&#x2009;0.001). However, the performance was worse in an external validation, with R[2] of 0.19. R[2] values for retinal vein occlusion and age-related macular degeneration were 0.961 and 0.373 in the internal validation but 0.20 and 0.22 in the external validation.<br><br>CONCLUSION: Although underspecification appears to be a fundamental problem to be addressed in AI models for predicting visual acuity, the present results suggest that AI models might have potential for estimating BCVA from OCT in AMD and RVO. Further research is needed to improve the utility of BCVA estimation for these diseases.},
}
@article {pmid37166075,
year = {2023},
author = {Hu, B and Ma, JX and Duerfeldt, AS},
title = {The cGAS-STING pathway in diabetic retinopathy and age-related macular degeneration.},
journal = {Future medicinal chemistry},
volume = {15},
number = {8},
pages = {717-729},
pmid = {37166075},
issn = {1756-8927},
support = {R01 EY019309/EY/NEI NIH HHS/United States ; R01 EY030472/EY/NEI NIH HHS/United States ; R01 EY033330/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Diabetic Retinopathy/drug therapy ; Prospective Studies ; Nucleotidyltransferases/metabolism ; *Macular Degeneration/drug therapy ; Inflammation/metabolism ; *Retinal Diseases ; *Diabetes Mellitus ; },
abstract = {Diabetic retinopathy and age-related macular degeneration are common retinal diseases with shared pathophysiology, including oxidative stress-induced inflammation. Cellular mechanisms responsible for converting oxidative stress into retinal damage are ill-defined but have begun to clarify. One common outcome of retinal oxidative stress is mitochondrial damage and subsequent release of mitochondrial DNA into the cytosol. This leads to activation of the cGAS-STING pathway, resulting in interferon release and disease-amplifying inflammation. This review summarizes the evolving link between aberrant cGAS-STING signaling and inflammation in common retinal diseases and provides prospective for targeting this system in diabetic retinopathy and age-related macular degeneration. Further defining the roles of this system in the retina is expected to reveal new disease pathology and novel therapeutic approaches.},
}
@article {pmid37165500,
year = {2024},
author = {Ponnusamy, C and Ayarivan, P and Selvamuthu, P and Natesan, S},
title = {Age-Related Macular Degeneration - Therapies and Their Delivery.},
journal = {Current drug delivery},
volume = {21},
number = {5},
pages = {683-696},
doi = {10.2174/1567201820666230510100742},
pmid = {37165500},
issn = {1875-5704},
mesh = {Humans ; Middle Aged ; Aged ; *Photochemotherapy ; Combined Modality Therapy ; *Macular Degeneration/drug therapy/complications ; },
abstract = {Age-related macular degeneration (ARMD) is a degenerative ocular disease that is the most important cause of irreversible vision loss in old-aged people in developed countries. Around fifty percent of vision impairments in developed countries are due to ARMD. It is a multifaceted disease that is associated with both genetic and environmental risk factors. The most important treatments option for ARMD includes laser photocoagulation, photodynamic therapy (PDT), Anti-VEGF Injections, and combination therapies. In this review, we also propose that topical ocular drug delivery with nanocarriers has more attention for the treatment of ARMD. The nanocarriers were specially designed for enhanced corneal residential time, prolonged drug release and action, and minimizing the frequency of administrations. Different types of nanocarriers were developed for the topical ocular delivery system, such as nanomicelles, nanoemulsions, nanosuspensions, liposomes, and polymeric nanoparticles. These topical ocular nanocarriers were administered topically, and they can fix the hydrophobic substances, increase solubility and improve the bioavailability of an administered drug. Hence the topical ocular delivery systems with nanocarriers provide a safe and effective therapeutic strategy and promising tool for the treatment of posterior segment ocular diseases ARMD.},
}
@article {pmid37164692,
year = {2023},
author = {Mori, Y and Yamamoto, A and Nakagawa, A and Hikima, T and Isowaki, A},
title = {Potential of TAK-593 Ophthalmic Emulsion for the Treatment of Age-Related Macular Degeneration.},
journal = {Biological &amp; pharmaceutical bulletin},
volume = {46},
number = {7},
pages = {921-928},
doi = {10.1248/bpb.b23-00066},
pmid = {37164692},
issn = {1347-5215},
mesh = {Humans ; *Vascular Endothelial Growth Factor A ; Emulsions/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factors ; Intravitreal Injections ; Ophthalmic Solutions ; },
abstract = {Intravitreal injection therapy of anti-vascular endothelial growth factor (VEGF) antibody or steroids is the mainstream for patients with age-related macular degeneration (AMD). However, since intravitreal injection is invasive administration, side effects such as endophthalmitis are major problems. In this study, we selected eye drops as a non-invasive treatment method, and aimed to develop eye drops that can deliver TAK-593 (VEGF receptor tyrosine kinase inhibitor) to the posterior segment of the eye. Since TAK-593 is a poorly water-soluble drug, the TAK-593 emulsion was formulated. The solubility of TAK-593 in various oils was measured, and the oil used for the emulsion was selected. Furthermore, viscosity enhancers were added to the emulsion in order to improve the drug delivery into the eye. As viscosity enhancer, xanthan gum was selected based on the properties and the viscosity of the emulsion. The delivery of TAK-593 to the posterior eye was increased by the formulation concentration and the addition of viscosity enhancers. In the laser-induced choroidal neovascularization model, TAK-593 emulsion eye drops showed the same angiogenesis-suppression efficacy as anti-VEGF antibody intravitreal injection. From these results, it was revealed that TAK-593 with an effective drug concentration can be delivered to the posterior eye by non-invasive eye drop administration.},
}
@article {pmid37164395,
year = {2023},
author = {Karmy, BE and Castro, DG and Ambresin, A},
title = {Preventive Inflammation Management with Steroids before Retreatment with Anti-VEGF after Severe Inflammation due to Brolucizumab.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {240},
number = {4},
pages = {556-562},
doi = {10.1055/a-2045-7844},
pmid = {37164395},
issn = {1439-3999},
mesh = {Humans ; Male ; Female ; Aged, 80 and over ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors ; *Wet Macular Degeneration/diagnosis/drug therapy/prevention &amp; control ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Inflammation ; *Uveitis/drug therapy ; Retreatment ; Prednisolone/therapeutic use ; Steroids/therapeutic use ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {PURPOSE: We report two successful cases of treatment by steroids after severe inflammation due to an intravitreal injection (IVI) of brolucizumab and their retreatment with another type of anti-vascular endothelial growth factor (VEGF), with steroid treatments to prevent severe inflammatory recurrence in patients with exudative age-related macular degeneration (AMD). CLINICAL CASES, CASE 1: An 88-year-old woman with exudative AMD in her left eye who had persistent subretinal fluid despite receiving an IVI, including ranibizumab and, subsequently, aflibercept. A switch to brolucizumab was decided. Two weeks after the third dose, she had a visual loss decreasing from 20/40 to counting fingers at 50 cm. Fundus examination revealed retinal whitening and perivenous sheathing. Fluoresceine angiography confirmed retinal arterial occlusion. Differential diagnoses were ruled out. She was treated with intravenous methylprednisolone and prednisolone eye drops. Three months after the treatment, visual acuity improved to 20/80 with no intraocular inflammation but subretinal fluid recurred. IVI of ranibizumab was rescheduled with preventive treatment by oral and local prednisolone without any inflammation recurrence. CASE 2: An 80-year-old man with exudative AMD in his right eye who had persistent subretinal fluid despite an IVI of aflibercept. Switching him to brolucizumab was decided. Two months after the third dose, he had blurred vision with no pain. Visual acuity decreased from 20/20 to 20/25. Examination showed 1+ anterior chamber cells and hyalitis. We confirmed the diagnosis of anterior uveitis with hyalitis. Differential diagnoses were ruled out. Treatment by prednisolone eye drops was initiated every 30 minutes for 1 day with a gradual decrease for 6 weeks. One week later, visual acuity improved to 20/20 with no inflammation. Three weeks later, subretinal fluid due to AMD increased. The patient was retreated by aflibercept with prednisolone eye drops, 48 hours before and after the IVI, with no recurrence of inflammation.<br><br>DISCUSSION: Brolucizumab is one of the latest FDA-approved anti-VEGF agents for wet AMD. Since its wider use, few cases of severe ocular inflammation have been reported in post-marketing analysis. Because wet AMD recurrences should be expected after intraocular inflammation, insight is needed into treatment tolerance in cases that received further IVI retreatment.<br><br>CONCLUSION: Our cases demonstrate that an IVI reinjection with a different anti-VEGF drug for exudative AMD recurrence can be safely reperformed. The use of local steroids could be effective in preventing recurrence of ocular inflammation after severe intraocular inflammation due to brolucizumab.},
}
@article {pmid37162855,
year = {2023},
author = {Monavarfeshani, A and Yan, W and Pappas, C and Odenigbo, KA and He, Z and Segrè, AV and van Zyl, T and Hageman, GS and Sanes, JR},
title = {Transcriptomic Analysis of the Ocular Posterior Segment Completes a Cell Atlas of the Human Eye.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37162855},
issn = {2692-8205},
support = {K99 EY033457/EY/NEI NIH HHS/United States ; K12 EY016335/EY/NEI NIH HHS/United States ; F32 EY031930/EY/NEI NIH HHS/United States ; U01 MH105960/MH/NIMH NIH HHS/United States ; R21 EY028633/EY/NEI NIH HHS/United States ; T32 NS007473/NS/NINDS NIH HHS/United States ; R01 EY031424/EY/NEI NIH HHS/United States ; },
abstract = {Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here we used high-throughput single nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in the extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases - for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ∼151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the new data complete a "Version 1" cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.},
}
@article {pmid37162702,
year = {2023},
author = {Rouvas, A and Bouratzis, N and Georgalas, I and Gouliopoulos, N},
title = {Is there any association between the frequency of wet age-related macular degeneration recurrences and the seasons of the year?.},
journal = {International ophthalmology},
volume = {43},
number = {9},
pages = {3287-3295},
pmid = {37162702},
issn = {1573-2630},
mesh = {Male ; Humans ; Aged ; Aged, 80 and over ; Female ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Seasons ; Follow-Up Studies ; Recurrence ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; Intravitreal Injections ; Tomography, Optical Coherence/methods ; Ranibizumab ; },
abstract = {PURPOSE: To investigate whether a seasonal distribution of the frequency of exudative age-related macular degeneration (wet AMD) recurrences exists.<br><br>METHODS: In total, 129 eyes with 171 recurrences in patients suffering from wet AMD were included in the study. All the patients had been treated with intravitreal anti-VEGF injections according to Pro Re Nata treatment regimen. Recurrence was defined as the re-detection of sub-retinal fluid, intraretinal fluid, and/or sub-macular hemorrhage in optical coherence tomography scans, after at least two consecutive monthly examinations with a "dry" macula. The year was divided in three 4-month periods (zone A: June-September, zone B: October-January, and zone C: February-May) based on the weather conditions prevailing in each period. Mean temperature and hours of sunlight exposure were the main weather markers recorded.<br><br>RESULTS: Eighty-two recurrences (48%) occurred during the period June-September, 50 (29.2%) during the period October-January, and 39 (22.8%) during the period February-May (Chi-square&#x2009;=&#x2009;17.5, p&#x2009;<&#x2009;0.001). Among the groups, neither patients' age (78&#x2009;&#xb1;&#x2009;8&#xa0;years A, 76&#x2009;&#xb1;&#x2009;7&#xa0;years B, and 79&#x2009;&#xb1;&#x2009;8&#xa0;years C, p&#x2009;=&#x2009;0.15) nor gender status (40% men A, 36% men B, and 51% men C, p&#x2009;=&#x2009;0.35) differed significantly. Mean temperature was 27.6&#x2009;&#xb1;&#x2009;1.8&#xa0;&#xb0;C, 15.1&#x2009;&#xb1;&#x2009;4.6&#xa0;&#xb0;C, and 16.5&#x2009;&#xb1;&#x2009;4.4&#xa0;&#xb0;C in zones A, B, and C, respectively. Hours (h) of sunlight exposure (average hours/month) were 344&#x2009;&#xb1;&#x2009;34&#xa0;h, 188&#x2009;&#xb1;&#x2009;42&#xa0;h, and 223&#x2009;&#xb1;&#x2009;57&#xa0;h in zones A, B, and C.<br><br>CONCLUSION: We demonstrated that the frequency of wet AMD recurrences is significantly elevated during the warmer months, possibly due to the higher levels of UV radiation and mean temperature. Further research is necessary to validate our findings.},
}
@article {pmid37160502,
year = {2023},
author = {Korb, CA and Lackner, KJ and Wolters, D and Schuster, AK and Nickels, S and Beutgen, VM and Münzel, T and Wild, PS and Beutel, ME and Schmidtmann, I and Pfeiffer, N and Grus, FH},
title = {Association of autoantibody levels with different stages of age-related macular degeneration (AMD): Results from the population-based Gutenberg Health Study (GHS).},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {10},
pages = {2763-2773},
pmid = {37160502},
issn = {1435-702X},
support = {AZ 961-386261/733//Stiftung Rheinland-Pfalz f&#xfc;r Innovation/ ; BMBF 01EO1503//Bundesministerium f&#xfc;r Bildung und Forschung/ ; },
mesh = {Humans ; Adult ; Middle Aged ; Aged ; *Macular Degeneration/diagnosis ; Retina ; *Retinal Drusen ; Fundus Oculi ; Autoantibodies ; },
abstract = {PURPOSE: Anti-retinal autoantibodies are assumed to be associated with age-related macular degeneration (AMD). To our knowledge, this is the first evaluation of autoantibodies in human sera of participants with different stages of AMD in a large population-based, observational cohort study in Germany.<br><br>METHODS: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany, including 15,010 participants aged between 35 and 74. Amongst others, non-mydriatic fundus photography (Visucam PRO NM&#x2122;, Carl Zeiss Meditec AG, Jena, Germany) was performed. Fundus images of the first 5000 participants were graded based on the Rotterdam Eye Study classification. Sera of participants with AMD (n=541) and sera of age-matched participants without AMD (n=490) were analyzed by antigen-microarrays. Besides descriptive statistics, autoantibody-levels were compared by Mann-Whitney-U test and the associations of level of autoantibodies with AMD were calculated by logistic regression analysis. Likewise, possible associations of the autoantibodies and both clinical and laboratory parameters on AMD subjects were analyzed.<br><br>RESULTS: Autoantibodies against transferrin (p<0.001) were significantly downregulated in participants with early AMD and soft, distinct drusen (&#x2265;63 &#x3bc;m) or pigmentary abnormalities only compared to Controls. Mitogen-activated protein kinase 3 (p=0.041), glutathione peroxidase 4 (p=0.048), clusterin (p=0.045), lysozyme (p=0.19), protein kinase C substrate 80K-H (p=0.02), heat shock 70 kDa protein 1A (p=0.04) and insulin (p=0.018) show a trend between Control and participants with early AMD and soft, distinct drusen (&#x2265;63 &#x3bc;m) or pigmentary abnormalities only.<br><br>CONCLUSIONS: This study contributes to a growing knowledge of autoantibodies in association with different AMD stages compared to controls in the context of a large population-based study in Germany. Especially autoantibodies against inflammatory proteins were downregulated in participants with early AMD and soft, distinct drusen (&#x2265;63 &#x3bc;m) or pigmentary abnormalities only.},
}
@article {pmid37160501,
year = {2023},
author = {Daich Varela, M and Sen, S and De Guimaraes, TAC and Kabiri, N and Pontikos, N and Balaskas, K and Michaelides, M},
title = {Artificial intelligence in retinal disease: clinical application, challenges, and future directions.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {11},
pages = {3283-3297},
pmid = {37160501},
issn = {1435-702X},
support = {/WT_/Wellcome Trust/United Kingdom ; 099173/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Child ; Infant, Newborn ; Humans ; Aged ; Artificial Intelligence ; *Retinal Diseases/diagnosis/therapy ; Algorithms ; Retina ; *Diabetic Retinopathy/diagnosis ; *Macular Degeneration/diagnosis ; },
abstract = {Retinal diseases are a leading cause of blindness in developed countries, accounting for the largest share of visually impaired children, working-age adults (inherited retinal disease), and elderly individuals (age-related macular degeneration). These conditions need specialised clinicians to interpret multimodal retinal imaging, with diagnosis and intervention potentially delayed. With an increasing and ageing population, this is becoming a global health priority. One solution is the development of artificial intelligence (AI) software to facilitate rapid data processing. Herein, we review research offering decision support for the diagnosis, classification, monitoring, and treatment of retinal disease using AI. We have prioritised diabetic retinopathy, age-related macular degeneration, inherited retinal disease, and retinopathy of prematurity. There is cautious optimism that these algorithms will be integrated into routine clinical practice to facilitate access to vision-saving treatments, improve efficiency of healthcare systems, and assist clinicians in processing the ever-increasing volume of multimodal data, thereby also liberating time for doctor-patient interaction and co-development of personalised management plans.},
}
@article {pmid37156326,
year = {2023},
author = {Xiao, J and Zhang, JY and Luo, W and He, PC and Skondra, D},
title = {The Emerging Role of Gut Microbiota in Age-Related Macular Degeneration.},
journal = {The American journal of pathology},
volume = {193},
number = {11},
pages = {1627-1637},
doi = {10.1016/j.ajpath.2023.04.006},
pmid = {37156326},
issn = {1525-2191},
abstract = {Age-related macular degeneration (AMD) is a progressive, degenerative retinal disease that is a leading cause of blindness globally. Although multiple risk factors have been identified regarding disease incidence and progression, including smoking, genetics, and diet, the understanding of AMD pathogenesis remains unclear. As such, primary prevention is lacking, and current treatments have limited efficacy. More recently, the gut microbiome has emerged as an influential player in various ocular pathologies. As mediators of metabolism and immune regulation, perturbations in gut microbiota may impart significant effects distally on the neuroretina and its adjacent tissues, termed the gut-retina axis. In this review, key studies over the past several decades are summarized, both in humans and in animal models, which shed insight on the relationships between the gut microbiome and retinal biology and their implications for AMD. The literature linking gut dysbiosis with AMD is examined, along with preclinical animal models and techniques apt for studying the role of gut microbiota in AMD pathogenesis, which include interactions with systemic inflammation, immune regulation, chorioretinal gene expression, and diet. As understanding of the gut-retina axis continues to advance, so too will the possibility for more accessible and effective prevention and therapy of this vision-threatening condition.},
}
@article {pmid37155967,
year = {2023},
author = {Zola, M and Bousquet, E and Favard, C and Gigon, A and Mantel, I and Behar-Cohen, F},
title = {INDOCYANINE GREEN ANGIOGRAPHY OF TYPE 1 MACULAR NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION AND CENTRAL SEROUS CHORIORETINOPATHY REVEALS DIFFERENT DISEASE MECHANISMS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {8},
pages = {1255-1263},
doi = {10.1097/IAE.0000000000003833},
pmid = {37155967},
issn = {1539-2864},
mesh = {Humans ; Male ; Female ; *Central Serous Chorioretinopathy/complications/diagnosis ; Indocyanine Green ; Fluorescein Angiography/methods ; Endothelial Growth Factors ; Retrospective Studies ; *Macular Degeneration ; *Choroidal Neovascularization/diagnosis/drug therapy ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: To assess the rate of late phase hyperfluorescent plaque (LPHP) in Type 1 macular neovascularization (MNV) in central serous chorioretinopathy (CSCR) and age-related macular degeneration (AMD) and to evaluate its prognostic value.<br><br>METHODS: Retrospective study including Type 1 MNV in AMD and CSCR, from 2012 to 2020. Eyes with a late indocyanine green angiography image (>20 minutes) and clear visualization of MNV on optical coherence tomography angiography (OCTA) were included. Quantitative and qualitative parameters on optical coherence tomography and best-corrected visual acuity were recorded at baseline and after three monthly antivascular endothelial growth factor injections.<br><br>RESULTS: Eighty-three eyes were included, 35 with CSCR and 48 with AMD. Patients in the CSCR group were significantly younger than in the AMD group (61.3 &#xb1; 10.4 vs. 80.2 &#xb1; 6.8 years, respectively, P < 0.001), predominantly male (68.6% CSCR vs. 35.4% AMD; P = 0.003), and with a thicker choroid (379 &#xb1; 93.3 &#xb5; m vs. 204.2 &#xb1; 93.2 &#xb5; m; P < 0.001). Type 1 MNV in CSCR showed fewer LPHP compared with AMD (31.4% vs. 77.1%; P < 0.001). The baseline visual acuity was lower in patients with LPHP (0.37 &#xb1; 0.22 vs. 0.27 &#xb1; 0.28 logarithm of the minimum angle of resolution, P = 0.03). On multivariate analysis, AMD was associated with the presence of LPHP (P < 0.001). No significant difference in the response to antivascular endothelial growth factor was observed.<br><br>CONCLUSION: Leakage of macromolecules from MNV and accumulation in the retinal pigment epithelium and/or in the stroma imaged by the LPHP is less common in eyes with Type 1 MNV in CSCR than in AMD. Late phase indocyanine green angiography imaging offers an insight into the metabolism of the dye and the environment surrounding the neovascular membrane.},
}
@article {pmid37155898,
year = {2023},
author = {Lyu, Y and Tschulakow, AV and Wang, K and Brash, DE and Schraermeyer, U},
title = {Chemiexcitation and melanin in photoreceptor disc turnover and prevention of macular degeneration.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {20},
pages = {e2216935120},
pmid = {37155898},
issn = {1091-6490},
support = {R01 AR070851/AR/NIAMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; },
mesh = {Mice ; Animals ; *Melanins/metabolism ; Lipofuscin/metabolism ; *Macular Degeneration/prevention &amp; control/pathology ; Retina/metabolism ; Retinal Pigment Epithelium/metabolism ; ATP-Binding Cassette Transporters ; },
abstract = {Age-related macular degeneration, Stargardt disease, and their Abca4[-/-] mouse model are characterized by accelerated accumulation of the pigment lipofuscin, derived from photoreceptor disc turnover in the retinal pigment epithelium (RPE); lipofuscin accumulation and retinal degeneration both occur earlier in albino mice. Intravitreal injection of superoxide (O2[•-]) generators reverses lipofuscin accumulation and rescues retinal pathology, but neither the target nor mechanism is known. Here we show that RPE contains thin multi-lamellar membranes (TLMs) resembling photoreceptor discs, which associate with melanolipofuscin granules in pigmented mice but in albinos are 10-fold more abundant and reside in vacuoles. Genetically over-expressing tyrosinase in albinos generates melanosomes and decreases TLM-related lipofuscin. Intravitreal injection of generators of O2[•-] or nitric oxide ([•]NO) decreases TLM-related lipofuscin in melanolipofuscin granules of pigmented mice by ~50% in 2 d, but not in albinos. Prompted by evidence that O2[•-] plus [•]NO creates a dioxetane on melanin that excites its electrons to a high-energy state (termed "chemiexcitation"), we show that exciting electrons directly using a synthetic dioxetane reverses TLM-related lipofuscin even in albinos; quenching the excited-electron energy blocks this reversal. Melanin chemiexcitation assists in safe photoreceptor disc turnover.},
}
@article {pmid37154984,
year = {2023},
author = {Mori, R and Honda, S and Gomi, F and Tsujikawa, A and Koizumi, H and Ochi, H and Ohsawa, S and Okada, AA and , },
title = {Correction to: Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 1-year results from the Japan subgroup of the phase 3 TENAYA trial.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {3},
pages = {311},
doi = {10.1007/s10384-023-00996-7},
pmid = {37154984},
issn = {1613-2246},
}
@article {pmid37153596,
year = {2023},
author = {Duncan, RS and Keightley, A and Lopez, AA and Hall, CW and Koulen, P},
title = {Proteome changes in a human retinal pigment epithelial cell line during oxidative stress and following antioxidant treatment.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1138519},
pmid = {37153596},
issn = {1664-3224},
support = {R01 EY030747/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Antioxidants/pharmacology/metabolism ; Proteome/metabolism ; Oxidative Stress/physiology ; Tocopherols/metabolism ; *Macular Degeneration/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Age related macular degeneration (AMD) is the most common cause of blindness in the elderly. Oxidative stress contributes to retinal pigment epithelium (RPE) dysfunction and cell death thereby leading to AMD. Using improved RPE cell model systems, such as human telomerase transcriptase-overexpressing (hTERT) RPE cells (hTERT-RPE), pathophysiological changes in RPE during oxidative stress can be better understood. Using this model system, we identified changes in the expression of proteins involved in the cellular antioxidant responses after induction of oxidative stress. Some antioxidants such as vitamin E (tocopherols and tocotrienols) are powerful antioxidants that can reduce oxidative damage in cells. Alpha-tocopherol (α-Toc or αT) and gamma-tocopherol (γ-Toc or γT) are well-studied tocopherols, but signaling mechanisms underlying their respective cytoprotective properties may be distinct. Here, we determined what effect oxidative stress, induced by extracellularly applied tBHP in the presence and absence of αT and/or γT, has on the expression of antioxidant proteins and related signaling networks. Using proteomics approaches, we identified differential protein expression in cellular antioxidant response pathways during oxidative stress and after tocopherol treatment. We identified three groups of proteins based on biochemical function: glutathione metabolism/transfer, peroxidases and redox-sensitive proteins involved in cytoprotective signaling. We found that oxidative stress and tocopherol treatment resulted in unique changes in these three groups of antioxidant proteins indicate that αT and γT independently and by themselves can induce the expression of antioxidant proteins in RPE cells. These results provide novel rationales for potential therapeutic strategies to protect RPE cells from oxidative stress.},
}
@article {pmid37153444,
year = {2023},
author = {Zelinger, L and Martin, TM and Advani, J and Campello, L and English, MA and Kwong, A and Weber, C and Maykoski, J and Sergeev, YV and Fariss, R and Chew, EY and Klein, ML and Swaroop, A},
title = {Ultra-rare complement factor 8 coding variants in families with age-related macular degeneration.},
journal = {iScience},
volume = {26},
number = {4},
pages = {106417},
pmid = {37153444},
issn = {2589-0042},
support = {P30 EY010572/EY/NEI NIH HHS/United States ; R01 EY021532/EY/NEI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; ZIA EY000546/ImNIH/Intramural NIH HHS/United States ; },
abstract = {Genome-wide association studies have uncovered 52 independent common and rare variants across 34 genetic loci, which influence susceptibility to age related macular degeneration (AMD). Of the 5 AMD-associated complement genes, complement factor H (CFH) and CFI exhibit a significant rare variant burden implicating a major contribution of the complement pathway to disease pathology. However, the efforts for developing AMD therapy have been challenging as of yet. Here, we report the identification of ultra-rare variants in complement factors 8A and 8B, two components of the terminal complement membrane attack complex (MAC), by whole exome sequencing of a cohort of AMD families. The identified C8 variants impact local interactions among proteins of C8 triplex in vitro, indicating their effect on MAC stability. Our results suggest that MAC, and not the early steps of the complement pathway, might be a more effective target for designing treatments for AMD.},
}
@article {pmid37152298,
year = {2023},
author = {Wan, C and Fang, J and Hua, X and Chen, L and Zhang, S and Yang, W},
title = {Automated detection of myopic maculopathy using five-category models based on vision outlooker for visual recognition.},
journal = {Frontiers in computational neuroscience},
volume = {17},
number = {},
pages = {1169464},
pmid = {37152298},
issn = {1662-5188},
abstract = {PURPOSE: To propose a five-category model for the automatic detection of myopic macular lesions to help grassroots medical institutions conduct preliminary screening of myopic macular lesions from limited number of color fundus images.<br><br>METHODS: First, 1,750 fundus images of non-myopic retinal lesions and four categories of pathological myopic maculopathy were collected, graded, and labeled. Subsequently, three five-classification models based on Vision Outlooker for Visual Recognition (VOLO), EfficientNetV2, and ResNet50 for detecting myopic maculopathy were trained with data-augmented images, and the diagnostic results of the different trained models were compared and analyzed. The main evaluation metrics were sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), area under the curve (AUC), kappa and accuracy, and receiver operating characteristic curve (ROC).<br><br>RESULTS: The diagnostic accuracy of the VOLO-D2 model was 96.60% with a kappa value of 95.60%. All indicators used for the diagnosis of myopia-free macular degeneration were 100%. The sensitivity, NPV, specificity, and PPV for diagnosis of leopard fundus were 96.43, 98.33, 100, and 100%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of diffuse chorioretinal atrophy were 96.88, 98.59, 93.94, and 99.29%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of patchy chorioretinal atrophy were 92.31, 99.26, 97.30, and 97.81%, respectively. The sensitivity, specificity, PPV, and NPV for the diagnosis of macular atrophy were 100, 98.10, 84.21, and 100%, respectively.<br><br>CONCLUSION: The VOLO-D2 model accurately identified myopia-free macular lesions and four pathological myopia-related macular lesions with high sensitivity and specificity. It can be used in screening pathological myopic macular lesions and can help ophthalmologists and primary medical institution providers complete the initial screening diagnosis of patients.},
}
@article {pmid37150939,
year = {2024},
author = {Pece, A and Fossataro, F and Maione, G and Liuzzi, R},
title = {Structural and clinical changes in previously treated type 1 macular neovascularization in non-responder AMD eyes switched to brolucizumab.},
journal = {European journal of ophthalmology},
volume = {34},
number = {1},
pages = {245-251},
doi = {10.1177/11206721231174491},
pmid = {37150939},
issn = {1724-6016},
mesh = {Humans ; Prospective Studies ; Antibodies, Monoclonal, Humanized/therapeutic use ; Retinal Pigment Epithelium ; Tomography, Optical Coherence/methods ; *Retinal Detachment/drug therapy ; Biomarkers ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To examine structural and clinical changes in previously treated type 1 macular neovascularization (MNV) in non-responder age-related macular degeneration (nAMD) eyes switched to brolucizumab. Subretinal hyper-reflective material (SHRM), intraretinal (IRF) and subretinal fluid (SRF) presence, fibrovascular-pigment epithelium detachment (PED) height and central macular thickness (CMT) variation were analyzed using optical coherence tomography (OCT).<br><br>METHODS: In this prospective study all patients underwent a complete ophthalmological evaluation including structural OCT at baseline (T0), one month (T1), three (T2), four (T3) and six months after switching to brolucizumab treatment (T4). Non-responder criterion was the persistence of IRF and SRF. Moreover, CMT and BCVA had shown worsening or no improvement before switching to brolucizumab. Clinical function and structural activity biomarkers were measured at each visit and changes were analyzed. P value <0.05 was considered statistically significant.<br><br>RESULTS: Twenty eyes of twenty patients were enrolled. All the structural variables examined during the follow-up showed significant reductions. Decreases in IRF, SRF and PED were already significant at T1 (p&#x2009;<&#x2009;0.05). SHRM was significantly reduced at T2 (p&#x2009;<&#x2009;0.05). Structural biomarkers were absent at T3. At T4, all biomarkers remained stable while SHRM was no longer detectable in 18 patients. Changes in visual acuity from baseline to T4 were not significant.<br><br>CONCLUSION: This short-term experience highlights that brolucizumab might be considered an effective treatment option in nAMD with type 1 MNV, as it can promote a reduction of structural activity biomarkers.},
}
@article {pmid37150437,
year = {2023},
author = {Cui, B and Guo, X and Zhou, W and Zhang, X and He, K and Bai, T and Lin, D and Wei-Zhang, S and Zhao, Y and Liu, S and Zhou, H and Wang, Q and Yao, X and Shi, Y and Xie, R and Dong, X and Lei, Y and Du, M and Chang, Y and Xu, H and Zhou, D and Yu, Y and Wang, X and Yan, H},
title = {Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells.},
journal = {Metabolism: clinical and experimental},
volume = {144},
number = {},
pages = {155584},
doi = {10.1016/j.metabol.2023.155584},
pmid = {37150437},
issn = {1532-8600},
mesh = {Aged ; Humans ; Mice ; Animals ; Inflammasomes ; Vascular Endothelial Growth Factor A/genetics/metabolism/therapeutic use ; Proteomics ; *Choroidal Neovascularization/prevention &amp; control/drug therapy/etiology ; Myeloid Cells/metabolism ; *Macular Degeneration/therapy/complications/metabolism ; DNA-Binding Proteins ; },
abstract = {The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF) plays a crucial role in choroidal neovascularization (CNV), and anti-VEGF therapy is recommended as first-line therapy for nvAMD. However, many patients do not radically benefit from this therapy. Epidemiological data suggest that physical exercise is beneficial for many human diseases, including nvAMD. Yet, its protective mechanism and therapeutic potential remain unknown. Here, using clinical samples and mouse models, we found that exercise reduced CNV and enhanced anti-angiogenic therapy efficacy by inhibiting AIM2 inflammasome activation. Furthermore, transfusion of serum from exercised mice transferred the protective effects to sedentary mice. Proteomic data revealed that exercise promoted the release of adiponectin, an anti-inflammatory adipokine from adipose tissue into the circulation, which reduced ROS-mediated DNA damage and suppressed AIM2 inflammasome activation in myeloid cells of CNV eyes through AMPK-p47phox pathway. Simultaneous targeting AIM2 inflammasome product IL-1β and VEGF produced a synergistic effect for treating choroidal neovascularization. Collectively, this study highlights the therapeutic potential of an exercise-AMD axis and uncovers the AIM2 inflammasome and its product IL-1β as potential targets for treating nvAMD patients and enhancing the efficacy of anti-VEGF monotherapy.},
}
@article {pmid37149627,
year = {2023},
author = {Kuranami, A and Maruko, R and Maruko, I and Hasegawa, T and Iida, T},
title = {Pachychoroid neovasculopathy has clinical properties that differ from conventional neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {7379},
pmid = {37149627},
issn = {2045-2322},
mesh = {Aged ; Female ; Humans ; Male ; Angiogenesis Inhibitors/therapeutic use ; Choroid/blood supply ; *Choroidal Neovascularization/diagnostic imaging/drug therapy ; Fluorescein Angiography/methods ; *Macula Lutea/pathology ; *Macular Degeneration/pathology ; Neovascularization, Pathologic/pathology ; Retrospective Studies ; Tomography, Optical Coherence/methods ; },
abstract = {To determine the clinical properties of pachychoroid neovasculopathy (PNV) that differ from conventional neovascular age-related macular degeneration (nAMD) and suggest that they are different clinical entities. To accomplish this, we reviewed the medical records of 100 consecutive patients diagnosed with nAMD. All of the patients were Japanese, and their mean age was 75.5 years. There were 72 men and 28 women. For the bilateral cases, only the right eye was analyzed. An eye was diagnosed with PNV when a macular neovascularization (MNV) was detected just above the dilated choroidal vessels. The Indocyanine green angiographic (ICGA) and en face optical coherence tomographic (OCT) images were used to assess the vertical symmetry of the medium and large choroidal vessels. The subfoveal choroidal thickness (SCT) was also measured manually in the OCT images. After reclassification, there were 29 (29%) patients with typical nAMD (25 with type 1 MNV, 4 with type 2 MNV), 43 (43%) with PNV, 21 (21%) with polypoidal choroidal vasculopathy, and 7 (7%) with retinal angiomatous proliferation. Of the 43 PNV, 17 (39.5%) had polypoidal lesions and 26 (60.5%) had no polypoidal lesions. The percentage of eyes with vertical asymmetry of the medium and large choroidal vessels was significantly greater in the 35 PNV (81.4%) than in the 16 non-PNV (28.1%; P < 0.01) cases. The mean SCT was significantly thicker in the PNV eyes than in the non-PNV eyes (298 ± 96 μm vs. 228 ± 82 μm; P < 0.01). The response of PNV to anti-vascular endothelial growth factor treatments was better than that of non-PNV eyes [higher dry macula rate after the loading period (90.9% vs. 59.1%), fewer total number of injections (11.0 ± 2.9 vs. 13.4 ± 3.2), and longer treatment intervals for the anti-VEGF therapy (8.4 ± 3.1 vs. 13.4 ± 3.2 weeks) at 2 years (all P < 0.01)]. These differences in the morphology and response to anti-VEGF treatments suggest that PNV is a separate clinical entity to conventional nAMD.},
}
@article {pmid37147305,
year = {2023},
author = {Kuchroo, M and DiStasio, M and Song, E and Calapkulu, E and Zhang, L and Ige, M and Sheth, AH and Majdoubi, A and Menon, M and Tong, A and Godavarthi, A and Xing, Y and Gigante, S and Steach, H and Huang, J and Huguet, G and Narain, J and You, K and Mourgkos, G and Dhodapkar, RM and Hirn, MJ and Rieck, B and Wolf, G and Krishnaswamy, S and Hafler, BP},
title = {Single-cell analysis reveals inflammatory interactions driving macular degeneration.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {2589},
pmid = {37147305},
issn = {2041-1723},
support = {P30 EY026878/EY/NEI NIH HHS/United States ; R01 EY034234/EY/NEI NIH HHS/United States ; T35 DK104689/DK/NIDDK NIH HHS/United States ; T32 AI155387/AI/NIAID NIH HHS/United States ; K08 EY026652/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Mice ; Animals ; *Macular Degeneration/metabolism ; Retina/metabolism ; Neuroglia/metabolism ; *Neurodegenerative Diseases/metabolism ; Single-Cell Analysis ; },
abstract = {Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer's disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1β which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.},
}
@article {pmid37146693,
year = {2023},
author = {Hatamnejad, A and Patil, NS and Mihalache, A and Popovic, MM and Kertes, PJ and Muni, RH and Wong, DT},
title = {Efficacy and safety of anti-vascular endothelial growth agents for the treatment of polypoidal choroidal vasculopathy: A systematic review and meta-analysis.},
journal = {Survey of ophthalmology},
volume = {68},
number = {5},
pages = {920-928},
doi = {10.1016/j.survophthal.2023.04.002},
pmid = {37146693},
issn = {1879-3304},
mesh = {Humans ; *Ranibizumab/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Polypoidal Choroidal Vasculopathy ; Bevacizumab/therapeutic use ; Intravitreal Injections ; Observational Studies as Topic ; },
abstract = {There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence.},
}
@article {pmid37146684,
year = {2023},
author = {Hyman, MJ and Skondra, D and Aggarwal, N and Moir, J and Boucher, N and McKay, BS and MacCumber, MW and Lavine, JA},
title = {Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {9},
pages = {745-752},
pmid = {37146684},
issn = {2468-6530},
support = {K08 EY030923/EY/NEI NIH HHS/United States ; R01 EY034486/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Levodopa/therapeutic use ; *Macular Degeneration ; Retrospective Studies ; Prospective Studies ; Eye ; },
abstract = {OBJECTIVE: To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD).<br><br>DESIGN: Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1-2) and case-control analysis in the Merative MarketScan Research Databases (#3).<br><br>PARTICIPANTS: Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged &#x2265; 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3).<br><br>METHODS: Eyes were divided into 2 groups (#1-2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100-300 mg, and approximately > 300 mg per day, #3).<br><br>MAIN OUTCOME MEASURES: Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2-3) after adjusting for AMD risk factors.<br><br>RESULTS: In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N&#xa0;= 84 088 control vs. 530 L-DOPA eyes, P&#xa0;= 0.006). In eyes with nonneovascular AMD (N&#xa0;= 42 081-203 155 control vs. 314-1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P&#xa0;= 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P&#xa0;= 0.024). In the MarketScan databases (N&#xa0;= 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75-0.97) and 23% (OR, 0.77; 95% CI, 0.67-0.87), respectively.<br><br>CONCLUSIONS: Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37146512,
year = {2023},
author = {Stanhope, SC and Brandwine-Shemmer, T and Blum, HR and Doud, EH and Jannasch, A and Mosley, AL and Minke, B and Weake, VM},
title = {Proteome-wide quantitative analysis of redox cysteine availability in the Drosophila melanogaster eye reveals oxidation of phototransduction machinery during blue light exposure and age.},
journal = {Redox biology},
volume = {63},
number = {},
pages = {102723},
pmid = {37146512},
issn = {2213-2317},
support = {R01 EY024905/EY/NEI NIH HHS/United States ; R01 EY033734/EY/NEI NIH HHS/United States ; T32 GM125620/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; *Cysteine/metabolism ; *Proteome/metabolism ; Drosophila melanogaster/metabolism ; Reactive Oxygen Species/metabolism ; Oxidative Stress/physiology ; Oxidation-Reduction ; Drosophila/metabolism ; Light Signal Transduction ; Oxygen ; },
abstract = {The retina is one of the highest oxygen-consuming tissues because visual transduction and light signaling processes require large amounts of ATP. Thus, because of the high energy demand, oxygen-rich environment, and tissue transparency, the eye is susceptible to excess production of reactive oxygen species (ROS) resulting in oxidative stress. Oxidative stress in the eye is associated with the development and progression of ocular diseases including cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy. ROS can modify and damage cellular proteins, but can also be involved in redox signaling. In particular, the thiol groups of cysteines can undergo reversible or irreversible oxidative post-translational modifications (PTMs). Identifying the redox-sensitive cysteines on a proteome-wide scale provides insight into those proteins that act as redox sensors or become irreversibly damaged upon exposure to oxidative stress. In this study, we profiled the redox proteome of the Drosophila eye under prolonged, high intensity blue light exposure and age using iodoacetamide isobaric label sixplex reagents (iodo-TMT) to identify changes in cysteine availability. Although redox metabolite analysis of the major antioxidant, glutathione, revealed similar ratios of its oxidized and reduced form in aged or light-stressed eyes, we observed different changes in the redox proteome under these conditions. Both conditions resulted in significant oxidation of proteins involved in phototransduction and photoreceptor maintenance but affected distinct targets and cysteine residues. Moreover, redox changes induced by blue light exposure were accompanied by a large reduction in light sensitivity that did not arise from a reduction in the photopigment level, suggesting that the redox-sensitive cysteines we identified in the phototransduction machinery might contribute to light adaptation. Our data provide a comprehensive description of the redox proteome of Drosophila eye tissue under light stress and aging and suggest how redox signaling might contribute to light adaptation in response to acute light stress.},
}
@article {pmid37145334,
year = {2023},
author = {Boscher, C and Erol, O and Luscan, R},
title = {Remodeling of the choroidal vasculature and the role of choriocapillaris perfusion drop in pachychoroid diseases: a global rheological approach.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {10},
pages = {3045-3046},
pmid = {37145334},
issn = {1435-702X},
mesh = {Humans ; Choroid/blood supply ; *Choroid Diseases/diagnosis ; Perfusion ; Fluorescein Angiography ; Tomography, Optical Coherence ; *Central Serous Chorioretinopathy ; Retrospective Studies ; },
}
@article {pmid37144908,
year = {2023},
author = {Wei, W and Anantharanjit, R and Patel, RP and Cordeiro, MF},
title = {Detection of macular atrophy in age-related macular degeneration aided by artificial intelligence.},
journal = {Expert review of molecular diagnostics},
volume = {23},
number = {6},
pages = {485-494},
doi = {10.1080/14737159.2023.2208751},
pmid = {37144908},
issn = {1744-8352},
mesh = {Humans ; Artificial Intelligence ; Fluorescein Angiography ; *Macular Degeneration ; *Geographic Atrophy/diagnosis ; *Eye Diseases ; Atrophy ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment worldwide. The endpoint of AMD, both in its dry or wet form, is macular atrophy (MA) which is characterized by the permanent loss of the RPE and overlying photoreceptors either in dry AMD or in wet AMD. A recognized unmet need in AMD is the early detection of MA development.<br><br>AREAS COVERED: Artificial Intelligence (AI) has demonstrated great impact in detection of retinal diseases, especially with its robust ability to analyze big data afforded by ophthalmic imaging modalities, such as color fundus photography (CFP), fundus autofluorescence (FAF), near-infrared reflectance (NIR), and optical coherence tomography (OCT). Among these, OCT has been shown to have great promise in identifying early MA using the new criteria in 2018.<br><br>EXPERT OPINION: There are few studies in which AI-OCT methods have been used to identify MA; however, results are very promising when compared to other imaging modalities. In this paper, we review the development and advances of ophthalmic imaging modalities and their combination with AI technology to detect MA in AMD. In addition, we emphasize the application of AI-OCT as an objective, cost-effective tool for the early detection and monitoring of the progression of MA in AMD.},
}
@article {pmid37144369,
year = {2023},
author = {Yusef, YN and Budzinskaya, MV and Plyukhova, AA},
title = {[Prognostic factors and a customized approach to anti-VEGF therapy for exudative age-related macular degeneration. Analysis of the risk of macular atrophy development].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {3. Vyp. 2},
pages = {51-55},
doi = {10.17116/oftalma202313903251},
pmid = {37144369},
issn = {0042-465X},
mesh = {Humans ; Prognosis ; *Macular Degeneration/diagnosis/drug therapy/complications ; Choroid/pathology ; Retinal Pigment Epithelium ; Atrophy/diagnosis ; Fluorescein Angiography ; Tomography, Optical Coherence ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is a chronic progressive multifactorial disease characterized by a degenerative process in the retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris of the fovea with secondary neuroepithelial (NE) damage. Intravitreal administration of drugs that inhibit VEGF is recognized as the only treatment for exudative form of AMD. Literature data is limited, and do not allow drawing conclusions about the influence of various factors (identified using OCT in the EDI mode) on the development of various subtypes of atrophy and their progression, so we decided to conduct our own study and research the possible timing and risks of developing various subtypes of macular atrophy in patients with exudative AMD receiving anti-VEGF therapy. As a result of the study, it was revealed that general macular atrophy (p=0.005) has a predominant effect on BCVA in the first year of the follow-up, while subtypes of atrophy anatomically less pronounced at one year of the follow-up manifest themselves only in the second year of the follow-up (p<0.05). Although color photography and autofluorescence are currently the only approved methods for assessing the degree of atrophy, the use of OCT may reveal reliable precursor endpoints that will facilitate and allow earlier and more accurate assessment of neurosensory tissue loss resulting from the atrophy. Thus, the development of macular atrophy is influenced by such parameters of disease activity as intraretinal fluid (p=0.006952), RPE detachment (p=0.001530) and the type of neovascularization (p=0.028860), as well as neurodenegerative changes in the form of drusen (p=0.011259) and cysts (p=0.042023). The new classification of atrophy according to the degree and localization of the lesion allows more differentiated conclusions about the effect of anti-VEGF drugs on the development of certain types of atrophy, which can be a decisive factor in determining the treatment tactics.},
}
@article {pmid37144368,
year = {2023},
author = {Budzinskaya, MV and Plyukhova, AA and Alkharki, L},
title = {[Modern trends in anti-VEGF therapy for age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {3. Vyp. 2},
pages = {46-50},
doi = {10.17116/oftalma202313903246},
pmid = {37144368},
issn = {0042-465X},
mesh = {Humans ; Middle Aged ; Aged ; *Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor A ; Angiogenesis Inhibitors/therapeutic use ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; },
abstract = {Age-related macular degeneration (AMD) develops in people aged 50 years and older, its pathogenesis involves progressive destruction of the retinal pigment epithelium and Bruch's membrane. There are eight currently known anti-VEGF drugs for treating the neovascular form of AMD, four of them have already been registered and are used in clinical practice. The first registered drug was pegaptanib, which selectively blocks VEGF165. Subsequently, a molecule with a similar mechanism of action was developed and named ranibizumab, which is a humanized monoclonal Fab fragment; it was specifically designed for ophthalmology. Its advantage over pegaptanib was neutralization of all active VEGF-A isoforms. Aflibercept and conbercept are recombinant fusion proteins that act as soluble decoy receptors for VEGF family proteins. Phase III data from the VIEW 1 and 2 studies showed that intraocular injections (IVI) of aflibercept every 1 or 2 months for a year resulted in comparable functional outcomes to monthly IVI of ranibizumab for one year. The next molecule for anti-VEGF therapy that showed effectiveness was brolucizumab - a single-chain fragment of a humanized antibody that binds with high affinity to various VEGF-A isoforms. Simultaneously with studying brolucizumab, another study was conducted involving Abicipar pegol, but that drug showed a high rate of complications. The latest drug registered for the treatment of neovascular AMD is faricimab. The molecule of this drug is a humanized immunoglobulin G antibody that acts on two key points of angiogenesis: VEGF-A and angiopoietin-2 (Ang-2). Thus, the strategy for advancing anti-VEGF therapy lies in the development of molecules with greater efficiency (better effect on newly formed vessels leading to resorption of exudate in the retina, under the neuroepithelium and under the retinal pigment epithelium), which allows not just to preserve vision, but to also significantly improve it when there is no macular atrophy.},
}
@article {pmid37144026,
year = {2023},
author = {Stanhope, J and Weinstein, P},
title = {Will the increased use of ring lights during the coronavirus pandemic lead to a growing burden of macular degeneration?.},
journal = {Medical hypotheses},
volume = {175},
number = {},
pages = {111064},
pmid = {37144026},
issn = {1532-2777},
abstract = {The pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has brought with it many changes in the way with live, work, and socialise. One such change is an increase in the use of videoconferencing for communication with friends, family and work colleagues, and doing presentations, while physically distancing. We demonstrate an increase in the use of ring lights during the pandemic, and argue that this increased exposure to blue light may lead to a growing burden of macular degeneration in coming years.},
}
@article {pmid37142778,
year = {2023},
author = {Teo, KYC},
title = {The NOD audit: Insights into the current state of management for neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {37},
number = {17},
pages = {3521-3522},
pmid = {37142778},
issn = {1476-5454},
mesh = {Humans ; *Macular Degeneration/therapy ; *Choroidal Neovascularization/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Tomography, Optical Coherence ; },
}
@article {pmid37142441,
year = {2023},
author = {Muniyandi, A and Hartman, GD and Song, Y and Mijit, M and Kelley, MR and Corson, TW},
title = {Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.},
journal = {The Journal of pharmacology and experimental therapeutics},
volume = {386},
number = {1},
pages = {15-25},
pmid = {37142441},
issn = {1521-0103},
support = {R01 CA205166/CA/NCI NIH HHS/United States ; F31 EY035171/EY/NEI NIH HHS/United States ; R01 CA231267/CA/NCI NIH HHS/United States ; P30 CA082709/CA/NCI NIH HHS/United States ; R01 HL140961/HL/NHLBI NIH HHS/United States ; R01 EY025641/EY/NEI NIH HHS/United States ; R01 EY031939/EY/NEI NIH HHS/United States ; R01 CA167291/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Infant, Newborn ; Angiogenesis Inhibitors/pharmacology/therapeutic use ; Core Binding Factor Alpha 2 Subunit ; *Diabetic Retinopathy/drug therapy ; Epoxide Hydrolases ; Inflammation/drug therapy ; *Macular Degeneration/drug therapy ; *Retinopathy of Prematurity/drug therapy ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; },
abstract = {Neovascular eye diseases include conditions such as retinopathy of prematurity, proliferative diabetic retinopathy, and neovascular age-related macular degeneration. Together, they are a major cause of vision loss and blindness worldwide. The current therapeutic mainstay for these diseases is intravitreal injections of biologics targeting vascular endothelial growth factor (VEGF) signaling. Lack of universal response to these anti-VEGF agents coupled with the challenging delivery method underscore a need for new therapeutic targets and agents. In particular, proteins that mediate both inflammatory and proangiogenic signaling are appealing targets for new therapeutic development. Here, we review agents currently in clinical trials and highlight some promising targets in preclinical and early clinical development, focusing on the redox-regulatory transcriptional activator APE1/Ref-1, the bioactive lipid modulator soluble epoxide hydrolase, the transcription factor RUNX1, and others. Small molecules targeting each of these proteins show promise for blocking neovascularization and inflammation. The affected signaling pathways illustrate the potential of new antiangiogenic strategies for posterior ocular disease. SIGNIFICANCE STATEMENT: Discovery and therapeutic targeting of new angiogenesis mediators is necessary to improve treatment of blinding eye diseases like retinopathy of prematurity, diabetic retinopathy, and neovascular age-related macular degeneration. Novel targets undergoing evaluation and drug discovery work include proteins important for both angiogenesis and inflammation signaling, including APE1/Ref-1, soluble epoxide hydrolase, RUNX1, and others.},
}
@article {pmid37140901,
year = {2023},
author = {Wittenborn, JS and Lee, AY and Lundeen, EA and Lamuda, P and Saaddine, J and Su, GL and Lu, R and Damani, A and Zawadzki, JS and Froines, CP and Shen, JZ and Kung, TH and Yanagihara, RT and Maring, M and Takahashi, MM and Blazes, M and Rein, DB},
title = {Validity of Administrative Claims and Electronic Health Registry Data From a Single Practice for Eye Health Surveillance.},
journal = {JAMA ophthalmology},
volume = {141},
number = {6},
pages = {534-541},
pmid = {37140901},
issn = {2168-6173},
support = {U01 DP006444/DP/NCCDPHP CDC HHS/United States ; },
mesh = {Humans ; Female ; Aged ; Male ; Retrospective Studies ; *Big Data ; Cross-Sectional Studies ; Routinely Collected Health Data ; *Glaucoma ; Blindness ; },
abstract = {IMPORTANCE: Diagnostic information from administrative claims and electronic health record (EHR) data may serve as an important resource for surveillance of vision and eye health, but the accuracy and validity of these sources are unknown.<br><br>OBJECTIVE: To estimate the accuracy of diagnosis codes in administrative claims and EHRs compared to retrospective medical record review.<br><br>This cross-sectional study compared the presence and prevalence of eye disorders based on diagnostic codes in EHR and claims records vs clinical medical record review at University of Washington-affiliated ophthalmology or optometry clinics from May 2018 to April 2020. Patients 16 years and older with an eye examination in the previous 2 years were included, oversampled for diagnosed major eye diseases and visual acuity loss.<br><br>EXPOSURES: Patients were assigned to vision and eye health condition categories based on diagnosis codes present in their billing claims history and EHR using the diagnostic case definitions of the US Centers for Disease Control and Prevention Vision and Eye Health Surveillance System (VEHSS) as well as clinical assessment based on retrospective medical record review.<br><br>MAIN OUTCOME AND MEASURES: Accuracy was measured as area under the receiver operating characteristic curve (AUC) of claims and EHR-based diagnostic coding vs retrospective review of clinical assessments and treatment plans.<br><br>RESULTS: Among 669 participants (mean [range] age, 66.1 [16-99] years; 357 [53.4%] female), identification of diseases in billing claims and EHR data using VEHSS case definitions was accurate for diabetic retinopathy (claims AUC, 0.94; 95% CI, 0.91-0.98; EHR AUC, 0.97; 95% CI, 0.95-0.99), glaucoma (claims AUC, 0.90; 95% CI, 0.88-0.93; EHR AUC, 0.93; 95% CI, 0.90-0.95), age-related macular degeneration (claims AUC, 0.87; 95% CI, 0.83-0.92; EHR AUC, 0.96; 95% CI, 0.94-0.98), and cataracts (claims AUC, 0.82; 95% CI, 0.79-0.86; EHR AUC, 0.91; 95% CI, 0.89-0.93). However, several condition categories showed low validity with AUCs below 0.7, including diagnosed disorders of refraction and accommodation (claims AUC, 0.54; 95% CI, 0.49-0.60; EHR AUC, 0.61; 95% CI, 0.56-0.67), diagnosed blindness and low vision (claims AUC, 0.56; 95% CI, 0.53-0.58; EHR AUC, 0.57; 95% CI, 0.54-0.59), and orbital and external diseases (claims AUC, 0.63; 95% CI, 0.57-0.69; EHR AUC, 0.65; 95% CI, 0.59-0.70).<br><br>CONCLUSION AND RELEVANCE: In this cross-sectional study of current and recent ophthalmology patients with high rates of eye disorders and vision loss, identification of major vision-threatening eye disorders based on diagnosis codes in claims and EHR records was accurate. However, vision loss, refractive error, and other broadly defined or lower-risk disorder categories were less accurately identified by diagnosis codes in claims and EHR data.},
}
@article {pmid37139441,
year = {2023},
author = {Álvarez-Barrios, A and Álvarez, L and Artime, E and García, M and Lengyel, I and Pereiro, R and González-Iglesias, H},
title = {Altered zinc homeostasis in a primary cell culture model of the retinal pigment epithelium.},
journal = {Frontiers in nutrition},
volume = {10},
number = {},
pages = {1124987},
pmid = {37139441},
issn = {2296-861X},
abstract = {The retinal pigment epithelium (RPE) is progressively degenerated during age-related macular degeneration (AMD), one of the leading causes of irreversible blindness, which clinical hallmark is the buildup of sub-RPE extracellular material. Clinical observations indicate that Zn dyshomeostasis can initiate detrimental intracellular events in the RPE. In this study, we used a primary human fetal RPE cell culture model producing sub-RPE deposits accumulation that recapitulates features of early AMD to study Zn homeostasis and metalloproteins changes. RPE cell derived samples were collected at 10, 21 and 59 days in culture and processed for RNA sequencing, elemental mass spectrometry and the abundance and cellular localization of specific proteins. RPE cells developed processes normal to RPE, including intercellular unions formation and expression of RPE proteins. Punctate deposition of apolipoprotein E, marker of sub-RPE material accumulation, was observed from 3 weeks with profusion after 2 months in culture. Zn cytoplasmic concentrations significantly decreased 0.2 times at 59 days, from 0.264 ± 0.119 ng·μg[-1] at 10 days to 0.062 ± 0.043 ng·μg[-1] at 59 days (p < 0.05). Conversely, increased levels of Cu (1.5-fold in cytoplasm, 5.0-fold in cell nuclei and membranes), Na (3.5-fold in cytoplasm, 14.0-fold in cell nuclei and membranes) and K (6.8-fold in cytoplasm) were detected after 59-days long culture. The Zn-regulating proteins metallothioneins showed significant changes in gene expression over time, with a potent down-regulation at RNA and protein level of the most abundant isoform in primary RPE cells, from 0.141 ± 0.016 ng·mL[-1] at 10 days to 0.056 ± 0.023 ng·mL[-1] at 59 days (0.4-fold change, p < 0.05). Zn influx and efflux transporters were also deregulated, along with an increase in oxidative stress and alterations in the expression of antioxidant enzymes, including superoxide dismutase, catalase and glutathione peroxidase. The RPE cell model producing early accumulation of extracellular deposits provided evidences on an altered Zn homeostasis, exacerbated by changes in cytosolic Zn-binding proteins and Zn transporters, along with variations in other metals and metalloproteins, suggesting a potential role of altered Zn homeostasis during AMD development.},
}
@article {pmid37137441,
year = {2023},
author = {Karema-Jokinen, V and Koskela, A and Hytti, M and Hongisto, H and Viheriälä, T and Liukkonen, M and Torsti, T and Skottman, H and Kauppinen, A and Nymark, S and Kaarniranta, K},
title = {Crosstalk of protein clearance, inflammasome, and Ca[2+] channels in retinal pigment epithelium derived from age-related macular degeneration patients.},
journal = {The Journal of biological chemistry},
volume = {299},
number = {6},
pages = {104770},
pmid = {37137441},
issn = {1083-351X},
mesh = {Aged ; Humans ; Autophagy ; Inflammasomes/metabolism ; Inflammation/metabolism ; *Macular Degeneration/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; },
abstract = {Degeneration and/or dysfunction of retinal pigment epithelium (RPE) is generally detected as the formation of intracellular and extracellular protein aggregates, called lipofuscin and drusen, respectively, in patients with age-related macular degeneration (AMD), the leading cause of blindness in the elderly population. These clinical hallmarks are linked to dysfunctional protein homeostasis and inflammation and furthermore, are both regulated by changes in intracellular Ca[2+] concentration. While many other cellular mechanisms have been considered in the investigations of AMD-RPE, there has been relatively little work on understanding the interactions of protein clearance, inflammation, and Ca[2+] dynamics in disease pathogenesis. Here we established induced pluripotent stem cell-derived RPE from two patients with advanced AMD and from an age- and gender-matched control subject. We studied autophagy and inflammasome activation under disturbed proteostasis in these cell lines and investigated changes in their intracellular Ca[2+] concentration and L-type voltage-gated Ca[2+] channels. Our work demonstrated dysregulated autophagy and inflammasome activation in AMD-RPE accompanied by reduced intracellular free Ca[2+] levels. Interestingly, we found currents through L-type voltage-gated Ca[2+] channels to be diminished and showed these channels to be significantly localized to intracellular compartments in AMD-RPE. Taken together, the alterations in Ca[2+] dynamics in AMD-RPE together with dysregulated autophagy and inflammasome activation indicate an important role for Ca[2+] signaling in AMD pathogenesis, providing new avenues for the development of therapeutic approaches.},
}
@article {pmid37133840,
year = {2023},
author = {Soga, H and Inoue, T and Urade, Y and Ueta, T and Kawashima, H and Kaburaki, T and Aihara, M},
title = {Attenuation of Laser-Induced Choroidal Neovascularization by Blockade of Prostaglandin D2 Receptor 2.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {5},
pages = {5},
pmid = {37133840},
issn = {2164-2591},
mesh = {Mice ; Humans ; Animals ; *Vascular Endothelial Growth Factor A/genetics/therapeutic use ; Prostaglandin D2/pharmacology/therapeutic use ; *Choroidal Neovascularization/drug therapy ; Lasers ; Human Umbilical Vein Endothelial Cells/metabolism ; Mice, Knockout ; },
abstract = {PURPOSE: The purpose of this study was to investigate the impact of prostaglandin D2 (PGD2) receptor 2 (DP2) on choroidal neovascularization (CNV) formation in mice.<br><br>METHODS: Using a laser-induced CNV model, the CNV size of wild-type (WT) mice treated with DP2 antagonist (CAY10471 or OC000459) was compared with that of untreated mice. Vascular endothelial growth factor (VEGF) and MCP-1 levels were also compared between the two groups. Similar experiments were performed comparing DP2 knockout (DP2KO) mice with WT mice (8 and 56 weeks old). The number of infiltrating macrophages to laser spots was also compared between the WT and DP2KO mice. We administered a DP2 antagonist to 15-methyl PGD2 (a DP2 agonist)-stimulated ARPE-19 cells and measured VEGF secretion by enzyme-linked immunosorbent assay. Tube formation assay was performed on human umbilical vein endothelial cells with or without a DP2 antagonist.<br><br>RESULTS: CNV sizes were significantly smaller in mice treated with CAY10471 or OC000459 than in those treated with vehicle. Similarly, the CNV size of DP2KO mice was significantly smaller than that of WT mice. The number of macrophages at laser spots in DP2KO mice was significantly lower than that in WT mice. The VEGF concentration of lasered DP2KO mice's eyes was significantly lower than that of lasered WT mice' eyes. DP2 antagonist treatment suppressed VEGF secretion in ARPE-19 cells under 15-methyl PGD2 stimulation. The tube formation assay suggested that lumen formation was inhibited by a DP2 antagonist.<br><br>CONCLUSIONS: DP2 blockade attenuated choroidal neovascularization.<br><br>TRANSLATIONAL RELEVANCE: Drugs targeting DP2 are potentially a novel treatment for age-related macular degeneration.},
}
@article {pmid37133500,
year = {2023},
author = {Oncel, D and Corradetti, G and Wakatsuki, Y and Nittala, MG and Velaga, SB and Stambolian, D and Pericak-Vance, MA and Haines, JL and Sadda, SR},
title = {Drusen morphometrics on optical coherence tomography in eyes with age-related macular degeneration and normal aging.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {9},
pages = {2525-2533},
pmid = {37133500},
issn = {1435-702X},
support = {R01 EY023164/EY/NEI NIH HHS/United States ; R01 EY030614/EY/NEI NIH HHS/United States ; RO1EY023164/EY/NEI NIH HHS/United States ; R01EY030614/EY/NEI NIH HHS/United States ; RO1EY023164/EY/NEI NIH HHS/United States ; R01EY030614/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Retinal Drusen/diagnosis ; *Macular Degeneration/diagnosis ; Retina ; Aging ; Fluorescein Angiography ; },
abstract = {PURPOSE: To compare drusen size metrics (apical height and basal width) on optical coherence tomography (OCT) B-scans with their size assessed on color photos in eyes with age-related macular degeneration (AMD) and normal aging.<br><br>METHODS: A total of 508 drusen were evaluated in this analysis. Flash color fundus photos (CFP), infrared reflectance (IR) images, and OCT B-scans obtained at the same visit were evaluated. Individual drusen were identified on CFPs and the diameters of the drusen were measured in planimetric grading software. CFPs were manually registered to the IR image with their corresponding OCT volume. After confirming correspondence between the CFP and OCT, the apical height and basal width of the same drusen were measured on OCT B-scans.<br><br>RESULTS: Drusen were divided into small, medium, large, and very large categories based on their diameter on the CFP images (<&#x2009;63, 63 to 124, 125 to 249, and [Formula: see text] 250&#xa0;&#x3bc;m, respectively). The OCT apical height of small drusen on CFP ranged from 20 to 31&#xa0;&#x3bc;m, while medium drusen ranged from 31 to 46&#xa0;&#x3bc;m, large drusen ranged from 45&#xa0;&#x3bc;m to 111&#xa0;&#xb5;m, and very large drusen ranged from 55&#xa0;&#x3bc;m to 208&#xa0;&#x3bc;m. The OCT basal width measured&#x2009;<&#x2009;99&#xa0;&#x3bc;m in small drusen, from 99 to 143&#xa0;&#x3bc;m in medium drusen, from 141 to 407&#xa0;&#xb5;m in large drusen, and&#x2009;>&#x2009;209&#xa0;&#xb5;m in very large drusen.<br><br>CONCLUSION: Drusen of different size categories on color photographs may also be separated according to their apical height and basal width on OCT. The apical height and basal width ranges defined in this analysis may be of value in the design of an OCT-based grading scale for AMD.},
}
@article {pmid37131780,
year = {2023},
author = {Zhu, S and Xu, R and Engel, AL and Wang, Y and McNeel, R and Hurley, JB and Chao, JR and Du, J},
title = {Proline provides a nitrogen source in the retinal pigment epithelium to synthesize and export amino acids for the neural retina.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37131780},
issn = {2692-8205},
support = {R01 EY034364/EY/NEI NIH HHS/United States ; P20 GM144230/GM/NIGMS NIH HHS/United States ; R01 EY031324/EY/NEI NIH HHS/United States ; R01 EY032462/EY/NEI NIH HHS/United States ; P20 GM103434/GM/NIGMS NIH HHS/United States ; },
abstract = {It is known that metabolic defects in the retinal pigment epithelium (RPE) can cause degeneration of its neighboring photoreceptors in the retina, leading to retinal degenerative diseases such as age-related macular degeneration. However, how RPE metabolism supports the health of the neural retina remains unclear. The retina requires exogenous nitrogen sources for protein synthesis, neurotransmission, and energy metabolism. Using 15N tracing coupled with mass spectrometry, we found human RPE can utilize the nitrogen in proline to produce and export 13 amino acids, including glutamate, aspartate, glutamine, alanine and serine. Similarly, we found this proline nitrogen utilization in the mouse RPE/choroid but not in the neural retina of explant cultures. Co-culture of human RPE with the retina showed that the retina can take up the amino acids, especially glutamate, aspartate and glutamine, generated from proline nitrogen in the RPE. Intravenous delivery of 15N proline in vivo demonstrated 15N-derived amino acids appear earlier in the RPE before the retina. We also found proline dehydrogenase (PRODH), the key enzyme in proline catabolism is highly enriched in the RPE but not the retina. The deletion of PRODH blocks proline nitrogen utilization in RPE and the import of proline nitrogen-derived amino acids in the retina. Our findings highlight the importance of RPE metabolism in supporting nitrogen sources for the retina, providing insight into understanding the mechanisms of the retinal metabolic ecosystem and RPE-initiated retinal degenerative diseases.},
}
@article {pmid37130462,
year = {2023},
author = {Ma, JYW and Greferath, U and Wong, JHC and Fothergill, LJ and Jobling, AI and Vessey, KA and Fletcher, EL},
title = {Aging induces cell loss and a decline in phagosome processing in the mouse retinal pigment epithelium.},
journal = {Neurobiology of aging},
volume = {128},
number = {},
pages = {1-16},
doi = {10.1016/j.neurobiolaging.2023.03.003},
pmid = {37130462},
issn = {1558-1497},
mesh = {Mice ; Animals ; *Retinal Pigment Epithelium ; Mice, Inbred C57BL ; *Phagocytosis/genetics ; Phagosomes/metabolism ; Aging/genetics ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and dysfunction in the retinal pigment epithelium (RPE) with age is known to contribute to disease development. The aim of this study was to investigate how the C57BL/6J mouse RPE changes with age. RPE structure was found to change with age and eccentricity, with cell size increasing, nuclei lost, and tight junctions altered in the peripheral retina. Phagocytosis of photoreceptor outer segments (POS) by the RPE was investigated using gene expression analysis and histology. RNA-Seq transcriptomic gene profiling of the RPE showed a downregulation of genes involved in phagosome processing and histological analysis showed a decline in phagosome-lysosome association in the aged tissue. In addition, failures in the autophagy pathway that modulates intracellular waste degradation were observed in the aged RPE tissue. These findings highlight that RPE cell loss and slowing of POS processing contribute to RPE dysfunction with age and may predispose the aging eye to AMD development.},
}
@article {pmid37126699,
year = {2023},
author = {Luu, JC and Saadane, A and Leinonen, H and Choi, EH and Gao, F and Lewandowski, D and Halabi, M and Sander, CL and Wu, A and Wang, JM and Singh, R and Gao, S and Lessieur, EM and Dong, Z and Palczewska, G and Mullins, RF and Peachey, NS and Kiser, PD and Tabaka, M and Kern, TS and Palczewski, K},
title = {Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {19},
pages = {e2221045120},
pmid = {37126699},
issn = {1091-6490},
support = {P30 EY011373/EY/NEI NIH HHS/United States ; IK6 BX003604/BX/BLRD VA/United States ; I01 BX004939/BX/BLRD VA/United States ; S10 RR025496/RR/NCRR NIH HHS/United States ; T32 EY024236/EY/NEI NIH HHS/United States ; IK6 BX005233/BX/BLRD VA/United States ; S10 OD010794/OD/NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; P30 EY034070/EY/NEI NIH HHS/United States ; R01 EY009339/EY/NEI NIH HHS/United States ; S10 OD021718/OD/NIH HHS/United States ; R01 EY022938/EY/NEI NIH HHS/United States ; R01 EY030873/EY/NEI NIH HHS/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; R24 EY027283/EY/NEI NIH HHS/United States ; F30 EY031566/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Retina/metabolism ; *Retinal Degeneration/metabolism ; *Retinitis Pigmentosa/metabolism ; *Macular Degeneration/pathology ; *Diabetic Retinopathy/metabolism ; },
abstract = {Chronic, progressive retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa, arise from genetic and environmental perturbations of cellular and tissue homeostasis. These disruptions accumulate with repeated exposures to stress over time, leading to progressive visual impairment and, in many cases, legal blindness. Despite decades of research, therapeutic options for the millions of patients suffering from these disorders remain severely limited, especially for treating earlier stages of pathogenesis when the opportunity to preserve the retinal structure and visual function is greatest. To address this urgent, unmet medical need, we employed a systems pharmacology platform for therapeutic development. Through integrative single-cell transcriptomics, proteomics, and phosphoproteomics, we identified universal molecular mechanisms across distinct models of age-related and inherited retinal degenerations, characterized by impaired physiological resilience to stress. Here, we report that selective, targeted pharmacological inhibition of cyclic nucleotide phosphodiesterases (PDEs), which serve as critical regulatory nodes that modulate intracellular second messenger signaling pathways, stabilized the transcriptome, proteome, and phosphoproteome through downstream activation of protective mechanisms coupled with synergistic inhibition of degenerative processes. This therapeutic intervention enhanced resilience to acute and chronic forms of stress in the degenerating retina, thus preserving tissue structure and function across various models of age-related and inherited retinal disease. Taken together, these findings exemplify a systems pharmacology approach to drug discovery and development, revealing a new class of therapeutics with potential clinical utility in the treatment or prevention of the most common causes of blindness.},
}
@article {pmid37126685,
year = {2023},
author = {Chang, YJ and Jenny, LA and Li, YS and Cui, X and Kong, Y and Li, Y and Sparrow, JR and Tsang, SH},
title = {CRISPR editing demonstrates rs10490924 raised oxidative stress in iPSC-derived retinal cells from patients with ARMS2/HTRA1-related AMD.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {19},
pages = {e2215005120},
pmid = {37126685},
issn = {1091-6490},
support = {R21 AG050437/AG/NIA NIH HHS/United States ; R01 EY018213/EY/NEI NIH HHS/United States ; U01 EY034590/EY/NEI NIH HHS/United States ; U01 EY030580/EY/NEI NIH HHS/United States ; R01 EY009076/EY/NEI NIH HHS/United States ; R01 EY026682/EY/NEI NIH HHS/United States ; R24 EY027285/EY/NEI NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; U54 OD020351/OD/NIH HHS/United States ; R01 EY024698/EY/NEI NIH HHS/United States ; P30 EY019007/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; High-Temperature Requirement A Serine Peptidase 1/genetics ; *Induced Pluripotent Stem Cells/metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats ; Proteins/metabolism ; Serine Endopeptidases/genetics ; Genome-Wide Association Study ; *Macular Degeneration/genetics ; Oxidative Stress ; Polymorphism, Single Nucleotide ; Complement Factor H/genetics ; Genotype ; },
abstract = {Genome-wide association studies (GWAS) have identified genetic risk loci for age-related macular degeneration (AMD) on the chromosome 10q26 (Chr10) locus and are tightly linked: the A69S (G>T) rs10490924 single-nucleotide variant (SNV) and the AATAA-rich insertion-deletion (indel, del443/ins54), which are found in the age-related maculopathy susceptibility 2 (ARMS2) gene, and the G512A (G>A) rs11200638 SNV, which is found in the high-temperature requirement A serine peptidase 1 (HTRA1) promoter. The fourth variant is Y402H complement factor H (CFH), which directs CFH signaling. CRISPR manipulation of retinal pigment epithelium (RPE) cells may allow one to isolate the effects of the individual SNV and thus identify SNV-specific effects on cell phenotype. Clustered regularly interspaced short palindromic repeats (CRISPR) editing demonstrates that rs10490924 raised oxidative stress in induced pluripotent stem cell (iPSC)-derived retinal cells from patients with AMD. Sodium phenylbutyrate preferentially reverses the cell death caused by ARMS2 rs10490924 but not HTRA1 rs11200638. This study serves as a proof of concept for the use of patient-specific iPSCs for functional annotation of tightly linked GWAS to study the etiology of a late-onset disease phenotype. More importantly, we demonstrate that antioxidant administration may be useful for reducing reactive oxidative stress in AMD, a prevalent late-onset neurodegenerative disorder.},
}
@article {pmid37125931,
year = {2023},
author = {Bakri, SJ and Bektas, M and Sharp, D and Luo, R and Sarda, SP and Khan, S},
title = {Geographic atrophy: Mechanism of disease, pathophysiology, and role of the complement system.},
journal = {Journal of managed care &amp; specialty pharmacy},
volume = {29},
number = {5-a Suppl},
pages = {S2-S11},
pmid = {37125931},
issn = {2376-1032},
mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy/etiology ; Angiogenesis Inhibitors/therapeutic use ; Activities of Daily Living ; Quality of Life ; *Wet Macular Degeneration/drug therapy ; Vascular Endothelial Growth Factor A ; Visual Acuity ; Complement System Proteins/therapeutic use ; Pharmaceutical Preparations ; },
abstract = {Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD), characterized by atrophic lesions that first start in the outer retina and progressively expand to cover the macula and the fovea, the center of the macula, leading to irreversible loss of vision over time. GA is distinct from wet or neovascular AMD (nAMD), the other form of advanced AMD. Neovascular AMD is characterized by new invading leaky blood vessels in the macula that can lead to acute vision loss. GA and nAMD may coexist in the same eye. The underlying pathophysiology of GA is complex and thought to involve chronic inflammation due to overactivation of the complement system that leads to the loss of photoreceptors, retinal pigment epithelium (RPE), and the underlying choriocapillaris. The disappearance of these structures appears as sharply demarcated atrophic lesions that are typical of GA. Researchers have reported about 1 million reported cases of GA in the United States, and about 160,000 cases occur per year. The most important risk factors for GA are increasing age and family history. Diagnosis of GA is usually made by using multimodal imaging techniques. Lesions associated with GA are highly heterogeneous, and the growth rate may differ from patient to patient. Despite the progressive nature of GA, the fovea may be spared until much later in the disease, thereby retaining central vision in patients. With time, atrophic lesions may progressively grow to involve the fovea, thereby severely impairing central vision. Vision loss can happen rapidly once the lesions reach the fovea. However, even without the involvement of the fovea, ongoing vision impairment impacting daily life may be present. Median time from GA not involving the center of the fovea (without subfoveal involvement) to GA with lesion boundary affecting the foveal center (subfoveal involvement) ranges from 1.4 to 2.5 years. GA can greatly impact patients' functioning and quality of life and limit their independence by interfering with activities of daily living, including difficulties with reading, driving, watching television, recognizing faces, and being unable to do household chores. No treatments have been available until intravitreal pegcetacoplan was recently approved by the US Food and Drug Administration for GA secondary to AMD. DISCLOSURES: Dr Bakri serves as a consultant to Apellis Pharmaceuticals, as well as AbbVie, Adverum, Eyepoint, iLumen, Iveric Bio, Genentech, Novartis, Outlook Therapeutics, Pixium, Regeneron, Roche, and Regenxbio. Drs Sharp, Luo, and Sarda are employees of Apellis Pharmaceuticals. Dr Bektas and Ms Khan are employees of RTI Health Solutions. Apellis developed and led the concept design of this publication, review and interpretation, approval, and decision to publish. This research was developed under a research contract between RTI Health Solutions and Apellis Pharmaceuticals and was funded by Apellis Pharmaceuticals. This supplement is to describe the disease of geographic atrophy and was funded by Apellis. Apellis Pharmaceuticals has developed Syfovre (pegcetacoplan), the first and only treatment for geographic atrophy.},
}
@article {pmid37125790,
year = {2023},
author = {Zhang, Q and Autterson, G and Miller, JML},
title = {Improved Lipofuscin Models and Quantification of Outer Segment Phagocytosis Capacity in Highly Polarized Human Retinal Pigment Epithelial Cultures.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {194},
pages = {},
pmid = {37125790},
issn = {1940-087X},
support = {K08 EY033420/EY/NEI NIH HHS/United States ; S10 OD028612/OD/NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Lipofuscin/metabolism ; *Retinal Pigments/metabolism ; Phagocytosis/physiology ; Retinal Pigment Epithelium ; Cell Line ; Cells, Cultured ; },
abstract = {The daily phagocytosis of photoreceptor outer segments by the retinal pigment epithelium (RPE) contributes to the accumulation of an intracellular aging pigment termed lipofuscin. The toxicity of lipofuscin is well established in Stargardt's disease, the most common inherited retinal degeneration, but is more controversial in age-related macular degeneration (AMD), the leading cause of irreversible blindness in the developed world. Determining lipofuscin toxicity in humans has been difficult, and animal models of Stargardt's have limited toxicity. Thus, in vitro models that mimic human RPE in vivo are needed to better understand lipofuscin generation, clearance, and toxicity. The majority of cell culture lipofuscin models to date have been in cell lines or have involved feeding RPE a single component of the complex lipofuscin mixture rather than fragments/tips of the entire photoreceptor outer segment, which generates a more complete and physiologic lipofuscin model. Described here is a method to induce the accumulation of lipofuscin-like material (termed undigestible autofluorescence material, or UAM) in highly differentiated primary human pre-natal RPE (hfRPE) and induced pluripotent stem cell (iPSC) derived RPE. UAM accumulated in cultures by repeated feedings of ultraviolet light-treated OS fragments taken up by the RPE via phagocytosis. The key ways that UAM approximates and differs from lipofuscin in vivo are also discussed. Accompanying this model of lipofuscin-like accumulation, imaging methods to distinguish the broad autofluorescence spectrum of UAM granules from concurrent antibody staining are introduced. Finally, to assess the impact of UAM on RPE phagocytosis capacity, a new method for quantifying outer segment fragment/tips uptake and breakdown has been introduced. Termed "Total Consumptive Capacity", this method overcomes potential misinterpretations of RPE phagocytosis capacity inherent in classic outer segment "pulse-chase" assays. The models and techniques introduced here can be used to study lipofuscin generation and clearance pathways and putative toxicity.},
}
@article {pmid37123974,
year = {2023},
author = {Dörschmann, P and Seeba, C and Thalenhorst, T and Roider, J and Klettner, A},
title = {Anti-inflammatory properties of antiangiogenic fucoidan in retinal pigment epithelium cells.},
journal = {Heliyon},
volume = {9},
number = {4},
pages = {e15202},
pmid = {37123974},
issn = {2405-8440},
abstract = {Age-related macular degeneration (AMD) is a multifactorial disease in which angiogenesis, oxidative stress and inflammation are important contributing factors. In this study, we investigated the anti-inflammatory effects of a fucoidan from the brown algae Fucus vesiculosus (FV) in primary porcine RPE cells. Inflammation was induced by lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (Poly I:C), Pam2CSK4 (Pam), or tumor necrosis factor alpha (TNF-α). Cell viability was tested with thiazolyl blue tetrazolium bromide (MTT) test, barrier function by measuring transepithelial electric resistance (TEER), interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion in ELISA, retinal pigment epithelium-specific 65 kDa protein (RPE65) and protectin (CD59) expression in Western blot, gene expression with quantitative polymerase chain reaction (qPCR) (IL6, IL8, MERTK, PIK3CA), and phagocytotic activity in a microscopic assay. FV fucoidan did not influence RPE cell viability. FV fucoidan reduced the Poly I:C proinflammatory cytokine secretion of IL-6 and IL-8. In addition, it decreased the expression of IL-6 and IL-8 in RT-PCR. LPS and TNF-α reduced the expression of CD59 in Western blot, this reduction was lost under FV fucoidan treatment. Also, LPS and TNF-α reduced the expression of visual cycle protein RPE65, this reduction was again lost under FV fucoidan treatment. Furthermore, the significant reduction of barrier function after Poly I:C stimulation is ameliorated by FV fucoidan. Concerning phagocytosis, however, the inflammation-induced reduction was not improved by FV fucoidan. FV and proinflammatory milieu did not relevantly influence phagocytosis relevant gene expression either. In conclusion, we show that fucoidan from FV can reduce proinflammatory stimulation in RPE induced by toll-like receptor 3 (TLR-3) activation and is of high interest as a potential compound for early AMD treatment.},
}
@article {pmid37120456,
year = {2023},
author = {Mai, J and Lachinov, D and Riedl, S and Reiter, GS and Vogl, WD and Bogunovic, H and Schmidt-Erfurth, U},
title = {Clinical validation for automated geographic atrophy monitoring on OCT under complement inhibitory treatment.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {7028},
pmid = {37120456},
issn = {2045-2322},
mesh = {Humans ; Female ; Animals ; Horses ; *Geographic Atrophy/diagnostic imaging ; Artificial Intelligence ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; Retinal Pigment Epithelium ; },
abstract = {Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials.},
}
@article {pmid37120204,
year = {2023},
author = {Morand-Laffargue, L and Hirschberg, J and Halimi, C and Desmarchelier, C and Borel, P},
title = {The zeaxanthin present in a tomato line rich in this carotenoid is as bioavailable as that present in the food sources richest in this xanthophyll.},
journal = {Food research international (Ottawa, Ont.)},
volume = {168},
number = {},
pages = {112751},
doi = {10.1016/j.foodres.2023.112751},
pmid = {37120204},
issn = {1873-7145},
mesh = {Humans ; *Lutein ; Zeaxanthins ; *Solanum lycopersicum ; Caco-2 Cells ; Xanthophylls ; Carotenoids ; },
abstract = {It is strongly suspected that, like lutein, zeaxanthin (ZEA) plays a biological role in the human eye. Many studies also suggest that it could reduce the risk of age-related macular degeneration and improve cognition. Unfortunately, it is only present in a very limited number of foods. This is why a new tomato line, named "Xantomato", whose fruits can synthesize this compound, was generated. However, whether ZEA in Xantomato is bioavailable enough for Xantomato to qualify as a nutritionally relevant ZEA source is not known. The objective was to compare the bioaccessibility and intestinal cell uptake efficiency of ZEA from Xantomato to that present in the richest sources of this compound. Bioaccessibility was assessed using in vitro digestions and uptake efficiency using Caco-2 cells. Xantomato ZEA bioaccessibility was not statistically different from that of common fruits and vegetables rich in this compound. Xantomato ZEA uptake efficiency (7.8%) was lower (P < 0.05) than that of orange pepper (10.6%) but not different from that of corn (6.9%). Therefore, the results of the in vitro digestion/Caco-2 cell model suggest that Xantomato ZEA could be as bioavailable as that found in common food sources of this compound.},
}
@article {pmid37119082,
year = {2023},
author = {Jung, W and Han, K and Kim, B and Hwang, S and Yoon, JM and Park, J and Lim, DH and Shin, DW},
title = {Age-Related Macular Degeneration With Visual Disability Is Associated With Cardiovascular Disease Risk in the Korean Nationwide Cohort.},
journal = {Journal of the American Heart Association},
volume = {12},
number = {9},
pages = {e028027},
pmid = {37119082},
issn = {2047-9980},
mesh = {Humans ; Female ; Cohort Studies ; *Cardiovascular Diseases/diagnosis/epidemiology/complications ; Risk Factors ; *Macular Degeneration/diagnosis/epidemiology ; *Myocardial Infarction/epidemiology/complications ; *Ischemic Stroke/complications ; Republic of Korea/epidemiology ; },
abstract = {Background Age-related macular degeneration (AMD) is the leading cause of visual disability. AMD shares some risk factors with the pathogenesis of cardiovascular disease (CVD). However, previous studies examining the association between AMD and the risk of CVD provide conflicting results. Hence, we investigated the association between AMD, visual disability, and the risk of CVD. Methods and Results This is a nationwide cohort study using data from the Korean National Health Insurance System database (2009-2019) on subjects who underwent a national health screening program in 2009. A total of 3 789 963 subjects were categorized by the presence of AMD and visual disability. Visual disability was defined as a best-corrected visual acuity of ≤20/100 by validated documentation from a specialist physician. Cox regression hazard model was used to examine the hazard ratios (HRs) of CVD, including myocardial infarction and ischemic stroke, after adjusting for potential confounders. During a mean 9.77 years of follow-up, AMD was associated with a 5% higher risk of myocardial infarction (adjusted HR [aHR], 1.05 [95% CI, 1.01-1.10]) but not associated with increased risk of overall CVD (aHR, 1.02 [95% CI, 1.00-1.05]) or ischemic stroke (aHR, 1.02 [95% CI, 0.98-1.06]). However, when AMD was accompanied by visual disability, there was increased risk of CVD (aHR, 1.17 [95% CI, 1.06-1.29]), myocardial infarction (aHR, 1.18 [95% CI, 1.01-1.37]), and ischemic stroke (aHR, 1.20 [95% CI, 1.06-1.35]). These trends were more evident in women and subjects with cardiometabolic comorbidities. Conclusions AMD with visual disability, but not all AMD, was associated with an increased risk of CVD. Patients with AMD who have visual disability should be targeted for CVD prevention.},
}
@article {pmid37118942,
year = {2023},
author = {Hunter, AML and Anderson, RS and Redmond, T and Garway-Heath, DF and Mulholland, PJ},
title = {Investigating the linkage between mesopic spatial summation and variations in retinal ganglion cell density across the central visual field.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {43},
number = {5},
pages = {1179-1189},
doi = {10.1111/opo.13158},
pmid = {37118942},
issn = {1475-1313},
support = {/DH_/Department of Health/United Kingdom ; },
mesh = {Humans ; Middle Aged ; *Visual Fields ; Retinal Ganglion Cells ; Visual Field Tests ; Regression Analysis ; *Color Vision ; },
abstract = {PURPOSE: The relationship between perimetric stimulus area and Ricco's area (RA) determines measured thresholds and the sensitivity of perimetry to retinal disease. The nature of this relationship, in addition to effect of retinal ganglion cell (RGC) number on this, is currently unknown for the adaptation conditions of mesopic microperimetry. In this study, achromatic mesopic spatial summation was measured across the central visual field to estimate RA with the number of RGCs underlying RA also being established.<br><br>METHODS: Achromatic luminance thresholds were measured for six incremental spot stimuli (0.009-2.07&#x2009;deg[2]) and 190.4&#x2009;ms duration, at four locations, each at 2.5&#xb0;, 5&#xb0; and 10&#xb0; eccentricity in five healthy observers (mean age 61.4&#x2009;years) under mesopic conditions (background 1.58&#x2009;cd/m[2]). RA was estimated using two-phase regression analysis with the number of RGCs underlying RA being calculated using normative histological RGC counts.<br><br>RESULTS: Ricco's area exhibited a small but statistically insignificant increase between 2.5&#xb0; and 10&#xb0; eccentricity. Compared with photopic conditions, RA was larger, with the difference between RA and the Goldmann III stimulus (0.43&#xb0;) being minimised. RGC number underlying RA was also higher than reported for photopic conditions (median 70 cells, IQR 36-93), with no significant difference being observed across test locations.<br><br>CONCLUSIONS: Ricco's area and the number of RGCs underlying RA do not vary significantly across the central visual field in mesopic conditions. However, RA is larger and more similar to the standard perimetric Goldmann III stimulus under mesopic compared with photopic adaptation conditions. Further work is required to determine if compensatory enlargements in RA occur in age-related macular degeneration, to establish the optimal stimulus parameters for AMD-specific microperimetry.},
}
@article {pmid37116544,
year = {2023},
author = {Oganov, AC and Seddon, I and Jabbehdari, S and Uner, OE and Fonoudi, H and Yazdanpanah, G and Outani, O and Arevalo, JF},
title = {Artificial intelligence in retinal image analysis: Development, advances, and challenges.},
journal = {Survey of ophthalmology},
volume = {68},
number = {5},
pages = {905-919},
doi = {10.1016/j.survophthal.2023.04.001},
pmid = {37116544},
issn = {1879-3304},
mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; *Macular Edema/diagnosis ; Artificial Intelligence ; Tomography, Optical Coherence/methods ; Retina/diagnostic imaging/pathology ; Fluorescein Angiography/methods ; },
abstract = {Modern advances in diagnostic technologies offer the potential for unprecedented insight into ophthalmic conditions relating to the retina. We discuss the current landscape of artificial intelligence in retina with respect to screening, diagnosis, and monitoring of retinal pathologies such as diabetic retinopathy, diabetic macular edema, central serous chorioretinopathy, and age-related macular degeneration. We review the methods used in these models and evaluate their performance in both research and clinical contexts and discuss potential future directions for investigation, use of multiple imaging modalities in artificial intelligence algorithms, and challenges in the application of artificial intelligence in retinal pathologies.},
}
@article {pmid37114419,
year = {2023},
author = {McGuinness, MB and Robman, LD and McNeil, JJ and Tran, C and Woods, RL and Owen, AJ and Pham, T and Guymer, RH},
title = {Self-rated eyesight among healthy older Australians: Baseline results of the ASPREE Longitudinal Study of Older Persons.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {51},
number = {5},
pages = {413-424},
pmid = {37114419},
issn = {1442-9071},
support = {U01 AG029824/AG/NIA NIH HHS/United States ; U19 AG062682/AG/NIA NIH HHS/United States ; },
mesh = {Male ; Aged, 80 and over ; *Health Status ; *Vision Disorders/epidemiology ; Female ; Longitudinal Studies ; Aged ; Australia/epidemiology ; Cross-Sectional Studies ; Humans ; Self Report ; Australasian People ; Vision, Ocular ; },
abstract = {We aimed to describe the self-reported level of eyesight amongst a cohort of relatively healthy older Australian adults, and to investigate associations between poorer self-rated eyesight and demographic, health, and functional characteristics METHODS: The ASPirin in Reducing Events in the Elderly (ASPREE) Longitudinal Study of Older Persons (ALSOP) study was embedded in a multisite trial which recruited independently living Australians from general practices (2010-2014). Self-rated eyesight was recorded on a paper-based questionnaire as Excellent, Good, Fair, Poor, Very poor, or Completely blind at the baseline study wave RESULTS: Data from 14 592 participants (aged 70-95 years, 54.61% female) were included in this cross-sectional analysis. Eighty percent of participants reported excellent or good eyesight (n = 11 677). People with complete blindness were precluded from enrolling but 299 participants (2.0%) reported poor or very poor eyesight, and 2616 rated their eyesight as fair (17.9%). Lower levels of eyesight were associated with being older, female, fewer years of formal education, a primary language other than English, smoking, and self-reported macular degeneration, glaucoma, retinopathy, cataracts, and hearing problems (each p ≤ 0.021). People with lower levels of eyesight had a higher number of falls, frailty characteristics, and depressive symptoms, and lower mental and physical health functioning scores (each p < 0.001) CONCLUSIONS: Whilst most of these healthy older Australians reported good or excellent eyesight, a notable minority reported poor or very poor eyesight, and this was associated with a range of poorer health measures. These findings support the need for additional resources to prevent vision loss and associated sequelae.},
}
@article {pmid37111749,
year = {2023},
author = {Yaylaci, S and Dinç, E and Aydın, B and Tekinay, AB and Guler, MO},
title = {Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous.},
journal = {Pharmaceutics},
volume = {15},
number = {4},
pages = {},
pmid = {37111749},
issn = {1999-4923},
abstract = {Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature-a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye's posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration.},
}
@article {pmid37111377,
year = {2023},
author = {Khalili, H and Kashkoli, HH and Weyland, DE and Pirkalkhoran, S and Grabowska, WR},
title = {Advanced Therapy Medicinal Products for Age-Related Macular Degeneration; Scaffold Fabrication and Delivery Methods.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
pmid = {37111377},
issn = {1424-8247},
abstract = {Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal degenerative disease. Whilst antibody-based drugs have revolutionised treatment of neovascular AMD, they are only effective at an early stage and cannot prevent eventual progression or allow recovery of previously lost vision. Hence, there is a clear unmet need to find innovative treatment strategies to develop a long-term cure. The replacement of damaged retinal cells is thought to be the best therapeutic strategy for the treatment of patients with retinal degeneration. Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products including cell therapy medicinal products, gene therapy medicinal products, and tissue engineered products. Development of ATMPs for the treatment of retinal degeneration diseases has become a fast-growing field of research because it offers the potential to replace damaged retinal cells for long-term treatment of AMD. While gene therapy has shown encouraging results, its effectiveness for treatment of retinal disease may be hampered by the body's response and problems associated with inflammation in the eye. In this mini-review, we focus on describing ATMP approaches including cell- and gene-based therapies for treatment of AMD along with their applications. We also aim to provide a brief overview of biological substitutes, also known as scaffolds, that can be used for delivery of cells to the target tissue and describe biomechanical properties required for optimal delivery. We describe different fabrication methods for preparing cell-scaffolds and explain how the use of artificial intelligence (AI) can aid with the process. We predict that combining AI with 3D bioprinting for 3D cell-scaffold fabrication could potentially revolutionise retinal tissue engineering and open up new opportunities for developing innovative platforms to deliver therapeutic agents to the target tissues.},
}
@article {pmid37111318,
year = {2023},
author = {Kikushima, W and Sakurada, Y and Fukuda, Y and Matsubara, M and Kotoda, Y and Sugiyama, A and Kashiwagi, K},
title = {A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
pmid = {37111318},
issn = {1424-8247},
abstract = {We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4-8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1-2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10[-7]). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10[-3] and 1.0 × 10[-3], respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept.},
}
@article {pmid37111251,
year = {2023},
author = {Desmettre, T and Mainster, MA and Ledesma-Gil, G},
title = {Half-Fluence, Half-Dose Photodynamic Therapy: Less Direct Damage but More Inflammation?.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
pmid = {37111251},
issn = {1424-8247},
abstract = {Objective: To present clinical findings and multimodal imaging of three patients who developed bacillary layer detachments (BALADs) shortly after half-fluence, half-dose (HFHD) verteporfin photodynamic therapy (PDT). Methods: Retrospective observational case series. Three patients were treated with HFHD-PDT for (1) macular neovascularisation five years after resolved central serous chorioretinopathy (CSC), (2) persistent serous retinal detachment (SRD) from chronic CSC, and (3) neovascular age-related macular degeneration with persistent SRD despite intravitreal anti-VEGF therapy. Results: Each patient developed a BALAD after HFHD-PDT. Acute fulminant exudation caused subretinal fluid expansion into the inner photoreceptor layer, cleaving myoid from ellipsoid zones in the central macula. Subretinal fluid and the BALADs subsequently resolved over 6-8 weeks. Conclusions: The subretinal fluid and BALAD following HFHD-PDT were transient and did not cause photoreceptor damage over a 6-month follow-up period. We speculate that the reduced-impact HFHD protocol decreases direct tissue damage but increases proinflammatory cytokines. The long-term pathophysiological consequences of the resolved BALADs are unknown.},
}
@article {pmid37110558,
year = {2023},
author = {Caruso, G and Fresta, CG and Fidilio, A and Lazzara, F and Musso, N and Cardaci, V and Drago, F and Caraci, F and Bucolo, C},
title = {Carnosine Counteracts the Molecular Alterations Aβ Oligomers-Induced in Human Retinal Pigment Epithelial Cells.},
journal = {Molecules (Basel, Switzerland)},
volume = {28},
number = {8},
pages = {},
pmid = {37110558},
issn = {1420-3049},
support = {CUP E65F21002640005//PON REACT project (Azione IV.4-"Dottorati e contratti di ricerca su tematiche dell'innovazione", nuovo Asse IV del PON Ricerca e Innovazione 2014-2020 "Istruzione e ricerca per il recupe-ro-REACT-EU")/ ; RC2022-N4//Italian Ministry of Health Research Program/ ; },
mesh = {Humans ; *Carnosine/pharmacology/metabolism ; Retina/metabolism ; Amyloid beta-Peptides/metabolism ; Retinal Pigment Epithelium/metabolism ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; *Macular Degeneration/metabolism ; Dipeptides/pharmacology ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Age-related macular degeneration (AMD) has been described as a progressive eye disease characterized by irreversible impairment of central vision, and unfortunately, an effective treatment is still not available. It is well-known that amyloid-beta (Aβ) peptide is one of the major culprits in causing neurodegeneration in Alzheimer's disease (AD). The extracellular accumulation of this peptide has also been found in drusen which lies under the retinal pigment epithelium (RPE) and represents one of the early signs of AMD pathology. Aβ aggregates, especially in the form of oligomers, are able to induce pro-oxidant (oxidative stress) and pro-inflammatory phenomena in RPE cells. ARPE-19 is a spontaneously arising human RPE cell line validated for drug discovery processes in AMD. In the present study, we employed ARPE-19 treated with Aβ oligomers, representing an in vitro model of AMD. We used a combination of methods, including ATPlite, quantitative real-time PCR, immunocytochemistry, as well as a fluorescent probe for reactive oxygen species to investigate the molecular alterations induced by Aβ oligomers. In particular, we found that Aβ exposure decreased the cell viability of ARPE-19 cells which was paralleled by increased inflammation (increased expression of pro-inflammatory mediators) and oxidative stress (increased expression of NADPH oxidase and ROS production) along with the destruction of ZO-1 tight junction protein. Once the damage was clarified, we investigated the therapeutic potential of carnosine, an endogenous dipeptide that is known to be reduced in AMD patients. Our findings demonstrate that carnosine was able to counteract most of the molecular alterations induced by the challenge of ARPE-19 with Aβ oligomers. These new findings obtained with ARPE-19 cells challenged with Aβ1-42 oligomers, along with the well-demonstrated multimodal mechanism of action of carnosine both in vitro and in vivo, able to prevent and/or counteract the dysfunctions elicited by Aβ oligomers, substantiate the neuroprotective potential of this dipeptide in the context of AMD pathology.},
}
@article {pmid37109604,
year = {2023},
author = {Ranetti, AE and Stanca, HT and Tăbăcaru, B and Teodoru, A and Munteanu, M and Stanca, S},
title = {Retromode Imaging in Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {4},
pages = {},
pmid = {37109604},
issn = {1648-9144},
mesh = {Humans ; *Retina/diagnostic imaging ; *Wet Macular Degeneration ; Tomography, Optical Coherence ; },
abstract = {Background and Objectives: Retromode is a relatively new retinal-imaging technique that is based on the transillumination principle and is obtained with a scanning laser ophthalmoscope that uses light in the infrared spectrum. The laser light penetrates into the deep retinal layers and the choroid. Retromode images are captured with a laterally displaced aperture, and the detector captures only the scattered light. The result is a high-contrast pseudo-three-dimensional image. Age-related macular degeneration (AMD) is a disabling retinal disease. AMD is characterized in its early stage by small and intermediate drusen formation, while the signs of intermediate AMD are large drusen and/or pigmentary abnormalities. Late AMD has two forms, geographic atrophy, which is the advanced form of dry AMD, and wet AMD. Most of the lesions of AMD are located in the outer layers of the retina. This new imaging method can provide a glimpse of the deep retinal layers' topographic changes in a non-invasive, fast, and effective way that can match the other imaging tools available. Materials and Methods: The literature review was performed by searching the PubMed database using the following combination of keywords: retromode imaging and age-related macular degeneration. Relevant images similar to the ones in the literature were identified and used as models. Results: The purpose of this article is to highlight the utility of incorporating retromode imaging into the multimodal evaluation of the retina in patients with AMD and to gather and integrate these findings into a brief but comprehensive paper. Conclusions: Retromode imaging is a good screening, diagnosis, and monitoring tool for patients with AMD.},
}
@article {pmid37109497,
year = {2023},
author = {Serban, D and Dascalu, AM and Arsene, AL and Tribus, LC and Vancea, G and Pantea Stoian, A and Costea, DO and Tudosie, MS and Stana, D and Cristea, BM and Nicolae, VA and Tudor, C and Costea, AC and Comandasu, M and Faur, M and Tanasescu, C},
title = {Gut Microbiota Dysbiosis in Diabetic Retinopathy-Current Knowledge and Future Therapeutic Targets.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
pmid = {37109497},
issn = {2075-1729},
abstract = {Diabetic retinopathy is one of the major causes of blindness today, despite important achievements in diagnosis and therapy. The involvement of a gut-retina axis is thought to be a possible risk factor for several chronic eye disease, such as glaucoma, age-related macular degeneration, uveitis, and, recently, diabetic retinopathy. Dysbiosis may cause endothelial disfunction and alter retinal metabolism. This review analyzes the evidence regarding changes in gut microbiota in patients with DR compared with diabetics and healthy controls (HCs). A systematic review was performed on PubMed, Web of Science, and Google Scholar for the following terms: "gut microbiota" OR "gut microbiome" AND "diabetic retinopathy". Ultimately, 9 articles published between 2020 and 2022 presenting comparative data on a total of 228 T2DM patients with DR, 220 patients with T2DM, and 118 HCs were analyzed. All of the studies found a distinctive microbial beta diversity in DR vs. T2DM and HC, characterized by an altered Firmicutes/Bacteroidetes ratio, a decrease in butyrate producers, and an increase in LPS-expressing and pro-inflammatory species in the Bacteroidetes and Proteobacteria phyla. The probiotic species Bifidobacterium and Lactobacillus were decreased when compared with T2DM. Gut microbiota influence retinal health in multiple ways and may represent a future therapeutic target in DR.},
}
@article {pmid37109349,
year = {2023},
author = {Chorev, M and Haderlein, J and Chandra, S and Menon, G and Burton, BJL and Pearce, I and McKibbin, M and Thottarath, S and Karatsai, E and Chandak, S and Kotagiri, A and Talks, J and Grabowska, A and Ghanchi, F and Gale, R and Hamilton, R and Antony, B and Garnavi, R and Mareels, I and Giani, A and Chong, V and Sivaprasad, S},
title = {A Multi-Modal AI-Driven Cohort Selection Tool to Predict Suboptimal Non-Responders to Aflibercept Loading-Phase for Neovascular Age-Related Macular Degeneration: PRECISE Study Report 1.},
journal = {Journal of clinical medicine},
volume = {12},
number = {8},
pages = {},
pmid = {37109349},
issn = {2077-0383},
support = {ICI70200030//Australian Research Council Training Centre in Cognitive Computing/ ; },
abstract = {Patients diagnosed with exudative neovascular age-related macular degeneration are commonly treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, response to treatment is heterogeneous, without a clinical explanation. Predicting suboptimal response at baseline will enable more efficient clinical trial designs for novel, future interventions and facilitate individualised therapies. In this multicentre study, we trained a multi-modal artificial intelligence (AI) system to identify suboptimal responders to the loading-phase of the anti-VEGF agent aflibercept from baseline characteristics. We collected clinical features and optical coherence tomography scans from 1720 eyes of 1612 patients between 2019 and 2021. We evaluated our AI system as a patient selection method by emulating hypothetical clinical trials of different sizes based on our test set. Our method detected up to 57.6% more suboptimal responders than random selection, and up to 24.2% more than any alternative selection criteria tested. Applying this method to the entry process of candidates into randomised controlled trials may contribute to the success of such trials and further inform personalised care.},
}
@article {pmid37109207,
year = {2023},
author = {Hammadi, S and Tzoumas, N and Ferrara, M and Meschede, IP and Lo, K and Harris, C and Lako, M and Steel, DH},
title = {Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {8},
pages = {},
pmid = {37109207},
issn = {2077-0383},
support = {MR/X001687/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {The complement system is crucial for immune surveillance, providing the body's first line of defence against pathogens. However, an imbalance in its regulators can lead to inappropriate overactivation, resulting in diseases such as age-related macular degeneration (AMD), a leading cause of irreversible blindness globally affecting around 200 million people. Complement activation in AMD is believed to begin in the choriocapillaris, but it also plays a critical role in the subretinal and retinal pigment epithelium (RPE) spaces. Bruch's membrane (BrM) acts as a barrier between the retina/RPE and choroid, hindering complement protein diffusion. This impediment increases with age and AMD, leading to compartmentalisation of complement activation. In this review, we comprehensively examine the structure and function of BrM, including its age-related changes visible through in vivo imaging, and the consequences of complement dysfunction on AMD pathogenesis. We also explore the potential and limitations of various delivery routes (systemic, intravitreal, subretinal, and suprachoroidal) for safe and effective delivery of conventional and gene therapy-based complement inhibitors to treat AMD. Further research is needed to understand the diffusion of complement proteins across BrM and optimise therapeutic delivery to the retina.},
}
@article {pmid37108627,
year = {2023},
author = {Pariente, A and Pérez-Sala, &#xc1; and Ochoa, R and Bobadilla, M and Villanueva-Martínez, &#xc1; and Peláez, R and Larráyoz, IM},
title = {Identification of 7-Ketocholesterol-Modulated Pathways and Sterculic Acid Protective Effect in Retinal Pigmented Epithelium Cells by Using Genome-Wide Transcriptomic Analysis.},
journal = {International journal of molecular sciences},
volume = {24},
number = {8},
pages = {},
pmid = {37108627},
issn = {1422-0067},
support = {PI19/01805//Instituto de Salud Carlos III/ ; CPII20/00029//Instituto de Salud Carlos III/ ; RTC2019-007399-1//Ministerio de Ciencia e Innovaci&#xf3;n/ ; },
mesh = {Humans ; *Transcriptome ; Ketocholesterols/pharmacology ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/metabolism ; Epithelium/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. AMD is characterized by the formation of lipidic deposits between the retinal pigment epithelium (RPE) and the choroid called drusen. 7-Ketocholesterol (7KCh), an oxidized-cholesterol derivative, is closely related to AMD as it is one of the main molecules accumulated in drusen. 7KCh induces inflammatory and cytotoxic responses in different cell types, and a better knowledge of the signaling pathways involved in its response would provide a new perspective on the molecular mechanisms that lead to the development of AMD. Furthermore, currently used therapies for AMD are not efficient enough. Sterculic acid (SA) attenuates the 7KCh response in RPE cells and is presented as an alternative to improve these therapies. By using genome-wide transcriptomic analysis in monkey RPE cells, we have provided new insight into 7KCh-induced signaling in RPE cells, as well as the protective capacity of SA. 7KCh modulates the expression of several genes associated with lipid metabolism, endoplasmic reticulum stress, inflammation and cell death and induces a complex response in RPE cells. The addition of SA successfully attenuates the deleterious effect of 7KCh and highlights its potential for the treatment of AMD.},
}
@article {pmid37108450,
year = {2023},
author = {Chen, NN and Chen, CY and Wang, JJ and Huang, HC and Chen, WD and Chen, CL and Yang, YH and Lin, MH and Kuo, TY and Lai, CH},
title = {Functional and Anatomical Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Exudative Age-Related Macular Degeneration with or without Obstructive Sleep Apnea.},
journal = {International journal of molecular sciences},
volume = {24},
number = {8},
pages = {},
pmid = {37108450},
issn = {1422-0067},
support = {CGRPG6L0021//Chiayi Chang Gung Memorial Hospital/ ; },
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Prospective Studies ; Vascular Endothelial Growth Factors ; *Macular Degeneration/complications/drug therapy ; *Sleep Apnea, Obstructive/complications/drug therapy ; Tomography, Optical Coherence/methods ; Treatment Outcome ; },
abstract = {(1) To investigate the functional and anatomical outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with exudative age-related macular degeneration (AMD) with or without obstructive sleep apnea (OSA); (2) In total, 65 patients with AMD with or without OSA who received three consecutive doses of intravitreal anti-VEGF injections were enrolled. The primary outcomes-best-corrected visual acuity (BCVA) and central macular thickness (CMT)-were assessed at 1 and 3 months. Moreover, morphological changes observed through optical coherence tomography were analyzed; (3) In total, 15 of the 65 patients had OSA and were included in the OSA group; the remaining 50 patients were included in the non-OSA (control) group. At 1 and 3 months after treatment, BCVA and CMT had improved but did not differ significantly between the groups. More patients in the OSA group demonstrated subretinal fluid (SRF) resorption at 3 months after treatment than in the non-OSA group (p = 0.009). Changes in other imaging biomarkers, such as intraretinal cysts, retinal pigment epithelium detachment, hyperreflective dots, and ellipsoid zone disruptions, did not differ significantly between the groups; (4) Our results suggest that the BCVA and CMT outcomes 3 months after anti-VEGF treatment are similar between patients with and without OSA. Moreover, patients with OSA may exhibit superior SRF resorption. A large-scale prospective study is mandatory to evaluate the association between SRF resorption and visual outcomes in AMD patients with OSA.},
}
@article {pmid37107259,
year = {2023},
author = {González-Zamora, J and Hernandez, M and Recalde, S and Bezunartea, J and Montoliu, A and Bilbao-Malavé, V and Llorente-González, S and García-Layana, A and Fernández-Robredo, P},
title = {Matrix Metalloproteinase 13 Is Associated with Age-Related Choroidal Neovascularization.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {4},
pages = {},
pmid = {37107259},
issn = {2076-3921},
support = {01/2019//Thea Laboratoires/ ; 2021-2022//Fundaci&#xf3;n Jes&#xfa;s Gangoiti Barrera/ ; CUN 2019//Multi&#xf3;pticas/ ; RD16/0008/0011//Instituto de Salud Carlos III/ ; RD21/0017/0027//Instituto de Salud Carlos III/ ; RD21/0002/0010//Instituto de Salud Carlos III/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of severe vision loss in older individuals in developed countries. Despite advances in our understanding of AMD, its pathophysiology remains poorly understood. Matrix metalloproteinases (MMPs) have been proposed to play a role in AMD development. In this study, we aimed to characterize MMP-13 in AMD. We used retinal pigment epithelial cells, a murine model of laser-induced choroidal neovascularization, and plasma samples from patients with neovascular AMD to conduct our study. Our results show that MMP13 expression significantly increased under oxidative stress conditions in cultured retinal pigment epithelial cells. In the murine model, MMP13 was overexpressed in both retinal pigment epithelial cells and endothelial cells during choroidal neovascularization. Additionally, the total MMP13 levels in the plasma of patients with neovascular AMD were significantly lower than those in the control group. This suggests a reduced diffusion from the tissues or release from circulating cells in the bloodstream, given that the number and function of monocytes have been reported to be deficient in patients with AMD. Although more studies are needed to elucidate the role of MMP13 in AMD, it could be a promising therapeutic target for treating AMD.},
}
@article {pmid37106625,
year = {2023},
author = {von der Emde, L and Saßmannshausen, M and Morelle, O and Rennen, G and Holz, FG and Wintergerst, MWM and Ach, T},
title = {Reliability of Retinal Layer Annotation with a Novel, High-Resolution Optical Coherence Tomography Device: A Comparative Study.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {10},
number = {4},
pages = {},
pmid = {37106625},
issn = {2306-5354},
support = {03/22//Ernst und Berta Grimmke Foundation/ ; O-137.0030//BONFOR GEROK/ ; },
abstract = {Optical coherence tomography (OCT) enables in vivo diagnostics of individual retinal layers in the living human eye. However, improved imaging resolution could aid diagnosis and monitoring of retinal diseases and identify potential new imaging biomarkers. The investigational high-resolution OCT platform (High-Res OCT; 853 nm central wavelength, 3 µm axial-resolution) has an improved axial resolution by shifting the central wavelength and increasing the light source bandwidth compared to a conventional OCT device (880 nm central wavelength, 7 µm axial-resolution). To assess the possible benefit of a higher resolution, we compared the retest reliability of retinal layer annotation from conventional and High-Res OCT, evaluated the use of High-Res OCT in patients with age-related macular degeneration (AMD), and assessed differences of both devices on subjective image quality. Thirty eyes of 30 patients with early/intermediate AMD (iAMD; mean age 75 ± 8 years) and 30 eyes of 30 age-similar subjects without macular changes (62 ± 17 years) underwent identical OCT imaging on both devices. Inter- and intra-reader reliability were analyzed for manual retinal layer annotation using EyeLab. Central OCT B-scans were graded for image quality by two graders and a mean-opinion-score (MOS) was formed and evaluated. Inter- and intra-reader reliability were higher for High-Res OCT (greatest benefit for inter-reader reliability: ganglion cell layer; for intra-reader reliability: retinal nerve fiber layer). High-Res OCT was significantly associated with an improved MOS (MOS 9/8, Z-value = 5.4, p < 0.01) mainly due to improved subjective resolution (9/7, Z-Value 6.2, p < 0.01). The retinal pigment epithelium drusen complex showed a trend towards improved retest reliability in High-Res OCT in iAMD eyes but without statistical significance. Improved axial resolution of the High-Res OCT benefits retest reliability of retinal layer annotation and improves perceived image quality and resolution. Automated image analysis algorithms could also benefit from the increased image resolution.},
}
@article {pmid37104942,
year = {2023},
author = {Girgis, JM and Liu, Y and Liang, MC and Baumal, CR and Duker, JS and Waheed, NK},
title = {Retinal Pigment Epithelium Aperture Preceding Collapse of Vascular and Avascular Pigment Epithelial Detachments Secondary to AMD.},
journal = {Retinal cases &amp; brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001435},
pmid = {37104942},
issn = {1937-1578},
abstract = {PURPOSE: To describe retinal pigment epithelium (RPE) aperture preceding the collapse of retinal pigment epithelium detachments (RPED) in eyes with neovascular and non-neovascular age-related macular degeneration (AMD).<br><br>METHODS: Medical records from five patients with RPE aperture associated with vascular and avascular RPED were reviewed between 2010 and 2021 at the New England Eye Center at Tufts Medical Center. Main outcome measures were analysis of RPE aperture characteristics and temporal course of RPED collapse.<br><br>RESULTS: RPE apertures were identified in six eyes from five women (mean age of 72.6 years). Two eyes had neovasacular AMD and four eyes had non-neovascular AMD. The RPE aperture initially appeared as a discontinuity at the apex of the RPED without rippling or retraction. Each aperture was associated with hypertransmission of OCT signal into the choroid as well as hyperreflective foci. The mean time between the appearance of the RPE aperture to near complete collapse of the RPED was 9 months. Following RPED collapse, one eye developed choroidal neovascularization, three eyes progressed to geographic atrophy, one eye had recurrence of the RPED, and one eye remained unchanged.<br><br>CONCLUSION: RPE aperture is a characteristic OCT finding that can be observed in avascular or vascularized RPED secondary to AMD. RPE apertures precede RPED collapse, which are most likely to occur within nine months of RPE aperture detection.},
}
@article {pmid37103235,
year = {2023},
author = {Muchuchuti, S and Viriri, S},
title = {Retinal Disease Detection Using Deep Learning Techniques: A Comprehensive Review.},
journal = {Journal of imaging},
volume = {9},
number = {4},
pages = {},
pmid = {37103235},
issn = {2313-433X},
abstract = {Millions of people are affected by retinal abnormalities worldwide. Early detection and treatment of these abnormalities could arrest further progression, saving multitudes from avoidable blindness. Manual disease detection is time-consuming, tedious and lacks repeatability. There have been efforts to automate ocular disease detection, riding on the successes of the application of Deep Convolutional Neural Networks (DCNNs) and vision transformers (ViTs) for Computer-Aided Diagnosis (CAD). These models have performed well, however, there remain challenges owing to the complex nature of retinal lesions. This work reviews the most common retinal pathologies, provides an overview of prevalent imaging modalities and presents a critical evaluation of current deep-learning research for the detection and grading of glaucoma, diabetic retinopathy, Age-Related Macular Degeneration and multiple retinal diseases. The work concluded that CAD, through deep learning, will increasingly be vital as an assistive technology. As future work, there is a need to explore the potential impact of using ensemble CNN architectures in multiclass, multilabel tasks. Efforts should also be expended on the improvement of model explainability to win the trust of clinicians and patients.},
}
@article {pmid37101379,
year = {2023},
author = {Wang, S and Chiu, CY and Wilson, AF and Bailey-Wilson, JE and Agron, E and Chew, EY and Ahn, J and Xiong, M and Fan, R},
title = {Gene-level association analysis of bivariate ordinal traits with functional regressions.},
journal = {Genetic epidemiology},
volume = {47},
number = {6},
pages = {409-431},
doi = {10.1002/gepi.22524},
pmid = {37101379},
issn = {1098-2272},
mesh = {Humans ; *Models, Genetic ; Phenotype ; *Macular Degeneration/genetics ; Computer Simulation ; Linear Models ; },
abstract = {In genetic studies, many phenotypes have multiple naturally ordered discrete values. The phenotypes can be correlated with each other. If multiple correlated ordinal traits are analyzed simultaneously, the power of analysis may increase significantly while the false positives can be controlled well. In this study, we propose bivariate functional ordinal linear regression (BFOLR) models using latent regressions with cumulative logit link or probit link to perform a gene-based analysis for bivariate ordinal traits and sequencing data. In the proposed BFOLR models, genetic variant data are viewed as stochastic functions of physical positions, and the genetic effects are treated as a function of physical positions. The BFOLR models take the correlation of the two ordinal traits into account via latent variables. The BFOLR models are built upon functional data analysis which can be revised to analyze the bivariate ordinal traits and high-dimension genetic data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Extensive simulation studies show that the likelihood ratio tests of the BFOLR models control type I errors well and have good power performance. The BFOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes, CFH and ARMS2, are found to strongly associate with eye drusen size, drusen area, age-related macular degeneration (AMD) categories, and AMD severity scale.},
}
@article {pmid37100863,
year = {2023},
author = {Zhang, RX and Wen, Y and Guo, DD and Xu, FR and Wang, GM and Wang, XR and Shi, YW and Ding, J and Jiang, Q and Jiang, WJ and Jonas, JB and Bi, HS},
title = {Intravitreal injection of fibrillin 2 (Fbn2) recombinant protein for therapy of retinopathy in a retina-specific Fbn2 knock-down mouse model.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {6865},
pmid = {37100863},
issn = {2045-2322},
mesh = {Male ; Mice ; Animals ; Fibrillin-2/genetics/metabolism ; Intravitreal Injections ; Mice, Inbred C57BL ; *Retina/metabolism ; *Macular Degeneration/metabolism ; Disease Models, Animal ; Recombinant Proteins/genetics/metabolism ; },
abstract = {Mutations in the extracellular matrix gene Fibrillin-2 (FBN2) are related to genetic macular degenerative disorders including age-related macular degeneration (AMD) and early-onset macular degeneration (EOMD). It was reported that the retinal protein expression of FBN2 was reduced in patients with AMD and EOMD. The effect of exogenously supplied fbn2 recombinant protein on fbn2-deficiency-related retinopathy was not known. Here we investigated the efficacy and molecular mechanism of intravitreally applied fibrin-2 recombinant protein in mice with fbn2-deficient retinopathy. The experimental study included groups (all n = 9) of adult C57BL/6J male mice which underwent no intervention, intravitreal injection of adeno-associated virus (AAV) empty vector or intravitreal injection of AAV-sh-fbn2 (adeno-associated virus for expressing short hairpin RNA for fibrillin-2) followed by three intravitreal injections of fbn2 recombinant protein, given in intervals of 8 days in doses of 0.30 μg, 0.75 μg, 1.50 μg, and 3.00 μg, respectively. Eyes with intravitreally applied AAV-sh-fbn2 as compared to eyes with injection of AAV-empty vector or developed an exudative retinopathy with involvement of the deep retinal layers, reduction in axial length and reduction in ERG amplitudes. After additional and repeated application of fbn2 recombinant protein, the retinopathy improved with an increase in retinal thickness and ERG amplitude, the mRNA and protein expression of transforming growth factor-beta (TGF-β1) and TGF-β binding protein (LTBP-1) increased, and axial length elongated, with the difference most marked for the dose of 0.75 μg of fbn2 recombinant protein. The observations suggest that intravitreally applied fbn2 recombinant protein reversed the retinopathy caused by an fbn2 knockdown.},
}
@article {pmid37099020,
year = {2023},
author = {Wang, JH and Wong, RCB and Liu, GS},
title = {Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {4},
pages = {32},
pmid = {37099020},
issn = {1552-5783},
mesh = {Humans ; Aged ; *Transcriptome ; Retina ; *Macular Degeneration/genetics ; Aging/genetics ; Neuroglia ; },
abstract = {PURPOSE: Age is the main risk factor for age-related macular degeneration (AMD), a leading cause of blindness in the elderly, with limited therapeutic options.<br><br>METHODS: Here, we analyze the transcriptomic characteristics and cellular landscape of the aging retinas from controls and patients with AMD.<br><br>RESULTS: We identify the aging genes in the neural retina, which are associated with innate immune response and inflammation. Deconvolution analysis reveals that the estimated proportions of M2 macrophages are significantly increased with both age and AMD severity. Moreover, we find that proportions of M&#xfc;ller glia are significantly increased only with age but not with AMD severity. Several genes associated with both age and AMD severity, particularly C1s and MR1, are strong positively correlated with the proportions of M&#xfc;ller glia.<br><br>CONCLUSIONS: Our studies expand the genetic and cellular landscape of AMD and provide avenues for further studies on the relationship between age and AMD.},
}
@article {pmid37097804,
year = {2023},
author = {Kar, SS and Cetin, H and Abraham, J and Srivastava, SK and Whitney, J and Madabhushi, A and Ehlers, JP},
title = {Novel Fractal-Based Sub-RPE Compartment OCT Radiomics Biomarkers Are Associated With Subfoveal Geographic Atrophy in Dry AMD.},
journal = {IEEE transactions on bio-medical engineering},
volume = {70},
number = {10},
pages = {2914-2921},
pmid = {37097804},
issn = {1558-2531},
support = {I01 CX002622/CX/CSRD VA/United States ; C06 RR012463/RR/NCRR NIH HHS/United States ; IK6 BX006185/BX/BLRD VA/United States ; P30 EY025585/EY/NEI NIH HHS/United States ; U24 CA199374/CA/NCI NIH HHS/United States ; U01 CA239055/CA/NCI NIH HHS/United States ; R01 HL158071/HL/NHLBI NIH HHS/United States ; R01 CA268287/CA/NCI NIH HHS/United States ; R01 CA249992/CA/NCI NIH HHS/United States ; R01 HL151277/HL/NHLBI NIH HHS/United States ; R01 CA216579/CA/NCI NIH HHS/United States ; R01 CA268207/CA/NCI NIH HHS/United States ; R01 CA202752/CA/NCI NIH HHS/United States ; R01 CA208236/CA/NCI NIH HHS/United States ; U01 CA248226/CA/NCI NIH HHS/United States ; I01 BX004121/BX/BLRD VA/United States ; R43 EB028736/EB/NIBIB NIH HHS/United States ; U01 CA269181/CA/NCI NIH HHS/United States ; R01 CA257612/CA/NCI NIH HHS/United States ; U54 CA254566/CA/NCI NIH HHS/United States ; R01 CA220581/CA/NCI NIH HHS/United States ; K23 EY022947/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; *Geographic Atrophy/diagnostic imaging/pathology ; Retrospective Studies ; Fractals ; Fluorescein Angiography ; Tomography, Optical Coherence/methods ; Atrophy/pathology ; },
abstract = {OBJECTIVE: The purpose of this study was to quantitatively characterize the shape of the sub-retinal pigment epithelium (sub-RPE, i.e., space bounded by RPE and Bruch's membrane) compartment on SD-OCT using fractal dimension (FD) features and evaluate their impact on risk of subfoveal geographic atrophy (sfGA) progression.<br><br>METHODS: This was an IRB-approved retrospective study of 137 subjects with dry age-related macular degeneration (AMD) with subfoveal GA. Based on sfGA status at year five, eyes were categorized as "Progressors" and "Non-progressors". FD analysis allows quantification of the degree of shape complexity and architectural disorder associated with a structure. To characterize the structural irregularities along the sub-RPE surface between the two groups of patients, a total of 15 shape descriptors of FD were extracted from the sub-RPE compartment of baseline OCT scans. The top four features were identified using minimum Redundancy maximum Relevance (mRmR) feature selection method and evaluated with Random Forest (RF) classifier using three-fold cross validation from the training set (N = 90). Classifier performance was subsequently validated on the independent test set (N = 47).<br><br>RESULTS: Using the top four FD features, a RF classifier yielded an AUC of 0.85 on the independent test set. Mean fractal entropy (p-value = 4.8e-05) was identified as the most significant biomarker; higher values of entropy being associated with greater shape disorder and risk for sfGA progression.<br><br>CONCLUSIONS: FD assessment holds promise for identifying high-risk eyes for GA progression.<br><br>SIGNIFICANCE: With further validation, FD features could be potentially used for clinical trial enrichment and assessments for therapeutic response in dry AMD patients.},
}
@article {pmid37096209,
year = {2023},
author = {Kato, N and Haruta, M and Furushima, K and Arai, R and Matsuo, Y and Yoshida, S},
title = {Decrease in Ocular Blood Flow Thirty Minutes After Intravitreal Injections of Brolucizumab and Aflibercept for Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1187-1192},
pmid = {37096209},
issn = {1177-5467},
abstract = {PURPOSE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents such as brolucizumab and aflibercept are used widely to treat neovascular age-related macular degeneration (nAMD); however; they may theoretically affect the ocular blood flow. We investigated the short-term changes in the ocular blood flow between eyes with nAMD treated with intravitreal brolucizumab injections (IVBr) and intravitreal aflibercept injections (IVA).<br><br>METHODS: This study included 21 eyes of 21 Japanese patients with nAMD treated with either IVBr or IVA at Kurume University Hospital from April 2021 through June 2022. The rates of ocular blood flow at the optic nerve head (ONH mean blur rate [MBR]-vessel) and at the choroid (CHOR MBR) were analyzed before and 30 minutes after injections using laser speckle flowgraphy.<br><br>RESULTS: In the IVBr-treated group, the ONH MBR-vessel and CHOR MBR rates decreased significantly by 10.6% and 16.9% from baseline to 30 minutes after IVBr, respectively. In the IVA-treated group, ONH MBR-vessel and CHOR MBR rates decreased significantly by 9.4% and 6.1% from baseline to 30 minutes after IVA, respectively. There was no significant difference in the rates of decrease in the ONH MBR-vessel or CHOR MBR between the IVBr-treated and IVA-treated groups.<br><br>CONCLUSION: Intravitreal injections of brolucizumab and aflibercept in eyes with nAMD cause significant decreases in ocular blood flow at the ONH and the choroid 30 minutes after injection. The rate of decrease in ocular blood flow was not significant between the eyes treated with brolucizumab and aflibercept. However, 3 of 10 eyes treated with brolucizumab but none of 11 eyes treated with aflibercept had more than a 30% decrease in the ocular blood flow at the choroid 30 minutes after injection.},
}
@article {pmid37095516,
year = {2023},
author = {Cao, S and Zhang, R and Jiang, A and Kuerban, M and Wumaier, A and Wu, J and Xie, K and Aizezi, M and Tuersun, A and Liang, X and Chen, R},
title = {Application effect of an artificial intelligence-based fundus screening system: evaluation in a clinical setting and population screening.},
journal = {Biomedical engineering online},
volume = {22},
number = {1},
pages = {38},
pmid = {37095516},
issn = {1475-925X},
support = {2019D01C004//Natural Science Foundation of Xinjiang Uygur Autonomous Region/ ; 2019Q145//Xinjiang Uygur Autonomous Region Innovation Environment (Talents, Bases) Special Project (Special Talent Project-Tianshan Youth Project)/ ; KDYY202018//The Pearl River Scholar Tianshan Talent Cooperation's Expert Studio Innovation Team/ ; 202102020736//Science and Technology Program of Guangzhou/ ; },
mesh = {Humans ; Artificial Intelligence ; Fundus Oculi ; *Diabetic Retinopathy ; *Macular Degeneration ; *Glaucoma ; Mass Screening/methods ; },
abstract = {BACKGROUND: To investigate the application effect of artificial intelligence (AI)-based fundus screening system in real-world clinical environment.<br><br>METHODS: A total of 637 color fundus images were included in the analysis of the application of the AI-based fundus screening system in the clinical environment and 20,355 images were analyzed in the population screening.<br><br>RESULTS: The AI-based fundus screening system demonstrated superior diagnostic effectiveness for diabetic retinopathy (DR), retinal vein occlusion (RVO) and pathological myopia (PM) according to gold standard referral. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of three fundus abnormalities were greater (all&#x2009;>&#x2009;80%) than those for age-related macular degeneration (ARMD), referable glaucoma and other abnormalities. The percentages of different diagnostic conditions were similar in both the clinical environment and the population screening.<br><br>CONCLUSIONS: In a real-world setting, our AI-based fundus screening system could detect 7 conditions, with better performance for DR, RVO and PM. Testing in the clinical environment and through population screening demonstrated the clinical utility of our AI-based fundus screening system in the early detection of ocular fundus abnormalities and the prevention of blindness.},
}
@article {pmid37095277,
year = {2024},
author = {Yusuf, IH and Henein, C and Sivaprasad, S},
title = {Infographic: Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: the ANCHOR study.},
journal = {Eye (London, England)},
volume = {38},
number = {Suppl 2},
pages = {39-40},
doi = {10.1038/s41433-023-02397-z},
pmid = {37095277},
issn = {1476-5454},
support = {MR/R000735/1//RCUK | Medical Research Council (MRC)/ ; },
mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage ; *Photochemotherapy/methods ; *Verteporfin/therapeutic use ; *Photosensitizing Agents/therapeutic use ; *Porphyrins/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Macular Degeneration/drug therapy ; Wet Macular Degeneration/drug therapy ; Visual Acuity/physiology ; Intravitreal Injections ; },
}
@article {pmid37095122,
year = {2023},
author = {Jun, SY and Hwang, DD},
title = {Short-term effect of intravitreal brolucizumab injections in patients with neovascular age-related macular degeneration on retinal nerve fiber layer thickness.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {6685},
pmid = {37095122},
issn = {2045-2322},
mesh = {Humans ; *Ranibizumab ; Angiogenesis Inhibitors ; Retrospective Studies ; Vascular Endothelial Growth Factor A/pharmacology ; Retinal Ganglion Cells ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Nerve Fibers ; Tomography, Optical Coherence ; },
abstract = {This study reported the short-term effects of intravitreal brolucizumab (IVB) on peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (nAMD). This retrospective observational case series included patients with nAMD treated with other anti-vascular endothelial growth factor (anti-VEGF) agents and subsequently switched to IVB because of poor response to those other agents on spectral domain optical coherence tomography (SD-OCT). Best-corrected visual acuity (BCVA), intraocular pressure, funduscopy, and SD-OCT were assessed at baseline, 2 weeks, 1 month, and 3 months after injection. Twenty-two patients were included in the study. In the IVB group, BCVA significantly improved 3 months after injection compared with baseline (0.45 ± 0.25 vs. 0.38 ± 0.25, p = 0.012). During the 3-month follow-up, compared with baseline, RNFL thicknesses of the global, superior temporal, inferior temporal, inferior nasal, nasal, and superior nasal sectors did not change substantially in the IVB group. However, temporal RNFL thickness significantly decreased at 1 month (p = 0.045), and the significance was lost at 3 months (p = 0.378). The central macular thickness of treated eyes significantly decreased compared with the baseline at every follow-up visit. IVB in patients with nAMD had morphological and functional visual gain effects without RNFL thinning during the short-term follow-up.},
}
@article {pmid37092114,
year = {2023},
author = {Staropoli, PC and Iyer, P and Gregori, G and Rosenfeld, PJ and Flynn, HW},
title = {Identification of macular neovascularization in central serous chorioretinopathy using swept-source OCT angiography.},
journal = {American journal of ophthalmology case reports},
volume = {30},
number = {},
pages = {101843},
pmid = {37092114},
issn = {2451-9936},
abstract = {PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) was used to detect the presence of macular neovascularization (MNV) in eyes with exudative central serous chorioretinopathy (CSCR).<br><br>OBSERVATIONS: Case 1 is a 73-year-old man using prednisolone drops with 20/40 vision and a retinal pigment epithelial detachment (PED) associated with subretinal fluid (SRF) and no clinical signs of age-related macular degeneration (AMD) in his left eye. Three months after presentation he underwent SS-OCTA imaging that revealed MNV. He received a series of intravitreal anti-vascular endothelial growth factor (VEGF) injections and SS-OCTA imaging showed a decrease in the MNV lesion size with resolution of the SRF. VA improved to 20/25. Case 2 is a 65-year-old man with recent oral steroid use, presenting with 20/20 vision, a PED, SRF, and no evidence of AMD. SS-OCTA imaging at presentation revealed MNV, which worsened on interval SS-OCTA imaging after the patient deferred treatment. Intravitreal anti-VEGF therapy was then performed with resolution of the SRF and VA improved to 20/15. A total of six cases of type 1 MNV were diagnosed with CSCR. Most were men with a history of steroid or testosterone use and were treated with good response.<br><br>CONCLUSIONS AND IMPORTANCE: SS-OCTA imaging provides a convenient non-invasive strategy for identifying CSCR eyes with MNV without the need for dye-based angiography.},
}
@article {pmid37089700,
year = {2022},
author = {Chen, Y and Zhou, Y and Zhu, X and Yan, G and Pan, D and Wang, L and Yang, M and Wang, K},
title = {PET imaging of retinal inflammation in mice exposed to blue light using [[18]F]-DPA-714.},
journal = {Molecular vision},
volume = {28},
number = {},
pages = {507-515},
pmid = {37089700},
issn = {1090-0535},
mesh = {Mice ; Animals ; Tissue Distribution ; *Fluorine Radioisotopes ; Mice, Inbred C57BL ; *Inflammation/diagnostic imaging ; Positron-Emission Tomography/methods ; Retina/diagnostic imaging ; Carrier Proteins ; },
abstract = {PURPOSE: Positron emission tomography (PET) is widely used in high-precision imaging, which may provide a simple and noninvasive method for the detection of pathology and therapeutic effects. [[18]F]-DPA-714 is a second-generation translocator protein (TSPO) positron emission tomography radiotracer that shows great promise in a model of neuroinflammation. In this study, [[18]F]-DPA-714 micro-PET imaging was used to evaluate retinal inflammation in mice exposed to blue light, a well-established model of age-related macular degeneration (AMD) for molecular mechanism research and drug screening.<br><br>METHODS: C57BL/6J melanized mice were subjected to 10,000, 15,000, and 20,000&#xa0;lux blue light for 5 days (8 h/day) to develop the retinal injury model, and the structure and function of the retina were assessed using hematoxylin-eosin (HE) staining, electroretinography (ERG), and terminal-deoxynucleotidyl transferase (TdT)-mediated nick-end labeling (TUNEL) immunostaining. Then, [[18]F]-DPA-714 was injected approximately 100 &#x3bc;Ci through each tail vein, and static imaging was performed 1 h after injection. Finally, the mice eyeballs were collected for biodistribution and immune analysis.<br><br>RESULTS: The blue light exposure significantly destroyed the structure and function of the retina, and the uptake of [[18]F]-DPA-714 in the retinas of the mice exposed to blue light were the most significantly upregulated, which was consistent with the biodistribution data. In addition, the immunohistochemical, western blot, and immunofluorescence data showed an increase in microglial TSPO expression.<br><br>CONCLUSIONS: [[18]F]-DPA-714 micro-PET imaging might be a good method for evaluating early inflammatory status during retinal pathology.},
}
@article {pmid37089696,
year = {2022},
author = {Lauwen, S and Bakker, B and de Jong, EK and Fauser, S and Hoyng, CB and Lefeber, DJ and den Hollander, AI},
title = {Analysis of hemopexin plasma levels in patients with age-related macular degeneration.},
journal = {Molecular vision},
volume = {28},
number = {},
pages = {536-543},
pmid = {37089696},
issn = {1090-0535},
mesh = {Humans ; *Hemopexin/genetics ; *Macular Degeneration/genetics/metabolism ; Genotype ; Complement Factor H/genetics/metabolism ; Transcription Factors/genetics ; Polymorphism, Single Nucleotide/genetics ; },
abstract = {PURPOSE: A protein quantitative trait locus (pQTL) analysis recently revealed a strong association between hemopexin (HPX) levels and genetic variants at the complement factor H (CFH) locus. In this study, we aimed to determine HPX plasma levels in patients with age-related macular degeneration (AMD) and to compare them with those in controls. We also investigated whether genetic variants at the CFH locus are associated with HPX plasma levels.<br><br>METHODS: HPX levels were quantified in 200 advanced AMD cases and 200 controls using an enzyme-linked immunosorbent assay and compared between the two groups. Furthermore, HPX levels were analyzed per genotype group of three HPX-associated variants (rs61818956, rs10494745, and rs10801582) and four AMD-associated variants (rs794362 [proxy for rs187328863], rs570618, rs10922109, and rs61818924 [proxy for rs61818925]) at the CFH locus.<br><br>RESULTS: HPX levels were similar in the control group compared with the AMD group. The three variants at the CFH locus, which were previously associated with the HPX levels, showed no association with the HPX levels in our data set. No significant differences in HPX levels were detected between the different genotype groups of AMD-associated variants at the CFH locus.<br><br>CONCLUSIONS: In this study, HPX levels were not associated with AMD or AMD-associated variants at the CFH locus. The finding of a previous pQTL study that variants at the CFH locus were associated with HPX levels was also not confirmed in this study.},
}
@article {pmid37089564,
year = {2023},
author = {Zhang, Y and Wang, T and Wan, Z and Bai, J and Xue, Y and Dai, R and Wang, M and Peng, Q},
title = {Alterations of the intestinal microbiota in age-related macular degeneration.},
journal = {Frontiers in microbiology},
volume = {14},
number = {},
pages = {1069325},
pmid = {37089564},
issn = {1664-302X},
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50. Recently, intestinal microbiota has been reported to be involved in the pathogenesis of ocular diseases. The purpose of this study was to discover more about the involvement of the intestinal microbiota in AMD patients.<br><br>METHODS: Fecal samples from 30 patients with AMD (AMD group) and 17 age- and sex-matched healthy controls (control group) without any fundus disease were collected. DNA extraction, PCR amplification, and 16S rRNA gene sequencing of the samples were performed to identify intestinal microbial alterations. Further, we used BugBase for phenotypic prediction and PICRUSt2 for KEGG Orthology (KO) as well as metabolic feature prediction.<br><br>RESULTS: The intestinal microbiota was found to be significantly altered in the AMD group. The AMD group had a significantly lower level of Firmicutes and relatively higher levels of Proteobacteria and Bacteroidota compared to those in the control group. At the genus level, the AMD patient group showed a considerably higher proportion of Escherichia-Shigella and lower proportions of Blautia and Anaerostipes compared with those in the control group. Phenotypic prediction revealed obvious differences in the four phenotypes between the two groups. PICRUSt2 analysis revealed KOs and pathways associated with altered intestinal microbiota. The abundance of the top eight KOs in the AMD group was higher than that in the control group. These KOs were mainly involved in lipopolysaccharide biosynthesis.<br><br>CONCLUSION: The findings of this study indicated that AMD patients had different gut microbiota compared with healthy controls, and that AMD pathophysiology might be linked to changes in gut-related metabolic pathways. Therefore, intestinal microbiota might serve as non-invasive indicators for AMD clinical diagnosis and possibly also as AMD treatment targets.},
}
@article {pmid37088447,
year = {2023},
author = {Gabrielle, PH and Delyfer, MN and Glacet-Bernard, A and Conart, JB and Uzzan, J and Kodjikian, L and Arndt, C and Tadayoni, R and Soudry-Faure, A and Creuzot Garcher, CP},
title = {Surgery, Tissue Plasminogen Activator, Antiangiogenic Agents, and Age-Related Macular Degeneration Study: A Randomized Controlled Trial for Submacular Hemorrhage Secondary to Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {130},
number = {9},
pages = {947-957},
doi = {10.1016/j.ophtha.2023.04.014},
pmid = {37088447},
issn = {1549-4713},
mesh = {Humans ; Middle Aged ; Infant, Newborn ; *Tissue Plasminogen Activator/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Fibrinolytic Agents/therapeutic use ; Vascular Endothelial Growth Factor A ; Ranibizumab/therapeutic use ; Retinal Hemorrhage/drug therapy/etiology/surgery ; *Macular Degeneration/complications/drug therapy ; Retinal Pigment Epithelium ; Intravitreal Injections ; },
abstract = {PURPOSE: To compare the efficacy and the safety of submacular hemorrhage (SMH) management using either surgical pars plana vitrectomy (PPV) or pneumatic displacement (PD) with tissue plasminogen activator (tPA) and vascular endothelial growth factor (VEGF) inhibitor added to each arm.<br><br>DESIGN: Randomized, open-label, multicenter superiority study.<br><br>PARTICIPANTS: Ninety patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older with recent SMH (&#x2264; 14 days) of more than 2 optic disc areas and predominantly overlying the retinal pigment epithelium.<br><br>METHODS: Patients were assigned randomly to surgery (PPV, subretinal tPA [maximum, 0.5 ml/50 &#x3bc;g], and 20% sulfur hexafluoride [SF6] tamponade) or PD (0.05 ml intravitreal tPA [50 &#x3bc;g] and 0.3 ml intravitreal pure SF6). Both groups were asked to maintain a head upright position with the face forward at 45&#xb0; for 3 days after intervention and received 0.5 mg intravitreal ranibizumab at the end of the intervention, at months 1 and 2, as the loading phase, and then on a pro re nata regimen during a 6-month follow-up.<br><br>MAIN OUTCOME MEASURES: The primary efficacy endpoint was mean best-corrected visual acuity (VA) change at month 3. The secondary endpoints were mean VA change at month 6, 25-item National Eye Institute Visual Function Questionnaire composite score value at months 3 and 6, number of anti-VEGF injections, and complications during the 6-month follow-up.<br><br>RESULTS: Of the 90 patients randomized, 78 patients (86.7%) completed the 3-month efficacy endpoint visit. The mean VA change from baseline to month 3 in the surgery group (+16.8 letters [95% confidence interval (CI), 8.7-24.9 letters]) was not significantly superior to that in the PD group (+16.4 letters [95% CI, 7.1-25.7 letters]; adjusted difference &#x3b2;, 1.9 [-11.0; 14.9]; P&#xa0;= 0.767). Both groups achieved similar secondary outcomes at month 6. No unexpected ocular safety concerns were observed in either group.<br><br>CONCLUSIONS: Surgery did not yield superior visual gain nor additional benefit for SMH secondary to nAMD compared with PD at 3 months, with intravitreal anti-VEGF added to each arm. Both treatment strategies lead to a clinical improvement of VA without safety concerns for SMH over 6 months. Both design and results of the trial cannot be used to establish equivalence between treatments.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37086857,
year = {2023},
author = {MacCumber, MW and Wykoff, CC and Karcher, H and Adiguzel, E and Sinha, SB and Vishwakarma, S and LaPrise, A and Igwe, F and Freitas, R and Ip, MS and Zarbin, MA},
title = {One-Year Brolucizumab Outcomes in Neovascular Age-Related Macular Degeneration from a Large United States Cohort in the IRIS® Registry.},
journal = {Ophthalmology},
volume = {130},
number = {9},
pages = {937-946},
doi = {10.1016/j.ophtha.2023.04.012},
pmid = {37086857},
issn = {1549-4713},
mesh = {Humans ; Angiogenesis Inhibitors ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Registries ; Retrospective Studies ; United States/epidemiology ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/diagnosis/drug therapy/chemically induced ; },
abstract = {PURPOSE: To evaluate visual acuity (VA) and injection intervals in patients with neovascular age-related macular degeneration (nAMD) after 12 months of brolucizumab therapy in clinical practice.<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Adults in the United States-based IRIS&#xae; Registry (Intelligent Research in Sight) with nAMD who received brolucizumab exclusively for 12 months (2308 eyes of 2079 patients).<br><br>METHODS: Observational study of eyes with a first injection of brolucizumab (index), followed by 2 or more brolucizumab injections over the following 12 months without switching to another anti-vascular endothelial growth factor (VEGF) agent.<br><br>MAIN OUTCOME MEASURES: Primary outcomes were change in best recorded VA and, for eyes receiving prior anti-VEGF therapy (treatment-experienced eyes), the difference between the brolucizumab injection interval at 12 months and the anti-VEGF injection interval before switching. The interval before switching was defined as the time between the prior anti-VEGF and index brolucizumab injections; brolucizumab interval was the time between the closest injection to day 365 and the preceding injection. Secondary outcomes included incident adverse events.<br><br>RESULTS: Overall VA at index was 61.6 &#xb1; 18.4 Early Treatment Diabetic Retinopathy Study letters; 83.7% of treatment-naive eyes (184/220) and 86.1% of treatment-experienced eyes (1797/2088) showed stable (< 10 letters gained or lost) or improved (&#x2265; 10 letters gained) VA at 12 months. Among treatment-experienced eyes receiving a prior anti-VEGF injection within 365 days before index, 29.5% (594/2015) showed an interval before switching of 8 weeks or more (mean, 7.6 &#xb1; 5.5 weeks), whereas 83.1% (1734/2015) showed a brolucizumab injection interval at 12 months of 8 weeks or more (mean, 10.3 &#xb1; 4.0 weeks). In all, 77.1% of treatment-experienced eyes (1554/2015) showed an interval extension of 1 week or more; of these, 55.4% (861/1554) showed an extension of 4 weeks or more.<br><br>CONCLUSIONS: In this community-based study, at 12 months, brolucizumab treatment prolonged the interval between anti-VEGF injections for most treatment-experienced eyes, particularly those with shorter intervals before switching, while maintaining or improving VA. With careful balancing of the benefits and risks, switching to brolucizumab treatment may offer the advantage of extending the treatment interval for patients with a high anti-VEGF therapy burden.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}
@article {pmid37086257,
year = {2023},
author = {Blodi, BA and Domalpally, A and Corkery, E and Osborne, A and Blotner, S and Grzeschik, SM and Gune, S},
title = {Prevalence of Macular Atrophy in the MARINA Study of Ranibizumab versus Sham for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {8},
pages = {661-671},
doi = {10.1016/j.oret.2023.03.004},
pmid = {37086257},
issn = {2468-6530},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Prevalence ; Intravitreal Injections ; *Macular Degeneration/complications ; *Choroidal Neovascularization/diagnosis/drug therapy/epidemiology ; Atrophy/drug therapy ; Fibrosis ; },
abstract = {OBJECTIVE: Determine prevalence, progression rates, and associations of newly detectable macular atrophy (MA) in patients with choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD) with/without ranibizumab treatment.<br><br>DESIGN: Post hoc analysis of MA in patients with occult/minimally classic nAMD who received monthly intravitreal ranibizumab (0.3 or 0.5 mg) or sham injections for 24 months (M) in MARINA, a phase III trial in treatment-naive patients (NCT00056836).<br><br>PARTICIPANTS: Seven hundred six patients with nAMD: ranibizumab 0.3 mg, n&#xa0;= 236; 0.5 mg, n&#xa0;= 237; sham, n&#xa0;=&#xa0;233.<br><br>METHODS: Macular atrophy, assessed by color fundus photographs/fluorescein angiography, was classified as "within," "adjacent," or "nonadjacent" to the original CNV lesion. Factors associated with MA were assessed by multivariate logistic regression.<br><br>MAIN OUTCOME MEASURES: Prevalence/incidence of newly detectable MA over time, association with CNV area, MA progression rate, association of MA with visual acuity (VA), changes in CNV/leakage area, and factors predictive of new MA at 24M.<br><br>RESULTS: At 24M, new MA was detected in 36.8%, 40.4%, and 21.0% of eyes for ranibizumab 0.3 mg, 0.5 mg, and sham, respectively, most frequently within the area of the baseline CNV lesion (93.2%, 85.0%, and 69.0%). Rate of MA progression was similar across arms (&#x223c; 0.3 to 0.4 mm/year). There was strong association between absence of fibrosis and detectable MA (odds ratio, 2.7; 95% confidence interval [CI], 1.29-5.56), whereas an association was not identified between detectable MA and baseline VA, baseline fellow eye atrophy, ranibizumab treatment, or change in leakage/CNV area at 24M. Ranibizumab-treated eyes gained VA with (0.3 mg: 5.3 letters [95% CI, -3.3, 13.8]; 0.5 mg: 9.8 [4.7-15.0]) or without new MA (0.3 mg: 6.4 [4.1-8.6]; 0.5 mg: 8.0 [5.3-10.6]), whereas VA in sham-treated eyes deteriorated with/without new MA (-14.7 [-23.6, -5.8] and&#xa0;-14.0 [-16.9, -11.1], respectively).<br><br>CONCLUSIONS: New MA was more frequently detected in ranibizumab-treated than sham-treated eyes. Macular atrophy progression was similar across arms. Multivariate analysis showed that absence of fibrosis was the only variable associated with increased MA. Regardless of MA presence/location at baseline or throughout the study, ranibizumab-treated eyes showed clinically significant improvements in VA, whereas VA in sham-treated eyes worsened.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37085720,
year = {2024},
author = {Yusuf, IH and Henein, C and Sivaprasad, S},
title = {Infographic: Comparing the effectiveness of bevacizumab to ranibizumab in patients with exudative age-related macular degeneration: the BRAMD study.},
journal = {Eye (London, England)},
volume = {38},
number = {Suppl 2},
pages = {41-42},
doi = {10.1038/s41433-023-02398-y},
pmid = {37085720},
issn = {1476-5454},
support = {MR/R000735/1//RCUK | Medical Research Council (MRC)/ ; },
mesh = {Humans ; *Ranibizumab/therapeutic use/administration &amp; dosage ; *Bevacizumab/therapeutic use ; *Angiogenesis Inhibitors/therapeutic use ; *Wet Macular Degeneration/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Intravitreal Injections ; Antibodies, Monoclonal, Humanized/therapeutic use ; Visual Acuity ; Treatment Outcome ; Aged ; },
}
@article {pmid37084873,
year = {2023},
author = {Zhu, X and Zhou, C and Zhao, S and Zheng, Z},
title = {Role of m6A methylation in retinal diseases.},
journal = {Experimental eye research},
volume = {231},
number = {},
pages = {109489},
doi = {10.1016/j.exer.2023.109489},
pmid = {37084873},
issn = {1096-0007},
mesh = {Humans ; Methylation ; *Methyltransferases/genetics ; Epigenesis, Genetic ; RNA/metabolism ; *Retinal Diseases/genetics ; },
abstract = {Retinal diseases remain among the leading causes of visual impairment in developed countries, despite great efforts in prevention and early intervention. Due to the limited efficacy of current retinal therapies, novel therapeutic methods are urgently required. Over the past two decades, advances in next-generation sequencing technology have facilitated research on RNA modifications, which can elucidate the relevance of epigenetic mechanisms to disease. N6-methyladenosine (m6A), formed by methylation of adenosine at the N6-position, is the most widely studied RNA modification and plays an important role in RNA metabolism. It is dynamically regulated by writers (methyltransferases) and erasers (demethylases), and recognized by readers (m6A binding proteins). Although the discovery of m6A methylation can be traced back to the 1970s, its regulatory roles in retinal diseases are rarely appreciated. Here, we provide an overview of m6A methylation, and discuss its effects and possible mechanisms on retinal diseases, including diabetic retinopathy, age-related macular degeneration, retinoblastoma, retinitis pigmentosa, and proliferative vitreoretinopathy. Furthermore, we highlight potential agents targeting m6A methylation for retinal disease treatment and discuss the limitations and challenges of research in the field of m6A methylation.},
}
@article {pmid37084729,
year = {2023},
author = {Temple, S},
title = {Advancing cell therapy for neurodegenerative diseases.},
journal = {Cell stem cell},
volume = {30},
number = {5},
pages = {512-529},
pmid = {37084729},
issn = {1875-9777},
support = {R01 EY032138/EY/NEI NIH HHS/United States ; R35 NS097277/NS/NINDS NIH HHS/United States ; RF1 NS123568/NS/NINDS NIH HHS/United States ; U01 AG072464/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Neurodegenerative Diseases/therapy/genetics/pathology ; Central Nervous System/pathology ; Stem Cells/pathology ; Cell- and Tissue-Based Therapy ; },
abstract = {Cell-based therapies are being developed for various neurodegenerative diseases that affect the central nervous system (CNS). Concomitantly, the roles of individual cell types in neurodegenerative pathology are being uncovered by genetic and single-cell studies. With a greater understanding of cellular contributions to health and disease and with the arrival of promising approaches to modulate them, effective therapeutic cell products are now emerging. This review examines how the ability to generate diverse CNS cell types from stem cells, along with a deeper understanding of cell-type-specific functions and pathology, is advancing preclinical development of cell products for the treatment of neurodegenerative diseases.},
}
@article {pmid37082812,
year = {2023},
author = {Brizzi, F and Steiert, B and Pang, H and Diack, C and Lomax, M and Peck, R and Morgan, Z and Soubret, A},
title = {A model-based approach for historical borrowing, with an application to neovascular age-related macular degeneration.},
journal = {Statistical methods in medical research},
volume = {32},
number = {6},
pages = {1064-1081},
doi = {10.1177/09622802231155597},
pmid = {37082812},
issn = {1477-0334},
mesh = {Humans ; Bayes Theorem ; Cross-Sectional Studies ; *Models, Statistical ; Sample Size ; *Macular Degeneration/drug therapy ; Research Design ; Computer Simulation ; },
abstract = {Bayesian historical borrowing has recently attracted growing interest due to the increasing availability of historical control data, as well as improved computational methodology and software. In this article, we argue that the statistical models used for borrowing may be suboptimal when they do not adjust for differing factors across historical studies such as covariates, dosing regimen, etc. We propose an alternative approach to address these shortcomings. We start by constructing a historical model based on subject-level historical data to accurately characterize the control treatment by adjusting for known between trials differences. This model is subsequently used to predict the control arm response in the current trial, enabling the derivation of a model-informed prior for the treatment effect parameter of another (potentially simpler) model used to analyze the trial efficacy (i.e. the trial model). Our approach is applied to neovascular age-related macular degeneration trials, employing a cross-sectional regression trial model, and a longitudinal non-linear mixed-effects drug-disease-trial historical model. The latter model characterizes the relationship between clinical response, drug exposure and baseline covariates so that the derived model-informed prior seamlessly adapts to the trial population and can be extrapolated to a different dosing regimen. This approach can yield a more accurate prior for borrowing, thus optimizing gains in efficiency (e.g. increasing power or reducing the sample size) in future trials.},
}
@article {pmid37081576,
year = {2023},
author = {Airody, A and Baseler, HA and Seymour, J and Allgar, V and Mukherjee, R and Downey, L and Dhar-Munshi, S and Mahmood, S and Balaskas, K and Empeslidis, T and Hanson, RLW and Dorey, T and Szczerbicki, T and Sivaprasad, S and Gale, RP},
title = {The MATE trial: a multicentre, mixed-methodology, pilot, randomised controlled trial in neovascular age-related macular degeneration.},
journal = {Pilot and feasibility studies},
volume = {9},
number = {1},
pages = {63},
pmid = {37081576},
issn = {2055-5784},
abstract = {BACKGROUND/OBJECTIVES: In healthcare research investigating complex interventions, gaps in understanding of processes can be filled by using qualitative methods alongside a quantitative approach. The aim of this mixed-methods pilot trial was to provide feasibility evidence comparing two treatment regimens for neovascular age-related macular degeneration (nAMD) to inform a future large-scale randomised controlled trial (RCT).<br><br>SUBJECTS/METHODS: Forty-four treatment-na&#xef;ve nAMD patients were followed over 24&#xa0;months and randomised to one of two treatment regimens: standard care (SC) or treat and extend (T&amp;E). The primary objective evaluated feasibility of the MATE trial via evaluations of screening logs for recruitment rates, nonparticipation and screen fails, whilst qualitative in-depth interviews with key study staff evaluated the recruitment phase and running of the trial. The secondary objective assessed changes in visual acuity and central retinal thickness (CRT) between the two treatment arms.<br><br>RESULTS: The overall recruitment rate was 3.07 participants per month with a 40.8% non-participation rate, 18.51% screen-failure rate and 15% withdrawal/non-completion rate. Key themes in the recruitment phase included human factors, protocol-related issues, recruitment processes and challenges. Both treatment regimens showed a trend towards a visual acuity gain at month 12 which was not maintained at month 24, whilst CRT reduced similarly in both regimens over the same time period. These were achieved with one less treatment following a T&amp;E regimen.<br><br>CONCLUSION: This mixed-methodology, pilot RCT achieved its pre-defined recruitment, nonparticipation and screen failure rates, thus deeming it a success. With some minor protocol amendments, progression to a large-scale RCT will be achievable.},
}
@article {pmid37080383,
year = {2023},
author = {Li, Q and Hu, L and Liu, G and Yin, X and Li, Y and Wei, X and Duan, N and Zhao, X and Gong, Q and Du, Z},
title = {Inhibition of AIF-1 alleviates laser-induced macular neovascularization by inhibiting endothelial cell proliferation via restrained p44/42 MAPK signaling pathway.},
journal = {Experimental eye research},
volume = {231},
number = {},
pages = {109474},
doi = {10.1016/j.exer.2023.109474},
pmid = {37080383},
issn = {1096-0007},
mesh = {Mice ; Animals ; Vascular Endothelial Growth Factor A/metabolism ; Endothelial Cells/metabolism ; *Choroidal Neovascularization/metabolism ; Signal Transduction/physiology ; RNA, Small Interfering/genetics ; *Macular Degeneration/metabolism ; Cell Proliferation ; Lasers ; },
abstract = {Age-related macular degeneration (AMD) is a leading blinding disease worldwide, and macular neovascularization (MNV) is a common complication encountered in the advanced stages of AMD. While the underlying causes of MNV remain elusive, aberrant multiplication of choroidal endothelial cells (CECs) and increased vascular endothelial growth factor (VEGF) are thought to play significant roles in the occurrence and development of MNV. Allograft inflammatory factor-1(AIF-1) is a crucial regulatory factor of vascular tubular structure formation and growth, involving the proliferation and migration of vascular endothelial cells and various tumor cells. This study aimed to understand how AIF-1 effects the proliferation of CECs and the subsequent progression of MNV. To study this, a mouse MNV model was established through laser injury, and the AIF-1 expression levels were then measured using western blot and immunohistochemistry. AIF-1 siRNA was intravitreally injected to silence AIF-1 gene expression. Western blot and choroidal flat mount were performed to measure the progression of MNV and proliferation of the CECs. These results showed that the protein expression of AIF-1 was significantly elevated in the laser-induced mouse MNV model, and the expression trend was consistent with VEGF. The protein level of AIF-1 was significantly decreased after the intravitreal injection of AIF-1 siRNA, the damage range of laser lesions was significantly reduced, and the proliferation of endothelial cells was inhibited. Knockdown of the AIF-1 gene significantly inhibited the expression of mitogen-activated protein kinase p44/42 in MNV lesions. In summary, this research demonstrates that AIF-1 promoted MNV progression by promoting the proliferation of CECs and that silencing AIF-1 significantly ameliorates MNV progression in mouse models, which may act through the p44/42 MAPK signaling pathway. AIF-1 could be a new potential molecular target for MNV.},
}
@article {pmid37079518,
year = {2023},
author = {Kim, S and Stockwell, A and Qin, H and Gao, SS and Sagolla, M and Stoilov, I and Wuster, A and Lai, P and Yaspan, BL and Jeanne, M},
title = {Rare CIDEC coding variants enriched in age-related macular degeneration patients with small low-luminance deficit cause lipid droplet and fat storage defects.},
journal = {PloS one},
volume = {18},
number = {4},
pages = {e0280484},
pmid = {37079518},
issn = {1932-6203},
mesh = {Humans ; Angiogenesis Inhibitors ; Lipid Droplets/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism ; *Vision, Low ; Visual Acuity/genetics ; *Wet Macular Degeneration/metabolism ; },
abstract = {BACKGROUND: The basis of Age-related macular degeneration (AMD) genetic risk has been well documented; however, few studies have looked at genetic biomarkers of disease progression or treatment response within advanced AMD patients. Here we report the first genome-wide analysis of genetic determinants of low-luminance vision deficit (LLD), which is seen as predictive of visual acuity loss and anti-VEGF treatment response in neovascular AMD patients.<br><br>METHODS: AMD patients were separated into small- and large-LLD groups for comparison and whole genome sequencing was performed. Genetic determinants of LLD were assessed by common and rare variant genetic analysis. Follow-up functional analysis of rare coding variants identified by the burden test was then performed in vitro.<br><br>RESULTS: We identified four coding variants in the CIDEC gene. These rare variants were only present in patients with a small LLD, which has been previously shown to indicate better prognosis and better anti-VEGF treatment response. Our in vitro functional characterization of these CIDEC alleles revealed that all decrease the binding affinity between CIDEC and the lipid droplet fusion effectors PLIN1, RAB8A and AS160. The rare CIDEC alleles all cause a hypomorphic defect in lipid droplet fusion and enlargement, resulting in a decreased fat storage capability in adipocytes.<br><br>CONCLUSIONS: As we did not detect CIDEC expression in the ocular tissue affected by AMD, our results suggest that the CIDEC variants do not play a direct role in the eye and influence low-luminance vision deficit via an indirect and systemic effect related to fat storage capacity.},
}
@article {pmid37079325,
year = {2023},
author = {Khateb, S and Chowers, I and Grunin, M},
title = {What Can We Learn From the Surprising Insight Into the Genetic Background of Age-Related Macular Degeneration and Central Serous Chorioretinopathy?.},
journal = {JAMA ophthalmology},
volume = {141},
number = {5},
pages = {457-458},
doi = {10.1001/jamaophthalmol.2023.0927},
pmid = {37079325},
issn = {2168-6173},
mesh = {Humans ; *Central Serous Chorioretinopathy/diagnosis/genetics ; *Macular Degeneration/diagnosis/genetics ; *Choroid Diseases ; Genetic Background ; Tomography, Optical Coherence ; Fluorescein Angiography ; },
}
@article {pmid37079300,
year = {2023},
author = {Rämö, JT and Abner, E and van Dijk, EHC and Wang, X and Brinks, J and Nikopensius, T and Nõukas, M and Marjonen, H and Silander, K and Jukarainen, S and Kiiskinen, T and Choi, SH and Kajanne, R and Mehtonen, J and Palta, P and Lubitz, SA and Kaarniranta, K and Sobrin, L and Kurki, M and Yzer, S and Ellinor, PT and Esko, T and Daly, MJ and den Hollander, AI and Palotie, A and Turunen, JA and Boon, CJF and Rossin, EJ and , and , },
title = {Overlap of Genetic Loci for Central Serous Chorioretinopathy With Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {141},
number = {5},
pages = {449-457},
pmid = {37079300},
issn = {2168-6173},
support = {K12 EY016335/EY/NEI NIH HHS/United States ; R01 HL157635/HL/NHLBI NIH HHS/United States ; R01 HL139731/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Central Serous Chorioretinopathy/diagnosis/genetics/complications ; Genome-Wide Association Study ; Endothelial Cells ; Genetic Loci ; *Macular Degeneration/genetics/complications ; Genetic Background ; },
abstract = {IMPORTANCE: Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases.<br><br>OBJECTIVE: To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD.<br><br>Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in a meta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022.<br><br>MAIN OUTCOMES AND MEASURES: Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by a meta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study.<br><br>RESULTS: A total of 1176 patients with CSC and 526&#x202f;787 controls (312&#x202f;162 female [59.3%]) were included in this analysis: 552 patients with CSC and 343&#x202f;461 controls were identified in the FinnGen study, 103 patients with CSC and 178&#x202f;573&#x2009;controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in a meta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P&#x2009;=&#x2009;.004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P&#x2009;<&#x2009;7.1 &#xd7; 10-20). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95% CI, 0.70-0.83 per +1 SD in AMD-PGS; P&#x2009;=&#x2009;7.4 &#xd7; 10-10). This association may have been mediated by loci containing complement genes.<br><br>CONCLUSIONS AND RELEVANCE: In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.},
}
@article {pmid37078291,
year = {2023},
author = {Tanaka, M and Nakamura, S and Sakaue, T and Yamamoto, T and Maekawa, M and Nishinaka, A and Yasuda, H and Yunoki, K and Sato, Y and Sawa, M and Yoshino, K and Shimazawa, M and Hatano, M and Tokuhisa, T and Higashiyama, S and Hara, H},
title = {BCL6B Contributes to Ocular Vascular Diseases via Notch Signal Silencing.},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
volume = {43},
number = {6},
pages = {927-942},
doi = {10.1161/ATVBAHA.123.318987},
pmid = {37078291},
issn = {1524-4636},
mesh = {Animals ; Humans ; Mice ; *Choroidal Neovascularization/genetics/metabolism ; Endothelial Cells/metabolism ; Macaca fascicularis/metabolism ; *Nucleic Acids/metabolism/therapeutic use ; *Retinal Neovascularization/genetics/metabolism ; Ribose/metabolism/therapeutic use ; *Vascular Diseases/pathology ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {BACKGROUND: Endothelial cell activation is tightly controlled by the balance between VEGF (vascular endothelial cell growth factor) and Notch signaling pathway. VEGF destabilizes blood vessels and promotes neovascularization, which are common features of sight-threatening ocular vascular disorders. Here, we show that BCL6B (B-cell CLL/lymphoma 6 member B protein), also known as BAZF, ZBTB28, and ZNF62, plays a pivotal role in the development of retinal edema and neovascularization.<br><br>METHODS: The pathophysiological physiological role of BCL6B was investigated in cellular and animal models mimicking 2 pathological conditions: retinal vein occlusion and choroidal neovascularization. An in vitro experimental system was used in which human retinal microvascular endothelial cells were supplemented with VEGF. Choroidal neovascularization cynomolgus monkey model was generated to investigate the involvement of BCL6B in the pathogenesis. Mice lacking BCL6B or treated with BCL6B-targeting small-interfering ribose nucleic acid were examined for histological and molecular phenotypes.<br><br>RESULTS: In retinal endothelial cells, the BCL6B expression level was increased by VEGF. BCL6B-deficient endothelial cells showed Notch signal activation and attenuated cord formation via blockage of the VEGF-VEGFR2 signaling pathway. Optical coherence tomography images showed that choroidal neovascularization lesions were decreased by BCL6B-targeting small-interfering ribose nucleic acid. Although BCL6B mRNA expression was significantly increased in the retina, BCL6B-targeting small-interfering ribose nucleic acid suppressed ocular edema in the neuroretina. The increase in proangiogenic cytokines and breakdown of the inner blood-retinal barrier were abrogated in BCL6B knockout (KO) mice via Notch transcriptional activation by CBF1 (C promotor-binding factor 1) and its activator, the NICD (notch intracellular domain). Immunostaining showed that M&#xfc;ller cell activation, a source of VEGF, was diminished in BCL6B-KO retinas.<br><br>CONCLUSIONS: These data indicate that BCL6B may be a novel therapeutic target for ocular vascular diseases characterized by ocular neovascularization and edema.},
}
@article {pmid37078157,
year = {2024},
author = {Gunay, BO},
title = {Evaluation of systemic immune-inflammatory index in patients with wet age-related macular degeneration.},
journal = {Clinical &amp; experimental optometry},
volume = {107},
number = {1},
pages = {47-50},
doi = {10.1080/08164622.2023.2201370},
pmid = {37078157},
issn = {1444-0938},
mesh = {Male ; Female ; Humans ; *Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; *Wet Macular Degeneration ; Tomography, Optical Coherence/methods ; Intravitreal Injections ; Fluorescein Angiography ; },
abstract = {CLINICAL RELEVANCE: The systemic immune-inflammatory index is a relatively new parameter and has been shown to increase in inflammatory diseases.<br><br>BACKGROUND: The primary aim of this study was to investigate the systemic immune-inflammatory index in patients with wet-type age-related macular degeneration. The secondary aim was to determine the relationship between best-corrected visual acuity, central macular thickness, subfoveal choroidal thickness, systemic immune-inflammatory index, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio.<br><br>METHODS: This study retrospectively analysed patients with wet-type age-related macular degeneration between 2018 and 2022. Demographic data and peripheral complete blood count were obtained from the electronic medical record system. The most recent best-corrected visual acuity, central macular thickness, and subfoveal choroidal thickness values (within one month) for complete blood count were obtained from case sheets and the optical coherence tomography digital image database. The systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were calculated. Age- and sex-matched controls were also generated.<br><br>RESULTS: Thirty-three patients (23 males, 10 females) with wet-type age-related macular degeneration and 43 controls (24 males, 19 females) were included. The groups were similar in terms of age and sex (78.0&#x2009;&#xb1;&#x2009;6.3 vs. 75.6&#x2009;&#xb1;&#x2009;6.6&#x2009;years, p&#x2009;=&#x2009;0.59; p&#x2009;=&#x2009;0.38 for sex). The systemic immune-inflammatory index was higher in the wet-type age-related macular degeneration group (460.5 vs. 440.4); however, this difference was not statistically significant. When the correlations between the systemic immune-inflammatory index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, best-corrected visual acuity (logMAR), central macular thickness, and subfoveal choroidal thickness were examined, there was only a moderate positive correlation between best-corrected visual acuity and platelet-to-lymphocyte ratio (r&#x2009;=&#x2009;0.46, p&#x2009;=&#x2009;0.007).<br><br>CONCLUSION: There were no differences in the systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio between the wet-type age-related macular degeneration and control groups. There was a positive correlation between the platelet-to-lymphocyte ratio and best-corrected visual acuity (logMAR). The systemic immune-inflammatory index was higher in patients with wet-type age-related macular degeneration than in the control group; however, this difference was not statistically significant.},
}
@article {pmid37077492,
year = {2023},
author = {Abd Rahman, MH and Amirtharatnam, P and Sharanjeet-Kaur, S and Narayanasamy, S and Mohd Rasdi, HF and Catherine Bastion, ML},
title = {Development of Knowledge, Attitude and Practice Questionnaire for age-related macular degeneration patients.},
journal = {International journal of ophthalmology},
volume = {16},
number = {4},
pages = {589-600},
pmid = {37077492},
issn = {2222-3959},
abstract = {AIM: To develop and validate a questionnaire to evaluate knowledge, attitude and practice of patients diagnosed with age-related macular degeneration (AMD) who have undergone intravitreal injection treatment.<br><br>METHODS: This study was conducted among patients diagnosed with AMD in Kuala Lumpur. The generation of the instrument included four phases which included item and domains development, content, face validity and exploratory factor analysis. Content validity and modified Kappa was used for validation of knowledge domain. Exploratory factor analysis was used for validation of both attitude and practice domains. Face validity was conducted in 12 patients, content validity was ascertained in 120 patients and test-retest reliability was determined in 39 patients with AMD.<br><br>RESULTS: Content validity index (CVI) and modified kappa showed excellent values for most items in the knowledge domain with CVI for item (I-CVI) values between 0.78-1.0 and Kappa values of >0.74. The Kaiser-Meyer-Olkin (KMO) sampling adequacy showed acceptable scores of 0.70 and 0.75 for both attitude and practice domains respectively and Bartlett's Test of sphericity were significant (&#x3c7;[2] =0.00, P<0.001). Factor analysis resulted in five factors with thirty items for attitude domain and four factors with twenty items for practice domain. The Cronbach's alpha showed acceptable values for all items in knowledge, attitude and practice domain with values >0.70 and good test-retest reliability. The final version of the questionnaire consisted of 93 items from four sections consisting of demographic details, knowledge, attitude and practice.<br><br>CONCLUSION: The findings of this validation and reliability study show that the developed questionnaire has a satisfactory psychometric property for measuring KAP of patients diagnosed with AMD undergoing intravitreal injection treatment.},
}
@article {pmid37074695,
year = {2023},
author = {Borrelli, E and Barresi, C and Lari, G and Berni, A and Battista, M and Reibaldi, M and Cascavilla, ML and Bandello, F},
title = {Capturing the Transition From Intermediate to Neovascular AMD: Longitudinal Inner Retinal Thinning and Factors Associated With Neuronal Loss.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {4},
pages = {21},
pmid = {37074695},
issn = {1552-5783},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Choroidal Neovascularization/drug therapy ; Fluorescein Angiography ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Macular Degeneration ; },
abstract = {PURPOSE: To estimate the impact of transition from intermediate to exudative neovascular age-related macular degeneration (AMD) on the inner retina and to assess the relationship of clinical characteristics and optical coherence tomography (OCT) findings with inner retinal changes.<br><br>METHODS: A total of 80 participants (80 eyes) with intermediate AMD at baseline who developed neovascular AMD within 3 months were included in the analysis. OCT scans at follow-up visits (after transition to neovascular AMD) were compared with values at the latest visit with evidence of intermediate AMD to quantify longitudinal inner retinal changes. OCT images were also reviewed for qualitative features reflecting distress of the outer retina or retinal pigment epithelium and for the presence and characteristics of exudation.<br><br>RESULTS: The parafoveal and perifoveal inner retinal thicknesses were 97.6 &#xb1; 12.9 &#xb5;m and 103.5 &#xb1; 16.2 &#xb5;m, respectively, at baseline, and a significant increase in values was detected at the visit with first evidence of neovascular AMD (parafoveal: 99.0 &#xb1; 12.8 &#xb5;m, P = 0.040; perifoveal: 107.9 &#xb1; 19.0 &#xb5;m, P = 0.0007). Conversely, the inner retina was significantly thinner at the 12-month follow-up visit after initiation of the anti-vascular endothelial growth factor therapy (parafoveal: 90.3 &#xb1; 14.8 &#xb5;m, P < 0.0001; perifoveal: 92.0 &#xb1; 21.3 &#xb5;m, P < 0.0001). At the 12-month follow-up visit, OCT evidence of alterations of the external limiting membrane and history of previous intraretinal fluid were associated with a greater inner retinal thinning.<br><br>CONCLUSIONS: The development of exudative neovascularization is associated with significant neuronal loss that may be detected once the exudation is resolved. OCT analysis demonstrated a significant relationship between morphological alterations detected using structural OCT and the amount of inner neuronal loss.},
}
@article {pmid37073550,
year = {2023},
author = {Bartlett, R and Davies, H},
title = {People with dry age-related macular degeneration; views on certification of vision impairment in a primary care setting: An explorative qualitative study.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {43},
number = {4},
pages = {738-751},
doi = {10.1111/opo.13137},
pmid = {37073550},
issn = {1475-1313},
mesh = {Humans ; *Eye Diseases ; *Optometrists ; *Macular Degeneration/diagnosis/therapy ; Primary Health Care ; Certification ; },
abstract = {PURPOSE: Evidence supports the clinical decision-making ability of primary care optometrists with additional qualifications in the identification of eligibility criteria for the certification of vision impairment (CVI). Welsh Government policy is driving pathway change to enable these optometrists to perform CVI. This qualitative study explores the views of people with VI due to dry age-related macular degeneration (AMD) on this pathway change.<br><br>METHODS: Nine people with VI due to dry AMD, attending Macular Society support groups, participated. Individual semi-structured interviews were conducted and analysed concurrently using thematic analysis.<br><br>RESULTS: Five major themes were identified: (1) living with dry AMD, (2) experience of eye care provision, (3) knowledge of CVI, (4) provision of information and (5) CVI in primary care. Participants consistently highlighted the need for the provision of accessible information regarding the certification pathway, dry AMD and the optometrist's role in the provision of eye health care. Information needs to be available prior to the diagnosis of an eye disease, rather than only from the point of diagnosis or where the vision reaches the level required for certification.<br><br>CONCLUSION: The findings support the provision of CVI within primary eye care while highlighting areas of importance in pathway development. These include the provision of accessible information prior to, at the point of and following the diagnosis of an eye condition. Information provided needs to extend to the awareness of the role of the optometrist in the provision of eye care, and public health awareness of modifiable risk factors, which will influence the possibility of disease development in later life. The findings provide information that will be useful to those responsible for the provision of CVI within primary care.},
}
@article {pmid37072329,
year = {2023},
author = {Muraleva, NA and Kolosova, NG},
title = {Alteration of the MEK1/2-ERK1/2 Signaling Pathway in the Retina Associated with Age and Development of AMD-Like Retinopathy.},
journal = {Biochemistry. Biokhimiia},
volume = {88},
number = {2},
pages = {179-188},
doi = {10.1134/S0006297923020025},
pmid = {37072329},
issn = {1608-3040},
mesh = {Rats ; Animals ; Rats, Wistar ; MAP Kinase Signaling System ; *Neurodegenerative Diseases/metabolism ; Retina/metabolism ; *Macular Degeneration/metabolism ; *Retinal Diseases/metabolism/pathology ; Signal Transduction ; },
abstract = {Age-related macular degeneration (AMD) is a complex neurodegenerative disease and a major cause of irreversible visual impairment in patients in developed countries. Although age is the greatest risk factor in AMD, molecular mechanisms involved in AMD remain unknown. Growing evidence shows that dysregulation of MAPK signaling contributes to aging and neurodegenerative diseases; however, the information on the role of MAPK upregulation in these processes is controversial. ERK1 and ERK2 participate in the maintenance of proteostasis through the regulation of protein aggregation induced by the endoplasmic reticulum stress and other stress-mediated cell responses. To assess the contribution of alterations in the ERK1/2 signaling to the AMD development, we compared age-associated changes in the activity of ERK1/2 signaling pathway in the retina of Wistar rats (control) and OXYS rats that develop AMD-like retinopathy spontaneously. The activity of the ERK1/2 signaling increased during physiological aging in the retina of Wistar rats. The manifestation and progression of the AMD-like pathology in the retina of OXYS rats was accompanied by hyperphosphorylation of ERK1/2 and MEK1/2, the key kinases of the ERK1/2 signaling pathway. The progression of the AMD-like pathology was also associated with the ERK1/2-dependent tau protein hyperphosphorylation and increase in the ERK1/2-dependent phosphorylation of alpha B crystallin at Ser45 in the retina.},
}
@article {pmid37071417,
year = {2023},
author = {Thines, L and Roushar, FJ and Hedman, AC and Sacks, DB},
title = {The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling.},
journal = {The Journal of cell biology},
volume = {222},
number = {6},
pages = {},
pmid = {37071417},
issn = {1540-8140},
mesh = {Humans ; *ras GTPase-Activating Proteins/genetics/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, G-Protein-Coupled/metabolism ; *Signal Transduction ; },
abstract = {The scaffold protein IQGAP1 assembles multiprotein signaling complexes to influence biological functions. Cell surface receptors, particularly receptor tyrosine kinases and G-protein coupled receptors, are common IQGAP1 binding partners. Interactions with IQGAP1 modulate receptor expression, activation, and/or trafficking. Moreover, IQGAP1 couples extracellular stimuli to intracellular outcomes via scaffolding of signaling proteins downstream of activated receptors, including mitogen-activated protein kinases, constituents of the phosphatidylinositol 3-kinase pathway, small GTPases, and β-arrestins. Reciprocally, some receptors influence IQGAP1 expression, subcellular localization, binding properties, and post-translational modifications. Importantly, the receptor:IQGAP1 crosstalk has pathological implications ranging from diabetes and macular degeneration to carcinogenesis. Here, we describe the interactions of IQGAP1 with receptors, summarize how they modulate signaling, and discuss their contribution to pathology. We also address the emerging functions in receptor signaling of IQGAP2 and IQGAP3, the other human IQGAP proteins. Overall, this review emphasizes the fundamental roles of IQGAPs in coupling activated receptors to cellular homeostasis.},
}
@article {pmid37070437,
year = {2023},
author = {Mittal, R and Sharma, S and Mittal, A and Mittal, A},
title = {Recent Progress in Selective COX-2 Inhibitor Formulations and Therapeutic Applications - A Patent Review (2012-2022).},
journal = {Mini reviews in medicinal chemistry},
volume = {23},
number = {22},
pages = {2130-2141},
doi = {10.2174/1389557523666230417102123},
pmid = {37070437},
issn = {1875-5607},
abstract = {INTRODUCTION: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX- 2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use.<br><br>METHODS: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects.<br><br>CONCLUSION: Emphasis has been given on the formulation, drug combination, administration routesmodification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.},
}
@article {pmid37069537,
year = {2023},
author = {Nassisi, M and Pozzo Giuffrida, F and Milella, P and Ganci, S and Aretti, A and Mainetti, C and Dell'Arti, L and Mapelli, C and Viola, F},
title = {Delaying anti-VEGF therapy during the COVID-19 pandemic: long-term impact on visual outcomes in patients with neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {156},
pmid = {37069537},
issn = {1471-2415},
mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Angiogenesis Inhibitors/therapeutic use ; Communicable Disease Control ; *COVID-19 ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Pandemics ; Ranibizumab/therapeutic use ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy ; Male ; },
abstract = {OBJECTIVES: To evaluate the outcomes of delayed intravitreal injections (IVIs) caused by the outbreak of coronavirus disease 2019 (COVID-19), in patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: nAMD patients with scheduled IVIs between March 1[st] and April 30[th], 2020 were stratified through a risk-based selection into a non-adherent group (NA-group) if they skipped at least one IVI and an adherent group (A-group) if they followed their treatment schedule. During the pandemic visit (v[0]), if a significant worsening of the disease was detected, a rescue therapy of three-monthly IVIs was performed. Multimodal imaging and best-corrected visual acuity (BCVA) findings were evaluated after 6&#xa0;months (v[6]), compared between groups and with the visit prior the lockdown (v[-1]).<br><br>RESULTS: Two hundred fifteen patients (132 females, mean age: 81.89&#x2009;&#xb1;&#x2009;5.98&#xa0;years) delayed their scheduled IVI while 83 (53 females, mean age: 77.92&#x2009;&#xb1;&#x2009;6.06&#xa0;years) adhered to their protocol. For both groups, BCVA at v[0] was significantly worse than v[-1] (mean 4.15&#x2009;&#xb1;&#x2009;7.24 ETDRS letters reduction for the NA-group and 3&#x2009;&#xb1;&#x2009;7.96 for the A-group) but remained stable at v[6]. The two groups did not significantly differ in BCVA trends after 6&#xa0;months and neither for development of atrophy nor fibrosis.<br><br>CONCLUSIONS: A risk-based selection strategy and a rescue therapy may limit the long-term outcomes of an interruption of the treatment protocol in patients with nAMD.},
}
@article {pmid37069516,
year = {2023},
author = {Li, Y and Li, J and Pan, X and Zhang, Z and Zheng, Y},
title = {Management of angle-closure glaucoma with X-linked retinoschisis: a case report.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {159},
pmid = {37069516},
issn = {1471-2415},
mesh = {Male ; Humans ; Adult ; *Glaucoma, Angle-Closure/complications/genetics/surgery ; *Retinoschisis/diagnosis/genetics/surgery ; Lens Implantation, Intraocular/adverse effects ; *Glaucoma/surgery ; *Cataract Extraction ; Intraocular Pressure ; *Phacoemulsification ; },
abstract = {BACKGROUND: X-linked retinoschisis (XLRS), due to mutations in the RS1 gene, is a common genetically determined form of macular degeneration. This report describes an unusual case of angle-closure glaucoma (ACG) with XLRS and discusses the treatment.<br><br>CASE PRESENTATION: A 39-year-old Chinese man with an X chromosome-recessive inherited c.489G&#x2009;>&#x2009;A variant in the RS1 gene was diagnosed as XLRS and ACG, presenting with cystic macular lesions, shallow anterior chamber depth (ACD), and angle-closure with uncontrolled intraocular pressure (IOP). Malignant glaucoma occurred following trabeculectomy combining phacoemulsification with intraocular lens (IOL) implantation and goniosynechialysis. Subsequent anterior vitrectomy and irido-zonulo-hyaloid-vitrectomy (IZHV) effectively lowered IOP and deepened ACD, but the cystic cavity became larger.<br><br>CONCLUSIONS: There is a potential risk of malignant glaucoma in ACG patients with XLRS after filtering surgery. Although anterior vitrectomy can effectively resolve aqueous misdirection, the macular retinoschisis may get worse. Awareness of this risk may aid in surgical planning and postoperative management in these patients.},
}
@article {pmid37071922,
year = {2024},
author = {Ramtohul, P and Freund, KB},
title = {LONG-TERM PRESERVATION OF VISUAL ACUITY AFTER RESORPTION OF ACQUIRED VITELLIFORM LESIONS IN AGE-RELATED MACULAR DEGENERATION.},
journal = {Retinal cases &amp; brief reports},
volume = {18},
number = {4},
pages = {417-420},
pmid = {37071922},
issn = {1937-1578},
mesh = {Humans ; Male ; Middle Aged ; *Visual Acuity/physiology ; *Fluorescein Angiography/methods ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Macular Degeneration/diagnosis ; Fundus Oculi ; Follow-Up Studies ; Vitelliform Macular Dystrophy/diagnosis/complications ; Time Factors ; },
abstract = {PURPOSE: To report the long-term (23 years) clinical and multimodal imaging features of acquired vitelliform lesions (AVLs) associated with nonneovascular age-related macular degeneration.<br><br>METHODS: Retrospective case report. Color and red-free fundus photographs, high-resolution optical coherence tomography, fluorescein and indocyanine green angiography, and optical coherence tomography-angiography were performed.<br><br>RESULTS: A 58-year-old man presented with bilateral AVLs in the setting of nonneovascular age-related macular degeneration. At baseline, his best-corrected visual acuity was 20/30 in his right eye and 20/20 in his left eye. Red-free fundus photographs showed AVLs with cuticular drusen in both eyes corresponding to a "stars-in-the-sky" pattern on fluorescein. Indocyanine green angiography showed no evidence of macular neovascularization. Throughout the 23-year follow-up, the patient reported consuming 20 mg/day of lutein supplement. At the end of follow-up, his best-corrected visual acuity was 20/20 in both eyes. Color fundus photographs showed resorption of the AVLs in both eyes and High-Res optical coherence tomography showed relative preservation of the outer retinal bands in the fovea. Optical coherence tomography-angiography confirmed the absence of macular neovascularization.<br><br>CONCLUSION: In nonneovascular age-related macular degeneration, spontaneous resorption of AVLs may be associated with long-term maintenance of visual acuity and relative preservation of the outer retinal morphology.},
}
@article {pmid37067634,
year = {2023},
author = {Matoba, R and Morimoto, N and Kawasaki, R and Fujiwara, M and Kanenaga, K and Yamashita, H and Sakamoto, T and Morizane, Y},
title = {A nationwide survey of newly certified visually impaired individuals in Japan for the fiscal year 2019: impact of the revision of criteria for visual impairment certification.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {3},
pages = {346-352},
pmid = {37067634},
issn = {1613-2246},
mesh = {Adolescent ; Aged, 80 and over ; Humans ; Blindness/etiology ; Certification ; Cross-Sectional Studies ; *Glaucoma/diagnosis/epidemiology/complications ; Japan/epidemiology ; *Vision, Low/epidemiology ; *Persons with Visual Disabilities ; },
abstract = {PURPOSE: To determine the status of visual impairment certification in Japan in the fiscal year 2019 and the impact of revising the criteria for visual impairment certification implemented in 2018.<br><br>STUDY DESIGN: Observational cross-sectional study.<br><br>METHODS: We requested welfare offices throughout Japan to submit data of age, sex, causative diseases, and visual impairment grades for newly certified visually impaired individuals aged&#x2009;&#x2265;&#x2009;18 years during the fiscal year 2019. The certification was based on criteria of the Act on Welfare of Physically Disabled Persons.<br><br>RESULTS: Altogether, data were collected for 16,504 newly certified visually impaired individuals. The most common age group was 80-89 years (29.6%), followed by 70-79 (28.2%) and 60-69 (15.3%) years. The most common causative disease was glaucoma (40.7%), followed by retinitis pigmentosa (13.0%), diabetic retinopathy (10.2%), and macular degeneration (9.1%). The most common impairment grade was grade 2 (40.8%), followed by 5 (21.2%) and 1 (17.0%). Compared to the fiscal year 2015, there was a considerable increase in the number of individuals certified with glaucoma in the fiscal year 2019. Moreover, there was a significant increase in the number of individuals with certified grades 1 and 2 visual impairment, with a decrease in the number of individuals with certified grade 6 visual impairment.<br><br>CONCLUSION: The changes revealed in this study were primarily due to the revised certification criteria implemented in July 2018, indicating that it is important to review the certification criteria and to repeat surveys similar to the present study.},
}
@article {pmid37065847,
year = {2023},
author = {Rohowetz, LJ and Koulen, P},
title = {Stem cell-derived retinal pigment epithelium cell therapy: Past and future directions.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1098406},
pmid = {37065847},
issn = {2296-634X},
support = {R01 EY030747/EY/NEI NIH HHS/United States ; },
abstract = {The eyes are relatively immune privileged organs, making them ideal targets for stem cell therapy. Researchers have recently developed and described straightforward protocols for differentiating embryonic and induced pluripotent stem cells into retinal pigment epithelium (RPE), making diseases affecting the RPE, such as age-related macular degeneration (AMD), viable targets for stem cell therapy. With the advent of optical coherence tomography, microperimetry, and various other diagnostic technologies, the ability to document disease progression and monitor response to treatments such as stem cell therapy has been significantly enhanced in recent years. Previous phase I/II clinical trials have employed various cell origins, transplant methods, and surgical techniques to identify safe and efficacious methods of RPE transplantation, and many more are currently underway. Indeed, findings from these studies have been promising and future carefully devised clinical trials will continue to enhance our understanding of the most effective methods of RPE-based stem cell therapy, with the hope to eventually identify treatments for disabling and currently incurable retinal diseases. The purpose of this review is to briefly outline existing outcomes from initial clinical trials, review recent developments, and discuss future directions of clinical research involving stem-cell derived RPE cell transplantation for retinal disease.},
}
@article {pmid37065488,
year = {2023},
author = {Benavides-Aguilar, JA and Morales-Rodríguez, JI and Ambriz-González, H and Ruiz-Manriquez, LM and Banerjee, A and Pathak, S and Duttaroy, AK and Paul, S},
title = {The regulatory role of microRNAs in common eye diseases: A brief review.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1152110},
pmid = {37065488},
issn = {1664-8021},
abstract = {MicroRNAs (miRNAs) are highly conserved, small non-coding RNA molecules (∼21 nucleotides) that regulate numerous biological processes, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation, and proliferation either by mRNA degradation or translation repression. Since eye physiology requires a perfect orchestration of complex regulatory networks, an altered expression of key regulatory molecules such as miRNAs potentially leads to numerous eye disorders. In recent years, comprehensive progress has been made in demonstrating the precise roles of miRNAs, emphasizing their potential use in diagnostic and therapeutic purposes of chronic human diseases. Thus, this review explicitly illustrates the regulatory roles of miRNAs in four common eye disorders, such as cataract, glaucoma, macular degeneration, and uveitis, and their application in disease management.},
}
@article {pmid37065470,
year = {2023},
author = {Zhou, X and Zhang, J and Ding, Y and Huang, H and Li, Y and Chen, W},
title = {Predicting late-stage age-related macular degeneration by integrating marginally weak SNPs in GWA studies.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1075824},
pmid = {37065470},
issn = {1664-8021},
support = {R01 EB034116/EB/NIBIB NIH HHS/United States ; R01 GM141076/GM/NIGMS NIH HHS/United States ; R21 EY030488/EY/NEI NIH HHS/United States ; S10 OD028483/OD/NIH HHS/United States ; },
abstract = {Introduction: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease and the leading cause of blindness in developed countries. Current genome-wide association studies (GWAS) for late-stage age-related macular degeneration are mainly single-marker-based approaches, which investigate one Single-Nucleotide Polymorphism (SNP) at a time and postpone the integration of inter-marker Linkage-disequilibrium (LD) information in the downstream fine mappings. Recent studies showed that directly incorporating inter-marker connection/correlation into variants detection can help discover novel marginally weak single-nucleotide polymorphisms, which are often missed in conventional genome-wide association studies, and can also help improve disease prediction accuracy. Methods: Single-marker analysis is performed first to detect marginally strong single-nucleotide polymorphisms. Then the whole-genome linkage-disequilibrium spectrum is explored and used to search for high-linkage-disequilibrium connected single-nucleotide polymorphism clusters for each strong single-nucleotide polymorphism detected. Marginally weak single-nucleotide polymorphisms are selected via a joint linear discriminant model with the detected single-nucleotide polymorphism clusters. Prediction is made based on the selected strong and weak single-nucleotide polymorphisms. Results: Several previously identified late-stage age-related macular degeneration susceptibility genes, for example, BTBD16, C3, CFH, CFHR3, HTARA1, are confirmed. Novel genes DENND1B, PLK5, ARHGAP45, and BAG6 are discovered as marginally weak signals. Overall prediction accuracy of 76.8% and 73.2% was achieved with and without the inclusion of the identified marginally weak signals, respectively. Conclusion: Marginally weak single-nucleotide polymorphisms, detected from integrating inter-marker linkage-disequilibrium information, may have strong predictive effects on age-related macular degeneration. Detecting and integrating such marginally weak signals can help with a better understanding of the underlying disease-development mechanisms for age-related macular degeneration and more accurate prognostics.},
}
@article {pmid37064960,
year = {2023},
author = {Chakraborty, D and Mondal, S and Boral, S and Das, A and Sinha, TK and Majumdar, S and Bhattacharya, R and Maitra, R},
title = {Biosimilar versus InnovAtor MoLecule of RAnibizumab in Neovascular Age-Related MaCular DEgeneration (The BALANCE Trial): Real-World Evidence.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1067-1076},
pmid = {37064960},
issn = {1177-5467},
abstract = {PURPOSE: To analyse outcomes of innovator ranibizumab (IRM) (Lucentis) and biosimilar ranibizumab (BRM) (Razumab) in Indian eyes with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Retrospective observational study in nAMD patients, who were treated with IRM or BRM (3 loading doses followed by pro re nata (PRN). Primary outcome measures were change in best corrected visual acuity (BCVA) and central macular thickness (CMT) along with safety analysis. Secondary outcomes measures were changes in the subretinal fluid (SRF) and intraretinal fluid (IRF).<br><br>RESULTS: Inclusion criteria were satisfied in 164 eyes (60.74%). A total of 87 eyes were treated with IRM, and 77 eyes received BRM. Baseline BCVA was 0.57&#xb1;0.27 logMAR in IRM group and 0.61&#xb1;0.25 in the BRM group. At 3, 6, 9, and 12 months BCVA was 0.27&#xb1;0.22 (p<0.0001), 0.34&#xb1;0.23 (p<0.0001), 0.39&#xb1;0.25 (p<0.0001), and 12 months 0.41&#xb1;0.23 (p<0.0001) in the IRM group and 0.24&#xb1;0.16 (p<0.0001), 0.27&#xb1;0.16 (p<0.0001), 0.34&#xb1;0.17 (p<0.0001), 0.38&#xb1;0.18 (p<0.0001) in the BRM group. Baseline CMT was 420.39&#xb1;54.45 &#x3bc;m in IRM group and 407.82&#xb1;53.07 &#x3bc;m in BRM group. At 3, 6, 9, and 12 months, CMT decreased to 258.28&#xb1;20.4 &#x3bc;m (p<0.0001), 268.38&#xb1;19.5 &#x3bc;m (p<0.0001), 269.51&#xb1;32.41 &#x3bc;m (p<0.0001), and 278.28&#xb1;16.56 &#x3bc;m (p<0.0001) in the IRM group and 258.84&#xb1;17.47 &#x3bc;m (p<0.0001), 265.69&#xb1;17.29 &#x3bc;m (p<0.0001), 273.64&#xb1;23.13 &#x3bc;m (p<0.0001), and 283.09&#xb1;19.66 &#x3bc;m (p<0.0001) in the BRM group. Similar improvements in IRF and SRF levels in the patients were noted in both groups. Required number of doses of IRM and BRM was similar over the 12 month period in both groups. A similar profile of adverse events was noted in both the groups.<br><br>CONCLUSION: Intravitreal injection of IRM and BRM show similar efficacy and safety in Indian eyes with nAMD.},
}
@article {pmid37064958,
year = {2023},
author = {Van Cleemput, L and Peeters, F and Jacob, J},
title = {Brolucizumab for Neovascular Age-Related Macular Degeneration (BEL Study).},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {1077-1085},
pmid = {37064958},
issn = {1177-5467},
abstract = {PURPOSE: This retrospective observational study reports early results on a cohort of neovascular age-related macular degeneration (nAMD) patients switched to brolucizumab, a recently approved anti-vascular endothelial growth factor (anti-VEGF).<br><br>PATIENTS AND METHODS: We evaluated best-corrected visual acuity (BCVA), treatment interval, central subfield retinal thickness (CST) and the presence of intra-retinal (IRF), subretinal (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid on optical coherence tomography (OCT). Concurrently, patients were carefully examined for signs of intra-ocular inflammation (IOI) and other adverse events.<br><br>RESULTS: Seventeen patients (19 eyes) were included. The difference in BCVA at baseline compared to the last examination following brolucizumab injection was not statistically significant (Wilcoxon signed-rank test, p=0.247). Mean CST decrease was -5.16 &#xb1;48.28 &#xb5;m (p=0.647). A morphological improvement in IRF was observed in four eyes, with a complete resolution in 50% (n=2) and a decrease in 50% (n=2). Regarding SRF (total n=15), resolution was seen in 46.67% (n=7), decrease in 26.67% (n=4) and stabilization in 13.33% (n=2). Increase in SRF was observed in 13.33% (n=2). Of 14 eyes with sub-RPE fluid, 7.14% (n=1) demonstrated a resolution, 42.86% (n=6) a decrease, 50% (n=7) a stabilization and none an increase in fluid. Mean treatment interval was increased by 4.08 &#xb1;1.40 weeks (p<0.001). Treatment was discontinued in seven eyes (41.18%), including four cases due to IOI. In all four cases, inflammation was mild and resolved under corticosteroid treatment. No cases of vasculitis were observed.<br><br>CONCLUSION: This study provides additional data suggesting that brolucizumab is a beneficial alternative for patients refractory to other anti-VEGF therapies. It can provide a morphological reduction in fluid and prolong the treatment interval, while maintaining a stable BCVA and CST. However, as a higher occurrence of IOI is probable, patients should be informed, selected and monitored carefully. Signs of inflammation should be detected early and treated promptly.},
}
@article {pmid37062710,
year = {2023},
author = {Lynch, AM and McReynolds, AJ and Wittel, RJ and Mathias, MT and Manoharan, N and Emerick, LM and Brocious, ML and Patnaik, JL and , },
title = {The use of social and digital media to recruit patients with early and intermediate age-related macular degeneration.},
journal = {Clinical &amp; experimental ophthalmology},
volume = {51},
number = {4},
pages = {398-401},
pmid = {37062710},
issn = {1442-9071},
support = {R01 EY032456/EY/NEI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Internet ; *Macular Degeneration/diagnosis ; Visual Acuity ; },
}
@article {pmid37058103,
year = {2023},
author = {Wang, J and Hormel, TT and Tsuboi, K and Wang, X and Ding, X and Peng, X and Huang, D and Bailey, ST and Jia, Y},
title = {Deep Learning for Diagnosing and Segmenting Choroidal Neovascularization in OCT Angiography in a Large Real-World Data Set.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {4},
pages = {15},
pmid = {37058103},
issn = {2164-2591},
support = {R01 EY024544/EY/NEI NIH HHS/United States ; R01 EY027833/EY/NEI NIH HHS/United States ; P30 EY010572/EY/NEI NIH HHS/United States ; T32 EY023211/EY/NEI NIH HHS/United States ; UL1 TR002369/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; *Deep Learning ; *Choroidal Neovascularization/diagnostic imaging/drug therapy ; *Macula Lutea ; },
abstract = {PURPOSE: To diagnose and segment choroidal neovascularization (CNV) in a real-world multicenter clinical OCT angiography (OCTA) data set using deep learning.<br><br>METHODS: A total of 105,66 OCTA scans from 3135 eyes, including 4701 with CNV and 5865 without, were collected in five eye clinics. Both 3 &#xd7; 3-mm and 6 &#xd7; 6-mm scans of the central and temporal macula were included. Scans with CNV were collected from multiple diseases, and scans without CNV were collected from both healthy controls and those with multiple diseases. No scans were removed during training or testing due to poor quality. The trained hybrid multitask convolutional neural network outputs a CNV diagnosis and membrane segmentation, respectively.<br><br>RESULTS: The model demonstrated a highly accurate CNV diagnosis (area under receiver operating characteristic curve = 0.97), achieving a sensitivity of 95% at 95% specificity. The model also correctly segmented CNV lesions (F1 score = 0.78 &#xb1; 0.19). Additionally, model performance was comparable on both high-definition 3 &#xd7; 3-mm scans and low-definition 6 &#xd7; 6-mm scans. The model did not suffer large performance variations under different diseases. We also show that a subclinical lesion in a patient with neovascular age-related macular degeneration can be monitored over a multiyear time frame using our approach.<br><br>CONCLUSIONS: The proposed method can accurately diagnose and segment CNV in a large real-world clinical data set.<br><br>TRANSLATIONAL RELEVANCE: The algorithm could enable automated CNV screening and quantification in the clinic, which will help improve CNV diagnosis and treatment evaluation.},
}
@article {pmid37056999,
year = {2023},
author = {Ji, Y and Ji, Y and Liu, Y and Zhao, Y and Zhang, L},
title = {Research progress on diagnosing retinal vascular diseases based on artificial intelligence and fundus images.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1168327},
pmid = {37056999},
issn = {2296-634X},
abstract = {As the only blood vessels that can directly be seen in the whole body, pathological changes in retinal vessels are related to the metabolic state of the whole body and many systems, which seriously affect the vision and quality of life of patients. Timely diagnosis and treatment are key to improving vision prognosis. In recent years, with the rapid development of artificial intelligence, the application of artificial intelligence in ophthalmology has become increasingly extensive and in-depth, especially in the field of retinal vascular diseases. Research study results based on artificial intelligence and fundus images are remarkable and provides a great possibility for early diagnosis and treatment. This paper reviews the recent research progress on artificial intelligence in retinal vascular diseases (including diabetic retinopathy, hypertensive retinopathy, retinal vein occlusion, retinopathy of prematurity, and age-related macular degeneration). The limitations and challenges of the research process are also discussed.},
}
@article {pmid37056731,
year = {2023},
author = {Ahn, SJ},
title = {Editorial: Molecular imaging in retinal diseases.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1180330},
pmid = {37056731},
issn = {2296-858X},
}
@article {pmid37056542,
year = {2023},
author = {Abusharkh, FH and Kurdi, L and Shigdar, RW and Mandura, RA and Alattas, K},
title = {Prevalence and Associated Risk Factors of Age-Related Macular Degeneration in the Retina Clinic at a Tertiary Center in Makkah Province, Saudi Arabia: A Retrospective Record Review.},
journal = {Cureus},
volume = {15},
number = {3},
pages = {e36048},
pmid = {37056542},
issn = {2168-8184},
abstract = {Background Age-related macular degeneration (AMD) is a progressive disease involving the macular region of the retina and is considered a significant cause of vision loss worldwide. With the increase in life expectancy in various countries, this problem has become more apparent. We retrospectively evaluated the prevalence of AMD among patients visiting the retina clinic at King Abdulaziz University Hospital (Jeddah, Makkah Province, Saudi Arabia) to identify the commonly associated risk factors of AMD. Methods The records of 3,067 individuals from 2017 to 2021 were reviewed. Of these, 1,935 were enrolled in the study. Results The prevalence of AMD among the patients was 4%. Regarding non-modifiable risk factors, age and having a family history of AMD showed a significant association (p = 0.001 and 0.043, respectively). However, sex and nationality were not significantly associated. As for modifiable risk factors, smoking and hypertension demonstrated a significant relationship (p < 0.001 and p = 0.002, respectively). However, the association with diabetes mellitus and dyslipidemia was not significant. Conclusion Our study shows that AMD is widely prevalent in Saudi Arabia and is associated with age, family history, smoking, and hypertension. Therefore, patients at risk of AMD must be screened and managed promptly before disease progression.},
}
@article {pmid37056126,
year = {2023},
author = {Maurya, M and Bora, K and Blomfield, AK and Pavlovich, MC and Huang, S and Liu, CH and Chen, J},
title = {Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.},
journal = {Neural regeneration research},
volume = {18},
number = {10},
pages = {2173-2181},
pmid = {37056126},
issn = {1673-5374},
support = {R01 EY024963/EY/NEI NIH HHS/United States ; R01 EY028100/EY/NEI NIH HHS/United States ; R01 EY031765/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration; however, effective treatment is not yet available for geographical atrophy in dry age-related macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human age-related macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.},
}
@article {pmid37056108,
year = {2023},
author = {Oderinlo, O and Bogunjoko, T and Hassan, AO and Idris, O and Dalley, A and Oshunkoya, L and Odubela, T},
title = {Normal central foveal thickness in a thousand eyes of healthy patients in sub Saharan Africa using fourier domain optical coherence tomography.},
journal = {Nigerian journal of clinical practice},
volume = {26},
number = {3},
pages = {331-335},
doi = {10.4103/njcp.njcp_318_22},
pmid = {37056108},
issn = {1119-3077},
mesh = {Male ; Female ; Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Retina ; Fovea Centralis/diagnostic imaging ; Africa South of the Sahara ; },
abstract = {BACKGROUND: Optical coherence tomography provides high resolution in vivo images of the retina which are essential for diagnosis and follow up of patients with retina disorders like macula edema and exudative age-related macular degeneration. Establishing the normal range of central fovea values in our population provides vital baseline data for comparison.<br><br>AIM: To report the range of normal central fovea thickness measurements in eyes of healthy hospital patients in sub-Saharan Africa using a commercially available Fourier domain optical coherence tomography (OCT) scan.<br><br>PATIENTS AND METHODS: A retrospective non-comparative review of case files of a thousand consecutive healthy patients who had retina OCT scans between January 2015 and December 2019 was done.<br><br>RESULTS: Data from 1000 consecutive eyes of 500 healthy patients were used for the study. There were 181 females and 319 males. The mean central foveal thickness was 239.48 microns (&#x3bc;m), with a minimum thickness of 200.0 &#x3bc;m and maximum thickness of 297.0 &#x3bc;m. Males had significantly (P < 0.001) thicker mean CFT (mean CFT = 241.77 &#x3bc;m) compared with females (mean CFT = 235.43 &#x3bc;m). The mean CFT increased with age of participants by 0.139 &#x3bc;m (P < 0.001) for every year of life below 70.<br><br>CONCLUSION: The mean central foveal thickness (CFT) in eyes of healthy patients in our study was 239.48 &#x3bc;m with a range from 200 &#x3bc;m to 297.0 &#x3bc;m. Males had thicker mean CFT compared with females and there was a significant increase in mean CFT by 0.139 &#x3bc;m (P < 0.001) for every year of life below 70.},
}
@article {pmid37055868,
year = {2023},
author = {Silva Tavares Neto, JED and Cyrino, FVR and Lucena, MM and Scott, IU and Messias, AMV and Jorge, R},
title = {Intravitreal bevacizumab plus propranolol for neovascular age-related macular degeneration (the BEVALOL study): a phase I clinical trial.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {28},
pmid = {37055868},
issn = {2056-9920},
support = {302946/2019//CNPq/ ; },
abstract = {BACKGROUND: Given the persistently large public health impact of neovascular age-related macular degeneration (nARMD) despite many years of anti-VEGF therapy as the first-line treatment and the demonstrated ability of b-blockers to reduce neovascularization, a synergistic effect between an anti-VEGF agent and an intravitreal beta-blocker is important to investigate in the quest for therapeutic alternatives that maximize efficacy and/or reduce costs. The main purpose of this study is to investigate the safety of a 0.1 ml intravitreal injection of a combination of bevacizumab (1.25 mg/0.05 ml) and propranolol (50 g/0.05 ml) to treat nARMD.<br><br>METHODS: Prospective phase I clinical trial that included patients with nARMD. Comprehensive ophthalmic evaluation was performed at baseline and included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), biomicroscopy of the anterior and posterior segments, binocular indirect ophthalmoscopy, color fundus photography, spectral&#xa0;domain optical coherence tomography (OCT), OCT angiography (OCT-A), fluorescein angiography (Spectralis, Heidelberg), and full-field electroretinography (ERG). All eyes were treated with a 0.1&#xa0;ml intravitreal injection of a combination of bevacizumab (1.25&#xa0;mg/0.05&#xa0;ml) and propranolol (50&#xa0;g/0.05&#xa0;ml) within 1&#xa0;week of baseline evaluation. The patients were reexamined at weeks 4, 8 and 12, and clinical evaluation and SD-OCT were performed at all follow-up visits. Additional injections of combination bevacizumab (1.25&#xa0;mg/0.05&#xa0;ml) and propranolol (50&#xa0;g/0.05&#xa0;ml) were administered at weeks 4 and 8. At the final study evaluation (week 12), color fundus photography, OCT-A, fluorescein angiography, and full-field ERG were repeated.<br><br>RESULTS: Eleven patients (11 eyes) completed all study visits of the 12&#xa0;week study. Full field ERG b-waves did not show significant (p&#x2009;<&#x2009;0.05) changes at week 12 compared to baseline. During the 12&#xa0;week follow-up period, none of the study eyes developed intraocular inflammation, endophthalmitis or intraocular pressure elevation more than 4&#xa0;mmHg over baseline. Mean&#x2009;&#xb1;&#x2009;SE BCVA (logMAR) was 0.79&#x2009;&#xb1;&#x2009;0.09 at baseline and was significantly (p&#x2009;<&#x2009;0.05) improved to 0.61&#x2009;&#xb1;&#x2009;0.10 at week 4; 0.53&#x2009;&#xb1;&#x2009;0.10 at week 8; and 0.51&#x2009;&#xb1;&#x2009;0.09 at week 12. Mean&#x2009;&#xb1;&#x2009;SE central subfield thickness (CST) (&#x3bc;m) was 462&#x2009;&#xb1;&#x2009;45 at baseline and was significantly (p&#x2009;<&#x2009;0.05) lower at 4, 8 and 12&#xa0;weeks (385&#x2009;&#xb1;&#x2009;37; 356&#x2009;&#xb1;&#x2009;29 and 341&#x2009;&#xb1;&#x2009;24, respectively).<br><br>CONCLUSIONS: In this 12&#xa0;week trial of a combination of intravitreal bevacizumab and propranolol for treatment of nARMD, no adverse events or signals of ocular toxicity were observed. Further studies using this combination therapy are warranted. Trial Registration Project registered in Plataforma Brasil with CAAE number 28108920.0.0000.5440 and approved in ethics committee of Clinics Hospital of Ribeirao Preto Medicine School of S&#xe3;o Paulo University-Ribeir&#xe3;o Preto, S&#xe3;o Paulo, Brazil (appreciation number 3.999.989 gave the approval).},
}
@article {pmid37055258,
year = {2023},
author = {Clark, R and Lee, SS and Du, R and Wang, Y and Kneepkens, SCM and Charng, J and Huang, Y and Hunter, ML and Jiang, C and Tideman, JWL and Melles, RB and Klaver, CCW and Mackey, DA and Williams, C and Choquet, H and Ohno-Matsui, K and Guggenheim, JA and , and , },
title = {A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration.},
journal = {EBioMedicine},
volume = {91},
number = {},
pages = {104551},
pmid = {37055258},
issn = {2352-3964},
support = {MC_UU_00007/10/MRC_/Medical Research Council/United Kingdom ; MR/T033371/1/MRC_/Medical Research Council/United Kingdom ; R01 EY027004/EY/NEI NIH HHS/United States ; MC_PC_15018/MRC_/Medical Research Council/United Kingdom ; R01 EY033010/EY/NEI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; G9815508/MRC_/Medical Research Council/United Kingdom ; MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; RC2 AG036607/AG/NIA NIH HHS/United States ; MC_PC_19009/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adult ; Child ; Humans ; Asian People/genetics ; Ethnicity ; Genome-Wide Association Study ; *Macular Degeneration/diagnosis/genetics/epidemiology ; *Myopia/diagnosis/genetics ; European People ; African People ; South Asian People ; East Asian People ; },
abstract = {BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER.<br><br>METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression.<br><br>FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR&#xa0;=&#xa0;1.07 (0.92-1.24).<br><br>INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for.<br><br>FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).},
}
@article {pmid37052925,
year = {2023},
author = {Li, J and Liu, Z and Lu, J and Shen, M and Cheng, Y and Siddiqui, N and Zhou, H and Zhang, Q and Liu, J and Herrera, G and Hiya, FE and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Decreased Macular Choriocapillaris Perfusion in Eyes With Macular Reticular Pseudodrusen Imaged With Swept-Source OCT Angiography.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {4},
pages = {15},
pmid = {37052925},
issn = {1552-5783},
support = {R01 EY028753/EY/NEI NIH HHS/United States ; P30 EY014801/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; *Retinal Drusen/diagnosis ; Choroid ; Perfusion ; },
abstract = {PURPOSE: To determine if macular reticular pseudodrusen (RPD) were associated with markers of impaired macular choroidal perfusion, we investigated measurements of macular choriocapillaris (CC) flow deficits (FDs), CC thickness, and mean choroidal thickness (MCT) in eyes with macular RPD compared with normal eyes and eyes with soft drusen.<br><br>METHODS: Eyes with intermediate age-related macular degeneration (iAMD) and normal eyes underwent 6 &#xd7; 6 mm swept-source optical coherence tomography angiography (SS-OCTA) imaging to diagnose macular RPD, occupying over 25% of the fovea-centered 5 mm diameter circle, and measure outer retinal layer (ORL) thickness, CC FDs, CC thickness, MCT, and choroidal vascularity index (CVI) using previously published strategies within the same fovea-centered 5 mm circle.<br><br>RESULTS: Ninety eyes were included; 30 normal eyes, 30 eyes with soft drusen, and 30 eyes with macular RPD. The RPD eyes showed higher macular CC FDs than normal eyes (P < 0.001) and soft drusen eyes (P = 0.019). Macular CC thickness was decreased in RPD eyes compared with normal eyes (P < 0.001) and soft drusen eyes (P = 0.016). Macular MCT in RPD eyes was thinner than normal eyes (P = 0.005) and soft drusen eyes (P < 0.001). No statistically and clinically significant differences were found in the ORL thickness and CVI measurements between RPD eyes and the other two groups (all P > 0.05).<br><br>CONCLUSIONS: Eyes with macular RPD had decreased macular CC perfusion, decreased CC thickness, and decreased MCT measurements compared with normal and soft drusen eyes, suggesting that RPD may result from impaired choroidal perfusion.},
}
@article {pmid37052912,
year = {2023},
author = {Ayhan, MS and Faber, H and Kühlewein, L and Inhoffen, W and Aliyeva, G and Ziemssen, F and Berens, P},
title = {Multitask Learning for Activity Detection in Neovascular Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {4},
pages = {12},
pmid = {37052912},
issn = {2164-2591},
mesh = {Male ; Humans ; Female ; *Retina ; Neural Networks, Computer ; Machine Learning ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging ; },
abstract = {PURPOSE: The purpose of this study was to provide a comparison of performance and explainability of a multitask convolutional deep neuronal network to single-task networks for activity detection in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: From 70 patients (46 women and 24 men) who attended the University Eye Hospital T&#xfc;bingen, 3762 optical coherence tomography B-scans (right eye = 2011 and left eye = 1751) were acquired with Heidelberg Spectralis, Heidelberg, Germany. B-scans were graded by a retina specialist and an ophthalmology resident, and then used to develop a multitask deep learning model to predict disease activity in neovascular age-related macular degeneration along with the presence of sub- and intraretinal fluid. We used performance metrics for comparison to single-task networks and visualized the deep neural network (DNN)-based decision with t-distributed stochastic neighbor embedding and clinically validated saliency mapping techniques.<br><br>RESULTS: The multitask model surpassed single-task networks in accuracy for activity detection (94.2% vs. 91.2%). The area under the curve of the receiver operating curve was 0.984 for the multitask model versus 0.974 for the single-task model. Furthermore, compared to single-task networks, visualizations via t-distributed stochastic neighbor embedding and saliency maps highlighted that multitask networks' decisions for activity detection in neovascular age-related macular degeneration were highly consistent with the presence of both sub- and intraretinal fluid.<br><br>CONCLUSIONS: Multitask learning increases the performance of neuronal networks for predicting disease activity, while providing clinicians with an easily accessible decision control, which resembles human reasoning.<br><br>TRANSLATIONAL RELEVANCE: By improving nAMD activity detection performance and transparency of automated decisions, multitask DNNs can support the translation of machine learning research into clinical decision support systems for nAMD activity detection.},
}
@article {pmid37048613,
year = {2023},
author = {Prea, S and Guymer, R and Kong, G and Vingrys, A},
title = {Performance of a Smart Device over 12-Months for Home Monitoring of Patients with Intermediate Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {7},
pages = {},
pmid = {37048613},
issn = {2077-0383},
support = {1103013//National Health and Medical Research Council/ ; AJV and GK 2017//HealthTech Innovation Challenge/ ; },
abstract = {BACKGROUND: To determine the 12-month compliance with and retention of home monitoring (HM) with Melbourne Rapid Fields (MRFh) for patients with intermediate age-related macular degeneration (iAMD) and compare visual acuity (VA) and retinal sensitivity (RS) results to clinical measures.<br><br>METHODS: Participants were recruited to a 12-month HM study with weekly testing of vision with MRFh. Inclusion criteria were a diagnosis of iAMD, understand English instructions, VA &#x2265; 20/40, and access to an iPad. Supervised in-clinic testing of high contrast VA (HVA, ETDRS), low-luminance VA (LLVA, ETDRS with ND2 filter), and RS (Macular Integrity Assessment, MAIA, and MRF in-clinic, MRFc) was conducted every 6-months.<br><br>RESULTS: A total of 54 participants (67 &#xb1; 6.8 years) were enrolled. Compliance to weekly HM was 61% and study retention at 12-months was 50% of those with uptake (n = 46). No difference was observed between MRFc and MRFh across all RS and VA outcomes (p > 0.05). MRFh RS was higher than MAIA (29.1 vs. 27.1 dB, p < 0.001). MRFh HVA was not different from ETDRS (p = 0.08), but LLVA was 9 letters better (81.5 vs. 72.4 letters, p < 0.001).<br><br>CONCLUSIONS: Over 12-months, MRFh yields a moderate level of compliance with (61%) and retention (50%) of weekly testing. Further studies are required to assess the ability of MRFh to detect early progression to nAMD.},
}
@article {pmid37047721,
year = {2023},
author = {Tisi, A and Carozza, G and Leuti, A and Maccarone, R and Maccarrone, M},
title = {Dysregulation of Resolvin E1 Metabolism and Signaling in a Light-Damage Model of Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {24},
number = {7},
pages = {},
pmid = {37047721},
issn = {1422-0067},
support = {PRIN 2017-2017BTHJ4R//Italian Ministry od Health/ ; 07_DG_2022_12//University of L'Aquila/ ; },
mesh = {Animals ; Rats ; *Eicosapentaenoic Acid ; Cyclooxygenase 2 ; Rats, Sprague-Dawley ; *Macular Degeneration/etiology ; },
abstract = {Resolvin E1 (RvE1) is an eicosapentaenoic acid-derived lipid mediator involved in the resolution of inflammation. Here, we investigated whether RvE1 alterations may occur in an animal model of age-related macular degeneration (AMD). To this end, Sprague Dawley albino rats underwent light damage (LD), and retinas and serum were analyzed immediately or seven days after treatment. Western blot of retinas showed that the RvE1 receptor ChemR23 and the RvE1 metabolic enzymes 5-LOX and COX-2 were unchanged immediately after LD, but they were significantly up-regulated seven days later. Instead, the RvE1 receptor BLT1 was not modulated by LD, and neither was the RvE1 degradative enzyme 15-PGDH. Moreover, ChemR23, 5-LOX, COX-2 and BLT1 were found to be more expressed in the inner retina under all experimental conditions, as observed through ImageJ plot profile analysis. Of note, amacrine cells highly expressed BLT1, while ChemR23 was highly expressed in the activated microglia of the outer retina. ELISA assays also showed that LD rats displayed significantly higher circulating levels and reduced retinal levels of RvE1 compared to controls. Altogether, our data indicate that RvE1 metabolism and signaling are modulated in the LD model, suggesting a potentially relevant role of this pathway in AMD.},
}
@article {pmid37047703,
year = {2023},
author = {Wang, Y and Wang, J and Jiang, Y and Zhu, D and Ouyang, J and Yi, Z and Li, S and Jia, X and Xiao, X and Sun, W and Wang, P and Zhang, Q},
title = {New Insight into the Genotype-Phenotype Correlation of PRPH2-Related Diseases Based on a Large Chinese Cohort and Literature Review.},
journal = {International journal of molecular sciences},
volume = {24},
number = {7},
pages = {},
pmid = {37047703},
issn = {1422-0067},
support = {81970837//National Natural Science Foundation of China/ ; 202102010271//Science and Technology Planning Projects of Guangzhou/ ; },
mesh = {Humans ; Alleles ; Cohort Studies ; East Asian People/genetics ; Exome ; Genetic Association Studies ; Genotype ; *Macular Degeneration/genetics ; Mutation ; Pedigree ; Phenotype ; Retinal Dystrophies/genetics ; *Retinitis Pigmentosa/pathology ; },
abstract = {Variants in PRPH2 are a common cause of inherited retinal dystrophies with high genetic and phenotypic heterogeneity. In this study, variants in PRPH2 were selected from in-house exome sequencing data, and all reported PRPH2 variants were evaluated with the assistance of online prediction tools and the comparative validation of large datasets. All variants were classified based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Individuals with pathogenic or likely pathogenic variants of PRPH2 were confirmed by Sanger sequencing. Clinical characteristics were summarized. Ten pathogenic or likely pathogenic variants of PRPH2 were identified in 14 families. In our cohort, the most frequent variant was p.G305Afs*19, accounting for 33.3% (5/15) of alleles, in contrast to the literature, where p.R172G (11.6%, 119/1028) was the most common variant. Nine in-house families (63.8%) were diagnosed with retinitis pigmentosa (RP), distinct from the phenotypic spectrum in the literature, which shows that RP accounts for 27.9% (283/1013) and macular degeneration is more common (45.2%, 458/1013). Patients carrying missense variants predicted as damaging by all seven prediction tools and absent in the gnomAD database were more likely to develop RP compared to those carrying missense variants predicted as damaging with fewer tools or with more than one allele number in the gnomAD database (p = 0.001). The population-specific genetic and phenotypic spectra of PRPH2 were explored, and novel insight into the genotype-phenotype correlation of PRPH2 was proposed. These findings demonstrated the importance of assessing PRPH2 variants in distinct populations and the value of providing practical suggestions for the genetic interpretation of PRPH2 variants.},
}
@article {pmid37047689,
year = {2023},
author = {Dhingra, A and Tobias, JW and Philp, NJ and Boesze-Battaglia, K},
title = {Transcriptomic Changes Predict Metabolic Alterations in LC3 Associated Phagocytosis in Aged Mice.},
journal = {International journal of molecular sciences},
volume = {24},
number = {7},
pages = {},
pmid = {37047689},
issn = {1422-0067},
support = {P30 EY001583/EY/NEI NIH HHS/United States ; R01 EY026525/EY/NEI NIH HHS/United States ; R21 EY032743/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Male ; Mice ; Autophagy/genetics ; Inflammation/genetics/metabolism ; Lipids ; *Microtubule-Associated Proteins/metabolism ; Phagocytosis/genetics ; Retinal Pigment Epithelium/metabolism ; *Transcriptome ; },
abstract = {LC3b (Map1lc3b) plays an essential role in canonical autophagy and is one of several components of the autophagy machinery that mediates non-canonical autophagic functions. Phagosomes are often associated with lipidated LC3b to promote phagosome maturation in a process called LC3-associated phagocytosis (LAP). Specialized phagocytes, such as mammary epithelial cells, retinal pigment epithelial (RPE) cells, and sertoli cells, utilize LAP for optimal degradation of phagocytosed material, including debris. In the visual system, LAP is critical to maintain retinal function, lipid homeostasis, and neuroprotection. In a mouse model of retinal lipid steatosis-mice lacking LC3b (LC3b[-/-]), we observed increased lipid deposition, metabolic dysregulation, and enhanced inflammation. Herein, we present a non-biased approach to determine if loss of LAP mediated processes modulate the expression of various genes related to metabolic homeostasis, lipid handling, and inflammation. A comparison of the RPE transcriptome of WT and LC3b[-/-] mice revealed 1533 DEGs, with ~73% upregulated and 27% downregulated. Enriched gene ontology (GO) terms included inflammatory response (upregulated DEGs), fatty acid metabolism, and vascular transport (downregulated DEGs). Gene set enrichment analysis (GSEA) identified 34 pathways; 28 were upregulated (dominated by inflammation/related pathways) and 6 were downregulated (dominated by metabolic pathways). Analysis of additional gene families identified significant differences for genes in the solute carrier family, RPE signature genes, and genes with a potential role in age-related macular degeneration. These data indicate that loss of LC3b induces robust changes in the RPE transcriptome contributing to lipid dysregulation and metabolic imbalance, RPE atrophy, inflammation, and disease pathophysiology.},
}
@article {pmid37047648,
year = {2023},
author = {Kim, SK and Ban, JY and Kang, H and Park, SI},
title = {Anti-Apoptotic Effect of Chrysophanol Isolated from Cassia tora Seed Extract on Blue-Light-Induced A2E-Loaded Human Retinal Pigment Epithelial Cells.},
journal = {International journal of molecular sciences},
volume = {24},
number = {7},
pages = {},
pmid = {37047648},
issn = {1422-0067},
support = {(2022RIS-005)//National Research Foundation of Korea (NRF)/ ; },
mesh = {Humans ; *Cassia/genetics ; Anthraquinones/pharmacology/metabolism ; Light ; Plant Extracts/chemistry ; Retinal Pigments/metabolism ; RNA, Messenger/genetics/metabolism ; Epithelial Cells/metabolism ; Seeds/metabolism ; Retinal Pigment Epithelium/metabolism ; Retinoids/pharmacology ; },
abstract = {The seeds of Cassia tora (C. tora) species mainly contain anthraquinone, anthraquinone glycoside, and naphthalene derivatives. We investigated the anti-apoptotic effects of C. tora seed extract and its isolated compounds on blue-light-induced lipofuscin (A2E)-loaded human retinal pigment epithelial (RPE) cells. For analysis of the C. tora extract, high-performance liquid chromatography method was used. A2E-loaded human retinal pigment epithelial cells and blue light were used to create excessive photo-oxidation to induce cell death. Lactate dehydrogenase (LDH) assay was used to measure cell cytotoxicity, and the mRNA expression of genes involved in apoptosis was examined to evaluate the mechanism of cell death. C. tora extract, n-hexane fraction, and chrysophanol were found to inhibit apoptotic cell death. Additionally, C. tora extract, n-hexane fraction, and chrysophanol reduced the mRNA expression of genes involved in the apoptosis pathway. C. tora and chrysophanol were considered to inhibit apoptosis and oxidative stress response. The major component of C. tora has a protective effect against apoptosis. The ingredients of C. tora can be used as therapeutic substances or to prevent diseases caused by the excessive oxidation of A2E substances in the retina, such as in age-related macular degeneration.},
}
@article {pmid37047392,
year = {2023},
author = {Hegde, KR and Puche, AC and Szmacinski, H and Fuller, K and Ray, K and Patel, N and Lengyel, I and Thompson, RB},
title = {Fluorescence Lifetime Imaging of Human Sub-RPE Calcification In Vitro Following Chlortetracycline Infusion.},
journal = {International journal of molecular sciences},
volume = {24},
number = {7},
pages = {},
pmid = {37047392},
issn = {1422-0067},
support = {R01 AI172487/AI/NIAID NIH HHS/United States ; R01 EY030443/EY/NEI NIH HHS/United States ; NIA 030443-03S1/AG/NIA NIH HHS/United States ; NIH RO1 EY 030443/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Chlortetracycline ; Pilot Projects ; *Macular Degeneration ; Retina ; *Calcinosis ; Retinal Pigment Epithelium ; },
abstract = {We have shown that all sub-retinal pigment epithelial (sub-RPE) deposits examined contain calcium phosphate minerals: hydroxyapatite (HAP), whitlockite (Wht), or both. These typically take the form of ca. 1 μm diameter spherules or >10 μm nodules and appear to be involved in the development and progression of age-related macular degeneration (AMD). Thus, these minerals may serve as useful biomarkers the for early detection and monitoring of sub-RPE changes in AMD. We demonstrated that HAP deposits could be imaged in vitro by fluorescence lifetime imaging microscopy (FLIM) in flat-mounted retinas using legacy tetracycline antibiotics as selective sensors for HAP. As the contrast on a FLIM image is based on the difference in fluorescence lifetime and not intensity of the tetracycline-stained HAP, distinguishing tissue autofluorescence from the background is significantly improved. The focus of the present pilot study was to assess whether vascular perfusion of the well tolerated and characterized chlortetracycline (widely used as an orally bioavailable antibiotic) can fluorescently label retinal HAP using human cadavers. We found that the tetracycline delivered through the peripheral circulation can indeed selectively label sub-RPE deposits opening the possibility for its use for ophthalmic monitoring of a range of diseases in which deposit formation is reported, such as AMD and Alzheimer disease (AD).},
}
@article {pmid37047224,
year = {2023},
author = {Lizama, BN and Kahle, J and Catalano, SM and Caggiano, AO and Grundman, M and Hamby, ME},
title = {Sigma-2 Receptors-From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases.},
journal = {International journal of molecular sciences},
volume = {24},
number = {7},
pages = {},
pmid = {37047224},
issn = {1422-0067},
mesh = {Animals ; *Alzheimer Disease/drug therapy ; *Receptors, sigma/metabolism ; alpha-Synuclein/metabolism ; Amyloid beta-Peptides ; Biology ; *Lewy Body Disease ; },
abstract = {There is a large unmet medical need to develop disease-modifying treatment options for individuals with age-related degenerative diseases of the central nervous system. The sigma-2 receptor (S2R), encoded by TMEM97, is expressed in brain and retinal cells, and regulates cell functions via its co-receptor progesterone receptor membrane component 1 (PGRMC1), and through other protein-protein interactions. Studies describing functions of S2R involve the manipulation of expression or pharmacological modulation using exogenous small-molecule ligands. These studies demonstrate that S2R modulates key pathways involved in age-related diseases including autophagy, trafficking, oxidative stress, and amyloid-β and α-synuclein toxicity. Furthermore, S2R modulation can ameliorate functional deficits in cell-based and animal models of disease. This review summarizes the current evidence-based understanding of S2R biology and function, and its potential as a therapeutic target for age-related degenerative diseases of the central nervous system, including Alzheimer's disease, α-synucleinopathies, and dry age-related macular degeneration.},
}
@article {pmid37043599,
year = {2024},
author = {Ambati, J and Gelfand, BD},
title = {Response to 'Early Onset Drusen and RPE Dysfunction in a Patient with NLRP3-AID'.},
journal = {Ocular immunology and inflammation},
volume = {32},
number = {5},
pages = {778},
pmid = {37043599},
issn = {1744-5078},
support = {R01 EY029799/EY/NEI NIH HHS/United States ; R01 EY031039/EY/NEI NIH HHS/United States ; R01 EY032512/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; *Retinal Pigment Epithelium/pathology ; *Retinal Drusen/diagnosis ; Tomography, Optical Coherence ; Mutation ; },
}
@article {pmid37043090,
year = {2023},
author = {Prince, J and Kumar, D and Ghosh, A and Arevalo, JF and Zhang, AY},
title = {Surgical Management of Diabetic Macular Edema.},
journal = {Current diabetes reports},
volume = {23},
number = {6},
pages = {119-125},
pmid = {37043090},
issn = {1539-0829},
mesh = {Humans ; *Macular Edema/surgery/etiology ; *Diabetic Retinopathy/surgery/complications ; Endothelial Growth Factors ; Vitrectomy/adverse effects/methods ; Tomography, Optical Coherence/adverse effects ; Laser Coagulation/adverse effects/methods ; Retrospective Studies ; *Diabetes Mellitus/etiology ; },
abstract = {PURPOSE OF REVIEW: Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention.<br><br>RECENT FINDINGS: Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement. Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.},
}
@article {pmid37043002,
year = {2023},
author = {Lando, L and Nguyen, AX and Li, RTH and Megaw, R and Dhillon, B and Borooah, S},
title = {Anterior segment phenotypic changes in late-onset retinal degeneration with Ser163Arg mutation in CTRP5/C1QTNF5.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {9},
pages = {2507-2516},
pmid = {37043002},
issn = {1435-702X},
support = {219607/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Male ; Humans ; Middle Aged ; Longitudinal Studies ; Prospective Studies ; *Retinal Degeneration/diagnosis/genetics ; Mutation ; *Iris Diseases ; Atrophy ; Collagen ; },
abstract = {PURPOSE: Late-onset retinal degeneration (L-ORD) is a rare retinal dystrophy with anterior segment (AS) abnormalities, including long anterior zonules (LAZ) and iris atrophy. This investigation evaluates AS changes in a L-ORD cohort.<br><br>METHODS: Prospective, longitudinal study including L-ORD individuals (Ser163Arg) with ocular exam and standard slit-lamp photographs between 2011 and 2022. AS images were merged and assessed for LAZ number and zonule-free zone (ZFZ) radius. Further clinical findings such as iris atrophy patterns were reported descriptively.<br><br>RESULTS: Twelve eyes of 6 patients (4 males, median age&#x2009;=&#x2009;60.5&#xa0;years) were included, showing a median of 160 (11-372) LAZs, mainly localized superiorly (39%) and inferiorly (24%). There was a high inter-ocular correlation (rs&#x2009;=&#x2009;0.94, p&#x2009;<&#x2009;0.01), no difference in LAZ count between eyes (p&#x2009;=&#x2009;0.82), and an inverse relationship between LAZ and age (r&#x2009;=&#x2009;&#x2009;-&#x2009;0.82; p&#x2009;<&#x2009;0.05). The ZFZ had median 2.1&#xa0;mm (1.3-5.4), with no inter-ocular difference (p&#x2009;=&#x2009;0.31). Iris transillumination defects occurred in 11/12 eyes, with 4 major patterns identified: pupillary ruff rarefaction (10/12), patchy atrophy (6/12), notched defects (6/12), and radial streaks (2/12). In a short-term follow-up of 5.9&#xa0;years, 4 eyes showed a reduction in LAZ count to median 139.5 (67-169) (p&#x2009;=&#x2009;0.50) and a concomitant increase in ZFZ measurement to median 2.2 (1.7-2.6) (p&#x2009;=&#x2009;0.17).<br><br>CONCLUSION: This study confirms symmetric LAZs count and ZFZ in L-ORD, with ZFZ measurements smaller than in previous cohorts. A reduction in LAZs count and an increase in ZFZ with age were suggested longitudinally, yet findings need further evaluation as follow-up was limited to two cases.},
}
@article {pmid37041490,
year = {2023},
author = {Holm, DL and Nielsen, MK and Højsted, BB and Sørensen, TL},
title = {Vision-related quality of life is selectively affected by comorbidities in patients with geographic atrophy.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {153},
pmid = {37041490},
issn = {1471-2415},
mesh = {Humans ; Quality of Life ; *Geographic Atrophy ; Prospective Studies ; *Vision, Low ; Fundus Oculi ; *Pulmonary Disease, Chronic Obstructive ; },
abstract = {BACKGROUND: The atrophic late stage of age-related macular degeneration (AMD) is termed geographic atrophy (GA), and affects visual acuity (VA) as well as quality of life (QoL). Previous studies have found that best-corrected VA (BCVA), the standard vision assessment often underrepresents functional deficits. Therefore, the purpose of this study was to evaluate the correlation between atrophic lesion size, VA and QoL measured with the National Eye Institute Visual Function Questionnaire (VFQ-39) in a Danish population. Moreover, we wanted to evaluate the correlation between comorbidities, behavioural factors, and QoL.<br><br>METHODS: This was prospective clinical study of 51 patients with GA in one or both eyes, of these 45 patients had bilateral GA. Patients were consecutively included between April 2021 and February 2022. All patients filled in the VFQ-39 questionnaire except the subscales "ocular pain" and "peripheral vision." Lesion size was measured from fundus autoflourescense images, and BCVA was assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol.<br><br>RESULTS: We found an overall low score in each VFQ-39 subscale scores reflected by GA. Lesion size and VA were both significantly associated with all VFQ-39 subscale scores except for "general health." VA showed a larger effect on QoL than lesion size. Chronic obstructive pulmonary disease (COPD) was associated with a lower score in the subscale score "general health" but none of the other subscale scores were affected. Cardiovascular disease (CVD) was associated with a lower BCVA as well as in QoL reflected in the subscale scores "poor general vision," "near activities," and "dependency" of VFQ-39.<br><br>CONCLUSION: Both atrophic lesion size and visual acuity affects QoL in Danish patients with GA, who reports an overall poor QoL. CVD seems to have a negative effect on disease, as well as in VFQ-39 in several subscales, whereas COPD did not affect disease severity or vision-related subscales in VFQ-39.},
}
@article {pmid37041349,
year = {2023},
author = {Gao, Y and Lu, F and Li, X and Dai, H and Liu, K and Liu, X and Sun, Z and Xiang, J and Ding, L and Liang, C and Wang, Y and Shen, Z and Zhang, M},
title = {Safety and tolerability of oral vorolanib for neovascular (wet) age-related macular degeneration: a phase I, open-label study.},
journal = {Eye (London, England)},
volume = {37},
number = {15},
pages = {3228-3233},
pmid = {37041349},
issn = {1476-5454},
abstract = {OBJECTIVE: To evaluate the efficacy and safety of oral vorolanib for the treatment of neovascular (wet) age-related macular degeneration (nAMD).<br><br>METHODS: In the dose escalation, participants received ascending doses of oral vorolanib (25-100&#x2009;mg daily). In the dose expansion, participants received recommended doses (25 and 50&#x2009;mg daily).<br><br>RESULTS: Between March 15, 2015, and January 23, 2019, 41 participants were enrolled in 6 centres in China. At the data cut-off (November 14, 2019), two dose-limiting toxicities (DLTs) were observed during dose escalation (one in the 75&#x2009;mg cohort and one in the 100&#x2009;mg cohort). The maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 33 (80.5%) participants, and grade 3 or higher TRAEs occurred in 12 (29.3%) participants. No fatal TRAEs were observed. Increases in the mean best-corrected visual acuity (BCVA) from baseline to Day 360 of +7.7 letters (range, -5-29; n&#x2009;=&#x2009;41) were observed in participants who were administered vorolanib. Corresponding reductions in mean central subfield thickness (CST) and choroidal neovascularization (CNV) area at Day 360 were observed in these three groups.<br><br>CONCLUSIONS: Oral administration of vorolanib improved visual outcomes in participants with nAMD with manageable systemic safety profiles.},
}
@article {pmid37040734,
year = {2023},
author = {Cavalleri, M and Tombolini, B and Sacconi, R and Gatta, G and Valeri, R and Bandello, F and Querques, G},
title = {Real-Life Experience and Predictors of Visual Outcomes with Intravitreal Brolucizumab Switch for Treatment of Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {2},
pages = {158-168},
doi = {10.1159/000530544},
pmid = {37040734},
issn = {1423-0267},
mesh = {Aged ; Aged, 80 and over ; Humans ; Male ; Angiogenesis Inhibitors ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/diagnosis/drug therapy ; *Antibodies, Monoclonal, Humanized/therapeutic use ; },
abstract = {INTRODUCTION: To analyze visual and anatomical outcomes after switch to intravitreal brolucizumab therapy in eyes affected by neovascular age-related macular degeneration (nAMD) previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.<br><br>METHODS: Retrospective study of eyes with nAMD that underwent intravitreal brolucizumab at San Raffaele Hospital (Milan, Italy) or San Rocco Clinical Institute (Ome, Italy) between January 2021 and July 2022. All study eyes had persistent residual retinal fluid after receiving at least 3 intravitreal injections of other anti-VEGF agents prior to switch to brolucizumab.<br><br>RESULTS: Among 66 eyes from 60 patients (35 males; mean age 76.5 &#xb1; 7.4 years) with nAMD, 43 (65.2%) eyes received a complete loading dose of 3 brolucizumab injections, while 15 (22.7%) and 8 (12.1%) eyes were treated with 2 or 1 brolucizumab injections, respectively. The average number of brolucizumab injections was 2.5 during 4.0 &#xb1; 2.0 months (mean interval between two injections of 51.2 days). Lower letter gains (<5 letter improvement from baseline) were found in eyes that did not complete a loading dose, after a greater number of previous anti-VEGF injections, after a longer duration of disease, and in eyes with a greater rate of macular atrophy at baseline. No serious ocular or systemic adverse events were found after switch to brolucizumab.<br><br>CONCLUSION: nAMD eyes with persistent residual retinal fluid despite frequent anti-VEGF treatment can still gain functional and anatomical improvements after switch to brolucizumab therapy. Despite a relevant heterogeneity in patients' response to brolucizumab, we identified potential biomarkers for functional and anatomical improvement.},
}
@article {pmid37039948,
year = {2023},
author = {Mori, R and Honda, S and Gomi, F and Tsujikawa, A and Koizumi, H and Ochi, H and Ohsawa, S and Okada, AA and , },
title = {Efficacy, durability, and safety of faricimab up to every 16 weeks in patients with neovascular age-related macular degeneration: 1-year results from the Japan subgroup of the phase 3 TENAYA trial.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {3},
pages = {301-310},
pmid = {37039948},
issn = {1613-2246},
support = {F. Hoffmann-La Roche Ltd.//F. Hoffmann-La Roche Ltd./ ; Genentech, Inc//Genentech, Inc/ ; Chugai Pharmaceutical Co.//Chugai Pharmaceutical Co./ ; },
mesh = {Humans ; Angiogenesis Inhibitors ; Japan/epidemiology ; Visual Acuity ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor ; *Macular Degeneration/drug therapy ; Recombinant Fusion Proteins ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To evaluate the 1-year efficacy, durability, and safety of faricimab versus aflibercept in patients with neovascular age-related macular degeneration (nAMD) enrolled in the Japan subgroup of the TENAYA trial.<br><br>STUDY DESIGN: TENAYA (NCT03823287) was a global, phase 3, multicenter, randomized, active comparator-controlled, double-masked, noninferiority, parallel-group, 112-week trial. After completion of global enrollment, additional patients were enrolled in the Japan extension of TENAYA.<br><br>METHODS: Treatment-na&#xef;ve patients aged&#x2009;&#x2265;&#x2009;50 years with nAMD were randomized (1:1) to intravitreal faricimab 6&#xa0;mg up to every 16 weeks (Q16W) after 4 initial Q4W doses based on disease activity at weeks 20 and 24 or aflibercept 2&#xa0;mg Q8W after 3 initial Q4W doses. Primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48. Anatomical/durability outcomes were assessed.<br><br>RESULTS: Overall, 133 patients were included in the TENAYA Japan subgroup analysis (faricimab, n&#x2009;=&#x2009;66; aflibercept, n&#x2009;=&#x2009;67). The adjusted mean (95% confidence interval) BCVA changes were +&#x2009;7.1 (4.6&#x2012;9.7) and +&#x2009;7.7 (5.2&#x2012;10.1) letters in the faricimab and aflibercept treatment groups, respectively. At week 48, 66.1%, 22.6%, and 11.3% of patients in the faricimab group were on Q16W, Q12W, Q8W and dosing intervals, respectively. Ocular adverse event rates were similar between treatment groups (faricimab, n&#x2009;=&#x2009;14 [21.2%] versus aflibercept, n&#x2009;=&#x2009;17 [25.4%]).<br><br>CONCLUSION: The TENAYA Japan subgroup analysis showed that faricimab up to Q16W had sustained efficacy with an acceptable safety profile. These findings are consistent with the global TENAYA and LUCERNE findings.},
}
@article {pmid37039377,
year = {2023},
author = {Yamashita, K and Ostrovidov, S and Raut, B and Hori, T and Nashimoto, Y and Nagai, N and Abe, T and Kaji, H},
title = {Minimally Invasive Sub-Retinal Transplantation of RPE-J Cells on a Biodegradable Composite PCL/Collagen Nanosheet.},
journal = {Cell transplantation},
volume = {32},
number = {},
pages = {9636897231165117},
pmid = {37039377},
issn = {1555-3892},
mesh = {Rats ; Animals ; *Retinal Pigment Epithelium ; Retina ; Collagen ; *Macular Degeneration/surgery ; Cell Transplantation ; },
abstract = {Retinal cells are irreparably damaged by diseases such as age-related macular degeneration (AMD). A promising method to restore partial or whole vision is through cell-based transplantation to the damaged location. However, cell transplantation using conventional vitreous surgery is an invasive procedure that may induce infections and has a high failure rate of cell engraftment. In this study, we describe the fabrication of a biodegradable composite nanosheet used as a substrate to support retinal pigment epithelial (RPE-J) cells, which can be grafted to the sub-retinal space using a minimally invasive approach. The nanosheet was fabricated using polycaprolactone (PCL) and collagen in 80:20 weight ratio, and had size of 200 µm in diameter and 300 nm in thickness. These PCL/collagen nanosheets showed excellent biocompatibility and mechanical strength in vitro. Using a custom designed 27-gauge glass needle, we successfully transplanted an RPE-J cell loaded nanosheet into the sub-retinal space of a rat model with damaged photoreceptors. The cell loaded nanosheet did not trigger immunological reaction within 2 weeks of implantation and restored the retinal environment. Thus, this composite PCL/collagen nanosheet holds great promise for organized cell transplantation, and the treatment of retinal diseases.},
}
@article {pmid37038336,
year = {2024},
author = {Oribio-Quinto, C and Herranz-Heras, JC and Burgos-Blasco, B and Alarcon-Garcia, AD and Fernández-Vigo, JI},
title = {Clinical and multimodal imaging findings in a case of serous maculopathy with absence of retinal pigment epithelium (SMARPE).},
journal = {European journal of ophthalmology},
volume = {34},
number = {1},
pages = {NP66-NP69},
doi = {10.1177/11206721231169310},
pmid = {37038336},
issn = {1724-6016},
mesh = {Humans ; Female ; Aged ; Retinal Pigment Epithelium/pathology ; Indocyanine Green ; *Macular Degeneration/pathology ; *Retinal Degeneration ; Tomography, Optical Coherence/methods ; *Choroidal Neovascularization/diagnosis ; Multimodal Imaging ; Fluorescein Angiography/methods ; *Central Serous Chorioretinopathy/diagnosis ; },
abstract = {INTRODUCTION: The differential diagnosis for serous SRF can involve diseases with widely different pathogenic mechanisms that can range from vascular ocular diseases to ocular tumours and paraneoplastic syndromes. Recently, van Dijk et al. have described in three patients a new entity which they have called serous maculopathy with an absence of retinal pigment epithelium (SMARPE). We hereby describe a case of this infrequent macular disease and report its characteristic findings on multimodal imaging.<br><br>CASE DESCRIPTION: We present the case of a 65-year-old hyperopic woman with a three-year history of visual acuity (VA) loss in her left eye. Prior optical coherence tomography (OCT) had revealed the presence of serous subretinal fluid that had shown no response to treatment with intravitreal injections. On swept source OCT angiography scan, no macular alterations in the retinal vascular plexus structure were noted and there was no evidence of choroidal neovascularization. Ultra-widefield fluorescence angiography of the left eye revealed an early hyperfluorescent macular spot corresponding to the area of absent RPE and late fluorescein pooling. On ultra-widefield indocyanine green angiography there were no central or peripheral abnormalities of choroidal vascularization.<br><br>CONCLUSION: This recently described entity should be considered as a differential diagnosis in persistent serous subretinal fluid. Multimodal imaging helps differentiate SMARPE from its main differential diagnoses, and care should be taken to identify and differentiate it from similar conditions to avoid unnecessary treatment with its possible side effects and complications.},
}
@article {pmid37037364,
year = {2023},
author = {Dörschmann, P and Akkurt, H and Kopplin, G and Mikkelsen, MD and Meyer, AS and Roider, J and Klettner, A},
title = {Establishment of specific age-related macular degeneration relevant gene expression panels using porcine retinal pigment epithelium for assessing fucoidan bioactivity.},
journal = {Experimental eye research},
volume = {231},
number = {},
pages = {109469},
doi = {10.1016/j.exer.2023.109469},
pmid = {37037364},
issn = {1096-0007},
mesh = {Animals ; Swine ; *Retinal Pigment Epithelium/metabolism ; Lipopolysaccharides/pharmacology ; Vascular Endothelial Growth Factor A/metabolism ; Hydrogen Peroxide/metabolism ; *Macular Degeneration/metabolism ; Polysaccharides/pharmacology/metabolism/therapeutic use ; Oxidative Stress ; Inflammation/metabolism ; Gene Expression ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe vision loss in industrialized nations. Important factors in pathogenesis are oxidative stress, inflammation, and, in the wet form of AMD, angiogenesis. Fucoidans, sulfated polysaccharides from brown algae, may have antioxidant, anti-inflammatory, and antiangiogenic effects. In this study, we established specific gene expression panels for inflammation, oxidative stress and angiogenesis in porcine retinal pigment epithelium (RPE), and investigated the effect of fucoidans on gene expression under different noxious agents.<br><br>METHODS: Primary porcine RPE cells cultured for at least 14 days were used. Using viability assays with tetrazolium bromide and real-time polymerase chain reaction of marker genes, positive controls were established for appropriate concentrations and exposure times of selected noxious agents (lipopolysaccharide (LPS), H2O2, CoCl2). Three different AMD relevant gene panels specific for porcine RPE for inflammation, oxidative stress, and angiogenesis were established, and the influence of fucoidans (mainly Fucus vesiculosus; FV) on gene expression was investigated.<br><br>RESULTS: The following was shown by gene expression analyses: (1) Inflammation panel: Expression of 18 genes was affected under LPS (three days). Among them, LPS increased genes for interleukin 1 receptor 2, interleukin 8, cyclooxygenase-2 and vascular cell adhesion protein 1 expression which were diminished when FV was present. (2) Oxidative stress panel: Under stimulation of H2O2 (one day) and LPS (one day), expression of a total of 15 genes was affected. LPS induced increase in genes for superoxide dismutase-1, C-X-C motif chemokine 10, and CC chemokine ligand-5 expression was not detected when FV was present. (3) Angiogenesis panel: Under stimulation with CoCl2 (three days) expression of six genes was affected, with the increase of genes for angiopoietin 2, vascular endothelial growth factor receptor-1, and follistatin being diminished when FV was present.<br><br>CONCLUSION: Three specific gene expression panels for porcine RPE that map genes for three of the major pathological factors of AMD, inflammation, oxidative stress, and angiogenesis, were established. Further, we demonstrated that fucoidans can reduce stress related gene activation in all of these three major pathogenic pathways. This study is another indication that fucoidans can act on different pathomechanisms of AMD simultaneously, which provides further evidence for fucoidans as a possible drug for treatment and prevention of AMD.},
}
@article {pmid37037324,
year = {2023},
author = {Monje-Fernández, L and Gallego-Pinazo, R and Cordero-Coma, M and Donate-López, J and Coco-Martín, RM and Dolz-Marco, R},
title = {Evaluation of non-exudative tomographic signs in cases of exudative age-related macular degeneration.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {98},
number = {5},
pages = {276-280},
doi = {10.1016/j.oftale.2023.03.008},
pmid = {37037324},
issn = {2173-5794},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Fluorescein Angiography ; Retina/pathology ; *Macular Degeneration/diagnostic imaging/pathology ; Atrophy/pathology ; },
abstract = {OBJECTIVE: To analyse the prevalence of non-exudative tomographic signs (onion sign, pseudoswelling, external retinal tubulation, pseudocysts, subretinal clefts and macular atrophy) in patients with neovascular age-related macular degeneration.<br><br>MATERIAL AND METHODS: A total of 174 eyes of patients with neovascular age-related macular degeneration who had not received previous treatment were included in the study. Visual acuity, neovascularization activity, and the appearance or not of the different signs under study were assessed at times 0 (initial visit), 4 months, one year, year and a half, and at 2 and 3 years of follow-up. The following were also evaluated: age, sex, affected eye and type of neovascularization (1, 2, 3, polypoid or mixed). The analysis were performed using the statistical software R (version 3.3.2) and the glmmADMB package (version 0.8.3.3).<br><br>RESULTS: The presence of pseudocysts and external retinal tubulation increases throughout the follow-up. The onion sign begins with an ascending frequency up to 12 months, then decreases at 18 months and increases again at 24 months. Regarding pseudowelling, it maintains an increase until 18 months to finally decrease. Subretinal clefts is the rarest sign, presenting in 1.1% on the first visit. Finally, macular atrophy, present in 12.6% of the eyes initially, is found in 25% after 2 years.<br><br>CONCLUSION: Pseudocysts, external retinal tubulation and macular atrophy were the most prevalent signs, while subretinal clefts were the most infrequent.},
}
@article {pmid37034930,
year = {2023},
author = {Aubin, G and Phillips, N and Jaiswal, A and Johnson, AP and Joubert, S and Bachir, V and Kehayia, E and Wittich, W},
title = {Visual and cognitive functioning among older adults with low vision before vision rehabilitation: A pilot study.},
journal = {Frontiers in psychology},
volume = {14},
number = {},
pages = {1058951},
pmid = {37034930},
issn = {1664-1078},
abstract = {INTRODUCTION: The occurrence of age-related vision changes is inevitable. However, some of these changes can become pathological. Research indicates that vision and hearing loss is correlated with age-related cognitive decline, and with a higher risk of developing dementia due to Alzheimer's disease. Low vision rehabilitation could possibly be a protective factor against cognitive decline, as it provides the clients with compensatory strategies to overcome their visual deficits.<br><br>OBJECTIVES AND HYPOTHESIS: The aim of this pilot study was to assess correlations between visual and cognitive functions in older adults referred for low vision rehabilitation. We hypothesized that more severe impairment of visual acuity and contrast sensitivity would be correlated with more advanced levels of cognitive impairment. The second objective was to examine which of these correlations would remain significant once established variables that influence cognition are statistically removed (e.g., age, education).<br><br>METHODS: Thirty-eight older adults (age range: 66-97&#x2009;years old) with a visual impairment (acuity <20/70) were recruited before the onset of their low vision rehabilitation. They underwent vision (reading acuity, reading speed, contrast sensitivity), hearing (audiogram, speech-in-noise perception) and cognitive (global cognition, memory, executive functions) testing, and demographic information was obtained.<br><br>RESULTS AND DISCUSSION: Correlations among global cognition and visual aid use, memory and reading speed, memory and contrast sensitivity, memory, and visual aid use, and between executive functions and contrast sensitivity were significant. Correlations between contrast sensitivity and memory, as well as between global cognition and visual aid use remained significant after controlling for age and education. The present study is relevant to clinicians who are assessing the cognitive status of older adults, such as neuropsychologists, because it highlights the importance of considering low vision when administering neuropsychological tests, especially to persons who have not yet received rehabilitation for their visual impairment.},
}
@article {pmid37033028,
year = {2023},
author = {Ali, SG and Wang, X and Li, P and Jung, Y and Bi, L and Kim, J and Chen, Y and Feng, DD and Magnenat Thalmann, N and Wang, J and Sheng, B},
title = {A systematic review: Virtual-reality-based techniques for human exercises and health improvement.},
journal = {Frontiers in public health},
volume = {11},
number = {},
pages = {1143947},
pmid = {37033028},
issn = {2296-2565},
mesh = {Humans ; Child ; Artificial Intelligence ; *Autism Spectrum Disorder ; *Persons with Disabilities ; *Motor Disorders ; *Virtual Reality ; *Nervous System Diseases ; },
abstract = {Virtual Reality (VR) has emerged as a new safe and efficient tool for the rehabilitation of many childhood and adulthood illnesses. VR-based therapies have the potential to improve both motor and functional skills in a wide range of age groups through cortical reorganization and the activation of various neuronal connections. Recently, the potential for using serious VR-based games that combine perceptual learning and dichoptic stimulation has been explored for the rehabilitation of ophthalmological and neurological disorders. In ophthalmology, several clinical studies have demonstrated the ability to use VR training to enhance stereopsis, contrast sensitivity, and visual acuity. The use of VR technology provides a significant advantage in training each eye individually without requiring occlusion or penalty. In neurological disorders, the majority of patients undergo recurrent episodes (relapses) of neurological impairment, however, in a few cases (60-80%), the illness progresses over time and becomes chronic, consequential in cumulated motor disability and cognitive deficits. Current research on memory restoration has been spurred by theories about brain plasticity and findings concerning the nervous system's capacity to reconstruct cellular synapses as a result of interaction with enriched environments. Therefore, the use of VR training can play an important role in the improvement of cognitive function and motor disability. Although there are several reviews in the community employing relevant Artificial Intelligence in healthcare, VR has not yet been thoroughly examined in this regard. In this systematic review, we examine the key ideas of VR-based training for prevention and control measurements in ocular diseases such as Myopia, Amblyopia, Presbyopia, and Age-related Macular Degeneration (AMD), and neurological disorders such as Alzheimer, Multiple Sclerosis (MS) Epilepsy and Autism spectrum disorder. This review highlights the fundamentals of VR technologies regarding their clinical research in healthcare. Moreover, these findings will raise community awareness of using VR training and help researchers to learn new techniques to prevent and cure different diseases. We further discuss the current challenges of using VR devices, as well as the future prospects of human training.},
}
@article {pmid37032564,
year = {2023},
author = {, and , },
title = {[Evidence-based guidelines for diagnosis and treatment of age-related macular degeneration in China (2023)].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {59},
number = {5},
pages = {347-366},
doi = {10.3760/cma.j.cn112142-20221222-00649},
pmid = {37032564},
issn = {0412-4081},
mesh = {Humans ; Aged ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; *Ophthalmology ; },
abstract = {Age-related macular degeneration (AMD) is the main cause of low vision and even blindness in the elderly. With the aging of our population, the number of AMD patients will continue to rise. In the past decade, the rapid development of ocular fundus imaging technology has provided a new perspective and approach for the classification, diagnosis and follow-up of AMD. The advent of new drugs has provided more diverse intervention and treatment methods for AMD, especially for neovascular AMD, and the emphasis on accurate and individualized treatment has put forward higher requirements for retinal specialists. Therefore, based on the latest evidence-based medical information, combined with the international guidelines and the current situation of China's social and economic development, experts from the Chinese Vitreo-Retinal Society of Chinese Medical Association, the Fundus Disease Group of Chinese Ophthalmologist Association, and the National Clinical Research Center for Eye Diseases gave recommendations around eight clinical problems and formed China's guidelines for the clinical diagnosis and treatment of AMD. With the implementation of these guidelines, we can standardize the diagnosis, treatment, prevention and follow-up of AMD in China. (This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on April 6, 2023).},
}
@article {pmid37031905,
year = {2023},
author = {Wu, KY and Michael, R and Kalevar, A},
title = {Comment on: Intermittent Fasting Is Associated With a Decreased Risk of Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {252},
number = {},
pages = {332-333},
doi = {10.1016/j.ajo.2023.01.031},
pmid = {37031905},
issn = {1879-1891},
mesh = {Humans ; *Intermittent Fasting ; *Macular Degeneration/diagnosis/etiology/prevention &amp; control ; Risk Factors ; },
}
@article {pmid37031903,
year = {2023},
author = {Choi, EY and Lee, M},
title = {Reply to Comment on Intermittent Fasting is Associated with a Decreased Risk of Age-related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {252},
number = {},
pages = {334-335},
doi = {10.1016/j.ajo.2023.03.028},
pmid = {37031903},
issn = {1879-1891},
mesh = {Humans ; *Intermittent Fasting ; *Macular Degeneration/prevention &amp; control ; Risk Factors ; },
}
@article {pmid37031820,
year = {2023},
author = {He, D and Tao, L and Cai, B and Chen, X and Wang, Y and Li, S and Liao, C and Chen, Y and Chen, J and Liu, Z and Wu, Y},
title = {eIF2α incites photoreceptor cell and retina damage by all-trans-retinal.},
journal = {The Journal of biological chemistry},
volume = {299},
number = {5},
pages = {104686},
pmid = {37031820},
issn = {1083-351X},
mesh = {Animals ; Humans ; Mice ; Activating Transcription Factor 4/metabolism ; Apoptosis ; ATP-Binding Cassette Transporters/metabolism ; Photoreceptor Cells, Vertebrate/metabolism ; Retina/metabolism ; *Retinal Degeneration/genetics/metabolism ; Retinal Pigment Epithelium/metabolism ; *Retinaldehyde/metabolism ; *Stargardt Disease/metabolism ; *Eukaryotic Initiation Factor-2/genetics/metabolism ; },
abstract = {Dry age-related macular degeneration (AMD) and recessive Stargardt's disease (STGD1) lead to irreversible blindness in humans. The accumulation of all-trans-retinal (atRAL) induced by chaos in visual cycle is closely associated with retinal atrophy in dry AMD and STGD1 but its critical downstream signaling molecules remain ambiguous. Here, we reported that activation of eukaryotic translation initiation factor 2α (eIF2α) by atRAL promoted retinal degeneration and photoreceptor loss through activating c-Jun N-terminal kinase (JNK) signaling-dependent apoptosis and gasdermin E (GSDME)-mediated pyroptosis. We determined that eIF2α activation by atRAL in photoreceptor cells resulted from endoplasmic reticulum homeostasis disruption caused at least in part by reactive oxygen species production, and it activated JNK signaling independent of and dependent on activating transcription factor 4 and the activating transcription factor 4/transcription factor C/EBP homologous protein (CHOP) axis. CHOP overexpression induced apoptosis of atRAL-loaded photoreceptor cells through activating JNK signaling rather than inhibiting the expression of antiapoptotic gene Bcl2. JNK activation by eIF2α facilitated photoreceptor cell apoptosis caused by atRAL via caspase-3 activation and DNA damage. Additionally, we demonstrated that eIF2α was activated in neural retina of light-exposed Abca4[-/-]Rdh8[-/-] mice, a model that shows severe defects in atRAL clearance and displays primary features of human dry AMD and STGD1. Of note, inhibition of eIF2α activation by salubrinal effectively ameliorated retinal degeneration and photoreceptor apoptosis in Abca4[-/-]Rdh8[-/-] mice upon light exposure. The results of this study suggest that eIF2α is an important target to develop drug therapies for the treatment of dry AMD and STGD1.},
}
@article {pmid37031737,
year = {2023},
author = {Yañez Ortega, LF and Sanchez Hernández, E and Sánchez-Gómez, J and Menchaca Gutierrez, S},
title = {Correlation between contrast sensitivity and morphological features obtained by OCT in patients with age-related macular degeneration treated with a loading dose of vascular endothelial growth factor inhibitors.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {98},
number = {7},
pages = {377-385},
doi = {10.1016/j.oftale.2023.02.005},
pmid = {37031737},
issn = {2173-5794},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Contrast Sensitivity ; Cross-Sectional Studies ; *Macular Degeneration/diagnostic imaging/drug therapy ; Prospective Studies ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {OBJECTIVE: To determine the correlation between contrast sensitivity and morphological characteristics obtained by Optical Coherence Tomography (OCT) in patients with Age-Related Macular Degeneration treated with a loading dose of vascular endothelial growth factor inhibitors (anti-VEGF).<br><br>DESIGN: This is an ambispective (prospective&#x202f;+&#x202f;retrospective) observational, cross-sectional, and analytical study.<br><br>PARTICIPANTS: All patients over 55 years of age with Age-Related Macular Degeneration who attended the Retina service of the Ophthalmology department and met the inclusion criteria between March-May 2022.<br><br>METHODS: Data collection was carried out by reviewing the records of patients diagnosed with Age-Related Macular Degeneration of the neovascular variety treated with the loading dose of anti-VEGF. OCT studies obtained by Optovue&#xae; iVue80 prior to the application of intravitreal injections of patients who met the inclusion criteria and were currently in the first month after the last dose of anti-VEGF were analyzed. A total of 33 subjects were included, of which 30 continued follow-ups. The subjects underwent a new ophthalmological evaluation and new retinal measurements of the affected eye. Normality tests (Shapiro&#x2012;Wilk) were performed where a nonparametric data distribution was demonstrated.<br><br>RESULTS: A linear regression analysis was performed comparing the logarithmic values of both visual acuity and contrast sensitivity, obtaining a significant relationship between both values after the application of treatment (P&#x202f;=&#x202f;<.0001***). Likewise, correlation was demonstrated between the decrease in contrast sensitivity values and all the characteristics evaluated in the patients' OCT.<br><br>CONCLUSIONS: Antiangiogenesis strategies can lead to better results in global visual function, positively impacting contrast sensitivity.},
}
@article {pmid37030492,
year = {2023},
author = {Romano, F and Cozzi, E and Airaldi, M and Nassisi, M and Viola, F and Aretti, A and Milella, P and Giuffrida, FP and Teo, KCY and Cheung, CMG and Staurenghi, G and Invernizzi, A},
title = {Ten-Year Incidence of Fibrosis and Risk Factors for Its Development in Neovascular Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {252},
number = {},
pages = {170-181},
doi = {10.1016/j.ajo.2023.03.033},
pmid = {37030492},
issn = {1879-1891},
mesh = {Humans ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Incidence ; Cohort Studies ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Fibrosis ; Risk Factors ; *Macular Degeneration/diagnosis/drug therapy/epidemiology ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, multicenter, cohort study.<br><br>METHODS: We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal.<br><br>RESULTS: The mean age at baseline was of 72.1 &#xb1; 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P&#xa0;=&#xa0;.008), higher number of injections (P&#xa0;=&#xa0;.01), and worse baseline visual acuity (VA) (P&#xa0;=&#xa0;.03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001).<br><br>CONCLUSIONS: We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens.},
}
@article {pmid37029733,
year = {2023},
author = {Wang, M and Nguyen, VP and Singh, R and Mossallam, B and Yang, X and Wang, X and Paulus, YM},
title = {Choroidal neovascularization removal with photo-mediated ultrasound therapy.},
journal = {Medical physics},
volume = {50},
number = {6},
pages = {3661-3670},
pmid = {37029733},
issn = {2473-4209},
support = {K08EY027458/GF/NIH HHS/United States ; R41 EY031219/EY/NEI NIH HHS/United States ; K08 EY027458/EY/NEI NIH HHS/United States ; R01EY029489/GF/NIH HHS/United States ; R01 EY029489/EY/NEI NIH HHS/United States ; R41EY031219/GF/NIH HHS/United States ; P30 EY007003/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Rabbits ; Endothelial Growth Factors ; Visual Acuity ; *Choroidal Neovascularization/diagnostic imaging/therapy/etiology ; Retina/diagnostic imaging/pathology ; *Macular Degeneration/pathology ; *Ultrasonic Therapy ; Fluorescein Angiography/adverse effects ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a major cause of irreversible central vision loss. The main reason for lost vision due to AMD is choroidal neovascularization (CNV). In the clinic, current treatments for CNV include photodynamic therapy, laser photocoagulation, and anti-vascular endothelial growth factor (VEGF) therapy.<br><br>PURPOSE: This study evaluates a novel treatment technique combining synchronized nanosecond laser pulses and ultrasound bursts, namely photo-mediated ultrasound therapy (PUT) as a potential treatment method for CNV, for its efficacy and safety in the treatment of CNV via the experiments in a clinically-relevant rabbit model in vivo.<br><br>METHODS: CNV was created by subretinal injection of Matrigel and vascular endothelial growth factor (M&amp;V) in 10 New Zealand white rabbits. Six rabbits were used in the PUT group. In the control groups, two rabbits were treated by laser-only, and two rabbits were treated by ultrasound-only. The treatment efficacy was evaluated through fundus photography and fluorescein angiography (FA) longitudinally for up to 4&#xa0;weeks. Rabbits were sacrificed for histopathology 3 months after treatment to examine the safety of PUT.<br><br>RESULTS: The fluorescein leakage on FA was quantified to longitudinally evaluate treatment outcome. Compared with baseline, the relative intensity index was reduced by 26.57%&#xa0;&#xb1;&#xa0;8.66% at 3 days after treatment, 27.24%&#xa0;&#xb1;&#xa0;6.21% at 1&#xa0;week after treatment, 27.79%&#xa0;&#xb1;&#xa0;2.61% at 2&#xa0;weeks after treatment, and 32.12%&#xa0;&#xb1;&#xa0;3.23% at 4&#xa0;weeks after treatment, all with a statistically significant difference of p&#xa0;<&#xa0;0.01. The comparison between the relative intensity indexes from the two control groups (laser-only treatment and ultrasound-only treatment) did not show any statistically significant difference at all time points. Safety evaluation at 3 months with histopathology demonstrated that the PUT did not result in morphologic changes to the neurosensory retina.<br><br>CONCLUSIONS: This study introduces PUT for the first time for the treatment of CNV. The results demonstrated good efficacy and safety of PUT to treat CNV in a clinically-relevant rabbit model. With a single session of treatment, PUT can safely reduce the leakage of CNV for at least 1 month after treatment.},
}
@article {pmid37029401,
year = {2023},
author = {Liu, TYA and Wang, J and Csaky, KG},
title = {Correlation between hyperreflective foci and visual function testing in eyes with intermediate age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {24},
pmid = {37029401},
issn = {2056-9920},
abstract = {BACKGROUND: To investigate the relationship between intraretinal hyperreflective foci (HRF) and visual function in intermediate age-related macular degeneration (iAMD).<br><br>METHODS: Retrospective, cross-sectional study. iAMD patients underwent spectral domain optical coherence tomography (SD-OCT) imaging and vision function testing: normal luminance best corrected visual acuity (VA), low luminance VA (LLVA), quantitative contrast sensitivity function (qCSF), low luminance qCSF (LLqCSF), and mesopic microperimetry. Each OCT volume was graded for the presence and number of HRF. Each HRF was graded for: separation from the retinal pigment epithelium (RPE), above drusen, and shadowing. Central drusen volume was calculated by the built-in functionality of the commercial OCT software after manual segmentation of the RPE and Bruch's membrane.<br><br>RESULTS: HRF group: 11 eyes; 9 patients; mean age 75.7 years. No-HRF group: 11 eyes; 10 patients; mean age 74.8 years. In linear mixed effect model adjusting for cube-root transformed drusen volume, HRF group showed statistically significant worse VA, LLVA, LLqCSF, and microperimetry. HRF group showed worse cone function, as measured by our pre-defined multicomponent endpoint, incorporating LLVA, LLqCSF and microperimetry (p&#x2009;=&#x2009;0.018). For eyes with HRF, # of HRF did not correlate with any functional measures; however, % of HRF separated from RPE and # of HRF that created shadowing were statistically associated with low luminance deficit (LLD).<br><br>CONCLUSIONS: The association between the presence of HRF and worse cone visual function supports the hypothesis that eyes with HRF have more advanced disease.},
}
@article {pmid37029159,
year = {2023},
author = {Maruyama-Inoue, M and Kitajima, Y and Yanagi, Y and Inoue, T and Kadonosono, K},
title = {Intravitreal anti-vascular endothelial growth factor monotherapy in age-related macular degeneration with submacular hemorrhage.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {5688},
pmid = {37029159},
issn = {2045-2322},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Fundus Oculi ; Intravitreal Injections ; *Macular Degeneration/complications/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Retinal Hemorrhage/complications ; Retrospective Studies ; Treatment Outcome ; Vascular Endothelial Growth Factors/antagonists &amp; inhibitors ; Vitreous Hemorrhage/complications ; },
abstract = {The purpose of this study was to evaluate the 1-year visual outcomes of patients treated with intravitreal aflibercept (IVA) or brolucizumab (IVBr) for submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD). We retrospectively studied 62 treatment-naïve eyes with SMHs exceeding one disc area (DA) secondary to AMD treated with IVA or IVBr. All patients received three monthly intravitreal injections in the loading phase followed by as-needed injections or fixed dosing. If a vitreous hemorrhage (VH) developed during the follow-up period, injections were discontinued and vitrectomy was performed. We evaluated the changes in the best-corrected visual acuity (BCVA) and factors that affected the BCVA improvement and VH development. A VH during treatment developed in five eyes (8.1%) (VH + group), and the mean BCVA worsened from 0.45 to 0.92. The BCVA improved significantly (P = 0.040) in the remaining 57 eyes (VH - group) from 0.42 to 0.36. The development of VHs was associated with significantly (P < 0.001) less VA improvement. Furthermore, large DAs and younger age at baseline were associated significantly (P = 0.010 and 0.046, respectively) with the development of VHs. Both IVA and IVBr appeared to improve functional outcomes in patients with SMH secondary to AMD when VHs did not develop. However, a VH developed in 8.1% of eyes after treatment. Although anti-vascular endothelial growth factor treatments were well-tolerated, for cases with large SMH at baseline, it should be considered that VH may occur during the monotherapy treatment process using IVA or IVBr, and that achieving good visual outcomes may be difficult in some cases.},
}
@article {pmid37028452,
year = {2023},
author = {Tang, Y and Kang, Y and Zhang, X and Cheng, C},
title = {Mesenchymal stem cell exosomes as nanotherapeutics for dry age-related macular degeneration.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {357},
number = {},
pages = {356-370},
doi = {10.1016/j.jconrel.2023.04.003},
pmid = {37028452},
issn = {1873-4995},
mesh = {Humans ; Kelch-Like ECH-Associated Protein 1/metabolism ; NF-E2-Related Factor 2/metabolism/pharmacology/therapeutic use ; *Exosomes/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; *Macular Degeneration/drug therapy ; *Mesenchymal Stem Cells/metabolism ; Retinal Pigment Epithelium ; },
abstract = {Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a major factor in the pathogenesis of dry age-related macular degeneration (AMD). Although the therapeutic effect of mesenchymal stem cell (MSC) exosomes on dry AMD has been preliminarily discussed, the underlying mechanism has yet to be reported. Here, we demonstrate that MSC exosomes, acting as a nanodrug, can effectively reduce the incidence of dry AMD by regulating Nrf2/Keap1 signaling pathway. In the in vitro study, MSC exosomes relieved the damage of ARPE-19 cells, suppressed the activity of lactate dehydrogenase (LDH), decreased the level of reactive oxygen species (ROS) and upregulated the activity of superoxide dismutase (SOD). In the in vivo study, MSC exosomes were administered via intravitreal injection. MSC exosomes effectively protected RPE layer, photoreceptor outer segment/inner segment (OS/IS) layer and outer nuclear layer (ONL) from NaIO3-induced damage. Western blotting results showed that the ratio of Bcl-2/Bax was increased after pre-administration of MSC exosomes in both in vitro and in vivo studies. Moreover, MSC exosomes were found to upregulate the expressions of Nrf2, P-Nrf2, Keap1 and HO-1, while the antioxidant effect of MSC exosomes was blocked by ML385 (a Nrf2 inhibitor). Besides, immunofluorescence results showed that MSC exosomes upregulated the expression of P-Nrf2 in the nucleus compared to the oxidant group. These results indicate that MSC exosomes protect RPE cells from oxidative damage by regulating Nrf2/Kepa1 signaling pathway. In conclusion, MSC exosomes are promising nanotherapeutics for the treatment of dry AMD.},
}
@article {pmid37027819,
year = {2023},
author = {Benlahbib, M and Cohen, SY and Torrell, N and Colantuono, D and Crincoli, E and Amoroso, F and Semoun, O and Jung, C and Souied, EH},
title = {PHOTOBIOMODULATION THERAPY FOR LARGE SOFT DRUSEN AND DRUSENOID PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: A Single-Center Prospective Pilot Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {8},
pages = {1246-1254},
doi = {10.1097/IAE.0000000000003805},
pmid = {37027819},
issn = {1539-2864},
mesh = {Humans ; Pilot Projects ; *Low-Level Light Therapy ; Prospective Studies ; Quality of Life ; *Macular Degeneration/complications ; *Retinal Drusen/complications ; *Retinal Detachment/complications ; *Geographic Atrophy/complications ; Tomography, Optical Coherence ; Follow-Up Studies ; },
abstract = {PURPOSE: To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial detachment associated with dry age-related macular degeneration.<br><br>METHOD: Twenty eyes with large soft drusen and/or drusenoid pigment epithelial detachment age-related macular degeneration were included and treated using the LumiThera Valeda Light Delivery System. All patients underwent two treatments per week for 5 weeks. Outcome measures included best-corrected visual acuity, microperimetry-scotopic testing, drusen volume, central drusen thickness, and quality of life score at baseline and month 6 (M6) follow-up. Data of best-corrected visual acuity, drusen volume, and central drusen thickness were also recorded at week 5 (W5).<br><br>RESULTS: Best-corrected visual acuity significantly improved at M6 with a mean score gain of 5.5 letters (P = 0.007). Retinal sensitivity decreased by 0.1 dB (P = 0.17). The mean fixation stability increased by 0.45% (P = 0.72). Drusen volume decreased by 0.11 mm 3 (P = 0.03). Central drusen thickness was reduced by a mean of 17.05 &#xb5; m (P = 0.01). Geographic atrophy area increased by 0.06 mm 2 (P = 0.01) over a 6-month follow-up, and quality of life score increased by 3,07 points on average (P = 0.05). One patient presented a drusenoid pigment epithelial detachment rupture at M6 after PBM treatment.<br><br>CONCLUSION: The visual and anatomical improvements in our patients support previous reports on PBM. PBM may provide a valid therapeutic option for large soft drusen and drusenoid pigment epithelial detachment age-related macular degeneration and may potentially slow the natural course of the disease.},
}
@article {pmid37026258,
year = {2023},
author = {Shetty, R and Joshi, PD and Mahendran, K and Jayadev, C and Das, D},
title = {Resveratrol for dry eye disease - Hope or Hype?.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {4},
pages = {1270-1275},
pmid = {37026258},
issn = {1998-3689},
mesh = {Infant, Newborn ; Humans ; Resveratrol/therapeutic use ; *Quality of Life ; *Dry Eye Syndromes/diagnosis ; Tears ; Anti-Inflammatory Agents/therapeutic use ; },
abstract = {Dry eye disease (DED) is a multifactorial and common ophthalmic disease that has a tremendous effect on the quality of life. It is now becoming a public health concern because of our changing lifestyle and environment. The current treatment modalities, artificial tear substitutes, and anti-inflammatory therapy are directed at dry eye symptoms. One of the major drivers for DED is oxidative stress, and the polyphenol group of natural compounds has the potential to reduce the same. Resveratrol, widely found in the skin of grapes and nuts, has antioxidative and anti-inflammatory properties. It has been shown to have beneficial effects in glaucoma, age-related macular degeneration, retinopathy of prematurity, uveitis, and diabetic retinopathy. Studies have also explored the beneficial effects of resveratrol in DED, making it as a promising therapeutic molecule. Resveratrol has not yet reached clinical application because of difficulty in deliverability and low bioavailability. In this review, we explore the potential of resveratrol in DED treatment based on various in vitro and in vivo studies.},
}
@article {pmid37026243,
year = {2023},
author = {Venkatesh, R and Jayadev, C and Mangla, R and Chitturi, SP and Mohan, S and Ratra, D},
title = {Ocular surface changes following vitreoretinal procedures.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {4},
pages = {1123-1126},
pmid = {37026243},
issn = {1998-3689},
mesh = {Humans ; Aged ; *Quality of Life ; Eye ; Vision, Ocular ; *Dry Eye Syndromes/diagnosis ; Vision Disorders ; },
abstract = {Dry eye disease (DED) can lead to ocular discomfort as well as visual disturbances. Older adults are more likely to develop DED. They are also more likely to develop retinal diseases such as diabetic retinopathy and age-related macular degeneration, which may require vitreoretinal surgeries, lasers, and intravitreal injections. Posterior segment surgery may cause or worsen existing dry eye symptoms, albeit temporarily. Despite good anatomic and functional outcomes, ocular surface dysfunction can have a significant impact on the quality of life, lowering a patient's satisfaction with the retinal treatment. Preexisting DED, intraoperative tissue handling, and postoperative treatment may all contribute to the severity of ocular surface dysfunction. In this article, we have reviewed all relevant studies on the development of ocular surface changes and DED, as well as the impact of vitreoretinal surgeries and procedures on the ocular surface.},
}
@article {pmid37025170,
year = {2023},
author = {Wakabayashi, T and Naito, H},
title = {Cellular heterogeneity and stem cells of vascular endothelial cells in blood vessel formation and homeostasis: Insights from single-cell RNA sequencing.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1146399},
pmid = {37025170},
issn = {2296-634X},
abstract = {Vascular endothelial cells (ECs) that constitute the inner surface of blood vessels are essential for new vessel formation and organ homeostasis. ECs display remarkable phenotypic heterogeneity across different organs and the vascular tree during angiogenesis and homeostasis. Recent advances in single cell RNA sequencing (scRNA-seq) technologies have allowed a new understanding of EC heterogeneity in both mice and humans. In particular, scRNA-seq has identified new molecular signatures for arterial, venous and capillary ECs in different organs, as well as previously unrecognized specialized EC subtypes, such as the aerocytes localized in the alveolar capillaries of the lung. scRNA-seq has also revealed the gene expression profiles of specialized tissue-resident EC subtypes that are capable of clonal expansion and contribute to adult angiogenesis, a process of new vessel formation from the pre-existing vasculature. These specialized tissue-resident ECs have been identified in various different mouse tissues, including aortic endothelium, liver, heart, lung, skin, skeletal muscle, retina, choroid, and brain. Transcription factors and signaling pathways have also been identified in the specialized tissue-resident ECs that control angiogenesis. Furthermore, scRNA-seq has also documented responses of ECs in diseases such as cancer, age-related macular degeneration, Alzheimer's disease, atherosclerosis, and myocardial infarction. These new findings revealed by scRNA-seq have the potential to provide new therapeutic targets for different diseases associated with blood vessels. In this article, we summarize recent advances in the understanding of the vascular endothelial cell heterogeneity and endothelial stem cells associated with angiogenesis and homeostasis in mice and humans, and we discuss future prospects for the application of scRNA-seq technology.},
}
@article {pmid37024576,
year = {2023},
author = {Moon, S and Lee, Y and Hwang, J and Kim, CG and Kim, JW and Yoon, WT and Kim, JH},
title = {Prediction of anti-vascular endothelial growth factor agent-specific treatment outcomes in neovascular age-related macular degeneration using a generative adversarial network.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {5639},
pmid = {37024576},
issn = {2045-2322},
mesh = {Humans ; *Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Bevacizumab/therapeutic use ; Retrospective Studies ; Artificial Intelligence ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Treatment Outcome ; Vascular Endothelial Growth Factors ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {To develop an artificial intelligence (AI) model that predicts anti-vascular endothelial growth factor (VEGF) agent-specific anatomical treatment outcomes in neovascular age-related macular degeneration (AMD), thereby assisting clinicians in selecting the most suitable anti-VEGF agent for each patient. This retrospective study included patients diagnosed with neovascular AMD who received three loading injections of either ranibizumab or aflibercept. Training was performed using optical coherence tomography (OCT) images with an attention generative adversarial network (GAN) model. To test the performance of the AI model, the sensitivity and specificity to predict the presence of retinal fluid after treatment were calculated for the AI model, an experienced (Examiner 1), and a less experienced (Examiner 2) human examiners. A total of 1684 OCT images from 842 patients (419 treated with ranibizumab and 423 treated with aflibercept) were used as the training set. Testing was performed using images from 98 patients. In patients treated with ranibizumab, the sensitivity and specificity, respectively, were 0.615 and 0.667 for the AI model, 0.385 and 0.861 for Examiner 1, and 0.231 and 0.806 for Examiner 2. In patients treated with aflibercept, the sensitivity and specificity, respectively, were 0.857 and 0.881 for the AI model, 0.429 and 0.976 for Examiner 1, and 0.429 and 0.857 for Examiner 2. In 18.5% of cases, the fluid status of synthetic posttreatment images differed between ranibizumab and aflibercept. The AI model using GAN might predict anti-VEGF agent-specific short-term treatment outcomes with relatively higher sensitivity than human examiners. Additionally, there was a difference in the efficacy in fluid resolution between the anti-VEGF agents. These results suggest the potential of AI in personalized medicine for patients with neovascular AMD.},
}
@article {pmid37024045,
year = {2023},
author = {Douglas, VP and Douglas, KAA and Iannaccone, A},
title = {Microbiome and Inherited Retinal Degenerations.},
journal = {The American journal of pathology},
volume = {193},
number = {11},
pages = {1669-1674},
doi = {10.1016/j.ajpath.2023.03.005},
pmid = {37024045},
issn = {1525-2191},
abstract = {Inherited retinal degenerations (IRDs) represent a genetically and clinically heterogeneous group of progressive and visually debilitating disorders that can lead to irreversible visual loss. Our understanding of IRD pathogenesis at both the genetic and cellular levels has increased tremendously over the past two decades, but the exact pathogenic mechanisms remain incompletely understood. Enhanced understanding of the pathophysiology of these diseases can result in new treatment targets. Alterations in the human gut microbiome play a key role in the pathogenesis of many ocular and nonocular diseases, such as age-related macular degeneration, neurologic and metabolic disorders, and autoimmune conditions. The gut microbiome regulates the susceptibility of mice to develop experimental autoimmune uveitis, a model for autoimmune disease of the posterior portion of the eye elicited by the systemic response to retinal antigens. Because of the mounting evidence in favor of a role for local and systemic inflammatory and autoimmune-mediated components to IRD pathogenesis, this review presents the current knowledge of gut microbiome in IRDs and discusses the association between possible changes in gut microbiome and pathogenesis of these diseases, with special attention to their possible contribution to the inflammatory underpinnings of IRDs.},
}
@article {pmid37023894,
year = {2023},
author = {Bachmeier, I and Armendariz, BG and Yu, S and Jäger, RJ and Ebneter, A and Glittenberg, C and Pauleikhoff, D and Sadda, SR and Chakravarthy, U and Fauser, S},
title = {Fibrosis in neovascular age-related macular degeneration: A review of definitions based on clinical imaging.},
journal = {Survey of ophthalmology},
volume = {68},
number = {5},
pages = {835-848},
doi = {10.1016/j.survophthal.2023.03.004},
pmid = {37023894},
issn = {1879-3304},
mesh = {Humans ; Visual Acuity ; Retina/diagnostic imaging/pathology ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; Fibrosis ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Despite the success of antiangiogenic therapy in controlling exudation in neovascular age-related macular degeneration (nAMD), the involvement of the outer retina in fibrosis results in gradual vision loss over time. The development of drugs that prevent or ameliorate fibrosis in nAMD requires that it is accurately detected and quantified with reliable endpoints and identification of robust biomarkers. Achievement of such an aim is currently challenging due to the lack of a consensus definition of fibrosis in nAMD. As a first step towards the establishment of a clear definition of fibrosis, we provide an extensive overview of the imaging modalities and criteria used to characterize fibrosis in nAMD. We observed variety in the selection of individual and combinations of imaging modalities, and criteria for detection. We also observed heterogeneity in classification systems and severity scales for fibrosis. The most commonly used imaging modalities were color fundus photography, fluorescein angiography and optical coherence tomography (OCT). A multimodal approach was frequently utilized. Our review suggests that OCT offers a more detailed, objective and sensitive characterization than color fundus photography/fluorescein angiography. Thus, we recommend it as a primary modality for fibrosis evaluation. This review provides a basis for future discussions to reach a consensus definition using standardized terms based on a detailed characterization of fibrosis, its presence and evolution, and taking into consideration impact on visual function. Achieving this goal is of paramount importance for the development of antifibrotic therapies.},
}
@article {pmid37023082,
year = {2023},
author = {Leng, X and Shi, R and Wu, Y and Zhu, S and Cai, X and Lu, X and Liu, R},
title = {Deep learning for detection of age-related macular degeneration: A systematic review and meta-analysis of diagnostic test accuracy studies.},
journal = {PloS one},
volume = {18},
number = {4},
pages = {e0284060},
pmid = {37023082},
issn = {1932-6203},
mesh = {Humans ; *Deep Learning ; Neural Networks, Computer ; Algorithms ; *Macular Degeneration/diagnosis ; Sensitivity and Specificity ; Diagnostic Tests, Routine ; },
abstract = {OBJECTIVE: To evaluate the diagnostic accuracy of deep learning algorithms to identify age-related macular degeneration and to explore factors impacting the results for future model training.<br><br>METHODS: Diagnostic accuracy studies published in PubMed, EMBASE, the Cochrane Library, and ClinicalTrails.gov before 11 August 2022 which employed deep learning for age-related macular degeneration detection were identified and extracted by two independent researchers. Sensitivity analysis, subgroup, and meta-regression were performed by Review Manager 5.4.1, Meta-disc 1.4, and Stata 16.0. The risk of bias was assessed using QUADAS-2. The review was registered (PROSPERO CRD42022352753).<br><br>RESULTS: The pooled sensitivity and specificity in this meta-analysis were 94% (P = 0, 95% CI 0.94-0.94, I2 = 99.7%) and 97% (P = 0, 95% CI 0.97-0.97, I2 = 99.6%), respectively. The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the area under the curve value were 21.77(95% CI 15.49-30.59), 0.06 (95% CI 0.04-0.09), 342.41 (95% CI 210.31-557.49), and 0.9925, respectively. Meta-regression indicated that types of AMD (P = 0.1882, RDOR = 36.03) and layers of the network (P = 0.4878, RDOR = 0.74) contributed to the heterogeneity.<br><br>CONCLUSIONS: Convolutional neural networks are mostly adopted deep learning algorithms in age-related macular degeneration detection. Convolutional neural networks, especially ResNets, are effective in detecting age-related macular degeneration with high diagnostic accuracy. Types of age-related macular degeneration and layers of the network are the two essential factors that impact the model training process. Proper layers of the network will make the model more reliable. More datasets established by new diagnostic methods will be used to train deep learning models in the future, which will benefit for fundus application screening, long-range medical treatment, and reducing the workload of physicians.},
}
@article {pmid37022267,
year = {2023},
author = {Shen, Y and Li, J and Zhu, W and Yu, K and Wang, M and Peng, Y and Zhou, Y and Guan, L and Chen, X},
title = {Graph Attention U-Net for Retinal Layer Surface Detection and Choroid Neovascularization Segmentation in OCT Images.},
journal = {IEEE transactions on medical imaging},
volume = {42},
number = {11},
pages = {3140-3154},
doi = {10.1109/TMI.2023.3240757},
pmid = {37022267},
issn = {1558-254X},
mesh = {Humans ; Tomography, Optical Coherence/methods ; Retina/diagnostic imaging ; *Choroidal Neovascularization/diagnostic imaging/pathology ; *Macular Degeneration/diagnostic imaging ; Diagnostic Techniques, Ophthalmological ; },
abstract = {Choroidal neovascularization (CNV) is a typical symptom of age-related macular degeneration (AMD) and is one of the leading causes for blindness. Accurate segmentation of CNV and detection of retinal layers are critical for eye disease diagnosis and monitoring. In this paper, we propose a novel graph attention U-Net (GA-UNet) for retinal layer surface detection and CNV segmentation in optical coherence tomography (OCT) images. Due to retinal layer deformation caused by CNV, it is challenging for existing models to segment CNV and detect retinal layer surfaces with the correct topological order. We propose two novel modules to address the challenge. The first module is a graph attention encoder (GAE) in a U-Net model that automatically integrates topological and pathological knowledge of retinal layers into the U-Net structure to achieve effective feature embedding. The second module is a graph decorrelation module (GDM) that takes reconstructed features by the decoder of the U-Net as inputs, it then decorrelates and removes information unrelated to retinal layer for improved retinal layer surface detection. In addition, we propose a new loss function to maintain the correct topological order of retinal layers and the continuity of their boundaries. The proposed model learns graph attention maps automatically during training and performs retinal layer surface detection and CNV segmentation simultaneously with the attention maps during inference. We evaluated the proposed model on our private AMD dataset and another public dataset. Experiment results show that the proposed model outperformed the competing methods for retinal layer surface detection and CNV segmentation and achieved new state of the arts on the datasets.},
}
@article {pmid37020339,
year = {2023},
author = {},
title = {Pegcetacoplan (Syfovre) for geographic atrophy in age-related macular degeneration.},
journal = {The Medical letter on drugs and therapeutics},
volume = {65},
number = {1673},
pages = {49-50},
doi = {10.58347/tml.2023.1673a},
pmid = {37020339},
issn = {1523-2859},
mesh = {Humans ; *Geographic Atrophy ; *Macular Degeneration ; Peptides, Cyclic ; },
}
@article {pmid37019522,
year = {2023},
author = {Repka, MX},
title = {International Classification of Disease: Required Specificity when Coding for Age-related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {4},
pages = {287-288},
doi = {10.1016/j.oret.2023.01.006},
pmid = {37019522},
issn = {2468-6530},
mesh = {Humans ; *International Classification of Diseases ; *Macular Degeneration ; },
}
@article {pmid37019186,
year = {2023},
author = {Shin, CY and Lee, S and Jin, HL and Fei, X and Kang, SW and Seo, SY and Jeong, KW},
title = {A small molecule compound that inhibits blue light-induced retinal damage via activation of autophagy.},
journal = {Biochemical pharmacology},
volume = {211},
number = {},
pages = {115534},
doi = {10.1016/j.bcp.2023.115534},
pmid = {37019186},
issn = {1873-2968},
mesh = {Humans ; Mice ; Animals ; *Retina ; *Light ; Retinal Pigment Epithelium/metabolism/radiation effects ; Cell Line ; Autophagy/physiology ; },
abstract = {Dry age-related macular degeneration (AMD) is a type of disease that causes visual impairment due to changes in the macula located in the center of the retina. The accumulation of drusen under the retina is also a characteristic of dry AMD. In this study, we identified a compound (JS-017) that can potentially degrade N-retinylidene-N-retinylethanolamine (A2E), one of the components of lipofuscin, using fluorescence-based screening, which measures A2E degradation in human retinal pigment epithelial cells. JS-017 effectively degraded A2E in ARPE-19 cells and consequently suppressed the activation of the NF-κB signaling pathway and expression of inflammatory and apoptosis genes induced by blue light (BL). Mechanistically, JS-017 induced LC3-II formation and improved autophagic flux in ARPE-19 cells. Additionally, the A2E degradation activity of JS-017 was found to be decreased in autophagy-related 5 protein-depleted ARPE-19 cells, suggesting that autophagy was required for A2E degradation mediated by JS-017. Finally, JS-017 exhibited an improvement in BL-induced retinal damage measured through fundus examination in an in vivo retinal degeneration mouse model. The thickness of the outer nuclear layer and inner/external segments, which was decreased upon exposure to BL irradiation, was also restored upon JS-017 treatment. Altogether, we demonstrated that JS-017 protected human retinal pigment epithelium (RPE) cells from A2E and BL-induced damage by degrading A2E via the activation of autophagy. The results suggest the feasibility of a novel A2E-degrading small molecule as a therapeutic agent for retinal degenerative diseases.},
}
@article {pmid37017569,
year = {2023},
author = {Li, R and Liu, J and Yi, P and Yang, X and Chen, J and Zhao, C and Liao, X and Wang, X and Xu, Z and Lu, H and Li, H and Zhang, Z and Liu, X and Xiang, J and Hu, K and Qi, H and Yu, J and Yang, P and Hou, S},
title = {Integrative Single-Cell Transcriptomics and Epigenomics Mapping of the Fetal Retina Developmental Dynamics.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {10},
number = {16},
pages = {e2206623},
pmid = {37017569},
issn = {2198-3844},
support = {82070951//National Natural Science Foundation Project of China/ ; 82271078//National Natural Science Foundation Project of China/ ; CXQT19015//Innovative Research Group Project of Chongqing Education Commission/ ; cx2018010//Innovation Supporting Plan of Overseas Study of Chongqing/ ; //National Key Clinical Specialties Construction Program of China/ ; //Chongqing Branch of National Clinical Research Center for Ocular Diseases/ ; 2008CA5003//Chongqing Key Laboratory of Ophthalmology/ ; w0047//Program for Youth Innovation in Future Medicine, Chongqing Medical University/ ; },
mesh = {Humans ; *Transcriptome/genetics ; *Epigenomics ; Retina/metabolism ; Neurogenesis ; Chromatin/genetics ; },
abstract = {The underlying mechanisms that determine gene expression and chromatin accessibility in retinogenesis are poorly understood. Herein, single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing are performed on human embryonic eye samples obtained 9-26 weeks after conception to explore the heterogeneity of retinal progenitor cells (RPCs) and neurogenic RPCs. The differentiation trajectory from RPCs to 7 major types of retinal cells are verified. Subsequently, diverse lineage-determining transcription factors are identified and their gene regulatory networks are refined at the transcriptomic and epigenomic levels. Treatment of retinospheres, with the inhibitor of RE1 silencing transcription factor, X5050, induces more neurogenesis with the regular arrangement, and a decrease in Müller glial cells. The signatures of major retinal cells and their correlation with pathogenic genes associated with multiple ocular diseases, including uveitis and age-related macular degeneration are also described. A framework for the integrated exploration of single-cell developmental dynamics of the human primary retina is provided.},
}
@article {pmid37016576,
year = {2023},
author = {Qi, X and Francelin, C and Mitter, S and Boye, SL and Gu, H and Quigley, J and Grant, MB and Boulton, ME},
title = {β-secretase 1 overexpression by AAV-mediated gene delivery prevents retina degeneration in a mouse model of age-related macular degeneration.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {31},
number = {7},
pages = {2042-2055},
pmid = {37016576},
issn = {1525-0024},
support = {R01 EY012601/EY/NEI NIH HHS/United States ; R01 EY032753/EY/NEI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY025383/EY/NEI NIH HHS/United States ; R01 EY028037/EY/NEI NIH HHS/United States ; R01 EY028858/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; Mice ; *Amyloid Precursor Protein Secretases/genetics/metabolism ; Aspartic Acid Endopeptidases/genetics ; *Macular Degeneration/genetics/prevention &amp; control ; Retina/metabolism ; Retinal Pigment Epithelium/metabolism ; },
abstract = {We reported previously that β-site amyloid precursor protein cleaving enzyme (BACE1) is strongly expressed in the normal retina and that BACE1[-/-] mice develop pathological phenotypes associated with age-related macular degeneration (AMD). BACE1 expression is increased within the neural retina and retinal pigment epithelium (RPE) in AMD donor eyes suggesting that increased BACE1 is compensatory. We observed that AAV-mediated BACE1 overexpression in the RPE was maintained up to 6 months after AAV1-BACE1 administration. No significant changes in normal mouse visual function or retinal morphology were observed with low-dose vector while the high-dose vector demonstrated some early pathology which regressed with time. No increase in β-amyloid was observed. BACE1 overexpression in the RPE of the superoxide dismutase 2 knockdown (SOD2 KD) mouse, which exhibits an AMD-like phenotype, prevented loss of retinal function and retinal pathology, and this was sustained out to 6 months. Furthermore, BACE1 overexpression was able to inhibit oxidative stress, microglial changes, and loss of RPE tight junction integrity (all features of AMD) in SOD2 KD mice. In conclusion, BACE1 plays a key role in retina/RPE homeostasis, and BACE1 overexpression offers a novel therapeutic target in the treatment of AMD.},
}
@article {pmid37013151,
year = {2023},
author = {Kusumawardhani, SI},
title = {Posterior Vitreous Detachment and Its Role in the Evolution of Dry to Wet Age Related Macular Degeneration [Letter].},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {991-992},
pmid = {37013151},
issn = {1177-5467},
}
@article {pmid37009540,
year = {2022},
author = {Hua, HU and Rayess, N and Li, AS and Do, D and Rahimy, E},
title = {Quality, Readability, and Accessibility of Online Content From a Google Search of "Macular Degeneration": Critical Analysis.},
journal = {Journal of vitreoretinal diseases},
volume = {6},
number = {6},
pages = {437-442},
pmid = {37009540},
issn = {2474-1272},
abstract = {PURPOSE: This work aims to assess the quality, accountability, readability, accessibility, and presence of Spanish translation in online material through a Google search of "macular degeneration".<br><br>METHODS: In this retrospective cross-sectional analysis of website results from a Google search of "macular degeneration", the quality and accountability for each website were assessed using the DISCERN criteria and the Health on the Net Foundation Code of Conduct (HONcode) principles. All 31 sites were independently graded by 2 ophthalmologists. Readability was evaluated using an online tool. The presence of accessibility features on the website and Spanish translation was recorded. The primary outcome measure was the DISCERN and HONcode quality and accountability scores of each website. Secondary outcome measures included the readability, accessibility, and presence of Spanish translation.<br><br>RESULTS: The mean&#x2009;&#xb1;&#x2009;SD of each criterion across all 15 DISCERN questions was 2.761&#x2009;&#xb1;&#x2009;0.666 (out of 5). The mean HONcode score for all websites was 7.355&#x2009;&#xb1;&#x2009;3.123. The mean consensus reading grade level was 10.258&#x2009;&#xb1;&#x2009;2.49. There were no statistically significant differences in any score between the top 5 websites and the bottom 26 websites evaluated. Accessibility was available on 10 of 31 websites. Spanish translation was available on 10 of 31 websites.<br><br>CONCLUSIONS: The top 5 websites that appeared on a Google search did not have better quality or readability of online content. Improving quality, accountability, and readability can help improve patients' health literacy regarding macular degeneration.},
}
@article {pmid37009453,
year = {2023},
author = {Rossi, SL and Subramanian, P and Bovenkamp, DE},
title = {The future is precision medicine-guided diagnoses, preventions and treatments for neurodegenerative diseases.},
journal = {Frontiers in aging neuroscience},
volume = {15},
number = {},
pages = {1128619},
pmid = {37009453},
issn = {1663-4365},
}
@article {pmid37008547,
year = {2022},
author = {Foulsham, W and Chien, J and Lenis, TL and Papakostas, TD},
title = {Optical Coherence Tomography Angiography: Clinical Utility and Future Directions.},
journal = {Journal of vitreoretinal diseases},
volume = {6},
number = {3},
pages = {229-242},
pmid = {37008547},
issn = {2474-1272},
abstract = {PURPOSE: This work aims to review the principles of optical coherence tomography angiography (OCTA), to survey its clinical utility, and to highlight the strengths of this technology as well as barriers to adoption.<br><br>METHODS: A literature review with editorial discussion of the current applications for OCTA is presented.<br><br>RESULTS: There have been recent advances in multiple domains in OCTA imaging, including devices, algorithms, and new observations pertaining to a range of pathologies. New devices have improved the scanning speed, signal-to-noise ratio, and spatial resolution and offer an increased field of view. New algorithms have been proposed to optimize image processing and reduce artifacts. Numerous studies employing OCTA have been published describing changes to the microvasculature in diabetic retinopathy, age-related macular degeneration, central serous chorioretinopathy, retinal vein occlusion, and uveitis.<br><br>CONCLUSIONS: OCTA provides noninvasive, high-resolution volumetric scans of the retinal and choroidal vasculature. OCTA can provide valuable data to augment traditional dye-based angiography in a range of chorioretinal diseases.},
}
@article {pmid37008402,
year = {2023},
author = {Heier, JS and Ho, AC and Boyer, DS and Csaky, K and Vitti, R and Perlee, L and Chu, KW and Asmus, F and Leal, S and Zeitz, O and Cheng, Y and Schmelter, T and Brown, DM},
title = {Intravitreal Nesvacumab (Anti-Angiopoietin-2) Plus Aflibercept in Neovascular AMD: Phase 2 ONYX Randomized Trial.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {1},
pages = {8-15},
pmid = {37008402},
issn = {2474-1272},
abstract = {PURPOSE: To compare intravitreal nesvacumab (anti-angiopoietin-2) + aflibercept vs intravitreal aflibercept injection (IAI) in neovascular age-related macular degeneration (nAMD).<br><br>METHODS: Eyes were randomized (1:2:3) to nesvacumab 3 mg&#x2009;+&#x2009;aflibercept 2 mg (LD combo), nesvacumab 6 mg&#x2009;+&#x2009;aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, week 4, and week 8. The LD combo was continued every 8 weeks (q8w). At week 12, the HD combo was re-randomized to q8w or every 12 weeks (q12w) and IAI was re-randomized to q8w, q12w, or HD combo q8w through week 32.<br><br>RESULTS: The study comprised 365 eyes. At week 12, the mean best-corrected visual acuity (BCVA) gains from baseline were similar in the LD combo group, HD combo group, and IAI group (5.2 letters, 5.6 letters, and 5.4 letters, respectively); the mean central subfield thickness (CST) reductions were similar (182.2 &#xb5;m, 200.0 &#xb5;m, and 178.6 &#xb5;m, respectively). The mean changes in BCVA and CST through week 36 were similar across groups. At week 12, complete retinal fluid resolution was observed in 49.1% (LD combo), 50.8% (HD combo), and 43.6% (IAI) of eyes; the proportions with a CST of 300 &#x3bc;m or less were similar across groups. Numerical trends at week 32 toward complete retinal fluid resolution with combination treatment were not maintained at week 36. Serious ocular adverse events were infrequent and comparable across groups.<br><br>CONCLUSIONS: In nAMD, nesvacumab&#x2009;+&#x2009;aflibercept showed no additional BCVA or CST benefit over IAI monotherapy.},
}
@article {pmid37008399,
year = {2023},
author = {Song, W and Kanyo, E and Bastian, R and Singh, RP and Rachitskaya, AV},
title = {Visual Acuity in Patients Requiring Intravitreal Injections: Short-Term and Long-Term Effects of Delay in Care.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {1},
pages = {20-26},
pmid = {37008399},
issn = {2474-1272},
abstract = {Purpose: To assess the short-term and long-term effects of a delay in care on visual acuity (VA) in patients requiring intravitreal injections. Methods: This retrospective cohort study comprised patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) receiving intravitreal injections. The visual and anatomic outcomes at the next completed visit and at the 1-year follow-up were studied. Results: Of 1172 patients, 38% had a delay in care (mean 5.7 weeks). Compared with baseline, these patients lost VA (Early Treatment Diabetic Retinopathy Study letters) (mean -2.13 ± 0.49 SE) in the short-term (P = .0003) and had a thicker central subfield. Patients with no delay in care had a net VA gain (0.97 ± 0.39) (P = .0067). There was no difference in VA between 1 year and the baseline in either group. Long term, patients with nAMD in both groups had VA loss (no delay in care: -1.76 ± 0.60; delayed care: -2.44 ± 0.78) (P = .0005 and P = .0114, respectively). Patients with DME and no delay in care maintained gains in vision (4.68 ± 1.86) but those with delayed care did not (1.72 ± 2.24) (P = .0202 and P = .3756, respectively). In both groups, patients with RVO had no significant difference in vision from baseline. Conclusions: In patients requiring intravitreal injections, a delay in care of 5.7 weeks affected vision outcomes in the short term but not the long term.},
}
@article {pmid37008398,
year = {2023},
author = {Greenberg, JR and Kim, BY and Brady, CJ and Millay, RH and Raut, R},
title = {Optical Coherence Tomography Angiography for Detecting Nonexudative Macular Neovascularization in Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {1},
pages = {16-19},
pmid = {37008398},
issn = {2474-1272},
abstract = {PURPOSE: To compare the efficacy of optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) for detecting nonexudative macular neovascularization (MNV) in age-related macular degeneration (AMD).<br><br>METHODS: In this prospective study, patients with a new diagnosis of exudative AMD in 1 eye were imaged using OCTA, fluorescein angiography (FA), and ICGA in both eyes. The rates at which these imaging modalities detected nonexudative MNV in the nonexudative fellow eye were then compared.<br><br>RESULTS: This study comprised 41 eyes with a mean follow-up was 14 months. Nonexudative MNV was found in 3 eyes using OCTA and ICGA. No MNV exudation was detected on FA or structural OCT. One of 3 eyes with MNV progressed to exudative disease 6 months after the initial visit. During the follow-up, 5 of the 38 eyes without MNV developed exudation at 4 to 18 months.<br><br>CONCLUSIONS: OCTA is similarly effective as ICGA at detecting nonexudative MNV patterns.},
}
@article {pmid37008392,
year = {2023},
author = {Szelog, JT and Shah, NS and Camejo, MD},
title = {Cystoid Macular Edema Arising 10 Years After Cessation of Pentosan Polysulfate Sodium Successfully Treated With Bevacizumab.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {1},
pages = {83-86},
pmid = {37008392},
issn = {2474-1272},
abstract = {PURPOSE: To describe a patient initially diagnosed with age-related macular degeneration (AMD) who was ultimately determined to have progressing pentosan polysulfate sodium (PPS)-associated maculopathy leading to secondary cystoid macular edema (CME) 10 years after cessation of PPS.<br><br>METHODS: An interventional case report is presented.<br><br>RESULTS: A 57-year-old woman diagnosed with AMD presented with unilateral worsening vision and metamorphopsia from CME. A detailed history showed a 3-year course of PPS, which had been discontinued 10 years previously. This led to the diagnosis of PPS-associated maculopathy. After topical NSAID and corticosteroid treatment failed, intravitreal bevacizumab resolved the symptoms. CME developed in the fellow eye 5 months later and also responded to bevacizumab.<br><br>CONCLUSIONS: This case emphasizes the importance of a thorough review of past medication and medical histories in patients with pigmentary retinopathy and supports the use of antivascular endothelial growth factor therapy as an option to treat CME secondary to PPS-associated maculopathy.},
}
@article {pmid37007646,
year = {2023},
author = {Mullany, S and Diaz-Torres, S and Schmidt, JM and Thomson, D and Qassim, A and Marshall, HN and Knight, LSW and Berry, EC and Kolovos, A and Dimasi, D and Lake, S and Mills, RA and Landers, J and Mitchell, P and Healey, PR and Commerford, T and Klebe, S and Souzeau, E and Hassall, MM and MacGregor, S and Gharahkhani, P and Siggs, OM and Craig, JE},
title = {No Strong Association between the Apolipoprotein E E4 Allele and Glaucoma: A Multicohort Study.},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100287},
pmid = {37007646},
issn = {2666-9145},
support = {/WT_/Wellcome Trust/United Kingdom ; },
abstract = {PURPOSE: To elucidate a potential association between the apolipoprotein E (APOE) E4 allele and glaucoma prevalence in large cohorts.<br><br>DESIGN: A cross-sectional analysis of baseline and prospectively collected cohort data.<br><br>PARTICIPANTS: UK Biobank (UKBB) participants of genetically determined European ancestry (n&#xa0;= 438 711). Replication analyses were performed using clinical and genotyping data collected from European participants recruited to the Canadian Longitudinal Study of Aging (CLSA; n&#xa0;= 18 199), the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG; n&#xa0;= 1970), and the Blue Mountains Eye Study (BMES; n&#xa0;= 2440).<br><br>METHODS: Apolipoprotein E alleles and genotypes were determined, and their distributions were compared on the basis of glaucoma status. Similar analyses were performed using positive control outcomes associated with the APOE E4 allele (death, dementia, age-related macular degeneration) and negative control outcomes not associated with the APOE E4 allele (cataract, diabetic eye disease). Outcome phenotypes were also correlated with Alzheimer's dementia (AD), a clinical outcome highly associated with the APOE E4 allele.<br><br>MAIN OUTCOME MEASURES: Results of APOE E4 genotype-phenotype comparisons were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Replication analyses investigated APOE E4 associations in 2 replication cohorts (CLSA and ANZRAG/BMES).<br><br>RESULTS: The APOE E4 allele was inversely associated with glaucoma (OR, 0.96; 95% CI, 0.93-0.99; P&#xa0;= 0.016) and both negative controls (cataract: OR, 0.98; 95% CI, 0.96-0.99; P&#xa0;= 0.015; diabetic eye disease: OR, 0.92; 95% CI, 0.87-0.97; P&#xa0;= 0.003) in the UKBB cohort. A paradoxical positive association was observed between AD and both glaucoma (OR, 1.30; 95% CI, 1.08-1.54; P < 0.01) and cataract (OR, 1.15; 1.04-1.28; P&#xa0;= 0.018). No association between the APOE E4 allele and glaucoma was observed in either replication cohort (CLSA: OR, 1.03; 95% CI, 0.89-1.19; P&#xa0;= 0.66; ANZRAG/BMES: OR, 0.97; 95% CI, 0.84-1.12; P&#xa0;= 0.65).<br><br>CONCLUSIONS: A small negative association observed between APOE E4 and glaucoma within the UKBB was not evident in either replication cohort and may represent an artifact of glaucoma underdiagnosis in APOE E4 carriers.<br><br>FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid37006905,
year = {2022},
author = {Ericksen, CJ and Christensen, CA and Berger, B and Gune, S and Nielsen, JS},
title = {Implantation Site of a Port Delivery System With Ranibizumab: Anterior Segment Optical Coherence Tomography Evaluation.},
journal = {Journal of vitreoretinal diseases},
volume = {6},
number = {5},
pages = {347-350},
pmid = {37006905},
issn = {2474-1272},
abstract = {Purpose: To determine whether anterior segment optical coherence tomography (AS-OCT) can be used to obtain noninvasive high-resolution images for monitoring the implantation site of a port delivery system with ranibizumab (PDS). Methods: Six eyes from the Archway phase 3 trial were imaged with AS-OCT after surgical implantation of the PDS and at regular follow-up visits. Results: AS-OCT was helpful in monitoring the status of the overlying conjunctiva and Tenon capsule after implantation of the PDS. Minimal qualitative thinning was observed over the implants at the longest follow-up. No cases of conjunctival erosion were noted. Conclusions: AS-OCT can be used to help to monitor PDS implants and potential associated complications.},
}
@article {pmid37006663,
year = {2023},
author = {Nielsen, JS and Roberts, CL and Saggau, DD and Alliman, KJ},
title = {High-Dose Aflibercept for Neovascular AMD and DME in Suboptimal Responders to Standard-Dose Aflibercept.},
journal = {Journal of vitreoretinal diseases},
volume = {7},
number = {2},
pages = {116-124},
pmid = {37006663},
issn = {2474-1272},
abstract = {Purpose: To assess the effect of higher dose (HD) aflibercept on visual acuity (VA), optical coherence tomography outcomes, and injection burden in eyes with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) that responded suboptimally to standard-dose aflibercept. Methods: This retrospective analysis included eyes with clinically significant disease activity on monthly therapy (AMT) (injection interval ≤35 days) or clinically significant increased activity on extension (IAE) (injection interval >36 days) that were switched from aflibercept 2 mg to aflibercept HD (3 mg to 4 mg). Outcomes were assessed at baseline, after injections 1 through 4, and at 6, 9, and 12 months. Results: Overall, 318 eyes of 288 adult patients were analyzed (eyes with nAMD: 59 AMT, 147 IAE; eyes with DME: 50 AMT, 62 IAE). Most of the study cohort received aflibercept HD 3 mg (nAMD: 73% AMT and 58% IAE; DME: 49% AMT and 68% IAE); the remainder received 4 mg. The mean best VA improved significantly with AMT and was maintained with IAE. In all groups, the central subfield thickness decreased significantly and the mean injection intervals increased or remained stable. No new safety signals were observed. Conclusions: Aflibercept HD might improve outcomes while decreasing treatment burden for eyes that respond suboptimally to standard dosing.},
}
@article {pmid37004107,
year = {2023},
author = {Jiang, D and Yan, C and Ge, L and Yang, C and Huang, Y and Chan, YK and Chen, C and Chen, W and Zhou, M and Lin, B},
title = {Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema.},
journal = {Eye and vision (London, England)},
volume = {10},
number = {1},
pages = {14},
pmid = {37004107},
issn = {2326-0254},
support = {82000909//Young Scientists Fund/ ; },
abstract = {BACKGROUND: Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME.<br><br>METHODS: Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways.<br><br>RESULTS: The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME.<br><br>CONCLUSIONS: Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.},
}
@article {pmid37003480,
year = {2023},
author = {Trivizki, O and Wang, L and Shi, Y and Rabinovitch, D and Iyer, P and Gregori, G and Feuer, W and Rosenfeld, PJ},
title = {Symmetry of Macular Fundus Features in Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {8},
pages = {672-682},
pmid = {37003480},
issn = {2468-6530},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Female ; Aged ; Male ; *Retinal Drusen/diagnosis ; Prospective Studies ; *Macular Degeneration/diagnosis ; Retina ; *Geographic Atrophy/diagnosis ; },
abstract = {PURPOSE: The symmetry of major macular fundus features in both eyes of the same patient with age-related macular degeneration (AMD) was investigated using swept-source(SS)-OCT.<br><br>DESIGN: Retrospective review of a prospective study.<br><br>PARTICIPANTS: Patients with AMD.<br><br>METHODS: Grading was performed on the first SS-OCT images obtained on the patients. Two graders diagnosed the presence of drusen, geographic atrophy (GA), and exudative AMD (eAMD) in each eye. Medical records were reviewed to assess prior exudation. To assess symmetry, 1 eye of each patient was randomly selected as the index eye and compared with the fellow eye. The kappa statistic (&#x3ba;) was used to assess the symmetry of diagnosis. The intraclass correlation coefficient (ICC) was used to assess the symmetry of drusen area and volume.<br><br>MAIN OUTCOME MEASURES: Interocular symmetry of the AMD stages: drusen, GA, and eAMD.<br><br>RESULTS: A total of 1310 patients with AMD were included. The average age was 78 years (range, 50-102; 60% women). Of the 1310 subjects, 54% (701) presented with symmetric disease: 20% with bilateral drusen, 11% with bilateral GA, and 22% with bilateral eAMD. Only 0.5% of the subjects had both GA and eAMD in both eyes. Of the randomly selected index eyes, 825 (47%) were right eyes. Overall, limited interocular agreement was observed between the index and fellow eyes (54%; &#x3ba;&#xa0;= 0.29). Kappa coefficients were poor (< 0.4) for index eyes diagnosed with drusen (&#x3ba;&#xa0;= 0.27), eAMD (&#x3ba;&#xa0;= 0.17), and mixed disease (&#x3ba;&#xa0;= 0.03). There was moderate agreement between the index and fellow eyes for GA (&#x3ba;&#xa0;= 0.50). Of the 265 patients with bilateral drusen, the symmetry of drusen area measurements had moderate ICC values of 0.70, 0.71, and 0.70 in the 3- and 5-mm diameter foveal-centered circles and in the total scan area, respectively. The ICC values for the drusen volumes were 0.65, 0.66, and 0.64, respectively.<br><br>CONCLUSIONS: Interocular symmetry was poor for eyes with drusen, eAMD, and mixed disease, but moderate for GA. Although the diagnosis of drusen was not very symmetric between eyes, when present in both eyes, the drusen area and volume measurements were moderately symmetric.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid37001591,
year = {2023},
author = {Ha, A and Kim, SH and Kang, G and Yoon, HJ and Kim, YK},
title = {Association between Sight-Threatening Eye Diseases and Death by Suicide in South Korea: A Nationwide Population-based Cohort Study.},
journal = {Ophthalmology},
volume = {130},
number = {8},
pages = {804-811},
doi = {10.1016/j.ophtha.2023.03.018},
pmid = {37001591},
issn = {1549-4713},
mesh = {Humans ; Male ; Female ; Cohort Studies ; Vision Disorders/epidemiology ; *Suicide/psychology ; *Vision, Low ; Republic of Korea/epidemiology ; *Glaucoma/epidemiology ; Risk Factors ; },
abstract = {PURPOSE: Although associations between visual impairment (VI) and suicide are posited, specific risks across the sight-threatening eye disease (STED) spectrum remain to be assessed. We determined whether individuals with STED die more often by suicide than do other people and assessed the temporal associations.<br><br>DESIGN: A nationwide, population-based cohort study.<br><br>PARTICIPANTS: All persons aged 40 years or older in South Korea from 2010 to&#xa0;2020.<br><br>METHODS: Persons diagnosed with STEDs (i.e., glaucoma, exudative age-related macular degeneration [AMD], or diabetic retinopathy [DR]) were identified in the Korean National Health Insurance (NHI) service database. Both NHI health checkup records and the National Disability Registration were used for coexisting severe VI. Death by suicide was defined as diagnostic codes as recorded in the Korea National Statistical Office. Incidence rate ratios (IRRs) were estimated by quasi-Poisson regressions and adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and VI. The temporal relationship between time since first STED diagnosis and suicide risk was determined by identifying patients with STED newly diagnosed during the period from 2010 to&#xa0;2011.<br><br>MAIN OUTCOME MEASURES: The IRR of death by suicide in people with STED relative to those without.<br><br>RESULTS: Of the 2.8 million people (45% male) observed for 24 300 969 person-years, 13 205 died by suicide. Among them, 34% (n&#xa0;= 4514) had a STED diagnosis, for a suicide rate of 69 per 100 000 person-years (95% confidence interval [CI], 67-72), relative to 51 per 100 000 person-years (95% CI, 50-52) for non-STED individuals. People with STED had an adjusted IRR of 1.33 (95% CI, 1.26-1.41) relative to those without. The largest excess adjusted IRR of suicide mortality was that for DR (1.40, 95% CI, 1.29-1.52). For exudative AMD, the adjusted IRR was 1.20 (95% CI, 1.04-1.39), whereas for glaucoma, the corresponding value was 1.09 (95% CI, 1.02-1.17). With coexisting severe VI, the IRR for any STED was 1.49 (95% CI, 1.29-1.73). The highest suicide hazard ratio was between 3 and 6 months postdiagnosis (5.33; 95% CI, 4.59-6.20).<br><br>CONCLUSIONS: In South Korea between 2010 and 2020, a higher suicide rate was evident among those with diagnosed STED than for persons not so diagnosed.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid37000271,
year = {2023},
author = {Terao, R and Obata, R and Okubo, A and Aoki, S and Azuma, K and Ahmed, T and Inoda, S and Hashimoto, Y and Takahashi, R and Yoshida, H and Misawa, M and Takahashi, H and Takahashi, H},
title = {Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {9},
pages = {2465-2476},
pmid = {37000271},
issn = {1435-702X},
mesh = {Humans ; *Granulocyte-Macrophage Colony-Stimulating Factor/metabolism/therapeutic use ; Aqueous Humor/metabolism ; Interleukin-10 ; E-Selectin/metabolism/therapeutic use ; Interleukin-8/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Ligands ; Cytokines/metabolism ; Interleukin-6 ; Granulocyte Colony-Stimulating Factor/metabolism/therapeutic use ; *Macular Degeneration/drug therapy ; Inflammation/metabolism ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {PURPOSE: To identify the inflammatory cytokine profile in the aqueous humor (AH) of patients with intraocular inflammation (IOI) after intravitreal administration of brolucizumab (IVBr) for neovascular age-related macular degeneration.<br><br>METHODS: Eight eyes from seven patients with IOI after initial IVBr (IVBrIOI&#x2009;+) were enrolled. Sixteen eyes from 16 patients without IOI after IVBr (IVBrIOI&#x2009;-) and aflibercept (IVA) were used as controls. AH samples were analyzed using a multiplex immunoassay.<br><br>RESULTS: C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)1, CXCL10, CXCL13, interleukin (IL)-6, IL-8, IL-10, matrix metalloproteinase (MMP)-1, MMP-9, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule (ICAM)-1, E-selectin, and P-selectin levels were significantly higher in IVBrIOI&#x2009;+&#x2009;than in IVBrIOI&#x2009;-&#x2009;and IVA. Vascular endothelial growth factor (VEGF) was significantly lower in IVBrIOI&#x2009;-&#x2009;compared to that in IVBrIOI&#x2009;+&#x2009;and IVA. In the IVBrIOI&#x2009;+&#x2009;group, there were significant correlations between CCL2, CXCL1, IL-6, IL-8, IL-10, G-CSF, GM-CSF, ICAM-1, and E-selectin, which also exhibited significant correlations in the IVBrIOI&#x2009;-&#x2009;group.<br><br>CONCLUSION: The number of inflammatory cytokines increases during IOI, which is associated with type IV hypersensitivity and vascular inflammation. Some cytokines exhibit correlations even in non-inflamed eyes, indicating a subclinical response to IVBr.},
}
@article {pmid36997794,
year = {2023},
author = {Singh, SR and Goté, JT and Chhablani, J},
title = {Randomized controlled trials in central serous chorioretinopathy: A review.},
journal = {Eye (London, England)},
volume = {37},
number = {16},
pages = {3306-3312},
pmid = {36997794},
issn = {1476-5454},
mesh = {Humans ; *Central Serous Chorioretinopathy/diagnosis/surgery ; Visual Acuity ; Randomized Controlled Trials as Topic ; Eplerenone/therapeutic use ; Spironolactone ; Tomography, Optical Coherence/methods ; },
abstract = {Central serous chorioretinopathy (CSCR), a common chorioretinal disease, presents with a myriad of manifestations. Acute CSCR presents with localized neurosensory detachment whereas chronic CSCR may show widespread retinal pigment epithelium (RPE) changes, chronic shallow subretinal fluid, and choroidal neovascularization (CNV) suggestive of a variable natural history leading to suboptimal visual outcomes. Even though multiple treatment options including laser photocoagulation, photodynamic therapy, micropulse laser, anti-vascular endothelial growth factors, and systemic drugs (spironolactone, eplerenone, melatonin, mifepristone) are available, there is an absence of any standardized treatment protocol or gold standard treatment modality. Moreover, their performance compared to observation especially in acute CSCR is still debatable. Compared to other chorioretinal diseases such as age-related macular degeneration, diabetic retinopathy, diabetic macular oedema, and retinal vein occlusion, there is a relative dearth of randomized controlled trials in CSCR. Multiple inconsistencies including reliance on history of disease duration, variable inclusion criteria/disease descriptors/study endpoints, and availability of multiple treatment modalities lead to difficulties in designing RCTs. A consensus-based treatment protocol, therefore, is still elusive. We reviewed the literature and compiled the list of papers published to date, wherein we analyse and compare the inclusion criteria, imaging modalities, study endpoints, study duration, and study results. Correcting these discrepancies and deficiencies will help standardize future study designs, facilitating a next step toward a standardized treatment protocol.},
}
@article {pmid36996856,
year = {2023},
author = {Guymer, RH and Campbell, TG},
title = {Age-related macular degeneration.},
journal = {Lancet (London, England)},
volume = {401},
number = {10386},
pages = {1459-1472},
doi = {10.1016/S0140-6736(22)02609-5},
pmid = {36996856},
issn = {1474-547X},
mesh = {Humans ; Middle Aged ; *Macular Degeneration/diagnosis/therapy ; Aging ; Visual Acuity ; },
abstract = {Age-related macular degeneration is an increasingly important public health issue due to ageing populations and increased longevity. Age-related macular degeneration affects individuals older than 55 years and threatens high-acuity central vision required for important tasks such as reading, driving, and recognising faces. Advances in retinal imaging have identified biomarkers of progression to late age-related macular degeneration. New treatments for neovascular age-related macular degeneration offer potentially longer-lasting effects, and progress is being made towards a treatment for atrophic late age-related macular degeneration. An effective intervention to slow progression in the earlier stages of disease, or to prevent late age-related macular degeneration development remains elusive, and our understanding of underlying mechanistic pathways continues to evolve.},
}
@article {pmid36996461,
year = {2023},
author = {Kalaw, FGP and Ignacio, JCI and Wu, CY and Ferreyra, H and Nudleman, E and Baxter, SL and Freeman, WR and Borooah, S},
title = {PENTOSAN POLYSULFATE SODIUM (ELMIRON) MACULOPATHY: A Genetic Perspective.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {7},
pages = {1174-1181},
pmid = {36996461},
issn = {1539-2864},
mesh = {Female ; Male ; Humans ; Pentosan Sulfuric Polyester/adverse effects ; *Cystitis, Interstitial ; *Macular Degeneration/chemically induced/diagnosis/genetics ; *Retinal Dystrophies ; *Cone-Rod Dystrophies ; },
abstract = {PURPOSE: To assess genetic associations for pentosan polysufate sodium maculopathy.<br><br>METHODS: Genetic testing for inherited retinal dystrophy genes using exome testing and for 14 age-related macular degeneration-associated single nucleotide polymorphisms (SNPs) using panel testing were performed. In addition, full-field electroretinograms (ffERG) were obtained to identify any cone-rod dystrophy.<br><br>RESULTS: Eleven of 15 patients were women, with a mean age of 69 (range 46-85). Inherited retinal dystrophy exome testing in five patients revealed six pathogenic variants, but failed to confirm inherited retinal dystrophy in any patient genetically. FfERG performed in 12 patients demonstrated only nonspecific a- and b-wave abnormalities in 11 cases and was normal in one case. For age-related macular degeneration single nucleotide polymorphisms, CFH rs3766405 (P = 0.003) and CETP (P = 0.027) were found to be statistically significantly associated with pentosan polysulfate maculopathy phenotype compared with the control population.<br><br>CONCLUSION: Pentosan polysulfate maculopathy is not associated with Mendelian inherited retinal dystrophy genes. However, several age-related macular degeneration risk alleles were identified to be associated with maculopathy compared with their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate.},
}
@article {pmid36996458,
year = {2023},
author = {Fouad, YA and Santina, A and Bousquet, E and Sadda, SR and Sarraf, D},
title = {Pathways of Fluid Leakage in Age-Related Macular Degeneration.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {6},
pages = {873-881},
doi = {10.1097/IAE.0000000000003798},
pmid = {36996458},
issn = {1539-2864},
mesh = {Humans ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Tomography, Optical Coherence ; Fluorescein Angiography ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
}
@article {pmid36993501,
year = {2023},
author = {Dhingra, A and Tobias, JW and Philp, NJ and Boesze-Battaglia, K},
title = {Transcriptomic changes predict metabolic alterations in LC3 associated phagocytosis in aged mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.03.14.532586},
pmid = {36993501},
issn = {2692-8205},
abstract = {LC3b (Map1lc3b) plays an essential role in canonical autophagy and is one of several components of the autophagy machinery that mediates non-canonical autophagic functions. Phagosomes are often associated with lipidated LC3b, to pro-mote phagosome maturation in a process called LC3-associated phagocytosis (LAP). Specialized phagocytes such as mammary epithelial cells, retinal pigment epithelial (RPE) cells, and sertoli cells utilize LAP for optimal degradation of phagocytosed material, including debris. In the visual system, LAP is critical to maintain retinal function, lipid homeostasis and neuroprotection. In a mouse model of retinal lipid steatosis - mice lacking LC3b (LC3b [-/-]), we observed increased lipid deposition, metabolic dysregulation and enhanced inflammation. Herein we present a non-biased approach to determine if loss of LAP mediated processes modulate the expression of various genes related to metabolic homeostasis, lipid handling, and inflammation. A comparison of the RPE transcriptome of WT and LC3b [-/-] mice revealed 1533 DEGs, with ~73% upregulated and 27% down-regulated. Enriched gene ontology (GO) terms included inflammatory response (upregulated DEGs), fatty acid metabolism and vascular transport (downregulated DEGs). Gene set enrichment analysis (GSEA) identified 34 pathways; 28 were upregulated (dominated by inflammation/related pathways) and 6 were downregulated (dominated by metabolic pathways). Analysis of additional gene families identified significant differences for genes in the solute carrier family, RPE signature genes, and genes with potential role in age-related macular degeneration. These data indicate that loss of LC3b induces robust changes in the RPE transcriptome contributing to lipid dysregulation and metabolic imbalance, RPE atrophy, inflammation, and disease pathophysiology.},
}
@article {pmid36990322,
year = {2023},
author = {MacCumber, MW and Wykoff, CC and Karcher, H and Adiguzel, E and Sinha, SB and Vishwakarma, S and LaPrise, A and Igwe, F and Freitas, R and Ip, MS and Zarbin, MA},
title = {Factors Linked to Injection Interval Extension in Eyes with Wet Age-Related Macular Degeneration Switched to Brolucizumab.},
journal = {Ophthalmology},
volume = {130},
number = {8},
pages = {795-803},
doi = {10.1016/j.ophtha.2023.03.017},
pmid = {36990322},
issn = {1549-4713},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; Recombinant Fusion Proteins/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; },
abstract = {PURPOSE: To evaluate factors associated with anti-vascular endothelial growth factor (VEGF) injection interval extension in patients with neovascular age-related macular degeneration (nAMD) switched to brolucizumab treatment.<br><br>DESIGN: Retrospective, observational cohort study.<br><br>PARTICIPANTS: Adults in the United States-based IRIS&#xae; Registry (Intelligent Research in Sight) with nAMD who switched from another anti-VEGF agent to brolucizumab-only treatment for &#x2265; 12 months from October 8, 2019, through November 26,&#xa0;2021.<br><br>METHODS: Univariable and multivariable analyses examined associations of demographic and clinical characteristics with the likelihood of interval extension after switching to brolucizumab therapy.<br><br>MAIN OUTCOME MEASURES: Eyes were classified as either extenders or nonextenders at 12 months. Extenders were eyes that achieved (1) an extension of &#x2265; 2 weeks in the brolucizumab injection interval at 12 months versus the interval before switching (time between the last known prior anti-VEGF injection and first [index] brolucizumab injection) and (2) stable (< 10 letters gained or lost) or improved (&#x2265; 10 letters gained) visual acuity (VA) at 12 months versus VA at index injection.<br><br>RESULTS: Of 2015 eyes among 1890 patients who switched to brolucizumab treatment, 1186 (58.9%) were extenders. In univariable analyses, demographic and clinical characteristics were comparable between extenders and nonextenders, except that extenders had shorter intervals before switching versus nonextenders (mean, 5.9 &#xb1; 2.1 weeks vs. 10.1 &#xb1; 7.6 weeks, respectively). In multivariable logistic regression modeling, a shorter interval before switching was associated significantly and positively with interval extension with brolucizumab therapy (adjusted odds ratio, 5.6 for interval before switching of < 8 weeks versus &#x2265; 8 weeks; 95% confidence interval, 4.5-6.9; P < 0.001), and eyes with an index VA of 40 to 65 letters were significantly less likely to be extenders than eyes in the higher (better) index VA categories.<br><br>CONCLUSIONS: Length of the treatment interval before switching was the characteristic associated most strongly with successful interval extension with brolucizumab. Treatment-experienced patients who required more frequent injections (i.e., shorter intervals before switching) showed the greatest extensions when switching to brolucizumab. With careful consideration of benefits and risks, brolucizumab may be a valuable option for patients with higher treatment burdens because of the need for frequent injections.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36990246,
year = {2023},
author = {Song, D and Lee, JY and Park, EC and Choi, NE and Nam, HY and Seo, J and Lee, J},
title = {Structure-activity relationship analysis of activity-based probes targeting HTRA family of serine proteases.},
journal = {Bioorganic &amp; medicinal chemistry letters},
volume = {87},
number = {},
pages = {129259},
doi = {10.1016/j.bmcl.2023.129259},
pmid = {36990246},
issn = {1464-3405},
mesh = {*Serine Proteases/metabolism ; *Serine Endopeptidases/metabolism ; Structure-Activity Relationship ; },
abstract = {High temperature requirement A serine proteases (HTRA) are ubiquitously expressed and participate in protein quality control and cellular stress responses. They are linked to several clinical illnesses, including bacterial infection, cancer, age-related macular degeneration, and neurodegenerative diseases. In addition, several recent studies have revealed HTRAs as important biomarkers and potential therapeutic targets, necessitating the development of an effective detection method to evaluate their functional states in various disease models. We developed a new series of HTRA-targeting activity-based probes with enhanced subtype selectivity and reactivity. In conjunction with our previously developed tetrapeptide probes, we established the structure-activity relationship of the new probes for different HTRA subtypes. Our probes are cell-permeable and have potent inhibitory effects against HTRA1 and HTRA2, making them valuable for identifying and validating HTRAs as an important biomarker.},
}
@article {pmid36986699,
year = {2023},
author = {Patel, C and Pande, S and Sagathia, V and Ranch, K and Beladiya, J and Boddu, SHS and Jacob, S and Al-Tabakha, MM and Hassan, N and Shahwan, M},
title = {Nanocarriers for the Delivery of Neuroprotective Agents in the Treatment of Ocular Neurodegenerative Diseases.},
journal = {Pharmaceutics},
volume = {15},
number = {3},
pages = {},
pmid = {36986699},
issn = {1999-4923},
abstract = {Retinal neurodegeneration is considered an early event in the pathogenesis of several ocular diseases, such as diabetic retinopathy, age-related macular degeneration, and glaucoma. At present, there is no definitive treatment to prevent the progression or reversal of vision loss caused by photoreceptor degeneration and the death of retinal ganglion cells. Neuroprotective approaches are being developed to increase the life expectancy of neurons by maintaining their shape/function and thus prevent the loss of vision and blindness. A successful neuroprotective approach could prolong patients' vision functioning and quality of life. Conventional pharmaceutical technologies have been investigated for delivering ocular medications; however, the distinctive structural characteristics of the eye and the physiological ocular barriers restrict the efficient delivery of drugs. Recent developments in bio-adhesive in situ gelling systems and nanotechnology-based targeted/sustained drug delivery systems are receiving a lot of attention. This review summarizes the putative mechanism, pharmacokinetics, and mode of administration of neuroprotective drugs used to treat ocular disorders. Additionally, this review focuses on cutting-edge nanocarriers that demonstrated promising results in treating ocular neurodegenerative diseases.},
}
@article {pmid36984552,
year = {2023},
author = {Yahalomi, T and Pikkel, Y and Arnon, R and Porat, D and Pikkel, J},
title = {The HIT Study-The Hydroxychloroquine Effect in the Treatment of Patients with Age-Related Macular Degeneration: A Randomized Controlled Trial.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {3},
pages = {},
pmid = {36984552},
issn = {1648-9144},
mesh = {Female ; Humans ; Hydroxychloroquine/adverse effects ; *Retinal Drusen ; Retina ; *Wet Macular Degeneration ; Tomography, Optical Coherence ; },
abstract = {Background and Objectives: Decreased age-related macular degeneration (AMD) has been reported in individuals with rheumatoid arthritis treated with hydroxychloroquine (HCQ, plaquenil). Materials and Methods: In a randomized controlled trial with a parallel study design, we assessed visual acuity, central macular thickness measured with macular optical coherence tomography (OCT), and the number and size of drusen, following treatment with HCQ or a placebo in individuals with AMD. The patients received a daily dosage of 400 mg hydroxychloroquine (study group) or placebo (control group) during 12 months, and underwent complete ophthalmic examinations at 3, 6, 9, 12 and 24 months after initiation of treatment. Results: Of the 110 patients who were randomized to the treatment groups, 46 (29 females) in the study group and 50 (29 females) in the control group completed the study. The study group showed less visual acuity deterioration at two-year follow-up than did the control group (-0.03 ± 0.07 vs. -0.07 ± 0.07, p = 0.027). At two years after treatment initiation, the mean number of drusen per eye was lower for ARDS2 (8.1 vs. 12.3, p = 0.045) in the study group, compared to the control group. Compared to the control group, the proportion of eyes with increased drusen growth was smaller for both ARDS2 and ARDS3 drusen in the study group, and the proportion of the total drusen with growth was smaller for the study group as well: 32/46 eyes (70%) vs. 40/50 eyes (80%). Drusen volume growth, as calculated by the area and height measured with macular OCT, was also more reduced in the study than the control group (0.20 ± 0.15 vs. 0.23 ± 0.16 mm[4], p = 0.05). None of the participants showed HCQ toxicity or adverse effects. Conclusion: Among patients with AMD, visual deterioration, the growth and the amount of drusen formation at two years after treatment initiation was less among those treated with HCQ than with a placebo. In this study, there was a negative association between HCQ treatment and wet AMD development.},
}
@article {pmid36984491,
year = {2023},
author = {Tsiropoulos, GN and Vallée, R and Calci, C and Gallo Castro, D and Ambresin, A},
title = {Patient Perspective on the Monitoring of Their Wet Age-Related Macular Degeneration during Coronavirus Disease 2019: A Retrospective Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {3},
pages = {},
pmid = {36984491},
issn = {1648-9144},
mesh = {Humans ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; *COVID-19 ; Communicable Disease Control ; *Wet Macular Degeneration ; },
abstract = {Background and Objectives: The purpose was to provide the patients' perspective on the monitoring of their wet age-related macular degeneration (wet AMD) during coronavirus disease 2019 (COVID-19) and the importance of telemedicine. Materials and Methods: Wet AMD patients that underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in two Swiss ophthalmology clinics, completed two questionnaires after the first confinement due to COVID-19 in Switzerland. The first evaluated their views concerning their adherence to scheduled injections during the confinement, and the application of telemedicine in the future. The second, adapted from the National Eye Institute Visual Function Questionnaire-25, assessed their opinions on visual function change during confinement. Results: From a total of 130 patients, 8.5% responded they did not respect their assigned schedule (group 1) while 91.5% responded they did (group 2). A total of 78.7% of group 2 considered treatment reception as more relevant compared to the risk of COVID-19 contraction. During the pre-lockdown period, group 2 patients required more help from others than group 1 patients (p = 0.02). In the possibility of another lockdown, 36.3% of group 1 and 8.7% of group 2 would choose telemedicine to monitor their wet AMD (p = 0.02), 54.5% and 86.9% would rather visit the clinic (p = 0.02), while 9.0% and 4.3% would cancel their appointment, respectively. It was found that 70% of group 1 and 33.6% of group 2 would prefer to use the telemedicine services than visiting a telemedicine centre (p = 0.04). Conclusions: During circumstances similar to the COVID-19 confinement, most patients would prefer to visit the clinic. Group 1 would prefer wet AMD monitoring via telemedicine at a higher rate than group 2.},
}
@article {pmid36983992,
year = {2023},
author = {Goodman, D and Ness, S},
title = {The Role of Oxidative Stress in the Aging Eye.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
pmid = {36983992},
issn = {2075-1729},
abstract = {Given the expanding elderly population in the United States and the world, it is important to understand the processes underlying both natural and pathological age-related changes in the eye. Both the anterior and posterior segment of the eye undergo changes in biological, chemical, and physical properties driven by oxidative stress. With advancing age, changes in the anterior segment include dermatochalasis, blepharoptosis, thickening of the sclera, loss of corneal endothelial cells, and stiffening of the lens. Changes in the posterior segment include lowered viscoelasticity of the vitreous body, photoreceptor cell loss, and drusen deposition at the macula and fovea. Age-related ocular pathologies including glaucoma, cataracts, and age-related macular degeneration are largely mediated by oxidative stress. The prevalence of these diseases is expected to increase in the coming years, highlighting the need to develop new therapies that address oxidative stress and slow the progression of age-related pathologies.},
}
@article {pmid36983970,
year = {2023},
author = {Hänsli, C and Schild, C and Pfister, I and Garweg, JG},
title = {Brolucizumab in Pretreated Neovascular Age-Related Macular Degeneration: Case Series, Systematic Review, and Meta-Analysis.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
pmid = {36983970},
issn = {2075-1729},
abstract = {BACKGROUND: Recalcitrant neovascular age-related macular degeneration (rnAMD) despite intensive intravitreal anti-neovascular endothelial growth factor (VEGF) treatment, can be handled by switching to another anti-VEGF agent. This first systematic review and meta-analysis presents long-term data after switching from another anti-VEGF agent to brolucizumab.<br><br>METHODS: Retrospective case series over two years of patients switched to brolucizumab, and a systematic review and meta-analysis of peer-reviewed studies presenting patients switched to brolucizumab. Weighted mean differences based on the random-effects models were calculated for best-corrected visual acuity (BCVA) and central subfield thickness (CST).<br><br>RESULTS: The systematic review draws on 1200 eyes switched to brolucizumab. The meta-analysis showed a clinically irrelevant decrease in BCVA after one and two months, together with significant decreases in CST for up to one year after the switch but lacking power over 2 years. Of twelve eyes (twelve patients) in our case series, five continued treatment for two years without experiencing significant changes.<br><br>CONCLUSIONS: After switch to brolucizumab, a significant morphological improvement with CST reduction was shown in eyes with rnAMD. The small worsening of BCVA may be owing to the chronically active nature of rnAMD. Brolucizumab thus remains a treatment option in rnAMD despite its potential side effects.},
}
@article {pmid36983878,
year = {2023},
author = {Gulias-Cañizo, R and Rodríguez-Malagón, ME and Botello-González, L and Belden-Reyes, V and Amparo, F and Garza-Leon, M},
title = {Applications of Infrared Thermography in Ophthalmology.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
pmid = {36983878},
issn = {2075-1729},
support = {NA//BCB Engineering/ ; },
abstract = {Body temperature is one of the key vital signs for determining a disease's severity, as it reflects the thermal energy generated by an individual's metabolism. Since the first study on the relationship between body temperature and diseases by Carl Reinhold August Wunderlich at the end of the 19th century, various forms of thermometers have been developed to measure body temperature. Traditionally, methods for measuring temperature can be invasive, semi-invasive, and non-invasive. In recent years, great technological advances have reduced the cost of thermographic cameras, which allowed extending their use. Thermal cameras capture the infrared radiation of the electromagnetic spectrum and process the images to represent the temperature of the object under study through a range of colors, where each color and its hue indicate a previously established temperature. Currently, cameras have a sensitivity that allows them to detect changes in temperature as small as 0.01 °C. Along with its use in other areas of medicine, thermography has been used at the ocular level for more than 50 years. In healthy subjects, the literature reports that the average corneal temperature ranges from 32.9 to 36 °C. One of the possible sources of variability in normal values is age, and other possible sources of variation are gender and external temperature. In addition to the evaluation of healthy subjects, thermography has been used to evaluate its usefulness in various eye diseases, such as Graves' orbitopathy, and tear duct obstruction for orbital diseases. The ocular surface is the most studied area. Ocular surface temperature is influenced by multiple conditions, one of the most studied being dry eye; other diseases studied include allergic conjunctivitis and pterygium as well as systemic diseases such as carotid artery stenosis. Among the corneal diseases studied are keratoconus, infectious keratitis, corneal graft rejection, the use of scleral or soft contact lenses, and the response to refractive or cataract surgery. Other diseases where thermographic features have been reported are glaucoma, diabetic retinopathy, age-related macular degeneration, retinal vascular occlusions, intraocular tumors as well as scleritis, and other inflammatory eye diseases.},
}
@article {pmid36983394,
year = {2023},
author = {Sanabria, MR and Calles-Monar, PS and Alonso-Tarancón, AM and Coco-Martín, RM and Mayo-Iscar, A},
title = {Impact of COVID-19 Confinement on Quality of Life of Patients with Age-Related Macular Degeneration: A Two-Wave Panel Study.},
journal = {Journal of clinical medicine},
volume = {12},
number = {6},
pages = {},
pmid = {36983394},
issn = {2077-0383},
support = {GRS 2111/A/19//Gerencia Regional de Salud de Castilla-Le&#xf3;n/ ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Intravitreal injections of antiangiogenic agents (anti-VEGF) can stop vision loss in the neovascular form of the disease (nAMD). The aim of this study was to assess the general health-related quality of life (HRQoL) in a cohort of patients with nAMD treated with intravitreal anti-VEGF injections and to detesrmine to what extent their HRQoL was affected by COVID-19. This was an observational, analytical, and longitudinal study performed with a two-wave panel survey. Clinical outcomes, HRQoL, and tangible support were evaluated. In the final survey, changes in living conditions and medical visits due to the COVID-19 pandemic were also examined. Of the 102 patients initially interviewed in the before-COVID survey, 24 were lost after 30 months of follow-up. In the initial assessment, the mean health index was 0.73 ± 0.2. The EQ VAS score worsened at the final survey (p = 0.048). Patients needing treatment in both eyes (p = 0.007) and with lower levels of bilateral visual acuity (p = 0.018) reported an increase in social support at the final survey. In conclusion, patients perceived a worsening in HRQoL after confinement. However, patients enjoyed good social support that improved in the after-COVID survey.},
}
@article {pmid36983068,
year = {2023},
author = {Antemie, RG and Samoilă, OC and Clichici, SV},
title = {Blue Light-Ocular and Systemic Damaging Effects: A Narrative Review.},
journal = {International journal of molecular sciences},
volume = {24},
number = {6},
pages = {},
pmid = {36983068},
issn = {1422-0067},
mesh = {Humans ; *Light ; *Vision, Ocular ; Retina ; Retinal Ganglion Cells/physiology ; Visual Acuity ; },
abstract = {Light is a fundamental aspect of our lives, being involved in the regulation of numerous processes in our body. While blue light has always existed in nature, with the ever-growing number of electronic devices that make use of short wavelength (blue) light, the human retina has seen increased exposure to it. Because it is at the high-energy end of the visible spectrum, many authors have investigated the theoretical harmful effects that it poses to the human retina and, more recently, the human body, given the discovery and characterization of the intrinsically photosensitive retinal ganglion cells. Many approaches have been explored, with the focus shifting throughout the years from examining classic ophthalmological parameters, such as visual acuity, and contrast sensitivity to more complex ones seen on electrophysiological assays and optical coherence tomographies. The current study aims to gather the most recent relevant data, reveal encountered pitfalls, and suggest future directions for studies regarding local and/or systemic effects of blue light retinal exposures.},
}
@article {pmid36982372,
year = {2023},
author = {Fontaine, V and Balducci, C and Dinan, L and Monteiro, E and Boumedine, T and Fournié, M and Nguyen, V and Guibout, L and Clatot, J and Latil, M and Veillet, S and Sahel, JA and Lafont, R and Dilda, PJ and Camelo, S},
title = {Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD).},
journal = {International journal of molecular sciences},
volume = {24},
number = {6},
pages = {},
pmid = {36982372},
issn = {1422-0067},
mesh = {Animals ; Mice ; Anti-Inflammatory Agents/pharmacology/therapeutic use/metabolism ; ATP-Binding Cassette Transporters/metabolism ; Carotenoids/metabolism ; *Macular Degeneration/drug therapy/metabolism ; *Retinal Degeneration/drug therapy/metabolism ; Retinal Pigment Epithelium/metabolism ; Retinoids/pharmacology ; Rats ; },
abstract = {9'-cis-norbixin (norbixin/BIO201) protects RPE cells against phototoxicity induced by blue light and N-retinylidene-N-retinylethanolamine (A2E) in vitro and preserves visual functions in animal models of age-related macular degeneration (AMD) in vivo. The purpose of this study was to examine the mode of action and the in vitro and in vivo effects of BIO203, a novel norbixin amide conjugate. Compared to norbixin, BIO203 displays improved stability at all temperatures tested for up to 18 months. In vitro, BIO203 and norbixin share a similar mode of action involving the inhibition of PPARs, NF-κB, and AP-1 transactivations. The two compounds also reduce IL-6, IL-8, and VEGF expression induced by A2E. In vivo, ocular maximal concentration and BIO203 plasma exposure are increased compared to those of norbixin. Moreover, BIO203 administered systemically protects visual functions and retinal structure in albino rats subjected to blue-light illumination and in the retinal degeneration model of Abca4[-/-] Rdh8[-/-] double knock-out mice following 6 months of oral complementation. In conclusion, we report here that BIO203 and norbixin share similar modes of action and protective effects in vitro and in vivo. BIO203, with its improved pharmacokinetic and stability properties, could be developed for the treatment of retinal degenerative diseases such as AMD.},
}
@article {pmid36982157,
year = {2023},
author = {García-López, C and García-López, V and Matamoros, JA and Fernández-Albarral, JA and Salobrar-García, E and de Hoz, R and López-Cuenca, I and Sánchez-Puebla, L and Ramírez, JM and Ramírez, AI and Salazar, JJ},
title = {The Role of Citicoline and Coenzyme Q10 in Retinal Pathology.},
journal = {International journal of molecular sciences},
volume = {24},
number = {6},
pages = {},
pmid = {36982157},
issn = {1422-0067},
support = {Art&#xed;culo 83: 89-2022//UCM-VISUFARMA ESPA&#xd1;A/ ; },
mesh = {Humans ; Aged ; Cytidine Diphosphate Choline/pharmacology/therapeutic use ; Retina/pathology ; *Retinal Diseases/drug therapy/pathology ; *Neurodegenerative Diseases/pathology ; },
abstract = {Ocular neurodegenerative diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration are common retinal diseases responsible for most of the blindness causes in the working-age and elderly populations in developed countries. Many of the current treatments used in these pathologies fail to stop or slow the progression of the disease. Therefore, other types of treatments with neuroprotective characteristics may be necessary to allow a more satisfactory management of the disease. Citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular neurodegenerative pathologies. This review provides a compilation, mainly from the last 10 years, of the main studies that have been published on the use of these drugs in these neurodegenerative diseases of the retina, analyzing the usefulness of these drugs in these pathologies.},
}
@article {pmid36980486,
year = {2023},
author = {Kalra, G and Cetin, H and Whitney, J and Yordi, S and Cakir, Y and McConville, C and Whitmore, V and Bonnay, M and Reese, JL and Srivastava, SK and Ehlers, JP},
title = {Automated Identification and Segmentation of Ellipsoid Zone At-Risk Using Deep Learning on SD-OCT for Predicting Progression in Dry AMD.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {6},
pages = {},
pmid = {36980486},
issn = {2075-4418},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; K23-EY022947-01A1/EY/NEI NIH HHS/United States ; },
abstract = {BACKGROUND: The development and testing of a deep learning (DL)-based approach for detection and measurement of regions of Ellipsoid Zone (EZ) At-Risk to study progression in nonexudative age-related macular degeneration (AMD).<br><br>METHODS: Used in DL model training and testing were 341 subjects with nonexudative AMD with or without geographic atrophy (GA). An independent dataset of 120 subjects were used for testing model performance for prediction of GA progression. Accuracy, specificity, sensitivity, and intraclass correlation coefficient (ICC) for DL-based EZ At-Risk percentage area measurement was calculated. Random forest-based feature ranking of EZ At-Risk was compared to previously validated quantitative OCT-based biomarkers.<br><br>RESULTS: The model achieved a detection accuracy of 99% (sensitivity = 99%; specificity = 100%) for EZ At-Risk. Automatic EZ At-Risk measurement achieved an accuracy of 90% (sensitivity = 90%; specificity = 84%) and the ICC compared to ground truth was high (0.83). In the independent dataset, higher baseline mean EZ At-Risk correlated with higher progression to GA at year 5 (p < 0.001). EZ At-Risk was a top ranked feature in the random forest assessment for GA prediction.<br><br>CONCLUSIONS: This report describes a novel high performance DL-based model for the detection and measurement of EZ At-Risk. This biomarker showed promising results in predicting progression in nonexudative AMD patients.},
}
@article {pmid36979967,
year = {2023},
author = {Palmieri, F and Younis, S and Raslan, W and Fabozzi, L},
title = {Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration: Case Series.},
journal = {Biomedicines},
volume = {11},
number = {3},
pages = {},
pmid = {36979967},
issn = {2227-9059},
abstract = {PURPOSE: This study seeks to report the clinical and multimodal imaging findings of eight eyes of seven patients with neovascular age-related macular degeneration (nAMD) who developed bacillary layer detachment (BALAD). Setting/Venue: The patients were analysed at the Western Eye Hospital in London, UK.<br><br>METHODS: The approaches of this research include clinical examinations and multimodal imaging-based description of cases of nAMD with BALAD.<br><br>RESULTS: We report multimodal imaging findings of bacillary layer detachment (BALAD) in patients with nAMD.<br><br>CONCLUSIONS: A bacillary layer detachment was detected in patients with neovascular age-related macular degeneration. This multimodal imaging finding is not commonly described in the literature for this disease.},
}
@article {pmid36978871,
year = {2023},
author = {Panuthai, P and Phumsuay, R and Muangnoi, C and Maitreesophone, P and Kongkatitham, V and Mekboonsonglarp, W and Rojsitthisak, P and Likhitwitayawuid, K and Sritularak, B},
title = {Isolation and Identification of Dihydrophenanthrene Derivatives from Dendrobium virgineum with Protective Effects against Hydrogen-Peroxide-Induced Oxidative Stress of Human Retinal Pigment Epithelium ARPE-19 Cells.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {3},
pages = {},
pmid = {36978871},
issn = {2076-3921},
support = {CU_FRB65_hea (57)_066_33_10//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; },
abstract = {Oxidative stress is a significant factor in the development of age-related macular degeneration (AMD), which results from cell damage, dysfunction, and death in the retinal pigmented epithelium (RPE). The use of natural compounds with antioxidant properties to protect RPE cells from oxidative stress has been explored in Dendrobium, a genus of orchid plants belonging to the family Orchidaceae. Two new compounds and seven known compounds from the MeOH extract of the whole plant of Dendrobium virgineum were successfully isolated and structurally characterized. Out of all the compounds isolated, 2-methoxy-9,10-dihydrophenanthrene-4,5-diol (3) showed the highest protective effect against hydrogen peroxide (H2O2)-induced oxidative stress in human retinal pigment epithelial (ARPE-19) cells. Therefore, it was selected to evaluate its protective effect and mechanism on oxidative-stress-induced ARPE-19 cells. Cells were pre-treated with compound 3 at 25, 50, and 100 µg/mL for 24 h and then induced with 400 µM H2O2 for 1 h. The results demonstrated that compound 3 significantly (p < 0.05) increased cell viability by 10-35%, decreased ROS production by 10-30%, and reduced phosphorylation of p38, ERK1/2, and SAPK/JNK by 20-70% in a dose-dependent manner without toxicity. Furthermore, compound 3 significantly (p < 0.05) modulated the expression of apoptosis pathway proteins (cytochrome c, Bax and Bcl-2) by 20-80%, and enhanced SOD, CAT, and GPX activities, and GSH levels in a dose-dependent manner. These results suggest that compound 3 protects ARPE-19 cells against oxidative stress through MAPKs and apoptosis pathways, including the antioxidant system. Thus, compound 3 could be considered as an antioxidant agent for preventing AMD development by protecting RPE cells from oxidative stress and maintaining the retina. These findings open up new possibilities for the use of natural compounds in the treatment of AMD and other oxidative-stress-related conditions.},
}
@article {pmid36978865,
year = {2023},
author = {Longoni, B and Demontis, GC},
title = {Polyunsaturated Lipids in the Light-Exposed and Prooxidant Retinal Environment.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {3},
pages = {},
pmid = {36978865},
issn = {2076-3921},
abstract = {The retina is an oxidative stress-prone tissue due to high content of polyunsaturated lipids, exposure to visible light stimuli in the 400-480 nm range, and high oxygen availability provided by choroidal capillaries to support oxidative metabolism. Indeed, lipids' peroxidation and their conversion into reactive species promoting inflammation have been reported and connected to retinal degenerations. Here, we review recent evidence showing how retinal polyunsaturated lipids, in addition to oxidative stress and damage, may counteract the inflammatory response triggered by blue light-activated carotenoid derivatives, enabling long-term retina operation despite its prooxidant environment. These two aspects of retinal polyunsaturated lipids require tight control over their synthesis to avoid overcoming their protective actions by an increase in lipid peroxidation due to oxidative stress. We review emerging evidence on different transcriptional control mechanisms operating in retinal cells to modulate polyunsaturated lipid synthesis over the life span, from the immature to the ageing retina. Finally, we discuss the antioxidant role of food nutrients such as xanthophylls and carotenoids that have been shown to empower retinal cells' antioxidant responses and counteract the adverse impact of prooxidant stimuli on sight.},
}
@article {pmid36977729,
year = {2023},
author = {Lee, S and Kim, KT and Kim, DY and Chae, JB and Seo, EJ},
title = {Outer nuclear layer recovery as a predictor of visual prognosis in type 1 choroidal neovascularization of neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {5045},
pmid = {36977729},
issn = {2045-2322},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Prognosis ; *Choroidal Neovascularization/diagnostic imaging/drug therapy ; Vascular Endothelial Growth Factors ; Tomography, Optical Coherence ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; },
abstract = {To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.},
}
@article {pmid36977322,
year = {2023},
author = {Kim, JH and Kim, JW and Kim, CG},
title = {INCIDENCE AND TIMING OF PIGMENT EPITHELIAL DETACHMENT AND SUBRETINAL FLUID DEVELOPMENT IN TYPE 3 MACULAR NEOVASCULARIZATION ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {8},
pages = {1264-1273},
doi = {10.1097/IAE.0000000000003797},
pmid = {36977322},
issn = {1539-2864},
mesh = {Humans ; Angiogenesis Inhibitors ; Subretinal Fluid ; Retrospective Studies ; Incidence ; Intravitreal Injections ; Visual Acuity ; Ranibizumab ; *Macular Degeneration/diagnosis ; *Retinal Detachment/diagnosis ; Neovascularization, Pathologic/drug therapy ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To evaluate the incidence and timing of pigment epithelial detachment (PED) and subretinal fluid (SRF) development in type 3 macular neovascularization.<br><br>METHODS: This retrospective study included 84 patients who were diagnosed with treatment-na&#xef;ve type 3 macular neovascularization who did not show SRF at diagnosis. All patients were initially treated with three loading injections of ranibizumab or aflibercept. After the initial loading injections, as-needed regimen was performed for retreatment. The development of either PED or SRF was identified. The incidence and timing of PED development in patients without PED at diagnosis and that of SRF development in patients with PED at diagnosis were evaluated.<br><br>RESULTS: The mean follow-up period was 41.3 &#xb1; 20.7 months after diagnosis. Among the 32 patients without serous PED at diagnosis, PED developed in 20 (62.5%) at a mean of 10.9 &#xb1; 5.1 months after diagnosis. PED development was noted within 12 months in 15 patients (46.8%; 75.0% among the PED development cases). In 52 patients with serous PED and without SRF at diagnosis, 15 developed SRF (28.8%) at a mean of 11.2 &#xb1; 6.4 months after diagnosis. SRF development was noted within 12 months in nine patients (17.3%; 66.6% among the SRF development cases).<br><br>CONCLUSION: PED and SRF developed in a substantial proportion of patients with type 3 macular neovascularization. The average period of development of these pathologic findings was within 12 months of diagnosis, suggesting the need for active treatment during the early treatment period to improve treatment outcomes.},
}
@article {pmid36976187,
year = {2023},
author = {Yang, C and Yang, R and Gu, M and Hao, J and Wang, S and Li, C},
title = {Chitooligosaccharides Derivatives Protect ARPE-19 Cells against Acrolein-Induced Oxidative Injury.},
journal = {Marine drugs},
volume = {21},
number = {3},
pages = {},
pmid = {36976187},
issn = {1660-3397},
support = {U21A20297//National Natural Science Foundation of China/ ; 2021ZDSYS22//Shandong Major Science and Technology Project/ ; ZR2021QH144//Shandong Provincial Natural Science Foundation/ ; 2018ZX09735004//National Science and Technology Major Project for Significant New Drugs Development/ ; },
mesh = {Humans ; Aged ; *Antioxidants/pharmacology/metabolism ; Acrolein/toxicity ; Cell Survival ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; *Macular Degeneration/chemically induced/drug therapy/prevention &amp; control ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and N-acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS-5) and its N-acetylated derivative (N-5) showed the best protective activity. Pretreatment with COS-5 or N-5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N-5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.},
}
@article {pmid36973405,
year = {2023},
author = {Balaskas, K and Drawnel, F and Khanani, AM and Knox, PC and Mavromaras, G and Wang, YZ},
title = {Home vision monitoring in patients with maculopathy: current and future options for digital technologies.},
journal = {Eye (London, England)},
volume = {37},
number = {15},
pages = {3108-3120},
pmid = {36973405},
issn = {1476-5454},
mesh = {Humans ; Digital Technology ; *Macular Degeneration/diagnosis ; *Diabetic Retinopathy ; *Macular Edema/diagnosis ; Retina ; },
abstract = {Patients with macular pathology, including that caused by age-related macular degeneration and diabetic macular oedema, must attend frequent in-clinic monitoring appointments to detect onset of disease activity requiring treatment and to monitor progression of existing disease. In-person clinical monitoring places a significant burden on patients, caregivers and healthcare systems and is limited in that it only provides clinicians with a snapshot of the patient's disease status. The advent of remote monitoring technologies offers the potential for patients to test their own retinal health at home in collaboration with clinicians, reducing the need for in-clinic appointments. In this review we discuss visual function tests, both existing and novel, that have the potential for remote use and consider their suitability for discriminating the presence of disease and progression of disease. We then review the clinical evidence supporting the use of mobile applications for monitoring of visual function from clinical development through to validation studies and real-world implementation. This review identified seven app-based visual function tests: four that have already received some form of regulatory clearance and three under development. The evidence included in this review shows that remote monitoring offers great potential for patients with macular pathology to monitor their condition from home, reducing the need for burdensome clinic visits and expanding clinicians' understanding of patients' retinal health beyond traditional clinical monitoring. In order to instil confidence in the use of remote monitoring in both patients and clinicians further longitudinal real-world studies are now warranted.},
}
@article {pmid36973337,
year = {2023},
author = {Brown, HDH and Gale, RP and Gouws, AD and Vernon, RJW and Airody, A and Hanson, RLW and Baseler, HA and Morland, AB},
title = {Assessing the structure of the posterior visual pathway in bilateral macular degeneration.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {5008},
pmid = {36973337},
issn = {2045-2322},
support = {BB/P007252/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Humans ; Visual Pathways/diagnostic imaging ; Cross-Sectional Studies ; Magnetic Resonance Imaging ; Occipital Lobe ; *White Matter/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; },
abstract = {Macular degeneration (MD) embodies a collection of disorders causing a progressive loss of central vision. Cross-sectional MRI studies have revealed structural changes in the grey and white matter in the posterior visual pathway in MD but there remains a need to understand how such changes progress over time. To that end we assessed the posterior pathway, characterising the visual cortex and optic radiations over a ~ 2-year period in MD patients and controls. We performed cross-sectional and longitudinal analysis of the former. Reduced cortical thickness and white matter integrity were observed in patients compared to controls, replicating previous findings. While faster, neither the rate of thinning in visual cortex nor the reduction in white matter integrity during the ~ 2-year period reached significance. We also measured cortical myelin density; cross-sectional data showed this was higher in patients than controls, likely as a result of greater thinning of non-myelinated tissue in patients. However, we also found evidence of a greater rate of loss of myelin density in the occipital pole in the patient group indicating that the posterior visual pathway is at risk in established MD. Taken together, our results revealed a broad decline in grey and white matter in the posterior visual pathway in bilateral MD; cortical thickness and fractional anisotropy show hints of an accelerated rate of loss also, with larger effects emerging in the occipital pole.},
}
@article {pmid36972567,
year = {2023},
author = {Popovic, MM and Sheidow, T and Baker, J and Kertes, PJ},
title = {Maximal Extension Interval and Visual Outcomes in a Treat-and-Extend Protocol: A Post Hoc Analysis of the CANTREAT Randomized Trial.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {2},
pages = {123-130},
doi = {10.1159/000530364},
pmid = {36972567},
issn = {1423-0267},
mesh = {Humans ; *Ranibizumab ; Angiogenesis Inhibitors ; Treatment Outcome ; Prospective Studies ; Canada ; Intravitreal Injections ; Tomography, Optical Coherence ; *Wet Macular Degeneration/diagnosis/drug therapy ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; },
abstract = {INTRODUCTION: The Canadian Treat-and-Extend Analysis Trial with Ranibizumab (CANTREAT) was a 2-year, multicentred, randomized clinical trial to evaluate treat-and-extend (T&amp;E) relative to monthly administration of ranibizumab in neovascular age-related macular degeneration (nAMD). This post hoc analysis of the CANTREAT trial explores the relationship between the maximal extension interval tolerated by patients receiving T&amp;E ranibizumab and visual acuity outcomes.<br><br>METHODS: Treatment-na&#xef;ve patients with nAMD were randomized to receive either a once-monthly dosing or T&amp;E regimen of ranibizumab across 27 treatment centres in Canada and were followed for 24 months. For this post hoc analysis, patients in the T&amp;E cohort were subdivided into the following groups based on maximum extension interval: 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks. The primary outcome was the change in ETDRS best-corrected visual acuity (BCVA) from baseline to month 24 while secondary outcomes included change in central retinal thickness (CRT). All results were reported using descriptive statistics.<br><br>RESULTS: A total of 285 participants undergoing T&amp;E were enrolled in this post hoc analysis. At month 24, the change in BCVA from baseline was +8.5 &#xb1; 9.3, +7.7 &#xb1; 13.8, +4.4 &#xb1; 9.6, +4.4 &#xb1; 18.5, and +7.8 &#xb1; 14.8 letters in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. The change in CRT at month 24 was -79.2 &#xb1; 95.0, -143.9 &#xb1; 128.9, -97.7 &#xb1; 101.1, -120.9 &#xb1; 105.3, and -133.2 &#xb1; 108.8 &#x3bc;m in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively.<br><br>CONCLUSION: The capacity to extend does not necessarily associate with improved visual acuity outcomes, with the poorest change in BCVA seen in those extended 8-10 weeks. The highest change in BCVA and lowest decrease in CRT was in the group maximally extended for 4 weeks. There was a correlation between change in BCVA and change in CRT for other extension groups. Future studies should establish the predictive factors for successful extension in patients undergoing T&amp;E in nAMD.},
}
@article {pmid36971800,
year = {2023},
author = {Sotani, R and Matsumiya, W and Kim, KW and Miki, A and Yasuda, E and Maeda, Y and Hara, R and Kusuhara, S and Nakamura, M},
title = {Clinical features and associated factors of intraocular inflammation following intravitreal brolucizumab as switching therapy for neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {8},
pages = {2359-2366},
pmid = {36971800},
issn = {1435-702X},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Retrospective Studies ; Fluorescein Angiography ; *Uveitis/drug therapy ; *Macular Degeneration/drug therapy ; Inflammation ; Atrophy/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: The aim of this study is to explore the clinical features and associated factors of intraocular inflammation (IOI) following intravitreal brolucizumab (IVBr) administration for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This retrospective study included 87 eyes from 87 Japanese patients with nAMD who were followed up for 5&#xa0;months after the initial administration of IVBr as switching therapy. Clinical pictures of IOI post-IVBr and changes in best corrected visual acuity (BCVA) at 5&#xa0;months were evaluated between eyes with and without IOI (non-IOI). The association between IOI and baseline factors (age, sex, BCVA, hypertension, and/or arteriosclerotic changes in the fundus, subretinal hyperreflective material [SHRM], and macular atrophy) was evaluated.<br><br>RESULTS: Of the 87 eyes, 18 (20.6%) developed IOI and 2 (2.3%) developed retinal artery occlusion. There were 9 (50%) cases of posterior or pan-uveitis among eyes with IOI. The mean interval from initial IVBr administration to IOI was 2&#xa0;months. The mean changes in logMAR BCVA at 5&#xa0;months were significantly worse in IOI eyes than in non-IOI eyes (0.09&#x2009;&#xb1;&#x2009;0.22 vs.&#x2009;-&#x2009;0.01&#x2009;&#xb1;&#x2009;0.15, P&#x2009;=&#x2009;0.03). There were 8 (44.4%) and 7 (10.1%) cases of macular atrophy and 11 (61.1%) and 13 (18.8%) cases of SHRM in the IOI and non-IOI groups, respectively. SHRM and macular atrophy were significantly associated with IOI (P&#x2009;=&#x2009;0.0008 and P&#x2009;=&#x2009;0.002, respectively).<br><br>CONCLUSION: In IVBr therapy for nAMD, eyes with SHRM and/or macular atrophy should be observed more meticulously, given the increased risk of developing IOI, which is associated with insufficient BCVA gain.},
}
@article {pmid36971785,
year = {2023},
author = {Alghamdi, A and Keegan, D and Connell, P and Dooley, I and O'Toole, L},
title = {Adherence of patients with age-related macular degeneration to AREDS 2-recommended nutritional supplements.},
journal = {Irish journal of medical science},
volume = {192},
number = {6},
pages = {3163-3167},
pmid = {36971785},
issn = {1863-4362},
mesh = {Humans ; *Antioxidants ; Angiogenesis Inhibitors ; Referral and Consultation ; Visual Acuity ; Vascular Endothelial Growth Factor A ; Telephone ; *Wet Macular Degeneration ; Dietary Supplements ; Disease Progression ; },
abstract = {BACKGROUND: The Age-Related Eye Disease Study 2 (AREDS 2) proved the benefit of vitamin and mineral supplementation in preventing advanced age-related macular degeneration (AMD). AREDS 2 supplements are indicated for patients with either bilateral intermediate AMD (AREDS category 3) or unilateral neovascular AMD (AREDS category 4).<br><br>AIMS: The aims of this telephone survey were to identify the rate of adherence of patients to AREDS 2 supplements and the factors associated with non-compliance in these patient groups.<br><br>METHODS: A patient telephone survey was conducted in an Irish tertiary care hospital. Patients were identified by chart review, and their AREDS categorization was reconfirmed. A telephone consultation was conducted with each patient to assess their compliance with the micronutrient supplements.<br><br>RESULTS: We identified 120 patients who met the AREDS criteria for supplementation. Of these, 103 patients were graded as category 4, and 17 patients were graded as category 3. Almost a fifth (18%) were current smokers. Under two-thirds (60%) of the patients were taking AREDS 2 supplements. Of the remainder, 83% of patients did not recall being advised of their benefit. The cost was cited by 10% of patients as a reason for non-compliance.<br><br>CONCLUSION: The ophthalmologist not only has a duty of care to treat the neovascular complications of AMD, but they must also strive to improve patient compliance with AREDS supplements. The cessation of smoking needs to be actively promoted in order to stop preventable vision loss in patients with AMD.},
}
@article {pmid36971708,
year = {2023},
author = {Chen, LJ and Chen, ZJ and Pang, CP},
title = {Latest Development on Genetics of Common Retinal Diseases.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {2},
pages = {228-251},
doi = {10.1097/APO.0000000000000592},
pmid = {36971708},
issn = {2162-0989},
mesh = {Humans ; Artificial Intelligence ; Genome-Wide Association Study ; *Macular Degeneration/drug therapy ; Choroid/blood supply ; *Choroid Diseases ; Fluorescein Angiography ; *Choroidal Neovascularization/drug therapy ; },
abstract = {Many complex forms of retinal diseases are common and pan-ethnic in occurrence. Among them, neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and central serous choroid retinopathy involve both choroidopathy and neovascularization with multifactorial etiology. They are sight-threatening and potentially blinding. Early treatment is crucial to prevent disease progression. To understand their genetic basis, candidate gene mutational and association analyses, linkage analysis, genome-wide association studies, transcriptome analysis, next-generation sequencing, which includes targeted deep sequencing, whole-exome sequencing, and whole genome sequencing have been conducted. Advanced genomic technologies have led to the identification of many associated genes. But their etiologies are attributed to complicated interactions of multiple genetic and environmental risk factors. Onset and progression of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy are affected by aging, smoking, lifestyle, and variants in over 30 genes. Although some genetic associations have been confirmed and validated, individual genes or polygenic risk markers of clinical value have not been established. The genetic architectures of all these complex retinal diseases that involve sequence variant quantitative trait loci have not been fully delineated. Recently artificial intelligence is making an impact in the collection and advanced analysis of genetic, investigative, and lifestyle data for the establishment of predictive factors for the risk of disease onset, progression, and prognosis. This will contribute to individualized precision medicine for the management of complex retinal diseases.},
}
@article {pmid36971707,
year = {2023},
author = {Horie, S and Corradetti, G and Esmaeilkhanian, H and Sadda, SR and Cheung, CMG and Ham, Y and Chang, A and Takahashi, T and Ohno-Matsui, K},
title = {Microperimetry in Retinal Diseases.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {2},
pages = {211-227},
pmid = {36971707},
issn = {2162-0989},
mesh = {Humans ; *Macular Edema ; *Diabetic Retinopathy ; Visual Field Tests/methods ; Retina ; *Retinal Diseases/diagnosis ; *Macular Degeneration/diagnosis ; Tomography, Optical Coherence ; },
abstract = {Retinal microperimetry (MP) is a procedure that assesses the retinal sensitivity while the fundus is directly observed, and an eye tracker system is active to compensate for involuntary eye movements during testing. With this system, the sensitivity of a small locus can be accurately determined, and it has become an established ophthalmic test for retinal specialists. Macular diseases are characterized by chorioretinal changes; therefore, the condition of the retina and choroid requires careful and detailed evaluations to perform effective therapy. Age-related macular degeneration is a representative retinal disease in which the macular function has been evaluated by the visual acuity throughout the course of the disease process. However, the visual acuity represents the physiological function of only the central fovea, and the function of the surrounding macular area has not been sufficiently evaluated throughout the different stages of the macula disease process. The new technique of MP can compensate for such limitations by being able to test the same sites of the macular area repeatedly. This is especially useful in the recent management of age-related macular degeneration or diabetic macular edema during anti-vascular endothelial growth factor treatments because MP can assess the effectiveness of the treatment. MP examinations are also valuable in diagnosing Stargardt disease as they can detect visual impairments before any abnormalities are found in the retinal images. The visual function needs to be carefully assessed along with morphologic observations by optical coherence tomography. In addition, the assessment of retinal sensitivity is useful in the presurgical or postsurgical evaluations.},
}
@article {pmid36971706,
year = {2023},
author = {Radke, NV and Mohamed, S and Brown, RB and Ibrahim, I and Chhablani, J and Amin, SV and Tsang, CW and Brelen, ME and Raichand, NS and Fang, D and Zhang, S and Dai, H and Chen, GLJ and Cheung, CMG and Hariprasad, SM and Das, T and Lam, DSC},
title = {Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {2},
pages = {168-183},
doi = {10.1097/APO.0000000000000602},
pmid = {36971706},
issn = {2162-0989},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy ; Endothelial Growth Factors/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Uveitis/drug therapy ; Inflammation ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {Frequent antivascular endothelial growth factor injections in neovascular age-related macular degeneration (nAMD) often lead to poor compliance and suboptimal outcomes. A longer-acting agent has been a pressing unmet need until recently. Brolucizumab, an antivascular endothelial growth factor agent, is a single-chain antibody fragment approved by the US Food and Drug Administration (FDA) on October 8, 2019, for treating nAMD. It delivers more molecules at equivalent volumes of aflibercept, thus achieving a longer-lasting effect. We reviewed literature published in English between January 2016 and October 2022 from MEDLINE, PubMed, Cochrane database, Embase, and Google scholar using the keywords: "Brolucizumab, real-world data, intraocular inflammation (IOI), safety, and efficacy". Brolucizumab showed reduced injection frequency, better anatomic outcomes, and noninferior vision gains compared with aflibercept in HAWK and HARRIER studies. However, post hoc studies on brolucizumab revealed a higher-than-expected incidence of IOI, leading to the early termination of 3 studies: MERLIN, RAPTOR, and RAVEN for nAMD, branch retinal vein occlusion, and central retinal vein occlusion, respectively. Contrastingly real-world data showed encouraging outcomes in terms of fewer IOI cases. The subsequent amendment of the treatment protocol resulted in reduced IOI. Thereafter US FDA approved its use in diabetic macular edema on June 1, 2022. Based on major studies and real-world data, this review shows that brolucizumab is effective for treating naive and refractory nAMD. The risk of IOI is acceptable and manageable, but proper preinjection screening and high-vigilance care of IOI are needed. More studies are warranted to evaluate further the incidence, best prevention, and treatment measures for IOI.},
}
@article {pmid36971449,
year = {2023},
author = {Landowski, M and Grindel, S and Hao, Y and Ikeda, S and Bowes Rickman, C and Ikeda, A},
title = {A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {193},
pages = {},
pmid = {36971449},
issn = {1940-087X},
support = {P30 EY005722/EY/NEI NIH HHS/United States ; P30 EY016665/EY/NEI NIH HHS/United States ; S10 OD023526/OD/NIH HHS/United States ; F32 EY032766/EY/NEI NIH HHS/United States ; R01 EY022086/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; T32 EY027721/EY/NEI NIH HHS/United States ; R01 EY031748/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; Mice, Inbred C57BL ; *Macular Degeneration/pathology ; Retinal Pigment Epithelium/metabolism ; Retina/metabolism ; Disease Models, Animal ; Epithelium/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a debilitating retinal disorder in aging populations. It is widely believed that dysfunction of the retinal pigmented epithelium (RPE) is a key pathobiological event in AMD. To understand the mechanisms that lead to RPE dysfunction, mouse models can be utilized by researchers. It has been established by previous studies that mice can develop RPE pathologies, some of which are observed in the eyes of individuals diagnosed with AMD. Here, we describe a phenotyping protocol to assess RPE pathologies in mice. This protocol includes the preparation and evaluation of retinal cross-sections using light microscopy and transmission electron microscopy, as well as that of RPE flat mounts by confocal microscopy. We detail the common types of murine RPE pathologies observed by these techniques and ways to quantify them through unbiased methods for statistical testing. As proof of concept, we use this RPE phenotyping protocol to quantify the RPE pathologies observed in mice overexpressing transmembrane protein 135 (Tmem135) and aged wild-type C57BL/6J mice. The main goal of this protocol is to present standard RPE phenotyping methods with unbiased quantitative assessments for scientists using mouse models of AMD.},
}
@article {pmid36970117,
year = {2023},
author = {Berlin, A and Cabral, D and Chen, L and Messinger, JD and Balaratnasingam, C and Mendis, R and Ferrara, D and Freund, KB and Curcio, CA},
title = {Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration: A Case Study.},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100280},
pmid = {36970117},
issn = {2666-9145},
abstract = {PURPOSE: To investigate intraretinal neovascularization and microvascular anomalies by correlating in vivo multimodal imaging with corresponding ex vivo histology in a single patient.<br><br>DESIGN: A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation).<br><br>PARTICIPANTS: A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD).<br><br>METHODS: Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy.<br><br>MAIN OUTCOME MEASURES: Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging.<br><br>RESULTS: Six vascular lesions were histologically confirmed (type 3 MNV, n&#xa0;= 3; deep retinal age-related microvascular anomalies [DRAMAs], n&#xa0;= 3). Pyramidal (n&#xa0;= 2) or tangled (n&#xa0;= 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)-basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes.<br><br>CONCLUSIONS: Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36970115,
year = {2023},
author = {Chen, S and Abu-Qamar, O and Kar, D and Messinger, JD and Hwang, Y and Moult, EM and Lin, J and Baumal, CR and Witkin, A and Liang, MC and Waheed, NK and Curcio, CA and Fujimoto, JG},
title = {Ultrahigh Resolution OCT Markers of Normal Aging and Early Age-related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100277},
pmid = {36970115},
issn = {2666-9145},
support = {R01 EY011289/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Ultrahigh resolution spectral domain-OCT (UHR SD-OCT) enables in vivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging.<br><br>DESIGN: Prospective cross-sectional study.<br><br>PARTICIPANTS: A total of 53 nonexudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects.<br><br>METHODS: Clinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hyporeflective split within the RPE-RPE basal lamina (RPE-BL)-Bruch's membrane (BrM) complex on UHR brightness (B)-scans. A semi-automatic segmentation algorithm measured the thickness of the RPE-BL-BrM split/hyporeflective band.<br><br>MAIN OUTCOME MEASURES: Qualitative description of outer retinal morphological changes on UHR SD-OCT B-scans; the proportion of the RPE-BL-BrM complex with visible split (%) and the thickness of the resulting hyporeflective band (&#x3bc;m).<br><br>RESULTS: In young normal eyes, UHR SD-OCT consistently revealed an RPE-BL-BrM split/hyporeflective band. Its visibility and thickness were less in eyes of advanced age. However, the split/hyporeflective band was again visible in early AMD eyes. Both qualitative reading and quantitative thickness measurements showed significantly elevated visibility and thickness of the RPE-BL-BrM split/hyporeflective in early AMD eyes compared to age-matched controls.<br><br>CONCLUSIONS: Our imaging results strongly support the hypothesis that appearance of the RPE-BL-BrM split/hyporeflective band in older subjects is dominated by the BL deposit, an indicator of early AMD well known from histology. Ultrahigh resolution SD-OCT can be used to investigate physiological aging as well as early AMD pathology in clinical imaging studies. Developing quantifiable markers associated with disease pathogenesis and progression can facilitate drug discovery, as well as reduce clinical trial times.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36969592,
year = {2023},
author = {Chu-Tan, JA and Cioanca, AV and Wooff, Y and Kirkby, M and Ellis, M and Gulati, P and Karl, T and Boatright, JH and Bales, K and Nickerson, J and Natoli, R},
title = {Voluntary exercise modulates pathways associated with amelioration of retinal degenerative diseases.},
journal = {Frontiers in physiology},
volume = {14},
number = {},
pages = {1116898},
pmid = {36969592},
issn = {1664-042X},
support = {R01 EY028859/EY/NEI NIH HHS/United States ; P30 EY006360/EY/NEI NIH HHS/United States ; I21 RX001924/RX/RRD VA/United States ; IK2 BX005304/BX/BLRD VA/United States ; I01 RX002806/RX/RRD VA/United States ; },
abstract = {Background: Exercise has been shown to promote a healthier and longer life and linked to a reduced risk of developing neurodegenerative diseases including retinal degenerations. However, the molecular pathways underpinning exercise-induced cellular protection are not well understood. In this work we aim to profile the molecular changes underlying exercise-induced retinal protection and investigate how exercise-induced inflammatory pathway modulation may slow the progression of retinal degenerations. Methods: Female C57Bl/6J mice at 6 weeks old were given free access to open voluntary running wheels for a period of 28 days and then subjected to 5 days of photo-oxidative damage (PD)-induced retinal degeneration. Following, retinal function (electroretinography; ERG), morphology (optical coherence tomography; OCT) and measures of cell death (TUNEL) and inflammation (IBA1) were analysed and compared to sedentary controls. To decipher global gene expression changes as a result of voluntary exercise, RNA sequencing and pathway and modular gene co-expression analyses were performed on retinal lysates of exercised and sedentary mice that were subjected to PD, as well as healthy dim-reared controls. Results: Following 5 days of PD, exercised mice had significantly preserved retinal function, integrity and reduced levels of retinal cell death and inflammation, compared to sedentary controls. In response to voluntary exercise, inflammatory and extracellular matrix integrity pathways were significantly modulated, with the gene expression profile of exercised mice more closely trending towards that of a healthy dim-reared retina. Conclusion: We suggest that voluntary exercise may mediate retinal protection by influencing key pathways involved in regulating retinal health and shifting the transcriptomic profile to a healthy phenotype.},
}
@article {pmid36968207,
year = {2023},
author = {Song, S and Jin, K and Wang, S and Yang, C and Zhou, J and Chen, Z and Ye, J},
title = {Retinal fluid is associated with cytokines of aqueous humor in age-related macular degeneration using automatic 3-dimensional quantification.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1157497},
pmid = {36968207},
issn = {2296-634X},
abstract = {Background: To explain the biological role of cytokines in the eye and the possible role of cytokines in the pathogenesis of neovascular age-related macular degeneration (nAMD) by comparing the correlation between cytokine of aqueous humor concentration and optical coherence tomography (OCT) retinal fluid. Methods: Spectral-domain OCT (SD-OCT) images and aqueous humor samples were collected from 20 nAMD patient's three clinical visits. Retinal fluid volume in OCT was automatically quantified using deep learning--Deeplabv3+. Eighteen cytokines were detected in aqueous humor using the Luminex technology. OCT fluid volume measurements were correlated with changes in aqueous humor cytokine levels using Pearson's correlation coefficient (PCC). Results: The patients with intraretinal fluid (IRF) showed significantly lower levels of cytokines, such as C-X-C motif chemokine ligand 2 (CXCL2) (p = 0.03) and CXCL11 (p = 0.009), compared with the patients without IRF. And the IRF volume was negatively correlated with CXCL2 (r = -0.407, p = 0.048) and CXCL11 (r = -0.410, p = 0.046) concentration in the patients with IRF. Meanwhile, the subretinal fluid (SRF) volume was positively correlated with vascular endothelial growth factor (VEGF) concentration (r = 0.299, p = 0.027) and negatively correlated with interleukin (IL)-36β concentration (r = -0.295, p = 0.029) in the patients with SRF. Conclusion: Decreased level of VEGF was associated with decreased OCT-based retinal fluid volume in nAMD patients, while increased levels of CXCL2, CXCL11, and IL-36β were associated with decreased OCT-based retinal fluid volume in nAMD patients, which may suggest a role for inflammatory cytokines in retinal morphological changes and pathogenesis of nAMD patients.},
}
@article {pmid36966949,
year = {2023},
author = {Park, JG and Chen, XD and Clontz, M and Begaj, T and Runner, MM and Wolfe, JD},
title = {Coding of Geographic Atrophy and Exudative Age-related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {7},
pages = {644-645},
doi = {10.1016/j.oret.2023.03.011},
pmid = {36966949},
issn = {2468-6530},
mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Macular Degeneration/complications/diagnosis ; Tomography, Optical Coherence ; },
}
@article {pmid36964259,
year = {2023},
author = {Patel, SS and Lally, DR and Hsu, J and Wykoff, CC and Eichenbaum, D and Heier, JS and Jaffe, GJ and Westby, K and Desai, D and Zhu, L and Khanani, AM},
title = {Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial.},
journal = {Eye (London, England)},
volume = {37},
number = {17},
pages = {3551-3557},
pmid = {36964259},
issn = {1476-5454},
mesh = {Humans ; *Geographic Atrophy/drug therapy/etiology ; Prospective Studies ; Visual Acuity ; *Macular Degeneration/complications/drug therapy ; Intravitreal Injections ; Fluorescein Angiography ; },
abstract = {BACKGROUND/OBJECTIVES: To assess the safety and efficacy of avacincaptad pegol (ACP), a C5 inhibitor, for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) over an 18-month treatment course.<br><br>SUBJECTS/METHODS: This study was an international, prospective, randomized, double-masked, sham-controlled, phase 2/3 clinical trial that consisted of 2 parts. In part 1, 77 participants were randomized 1:1:1 to receive monthly intravitreal injections of ACP 1&#x2009;mg, ACP 2&#x2009;mg, or sham. In part 2, 209 participants&#xa0;were randomized 1:2:2 to receive monthly ACP 2&#x2009;mg, ACP 4&#x2009;mg, or sham. The mean rate of change of GA over 18 months was measured by fundus autofluorescence.<br><br>RESULTS: Compared with their respective sham cohorts, monthly ACP treatment reduced the mean GA growth (square root transformation) over 18 months by 28.1% (0.168&#x2009;mm, 95% CI [0.066, 0.271]) for the 2&#x2009;mg cohort and 30.0% (0.167&#x2009;mm, 95% CI [0.062, 0.273]) for the 4&#x2009;mg cohort. ACP treatment was generally well tolerated over 18 months, with most ocular adverse events (AEs) related to the injection procedure. Macular neovascularization (MNV) was more frequent in both 2&#x2009;mg (11.9%) and 4&#x2009;mg (15.7%) cohorts than their respective sham control groups (2.7% and 2.4%).<br><br>CONCLUSIONS: Over this 18-month study, ACP 2&#x2009;mg and 4&#x2009;mg showed continued reductions in the progression of GA growth compared to sham and continued to be generally well tolerated. A pivotal phase 3 GATHER2 trial is currently underway to support the efficacy and safety of ACP as a potential treatment for GA.},
}
@article {pmid36960325,
year = {2023},
author = {Bakaliou, A and Georgakopoulos, C and Tsilimbaris, M and Farmakakis, N},
title = {Posterior Vitreous Detachment and Its Role in the Evolution of Dry to Wet Age Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {879-885},
pmid = {36960325},
issn = {1177-5467},
abstract = {PURPOSE: To examine the state of the posterior vitreous in eyes with exudative age-related macular degeneration, AMD, non-exudative AMD and in normal eyes.<br><br>STUDY: This is a prospective, cross-sectional study.<br><br>METHODS: B-scan ultrasonography and Optical Coherence Tomography, OCT were performed in 165 patients older than 65 years with any AMD and in 22 patients older than 65 years with normal eyes in order to diagnose the eyes with complete posterior vitreous detachment, PVD and the eyes with persistent central vitreomacular adhesion, VMA. All patients were selected from the outpatient clinic of the Ophthalmology Department in the University Hospital of Patras. Fundus Fluoroangiography, FFA was used in order to determine the development of exudative AMD from non-exudative AMD. Follow up time was 48 months.<br><br>RESULTS: 16/171 eyes with exudative AMD (9.36%) had complete PVD, and the rest 155/171 (90.64%) had central VMA. Eleven of 138 eyes with non-exudative AMD (7.97%) had complete PVD and the remaining 127 eyes (92.03%) had central VMA. During the 48 months of the study, 28 eyes, all with central VMA progressed to exudative AMD.<br><br>CONCLUSION: Vitreomacular adhesion is associated with both exudative and non-exudative AMD. Progression of the non-exudative eyes to exudative AMD seems to be lower in eyes with complete PVD. On the other hand, the progression of normal eyes to exudative AMD appears to be independent of the posterior vitreous status. Larger and longer studies need to replicate these findings and support the potential of a protective role of complete posterior vitreous detachment in the evolution of the disease.},
}
@article {pmid36959460,
year = {2023},
author = {Fukuyama, H and BouGhanem, G and Moir, J and Skondra, D and Gomi, F and Fawzi, AA},
title = {Clinical variations of polypoidal choroidal vasculopathy: A cohort study from Japan and the USA.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {4800},
pmid = {36959460},
issn = {2045-2322},
support = {R01 EY019951/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Choroid Diseases/drug therapy ; Choroid/blood supply ; Cohort Studies ; Retrospective Studies ; Polypoidal Choroidal Vasculopathy ; Japan/epidemiology ; Fluorescein Angiography ; *Retinal Drusen/pathology ; Tomography, Optical Coherence ; *Polyps/diagnosis/epidemiology/pathology ; *Choroidal Neovascularization/diagnosis/epidemiology/drug therapy ; },
abstract = {We describe the clinical characteristics of treatment-naïve polypoidal choroidal vasculopathy (PCV) in three tertiary clinic settings in 2 cities (Chicago in the USA and Nishinomiya in Japan). This cohort study was a retrospective, multicenter, consecutive case series. A total of 126 patients with treatment-naïve PCV-46 in Chicago and 80 in Nishinomiya-were identified. The proportion of PCV in patients with neovascular age-related macular degeneration was lower in Chicago (10.8% vs. 36.9%). Patients in Chicago had a significantly higher prevalence of soft drusen (50.0% vs 25.0%, p = 0.006) and intra-retinal cyst (37.0% vs 15.0%, p = 0.008), and a significantly lower prevalence of pachyvessels (41.3% vs 62.5%, p = 0.03). At baseline, presenting vision for patients in Chicago was worse than in Nishinomiya (mean log MAR: 0.609 vs. 0.312, p < 0.001). Ninety-five eyes were followed for more than one year. The Nishinomiya group received a higher rate of combination therapy (61.0%) compared to the Chicago group (5.3%). Vision and central foveal thickness at month 12 were significantly improved from baseline in both Chicago (p = 0.009 and p = 0.01) and Nishinomiya groups (both p < 0.001). Our study highlights interesting differences in the proportion of PCV, clinical findings and treatment responses of PCV, that need to be further evaluated in larger, epidemiologic cohorts.},
}
@article {pmid36959312,
year = {2023},
author = {Stanga, PE and Valentín-Bravo, FJ and Stanga, SEF and Reinstein, UI and Pastor-Idoate, S and Downes, SM},
title = {Faricimab in neovascular AMD: first report of real-world outcomes in an independent retina clinic.},
journal = {Eye (London, England)},
volume = {37},
number = {15},
pages = {3282-3289},
pmid = {36959312},
issn = {1476-5454},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; Aged ; *Visual Acuity/physiology ; *Tomography, Optical Coherence ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; *Angiogenesis Inhibitors/therapeutic use/administration &amp; dosage ; Aged, 80 and over ; Fluorescein Angiography ; Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; Treatment Outcome ; Middle Aged ; },
abstract = {PURPOSE: Assess short-term real-world outcomes in neovascular aged-related macular degeneration (nAMD) treated with novel faricimab.<br><br>METHODS: Retrospective case series of nine patients with nAMD (11 eyes) treated with faricimab between May and November 2022. Treatment-na&#xef;ve patients and non-na&#xef;ve patients underwent logMAR best corrected visual acuity (BCVA), optical coherence tomography (OCT) DRI OCT-1 Triton (Topcon Corp, Tokyo, Japan), ultra-widefield (UWF) and fundus autofluorescence (FAF) (California Optomap, Optos plc, Dunfermline, Scotland, UK). Previous treatment intervals, number of intravitreal injections, sub/intra retinal fluid (SRF/IRF), central retinal thickness (CRT) and presence/changes in pigment epithelial detachments (PEDs) were recorded.<br><br>RESULTS: Mean baseline BCVA and CRT values of patients who switched from other agents were 0.612&#x2009;&#xb1;&#x2009;0.75 logMAR and 256.16&#x2009;&#xb1;&#x2009;12.98&#x2009;&#xb5;m respectively, with a mean 36-day previous treatment interval. The median number of other previous anti-VEGF intravitreal injections was 8. Mean BCVA at one month significantly improved to 0.387&#x2009;&#xb1;&#x2009;0.54 logMAR, as well as CRT values which decreased to 245.43&#x2009;&#xb1;&#x2009;15.34&#x2009;&#xb5;m. In the 3 na&#xef;ve patients, mean baseline BVCA and CRT values were 0.33&#x2009;&#xb1;&#x2009;0.29 and 874.67&#x2009;&#xb1;&#x2009;510.86&#x2009;&#xb5;m, respectively. At one month follow-up, mean BCVA improved to 0.30&#x2009;&#xb1;&#x2009;0.29 logMAR and mean CRT was 536.04&#x2009;&#xb1;&#x2009;36.15&#x2009;&#xb5;m. Overall, a significant improvement in BCVA of 0.21&#x2009;&#xb1;&#x2009;41 logMAR and 238.44&#x2009;&#xb1;&#x2009;114.9&#x2009;&#xb5;m was achieved at one month after the first faricimab intravitreal injection. In addition, a complete resolution of SRF was observed in 6 out of 8 eyes (75%) and of IRF in 2 out of 3 eyes (66.67%), respectively. Drusenoid PED morphology changes were observed in all patients and no drug-related adverse events were observed.<br><br>CONCLUSION: Real-world outcomes showed improvement in BCVA and anatomic parameters at an early timepoint, demonstrating the efficacy and durability of faricimab in nAMD patients. Larger numbers of patients and longer follow-up are needed to determine whether the loading dose is required in all, what percentage of patients experience an improvement, and whether improvement it is maintained.},
}
@article {pmid36958537,
year = {2023},
author = {Liu, J and Shen, M and Laiginhas, R and Herrera, G and Li, J and Shi, Y and Hiya, F and Trivizki, O and Waheed, NK and Chung, CY and Moult, EM and Fujimoto, JG and Gregori, G and Rosenfeld, PJ},
title = {Onset and Progression of Persistent Choroidal Hypertransmission Defects in Intermediate Age-Related Macular Degeneration: A Novel Clinical Trial Endpoint.},
journal = {American journal of ophthalmology},
volume = {254},
number = {},
pages = {11-22},
pmid = {36958537},
issn = {1879-1891},
support = {P30 EY014801/EY/NEI NIH HHS/United States ; R01 EY011289/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Disease Progression ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis ; Prospective Studies ; Retina ; Clinical Trials as Topic ; },
abstract = {PURPOSE: The appearance and growth of persistent choroidal hypertransmission defects (hyperTDs) detected on en face swept-source optical coherence tomography (SS-OCT) images from eyes with intermediate age-related macular degeneration (iAMD) were studied to determine if they could serve as novel clinical trial endpoints.<br><br>DESIGN: Post hoc subgroup analysis of a prospective study.<br><br>METHODS: Subjects with iAMD underwent 6&#xa0;&#xd7;&#xa0;6 mm SS-OCT angiography imaging at their baseline and follow-up visits. The drusen volumes were obtained using a validated SS-OCT algorithm. Two graders independently evaluated all en face structural images for the presence of persistent hyperTDs. The number and area of all hyperTDs along with drusen volume were obtained from all SS-OCT angiography scans. Eyes were censored from further follow-up once exudative AMD developed.<br><br>RESULTS: A total of 171 eyes from 121 patients with iAMD were included. Sixty-eight eyes developed at least 1 hyperTD. Within 1 year after developing a hyperTD, 25% of eyes developed new hyperTDs for an average of 0.44 additional hyperTDs. Over 2 years, as hyperTDs appeared, enlarged, and merged, the average area growth rate was 0.220 mm/yr using the square-root transformation strategy. A clinical trial design using the onset and enlargement of these hyperTDs for the study of disease progression in eyes with iAMD is proposed.<br><br>CONCLUSIONS: The appearance and growth of persistent choroidal hyperTDs in eyes with iAMD can be easily detected and measured using en face OCT imaging and can serve as novel clinical trial endpoints for the study of therapies that may slow disease progression from iAMD to late AMD.},
}
@article {pmid36952520,
year = {2023},
author = {Sun, W and Zhao, Y and Liao, L and Wang, X and Wei, Q and Chao, G and Zhou, J},
title = {Effects of acupuncture on age-related macular degeneration: A systematic review and meta-analysis of randomized controlled trials.},
journal = {PloS one},
volume = {18},
number = {3},
pages = {e0283375},
pmid = {36952520},
issn = {1932-6203},
mesh = {Humans ; Randomized Controlled Trials as Topic ; *Macular Degeneration/drug therapy ; Eye ; *Geographic Atrophy ; *Acupuncture Therapy ; },
abstract = {BACKGROUND: In recent years, an increasing number of patients with age-related macular degeneration (AMD) have received acupuncture treatment, but there has been no systematic review to evaluate the effect of acupuncture on patients with AMD.<br><br>PURPOSE: This meta-analysis aims to review the clinical efficacy of acupuncture in the treatment of AMD.<br><br>METHODS: Randomized controlled trials up to September 4, 2022 were searched in the following databases: PubMed, Ovid Medline, Embase, Cochrane Library, The Chinese National Knowledge Infrastructure Database, VIP, Wanfang, and SINOMED. Two reviewers independently performed literature screening and data extraction. RevMan 5.4 was used for the meta-analysis.<br><br>RESULTS: Nine of the 226 articles were finally included. A total of 508 AMD patients (631 eyes) were enrolled, including 360 dry eyes and 271 wet eyes. The results showed that acupuncture alone or as an adjunct therapy improved both the clinical efficacy and best-corrected visual acuity (BCVA) of AMD patients and reduced their central macular thickness. The certainty of the evidence ranged from "low" to "very low".<br><br>CONCLUSION: There is no high-quality evidence that acupuncture is effective in treating patients with AMD; patients with dry AMD may benefit from acupuncture treatment. Considering the potential of acupuncture treatment for AMD, it is necessary to conduct a rigorously designed randomized controlled trials to verify its efficacy.},
}
@article {pmid36952338,
year = {2023},
author = {Orozco, LD and Chen, HH and Cox, C and Katschke, KJ and Rommel Arceo, and Espiritu, C and Caplazi, P and Nghiem, SS and Chen, YJ and Modrusan, Z and Dressen, A and Goldstein, LD and Clarke, C and Bhangale, T and Yaspan, B and Jeanne, M and Townsend, MJ and van Lookeren Campagne, M and Hackney, JA},
title = {Integration of eQTL and a Single-Cell Atlas in the Human Eye Identifies Causal Genes for Age-Related Macular Degeneration.},
journal = {Cell reports},
volume = {42},
number = {3},
pages = {112298},
doi = {10.1016/j.celrep.2023.112298},
pmid = {36952338},
issn = {2211-1247},
}
@article {pmid36951828,
year = {2023},
author = {Hou, X and Zhang, X and Zhang, Z},
title = {Case Report: Asymmetric Changes of Ophthalmic Findings in Bilateral Solar Eclipse Maculopathy.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {100},
number = {5},
pages = {339-345},
doi = {10.1097/OPX.0000000000002012},
pmid = {36951828},
issn = {1538-9235},
mesh = {Male ; Humans ; Young Adult ; Adult ; *Retinal Diseases/diagnosis ; Retina ; Retinal Pigment Epithelium ; *Macular Degeneration ; Visual Acuity ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; },
abstract = {SIGNIFICANCE: A more profound understanding of the relationship between ophthalmic findings and eye dominance is needed to guide the timely and proper treatment of binocular photic maculopathy or other macular degeneration.<br><br>PURPOSE: A patient with binocular solar maculopathy presented with asymmetric ophthalmic manifestations and changes during 14 months of observation. Early recognition of solar maculopathy can be vital for early diagnosis and better prognosis.<br><br>CASE REPORT: A 21-year-old man was reported to have blurred vision after staring directly at an annular solar eclipse several times for a few seconds on June 21, 2020. His Snellen best-corrected visual acuity declined to 20/50 in both eyes. He was right-eye dominant according to the hole-in-the-card test. The funduscopy found a yellow spot in the center of both maculae. Spectral-domain optical coherence tomography images revealed a full-thickness hyperreflectivity extending from the inner retinal layers to the retinal pigment epithelium (RPE) along with a localized disruption of the ellipsoid portion of the inner segments and RPE in both eyes. The medical history and clinical manifestations described previously supported the diagnosis of solar maculopathy. Spectral-domain optical coherence tomography images during follow-up indicated a diminishing disruption of the ellipsoid portion of the inner segments and RPE without treatment. Interestingly, the nondominant left eye made a better anatomical recovery. Finally, the Snellen best-corrected visual acuity remained 20/20 in both eyes after 14 months.<br><br>CONCLUSIONS: Binocular solar maculopathy can present asymmetrically and recover asymmetrically as well. The dominant eye suffered more obvious damage and poorer anatomical recovery than the nondominant eye.},
}
@article {pmid36950301,
year = {2023},
author = {Bousquet, E and Chenevier-Gobeaux, C and Jaworski, T and Torres-Villaros, H and Zola, M and Mantel, I and Kowalczuk, L and Matet, A and Daruich, A and Zhao, M and Yzer, S and Behar-Cohen, F},
title = {High Levels of C-Reactive Protein with Low Levels of Pentraxin 3 as Biomarkers for Central Serous Chorioretinopathy.},
journal = {Ophthalmology science},
volume = {3},
number = {3},
pages = {100278},
pmid = {36950301},
issn = {2666-9145},
abstract = {PURPOSE: To investigate the association between the 2 acute phase proteins, C-reactive protein (CRP) and pentraxin 3 (PTX3) with central serous chorioretinopathy (CSCR), as PTX3 is a glucocorticoid-induced protein.<br><br>DESIGN: Cross-sectional multicenter study.<br><br>PARTICIPANTS: Patients with CSCR compared with age- and sex-matched healthy participants.<br><br>METHODS: Patients with CSCR from 3 centers in Europe were included in the study. The clinical form of CSCR was recorded. Blood samples from patients with CSCR and healthy participants were sampled, and high-sensitivity CRP and PTX3 levels were measured in the serum.<br><br>MAIN OUTCOME MEASURES: C-reactive protein and PTX3 serum level comparison between patients with CSCR with age- and sex-matched healthy participants.<br><br>RESULTS: Although CRP levels were higher in patients with CSCR (n&#xa0;= 216) than in age- and sex-matched controls (n&#xa0;= 130) (2.2 &#xb1; 3.2 mg/l vs. 1.5 mg/l &#xb1; 1.4, respectively, P&#xa0;= 0.037), PTX3 levels were lower in patients with CSCR (10.5 &#xb1; 19.9 pg/ml vs. 87.4 &#xb1; 73.2 pg/ml, respectively, P < 0.001). There was no significant difference in CRP or PTX3 levels between patients with acute/recurrent and chronic CSCR.<br><br>CONCLUSIONS: In patients with CSCR, high CRP and low PTX3 levels suggest a form of low-grade systemic inflammation together with a lack of glucocorticoid pathway activation, raising new hypotheses on the pathophysiology of CSCR.<br><br>FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid36950236,
year = {2023},
author = {Lu, J and Cheng, Y and Li, J and Liu, Z and Shen, M and Zhang, Q and Liu, J and Herrera, G and Hiya, FE and Morin, R and Joseph, J and Gregori, G and Rosenfeld, PJ and Wang, RK},
title = {Automated segmentation and quantification of calcified drusen in 3D swept source OCT imaging.},
journal = {Biomedical optics express},
volume = {14},
number = {3},
pages = {1292-1306},
pmid = {36950236},
issn = {2156-7085},
abstract = {Qualitative and quantitative assessments of calcified drusen are clinically important for determining the risk of disease progression in age-related macular degeneration (AMD). This paper reports the development of an automated algorithm to segment and quantify calcified drusen on swept-source optical coherence tomography (SS-OCT) images. The algorithm leverages the higher scattering property of calcified drusen compared with soft drusen. Calcified drusen have a higher optical attenuation coefficient (OAC), which results in a choroidal hypotransmission defect (hypoTD) below the calcified drusen. We show that it is possible to automatically segment calcified drusen from 3D SS-OCT scans by combining the OAC within drusen and the hypoTDs under drusen. We also propose a correction method for the segmentation of the retina pigment epithelium (RPE) overlying calcified drusen by automatically correcting the RPE by an amount of the OAC peak width along each A-line, leading to more accurate segmentation and quantification of drusen in general, and the calcified drusen in particular. A total of 29 eyes with nonexudative AMD and calcified drusen imaged with SS-OCT using the 6 × 6 mm[2] scanning pattern were used in this study to test the performance of the proposed automated method. We demonstrated that the method achieved good agreement with the human expert graders in identifying the area of calcified drusen (Dice similarity coefficient: 68.27 ± 11.09%, correlation coefficient of the area measurements: r = 0.9422, the mean bias of the area measurements = 0.04781 mm[2]).},
}
@article {pmid36947606,
year = {2023},
author = {Bayless, KJ},
title = {Direct Involvement of CD8[+] T Cells in Retinal Angiogenesis.},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
volume = {43},
number = {4},
pages = {537-539},
doi = {10.1161/ATVBAHA.123.319101},
pmid = {36947606},
issn = {1524-4636},
mesh = {Humans ; CD8-Positive T-Lymphocytes ; Retina ; *Macular Degeneration ; *Diabetic Retinopathy ; Angiogenesis Inhibitors ; },
}
@article {pmid36946914,
year = {2023},
author = {Lee, SY and Tseng, VL and Kitayama, K and Avallone, TJ and Yu, F and Pan, D and Caprioli, J and Coleman, AL},
title = {Associations Between Niacin Intake and Glaucoma in the National Health and Nutrition Examination Survey.},
journal = {Journal of glaucoma},
volume = {32},
number = {6},
pages = {443-450},
doi = {10.1097/IJG.0000000000002216},
pmid = {36946914},
issn = {1536-481X},
mesh = {Adult ; Humans ; Female ; Nutrition Surveys ; *Niacin ; Cross-Sectional Studies ; Intraocular Pressure ; *Glaucoma/diagnosis/epidemiology/prevention &amp; control ; },
abstract = {PRCIS: This study examined the association between dietary niacin intake and glaucoma in the 2005-2008 National Health and Nutrition Examination Survey (NHANES). Increased niacin intake was associated with lower odds of glaucoma overall and among women.<br><br>PURPOSE: To examine the association between dietary niacin intake and glaucoma in the 2005-2008 NHANES.<br><br>MATERIALS AND METHODS: This cross-sectional study included adult participants of the 2005-2008 NHANES. The exposure was dietary niacin intake, which was examined as a continuous and categorical variable. The outcome was glaucoma as defined by regraded disc images. Covariates included age, sex, race/ethnicity, education level, income, body mass index, smoking status, alcohol use, cardiovascular disease, diabetes mellitus, daily energy intake, vitamin B2 and B6 consumption, and macular degeneration. Adjusting for all covariates, logistic regression was performed to examine the association between niacin intake and glaucoma in the overall population and stratified by sex.<br><br>RESULTS: The weighted population included 5371 individuals (109,734,124 weighted), of whom 55 (1.0%) had glaucoma. Each 1 mg increase in niacin intake was associated with a 6% decreased odds of glaucoma odds [adjusted odds ratio (aOR) = 0.94, 95% CI = 0.90, 0.98]. Among women, increased niacin intake was associated with decreased odds of glaucoma both with niacin as a continuous (aOR = 0.89, 95% CI = 0.80, 0.99 per 1 mg increase in niacin intake) and binary variable (aOR = 0.35, 95% CI = 0.14, 0.90 for higher vs lower niacin intake).<br><br>CONCLUSIONS: In the 2005-2008 NHANES population, higher levels of niacin intake were associated with decreased odds of glaucoma overall and in women. Further studies are needed to examine the potential protective effects of niacin on glaucoma risk.},
}
@article {pmid36945110,
year = {2023},
author = {Wang, Y and Chen, Y and Liang, J and Jiang, M and Zhang, T and Wan, X and Wu, J and Li, X and Chen, J and Sun, J and Hu, Y and Huang, P and Feng, J and Liu, T and Sun, X},
title = {METTL3-mediated m6A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition.},
journal = {Journal of molecular cell biology},
volume = {15},
number = {3},
pages = {},
pmid = {36945110},
issn = {1759-4685},
mesh = {Animals ; Humans ; Mice ; *Epithelial-Mesenchymal Transition/genetics ; Fibrosis ; *Methyltransferases/genetics ; RNA, Messenger/genetics ; Transcription Factors ; HMGA2 Protein ; },
abstract = {Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration (nAMD). Myofibroblasts originated from retinal pigment epithelial (RPE) cells through epithelial-mesenchymal transition (EMT) contribute to the fibrosis formation. N6-Methyladenosine (m6A) modification has been implicated in the EMT process and multiple fibrotic diseases. The role of m6A modification in EMT-related subretinal fibrosis has not yet been elucidated. In this study, we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization, METTL3 was upregulated in RPE cells. Through m6A epitranscriptomic microarray and further verification, high-mobility group AT-hook 2 (HMGA2) was identified as the key downstream target of METTL3, subsequently activating potent EMT-inducing transcription factor SNAIL. Finally, by subretinal injections of adeno-associated virus vectors, we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo. In conclusion, our present research identified an epigenetic mechanism of METTL3-m6A-HMGA2 in subretinal fibrosis and EMT of RPE cells, providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.},
}
@article {pmid36944806,
year = {2023},
author = {Yuan, Y and Kong, W and Liu, XM and Shi, GH},
title = {Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model.},
journal = {Current medical science},
volume = {43},
number = {2},
pages = {384-392},
pmid = {36944806},
issn = {2523-899X},
mesh = {Mice ; Animals ; *beta Catenin/genetics/metabolism ; Retinal Pigment Epithelium ; *Macular Degeneration/genetics/therapy ; Cell Proliferation/genetics ; Genetic Therapy ; },
abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a degenerative retinal disease. The degeneration or death of retinal pigment epithelium (RPE) cells is implicated in the pathogenesis of AMD. This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus (AAV) vector encoding β-catenin to treat AMD in a mouse model.<br><br>METHODS: Mice were intravitreally injected with AAV2/8-Y733F-VMD2-&#x3b2;-catenin for 2 or 4 weeks, and &#x3b2;-catenin expression was measured using immunofluorescence staining, real-time quantitative reverse transcription polymerase chain reaction (PCR), and Western blotting. The function of &#x3b2;-catenin was determined using retinal flat mounts and laser-induced damage models. Finally, the safety of AAV2/8-Y733F-VMD2-&#x3b2;-catenin was evaluated by multiple intravitreal injections.<br><br>RESULTS: AAV2/8-Y733F-VMD2-&#x3b2;-catenin induced the expression of &#x3b2;-catenin in RPE cells. It activated the proliferation of RPE cells and increased cyclin D1 expression. It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells. Furthermore, it could induce apoptosis of RPE cells by increasing the expression of Trp53, Bax and caspase3 while decreasing the expression of Bcl-2.<br><br>CONCLUSION: AAV2/8-Y733F-VMD2-&#x3b2;-catenin increased &#x3b2;-catenin expression in RPE cells, activated RPE cell proliferation, and helped mice heal from laser-induced eye injury. Furthermore, it could induce the apoptosis of RPE cells. Therefore, it may be a safe approach for AMD treatment.},
}
@article {pmid36944313,
year = {2023},
author = {Tarita-Nistor, L and Sverdlichenko, I and Mandelcorn, MS},
title = {What Is a Preferred Retinal Locus?.},
journal = {Annual review of vision science},
volume = {9},
number = {},
pages = {201-220},
doi = {10.1146/annurev-vision-111022-123909},
pmid = {36944313},
issn = {2374-4650},
mesh = {Humans ; *Retina ; *Retinal Diseases ; },
abstract = {This review examines the concept of the preferred retinal locus (PRL) in patients with macular diseases. Considering monocular and binocular viewing, we (a) explain how to identify the PRL and discuss the pitfalls associated with its measurement, (b) review the current hypotheses for PRL development, (c) assess whether the PRL is the new reference point of the ocular motor system, and discuss (d) the functional and (e) the clinical implications of the PRL. We conclude that the current definition of the PRL is probably incomplete and should incorporate the need to evaluate the PRL in the framework of binocular viewing. We emphasize the need for more research.},
}
@article {pmid36944176,
year = {2023},
author = {Berlin, A and Messinger, J and Ferrara, D and Freund, KB and Curcio, CA},
title = {OPTICAL COHERENCE TOMOGRAPHY FEATURES RELEVANT TO NEOVASCULAR AGE-RELATED MACULAR DEGENERATION MANAGEMENT AND NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION PROGRESSION: CLINICOPATHOLOGIC CORRELATION.},
journal = {Retinal cases &amp; brief reports},
volume = {17},
number = {4S},
pages = {S41-S46},
doi = {10.1097/ICB.0000000000001356},
pmid = {36944176},
issn = {1937-1578},
mesh = {Female ; Humans ; Child, Preschool ; Tomography, Optical Coherence/methods ; Retrospective Studies ; *Macular Degeneration/diagnosis/complications ; Choroid ; Atrophy ; Fluorescein Angiography/methods ; *Choroidal Neovascularization/diagnosis/drug therapy/complications ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; },
abstract = {PURPOSE: Clinicopathologic correlation of two optical coherence tomography (OCT) features in neovascular age-related macular degeneration.<br><br>METHODS: Case report, clinicopathologic correlation.<br><br>RESULTS: A patient in her 90s was diagnosed with Type 3 macular neovascularization secondary to age-related macular degeneration in the index right eye and underwent intravitreal antivascular endothelial growth factor treatment for 5 years. A double-layer sign on in vivo OCT was correlated to calcified drusen on histology. Furthermore, hyperfluorescence on fluorescein angiography corresponded on histology to choroidal hypertransmission on OCT and retinal pigment epithelium atrophy above calcified drusen.<br><br>CONCLUSION: A double-layer sign on OCT can represent nonneovascular subretinal pigment epithelium material including wide and flat calcific nodules. Furthermore, hyperfluorescence on FA, among different origins, can be due to a window defect corresponding to retinal pigment epithelium atrophy, which can be confirmed with OCT. Clinicopathological correlation using high-resolution histology can demonstrate the fine details available to clinical decision making through currently available in vivo OCT imaging.},
}
@article {pmid36944073,
year = {2023},
author = {Alsoudi, AF and Loya, A and Abouodah, H and Koo, E and Rahimy, E},
title = {An Evaluation of Popular Online Eye Health Products on Amazon Marketplace.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {3},
pages = {147-152},
doi = {10.3928/23258160-20230221-03},
pmid = {36944073},
issn = {2325-8179},
mesh = {Humans ; *Vitamins ; Dietary Supplements ; *Macular Degeneration ; Vitamin A ; Vitamin K ; },
abstract = {BACKGROUND AND OBJECTIVE: To investigate popular eye health supplements available on Amazon Marketplace to increase awareness about their efficacy, safety, and the validity of their purported benefits.<br><br>MATERIALS AND METHODS: An observational quantitative and qualitative analysis of the top 100 eye health products was performed in March 2019. To determine the popular online eye health products on Amazon Marketplace, eight keywords were used for the search: "Eye Health," "Eye Health Supplements," "Eye Health Vitamins," "Retina Vitamins," "Macular Degeneration," "Macular Degeneration Vitamins," "Macular Health," and "Vision Health." The active ingredients, cost, and customer rating were all recorded.<br><br>RESULTS: No statistically significant association was found between product type and price of the product, number of supplements, average rating, number of customer reviews, or number of verified customer reviews. The average daily cost of the eye health supplements was $0.72 &#xb1; $0.55 (range, $0.05 to $2.67).<br><br>CONCLUSION: This study evaluated popular eye health supplements publicly available on Amazon Marketplace. The findings of this study help both patients and physicians better understand the safety and efficacy of these products so they may make more informed choices when supporting their eye health with commercially available supplements. [Ophthalmic Surg Lasers Imaging Retina 2023; 54(3):147-152.].},
}
@article {pmid36943473,
year = {2023},
author = {DeBoer, CMT and Agrawal, R and Rahimy, E},
title = {Novel oral medications for retinal disease: an update on clinical development.},
journal = {Current opinion in ophthalmology},
volume = {34},
number = {3},
pages = {203-210},
pmid = {36943473},
issn = {1531-7021},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Diabetic Retinopathy/drug therapy ; Stargardt Disease ; *Retinal Diseases/drug therapy ; *Macular Degeneration/drug therapy ; Injections ; Pharmaceutical Preparations ; Intravitreal Injections ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {PURPOSE OF REVIEW: Intravitreal and periocular injections for retinal disease provide a targeted delivery of medication to the eye. However, given risks of injections, including endophthalmitis, pain and treatment burden for both patients and retina specialists, there has been significant interest and effort in developing oral medications for the management of retinal disease. This article provides clinical and preclinical details of new oral medications in the pipeline for management of retinal disease.<br><br>RECENT FINDINGS: Several new oral medications show clinical and preclinical promise for the management of retinal disease, including macular degeneration, diabetic retinopathy and Stargardt disease.<br><br>SUMMARY: Oral medications provide promise for treating retinal disease, possibly increasing compliance, and reducing side effects of intravitreal or periocular injections. However, difficulties in this approach include systemic side effects and efficacy targeting the eye. There are multiple medications that are currently under investigation with the potential to act as stand-alone treatment or as an adjunct treatment for management of retinal diseases such as diabetic retinopathy, macular degeneration and Stargardt disease.},
}
@article {pmid36943458,
year = {2023},
author = {Clevenger, L and Rachitskaya, A},
title = {Identifying geographic atrophy.},
journal = {Current opinion in ophthalmology},
volume = {34},
number = {3},
pages = {195-202},
doi = {10.1097/ICU.0000000000000952},
pmid = {36943458},
issn = {1531-7021},
mesh = {Humans ; *Geographic Atrophy/diagnosis/etiology ; Disease Progression ; Fluorescein Angiography ; *Macular Degeneration/diagnosis ; Prognosis ; Tomography, Optical Coherence/methods ; Atrophy/complications ; },
abstract = {PURPOSE OF REVIEW: Age-related macular degeneration (AMD) is one of the leading causes of blindness and can progress to geographic atrophy (GA) in late stages of disease. This review article highlights recent literature which assists in the accurate and timely identification of GA, and monitoring of GA progression.<br><br>RECENT FINDINGS: Technology for diagnosing and monitoring GA has made significant advances in recent years, particularly regarding the use of optical coherence tomography (OCT). Identification of imaging features which may herald the development of GA or its progression is critical. Deep learning applications for OCT in AMD have shown promising growth over the past several years, but more prospective studies are needed to demonstrate generalizability and clinical utility.<br><br>SUMMARY: Identification of GA and of risk factors for GA development or progression is essential when counseling AMD patients and discussing prognosis. With new therapies on the horizon for the treatment of GA, identification of risk factors for the development and progression of GA will become critical in determining the patients who would be appropriate candidates for new targeted therapies.},
}
@article {pmid36939720,
year = {2023},
author = {Yoon, CK and Kim, YA and Park, UC and Kwon, SH and Lee, Y and Yoo, HJ and Seo, JH and Yu, HG},
title = {Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {3},
pages = {28},
pmid = {36939720},
issn = {1552-5783},
mesh = {Humans ; *Amides ; *Carnitine ; *Macular Degeneration ; Niacinamide ; Succinates ; *Vitreous Body/metabolism ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics.<br><br>METHODS: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0.<br><br>RESULTS: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment.<br><br>CONCLUSIONS: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.},
}
@article {pmid36939084,
year = {2023},
author = {Keenan, TDL and Agrón, E and Chew, EY and , },
title = {Dietary nutrient intake and cognitive function in the Age-Related Eye Disease Studies 1 and 2.},
journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association},
volume = {19},
number = {10},
pages = {4311-4324},
pmid = {36939084},
issn = {1552-5279},
support = {Z99 EY999999/ImNIH/Intramural NIH HHS/United States ; ZIA EY000485/ImNIH/Intramural NIH HHS/United States ; /NH/NIH HHS/United States ; N01EY50007/EY/NEI NIH HHS/United States ; N01 EY002127/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Lutein ; Zeaxanthins ; Vitamins ; Dietary Supplements ; *Macular Degeneration/prevention &amp; control ; Eating ; Cognition ; },
abstract = {INTRODUCTION: The objective was to analyze associations between dietary intake of multiple nutrients and altered cognitive function and/or decline.<br><br>METHODS: Observational analyses of participants (n&#xa0;=&#xa0;6334) in two randomized trials of nutritional supplements for age-related macular degeneration: Age-Related Eye Disease Study (AREDS) and AREDS2.<br><br>RESULTS: In AREDS, for 4 of 38 nutrients examined, higher intake quintiles were significantly associated with decreased risk of cognitive impairment on the Modified Mini-Mental State test (<80): &#x3b2;-carotene, copper, docosahexaenoic acid, and insoluble fiber. In AREDS2, for 13 of 44 nutrients, higher intake quintiles were associated with decreased risk on the Telephone Interview Cognitive Status-Modified (<30). Rate of cognitive decline over up to 10 years was not significantly different with higher intake of any nutrient.<br><br>DISCUSSION: Higher dietary intake of multiple nutrients, including specific vitamins, minerals, carotenoids, fatty acids, and fiber, was associated with lower risk of cognitive impairment but not slower decline in cognitive function.},
}
@article {pmid36938233,
year = {2023},
author = {Mody, S and Joshi, A},
title = {Age-Related Macular Degeneration and Its Association With Neurodegenerative Disorders.},
journal = {Cureus},
volume = {15},
number = {2},
pages = {e34920},
pmid = {36938233},
issn = {2168-8184},
abstract = {Age-related macular degeneration (AMD) is a highly prevalent macular condition that primarily affects the older population. It is the primary cause of blindness amongst the elderly population. It is an inflammatory disease that characteristically shows choroidal neovascularization and geographic atrophy. The exact pathomechanism of developing AMD is not known. However, certain factors such as increased age, smoking, genetic factors and certain environmental factors are usually associated with the development of the disease. AMD also involves oxidative stress-mediated destruction of retinal pigment epithelial cells and, consequently, that of retinal photoreceptors. Alzheimer's disease (AD) is a degenerative disorder involving the nervous system that usually affects people aged 65 and over. Both AMD and AD are age-related, degenerative conditions that have several similarities and share many of the same risk factors such as vascular conditions like arteriosclerosis, high blood pressure and obesity. It is believed that the early emergence of the clinical manifestations of AMD and AD may also be significantly influenced by oxidative stress and genetic polymorphism in complement factor H. A common pathogenic pathway between AD and AMD is quite likely. Amyloid-β is an aberrant protein that accumulates within the brains of Alzheimer's patients and appears as plaques on magnetic resonance imaging (MRI). These plaques are a pathognomonic sign of Alzheimer's disease. Similar to this, amyloid-β deposits are reported to build up beneath the retina of AMD patients, which appear as tiny clusters of protein-lipid substances known as drusen. It has also been found that individuals suffering from AMD exhibit an increased chance of developing AD than those with no AMD.},
}
@article {pmid36937463,
year = {2023},
author = {Hussein, ZR and Omar, SK and Alkazraji, RAM and Alsamarrai, AN and Alrubaye, HS and Al-Hussaniy, HA},
title = {Efficacy of Aflibercept as initial treatment for neovascular age-related macular degeneration in an Iraqi patient sample.},
journal = {Journal of medicine and life},
volume = {16},
number = {2},
pages = {235-243},
pmid = {36937463},
issn = {1844-3117},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Treatment Outcome ; Follow-Up Studies ; Prospective Studies ; Iraq ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/diagnostic imaging/drug therapy ; Tomography, Optical Coherence ; Intravitreal Injections ; },
abstract = {Age-related macular degeneration (AMD) is a progressive degenerative eye disorder that primarily affects individuals over 50. It causes gradual loss of central vision and can lead to irreversible severe visual loss if left untreated. AMD is a leading cause of blindness in the developed world. This study aimed to investigate the effects of a loading dosage of intravitreal Aflibercept on functional and morphological responses in neovascular AMD, considering demographic characteristics and the link between AMD-related retinal symptoms at presentations. A prospective interventional study was conducted from November 2021 to September 2022 on a sample of Iraqi patients with neovascular AMD who had active choroidal neovascularization (CNV) lesions confirmed by OCT-A and received intravitreal Aflibercept 2mg injection as initial therapy (3 loading doses). Best-corrected visual acuity (BCVA) was used to measure functional responses, and central macular thickness (CMT) and maximum area of the retinal thickness (MART) (by SD-OCT) were used to measure morphological responses. The study included 48 patients (57 eyes) with active neovascular AMD. The mean difference of BCVA in log MAR (0.2 ± 0.7) significantly improved from 1.3±0.7 at baseline to 1.1±0.8 after loading Aflibercept (P=0.034). The mean difference in CMT 113.6 ± 125.9 was statistically significant (P<0.0001). Also, the mean change in MART significantly decreased from 444.2 ± 127.1 µm at baseline to 348.7±74.5 µm (p < 0.0001) after loading Aflibercept. This study demonstrated that Aflibercept is a functionally and anatomically successful treatment for neovascular AMD.},
}
@article {pmid36937188,
year = {2023},
author = {Goebel, CP and Song, YS and Zaitoun, IS and Wang, S and Potter, HAD and Sorenson, CM and Sheibani, N},
title = {Adenosine Receptors Expression in Human Retina and Choroid with Age-related Macular Degeneration.},
journal = {Journal of ophthalmic &amp; vision research},
volume = {18},
number = {1},
pages = {51-59},
pmid = {36937188},
issn = {2008-2010},
support = {R01 EY032543/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Adenosine signaling modulates ocular inflammatory processes, and its antagonism mitigates neovascularization in both newborns and preclinical models of ocular neovascularization including age-related macular degeneration (AMD). The adenosine receptor expression patterns have not been well characterized in the human retina and choroid.<br><br>METHODS: Here we examined the expression of adenosine receptor subtypes within the retina and choroid of human donor eyes with and without AMD. Antibodies specifically targeting adenosine receptor subtypes A1, A2A, A2B, and A3 were used to assess their expression patterns. Quantitative real-time PCR analysis was used to confirm gene expression of these receptors within the normal human retina and choroid.<br><br>RESULTS: We found that all four receptor subtypes were expressed in several layers of the retina, and within the retinal pigment epithelium and choroid. The expression of A1 receptors was more prominent in the inner and outer plexiform layers, where microglia normally reside, and supported by RNA expression in the retina. A2A and A2B showed similar expression patterns with prominent expression in the vasculature and retinal pigment epithelium. No dramatic differences in expression of these receptors were observed in eyes from patients with dry or wet AMD compared to control, with the exception A3 receptors. Eyes with dry AMD lost expression of A3 in the photoreceptor outer segments compared with eyes from control or wet AMD.<br><br>CONCLUSION: The ocular presence of adenosine receptors is consistent with their proposed role in modulation of inflammation in both the retina and choroid, and their potential targeting for AMD treatment.},
}
@article {pmid36937046,
year = {2023},
author = {Aggio-Bruce, R and Schumann, U and Cioanca, AV and Chen, FK and McLenachan, S and Heath Jeffery, RC and Das, S and Natoli, R},
title = {Serum miRNA modulations indicate changes in retinal morphology.},
journal = {Frontiers in molecular neuroscience},
volume = {16},
number = {},
pages = {1130249},
pmid = {36937046},
issn = {1662-5099},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.<br><br>METHODS: Serum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5&#x2009;days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray&#x2122;, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.<br><br>RESULTS: Differential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.<br><br>CONCLUSION: In conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.},
}
@article {pmid36936905,
year = {2023},
author = {Biasella, F and Plössl, K and Baird, PN and Weber, BHF},
title = {The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1147037},
pmid = {36936905},
issn = {1664-3224},
mesh = {*Optic Disk Drusen/pathology/congenital ; Inflammation/pathology ; Retina/pathology ; Humans ; *Macular Degeneration/genetics ; },
abstract = {Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their phenotypic and genotypic characteristics. Therefore, overlaps in clinical features often complicate or even impede their correct clinical diagnosis. Deciphering the molecular basis of retinal diseases has not only aided in their disease classification but also helped in our understanding of how different molecular pathologies may share common pathomechanisms. In particular, these relate to dysregulation of two key processes that contribute to cellular integrity, namely extracellular matrix (ECM) homeostasis and inflammation. Pathological changes in the ECM of Bruch's membrane have been described in both monogenic IRDs, such as Sorsby fundus dystrophy (SFD) and Doyne honeycomb retinal dystrophy (DHRD), as well as in the genetically complex age-related macular degeneration (AMD) or diabetic retinopathy (DR). Additionally, complement system dysfunction and distorted immune regulation may also represent a common connection between some IRDs and complex retinal degenerations. Through highlighting such overlaps in molecular pathology, this review aims to illuminate how inflammatory processes and ECM homeostasis are linked in the healthy retina and how their interplay may be disturbed in aging as well as in disease.},
}
@article {pmid36936225,
year = {2023},
author = {Li, Z and Guo, X and Zhang, J and Liu, X and Chang, R and He, M},
title = {Using deep leaning models to detect ophthalmic diseases: A comparative study.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1115032},
pmid = {36936225},
issn = {2296-858X},
abstract = {PURPOSE: The aim of this study was to prospectively quantify the level of agreement among the deep learning system, non-physician graders, and general ophthalmologists with different levels of clinical experience in detecting referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy.<br><br>METHODS: Deep learning systems for diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy classification, with accuracy proven through internal and external validation, were established using 210,473 fundus photographs. Five trained non-physician graders and 47 general ophthalmologists from China were chosen randomly and included in the analysis. A test set of 300 fundus photographs were randomly identified from an independent dataset of 42,388 gradable images. The grading outcomes of five retinal and five glaucoma specialists were used as the reference standard that was considered achieved when &#x2265;50% of gradings were consistent among the included specialists. The area under receiver operator characteristic curve of different groups in relation to the reference standard was used to compare agreement for referable diabetic retinopathy, age-related macular degeneration, and glaucomatous optic neuropathy.<br><br>RESULTS: The test set included 45 images (15.0%) with referable diabetic retinopathy, 46 (15.3%) with age-related macular degeneration, 46 (15.3%) with glaucomatous optic neuropathy, and 163 (55.4%) without these diseases. The area under receiver operator characteristic curve for non-physician graders, ophthalmologists with 3-5&#x2009;years of clinical practice, ophthalmologists with 5-10&#x2009;years of clinical practice, ophthalmologists with >10&#x2009;years of clinical practice, and the deep learning system for referable diabetic retinopathy were 0.984, 0.964, 0.965, 0.954, and 0.990 (p&#x2009;=&#x2009;0.415), respectively. The results for referable age-related macular degeneration were 0.912, 0.933, 0.946, 0.958, and 0.945, respectively, (p&#x2009;=&#x2009;0.145), and 0.675, 0.862, 0.894, 0.976, and 0.994 for referable glaucomatous optic neuropathy, respectively (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: The findings of this study suggest that the accuracy of this deep learning system is comparable to that of trained non-physician graders and general ophthalmologists for referable diabetic retinopathy and age-related macular degeneration, but the deep learning system performance is better than that of trained non-physician graders for the detection of referable glaucomatous optic neuropathy.},
}
@article {pmid36936101,
year = {2023},
author = {Guérios, EE and Chamié, F},
title = {Percutaneous left atrial appendage closure: beyond the classic indications.},
journal = {AsiaIntervention},
volume = {9},
number = {1},
pages = {70-77},
pmid = {36936101},
issn = {2491-0929},
abstract = {Percutaneous left atrial appendage closure (LAAC) has proven to be an effective alternative to oral anticoagulation (OAC) for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). International guidelines traditionally recommend LAAC for NVAF patients at high thromboembolic risk and contraindication to or at high risk for OAC. However, there are many other clinical situations in which this procedure may also be beneficial. This paper discusses the potential role of LAAC in specific haemorrhagic diseases (cerebral amyloid angiopathy, age-related macular degeneration, hereditary haemorrhagic telangiectasia, and Moyamoya disease), after left atrial appendage (LAA) electrical isolation, in cases of persistent thrombus inside the LAA, in end-stage renal disease and in special groups of patients for whom low compliance and persistence to OAC may be anticipated.},
}
@article {pmid36935183,
year = {2023},
author = {Lin, Y and Gao, L and Jiang, W},
title = {Analysis of the epidemiological burden of age-related macular degeneration in China based on the data of global burden of disease.},
journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences},
volume = {48},
number = {1},
pages = {106-113},
pmid = {36935183},
issn = {1672-7347},
support = {2020JJ4789//the Natural Science Foundation of Hunan Province/ ; 202307027224//the Project of Health Commission of Hunan Province/ ; kq2208347//the Natural Science Foundation of Changsha/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Global Burden of Disease ; Quality-Adjusted Life Years ; Prevalence ; *Macular Degeneration/epidemiology ; China/epidemiology ; },
abstract = {OBJECTIVES: Age-related macular degeneration (AMD) is one of the 3 major eye diseases recognized by WHO to prevent blindness, and which is the main cause of irreversible visual impairment in the elderly. This study aims to analyze the disease epidemiological burden, and provide a theoretical foundation for the prevention and control of AMD in China based on the data in global burden of disease (GBD) 2019.<br><br>METHODS: The prevalent cases/prevalence, disability-adjusted life year (DALYs)/DALY rate of AMD and socio-demographic index (SDI) for global and China were searched from the GBD 2019 database to analyze the epidemiological trend, age-period-gender trend of AMD in China from 1990 to 2019, and to evaluate the relations between the prevalence and SDI.<br><br>RESULTS: In 2019, the prevalence of AMD in China was at a high level in the world, and the number of prevalent cases were 1.93 times of that in 1990. The prevalence and DALY rates continued to rise. The age trend of AMD in China was high at the middle of the age stages and low at the two ends, and which was higher in the female than in the male. With the increase of SDI, the prevalence of AMD was increased linearly.<br><br>CONCLUSIONS: The disease burden of AMD in China is increased significantly and is positively correlated with the social development from 1990 to 2019. It is of great significance to study the relationship between epidemilolgical data of AMD and social development level for diagnosis treatment and policy of AMD.},
}
@article {pmid36934857,
year = {2023},
author = {Ren, JS and Bai, W and Ding, JJ and Zhao, Y and Wang, SY and Chen, X and Jiang, Q},
title = {The role of PIWIL4 and piRNAs in the development of choroidal neovascularization.},
journal = {Genomics},
volume = {115},
number = {3},
pages = {110615},
doi = {10.1016/j.ygeno.2023.110615},
pmid = {36934857},
issn = {1089-8646},
mesh = {Humans ; Aged ; Animals ; Mice ; *Piwi-Interacting RNA ; Vascular Endothelial Growth Factor A/metabolism ; *Choroidal Neovascularization/drug therapy/etiology/pathology ; Intravitreal Injections ; Disease Models, Animal ; Mice, Inbred C57BL ; Argonaute Proteins/metabolism ; },
abstract = {Wet age-related macular degeneration (wAMD) is the leading cause of blindness among the elderly in industrialized nations. Anti-vascular epidermal growth factor (VEGF) therapy via intravitreal injection is the most effective clinical treatment for wAMD due to high concentrations of VEGF that promote choroidal neovascularization. While PIWI proteins participate in various biological processes, their function in AMD remains unclear. In this study, we discovered that PIWIL4 expression is elevated in a laser-induced choroidal neovascularization (CNV) model and that it regulates angiogenesis in vitro and in vivo. Differentially expressed piwi-interacting RNAs (piRNAs) were identified in a CNV model and were shown to potentially regulate angiogenesis via bioinformatics analysis. PIWIL4 knockdown inhibits VEGF secretion and VEGFR2 phosphorylation. Overall, PIWIL4 may serve as a novel target to block pathological choroidal neovascularization, and the study of the PIWI-piRNAs pathway in wAMD highlights its broad function in somatic cells.},
}
@article {pmid36933392,
year = {2023},
author = {Ma, X and Chen, H and Jian, S and He, J and Liu, Y and Han, S and Chang, L and Li, P and Chen, YA and Liu, X and Hu, X and Chen, Y and Hou, L},
title = {DAPL1 deficiency in mice impairs antioxidant defenses in the RPE and leads to retinal degeneration with AMD-like features.},
journal = {Redox biology},
volume = {62},
number = {},
pages = {102675},
pmid = {36933392},
issn = {2213-2317},
mesh = {Animals ; Mice ; Antioxidants/metabolism ; Cell Line ; *Macular Degeneration/genetics/pathology ; Membrane Proteins/metabolism ; Oxidative Stress ; *Retinal Degeneration/metabolism ; Retinal Pigment Epithelium/metabolism ; Transcription Factors/metabolism ; },
abstract = {The decreased antioxidant capacity in the retinal pigment epithelium (RPE) is the hallmark of retinal degenerative diseases including age-related macular degeneration (AMD). Nevertheless, the exact regulatory mechanisms underlying the pathogenesis of retinal degenerations remain largely unknown. Here we show in mice that deficiencies in Dapl1, a susceptibility gene for human AMD, impair the antioxidant capacity of the RPE and lead to age-related retinal degeneration in the 18-month-old mice homozygous for a partial deletion of Dapl1. Dapl1-deficiency is associated with a reduction of the RPE's antioxidant capacity, and experimental re-expression of Dapl1 reverses this reduction and protects the retina from oxidative damage. Mechanistically, DAPL1 directly binds the transcription factor E2F4 and inhibits the expression of MYC, leading to upregulation of the transcription factor MITF and its targets NRF2 and PGC1α, both of which regulate the RPE's antioxidant function. When MITF is experimentally overexpressed in the RPE of DAPL1 deficient mice, antioxidation is restored and retinas are protected from degeneration. These findings suggest that the DAPL1-MITF axis functions as a novel regulator of the antioxidant defense system of the RPE and may play a critical role in the pathogenesis of age-related retinal degenerative diseases.},
}
@article {pmid36933125,
year = {2023},
author = {Iovino, C and Iodice, CM and Pisani, D and Rosolia, A and Testa, F and Giannaccare, G and Chhablani, J and Simonelli, F},
title = {Yellow Subthreshold Micropulse Laser in Retinal Diseases: An In-Depth Analysis and Review of the Literature.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {3},
pages = {1479-1500},
pmid = {36933125},
issn = {2193-8245},
abstract = {Yellow subthreshold micropulse laser (YSML) is a retinal laser capable of inducing a biologic response without causing thermal damage to the targeted tissue. The 577-nm YSML is delivered to the retina abiding by different protocols in which wavelength, power, duration, spot size and number of spots can be properly set to achieve the most effective and safe treatment response in various chorioretinal disorders. The ultrashort trains of power modulate the activation of the retinal pigment epithelium cells and intraretinal cells, such as Müller cells, causing no visible retinal scars. Subthreshold energy delivered by YSML stimulates the production of the heat-shock proteins, highly conserved molecules that protect cells against any sort of stress by blocking apoptotic and inflammatory pathways that cause cell damage. YSML treatment allows resorption of the subretinal fluid in central serous chorioretinopathy and intraretinal fluid in various conditions including diabetic macular edema, postoperative cystoid macular edema and other miscellaneous conditions. YSML also seems to modulate the development and progression of reticular pseudodrusen in dry age-related macular degeneration. The aim of this review is to discuss and summarize the safety and efficacy of YSML treatment in retinal diseases.},
}
@article {pmid36932356,
year = {2023},
author = {Lukacs, R and Schneider, M and Nagy, ZZ and Sandor, GL and Kaan, K and Asztalos, A and Enyedi, L and Pek, G and Barcsay, G and Szabo, A and Borbandy, A and Kovacs, I and Resch, MD and Papp, A},
title = {Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {110},
pmid = {36932356},
issn = {1471-2415},
mesh = {Humans ; *Ranibizumab/therapeutic use ; Angiogenesis Inhibitors ; Endothelial Growth Factors/therapeutic use ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD.<br><br>METHODS: Two clinical trial sites recruited their original subjects for a re-evaluation 7&#xa0;years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included.<br><br>RESULTS: Mean number of injections was 17.8&#x2009;&#xb1;&#x2009;3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7&#x2009;&#xb1;&#x2009;4.5 after the trial. At a mean follow-up time of 82&#x2009;&#xb1;&#x2009;5&#xa0;months best corrected visual acuity (BCVA) remained stable or improved (&#x2264;&#x2009;10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54&#x2009;&#xb1;&#x2009;13 letters at baseline, 65&#x2009;&#xb1;&#x2009;17 letters at the end of the intensive phase and 45&#x2009;&#xb1;&#x2009;25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p&#x2009;=&#x2009;0.88) and at the end of follow-up (p&#x2009;=&#x2009;0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22&#x2009;&#xb1;&#x2009;6.31 mm[2] with no statistically significant difference between groups (p&#x2009;=&#x2009;0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p&#x2009;<&#x2009;0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity.<br><br>CONCLUSION: Long-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy.<br><br>TRIAL REGISTRATIONS: VIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008. Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.},
}
@article {pmid36931431,
year = {2023},
author = {Lee, H and Han, KD and Shin, J},
title = {Association between glycemic status and age-related macular degeneration: A nationwide population-based cohort study.},
journal = {Diabetes &amp; metabolism},
volume = {49},
number = {3},
pages = {101442},
doi = {10.1016/j.diabet.2023.101442},
pmid = {36931431},
issn = {1878-1780},
mesh = {Adult ; Humans ; Aged ; Retrospective Studies ; Blood Glucose ; *Diabetes Mellitus, Type 2/complications/epidemiology ; Cohort Studies ; Risk Factors ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; },
abstract = {AIM: The risk of dry and wet age-related macular degeneration (AMD) based on fasting glucose levels and disease duration of type 2 diabetes was investigated.<br><br>METHODS: Using a health insurance claims database and the results of health examinations in South Korea, we conducted a retrospective, population-based cohort study of 2,103,604 adults &#x2265; 45 years of age who were AMD-free based on health checkups in 2009 and observed from January 1, 2011, to December 31, 2018. Glycemic status was classified into five groups: normal, impaired fasting glucose, new-onset diabetes (fasting glucose level &#x2265; 126&#xa0;mg/dl but no diabetes diagnosis or diabetes medication), diabetes diagnosis < 5 years, and diabetes &#x2265; 5 years. According to the presence and absence of choroidal neovascularization, AMD was classified as wet AMD and dry AMD, respectively. Adjusted hazard ratios (HRs) of AMD occurrence were estimated in each category.<br><br>RESULTS: For dry AMD (n&#xa0;=&#xa0;36,271, 1.72%), the HR was 1.192 (1.141-1.245) among subjects with diabetes < 5 years and 1.294 (1.242-1.349) among subjects with diabetes &#x2265; 5 years compared with subjects with normal glycemic status after adjusting for age, sex, body mass index, lifestyle, and medical history. For wet AMD (n&#xa0;=&#xa0;12,912, 0.61%), the HR was 1.103 (1.011-1.203) among subjects with new-onset diabetes, 1.252 (1.167-1.344) among subjects with diabetes < 5 years, and 1.506 (1.413-1.605) among subjects with diabetes &#x2265; 5 years. The HR of AMD was significantly increased among participants &#x2264; 65 years old and those who did not have hypertension.<br><br>CONCLUSIONS: The incidence of dry and wet AMD increased among diabetes patients compared to the normal glycemic status group. These risks increased when the duration of diabetes was 5 years or more. The risk of wet AMD was increased among new-onset diabetes patients. These results suggest that high blood glucose levels without treatment might induce the vision-threatening condition of wet AMD, emphasizing the importance of early blood glucose management.},
}
@article {pmid36930890,
year = {2023},
author = {Ricca, AM and Han, IC and Hoffmann, J and Stone, EM and Sohn, EH},
title = {MACULAR ATROPHY AND PHENOTYPIC VARIABILITY IN AUTOSOMAL DOMINANT STARGARDT-LIKE MACULAR DYSTROPHY DUE TO PROM1 MUTATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {7},
pages = {1165-1173},
pmid = {36930890},
issn = {1539-2864},
support = {P30 EY025580/EY/NEI NIH HHS/United States ; R01 EY026547/EY/NEI NIH HHS/United States ; },
mesh = {Female ; Male ; Humans ; *Geographic Atrophy ; Retrospective Studies ; *Macular Degeneration/diagnosis/genetics ; Mutation ; Atrophy ; Biological Variation, Population ; Tomography, Optical Coherence ; Fluorescein Angiography ; ATP-Binding Cassette Transporters/genetics ; AC133 Antigen/genetics ; },
abstract = {PURPOSE: To describe the phenotypic variability and rates of progression of atrophy in patients with PROM1 -associated macular dystrophy.<br><br>METHODS: Patients in this retrospective, longitudinal case series from a tertiary center had clinical examination and multimodal imaging performed. Areas of retinal pigment epithelium and ellipsoid zone loss over time by optical coherence tomography were calculated by two independent graders.<br><br>RESULTS: Fifteen patients from five kindreds with an Arg373Cys mutation in PROM1 were studied. The average age was 39 years, and 80% were women. The visual acuity was 20/40 at presentation and 20/57 at last follow-up (average 4.8 years). Three distinct macular phenotypes were observed: 1) central geographic atrophy (13%), 2) multifocal geographic atrophy (20%), and 3) bull's eye maculopathy (67%). The overall rate of atrophy progression was 0.36 mm 2 /year, but the average rate of atrophy progression varied by macular phenotype: 1.08 mm 2 /year for central geographic atrophy, 0.53 mm 2 /year for multifocal geographic atrophy, and 0.23 mm 2 /year for bull's eye maculopathy.<br><br>CONCLUSION: Patients with PROM1 -associated macular dystrophy demonstrate distinct phenotypes, with bull's eye maculopathy being the most common. The average rate of atrophy progression may be similar to reported rates for ABCA4 -related Stargardt disease and less than age-related macular degeneration. These results provide important measures for following treatment response in future gene and stem cell-based therapies.},
}
@article {pmid36929056,
year = {2023},
author = {Grimm, NA and Fahimi, S and Kück, F and Take, P and Lauermann, P and Nguyen-Hoehl, A and Hoerauf, H and Feltgen, N and Bemme, S},
title = {Benefit of intravitreal injections in patients with sub-threshold baseline visual acuity: a retrospective single-centre study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {8},
pages = {2421-2429},
pmid = {36929056},
issn = {1435-702X},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; *Angiogenesis Inhibitors/therapeutic use ; Retina ; *Retinal Vein Occlusion/drug therapy ; Visual Acuity ; },
abstract = {PURPOSE: To investigate the lower visual acuity threshold for recommending intravitreal injection therapy (IVI). The lower limit of 1.3 logMAR best-corrected visual acuity (BCVA) was adopted in 2006 and has been maintained since then.<br><br>METHODS: In this retrospective study, data from patients with a logMAR BCVA&#x2009;&#x2264;&#x2009;1.3 and 24&#xa0;months follow-up were analysed. We included patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), or retinal vein occlusion (RVO).<br><br>RESULTS: The data from 164 patients (nAMD: 107; DME: 15; RVO: 42) were analysed. We observed a significant improvement at all time intervals (0 to 6, 6 to 12, 12 to 18, and 18 to 24&#xa0;months after initiating IVI) compared to baseline. Across all indications, median BCVA improved from 1.4 to 1.0 within the first 6&#xa0;months and remained stable within 24&#xa0;months. Patients received a median of 5 and 10 injections within 6 and 24&#xa0;months, respectively. Median foveal retinal thickness was 594.5&#xa0;&#x3bc;m at baseline and dropped to 244.5&#xa0;&#x3bc;m, 235.5&#xa0;&#xb5;m, 183&#xa0;&#xb5;m, and 180&#xa0;&#xb5;m during the four consecutive time intervals.<br><br>CONCLUSION: Patients with nAMD, DME, and RVO with poor baseline BCVA may also benefit from intravitreal therapy with VEGF-inhibitors. In the present study, we observed functional and morphological improvement over 2&#xa0;years irrespective of the underlying macular disease. Those patients should not be excluded from therapy.},
}
@article {pmid36928770,
year = {2023},
author = {Cho, HD and Nhàn, NTT and Zhou, C and Tu, K and Nguyen, T and Sarich, NA and Yamada, KH},
title = {KIF13B mediates VEGFR2 recycling to modulate vascular permeability.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {80},
number = {4},
pages = {91},
pmid = {36928770},
issn = {1420-9071},
support = {P30 EY001792/EY/NEI NIH HHS/United States ; R01 EY029339/EY/NEI NIH HHS/United States ; P30EY001792/NH/NIH HHS/United States ; R01EY029339/NH/NIH HHS/United States ; },
mesh = {Humans ; *Capillary Permeability/genetics/physiology ; Cell Membrane/metabolism ; *Kinesins/metabolism ; Phosphorylation ; Signal Transduction/physiology ; Vascular Endothelial Growth Factor A/metabolism ; *Vascular Endothelial Growth Factor Receptor-2/metabolism ; },
abstract = {Excessive vascular endothelial growth factor-A (VEGF-A) signaling induces vascular leakage and angiogenesis in diseases. VEGFR2 trafficking to the cell surface, mediated by kinesin-3 family protein KIF13B, is essential to respond to VEGF-A when inducing angiogenesis. However, the precise mechanism of how KIF13B regulates VEGF-induced signaling and its effects on endothelial permeability is largely unknown. Here we show that KIF13B-mediated recycling of internalized VEGFR2 through Rab11-positive recycling vesicle regulates endothelial permeability. Phosphorylated VEGFR2 at the cell-cell junction was internalized and associated with KIF13B in Rab5-positive early endosomes. KIF13B mediated VEGFR2 recycling through Rab11-positive recycling vesicle. Inhibition of the function of KIF13B attenuated phosphorylation of VEGFR2 at Y951, SRC at Y416, and VE-cadherin at Y685, which are necessary for endothelial permeability. Failure of VEGFR2 trafficking to the cell surface induced accumulation and degradation of VEGFR2 in lysosomes. Furthermore, in the animal model of the blinding eye disease wet age-related macular degeneration (AMD), inhibition of KIF13B-mediated VEGFR2 trafficking also mitigated vascular leakage. Thus, the present results identify the fundamental role of VEGFR2 recycling to the cell surface in mediating vascular permeability, which suggests a promising strategy for mitigating vascular leakage associated with inflammatory diseases.},
}
@article {pmid36926702,
year = {2023},
author = {Chow, LLC and Mead, B},
title = {Extracellular vesicles as a potential therapeutic for age-related macular degeneration.},
journal = {Neural regeneration research},
volume = {18},
number = {9},
pages = {1876-1880},
pmid = {36926702},
issn = {1673-5374},
abstract = {Age-related macular degeneration is a major global cause of central visual impairment and severe vision loss. With an aging population, the already immense economic burden of costly anti-vascular endothelial growth factor treatment is likely to increase. In addition, current conventional treatment is only available for the late neovascular stage of age-related macular degeneration, and injections can come with potentially devastating complications, introducing the need for more economical and risk-free treatment. In recent years, exosomes, which are nano-sized extracellular vesicles of an endocytic origin, have shown immense potential as diagnostic biomarkers and in the therapeutic application, as they are bestowed with characteristics including an expansive cargo that closely resembles their parent cell and exceptional ability of intercellular communication and targeting neighboring cells. Exosomes are currently undergoing clinical trials for various conditions such as type 1 diabetes and autoimmune diseases; however, exosomes as a potential therapy for several retinal diseases have just begun to undergo scrutinizing investigation with little literature on age-related macular degeneration specifically. This article will focus on the limited literature available on exosome transplantation treatment in age-related macular degeneration animal models and in vitro cell cultures, as well as briefly identify future research directions. Current literature on exosome therapy using age-related macular degeneration rodent models includes laser retinal injury, N-methyl-N-nitrosourea, and royal college of surgeon models, which mimic inflammatory and degenerative aspects of age-related macular degeneration. These have shown promising results in preserving retinal function and morphology, as well as protecting photoreceptors from apoptosis. Exosomes from their respective cellular origins may also act by regulating the expression of various inflammatory cytokines, mRNAs, and proteins involved in photoreceptor degeneration pathways to exert a therapeutic effect. Various findings have also opened exciting prospects for the involvement of cargo components in remedial effects on the damaged macula or retina.},
}
@article {pmid36926522,
year = {2023},
author = {Ascunce, K and Dhodapkar, RM and Huang, D and Hafler, BP},
title = {Innate immune biology in age-related macular degeneration.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1118524},
pmid = {36926522},
issn = {2296-634X},
support = {R01 EY034234/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a neurodegenerative disease and a leading cause of irreversible vision loss in the developed world. While not classically described as an inflammatory disease, a growing body of evidence has implicated several components of the innate immune system in the pathophysiology of age-related macular degeneration. In particular, complement activation, microglial involvement, and blood-retinal-barrier disruption have been shown to play key roles in disease progression, and subsequent vision loss. This review discusses the role of the innate immune system in age-related macular degeneration as well as recent developments in single-cell transcriptomics that help advance the understanding and treatment of age-related macular degeneration. We also explore the several potential therapeutic targets for age-related macular degeneration in the context of innate immune activation.},
}
@article {pmid36925449,
year = {2023},
author = {Hanhart, J and Wiener, R and Totah, H and Brosh, K and Zadok, D},
title = {Pseudophakia as a surprising protective factor in neovascular age-related macular degeneration.},
journal = {Journal francais d'ophtalmologie},
volume = {46},
number = {5},
pages = {527-535},
doi = {10.1016/j.jfo.2022.11.015},
pmid = {36925449},
issn = {1773-0597},
mesh = {Humans ; Angiogenesis Inhibitors ; *COVID-19/complications ; Intravitreal Injections ; *Macular Degeneration/complications/diagnosis/epidemiology ; Protective Factors ; Pseudophakia/epidemiology/complications ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Treatment Outcome ; },
abstract = {PURPOSE: To assess the impact of lens status on macular function among patients treated for neovascular age-related macular degeneration (nvAMD) in whom scheduled intravitreal injections were delayed.<br><br>METHODS: We reviewed demographic and clinical data as well as macular optical coherence tomographic images of 34 patients (48 eyes) who did not follow their injection schedule during the first wave of COVID-19 in Israel. Functional worsening was defined as a loss of at least 0.1 in decimal best-corrected visual acuity (BCVA). Morphological worsening was defined as new or increased subretinal/intraretinal fluid or a new hemorrhage. OCT indices of quality were used as a measure for cataract density and progression.<br><br>RESULTS: Pseudophakia was associated with a better functional outcome than phakic status: there was a loss of 0.06&#xb1;0.12 vs. 0.15&#xb1;0.10 decimal BCVA in the pseudophakic and phakic eyes, respectively (P=.001). A similar trend was observed for morphological changes over the same period: there was an increase in macular thickness of 9&#xb1;26% vs.12&#xb1;40%, respectively (P=0.79). During the first wave of COVID-19, the index of OCT quality remained stable for phakic eyes (26&#xb1;3.6 before the first wave of COVID-19, 26&#xb1;2.9 afterward; P=1) and pseudophakic eyes (30&#xb1;2.4 before the first wave of COVID-19, 30&#xb1;2.6 afterward; P=1).<br><br>CONCLUSION: Pseudophakic eyes with nvAMD that missed their scheduled intravitreal injections experienced fewer morphological and functional complications than phakic eyes with nvAMD.},
}
@article {pmid36924794,
year = {2024},
author = {Basilious, A and Smuck, B and Duncan, J and Malvankar-Mehta, MS and Juncal, VR and Hooper, P and Sheidow, TG},
title = {Patterns of anti-vascular endothelial growth factor discontinuation in neovascular age-related macular degeneration.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {59},
number = {2},
pages = {e161-e169},
doi = {10.1016/j.jcjo.2023.02.006},
pmid = {36924794},
issn = {1715-3360},
mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors ; Endothelial Growth Factors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective cohort study.<br><br>PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021.<br><br>METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups.<br><br>RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 &#xb1; 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (n&#x202f;=&#x202f;152), severe comorbidity or death (n&#x202f;=&#x202f;82), transferred (n&#x202f;=&#x202f;33), stable off active treatment (n&#x202f;=&#x202f;19), lack of benefit plus stable off treatment (n&#x202f;=&#x202f;14), patient decision (n&#x202f;=&#x202f;6), and ocular comorbidity (n&#x202f;=&#x202f;4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (n&#x202f;=&#x202f;178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (p&#x202f;=&#x202f;0.0003), transferred (p&#x202f;=&#x202f;0.0004), and stable off treatment (p&#x202f;=&#x202f;0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (p&#x202f;=&#x202f;0.0055), had better baseline vision (p&#x202f;=&#x202f;0.0018), received more injections (p&#x202f;=&#x202f;0.0437) over a longer time (p&#x202f;=&#x202f;0.0034), and achieved better final vision (p < 0.0001).<br><br>CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.},
}
@article {pmid36924523,
year = {2023},
author = {Kravchenko, SV and Myasnikova, VV and Sakhnov, SN},
title = {Application of the organ-on-a-chip technology in experimental ophthalmology.},
journal = {Vestnik oftalmologii},
volume = {139},
number = {1},
pages = {114-120},
doi = {10.17116/oftalma2023139011114},
pmid = {36924523},
issn = {0042-465X},
mesh = {Humans ; *Ophthalmology ; *Diabetic Retinopathy ; Microphysiological Systems ; *Macular Edema ; *Glaucoma/diagnosis ; },
abstract = {Organ-on-chip is a microfluidic device that can reproduce in vitro the minimal functional unit of an organ or system of organs and model various physiological processes and body structures with high accuracy. This review covers the main approaches to the use of the organ-on-chip technology in modern experimental ophthalmology. The analysis of literature sources revealed the following main applications of the organ-on-chip technology in ophthalmology; the technology allows modeling the anterior eye surface and its diseases, such as dry eye syndrome, as well as disorders of the posterior segment of the eye such as age-related macular degeneration, diabetic macular edema, diabetic retinopathy, glaucoma. Culturing of eye tissues in microfluidic systems helps identify the toxic effects and pharmacological activity of new compounds, and provides an opportunity for deeper understanding of the normal physiology of the eye and the pathogenesis of ocular diseases. In addition, the technology can reduce the cost and duration of experiments. Thus, the organ-on-a-chip technology has a great potential in the field of experimental ophthalmology and preclinical trials of new ophthalmic drugs.},
}
@article {pmid36924516,
year = {2023},
author = {Vasilyeva, TA and Kadyshev, VV and Marakhonov, AV and Kanivets, IV and Korostelev, SA and Koshkin, PA and Pyankov, DV and Petrova, NV and Kutsev, SI and Zinchenko, RA},
title = {[Molecular genetics in diagnosis of Coats disease: combination of oligogenic variants associated with different forms of hereditary retinal dystrophy].},
journal = {Vestnik oftalmologii},
volume = {139},
number = {1},
pages = {69-74},
doi = {10.17116/oftalma202313901169},
pmid = {36924516},
issn = {0042-465X},
mesh = {Humans ; *Retinal Telangiectasis ; *Retinal Dystrophies/diagnosis/genetics ; Mutation ; *Retinitis Pigmentosa ; Pedigree ; Molecular Biology ; },
abstract = {Coats disease (OMIM 300216) is a form of hereditary retinal dystrophy, which occurs due to congenital abnormality of retinal vessels and features unilateral exudative vitreoretinopathy. Coats disease mostly occurs sporadically; its genetic cause is still undetermined. Molecular genetic research including whole exome sequencing by the NGS method was used to define a genetic cause of the observed phenotype. Two heterozygous variants in different genomic loci associated with other forms of hereditary retinal dystrophy were detected, a rare variant in the HMCN1 gene c.9571C>T, p.(Arg3191Cys), and a known pathogenic variant in the NPHP4 gene c.2930C>T, p.(Thr977Met). The HMCN1 gene is responsible for dominant age-related macular degeneration (OMIM 603075), pathogenic variants in the NPHP4 gene cause recessive Senior-Løken syndrome 4 (OMIM 266900). These genes encode the proteins that are involved in the regulation of integrity of the blood-retinal barrier in the vascular endothelium (NPHP4) and retinal pigment epithelium (HMCN1). The identified mutation in the NPHP4 gene could lead to decreased function of the NPHP4 protein and contribute to the development of retinal degeneration, potentially of oligogenic nature.},
}
@article {pmid36922645,
year = {2023},
author = {Xu, Y and Phu, J and Aung, HL and Hesam-Shariati, N and Keay, L and Tully, PJ and Booth, A and Anderson, CS and Anstey, KJ and Peters, R},
title = {Frequency of coexistent eye diseases and cognitive impairment or dementia: a systematic review and meta-analysis.},
journal = {Eye (London, England)},
volume = {37},
number = {15},
pages = {3128-3136},
pmid = {36922645},
issn = {1476-5454},
mesh = {Humans ; *Cognitive Dysfunction/epidemiology/complications ; *Glaucoma/complications/epidemiology ; Aging ; *Diabetic Retinopathy/complications ; *Macular Degeneration ; *Dementia/epidemiology/complications ; },
abstract = {OBJECTIVE: We aim to quantify the co-existence of age-related macular degeneration (AMD), glaucoma, or diabetic retinopathy (DR) and cognitive impairment or dementia.<br><br>METHOD: MEDLINE, EMBASE, PsycINFO and CINAHL were searched (to June 2020). Observational studies reporting incidence or prevalence of AMD, glaucoma, or DR in people with cognitive impairment or dementia, and of cognitive impairment or dementia among people with AMD, glaucoma, or DR were included.<br><br>RESULTS: Fifty-six studies (57 reports) were included but marked by heterogeneities in the diagnostic criteria or definitions of the diseases, study design, and case mix. Few studies reported on the incidence. Evidence was sparse but consistent in individuals with mild cognitive impairment where 7.7% glaucoma prevalence was observed. Prevalence of AMD and DR among people with cognitive impairment ranged from 3.9% to 9.4% and from 11.4% to 70.1%, respectively. Prevalence of AMD and glaucoma among people with dementia ranged from 1.4 to 53% and from 0.2% to 25.9%, respectively. Prevalence of DR among people with dementia was 11%. Prevalence of cognitive impairment in people with AMD, glaucoma, and DR ranged from 8.4% to 52.4%, 12.3% to 90.2%, and 3.9% to 77.8%, respectively, and prevalence of dementia in people with AMD, glaucoma and DR ranged from 9.9% to 62.6%, 2.5% to 3.3% and was 12.5%, respectively.<br><br>CONCLUSIONS: Frequency of comorbid eye disease and cognitive impairment or dementia varied considerably. While more population-based estimations of the co-existence are needed, interdisciplinary collaboration might be helpful in the management of these conditions to meet healthcare needs of an ageing population.<br><br>TRIAL REGISTRATION: PROSPERO registration: CRD42020189484.},
}
@article {pmid36919033,
year = {2023},
author = {William, A and Verma-Fuehring, R and Kuehnel, S and Schwabe, D and Kampik, D and Goebel, W and Hillenkamp, J},
title = {Morphological Macular Changes Under Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration Refractory to Previous Anti-VEGF Treatment Compared with Treatment-Naive Eyes.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {769-777},
pmid = {36919033},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the morphological macular changes and fluid dynamics under brolucizumab treatment in eyes refractory to previous anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) compared with treatment-naive eyes.<br><br>METHODS: Retrospective study of all eyes treated with brolucizumab for nAMD between 2020 and 2021 with a fixed injection regimen and one year follow-up. Treatment-naive eyes (TN) were compared with eyes refractory to previous treatment with bevacizumab, ranibizumab, or aflibercept (RT). The primary outcome measure was change of best-corrected visual acuity (BCVA). Secondary outcome measures included foveal central thickness (FCT), presence of intra- or subretinal fluid (IRF, SRF) and presence of pigment epithelial detachment (PED) at any time point during treatment in both groups.<br><br>RESULTS: Seventeen TN eyes and 17 RT eyes were included. Mean BCVA and mean FCT in TN eyes had significantly improved after 3 months and continued to improve during treatment (p<0.05 and p=0.001, respectively). In RT eyes, mean BCVA did not change significantly while mean FCT had improved after 3 months of treatment and remained stable thereafter. SRF or PED were more frequent in RT eyes compared with TN eyes (p=0.003 and p=0.005, respectively).<br><br>CONCLUSION: After 3 months of treatment, the BCVA increased significantly only in TN eyes, while the FCT was significantly reduced in both groups. IRF appears to be similarly seen in both groups after the loading phase; however, SRF and PED appear to be more frequent in the RT eyes compared with TN eyes.},
}
@article {pmid36918701,
year = {2023},
author = {Khan, AH and Soundara Pandi, SP and Scott, JA and Sánchez-Bretaño, A and Lynn, SA and Ratnayaka, JA and Teeling, JL and Lotery, AJ},
title = {A laser-induced mouse model of progressive retinal degeneration with central sparing displays features of parafoveal geographic atrophy.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {4194},
pmid = {36918701},
issn = {2045-2322},
mesh = {Animals ; Mice ; *Geographic Atrophy/pathology ; *Retinal Degeneration/etiology/pathology ; Fluorescein Angiography/methods ; Retina/diagnostic imaging/pathology ; Tomography, Optical Coherence/methods ; Lasers ; Disease Models, Animal ; Atrophy/pathology ; Retinal Pigment Epithelium/pathology ; },
abstract = {There are no disease-modifying treatments available for geographic atrophy (GA), the advanced form of dry age-related macular degeneration. Current murine models fail to fully recapitulate the features of GA and thus hinder drug discovery. Here we describe a novel mouse model of retinal degeneration with hallmark features of GA. We used an 810 nm laser to create a retinal lesion with central sparing (RLCS), simulating parafoveal atrophy observed in patients with progressive GA. Laser-induced RLCS resulted in progressive GA-like pathology with the development of a confluent atrophic lesion. We demonstrate significant changes to the retinal structure and thickness in the central unaffected retina over a 24-week post-laser period, confirmed by longitudinal optical coherence tomography scans. We further show characteristic features of progressive GA, including a gradual reduction in the thickness of the central, unaffected retina and of total retinal thickness. Histological changes observed in the RLCS correspond to GA pathology, which includes the collapse of the outer nuclear layer, increased numbers of GFAP + , CD11b + and FcγRI + cells, and damage to cone and rod photoreceptors. We demonstrate a laser-induced mouse model of parafoveal GA progression, starting at 2 weeks post-laser and reaching confluence at 24 weeks post-laser. This 24-week time-frame in which GA pathology develops, provides an extended window of opportunity for proof-of-concept evaluation of drugs targeting GA. This time period is an added advantage compared to several existing models of geographic atrophy.},
}
@article {pmid36917350,
year = {2023},
author = {Yao, X and Yang, H and Han, H and Kou, X and Jiang, Y and Luo, M and Zhou, Y and Wang, J and Fan, X and Wang, X and Li, MJ and Yan, H},
title = {Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders.},
journal = {Human genetics},
volume = {142},
number = {4},
pages = {507-522},
pmid = {36917350},
issn = {1432-1203},
support = {82020108007//National Natural Science Foundation of China/ ; 32070675//National Natural Science Foundation of China/ ; 81830026//National Natural Science Foundation of China/ ; 2021YFC2401404//National Key Research and Development Program of China/ ; },
mesh = {Humans ; Genetic Pleiotropy ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; *Macular Degeneration/genetics ; *Glaucoma/genetics ; Polymorphism, Single Nucleotide ; },
abstract = {Age-related macular degeneration (AMD), cataract, and glaucoma are leading causes of blindness worldwide. Previous genome-wide association studies (GWASs) have revealed a variety of susceptible loci associated with age-related ocular disorders, yet the genetic pleiotropy and causal genes across these diseases remain poorly understood. By leveraging large-scale genetic and observational data from ocular disease GWASs and UK Biobank (UKBB), we found significant pairwise genetic correlations and consistent epidemiological associations among these ocular disorders. Cross-disease meta-analysis uncovered seven pleiotropic loci, three of which were replicated in an additional cohort. Integration of variants in pleiotropic loci and multiple single-cell omics data identified that Müller cells and astrocytes were likely trait-related cell types underlying ocular comorbidity. In addition, we comprehensively integrated eye-specific gene expression quantitative loci (eQTLs), epigenomic profiling, and 3D genome data to prioritize causal pleiotropic genes. We found that pleiotropic genes were essential in nerve development and eye pigmentation, and targetable by aflibercept and pilocarpine for the treatment of AMD and glaucoma. These findings will not only facilitate the mechanistic research of ocular comorbidities but also benefit the therapeutic optimization of age-related ocular diseases.},
}
@article {pmid36917317,
year = {2023},
author = {Kai, JY and Xu, Y and Li, DL and Zhou, M and Wang, P and Pan, CW},
title = {Impact of major age-related eye disorders on health-related quality of life assessed by EQ-5D: a systematic review and meta-analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {9},
pages = {2455-2463},
pmid = {36917317},
issn = {1435-702X},
support = {82122059//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Quality of Life ; *Glaucoma/diagnosis/epidemiology ; *Macular Degeneration ; *Cataract ; *Diabetic Retinopathy/diagnosis/epidemiology ; Surveys and Questionnaires ; Health Status ; },
abstract = {PURPOSE: This study is to quantitatively estimate the health-related quality of life (HRQOL) impact of major age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR) assessed by the EuroQoL Five-Dimensional Questionnaire (EQ-5D).<br><br>METHODS: PubMed, Embase, Cochrane Library, and CINAHL were searched until October 20, 2022. Studies were included if they reported the EQ-5D health utility score (HUS) or visual analogue scale (VAS) score of both AREDs patients and healthy controls. The mean difference (MD) in HUS or VAS score between cases and controls and its 95% confidence interval (95%CI) were pooled using the random-effects model. We also performed sensitivity analysis using the leaving-one-out method and subgroup analyses by sample size and race. The prevalence in reporting any problems in the five EQ-5D dimensions was summarized and compared between cases and controls using the Chi-square test.<br><br>RESULTS: Fifteen articles involving 30,491 participants were included in this review. Pooled estimates indicated reduced HUS in AMD patients (MD&#x2009;=&#x2009;-&#xa0;0.04, 95%CI -&#xa0;0.07, -&#xa0;0.01; P&#x2009;=&#x2009;0.009), DR patients (MD&#x2009;=&#x2009;-&#xa0;0.03, 95%CI -&#xa0;0.05, -&#xa0;0.01; P&#x2009;=&#x2009;0.01), and glaucoma patients (MD&#x2009;=&#x2009;-&#xa0;0.06, 95%CI -&#xa0;0.10, -&#xa0;0.01; P&#x2009;=&#x2009;0.01), compared with the controls. Significantly lower EQ-5D VAS score was also observed in cataract patients (MD&#x2009;=&#x2009;-&#xa0;11.33, 95%CI -&#xa0;13.47, -&#xa0;9.18; P&#x2009;<&#x2009;0.001) and DR patients (MD&#x2009;=&#x2009;-&#xa0;6.41, 95%CI -&#xa0;10.64, -&#xa0;2.18; P&#x2009;=&#x2009;0.003). AREDs patients reported usual activities and anxiety/depression problems more frequently than the control group.<br><br>CONCLUSIONS: Our findings confirmed the HRQOL impairment caused by major AREDs including AMD, cataract, DR, and glaucoma. High-quality studies with large sample sizes are warranted to further verify our results.},
}
@article {pmid36917316,
year = {2023},
author = {Ganesh, D and Chiang, JN and Corradetti, G and Zaitlen, N and Halperin, E and Sadda, SR},
title = {Effect of statins on the age of onset of age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {8},
pages = {2245-2255},
pmid = {36917316},
issn = {1435-702X},
mesh = {Humans ; Female ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Retrospective Studies ; Age of Onset ; Fluoxetine ; Risk Factors ; *Macular Degeneration ; Obesity ; },
abstract = {BACKGROUND: This study evaluated the relationship between statin use and the age of onset of age-related macular degeneration (AMD).<br><br>METHODS: Electronic Health Records from 52,840 patients evaluated at University of California Los Angeles (UCLA) Ophthalmology Clinics and 9,977 patients evaluated at University of California San Francisco (UCSF) Ophthalmology Clinics were screened. Survival analysis was performed using Cox proportional hazards regression models and visualized using Kaplan Meier survival curves, with the following covariates-sex, ethnicity, smoking history, fluoxetine use, obesity, diabetes mellitus, and hypertension.<br><br>RESULTS: 5,498 of 52,840 patients at UCLA were diagnosed with AMD. Statin use was associated with a later AMD onset (HR&#x2009;=&#x2009;0.8823, p&#x2009;<&#x2009;0.0001), while female sex (HR&#x2009;=&#x2009;1.0852, p=&#x2009;00,035), obesity (HR&#x2009;=&#x2009;1.4555, p&#x2009;<&#x2009;0.0001), and fluoxetine (HR&#x2009;=&#x2009;1.3797, p=&#x2009;0.0003) were associated with an earlier AMD onset. Non-hispanic black (HR&#x2009;=&#x2009;0.5687, p&#x2009;<&#x2009;0.0001) and hispanic ethnicities (HR&#x2009;=&#x2009;0.8269, p=&#x2009;0.0028) were associated with a later AMD onset. When stratifying for ethnicity, statins, fluoxetine, sex, and obesity were significant only within non-hispanic white subjects. Statin use was significant among patients with dry AMD (HR&#x2009;=&#x2009;0.8410, p=&#x2009;0.0001) but not wet AMD (0.9188, p=&#x2009;0.0351). In the replication cohort, 526 of 9,977 patients at UCSF had AMD. Associations between statins (HR&#x2009;=&#x2009;0.7643, p=&#x2009;0.0033), non-hispanic black ethnicity (HR&#x2009;=&#x2009;0.5043, p=&#x2009;0.0035), and obesity (HR&#x2009;=&#x2009;1.9602, p&#x2009;<&#x2009;0.0001) on AMD onset were confirmed.<br><br>CONCLUSIONS: In both cohorts, statin use and non-hispanic black ethnicity are associated with a later AMD onset, while obesity with an earlier AMD onset.},
}
@article {pmid36917115,
year = {2023},
author = {Shaikh, OA and Amin, S and Shaikh, G and Kumari, K and Ullah, I and Asghar, MS},
title = {Farcimab: a flicker of light in the darkness of neovascular age-related macular degeneration and Diabetes Mellitus - correspondence.},
journal = {International journal of surgery (London, England)},
volume = {109},
number = {4},
pages = {1056-1057},
pmid = {36917115},
issn = {1743-9159},
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Diabetes Mellitus ; Angiogenesis Inhibitors/adverse effects ; },
}
@article {pmid36914803,
year = {2023},
author = {Jones, R and Stratton, IM and Scanlon, PH and Theodoropoulou, S},
title = {Disengagement and loss to follow-up in intravitreal injection clinics for neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {37},
number = {15},
pages = {3186-3190},
pmid = {36914803},
issn = {1476-5454},
mesh = {Humans ; *Ranibizumab ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Follow-Up Studies ; Intravitreal Injections ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Retrospective Studies ; },
abstract = {BACKGROUND/OBJECTIVES: Timely assessment and treatment of patients with neovascular AMD (nAMD) are crucial to preservation of vision. Loss to follow up (LTFU) in these patients is a problem but this has not been systematically investigated.<br><br>SUBJECTS/METHODS: A retrospective review of electronic medical records of patients with nAMD first treated with anti-VEGF therapy from 1st Jan 2014 to 31st Dec 2018, was conducted in January 2021. Any patient not seen for more than 12 months was classed as no longer attending.<br><br>RESULTS: Of the 1328 patients who attended between 2014 and 2018, 348 had failed to attend and were eligible for inclusion in this study. Reasons noted for discontinuation of care: discharged by clinician (33.3%), died (20.7%), moved to another unit outside of area (17.5%), stopped attending due to ill-health (13.5%), discharged due to failure to attend (5.6%) and patient choice to no longer attend (4.6%). There were 16 (4.6%) who did not receive any further appointments despite clinician request for follow-up. After 5 years, 50.5% of patients were no longer attending for treatment. Age was a factor in failure to attend, with 7 out of 12 patients aged >100 years no longer being followed up, compared to 1 out of 11 of 50-59 year-olds.<br><br>CONCLUSIONS: When analysing visual outcomes in an AMD service it is important to characterise the patients who are lost to follow up. The outcomes for this group may be avoidably poor and understanding the factors influencing LTFU rate is crucial to addressing shortcomings in a hospital AMD service.},
}
@article {pmid36913628,
year = {2023},
author = {Grassi, MO and Monteleone, G and Pozharitskiy, N and Molfetta, T and Boscia, G and Alessio, G and Boscia, F},
title = {SEVERE VISUAL LOSS DURING ANTI-VEGF INTRAVITREAL INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: TIMING, PROGNOSIS, AND OPTICAL COHERENCE TOMOGRAPHY FINDINGS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {7},
pages = {1081-1087},
doi = {10.1097/IAE.0000000000003774},
pmid = {36913628},
issn = {1539-2864},
mesh = {Humans ; *Angiogenesis Inhibitors ; Tomography, Optical Coherence ; Intravitreal Injections ; Treatment Outcome ; Ranibizumab/therapeutic use ; Prognosis ; *Macular Degeneration/drug therapy ; Vision Disorders/drug therapy ; },
abstract = {PURPOSE: Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard of care for neovascular age-related macular degeneration (nAMD). However, a small subgroup of patients still experience severe visual impairment, which may be related to the number of IVI administered.<br><br>METHODS: This retrospective observational study analyzed data from patients with sudden severe visual decline (&#x2265;15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss between two consecutive IVIs) during anti-VEGF treatment for nAMD. Best-corrected visual acuity examination, optical coherence tomography (OCT), and OCT angiography (OCTA) were performed before every IVI and central macular thickness (CMT) and drug injected were collected.<br><br>RESULTS: 1,019 eyes received anti-VEGF IVI for nAMD from December 2017 to March 2021. Severe VA loss occurred in 15.1% after a median of 6 (range 1-38) IVI. Ranibizumab was injected in 52.8% and aflibercept in 31.9% of cases. Functional recovery after 3 months was significant, without further improvement at 6 months. Visual prognosis relative to the percentage of CMT change showed better visual outcome in eyes with no substantial change in CMT compared with an increase of >20% or a decrease of >5%.<br><br>CONCLUSION: In this first real-life study exploring severe VA loss during anti-VEGF treatment in patients with nAMD, it was found that it was not unusual for a &#x2265;15 ETDRS letters loss to occur between two consecutive IVIs, often within 9 months of diagnosis and 2 months after the last IVI. Close follow-up and a proactive regimen should be preferred, at least in the first year.},
}
@article {pmid36912591,
year = {2023},
author = {Pawloff, M and Linhardt, D and Woletz, M and Hummer, A and Sacu, S and Vasileiadi, M and Garikoitz, LU and Holder, G and Schmidt-Erfurth, UM and Windischberger, C and Ritter, M},
title = {Comparison of Stimulus Types for Retinotopic Cortical Mapping of Macular Disease.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {3},
pages = {6},
pmid = {36912591},
issn = {2164-2591},
support = {KLI 670/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {Humans ; Brain Mapping/methods ; Visual Fields ; *Visual Cortex/diagnostic imaging/physiology ; *Macular Degeneration/diagnosis ; Fovea Centralis ; *Geographic Atrophy ; },
abstract = {PURPOSE: Retinotopic maps acquired using functional magnetic resonance imaging (fMRI) provide a valuable adjunct in the assessment of macular function at the level of the visual cortex. The present study quantitatively assessed the performance of different visual stimulation approaches for mapping visual field coverage.<br><br>METHODS: Twelve patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were examined using high-resolution ultra-high field fMRI (Siemens Magnetom 7T) and microperimetry (MP; Nidek MP-3). The population receptive field (pRF)-based coverage maps obtained with two different stimulus techniques (moving bars, and rotating wedges and expanding rings) were compared with the results of MP. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient (SMC).<br><br>RESULTS: Stimulus choice is shown to bias the spatial distribution of pRF centers and eccentricity values with pRF sizes obtained from wedge/ring or bar stimulation showing systematic differences. Wedge/ring stimulation results show a higher number of pRF centers in foveal areas and strongly reduced pRF sizes compared to bar stimulation runs. A statistical comparison shows significantly higher pRF center numbers in the foveal 2.5 degrees region of the visual field for wedge/ring compared to bar stimuli. However, these differences do not significantly influence SMC values when compared to MP (bar <2.5 degrees: 0.88 &#xb1; 0.13; bar >2.5 degrees: 0.88 &#xb1; 0.11; wedge/ring <2.5 degrees: 0.89 &#xb1; 0.12 wedge/ring; >2.5 degrees: 0.86 &#xb1; 0.10) for the peripheral visual field.<br><br>CONCLUSIONS: Both visual stimulation designs examined can be applied successfully in patients with GA. Although the two designs show systematic differences in the distribution of pRF center locations, this variability has minimal impact on the SMC when compared to the MP outcome.},
}
@article {pmid36911400,
year = {2023},
author = {Shih, CH and Chuang, HK and Hsiao, TH and Yang, YP and Gao, CE and Chiou, SH and Hsu, CC and Hwang, DK},
title = {Genome-wide association study and identification of systemic comorbidities in development of age-related macular degeneration in a hospital-based cohort of Han Chinese.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1064659},
pmid = {36911400},
issn = {1664-8021},
abstract = {Background: Age-related macular degeneration (AMD) is the main cause of severe vision loss in elderly populations of the developed world with limited therapeutic medications available. It is a multifactorial disease with a strong genetic susceptibility which exhibits the differential genetic landscapes among different ethnic groups. Methods: To investigate the Han Chinese-specific genetic variants for AMD development and progression, we have presented a genome-wide association study (GWAS) on 339 AMD cases and 3,390 controls of a Han Chinese population recruited from the Taiwan Precision Medicine Initiative (TPMI). Results: In this study, we have identified several single nucleotide polymorphisms (SNPs) significantly associated with AMD, including rs10490924, rs3750848, and rs3750846 in the ARMS2 gene, and rs3793917, rs11200638, and rs2284665 in the HTRA1 gene, in which rs10490924 was highly linked to the other variants based upon linkage disequilibrium analysis. Moreover, certain systemic comorbidities, including chronic respiratory diseases and cerebrovascular diseases, were also confirmed to be independently associated with AMD. Stratified analysis revealed that both non-exudative and exudative AMD were significantly correlated with these risk factors. We also found that homozygous alternate alleles of rs10490924 could lead to an increased risk of AMD incidence compared to homozygous references or heterozygous alleles in the cohorts of chronic respiratory disease, cerebrovascular disease, hypertension, and hyperlipidemia. Ultimately, we established the SNP models for AMD risk prediction and found that rs10490924 combined with the other AMD-associated SNPs identified from GWAS improved the prediction model performance. Conclusion: These results suggest that genetic variants combined with the comorbidities could effectively identify any potential individuals at a high risk of AMD, thus allowing for both early prevention and treatment.},
}
@article {pmid36911383,
year = {2023},
author = {Cai, CX and Xiong, XM and Li, T and Liu, BQ and Huang, XH and Yu, SS and Lin, ZQ and Wang, Q and Cui, JL and Lu, L and Lin, Y},
title = {Vortex vein engorgement and different shapes of venous drainage systems in polypoid choroidal vasculopathy vs. age‑related macular degeneration on indocyanine green angiography.},
journal = {Experimental and therapeutic medicine},
volume = {25},
number = {4},
pages = {162},
pmid = {36911383},
issn = {1792-1015},
abstract = {There are differences in vortex vein engorgement and appearance in polypoid choroidal vasculopathy (PCV), age-related macular degeneration (AMD), and healthy eyes. The present study aimed to use indocyanine green angiography (ICGA) to find a simple, clinically meaningful method for evaluating the filling degree of vortex veins in various eye diseases. Participant clinical characteristics were recorded. The number of vortex veins (NVV), central vortex vein diameter (CVVD), mean root area of the vortex vein (MRAVV), mean diameter of the thickest peripheral branch (MDPTB), subfoveal choroidal thickness and percentage of vortex vein anastomosis (PVVA) were obtained by marking the vortex veins on ICGA. The proportion of subretinal haemorrhage and the numbers and types of vortex veins in each quadrant were counted separately. The CVVD and MDPTB were significantly increased in the PCV compared with those in the AMD group (P<0.05). The CVVD, MRAV, and PVVA were significantly increased in the PCV compared with those in the healthy group (P<0.05). The type IV vortex vein (complete with ampulla) proportion was the lowest while the type I (vortex vein absent) proportion was the highest in the PCV group (P<0.001). NVV in the inferior-temporal region was increased in the PCV compared with that in the AMD group (P=0.034). Subretinal haemorrhage occurred in the inferior temporal choroid in 47.62% of examined eyes in PCV group, and in the superior temporal choroid in 23.81% of the PCV group, with significant differences between the quadrants (P<0.001). Vortex vein engorgement and shape differed significantly between PCV, AMD and healthy eyes. The vortex vein branches in PCV eyes were significantly dilated in the posterior pole; moreover, the peripheral choroid and the lower proportion of type IV vortex veins may be pathognomonic for PCV.},
}
@article {pmid36909658,
year = {2023},
author = {Hass, DT and Zhang, Q and Autterson, G and Bryan, R and Hurley, JB and Miller, JM},
title = {Medium depth influences O 2 availability and metabolism in cultured RPE cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.03.01.530623},
pmid = {36909658},
issn = {2692-8205},
support = {K08 EY033420/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: RPE oxidative metabolism is critical for normal retinal function and is often studied in cell culture systems. Here, we show that conventional culture media volumes dramatically impact O 2 availability, limiting oxidative metabolism. We suggest optimal conditions to ensure cultured RPE is in a normoxic environment permissive to oxidative metabolism.<br><br>METHODS: We altered the availability of O 2 to human primary RPE cultures directly via a hypoxia chamber or indirectly via the amount of medium over cells. We measured oxygen consumption rates (OCR), glucose consumption, lactate production, [13] C-glucose flux, hypoxia inducible factor (HIF-1&#x3b1;) stability, intracellular lipid droplets after a lipid challenge, trans-epithelial electrical resistance, cell morphology, and pigmentation.<br><br>RESULTS: Medium volumes commonly employed during RPE culture limit diffusion of O 2 to cells, triggering hypoxia, activating HIF-1&#x3b1;, limiting OCR, and dramatically altering cell metabolism, with only minor effects on typical markers of RPE health. Media volume effects on O 2 availability decrease acetyl-CoA utilization, increase glycolysis, and alter the size and number of intracellular lipid droplets under lipid-rich conditions.<br><br>CONCLUSIONS: Despite having little impact on visible and typical markers of RPE culture health, media volume dramatically affects RPE physiology &#x2033;under the hood&#x2033;. As RPE-centric diseases like age-related macular degeneration (AMD) involve oxidative metabolism, RPE cultures need to be optimized to study such diseases. We provide guidelines for optimal RPE culture volumes that balance ample nutrient availability from larger media volumes with adequate O 2 availability seen with smaller media volumes.},
}
@article {pmid36909148,
year = {2023},
author = {Seddon, JM and Rosner, B and De, D and Huan, T and Java, A and Atkinson, J},
title = {Rare Dysfunctional Complement Factor I Genetic Variants and Progression to Advanced Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {3},
number = {2},
pages = {100265},
pmid = {36909148},
issn = {2666-9145},
support = {R01 EY011309/EY/NEI NIH HHS/United States ; R01 EY022445/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To evaluate associations between rare dysfunctional complement factor I (CFI) genetic variant status and progression to advanced age-related macular degeneration (AAMD), geographic atrophy (GA), and neovascular disease (NV).<br><br>DESIGN: Prospective, longitudinal study.<br><br>PARTICIPANTS: Patients aged 55 to 80 years at baseline identifying as White with non-AAMD in 1 or both eyes at baseline were included. Follow-up grades were assigned as early, intermediate, or AAMD (GA or NV). CFI variants were categorized using genotyping and sequencing platforms.<br><br>METHODS: Analyses were performed using the Seddon Longitudinal Cohort Study (N&#xa0;=&#xa0;2116 subjects, 3901 eyes, and mean follow-up of 8.3 years) and the Age-Related Eye Disease Study (N&#xa0;=&#xa0;2837 subjects, 5200 eyes, and mean follow-up of 9.2 years). CFI rare variants associated with low serum factor I (FI) protein levels and decreased FI function (type 1), other AMD genetic variants, and demographic, behavioral, and ocular factors were evaluated. Generalized estimating equations methods were used to assess the association between CFI rare variants and progression, independent of other genetic variants and covariates.<br><br>MAIN OUTCOME MEASURES: Progression to AAMD, GA, or NV.<br><br>RESULTS: In the prospective cohort of 4953 subjects (9101 eyes with non-AAMD at baseline), 1% were type 1 rare CFI carriers. Over 12 years, progression to AAMD was 44% for carriers and 20% for noncarriers (P < 0.001), 30% of carriers versus 10% of noncarriers progressed to GA (P&#xa0;<&#xa0;0.001), and 18% of carriers compared with 11% of noncarriers progressed to NV (P&#xa0;=&#xa0;0.049). CFI carriers were more likely to have a family history of AMD (P for trend&#xa0;=&#xa0;0.035) and a higher baseline AMD grade (P&#xa0;<&#xa0;0.001). After adjusting for all covariates, CFI carrier status was associated with progression to GA (odds ratio [OR]&#xa0;=&#xa0;1.91; 95% confidence interval [CI]&#xa0;=&#xa0;1.03, 3.52) but not NV (OR&#xa0;=&#xa0;0.96). Higher body mass index was associated with progression among CFI carriers (body mass index &#x2265; 25 vs.&#xa0;<&#xa0;25; OR&#xa0;=&#xa0;5.8; 95% CI 1.5, 22.3) but not for noncarriers (OR&#xa0;=&#xa0;1.1; 95% CI&#xa0;=&#xa0;0.9, 1.3), with P_interaction&#xa0;=&#xa0;0.011.<br><br>CONCLUSIONS: Results suggest that carriers of rare dysfunctional type 1 CFI variants are at higher risk for progression to AAMD with GA.<br><br>FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36908887,
year = {2022},
author = {Ramanoël, S and Durteste, M and Delaux, A and de Saint Aubert, JB and Arleo, A},
title = {Future trends in brain aging research: Visuo-cognitive functions at stake during mobility and spatial navigation.},
journal = {Aging brain},
volume = {2},
number = {},
pages = {100034},
pmid = {36908887},
issn = {2589-9589},
abstract = {Aging leads to a complex pattern of structural and functional changes, gradually affecting sensorimotor, perceptual, and cognitive processes. These multiscale changes can hinder older adults' interaction with their environment, progressively reducing their autonomy in performing tasks relevant to everyday life. Autonomy loss can further be aggravated by the onset and progression of neurodegenerative disorders (e.g., age-related macular degeneration at the sensory input level; and Alzheimer's disease at the cognitive level). In this context, spatial cognition offers a representative case of high-level brain function that involves multimodal sensory processing, postural control, locomotion, spatial orientation, and wayfinding capabilities. Hence, studying spatial behavior and its neural bases can help identify early markers of pathogenic age-related processes. Until now, the neural correlates of spatial cognition have mostly been studied in static conditions thereby disregarding perceptual (other than visual) and motor aspects of natural navigation. In this review, we first demonstrate how visuo-motor integration and the allocation of cognitive resources during locomotion lie at the heart of real-world spatial navigation. Second, we present how technological advances such as immersive virtual reality and mobile neuroimaging solutions can enable researchers to explore the interplay between perception and action. Finally, we argue that the future of brain aging research in spatial navigation demands a widespread shift toward the use of naturalistic, ecologically valid experimental paradigms to address the challenges of mobility and autonomy decline across the lifespan.},
}
@article {pmid36908278,
year = {2023},
author = {Kelly, N and Vukicevic, M and Koklanis, K},
title = {Effectiveness of visual and acoustic biofeedback eccentric viewing training in conjunction with home exercises on visual function: a retrospective observational review.},
journal = {Strabismus},
volume = {31},
number = {1},
pages = {55-65},
doi = {10.1080/09273972.2023.2172435},
pmid = {36908278},
issn = {1744-5132},
mesh = {Humans ; Acoustics ; Biofeedback, Psychology ; Fixation, Ocular ; *Macular Degeneration/complications/rehabilitation ; Retrospective Studies ; *Vision, Low ; Visual Field Tests ; },
abstract = {The aim of this study is to evaluate the effectiveness of an eccentric viewing training program that combines biofeedback training using micro-perimetry with home exercises on multiple visual function parameters and to explore potential relationships between post-treatment visual function parameters. A retrospective observational review of 27 participants who underwent the training program was performed. Eligible participants were diagnosed with bilateral central scotomas secondary to age-related macular degeneration. All participants undertook up to 15 visual and acoustic biofeedback training sessions and were required to partake in traditional home exercises between sessions. The biofeedback training was conducted in the better eye using the Macular Integrity Assessment microperimeter (MAIA). Distance and near acuity, contrast sensitivity and fixation stability quantified by the P1 and P2 values and the 63% and 95% bivariate contour ellipse area (BCEA) before and after the rehabilitation program were recorded. Significant improvement was noted post-training for distance visual acuity (t(26) = 4938 p = .000), near visual acuity (Z = -4.461 p = .000), contrast sensitivity (Z = -3.647 p = .000) and fixation stability for all measures, including P1 (t(26) = -9.490 p = .000), P2 (t(26) = -7.338 p = 0.000), 63% BCEA (Z = 3.569 p = .000) and 95% BCEA (t(26) = 4.687 p = .000). Significant medium-to-large correlations were also found between most visual function variables. Visual and acoustic biofeedback in conjunction with home exercises has the potential to improve visual function parameters in patients with age-related macular degeneration and irreversible central vision loss.},
}
@article {pmid36908254,
year = {2024},
author = {Zhu, A and Tailor, P and Verma, R and Zhang, I and Schott, B and Ye, C and Szirth, B and Habiel, M and Khouri, AS},
title = {Implementation of deep learning artificial intelligence in vision-threatening disease screenings for an underserved community during COVID-19.},
journal = {Journal of telemedicine and telecare},
volume = {30},
number = {10},
pages = {1590-1597},
pmid = {36908254},
issn = {1758-1109},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Artificial Intelligence ; COVID-19 ; *Deep Learning ; Diabetic Retinopathy/diagnosis ; Hispanic or Latino ; Macular Degeneration/diagnosis ; Medically Underserved Area ; New Jersey ; Prospective Studies ; Telemedicine ; *Vision Disorders/diagnosis ; },
abstract = {INTRODUCTION: Age-related macular degeneration, diabetic retinopathy, and glaucoma are vision-threatening diseases that are leading causes of vision loss. Many studies have validated deep learning artificial intelligence for image-based diagnosis of vision-threatening diseases. Our study prospectively investigated deep learning artificial intelligence applications in student-run non-mydriatic screenings for an underserved, primarily Hispanic community during COVID-19.<br><br>METHODS: Five supervised student-run community screenings were held in West New York, New Jersey. Participants underwent non-mydriatic 45-degree retinal imaging by medical students. Images were uploaded to a cloud-based deep learning artificial intelligence for vision-threatening disease referral. An on-site tele-ophthalmology grader and remote clinical ophthalmologist graded images, with adjudication by a senior ophthalmologist to establish the gold standard diagnosis, which was used to assess the performance of deep learning artificial intelligence.<br><br>RESULTS: A total of 385 eyes from 195 screening participants were included (mean age 52.43&#x2009;&#x2009;&#xb1;&#x2009;&#x2009;14.5 years, 40.0% female). A total of 48 participants were referred for at least one vision-threatening disease. Deep learning artificial intelligence marked 150/385 (38.9%) eyes as ungradable, compared to 10/385 (2.6%) ungradable as per the human gold standard (p&#x2009;<&#x2009;0.001). Deep learning artificial intelligence had 63.2% sensitivity, 94.5% specificity, 32.0% positive predictive value, and 98.4% negative predictive value in vision-threatening disease referrals. Deep learning artificial intelligence successfully referred all 4 eyes with multiple vision-threatening diseases. Deep learning artificial intelligence graded images (35.6&#x2009;&#x2009;&#xb1;&#x2009;&#x2009;13.3&#x2005;s) faster than the tele-ophthalmology grader (129&#x2009;&#x2009;&#xb1;&#x2009;&#x2009;41.0) and clinical ophthalmologist (68&#x2009;&#x2009;&#xb1;&#x2009;&#x2009;21.9, p&#x2009;<&#x2009;0.001).<br><br>DISCUSSION: Deep learning artificial intelligence can increase the efficiency and accessibility of vision-threatening disease screenings, particularly in underserved communities. Deep learning artificial intelligence should be adaptable to different environments. Consideration should be given to how deep learning artificial intelligence can best be utilized in a real-world application, whether in computer-aided or autonomous diagnosis.},
}
@article {pmid36908237,
year = {2023},
author = {Yokomizo, T and Shimizu, T},
title = {The leukotriene B4 receptors BLT1 and BLT2 as potential therapeutic targets.},
journal = {Immunological reviews},
volume = {317},
number = {1},
pages = {30-41},
doi = {10.1111/imr.13196},
pmid = {36908237},
issn = {1600-065X},
mesh = {Mice ; Humans ; Animals ; *Leukotriene B4 ; *Asthma ; Skin ; Wound Healing ; Receptors, Leukotriene B4/genetics ; },
abstract = {Leukotriene B4 (LTB4) was recognized as an arachidonate-derived chemotactic factor for inflammatory cells and an important drug target even before the molecular identification of its receptors. We cloned the high- and low-affinity LTB4 receptors, BLT1 and BLT2, respectively, and examined their functions by generating and studying gene-targeted mice. BLT1 is involved in the pathogenesis of various inflammatory and immune diseases, including asthma, psoriasis, contact dermatitis, allergic conjunctivitis, age-related macular degeneration, and immune complex-mediated glomerulonephritis. Meanwhile, BLT2 is a high-affinity receptor for 12-hydroxyheptadecatrienoic acid, which is involved in the maintenance of dermal and intestinal barrier function, and the acceleration of skin and corneal wound healing. Thus, BLT1 antagonists and BLT2 agonists are promising candidates in the treatment of inflammatory diseases.},
}
@article {pmid36906669,
year = {2023},
author = {Gotfredsen, K and Liisborg, C and Skov, V and Kjær, L and Hasselbalch, HC and Sørensen, TL},
title = {Serum levels of IL-4, IL-13 and IL-33 in patients with age-related macular degeneration and myeloproliferative neoplasms.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {4077},
pmid = {36906669},
issn = {2045-2322},
mesh = {Humans ; Interleukin-4 ; Interleukin-13 ; Angiogenesis Inhibitors ; Interleukin-33 ; Cross-Sectional Studies ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; *Neoplasms ; Cytokines ; Inflammation ; },
abstract = {Immune responses play a key role in the pathogenesis and progression of myeloproliferative neoplasms (MPN) and age-related macular degeneration (AMD). Recent studies suggested using MPNs as a "Human Inflammation Model" of drusen development and previous results showed interleukin-4 (IL-4) dysregulation in MPN and AMD. IL-4, IL-13 and IL-33 are all cytokines involved in the type 2 inflammatory response. This study investigated the cytokine levels of IL-4, IL-13 and IL-33 in serum of MPN and AMD patients. This cross-sectional study included 35 patients with MPN with drusen (MPNd) and 27 with MPN and normal retinas (MPNn), 28 patients with intermediate AMD (iAMD) and 29 with neovascular AMD (nAMD). With immunoassays, we quantified and compared levels of IL-4, IL-13 and IL-33 in serum between the groups. The study was conducted at Zealand University Hospital, Roskilde, Denmark, between July 2018 and November 2020. The serum levels of IL-4 were significantly higher in the MPNd group than in the MPNn group (p = 0.003). In regard to IL-33, the difference between MPNd and MPNn was not significant (p = 0.069), however, when subdivided into subgroups, a significant difference was found between polycythemia vera patients with drusen and those without drusen (p = 0.005). We found no IL-13 difference between the MPNd and MPNn groups. Our data didn't show any significant IL-4 or IL-13 serum level difference between the MPNd and iAMD groups but in regard to IL-33, data recorded a significant serum level difference between the two groups. There was no statistically significant difference between the MPNn, iAMD and nAMD groups in levels of IL-4, IL-13 and IL-33. These findings suggested that the serum levels of IL-4 and IL-33 might play a role in drusen development in MPN patients. The results might represent the type 2 inflammatory arm of the disease. The findings support the association between chronic inflammation and drusen.},
}
@article {pmid36906177,
year = {2023},
author = {Freeman, WR and Bandello, F and Souied, E and Guymer, RH and Garg, SJ and Chen, FK and Rich, R and Holz, FG and Patel, SS and Kim, K and López, FJ and , },
title = {Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {7},
pages = {573-585},
doi = {10.1016/j.oret.2023.03.001},
pmid = {36906177},
issn = {2468-6530},
mesh = {Humans ; *Geographic Atrophy/diagnosis/drug therapy/etiology ; *Macular Degeneration/complications/diagnosis/drug therapy ; Retina ; Drug Delivery Systems/adverse effects ; Intravitreal Injections ; },
abstract = {PURPOSE: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).<br><br>DESIGN: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON).<br><br>PARTICIPANTS: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm[2] and &#x2264; 18 mm[2] in the study eye.<br><br>METHODS: Enrolled patients were randomized to treatment with intravitreal injections of 400-&#x3bc;g Brimo DDS (n&#xa0;= 154) or sham procedure (n&#xa0;= 156) in the study eye every 3 months from day 1 to month&#xa0;21.<br><br>MAIN OUTCOME MEASURES: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24.<br><br>RESULTS: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (&#x223c; 1.6 mm[2]/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm[2] with Brimo DDS (n&#xa0;= 84) versus 3.48 (0.13) mm[2] with sham (n&#xa0;= 91), a reduction of 0.25 mm[2] (7%) with Brimo DDS compared with sham (P&#xa0;= 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm[2] with Brimo DDS (n&#xa0;= 49) versus 4.52 (0.15) mm[2] with sham (n&#xa0;= 46), a reduction of 0.43 mm[2] (10%) with Brimo DDS compared with sham (P&#xa0;= 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P&#xa0;= 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed.<br><br>CONCLUSIONS: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.},
}
@article {pmid36906094,
year = {2023},
author = {Newman-Casey, PA and Niziol, LM and Elam, AR and Bicket, AK and Killeen, O and John, D and Wood, SD and Musch, DC and Zhang, J and Johnson, L and Kershaw, M and Woodward, MA},
title = {Michigan Screening and Intervention for Glaucoma and Eye Health Through Telemedicine Program: First-Year Outcomes and Implementation Costs.},
journal = {American journal of ophthalmology},
volume = {251},
number = {},
pages = {43-51},
pmid = {36906094},
issn = {1879-1891},
support = {K12 EY022299/EY/NEI NIH HHS/United States ; K23 MD016430/MD/NIMHD NIH HHS/United States ; U01 DP006442/DP/NCCDPHP CDC HHS/United States ; },
mesh = {Humans ; Male ; Middle Aged ; Female ; Michigan/epidemiology ; Cohort Studies ; *Glaucoma/diagnosis/epidemiology ; *Ocular Hypertension/diagnosis ; *Telemedicine/methods ; },
abstract = {PURPOSE: The Michigan Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (MI-SIGHT) program aims to engage people who are at high risk of glaucoma; we assess first-year outcomes and costs.<br><br>DESIGN: Clinical cohort study.<br><br>METHODS: Participants &#x2265;18 years of age were recruited from a free clinic and a federally qualified health center in Michigan. Ophthalmic technicians in the clinics collected demographic information, visual function, ocular health history, measured visual acuity, refraction, intraocular pressure, pachymetry, pupils, and took mydriatic fundus photographs and retinal nerve fiber layer optical coherence tomography. Data were interpreted by remote ophthalmologists. During a follow-up visit, technicians shared ophthalmologist recommendations, dispensed low-cost glasses, and collected participant satisfaction. The primary outcome measures were prevalence of eye disease, visual function, program satisfaction, and costs. Observed prevalence was compared with national disease prevalence rates using z tests of proportions.<br><br>RESULTS: Among 1171 participants, the average age was 55 years (SD 14.5 years), 38% were male, 54% identified as Black, 34% as White, 10% as Hispanic, 33% had less than or equal to a high school education, and 70% had an annual income <$30,000. The prevalence of visual impairment was 10.3% (national average 2.2%), glaucoma and suspected glaucoma 24% (national average 9%), macular degeneration 2.0% (national average 1.5%), and diabetic retinopathy 7.3% (national average 3.4%) (P < .0001). Seventy-one percent of participants received low-cost glasses, 41% were referred for ophthalmology follow-up, and 99% were satisfied or very satisfied with the program. Startup costs were $103,185; recurrent costs were $248,103 per clinic.<br><br>CONCLUSIONS: Telemedicine eye disease detection programs in low-income community clinics effectively identify high rates of pathology.},
}
@article {pmid36905808,
year = {2023},
author = {Ku, LC and Sheu, ML and Cheng, HH and Lee, CY and Tsai, YC and Tsai, CY and Lin, KH and Lai, LC and Lai, DW},
title = {Melatonin protects retinal integrity through mediated immune homeostasis in the sodium iodate-induced mouse model of age-related macular degeneration.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {161},
number = {},
pages = {114476},
doi = {10.1016/j.biopha.2023.114476},
pmid = {36905808},
issn = {1950-6007},
mesh = {Mice ; Animals ; Humans ; Aged ; *Melatonin/pharmacology/metabolism ; Retina/pathology ; *Macular Degeneration/chemically induced/genetics ; Disease Models, Animal ; Homeostasis ; Retinal Pigment Epithelium ; },
abstract = {BACKGROUND: Age-related macular degeneration is the leading cause of visual deficiency in older adults worldwide. Melatonin (MT) can potentially reduce retinal deterioration. However, the mechanism by which MT mediates regulatory T cells (Tregs) in the retina is not yet fully understood.<br><br>METHODS: The transcriptome profiles of aged or young human retinal tissues from the GEO database were analyzed for MT-related gene expression. The pathological changes in the retina in the NaIO3-induced mouse model were quantitatively determined by staining with hematoxylin and eosin. Retinal whole-mounting immunofluorescence staining was conducted to determine the expression of the Treg-specific marker FOXP3. The phenotypes of M1/M2 macrophages were representing related gene markers in the retina. The GEO database includes biopsies from patients with retinal detachment for ENPTD1, NT5E, and TET2 gene expression. A pyrosequencing assay was performed for NT5E DNA methylation on human primary Tregs, and siTET2 transfection engineering was used.<br><br>RESULTS: MT synthesis-related genes in retinal tissue may be affected by age. Our study shows that MT can effectively restore NaIO3-induced retinopathy and maintain retinal structural integrity. Importantly, MT may assist the conversion of M1 to M2 macrophages to promote tissue repair, which may be caused by the increased infiltration of Tregs. Moreover, MT treatment may upregulate TET2, and further NT5E demethylation is associated with Treg recruitment in the retinal microenvironment.<br><br>CONCLUSIONS: Our findings suggest that MT can effectively ameliorate retinal degeneration and regulate immune homeostasis via Tregs. Modulation of the immune response may provide a key therapeutic strategy.},
}
@article {pmid36904215,
year = {2023},
author = {Fu, Y and Chen, X and Luo, S and Jiang, S and Mao, Y and Xiao, W},
title = {Serum 25-Hydroxyvitamin D Is Differentially Associated with Early and Late Age-Related Macular Degeneration in the United States Population.},
journal = {Nutrients},
volume = {15},
number = {5},
pages = {},
pmid = {36904215},
issn = {2072-6643},
support = {2023A1515012192;//Natural Science Foundation of Guangdong Province, China:/ ; 2023A1515030108//Natural Science Foundation of Guangdong Province, China:/ ; 81600751//National Natural Science Foundation of China:/ ; 81700820//National Natural Science Foundation of China:/ ; 201806010167//the Pearl River Nova Program of Guangzhou:/ ; },
mesh = {Humans ; United States ; Middle Aged ; Nutrition Surveys ; Risk Factors ; *Vitamin D ; *Macular Degeneration/epidemiology ; Calcifediol ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) has been the leading cause of irreversible blindness in industrialized countries. Emerging data suggest that serum vitamin D levels may be associated with AMD but show mixed results. National-level population data on the relationship between vitamin D and AMD severities are still lacking.<br><br>METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2008. Retinal photographs were taken and graded for AMD stage. The odds ratio (OR) of AMD and its subtype was calculated after adjusting for confounding factors. Restricted cubic spline (RCS) analyses were used to explore potential non-linear relations.<br><br>RESULTS: A total of 5041 participants with a mean age of 59.6 years were included. After adjusting for covariates, participants with higher level of serum 25-hydroxyvitamin D [25(OH)D] had significantly greater odds of early AMD (OR, 1.65; 95% CI, 1.08-2.51) and decreased risk of late AMD (OR, 0.29; 95% CI, 0.09-0.88). When stratified by age, a positive association between the level of serum 25(OH)D and early AMD was present in the <60 years group (OR, 2.79; 95% CI, 1.08-7.29), whereas a negative relation between the level of serum 25(OH)D and late AMD was detected in the &#x2265;60 years group (OR, 0.24; 95% CI, 0.08-0.76).<br><br>CONCLUSIONS: A higher level of serum 25(OH)D was related to increased risk of early AMD in those <60 years and decreased risk of late AMD in those &#x2265;60 years.},
}
@article {pmid36903482,
year = {2023},
author = {Pan, S and Liu, M and Xu, H and Chuan, J and Yang, Z},
title = {Lipopolysaccharide Activating NF-kB Signaling by Regulates HTRA1 Expression in Human Retinal Pigment Epithelial Cells.},
journal = {Molecules (Basel, Switzerland)},
volume = {28},
number = {5},
pages = {},
pmid = {36903482},
issn = {1420-3049},
support = {81790643, 82121003 and 82101163//National Natural Science Foundation of China/ ; 2021YFS0404, 2021YFS0369 and 2021YFS0388//Sichuan Province Science and Technology Support Program/ ; 2019-12M-5-032//CAMS Innovation Fund for Medical Sciences/ ; 2021LY23//Clinical Research Foundation of Sichuan Provincial People's Hospital/ ; },
mesh = {Humans ; *NF-kappa B/metabolism ; High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism/pharmacology ; Lipopolysaccharides/pharmacology ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/metabolism ; Inflammation/drug therapy ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Inflammation and elevated expression of high temperature requirement A serine peptidase 1 (HTRA1) are known high risk factors for age-related macular degeneration (AMD). However, the specific mechanism that HTRA1 causes AMD and the relationship between HTRA1 and inflammation remains unclear. We found that lipopolysaccharide (LPS) induced inflammation enhanced the expression of HTRA1, NF-κB, and p-p65 in ARPE-19 cells. Overexpression of HTRA1 up-regulated NF-κB expression, and on the other hand knockdown of HTRA1 down-regulated the expression of NF-κB. Moreover, NF-κB siRNA has no significant effect on the expression of HTRA1, suggesting HTRA1 works upstream of NF-κB. These results demonstrated that HTRA1 plays a pivotal role in inflammation, explaining possible mechanism of overexpressed HTRA1-induced AMD. Celastrol, a very common anti-inflammatory and antioxidant drug, was found to suppress inflammation by inhibiting phosphorylation of p65 protein efficaciously in RPE cells, which may be applied to the therapy of age-related macular degeneration.},
}
@article {pmid36902750,
year = {2023},
author = {Krytkowska, E and Ulańczyk, Z and Grabowicz, A and Safranow, K and Kawa, MP and Pałucha, A and Wąsowska, A and Matczyńska, E and Boguszewska-Chachulska, A and Machalińska, A},
title = {Influence of Clinical and Genetic Factors on the Progression of Age-Related Macular Degeneration: A 3-Year Follow-Up.},
journal = {Journal of clinical medicine},
volume = {12},
number = {5},
pages = {},
pmid = {36902750},
issn = {2077-0383},
support = {STRATEGMED1/234261/2NCBR/2014//Polish National Centre for Research and Development/ ; },
abstract = {The aim of the present study was to analyze the relationship of age-related macular degeneration (AMD) progression with clinical characteristics, demographic, and environmental risk factors that would affect disease development. In addition, the influence of three genetic AMD polymorphisms (CFH Y402H, ARMS2 A69S, and PRPH2 c.582-67T>A) on AMD progression was investigated. In total, 94 participants with previously diagnosed early or intermediate AMD in at least one eye were recalled for an updated re-evaluation after 3 years. The initial visual outcomes, medical history, retinal imaging data, and choroidal imaging data were collected to characterize the AMD disease status. Among the AMD patients, 48 demonstrated AMD progression, and 46 showed no disease worsening at 3 years. Disease progression was significantly associated with worse initial visual acuity (OR = 6.74, 95% CI = 1.24-36.79, p = 0.03) and the presence of the wet AMD subtype in fellow eyes (OR = 3.79, 95%CI = 0.94-15.2, p = 0.05). In addition, a higher risk of AMD progression appeared in the patients with active thyroxine supplementation (OR = 4.77, CI = 1.25-18.25, p = 0.002). The CC variant of CFH Y402H was associated with AMD advancement compared to the TC+TT phenotype (OR = 2.76, 95% CI: 0.98-7.79, p = 0.05). Identifying risk factors of AMD progression may lead to earlier intervention and better outcomes, preventing the expansion of the late stage of the disease.},
}
@article {pmid36902225,
year = {2023},
author = {Jin, M and Zhang, XY and Ying, Q and Hu, HJ and Feng, XT and Peng, Z and Pang, YL and Yan, F and Zhang, X},
title = {Antioxidative and Mitochondrial Protection in Retinal Pigment Epithelium: New Light Source in Action.},
journal = {International journal of molecular sciences},
volume = {24},
number = {5},
pages = {},
pmid = {36902225},
issn = {1422-0067},
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism ; *Antioxidants/pharmacology ; Oxidative Stress/radiation effects ; Zebrafish/metabolism ; Hydrogen Peroxide/metabolism ; Reactive Oxygen Species/metabolism ; Light ; },
abstract = {Low-color-temperature light-emitting diodes (LEDs) (called 1900 K LEDs for short) have the potential to become a healthy light source due to their blue-free property. Our previous research demonstrated that these LEDs posed no harm to retinal cells and even protected the ocular surface. Treatment targeting the retinal pigment epithelium (RPE) is a promising direction for age-related macular degeneration (AMD). Nevertheless, no study has evaluated the protective effects of these LEDs on RPE. Therefore, we used the ARPE-19 cell line and zebrafish to explore the protective effects of 1900 K LEDs. Our results showed that the 1900 K LEDs could increase the cell vitality of ARPE-19 cells at different irradiances, with the most pronounced effect at 10 W/m[2]. Moreover, the protective effect increased with time. Pretreatment with 1900 K LEDs could protect the RPE from death after hydrogen peroxide (H2O2) damage by reducing reactive oxygen species (ROS) generation and mitochondrial damage caused by H2O2. In addition, we preliminarily demonstrated that irradiation with 1900 K LEDs in zebrafish did not cause retinal damage. To sum up, we provide evidence for the protective effects of 1900 K LEDs on the RPE, laying the foundation for future light therapy using these LEDs.},
}
@article {pmid36901754,
year = {2023},
author = {Zhang, X and Xu, J and Marshall, B and Dong, Z and Liu, Y and Espinosa-Heidmann, DG and Zhang, M},
title = {Transcriptome Analysis of Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection.},
journal = {International journal of molecular sciences},
volume = {24},
number = {5},
pages = {},
pmid = {36901754},
issn = {1422-0067},
support = {P30 EY031631/EY/NEI NIH HHS/United States ; R01 EY026642/EY/NEI NIH HHS/United States ; R21 EY028671/EY/NEI NIH HHS/United States ; RO1 EY026642/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; Mice, Inbred BALB C ; *Eye Infections, Viral/metabolism/pathology ; *Cytomegalovirus Infections ; Choroid/metabolism ; *Muromegalovirus/physiology ; Gene Expression Profiling ; },
abstract = {Our previous studies have shown that systemic neonatal murine cytomegalovirus (MCMV) infection of BALB/c mice spread to the eye with subsequent establishment of latency in choroid/RPE. In this study, RNA sequencing (RNA-Seq) analysis was used to determine the molecular genetic changes and pathways affected by ocular MCMV latency. MCMV (50 pfu per mouse) or medium as control were injected intra-peritoneally (i.p.) into BALB/c mice at <3 days after birth. At 18 months post injection, the mice were euthanized, and the eyes were collected and prepared for RNA-Seq. Compared to three uninfected control eyes, we identified 321 differentially expressed genes (DEGs) in six infected eyes. Using the QIAGEN Ingenuity Pathway Analysis (QIAGEN IPA), we identified 17 affected canonical pathways, 10 of which function in neuroretinal signaling, with the majority of DEGs being downregulated, while 7 pathways function in upregulated immune/inflammatory responses. Retinal and epithelial cell death pathways involving both apoptosis and necroptosis were also activated. MCMV ocular latency is associated with upregulation of immune and inflammatory responses and downregulation of multiple neuroretinal signaling pathways. Cell death signaling pathways are also activated and contribute to the degeneration of photoreceptors, RPE, and choroidal capillaries.},
}
@article {pmid36900119,
year = {2023},
author = {Friedmann, E and Dörsam, S and Auffarth, GU},
title = {Models and Algorithms for the Refinement of Therapeutic Approaches for Retinal Diseases.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {5},
pages = {},
pmid = {36900119},
issn = {2075-4418},
support = {00.265.2015//Klaus Tschira Foundation/ ; },
abstract = {We are developing a Virtual Eye for in silico therapies to accelerate research and drug development. In this paper, we present a model for drug distribution in the vitreous body that enables personalized therapy in ophthalmology. The standard treatment for age-related macular degeneration is anti-vascular endothelial growth factor (VEGF) drugs administered by repeated injections. The treatment is risky, unpopular with patients, and some of them are unresponsive with no alternative treatment. Much attention is paid to the efficacy of these drugs, and many efforts are being made to improve them. We are designing a mathematical model and performing long-term three-dimensional Finite Element simulations for drug distribution in the human eye to gain new insights in the underlying processes using computational experiments. The underlying model consists of a time-dependent convection-diffusion equation for the drug coupled with a steady-state Darcy equation describing the flow of aqueous humor through the vitreous medium. The influence of collagen fibers in the vitreous on drug distribution is included by anisotropic diffusion and the gravity via an additional transport term. The resulting coupled model was solved in a decoupled way: first the Darcy equation with mixed finite elements, then the convection-diffusion equation with trilinear Lagrange elements. Krylov subspace methods are used to solve the resulting algebraic system. To cope with the large time steps resulting from the simulations over 30 days (operation time of 1 anti-VEGF injection), we apply the strong A-stable fractional step theta scheme. Using this strategy, we compute a good approximation to the solution that converges quadratically in both time and space. The developed simulations were used for the therapy optimization, for which specific output functionals are evaluated. We show that the effect of gravity on drug distribution is negligible, that the optimal pair of injection angles is (50∘,50∘), that larger angles can result in 38% less drug at the macula, and that in the best case only 40% of the drug reaches the macula while the rest escapes, e.g., through the retina, that by using heavier drug molecules, more of the drug concentration reaches the macula in an average of 30 days. As a refined therapy, we have found that for longer-acting drugs, the injection should be made in the center of the vitreous, and for more intensive initial treatment, the drug should be injected even closer to the macula. In this way, we can perform accurate and efficient treatment testing, calculate the optimal injection position, perform drug comparison, and quantify the effectiveness of the therapy using the developed functionals. We describe the first steps towards virtual exploration and improvement of therapy for retinal diseases such as age-related macular degeneration.},
}
@article {pmid36899935,
year = {2023},
author = {Lin, LW and Wang, SW and Huang, WC and Huynh, TK and Lai, CY and Ko, CY and Fong, YC and Lee, JJ and Yang, SF and Tang, CH},
title = {Melatonin Inhibits VEGF-Induced Endothelial Progenitor Cell Angiogenesis in Neovascular Age-Related Macular Degeneration.},
journal = {Cells},
volume = {12},
number = {5},
pages = {},
pmid = {36899935},
issn = {2073-4409},
mesh = {Humans ; Angiogenesis Inhibitors ; *Endothelial Progenitor Cells ; *Melatonin ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; },
abstract = {Neovascular age-related macular degeneration (AMD) is described as abnormal angiogenesis in the retina and the leaking of fluid and blood that generates a huge, dark, blind spot in the center of the visual field, causing severe vision loss in over 90% of patients. Bone marrow-derived endothelial progenitor cells (EPCs) contribute to pathologic angiogenesis. Gene expression profiles downloaded from the eyeIntegration v1.0 database for healthy retinas and retinas from patients with neovascular AMD identified significantly higher levels of EPC-specific markers (CD34, CD133) and blood vessel markers (CD31, VEGF) in the neovascular AMD retinas compared with healthy retinas. Melatonin is a hormone that is mainly secreted by the pineal gland, and is also produced in the retina. Whether melatonin affects vascular endothelial growth factor (VEGF)-induced EPC angiogenesis in neovascular AMD is unknown. Our study revealed that melatonin inhibits VEGF-induced stimulation of EPC migration and tube formation. By directly binding with the VEGFR2 extracellular domain, melatonin significantly and dose-dependently inhibited VEGF-induced PDGF-BB expression and angiogenesis in EPCs via c-Src and FAK, NF-κB and AP-1 signaling. The corneal alkali burn model demonstrated that melatonin markedly inhibited EPC angiogenesis and neovascular AMD. Melatonin appears promising for reducing EPC angiogenesis in neovascular AMD.},
}
@article {pmid36899910,
year = {2023},
author = {Emri, E and Cappa, O and Kelly, C and Kortvely, E and SanGiovanni, JP and McKay, BS and Bergen, AA and Simpson, DA and Lengyel, I},
title = {Zinc Supplementation Induced Transcriptional Changes in Primary Human Retinal Pigment Epithelium: A Single-Cell RNA Sequencing Study to Understand Age-Related Macular Degeneration.},
journal = {Cells},
volume = {12},
number = {5},
pages = {},
pmid = {36899910},
issn = {2073-4409},
support = {FS/19/28/34358/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism ; Zinc/metabolism ; *Macular Degeneration/metabolism ; Gene Expression Profiling ; Sequence Analysis, RNA ; },
abstract = {Zinc supplementation has been shown to be beneficial to slow the progression of age-related macular degeneration (AMD). However, the molecular mechanism underpinning this benefit is not well understood. This study used single-cell RNA sequencing to identify transcriptomic changes induced by zinc supplementation. Human primary retinal pigment epithelial (RPE) cells could mature for up to 19 weeks. After 1 or 18 weeks in culture, we supplemented the culture medium with 125 µM added zinc for one week. RPE cells developed high transepithelial electrical resistance, extensive, but variable pigmentation, and deposited sub-RPE material similar to the hallmark lesions of AMD. Unsupervised cluster analysis of the combined transcriptome of the cells isolated after 2, 9, and 19 weeks in culture showed considerable heterogeneity. Clustering based on 234 pre-selected RPE-specific genes divided the cells into two distinct clusters, we defined as more and less differentiated cells. The proportion of more differentiated cells increased with time in culture, but appreciable numbers of cells remained less differentiated even at 19 weeks. Pseudotemporal ordering identified 537 genes that could be implicated in the dynamics of RPE cell differentiation (FDR < 0.05). Zinc treatment resulted in the differential expression of 281 of these genes (FDR < 0.05). These genes were associated with several biological pathways with modulation of ID1/ID3 transcriptional regulation. Overall, zinc had a multitude of effects on the RPE transcriptome, including several genes involved in pigmentation, complement regulation, mineralization, and cholesterol metabolism processes associated with AMD.},
}
@article {pmid36899848,
year = {2023},
author = {Carlsson, E and Sharif, U and Supharattanasitthi, W and Paraoan, L},
title = {Analysis of Wild Type and Variant B Cystatin C Interactome in Retinal Pigment Epithelium Cells Reveals Variant B Interacting Mitochondrial Proteins.},
journal = {Cells},
volume = {12},
number = {5},
pages = {},
pmid = {36899848},
issn = {2073-4409},
mesh = {Humans ; *Cystatin C ; Retinal Pigment Epithelium/metabolism ; Mitochondrial Proteins/metabolism ; *Macular Degeneration/metabolism ; Mitochondria/metabolism ; Receptors, GABA/metabolism ; },
abstract = {Cystatin C, a secreted cysteine protease inhibitor, is abundantly expressed in retinal pigment epithelium (RPE) cells. A mutation in the protein's leader sequence, corresponding to formation of an alternate variant B protein, has been linked with an increased risk for both age-related macular degeneration (AMD) and Alzheimer's disease (AD). Variant B cystatin C displays intracellular mistrafficking with partial mitochondrial association. We hypothesized that variant B cystatin C interacts with mitochondrial proteins and impacts mitochondrial function. We sought to determine how the interactome of the disease-related variant B cystatin C differs from that of the wild-type (WT) form. For this purpose, we expressed cystatin C Halo-tag fusion constructs in RPE cells to pull down proteins interacting with either the WT or variant B form, followed by identification and quantification by mass spectrometry. We identified a total of 28 interacting proteins, of which 8 were exclusively pulled down by variant B cystatin C. These included 18 kDa translocator protein (TSPO) and cytochrome B5 type B, both of which are localized to the mitochondrial outer membrane. Variant B cystatin C expression also affected RPE mitochondrial function with increased membrane potential and susceptibility to damage-induced ROS production. The findings help us to understand how variant B cystatin C differs functionally from the WT form and provide leads to RPE processes adversely affected by the variant B genotype.},
}
@article {pmid36896135,
year = {2023},
author = {Rajala, A and Bhat, MA and Teel, K and Gopinadhan Nair, GK and Purcell, L and Rajala, RVS},
title = {The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases.},
journal = {PNAS nexus},
volume = {2},
number = {3},
pages = {pgad038},
pmid = {36896135},
issn = {2752-6542},
support = {P30 EY012190/EY/NEI NIH HHS/United States ; P30 EY021725/EY/NEI NIH HHS/United States ; R01 EY000871/EY/NEI NIH HHS/United States ; R01 EY030024/EY/NEI NIH HHS/United States ; },
abstract = {The postmitotic retina is highly metabolic and the photoreceptors depend on aerobic glycolysis for an energy source and cellular anabolic activities. Lactate dehydrogenase A (LDHA) is a key enzyme in aerobic glycolysis, which converts pyruvate to lactate. Here we show that cell-type-specific actively translating mRNA purification by translating ribosome affinity purification shows a predominant expression of LDHA in rods and cones and LDHB in the retinal pigment epithelium and Müller cells. We show that genetic ablation of LDHA in the retina resulted in diminished visual function, loss of structure, and a loss of dorsal-ventral patterning of the cone-opsin gradient. Loss of LDHA in the retina resulted in increased glucose availability, promoted oxidative phosphorylation, and upregulated the expression of glutamine synthetase (GS), a neuron survival factor. However, lacking LDHA in Müller cells does not affect visual function in mice. Glucose shortage is associated with retinal diseases, such as age-related macular degeneration (AMD), and regulating the levels of LDHA may have therapeutic relevance. These data demonstrate the unique and unexplored roles of LDHA in the maintenance of a healthy retina.},
}
@article {pmid36894043,
year = {2023},
author = {Guerra, MCA and Neto, JT and Gomes, MG and Dourado, LFN and Oréfice, RL and Heneine, LGD and Silva-Cunha, A and Fialho, SL},
title = {Nanofiber-coated implants: Development and safety after intravitreal application in rabbits.},
journal = {International journal of pharmaceutics},
volume = {636},
number = {},
pages = {122809},
doi = {10.1016/j.ijpharm.2023.122809},
pmid = {36894043},
issn = {1873-3476},
mesh = {Animals ; Rabbits ; Bevacizumab ; *Glucocorticoids ; Dexamethasone ; *Nanofibers ; Drug Implants ; Intravitreal Injections ; Angiogenesis Inhibitors ; Treatment Outcome ; },
abstract = {Intravitreal injections are the preferred choice for drug administration to the posterior segment of the eye. However, the required frequent injections may cause complications to the patient and low adherence to the treatment. Intravitreal implants are able to maintain therapeutic levels for a long period. Biodegradable nanofibers can modulate drug release and allow the incorporation of fragile bioactive drugs. Age-related macular degeneration is one of the world major causes of blindness and irreversible vision loss. It involves the interaction between VEGF and inflammatory cells. In this work we developed nanofiber-coated intravitreal implants containing dexamethasone and bevacizumab for simultaneously delivery of these drugs. The implant was successfully prepared and the efficiency of the coating process was confirmed by scanning electron microscopy. Around 68% of dexamethasone was released in 35 days and 88% of bevacizumab in 48hs. The formulation presented activity in the reduction of vessels and was safe to the retina. It was not observed any clinical or histopathological change, neither alteration in retina function or thickness by electroretinogram and optical coherence tomography during 28 days. The nanofiber-coated implants of dexamethasone and bevacizumab may be considered as a new delivery system that can be effective for the treatment of AMD.},
}
@article {pmid36893438,
year = {2023},
author = {Wykoff, CC and Matsumoto, H and Barakat, MR and Karcher, H and Lozama, A and Mayhook, A and Oshagbemi, OA and Zorina, O and Hassan, TS and Khanani, AM and Heier, JS},
title = {RETINAL VASCULITIS OR VASCULAR OCCLUSION AFTER BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Systematic Review of Real-World Evidence.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {7},
pages = {1051-1063},
pmid = {36893438},
issn = {1539-2864},
mesh = {Humans ; Male ; Female ; Aged, 80 and over ; *Retinal Vasculitis/chemically induced ; *Macular Degeneration/drug therapy ; *Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Aged ; },
abstract = {PURPOSE: Retinal vasculitis or vascular occlusion (RV/RO) have been reported after brolucizumab for neovascular age-related macular degeneration. This systematic literature review evaluated RV/RO events after brolucizumab in real-world practice.<br><br>METHODS: Systematic literature searches identified 89 publications; 19 were included.<br><br>RESULTS: Publications described 63 patients (70 eyes) with an RV/RO event following brolucizumab. Mean age was 77.6 years and 77.8% of patients were women; 32 eyes (45.7%) received one brolucizumab injection before RV/RO. Mean (range) time to event from last brolucizumab injection was 19.4 (0-63) days, with 87.5% of events occurring within 30 days. Among eyes with preevent and postevent visual acuity (VA) assessments, 22/42 eyes (52.4%) showed unchanged (&#xb1;0.08 logMAR) or improved vision from last recorded preevent assessment at latest follow-up, whereas 15/42 eyes (35.7%) showed &#x2265;0.30 logMAR (&#x2265;15 letters) VA reduction. Patients with no VA loss were on average slightly younger and had a higher proportion of nonocclusive events.<br><br>CONCLUSION: Most RV/RO events reported after brolucizumab in early real-world practice occurred in women. Among eyes with VA measurements, approximately half experienced VA loss; overall, about one-third had VA reduction of &#x2265;0.30 logMAR at latest follow-up, with indications of regional variations.},
}
@article {pmid36893432,
year = {2023},
author = {Cornish, EE and Nguyen, V and Puzo, M and O'Toole, L and Gemmy Cheung, CM and Vincent, A and Guillaumie, T and Oei, SL and Morros, HB and Barthelmes, D and Gillies, MC},
title = {OUTCOMES OF SWITCHING FROM PROACTIVE TO REACTIVE TREATMENT AFTER DEVELOPING ADVANCED CENTRAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {7},
pages = {1070-1080},
doi = {10.1097/IAE.0000000000003771},
pmid = {36893432},
issn = {1539-2864},
mesh = {Humans ; Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Visual Acuity ; Angiogenesis Inhibitors/therapeutic use ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Atrophy/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: We assessed outcomes of eyes with neovascular age-related macular degeneration (nAMD) that switched from proactive (treat-and-extend) to reactive (pro re nata) treatment regimen after developing macular atrophy (MA) or submacular fibrosis (SMFi).<br><br>METHODS: Data were collected from a retrospective analysis of a prospectively designed, multinational registry of "real-world" nAMD treatment outcomes. Eyes without MA or SMFi when starting treatment with a vascular endothelial growth factor inhibitor regimen that subsequently developed MA or SMFi were included.<br><br>RESULTS: Macular atrophy developed in 821 eyes and SMFi in 1,166 eyes. Seven percent of eyes that developed MA and 9% of those that developed SMFi were switched to reactive treatment. Vision was stable at 12 months for all eyes with MA and inactive SMFi. Active SMFi eyes that switched to reactive treatment had significant vision loss. No eyes that continued proactive treatment developed &#x2265;15 letter loss, but 8% of all eyes that switched to a reactive regimen and 15% of active SMFi eyes did.<br><br>CONCLUSION: Eyes that switch from proactive to reactive treatment after developing MA and inactive SMFi can have stable visual outcomes. Physicians should be aware of the risk of a significant loss of vision in eyes with active SMFi that switch to reactive treatment.},
}
@article {pmid36891017,
year = {2023},
author = {Monis, MD and Ali, SM and Bhutto, IA and Mahar, PS},
title = {Idiopathic Choroidal Neovascularization in Pregnancy: A Case Report.},
journal = {Cureus},
volume = {15},
number = {2},
pages = {e34611},
pmid = {36891017},
issn = {2168-8184},
abstract = {Choroidal neovascularization (CNV) is the abnormal growth of vessels from the choroidal vasculature to the neurosensory retina through the Bruch's membrane and is usually associated with "wet" age-related macular degeneration (AMD). Other causes include myopia, traumatic rupture of the choroid, multifocal choroiditis, and histoplasmosis. CNV is a major cause of visual loss and treatment is aimed at halting progression and stabilizing vision. Intravitreal anti-vascular endothelial growth factor (IVT anti-VEGF) injection is the treatment of choice for CNV regardless of etiology. However, its use in pregnancy is debatable, due to its mechanism of action and lack of evidence of safety in pregnancy. Herein, we report a 27-year-old pregnant female, who complained of blurred and decreased vision in her left eye for two weeks. On examination, her unaided vision was 6/6 in her right eye and 6/18 partial in her left eye with no further improvement. Based on history, examination, and investigations she was diagnosed as a case of idiopathic CNV in pregnancy, being only the sixth reported case worldwide. Citing the risk of possible fetal adverse effects, the patient did not consent to the treatment despite extensive counseling. She was advised to follow up regularly and to receive IVT anti-VEGF injections immediately after delivery. A literature review was therefore undertaken to broaden our understanding of the treatment protocols and outcomes of using IVT anti-VEGF in pregnancy. This helped us to develop an understanding of the possible relative safety of such a treatment when individually tailored with a multi-disciplinary approach.},
}
@article {pmid36888557,
year = {2023},
author = {Dos Santos, BB and Ribeiro Junior, MLB and Garcia, NP and Colombo Barboza, GN and Colombo Barboza, MN},
title = {OCT to identify macular changes not clinically detectable in elderly patients with cataract.},
journal = {Journal of cataract and refractive surgery},
volume = {49},
number = {7},
pages = {711-715},
doi = {10.1097/j.jcrs.0000000000001179},
pmid = {36888557},
issn = {1873-4502},
mesh = {Humans ; Aged ; Aged, 80 and over ; Tomography, Optical Coherence/methods ; Prospective Studies ; Cross-Sectional Studies ; Brazil ; *Cataract/diagnosis ; *Retinal Diseases ; },
abstract = {PURPOSE: To demonstrate the importance of optical coherence tomography (OCT) in identifying macular changes not detected at clinical examination preceding cataract surgery in patients older than 60 years.<br><br>SETTING: Hospital Oftalmol&#xf3;gico Vis&#xe3;o Laser, Santos, S&#xe3;o Paulo, Brazil.<br><br>DESING: Prospective case series.<br><br>METHODS: Patients older than 60 years were selected for this cross-sectional prospective study conducted during preoperative examination for cataract surgery. Eyes with a previous diagnosis or clinical evidence of macular disease or with media opacity preventing OCT from being performed were excluded from the study. All the study participants underwent OCT and were then divided into 2 groups: patients with macular changes and patients without macular changes found on OCT.<br><br>RESULTS: Of 364 eyes screened (212 patients), 300 eyes (180 patients) were included in the study. OCT identified macular changes in 40 eyes (13.3%), with age-related macular degeneration being found in 13 eyes (4.3%), epiretinal membrane in 12 eyes (4%), intraretinal fluid in 12 eyes (4%), and macular hole in 3 eyes (1%). In the group with macular changes, the mean age was 74.4 &#xb1; 6.3 years compared with 70.4 &#xb1; 6.7 years for those without changes (P < .001).<br><br>CONCLUSIONS: OCT proved an effective method for identifying macular diseases not detected at clinical evaluation before cataract surgery. Therefore, the relevance of performing OCT in these cases was confirmed and should be taken into consideration, particularly when evaluating patients older than 60 years.},
}
@article {pmid36884230,
year = {2023},
author = {Foster, MJ and Shaia, J and Maatouk, CM and Urbano, CA and Bui, MT and Hom, GL and Kuo, BL and Singh, RP and Talcott, KE},
title = {Long-Term Visual Outcomes in Neovascular Age-Related Macular Degeneration Eyes With Baseline Macular Atrophy on Anti-Vascular Endothelial Growth Factor Treatment.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {4},
pages = {223-230},
doi = {10.3928/23258160-20230223-01},
pmid = {36884230},
issn = {2325-8179},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Endothelial Growth Factors/therapeutic use ; Retrospective Studies ; *Macular Degeneration/drug therapy ; Atrophy/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {BACKGROUND AND OBJECTIVE: This study explores the connection between macular atrophy (MA) status at baseline and best visual acuity (BVA) after 5 to 7 years of anti-vascular endothelial growth factor (anti-VEGF) injections on eyes with neovascular age-related macular degeneration (nAMD).<br><br>PATIENTS AND METHODS: This retrospective study included patients with neovascular age-related macular degeneration receiving anti-VEGF injections at least twice-yearly for 5+ years at Cole Eye Institute. Analyses of variance and linear regressions explored the connection between MA status, baseline MA intensity, and 5-year BVA change.<br><br>RESULTS: Of 223 included patients, 5-year BVA change was not statistically significant between MA status groups or from baseline. The population's average 7-year BVA change was -6.3 Early Treatment Diabetic Retinopathy Study letters. Type and frequency of anti-VEGF injections were comparable between MA status groups (P > 0.05).<br><br>CONCLUSION: Regardless of MA status, 5- and 7-year BVA change lacked clinical relevance. If receiving regular treatment for 5+ years, patients with baseline MA achieve comparable visual outcomes to those without MA, with similar treatment and visit burdens. [Ophthalmic Surg Lasers Imaging Retina 2023;54:223-230.].},
}
@article {pmid36884066,
year = {2023},
author = {Pauleikhoff, L and Rothaus, K and Groß-Bölting, F and Böhringer, D and Lübke, J and Agostini, H and Lange, C and , },
title = {[Photodynamic therapy in Germany-Quo vadis?].},
journal = {Die Ophthalmologie},
volume = {120},
number = {8},
pages = {818-824},
pmid = {36884066},
issn = {2731-7218},
support = {PA 4282/1-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {Humans ; Photosensitizing Agents/therapeutic use ; *Photochemotherapy/adverse effects ; Retrospective Studies ; Verteporfin/therapeutic use ; *Choroidal Neovascularization/drug therapy ; *Choroid Neoplasms/complications ; },
abstract = {BACKGROUND: Photodynamic therapy (PDT) was originally approved for the treatment of neovascular age-related macular degeneration (nAMD) and secondary choroidal neovascularization in myopia (mCNV). In addition, it is used as an off-label treatment in patients with choroidal hemangioma, polypoidal choroidal vasculopathy (PCV), and central serous chorioretinopathy (CSC).<br><br>OBJECTIVE: To track the development of PDT treatment numbers in Germany between 2006 and 2021 and to investigate the composition of the therapeutic indications.<br><br>METHODS: In this retrospective study the quality reports of German hospitals were evaluated in the period from 2006 to 2019 and the number of PDTs performed was recorded. In addition, the range of indications for PDT was determined exemplarily for the Eye Center at Medical Center, University of Freiburg and the Eye Center at St. Franziskus Hospital in M&#xfc;nster between 2006 and 2021. Finally, the estimated prevalence of CSC and an estimate of cases requiring treatment were used to calculate the number of patients in need of PDT treatment in Germany.<br><br>RESULTS: The number of PDTs performed in Germany decreased from 1072 in 2006 to 202 in 2019. While PDT was used in 86% of cases in patients with nAMD and in 7% of cases with mCNV in 2006, it was mainly performed in patients with CSC (70%) and choroidal hemangiomas (21%) from 2016 to 2021. With an estimated incidence of CSC of 1:10,000 and assuming that 16% of patients develop chronic CCS requiring treatment, approximately 1330 PDTs would need to be performed per year in Germany for patients with newly diagnosed chronic CSC alone.<br><br>CONCLUSION: The decreasing numbers of PDT treatment performed in Germany is mainly due to a&#xa0;change to intravitreal injections as the preferred treatment for nAMD and mCNV. As PDT is currently the recommended treatment of choice for chronic CSC, an underprovision of PDT in Germany can be assumed. To enable an appropriate treatment for patients, a&#xa0;reliable verteporfin production, a&#xa0;simplified approval process by health insurance companies and a&#xa0;close cooperation between ophthalmologists in private practice and larger centers are urgently needed.},
}
@article {pmid36882871,
year = {2023},
author = {Todorova, V and Stauffacher, MF and Ravotto, L and Nötzli, S and Karademir, D and Ebner, LJA and Imsand, C and Merolla, L and Hauck, SM and Samardzija, M and Saab, AS and Barros, LF and Weber, B and Grimm, C},
title = {Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation.},
journal = {Molecular neurodegeneration},
volume = {18},
number = {1},
pages = {15},
pmid = {36882871},
issn = {1750-1326},
mesh = {Humans ; *Oxidative Phosphorylation ; *Retinal Degeneration ; Glucose ; Hypoxia ; Lactic Acid ; Retinal Rod Photoreceptor Cells ; },
abstract = {BACKGROUND: Major retinal degenerative diseases, including age-related macular degeneration, diabetic retinopathy and retinal detachment, are associated with a local decrease in oxygen availability causing the formation of hypoxic areas affecting the photoreceptor (PR) cells. Here, we addressed the underlying pathological mechanisms of PR degeneration by focusing on energy metabolism during chronic activation of hypoxia-inducible factors (HIFs) in rod PR.<br><br>METHODS: We used two-photon laser scanning microscopy (TPLSM) of genetically encoded biosensors delivered by adeno-associated viruses (AAV) to determine lactate and glucose dynamics in PR and inner retinal cells. Retinal layer-specific proteomics, in situ enzymatic assays and immunofluorescence studies were used to analyse mitochondrial metabolism in rod PRs during chronic HIF activation.<br><br>RESULTS: PRs exhibited remarkably higher glycolytic flux through the hexokinases than neurons of the inner retina. Chronic HIF activation in rods did not cause overt change in glucose dynamics but an increase in lactate production nonetheless. Furthermore, dysregulation of the oxidative phosphorylation pathway (OXPHOS) and tricarboxylic acid (TCA) cycle in rods with an activated hypoxic response decelerated cellular anabolism causing shortening of rod photoreceptor outer segments (OS) before onset of cell degeneration. Interestingly, rods with deficient OXPHOS but an intact TCA cycle did not exhibit these early signs of anabolic dysregulation and showed a slower course of degeneration.<br><br>CONCLUSION: Together, these data indicate an exceeding high glycolytic flux in rods and highlight the importance of mitochondrial metabolism and especially of the TCA cycle for PR survival in conditions of increased HIF activity.},
}
@article {pmid36882530,
year = {2023},
author = {Thottarath, S and Chandra, S and Gurudas, S and Tsai, WS and Giani, A and De Cock, E and Yamaguchi, TCN and Sivaprasad, S and , },
title = {Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON).},
journal = {Eye (London, England)},
volume = {37},
number = {14},
pages = {3004-3008},
pmid = {36882530},
issn = {1476-5454},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Neon/therapeutic use ; Prevalence ; State Medicine ; Vascular Endothelial Growth Factor A/therapeutic use ; Fluorescein Angiography/methods ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy/epidemiology ; *Choroidal Neovascularization/diagnosis/drug therapy/epidemiology ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Multicenter Studies as Topic ; },
abstract = {PURPOSE: Fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD.<br><br>METHODS: EYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed.<br><br>CONCLUSION: The study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD.},
}
@article {pmid36882430,
year = {2023},
author = {Garzone, D and Terheyden, JH and Morelle, O and Wintergerst, MWM and Saßmannshausen, M and Schmitz-Valckenberg, S and Pfau, M and Thiele, S and Poor, S and Leal, S and Holz, FG and Finger, RP and , },
title = {Author Correction: Comparability of automated drusen volume measurements in age-related macular degeneration: a MACUSTAR study report.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {3795},
doi = {10.1038/s41598-023-30360-1},
pmid = {36882430},
issn = {2045-2322},
}
@article {pmid36881917,
year = {2022},
author = {Pinelli, R and Biagioni, F and Scaffidi, E and Vakunseth Bumah, V and Busceti, CL and Puglisi-Allegra, S and Lazzeri, G and Fornai, F},
title = {The potential effects of nutrients and light on autophagy-mediated visual function and clearance of retinal aggregates.},
journal = {Archives italiennes de biologie},
volume = {160},
number = {3-4},
pages = {115-135},
doi = {10.12871/000398292022345},
pmid = {36881917},
issn = {0003-9829},
mesh = {Humans ; *Retinal Degeneration ; Retina ; Nutrients ; Retinal Pigment Epithelium ; Autophagy ; },
abstract = {Increasing findings indicate that a dysfunction in the autophagy machinery is common during retinal degeneration. The present article provides evidence showing that an autophagy defect in the outer retinal layers is commonly described at the onset of retinal degeneration. These findings involve a number of structures placed at the border between the inner choroid and the outer retina encompassing the choriocapillaris, the Bruch's membrane, photoreceptors and Mueller cells. At the center of these anatomical substrates are placed cells forming the retinal pigment epithelium (RPE), where autophagy seems to play most of its effects. In fact, a failure of the autophagy flux is mostly severe at the level of RPE. Among various retinal degenerative disorders, age-related macular degeneration (AMD) is mostly affected by a damage to RPE, which can be reproduced by inhibiting the autophagy machinery and it can be counteracted by the activation of the autophagy pathway. In the present manuscript evidence is provided that such a severe impairment of retinal autophagy may be counteracted by administration of a number of phytochemicals, which possess a strong stimulatory activity on autophagy. Likewise, natural light stimulation administered in the form of pulsatile specific wavelengths is capable of inducing autophagy within the retina. This dual approach to stimulate autophagy is further strengthened by the interaction of light with phytochemicals which is shown to activate the chemical properties of these natural molecules in sustaining retinal integrity. The beneficial effects of photo-biomodulation combined with phytochemicals is based on the removal of toxic lipid, sugar and protein species along with the stimulation of mitochondrial turn-over. Additional effects of autophagy stimulation under the combined effects of nutraceuticals and light pulses are discussed concerning stimulation of retinal stem cells which partly correspond to a subpopulation of RPE cells.},
}
@article {pmid36880020,
year = {2023},
author = {Mehta, N and Fong, RD and Wilson, M and Moussa, K and Emami-Naeini, P and Moshiri, A and Yiu, G and Park, SS},
title = {Real-World Experience Using Intravitreal Brolucizumab Alone or in Combination with Aflibercept in the Management of Neovascular Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {657-665},
pmid = {36880020},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate real-world experience using intravitreal brolucizumab (IVBr), alone or in combination with aflibercept, in eyes with neovascular age-related macular degeneration (nAMD) treated previously with other inhibitors of VEGF (anti-VEGF).<br><br>METHODS: This was a retrospective study of all eyes with nAMD treated with IVBr on a treat-and-extend protocol at a single center. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) at baseline and final visit, and drug-related adverse events were analyzed. Eyes with recurrent macular fluid on IVBr every 8 weeks were treated with a combination therapy alternating between IVBr and aflibercept every month.<br><br>RESULTS: Among 52 eyes (40 patients) on IVBr, all had been previously treated with other anti-VEGF therapy, with 73% having persistent macular fluid. After a mean follow-up of 46.2&#xb1;27.4 weeks on IVBr, the mean treatment interval for intravitreal therapy increased to 8.8&#xb1;2.1 weeks on IVBr from a baseline of 6.1&#xb1;3.1 weeks (p<0.001). Macular fluid decreased and BCVA was stable/improved in 61.5% of eyes on IVBr. Ten eyes with increased macular fluid on IVBr monotherapy when extended to every 8 weeks were treated with combination therapy alternating between IVBr and aflibercept every 4 weeks. In these eyes, 80% had improved macular fluid on OCT and 70% stable or improved BCVA after a median follow-up of 53 weeks on combination therapy. Mild intraocular inflammation developed in four eyes, all occurring on IVBr monotherapy, and none had associated vision loss.<br><br>CONCLUSION: In the real world, IVBr used to treat eyes with nAMD previously treated with other anti-VEGF therapies appears to be well tolerated and associated with an improvement in macular fluid, stabilization of BCVA, and/or increase in intravitreal treatment interval. Combination therapy alternating between IVBr and aflibercept monthly appears to be well tolerated and can be considered for eyes with macular fluid on IVBr every 8 weeks.},
}
@article {pmid36879074,
year = {2023},
author = {Sawada, T and Yasukawa, T and Imaizumi, H and Matsubara, H and Kimura, K and Terasaki, H and Ishikawa, H and Murakami, T and Takeuchi, M and Mitamura, Y and Mizusawa, Y and Takamura, Y and Murata, T and Kogo, J and Ohji, M},
title = {Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {2},
pages = {149-155},
pmid = {36879074},
issn = {1613-2246},
mesh = {Humans ; East Asian People ; Fluorescein Angiography ; Follow-Up Studies ; Intravitreal Injections ; *Macular Degeneration/diagnosis/epidemiology/drug therapy ; Prevalence ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/epidemiology ; Middle Aged ; Aged ; Aged, 80 and over ; },
abstract = {PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD).<br><br>STUDY DESIGN: Retrospective multicenter case series.<br><br>METHODS: We reviewed the records of patients with treatment-na&#xef;ve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis.<br><br>RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P&#x2009;< 0.001).<br><br>CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.},
}
@article {pmid36878916,
year = {2023},
author = {Park, J and Cui, G and Lee, H and Jeong, H and Kwak, JJ and Lee, J and Byeon, SH},
title = {CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {3715},
pmid = {36878916},
issn = {2045-2322},
mesh = {Humans ; Animals ; Mice ; Retinal Pigment Epithelium ; CRISPR-Cas Systems ; *Choroidal Neovascularization/genetics/therapy ; Retina ; *Craniocerebral Trauma ; Disease Models, Animal ; Vascular Endothelial Growth Factor A/genetics ; },
abstract = {The CRISPR/Cas9 system easily edits target genes in various organisms and is used to treat human diseases. In most therapeutic CRISPR studies, ubiquitously expressed promoters, such as CMV, CAG, and EF1α, are used; however, gene editing is sometimes necessary only in specific cell types relevant to the disease. Therefore, we aimed to develop a retinal pigment epithelium (RPE)-specific CRISPR/Cas9 system. We developed a CRISPR/Cas9 system that operates only in retinal pigment epithelium (RPE) by expressing Cas9 under the RPE-specific vitelliform macular dystrophy 2 promoter (pVMD2). This RPE-specific CRISPR/pVMD2-Cas9 system was tested in human retinal organoid and mouse model. We confirmed that this system works specifically in the RPE of human retinal organoids and mouse retina. In addition, the RPE-specific Vegfa ablation using the novel CRISPR-pVMD2-Cas9 system caused regression of choroidal neovascularization (CNV) without unwanted knock-out in the neural retina in laser-induced CNV mice, which is a widely used animal model of neovascular age-related macular degeneration. RPE-specific Vegfa knock-out (KO) and ubiquitous Vegfa KO were comparable in the efficient regression of CNV. The promoter substituted, cell type-specific CRISPR/Cas9 systems can be used in specific 'target cell' therapy, which edits genes while reducing unwanted off- 'target cell' effects.},
}
@article {pmid36877299,
year = {2023},
author = {Lee, JH and Ahn, J and Shin, JY},
title = {Sequential structural and functional change in geographic atrophy on multimodal imaging in non-exudative age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {8},
pages = {2199-2207},
pmid = {36877299},
issn = {1435-702X},
mesh = {Humans ; Middle Aged ; Aged ; Aged, 80 and over ; *Geographic Atrophy ; Retinal Pigment Epithelium/pathology ; Retina/pathology ; Tomography, Optical Coherence/methods ; Multimodal Imaging ; Atrophy ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To investigate the temporal order of photoreceptor atrophy, retinal pigment epithelium (RPE) atrophy and visual acuity loss in patients with center-involving geographic atrophy (GA) in non-exudative age-related macular degeneration (neAMD).<br><br>METHODS: Forty eyes of 25 consecutive patients who eventually developed center-involving GA were investigated. Fundus autofluorescence (FAF) and infrared image coupled optical coherence tomography (OCT) were acquired at each visit. Development of RPE atrophy and photoreceptor atrophy was defined as abnormal hyper/hypo-fluorescence on FAF and photoreceptor loss on OCT over 50% of the vertical or horizontal diameters of the center 1&#xa0;mm circle, respectively. Visual acuity loss was defined as worsening of more than 0.2 logMAR compared to baseline. Kaplan-Meier analyses was performed to compare the sequential order of these three events.<br><br>RESULTS: Mean age was 72.72&#x2009;&#xb1;&#x2009;8.63&#xa0;years, and follow-up duration was 27.36&#x2009;&#xb1;&#x2009;17.22&#xa0;months, with an average number of visits of 3.04&#x2009;&#xb1;&#x2009;1.54 during follow-up. GA progressed from photoreceptor atrophy on OCT, RPE atrophy on FAF, and then to vision loss (p&#x2009;<&#x2009;0.001). The median survival time of photoreceptors preceded that of visual acuity by 16.3&#xa0;months, and the median survival time of RPE preceded that of visual acuity by 7.0&#xa0;months. At baseline, majority of eyes showed drusen only (57.5%), while the most common feature was incomplete RPE and outer retinal atrophy at 3-year follow-up (40.4%).<br><br>CONCLUSION: In the progression of center-involving GA, photoreceptor atrophy on OCT and RPE atrophy on FAF precedes visual decline, and can act as biomarkers predicting future visual decline within the following years.},
}
@article {pmid36876510,
year = {2023},
author = {Holtz, JK and Thinggaard, BS and Grauslund, J and Subhi, Y},
title = {Association between oral metformin use and the risk of age-related macular degeneration: A systematic review with meta-analysis.},
journal = {Acta ophthalmologica},
volume = {101},
number = {6},
pages = {595-605},
doi = {10.1111/aos.15655},
pmid = {36876510},
issn = {1755-3768},
mesh = {Humans ; *Metformin ; *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology ; *Macular Degeneration/epidemiology/complications ; },
abstract = {Rodent studies demonstrate that oral metformin use may reduce chronic low-grade inflammation, downregulate apoptosis and extend life span. Emerging epidemiological evidence suggests that oral metformin use may protect against development of age-related macular degeneration (AMD) in humans. In this study, we systematically reviewed the literature on the association between oral metformin use and AMD in patients with type 2 diabetes and conducted a quantitative meta-analysis to provide a summary estimate of the association. We searched 12 literature databases on 10 August 2022 and identified nine eligible studies with data on a total of 1 427 074 individuals with diabetes. We found that patients with diabetes using metformin had a significantly lower odds ratio (OR) of having or developing AMD (OR 0.63; 95% CI: 0.46-0.86; p = 0.004). Our analyses also revealed that although the findings were robust in the sensitivity analysis, the Funnel plot indicated a certain publication bias towards finding a protective effect. Results of individual studies suggested inconsistent findings, as some studies found lower risk of AMD from higher total metformin exposure, whereas other studies found a higher risk of AMD from higher total metformin exposure. Taken together, there may be a link between metformin use and lower risk of AMD, but the relationship is only studied in observational studies, various sources of bias can be speculated to influence, and careful interpretation is warranted.},
}
@article {pmid36876427,
year = {2023},
author = {Miller, A and Crossland, MD and Macnaughton, J and Latham, K},
title = {Are wearable electronic vision enhancement systems (wEVES) beneficial for people with age-related macular degeneration? A scoping review.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {43},
number = {4},
pages = {680-701},
doi = {10.1111/opo.13117},
pmid = {36876427},
issn = {1475-1313},
mesh = {Humans ; Quality of Life ; *Vision, Low/etiology ; *Macular Degeneration/therapy/complications ; Activities of Daily Living ; *Wearable Electronic Devices ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the United Kingdom. It has a wide-ranging detrimental impact on daily living, including impairment of functional ability and quality of life. Assistive technology designed to overcome this impairment includes wearable electronic vision enhancement systems (wEVES). This scoping review assesses the usefulness of these systems for people with AMD.<br><br>METHODS: Four databases (Cumulative Index to Nursing and Allied Health Literature, PubMed, Web of Science and Cochrane CENTRAL) were searched to identify papers that investigated image enhancement with a head-mounted electronic device on a sample population that included people with AMD.<br><br>RESULTS: Thirty-two papers were included: 18 studied the clinical and functional benefits of wEVES, 11 investigated use and usability and 3 discussed sickness and adverse effects.<br><br>CONCLUSIONS: Wearable electronic vision enhancement systems provide hands-free magnification and image enhancement producing significant improvements in acuity, contrast sensitivity and aspects of laboratory-simulated daily activity. Adverse effects were infrequent, minor and spontaneously resolved with the removal of the device. However, when symptoms arose, they sometimes persisted with continued device usage. There are multi-factorial influences and a diversity of user opinions on promotors to successful device use. These factors are not exclusively driven by visual improvement and incorporate other issues including device weight, ease of use and inconspicuous design. There is insufficient evidence of any cost-benefit analysis for wEVES. However, it has been shown that a user's decision to make a purchase evolves over time, with their estimates of cost falling below the retail price of the devices. Additional research is needed to understand the specific and distinct benefits of wEVES for people with AMD. Further patient-centred research should assess the benefits of wEVES in user-led activities when directly compared with alternative coping strategies, allowing professionals and users to make better prescribing and purchasing decisions.},
}
@article {pmid36875760,
year = {2023},
author = {Zhang, Z and Wang, Y and Zhang, H and Samusak, A and Rao, H and Xiao, C and Abula, M and Cao, Q and Dai, Q},
title = {Artificial intelligence-assisted diagnosis of ocular surface diseases.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1133680},
pmid = {36875760},
issn = {2296-634X},
abstract = {With the rapid development of computer technology, the application of artificial intelligence (AI) in ophthalmology research has gained prominence in modern medicine. Artificial intelligence-related research in ophthalmology previously focused on the screening and diagnosis of fundus diseases, particularly diabetic retinopathy, age-related macular degeneration, and glaucoma. Since fundus images are relatively fixed, their standards are easy to unify. Artificial intelligence research related to ocular surface diseases has also increased. The main issue with research on ocular surface diseases is that the images involved are complex, with many modalities. Therefore, this review aims to summarize current artificial intelligence research and technologies used to diagnose ocular surface diseases such as pterygium, keratoconus, infectious keratitis, and dry eye to identify mature artificial intelligence models that are suitable for research of ocular surface diseases and potential algorithms that may be used in the future.},
}
@article {pmid36875335,
year = {2023},
author = {Owsley, C and Swain, TA and McGwin, G and Clark, ME and Kar, D and Curcio, CA},
title = {Biologically Guided Optimization of Test Target Location for Rod-mediated Dark Adaptation in Age-related Macular Degeneration: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.},
journal = {Ophthalmology science},
volume = {3},
number = {2},
pages = {100274},
pmid = {36875335},
issn = {2666-9145},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: We evaluate the impact of test target location in assessing rod-mediated dark adaptation (RMDA) along the transition from normal aging to intermediate age-related macular degeneration (AMD). We consider whether RMDA slows because the test locations are near mechanisms leading to or resulting from high-risk extracellular deposits. Soft drusen cluster under the fovea and extend to the inner ring of the ETDRS grid where rods are sparse. Subretinal drusenoid deposits (SDDs) appear first in the outer superior subfield of the ETDRS grid where rod photoreceptors are maximal and spread toward the fovea without covering it.<br><br>DESIGN: Cross-sectional.<br><br>PARTICIPANTS: Adults &#x2265; 60 years with normal older maculas, early AMD, or intermediate AMD as defined by the Age-Related Eye Disease Study (AREDS) 9-step and Beckman grading systems.<br><br>METHODS: In 1 eye per participant, RMDA was assessed at 5&#xb0; and at 12&#xb0; in the superior retina. Subretinal drusenoid deposit presence was identified with multi-modal imaging.<br><br>MAIN OUTCOME MEASURES: Rod intercept time (RIT) as a measure of RMDA rate at 5&#xb0; and 12&#xb0;.<br><br>RESULTS: In 438 eyes of 438 persons, RIT was significantly longer (i.e., RMDA is slower) at 5&#xb0; than at 12&#xb0; for each AMD severity group. Differences among groups were bigger at 5&#xb0; than at 12&#xb0;. At 5&#xb0;, SDD presence was associated with longer RIT as compared to SDD absence at early and intermediate AMD but not in normal eyes. At 12&#xb0;, SDD presence was associated with longer RIT in intermediate AMD only, and not in normal or early AMD eyes. Findings were similar in eyes stratified by AREDS 9-step and Beckman systems.<br><br>CONCLUSIONS: We probed RMDA in relation to current models of deposit-driven AMD progression organized around photoreceptor topography. In eyes with SDD, slowed RMDA occurs at 5&#xb0; where these deposits typically do not appear until later in AMD. Even in eyes lacking detectable SDD, RMDA at 5&#xb0; is slower than at 12&#xb0;. The effect at 5&#xb0; may be attributed to mechanisms associated with the accumulation of soft drusen and precursors under the macula lutea throughout adulthood. These data will facilitate the design of efficient clinical trials for interventions that aim to delay AMD progression.},
}
@article {pmid36875133,
year = {2023},
author = {Santos, FM and Ciordia, S and Mesquita, J and Cruz, C and Sousa, JPCE and Passarinha, LA and Tomaz, CT and Paradela, A},
title = {Proteomics profiling of vitreous humor reveals complement and coagulation components, adhesion factors, and neurodegeneration markers as discriminatory biomarkers of vitreoretinal eye diseases.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1107295},
pmid = {36875133},
issn = {1664-3224},
mesh = {Humans ; Vitreous Body ; Angiogenesis Inhibitors ; Proteomics ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Complement System Proteins ; Biomarkers ; *Diabetic Retinopathy ; *Epiretinal Membrane ; },
abstract = {INTRODUCTION: Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD.<br><br>METHODS: To unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4).<br><br>RESULTS AND DISCUSSION: Post-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. Pathway analysis indicates that mediators of complement, coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and monitored by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins could differentiate between these vitreoretinal diseases. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (complement C2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).},
}
@article {pmid36875027,
year = {2023},
author = {Pan, Y and Liu, J and Cai, Y and Yang, X and Zhang, Z and Long, H and Zhao, K and Yu, X and Zeng, C and Duan, J and Xiao, P and Li, J and Cai, F and Yang, X and Tan, Z},
title = {Fundus image classification using Inception V3 and ResNet-50 for the early diagnostics of fundus diseases.},
journal = {Frontiers in physiology},
volume = {14},
number = {},
pages = {1126780},
pmid = {36875027},
issn = {1664-042X},
abstract = {Purpose: We aim to present effective and computer aided diagnostics in the field of ophthalmology and improve eye health. This study aims to create an automated deep learning based system for categorizing fundus images into three classes: normal, macular degeneration and tessellated fundus for the timely recognition and treatment of diabetic retinopathy and other diseases. Methods: A total of 1,032 fundus images were collected from 516 patients using fundus camera from Health Management Center, Shenzhen University General Hospital Shenzhen University, Shenzhen 518055, Guangdong, China. Then, Inception V3 and ResNet-50 deep learning models are used to classify fundus images into three classes, Normal, Macular degeneration and tessellated fundus for the timely recognition and treatment of fundus diseases. Results: The experimental results show that the effect of model recognition is the best when the Adam is used as optimizer method, the number of iterations is 150, and 0.00 as the learning rate. According to our proposed approach we, achieved the highest accuracy of 93.81% and 91.76% by using ResNet-50 and Inception V3 after fine-tuned and adjusted hyper parameters according to our classification problem. Conclusion: Our research provides a reference to the clinical diagnosis or screening for diabetic retinopathy and other eye diseases. Our suggested computer aided diagnostics framework will prevent incorrect diagnoses caused by the low image quality and individual experience, and other factors. In future implementations, the ophthalmologists can implement more advanced learning algorithms to improve the accuracy of diagnosis.},
}
@article {pmid36872752,
year = {2023},
author = {Shah, C and Sonkusare, K},
title = {Response to commentary on: A prospective, randomized, parallel group, double blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin's ranibizumab with Lucentis in patients with neovascular age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {3},
pages = {1054-1055},
pmid = {36872752},
issn = {1998-3689},
mesh = {Humans ; Double-Blind Method ; *Macular Degeneration ; Prospective Studies ; *Ranibizumab ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; },
}
@article {pmid36872680,
year = {2023},
author = {Joshi, RS and Doble, P},
title = {The complication rate following Neodymium-doped Yttrium Aluminum Garnet laser posterior capsulotomy for posterior capsular opacification in patients with and without comorbidities.},
journal = {Indian journal of ophthalmology},
volume = {71},
number = {3},
pages = {791-796},
pmid = {36872680},
issn = {1998-3689},
mesh = {Male ; Humans ; Female ; Middle Aged ; Aged ; *Lasers, Solid-State ; Posterior Capsulotomy ; Prospective Studies ; Eye ; *Laser Therapy ; },
abstract = {PURPOSE: To study the complication rate following Nd: YAG posterior capsulotomy posterior capsular opacification (PCO) in patients with and without comorbid conditions.<br><br>METHODS: This was a prospective, interventional, comparative, and observational study. A total of 80 eyes, consisting of 40 eyes without ocular comorbidities (group A) and 40 eyes with ocular comorbidities (group B) that were being treated with Nd: YAG capsulotomy for PCO, were included. Visual outcome and complications of Nd: YAG capsulotomy were studied.<br><br>RESULTS: The mean age of group A patients was 61.65 &#xb1; 8.85 years and that of group B patients was 63 &#xb1; 10.46 years. Of the total, 38 (47.5%) were men and 42 (52.5%) were women. In group B, the ocular comorbidities were moderate nonproliferative diabetic retinopathy (NPDR) (n = 14 eyes; 14/40 = 35%), subluxated intraocular lens (IOL; <2 clock hours of subluxation; n = 6), age-related macular degeneration (ARMD; n = 6), post-uveitic eyes (having old signs of uveitis, no episode of uveitis since the last 1 year; n = 5), and operated cases of traumatic cataract (n = 4). The mean energy required in groups A and B was 46.95 &#xb1; 25.92 and 42.62 &#xb1; 21.85 mJ, respectively (P = 0.422). The average energy requirement in Grade 2, Grade 3, and Grade 4 PCO was 22.30, 41.62, and 79.52 mJ, respectively. An increase in intraocular pressure (IOP) of >5 mmHg from pre-YAG levels was observed in one patient in each group on day 1 postprocedure, for which medical treatment was given to both patients for 7 days. One patient in each group had IOL pitting. No patient had any other complications attributable to ND:YAG capsulotomy.<br><br>CONCLUSION: Nd:YAG laser posterior capsulotomy is a safe procedure for PCO in patients with comorbidities. Visual outcomes were excellent after Nd:YAG posterior capsulotomy. Although a transient increase in IOP was noted, the response to treatment was good and a long-term increase in IOP was not observed.},
}
@article {pmid36871144,
year = {2023},
author = {Huang, K and Liu, X and Lv, Z and Zhang, D and Zhou, Y and Lin, Z and Guo, J},
title = {MMP9-Responsive Graphene Oxide Quantum Dot-Based Nano-in-Micro Drug Delivery System for Combinatorial Therapy of Choroidal Neovascularization.},
journal = {Small (Weinheim an der Bergstrasse, Germany)},
volume = {19},
number = {39},
pages = {e2207335},
doi = {10.1002/smll.202207335},
pmid = {36871144},
issn = {1613-6829},
mesh = {Humans ; Mice ; Animals ; Aged ; Matrix Metalloproteinase 9/therapeutic use ; Minocycline/therapeutic use ; *Quantum Dots ; Vascular Endothelial Growth Factor A ; *Choroidal Neovascularization/drug therapy/metabolism/pathology ; Drug Delivery Systems ; Angiogenesis Inhibitors/therapeutic use ; Inflammation/drug therapy ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {Age-related macular degeneration (AMD), especially wet AMD with choroidal neovascularization (CNV), commonly causes blindness in older patients and disruption of the choroid followed by second-wave injuries, including chronic inflammation, oxidative stress, and excessive matrix metalloproteinase 9 (MMP9) expression. Increased macrophage infiltrate in parallel with microglial activation and MMP9 overexpression on CNV lesions is shown to contribute to the inflammatory process and then enhance pathological ocular angiogenesis. Graphene oxide quantum dots (GOQDs), as natural antioxidants, exert anti-inflammatory effects and minocycline is a specific macrophage/microglial inhibitor that can suppress both macrophage/microglial activation and MMP9 activity. Herein, an MMP9-responsive GOQD-based minocycline-loaded nano-in-micro drug delivery system (C18PGM) is developed by chemically bonding GOQDs to an octadecyl-modified peptide sequence (C18-GVFHQTVS, C18P) that can be specifically cleaved by MMP9. Using a laser-induced CNV mouse model, the prepared C18PGM shows significant MMP9 inhibitory activity and anti-inflammatory action followed by antiangiogenic effects. Moreover, C18PGM combined with antivascular endothelial growth factor antibody bevacizumab markedly increases the antiangiogenesis effect by interfering with the "inflammation-MMP9-angiogenesis" cascade. The prepared C18PGM shows a good safety profile and no obvious ophthalmic or systemic side effects. The results taken together suggest that C18PGM is an effective and novel strategy for combinatorial therapy of CNV.},
}
@article {pmid36870451,
year = {2023},
author = {Regillo, C and Berger, B and Brooks, L and Clark, WL and Mittra, R and Wykoff, CC and Callaway, NF and DeGraaf, S and Ding, HT and Fung, AE and Gune, S and Le Pogam, S and Smith, R and Willis, JR and Barteselli, G},
title = {Archway Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration 2-Year Results.},
journal = {Ophthalmology},
volume = {130},
number = {7},
pages = {735-747},
doi = {10.1016/j.ophtha.2023.02.024},
pmid = {36870451},
issn = {1549-4713},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors ; Visual Acuity ; *Diabetic Retinopathy/drug therapy ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy/chemically induced ; },
abstract = {PURPOSE: To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Phase 3, randomized, multicenter, open-label, active-comparator-controlled trial.<br><br>PARTICIPANTS: Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy.<br><br>METHODS: Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (&#x223c;2 years).<br><br>MAIN OUTCOME MEASURES: Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 44 and 48, weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters).<br><br>RESULTS: The PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 44/48, 60/64 and 88/92 of&#xa0;-0.2 (95% confidence interval [CI], -1.8 to +1.3), +0.4 (95% CI, -1.4 to&#xa0;+2.1) and -0.6 ETDRS letters (95% CI, -2.5 to&#xa0;+1.3), respectively. Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. The PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events of special interest (AESI) were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. The most common AESI reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab.<br><br>CONCLUSIONS: The PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. The AESIs were generally manageable, with learnings continually implemented to minimize PDS-related AEs.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36870288,
year = {2023},
author = {Kakihara, S and Matsuda, Y and Hirabayashi, K and Imai, A and Iesato, Y and Sakurai, T and Kamiyoshi, A and Tanaka, M and Ichikawa-Shindo, Y and Kawate, H and Zhao, Y and Zhang, Y and Guo, Q and Li, P and Onishi, N and Murata, T and Shindo, T},
title = {Role of Adrenomedullin 2/Intermedin in the Pathogenesis of Neovascular Age-Related Macular Degeneration.},
journal = {Laboratory investigation; a journal of technical methods and pathology},
volume = {103},
number = {4},
pages = {100038},
doi = {10.1016/j.labinv.2022.100038},
pmid = {36870288},
issn = {1530-0307},
mesh = {Humans ; Mice ; Animals ; Adrenomedullin/genetics/pharmacology/therapeutic use ; Endothelial Cells/metabolism ; *Choroidal Neovascularization/genetics/drug therapy ; *Macular Degeneration/genetics/metabolism/pathology ; Inflammation/pathology ; Fibrosis ; *Neuropeptides/therapeutic use ; },
abstract = {Adrenomedullin 2 (AM2; also known as intermedin) is a member of the adrenomedullin (AM) peptide family. Similarly to AM, AM2 partakes in a variety of physiological activities. AM2 has been reported to exert protective effects on various organ disorders; however, its significance in the eye is unknown. We investigated the role of AM2 in ocular diseases. The receptor system of AM2 was expressed more abundantly in the choroid than in the retina. In an oxygen-induced retinopathy model, physiological and pathologic retinal angiogenesis did not differ between AM2-knockout (AM2-/-) and wild-type mice. In contrast, in laser-induced choroidal neovascularization, a model of neovascular age-related macular degeneration, AM2-/- mice had enlarged and leakier choroidal neovascularization lesions, with exacerbated subretinal fibrosis and macrophage infiltration. Contrary to this, exogenous administration of AM2 ameliorated the laser-induced choroidal neovascularization-associated pathology and suppressed gene expression associated with inflammation, fibrosis, and oxidative stress, including that of VEGF-A, VEGFR-2, CD68, CTGF, and p22-phox. The stimulation of human adult retinal pigment epithelial (ARPE) cell line 19 cells with TGF-β2 and TNF-α induced epithelial-to-mesenchymal transition (EMT), whereas AM2 expression was also elevated. The induction of EMT was suppressed when the ARPE-19 cells were pretreated with AM2. A transcriptome analysis identified 15 genes, including mesenchyme homeobox 2 (Meox2), whose expression was significantly altered in the AM2-treated group compared with that in the control group. The expression of Meox2, a transcription factor that inhibits inflammation and fibrosis, was enhanced by AM2 treatment and attenuated by endogenous AM2 knockout in the early phase after laser irradiation. The AM2 treatment of endothelial cells inhibited endothelial to mesenchymal transition and NF-κB activation; however, this effect tended to be canceled following Meox2 gene knockdown. These results indicate that AM2 suppresses the neovascular age-related macular degeneration-related pathologies partially via the upregulation of Meox2. Thus, AM2 may be a promising therapeutic target for ocular vascular diseases.},
}
@article {pmid36869890,
year = {2023},
author = {Wada, I and Nakao, S and Fukuda, Y and Shiose, S and Takeda, A and Kannan, R and Sonoda, KH},
title = {Persistence of vascular empty sleeves in choroidal neovascularization after VEGF therapy in both animal models and humans.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {8},
pages = {2189-2197},
pmid = {36869890},
issn = {1435-702X},
support = {20K09829//JSPS KAKENHI/ ; EY30141/GF/NIH HHS/United States ; },
mesh = {Humans ; Mice ; Animals ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Collagen Type IV ; Retrospective Studies ; *Choroidal Neovascularization/drug therapy ; Vascular Endothelial Growth Factors ; Disease Models, Animal ; Intravitreal Injections ; Fluorescein Angiography ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: Choroidal neovascularization (CNV) often recurs during anti-vascular endothelial growth factor (VEGF) therapy; however, little is known about the mechanism of vascular regrowth. Vascular regrowth along the empty sleeves of basement membranes was proposed as a mechanism for recurrence after the reversal of VEGF inhibition in tumors. This study investigated whether the proposed mechanism is involved in CNV during VEGF therapy.<br><br>METHODS: We made two observations using a mice model, as well as patients with CNV. Laser-induced CNV mice were used to examine the vascular empty sleeves of the basement membrane and CNV with the immunohistochemistry of type IV collagen and CD31, respectively. A retrospective cohort study included 17 eyes from 17 patients with CNV treated with anti-VEGF treatment. Vascular regrowth during anti-VEGF treatment was assessed using optical coherence tomography angiography (OCTA).<br><br>RESULTS: In the CNV mouse model, the CD31[+] vascular endothelium area was decreased during anti-VEGF treatment compared with the IgG control (33516.7&#x2009;&#xb1;&#x2009;10864.7 vs. 10745.9&#x2009;&#xb1;&#x2009;5755.9 &#x3bc;m[2], P&#x2009;<&#x2009;0.05), whereas a significant difference was not observed in the area of type IV collagen[+] vascular empty sleeve after the treatment compared with the control (29135.0&#x2009;&#xb1;&#x2009;7432.9 vs. 24592.0&#x2009;&#xb1;&#x2009;5935.3 &#x3bc;m[2], P&#x2009;=&#x2009;0.7). The proportions of CD31[+] to type IV collagen[+] areas were significantly decreased after the treatment (38.7&#x2009;&#xb1;&#x2009;7.4% vs. 17.1&#x2009;&#xb1;&#x2009;5.4%, P&#x2009;<&#x2009;0.05). In the OCTA observations, the follow-up period in the retrospective cohort study was 58.2&#x2009;&#xb1;&#x2009;23.4&#xa0;months. CNV regrowth was observed in 682 neovessels of the 17 eyes. In group 1, CNV regression and regrowth are in the same form (129 neovessels, 18.9%). In group 2, CNV regression and regrowth are in a different form (170 neovessels, 24.9%). In group 3, CNV regrowth is with a different form without the regression (383 neovessels, 56.2%).<br><br>CONCLUSIONS: Parts of CNV regrowth may occur along the vascular empty sleeve, which remain after anti-VEGF treatment.},
}
@article {pmid36869310,
year = {2023},
author = {Shu, Y and Ye, F and Liu, H and Wei, J and Sun, X},
title = {Predictive value of pigment epithelial detachment markers for visual acuity outcomes in neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {83},
pmid = {36869310},
issn = {1471-2415},
support = {201409006700//Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan/ ; },
mesh = {Humans ; *Retinal Detachment ; *Retinal Diseases ; Retina ; *Orbital Diseases ; Polypoidal Choroidal Vasculopathy ; Visual Acuity ; *Macular Degeneration ; },
abstract = {BACKGROUND: To determine the predictive value of quantitative morphological parameters for pigment epithelial detachment (PED) of neovascular age-related macular degeneration (nAMD) patients.<br><br>METHODS: One eye from each of 159 patients with nAMD were studied. Polypoidal choroidal vasculopathy (PCV) group included 77 eyes, and non-PCV group 82. Patients received conbercept 0.05&#xa0;ml (0.5&#xa0;mg) in a 3&#x2009;+&#x2009;ProReNata (PRN) treatment regimen. Correlations between retinal morphologic parameters at baseline and best-corrected visual acuity (BCVA) gain at 3 or 12&#xa0;months after treatment (structure-function correlations) were assessed. Optical coherence tomography (OCT) scans were used to assess retinal morphologic features including intraretinal cystoid fluid (IRC), subretinal fluid (SRF), PED or PED type (PEDT), and vitreomacular adhesion (VMA). Greatest height (PEDH) and width of PED (PEDW), and volume of PED (PEDV) at baseline were also measured.<br><br>RESULTS: For non-PCV group, BCVA gain from 3 or 12&#xa0;months after treatment was&#xa0;negatively correlated with PEDV at baseline (r&#x2009;=&#x2009;-0.329, -0.312, P&#x2009;=&#x2009;0.027, 0.037). BCVA gain at 12&#xa0;months after treatment was negatively correlated with PEDW at baseline (r&#x2009;=&#x2009;-0.305, P&#x2009;=&#x2009;0.044). For PCV group, there were no correlations with PEDV, PEDH, PEDW, and PEDT in BCVA gain between baseline and 3 or 12&#xa0;months after treatment (P&#x2009;>&#x2009;0.05). SRF, IRC, VMA at baseline did not correlate with short-term and long-term BCVA gain in patients with nAMD (P&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: For patients with non-PCV, PEDV at baseline was negatively correlated with short-term and long-term BCVA gain, and PEDW was negatively correlated with long-term BCVA gain. On the contrary, quantitative morphological parameters for PED at baseline had no correlation with BCVA gain in patients with PCV.},
}
@article {pmid36869160,
year = {2023},
author = {He, J and Wang, J and Han, Z and Ma, J and Wang, C and Qi, M},
title = {An interpretable transformer network for the retinal disease classification using optical coherence tomography.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {3637},
pmid = {36869160},
issn = {2045-2322},
mesh = {Humans ; *Diabetic Retinopathy ; Tomography, Optical Coherence ; *Macular Edema ; *Retinal Diseases ; Retina ; },
abstract = {Retinal illnesses such as age-related macular degeneration and diabetic macular edema will lead to irreversible blindness. With optical coherence tomography (OCT), doctors are able to see cross-sections of the retinal layers and provide patients with a diagnosis. Manual reading of OCT images is time-consuming, labor-intensive and even error-prone. Computer-aided diagnosis algorithms improve efficiency by automatically analyzing and diagnosing retinal OCT images. However, the accuracy and interpretability of these algorithms can be further improved through effective feature extraction, loss optimization and visualization analysis. In this paper, we propose an interpretable Swin-Poly Transformer network for performing automatically retinal OCT image classification. By shifting the window partition, the Swin-Poly Transformer constructs connections between neighboring non-overlapping windows in the previous layer and thus has the flexibility to model multi-scale features. Besides, the Swin-Poly Transformer modifies the importance of polynomial bases to refine cross entropy for better retinal OCT image classification. In addition, the proposed method also provides confidence score maps, assisting medical practitioners to understand the models' decision-making process. Experiments in OCT2017 and OCT-C8 reveal that the proposed method outperforms both the convolutional neural network approach and ViT, with an accuracy of 99.80% and an AUC of 99.99%.},
}
@article {pmid36868191,
year = {2023},
author = {Dalvi, S and Chatterjee, A and Singh, R},
title = {AMD recapitulated in a 3D biomimetic: A breakthrough in retina tissue engineering.},
journal = {Cell stem cell},
volume = {30},
number = {3},
pages = {243-245},
doi = {10.1016/j.stem.2023.02.001},
pmid = {36868191},
issn = {1875-9777},
mesh = {Humans ; *Biomimetics ; Tissue Engineering ; Retina ; *Macular Degeneration ; },
abstract = {Song et al. (Nature Methods, 2022) engineered a 3D model of the human outer blood-retina barrier (oBRB) that recapitulates key features of healthy and age-related macular degeneration (AMD)-affected eyes.[1] We shine a spotlight on this tissue-engineering triumph that has the potential to transform preclinical studies of AMD and other eye diseases.},
}
@article {pmid36866844,
year = {2023},
author = {Mulpuri, L and Sridhar, J and Goyal, H and Tonk, R},
title = {The relationship between dietary patterns and ophthalmic disease.},
journal = {Current opinion in ophthalmology},
volume = {34},
number = {3},
pages = {189-194},
doi = {10.1097/ICU.0000000000000943},
pmid = {36866844},
issn = {1531-7021},
mesh = {Animals ; Humans ; *Diabetic Retinopathy/epidemiology/etiology/prevention &amp; control ; *Diet, Mediterranean ; *Macular Degeneration/epidemiology/etiology/prevention &amp; control ; *Cataract/epidemiology/etiology/prevention &amp; control ; Observational Studies as Topic ; },
abstract = {PURPOSE OF REVIEW: There is a rising interest in the impact of diet on the pathogenesis of common ophthalmic conditions. The purpose of this review is to summarize the potential preventive and therapeutic power of dietary interventions described in recent basic science and epidemiological literature.<br><br>RECENT FINDINGS: Basic science investigations have elucidated a variety of mechanisms by which diet may impact ophthalmic disease, particularly through its action on chronic oxidative stress, inflammation and macular pigmentation. Epidemiologic investigations have shown the real-world influence of diet on the incidence and progression of a number of ophthalmic diseases, particularly cataract, age-related macular degeneration (AMD) and diabetic retinopathy. A large observational cohort study found a 20% reduction in the incidence of cataract among vegetarians compared with nonvegetarians. Two recent systematic reviews found that higher adherence to Mediterranean dietary patterns was associated with a decreased risk of progression of AMD to later stages. Finally, large meta-analyses found that patients following plant-based and Mediterranean diets had significant reductions of mean haemoglobin A1c scores and incidence of diabetic retinopathy as compared with controls.<br><br>SUMMARY: There is a significant and growing body of evidence that Mediterranean diet and plant-based diets - those that maximize fruits, vegetables, legumes, whole grains and nuts; and that minimize animal products and processed foods - help prevent vision loss from cataract, AMD and diabetic retinopathy. These diets may hold benefits for other ophthalmic conditions, as well. Nevertheless, there is a need for further randomized, controlled and longitudinal studies in this area.},
}
@article {pmid36866159,
year = {2023},
author = {Zhang, Q and Wang, N and Rui, Y and Xia, Y and Xiong, S and Xia, X},
title = {New insight of metabolomics in ocular diseases in the context of 3P medicine.},
journal = {The EPMA journal},
volume = {14},
number = {1},
pages = {53-71},
pmid = {36866159},
issn = {1878-5077},
abstract = {Metabolomics refers to the high-through untargeted or targeted screening of metabolites in biofluids, cells, and tissues. Metabolome reflects the functional states of cells and organs of an individual, influenced by genes, RNA, proteins, and environment. Metabolomic analyses help to understand the interaction between metabolism and phenotype and reveal biomarkers for diseases. Advanced ocular diseases can lead to vision loss and blindness, reducing patients' quality of life and aggravating socio-economic burden. Contextually, the transition from reactive medicine to the predictive, preventive, and personalized (PPPM / 3P) medicine is needed. Clinicians and researchers dedicate a lot of efforts to explore effective ways for disease prevention, biomarkers for disease prediction, and personalized treatments, by taking advantages of metabolomics. In this way, metabolomics has great clinical utility in the primary and secondary care. In this review, we summarized much progress achieved by applying metabolomics to ocular diseases and pointed out potential biomarkers and metabolic pathways involved to promote 3P medicine approach in healthcare.},
}
@article {pmid36864830,
year = {2023},
author = {McGwin, G and Kar, D and Berlin, A and Clark, ME and Swain, TA and Crosson, JN and Sloan, KR and Owsley, C and Curcio, CA},
title = {Macular and Plasma Xanthophylls Are Higher in Age-related Macular Degeneration than in Normal Aging: Alabama Study on Early Age-related Macular Degeneration 2 Baseline.},
journal = {Ophthalmology science},
volume = {3},
number = {2},
pages = {100263},
pmid = {36864830},
issn = {2666-9145},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY027948/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Quantification of retinal xanthophyll carotenoids in eyes with and without age-related macular degeneration (AMD) via macular pigment optical volume (MPOV), a metric for xanthophyll abundance from dual wavelength autofluorescence, plus correlations to plasma levels, could clarify the role of lutein (L) and zeaxanthin (Z) in health, AMD progression, and supplementation strategies.<br><br>DESIGN: Cross-sectional observational study (NCT04112667).<br><br>PARTICIPANTS: Adults &#x2265; 60 years from a comprehensive ophthalmology clinic, with healthy maculas or maculas meeting fundus criteria for early or intermediate AMD.<br><br>METHODS: Macular health and supplement use was assessed by the Age-related Eye Disease Study (AREDS) 9-step scale and self-report, respectively. Macular pigment optical volume was measured from dual wavelength autofluorescence emissions (Spectralis, Heidelberg Engineering). Non-fasting blood draws were assayed for L and Z using high-performance liquid chromatography. Associations among plasma xanthophylls and MPOV were assessed adjusting for age.<br><br>MAIN OUTCOME MEASURES: Age-related macular degeneration presence and severity, MPOV in fovea-centered regions of radius 2.0&#xb0; and 9.0&#xb0;; plasma L and Z (&#x3bc;M/ml).<br><br>RESULTS: Of 809 eyes from 434 persons (89% aged 60-79, 61% female), 53.3% eyes were normal, 28.2% early AMD, and 18.5% intermediate AMD. Macular pigment optical volume 2&#xb0; and 9&#xb0; were similar in phakic and pseudophakic eyes, which were combined for analysis. Macular pigment optical volume 2&#xb0; and 9&#xb0; and plasma L and Z were higher in early AMD than normal and higher still in intermediate AMD (P&#xa0;<&#xa0;0.0001). For all participants, higher plasma L was correlated with higher MPOV 2&#xb0; (Spearman correlation coefficient [Rs]&#xa0;=&#xa0;0.49; P < 0.0001). These correlations were significant (P&#xa0;<&#xa0;0.0001) but lower in normal (Rs&#xa0;=&#xa0;0.37) than early and intermediate AMD (Rs&#xa0;=&#xa0;0.52 and 0.51, respectively). Results were similar for MPOV 9&#xb0;. Plasma Z, MPOV 2&#xb0;, and MPOV 9&#xb0; followed this same pattern of associations. Associations were not affected by supplement use or smoking status.<br><br>CONCLUSIONS: A moderate positive correlation of MPOV with plasma L and Z comports with regulated xanthophyll bioavailability and a hypothesized role for xanthophyll transfer in soft drusen biology. An assumption that xanthophylls are low in AMD retina underlies supplementation strategies to reduce progression risk, which our data do not support. Whether higher xanthophyll levels in AMD are due to supplement use cannot be determined in this study.},
}
@article {pmid36864662,
year = {2024},
author = {Millen, AE and Dighe, S and Kordas, K and Aminigo, BZ and Zafron, ML and Mu, L},
title = {Air Pollution and Chronic Eye Disease in Adults: A Scoping Review.},
journal = {Ophthalmic epidemiology},
volume = {31},
number = {1},
pages = {1-10},
doi = {10.1080/09286586.2023.2183513},
pmid = {36864662},
issn = {1744-5086},
mesh = {Adult ; Humans ; Air Pollutants/adverse effects/analysis ; *Air Pollution/adverse effects/analysis ; Cataract/epidemiology/etiology ; Cross-Sectional Studies ; Environmental Exposure/adverse effects/analysis ; *Eye Diseases/etiology/chemically induced ; },
abstract = {PURPOSE: We conducted a scoping review of studies examining ambient air pollution as a risk factor for chronic eye disease influencing the lens, retina, and intraocular pressure in adults.<br><br>METHODS: Terms related to air pollution and eye disease outcomes were used to search for publications on Embase, Web of Science Core Collection, Global Health, PubMed, and the Cochrane Central Register of Controlled Trials from January 1, 2010, through April 11, 2022.<br><br>RESULTS: We identified 27 articles, focusing on the following non-mutually exclusive outcomes: cataract (n&#xa0;=&#xa0;9), presbyopia (n&#xa0;=&#xa0;1), retinal vein occlusion or central retinal arteriolar and venular equivalents (n&#xa0;=&#xa0;5), intraocular pressure (IOP) (n&#xa0;=&#xa0;3), glaucoma (n&#xa0;=&#xa0;5), age-related macular degeneration (AMD) (n&#xa0;=&#xa0;5), diabetic retinopathy (n&#xa0;=&#xa0;2), and measures of retinal morphology (n&#xa0;=&#xa0;3). Study designs included cross-sectional (n&#xa0;=&#xa0;16), case-control (n&#xa0;=&#xa0;4), and longitudinal (n&#xa0;=&#xa0;7). Air pollutants were measured in 50% and 95% of the studies on lens and retina or IOP, respectively, and these exposures were assigned to geographic locations. Most research was conducted in global regions with high exposure to air pollution. Consistent associations suggested a possibly increased risk of cataract and retina-associated chronic eye disease with increasing exposure to particulate matter (PM2.5-PM10), NO2, NOx, and SO2. Associations with O3 were less consistent.<br><br>CONCLUSIONS: Accumulating research suggests air pollution may be a modifiable risk factor for chronic eye diseases of the lens and retina. The number of studies on each specific lens- or retina-related outcome is limited. Guidelines regarding the role of air pollution in chronic eye disease do not exist.},
}
@article {pmid36862121,
year = {2023},
author = {Edwards, MM and McLeod, DS and Shen, M and Grebe, R and Sunness, JS and Bhutto, IA and McDonnell, E and Pado, AM and Gregori, G and Rosenfeld, PJ and Lutty, GA},
title = {Clinicopathologic Findings in Three Siblings With Geographic Atrophy.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {3},
pages = {2},
pmid = {36862121},
issn = {1552-5783},
support = {P30 EY001765/EY/NEI NIH HHS/United States ; R01 EY016151/EY/NEI NIH HHS/United States ; R01 EY031044/EY/NEI NIH HHS/United States ; },
mesh = {Male ; Aged ; Humans ; *Geographic Atrophy/diagnosis ; Siblings ; *Macular Degeneration ; Retina/diagnostic imaging ; Retinal Pigment Epithelium ; *Choroidal Neovascularization ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Clinical imaging and histopathologic studies are crucial to understanding disease pathology. This study combined clinical observations of three brothers with geographic atrophy (GA), followed for 20 years, with histopathologic analysis.<br><br>METHODS: For two of the three brothers, clinical images were taken in 2016, 2 years prior to death. Immunohistochemistry, on both flat-mounts and cross sections, histology, and transmission electron microscopy were used to compare the choroid and retina in GA eyes to those of age-matched controls.<br><br>RESULTS: Ulex europaeus agglutinin (UEA) lectin staining of the choroid demonstrated a significant reduction in the percent vascular area and vessel diameter. In one donor, histopathologic analysis demonstrated two separate areas with choroidal neovascularization (CNV). Reevaluation of swept-source optical coherence tomography angiography (SS-OCTA) images revealed CNV in two of the brothers. UEA lectin also revealed a significant reduction in retinal vasculature in the atrophic area. A subretinal glial membrane, composed of processes positive for glial fibrillary acidic protein and/or vimentin, occupied areas identical to those of retinal pigment epithelium (RPE) and choroidal atrophy in all three AMD donors. SS-OCTA also demonstrated presumed calcific drusen in the two donors imaged in 2016. Immunohistochemical analysis and alizarin red S staining verified calcium within drusen, which was ensheathed by glial processes.<br><br>CONCLUSIONS: This study demonstrates the importance of clinicohistopathologic correlation studies. It emphasizes the need to better understand how the symbiotic relationship between choriocapillaris and RPE, glial response, and calcified drusen impact GA progression.},
}
@article {pmid36859600,
year = {2023},
author = {Nichani, PAH and Popovic, MM and Dhoot, AS and Pathak, A and Muni, RH and Kertes, PJ},
title = {Treat-and-extend dosing of intravitreal anti-VEGF agents in neovascular age-related macular degeneration: a meta-analysis.},
journal = {Eye (London, England)},
volume = {37},
number = {14},
pages = {2855-2863},
pmid = {36859600},
issn = {1476-5454},
mesh = {Humans ; Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Treatment Outcome ; Visual Acuity ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {Intravitreal injections of antiangiogenic agents are pivotal in treating neovascular age-related macular degeneration (nAMD). The comparative efficacy and safety of treat-and-extend (T&amp;E) versus bimonthly, monthly, and pro re nata (PRN) dosing remains unclear. A systematic review and meta-analysis of English-language RCTs reporting on efficacy and/or safety outcomes of dosing regimens of anti-VEGF agents in nAMD was performed. Best-corrected visual acuity (BCVA, ETDRS letters) at last follow-up represented the primary endpoint, while central subfield thickness (CSFT, μm), injection burden, and ocular adverse events were secondary endpoints. A random effects meta-analysis was performed, and 95% confidence intervals were calculated. Across six RCTs, 781 T&amp;E-, 663 monthly-, 130 PRN-, and 123 bimonthly treated eyes were included. Mean changes in BCVA and CSFT at last follow-up were similar between T&amp;E versus monthly (WMD, -0.62 letters; 95% CI, -2.12 to 0.87; P = 0.41; WMD, 5.30 microns; 95% CI, -10.67 to 21.26; P = 0.52, respectively), bimonthly (WMD, 1.68 letters; 95% CI, -3.55 to 6.91; P = 0.53; WMD, -18.91 microns; 95% CI, -46.41 to 8.60; P = 0.18, respectively), and PRN (BCVA WMD, 1.08 letters; 95% CI, -2.95 to 5.11; P = 0.60) regimens. T&amp;E was associated with a reduced injection burden versus monthly (WMD, -4.52 injections; 95% CI, -6.66 to 2.39; P < 0.001) but higher injection burden versus PRN (WMD, 1.81 injections; 95% CI, 1.12 to 2.51; P < 0.001) dosing. There was no significant difference in safety outcomes amongst comparators. There was no significant difference in efficacy and safety between T&amp;E, bimonthly, monthly, and PRN dosing. T&amp;E resulted in fewer injections versus monthly and fewer clinic visits versus PRN.},
}
@article {pmid36859261,
year = {2023},
author = {Su, W and Liu, C and Jiang, X and Lv, Y and Chen, Q and Shi, J and Zhang, H and Ma, Q and Ge, C and Kong, F and Li, X and Liu, Y and Chen, Y and Qu, D},
title = {An intravitreal-injectable hydrogel depot doped borneol-decorated dual-drug-coloaded microemulsions for long-lasting retina delivery and synergistic therapy of wAMD.},
journal = {Journal of nanobiotechnology},
volume = {21},
number = {1},
pages = {71},
pmid = {36859261},
issn = {1477-3155},
support = {M2021010//General Project of Jiangsu Provincial Health Commission/ ; 82173980//National Natural Science Foundation of China/ ; 2020YLXK015//the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine/ ; YY-028-2019//the Six Talent Peak Project of Jiangsu Province/ ; BK20211389//Natural Science Foundation of Jiangsu Province of China/ ; },
mesh = {Animals ; Mice ; *Hydrogels ; *Retina ; Anthraquinones ; },
abstract = {Sustained retina drug delivery and rational drug combination are considered essential for enhancing the efficacy of therapy for wet age-related macular degeneration (wAMD) due to the conservative structure of the posterior ocular segment and the multi-factorial pathological mechanism. Designing a drug co-delivery system that can simultaneously achieve deep penetration and long-lasting retention in the vitreous is highly desired, yet remains a huge challenge. In this study, we fabricated Bor/RB-M@TRG as an intravitreal-injectable hydrogel depot for deep penetration into the posterior ocular segment and long-lasting distribution in the retinal pigment epithelium (RPE) layer. The Bor/RB-M@TRG consisted of borneol-decorated rhein and baicalein-coloaded microemulsions (Bor/RB-M, the therapy entity) and a temperature-responsive hydrogel matrix (the intravitreal depot). Bor/RB-M exhibited the strongest in vitro anti-angiogenic effects among all the groups studied, which is potentially associated with improved cellular uptake, as well as the synergism of rhein and baicalein, acting via anti-angiogenic and anti-oxidative stress pathways, respectively. Importantly, a single intravitreal (IVT) injection with Bor/RB-M@TRG displayed significant inhibition against the CNV of wAMD model mice, compared to all other groups. Particularly, coumarin-6-labeled Bor/RB-M@TRG (Bor/C6-M@TRG) could not only deeply penetrate into the retina but also stably accumulate in the RPE layer for at least 14 days. Our design integrates the advantages of borneol-decorated microemulsions and hydrogel depots, offering a promising new approach for clinically-translatable retinal drug delivery and synergistic anti-wAMD treatment.},
}
@article {pmid36858288,
year = {2023},
author = {Khurana, RN and Li, C and Lum, F},
title = {Loss to Follow-up in Patients with Neovascular Age-Related Macular Degeneration Treated with Anti-VEGF Therapy in the United States in the IRIS® Registry.},
journal = {Ophthalmology},
volume = {130},
number = {7},
pages = {672-683},
doi = {10.1016/j.ophtha.2023.02.021},
pmid = {36858288},
issn = {1549-4713},
mesh = {Humans ; Male ; Aged ; United States/epidemiology ; Aged, 80 and over ; *Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Medicare ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Intravitreal Injections ; },
abstract = {PURPOSE: To determine the incidence of being lost to follow-up (LTFU) and nonpersistence in patients with neovascular age-related macular degeneration (AMD) treated with anti-VEGF injections in the United States.<br><br>DESIGN: Retrospective cohort study using the IRIS&#xae; (Intelligent Research in Sight) Registry data.<br><br>PARTICIPANTS: One hundred fifty-six thousand three hundred twenty-seven treatment-naive patients with neovascular AMD who subsequently were treated with anti-VEGF therapy from 2013 through 2015 and followed up through&#xa0;2019.<br><br>METHODS: Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).<br><br>MAIN OUTCOME MEASURES: Being LTFU was defined as no follow-up within 12 months from last intravitreal injection. Nonpersistence was defined as no follow-up within 6 months from last intravitreal injection.<br><br>RESULTS: For neovascular AMD, 11.6% of patients (95% CI, 11.4%-11.7%) were LTFU, and 88.4% of patients were followed up within 12 months. The rate of being LTFU generally was higher with increasing age, with odds of being LTFU greatest for patients between 81 and 84 years of age (OR, 2.51; 95% CI, 2.31-2.74; P < 0.001) compared with patients 70 years of age and younger. Odds of being LTFU for Black or African American patients (OR, 1.32; 95% CI, 1.08-1.61; P&#xa0;= 0.007) were greater than for White patients. Odds of being LTFU were higher for patients with Medicaid insurance (OR, 1.27; 95% CI, 1.01-1.60; P&#xa0;= 0.04) and lower for patients with Medicare Fee-For-Service insurance (OR, 0.69; 95% CI, 0.64-0.74; P < 0.001) than for patients with private insurance. Furthermore, 14.3% (95% CI, 14.1-14.4) of patients were nonpersistent, and 85.7% of patients underwent follow-up within 6 months. Odds of nonpersistence also were greatest among patients between 81 and 84 years of age (OR, 2.13; 95% CI, 1.98-2.29; P < 0.001) compared with patients 70 years of age or younger. Odds of nonpersistence for Black or African-American patients (OR, 1.38; 95% CI, 1.15-1.65; P < 0.001) and Hispanic patients (OR, 1.13; 95% CI, 1.03-1.24; P&#xa0;= 0.009) were greater than odds for White patients.<br><br>CONCLUSIONS: Nearly 1 of 9 patients with neovascular AMD treated with anti-VEGF injections became LTFU, whereas 1 of 7 patients were nonpersistent. Risk factors identified included increasing age, male sex, unilateral involvement, diabetes, Medicaid insurance, and race or ethnicity.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36857076,
year = {2023},
author = {Guadron, L and Titchener, SA and Abbott, CJ and Ayton, LN and van Opstal, J and Petoe, MA and Goossens, J},
title = {The Saccade Main Sequence in Patients With Retinitis Pigmentosa and Advanced Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {3},
pages = {1},
pmid = {36857076},
issn = {1552-5783},
support = {693400/ERC_/European Research Council/International ; },
mesh = {Humans ; Saccades ; *Retinitis Pigmentosa ; Eye Movements ; *Retinal Diseases ; *Macular Degeneration ; Scotoma ; },
abstract = {PURPOSE: Most eye-movement studies in patients with visual field defects have examined the strategies that patients use while exploring a visual scene, but they have not investigated saccade kinematics. In healthy vision, saccade trajectories follow the remarkably stereotyped "main sequence": saccade duration increases linearly with saccade amplitude; peak velocity also increases linearly for small amplitudes, but approaches a saturation limit for large amplitudes. Recent theories propose that these relationships reflect the brain's attempt to optimize vision when planning eye movements. Therefore, in patients with bilateral retinal damage, saccadic behavior might differ to optimize vision under the constraints imposed by the visual field defects.<br><br>METHODS: We compared saccadic behavior of patients with central vision loss, due to age-related macular degeneration (AMD), and patients with peripheral vision loss, due to retinitis pigmentosa (RP), to that of controls with normal vision (NV) using a horizontal saccade task.<br><br>RESULTS: Both patient groups demonstrated deficits in saccade reaction times and target localization behavior, as well as altered saccade kinematics. Saccades were generally slower and the shape of the velocity profiles were often atypical, especially in the patients with RP. In the patients with AMD, the changes were far less dramatic. For both groups, saccade kinematics were affected most when the target was in the subjects' blind field.<br><br>CONCLUSIONS: We conclude that defects of the central and peripheral retina have distinct effects on the saccade main sequence, and that visual inputs play an important role in planning the kinematics of a saccade.},
}
@article {pmid36855186,
year = {2023},
author = {Zhao, X and Zhao, Q and Wang, E and Li, N and Meng, L and Zhang, W and Wang, T and Chen, Y and Min, H},
title = {Three-dimensional heads-up system assisted pars plana vitrectomy and subretinal recombinant tissue plasminogen activator injection for submacular hemorrhage.},
journal = {Eye and vision (London, England)},
volume = {10},
number = {1},
pages = {8},
pmid = {36855186},
issn = {2326-0254},
abstract = {BACKGROUND: To evaluate the outcomes of three-dimensional (3D) heads-up system assisted pars plana vitrectomy (PPV) and subretinal injection of recombinant tissue plasminogen activator (rt-PA) for submacular hemorrhage (SMH).<br><br>METHODS: Medical records of SMH patients who underwent 3D heads-up system assisted-PPV and subretinal injection of rt-PA from June 2021 to January 2022 were reviewed. The main outcomes included best-corrected visual acuity (BCVA), SMH absorption, and perioperative complications.<br><br>RESULTS: We finally included 18 SMH eyes, most of which happened secondary to polypoidal choroidal vasculopathy (PCV) (10, 55.56%), followed by retinal arterial microaneurysm (RAM) (5, 27.78%), traumatic retinopathy (2, 11.11%) and neovascular age-related macular degeneration (nAMD) (1, 5.56%). The greatest linear dimension (GLD) and height of SMH were 6538.17&#x2009;&#xb1;&#x2009;2533.11&#xa0;&#x3bc;m and 937.36&#x2009;&#xb1;&#x2009;420.21&#xa0;&#x3bc;m, respectively. After an average postoperative follow-up period of 131.06&#x2009;&#xb1;&#x2009;38.96&#xa0;days, patients' BCVA improved significantly from 1.85&#x2009;&#xb1;&#x2009;0.62 to 1.14&#x2009;&#xb1;&#x2009;0.82 logMAR (P&#x2009;<&#x2009;0.05). SMH was completely and partially absorbed in 9 (50.00%) and 6 (33.33%) eyes, with no occurrence of iatrogenic retinal break. However, 4 additional PPVs were performed to manage the postoperative SMH and/or vitreous hemorrhage (VH) recurrence (2, 11.11%) and retinal detachment (RD) occurrence (2, 11.11%). Preoperative BCVA was significantly correlated with postoperative BCVA in multiple linear regression analysis (P&#x2009;<&#x2009;0.05), and hemorrhagic pigment epithelial detachment (PED) was significantly correlated with SMH and VH recurrence in univariate binary logistic regression analysis (P&#x2009;<&#x2009;0.05).<br><br>CONCLUSIONS: The 3D heads-up system assisted-PPV and subretinal injection of rt-PA were efficacious in eliminating SMH and improving visual prognosis with satisfactory safety profile, while caution should be taken for PCV patients with hemorrhagic PED and massive SMH.},
}
@article {pmid36854371,
year = {2023},
author = {Rispoli, M and Cennamo, G and Antonio, LD and Lupidi, M and Parravano, M and Pellegrini, M and Veritti, D and Vujosevic, S and Savastano, MC},
title = {Practical guidance for imaging biomarkers in exudative age-related macular degeneration.},
journal = {Survey of ophthalmology},
volume = {68},
number = {4},
pages = {615-627},
doi = {10.1016/j.survophthal.2023.02.004},
pmid = {36854371},
issn = {1879-3304},
mesh = {Humans ; *Choroidal Neovascularization ; Angiogenesis Inhibitors ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/diagnosis ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; },
abstract = {We provide an overview of current macular imaging techniques and identify and describe biomarkers that may be of use in the routine management of macular diseases, particularly exudative age-related macular degeneration (AMD). This perspective includes sections on macular imaging techniques including optical coherence tomography (OCT) and OCT angiography (OCTA), classification of exudative AMD, and biomarkers in structural OCT and OCTA. Fluorescein angiography remains a vital tool for assessing the activity of neovascular lesions, while indocyanine green angiography is the preferred option for choroidal vessel imaging in neovascular AMD. OCT provides a non-invasive three-dimensional visualization of retinal architecture in vivo and is useful in the diagnosis of many imaging biomarkers of AMD-related neovascular lesions, including lesion activity. OCTA is a recent advance in OCT technology that allows accurate visualization of retinal and choroidal vascular flow. OCT and OCTA have led to an updated classification of exudative AMD lesions and provide several biomarkers that help to establish a diagnosis and the disease activity status of neovascular lesions. Individualization of therapy guided by OCT and OCTA biomarkers has the potential to further improve visual outcomes in exudative AMD. Moving forwards, integration of technologically-advanced imaging equipment with AI software will help ophthalmologists to provide patients with the best possible care.},
}
@article {pmid36849907,
year = {2023},
author = {Zhao, B and Zhu, L and Ye, M and Lou, X and Mou, Q and Hu, Y and Zhang, H and Zhao, Y},
title = {Oxidative stress and epigenetics in ocular vascular aging: an updated review.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {29},
number = {1},
pages = {28},
pmid = {36849907},
issn = {1528-3658},
mesh = {Humans ; *Oxidative Stress/genetics ; Epigenesis, Genetic ; Epigenomics ; *Macular Degeneration/genetics ; },
abstract = {Vascular aging is an inevitable process with advancing age, which plays a crucial role in the pathogenesis of cardiovascular and microvascular diseases. Diabetic retinopathy (DR) and age-related macular degeneration (AMD), characterized by microvascular dysfunction, are the common causes of irreversible blindness worldwide, however there is still a lack of effective therapeutic strategies for rescuing the visual function. In order to develop novel treatments, it is essential to illuminate the pathological mechanisms underlying the vascular aging during DR and AMD progression. In this review, we have summarized the recent discoveries of the effects of oxidative stress and epigenetics on microvascular degeneration, which could provide potential therapeutic targets for DR and AMD.},
}
@article {pmid36849659,
year = {2023},
author = {Shi, X and Xue, Z and Ye, K and Yuan, J and Zhang, Y and Qu, J and Su, J},
title = {Roles of non-coding RNAs in eye development and diseases.},
journal = {Wiley interdisciplinary reviews. RNA},
volume = {14},
number = {5},
pages = {e1785},
doi = {10.1002/wrna.1785},
pmid = {36849659},
issn = {1757-7012},
mesh = {RNA ; RNA, Untranslated/genetics ; Humans ; RNA Interference ; Retinal Diseases/congenital ; *Eye Diseases/genetics ; },
abstract = {The prevalence of ocular disorders is dramatically increasing worldwide, especially those that cause visual impairment and permanent loss of vision, including cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy. Extensive evidence has shown that ncRNAs are key regulators in various biogenesis and biological functions, controlling gene expression related to histogenesis and cell differentiation in ocular tissues. Aberrant expression and function of ncRNA can lead to dysfunction of visual system and mediate progression of eye disorders. Here, we mainly offer an overview of the role of precise modulation of ncRNAs in eye development and function in patients with eye diseases. We also highlight the challenges and future perspectives in conducting ncRNA studies, focusing specifically on the role of ncRNAs that may hold expanded promise for their diagnostic and therapeutic applications in various eye diseases. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA in Disease and Development > RNA in Disease RNA in Disease and Development > RNA in Development.},
}
@article {pmid36849037,
year = {2023},
author = {Obasanmi, G and Zeglinski, MR and Hardie, E and Wilhelm, AC and Turner, CT and Hiroyasu, S and Boivin, WA and Tian, Y and Zhao, H and To, E and Cui, JZ and Xi, J and Yoo, HS and Uppal, M and Granville, DJ and Matsubara, JA},
title = {Granzyme B Contributes to Choroidal Neovascularization and Age-Related Macular Degeneration Through Proteolysis of Thrombospondin-1.},
journal = {Laboratory investigation; a journal of technical methods and pathology},
volume = {103},
number = {6},
pages = {100123},
doi = {10.1016/j.labinv.2023.100123},
pmid = {36849037},
issn = {1530-0307},
mesh = {Humans ; Aged ; Thrombospondin 1/metabolism ; Granzymes/metabolism ; Proteolysis ; *Macular Degeneration/complications/metabolism/pathology ; *Choroidal Neovascularization/drug therapy/etiology/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly. The pathology of neovascular age-related macular degeneration (nAMD), also known as wet AMD, is associated with an abnormal blood vessel growth in the eye and involves an imbalance of proangiogenic and antiangiogenic factors. Thrombospondin (TSP)-1 and TSP-2 are endogenous matricellular proteins that inhibit angiogenesis. TSP-1 is significantly diminished in eyes with AMD, although the mechanisms involved in its reduction are unknown. Granzyme B (GzmB) is a serine protease with an increased extracellular activity in the outer retina and choroid of human eyes with nAMD-related choroidal neovascularization (CNV). This study investigated whether TSP-1 and TSP-2 are GzmB substrates using in silico and cell-free cleavage assays and explored the relationship between GzmB and TSP-1 in human eyes with nAMD-related CNV and the effect of GzmB on TSP-1 in retinal pigment epithelial culture and an explant choroid sprouting assay (CSA). In this study, TSP-1 and TSP-2 were identified as GzmB substrates. Cell-free cleavage assays substantiated the GzmB proteolysis of TSP-1 and TSP-2 by showing dose-dependent and time-dependent cleavage products. TSP-1 and TSP-2 proteolysis were hindered by the inhibition of GzmB. In the retinal pigment epithelium and choroid of human eyes with CNV, we observed a significant inverse correlation between TSP-1 and GzmB, as indicated by lower TSP-1 and higher GzmB immunoreactivity. In CSA, the vascular sprouting area increased significantly with GzmB treatment and reduced significantly with TSP-1 treatment. Western blot showed significantly reduced expression of TSP-1 in GzmB-treated retinal pigment epithelial cell culture and CSA supernatant compared with that in controls. Together, our findings suggest that the proteolysis of antiangiogenic factors such as TSP-1 by extracellular GzmB might represent a mechanism through which GzmB may contribute to nAMD-related CNV. Future studies are needed to investigate whether pharmacologic inhibition of extracellular GzmB can mitigate nAMD-related CNV by preserving intact TSP-1.},
}
@article {pmid36848049,
year = {2023},
author = {Zhang, X and Wang, S and Du, Z and Seth, I and Wang, Y and Liang, Y and Wu, G and Huang, Y and Liu, S and Hu, Y and Shang, X and Hu, Y and Zhu, Z and Yu, H},
title = {The associations and mediators between visual disabilities and anxiety disorders in middle-aged and older adults: A population-based study.},
journal = {The American psychologist},
volume = {78},
number = {8},
pages = {982-994},
doi = {10.1037/amp0001143},
pmid = {36848049},
issn = {1935-990X},
support = {//National Natural Science Foundation of China/ ; //Science and Technology Program of Guangzhou/ ; //Guangdong Provincial People's Hospital; Outstanding Young Talent Trainee Program/ ; //China Postdoctoral Science Foundation/ ; //Guangdong People's Hospital Research Funds for Postdoctoral Startups/ ; },
mesh = {Middle Aged ; Humans ; Aged ; Prospective Studies ; *Cataract ; Anxiety Disorders/complications/epidemiology ; Visual Acuity ; Anxiety/psychology ; },
abstract = {Visual disabilities significantly impact an individual's mental health. Little is known about the prospective relationship between visual disabilities and anxiety disorders and the underlying effects of modifiable risk factors. Our analysis was based on 117,252 participants from the U.K. Biobank, with baseline data collected between 2006 and 2010. Habitual visual acuity was measured by a standardized logarithmic chart, and ocular disorders reported using questionnaires were collected at baseline. Incident hospitalized anxiety recorded using longitudinal linkage with hospital inpatient data, lifetime anxiety disorder, and current anxiety symptoms assessed by a comprehensive online mental health questionnaire were identified over a 10-year follow-up. After adjustments for confounding factors, one-line worse visual acuity (0.1 logarithm of the minimum angle of resolution [logMAR]) was associated with an increased risk of incident hospitalized anxiety (HR = 1.05, 95% CI = 1.01-1.08), lifetime anxiety disorder (OR = 1.07, 95% CI [1.01-1.12]), and current anxiety scores (β = 0.028, 95% CI [0.002-0.054]). Besides poorer visual acuity, the longitudinal analysis also supported that each ocular disorder (including cataracts, glaucoma, macular degeneration, and diabetes-related eye disease) was significantly associated with at least two anxiety outcomes. Mediation analyses highlighted that subsequent onsets of eye diseases, especially cataracts, and lower socioeconomic status (SES) partly mediated the association between poorer visual acuity and anxiety disorders. This study demonstrates an overall association between visual disabilities and anxiety disorders in middle-aged and older adults. In particular, early interventions involving treatments for visual disabilities and effective psychological counseling services sensitive to socioeconomic status may help prevent anxiety in those living with poor vision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).},
}
@article {pmid36847632,
year = {2023},
author = {Ersöz, MG and Hocaoğlu, M and Sayman Muslubaş, I and Arf, S and Yıldız, E and Karaçorlu, M},
title = {Artifact-Removed Quantitative Analysis of Choriocapillaris Flow Voids.},
journal = {Turkish journal of ophthalmology},
volume = {53},
number = {1},
pages = {37-43},
pmid = {36847632},
issn = {2149-8709},
mesh = {Humans ; *Artifacts ; Retrospective Studies ; Choroid ; Retina ; *Retinal Detachment/diagnosis ; },
abstract = {OBJECTIVES: To investigate choriocapillaris flow voids (FV) with a new optical coherence tomography angiography (OCTA) image processing strategy that can eliminate artifacts caused by vitreous opacities, sub-retinal pigment epithelium fluid and deposits, and subretinal fluid (SRF) by thresholding the en-face OCT image of the outer retina.<br><br>MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with drusen and patients with active central serous chorioretinopathy (CSC). FV number (FVn), average area (FVav), and maximum area (FVmax) and the percentage of nonperfused choriocapillaris area (PNPCA) obtained using the proposed strategy were compared with those obtained by removing only artifacts caused by the superficial capillary plexus (SCP).<br><br>RESULTS: The SRF group included 21 eyes with active CSC and the drusen group included 29 eyes with nonexudative age-related macular degeneration. FVav, FVmax, FVn, and PNPCA obtained using the algorithm were significantly lower than those obtained by removing only SCP-related artefacts in both groups (all p<0.05). The algorithm was also able to remove 96.9% of artifacts secondary to vitreous opacities and all artifacts secondary to serous pigment epithelial detachments.<br><br>CONCLUSION: Choriocapillaris nonperfusion areas on OCTA images may be overestimated in eyes with RPE abnormalities and SRF due to artifacts. These artifact areas on choriocapillaris OCTA images can be removed using thresholded images of the outer retina en-face OCT scans. Our new artifact-removal strategy is useful in the assessment of choriocapillaris FV in eyes with SRF, drusen, drusen-like deposits, and pigment epithelial detachment.},
}
@article {pmid36847399,
year = {2023},
author = {Zeng, H and Yang, Q and Chen, J and Ding, L and Rao, F and Lv, J and Xie, B and Xiang, S and Yu, H and Chen, X and Wu, K and Chen, Q and Xiang, L},
title = {Image-Guided Optical Coherence Tomography to Assess Structural Changes in Rodent Retinas.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {192},
pages = {},
doi = {10.3791/64783},
pmid = {36847399},
issn = {1940-087X},
mesh = {Animals ; Tomography, Optical Coherence/methods ; Rodentia ; Retina/diagnostic imaging/pathology ; *Macular Degeneration/pathology ; *Glaucoma/pathology ; },
abstract = {Ocular diseases, such as age-related macular degeneration, glaucoma, retinitis pigmentosa, and uveitis, are always accompanied by retinal structural changes. These diseases affecting the fundus always exhibit typical abnormalities in certain cell types in the retina, including photoreceptor cells, retinal ganglion cells, cells in the retinal blood vessels, and cells in the choroidal vascular cells. Noninvasive, highly efficient, and adaptable imaging techniques are required for both clinical practice and basic research. Image-guided optical coherence tomography (OCT) satisfies these requirements because it combines fundus photography and high-resolution OCT, providing an accurate diagnosis of tiny lesions as well as important changes in the retinal architecture. This study details the procedures of data collection and data analysis for image-guided OCT and demonstrates its application in rodent models of choroidal neovascularization (CNV), optic nerve crush (ONC), light-induced retinal degeneration, and experimental autoimmune uveitis (EAU). This technique helps researchers in the eye field to identify rodent retinal structural changes conveniently, reliably, and tractably.},
}
@article {pmid36846451,
year = {2023},
author = {Zult, T and Timmis, MA and Pardhan, S},
title = {The effects of age and central field loss on maintaining balance control when stepping up to a new level under time-pressure.},
journal = {PeerJ},
volume = {11},
number = {},
pages = {e14743},
pmid = {36846451},
issn = {2167-8359},
mesh = {Young Adult ; Humans ; *Postural Balance ; *Walking ; },
abstract = {OBJECTIVE: To investigate the effects of age and central field loss on the landing mechanics and balance control when stepping up to a new level under time-pressure.<br><br>METHODS: Eight older individuals with age-related macular degeneration (AMD), eight visually normal older and eight visually normal younger individuals negotiated a floor-based obstacle followed by a 'step-up to a new level' task. The task was performed under (1) no-pressure; (2) time-pressure: an intermittent tone was played that increased in frequency and participants had to complete the task before the tone ceased. Landing mechanics and balance control for the step-up task was assessed with a floor-mounted force plate on the step.<br><br>RESULTS: Increased ground reaction forces and loading rates were observed under time-pressure for young and older visual normals but not for AMD participants. Across conditions, loading rates and ground reaction forces were higher in young normals compared to older normals and AMD participants. Young visual normals also demonstrated 35-39% shorter double support times prior to and during the step-up compared to older normals and AMD participants. All groups shortened their double support times (31-40%) and single support times (7-9%) in the time-pressure compared to no-pressure condition. Regarding balance control, the centre-of-pressure displacement and velocity in the anterior-poster direction were increased under time-pressure for young and older visual normals but not for AMD participants. The centre-of-pressure displacement and velocity in the medial-lateral direction were decreased for the AMD participants under time-pressure but not for young and older visual normals.<br><br>CONCLUSIONS: Despite walking faster, AMD participants did not adapt their landing mechanics under time-pressure (i.e., they remained more cautious), whilst older and young adults with normal vision demonstrated more forceful landing mechanics with the young being most forceful. A more controlled landing might be a safety strategy to maintain balance control during the step-up, especially in time-pressure conditions when balance control in the anterior-posterior direction is more challenged.},
}
@article {pmid36845999,
year = {2023},
author = {Zhao, H and Wang, M and Peng, X and Zhong, L and Liu, X and Shi, Y and Li, Y and Chen, Y and Tang, S},
title = {Fish consumption in multiple health outcomes: an umbrella review of meta-analyses of observational and clinical studies.},
journal = {Annals of translational medicine},
volume = {11},
number = {3},
pages = {152},
pmid = {36845999},
issn = {2305-5839},
abstract = {BACKGROUND: Omega-3 polyunsaturated fatty acids are known to be associated with numbers of health benefits, and which can be uptake from fish. The aim of this study was to evaluate the current evidence of associations between consumption of fish and diverse health outcomes. Here, we performed an umbrella review to summarize the breadth, strength, and validity of the evidence derived from meta-analyses and systematic reviews of fish consumption on all health outcomes.<br><br>METHODS: The methodological quality of the included meta-analyses and the quality of the evidence were assessed by the Assessment of Multiple Systematic Reviews (AMSTAR) and the grading of recommendations, assessment, development, and evaluation (GRADE) tools, respectively. The umbrella review identified 91 meta-analyses with 66 unique health outcomes, of which 32 outcomes were beneficial, 34 showed nonsignificant associations and only one was harmful (myeloid leukemia).<br><br>RESULTS: A total of 17 beneficial associations [all-cause mortality, prostate cancer mortality, cardiovascular disease (CVD) mortality, esophageal squamous cell carcinoma (ESCC), glioma, non-Hodgkin lymphoma (NHL), oral cancer, acute coronary syndrome (ACS), cerebrovascular disease, metabolic syndrome, age-related macular degeneration (AMD), inflammatory bowel disease (IBD), Crohn's disease (CD), triglycerides, vitamin D, high-density lipoprotein (HDL)-cholesterol, and multiple sclerosis (MS)], and eight nonsignificant associations [colorectal cancer (CRC) mortality, esophageal adenocarcinoma (EAC), prostate cancer, renal cancer, ovarian cancer, hypertension, ulcerative colitis (UC), and rheumatoid arthritis (RA)] were evaluated as moderate/high quality of evidence. According to dose-response analyses, consumption of fish, especially fatty types, seems generally safe at one-two servings per week and could exert protective effects.<br><br>CONCLUSIONS: Fish consumption is often associated with a variety of health outcomes, both beneficial and harmless, but only about 34% of the associations were graded as based on a moderate/high quality of evidence, and additional multicenter high quality randomized controlled trials (RCTs) with a large sample size are needed to verify these findings in the future.},
}
@article {pmid36845453,
year = {2022},
author = {Maggio, E and Alfano, A and Mete, M and Pertile, G},
title = {Intravitreal Brolucizumab for Neovascular Age-Related Macular Degeneration in a Vitrectomized Eye.},
journal = {Case reports in ophthalmology},
volume = {13},
number = {3},
pages = {736-743},
pmid = {36845453},
issn = {1663-2699},
abstract = {The efficacy of intravitreal anti-VEGF may be reduced in vitrectomized eyes due to accelerated drug clearance. Given its longer durability, brolucizumab may represent a suitable therapeutic option. However, its efficacy in vitrectomized eyes remains to be explored. Herein, we describe the management of a macular neovascularization (MNV) in a vitrectomized eye with brolucizumab after unsuccessful treatment with other anti-VEGF. A 68-year-old male was treated with pars plana vitrectomy for epiretinal membrane in his left eye (LE) in 2018. After surgery, best corrected visual acuity (BCVA) improved to 20/20 with a remarkable reduction of metamorphopsia. After 3 years, the patient returned, presenting visual loss in the LE due to MNV. He was treated with intravitreal bevacizumab injections. However, after the loading phase, an increased lesion size and exudation with worsening BCVA were detected. Therefore, the treatment was switched to aflibercept. However, after three monthly intravitreal injections, further worsening was recorded. Treatment was then switched to brolucizumab. Anatomical and functional improvement was noticed 1 month after the first brolucizumab injection. Two additional injections were performed, and further improvement was recorded with BCVA recovery to 20/20. At the last follow-up visit 2 months after the third injection, no recurrence was detected. In conclusion, determining whether anti-VEGF injections are efficacious for vitrectomized eyes would be helpful for ophthalmologists managing such patients, as well as when considering pars plana vitrectomy in eyes at risk of MNV. In our case, brolucizumab was found to be effective after unsuccessful treatment with other anti-VEGF. Additional studies are required to evaluate the safety and efficacy of brolucizumab for MNV in vitrectomized eyes.},
}
@article {pmid36843971,
year = {2023},
author = {Akpınar, &#x15e; and Köksal, E},
title = {Validity and reliability of food frequency questionnaire used in age-related eye disease studies in Turkish adults.},
journal = {Journal of nutritional science},
volume = {12},
number = {},
pages = {e20},
pmid = {36843971},
issn = {2048-6790},
mesh = {Humans ; Adult ; Reproducibility of Results ; *Antioxidants ; Turkey ; Surveys and Questionnaires ; *Eye Diseases ; },
abstract = {The present study aimed to perform the validity and reliability study of the Food Frequency Questionnaire (FFQ) on the frequency of foods rich in antioxidant nutrients and used in Age-Related Eye Diseases (AREDs). In the first interview of the study, the first application of FFQ was carried out, and blank forms of Dietary Records (DRs) were given. For the validity of the FFQ, a total of 12 d (3 days * 4 weeks) of DR were taken. For the reliability of the FFQ, a test-retest application was made with an interval of 4 weeks. The daily intake means of antioxidant nutrients, omega 3 and total antioxidant capacity data obtained from both the FFQ and DR were calculated, and the concordance between the two methods was evaluated with the Pearson Correlation Coefficient (PCC) and Bland-Altman graphs. The present study was carried out at Ege University İzmir/Turkey, Department of Ophthalmology, Retina Unit. The study was conducted with individuals aged ≥50 years who suffered from Age-Related Macular Degeneration (n 100, 72⋅0 ± 8⋅03 years). The values obtained from the test-retest applications for FFQ reliability were the same. The nutrient intake means obtained from the FFQ were similar or significantly higher than DR (P < 0⋅05). In the Bland-Altman graphical approach, the nutrient data were within the limits of agreement, and the PCCs between the two methods were moderately related. Considered together, this FFQ is a suitable tool for determining the dietary intakes of antioxidant nutrients in the Turkish population.},
}
@article {pmid36843038,
year = {2023},
author = {Scupola, A and Carlà, MM and Boselli, F and Giannuzzi, F and De Filippis, A and Fossataro, C and Minnella, AM and D'Amico, G and Coppola, G and Savastano, MC and Sammarco, MG and Rizzo, S},
title = {Brolucizumab for Wet Age-Related Macular Degeneration: One-Year Real-World Experience from a Tertiary Center.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {1},
pages = {58-67},
doi = {10.1159/000529817},
pmid = {36843038},
issn = {1423-0267},
mesh = {Humans ; *Angiogenesis Inhibitors ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; Intravitreal Injections ; Recombinant Fusion Proteins/therapeutic use ; Tomography, Optical Coherence ; },
abstract = {INTRODUCTION: The aim of this study was to explore the early efficacy and safety of treatment with intravitreal injections (IVIs) of brolucizumab in patients presenting with neovascular age-related macular degeneration (nAMD) in a real-world setting.<br><br>METHODS: This retrospective study included 194 eyes of 180 patients with nAMD treated with standard 6-mg IVIs of brolucizumab in our clinic between March 11, 2021, and June 15, 2022. Both treatment-naive (33 eyes) and switch therapy patients (161 eyes) were included in the study. Best corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid distribution (classified as intraretinal, subretinal, under the pigmented epithelium), treatment intervals, and adverse event rates were collected for analysis.<br><br>RESULTS: Average follow-up time was 37.2 &#xb1; 16.6 weeks. Mean baseline BCVAs were 38.1 &#xb1; 4.5 and 41.9 &#xb1; 6.7 letters in the treatment-naive and switch therapy groups, with a final gain of 16.0 &#xb1; 4.9 (p < 0.0001) and 10.7 &#xb1; 5.9 (p < 0.0001) letters in the two groups, respectively. Throughout the study period, CST significantly decreased in both treatment na&#xef;ve (from 352.0 &#xb1; 129.4 to 284.2 &#xb1; 93.8 &#xb5;m; p = 0.0015) and switch therapy (from 369.9 &#xb1; 140.5 to 307.4 &#xb1; 123.5 &#xb5;m; p < 0.0001). Significant fluid control rates were achieved at the end of the study period (45% and 27% eyes were completely free of fluid in na&#xef;ve and switch groups, respectively). Five eyes (2.6%) developed adverse events with different grades of intraocular inflammation and visual outcomes.<br><br>CONCLUSION: Brolucizumab IVI showed very good anatomical and functional outcomes in both naive and switch patients in this real-world experience. Nevertheless, even showing a favorable risk/benefit profile, clinicians and patients should be aware of the possibility of a small rate of severe complications.},
}
@article {pmid36839933,
year = {2023},
author = {Nishida, S and Takashima, Y and Udagawa, R and Ibaraki, H and Seta, Y and Ishihara, H},
title = {A Multifunctional Hybrid Nanocarrier for Non-Invasive siRNA Delivery to the Retina.},
journal = {Pharmaceutics},
volume = {15},
number = {2},
pages = {},
pmid = {36839933},
issn = {1999-4923},
support = {20K12652//Japan Society for the Promotion of Science/ ; },
abstract = {Drug therapy for retinal diseases (e.g., age-related macular degeneration, the leading cause of blindness) is generally performed by invasive intravitreal injection because of poor drug delivery caused by the blood-retinal barrier (BRB). This study aimed to develop a nanocarrier for the non-invasive delivery of small interfering RNA (siRNA) to the posterior segment of the eye (i.e., the retina) by eyedrops. To this end, we prepared a hybrid nanocarrier based on a multifunctional peptide and liposomes, and the composition was optimized. A cytoplasm-responsive stearylated peptide (STR-CH2R4H2C) was used as the multifunctional peptide because of its superior ability to enhance the complexation, cell permeation, and intracellular dynamics of siRNA. By adding STR-CH2R4H2C to the surface of liposomes, intracellular uptake increased regardless of the liposome surface charge. The STR-CH2R4H2C-modified cationic nanocarrier demonstrated significant siRNA transfection efficiency with no cytotoxicity, enhanced siRNA release from endosomes, and effectively suppressed vascular endothelial growth factor expression in rat retinal pigment epithelium cells. The 2.0 mol% STR-CH2R4H2C-modified cationic nanocarrier enhanced intraocular migration into the retina after instillation into rat eyes.},
}
@article {pmid36839853,
year = {2023},
author = {Schnichels, S and Simmang, D and Löscher, M and Herrmann, A and de Vries, JW and Spitzer, MS and Hurst, J},
title = {Lipid-DNA Nanoparticles as Drug-Delivery Vehicles for the Treatment of Retinal Diseases.},
journal = {Pharmaceutics},
volume = {15},
number = {2},
pages = {},
pmid = {36839853},
issn = {1999-4923},
support = {EYEnovative Research Award//Novartis Pharma GmbH/ ; E.05.00374//Intramural IZKF-Grant, University Clinics T&#xfc;bingen/ ; },
abstract = {Retinal eye diseases are the leading cause of blindness in the Western world. Up to date, the only efficient treatment for many retinal diseases consists of invasive intravitreal injections of highly concentrated drugs. Despite the fact that these injections are unpleasant for the patients, they potentially cause serious side effects, e.g., infections, bleeding within the eye or retinal detachment, especially when performed on a monthly basis, thus decreasing the injection frequency and lowering the desired drug dose. Therefore, a sustained released at the region of interest with a sustained release is desired. Recently, novel lipid-DNA nanoparticles (NPs) were shown to be an efficient drug delivery platform to the anterior segment of the eye. In this study, we investigated the distribution and tropism of the NPs when applied intravitreally, as a potential medication carrier to the posterior part of the eye. This technology is perfectly suited for the delivery of low molecular weight drugs to the back of the eye, which so far is greatly hindered by fast diffusion rates of the free drugs in the vitreous body and their intrinsically low retainability in ocular tissue. Excellent biodistribution, adherence and presence for up to five days was found for the different tested nanoparticles ex vivo and in vivo. In conclusion, our lipid-DNA based nanocarrier system was able to reach the retina within minutes and penetrate the retina providing potentially safe and long-term carrier systems for small molecules or nucleotide-based therapies.},
}
@article {pmid36839646,
year = {2023},
author = {Chadderton, N and Palfi, A and Maloney, DM and Carrigan, M and Finnegan, LK and Hanlon, KS and Shortall, C and O'Reilly, M and Humphries, P and Cassidy, L and Kenna, PF and Millington-Ward, S and Farrar, GJ},
title = {Optimisation of AAV-NDI1 Significantly Enhances Its Therapeutic Value for Correcting Retinal Mitochondrial Dysfunction.},
journal = {Pharmaceutics},
volume = {15},
number = {2},
pages = {},
pmid = {36839646},
issn = {1999-4923},
support = {16/IA/4452//Science Foundation Ireland/Ireland ; HRAPOR-2015-1140//Health Research Board/Ireland ; EI CF-2019-1106-Y//Enterprise Ireland/ ; 2008-11//Fighting Blindness/ ; MRCG-2012-4//Fighting Blindness / Health Research Charities Ireland/ ; IRC; GOIPG/2017/1631, KH 2013 and MC 2010//Irish Research Council/ ; },
abstract = {AAV gene therapy for ocular disease has become a reality with the market authorisation of Luxturna[TM] for RPE65-linked inherited retinal degenerations and many AAV gene therapies currently undergoing phase III clinical trials. Many ocular disorders have a mitochondrial involvement from primary mitochondrial disorders such as Leber hereditary optic neuropathy (LHON), predominantly due to mutations in genes encoding subunits of complex I, to Mendelian and multifactorial ocular conditions such as dominant optic atrophy, glaucoma and age-related macular degeneration. In this study, we have optimised the nuclear yeast gene, NADH-quinone oxidoreductase (NDI1), which encodes a single subunit complex I equivalent, creating a candidate gene therapy to improve mitochondrial function, independent of the genetic mutation driving disease. Optimisation of NDI1 (ophNdi1) substantially increased expression in vivo, protected RGCs and increased visual function, as assessed by optokinetic and photonegative response, in a rotenone-induced murine model. In addition, ophNdi1 increased cellular oxidative phosphorylation and ATP production and protected cells from rotenone insult to a significantly greater extent than wild type NDI1. Significantly, ophNdi1 treatment of complex I deficient patient-derived fibroblasts increased oxygen consumption and ATP production rates, demonstrating the potential of ophNdi1 as a candidate therapy for ocular disorders where mitochondrial deficits comprise an important feature.},
}
@article {pmid36839358,
year = {2023},
author = {Sahye-Pudaruth, S and Ma, DWL},
title = {Assessing the Highest Level of Evidence from Randomized Controlled Trials in Omega-3 Research.},
journal = {Nutrients},
volume = {15},
number = {4},
pages = {},
pmid = {36839358},
issn = {2072-6643},
support = {178260//Canadian Institutes of Health Research/Canada ; },
mesh = {Humans ; Randomized Controlled Trials as Topic ; *Fatty Acids, Omega-3/therapeutic use ; Dietary Supplements ; *Cardiovascular Diseases/prevention &amp; control ; Chronic Disease ; },
abstract = {Over the years, there has been heightened interest in the health benefits of n-3 polyunsaturated fatty acids (PUFA) in reducing chronic diseases such as, cardiovascular disease (CVD), cancer, type 2 diabetes, and acute macular degeneration (AMD). Due to inconsistent findings in the evidence, a review to critically examine the plethora of evidence from randomized controlled trials (RCTs) in n-3 PUFA research was undertaken. The aim of this review is to study the highest level of evidence and to identify gaps in n-3 PUFA research. RCTs were originally designed for pharmaceutical research and later adopted for nutrition and food-related research. RCTs with active diseases assume that n-3 PUFA will have "drug" like effects, and this high expectation may have led to the inconsistent evidence in the literature. The inconsistency in the literature may be related to varying doses of n-3 PUFA, sources of n-3 PUFA (food vs. supplement; plant vs. marine), type of n-3 PUFA (mixture vs. purified), trial duration, population characteristics, sample size, and genetic variation. For future research, there is a need to distinguish between primary and secondary prevention, and to focus RCTs on primary prevention of chronic diseases by n-3 PUFA which is lacking in the literature.},
}
@article {pmid36837832,
year = {2023},
author = {Ng, PQ and Saint-Geniez, M and Kim, LA and Shu, DY},
title = {Divergent Metabolomic Signatures of TGFβ2 and TNFα in the Induction of Retinal Epithelial-Mesenchymal Transition.},
journal = {Metabolites},
volume = {13},
number = {2},
pages = {},
pmid = {36837832},
issn = {2218-1989},
support = {R01 EY027739/EY/NEI NIH HHS/United States ; R01EY027739/NH/NIH HHS/United States ; },
abstract = {Epithelial-mesenchymal transition (EMT) is a dedifferentiation program in which polarized, differentiated epithelial cells lose their cell-cell adhesions and transform into matrix-producing mesenchymal cells. EMT of retinal pigment epithelial (RPE) cells plays a crucial role in many retinal diseases, including age-related macular degeneration, proliferative vitreoretinopathy, and diabetic retinopathy. This dynamic process requires complex metabolic reprogramming to accommodate the demands of this dramatic cellular transformation. Both transforming growth factor-beta 2 (TGFβ2) and tumor necrosis factor-alpha (TNFα) have the capacity to induce EMT in RPE cells; however, little is known about their impact on the RPE metabolome. Untargeted metabolomics using high-resolution mass spectrometry was performed to reveal the metabolomic signatures of cellular and secreted metabolites of primary human fetal RPE cells treated with either TGFβ2 or TNFα for 5 days. A total of 638 metabolites were detected in both samples; 188 were annotated as primary metabolites. Metabolomics profiling showed distinct metabolomic signatures associated with TGFβ2 and TNFα treatment. Enrichment pathway network analysis revealed alterations in the pentose phosphate pathway, galactose metabolism, nucleotide and pyrimidine metabolism, purine metabolism, and arginine and proline metabolism in TNFα-treated cells compared to untreated control cells, whereas TGFβ2 treatment induced perturbations in fatty acid biosynthesis metabolism, the linoleic acid pathway, and the Notch signaling pathway. These results provide a broad metabolic understanding of the bioenergetic rewiring processes governing TGFβ2- and TNFα-dependent induction of EMT. Elucidating the contributions of TGFβ2 and TNFα and their mechanistic differences in promoting EMT of RPE will enable the identification of novel biomarkers for diagnosis, management, and tailored drug development for retinal fibrotic diseases.},
}
@article {pmid36837806,
year = {2023},
author = {Shu, DY and Chaudhary, S and Cho, KS and Lennikov, A and Miller, WP and Thorn, DC and Yang, M and McKay, TB},
title = {Role of Oxidative Stress in Ocular Diseases: A Balancing Act.},
journal = {Metabolites},
volume = {13},
number = {2},
pages = {},
pmid = {36837806},
issn = {2218-1989},
support = {R01 EY019470/EY/NEI NIH HHS/United States ; R01 EY030444/EY/NEI NIH HHS/United States ; },
abstract = {Redox homeostasis is a delicate balancing act of maintaining appropriate levels of antioxidant defense mechanisms and reactive oxidizing oxygen and nitrogen species. Any disruption of this balance leads to oxidative stress, which is a key pathogenic factor in several ocular diseases. In this review, we present the current evidence for oxidative stress and mitochondrial dysfunction in conditions affecting both the anterior segment (e.g., dry eye disease, keratoconus, cataract) and posterior segment (age-related macular degeneration, proliferative vitreoretinopathy, diabetic retinopathy, glaucoma) of the human eye. We posit that further development of therapeutic interventions to promote pro-regenerative responses and maintenance of the redox balance may delay or prevent the progression of these major ocular pathologies. Continued efforts in this field will not only yield a better understanding of the molecular mechanisms underlying the pathogenesis of ocular diseases but also enable the identification of novel druggable redox targets and antioxidant therapies.},
}
@article {pmid36836923,
year = {2023},
author = {Paliwal, H and Prajapati, BG and Srichana, T and Singh, S and Patel, RJ},
title = {Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {36836923},
issn = {2075-1729},
abstract = {The number of patients with ocular disorders has increased due to contributing factors such as aging populations, environmental changes, smoking, genetic abnormalities, etc. Age-related macular degeneration (AMD) is one of the common ocular disorders which may advance to loss of vision in severe cases. The advanced form of AMD is classified into two types, dry (non-exudative) and wet (exudative) AMD. Although several therapeutic approaches are explored for the management of AMD, no approved therapy can substantially slow down the progression of dry AMD into the later stages. The focus of researchers in recent times has been engaged in developing targeted therapeutic products to halt the progression and maintain or improve vision in individuals diagnosed with AMD. The delivery of anti-VEGF agents using intravitreal therapy has found some success in managing AMD, and novel formulation approaches have been introduced in various studies to potentiate the efficacy. Some of the novel approaches, such as hydrogel, microspheres, polymeric nanoparticles, liposomes, implants, etc. have been discussed. Apart from this, subretinal, suprachoroidal, and port delivery systems have also been investigated for biologics and gene therapies. The unmet potential of approved therapeutic products has contributed to several patent applications in recent years. This review outlines the current treatment options, outcomes of recent research studies, and patent details around the novel drug delivery approach for the treatment of AMD.},
}
@article {pmid36836742,
year = {2023},
author = {Onwuka, O and Saddemi, JL and Akkan Aydoğmuş, FS and Lasalle, CC and Ramsey, DJ},
title = {Consequences of Real-World Surveillance of Fellow Eyes in Neovascular Age-Related Macular Degeneration.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {36836742},
issn = {2075-1729},
abstract = {This study investigated whether the interval of monitoring at-risk, fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) has any bearing on the severity of the disease at the time of diagnosis. The study comprised a retrospective, cross-sectional comparative case series of treatment-naïve eyes in patients who were diagnosed sequentially with nAMD. We compared the visual acuity (VA) and central macular thickness (CMT) of patients who were actively receiving intravitreal injections (IVIs) of anti-vascular endothelial growth factor (anti-VEGF) agents at the time of second eye diagnosis with the VA and CMT of patients who had ceased treatment in their first eye because of reaching end-stages of disease. Intervals of visits and frequency of monitoring the macula of fellow eyes by means of optical coherence tomography (OCT) were abstracted from the medical record. We found that the at-risk fellow eyes of patients who had stopped treatment for nAMD in their first eye prior to fellow eye conversion were monitored significantly less frequently than the fellow eyes of patients who continued to receive treatment at the time of second eye diagnosis. Despite less frequent monitoring, VA and CMT were similar at the time of fellow eye diagnosis for both groups.},
}
@article {pmid36836210,
year = {2023},
author = {Wu, T and Wei, X and Dang, K and Tao, M and Lv, B and Chen, T and Zhang, Z and Zhou, J and Du, H},
title = {Liver X Receptor Agonist Inhibits Oxidized Low-Density Lipoprotein Induced Choroidal Neovascularization via the NF-κB Signaling Pathway.},
journal = {Journal of clinical medicine},
volume = {12},
number = {4},
pages = {},
pmid = {36836210},
issn = {2077-0383},
support = {81470654//National Natural Science Foundation of China/ ; 2019SF-047//Natural Science Foundation of Shaanxi Province/ ; },
abstract = {Age-related macular degeneration (AMD) is the most common blindness-causing disease among the elderly. Under oxidative stress, low-density lipoprotein in the outer layer of the retina is easily converted into oxidized low-density lipoprotein (OxLDL), which promotes the development of choroidal neovascularization (CNV), the main pathological change in wet AMD. Liver X receptor (LXR), a ligand-activated nuclear transcription factor, regulates various processes related to CNV, including lipid metabolism, cholesterol transport, inflammation, and angiogenesis. In this study, we evaluated the effects of the LXR agonist TO901317 (TO) on CNV. Our results demonstrated that the TO could inhibit OxLDL-induced CNV in mice as well as inflammation and angiogenesis in vitro. Using siRNA transfection in cells and Vldlr[-/-] mice, we further confirmed the inhibitory effects of TO against the inflammatory response and oxidative stress. Mechanistically, the LXR agonist reduces the inflammatory response via the nuclear translocation of NF-κB p65 in the pathway for NF-κB activation and by enhancing ABCG1-dependent lipid transportation. Therefore, an LXR agonist is a promising therapeutic candidate for AMD, especially for wet AMD.},
}
@article {pmid36836125,
year = {2023},
author = {Korb, CA and Beck, S and Wolters, D and Lorenz, K and Pfeiffer, N and Grus, FH},
title = {Serum Autoantibodies in Patients with Dry and Wet Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {4},
pages = {},
pmid = {36836125},
issn = {2077-0383},
support = {n.a.//Novartis Pharma GmbH, Germany/ ; },
abstract = {BACKGROUND: To assess the serum autoantibody profile in patients with dry and exudative age-related macular degeneration compared with healthy volunteers to detect potential biomarkers, e.g., markers for progression of the disease.<br><br>MATERIALS AND METHODS: IgG Immunoreactivities were compared in patients suffering from dry age-related macular degeneration (AMD) (n = 20), patients with treatment-naive exudative AMD (n = 29) and healthy volunteers (n = 21). Serum was analysed by customized antigen microarrays containing 61 antigens. The statistical analysis was performed by univariate and multivariate analysis of variance, predictive data-mining methods and artificial neuronal networks were used to detect specific autoantibody patterns.<br><br>RESULTS: The immunoreactivities of dry and wet AMD patients were significantly different from each other and from controls. One of the most prominently changed reactivity was against alpha-synuclein (p &#x2264; 0.0034), which is known from other neurodegenerative diseases. Furthermore, reactivities against glyceraldehyde-3-phosphat-dehydrogenase (p &#x2264; 0.031) and Annexin V (p &#x2264; 0.034), which performs a major role in apoptotic processes, were significantly changed. Some immunoreacitvities were antithetic regulated in wet and dry-AMD, such as Vesicle transport-related protein (VTI-B).<br><br>CONCLUSIONS: Comparison of autoantibody profiles in patients with dry and wet AMD revealed significantly altered immunoreactivities against proteins particularly found in immunological diseases, further neurodegenerative, apoptotic and autoimmune markers could be observed. A validation study has to explore if these antibody pattern can help to understand the underlying differences in pathogenesis, evaluate their prognostic value and if those could be possibly useful as additional therapeutic targets.},
}
@article {pmid36835897,
year = {2023},
author = {Nagai, N and Mushiga, Y and Ozawa, Y},
title = {Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes.},
journal = {Journal of clinical medicine},
volume = {12},
number = {4},
pages = {},
pmid = {36835897},
issn = {2077-0383},
support = {22K09799 and 21K09683//JSPS KAKENHI/ ; },
abstract = {Choriocapillaris flow deficits detected on optical coherence tomography angiographs were retrospectively analyzed. In 38 age-related macular degeneration (AMD) fellow eyes, without fundus findings (26 men, 71.7 ± 1.9 years old), and 22 control eyes (11 men, 69.4 ± 1.8), the choriocapillaris flow area (CCFA) ratio and coefficient of variation (CV) of the CCFA ratio (which represented the heterogeneity of the ratio), negatively and positively correlated with age (all p < 0.01), respectively. Moreover, the respective mean values were lower (p = 0.0031) and greater (p = 0.002) in AMD fellow eyes than in the control eyes. The high-risk condition of AMD fellow eyes was defined by a CCFA ratio <58.5%, and the CV of the CCFA ratio ≥0.165 (odds ratio (OR), 5.408; 95% confidence interval (CI): 1.117-21.118, p = 0.035, after adjusting for age and sex) was related to the presence of fundus autofluorescence abnormality (OR, 16.440; 95% CI, 1.262-214.240; p = 0.033) and asymmetrically dilated choroidal large vasculature (OR, 4.176; 95% CI, 1.057-16.503; p = 0.042), after adjusting for age and sex. The presence of fundus autofluorescence abnormality indicated a retinal pigment epithelium (RPE) abnormality. The RPE volume was reduced in the latter eye group, particularly in the thinner choroidal vasculature. In addition to aging, RPE abnormality and choroidal large vascular flow imbalances were associated with exacerbated heterogeneous choriocapillaris flow deficits in AMD fellow eyes without macular neovascularization.},
}
@article {pmid36835325,
year = {2023},
author = {Sohn, J and Lee, SE and Shim, EY},
title = {DNA Damage and Repair in Eye Diseases.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36835325},
issn = {1422-0067},
support = {R01 GM141631/GM/NIGMS NIH HHS/United States ; R21 ES031772/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/complications ; *Eye Diseases ; *Glaucoma/complications ; *Cataract ; Blindness ; DNA Damage ; },
abstract = {Vision is vital for daily activities, and yet the most common eye diseases-cataracts, DR, ARMD, and glaucoma-lead to blindness in aging eyes. Cataract surgery is one of the most frequently performed surgeries, and the outcome is typically excellent if there is no concomitant pathology present in the visual pathway. In contrast, patients with DR, ARMD and glaucoma often develop significant visual impairment. These often-multifactorial eye problems can have genetic and hereditary components, with recent data supporting the role of DNA damage and repair as significant pathogenic factors. In this article, we discuss the role of DNA damage and the repair deficit in the development of DR, ARMD and glaucoma.},
}
@article {pmid36835257,
year = {2023},
author = {Millington-Ward, S and Chadderton, N and Finnegan, LK and Post, IJM and Carrigan, M and Nixon, R and Humphries, MM and Humphries, P and Kenna, PF and Palfi, A and Farrar, GJ},
title = {RPE-Directed Gene Therapy Improves Mitochondrial Function in Murine Dry AMD Models.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36835257},
issn = {1422-0067},
support = {16/IA/4452/SFI_/Science Foundation Ireland/Ireland ; EI CF-2019-1106-Y//Enterprise Ireland/ ; HRAPOR-2015-1140//Health Research Board Ireland/ ; StarT 813490//EU Marie Curie Innovative Training Network/ ; MRCG-2016-14//Fighting Blindness Ireland - Health Research Charities Ireland/ ; },
mesh = {Aged ; Animals ; Humans ; Mice ; Electron Transport Complex I/metabolism ; *Genetic Therapy/methods ; *Geographic Atrophy/genetics/therapy ; Mitochondria/metabolism ; Retinal Pigment Epithelium/metabolism ; *Saccharomyces cerevisiae Proteins/genetics ; },
abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness in the aged population. However, to date there is no effective treatment for the dry form of the disease, representing 85-90% of cases. AMD is an immensely complex disease which affects, amongst others, both retinal pigment epithelium (RPE) and photoreceptor cells and leads to the progressive loss of central vision. Mitochondrial dysfunction in both RPE and photoreceptor cells is emerging as a key player in the disease. There are indications that during disease progression, the RPE is first impaired and RPE dysfunction in turn leads to subsequent photoreceptor cell degeneration; however, the exact sequence of events has not as yet been fully determined. We recently showed that AAV delivery of an optimised NADH-ubiquinone oxidoreductase (NDI1) gene, a nuclear-encoded complex 1 equivalent from S. cerevisiae, expressed from a general promoter, provided robust benefit in a variety of murine and cellular models of dry AMD; this was the first study employing a gene therapy to directly boost mitochondrial function, providing functional benefit in vivo. However, use of a restricted RPE-specific promoter to drive expression of the gene therapy enables exploration of the optimal target retinal cell type for dry AMD therapies. Furthermore, such restricted transgene expression could reduce potential off-target effects, possibly improving the safety profile of the therapy. Therefore, in the current study, we interrogate whether expression of the gene therapy from the RPE-specific promoter, Vitelliform macular dystrophy 2 (VMD2), might be sufficient to rescue dry AMD models.},
}
@article {pmid36834828,
year = {2023},
author = {Wang, JH and Urrutia-Cabrera, D and Lees, JG and Mesa Mora, S and Nguyen, T and Hung, SSC and Hewitt, AW and Lim, SY and Edwards, TL and Wong, RCB},
title = {Development of a CRISPRi Human Retinal Pigmented Epithelium Model for Functional Study of Age-Related Macular Degeneration Genes.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36834828},
issn = {1422-0067},
support = {N/A//Centre for Eye Research Australia/ ; N/A//University of Melbourne/ ; N/A//Stafford Fox Medical Research Foundation/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; Clustered Regularly Interspaced Short Palindromic Repeats ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/metabolism ; Oxidative Stress ; Epithelium/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a blinding disease characterised by dysfunction of the retinal pigmented epithelium (RPE) which culminates in disruption or loss of the neurosensory retina. Genome-wide association studies have identified >60 genetic risk factors for AMD; however, the expression profile and functional role of many of these genes remain elusive in human RPE. To facilitate functional studies of AMD-associated genes, we developed a human RPE model with integrated CRISPR interference (CRISPRi) for gene repression by generating a stable ARPE19 cell line expressing dCas9-KRAB. We performed transcriptomic analysis of the human retina to prioritise AMD-associated genes and selected TMEM97 as a candidate gene for knockdown study. Using specific sgRNAs, we showed that knockdown of TMEM97 in ARPE19 reduced reactive oxygen species (ROS) levels and exerted a protective effect against oxidative stress-induced cell death. This work provides the first functional study of TMEM97 in RPE and supports a potential role of TMEM97 in AMD pathobiology. Our study highlights the potential for using CRISPRi to study AMD genetics, and the CRISPRi RPE platform generated here provided a useful in vitro tool for functional studies of AMD-associated genes.},
}
@article {pmid36834668,
year = {2023},
author = {Shen, S and Kapphahn, RJ and Zhang, M and Qian, S and Montezuma, SR and Shang, P and Ferrington, DA and Qu, J},
title = {Quantitative Proteomics of Human Retinal Pigment Epithelium Reveals Key Regulators for the Pathogenesis of Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36834668},
issn = {1422-0067},
support = {EY028554/NH/NIH HHS/United States ; R01 EY026012/EY/NEI NIH HHS/United States ; R01 EY028554/EY/NEI NIH HHS/United States ; EY026012/NH/NIH HHS/United States ; U01 EY034669/EY/NEI NIH HHS/United States ; EY034669/NH/NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Retinal Pigment Epithelium/metabolism ; Proteomics ; Reproducibility of Results ; *Macular Degeneration/metabolism ; Oxidative Stress ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people, with limited treatment options available for most patients. AMD involves the death of retinal pigment epithelium (RPE) and photoreceptor cells, with mitochondria dysfunction being a critical early event. In the current study, we utilized our unique resource of human donor RPE graded for AMD presence and severity to investigate proteome-wide dysregulation involved in early AMD. Organelle-enriched fractions of RPE were isolated from donors with early AMD (n = 45) and healthy age-matched controls (n = 32) and were analyzed by UHR-IonStar, an integrated proteomics platform enabling reliable and in-depth proteomic quantification in large cohorts. A total of 5941 proteins were quantified with excellent analytical reproducibility, and with further informatics analysis, many biological functions and pathways were found to be significantly dysregulated in donor RPE samples with early AMD. Several of these directly pinpointed changes in mitochondrial functions, e.g., translation, ATP metabolic process, lipid homeostasis, and oxidative stress. These novel findings highlighted the value of our proteomics investigation by allowing a better understanding of the molecular mechanisms underlying early AMD onset and facilitating both treatment development and biomarker discovery.},
}
@article {pmid36834287,
year = {2023},
author = {Kamińska, A and Pinkas, J and Wrześniewska-Wal, I and Ostrowski, J and Jankowski, M},
title = {Awareness of Common Eye Diseases and Their Risk Factors-A Nationwide Cross-Sectional Survey among Adults in Poland.},
journal = {International journal of environmental research and public health},
volume = {20},
number = {4},
pages = {},
pmid = {36834287},
issn = {1660-4601},
mesh = {Adult ; Humans ; Cross-Sectional Studies ; Poland ; Surveys and Questionnaires ; Health Knowledge, Attitudes, Practice ; *Eye Diseases/complications ; *Glaucoma/complications ; Risk Factors ; },
abstract = {Public knowledge and awareness of eye diseases may influence individuals' behaviors toward the use of eye care services and prevention methods. The objective of this study was to assess the awareness of common eye diseases and their risk factors among adults in Poland as well as to identify factors associated with knowledge of eye diseases. This nationwide cross-sectional web-based survey was carried out in December 2022 on a representative sample of 1076 adults in Poland. Most of the respondents had heard of cataracts (83.6%), glaucoma (80.7%), conjunctivitis (74.3%), and hordeolum (73.8%). Awareness of dry eye syndrome was declared by 50% of respondents, and 40% were aware of retinal detachment. Among the respondents, 32.3% had heard of AMD, and 16.4% had heard of diabetic retinopathy. A lack of awareness of glaucoma was declared by 38.1% of respondents, and 54.3% declared a lack of awareness of risk factors for AMD. Gender, age, and the presence of chronic diseases were the most important factors (p < 0.05) associated with awareness of common eye diseases and risk factors for glaucoma and AMD. This study demonstrated a low level of awareness of common eye diseases among adults in Poland. Personalized communication on eye diseases is needed.},
}
@article {pmid36833344,
year = {2023},
author = {Moore, SM and Christoforidis, JB},
title = {Advances in Ophthalmic Epigenetics and Implications for Epigenetic Therapies: A Review.},
journal = {Genes},
volume = {14},
number = {2},
pages = {},
pmid = {36833344},
issn = {2073-4425},
mesh = {Animals ; Retina/pathology ; *Retinal Degeneration/pathology ; *Macular Degeneration/pathology ; Retinal Ganglion Cells/pathology ; Epigenesis, Genetic ; },
abstract = {The epigenome represents a vast molecular apparatus that writes, reads, and erases chemical modifications to the DNA and histone code without changing the DNA base-pair sequence itself. Recent advances in molecular sequencing technology have revealed that epigenetic chromatin marks directly mediate critical events in retinal development, aging, and degeneration. Epigenetic signaling regulates retinal progenitor (RPC) cell cycle exit during retinal laminar development, giving rise to retinal ganglion cells (RGCs), amacrine cells, horizontal cells, bipolar cells, photoreceptors, and Müller glia. Age-related epigenetic changes such as DNA methylation in the retina and optic nerve are accelerated in pathogenic conditions such as glaucoma and macular degeneration, but reversing these epigenetic marks may represent a novel therapeutic target. Epigenetic writers also integrate environmental signals such as hypoxia, inflammation, and hyperglycemia in complex retinal conditions such as diabetic retinopathy (DR) and choroidal neovascularization (CNV). Histone deacetylase (HDAC) inhibitors protect against apoptosis and photoreceptor degeneration in animal models of retinitis pigmentosa (RP). The epigenome represents an intriguing therapeutic target for age-, genetic-, and neovascular-related retinal diseases, though more work is needed before advancement to clinical trials.},
}
@article {pmid36832215,
year = {2023},
author = {Liew, A and Agaian, S and Benbelkacem, S},
title = {Distinctions between Choroidal Neovascularization and Age Macular Degeneration in Ocular Disease Predictions via Multi-Size Kernels ξcho-Weighted Median Patterns.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
pmid = {36832215},
issn = {2075-4418},
abstract = {Age-related macular degeneration is a visual disorder caused by abnormalities in a part of the eye's retina and is a leading source of blindness. The correct detection, precise location, classification, and diagnosis of choroidal neovascularization (CNV) may be challenging if the lesion is small or if Optical Coherence Tomography (OCT) images are degraded by projection and motion. This paper aims to develop an automated quantification and classification system for CNV in neovascular age-related macular degeneration using OCT angiography images. OCT angiography is a non-invasive imaging tool that visualizes retinal and choroidal physiological and pathological vascularization. The presented system is based on new retinal layers in the OCT image-specific macular diseases feature extractor, including Multi-Size Kernels ξcho-Weighted Median Patterns (MSKξMP). Computer simulations show that the proposed method: (i) outperforms current state-of-the-art methods, including deep learning techniques; and (ii) achieves an overall accuracy of 99% using ten-fold cross-validation on the Duke University dataset and over 96% on the noisy Noor Eye Hospital dataset. In addition, MSKξMP performs well in binary eye disease classifications and is more accurate than recent works in image texture descriptors.},
}
@article {pmid36831285,
year = {2023},
author = {Moustardas, P and Aberdam, D and Lagali, N},
title = {MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges.},
journal = {Cells},
volume = {12},
number = {4},
pages = {},
pmid = {36831285},
issn = {2073-4409},
mesh = {*Mitogen-Activated Protein Kinases/metabolism ; *p38 Mitogen-Activated Protein Kinases/metabolism ; Signal Transduction ; Phosphorylation ; MAP Kinase Signaling System/physiology ; },
abstract = {Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors.},
}
@article {pmid36831096,
year = {2023},
author = {Chandra, S and Grewal, MK and Gurudas, S and Sondh, R and Bird, A and Jeffery, G and Chong, V and Sivaprasad, S},
title = {Quantitative Autofluorescence in Non-Neovascular Age Related Macular Degeneration.},
journal = {Biomedicines},
volume = {11},
number = {2},
pages = {},
pmid = {36831096},
issn = {2227-9059},
support = {1905//Fight for Sight/ ; },
abstract = {Quantitative autofluorescence (qAF8) level is a presumed surrogate marker of lipofuscin content in the retina. We investigated the changes in the qAF8 levels in non-neovascular AMD. In this prospective cohort study, Caucasians aged ≥50 years with varying severity of non-neovascular AMD in at least one eye and Snellen visual acuity ≥6/18 were recruited. The qAF8 levels were analysed in the middle eight segments of the Delori pattern (HEYEX software, Heidelberg, Germany). The AMD categories were graded using both the Beckman classification and multimodal imaging (MMI) to include the presence of subretinal drusenoid deposits (SDD). A total of 353 eyes from 231 participants were analyzed. Compared with the age-matched controls, the qAF8 values decreased in the eyes with AMD (adjusted % difference = -19.7% [95% CI -28.8%, -10.4%]; p < 0.001) and across the AMD categories, (adjusted % differences; Early, -13.1% (-24.4%, -1%), p = 0.04; intermediate AMD (iAMD), -22.9% (-32.3%, -13.1%), p < 0.001; geographic atrophy -25.2% (-38.1%, -10.4%), p = 0.002). On MMI, the qAF8 was reduced in the AMD subgroups relative to the controls, (adjusted % differences; Early, -5.8% (-18.9%, 8.3%); p = 0.40; iAMD, -26.7% (-36.2%, -15.6%); p < 0.001; SDD, -23.7% (-33.6%, -12.2%); p < 0.001; atrophy, -26.7% (-39.3%, -11.3%), p = 0.001). The qAF8 levels declined early in AMD and were not significantly different between the severity levels of non-neovascular AMD, suggesting the early and sustained loss of function of the retinal pigment epithelium in AMD.},
}
@article {pmid36830932,
year = {2023},
author = {Zhdankina, AA and Tikhonov, DI and Logvinov, SV and Plotnikov, MB and Khlebnikov, AI and Kolosova, NG},
title = {Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S.},
journal = {Biomedicines},
volume = {11},
number = {2},
pages = {},
pmid = {36830932},
issn = {2227-9059},
support = {22-25-00686//Russian Science Foundation/ ; without number//Tomsk Polytechnic University Development Program/ ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. The development of AMD is associated with inflammation, oxidative stress, and progressive proteostasis imbalance, in the regulation of which c-Jun N-terminal kinases (JNK) play a crucial role. JNK inhibition is discussed as an alternative way for prevention and treatment of AMD and other neurodegenerative diseases. Here we assess the retinoprotective potential of the recently synthesized JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S) using senescence-accelerated OXYS rats as a model of AMD. The treatment with IQ-1S (50 mg/kg body weight intragastric) during the period of active disease development (from 4.5 to 6 months of age) improved some (but not all) histological abnormalities associated with retinopathy. IQ-1S improved blood circulation, increased the functional activity of the retinal pigment epithelium, reduced the VEGF expression in the endothelial cells, and increased the expression of PEDF in the neuroretina. The result was a decrease in the degeneration of photoreceptors and neurons of the inner layers. IQ-1S significantly improved the retinal ultrastructure and increased the number of mitochondria, which were significantly reduced in the neuroretina of OXYS rats compared to Wistar rats. It seems probable that using IQ-1S can be a good prophylactic strategy to treat AMD.},
}
@article {pmid36830851,
year = {2023},
author = {Gupta, S and Lytvynchuk, L and Ardan, T and Studenovska, H and Faura, G and Eide, L and Znaor, L and Erceg, S and Stieger, K and Motlik, J and Bharti, K and Petrovski, G},
title = {Retinal Pigment Epithelium Cell Development: Extrapolating Basic Biology to Stem Cell Research.},
journal = {Biomedicines},
volume = {11},
number = {2},
pages = {},
pmid = {36830851},
issn = {2227-9059},
abstract = {The retinal pigment epithelium (RPE) forms an important cellular monolayer, which contributes to the normal physiology of the eye. Damage to the RPE leads to the development of degenerative diseases, such as age-related macular degeneration (AMD). Apart from acting as a physical barrier between the retina and choroidal blood vessels, the RPE is crucial in maintaining photoreceptor (PR) and visual functions. Current clinical intervention to treat early stages of AMD includes stem cell-derived RPE transplantation, which is still in its early stages of evolution. Therefore, it becomes essential to derive RPEs which are functional and exhibit features as observed in native human RPE cells. The conventional strategy is to use the knowledge obtained from developmental studies using various animal models and stem cell-based exploratory studies to understand RPE biogenies and developmental trajectory. This article emphasises such studies and aims to present a comprehensive understanding of the basic biology, including the genetics and molecular pathways of RPE development. It encompasses basic developmental biology and stem cell-based developmental studies to uncover RPE differentiation. Knowledge of the in utero developmental cues provides an inclusive methodology required for deriving RPEs using stem cells.},
}
@article {pmid36830838,
year = {2023},
author = {Josifovska, N and Andjelic, S and Lytvynchuk, L and Lumi, X and Dučić, T and Petrovski, G},
title = {Biomacromolecular Profile in Human Primary Retinal Pigment Epithelial Cells-A Study of Oxidative Stress and Autophagy by Synchrotron-Based FTIR Microspectroscopy.},
journal = {Biomedicines},
volume = {11},
number = {2},
pages = {},
pmid = {36830838},
issn = {2227-9059},
abstract = {Synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy is a non-destructive and chemically sensitive technique for the rapid detection of changes in the different components of the cell's biomacromolecular profile. Reactive oxygen species and oxidative stress may cause damage to the DNA, RNA, and proteins in the retinal pigment epithelium (RPE), which can further lead to age-related macular degeneration (AMD) and visual loss in the elderly. In this study, human primary RPEs (hRPEs) were used to study AMD pathogenesis by using an established in vitro cellular model of the disease. Autophagy-a mechanism of intracellular degradation, which is altered during AMD, was studied in the hRPEs by using the autophagy inducer rapamycin and treated with the autophagy inhibitor bafilomycin A1. In addition, oxidative stress was induced by the hydrogen peroxide (H2O2) treatment of hRPEs. By using SR-FTIR microspectroscopy and multivariate analyses, the changes in the phosphate groups of nucleic acids, Amide I and II of the proteins, the carbonyl groups, and the lipid status in the hRPEs showed a significantly different pattern under oxidative stress/autophagy induction and inhibition. This biomolecular fingerprint can be evaluated in future drug discovery studies affecting autophagy and oxidative stress in AMD.},
}
@article {pmid36830076,
year = {2023},
author = {Mohtashami, Z and Singh, MK and Neto, FT and Salimiaghdam, N and Hasanpour, H and Kenney, MC},
title = {Mitochondrial Open Reading Frame of the 12S rRNA Type-c: Potential Therapeutic Candidate in Retinal Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {36830076},
issn = {2076-3921},
abstract = {Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is the most unearthed peptide encoded by mitochondrial DNA (mtDNA). It is an important regulator of the nuclear genome during times of stress because it promotes an adaptive stress response to maintain cellular homeostasis. Identifying MOTS-c specific binding partners may aid in deciphering the complex web of mitochondrial and nuclear-encoded signals. Mitochondrial damage and dysfunction have been linked to aging and the accelerated cell death associated with many types of retinal degenerations. Furthermore, research on MOTS-c ability to revive oxidatively stressed RPE cells has revealed a significant protective role for the molecule. Evidence suggests that senescent cells play a role in the development of age-related retinal disorders. This review examines the links between MOTS-c, mitochondria, and age-related diseases of the retina. Moreover, the untapped potential of MOTS-c as a treatment for glaucoma, diabetic retinopathy, and age-related macular degeneration is reviewed.},
}
@article {pmid36829973,
year = {2023},
author = {Semenov, AN and Maksimov, EG and Moysenovich, AM and Yakovleva, MA and Tsoraev, GV and Ramonova, AA and Shirshin, EA and Sluchanko, NN and Feldman, TB and Rubin, AB and Kirpichnikov, MP and Ostrovsky, MA},
title = {Protein-Mediated Carotenoid Delivery Suppresses the Photoinducible Oxidation of Lipofuscin in Retinal Pigment Epithelial Cells.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {36829973},
issn = {2076-3921},
support = {22-25-00183//Russian Science Foundation/ ; },
abstract = {Lipofuscin of retinal pigment epithelium (RPE) cells is a complex heterogeneous system of chromophores which accumulates as granules during the cell's lifespan. Lipofuscin serves as a source of various cytotoxic effects linked with oxidative stress. Several age-related eye diseases such as macular degeneration of the retina, as well as some severe inherited eye pathologies, are accompanied by a significant increase in lipofuscin granule concentration. The accumulation of carotenoids in the RPE could provide an effective antioxidant protection against lipofuscin cytotoxic manifestations. Given the highly lipophilic nature of carotenoids, their targeted delivery to the vulnerable tissues can potentially be assisted by special proteins. In this study, we demonstrate how protein-mediated delivery of zeaxanthin using water-soluble Bombyx mori carotenoid-binding protein (BmCBP-ZEA) suppresses the photoinducible oxidative stress in RPE cells caused by irradiation of lipofuscin with intense white light. We implemented fluorescence lifetime imaging of the RPE cell culture ARPE-19 fed with lipofuscin granules and then irradiated by white light with and without the addition of BmCBP-ZEA. We demonstrate that after irradiation the mean fluorescence lifetime of lipofuscin significantly increases, while the presence of BmCBP-ZEA at 200 nM concentration suppresses the increase in the average lifetime of lipofuscin fluorescence, indicating an approx. 35% inhibition of the oxidative stress. This phenomenon serves as indirect yet important evidence of the efficiency of the protein-mediated carotenoid delivery into pigment epithelium cells.},
}
@article {pmid36829938,
year = {2023},
author = {Ramos Rego, I and Silvério, D and Eufrásio, MI and Pinhanços, SS and Lopes da Costa, B and Teixeira, J and Fernandes, H and Kong, Y and Li, Y and Tsang, SH and Oliveira, PJ and Fernandes, R and Quinn, PMJ and Santos, PF and Ambrósio, AF and Alves, CH},
title = {TRAP1 Is Expressed in Human Retinal Pigment Epithelial Cells and Is Required to Maintain their Energetic Status.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {36829938},
issn = {2076-3921},
support = {R01 EY018213/EY/NEI NIH HHS/United States ; U01 EY030580/EY/NEI NIH HHS/United States ; R01 EY026682/EY/NEI NIH HHS/United States ; R01 EY033770/EY/NEI NIH HHS/United States ; R24 EY027285/EY/NEI NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; R01 EY024698/EY/NEI NIH HHS/United States ; P30 EY019007/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of severe vision loss and blindness in elderly people worldwide. The damage to the retinal pigment epithelium (RPE) triggered by oxidative stress plays a central role in the onset and progression of AMD and results from the excessive accumulation of reactive oxygen species (ROS) produced mainly by mitochondria. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecular chaperone that contributes to the maintenance of mitochondrial integrity by decreasing the production and accumulation of ROS. The present study aimed to evaluate the presence and the role of TRAP1 in the RPE. Here, we report that TRAP1 is expressed in human adult retinal pigment epithelial cells and is located mainly in the mitochondria. Exposure of RPE cells to hydrogen peroxide decreases the levels of TRAP1. Furthermore, TRAP1 silencing increases intracellular ROS production and decreases mitochondrial respiratory capacity without affecting cell proliferation. Together, these findings offer novel insights into TRAP1 functions in RPE cells, opening possibilities to develop new treatment options for AMD.},
}
@article {pmid36829888,
year = {2023},
author = {Lee, SJ and Roh, YJ and Kim, JE and Jin, YJ and Song, HJ and Seol, A and Park, SH and Douangdeuane, B and Souliya, O and Choi, SI and Hwang, DY},
title = {Protective Effects of Dipterocarpus tuberculatus in Blue Light-Induced Macular Degeneration in A2E-Laden ARPE19 Cells and Retina of Balb/c Mice.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {36829888},
issn = {2076-3921},
support = {F21YY8109033//National Research Foundation of Korea/ ; F22YY8109033//National Research Foundation of Korea/ ; },
abstract = {Natural products with significant antioxidant activity have been receiving attention as one of the treatment strategies to prevent age-related macular degeneration (AMD). Reactive oxygen intermediates (ROI) including oxo-N-retinylidene-N-retinylethanolamine (oxo-A2E) and singlet oxygen-induced damage, are believed to be one of the major causes of the development of AMD. To investigate the therapeutic effects of methanol extracts of Dipterocarpus tuberculatus Roxb. (MED) against blue light (BL)-caused macular degeneration, alterations in the antioxidant activity, apoptosis pathway, neovascularization, inflammatory response, and retinal degeneration were analyzed in A2E-laden ARPE19 cells and Balb/c mice after exposure of BL. Seven bioactive components, including 2α-hydroxyursolic acid, ε-viniferin, asiatic acid, bergenin, ellagic acid, gallic acid and oleanolic acid, were detected in MED. MED exhibited high DPPH and ABTS free radical scavenging activity. BL-induced increases in intracellular reactive oxygen species (ROS) production and nitric oxide (NO) concentration were suppressed by MED treatment. A significant recovery of antioxidant capacity by an increase in superoxide dismutase enzyme (SOD) activity, SOD expression levels, and nuclear factor erythroid 2-related factor 2 (NRF2) expression were detected as results of MED treatment effects. The activation of the apoptosis pathway, the expression of neovascular proteins, cyclooxygenase-2 (COX-2)-induced inducible nitric oxide synthase (iNOS) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was remarkably inhibited in the MED treated group compared to the Vehicle-treated group in the AMD cell model. Furthermore, MED displayed protective effects in BL-induced retinal degeneration through improvement in the thickness of the whole retina, outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) in Balb/c mice. Taken together, these results indicate that MED exhibits protective effects in BL-induced retinal degeneration and has the potential in the future to be developed as a treatment option for dry AMD with atrophy of retinal pigment epithelial (RPE) cells.},
}
@article {pmid36828853,
year = {2023},
author = {Matsumoto, H and Hoshino, J and Nakamura, K and Akiyama, H},
title = {Two-year outcomes of treat-and-extend regimen with intravitreal brolucizumab for treatment-naïve neovascular age-related macular degeneration with type 1 macular neovascularization.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {3249},
pmid = {36828853},
issn = {2045-2322},
mesh = {Humans ; Follow-Up Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Tomography, Optical Coherence ; Intravitreal Injections ; Neovascularization, Pathologic/drug therapy ; *Macular Degeneration/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; *Wet Macular Degeneration/drug therapy ; },
abstract = {We previously reported one-year results of a treat-and-extend (TAE) regimen with intravitreal brolucizumab for 68 eyes with treatment-naïve neovascular age-related macular degeneration (nAMD) associated with type 1 macular neovascularization (MNV). In the current study, we evaluated second-year results of the brolucizumab TAE therapy in 45 eyes with type 1 MNV that had completed the first-year treatment. Forty-three eyes (95.6%) received brolucizumab TAE treatment during a period of 96 weeks. The significant improvement of best-corrected visual acuity in the first year was maintained in the second year. Moreover, the significant foveal thickness and central choroidal thickness reductions in the first year were maintained in the second year. The total number of injections over the 96-week study period was 10.0 ± 1.4, with 6.4 ± 0.6 in the first year and 3.6 ± 1.0 in the second year. The intended injection interval at week 96 was 8 weeks in 9 eyes (20.9%), 12 weeks in 3 eyes (7.0%), and 16 weeks in 31 eyes (72.1%), with an average injection interval of 14.0 ± 3.3 weeks. No eyes developed brolucizumab-related intraocular inflammation (IOI) during the second-year treatment. These results indicate that the TAE regimen with intravitreal brolucizumab for treatment-naïve nAMD associated with type 1 MNV effectively maintained the improved visual acuity and the diminished exudative changes in the second year. Moreover, intravitreal brolucizumab has the potential to reduce the treatment burden of nAMD. The risk of developing brolucizumab-related IOI appeared to be very low during the second year of this TAE regimen.},
}
@article {pmid36826465,
year = {2023},
author = {Hsu, SC and Feng, SH and Pan, SL},
title = {Risk of developing age-related macular degeneration in patients with osteoporosis: a population-based, longitudinal follow-up study.},
journal = {Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA},
volume = {34},
number = {4},
pages = {793-801},
pmid = {36826465},
issn = {1433-2965},
mesh = {Male ; Humans ; Female ; Follow-Up Studies ; Retrospective Studies ; *Macular Degeneration/complications/epidemiology ; *Osteoporosis/complications/epidemiology ; Proportional Hazards Models ; Risk Factors ; Incidence ; },
abstract = {UNLABELLED: Osteoporosis was suggested to be associated with higher odds of age-related macular degeneration. However, the temporal relationship between osteoporosis and age-related macular degeneration has not been explored. This population-based longitudinal follow-up study showed an increased risk of age-related macular degeneration in both men and women with osteoporosis.<br><br>PURPOSE: To investigate the long-term risk of age-related macular degeneration (AMD) in patients with osteoporosis.<br><br>METHODS: This is a retrospective cohort study using the Longitudinal Health Insurance Database 2005, a subset of Taiwan's National Health Insurance research database. A total of 23,611 individuals aged 50 to 79 who were diagnosed with osteoporosis between January 1, 2002 and December 31, 2006, were enrolled in the osteoporosis group. An exactly equal number of propensity score-matched individuals without osteoporosis comprised the comparison group. The variables used in propensity score matching included age, sex, comorbidities, and socioeconomic status. Cox proportional hazard regression analysis was used to evaluate the association between osteoporosis and AMD. The main outcome measure is the occurrence of newly diagnosed AMD.<br><br>RESULTS: The hazard ratio (HR) of AMD in the osteoporosis group was 1.34 times higher than in the comparison group (95% confidence interval [CI] 1.22-1.47, p < 0.05). The AMD-free survival rate of the osteoporosis group was significantly lower than that of the comparison group (p < 0.0001). Sex-stratified analysis revealed a significantly increased risk of AMD in both osteoporotic men (HR 1.45; 95% CI 1.20-1.76, p = 0.0002) and women (HR 1.31; 95% CI 1.17-1.46, p < 0.0001) compared with their non-osteoporotic counterparts.<br><br>CONCLUSION: This longitudinal follow-up study revealed an increased risk of developing AMD in both men and women with osteoporosis.},
}
@article {pmid36826042,
year = {2023},
author = {Strzalka-Mrozik, B and Madej, M and Kurowska, N and Kruszniewska-Rajs, C and Kimsa-Dudek, M and Adamska, J and Gola, JM},
title = {Changes in the Expression Profile of Pyroptosis-Related Genes in Senescent Retinal Pigment Epithelial Cells after Lutein Treatment.},
journal = {Current issues in molecular biology},
volume = {45},
number = {2},
pages = {1500-1518},
pmid = {36826042},
issn = {1467-3045},
support = {PCN-1-036/N/1/F//Medical University of Silesia/ ; },
abstract = {Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which is constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used to prevent this process in humans, including lutein. This study aims to determine the differences in the expression patterns of pyroptosis genes in senescent human retinal pigment epithelial cell line ARPE-19 exposed to lutein. Changes in the expression of pyroptosis-related genes were assessed by oligonucleotide microarrays, and the results were validated by real-time RT-qPCR. The microarray analysis showed seven transcripts were differentially expressed both in the H2O2-treated cells versus the controls and in the lutein/H2O2-treated cells compared to the H2O2-treated cells (FC > 2.0). Depending on the used lutein, H2O2, or co-treatment of ARPE-19 cells, statistically significant differences in the expression of TXNIP, CXCL8, BAX, and CASP1 genes were confirmed by the RT-qPCR (p < 0.05). A STRING database analysis showed that the proteins encoded by the analyzed genes form a strong interaction network (p < 0.001). These data indicate that lutein modulates the expression level of pyroptosis-related genes, which may be useful for the development of new methods preventing pyroptosis pathway activation in the future.},
}
@article {pmid36824443,
year = {2023},
author = {Chen, Q and Lin, H and Li, S and Deng, X and Zhang, J},
title = {Mini-αA Upregulates the miR-155-5p Target Gene CDK2 and Plays an Antiapoptotic Role in Retinal Pigment Epithelial Cells during Oxidative Stress.},
journal = {Journal of ophthalmology},
volume = {2023},
number = {},
pages = {6713094},
pmid = {36824443},
issn = {2090-004X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of serious vision loss in the elderly. Regulating microRNA (miRNA) gene expression offers exciting new avenues for treating AMD. This study aimed to investigate whether miRNAs and their target genes play an antiapoptotic role during oxidative stress-induced apoptosis of retinal pigment epithelial (RPE) cells via mini-αA.<br><br>METHODS: ARPE-19&#x2009;cells were treated with 3.5&#x2009;mM NaIO3 for 48&#x2009;h to establish a retinal degeneration model. Cells were treated with mini-&#x3b1;A (10, 15, and 20&#x2009;&#x3bc;M) for 4&#x2009;h. miR-155-5p was knocked down and overexpressed. Cell viability and apoptosis were measured using the Cell Counting Kit-8 assay and flow cytometry, respectively. The reactive oxygen species level was detected by flow cytometry. miR-155-5p target genes were predicted via bioinformatics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for miR-155-5p target genes. A quantitative real-time polymerase chain reaction was performed to detect miRNAs and cell cycle-related target genes. Western blotting was performed to measure the levels of apoptotic pathway genes encoding Bcl-2, Bax, cleaved caspase-3, and cyclin-dependent kinase 2 (CDK2). Dual-luciferase reporter gene assay was performed to verify the targeted binding relationship between miR-155-5p and CDK2.<br><br>RESULTS: NaIO3 can induce oxidative damage and promote apoptosis. Conversely, mini-&#x3b1;A had inhibitory effects and could reverse the oxidative damage and apoptosis triggered by NaIO3 in the retinal degeneration model. The expression of miR-155-5p was upregulated in cells treated with NaIO3 and was downregulated after mini-&#x3b1;A treatment. Furthermore, miR-155-5p can target the following cell cycle-related and proliferation-related genes: CDK2, CDK4, CCND1, and CCND2. Moreover, our study indicated that miR-155-5p was involved in the antioxidative damage and antiapoptotic effects of mini-&#x3b1;A via CDK2 regulation.<br><br>CONCLUSIONS: miR-155-5p promotes the antioxidative damage and antiapoptotic effects of mini-&#x3b1;A during oxidative stress-induced apoptosis of RPE cells via CDK2 regulation. This study provides a new therapeutic target for AMD.},
}
@article {pmid36823538,
year = {2023},
author = {Yi, C and Liu, J and Deng, W and Luo, C and Qi, J and Chen, M and Xu, H},
title = {Old age promotes retinal fibrosis in choroidal neovascularization through circulating fibrocytes and profibrotic macrophages.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
pages = {45},
pmid = {36823538},
issn = {1742-2094},
support = {MR/W004682/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Mice ; Animals ; Mice, Inbred C57BL ; Fibrosis ; *Choroidal Neovascularization/metabolism ; Cytokines/metabolism ; Collagen/metabolism ; Macrophages/metabolism ; },
abstract = {BACKGROUND: Retinal fibrosis affects 40-70% of neovascular age-related macular degeneration patients. This study investigated the effect of ageing on subretinal fibrosis secondary to choroidal neovascularization and the mechanism of action.<br><br>METHODS: Subretinal fibrosis was induced in young (2.5-month) and aged (15-16-month) C57BL/6J mice using the two-stage laser protocol. Five and 30&#xa0;days later, eyes were collected and stained for CD45 and collagen-1 and observed by confocal microscopy. Fibrocytes (CD45[+]collagen-1[+]) were detected in the bone marrow (BM), blood and fibrotic lesions by flow cytometry and confocal microscopy, respectively. BM-derived macrophages (BMDMs) were cultured from young and aged mice with or without TGF-&#x3b2;1 (10&#xa0;ng/mL) treatment. The expression of mesenchymal marker &#x3b1;SMA (Acta2), fibronectin (Fn1) and collagen-1 (Col1a1) was examined by qPCR and immunocytochemistry, whereas cytokine/chemokine production was measured using the Luminex multiplex cytokine assay. BM were transplanted from 22-month (Ly5.2) aged mice into 2.5-month (Ly5.1) young mice and vice versa. Six weeks later, subretinal fibrosis was induced in recipient mice and eyes were collected for evaluation of fibrotic lesion size.<br><br>RESULTS: Under normal conditions, the number of circulating fibrocytes (CD45[+]collagen-1[+]) and the expression levels of Tgfb1, Col1a1, Acta2 and Fn1 in BMDMs were significantly higher in aged mice compared to young mice. Induction of subretinal fibrosis significantly increased the number of circulating fibrocytes, enhanced the expression of Col1a1, Acta2 and Fn1 and the production of soluble urokinase plasminogen activator surface receptor (suPAR) but decreased the production of CXCL10 in BMDMs. BMDMs from aged subretinal fibrosis mice produced significantly higher levels of VEGF, angiopoietin-2 and osteopontin than cells from young subretinal fibrosis mice. The subretinal fibrotic lesion in 15-16-month aged mice was 62% larger than that in 2.5-month young mice. The lesion in aged mice contained a significantly higher number of fibrocytes compared to that in young mice. The number of circulating fibrocytes positively correlated with the size of&#xa0;subretinal fibrotic lesion. Transplantation of BM from aged mice significantly increased subretinal fibrosis in young mice.<br><br>CONCLUSIONS: A retina-BM-blood-retina pathway of fibrocyte/macrophage recruitment exists during retinal injury. Ageing promotes subretinal fibrosis through higher numbers of circulating fibrocytes and profibrotic potential of BM-derived macrophages.},
}
@article {pmid36823223,
year = {2023},
author = {Zehden, JA and Ghosh, A and Soundararajan, S and Tsujimoto, THM and Jiang, H and Lin, FC and Blahnik, T and Fleischman, D and Zhang, AY},
title = {The effect of a brief, unplanned treatment delay on neovascular age-related macular degeneration patients: a retrospective cohort study.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {3156},
pmid = {36823223},
issn = {2045-2322},
mesh = {Humans ; Ranibizumab ; Angiogenesis Inhibitors ; Retrospective Studies ; Vascular Endothelial Growth Factor A ; Time-to-Treatment ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy ; },
abstract = {Non-compliance to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy can result in increased disease activity in neovascular age-related macular degeneration (nAMD). Our study aims to determine effects of unplanned delay in anti-VEGF injection treatment for nAMD. This retrospective observational study included patients with delays in receiving intravitreal injections for nAMD treatment from March to May 2020 by at least 21 days. Baseline demographic and clinical characteristics, visual acuity (VA), central macular thickness (CMT) measured on optical coherence tomography (OCT), and duration of delayed treatment were analyzed for 3 time points, the pre-delay visit (v1) and post-delay visits (v2 and v3). Data were compared to age-matched controls treated for nAMD in 2019 without delay. Demographic characteristics were compared using two-sample t-tests for continuous variables and Pearson's chi-square tests for categorical variables. For the two primary outcomes of interest, VA and CMT, means and standard deviations were reported for each combination of group and time. Each outcome was modeled using a linear mixed model with the group, time and group-time interaction as fixed effects. A total of 69 patients (99 eyes) in the treatment delay group and 44 patients (69 eyes) in the control group were identified. Statistically significant differences between control and delayed groups were detected for VA (difference in mean logMAR = 0.16; 95% CI 0.06, 0.27; p = 0.002) and CMT (difference in mean CMT = 29; 95% CI 12, 47; p = 0.001) at v2. No differences were detected for v1 and v3 time points for both outcomes. An unplanned delay in intravitreal injection treatment for nAMD resulted in an increase in CMT and worsening of VA compared to controls observed at v2. At v3, CMT and VA recovered to near v1 levels. This study demonstrates that a one-time, brief interruption in treatment for nAMD results in reversible, temporary worsening.},
}
@article {pmid36822488,
year = {2023},
author = {Lin, Z and Zhou, L and Huang, C and Li, Z and Lu, T and Cong, Q and Liang, J and Zhong, X and Lu, L and Jin, C},
title = {Twenty-year outcome in neovascular age-related macular degeneration treated with photodynamic therapy and intravitreal bevacizumab/ranibizumab injections: A case report.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {42},
number = {},
pages = {103349},
doi = {10.1016/j.pdpdt.2023.103349},
pmid = {36822488},
issn = {1873-1597},
mesh = {Female ; Humans ; Middle Aged ; Ranibizumab ; Bevacizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Cicatrix/drug therapy ; Treatment Outcome ; Photosensitizing Agents/therapeutic use ; *Photochemotherapy/methods ; *Macular Degeneration/drug therapy ; Atrophy/drug therapy ; Intravitreal Injections ; Tomography, Optical Coherence ; },
abstract = {A 64-year-old female presented with acute painless vision loss in the left eye was diagnosed with neovascular age-related macular degeneration. During the 20-year follow-up, the patient experienced subretinal fluid, subretinal hemorrhage, pigmentary epithelium detachment, intraretinal fluid, subretinal scar formation and macular atrophy. A total of 3 PDT treatments, 3 intravitreal bevacizumab and 16 ranibizumab injections were performed in the left eye. At the last visit, she remained best-corrected visual acuity of 20/200 with foveal macular atrophy and subfoveal fibrotic scar.},
}
@article {pmid36818570,
year = {2023},
author = {Su, N and Hansen, U and Plagemann, T and Gäher, K and Leclaire, MD and König, J and Höhn, A and Grune, T and Uhlig, CE and Eter, N and Heiduschka, P},
title = {Sub-Retinal Injection of Human Lipofuscin in the Mouse - A Model of "Dry" Age-Related Macular Degeneration?.},
journal = {Aging and disease},
volume = {14},
number = {1},
pages = {184-203},
pmid = {36818570},
issn = {2152-5250},
abstract = {Lipofuscin (LF) accumulates during lifetime in the retinal pigment epithelium (RPE) and is thought to play a crucial role in intermediate and late age-related macular degeneration (AMD). In an attemt to simulate aged retina and to study response of retinal microglia and RPE cells to LF, we injected a suspension of LF into the subretinal space of adult mice. LF suspension was obtained from human donor eyes. Subretinal injection of PBS or sham injection served as a control. Eyes were inspected by autofluorescence and optical coherence tomography, by electroretinography and on histological and ultrastructural levels. Levels of cytokine mRNA were determined by quantitative PCR separately in the RPE/choroid complex and in the retina. After injection of LF, microglial cells migrated quickly into the subretinal space to close proximity to RPE cells and phagocytosed LF particles. Retinal function was affected only slightly by LF within the first two weeks. After longer time, RPE cells showed clear signs of melanin loss and degradation. Levels of mRNA of inflammatory cytokines increased sharply after injection of both PBS and LF and were higher in the RPE/choroid complex than in the retina and were slightly higher after LF injection. In conclusion, subretinal injection of LF causes an activation of microglial cells and their migration into subretinal space, enhanced expression of inflammatory cytokines and a gradual degradation of RPE cells. These features are found also in an aging retina, and subretinal injection of LF could be a model for intermediate and late AMD.},
}
@article {pmid36817116,
year = {2023},
author = {Zhu, Y and Yang, H and Han, L and Mervin, LH and Hosseini-Gerami, L and Li, P and Wright, P and Trapotsi, MA and Liu, K and Fan, TP and Bender, A},
title = {In silico prediction and biological assessment of novel angiogenesis modulators from traditional Chinese medicine.},
journal = {Frontiers in pharmacology},
volume = {14},
number = {},
pages = {1116081},
pmid = {36817116},
issn = {1663-9812},
abstract = {Uncontrolled angiogenesis is a common denominator underlying many deadly and debilitating diseases such as myocardial infarction, chronic wounds, cancer, and age-related macular degeneration. As the current range of FDA-approved angiogenesis-based medicines are far from meeting clinical demands, the vast reserve of natural products from traditional Chinese medicine (TCM) offers an alternative source for developing pro-angiogenic or anti-angiogenic modulators. Here, we investigated 100 traditional Chinese medicine-derived individual metabolites which had reported gene expression in MCF7 cell lines in the Gene Expression Omnibus (GSE85871). We extracted literature angiogenic activities for 51 individual metabolites, and subsequently analysed their predicted targets and differentially expressed genes to understand their mechanisms of action. The angiogenesis phenotype was used to generate decision trees for rationalising the poly-pharmacology of known angiogenesis modulators such as ferulic acid and curculigoside and validated by an in vitro endothelial tube formation assay and a zebrafish model of angiogenesis. Moreover, using an in silico model we prospectively examined the angiogenesis-modulating activities of the remaining 49 individual metabolites. In vitro, tetrahydropalmatine and 1 beta-hydroxyalantolactone stimulated, while cinobufotalin and isoalantolactone inhibited endothelial tube formation. In vivo, ginsenosides Rb3 and Rc, 1 beta-hydroxyalantolactone and surprisingly cinobufotalin, restored angiogenesis against PTK787-induced impairment in zebrafish. In the absence of PTK787, deoxycholic acid and ursodeoxycholic acid did not affect angiogenesis. Despite some limitations, these results suggest further refinements of in silico prediction combined with biological assessment will be a valuable platform for accelerating the research and development of natural products from traditional Chinese medicine and understanding their mechanisms of action, and also for other traditional medicines for the prevention and treatment of angiogenic diseases.},
}
@article {pmid36816211,
year = {2023},
author = {Han, Y and Yang, KH and He, DX and Yu, CF and Tao, L and Liao, CY and Cai, BX and Liu, ZG and Qiu, Y and Wu, YL},
title = {Effect of palmitoylethanolamide on degeneration of a human-derived retinal pigment epithelial cell induced by all-trans retinal.},
journal = {International journal of ophthalmology},
volume = {16},
number = {2},
pages = {191-200},
pmid = {36816211},
issn = {2222-3959},
abstract = {AIM: To study the effect of palmitoylethanolamide (PEA) on apoptosis of retinal pigment epithelial (RPE) cells induced by all-trans retinal (atRAL) and to explore the possible molecular mechanism.<br><br>METHODS: CellTiter 96[&#xae;] Aqueous One Solution Cell Proliferation Assay (MTS) was used to detect the effect of PEA on human-derived retinal epithelial cells (ARPE-19) viability induced by atRAL. A Leica DMi8 inverted microscope was used to observe cell morphology. Reactive oxygen species (ROS) production was evaluated with 2',7'-dichlorodihydrof-luorescein diacetate (H2DCFDA) staining and fluorescence microscopy. Expression of c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), c-Jun, phosphorylated c-Jun (p-c-Jun), Bak, cleaved caspase-3, C/EBP homologous protein (CHOP), and binding (Bip) protein levels were tested by Western blot. Abca4 [-/-] Rdh8 [-/-] mice, mouse models of atRAL clearance defects which displays some symbolic characteristics of dry age-related macular degeneration (AMD) and Stargardt disease (STGD1). In the animal models, PEA was injected intraperitoneally. The full-field electroretinogram was used to detect visual function under scotopic conditions traced from mice. Optical coherence tomography showed reconstitution or thickening of the retinal pigment epithelium layer. Effect of PEA on fundus injury induced by light in Abca4[-/-]Rdh8[-/-] mice was observed by fundus photography.<br><br>RESULTS: PEA ameliorated ARPE-19 cells apoptosis and inhibited ROS (including mitochondrial ROS) production induced by atRAL. PEA improved the retinal functional, prohibited both RPE and photoreceptor from death, ameliorates light-induced fundus impairment in Abca4 [-/-] Rdh8 [-/-] mice. In vitro and in vivo, PEA inhibited JNK, p-JNK, c-Jun, p-c-Jun, Bak, cleaved caspase-3, CHOP, and Bip protein levels induced by all-trans retinal in ARPE-19 cells.<br><br>CONCLUSION: PEA has effect on treating RPE cells apoptosis in retinopathy caused by atRAL accumulation. PEA is a potential treatment strategy for dry AMD and STGD1. The molecular mechanism is affecting the ROS-JNK-CHOP signaling pathway partly.},
}
@article {pmid36812925,
year = {2023},
author = {, and , and , },
title = {[Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration - Statement of the German Society of Ophthalmology (DOG), the German Retina Society (RG) and the German Professional Asscociation of Ophthalmologists (BVA). Stand 15.10.2022].},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {240},
number = {2},
pages = {180-189},
doi = {10.1055/a-1998-8890},
pmid = {36812925},
issn = {1439-3999},
mesh = {Humans ; *Ophthalmology ; *Ophthalmologists ; Retina ; Societies, Medical ; *Macular Degeneration ; Germany ; },
}
@article {pmid36812608,
year = {2023},
author = {Rudas, A and Chiang, JN and Corradetti, G and Rakocz, N and Avram, O and Halperin, E and Sadda, SR},
title = {Automated large-scale prediction of exudative AMD progression using machine-read OCT biomarkers.},
journal = {PLOS digital health},
volume = {2},
number = {2},
pages = {e0000106},
pmid = {36812608},
issn = {2767-3170},
abstract = {Age-related Macular Degeneration (AMD) is a major cause of irreversible vision loss in individuals over 55 years old in the United States. One of the late-stage manifestations of AMD, and a major cause of vision loss, is the development of exudative macular neovascularization (MNV). Optical Coherence Tomography (OCT) is the gold standard to identify fluid at different levels within the retina. The presence of fluid is considered the hallmark to define the presence of disease activity. Anti-vascular growth factor (anti-VEGF) injections can be used to treat exudative MNV. However, given the limitations of anti-VEGF treatment, as burdensome need for frequent visits and repeated injections to sustain efficacy, limited durability of the treatment, poor or no response, there is a great interest in detecting early biomarkers associated with a higher risk for AMD progression to exudative forms in order to optimize the design of early intervention clinical trials. The annotation of structural biomarkers on optical coherence tomography (OCT) B-scans is a laborious, complex and time-consuming process, and discrepancies between human graders can introduce variability into this assessment. To address this issue, a deep-learning model (SLIVER-net) was proposed, which could identify AMD biomarkers on structural OCT volumes with high precision and without human supervision. However, the validation was performed on a small dataset, and the true predictive power of these detected biomarkers in the context of a large cohort has not been evaluated. In this retrospective cohort study, we perform the largest-scale validation of these biomarkers to date. We also assess how these features combined with other EHR data (demographics, comorbidities, etc) affect and/or improve the prediction performance relative to known factors. Our hypothesis is that these biomarkers can be identified by a machine learning algorithm without human supervision, in a way that they preserve their predictive nature. The way we test this hypothesis is by building several machine learning models utilizing these machine-read biomarkers and assessing their added predictive power. We found that not only can we show that the machine-read OCT B-scan biomarkers are predictive of AMD progression, we also observe that our proposed combined OCT and EHR data-based algorithm outperforms the state-of-the-art solution in clinically relevant metrics and provides actionable information which has the potential to improve patient care. In addition, it provides a framework for automated large-scale processing of OCT volumes, making it possible to analyze vast archives without human supervision.},
}
@article {pmid36812561,
year = {2022},
author = {Lu, L and Ausayakhun, S and Ausayakuhn, S and Khunsongkiet, P and Apivatthakakul, A and Sun, CQ and Kim, TN and Lee, M and Tsui, E and Sutra, P and Keenan, JD},
title = {Diagnostic accuracy of handheld fundus photography: A comparative study of three commercially available cameras.},
journal = {PLOS digital health},
volume = {1},
number = {11},
pages = {e0000131},
pmid = {36812561},
issn = {2767-3170},
abstract = {The objective of this study was to compare the sensitivity and specificity of handheld fundus cameras in detecting diabetic retinopathy (DR), diabetic macular edema (DME), and macular degeneration. Participants in the study, conducted at Maharaj Nakorn Hospital in Northern Thailand between September 2018 and May 2019, underwent an ophthalmologist examination as well as mydriatic fundus photography with three handheld fundus cameras (iNview, Peek Retina, Pictor Plus). Photographs were graded and adjudicated by masked ophthalmologists. Outcome measures included the sensitivity and specificity of each fundus camera for detecting DR, DME, and macular degeneration, relative to ophthalmologist examination. Fundus photographs of 355 eyes from 185 participants were captured with each of the three retinal cameras. Of the 355 eyes, 102 had DR, 71 had DME, and 89 had macular degeneration on ophthalmologist examination. The Pictor Plus was the most sensitive camera for each of the diseases (73-77%) and also achieved relatively high specificity (77-91%). The Peek Retina was the most specific (96-99%), although in part due to its low sensitivity (6-18%). The iNview had slightly lower estimates of sensitivity (55-72%) and specificity (86-90%) compared to the Pictor Plus. These findings demonstrated that the handheld cameras achieved high specificity but variable sensitivities in detecting DR, DME, and macular degeneration. The Pictor Plus, iNview, and Peek Retina would have distinct advantages and disadvantages when applied for utilization in tele-ophthalmology retinal screening programs.},
}
@article {pmid36810060,
year = {2023},
author = {Khachigian, LM and Liew, G and Teo, KYC and Wong, TY and Mitchell, P},
title = {Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration.},
journal = {Journal of translational medicine},
volume = {21},
number = {1},
pages = {133},
pmid = {36810060},
issn = {1479-5876},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Macular Degeneration ; Ranibizumab/therapeutic use ; Bevacizumab/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Intravitreal Injections ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.},
}
@article {pmid36808601,
year = {2023},
author = {Cougnard-Gregoire, A and Merle, BMJ and Aslam, T and Seddon, JM and Aknin, I and Klaver, CCW and Garhöfer, G and Layana, AG and Minnella, AM and Silva, R and Delcourt, C},
title = {Blue Light Exposure: Ocular Hazards and Prevention-A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {2},
pages = {755-788},
pmid = {36808601},
issn = {2193-8245},
abstract = {INTRODUCTION: Exposure to blue light has seriously increased in our environment since the arrival of light emitting diodes (LEDs) and, in recent years, the proliferation of digital devices rich in blue light. This raises some questions about its potential deleterious effects on eye health. The aim of this narrative review is to provide an update on the ocular effects of blue light and to discuss the efficiency of methods of protection and prevention against potential blue light-induced ocular injury.<br><br>METHODS: The search of relevant English articles was conducted in PubMed, Medline, and Google Scholar databases until December 2022.<br><br>RESULTS: Blue light exposure provokes photochemical reactions in most eye tissues, in particular the cornea, the lens, and the retina. In vitro and in vivo studies have shown that certain exposures to blue light (depending on the wavelength or intensity) can cause temporary or permanent damage to some structures of the eye, especially the retina. However, currently, there is no evidence that screen use and LEDs in normal use are deleterious to the human retina. Regarding protection, there is currently no evidence of a beneficial effect of blue blocking lenses for the prevention of eye diseases, in particular age-related macular degeneration (AMD). In humans, macular pigments (composed of lutein and zeaxanthin) represent a natural protection by filtering blue light, and can be increased through increased intake from foods or food supplements. These nutrients are associated with lower risk for AMD and cataract. Antioxidants such as vitamins C, E, or zinc might also contribute to the prevention of photochemical ocular damage by preventing oxidative stress.<br><br>CONCLUSION: Currently, there is no evidence that LEDs in normal use at domestic intensity levels or in screen devices are retinotoxic to the human eye. However, the potential toxicity of long-term cumulative exposure and the dose-response effect are currently unknown.},
}
@article {pmid36804905,
year = {2023},
author = {Fitch, TC and Frank, SI and Li, YK and Saint-Geniez, M and Kim, LA and Shu, DY},
title = {Real-Time Analysis of Bioenergetics in Primary Human Retinal Pigment Epithelial Cells Using High-Resolution Respirometry.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {192},
pages = {},
doi = {10.3791/64572},
pmid = {36804905},
issn = {1940-087X},
support = {R01 EY027739/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Kinetics ; *Energy Metabolism ; *Glycolysis ; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/metabolism/pharmacology ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Metabolic dysfunction of retinal pigment epithelial cells (RPE) is a key pathogenic driver of retinal diseases such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Since RPE are highly metabolically-active cells, alterations in their metabolic status reflect changes in their health and function. High-resolution respirometry allows for real-time kinetic analysis of the two major bioenergetic pathways, glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), through quantification of the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), respectively. The following is an optimized protocol for conducting high-resolution respirometry on primary human retinal pigment epithelial cells (H-RPE). This protocol provides a detailed description of the steps involved in producing bioenergetic profiles of RPE to define their basal and maximal OXPHOS and glycolytic capacities. Exposing H-RPE to different drug injections targeting the mitochondrial and glycolytic machinery results in defined bioenergetic profiles, from which key metabolic parameters can be calculated. This protocol highlights the enhanced response of BAM15 as an uncoupling agent compared to carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) to induce the maximal respiration capacity in RPE. This protocol can be utilized to study the bioenergetic status of RPE under different disease conditions and test the efficacy of novel drugs in restoring the basal metabolic status of RPE.},
}
@article {pmid36803995,
year = {2023},
author = {Zandi, S and Li, Y and Jahnke, L and Schweri-Olac, A and Ishikawa, K and Wada, I and Nakao, S and Zinkernagel, MS and Enzmann, V},
title = {Animal model of subretinal fibrosis without active choroidal neovascularization.},
journal = {Experimental eye research},
volume = {229},
number = {},
pages = {109428},
doi = {10.1016/j.exer.2023.109428},
pmid = {36803995},
issn = {1096-0007},
mesh = {Mice ; Animals ; *Collagen Type I ; Vascular Endothelial Growth Factor A/metabolism ; *Choroidal Neovascularization/diagnosis/etiology/drug therapy ; Fluorescein Angiography ; Disease Models, Animal ; Fibrosis ; Tomography, Optical Coherence ; },
abstract = {Subretinal fibrosis can occur during neovascular age-related macular degeneration (nAMD) and consequently provokes progressing deterioration of AMD patient's vision. Intravitreal anti-vascular endothelial growth factor (VEGF) injections decrease choroidal neovascularization (CNV), however, subretinal fibrosis remains principally unaffected. So far, no successful treatment nor established animal model for subretinal fibrosis exists. In order to investigate the impact of anti-fibrotic compounds on solely fibrosis, we refined a time-dependent animal model of subretinal fibrosis without active choroidal neovascularization (CNV). To induce CNV-related fibrosis, wild-type (WT) mice underwent laser photocoagulation of the retina with rupture of Bruch's membrane. The lesions volume was assessed with optical coherence tomography (OCT). CNV (Isolectin B4) and fibrosis (type 1 collagen) were separately quantified with confocal microscopy of choroidal whole-mounts at every time point post laser induction (day 7-49). In addition, OCT, autofluorescence and fluorescence angiography were carried out at designated timepoints (day 7, 14, 21, 28, 35, 42, 49) to monitor CNV and fibrosis transformation over time. From 21 to 49 days post laser lesion leakage in the fluorescence angiography decreased. Correspondingly, Isolectin B4 decreased in lesions of choroidal flat mounts and type 1 collagen increased. Fibrosis markers, namely vimentin, fibronectin, alpha-smooth muscle actin (α-SMA) and type 1 collagen were detected at different timepoints of tissue repair in choroids and retinas post laser. These results prove that the late phase of the CNV-related fibrosis model enables screening of anti-fibrotic compounds to accelerate the therapeutic advancement for the prevention, reduction, or inhibition of subretinal fibrosis.},
}
@article {pmid36803692,
year = {2023},
author = {Xue, K and Hua, P and Maguire, MG and Daniel, E and Jaffe, GJ and Grunwald, JE and Ying, GS and , },
title = {Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {7},
pages = {564-572},
pmid = {36803692},
issn = {2468-6530},
support = {R21 EY028998/EY/NEI NIH HHS/United States ; U10 EY023530/EY/NEI NIH HHS/United States ; U10 EY017825/EY/NEI NIH HHS/United States ; U10 EY017826/EY/NEI NIH HHS/United States ; U10 EY017828/EY/NEI NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; U10 EY017823/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Ranibizumab ; Bevacizumab ; *Macular Degeneration/diagnosis/drug therapy ; },
abstract = {OBJECTIVE: To predict 2-year visual acuity (VA) responses to anti-VEGF therapy, using early morphologic and functional responses in patients with neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Cohort within a randomized clinical trial.<br><br>PARTICIPANTS: A total of 1185 participants with untreated active nAMD and best-corrected visual acuity (BCVA) 20/25 to 20/320 at baseline.<br><br>METHODS: Secondary analysis of data from participants randomized to either ranibizumab or bevacizumab and to 1 of 3 dosing regimens. Associations of 2-year BCVA responses with baseline morphologic and functional characteristics and their change from baseline at 3 months were assessed, using univariable and multivariable linear regression models for BCVA change and logistic regression models for &#x2265; 3-line BCVA gain from baseline. The performance of predictions for 2-year BCVA outcomes using these characteristics was assessed using R[2] for BCVA change and area under the receiver operating characteristic curve (AUC) for &#x2265; 3-line BCVA gain.<br><br>MAIN OUTCOME MEASURES: Best-corrected visual acuity change and &#x2265; 3-line gain from baseline at year&#xa0;2.<br><br>RESULTS: In multivariable analyses that included previously reported significant baseline predictors (baseline BCVA, baseline macular atrophy, baseline retinal pigment epithelium elevation [RPEE], and maximum width and early BCVA change from baseline at 3 months), new RPEE occurrence at 3 months was significantly associated with more BCVA gain at 2 years (10.2 letters vs. 3.5 letters for RPEE resolved, P < 0.001), and none of the other morphologic responses at 3 months were significantly associated with BCVA responses at 2 years. These significant predictors moderately predicted 2-year BCVA gain with an R[2]&#xa0;= 0.36. Baseline BCVA and &#x2265; 3-line BCVA gain at 3 months predicted 2-year &#x2265; 3-line gain with AUC 0.83 (95% confidence interval, 0.81-0.86).<br><br>CONCLUSIONS: Most structural responses on OCT at 3 months were not independently predictive of the 2-year BCVA responses, which were associated with baseline factors and the 3-month BCVA response to anti-VEGF therapy. A combination of baseline predictors, early BCVA, and morphologic responses at 3 months only moderately predicted the long-term BCVA responses. Future research is needed to better understand the factors contributing to the variation in long-term vision outcomes with anti-VEGF therapy.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36802303,
year = {2023},
author = {Shen, B and Gao, H and Zhang, D and Yu, H and Chen, J and Huang, S and Gu, P and Zhong, Y},
title = {miR-124-3p regulates the proliferation and differentiation of retinal progenitor cells through SEPT10.},
journal = {Cell and tissue research},
volume = {392},
number = {3},
pages = {689-704},
pmid = {36802303},
issn = {1432-0878},
support = {NO. 81870652//National Natural Science Foundation of China/ ; NO. 82070953//National Natural Science Foundation of China/ ; NO. 8200088//National Natural Science Foundation of China/ ; NO.82101179//National Natural Science Foundation of China/ ; NO.32000972//National Natural Science Foundation of China/ ; NO.82000885//National Natural Science Foundation of China/ ; NO.21YF1422900//Shanghai Sailing Program of China/ ; NO. 21ZR1439700//Natural Science Foundation of Shanghai/ ; },
mesh = {Humans ; Cell Proliferation/genetics ; Cells, Cultured ; Stem Cells ; Cell Differentiation/genetics ; *MicroRNAs/genetics/metabolism ; *Retinal Degeneration ; },
abstract = {Retinal degenerative diseases such as glaucoma, retinitis pigmentosa, and age-related macular degeneration pose serious threats to human visual health due to lack of effective therapeutic approaches. In recent years, the transplantation of retinal progenitor cells (RPCs) has shown increasing promise in the treatment of these diseases; however, the application of RPC transplantation is limited by both their poor proliferation and their differentiation capabilities. Previous studies have shown that microRNAs (miRNA) act as essential mediators in the fate determination of stem/progenitor cells. In this study, we hypothesized that miR-124-3p plays a regulatory role in the fate of RPC determination by targeting Septin10 (SEPT10) in vitro. We observed that the overexpression of miR124-3p downregulates SEPT10 expression in RPCs, leading to reduced RPC proliferation and increased differentiation, specifically towards both neurons and ganglion cells. Conversely, antisense knockdown of miR-124-3p was shown to boost SEPT10 expression, enhance RPC proliferation, and attenuate differentiation. Moreover, overexpression of SEPT10 rescued miR-124-3p-caused proliferation deficiency while weakening the enhancement of miR-124-3p-induced-RPC differentiation. Results from this study show that miR-124-3p regulates RPC proliferation and differentiation by targeting SEPT10. Furthermore, our findings enable a more comprehensive understanding into the mechanisms of proliferation and differentiation of RPC fate determination. Ultimately, this study may be useful for helping researchers and clinicians to develop more promising and effective approaches to optimize the use of RPCs in treating retinal degeneration diseases.},
}
@article {pmid36801797,
year = {2023},
author = {Piskova, T and Kozyrina, AN and Di Russo, J},
title = {Mechanobiological implications of age-related remodelling in the outer retina.},
journal = {Biomaterials advances},
volume = {147},
number = {},
pages = {213343},
doi = {10.1016/j.bioadv.2023.213343},
pmid = {36801797},
issn = {2772-9508},
mesh = {Humans ; Aged ; *Pigment Epithelium of Eye/metabolism/pathology ; Retina/metabolism/pathology ; Choroid/metabolism/pathology ; Bruch Membrane/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; },
abstract = {The outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the extracellular matrix compartment named Bruch's membrane, situated between the retinal epithelium and the choroid. Like many tissues, the retina experiences age-related structural and metabolic changes, which are relevant for understanding major blinding diseases of the elderly, such as age-related macular degeneration. Compared with other tissues, the retina mainly comprises postmitotic cells, making it less able to maintain its mechanical homeostasis over the years functionally. Aspects of retinal ageing, like the structural and morphometric changes of the pigment epithelium and the heterogenous remodelling of the Bruch's membrane, imply changes in tissue mechanics and may affect functional integrity. In recent years, findings in the field of mechanobiology and bioengineering highlighted the importance of mechanical changes in tissues for understanding physiological and pathological processes. Here, we review the current knowledge of age-related changes in the outer retina from a mechanobiological perspective, aiming to generate food for thought for future mechanobiology studies in the outer retina.},
}
@article {pmid36800952,
year = {2023},
author = {Wang, Y and Shen, H and Pang, L and Qiu, B and Yuan, Y and Guan, X and Xiang, X},
title = {Qihuang Granule protects the retinal pigment epithelium from oxidative stress via regulation of the alternative complement pathway.},
journal = {BMC complementary medicine and therapies},
volume = {23},
number = {1},
pages = {55},
pmid = {36800952},
issn = {2662-7671},
support = {81503618//National Natural Science Foundation of China/ ; 81670874//National Natural Science Foundation of China/ ; YN2018M703//Special Research Project in Guangdong Provincial Hospital of Chinese Medicine/ ; },
mesh = {Animals ; Mice ; *Retinal Pigment Epithelium/metabolism/pathology ; Complement Pathway, Alternative ; Hydrogen Peroxide/pharmacology ; Mice, Inbred C57BL ; Oxidative Stress ; *Macular Degeneration/drug therapy/metabolism/pathology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in elderly people, and dry AMD is the most common type of AMD. Oxidative stress and alternative complement pathway activation may play essential roles in the pathogenesis of dry AMD. There are no available drugs for dry AMD. Qihuang Granule (QHG) is an herbal formula for the treatment of dry AMD, and it achieves a good clinical effect in our hospital. However, its potential mechanism is unclear. Our study investigated the effects of QHG on oxidative stress-associated retinal damage to reveal its underlying mechanism.<br><br>METHODS: Oxidative stress models were established using H2O2 and NaIO3 in ARPE-19 cells and C57BL/6 mice. Cell apoptosis and viability were assessed using phase contrast microscopy and flow cytometry, respectively. Alterations in the mouse retinal structure were evaluated using Masson staining and transmission electron microscopy (TEM). The expression of complement factor H (CFH), complement component 3a (C3a) and complement component 5a (C5a) in retinal pigment epithelium (RPE) cells and mice was measured using RT&#x2012;PCR, Western blot analysis and ELISA.<br><br>RESULTS: Pretreatment with QHG significantly prevented cell apoptosis and disorder of the RPE and&#xa0;inner segment/outer segment (IS/OS) in H2O2-treated RPE cells and NaIO3-injected mice. QHG alleviated mitochondrial damage in mouse RPE cells, as shown by TEM. QHG also promoted CFH expression and inhibited the expression of C3a and C5a.<br><br>CONCLUSIONS: The results suggest that QHG protects the retinal pigment epithelium from oxidative stress, likely by regulating the alternative complement pathway.},
}
@article {pmid36795578,
year = {2023},
author = {Nguyen, T and Urrutia-Cabrera, D and Wang, L and Lees, JG and Wang, JH and Hung, SSC and Hewitt, AW and Edwards, TL and McLenachan, S and Chen, FK and Lim, SY and Luu, CD and Guymer, R and Wong, RCB},
title = {Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells.},
journal = {Aging},
volume = {15},
number = {6},
pages = {1713-1733},
pmid = {36795578},
issn = {1945-4589},
mesh = {Humans ; *Superoxides/metabolism ; *Macular Degeneration/genetics/pathology ; Oxidative Stress/genetics ; Retinal Pigment Epithelium/pathology ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; Nuclear Proteins/metabolism ; },
abstract = {Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. Here we report the generation of a stable human RPE cell line ARPE-19 with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. We conducted functional studies on the POLDIP2 knockout cell line and showed that it retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells. Our results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. We showed that loss of POLDIP2 caused a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2 in ARPE-19, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology.},
}
@article {pmid36795517,
year = {2023},
author = {Cayzac, V and Sagnard, M and Valero, B and Voisin, H and El Chehab, H},
title = {Retinal Pigment Epithelium Tear After Nonpenetrating Deep Sclerectomy.},
journal = {Journal of glaucoma},
volume = {32},
number = {6},
pages = {e60-e62},
doi = {10.1097/IJG.0000000000002175},
pmid = {36795517},
issn = {1536-481X},
mesh = {Male ; Humans ; Middle Aged ; Retinal Pigment Epithelium ; Angiogenesis Inhibitors/adverse effects ; Vascular Endothelial Growth Factor A ; *Retinal Perforations/diagnosis/etiology/surgery ; Intraocular Pressure ; Intravitreal Injections ; *Lacerations ; Fluorescein Angiography ; Tomography, Optical Coherence ; },
abstract = {Retinal pigment epithelium (RPE) tear is a common complication in the context of neovascular age-related macular degeneration treated by intravitreal injections of antivascular endothelial growth factor drugs. There are some reports of such complications after trabeculectomy but none after nonpenetrating deep sclerectomy (NPDS). A 57-year-old man presented to our hospital with uncontrolled advanced glaucoma of his left eye. NPDS with adjunctive use of mitomycin C was performed with no intraoperative complication. On the seventh postoperative day clinical examination and multimodal imaging revealed a macular RPE tear in the operated eye. Subretinal fluid induced by the tear resolved within 2 months with an increase in intraocular pressure. To the best of our knowledge, this article discusses the first reported case of RPE tear occurring just after NPDS.},
}
@article {pmid36795396,
year = {2023},
author = {Bjerager, J and Schneider, M and Potapenko, I and van Dijk, EHC and Faber, C and Grauslund, J and Pfau, K and Huemer, J and Muttuvelu, DV and Rasmussen, MLR and Sabaner, MC and Subhi, Y},
title = {Diagnostic Accuracy of the Amsler Grid Test for Detecting Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.},
journal = {JAMA ophthalmology},
volume = {141},
number = {4},
pages = {315-323},
pmid = {36795396},
issn = {2168-6173},
mesh = {Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/diagnosis ; Visual Field Tests/methods ; Sensitivity and Specificity ; *Geographic Atrophy ; },
abstract = {IMPORTANCE: Patients with nonneovascular age-related macular degeneration (AMD) are encouraged to use the Amsler grid test for self-assessment to facilitate early diagnosis. The test is widely recommended, suggesting a belief that it signals worsening AMD, warranting its use in home monitoring.<br><br>OBJECTIVE: To systematically review studies of the diagnostic test accuracy of the Amsler grid in the diagnosis of neovascular AMD and to perform diagnostic test accuracy meta-analyses.<br><br>DATA SOURCES: A systematic literature search was conducted in 12 databases for relevant titles from database inception until May 7, 2022.<br><br>STUDY SELECTION: Studies included those with groups defined as having (1) neovascular AMD and (2) either healthy eyes or eyes with nonneovascular AMD. The index test was the Amsler grid. The reference standard was ophthalmic examination. After removal of obviously irrelevant reports, 2 authors (J.B. and M.S.) independently screened the remaining references in full text for potential eligibility. Disagreements were resolved by a third author (Y.S.).<br><br>DATA EXTRACTION AND SYNTHESIS: Two authors (J.B. and I.P.) independently extracted all data and evaluated quality and applicability of eligible studies using the Quality Assessment of Diagnostic Accuracy Studies 2. Disagreements were resolved by a third author (Y.S.).<br><br>MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of the Amsler grid for detecting neovascular AMD with comparators being either healthy control participants or patients with nonneovascular AMD.<br><br>RESULTS: Of 523 records screened, 10 studies were included with a total of 1890 eyes (mean participant age ranging from 62 to 83 years). Sensitivity and specificity to diagnose neovascular AMD were 67% (95% CI, 51%-79%) and 99% (95% CI, 85%-100%), respectively, when comparators were healthy control participants and 71% (95% CI, 60%-80%) and 63% (95% CI, 49%-51%), respectively, when control participants were patients with nonneovascular AMD. Overall, potential sources of bias were low across studies.<br><br>CONCLUSIONS AND RELEVANCE: Although the Amsler grid is easy and inexpensive to use for detection of metamorphopsia, its sensitivity may be at levels typically not recommended for monitoring. Coupling this lower sensitivity with only moderate specificity to identify neovascular AMD in a population at risk, these findings suggest that such patients typically should be encouraged to undergo ophthalmic examination regularly, regardless of any results of Amsler grid self-assessment.},
}
@article {pmid36795164,
year = {2023},
author = {Riemer, T and Berndt, D and Böker, A and Lehmann, J and Schrifl, U and Rau, S and Rübsam, A and Joussen, AM and Zeitz, O},
title = {Correction to: Treatment of neovascular age-related macular degeneration: insights into drug-switch real-world from the Berlin Macular Registry.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {6},
pages = {1769},
doi = {10.1007/s00417-023-06011-6},
pmid = {36795164},
issn = {1435-702X},
}
@article {pmid36794741,
year = {2022},
author = {Wang, R and McClard, CK and Laswell, S and Mahmoudzadeh, R and Salabati, M and Ammar, M and Vannavong, J and Aziz, AA and Ewald, A and Calvanese, AV and Lehman, EB and Fried, S and Windham, V and Strutt, A and Saroj, N and Khanani, AM and Eichenbaum, DA and Regillo, C and Wykoff, CC},
title = {Quantifying burden of intravitreal injections: questionnaire assessment of life impact of treatment by intravitreal injections (QUALITII).},
journal = {BMJ open ophthalmology},
volume = {7},
number = {1},
pages = {},
pmid = {36794741},
issn = {2397-3269},
mesh = {Humans ; Female ; Aged ; Male ; *Diabetic Retinopathy/drug therapy ; *Macular Edema/drug therapy ; Intravitreal Injections ; *Retinal Diseases/drug therapy ; *Macular Degeneration/drug therapy ; },
abstract = {AIM: To quantify the areas of burden experienced by patients requiring repeated intravitreal injections (IVI) in the management of exudative retinal diseases.<br><br>METHODS: The validated Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections survey was administered to patients at four retina clinical practices across four US states. The primary outcome measure was Treatment Burden Score (TBS), a single score assessing overall burden.<br><br>RESULTS: Of 1416 (n=657 age-related macular degeneration; n=360 diabetic macular oedema/diabetic retinopathy; n=221 retinal vein occlusion; n=178 other/uncertain) patients, 55% were women with an average age of 70 years. Patients most frequently reported receiving IVI every 4-5 weeks (40%). The mean TBS was 16.1&#xb1;9.2 (range 1-48; scale of 1-54), and the TBS was higher in patients with diabetic macular oedema and/or diabetic retinopathy (DMO/DR) (17.1) compared with those with age-related macular degeneration (15.5) or retinal venous occlusive (15.3) (p=0.028). Though the mean level of discomfort was quite low (1.86) (scale 0-6), 50% of patients reported experiencing side effects more than half of the visits. Patients having received fewer than 5 IVI reported higher mean anxiety levels before (p=0.026), during (p=0.050) and after (p=0.016) treatment compared with patients having received more than 50 IVI. After the procedure, 42% of patients reported restrictions from usual activities due to discomfort. Patients reported a high mean satisfaction rating of 5.46 (scale 0-6) with the care of their diseases.<br><br>CONCLUSIONS: The mean TBS was moderate and highest among patients with DMO/DR. Patients with more total injections reported lower levels of discomfort and anxiety but higher disruption to daily life. Despite the challenges related to IVI, the overall satisfaction with treatment remained high.},
}
@article {pmid36794374,
year = {2024},
author = {Phakey, S and Hall, AJ and Lim, LL},
title = {Intravitreal Injection Rates for Neovascular Age-Related Macular Degeneration in Australia During the 2020 COVID-19 Lockdowns.},
journal = {Ophthalmic epidemiology},
volume = {31},
number = {1},
pages = {94-97},
doi = {10.1080/09286586.2023.2178661},
pmid = {36794374},
issn = {1744-5086},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A/therapeutic use ; Retrospective Studies ; Intravitreal Injections ; Australia/epidemiology ; *COVID-19/epidemiology ; Communicable Disease Control ; Ranibizumab/therapeutic use ; *Macular Degeneration/drug therapy/epidemiology ; *Wet Macular Degeneration/drug therapy/epidemiology ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {PURPOSE: We investigate the impact of COVID-19 and lockdowns on anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (AMD) in Victoria (Australian state with highest burden of COVID-19 in 2020) and Australia, by examining anti-VEGF prescriptions supplied for AMD treatment between 2018 and 2020.<br><br>METHODS: We performed a retrospective, population-based analysis of aflibercept and ranibizumab prescriptions supplied for the treatment of AMD in Victoria and Australia between 1 January 2018 and 31 December 2020, as recorded by the Pharmaceutical Benefits Scheme (PBS) and Repatriation PBS, the Australian Government program subsidising medication costs for Australian residents and veterans. Poisson models and univariate regression were used to descriptively examine trends in monthly anti-VEGF prescription rates with time and changes in monthly prescription rates (prescription rate ratios [RR]).<br><br>RESULTS: In 2020, anti-VEGF AMD prescription rates in Victoria decreased by 18% during the nationwide lockdown between March and May (RR 0.82, 95% CI: 0.80-0.85, p <&#xa0;.001), and by 24% during the Victorian-specific lockdown between July and October (RR 0.76, 95% CI: 0.73-0.78, p <&#xa0;.001). In Australia, prescription rates tended to decrease between January and October 2020, reducing by 25% (RR 0.75, 95% CI: 0.74-0.77, p <&#xa0;.001) between these months, including between March and April (RR 0.94, 95% CI: 0.92-0.95, p <&#xa0;.001) but not April and May (RR 1.10, 95% CI: 1.09-1.12, p <&#xa0;.001).<br><br>CONCLUSION: In 2020, anti-VEGF prescriptions for AMD treatment decreased modestly in Victoria during both lockdowns and in Australia during the year. Decreases may represent reduced treatment because of COVID-19, including public health orders, patients' self-limiting care, and ophthalmologists treating-and-extending to maximum intervals.},
}
@article {pmid36793950,
year = {2023},
author = {Panda-Jonas, S and Auffarth, GU and Jonas, JB and Jonas, RA},
title = {Myopic macular Bruch's membrane defects.},
journal = {Heliyon},
volume = {9},
number = {2},
pages = {e13257},
pmid = {36793950},
issn = {2405-8440},
abstract = {PURPOSE: To examine histologic characteristics of macular Bruchś membrane defects (BMD) in axially elongated eyes.<br><br>DESIGN: Histomorphometric study.<br><br>METHODS: Using light microscopy, we examined enucleated human globes for BMDs.<br><br>RESULTS: In 247 eyes, BMDs were detected in 15 (6.1%) eyes (axial length:27.0-36.0&#xa0;mm), in 10 of them in the macular region. Prevalence and size of BMDs (mean:1.93&#xa0;&#xb1;&#xa0;1.62&#xa0;mm; range:0.22mm-6.24&#xa0;mm) correlated with longer axial length (OR:1.52; 95%CI:1.19,1.94; P&#xa0;=&#xa0;0.001) and higher prevalence of scleral staphylomas (OR:16.3; 95%CI:2.67,99.3; P&#xa0;<&#xa0;0.001). The BMDs were smaller than corresponding gaps in the retinal pigment epithelium (RPE) (1.93&#xa0;&#xb1;&#xa0;1.62&#xa0;mm versus 2.61&#xa0;mm&#xa0;&#xb1;&#xa0;1.73&#xa0;mm; P&#xa0;=&#xa0;0.003), and larger than corresponding gaps in the inner nuclear layer (0.43&#xa0;&#xb1;&#xa0;0.76&#xa0;mm; P&#xa0;=&#xa0;0.008) and inner limiting membrane bridges (0.13&#xa0;&#xb1;&#xa0;0.33&#xa0;mm; P&#xa0;=&#xa0;0.001). Choriocapillaris thickness, BM thickness and RPE cell density did not vary (all P&#xa0;>&#xa0;0.05) between the BDM border and adjacent areas. In the BMD, choriocapillaris and RPE were absent. The sclera was thinner in the BDM area than in adjacent areas (0.28&#xa0;&#xb1;&#xa0;0.19&#xa0;mm versus 0.36&#xa0;&#xb1;&#xa0;0.13&#xa0;mm; P&#xa0;=&#xa0;0.006).<br><br>CONCLUSIONS: BMDs as hallmarks of myopic macular degeneration are characterized by longer gaps in the RPE and smaller gaps in the outer nuclear layer and inner nuclear layer, by localized scleral thinning, and by a spatial association with scleral staphylomas. Thickness of the choriocapillaris and density of the RPE cell layer, both absent within the BDMs, do not vary between the BMD border and adjacent regions. The results suggest an association between BDMs and absolute scotomas, stretching of the adjacent retinal nerve fiver layer, and an axial elongation-associated stretching effect on BM as etiology of the BDMs.},
}
@article {pmid36793623,
year = {2023},
author = {Luo, Y and Liu, J and Feng, W and Lin, D and Song, G and Chen, M and Zheng, H},
title = {Use of β‑blockers and risk of age‑related macular degeneration among hypertensive patients: An insight from The National Health and Nutrition Examination Survey.},
journal = {Medicine international},
volume = {3},
number = {1},
pages = {10},
pmid = {36793623},
issn = {2754-1304},
abstract = {Although age-related macular degeneration (AMD) is the leading cause of legal blindness, the treatment methods for AMD are limited. The aim of the present study was to examine the association between oral β-blockers (BBs) and the risk of developing AMD among hypertensive patients. For this purpose, a total of 3,311 hypertensive patients from the National Health and Nutrition Examination Survey were included in the study. The use of BBs and treatment duration data were collected using a self-reported questionnaire. AMD was diagnosed by gradable retinal images. Multivariate-adjusted survey-weighted univariate logistic regression was used to confirm the association between the use of BBs and the risk of developing AMD. The results revealed that the use of BBs exerted a beneficial effect (odds ratio (OR), 0.34; 95% confidence interval (95% CI, 0.13-0.92; P=0.04) in late-stage AMD in the multivariate adjusted model. When the BBs were classified into non-selective BBs and selective BBs, the protective effect in late-stage AMD was still observed in the non-selective BBs (OR, 0.20; 95% CI, 0.07-0.61; P<0.001). After accounting for treatment duration, long-term treatment with BBs (>6 years) was also found to reduce the risk of late-stage AMD (OR, 0.13; 95% CI, 0.03-0.63; P=0.01). In late-stage AMD, the long-term use of BBs was beneficial for geographic atrophy (OR, 0.07; 95% CI, 0.02-0.28; P<0.001). On the whole, the present study demonstrates that the use of non-selective BBs exerted a beneficial effect against the risk of late-stage AMD among hypertensive patients. Long-term treatment with BBs was also associated with lower risk of developing AMD. These findings may provide novel strategies for the management and treatment of AMD.},
}
@article {pmid36793539,
year = {2023},
author = {Gan, F and Wu, FP and Zhong, YL},
title = {Artificial intelligence method based on multi-feature fusion for automatic macular edema (ME) classification on spectral-domain optical coherence tomography (SD-OCT) images.},
journal = {Frontiers in neuroscience},
volume = {17},
number = {},
pages = {1097291},
pmid = {36793539},
issn = {1662-4548},
abstract = {PURPOSE: A common ocular manifestation, macular edema (ME) is the primary cause of visual deterioration. In this study, an artificial intelligence method based on multi-feature fusion was introduced to enable automatic ME classification on spectral-domain optical coherence tomography (SD-OCT) images, to provide a convenient method of clinical diagnosis.<br><br>METHODS: First, 1,213 two-dimensional (2D) cross-sectional OCT images of ME were collected from the Jiangxi Provincial People's Hospital between 2016 and 2021. According to OCT reports of senior ophthalmologists, there were 300 images with diabetic (DME), 303 images with age-related macular degeneration (AMD), 304 images with retinal-vein occlusion (RVO), and 306 images with central serous chorioretinopathy (CSC). Then, traditional omics features of the images were extracted based on the first-order statistics, shape, size, and texture. After extraction by the alexnet, inception_v3, resnet34, and vgg13 models and selected by dimensionality reduction using principal components analysis (PCA), the deep-learning features were fused. Next, the gradient-weighted class-activation map (Grad-CAM) was used to visualize the-deep-learning process. Finally, the fusion features set, which was fused from the traditional omics features and the deep-fusion features, was used to establish the final classification models. The performance of the final models was evaluated by accuracy, confusion matrix, and the receiver operating characteristic (ROC) curve.<br><br>RESULTS: Compared with other classification models, the performance of the support vector machine (SVM) model was best, with an accuracy of 93.8%. The area under curves AUC of micro- and macro-averages were 99%, and the AUC of the AMD, DME, RVO, and CSC groups were 100, 99, 98, and 100%, respectively.<br><br>CONCLUSION: The artificial intelligence model in this study could be used to classify DME, AME, RVO, and CSC accurately from SD-OCT images.},
}
@article {pmid36793429,
year = {2023},
author = {Abdel-Magid, AF},
title = {Plasma Kallikrein Inhibitors as Potential Treatment for Diabetic Macular Edema, Retinal Vein Occlusion, Hereditary Angioedema and Other Related Diseases.},
journal = {ACS medicinal chemistry letters},
volume = {14},
number = {2},
pages = {129-130},
pmid = {36793429},
issn = {1948-5875},
abstract = {The invention in this patent application relates to (S)-spiro[benzo[d][1,3]oxazine-4,3'-pyrrolidin]-2(1H)-one derivatives, represented generally by formula 1. These compounds are selective plasma kallikrein inhibitors and may potentially be beneficial in the treatment of several diseases and disorders, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy, and retinal vein occlusion.},
}
@article {pmid36788396,
year = {2023},
author = {Hassan, M and Rajput, SK and Salma, J and Kirmani, S and F Damji, K},
title = {The potential of stem cell therapy to tackle visual impairment.},
journal = {JPMA. The Journal of the Pakistan Medical Association},
volume = {73(Suppl 1)},
number = {2},
pages = {S79-S88},
doi = {10.47391/JPMA.AKUS-13},
pmid = {36788396},
issn = {0030-9982},
mesh = {Animals ; Quality of Life ; Vision Disorders/etiology/therapy ; *Cataract/complications ; *Glaucoma/therapy ; *Diabetic Retinopathy ; Cell- and Tissue-Based Therapy ; },
abstract = {Visual impairment adversely impacts quality of life and affects more than 295 million individuals globally. Currently, there is no cure or tissue regenerative approaches in clinical practice for vision loss caused by corneal disease, glaucoma, cataracts, macular degeneration, diabetic retinopathy, and inherited retinal disease. Stem cells-based therapeutic approaches to diseases causing moderate to severe visual impairment have shown encouraging outcomes in animal models and in vitro studies. The goal of this narrative review is to describe and evaluate the potential of stem cell-based treatment, and their advantages and safety concerns in treating conditions causing vision loss.},
}
@article {pmid36787231,
year = {2023},
author = {Hata, M and Hata, M and Andriessen, EM and Juneau, R and Pilon, F and Crespo-Garcia, S and Diaz-Marin, R and Guber, V and Binet, F and Fournier, F and Buscarlet, M and Grou, C and Calderon, V and Heckel, E and Melichar, HJ and Joyal, JS and Wilson, AM and Sapieha, P},
title = {Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life.},
journal = {The Journal of clinical investigation},
volume = {133},
number = {4},
pages = {},
pmid = {36787231},
issn = {1558-8238},
mesh = {Humans ; Microglia/pathology ; Retina/pathology ; *Choroidal Neovascularization/genetics ; *Macular Degeneration/genetics/pathology ; Inflammation/pathology ; },
abstract = {Pathological neovascularization in age-related macular degeneration (nvAMD) drives the principal cause of blindness in the elderly. While there is a robust genetic association between genes of innate immunity and AMD, genome-to-phenome relationships are low, suggesting a critical contribution of environmental triggers of disease. Possible insight comes from the observation that a past history of infection with pathogens such as Chlamydia pneumoniae, or other systemic inflammation, can predispose to nvAMD in later life. Using a mouse model of nvAMD with prior C. pneumoniae infection, endotoxin exposure, and genetic ablation of distinct immune cell populations, we demonstrated that peripheral infections elicited epigenetic reprogramming that led to a persistent memory state in retinal CX3CR1+ mononuclear phagocytes (MNPs). The immune imprinting persisted long after the initial inflammation had subsided and ultimately exacerbated choroidal neovascularization in a model of nvAMD. Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identified activating transcription factor 3 (ATF3) as a central mediator of retina-resident MNP reprogramming following peripheral inflammation. ATF3 polarized MNPs toward a reparative phenotype biased toward production of proangiogenic factors in response to subsequent injury. Therefore, a past history of bacterial endotoxin-induced inflammation can lead to immunological reprograming within CNS-resident MNPs and aggravate pathological angiogenesis in the aging retina.},
}
@article {pmid36786498,
year = {2023},
author = {Pan, J and Ho, S and Ly, A and Kalloniatis, M and Sowmya, A},
title = {Drusen-aware model for age-related macular degeneration recognition.},
journal = {Ophthalmic &amp; physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {43},
number = {4},
pages = {668-679},
pmid = {36786498},
issn = {1475-1313},
mesh = {Humans ; *Retinal Drusen/diagnosis ; *Macular Degeneration/diagnosis ; Retina ; Algorithms ; ROC Curve ; },
abstract = {INTRODUCTION: The purpose of this study was to build an automated age-related macular degeneration (AMD) colour fundus photography (CFP) recognition method that incorporates confounders (other ocular diseases) and normal age-related changes by using drusen masks for spatial feature supervision.<br><br>METHODS: A range of clinical sources were used to acquire 7588 CFPs. Contrast limited adaptive histogram equalisation was used for pre-processing. ResNet50 was used as the backbone network, and a spatial attention block was added to integrate prior knowledge of drusen features into the backbone. The evaluation metrics used were sensitivity, specificity and F1 score, which is the harmonic mean of precision and recall (sensitivity) and area under the receiver-operating characteristic (AUC). Fivefold cross-validation was performed, and the results compared with four other methods.<br><br>RESULTS: Excellent discrimination results were obtained with the algorithm. On the public dataset (n&#xa0;=&#xa0;6565), the proposed method achieved a mean (SD) sensitivity of 0.54 (0.09), specificity of 0.99 (0.00), F1 score of 0.62 (0.06) and AUC of 0.92 (0.02). On the private dataset (n&#xa0;=&#xa0;1023), the proposed method achieved a sensitivity of 0.92 (0.02), specificity of 0.98 (0.01), F1 score of 0.92 (0.01) and AUC of 0.98 (0.01).<br><br>CONCLUSION: The proposed drusen-aware model outperformed baseline and other vessel feature-based methods in F1 and AUC on the AMD/normal CFP classification task and achieved comparable results on datasets that included other diseases that often confound classification. The method also improved results when a five-category grading protocol was used, thereby reflecting discriminative ability of the algorithm within a real-life clinical setting.},
}
@article {pmid36782163,
year = {2023},
author = {Hanumunthadu, D and Saleh, A and Florea, D and Balaskas, K and Keane, PA and Aslam, T and Patel, PJ},
title = {Biomarkers of macular neovascularisation activity using optical coherence tomography angiography in treated stable neovascular age related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {68},
pmid = {36782163},
issn = {1471-2415},
support = {MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Prospective Studies ; *Choroidal Neovascularization/diagnosis/drug therapy ; *Macular Degeneration/diagnosis/drug therapy ; Biomarkers ; *Wet Macular Degeneration/diagnosis/drug therapy ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {BACKGROUND: The aim of this study was to describe features of disease activity in patients with treated stable macular neovascularisation (MNV) in neovascular age related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA).<br><br>METHODS: Thirty-two eyes of 32 patients with nAMD were included in this prospective, observational study. These patients were undergoing treatment with aflibercept on a treat-and-extend regimen attending an extension to a 12-week treatment interval.<br><br>RESULTS: All subjects had no macular haemorrhage and no structural OCT markers of active MNV activity at the index 12-week treatment extension visit. 31/32 OCTA images were gradeable without significant imaging artefact. The mean MNV size was 3.6mm[2]&#x2009;&#xb1;&#x2009;4.6mm[2] and 27 (87.1%) had detectable MNV blood flow. 29/31 (93.5%) subjects had MNV with mature phenotypes including 10 non-specific, 10 tangle and 3 deadtree phenotypes. MNV halo and MNV central feeder vessel were noted in 18 (58.1%) and 19 (61.3%) of subjects respectively; only 1 (3.2%) subject was noted to have a MNV capillary fringe.<br><br>CONCLUSIONS: MNV blood flow is still detectable using OCTA in the majority of subjects in this study with treated stable MNV. OCTA features associated included MNV mature phenotype, MNV feeder vessel, MNV halo and absence of capillary fringe.},
}
@article {pmid36781630,
year = {2023},
author = {Morga, A and Chamberlain, CX and Meyers, O and Roberts, C and Gaspar, L and Su, J},
title = {Content Validity and Cognitive Debriefing of a Patient-Reported Outcome Instrument Evaluating Symptoms and Disease Impact in Patients with Geographic Atrophy.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {2},
pages = {1181-1193},
pmid = {36781630},
issn = {2193-8245},
abstract = {INTRODUCTION: Geographic atrophy (GA) occurs in the later stages of dry age-related macular degeneration (AMD) and impairs visual acuity, eventually causing permanent blindness in some patients and impacting patient quality of life. Patient-reported outcome (PRO) measures that assess the experience of patients with visual impairment do not sufficiently capture all concepts salient to patients with GA. In this study the experience of patients with GA secondary to dry AMD was evaluated, and items from the novel 10-item Visual Impairment Symptom Severity Assessment (VISSA-10) PRO instrument were mapped to salient symptoms to assess its content validity, ease of use, and relevance.<br><br>METHODS: Concept elicitation interviews were conducted with patients with GA to determine salient symptoms and impacts of GA, and a conceptual model was developed to reflect these. The items in the VISSA-10 instrument were then mapped onto the salient symptoms included in this conceptual model. Cognitive debriefing interviews were also conducted with the same cohort to determine the comprehensiveness and comprehensibility of the instrument, and to qualitatively assess levels of change considered meaningful by patients.<br><br>RESULTS: In total, 25 symptoms and 36 impacts were reported by 19 patients with GA, with seven symptoms and 11 impacts identified as salient. Of these, 12 symptoms and 15 impacts reported were not included in a previously published conceptual model for patients with dry AMD. Overall, eight of the ten items from the VISSA-10 instrument mapped to salient symptoms reported by patients with GA. All patients reported that the instrument was clear and easy to understand.<br><br>CONCLUSIONS: The VISSA-10 instrument was shown to be content valid, clear, and comprehensible, with sufficient concept coverage to measure the experience of patients with GA. Although further quantitative validation is required, this instrument has demonstrated potential for implementation in future clinical trials to evaluate the efficacy of new treatments for GA.},
}
@article {pmid36781222,
year = {2023},
author = {Palanker, D},
title = {Electronic Retinal Prostheses.},
journal = {Cold Spring Harbor perspectives in medicine},
volume = {13},
number = {8},
pages = {},
pmid = {36781222},
issn = {2157-1422},
support = {P30 EY026877/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Visual Prosthesis ; Neurons ; Electric Stimulation ; Electronics ; Retina ; },
abstract = {Retinal prostheses are a promising means for restoring sight to patients blinded by photoreceptor atrophy. They introduce visual information by electrical stimulation of the surviving inner retinal neurons. Subretinal implants target the graded-response secondary neurons, primarily the bipolar cells, which then transfer the information to the ganglion cells via the retinal neural network. Therefore, many features of natural retinal signal processing can be preserved in this approach if the inner retinal network is retained. Epiretinal implants stimulate primarily the ganglion cells, and hence should encode the visual information in spiking patterns, which, ideally, should match the target cell types. Currently, subretinal arrays are being developed primarily for restoration of central vision in patients impaired by age-related macular degeneration (AMD), while epiretinal implants-for patients blinded by retinitis pigmentosa, where the inner retina is less preserved. This review describes the concepts and technologies, preclinical characterization of prosthetic vision and clinical outcomes, and provides a glimpse into future developments.},
}
@article {pmid36777624,
year = {2023},
author = {Yang, Y and Wang, Y and Liu, X and Deng, Y and Lu, J and Jiang, F and Nie, F and Peng, J and Peng, Q and Qin, Y},
title = {Network Pharmacology-Based Identification of Key Targets of Ziyin Mingmu Pills Acting on Age-Related Macular Degeneration.},
journal = {Evidence-based complementary and alternative medicine : eCAM},
volume = {2023},
number = {},
pages = {5933125},
pmid = {36777624},
issn = {1741-427X},
abstract = {OBJECTIVE: This study is designed to find out the molecular targets of effective Chinese medicine Ziyin Mingmu pills (ZMPs) in treating age-related macular degeneration (AMD) based on network pharmacology and experimental data.<br><br>METHODS: A comprehensive network pharmacology strategy that consists of three sequential modules (drug-disease target molecular docking, enrichment analysis, and external verification) was carried out to identify potential targets of ZMPs acting on AMD.<br><br>RESULTS: The active ingredients of ZMPs targeting 66 genes have effects on the process of AMD. GO and KEGG pathway enrichment analyses suggested that response to oxidative stress, regulation of angiogenesis, and lipid and atherosclerosis might serve as the most important signaling pathways in ZMPs for AMD treatment. Combined with the GSE29801 dataset for further analysis, two key genes, EGFR and VEGFA, were identified. Immune infiltration analysis showed that there was a strong association between EGFR and immune cell content. In addition, images were acquired following 24&#x2009;h in the scratch experiment showed that ZMPs can reduce the percentage of wound healing distance. The Western blot assay found that ZMPs increased the expression of EGFR and decreased the expression of VEGFA.<br><br>CONCLUSION: This study sheds light on some mechanisms of ZMP therapy for AMD, particularly the effect of ZMP on the oxidative stress in RPE and cell survival and angiogenesis in AMD. We propound ZMPs as a promising strategy to intervene in the process of AMD.},
}
@article {pmid36776999,
year = {2022},
author = {Mungmunpuntipantip, R and Wiwanitkit, V},
title = {Polymorphisms in CFI and ARMS genes and exudative age-related macular degeneration: Correspondence.},
journal = {Molecular biology research communications},
volume = {11},
number = {4},
pages = {187},
pmid = {36776999},
issn = {2345-2005},
}
@article {pmid36775060,
year = {2023},
author = {Mullin, NK and Voigt, AP and Boese, EA and Liu, X and Stone, EM and Tucker, BA and Mullins, RF},
title = {Transcriptomic and Chromatin Accessibility Analysis of the Human Macular and Peripheral Retinal Pigment Epithelium at the Single-Cell Level.},
journal = {The American journal of pathology},
volume = {193},
number = {11},
pages = {1750-1761},
pmid = {36775060},
issn = {1525-2191},
support = {F30 EY034009/EY/NEI NIH HHS/United States ; T32 GM139776/GM/NIGMS NIH HHS/United States ; P30 EY025580/EY/NEI NIH HHS/United States ; F30 EY031923/EY/NEI NIH HHS/United States ; R01 EY033331/EY/NEI NIH HHS/United States ; R01 EY033308/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Retinal Pigment Epithelium/metabolism ; Transcriptome/genetics ; Chromatin/genetics/metabolism ; Retina/pathology ; *Macular Degeneration/pathology ; *Retinal Diseases/pathology ; },
abstract = {Some human retinal diseases are characterized by pathology that is restricted to specific cell types and to specific regions of the eye. Several disease entities either selectively affect or spare the macula, the retina region at the center of the posterior pole. Photoreceptor cells in the macula are involved in high-acuity vision and require metabolic support from non-neuronal cell types. Some macular diseases involve the retinal pigment epithelium (RPE), an epithelial cell layer with several metabolic-support functions essential for the overlying photoreceptors. In the current study, the ways in which RPE confers region-specific disease susceptibility were determined by examining heterogeneity within RPE tissue from human donors. RPE nuclei from the macular and peripheral retina were profiled using joint single-nucleus RNA and ATAC sequencing. The expression of several genes differed between macular and peripheral RPE. Region-specific ATAC peaks were found, suggesting regulatory elements used exclusively by macular or peripheral RPE. Across anatomic regions, subpopulations of RPE were identified that appeared to have differential levels of expression of visual cycle genes. Finally, loci associated with age-related macular degeneration were examined for a better understanding of RPE-specific disease phenotypes. These findings showed variations in the regulation of gene expression in the human RPE by region and subpopulation, and provide a source for a better understanding of the molecular basis of macular disease.},
}
@article {pmid36773847,
year = {2023},
author = {Vasku, G and Peltier, C and He, Z and Thuret, G and Gain, P and Gabrielle, PH and Acar, N and Berdeaux, O},
title = {Comprehensive mass spectrometry lipidomics of human biofluids and ocular tissues.},
journal = {Journal of lipid research},
volume = {64},
number = {3},
pages = {100343},
pmid = {36773847},
issn = {1539-7262},
mesh = {Humans ; *Lipidomics/methods ; Mass Spectrometry/methods ; Chromatography, Liquid/methods ; Phospholipids ; *Macular Degeneration ; },
abstract = {Evaluating lipid profiles in human tissues and biofluids is critical in identifying lipid metabolites in dysregulated metabolic pathways. Due to various chemical characteristics, single-run lipid analysis has not yet been documented. Such approach is essential for analyzing pathology-related lipid metabolites. Age-related macular degeneration, the leading cause of vision loss in western countries, is emblematic of this limitation. Several studies have identified alterations in individual lipids but the majority are based on targeted approaches. In this study, we analyzed and identified approximately 500 lipid species in human biofluids (plasma and erythrocytes) and ocular tissues (retina and retinal pigment epithelium) using the complementarity of hydrophilic interaction liquid chromatography (HILIC) and reversed-phase chromatography (RPC), coupled to high-resolution mass spectrometry. For that, lipids were extracted from human eye globes and blood from 10 subjects and lipidomic analysis was carried out through analysis in HILIC and RPC, alternately. Furthermore, we illustrate the advantages and disadvantages of both techniques for lipid characterization. RPC showed greater sensitivity in hydrophobicity-based lipid separation, detecting diglycerides, triglycerides, cholesterol, and cholesteryl esters, whereas no signal of these molecules was obtained in HILIC. However, due to coelution, RPC was less effective in separating polar lipids like phospholipids, which were separated effectively in HILIC in both ionization modes. The complementary nature of these analytical approaches was essential for the detection and identification of lipid classes/subclasses, which can then provide distinct insights into lipid metabolism, a determinant of the pathophysiology of several diseases involving lipids, notably age-related macular degeneration.},
}
@article {pmid36771377,
year = {2023},
author = {Chen, YY and Chen, YJ},
title = {The Relationship between Dietary Calcium and Age-Related Macular Degeneration.},
journal = {Nutrients},
volume = {15},
number = {3},
pages = {},
pmid = {36771377},
issn = {2072-6643},
mesh = {Humans ; Aged ; *Calcium, Dietary ; Nutrition Surveys ; Cross-Sectional Studies ; *Macular Degeneration/epidemiology/etiology ; Minerals ; },
abstract = {BACKGROUND: Mineral element supplements are widely used in the older adult population. However, little is known of their impact on the progression of age-related macular degeneration (ARMD). The aim of this study was to examine the association between dietary micronutrients and ARMD in older adults.<br><br>METHODS: We enrolled 5227 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2008) in this cross-sectional study. ARMD was evaluated using an ophthalmic digital imaging system and digital camera. Mineral element consumption was collected using a 24-hour dietary recall. The association between mineral element use and the presence of ARMD was determined by multivariable logistic regression.<br><br>RESULTS: After adjusting for relevant variables, dietary calcium was negatively associated with ARMD (OR: 680, 95%CI: 0.482-0.960). In contrast to dietary form, serum concentration of calcium was not associated with ARMD. Moreover, increased dietary calcium was associated with reduced ARMD (OR: 0.684, 95%CI: 0.468-1.000).<br><br>CONCLUSION: A lower consumption of dietary calcium was significantly associated with a higher risk of ARMD. Further longitudinal studies are necessary to explore these findings.},
}
@article {pmid36771309,
year = {2023},
author = {de Koning-Backus, APM and Kiefte-de Jong, JC and van Rooij, JGJ and Amd-Life Team, and Uitterlinden, AG and Voortman, TG and Meester-Smoor, MA and Klaver, CCW},
title = {Lifestyle Intervention Randomized Controlled Trial for Age-Related Macular Degeneration (AMD-Life): Study Design.},
journal = {Nutrients},
volume = {15},
number = {3},
pages = {},
pmid = {36771309},
issn = {2072-6643},
support = {6.3.0.//Combined Ophthalmic Research Rotterdam/ ; 2016-19//Uitzicht/ ; 2020//Rotterdamse Stichting Blindenbelangen/ ; 2021-2024//Vitaminen op Recept/ ; },
mesh = {Humans ; *Life Style ; Antioxidants ; Genetic Testing ; Diet, Healthy ; *Macular Degeneration/prevention &amp; control/genetics ; },
abstract = {Age-related macular degeneration (AMD) has a strong genetic basis, but environmental factors such as smoking and a healthy diet can decrease the genetic fate by up to 50%. Current guidelines for clinical management include recommendations for a healthy lifestyle and antioxidant supplementation. However, many ophthalmologists do not inform their patients of this AMD-beneficial lifestyle. An important reason is the lack of trust that transition of lifestyle will be feasible in persons of advanced age and lack of methodology to measure lifestyle or its biological effects. To address these issues, we set up the lifestyle intervention study AMD-Life. It aims to investigate whether personalized risk-profiling (including genetic testing) and/or additional coaching can motivate patients to change their lifestyle. It also explores which biomarkers best reflect lifestyle change beneficial for AMD. The first year is a three-arm, self-contained open-label randomized clinical trial. A total of 150 AMD patients aged 55-85 years were randomized into three arms: (A) merely standard recommendations; (B) A conditions plus personalized risk profiling based on genetics and lifestyle, (C) B conditions plus coaching. The second year tests sustainability of lifestyle changes without active intervention. AMD-Life can provide further insight into the relevance of these interventions for the clinical management of AMD.},
}
@article {pmid36769787,
year = {2023},
author = {Toto, L and Ruggeri, ML and Evangelista, F and Trivigno, C and D'Aloisio, R and De Nicola, C and Viggiano, P and Doronzo, E and Di Nicola, M and Porreca, A and Mastropasqua, R},
title = {Choroidal and Retinal Imaging Biomarkers in Different Types of Macular Neovascularization.},
journal = {Journal of clinical medicine},
volume = {12},
number = {3},
pages = {},
pmid = {36769787},
issn = {2077-0383},
abstract = {BACKGROUND: The aim of this study was to investigate optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in patients with neovascular age-related macular degeneration (nAMD) and macular neovascularization (MNV) type 1, type 2, and type 3.<br><br>METHODS: In this retrospective study, 105 treatment-na&#xef;ve eyes of 105 patients (60 men and 45 women) with a definite diagnosis of active nAMD and MNV of different types and 105 frequency-matched age and gender healthy subjects were evaluated (61 men and 44 women). All subjects underwent a full ophthalmic examination and multimodal imaging assessment, including spectral domain (SD) OCT and OCTA. The main outcome measures were choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), and outer retina to choriocapillaris (ORCC) MNV flow area (ORCCFA).<br><br>RESULTS: Significant differences were found in terms of CVI, CMT, and ORCCFA between MNV 1 and the two other groups. CVI was significantly different between MNV 1 and healthy control patients (p < 0.001) and between MNV 1 and MNV 2 (p < 0.001). ORCCFA and CMT were significantly different between MNV1 and MNV2 (p < 0.005). The difference in subfoveal CT between the three groups was not statistically significant (p = 0.458). A significant negative correlation was found between CVI and ORCCFA. Furthermore, CVI showed a positive correlation with subfoveal CT.},
}
@article {pmid36769653,
year = {2023},
author = {Han, J and Choi, S and Park, JI and Hwang, JS and Han, JM and Ko, J and Yoon, J and Hwang, DD},
title = {Detecting Macular Disease Based on Optical Coherence Tomography Using a Deep Convolutional Network.},
journal = {Journal of clinical medicine},
volume = {12},
number = {3},
pages = {},
pmid = {36769653},
issn = {2077-0383},
support = {NRF-2020K2A9A2A11103842//National Research Foundation of Korea/ ; 2021R1A4A3022102//National Research Foundation of Korea/ ; },
abstract = {Neovascular age-related macular degeneration (nAMD) and central serous chorioretinopathy (CSC) are two of the most common macular diseases. This study proposes a convolutional neural network (CNN)-based deep learning model for classifying the subtypes of nAMD (polypoidal choroidal vasculopathy, retinal angiomatous proliferation, and typical nAMD) and CSC (chronic CSC and acute CSC) and healthy individuals using single spectral-domain optical coherence tomography (SD-OCT) images. The proposed model was trained and tested using 6063 SD-OCT images from 521 patients and 47 healthy participants. We used three well-known CNN architectures (VGG-16, VGG-19, and ResNet) and two customized classification layers. Additionally, transfer learning and mix-up-based data augmentation were applied to improve robustness and accuracy. Our model demonstrated high accuracies of 99.7% and 91.1% in the nAMD and CSC classification and retinopathy (nAMD and CSC) subtype classification, including normal participants, respectively. Furthermore, we performed an external test to compare the classification accuracy with that of eight ophthalmologists, and our model showed the highest accuracy. The region determined to be important for classification by the model was confirmed using gradient-weighted class activation mapping. The model's clinical criteria were similar to that of the ophthalmologists.},
}
@article {pmid36769075,
year = {2023},
author = {Ultimo, A and Orzaez, M and Santos-Martinez, MJ and Martínez-Máñez, R and Marcos, MD and Sancenón, F and Ruiz-Hernández, E},
title = {High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery.},
journal = {International journal of molecular sciences},
volume = {24},
number = {3},
pages = {},
pmid = {36769075},
issn = {1422-0067},
support = {758887/ERC_/European Research Council/International ; 952259//Community Research and Development Information Service/ ; RTI2018-100910-B-C41//Spanish Government/ ; RTI2018-101599-B-C22//Spanish Government/ ; PROMETEO2018/024//Generalitat Valenciana/ ; 713567/ERC_/European Research Council/International ; },
mesh = {RNA, Small Interfering/metabolism ; *Vascular Endothelial Growth Factor A/genetics/metabolism ; Silicon Dioxide/metabolism ; Retinal Pigment Epithelium/metabolism ; *Nanoparticles ; },
abstract = {The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter.},
}
@article {pmid36768958,
year = {2023},
author = {Hyttinen, JMT and Blasiak, J and Kaarniranta, K},
title = {Non-Coding RNAs Regulating Mitochondrial Functions and the Oxidative Stress Response as Putative Targets against Age-Related Macular Degeneration (AMD).},
journal = {International journal of molecular sciences},
volume = {24},
number = {3},
pages = {},
pmid = {36768958},
issn = {1422-0067},
support = {5503770//Kuopio University Hospital/ ; 296840//Academy of Finland/ ; 2017/27/B/NZ3/00872//National Science Centre, Poland/ ; },
mesh = {Aged ; Humans ; *Antioxidants/metabolism ; *Macular Degeneration/metabolism ; Mitochondria/genetics/metabolism ; Oxidative Stress/genetics ; Quality of Life ; Retinal Pigment Epithelium/metabolism ; RNA, Long Noncoding/genetics ; },
abstract = {Age-related macular degeneration (AMD) is an ever-increasing, insidious disease which reduces the quality of life of millions of elderly people around the world. AMD is characterised by damage to the retinal pigment epithelium (RPE) in the macula region of the retina. The origins of this multi-factorial disease are complex and still not fully understood. Oxidative stress and mitochondrial imbalance in the RPE are believed to be important factors in the development of AMD. In this review, the regulation of the mitochondrial function and antioxidant stress response by non-coding RNAs (ncRNAs), newly emerged epigenetic factors, is discussed. These molecules include microRNAs, long non-coding RNAs, and circular non-coding RNAs. They act mainly as mRNA suppressors, controllers of other ncRNAs, or by interacting with proteins. We include here examples of these RNA molecules which affect various mitochondrial processes and antioxidant signaling of the cell. As a future prospect, the possibility to manipulate these ncRNAs to strengthen mitochondrial and antioxidant response functions is discussed. Non-coding RNAs could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, either by suppressing or increasing their expression. In addition to AMD, it is possible that non-coding RNAs could be regulators in other oxidative stress-related degenerative diseases.},
}
@article {pmid36768783,
year = {2023},
author = {Koraneeyakijkulchai, I and Phumsuay, R and Thiyajai, P and Tuntipopipat, S and Muangnoi, C},
title = {Anti-Inflammatory Activity and Mechanism of Sweet Corn Extract on Il-1β-Induced Inflammation in a Human Retinal Pigment Epithelial Cell Line (ARPE-19).},
journal = {International journal of molecular sciences},
volume = {24},
number = {3},
pages = {},
pmid = {36768783},
issn = {1422-0067},
support = {Mahidol University//Mahidol University/ ; },
mesh = {Animals ; Humans ; Aged ; *NF-kappa B/metabolism ; Zea mays/metabolism ; Retinal Pigment Epithelium/metabolism ; Inflammation/metabolism ; Anti-Inflammatory Agents/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is an eye disease associated with aging. Development of AMD is related to degeneration and dysfunction of the retinal pigment epithelium (RPE) caused by low-grade chronic inflammation in aged RPE cells leading to visual loss and blindness. Sweet corn is a good source of lutein and zeaxanthin, which were reported to exert various biological activities, including anti-inflammatory activity. The present study aims to investigate the anti-inflammatory activity and mechanisms of SCE to inhibit the production of inflammatory biomarkers related to AMD development. Cells were pretreated with SCE for 1 h followed by stimulation with IL-1β for another 24 h. The results demonstrated that SCE attenuated IL-1β-induced production of IL-6, IL-8, and MCP-1 and the expression of ICAM-1 and iNOS in a dose-dependent manner. In addition, SCE suppressed the phosphorylation of ERK1/2, SAPK/JNK, p38, and NF-κB (p65) in IL-1β-stimulated ARPE-19 cells. These results proved that SCE protected ARPE-19 cells from IL-1β-induced inflammation by inhibiting inflammatory markers partly via suppressing the activation of MAPK and NF-κB signaling pathways. Overall, SCE is a potential agent for the prevention of AMD development, which should be further evaluated in animals.},
}
@article {pmid36768552,
year = {2023},
author = {Dörschmann, P and Kopplin, G and Roider, J and Klettner, A},
title = {Interaction of High-Molecular Weight Fucoidan from Laminaria hyperborea with Natural Functions of the Retinal Pigment Epithelium.},
journal = {International journal of molecular sciences},
volume = {24},
number = {3},
pages = {},
pmid = {36768552},
issn = {1422-0067},
support = {310167//Norwegian Research Council through the Fucomed project/ ; },
mesh = {Swine ; Animals ; *Retinal Pigment Epithelium/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; *Laminaria/metabolism ; Interleukin-8/metabolism ; Molecular Weight ; Interleukin-6/metabolism ; Polysaccharides/pharmacology/metabolism ; Vascular Endothelial Growth Factors/metabolism ; Cells, Cultured ; },
abstract = {Fucoidans are polysaccharides and constituents of cell walls of brown algae such as Laminaria hyperborea (LH). They exhibit promising effects regarding age-related macular degeneration (AMD). However, the safety of this compound needs to be assured. The focus of this study lies on influences of an LH fucoidan on the retinal pigment epithelium (RPE). The high-molecular weight LH fucoidan Fuc1 was applied to primary porcine RPE cells, and a tetrazolium (MTT) cell viability assay was conducted. Further tests included a scratch assay to measure wound healing, Western blotting to measure expression of retinal pigment epithelium-specific 65 kDa protein (RPE65), as well as immunofluorescence to measure uptake of opsonized fluorescence beads into RPE cells. Lipopolysaccharide was used to proinflammatorily activate the RPE, and interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion was measured. RPE/choroid cultures were used to assess vascular endothelial growth factor (VEGF) secretion. Real-time polymerase chain reaction (real-time PCR) was performed to detect the gene expression of 91 different genes in a specific porcine RPE gene array. Fuc1 slightly reduced wound healing, but did not influence cell viability, phagocytosis or RPE65 expression. Fuc1 lowered IL-6, IL-8 and VEGF secretion. Furthermore, Fuc1 did not change tested RPE genes. In conclusion, Fuc1 does not impair RPE cellular functions and shows antiangiogenic and anti-inflammatory activities, which indicates its safety and strengthens its suitability concerning ocular diseases.},
}
@article {pmid36764668,
year = {2023},
author = {Neffendorf, JE and Mare, T and Simpson, ARH and Soare, C and Kirthi, V and Sharpe, CC and Jackson, TL},
title = {Effect of intravitreal anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration on renal function.},
journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association},
volume = {38},
number = {7},
pages = {1770-1772},
doi = {10.1093/ndt/gfad035},
pmid = {36764668},
issn = {1460-2385},
mesh = {Humans ; *Endothelial Growth Factors/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; *Macular Degeneration/drug therapy ; Kidney/physiology ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Intravitreal Injections ; Treatment Outcome ; },
}
@article {pmid36763979,
year = {2023},
author = {Fragiotta, S and Parravano, M and Costanzo, E and De Geronimo, D and Varano, M and Fernández-Avellaneda, P and Freund, KB},
title = {SUBRETINAL LIPID GLOBULES AN EARLY BIOMARKER OF MACULAR NEOVASCULARIZATION IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {6},
pages = {913-922},
doi = {10.1097/IAE.0000000000003760},
pmid = {36763979},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis ; *Choroidal Neovascularization/diagnosis ; Tomography, Optical Coherence/methods ; Biomarkers ; Lipids ; *Wet Macular Degeneration/diagnosis ; },
abstract = {PURPOSE: To explore the association between subretinal lipid globules (SLGs) detected in eyes with intermediate age-related macular degeneration with the presence of nonexudative macular neovascularization.<br><br>METHODS: This was a retrospective analysis of 113 consecutive patients with bilateral intermediate age-related macular degeneration (226 eyes) followed for a least 6 months. All eyes underwent multimodal imaging with fundus autofluorescence, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Subretinal lipid globules were identified on spectral-domain optical coherence tomography as round hyporeflective lesions measuring 31 to 157 &#xb5; m located between the ellipsoid zone and the retinal pigment epithelium/Bruch membrane complex. Nonexudative macular neovascularization was detected with optical coherence tomography angiography. The features of NE-MNV lesions detected in eyes with SLGs were compared with those in eyes without SLGs.<br><br>RESULTS: Subretinal lipid globules were identified in 15 eyes of which 14 eyes (93.3%) demonstrated NE-MNV on optical coherence tomography angiography. In the remaining 98 eyes without SLGs, 18 (18.4%) displayed NE-AMD on optical coherence tomography angiography. The macular neovascularization area was larger in the SLG subgroup (+0.38 vs. +0.21 mm 2 , P = 0.008) and showed faster horizontal growth (+727 &#xb5; m, CI 95% 250.4, 1,205.4) than MNV in eyes without SLGs (+64.9 &#xb5; m, CI 95%, 24.3, 154) on optical coherence tomography B-scans. After a mean of 11.6 months, the conversion rate to exudative MNV was similar between eyes with SLGs and those without SLGs [8/26 (38.5%) versus 3/13 (27.3%), P = 0.56)].<br><br>CONCLUSION: The detection of SLGs in eyes with intermediate age-related macular degeneration was strongly correlated with the presence of NE-MNV. Although these MNV lesions were larger and grew faster than NE-MNV detected in eyes lacking SLGs, the rates of conversion to exudative MNV appeared similar.},
}
@article {pmid36763052,
year = {2023},
author = {Brandl, C and Zimmermann, ME and Herold, JM and Helbig, H and Stark, KJ and Heid, IM},
title = {Photostress Recovery Time as a Potential Predictive Biomarker for Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {2},
pages = {15},
pmid = {36763052},
issn = {2164-2591},
mesh = {Humans ; Aged ; Cross-Sectional Studies ; *Macular Degeneration/diagnosis ; Retina ; Visual Acuity ; Biomarkers ; },
abstract = {PURPOSE: The purpose of this study was to assess recovery time following photostress and its association with age-related macular degeneration (AMD) cross-sectionally and longitudinally in an elderly population-based cohort.<br><br>METHODS: We analyzed photostress recovery time (PRT) and AMD in >1800 AugUR study participants aged 70+ years. On color fundus images from baseline and 3-year follow-up, presence of AMD was graded manually (Three Continent AMD Consortium Severity Scale). Visual acuity (VA) was assessed via Early Treatment Diabetic Retinopathy Study (ETDRS) charts. After a 30-second bleaching of the macular region via direct ophthalmoscope, PRT was measured as the seconds to regain VA.<br><br>RESULTS: First, we analyzed 1208 AugUR participants cross-sectionally (288 with early AMD, and 78 with late AMD). Prolonged PRT was associated with early and late AMD versus no AMD (median PRT = 119.5, 198.0 versus 80.0 seconds, respectively; logistic regression odds ratio [OR] = 1.109-1.165 per 10 seconds, P values < 0.0001). Sensitivity analyses using alternative models or restricting to participants after cataract surgery revealed similar ORs. Second, the association was confirmed in an independent cross-sectional AugUR sample (n = 486). Third, in longitudinal analysis of 233 AugUR participants without AMD, prolonged PRT was associated with incident AMD ascertained 3 years later (follow-up time = 3.2 &#xb1; 0.2 years, OR = 1.112-1.162 per 10 seconds, P < 0.05). Overall, we demonstrate a significant association of prolonged PRT with AMD cross-sectionally and longitudinally in elderly individuals.<br><br>CONCLUSIONS: Prolonged PRT might capture retinal function impairment after cell damage before early AMD is visible via color fundus imaging.<br><br>TRANSLATIONAL RELEVANCE: Our results suggest PRT as quantitative predictive biomarker for incident AMD, making it potentially worthwhile also for clinical care.},
}
@article {pmid36761776,
year = {2023},
author = {Dobó, J and Gál, P and Geisbrecht, BV},
title = {Editorial: Complement: Latest developments regarding structure, mechanism, and connections to other proteolytic pathways.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1144038},
doi = {10.3389/fimmu.2023.1144038},
pmid = {36761776},
issn = {1664-3224},
support = {R35 GM140852/GM/NIGMS NIH HHS/United States ; },
mesh = {*Complement System Proteins ; },
}
@article {pmid36761168,
year = {2022},
author = {Zong, Y and Kamoi, K and Kurozumi-Karube, H and Zhang, J and Yang, M and Ohno-Matsui, K},
title = {Safety of intraocular anti-VEGF antibody treatment under in vitro HTLV-1 infection.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {1089286},
pmid = {36761168},
issn = {1664-3224},
mesh = {Adult ; Humans ; *Human T-lymphotropic virus 1 ; NF-kappa B ; *HTLV-I Infections ; *Paraparesis, Tropical Spastic ; Cytokines ; Proviruses ; },
abstract = {INTRODUCTION: HTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1-associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti-vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF165, the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF165 is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection in vitro.<br><br>METHODS: We used MT2 and TL-Om1 cells as HTLV-1-infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1-infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments.<br><br>RESULTS: Anti-VEGF antibody treatment had no effect on activated NF-&#x3ba;B production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-&#x3ba;B, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1-infected T cells.<br><br>CONCLUSION: This preliminary in vitro assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1-related inflammation and thus may be safe for use.},
}
@article {pmid36760065,
year = {2023},
author = {Vukicevic, M and McGuinness, MB and Jaross, N},
title = {Real-World Investigation of Impact of Retinal Fluid in Treatment Naïve Eyes Treated with Anti-VEGF for Neovascular Age-Related Macular Degeneration.},
journal = {Seminars in ophthalmology},
volume = {38},
number = {6},
pages = {592-597},
doi = {10.1080/08820538.2023.2176239},
pmid = {36760065},
issn = {1744-5205},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Treatment Outcome ; Retina ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {BACKGROUND: Traditionally, visual acuity gain and central retinal thickness have been used to measure outcomes when investigating the efficacy of vascular endothelial growth factor (VEGF) inhibitors for patients with neovascular age-related macular degeneration (nARMD). However, localization of retinal fluid may offer additional prognostic value for treatment. The primary aim of this retrospective clinical audit was to investigate whether the presence and location of subretinal fluid has an effect on the visual outcomes of treatment naïve patients with nARMD treated in the real-world setting with VEGF inhibitors. Secondary aims included investigation of change to visual and anatomical outcomes and investigation of the dosing schedule.<br><br>METHODS: Retrospective observational study of patients attending one suburban and one regional ophthalmology clinic requiring treatment with VEGF inhibitors for nARMD using single-user non-identifiable data from the Fight Retinal Blindness! Registry from 2014 to 2020. Visual acuity (VA) and central subfield thickness (CST) were recorded at baseline, 3, 6, 12 and 24&#xa0;months.<br><br>RESULTS: Forty-nine eyes of 42 treatment na&#xef;ve patients were included for analysis (aged 62-89&#xa0;years). Almost half (49%) presented with a combination of intra- and subretinal fluid at baseline. Intraretinal fluid was present in 75% of eyes but decreased to 22.7% of eyes by 24&#xa0;months. VA at baseline was 55 letters, and this improved by 6 letters. The change in VA from baseline to 3, 6 and 12&#xa0;months was statistically significant (p&#xa0;<&#xa0;.05). The mean change in CST from baseline to 3&#xa0;months was significant (-76&#xa0;&#xb5;m). This change was also observed at the other milestones (p&#xa0;<&#xa0;.001).<br><br>CONCLUSIONS: The findings of this study suggest that allowing some subretinal fluid to remain will not affect treatment outcomes.},
}
@article {pmid36758462,
year = {2023},
author = {Rathore, S and Goté, JT and Brafford, M and Morehouse, NI and Buschbeck, EK and Stowasser, A},
title = {Nutrition-induced macular-degeneration-like photoreceptor damage in jumping spider eyes.},
journal = {Vision research},
volume = {206},
number = {},
pages = {108185},
doi = {10.1016/j.visres.2023.108185},
pmid = {36758462},
issn = {1878-5646},
mesh = {Animals ; Humans ; *Macular Degeneration ; Retina/pathology ; *Retinal Degeneration/pathology ; *Spiders ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in humans. Despite its prevalence and medical significance, many aspects of AMD remain elusive and treatment options are limited. Here, we present data that suggest jumping spiders offer a unique opportunity for understanding the fundamentals underlying retinal degeneration, thereby shedding light on a process that impacts millions of people globally. Using a micro-ophthalmoscope and histological evidence, we demonstrate that significant photoreceptor damage can occur during development in the image-forming anterior lateral eyes of the jumping spider Phidippus audax. Furthermore, we find that this photoreceptor degeneration is exacerbated by inadequate nutrition and is most prevalent in the high-density region of the retina, like AMD in humans. This suggests that similar to those in vertebrates, the retinas in P. audax are challenged to meet high-energy cellular demands.},
}
@article {pmid36756537,
year = {2023},
author = {Enoch, J and Ghulakhszian, A and Sekhon, M and Crabb, DP and Taylor, DJ and Dinah, C},
title = {Towards a Therapy for Geographic Atrophy: A Patient's Experience.},
journal = {Patient preference and adherence},
volume = {17},
number = {},
pages = {299-310},
pmid = {36756537},
issn = {1177-889X},
abstract = {PURPOSE: Geographic atrophy (GA) is the advanced form of the non-neovascular (dry) type of age-related macular degeneration. Presently, GA cannot be treated. However, new therapies administered by intravitreal injection are in late-stage development. These can slow down, but do not stop or reverse, GA progression. The acceptability of these emerging therapies to people with GA is currently unknown. The present case study explores the perspectives of a person living with GA who took part in the terminated Phase 3 clinical trial of Lampalizumab, a candidate intravitreal treatment for GA. We explored this patient's perspective on the retrospective acceptability of regular Lampalizumab injections, and the prospective acceptability of future intravitreal therapies for GA.<br><br>PATIENTS AND METHODS: A 78-year-old woman living in the UK was recruited as part of a mixed-methods pilot study and interviewed by telephone, regarding: her experience of the Lampalizumab trial injections; and her thoughts regarding emerging intravitreal therapies for GA. The Framework Method was used for initial inductive analysis of the interview transcript. Subsequently, deductive analysis was undertaken, informed by the Theoretical Framework of Acceptability (TFA).<br><br>RESULTS: For this participant, intravitreal injections in the Lampalizumab trial were acceptable, although streamlining processes within the clinic would have improved the patient experience. Regarding prospective acceptability of new intravitreal therapies, the participant considered a delay in progression of GA a valuable goal. Potential discomfort, anxiety and inconvenience associated with regular intravitreal injections would be acceptable in the context of preserving her vision for as long as possible.<br><br>CONCLUSION: Analysis of one participant's experience demonstrates the value of exploring GA patients' unique views on the acceptability of new intravitreal treatments. Larger prospective studies will provide more insight that help to optimise treatment design and delivery, thereby maximising likelihood of adherence and persistence when these therapies eventually arrive in clinic.},
}
@article {pmid36756225,
year = {2023},
author = {Li, H and Wang, L and Shao, M and Ren, M and Zhang, W and Zhou, J and Wang, J},
title = {Pirfenidone Attenuates the EMT Process and the Secretion of VEGF in TGF-β2-Induced ARPE-19 Cells via Inhibiting the Activation of the NF-κB/Snail Signaling Pathway.},
journal = {Journal of ophthalmology},
volume = {2023},
number = {},
pages = {4798071},
pmid = {36756225},
issn = {2090-004X},
abstract = {AIM: Pirfenidone (PFD), an antifibrotic drug, has various beneficial functions such as antioxidant, antifibrotic, and anti-inflammatory effects. This study aimed to explore the molecular mechanisms underlying how PFD modulates retinal pigment epithelial (RPE) cells involved in neovascularization and subretinal fibrosis.<br><br>METHODS: ARPE-19&#x2009;cell lines were treated with transforming growth factor-beta 2 (TGF-&#x3b2;2) alone or in combination with PFD. RPE cell viability, as a consequence of PFD use, was determined by the CCK-8 assay. Cell migration was assessed by the wound closure assay and quantified by the Image J software. Protein expression of the following markers was measured by the western blot analysis: an epithelial cell marker and E-cadherin; mesenchymal cell markers, fibronectin, matrix metalloprotein-9 (MMP-9), and alpha-smooth muscle actin (&#x3b1;-SMA); a fibrotic marker and connective tissue growth factor (CTGF); an angiogenesis marker and vascular endothelial growth factor (VEGF); NF-&#x3ba;B/Snail. The mRNA levels of fibronectin and &#x3b1;-SMA were determined by quantitative real-time PCR. VEGF was quantitatively measured by the enzyme-linked immunosorbent assay.<br><br>RESULTS: The cell viability assay revealed that PFD had no significant cytotoxic effect on RPE cells at concentrations of less than 1&#x2009;mg/mL. The cell scratch assay showed that TGF-&#x3b2;2 stimulation significantly improved the migration of RPE cells and that PFD attenuated this effect. PFD significantly inhibited the TGF-&#x3b2;2-induced protein expression of E-cadherin and increased the TGF-&#x3b2;2-induced protein expression of fibronectin, MMP-9, &#x3b1;-SMA, CTGF, and VEGF in ARPE-19&#x2009;cells. The mRNA expression of fibronectin and &#x3b1;-SMA was inhibited by PFD in TGF-&#x3b2;2-inducedARPE-19&#x2009;cells. Additionally, the increased intracellular and supernatant expression of VEGF protein was suppressed by PFD. Mechanistically, RPE cells treated with PFD&#x2009;+&#x2009;TGF-&#x3b2;2 exhibited a decrease in phosphorylation of the NF-&#x3ba;B P65 subunit and activation of Snail, compared with the RPE cells treated with TGF-&#x3b2;2 alone.<br><br>CONCLUSION: PFD ameliorated TGF-&#x3b2;2-induced neovascularization and fibrosis by suppressing the NF-&#x3ba;B/Snail signaling pathway. Therefore, PFD may be a potential drug in the treatment of age-related macular degeneration.},
}
@article {pmid36755888,
year = {2023},
author = {Xie, L and Vaghefi, E and Yang, S and Han, D and Marshall, J and Squirrell, D},
title = {Automation of Macular Degeneration Classification in the AREDS Dataset, Using a Novel Neural Network Design.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {455-469},
pmid = {36755888},
issn = {1177-5467},
abstract = {PURPOSE: To create an ensemble of Convolutional Neural Networks (CNNs), capable of detecting and stratifying the risk of progressive age-related macular degeneration (AMD) from retinal photographs.<br><br>DESIGN: Retrospective cohort study.<br><br>METHODS: Three individual CNNs are trained to accurately detect 1) advanced AMD, 2) drusen size and 3) the presence or otherwise of pigmentary abnormalities, from macular centered retinal images were developed. The CNNs were then arranged in a "cascading" architecture to calculate the Age-related Eye Disease Study (AREDS) Simplified 5-level risk Severity score (Risk Score 0 - Risk Score 4), for test images. The process was repeated creating a simplified binary "low risk" (Scores 0-2) and "high risk" (Risk Score 3-4) classification.<br><br>PARTICIPANTS: There were a total of 188,006 images, of which 118,254 images were deemed gradable, representing 4591 patients, from the AREDS1 dataset. The gradable images were split into 50%/25%/25% ratios for training, validation and test purposes.<br><br>MAIN OUTCOME MEASURES: The ability of the ensemble of CNNs using retinal images to predict an individual's risk of experiencing progression of their AMD based on the AREDS 5-step Simplified Severity Scale.<br><br>RESULTS: When assessed against the 5-step Simplified Severity Scale, the results generated by the ensemble of CNN's achieved an accuracy of 80.43% (quadratic kappa 0.870). When assessed against a simplified binary (Low Risk/High Risk) classification, an accuracy of 98.08%, sensitivity of &#x2265;85% and specificity of &#x2265;99% was achieved.<br><br>CONCLUSION: We have created an ensemble of neural networks, trained on the AREDS 1 dataset, that is able to accurately calculate an individual's score on the AREDS 5-step Simplified Severity Scale for AMD. If the results presented were replicated, then this ensemble of CNNs could be used as a screening tool that has the potential to significantly improve health outcomes by identifying asymptomatic individuals who would benefit from AREDS2 macular supplements.},
}
@article {pmid36755326,
year = {2023},
author = {Augustin, S and Lam, M and Lavalette, S and Verschueren, A and Blond, F and Forster, V and Przegralek, L and He, Z and Lewandowski, D and Bemelmans, AP and Picaud, S and Sahel, JA and Mathis, T and Paques, M and Thuret, G and Guillonneau, X and Delarasse, C and Sennlaub, F},
title = {Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
pages = {28},
pmid = {36755326},
issn = {1742-2094},
support = {ANR-18-CE14-0031-02//Agence Nationale de la Recherche/ ; ANR-10-LABX-65//LABEX LIFESENSES/ ; ANR-18-IAHU-0001//IHU FOReSIGHT/ ; },
mesh = {Humans ; Animals ; Mice ; *CD47 Antigen/metabolism ; Retinal Pigment Epithelium/metabolism ; *Macular Degeneration/metabolism ; Retina/metabolism ; Tomography, Optical Coherence/methods ; },
abstract = {Retinal melanosome/melanolipofuscin-containing cells (MCCs), clinically visible as hyperreflective foci (HRF) and a highly predictive imaging biomarker for the progression of age-related macular degeneration (AMD), are widely believed to be migrating retinal pigment epithelial (RPE) cells. Using human donor tissue, we identify the vast majority of MCCs as melanophages, melanosome/melanolipofuscin-laden mononuclear phagocytes (MPs). Using serial block-face scanning electron microscopy, RPE flatmounts, bone marrow transplantation and in vitro experiments, we show how retinal melanophages form by the transfer of melanosomes from the RPE to subretinal MPs when the "don't eat me" signal CD47 is blocked. These melanophages give rise to hyperreflective foci in Cd47[-/-]-mice in vivo, and are associated with RPE dysmorphia similar to intermediate AMD. Finally, we show that Cd47 expression in human RPE declines with age and in AMD, which likely participates in melanophage formation and RPE decline. Boosting CD47 expression in AMD might protect RPE cells and delay AMD progression.},
}
@article {pmid36755014,
year = {2023},
author = {Zhou, J and Qiu, J and Song, Y and Liang, T and Liu, S and Ren, C and Song, X and Cui, L and Sun, Y},
title = {Pyroptosis and degenerative diseases of the elderly.},
journal = {Cell death &amp; disease},
volume = {14},
number = {2},
pages = {94},
pmid = {36755014},
issn = {2041-4889},
mesh = {Humans ; Aged ; *Pyroptosis/physiology ; *Caspases/metabolism ; Gasdermins ; Inflammasomes/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Neoplasm Proteins/metabolism ; Phosphate-Binding Proteins/metabolism ; },
abstract = {Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins of the gasdermin family. Widely recognized signaling cascades include the classical, non-classical, caspase-3-dependent gasdermin E and caspase-8-dependent gasdermin D pathways. Additional pyroptotic pathways have been subsequently reported. With the rising prevalence of advanced age, the role of pyroptosis in the degenerative diseases of the elderly has attracted increased research attention. This article reviews the primary mechanisms of pyroptosis and summarizes progress in the research of degenerative diseases of the elderly such as presbycusis, age-related macular degeneration, Alzheimer's disease, intervertebral disc degeneration, and osteoarthritis.},
}
@article {pmid36754174,
year = {2023},
author = {Jackson, TL and Slakter, J and Buyse, M and Wang, K and Dugel, PU and Wykoff, CC and Boyer, DS and Gerometta, M and Baldwin, ME and Price, CF and , },
title = {A Randomized Controlled Trial of OPT-302, a VEGF-C/D Inhibitor for Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {130},
number = {6},
pages = {588-597},
doi = {10.1016/j.ophtha.2023.02.001},
pmid = {36754174},
issn = {1549-4713},
mesh = {Humans ; *Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor C/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects ; Vascular Endothelial Growth Factor A ; Angiogenesis Inhibitors ; *Wet Macular Degeneration/diagnosis/drug therapy/chemically induced ; Intravitreal Injections ; Treatment Outcome ; },
abstract = {PURPOSE: Neovascular (wet) age-related macular degeneration (nAMD) is driven by VEGFs A, C, and D, which promote angiogenesis and vascular permeability. Intravitreal injections of anti-VEGF-A drugs are the standard of care, but these do not inhibit VEGF-C and D, which may explain why many patients fail to respond fully. This trial aimed to test the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti-VEGF-A inhibitor ranibizumab.<br><br>DESIGN: Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial.<br><br>PARTICIPANTS: Participants with treatment-naive nAMD were enrolled from 109 sites across Europe, Israel, and the United States.<br><br>METHODS: Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab.<br><br>MAIN OUTCOME MEASURES: The primary outcome was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks. Secondary outcomes (comparing baseline with week 24) were the proportion of participants gaining or losing &#x2265; 15 ETDRS BCVA letters; area under the ETDRS BCVA over time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT.<br><br>RESULTS: Of 366 participants recruited from December 1, 2017, to November 30, 2018, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively. Mean (&#xb1; standard deviation) visual acuity gain in the 2.0 mg OPT-302 group was significantly superior to sham (+14.2 &#xb1; 11.61 vs.&#xa0;+10.8 &#xb1; 11.52 letters; P&#xa0;= 0.01). The 0.5 mg OPT-302 group was not significantly different than the sham group (+9.44 &#xb1; 11.32 letters; P&#xa0;= 0.83). Compared with sham, the secondary BCVA outcomes favored the 2.0 mg OPT-302 group, with structural outcomes favoring both OPT-302 dosage groups. Adverse events (AEs) were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least 1 serious AE. Two unrelated deaths both occurred in the sham arm.<br><br>CONCLUSIONS: Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favorable safety (ClinicalTrials.gov identifier: NCT03345082).<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36753959,
year = {2023},
author = {Martínez-Castillo, R and González-Gallardo, C and Muñoz-Ávila, JI and Font, P and Villalba-González, M and Stoikow, I and Fernández-Choquet de Isla, I and Pugliese, F and Anaya-Alaminos, R and García-Serrano, JL and Hermoso-Fernández, F and Contieri, F and Muñoz-de-Escalona-Rojas, JE and Pérez-Fajardo, L and Blanco-Blanco, M and Jiménez-Gómez, Y and González-Andrades, M},
title = {Treatment of neovascular age-related macular degeneration within 48 h from diagnosis improves long-term functional outcome.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {160},
number = {},
pages = {114368},
doi = {10.1016/j.biopha.2023.114368},
pmid = {36753959},
issn = {1950-6007},
mesh = {Humans ; Infant ; *Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; Vascular Endothelial Growth Factor A ; Retrospective Studies ; Longitudinal Studies ; Intravitreal Injections ; *Macular Degeneration/diagnosis/drug therapy/chemically induced ; Treatment Outcome ; Follow-Up Studies ; },
abstract = {PURPOSE: To evaluate long-term visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients treated with anti-vascular endothelial growth factor (VEGF) agents depending on the time delay from confirmed diagnosis to treatment initiation.<br><br>MATERIALS AND METHODS: Seventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: <&#xa0;48&#xa0;h (group 1); 48&#xa0;h-7 days (group 2); >&#xa0;7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1-2-, 3-4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared.<br><br>RESULTS: Long-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1-2-, 6-, and 12-month follow-up (P&#xa0;<&#xa0;0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P&#xa0;<&#xa0;0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups.<br><br>CONCLUSIONS: An early initial treatment with VEGF inhibitors is critical to achieve the best functional benefits of this therapy in new-onset nAMD patients.},
}
@article {pmid36749597,
year = {2023},
author = {Fenner, BJ and Li, H and Gan, ATL and Song, YS and Tham, YC and Jonas, JB and Wang, YX and Cheng, CY and Wong, TY and Teo, KYC and Tan, ACS and Fan, Q and Cheung, CMG},
title = {Genetic Variability of Complement Factor H Has Ethnicity-Specific Associations With Choroidal Thickness.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {2},
pages = {10},
pmid = {36749597},
issn = {1552-5783},
mesh = {Humans ; *Complement Factor H/genetics ; Ethnicity ; Choroid/pathology ; Retina/pathology ; *Macular Degeneration/genetics ; Polymorphism, Single Nucleotide ; },
abstract = {PURPOSE: To identify genetic alleles associated with differences in choroidal thickness (CT) in a population-based multiethnic Asian cohort.<br><br>METHODS: A population-based multiethnic Asian cohort without retinal pathology was subjected to spectral-domain OCT (SD-OCT) and genotyping of risk alleles in CFH, VIPR2, ARMS2, and CETP. Subfoveal choroidal thickness (SFCT) values were assessed from SD-OCT, and associations with the risk alleles were determined for each cohort.<br><br>RESULTS: A total of 1045 healthy Asian individuals (550 Chinese, 147 Indians, 348 Malays) were prospectively enrolled in the study. Several CFH alleles (rs800292, rs1061170, and rs1329428) were associated with increased SFCT in Indians (+18.7 to +31.7 &#xb5;m; P = 0.001-0.038) and marginally associated with decreased SFCT in Malays (-12.7 to -20.6 &#xb5;m; P = 0.014-0.022). Haplotype analysis of CFH revealed variable associations with SFCT among races, with the H6 haplotype being associated with a 29.08-&#xb5;m reduction in SFCT in the Chinese cohort (P = 0.02) but a 35.2-&#xb5;m increase in SFCT in the Indian cohort (P < 0.001). Finally, subfield analysis of the Chinese cohort identified associations between the CFH risk allele rs1061170 and reduced CT in the nasal and superior sectors (-20.2 to -25.8 &#xb5;m; P = 0.003-0.027).<br><br>CONCLUSIONS: CFH variants are variably associated with CT among Asian ethnic groups. This has broad implications for the pathogenesis of common diseases such as age-related macular degeneration and central serous choroidopathy, the pathogenesis of which is associated with CT.},
}
@article {pmid36749017,
year = {2023},
author = {Zhang, J and Wu, Y and Sharma, B and Gupta, R and Jawla, S and Bullimore, MA},
title = {Epidemiology and Burden of Astigmatism: A Systematic Literature Review.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {100},
number = {3},
pages = {218-231},
pmid = {36749017},
issn = {1538-9235},
mesh = {Adult ; Humans ; *Astigmatism/epidemiology ; Visual Acuity ; Quality of Life ; Vision, Ocular ; *Cataract ; },
abstract = {SIGNIFICANCE: This is the first literature review to report the epidemiology, patient burden, and economic burden of astigmatism in the general adult population. The unmet needs of astigmatism patients with coexisting ocular conditions (cataract, glaucoma, dry eye, presbyopia, or macular degeneration) and risks associated with untreated astigmatism are also reviewed and reported.<br><br>PURPOSE: This study aimed to identify, report, and summarize the published literature on epidemiology, patient burden, and economic burden of astigmatism using a systematic literature review.<br><br>METHODS: MEDLINE, EMBASE, and Cochrane Library databases were searched (January 1996 to May 2021). Search results were limited to the English language. Proceedings (2018 to 2021) from ophthalmology congresses were searched along with gray literature using the Google Scholar platform.<br><br>RESULTS: The literature search yielded 6804 citations, of which 125 met the inclusion criteria (epidemiology, 68; patient burden, 60; economic burden, 6). Astigmatism prevalence in the general population varied from 8 to 62%, with higher rates in individuals 70 years or older. The prevalence of with-the-rule astigmatism was higher in individuals 40 years or younger, whereas rates of against-the-rule and oblique astigmatism increased with age. Astigmatic patients experienced decreased vision quality, increased glare (53 to 77%), haloes (28 to 80%), night-time driving difficulties (66%), falls, and spectacle dependence (45 to 85%). Astigmatic patients performed vision-related tasks slower (1 D, 9% slower; 2 D, 29% slower) and made more errors (1 D, 38% more errors; 2 D, 370% more errors) compared with fully corrected individuals. In cataract patients with astigmatism, the annual mean per-patient productivity loss costs ranged from &#x20ac;55 ($71) to &#x20ac;84 ($108), and mean informal care costs ranged from &#x20ac;30 ($39) to &#x20ac;55 ($71) with a mean of 2.3 to 4.1 hours spent on informal care.<br><br>CONCLUSIONS: Uncorrected astigmatism decreases patients' vision-related quality of life, decreases productivity among working-age adults, and poses an economic burden on patients and their families.},
}
@article {pmid36746120,
year = {2023},
author = {Relton, SD and Chi, GC and Lotery, AJ and West, RM and McKibbin, M and , },
title = {Associations with Non-Persistence with Intra-Vitreal Therapy for Neovascular Age-Related Macular Degeneration at 24 Months.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {2},
pages = {90-98},
doi = {10.1159/000529446},
pmid = {36746120},
issn = {1423-0267},
mesh = {Humans ; Child, Preschool ; Angiogenesis Inhibitors ; State Medicine ; *Macular Degeneration/drug therapy ; *Choroidal Neovascularization/diagnosis/drug therapy ; Eye ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy ; Treatment Outcome ; },
abstract = {AIMS: The aim of the study was to investigate non-persistence with treatment for neovascular age-related macular degeneration (NvAMD) before day 720 (24 months) after initiation, explore associations with baseline characteristics and variation between sites.<br><br>METHODS: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts for NvAMD eyes starting intra-vitreal therapy from 2017 to 2018. Time to non-persistence with treatment, defined as no recorded attendance for either monitoring or treatment for a period &#x2265;6 months, was visualised with a Kaplan-Meier survival plot. Associations with treatment non-persistence were investigated using a Cox proportional hazards model.<br><br>RESULTS: Analysis included 7,970 eyes of 7,112 patients treated at 13 NHS trusts. Censoring deaths and those eyes in which treatment was stopped permanently, the Kaplan-Meier analyses demonstrated survival figures of 77.7% for persistence with treatment to day 360 and 71.8% to day 720. Hazard ratios for non-persistence with treatment were reduced at 10 sites, relative to the reference, with first-treated eye status and with baseline acuity worse than or equal to LogMAR 1.0. Hazard ratios increased with younger age, in the presence of other ocular co-morbidities and with baseline acuity better than or equal to LogMAR 0.5. After an episode of non-persistence, visual acuity decreased by at least 0.1 and 0.3 LogMAR in 39% and 18% of eyes, respectively.<br><br>CONCLUSIONS: Non-persistence with treatment was common, especially in the first year of treatment, and was often associated with a decrease in visual acuity. Treatment site, baseline visual acuity, and age were the strongest predictors of treatment non-persistence before day 720. Understanding and addressing reasons for non-persistence are important to ensure that effective but expensive treatments are used cost-effectively and to maintain acuity. Variation in non-persistence between sites, even after adjustment for other variables, suggests that local factors in treatment provision may be particularly important.},
}
@article {pmid36743667,
year = {2022},
author = {Ming, J and Qin, R},
title = {Trends in research related to ophthalmic microperimetry from 1992 to 2022: A bibliometric analysis and knowledge graph study.},
journal = {Frontiers in medicine},
volume = {9},
number = {},
pages = {1024336},
pmid = {36743667},
issn = {2296-858X},
abstract = {BACKGROUND: Microperimetry is a novel technology to assess macular function. The aim of the study was to explore the global research status and trends in microperimetry.<br><br>METHODS: Documents related to microperimetry in ophthalmology from 1992 to 2022 were extracted from the Science Citation Index Expanded (SCI-E) database of the Web of Science Core Collection (WOSCC). Raw data were analyzed using the VOSviewer and CiteSpace software. Bibliometric parameters included annual publication quantity, countries, authors, journals, international cooperation, and keywords.<br><br>RESULTS: A total of 1,217 peer-reviewed documents were retrieved. Annual research output has increased significantly since 2005, especially since 2013. Holz F, Rubin G, and Guymer R contributed most to the number of articles published about microperimetry. Rubin G, Fitzke F, and Holz F, respectively, received the most citations for their study. The countries publishing most were the USA, Italy, and the UK, while the USA, the UK, and Germany received the most citation frequency. Univ Bonn, UCL, and Moorfields Eye Hosp were the top three productive institutions for microperimetry research in the world. The top three journals that publish articles about microperimetry were Retina-The Journal of Retinal and Vitreous Diseases, Investigative Ophthalmology and Visual Science, and the American Journal of Ophthalmology. The top 10 common keywords included microperimetry, optical coherence tomography, eye, retinal sensitivity, macular degeneration, fundus autofluorescence, scanning laser ophthalmoscope, visual acuity, sensitivity, and degeneration. Keywords "optical coherence tomography angiography," "retinitis pigmentosa," and "internal limiting membrane" burst in the last 3 years.<br><br>CONCLUSION: The bibliometric and knowledge graph analysis of research status and trends in microperimetry provided global researchers with valuable information to propose future cooperation and track cutting-edge progress.},
}
@article {pmid36741078,
year = {2023},
author = {Khan, H and Aziz, AA and Sulahria, H and Khan, H and Ahmed, A and Choudhry, N and Narayanan, R and Danzig, C and Khanani, AM},
title = {Emerging Treatment Options for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {321-327},
pmid = {36741078},
issn = {1177-5467},
abstract = {Age-related macular degeneration (AMD) is characterized as a chronic, multifactorial disease and is the leading cause of irreversible blindness. Advanced AMD is classified as neovascular (wet) AMD and non-neovascular (dry) AMD. Dry AMD can progress to a more advanced form that manifests as geographic atrophy (GA), which significantly threatens vision, leading to progressive and irreversible loss of visual function. There are currently no approved therapeutics commercially available for GA patients. However, data from various clinical trials have demonstrated favorable results with significant reduction in GA lesion growth. This review furthers the understanding of the pathophysiology of GA, as well as current clinical trial data on investigational therapeutics.},
}
@article {pmid36738972,
year = {2023},
author = {Li, W and Chen, L and Gu, Z and Chen, Z and Li, H and Cheng, Z and Li, H and Zou, L},
title = {Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD).},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {355},
number = {},
pages = {358-370},
doi = {10.1016/j.jconrel.2023.01.080},
pmid = {36738972},
issn = {1873-4995},
mesh = {Mice ; Animals ; Quercetin/therapeutic use ; Endothelial Cells/metabolism ; *Macular Degeneration/drug therapy/metabolism ; *Choroidal Neovascularization/drug therapy ; *Nanoparticles/chemistry ; Peptides/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; *MicroRNAs/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), which leads to severe vision loss in middle-aged and elderly patients. Current treatments for CNV show weak, transient efficacy, and they can cause several adverse effects. A potential new treatment is to use microRNA-150 (mR150), which regulates physiological and pathological angiogenesis by modulating the expression of CXCR4 at the post-transcriptional level. Here, we developed solid lipid nanoparticles that we modified with an Asp-Gly-Arg peptide to target endothelial cells during abnormal angiogenesis, then we co-loaded them with mR150 and the anti-angiogenic drug quercetin. The resulting nanoparticles had an average size around 200 nm and showed strong ability to target the fundus and inhibit CNV for up to two weeks in a mouse model without causing retinal toxicity. They significantly enhanced the uptake of mR150 in vitro compared to free mR150 or nanoparticles without peptide. Our study suggests that co-administration of mR150 and quercetin has potential for treating age-related macular degeneration and that nanoparticles modified with Asp-Gly-Arg peptide are an effective platform for the co-delivery of small-molecule and nucleic acid drugs via intravitreal injection.},
}
@article {pmid36736896,
year = {2023},
author = {Sacconi, R and Sarraf, D and Sadda, SR and Freund, KB and Servillo, A and Fogel Levin, MM and Costanzo, E and Corradetti, G and Cabral, D and Zur, D and Trivizki, O and Parravano, M and Bandello, F and Loewenstein, A and Querques, G},
title = {Nascent Geographic Atrophy as a Predictor of Type 3 Macular Neovascularization Development.},
journal = {Ophthalmology. Retina},
volume = {7},
number = {7},
pages = {586-592},
doi = {10.1016/j.oret.2023.01.019},
pmid = {36736896},
issn = {2468-6530},
mesh = {Humans ; Aged ; Aged, 80 and over ; *Geographic Atrophy/diagnosis ; Retrospective Studies ; Longitudinal Studies ; Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis ; *Choroidal Neovascularization/diagnosis/epidemiology/drug therapy ; Fundus Oculi ; },
abstract = {PURPOSE: To investigate the association of nascent geographic atrophy (GA) preceding the development of exudative type 3 macular neovascularization (MNV) in patients with age-related macular degeneration (AMD).<br><br>DESIGN: Retrospective longitudinal study.<br><br>PARTICIPANTS: Patients with AMD diagnosed with treatment-naive exudative type 3 MNV in 1 or both eyes were evaluated. Inclusion criteria included serial tracked structural OCT examinations for &#x2265; 2 years before the detection of exudative type 3 MNV.<br><br>METHODS: Clinical characteristics and retinal imaging, including structural OCT at baseline and at each follow-up examination, were analyzed. Eyes showing the presence of nascent GA during the follow-up were selected for analysis of prevalence, and clinical characteristics at the site of subsequent type 3 MNV development.<br><br>MAIN OUTCOME MEASURES: Description of the prevalence and clinical characteristics of nascent GA at the site of subsequent type 3 MNV development.<br><br>RESULTS: Overall, 97 eyes affected by type 3 MNV meeting inclusion criteria were analyzed. Of 97 eyes (71&#xa0;patients), 22 eyes of 21 patients (mean age 82 &#xb1; 9 years) showed nascent GA preceding exudative type 3&#xa0;MNV. The observed prevalence of nascent GA preceding exudative type 3 MNV was 22.7% (95% confidence interval, 14.4%-31.0%). Exudative type 3 MNV developed a mean of 9 &#xb1; 6 months after detection of nascent GA. The presence of reticular pseudodrusen in the study eye did not significantly influence the timing of exudative type 3 MNV development after the observation of nascent GA (P > 0.1 in all analyses). Reduced best-corrected visual acuity was recorded at the exudative type 3 stage in comparison with the nascent GA stage (P&#xa0;= 0.003).<br><br>CONCLUSIONS: As nascent GA may precede the development of exudative type 3 MNV, the detection of nascent GA in eyes with AMD may warrant closer surveillance to identify early exudative type 3 MNV warranting treatment.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36736867,
year = {2023},
author = {Jia, X and Sun, Y and Wang, T and Zhong, L and Deng, J and Zhu, X},
title = {Mechanism of circular RNA-mediated regulation of L-DOPA to improve wet age-related macular degeneration.},
journal = {Gene},
volume = {861},
number = {},
pages = {147247},
doi = {10.1016/j.gene.2023.147247},
pmid = {36736867},
issn = {1879-0038},
mesh = {Humans ; RNA, Circular/genetics ; Levodopa/genetics ; In Situ Hybridization, Fluorescence ; Vascular Endothelial Growth Factor A/genetics ; *Macular Degeneration ; *MicroRNAs/genetics ; Apoptosis/genetics ; Cell Proliferation/genetics ; },
abstract = {This study aimed to investigate the effect and mechanism of levodopa (L-DOPA) in the treatment of age-related macular degeneration (AMD). A wet AMD cell model was created via CoCl2 treatment of ARPE-19 cells. The cytoprotective effects of L-DOPA in the model were determined using CCK-8, flow cytometry, TUNEL, qPCR, and ELISA assays. Subsequently, circRNA sequencing and bioinformatics analysis were used to screen differentially expressed circRNAs, which were overexpressed in ARPE-19 cells, to explore their role in wet AMD. The findings revealed that 200 μM CoCl2 treatment inhibited the cell viability and the production of tyrosinase, melanin, and pigment epithelium-derived growth factor but promoted apoptosis and the expression of vascular endothelial growth factor in ARPE-19 cells. Moreover, 20 μM L-DOPA exerted the best therapeutic effect on the model. qPCR showed that Hsa_circ_0018401 (circ-SGMS1) was significantly differentially expressed in each experimental group, which was consistent with the sequencing results. The overexpression of circ-SGMS1 in ARPE-19 cells reversed the effects of CoCl2. Fluorescence in situ hybridization showed that circ-SGMS1 was expressed more in the nucleus than in the cytoplasm. qPCR assays indicated that circ-SGMS1 overexpression did not have a significant effect on the expressions of VEGFA and KDR but significantly reduced the expressions of HIF-1a and THBS1. Circ-SGMS1 is of immense significance in the AMD treatment mechanism of L-DOPA. Overexpression of circ-SGMS1 may alleviate wet AMD by inhibiting HIF-1a and THBS1 expression.},
}
@article {pmid36735070,
year = {2023},
author = {Hama, Y and Miyata, M and Ooto, S and Tamura, H and Ueda-Arakawa, N and Muraoka, Y and Miyake, M and Takahashi, A and Wakazono, T and Uji, A and Yamashiro, K and Tsujikawa, A},
title = {Seven-year outcome after 1-year fixed regimen of intravitreal aflibercept injections followed by pro re nata treatment for neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {7},
pages = {1871-1881},
pmid = {36735070},
issn = {1435-702X},
support = {21K09716//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; Ranibizumab ; Angiogenesis Inhibitors ; Retrospective Studies ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins/therapeutic use ; *Macular Degeneration/drug therapy ; *Retinal Detachment/diagnosis ; Intravitreal Injections ; *Retinal Diseases/drug therapy ; Atrophy/drug therapy ; Treatment Outcome ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: The study aims to investigate the 7-year best-corrected visual acuity (BCVA) course after 1-year fixed regimen of intravitreal aflibercept injection (IVA) for neovascular age-related macular degeneration (nAMD) and to identify factors affecting this BCVA.<br><br>METHODS: This longitudinal, observational study included 63 treatment-na&#xef;ve eyes (61 patients) with nAMD, treated with 1-year fixed regimen of IVA-3 monthly injections and 4 subsequent bimonthly injections-essentially followed by PRN regimen of IVA but sometimes followed by agent switching, photodynamic therapy (PDT), or vitrectomy, as needed. We assessed BCVA changes over a 7-year period. Morphologically, we assessed central retinal thickness (CRT), central choroidal thickness (CCT), subfoveal pigment epithelial detachment (PED) height, vitreomacular traction/adhesion (VMT/VMA), epiretinal membrane (ERM), and macular atrophy involving the fovea.<br><br>RESULTS: Logarithm of the minimum angle of resolution (logMAR) BCVA changed from 0.20&#x2009;&#xb1;&#x2009;0.24 to 0.29&#x2009;&#xb1;&#x2009;0.45 over 7&#xa0;years. BCVA improved significantly after years 1 and 2 (P&#x2009;=&#x2009;0.002 and 0.001, respectively) and then slowly decreased. BCVA after years 3-7 did not significantly differ from baseline. CRT and CCT decreased significantly during follow-up, while PED height did not. VMT/VMA decreased significantly, whereas ERM and macular atrophy increased significantly. Seven-year and baseline BCVA positively correlated (P&#x2009;=&#x2009;0.007, &#x3b2;&#x2009;=&#x2009;0.35).<br><br>CONCLUSIONS: BCVA was maintained for 7&#xa0;years in nAMD eyes after 1-year fixed regimen of IVA, essentially followed by PRN regimen, but sometimes followed by agent switching, PDT, or vitrectomy, without severe drug-induced complications. Thus, early diagnosis and treatment of nAMD are essential for maintaining good long-term BCVA, even in eyes with relatively poor baseline vision.},
}
@article {pmid36734705,
year = {2023},
author = {Ay, IE and Kose, F},
title = {Ocular health screening among care-center residents with disabilities: a smartphone adaptive fundus camera cross-sectional study.},
journal = {European review for medical and pharmacological sciences},
volume = {27},
number = {2},
pages = {620-627},
doi = {10.26355/eurrev_202301_31063},
pmid = {36734705},
issn = {2284-0729},
mesh = {Humans ; Adult ; Middle Aged ; Aged ; Cross-Sectional Studies ; Smartphone ; Eye ; *Dry Eye Syndromes/diagnosis ; *Persons with Disabilities ; },
abstract = {OBJECTIVE: The aim of this study was to evaluate the ocular health of care-center residents with disabilities who have difficulty accessing health care using a novel smartphone-adapted fundus camera device, and to compare the results to age- and gender-matched health subjects.<br><br>PATIENTS AND METHODS: In this study, 47 care-center residents with disabilities were investigated between October 1, 2021, and December 31, 2021. A control group was made up of healthy volunteers. All participants underwent a comprehensive ocular exam, which included measuring visual acuity and assessing dry eye with Schirmer and tear break-up time tests. The posterior segment was examined using a smartphone-adapted fundus camera. The data gathered was compared with statistical significance between the two groups.<br><br>RESULTS: The mean ages of disabled and healthy participants were 59.7&#xb1;15.2 and 56.6&#xb1;15.0 years, respectively (p=0.305). While 11.1% of the 36 visually impaired participants were legally blind, the percentage among healthy subjects was only 3.7% (p=0.168). In comparison to healthy participants, disabled people had statistically significantly higher rates of dry eye (27.7%), senile macular degeneration (23.4%), and cataracts (29.8%) (p<0.05).<br><br>CONCLUSIONS: Screening for ocular health with a novel smartphone-adapted fundus camera revealed significantly higher rates of various ocular diseases in care center disabled residents. Given technological progress, remote control method-assisted ocular exams appear to be potentially feasible and clinically beneficial. This could allow trained allied health personnel to perform ocular health screenings without the need to transport a disabled person to the hospital. Thus, diagnosis and follow-up of various chronic ocular diseases may be properly organized.},
}
@article {pmid36732855,
year = {2023},
author = {White, KM and Livnat, I and Frambach, CR and Doan, J and Mehta, UV and Yuh, C and Palma, AM and Jameson, KA and Kenney, MC and Mehta, MC and Boisvert, CJ and Crow, WR and Browne, AW},
title = {Quantitative cone contrast threshold testing in patients with differing pathophysiological mechanisms causing retinal diseases.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {9},
pmid = {36732855},
issn = {2056-9920},
abstract = {BACKGROUND: Cone contrast threshold testing (CCT) provides quantitative measurements of color and contrast function to reveal changes in vision quality that are not standard endpoints in clinical trials. We utilize CCT to measure visual function in patients with multiple sclerosis (MS), age-related macular degeneration (AMD), epiretinal membrane (ERM), and retinal vein occlusion (RVO).<br><br>METHODS: Retrospective data was gathered from 237 patients of the Gavin Herbert Eye Institute. Subjects included 17 patients with MS, 45 patients with AMD, 41 patients with ERM, 11 patients with RVO, and 123 healthy controls. Patients underwent the primary measurement outcome, CCT testing, as well as Sloan visual acuity test and spectral domain optical coherence tomography during normal care.<br><br>RESULTS: Color and contrast deficits were present in MS patients regardless of history of optic neuritis. AMD with intermediate or worse disease demonstrated reduced CCT scores. All 3 stages of ERM demonstrated cone contrast deficits. Despite restoration of visual acuity, RVO-affected eyes demonstrated poorer CCT performance than unaffected fellow eyes.<br><br>CONCLUSIONS: CCT demonstrates color and contrast deficits for multiple retinal diseases with differing pathophysiology. Further prospective studies of CCT in other disease states and with larger samples sizes is warranted.},
}
@article {pmid36731638,
year = {2023},
author = {Grimes, KR and Aloney, A and Skondra, D and Chhablani, J},
title = {Effects of systemic drugs on the development and progression of age-related macular degeneration.},
journal = {Survey of ophthalmology},
volume = {68},
number = {3},
pages = {332-346},
doi = {10.1016/j.survophthal.2023.01.007},
pmid = {36731638},
issn = {1879-3304},
mesh = {Humans ; Aged ; *Wet Macular Degeneration/drug therapy ; Aging ; Inflammation ; Anti-Inflammatory Agents, Non-Steroidal ; Life Style ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of severe loss of central vision among people over 50. The pathophysiology of the disease is multifactorial and can be attributed to genetics, aging, inflammation, environmental factors, and lifestyle factors including smoking, diet, obesity, and alcohol consumption. While there is no treatment for dry AMD, the current standard treatment for wet AMD is an intraocular injection of anti-vascular endothelial growth factor-an effective, yet expensive, therapy that requires ongoing treatment. As the aging population continues to grow, and AMD diagnoses continue to rise, new treatments should be explored to reduce vision complications and decrease treatment burdens. Many systemic conditions have progressive pathological changes that may affect AMD, particularly those affecting systemic vasculature like diabetes and cardiovascular status. Consequently, systemic drugs used to treat coexistent systemic diseases may influence some of the pathogenic mechanisms of AMD and lead its progression or delay. In this review we explore the current literature to summarize the findings of the reported effects of antihypertensive, immunosuppressants, cholesterol lowering agents, nonsteroidal anti-inflammatory drugs, dopamine precursors, hypoglycemic agents, and anticoagulants on AMD.},
}
@article {pmid36731070,
year = {2024},
author = {Romano, F and Cozzi, E and Boon, CJF and Staurenghi, G and Salvetti, AP},
title = {MULTIMODAL RETINAL IMAGING REVEALS NEW PATHOGENIC INSIGHTS IN CENTRAL AREOLAR CHOROIDAL DYSTROPHY: A CASE SERIES.},
journal = {Retinal cases &amp; brief reports},
volume = {18},
number = {1},
pages = {32-38},
doi = {10.1097/ICB.0000000000001325},
pmid = {36731070},
issn = {1937-1578},
mesh = {Female ; Humans ; Young Adult ; Adult ; Retina ; *Choroid Diseases/diagnosis/pathology ; Retinal Pigment Epithelium/pathology ; *Macular Degeneration/pathology ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; },
abstract = {PURPOSE: To describe novel imaging findings in a family affected by central areolar choroidal dystrophy.<br><br>METHODS: Case series with multimodal retinal imaging assessment.<br><br>RESULTS: A 19-year-old asymptomatic woman was referred for bilateral macular defects of the retinal pigment epithelium. Blue-light autofluorescence of her right eye revealed a speckled pattern in the macular area with a ring of decreased autofluorescence using near-infrared autofluorescence. Multimodal assessment of her left eye disclosed a single parafoveal spot of decreased pigmentation that was clearly visible as hyperautofluorescent using blue-light autofluorescence and as hypoautofluorescent using near-infrared autofluorescence. Optical coherence tomography angiography revealed several tiny areas of flow voids in correspondence of the retinal pigment epithelium alterations of both eyes. Three family members were recently diagnosed with presumed age-related macular degeneration and demonstrated well-demarcated areas of retinal pigment epithelium atrophy surrounded by yellowish deposits and a hypopigmented halo. Next-generation genetic analysis for inherited macular dystrophies was performed on the index case and the affected family members and revealed a p.Arg172Gln missense mutation in PRPH2 gene, leading to the diagnosis of central areolar choroidal dystrophy.<br><br>CONCLUSION: Multimodal imaging can reveal new pathogenic insights in central areolar choroidal dystrophy. Of notice, near-infrared autofluorescence and optical coherence tomography angiography are able to detect retinal pigment epithelium hypopigmentation and choriocapillaris rarefaction, respectively, since the earliest stages of the disease.},
}
@article {pmid36730570,
year = {2023},
author = {Nakano, Y and Takeuchi, J and Horiguchi, E and Ota, H and Taki, Y and Ito, Y and Terasaki, H and Nishiguchi, KM and Kataoka, K},
title = {LONG-TERM MORPHOLOGIC CHANGES IN MACULAR NEOVASCULARIZATION UNDER AFLIBERCEPT TREATMENT WITH A TREAT-AND-EXTEND REGIMEN.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {3},
pages = {412-419},
doi = {10.1097/IAE.0000000000003676},
pmid = {36730570},
issn = {1539-2864},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Fluorescein Angiography ; Intravitreal Injections ; *Macular Degeneration/diagnosis ; Neovascularization, Pathologic/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Retrospective Studies ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: To examine the morphologic changes in macular neovascularization (MNV) secondary to age-related macular degeneration after 2 years of aflibercept treatment under a treat-and-extend (T&amp;E) regimen.<br><br>METHODS: This retrospective study analyzed the medical records for 26 eyes of 25 patients diagnosed with treatment-naive neovascular age-related macular degeneration and treated with aflibercept under a treat-and-extend regimen for 2 years. The areas of the MNV and vascular structures were assessed using swept-source optical coherence tomography angiography at baseline and after 2 years of treatment.<br><br>RESULTS: The mean MNV area increased significantly from 0.65 &#xb1; 0.42 mm 2 at baseline to 0.78 &#xb1; 0.45 mm 2 at 2 years. At 2 years, the mean change in the MNV area from baseline was 22% (interquartile range: 4%-60%). The baseline MNV area was negatively correlated with the change ratio of the MNV areas at 2 years and baseline (R = -0.68, P < 0.001). Nine of the 26 eyes (34.6%) showed newly formed mature vessels, and 7 eyes (26.9%) showed prominently developing preexisting mature vessels.<br><br>CONCLUSION: Macular neovascularization expanded and showed vascular maturation under aflibercept treatment with a treat-and-extend regimen. The smaller the MNV at baseline, the greater is its expansion in 2 years.},
}
@article {pmid36730109,
year = {2024},
author = {Fukui, T and Ishikawa, K and Shiose, S and Kano, K and Mori, K and Notomi, S and Sonoda, KH},
title = {SPATIAL PATTERN OF RETINAL PIGMENT EPITHELIUM TEAR DEVELOPMENT AND PROGRESSION AFTER ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retinal cases &amp; brief reports},
volume = {18},
number = {3},
pages = {371-377},
doi = {10.1097/ICB.0000000000001386},
pmid = {36730109},
issn = {1937-1578},
mesh = {Humans ; Retrospective Studies ; Male ; *Angiogenesis Inhibitors/adverse effects ; *Retinal Perforations/chemically induced/diagnosis ; Female ; *Retinal Pigment Epithelium/pathology/drug effects ; Aged ; *Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged, 80 and over ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Disease Progression ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; *Visual Acuity ; Ranibizumab/adverse effects/administration &amp; dosage ; Bevacizumab/adverse effects ; Fundus Oculi ; Follow-Up Studies ; Choroidal Neovascularization/drug therapy ; },
abstract = {PURPOSE: The aim of this study was to demonstrate the spatial pattern of retinal pigment epithelium (RPE) tear development and progression after antivascular endothelial growth factor therapy for neovascular age-related macular degeneration.<br><br>METHODS: We retrospectively reviewed six eyes with neovascular age-related macular degeneration that showed RPE tears after administration of intravitreal antivascular endothelial growth factor agents and were followed up for 12 months. The patterns of RPE tear development and progression were evaluated by analyzing positional relationships among the locations of the choroidal neovascularization membrane and pigment epithelial detachment (PED) area at baseline and the tear area using spectral-domain optical coherence tomography, color photography, fluorescein angiography, and fundus autofluorescence images.<br><br>RESULTS: Pretear OCT images revealed fibrovascular PED in all eyes, one of which showed complications of hemorrhagic PED after treatment. In five eyes, RPE tears developed at the PED edge located on the opposite side of the choroidal neovascularization membrane. In the eye showing hemorrhagic PED, the RPE tear developed along the wide area of the PED edge. The torn RPE monolayer contracted toward the side of the choroidal neovascularization membrane in all eyes, and RPE loss involved the fovea in five eyes that showed significantly worse visual acuity (VA) after 12 months in comparison with the baseline value before the tear (logMAR VA; 0.3 vs. 1.29; P < 0.02).<br><br>CONCLUSION: The location of choroidal neovascularization membrane in PED determines the spatial pattern of RPE tear development and progression and helps to predict the visual outcome after RPE tears.},
}
@article {pmid36729623,
year = {2023},
author = {Montolío-Marzo, S and Gallego-Pinazo, R and Palacios-Pozo, E and Dolz-Marco, R},
title = {ADVANTAGES OF OPTICAL COHERENCE TOMOGRAPHY AS A HIGH DYNAMIC RANGE IMAGING MODALITY IN SUBRETINAL HYPERREFLECTIVE MATERIAL.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {4},
pages = {641-648},
doi = {10.1097/IAE.0000000000003705},
pmid = {36729623},
issn = {1539-2864},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Fluorescein Angiography ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; Subretinal Fluid/diagnostic imaging ; },
abstract = {PURPOSE: To describe the utility of high dynamic range optical coherence tomography imaging to study subretinal hyperreflective material (SHRM) in patients with age-related macular degeneration.<br><br>METHODS: Clinical information including visual acuity and optical coherence tomography images (Heidelberg Engineering GmbH, Heidelberg, Germany) of patients undergoing antiangiogenic treatment for neovascular age-related macular degeneration and showing SHRM at baseline were retrospectively reviewed. Contrast between strong signal structures (high dynamic range image) reclassifying SHRM as hyperreflective (HyperR), isoreflective, and hyporeflective was increased. The patients at baseline, 3, 6, and 12-months follow-up were evaluated.<br><br>RESULTS: Forty-four eyes were classified as 15 HyperR (34.1%), 21 as isoreflective (47.7%), and eight as hyporeflective (18.2%). During follow-up, hyporeflective SHRM disappeared in all cases, isoreflective SHRM faded in 16 cases (76.2%); HyperR SHRM remained in all cases. Hyporreflective SHRM showed a greater visual acuity improvement than HyperR SHRM group (P = 0.033). After 12-month follow-up, only the hyporeflective and isoreflective groups significantly reduced the presence of fluid in 37.5% (P = 0.250) and 46.62% (P = 0.006) of the patients, respectively; outer retinal layers were disrupted more frequently in the presence of HyperR SHRM (ellipsoid zone, P = 0.16; external limiting membrane, P = 0.007).<br><br>CONCLUSION: Contrast-enhanced optical coherence tomography images enabled us to classify SHRM according to its reflectivity, showing groups with different disappearance rates, visual acuity improvement, and outer retinal layer disruption. This easy-to-access tool may be helpful as a prognostic factor in neovascular age-related macular degeneration cases.},
}
@article {pmid36729565,
year = {2023},
author = {Lee, H and Kim, S and Kim, MA and Chung, H and Kim, HC},
title = {QUANTIFIED ANASTOMOTIC AREAS OF NEOVASCULARIZATION AS FACTORS ASSOCIATED WITH FREQUENT RECURRENCE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {5},
pages = {747-754},
doi = {10.1097/IAE.0000000000003703},
pmid = {36729565},
issn = {1539-2864},
mesh = {Humans ; Infant ; Angiogenesis Inhibitors/therapeutic use ; Fluorescein Angiography/methods ; *Retinal Neovascularization/drug therapy ; *Choroidal Neovascularization/diagnosis/drug therapy/complications ; Tomography, Optical Coherence/methods ; *Macular Degeneration/complications ; Intravitreal Injections ; *Wet Macular Degeneration/diagnosis/drug therapy/complications ; Retrospective Studies ; },
abstract = {PURPOSE: To investigate the quantitative characteristics of anastomoses of macular neovascularization (MNV) in neovascular age-related macular degeneration using optical coherence tomography angiography according to the frequency of intravitreal injections.<br><br>METHODS: Eighty-six eyes of 86 patients treated for neovascular age-related macular degeneration were classified into two groups based on the number of intravitreal injections administered over 12 months: stable (<3) and unstable (&#x2265;3). Anastomotic areas were defined as areas surrounded by neighboring vessels in the MNV; their total number, mean area, maximal and minimal diameters (i.e., maximal and minimum Feret diameters), and ratio (Feret aspect ratio) were analyzed in the inner and outer areas of the MNV.<br><br>RESULTS: Forty-four and 42 eyes were classified into the stable and unstable groups, respectively. The eyes in the unstable group had larger anastomotic areas with longer minimum Feret diameters and longer perimeters in the outer MNV. In the logistic regression analysis, instability was associated with a larger anastomotic area and a longer minimum Feret diameter in the outer MNV. Multivariate analysis revealed that a longer minimum Feret diameter in the outer MNV was the most significant factor (P = 0.03).<br><br>CONCLUSION: The quantitative characteristics of the anastomotic areas in the MNV might indicate the need for intravitreal injections in patients with neovascular age-related macular degeneration.},
}
@article {pmid36729084,
year = {2023},
author = {Adrean, SD and Chaili, S and Hill, L and Amador-Patarroyo, MJ},
title = {PATTERNS OF SUBRETINAL AND/OR INTRARETINAL FLUID RECURRENCE IN PATIENTS WHO RECEIVED AS-NEEDED RANIBIZUMAB THERAPY IN THE HARBOR TRIAL.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {4},
pages = {624-631},
pmid = {36729084},
issn = {1539-2864},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Ranibizumab/therapeutic use ; Subretinal Fluid ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/diagnosis/drug therapy ; World Health Organization ; },
abstract = {PURPOSE: To evaluate subretinal fluid (SRF) and/or intraretinal fluid recurrence in patients with neovascular age-related macular degeneration who received as-needed (PRN) ranibizumab in a HARBOR (NCT00891735) post hoc analysis.<br><br>METHODS: Analyses included patients with SRF and/or intraretinal fluid at baseline and fluid recurrence after a &#x2265;3-month absence (N = 222). Baseline fluid location(s) were compared with location of recurrence after a &#x2265;3-month absence.<br><br>RESULTS: At baseline, fluid was equally distributed across all locations. On recurrence, the location was most frequently central (69%). Eyes with central fluid at baseline typically had recurrence in the same location (72% vs. 47%-53% with fluid in other locations). The type of recurrent fluid was typically the same as at baseline (SRF, 64%; intraretinal fluid, 75%). Overall, 37% (39/105) of eyes exhibited fluid recurrence in a new location, most frequently central (53%). There was a significant gain in best-corrected visual acuity (mean [95% confidence interval], +2.2 [0.4-4.0] letters) between the months of SRF resolution and recurrence.<br><br>CONCLUSION: Although the location of SRF and/or intraretinal fluid was equally distributed at baseline, recurrent fluid was typically centrally located. The authors identified a subgroup of eyes exhibiting fluid recurrence in a different location than at baseline, potentially indicating new choroidal neovascularization.},
}
@article {pmid36728874,
year = {2023},
author = {Schneider, EW and Thomas, MK and Recchia, FM and Reichstein, DA and Awh, CC},
title = {SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {5},
pages = {739-746},
doi = {10.1097/IAE.0000000000003729},
pmid = {36728874},
issn = {1539-2864},
mesh = {Humans ; Angiogenesis Inhibitors ; Prospective Studies ; Treatment Outcome ; Visual Acuity ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Recombinant Fusion Proteins/therapeutic use ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To assess the safety and efficacy of biweekly (every 2 weeks) intravitreal aflibercept injections (IAI) 2 mg in eyes with refractory neovascular age-related macular degeneration (NVAMD).<br><br>METHODS: A prospective, single-arm, interventional study was conducted. Eyes with refractory NVAMD received six biweekly IAIs through week 12, followed by a 4-week treatment pause until week 16. Eyes with residual subretinal fluid (SRF) at week 16 were randomized 1:1 to either four additional biweekly IAIs or to 4-week (q4W) IAI dosing through week 24. All eyes were subsequently treated q4W through week 52.<br><br>RESULTS: Enrolled eyes (n = 22) had persistent SRF despite a mean of 11.8 injections over the prior 12 months. One patient developed endophthalmitis at week 12. There were no additional drug/procedure-related adverse events. Best-corrected visual acuity (BCVA) improved significantly from baseline to week 14 (2.52 letters, P < 0.001). The mean central subfield thickness (CST) was also significantly improved at week 14 (-31.9 &#xb5; m, P < 0.001) with eight of 22 eyes achieving complete SRF resolution. Only two of eight eyes remained free of SRF at week 16, with a corresponding increase in mean CST of 26.7 &#xb5; m compared with week 14. By week 52, improvements in BCVA and CST were lost.<br><br>CONCLUSION: In patients with refractory NVAMD-related SRF, sustained biweekly IAIs resulted in significant functional and anatomical improvements during biweekly dosing. These gains, however, were lost on return to monthly dosing. These findings suggest that efforts to reduce refractory SRF in NVAMD with biweekly dosing may provide added benefit compared with standard of care treatment if biweekly dosing is sustained.},
}
@article {pmid36728560,
year = {2023},
author = {Bianco, L and Antropoli, A and Arrigo, A and Berni, A and La Franca, L and Saladino, A and Bandello, F and Battaglia Parodi, M},
title = {FUNDUS AUTOFLUORESCENCE IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN AND DIFFUSE TRICKLING GEOGRAPHIC ATROPHY.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {5},
pages = {755-761},
doi = {10.1097/IAE.0000000000003733},
pmid = {36728560},
issn = {1539-2864},
mesh = {Humans ; *Geographic Atrophy/diagnosis/complications ; Disease Progression ; *Macular Degeneration/complications/diagnosis ; Fundus Oculi ; Atrophy ; Fluorescein Angiography ; },
abstract = {PURPOSE: To establish whether extensive macular atrophy with pseudodrusen (EMAP) can be distinguished from the diffuse-trickling phenotype of geographic atrophy (DTGA) secondary to age-related macular degeneration on the basis of its features on blue-light autofluorescence.<br><br>METHODS: The authors reviewed our prospectively maintained database to enroll patients with a diagnosis of EMAP, DTGA, and non-DTGA with a minimum follow-up of 1 year. Atrophic areas and growth rates were measured on blue-light autofluorescence images, using the Heidelberg Region Finder tool. Circularity and roundness were chosen as atrophy shape descriptors, extracted using ImageJ, and compared between disease groups.<br><br>RESULTS: A total of 28 EMAP, 27 DTGA, and 30 non-DTGA eyes were included in the analysis. The median follow-up time was around 3.5 years. Extensive macular atrophy with pseudodrusen was characterized by an irregular and elongated shape (low circularity and low roundness) and associated with a fast atrophy growth rate (3.6 mm 2 /year), compared with non-DTGA. However, these parameters were not significantly different between EMAP and DTGA.<br><br>CONCLUSION: Our study found that EMAP and DTGA cannot be effectively differentiated on fundus autofluorescence. In both diseases, the macular atrophic area has a major vertical axis, fringed borders, and fast progression.},
}
@article {pmid36726309,
year = {2023},
author = {Bek, T and Bech, BH},
title = {Visual acuity and causes of central visual loss in the adult Danish population 2020-2022. Results from the FORSYN study.},
journal = {Acta ophthalmologica},
volume = {101},
number = {5},
pages = {504-513},
doi = {10.1111/aos.15641},
pmid = {36726309},
issn = {1755-3768},
support = {Grant not numbered//Danish Society for the Blind (Dansk Blindesamfund)/ ; //Synoptik-Fonden/ ; },
mesh = {Humans ; Adult ; Aged ; Aged, 80 and over ; *Diabetic Retinopathy ; Quality of Life ; Vision Disorders/epidemiology ; Visual Acuity ; Scotoma ; Denmark/epidemiology ; },
abstract = {PURPOSE: Knowledge of visual health in the population is necessary for designing and implementing measures to handle visual handicap. The purpose of the FORSYN (Forekomst af synshandicap og synshjaelpemidler i Danmark) project was to study visual health in the Danish population 2020-2022 after implementation of the recent advances in the management of choroidal and retinal vascular disease. The present study reports visual acuity and causes of central visual loss from this study.<br><br>METHODS: A population-representative sample of 10&#x2009;350 citizens living within 40 kilometres from Aarhus University Hospital were invited to answer a questionnaire about quality of life related to vision, measurement of visual acuity and a non-mydriatic examination of the eyes. The data were corrected for selection bias on the basis of demographic and socioeconomic factors so that the results could be projected to represent the adult Danish population.<br><br>RESULTS: Population-adjusted visual acuity in ETDRS letters (mean&#x2009;&#xb1;&#x2009;SD) differed significantly (p&#x2009;<&#x2009;0.0001) among the worse eye (84.1&#x2009;&#xb1;&#x2009;0.25), the better eye (88.4&#x2009;&#xb1;&#x2009;0.11) and binocularly (89.2&#x2009;&#xb1;&#x2009;0.15). Social blindness affected 0.22% (95% CI: 0.14%-0.33%) of the population and was in none of the studied persons due to exudative age-related macular degeneration (AMD) or diabetic retinopathy. The most frequent causes of visual loss were atrophic AMD, neuro-ophthalmic disorders and other chorioretinal diseases.<br><br>CONCLUSIONS: Recent advances in the therapy of chorioretinal vascular diseases have been paralleled with a reduction in central vision loss secondary to exudative AMD and diabetic retinopathy in Denmark. The demographic development can be expected to increase the demand for treatments of vision-threatening diseases that mainly affect older persons.},
}
@article {pmid36726178,
year = {2023},
author = {Coney, JM and Zubricky, R and Sinha, SB and Sonbolian, N and Zhou, L and Hull, TP and Lewis, SA and Miller, DG and Novak, MA and Pendergast, SD and Pham, H and Platt, SM and Rao, LJ and Schartman, JP and Singerman, LJ and Donkor, R and Fink, M and McCoy, J and Karcher, H},
title = {Switching to brolucizumab: injection intervals and visual, anatomical and safety outcomes at 12 and 18 months in real-world eyes with neovascular age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {9},
number = {1},
pages = {8},
pmid = {36726178},
issn = {2056-9920},
abstract = {BACKGROUND: The anti-vascular endothelial growth factor (anti-VEGF) injection interval influences treatment burden and compliance in neovascular age-related macular degeneration (nAMD). This real-world study investigates visual acuity (VA), injection-interval extension, central macular thickness (CMT) and safety in nAMD eyes switched to the anti-VEGF agent brolucizumab and followed for up to 18 months.<br><br>METHODS: This retrospective study included patients with nAMD who were switched from other anti-VEGF agents to brolucizumab only. Patient eyes were grouped into three nested cohorts with the overall cohort receiving&#x2009;&#x2265;&#x2009;1 brolucizumab injection, the second receiving&#x2009;&#x2265;&#x2009;3 brolucizumab injections with a follow-up period of&#x2009;&#x2265;&#x2009;12&#xa0;months and the third cohort receiving&#x2009;&#x2265;&#x2009;3 brolucizumab injections with a follow-up period of&#x2009;&#x2265;&#x2009;18&#xa0;months. Study endpoints included changes from baseline at 12 or 18&#xa0;months in VA, injection intervals, and CMT. Sub-group analyses were conducted using baseline injection interval length or baseline VA as qualifiers.<br><br>RESULTS: Overall, 482 eyes received&#x2009;&#x2265;&#x2009;1 brolucizumab injection; 174 eyes received&#x2009;&#x2265;&#x2009;3 brolucizumab injections with&#x2009;&#x2265;&#x2009;12&#xa0;months of follow-up, and 95 eyes received&#x2009;&#x2265;&#x2009;3 brolucizumab injections with&#x2009;&#x2265;&#x2009;18&#xa0;months of follow-up. VA (mean [95% confidence intervals]) remained stable relative to baseline after 12&#xa0;months (-&#xa0;1.1 [-&#xa0;3.7, 1.6] letters; p&#x2009;=&#x2009;0.42) and 18&#xa0;months (0.0 [-&#xa0;3.1, 3.1] letters; p&#x2009;=&#x2009;0.98) of brolucizumab treatment, respectively, and pre-switch injection intervals or baseline VA had no notable effect. Following the switch to brolucizumab, injection intervals were extended from baseline to month 12 by 26.9 (19.7, 34.0) days (p&#x2009;<&#x2009;0.0001), and eyes with pre-switch injection intervals&#x2009;<&#x2009;8&#xa0;weeks were able to have their injection intervals extended by 23.6&#xa0;days longer than eyes with pre-switch injection intervals&#x2009;&#x2265;&#x2009;8&#xa0;weeks. At 18&#xa0;months, injection intervals were extended by 36.3 (25.6, 46.9) days (p&#x2009;<&#x2009;0.0001) compared to baseline. Following switch to brolucizumab, CMT was reduced at both 12 and 18&#xa0;months (12&#xa0;months: -&#xa0;35.2 (-&#xa0;51.7, -&#xa0;18.8) &#xb5;m, p&#x2009;<&#x2009;0.0001; 18&#xa0;months: -&#xa0;38.9 (-&#xa0;54.3, -&#xa0;22.0) &#xb5;m, p&#x2009;<&#x2009;0.0001). Intraocular inflammation-related adverse events were reported in 4.6% of brolucizumab-treated eyes.<br><br>CONCLUSIONS: This real-world study demonstrates that injection intervals may be significantly extended with maintained vision and reduced CMT in nAMD eyes switching to brolucizumab therapy from other anti-VEGFs.},
}
@article {pmid36726055,
year = {2023},
author = {Zhang, W and Roberts, TV and Poulos, CJ and Stanaway, FF},
title = {Prevalence of visual impairment in older people living with dementia and its impact: a scoping review.},
journal = {BMC geriatrics},
volume = {23},
number = {1},
pages = {63},
pmid = {36726055},
issn = {1471-2318},
mesh = {Humans ; Aged ; Prevalence ; *Dementia/diagnosis/epidemiology/psychology ; *Vision, Low/epidemiology ; *Eye Diseases ; Caregivers/psychology ; },
abstract = {BACKGROUND AND OBJECTIVES: Visual impairment (VI) and dementia both increase with age, and it is likely that many older people are living with both conditions. This scoping review aims to investigate the prevalence and types of VI among older people living with dementia, and the impact of VI on older people living with dementia and their caregivers.<br><br>METHODS: This scoping review used Arksey and O'Malley's methodological framework. Studies in any setting involving people living with dementia and some assessment of either VI, eye diseases causing VI or the impact of VI were included.<br><br>RESULTS: Thirty-six studies were included. Thirty-one studies reported the prevalence of VI in older people living with dementia, while ten studies reported on impacts of VI on people living with dementia. Only one study reported on impacts on caregivers. The prevalence of VI or specific eye diseases among older people living with dementia ranged from 0.2 to 74%. The impacts of VI on older people living with dementia included increased use of hospital services, increased disability and dependency, reduced social engagement, negative emotions, increased abnormal behaviours, loss of hobbies, difficulty in using visual aids or memory aids, and greater Neuropsychiatric Inventory symptoms. And the impacts on caregivers included increased conflict and physical exhaustion.<br><br>CONCLUSION: VI is common in older people living with dementia and is associated with negative impacts on those with dementia and their caregivers. However, heterogeneity between studies in terms of setting and method for assessing and defining VI make it difficult to compare findings among studies. Further research is needed, particularly assessing the impact on caregivers.},
}
@article {pmid36725879,
year = {2023},
author = {Antropoli, A and Arrigo, A and Bianco, L and Berni, A and Lamberto, F and Saladino, A and Bandello, F and Battaglia Parodi, M},
title = {Quantitative multimodal imaging of extensive macular atrophy with pseudodrusen and geographic atrophy with diffuse trickling pattern.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {1822},
pmid = {36725879},
issn = {2045-2322},
mesh = {Humans ; *Geographic Atrophy/diagnostic imaging ; Prospective Studies ; Fluorescein Angiography/methods ; Disease Progression ; *Macular Degeneration/diagnostic imaging ; Tomography, Optical Coherence/methods ; Atrophy ; Multimodal Imaging ; Retrospective Studies ; },
abstract = {To compare clinical and imaging characteristics of extensive macular atrophy with pseudodrusen-like appearance (EMAP) versus diffuse-trickling geographic atrophy (DTGA) and non-diffuse-trickling geographic atrophy (nDTGA) phenotypes of age-related macular degeneration. Prospective, observational study performed in the Ophthalmology Department of IRCCS San Raffaele Hospital between January 2015 and January 2021. Patients examination included fundus autofluorescence (FAF) and optical coherence tomography at baseline and follow-up visits. We measured subfoveal choroidal thickness (SCT), Sattler/choroid ratio (SCR), choroidal vascularity index and ellipsoid zone disruption distance on OCT scans. We calculated progression rates and circularity of the atrophic lesions on FAF images. These variables were compared between the three groups and correlations with progression rates and visual acuity were assessed. Sixty-three eyes from 63 patients were included: 18 with EMAP, 18 with DTGA and 27 with nDTGA. Mean follow-up was 3.73 ± 2.12 years. EMAP and DTGA shared a faster progression, lower circularity and SCR, and higher EZ disruption distance than nDTGA, while SCT and CVI were similar between the three groups. Baseline circularity and SCR correlated with progression rates. EMAP and DTGA show similar OCT and FAF characteristics, which differ from nDTGA.},
}
@article {pmid36725098,
year = {2023},
author = {Hogg, HDJ and Brittain, K and Teare, D and Talks, J and Balaskas, K and Keane, P and Maniatopoulos, G},
title = {Safety and efficacy of an artificial intelligence-enabled decision tool for treatment decisions in neovascular age-related macular degeneration and an exploration of clinical pathway integration and implementation: protocol for a multi-methods validation study.},
journal = {BMJ open},
volume = {13},
number = {2},
pages = {e069443},
pmid = {36725098},
issn = {2044-6055},
support = {MC_PC_19005/MRC_/Medical Research Council/United Kingdom ; MR/T019050/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; Critical Pathways ; State Medicine ; Artificial Intelligence ; Retrospective Studies ; *Macular Degeneration/drug therapy ; },
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) management is one of the largest single-disease contributors to hospital outpatient appointments. Partial automation of nAMD treatment decisions could reduce demands on clinician time. Established artificial intelligence (AI)-enabled retinal imaging analysis tools, could be applied to this use-case, but are not yet validated for it. A primary qualitative investigation of stakeholder perceptions of such an AI-enabled decision tool is also absent. This multi-methods study aims to establish the safety and efficacy of an AI-enabled decision tool for nAMD treatment decisions and understand where on the clinical pathway it could sit and what factors are likely to influence its implementation.<br><br>METHODS AND ANALYSIS: Single-centre retrospective imaging and clinical data will be collected from nAMD clinic visits at a National Health Service (NHS) teaching hospital ophthalmology service, including judgements of nAMD disease stability or activity made in real-world consultant-led-care. Dataset size will be set by a power calculation using the first 127 randomly sampled eligible clinic visits. An AI-enabled retinal segmentation tool and a rule-based decision tree will independently analyse imaging data to report nAMD stability or activity for each of these clinic visits. Independently, an external reading centre will receive both clinical and imaging data to generate an enhanced reference standard for each clinic visit. The non-inferiority of the relative negative predictive value of AI-enabled reports on disease activity relative to consultant-led-care judgements will then be tested. In parallel, approximately 40 semi-structured interviews will be conducted with key nAMD service stakeholders, including patients. Transcripts will be coded using a theoretical framework and thematic analysis will follow.<br><br>ETHICS AND DISSEMINATION: NHS Research Ethics Committee and UK Health Research Authority approvals are in place (21/NW/0138). Informed consent is planned for interview participants only. Written and oral dissemination is planned to public, clinical, academic and commercial stakeholders.},
}
@article {pmid36724628,
year = {2023},
author = {Wang, L and Yu, X and Zhang, D and Wen, Y and Zhang, L and Xia, Y and Chen, J and Xie, C and Zhu, H and Tong, J and Shen, Y},
title = {Long-term blue light exposure impairs mitochondrial dynamics in the retina in light-induced retinal degeneration in vivo and in vitro.},
journal = {Journal of photochemistry and photobiology. B, Biology},
volume = {240},
number = {},
pages = {112654},
doi = {10.1016/j.jphotobiol.2023.112654},
pmid = {36724628},
issn = {1873-2682},
mesh = {Mice ; Animals ; *Retinal Degeneration/etiology ; Reactive Oxygen Species/metabolism ; Mitochondrial Dynamics ; Mice, Inbred C57BL ; Retina/metabolism ; Oxidative Stress/radiation effects ; Light ; Retinal Pigment Epithelium ; },
abstract = {Long-term light exposure, especially in the spectrum of blue light, frequently causes excessive oxidative stress in dry age-related macular degeneration (AMD). Here, to gain insight into the underlying mechanism, we focused on mitochondrial dynamics alterations under long-term exposure to blue light in mouse and retinal cells. Six-month-old C57BL/6 mice were exposed to blue light (450 nm, 800 lx) for 2 weeks. The phenotypic changes in the retina were assayed using haematoxylin-eosin staining and transmission electron microscopy. Long-term blue light exposure significantly thinned each retinal layer in mice, induced retinal apoptosis and impaired retinal mitochondria. A retinal pigment epithelial cell line (ARPE-19) was used to verify the phototoxicity of blue light. Flow cytometry, immunofluorescence and MitoSox Red probe experiments confirmed that more total and mitochondria-specific ROS were generated in the blue light group than in the control group. Mito-Tracker Green probe showed fragmented mitochondrial morphology. The western blotting results indicated a significant increase in DRP1, OMA1, and BAX and a decrease in OPA1 and Bcl-2. In conclusion, long-term exposure to blue light damaged the retinas of mice, especially the ONL and RPE cells. There was destruction and dysfunction of mitochondria in RPE cells in vivo and in vitro. Mitochondrial dynamics were disrupted with characteristics of fusion-related obstruction after blue-light irradiation.},
}
@article {pmid36724238,
year = {2023},
author = {Karle, AC and Wrobel, MB and Koepke, S and Gutknecht, M and Gottlieb, S and Christen, B and Rubic-Schneider, T and Pruimboom-Brees, I and Leber, XC and Scharenberg, M and Maciejewski, B and Turner, O and Saravanan, C and Huet, F and Littlewood-Evans, A and Clemens, A and Grosskreutz, CL and Kearns, JD and Mehan, P and Schmouder, RL and Sasseville, V and Brees, D},
title = {Anti-brolucizumab immune response as one prerequisite for rare retinal vasculitis/retinal vascular occlusion adverse events.},
journal = {Science translational medicine},
volume = {15},
number = {681},
pages = {eabq5241},
doi = {10.1126/scitranslmed.abq5241},
pmid = {36724238},
issn = {1946-6242},
mesh = {Animals ; Humans ; Adjuvants, Immunologic ; Angiogenesis Inhibitors ; Inflammation ; Intravitreal Injections ; Macaca fascicularis ; *Retinal Vasculitis ; Vascular Endothelial Growth Factor A ; },
abstract = {In October 2019, Novartis launched brolucizumab, a single-chain variable fragment molecule targeting vascular endothelial growth factor A, for the treatment of neovascular age-related macular degeneration. In 2020, rare cases of retinal vasculitis and/or retinal vascular occlusion (RV/RO) were reported, often during the first few months after treatment initiation, consistent with a possible immunologic pathobiology. This finding was inconsistent with preclinical studies in cynomolgus monkeys that demonstrated no drug-related intraocular inflammation, or RV/RO, despite the presence of preexisting and treatment-emergent antidrug antibodies (ADAs) in some animals. In this study, the immune response against brolucizumab in humans was assessed using samples from clinical trials and clinical practice. In the brolucizumab-naïve population, anti-brolucizumab ADA responses were detected before any treatment, which was supported by the finding that healthy donors can harbor brolucizumab-specific B cells. This suggested prior exposure of the immune system to proteins with structural similarity. Experiments on samples showed that naïve and brolucizumab-treated ADA-positive patients developed a class-switched, high-affinity immune response, with several linear epitopes being recognized by ADAs. Only patients with RV/RO showed a meaningful T cell response upon recall with brolucizumab. Further studies in cynomolgus monkeys preimmunized against brolucizumab with adjuvant followed by intravitreal brolucizumab challenge demonstrated that high ADA titers were required to generate ocular inflammation and vasculitis/vascular thrombosis, comparable to RV/RO in humans. Immunogenicity therefore seems to be a prerequisite to develop RV/RO. However, because only 2.1% of patients with ADA develop RV/RO, additional factors must play a role in the development of RV/RO.},
}
@article {pmid36721668,
year = {2023},
author = {Karimaghaei, C and Ali, A and Safdar, N and Tanwani, A and Schmitz-Brown, M and Banaee, T and El-Annan, J and Gupta, PK},
title = {The Injection Practice Patterns of Retina Specialists in Managing Exudative Age-Related Macular Degeneration: A Retrospective Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {375-383},
pmid = {36721668},
issn = {1177-5467},
abstract = {PURPOSE: To compare the PRN anti-VEGF injection patterns of four retina specialists with respect to the visual and anatomic outcomes in the management of wet age-related macular degeneration (AMD).<br><br>METHODS: Medical records of patients who received bevacizumab, ranibizumab, and aflibercept anti-VEGF injections (years 2010-2020) by four retina specialists were reviewed for frequency, injection intervals, best corrected visual acuity (BCVA), and central macular thickness, center involved (CMT) for statistical analysis. Outcomes measured were change in logMAR BCVA and CMT from the first to last injection visit.<br><br>RESULTS: Out of 137 AMD patients, 172 eyes were injected by four retina specialists in PRN fashion. Although all four specialists started the injection at similar baseline BCVA and CMT (p > 0.1), significant differences in mean injection number (9.0, p = 0.0001), injection intervals (5.06 weeks, p = 0.001), and total length of treatments (53.3 weeks, p = 0.0001) were observed. The mean change in logMAR BCVA between the first and last injection was -0.05, -0.22, 0.07, and 0.06 for the four specialists, respectively (p = 0.031), and the mean change in CMT was -53.3, -41.4, -72.7, and -21.9 &#xb5;m (p = 0.41), respectively.<br><br>CONCLUSION: Despite similar baseline criteria for injections by the retina specialists, different anti-VEGF injection regimens were practiced resulting in variations in BCVA and CMT outcomes. This suggests a need in establishing a universally adoptable injection regimen with possible integration of the confounding factors to reduce burden on both patients and retina specialists.},
}
@article {pmid36720900,
year = {2023},
author = {Muniyandi, A and Martin, M and Sishtla, K and Motolani, A and Sun, M and Jensen, NR and Qi, X and Boulton, ME and Prabhu, L and Lu, T and Corson, TW},
title = {PRMT5 is a therapeutic target in choroidal neovascularization.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {1747},
pmid = {36720900},
issn = {2045-2322},
support = {UL1TR002529/TR/NCATS NIH HHS/United States ; R01EY025641/EY/NEI NIH HHS/United States ; R01 EY025641/EY/NEI NIH HHS/United States ; R01 EY031939/EY/NEI NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; R01 GM120156/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Mice ; Humans ; Vascular Endothelial Growth Factor A/genetics ; Endothelial Cells ; NF-kappa B ; *Choroidal Neovascularization/genetics ; Retina ; *Pancreatic Neoplasms ; Protein-Arginine N-Methyltransferases/genetics ; },
abstract = {Ocular neovascular diseases including neovascular age-related macular degeneration (nvAMD) are widespread causes of blindness. Patients' non-responsiveness to currently used biologics that target vascular endothelial growth factor (VEGF) poses an unmet need for novel therapies. Here, we identify protein arginine methyltransferase 5 (PRMT5) as a novel therapeutic target for nvAMD. PRMT5 is a well-known epigenetic enzyme. We previously showed that PRMT5 methylates and activates a proangiogenic and proinflammatory transcription factor, the nuclear factor kappa B (NF-κB), which has a master role in tumor progression, notably in pancreatic ductal adenocarcinoma and colorectal cancer. We identified a potent and specific small molecule inhibitor of PRMT5, PR5-LL-CM01, that dampens the methylation and activation of NF-κB. Here for the first time, we assessed the antiangiogenic activity of PR5-LL-CM01 in ocular cells. Immunostaining of human nvAMD sections revealed that PRMT5 is highly expressed in the retinal pigment epithelium (RPE)/choroid where neovascularization occurs, while mouse eyes with laser induced choroidal neovascularization (L-CNV) showed PRMT5 is overexpressed in the retinal ganglion cell layer and in the RPE/choroid. Importantly, inhibition of PRMT5 by PR5-LL-CM01 or shRNA knockdown of PRMT5 in human retinal endothelial cells (HRECs) and induced pluripotent stem cell (iPSC)-derived choroidal endothelial cells (iCEC2) reduced NF-κB activity and the expression of its target genes, such as tumor necrosis factor α (TNF-α) and VEGF-A. In addition to inhibiting angiogenic properties of proliferation and tube formation, PR5-LL-CM01 blocked cell cycle progression at G1/S-phase in a dose-dependent manner in these cells. Thus, we provide the first evidence that inhibition of PRMT5 impedes angiogenesis in ocular endothelial cells, suggesting PRMT5 as a potential therapeutic target to ameliorate ocular neovascularization.},
}
@article {pmid36720585,
year = {2024},
author = {Pandey, PU and Ballios, BG and Christakis, PG and Kaplan, AJ and Mathew, DJ and Ong Tone, S and Wan, MJ and Micieli, JA and Wong, JCY},
title = {Ensemble of deep convolutional neural networks is more accurate and reliable than board-certified ophthalmologists at detecting multiple diseases in retinal fundus photographs.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {3},
pages = {417-423},
pmid = {36720585},
issn = {1468-2079},
mesh = {Humans ; *Ophthalmologists ; *Deep Learning ; Fundus Oculi ; Neural Networks, Computer ; *Macular Degeneration/diagnostic imaging ; *Diabetic Retinopathy/diagnostic imaging ; *Glaucoma/diagnosis ; },
abstract = {AIMS: To develop an algorithm to classify multiple retinal pathologies accurately and reliably from fundus photographs and to validate its performance against human experts.<br><br>METHODS: We trained a deep convolutional ensemble (DCE), an ensemble of five convolutional neural networks (CNNs), to classify retinal fundus photographs into diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and normal eyes. The CNN architecture was based on the InceptionV3 model, and initial weights were pretrained on the ImageNet dataset. We used 43&#x2009;055 fundus images from 12 public datasets. Five trained ensembles were then tested on an 'unseen' set of 100 images. Seven board-certified ophthalmologists were asked to classify these test images.<br><br>RESULTS: Board-certified ophthalmologists achieved a mean accuracy of 72.7% over all classes, while the DCE achieved a mean accuracy of 79.2% (p=0.03). The DCE had a statistically significant higher mean F1-score for DR classification compared with the ophthalmologists (76.8% vs 57.5%; p=0.01) and greater but statistically non-significant mean F1-scores for glaucoma (83.9% vs 75.7%; p=0.10), AMD (85.9% vs 85.2%; p=0.69) and normal eyes (73.0% vs 70.5%; p=0.39). The DCE had a greater mean agreement between accuracy and confident of 81.6% vs 70.3% (p<0.001).<br><br>DISCUSSION: We developed a deep learning model and found that it could more accurately and reliably classify four categories of fundus images compared with board-certified ophthalmologists. This work provides proof-of-principle that an algorithm is capable of accurate and reliable recognition of multiple retinal diseases using only fundus photographs.},
}
@article {pmid36720212,
year = {2023},
author = {Kodaday, K and Kodjikian, L and Gadiollet, E and Chirpaz, N and Loria, O and Feldman, A and De Bats, F and Burillon, C and Denis, P and Pradat, P and Mathis, T},
title = {The Effects of Treatment Regimen on the Initial Management of Macular Neovascularization Subtypes in Age-Related Macular Degeneration.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {2},
pages = {113-122},
doi = {10.1159/000529409},
pmid = {36720212},
issn = {1423-0267},
mesh = {Humans ; *Angiogenesis Inhibitors/administration &amp; dosage/therapeutic use ; Follow-Up Studies ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Ranibizumab/administration &amp; dosage/therapeutic use ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {INTRODUCTION: The aim of this study was to evaluate the effect of initial treatment regimen individualization (pro re nata or treat-and-extend [TAE]), according to macular neovascularization (MNV) subtype, on the functional and anatomical response in neovascular age-related macular degeneration (nAMD). The secondary objective was to compare the treatment burden between each MNV subtype.<br><br>METHODS: Consecutive treatment-na&#xef;ve nAMD patients were retrospectively included. MNV subtype was graded by 2 independent blinded investigators on multimodal imaging. Functional and anatomical outcomes were analysed according to treatment regimen and MNV subtypes.<br><br>RESULTS: A total of 281 eyes from 243 patients were included in the study. According to the treatment regimen, there was no significant difference in best-corrected visual acuity gain within the first 2 years of treatment for type 1 (p = 0.106) and type 3 MNV (p = 0.704). Conversely, there was a significant difference in favour of TAE regimen for type 2 (p = 0.017) and type 4 MNV (p = 0.047). Type 1 MNV had a higher proportion of visits with subretinal fluid (p = 0.0007) but not with intraretinal fluid (p = 0.22). The mean interval between the last 2 injections was significantly shorter for type 1 MNV (p = 0.0045).<br><br>CONCLUSION: The individualization of the initial treatment protocol according to MNV subtype can improve the functional outcome and may decrease the treatment burden.},
}
@article {pmid36720210,
year = {2023},
author = {Kim, DJ and Jin, KW and Han, JM and Lee, SH and Park, YS and Lee, JY and Lee, EK and Lee, JS and Kim, ST and Shin, MH and Lee, CS and Jung, HH and Jang, JY and Kim, M and Kim, YH and Kim, JH and Park, KH and Park, SJ and Joo, K and Ji, YS and Sagong, M and Woo, SJ},
title = {Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {246},
number = {3-4},
pages = {192-202},
doi = {10.1159/000529410},
pmid = {36720210},
issn = {1423-0267},
mesh = {Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; *Retinal Vasculitis ; Inflammation ; Retina ; *Macular Degeneration ; },
abstract = {INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD).<br><br>METHODS: This multicenter retrospective study involved 294 eyes (treatment na&#xef;ve 20 eye [6.8%] and nontreatment na&#xef;ve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up &#x2265;1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid.<br><br>RESULTS: The mean age was 71.63 &#xb1; 8.66. The follow-up period was 2.38 &#xb1; 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 &#xb1; 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 &#xb1; 0.356 vs. 1 month 0.503 &#xb1; 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months.<br><br>CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.},
}
@article {pmid36717446,
year = {2022},
author = {Kolosova, NG and Kozhevnikova, OS and Muraleva, NA and Rudnitskaya, EA and Rumyantseva, YV and Stefanova, NA and Telegina, DV and Tyumentsev, MA and Fursova, AZ},
title = {SkQ1 as a Tool for Controlling Accelerated Senescence Program: Experiments with OXYS Rats.},
journal = {Biochemistry. Biokhimiia},
volume = {87},
number = {12},
pages = {1552-1562},
doi = {10.1134/S0006297922120124},
pmid = {36717446},
issn = {1608-3040},
mesh = {Animals ; Rats ; *Aging/physiology ; *Antioxidants/pharmacology ; Mitochondria/metabolism ; Oxidative Stress ; },
abstract = {According to the concept suggested by V. P. Skulachev and co-authors, aging of living organisms can be considered as a special case of programmed death of an organism - phenoptosis, and mitochondrial antioxidant SkQ1 is capable of inhibiting both acute and chronic phenoptosis (aging). The authors of the concept associate effects of SkQ1 with suppression of the enhanced generation of ROS in mitochondria. Numerous studies have confirmed the ability of SkQ1 to inhibit manifestations of the "healthy", or physiological, aging. According to the results of our studies, SkQ1 is especially effective in suppressing the program of genetically determined accelerated senescence in OXYS rats, which appears as an early development of a complex of age-related diseases: cataracts, retinopathy (similar to the age-related macular degeneration in humans), osteoporosis, and signs of Alzheimer's disease. Accelerated senescence in OXYS rats is associated with mitochondrial dysfunction, but no direct associations with oxidative stress have been identified. Nevertheless, SkQ1 is able to prevent and/or suppress development of all manifestations of accelerated senescence in OXYS rats. Its effects are due to impact on the activity of many signaling pathways and processes, but first of all they are associated with restoration of the structural and functional parameters of mitochondria. It could be suggested that the use of SkQ1 could represent a promising strategy in prevention of accelerated phenoptosis - early development of a complex of age-related diseases (multimorbidity) in people predisposed to it.},
}
@article {pmid36717001,
year = {2023},
author = {Hwang, S and Kang, SW and Kim, SJ and Han, K and Kim, BS and Jung, W and Lim, DH and Shin, DW},
title = {Impact of Age-Related Macular Degeneration and Related Visual Disability on the Risk of Depression: A Nationwide Cohort Study.},
journal = {Ophthalmology},
volume = {130},
number = {6},
pages = {615-623},
doi = {10.1016/j.ophtha.2023.01.014},
pmid = {36717001},
issn = {1549-4713},
mesh = {Humans ; Cohort Studies ; *Depression ; Risk Factors ; *Macular Degeneration/diagnosis/epidemiology/etiology ; Forecasting ; Incidence ; },
abstract = {PURPOSE: To evaluate the prospective association of age-related macular degeneration (AMD) and related visual disability (VD) with the risk of depression.<br><br>DESIGN: This nationwide population-based cohort study used authorized clinical data provided by the Korean National Health Insurance Service.<br><br>PARTICIPANTS: A total of 3 599 589 individuals older than 50 years participated in the Korean National Health Screening Program in&#xa0;2009.<br><br>METHODS: Age-related macular degeneration diagnosis and the presence of accompanying VD were verified using diagnostic codes and disability registration data. Data on covariates, including age, sex, income level, residential area, systemic comorbidities, and behavioral factors, were collected from health screening results and claims data. Patients were followed up until December 2019, and incident cases of depression were identified using registered diagnostic codes. The prospective association of AMD and related VD with new-onset depression was investigated using the multivariable-adjusted Cox proportional hazard model.<br><br>MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals (CIs) for depression development according to the presence of AMD and VD.<br><br>RESULTS: During an average follow-up period of 8.52 years, 1 037 088 patients received new diagnoses of depression. Patients with previous diagnoses of AMD showed a greater risk of new-onset depression, with a hazard ratio of 1.15 (95% CI, 1.13-1.17) compared with the control group in the fully adjusted model. Patients with AMD and accompanying VD showed a further increased risk of depression, with a hazard ratio of 1.23 (95% CI, 1.16-1.30).<br><br>CONCLUSIONS: Individuals with a diagnosis of AMD have a higher risk of depression developing in the future. The risk of depression is increased further in patients with AMD who demonstrate VD.<br><br>FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.},
}
@article {pmid36716636,
year = {2023},
author = {Zhang, Y and Huang, K and Li, M and Yuan, S and Chen, Q},
title = {Learn Single-horizon Disease Evolution for Predictive Generation of Post-therapeutic Neovascular Age-related Macular Degeneration.},
journal = {Computer methods and programs in biomedicine},
volume = {230},
number = {},
pages = {107364},
doi = {10.1016/j.cmpb.2023.107364},
pmid = {36716636},
issn = {1872-7565},
mesh = {Humans ; *Image Processing, Computer-Assisted/methods ; Tomography, Optical Coherence/methods ; *Macular Degeneration/diagnostic imaging ; },
abstract = {BACKGROUND AND OBJECTIVE: Most of the existing disease prediction methods in the field of medical image processing fall into two classes, namely image-to-category predictions and image-to-parameter predictions.Few works have focused on image-to-image predictions. Different from multi-horizon predictions in other fields, ophthalmologists prefer to show more confidence in single-horizon predictions due to the low tolerance of predictive risk.<br><br>METHODS: We propose a single-horizon disease evolution network (SHENet) to predictively generate post-therapeutic SD-OCT images by inputting pre-therapeutic SD-OCT images with neovascular age-related macular degeneration (nAMD). In SHENet, a feature encoder converts the input SD-OCT images to deep features, then a graph evolution module predicts the process of disease evolution in high-dimensional latent space and outputs the predicted deep features, and lastly, feature decoder recovers the predicted deep features to SD-OCT images. We further propose an evolution reinforcement module to ensure the effectiveness of disease evolution learning and obtain realistic SD-OCT images by adversarial training.<br><br>RESULTS: SHENet is validated on 383 SD-OCT cubes of 22 nAMD patients based on three well-designed schemes (P-0, P-1 and P-M) based on the quantitative and qualitative evaluations. Three metrics (PSNR, SSIM, 1-LPIPS) are used here for quantitative evaluations. Compared with other generative methods, the generative SD-OCT images of SHENet have the highest image quality (P-0: 23.659, P-1: 23.875, P-M: 24.198) by PSNR. Besides, SHENet achieves the best structure protection (P-0: 0.326, P-1: 0.337, P-M: 0.349) by SSIM and content prediction (P-0: 0.609, P-1: 0.626, P-M: 0.642) by 1-LPIPS. Qualitative evaluations also demonstrate that SHENet has a better visual effect than other methods.<br><br>CONCLUSIONS: SHENet can generate post-therapeutic SD-OCT images with both high prediction performance and good image quality, which has great potential to help ophthalmologists forecast the therapeutic effect of nAMD.},
}
@article {pmid36716039,
year = {2023},
author = {Chen, X and Xue, Y and Wu, X and Zhong, Y and Rao, H and Luo, H and Weng, Z},
title = {Deep Learning-Based System for Disease Screening and Pathologic Region Detection From Optical Coherence Tomography Images.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {1},
pages = {29},
pmid = {36716039},
issn = {2164-2591},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Deep Learning ; *Retinal Diseases/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; },
abstract = {PURPOSE: This study was designed to apply deep learning models in retinal disease screening and lesion detection based on optical coherence tomography (OCT) images.<br><br>METHODS: We collected 37,138 OCT images from 775 patients and labelled by ophthalmologists. Multiple deep learning models including ResNet50 and YOLOv3 were developed to identify the types and locations of diseases or lesions based on the images.<br><br>RESULTS: The model were evaluated using patient-based independent holdout set. For binary classification of OCT images with or without lesions, the performance accuracy was 98.5%, sensitivity was 98.7%, specificity was 98.4%, and the F1 score was 97.7%. For multiclass multilabel disease classification, the models was able to detect vitreomacular traction syndrome and age-related macular degeneration both with an accuracy of more than 99%, sensitivity of more than 98%, specificity of more than 98%, and an F1 score of more than 97%. For lesion location detection, the recalls for different lesion types ranged from 87.0% (epiretinal membrane) to 98.2% (macular pucker).<br><br>CONCLUSIONS: Deep learning-based models have potentials to aid retinal disease screening, classification and diagnosis with excellent performance, which may serve as useful references for ophthalmologists.<br><br>TRANSLATIONAL RELEVANCE: The deep learning-based models are capable of identifying and predicting different eye diseases and lesions from OCT images and may have potential clinical application to assist the ophthalmologists for fast and accuracy retinal disease screening.},
}
@article {pmid36709332,
year = {2023},
author = {Koidala, SP and Manne, SR and Ozimba, K and Rasheed, MA and Bashar, SB and Ibrahim, MN and Selvam, A and Sahel, JA and Chhablani, J and Jana, S and Vupparaboina, KK},
title = {Deep learning based diagnostic quality assessment of choroidal OCT features with expert-evaluated explainability.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {1570},
pmid = {36709332},
issn = {2045-2322},
support = {P30 EY008098/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Choroid/diagnostic imaging/blood supply ; *Choroid Diseases/diagnostic imaging ; *Deep Learning ; Tomography, Optical Coherence/methods ; },
abstract = {Various vision-threatening eye diseases including age-related macular degeneration (AMD) and central serous chorioretinopathy (CSCR) are caused due to the dysfunctions manifested in the highly vascular choroid layer of the posterior segment of the eye. In the current clinical practice, screening choroidal structural changes is widely based on optical coherence tomography (OCT) images. Accordingly, to assist clinicians, several automated choroidal biomarker detection methods using OCT images are developed. However, the performance of these algorithms is largely constrained by the quality of the OCT scan. Consequently, determining the quality of choroidal features in OCT scans is significant in building standardized quantification tools and hence constitutes our main objective. This study includes a dataset of 1593 good and 2581 bad quality Spectralis OCT images graded by an expert. Noting the efficacy of deep-learning (DL) in medical image analysis, we propose to train three state-of-the-art DL models: ResNet18, EfficientNet-B0 and EfficientNet-B3 to detect the quality of OCT images. The choice of these models was inspired by their ability to preserve the salient features across all the layers without information loss. To evaluate the attention of DL models on the choroid, we introduced color transparency maps (CTMs) based on GradCAM explanations. Further, we proposed two subjective grading scores: overall choroid coverage (OCC) and choroid coverage in the visible region(CCVR) based on CTMs to objectively correlate visual explanations vis-à-vis DL model attentions. We observed that the average accuracy and F-scores for the three DL models are greater than 96%. Further, the OCC and CCVR scores achieved for the three DL models under consideration substantiate that they mostly focus on the choroid layer in making the decision. In particular, of the three DL models, EfficientNet-B3 is in close agreement with the clinician's inference. The proposed DL-based framework demonstrated high detection accuracy as well as attention on the choroid layer, where EfficientNet-B3 reported superior performance. Our work assumes significance in bench-marking the automated choroid biomarker detection tools and facilitating high-throughput screening. Further, the methods proposed in this work can be adopted for evaluating the attention of DL-based approaches developed for other region-specific quality assessment tasks.},
}
@article {pmid36707779,
year = {2023},
author = {Tsai, CY and Wu, CL and Cheng, CK and Shen, YD and Wu, WC and Wu, PC and Tsai, A and Chen, JT},
title = {Baseline characteristics and treatment response predictive of nAMD outcomes with ranibizumab therapy in treatment-naive patients: the RACER subgroup analysis.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {39},
pmid = {36707779},
issn = {1471-2415},
mesh = {Adult ; Humans ; *Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; *Ranibizumab/therapeutic use ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; },
abstract = {BACKGROUND: The Ranibizumab AMD Clinical Efficacy Study (RACER) conducted in treatment-naive adult Taiwanese patients with neovascular age-related macular degeneration (nAMD) suggested the importance of early and intensive dosing of ranibizumab for optimal treatment outcomes. This subgroup analysis aims to provide clinical information on treatment response that can potentially guide on maintaining the treatment or switching anti-VEGF agents in the real-world setting.<br><br>METHODS: Visual acuity (VA) and central retinal thickness (CRT) were assessed in the RACER subgroup population. Subgroup analysis sets were categorised based on: (1) baseline best-corrected VA (BCVA;&#x2009;&#x2264;&#x2009;48 and&#x2009;>&#x2009;48 letters); (2) baseline CRT (&#x2264;&#x2009;325 or&#x2009;>&#x2009;325&#xa0;&#x3bc;m); and (3) treatment response after three monthly initial injections:&#x2009;<&#x2009;or&#x2009;&#x2265;&#x2009;5-letter gain in BCVA and reduction of&#x2009;<&#x2009;or&#x2009;&#x2265;&#x2009;50&#xa0;&#x3bc;m in CRT.<br><br>RESULTS: Patient age, sex, nAMD duration and number of ranibizumab injections did not differ significantly between the treatment subgroups. Poor baseline BCVA (&#x2264;&#x2009;48 letters) and baseline CRT severity (>&#x2009;325&#xa0;&#xb5;m) were predictors of maximum BCVA gains (9.6&#x2009;&#xb1;&#x2009;12.9 letters [95%CI: 6.3 to 12.9] and 5.1&#x2009;&#xb1;&#x2009;18.3 letters [95%CI:&#x2009;-&#x2009;0.5 to 10.8] at Months 3 and 12, respectively) and better CRT reductions (-&#x2009;127.6&#x2009;&#xb1;&#x2009;104.2&#xa0;&#xb5;m and&#x2009;-&#x2009;104.2&#x2009;&#xb1;&#x2009;107.4&#xa0;&#xb5;m at Months 3 and 12, respectively; both P&#x2009;<&#x2009;0.001). For the subgroup showing favourable treatment improvement with BCVA gains&#x2009;&#x2265;&#x2009;5 letters after three monthly initial injections, 75.6% of patients maintained follow-up at Month 12 with a mean of 6.5&#x2009;&#xb1;&#x2009;14.3 letter gains (95% CI: 1.2 to 11.7). The BCVA gains&#x2009;<&#x2009;5-letter subgroup nevertheless had stable BCVA (0.4&#x2009;&#xb1;&#x2009;12.1 letter gains) and CRT (-&#x2009;41.9&#x2009;&#xb1;&#x2009;61.2&#xa0;&#xb5;m) at Month 12, respectively. In the subgroup with&#x2009;&#x2265;&#x2009;50&#xa0;&#xb5;m CRT reduction after three monthly initial injections, there are significantly higher BCVA improvements vs. the&#x2009;<&#x2009;50&#xa0;&#xb5;m CRT reduction subgroup at Month 3 (5.0&#x2009;&#xb1;&#x2009;8.6 letter gains vs. 1.5&#x2009;&#xb1;&#x2009;11.6 letter gains, respectively; intergroup P&#x2009;=&#x2009;0.005).<br><br>CONCLUSION: Lower baseline BCVA and higher baseline CRT were associated with BCVA gains and CRT reductions throughout the 12-month study period. Early CRT improvements after three monthly initial injections were associated with BCVA gains as early as Month 3.},
}
@article {pmid36707303,
year = {2023},
author = {Liu, G and Li, Y},
title = {Re: Zekavat et al.: Photoreceptor layer thinning is an early biomarker for age-related macular degeneration: epidemiological and genetic evidence from UK Biobank OCT data (Ophthalmology. 2022;129:694-707).},
journal = {Ophthalmology},
volume = {130},
number = {4},
pages = {e15},
doi = {10.1016/j.ophtha.2022.12.002},
pmid = {36707303},
issn = {1549-4713},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Tomography, Optical Coherence ; Biological Specimen Banks ; *Macular Degeneration/diagnosis/epidemiology/genetics ; Biomarkers ; United Kingdom/epidemiology ; },
}
@article {pmid36705991,
year = {2023},
author = {Oakley, JD and Verdooner, S and Russakoff, DB and Brucker, AJ and Seaman, J and Sahni, J and Bianchi, CD and Cozzi, M and Rogers, J and Staurenghi, G},
title = {QUANTITATIVE ASSESSMENT OF AUTOMATED OPTICAL COHERENCE TOMOGRAPHY IMAGE ANALYSIS USING A HOME-BASED DEVICE FOR SELF-MONITORING NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {3},
pages = {433-443},
pmid = {36705991},
issn = {1539-2864},
mesh = {Humans ; Tomography, Optical Coherence/methods ; Retina ; Subretinal Fluid ; Software ; *Macular Degeneration/diagnosis ; *Wet Macular Degeneration ; Angiogenesis Inhibitors ; },
abstract = {PURPOSE: To evaluate a prototype home optical coherence tomography device and automated analysis software for detection and quantification of retinal fluid relative to manual human grading in a cohort of patients with neovascular age-related macular degeneration.<br><br>METHODS: Patients undergoing anti-vascular endothelial growth factor therapy were enrolled in this prospective observational study. In 136 optical coherence tomography scans from 70 patients using the prototype home optical coherence tomography device, fluid segmentation was performed using automated analysis software and compared with manual gradings across all retinal fluid types using receiver-operating characteristic curves. The Dice similarity coefficient was used to assess the accuracy of segmentations, and correlation of fluid areas quantified end point agreement.<br><br>RESULTS: Fluid detection per B-scan had area under the receiver-operating characteristic curves of 0.95, 0.97, and 0.98 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively. On a per volume basis, the values for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid were 0.997, 0.998, and 0.998, respectively. The average Dice similarity coefficient values across all B-scans were 0.64, 0.73, and 0.74, and the coefficients of determination were 0.81, 0.93, and 0.97 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively.<br><br>CONCLUSION: Home optical coherence tomography device images assessed using the automated analysis software showed excellent agreement to manual human grading.},
}
@article {pmid36705929,
year = {2023},
author = {Saßmannshausen, M and Vaisband, M and von der Emde, L and Sloan, KR and Hasenauer, J and Holz, FG and Ach, T},
title = {Hyper-Reflective Foci in Intermediate Age-Related Macular Degeneration: Spatial Abundance and Impact on Retinal Morphology.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {1},
pages = {20},
pmid = {36705929},
issn = {1552-5783},
mesh = {Humans ; Middle Aged ; Aged ; *Retinal Drusen/diagnosis/pathology ; Retina/diagnostic imaging/pathology ; *Macular Degeneration/diagnosis/pathology ; Retinal Pigment Epithelium/pathology ; Visual Field Tests ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: The purpose of this study was to analyze spatially resolved structural changes at retinal locations in presence (+) or absence (-) of hyper-reflective foci (HRF) in eyes with subretinal pigment epithelium (RPE) drusen in intermediate age-related macular degeneration (iAMD).<br><br>METHODS: Patients with IAMD (n = 40; mean age = 69.7 &#xb1; 9.2 [SD] years) and healthy controls (n = 27; 64.2 &#xb1; 9.0) underwent spectral-domain optical-coherence-tomography imaging and fundus-controlled perimetry testing. After reviewing retinal layer segmentation, presence of HRF was annotated and retinal layer thicknesses (RLTs) extracted using ImageJ. Localized RLTs were compared between +HRF and -HRF positions. Univariate mixed linear models were used to investigate associations among RLT, HRF presence, and HRF size.<br><br>RESULTS: In iAMD eyes, a mean of 11.1 &#xb1; 12.5 HRF were detected with a peak abundance at 0.5 to 1.5 mm eccentricity to the fovea. At +HRF positions, outer nuclear layer (ONL; P = 0.0013, average difference = -12.4 &#xb5;m) and retinal pigment epithelium drusen complex (RPEDC; P < 0.0001, +45.6 &#xb5;m) thicknesses differed significantly compared to -HRF positions, even after correcting for accompanying drusen-related RPEDC layer thickening (P = 0.01). Mixed linear models revealed a significant association between increasing HRF area and decreasing ONL (association score = -0.17, P < 0.0001; 95% confidence interval [CI] = -0.22 to -0.11), and inner photoreceptor segments (IS) layer thicknesses (-0.08, P = 0.005; 95% CI = -0.14 to -0.03). Spearman rank correlation analysis yielded a significant correlation between total HRF area and mesopic (P = 0.015), but not scotopic (P = 0.305) retinal sensitivity losses.<br><br>CONCLUSIONS: Descriptive analysis of this study demonstrated a predominant distribution of HRF at a foveal eccentricity of 0.5 to 1.5 mm, whereas further refined topographic analysis revealed a significant ONL layer thinning in presence of HRF even after correction for sub-RPE drusen presence compared to lesions in absence of HRF. Longitudinal studies are further needed to analyze the prognostic impact as well as the role of HRF presence in the context of iAMD.},
}
@article {pmid36705323,
year = {2023},
author = {Julian, TH and Cooper-Knock, J and MacGregor, S and Guo, H and Aslam, T and Sanderson, E and Black, GCM and Sergouniotis, PI},
title = {Phenome-wide Mendelian randomisation analysis identifies causal factors for age-related macular degeneration.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {36705323},
issn = {2050-084X},
support = {Academic Clinical Fellow and Clinical Lecturer Programmes/DH_/Department of Health/United Kingdom ; 224643/Z/21/Z/WT_/Wellcome Trust/United Kingdom ; 200990/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 204796/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; 216596/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Risk Factors ; Bayes Theorem ; Australia ; *Macular Degeneration/genetics ; Causality ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in the industrialised world and is projected to affect >280 million people worldwide by 2040. Aiming to identify causal factors and potential therapeutic targets for this common condition, we designed and undertook a phenome-wide Mendelian randomisation (MR) study.<br><br>METHODS: We evaluated the effect of 4591 exposure traits on early AMD using univariable MR. Statistically significant results were explored further using: validation in an advanced AMD cohort; MR Bayesian model averaging (MR-BMA); and multivariable MR.<br><br>RESULTS: Overall, 44 traits were found to be putatively causal for early AMD in univariable analysis. Serum proteins that were found to have significant relationships with AMD included S100-A5 (odds ratio [OR] = 1.07, p-value = 6.80E-06), cathepsin F (OR = 1.10, p-value = 7.16E-05), and serine palmitoyltransferase 2 (OR = 0.86, p-value = 1.00E-03). Univariable MR analysis also supported roles for complement and immune cell traits. Although numerous lipid traits were found to be significantly related to AMD, MR-BMA suggested a driving causal role for serum sphingomyelin (marginal inclusion probability [MIP] = 0.76; model-averaged causal estimate [MACE] = 0.29).<br><br>CONCLUSIONS: The results of this MR study support several putative causal factors for AMD and highlight avenues for future translational research.<br><br>FUNDING: This project was funded by the Wellcome Trust (224643/Z/21/Z; 200990/Z/16/Z); the University of Manchester's Wellcome Institutional Strategic Support Fund (Wellcome ISSF) grant (204796/Z/16/Z); the UK National Institute for Health Research (NIHR) Academic Clinical Fellow and Clinical Lecturer Programmes; Retina UK and Fight for Sight (GR586); the Australian National Health and Medical Research Council (NHMRC) (1150144).},
}
@article {pmid36705252,
year = {2023},
author = {Eichenbaum, D and Brown, DM and Ip, M and Khanani, AM and Figueroa, MS and McAllister, IL and Laude, A and B, G and Tang, S and Gmeiner, B and Clemens, A and Souied, E},
title = {IMPACT OF RETINAL FLUID-FREE MONTHS ON OUTCOMES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Treatment Agnostic Analysis of the HAWK and HARRIER Studies.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {4},
pages = {632-640},
pmid = {36705252},
issn = {1539-2864},
mesh = {Humans ; Animals ; Angiogenesis Inhibitors/therapeutic use ; *Hawks ; Visual Acuity ; Intravitreal Injections ; Tomography, Optical Coherence ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Birds ; *Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/therapeutic use ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: To assess the effect of the total number of fluid-free months after loading on visual and anatomical outcomes in neovascular age-related macular degeneration patients receiving anti-vascular endothelial growth factor therapy.<br><br>METHODS: This post hoc analysis pooled patient-level data from the brolucizumab 6 mg (n = 718) and aflibercept 2 mg (n = 715) arms of the HAWK and HARRIER randomized clinical trials. Based on data from Weeks 12 to 96, patients were assigned to one of five categories based on fluid-free visits (FFVs; the total number of monthly visits at which they were observed to be without retinal fluid). Three definitions of "fluid-free" were explored based on the location of the fluid observed.<br><br>RESULTS: Patients allocated to Categories 4 (15-21 FFV) and 5 (22 FFV, always dry) consistently had the best visual and anatomical outcomes at Week 96, whereas patients allocated to Categories 1 (0 FFV, never dry) and 2 (1-7 FFV) consistently had the worst visual and anatomical outcomes. Variability in retinal thickness over time was lowest in Categories 4 and 5.<br><br>CONCLUSION: Absence of retinal fluid at more visits after loading has a positive association with visual and anatomic outcomes in neovascular age-related macular degeneration patients, regardless of fluid type.},
}
@article {pmid36704044,
year = {2022},
author = {Liu, K and Fan, H and Hu, H and Cheng, Y and Liu, J and You, Z},
title = {Genetic variation reveals the influence of steroid hormones on the risk of retinal neurodegenerative diseases.},
journal = {Frontiers in endocrinology},
volume = {13},
number = {},
pages = {1088557},
pmid = {36704044},
issn = {1664-2392},
mesh = {Humans ; Aldosterone ; Estradiol ; Genetic Variation ; Genome-Wide Association Study ; *Neurodegenerative Diseases ; *Retinal Diseases ; Steroids ; Mendelian Randomization Analysis ; },
abstract = {It is difficult to get evidence from randomized trials of a causal relationship between steroid hormones produced by the adrenal gland and gonad and retinal neurodegenerative disorders (RND). In this study, genetic variations of aldosterone (Aldo), androstenedione (A4), progesterone (P4), hydroxyprogesterone (17-OHP), and testosterone/17β-estradiol (T/E2) were obtained from genome-wide association studies as instrumental variables. Mendelian randomization (MR) analysis was used to assess the impact on the risk of RND, including glaucoma (8,591 cases and 210,201 controls), diabetic retinopathy (DR, 14,584 cases and 202,082 controls) and age-related macular degeneration (AMD, 14,034 cases and 91,214 controls). As the main method, inverse variance weighted results suggest that the increased glaucoma risk was affected by T/E2 (OR = 1.11, 95% CI, 1.01-1.22, P = 0.03), which was further validated by other methods (PWM = 0.03, PMLE = 0.03, PMR-RAPS = 0.03). In the replicated stage, the causal relationship between T/E2 and glaucoma was verified based on the MRC-IEU consortium (P = 0.04). No impact of Aldo, A4, P4, 17-OHP, and T/E2 was observed for the risk of DR (P > 0.05) and AMD (P > 0.05). The heterogeneity test (P > 0.05) and pleiotropy test (P > 0.05) verified the robustness of the results. Our results suggest that T/E2 has a suggestive effect on the glaucoma risk. However, the genetic evidence based on a large sample does not support the effect of steroid hormones on DR and AMD risk. Further studies are vital to assess the possibility of steroid hormones as targets for prevention and treatment.},
}
@article {pmid36703913,
year = {2023},
author = {Zhang, S and Qiu, Y and Feng, Y and Zhang, Y and Li, Y and Wang, B and Wei, H and Chen, X and Shen, L and Li, W and Zheng, L and Zhang, Y},
title = {Calpain-2 Facilitates Autophagic/Lysosomal Defects and Apoptosis in ARPE-19 Cells and Rats Induced by Exosomes from RPE Cells under NaIO3 Stimulation.},
journal = {Oxidative medicine and cellular longevity},
volume = {2023},
number = {},
pages = {3310621},
pmid = {36703913},
issn = {1942-0994},
mesh = {Animals ; Rats ; *Apoptosis ; *Autophagy ; *Calpain/metabolism ; *Exosomes ; Lysosomes ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Although accumulated evidence supports the notion that calpain contributes to eye disease, the mechanisms by which calpain promotes RPE injury are not defined. The present study is aimed at investigating whether the effect of NaIO3-exos (exosomes derived from RPE cells under NaIO3 stimulation) on the dysfunction of the autophagy-lysosomal pathway (ALP) and apoptosis is based on its regulation of calpain activation in ARPE-19 cells and rats. The results showed that calpain-2 activation, ALP dysfunction, and apoptosis were induced by NaIO3-exos in ARPE-19 cells. NaIO3-exo significantly increased autophagic substrates by activating lysosomal dysfunction. ALP dysfunction and apoptosis in vitro could be eliminated by knocking down calpain-2 (si-C2) or the inhibitor calpain-2-IN-1. Further studies indicated that NaIO3-exo enhanced calpain-2 expression, ALP dysfunction, apoptosis, and retinal damage in rats. In summary, these results demonstrate for the first time that calpain-2 is one of the key players in the NaIO3-exo-mediated ALP dysfunction, apoptosis, and retinal damage and identify calpain-2 as a promising target for therapies aimed at age-related macular degeneration (AMD).},
}
@article {pmid36703888,
year = {2022},
author = {Paguaga, ME and Penn, JS and Uddin, MI},
title = {A novel optical imaging probe for targeted visualization of NLRP3 inflammasomes in a mouse model of age-related macular degeneration.},
journal = {Frontiers in medicine},
volume = {9},
number = {},
pages = {1047791},
pmid = {36703888},
issn = {2296-858X},
support = {R01 EY023397/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Wet form of age-related macular degeneration (wet AMD) is a progressive vascular disease that mainly affects older adults and causes severe and irreversible vision loss. A key complication of wet AMD is choroidal neovascularization (CNV), which may be driven in part by NLRP3 inflammasomes that are associated with macrophages migration to CNV lesions. Since activated NLRP3 is correlated with CNV, visualizing NLRP3 inflammasomes and their associated macrophages is of great interest to monitor wet AMD progression and develop effective therapies against it. However, to the best of our knowledge, current ophthalmic imaging systems do not permit such targeted imaging. Therefore, in this study, we developed InflammaProbe-1, an optical imaging probe for targeted visualization of NLRP3 inflammasomes in CNV lesions.<br><br>METHODS: InflammaProbe-1 was synthesized by conjugating a clinically relevant fluorophore, Oregon Green[&#xae;] 488, to the selective NLRP3 inhibitor, CY-09. The ability of InflammaProbe-1 to target NLRP3 was assessed with an enzyme-linked immunosorbent assay by comparing its ability to inhibit NLRP3-mediated secretion of IL-1&#x3b2; to that of CY-09 in LPS-primed and nigericin-stimulated BMDMs. In vitro confocal imaging of NLRP3 was performed on InflammaProbe-1-stained BMDMs that had been induced to express NLRP3 with LPS. In vivo imaging of NLRP3 was conducted on mouse laser induced choroidal neovascularization (LCNV), a model of AMD, 6 h after an intraperitoneal injection of InflammaProbe-1 at 10 mg/kg on day 4 post-LCNV.<br><br>RESULTS: InflammaProbe-1 was just as effective as CY-09 at inhibiting IL-1&#x3b2; secretion (p < 0.01 at 10 &#x3bc;M for both the InflammaProbe-1 and CY-09 groups relative to the control). InflammaProbe-1-stained BMDMs that had been induced to express NLRP3 showed significantly brighter fluorescence than untreated cells (p < 0.0001 for LPS treatment group and p < 0.001 for LPS and nigericin treatment group). Furthermore, in vivo molecular imaging of NLRP3 was achieved in mouse LCNV.<br><br>CONCLUSION: We propose that InflammaProbe-1 may be a useful molecular imaging probe to monitor the onset, progression, and therapeutic response of AMD and other NLRP3-mediated diseases.},
}
@article {pmid36702141,
year = {2023},
author = {Liu, H and Li, R and Zhang, Y and Zhang, K and Yusufu, M and Liu, Y and Mou, D and Chen, X and Tian, J and Li, H and Fan, S and Tang, J and Wang, N},
title = {Economic evaluation of combined population-based screening for multiple blindness-causing eye diseases in China: a cost-effectiveness analysis.},
journal = {The Lancet. Global health},
volume = {11},
number = {3},
pages = {e456-e465},
doi = {10.1016/S2214-109X(22)00554-X},
pmid = {36702141},
issn = {2214-109X},
mesh = {Humans ; Middle Aged ; Aged ; Cost-Benefit Analysis ; Cost-Effectiveness Analysis ; Artificial Intelligence ; *Ophthalmology ; *Telemedicine ; *Glaucoma/diagnosis ; China/epidemiology ; Quality-Adjusted Life Years ; },
abstract = {BACKGROUND: More than 90% of vision impairment is avoidable. However, in China, a routine screening programme is currently unavailable in primary health care. With the dearth of economic evidence on screening programmes for multiple blindness-causing eye diseases, delivery options, and screening frequencies, we aimed to evaluate the costs and benefits of a population-based screening programme for multiple eye diseases in China.<br><br>METHODS: We developed a decision-analytic Markov model for a cohort of individuals aged 50 years and older with a total of 30 1-year cycles. We calculated the cost-effectiveness and cost-utility of screening programmes for multiple major blindness-causing eye diseases in China, including age-related macular degeneration, glaucoma, diabetic retinopathy, cataracts, and pathological myopia, from a societal perspective (including direct and indirect costs). We analysed rural and urban settings separately by different screening delivery options (non-telemedicine [ie, face-to-face] screening, artificial intelligence [AI] telemedicine screening, and non-AI telemedicine screening) and frequencies. We calculated incremental cost-utility ratios (ICURs) using quality-adjusted life-years and incremental cost-effectiveness ratios (ICERs) in terms of the cost per blindness year avoided. One-way deterministic and simulated probabilistic sensitivity analyses were used to assess the robustness of the main outcomes.<br><br>FINDINGS: Compared with no screening, non-telemedicine combined screening of multiple eye diseases satisfied the criterion for a highly cost-effective health intervention, with an ICUR of US$2494 (95% CI 1130 to 2716) and an ICER of $12&#x2009;487 (8773 to 18&#x2009;791) in rural settings. In urban areas, the ICUR was $624 (395 to 907), and the ICER was $7251 (4238 to 13&#x2009;501). Non-AI telemedicine screening could result in fewer costs and greater gains in health benefits (ICUR $2326 [1064 to 2538] and ICER $11&#x2009;766 [8200 to 18&#x2009;000] in rural settings; ICUR $581 [368 to 864] and ICER $6920 [3926 to 13&#x2009;231] in urban settings). AI telemedicine screening dominated no screening in rural settings, and in urban settings the ICUR was $244 (-315 to 1073) and the ICER was $2567 (-4111 to 15&#x2009;389). Sensitivity analyses showed all results to be robust. By further comparison, annual AI telemedicine screening was the most cost-effective strategy in both rural and urban areas.<br><br>INTERPRETATION: Combined screening of multiple eye diseases is cost-effective in both rural and urban China. AI coupled with teleophthalmology presents an opportunity to promote equity in eye health.<br><br>FUNDING: National Natural Science Foundation of China.},
}
@article {pmid36701964,
year = {2023},
author = {Moradi, M and Chen, Y and Du, X and Seddon, JM},
title = {Deep ensemble learning for automated non-advanced AMD classification using optimized retinal layer segmentation and SD-OCT scans.},
journal = {Computers in biology and medicine},
volume = {154},
number = {},
pages = {106512},
pmid = {36701964},
issn = {1879-0534},
support = {R01 EY011309/EY/NEI NIH HHS/United States ; R01 EY028602/EY/NEI NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retina/diagnostic imaging ; *Macular Degeneration/diagnostic imaging ; Algorithms ; Machine Learning ; },
abstract = {BACKGROUND: Accurate retinal layer segmentation in optical coherence tomography (OCT) images is crucial for quantitatively analyzing age-related macular degeneration (AMD) and monitoring its progression. However, previous retinal segmentation models depend on experienced experts and manually annotating retinal layers is time-consuming. On the other hand, accuracy of AMD diagnosis is directly related to the segmentation model's performance. To address these issues, we aimed to improve AMD detection using optimized retinal layer segmentation and deep ensemble learning.<br><br>METHOD: We integrated a graph-cut algorithm with a cubic spline to automatically annotate 11 retinal boundaries. The refined images were fed into a deep ensemble mechanism that combined a Bagged Tree and end-to-end deep learning classifiers. We tested the developed deep ensemble model on internal and external datasets.<br><br>RESULTS: The total error rates for our segmentation model using the boundary refinement approach was significantly lower than OCT Explorer segmentations (1.7% vs. 7.8%, p-value&#xa0;=&#xa0;0.03). We utilized the refinement approach to quantify 169 imaging features using Zeiss SD-OCT volume scans. The presence of drusen and thickness of total retina, neurosensory retina, and ellipsoid zone to inner-outer segment (EZ-ISOS) thickness had higher contributions to AMD classification compared to other features. The developed ensemble learning model obtained a higher diagnostic accuracy in a shorter time compared with two human graders. The area under the curve (AUC) for normal vs. early AMD was 99.4%.<br><br>CONCLUSION: Testing results showed that the developed framework is repeatable and effective as a potentially valuable tool in retinal imaging research.},
}
@article {pmid36698793,
year = {2022},
author = {Türksever, C and Hoffmann, L and Hatz, K},
title = {Peripapillary and macular microvasculature in neovascular age-related macular degeneration in long-term and recently started anti-VEGF therapy versus healthy controls.},
journal = {Frontiers in medicine},
volume = {9},
number = {},
pages = {1080052},
pmid = {36698793},
issn = {2296-858X},
abstract = {AIM: To investigate the peripapillary and macular microvasculature in neovascular age-related macular degeneration (nAMD) in recently started versus long-term anti-vascular endothelial growth factor (VEGF) therapy and healthy controls.<br><br>METHODS: Eyes with nAMD treated in a treat-and-extend regimen were assigned to group 1 (<5 injections) or 2 (&#x2265;20 injections) whereas group 3 constituted the healthy age-matched controls. Blood flow signals were acquired using PLEX[&#xae;] Elite 9000 swept-source optical coherence tomography angiography (OCTA) of the macular and peripapillary regions. Mean ganglion cell complex (GCC) thickness values were quantified using spectral-domain optical coherence tomography (SD-OCT).<br><br>RESULTS: Including 80 eyes whereof 40 controls, macular superficial perfusion density was significantly reduced in group 1 and 2 compared to controls (p < 0.001; p = 0.010) without a difference between groups 1 and 2. Peripapillary perfusion parameters did not correlate with post-operative intraocular pressure (IOP) or number of anti-VEGF injections. Mean peripapillary flux index was significantly lower in group 2 than in controls (p = 0.023) and significantly decreased in the nasal quadrants for both AMD groups compared to group 3 (p = 0.013; p < 0.001). Mean peripapillary perfusion density was significantly reduced in both AMD groups compared to controls (0.515 &#xb1; 0.02 versus 0.556 &#xb1; 0.03, p < 0.0001).<br><br>CONCLUSION: Frequency of anti-VEGF treatment in nAMD and post-operative IOP showed no correlation with peripapillary perfusion parameters, but anti-VEGF treated nAMD patients exhibited partly altered peripapillary perfusion compared to healthy controls. Reduced macular perfusion density of the inner retina in anti-VEGF treated nAMD compared to healthy controls might be discussed as an anti-VEGF treatment effect or a characteristic of nAMD.},
}
@article {pmid36698471,
year = {2022},
author = {García-Montalvo, IA and Matías-Pérez, D and Hernández-Bautista, E and Pérez-Campos, E},
title = {Inclusion of carotenoids in dietary habits as an alternative to prevent age-related macular degeneration.},
journal = {Frontiers in nutrition},
volume = {9},
number = {},
pages = {1063517},
pmid = {36698471},
issn = {2296-861X},
}
@article {pmid36697902,
year = {2023},
author = {Vu, KV and Mitchell, P and Detaram, HD and Burlutsky, G and Liew, G and Gopinath, B},
title = {Risk factors for poorer quality of life in patients with neovascular age-related macular degeneration: a longitudinal clinic-based study.},
journal = {Eye (London, England)},
volume = {37},
number = {13},
pages = {2736-2743},
pmid = {36697902},
issn = {1476-5454},
support = {N/A//Macular Disease Foundation Australia (MDFA)/ ; },
mesh = {Humans ; *Quality of Life/psychology ; Activities of Daily Living ; Vision, Ocular ; Surveys and Questionnaires ; *Macular Degeneration ; Risk Factors ; Sickness Impact Profile ; },
abstract = {BACKGROUND/OBJECTIVES: To examine the risk factors for poor vision-related and health-related quality of life (QoL) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (anti-VEGF) therapy.<br><br>METHODS: In a clinic-based cohort of 547 nAMD patients who presented for treatment, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ25), Short-Form 36 (SF-36) and EuroQoL EQ-5D-5L questionnaires were administered to assess vision-related and health-related QoL. Of these, 83 participants were followed up one-year later to provide longitudinal data.<br><br>RESULTS: Individuals with mild or moderate visual impairment or blindness at baseline had significantly lower NEI-VFQ-25 scores at follow-up. The presence of &#x2265;3 chronic diseases was associated with lower SF-36 mental component scores (MCS) (p&#x2009;=&#x2009;0.04) and EQ-VAS scores (p&#x2009;=&#x2009;0.05). Depressive symptoms were associated with significantly lower MCS (p&#x2009;<&#x2009;0.0001) and EQ-VAS scores (p&#x2009;=&#x2009;0.02). Individuals with versus without impaired basic activities of daily living (ADLs) exhibited NEI-VFQ-25 and EQ-VAS scores that were 10.96 (p&#x2009;=&#x2009;0.03) and 0.13 (p&#x2009;=&#x2009;0.02) points lower. Those with impaired instrumental ADLs scored 11.62 (p&#x2009;=&#x2009;0.02), 13.13 (p&#x2009;<&#x2009;0.0001) and 15.8 (p&#x2009;=&#x2009;0.0012) points lower in the NEI-VFQ-25, SF-36 physical component score and EQ-5D-5L summary score, respectively.<br><br>CONCLUSIONS: The QoL of nAMD patients is affected by visual acuity as well as patients' medical history, mental health and functional status.},
}
@article {pmid36697379,
year = {2023},
author = {Zhu, AS and Lin, JC and Kang, C and Qureshi, R and Scherer, RW and Greenberg, PB},
title = {Predictors of Citations for Original Research in Ophthalmology.},
journal = {Seminars in ophthalmology},
volume = {38},
number = {4},
pages = {398-401},
pmid = {36697379},
issn = {1744-5205},
support = {UG1 EY020522/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; United States ; *Ophthalmology ; Journal Impact Factor ; },
abstract = {There is a dearth of literature on factors associated with citation of publications in ophthalmology. We investigated predictors of citations for original ophthalmologic research articles based on author, study, and journal characteristics. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), we extracted articles that studied the leading cause of vision impairment in the United States (cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma) and were published in the top fifteen ophthalmology journals with the highest impact factors that accepted original research. Descriptive statistics, one-way analysis of variance (ANOVA) tests, and negative binomial regression were used to compare citation counts based on author, study, and journal characteristics. In this study, author research productivity, journal impact factor, study funding, and location in high-income countries were predictors of increased citation in ophthalmology.},
}
@article {pmid36695800,
year = {2023},
author = {Takahashi, K and Song, Y and Cheong, KX and Fenner, BJ and Teo, KYC and Chee, ML and Li, H and Tham, YC and Cheung, CMG and Cheng, CY and Wong, TY and Yanagi, Y and Tan, ACS},
title = {PATTERN AND CHARACTERISTICS OF DRUSEN SUBTYPES IN CHINESE AND INDIAN POPULATIONS IN SINGAPORE.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {2},
pages = {303-312},
doi = {10.1097/IAE.0000000000003651},
pmid = {36695800},
issn = {1539-2864},
mesh = {Humans ; Aged ; Cohort Studies ; Cross-Sectional Studies ; Singapore/epidemiology ; *East Asian People ; Retrospective Studies ; *Retinal Drusen/diagnosis/epidemiology/etiology ; Tomography, Optical Coherence/methods ; Fluorescein Angiography ; },
abstract = {PURPOSE: To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness.<br><br>METHODS: This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness.<br><br>RESULTS: Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 &#x3bc;m; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 &#x3bc;m; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 &#x3bc;m; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 &#x3bc;m; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed.<br><br>CONCLUSION: Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.},
}
@article {pmid36695799,
year = {2023},
author = {Teo, KYC and Vyas, C and Sun, C and Cheong, KX and Chakravarthy, U},
title = {FIVE-YEAR INCIDENCE OF FELLOW EYE NEOVASCULAR INVOLVEMENT IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY IN AN ASIAN POPULATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {2},
pages = {294-302},
doi = {10.1097/IAE.0000000000003666},
pmid = {36695799},
issn = {1539-2864},
mesh = {Humans ; Incidence ; Polypoidal Choroidal Vasculopathy ; Prospective Studies ; Choroid/blood supply ; Fluorescein Angiography ; *Macular Degeneration/complications ; *Retinal Detachment/complications ; Tomography, Optical Coherence ; *Wet Macular Degeneration/complications/diagnosis/epidemiology ; Retrospective Studies ; *Choroidal Neovascularization/diagnosis/epidemiology/complications ; },
abstract = {PURPOSE: To assess 5-year cumulative incidence and risk factors of fellow eye involvement in Asian neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy.<br><br>METHODS: In a prospective cohort study of Asian nAMD and polypoidal choroidal vasculopathy, the fellow eyes were evaluated for exudation. The 5-year incidence of exudation was compared between nAMD and polypoidal choroidal vasculopathy.<br><br>RESULTS: A total of 488 patients were studied. The 5-year incidence of exudation in fellow eyes was 16.2% (95% confidence interval: 12.0-20.2). Polypoidal choroidal vasculopathy compared with nAMD in the first eye was associated with lower fellow eye progression (9.8% [95% confidence interval: 5.1-14.3]) vs. 22.9% [95% confidence interval: 15.8-29.3], P < 0.01). Drusen (hazards ratio 2.11 [95% confidence interval: 1.10-4.06]), shallow irregular retinal pigment epithelium elevation (2.86 [1.58-5.18]), and pigment epithelial detachment (3.01 [1.27-7.17]) were associated with greater progression. A combination of soft drusens and subretinal drusenoid deposits, and specific pigment epithelial detachment subtypes (multilobular, and sharp peaked) were associated with progression. Pigment epithelial detachment, shallow irregular retinal pigment epithelium elevation, and new subretinal hyperreflective material occurred at 10.4 &#xb1; 4.2 months, 11.1 &#xb1; 6.0 months, and 6.9 &#xb1; 4.3 months, respectively, before exudation.<br><br>CONCLUSION: The 5-year incidence of fellow eye involvement in Asian nAMD is lower than among Caucasians because of a higher polypoidal choroidal vasculopathy prevalence. Drusens, shallow irregular retinal pigment epithelium elevation, and pigment epithelial detachment are risk factors for fellow eye progression.},
}
@article {pmid36695798,
year = {2023},
author = {Kamei, T and Ooto, S and Uji, A and Ichioka, A and Tsujikawa, A},
title = {CHORIOCAPILLARIS STRUCTURE IN THE FELLOW EYES OF PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: An OCT Angiography Image Averaging Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {2},
pages = {286-293},
doi = {10.1097/IAE.0000000000003660},
pmid = {36695798},
issn = {1539-2864},
mesh = {Humans ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration/diagnosis ; Choroid/blood supply ; *Retinal Drusen/diagnosis ; },
abstract = {PURPOSE: Histological choriocapillaris abnormalities have been reported in age-related macular degeneration (AMD). Averaging multiple en face optical coherence tomography angiography improves the quality of imaging of the choriocapillaris. This study used multiple en face swept source optical coherence tomography angiography image averaging to examine the structural changes in the choriocapillaris in the fellow eyes of patients with neovascular AMD.<br><br>METHODS: All patients underwent macular optical coherence tomography angiography imaging. One eye per subject was repeatedly imaged, and nine raster scan sets were obtained. Registered en face images were averaged, and area of flow voids and number of flow voids were measured using ImageJ software.<br><br>RESULTS: Forty-eight patients with neovascular AMD were recruited for analysis. Twenty-seven patients had polypoidal choroidal vasculopathy, and 22 eyes had soft drusen. Twenty-six eyes of 26 healthy individuals were included as age-matched normal controls. The choriocapillaris had a meshwork appearance in all eyes. The mean flow void area of the choriocapillaris was larger in patients with AMD than normal controls (1.14 &#xb1; 0.16 mm2 vs. 1.01 &#xb1; 0.12 mm2, P = 0.002). The mean size of each flow void was greater in patients with AMD than normal controls (729 &#xb1; 210 &#xb5;m2 vs. 583 &#xb1; 120 &#xb5;m2, P = 0.003). The mean flow void area of the choriocapillaris was larger in eyes with soft drusen than without soft drusen (1.2 &#xb1; 0.2 mm2 vs. 1.1 &#xb1; 0.1 mm2, P = 0.024).<br><br>CONCLUSION: Multiple en face image averaging revealed precise choriocapillaris structures in the fellow eyes of patients with neovascular AMD.},
}
@article {pmid36693594,
year = {2023},
author = {Malmin, A and Thomseth, VM and Førland, PT and Khan, AZ and Hetland, HB and Chen, X and Haugen, IK and Utheim, TP and Forsaa, VA},
title = {Associations between Serial Intravitreal Injections and Dry Eye.},
journal = {Ophthalmology},
volume = {130},
number = {5},
pages = {509-515},
doi = {10.1016/j.ophtha.2023.01.009},
pmid = {36693594},
issn = {1549-4713},
mesh = {Humans ; Aged ; *Povidone-Iodine ; Retrospective Studies ; Intravitreal Injections ; *Dry Eye Syndromes/diagnosis/drug therapy/metabolism ; Meibomian Glands/metabolism ; Fluoresceins/metabolism ; Tears/metabolism ; },
abstract = {PURPOSE: To investigate the effects of serial intravitreal injections (IVIs) on the ocular surface and meibomian glands (MGs) in patients treated with anti-vascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD).<br><br>DESIGN: Retrospective, controlled, observational study.<br><br>PARTICIPANTS: Patients with nAMD receiving unilateral IVIs with anti-VEGF agents. The fellow eye was used as control.<br><br>METHODS: Tear film and ocular surface examinations were performed on a single occasion at a minimum of 4 weeks after IVI. A pre-IVI asepsis protocol with povidone-iodine (PVP-I) was applied.<br><br>MAIN OUTCOME MEASURES: Upper and lower MG loss, tear meniscus height (TMH), bulbar redness (BR) score, noninvasive tear break-up time (NIBUT), tear film osmolarity (TOsm), Schirmer test, corneal staining, fluorescein tear film break-up time (TBUT), meibomian gland expressibility (ME), and meibum quality.<br><br>RESULTS: Ninety patients with a mean age of 77.5&#x2009;years (standard deviation [SD], 8.4; range 54-95) were included. The median number of IVIs in treated eyes was 19.5 (range, 2-132). Mean MG loss in the upper eyelid was 19.1% (SD, 11.3) in treated eyes and 25.5% (SD, 14.6) in untreated fellow eyes (P&#xa0;= 0.001). For the lower eyelid, median MG loss was 17.4% (interquartile range [IQR], 9.4-29.9) in treated eyes and 24.5%&#x2009;(IQR, 14.2-35.2) in fellow eyes (P < 0.001). Mean BR was 1.32 (SD, 0.46) in treated eyes versus 1.44&#x2009;(SD, 0.45) in fellow eyes (P&#xa0;= 0.017). Median TMH was 0.36 mm (IQR, 0.28-0.52) in treated eyes and 0.32 mm (IQR, 0.24-0.49) in fellow eyes (P&#xa0;= 0.02). There were no differences between treated and fellow eyes regarding NIBUT, TOsm, Schirmer test, corneal staining, fluorescein TBUT, ME, or meibum quality.<br><br>CONCLUSIONS: Repeated IVIs with anti-VEGF with preoperative PVP-I application was associated with reduced MG loss, increased tear volume, and reduced signs of inflammation compared with fellow nontreated eyes in patients with nAMD. This regimen may thus have a beneficial effect on the ocular surface.<br><br>FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.},
}
@article {pmid36691224,
year = {2022},
author = {Ramos, PL and Santana, R and Marques, AP and Sousa, I and Rocha-Sousa, A and Macedo, AF},
title = {Cross-sectional study investigating the prevalence and causes of vision impairment in Northwest Portugal using capture-recapture.},
journal = {BMJ open},
volume = {12},
number = {9},
pages = {e056995},
pmid = {36691224},
issn = {2044-6055},
mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; Cross-Sectional Studies ; Prevalence ; Portugal ; Visual Acuity ; *Glaucoma ; Vision Disorders/etiology ; Blindness/complications ; *Persons with Visual Disabilities ; },
abstract = {OBJECTIVES: The aim of this study was to estimate the prevalence and causes of vision impairment (VI) in Portugal.<br><br>SETTING: Information about people with VI was obtained from primary care centres, blind association (ACAPO) and from hospitals (the PCVIP study) in the Northwest of Portugal during a period spanning years 2014-2015. Causes of VI were obtained from hospitals.<br><br>PARTICIPANTS: Administrative and medical records of people with visual acuity in the better seeing eye of 0.5 decimal (0.30logMAR) or worse and/or visual field less than 20&#xb0; were investigated. Capture-recapture with log-linear models was applied to estimate the number of individuals missing from lists of cases obtained from available sources.<br><br>Log-linear models were used to estimate the crude prevalence and the category specific prevalence of VI.<br><br>RESULTS: Crude prevalence of VI was 1.97% (95% CI 1.56% to 2.54%), and standardised prevalence was 1% (95% CI 0.78% to 1.27%). The age-specific prevalence was 3.27% (95% CI 2.36% to 4.90%), older than 64 years, 0.64% (95% CI 0.49% to 0.88%), aged 25-64 years, and 0.07% (95% CI 0.045% to 0.13%), aged less than 25 years. The female-to-male ratio was 1.3, that is, higher prevalence among females. The five leading causes of VI were diabetic retinopathy, cataract, age-related macular degeneration, glaucoma and disorders of the globe.<br><br>CONCLUSIONS: The prevalence of VI in Portugal was within the expected range and in line with other European countries. A significant number of cases of VI might be due to preventable cases and, therefore, a reduction of the prevalence of VI in Portugal seems possible. Women and old people were more likely to have VI and, therefore, these groups require extra attention. Future studies are necessary to characterise temporal changes in prevalence of VI in Portugal.},
}
@article {pmid36690666,
year = {2023},
author = {Choi, YA and Jeong, A and Woo, CH and Cha, SC and Park, DY and Sagong, M},
title = {Aqueous microRNA profiling in age-related macular degeneration and polypoidal choroidal vasculopathy by next-generation sequencing.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {1274},
pmid = {36690666},
issn = {2045-2322},
mesh = {Humans ; Choroid/pathology ; Polypoidal Choroidal Vasculopathy ; *MicroRNAs ; *Macular Degeneration/pathology ; High-Throughput Nucleotide Sequencing ; },
abstract = {Although many studies demonstrated the differences of clinical features, natural course, and response to treatment between typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), differential microRNAs (miRNAs) expression in the aqueous humor (AH) between them has not been reported yet. We investigated the roles of miRNAs in the AH of patients with typical AMD and PCV using next-generation sequencing (NGS) and quantitative PCR (qPCR). Target genes and predicted pathways of miRNAs were investigated via pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes database. A total of 161 miRNAs from eyes with typical AMD and 185 miRNAs from eyes with PCV were differentially expressed. 33 miRNAs were commonly upregulated, and 77 miRNAs were commonly downregulated in both typical AMD and PCV groups. Among them, hsa-miR-140-5p, hsa-miR-374c-3p, and hsa-miR-200a-5p were differentially expressed and were predicted to regulate proteoglycans in cancer, p53 signaling pathway, Hippo signaling pathway, and adherens junction. The differential expression profiles and target gene regulation networks of AH miRNAs may contribute to the development of different pathological phenotypes in typical AMD and PCV. The results of this study provide novel insights into the pathogenesis, associated prognostic biomarkers, and therapeutic targets in AMD and PCV.},
}
@article {pmid36690464,
year = {2023},
author = {Maeda, T and Takahashi, M},
title = {iPSC-RPE in Retinal Degeneration: Recent Advancements and Future Perspectives.},
journal = {Cold Spring Harbor perspectives in medicine},
volume = {13},
number = {8},
pages = {},
pmid = {36690464},
issn = {2157-1422},
mesh = {Humans ; *Retinal Degeneration/therapy ; *Induced Pluripotent Stem Cells ; *Macular Degeneration/therapy ; Retinal Pigment Epithelium ; Regenerative Medicine ; },
abstract = {Regenerative medicine is a great hope for patients suffering from diseases for which no effective treatment is available. With the creation of induced pluripotent stem cells (iPSCs) in 2006, research and development has accelerated expeditiously, reaching a practical stage worldwide. The iPSC-regenerative medicine in ophthalmology is one of the pioneers, which has kicked off clinical application ahead of other fields owing to its advantages. The clinical safety issues of iPSC-derived retinal pigment epithelial (iPSC-RPE) transplantation for exudative age-related macular degeneration have been addressed to a certain extent. Preparations are being made for the next clinical study based on the improvement of its therapeutic effects and expansion of indications globally. Steady progress toward the practical applications of regenerative medicine for the treatment of retinal disorders is expected in the future while strengthening global cooperation amid various research areas, clinical fields, and regulations.},
}
@article {pmid36690427,
year = {2023},
author = {Kuo, CY and Chung, MY and Chen, SJ},
title = {Pseudocoloboma-like maculopathy with biallelic RDH12 missense mutations.},
journal = {Journal of medical genetics},
volume = {60},
number = {9},
pages = {859-865},
pmid = {36690427},
issn = {1468-6244},
mesh = {Adult ; Adolescent ; Humans ; Male ; Female ; Young Adult ; Mutation, Missense/genetics ; Mutation ; DNA Mutational Analysis ; *Macular Degeneration/diagnosis/genetics ; *Retinal Diseases/diagnosis/genetics ; Atrophy ; Alcohol Oxidoreductases/genetics ; },
abstract = {BACKGROUND: Hereditary maculopathy is a group of clinically and genetically heterogeneous disorders. With distinctive clinical features, subtypes of macular atrophy may correlate with their genetic defects.<br><br>METHODS: Seven patients from six families with adolescent/adult-onset maculopathy were examined in this clinical case series. A detailed medical history and eye examination were performed. Genomic DNA sequencing was performed using whole exome sequencing or direct sequencing of retinol dehydrogenase 12 (RDH12) coding exons.<br><br>RESULTS: Seven patients, including one male and six female patients, with pseudocoloboma-like maculopathy had biallelic missense RDH12 mutations. The most common mutant allele found in six of the seven patients was p.Ala269Gly. The average disease onset was at age 19.3 years, and visual acuity ranged from count fingers to 1.0. Most of the patients had mild myopic refraction. Common findings on fundus examination and spectral-domain optical coherence tomography include discrete margins of pseudocoloboma-like macular lesions with variable degrees of chorioretinal atrophy, excavation of retinal tissue and pigmentary changes mainly in the macular area. The electroretinograms were relatively normal to subnormal in all participants.<br><br>CONCLUSIONS: Progressive macular degeneration with a relatively normal peripheral retina and subsequent development of a pseudocoloboma-like appearance were the main clinical features in patients with compound heterozygous RDH12 missense mutations. Genetic testing may be crucial for early diagnosis and may play a key role in the development of future treatment strategies.},
}
@article {pmid36690422,
year = {2024},
author = {Li, J and Dan, YS and Chua, SQ and Wong, QY and Chong, RS and Ang, M and , and Wong, CW and Hoang, QV and , },
title = {Pathologic myopia in highly myopic patients with high axial anisomyopia.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {3},
pages = {411-416},
doi = {10.1136/bjo-2022-322285},
pmid = {36690422},
issn = {1468-2079},
mesh = {Humans ; Middle Aged ; Aged ; Cross-Sectional Studies ; *Myopia, Degenerative/complications/diagnosis/epidemiology ; Refraction, Ocular ; Vision Disorders/pathology ; *Macular Degeneration/complications ; *Choroidal Neovascularization/pathology ; Tomography, Optical Coherence ; Axial Length, Eye/pathology ; },
abstract = {PURPOSE: To determine prevalence of anisomyopia (axial length (AL) difference ≥2.5 mm) among high myopes ((HMs), defined by spherical equivalent of ≤6.0 diopters or AL ≥ 26.5 mm). To characterise the shorter anisomyopic eye (SAE) and evaluate if pathologic myopia (PM) in the longer anisomyopic eye (LAE) was associated with increased risk of PM in the SAE.<br><br>METHODS: 1168 HMs were recruited from Singapore National Eye Centre clinic for this cross-sectional study. Biometry, fundus photography and swept-source optical coherence tomography were performed. Patients with high axial anisomyopia were identified. Structural characteristics and presence of PM were described. Stepwise multivariate regression explored associations between PM in the LAE and pathology in the SAE, controlling for confounding variables.<br><br>RESULTS: Prevalence of anisomyopia was 15.8% (184 of 1168 patients). Anisomyopic patients (age 65.8&#xb1;13.5 years) had mean AL of 30.6&#xb1;2.0&#x2009;mm and 26.2&#xb1;2.3&#x2009;mm in the LAE and SAE, respectively. 52.7% of SAEs had AL < 26.5&#x2009;mm. Prevalence of myopic macular degeneration, macula-involving posterior staphyloma (PS), myopic traction maculopathy (MTM) and myopic choroidal neovascularisation (mCNV) in the SAE was 52.2%, 36.5%, 13.0% and 8.2%, respectively. Macular hole in the LAE was associated with increased risk of MTM in the SAE (OR=4.88, p=0.01). mCNV in the LAE was associated with mCNV in the SAE (OR=3.57, p=0.02). PS in the LAE was associated with PS in the SAE (OR=4.03, p<0.001).<br><br>CONCLUSIONS: Even when controlled for AL, PM complications in the LAE predict similar PM complications in the SAE. Patients with high axial anisometropia with PM in the LAE should be monitored carefully for complications in the SAE.},
}
@article {pmid36690321,
year = {2023},
author = {Liu, H and Yan, J and Guan, F and Jin, Z and Xie, J and Wang, C and Liu, M and Liu, J},
title = {Zeaxanthin prevents ferroptosis by promoting mitochondrial function and inhibiting the p53 pathway in free fatty acid-induced HepG2 cells.},
journal = {Biochimica et biophysica acta. Molecular and cell biology of lipids},
volume = {1868},
number = {4},
pages = {159287},
doi = {10.1016/j.bbalip.2023.159287},
pmid = {36690321},
issn = {1879-2618},
mesh = {Humans ; Fatty Acids, Nonesterified/metabolism ; *Ferroptosis ; Hep G2 Cells ; Lipid Metabolism ; Mitochondria/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism ; Obesity/metabolism ; Tumor Suppressor Protein p53/metabolism ; Zeaxanthins/pharmacology/metabolism ; },
abstract = {Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder worldwide and a risk factor for obesity and diabetes. Emerging evidence has shown that ferroptosis is involved in the progression of NAFLD. Zeaxanthin (ZEA) is a carotenoid found in human serum. It has been reported that ZEA can ameliorate obesity, prevent age-related macular degeneration, and protect against non-alcoholic steatohepatitis. However, no study has focused on the protective effects of ZEA against NAFLD. In this study, free fatty acid (FFA) induced HepG2 cells were used as a cell model for NAFLD. Our results suggest that ZEA exerts antioxidative and anti-inflammatory effects in FFA-induced HepG2 cells. Moreover, ZEA acted as a ferroptosis inhibitor, significantly reducing reactive oxygen species (ROS) generation and iron overload and improving mitochondrial dysfunction in FFA-induced HepG2 cells. In addition, ZEA downregulated the expression of p53 and modulated downstream targets, such as GPX4, SLC7A11, SAT1, and ALOX15, which contributed to the reduction in cellular lipid peroxidation. Our findings suggest that ZEA has the potential for NAFLD intervention.},
}
@article {pmid36690073,
year = {2023},
author = {Wu, J and Chen, J and Hu, J and Yao, M and Zhang, M and Wan, X and Jia, H and Wang, F and Sun, X},
title = {CircRNA Uxs1/miR-335-5p/PGF axis regulates choroidal neovascularization via the mTOR/p70 S6k pathway.},
journal = {Translational research : the journal of laboratory and clinical medicine},
volume = {256},
number = {},
pages = {41-55},
doi = {10.1016/j.trsl.2023.01.003},
pmid = {36690073},
issn = {1878-1810},
mesh = {Aged ; Mice ; Animals ; Female ; Humans ; RNA, Circular/genetics/metabolism ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; Endothelial Cells/metabolism ; Angiogenesis Inhibitors/metabolism ; Vascular Endothelial Growth Factor A ; Placenta Growth Factor ; Visual Acuity ; *Wet Macular Degeneration/complications/metabolism ; *MicroRNAs/genetics/metabolism ; *Choroidal Neovascularization/genetics ; TOR Serine-Threonine Kinases/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Mammals/genetics/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the elderly population. Neovascular AMD is the late stage, characterized by choroidal neovascularization (CNV). Non-coding RNAs have been implicated in CNV; however, the role of circular RNAs (circRNAs) has not yet been elucidated. Herein, we comprehensively investigated circRNA profiles in laser-induced CNV mouse models and patient specimens. A novel circRNA, circRNA Uxs1, was identified, and its function in CNV regulation was investigated in the present study. CircRNA Uxs1 was consistently upregulated in CNV patient specimens and CNV mouse models. Knockdown of circRNA Uxs1 interrupted the tube formation, migration, and proliferation of endothelial cells in vitro. Silencing circRNA Uxs1 in vivo alleviated neovascularization formation, as shown by the decreased size of laser spots. Mechanistically, circRNA Uxs1 functioned by binding to miR-335-5p, which further upregulated the expression of placental growth factor (PGF) gene and activated the mammalian target of rapamycin/p70 S6 Kinase (mTOR/p70 S6k) pathway. By subretinal injections of adeno-associated virus (AAV), we demonstrated the anti-angiogenic function of circRNA Uxs1 knockdown in vivo. In conclusion, circRNA Uxs1 promoted CNV by sponging miR-335-5p, which stimulated PGF expression and subsequently activated the mTOR/p70 S6k pathway. Therefore, circRNA Uxs1 may serve as a promising therapeutic target for CNV.},
}
@article {pmid36689924,
year = {2023},
author = {Tian, H and Zhao, L and Li, H and Huang, Y and Wang, Y},
title = {Circular RNA in Retina: A Potential Biomarker and Therapeutic Target.},
journal = {Ophthalmic research},
volume = {66},
number = {1},
pages = {516-528},
doi = {10.1159/000529207},
pmid = {36689924},
issn = {1423-0259},
mesh = {Humans ; *RNA, Circular/genetics/metabolism ; RNA/genetics ; Retina/metabolism ; Biomarkers ; *Diabetic Retinopathy/diagnosis/genetics ; },
abstract = {Circular RNA (circRNA) is a newly discovered noncoding RNA, which forms a closed ring with more than 200 bases in length. CircRNA is formed by back splicing of precursor RNA, and its expression abundance in body fluid is up to 10 times that of homologous linear transcripts. Recently, novel activities for circRNA in various diseases have emerged, ranging from cancer therapy and neurodegenerative diseases. Here, we reviewed the literature on the biogenesis of circRNA and its relationship with retinal diseases in recent years. We first described the mechanism, existing form and main function of circRNA. Next, we also pinpoint that circRNA has great value in the diagnosis and treatment of retinal diseases represented by retinoblastoma, retinal degeneration, and diabetic retinopathy. By this review, we hope to explore more possibilities of circRNA in clinical diagnosis and treatment.},
}
@article {pmid36688155,
year = {2022},
author = {Decleva, D and Vidal, KS and Kreuz, AC and de Menezes, PAHL and Ventura, DF},
title = {Alterations of color vision and pupillary light responses in age-related macular degeneration.},
journal = {Frontiers in aging neuroscience},
volume = {14},
number = {},
pages = {933453},
pmid = {36688155},
issn = {1663-4365},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries and one of the leading causes of blindness. In this work, we evaluated color vision and the pupil light reflex (PLR) to assess visual function in patients with early and neovascular AMD (NVAMD) compared with the control group.<br><br>METHODS: We recruited 34 early patients with dry AMD and classified them into two groups following AREDS: 13 patients with NVAMD and 24 healthy controls. Controls and patients with early dry AMD had visual acuity (VA) best or equal to 20/25 (0.098 logMAR). Color vision was assessed in controls and patients with early dry AMD using the Cambridge Color Test (CCT) 2.0 through the Trivector protocol. The PLR was evaluated using a Ganzfeld, controlled by the RETI-port system. The stimuli consisted of 1s blue (470 nm) and red (631 nm) light flashes presented alternately at 2-min intervals. To assess the cone contribution, we used a red flash at 2.4 log cd.m[-2], with a blue background at 0.78 log cd.m[-2]. For rods, we used 470-nm flashes at -3 log cd.m[-2], and for the melanopsin function of ipRGCs, we used 470 nm at 2.4 log cd.m[-2].<br><br>RESULTS: Patients with early dry AMD had reduced color discrimination in all three axes: protan (p = 0.0087), deutan (p = 0.0180), and tritan (p = 0.0095) when compared with the control group. The PLR has also been affected in patients with early dry AMD and patients with NVAMD. The amplitude for the melanopsin-driven response was smaller in patients with early dry AMD (p = 0.0485) and NVAMD (p = 0.0035) than in the control group. The melanopsin function was lower in patients with NVAMD (p = 0.0290) than the control group. For the rod-driven response, the latency was lower in the NVAMD group (p = 0.0041) than in the control group. No changes were found in cone-driven responses between the control and AMD groups.<br><br>CONCLUSION: Patients with early dry AMD present diffusely acquired color vision alteration detected by CCT. Rods and melanopsin contributions for PLR are affected in NVAMD. The CCT and the PLR may be considered sensitive tests to evaluate and monitor functional changes in patients with AMD.},
}
@article {pmid36686279,
year = {2022},
author = {Moschetti, A and Fox, CA and McGowen, S and Ryan, RO},
title = {Lutein nanodisks protect human retinal pigment epithelial cells from UV light-induced damage.},
journal = {Frontiers in nanotechnology},
volume = {4},
number = {},
pages = {},
pmid = {36686279},
issn = {2673-3013},
support = {R01 HL064159/HL/NHLBI NIH HHS/United States ; R37 HL064159/HL/NHLBI NIH HHS/United States ; },
abstract = {The hydrophobic carotenoid, lutein, was conferred with aqueous solubility upon formulation into reconstituted discoidal high density lipoprotein particles, termed lutein nanodisks (ND). When formulated with phosphatidylcholine (PC), apolipoprotein (apo) A-I and lutein (formulation ratio = 5 mg PC/2 mg apoA-I/1 mg lutein), lutein solubilization efficiency in phosphate buffered saline (PBS) was ~90%. The UV/Vis absorbance maxima for lutein ND in PBS were red shifted by 6-13 nm versus the corresponding lutein absorbance maxima in ethanol. FPLC gel filtration chromatography gave rise to a single major absorbance peak in the size range of ND. Incubation of cultured ARPE-19 cells with lutein ND resulted in lutein uptake, as determined by HPLC analysis of cell extracts. Compared to control incubations, ARPE-19 cells incubated with lutein ND were protected from UV light-induced loss of cell viability. Consistent with this, reactive oxygen species generation, induced by exposure to UV irradiation, was lower in lutein-enriched cells than in control cells. Thus, uptake of ND-associated lutein protects ARPE-19 cells from UV light-induced damage. Taken together, the data indicate ND provide an aqueous lutein delivery vehicle for biotechnological or therapeutic applications.},
}
@article {pmid36683054,
year = {2023},
author = {Zhou, M and Li, DL and Kai, JY and Zhang, XF and Pan, CW},
title = {Sleep duration and the risk of major eye disorders: a systematic review and meta-analysis.},
journal = {Eye (London, England)},
volume = {37},
number = {13},
pages = {2707-2715},
pmid = {36683054},
issn = {1476-5454},
support = {82122059//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Sleep Duration ; Humans ; *Eye Diseases ; },
abstract = {BACKGROUND: To assess the relationship between sleep duration and the risk of major eye disorders including myopia, glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR).<br><br>METHODS: Databases including PubMed, Embase, Web of Science, and Cochrane library were searched for eligible publications before July 2021. Studies assessing the relationship between sleep duration and any one of the major eye disorders were identified. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were estimated using random-effects models.<br><br>RESULTS: We identified 21 relevant articles including 777348 participants, and 17 were cross-sectional, 3 were longitudinal, and 1 was case-control. Pooled results indicated that long sleep duration was significantly associated with the risk of DR (OR&#x2009;=&#x2009;1.84, 95% CI 1.24, 2.73), and short sleep duration was significantly associated with the risk of cataract (OR&#x2009;=&#x2009;1.20, 95% CI 1.05, 1.36). Besides, a significant relationship was observed between the risk of DR and long sleep duration per day (i.e., nighttime sleep plus daytime napping, OR&#x2009;=&#x2009;1.74, 95% CI 1.23, 2.44) rather than per night (OR&#x2009;=&#x2009;2.17, 95% CI 0.95, 4.99). The extreme of long sleep duration (i.e., >10&#x2009;h per night) increased the risk of myopia (OR&#x2009;=&#x2009;1.02, 95% CI 1.01, 1.04).<br><br>CONCLUSIONS: Inappropriate sleep duration might increase the risk of major eye disorders. The findings could contribute to the growing knowledge on the possible relationship between circadian rhythms and eye disorders.},
}
@article {pmid36681894,
year = {2023},
author = {Brash, DE and Goncalves, LCP},
title = {Chemiexcitation: Mammalian Photochemistry in the Dark[†].},
journal = {Photochemistry and photobiology},
volume = {99},
number = {2},
pages = {251-276},
pmid = {36681894},
issn = {1751-1097},
support = {P50 CA121974/CA/NCI NIH HHS/United States ; R01 AR070851/AR/NIAMS NIH HHS/United States ; },
mesh = {Animals ; *Melanins/chemistry ; Photochemistry ; *Pyrimidine Dimers ; Ultraviolet Rays ; Mammals ; },
abstract = {Light is one way to excite an electron in biology. Another is chemiexcitation, birthing a reaction product in an electronically excited state rather than exciting from the ground state. Chemiexcited molecules, as in bioluminescence, can release more energy than ATP. Excited states also allow bond rearrangements forbidden in ground states. Molecules with low-lying unoccupied orbitals, abundant in biology, are particularly susceptible. In mammals, chemiexcitation was discovered to transfer energy from excited melanin, neurotransmitters, or hormones to DNA, creating the lethal and carcinogenic cyclobutane pyrimidine dimer. That process was initiated by nitric oxide and superoxide, radicals triggered by ultraviolet light or inflammation. Several poorly understood chronic diseases share two properties: inflammation generates those radicals across the tissue, and cells that die are those containing melanin or neuromelanin. Chemiexcitation may therefore be a pathogenic event in noise- and drug-induced deafness, Parkinson's disease, and Alzheimer's; it may prevent macular degeneration early in life but turn pathogenic later. Beneficial evolutionary selection for excitable biomolecules may thus have conferred an Achilles heel. This review of recent findings on chemiexcitation in mammalian cells also describes the underlying physics, biochemistry, and potential pathogenesis, with the goal of making this interdisciplinary phenomenon accessible to researchers within each field.},
}
@article {pmid36681848,
year = {2023},
author = {Stolwijk, ML and van Nispen, RMA and van der Ham, AJ and Veenman, E and van Rens, GHMB},
title = {Barriers and facilitators in the referral pathways to low vision services from the perspective of patients and professionals: a qualitative study.},
journal = {BMC health services research},
volume = {23},
number = {1},
pages = {64},
pmid = {36681848},
issn = {1472-6963},
mesh = {Humans ; Aged ; *Vision, Low ; Qualitative Research ; Delivery of Health Care ; Health Personnel ; Referral and Consultation ; },
abstract = {BACKGROUND: Underutilization of and lack of access to low vision services (LVS) has been reported internationally. The purpose of this study was to identify barriers and facilitators in LVS referral procedures and service delivery from both the perspective of people with visual impairment and professionals from different eye care providers in the Netherlands.<br><br>METHODS: A qualitative study in the Netherlands was conducted. Barriers and facilitators were explored through semi structured interviews with older adults with macular degeneration, diabetic retinopathy and/or glaucoma (n&#x2009;=&#x2009;14), and healthcare professionals including ophthalmologists and LVS professionals (n&#x2009;=&#x2009;16). Framework analysis was used for analyzing the interviews with Atlas.ti software.<br><br>RESULTS: According to both patients and professionals, facilitators in LVS access and utilization are having motivation, self-advocacy, high participation needs and social support, as well as being negatively impacted by the impairment. Both samples found having good communication skills and informing patients about LVS as a healthcare provider to facilitate access. A long patient-provider relationship and the Dutch healthcare system were also mentioned as facilitators. Professionals additionally found long disease duration and the presence of low vision optometric services in the ophthalmic practice to promote access. Barriers that were reported by patients and professionals are lack of motivation, self-advocacy and acceptance of the impairment in patients. In addition, having low participation needs as a patient, lack of information provision by providers and time constraints in the ophthalmic practice were mentioned as barriers. Professionals also reported lack of social support, short disease duration of patients, a short patient-provider relationship and lack of coordination of care in the ophthalmic practice to hinder access.<br><br>CONCLUSIONS: Findings suggest that providers' lack of information provision about LVS, especially to patients who are less assertive, hamper referral to LVS. Providers should have attention for patients' LVS needs and actively inform them and their social network about LVS to facilitate access. Educating and training providers about how and when to address LVS may help to reduce barriers in the referral pathways. In addition, referral procedures may benefit from tools that make providers more aware of LVS.},
}
@article {pmid36680656,
year = {2023},
author = {Tao, T and Xu, H and Ma, X and Cheng, Y and Shi, X and Sun, Y and Zhao, M and Huang, L and Li, X},
title = {Analysis of Systemic and Serum Risk Factors in Patients with Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {2},
pages = {1033-1044},
pmid = {36680656},
issn = {2193-8245},
support = {81470649//National Natural Science Foundation of China/ ; 81670870//National Natural Science Foundation of China/ ; 2018-I2M-HL-019)//Science and Technology Innovation Project of Chinese Academy of Medical Sciences/ ; Z161100004916058//Beijing Nova Program/ ; 2017-C-001//Huaxia Translational Medicine Fund for Young Scholars/ ; 3502Z20189022//Xiamen Medical and Health Project/ ; },
abstract = {INTRODUCTION: It remains controversial whether polypoidal choroidal vasculopathy (PCV) represents a subtype of neovascular age-related macular degeneration (nAMD) or is a distinct disease entity. This study aimed to compare and analyze systemic and serum risk factors for nAMD and PCV in an aging Chinese population.<br><br>METHODS: A retrospective study was performed on 108 patients with nAMD, 131 patients with PCV, and 219 control subjects. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), complement 3 (C3), and complement 4 (C4) together with data on systemic risk factors, including hyperlipidemia, hypertension, diabetes mellitus (DM), coronary artery disease (CAD), and asthma, were collected. Chi-square tests, independent-samples t tests, and binary logistic regression analyses were performed to evaluate the associations of&#xa0;risk factors with nAMD and PCV.<br><br>RESULTS: Patients with PCV and those with nAMD were likely to have hyperlipidemia (P&#x2009;<&#x2009;0.001). CAD (P&#x2009;=&#x2009;0.020) and hypertension (P&#x2009;=&#x2009;0.006) correlated significantly with nAMD and PCV, respectively. Although no association of age and asthma with PCV or nAMD was found (P&#x2009;>&#x2009;0.05), DM was associated with PCV development (OR&#x2009;=&#x2009;0.535, P&#x2009;=&#x2009;0.044). Regarding serum risk factors, HDL, LDL, TG, APOB, and C3 were significantly associated with nAMD (OR&#x2009;<&#x2009;0.001, P&#x2009;<&#x2009;0.001; OR&#x2009;=&#x2009;0.028, P&#x2009;<&#x2009;0.001; OR&#x2009;=&#x2009;0.175, P&#x2009;<&#x2009;0.001; OR&#x2009;=&#x2009;0.922, P&#x2009;=&#x2009;0.022; OR&#x2009;<&#x2009;0.001, P&#x2009;<&#x2009;0.001) and PCV (OR&#x2009;=&#x2009;0.001, P&#x2009;=&#x2009;0.001; OR&#x2009;=&#x2009;0.097, P&#x2009;=&#x2009;0.003; OR&#x2009;=&#x2009;0.410, P&#x2009;=&#x2009;0.037; OR&#x2009;=&#x2009;0.895, P&#x2009;=&#x2009;0.001; OR&#x2009;=&#x2009;0.001, P&#x2009;<&#x2009;0.001). Compared with nAMD, higher levels of HDL (P&#x2009;=&#x2009;0.003) and LDL (P&#x2009;=&#x2009;0.016) and lower levels of TG (P&#x2009;=&#x2009;0.039) were found in patients with PCV, but the association of systemic risk factors between the two diseases was not significant&#xa0;(P&#x2009;>&#x2009;0.05).<br><br>CONCLUSION: Our findings indicate that hyperlipidemia is significantly associated with both nAMD and PCV. Serum lipid and complement levels have an effect on the pathogenesis of nAMD and PCV, and consideration of the differences between systemic and serum risk factors should be taken into account in clinical management.},
}
@article {pmid36678834,
year = {2023},
author = {Shastri, DH and Silva, AC and Almeida, H},
title = {Ocular Delivery of Therapeutic Proteins: A Review.},
journal = {Pharmaceutics},
volume = {15},
number = {1},
pages = {},
pmid = {36678834},
issn = {1999-4923},
abstract = {Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed.},
}
@article {pmid36678586,
year = {2023},
author = {Hara, C and Wakabayashi, T and Sayanagi, K and Nishida, K},
title = {Refractory Age-Related Macular Degeneration Due to Concurrent Central Serous Chorioretinopathy in Previously Well-Controlled Eyes.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {16},
number = {1},
pages = {},
pmid = {36678586},
issn = {1424-8247},
abstract = {Background: During the treatment of age-related macular degeneration with anti-vascular endothelial growth factor (VEGF) drugs, we often see cases with anti-VEGF-resistant refractory subretinal fluid. In this report, we present two cases of anti-VEGF-resistant refractory age-related macular degeneration (AMD) due to the concurrent development of central serous chorioretinopathy (CSCR) in eyes previously well controlled with intravitreal anti-VEGF injections. Case presentation: Two patients underwent intravitreal aflibercept for the treatment of neovascular AMD. Initially, both patients responded well to intravitreal aflibercept, resulting in the complete resolution of the subretinal fluid. However, both patients subsequently developed sudden-onset refractory subretinal fluid that did not respond to repeated intravitreal aflibercept. Fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography revealed focal leakage spots, choroidal hyperpermeability, and dilated choroidal vessels, respectively, which were distinct from the pre-existing choroidal neovascularization and suggestive of newly developed CSCR. Laser photocoagulation of the leak spots resulted in the complete resolution of the once-refractory subretinal fluid and the maintenance of vision. Conclusions: Our cases highlight that anti-VEGF-refractory subretinal fluid may occur secondary to concurrent CSCR in patients receiving regular anti-VEGF treatments for AMD. In those patients, treatment for CSCR is effective for controlling subretinal fluid that is unresolved by anti-VEGF treatment.},
}
@article {pmid36676762,
year = {2023},
author = {Zivkovic, M and Radosavljevic, A and Zlatanovic, M and Jaksic, V and Davidovic, S and Stamenkovic, M and Todorovic, I and Jaksic, J},
title = {Influence of Multiple Anti-VEGF Injections on Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness in Patients with Exudative Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {1},
pages = {},
pmid = {36676762},
issn = {1648-9144},
mesh = {Male ; Humans ; Female ; *Retinal Ganglion Cells ; Prospective Studies ; Nerve Fibers ; Retina ; Tomography, Optical Coherence/methods ; *Macular Degeneration/drug therapy ; },
abstract = {Backgrounds and Objectives: To analyze the influence of multiple anti-VEGF intravitreal injections for exudative age-related macular degeneration on the thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GC + IPL) using spectral domain optical coherence tomography (SD-OCT). Materials and Methods: A prospective interventional study of consecutive patients treated with intravitreal bevacizumab (IVB) was performed. Average and sectorial values of RNFL and GC + IPL thickness were recorded using Cirrus SD-OCT at 0, 6, 12, and 24 months. Patients suffering from any ocular disease that could affect RNFL or GC + IPL thickness were excluded. Results: A total of 135 patients (70 women and 65 men, aged 65 ± 15 years) were included. The average number of injections per patient was 12.4 ± 2.4. Average RNFL and GC + IPL thickness prior to the first injection (87.6 ± 12.2 and 47.2 ± 15.5 respectively), and after 24-month follow-up (86.2 ± 12.6 and 46.7 ± 11.9 respectively) did not differ significantly (p > 0.05). There was a significant decrease in GC2, GC5 segments, and minimum GC + IPL thickness. Conclusion: Repeated anti-VEGF treatment did not cause significant changes in the thickness of RNFL and GC + IPL layers over a period of 24 months. The detected decrease in GC2 and GC5 sectors, as well as in minimum GC + IPL thickness, could be a sign of ganglion cell damage induced by the treatment or could occur during the natural course of the disease.},
}
@article {pmid36676026,
year = {2022},
author = {Maiuolo, J and Bulotta, RM and Oppedisano, F and Bosco, F and Scarano, F and Nucera, S and Guarnieri, L and Ruga, S and Macri, R and Caminiti, R and Musolino, V and Gliozzi, M and Carresi, C and Cardamone, A and Coppoletta, A and Nicita, M and Carnevali, A and Scorcia, V and Mollace, V},
title = {Potential Properties of Natural Nutraceuticals and Antioxidants in Age-Related Eye Disorders.},
journal = {Life (Basel, Switzerland)},
volume = {13},
number = {1},
pages = {},
pmid = {36676026},
issn = {2075-1729},
abstract = {Eye health is crucial, and the onset of diseases can reduce vision and affect the quality of life of patients. The main causes of progressive and irreversible vision loss include various pathologies, such as cataracts, ocular atrophy, corneal opacity, age-related macular degeneration, uncorrected refractive error, posterior capsular opacification, uveitis, glaucoma, diabetic retinopathy, retinal detachment, undetermined disease and other disorders involving oxidative stress and inflammation. The eyes are constantly exposed to the external environment and, for this reason, must be protected from damage from the outside. Many drugs, including cortisonics and antinflammatory drugs have widely been used to counteract eye disorders. However, recent advances have been obtained via supplementation with natural antioxidants and nutraceuticals for patients. In particular, evidence has accumulated that polyphenols (mostly deriving from Citrus Bergamia) represent a reliable source of antioxidants able to counteract oxidative stress accompanying early stages of eye diseases. Luteolin in particular has been found to protect photoreceptors, thereby improving vision in many disease states. Moreover, a consistent anti-inflammatory response was found to occur when curcumin is used alone or in combination with other nutraceuticals. Additionally, Coenzyme Q10 has been demonstrated to produce a consistent effect in reducing ocular pressure, thereby leading to protection in patients undergoing glaucoma. Finally, both grape seed extract, rich in anthocyanosides, and polynsatured fatty acids seem to contribute to the prevention of retinal disorders. Thus, a combination of nutraceuticals and antioxidants may represent the right solution for a multi-action activity in eye protection, in association with current drug therapies, and this will be of potential interest in early stages of eye disorders.},
}
@article {pmid36675697,
year = {2022},
author = {Kalra, G and Cetin, H and Whitney, J and Yordi, S and Cakir, Y and McConville, C and Whitmore, V and Bonnay, M and Lunasco, L and Sassine, A and Borisiak, K and Cohen, D and Reese, J and Srivastava, SK and Ehlers, JP},
title = {Machine Learning-Based Automated Detection and Quantification of Geographic Atrophy and Hypertransmission Defects Using Spectral Domain Optical Coherence Tomography.},
journal = {Journal of personalized medicine},
volume = {13},
number = {1},
pages = {},
pmid = {36675697},
issn = {2075-4426},
support = {P30 EY025585/EY/NEI NIH HHS/United States ; K23-EY022947-01A1/EY/NEI NIH HHS/United States ; },
abstract = {The current study describes the development and assessment of innovative, machine learning (ML)-based approaches for automated detection and pixel-accurate measurements of regions with geographic atrophy (GA) in late-stage age-related macular degeneration (AMD) using optical coherence tomography systems. 900 OCT volumes, 100266 B-scans, and en face OCT images from 341 non-exudative AMD patients with or without GA were included in this study from both Cirrus (Zeiss) and Spectralis (Heidelberg) OCT systems. B-scan and en face level ground truth GA masks were created on OCT B-scan where the segmented ellipsoid zone (EZ) line, retinal pigment epithelium (RPE) line, and bruchs membrane (BM) line overlapped. Two deep learning-based approaches, B-scan level and en face level, were trained. The OCT B-scan model had detection accuracy of 91% and GA area measurement accuracy of 94%. The en face OCT model had detection accuracy of 82% and GA area measurement accuracy of 96% with primary target of hypertransmission on en face OCT. Accuracy was good for both devices tested (92-97%). Automated lesion size stratification for CAM cRORA definition of 250um minimum lesion size was feasible. High-performance models for automatic detection and segmentation of GA area were achieved using OCT systems and deep learning. The automatic measurements showed high correlation with the ground truth. The en face model excelled at identification of hypertransmission defects. The models performance generalized well across device types tested. Future development will include integration of both models to enhance feature detection across GA lesions as well as isolating hypertransmission defects without GA for pre-GA biomarker extraction.},
}
@article {pmid36675451,
year = {2023},
author = {Mathis, T and El Ameen, B and Chaperon, M and Serrar, Y and Devin, F and Dziadzko, M and Rezkallah, A and Kodjikian, L},
title = {Relevance of Visual Acuity Measurement for Therapeutic Decisions in Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {12},
number = {2},
pages = {},
pmid = {36675451},
issn = {2077-0383},
abstract = {The aim of this study is to assess if the decision to retreat could be determined by anatomical criteria (mostly driven by optical coherence tomography (OCT)-guided strategy) rather than the gold standard (visual acuity (VA) and OCT) in patients with neovascular age-related macular degeneration (nAMD). A cross-sectional study of 142 eyes already treated for nAMD from September 2021 to December 2021 was performed. At inclusion, a first therapeutic decision was made based on the analysis of the OCT. This decision was then maintained or modified after being made aware of the patient's VA. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. The OCT-guided strategy matched the gold standard for treatment decisions in 131 of the 142 eyes included (92.3%). The sensitivity and specificity of the OCT-guided strategy for the retreatment decision were 94.0% and 89.8%, respectively. PPV and NPV were 92.9% and 91.4%, respectively. Considering the treatment regimen, eyes followed under the Pro ReNata regimen showed better sensitivity (100%) and specificity (93.3%) than eyes followed under the treat and extend regimen (93.5% and 88.6%, respectively). Based on the findings of this study, the follow-up for selected patients with nAMD under anti-VEGF treatment could be monitored without regular VA testing with acceptable performance.},
}
@article {pmid36675446,
year = {2023},
author = {Toro, MD and Vidal-Aroca, F and Montemagni, M and Xompero, C and Fioretto, G and Costagliola, C},
title = {Three-Month Safety and Efficacy Outcomes for the Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT™).},
journal = {Journal of clinical medicine},
volume = {12},
number = {2},
pages = {},
pmid = {36675446},
issn = {2077-0383},
abstract = {The smaller-incision new-generation implantable miniature telescope (SING IMT™) is the second generation of the IMT™, a telescope prosthesis that is indicated for monocular implantation in patients with stable vision impairment caused by bilateral central scotomas associated with end-stage Age-related macular degeneration (AMD). This non-comparative retrospective study is the first and largest single-surgeon case series to evaluate the short-term (3 months) safety and efficacy of the device in patients with disciform scars or geographic atrophy at baseline. The main outcome measures included best-corrected distance and near visual acuity (CDVA and CDNVA, respectively), endothelial cell density (ECD) loss, and the incidence of complications. At postoperative month 3 in the study eyes, mean CDVA and CDNVA improved by +14.9 ± 7.1 letters and +7.7 ± 3.2 Jaeger levels, respectively. Importantly, 70.83% of patients gained ≥ 2 lines, 58.33% ≥ 3 lines, and 25.00% ≥ 4 lines of CDVA. From baseline, ECD loss in the study eyes was 10.4 ± 13.3% at 3 months, however, ECD was comparable between the study and fellow eyes at all time points. The most common complication was corneal edema. In all, these short-term outcomes suggest that the SING IMT™ delivers lower ECD loss than the first-generation IMT ™, but similar visual outcomes and safety.},
}
@article {pmid36675261,
year = {2023},
author = {Taylor, BE and Lee, CA and Zapadka, TE and Zhou, AY and Barber, KG and Taylor, ZRR and Howell, SJ and Taylor, PR},
title = {IL-17A Enhances Retinal Neovascularization.},
journal = {International journal of molecular sciences},
volume = {24},
number = {2},
pages = {},
pmid = {36675261},
issn = {1422-0067},
support = {I01 CX002204/CX/CSRD VA/United States ; P30 EY011373/EY/NEI NIH HHS/United States ; R01 EY030487/EY/NEI NIH HHS/United States ; 2020-22//Cleveland Eye Bank Foundation/ ; },
mesh = {Mice ; Animals ; *Retinal Neovascularization/metabolism ; *Diabetic Retinopathy/pathology ; Vascular Endothelial Growth Factor A/metabolism ; *Diabetes Mellitus, Experimental/metabolism ; Endothelial Cells/metabolism ; Interleukin-17/genetics/metabolism ; Retina/metabolism ; },
abstract = {Retinal neovascularization occurs in proliferative diabetic retinopathy, neovascular glaucoma, and age-related macular degeneration. This type of retinal pathology normally occurs in the later stages of these ocular diseases and is a prevalent cause of vision loss. Previously, we determined that Interleukin (IL)-17A plays a pivotal role in the onset and progression of non-proliferative diabetic retinopathy in diabetic mice. Unfortunately, none of our diabetic murine models progress to proliferative diabetic retinopathy. Hence, the role of IL-17A in vascular angiogenesis, neovascularization, and the onset of proliferative diabetic retinopathy was unclear. In the current study, we determined that diabetes-mediated IL-17A enhances vascular endothelial growth factor (VEGF) production in the retina, Muller glia, and retinal endothelial cells. Further, we determined that IL-17A can initiate retinal endothelial cell proliferation and can enhance VEGF-dependent vascular angiogenesis. Finally, by utilizing the oxygen induced retinopathy model, we determined that IL-17A enhances retinal neovascularization. Collectively, the results of this study provide evidence that IL-17A plays a pivotal role in vascular proliferation in the retina. Hence, IL-17A could be a potentially novel therapeutic target for retinal neovascularization, which can cause blindness in multiple ocular diseases.},
}
@article {pmid36675091,
year = {2023},
author = {Liu, Y and Wu, D and Fu, Q and Hao, S and Gu, Y and Zhao, W and Chen, S and Sheng, F and Xu, Y and Chen, Z and Yao, K},
title = {CHAC1 as a Novel Contributor of Ferroptosis in Retinal Pigment Epithelial Cells with Oxidative Damage.},
journal = {International journal of molecular sciences},
volume = {24},
number = {2},
pages = {},
pmid = {36675091},
issn = {1422-0067},
support = {491020+N2211FZJ to Ye Liu and Y23H120038 to Zhiqing Chen//Zhejiang Provincial Natural Science Foundation of China/ ; },
mesh = {Aged ; Humans ; Epithelial Cells/metabolism ; *Ferroptosis/genetics/physiology ; Glutathione/metabolism ; *Macular Degeneration/metabolism ; *Oxidative Stress/genetics/physiology ; *Retinal Pigment Epithelium/metabolism ; Retinal Pigments/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. With aging and the accumulated effects of environmental stress, retinal pigment epithelial (RPE) cells are particularly susceptible to oxidative damage, which can lead to retinal degeneration. However, the underlying molecular mechanisms of how RPE responds and progresses under oxidative damage are still largely unknown. Here, we reveal that exogenous oxidative stress led to ferroptosis characterized by Fe[2+] accumulation and lipid peroxidation in RPE cells. Glutathione specific gamma-glutamylcyclotransferase 1 (Chac1), as a component of the unfolded protein response (UPR) pathway, plays a pivotal role in oxidative-stress-induced cell ferroptosis via the regulation of glutathione depletion. These results indicate the biological significance of Chac1 as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.},
}
@article {pmid36674587,
year = {2023},
author = {Samra, YA and Zaidi, Y and Rajpurohit, P and Raghavan, R and Cai, L and Kaddour-Djebbar, I and Tawfik, A},
title = {Warburg Effect as a Novel Mechanism for Homocysteine-Induced Features of Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {24},
number = {2},
pages = {},
pmid = {36674587},
issn = {1422-0067},
support = {R01 EY029751-01-NEI00072/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Animals ; Cells, Cultured ; *Macular Degeneration/metabolism ; Retinal Pigment Epithelium/metabolism ; *Hyperhomocysteinemia/metabolism ; *Choroidal Neovascularization/metabolism ; Cystathionine beta-Synthase/metabolism ; Homocysteine/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of blindness. Recent studies have reported impaired glycolysis in AMD patients with a high lactate/pyruvate ratio. Elevated homocysteine (Hcy) (Hyperhomocysteinemia, HHcy) was observed in several clinical studies, reporting an association between HHcy and AMD. We established the effect of HHcy on barrier function, retinal pigment epithelium (RPE) structure, and induced choroidal neovascularization (CNV) in mice. We hypothesize that HHcy contributes to AMD by inducing a metabolic switch in the mitochondria, in which cells predominantly produce energy by the high rate of glycolysis, or "Warburg", effect. Increased glycolysis results in an increased production of lactate, cellular acidity, activation of angiogenesis, RPE barrier dysfunction, and CNV. Evaluation of cellular energy production under HHcy was assessed by seahorse analysis, immunofluorescence, and western blot experiments. The seahorse analysis evaluated the extracellular acidification rate (ECAR) as indicative of glycolysis. HHcy showed a significant increase in ECAR both in vivo using (Cystathionine β-synthase) cbs[+/-] and cbs[-/-] mice retinas and in vitro (Hcy-treated ARPE-19) compared to wild-type mice and RPE cells. Moreover, HHcy up-regulated glycolytic enzyme (Glucose transporter-1 (GlUT-1), lactate dehydrogenase (LDH), and hexokinase 1 (HK1)) in Hcy-treated ARPE-19 and primary RPE cells isolated from cbs[+/+], cbs[+/-], and cbs[-/-] mice retinas. Inhibition of GLUT-1 or blocking of N-methyl-D-aspartate receptors (NMDAR) reduced glycolysis in Hcy-treated RPE and improved albumin leakage and CNV induction in Hcy-injected mice eyes. The current study suggests that HHcy causes a metabolic switch in the RPE cells from mitochondrial respiration to glycolysis during AMD and confirms the involvement of NMDAR in this process. Therefore, targeting Glycolysis or NMDAR could be a novel therapeutic target for AMD.},
}
@article {pmid36674579,
year = {2023},
author = {Di Staso, F and Di Pippo, M and Abdolrahimzadeh, S},
title = {Choroidal Neovascular Membranes in Retinal and Choroidal Tumors: Origins, Mechanisms, and Effects.},
journal = {International journal of molecular sciences},
volume = {24},
number = {2},
pages = {},
pmid = {36674579},
issn = {1422-0067},
mesh = {Humans ; *Choroid Neoplasms/pathology ; Vascular Endothelial Growth Factor A/metabolism ; *Macular Degeneration/metabolism ; *Choroidal Neovascularization/pathology ; Retina/metabolism ; Choroid/metabolism ; *Retinal Neovascularization/metabolism ; *Melanoma/metabolism ; *Osteoma/complications/metabolism/pathology ; },
abstract = {Choroidal neovascularizations are historically associated with exudative macular degeneration, nonetheless, they have been observed in nevus, melanoma, osteoma, and hemangioma involving the choroid and retina. This review aimed to elucidate the possible origins of neovascular membranes by examining in vivo and in vitro models compared to real clinical cases. Among the several potential mechanisms examined, particular attention was paid to histologic alterations and molecular cascades. Physical or biochemical resistance to vascular invasion from the choroid offered by Bruch's membrane, the role of fibroblast growth factor 2 and vascular endothelial growth factor, resident or recruited stem-like/progenitor cells, and other angiogenic promoters were taken into account. Even if the exact mechanisms are still partially obscure, experimental models are progressively enhancing our understanding of neovascularization etiology. Choroidal neovascularization (CNV) over melanoma, osteoma, and other tumors is not rare and is not contraindicative of malignancy as previously believed. In addition, CNV may represent a late complication of either benign or malignant choroidal tumors, stressing the importance of a long follow-up.},
}
@article {pmid36673042,
year = {2023},
author = {Zhang, L and Van Dijk, EHC and Borrelli, E and Fragiotta, S and Breazzano, MP},
title = {OCT and OCT Angiography Update: Clinical Application to Age-Related Macular Degeneration, Central Serous Chorioretinopathy, Macular Telangiectasia, and Diabetic Retinopathy.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {36673042},
issn = {2075-4418},
abstract = {Similar to ultrasound adapting soundwaves to depict the inner structures and tissues, optical coherence tomography (OCT) utilizes low coherence light waves to assess characteristics in the eye. Compared to the previous gold standard diagnostic imaging fluorescein angiography, OCT is a noninvasive imaging modality that generates images of ocular tissues at a rapid speed. Two commonly used iterations of OCT include spectral-domain (SD) and swept-source (SS). Each comes with different wavelengths and tissue penetration capacities. OCT angiography (OCTA) is a functional extension of the OCT. It generates a large number of pixels to capture the tissue and underlying blood flow. This allows OCTA to measure ischemia and demarcation of the vasculature in a wide range of conditions. This review focused on the study of four commonly encountered diseases involving the retina including age-related macular degeneration (AMD), diabetic retinopathy (DR), central serous chorioretinopathy (CSC), and macular telangiectasia (MacTel). Modern imaging techniques including SD-OCT, TD-OCT, SS-OCT, and OCTA assist with understanding the disease pathogenesis and natural history of disease progression, in addition to routine diagnosis and management in the clinical setting. Finally, this review compares each imaging technique's limitations and potential refinements.},
}
@article {pmid36672999,
year = {2023},
author = {Kaothanthong, N and Limwattanayingyong, J and Silpa-Archa, S and Tadarati, M and Amphornphruet, A and Singhanetr, P and Lalitwongsa, P and Chantangphol, P and Amornpetchsathaporn, A and Chainakul, M and Ruamviboonsuk, P},
title = {The Classification of Common Macular Diseases Using Deep Learning on Optical Coherence Tomography Images with and without Prior Automated Segmentation.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {36672999},
issn = {2075-4418},
abstract = {We compared the performance of deep learning (DL) in the classification of optical coherence tomography (OCT) images of macular diseases between automated classification alone and in combination with automated segmentation. OCT images were collected from patients with neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, retinal vein occlusion, cystoid macular edema in Irvine-Gass syndrome, and other macular diseases, along with the normal fellow eyes. A total of 14,327 OCT images were used to train DL models. Three experiments were conducted: classification alone (CA), use of automated segmentation of the OCT images by RelayNet, and the graph-cut technique before the classification (combination method 1 (CM1) and 2 (CM2), respectively). For validation of classification of the macular diseases, the sensitivity, specificity, and accuracy of CA were found at 62.55%, 95.16%, and 93.14%, respectively, whereas the sensitivity, specificity, and accuracy of CM1 were found at 72.90%, 96.20%, and 93.92%, respectively, and of CM2 at 71.36%, 96.42%, and 94.80%, respectively. The accuracy of CM2 was statistically higher than that of CA (p = 0.05878). All three methods achieved AUC at 97%. Applying DL for segmentation of OCT images prior to classification of the images by another DL model may improve the performance of the classification.},
}
@article {pmid36672232,
year = {2023},
author = {Subirada, PV and Tovo, A and Vaglienti, MV and Luna Pinto, JD and Saragovi, HU and Sánchez, MC and Anastasía, A and Barcelona, PF},
title = {Etiological Roles of p75[NTR] in a Mouse Model of Wet Age-Related Macular Degeneration.},
journal = {Cells},
volume = {12},
number = {2},
pages = {},
pmid = {36672232},
issn = {2073-4409},
mesh = {Mice ; Animals ; *Wet Macular Degeneration/metabolism ; Retina/metabolism ; Receptor, Nerve Growth Factor/genetics ; *Choroidal Neovascularization/metabolism ; Mice, Knockout ; Disease Models, Animal ; },
abstract = {Choroidal neovascularization (CNV) is a pathological angiogenesis of the choroidal plexus of the retina and is a key feature in the wet form of age-related macular degeneration. Mononuclear phagocytic cells (MPCs) are known to accumulate in the subretinal space, generating a chronic inflammatory state that promotes the growth of the choroidal neovasculature. However, how the MPCs are recruited and activated to promote CNV pathology is not fully understood. Using genetic and pharmacological tools in a mouse model of laser-induced CNV, we demonstrate a role for the p75 neurotrophin receptor (p75[NTR]) in the recruitment of MPCs, in glial activation, and in vascular alterations. After laser injury, expression of p75[NTR] is increased in activated Muller glial cells near the CNV area in the retina and the retinal pigmented epithelium (RPE)-choroid. In p75[NTR] knockout mice (p75[NTR] KO) with CNV, there is significantly reduced recruitment of MPCs, reduced glial activation, reduced CNV area, and the retinal function is preserved, as compared to wild type mice with CNV. Notably, a single intravitreal injection of a pharmacological p75[NTR] antagonist in wild type mice with CNV phenocopied the results of the p75[NTR] KO mice. Our results demonstrate that p75[NTR] is etiological in the development of CNV.},
}
@article {pmid36671003,
year = {2023},
author = {Sekar, P and Hsiao, G and Chen, YS and Lin, WW and Chan, CM},
title = {P2X7 Is Involved in the Mouse Retinal Degeneration via the Coordinated Actions in Different Retinal Cell Types.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {1},
pages = {},
pmid = {36671003},
issn = {2076-3921},
support = {MOST 110-2314-B-567 - 003 - MY3; NSCCMOH-145-61//Ministry of Science and Technology, Taiwan/ ; NTUHYL109.S010//National Taiwan University/ ; },
abstract = {Adenosine triphosphate (ATP) released from dying cells with high concentrations is sensed as a danger signal by the P2X7 receptor. Sodium iodate (NaIO3) is an oxidative toxic agent, and its retinal toxicity has been used as the model of dry age-related macular degeneration (AMD). In this study, we used NaIO3-treated mice and cultured retinal cells, including BV-2 microglia, 661W photoreceptors, rMC1 Müller cells and ARPE-19 retinal epithelial cells, to understand the pathological action of P2X7 in retinal degeneration. We found that NaIO3 can significantly decrease the photoreceptor function by reducing a-wave and b-wave amplitudes in electroretinogram (ERG) analysis. Optical coherence tomography (OCT) analysis revealed the degeneration of retinal epithelium and ganglion cell layers. Interestingly, P2X7[-/-] mice were protected from the NaIO3-induced retinopathy and inflammatory NLRP3, IL-1β and IL-6 gene expression in the retina. Hematoxylin and eosin staining indicated that the retinal epithelium was less deteriorated in P2X7[-/-] mice compared to the WT group. Although P2X7 was barely detected in 661W, rMC1 and ARPE-19 cells, its gene and protein levels can be increased after NaIO3 treatment, leading to a synergistic cytotoxicity of BzATP [2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate tri(triethyleneammonium)salt] and NaIO3 administration in ARPE-19 cells. In conclusion, the paracrine action of the ATP/P2X7 axis via cell-cell communication is involved in NaIO3-induced retinal injury. Our results show that P2X7 antagonist might be a potential therapy in inflammation-related retinal degeneration.},
}
@article {pmid36670906,
year = {2022},
author = {Shimizu, H and Takayama, K and Yamada, K and Suzumura, A and Sato, T and Nishio, Y and Ito, M and Ushida, H and Nishiguchi, KM and Takeuchi, M and Kaneko, H},
title = {Dimethyl Fumarate Protects Retinal Pigment Epithelium from Blue Light-Induced Oxidative Damage via the Nrf2 Pathway.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {1},
pages = {},
pmid = {36670906},
issn = {2076-3921},
support = {19K09988, 22K09810, 21K16912, 22K16949, 22K16968//Grants-in-Aid for Scientific Research (C) and Grants-in-Aid for Young Scientific from JSPS KAKENHI, Takeda Science Foundation and The Naito Foundation./ ; },
abstract = {The purpose of this study is to investigate the protective effect of dimethyl fumarate (DMF), the methyl-ester of fumaric acid, against blue-light (BL) exposure in retinal pigment epithelial (RPE) cells. ARPE-19 cells, a human RPE cell line, were cultured with DMF followed by exposure to BL. Reactive oxygen species (ROS) generation, cell viability, and cell death rate were determined. Real-time polymerase chain reaction and Western blotting were performed to determine the change in nuclear factor (erythroid-derived)-like 2 (NRF2) expression. Twenty-seven inflammatory cytokines in the supernatant of culture medium were measured. BL exposure induced ROS generation in ARPE-19 cells, which DMF alleviated in a concentration-dependent manner. BL exposure increased the ARPE-19 cell death rate, which DMF alleviated. BL exposure induced ARPE-19 cell apoptosis, again alleviated by DMF. Under BL exposure, DMF increased the NRF2 mRNA level and promoted NRF2 expression in the nucleus. BL also strongly increased interleukin (IL)-1β and fibroblast growth factor (FGF) expression. BL strongly induced RPE cell damage with apoptotic change while DMF mainly reduced inflammation in BL-induced RPE damage, resulting in blockade of cell death. DMF has a protective effect in RPE cells against BL exposure via activation of the NRF2 pathway.},
}
@article {pmid36670299,
year = {2023},
author = {Rosner, B and Bay, C and Glynn, RJ and Ying, GS and Maguire, MG and Lee, MT},
title = {Estimation and testing for clustered interval-censored bivariate survival data with application using the semi-parametric version of the Clayton-Oakes model.},
journal = {Lifetime data analysis},
volume = {29},
number = {4},
pages = {854-887},
pmid = {36670299},
issn = {1572-9249},
support = {P30 EY001583/EY/NEI NIH HHS/United States ; R01 EY022445/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Proportional Hazards Models ; Survival Analysis ; Computer Simulation ; Likelihood Functions ; *Diabetic Retinopathy ; },
abstract = {The Kaplan-Meier estimator is ubiquitously used to estimate survival probabilities for time-to-event data. It is nonparametric, and thus does not require specification of a survival distribution, but it does assume that the risk set at any time t consists of independent observations. This assumption does not hold for data from paired organ systems such as occur in ophthalmology (eyes) or otolaryngology (ears), or for other types of clustered data. In this article, we estimate marginal survival probabilities in the setting of clustered data, and provide confidence limits for these estimates with intra-cluster correlation accounted for by an interval-censored version of the Clayton-Oakes model. We develop a goodness-of-fit test for general bivariate interval-censored data and apply it to the proposed interval-censored version of the Clayton-Oakes model. We also propose a likelihood ratio test for the comparison of survival distributions between two groups in the setting of clustered data under the assumption of a constant between-group hazard ratio. This methodology can be used both for balanced and unbalanced cluster sizes, and also when the cluster size is informative. We compare our test to the ordinary log rank test and the Lin-Wei (LW) test based on the marginal Cox proportional Hazards model with robust standard errors obtained from the sandwich estimator. Simulation results indicate that the ordinary log rank test over-inflates type I error, while the proposed unconditional likelihood ratio test has appropriate type I error and higher power than the LW test. The method is demonstrated in real examples from the Sorbinil Retinopathy Trial, and the Age-Related Macular Degeneration Study. Raw data from these two trials are provided.},
}
@article {pmid36670145,
year = {2023},
author = {Baba, T and Koyama, A and Uotani, R and Miyake, H and Inata, K and Sasaki, SI and Shimizu, Y and Inoue, Y and Adachi, K and Nanba, E and Miyazaki, D},
title = {Association of IL-4 with pachychoroid neovasculopathy.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {1152},
pmid = {36670145},
issn = {2045-2322},
mesh = {Humans ; Choroid/blood supply ; *Choroidal Neovascularization/pathology ; Cytokines ; Fluorescein Angiography ; Interleukin-2 ; *Interleukin-4 ; Retrospective Studies ; Tomography, Optical Coherence ; },
abstract = {The purpose of this study was to identify the inflammatory cytokines that were associated with pachychoroid neovasculopathy (PNV). Seventy-five eyes of 75 patients with PNV, 145 eyes of 145 patients with neovascular age-related macular degeneration without pachyvessels, and 150 eyes of 150 normal subjects were examined for the levels of intraocular cytokines. In eyes with PNV, the levels of IL-1α, IL-1β, IL-2, IL-4, IL-10, and VEGF were significantly higher than that of the controls. Logistic regression analysis showed that the highest association with the pachyvessels was found for IL-4, IL-2, and IL-1α. In eyes with PNV, the levels of IL-4, IL-2, IL-5, IL-13, IL-1α, and IL-1β were significantly higher in eyes with both increased choroidal thickness and choroidal vessel diameter. The strongest correlation with the choroidal thickness and vessel diameter was observed for IL-4. In PNV eyes with polypoidal lesions, the levels of IL-4, IL-17, and TNFβ were significantly correlated with the number of polypoidal lesions. Of these cytokines, IL-4 was especially associated with the thickness of the choroidal vessels and the formation of polypoidal lesions. We conclude that IL-4 is most likely involved in establishing the clinical characteristics of PNV and polypoidal vascular remodeling.},
}
@article {pmid36669130,
year = {2023},
author = {Fang, HS and Bai, CH and Cheng, CK},
title = {STRICT PRO RE NATA VERSUS TREAT-AND-EXTEND REGIMENS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A SYSTEMATIC REVIEW AND META-ANALYSIS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {3},
pages = {420-432},
doi = {10.1097/IAE.0000000000003690},
pmid = {36669130},
issn = {1539-2864},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Treatment Outcome ; Intravitreal Injections ; Tomography, Optical Coherence ; Visual Acuity ; Retrospective Studies ; *Macular Degeneration/drug therapy ; *Wet Macular Degeneration/drug therapy ; },
abstract = {PURPOSE: To compare the visual and anatomical outcomes between strict pro re nata (strict PRN) and treat-and-extend (T&amp;E) anti-vascular endothelial growth factor (anti-VEGF) regimens for neovascular age-related macular degeneration (nAMD).<br><br>METHODS: A meta-analysis of 1-year and 2-year changes between strict PRN and T&amp;E anti-VEGF regimens were conducted in both randomized controlled trials (RCTs) and real-world studies (RWSs). The best-corrected visual acuity (BCVA), central retinal thickness (CRT), and weighted mean numbers of visits and injections were evaluated.<br><br>RESULTS: A total of 19 RCTs and 23 RWSs (2,530 eyes in strict PRN and 4,399 eyes in T&amp;E) were included. Mean BCVA change in strict PRN group in both 1-year and 2-year (5.95 and 5.78, respectively) was noninferior to the T&amp;E group (7.85 and 5.96, respectively). Mean CRT changes were also similar in both strict PRN and T&amp;E groups. Mean number of visits were significantly more in the strict PRN group, whereas mean number of injections was significantly more in the T&amp;E group.<br><br>CONCLUSION: The strict PRN regimen demonstrates a noninferior BCVA improvement to the T&amp;E regimen, achieving fewer injections, and may be both economically and medically beneficial. Both selections should be provided to patients with an overall consideration.},
}
@article {pmid36662498,
year = {2023},
author = {Tanaya, T and Swain, TA and Clark, ME and Swanner, JC and Lolley, VR and Callahan, MA and McGwin, G and Owsley, C},
title = {Comparing Rod-Mediated Dark Adaptation in Older Adults before and after Cataract Surgery.},
journal = {Current eye research},
volume = {48},
number = {5},
pages = {512-517},
pmid = {36662498},
issn = {1460-2202},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY029595/EY/NEI NIH HHS/United States ; T35 HL007473/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Aged ; Dark Adaptation ; *Cataract Extraction ; *Capsule Opacification ; Visual Acuity ; *Cataract/complications ; },
abstract = {PURPOSE: Studies on age-related macular degeneration often use rod-mediated dark adaptation (RMDA) to evaluate macular functional health, studying eyes with cataract and pseudophakic eyes within the same sample. We examine a poorly understood issue-whether rod intercept time (RIT), a measure of RMDA, changes after cataract surgery and intraocular lens (IOL) insertion as compared to RIT before cataract surgery. Cataract may serve as a filter reducing photo-bleach magnitude prior to surgery, biasing RMDA interpretation.<br><br>METHODS: A pre-/post-cataract surgery design was used. Persons with nuclear sclerotic and/or cortical cataract per the electronic health record were enrolled. Prior to cataract surgery, visual acuity, RMDA, and the LOCS III classification documenting cataract presence/severity were measured. Thirty days after surgery (mean), visual acuity and RMDA were repeated, followed by fundus photos to document macular health.<br><br>RESULTS: Twenty-four participants (mean age 72.7&#x2009;years, standard deviation 5.6) enrolled. All eyes had nuclear sclerotic and nuclear color cataract; 68% had cortical cataract. All IOLs were monofocal with 21 having blue blocking characteristics and 3 had clear IOLs. Most eyes had higher RIT post-surgery (15.6&#x2009;min, SD 6.7) as compared to pre-surgery (13.7&#x2009;min, SD 6.4), p&#x2009;=&#x2009;0.0006, meaning that RMDA was slower post-surgery. Eyes with moderate cataract (<4 on any LOCS III grade) had RIT that increased on average by 0.7&#x2009;min; those with more advanced cataract (&#x2265;4) had RIT that increased by 3.1&#x2009;min (p&#x2009;=&#x2009;0.0116). Results were unchanged when clear IOLs were removed from analysis.<br><br>CONCLUSION: RMDA was significantly slower (RIT was greater) following cataract surgery, with the greatest impact on RIT in older eyes after surgery for more advanced cataract. These findings suggest that persons with more advanced cataract may bias results when evaluating RMDA using RIT.},
}
@article {pmid36661792,
year = {2022},
author = {Liu, M and Huang, Y and Tao, C and Yang, W and Chen, J and Zhu, L and Pan, T and Narain, R and Nan, K and Chen, Y},
title = {Self-Healing Alginate Hydrogel Formed by Dynamic Benzoxaborolate Chemistry Protects Retinal Pigment Epithelium Cells against Oxidative Damage.},
journal = {Gels (Basel, Switzerland)},
volume = {9},
number = {1},
pages = {},
pmid = {36661792},
issn = {2310-2861},
support = {LQ20E030010//Natural Science Foundation of Zhejiang Province/ ; 52003199//National Natural Science Foundation of China/ ; 2016YFC1101201//National Key R&amp;D Program of China/ ; Y20180230//Fundamental Research Project of Wenzhou Bureau of Science and Technology/ ; KYYW201916//Research Fund from Wenzhou Medical University/ ; KYQD20190515//Research Fund from Wenzhou Medical University/ ; Y202147886//Scientific Research Fund of Zhejiang Provincial Education Department/ ; },
abstract = {Oxidative stress is considered as a major factor causing retinal pigment epithelium (RPE) dysfunction and finally leading to retinal diseases such as age-related macular degeneration (AMD). Developing hydrogels for RPE cell delivery, especially those with antioxidant feature, is emerging as a promising approach for AMD treatment. Herein, a readily prepared antioxidant alginate-based hydrogel was developed to serve as a cytoprotective agent for RPE cells against oxidative damage. Alg-BOB was synthesized via conjugation of benzoxaborole (BOB) to the polysaccharide backbone. Hydrogels were formed through self-crosslinking of Alg-BOB based on benzoxaborole-diol complexation. The resulting hydrogel showed porous micro-structure, pH dependent mechanical strength and excellent self-healing, remolding, and injectable properties. Moreover, the hydrogel exhibited excellent cytocompatibility and could efficiently scavenge reactive oxygen species (ROS) to achieve an enhanced viability of ARPE-19 cells under oxidative condition. Altogether, our study reveals that the antioxidant Alg-BOB hydrogel represents an eligible candidate for RPE delivery and AMD treatment.},
}
@article {pmid36660787,
year = {2023},
author = {Che, JB and Wang, JM and Gao, J and Han, WH and Zhang, JB},
title = {[Relationship between expression of NLRP3 inflammasome and improvement of macular structure in patients with wet age-related macular degeneration after anti-vascular endothelial growth factor therapy].},
journal = {Zhonghua yi xue za zhi},
volume = {103},
number = {4},
pages = {265-270},
doi = {10.3760/cma.j.cn112137-20220823-01792},
pmid = {36660787},
issn = {0376-2491},
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Caspase 1/metabolism ; *Inflammasomes/metabolism ; Interleukin-18 ; Interleukin-1beta/metabolism ; *Macular Degeneration/drug therapy/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; RNA, Messenger ; Tumor Necrosis Factor-alpha/metabolism ; *Vascular Endothelial Growth Factor A/antagonists &amp; inhibitors ; },
abstract = {Objective: To explore the relationship between expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and improvement of macular structure in patients with wet age-related macular degeneration (wAMD) after anti-vascular endothelial growth factor (VEGF) therapy. Methods: A before-after study was carried out. A total of 110 patients (110 eyes) with wAMD who were admitted to Department of Ophthalmology, People's Hospital Affiliated to Shandong First Medical University between August 2019 and December 2021 were enrolled, and all patients were given vitreous injection of anti-VEGF drug (ranibizumab or bevacizumab). The aqueous humor was collected to detect mRNA levels of NLRP3, cysteinyl aspartate specific protease-1 (Caspase-1), apoptosis-associated speck-like protein (ASC) and interleukin (IL) 1β by fluorescence quantitative PCR. The levels of IL-1β, IL-18, tumor necrosis factor α (TNF-α) and VEGF in aqueous humor were detected by enzyme-linked immunosorbent assay (ELISA). The correlation between the above indexes and central macular thickness (CMT) in wAMD patients was analyzed by multivariate linear regression analysis. Results: In the 110 wAMD patients, there were 68 males and 42 females, with a mean age of (68.7±7.6) years. Compared with those before treatment, mRNA levels of NLRP3 (1.65±0.27, 1.34±0.19 vs 1.97±0.23, both P<0.017), Caspase-1 (1.47±0.15, 1.29±0.17 vs 1.53±0.18, both P<0.017), ASC (1.33±0.14, 1.21±0.18 vs 1.47±0.12, both P<0.017) and IL-1β (1.78±0.21, 1.46±0.17 vs 2.21±0.24, both P<0.017), and levels of IL-1β [(26.9±5.7), (20.3±4.6) vs (33.6±8.3) ng/L, both P<0.017], IL-18 [(32.7±7.6), (23.3±6.9) vs (46.4±9.4) ng/L, both P<0.017], TNF-α [(39.4±6.6), (21.7±6.3) vs (52.9±9.1) ng/L, both P<0.017] and VEGF [(35.7±10.2), (23.4±6.7) vs (65.4±19.3) ng/L, both P<0.017] were decreased after the first and second injection. Moreover, the above-mentioned indexes after second injection were lower than those after the first injection (all P<0.017). The results of multivariate linear regression analysis showed that NLRP3 mRNA (the first injection: β=53.750, P<0.001; the second injection: β=94.648, P<0.001), IL-1β (the first injection: β=1.356, P=0.021; the second injection: β=2.008, P=0.003), IL-18 (the first injection: β=1.984, P<0.001; the second injection: β=1.251, P=0.003) and VEGF (the first injection: β=1.875, P<0.001; the second injection: β=2.119, P<0.001) had linear relationships with CMT. Conclusion: The decrease of NLRP3 inflammasome and its products in aqueous humor may be related to the improvement of macular structure in wAMD patients after anti-VEGF therapy.},
}
@article {pmid36660699,
year = {2022},
author = {Chen, J and Li, Q},
title = {A retrospective analysis on comparison of optical coherence tomography manifestations among AMD, CEC, PM and ICN and its relationship with vision.},
journal = {Annals of translational medicine},
volume = {10},
number = {24},
pages = {1358},
pmid = {36660699},
issn = {2305-5839},
abstract = {BACKGROUND: Both macular choroidal neovascularization (MCN) and visual changes can occur in age-related macular degeneration (AMD), central exudative chorioretinopathy (CEC), pathological myopia (PM) and idiopathic choroidal neovascularization (ICN), but whether the optical coherence tomography (OCT) manifestations of the four diseases are different and their relationships with vision are not clear. This study clarifies this problem and can guide clinicians to prevent vision changes of patients according to OCT performance.<br><br>METHODS: 76 patients with MCN, included 25 AMD, 21 CEC, 18 PM and 12 ICN [refer to Chinese Ophthalmology (3rd Edition)], detected by OCT instrument, were enrolled in this study from June 2020 to June 2022. The OCT manifestations and indexes were observed. A comprehensive refractometer was used for detection of best corrected visual acuity (BCVA) and axial length (AL). Pearson chi squared and 1 way analysis of variance were used for enumeration data and continuous data test, and Pearson correlation coefficient was used for relationship analysis.<br><br>RESULTS: (I) Macular edema proportions in the MCN eyes among AMD, CEC, PM and ICN groups were 96.00% and 94.12%, 14.29% and 14.29%, 44.44% and 32.00%, 33.33% and 28.57%, with statistical differences (both P<0.001). (II) Patients with macular edema had a significantly higher loose and thickened tissue reflex of the neuroepithelial layer (100.00% vs. 4.26%) and limited non-reflective dark area (100.00% vs. 4.26%) (both P<0.001). (III) PM had the lowest width, height and central fovea thickness (CFT) [(1,403.43&#xb1;114.41), (210.74&#xb1;21.22) and (250.70&#xb1;41.36) &#x3bc;m], and the highest distance to the fovea, BCVA and AL [(234.44&#xb1;288.69) &#x3bc;m, (0.30&#xb1;0.08) Log minimal angle of resolution (MAR), (28.48&#xb1;5.72) mm] (all P<0.001). (IV) The width and height of patients with macular edema were lower than those of patients without macular edema [(1,738.43&#xb1;348.71) vs. (2,493.95&#xb1;771.53) &#x3bc;m, P<0.001; (305.71&#xb1;81.22) vs. (367.29&#xb1;107.91) &#x3bc;m, P=0.002] (P<0.05). (V) The width and height, CFT were negatively correlated to BCVA (r=-0.635, -0.712, -0.724, all P<0.001), and height, CFT were negatively correlated to AL (r=-0.244, -0.275, P=0.018, 0.007). The distance to the fovea was positively correlated to BCVA and AL (r=0.241, P=0.019; r=0.267, P=0.007).<br><br>CONCLUSIONS: Most of the OCT indexes were related to the BCVA and AL in MCN patients, and MCN patients with OCT changes should be reminded to protect their vision.},
}
@article {pmid36660308,
year = {2023},
author = {Chandrasekaran, PR and Aziz, AA and Khan, H and Khanani, AM},
title = {Cooling Anesthesia for Intravitreal Injections - A Review.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {197-207},
pmid = {36660308},
issn = {1177-5467},
abstract = {Intravitreal (IVT) injections are the most common procedure performed in retinal clinics today. It has revolutionized the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular edema, macular edema due to veinous occlusive disease and other forms of exudative maculopathy. Though IVT injections prevent vision loss, the discomfort at the time of the injection has been troublesome to patients. This has led to patients missing their regular and routine dosage of treatment. Various modes of pre-injection anesthetic methods have been tried but in vain. Lidocaine-based topical anesthesia, in the form of pledgets, topical gel or subconjunctival lidocaine injection, has been the standard of care (SOC) for IVT injections worldwide. This article highlights the role of cooling anesthesia in reducing pain, anxiety and discomfort associated with needle penetration at the time of injection. PubMed and MedLine search were related to anesthesia for intravitreal injections, cooling anesthesia, mechanism of cooling anesthesia, COOL-1 trial, COOL-2 trial, results of COOL-1 trial and ultrarapid cooling anesthesia.},
}
@article {pmid36660124,
year = {2022},
author = {Acharya, S and Kharel Sitaula, R and Karki, P and Mishra, SK and Dahal, HN and Poudel, A},
title = {Does outer retinal layer thickness correlate with the central visual field indices in early dry age-related macular degeneration?.},
journal = {Taiwan journal of ophthalmology},
volume = {12},
number = {4},
pages = {437-443},
pmid = {36660124},
issn = {2211-5072},
abstract = {PURPOSE: Age-related macular degeneration (ARMD) is the leading cause of irreversible blindness worldwide and Nepal is one among them. We aimed to determine the relationship between outer retinal layer thickness parameters with central visual field indices in early dry ARMD cases among Nepalese population.<br><br>MATERIALS AND METHODS: The subjects for this descriptive, cross-sectional study comprised 40 patients with early dry ARMD from the ophthalmology department of a tertiary level hospital of Nepal. The retinal layer thickness was measured with spectral-domain optical coherence tomography (SD-OCT), and the visual field indices were assessed using the 10-2 protocol of Humphrey visual field analyzer (HFA). Thus, the retinal layer structures correlated with visual field indices among our population.<br><br>RESULTS: Among our early dry ARMD population, the foveal threshold (FT) was found to be significantly correlated with retinal pigment epithelium (RPE) elevation (P < 0.01, r = -0.541), outer segment (OS) length (P = 0.02, r = 0.465), and inner segment ellipsoid (ISe) band disruption (P = 0.01, r = -0.499), but not with presence of hyperreflective foci (P = 0.464), RPE thickness (P = 0.612), and central macular thickness (P = 0.214). However, no significant correlation between mean deviation and pattern standard deviation of visual field with retinal layer thickness parameters was identified.<br><br>CONCLUSION: In early dry ARMD, a reduced FT is significantly correlated with the integrity of the ISe band, thinning of OS length, and drusen-associated RPE elevation. The results highlight the utility of both SD-OCT retinal layer measurement and central visual field testing by HFA in ARMD to monitor the progression of the disease.},
}
@article {pmid36657167,
year = {2023},
author = {Machida, A and Oishi, A and Tsuiki, E and Maekawa, Y and Kurihara, J and Hirata, Y and Machida, E and Kitaoka, T},
title = {INVESTIGATION OF INCIDENCE AND CAUSES OF ACUTE VISION LOSS DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DURING A FOUR-YEAR FOLLOW-UP.},
journal = {Retina (Philadelphia, Pa.)},
volume = {43},
number = {6},
pages = {888-896},
doi = {10.1097/IAE.0000000000003740},
pmid = {36657167},
issn = {1539-2864},
mesh = {Humans ; Child, Preschool ; Angiogenesis Inhibitors/adverse effects ; Endothelial Growth Factors ; Vascular Endothelial Growth Factor A ; Follow-Up Studies ; Incidence ; Retrospective Studies ; Retinal Pigment Epithelium ; *Macular Degeneration/drug therapy ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/chemically induced ; Ranibizumab/adverse effects ; },
abstract = {PURPOSE: To investigate the incidence, risk factors, and outcomes of patients with age-related macular degeneration who experienced acute vision loss despite periodic injections of anti-vascular endothelial growth factor treatment for 4 years.<br><br>METHODS: This retrospective cohort study included patients who were diagnosed with treatment-naive neovascular age-related macular degeneration and completed a 4-year follow-up. The incidence and risk factors for the occurrence of three or more lines of visual loss at every checkup were investigated.<br><br>RESULTS: The analysis included 76 eyes of 76 patients. Acute vision loss occurred in 30 eyes (39.5%) over 4 years. Lower baseline best-corrected visual acuity and disrupted ellipsoid zone were independent predictors of vision loss occurrence. Although the causes and timing of visual acuity loss varied, retinal pigment epithelium tears were observed only in the first year. Most patients (86.7%) who experienced vision loss recovered their vision to pre-loss levels at least once; however, the final best-corrected visual acuity was worse than that in the group that did not experience acute vision loss.<br><br>CONCLUSION: Approximately half of the patients with age-related macular degeneration experienced acute vision loss during a 4-year follow-up, despite continuous anti-vascular endothelial growth factor treatment. Most patients recovered from vision losses temporarily; however, they experienced worse visual outcomes subsequently.},
}
@article {pmid36656604,
year = {2022},
author = {Lee, J and Wanyan, T and Chen, Q and Keenan, TDL and Glicksberg, BS and Chew, EY and Lu, Z and Wang, F and Peng, Y},
title = {Predicting Age-related Macular Degeneration Progression with Longitudinal Fundus Images Using Deep Learning.},
journal = {Machine learning in medical imaging. MLMI (Workshop)},
volume = {13583},
number = {},
pages = {11-20},
pmid = {36656604},
support = {R00 LM013001/LM/NLM NIH HHS/United States ; },
abstract = {Accurately predicting a patient's risk of progressing to late age-related macular degeneration (AMD) is difficult but crucial for personalized medicine. While existing risk prediction models for progression to late AMD are useful for triaging patients, none utilizes longitudinal color fundus photographs (CFPs) in a patient's history to estimate the risk of late AMD in a given subsequent time interval. In this work, we seek to evaluate how deep neural networks capture the sequential information in longitudinal CFPs and improve the prediction of 2-year and 5-year risk of progression to late AMD. Specifically, we proposed two deep learning models, CNN-LSTM and CNN-Transformer, which use a Long-Short Term Memory (LSTM) and a Transformer, respectively with convolutional neural networks (CNN), to capture the sequential information in longitudinal CFPs. We evaluated our models in comparison to baselines on the Age-Related Eye Disease Study, one of the largest longitudinal AMD cohorts with CFPs. The proposed models outperformed the baseline models that utilized only single-visit CFPs to predict the risk of late AMD (0.879 vs 0.868 in AUC for 2-year prediction, and 0.879 vs 0.862 for 5-year prediction). Further experiments showed that utilizing longitudinal CFPs over a longer time period was helpful for deep learning models to predict the risk of late AMD. We made the source code available at https://github.com/bionlplab/AMD_prognosis_mlmi2022 to catalyze future works that seek to develop deep learning models for late AMD prediction.},
}
@article {pmid36656567,
year = {2023},
author = {Biles, MK and Maniglia, M and Yadav, IS and Vice, JE and Visscher, KM},
title = {Training With Simulated Scotoma Leads to Behavioral Improvements Through at Least Two Distinct Mechanisms.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {64},
number = {1},
pages = {14},
pmid = {36656567},
issn = {1552-5783},
support = {P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY031589/EY/NEI NIH HHS/United States ; U01 EY025858/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Scotoma ; Retina ; *Retinal Diseases ; *Macular Degeneration ; Vision Disorders ; Fixation, Ocular ; },
abstract = {PURPOSE: Individuals with central vision loss due to macular degeneration (MD) often spontaneously develop a preferred retinal locus (PRL) outside the area of retinal damage, which they use instead of the fovea. Those who develop a stable PRL are more successful at coping with their vision loss. However, it is unclear whether improvements in visual performance at the PRL are specific to that retinal location or are also observed in other parts of the retina. Perceptual learning literature suggests that the retinal specificity of these effects provides insight about the mechanisms involved. Better understanding of these mechanisms is necessary for the next generation of interventions and improved patient outcomes.<br><br>METHODS: To address this, we trained participants with healthy vision to develop a trained retinal locus (TRL), analogous to the PRL in patients. We trained 24 participants on a visual search task using a gaze-contingent display to simulate a central scotoma.<br><br>RESULTS: Results showed retinotopically specific improvements in visual crowding only at the TRL; however, visual acuity improved in both the TRL and in an untrained retinal locus.<br><br>CONCLUSIONS: These results suggest that training with an artificial scotoma involves multiple mechanistic levels, some location-specific and some not, and that simulated scotoma training paradigms likely influence multiple mechanisms simultaneously. Eye movement analysis suggests that the non-retinotopic learning effects may be related to improvements in the capability to maintain a stable gaze during stimulus presentation. This work suggests that effective interventions promoting peripheral viewing may influence multiple mechanisms simultaneously.},
}
@article {pmid36653641,
year = {2023},
author = {Krishnan, V and Meehan, SD and Hayter, C and Bhattacharya, SK},
title = {Analyses and Localization of Phosphatidylcholine and Phosphatidylserine in Murine Ocular Tissue Using Imaging Mass Spectrometry.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2625},
number = {},
pages = {149-161},
pmid = {36653641},
issn = {1940-6029},
mesh = {Mice ; Animals ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; *Phosphatidylcholines ; *Phosphatidylserines ; Lipidomics ; Specimen Handling ; },
abstract = {Imaging mass spectrometry (IMS) allows for spatial visualization of proteins, lipids, and metabolite distributions in a tissue. Identifying these compounds through mass spectrometry, combined with mapping the compound distribution in the sample in a targeted or untargeted approach, renders IMS a powerful tool for lipidomics. IMS analysis for lipid species such as phosphatidylcholine and phosphatidylserine allows researchers to pinpoint areas of lipid deficiencies or accumulations associated with ocular disorders such as age-related macular degeneration and diabetic retinopathy. Here, we describe an end-to-end IMS approach from sample preparation to data analysis for phosphatidylcholine and phosphatidylserine analysis.},
}
@article {pmid36653633,
year = {2023},
author = {Kumar, S and Joshi, MB and Kaur, I},
title = {Protocol and Methods Applicable to Retinal Vascular Diseases.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2625},
number = {},
pages = {71-78},
pmid = {36653633},
issn = {1940-6029},
mesh = {Infant, Newborn ; Humans ; Lipids/chemistry ; *Retinal Diseases ; Tandem Mass Spectrometry/methods ; Retina/chemistry ; *Diabetic Retinopathy ; },
abstract = {Lipidomics is a branch of omics biology that enables the characterization and determination of different lipid classes. Mass spectrometry is a widely used tool to identify and obtain qualitative and quantitative measurements of the range of lipid species in various cell/tissue types. Human retina is highly rich in different classes of lipids that are liable to undergo modification such as oxidation, isomerization, peroxidation, and hydroxylation due to continuous metabolic activity in response to light photons. Alterations in lipid metabolism are associated with retinal diseases such as age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. However, a clear understanding on the type of lipids/alterations involved in these diseases is not established yet. The unavailability of suitable biological retinal tissue need for this research has prompted us to explore vitreous humor and tear film for studying lipidomic alterations in different ocular diseases. Subjecting the lipid extract to tandem mass spectrometry further gives qualitative and quantitative lipidome of the diseased tissue. While the mass spectrometry approaches for lipid profiling have been adequately described, the present chapter focusses on a simplified protocol for extracting sufficient lipids/metabolites from vitreous humor and tear samples obtained from patients and their subsequent mass spectrometry analysis.},
}
@article {pmid36652737,
year = {2023},
author = {Sun, M and Yu, T and Zhao, J and Zhu, X and Xin, W and Zhang, F and Zhang, L},
title = {Role of flavonoids in age-related macular degeneration.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {159},
number = {},
pages = {114259},
doi = {10.1016/j.biopha.2023.114259},
pmid = {36652737},
issn = {1950-6007},
mesh = {Humans ; *Flavonoids/pharmacology/therapeutic use ; *Macular Degeneration/drug therapy ; Eye ; Neovascularization, Pathologic ; Inflammation/complications ; },
abstract = {A common eye disorder known as age-related macular degeneration (AMD) eventually results in blindness and vision loss. AMD has a complicated and poorly understood aetiology. The main pathological processes associated with AMD include oxidative damage, inflammation, and neovascularization. Flavonoids are naturally occurring bioactive substances with extensive distribution and antioxidant, anti-inflammatory, and neovascularization inhibitory properties. Several in vitro and in vivo AMD-related models pertinent to vision and this ocular ailment have been used to assess the mechanisms of action of various flavonoids. This article will discuss the research progress of flavonoids in AMD, especially the characteristics and mechanism of flavonoids in treating AMD.},
}
@article {pmid36651217,
year = {2023},
author = {Pruimboom-Brees, IM and Gupta, S and Chemuturi, N and Booler, HS and Nimz, E and Ferrell Ramos, M and Caruso, A and Maass, KF and Bantseev, V and Huang, Q and Choules, MP and Nussbaum, JC and Kanodia, J and Thompson, C and Durairaj, C},
title = {International consortium for innovation and quality: An industry perspective on the nonclinical and early clinical development of intravitreal drugs.},
journal = {Clinical and translational science},
volume = {16},
number = {5},
pages = {723-741},
pmid = {36651217},
issn = {1752-8062},
mesh = {Humans ; *Macular Edema/drug therapy ; *Diabetic Retinopathy/drug therapy ; Pharmaceutical Preparations ; Intravitreal Injections ; },
abstract = {The eye, which is under constant exposure to environmental pathogens, has evolved various anatomic and immunological barriers critical to the protection of tissues lacking regenerative capacity, and the maintenance of a clear optic pathway essential to vision. By bypassing the ocular barriers, intravitreal (IVT) injection has become the mainstay for the delivery of drugs to treat conditions that affect the back of the eye. Both small molecules and biotherapeutics have been successfully administered intravitreally, and several drugs have been approved for the treatment of (wet) age-related macular degeneration and diabetic macular edema. However, IVT injection is an invasive procedure, which requires sufficient technical expertise from the healthcare professional administering the drug. Potential side effects include bleeding, retinal tear, cataracts, infection, uveitis, loss of vision, and increased ocular pressure. Pharmaceutical companies often differ in their drug development plan, including drug administration techniques, collection of ocular tissues and fluids, ophthalmology monitoring, and overall conduct of nonclinical and clinical studies. The present effort, under the aegis of the Innovation &amp; Quality Ophthalmic Working Group, aims at understanding these differences, identifying pros and cons of the various approaches, determining the gaps in knowledge, and suggesting feasible good practices for nonclinical and early clinical IVT drug development.},
}
@article {pmid36650100,
year = {2023},
author = {Szeto, SK and Hui, VWK and Siu, V and Mohamed, S and Chan, CKM and Cheung, CYL and Hsieh, YT and Tan, CS and Chhablani, J and Lai, TYY and Ng, DS},
title = {Recent Advances in Clinical Applications of Imaging in Retinal Diseases.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {2},
pages = {252-263},
doi = {10.1097/APO.0000000000000584},
pmid = {36650100},
issn = {2162-0989},
mesh = {Humans ; *Diabetic Retinopathy ; *Macular Edema/diagnostic imaging ; Fluorescein Angiography/methods ; *Retinal Diseases/diagnosis ; *Central Serous Chorioretinopathy/diagnosis ; Retina ; Tomography, Optical Coherence/methods ; },
abstract = {Many diseases that cause visual impairment, as well as systemic conditions, manifest in the posterior segment of the eye. With the advent of high-speed, high-resolution, reliable, and noninvasive imaging techniques, ophthalmologists are becoming more dependent on ocular imaging for disease diagnosis, classification, and management in clinical practice. There are rapid advances on the indications of multimodal retinal imaging techniques, including the application of ultra-widefield fundus angiography, fundus autofluorescence, optical coherence tomography, as well as optical coherence tomography angiography. This review summarizes and highlights the clinical applications, latest indications, and interpretations of multimodal imaging in age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, central serous chorioretinopathy, diabetic retinopathy, retinal vein occlusion, and uveitis.},
}
@article {pmid36650098,
year = {2023},
author = {Arrigo, A and Aragona, E and Bandello, F},
title = {The Role of Inflammation in Age-Related Macular Degeneration: Updates and Possible Therapeutic Approaches.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {12},
number = {2},
pages = {158-167},
doi = {10.1097/APO.0000000000000570},
pmid = {36650098},
issn = {2162-0989},
mesh = {Humans ; *Macular Degeneration/diagnosis/etiology/therapy ; Retina/pathology ; Inflammation/metabolism ; },
abstract = {Age-related macular degeneration (AMD) is a common retinal disease characterized by complex pathogenesis and extremely heterogeneous characteristics. Both in "dry" and "wet" AMD forms, the inflammation has a central role to promote the degenerative process and to stimulate the onset of complications. AMD is characterized by several proinflammatory stimuli, cells and mediators involved, and metabolic pathways. Nowadays, inflammatory biomarkers may be unveiled and analyzed by means of several techniques, including laboratory approaches, histology, immunohistochemistry, and noninvasive multimodal retinal imaging. These methodologies allowed to perform remarkable steps forward for understanding the role of inflammation in AMD pathogenesis, also offering new opportunities to optimize the diagnostic workup of the patients and to develop new treatments. The main goal of the present paper is to provide an updated scenario of the current knowledge regarding the role of inflammation in "dry" and "wet" AMD and to discuss new possible therapeutic strategies.},
}
@article {pmid36649236,
year = {2023},
author = {Cohen-Gulkar, M and David, A and Messika-Gold, N and Eshel, M and Ovadia, S and Zuk-Bar, N and Idelson, M and Cohen-Tayar, Y and Reubinoff, B and Ziv, T and Shamay, M and Elkon, R and Ashery-Padan, R},
title = {The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration.},
journal = {PLoS biology},
volume = {21},
number = {1},
pages = {e3001924},
pmid = {36649236},
issn = {1545-7885},
mesh = {Humans ; Mice ; Animals ; LIM-Homeodomain Proteins/genetics/metabolism ; Genome-Wide Association Study ; Proteomics ; *Macular Degeneration/genetics/metabolism ; Cell Differentiation ; Epithelium/metabolism ; Transcription Factors/genetics/metabolism ; *TRPM Cation Channels/genetics ; Otx Transcription Factors/genetics/metabolism ; DNA-Binding Proteins/metabolism ; LIM Domain Proteins/genetics/metabolism ; },
abstract = {Tissue-specific transcription factors (TFs) control the transcriptome through an association with noncoding regulatory regions (cistromes). Identifying the combination of TFs that dictate specific cell fate, their specific cistromes and examining their involvement in complex human traits remain a major challenge. Here, we focus on the retinal pigmented epithelium (RPE), an essential lineage for retinal development and function and the primary tissue affected in age-related macular degeneration (AMD), a leading cause of blindness. By combining mechanistic findings in stem-cell-derived human RPE, in vivo functional studies in mice and global transcriptomic and proteomic analyses, we revealed that the key developmental TFs LHX2 and OTX2 function together in transcriptional module containing LDB1 and SWI/SNF (BAF) to regulate the RPE transcriptome. Importantly, the intersection between the identified LHX2-OTX2 cistrome with published expression quantitative trait loci, ATAC-seq data from human RPE, and AMD genome-wide association study (GWAS) data, followed by functional validation using a reporter assay, revealed a causal genetic variant that affects AMD risk by altering TRPM1 expression in the RPE through modulation of LHX2 transcriptional activity on its promoter. Taken together, the reported cistrome of LHX2 and OTX2, the identified downstream genes and interacting co-factors reveal the RPE transcription module and uncover a causal regulatory risk single-nucleotide polymorphism (SNP) in the multifactorial common blinding disease AMD.},
}
@article {pmid36648560,
year = {2023},
author = {Sakai, D and Hiraoka, M and Matsuzaki, M and Yokota, S and Hirami, Y and Onishi, A and Nakamura, M and Takahashi, M and Kurimoto, Y and Maeda, A},
title = {Genotype and phenotype characteristics of RHO-associated retinitis pigmentosa in the Japanese population.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {2},
pages = {138-148},
pmid = {36648560},
issn = {1613-2246},
mesh = {Humans ; Rhodopsin/genetics ; Cross-Sectional Studies ; East Asian People ; Tomography, Optical Coherence/methods ; *Retinitis Pigmentosa/diagnosis/genetics ; Phenotype ; Genotype ; *Macular Degeneration ; },
abstract = {PURPOSE: To identify the genotypic and phenotypic characteristics of rhodopsin (RHO)-associated retinitis pigmentosa (RP) in the Japanese population.<br><br>STUDY DESIGN: Cross-sectional, single-center study METHODS: The medical records of 1336 patients with RP who underwent genetic testing at our clinic between November 2008 and September 2021 were reviewed, and patients with RHO variants were included. The patients were divided into class A and class B to assess genotype-phenotype correlations based on previous reports. The clinical findings, including best-corrected visual acuity (BCVA), OCT parameters (ellipsoid zone [EZ] width and central retinal thickness [CRT]), and presence of macular degeneration, of the 2 groups were compared.<br><br>RESULTS: The study included 28 patients diagnosed with RHO-associated RP (class A, 19; class B, 9). The BCVA was significantly worse in class A patients than in class B patients (P = 0.045). Superior EZ width was significantly shorter in class A than in class B patients (P = 0.016). Class A patients tended to have thinner CRT and shorter inferior EZ width than those of class B patients, although this difference was not significant. Macular degeneration was observed in 61.5% of class A and 12.5% of class B patients, demonstrating that macular degeneration can be a common complication in class A variants.<br><br>CONCLUSION: Patients with class A variants presented with a severer form of RP than that of patients with class B variants in the Japanese population. These results suggest that the phenotype of RHO-associated RP is linked to the location of the variants and that such a genotype-phenotype correlation is less affected by ethnicities with different genetic backgrounds.},
}
@article {pmid36645183,
year = {2023},
author = {Collin, J and Hasoon, MSR and Zerti, D and Hammadi, S and Dorgau, B and Clarke, L and Steel, D and Hussain, R and Coxhead, J and Lisgo, S and Queen, R and Lako, M},
title = {Single-cell RNA sequencing reveals transcriptional changes of human choroidal and retinal pigment epithelium cells during fetal development, in healthy adult and intermediate age-related macular degeneration.},
journal = {Human molecular genetics},
volume = {32},
number = {10},
pages = {1698-1710},
pmid = {36645183},
issn = {1460-2083},
support = {BB/T004460/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/R006237/1/MRC_/Medical Research Council/United Kingdom ; MR/S035826/1/MRC_/Medical Research Council/United Kingdom ; MR/X001687/1/MRC_/Medical Research Council/United Kingdom ; NC/C016106/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; },
mesh = {Humans ; Adult ; *Retinal Pigment Epithelium/metabolism ; Endothelial Cells/metabolism ; Choroid/metabolism ; *Macular Degeneration/genetics/metabolism ; Fetal Development ; Sequence Analysis, RNA ; },
abstract = {Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the developed world. Vision loss in the advanced stages of the disease is caused by atrophy of retinal photoreceptors, overlying retinal pigment epithelium (RPE) and choroidal endothelial cells. The molecular events that underline the development of these cell types from in utero to adult as well as the progression to intermediate and advanced stages AMD are not yet fully understood. We performed single-cell RNA-sequencing (RNA-Seq) of human fetal and adult RPE-choroidal tissues, profiling in detail all the cell types and elucidating cell type-specific proliferation, differentiation and immunomodulation events that occur up to midgestation. Our data demonstrate that progression from the fetal to adult state is characterized by an increase in expression of genes involved in the oxidative stress response and detoxification from heavy metals, suggesting a better defence against oxidative stress in the adult RPE-choroid tissue. Single-cell comparative transcriptional analysis between a patient with intermediate AMD and an unaffected subject revealed a reduction in the number of RPE cells and melanocytes in the macular region of the AMD patient. Together these findings may suggest a macular loss of RPE cells and melanocytes in the AMD patients, but given the complex processing of tissues required for single-cell RNA-Seq that is prone to technical artefacts, these findings need to be validated by additional techniques in a larger number of AMD patients and controls.},
}
@article {pmid36644458,
year = {2022},
author = {Falavarjani, KG and Anvari, P and Alemzadeh, SA and Moghaddam, MMJ and Habibi, A and Ashrafkhorasani, M},
title = {Segmentation Error Correction of the Optical Coherence Tomography Angiography Images in Peer-Reviewed Studies.},
journal = {Journal of current ophthalmology},
volume = {34},
number = {3},
pages = {273-276},
pmid = {36644458},
issn = {2452-2325},
abstract = {PURPOSE: To assess the percentage of published articles reporting optical coherence tomography angiography (OCTA) metrics regarding the report of segmentation error correction.<br><br>METHODS: A comprehensive search was conducted using the PubMed database for articles on OCTA imaging published between January 1, 2015, and January 1, 2021. All original articles reporting at least one of the OCTA metrics were extracted. The article text was reviewed for the segmentation correction strategy. In addition, the number of articles that mentioned the lack of segmentation error correction as a limitation of the study was recorded.<br><br>RESULTS: From the initial 5288 articles, 1559 articles were included for detailed review. One hundred ninety-six articles (12.57%) used manual correction for segmentation errors. Of the remaining articles, 589 articles (37.8%) excluded images with significant segmentation errors, and 99 articles (6.3%) mentioned segmentation errors as a limitation of their study. The rest of the articles (675, 43.3%) did not address the segmentation error. Multiple logistic regression analysis revealed that ignorance of segmentation error was significantly associated with lower journal ranks, earlier years of publication and disease category of age-related macular degeneration, and glaucoma (all P < 0.001).<br><br>CONCLUSIONS: A significant proportion of peer-reviewed articles in PubMed, disregarded the segmentation error correction. The conclusions of such studies should be interpreted with caution. Editors, reviewers, and authors of OCTA articles should pay special attention to the correction of segmentation errors.},
}
@article {pmid36644394,
year = {2023},
author = {Cho, HM and Lee, SJ and Choung, SY},
title = {Protective effects of Panax ginseng berry extract on blue light-induced retinal damage in ARPE-19 cells and mouse retina.},
journal = {Journal of ginseng research},
volume = {47},
number = {1},
pages = {65-73},
pmid = {36644394},
issn = {1226-8453},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a significant visual disease that induces impaired vision and irreversible blindness in the elderly. However, the effects of ginseng berry extract (GBE) on the retina have not been studied. Therefore, this study aimed to investigate the protective effects of GBE on blue light (BL)-induced retinal damage and elucidate its underlying mechanisms in human retinal pigment epithelial cells (ARPE-19 cells) and Balb/c retina.<br><br>METHODS: To investigate the effects and underlying mechanisms of GBE on retinal damage in&#xa0;vitro, we performed cell viability assay, pre-and post-treatment of sample, reactive oxygen species (ROS) assay, quantitative real-time PCR (qRT-PCR), and western immunoblotting using A2E-laden ARPE-19&#xa0;cells with BL exposure. In addition, Balb/c mice were irradiated with BL to induce retinal degeneration and orally administrated with GBE (50, 100, 200&#xa0;mg/kg). Using the harvested retina, we performed histological analysis (thickness of retinal layers), qRT-PCR, and western immunoblotting to elucidate the effects and mechanisms of GBE against retinal damage in&#xa0;vivo.<br><br>RESULTS: GBE significantly inhibited BL-induced cell damage in ARPE-19&#xa0;cells by activating the SIRT1/PGC-1&#x3b1; pathway, regulating NF-kB translocation, caspase 3 activation, PARP cleavage, expressions of apoptosis-related factors (BAX/BCL-2, LC3-&#x2161;, and p62), and ROS production. Furthermore, GBE prevented BL-induced retinal degeneration by restoring the thickness of retinal layers and suppressed inflammation and apoptosis via regulation of NF-kB and SIRT1/PGC-1&#x3b1; pathway, cleavage of caspase 3 and PARP, and expressions of apoptosis-related factors in&#xa0;vivo.<br><br>CONCLUSIONS: GBE could be a potential agent to prevent dry AMD and progression to wet AMD.},
}
@article {pmid36643920,
year = {2022},
author = {Hallam, TM and Cox, TE and Smith-Jackson, K and Brocklebank, V and Baral, AJ and Tzoumas, N and Steel, DH and Wong, EKS and Shuttleworth, VG and Lotery, AJ and Harris, CL and Marchbank, KJ and Kavanagh, D},
title = {A novel method for real-time analysis of the complement C3b:FH:FI complex reveals dominant negative CFI variants in age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {1028760},
pmid = {36643920},
issn = {1664-3224},
support = {/DH_/Department of Health/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/R000913/1/MRC_/Medical Research Council/United Kingdom ; MR/R001359/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Complement C3b/genetics ; *Macular Degeneration/genetics ; *Complement Factor H/genetics ; *Complement Factor I/genetics ; },
abstract = {Age-related macular degeneration (AMD) is linked to 2 main disparate genetic pathways: a chromosome 10 risk locus and the alternative pathway (AP) of complement. Rare genetic variants in complement factor H (CFH; FH) and factor I (CFI; FI) are associated with AMD. FH acts as a soluble cofactor to facilitate FI's cleavage and inactivation of the central molecule of the AP, C3b. For personalised treatment, sensitive assays are required to define the functional significance of individual AP genetic variants. Generation of recombinant FI for functional analysis has thus far been constrained by incomplete processing resulting in a preparation of active and inactive protein. Using an internal ribosomal entry site (IRES)-Furin-CFI expression vector, fully processed FI was generated with activity equivalent to serum purified FI. By generating FI with an inactivated serine protease domain (S525A FI), a real-time surface plasmon resonance assay of C3b:FH:FI complex formation for characterising variants in CFH and CFI was developed and correlated well with standard assays. Using these methods, we further demonstrate that patient-associated rare genetic variants lacking enzymatic activity (e.g. CFI I340T) may competitively inhibit the wild-type FI protein. The dominant negative effect identified in inactive factor I variants could impact on the pharmacological replacement of FI currently being investigated for the treatment of dry AMD.},
}
@article {pmid36643635,
year = {2023},
author = {Lee, D and Nakai, A and Miwa, Y and Negishi, K and Tomita, Y and Kurihara, T},
title = {Pemafibrate prevents choroidal neovascularization in a mouse model of neovascular age-related macular degeneration.},
journal = {PeerJ},
volume = {11},
number = {},
pages = {e14611},
pmid = {36643635},
issn = {2167-8359},
mesh = {Mice ; Male ; Animals ; PPAR alpha/therapeutic use ; Vascular Endothelial Growth Factor A/metabolism ; Mice, Inbred C57BL ; *Choroidal Neovascularization/drug therapy ; Disease Models, Animal ; *Macular Degeneration/drug therapy ; },
abstract = {BACKGROUND: Pathological choroidal neovascularization (CNV) is one of the major causes of visual impairment in neovascular age-related macular degeneration (AMD). CNV has been suppressed by using anti-vascular endothelial growth factor (VEGF) antibodies. However, some clinical cases have demonstrated the failure of anti-VEGF therapies. Furthermore, anti-VEGF agents might induce the development of ocular atrophy. Recently, peroxisome proliferator-activated receptor alpha (PPARα) activation using pemafibrate treatment was suggested as one of the promising therapeutic targets in the prevention of ocular ischemia. However, the preventive role of pemafibrate remains unclear in CNV. We aimed to examine the preventive role of pemafibrate on laser-induced pathological CNV.<br><br>METHODS: Adult male C57BL/6 mice were orally supplied pemafibrate (0.5 mg/kg) for four days, followed by laser irradiation. Then, pemafibrate was consecutively given to mice with the same condition. CNV was visualized with isolectin-IB4. The eye (retina and/or retinal pigment epithelium [RPE]-choroid), liver, and serum were used for biomolecular analyses.<br><br>RESULTS: We found that pemafibrate administration suppressed CNV volumes. Pemafibrate administration activated PPAR&#x3b1; downstream genes in the liver and eye (especially, RPE-choroid). Furthermore, pemafibrate administration elevated serum fibroblast growth factor 21 levels and reduced serum levels of triglycerides.<br><br>CONCLUSIONS: Our data suggest a promising pemafibrate therapy for suppressing CNV in AMD.},
}
@article {pmid36639223,
year = {2024},
author = {Zhang, Y and Gan, Y and Zeng, Y and Zhuang, X and Zhang, X and Ji, Y and Su, Y and Wen, F},
title = {Incidence and multimodal imaging characteristics of macular neovascularisation subtypes in Chinese neovascular age-related macular degeneration patients.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {3},
pages = {391-397},
doi = {10.1136/bjo-2022-322392},
pmid = {36639223},
issn = {1468-2079},
mesh = {Humans ; Male ; Retrospective Studies ; Choroid/pathology ; Incidence ; Fluorescein Angiography ; *Macular Degeneration/diagnosis/epidemiology/pathology ; *Retinal Neovascularization/pathology ; Multimodal Imaging ; China/epidemiology ; *Wet Macular Degeneration/diagnosis/epidemiology/pathology ; Tomography, Optical Coherence ; *Choroidal Neovascularization/diagnosis/epidemiology/pathology ; },
abstract = {AIMS: To investigate the incidence of macular neovascularisation (MNV) subtypes of neovascular age-related macular degeneration (nAMD) and summarise these subtypes' clinical features in the Chinese population using multimodal imaging.<br><br>METHODS: We retrospectively analysed 506 consecutive treatment-na&#xef;ve nAMD patients (582 eyes). Incidence of MNV subtypes and clinical features were recorded based on their multimodal images. The classification of MNV subtypes in nAMD patients were referred to Consensus on Neovascular Age-related Macular Degeneration Nonmenclature (CONAN) study group classifications.<br><br>RESULTS: 460 eyes of 389 nAMD patients were included in our study. 68.5% (315/460) of nAMD eyes were from male. According to CONAN, we identified type 1 macular neovascularisation (MNV) in 61.1% of eyes (281/460), type 2 MNV in 16.3% of eyes (75/460), type 3 MNV in 2.0% of eyes (9/460), mixed type 1 and type 2 MNV in 20.6% of eyes (95/460). 58% of eyes (267/460) were diagnosed as polypoidal choroidal vasculopathy lesions (PCV). 45.2% of eyes (208/460) with PCV lesions were type 1 MNV and 12.8% of eyes (59/460) with PCV lesions were co-occurred with type 2 MNV.<br><br>CONCLUSION: Based on the consensus anatomical classification system developed by the CONAN Study Group, we updated the incidence of MNV subtypes and found that PCV was the most common subtype and type 3 MNV was the least common subtype among Chinese nAMD patients. In addition, the co-occurrence of PCV and type 2 MNV was typically observed, and its frequency was reported in our study.},
}
@article {pmid36638858,
year = {2023},
author = {Xu, M and Shen, YM and Han, XY and Liu, C and Jiang, Q and Cao, X and Yan, B},
title = {"One stone and two birds" strategy to treat neovascular age-related macular degeneration by a novel retinoid drug, EYE-101.},
journal = {Experimental eye research},
volume = {227},
number = {},
pages = {109385},
doi = {10.1016/j.exer.2023.109385},
pmid = {36638858},
issn = {1096-0007},
mesh = {Humans ; Aged ; Pharmaceutical Preparations ; Endothelial Cells ; Retinoids/therapeutic use ; Vascular Endothelial Growth Factor A/pharmacology ; *Choroidal Neovascularization/pathology ; Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy ; },
abstract = {Choroidal neovascularization (CNV) is a typical pathological feature of neovascular age-related macular degeneration and has become a major cause of vision loss in the elderly. Current therapies require repeated intraocular injections of anti-VEGF drugs by inhibiting endothelial angiogenic effects, which is painful and may cause adverse effects on normal vascular and neuronal functions. Herein, we designed a novel retinoid drug, EYE-101, determined its therapeutic effects on CNV, and clarified the anti-angiogenic mechanism. The results show that administration of EYE-101 did not cause obvious cytotoxicity and ocular tissue toxicity at the concentrations less than 5 μM. Topical administration of EYE-101 could reduce choroidal sprouting, suppress laser-induced CNV formation, and decrease pericyte coverages on ocular vessels. Administration of EYE-101 also suppressed endothelial cell proliferation, migration, and tube formation and reduced pericyte proliferation, migration, recruitment towards endothelial cells. EYE-101 exerted its anti-angiogenic effects by targeting endothelial cells and pericytes via antagonizing Wnt/β-catenin signaling and PDGF signaling. Thus, EYE-101 administration may offer an"one stone and two birds" strategy for the prevention and treatment of ocular neovascular disorders.},
}
@article {pmid36638800,
year = {2023},
author = {Tay, HG and Andre, H and Chrysostomou, V and Adusumalli, S and Guo, J and Ren, X and Tan, WS and Tor, JE and Moreno-Moral, A and Plastino, F and Bartuma, H and Cai, Z and Tun, SBB and Barathi, VA and Siew Wei, GT and Grenci, G and Chong, LY and Holmgren, A and Kvanta, A and Crowston, JG and Petretto, E and Tryggvason, K},
title = {Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {31},
number = {3},
pages = {825-846},
pmid = {36638800},
issn = {1525-0024},
mesh = {Humans ; Mice ; Animals ; Rabbits ; Laminin/genetics ; Retina ; Photoreceptor Cells ; *Retinal Degeneration/genetics/therapy ; *Pluripotent Stem Cells ; Cell Differentiation ; },
abstract = {Blindness caused by advanced stages of inherited retinal diseases and age-related macular degeneration are characterized by photoreceptor loss. Cell therapy involving replacement with functional photoreceptor-like cells generated from human pluripotent stem cells holds great promise. Here, we generated a human recombinant retina-specific laminin isoform, LN523, and demonstrated the role in promoting the differentiation of human embryonic stem cells into photoreceptor progenitors. This chemically defined and xenogen-free method enables reproducible production of photoreceptor progenitors within 32 days. We observed that the transplantation into rd10 mice were able to protect the host photoreceptor outer nuclear layer (ONL) up to 2 weeks post transplantation as measured by full-field electroretinogram. At 4 weeks post transplantation, the engrafted cells were found to survive, mature, and associate with the host's rod bipolar cells. Visual behavioral assessment using the water maze swimming test demonstrated visual improvement in the cell-transplanted rodents. At 20 weeks post transplantation, the maturing engrafted cells were able to replace the loss of host ONL by extensive association with host bipolar cells and synapses. Post-transplanted rabbit model also provided congruent evidence for synaptic connectivity with the degenerated host retina. The results may pave the way for the development of stem cell-based therapeutics for retina degeneration.},
}
@article {pmid36638665,
year = {2023},
author = {Wang, Y and Han, S and Chen, J and Sun, J and Sun, X},
title = {PFKFB3 knockdown attenuates Amyloid β-Induced microglial activation and retinal pigment epithelium disorders in mice.},
journal = {International immunopharmacology},
volume = {115},
number = {},
pages = {109691},
doi = {10.1016/j.intimp.2023.109691},
pmid = {36638665},
issn = {1878-1705},
mesh = {Mice ; Animals ; *Retinal Pigment Epithelium ; Microglia ; Amyloid beta-Peptides/metabolism ; Neuroinflammatory Diseases ; Retina/pathology ; *Macular Degeneration/genetics ; },
abstract = {Age-related macular degeneration (AMD) is characterized by progressive accumulation of drusen deposits and retinal pigment epithelium (RPE) disorders. As the main component of drusen, amyloid β (Aβ) plays a critical role in activating microglia and causing neuroinflammation in AMD pathogenesis. However, the role of activated microglia-mediated neuroinflammation in RPE senescence remains unclear. Recent evidence indicates that inflammatory microglia are glycolytic and driven by an increase in 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), an enzyme described as the master regulator of glycolysis. In this study, we mimicked the retinal inflammatory microenvironment of AMD by intravitreal injection of oligomeric Aβ1-40 in mice, which resulted in activation of microglia and upregulation of PFKFB3. RNA sequencing was performed to evaluate PFKFB3-mediated microglial activation. The effect of microglial activation on RPE disorders was assessed using gene knockout experiments, immunofluorescence, CCK-8 assay, and β-galactosidase staining. Intravitreal Aβ1-40 injection induced proinflammatory activation of microglia by upregulating PFKFB3 and resulted in RPE disorders, which was verified in heterozygous Pfkfb3-deficient mice (Pfkfb3[+/-]) mice, Aβ1-40-activated microglial cell line BV2, and co-culture of RPE cell line ARPE19. RNA sequencing revealed that PFKFB3 mainly affected innate immune processes during Aβ1-40-induced retinal inflammation. PFKFB3 knockdown inhibited RPE disorders and rescued the retinal structure and function. Overall, the modulation of PFKFB3-mediated microglial glycolysis and activation is a promising strategy for AMD treatment.},
}
@article {pmid36636621,
year = {2023},
author = {Sen, P and Manayath, G and Shroff, D and Salloju, V and Dhar, P},
title = {Polypoidal Choroidal Vasculopathy: An Update on Diagnosis and Treatment.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {17},
number = {},
pages = {53-70},
pmid = {36636621},
issn = {1177-5467},
abstract = {Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid that leads to hemorrhagic and exudative macular degeneration. It may cause significant vision loss and thus affect the quality-of-life and psychological well-being. Non-invasive, non-ICGA-based OCT criteria have shown reliable results to plan adjunct photodynamic therapy (PDT) treatment, with the complete and consistent coverage of polypoidal lesions (PL) and branching neovascular network (BNN). The safety and efficacy of anti-vascular endothelial growth factor (anti-VEGF) monotherapy and its combination with verteporfin PDT have been established. However, treatment is still challenging due to frequent follow-ups, non-availability of PDT, and need for multiple anti-VEGF injection visits that increase the treatment burden and lead to patients being lost to follow-up. Effective treatments that prolong intervals between injections while maintaining vision and anatomical gains remain a critical unmet need. Longer acting molecules, like brolucizumab, have shown non-inferiority in BCVA gains and superior anatomical outcomes compared to other anti-VEGF agents. Newer therapies in the pipeline to enhance the efficacy and longevity of treatment include Faricimab and a port delivery system (PDS). This review summarizes the most recent diagnostic and treatment approaches in PCV to offer better treatment avenues.},
}
@article {pmid36634357,
year = {2023},
author = {Wang, C and Fang, C and Zou, Y and Yang, J and Sawan, M},
title = {Artificial intelligence techniques for retinal prostheses: a comprehensive review and future direction.},
journal = {Journal of neural engineering},
volume = {20},
number = {1},
pages = {},
doi = {10.1088/1741-2552/acb295},
pmid = {36634357},
issn = {1741-2552},
mesh = {Humans ; *Visual Prosthesis ; Artificial Intelligence ; Retina ; *Retinitis Pigmentosa ; *Macular Degeneration ; },
abstract = {Objective. Retinal prostheses are promising devices to restore vision for patients with severe age-related macular degeneration or retinitis pigmentosa disease. The visual processing mechanism embodied in retinal prostheses play an important role in the restoration effect. Its performance depends on our understanding of the retina's working mechanism and the evolvement of computer vision models. Recently, remarkable progress has been made in the field of processing algorithm for retinal prostheses where the new discovery of the retina's working principle and state-of-the-arts computer vision models are combined together.Approach. We investigated the related research on artificial intelligence techniques for retinal prostheses. The processing algorithm in these studies could be attributed to three types: computer vision-related methods, biophysical models, and deep learning models.Main results. In this review, we first illustrate the structure and function of the normal and degenerated retina, then demonstrate the vision rehabilitation mechanism of three representative retinal prostheses. It is necessary to summarize the computational frameworks abstracted from the normal retina. In addition, the development and feature of three types of different processing algorithms are summarized. Finally, we analyze the bottleneck in existing algorithms and propose our prospect about the future directions to improve the restoration effect.Significance. This review systematically summarizes existing processing models for predicting the response of the retina to external stimuli. What's more, the suggestions for future direction may inspire researchers in this field to design better algorithms for retinal prostheses.},
}
@article {pmid36633874,
year = {2023},
author = {Chandra, RS and Ying, GS},
title = {Evaluation of Multiple Machine Learning Models for Predicting Number of Anti-VEGF Injections in the Comparison of AMD Treatment Trials (CATT).},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {1},
pages = {18},
pmid = {36633874},
issn = {2164-2591},
support = {P30 EY001583/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Child, Preschool ; *Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; Ranibizumab/therapeutic use ; *Macular Degeneration/drug therapy ; Machine Learning ; },
abstract = {PURPOSE: To apply machine learning models for predicting the number of pro re nata (PRN) injections of antivascular endothelial growth factor (anti-VEGF) for neovascular age-related macular degeneration (nAMD) in two years in the Comparison of AMD (age-related macular degeneration) Treatments Trials.<br><br>METHODS: The data from 493 eligible participants randomized to PRN treatment of ranibizumab or bevacizumab were used for training (n = 393) machine learning models including support-vector machine (SVM), random forest, and extreme gradient boosting (XGBoost) models. Model performances of prediction using clinical and image data from baseline, weeks 4, 8, and 12 were evaluated by the area under the receiver operating characteristic curve (AUC) for predicting few (&#x2264;8) or many (&#x2265;19) injections, by R2 and mean absolute error (MAE) for predicting the total number of injections in two years. The best model was selected for final validation on a test dataset (n = 100).<br><br>RESULTS: Using training data up to week 12, the models achieved AUCs of 0.79-0.82 and 0.79-0.81 for predicting few and many injections, respectively, with R2 of 0.34-0.36 (MAE = 4.45-4.58 injections) for predicting total injections in two years from cross-validation. In final validation on the test dataset, the SVM model had AUCs of 0.77 and 0.82 for predicting few and many injections, respectively, with R2 of 0.44 (MAE = 3.92 injections). Important features included fluid in optical coherence tomography, lesion characteristics, and treatment trajectory in the first three months.<br><br>CONCLUSIONS: Machine learning models using loading dose phase data have the potential to predict two-year anti-VEGF demand for nAMD and quantify feature importance for these predictions.<br><br>TRANSLATIONAL RELEVANCE: Prediction of anti-VEGF injections using machine learning models from readily available data, after further validation on independent datasets, has the potential to help optimize treatment protocols and outcomes for nAMD patients in an individualized manner.},
}
@article {pmid36633873,
year = {2023},
author = {Fonteh, CN and Palestine, AG and Wagner, BD and Patnaik, JL and Mathias, MT and Manoharan, N and Mandava, N and Baldermann, R and De Carlo, T and Lynch, AM and , },
title = {RANTES (CCL5) in Patients With Geographic Atrophy Age-Related Macular Degeneration.},
journal = {Translational vision science &amp; technology},
volume = {12},
number = {1},
pages = {19},
pmid = {36633873},
issn = {2164-2591},
support = {UL1 TR002535/TR/NCATS NIH HHS/United States ; R01 EY032456/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *Geographic Atrophy ; *Macular Degeneration ; Biomarkers ; Fluorescein Angiography ; Visual Acuity ; Chemokine CCL5 ; },
abstract = {PURPOSE: A previous study from our research group showed significantly lower levels of RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in patients with intermediate age-related macular degeneration (AMD) compared to control patients with no AMD. The primary aim of this study was to assess levels of RANTES in a cohort of patients with a more advanced form of the disease, geographic atrophy (GA), in comparison with controls.<br><br>METHODS: The study was conducted on a cohort of patients with GA recruited into a Colorado AMD registry. Cases and controls were defined with multimodal imaging. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction.<br><br>RESULTS: The plasma levels of RANTES were significantly higher in the control group in comparison to the GA AMD group (median [interquartile range]): 10,204 [5799-19,554] pg/mL vs. 5435 [3420-9177] pg/mL, respectively, P < 0.01). When moderated by sex, there was no statistical difference between the male and female GA AMD or the male and female controls.<br><br>CONCLUSIONS: We found lower level of RANTES in patients with GA AMD compared with controls. This finding is consistent with the findings from our previous intermediate AMD study. However, in contrast to the results of our previous research, when moderated by sex there was no statistical difference between male and female GA patients.<br><br>TRANSLATIONAL RELEVANCE: The biomarker RANTES is significantly lower in GA AMD patients compared to controls.},
}
@article {pmid36633780,
year = {2023},
author = {Garweg, JG and Blum, CA and Copt, RP and Eandi, CM and Hatz, K and Prünte, CF and Seelig, E and Somfai, GM},
title = {Brolucizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: Ophthalmology and Diabetology Treatment Aspects.},
journal = {Ophthalmology and therapy},
volume = {12},
number = {2},
pages = {639-655},
pmid = {36633780},
issn = {2193-8245},
abstract = {Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events.},
}
@article {pmid36633669,
year = {2023},
author = {Pur, DR and Lee-Wing, N and Bona, MD},
title = {The use of augmented reality and virtual reality for visual field expansion and visual acuity improvement in low vision rehabilitation: a systematic review.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {6},
pages = {1743-1755},
pmid = {36633669},
issn = {1435-702X},
mesh = {Humans ; Middle Aged ; *Augmented Reality ; Visual Fields ; *Vision, Low ; *Virtual Reality ; Visual Acuity ; },
abstract = {INTRODUCTION: Developments in image processing techniques and display technology have led to the emergence of augmented reality (AR) and virtual reality (VR)-based low vision devices (LVDs). However, their promise and limitations in low vision rehabilitation are poorly understood. The objective of this systematic review is to appraise the application of AR/VR LVDs aimed at visual field expansion and visual acuity improvement in low vision rehabilitation.<br><br>METHODS: A systematic search of the literature was performed using MEDLINE, Embase, PsychInfo, HealthStar, and National Library of Medicine (PubMed) from inception to March 6, 2022. Articles were eligible if they included an AR or VR LVD tested on a sample of individuals with low vision and provided visual outcomes such as visual acuity, visual fields, and object recognition.<br><br>RESULTS: Of the 652 articles identified, 16 studies comprising 382 individuals with a mean age of 52.17 (SD&#x2009;=&#x2009;18.30) years, and with heterogeneous low vision etiologies (i.e., glaucoma, age-related macular degeneration, retinitis pigmentosa) were included in this systematic review. Most articles used AR (53%), VR (40%), and one article used both AR and VR. The main visual outcomes evaluated were visual fields (67%), visual acuity (65%), and contrast sensitivity (27%). Various visual enhancement techniques were employed including variable magnification using digital zoom (67%), contrast enhancements (53%), and minification (27%). AR LVDs were reported to expand the visual field from threefold to ninefold. On average, individuals using AR/VR LVDs experienced an improved in visual acuity from 0.9 to 0.2 logMAR. Ten articles were classified as high or moderate risk of bias.<br><br>CONCLUSION: AR/VR LVDs were found to afford visual field expansion and visual acuity improvement in low vision populations. Even though the results of this review are promising, the lack of controlled studies with well-defined populations, use of small, convenience samples, and incomplete reporting of inclusion and exclusion criteria among included studies makes it challenging to judge the true impact of these devices. Future studies should address these limitations and compare various AR/LVDs to determine what is the ideal LVD type and vision enhancement combination based on the user's level of visual ability and lifestyle.},
}
@article {pmid36633668,
year = {2023},
author = {Riemer, T and Berndt, D and Böker, A and Lehmann, J and Schrifl, U and Rau, S and Rübsam, A and Joussen, AM and Zeitz, O},
title = {Treatment of neovascular age-related macular degeneration: insights into drug-switch real-world from the Berlin Macular Registry.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {6},
pages = {1681-1690},
pmid = {36633668},
issn = {1435-702X},
mesh = {Humans ; *Ranibizumab ; Bevacizumab ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Berlin ; Receptors, Vascular Endothelial Growth Factor ; Registries ; *Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/therapeutic use ; Intravitreal Injections ; Treatment Outcome ; },
abstract = {PURPOSE: Bevacizumab, ranibizumab, and aflibercept are commonly used to treat neovascular age-related macular degeneration (nAMD). The results of various interventional, mostly randomized head-to-head studies, indicate statistical non-inferiority of these three drugs. The results of these studies are often interpreted as the three drugs being freely interchangeable, resulting in some health systems to pressure ophthalmologists to preferentially use the less expensive bevacizumab. This study analyzes switching from aflibercept or ranibizumab to bevacizumab and back under real-world conditions in order to investigate the assumption of interchangeability of the drugs.<br><br>METHODS: Treatment data of IVT patients with diagnosed nAMD were extracted from the clinical Berlin Macular Registry database. Patients who underwent a drug switch from aflibercept or ranibizumab to bevacizumab were subject of this study. Statistical comparisons were pre-planned for best corrected visual acuity, central retinal thickness, macular volume, and length of injection interval. Additional endpoints were analyzed descriptively.<br><br>RESULTS: Mean visual acuity decreased from 0.57&#x2009;&#xb1;&#x2009;0.05 under aflibercept/ranibizumab to 0.68&#x2009;&#xb1;&#x2009;0.06 logMAR after the switch (P&#x2009;=&#x2009;0.001; N&#x2009;=&#x2009;63). CRT increased from 308&#x2009;&#xb1;&#x2009;11&#xa0;&#xb5;m to 336&#x2009;&#xb1;&#x2009;16&#xa0;&#xb5;m (P&#x2009;=&#x2009;0.011; N&#x2009;=&#x2009;63). About half of the subjects were switched back: visual acuity increased from 0.69&#x2009;&#xb1;&#x2009;0.08 logMAR to 0.58&#x2009;&#xb1;&#x2009;0.09 logMAR (N&#x2009;=&#x2009;26). CRT decreased from 396&#x2009;&#xb1;&#x2009;28 to 337&#x2009;&#xb1;&#x2009;20&#xa0;&#xb5;m (N&#x2009;=&#x2009;28).<br><br>CONCLUSION: The data provides real-world evidence that there is loss of visual acuity and an increase in retinal edema after switching to bevacizumab. Thus, the assumption of free interchangeability cannot be confirmed in this cohort.},
}
@article {pmid36632450,
year = {2023},
author = {Zhang, Q and Hu, XM and Zhao, WJ and Ban, XX and Li, Y and Huang, YX and Wan, H and He, Y and Liao, LS and Shang, L and Jiang, B and Qing, GP and Xiong, K},
title = {Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases.},
journal = {International journal of biological sciences},
volume = {19},
number = {2},
pages = {658-674},
pmid = {36632450},
issn = {1449-2288},
mesh = {Humans ; Protein Kinases/metabolism ; *Necroptosis/drug effects ; *Retinal Degeneration/drug therapy/pathology ; },
abstract = {The discovery of the necroptosis, a form of regulated necrosis that is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like pseudokinase (MLKL), represents a major breakthrough that has dramatically altered the conception of necrosis - traditionally thought of as uncontrolled cell death - in various human diseases. Retinal cell death is a leading cause of blindness and has been identified in most retinal diseases, e.g., age-related macular degeneration, glaucoma, retinal detachment, retinitis pigmentosa, etc. Increasing evidence demonstrates that retinal degenerative diseases also share a common mechanism in necroptosis. Exacerbated necroptotic cell death hinders the treatment for retinal degenerative diseases. In this review, we highlight recent advances in identifying retinal necroptosis, summarize the underlying mechanisms of necroptosis in retinal degenerative diseases, and discuss potential anti-necroptosis strategies, such as selective inhibitors and chemical agents, for treating retinal degenerative diseases.},
}
@article {pmid36632338,
year = {2023},
author = {Hirano, T and Toriyama, Y and Takahashi, Y and Hoshiyama, K and Murata, T},
title = {Retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab injections for diabetic macular edema.},
journal = {American journal of ophthalmology case reports},
volume = {29},
number = {},
pages = {101788},
pmid = {36632338},
issn = {2451-9936},
abstract = {PURPOSE: To describe a case of unilateral retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab (IVBr) treatments for diabetic macular edema (DME).<br><br>OBSERVATIONS: A 68-year-old Japanese woman who had a 3-year history of insulin-dependent diabetes mellitus presented with decreased vision in the right eye (oculus dexter, OD). After two consecutive IVBr (3 mg) treatments for DME, spaced 6 weeks apart, her best corrected visual acuity improved from 20/32 to 20/28 OD, as central macular thickness (CMT) decreased from 368 &#x3bc;m to 253 &#x3bc;m on optical coherence tomography (OCT). Immediately after the 3rd IVBr, the right intraocular pressure (IOP) increased. One week later, iritis (aqueous flares: 65.0 photon count [PC]/ms) was observed, followed by localized vasculitis 2 weeks later. One month after the 3rd IVBr, extensive vasculitis and vasculitis occluding retinal arterioles were identified. Based on the history of IVBr use and clinical findings, intraocular inflammation (IOI) and subsequent retinal arterial occlusive vasculitis due to IVBr was diagnosed. Topical steroid administration (i.e., eye drops and subtenon injection) resulted in improvement of IOI after 3 months. She subsequently underwent two intravitreal aflibercept injections for DME and panretinal photocoagulation (PRP) to prevent the development of proliferative changes due to diabetic retinopathy. One year after the diagnosis of retinal arterial occlusive vasculitis, the patient had slight loss of vision (20/50) compared to baseline, due to the progression of cataracts, and OCT angiography (OCTA) showed extensive non-perfusion area on the temporal side. However, other examination findings (IOP: 16&#xa0;mmHg, aqueous flares: 30.5 PC/ms, CMT: 283 &#x3bc;m) were stable.<br><br>CONCLUSIONS AND IMPORTANCE: Diagnosis and treatment at a relatively early stage after the onset of IOI prevented severe visual impairment in this case. Topical betamethasone eye drops reduced anterior chamber inflammation associated with IVBr; however, vascular sheathing worsened when topical drops alone was used. Occlusive retinal vasculitis, diagnosed with fluorescein angiography (FA) and OCTA, appeared to stabilize when subtenon triamcinolone injection was added to topical steroid administration. Because the central macula was not involved, severe vision loss was prevented. It is unknown if topical steroid administration would be adequate to prevent worsening of occlusive vasculitis in other cases. Although not used in this case, oral prednisone is one treatment option that may prevent severe vision loss. However, it requires monitoring of side effects, such as elevated blood glucose levels. PRP is also an option in cases where progression of proliferative changes is a concern, as was done in this case. With these considerations in mind, it is important to diagnose brolucizumab-associated IOI and subsequent retinal arterial occlusive vasculitis in DME patients early and initiate treatment to prevent severe visual impairment. Diagnosing new IOI and subsequent retinal arterial occlusive vasculitis is more difficult in DME than in neovascular age-related macular degeneration because of the inflammatory component often associated vascular occlusions. Therefore, early IOI diagnosis and follow-up using various instruments such as laser flare cell meter, wide-field color imaging, OCT/OCTA, and FA, in addition to usual comprehensive ophthalmologic examinations, is crucial.},
}
@article {pmid36631073,
year = {2023},
author = {He, J and Liu, Y and Zhang, A and Liu, Q and Yang, X and Sun, N and Yao, B and Liang, F and Yan, X and Liu, Y and Mao, H and Chen, X and Tang, NJ and Yan, H},
title = {Joint effects of meteorological factors and PM2.5 on age-related macular degeneration: a national cross-sectional study in China.},
journal = {Environmental health and preventive medicine},
volume = {28},
number = {},
pages = {3},
pmid = {36631073},
issn = {1347-4715},
mesh = {Humans ; Adult ; Middle Aged ; Cross-Sectional Studies ; *Air Pollutants/analysis ; Particulate Matter/analysis ; China/epidemiology ; *Macular Degeneration/epidemiology/etiology ; Meteorological Concepts ; },
abstract = {BACKGROUND: Weather conditions are a possible contributing factor to age-related macular degeneration (AMD), a leading cause of irreversible loss of vision. The present study evaluated the joint effects of meteorological factors and fine particulate matter (PM2.5) on AMD.<br><br>METHODS: Data was extracted from a national cross-sectional survey conducted across 10 provinces in rural China. A total of 36,081 participants aged 40 and older were recruited. AMD was diagnosed clinically by slit-lamp ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (OCT). Meteorological data were calculated by European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and were matched to participants' home addresses by latitude and longitude. Participants' individual PM2.5 exposure concentrations were calculated by a satellite-based model at a 1-km resolution level. Multivariable-adjusted logistic regression models paired with interaction analysis were performed to investigate the joint effects of meteorological factors and PM2.5 on AMD.<br><br>RESULTS: The prevalence of AMD in the study population was 2.6% (95% CI 2.42-2.76%). The average annual PM2.5 level during the study period was 63.1 &#xb1; 15.3 &#xb5;g/m[3]. A significant positive association was detected between AMD and PM2.5 level, temperature (T), and relative humidity (RH), in both the independent and the combined effect models. For PM2.5, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) across increasing quartiles were 0.828 (0.674,1.018), 1.105 (0.799,1.528), and 2.602 (1.516,4.468). Positive associations were observed between AMD and temperature, with ORs (95% CI) of 1.625 (1.059,2.494), 1.619 (1.026,2.553), and 3.276 (1.841,5.830), across increasing quartiles. In the interaction analysis, the estimated relative excess risk due to interaction (RERI) and the attributable proportion (AP) for combined atmospheric pressure and PM2.5 was 0.864 (0.586,1.141) and 1.180 (0.768,1.592), respectively, indicating a synergistic effect between PM2.5 and atmospheric pressure.<br><br>CONCLUSIONS: This study is among the first to characterize the coordinated effects of meteorological factors and PM2.5 on AMD. The findings warrant further investigation to elucidate the relationship between ambient environment and AMD.},
}
@article {pmid36627843,
year = {2023},
author = {Dawn, A and Goswami, V and Sapra, S and Deep, S},
title = {Nano-Formulation of Antioxidants as Effective Inhibitors of γD-Crystallin Aggregation.},
journal = {Langmuir : the ACS journal of surfaces and colloids},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.langmuir.2c03263},
pmid = {36627843},
issn = {1520-5827},
abstract = {The aggregation of crystallin proteins is related to cataracts and age-related macular degeneration. Apart from surgical replacement of the cataract lens, no other alternative treatment is available till date for this ailment. In the current work, we carried out an in-depth investigation of the effect of polyphenol-loaded nano-formulations on the aggregation of γD-crystallin. At first, the protein was allowed to form amorphous aggregates under denaturing conditions. Several polyphenols were then tried to inhibit the aggregation of the protein. Among the polyphenols tested, resveratrol and quercetin were found to be the most effective. Since polyphenols are prone to degradation, they were encapsulated in chitosan nanoparticles in order to provide ambient conditions for them to function effectively. The loading efficiency and polyphenol release kinetics were subsequently tested. Finally, the efficacy of resveratrol/quercetin-loaded chitosan nano-particles as inhibitors of γD-crystallin aggregation was confirmed in a series of experiments demonstrating the potency of the system in the prospective therapeutic intervention of eye ailments concerning self-assembly of γD-crystallin proteins.},
}
@article {pmid36627583,
year = {2023},
author = {Gyenes, A and István, L and Benyó, F and Papp, A and Resch, M and Sándor, N and Józsi, M and Nagy, ZZ and Kovács, I and Kiss, S},
title = {Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration.},
journal = {BMC ophthalmology},
volume = {23},
number = {1},
pages = {14},
pmid = {36627583},
issn = {1471-2415},
mesh = {Humans ; Aged ; Aged, 80 and over ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; Ranibizumab/therapeutic use ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A ; Antibodies, Neutralizing/therapeutic use ; Visual Acuity ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Intravitreal Injections ; *Cataract/drug therapy ; Immunoglobulin G ; Recombinant Fusion Proteins/therapeutic use ; },
abstract = {PURPOSE: To detect immunoglobulins in aqueous humour of AMD patients after repeated administration of intravitreal aflibercept.<br><br>PATIENTS AND METHODS: Twenty-one patients (age: 77.85&#x2009;&#xb1;&#x2009;9.21&#x2009;years) previously treated with intravitreal aflibercept due to wet type age-related macular degeneration (AMD group) and 18 age-matched control subjects (age: 69.75&#x2009;&#xb1;&#x2009;12.67&#x2009;years) were included in this study. Patients in the AMD group received a mean of 5 intravitreal injections (min: 1 max: 17) prior to the cataract surgery. Samples of aqueous humour (50&#x2009;&#x3bc;l) were obtained by anterior chamber paracentesis as the first step of routine cataract surgery. The IgG content of the samples was analysed by an in-house developed ELISA system.<br><br>RESULTS: A significant increase in nonspecific IgG levels in the AMD group was detected compared to the control group (13.37&#x2009;&#xb1;&#x2009;6.65 vs. 9.44&#x2009;&#xb1;&#x2009;6.55&#x2009;&#x3bc;g/ml; p&#x2009;=&#x2009;0.03). In 11 patients, intraocular anti-aflibercept immunoglobulins could be detected (0.05&#x2009;&#xb1;&#x2009;0.01&#x2009;&#x3bc;g/ml) which was significantly higher than the limit of detection for anti-aflibercept (0.04&#x2009;&#x3bc;g/ml; p&#x2009;=&#x2009;0.001). No correlation was found between the number of injections or the type of CNV and the aqueous level of anti-aflibercept (r&#x2009;=&#x2009;0.02; p&#x2009;=&#x2009;0.95).<br><br>CONCLUSION: According to our results, penetration of non-specific systemic antibodies through the impaired blood-retinal barrier is higher in patients with neovascular AMD than in subjects with an intact structural barrier. Evaluation of neutralizing antibodies to anti-VEGF agents in the aqueous humour can lead us to understanding tachyphylaxis and changes in intraocular immune mechanisms due to AMD.},
}
@article {pmid36627357,
year = {2023},
author = {Philippi, D and Rothaus, K and Castelli, M},
title = {A vision transformer architecture for the automated segmentation of retinal lesions in spectral domain optical coherence tomography images.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {517},
pmid = {36627357},
issn = {2045-2322},
mesh = {Humans ; Angiogenesis Inhibitors/therapeutic use ; Tomography, Optical Coherence/methods ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration/drug therapy ; Retina/diagnostic imaging ; *Retinal Detachment/drug therapy ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is one of the major causes of irreversible blindness and is characterized by accumulations of different lesions inside the retina. AMD biomarkers enable experts to grade the AMD and could be used for therapy prognosis and individualized treatment decisions. In particular, intra-retinal fluid (IRF), sub-retinal fluid (SRF), and pigment epithelium detachment (PED) are prominent biomarkers for grading neovascular AMD. Spectral-domain optical coherence tomography (SD-OCT) revolutionized nAMD early diagnosis by providing cross-sectional images of the retina. Automatic segmentation and quantification of IRF, SRF, and PED in SD-OCT images can be extremely useful for clinical decision-making. Despite the excellent performance of convolutional neural network (CNN)-based methods, the task still presents some challenges due to relevant variations in the location, size, shape, and texture of the lesions. This work adopts a transformer-based method to automatically segment retinal lesion from SD-OCT images and qualitatively and quantitatively evaluate its performance against CNN-based methods. The method combines the efficient long-range feature extraction and aggregation capabilities of Vision Transformers with data-efficient training of CNNs. The proposed method was tested on a private dataset containing 3842 2-dimensional SD-OCT retina images, manually labeled by experts of the Franziskus Eye-Center, Muenster. While one of the competitors presents a better performance in terms of Dice score, the proposed method is significantly less computationally expensive. Thus, future research will focus on the proposed network's architecture to increase its segmentation performance while maintaining its computational efficiency.},
}
@article {pmid36627173,
year = {2024},
author = {Martin-Pinardel, R and Izquierdo-Serra, J and De Zanet, S and Parrado-Carrillo, A and Garay-Aramburu, G and Puzo, M and Arruabarrena, C and Sararols, L and Abraldes, M and Broc, L and Escobar-Barranco, JJ and Figueroa, M and Zapata, MA and Ruiz-Moreno, JM and Moll-Udina, A and Bernal-Morales, C and Alforja, S and Figueras-Roca, M and Gómez-Baldó, L and Ciller, C and Apostolopoulos, S and Mosinska, A and Casaroli Marano, RP and Zarranz-Ventura, J and , },
title = {Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.},
journal = {The British journal of ophthalmology},
volume = {108},
number = {2},
pages = {253-262},
doi = {10.1136/bjo-2022-322297},
pmid = {36627173},
issn = {1468-2079},
mesh = {Humans ; Ranibizumab/therapeutic use ; Angiogenesis Inhibitors/therapeutic use ; Vascular Endothelial Growth Factor A ; Artificial Intelligence ; Tomography, Optical Coherence ; Intravitreal Injections ; *Macula Lutea ; *Retinal Detachment/drug therapy ; *Macular Degeneration/drug therapy ; Subretinal Fluid ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes.<br><br>METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1&#x2009;mm), parafovea (3&#x2009;mm) and perifovea (6&#x2009;mm) were measured in nanoliters (nL) using a validated AI-tool.<br><br>RESULTS: 452 na&#xef;ve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1&#x2009;vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2&#x2009;vs +0.6), parafoveal SRF (+6.9&#x2009;vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4&#x2009;vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4&#x2009;nL, -86.8%), followed by IRF (-17.2&#x2009;nL, -84.7%) and PED (-19.1&#x2009;nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections.<br><br>CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated na&#xef;ve nAMD eyes nationwide.},
}
@article {pmid36626895,
year = {2023},
author = {Kaiser, PK and Giani, A and Fuchs, H and Chong, V and Heier, JS},
title = {Factors That Can Prolong Ocular Treatment Duration in Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {66},
number = {1},
pages = {653-663},
doi = {10.1159/000527815},
pmid = {36626895},
issn = {1423-0259},
mesh = {Humans ; *Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A/metabolism ; Duration of Therapy ; Ranibizumab/therapeutic use ; *Wet Macular Degeneration/drug therapy/metabolism ; Vascular Endothelial Growth Factors/therapeutic use ; Intravitreal Injections ; },
abstract = {Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are used to treat wet age-related macular degeneration (wAMD); however, they are associated with a considerable treatment burden and poor real-world outcomes. The molecular size and charge of anti-VEGF agents influence drug pharmacokinetics in the vitreous and peak drug efficacy. This article reviews the established and novel strategies to prolong drug action, in the vitreal cavity, and thus reduce dosing frequency. Increased ocular residency can be attained by increasing drug size as with large molecules, such as KSI-301; adding polyethylene glycol to pegcetacoplan (APL-2) or avacincaptad pegol to increase molecular size; or binding to other targets that increase molecular size, such as vitreal albumin in the case of BI-X. Faricimab is a bispecific antibody in which the fragment crystallizable portion is engineered to prolong ocular residency and reduce systemic exposure. Conversely, small VEGF-binding molecules, such as brolucizumab, can be administered at higher clinical doses, with the potential for prolonged clinical activity versus larger molecules. Other important considerations include sustained drug delivery routes, such as the ranibizumab port delivery system or subconjunctival or suprachoroidal injection. More effective and longer-lasting treatments are needed for wAMD to prolong drug action and reduce dosing frequency. Several strategies are under investigation and the prevention of vision loss in patients with AMD or other retinal diseases may be attainable in the near future.},
}
@article {pmid36626253,
year = {2023},
author = {Liu, CH and Yemanyi, F and Bora, K and Kushwah, N and Blomfield, AK and Kamenecka, TM and SanGiovanni, JP and Sun, Y and Solt, LA and Chen, J},
title = {Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization.},
journal = {Aging},
volume = {15},
number = {1},
pages = {37-52},
pmid = {36626253},
issn = {1945-4589},
support = {R01 EY029238/EY/NEI NIH HHS/United States ; R01 EY030140/EY/NEI NIH HHS/United States ; R01 EY028100/EY/NEI NIH HHS/United States ; R01 EY024963/EY/NEI NIH HHS/United States ; R01 EY031765/EY/NEI NIH HHS/United States ; },
mesh = {Mice ; Humans ; Animals ; Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A/metabolism ; Visual Acuity ; *Wet Macular Degeneration/complications ; *Choroidal Neovascularization/genetics/drug therapy ; Lasers ; Disease Models, Animal ; Mice, Inbred C57BL ; },
abstract = {Choroidal neovascularization (CNV) causes acute vision loss in neovascular age-related macular degeneration (AMD). Genetic variations of the nuclear receptor RAR-related orphan receptor alpha (RORα) have been linked with neovascular AMD, yet its specific role in pathological CNV development is not entirely clear. In this study, we showed that Rora was highly expressed in the mouse choroid compared with the retina, and genetic loss of RORα in Staggerer mice (Rorasg/sg) led to increased expression levels of Vegfr2 and Tnfa in the choroid and retinal pigment epithelium (RPE) complex. In a mouse model of laser-induced CNV, RORα expression was highly increased in the choroidal/RPE complex post-laser, and loss of RORα in Rorasg/sg eyes significantly worsened CNV with increased lesion size and vascular leakage, associated with increased levels of VEGFR2 and TNFα proteins. Pharmacological inhibition of RORα also worsened CNV. In addition, both genetic deficiency and inhibition of RORα substantially increased vascular growth in isolated mouse choroidal explants ex vivo. RORα inhibition also promoted angiogenic function of human choroidal endothelial cell culture. Together, our results suggest that RORα negatively regulates pathological CNV development in part by modulating angiogenic response of the choroidal endothelium and inflammatory environment in the choroid/RPE complex.},
}
@article {pmid36626211,
year = {2023},
author = {Muste, JC and Russell, MW and Chen, AX and Seth, K and Iyer, AI and Valentim, CCS and Wu, AK and Kuo, BL and Kalur, A and Sastry, R and Hom, GL and Conti, TF and Rich, CA and Talcott, KE and Sharma, S and Singh, RP},
title = {Functional Imaging of Mitochondria in Age-Related Macular Degeneration Using Flavoprotein Fluorescence.},
journal = {Ophthalmic surgery, lasers &amp; imaging retina},
volume = {54},
number = {1},
pages = {24-31},
doi = {10.3928/23258160-20221214-03},
pmid = {36626211},
issn = {2325-8179},
mesh = {Humans ; *Flavoproteins/metabolism ; Angiogenesis Inhibitors ; Visual Acuity ; Vascular Endothelial Growth Factor A ; *Wet Macular Degeneration ; Retina/pathology ; Mitochondria ; Optical Imaging ; },
abstract = {PURPOSE: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD.<br><br>METHODS: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states.<br><br>RESULTS: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity (P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity (P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity (P = 0.018 and 0.024, respectively).<br><br>CONCLUSIONS: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [Ophthalmic Surg Lasers Imaging Retina 2023;54:24-31.].},
}
@article {pmid36626080,
year = {2023},
author = {Akiba, R and Takahashi, M and Baba, T and Mandai, M},
title = {Progress of iPS cell-based transplantation therapy for retinal diseases.},
journal = {Japanese journal of ophthalmology},
volume = {67},
number = {2},
pages = {119-128},
pmid = {36626080},
issn = {1613-2246},
support = {AMED//AMED/ ; },
mesh = {Humans ; *Induced Pluripotent Stem Cells ; *Retinal Diseases/surgery ; Retina ; Retinal Pigment Epithelium ; Cell- and Tissue-Based Therapy ; Cell Transplantation ; *Retinal Degeneration ; },
abstract = {The discovery of induced Pluripotent Stem) (iPS) cells has instigated innovation in various fields, including ophthalmology. Cell therapy has shown tremendous progress in translational research on retinal diseases, including the first-in-human transplantation of autologous iPS cell-derived retinal pigment epithelium (RPE) cells for patients with age-related macular degeneration (AMD). Cell therapy for retinitis pigmentosa (RP) has also been developed. Retinal organoid and photoreceptor cell transplantation has been shown to incorporate into the degenerated host retina, forming synapses with host neurons and resulting in functional recovery. Based on preclinical data, first-in-human transplantation of iPS cell-derived retinal sheets has been conducted. In this review, we summarize the current progress in iPS cell-based retinal cell transplantation research for retinal diseases, addressing some remaining challenges and future prospects.},
}
@article {pmid36622409,
year = {2023},
author = {Dieke, S and Wurche, S and Ruebsam, A and Wirbelauer, C and Joussen, AM and Winterhalter, S},
title = {Impact of intravitreal injection therapy on contrast sensitivity in patients with nAMD and DME.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {261},
number = {7},
pages = {1823-1833},
pmid = {36622409},
issn = {1435-702X},
mesh = {Humans ; Aged ; Angiogenesis Inhibitors ; *Macular Edema/diagnosis/drug therapy/etiology ; *Diabetic Retinopathy/complications/diagnosis/drug therapy ; Vascular Endothelial Growth Factor A ; Contrast Sensitivity ; Intravitreal Injections ; Prospective Studies ; Visual Acuity ; *Wet Macular Degeneration/diagnosis/drug therapy ; },
abstract = {PURPOSE: The study aims to evaluate changes in contrast sensitivity (CS) during therapy with intravitreal vascular endothelial growth factor (VEGF) inhibitors in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).<br><br>METHODS: Prospective, uncontrolled, multicenter study on patients with neovascular AMD or DME who underwent intravitreal injection therapy with Ranibizumab, Aflibercept, or Bevacizumab was conducted. Best corrected visual acuity (BCVA) and CS measured by Mars Letter Contrast Sensitivity Test (MLCS) and Freiburg Visual Acuity and Contrast Test (FrACT) in logCS were evaluated before 3 consecutive VEGF inhibitor injections, which followed the pro renata regimen in treatment-na&#xef;ve and pretreated eyes with a maximum of 9 injections. Correlation of MLCS and FrACT was calculated by the Spearman's rank correlation coefficient.<br><br>RESULTS: Eighty eyes of 74 patients (mean age 72.7; SD&#x2009;&#xb1;&#x2009;9.96) were included. BCVA improved significantly from 0.44 (SD&#x2009;&#xb1;&#x2009;0.21) logMAR to 0.38 (SD&#x2009;&#xb1;&#x2009;0.23) logMAR by 0.06 (SD&#x2009;&#xb1;&#x2009;0.14) logMAR values (p&#x2009;<&#x2009;0.001). CS measured by MLCS increased significantly from 1.27 (SD&#x2009;&#xb1;&#x2009;0.25) logCS to 1.39 (SD&#x2009;&#xb1;&#x2009;0.22) logCS (p&#x2009;<&#x2009;0.001). CS measured by FrACT also improved significantly from 1.22 (SD&#x2009;&#xb1;&#x2009;0.32) logCS to 1.30 (SD&#x2009;&#xb1;&#x2009;0.29) logCS (p&#x2009;=&#x2009;0.035). A positive correlation between MLCS and FrACT was found (r&#x2009;=&#x2009;0.389; p&#x2009;<&#x2009;0.001). Despite statistical significance, results for BCVA, MLCS, and FrACT failed clinical significance. Overall best test results were achieved with MLCS.<br><br>CONCLUSIONS: Intravitreal injection therapy with VEGF inhibitors led to an improvement of BCVA and CS measured by MLCS and FrACT. MLCS was superior and more sensitive compared to FrACT and even BCVA to evaluate CS in elderly patients with macular pathology.},
}
@article {pmid36620704,
year = {2022},
author = {Zartasht Khan, A and Utheim, TP and Eidet, JR},
title = {Retinal Pigment Epithelium Transplantation: Past, Present, and Future.},
journal = {Journal of ophthalmic &amp; vision research},
volume = {17},
number = {4},
pages = {574-580},
pmid = {36620704},
issn = {2008-2010},
abstract = {Retinal pigment epithelium (RPE) is a monolayer of cells situated between photoreceptors and the underlying choroid. It is essential for normal retinal function. Damaged RPE is associated with diseases such as age-related macular degeneration, Stargardt's macular dystrophy, and retinitis pigmentosa. RPE cells can easily be visualized in vivo, sustainable in vitro, and differentiated from stem cells with a relatively straightforward protocol. Due to these properties and the clinical significance of this epithelium in various retinal diseases, RPE transplantation as a treatment modality has gained considerable interest in the last decade. This paper presents the main techniques for RPE transplantation and discusses recent clinically relevant publications.},
}
@article {pmid36620455,
year = {2022},
author = {Wolfrum, P and Fietz, A and Schnichels, S and Hurst, J},
title = {The function of p53 and its role in Alzheimer's and Parkinson's disease compared to age-related macular degeneration.},
journal = {Frontiers in neuroscience},
volume = {16},
number = {},
pages = {1029473},
pmid = {36620455},
issn = {1662-4548},
abstract = {The protein p53 is the main human tumor suppressor. Since its discovery, extensive research has been conducted, which led to the general assumption that the purview of p53 is also essential for additional functions, apart from the prevention of carcinogenesis. In response to cellular stress and DNA damages, p53 constitutes the key point for the induction of various regulatory processes, determining whether the cell induces cell cycle arrest and DNA repair mechanisms or otherwise cell death. As an implication, aberrations from its normal functioning can lead to pathogeneses. To this day, neurodegenerative diseases are considered difficult to treat, which arises from the fact that in general the underlying pathological mechanisms are not well understood. Current research on brain and retina-related neurodegenerative disorders suggests that p53 plays an essential role in the progression of these conditions as well. In this review, we therefore compare the role and similarities of the tumor suppressor protein p53 in the pathogenesis of Alzheimer's (AD) and Parkinson's disease (PD), two of the most prevalent neurological diseases, to the age-related macular degeneration (AMD) which is among the most common forms of retinal degeneration.},
}
@article {pmid36620436,
year = {2022},
author = {Liu, B and He, J and Zhong, L and Huang, L and Gong, B and Hu, J and Qian, H and Yang, Z},
title = {Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula.},
journal = {Frontiers in neuroscience},
volume = {16},
number = {},
pages = {1079498},
pmid = {36620436},
issn = {1662-4548},
abstract = {Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.},
}
@article {pmid36620193,
year = {2022},
author = {Pfeiffer, RL and Jones, BW},
title = {Current perspective on retinal remodeling: Implications for therapeutics.},
journal = {Frontiers in neuroanatomy},
volume = {16},
number = {},
pages = {1099348},
pmid = {36620193},
issn = {1662-5129},
abstract = {The retinal degenerative diseases retinitis pigmentosa and age-related macular degeneration are a leading cause of irreversible vision loss. Both present with progressive photoreceptor degeneration that is further complicated by processes of retinal remodeling. In this perspective, we discuss the current state of the field of retinal remodeling and its implications for vision-restoring therapeutics currently in development. Here, we discuss the challenges and pitfalls retinal remodeling poses for each therapeutic strategy under the premise that understanding the features of retinal remodeling in totality will provide a basic framework with which therapeutics can interface. Additionally, we discuss the potential for approaching therapeutics using a combined strategy of using diffusible molecules in tandem with other vision-restoring therapeutics. We end by discussing the potential of the retina and retinal remodeling as a model system for more broadly understanding the progression of neurodegeneration across the central nervous system.},
}
@article {pmid36618247,
year = {2022},
author = {Serhan, HA and Alma'aitah, HW and Irshaidat, S and Ameer, MA and Asghar, MS and Tahir, MJ},
title = {Ophthalmic manifestations of nutritional deficiencies: A mini review.},
journal = {Journal of family medicine and primary care},
volume = {11},
number = {10},
pages = {5899-5901},
pmid = {36618247},
issn = {2249-4863},
abstract = {Balanced nutrition is crucial for a healthy eye and vision. Many nutritional deficiencies can result in vision impairment. This article reviews the ocular manifestations of vitamin deficiencies, including vitamin A, vitamin B1 and B12, vitamin C, vitamin D, and vitamin E, and minerals such as zinc. It discusses different ophthalmic symptoms and signs, including dry eye disease, corneal xerosis, decreased night vision, subconjunctival hemorrhage, and retinal changes similar to retinitis pigmentosa. We strongly recommend using multi-vitamin supplements for treating many diseases such as age-related macular degeneration.},
}
@article {pmid36617838,
year = {2023},
author = {Wang, Q and He, F and Wu, L},
title = {NLRX1 increases human retinal pigment epithelial autophagy and reduces H2O2-induced oxidative stress and inflammation by suppressing FUNDC1 phosphorylation and NLRP3 activation.},
journal = {Allergologia et immunopathologia},
volume = {51},
number = {1},
pages = {177-186},
pmid = {36617838},
issn = {1578-1267},
mesh = {Humans ; Reactive Oxygen Species/metabolism/pharmacology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Inflammasomes/metabolism/pharmacology ; Hydrogen Peroxide/metabolism/pharmacology ; Retinal Pigment Epithelium/metabolism/pathology ; Phosphorylation ; Interleukin-6/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Oxidative Stress ; *Macular Degeneration/metabolism/pathology ; Carrier Proteins ; Inflammation/pathology ; Autophagy ; Superoxide Dismutase/metabolism/pharmacology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of impaired vision as well as some earlier effects, such as reading and face recognition. Oxidative damage and inflammation of retinal pigment epithelial (RPE) cells are major causes of AMD. Additionally, autophagy in RPE cells can lead to cellular homeostasis under oxidative stress. Nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) is a mysterious modulator of the immune system function which inhibits inflammatory response, attenuates reactive oxygen species (ROS) production, and regulates autophagy. This study attempted to explore the role of NLRX1 in oxidative stress, inflammation, and autophagy in AMD.<br><br>METHODS: An in vitro model of AMD was built in human retinal pigment epithelial cell line 19 (ARPE-19) treated with H2O2. The cell viability, NLRX1 expressions, levels of superoxide dismutase (SOD), glutathione (GHS), and ROS, concentrations of interleukin (IL)-1&#x3b2;, tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), IL-6, and monocyte chemoattractant protein-1 (MCP-1), expressions of NLRX1, p62, LC3-II/LC3-I, FUNDC1, and NOD-like receptor protein 3 (NLRP3) inflammasome were expounded by cell counting kit-8, colorimetric, enzyme-linked immunosorbent serologic assay (ELISA), and Western blot assay.<br><br>RESULTS: H2O2 treatment notably reduced the relative protein expression of NLRX1. Meanwhile, H2O2 incubation decreased cell viability, diminished SOD and GSH concentrations, accompanied with the increased level of ROS, enhanced IL-1&#x3b2;, TNF-&#x3b1;, IL-6, and MCP-1 concentrations, and aggrandized the relative protein expression of p62 with reduced LC3-II/LC3-I ratio. Moreover, these results were further promoted with knockdown of NLRX1 and reversed with overexpression. Mechanically, silencing of NLRX1 further observably enhanced the relative levels of -phosphorylated FUNDC1/FUNDC1, and NLRP3 inflammasome-related proteins, while overexpression of NLRX1 exhibited inverse results in the H2O2-induced ARPE-19 cells.<br><br>CONCLUSION: NLRX1 suppressed H2O2-induced oxidative stress and inflammation, and facilitated autophagy by suppressing FUNDC1 phosphorylation and NLRP3 activation in ARPE-19 cells.},
}
@article {pmid36617586,
year = {2023},
author = {Wei, W and Mazzola, M and Otero-Marquez, O and Tong, Y and Souied, E and Querques, G and Bailey Freund, K and Theodore Smith, R},
title = {Two potentially distinct pathways to geographic atrophy in age-related macular degeneration characterized by quantitative fundus autofluorescence.},
journal = {Eye (London, England)},
volume = {37},
number = {11},
pages = {2281-2288},
pmid = {36617586},
issn = {1476-5454},
support = {R01 EY015520/EY/NEI NIH HHS/United States ; R01 EY015520/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Geographic Atrophy/diagnosis ; *Macular Degeneration/diagnosis/pathology ; *Retinal Drusen/diagnosis/pathology ; Fundus Oculi ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Retinal Pigment Epithelium/pathology ; },
abstract = {BACKGROUND/AIMS: To demonstrate two distinct pathways to geographic atrophy (GA) that originate from soft drusen/ pigment epithelial detachments (PEDs) and subretinal drusenoid deposits (SDDs), respectively, and are characterized by their final quantitative autofluorescence (qAF) levels.<br><br>METHODS: 23 eyes of 18 patients with GA underwent spectral-domain optical coherence tomography (SD-OCT) and qAF imaging on the qAF-ready Heidelberg Spectralis. 52 GA Regions-of-interest (ROIs), or clusters of adjacent lesions, were selected, and the ROIs were divided into groups by the dominant iAMD precursors on prior serial tracked SD-OCT scans. Mean qAF values and structural SD-OCT findings of groups were compared.<br><br>RESULTS: Group 1 lesions (soft drusen/PED precursors, 18/52) were isolated, with lower mean qAF (35.88&#x2009;&#xb1;&#x2009;12.75 units); group 3 lesions (SDD precursors, 12/52) were multilobular, with significantly higher mean qAF (71.62&#x2009;&#xb1;&#x2009;12.12 units, p&#x2009;<&#x2009;0.05). Group 2 lesions, (mixed precursors, 22/52) had intermediate mean qAF (58.13&#x2009;&#xb1;&#x2009;67.92 units). Significantly greater prevalence of split RPE/ Bruch's membrane complex in SDD-associated GA, suggesting basal laminar deposit (BLamD), than in drusen-associated lesions was the major structural difference.<br><br>CONCLUSION: Quantitative autofluorescence (qAF) of GA lesions may reflect two distinct pathogenic pathways and structural outcomes, originating from soft drusen/PED and subretinal drusenoid deposits (SDDs), with the final qAF values lower or higher, respectively. Basal laminar deposit specifically in and adjacent to SDD-associated lesions may account for their greater autofluorescence. The potential importance of this paradigm is that it could direct, simplify and facilitate research on geographic atrophy by dividing the disease into two components that may be studied separately.},
}
@article {pmid36617346,
year = {2023},
author = {Liu, K and Li, H and Wang, F and Su, Y},
title = {Ferroptosis: mechanisms and advances in ocular diseases.},
journal = {Molecular and cellular biochemistry},
volume = {478},
number = {9},
pages = {2081-2095},
pmid = {36617346},
issn = {1573-4919},
mesh = {Humans ; *Ferroptosis ; Reactive Oxygen Species ; Retina ; Iron ; *Retinal Neoplasms ; Lipid Peroxidation ; },
abstract = {As an essential trace element in the body, iron is critical for the maintenance of organismal metabolism. Excessive iron facilitates reactive oxygen species generation and inflicts damage on cells and tissues. Ferroptosis, a newly identified iron-dependent type of programmed cell death, has been implicated in a broad set of metabolic disorders. Ferroptosis is mainly characterized by excess iron accumulation, elevated lipid peroxides and reactive oxygen species, and reduced levels of glutathione and glutathione peroxidase 4. The vast emerging literature on ferroptosis has shown that numerous diseases, such as cancers, neurodegeneration, and autoimmune diseases, are associated with ferroptosis. Meanwhile, recent studies have confirmed the relationship between ferroptosis and eye diseases including keratopathy, cataract, glaucoma, retinal ischemia-reperfusion injury, age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and retinoblastoma, indicating the critical role of ferroptosis in ocular diseases. In this article, we introduce the primary signaling pathways of ferroptosis and review current advances in research on ocular diseases involving iron overload and ferroptosis. Furthermore, several unanswered questions in the area are raised. Addressing these unanswered questions promises to provide new insights into preventing, controlling, and treating not only ocular diseases but also a variety of other diseases in the near future.},
}
@article {pmid36617234,
year = {2023},
author = {Ogawa, K and Urata, K and Suzuki, Y and Sugamoto, K and Goto, Y and Nakayama, T and Nishiyama, K and Kunitake, H and Yamasaki, M},
title = {Blueberry stem extract and stem active components prevent blue light-emitting diode light-induced retinal photoreceptor cell damage in vitro.},
journal = {Bioscience, biotechnology, and biochemistry},
volume = {87},
number = {4},
pages = {378-388},
doi = {10.1093/bbb/zbad001},
pmid = {36617234},
issn = {1347-6947},
mesh = {*Blueberry Plants/metabolism ; Reactive Oxygen Species/metabolism ; Retina ; Apoptosis ; Photoreceptor Cells, Vertebrate/metabolism ; Light ; Plant Extracts/pharmacology/metabolism ; },
abstract = {Blue light causes retinal damage that can lead to ocular diseases such as age-related macular degeneration. In this study, we determined the protective effect of blueberry stem extract (BStEx) and active components on blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage in vitro. Photoreceptor cells cultured in the presence of BStEx or components were exposed to blue light to induce cell damage. BStEx, fractions of BStEx containing proanthocyanidins, chlorogenic acid, catechin, and epicatechin prevented the cell damage and/or inhibited the generation of reactive oxygen species (ROS). Furthermore, BStEx reduced apoptosis and cell death, and inhibited the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase leading to cellular apoptosis induced by blue light exposure. These findings suggest that BStEx and components exert a protective effect against blue light-induced photoreceptor cell damage through the inhibition of MAPK phosphorylation and ROS production.},
}
@article {pmid36615095,
year = {2022},
author = {Wąsowska, A and Teper, S and Matczyńska, E and Łyszkiewicz, P and Sendecki, A and Machalińska, A and Wylęgała, E and Boguszewska-Chachulska, A},
title = {Polygenic Risk Score Impact on Susceptibility to Age-Related Macular Degeneration in Polish Patients.},
journal = {Journal of clinical medicine},
volume = {12},
number = {1},
pages = {},
pmid = {36615095},
issn = {2077-0383},
abstract = {Age-related macular degeneration (AMD) is a common retina degenerative disease with a complex genetic and environmental background. This study aimed to determine the polygenic risk score (PRS) stratification between the AMD case and control patients. The PRS model was established on the targeted sequencing data of a cohort of 471 patients diagnosed with AMD and 167 healthy controls without symptoms of retinal degeneration. The highest predictive value to the target dataset was achieved for a 22-variant model with a p-value lower than threshold PT = 0.0123. The median PRS for cases was higher by 1.1 than for control samples (95% CI: (−1.19; −0.85)). The patients in the highest quantile had a significantly higher relative risk of developing AMD than those in the lowest reference quantile (OR = 35.13, 95% CI: (7.9; 156.1), p < 0.001). The diagnostic ability was investigated using ROC analysis with AUC = 0.76 (95% CI: (0.72; 0.80)). The polygenic susceptibility to AMD may be the starting point to expand AMD diagnostics based on rare highly penetrant variants and investigate associations with disease progression and treatment response in Polish patients in future studies.},
}
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